CN104610283B - A kind of cefepime hydrochloride compound and its pharmaceutical composition - Google Patents
A kind of cefepime hydrochloride compound and its pharmaceutical composition Download PDFInfo
- Publication number
- CN104610283B CN104610283B CN201510047901.0A CN201510047901A CN104610283B CN 104610283 B CN104610283 B CN 104610283B CN 201510047901 A CN201510047901 A CN 201510047901A CN 104610283 B CN104610283 B CN 104610283B
- Authority
- CN
- China
- Prior art keywords
- cefepime hydrochloride
- hydrochloride compound
- cefepime
- preparation
- filtrate
- 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.)
- Active
Links
Landscapes
- Cephalosporin Compounds (AREA)
Abstract
The invention discloses a kind of cefepime hydrochloride compound, which prepares using the following method: (1) it is cefepime Hydrochloride crude product is soluble in water, select the seperation film that molecular cut off is 500~3000 to carry out membrane separation for removing impurities；(2) solution is added into organic solvent after cleaning, and active carbon is added into acquired solution, stirs, filtering decarbonization, collects filtrate；(3) filtrate is subjected to chromatography column separating purification, mobile phase is the mixed solvent of isopropanol and acetonitrile, and fixed phase stuffing is silica gel or aluminium oxide；(4), after isolating and purifying filtrate concentration, it is spray-dried to get.The invention also discloses a kind of pharmaceutical composition containing the cefepime hydrochloride compound, which is injection sterile powder.Cefepime hydrochloride compound and its pharmaceutical composition impurity of the invention is low, and toxic side effect is few, greatly improves the safety of patient medication.
Description
Technical field
The present invention relates to a kind of cefepime hydrochloride compound and its pharmaceutical compositions, belong to field of pharmaceutical chemistry technology.
Background technique
Cefepime is wide spectrum forth generation cephalosporin, is made by inhibiting the biosynthesis of bacteria cell wall to reach sterilization
With.In vitro test shows there is effect to gram-positive bacteria and negative bacterium.The beta-lactam that this product encodes bacterial chromosome
The affinity of enzyme is low, can quite tolerant majority beta-lactamase hydrolysis, and the intracellular of gram-negative bacteria can be rapidly permeated into.?
In somatic cells, target molecule is penicillin binding protein (PBP).Molecular formula: C19H25ClN6O5S2·HCl·H2O, for white
Or off-white powder；It is micro- smelly, it is tasteless.
Cefepime is a kind of thermally labile and water-soluble very big neutral inner salt, Cefepime there are carboxyl anion,
In conjunction with the proton in aqueous solution, the ionization equilibrium of water is promoted to generate more alkali ions and solution is made to be in alkalescent,
However it is easy to happen the reaction such as degradation and open loop under weak basic condition, and content is caused to decline, impurity increases, yield is low, produces
Object purity is low.
In the prior art, the method that the preparation of high-purity hydrochloric acid Cefepime mostly uses recrystallization.Such as hydrochloric acid cephalo pyrrole
The improvement (Meng Hong etc., Chinese antibiotic magazine, in August, 2005) of oxime synthetic method will be disclosed in the literature in method
In cefepime Hydrochloride crystallization process, using acetone and water as solvent, after crystallization obtains cefepime Hydrochloride crude product, then pass through
Boiling processing obtains the cefepime Hydrochloride that purity is 99.8% (HPLC).For another example patent application 201110444957.1
A kind of synthetic method of cefepime Hydrochloride is disclosed, is also that addition acetone is tied in the crystallisation step of the synthetic method
Crystalline substance, the cefepime Hydrochloride purity being prepared using this method are up to 99.7% (HPLC).
Summary of the invention
It is an object of the present invention to provide a kind of cefepime hydrochloride compounds of new method preparation, make cefepime Hydrochloride
Closing object has many advantages, such as that purity is high, impurity is low, toxic side effect is small.
In order to achieve the above-mentioned object of the invention, this invention takes following technical schemes: a kind of cefepime hydrochloride compound,
The structural formula of the cefepime hydrochloride compound are as follows:
The cefepime hydrochloride compound is prepared using the following method: (1), cefepime Hydrochloride crude product is soluble in water, choosing
The seperation film for being 500~3000 with molecular cut off, carries out membrane separation for removing impurities under the conditions of 0.1~0.5MPa operating pressure；
(2), the cefepime Hydrochloride solution of step (1) is added into organic solvent, activity is added into acquired solution
Charcoal, 40~50 DEG C of 20~30min of stirring, filtering decarbonization collect filtrate；
(3), the filtrate of step (2) is subjected to chromatography column separating purification；The condition of the chromatography column separating purification are as follows: flowing
Mutually be volume ratio 1: 2.5~4 isopropanol and acetonitrile mixed solvent, fixed phase stuffing be silica gel or aluminium oxide, flow velocity be 3~
4.5ml/min, 30~40 DEG C of column temperature；
(4), the filtrate after isolating and purifying is condensed into the concentrate of 20~40 Baume degrees at 60 DEG C, it is spray-dried,
To obtain the final product.
Preferably, film used in separation, impurity removal is aromatic polyamide membrane, sulfonated polysulfone membrane or poly- in the step (1)
Sulfone film.
Preferably, the operating pressure of membrane separation for removing impurities is 0.3MPa in the step (1).
Preferably, organic solvent is the mixed solvent of hexamethylene and acetonitrile that volume ratio is 1:2 in the step (2).
Preferably, the additional amount of active carbon is the 2.5~10% of cefepime Hydrochloride crude product in the step (2).
Preferably, the additional amount of active carbon is the 7.5% of cefepime Hydrochloride crude product in the step (2).
Preferably, in the step (3) chromatography column separating purification condition are as follows: mobile phase be volume ratio 1: 3 isopropyl
The mixed solvent of pure and mild acetonitrile, fixed phase stuffing be silica gel or aluminium oxide, flow velocity 3.5ml/min, 35 DEG C of column temperature.
Preferably, concentration of the concentrate at 60 DEG C is 35 Baume degrees in the step (4).
Preferably, the condition being spray-dried in the step (4) are as follows: 100~140 DEG C of spray dryer inlet temperature,
60~100 DEG C of outlet temperature, 1.6~3.0kgf/cm of centrifugal head operating pressure2。
The present invention also provides a kind of pharmaceutical composition containing the cefepime hydrochloride compound, described pharmaceutical compositions
For injection sterile powder；By weight, the injection sterile powder includes 100 parts of the cefepime hydrochloride compound,
55-65 parts of L-arginine.
Compared with prior art, the invention has the following advantages:
Cefepime hydrochloride compound provided by the invention passes through the suction of membrane separation, activated carbon adsorption and chromatographic column
It is attached to isolate and purify, the purity and content of cefepime hydrochloride compound are substantially increased, and then improve its pharmaceutical composition
Product quality reduces toxic side effect, greatly improves the safety of patient medication；And this method simple process and low cost,
High income is suitable for industrialized production.
Specific embodiment
The application is further elaborated below by way of specific embodiment.
In following embodiment, used raw material is commercially available.
Embodiment 1
A kind of cefepime hydrochloride compound, the cefepime hydrochloride compound are prepared using the following method:
(1), 100g cefepime Hydrochloride crude product (purity 83.2%) is dissolved in 1500ml water, selection molecular cut off is
500~3000 seperation film, aromatic polyamides membrane separation for removing impurities under the conditions of 0.3MPa operating pressure；
(2), the cefepime Hydrochloride solution of step (1) is added to the hexamethylene and acetonitrile that are 1:2 to 1000ml volume ratio
In the mixed solvent, the active carbon of 7.5g is added into acquired solution, keeps the temperature 45 DEG C of stirring 30min, filtering decarbonization is collected and filtered
Liquid；
(3), the filtrate of step (2) is subjected to chromatography column separating purification；The condition of the chromatography column separating purification are as follows: flowing
It is mutually the isopropanol of volume ratio 1: 3 and the mixed solvent of acetonitrile, fixed phase stuffing is silica gel, flow velocity 3.5ml/min, column temperature 35
℃；
(4), the filtrate after isolating and purifying is condensed into the concentrate of 35 Baume degrees (60 DEG C), is spray-dried, spray drying
Condition are as follows: 100~140 DEG C of spray dryer inlet temperature, 60~100 DEG C of outlet temperature, centrifugal head operating pressure 1.6~
3.0kgf/cm2To get.
Determine that resulting compound is cefepime hydrochloride compound by infrared spectroscopy and nuclear magnetic resoance spectrum.
IRυKBrmax cm-13440,1775,1515,1248,1175.
1H-NMR, δ 2.15~2.4,3.13,3.58~3.62,3.70,3.79,3.80,4.2,4.57,5.12,5.15,
5.41,6.88,7.21~7.32,7.84.
13C-NMR, δ 20.82,21.34,22.07,23.59,25.30,42.70,48.06,51.88,53.91,55.30,
61.20,64.35,65.13,68.49,96.06,112.80,114.20,126.39,127.10,129.51,130.47,
131.25,134.68,134.93,160.06,165.59,166.23,171.86.
It can determine that a molecule cefepime Hydrochloride contains 2 molecule hydrochloric acid and 1 molecule knot through elemental analysis and differential thermal analysis
Brilliant water.
Structural formula are as follows:
Purity through HPLC detection cefepime hydrochloride compound is 99.9%.
Embodiment 2
A kind of cefepime hydrochloride compound, the cefepime hydrochloride compound are prepared using the following method:
(1), 100g cefepime Hydrochloride crude product (purity 82.4%) is dissolved in 1500ml water, selection molecular cut off is
500~3000 seperation film, sulfonated polysulfone membrane separation for removing impurities under the conditions of 0.1MPa operating pressure；
(2), the cefepime Hydrochloride solution of step (1) is added to the hexamethylene and acetonitrile that are 1:2 to 1000ml volume ratio
In the mixed solvent, the active carbon of 2.5g is added into acquired solution, keeps the temperature 40 DEG C of stirring 20min, filtering decarbonization is collected and filtered
Liquid；
(3), the filtrate of step (2) is subjected to chromatography column separating purification；The condition of the chromatography column separating purification are as follows: flowing
It is mutually the isopropanol of volume ratio 2: 5 and the mixed solvent of acetonitrile, fixed phase stuffing is silica gel, flow velocity 4.5ml/min, column temperature 35
℃；
(4), the filtrate after isolating and purifying is condensed into the concentrate of 20 Baume degrees (60 DEG C), is spray-dried, spray drying
Condition are as follows: 100~140 DEG C of spray dryer inlet temperature, 60~100 DEG C of outlet temperature, centrifugal head operating pressure 1.6~
3.0kgf/cm2To get.
Determine that resulting compound is cefepime hydrochloride compound by infrared spectroscopy and nuclear magnetic resoance spectrum.
IRυKBrmax cm-13440,1775,1515,1248,1175.
1H-NMR, δ 2.15~2.4,3.13,3.58~3.62,3.70,3.79,3.80,4.2,4.57,5.12,5.15,
5.41,6.88,7.21~7.32,7.84.
13C-NMR, δ 20.82,21.34,22.07,23.59,25.30,42.70,48.06,51.88,53.91,55.30,
61.20,64.35,65.13,68.49,96.06,112.80,114.20,126.39,127.10,129.51,130.47,
131.25,134.68,134.93,160.06,165.59,166.23,171.86.
It can determine that a molecule cefepime Hydrochloride contains 2 molecule hydrochloric acid and 1 molecule knot through elemental analysis and differential thermal analysis
Brilliant water.
Structural formula are as follows:
Purity through HPLC detection cefepime hydrochloride compound is 99.8%.
Embodiment 3
A kind of cefepime hydrochloride compound, the cefepime hydrochloride compound are prepared using the following method:
(1), 100g cefepime Hydrochloride crude product (purity 81.7%) is dissolved in 1500ml water, selection molecular cut off is
500~3000 seperation film, polysulfones membrane separation for removing impurities under the conditions of 0.5MPa operating pressure；
(2), the cefepime Hydrochloride solution of step (1) is added to the hexamethylene and acetonitrile that are 1:2 to 1000ml volume ratio
In the mixed solvent, the active carbon of 10g is added into acquired solution, keeps the temperature 50 DEG C of stirring 25min, filtering decarbonization, collection filtrate；
(3), the filtrate of step (2) is subjected to chromatography column separating purification；The condition of the chromatography column separating purification are as follows: flowing
It is mutually the isopropanol of volume ratio 1: 4 and the mixed solvent of acetonitrile, fixed phase stuffing is aluminium oxide, flow velocity 3ml/min, column temperature 40
℃；
(4), the filtrate after isolating and purifying is condensed into the concentrate of 40 Baume degrees (60 DEG C), is spray-dried, spray drying
Condition are as follows: 100~140 DEG C of spray dryer inlet temperature, 60~100 DEG C of outlet temperature, centrifugal head operating pressure 1.6~
3.0kgf/cm2To get.
Determine that resulting compound is cefepime hydrochloride compound by infrared spectroscopy and nuclear magnetic resoance spectrum.
IRυKBrmax cm-13440,1775,1515,1248,1175.
1H-NMR, δ 2.15~2.4,3.13,3.58~3.62,3.70,3.79,3.80,4.2,4.57,5.12,5.15,
5.41,6.88,7.21~7.32,7.84.
13C-NMR, δ 20.82,21.34,22.07,23.59,25.30,42.70,48.06,51.88,53.91,55.30,
61.20,64.35,65.13,68.49,96.06,112.80,114.20,126.39,127.10,129.51,130.47,
131.25,134.68,134.93,160.06,165.59,166.23,171.86.
It can determine that a molecule cefepime Hydrochloride contains 2 molecule hydrochloric acid and 1 molecule knot through elemental analysis and differential thermal analysis
Brilliant water.
Structural formula are as follows:
Purity 99.5% through HPLC detection cefepime hydrochloride compound.
Embodiment 4
The preparation of cefepime dihydrochloride for injection aseptic powdery:
Aseptically, the cefepime hydrochloride compound 100g of the preparation of embodiment 1 is weighed, L-arginine 55g is placed in
It uniformly mixes in solid powder mixer, is sub-packed in cillin bottle after the assay was approved, jump a queue, Zha Gai, packaging, inspection.
Embodiment 5
The preparation of cefepime dihydrochloride for injection aseptic powdery:
Aseptically, the cefepime hydrochloride compound 100g of the preparation of embodiment 1 is weighed, L-arginine 60g is placed in
It uniformly mixes in solid powder mixer, is sub-packed in cillin bottle after the assay was approved, jump a queue, Zha Gai, packaging, inspection.
Experimental example 1
Compared with product of the present invention substance data related with the accelerated test of reference examples, 1 the results are shown in Table.
Table 1
| 0 month | 1 month | 2 months | 3 months | 6 months | |
| Embodiment 4 | 0.37% | 0.37% | 0.39% | 0.39% | 0.40% |
| Embodiment 5 | 0.39% | 0.36% | 0.38% | 0.38% | 0.40% |
| Commercial product | 0.61% | 0.64% | 0.65% | 0.64% | 0.67% |
Compared with product of the present invention substance data related with the long term test of reference examples, it the results are shown in Table 2.
Table 2
| 0 month | 3 months | 6 months | 9 months | 12 months | 15 months | |
| Embodiment 4 | 0.37% | 0.38% | 0.38% | 0.38% | 0.40% | 0.41% |
| Embodiment 5 | 0.39% | 0.38% | 0.40% | 0.42% | 0.41% | 0.42% |
| Commercial product | 0.61% | 0.61% | 0.63% | 0.65% | 0.67% | 0.68% |
The above results show product of the present invention cefepime dihydrochloride for injection aseptic powdery compared to commercial product, it is related
Content of material is low, and stability is good.
The embodiments described above only express several embodiments of the present invention, and the description thereof is more specific and detailed, but simultaneously
Limitations on the scope of the patent of the present invention therefore cannot be interpreted as.It should be pointed out that for those of ordinary skill in the art
For, without departing from the inventive concept of the premise, various modifications and improvements can be made, these belong to guarantor of the invention
Protect range.Therefore, the scope of protection of the patent of the invention shall be subject to the appended claims.
Claims (7)
1. a kind of preparation method of cefepime hydrochloride compound, which is characterized in that it is described the preparation method comprises the following steps: (1), by hydrochloric acid
Cefepime crude product is soluble in water, and selecting molecular cut off is 500~3000 seperation film, in 0.1~0.5MPa operating pressure
Under the conditions of carry out membrane separation for removing impurities；
(2), the cefepime Hydrochloride solution of step (1) is added into organic solvent, is added active carbon into acquired solution, 40
~50 DEG C of 20~30min of stirring, filtering decarbonization collect filtrate；
(3), the filtrate of step (2) is subjected to chromatography column separating purification；The condition of the chromatography column separating purification are as follows:
Mobile phase be volume ratio 1: 2.5~4 isopropanol and acetonitrile mixed solvent, fixed phase stuffing be silica gel or aluminium oxide,
Flow velocity be 3~4.5ml/min, 30~40 DEG C of column temperature；
(4), the filtrate after isolating and purifying is condensed into the concentrate of 20~40 Baume degrees at 60 DEG C, it is spray-dried to get；
Organic solvent is the mixed solvent of hexamethylene and acetonitrile that volume ratio is 1:2 in the step (2)；
The condition being spray-dried in the step (4) are as follows: 100~140 DEG C of spray dryer inlet temperature, outlet temperature 60~
100 DEG C, 1.6~3.0kgf/cm of centrifugal head operating pressure2。
2. the preparation method of cefepime hydrochloride compound according to claim 1, which is characterized in that
Film used in separation, impurity removal is aromatic polyamide membrane, sulfonated polysulfone membrane or PS membrane in the step (1).
3. the preparation method of cefepime hydrochloride compound according to claim 1, which is characterized in that
The operating pressure of membrane separation for removing impurities is 0.3MPa in the step (1).
4. the preparation method of cefepime hydrochloride compound according to claim 1, which is characterized in that the step (2)
The additional amount of middle active carbon is the 2.5~10% of cefepime Hydrochloride crude product.
5. cefepime hydrochloride compound according to claim 4, which is characterized in that active carbon in the step (2)
Additional amount is the 7.5% of cefepime Hydrochloride crude product.
6. the preparation method of cefepime hydrochloride compound according to claim 1, which is characterized in that the step (3)
The condition of middle chromatography column separating purification are as follows: mobile phase is the isopropanol of volume ratio 1: 3 and the mixed solvent of acetonitrile, fixed phase stuffing
For silica gel or aluminium oxide, flow velocity 3.5ml/min, 35 DEG C of column temperature.
7. the preparation method of cefepime hydrochloride compound according to claim 1, which is characterized in that
Concentration of the concentrate at 60 DEG C is 35 Baume degrees in the step (4).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510047901.0A CN104610283B (en) | 2015-01-30 | 2015-01-30 | A kind of cefepime hydrochloride compound and its pharmaceutical composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510047901.0A CN104610283B (en) | 2015-01-30 | 2015-01-30 | A kind of cefepime hydrochloride compound and its pharmaceutical composition |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104610283A CN104610283A (en) | 2015-05-13 |
| CN104610283B true CN104610283B (en) | 2019-01-11 |
Family
ID=53144961
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510047901.0A Active CN104610283B (en) | 2015-01-30 | 2015-01-30 | A kind of cefepime hydrochloride compound and its pharmaceutical composition |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104610283B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111560028A (en) * | 2020-04-25 | 2020-08-21 | 广东赛法洛药业有限公司 | New indication of cefepime hydrochloride medicinal preparation for treating otitis media |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006067803A1 (en) * | 2004-12-21 | 2006-06-29 | Lupin Limited | A novel intermediate for the preparation of cefepime |
| CN101239065A (en) * | 2008-03-12 | 2008-08-13 | 齐鲁安替制药有限公司 | Method for preparing cefepime dihydrochloride and L-arginine mixed powder |
| CN101773507A (en) * | 2010-02-05 | 2010-07-14 | 王明 | Cefepime hydrochloride/arginine pharmaceutical composition suspension injection |
| CN102010433A (en) * | 2010-12-02 | 2011-04-13 | 郝志艳 | Cefepime hydrochloride compound and new preparation method thereof |
| CN103113391A (en) * | 2012-12-25 | 2013-05-22 | 厦门市天泉鑫膜科技股份有限公司 | Method and equipment for decoloring and purifying 7-aminocephalosporanic acid based on ultra-filtration membrane technique |
| WO2013114319A1 (en) * | 2012-01-31 | 2013-08-08 | Corden Pharma Latina S.P.A. Con Unico Socio | Process for the direct preparation of cefepime for injectable use |
| CN103665003A (en) * | 2013-11-28 | 2014-03-26 | 山东鑫泉医药有限公司 | Refining method of high-purity cefepime dihydrochloride monohydrate |
-
2015
- 2015-01-30 CN CN201510047901.0A patent/CN104610283B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006067803A1 (en) * | 2004-12-21 | 2006-06-29 | Lupin Limited | A novel intermediate for the preparation of cefepime |
| CN101239065A (en) * | 2008-03-12 | 2008-08-13 | 齐鲁安替制药有限公司 | Method for preparing cefepime dihydrochloride and L-arginine mixed powder |
| CN101773507A (en) * | 2010-02-05 | 2010-07-14 | 王明 | Cefepime hydrochloride/arginine pharmaceutical composition suspension injection |
| CN102010433A (en) * | 2010-12-02 | 2011-04-13 | 郝志艳 | Cefepime hydrochloride compound and new preparation method thereof |
| WO2013114319A1 (en) * | 2012-01-31 | 2013-08-08 | Corden Pharma Latina S.P.A. Con Unico Socio | Process for the direct preparation of cefepime for injectable use |
| CN103113391A (en) * | 2012-12-25 | 2013-05-22 | 厦门市天泉鑫膜科技股份有限公司 | Method and equipment for decoloring and purifying 7-aminocephalosporanic acid based on ultra-filtration membrane technique |
| CN103665003A (en) * | 2013-11-28 | 2014-03-26 | 山东鑫泉医药有限公司 | Refining method of high-purity cefepime dihydrochloride monohydrate |
Non-Patent Citations (1)
| Title |
|---|
| 新的第四代头抱菌素头孢吡肟;周延安;《国外医药抗生素分册》;19950930;第16卷(第5期);第344-348页 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104610283A (en) | 2015-05-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106928323B (en) | Preparation method of high-purity oritavancin key intermediate A82846B | |
| CN102718843B (en) | Preparation method of single teicoplanin components | |
| CN105566445B (en) | Method for separating and purifying reduced glutathione | |
| CN104610283B (en) | A kind of cefepime hydrochloride compound and its pharmaceutical composition | |
| CN104961749B (en) | A kind of infant industry crystallization method of Cefuroxime sodium and preparation thereof | |
| CN106432276A (en) | Cefazolin sodium compound prepared according to novel intelligent crystallization technology and preparation of cefazolin sodium compound | |
| CN111635402B (en) | Separation and purification method of pyrroloquinoline quinone | |
| CN109206486B (en) | Polymyxin B sulfate impurity and preparation method thereof | |
| CN111039999A (en) | Synthesis method of etimicin impurity | |
| CN107629115B (en) | Purification method of telavancin | |
| CN107501296B (en) | From the method for Cefprozil crystalline mother solution recycling Cefprozil | |
| CN105198905A (en) | Method for preparing ultrapure marbofloxacin through purification | |
| CN110117310B (en) | Purification method of daptomycin | |
| CN113045611B (en) | Preparation method of high-purity lincomycin hydrochloride | |
| CN112279895B (en) | Preparation method of chemically synthesized acidic polypeptide | |
| CN102363621B (en) | Cefminox sodium hexahydrate, preparation method thereof and pharmaceutical composition containing hexahydrate | |
| CN113845573A (en) | Preparation method of vancomycin impurity G | |
| CN110668922B (en) | Refining method of musk camphor | |
| CN106565784B (en) | The purification process of Ceftaroline Fosamil disodium salt | |
| CN103127114B (en) | Medicinal composition including piperacillin sodium and sulbactam sodium | |
| US8609368B2 (en) | Process for purifying vancomycin wet body | |
| CN109096273A (en) | The method for separating and preparing of mezlocillin sodium impurity C, D and F | |
| CN104892637B (en) | A kind of infant industry crystallization method of Sodium O-formylcefamole and preparation thereof | |
| CN110903346B (en) | Method for preparing vancomycin hydrochloride impurity impC | |
| CN216321130U (en) | Extraction and concentration device for clavulanic acid fermentation liquor |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CP01 | Change in the name or title of a patent holder | ||
| CP01 | Change in the name or title of a patent holder |
Address after: 100176 No. 6, Hongda Middle Road, Beijing economic and Technological Development Zone, Beijing, Daxing District Patentee after: Yuekang Pharmaceutical Group Co., Ltd. Address before: 100176 No. 6, Hongda Middle Road, Beijing economic and Technological Development Zone, Beijing, Daxing District Patentee before: YOUCARE PHARMACEUTICAL GROUP CO., LTD. |