荷胆胶囊主要药效学及表观药动学研究

【作者】 唐思文；

【导师】 王家葵；

【作者基本信息】 成都中医药大学 ， 中药学， 2004， 硕士

【摘要】 荷胆胶囊是治疗急性胆囊炎及慢性胆囊炎急性发作的内服胶囊剂，根据其拟临床功效，利用两种动物实验性胆囊炎模型（大肠杆菌致家兔细菌性胆道感染和林可霉素致豚鼠胆囊炎症），及利胆（大鼠胆管插管法和小鼠胆囊重量法）、抗菌、解热、抗炎、镇痛等试验进行主要药效学评价。结果表明：（1）受试药物100mg/Kg、200mg/Kg、400mg/Kg（分别相当于成人日用量的5、10、20倍）灌胃给药，连续7天，对大肠杆菌致家兔细菌性胆道感染有一定的治疗作用，可降低感染动物发热体温，对抗感染所致外周血白细胞数升高，细菌培养及病理切片证实，给予受试药物后，动物胆囊炎症程度减轻，胆汁中细菌数有所减少，以400mg/Kg剂量组作用明显。（2）能明显减轻林可霉素所致豚鼠胆囊炎症。（3）能显著增加大鼠单位时间内胆汁排泌量，增加小鼠1h内胆汁分泌。（4）有一定的解热、抗炎、镇痛作用。（5）本品体外抑菌作用较弱。 荷胆胶囊表观药动学研究，以利胆实验（小鼠胆囊重量法）为指标，采用药理效应法进行试验，由于小鼠胆汁排泌是一个累加值，为了消除胆囊内原有胆汁对实验结果的影响，故在原药理效应法的基础上进行了方法学改良，采用两次给药的实验方案。其体存药量的表观药动学过程符合一室开放模型，表观药动学参数为：A：179.326965mg/kg。Ke：0.014179 min^-1，Ka：0.057639 min^-1，Lag time：17.236338min，t_1/2（Ka）：12.025690min，t_1/2（Ke）：48.885319min，T（peak）：49.505959min，C（max）；85.566872mg/kg，AUC：9536.108400（mg/kg）*min，CL/F（s）：0.010486mg/kg/min/（mg/kg），V/F（c）：0.739574（mg/kg）/（mg/kg）。更多还原

【Abstract】 HeDan-capsule is taken orally to cure acute cholecystitisa and chronic cholecystitisa by acute outbreak. According to clinic efficacy, evaluating pharmacodynamics by using following experiments, for example using two kinds of experimental animal’s gallbladder matrix(making coney’s gallbladder channel infected by coliform and making Cavia cobaya cholecystitis by lincomycin),and cholagogue(the method of intubating big rat’s bile duct and weighing albino rat gallbladder) antibacterial antifebrile antiinflammation abirritation etc. The results suggesting: (l)100mg/kg 200mg/Kg 400mg/Kg feeding coney by lavaging stomach, successive 7 days, the drug can ameliorat and cure coney its gallbladder channel infected by lincomycin; lowering temperature of infected pyretic animals, lowering the quantity of outer white blood cell which is enhanced by antiinfecton. Bacteria culturing and pathological section of tissue testing, after given drug, the inflammation of gallbladder can be reduced, the dosage of 400mg/Kg is the most obvious; (2) It can obviously reduce the Cavia cobaya cholecystitis aroused by lincomycin; (3) it can enhance the amount of draining bile by unit time, adding to bile secretion in a hour; (4) it has some antifebrile antiinflammation abirritation;(5)it has weak function of inhibiting outer bacteria.HeDan-capsule apparent pharmacokinetics research, making the target of cholagogue experiment(weighing albino rat gallbladder),doing pharmacology effect’s experiment, The bile secretion of albino rat is one of adding numerical value, in order to eliminating the effect of test result by original bile in gallbladder, we improve the method based on original pharmacological effect, using the plan of given drug twice, its apparent pharmacokinetics process of storing in body accord to one unit matrix, apparent pharmacokinetics parameter: A: 179.326965mg/kg Ke: 0.014179 min-1, Ka: 0.057639 min-1, Lag time: 17.236338min, t1/2(Ka): 12.025690min, t1/2(Ke): 48.885319min, T(peak): 49.505959min, C(max): 85.566872mg/kg, AUC: 9536.108400(mg/kg)*min, CL/F(s): 0.010486mg/kg/min/(mg/kg), V/F(c): 0.739574(mg/kg)/(mg/kg)更多还原