CN104193767B - A kind of cefamandole nafate superfine powder preparation and preparation method thereof - Google Patents
A kind of cefamandole nafate superfine powder preparation and preparation method thereof Download PDFInfo
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- CN104193767B CN104193767B CN201410385066.7A CN201410385066A CN104193767B CN 104193767 B CN104193767 B CN 104193767B CN 201410385066 A CN201410385066 A CN 201410385066A CN 104193767 B CN104193767 B CN 104193767B
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- cefamandole nafate
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- 238000002360 preparation method Methods 0.000 title claims abstract description 31
- RRJHESVQVSRQEX-SUYBPPKGSA-N O-formylcefamandole Chemical compound CN1N=NN=C1SCC1=C(C(O)=O)N2C(=O)[C@@H](NC(=O)[C@H](OC=O)C=3C=CC=CC=3)[C@H]2SC1 RRJHESVQVSRQEX-SUYBPPKGSA-N 0.000 title claims abstract description 29
- 229960002440 cefamandole nafate Drugs 0.000 title claims abstract description 29
- 239000000843 powder Substances 0.000 title claims abstract description 23
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 27
- 150000001875 compounds Chemical class 0.000 claims abstract description 26
- 238000006243 chemical reaction Methods 0.000 claims abstract description 18
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims abstract description 16
- ICZOIXFFVKYXOM-YCLOEFEOSA-M cefamandole nafate Chemical compound [Na+].CN1N=NN=C1SCC1=C(C([O-])=O)N2C(=O)[C@@H](NC(=O)[C@H](OC=O)C=3C=CC=CC=3)[C@H]2SC1 ICZOIXFFVKYXOM-YCLOEFEOSA-M 0.000 claims abstract description 10
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims abstract description 8
- 238000000034 method Methods 0.000 claims abstract description 7
- HXUIDZOMTRMIOE-UHFFFAOYSA-N 3-oxo-3-phenylpropionic acid Chemical compound OC(=O)CC(=O)C1=CC=CC=C1 HXUIDZOMTRMIOE-UHFFFAOYSA-N 0.000 claims abstract description 4
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims abstract description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims abstract description 4
- 235000019253 formic acid Nutrition 0.000 claims abstract description 4
- 239000002245 particle Substances 0.000 claims abstract description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 claims abstract description 4
- 239000012279 sodium borohydride Substances 0.000 claims abstract description 4
- 159000000000 sodium salts Chemical class 0.000 claims abstract description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 14
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- 239000012046 mixed solvent Substances 0.000 claims description 5
- 230000032050 esterification Effects 0.000 claims description 4
- 238000005886 esterification reaction Methods 0.000 claims description 4
- 238000001953 recrystallisation Methods 0.000 claims description 4
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims description 3
- 239000003054 catalyst Substances 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 238000004806 packaging method and process Methods 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- FZEVMBJWXHDLDB-ZCFIWIBFSA-N (6r)-5-thia-1-azabicyclo[4.2.0]oct-2-en-8-one Chemical compound S1CC=CN2C(=O)C[C@H]21 FZEVMBJWXHDLDB-ZCFIWIBFSA-N 0.000 claims 2
- 150000001735 carboxylic acids Chemical class 0.000 claims 2
- -1 methyl 1H tetrazolium Chemical compound 0.000 claims 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 2
- AYDQIZKZTQHYIY-UHFFFAOYSA-N OC(=O)C1(C)CC(C(O)=O)=CC=C1 Chemical compound OC(=O)C1(C)CC(C(O)=O)=CC=C1 AYDQIZKZTQHYIY-UHFFFAOYSA-N 0.000 abstract description 5
- 238000010923 batch production Methods 0.000 abstract description 2
- 230000009286 beneficial effect Effects 0.000 abstract description 2
- 238000010276 construction Methods 0.000 abstract description 2
- 239000004035 construction material Substances 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- 239000000047 product Substances 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical group Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
- 229930186147 Cephalosporin Natural products 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 229940124587 cephalosporin Drugs 0.000 description 2
- 150000001780 cephalosporins Chemical class 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- LSBDFXRDZJMBSC-UHFFFAOYSA-N Amide-Phenylacetic acid Natural products NC(=O)CC1=CC=CC=C1 LSBDFXRDZJMBSC-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010061695 Biliary tract infection Diseases 0.000 description 1
- 206010022678 Intestinal infections Diseases 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 210000003445 biliary tract Anatomy 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 208000003167 cholangitis Diseases 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 1
- 206010034674 peritonitis Diseases 0.000 description 1
- 210000003800 pharynx Anatomy 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 208000013223 septicemia Diseases 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
- 210000002229 urogenital system Anatomy 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- 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
- 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
- C07D501/24—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with hydrocarbon radicals, substituted by hetero atoms or hetero rings, attached in position 3
- C07D501/36—Methylene radicals, substituted by sulfur atoms
-
- 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
- C07D501/02—Preparation
- C07D501/04—Preparation from compounds already containing the ring or condensed ring systems, e.g. by dehydrogenation of the ring, by introduction, elimination or modification of substituents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Cephalosporin Compounds (AREA)
Abstract
The preparation method of a kind of cefamandole nafate superfine powder preparation of disclosure: (1), reacted with thionyl chloride by benzoyl acetic acid, thionyl chloride is removed after terminating by reaction；(2), the product obtained is dissolved in dichloromethane, is then added thereto to 7-amino-3-[(1-methyl isophthalic acid H-tetrazolium-5-base) sulfidomethyl]-3-cephem-4-carboxylic acid again, after reaction, obtains compound (I)；(3), compound (I) is dissolved in oxolane, then wherein to entering sodium borohydride, after reaction, obtains compound (II): (4), compound (II) and formic acid are obtained by reacting compound Mandokef；(5), sodium salt is made；(6), dried comminution by gas stream become superfine powder, the particle diameter of superfine powder is 0.5 ~ 3 μm.This method simple in construction, and raw material is cheap, is beneficial to batch production.
Description
Technical field
The preparation method that the present invention relates to a kind of cefamandole nafate superfine powder preparation.
Background technology
Cefamandole nafate belongs to second generation cephalosporin class antibiotic, this product is the second generation cephalosporin class antibiotic succeeded in developing by Lilly company of the U.S. at first, and clinical practice is in the respiratory tract caused by sensitive gram-negative bacteria, genito-urinary system, skin and soft tissue, bone and site infection and peritonitis, the septicemia etc. such as joint, pharynx otorhinolaryngology.Biliary tract and intestinal infection there is good therapeutic effect.
Cefamandole nafate was applied to clinic in 1978, commodity are called Mandol, chemistry 7-D-(2-methanoyl phenyl acetamide)-3-[(1-methyl isophthalic acid H-tetrazolium-5 base) sulfidomethyl]-3-cephem-4-carboxylic acid sodium salt by name, molecular weight is 512.50, its structural formula shown in formula I:
Formula 1
The synthetic method of cefamandole nafate of the prior art all can effectively prepare cefamandole nafate, but the purity of target product is not high, and colour-difference, content is low.Method complicated operation, later stage process the reasons such as loaded down with trivial details simultaneously, are subject to bigger restriction in big production.
Summary of the invention
Due to the disadvantages mentioned above of prior art, the present invention proposes a kind of cefamandole nafate superfine powder preparation and preparation method thereof, and it can effectively solve the disadvantages mentioned above of prior art.
The present invention is by the following technical solutions:
A kind of preparation method of cefamandole nafate superfine powder preparation:
(1), being reacted with thionyl chloride by benzoyl acetic acid, thionyl chloride is removed after terminating by reaction；
(2), the product obtained in step (1) is dissolved in dichloromethane, then 7-amino-3-[(1-methyl isophthalic acid H-tetrazolium-5-base) sulfidomethyl]-3-cephem-4-carboxylic acid it is added thereto to again, obtaining compound (I) after reaction, compound (I) structure is as follows:
(3), being dissolved in oxolane by compound (I), then wherein to entering sodium borohydride, obtain compound (II) after reaction, the structure of compound (II) is as follows:
(4), compound (II) and formic acid esterification are obtained by reacting compound Mandokef；
(5), Mandokef is made sodium salt；
(6), with comminution by gas stream, cefamandole nafate being become superfine powder after drying, reclaim, packaging, the particle diameter of superfine powder is 0.5 ~ 3 μm.
In step (1), the condition of reaction is for being stirred at room temperature.
Comminution by gas stream in described step (6) adopts multi-stage crushing method, and air velocity is 350 ~ 450m/s.
In described step (2), the condition of reaction is for being stirred at room temperature, and the mol ratio of the product obtained in step (1) and 7-amino-3-[(1-methyl isophthalic acid H-tetrazolium-5-base) sulfidomethyl]-3-cephem-4-carboxylic acid is 1:1.5.
The product obtained in step (2) is passed through the mixed solvent recrystallization of ethanol and dichloromethane, obtains the monocrystalline of compound (I).
In step (4), the solvent used by esterification is ethyl acetate, and catalyst is 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride.
The product obtained in described step (2) is by the mixed solvent recrystallization of ethanol that volume ratio is 10:11 with dichloromethane.
A kind of preparation of the cefamandole nafate superfine powder prepared containing above-mentioned preparation method.
The invention have the advantages that this method simple in construction, and raw material is cheap, is beneficial to batch production.
Detailed description of the invention:
Below in conjunction with detailed description of the invention, the present invention is described in detail.Should be understood that these embodiments are merely to illustrate the present invention rather than restriction the scope of the present invention.In addition, it is to be understood that after having read the content that the present invention lectures, the present invention can be made various changes or modifications by those skilled in the art, and these equivalent form of values fall within the application appended claims limited range equally.
Embodiment 1:
Being dissolved in the thionyl chloride of 5mL by the benzoyl acetic acid of 1mol, reaction is stirred at room temperature, thionyl chloride evaporation is removed after terminating by reaction；The product obtained is dissolved in dichloromethane, is then added thereto to 7-amino-3-[(1-methyl isophthalic acid H-tetrazolium-5-base) the sulfidomethyl]-3-cephem-4-carboxylic acid of 1.5mol again, after reaction, obtains compound (I)；Compound (I) is dissolved in oxolane, then wherein to entering sodium borohydride under condition of ice bath, compound (II) is obtained after reaction, by compound (II) heating for dissolving in ethanol and methylene chloride volume ratio in the mixed solvent of 10:11, the crystal of cooling precipitation compounds (II)；Compound (II) is dissolved in ethyl acetate, then 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride of catalytic amount and the formic acid of 1.5mol it are added thereto to, it is heated to reflux 12h, it is obtained by reacting compound Mandokef, the product being obtained by reacting is purified by column chromatography the Mandokef obtaining sterling；Then Mandokef is dissolved in ethanol and the acetone of 5mL1:1, then sodium acetate it is added thereto to, reaction is stirred at room temperature to there being crystallization, filtering product, and with the ethanol of 1:1 and washing with acetone filter cake, product is vacuum drying under 40 degree, obtains cefamandole nafate 315g, by comminution by gas stream, the cefamandole nafate obtained is adopted multi-stage crushing method, and air velocity is 350 ~ 450m/s superfine powder preparing that particle diameter is 0.5 ~ 3 μm.
Embodiment 2
The sample that will prepare in embodiment 1, add water the solution made in every 1mL containing cefamandole nafate 20 μ g, measuring according to spectrophotography (China's coastal port two), result has absorption maximum, result to meet the ultraviolet spectrum characteristic of cefamandole nafate at the wavelength place of 269nm.
Embodiment 3
Adopting filler is the chromatographic column of octadecylsilane chemically bonded silica, with acetonitrile-10% triethylamine (with phosphorus acid for adjusting pH value to 2.5) (20:80) for mobile phase, detection wavelength is 254nm, the cefamandole nafate prepared in embodiment 1 is added water and makes every 1mL solution containing cefamandole nafate 0.5mg, as test sample, the cefamandole nafate taking listing makes the solution of same concentrations, is then injected into chromatograph, record retention time, result shows that retention time is consistent.
Result of implementation shows, the sample in embodiment 1 measures through HPLC and shows that it is consistent with the reference substance of cefamandole nafate.
Embodiment 4
The Mandokef superfine powder prepared in embodiment 1 is made preparation.
Should be understood that these embodiments are merely to illustrate the present invention rather than restriction the scope of the present invention.In addition, it is to be understood that after having read the content that the present invention lectures, the formula of the present invention can be made various changes or modifications by those skilled in the art, and these equivalent form of values fall within the application appended claims limited range equally.
Claims (8)
1. the preparation method of a cefamandole nafate superfine powder preparation, it is characterised in that:
(1), being reacted with thionyl chloride by benzoyl acetic acid, thionyl chloride is removed after terminating by reaction；
(2), the product obtained in step (1) is dissolved in dichloromethane, then it is added thereto to 7 amino 3 [(1 methyl 1H tetrazolium 5 base) sulfidomethyl] 3 cephem 4 carboxylic acids again, after reaction, obtains compound (I)；
(3), compound (I) is dissolved in oxolane, then wherein to entering sodium borohydride, after reaction, obtains compound (II)；
(4), compound (II) and formic acid esterification are obtained by reacting compound Mandokef；
(5), Mandokef is made sodium salt；
(6), with comminution by gas stream, cefamandole nafate being become superfine powder after drying, reclaim, packaging, the particle diameter of superfine powder is 0.5～3 μm.
2. the preparation method of cefamandole nafate superfine powder preparation according to claim 1, it is characterised in that: in step (1), the condition of reaction is for being stirred at room temperature.
3. the preparation method of cefamandole nafate superfine powder preparation according to claim 2, it is characterised in that: the comminution by gas stream in described step (6) adopts multi-stage crushing method, and air velocity is 350～450m/s.
4. the preparation method of cefamandole nafate superfine powder preparation according to claim 3, it is characterized in that: in described step (2), the condition of reaction is for being stirred at room temperature, and the mol ratio of the product obtained in step (1) and 7 amino 3 [(1 methyl 1H tetrazolium 5 base) sulfidomethyl] 3 cephem 4 carboxylic acids is 1:1.5.
5. the preparation method of cefamandole nafate superfine powder preparation according to claim 4, it is characterized in that: the product obtained in step (2) is passed through the mixed solvent recrystallization of ethanol and dichloromethane, obtains the monocrystalline of compound (I).
6. the preparation method of cefamandole nafate superfine powder preparation according to claim 5, it is characterized in that: in step (4), solvent used by esterification is ethyl acetate, and catalyst is 1 ethyl (3 dimethylaminopropyl) carbodiimide hydrochloride.
7. the preparation method of cefamandole nafate superfine powder preparation according to claim 6, it is characterised in that: the product obtained in described step (2) is by the mixed solvent recrystallization of ethanol that volume ratio is 10:11 with dichloromethane.
8. the preparation of the cefamandole nafate superfine powder prepared containing, for example the preparation method described in any one in claim 1 to 7.
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| CN201410385066.7A CN104193767B (en) | 2014-08-07 | 2014-08-07 | A kind of cefamandole nafate superfine powder preparation and preparation method thereof |
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| CN201410385066.7A CN104193767B (en) | 2014-08-07 | 2014-08-07 | A kind of cefamandole nafate superfine powder preparation and preparation method thereof |
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| CN104193767B true CN104193767B (en) | 2016-07-06 |
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Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3641021A (en) * | 1969-04-18 | 1972-02-08 | Lilly Co Eli | 3 7-(ring-substituted) cephalosporin compounds |
| US3928334A (en) * | 1974-06-06 | 1975-12-23 | Bristol Myers Co | Process for the production of cefamandole |
| JPS5390285A (en) * | 1977-01-17 | 1978-08-08 | Sankyo Co Ltd | Preparation of cephalosporin derivs. |
| EP0029202B1 (en) * | 1979-11-16 | 1983-04-13 | Asahi Kasei Kogyo Kabushiki Kaisha | Novel tetrazole-5-thiol esters and process for preparing cefamandole using same |
| CN100554271C (en) * | 2007-07-27 | 2009-10-28 | 苏州中联化学制药有限公司 | Method for synthesizing antibiotic cefamandole nafate |
| CN101475580B (en) * | 2009-01-21 | 2010-08-18 | 海南美大制药有限公司 | Cefamandole nafate compounds synthesizing method |
| CN102276629A (en) * | 2011-08-22 | 2011-12-14 | 苏州二叶制药有限公司 | Synthetic route for cefamandole nanfate |
| WO2013057197A1 (en) * | 2011-10-20 | 2013-04-25 | Dsm Sinochem Pharmaceuticals Netherlands B.V. | Process for the formylation of cefamandole |
| WO2013057196A1 (en) * | 2011-10-20 | 2013-04-25 | Dsm Sinochem Pharmaceuticals Netherlands B.V. | Process for the preparation of cefamandole nafate |
| CN102372728B (en) * | 2011-11-28 | 2013-12-11 | 齐鲁安替制药有限公司 | Synthesizing method for cephalosporin compound |
| CN102816172A (en) * | 2012-08-17 | 2012-12-12 | 苏州中联化学制药有限公司 | Preparation process of cefamandole nafate |
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Inventor after: Fu Miaoqing Inventor after: Li Fengsheng Inventor after: Chen Yudong Inventor before: Fu Miaoqing Inventor before: Li Fengsheng Inventor before: Chen Zongdong |
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Effective date of registration: 20200409 Address after: 310000 room 1301 and 1401, building B, No. 3, Weiye Road, Binjiang District, Hangzhou City, Zhejiang Province Patentee after: ZHEJIANG CHANGDIAN PHARMACEUTICAL Co.,Ltd. Address before: Room 701, building 2, Tongce Plaza, 3688 Jiangnan Avenue, Binjiang District, Hangzhou City, Zhejiang Province Patentee before: HANGZHOU CHANGDIAN MEDICAL TECHNOLOGY Co.,Ltd. |
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Denomination of invention: The invention relates to an ultra-fine powder preparation of cefmendole axetil sodium and a preparation method thereof Effective date of registration: 20210325 Granted publication date: 20160706 Pledgee: China Minsheng Banking Corp Hangzhou branch Pledgor: ZHEJIANG CHANGDIAN PHARMACEUTICAL Co.,Ltd. Registration number: Y2021330000241 |
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Granted publication date: 20160706 Pledgee: China Minsheng Banking Corp Hangzhou branch Pledgor: ZHEJIANG CHANGDIAN PHARMACEUTICAL CO.,LTD. Registration number: Y2021330000241 |
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