药品物流多中心选址优化研究

为降低药品物流配送成本、提高药品配送效率。本文针对国家带量集中采购药品配送问题,构建了药品物流多中心选址-路径优化双目标模型。并结合模糊C-均值聚类算法(FCMA)、模拟退火算法和禁忌搜索算法各自优点,设计出了FCM-TS-SA混合算法,最后通过真实案例进行了验证、对比和分析。     

基于前景理论的药品质量安全监管演化博弈分析

现有药品质量安全监管的相关研究多从理性假设出发探讨政府与企业的互动机理,鲜有考虑企业质量安全意识的有限理性,导致模型对现实的解释能力不足。运用前景理论,通过价值函数和权重函数构建演化博弈的收益前景矩阵,研究了政府和药品生产企业的博弈过程,得到了影响企业质量安全意识的约束条件及因素。同时,研究了上市许可持有人质量激励、惩罚机制对药品生产企业质量安全意识的影响。研究结果表明:过度自信、风险偏好等是影响企业质量安全意识的重要因素;上市许可持有人的质量激励与惩罚能否发挥作用取决于企业的风险态度;在质量激励、惩罚条件下,上市许可持有人需加大监督或惩罚力度来改善企业的质量安全意识。     

A genetic algorithm for the automated generation of molecules within constraints

Summary A genetic algorithm has been designed which generates molecular structures within constraints. The constraints may be any useful function, for example an enzyme active site, a pharmacophore or molecular properties from pattern recognition or rule-induction analyses. The starting point may be random or may utilise known molecules. These are modified to grow into families of structures which, using the evolutionary operators of selection, crossover and mutation evolve to better fit the constraints. The basis of the algorithm is described together with some applications in lead generation, 3D database construction and drug design. Genetic algorithms of this type may have wider applications in chemistry, for example in the design and optimisation of new polymers, materials (e.g. superconducting materials) or synthetic enzymes.     

Direct analysis of thin-layer chromatographic spots of narcotics by means of diffuse reflectance Fourier transform infrared spectroscopy

The technique of diffuse reflectance Fourier transform infrared spectrometry (DRIFT) as an in situ detection method was used for the qualitative and quantitative analysis of drugs (heroin, cocaine and codeine) separated by thin layer chromatography.It was found that at a given interferometer throughput and detector sensitivity the quality of the spectrum depends strongly in the type of the chromatographic thin layer used. A detection limit of approx. 2 g was attained on a microcrystalline cellulose thin layer with a dynamically aligned Bio-Rad Digilab FTS 60A/896 type interferometer and room temperature DTGS detector. A reliable qualitative analysis can be made with as little as 10 to 15 g drug per spot.     

A rapid and simple method for the isolation of mutant variants regulating tissue-specific expression of the tni gene through drug selection

TnINEO fusion gene was constructed by fusing 3.4-kbp of quailTnI genomic DNA sequences spanning the promoter to exon 5 and aneo gene in frame. A myoblast cell line was established after transfection of pTnINEO. Since this cell line was passaged several times, a high frequency of neomycin (G418) sensitivity conversion was detected. Two drug-resistant variants were analyzed through genomic Southern blot and S1 nuclease protection assay. One variant has a mutation(s) in the regulatory element that activated the dormantTnI promoter-enhancer in myoblast, and the other has shown the genomic rearrangement. This result presented the possibility of isolating factor(s) that activate the muscle-specificTnI promoter simply by screening drug-resistant cells having appropriate mutations.     

Structure-based identification and clustering of protein families and superfamilies

Summary We describe an approach to protein structure comparison designed to detect distantly related proteins of similar fold, where the procedure must be sufficiently flexible to take into account the elasticity of protein folds without losing specificity. Protein structures are represented as a series of secondary structure elements, where for each element a local environment describes its relations with the elements that surround it. Secondary structures are then aligned by comparing their features and local environments. The procedure is illustrated with searches of a database of 468 protein structures in order to identify proteins of similar topology to porcine pepsin, porphobilinogen deaminase and serum amyloid P-component. In all cases the searches correctly identify protein structures of similar fold as the search proteins. Multiple cross-comparisons of protein structures allow the clustering of proteins of similar fold. This is exemplified with a clustering of /- and -class protein structures. We discuss applications of the comparison and clustering of three-dimensional protein structures to comparative modelling and structure-based protein design.     

新疆产12种中草药中微量金属元素的测定

本文测定了新疆产新疆党参,新疆元胡等１２种中草药中十种微量金属元素的含量．结果表明这些中草药中具有显著生理活性的Ｚｎ、Ｆｅ、Ｃｕ、Ｍｎ等元素．它们的含量除了个别样品外均大于或接近于国内其它地区所产的同种中草药、根据冠心病病因的Ｚｎ／Ｃｕ值假说和微量金属元素的含量关系,新疆产１２种中草药也可用于防治冠心病．     

Evaluation of the limit of performance of an analytical method based on a statistical calculation of its critical concentrations according to ISO standard 11843: Application to routine control of banned veterinary drug residues in food according to European Decision 657/2002/EC

Traceability of the measurement of analytical parameters capable of evaluating the performance of methods is an important concept for the assessment of quality for the routine control, especially for residue monitoring of non-authorized medicinal substances in food from animal origin. The European Decision no. 657/2002/EC recommends to calculate two statistical limits, CCα and CCβ, which allow to evaluate the critical concentrations above which the method reliably distinguish and quantify a substance taking into account the variability of the method and the statistical risk to take a wrong decision. The calculation, which can be derived from the ISO standard no. 11843 is applied on a routine basis. An example displays a very simple way for evaluating the performance of an LC-MSMS method which has been validated a few years ago and is qualified onto a Micromass Quattro LCZ tandem mass spectrometer to monitor and confirm the nitrofuran metabolite residues in food from animal origin. Community Reference Laboratory for Antimicrobial Veterinary Drug Residue Control in Food from Animal Origin     

聚L－谷氨酸－炔诺酮肟酯复合体的制备

合成了聚Ｌ－谷氨酸－炔诺酮肟酯的复合体，炔诺酮的接入量为２２．８％．体外释放时间约１５大。     

Comparison of quantitative methods for analysis of polyphasic pharmaceuticals

Adequate very sensitive quantification methods are needed for the development and are also now required for the monitoring of undesirable solid form(s) as routine tests. The pre-requisite for quantitation are selectivity, sensitivity and most important the purity of standards and their proper storage, what is a challenge for metastable forms. Several analytical techniques are available such as X-ray diffraction, spectroscopy, thermal analysis and microcalorimetry. The different steps of the validation of the analytical methods and problems to be solved are discussed. Examples illustrate the different techniques and compare their possible advantages and limits. The relative standard deviation of measurements should allow for checking the homogenization procedure of mixtures for calibration. The validation should be carried out following ICH guidelines for validation of analytical methods. Comparison of different techniques in adequate concentration range add confidence in the analytical results.