【作者】 王福军；

【导师】 王永莉；

【作者基本信息】 天津大学 ， 化学工程与技术， 2004， 硕士

【摘要】 地塞米松磷酸钠是一种重要的肾上腺糖皮质激素类药物，在临床上有十分广泛的应用。目前，国内生产的地塞米松磷酸钠与国外同类产品相比，在粒度、纯度及结晶过程的收率等方面都存在着一定的差距。本论文对地塞米松磷酸钠晶体结构与晶习、结晶热力学和动力学及生产规模的反应－溶析藕合结晶工艺进行了研究与分析，并在此基础上完成了年产60吨地塞米松磷酸钠的藕合结晶过程的设计与生产实施。利用X-射线粉末衍射仪搜集了地塞米松磷酸钠晶体的衍射数据，用TREOR90指标化程序计算得到了地塞米松磷酸钠晶体的晶胞参数及其所属晶系；应用扫描电子显微镜(SEM)观察的方法分析考察了结晶方法、溶剂类型及温度对地塞米松磷酸钠产品晶习的影响。采用激光法测定了地塞米松磷酸钠在各种溶剂中的溶解度并考察了温度和溶剂配比对溶解度的影响情况；测定了地塞米松磷酸钠在甲醇－丙酮－水体系中的结晶介稳区；运用最小二乘法回归得到了溶解度与介稳区的经验数学模型；对地塞米松磷酸钠反应及溶析结晶动力学进行了分析。结合晶体生产习性、热力学和动力学特性以及对实验室研究结果的分析，建立了地塞米松磷酸钠耦合结晶过程优化操作时间表，并成功完成了生产过程的设计放大与实施，产品的各项指标均达到国际水平。本论文所做的有关地塞米松磷酸钠晶体结构、结晶生产新工艺的研究与应用在国内外的文献中尚未见到过任何报道。更多还原

【Abstract】 Dexamethasone sodium phosphate is one kind of important drugs of ardrenal cortex hormone, and it is widely used in clinical application. Up to now, home-made dexamethasone sodium phosphate is not as good as those overseas products in terms of its purity and size etc. In this paper, the crystal structure, crystal habit, crystallization thermodynamics, crystallization kinetics and the plant-scale reaction-dilution coupled crystallization technics of dexamethasone sodium phosphate was studied. The manufacturing process with output of 60 ton/year for dexamethasone sodium phosphate was designed and set up. The diffraction data for dexamethasone sodium phosphate crystal was collected by X-ray diffraction technique. Using the indexing program named TREOR90, the unit cell parameters and space group for dexamethasone sodium phosphate were obtained by the indexing of its diffraction data. The effect of crystallization method, solvent and temperature on crystal habit of dexamethasone sodium phosphate were investigated by SEM(scanning electronics microscope) analysis. The solubility of dexamethasone sodium phosphate in different solvents was determined by laser monitor method. The effect of temperature and solvent on solubility was discussed. Crystallization metastable zone of dexamethasone sodium phosphate in methanol-acetone-water system was determined. The empirical model for solubility and metastabel zone of dexamethasone sodium phosphate was gotten by the least square method. The reaction and dilution crystallization kinetics for dexmethasone sodium phosphate were analyzed. The empirical optimum operation schedule for dexamethasone sodium phosphate coupled crystallization process was established by synthetically considering property of crystal production, thermodynamics, kinetics and experimental study results. The manufacturing process for dexamethasone sodium phosphate was successfully designed and industrialized. The quality of the crystal product is as good as overseas product or better. The work about crystal structure and the crystallization new technics for dexamethasone sodium phosphate, which was done in this paper, has not been reported in any literatures.更多还原