可生物降解的药物缓释膜片研究进展

利用生物降解高分子材料物理包埋或化学结合需要缓释的药物制成植入膜片,药物从聚合物的孔道中扩散出来,以一定的速率释放,从而达到局部缓释、控释的目的。本文从聚合物材料、制备方法和释放机理等方面综述了近年来国内外生物降解药物缓释膜片的进展情况。     

高分子前药研究进展

高分子前药可以控制药物释放速度,降低小分子药物的毒副作用,减少抗药性,增强抗肿瘤药物的靶向性和选择性,提高多肽、蛋白质和核酸类药物的稳定性和有效利用率,引起国内外广泛关注.本文综述了近年来高分子药物的研究进展,主要从高分子载体材料的选择与改性对载药量、生物相容性和肾排泄的影响,以及化学合成过程中载体和药物末端的修饰、空...     

移动学习App在药物化学教学中的应用

立足探索移动学习模式,结合药物化学的学科特点以及研究生学习实际情况,从药物化学信息、实验应用、药物设计等方面介绍相关移动学习App。结合案例比较移动学习及PC端的优劣。     

高分子药物及载体材料

高分子药物由于具有良好的生物降解性和生物相容性,可以控制药物释放速度,能够降低药物的毒副作用,减少抗药性,提高药物的稳定性和有效利用率,从而引起国内外广泛关注.本文从自身具有药理活性的高分子、高分子载体药物两个方面综述了近年来高分子药物及载体材料的研究进展.按化学结合力不同将高分子载体药物分为高分子前药和高分子络合物药...     

药物化学全英教学中的思考和创新实践

药物化学全英教学对培养国际化创新药学人才起到重要的支撑作用。本文结合药物化学全英教学工作实践中发现的痛点问题——教学内容局限和抽象化、师资队伍本土化等方面的不足,秉承“以生为本、接轨国际”的教学理念,从教学师资、教学内容和教学方式改革等角度对药物化学全英教学进行创新实践研究。提出药物化学全英教学应以国际化教学为中心的前提下,从教学团队建设、教学方法、教学课程体系和教材四个方面建设创新课程教学体系,提高教学质量。     

基因组学对基于结构的药物设计的影响*

基于靶标结构的药物设计方法是先导药物设计的重要手段.近年来,随着基因组计划的顺利进行,基因组学对药物设计有着巨大的冲击和影响.本文试图从近几年的一些研究领域如结构基因组学、化学基因组学、微生物基因组学等来综述基因组学对基于药物作用靶标的分子设计方法的影响.     

基于多肽的药物递送系统研究进展

药物递送系统是将药物输送到药物作用靶点的系统,理想的递送系统可以提高药物作用效果并降低给药剂量和毒副作用.本文综述了药物递送系统中的多肽类药物递送系统的研究进展.多肽具有易合成、易代谢、免疫原性低、毒副作用低等优点,多肽支链上大量的官能团可以和药物偶联,是药物递送系统的重要发展方向.本文从靶向肽、穿透肽、响应肽和组装肽四个方面介绍了多肽药物递送系统的原理和实例.组装肽可以形成纳米结构,显著提升多肽药物递送系统的稳定性,可以实现长效释放.组装肽体内原位调控进一步增加了多肽药物递送系统的智能型、精准性,展现出巨大的转化潜力.     

生物医用高分子在癌症药物治疗中的应用

利用生物医用高分子作载体,化学结合或物理包裹抗肿瘤化学药物、生物工程药物和放射药物,制剂通过植入或靶向运输至肿瘤区域。可增强药物在运输及吸收过程中的稳定性,提高药物的生物利用度,药物以一定速率从制剂中缓慢释放,可简化服用程序,在肿瘤区域维持较高的药物浓度,同时降低药物对全身的毒副作用。本文综述了生物医用高分子在高分子导向药物、抗肿瘤药物聚合物微球制剂,植入制剂以及肿瘤栓塞治疗中的应用。     

医用化学与药物化学课程中神奇的甲基化效应

在促进基础学科与应用学科交叉融合以加快“高等学校双一流”建设的时代背景下,以“神奇的甲基化效应”为例阐述医用化学与药物化学课程内容的融合,从化学结构的角度综合分析了甲基的引入对药物代谢动力学性质、分子构象或脂溶性的改变,从而减轻药物的毒性、增强药物活性、改善成药性等。将综合性、应用性强的药物化学与理论性强的医用化学进行融合,使学生既掌握化学的经典原理,又能从新药设计的实际情况出发,构建对学生职业成长有意义的知识体系,以期克服传统教学模式下理论知识与实际应用脱节的缺点,促进教学质量的提高。     

分子对接在药物虚拟筛选中的应用进展

虚拟筛选是药物设计的重要手段之一,利用小分子化合物与药物靶标间的分子对接运算,研究人员可以准确地获取两者之间的相互作用情况,从候选化合物库中快速筛选出潜在的药物或药物前体,从而加速药物开发过程。介绍了虚拟筛选与分子对接的相关原理与流程,主要综述了对药物进行虚拟筛选时所涉及的分子对接技术类型、常见的分子对接软件以及分子对接典型样例。分子对接对提高虚拟筛选的效率、降低药物开发的成本具有重要的现实意义。     

Drugs That Changed Society: History and Current Status of the Early Antibiotics: Salvarsan,Sulfonamides, and β-Lactams

The appearance of antibiotic drugs revolutionized the possibilities for treatment of diseases with high mortality such as pneumonia, sepsis, plaque, diphtheria, tetanus, typhoid fever, and tuberculosis. Today fewer than 1% of mortalities in high income countries are caused by diseases caused by bacteria. However, it should be recalled that the antibiotics were introduced in parallel with sanitation including sewerage, piped drinking water, high standard of living and improved understanding of the connection between food and health. Development of salvarsan, sulfonamides, and β-lactams into efficient drugs is described. The effects on life expectancy and life quality of these new drugs are indicated.     

毛细管电泳法手性拆分4种氨酸和2种手性药物对映体

以双(6-氧-β-羧甲基-1,4-丁烯二酸单酯)-β-环糊精(DOCB-β-CD）作为手性添加剂,利用毛细管电泳对氨基酸和手性药物对映体进行拆分研究。 以20 mmol/L磷酸盐为缓冲溶液,考察了手性添加剂的浓度及缓冲溶液的pH值与分离电压等对拆分效果的影响,并在其优化条件下,实现了4种DL-氨基酸（苯丙氨酸、色氨酸、酪氨酸和组氨酸）以及手性药物（罗格列酮和酮洛芬）对映体的基线分离。     

Quantitative and Qualitative Analysis of the Anti-Proliferative Potential of the Pyrazole Scaffold in the Design of Anticancer Agents

The current work presents an objective overview of the impact of one important heterocyclic structure, the pyrazole ring, in the development of anti-proliferative drugs. A set of 1551 pyrazole derivatives were extracted from the National Cancer Institute (NCI) database, together with their growth inhibition effects (GI%) on the NCI’s panel of 60 cancer cell lines. The structures of these derivatives were analyzed based on the compounds’ averages of GI% values across NCI-60 cell lines and the averages of the values for the outlier cells. The distribution and the architecture of the Bemis–Murcko skeletons were analyzed, highlighting the impact of certain scaffold structures on the anti-proliferative effect’s potency and selectivity. The drug-likeness, chemical reactivity and promiscuity risks of the compounds were predicted using AMDETlab. The pyrazole ring proved to be a versatile scaffold for the design of anticancer drugs if properly substituted and if connected with other cyclic structures. The 1,3-diphenyl-pyrazole emerged as a useful scaffold for potent and targeted anticancer candidates.     

含环丙基结构的药物研究进展

环丙基的化学结构不同于直链脂肪烃和其他多元脂肪环,在药物分子的设计中经常被使用,具有增强药物的药效、增强代谢稳定性、降低脱靶作用、增强对受体的亲和力、限制多肽的水解作用、增加血脑屏障渗透率、降低血浆清除率以及改善药物的解离度(pK_a)等功效。含有环丙基结构的药物被开发用于治疗呼吸系统疾病、精神障碍类疾病、内分泌和代谢系统疾病、感染性疾病、神经系统疾病、心脑血管疾病以及肿瘤等。本文将对含有环丙基结构药物的研究进展进行综述。     

Magnetic microspheres for targeting of drugs

Magnetic microspheres were prepared from starch. The microspheres could be crosslinked with various agents, and drugs could be entrapped adsorbed, or covalently coupled to the microspheres.     

Nano Carrier Drug Delivery Systems for the Treatment of Neuropsychiatric Disorders: Advantages and Limitations

Neuropsychiatric diseases are one of the main causes of disability, affecting millions of people. Various drugs are used for its treatment, although no effective therapy has been found yet. The blood brain barrier (BBB) significantly complicates drugs delivery to the target cells in the brain tissues. One of the problem-solving methods is the usage of nanocontainer systems. In this review we summarized the data about nanoparticles drug delivery systems and their application for the treatment of neuropsychiatric disorders. Firstly, we described and characterized types of nanocarriers: inorganic nanoparticles, polymeric and lipid nanocarriers, their advantages and disadvantages. We discussed ways to interact with nerve tissue and methods of BBB penetration. We provided a summary of nanotechnology-based pharmacotherapy of schizophrenia, bipolar disorder, depression, anxiety disorder and Alzheimer’s disease, where development of nanocontainer drugs derives the most active. We described various experimental drugs for the treatment of Alzheimer’s disease that include vector nanocontainers targeted on β-amyloid or tau-protein. Integrally, nanoparticles can substantially improve the drug delivery as its implication can increase BBB permeability, the pharmacodynamics and bioavailability of applied drugs. Thus, nanotechnology is anticipated to overcome the limitations of existing pharmacotherapy of psychiatric disorders and to effectively combine various treatment modalities in that direction.     

Review of the applications of different analytical techniques for coxibs research

An extensive survey of the literature published in analytical and pharmaceutical chemistry journals has been conducted and analytical methods which were developed and used for the determination of some of the COX-2 inhibitors, a subclass of non-steroidal anti-inflammatory drugs (NSAIDs) in bulk drugs, formulations, and biological fluids have been reviewed. This review covers the time period from 1999 to present, during which over 140 analytical procedures including chromatographic, spectrometric, electrophoretic and voltammetric techniques were reported. Presented applications concern analysis of coxibs from pharmaceutical formulations and biological samples.     

合成化合物动物体内抗肿瘤实验方法研究进展

进行了动物体内抗肿瘤活性研究的多为天然药物,但其来源有限;虽然用于抗肿瘤研究的合成化合物种类较多,但对于其在动物体内抗肿瘤研究又相对偏少,所以,合成化合物抗肿瘤体内研究已经成为研究热点之一。本文对合成化合物抗肿瘤作用机制、体内肿瘤模型建立方法和体内抑瘤实验研究等方面的研究进展进行了评述,并通过大量实验数据对合成化合物毒性评价方法、抑瘤基本观察指标测定、氧化损伤相关酶活力的测定方法、组织病理学评价方法等体内抑瘤实验的评价标准和方法进行了详细总结,提出了合成化合物在体内动物抗肿瘤实验研究方法中亟待解决的问题,为新型抗肿瘤合成化合物体内药学活性研究提供有益的参考。     

Identification of Potential Parkinson’s Disease Drugs Based on Multi-Source Data Fusion and Convolutional Neural Network

Parkinson’s disease (PD) is a serious neurodegenerative disease. Most of the current treatment can only alleviate symptoms, but not stop the progress of the disease. Therefore, it is crucial to find medicines to completely cure PD. Finding new indications of existing drugs through drug repositioning can not only reduce risk and cost, but also improve research and development efficiently. A drug repurposing method was proposed to identify potential Parkinson’s disease-related drugs based on multi-source data integration and convolutional neural network. Multi-source data were used to construct similarity networks, and topology information were utilized to characterize drugs and PD-associated proteins. Then, diffusion component analysis method was employed to reduce the feature dimension. Finally, a convolutional neural network model was constructed to identify potential associations between existing drugs and LProts (PD-associated proteins). Based on 10-fold cross-validation, the developed method achieved an accuracy of 91.57%, specificity of 87.24%, sensitivity of 95.27%, Matthews correlation coefficient of 0.8304, area under the receiver operating characteristic curve of 0.9731 and area under the precision–recall curve of 0.9727, respectively. Compared with the state-of-the-art approaches, the current method demonstrates superiority in some aspects, such as sensitivity, accuracy, robustness, etc. In addition, some of the predicted potential PD therapeutics through molecular docking further proved that they can exert their efficacy by acting on the known targets of PD, and may be potential PD therapeutic drugs for further experimental research. It is anticipated that the current method may be considered as a powerful tool for drug repurposing and pathological mechanism studies.     

Preparation of Antihypertensive Drugs in Biological Matrix with Solvent Front Position Extraction for LC–MS/MS Analysis

Solvent front position extraction procedure was used to prepare biological samples containing selected antihypertensive drugs (ramipril, lercanidipine, indapamide, valsartan, hydrochlorothiazide, perindopril, and nebivolol). Substances separated from the biological matrix components (bovine serum albumin) were quantified by means of liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Sample preparation process was performed with the use of a prototype horizontal chamber with a moving pipette driven by a 3D printer mechanism enabling a controlled eluent flow velocity. Application of this device was advantageous for simultaneous preparation of several samples for further quantitative analysis, with a synchronized reduction of manual operations and solvent consumption. Quantitative results obtained for the majority of the investigated antihypertensive drugs in a complex biological matrix were satisfactory. The values of the %RSD were around 5% for six of the seven substances (with the exception of indapamide). The method exhibits a suitable accuracy (the relative error percentage was below 10% for most drugs). The values of LOD and LOQ were in the range of 1.19 µg/L–8.53 µg/L and 3.61 µg/L–25.8 µg/L, respectively.