CN109134509A - A kind of 1/5 water Cefoxitin sodium compound - Google Patents
A kind of 1/5 water Cefoxitin sodium compound Download PDFInfo
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- 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
- C07D501/57—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with a further substituent in position 7, e.g. cephamycines
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- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
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Abstract
The invention discloses a kind of 1/5 water Cefoxitin sodium compound and its preparation methods.Every mole of cefoxitin sodium contains 1/5 mole of water.Cefoxitin sodium crude product is dissolved in water, through active carbon decoloring, filtering；Filtrate is adjusted with acid pH value, and dissolved agent, crystallization is added；After crystal to be dissolved in the mixed solution of water and ethyl alcohol, crystal seed, secondary crystallization is added, filtering, drying obtain Cefoxitin sodium compound.This is easy to operate, and reactant is easy to get, and reaction condition is milder, high income.1/5 water Cefoxitin sodium compound low in hygroscopicity of the invention, good fluidity, impurity content is low, stability is good, has wider application prospect.
Description
Technical field
The invention belongs to chemical engineering medicine crystallization technique field, be related to a kind of 1/5 water Cefoxitin sodium compound and its
Preparation method.
Background technique
Cefoxitin sodium is developed by MSD Corp. of the U.S. earliest, is listed within 1974.Cefoxitin sodium is by inhibiting bacterium
Cell wall synthesis and kill bacterium, and due to the feature in its structure make its to bacteriogenic beta-lactamase have it is very high
Repellence, antibacterial action and the same second generation cephalosporin of antimicrobial spectrum, but it is stronger to the effect of anaerobic bacteria especially bacteroides fragilis,
Beta-lactamase is stablized.It is clinically used in peritonitis and other intraperitoneal, pelvic cavity, gynecological infection, septicemia, the internal membrane of heart
Inflammation, urinary tract infections ((including stranguria syndrome), respiratory tract infection, bone joint infection, skin soft-tissue infection.
It is worth noting that, to always exist hygroscopicity strong, poor fluidity, impurity higher, steady for raw material of cefoxitin sodium medicine
The content of the disadvantages of qualitative poor and therapeutic effect is incomplete, especially raw material of cefoxitin sodium medicine crystallization can be with the time
Passage and gradually generate corresponding variation, certain negative effect is caused to the quality of raw material of cefoxitin sodium drug.Cause
This, optimizes and improves for raw material of cefoxitin sodium medicine crystallization processes, then produces stabilization by relevant preparation skill
Property more preferable, better quality, service performance be more preferable and holding time longer cefoxitin sodium, to guaranteeing raw material of cefoxitin sodium
The overall stability and quality of medicine crystallization processes have very important effect.
In the research and development and Industrialization Projects of the high-end medical product refining crystallization technology of University Of Tianjin Wang Jingkang professor et al.
The Supramolecular Assembling mechanism for the medicine crystal being related to is the research and development based theoretical of high-end medical product.Medicine crystal surpasses
Molecule assembly behavior, it will usually cause its physicochemical property difference, and then be likely to be obtained the compound with new features.
Medicine crystal Supramolecular Assembling mechanism is creatively introduced into the preparation process of cefoxitin sodium by the present invention, is used
In solving the problems, such as cefoxitin sodium production process.By sufficiently investigate temperature in crystal molecule assembling process, solvent,
Influence of the factors such as crystal seed, additive to crystallization, has obtained that a kind of low in hygroscopicity, good fluidity, impurity content is low, property is stable
Cefoxitin sodium compound, the production process is simple, and raw material, reagent price are cheap, be suitable for industrial-scale production.
Summary of the invention
The invention discloses the new solvates of one kind of cefoxitin sodium, are more specifically 1/5 water Cefoxitin sodium
Object is closed, i.e. every mole of Cefoxitin sodium compound contains 1/5 mole of water, molecular formula C16H16N3NaO7S2·1/5H2O, molecular weight are
453.03 structural formula is as follows:
1/5 water Cefoxitin sodium compound of the present invention is prepared, specifically using following crystal Supramolecular Assembling technology
Method is as follows:
Cefoxitin sodium crude product is soluble in water, and active carbon, stirring decoloration, filtering is added in water-bath temperature control；It is adjusted with acid filter
The pH value of liquid；It is slowly added to dissolved agent into above-mentioned solution, filters, with ethanol washing filter cake；Filter cake is dissolved in water and ethyl alcohol
In mixed solution, stirring and dissolving；Crystal seed is added, temperature control stands crystallization, filtering；Filtrate ethanol washing, it is dry, obtain 1/5 water
Cefoxitin sodium compound.
Preferably, the mixing speed in each step reaction is 100~400r/min；It is preferred that 150~250r/min.
Preferably, the bath temperature is 10~60 DEG C；It is preferred that 20~40 DEG C.
Preferably, the filtrate pH value being adjusted with acid is 4~8；It is preferred that 5.5~6.5.
Preferably, the dissolved agent is halogenated hydrocarbons；It is preferred that one of methylene chloride, chloroform or tetrachloromethane.
Preferably, the volume ratio of the water and ethyl alcohol is (4~10): 1；It is preferred that 6:1.
Preferably, the quality that crystal seed is added is the 0.1~1.0% of theoretical cefoxitin sodium quality；It is preferred that 0.5%.
Preferably, after the addition crystal seed, controlled at -5~20 DEG C when crystallization；It is preferred that 0~5 DEG C.
Karl_Fischer method is one of the most single-minded, accurate method in moisture method in various measurement substances, is had been cited as
The standard method of determination of moisture in many substances, especially to organic compound, as a result accurately and reliably.Cephalo west disclosed by the invention
Fourth sodium compound Karl_Fischer method measures water content between 0.73~0.85%.Theoretical water content is 0.79%, can be preliminary
Determine that each Cefoxitin sodium compound of the present invention contains 1/5 mole of water.
1/5 water Cefoxitin sodium compound of the present invention, TG analysis is the results show that Cefoxitin sodium compound
Percentage loss of weight the calculation shows that is about 0.80%.The theoretical single-detector of cefoxitin sodium is 0.79%, Ka Erfeixiushi
It is 0.73~0.85% that method, which measures cefoxitin sodium moisture content, and it is 0.80% that experiment, which measures TG weightlessness, with theoretical water content
Substantially it is consistent.Deviation is probably derived from the solvent loss in drying process.It can be inferred that Cefoxitin sodium compound weightlessness is
Caused by removing water, and every mole of Cefoxitin sodium hydrate contains 1/5 mole of water.As shown in Fig. 1.Data are by heat analysis-mass spectrum
Combined instrument (NETZSCH STA 449C) analysis obtains.Analysis condition are as follows: 2~10mg of sample, alumina crucible, high pure nitrogen are done
Reaction gas and protection gas, flow are respectively 40ml/min and 30ml/min, and heating rate 10K/min, temperature test range is 25
~400 DEG C.Sample decomposition temperature is about 199.8 DEG C.
1/5 water Cefoxitin sodium compound of the present invention, x-ray diffractogram of powder spectrum are 9.21 in 2 θ of the angle of diffraction
± 0.2 °, 11.12 ± 0.2 °, 12.30 ± 0.2 °, 17.11 ± 0.2 °, 19.72 ± 0.2 °, 23.91 ± 0.2 °, 25.69 ±
There is characteristic diffraction peak at 0.2 °, 27.60 ± 0.2 °, the opposite diffracted intensity of the angle of diffraction is respectively 100,25.96,89.27,
60.99,22.09,44.05,22.23,31.62, as shown in Fig. 2.X-ray powder diffraction test condition: Holland
EMPYREAN (sharp shadow) X-ray diffractometer of Panalytical company, CuK α radiation, light pipe voltage 40kV, heater current
300mA, continuous scanning, 0.02 ° of step-length, 8 °/min of scanning speed, scanning range is 2~50 °.
1/5 water Cefoxitin sodium compound of the present invention, infrared spectroscopy are 3444.5 ± 2cm in wave number-1,
1765.2±2cm-1, 1605.6 ± 2cm-1, 1407.9 ± 2cm-1, 1331.0 ± 2cm-1, 1144.5 ± 2cm-1, 1086.3 ±
2cm-1There is characteristic absorption peak at place.As shown in Fig. 3.Examination of infrared spectrum condition are as follows: Agilent Cary 630, pressing potassium bromide troche.
1/5 water Cefoxitin sodium compound of the present invention, dsc analysis without significantly decomposing the results show that put
Thermal spike, as shown in Fig. 4.DSC data is obtained by heat analysis-mass spectrometer (NETZSCH STA 449C) analysis, analyzes item
Part are as follows: 2~10mg of sample, alumina crucible, high pure nitrogen do reaction gas and protection gas, flow be respectively 40ml/min and
30ml/min.10 DEG C/min of heating rate, 25~400 DEG C of temperature range.
Further purpose of the invention provides a kind of pharmaceutical composition containing 1/5 water Cefoxitin sodium compound.It is excellent
Selection of land, described pharmaceutical composition include 1/5 water Cefoxitin sodium compound and the excipient pharmaceutically received.It is highly preferred that medicine
Compositions are selected from pharmaceutically acceptable dosage form.
Detailed description of the invention
Fig. 1 is the TG analysis chart of 1/5 water Cefoxitin sodium compound；
Fig. 2 is the X ray diffracting spectrum of 1/5 water Cefoxitin sodium compound；
Fig. 3 is the FTIR spectrum figure of 1/5 water Cefoxitin sodium compound；
Fig. 4 is the dsc analysis figure of 1/5 water Cefoxitin sodium compound.
Specific embodiment
Below will by specific embodiment, the present invention will be further described, but therefore do not limit the present invention to institute
In the scope of embodiments stated, it should be understood by those skilled in the art that changing to the equivalent replacement that the content of present invention is done, or accordingly
Into still falling within protection scope of the present invention.
The preparation of 1 1/5 water Cefoxitin sodium compound of embodiment
Preparation process: water 100.11g being added into reactor, and water-bath temperature control weighs cefoxitin sodium crude product at 25 DEG C
50.03g is added in reactor, stirring to dissolution；Active carbon 0.09g, stirring decoloration 30min, filtering are added thereto；Use hydrochloric acid
Filtrate pH to 6.1 is adjusted, chloroform is added into above-mentioned solution, filters, washs filter cake with ethyl alcohol 100mL；Filter cake is dissolved in
In the mixed solution 150ml of water and ethyl alcohol (volume ratio 6:1), stirring and dissolving；Crystal seed is added thereto, temperature control to 0~3 DEG C,
Stand crystallization 1.5h, filtering；Filtrate is washed with ethyl alcohol 80mL × 2；Filtrate is set into 40 DEG C of vacuum drying 70min, obtains 1/5 water
Cefoxitin sodium compound 48.72g.
X-ray diffractogram of powder spectrum 2 θ of the angle of diffraction be 9.21 °, 11.12 °, 12.30 °, 17.11 °, 19.72 °,
There is characteristic diffraction peak at 23.91 °, 25.69 °, 27.60 °, the opposite diffracted intensity of the angle of diffraction is respectively 100,25.96,89.27,
60.99,22.09,44.05,22.23,31.62.
FTIR spectrum diagram data is as follows:
| Serial number | Wave number | Area |
| 1 | 3444.485 | 3086.227 |
| 2 | 1765.236 | 286.140 |
| 3 | 1605.564 | 1148.137 |
| 4 | 1407.856 | 874.800 |
| 5 | 1330.950 | 519.216 |
| 6 | 1144.511 | 181.167 |
| 7 | 1086.280 | 202.978 |
It is 99.31% that HPLC method, which detects purity,；It is 0.75% that Karl_Fischer method, which measures moisture, and thermogravimetric analysis weightlessness is
0.80%, it is almost the same with the result (theoretical value 0.79%) of 1/5 water contained in this way；Elemental Analysis theory are as follows: C:
42.42%, H:3.65%, N:9.28%, Na:5.07%, O:25.43%, S:14.15%；Measured value are as follows: C:42.36%, H:
3.63%, N:9.32%, Na:5.10%, O:25.40%, S:14.20%.
The preparation of 2 1/5 water Cefoxitin sodium compound of embodiment
Preparation process: water 100.03g being added into reactor, and water-bath temperature control weighs cefoxitin sodium crude product at 30 DEG C
50.02g is added in reactor, stirring to dissolution；Active carbon 0.08g, stirring decoloration 30min, filtering are added thereto；Use hydrochloric acid
Filtrate pH to 5.6 is adjusted, methylene chloride is added into above-mentioned solution, filters, washs filter cake with ethyl alcohol 100mL；Filter cake is dissolved in
In the mixed solution 150ml of water and ethyl alcohol (volume ratio 7:1), stirring and dissolving；Crystal seed is added thereto, temperature control to 5~8 DEG C,
Stand crystallization 1.5h, filtering；Filtrate is washed with ethyl alcohol 80mL × 2；Filtrate is set into 40 DEG C of vacuum drying 70min, obtains 1/5 water
Cefoxitin sodium compound 48.48g.
X-ray diffractogram of powder spectrum 2 θ of the angle of diffraction be 9.20 °, 11.15 °, 12.23 °, 17.14 °, 19.70 °,
There is characteristic diffraction peak at 23.93 °, 25.73 °, 27.62 °, the opposite diffracted intensity of the angle of diffraction is respectively 100,26.63,85.05,
61.26,22.43,43.46,21.17,31.78.
FTIR spectrum diagram data is as follows:
| Serial number | Wave number | Area |
| 1 | 3444.153 | 3086.419 |
| 2 | 1765.189 | 286.072 |
| 3 | 1605.442 | 1148.531 |
| 4 | 1407.576 | 874.649 |
| 5 | 1331.011 | 519.022 |
| 6 | 1144.078 | 181.089 |
| 7 | 1086.142 | 202.882 |
It is 99.28% that HPLC method, which detects purity,；It is 0.85% that Karl_Fischer method, which measures moisture, and thermogravimetric analysis weightlessness is
0.82%, it is almost the same with the result (theoretical value 0.79%) of 1/5 water contained in this way；Elemental Analysis theory are as follows: C:
42.42%, H:3.65%, N:9.28%, Na:5.07%, O:25.43%, S:14.15%；Measured value are as follows: C:42.39%, H:
3.60%, N:9.33%, Na:5.05%, O:25.47%, S:14.16%.
The preparation of 3 1/5 water Cefoxitin sodium compound of embodiment
Preparation process: water 99.95g being added into reactor, and water-bath temperature control weighs cefoxitin sodium crude product at 37 DEG C
50.01g is added in reactor, stirring to dissolution；Active carbon 0.09g, stirring decoloration 30min, filtering are added thereto；Use hydrochloric acid
Filtrate pH to 6.4 is adjusted, chloroform is added into above-mentioned solution, filters, washs filter cake with ethyl alcohol 100mL；Filter cake is dissolved in
In the mixed solution 150ml of water and ethyl alcohol (volume ratio 5:1), stirring and dissolving；Crystal seed is added thereto, temperature control to 8~10 DEG C,
Stand crystallization 2.0h, filtering；Filtrate is washed with ethyl alcohol 80mL × 2；Filtrate is set into 40 DEG C of vacuum drying 70min, obtains 1/5 water
Cefoxitin sodium compound 48.46g.
X-ray diffractogram of powder spectrum 2 θ of the angle of diffraction be 9.26 °, 11.10 °, 12.33 °, 17.10 °, 19.75 °,
There is characteristic diffraction peak at 23.94 °, 25.65 °, 27.67 °, the opposite diffracted intensity of the angle of diffraction is respectively 100,24.48,89.95,
60.47,22.12,44.88,23.25,32.27.
FTIR spectrum diagram data is as follows:
| Serial number | Wave number | Area |
| 1 | 3443.994 | 3086.383 |
| 2 | 1765.420 | 286.255 |
| 3 | 1605.815 | 1148.073 |
| 4 | 1407.945 | 874.912 |
| 5 | 1331.157 | 518.975 |
| 6 | 1144.319 | 181.401 |
| 7 | 1086.375 | 203.101 |
It is 99.36% that HPLC method, which detects purity,；It is 0.73% that Karl_Fischer method, which measures moisture, and thermogravimetric analysis weightlessness is
0.76%, it is almost the same with the result (theoretical value 0.79%) of 1/5 water contained in this way；Elemental Analysis theory are as follows: C:
42.42%, H:3.65%, N:9.28%, Na:5.07%, O:25.43%, S:14.15%；Measured value are as follows: C:42.46%, H:
3.62%, N:9.25%, Na:5.04%, O:25.49%, S:14.14%.
Comparative example 1 prepares 0.5 hydrate of cefoxitin sodium according to CN104402908A embodiment 1
At room temperature, cefoxitin acid 100g plus methanol 900ml, water 50ml are added in 5000ml flask, is stirred to dissolve,
Add active carbon 1g, stir 30 minutes, filter, 8 DEG C or so stirred in filtrate under the ethyl acetate of sodium iso-octoate 41.2g is added dropwise
100ml and acetone 350ml solution continue to stir 1h after adding, acetone about 2000ml, ethyl alcohol are then slowly added dropwise wherein
300ml, ethyl acetate 20ml, then 6~-5 DEG C of placements are placed 16-24 hours, and solid is precipitated sufficiently, are filtered, a small amount of chloroform
With ethyl alcohol rinse solids 3 times, filter, obtained solid suitable quantity of water dissolution, isopropanol 200ml, ethyl alcohol 300ml, acetone are about
2000ml is that solvent is recrystallized, and 4 DEG C or so are placed 2 hours or so, is placed 2 hours or so then at 0 DEG C or so, then in -6
DEG C or so place 18-24 hour, make to crystallize abundant precipitation, filter, with a small amount of chloroform and acetone rinse solids 3 times, suction filtration, then
Obtained solid is made thinner and is dried in vacuo 3 hours in 26 DEG C or so, then 40 DEG C or so vacuum drying 2h or so, in the relatively wet of environment
In the case that degree control is between about 30-45%, then 40 DEG C or so forced air drying 1h or so, obtain off-white powder 65.2g.
It is 98.75% that HPLC method, which detects purity,；It is 1.90% that Karl_Fischer method, which measures moisture, and thermogravimetric analysis weightlessness is
1.95%, it is almost the same with the result (theoretical value 1.96%) of 1/2 water contained in this way；Elemental Analysis theory are as follows: C:
41.92%, H:3.74%, N:9.17%, Na:5.01%, O:26.17%, S:13.99%；Measured value are as follows: C:41.87%, H:
3.72%, N:9.22%, Na:5.06%, O:26.10%, S:14.03%.
Test example 1 draws moist investigation
Cefoxitin prepared by 1/5 water Cefoxitin sodium compound and comparative example 1 of the present inventor to Examples 1 to 3
0.5 hydrate of sodium draws moist studied.Investigation condition is relative humidity 75% (RH) and relative humidity 92.5% (RH), temperature
Degree is 40 DEG C, and inspection target is the water content in cefoxitin sodium.
Test results in the following table:
As a result: 1/5 water Cefoxitin sodium compound prepared by the present invention draws the moist head significantly lower than prior art preparation
Western 0.5 hydrate of fourth sodium of spore.Illustrate that 1/5 water Cefoxitin sodium compound of the present invention has good stability, is suitble to drug system
The manufacture and long term storage of agent.
2 mobility of test example is investigated
Cefoxitin prepared by 1/5 water Cefoxitin sodium compound and comparative example 1 of the present inventor to Examples 1 to 3
The mobility of 0.5 hydrate of sodium is studied.Angle of repose detection method is to be placed in particle in fixed funnel, makes its freedom
It drops down on horizontal plane, forms the disc accumulation body that a bottom radius is r, the height for measuring accumulation body is H, according to formula tan θ
=H/r is calculated.
Test results in the following table:
As a result: the mobility of 1/5 water Cefoxitin sodium compound prepared by the present invention is significantly better than the cephalo of the prior art
Western 0.5 hydrate of fourth sodium can satisfy the needs of a variety of preparation methods in the preparation process of preparation.
3 purity detecting of test example
Cefoxitin prepared by 1/5 water Cefoxitin sodium compound and comparative example 1 of the present inventor to Examples 1 to 3
The purity of 0.5 hydrate of sodium and the detection of related substance.
Test results in the following table:
As a result: 1/5 water Cefoxitin sodium compound purity prepared by the present invention is higher than cefoxitin sodium prepared by comparative example 1
0.5 hydrate, related substance are lower than 0.5 hydrate of cefoxitin sodium prepared by comparative example 1, and product of the present invention quality is preferable.
4 dissolubility of test example is investigated
Cefoxitin prepared by 1/5 water Cefoxitin sodium compound and comparative example 1 of the present inventor Examples 1 to 3
0.5 hydrate of sodium is dissolved in aqueous solution respectively, shakes 20min, and it is made to calculate Examples 1 to 3, comparative example 1 by detection level
The solubility of standby compound in water.
Solubility testing result
| Embodiment | Solubility |
| Embodiment 1 | 0.85g/ml |
| Embodiment 2 | 0.81g/ml |
| Embodiment 3 | 0.84g/ml |
| Comparative example 1 | 0.52g/ml |
Conclusion: the dissolubility of 1/5 water Cefoxitin sodium compound prepared by the embodiment of the present invention 1~3 is significantly better than comparison
0.5 hydrate of cefoxitin sodium of example 1.
5 study on the stability of test example
Cefoxitin prepared by 1/5 water Cefoxitin sodium compound and comparative example 1 of the present inventor to Examples 1 to 3
0.5 hydrate of sodium has carried out accelerated stability investigation.Investigation condition is 40 DEG C ± 2 DEG C of temperature, is placed 6 months, respectively at 0,1,
2,3,6 the end of month sampled.Inspection target is character, the clarity of solution and color, moisture, particulate matter, content and related object
Matter.
Investigating result see the table below:
As a result: from the above results, by 6 months accelerated tests, sample prepared by the embodiment of the present invention 1~3 was every
Testing index is substantially better than the product of the preparation of comparative example 1, has absolutely proved that 1/5 Cefoxitin sodium compound prepared by the present invention is steady
Qualitative more preferable, quality is better than similar product, while the moisture of Examples 1 to 3, comparative example 1 infers it substantially without significant change
The water contained is the crystallization water, and non-adsorbed water.
1/5 water Cefoxitin sodium compound of the invention is examined through indices and accelerated stability test investigation shows surely
Qualitative good, far superior to 0.5 hydrate of cefoxitin sodium of the prior art, the present invention have unexpected technical effect, matter
Amount is reliable.
The verifying of 6 crystallization water of test example is investigated
It is the crystallization water to sufficiently verify 1/5 water in Cefoxitin sodium compound of the present invention, the present inventor passes through thermogravimetric
Three kinds of analytic approach, 60 DEG C of thermal stability 10 days, vacuum freezedrying weight-loss method methods, investigate the moisture of each embodiment and comparative example
As a result, specific as follows:
1, thermogravimetry
Thermogravimetric analysis is the weightlessness before sample decomposes at high operating temperatures, is the important side for verifying the crystallization water or adsorbing water
Method, the present inventor have carried out thermogravimetric analysis to the Cefoxitin sodium compound of each embodiment and comparative example preparation respectively, have as a result converged
It is total as follows:
| Embodiment | Thermogravimetry weightlessness (%) |
| Embodiment 1 | 0.80 |
| Embodiment 2 | 0.82 |
| Embodiment 3 | 0.76 |
| Comparative example 1 | 1.95 |
As a result, the 1/5 water Cefoxitin sodium compound weightlessness and the result of 1/5 water contained of Examples 1 to 3 preparation
(theoretical value 0.79%) is almost the same；Cefoxitin sodium weightlessness prepared by comparative example 1 and the result of 0.5 water contained are (theoretical
Value 1.96%) it is almost the same.Cefoxitin sodium compound institute prepared by the deduction embodiment of the present invention 1~3 and comparative example 1 is aqueous to be
The crystallization water.
2,60 DEG C thermal stability 10 days
Cefoxitin sodium point prepared by 1/5 water Cefoxitin sodium compound of preparation of the embodiment of the present invention and comparative example 1
It is not placed in 60 DEG C of baking ovens 10 days, detected moisture with Karl_Fischer method respectively at 0,10 day, as a result as follows:
| Embodiment | 0 day (%) | 10 days (%) |
| Embodiment 1 | 0.75 | 0.73 |
| Embodiment 2 | 0.85 | 0.84 |
| Embodiment 3 | 0.73 | 0.72 |
| Comparative example 1 | 1.90 | 1.85 |
As a result, 60 DEG C of high temperature are placed 10 days, the 1/5 water Cefoxitin sodium compound and comparative example 1 of Examples 1 to 3 preparation
The 0.5 hydrate moisture of cefoxitin sodium of preparation infers that the embodiment of the present invention 1~3 and comparative example 1 are made substantially without significant change
Aqueous standby Cefoxitin sodium compound institute is the crystallization water.
3, vacuum freezedrying 10 hours
Cefoxitin sodium point prepared by 1/5 water Cefoxitin sodium compound of preparation of the embodiment of the present invention and comparative example 1
It is not placed in -45 DEG C of freeze driers and vacuumizes 10 hours, detected moisture with Karl_Fischer method respectively at 0,10 hour, as a result such as
Under:
| Embodiment | 0 hour (%) | 10 hours (%) |
| Embodiment 1 | 0.75 | 0.74 |
| Embodiment 2 | 0.85 | 0.82 |
| Embodiment 3 | 0.73 | 0.70 |
| Comparative example 1 | 1.90 | 1.81 |
As a result, -45 DEG C of vacuum freezedryings of low temperature 10 hours, 1/5 water Cefoxitin sodium of Examples 1 to 3 preparation is closed
0.5 hydrate moisture of cefoxitin sodium prepared by object and comparative example 1 without significant change, infers the embodiment of the present invention 1~3 substantially
The Cefoxitin sodium compound institute prepared with comparative example 1 is aqueous for the crystallization water.
Claims (4)
1. a kind of 1/5 water Cefoxitin sodium compound, which is characterized in that every mole of cefoxitin sodium contains 1/5 mole of water, molecular formula
For C16H16N3NaO7S2·1/5H2O, molecular weight 453.03, structural formula is as follows:
2. a kind of pharmaceutical composition, it is characterised in that include 1/5 water Cefoxitin sodium compound described in claim 1.
3. a kind of pharmaceutical composition, it is characterised in that include 1/5 water Cefoxitin sodium compound described in claim 1 and pharmacy
The excipient of upper receiving.
4. pharmaceutical composition according to claim 3, it is characterised in that described pharmaceutical composition is selected from pharmaceutically acceptable
Dosage form.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102942577A (en) * | 2012-12-04 | 2013-02-27 | 罗诚 | Cefoxitin sodium compound-containing pharmaceutical composition |
| CN103601739A (en) * | 2013-11-26 | 2014-02-26 | 悦康药业集团有限公司 | Cefoxitin sodium compound and preparation method thereof |
| CN104622695A (en) * | 2015-03-10 | 2015-05-20 | 华北制药河北华民药业有限责任公司 | Cefoxitin sodium powder preparation for injection |
| CN105287600A (en) * | 2015-12-03 | 2016-02-03 | 南京多宝生物科技有限公司 | Gram-negative bacterium-resistant cefoxitin sodium freeze-dried powder for injection |
| CN109096310A (en) * | 2017-06-20 | 2018-12-28 | 梁怡 | A kind of 1/4 water Cefoxitin sodium compound |
-
2017
- 2017-06-16 CN CN201710455027.3A patent/CN109134509A/en not_active Withdrawn
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102942577A (en) * | 2012-12-04 | 2013-02-27 | 罗诚 | Cefoxitin sodium compound-containing pharmaceutical composition |
| CN103601739A (en) * | 2013-11-26 | 2014-02-26 | 悦康药业集团有限公司 | Cefoxitin sodium compound and preparation method thereof |
| CN104622695A (en) * | 2015-03-10 | 2015-05-20 | 华北制药河北华民药业有限责任公司 | Cefoxitin sodium powder preparation for injection |
| CN105287600A (en) * | 2015-12-03 | 2016-02-03 | 南京多宝生物科技有限公司 | Gram-negative bacterium-resistant cefoxitin sodium freeze-dried powder for injection |
| CN109096310A (en) * | 2017-06-20 | 2018-12-28 | 梁怡 | A kind of 1/4 water Cefoxitin sodium compound |
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