dl-3-正丁基苯酞软胶囊治疗轻中度急性缺血性脑卒中的开放临床研究

目的 观察国家Ⅰ类新药dl-3-正丁基苯酞软胶囊对轻中度急性缺血性脑卒中的疗效及安全性。方法对急性缺血性脑卒中患者进行随机对照或开放临床试验，参加随机试验的受试者依服药方法不同再分为3次／d给药（200mg／次）和2次／d给药（200mg／次）两个亚组；开放试验受试者均3次／d给药（200mg／次）。所有受试者基础用药均为复方丹参注射液。分别于治疗后第11天和第21天进行神经功能缺损评分及日常生活活动能力量表评分，观察和记录不良事件。结果（1）随机对照试验共入选28例患者，经dl-3-正丁基苯酞软胶囊治疗后，A组（3次／d给药）有效率为83．33％（15／18），B组（2次／d给药）40．00％（4／10），组间差异有统计学意义（P〈0．05）；A组治疗第11天和第21天神经功能缺损评分和日常生活活动能力量表评分与B组比较，差异有统计学意义（P〈0．05或P〈0．01）。开放试验入选患者34例，与随机试验28例合计进行总体疗效评估。（2）总体疗效评估显示，总有效率为72．58％（45／62）；与治疗前相比，治疗后第11天神经功能缺损评分明显减少，日常生活活动能力量表评分明显增加（均P〈0．01）；治疗后第21天神经功能缺损评分和日常生活活动能力量表评分优于第11天（均P〈0．01）。（3）RE用dl-3-正丁基苯酞软胶囊后的主要不良反应为丙氨酸转氨酶及天冬氨酸转氨酶水平轻中度升高，发生率为4．62％（3／65），停药后可恢复至正常水平。结论dl-3-正丁基苯酞软胶囊对轻中度急性缺血性脑卒中疗效显著，不良反应少且为可逆性，临床应用安全；3次／d用药组疗效优于2次／d用药组。

The randomized study on dl-3-butylphthalide in acute mild or moderate ischemic stroke

Objective To further assess the efficacy and safety of national new drug dl-3-butylphthalide (EBP) soft capsules in the treatment of acute mild or moderate ischemic stroke. Methods The acute ischemic stroke patients were enrolled in the randomly controlled or open clinical study. In randomized control trial the patients were randomly divided into two groups according to different dose administration: group A (EBP 200 mg, tid) and group B (EBP 200 mg, bid ). In open clinical trial the patients were administrated EBP 200 mg tid. The foundamental medication of all the patients was the Compound Radix Salviae Miltiorrhizae injectio. The rating scale score of neural function defect and activity of daily life were adopted for evaluation in this study on the 11 day and the 21 day after treatment, adverse effects were observed. Results 1) In the randomized controlled trial 28 patients were enrolled. After EBP treatment, the clinical effective rate in group A was 83.33% (15/18) and in group B was 40.00% (4/10). There was significant difference between the two groups (P < 0.05). There was significant difference between group A and B in the rating scale score of neural function defect and activity of daily life assessments on the 11 day and the 21 day after treatment (P < 0.05 or P < 0.01). In the opened trial 34 patients were enrolled, they were assessed combining with the 28 patients in the randomized trial for total therapeutic effect evaluation. 2) Total therapeutic effect evaluation: the total effective rate of all the 62 patients was 72.58% (45/62). Comparing with before treatment, the neural function defect score decreased significantly and activity of daily life score increased obviously on the 11 day after treatment (both P < 0.01). The recovery of the neural function and the activity of daily life on the 21 day after treatment were much better than those on the 11 day (both P < 0.01). 3) Drug safety evaluation demonstrated the main adverse effects of dl-3-butylphthalide soft capsules were liver dysfunction, (4.62%, 3/65), showing slightly or moderately increased level of alanine aminotransferase and aspartate aminotransferase, but the levels were returned normal after withdrawal the medications. Conclusion dl-3-butylphthalide soft capsules show significant effective on mild and moderate acute ischemic stroke with few reversible adverse effects, it is safe in clinical medication. The effect of tid medication is superior to that bid administration.