CN103288893A - Clindamycin phosphate dimethyl sulfoxide solvent compound crystal and preparation method thereof - Google Patents
Clindamycin phosphate dimethyl sulfoxide solvent compound crystal and preparation method thereof Download PDFInfo
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- CN103288893A CN103288893A CN2013102221381A CN201310222138A CN103288893A CN 103288893 A CN103288893 A CN 103288893A CN 2013102221381 A CN2013102221381 A CN 2013102221381A CN 201310222138 A CN201310222138 A CN 201310222138A CN 103288893 A CN103288893 A CN 103288893A
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- clindamycin phosphate
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Abstract
The invention provides a clindamycin phosphate dimethyl sulfoxide solvent compound crystal and a preparation method thereof. The crystal is the clindamycin phosphate dimethyl sulfoxide solvent compound crystal; 1 molecule of the clindamycin phosphate dimethyl sulfoxide solvent compound crystal comprises 1 molecule of clindamycin phosphate and 1 molecule of dimethyl sulfoxide. The preparation method comprises the following steps of: dissolving crude clindamycin phosphate into a mixed solvent of deionized water and the dimethyl sulfoxide, wherein the volume concentration of initial clindamycin phosphate is 0.05-0.08 g/mL; heating and stirring a solution till the solution is dissolved, carrying out hot filtration, placing filter liquor in a room temperature environment, and slowly evaporating till white crystalline solids appear; filtering to obtain the clindamycin phosphate dimethyl sulfoxide solvent compound crystal. The clindamycin phosphate dimethyl sulfoxide solvent compound has good stability property; after the clindamycin phosphate dimethyl sulfoxide solvent compound is placed at a high temperature of 60 DEG C for 10 days, the crystal is stable, the crystal is kept as white powder, and an X-ray X-ray diffraction pattern is not obviously changed.
Description
Technical field
The invention belongs to medical technical field, be specifically related to Clindamycin Phosphate novel solvent compound and crystallization method thereof.
Background technology
Clindamycin Phosphate is antibiotics, and its chemical name is: methyl 6-(1-methyl-anti--4-propyl group-L-2-pyrrolidine formamido)-and the 1-sulfo--7(S)-chloro-6,7, the hot pyranoside of 8-three deoxidations-L-Su Shi-α-D-gala-2-phosphoric acid ester.Go on the market in China from nineteen sixty, Clindamycin Phosphate is chemical semisynthetic clindamycin derivative, and external no antibiotic activity enters and is hydrolyzed into clindamycin performance pharmacological action in the body rapidly.The Clindamycin Phosphate antimicrobial spectrum is identical with clindamycin with anti-microbial activity, and gram-positive microorganisms such as streptococcus aureus, streptococcus pneumoniae and Hemolytic streptococcus and most anerobe are had anti-microbial activity.
Clindamycin Phosphate is lactone compound, easily degraded in water, and its aquatic products thing toxicity is big simultaneously, and structure and the pharmacological properties of many degraded products it be unclear that, and influence clinical drug safety.Stability and security are also not ideal enough, influence clinical application.(EUROPEAN PHARMACOPOEIA5.0 1319-1320) describes this medicine and has polymorphic European Pharmacopoeia.Chinese patent CN101838298A has reported n-butanol-water solvated compounds crystal and the Clindamycin Phosphate dimethyl sulfoxide (DMSO)-water solvent compound of Clindamycin Phosphate, has obtained a kind of solvate that contains the dimethyl sulfoxide (DMSO) molecule on this basis.
Summary of the invention
The objective of the invention is to study the solvated compounds crystal formation of Clindamycin Phosphate, the crystallization method of the novel solvent compound of Clindamycin Phosphate is provided.
The invention provides solvated compounds crystalline structure and the crystallization method thereof of Clindamycin Phosphate.
The solvated compounds crystalline structure crystal of Clindamycin Phosphate is Clindamycin Phosphate dimethyl sulfoxide solvent compound crystal.
Wherein comprise 1 molecule Clindamycin Phosphate, 1 molecule dimethyl sulfoxide (DMSO) in the 1 molecule Clindamycin Phosphate dimethyl sulfoxide solvent thing crystal.Molecular formula is: [C
18H
34ClN
2O
8PS] C
2H
6OS
To Clindamycin Phosphate dimethyl sulfoxide solvent thing crystal by adopting the monocrystalline sign, the result is as follows:
Crystallographic system: oblique system,
Spacer: P2
1,
The monocrystalline cell parameter:
α=90.00°，β=109.45（3）°，γ=90.00°；
Unit-cell volume:
Molecule number: Z=2 in the born of the same parents;
Asymmetric cell number: Z '=0.
The monocrystalline molecular structural formula of Clindamycin Phosphate dimethyl sulfoxide solvent compound crystal of the present invention is seen Fig. 1.
Clindamycin Phosphate dimethyl sulfoxide solvent compound crystal of the present invention uses Cu-K
aRadiation, the X-ray powder diffraction of representing with 2 θ angles has characteristic peak 6.5 ± 0.1,12.6 ± 0.1,13.0 ± 0.1,15.7 ± 0.1,19.1 ± 0.1,20.1 ± 0.1,20.4 ± 0.1,22.9 ± 0.1,23.5 ± 0.1,26.2 ± 0.1.
Further limit, Clindamycin Phosphate dimethyl sulfoxide solvent compound crystal of the present invention uses Cu-K
aRadiation, the X-ray powder diffraction of representing with 2 θ angles is 6.5 ± 0.1,7.7 ± 0.1,12.6 ± 0.1,13.0 ± 0.1,13.6 ± 0.1,15.7 ± 0.1,17.3 ± 0.1,17.7 ± 0.1,18.5 ± 0.1,19.1 ± 0.1,19.6 ± 0.1,20.1 ± 0.1,20.4 ± 0.1,21.7 ± 0.1,22.4 ± 0.1,22.7 ± 0.1,22.9 ± 0.1,23.5 ± 0.1,23.9 ± 0.1,24.7 ± 0.1,25.1 ± 0.1,25.6 ± 0.1,25.9 ± 0.1,26.2 ± 0.1,26.5 ± 0.1,27.5 ± 0.1,28.4 ± 0.1,28.7 ± 0.1,29.4 ± 0.1,29.8 ± 0.1,30.2 ± 0.1,30.7 ± 0.1,31.2 ± 0.1,31.6 ± 0.1,32.4 ± 0.1,33.3 ± 0.1,34.1 ± 0.1,34.8 ± 0.1,35.5 ± 0.1,35.9 ± 0.1,36.5 ± 0.1,36.9 ± 0.1,37.4 ± 0.1,37.8 ± 0.1,38.1 ± 0.1,38.9 ± 0.1,39.2 ± 0.1,40.0 ± 0.1,41.0 ± 0.1 has characteristic peak.
The X-ray powder diffraction of Clindamycin Phosphate dimethyl sulfoxide solvent compound crystal of the present invention is seen Fig. 2.
The differential thermal analysis collection of illustrative plates of Clindamycin Phosphate dimethyl sulfoxide solvent compound crystal of the present invention is seen Fig. 3.
The thermogravimetric analysis collection of illustrative plates of Clindamycin Phosphate dimethyl sulfoxide solvent compound crystal of the present invention is seen Fig. 4.
The crystallization method of Clindamycin Phosphate dimethyl sulfoxide solvent compound crystal of the present invention, it is characterized in that, the crude product Clindamycin Phosphate is dissolved in the mixed solvent of deionized water and dimethyl sulfoxide (DMSO), the volumetric concentration of initial Clindamycin Phosphate is 0.05-0.08g/mL.With the solution heated and stirred to down dissolving, heat filtering, filtrate is placed on (about 25 ℃ of envrionment temperatures) slowly evaporation in the room temperature environment, to white crystalline solid occurring, filter Clindamycin Phosphate dimethyl sulfoxide solvent compound crystal.
The volume ratio of dimethyl sulfoxide (DMSO) and deionized water is 1:1～1:5 among the above-mentioned preparation method.
The inventor studies the stability of Clindamycin Phosphate dimethyl sulfoxide solvent thing crystal, its effect is that the stability of the Clindamycin Phosphate dimethyl sulfoxide solvent thing that obtains is good, for the utilization of Clindamycin Phosphate medicine provides a kind of new crystal and preparation method.
Experimental example: Clindamycin Phosphate dimethyl sulfoxide solvent thing crystalchecked Journal of Sex Research
The investigation condition: hot conditions was placed on 60 ℃ of conditions of high temperature following 10 days with Clindamycin Phosphate dimethyl sulfoxide solvent thing crystal, respectively at the 5th day and the 10th day sampling and measuring X-ray powder diffraction, judged the stable case of crystal.
The X-ray diffracting spectrum of the Clindamycin Phosphate dimethyl sulfoxide solvent thing stability that this experiment obtains is seen Fig. 5.
Experimental result shows: placed 10 days down for 60 ℃ at high temperature, and Clindamycin Phosphate dimethyl sulfoxide solvent thing crystalchecked, crystal color keeps white powder, and considerable change does not take place in X-ray diffracting spectrum.
Description of drawings
Fig. 1 is Clindamycin Phosphate dimethyl sulfoxide solvent thing crystal monocrystalline molecular structure.
Fig. 2 is the powder x-ray diffraction figure that the Clindamycin Phosphate dimethyl sulfoxide (DMSO)-water-soluble thinner thing utilizes monochromator to obtain.Length axis is represented diffracted intensity (Intensity), and axis of abscissa is represented diffraction angle (2 θ).
Fig. 3 is the differential thermal analysis collection of illustrative plates of Clindamycin Phosphate dimethyl sulfoxide solvent thing.
Fig. 4 is the thermogravimetric analysis collection of illustrative plates of Clindamycin Phosphate dimethyl sulfoxide solvent thing.
Fig. 5 is the high-temperature stability experimental result of Clindamycin Phosphate dimethyl sulfoxide solvent thing.
Embodiment
Below will foregoing of the present invention be described in further detail by the embodiment of embodiment form.But this should be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following examples.All technology that realizes based on foregoing of the present invention all belong to scope of the present invention.
The preparation of embodiment Clindamycin Phosphate dimethyl sulfoxide (DMSO)-water-soluble thinner thing
Embodiment 1. is dissolved in the 5g Clindamycin Phosphate in the mixed solvent of 30mL water and 30mL dimethyl sulfoxide (DMSO), be warming up to then 60 ℃ molten clear after, heat filtering, filtrate is placed on (temperature is about 25 ℃) slowly evaporation in the room temperature environment, occur long quadrangular shape crystalline solid after 6 days, get Clindamycin Phosphate dimethyl sulfoxide solvent compound crystal.The powder diffraction spectrum of product is consistent with Fig. 2.
Embodiment 2. is dissolved in the 4g Clindamycin Phosphate in the mixed solvent of 20mL water and 40mL dimethyl sulfoxide (DMSO), be warming up to then 65 ℃ molten clear after, heat filtering, filtrate is placed on slowly evaporation in the room temperature environment, occur long quadrangular shape crystalline solid after 7 days, get Clindamycin Phosphate dimethyl sulfoxide solvent compound crystal.The powder diffraction spectrum of product is consistent with Fig. 2.
Embodiment 3. is dissolved in the 3g Clindamycin Phosphate in the mixed solvent of 10mL water and 50mL dimethyl sulfoxide (DMSO), be warming up to then 70 ℃ molten clear after, heat filtering, filtrate is placed on slowly evaporation in the room temperature environment, occur long quadrangular shape crystalline solid after 6 days, get Clindamycin Phosphate dimethyl sulfoxide solvent compound crystal.The powder diffraction spectrum of product is consistent with Fig. 2.
Claims (6)
1. a Clindamycin Phosphate dimethyl sulfoxide solvent compound crystal is characterized in that crystal is Clindamycin Phosphate dimethyl sulfoxide solvent compound crystal.
2. crystal as claimed in claim 1 is characterized in that comprising 1 molecule Clindamycin Phosphate, 1 molecule dimethyl sulfoxide (DMSO) in the 1 molecule Clindamycin Phosphate dimethyl sulfoxide solvent thing crystal.
3. crystal as claimed in claim 1, it is as follows to it is characterized in that monocrystalline characterizes:
Crystallographic system: oblique system,
Spacer: P2
1,
The monocrystalline cell parameter:
α=90.00°，β=109.45（3）°，γ=90.00°；
Unit-cell volume:
Molecule number: Z=2 in the born of the same parents;
Asymmetric cell number: Z '=0.
4. crystal as claimed in claim 1 is characterized in that using Cu-K
aRadiation, the X-ray powder diffraction of representing with 2 θ angles has characteristic peak 6.5 ± 0.1,12.6 ± 0.1,13.0 ± 0.1,15.7 ± 0.1,19.1 ± 0.1,20.1 ± 0.1,20.4 ± 0.1,22.9 ± 0.1,23.5 ± 0.1,26.2 ± 0.1.
5. the preparation method of claim 1,2,3 or 4 described crystal is characterized in that the crude product Clindamycin Phosphate is dissolved in the mixed solvent of deionized water and dimethyl sulfoxide (DMSO), and the volumetric concentration of Clindamycin Phosphate is 0.05-0.08g/mL; With the solution heated and stirred to down dissolving, heat filtering, filtrate is placed on slowly evaporation in the room temperature environment, to white crystalline solid occurring, filter Clindamycin Phosphate dimethyl sulfoxide solvent compound crystal.
6. method as claimed in claim 4, the volume ratio that it is characterized in that dimethyl sulfoxide (DMSO) and deionized water is 1:1～5.
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Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4895934A (en) * | 1988-08-22 | 1990-01-23 | E. I. Du Pont De Nemours And Company | Process for the preparation of clindamycin phosphate |
| US5182374A (en) * | 1990-03-21 | 1993-01-26 | American Cyanamid Company | Clindamycin phosphate synthesis |
| CN1602889A (en) * | 2004-08-27 | 2005-04-06 | 北京国仁堂医药科技发展有限公司 | Preparation method of clindamycin phosphate powder injection |
| WO2008017914A2 (en) * | 2006-08-08 | 2008-02-14 | Fernando Ahumada Ayala | Topical antiacne preparations containing retinoid (tazarotene or adapalene), antibiotic (clindamycin phosphate) and/or keratolytic (miscrosponged benzoyl peroxide) |
| CN101838298A (en) * | 2009-03-16 | 2010-09-22 | 珠海亿邦制药有限公司 | Clindamycin phosphate solvate crystal and preparation method thereof |
| CN101838297A (en) * | 2009-03-16 | 2010-09-22 | 珠海亿邦制药有限公司 | Crystal form of clindamycin phosphate and preparation method thereof |
| CN102690300A (en) * | 2009-03-16 | 2012-09-26 | 珠海亿邦制药股份有限公司 | Clindamycin phosphate solvate crystal and preparation method thereof |
| CN102731585A (en) * | 2012-07-23 | 2012-10-17 | 江西省康华医药科技有限公司 | New active clindamycin phosphate compound and medicinal composition thereof |
| CN102964401A (en) * | 2012-11-20 | 2013-03-13 | 广州白云山天心制药股份有限公司 | Method for preparing clindamycin phosphate |
-
2013
- 2013-06-05 CN CN201310222138.1A patent/CN103288893B/en active Active
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4895934A (en) * | 1988-08-22 | 1990-01-23 | E. I. Du Pont De Nemours And Company | Process for the preparation of clindamycin phosphate |
| US5182374A (en) * | 1990-03-21 | 1993-01-26 | American Cyanamid Company | Clindamycin phosphate synthesis |
| CN1602889A (en) * | 2004-08-27 | 2005-04-06 | 北京国仁堂医药科技发展有限公司 | Preparation method of clindamycin phosphate powder injection |
| WO2008017914A2 (en) * | 2006-08-08 | 2008-02-14 | Fernando Ahumada Ayala | Topical antiacne preparations containing retinoid (tazarotene or adapalene), antibiotic (clindamycin phosphate) and/or keratolytic (miscrosponged benzoyl peroxide) |
| CN101838298A (en) * | 2009-03-16 | 2010-09-22 | 珠海亿邦制药有限公司 | Clindamycin phosphate solvate crystal and preparation method thereof |
| CN101838297A (en) * | 2009-03-16 | 2010-09-22 | 珠海亿邦制药有限公司 | Crystal form of clindamycin phosphate and preparation method thereof |
| CN102690300A (en) * | 2009-03-16 | 2012-09-26 | 珠海亿邦制药股份有限公司 | Clindamycin phosphate solvate crystal and preparation method thereof |
| CN102731585A (en) * | 2012-07-23 | 2012-10-17 | 江西省康华医药科技有限公司 | New active clindamycin phosphate compound and medicinal composition thereof |
| CN102964401A (en) * | 2012-11-20 | 2013-03-13 | 广州白云山天心制药股份有限公司 | Method for preparing clindamycin phosphate |
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