CN116650482A - 3-typ在制备治疗自身免疫性脱髓鞘疾病药物中的应用 - Google Patents
3-typ在制备治疗自身免疫性脱髓鞘疾病药物中的应用 Download PDFInfo
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- CN116650482A CN116650482A CN202210147087.XA CN202210147087A CN116650482A CN 116650482 A CN116650482 A CN 116650482A CN 202210147087 A CN202210147087 A CN 202210147087A CN 116650482 A CN116650482 A CN 116650482A
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Abstract
本发明属于医药技术领域,公开了式(I)所示的3‑TYP在制备预防、缓解和/或治疗自身免疫性脱髓鞘疾病中的应用。在小鼠实验性自身免疫性脑脊髓炎模型上,3‑TYP显示了很好的治疗作用,其可有效地治疗疾病的病理变化和疾病的进展。其治疗作用是通过减轻脊髓炎症细胞浸润和减少脊髓髓鞘脱失实现,其减轻脊髓炎症,抑制促炎因子生成可能通过调节M1/M2型小胶质细胞极化状态实现。
Description
技术领域
本发明涉及3-TYP在制备预防、缓解和/或治疗自身免疫性脱髓鞘疾病药物中的应用,属于医药技术领域。
背景技术
多发性硬化(multiple sclerosis,MS)是一种由免疫介导的慢性进行性中枢神经系统(central nervous system,CNS)炎症性脱髓鞘疾病。全世界有超过200多万人受累,它对人类身体健康造成严重危害,并给社会造成沉重的经济负担。多发性硬化的发病机制复杂,病因不明,目前不能治愈,患者需接受长期治疗。多发性硬化以炎症和大脑、脊髓和视神经出现脱髓鞘病变为主要病理特征,其临床表现广泛,包括肌肉无力、感觉障碍、认知功能障碍和疲劳等。多发性硬化的病因尚不明确,可能与遗传、环境、感染等多种因素相关。根据患者的临床表现,多发性硬化症可分为四种类型:复发缓解型,表现为复发缓解交替,病情无明显进展;原发进展型,即起病后不断恶化;继发进展型,以复发缓解型起病继以不断恶化;进展复发型,发病后病情逐渐进展伴有复发。目前,临床上的治疗药物多针对复发缓解型病人。
多发性硬化被认为是一种自身免疫性疾病,主要由自身反应性免疫细胞通过血脑屏障进入CNS导致。其早期病变表现为周围免疫细胞浸润和血脑屏障(blood brainbarrier,BBB)渗漏。细胞浸润以巨噬细胞为主,CD8+T细胞次之,CD4+T细胞、B细胞和浆细胞数量相对较少。T细胞的组成并未随疾病的发展而改变,但B细胞和浆细胞的相对比例增加。小胶质细胞和巨噬细胞在整个疾病过程中保持慢性启动的状态,形成髓鞘和少突胶质细胞丢失的斑块。随疾病进展,患者大脑出现局灶性白质病变,大脑和脊髓损伤不明显,但脑萎缩普遍出现,脑萎缩伴随脑室增大,星形胶质细胞在白质病变中形成多发硬化性胶质瘢痕,在大脑皮质、核和脊髓的灰质中也会发生脱髓鞘,但白质的脱髓鞘区域可以通过髓鞘再生得到部分修复;此外,疾病过程不仅影响髓磷脂,还会导致轴突和神经元出现退行性病变,从而造成患者出现不可逆转的残疾。
过去二十多年,随着人们对多发性硬化症发病机制认识的不断深入,研究人员开发出了多种针对该疾病特殊生理途径的药物。目前,用于治疗多发性硬化症的药物主要分为五大类:免疫调节剂、激素类、单克隆抗体、干扰素类和神经修复剂。这些药物可以缓解疾病进展,控制患者的症状,但对于修复受损神经元无效,对患者的功能型残疾无改善作用,且长期应用有严重的毒副作用。
实验性自身免疫性脑脊髓炎(experimentally allergic encephalomyelitis,EAE)模型是一种经典的多发性硬化动物模型,由髓鞘自身抗原特异性启动脑部辅助T细胞,使中枢神经系统发生炎性浸润,髓鞘脱失,其生化、免疫及病理特征都与多发性硬化症非常相似。此外,大鼠及小鼠EAE还可作为研究实验性自身免疫性脑脊髓炎、视神经脑脊髓炎和急性播散性脑脊髓炎等自身免疫性脱髓鞘疾病的理想动物模型,其在临床、病理、免疫及生化改变等方面都与人类脱髓鞘疾病较为相似,因此应用广泛。
3-TYP(3-(1氢-1,2,3-三唑-4-基)吡啶)是一种选择性的Sirt3抑制剂,相对于Sirt1和Sirt2来说,其对Sirt3具有较高选择性。已有研究显示,3-TYP可抑制线粒体自噬并减轻高糖加重的神经元缺氧再灌注损伤,证实了3-TYP具有潜在的药理活性。
本发明为经过大量动物实验研究获得的新发现。新的发明内容主要涉及为临床提供治疗自身免疫性脱髓鞘疾病的药物。目前有关3-TYP在自身免疫性脱髓鞘疾病的直接或间接治疗作用尚无相关报导。
迄今为止,未有专利涉及有关3-TYP的药理作用,亦未见3-TYP对于治疗自身免疫性脱髓鞘疾病的研究报导。因此,本发明所述的3-TYP在制备预防、缓解和/或治疗自身免疫性脱髓鞘疾病药物中的应用是新发现的3-TYP的新用途。
发明内容
本发明要解决的技术问题是,提供3-TYP在制备预防、缓解和/或治疗自身免疫性脱髓鞘疾病药物中的应用。
为解决本发明的技术问题,本发明提供如下技术方案:;
本发明技术方案的第一方面是提供了如式(I)所示的3-TYP在制备预防、缓解和/或治疗自身免疫性脱髓鞘疾病药物中的应用,
所述自身免疫性脱髓鞘疾病包括但不局限于中枢神经系统(Central nervoussystem,CNS)的脱髓鞘自身免疫病如多发性硬化症,视神经脊髓炎谱系疾病(Neuromyelitis optica spectrum disorder,NMOSD),急性播散性脑脊髓炎,白质脑炎和横贯性脊髓炎;影响外周神经系统的脱髓鞘自身免疫病如急性炎性脱髓鞘多发性神经病(acute inflammatory demyelinating polyneuropathy,AIDP;吉兰-巴雷综合征),慢性炎性脱髓鞘多发性神经病(chronic inflammatory demyelinating polyneuropathy),抗-MAG周围神经病(anti-MAG peripheral neuropathy),运动与感觉神经病(Motor andSensory Neuropathy,HMSN),遗传学感觉运动神经病(Hereditary SensorimotorNeuropathy,HSMN),腓骨肌萎缩症(Peroneal Muscular Atrophy),进行性神经性腓骨肌萎缩症(Charcot-Marie-Tooth Disease)等。
所述多发性硬化症包括复发缓解型多发性硬化症、原发进展型多发性硬化症、继发进展型多发性硬化症和进展复发型多发性硬化症。
采用雌性C57BL/6小鼠,建立EAE模型。检测3-TYP对动物疾病评分的影响;通过悬挂实验观察动物四肢力量,观察治疗情况。应用H&E染色和LFB染色检测3-TYP对实验动物脊髓内炎性细胞浸润和髓鞘脱失的改善作用。此外,应用qRT-PCR技术检测M1/M2型小胶质细胞标志物和促炎因子的mRNA表达水平,观察3-TYP抗神经炎症的作用。据此判定3-TYP在制备预防、缓解和/或治疗自身免疫性脱髓鞘疾病药物中的作用。
本发明技术方案的第二方面是提供了一种药物组合物在制备预防、缓解和/或治疗自身免疫性脱髓鞘疾病药物中的应用,其特征在于,所述的药物组合物含有有效剂量的如式(I)所示的3-TYP,及药用赋形剂,
其中,所述的药物组合物除含有3-TYP作为药物活性成分外,还含有其他活性成分。所述的药物组合物包括如下的剂型:溶液、混悬液、冻干粉针、乳剂、丸剂、胶囊、粉末、控制释放、持续释放制剂及微粒体给药系统的形式。所述的药用赋形剂包括淀粉、糊精、多甲基纤维素钠、硬脂酸镁、滑石粉。所述的产品选自药品、保健品。
本发明因此还涉及以本发明化合物3-TYP作为活性成份的药物组合物在预防、缓解和/或治疗自身免疫性脱髓鞘疾病药物中的应用。该药物组合物可根据本领域公知的方法制备。可通过将本发明化合物与一种或多种药学上可接受的固体或液体赋形剂和/或辅剂结合,制成适于人或动物使用的任何剂型。
本发明化合物或含有它的药物组合物可以单位剂量形式给药,给药途径可为肠道或非肠道,如口服、静脉注射、肌肉注射、皮下注射、鼻腔、口腔粘膜、眼、肺和呼吸道、皮肤、阴道、直肠等。给药剂型可以是液体剂型、固体剂型或半固体剂型。液体剂型可以是溶液剂(包括真溶液和胶体溶液)、乳剂(包括o/w型、w/o型和复乳)、混悬剂、注射剂(包括水针剂、粉针剂和输液)、滴眼剂、滴鼻剂、洗剂和搽剂等;固体剂型可以是片剂(包括普通片、肠溶片、含片、分散片、咀嚼片、泡腾片、口腔崩解片)、胶囊剂(包括硬胶囊、软胶囊、肠溶胶囊)、颗粒剂、散剂、微丸、滴丸、栓剂、膜剂、贴片、气(粉)雾剂、喷雾剂等;半固体剂型可以是软膏剂、凝胶剂、糊剂等。本发明化合物可以制成普通制剂、也制成是缓释制剂、控释制剂、靶向制剂及各种微粒给药系统。
为了将本发明化合物制成片剂,可以广泛使用本领域公知的各种赋形剂,包括稀释剂、黏合剂、润湿剂、崩解剂、润滑剂、助流剂。稀释剂可以是淀粉、糊精、蔗糖、葡萄糖、乳糖、甘露醇、山梨醇、木糖醇、微晶纤维素、硫酸钙、磷酸氢钙、碳酸钙等;湿润剂可以是水、乙醇、异丙醇等;粘合剂可以是淀粉浆、糊精、糖浆、蜂蜜、葡萄糖溶液、微晶纤维素、阿拉伯胶浆、明胶浆、羧甲基纤维素钠、甲基纤维素、羟丙基甲基纤维素、乙基纤维素、丙烯酸树脂、卡波姆、聚乙烯吡咯烷酮、聚乙二醇等;崩解剂可以是干淀粉、微晶纤维素、低取代羟丙基纤维素、交联聚乙烯吡咯烷酮、交联羧甲基纤维素钠、羧甲基淀粉钠、碳酸氢钠与枸橼酸、聚氧乙烯山梨糖醇脂肪酸酯、十二烷基磺酸钠等;润滑剂和助流剂可以是滑石粉、二氧化硅、硬脂酸盐、酒石酸、液体石蜡、聚乙二醇等。还可以将片剂进一步制成包衣片,例如糖包衣片、薄膜包衣片、肠溶包衣片,或双层片和多层片。为了将给药单元制成胶囊剂,可以将有效成分本发明化合物与稀释剂、助流剂混合,将混合物直接置于硬胶囊或软胶囊中。也可将有效成分本发明化合物先与稀释剂、黏合剂、崩解剂制成颗粒或微丸,再置于硬胶囊或软胶囊中。用于制备本发明化合物片剂的各稀释剂、黏合剂、润湿剂、崩解剂、助流剂品种也可用于制备本发明化合物的胶囊剂。为将本发明化合物制成注射剂,可以用水、乙醇、异丙醇、丙二醇或它们的混合物作溶剂并加入适量本领域常用的增溶剂、助溶剂、pH调剂剂、渗透压调节剂。增溶剂或助溶剂可以是泊洛沙姆、卵磷脂、羟丙基-β-环糊精等;pH调剂剂可以是磷酸盐、醋酸盐、盐酸、氢氧化钠等;渗透压调节剂可以是氯化钠、甘露醇、葡萄糖、磷酸盐、醋酸盐等。如制备冻干粉针剂,还可加入甘露醇、葡萄糖等作为支撑剂。此外,如需要,也可以向药物制剂中添加着色剂、防腐剂、香料、矫味剂或其他添加剂。为达到用药目的,增强治疗效果,本发明的药物或药物组合物可用任何公知的给药方法给药。
有益技术效果
1.本发明的化合物可预防、缓解和/或治疗自身免疫性脱髓鞘疾病。除了拓宽该化合物的临床应用领域,该化合物还为自身免疫性脱髓鞘疾病的临床治疗提供了药物选择。
2.目前在国际和国内,本发明的化合物在预防、缓解和/或治疗自身免疫性脱髓鞘疾病药物中的应用为首次公开。未见相关论文及专利发表。
3.本发明的化合物腹腔注射、少量用药即可达到治疗及预防的效果。药物安全可靠。作为药物进行开发,具有明显的优益。
附图说明
图1. 3-TYP对实验性自身免疫性脑脊髓炎(EAE)小鼠疾病评分的影响。本实验中,发病后EAE模型组小鼠疾病评分显著高于正常对照组,给药后,3-TYP给药组小鼠的疾病评分显著低于EAE模型组,而Sirt3激动剂Honokiol(和厚朴酚,3,5-二-2-丙烯基-1,1-联苯-2,4-二酚)给药组小鼠疾病评分无明显改善。
图2. 3-TYP对EAE小鼠悬挂时间的影响。本实验中,与正常对照组相比,EAE模型组小鼠的在铁丝网上的悬挂时间显著降低,3-TYP可以延长EAE小鼠的悬挂时间,而Honokiol给药组EAE小鼠在铁丝网上的悬挂时间无明显改善。###P<0.001vs.正常对照组,**P<0.01vs.EAE模型组。
图3. 3-TYP对EAE小鼠悬挂分级的影响。##P<0.01,###P<0.001vs.正常对照组;**P<0.01vs.EAE模型组。
图4. 3-TYP对EAE小鼠脊髓炎性细胞浸润的影响。本实验中,与正常对照组相比,EAE模型组小鼠脊髓炎症细胞浸润显著,3-TYP可以显著抑制EAE小鼠脊髓炎性细胞的浸润,而Honokiol给药组EAE小鼠脊髓炎症细胞浸润无明显改善。
图5 3-TYP对EAE小鼠脊髓髓鞘脱失的影响。本实验中,固蓝(Fast blue)/LFB(Luxol Fast Blue)染色后,与正常对照组相比,EAE模型组小鼠脊髓呈现脱髓鞘病灶,面积较大。3-TYP可以使EAE小鼠脊髓白质区域泛白面积减小,有效地改善脱髓鞘情况,而Honokiol给药组EAE小鼠小鼠脊髓白质髓鞘脱失情况无明显改善。
图6 3-TYP对EAE小鼠脊髓促炎因子mRNA水平的影响。本实验中,与正常对照组相比,EAE模型组小鼠脊髓促炎因子TNF-α、IL-6、IL-1β和MCP-1的mRNA水平显著升高,而3-TYP可显著抑制EAE小鼠脊髓促炎因子TNF-α、IL-6、IL-1β和MCP-1的mRNA水平。##P<0.01,###P<0.001vs.正常对照组;*P<0.05,**P<0.01,***P<0.001vs.EAE模型组。
图7 3-TYP对EAE小鼠脊髓M1/M2型小胶质细胞极化的调节。本实验中,3-TYP可抑制EAE小鼠脊髓M1型小胶质细胞标志物CD16、CD32和CD86 mRNA水平的表达,从而抑制EAE小鼠脊髓M1型小胶质细胞极化;且3-TYP可提高M2型小胶质细胞标志物CD206 mRNA水平的表达,促进小胶质细胞向M2型的转换。###P<0.001vs.正常对照组;**P<0.01,***P<0.001vs.EAE模型组。
具体实施方式
下面结合本发明进一步说明3-TYP在预防、缓解和/或治疗自身免疫性脱髓鞘疾病中的药理作用。
下述实施例更详细地举例说明本发明,并不是对本发明的任何限制。
实施例1:3-TYP对EAE小鼠行为学的改善作用
1.1实验性自身免疫性脑脊髓炎小鼠模型的建立及给药情况
实验原理
C57BL/6小鼠用MOG28-55诱导EAE模型。
实验方法
雌性C57BL/6小鼠,6-8周龄,体重18-20g,适应性喂养3-5天后,对其皮下注射MOG28-55300μg并腹腔注射百日咳毒素600ng,建立实验性自身免疫性脑脊髓炎动物模型(EAE)。同时设置正常对照组。建模14天后动物开始发病,出现不同程度的肢体瘫痪。选择出现肢体瘫痪的小鼠为实验性自身免疫性脑脊髓炎模型。
免疫后将雌性C57BL/6小鼠随机分为3组,EAE对照组、30mg/kg 3-TYP给药组和30mg/kg Honokiol给药组(Sirt3激动剂)。分组后,每日一次腹腔注射。正常对照组和EAE模型组给予同体积溶剂对照(2%DMSO+40%PEG300+5%Tween-80+53%生理盐水)。自免疫之日起,3-TYP和Honokiol连续给药至建模第28天。每天测疾病评分,记录动物死亡情况。于免疫后第7天、15天、22天和27天测定动物的悬挂分级,27天测定动物在铁丝网上的悬挂时间。
实验结果
免疫后第14天动物开始发病,出现体重减轻、神经功能评分降低。
1.2 3-TYP对EAE小鼠疾病评分的影响
实验方法
实验小鼠在建模后每天进行疾病评分,评分标准如下:0分:正常小鼠;0.5分:尾部无力;1分:尾部完全瘫痪;1.5分:一后肢无力;2分:两后肢均无力;2.5分:一后肢瘫痪,另一后肢无力;3分:两后肢均瘫痪;3.5分:部分前肢无力;4分:部分前肢瘫痪;4.5分:前肢完全瘫痪;5分:死亡。
实验结果
本实验中,发病后EAE模型组小鼠疾病评分显著高于正常对照组,给药后,3-TYP给药组小鼠整体发病症状减轻,且疾病评分显著低于EAE模型组,而Sirt3激动剂Honokiol给药组小鼠疾病评分无明显改善,证实了3-TYP作为Sirt3抑制剂治疗对EAE小鼠的神经功能具有显著改善作用。结果见图1。
1.3 3-TYP对EAE小鼠悬挂时间的影响
实验方法
建模后第27天,测定小鼠从180°铁丝网上的掉落时间,时间>300s按300s算。
实验结果
本实验中,与正常对照组相比,EAE模型组小鼠的在铁丝网上的悬挂时间显著降低,3-TYP可以延长EAE小鼠的悬挂时间,而Sirt3激动剂Honokiol给药组EAE小鼠小鼠在铁丝网上的悬挂时间无明显改善,证实了Sirt3抑制剂3-TYP治疗对EAE小鼠的运动功能具有显著改善作用。结果见图2及表1。
表1 3-TYP对MOG诱导的EAE小鼠悬挂时间的影响
Mean±SEM(n=6~9).
###P<0.001vs.正常对照组,**P<0.01vs.EAE模型组.
1.4 3-TYP对EAE小鼠悬挂分级的影响
实验方法
建模后第7、15、22和27天,将小鼠前爪悬挂于距地面30cm的平衡绳上,观察小鼠在平衡绳上的肢体悬挂状态并进行评分,分级标准如下:5分:抓住绳子并能用后肢拉,尾巴紧绕绳子;4分:抓住绳子并能用后肢拉,尾巴抬起但不能绕绳;3分:抓住绳子并能用后肢拉,尾巴下垂;2分:抬起后肢,抓住绳子但不能拉;1分:抬起后肢,但不能抓住绳子;0分:不能抬起后肢。
实验结果
在本实验中,与正常对照组相比,EAE模型组小鼠发病之后悬挂评分显著降低,给药之后,与EAE模型组相比,3-TYP给药组的EAE小鼠悬挂评分显著增加,且呈时间依赖性,Sirt3激动剂Honokiol给药组EAE小鼠的悬挂评分无明显改善。结果见图3及表2。
表2 3-TYP对MOG诱导的EAE小鼠悬挂分级的影响
Mean±SEM(n=6~9).
##P<0.01###P<0.001vs.正常对照组;**P<0.01vs.EAE模型组。
实施例2:3-TYP对EAE模型小鼠脊髓炎性细胞浸润及脱髓鞘的影响
2.1EAE小鼠模型的建立及给药情况
实验原理、实验方法、实验结果同实施例1.1。
2.2 3-TYP对EAE小鼠脊髓内炎性细胞浸润情况的影响
实验方法
建模后第28天,每组取3只小鼠用4%三溴乙醇进行麻醉。先用生理盐水进行灌流,待肝脏颜色发白,再用4%多聚甲醛灌流至动物肢体发硬。断头,取脊髓腰膨大部分置于4%多聚甲醛中固定。脊髓腰膨大部分制作石蜡切片,进行苏木素-伊红(H&E)染色,观察脊髓炎性细胞浸润情况。
实验结果
本实验中,与正常对照组相比,EAE模型组小鼠脊髓炎症细胞浸润显著,30mg/kg3-TYP可以显著抑制EAE小鼠脊髓炎性细胞的浸润,而Sirt3激动剂Honokiol给药组EAE小鼠脊髓炎症细胞浸润无明显改善,证实了3-TYP作为Sirt3抑制剂可改善EAE小鼠脊髓内炎性细胞浸润。结果见图4。
2.3 3-TYP对EAE小鼠脊髓内髓鞘脱失情况的影响
实验方法
建模后第28天,每组取3只小鼠用4%三溴乙醇进行麻醉。先用生理盐水进行灌流,待肝脏颜色发白,再用4%多聚甲醛灌流至动物肢体发硬。断头,取脊髓腰膨大部分置于4%多聚甲醛中固定。脊髓腰膨大部分制作石蜡切片,进行固蓝染色(LFB)染色,观察脊髓内髓鞘脱失情况。
实验结果
本实验中,LFB染色后,与正常对照组相比,EAE模型组小鼠脊髓呈现脱髓鞘病灶,面积较大。Sirt3抑制剂3-TYP可以使EAE小鼠脊髓白质区域泛白面积减小,有效地改善脱髓鞘情况,而Sirt3激动剂Honokiol给药组EAE小鼠脊髓白质髓鞘脱失情况无明显改善。结果见图5。
实施例3:3-TYP对EAE小鼠脊髓促炎因子的影响及对M1/M2型小胶质细胞极化状态的调节
3.1EAE小鼠模型的建立及给药情况
实验原理、实验方法、实验结果同实施例1.1。
3.2 3-TYP对EAE小鼠脊髓促炎因子mRNA水平的影响
实验方法
建模后第28天,每组取4只小鼠用4%三溴乙醇进行麻醉。脱颈处死后断头,取脊髓并提取RNA,逆转录为cDNA,采用qRT-PCR技术检测促炎因子TNF-α、IL-6、IL-1β和MCP-1的mRNA水平。
实验结果
本实验中,与正常对照组相比,EAE模型组小鼠脊髓促炎因子TNF-α、IL-6、IL-1β和MCP-1的mRNA水平显著升高,而3-TYP可显著抑制EAE小鼠脊髓促炎因子TNF-α、IL-6、IL-1β和MCP-1的mRNA水平。结果见图6。
3.3 3-TYP对EAE小鼠脊髓M1/M2型小胶质细胞极化状态的调节
实验方法
建模后第28天,每组取4只小鼠用4%三溴乙醇进行麻醉。脱颈处死后断头,取脊髓并提取RNA,逆转录为cDNA,采用qRT-PCR技术检测M1型小胶质细胞标志物CD16、CD32和CD86以及M2型小胶质细胞标志物CD206的mRNA水平。
实验结果
本实验中,3-TYP可抑制EAE小鼠脊髓M1型小胶质细胞标志物CD16、CD32和CD86mRNA水平的表达,从而抑制EAE小鼠脊髓M1型小胶质细胞极化;且3-TYP可提高M2型小胶质细胞标志物CD206 mRNA水平的表达,促进小胶质细胞向M2型转化。结果见图7。
Claims (8)
1.如式(I)所示的3-TYP在制备预防、缓解和/或治疗自身免疫性脱髓鞘疾病药物中的应用;
2.根据权利要求1的应用,其特征在于,所述自身免疫性脱髓鞘疾病包括中枢神经系统的脱髓鞘自身免疫病、影响外周神经系统的脱髓鞘自身免疫病,慢性炎性脱髓鞘性多发性神经病,抗-MAG周围神经病,运动与感觉神经病,遗传学感觉运动神经病,腓骨肌萎缩症,进行性神经性腓骨肌萎缩症;所述的中枢神经系统的脱髓鞘自身免疫病包括多发性硬化症,视神经脊髓炎谱系疾病,急性播散性脑脊髓炎,白质脑炎和横贯性脊髓炎。
3.根据权利要求2的应用,其特征在于,所述的影响外周神经系统的脱髓鞘自身免疫病包括急性炎性脱髓鞘多发性神经病。
4.根据权利要求2的应用,其特征在于,所述多发性硬化症包括复发缓解型多发性硬化症、原发进展型多发性硬化症、继发进展型多发性硬化症和进展复发型多发性硬化症。
5.一种药物组合物在预防、缓解和/或治疗自身免疫性脱髓鞘疾病药物中的应用,其特征在于,所述的药物组合物含有有效剂量的如式(I)所示的3-TYP,以及任选的药学可接受的药用赋形剂,
6.根据权利要求5的应用,其特征在于,所述的药物组合物除含有3-TYP作为药物活性成分外,还含有其他活性成分。
7.根据权利要求5-6任一项的应用,其特征在于,所述的药物组合物包括如下的剂型:溶液、混悬液、冻干粉针、乳剂、丸剂、胶囊、粉末、控制释放、持续释放制剂及微粒体给药系统的形式。
8.根据权利要求5的应用,其特征在于,所述的药用赋形剂包括淀粉、糊精、多甲基纤维素钠、硬脂酸镁、滑石粉。
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