CN109096310A - A kind of 1/4 water Cefoxitin sodium compound - Google Patents
A kind of 1/4 water Cefoxitin sodium compound Download PDFInfo
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- CN109096310A CN109096310A CN201710467988.6A CN201710467988A CN109096310A CN 109096310 A CN109096310 A CN 109096310A CN 201710467988 A CN201710467988 A CN 201710467988A CN 109096310 A CN109096310 A CN 109096310A
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- water
- cefoxitin sodium
- sodium compound
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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
-
- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Abstract
The invention discloses a kind of 1/4 water Cefoxitin sodium compound and its preparation methods.Every mole of cefoxitin sodium contains 1/4 mole of water.Preparation method is simple, and reactant is easy to get, and reaction condition is milder, high income.1/4 water Cefoxitin sodium compound size distribution of the invention is good, good fluidity, impurity content are low, Thermodynamically stable, has wider application prospect.
Description
Technical field
The invention belongs to chemical engineering medicine crystallization technique field, be related to a kind of 1/4 water Cefoxitin sodium compound and its
Preparation method.
Background technique
Cefoxitin sodium (Cefoxitin Sodium) is developed by Merck company of the U.S., CAS 33564-30-6, molecule
Formula C16H16N3NaO7S2, molecular weight 449.43, chemical name is (6R, 7S) -3- (carbamoyloxymethyl) -7- methoxyl group -
8- oxo -7- [2- (2- thienyl) acetylamino] -5- thia -1- azabicyclo [4.2.0] oct-2-ene -2- carboxylic acid sodium salt,
Structural formula is as follows:
Cefoxitin sodium is the cephamycin C that is generated by streptomycete through semi-synthetic a kind of new antibiotic obtained,
By inhibiting the synthesis of bacteria cell wall to kill bacterium.Cefoxitin sodium is as second generation cephalosporin class antibiotic, with
Generation cephalosporin compares, and antimicrobial spectrum is wider.The medicine is highly sensitive to the negative aerobic and anaerobism pathogenic bacteria of Gram-positive, faces
It is mainly used for treating pulmonary infection urinary system infection contamination and the diseases such as complication and upper lower respiratory tract infection on bed, has good
Application prospect.
There are size distribution unevenness, poor fluidity, impurity compared with same kind of products at abroad for domestic cefoxitin sodium at present
Higher, the problems such as stability is poor.And caused by these problems mainly fall behind as preparation method.These problems there are one
Aspect is unstable between causing product quality poor and criticizing, and in addition also leads to raising and the raw material of production cost to a certain extent
Waste.
To solve the above problems, preparing a kind of good size distribution, good fluidity, the cephalo that impurity content is low, property is stable
Western fourth sodium compound is particularly important.
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 can 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 good size distribution, good fluidity, impurity content is low, property is steady
Fixed Cefoxitin sodium compound, the production process is simple, and raw material, reagent price are cheap, is suitable for industrial-scale production.
Summary of the invention
The invention discloses the new solvates of one kind of cefoxitin sodium, are more specifically 1/4 water Cefoxitin sodium
Object is closed, i.e. every mole of Cefoxitin sodium compound contains 1/4 mole of water, molecular formula C16H16N3NaO7S2·1/4H2O, molecular weight are
453.94 structural formula is as follows:
1/4 water Cefoxitin sodium compound of the present invention is prepared, specifically using following crystal Supramolecular Assembling technology
Method is as follows:
(1) cefoxitin acid is soluble in water, triethylamine is added dropwise in stirring and dissolving, temperature control thereto, stirs evenly；Activity is added
Carbon decoloring, filtering, with a small amount of washing filter cake；The solution that salt forming agent and ethyl alcohol are formed is added dropwise into filtrate, finishes, is slowly added to third
Off-white powder is precipitated in ketone；Filtering, vacuum drying, obtains cefoxitin sodium crude product；
(2) cefoxitin sodium crude product is soluble in water, it is slowly added to acetone thereto, temperature control stands crystallization；Filtering, mistake
Screening acetone washing, vacuum drying, obtains 1/4 water Cefoxitin sodium compound.
Preferably, it is 100~400r/min that mixing speed is reacted in each step；It is preferred that mixing speed be 150~
200r/min。
Preferably, temperature when triethylamine being added dropwise in the step (1) is -5~15 DEG C；It is preferred that 0~5 DEG C.
Preferably, salt forming agent is sodium hydroxide, sodium bicarbonate, sodium carbonate, one in sodium iso-octoate in the step (1)
Kind；It is preferred that sodium iso-octoate.
Preferably, the mass ratio of cefoxitin acid, salt forming agent and ethyl alcohol is 2.57:(0.4~1.8 in the step (1)):
4.5；Preferred mass ratio is 2.57:1.5:4.5.
Preferably, the time that acetone is added in the step (2) controls in 0.5~2h, preferably 1.5h.
Preferably, for crystallization controlled at -5~15 DEG C, the time is 0.5~4h in above-mentioned steps (2)；Preferable temperature is 0
~5 DEG C, the time is 1~2h.
Preferably, drying temperature is 30~50 DEG C in above-mentioned steps；It is preferred that 35~40 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 moisture weight content between 0.90~1.12%.Theoretical water content is 0.99%,
It can primarily determine that each Cefoxitin sodium compound of the present invention contains 1/4 mole of water.
1/4 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 1.09%.The theoretical single-detector of cefoxitin sodium is 0.99%, Ka Erfeixiushi
It is 0.90~1.12% that method, which measures cefoxitin sodium moisture content, and it is 1.09% 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
It removes caused by water.And every mole of Cefoxitin sodium compound contains 1/4 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 200.7 DEG C.
1/4 water Cefoxitin sodium compound of the present invention, x-ray diffractogram of powder spectrum are 9.18 in 2 θ of the angle of diffraction
± 0.2 °, 11.14 ± 0.2 °, 12.30 ± 0.2 °, 17.26 ± 0.2 °, 19.71 ± 0.2 °, 23.90 ± 0.2 °, 25.62 ±
There is characteristic diffraction peak at 0.2 °, 27.32 ± 0.2 °, the opposite diffracted intensity of the angle of diffraction is respectively 100,19.45,79.27,
38.52,22.99,34.12,21.19,25.85, 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 °.
1/4 water Cefoxitin sodium compound of the present invention, FTIR spectrum wave number be 3449.2 ±
2cm-1, 1764.6 ± 2cm-1, 1607.6 ± 2cm-1, 1407.0 ± 2cm-1, 1330.5 ± 2cm-1, 1144.5 ± 2cm-1,
1085.8±2cm-1There is characteristic absorption peak at place, as shown in Fig. 3.Examination of infrared spectrum condition are as follows: Agilent Cary 630, bromination
Potassium tabletting.
1/4 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 1/4 water Cefoxitin sodium compound.It is excellent
Selection of land, described pharmaceutical composition include 1/4 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 that the TG of 1/4 water Cefoxitin sodium compound schemes；
Fig. 2 is the X ray diffracting spectrum of 1/4 water Cefoxitin sodium compound；
Fig. 3 is the FTIR spectrum figure of 1/4 water Cefoxitin sodium compound；
Fig. 4 is that the DSC of 1/4 water Cefoxitin sodium compound schemes.
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 embodiment 1:1/4 water Cefoxitin sodium compound
Preparation process:
(1) cefoxitin acid 25.71g is dissolved in 50mL water, stirring and dissolving, controls temperature at 0~5 DEG C, drips thereto
Add triethylamine 4.0mL, stirs evenly；Active carbon 0.21g decoloration, filtering, with a small amount of washing filter cake is added；Isooctyl acid is added dropwise into filtrate
The solution that sodium 15.21g and ethyl alcohol 45mL is formed, finishes, and stirs, and is slowly added to acetone 25mL, and off-white powder is precipitated；Filtering,
40 DEG C of vacuum drying, obtain cefoxitin sodium crude product 26.36g；
(2) cefoxitin sodium crude product 26.36g is dissolved in 50mL water, is slowly added to acetone 25mL thereto, control temperature
It is 0~3 DEG C, stands crystallization 1.5h；Filtering, filtrate are washed with acetone 40mL × 2, and 40 DEG C of vacuum drying 55min obtain 1/4 water
Cefoxitin sodium compound 25.79g.
X-ray diffractogram of powder spectrum 2 θ of the angle of diffraction be 9.18 °, 11.14 °, 12.30 °, 17.26 °, 19.71 °,
There is characteristic diffraction peak at 23.90 °, 25.62 °, 27.32 °, the opposite diffracted intensity of the angle of diffraction is respectively 100,19.45,79.27,
38.52,22.99,34.12,21.19,25.85.
FTIR spectrum diagram data is as follows:
| Serial number | Wave number | Area |
| 1 | 3449.196 | 979.424 |
| 2 | 1764.602 | 197.550 |
| 3 | 1607.628 | 1204.511 |
| 4 | 1406.966 | 784.926 |
| 5 | 1330.452 | 491.452 |
| 6 | 1144.515 | 149.707 |
| 7 | 1085.813 | 185.483 |
It is 99.37% that HPLC method, which detects purity,；It is 1.05% that Karl_Fischer method, which measures moisture, and thermogravimetric analysis weightlessness is
1.09%, it is almost the same with the result (theoretical value 0.99%) of 1/4 water contained in this way；Elemental Analysis theory are as follows: C:
42.34%, H:3.66%, N:9.26%, Na:5.06%, O:25.55%, S:14.13%；Measured value are as follows: C:42.35%, H:
3.64%, N:9.28%, Na:5.03%, O:25.56%, S:14.14%.
The preparation of embodiment 2:1/4 water Cefoxitin sodium compound
Preparation process:
(1) cefoxitin acid 25.69g is dissolved in 50mL water, stirring and dissolving, controls temperature at -5~0 DEG C, drips thereto
Add triethylamine 4.0mL, stirs evenly；Active carbon 0.24g decoloration, filtering, with a small amount of washing filter cake is added；Hydroxide is added dropwise into filtrate
The solution that sodium 5.54g and ethyl alcohol 17mL is formed, finishes, and stirs, and is slowly added to acetone 25mL, and off-white powder is precipitated；Filtering, 35
DEG C vacuum drying, obtain cefoxitin sodium crude product 26.53g；
(2) cefoxitin sodium crude product 26.53g is dissolved in 50mL water, is slowly added to acetone 25mL thereto, control temperature
It is 5~8 DEG C, stands crystallization 2h；Filtering, filtrate are washed with acetone 40mL × 2, and 40 DEG C of vacuum drying 55min obtain 1/4 head
The western fourth sodium compound 25.68g of spore.
X-ray diffractogram of powder spectrum 2 θ of the angle of diffraction be 9.15 °, 11.16 °, 12.33 °, 17.31 °, 19.74 °,
There is characteristic diffraction peak at 23.95 °, 25.66 °, 27.38 °, the opposite diffracted intensity of the angle of diffraction is respectively 100,22.35,78.41,
35.69,23.48,35.66,22.74,26.11.
FTIR spectrum diagram data is as follows:
| Serial number | Wave number | Area |
| 1 | 3449.272 | 979.258 |
| 2 | 1764.585 | 197.475 |
| 3 | 1607.596 | 1204.309 |
| 4 | 1406.871 | 784.891 |
| 5 | 1330.185 | 491.572 |
| 6 | 1144.309 | 149.622 |
| 7 | 1085.778 | 185.379 |
It is 99.21% that HPLC method, which detects purity,；It is 1.12% that Karl_Fischer method, which measures moisture, and thermogravimetric analysis weightlessness is
1.06%, it is almost the same with the result (theoretical value 0.99%) of 1/4 water contained in this way；Elemental Analysis theory are as follows: C:
42.34%, H:3.66%, N:9.26%, Na:5.06%, O:25.55%, S:14.13%；Measured value are as follows: C:42.36%, H:
3.67%, N:9.25%, Na:5.07%, O:25.53%, S:14.12%.
The preparation of embodiment 3:1/4 water Cefoxitin sodium compound
Preparation process:
(1) cefoxitin acid 25.65g is dissolved in 50mL water, stirring and dissolving, controls temperature at 5~8 DEG C, drips thereto
Add triethylamine 4.0mL, stirs evenly；Active carbon 0.18g decoloration, filtering, with a small amount of washing filter cake is added；Isooctyl acid is added dropwise into filtrate
The solution that sodium 15.24g and ethyl alcohol 45mL is formed, finishes, and stirs, and is slowly added to acetone 25mL, and off-white powder is precipitated；Filtering,
45 DEG C of vacuum drying, obtain cefoxitin sodium crude product 26.57g；
(2) cefoxitin sodium crude product 26.57g is dissolved in 50mL water, is slowly added to acetone 25mL thereto, control temperature
It is -3~0 DEG C, stands crystallization 2h；Filtering, filtrate are washed with acetone 40mL × 2, and 40 DEG C of vacuum drying 55min obtain 1/4 head
The western fourth sodium compound 25.81g of spore.
X-ray diffractogram of powder spectrum 2 θ of the angle of diffraction be 9.15 °, 11.12 °, 12.27 °, 17.21 °, 19.69 °,
There is characteristic diffraction peak at 23.85 °, 25.56 °, 27.30 °, the opposite diffracted intensity of the angle of diffraction is respectively 100,20.34,78.58,
36.71,21.53,33.20,20.75,24.19.
FTIR spectrum diagram data is as follows:
| Serial number | Wave number | Area |
| 1 | 3448.917 | 979.511 |
| 2 | 1764.102 | 197.607 |
| 3 | 1607.635 | 1204.650 |
| 4 | 1406.522 | 784.759 |
| 5 | 1330.577 | 491.397 |
| 6 | 1144.627 | 149.814 |
| 7 | 1085.902 | 185.603 |
It is 99.19% that HPLC method, which detects purity,；It is 0.90% that Karl_Fischer method, which measures moisture, and thermogravimetric analysis weightlessness is
1.00%, it is almost the same with the result (theoretical value 0.99%) of 1/4 water contained in this way；Elemental Analysis theory are as follows: C:
42.34%, H:3.66%, N:9.26%, Na:5.06%, O:25.55%, S:14.13%；Measured value are as follows: C:42.34%, H:
3.68%, N:9.27%, Na:5.04%, O:25.56%, S:14.11%.
Comparative example 1 prepares cefoxitin sodium anhydride according to the method for CN102358744A embodiment 1
Cefoxitin sodium crude product 1kg is taken, it is 7: 2.8 that the volume ratio that volume is 15 times of cefoxitin sodium crude product weight, which is added:
0.2 methanol: ethyl alcohol: water mixed solution is heated to flowing back；After cefoxitin sodium crude product dissolved clarification, cefoxitin sodium crude product is added
0.3 times of weight of active carbon decoloring, filtering；The ethyl propionate that volume is 1.5 times of cefoxitin sodium crude product weight is added in filtrate, stops
It only heats, stirs the lower volume that is added dropwise as the ethyl acetate of 0.8 times of cefoxitin sodium crude product weight, the stirring is 18rmp, described
It is added dropwise and is at the uniform velocity added dropwise within time for adding 10 minutes for control；Drop finishes, stirring cooling, and the stirring cooling is under revolving speed 28rmp stirring
5min is cooled to 61 DEG C, then revolving speed 10rmp stirs lower 10min and is cooled to 23 DEG C, stands 19 hours, filtering, the methanol with 6: 4:
Ethyl acetate solution washs 2 times, 0.25 times every time, 40 DEG C of dry 30min, obtains the cefoxitin sodium crystalline compounds,
Yield 91.9%.
It is 99.03% that HPLC method, which detects purity,；It is 0.29% that Karl_Fischer method, which measures moisture, and thermogravimetric analysis weightlessness is
0.32%, it is almost the same with anhydride result in this way；Elemental Analysis theory are as follows: C:42.76%, H:3.59%, N:9.35%,
Na:5.12%, O:24.92%, S:14.27%；Measured value are as follows: C:42.73%, H:3.57%, N:9.37%, Na:5.15%,
O:24.90%, S:14.29%.
1 size distribution of test example is investigated
Cefoxitin sodium prepared by 1/4 water Cefoxitin sodium compound and comparative example 1 of the present inventor to embodiment 1 without
The size distribution of water object is studied.
Test results in the following table:
As a result: 1/4 water Cefoxitin sodium compound size distribution prepared by the present invention is compared with Cefoxitin prepared by comparative example 1
Sodium anhydride is concentrated, and granule size can be adjusted, and is able to satisfy the needs of different preparation preparations.
2 mobility of test example is investigated
Cefoxitin sodium prepared by 1/4 water Cefoxitin sodium compound and comparative example 1 of the present inventor to embodiment 1 without
The mobility of water object is studied.Angle of repose detection method is to be placed in particle in fixed funnel, its is made freely to drop down onto water
In plane, the disc accumulation body that a bottom radius is r is formed, the height for measuring accumulation body is H, according to formula tan θ=H/r
It calculates.
Test results in the following table:
As a result: cephalo west of the mobility of 1/4 water Cefoxitin sodium compound prepared by the present invention significantly better than comparative example 1
Fourth sodium anhydride can satisfy the needs of a variety of preparation methods in the preparation process of preparation.
3 purity detecting of test example
Cefoxitin sodium prepared by 1/4 water Cefoxitin sodium compound and comparative example 1 of the present inventor to embodiment 1 without
The purity of water object and related substance are detected.
Test results in the following table:
As a result: 1/4 water Cefoxitin sodium compound purity prepared by the present invention is higher than cefoxitin sodium prepared by comparative example 1
Anhydride, related substance are lower than cefoxitin sodium anhydride prepared by comparative example 1, and product of the present invention quality is preferable.
4 dissolubility of test example is investigated
Cefoxitin sodium prepared by 1/4 water Cefoxitin sodium compound and comparative example 1 of the present inventor embodiment 1 without
Water object difference is soluble in water, shakes 20min, calculates cefoxitin sodium prepared by embodiment 1, comparative example 1 by detection level
The solubility of compound in water.
Solubility testing result
| Embodiment | Solubility |
| Embodiment 1 | 0.82g/ml |
| Comparative example 1 | 0.55g/ml |
Conclusion: the dissolubility of 1/4 water Cefoxitin sodium compound prepared by the embodiment of the present invention 1 is significantly better than comparative example 1
Cefoxitin sodium anhydride.
5 study on the stability of test example
Cefoxitin sodium prepared by 1/4 water Cefoxitin sodium compound and comparative example 1 of the present inventor to embodiment 1 without
Water object 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, June
End sampling.Inspection target is character, the clarity of solution and color, moisture, particulate matter, content and related substance.
Investigating result see the table below:
As a result: from the above results, by 6 months accelerated tests, sample items prepared by the embodiment of the present invention 1 were detected
Index is substantially better than the product of the preparation of comparative example 1, has absolutely proved 1/4 Cefoxitin sodium compound stability prepared by the present invention
More preferably, quality is better than similar product, while the moisture of embodiment 1 infers the water that it contains for crystallization substantially without significant change
Water, and non-adsorbed water.
1/4 water Cefoxitin sodium compound of the invention is examined through indices and accelerated stability test investigation shows surely
Qualitative good, far superior to the cefoxitin sodium anhydride of comparative example 1, the present invention have unexpected technical effect, and quality can
It leans on.
The verifying of 6 crystallization water of test example is investigated
It is the crystallization water to sufficiently verify 1/4 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 | 1.09 |
| Embodiment 2 | 1.06 |
| Embodiment 3 | 1.00 |
| Comparative example 1 | 0.32 |
As a result, the 1/4 water Cefoxitin sodium compound weightlessness and the result of 1/4 water contained of Examples 1 to 3 preparation
(theoretical value 0.99%) is almost the same；Comparative example 1 prepare cefoxitin sodium weightlessness with it is little with anhydride theoretical value difference.It pushes away
Aqueous Cefoxitin sodium compound institute prepared by the disconnected embodiment of the present invention 1~3 is the crystallization water, Cefoxitin prepared by comparative example 1
Sodium compound institute is aqueous for absorption water.
2,60 DEG C thermal stability 10 days
Cefoxitin sodium point prepared by 1/4 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 | 1.05 | 1.03 |
| Embodiment 2 | 1.12 | 1.11 |
| Embodiment 3 | 0.90 | 0.89 |
| Comparative example 1 | 0.29 | 0.13 |
As a result, 60 DEG C of high temperature are placed 10 days, 1/4 water Cefoxitin sodium compound moisture of Examples 1 to 3 preparation does not have substantially
There is significant change, cefoxitin sodium moisture prepared by comparative example 1 is substantially reduced, and infers cephalo prepared by the embodiment of the present invention 1~3
Aqueous western fourth sodium compound institute is the crystallization water, and Cefoxitin sodium compound institute prepared by comparative example 1 is aqueous for absorption water.
3, vacuum freezedrying 10 hours
Cefoxitin sodium point prepared by 1/4 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 | 1.05 | 1.03 |
| Embodiment 2 | 1.12 | 1.10 |
| Embodiment 3 | 0.90 | 0.88 |
| Comparative example 1 | 0.29 | 0.11 |
As a result, -45 DEG C of vacuum freezedryings of low temperature 10 hours, 1/4 water Cefoxitin sodium of Examples 1 to 3 preparation is closed
Substantially without significant change, cefoxitin sodium moisture prepared by comparative example 1 is substantially reduced object moisture, infers the embodiment of the present invention 1
The aqueous Cefoxitin sodium compound institute of~3 preparations is the crystallization water, and Cefoxitin sodium compound institute prepared by comparative example 1 is aqueous to be
Adsorb water.
Claims (4)
1. a kind of 1/4 water Cefoxitin sodium compound, which is characterized in that every mole of cefoxitin sodium contains 1/4 mole of water, molecular formula
For C16H16N3NaO7S2·1/4H2O, molecular weight 453.94, structural formula is as follows:
2. a kind of pharmaceutical composition, it is characterised in that include 1/4 water Cefoxitin sodium compound described in claim 1.
3. a kind of pharmaceutical composition, it is characterised in that include 1/4 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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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710467988.6A CN109096310A (en) | 2017-06-20 | 2017-06-20 | A kind of 1/4 water Cefoxitin sodium compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710467988.6A CN109096310A (en) | 2017-06-20 | 2017-06-20 | A kind of 1/4 water Cefoxitin sodium compound |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN109134509A (en) * | 2017-06-16 | 2019-01-04 | 李双喜 | A kind of 1/5 water Cefoxitin sodium compound |
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| CN104402908A (en) * | 2014-10-23 | 2015-03-11 | 胡梨芳 | Cefoxitin sodium compound entity and composition and uses thereof |
| CN104926836A (en) * | 2015-05-28 | 2015-09-23 | 浙江长典医药有限公司 | Cefoxitin sodium compound entity for children and preparation of cefoxitin sodium compound entity for children |
| CN105315300A (en) * | 2014-05-26 | 2016-02-10 | 海口市制药厂有限公司 | Cefoxitin sodium, preparation method and uses thereof |
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| WO2004083217A1 (en) * | 2003-03-20 | 2004-09-30 | Orchid Chemicals & Pharmaceuticals Ltd | An improved process for the preparation of cefoxitin |
| CN101007812A (en) * | 2007-01-26 | 2007-08-01 | 深圳信立泰药业有限公司 | Antibacterial drugs cefoxitin preparation process |
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| CN104402908A (en) * | 2014-10-23 | 2015-03-11 | 胡梨芳 | Cefoxitin sodium compound entity and composition and uses thereof |
| CN104926836A (en) * | 2015-05-28 | 2015-09-23 | 浙江长典医药有限公司 | Cefoxitin sodium compound entity for children and preparation of cefoxitin sodium compound entity for children |
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| CN109134509A (en) * | 2017-06-16 | 2019-01-04 | 李双喜 | A kind of 1/5 water Cefoxitin sodium compound |
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Application publication date: 20181228 |