炎痛宁胶囊抗炎作用及一般毒理学评价

发布时间：2018-06-23 00:17

本文选题：炎痛宁胶囊 + 骨关节炎　；参考：《吉林大学》2015年硕士论文

【摘要】：目的根据炎痛宁胶囊处方依据,在肯定临床疗效的基础上,进行该药物抗炎作用及毒理学安全性评价的实验研究,研究该方抗炎镇痛、活血化瘀作用及对大鼠胶原诱导性关节炎(CIA)损伤的治疗作用并进行比格犬长期毒性实验以评价药物安全性。方法采用小鼠醋酸扭体反应、甲醛刺激大鼠足跖试验等动物模型观察炎痛宁胶囊的镇痛作用;采用小鼠巴豆油性耳肿、小鼠腹腔毛细血管通透性、大鼠角叉菜胶足肿、大鼠棉球肉芽肿实验动物模型,观察炎痛宁胶囊的抗炎作用;建立血瘀模型,观察炎痛宁胶囊的活血化瘀作用;建立大鼠CIA模型,观察炎痛宁胶囊对CIA大鼠足肿胀和踝关节局部病理损伤的治疗作用。将炎痛宁胶囊以3种剂量通过口服方法对比格犬进行持续9个月的重复给药,观察药物对动物一般体征、饮食、肛温、体重的影响,同时进行尿液、血液学、血液生化、心电图、眼科等检查,在给药结束和停药恢复后进行大体剖检并进行组织病理学检查以及骨髓检查等,以评价药物的毒性。结果1.炎痛宁胶囊对化学刺激引起的疼痛有明显的镇痛作用,可显著减少甲醛刺激致大鼠Ⅱ相疼痛舔足、抖足、抬足次数,表明炎痛宁胶囊具有明显镇痛作用,对温热刺激引起的疼痛无明显的镇痛作用,其作用机制可能通过外周机制介导。2.炎痛宁胶囊对巴豆油致小鼠耳肿胀模型、角叉菜胶致大鼠足肿试验、毛细血管通透性试验及棉球肉芽肿试验均有明显的抗炎作用,表明炎痛宁胶囊对急性炎症和慢性炎症具有显著的抑制作用。3.炎痛宁胶囊对对侧足的踝关节肿胀有显著的抑制作用,显著改善模型大鼠耳、鼻、尾、爪等部位的继发性病变,表明炎痛宁胶囊对Ⅱ型胶原性关节炎有显著的治疗作用。4.炎痛宁胶囊能够显著减轻滑膜细胞增生,明显减轻滑膜组织充血水肿、血管增生和浸润炎细胞数量、血管翳的形成。5.比格犬口服重复给予炎痛宁0.67、2.0、6.0g生药/kg剂量9个月,各给药组动物与生理对照组比较,一般观察、体重、肛温、血液学、血清生化、尿液生化、心电图检查以及眼科检查等均未见明显药物毒性作用;给药结束及恢复期结束时骨髓检查、大体解剖、脏器重量以及组织病理学检查等也均未见明显药物毒性作用。结论炎痛宁胶囊具有明显的镇痛、抗炎作用,对炎性疼痛作用最好,且呈现一定的量效关系,其镇痛部位在外周;对CIA大鼠有显著地治疗作用,可减轻炎症及组织损伤,减少炎症介质的释放,减轻局部炎症,改善关节肿胀,对减轻组织损伤,修复骨质破坏,对恢复机体生理功能有积极意义。并且由比格犬9个月长期毒性试验可以检测该药物对动物一般观察、饮食观察、体重、肛温、心电图、尿液、血液学、血液生化、尿液生化、大体解剖学、组织病理学的影响,从而评价了药物的安全性。结果表明,炎痛宁胶囊有显著的活血化瘀、抗炎镇痛的作用,同时纯中药制剂避免了动物注射或口服甾体或非甾体抗炎药后消化系统、内分泌系统及骨关节系统的强烈毒性作用。炎痛宁胶囊补肝肾、祛风湿,活血通络充分发挥扶正固本的作用,与其标本兼治的治则一致。本研究为推广和探索骨关节炎治疗的新途径、创新新的治疗骨关节炎新药提供思路和方法。
[Abstract]:Objective according to the prescription of Yan Tong Ning capsule prescription, on the basis of affirming the clinical curative effect, the experimental study on the anti inflammatory effect and toxicological safety evaluation of the drug was carried out to study the anti inflammatory and analgesic effect of the prescription, the effect of activating blood circulation and removing stasis and treating the injury of collagen induced arthritis (CIA) in rats and to evaluate the long-term toxicity test of the Beagle dog to evaluate the drug. Methods the analgesic effect of Yantongning capsule was observed in mice with acetic acid torsional reaction, formaldehyde stimulated rat foot test and other animal models to observe the analgesic effect of Yantongning capsule. The anti inflammatory effects of Yantongning capsule were observed by the experimental animal models of mice with oil induced ear swelling, mouse peritoneal capillary permeability, rat carrageenan foot swelling and rat cotton pellet granuloma. To establish a blood stasis model and observe the effect of activating blood and removing blood stasis in Yan Tong Ning capsule, the rat CIA model was established to observe the effect of Yan Tong Ning Capsule on the foot swelling and the local pathological injury of the ankle joint in CIA rats. The repeated administration of Yan Tong Ning Capsule on the Beagle dog by oral method was carried out by oral method at 3 doses, and the drug general body was observed. Symptoms, diet, anus temperature, weight, urine, hematology, blood biochemistry, electrocardiogram, ophthalmology, general examination, histopathological examination and bone marrow examination after the end of the administration and the recovery of the drug, in order to evaluate the toxicity of the drug. The pain of the 1. inflammatory drugs is obvious in the town. The analgesic effect can significantly reduce the pain and licking of the rats, the foot and the number of feet, and the times of lifting the foot. It shows that the analgesic effect of Yantongning capsule has obvious analgesic effect and has no obvious analgesic effect on the pain caused by warm irritation. The mechanism of its action may be mediated by the peripheral mechanism of.2. Yongning capsule to the mouse ear swelling model induced by bean oil, carrageenan The rat foot swelling test, capillary permeability test and cotton ball granuloma test have obvious anti-inflammatory effects. It shows that Yan Tong Ning capsule has a significant inhibitory effect on acute inflammation and chronic inflammation..3. Yongning capsule has a significant inhibitory effect on the swelling of the ankle joint of the side foot, and significantly improves the model rats' ears, nose, tail, and paws. The secondary pathological changes showed that Yan Tong Ning capsule has a significant therapeutic effect on type II collagen arthritis..4. Yan Ning capsule can significantly reduce the proliferation of synovial cells, reduce the hyperemia and edema of the synovial tissue, the number of vascular hyperplasia and infiltrating inflammatory cells, and the formation of pannus,.5., is repeated to the 0.67,2.0,6.0g biogenic drug of yagenning. The dose of /kg was 9 months. There were no obvious toxic effects on the body weight, anus temperature, hematology, serum biochemistry, urine biochemistry, electrocardiogram and Ophthalmology, and the end of the drug and the bone marrow examination, gross anatomy, organ weight, histopathology, etc. Conclusion Yan Tong Ning capsule has obvious analgesic and anti-inflammatory effects and has the best effect on inflammatory pain, and has a certain dose effect relationship. Its analgesic site is in the peripheral area; it has a significant therapeutic effect on CIA rats. It can reduce inflammation and tissue damage, reduce the release of inflammatory mediators, alleviate local inflammation, and improve customs clearance. Swelling, to reduce tissue damage, repair bone destruction, to restore the body's physiological function has positive significance. And by 9 months of the Beagle Dog long-term toxicity test can detect the drug on animal general observation, diet observation, weight, anus temperature, electrocardiogram, urine, hematology, blood biochemistry, urine biochemistry, gross anatomy, histopathology The results show that the capsule has significant effects of activating blood circulation and removing blood stasis, anti-inflammatory and analgesic effect. At the same time, the pure Chinese medicine preparation avoids the digestive system, the endocrine system and the bone and joint system of the animals after the injection or oral steroid or non steroidal anti-inflammatory drugs. This study is a new way to promote and explore the new treatment of osteoarthritis and to provide new ideas and methods for the new drugs for the treatment of osteoarthritis.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：S853.7

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