一种促进神经损伤修复的药物组合物治疗22例ALS患者1年后的疗效观察

目的观察一种促进神经损伤修复的药物组合物治疗肌萎缩侧索硬化症(ALS)患者的疗效。 方法选取2015年4月至2017年9月江苏大学附属武进医院及苏州高新区人民医院收治的22例ALS患者为研究对象进行前瞻性自身对照研究，其中男性10例，女性12例；年龄34～68岁，平均年龄(51.64 ± 9.28)岁。在常规综合治疗基础上，将一种促进神经损伤修复的药物组合物[精氨酸1.5～5 g，异亮氨酸1.5～5 g，亮氨酸2.5～7.5 g，赖氨酸1.5～5 g，蛋氨酸0.25～1.5 g，苯丙氨酸0.25～1.5 g，苏氨酸1.5～5 g，色氨酸0.25～1.5 g，缬氨酸2.5～7.5 g，组氨酸1.5～4 g，甘氨酸1.5～4 g，丙氨酸1.5～5 g，脯氨酸1.5～4 g，天冬酰胺0.05～1.5 g，半胱氨酸0.05～1.5 g，谷氨酸1.5～5 g，丝氨酸0.25～2.5 g，酪氨酸0.05～1.5 g，L～鸟氨酸0.25～4 g，天冬氨酸0.5～2.5 g；维生素(维生素B₁ 1～2 mg，维生素B₂ 1～2 mg，维生素B₆ 3～10 g，维生素C 1～3 g)]配制在1个三升输液袋内进行静脉输注，1次/d，28 d为1个疗程，休息2周后行第2个疗程，持续治疗时间≥4个疗程或6个月。观察患者治疗前后及随访的国际肌萎缩侧索硬化症改良功能评分量表(ALSFRS-R)评分、疾病进展率及症状体征等变化情况。 结果本组22例ALS患者中死亡1例(4.55%)，为疾病晚期呼吸衰竭。肌肉萎缩好转、肌力增加3例(13.6%)，舌肌萎缩、构音障碍好转1例(4.5%)，流涎好转2例(9.1%)，吞咽功能改善1例(4.5%)，四肢活动度增加2例(9.1%)，1例(4.5%)不能站立和行走的患者可搀扶站立。各阶段ALSFRS-R评分波动范围：首次门诊时为18.0～44.0分，治疗6个月时为18.0～41.0分，末次治疗时为12.0～39.0分之间，末次随访时为6.0～38.0分。治疗6个月时ALSFRS-R评分与治疗前比较，差异无统计学意义[24.50(12.3)分比27.15(14.7)分，Z＝-1.183，P>0.05]，6例(27.3%)患者的ALSFRS-R评分上升，4例(18.2%)评分不变，12例(54.5%)评分下降。末次治疗时ALSFRS-R评分与治疗前相比有所下降[23.50(6.0)分比27.15(14.7)分，Z＝－2.557，P>0.05]，但仍有6例(27.3%)患者的评分上升。治疗6个月和末次治疗时的疾病进展率虽与治疗前的差异无统计学意义[0.521(0.563)分/月比0.673(0.716)分/月，Z＝－1.834；(0.702±0.469)分/月比(0.716±0.440)分/月，t＝0.259。P均>0.05]，但仍分别有72.7%(16/22)和54.5%(12/22)的患者疾病进展率较前下降。对所有患者随访至首次治疗后1年以上发现，其ALSFR-R评分4例(18.2%)上升，1例(4.5%)不变，17例(77.3%)下降，且疾病进展率低于治疗前[(0.584±0.372)分/月比(0.716±0.440)分/月，t＝2.706，P<0.05]。经过长期规范化治疗的患者，即使停止用药一段时间，仍然有72.7%(16/22)患者的疾病进展速率得以减缓。 结论该促进神经损伤修复的药物组合物能在整体上为ALS患者提供机体新陈代谢的底物、辅酶与强劲的动能，通过促进机体酶与氨基酸代谢以及血液循环，使受损、变性的神经系统功能得到一定程度的修复，增强了神经元的存活能力，从而延缓疾病发展，改善病情与临床症状。新疗法的确无毒无害无副作用，重复性好。

Therapeutic effect of a pharmaceutical composition on promoting nerve repair in amyotrophic lateral sclerosis: report of twenty-two cases with follow-up for one year

ObjectiveTo observe the efficacy of a pharmaceutical composition for promoting nerve repair in patients with amyotrophic lateral sclerosis (ALS). MethodsTwenty-two patients with ALS admitted to Affiliated Wujin Hospital of Jiangsu University and the People's Hospital of SND from April 2015 to September 2017 were enrolled in this study. The prospective self-controlled study included 10 males and 12 females, aged 34 to 68 years, with average age (51.64±9.28) years. On the basis of conventional comprehensive treatment, the pharmaceutical composition [The main components: arginine 1.5-5 g, isoleucine 1.5-5 g, lysine 2.5-7.5 g, methionine 0.5-1.5 g, phenylalanine 0.5-5 g, tryptophan 0.5-1.5 g, valine 2.5-7.5 g, histidine 1.5-4 g, glycine 1.5-4 g, alanine 1.5-5 g, proline 1.5-4 g, asparagine 0.05-1.5 g, cysteine 0.05-1.5 g, cysteine 1.5-5 g, serine 0.25-2.5 g, Tyrosine 0.05-1.5 g, L-ornithine 0.25-4 g, aspartic acid 0.5-2.5 g. Vitamins (vitamin B₁ 1-2 mg, vitamin B₂ 1-2 mg, vitamin B₆ 3-10 g, vitamin C 1-3 g)] were prepared in a three-liter infusion bag for intravenous infusion, once a day for 28 days for a course of treatment, the next course should be followed after a drug withdrawal for 2 weeks, and the continuous treatment lasted at least for 4 courses or 6 months. The changes of the amyotrophic lateral sclerosis modified functional rating scale-revised (ALSFRS-R), disease progression rate and symptoms and signs were observed in all patients pre- and post-treatment. ResultsOne of the 22 patients with ALS (4.55%) died from the advanced respiratory failure in the terminal phase of disease. Symptoms of muscle atrophy and muscle strength were improved in 3 cases (13.6%). Symptoms of atrophy of tongue muscle and dysarthria were improved in 1 case (4.5%). Symptoms of salivation were improved in 2 cases (9.1%). Swallowing function were improved in 1 case (4.5%). Limb activity were increased in 2 cases (9.1%). 1 patient (4.5%) who could not stand and walk restored the standing ability (under other’s support) after treatment. The fluctuation ranges of ALSFRS-R scores in each stage were 18.0~44.0 points for the first outpatient visit, 18.0~41.0 points for the 6 months of treatment, 12.0~39.0 points for the last treatment, and 6.0~38.0 points for the last follow-up. After 6 months of treatment, the ALSFRS-R score was not significantly different from that before treatment [24.50(12.3) points vs. 27.15(14.7)points, Z =-1.183, P>0.05], while 6 patients (27.3%) had an increased ALSFRS-R score, 4 patients (18.2%) remained the same, and 12 patients (54.5%) had a lower one. The ALSFRS-R score after the last treatment decreased compared with that before treatment [23.50 (6.0) points vs.27.15 (14.7) points, Z=-2.557, P>0.05]; however, 6 cases (27.3%) still had an increased score. Although the disease progression rate at neither 6 months of treatment nor the last treatment was statistically different from that before treatment [0.521 (0.563) points/month vs. 0.673 (0.716) points/month, Z=-1.834, P>0.05], they still got a lower rate of disease progression in 72.7% (16/22) and 54.5% (12/22) patients. All patients were followed up to more than 1 year since the first treatment, and the ALSFR-R score increased in 4 (18.2%), 1 (4.5%) remained unchanged, and 17 (77.3%) decreased, but the progression rate of the decline was still slower as compared with those before treatment [(0.584±0.372) points/month vs. (0.716±0.440) points/month, t = 2.706, P<0.05]. The last follow-up showed that 72.7% (16/22) of patients who had undergone a long-term standardized treatment still had a slower rate of disease progression even if they stopped the drug delivery for a while. ConclusionsThis pharmaceutical composition for promoting nerve repair can provide the ALS patients with metabolic substrate, coenzyme and energy as a whole, make the damage and degeneration of the nervous system repaired in a certain extent by promoting enzyme and amino acid metabolism and blood circulation, enhance the survival of neurons, to result in delaying the development of the disease and improving the condition and clinical symptoms. The new treatment is indeed non-toxic, harmless and reproducible with no side effects.