發(fā)布時(shí)間：2018-06-23 00:17

  本文選題：炎痛寧膠囊 + 骨關(guān)節(jié)炎��； 參考：《吉林大學(xué)》2015年碩士論文

【摘要】：目的根據(jù)炎痛寧膠囊處方依據(jù),在肯定臨床療效的基礎(chǔ)上,進(jìn)行該藥物抗炎作用及毒理學(xué)安全性評(píng)價(jià)的實(shí)驗(yàn)研究,研究該方抗炎鎮(zhèn)痛、活血化瘀作用及對(duì)大鼠膠原誘導(dǎo)性關(guān)節(jié)炎(CIA)損傷的治療作用并進(jìn)行比格犬長(zhǎng)期毒性實(shí)驗(yàn)以評(píng)價(jià)藥物安全性。方法采用小鼠醋酸扭體反應(yīng)、甲醛刺激大鼠足跖試驗(yàn)等動(dòng)物模型觀察炎痛寧膠囊的鎮(zhèn)痛作用;采用小鼠巴豆油性耳腫、小鼠腹腔毛細(xì)血管通透性、大鼠角叉菜膠足腫、大鼠棉球肉芽腫實(shí)驗(yàn)動(dòng)物模型,觀察炎痛寧膠囊的抗炎作用;建立血瘀模型,觀察炎痛寧膠囊的活血化瘀作用;建立大鼠CIA模型,觀察炎痛寧膠囊對(duì)CIA大鼠足腫脹和踝關(guān)節(jié)局部病理?yè)p傷的治療作用。將炎痛寧膠囊以3種劑量通過(guò)口服方法對(duì)比格犬進(jìn)行持續(xù)9個(gè)月的重復(fù)給藥,觀察藥物對(duì)動(dòng)物一般體征、飲食、肛溫、體重的影響,同時(shí)進(jìn)行尿液、血液學(xué)、血液生化、心電圖、眼科等檢查,在給藥結(jié)束和停藥恢復(fù)后進(jìn)行大體剖檢并進(jìn)行組織病理學(xué)檢查以及骨髓檢查等,以評(píng)價(jià)藥物的毒性。結(jié)果1.炎痛寧膠囊對(duì)化學(xué)刺激引起的疼痛有明顯的鎮(zhèn)痛作用,可顯著減少甲醛刺激致大鼠Ⅱ相疼痛舔足、抖足、抬足次數(shù),表明炎痛寧膠囊具有明顯鎮(zhèn)痛作用,對(duì)溫?zé)岽碳ひ鸬奶弁礋o(wú)明顯的鎮(zhèn)痛作用,其作用機(jī)制可能通過(guò)外周機(jī)制介導(dǎo)。2.炎痛寧膠囊對(duì)巴豆油致小鼠耳腫脹模型、角叉菜膠致大鼠足腫試驗(yàn)、毛細(xì)血管通透性試驗(yàn)及棉球肉芽腫試驗(yàn)均有明顯的抗炎作用,表明炎痛寧膠囊對(duì)急性炎癥和慢性炎癥具有顯著的抑制作用。3.炎痛寧膠囊對(duì)對(duì)側(cè)足的踝關(guān)節(jié)腫脹有顯著的抑制作用,顯著改善模型大鼠耳、鼻、尾、爪等部位的繼發(fā)性病變,表明炎痛寧膠囊對(duì)Ⅱ型膠原性關(guān)節(jié)炎有顯著的治療作用。4.炎痛寧膠囊能夠顯著減輕滑膜細(xì)胞增生,明顯減輕滑膜組織充血水腫、血管增生和浸潤(rùn)炎細(xì)胞數(shù)量、血管翳的形成。5.比格犬口服重復(fù)給予炎痛寧0.67、2.0、6.0g生藥/kg劑量9個(gè)月,各給藥組動(dòng)物與生理對(duì)照組比較,一般觀察、體重、肛溫、血液學(xué)、血清生化、尿液生化、心電圖檢查以及眼科檢查等均未見(jiàn)明顯藥物毒性作用;給藥結(jié)束及恢復(fù)期結(jié)束時(shí)骨髓檢查、大體解剖、臟器重量以及組織病理學(xué)檢查等也均未見(jiàn)明顯藥物毒性作用。結(jié)論炎痛寧膠囊具有明顯的鎮(zhèn)痛、抗炎作用,對(duì)炎性疼痛作用最好,且呈現(xiàn)一定的量效關(guān)系,其鎮(zhèn)痛部位在外周;對(duì)CIA大鼠有顯著地治療作用,可減輕炎癥及組織損傷,減少炎癥介質(zhì)的釋放,減輕局部炎癥,改善關(guān)節(jié)腫脹,對(duì)減輕組織損傷,修復(fù)骨質(zhì)破壞,對(duì)恢復(fù)機(jī)體生理功能有積極意義。并且由比格犬9個(gè)月長(zhǎng)期毒性試驗(yàn)可以檢測(cè)該藥物對(duì)動(dòng)物一般觀察、飲食觀察、體重、肛溫、心電圖、尿液、血液學(xué)、血液生化、尿液生化、大體解剖學(xué)、組織病理學(xué)的影響,從而評(píng)價(jià)了藥物的安全性。結(jié)果表明,炎痛寧膠囊有顯著的活血化瘀、抗炎鎮(zhèn)痛的作用,同時(shí)純中藥制劑避免了動(dòng)物注射或口服甾體或非甾體抗炎藥后消化系統(tǒng)、內(nèi)分泌系統(tǒng)及骨關(guān)節(jié)系統(tǒng)的強(qiáng)烈毒性作用。炎痛寧膠囊補(bǔ)肝腎、祛風(fēng)濕,活血通絡(luò)充分發(fā)揮扶正固本的作用,與其標(biāo)本兼治的治則一致。本研究為推廣和探索骨關(guān)節(jié)炎治療的新途徑、創(chuàng)新新的治療骨關(guān)節(jié)炎新藥提供思路和方法。
[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.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類(lèi)號(hào)】：S853.7

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本文編號(hào)：2054864