The development of coatings using combinatorial/high throughput methods: a review of the current status

Combinatorial chemistry is a relatively new experimental methodology developed by academics and researchers in the pharmaceutical industry to reduce the time and cost associated with drug development. Basically, combinatorial chemistry involves the rapid synthesis and evaluation of large numbers of compounds in parallel using robotics, rapid analytical instrumentation, and data management software. More recently, the principles of combinatorial chemistry have been applied to materials development, and interest in this area is increasing rapidly. This interest can be attributed to the potential for obtaining a major competitive advantage by implementing a combinatorial approach. This document provides an introduction to combinatorial materials science and provides a review of efforts aimed at developing combinatorial workflows for coating development. While the application of combinatorial methods to coating development is still in its infancy, full combinatorial workflows have been developed within a few different organizations. Presented at the 2006 FutureCoat! conference, sponsored by the Federation of Societies for Coatings Technology, in New Orleans, LA, on November 1–3, 2006.     

Process considerations for the scale-up and implementation of biocatalysis

With increasing emphasis on renewable feed-stocks and green chemistry, biocatalytic processes will have an important role in the next generation of industrial processes for chemical production. However, in comparison with conventional industrial chemistry, the use of bioprocesses in general and biocatalysis in particular is a rather young technology. Although significant progress has been made in the implementation of new processes (especially in the pharmaceutical industry) no fixed methods for process design have been established to date. In this paper we present some of the considerations required to scale-up a biocatalytic process and some of the recently developed engineering tools available to assist in this procedure. The tools will have a decisive role in helping to identify bottlenecks in the biocatalytic development process and to justify where to put effort and resources.     

Computational Chemistry in the Pharmaceutical Industry: From Childhood to Adolescence

Computational chemistry within the pharmaceutical industry has grown into a field that proactively contributes to many aspects of drug design, including target selection and lead identification and optimization. While methodological advancements have been key to this development, organizational developments have been crucial to our success as well. In particular, the interaction between computational and medicinal chemistry and the integration of computational chemistry into the entire drug discovery process have been invaluable. Over the past ten years we have shaped and developed a highly efficient computational chemistry group for small‐molecule drug discovery at Bayer HealthCare that has significantly impacted the clinical development pipeline. In this article we describe the setup and tasks of the computational group and discuss external collaborations. We explain what we have found to be the most valuable and productive methods and discuss future directions for computational chemistry method development. We share this information with the hope of igniting interesting discussions around this topic.     

Computational chemistry, data mining, high-throughput synthesis and screening - informatics and integration in drug discovery

Drug discovery today includes considerable focus of laboratory automation and other resources on both combinatorial chemistry and high-throughput screening, and computational chemistry has been a part of pharmaceutical research for many years. The real benefit of these technologies is beyond the exploitation of each individually. Only recently have significant efforts focused on effectively integrating these and other discovery disciplines to realize their larger potential. This technical note will describe one example of these integration efforts.     

Managing laboratory automation: integration and informatics in drug discovery

Drug discovery today requires the focused use of laboratory automation and other resources in combinatorial chemistry and high-throughput screening (HTS). The ultimate value of both combinatorial chemistry and HTS technologies and the lasting impact they will have on the drug discovery process is a chapter that remains to be written. Central to their success and impact is how well they are integrated with each other and with the rest of the drug discovery processes-informatics is key to this success. This presentation focuses on informatics and the integration of the disciplines of combinatorial chemistry and HTS in modern drug discovery. Examples from experiences at Neurogen from the last five years are described.     

Implementation of analytical technologies in a pharmaceutical development organization looking into the next millennium

Managing the implementation of new technology in a pharmaceutical development environment has provided challenges and opportunities to obtain benefits from technologies, e.g. laboratory automation. Successful application of new techniques requires a dedicated resource. Within Pharmaceutical Technologies, this was initially a single person, who has since evolved into a team dedicated to the investigation and development of robotics and non-invasive analytical techniques. Pharmaceutical development is an important interface between research and commercial manufacturing. In research, the success of genomics and combinatorial chemistry will result in a significant increase in the number of development compounds, and this, combined with the desire of commercial manufacturing to move towards parametric release, puts an emphasis on the need for rapid analytical methods. Some ideas on the techniques that will be required to meet these goals will be described together with their impact on automation.     

Principles and Design Strategies for Ultra-efficient Production Systems in the Process Industry

A sustainable design of production systems, both within and beyond company boundaries, is essential for the future viability of the process industry. In this context, the concept of ultra-efficiency has recently been developed, aiming at achieving holistic improvements in the fields of action energy and material efficiency, emission reduction, organization, human and staff, with the goal of establishing a positive impact factory. In this paper, the concept developed mainly for the discrete manufacturing industry is transferred to the process industry. It is put into the scientific sub context and elementary approaches, methods and strategies for factory planning and design of production processes in the process industry are summarized.     

关于提高有机化学教学效果的探讨

医药和生物行业的迅速发展推动着有机化学的发展,大学有机化学的学习对于今后从事医药、化工、生物等行业显得尤为重要。针对有机化学教学的现状以及存在的问题,从如何提高学生对有机化学学习的兴趣以及有机化学知识点和内容的落实等方面考虑,探讨提高有机化学教学效果的方法。     

Virtual Combinatorial Chemistry and Pharmacological Screening: A Short Guide to Drug Design

Traditionally, drug development involved the individual synthesis and biological evaluation of hundreds to thousands of compounds with the intention of highlighting their biological activity, selectivity, and bioavailability, as well as their low toxicity. On average, this process of new drug development involved, in addition to high economic costs, a period of several years before hopefully finding a drug with suitable characteristics to drive its commercialization. Therefore, the chemical synthesis of new compounds became the limiting step in the process of searching for or optimizing leads for new drug development. This need for large chemical libraries led to the birth of high-throughput synthesis methods and combinatorial chemistry. Virtual combinatorial chemistry is based on the same principle as real chemistry—many different compounds can be generated from a few building blocks at once. The difference lies in its speed, as millions of compounds can be produced in a few seconds. On the other hand, many virtual screening methods, such as QSAR (Quantitative Sturcture-Activity Relationship), pharmacophore models, and molecular docking, have been developed to study these libraries. These models allow for the selection of molecules to be synthesized and tested with a high probability of success. The virtual combinatorial chemistry–virtual screening tandem has become a fundamental tool in the process of searching for and developing a drug, as it allows the process to be accelerated with extraordinary economic savings.     

两化融合环境下智能工厂探索与实践

随着新一代信息技术的飞速发展,以“绿色智能”为核心的第四次工业革命正悄然兴起,从而为传统石化行业带来了巨大挑战与机遇。智能化发展成为石化企业转型升级的必然选择。为此,惠州石化积极响应《中国制造2025》,开展了智能工厂探索实践,提出以两化融合引领企业智能化进程的实施策略,开展基于工业互联网的工业大数据集成创新,研究形成智能炼厂的应用框架和实施内容,组织开展智能化的创新应用,取得了良好成效。同时指出推进新一代智能应用的主攻方向,为石化行业乃至流程行业智能工厂的建设提供了借鉴,形成具有中国海油特色的石化企业智能工厂示范效应。     

Preliminary experiments on metallisation of ceramic oxide superconductors

Abstract

The present paper briefly reports on preliminary experiments on two new methods for the metallisation of ceramic oxide high temperature superconductors )HTS compounds): sinter-permeate silver and chemically precipitated silver. By using well characterised HTS samples for the measurement of superconducting properties it is shown that successful metallisation and jointing were obtained. The two methods are considered to have potential for further development and application in this field.     

医药开发新动向及印度公司面临的挑战

许多医药公司在采用生物信息技术、计算机技术和组合化学方法开发新品种医药,但重要的是首先要找到主要化合物,研究的重点应更多地放在示构药物设计方面。近几年,印度公司在开发新医药品方面作了大量的工作,但也存在资金和人员不足的问题。在印度,每1分钟就有1人死于结核病,急需开发治疗结核病的新药。目前,基因技术的应用将引起新药物开发的进一步变革。     

Combinatorial strategies for targeting protein families: application to the proteases

Tens of thousands of proteins have been identified as a result of recent large scale genomic and proteomic efforts. With this large influx of new proteins, the formidable task of elucidating their function begins. However, this task becomes more manageable if proteins are divided into families based upon sequence homology, thereby allowing tools for their systematic study to be developed based upon their common structural and mechanistic characteristics. Combinatorial chemistry is ideally suited for the systematic study of protein families because a large amount of diversity can be readily displayed about a common scaffold designed to target a given protein family. Targeted combinatorial libraries have been particularly effective for the study of a ubiquitous family of proteins, the proteases. Substrate-specificity profiles of many proteases have been determined by using combinatorial libraries of appropriately labeled peptides. This specificity information been utilized to identify the physiological protein substrates of these enzymes and has facilitated inhibitor design efforts. Furthermore, combinatorial libraries of small molecules prepared with mechanism-based scaffolds have resulted in the identification of potent, small-molecule inhibitors of numerous proteases. Cell-permeable small-molecule inhibitors identified by these methods have served as powerful chemical tools to study protease function in vitro and in vivo and have served as leads for the development of therapeutic agents.     

Nanocrystal technology for drug formulation and delivery

With the development of modern technology like high throughput screening, combinatorial chemistry and computer aid drug design, the drug discovery process has been dramatically accelerated. However, new drug candidates often exhibit poor aqueous or even organic medium solubility. Additionally, many of them may have low dissolution velocity and low oral bioavailability. Nanocrystal formulation sheds new light on advanced drug development. Due to small (nano- or micro- meters) sizes, the increased surface-volume ratio leads to dramatically enhanced drug dissolution velocity and saturation solubility. The simplicity in preparation and the potential for various administration routes allow drug nanocrystals to be a novel drug delivery system for specific diseases (i.e. cancer). In addition to the comprehensive review of different technologies and methods in drug nanocrystal preparation, suspension, and stabilization, we will also compare nano- and micro-sized drug crystals in pharmaceutical applications and discuss current nanocrystal drugs on the market and their limitations.     

关于绿色煤化工发展的探索和思考

介绍了我国煤化工产业的发展现状;从思维、产品、技术、能耗等方面分析了新型煤化工的特点;指出发展新型绿色煤化工是实现煤炭资源清洁、高效、环保利用的有效途径,是今后我国煤化工产业的发展方向。     

制药行业有机废气催化燃烧研究进展

制药行业在我国快速发展,带来经济增长与生活便利的同时也带来了大量挥发性有机污染物（VOCs）的排放。针对制药行业废气排放量大、排放节点多、污染物种类复杂等特点,催化燃烧因经济环保、应用灵活,成为处理制药VOCs的合适选择。本文总结了制药行业排放的典型VOCs及常见医用药品生产过程中的特征污染物,并着重从催化燃烧催化材料研发及应用的角度,总结了近年来制药行业典型VOCs催化燃烧技术的研究现状,同时对我国制药行业有机废气治理作了展望,即需进一步加深制药行业VOCs排放特征、VOCs实验室治理等基础研究来保证实际治理过程中的经济有效性;同时在原有催化氧化催化剂研究的基础上,研发多技术耦合工艺,实现制药行业废气的达标排放。     

Measurement error correction using validation data: a review of methods and their applicability in case-control studies

Measurement error is a serious problem in the analysis of epidemiological data. In the past 20 years, a large number of methods for the correction of measurement error have been developed. While at the beginning mostly methods for cohort studies were considered, recently more attention has been paid to case-control studies. Although a variety of methods have been proposed, they are very rarely used in practice. To stimulate their use and further development, this article provides a comprehensive overview on methods developed for multivariable regression analysis of epidemiologic studies with validation data sets. The methods are systematically classified with respect to the underlying theory. An assessment of prerequisites, assumptions and performance of the available methods is given. Particular attention is paid to applicability to case-control studies and need for further research and development is pointed out.     

纯化水系统中灭菌方法的应用及比较

分别采用二氧化氯溶液和臭氧水溶液对制药厂纯化水系统的贮罐和管道进行灭菌处理,比较灭菌效果和操作过程,最终认定臭氧水溶液灭菌方法在灭菌效率和水资源节约等方面优于二氧化氯溶液,适用于制药厂水系统管路、贮罐的灭菌处理.     

药物化学课程双语教学的探讨

药物化学课程是药学专业重要的必修专业课程之一,对于药学学生综合能力的培养具有重要的意义。然而,随着与国外化学制药行业的接轨,我国化学制药企业迫切需要精通外语的药物化学专业人才,故药物化学课程双语教学势在必行。对药物化学课程开展双语教学,文章从教材、教学方法、师资队伍和学生成绩考核等多方面进行了探讨。     

绿色化学技术在制药工业中的应用

绿色化学是当今国际化学研究的前沿，是21世纪的科学，并将成为各化学基础学科和应用技术研究的热点。本文综述了几种绿色化学技术在制药工业中的应用及进展．并指出了绿色化学是我国制药工业可持续发展的必由之路。