CN103288893B - Clindamycin Phosphate dimethyl sulfoxide solvent compound crystal and preparation method - Google Patents
Clindamycin Phosphate dimethyl sulfoxide solvent compound crystal and preparation method Download PDFInfo
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- CN103288893B CN103288893B CN201310222138.1A CN201310222138A CN103288893B CN 103288893 B CN103288893 B CN 103288893B CN 201310222138 A CN201310222138 A CN 201310222138A CN 103288893 B CN103288893 B CN 103288893B
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- clindamycin phosphate
- dimethyl sulfoxide
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- sulfoxide solvent
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Abstract
The invention provides Clindamycin Phosphate dimethyl sulfoxide solvent compound crystal and preparation method.Crystal is Clindamycin Phosphate dimethyl sulfoxide solvent compound crystal.1 molecule Clindamycin Phosphate, 1 molecule dimethyl sulfoxide (DMSO) is comprised in 1 molecule Clindamycin Phosphate dimethyl sulfoxide solvent compound crystal.Be dissolved in by crude product Clindamycin Phosphate in the mixed solvent of deionized water and dimethyl sulfoxide (DMSO), the volumetric concentration of initial Clindamycin Phosphate is 0.05-0.08g/mL.By solution heated and stirred to lower dissolving, heat filtering, filtrate is placed on slow evaporation in room temperature environment, to there is white crystalline solid, filters to obtain Clindamycin Phosphate dimethyl sulfoxide solvent compound crystal.The stability of Clindamycin Phosphate dimethyl sulfoxide solvent compound is good, places 10 days, crystalchecked at high temperature 60 DEG C, and crystal color keeps white powder, and considerable change does not occur X-ray diffracting spectrum.
Description
Technical field
The invention belongs to medical art, 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-trans-4-propyl group-L-2-pyrrolidine formamido)-1-sulfo--7(S)-pungent the pyranoside of chloro-6,7,8-tri-deoxidation-L-Su Shi-α-D-gala-2-phosphoric acid ester.Go on the market in China from nineteen sixty, Clindamycin Phosphate is the clindamycin derivative of molecular design, external without anti-microbial activity, enters in body and is hydrolyzed into rapidly clindamycin performance pharmacological action.Clindamycin Phosphate antimicrobial spectrum is identical with clindamycin with anti-microbial activity, has anti-microbial activity to the gram-positive microorganisms such as streptococcus aureus, streptococcus pneumoniae and Hemolytic streptococcus and most anerobe.
Clindamycin Phosphate is lactone compound, easily degrades in water, and its aquatic products thing toxicity is large simultaneously, and structure and the pharmacological properties of many degraded products it be unclear that, and affect clinical drug safety.Stability and security are also not ideal enough, affect clinical application.European Pharmacopoeia (EUROPEAN PHARMACOPOEIA5.0,1319-1320) describes this medicine and has polymorphic.Chinese patent CN101838298A reports n-butanol-water solvated compounds crystal and the Clindamycin Phosphate dimethyl sulfoxide (DMSO)-water solvent compound of Clindamycin Phosphate, obtains a kind of the solvate containing dimethyl sulfoxide (DMSO) molecule on this basis.
Summary of the invention
The object of the invention is to the solvated compounds crystal formation studying Clindamycin Phosphate, provide the crystallization method of the novel solvent compound of Clindamycin Phosphate.
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 1 molecule Clindamycin Phosphate dimethyl sulfoxide solvent compound crystal.Molecular formula is: [C
18h
34clN
2o
8pS] C
2h
6oS
Have employed monocrystalline to Clindamycin Phosphate dimethyl sulfoxide solvent compound crystal to characterize, result is as follows:
Crystallographic system: oblique system,
Spacer: P2
1,
Monocrystalline cell parameter:
α=90.00°，β=109.45（3）°，γ=90.00°；
Unit-cell volume:
Molecule number in born of the same parents: Z=2;
Asymmetric cell number: Z '=0.
The monocrystalline molecular structural formula of Clindamycin Phosphate dimethyl sulfoxide solvent compound crystal of the present invention is shown in Fig. 1.
Clindamycin Phosphate dimethyl sulfoxide solvent compound crystal of the present invention, uses Cu-K
aradiation, has characteristic peak with the X-ray powder diffraction that 2 θ angles represent 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 restriction, Clindamycin Phosphate dimethyl sulfoxide solvent compound crystal of the present invention, uses Cu-K
aradiation, the X-ray powder diffraction represented 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 have characteristic peak.
The X-ray powder diffraction of Clindamycin Phosphate dimethyl sulfoxide solvent compound crystal of the present invention is shown in Fig. 2.
Fig. 3 is shown in by the differential thermal analysis collection of illustrative plates of Clindamycin Phosphate dimethyl sulfoxide solvent compound crystal of the present invention.
Fig. 4 is shown in by the thermogravimetric analysis collection of illustrative plates of Clindamycin Phosphate dimethyl sulfoxide solvent compound crystal of the present invention.
The crystallization method of Clindamycin Phosphate dimethyl sulfoxide solvent compound crystal of the present invention, it is characterized in that, be dissolved in by crude product Clindamycin Phosphate in the mixed solvent of deionized water and dimethyl sulfoxide (DMSO), the volumetric concentration of initial Clindamycin Phosphate is 0.05-0.08g/mL.By solution heated and stirred to lower dissolving, heat filtering, filtrate is placed on (envrionment temperature about 25 DEG C) slow evaporation in room temperature environment, to there is white crystalline solid, filters to obtain Clindamycin Phosphate dimethyl sulfoxide solvent compound crystal.
In above-mentioned preparation method, the volume ratio of dimethyl sulfoxide (DMSO) and deionized water is 1:1 ~ 1:5.
The stability of the present inventor to Clindamycin Phosphate dimethyl sulfoxide solvent compound crystal is studied, its effect is that the stability of the Clindamycin Phosphate dimethyl sulfoxide solvent compound obtained is good, and the utilization for Clindamycin Phosphate medicine provides a kind of new crystal and preparation method.
Experimental example: Clindamycin Phosphate dimethyl sulfoxide solvent compound crystalchecked Journal of Sex Research
Investigation condition: Clindamycin Phosphate dimethyl sulfoxide solvent compound crystal is placed on lower 10 days of high temperature 60 DEG C of conditions by hot conditions, respectively at the 5th day and the 10th day sampling and measuring X-ray powder diffraction, judges the stable case of crystal.
The X-ray diffracting spectrum of the Clindamycin Phosphate dimethyl sulfoxide solvent compound stability that this experiment obtains is shown in Fig. 5.
Experimental result shows: place 10 days at high temperature 60 DEG C, Clindamycin Phosphate dimethyl sulfoxide solvent compound crystalchecked, and crystal color keeps white powder, and considerable change does not occur X-ray diffracting spectrum.
Accompanying drawing explanation
Fig. 1 is Clindamycin Phosphate dimethyl sulfoxide solvent compound crystal monocrystalline molecular structure.
Fig. 2 is the powder x-ray diffraction figure that Clindamycin Phosphate dimethyl sulfoxide (DMSO)-water solvates utilizes monochromator to obtain.Length axis represents diffracted intensity (Intensity), and axis of abscissa represents diffraction angle (2 θ).
Fig. 3 is the differential thermal analysis collection of illustrative plates of Clindamycin Phosphate dimethyl sulfoxide solvent compound.
Fig. 4 is the thermogravimetric analysis collection of illustrative plates of Clindamycin Phosphate dimethyl sulfoxide solvent compound.
Fig. 5 is the high-temperature stability experimental result of Clindamycin Phosphate dimethyl sulfoxide solvent compound.
Embodiment
Below by the embodiment by embodiment form, foregoing of the present invention is described in further detail.But this should be interpreted as that the scope of the above-mentioned theme of the present invention is only limitted to following examples.All technology realized 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 solvates
5g Clindamycin Phosphate is dissolved in the mixed solvent of 30mL water and 30mL dimethyl sulfoxide (DMSO) by embodiment 1., then be warming up to 60 DEG C molten clear after, heat filtering, filtrate is placed on (temperature is about 25 DEG C) slow evaporation in room temperature environment, there is long quadrangular shape crystalline solid after 6 days, obtain Clindamycin Phosphate dimethyl sulfoxide solvent compound crystal.The powder diffraction spectrum of product is consistent with Fig. 2.
4g Clindamycin Phosphate is dissolved in the mixed solvent of 20mL water and 40mL dimethyl sulfoxide (DMSO) by embodiment 2., then be warming up to 65 DEG C molten clear after, heat filtering, filtrate is placed on slow evaporation in room temperature environment, there is long quadrangular shape crystalline solid after 7 days, obtain Clindamycin Phosphate dimethyl sulfoxide solvent compound crystal.The powder diffraction spectrum of product is consistent with Fig. 2.
3g Clindamycin Phosphate is dissolved in the mixed solvent of 10mL water and 50mL dimethyl sulfoxide (DMSO) by embodiment 3., then be warming up to 70 DEG C molten clear after, heat filtering, filtrate is placed on slow evaporation in room temperature environment, there is long quadrangular shape crystalline solid after 6 days, obtain Clindamycin Phosphate dimethyl sulfoxide solvent compound crystal.The powder diffraction spectrum of product is consistent with Fig. 2.
Claims (2)
1. a Clindamycin Phosphate dimethyl sulfoxide solvent compound crystal, is characterized in that monocrystalline characterizes as follows:
Crystallographic system: oblique system,
Spacer: P2
1,
Monocrystalline cell parameter:
α＝90.00°，β＝109.45(3)°，γ＝90.00°；
Unit-cell volume:
Molecule number in born of the same parents: Z=2;
Asymmetric cell number: Z '=0.
2. crystal as claimed in claim 1, is characterized in that using Cu-K
aradiation, has characteristic peak with the X-ray powder diffraction that 2 θ angles represent 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.
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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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