寡聚核苷酸对茶碱晶型的调节作用

有机晶体多晶型调控的规律研究对于医药、燃料、农药等行业具有重要意义。茶碱是一种甲基嘌呤类似物,具有I、II、III、IV和M 5种多晶型。由于腺嘌呤核苷与茶碱结构具有相似性,研究了腺嘌呤核苷组成的寡聚核苷酸对茶碱溶液结晶过程的影响。结果表明采用寡聚核苷酸d（A₁₀）、d（A₂₀）为添加剂,能够显著影响乙醇-水体系降温结晶过程中茶碱多晶型的形成,促进M晶型生成。分子模拟计算揭示了腺嘌呤碱基组成的核苷酸片段与茶碱M晶型重要晶面之间的相互作用能最强,正是这种强相互作用促进了茶碱结晶过程中M晶型的生长。     

溶液结晶中晶体形态与结构调控

综述了化学因素(溶剂和添加剂等)和工程因素(过饱和度,晶种和搅拌等)对溶液结晶中晶体形态与结构的影响,分析了这些因素会影响溶质分子在溶液主体中的聚集形式及其在晶体界面的扩散和吸附过程,进而影响晶体的成核和生长机理及速率,并由此改变最终产品的形貌和结构。调控结晶工艺参数和优化操作条件可得到目标结晶产物。     

添加剂在药物结晶中的应用研究进展

结晶作为药物分离纯化的主要手段,是制药行业的一种重要的单元操作。在药物结晶过程中,通过添加剂能够直接有效的调控产物的形貌、晶型和粒度。添加剂的加入可以调控药物晶体的性质。本文主要对高分子聚合物、离子液体、低共熔溶剂、小分子化合物等不同种类添加剂在药物结晶中的应用进行总结概括,期望为该领域的研究提供资料支持。     

L-组氨酸和L-色氨酸对L-苯丙氨酸溶解度及晶型转化的影响

采用静态法测定了tailor-made型添加剂L-组氨酸、L-色氨酸对L-苯丙氨酸在水溶剂中溶解度的影响,并应用Apelblat经验方程进行了拟合;此外,文中还展开了tailor-made型添加剂对L-苯丙氨酸晶型转化过程的影响研究,并用Langmuir模型拟合回归。结果表明,L-苯丙氨酸溶解度随温度的升高而增大,且tailor-made型添加剂L-组氨酸、L-色氨酸的加入增大了L-苯丙氨酸在水中的溶解度;并且L-组氨酸、L-色氨酸添加剂的加入均可抑制L-苯丙氨酸向稳定晶型转化,但抑制能力各不相同,Langmuir模型拟合回归结果表明,L-色氨酸的加入可完全抑制L-苯丙氨酸低温环境内无水合物转为一水合物,高温区内一水合物转为无水合物则不能完全抑制;L-组氨酸在低温区和高温区内均不能对L-苯丙氨酸向稳定晶型的转化起到完全抑制作用。     

β-蒿甲醚的多晶型、晶体结构解析与晶习研究

考察了不同结晶方式及条件对蒿甲醚晶型的影响,通过X射线单晶衍射和X射线粉末衍射表征,结合分子动力学模拟,利用直接空间解析方法,对所确定的β-蒿甲醚两种多晶型进行了结构分析。通过热分析考察了两种晶型的热稳定性,采用BFDH模型和AE模型,对β-蒿甲醚A晶型的理论晶习进行了模拟预测。结果表明,β-蒿甲醚两种多晶型的晶胞结构分别为单斜晶系、P21空间群和三斜晶系、P-1空间群,温度会导致β-蒿甲醚多晶型之间的可逆转变,通过模拟获得的A晶型理论晶习与实际生长情况相近。     

聚合物对药物结晶影响研究进展

在溶液结晶过程中,聚合物添加剂通过参与晶体的成核和生长,在控制晶体的晶型、晶体尺寸和形态方面具有显著的效果。综述了聚合物在药物结晶抑制和调控两方面的研究进展。聚合物分子可以吸附在生长表面,通过阻碍溶质分子在晶体上的聚集来抑制晶体生长。聚合物分子还可以使晶体生长机理发生改变,从而对药物的晶型进行调控。并对未来的发展和前景进行了展望。     

多种晶型纳米碳酸钙制备及生长机理的研究进展

纳米碳酸钙作为一种通用材料,具有广泛的应用前景和市场需求,近年来备受关注。然而,由于纳米碳酸钙晶型的多样性,导致其在不同领域具备不同的应用潜力。因此,对不同晶型纳米碳酸钙的制备方法、生长影响因素及形成机制进行了深入研究,并且有目标地制备特定晶型产品已成为当前研究的焦点。首先概述了纳米碳酸钙结构,并总结了两种常见制备方法的优缺点和机理;其次重点阐述了晶型控制剂和制备工艺对纳米碳酸钙晶型调控方面的研究进展,并介绍了两种反应器能够增强溶液间微观混合效果,从而大幅提高整体反应效率;最后综述了纳米碳酸钙结晶过程同时受晶体成核和晶体生长共同控制。通过研究这两个结晶过程可以更好地理解内在机理,最终实现晶型和形貌的精确调控。     

溶剂和结晶温度对尼龙12多晶型的影响

结晶温度和溶剂影响尼龙12晶型。将尼龙12溶于不同溶剂中，将其浇铸成膜并等温结晶，运用广角X射线衍射、差示扫描量热(DSC)法和傅里叶变换红外光谱研究了溶剂和结晶温度对尼龙12多晶型的影响。结果表明，以苯酚/甲酸(v/v=1/1)为溶剂时，室温结晶生成α晶；80℃及以上温度得到γ晶；40～70℃时，α晶与γ晶共存，但α晶含量随着结晶温度的升高而逐渐减少。以甲酸/二氯甲烷(v/v=1/1)为溶剂时，室温结晶得到α晶白色不透明粉末，60℃时却得到γ晶半透明薄膜。DSC结果表明，结晶温度越高，形成的α晶熔点越高，且部分α晶在升温过程中Brill转变为γ晶。尼龙12从甲酸/二氯甲烷溶液结晶所得α晶和γ晶的峰值熔融温度分别高于从苯酚/甲酸溶液所得样品的峰值熔融温度。     

添加剂对氨基酸晶体生长的影响

氨基酸大多生长为针状或片状晶习,存在堆密度低、流动性差等问题,严重影响产品后加工处理过程。因此,实现氨基酸晶习的定向调控具有重要意义。添加剂对氨基酸晶习调控直接有效,广泛应用于工业生产中。本文主要从抑制和促进晶体生长两个角度,综述了添加剂对氨基酸晶体生长的作用机理。添加剂对晶体生长的抑制机理主要有两点：一是添加剂分子吸附到晶面上,阻碍溶质分子的扩散和聚集;二是添加剂分子嵌入晶格并占据生长位点。而添加剂促进晶体生长的机理为：添加剂加快了溶质分子在晶体表面的聚集速度、使晶体表面粗糙化和降低了溶剂层脱除能垒。最后,针对添加剂对氨基酸晶体生长影响的研究,从晶体工程的角度提出了通过分子模拟设计的添加剂定向控制氨基酸晶体生长,从而调控晶习的展望。     

小分子药物多晶型调控研究进展

综述了近年来小分子药物多晶型的调控方法及因素,简单介绍了药物多晶型的概念与分类,在此基础上重点探讨了影响药物多晶型成核的溶液初级因素(过饱和度、溶剂、温度、流场与晶种等)与外来模板表面因素(表面外延、表面形貌与表面化学等),并结合溶液因素与模板因素对小分子药物多晶型调控进行了总结与展望.     

Tailor-made additives to influence the habit of barite (BaSO4) obtained by precipitation

In order to influence the habit of barite (BaSO₄) single crystals obtained by precipitation, the tailor-made additives 2-aminomethanol, 3-aminoproponal, 5-aminopentanol, 4-aminobutane sulfonic acid, and several other growth inhibitors have been tested. The crystallization experiments have been carried out in a fully automated crystallizer with reproducible educt feed rates. The kinetics of the reaction has been measured by means of the conductivity. Scanning electron microscopic analysis of the obtained crystal habits led to the raesult that most of the additives tested did not influence the growth form of the crystals, but the predicted, tailor-made additives resulted in a more isometric crystal form.     

晶型控制剂对沉淀碳酸钙晶型、形态的影响

碳酸钙是一种重要的无机化工产品，不同晶型、形态的碳酸钙有着不同的用途。晶型控制剂的加入在改变沉淀碳酸钙的晶型、形态方面都有着重要的作用。介绍了国内外在制备沉淀碳酸钙过程中，已经使用以及正在研究的各种晶型控制剂。总结了一些晶型控制剂的加入对沉淀碳酸钙晶型、形态所产生的影响，并且根据晶型控制剂类型的不同对其作用原理进行了解释。     

Effect of Ultrasonic Irradiation on the Probability of Primary Nucleation of L-Arginine Hydrochloride

Most of the amino acids that are utilized as medical raw materials and food additives show polymorphism. To improve the functionality of amino acid crystals, an effective method of polymorph control is required in the crystallization process. Here, primary nucleation of L-arginine hydrochloride by ultrasonication was investigated. L-Arginine hydrochloride exhibits polymorphism, and it crystallizes into three distinct crystal forms. A cooling crystallization experiment was performed, and nucleation of each polymorph upon ultrasonication was observed. In addition, the nucleation was analyzed using the nucleation probability theory. The results indicate that ultrasonic irradiation would significantly induce the nucleation of a particular polymorph.     

Process control and monitoring of reactive crystallization of L‐glutamic acid

The aim of the present study was to investigate feedback control of a reactive crystallization process. The present study built up a control structure needed to control the driving force of reactive crystallization using the feed rate of added acid. The concentration of the crystallizing compound and pH was used to compute feedback in the closed‐loop control of semi‐batch precipitation. The concentration of L ‐glutamic acid was determined from measured MID‐IR ATR‐FTIR spectra based on a multivariate model. Dynamic change of set value was based on the mass of added sulfuric acid and pH. The studied properties of the product crystals were polymorphism and crystal size. The polymorphic composition was analyzed with a Raman spectrometer and was expressed by mass fraction of the α‐polymorph. The obtained results showed that the developed feedback process control system allows effective control of forming of polymorphs. © 2009 American Institute of Chemical Engineers AIChE J, 2010     

球形氯化钾结晶过程与聚结机理研究

针对球形氯化钾结晶过程与聚结机理不明的问题,以冷却结晶法通过过程取样制备与表征了两种不同形貌的氯化钾在不同结晶阶段的晶体形貌与粒度分布特征,从而对比分析了球形氯化钾的结晶过程。并从结晶热力学、经典浸润理论和Lifshitz-Van der Waals酸碱理论出发解释了球形氯化钾形成的主要机理是添加剂的添加减小了结晶体系的介稳区宽度及增大了晶体颗粒在结晶溶剂中的粘附自由能,导致结晶体系更容易以聚结的方式实现球形结晶。介稳区宽度减小和晶体颗粒在结晶溶剂中粘附自由能增大的同步调控有助于实现氯化钾的球形结晶。     

Biomineralization of calcium carbonate by adding aspartic acid and lysozyme

Calcium carbonate is one of the most abundant materials present in nature. Crystal structures of CaCO₃ become three polymorphic modifications, namely calcite, aragonite and vaterite. Polymorphic modifications are mediated by adding aspartic acid (Asp) and lysozyme. Lysozyme, which is a major component of egg white proteins, has influenced the calcification of avian eggshells. The influence of Asp and lysozyme on the crystallization of CaCO₃ was investigated by adding these additives and calcium chloride solution into sodium carbonate solution in a crystallization vessel. CaCO₃ crystals were analyzed by X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM) and Fourier transform infrared spectrometry (FT-IR). XRD was used to select the intensities and crystal structure of specific calcium carbonate. SEM was employed for the analysis of the morphology of the precipitation and particle size. Two kinds of crystals were identified by FT-IR spectrum. Hexagonal crystals of vaterite were affected by the Asp in the crystallization solution. However, rhombohedral crystals of calcite by lysozyme were formed without any sign of vaterite.     

High‐order simulation of polymorphic crystallization using weighted essentially nonoscillatory methods

Most pharmaceutical manufacturing processes include a series of crystallization processes to increase purity with the last crystallization used to produce crystals of desired size, shape, and crystal form. The fact that different crystal forms (known as polymorphs) can have vastly different characteristics has motivated efforts to understand, simulate, and control polymorphic crystallization processes. This article proposes the use of weighted essentially nonoscillatory (WENO) methods for the numerical simulation of population balance models (PBMs) for crystallization processes, which provide much higher order accuracy than previously considered methods for simulating PBMs, and also excellent accuracy for sharp or discontinuous distributions. Three different WENO methods are shown to provide substantial reductions in numerical diffusion or dispersion compared with the other finite difference and finite volume methods described in the literature for solving PBMs, in an application to the polymorphic crystallization of L ‐glutamic acid. © 2008 American Institute of Chemical Engineers AIChE J, 2009     

Additives effects on crystallization and morphology in a novel caustic aluminate solution decomposition process

A novel process of caustic aluminate solution decomposition by alcohol medium was developed by the Institute of Process Engineering, Chinese Academy of Sciences in order to solve the problem of low decomposition ratio in the traditional Bayer seeded hydrolysis process. In this research, effects of additives on the crystallization ratio, secondary particle size and morphology of aluminum hydroxide in the new process were studied to obtain high-quality products. On the basis of primary selection of additives, an orthogonal design L9(3⁴) was used as a chemometric method to investigate the effects of additives. The studied parameters include the reaction style, quantity of additives, caustic soda concentration, as well as the combination manner. The crystallization ratios of sodium aluminate solution and crystal size of aluminum hydroxide, determined by ICP-OES, SEM and MLPSA (Malvern Laser Particle Size Analyzer), were used to evaluate the effects of the additives. The results showed that different combination manners could promote agglomeration or dispersion. An additive composed by Tween 80 and PEG 200 could promote agglomeration, while a spot of PEG species had a relatively strong dispersion effect. However, the additives had little effects on the crystallization ratios. According to the Raman spectra result, the added alcohol medium might serve as a kind of solvent.     

Application of quantitative Raman spectroscopy for the monitoring of polymorphic transformation in crystallization processes using a good calibration practice procedure

Polymorphism is the property of a substance to have more than one crystalline form. Polymorphic forms of the same chemical compound can have different physical and chemical properties that can strongly affect the manufacturing process. For this reason, determining and monitoring polymorphic transformations have become very important, especially in pharmaceutical industry. Significant work has been developed for the calibration of Raman spectroscopy to monitor the presence and amount of solid polymorphs in suspensions during crystallization, as well as the liquid concentration. Nevertheless, a clear and systematic approach to Raman calibration is missing in the literature. The present work has the aim of developing a methodical strategy for Raman calibration, taking into account the principal factors that can affect the Raman spectra of a specific compound in solution, such as solid type, solute concentration, temperature, crystal size and suspension density. Univariate and multivariate calibration techniques were investigated using pre-processing techniques to optimize the signal. The results are combined in a systematic “good calibration practice” (GCP) procedure, proposed for the first time in this work. The approach has been applied for the quantitative monitoring of the polymorphic transformation of ortho-aminobenzoic acid (OABA).