Establishment of Microbial Limit Test Methods for Two Hospital Preparations

[Objectives] This study was conducted to establish microbial limit test methods for traditional Chinese medicine preparations Yunpi Granules and Bupi Qiangli Paste. [Methods] According to General Rules of Part IV of Chinese Pharmacopoeia, applicability tests were conducted on microbial limit test methods for the above two traditional Chinese medicine preparations by the plate method. [Results] The established methods showed recovery values in the range of 0.5-2.0 for both experimental strains, and the control bacteria could be detected in the experimental group, but not in the negative control group. [Conclusions] The microbial limit test methods were reliable for the two traditional Chinese medicine preparations and could be used for quality control.

Applicability of Microbial Limit Test Method for Qingyan Zhisou Powder

[Objectives]This study was conducted to establish a microbial limit test method for Qingyan Zhisou Powder.[Methods]Applicability tests were carried out according to Microbial Limit Tests of Non-sterile Products,General Rules 1105-1107 of Part IV of Chinese Pharmacopoeia,2020.[Results]Qingyan Zhisou Powder had a strong bacteriostatic effect on Pseudomonas aeruginosa.After increasing the dilution ratio(1:40),the bacteriostatic effect was obviously eliminated.When the total number of aerobic microbes was determined by the test liquid dilution method(1:40),the recovery values were in the range of 50%-200%;and when using the test liquid(1:10)to determine the total number of mold and yeasts,the recovery ranged from 50%to 200%.Escherichia coli,Salmonella and bile-tolerant Gram-negative bacteria were detected by both the routine method and dilution method in experimental groups.[Conclusions]The microbial limit test of Qingyan Zhisou Powder adopted the test liquid dilution method,and the routine method could be used for the test of Escherichia coli,Salmonella and bile-tolerant Gram-negative bacteria.The applicability test of the method is feasible,with scientific and accurate results,and the method can effectively control the quality of the preparation and is recommended for popularization.

Validation of Microbial Limit Test Methods of Tongmai Tangyanming Capsule

[ Objectives] This study was conducted to establish a method for microbial limit test of Tongmai Tangyanming Capsule. [ Methods] According to the Chinese Pharmacopoei 2015 edition of the four general rules, the microbiological limits of non-sterile products were verified. [ Results] Tongmai Tangyanming Capsule has a strong inhibitory effect on Bacillus subtilis and Candida albicans. The antimicrobial activity was significantly eliminated after increasing the diluent （ 1 ： 20） ; and the recoveries were in the range of 0.5 -2 when the total quantities of aerobic microbes were determined by dilution method （1：20）. When the total quantities of mould and yeast were determined by dilution method （1：20）, the recoveries were from 0.5 to 2, and Escherichia coli, cholate-tolerant Gram-negative bacteria and Salmonella can be detected by the test solution dilution method. [ Condusions] With the plate method, the total quantities of aerobic bacteria and the quantities of mould and yeast were examined by increasing diluent, and conventional method was used for examination of control bacteria including E. coli, cholatetolerant Gram-negative bacteria and Salmonella. This method has been proved effective for microbial limit test of Tongmai Tangyanming Capsule, and can effectively control the quality of the preparation. The method is accurate and reliable.

Validation of Microbial Limit Test Methods of Compound Gangbangui Capsule

[Objectives] This study was conducted to establish a method for microbial limit test of Compound Gangbangui Capsule. [Methods] According to the Chinese Pharmacopoei 2015 edition of the four general rules,the microbiological limits of non-sterile products were verified. [Results]Compound Gangbangui Capsule has a strong inhibitory effect on S. aureus,and the antimicrobial activity was significantly eliminated after increasing the diluent（ 1∶ 20）; and the recoveries were in the range of 0. 5-2. 0 when the total quantities of aerobic microbes were determined by dilution method（ 1∶ 20）. When the total quantities of mould and yeast were determined by conventional method（ 1∶ 20）,the recoveries were from 0. 5 to 2. 0,and Escherichia coli can be detected in experimental groups by the test solution dilution method. [Conclusions]With the plate method,the total quantities of aerobic bacteria and the quantities of mould and yeast were examined by increasing diluent and conventional method,respectively,and control bacteria,E. coli was examined by conventional method. This method has been proved effective for microbial limit test of Compound Gangbangui Capsule,and can effectively control the quality of the preparation. The method is accurate and reliable.

Validation for Microbial Limit Test Method of Compound Yu E Nose Drops

[Objectives] This study was conducted to establish a method for microbial limit test of Compound Yu E Nose Drops.[Methods] According to the Chinese Pharmacopoei (General Rules in the fourth part of the 2015 edition),the microbial limit test method for Compound Yu E Nose Drops was verified.[Results] Compound Yu E Nose Drops has a strong inhibitory effect on Staphylococcus aureus and Bacillus subtilis,and the inhibitory activity was significantly eliminated after increasing the diluent (1∶ 20).The recoveries were all in the range of 0.5-2.0 when the total quantities of aerobic microbes were determined by the dilution method (1∶ 20).When the total quantities of mould and yeast were determined by the conventional method,the recoveries were both in the range of 0.5-2.0.When examining control bacteria,Escherichia coli,S.aureus and Pseudomonas aeruginosa can all be detected in the test groups by the test liquid dilution method.[Conclusions] For Compound Yu E Nose Drops,the total quantities of aerobic microbe can be counted by the dilution method;the quantities of mould and yeast can be examined by the conventional plate method;and the conventional method can be used for control microbe examination.

Cautionary Remarks When Testing Agreement between Two Raters for Continuous Scale Measurements: A Tutorial in Clinical Epidemiology with Implementation Using R

Background: When continuous scale measurements are available, agreements between two measuring devices are assessed both graphically and analytically. In clinical investigations, Bland and Altman proposed plotting subject-wise differences between raters against subject-wise averages. In order to scientifically assess agreement, Bartko recommended combining the graphical approach with the statistical analytic procedure suggested by Bradley and Blackwood. The advantage of using this approach is that it enables significance testing and sample size estimation. We noted that the direct use of the results of the regression is misleading and we provide a correction in this regard. Methods: Graphical and linear models are used to assess agreements for continuous scale measurements. We demonstrate that software linear regression results should not be readily used and we provided correct analytic procedures. The degrees of freedom of the F-statistics are incorrectly reported, and we propose methods to overcome this problem by introducing the correct analytic form of the F statistic. Methods for sample size estimation using R-functions are also given. Results: We believe that the tutorial and the R-codes are useful tools for testing and estimating agreement between two rating protocols for continuous scale measurements. The interested reader may use the codes and apply them to their available data when the issue of agreement between two raters is the subject of interest.

赤丹丸微生物限度检查方法适用性研究

目的建立医院制剂赤丹丸的微生物限度检查方法。方法根据四部通则1105-1107,2020年版《中国药典》的规定,采用常规法和稀释法计算赤丹丸中各个菌株的回收比,并对控制菌进行检查。结果赤丹丸有较强的抑菌性,当采用1∶100稀释法时,各试验菌株的回收比均在0.5~2范围内,常规法检出相应的控制菌。结论赤丹丸采用1∶100稀释法用于需氧菌总数、霉菌及酵母菌总数的计数,常规法用于控制菌的检查。

基于虚拟仿真技术的微生物限度检查教学资源建设

针对中药饮片微生物限度检查实训教学中遇到的问题,以学生为中心,创设职业情境,设计开发虚拟仿真实训教学软件及配套数字化活页式实训手册。高质量的数字教学资源,能够增强学生学习体验感,引导学生积极探索与思考,提高学生创新能力。

钢壳沉管隧道耐火极限标准与防火保护技术研究——以深中通道沉管隧道为例

为提高我国超大断面钢壳沉管隧道火灾防控水平,以深中通道海底沉管隧道为例,采用热力耦合模拟和材性试验等方法开展钢壳沉管隧道耐火极限标准研究,考虑到龙骨、拼缝等防火构造薄弱环节,进行管节结构和管节接头耐火试验,并提出相应的防火保护技术方案。主要结论如下:1)管节结构的耐火极限标准为火灾时,应将结构内侧钢壳最高温度控制在300℃以内;2)OMEGA橡胶管节接头的耐火极限标准为OMEGA橡胶超过70℃的时间小于2 h,超过100℃的时间小于1 h,且最高温度不得超过150℃;3)GINA橡胶管节接头的耐火极限标准为GINA橡胶超过100℃的时间小于1 h,且最高温度不得超过150℃;4)管节结构可采用35 mm单层防火板L型拼缝,对接面涂热膨胀胶;5)管节接头可采用35 mm防火板+50 mm陶瓷纤维毯双层防火保护体系,龙骨自由端取500 mm,拼缝处采用防火胶封堵。

高液限红黏土用作路基填料的改良方法研究

为解决广西玉湛高速公路中高液限红黏土难以作为路基填料的技术难题,本文对该地区红黏土的物理力学性质进行了试验研究,并且开展了掺加河砂、山脚砂和消石灰的3种红黏土改良试验研究。研究结果表明:随着掺砂量的增大,掺河砂改良红黏土的液限、塑限、塑性指数和毛细管水上升高度都随之降低,而加州承载比CBR值随之增大;当掺砂量为15%时,掺河砂改良红黏土的液限和CBR值都满足规范要求,可以作为高速公路下路堤填料,但是如果作为高速公路上路堤和路床的填料,则需要进一步提高掺砂量。随着掺砂量的增大,掺山脚砂改良红黏土的最优含水率、液限、塑限、塑性指数随之降低,而最大干密度和CBR值随之增大;掺砂量为30%时,掺山脚砂改良红黏土的CBR值、液限和塑性指数都满足规范要求,可以作为路基填料。掺加4%消石灰时,红黏土的CBR值、液限和塑性指数虽都满足相关规范关于路基填料的要求,但是液限已非常接近规范限值,因此建议消石灰掺量取6%。现场填筑试验段结果表明,掺山脚砂或掺加消石灰改良高液限红黏土的方案都是可行的,改良土的液限、塑限、塑性指数和CBR值都有明显的改善,均可作为高速公路路基的填料。

基于上限定理确定隧道式锚碇极限抗拔承载力

隧道式锚碇作为一种新型的悬索桥锚碇结构,因具有因地制宜、经济环保的优点在多山的西南地区得到了广泛应用。已有研究表明,锚塞体围岩性质较差、埋深较浅,锚塞体与围岩接触界面结合程度较好的隧道式锚碇极易发生倒楔形冲切破坏。将破坏体视为以锚塞体中心线为轴线的旋转楔形体,假定破坏面为最小旋转曲面,利用变分法经典欧拉方程求解破坏体最小旋转曲面问题,确定旋转曲面母线方程;基于改进的Mohr-Coulomb强度准则,由主缆拉拔荷载和楔形体自重所做的外功率与楔形体沿滑移面所消耗的内功率相等的条件建立虚功方程,推导隧道式锚碇极限抗拔承载力上限解。开展隧道式锚碇室内模型试验,研究了拉拔承载过程中的坡面位移的变化规律及隧道式锚碇的破坏模式。研究结果表明,拉拔作用点的荷载-位移曲线可分为4个阶段:克服重力阶段、弹性阶段、弹塑性阶段以及破坏阶段;隧道式锚碇破坏模式为围岩倒楔形冲切破坏,破坏体可近似视为以锚塞体中心线为轴线的旋转楔形体;由推导公式得到的隧道式锚碇极限抗拔承载力计算值与实测值一致性较好,具有一定的可靠性,可为隧道式锚碇的设计提供参考。

午时茶颗粒微生物限度检查方法的验证

按照《中华人民共和国药典》(2020年版四部)要求,采用平皿倾注法(1∶10,1∶20,1∶50,1∶100)和常规培养基体积直接接种法对午时茶颗粒进行微生物计数方法和控制菌检查方法适用性试验,通过计算3批次的试验菌回收比值筛选需氧菌总数计数、霉菌和酵母菌总数计数方法.当采用平皿倾注法(1∶10)时,各试验菌回收比值均在0.5~2.0范围内.控制菌阳性对照组生长良好,经革兰氏染色显微镜检查和生化鉴定试验,符合试验菌形态学和生化特性.研究建立的方法准确可行,重现性好,可用于午时茶颗粒的微生物限度检查.

于氏解郁调肝散微生物限度检测方法考察

(目的)建立于氏解郁调肝散的微生物限度检测方法,加强于氏解郁调肝散的质量控制。(方法)依据2020版《中国药典》中非无菌制剂微生物限度检测法进行方法适用性考察。(结果)采用1∶1000稀释法测定需氧菌总数,采用1∶10稀释法测定霉菌和酵母菌总数,各实验菌回收率在0.5~2之间;三种控制菌大肠埃希菌、沙门菌、耐胆盐革兰阴性菌均可采用常规接种法,结果符合要求。(结论)研究建立的微生物限度检测方法,准确、重复性好,可用于于氏解郁调肝散的质量控制,为完善于氏解郁调肝散的质量标准提供了重要数据支持。

振动试验量级异常波动的机理及解决方法

针对振动试验行业内试验控制量级大幅波动的异常现象,进行了控制原理分析,根据分析结果进行了试验验证,试验完全复现了控制量级大幅波动现象,证实了特殊限制谱等导致的超低量级和信号干扰是导致大幅波动的两种直接原因。在确定直接原因的基础上分析了该现象的根本原因,据此提出了解决措施,并对措施进行了验证。结果表明解决措施有效,提高控制自由度和采用输出保持均能有效避免大幅波动情况。该问题的解决有助于提高振动试验控制的稳定性和安全性。

鄂尔多斯盆地东缘深部煤层气开发先导试验效果与启示

鄂尔多斯盆地东缘大宁-吉县区块深部煤层气勘探开发取得突破对煤层气产业带来重大影响,引起业内广泛关注和跟进。前期一些学者对深部煤层气勘探开发理论技术难点与对策开展了研究,但缺乏对典型气田开发先导试验系统总结。通过深入剖析深部煤层气地质特征与效益开发难点,总结大宁-吉县区块开发先导试验项目取得的进展和成效,明确开发规律并提出效益开发对策。结果表明:(1)深部煤层具有广覆式发育、含气性好、游离气含量高、保存条件好、煤体结构好、脆性指数高、顶底板封盖性强等地质特征,但微构造发育、渗透性极差、矿化度高等因素制约了深部煤层气效益开发;(2)不同地质条件下气井生产特征差异较大,通过先导试验落实气井产能和适应性开发技术对策,采用滚动开发模式可有效降低煤层强非均质性带来的开发风险;(3)开展地质-工程一体化井网优化设计,构建井网与缝网高度弥合的人造气藏,可实现资源动用和采收率最大化;(4)“长水平段+多段多簇+大砂量”的大规模、大排量极限体积压裂技术可增大有效改造体积和井控储量,大幅提高单井产量;(5)深部煤层气井具有“见气时间短、上产速度快、初期产量高、递减快”的生产特征,可实现短期快速规模上产,但气田长期稳产需持续新井投入;(6)前期开发成本偏高,实现效益开发需不断提高工程作业效率、降低开发成本。综合认为,深部煤层气资源品质好,可动用性强,具备快速推广复制条件,大宁-吉县区块深部煤层气开发实践可为国内其他区块深部煤层气规模动用提供技术借鉴,对加快深部煤层气规模勘探开发具有重要意义。

15种医院口腔抑菌制剂微生物限度检查方法的建立

目的建立15种医院口腔抑菌制剂的微生物限度检查方法。方法以醋酸氯己定口崩片、醋酸氯己定洗剂、复方替硝唑溶液、碘甘油、甲醛甲酚涂剂、硼酸甘油涂剂、人工唾液、脱敏糊剂、干髓糊剂、锌麝酚醛糊剂、牙周塞糊剂、甲硝唑膜、复方克林霉素膜、多聚甲醛新失活剂、多聚甲醛牙髓失活剂为样品(制剂1-15),按2020年版《中国药典(四部)》通则1105,1106,1107项下方法,采用平皿法、薄膜过滤法和培养基稀释法,对5种常见菌(金黄色葡萄球菌、铜绿假单胞菌、枯草芽孢杆菌、白色念珠菌和黑曲霉)进行回收试验,并进行控制菌(金黄色葡萄球菌、铜绿假单胞菌和大肠埃希菌)检查方法适用性试验。结果制剂1-5、9-11、14-15需氧菌总数检查均采用薄膜过滤法,其余制剂均采用平皿法;制剂1-3、6-8、12-13霉菌和酵母菌检查均采用平皿法,其余制剂均采用薄膜过滤法,试验菌回收比均在0.5~2.0范围内;控制菌检查,制剂1-3、5、9-11、14-15均采用薄膜过滤法,其余制剂均采用培养基稀释法,试验组相应阳性菌均能正常检出。结论所建立的方法适用于此15种医院口腔抑菌制剂的微生物限度检查。

抗生素类药品无菌检查方法研究进展

无菌检查法是无菌药品检查的法定检验方法,其中薄膜过滤法因易操作、风险低和准确度高等优点比直接接种法应用更广泛。无菌药品剂型种类繁多,其中抗生素类药品因品种结构多变、抑菌性强和抗菌谱广等因素,一直以来是建立无菌检查方法的难点。本文就薄膜过滤法中的溶解、过滤、冲洗和培养等4个关键步骤展开讨论,通过对已建立的13类47个品种共61个抗生素药品无菌检查方法的综述,探讨建立无菌检查方法的基本策略,并对无菌检查方法和结果的局限性进行讨论,以期为建立抗生素类无菌药品无菌检查方法及正确认识无菌检查结果提供思路和参考。

火灾下活性粉末混凝土梁斜截面承载性能研究

为探明火灾下活性粉末混凝土(Receative power concrete,RPC)梁斜截面承载性能退化规律,设计制作了六根RPC简支梁试件,开展了恒载下ISO834标准火灾试验,获得了时间-位移曲线、荷载-位移曲线、内部温度变化、裂缝开展、破坏形态、高温爆裂等数据,分析了剪跨比、荷载水平、配箍率、纵筋配筋率对火灾下RPC梁斜截面承载性能的影响规律。结果表明:剪跨比、荷载水平是影响RPC梁斜截面耐火极限的关键因素,剪跨比由2.5增至3.5,荷载水平由0.25增至0.45,RPC梁耐火极限可降低30 min以上;配箍率对RPC梁的斜截面承载力和耐火极限影响显著;纵筋配筋率对RPC梁耐火极限影响甚微。火灾高温、爆裂削弱了RPC梁的斜截面承载性能,爆裂导致内部材料直接受火,加速其力学性能劣化,使梁斜截面承载力降低33.5%以上。该研究可为火灾下RPC梁斜截面承载安全及火灾后加固修复提供参考。

多应力小样本加速寿命试验设计与评估方法

针对目前多应力加速寿命试验需要的组合应力水平多、时间长、费用高的问题,提出一种多应力小样本加速寿命试验设计与评估方法。该方法建立了正常使用应力水平下可靠寿命的单侧置信下限与加速应力水平下的可靠寿命置信限之间的数学关系式,给出了正常使用应力水平下高置信度、高可靠度的可靠寿命单侧置信下限计算公式。文中首先针对工程上最常用的双应力情况,分别建立了无耦合和有耦合的双应力小样本加速寿命试验设计与评估方法,它只需在三个(无耦合)或四个(有耦合)组合应力水平下进行加速寿命试验,即可对产品在正常使用应力水平下高置信度、高可靠度的可靠寿命进行评估。然后针对一般的m种应力情况,建立了基于多应力线性加速模型的小样本加速寿命试验设计与评估方法,它只需在m+1个组合应力水平下进行加速寿命试验,即可求得产品在正常使用应力水平下高置信度、高可靠度的可靠寿命单侧置信下限。该方法计算简单,而且对完全数据、不完全数据以及各种分布均适用。大量工程算例和Monte Carlo模拟验证表明,与传统多应力加速寿命试验方法相比,本文方法不但可以节省大量试样和试验时间,而且理论上更加严谨,精度更高。

三水准地震下隔震结构提离摇摆界限谱模型研究及试验验证

准确评价隔震结构的摇摆响应状态是判断地震作用下隔震支座是否稳定以及结构是否安全的重要基础。根据支座的不同受力变形状态,提出隔震结构的摇摆界限状态,即未提离、提离和摇摆状态,并提出了基于刚体摇摆模型的状态判别方法。通过地震时程分析,讨论了高宽比AR、竖向屈重比α_(v)、水平屈重比α_(h)、竖向周期T_(v)、水平周期T_(h)、系统阻尼比η等参数对隔震结构摇摆响应的影响,得到了隔震结构未提离、提离、摇摆的界限谱以及各参数对界限谱的影响规律,并通过两个振动台试验进行验证。分析结果表明,摇摆响应随α_(v),T_(h),η的增加而减小,随AR,T_(v)增加而增大,其中T_(v),T_(h)对摇摆响应的影响最大,控制摇摆响应最关键的措施是增加T_(h)、减小T_(v)。