999感冒灵新工艺流膏预防性给药对流感病毒感染小鼠的体内药效学试验研究及机理探讨

Pharmacodynamic Experiment and Mechanism Exploration of Antivirus Effect of 999 Ganmaoling Extractum with New Process Before Administration of Influenza Virus in Mice

目的采用甲型H1N1流感病毒感染小鼠肺炎模型,评价999感冒灵新工艺流膏对流感的预防作用,为临床预防流感的应用提供试验依据。方法采用甲型H1N1流感病毒FM1和PR8株分别感染免疫低下动物造成肺炎模型,新工艺大、中、小剂量分别为每天1.8g生药/kg、0.9g生药/kg、0.45g生药/kg(分别相当于人临床用药量的2倍、等倍和1/2倍),原工艺小鼠剂量为每天1.34g生药/kg(相当于人临床用药量的2倍),醇沉沉淀小鼠用量为每天0.48g生药/kg(相当于人临床用药量的2倍),提前预防性给药4天,观察不同工艺999感冒灵流膏对肺指数、死亡率、死亡保护率、平均存活天数和生命延长率的影响,并测定小鼠血清中CD4/CD8比值,进行机理的探索性研究。结果 FM1和PR8株病毒感染免疫低下小鼠造成肺炎模型,提前预防性给予999感冒灵浸膏4天后,FM1株和PR8株新工艺大、中、小剂量组、原工艺组以及醇沉沉淀组肺指数均无明显降低(P>0.05)。对FM1株模型原工艺组可延长动物平均存活天数,(P<0.01);对PR8株模型新工艺大、中剂量组动物的死亡数明显减少(P<0.05),新工艺大剂量组和原工艺组可以延长小鼠存活天数(P<0.05)。新工艺及原工艺对FM1株及PR8株感病毒感染免疫低下小鼠血清中CD4/CD8比值无明显影响。结论 999感冒灵新工艺对FM1和PR8株感染小鼠肺炎均有一定预防作用。

Objective Pneumonia model infected with influenza virus H1N1 was adopted to evaluate the efficacy of in vivo protection of 999 Ganmaoling extractum made by new process. Experimental basis for the prevention of influenza for clinical application was provided. Methods Pneumonia model was set up by infection of the immunocompromised mice with influenza virus FM1 and PR8 of H1N1 Large, moderate, and small doses of the extractum with new process were 1.8g crude drug/kg per day, 0.9g crude drug/kg per day, and 0.45g crude drug/kg per day , which amounted to twice, once, and half dosage in clinic respectively. Dosage of the extractum with old process was 1.34g crude drug/kg per day, which amounted to twice of the dosage in clinic. Dosage of the extractum with alcohol sedimentation technique was 0.48g crude drug/kg per day equivalent to twice dosage in clinic. Different extractum were administered for 4 days before the administra- tion of virus, and then observe thelung index., death rate, protection rate of death, life extension rate and CD4/CD8 in blood serum to explore the mechanism. Results After 4 days of prophylactic administration with 999 Ganmaoling on pneumonia models of immunocompromised mice affected with FMI and PR8, extractum, the lung index of all groups were decreased apparently （P 〉0.05 ）. Average survival days of animal in FM1 ,old process group were prolonged （P 〈 0. O1 ）. Deaths of animal in PR8, large and moderate dosage with new process group were decreased apparently （ P 〈 O. 05 ）, survival days of animal in large dosage with new process and old process were prolonged （ P 〈 0. 05）. CIM/CD8 of animal in FM1 and PR8 has no significant effect by new process and old process group. Conclusion 999 Ganmaoling with new process had preventive effect to pneumonia mice infected with influenza virus FM1 and PR8.