本文關(guān)鍵詞：丁苯肽注射液臨床治療急性腦梗死的有效性及安全性評估，由筆耕文化傳播整理發(fā)布。

        目的：腦血管病是神經(jīng)系統(tǒng)常見病和多發(fā)病，已成為我國城市和農(nóng)村人口的第一位致殘和死亡原因，且發(fā)病率有逐年增高的趨勢，無論給社會還是家庭都帶來了沉重的負(fù)擔(dān)。腦卒中包括缺血性卒中和出血性卒中，其中急性腦梗死占全部卒中患者的70％～80％，缺血性卒中急性期的治療直接影響預(yù)后，故其越來越受到人們的關(guān)注和重視。目前相應(yīng)的處理和治療包括卒中單元、動靜脈溶栓、動脈取栓、抗血小板聚集、抗凝、神經(jīng)保護(hù)、外科手術(shù)等，其療效部分得到臨床肯定，但有的仍存在爭議�？墒牵鲜霪煼ǘ疾荒芎芎玫钠鸬奖Ｗo(hù)缺血半暗帶的作用。為此，我國科學(xué)工作者一直在尋找一種保護(hù)缺血半暗帶的藥物，能夠多環(huán)節(jié)的阻斷腦缺血損傷機(jī)制。1978年，楊峻山從芹菜仔中提取出正丁基苯酞；1980年，楊靖華用化學(xué)方法合成了正丁基苯酞。90年代，著名神經(jīng)藥理學(xué)家馮亦璞對丁苯酞進(jìn)行了一系列的深入研究，發(fā)現(xiàn)了其腦保護(hù)的作用。2001年，丁苯酞軟膠囊(恩必普)正式面世，陸續(xù)進(jìn)行了I、Ⅱ、Ⅲ期臨床試驗，證實其在急性缺血性卒中的治療中，有效率高達(dá)73．2％，可阻斷缺血性卒中所致腦損傷的多個病理環(huán)節(jié)，具有較強(qiáng)的抗腦缺血作用，可明顯縮小腦組織的梗塞面積，減輕腦水腫，改善腦的能量代謝和缺血組織的微循環(huán)和腦血流量，抑制神經(jīng)細(xì)胞凋亡，并具有抗血小板聚集和抗血栓形成的作用，從而達(dá)到改善并最大程度恢復(fù)神經(jīng)功能的目的。根據(jù)臨床需求，石藥集團(tuán)研發(fā)出了丁苯酞注射液。目前Ⅰ期、Ⅱ期、Ⅲ期臨床已經(jīng)完成，本實驗是對其在真實世界中治療急性缺血性卒中的進(jìn)一步研究。方法：觀察急性腦梗死患者100例，采用隨機(jī)對照，自身平行對照研究，將腦梗死患者隨機(jī)分成對照組和丁苯酞組(丁苯酞50mg／d)，用藥14天，觀察3個月。主要療效指標(biāo)為治療第7天、第14天時的NIHSS,第3個月的Rankin量表評估。安全性指標(biāo)用血常規(guī)，尿常規(guī)，便常規(guī),凝血功能，肝功能，腎功能,血糖,心電圖。結(jié)果：1入選100例試驗對象，其中60例患者為丁苯酞治療組，40例患者為對照組，試驗過程中無脫落病人。2入選兩組病人的一般情況、基本特征、既往病史和發(fā)病開始時的癥狀評分等無明顯統(tǒng)計學(xué)差異(P>0．05)，具有可比性。3療效分析。對照組和丁苯酞治療組組內(nèi)不同時期不同評分兩兩進(jìn)行比較，即第0天與第7天，第0天與第14天，第7天與第14天間NIHSS比較，結(jié)果顯示有顯著統(tǒng)計學(xué)差異(P<0．05)，第0天與3個月間Rankinscore比較，結(jié)果顯示有顯著統(tǒng)計學(xué)差異(P<0．01).表明對照組和丁苯酞組患者，伴隨病程的延長，神經(jīng)癥狀均得到改善。丁苯酞組在治療后第7天和第14天評分分別與對照組比較，，結(jié)果顯示兩組療效指標(biāo)NIHSS具有顯著差異性(P值分別為O．045和0．037）；丁苯酞組在治療后第3個月的Rankin評分與對照組比較，同樣具有顯著差異性（P值為O．007）．這說明丁苯酞組與對照組相比，能明顯改善評分，對急性腦梗死有肯定的療效。4安全性分析。對照組和丁苯酞組患者在治療前均進(jìn)行血常規(guī)、肝功能、腎功能、凝血功能、尿常規(guī)、糞常規(guī)和心電圖檢查，均為正常。所觀察的100例患者中有9例出現(xiàn)了不良事件。其中對照組3例，表現(xiàn)為ALT或（和）AST升高,判斷為可能與口服他汀類降脂藥有關(guān)，停藥后好轉(zhuǎn)。丁苯酞組共出現(xiàn)6例，四肢乏力和渾身虛汗1例，心率減慢1例，轉(zhuǎn)氨酶ALT或（和）AST升高4例，心率變慢者判斷為與試驗用藥可能有關(guān)，其余5例與用藥可能無關(guān)。隨訪均恢復(fù)正常，完成試驗研究。兩組間總不良事件發(fā)生率的比較P為0.669，無統(tǒng)計學(xué)意義，說明丁苯酞組與對照組比較不良事件發(fā)生率無明顯差異。結(jié)論：丁苯酞注射液在真實世界中治療急性缺血性卒中安全有效，是一種安全、有效且長期受益的新藥。

    Objectives: Cerebrovascular disease is a common and frequently-occurring disease of the nervous system. It has became the first factor ofcripple and death in China’s urban and rural population.The morbidity hasincreased year by year,bringing heavy burden on the family and society.Stroke includes ischemic stroke and hemorrhagic stroke, the acute cerebralinfarction accounted for70%-80%of all stroke patients. The treatment ofacute cerebral infarction influences the prognosis directly, so it has attractedmore and more attention. At present,the corresponding processing andtreatment include stroke unit, arterial and venous thrombolysis, arterialembolectomy, anti-platelet aggregation, anticoagulant, neuroprotective,surgery and so on, some of them are clinically proved to be efficacious butsome remains controversial.However, these therapies are not play a well role in protection of theischemic penumbra. To this end, our scientists have been looking for a drug toprotect the ischemic penumbra, which be able to block the cerebral ischemicinjury mechanisms from multi-link. In1978, Yang Jun-Shan extracted n-butylphthalide from celery seed. In1980, Yang Jinghua synthetized n-butylphthalide by chemical methods; In the1990s, the famous nervepharmacologist Ping did a series of in-depth research on butyl phthalide, andfound that its effectiveness of brain protection. In2001, the soft capsuleButylphthalide (NBP) officially available, I, Ⅱ, Ⅲclinical trials were carriedout in succession, confirmed its efficiency up to73.2%in the treatment ofacute ischemic stroke. It can block multiple pathological aspects of braindamage caused by ischemic stroke, with a strong anti-cerebral ischemia. It canalso significantly reduce the infarct size of focal cerebral ischemia, cerebraledema, improve brain energy metabolism, ischemic areas microcirculation and cerebral blood flow; meanwhile, it can inhibit neuronal apoptosis and play arole in anti-thrombotic and anti-platelet aggregation, so as to improve andmaximize the purpose of restoring nerve function.Based on clinical needs, CSPC developed Butylphthalide injection. Ⅰ,Ⅱ, Ⅲ, clinical trials has been completed, the purpose of ourresearch is toevaluate the efficacy and safety of dl-3-n-butylphthalide injection in the realworld treatment of acute cerebral infarction.Methods:100patients with acute cerebral infarction were followed up ina Randomized and parallel controlled study．Under the premise of basictreatment,60patients were given the test drug ButylphthalideIn injection(Butylphthalide50mg/d). Observed the100cases of patients for3months.Rankin scales were get as major index to evaluate therapeutic affection in the3months after treatment and NIHSS get on the7th and14th day aftertreatment as secondary therapeutic effect index．ECG, blood clotting, liverfunction, kidney function, blood glucose, and the routines of blood, urine andstool were used to evaluate medical safety.Results:1100patients include40patients in the control group，no Patients wereexcluded.2There was no significant difference in patients’characteristics，historyand initial symptoms, NIHSS and Rankin scales between control andtreatment group.3Comparing the score at different periods within the group of the controlone and the treatment one，that is NIHSS comparison between0th day and7thdays,0th day and14th days,7th days and14th days，the results show that it isof statistically significant difference (P <0.05). Comparing the Rankin scorebetween0day and3-month, the results show that there is a statisticallysignificant difference (P<0.01). Accompanied by the duration of the extension,neurological symptoms of the control group and the treatment group were allimproved. Comparing the scores of NIHSS on the7th day,14th day and theRankin score in the3months between dl-3-n-butylphthalide and the control, the results show that there is also a statistically significant difference (P<0.01).This show that dl-3-n-butylphthalide can significantly improve the ratings andhave a positive effect on acute cerebral infarction.4Their hepatic and renal functions,blood and urine routine test,ECG(electrocardiogram)and blood clotting were all in normal state beforecuring．There were7patients，3in the control group and4in the test groups,showing adverse events and those were uncommon hepatic function,hypodynamia, dyskinesia, and heart rate negative acceleration．Only thedecrease in heart rate case was judged as having possible some relationshipwith the test drug．The total7cases recovered normal．Comparing theincidence of adverse events between the two groups, p is0.669, with nostatistically significant.Conclusion: The Butylphthalide injection is a safe, effective and long-term benefit new drug in the real world treatment of acute ischemic stroke.

丁苯肽注射液臨床治療急性腦梗死的有效性及安全性評估

摘要4-6ABSTRACT6-8前言9材料與方法9-12結(jié)果12-14附圖14-15附表15-19討論19-23結(jié)論23-24參考文獻(xiàn)24-26綜述 治療急性腦梗死的有效藥物丁苯酞注射液26-34    參考文獻(xiàn)32-34致謝34-35個人簡歷35

  本文關(guān)鍵詞：丁苯肽注射液臨床治療急性腦梗死的有效性及安全性評估，由筆耕文化傳播整理發(fā)布。