溴芬酸钠滴眼液抑菌效力研究

目的对溴芬酸钠滴眼液中所添加的抑菌剂抑菌效力进行确认。方法将金黄色葡萄球菌、大肠埃希菌、铜绿假单胞菌、白色念珠菌和黑曲霉作为挑战菌株,分别加入到抑菌剂含量为处方浓度0、80%、100%和120%的4组溴芬酸钠滴眼液中,在不同时间段检测样品中微生物的存活情况。结果不含抑菌剂的溴芬酸钠滴眼液不具有充分的抗菌活性,抑菌剂含量为处方浓度80%、100%和120%的溴芬酸钠滴眼液,均可有效抑制微生物的生长繁殖。结论可选择浓度为0.05mg/m L的苯扎氯铵,作为溴芬酸钠滴眼液的抑菌剂。     

枸橼酸钾溶液中抑菌剂的抑菌效果观察

目的 考察枸橼酸钾溶液中抑菌剂的抑菌效果.方法 以《中国药典》中规定的5种常规菌株金黄色葡萄球菌、大肠埃希菌、铜绿假单胞菌、白色念珠菌和黑曲霉作为挑战菌,4组枸橼酸钾溶液分别加入含量为处方浓度0、80%、100%、120%的抑菌剂羟苯乙酯醇溶液,在刚生产时和刚过有效期时对样品进行抑菌活性试验,探讨其在6个月有效期内的抑菌剂有效性.结果 枸橼酸钾溶液中羟苯乙酯醇溶液的处方量10%(mL/100 mL)时,对5种常规菌株的抑菌效力均符合药典规定.结论 枸橼酸钾溶液中羟苯乙酯醇溶液现有处方浓度是可行的,而且在有效期内均能达到抑菌效果.     

HPLC法测定乙酰半胱氨酸口腔崩解片的含量及其有关物质

目的建立乙酰半胱氨酸口腔崩解片含量及其有关物质的测定方法。方法采用高效液相色谱法,色谱柱VP-ODS(150 mm×4.6 mm);流动相0.68%磷酸二氢钾溶液(pH3.0);检测波长214 nm;流速1.3 m l.m in-1。结果乙酰半胱氨酸浓度在159.2~796.0 mg.L-1的范围内,其峰面积与浓度呈良好线性关系,回归方程S=17083.C 175257,r=0.999 8;乙酰半胱氨酸最低检测限为2.9×10-3μg;平均回收率为99.8%(n=15)。结论该方法方便简便、准确、可靠,适于产品的质量控制     

人干扰素α1b喷雾剂抑菌剂筛选及抑菌效力研究

目的:探索人干扰素α1b喷雾剂制剂处方中抑菌剂及其最低有效抑菌浓度,确定抑菌剂的合理添加剂量。方法:应用生物学活性检测方法进行人干扰素α1b喷雾剂制剂处方中抑菌剂的筛选,确定抑菌剂,然后按照2020年版《中华人民共和国药典》通则1121抑菌效力检查法测定抑菌效力确定抑菌剂的最低有效抑菌浓度。以金黄色葡萄球菌、铜绿假单胞菌、白色念珠菌和黑曲霉为试验菌株,进行菌落计数方法适用性试验。设计抑菌剂剂量筛选试验,对不同浓度的抑菌剂分别对4种试验菌的抑菌效果进行考察,筛选出抑菌剂的合理添加量。结果:筛选出人干扰素α1b喷雾剂制剂处方中的抑菌剂为苯扎溴铵;苯扎溴铵浓度为0.05～0.1 mg·mL^-1时对金黄色葡萄球菌、铜绿假单胞菌、白色念珠菌和黑曲霉的抑菌效力均符合A级。结论:确定了人干扰素α1b喷雾剂制剂处方中抑菌剂苯扎溴铵的最低有效抑菌浓度为0.05 mg·mL^-1。     

乙酰半胱氨酸口服溶液的制备与质量控制

目的制备乙酰半胱氨酸口服溶液并建立其质量控制方法。方法以乙酰半胱氨酸为主药，采用溶剂煮沸、充氮气保护等措施制备口服溶液，采用高效液相色谱法测定乙酰半胱氨酸含量，并进行方法学验证和初步稳定性考察。结果制得的口服溶液澄清透明，味甜，气清香，质量稳定；建立的含量测定方法，浓度在0.1～2.0 mg•mL－1范围内与峰面积呈良好线性关系，回归方程为A＝－50 714.33+7.21×106×C，r＝0.999 5；精密度实验RSD＝0.922%（n＝5）；平均回收率99.32%，RSD＝0.826%（n＝5）。结论该口服溶液处方组成、制备工艺、质量控制方法科学、合理，适用于该产品工业化生产和质量控制。     

过甲酸氧化柱前衍生HPLC法测定复方氨基酸注射液(18AA-Ⅴ)中盐酸半胱氨酸含量

目的 建立柱前衍生高效液相色谱法测定复方氨基酸注射液(18AA-Ⅴ)中盐酸半胱氨酸含量的方法,完善质量标准.方法 盐酸半胱氨酸被过甲酸氧化后,用6-氨基喹啉-N-羟基琥珀酰亚胺基氨基甲酸酯(AQC)衍生化,采用Kromasil C18(250mm×4.6mm,5μm)色谱柱,以140mmol·L-1醋酸铵缓冲液(pH 5.00)和乙腈-水(60:40)溶液为流动相进行梯度洗脱,检测波长为248nm,进样量5μL.结果 盐酸半胱氨酸在1.78~7.11μg·mL-1范围内浓度与峰面积线性相关,相关系数为0.9995;在标示浓度的80%、100%、120%三个浓度水平的平均回收率为97.5%,RSD为2.7%(n=9).结论 本法操作简便,具有较好的灵敏度与重现性.     

高效液相色谱法测定复方替硝唑凝胶中3组分

目的:采用高效液相色谱法同时测定复方替硝唑凝胶中替硝唑、水杨酸和氯霉素的含量.方法:色谱条件:ODSC18分析柱,流动相为甲醇-0.04 mol·L-1磷酸二氢钾溶液-乙腈(30:55:15),检测波长300nm.结果:替硝唑、水杨酸和氯霉素的线性范围分别为:4.0～79.2 mg·L-1,3.0～60.4 mg·L-1,2.4～47.6 mg·L;替硝唑、水杨酸和氯霉素的平均回收率分别为120%,100%,80%;3种浓度的回收率分别为:99.6%RSD%为1.15,99.7%RSD%为1.88,99.9%RSD%为0.88.日内、日间精密度RSD均小于5%.结论:高效液相色谱法用于复方替硝唑凝胶的含量测定,方法简单,专属性强.     

乙酰半胱氨酸胶囊的处方筛选及含量测定

目的对乙酰半胱氨酸胶囊的处方进行筛选,制备乙酰半胱氨酸胶囊,测定其含量。方法对乙酰半胱氨酸胶囊的处方进行筛选,高效液相色谱法测定含量,流动相:0.68%磷酸氢二钾溶液(用磷酸调节pH值至3.0)-甲醇=95∶5;检测波长为214 nm,进样量:10μL。结果乙酰半胱氨酸200 g、微晶纤维素50 g,0.5%羟丙基甲基纤维素(75%乙醇溶)为最佳处方。乙酰半胱氨酸在0.1274⁰.4248 mg/mL之间呈良好的线性关系(r=0.9996,n=5),平均回收率为99.53%,RSD%为1.60%(n=9)。结论该制剂制备工艺合理可行,含量测定方法准确可靠。     

HPLC法测定加替沙星滴眼液中抑菌剂羟苯乙酯的含量

目的建立HPLC法测定加替沙星滴眼液中抑菌剂羟苯乙酯的含量。方法采用Agilent Zorbax SB C18色谱柱;流动相为0.005 m ol.L-1醋酸胺溶液(每1 000 m l中含三乙胺10 m l,冰醋酸调节pH值至5.0)-乙腈(60∶40);流速:1.0 m l·m in-1;检测波长:256 nm;柱温:35℃。结果羟苯乙酯在3.06~30.55 mg·L-1范围内与色谱峰面积呈良好的线性关系(r=0.999 9),平均加样回收率为100.38%,RSD为0.7%(n=9)。结论该方法简便、准确、重复性好,适用于检测加替沙星滴眼液中抑菌剂羟苯乙酯的含量测定。     

颌面血管瘤局部注射用平阳霉素脂质体的制备和优化

目的制备平阳霉素脂质体,建立包封率测定方法,考察处方影响因素,优化处方。方法采用硫酸铵梯度法制备平阳霉素脂质体;以Sephadex G-50微柱离心法分离脂质体和游离药物,应用HPLC法测定药物含量,计算包封率;通过单因素考察优化硫酸铵梯度法的处方工艺,考察不同处方因素对包封率的影响。结果 Sephadex G-50微柱可完全吸附平阳霉素游离药物,空白脂质体回收率为98.3%~101.2%;平阳霉素浓度在5~200μg·m L-1内与峰面积线性关系良好(r=0.9999),日内和日间精密度(RSD)均<2%,回收率为98.3%~100.1%。通过单因素考察优化平阳霉素脂质体的处方为:磷脂100 mg;胆固醇20 mg;平阳霉素15 mg。优化工艺为采用浓度为250 mmol·L-1硫酸铵溶液制备空白脂质体,加入平阳霉素溶液后在40℃水浴中载药40 min。结论硫酸铵梯度法适用于制备平阳霉素脂质体,微柱离心法测定包封率准确可靠,处方工艺优化后的平阳霉素脂质体的包封率可以达到63.7%。     

New antimicrobial agents

This section covered one of the most eagerly awaited topics during this year's ICAAC meeting, the discovery of new agents against bacterial, fungal and viral disease. Compounds such as Microcide Pharmaceuticals Inc's MC-02479, Wyeth-Ayerst Research's GAR-936 and Bayer AG's Bay-38-4766, were presented. These presentations were mainly in the form of posters and were all very well attended.     

New antimicrobial frontiers

New antimicrobials able to counteract bacterial resistance are needed to maintain the control of infectious diseases. The last 40 years have seen the systematic tailoring and refinement of previously identified antibiotics, to produce a multitude of semi-synthetic derivatives that share their mechanism of action with the original molecules. The major limit of this approach is the emergence of multi- and cross-resistant bacterial strains, favoured by the selective pressure inherent to the targeting of specific enzymes. The most promising new strategies aim to the development of molecules that, targeting essential bacterial structures instead of specific enzymatic activities, achieve infection control without enforcing a selective pressure on bacteria. This review, based on the consultation of the up-to-date literature, deals with antimicrobial peptides and some antivirulence factors.     

Tackling antimicrobial resistance

Bacteria resistant to antibiotic therapy are becoming much more common and this has led to mounting concern in the UK and worldwide. Many pathogens are now 'multiresistant', that is, they are resistant to several classes of antimicrobial drug. Infection with such organisms may be particularly difficult to treat. In this article, we briefly discuss how resistance and multiresistance occur. We consider some of the important pathogens involved and the problems they pose in hospitals and the community. We discuss strategies for slowing the accumulation of antibiotic resistance and the implications for doctors treating patients with common infections.     

Optimizing antimicrobial prescribing

Antibiotics are universally prescribed drugs. Because they exert selective pressure and because of the innate bacterial ability for adaptation, even the appropriate clinical use of these potentially life-preserving agents inevitably fosters the development and spread of resistance by a variety of microorganisms. Inappropriate use has accelerated and increased the magnitude of a problem that is now considered a public health crisis. For Gram-positive pathogens some compounds offer limited hope, but for Gram-negative organisms no new drugs with radically increased spectra are available for clinical trials. Patients with serious infections due to multiresistant organisms are experiencing adverse, sometimes fatal, clinical outcomes. Use of multiple drugs increases side effects and exposes additional susceptible bacteria to selective pressure. There is evidence that the appropriate use of currently available antibiotics can be associated with a reduction of the spread of resistance. Antibiotic stewardship programmes and the antibiotic 'care bundle' approach can be effective measures to lengthen the useful life of antibiotics and can be implemented in most clinical situations.     

肺炎克雷伯菌耐药率变迁与抗菌药物使用强度的相关性分析

目的：探讨医院肺炎克雷伯菌耐药率与常用抗菌药物使用强度（antibacterial use density,AUD）的相关性,为临床合理使用抗菌药物治疗肺炎克雷伯菌感染提供参考依据。方法：统计收集2012-2017年度医院住院病区常用抗菌药物AUD,监测肺炎克雷伯菌的临床分布和对常见抗菌药物耐药率的变化趋势,采用Pearson相关方法分析其耐药率与抗菌药物AUD的相关性。结果：2012-2017年肺炎克雷伯菌对亚胺培南和美罗培南等多种抗菌药物的耐药率呈现明显变化趋势（P<0.01）,其中对哌拉西林他唑巴坦、头孢西丁、亚胺培南、美罗培南、阿米卡星的耐药率均小于30%,但对哌拉西林、氨苄西林舒巴坦、头孢唑林、复方磺胺甲噁唑的耐药率均大于50%。肺炎克雷伯菌对哌拉西林耐药率与头孢他啶AUD呈显著正相关（P<0.01）;对头孢吡肟耐药率与头孢呋辛AUD呈负相关（P<0.05）;对亚胺培南耐药率与阿莫西林克拉维酸钾AUD呈正相关（P<0.05）,与头孢唑林AUD和环丙沙星AUD呈负相关（P<0.05）;对环丙沙星耐药率与庆大霉素AUD呈负相关（P<0.05）;对庆大霉素、妥布霉素和复方磺胺甲噁唑耐药率与哌拉西林AUD均呈正相关（P<0.05）。结论：哌拉西林他唑巴坦、头孢西丁、亚胺培南、美罗培南和阿米卡星仍然可以作为临床经验治疗肺炎克雷伯菌感染的首选用药,哌拉西林、氨苄西林舒巴坦、头孢唑林和复方磺胺甲噁唑则需要参照药敏试验结果进行选药。肺炎克雷伯菌耐药率变化与抗菌药物AUD密切相关,临床需要加强对抗菌药物合理使用的管控,以降低抗菌药物使用强度,以减少细菌耐药性的产生。     

抗菌药物临床应用专项整治活动对医院住院患者抗菌药物使用的影响研究

目的：分析自2010年以来,国家卫计委实施的抗菌药物临床应用专项整治活动对某市医保住院患者抗菌药物使用的趋势变化情况。方法：采用观察和回顾性研究方法,从某省会城市医疗保险信息系统采集数据,应用统计描述和单因素分析方法分析2010-2014年间医院住院患者抗菌药物使用情况。结果：2010-2014年间住院患者抗菌药物的使用率呈逐年下降趋势,从2010年的65.1%下降到2014年的43.5%;3种及以上抗菌药物联合用药率也呈下降趋势,从2010年的38.6%下降至2014年的24.2%;细菌培养率则呈上升趋势,从2010年的27.4%增加到2014年的36.6%。住院患者人均抗菌药物费用呈现逐年下降趋势,从2010年的1 125.8元下降至2014年612.33元。结论：2010-2014年间,国家卫计委通过实施抗菌药物临床应用专项整治活动,抗菌药物的使用逐渐趋于合理。     

Palladacycles as antimicrobial agents

This review article deals with the structure activity relationship (SAR) for a variety of palladacycles in biomedical applications. Moreover, the types of antibacterial, antifungal, antimycobacterial and antiprotozoal (antiamoebic and antitrypanosomal) activities will vary considerably from one country to another. Therefore, all efforts will be required to face such a vast diversity of problems. This study gives an up to date overview of the antibacterial, antifungal, antimycobacterial and antiprotozoal chemistry of the palladium group elements with an emphasis on the new strategies used in the development of new antibacterial agents. Methodologies for application of bulky aromatic or aliphatic nitrogen ligands, chiral organic moieties, chelates containing other donor atoms than nitrogen, and biologically active ligands in the design of agents analogous to palladacycles are presented. Therefore, the use of palladacycles in medicinal chemistry is interesting as potential application in the biological properties with less toxic drugs compounds..