小儿复方氨酚烷胺栓实验研究

【作者】 彭旦明；

【导师】 熊玉卿；

【作者基本信息】 江西医学院 ， 药理学， 2001， 硕士

【摘要】 目的：1．栓剂（剂型改革）的解热镇痛、抗病毒作用的研究。2．比较不同的给药途径作用的差异。3．分析其差异的主要原因与药动学间的关系。方法：1．采用细胞培养术进行细胞内抗病毒试验；小鼠流感病毒致肺炎试验；以细菌内毒素致家兔发热，观察了两种给药途径对体温升高的影响；以H⁺引起小鼠毛细血管通透性增高，观察了药物抗炎作用；以HAc引起小鼠扭体，观察药物的镇痛作用；采用热板法，观察药物的镇痛作用。2．采用高效液相色谱法，色谱柱为ODS 100C₁₈柱（5μm，250mm×4mm）流动相为甲醇：水（30：70），流速1.0ml/min，血浆样品用乙腈沉淀蛋白质后直接进样。结果：1．药效学试验表明：小儿复方氨酚烷胺栓对流感病毒甲型鼠肺适应株FM₁感染小鼠有明显的抑制作用，降低肺指数，减轻病变程度，减少动物死亡及延长死亡动物存活时间；对病毒致细胞病变有抑制作用；能抑制细菌内毒素致家兔发热反应；提高热刺激及H⁺致痛反应的痛阈值；对醋酸所致小鼠腹腔炎症伊文思兰渗出量无明显影响。2．药代动力学研究结果表明：氨酚烷胺通过灌胃给药及直肠给药两种途径，其对乙酰氨基酚的血药浓度—时间曲线符合一级吸收一房室开放模型，主要药动学参数如下：灌胃给药、直肠给药T_1/2Ka分别为0.115h^-1和0.08h^-1，T_p分别为0.42h^-1和0.15h^-1，C_max分别为4.69μg/ml和48.6μg/ml，AUC分别为11.26μg/ml·h和38.1μg/ml·h。结论：1．通过氨酚烷胺栓及胶囊的药效学研究，栓剂的解热作用发挥更快维持时间更长，镇痛抗病毒作用相近。2．对乙酰氨基酚血药浓度测定方法简便、灵敏度较高，氨酚烷胺栓较胶囊具有吸收快、达峰时间短的特点。更多还原

【Abstract】 Objective: 1. To study antiviral and antipyretic analgesic actions of Paracetamol and Amantadine Suppositories (PAS) .2. During study of pharmacokinetics of paracetamol, a HPLC for determination of paracetamol in rabbit was developed.Methods: 1. The cell culture was used in extrinsic ar抰iviral experiment; others were mouse influenzal viral preumonia experiment, rabbit bacterial toxin fever experiment, and the anti-inflammatory experiment and analgesic experiment caused by I-JAc, and LD50 dose is 748mg/kg.2.HP1 100 system was adopted with a DAD detector, a ODS 100 C18 column (5 ii m,250mmx4mm), a mobile phase consisted of 70% water and 30% methanol and using a flow rate of 1 .Oml/min. After deproteinized with acetonitrile, (PAS) sample was directly injected.Results: 1. PAS could greatly raise the survive time and rate of mice infected by influenzal virus, and possessed obvious antagonize against influenzal virus, and alleviated the pulmonary pathologic change of mice induced influenzal viral pneumonia, and decreased the lung indexes of influenzal virus A; PAS could greatly shrink rabbit fever induced by bacteria toxin, and raise the pain threshold value caused by heat and H~ stimulus, and has no obvious effect to Evans blue exudates cause by HAc and peritonitis.2.The method have a minimum detection limit of 0.05~tg/ml, after single oral administration of 48mg/kg of Paracetamol capsule and suppository the disposition was conformed to a first order absorption a one- 梒ompartment model. The pharmacokinetic parameters of PAS were as follows: T1/2Ka 0.115h?and 0.08h1, T~ 0.42h1 and 0.15h71, Cmax 4.49pg/ml and 48.6~~tg/ml, AUC 11 .26j.tglmbh and 38.1 pg/mFh respectively.Conclusion: The result shows that a simple sensitive method for HPLC determination of Paracetamol in rabbit was developed, and Paracetamol suppository was absorbed and reached peak-time quickly.更多还原