CN109384800A - A kind of preparation method of cefotiam hydrochloride - Google Patents
A kind of preparation method of cefotiam hydrochloride Download PDFInfo
- Publication number
- CN109384800A CN109384800A CN201811385439.5A CN201811385439A CN109384800A CN 109384800 A CN109384800 A CN 109384800A CN 201811385439 A CN201811385439 A CN 201811385439A CN 109384800 A CN109384800 A CN 109384800A
- Authority
- CN
- China
- Prior art keywords
- cefotiam hydrochloride
- preparation
- nitrogen
- ethyl acetate
- hours
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
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
- C07D501/12—Separation; Purification
Abstract
The invention belongs to pharmaceutical technology fields, disclose a kind of preparation method of cefotiam hydrochloride.This method dissolves cefotiam hydrochloride crude product using water for injection, antioxidant sodium sulfite-EDTA is added, add active carbon decoloring, except heat source, then re-crystallizing in ethyl acetate is added, the nitrogen that gained crystal is passed through specific temperature is dry, obtains moisture and organic residue is low, with high purity, stability is strong cefotiam hydrochloride crystal powder.
Description
Technical field
The invention belongs to pharmaceutical technology fields, and in particular to a kind of preparation method of cefotiam hydrochloride.
Background technique
Cefotiam hydrochloride, English name: cefotiam hydrochloride, chemical name: (6R, 7R) -7- [[(2-
Amino -4- thiazolyl) acetyl group] amino] -3- [[1- [2- (dimethylamino) ethyl] -1H-TETRAZOLE -5- base] sulphomethyl] -8-
Oxo -5- thia -1- azabicyclo [4.2.0] oct-2-ene -2- carboxylic acid dihydrochloride.Chemical structural formula is as follows:
Molecular formula: C18H23N9O4S3·2HCl
Molecular weight: 598.56
Cefotiam is researched and developed by Japanese Wu Tian company, and 1981 for the first time in the semi-synthetic cephalo bacterium of the second generation of Japan's listing
Element.This product is close to the effect of gram positive bacteria and cephazoline (cefazolin), to gram-negative bacteria, such as haemophilus, greatly
The effects of uncommon bacterium of intestines angstrom, klebsiella spp, proteus mirabilis, is more excellent, to enterobacteria, citrobacter, indole-positive deformed rod
Bacterium etc. also has antibacterial action.The dihydrochloride intravenous injection administration of clinical use is mainly used for infection caused by treating sensitive bacteria,
The infection as caused by pneumonia, bronchitis, infection of biliary tract, peritonitis, urinary tract infections and operation and wound and septicemia etc..
Since cefotiam hydrochloride is in storing process, water content and Determination of Residual Solvents are excessively high, will cause drug hydrolysis, oxygen
Change, so that effective ingredient content reduces, bad stability, polymeric impurities content is increased, and so that human body is generated allergy anti-
It answers.In addition under conditions of high temperature (50 DEG C of >), degradation and poly- cooperative response are tended to occur, will also result in polymer content raising.
Patent CN102746324A provides the purification process and cefotiam hydrochloride sterile powder injection of a kind of cefotiam hydrochloride.The party
Water dissolve salt that injection active carbon is added in sour Cefotiam sodium crude product removes heat source for method, and acetone is then added and is recrystallized, gained
After ether or methyl tertiary butyl ether(MTBE) are washed and starched, filtering is filtered through water flowing saturation nitrogen crystal again, is obtained after being dried under reduced pressure low organic
Remaining Cefotiam aseptic powder.
Patent CN103159787A provides a kind of preparation method of sterile cefotiam hydrochloride of high-purity.This method includes
By cefotiam hydrochloride crude product by multistep recrystallization and washing process, and use dehydrated alcohol as recrystallisation solvent.
Patent CN101787037B provides a kind of cefotiam hydrochloride compound, by specially designed acid-base chemical conversion and
The method of macroporous absorbent resin absorption, achievees the purpose that polishing purification.
Patent CN103601737B provides a kind of preparation method of cefotiam hydrochloride.This method passes through to reaction process
The mother liquor that middle cefotiam hydrochloride crude product and purification two-step reaction generate is handled, and processing post mother liquor is recycled respectively and salt
During sour Cefotiam crude product synthesis and purification two-step reaction, so that cefotiam hydrochloride product yield greatly improves.
The water content of above-mentioned patent and in the prior art cefotiam hydrochloride is not paid attention to, still to finished product stability
There is larger impact, polymeric impurities content is be easy to cause to be sharply increased.Lower in order to obtain a kind of water content, performance is more stable
Cefotiam hydrochloride compound, the present invention is specifically proposed.
Summary of the invention
The object of the present invention is to provide a kind of preparation methods of cefotiam hydrochloride.This method is using specific drying side
Formula is dried with nitrogen high-purity hydrochloric acid Cefotiam crystal using temperature control, reduces solvent residual and water content, optimizes technique ginseng
Number, shortens arid cycle, to obtain that water content is low, Residual organic solvent is low, the Cefotiam of apyrogeneity, purity is high is sterile
Powder.
In order to achieve the object of the present invention, this invention takes following technical solutions:
A kind of preparation method of cefotiam hydrochloride, it is characterised in that the following steps are included:
(1) cefotiam hydrochloride crude product is added in treatment tank, is dissolved with water for injection, adds antioxidant, dissolved clarification, enriching
Hydrochloric acid is adjusted to strong acidic environment, is added ethyl acetate, then plus active carbon decoloring, filtering;
(2) filtrate is transferred in crystallization apparatus, quickly stirs, and adds ethyl acetate, formation supersaturation stirring while adding
Liquid is cooled to 14 DEG C, and crystal seed is added, adds ethyl acetate, then be cooled to 0-5 DEG C of growing the grain 0.5-3 hours, is transferred to three-in-one;
(3) it filters, ethyl acetate washing is passed through 15-25 DEG C of nitrogen predrying 0.1-3 hours, later on stirring, by nitrogen
It is 0.5-4 hours dry that gas is warming up to 25-55 DEG C, then to continue to be passed through the dry 0.5-5 of nitrogen after material is warming up to 30-50 DEG C small
When, discharging stirring, is crushed, is dispensed to get finished product.
Preferably, nitrogen predrying includes: to be passed through 18-24 DEG C of nitrogen 0.5-1 hours in step (3), and drying can extremely stir
State.
Preferably, in step (3) nitrogen temperature to 30-40 DEG C it is 1-3 hours dry.
Preferably, material continues to be passed through nitrogen drying 1-4 hours after being warming up to 35-45 DEG C in step (3).
Preferably, it dries in step (3) to water content≤3%.
Preferably, antioxidant described in step (1) is sodium sulfite-EDTA, and dosage is the 0.1- of crude product weight
0.5%, more preferably, sodium sulfite-EDTA dosage is the 0.2% of crude product weight.
Preferably, strong acidic environment PH described in step (1) is 0.1-1.0.
Preferably, 2-5 times that ethyl acetate weight is crude product weight is added in step (1).
Preferably, rearing crystal time is 1-2 hours in step (2)
Purification process provided by the invention dissolves cefotiam hydrochloride crude product using water for injection, and antioxidant sulfurous is added
Sour sodium-EDTA adds active carbon decoloring, except heat source, re-crystallizing in ethyl acetate is then added, gained crystal is passed through the nitrogen of specific temperature
Gas is dry.The present invention uses specific drying mode, shortens arid cycle, moisture and solvent residual is reduced, to obtain purity
Cefotiam hydrochloride crystal powder high, stability is strong.
Specific embodiment
With embodiment, further description of the technical solution of the present invention below, it will help to technical solution of the present invention
The advantages of, effect have and further understand, the scope of protection of the present invention is not limited for embodiment, and protection scope of the present invention is by weighing
Benefit requires to determine.
Embodiment 1:
The preparation of cefotiam hydrochloride:
(1) cefotiam hydrochloride crude product 90kg is added in treatment tank, is dissolved with water for injection, adds 90g sodium sulfite-
EDTA, dissolved clarification.It is 0.8 that enriching hydrochloric acid, which is adjusted to PH, adds 280L ethyl acetate.Active carbon decoloring, filtering is added.
(2) filtrate is transferred in crystallization apparatus, quickly stirs, and adds ethyl acetate, formation supersaturation stirring while adding
Liquid is cooled to 14 DEG C, and crystal seed is added, adds ethyl acetate 2000L, then be cooled to 0-5 DEG C of growing the grain 1 hour, is transferred to three-in-one;
(3) it filters, ethyl acetate washing is passed through 23 DEG C of nitrogen predryings 0.5 hour, later on stirring, by nitrogen liter
Temperature to 30 DEG C it is 1 hour dry, then material is warming up to after 35 DEG C to continue to be passed through nitrogen 1 hour dry, discharging, stirring, crush, point
Dress is to get finished product.
Embodiment 2:
The preparation of cefotiam hydrochloride:
(1) cefotiam hydrochloride crude product 90kg is added in treatment tank, is dissolved with water for injection, adds 270g sodium sulfite-
EDTA, dissolved clarification.It is 0.2 that enriching hydrochloric acid, which is adjusted to PH, adds 500L ethyl acetate.Active carbon decoloring, filtering is added.
(2) filtrate is transferred in crystallization apparatus, quickly stirs, and adds ethyl acetate, formation supersaturation stirring while adding
Liquid is cooled to 14 DEG C, and crystal seed is added, adds ethyl acetate 3000L, then be cooled to 0-5 DEG C of growing the grain 2 hours, is transferred to three-in-one;
(3) it filters, ethyl acetate washing is passed through 22 DEG C of nitrogen predryings 1 hour, later on stirring, by nitrogen temperature
It is 2 hours dry to 34 DEG C, then material is warming up to after 45 DEG C to continue to be passed through nitrogen 1.5 hours dry, discharging, stirring, crush, point
Dress is to get finished product.
Embodiment 3:
The preparation of cefotiam hydrochloride:
(1) cefotiam hydrochloride crude product 90kg is added in treatment tank, is dissolved with water for injection, adds 230g sodium sulfite-
EDTA, dissolved clarification.It is 0.6 that enriching hydrochloric acid, which is adjusted to PH, adds 400L ethyl acetate.Active carbon decoloring, filtering is added.
(2) filtrate is transferred in crystallization apparatus, quickly stirs, and adds ethyl acetate, formation supersaturation stirring while adding
Liquid is cooled to 14 DEG C, and crystal seed is added, adds ethyl acetate 2400L, then be cooled to 0-5 DEG C of growing the grain 1.6 hours, is transferred to three-in-one;
(3) it filters, ethyl acetate washing is passed through 24 DEG C of nitrogen predryings 0.5 hour, later on stirring, by nitrogen liter
Temperature to 38 DEG C it is 3 hours dry, then material is warming up to after 38 DEG C to continue to be passed through nitrogen 3 hours dry, discharging, stirring, crush, point
Dress is to get finished product.
Embodiment 4:
The preparation of cefotiam hydrochloride:
(1) cefotiam hydrochloride crude product 90kg is added in treatment tank, is dissolved with water for injection, adds 150g sodium sulfite-
EDTA, dissolved clarification.It is 0.4 that enriching hydrochloric acid, which is adjusted to PH, adds 350L ethyl acetate.Active carbon decoloring, filtering is added.
(2) filtrate is transferred in crystallization apparatus, quickly stirs, and adds ethyl acetate, formation supersaturation stirring while adding
Liquid is cooled to 14 DEG C, and crystal seed is added, adds ethyl acetate 2800L, then be cooled to 0-5 DEG C of growing the grain 1.5 hours, is transferred to three-in-one;
(3) it filters, ethyl acetate washing is passed through 20 DEG C of nitrogen predryings 1 hour, later on stirring, by nitrogen temperature
It is 1.5 hours dry to 40 DEG C, then material is warming up to after 42 DEG C to continue to be passed through nitrogen 2 hours dry, discharging, stirring, crush, point
Dress is to get finished product.
Comparative example 1:
The preparation of cefotiam hydrochloride: drying means used in its step (3) is to filter, and ethyl acetate washing is passed through 23 DEG C
Nitrogen predrying 0.5 hour, later on stirring, by nitrogen temperature to 30 DEG C it is 1 hour dry, discharging stirring, crushes, packing,
It gets product.Remaining step is same as Example 1.
Comparative example 2:
The preparation of cefotiam hydrochloride: drying means used in its step (3) is to filter, and ethyl acetate washing is passed through 22 DEG C
Nitrogen predrying 1 hour, later on stirring continued to be passed through nitrogen drying 2 hours, then the crystallization of gained cefotiam hydrochloride is turned
Enter single cone drier, 40 DEG C are dried in vacuo 2 hours, and stirring is crushed, dispensed to get finished product.Remaining step is same as Example 2.
Comparative example 3:
The preparation of cefotiam hydrochloride: drying means used in its step (3) is to filter, and ethyl acetate washing is passed through 24 DEG C
Nitrogen predrying 0.5 hour, later on stirring, water flowing steam 5 hours, then the crystallization of gained cefotiam hydrochloride is transferred to single cone
Drier, 40 DEG C are dried in vacuo 3.5 hours, and stirring is crushed, dispensed to get finished product.Remaining step is same as Example 3.
Comparative example 4:
The preparation of cefotiam hydrochloride: antioxidant is not used in its step (1).Remaining step is same as Example 4.
Experimental example 1:
Example 1-4 and comparative example 1-4 prepares resulting solid powder respectively, according to Chinese Pharmacopoeia 2015 editions four
(general rule 0832) carries out determination of moisture, and experimental result is shown in Table 1.
1 determination of moisture result of table
Experimental example 2:
Example 1-4 and comparative example 1-4 prepares resulting solid powder respectively, according to Chinese Pharmacopoeia 2015 editions four
(general rule 0861) carries out residual solvent measurement, is shown in Table 2.
2 ethyl acetate determined result of residue of table
Sample number into spectrum | Ethyl acetate residual | Sample number into spectrum | Ethyl acetate residual |
Embodiment 1 | 0.0017% | Comparative example 1 | 0.0067% |
Embodiment 2 | 0.0012% | Comparative example 2 | 0.0045% |
Embodiment 3 | 0.0014% | Comparative example 3 | 0.0083% |
Embodiment 4 | 0.0010% | Comparative example 4 | 0.0015% |
Experimental example 3:
Example 1-4 and comparative example 1-4 prepares resulting solid powder respectively, according to Chinese Pharmacopoeia 2015 editions four
(general rule 9001) carries out stability test, measures sample size.Experimental result is shown in Table 3, table 4.
3 accelerated test assay result of table
Sample number into spectrum | 0 month | 1 month | 3 months | 6 months | 9 months | 12 months |
Embodiment 1 | 99.90% | 99.87% | 99.88% | 99.83% | 99.75% | 99.69% |
Embodiment 2 | 99.93% | 99.90% | 99.88% | 99.85% | 99.78% | 99.75% |
Embodiment 3 | 99.96% | 99.94% | 99.90% | 99.86% | 99.85% | 99.79% |
Embodiment 4 | 99.99% | 99.97% | 99.95% | 99.89% | 99.87% | 99.84% |
Comparative example 1 | 99.70% | 99.65% | 99.58% | 99.51% | 99.39% | 99.22% |
Comparative example 2 | 99.85% | 99.80% | 99.74% | 99.70% | 99.62% | 99.52% |
Comparative example 3 | 99.61% | 99.54% | 99.45% | 99.30% | 98.89% | 98.72% |
Comparative example 4 | 99.50% | 99.37% | 99.02% | 98.80% | 98.54% | 97.72% |
4 long term test assay result of table
The experimental results showed that, cefotiam hydrochloride moisture produced by the invention and ethyl acetate content are low above, can improve
The stability of product, to guarantee that medication is safer.
The above is only a preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, various improvements and modifications may be made without departing from the principle of the present invention, these improvements and modifications are also answered
It is considered as protection scope of the present invention.
Claims (10)
1. a kind of preparation method of cefotiam hydrochloride, it is characterised in that the following steps are included:
(1) cefotiam hydrochloride crude product is added in treatment tank, is dissolved with water for injection, adds antioxidant, dissolved clarification, enriching hydrochloric acid
Be adjusted to strong acidic environment, be added ethyl acetate, then plus active carbon decoloring, filtering;
(2) filtrate is transferred in crystallization apparatus, quickly stirs, and adds ethyl acetate, the supersaturated liquid of formation stirring while adding, drop
Temperature is added crystal seed, adds ethyl acetate, then be cooled to 0-5 DEG C of growing the grain 0.5-3 hours, be transferred to three-in-one to 14 DEG C;
(3) it filters, ethyl acetate washing is passed through 15-25 DEG C of nitrogen predrying 0.1-3 hours, later on stirring, by nitrogen liter
Temperature to 25-55 DEG C it is 0.5-4 hours dry, then to continue to be passed through nitrogen after material is warming up to 30-50 DEG C 0.5-5 hours dry, out
Material stirring, is crushed, is dispensed to get finished product.
2. a kind of preparation method of cefotiam hydrochloride as described in claim 1, which is characterized in that nitrogen is pre- in step (3)
Drying includes: to be passed through 18-24 DEG C of nitrogen 0.5-1 hours, and drying extremely can stirring.
3. a kind of preparation method of cefotiam hydrochloride as described in claim 1, which is characterized in that nitrogen liter in step (3)
Temperature to 30-40 DEG C it is 1-3 hours dry.
4. a kind of preparation method of cefotiam hydrochloride as described in claim 1, which is characterized in that material liter in step (3)
Temperature is 1-4 hours dry to continuing after 35-45 DEG C to be passed through nitrogen.
5. a kind of preparation method of cefotiam hydrochloride as described in claim 1, which is characterized in that dried extremely in step (3)
Water content≤3%.
6. a kind of preparation method of cefotiam hydrochloride as described in claim 1, which is characterized in that resist described in step (1)
Oxidant is sodium sulfite-EDTA, and dosage is the 0.1-0.5% of crude product weight.
7. a kind of preparation method of cefotiam hydrochloride as claimed in claim 6, which is characterized in that step (1) sulfite
Sodium-EDTA dosage is the 0.2% of crude product weight.
8. a kind of preparation method of cefotiam hydrochloride as described in claim 1, which is characterized in that strong described in step (1)
Acidic environment PH is 0.1-1.0.
9. a kind of preparation method of cefotiam hydrochloride as described in claim 1, which is characterized in that second is added in step (1)
Acetoacetic ester weight is 2-5 times of crude product weight.
10. a kind of preparation method of cefotiam hydrochloride as described in claim 1, which is characterized in that in step (2) when growing the grain
Between be 1-2 hours.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201811385439.5A CN109384800B (en) | 2018-11-20 | 2018-11-20 | Preparation method of cefotiam hydrochloride |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201811385439.5A CN109384800B (en) | 2018-11-20 | 2018-11-20 | Preparation method of cefotiam hydrochloride |
Publications (2)
Publication Number | Publication Date |
---|---|
CN109384800A true CN109384800A (en) | 2019-02-26 |
CN109384800B CN109384800B (en) | 2020-05-22 |
Family
ID=65428917
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201811385439.5A Active CN109384800B (en) | 2018-11-20 | 2018-11-20 | Preparation method of cefotiam hydrochloride |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN109384800B (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112625052A (en) * | 2020-12-30 | 2021-04-09 | 苏州盛达药业有限公司 | Cefotiam raw material medicine |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1365362A (en) * | 1999-07-30 | 2002-08-21 | 卫材株式会社 | Process for the preparation of basic anti-biotic-inorganic acid and intermediate oxalates |
CN101948476A (en) * | 2010-09-19 | 2011-01-19 | 苏州致君万庆药业有限公司 | Method for preparing cefotiam hexetil hydrochloride |
CN102898441A (en) * | 2012-10-11 | 2013-01-30 | 南通康鑫药业有限公司 | Method for synthesizing cefotiam |
-
2018
- 2018-11-20 CN CN201811385439.5A patent/CN109384800B/en active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1365362A (en) * | 1999-07-30 | 2002-08-21 | 卫材株式会社 | Process for the preparation of basic anti-biotic-inorganic acid and intermediate oxalates |
CN101948476A (en) * | 2010-09-19 | 2011-01-19 | 苏州致君万庆药业有限公司 | Method for preparing cefotiam hexetil hydrochloride |
CN102898441A (en) * | 2012-10-11 | 2013-01-30 | 南通康鑫药业有限公司 | Method for synthesizing cefotiam |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112625052A (en) * | 2020-12-30 | 2021-04-09 | 苏州盛达药业有限公司 | Cefotiam raw material medicine |
Also Published As
Publication number | Publication date |
---|---|
CN109384800B (en) | 2020-05-22 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN115505051B (en) | Method for refining sodium gluconate | |
CN101381756B (en) | Purification method of super tylosin | |
CN101948476B (en) | Method for preparing cefotiam hexetil hydrochloride | |
CN114040906B (en) | New preparation method of Para Mi Weisan hydrate and water system drying method thereof | |
CN111655739A (en) | Method for removing gas phase impurities in sugammadex sodium and preparing amorphous substance thereof | |
CN109384800A (en) | A kind of preparation method of cefotiam hydrochloride | |
US8895728B2 (en) | Method for preparing cefmenoxime hydrochloride compound | |
CN102924311B (en) | L-ornithine-L-aspartate preparation method | |
CN104341435B (en) | The process for purification of ceftriaxone sodium | |
CN112094281B (en) | Preparation method of cefepime hydrochloride for injection | |
CN103232477A (en) | Cefotiam hydrochloride compound, and preparation method and pharmaceutical composition thereof | |
CN102746324B (en) | Purification method of cefotiam hydrochloride and aseptic powder injection of cefotiam hydrochloride | |
CN106317080A (en) | Ceftazidime compound prepared by adopting coupling crystallization technology and preparation thereof | |
CN103113390B (en) | Sulbactam sodium compound and medical composition of sulbactam sodium compound and mezlocillin sodium | |
CN105198905A (en) | Method for preparing ultrapure marbofloxacin through purification | |
CN101172108A (en) | Prulifloxacin active body injection | |
JP5874871B1 (en) | C-4 "substituted macrolide compounds | |
CN103301468A (en) | High-content luteolin composition | |
CN103127114B (en) | Medicinal composition including piperacillin sodium and sulbactam sodium | |
CN110857308B (en) | Preparation method of ceftazidime for injection | |
CN101157684A (en) | Aspartic acid lomefloxacin hydrate and preparation and uses thereof | |
CN103304580A (en) | Cefepime dihydrochloride compound as well as preparation method and medicine composition thereof | |
CN105153201B (en) | A kind of preparation method of cefozopran hydrochloride | |
CN117088896A (en) | Refining method of ceftiofur hydrochloride | |
CN114249749B (en) | Conversion method of marbofloxacin formate |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |