CN107115332A - 一种用于治疗运动神经元病的组合物及其用途 - Google Patents
一种用于治疗运动神经元病的组合物及其用途 Download PDFInfo
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Abstract
本发明属于制药领域,公开了一种用于治疗运动神经元病的组合物及其用途。每单位该组合物含有:相当于L-鸟氨酸含量为0.5~8g的L-鸟氨酸盐,天冬氨酸1~5g,维生素B6 6-20g。该组合物能够改善甚至逆转运动神经元病的进展,可用于制备治疗运动神经元病的药物或保健品。该组合物长期使用安全无副作用,治疗费用低,效果好,适于临床推广。
Description
技术领域
本发明属于制药领域,涉及一种用于治疗运动神经元病的组合物及其用途。
背景技术
运动神经元病(motor neuron disease,MND),是一组病因尚未明确的选择性侵犯脊髓前角细胞、脑干运动神经元、皮质椎体细胞及椎体束的慢性进行性变性疾病,其病理特征为进行性上、下运动神经元的变性、坏死及凋亡。临床上兼有上和(或)下运动神经元受损表现,为肌无力、肌肉萎缩和椎体束征的不同组合,最终常因呼吸衰竭至死,感觉和***功能一般不受影响。由于症状和体征的组合不同,形成不同类型的运动神经元病,包括肌萎缩侧索硬化(amyotrophic lateral sclerosis,ALS)、脊肌萎缩症(spinal muscularatrophy,SMA)、原发性侧索硬化(primary lateral sclerosis,PLS)和进行性延髓麻痹(progressive bulbar palsy,PBP)等,其中ALS是慢性运动神经元病的最常见类型,俗称“渐冻人症”。
目前对本病的病因及发病机制仍不明确。其中比较公认的有自由基氧化学说、兴奋性氨基酸毒性、神经营养因子障碍、自身免疫机制、病毒感染及环境因素等。各种假说均有一定的证据支持,当前较为集中的认识是在遗传背景基础上是氧化损害和兴奋性毒性作用共同损害了运动神经元,主要是影响了线粒体和细胞骨架的结构和功能。
“渐冻人症”目前尚无明确有效的治疗方法,患者的平均存活时间只有2-5年。据统计,到2010年底,在我国大约有20多万渐冻人患者。
目前对于运动神经元病的治疗措施主要为了减轻症状、延缓病情的进展及提高患者的生存质量。对症用药主要有:力如太(又叫力鲁唑,Riluzole)——目前唯一一个美国食品药品监督局(FDA)批准的用于治疗ALS的药物,是一种抗谷氨酸毒性的药物,也是目前唯一一个证明对动物模型有效、临床有效的药物,其可以延缓病情发展,也仅仅能使患者的生存期延长半年左右。其他用药还有:甲钴安、维生素B族、维生素E及各种神经营养药物等。中医将其归属于“痿症”,病机为五脏虚损、精津不足、气血亏虚、肌肉筋脉失养、脾胃虚损。在治疗上辩证论治,针药并举,注重以调理脾胃功能,益脾补虚,调补心、肺、肝、肾四脏虚损。使患者症状得到改善,病情发展延缓,运动神经元病痛得到减轻。
目前尚无一种对运动神经元病安全有效且成本低廉的药物或保健品。
发明内容
本发明的目的是提供一种用于治疗运动神经元病的组合物。
本发明的另一目的是提供上述组合物的用途。
本发明的目的是通过下列技术方案实现的:
一种用于治疗运动神经元病的组合物,每单位该组合物中含有:相当于L-鸟氨酸含量为0.5~8g的L-鸟氨酸盐,天冬氨酸1~5g,维生素B66-20g。L-鸟氨酸盐优选L-鸟氨酸盐酸盐。
所述的组合物,每单位该组合物中还含有下列物质中的一种或多种:精氨酸,异亮氨酸,亮氨酸,赖氨酸,蛋氨酸(甲硫氨酸),苯丙氨酸,苏氨酸,色氨酸,缬氨酸,组氨酸,甘氨酸,丙氨酸,脯氨酸,天冬酰胺,半胱氨酸,谷氨酸,丝氨酸,酪氨酸,维生素B1,维生素B2,维生素B3,泛酸,生物素,叶酸,维生素B12,维生素C。
上述各氨基酸的形式可以是氨基酸的各种可溶性盐或者其衍生物。其中赖氨酸可采用赖氨酸醋酸盐,半胱氨酸可采用N-乙酰-L-半胱氨酸,酪氨酸可采用N-乙酰-L-酪氨酸;
各氨基酸的用量分别是:精氨酸3~10g,异亮氨酸3~10g,亮氨酸5~15g,相当于赖氨酸含量为3~10g的赖氨酸醋酸盐,蛋氨酸0.5~3g,苯丙氨酸0.5~3g,苏氨酸3~10g,色氨酸0.5~3g,缬氨酸5~15g,组氨酸3~8g,甘氨酸3~8g,丙氨酸3~10g,脯氨酸3~8g,天冬酰胺0.1~3g,相当于半胱氨酸含量为0.1~3g的N-乙酰-L-半胱氨酸,谷氨酸3~10g,丝氨酸0.5~5g,相当于酪氨酸含量为0.1~3g的N-乙酰-L-酪氨酸;
维生素的用量分别是:维生素B12~4mg,维生素B22~4mg,维生素B320~40mg,泛酸6~10mg,生物素0.2~0.4mg,叶酸0.2~0.8mg,维生素B124~12μg;维生素C2-6g。
所述的组合物,每单位该组合物中含有:
异亮氨酸8.80g,亮氨酸13.60g,赖氨酸醋酸盐10.60g(相当于赖氨酸7.51g),蛋氨酸1.20g,苯丙氨酸1.60g,苏氨酸4.60g,色氨酸1.50g,缬氨酸10.60g,精氨酸8.80g,组氨酸4.70g,甘氨酸6.30g,丙氨酸8.30g,脯氨酸7.10g,天冬氨酸2.50g,天冬酰胺0.55g,N-乙酰-L-半胱氨酸0.80g(相当于半胱氨酸0.60g),谷氨酸5.70g,L-鸟氨酸盐酸盐1.66g(相当于L-鸟氨酸1.30g),丝氨酸3.70g,N-乙酰-L-酪氨酸0.86g(相当于酪氨酸0.70g),维生素B610g。进一步,每单位该组合物中还含有维生素C 4g。
上述组合物还可以含有适量的5%葡萄糖氯化钠注射液(5%GNS)或0.9%氯化钠注射液(0.9%NS)。
该组合物的剂型为药学上允许的任意剂型或保健品允许的任意剂型。进一步优选,该组合物的剂型为注射剂、口服液、片剂、颗粒剂、胶囊剂、冲剂。
该组合物在制备治疗运动神经元病的药物或保健品中的应用。
一种治疗运动神经元病的方法,该方法采用注射或口服的方式给予患者上述的组合物;所述注射方式优选静脉注射。
本发明所述的每单位组合物中各物质的含量也可以采用质量份等方式表述,不影响该组合物中各物质含量的比例关系。
本发明中各氨基酸优选L型氨基酸。
本发明组合物对运动神经元病的治疗机制探讨:
静息电位是指细胞在未受刺激时(静息状态下)存在于细胞膜内、外两侧的电位差。众所周知,静息电位存在于神经和肌肉纤维内。J.Bernstein于1902年首次提出神经细胞膜两边的K+分布的不相等以及膜对钾离子的选择通透性是静息电位的产生原因。静息神经细胞对K+是高通透的,对Na+则很低,正是这种选择性通透使膜内外形成K+浓度梯度而产生跨膜电位差。可见细胞膜内、外离子的不均匀分布以及在安静状态下对不同离子的通透性不同是静息电位产生的前提条件。细胞外的Na+浓度高于细胞内,而细胞内K+浓度远高于细胞外,因此在细胞膜的两侧存在离子浓度差;另外,还会存在电位差。离子的扩散动力就取决于浓度差和电位差,细胞在安静状态下,只是对K+有通透性,对Na+和其他离子的通透性很小。K+在浓度差的动力下向膜外扩散,由于K+是正离子,向外扩散形成的外正内负的电位差又会阻止K+的进一步扩散,当促使K+外流的浓度差动力和阻止K+外流的电位差阻力相等时,K+的外流停止,此时的跨膜电位称为K+平衡电位。影响静息电位水平的因素主要有:①细胞外K+浓度可影响静息电位的大小,如细胞外K+浓度升高,细胞内K+浓度差降低,K+外流的量减少,静息电位减少;②膜对K+和Na+的相对通透性可影响静息电位的大小,如膜对K+的通透性增大,则静息电位增大,如膜对Na+的通透性增大,则静息电位将减小;③钠泵活动的水平对静息电位有影响。
动作电位,是指可兴奋细胞受到刺激时,在静息电位的基础上产生的一次迅速可扩布性的电位变化。动作电位产生的机制为:细胞外的Na+浓度比细胞内高,Na+顺着浓度差就有内流的趋势,细胞在安静状态下,对Na+的通透性小,Na+内流的量也就很少。当细胞受到刺激后,细胞膜上少量的Na+通道被激活开放,Na+顺着浓度差和电位差内流,膜内的负电位值逐渐变小,发生去极化,当去极化到达一定的程度时,膜上钠通道大量被激活开放,大量的Na+内流,从而爆发动作电位。使膜对Na+通透性突然增大的临界膜电位,称为阈电位。阈电位比静息电位小约10-20mv,神经细胞的阈电位约为-55mv。刺激必须是膜内负电位值减少到阈电位时,才能爆发动作电位。由于Na+是顺着浓度差和电位差进行的扩散,Na+内流速度很快,膜内负电位值迅速变小、消失,并且进一步转为正电位,膜内形成的正电位对Na+内流形成电场阻力,阻止Na+内流,促使Na+内流的力量(浓度差)与阻止Na+内流的力量(电场阻力)相等时,Na+内流停止,这时动作电位达到最大幅值,即为Na+的电-化学平衡电位,形成动作电位的上升支,钠通道开放时间短,很快失活关闭,这时细胞膜对K+的通透性增大,大量K+顺着浓度差和电位差迅速外流,使膜内电位从正值变为负值,出现复极化,恢复到静息状态水平,形成动作电位的下降支。简言之,动作电位的上升支就是Na+内流形成的电-化学平衡电位,动作电位的下降支就是K+外流形成的电-化学平衡电位。细胞在发生动作电位后,膜电位基本恢复到静息状态水平,但是离子分布没有恢复,细胞外有过多的K+,细胞内有过多的Na+,这时将激活细胞膜上的钠泵,通过钠泵的作用,将细胞外过多K+的泵入细胞内,同时将细胞内过多的Na+泵出细胞外,恢复原来的静息状态水平,为下一次兴奋做好准备。
氨基酸是构成生物体蛋白质并同生命活动有关的最基本的物质,是在生物体内构成蛋白质分子的基本单位,与生物的生命活动有着密切的关系。它在抗体内具有特殊的生理功能,是生物体内不可缺少的营养成分之一。其在人体内通过代谢可以发挥下列一些作用:①合成蛋白质及核酸;②变成酸、激素、抗体、肌酸等含氮物质;③转变为碳水化合物和脂肪;④氧化成二氧化碳和水及尿素,产生能量。
L-鸟氨酸是非蛋白氨基酸,在生物体内主要参与尿素循环,对体内氨态氮的排出有重要作用。在尿素循环中,氨甲酰磷酸合成酶Ⅰ是尿素循环中的酶,存在于线粒体中,以氨为氮源,需要N-乙酰谷氨酸,生成的氨甲酰磷酸用来合成尿素;氨甲酰磷酸合成酶Ⅱ存在于胞质溶胶中,利用谷氨酰胺作为氮源,不需要N-乙酰谷氨酸,合成的氨甲酰磷酸用来合成嘧啶。由氨甲酰磷酸合成酶Ⅰ催化的第一步反应是尿素循环的限速步骤。氨甲酰磷酸合成酶Ⅰ被N-乙酰谷氨酸别构酶活化。该代谢物是由谷氨酸和乙酰CoA在N-乙酰谷氨酸合成酶催化下合成。当氨基酸降解速率增加时,作为转氨作用的结果,谷氨酸的浓度也随之增加,谷氨酸浓度的增加促进了N-乙酰谷氨酸的合成,结果活化了氨甲酰磷酸合成酶,使尿素合成速率加快。因此氨基酸降解产生的过量氮,就被有效的排出体外。由于精氨酸是N-乙酰谷氨酸合成酶的激活剂,因此精氨酸浓度的增高,也会加速尿素的合成。
天冬氨酸通过脱氨生成草酰乙酸而促进三羧酸循环,故而天冬氨酸是三羧酸循环中的重要成分。并且天冬氨酸还在鸟氨酸循环和核苷酸合成中起重要作用,是多种氨基酸及嘌呤、嘧啶碱基的合成前体。它对细胞亲和力很强,可作为钾、镁离子载体,向心肌输送电解质,促进细胞去极化,维持心肌收缩能力,同时可降低心肌耗氧量,在冠状动脉循环障碍引起缺氧时,对心肌有保护作用。也就是说天冬氨酸能直接参与尿素循环并参与三羧酸循环及肝细胞内核酸的合成,有利于修复被损伤的肝细胞。此外,由于天冬氨酸对肝细胞内三羧酸循环代谢过程的间接促进作用,并提供能量代谢的中间产物,促进了肝细胞的能量生成,使被损伤的肝细胞的各项功能得以迅速恢复。所以L-鸟氨酸和天冬氨酸合用可以刺激肝尿素循环活性和促进谷氨酰胺合成,大大增强肝脏排毒功能,迅速降低血氨,促进肝细胞自身的修复和再生。因此,氨基酸在人体内的存在,不仅能提供合成蛋白质的重要原料,而且对于促进生长,进行正常代谢,维持生命提供了物质基础。
B族维生素是水溶性维生素,包括维生素B1、维生素B2、维生素B6、维生素B12、烟酸、泛酸、叶酸等,是推动体内代谢,把糖、脂肪、蛋白质等转化成热量时不可缺少的物质。它们具有协同作用,调节新陈代谢,增进免疫***促进细胞生长和***。维生素B6可能是所有维生素B族中最重要的一种。维生素B6又名吡哆素,包括吡哆醇、吡哆醛和吡哆胺3种化合物。在动物组织中吡哆醇可转化为吡哆醛或吡哆胺,且维生素B6多以吡哆醛和吡哆胺形式存在与动物组织中。吡哆醛和吡哆胺,吡哆醛磷酸和吡哆胺磷酸都可以互变,最后都以活性较强的吡哆醛磷酸和吡哆胺磷酸形式存在于组织中,参加转氨作用。一般人体的肌肉里含有全身70%~80%的维生素B6。维生素B6在蛋白、脂质和碳水化合物的代谢中发挥着关键的作用。所以,大量损耗维生素B6的人会出现包括氨基酸代谢紊乱。维生素B6是氨基酸的代谢与合成的重要辅酶,并参与不饱和脂肪酸的代谢等生理过程,是机体内许多重要酶***的辅酶,是动物正常发育、细菌和酵母繁殖所必需的营养成分。另外,维生素B6还是一种天然的利尿剂,利尿就能解毒,静脉输入维生素B65g,大约能利出尿液380ml左右。维生素B6是人体氨基酸代谢、神经递质γ-氨基丁酸(GABA)和谷氨酸(Glu)的辅酶,现已知肝脏有60多种酶需要维生素B6参与,在促进机体正常酶代谢方面起到十分重要的作用,且维生素B6在体内的半衰期短,很快就排出体外。并且吡哆醛磷酸还有一特殊的功能,其可以促进氨基酸和钾进入细胞的速率。
钾是体内最重要的无机阳离子之一,在机体电解质中的含量仅次于钠,其中98%存在于细胞内,存在于细胞外液的仅占2%,血清钾浓度为3.5-5.5mmol/L。细胞内外钾浓度相差悬殊是靠细胞膜Na+-K+-ATP酶耗能转运来维持的。钾是全身所有器官功能作用的重要物质基础,参与全身所有的器官作用。其生理功能有:①参与细胞内糖和蛋白质的代谢;②维持细胞内的渗透压和调节酸碱平衡;③维持细胞膜静息电位,静息膜电位主要取决于细胞膜对K+的通透性和细胞膜内外K+的浓度差;④维持神经肌肉的兴奋性,高钾使神经肌肉兴奋性增高,低钾使兴奋性降低;⑤维持正常心肌收缩运动的协调。
例如:乙酰胆碱的突触传递过程。乙酰胆碱是脊椎动物神经肌肉接头(运动终板)上的兴奋性神经递质。乙酰胆碱是在胆碱能神经元的轴突末梢轴浆中合成。胆碱和乙酰辅酶A在胆碱乙酰基转移酶的作用下生成乙酰胆碱。神经细胞不能合成胆碱,主要靠血循环供给,借助细胞膜上的专一性载体——胆碱转运体摄取到细胞中。肝脏中合成的胆碱酯、胶质细胞中储备的胆碱以及神经末梢释放的乙酰胆碱水解产生的胆碱也可以成为乙酰胆碱合成中胆碱的来源。并且乙酰胆碱合成后被包装在突触小泡内,每个小泡约有103-104分子的乙酰胆碱,就在突触前轴突质膜附近有大量这样的突触小泡。动作电位的到达,激发突触前膜大大增加对Ca2+的通透性,Ca2+顺其离子浓度梯度流入轴浆。由于细胞内Ca2+的增加,促进了突触小泡与质膜的融合,从而增加乙酰胆碱释放到突触间隙。通过这种机制,在对1个动作电位所引起的反应中,可有几百个突触小泡排出乙酰胆碱到一个典型的神经肌肉突触接头的突触间隙。结果是局部的乙酰胆碱浓度大大增加,足以使突触后细胞的质膜中的1种蛋白质即乙酰胆碱受体“感觉到”。这种神经递质结合到许多受体分子上,激发突触后细胞发生动作电位。乙酰胆碱随后为突触间隙中的1种称为乙酰胆碱酯酶迅速降解成乙酸和胆碱,同时突触后膜迅速恢复至静息电位。并且在这一过程中,乙酰胆碱的作用同时增加了膜对Na+和K+的通透性。由于突触后膜的电化学梯度比K+的大一些,结果Na+的向内流动导致去极化,使跨膜电位崩溃。只要有足够数目的受体分子结合了神经递质,这种跨膜电位的局部扰动就足以在受体所在的神经膜或肌膜上引发出1个新的动作电位。因而在一定时刻被占据受体的数目支配了Na+的内向流动量,以及由此决定的膜电位变化的大小。结合于突触后膜的乙酰胆碱酯酶迅速催化乙酰胆碱水解,递质-受体复合物的数目很快减少,膜复极化,准备接待新的动作电位触发突触前膜释放更多量子单位的乙酰胆碱。
一般神经元产生的静息电位、动作电位、发生器电位和突触电位都有赖于血脑屏障主动转运形成的离子梯度,而且神经冲动的传递和准确再现也有赖于血脑屏障对神经元和神经纤维的屏蔽作用。有资料显示,运动神经元病患者脑脊液中的谷氨酸水平比80%对照组高3倍。且细胞外过高的谷氨酸浓度,会过度刺激其受体,对中枢神经***产生明显的毒性作用。但是使用本发明后发现,脑脊液中的谷氨酸水平明显下降,运动神经元得到修复,患者症状明显得到改善。原因有以下一种或几种:①本发明中,体内过高的谷氨酸和本发明中的半胱氨酸以及甘氨酸可以生成谷胱甘肽,清除体内的自由基,减轻运动神经元病患者的症状。②在肝脏中,过高的谷氨酸在谷氨酸脱氢酶(辅酶是NAD+或NADP+)的作用下氧化脱氨基生成α-酮戊二酸和氨,过多的氨可以与谷氨酸结合生成谷氨酰胺,谷氨酰胺和本发明中的天冬氨酸在氨甲基酰磷酸合成酶Ⅱ作用下合成嘧啶核苷酸,并且谷氨酰胺也可以和本发明中的甘氨酸以及天冬氨酸合成嘌呤核苷酸,而且在肝脏胞液中谷氨酸与本发明中的甘氨酸和天冬氨酸参与嘌呤核苷酸从头合成,为体内核苷酸提供来源。嘧啶核苷酸和嘌呤核苷酸的合成,促进蛋白质合成,修复受损的神经元细胞,并且谷氨酸氧化脱氨基生成的多余氨由L-鸟氨酸激活肝细胞内尿素循环排出体外。③生成的谷氨酰胺能直接通过血脑屏障,分解成氨和谷氨酸,使大脑海马中兴奋性氨基酸谷氨酸有所增加。虽然在胞外过高的谷氨酸浓度对中枢神经***产生明显的毒性作用,但是胞内谷氨酸是哺乳动物中枢神经***含量最丰富的兴奋性神经递质,参与神经***多种重要功能的调节,对神经发育、突触可塑性的维持、神经元回路的形成及学***衡、使细胞膜静息电位增大、使神经肌肉兴奋性增高、使正常心肌收缩运动的得到协调。
总而言之,由于本发明中含有各种各样的氨基酸,其能够为血液提供新鲜的营养,通过氨基酸代谢以及血液循环能促进了受损神经细胞的再生以及增强了神经元存活能力。并且鸟氨酸和天冬氨酸可以刺激肝尿素循环活性,通过尿素循环可将氨基酸代谢过程中产生的大量的氨排出体外。生物体内无论是神经调节还是激素调节,最终都是通过酶起作用。所以本发明中添加的大剂量维生素B6为人体氨基酸代谢、神经递质γ-氨基丁酸(GABA)和谷氨酸(Glu)的提供了充足的辅酶。虽然运动神经元病患者脑脊液中的谷氨酸水平偏高,但是使用本发明后,脑脊液中的谷氨酸可以转化为谷氨酰胺和谷胱甘肽。①人体通过谷氨酰胺可以从脑、肌肉等组织向肝或肾转运氨。谷氨酰胺没有毒性,是人体迅速解除氨毒的一种方式,在本病中也是迅速解除胞外过高的谷氨酸浓度对中枢神经***产生的明显毒性作用,同时储藏和运输氨。当运至肝脏中,谷氨酰胺将氨释放出来以合成尿素;当运至肾脏中,谷氨酰胺将氨释放出来直接随尿排出;运至各种组织中可用于合成氨基酸和嘌呤、嘧啶等含氮物质。也就是说本发明可以促进谷氨酰胺的合成,解除胞外过高的谷氨酸浓度对中枢神经***产生的明显毒性作用,并且谷氨酰胺能直接通过血脑屏障,为脑神经细胞的修复提供部分氨基酸、嘌呤和嘧啶。②谷胱甘肽的合成可以有效的清除体内的自由基,减轻运动神经元病患者的症状。且本发明中的氨基酸也为神经营养因子提供能量以及原料,修复受损的神经细胞。虽然在此过程中氨基酸代谢产生的大量氨,但是由于L-鸟氨酸的存在,L-鸟氨酸作为尿素循环的反应底物,迅速激活肝细胞内的尿素循环,将机体产生的有害氨通过尿素排除体外,保证了机体正常的代谢。由于本发明中含有天冬氨酸,其是多种氨基酸及嘌呤、嘧啶碱基的合成前体,并且它对细胞亲和力很强,可作为钾、镁离子载体,向心肌输送电解质,促进细胞去极化,维持心肌收缩能力。其不但可以为神经营养因子提供能量以及原料,修复受损的神经细胞,而且可以促进K+进入神经元细胞,维持心肌收缩能力。并且和L-鸟氨酸联合使用,可以刺激肝尿素循环活性大大增强肝脏排毒功能,迅速降低血氨,促进肝细胞自身的修复和再生,从而增强了人体自身免疫能力,从本质上治疗运动神经元病,且本发明没任何毒副作用、治疗费用低,是运动神经元病患者首选药物。
本发明的有益效果:
本发明提供的组合物能够缓解甚至逆转运动神经元病的发病过程,基本上能够改善运动神经元病患者的临床症状,甚至能正常生活,具有较好的治疗效果,而且该组合物原料为食源性物质,长期服用没有毒副作用,治疗费用低,对运动神经元病患者来说基本没有经济负担,适合临床推广使用。
附图说明
图1是病例1入院时照片,需要无创呼吸机维持呼吸,8个月体重减轻20.5公斤。
图2是病例1入院治疗20天时照片,治疗效果明显行走自如。
图3是病例1肌电图报告单。
图4是病例2入院时照片;左上肢不能活动四肢乏力呛咳两年入院。
图5是病例2新疗法治疗15天时照片;已能够行走3公里效果明显。
图6是病例3入院时照片;患者入院时右上胶不能活动,头部颈部强直。
图7是病例3在北大第三医院确诊ALS诊断证明书。
图8是病例3新疗法治疗15天后照片;右上肢体活动自如,头部颈部活动自如。
图9是病例4入院时照片;检查四肢进行性乏力肌肉震颤。
图10是病例4治疗后照片;治疗效果明显。
图11是病例4肌电图报告单。
图12是病例5入院时照片;检查双下肢已经瘫痪无反射。
图13是病例5经治疗后已能够站立的照片。
图14是病例5肌电图报告单。
具体实施方式
以下通过实施例对本发明作进一步的阐述。
一、药物组合物制备例
实施例1:
一种药物组合物,将相当于L-鸟氨酸2.5g的L-鸟氨酸盐酸盐,天冬氨酸1.5g以及维生素B610g,加入到5%葡萄糖氯化钠注射液1000mL中即可。
实施例2:
一种药物组合物,其组分为复方氨基酸注射液1000mL(含有:相当于L-鸟氨酸3.5g的L-鸟氨酸盐酸盐,天冬氨酸2.50g,精氨酸8.80g,异亮氨酸8.80g,亮氨酸13.60g,相当于赖氨酸7.51g的赖氨酸醋酸盐,蛋氨酸1.20g,苯丙氨酸1.60g,苏氨酸4.60g,色氨酸1.50g,缬氨酸10.60g,组氨酸4.70g,甘氨酸6.30g,丙氨酸8.30g,脯氨酸7.10g,天冬酰胺0.55g,相当于半胱氨酸0.60g的N-乙酰-L-半胱氨酸,谷氨酸5.70g,丝氨酸3.70g,相当于酪氨酸0.70g的N-乙酰-L-酪氨酸),以及维生素B616g和维生素C 3g,维生素加入到0.9%氯化钠注射液500mL中。
实施例3:
一种药物组合物,其组分为复方氨基酸注射液1000mL(含有:相当于L-鸟氨酸4.5g的L-鸟氨酸盐酸盐,天冬氨酸2.80g,精氨酸8.30g,异亮氨酸6.50g,亮氨酸12.00g,相当于赖氨酸7.51g的赖氨酸醋酸盐,蛋氨酸1.60g,苯丙氨酸1.40g,色氨酸1.80g,缬氨酸10.60g,组氨酸4.80g,甘氨酸6.20g,丙氨酸8.50g,脯氨酸7.10g,天冬酰胺0.55g,谷氨酸5.70g,丝氨酸3.70g,相当于酪氨酸0.70g的N-乙酰-L-酪氨酸),以及维生素B610g,维生素B13mg,维生素B23mg,维生素B340mg,泛酸8mg,生物素0.4mg,叶酸0.6mg,维生素B1210μg;维生素C 4g。
维生素可直接加入到复方氨基酸注射液中,或者加入到5%葡萄糖氯化钠注射液中。如果是糖尿病患者,则可将维生素加入到0.9%氯化钠注射液中。
实施例4:
一种药物组合物,其组分为复方氨基酸注射液1000mL(含有:异亮氨酸8.80g,亮氨酸13.60g,赖氨酸醋酸盐10.60g(相当于赖氨酸7.51g),蛋氨酸1.20g,苯丙氨酸1.60g,苏氨酸4.60g,色氨酸1.50g,缬氨酸10.60g,精氨酸8.80g,组氨酸4.70g,甘氨酸6.30g,丙氨酸8.30g,脯氨酸7.10g,天冬氨酸2.50g,天冬酰胺0.55g,N-乙酰-L-半胱氨酸0.80g(相当于半胱氨酸0.60g),谷氨酸5.70g,L-鸟氨酸盐酸盐1.66g(相当于L-鸟氨酸1.30g),丝氨酸3.70g,N-乙酰-L-酪氨酸0.86g(相当于酪氨酸0.70g)),以及维生素B610g。
维生素可直接加入到复方氨基酸注射液中,或者加入到5%葡萄糖氯化钠注射液中。如果是糖尿病患者,则可将维生素加入到0.9%氯化钠注射液中。
实施例5:
一种药物组合物,其组分为复方氨基酸注射液1000mL(含有:异亮氨酸8.80g,亮氨酸13.60g,赖氨酸醋酸盐10.60g(相当于赖氨酸7.51g),蛋氨酸1.20g,苯丙氨酸1.60g,苏氨酸4.60g,色氨酸1.50g,缬氨酸10.60g,精氨酸8.80g,组氨酸4.70g,甘氨酸6.30g,丙氨酸8.30g,脯氨酸7.10g,天冬氨酸2.50g,天冬酰胺0.55g,N-乙酰-L-半胱氨酸0.80g(相当于半胱氨酸0.60g),谷氨酸5.70g,L-鸟氨酸盐酸盐1.66g(相当于L-鸟氨酸1.30g),丝氨酸3.70g,N-乙酰-L-酪氨酸0.86g(相当于酪氨酸0.70g)),以及维生素B610g和维生素C 4g。
维生素可直接加入到复方氨基酸注射液中,或者加入到5%葡萄糖氯化钠注射液中。如果是糖尿病患者,则可将维生素加入到0.9%氯化钠注射液中。
实施例6:
一种药物组合物,其组分为复方氨基酸注射液1000mL(含有:异亮氨酸8.80g,亮氨酸13.60g,赖氨酸醋酸盐10.60g(相当于赖氨酸7.51g),蛋氨酸1.20g,苯丙氨酸1.60g,苏氨酸4.60g,色氨酸1.50g,缬氨酸10.60g,精氨酸8.80g,组氨酸4.70g,甘氨酸6.30g,丙氨酸8.30g,脯氨酸7.10g,天冬氨酸2.50g,天冬酰胺0.55g,N-乙酰-L-半胱氨酸0.80g(相当于半胱氨酸0.60g),谷氨酸5.70g,L-鸟氨酸盐酸盐1.66g(相当于L-鸟氨酸1.30g),丝氨酸3.70g,N-乙酰-L-酪氨酸0.86g(相当于酪氨酸0.70g)),以及维生素B620g和维生素C 6g。
维生素可直接加入到复方氨基酸注射液中,或者加入到5%葡萄糖氯化钠注射液中。如果是糖尿病患者,则可将维生素加入到0.9%氯化钠注射液中。
实施例7:
一种保健品口服液,其组分为复方氨基酸口服液1000mL(含有:异亮氨酸8.80g,亮氨酸13.60g,赖氨酸醋酸盐10.60g(相当于赖氨酸7.51g),蛋氨酸1.20g,苯丙氨酸1.60g,苏氨酸4.60g,色氨酸1.50g,缬氨酸10.60g,精氨酸8.80g,组氨酸4.70g,甘氨酸6.30g,丙氨酸8.30g,脯氨酸7.10g,天冬氨酸2.50g,天冬酰胺0.55g,N-乙酰-L-半胱氨酸0.80g(相当于半胱氨酸0.60g),谷氨酸5.70g,L-鸟氨酸盐酸盐1.66g(相当于L-鸟氨酸1.30g),丝氨酸3.70g,N-乙酰-L-酪氨酸0.86g(相当于酪氨酸0.70g)),以及维生素B610g和维生素C 4g。维生素可直接加入到复方氨基酸口服液中,也可以分别包装,一起服用。
二、临床治疗实施例
本院已收治运动神经元病患者十多例,采用“复方氨基酸联用大剂量维生素B6新疗法”治疗均取得了较好的治疗效果,现摘录部分病例如下:
病例1:
住院号201538307。患者杨某某,男,70岁,江苏省常州市人。因进行性言语不清,呼吸困难,吞咽困难,消瘦,乏力一年于2015年4月28日入院治疗。患者一年前无明显诱因出现言语不清,口干,消瘦,开始为手部上肢肌肉消瘦明显,并进行性加重,感觉肉跳,双手麻木。逐步全身肌肉萎缩。伴逐步乏力,不能爬楼梯。饮水有呛咳,气喘,夜间平卧后胸闷气急明显,无胸痛。患者肌电图测定报告,运动神经元损害肌电图改变,累及上下肢体和腹直肌以口腔部位肌肉、斜方肌等。脊髓前角细胞损害。患者先后到多个大医院去诊断及治疗,在上海华山医院等医院确诊为运动神经元病(渐冻人症,肌萎缩侧索硬化症,amyotrophic lateral sclerosis,ALS)。予营养神经,“利鲁唑”一片,一天两次,但患者症状一天一天加重,呼吸愈来愈困难,近8个月来,体重减轻20.5公斤。今日患者要求住院,要求对症治疗。近期患者感乏力加重,气喘明显,白天及夜间需要无创呼吸机辅助呼吸。无抽搐,无发热咳嗽,夜眠食欲差,感尿频,尿急,无血尿。大便困难。入院立即给以复方氨基酸联用维生素B6新疗法治疗。处方具体如下:复方氨基酸注射液500ml/日,静滴,1次/日;5%GNS 250ml+维生素B63g+维生素C 2g,每日1次,静滴,连续使用直致病情控制,患者连续用药5天后,临床症状好转,呼吸急促症状减轻,吞咽困难明显好转,连续用药15天后,患者口干、消瘦、感觉肉跳、双手麻木、全身肌肉萎缩、乏力、饮水呛咳、气喘等症状都有十分明显好转,双上肢近端肌力、双下肢肌力明显增加,可以自由行走,能够在家阳台上浇花等。12月1日患者继续用新疗法输注一周后,呛咳气喘好转,视物模糊好转。夜间睡眠差。查体:神清,精神可,两肺呼吸音粗,未及明显干湿性啰音,腹平软,无压痛。舌肌萎缩,纤颤,双手骨间肌,四肢肌肉萎缩,双手握力IV-级,双上肢近端肌力V-级,双下肢肌肉V-级,脑脊液中谷氨酸含量测定较入院时降低(腰椎穿刺术,下同),患者发病后两次肺功能测定未能成功,本次出院前肺功能测定基本正常。
治疗前T淋巴细胞亚群检测(2015-12-1):
CD3:80.01(61.10-77.0%);CD4:47.12(25.80-41.60%);
CD8:30.41(18.10-29.60%);CD4/CD8:1.55(0.71-2.78);
NK细胞:8.21(8.10-35.60%);B淋巴细胞:10.80(5-18.0%)。
治疗后T淋巴细胞亚群检测(2015-12-9):
CD3:74.70(61.10-77.0%);CD4:45.15(25.80-41.60%);
CD8:30.28(18.10-29.60%);CD4/CD8:1.36(0.71-2.78);
NK细胞:9.53(8.10-35.60%);B淋巴细胞:13.97(5-18.0%)。
通过对比治疗前后的T淋巴细胞亚群检测结果可以发现,患者的免疫功能也得到了改善。
注:T淋巴细胞亚群检测报告单中括号内数值为正常参考值,下同。
患者治疗后效果明显,治疗到现在已经8个月,病情没有恶化,好转明显。
病例2:
住院号201529588。患者刘某,男,52岁,贵州遵义人。因“进行性四肢乏力,呛咳两年”于2015-9-14入院。患者有进行性四肢乏力,呛咳两年病史。开始为左手不自主抽动,乏力,伴左侧手部上肢肌肉消瘦明显,并进行性加重,半年后逐步出现四肢乏力,抽动。能平地慢行,易跌倒。饮水有呛咳,讲话费力,含糊。近期症状加重,家族中无类似病史,既往体健。在上海华山医院肌电图已确诊为渐冻人症(肌萎缩侧索硬化症,amyotrophic lateral sclerosis,ALS)。体格检查:T 36.2℃,P 70次/分,R 17次/分,BP 128/80mmHg。神志清醒,发育正常,营养良好,正常面容,体型适中,步入病房,自主***,对答切题,查体合作。皮肤粘膜无黄染,无肝掌,无蜘蛛痣,无贫血貌。全身浅表***无肿大。无巩膜黄染,***红润。颈软,颈静脉无怒张,肝颈静脉回流征未做,双侧甲状腺无肿大。双肺呼吸音清,未及干啰音、湿啰音。心率70次/分,心律齐,无病理性杂音。腹壁柔软,无压痛,无反跳痛,肝肋下未触及,脾肋下未触及,未触及腹部包块。无肝区叩击痛,无肾区叩击痛,移动性浊音(-)。双下肢无浮肿。生理反射存在。舌肌萎缩,纤颤,双手骨间肌,四肢肌肉萎缩,左手握力I级,左上肢近端肌力III级,右手握力IV级,右上肢近端肌力IV级,双下肢肌肉IV级,巴彬斯基征阳性,腱反射无亢进。处方具体如下:复方氨基酸注射液500ml/日,静滴,1次/日;5%GNS 250ml+维生素B63g+维生素C2g,每日1次,静滴,连续使用直致病情控制,患者治疗2周后患者入院时只能行走200米,目前自己能行走两公里,乏力症状好转。查体:神清,咽部不红,两肺呼吸音粗,无啰音,腹平软,无压痛,肠鸣音低。舌肌萎缩,纤颤,双手骨间肌,四肢肌肉萎缩,左手握力I级,左上肢近端肌力III级,右手握力IV级,右上肢近端肌力IV级,双下肢肌肉IV级,腱反射无亢进。
治疗前T淋巴细胞亚群检测(2015-9-15):
CD3:74.36(61.10-77.0%);CD4:48.71(25.80-41.60%);
CD8:20.57(18.10-29.60%);CD4/CD8:2.37(0.71-2.78);
NK细胞:4.34(8.10-35.60%);B淋巴细胞:20.68(5-18.0%)。
治疗后T淋巴细胞亚群检测(2015-9-29):
CD3:71.74(61.10-77.0%);CD4:39.35(25.80-41.60%);
CD8:22.98(18.10-29.60%);CD4/CD8:1.71(0.71-2.78);
NK细胞:11.85(8.10-35.60%);B淋巴细胞:15.23(5-18.0%)。
通过对比治疗前后的T淋巴细胞亚群检测结果可以发现,患者的免疫功能也得到了改善。
患者治疗后病情没有恶化,好转明显。
病例3:
住院号201535047。患者郝某某,男,60岁,北京人。因“进行性双上肢乏力伴肌萎缩二年余”于2015年11月3日,步入病房。患者,老年男性,于2013年8月右肩部外伤后,出现右上肢乏力,进而发展为双上肢乏力伴右上肢肌肉萎缩,并进行性加重,于北京大学第一附属医院行肌电图报告提示:右母短展肌、双肱二头肌、右胸锁乳突肌呈神经源性损害;左小指展肌、T10脊旁肌轻收缩运动单位电位时限正常波幅增高。在北医三院确诊渐冻人症(肌萎缩侧索硬化症,amyotrophic lateral sclerosis,ALS)。曾于多家医院就诊行神经保护、干细胞移植、中药治疗、针灸推拿等对症支持治疗(具体不祥),但疗效不显著。目前患者感双上肢乏力加重,抬头无力,伴有右上臂肌萎缩及肩胛上部肌萎缩,双下肢无明显乏力感,无呼吸困难、呛咳。体格检查:T 36.4℃,P 80次/分,R 17次/分,BP125/85mmHg。神志清醒,发育正常,营养中等,正常面容,体型偏瘦,步入病房,自主***,对答切题,查体合作。皮肤粘膜无黄染,无肝掌,无蜘蛛痣,无贫血貌。全身浅表***无肿大。无巩膜黄染,***红润。颈软,颈静脉无怒张,肝颈静脉回流征未做,双侧甲状腺无肿大。双肺呼吸音清,未及干啰音、湿啰音。心率80次/分,心律齐,无病理性杂音。腹壁柔软,无压痛,无反跳痛,肝肋下未触及,脾肋下未触及,未触及腹部包块。无肝区叩击痛,无肾区叩击痛,移动性浊音(-)。舌肌纤颤、无萎缩。转颈及抬头无力。耸肩无力。双上肢及肩部肌肉萎缩。双侧三角肌肌力肌力Ⅲ-级。肱二头肌肌力III级,双侧骨间肌萎缩,握力稍减弱.双下肢肌力正常。双下肢无水肿。双下肢活动自如、肌力正常,双下肢无浮肿。生理反射存在余病理反射未引出。处方具体如下:复方氨基酸注射液500ml/日,静滴,1次/日;5%GNS 250ml+维生素B65g+维生素C 2g,每日1次,静滴,连续使用直致病情控制,十天后诉右小指能并拢,患者自觉肩部不适好转,右肩部较前活动度好转。大小便正常。查体:神清,心肺阴性,腹平软,无压痛,肠鸣音低。舌肌纤颤、无萎缩。转颈及抬头无力。耸肩无力。双上肢及肩部肌肉萎缩。双侧三角肌肌力肌力Ⅲ-级。肱二头肌肌力III级,双侧骨间肌萎缩,握力稍减弱,双下肢肌力正常。脑脊液中谷氨酸含量测定较入院时降低。
治疗前T淋巴细胞亚群检测(2015-11-4):
CD3:80.47(61.10-77.0%);CD4:61.67(25.80-41.60%);
CD8:16.21(18.10-29.60%);CD4/CD8:3.80(0.71-2.78);
NK细胞:8.97(8.10-35.60%);B淋巴细胞:8.83(5-18.0%)。
治疗后T淋巴细胞亚群检测(2015-11-4):
CD3:79.61(61.10-77.0%);CD4:59.56(25.80-41.60%);
CD8:17.67(18.10-29.60%);CD4/CD8:3.37(0.71-2.78);
NK细胞:13.97(8.10-35.60%);B淋巴细胞:5.75(5-18.0%)。
通过对比治疗前后的T淋巴细胞亚群检测结果可以发现,患者的免疫功能也得到了改善。
患者治疗后效果比较明显。
病例4:
住院号201535276。患者虞某某,男,41岁,江苏省常州市人。因“四肢进行性乏力,言语含糊8年”于2015-11-05步入病房。患者,中年男性,8年前无明显诱因出现下肢乏力,走路不稳,上楼梯费劲,左侧明显,无麻木,无疼痛。伴讲话含糊。3年前出现双上肢乏力,手部肌肉消瘦,手指不能并拢,不能抬物,并进行性加重,感觉肉跳,双手麻木,逐步乏力加重。抬头无力,饮水有时呛咳,活动后气喘。在上海,南京多家医院神经内科就诊,肌电图示神经源性病变,确诊(渐冻人症,肌萎缩侧索硬化症,amyotrophic lateralsclerosis,ALS)。,治疗效果不好。平时有血压偏高史。3.体格检查:T 37℃,P 80次/分,R 17次/分,BP 126/90mmHg。神志清醒,发育正常,营养良好,慢性病面容,体型适中,步入病房,自主***,对答切题,查体合作。皮肤粘膜无黄染,无肝掌,无蜘蛛痣,无贫血貌。全身浅表***无肿大。无巩膜黄染,***红润。颈软,颈静脉无怒张,肝颈静脉回流征未做,双侧甲状腺无肿大。双肺呼吸音清,未及干啰音、湿啰音。心率80次/分,心律齐,无病理性杂音。腹壁柔软,无压痛,无反跳痛,肝肋下未触及,脾肋下未触及,未触及腹部包块。无肝区叩击痛,无肾区叩击痛,移动性浊音(-)。四肢活动自如,双下肢无浮肿。伸舌居中,舌肌萎缩,纤颤,双手骨间肌,四肢肌肉萎缩。双上肢近端肌力III级,双手手握力IV级,双下肢肌肉IV级,肌张力不高。四肢感觉存在,膝反射减弱,巴彬斯基征阴性。4.实验室和器械检查:肌电图(2015-5-4):神经源性损害肌电改变,累及上下肢和腹直肌,以及斜方肌和胸锁乳突肌,舌肌轻度损害改变。脊髓前角细胞和舌下神经运动核损害首先考虑。处方具体如下。复方氨基酸注射液500ml/日,静滴,1次/日;5%GNS 250ml+维生素B65g+维生素C 2g,每日1次,静滴,连续使用直致病情控制,患者经治疗两周后感肩部较前有力,双肩能抬过头部,有所好转。查体:神清,心肺阴性,腹平软,无压痛,肠鸣音低。伸舌居中,舌肌萎缩,纤颤,双手骨间肌,四肢肌肉萎缩。双上肢近端肌力III级,双手手握力IV级,双下肢肌肉IV级,肌张力不高。四肢感觉存在,膝反射减弱,脑脊液中谷氨酸含量测定较入院时降低。
治疗前T淋巴细胞亚群检测(2015-11-6):
CD3:62.79(61.10-77.0%);CD4:37.91(25.80-41.60%);
CD8:23.88(18.10-29.60%);CD4/CD8:1.59(0.71-2.78);
NK细胞:16.33(8.10-35.60%);B淋巴细胞:17.23(5-18.0%)。
治疗后T淋巴细胞亚群检测(2015-11-18):
CD3:72.08(61.10-77.0%);CD4:43.62(25.80-41.60%);
CD8:26.91(18.10-29.60%);CD4/CD8:1.62(0.71-2.78);
NK细胞:18.81(8.10-35.60%);B淋巴细胞:7.83(5-18.0%)。
通过对比治疗前后的T淋巴细胞亚群检测结果可以发现,患者的免疫功能也得到了改善。
患者经过治疗后,效果比较明显。
病例5:
住院号201536413。患者黄某某,男,52岁,江西省南昌人。因“进行性四肢无力一年余”于2015年11月13日入院。
患者中年男性,一年前无明显诱因下出现双下肢无力,阵发性抽搐,疼痛。休息后无明显缓解,并逐渐加重,开始出现不能自行行走,双下肢不能活动,只能坐在轮椅上,双下肢已瘫痪。至上海北京等医院就诊,在北医三院确诊(渐冻人症,肌萎缩侧索硬化症,amyotrophic lateral sclerosis ALS),予以保守治疗后效果欠佳并逐渐加重,开始出现双上肢乏力症状,无吞咽困难,无呛咳。无呼吸困难。家属中无类似疾病。体格检查:T 37℃,P 80次/分,R 17次/分,BP 130/80mmHg。神志清醒,发育正常,营养中等,慢性病面容,体型适中,推车入病房,被动***,对答切题,查体合作。皮肤粘膜无黄染,无肝掌,无蜘蛛痣,无贫血貌。全身浅表***无肿大。无巩膜黄染,***红润。颈软,颈静脉无怒张,肝颈静脉回流征未做,双侧甲状腺无肿大。双肺呼吸音清,未及干啰音、湿啰音。心率80次/分,心律齐,无病理性杂音。腹壁柔软,无压痛,无反跳痛,肝肋下未触及,脾肋下未触及,未触及腹部包块。无肝区叩击痛,无肾区叩击痛,移动性浊音(-)。脊柱无畸形。舌肌纤颤、无萎缩。耸肩无力。肩部肌肉,双下肢均匀性萎缩。双侧上肢肌力V-,肌张力正常,双手骨间肌无萎缩,握力稍减弱,肌张力好。双下肢肌力0级,无肌张力,双下肢无水肿。膝反射无,病理征阴性,浅感觉存在,深感觉减弱。腰肌力量减弱。实验室和器械检查:肌电图(上海华山医院,2014-8-14)神经源性损害肌电改变,累及上下肢和腹直肌以及斜方肌和胸锁乳突肌。脊髓前角细胞损害可首先考虑。
处方具体如下。复方氨基酸注射液500ml/日,静滴,1次/日;5%GNS 250ml+维生素B65g+维生素C 2g,每日1次,静滴,连续使用直致病情控制,患者入院十天后。查体:神清,心肺阴性,腹平软,无压痛,肠鸣音低。耸肩无力。肩部肌肉,双下肢均匀性萎缩。双侧上肢肌力V-,肌张力正常,双手骨间肌无萎缩,握力稍减弱,肌张力好。双下肢肌力0级,足部肌肉有收缩。肌张力较入院有增强,双下肢无水肿。膝反射无,病理征阴性,浅感觉存在,深感觉减弱。目前患者已经能够自行站立6分钟了,双下肢肌肉的肌力和肌肉营养比较治疗前明显改善,治疗效果比较明显。
治疗前T淋巴细胞亚群检测(2015-11-14):
CD3:78.87(61.10-77.0%);CD4:52.38(25.80-41.60%);
CD8:22.85(18.10-29.60%);CD4/CD8:2.29(0.71-2.78);
NK细胞:9.68(8.10-35.60%);B淋巴细胞:9.04(5-18.0%)。
治疗后T淋巴细胞亚群检测(2015-11-27):
CD3:69.28(61.10-77.0%);CD4:41.16(25.80-41.60%);
CD8:24.73(18.10-29.60%);CD4/CD8:1.66(0.71-2.78);
NK细胞:22.75(8.10-35.60%);B淋巴细胞:7.06(5-18.0%)。
通过对比治疗前后的T淋巴细胞亚群检测结果可以发现,患者的免疫功能也得到了改善。
患者治疗后病情没有恶化,好转明显。
注:上述病例1-5中采用的复方氨基酸注射液,每1000mL中含有:异亮氨酸8.80g,亮氨酸13.60g,赖氨酸醋酸盐10.60g(相当于赖氨酸7.51g),蛋氨酸1.20g,苯丙氨酸1.60g,苏氨酸4.60g,色氨酸1.50g,缬氨酸10.60g,精氨酸8.80g,组氨酸4.70g,甘氨酸6.30g,丙氨酸8.30g,脯氨酸7.10g,天冬氨酸2.50g,天冬酰胺0.55g,N-乙酰-L-半胱氨酸0.80g(相当于半胱氨酸0.60g),谷氨酸5.70g,L-鸟氨酸盐酸盐1.66g(相当于L-鸟氨酸1.30g),丝氨酸3.70g,N-乙酰-L-酪氨酸0.86g(相当于酪氨酸0.70g)。
Claims (10)
1.一种用于治疗运动神经元病的组合物,其特征是每单位该组合物中含有:相当于L-鸟氨酸含量为0.5~8g的L-鸟氨酸盐,天冬氨酸1~5g,维生素B66-20g。
2.根据权利要求1所述的组合物,其特征在于每单位该组合物中还含有下列物质中的一种或多种:精氨酸,异亮氨酸,亮氨酸,赖氨酸,蛋氨酸,苯丙氨酸,苏氨酸,色氨酸,缬氨酸,组氨酸,甘氨酸,丙氨酸,脯氨酸,天冬酰胺,半胱氨酸,谷氨酸,丝氨酸,酪氨酸,维生素B1,维生素B2,维生素B3,泛酸,生物素,叶酸,维生素B12,维生素C;
上述氨基酸可以采用氨基酸的各种可溶性盐或者其衍生物。
3.根据权利要求2所述的组合物,其特征在于赖氨酸采用赖氨酸醋酸盐,半胱氨酸采用N-乙酰-L-半胱氨酸,酪氨酸采用N-乙酰-L-酪氨酸;
各氨基酸的用量分别是:精氨酸3~10g,异亮氨酸3~10g,亮氨酸5~15g,相当于赖氨酸含量为3~10g的赖氨酸醋酸盐,蛋氨酸0.5~3g,苯丙氨酸0.5~3g,苏氨酸3~10g,色氨酸0.5~3g,缬氨酸5~15g,组氨酸3~8g,甘氨酸3~8g,丙氨酸3~10g,脯氨酸3~8g,天冬酰胺0.1~3g,相当于半胱氨酸含量为0.1~3g的N-乙酰-L-半胱氨酸,谷氨酸3~10g,丝氨酸0.5~5g,相当于酪氨酸含量为0.1~3g的N-乙酰-L-酪氨酸;
维生素的用量分别是:维生素B12~4mg,维生素B22~4mg,维生素B320~40mg,泛酸6~10mg,生物素0.2~0.4mg,叶酸0.2~0.8mg,维生素B124~12μg;维生素C 2-6g。
4.根据权利要求3所述的组合物,其特征在于每单位该组合物中含有:
异亮氨酸8.80g,亮氨酸13.60g,赖氨酸醋酸盐10.60g,蛋氨酸1.20g,苯丙氨酸1.60g,苏氨酸4.60g,色氨酸1.50g,缬氨酸10.60g,精氨酸8.80g,组氨酸4.70g,甘氨酸6.30g,丙氨酸8.30g,脯氨酸7.10g,天冬氨酸2.50g,天冬酰胺0.55g,N-乙酰-L-半胱氨酸0.80g,谷氨酸5.70g,L-鸟氨酸盐酸盐1.66g,丝氨酸3.70g,N-乙酰-L-酪氨酸0.86g,维生素B610g。
5.根据权利要求4所述的组合物,其特征在于每单位该组合物中还含有维生素C 4g。
6.根据权利要求1-5所述的任一组合物,其特征在于该组合物还含有适量的5%葡萄糖氯化钠注射液或0.9%氯化钠注射液。
7.根据权利要求1-5所述的任一组合物,其特征在于该组合物的剂型为药学上允许的任意剂型或保健品允许的任意剂型。
8.根据权利要求7所述的任一组合物,其特征在于该组合物的剂型为注射剂、口服液、片剂、颗粒剂、胶囊剂、冲剂。
9.权利要求1-5所述的任一组合物在制备治疗运动神经元病的药物或保健品中的应用。
10.一种治疗运动神经元病的方法,其特征在于该方法采用注射或口服的方式给予患者权利要求1-5所述的组合物;所述注射方式优选静脉注射。
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WO2020064946A3 (en) * | 2018-09-27 | 2020-05-07 | Société des Produits Nestlé S.A. | Compositions and methods using at least one glycine or derivative thereof, at least one n-acetylcysteine or derivative thereof, and at least one nicotinamide riboside or nad+ precursor |
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