CN109734728A - A kind of cefathiamidine aqueous acetonitrile agent compound monocrystalline and preparation method thereof - Google Patents
A kind of cefathiamidine aqueous acetonitrile agent compound monocrystalline and preparation method thereof Download PDFInfo
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- CN109734728A CN109734728A CN201910091346.XA CN201910091346A CN109734728A CN 109734728 A CN109734728 A CN 109734728A CN 201910091346 A CN201910091346 A CN 201910091346A CN 109734728 A CN109734728 A CN 109734728A
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- cefathiamidine
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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
- C07D501/24—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
- C07D501/26—Methylene radicals, substituted by oxygen atoms; Lactones thereof with the 2-carboxyl group
- C07D501/28—Methylene radicals, substituted by oxygen atoms; Lactones thereof with the 2-carboxyl group with the 7-amino radical acylated by an aliphatic carboxylic acid, which is substituted by hetero atoms
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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
- C07D501/02—Preparation
- C07D501/12—Separation; Purification
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- 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
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Abstract
The invention discloses a kind of cefathiamidine aqueous acetonitrile agent compound monocrystalline and preparation method thereof, which is colorless and transparent rhabdolith, belongs to rhombic system, space group P212121, cell parameter Unit cell volumeContain 2 molecule cefathiamidines, 4 molecule acetonitriles and 2 molecular waters in each structure cell.Preparation method are as follows: cefathiamidine solid and deionized water are configured to the cefathiamidine solution that mass concentration is 0.10~2.00g/mL；Acetonitrile is slowly added dropwise into cefathiamidine solution, so that acetonitrile uniformly spreads over the surface of the solution；It is to stand 12~48 hours at 0 DEG C~25 DEG C that the cefathiamidine solution that surface is uniformly sprawled to acetonitrile, which is placed on temperature, obtains the monocrystalline.The monocrystalline is a kind of cefathiamidine novel crystal forms, and has preferable stability.
Description
Technical field
The present invention relates to Cefathiamidine monocrystal and its preparation technical field more particularly to a kind of cefathiamidine aqueous acetonitrile agent
Compound monocrystalline and preparation method thereof.
Background technique
Cefathiamidine, chemical name (6R, 7R) -3- [(acetoxyl group) methyl] -7- [α-(N, N- diisopropylamidinateand sulfenyl)
Acetylamino] -8- oxo -5- thia -1- azabicyclo [4.2.0] oct-2-ene -2- formic acid betaine, white or off-white color knot
Crystalline substance powder, the molecular weight of anhydride are 472.57900, density 1.45g/cm.Due to its unique betaine structure, not
With being relatively easy to form solvate in solvent.Cefathiamidine belongs to first generation beta-lactam antibiotic, to gram positive bacteria, leather
Blue negative bacterium, Streptococcus viridans etc. have preferable antibacterial action.
Cefathiamidine has the unique molecular structure of amphoteric ion inner salt, and case of thermal instability is preparing cefathiamidine crystal
Process and its storage during, easily degrade, storage it is unstable；And hydrogen bond, product easily are formed with solvent in a solvent
Amorphous powder easy to form causes product purity bottom when precipitation, and quality does not meet medicinal standard；Therefore, to the development of its crystal form
The always hot spot of this field.
Cefathiamidine crystal form reported at present has: CN103556226A, CN1212324, CN100338072C are disclosed
Three kinds of cefathiamidine crystal forms, CN101074235B disclose a kind of cephalo-sulfide alcohol hydro-compound, CN102180890B,
CN104910186B discloses three kinds of cefathiamidine hydrates, and CN1898723 disclosed is a kind of unformed cefathiamidine.To mesh
It is preceding not there is patent disclosure to report cefathiamidine aqueous acetonitrile agent compound monocrystalline yet.
Summary of the invention
The object of the present invention is to provide a kind of cefathiamidine aqueous acetonitrile agent compound monocrystalline and preparation method thereof.
In a first aspect, the present invention provides a kind of cefathiamidine aqueous acetonitrile agent compound monocrystalline, the monocrystalline is colorless and transparent
Rhabdolith belongs to rhombic system, space group P212121, cell parameter Unit cell volumeContain 2 molecule cefathiamidines, 4 molecule acetonitriles and 2 in each structure cell
Molecular water.
Preferably, the molecular formula of the monocrystalline: C46H72N12O14S4, molecular structural formula are as follows:
Second aspect, the present invention also provides the preparation sides of the cefathiamidine aqueous acetonitrile agent compound monocrystalline in first aspect
Method, this method comprises:
Step 1: cefathiamidine solid and deionized water are configured to the cephalo sulphur that mass concentration is 0.10~2.00g/mL
Amidine solution；
Step 2: being slowly added dropwise acetonitrile in Xiang Suoshu cefathiamidine solution, so that acetonitrile uniformly spreads over the solution
Surface；
Step 3: surface is uniformly sprawled acetonitrile cefathiamidine solution be placed on temperature be 0 DEG C~25 DEG C at stand 12~
48 hours, obtain cefathiamidine aqueous acetonitrile agent compound monocrystalline.
Preferably, the mass concentration of cefathiamidine solution is 0.50~1.50g/mL in step 1.
Preferably, the quality for the acetonitrile being added dropwise in step 2 be the cefathiamidine solution in deionized water quality 10~
30 times.
Preferably, the quality for the acetonitrile being added dropwise in step 2 be the cefathiamidine solution in deionized water quality 15~
25 times.
Preferably, the time of repose in step 3 is 24 hours.
Preferably, the dwell temperature in step 3 is 5 DEG C~15 DEG C.
Preferably, the dwell temperature in step 3 is constant.
Technical solution provided by the invention can include the following benefits:
Cefathiamidine aqueous acetonitrile agent compound monocrystalline provided in an embodiment of the present invention is a kind of cefathiamidine from undocumented
Novel crystal forms, and there is preferable stability.Preparation method provided in an embodiment of the present invention can successfully prepare cefathiamidine second
Nitrile water solvates, obtained cefathiamidine aqueous acetonitrile agent compound monocrystalline are a kind of novel crystal forms of cefathiamidine, production method
It is easy to operate, and the advantage that obtained monocrystalline pattern integrity degree is high, cleanliness is high.
It should be understood that above general description and following detailed description be only it is exemplary and explanatory, not
It can the limitation present invention.
Detailed description of the invention
In order to illustrate more clearly of technical solution of the present invention, letter will be made to attached drawing needed in the embodiment below
Singly introduce, it should be apparent that, for those of ordinary skills, without any creative labor,
It is also possible to obtain other drawings based on these drawings.
Fig. 1 is molecular structure in a kind of structure cell of cefathiamidine aqueous acetonitrile agent compound monocrystalline provided in an embodiment of the present invention
Figure；
Fig. 2 is a kind of optical microscope of cefathiamidine aqueous acetonitrile agent compound monocrystalline provided in an embodiment of the present invention
Piece；
Fig. 3 is a kind of petrographic microscope figure of cefathiamidine aqueous acetonitrile agent compound monocrystalline provided in an embodiment of the present invention
Piece；
Fig. 4 is a kind of XRD spectrum of cefathiamidine aqueous acetonitrile agent compound monocrystalline provided in an embodiment of the present invention；
Fig. 5 is a kind of TG map of cefathiamidine aqueous acetonitrile agent compound monocrystalline provided in an embodiment of the present invention；
Fig. 6 is a kind of DSC map of cefathiamidine aqueous acetonitrile agent compound monocrystalline provided in an embodiment of the present invention
Fig. 7 is a kind of IR map of cefathiamidine aqueous acetonitrile agent compound monocrystalline provided in an embodiment of the present invention.
Specific embodiment
A kind of cefathiamidine aqueous acetonitrile agent compound monocrystalline provided in an embodiment of the present invention, physicochemical properties are as follows:
(1) appearance is colorless and transparent rhabdolith；
(2) molecular formula: C46H72N12O14S4；
(3) molecular structural formula:
Cefathiamidine aqueous acetonitrile agent compound single crystal data in the embodiment of the present invention is in German Brooker company Smart
It is acquired on 1000 CCD single crystal diffractometers, using by graphite monochromatised Cu K alpha ray (λ=0.154184nm).It is minimum inclined
Poor factor R1=0.0499, wR2=0.1371.Crystal belongs to rhombic system, space group P212121, cell parameterUnit cell volumeIn each structure cell
Contain 2 molecule cefathiamidines, 4 molecule acetonitriles and 2 molecular waters.Relative molecular mass is 1145.39, density 1.266g/cm3。
Its cell configuration is as shown in Figure 1.
The embodiment of the invention also provides the preparation methods of above-mentioned cefathiamidine aqueous acetonitrile agent compound monocrystalline.
Step 1: cefathiamidine solid and deionized water are configured to the cephalo sulphur that mass concentration is 0.10~2.00g/mL
Amidine solution.
In the specific implementation process, the preferred mass concentration of the cefathiamidine solution of configuration is 0.50~1.50g/mL.
Step 2: being slowly added dropwise acetonitrile in Xiang Suoshu cefathiamidine solution, so that acetonitrile uniformly spreads over the solution
Surface.
In the specific implementation process, the quality for the acetonitrile being added dropwise in step 2 is in the cefathiamidine solution in step 1
10~30 times of ion water quality.In a kind of possible embodiment, the preferred mass of the acetonitrile of dropwise addition is in step 1
15~25 times of deionized water quality in cefathiamidine solution.
Step 3: the cefathiamidine solution that surface is uniformly sprawled to acetonitrile, which is placed at 0 DEG C~25 DEG C, stands 12~48 hours,
Crystallite generation is begun within about 12 hours, subsequent crystal is slowly grown, and obtains cefathiamidine aqueous acetonitrile agent compound monocrystalline.Specific
In implementation process, the dwell temperature preferred scope that the cefathiamidine solution of acetonitrile is uniformly sprawled on surface is 5 DEG C~15 DEG C.In one kind
In possible embodiment, the dwell temperature that the cefathiamidine solution of acetonitrile is uniformly sprawled on surface is constant, in specific implementation process
In, it is believed that temperature is constant at a set temperature in set temperature ± 2 DEG C.
The obtained crystal of this method is rhabdolith, as shown in Figure 2；With polarized light property and crystallinity height, such as Fig. 3 institute
Show；The main peak position of XRD be 2 θ=7.311 °, 7.493 °, 8.016 °, 12.078 °, 16.101 °, 20.973 °, 21.457 °,
As shown in Figure 4；Product has obvious weightlessness before 393K, represents the removing of acetonitrile and aqueous solvent, as shown in Figure 5；And it loses
Need to absorb heat when acetonitrile and water, when cefathiamidine molecular scission can heat release, as shown in Figure 6；Infared spectrum is as shown in Figure 7.The party
Method preparation can prepare cefathiamidine aqueous acetonitrile agent compound monocrystalline, and crystalline product has pattern integrity degree height, crystallinity high
The advantages of.
Preparation method provided by the invention can successfully prepare cefathiamidine aqueous acetonitrile agent compound, obtained cefathiamidine
Aqueous acetonitrile agent compound monocrystalline is a kind of novel crystal forms of cefathiamidine, and stability is high, and production method is easy to operate, and obtained list
The advantage that crystalline form looks integrity degree is high, cleanliness is high.
Embodiment 1
In clean beaker intermediate ion water and high-purity cefathiamidine anhydride solid, preparing cefathiamidine mass concentration is
The solution of 1.50g/mL, solution are put into stirring and dissolving in ultrasonic tank, after the water system filter membrane for taking the solution to cross 0.22 μm with syringe
It injects in serum bottle, is to filter the solution by the effect of 0.22 μm of water system filter membrane.By 15 times of deionized water quality used
Acetonitrile cefathiamidine solution surface is slowly spread in by dropper, will be statically placed in after serum bottle closure in 15 DEG C of insulating boxs, 24
Crystal taking-up is analyzed and characterized after hour.It is right using German 1000 CCD single crystal diffractometer of Brooker company Smart
Gained crystal prototype is analyzed, and the results are shown in Table 1~6 and attached drawing 1~7.
Table 1 is crystal data and structure optimization data；
Table 2 is non-hydrogen atom coordinate
Table 3 is bond distance
Table 4 is bond angle (°)；
Table 5 is hydrogen atom coordinates
Table 6 is the peak position XRD coordinate.
Crystal be it is colorless and transparent rodlike, using German 1000 CCD single crystal diffractometer of Brooker company Smart, use warp
Graphite monochromatised Cu K alpha ray (λ=0.154184nm) is crossed to be analyzed.Minimum deflection factor R1=0.0499, wR2=
0.1371.The crystal is monocrystalline, belongs to rhombic system, space group P212121, cell parameter Unit cell volumeContain 2 molecule cephalos in each structure cell
Sulphur amidine, 4 molecule acetonitriles and 2 molecular waters.Relative molecular mass is 1145.39, density 1.266g/cm3.Specific data and fitting
Structure cell figure is shown in Table 1~6 and attached drawing 1~7.
Embodiment 2
In clean beaker intermediate ion water and high-purity cefathiamidine anhydride solid, preparing cefathiamidine mass concentration is
The solution of 0.50g/mL, solution are put into stirring and dissolving in ultrasonic tank, after the water system filter membrane for taking the solution to cross 0.22 μm with syringe
It injects in serum bottle.15 times of deionized water quality of acetonitrile used is slowly spread in into cefathiamidine solution surface by dropper,
It will be statically placed in after serum bottle closure in 15 DEG C of insulating boxs, crystal taking-up analyzed and characterized after 24 hours.To gained crystal
Sample is analyzed, as the result is shown: obtained crystal is identical as the crystal type that embodiment 1 obtains.
Embodiment 3
In clean beaker intermediate ion water and high-purity cefathiamidine anhydride solid, preparing cefathiamidine mass concentration is
The solution of 1.00g/mL, solution are put into stirring and dissolving in ultrasonic tank, after the water system filter membrane for taking the solution to cross 0.22 μm with syringe
It injects in serum bottle.15 times of deionized water quality of acetonitrile used is slowly spread in into cefathiamidine solution surface by dropper,
It will be statically placed in after serum bottle closure in 15 DEG C of insulating boxs, crystal taking-up analyzed and characterized after 24 hours.To gained crystal
Sample is analyzed, as the result is shown: obtained crystal is identical as the crystal type that embodiment 1 obtains.
Embodiment 4
In clean beaker intermediate ion water and high-purity cefathiamidine anhydride solid, preparing cefathiamidine mass concentration is
The solution of 1.50g/mL, solution are put into stirring and dissolving in ultrasonic tank, after the water system filter membrane for taking the solution to cross 0.22 μm with syringe
It injects in serum bottle.15 times of deionized water quality of acetonitrile used is slowly spread in into cefathiamidine solution surface by dropper,
It will be statically placed in after serum bottle closure in 15 DEG C of insulating boxs, crystal taking-up analyzed and characterized after 24 hours.To gained crystal
Sample is analyzed, as the result is shown: obtained crystal is identical as the crystal type that embodiment 1 obtains.
Embodiment 5
In clean beaker intermediate ion water and high-purity cefathiamidine anhydride solid, preparing cefathiamidine mass concentration is
The solution of 2.00g/mL, solution are put into stirring and dissolving in ultrasonic tank, after the water system filter membrane for taking the solution to cross 0.22 μm with syringe
It injects in serum bottle.15 times of deionized water quality of acetonitrile used is slowly spread in into cefathiamidine solution surface by dropper,
It will be statically placed in after serum bottle closure in 15 DEG C of insulating boxs, crystal taking-up analyzed and characterized after 24 hours.To gained crystal
Sample is analyzed, as the result is shown: obtained crystal is identical as the crystal type that embodiment 1 obtains.
Embodiment 6
In clean beaker intermediate ion water and high-purity cefathiamidine anhydride solid, preparing cefathiamidine mass concentration is
The solution of 1.50g/mL, solution are put into stirring and dissolving in ultrasonic tank, after the water system filter membrane for taking the solution to cross 0.22 μm with syringe
It injects in serum bottle.10 times of deionized water quality of acetonitrile used is slowly spread in into cefathiamidine solution surface by dropper,
It will be statically placed in after serum bottle closure in 15 DEG C of insulating boxs, crystal taking-up analyzed and characterized after 24 hours.To gained crystal
Sample is analyzed, as the result is shown: obtained crystal is identical as the crystal type that embodiment 1 obtains.
Embodiment 7
In clean beaker intermediate ion water and high-purity cefathiamidine anhydride solid, preparing cefathiamidine mass concentration is
The solution of 1.50g/mL, solution are put into stirring and dissolving in ultrasonic tank, after the water system filter membrane for taking the solution to cross 0.22 μm with syringe
It injects in serum bottle.20 times of deionized water quality of acetonitrile used is slowly spread in into cefathiamidine solution surface by dropper,
It will be statically placed in after serum bottle closure in 15 DEG C of insulating boxs, crystal taking-up analyzed and characterized after 24 hours.To gained crystal
Sample is analyzed, as the result is shown: obtained crystal is identical as the crystal type that embodiment 1 obtains.
Embodiment 8
In clean beaker intermediate ion water and high-purity cefathiamidine anhydride solid, preparing cefathiamidine mass concentration is
The solution of 1.50g/mL, solution are put into stirring and dissolving in ultrasonic tank, after the water system filter membrane for taking the solution to cross 0.22 μm with syringe
It injects in serum bottle.25 times of deionized water quality of acetonitrile used is slowly spread in into cefathiamidine solution surface by dropper,
It will be statically placed in after serum bottle closure in 15 DEG C of insulating boxs, crystal taking-up analyzed and characterized after 24 hours.To gained crystal
Sample is analyzed, as the result is shown: obtained crystal is identical as the crystal type that embodiment 1 obtains.
Embodiment 9
In clean beaker intermediate ion water and high-purity cefathiamidine anhydride solid, preparing cefathiamidine mass concentration is
The solution of 1.50g/mL, solution are put into stirring and dissolving in ultrasonic tank, after the water system filter membrane for taking the solution to cross 0.22 μm with syringe
It injects in serum bottle.30 times of deionized water quality of acetonitrile used is slowly spread in into cefathiamidine solution surface by dropper,
It will be statically placed in after serum bottle closure in 15 DEG C of insulating boxs, crystal taking-up analyzed and characterized after 24 hours.To gained crystal
Sample is analyzed, as the result is shown: obtained crystal is identical as the crystal type that embodiment 1 obtains.
Embodiment 10
In clean beaker intermediate ion water and high-purity cefathiamidine anhydride solid, preparing cefathiamidine mass concentration is
The solution of 1.50g/mL, solution are put into stirring and dissolving in ultrasonic tank, after the water system filter membrane for taking the solution to cross 0.22 μm with syringe
It injects in serum bottle.15 times of acetonitriles of deionized water quality used are slowly spread in into cefathiamidine solution surface by dropper, it will
It is statically placed in after serum bottle closure in 0 DEG C of insulating box, crystal taking-up is analyzed and characterized after 24 hours.To gained crystal prototype
It is analyzed, as the result is shown: obtained crystal is identical as the crystal type that embodiment 1 obtains.
Embodiment 11
In clean beaker intermediate ion water and high-purity cefathiamidine anhydride solid, preparing cefathiamidine mass concentration is
The solution of 1.50g/mL, solution are put into stirring and dissolving in ultrasonic tank, after the water system filter membrane for taking the solution to cross 0.22 μm with syringe
It injects in serum bottle.15 times of deionized water quality of acetonitrile used is slowly spread in into cefathiamidine solution surface by dropper,
It will be statically placed in after serum bottle closure in 5 DEG C of insulating boxs, crystal taking-up analyzed and characterized after 24 hours.To gained crystalloids
Product are analyzed, as the result is shown: obtained crystal is identical as the crystal type that embodiment 1 obtains.
Embodiment 12
In clean beaker intermediate ion water and high-purity cefathiamidine anhydride solid, preparing cefathiamidine mass concentration is
The solution of 1.50g/mL, solution are put into stirring and dissolving in ultrasonic tank, after the water system filter membrane for taking the solution to cross 0.22 μm with syringe
It injects in serum bottle.15 times of deionized water quality of acetonitrile used is slowly spread in into cefathiamidine solution surface by dropper,
It will be statically placed in after serum bottle closure in 10 DEG C of insulating boxs, crystal taking-up analyzed and characterized after 24 hours.To gained crystal
Sample is analyzed, as the result is shown: obtained crystal is identical as the crystal type that embodiment 1 obtains.
Embodiment 13
In clean beaker intermediate ion water and high-purity cefathiamidine anhydride solid, preparing cefathiamidine mass concentration is
The solution of 1.50g/mL, solution are put into stirring and dissolving in ultrasonic tank, after the water system filter membrane for taking the solution to cross 0.22 μm with syringe
It injects in serum bottle.15 times of deionized water quality of acetonitrile used is slowly spread in into cefathiamidine solution surface by dropper,
It will be statically placed in after serum bottle closure in 25 DEG C of insulating boxs, crystal taking-up analyzed and characterized after 24 hours.To gained crystal
Sample is analyzed, as the result is shown: obtained crystal is identical as the crystal type that embodiment 1 obtains.
1 crystal data of table and structure optimization data
2 non-hydrogen atom coordinate of table
3 bond distance of table
4 bond angle (°) of table
5 hydrogen atom coordinates of table
The peak position table 6XRD coordinate
Same and similar part may refer to each other between each embodiment in this specification.
Those skilled in the art will readily occur to of the invention its after considering specification and the disclosure invented here of practice
Its embodiment.This application is intended to cover any variations, uses, or adaptations of the invention, these modifications, purposes or
Person's adaptive change follows general principle of the invention and including the undocumented common knowledge in the art of the present invention
Or conventional techniques.The description and examples are only to be considered as illustrative, and true scope and spirit of the invention are by following
Claim is pointed out.
Invention described above embodiment is not intended to limit the scope of the present invention..
Claims (9)
1. a kind of cefathiamidine aqueous acetonitrile agent compound monocrystalline, which is characterized in that
The monocrystalline is colorless and transparent rhabdolith, belongs to rhombic system, space group P212121, cell parameterUnit cell volumeIn each structure cell
Contain 2 molecule cefathiamidines, 4 molecule acetonitriles and 2 molecular waters.
2. cefathiamidine aqueous acetonitrile agent compound monocrystalline as described in claim 1, which is characterized in that the molecule of the monocrystalline
Formula: C46H72N12O14S4, molecular structural formula are as follows:
3. a kind of preparation method of cefathiamidine aqueous acetonitrile agent compound monocrystalline, which is characterized in that the described method includes:
Step 1: it is molten that cefathiamidine solid and deionized water are configured to the cefathiamidine that mass concentration is 0.10~2.00g/mL
Liquid；
Step 2: being slowly added dropwise acetonitrile in Xiang Suoshu cefathiamidine solution, so that acetonitrile uniformly spreads over the surface of the solution；
Step 3: it is that standing 12~48 is small at 0 DEG C~25 DEG C that the cefathiamidine solution that surface is uniformly sprawled to acetonitrile, which is placed on temperature,
When, obtain cefathiamidine aqueous acetonitrile agent compound monocrystalline.
4. preparation method as claimed in claim 3, which is characterized in that the mass concentration of cefathiamidine solution is in step 1
0.50~1.50g/mL.
5. preparation method as claimed in claim 3, which is characterized in that the quality for the acetonitrile being added dropwise in step 2 is the cephalo
10~30 times of deionized water quality in sulphur amidine solution.
6. preparation method as claimed in claim 5, which is characterized in that the quality for the acetonitrile being added dropwise in step 2 is the cephalo
15~25 times of deionized water quality in sulphur amidine solution.
7. preparation method as claimed in claim 3, which is characterized in that the time of repose in step 3 is 24 hours.
8. preparation method as claimed in claim 3, which is characterized in that the dwell temperature in step 3 is 5 DEG C~15 DEG C.
9. preparation method as claimed in claim 3, which is characterized in that the dwell temperature in step 3 is constant.
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| CN202010049036.4A CN111087411A (en) | 2019-01-30 | 2020-01-16 | Cefathiamidine acetonitrile hydrosolvent single crystal and preparation method thereof |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101074235A (en) * | 2006-05-15 | 2007-11-21 | 中国药品生物制品检定所 | Cephalo-sulfide alcohol hydro-compound and its production |
| CN104530082A (en) * | 2014-12-08 | 2015-04-22 | 悦康药业集团有限公司 | Cefathiamidine compound |
| CN104910186A (en) * | 2015-05-12 | 2015-09-16 | 山东罗欣药业集团股份有限公司 | Cefathiamidine compound |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101074235A (en) * | 2006-05-15 | 2007-11-21 | 中国药品生物制品检定所 | Cephalo-sulfide alcohol hydro-compound and its production |
| CN104530082A (en) * | 2014-12-08 | 2015-04-22 | 悦康药业集团有限公司 | Cefathiamidine compound |
| CN104910186A (en) * | 2015-05-12 | 2015-09-16 | 山东罗欣药业集团股份有限公司 | Cefathiamidine compound |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111087411A (en) * | 2019-01-30 | 2020-05-01 | 山东省分析测试中心 | Cefathiamidine acetonitrile hydrosolvent single crystal and preparation method thereof |
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| CN111087411A (en) | 2020-05-01 |
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