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.     

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。     

参麦注射液质量影响因素的研究进展

参麦注射液是由红参、麦冬制得的中药注射剂,具有益气固脱、养阴生津、生脉的功效,临床上用于治疗气阴两虚型之休克、冠心病、病毒性心肌炎、慢性肺心病、粒细胞减少症。主要围绕与产品质量紧密相关的生产工艺、药材质量、辅料3个方面进行总结,为优化该产品的生产工艺、提高产品质量提供参考。     

银杏酮酯滴丸联合阿加曲班注射液治疗急性脑梗死的临床研究

目的研究银杏酮酯滴丸联合阿加曲班注射液治疗急性脑梗死的临床疗效。方法选取2017年8月-2019年8月安阳市第六人民医院收治的106例急性脑梗死患者为研究对象,所有患者随机分为对照组和治疗组,每组各53例。对照组患者静脉注射阿加曲班注射液,20 mg阿加曲班注射液溶于250 mL生理盐水中,1次/d;治疗组在对照组基础上口服银杏酮酯滴丸,8丸/次,3次/d。两组患者持续治疗14d。观察两组的临床疗效,NIHSS评分、BI指数评分和m RS评分及高敏C反应蛋白(hs-CRP)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、血栓素A2(TXA2)、内皮素-1(ET-1)和一氧化氮(NO)水平。结果治疗后,对照组和治疗组的总有效率分别为81.13%、96.23%,两组比较差异有统计学意义(P<0.05)。治疗后,两组NIHSS评分和m RS评分明显下降,BI指数评分明显升高(P<0.05),且治疗组各评分改善较多(P<0.05)。治疗后,两组hs-CRP、IL-6、TNF-α水平显著降低(P<0.05);并且治疗组hs-CRP、IL-6、TNF-α水平降低较多(P<0.05)。治疗后,两组血清TXA2、ET-1水平均明显降低,NO水平明显升高(P<0.05),且治疗组TXA2、ET-1、NO水平改善较多(P<0.05)。结论银杏酮酯滴丸联合阿加曲班注射液治疗急性脑梗死具有较好的治疗效果,改善神经功能和日常生活活动能力,调节血清因子水平,安全性较高,值得在临床上推广应用。     

Comparison of Protective Effects of Safflor Injection and Extract of Ginkgo Biloba on Lung Ischemia/Reperfusion Injury in Rabbits

Objective:To observe the protective effects of safflor Injection(SI) and extract of Ginkgo biloba(EGB) on lung ischemia-reperfusion injury(LIRI) and investigate its mechanism.Methods:In vivo rabbit model of LIRI was reconstructed.Forty rabbits were randomly and equally divided into four groups:sham-operation group(sham group),ischemia-reperfusion group(model group),ischemia-reperfusion plus SI group(safflor group) and ischemia-reperfusion plus EGB injection group(EGB group).Malondialdehyde(MDA) content,superoxide dismutase(SOD) and xanthine oxidase(XO) activity in serum were measured.The wet/dry weight ratio(W/D) of the lung tissue and activity of myeloperoxidase(MPO) were also tested.Ultrastructure change of the lung tissue was observed by the electron microscope.The expression of intercellular adhesion molecule-1(ICAM-1) was measured by immunohistochemistry(IHC).Results:In the model group,MDA and XO increased and SOD decreased in serum compared with the sham group(P<0.01).The values of W/D,MPO and ICAM-1 of the model group were higher than those of the sham group(P<0.01),but those of the safflor group and EGB group were significantly lower than those of the model group(P<0.01).The IHC demonstrated that ICAM-1 expression in lung tissue of the model group was significantly higher than those of the safflor group(P<0.01).Compared with safflor group,in the EGB group MDA,XO,MPO decreased,SOD and ICAM-1expression increased(P<0.05),but the change of W/D was not statistically significant(P>0.05).Conclusions:SI and EGB may attenuate LIRI through antioxidation,inhibition of neutrophil aggregation and down-regulation of ICAM-1expression.But EGB had more effect on the antioxidation,while SI did better on regulating ICAM-1 expression.     

Bacterial colonization of peripheral intravenous cannulas in a tertiary care hospital: A cross sectional observational study

BackgroundThe use of intravenous (IV) cannulas is an integral part of patient care in hospitals. These intravenous cannulas are a potential route for microorganisms to enter the blood stream resulting in a variety of local or systemic infections. Studies showing the actual prevalence of colonization of peripheral IV cannulas and its role in BSI are lacking. Hence, this study was aimed to estimate the prevalence of colonization of the injection ports of peripheral IV cannulas.MethodsThis cross sectional study was conducted on patients admitted in ICU and wards in an 800 bedded tertiary care hospital. Swabs were taken from lumens of peripheral IV cannulas and cultured. Patient demographic data and practices followed for maintenance of IV line were noted.ResultsA total of 196 injection port samples were taken, out of which 11 tested positive for microbial growth (5.61%). Staphylococcus aureus was the predominant organism contributing 64% of the microbial growth. A significant association was seen between presence of local signs, old age and positive cultures. Flushing IV cannula every 6 h was associated with negative cultures.ConclusionPeripheral IV cannulation has significant potential for microbial contamination and is largely ignored. Most of the risk factors associated with growth of microorganisms in the injection ports of peripheral intravenous cannulas (which has a potential to cause catheter-related blood stream infections) can be prevented by improving protocols for management. To prevent infection from occurring, practitioners should be educated and trained about the care and management of IV.     

康莱特注射液＋胸腺法新＋分子靶向药物联合立体定向放疗治疗脑转移瘤23例

目的评价康莱特注射液＋胸腺法新＋分子靶向药物联合立体定向放疗治疗脑转移瘤的临床疗效。方法将已有明确病理诊断的原发灶癌，经复查头颅CT或磁共振或PET／CT确诊为脑转移瘤的46例患者随机分为治疗组和对照组各23例，其中原发灶癌手术切除术后32例，不能手术或患者拒绝手术14例，每组手术切除术后和没有手术的患者分别为16例、7例。对照组采用全脑放射治疗，治疗组采用立体定向放疗，同时给予康莱特注射液＋胸腺法新（基泰）＋吉非替尼（gefitinib）。结果治疗组总有效率82．61％，对照组为26．09％，二组比较，差异有统计学意义（P〈0．05）。治疗组放疗后头痛症状明显改善，恶心、呕吐反应较轻，KPS评分增加，较对照组比较，差异均有统计学意义（P〈0．05）。结论康莱特注射液＋胸腺法新＋吉非替尼联合立体定向放疗治疗脑转移瘤能明显改善患者的临床症状，降低副作用，提高肿瘤患者的生活质量。