丁苯肽注射液临床治疗急性脑梗死的有效性及安全性评估

  本文关键词：丁苯肽注射液临床治疗急性脑梗死的有效性及安全性评估，由笔耕文化传播整理发布。

        目的：脑血管病是神经系统常见病和多发病，已成为我国城市和农村人口的第一位致残和死亡原因，且发病率有逐年增高的趋势，无论给社会还是家庭都带来了沉重的负担。脑卒中包括缺血性卒中和出血性卒中，其中急性脑梗死占全部卒中患者的70％～80％，缺血性卒中急性期的治疗直接影响预后，故其越来越受到人们的关注和重视。目前相应的处理和治疗包括卒中单元、动静脉溶栓、动脉取栓、抗血小板聚集、抗凝、神经保护、外科手术等，其疗效部分得到临床肯定，但有的仍存在争议。可是，上述疗法都不能很好的起到保护缺血半暗带的作用。为此，我国科学工作者一直在寻找一种保护缺血半暗带的药物，能够多环节的阻断脑缺血损伤机制。1978年，杨峻山从芹菜仔中提取出正丁基苯酞；1980年，杨靖华用化学方法合成了正丁基苯酞。90年代，著名神经药理学家冯亦璞对丁苯酞进行了一系列的深入研究，发现了其脑保护的作用。2001年，丁苯酞软胶囊(恩必普)正式面世，陆续进行了I、Ⅱ、Ⅲ期临床试验，证实其在急性缺血性卒中的治疗中，有效率高达73．2％，可阻断缺血性卒中所致脑损伤的多个病理环节，具有较强的抗脑缺血作用，可明显缩小脑组织的梗塞面积，减轻脑水肿，改善脑的能量代谢和缺血组织的微循环和脑血流量，抑制神经细胞凋亡，并具有抗血小板聚集和抗血栓形成的作用，从而达到改善并最大程度恢复神经功能的目的。根据临床需求，石药集团研发出了丁苯酞注射液。目前Ⅰ期、Ⅱ期、Ⅲ期临床已经完成，本实验是对其在真实世界中治疗急性缺血性卒中的进一步研究。方法：观察急性脑梗死患者100例，采用随机对照，自身平行对照研究，将脑梗死患者随机分成对照组和丁苯酞组(丁苯酞50mg／d)，用药14天，观察3个月。主要疗效指标为治疗第7天、第14天时的NIHSS,第3个月的Rankin量表评估。安全性指标用血常规，尿常规，便常规,凝血功能，肝功能，肾功能,血糖,心电图。结果：1入选100例试验对象，其中60例患者为丁苯酞治疗组，40例患者为对照组，试验过程中无脱落病人。2入选两组病人的一般情况、基本特征、既往病史和发病开始时的症状评分等无明显统计学差异(P>0．05)，具有可比性。3疗效分析。对照组和丁苯酞治疗组组内不同时期不同评分两两进行比较，即第0天与第7天，第0天与第14天，第7天与第14天间NIHSS比较，结果显示有显著统计学差异(P<0．05)，第0天与3个月间Rankinscore比较，结果显示有显著统计学差异(P<0．01).表明对照组和丁苯酞组患者，伴随病程的延长，神经症状均得到改善。丁苯酞组在治疗后第7天和第14天评分分别与对照组比较，，结果显示两组疗效指标NIHSS具有显著差异性(P值分别为O．045和0．037）；丁苯酞组在治疗后第3个月的Rankin评分与对照组比较，同样具有显著差异性（P值为O．007）．这说明丁苯酞组与对照组相比，能明显改善评分，对急性脑梗死有肯定的疗效。4安全性分析。对照组和丁苯酞组患者在治疗前均进行血常规、肝功能、肾功能、凝血功能、尿常规、粪常规和心电图检查，均为正常。所观察的100例患者中有9例出现了不良事件。其中对照组3例，表现为ALT或（和）AST升高,判断为可能与口服他汀类降脂药有关，停药后好转。丁苯酞组共出现6例，四肢乏力和浑身虚汗1例，心率减慢1例，转氨酶ALT或（和）AST升高4例，心率变慢者判断为与试验用药可能有关，其余5例与用药可能无关。随访均恢复正常，完成试验研究。两组间总不良事件发生率的比较P为0.669，无统计学意义，说明丁苯酞组与对照组比较不良事件发生率无明显差异。结论：丁苯酞注射液在真实世界中治疗急性缺血性卒中安全有效，是一种安全、有效且长期受益的新药。

    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.

丁苯肽注射液临床治疗急性脑梗死的有效性及安全性评估

摘要4-6ABSTRACT6-8前言9材料与方法9-12结果12-14附图14-15附表15-19讨论19-23结论23-24参考文献24-26综述 治疗急性脑梗死的有效药物丁苯酞注射液26-34    参考文献32-34致谢34-35个人简历35

  本文关键词：丁苯肽注射液临床治疗急性脑梗死的有效性及安全性评估，由笔耕文化传播整理发布。