Repurposing of parenterally administered active substances used to treat pain both systemically and locally

Pain is a constant in our lives. The efficacy of drug therapy administered by the parenteral route is often limited either by the physicochemical characteristics of the drug itself or its adsorption–distribution–metabolism–excretion (ADME) mechanisms. One promising alternative is the design of innovative drug delivery systems that can improve the pharmacokinetics |(PK) and/or reduce the toxicity of traditionally used drugs. In this review, we discuss several products that have been approved by the main regulatory agencies (i.e., nano- and microsystems, implants, and oil-based solutions), highlighting the newest technologies that govern both locally and systemically the delivery of drugs. Finally, we also discuss the risk assessment of the scale-up process required, given the impact that this approach could have on drug manufacturing.Teaser: The management of pain by way of the parenteral route can be improved using complex drug delivery systems (e.g., micro- and nanosystems) which require high-level assessment and shorten the regulatory pathway.     

Matrine,oxymatrine, and compound Kushen injection from the roots of Sophora flavescens: an overview of their anticancer activities

In the present review, we updated current information on the chemistry, contents, and anticancer properties of matrine (MT), oxymatrine (OMT), and compound Kushen injection (CKI). The anticancer properties were focused on lung, breast, and liver cancer cells because they are most susceptible. Sources of information were from Google, Google Scholar, PubMed, PubMed Central, Science Direct, PubChem, J-Stage, Directory of Open Access Journals (DOAJ), and China National Knowledge Infrastructure (CNKI). Reference was also made on botanical websites, such as Flora of China and World Flora Online. MT and OMT are dominant quinolizidine alkaloids from the roots of Sophora flavescens (Kushen) of the family Fabaceae. Against lung, breast, and liver cancer cells, MT and OMT inhibit cell proliferation; induce cell cycle arrest, apoptosis, and autophagy; restrict angiogenesis; and inhibit cell metastasis, invasion, and migration. The processes involve various molecular targets and signaling pathways. CKI is a traditional Chinese medicine (TCM) composed of root extracts of S. flavescens and Smilax glabra (Baituling) of the family Smilacaceae. With MT and OMT as major components, CKI has been approved for the treatment of cancer in China more than 20 years ago. In recent years, systematic reviews and meta-analysis have been undertaken to evaluate the anticancer effects of CKI. When CKI is used alone and in combination with chemotherapy of western medicine, there is much to be learned concerning their interactions besides their individual and integrated efficacy. Some perspectives of MT, OMT, and CKI are discussed, and their suggestions for future research are provided.     

基于网络药理学和分子对接法探索复方一枝蒿颗粒治疗新型冠状病毒肺炎的潜在分子机制

目的 通过网络药理学及分子对接技术探寻复方一枝蒿颗粒治疗新型冠状病毒肺炎的作用机制。方法 应用TCMSP数据库、BATMAN-TCM数据库及文献收集复方一枝蒿颗粒活性成分及潜在靶点。通过TTD、GeneCards和OMMI数据库检索新型冠状病毒肺炎相关的靶点。将复方一枝蒿颗粒药物靶点和新型冠状病毒肺炎相关基因取交集，使用String数据库构建靶蛋白相互作用（PPI）网络。通过Cytoscape构建“药物–活性成分–靶点基因–疾病”网络。对交集靶点进行GO功能、KEGG通路富集分析。利用Autodock_vina软件对活性成分和靶点进行分子对接。结果 共筛选92个活性成分，1 627个靶点，新型冠状病毒肺炎疾病靶点464个，两者取交集筛选出87个潜在靶点。GO功能富集得到2 040个条目（P＜0.05），与病毒过程、参与共生相互作用的生物过程、活性氧代谢过程的调节、与宿主相互作用的生物过程、病毒生命周期、炎症反应的调节等生物学过程有关。KEGG通路分析共得到150条通路，与新冠肺炎密切相关的有人巨细胞病毒感染、结核、COVID-19、IL-17信号通路等。分子对接结果证实，筛选的靶点受体蛋白与活性成分可以较好地结合。结论 复方一枝蒿颗粒可通过多组分、多靶点和多途径的方式对新型冠状病毒肺炎产生治疗作用。     

消癌平注射液联合化疗治疗晚期非小细胞肺癌的Meta分析

[目的]本研究旨在从循证医学角度系统评价消癌平注射液联合化疗治疗晚期非小细胞肺癌（NSCLC）的临床疗效及不良反应。[方法]计算机检索截止至2018年5月已经发表在Cochrane Library、PubMed、EMBASE、中国期刊全文数据库（CNKI）、万方期刊数据库、维普资讯中文期刊服务平台（VIP）中的文献，纳入消癌平注射液联合化疗治疗NSCLC的临床随机对照试验。对纳入的研究采用"偏倚风险评估工具"进行文献质量评价。提取研究特征、方法和结果的数据，运用Review Manager 5.3软件进行分析，并检验发表偏倚。[结果]共纳入文献26篇，病例1 783例。结果显示，与单纯化疗组相比，消癌平注射液联合化疗能提高治疗的总有效率[RR=1.30，95% CI（1.16，1.46），P<0.000 01]、疾病控制率[RR=1.17，95% CI（1.10，1.23），P<0.000 01）]、生活质量[RR=2.16，95% CI（1.80，2.61），P<0.000 01]，并能减少不良反应的发生。[结论]消癌平注射液能提高晚期NSCLC患者化疗疗效，改善生活质量，减轻不良反应。     

多指标综合加权评分法优选复方夏枯草洗剂提取工艺研究

[目的] 优选复方夏枯草洗剂的提取工艺。[方法] 采用L₉（3⁴）正交设计，以迷迭香酸、丹酚酸B的含量及出膏率的综合评分为指标，考察料液比、提取时间、提取次数对提取效果的影响，优选复方夏枯草洗剂的最佳提取工艺。[结果] 根据综合评分的结果，优选出最佳提取工艺为加8倍水，提取3次，每次0.5 h。[结论] 该工艺准确可靠，可行性好。     

参附注射液对猪创伤性心脏骤停复苏后肾损伤的保护作用研究

目的探讨参附注射液对猪创伤性心脏骤停复苏后肾损伤的保护作用。方法国产健康雄性白猪21头,采用随机数字表法分为假手术组(Sham组,n=5)、创伤性心脏骤停复苏(TCA组,n=9)和参附组(SFI组,n=7)。Sham组只经历气管插管及动静脉置管,不经历放血、复苏等过程。TCA组匀速释放总血容量的40%,然后经电刺激法室颤5 min,心肺复苏5 min后常规液体复苏治疗。SFI组在TCA组基础上于复苏后5 min进行参附注射液的干预。于放血前10 min、复苏后1、3、6、24 h检测血清TNF-α、IL-6、肌酐(Cr)、尿素氮(BUN)水平。复苏后24 h经右侧耳缘静脉注射10%氯化钾液20 mL处死猪,迅速获取肾组织标本,应用原位末端标记法(TNUEL法)检测细胞凋亡情况,免疫组织化学法检测半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)的蛋白表达水平。结果TCA组中有8头猪复苏成功,SFI组和Sham组中所有猪复苏成功。与Sham组比较,TCA组血清Cr水平在复苏后24 h、BUN水平在复苏后1、3、6、24 h均明显增高(均P<0.05),TNF-α、IL-6水平在复苏后3、6、24 h明显增高(均P<0.05),复苏后24 h后肾组织细胞凋亡指数及Caspase-3表达增加(均P<0.05)。与TCA组比较,SFI组BUN水平复苏后3、6 h明显降低(均P<0.05),TNF-α、IL-6水平在复苏后3、6、24 h明显降低(均P<0.05),肾组织细胞凋亡指数和Caspase-3蛋白表达有所降低,但差异无统计学意义(均P>0.05)。结论在猪TCA复苏模型中,早期应用参附注射液能够明显减轻复苏后肾损伤。其机制可能与抑制系统炎症反应、减轻细胞凋亡有关。     

舒胃汤联合复方消化酶胶囊治疗肝胃不和型功能性消化不良临床效果观察

目的:探讨分析舒胃汤联合复方消化酶治疗肝胃不和型功能性消化不良(Functional Dyspepsia,FD)的临床效果。方法:选取2016年2月-2019年2月收治的108例肝胃不和型功能性消化不良患者随机分为观察组和对照组,观察组给予舒胃汤联合复方消化酶胶囊治疗,对照组给予复方消化酶胶囊治疗,比较两组临床疗效,治疗前后中医症状评分、胃功能指标。结果:观察组临床疗效总有效率为94.44%较对照组显著提高(P<0.05),治疗前两组中医症状评分无统计学差异(P>0.05),治疗后两组早饱、上腹灼烧感、餐后饱胀不适、上腹痛评分均显著下降,且治疗后观察组早饱、上腹灼烧感、餐后饱胀不适、上腹痛评分下降更显著(P<0.05),治疗前两组胃功能指标无统计学差异(P>0.05),治疗后两组胃排空、胃动素、胃泌素指标水平均显著提高,且治疗后观察组胃排空、胃动素、胃泌素指标水平改善更显著(P < 0.05),观察组不良反应发生率为5.56%,较对照组显著性降低(P < 0.05)。结论:舒胃汤联合复方消化酶胶囊治疗肝胃不和型功能性消化不良可显著提高临床疗效,改善患者临床症状,促进胃功能提高,降低不良反应发生率,值得应用。