微粉（和微晶）纤维素的微细结构

探讨了微粉化过程对各种纤维素材料超分子结构的影响，结果表明，稀盐酸水解制得的微粉（和微晶）纤维素，在结晶状态（如聚合度，结晶度，晶粒尺寸等）及晶粒聚集体的形态结构上，均随纤维素晶型的不同而变，并与硫酸水解和机微粉化不同，Ｘ－射线衍射分析显示，微粉化产物仍保持其纤维素材料原来的晶型和两相（晶区与非晶区）共存的微细结构。     

太赫兹技术在药物化学研究领域中的应用*

太赫兹(THz)技术及其应用研究近些年发展迅速,许多研究表明该技术在国防安全、信息通信、材料、环境、化学和生物医学等领域有巨大的应用前景。本文就近年来利用太赫兹光谱和太赫兹成像技术在药物化学领域中的应用研究进行综述。介绍了太赫兹时域光谱技术（THz-TDS）在药物活性成分（Active Pharmaceutical Ingredients, APIs）的检测、异构体的区分、药物的多晶型和假多晶型的鉴别以及混合物的定性与定量分析等方面取得的研究成果和进展;阐述了太赫兹成像技术在分析药物的物理化学性质和包衣膜厚度、密度、结构特性,以及监测产品的一致性和完整性方面的应用优势。此外,还介绍了太赫兹技术在药物动力学研究及药物生产过程分析中的创新性应用研究。     

过程监测与控制中的流动注射方法

本文综述了过程监测与控制中的流动注射方法,内容包括仪器装置、技术及其在工业生产、环境污染、药物溶出和生物过程分析中的应用。     

锂离子电池硅纳米线负极材料研究

采用涂膜法和直接生长成膜法分别制备两种硅纳米线电极.XRD、SEM和充放电曲线表征、观察和测定材料嵌锂状态过程的结构、形貌及电化学性能.与涂膜法相比,直接生长成膜法制备的硅纳米线电极具有较高的比容量、良好的循环寿命及较好的倍率性能;直接生长成膜法制备的硅纳米线电极,其嵌锂过程硅由晶态逐渐转变为非晶态,且其纳米线直径逐渐增大,但线状结构仍保持完好,进而防止了电极粉化和脱落.     

TiO2表面包覆SiO2和Al2O3的机理和结构分析

在二氧化钛的表面上包覆一层保护膜,使二氧化钛的表面和周围介质之间产生屏障,从而降低二氧化钛的光化学活性,有利于提高二氧化钛的分散性、耐光性、耐候性和抗粉化性.     

毛细管电泳药物筛选方法与技术

毛细管电泳（CE）在新药研发领域显示着重要的应用前景。CE使用水溶液介质作为实验体系,保证了药物筛选在类似于生命介质的环境中进行,优于其他传统体外仪器筛选方法。除了维持被筛选分子和作用对象的生物活性外,CE筛选过程着重突出配体与受体之间的相互作用。毛细管电泳药物筛选瞄准与药理学理论相关的重要参数,如结合常数K_b 、结合速率常数K_on 和解离速率常数K_off ,有利于模拟并预测机体内靶标与药物之间的相互作用过程。该文回顾了毛细管电泳进行药物筛选的历史,评述了毛细管电泳药物筛选方法所依据的理论和相对成熟的各种常用方法,并抽取了部分典型实例以及相关技术进行说明,对以亲和毛细管电泳、动力学毛细管电泳为手段的药物筛选方法进行了介绍,包括分子和细胞层次的药物筛选,以及针对不同类型的候选药物的研究工作都有提及。毛细管电泳与多种技术的联用,包括与质谱以及化学发光等联用发挥了更大的效能。联用方法还应用于中药有效成分的筛选。毛细管电泳在DNA编码化合物库筛选中将有良好应用前景。馏分收集的发展为筛选药物提供了广阔前景,它配合指数富集配体系统进化技术为毛细管电泳药物筛选提供了更多可能。总之,毛细管电泳多样可选的药物筛选方法和技术将为新概念的药物筛选与药物评价提供有力支撑。     

预处理条件对Ni-Ce-P非晶态合金液相加氢活性的影响

采用真空骤冷技术制备了Ni82Ce0.31P17.7和Ni82P18非晶态合金。通过高压氢气中热处理, 使其粉化。DSC研究结果表明加入少量Ce使Ni-P非晶态合金晶化温度提高160℃。用高压反应釜考察了氧化温度和氢还原温度对Ni-De-P非晶态合金本乙烯液相加氢活性的影响, 并对比了Ni-P和Ni-Ce-P的加氢活性, 活性测试的结果表明: 氧化、还原处理过程使Ni-Ce-P加氢活性显著增加, 最佳的预处理条件是240℃氧化1h, 300℃氢气还原2h; Ni-Ce-P加氢活性是Ni-P加氢活性的3-4倍, 用AES和XPS研究了氧化、还原过程中,Ni-Ce-P表面性质的变化。     

“是金子总会发光”——金及其化合物在新冠病毒检测及治疗中的应用

胶体金、金配合物在新型冠状病毒的检测与药物研发中发挥着重要的作用。本文采用生动的语言、拟人化的方式，从金元素的角度讲述了免疫胶体金技术检测新冠的原理和金配合物作为抗新冠药物的发现过程。     

生物制药领域蛋白质团聚检测技术的研究进展

21世纪是生物制药的黄金时代,以重组蛋白药物和治疗性抗体为代表的蛋白质药物已成为生物技术药物的重要组成部分,其对恶性肿瘤、自身免疫性疾病、病毒感染等重大疾病的治疗效果和生物安全性远高于小分子化学药物。但是蛋白质稳定性差,在生产、纯化、运输和储存等过程中,容易因环境刺激或自身稳定性等因素产生团聚,从而导致药效降低,并可能引发免疫反应。发展灵敏度高、分辨率好、简便实用的蛋白质团聚检测技术和方法,对蛋白质药物的研发和改良可起到积极的推动作用。本文针对蛋白质团聚的检测技术和方法进行综述,从检测原理、性能和应用范围等方面,对体积排阻色谱法、凝胶电泳法、分析超速离心法、场流分离法、浊度法、动态光散射法、纳米颗粒跟踪分析技术、流式细胞术和电子显微技术等进行分析比较,并对蛋白质团聚检测技术未来的发展趋势进行了展望。     

抗癌药物阿克拉霉素-A的氧化还原代谢机理研究

大多数化疗药物因很强的毒副作用在临床应用中受到很大的限制,阿克拉霉素为蒽环药物家族新成员,因其抗癌活性高和毒副作用低在抗肿瘤药物中占有重要地位．本论文将药物置于代谢模型内,以光谱技术现场监测药物的代谢过程,研究了阿克拉霉素-A的氧化还原代谢机理．阿克拉霉素．A在体内的代谢过程为先通过一步二电子过程还原生成阿克拉氢醌．A,再脱去糖．其脱糖反应与介质的pH密切相关．脱糖、异构化后的产物7-去氧阿克拉霉醌经缔合后可生成双分子缔合物．整个代谢过程中并不产生半醌自由基,因而对心脏和细胞的毒性较小．研究结果同时也表明药物分子中的糖环结构与药物代谢及药物的毒副作用密切相关．研究成果有助于深入探讨药物的构效关系,对药物的临床应用有着重要的实际意义．     

Molecular Simulation and Statistical Learning Methods toward Predicting Drug–Polymer Amorphous Solid Dispersion Miscibility,Stability, and Formulation Design

Amorphous solid dispersions (ASDs) have emerged as widespread formulations for drug delivery of poorly soluble active pharmaceutical ingredients (APIs). Predicting the API solubility with various carriers in the API–carrier mixture and the principal API–carrier non-bonding interactions are critical factors for rational drug development and formulation decisions. Experimental determination of these interactions, solubility, and dissolution mechanisms is time-consuming, costly, and reliant on trial and error. To that end, molecular modeling has been applied to simulate ASD properties and mechanisms. Quantum mechanical methods elucidate the strength of API–carrier non-bonding interactions, while molecular dynamics simulations model and predict ASD physical stability, solubility, and dissolution mechanisms. Statistical learning models have been recently applied to the prediction of a variety of drug formulation properties and show immense potential for continued application in the understanding and prediction of ASD solubility. Continued theoretical progress and computational applications will accelerate lead compound development before clinical trials. This article reviews in silico research for the rational formulation design of low-solubility drugs. Pertinent theoretical groundwork is presented, modeling applications and limitations are discussed, and the prospective clinical benefits of accelerated ASD formulation are envisioned.     

Analysis of molecular interactions in solid dosage forms; challenge to molecular pharmaceutics

The molecular states of active pharmaceutical ingredients (APIs) in pharmaceutical dosage forms strongly affect the properties and quality of a drug. Various important fundamental physicochemical studies were reviewed from the standpoint of molecular pharmaceutics. Mechanochemical effects were evaluated in mixtures of APIs and pharmaceutical additives. Amorphization, complex formation and nanoparticle formation are observed after grinding process depending on the combination of APIs and pharmaceutical additives. Sealed-heating method and mesoporous materials have been used to investigate drug molecular interactions in dosage forms. Molecular states have been investigated using powder X-ray diffraction, thermal analysis, IR, solid state fluorometry, and NMR.     

大环化合物作为药物增溶剂的应用

药物研发的过程中,越来越多的化合物存在溶解性低的问题,因此提高药物溶解度是目前迫切需要解决的问题。环糊精、杯芳烃、葫芦脲等大环化合物可以通过主客体作用形成包合物从而增加难溶性药物的水溶性。本文介绍了几种大环化合物在药物增溶领域的应用。首先,基于大环化合物化学结构和空腔属性的差异,列举了它们可增溶药物的种类和范围;其次,主客体的动态可逆包合作用还能改善药物稳定性、溶出速率等,从而使药物的生物利用度进一步提升;另外,补充了大环化合物的相关毒理学数据,这增加了其作为药物辅料批准上市的可能性;最后,总结了大环化合物作为增溶剂存在的问题,并指出空腔尺寸的局限和更全面的安全性评估是未来研究的方向。     

Solubility Enhancement of Antidiabetic Drugs Using a Co-Crystallization Approach

The co-crystallization approach has been used to enhance specific desirable properties of active pharmaceutical ingredients (APIs) such as solubility, dissolution rate, and stability. Solubility is a fundamental property that affects the bioavailability and dosage of the API. The co-crystal approach is one of the emerging methods with the potential for improving the solubility of these drugs. This paper reviews the latest progress on improving the solubility of some antidiabetic drug molecules using the co-crystal approach.     

Development and validation of a stability-indicating reversed-phase high performance liquid chromatography method for assay of betamethylepoxide and estimation of its related compounds

Betamethylepoxide (16beta-methyl-Delta(1,4)-pregnadiene-9beta-11beta-oxide-17alpha,21-diol-3,20-dione) is a key intermediate for the synthesis of various active pharmaceutical ingredients (APIs) of steroid compounds. A stability-indicating reversed-phase HPLC method for assay of betamethylepoxide and estimation of its related compounds has been developed and validated. This method can accurately quantitate betamethylepoxide in the presence of numerous structurally related compounds (including the alpha-epimer, known as alphamethylepoxide). This method can also adequately separate most of the impurities from each other and estimate their quantities in betamethylepoxide samples. The stability-indicating capability of this method has been demonstrated by adequate separation of the degradation products from betamethylepoxide in stress degraded and aged stability samples. The HPLC column used in the method was a 5 cm YMC Hydrosphere C(18) column (4.6 mm I.D.) and the mobile phase consisted of (A) water and (B) acetonitrile:methanol (8:25, v/v).     

Evaluation of Multiplexed CE with UV Detection for Rapid pK a Estimation of Active Pharmaceutical Ingredients

The acid dissociation constant (pK _a) is a key physicochemical parameter for characterizing active pharmaceutical ingredients (APIs). Early determination of pK _a values is highly desirable in drug discovery, pharmaceutical process research and formulation design. To overcome the challenges of limited sample availability and potential low purity of API samples at early stages of drug development, as well as to increase sample analysis throughput, a multiplexed 96-channel capillary electrophoresis with UV detection was evaluated as a practical approach for high throughput pK _a estimation of proprietary APIs in support of pharmaceutical research. Proprietary APIs with diverse structures were examined using the approach. The pK _a values were successfully determined with good accuracy and precision. System robustness was demonstrated and analysis of at least eight samples can be completed within 1 h. A rapid pK _a estimation procedure for marginally soluble APIs was proposed by performing single-point multiplexed CE–UV measurement without extrapolation using 10 or 20% methanol as co-solvent. Direct pK _a estimation of APIs using DMSO solution samples and crude reaction samples containing a large amount of solvents and reagents and high level of impurities was also demonstrated using the multiplexed CE–UV approach.     

A tale of two polymorphic pharmaceuticals: pyrithyldione and propyphenazone and their 1937 co-crystal patent

A co-crystal of two polymorphic active pharmaceutical ingredients (APIs), first reported and patented in 1937, has been prepared and thoroughly characterised, including crystal structure analysis. The existence of four crystal forms of one of the APIs, the sedative and hypnotic active pharmaceutical ingredient 3,3-diethyl-2,4(1H,3H)-pyridinedione, pyrithyldione (PYR), and of three crystal forms of the co-crystal-forming second API, the non-steroidal anti-inflammatory drug 1,2-dihydro-1,5-dimethyl-4-(1-methylethyl)-2-phenyl-3H-pyrazol-3-one, propyphenazone (PROP), has been reported previously, but they have only been partly characterised. For both compounds, none of the metastable forms exist at room temperature. DSC, hot-stage microscopy, X-ray diffraction and powder synchrotron X-ray diffraction were employed to characterise the polymorphic forms and to determine the crystal structures of forms I-III of PYR and forms I and II of PROP.     

Polymorphism of progesterone

Solid dispersions are used in pharmaceutical technology in order to improve solubility and/or dissolution kinetics of poorly water soluble drugs [1, 2, 3]. A preliminary study concerning progesterone structure after melting revealed the existence of a drug polymorphism after cooling, and gave the opportunity to specify the manufacturing conditions in order to obtain the stable form of this hormone [4]. In this work, two different types of progesterone solid dispersion have been compared. The first one is obtained by a slow cooling rate of the drug in the presence of polyoxyethylene glycol 6000 and the second one after quenching in the presence of saccharose distearate. DSC and radiocrystallographic studies of the solid dispersions served to specify the nature of the compounds obtained and to characterize the physical structure of the hormone in the solidified melts.     

Study on the Supramolecular Inclusion Complex of β-Cyclodextrin with Retinoic Acid

The importance of Vitamin A for human health has been stressed in resent studies, meanwhile its derivative so-called retinoic acid (RA) has been widely used as pharmaceutical to treat several types of skin disease and cancer. However the application of retinioc acid is restrained for its poor water solubility, unstability and side affect on the human body. A large number of studies in pharmaceutical field showed that β-CD could inqjrove the water solubility of poorly soluble of drugs, reduce the toxicity and increase the dissolution rate, In the present work, the inclusion compound of retinoic acid with β-cyclodextrin was prepared by coprecipitating method, the structure of resulting product was studied by elemental analysis, differental scanning caloriemetry(DSC) analysis, FT-IR spectroscopy and X-ray diffractometry, and the formed supramolecule self-assembles in aqueous solution according to molar ratio 2:1 of host-guest.     

Subcritical Water Extraction of Salvia miltiorrhiza

In this work, a green extraction technique, subcritical water extraction (SBWE), was employed to extract active pharmaceutical ingredients (APIs) from an important Chinese medicinal herb, Salvia miltiorrhiza (danshen), at various temperatures. The APIs included tanshinone I, tanshinone IIA, protocatechualdehyde, caffeic acid, and ferulic acid. Traditional herbal decoction (THD) of Salvia miltiorrhiza was also carried out for comparison purposes. Reproduction assay of herbal extracts obtained by both SBWE and THD were then conducted on Caenorhabditis elegans so that SBWE conditions could be optimized for the purpose of developing efficacious herbal medicine from Salvia miltiorrhiza. The extraction efficiency was mostly enhanced with increasing extraction temperature. The quantity of tanshinone I in the herbal extract obtained by SBWE at 150 °C was 370-fold higher than that achieved by THD extraction. Reproduction evaluation revealed that the worm reproduction rate decreased and the reproduction inhibition rate increased with elevated SBWE temperatures. Most importantly, the reproduction inhibition rate of the SBWE herbal extracts obtained at all four temperatures investigated was higher than that of traditional herbal decoction extracts. The results of this work show that there are several benefits of subcritical water extraction of medicinal herbs over other existing herbal medicine preparation techniques. Compared to THD, the thousand-year-old and yet still popular herbal preparation method used in herbal medicine, subcritical water extraction is conducted in a closed system where no loss of volatile active pharmaceutical ingredients occurs, although analyte degradation may happen at higher temperatures. Temperature optimization in SBWE makes it possible to be more efficient in extracting APIs from medicinal herbs than the THD method. Compared to other industrial processes of producing herbal medicine, subcritical water extraction eliminates toxic organic solvents. Thus, subcritical water extraction is not only environmentally friendly but also produces safer herbal medicine for patients.