A study on clinical effect of Arbidol combined with adjuvant therapy on COVID-19

This study aims to explore the clinical effect of Arbidol (ARB) combined with adjuvant therapy on patients with coronavirus disease 2019 (COVID-19). The study included 62 patients with COVID-19 admitted to the First Hospital of Jiaxing from January to March 2020, and all patients were divided into the test group and the control group according to whether they received ARB during hospitalization. Various indexes in the two groups before and after treatment were observed and recorded, including fever, cough, hypodynamia, nasal obstruction, nasal discharge, diarrhea, C-reactive protein (CRP), procalcitonin (PCT), blood routine indexes, blood biochemical indexes, time to achieve negative virus nucleic acid, and so on. The fever and cough in the test group were relieved markedly faster than those in the control group (P < .05); there was no obvious difference between the two groups concerning the percentage of patients with abnormal CRP, PCT, blood routine indexes, aspartate aminotransferase, and alanine aminotransferase (P > .05); the time for two consecutive negative nucleic acid tests in the test group were shorter than that in the control group; the hospitalization period of the patients in the test group and control group were (16.5 ± 7.14) days and (18.55 ± 7.52) days, respectively. ARB combined with adjuvant therapy might be able to relieve the fever of COVID-19 sufferers faster and accelerate the cure time to some degree, hence it's recommended for further research clinically.     

阿比多尔双层缓释片的研制及体外释药

目的研制阿比多尔双层缓释片并考察其体外释药特性。方法以两种不同处方作湿法制粒、压制双层片，紫外分光光度法测定阿比多尔的释放度。结果阿比多尔双层缓释片的释药曲线用Higuchi方程或Peppas方程拟合，可维持121、持续释放。结论研制的阿比多尔双层缓释片达到设计要求。     

阿比朵尔治疗流行性感冒的随机、双盲、安慰剂对照、多中心临床研究

目的验证盐酸阿比朵尔在中国自然获得流行性感冒受试者中的临床疗效并观察其安全性和耐受性.方法采用随机、双盲和安慰剂对照的多中心临床试验设计.共入组232人,入组条件为年龄≥18岁,≤65岁;发热≥37.8℃;符合流感疑似病例诊断标准;出现症状后不超过36 h.合格的受试者随机接受盐酸阿比朵尔200mg或安慰剂治疗,每日3次,共5 d.结果疗效分析总体为PPi,即指按规定服用药物并完成所有随访且实验室检查证明为流感病毒感染的病例,试验组59例,对照组66例.两组疾病缓解率经生存分析Logrank检验,试验组缓解率高于对照组.试验组疾病持续时间中位数为72.00h(95%可信区间为66.00～78.00h),对照组疾病持续时间中位数为96.00h(95%可信区间为87.46～104.54 h),两组比较差异有显著性(P=0.0083).试验组症状总分下降值的曲线下面积中位数为780.00(95%可信区间为700.77～859.23),对照组中位数为684.00(95%可信区间为559.81～808.19),两组经Wilcoxon检验差异有显著性(P=0.005).共有232例可用于安全性分析,试验组113例,对照组119例.共有20例不良事件可能与研究药物有关,其中试验组7例(6.19%),对照组13例(10.9%),两组间差异无显著性(P=0.245).不良反应主要为消化系统症状和血清转氨酶升高.结论盐酸阿比朵尔在流感发病后早期使用可以缩短疾病的持续时间,减轻症状的严重程度,而且其安全性和耐受性好,适合在临床推广使用.     

Inhibition of influenza hemagglutinin with the antiviral inhibitor arbidol using a proteomics based approach and mass spectrometry

A proteomics gel electrophoresis based approach has been applied to study the effect of arbidol on the proliferation of influenza virus in vitro through quantitation of hemagglutinin levels. An arbidol concentration of 20 μg/ml was required to achieve a 50% reduction in virus proliferation and hemagglutinin levels. The use of a MALDI mass spectrometry approach to study the binding of arbidol to influenza hemagglutinin revealed it bound solely to residues 104–120 of the HA2 subunit, a region known to contain an arbidol resistance mutation. Parallel molecular docking results revealed that this binding site was favoured in which the arbidol molecule binds in two possible orientations approximately 180° to one another at HA2 residues 118–123. The combined studies support the recognized potential of arbidol as an effective and targeted antiviral agent against the influenza virus.     

盐酸阿比朵尔对大鼠的致畸胎作用

背景与目的盐酸阿比朵尔(Arbidol hydrochloride,Ar)为防治流行性感冒新药,为保证临床用药的安全,观察其对大鼠的致畸作用和胚胎毒性。材料与方法将80只妊娠SD大鼠分为5组,即对照组、Ar100、330、1000mg/(kg.d)剂量组和水杨酸钠阳性药组,每组16只大鼠。各组大鼠均于妊娠6~15d连续灌胃给药,妊娠20d解剖。结果Ar高剂量1000mg/(kg.d)使孕鼠体重增长减慢,孕期体重净增值减少,活胎率降低,胎鼠体重、身长和尾长减小,胎鼠骨化迟缓率增加,与对照组比较差异具有统计学意义(P<0.05,P<0.01);但未见胎鼠外观、内脏和骨骼畸形。Ar低和中剂量[100mg/(kg.d)和330mg/(kg.d)]对孕鼠和胎鼠无明显影响。结论330mg/(kg.d)为孕鼠的安全剂量,1000mg/(kg.d)在引起孕鼠毒性反应时有一定的胚胎毒作用,但无致畸胎作用。     

银翘解毒颗粒联合阿比多尔治疗甲型流感的疗效及对炎症介质的影响

目的探讨银翘解毒颗粒联合阿比多尔片治疗甲型流感的疗效及对炎症介质的影响。方法选取2019年5月—2020年11月在天津市中医药研究院附属医院治疗的96例甲型流感患者,根据用药的差别分成对照组和治疗组,每组各48例。对照组口服盐酸阿比多尔片,0.2 g/次,3次/d;治疗组在对照组基础上口服银翘解毒颗粒,15 g/次,3次/d。两组患者均治疗7 d后。观察两组患者临床疗效,比较治疗前后两组患者临床症状改善时间,血清C反应蛋白(CRP)、白细胞介素-1β(IL-1β)、单核细胞趋化蛋白-1(MCP-1)、血清淀粉样蛋白A(SAA)、肿瘤坏死因子-α(TNF-α)水平。结果经治疗,治疗组的总有效率明显高于对照组(97.92%vs 83.33%,P0.05)。经治疗,治疗组在退热时间、咳嗽消失时间、咽喉疼痛消失时间及病毒转阴时间上均短于对照组(P0.05)。经治疗,两组血清CRP、IL-1β、MCP-1、SAA、TNF-α水平均显著下降(P0.05),且治疗组最明显(P0.05)。结论银翘解毒颗粒联合阿比多尔片治疗甲型流感可有效改善患者临床症状,降低机体炎症介质水平,具有一定的临床推广应用价值。     

RP-HPLC法测犬体内盐酸阿比多尔血药浓度

目的:建立RP-HPLC法测定犬血浆中阿比多尔浓度.方法:血浆样品加入内标安定,经饱和碳酸钠碱化处理并用乙醚提取后浓缩进样;流动相为甲醇-水相(72:28),水相为5 mmol/L十二烷基硫酸钠,加入1.32%三乙胺,用磷酸调pH值为3.0;色谱柱为汉邦科技Lichrospher C8(5 μm,250 mm×4.6 mm ID.),检测波长为318 nm,流速为1.0 ml/min.测定了犬口服单剂量阿比多尔片100mg后的血药浓度-时间过程.结果:标准曲线线性范围为10～5 000 ng/ml(r=0.9994);25,250,1 000,5 000 ng/ml平均绝对回收率分别为92.1%,94.1%,104.3%,112.7%;25,250,1 000,5 000ng/ml日内精密度分别为8.0%,8.0%,8.1%,1.6%;25,250,1 000,5 000 ng/ml日间精密度分别为16.5%,7.2%,8.0%,1.3%;该方法符合生物样品分析要求.结论:本法的样品处理过程简便,重现性好,适合大批量样品的测定,用于阿比多尔犬体内血药浓度测定取得良好结果.     

洛匹那韦/利托那韦与阿比多尔及两者联合用药治疗新型冠状病毒肺炎疗效对比研究

目的 分析比较洛匹那韦/利托那韦和阿比多尔及两者联合用药治疗新型冠状病毒肺炎疗效及药物不良反应情况。方法 回顾性分析2020年2月16日—2月26日由广西各地转入广西壮族自治区人民医院邕武院区的75例普通型新型冠状病毒肺炎患者临床资料,根据其用药史分成洛匹那韦/利托那韦联合阿比多尔治疗组(A组)、洛匹那韦/利托那韦治疗组(B组)和阿比多尔治疗组（C组）,比较三组治疗前一般临床指标,治疗后各组药物的疗效、鼻咽拭子核酸转阴率、肺部病灶吸收率、药物不良反应等情况。结果 三组患者平均年龄（42.68±3.44）岁,入院症状主要表现为发热（88.00%）、咳嗽（84.00%）、咽痛（29.33%）和胸闷痛（17.33%）;三组患者入院时性别、年龄、基础疾病、血常规、肝、肾功能等一般情况比较差异均无统计学意义（P>0.05）,治疗后相比,三组患者发病症状好转率（A组94.28%,B组86.21%,C组90.91%）、肺部病灶吸收率（A组88.57%,B组82.76%,C组72.73%）、鼻咽拭子核酸转阴率（A组48.57%,B组48.28%,C组54.55%）差异无统计学意义（P>0.05）; A组、B组患者出现腹泻、恶心、腹胀等药物不良反应症状率显著高于C组患者（A组88.57%,B组82.76%,C组18.18%）（A组88.57%,B组82.76%,C组36.36%）（A组88.57%,B组82.76%,C组36.36%）（P<0.0167）。结论 洛匹那韦/利托那韦和阿比多尔及两者联合用药三种治疗方案用于治疗新型冠状病毒肺炎均取得良好疗效,但临床上洛匹那韦/利托那韦较阿比多尔出现较多药物不良反应。