HPLC法测定药物共晶中茶碱和对乙酰氨基酚的研究

建立了高效液相色谱法分离茶碱和对乙酰氨基酚双组分体系的最佳条件是:C18色谱柱(250 mm×4.6 mm,5μm,120),以十八烷基键合硅胶为固定相;流动相为0.01 mol/L磷酸二氢钾溶液(用磷酸溶液调节pH至3.05)(A)-甲醇(B)(体积比为80∶20);检测波长为245 nm和270 nm;流速为1.0 mL/min;柱温为25℃;进样量为20μL。实验结果表明:对乙酰氨基酚回归方程为y=0.651 1x+6.610 4,R2=0.994 5;茶碱回归方程为y=0.939 2x-5.575 1,R2=0.998,他们的线性范围是5~500μg/mL。该方法为茶碱、对乙酰氨基酚双组分体系研究提供依据,为其溶解度的测定提供方法支撑,作为高效液相色谱分离方法,分析快速,灵敏度高,重现性好。     

Biological Evaluation and X‐ray Co‐crystal Structures of Cyclohexylpyrrolidine Ligands for Trypanothione Reductase,an Enzyme from the Redox Metabolism of Trypanosoma

The tropical diseases human African trypanosomiasis, Chagas disease, and the various forms of leishmaniasis are caused by parasites of the family of trypanosomatids. These protozoa possess a unique redox metabolism based on trypanothione and trypanothione reductase (TR), making TR a promising drug target. We report the optimization of properties and potency of cyclohexylpyrrolidine inhibitors of TR by structure‐based design. The best inhibitors were freely soluble and showed competitive inhibition constants (K_i) against Trypanosoma (T.) brucei TR and T. cruzi TR and in vitro activities (half‐maximal inhibitory concentration, IC₅₀) against these parasites in the low micromolar range, with high selectivity against human glutathione reductase. X‐ray co‐crystal structures confirmed the binding of the ligands to the hydrophobic wall of the “mepacrine binding site” with the new, solubility‐providing vectors oriented toward the surface of the large active site.     

局部高温诱发CL-20/TNT共晶炸药内反应流传播的ReaxFF分子动力学模拟

为了更好地理解含能材料热点火以及热点成长现象和机理,采用基于第一性原理的Reax FF反应力场分子动力学方法模拟了CL-20/TNT共晶炸药内反应流传播的时空行为和初始化学反应过程。通过NVT系统和Berendsen温度耦合方法对含能材料两端连续快速加热并维持在高温条件激发反应流的产生和传播,并采用两种不同的热载荷(3000,4000 K)比较温度差异对初始热分解速率的影响。两端热载荷为4000 K时,热冲击传播过程中粒子瞬时平动速率可达0.5 km·s~(-1),高于3000 K时的情况。于此同时,两端高温将引发含能材料逐渐发生分解反应,同温度条件下,共晶中CL-20的分解速率高于TNT。另外,热载荷温度越高,共晶完全分解所需的时间越少。产物识别分析显示,CL-20/TNT共晶热分解的主要产物为NO_2,NO,H_2O,N_2,CO,CO_2,HONO,H_2O_2,CHON,H_2N,CH_2O,其中,NO_2是初始热分解产物,而最终产物为N_2,CO_2和H_2O。     

面向智能制造的工业结晶研究进展

工业结晶是一门“半艺术的科学”,具有多目标、非线性和强耦合的特点,在国际上被公认是最难设计的化工单元操作之一。面向智能制造发展的重大战略需求和历史机遇,基于国内外对工业结晶和智能制造的研究现状,拟构建基于智能制造的工业结晶多尺度研究框架。结合相关案例,总结了国内外人工智能、云计算、物联网等核心智能制造技术在工业结晶中的应用,重点分析讨论在溶解度预测、晶型预测、晶习预测、共晶预测与智能制造的发展现状和潜在结合点;总结了结晶过程中的感知、分析、决策的智能控制技术。     

典型食品物料的共晶、共熔温度研究

实验研究和分析结果表明一些典型食品物料的共晶温度比共熔温度低;共晶曲线比共熔曲线的斜率变化大;物料晶核形成阶段的电阻变化率小于物料大冰晶成长阶段的电阻变化率,进而又小于物料共晶阶段的电阻变化率。从理论上初步探讨了汤料的共晶、共熔温度与物料的物性、胶体结构及盐度有关。因此通过改变物料的胶体结构和盐度可降低被冻结物料的熔点,进而降低冻结能量的消耗。     

Potent Inhibitors of Plasmodial Serine Hydroxymethyltransferase (SHMT) Featuring a Spirocyclic Scaffold

With the discovery that serine hydroxymethyltransferase (SHMT) is a druggable target for antimalarials, the aim of this study was to design novel inhibitors of this key enzyme in the folate biosynthesis cycle. Herein, 19 novel spirocyclic ligands based on either 2‐indolinone or dihydroindene scaffolds and featuring a pyrazolopyran core are reported. Strong target affinities for Plasmodium falciparum (Pf) SHMT (14–76 nm ) and cellular potencies in the low nanomolar range (165–334 nm ) were measured together with interesting selectivity against human cytosolic SHMT1 (hSHMT1). Four co‐crystal structures with Plasmodium vivax (Pv) SHMT solved at 2.2–2.4 Å resolution revealed the key role of the vinylogous cyanamide for anchoring ligands within the active site. The spirocyclic motif in the molecules enforces the pyrazolopyran core to adopt a substantially more curved conformation than that of previous non‐spirocyclic analogues. Finally, solvation of the spirocyclic lactam ring of the receptor‐bound ligands is discussed.     

共结晶过程研究进展

简述了共结晶技术的发展现状、共结晶方式及共晶体产品的表征方法,展望了未来共结晶技术的发展前景,结果表明,共结晶技术应用广泛、发展前景远大。     

NTO·（3，5-DATr）含能离子盐和NTO/IMZ含能共晶的制备、晶体结构及性能

为改善钝感炸药3?硝基?1,2,4?三唑?5?酮(NTO)的酸性,将NTO分别与3,5?二氨基?1,2,4?三唑(3,5?DATr)、咪唑(IMZ)反应,制备得到了NTO·(3,5?DATr)含能离子盐(Ⅰ)和NTO/IMZ含能共晶(Ⅱ)。通过溶剂挥发法培养得到了单晶,利用X?射线单晶衍射仪确定了其晶体结构。晶体Ⅰ属于单斜晶系,空间群为P21/c,Mr=229.19,晶胞参数a=3.5687(7)?,b=17.245(3)?,c=14.655(3)?,β=93.79(3),V=899.9(3)?³,Z=4,D_c=1.692 g·cm^-3;晶体Ⅱ属于正交晶系,空间群为Pbcn,Mr=207.17,晶胞参数a=16.9398(16)?,b=5.6802(5)?,c=17.9111(19)?,V=1723.4(3)?³,Z=4,D_c=1.597 g·cm^-3。采用差示扫描量热法(DSC)和热失重法(TG)研究了其热分解行为,结果表明二者均具有良好的热稳定性。运用Gaussian 09程序对化合物结构进行优化并计算其生成焓,用EXPLO 5软件对二者的爆速和爆压进行了评估(Ⅰ:D=7662.3 m·s^-1,p=21.0 GPa;Ⅱ:D=6490.2 m·s^-1,p=14.6 GPa)。采用BAM方法测试了其机械感度,结果表明,二者均对撞击和摩擦钝感(IS>40 J,FS>360 N)。利用pH计测试了化合物标样的pH值,在0.01 mol·L^-1的标准溶液中NTO,Ⅰ和Ⅱ的pH值分别为2.92(22.8℃),4.10(22.7℃),4.98(22.8℃),表明盐和共晶的形成在一定程度上改善了NTO的酸性。     

In Vitro Release and Diffusion Studies of Promethazine Hydrochloride from Polymeric Dermatological Bases Using Cellulose Membrane and Hairless Mouse Skin

The study was designed to investigate the feasibility of developing a transdermal drug dosage form of promethazine hydrochloride (PMH). The in vitro release and diffusion characteristics of PMH from various dermatological polymeric bases were studied using cellulose membrane and hairless mouse skin as the diffusion barriers. These included polyethylene glycol (PEG), hydroxypropyl methylcellulose (HPMC), cross-linked microcrystalline cellulose, and carboxyl methyl cellulose sodium (Avicel® CL-611), and a modified hydrophilic ointment USP. In addition, the effects of several additive ingredients known to enhance the drug release from topical formulations were evaluated. The general rank order for the drug release from these formulations using cellulose membrane was observed to be PEG > HMPC > Avicel CL-611 > hydrophilic ointment base. The inclusion of the additives had little or no effect on the drug diffusion from these bases, except for the hydrophilic ointment formulation containing 15% ethanol, which provided a significant increase in the drug release. However, when these formulations were studied for drug diffusion through the hairless mouse skin, the Avicel CL-611 base containing 15% ethanol exhibited the optimum drug release. The data also revealed that this formulation gave the highest steady-state flux, diffusion, and permeability coefficient values and correlated well with the amount of drug release.