湖北省原料药GMP认证中发现的主要缺陷及建议

目的：为全面理解原料药GMP认证相关标准,提高生产企业对原料药生产规范的认识和检查员的检查水平。方法：对2016年至2017年湖北省原料药现场检查中主要缺陷进行统计分析,对GMP认证中主要缺陷项目进行分类总结。结果与结论：通过共性问题,结合原料药产品的本身特点,建议加强各岗位操作人员培训,落实培训效果;合理设计厂房,加强硬件系统的改造;严格把关物料,做好溶剂回收工作;注重细节,有针对性做好确认与验证工作;文件管理系统化,记录填写规范化;引入风险管理,贯彻执行生产全过程管理;重视变更和偏差管理,提高质量意识;建立职业化检查员队伍。     

海藻羊栖菜质量研究综述

目的 了解海藻羊栖菜中功效成分及外源性有害物质的分类情况,以及它们的分析方法研究进展,为本领域研究人员提供参考。方法 采用综述的方法对近几年来海藻羊栖菜的相关研究文献进行梳理。结果 主要从组成成分及外源性有害物质等方面对羊栖菜的研究进行了分析。将上述物质分别从分类、提取和检测方法等方面进行研究。结论 药食同源品种日益受到人们的关注,但目前我国中药标准不够完善,尤其对有害物质的研究仍然缺乏,建议加快相关标准的拟定。     

A national survey: percussion, vibration, shaking and active cycle breathing techniques used in patients with acute exacerbations of chronic obstructive pulmonary disease

Objectives

Chronic obstructive pulmonary disease (COPD) is a frequent cause of hospital admission in older people. There is a perception that manual chest physiotherapy techniques are commonly used in the treatment of patients admitted with acute exacerbations of COPD (AECOPD). However, it is not clear which chest physiotherapy techniques benefit patients admitted with AECOPD, or even which techniques are currently being employed. The aim of this study was to investigate the use of percussion, vibration, shaking and active cycle breathing techniques (ACBT) by physiotherapists working in respiratory care and treating patients admitted with AECOPD.

Design

A postal questionnaire was used to survey physiotherapists working in respiratory care in 190 acute hospital trusts in the UK about chest clearance physiotherapy techniques used in the treatment of patients admitted with AECOPD.

Results

Of the 190 questionnaires mailed, 146 (77%) complete responses were received. One hundred and twenty-nine (88%) respondents reported that they always or often used ACBT, compared with 38 (26%), 16 (11%) and 12 (8%) respondents for vibration, shaking and percussion, respectively. The differences were statistically significant: ACBT used always/often versus vibration used always/often (χ² = 5.8, P = 0.01); ACBT used always/often versus percussion used always/often (χ² = 8.3, P < 0.0001); and ACBT used always/often versus shaking used always/often (χ² = 6.7, P < 0.001).

Conclusions

Manual chest physiotherapy techniques (vibration, percussion and shaking) were used infrequently for chest clearance in patients admitted with AECOPD, whereas ACBT was used always or often by 88% of responders.     

Lapatinib nano-delivery systems: a promising future for breast cancer treatment

Introduction: Breast cancer stands the second prominent cause of death among women. For its efficient treatment, Lapatinib (LAPA) was developed as a selective tyrosine kinase inhibitor of receptors, overexpressed by breast cancer cells. Various explored delivery strategies for LAPA indicated its controlled release with enhanced aqueous solubility, improved bioavailability, decreased plasma protein binding, reduced dose and toxicity to the other organs with maximized clinical efficacy, compared to its marketed tablet formulation.

Areas covered: This comprehensive review deals with the survey, performed through different electronic databases, regarding various challenges and their solutions attained by fabricating delivery systems like nanoparticles, micelle, nanocapsules, nanochannels, and liposomes. It also covers the synthesis of novel LAPA-conjugates for diagnostic purpose.

Expert opinion: Unfortunately, clinical use of LAPA is restricted because of its extensive albumin binding capacity, poor oral bioavailability, and poor aqueous solubility. LAPA is marketed as the oral tablet only. Therefore, it becomes imperative to formulate alternate efficient multiparticulate or nano-delivery systems for administration through non-oral routes, for active/passive targeting, and to scale-up by pharmaceutical scientists followed by their clinical trials by clinical experts. LAPA combinations with capecitabine and letrozole should also be tried for breast cancer treatment.     

Continuous flow technology vs. the batch-by-batch approach to produce pharmaceutical compounds

Introduction: For the manufacture of small molecule drugs, many pharmaceutical innovator companies have recently invested in continuous processing, which can offer significant technical and economic advantages over traditional batch methodology. This Expert Review will describe the reasons for this interest as well as many considerations and challenges that exist today concerning continuous manufacturing.

Areas covered: Continuous processing is defined and many reasons for its adoption are described. The current state of continuous drug substance manufacturing within the pharmaceutical industry is summarized. Current key challenges to implementation of continuous manufacturing are highlighted, and an outlook provided regarding the prospects for continuous within the industry.

Expert commentary: Continuous processing at Lilly has been a journey that started with the need for increased safety and capability. Over twelve years the original small, dedicated group has grown to more than 100 Lilly employees in discovery, development, quality, manufacturing, and regulatory designing in continuous drug substance processing. Recently we have focused on linked continuous unit operations for the purpose of all-at-once pharmaceutical manufacturing, but the technical and business drivers that existed in the very beginning for stand-alone continuous unit operations in hybrid processes have persisted, which merits investment in both approaches.     

基于大鼠体内多成分代谢的黄芪质控成分遴选

目的 基于中药多成分作用特点,探讨黄芪多成分在体内的代谢情况,遴选黄芪质控成分。方法 制备黄芪水提物,ig给予大鼠（生药20 g/kg）,每天3次,连续给药3 d,腹主动脉采血、代谢笼收集尿液,结合超高效液相色谱-串联质谱（UPLC-MS/MS）技术对黄芪水提物主要成分、入血成分和尿液排泄成分进行鉴别,并分析主要的代谢途径,遴选黄芪质控成分。结果 黄芪水提物主成分共鉴别出包括毛蕊异黄酮葡萄糖苷、芒柄花苷、calycosin-7-O-glc-6"-O-malonate、毛蕊异黄酮、芒柄花素等在内的15个化合物;血浆样品中指认出11个成分,包括7个代谢成分和4个原型成分;尿液样品中指认出14个成分,9个代谢成分及5个原型成分。结论 根据质谱数据分析结果,遴选出黄芪中以原型入血的成分和参与体内代谢的成分,包括毛蕊异黄酮葡萄糖苷、芒柄花苷、毛蕊异黄酮、芒柄花素、大豆苷元、3-hydro-9,10-diMP、isomer of 3-hydro-9,10-diMP、calycosin-7-O-glc-6"-O-acetate和formononetin-7-O-glc-6"-O-acetate,作为黄芪的质控成分。     

Mangiferin and its aglycone,norathyriol, improve glucose metabolism by activation of AMP-activated protein kinase

Context: Mangiferin has been reported to possess antidiabetic activities. Norathyriol, a xanthone aglycone, has the same structure as mangiferin, except for a C-glucosyl bond. To our best knowledge, no study has been conducted to determine and compare those two compounds on glucose consumption in vitro.

Objective: In this study, the effects of norathyriol and mangiferin on glucose consumption in normal and insulin resistance (IR) L6 myotubes were evaluated. Simultaneously, the potential mechanism of this effect was also investigated.

Materials and methods: Normal or IR L6 myotubes were incubated with norathyriol (2.5?～?10?μM, 0.625?～?2.5?μM), mangiferin (10?～?40?μM, 2.5?～?10?μM) or rosiglitazone (20?μM) and/or 0.05?nM insulin for 24?h, respectively. The glucose consumption was assessed using the glucose oxidase method. Immunoblotting was performed to detect protein kinase B (PKB/Akt) and AMP-activated protein kinase (AMPK) phosphorylation in L6 myotubes cells.

Results: Norathyriol and mangiferin treatment alone increased the glucose consumption 61.9 and 56.3%, respectively, in L6 myotubes and made additional increasing with 0.05?nM insulin. In IR L6 myotubes, norathyriol treatment made increasing with or without insulin, mangiferin treatment also made increasing but only when co-treated with insulin. Immunoblotting results showed that norathyriol and mangiferin produced an increase of 1.9?- and 1.8-fold in the phosphorylation levels of the AMPK, but not in Akt.

Discussion and conclusion: Our findings suggest that norathyriol and mangiferin could improve the glucose utilization and insulin sensitivity by up-regulation of the phosphorylation of AMPK. Norathyriol may be considered as an active metabolite responsible for the antidiabetic activity of mangiferin.     

Novel Tools to Improve Patient Selection and Monitoring on Active Surveillance for Low-risk Prostate Cancer: A Systematic Review

Context

Active surveillance (AS) is an alternative to initial radical treatment of low-risk prostate cancer (PCa). Current criteria for selection and follow-up incorrectly exclude some patients eligible for AS and misclassify some who actually harbour significant disease. Better prediction of cancer behaviour at diagnosis would allow less strict monitoring and may improve acceptance of AS.

Objective

To review and critically analyse the literature on the value of novel clinical tools for patient selection and monitoring on AS.

Evidence acquisition

A comprehensive search of the PubMed database until July 10, 2013, was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analysis statement guidelines. Studies assessing novel markers and diagnostics for patient selection for AS and follow-up during AS were included. Studies analysing only classic clinical parameters used in current protocols (prostate-specific antigen, prostate volume, number of (positive) prostate biopsies, percentage malignant tissue, Gleason score) were excluded. This review focuses only on the AS setting and not on predicting insignificant disease in general.

Evidence synthesis

Of 787 studies on AS, 30 were included in this review: 14 on magnetic resonance imaging (MRI), 5 on serum markers, 5 on urinary markers, 4 on histopathology markers, and 2 on germline genetic markers. Several of these markers improve the prediction of tumour volume, tumour grade, or time to active treatment. MRI has a high specificity for low-risk PCa; new serum markers are associated with unfavourable disease. In none of the studies was the new marker used as the primary decision tool. Long-term outcome measures such as mortality were not assessed. The definition of indolent PCa is disputable.

Conclusions

Imaging and serum markers may improve future patient selection for AS and follow-up during AS. Prospective studies should aim to further evaluate the clinical utility of these new markers with respect to longer term outcomes of AS.

Patient summary

We searched the literature for articles reporting new ways to safely monitor low-risk prostate cancer for patients who have not had radical treatment. We found 30 articles. The most promising tools appear to be magnetic resonance imaging scans and various new blood markers. These may be used in the future within active surveillance regimens.