中药生产过程质量控制关键技术研究进展

中医药发展已上升到国家战略层面,在医药行业贯彻实施"中国制造2025"战略的新形势下,中药生产过程质量控制是中药工业需要加快突破的关键领域之一。对中药生产过程质量控制领域在工艺设计、分析检测、过程建模、制造装备等方面的关键共性问题进行解析,综述了中药生产过程质量控制体系中工艺过程理解、生产过程实时分析方法开发、过程控制策略建立3个方面的研究进展;并结合企业研究实践,介绍了质量源于设计(quality by design,Qb D)、过程分析技术(process analytical technology,PAT)、实验设计(design of experiment,DOE)、多变量统计分析等关键技术在上述3个研究方向中的应用进展,分析了实际工业应用的难点问题并对其应用前景进行展望,旨在为中药企业应用和提升生产过程质量控制技术提供参考。     

表达谱基因芯片筛选体外循环前后心肌细胞因子的变化

Objestive Systemic inflarmmation may be triggered by injury, hypothermia, ischemia-reperfusion and the contact of the blood with foreign body during cardiopulmonary bypass (CPB). To determine the application values of gene chip technique in the clinical practice and the study of cardiovascular stagery, as well as to provide clues to the study of inflammatory responess during CPB, microarry for gene expression profiles was used to identify the differences in the gene expression of myocardium between pre-and post- CPB. Methods Six adult patients who underwent CPB from March to May in 2003 were involved. Samples of right atrium were col- lected before and at immediate end of CPB. BD AtlasTM cDNA Expression Arrays was used to identify the differences in the gene ex- pression of cytokines. The results were compared with that of semi-quantative RT-PCR. Resellts The mean age of 6 patients (5 males and 1 female) was (32.67± 11.72) years. The baseline heart function was gradeⅡin 3 cases and grade Ⅲ in 3 other cases. The baseline left ventricular ejection fraction(LVEF)was (58.17±7.91)%. The mere duration was (91.67±43.88) minutes for CPB and was (58.67±43.46) minutes for aorta blocking. The minimum nasopharynx/rectal temperture was (29.37±1.90)℃/ (32.15±1.52)℃. Gene expression profiles of cytokines in the myocardium pre- and post-CPB were analysed successfully. The ex- pression of IL-6, IFN-γ,Wnt5a, TNFRSF1B, a member of tumor necrosis factor receptor superfamily, PIGF and MFNG in the myo- cardium were unpregulated after CPB. Conclusion Microarray technique is applicable in the study of cytokines changes dying CPB. cDNA microarray identified pleliminarily the differences in the gene expression between pre- and post-CPB. These genes may be in- valved in inflammation and other psthophysiological responses incuced by CPB. The myocardiym is probably one of the major sources of cytokines during CPB. Further study may be helpful in understanding the llngthe development of inflammation during CPB, and eventually, reducing the post-operative complications.     

Suicide substrate reaction-diffusion equations: Varying the source

The suicide substrate reaction is a model for certain enzyme-inhibitingdrugs. This reaction system is examined assuming that the substratediffuses freely while the enzyme remains fixed. Two sets ofinitial and boundary conditions are examined: one modellingan instantaneous point source, akin to an injection of substrate,the other, a continuous point source, akin to a continuing influx,or intravenous drip, of substrate. The quasi-steady-state assumptionis applied to obtain analytical solutions for a limited parameterspace. Finally, further applications of numerical and analyticalexperimentation on pharmaceutical mechanisms are described.     

Association of a genetic polymorphism in human apolipoprotein B-100 with intermediate density lipoprotein concentrations

Immunochemical techniques have been used to identify five antigenic (Ag) sites on apolipoprotein B-100 (apoB), the major protein constituent of very low density (VLDL), intermediate density (IDL), and low density lipoproteins (LDL). Each Ag site results from allelic variation at a specific locus of the apoB gene. In the present study, we assessed whether variations in the five Ag loci were associated with concentrations of plasma lipids or lipoprotein fractions measured by analytical ultracentrifugation in a group of 44 healthy men. Pair-wise analyses of the Ag markers revealed that Ag(a1/d), in association with either Ag(x/y) or Ag(t/z), is significantly related to plasma IDL-mass concentrations. In this cohort we detected no significant associations of the Ag alleles (singly or in combination) with plasma total cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol, or mass of total VLDL or LDL. These results suggest that genetic variations in the apoB molecule may predispose to variations in concentrations of IDL that could have consequences for atherosclerotic risk.     

城市污灌废水的致突变性检测及色谱/质谱分析

应用Ames致突变试验,对比研究了武汉市易家墩、黄孝河污灌区污灌废水与土壤的致突变性。同时应用色谱/质谱(GC/MS)分析技术。测定了主要污水中有机污染物的化学组成。结果表明:罗家渠废水的致突变活性最强;受各条污水灌溉的土壤的致突变活性顺序与相应废水的强弱顺序一致;罗家渠废水中致突变致癌物主要是萘、联苯等。     

Neural classifier construction using regularization, pruning and test error estimation

In this paper we propose a method for construction of feed-forward neural classifiers based on regularization and adaptive architectures. Using a penalized maximum likelihood scheme, we derive a modified form of the entropic error measure and an algebraic estimate of the test error. In conjunction with optimal brain damage pruning, a test error estimate is used to select the network architecture. The scheme is evaluated on four classification problems.     

膳食纤维分析方法的简化

对ＳｅｌｖｅｎｄｒａｎＲＲ等人的冷中性洗涤剂纤维提取分析法（ＣＮＤＦ）进行简化，改变了各溶剂的处理时间，省去了湿球研磨与超声波处理步骤。将原法中ＳＬＳ－ＰＡＷ－ＤＷＳＯ处理时间１５ｈ，３０ｍｉｎ和１６ｈ分别延长为２２ｈ，４０ｍｉｎ与２２ｈ，化学分析与透射电镜观察结果表明，简化法对膳食纤维的提取分析效果与原推荐法相同，更加方便与实用。     

Penetration of pefloxacin and its desmethyl metabolite into the uroepithelium after a 800-MG single oral dose in human patients

Penetration of pefloxacin into the uroepithelium was studied in 20 patients (10 men and 10 women) receiving a single oral dose of 800 mg. Samples of serum, urine, and uroepithelium were taken 1.8 h (mean) after the dose. Pefloxacin and its active metabolite, norfloxacin, were assayed by liquid chromatography, and the microbiologically active compounds were quantified by a microbiological assay. Both procedures were correlated (r>0.7); nevertheless, slight differences detected in concentrations depended on the levels of norfloxacin achieved in the biological samples. The serum and tissue concentrations were higher than the concentration of bactericide (4 g·ml^–1), except in one case. The uroepithelium concentration of pefloxacin was proportional to the serum concentration (r=0.79). The urinary concentrations ranged from 1.2 g·ml^–1 to 82.4 g·ml^–1. The mean norfloxacin/pefloxacin ratios were 3% in serum, 8% in uroepithelium, and 44% in urine. The mean uroepithelium/serum concentration ratios were 1 for pefloxacin and 2.3 for norfloxacin. This result shows that, at a time close to that of the maximum concentration, there is good penetration of pefloxacin and norfloxacin into the uroepithelium.     

Drug effects on clinical laboratory tests

Drugs and xenobiotics can affect clinical laboratory test results either by interfering with the analytical systems themselves, or by influencing endogenous constituents. National and international bodies have brought widespread recognition to this problem and have proposed protocols for its thorough scientific study. In this survey the authors discuss studies in their laboratories concerning the effects of drugs on thousands of patients undergoing a routine clinical screen. A database is described for storing both patient information and a detailed analysis of the published literature on drug effects. Analytical interferences in clinical tests must be examined in validating the procedure. However, highly specific analytical techniques are increasingly helping to reduce such interferences. Biological effects can be classified as physiological, pharmacological or toxicological. In some cases, biological effects can be used to advantage in monitoring treatment by potentially hazardous drugs, such as the cardiac glycosides. The requirement for a well-defined reference population for each drug and for access to all clinical and medical data for each patient is discussed. The need for greater awareness of the influence of drugs on clinical laboratory results is considered, together with the suggestion that the health professions should try to exploit such effects in monitoring possible toxicity problems, in defining genetic constitution and in designing medication programmes.