CN117137916A - 盐酸去亚甲基小檗碱在制备预防或治疗银屑病药物的应用 - Google Patents
盐酸去亚甲基小檗碱在制备预防或治疗银屑病药物的应用 Download PDFInfo
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- CN117137916A CN117137916A CN202311224532.9A CN202311224532A CN117137916A CN 117137916 A CN117137916 A CN 117137916A CN 202311224532 A CN202311224532 A CN 202311224532A CN 117137916 A CN117137916 A CN 117137916A
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- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
Abstract
本发明涉及生物医药领域,具体涉及盐酸去亚甲基小檗碱在制备预防或治疗银屑病药物的应用。本发明通过体外实验发现盐酸去亚甲基小檗碱能够抑制永生化角质形成细胞的增殖与分化;通过体外实验发现能够缓解咪喹莫特诱导的小鼠银屑病样症状。结果说明盐酸去亚甲基小檗碱(DMB)能够抑制角质形成细胞过度增殖以及在抗炎方面治疗咪喹莫特诱导的银屑病,扩大了盐酸去亚甲基小檗碱应用范围。
Description
技术领域:
本发明涉及生物医药领域,具体涉及盐酸去亚甲基小檗碱在制备预防或治疗银屑病药物的应用。
技术背景:
银屑病(psoriasis)是一种炎症性自身免疫性皮肤病。影响着全世界超过6000万的成人和儿童。银屑病的特征表现为皮肤病变增加、鳞片状红斑、表皮增生、角化细胞异常分化。炎症细胞浸润多见于头皮、肘部和膝关节。
银屑病的发病机制复杂,尚不完全清楚。是由多种免疫细胞与角质形成细胞以及其他皮肤细胞相互作用的结果。主要表现为大量免疫细胞浸润,角质形成细胞过度增殖的自身免疫引起的慢性炎症疾病。银屑病的早期角质形成细胞产生触发因子,Th17、Th22和产生1型干扰素(IFN)-γ的T细胞扩张。银屑病晚期T细胞浸润出现,在细胞因子的影响下,角质形成细胞增生并表现出改变的分化程序。在疾病的扩增/记录阶段,角质形成细胞和免疫细胞之间不断的相互作用进一步放大了炎症和增生。
目前还没有特效药,还不能够完全治愈银屑病。传统的系统性药物,主要用于重度症状,反应较大,又有不小的副作用。例如甲氨蝶呤会引起呕吐、畸形、肺部毒性;环孢素A会导致患者肾小球硬化等。生物制剂相比于传统药物疗效更佳显著,且耐受性好。生物制剂主要靶向银屑病的重要靶点,例如靶向TNF-α的阿达利单抗、靶向IL-17的苏金单抗、靶向IL-23的古塞库单抗等。尽管许多生物制剂非常有效,但其价格十分昂贵,而且并非所有患者的反应方式都相同。有些人可能根本没有反应(初次治疗失败),或者最初的反应随后在几个月到几年的时间里消失(继发性失败)。停用时间在不同的生物制品之间是不同的,治疗失败的风险随着患者以前接受过的生物制品的数量而增加。因此对于开发一种安全、高效且经济的新型的治疗银屑病药物十分有必要。
从目前研究来看,抑制角质形成细胞增殖作用、抑制角质形成细胞分化,降低炎症反应、减少对于免疫细胞趋化作用等为目前寻找治疗银屑病药物的有效评价途径。鉴于目前银屑病目前还不能有效被治愈,给患者身心带来巨大痛苦,寻找改善、治疗银屑病药物迫在眉睫。盐酸去亚甲基小檗碱,如式(Ⅰ)所示。
盐酸去亚甲基小檗碱(式Ⅰ)的英文名为Demethyleneberberine Hydrochloride或Demethyleneberberine Chloride。本发明专利将它简称为DMB。式(Ⅰ)中的骨架结构为去亚甲基小檗碱,它是盐酸去亚甲基小檗碱的活性成份。国际纯粹与应用化学联合会(IUPAC)将式(Ⅰ)中的有机结构部分去亚甲基小檗碱命名9,10-dimethoxy-5,6-dihydroisoquinolino[2,1-b]isoquinolin-7-ium-2,3-diol,其中文名为9,10-二甲氧基-5,6-二氢异喹啉[2,1-b]异喹啉-7-鎓-2,3-二羟基。它的分子式:C19H18NO4+,分子量为:324.35。化学文摘号(CAS)为:25459-91-0。去亚甲基小檗碱可以与无机酸或有机酸形成多种盐,如氯化盐、硫酸盐、磷酸盐、溴化盐、碘化盐、枸橼酸盐、延胡索酸盐、马来酸盐、苹果酸盐和琥珀酸盐等分子形式存在。
迄今为止,现有技术中没有关于盐酸去亚甲基小檗碱对银屑病治疗作用的记载和报道。发明内容:
发明目的
为了克服现有技术的不足,本发明的目的在于提供盐酸去亚甲基小檗碱(DMB)作为防治银屑病的新用途。
技术方案
盐酸去亚甲基小檗碱在制备预防或治疗银屑病药物中的应用,其中盐酸去亚甲基小檗碱结构式如(Ⅰ)所示。
一种药物组合物,其特征在于:含有药物有效剂量的盐酸去亚甲基小檗碱及药学上可接受的辅料。
所述的应用,其特征在于:去亚甲基小檗碱不局限于盐酸盐形式,还包括磷酸盐、硫酸盐以及其它去亚甲基小檗碱成盐形式。
本发明所用盐酸去亚甲基小檗碱产品采用常规化学与分离纯化制得。本实验室采用高效液相色谱(HPLC)分析检测,其纯度达99%以上,并经过化学法、质谱法和核磁共振法分析鉴定,表明本实验室所用的盐酸去亚甲基小檗碱产品化学结构正确。此项研究表明盐酸去亚甲基小檗碱其纯度和化学结构符合开展体内、体外生物学活性和药理作用研究要求。
本发明还涉及及含有作为活性成分的盐酸去亚甲基小檗碱和常规药物赋形剂或辅剂的药物组合物。通常本发明药物组合物含有0.1~95%重量的盐酸去亚甲基小檗碱。在单元剂型中本发明化合物一般含量为0.1~100mg。
本发明化合物的药物组合物可根据本领域公知的方法制备。用于此目的时,如果需要,可将本发明化合物与一种或多种固体或液体药物赋形剂和/或辅剂结合,制成可作为人药或兽药使用的适当的施用形式或剂量形式。
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、肌肉、皮下、鼻腔、口腔黏膜、皮肤、腹膜或直肠等。
本发明化合物或含有它的药物组合物的给药途径可为注射给药。注射包括静脉注射、肌肉注射、皮下注射、皮内注射和穴位注射等。
给药剂型可以是液体剂型、固体剂型。如液体剂型可以是真溶液类、胶体类、微粒剂型、乳剂剂型、混悬剂型。其他剂型例如片剂、胶囊、滴丸、气雾剂、丸剂、粉剂、溶液剂、混悬剂、乳剂、颗粒剂、栓剂、冻干粉针剂等。
本发明化合物可以制成普通制剂、也可以是缓释制剂、控释制剂、靶向制剂及各种微粒给药系统。
例如为了将单位给药剂型制成片剂,可以广泛使用本领域公知的各种载体。关于载体的例子是,例如稀释剂与吸收剂,如淀粉、糊精、硫酸钙、乳糖、甘露醇、蔗糖、氯化钠、葡萄糖、尿素、碳酸钙、白陶土、微晶纤维素、硅酸铝等;湿润剂与粘合剂,如水、甘油、聚乙二醇、乙醇、丙醇、淀粉浆、糊精、糖浆、蜂蜜、葡萄糖溶液、阿拉伯胶浆、明胶浆、羧甲基纤维素钠、紫胶、甲基纤维素、磷酸钾、聚乙烯吡咯烷酮等;崩解剂,例如干燥淀粉、海藻酸盐、琼脂粉、褐藻淀粉、碳酸氢钠与枸橼酸、碳酸钙、聚氧乙烯山梨醇脂肪酸酯、十二烷基磺酸钠、甲基纤维素、乙基纤维素等;崩解抑制剂,例如蔗糖、三硬脂酸甘油酯、可可脂、氢化油等;吸收促进剂,例如季铵盐、十二烷基硫酸钠等;润滑剂,例如滑石粉、二氧化硅、玉米淀粉、硬脂酸盐、硼酸、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。
例如为了将给药单元制成胶囊,将有效成份本发明化合物盐酸去亚甲基小檗碱与上述的各种载体混合,并将由此得到的混合物置于硬的明胶胶囊或软胶囊中。也可将有效成分本发明化合物制成微囊剂,混悬于水性介质中形成混悬剂,亦可装入硬胶囊中或制成注射剂应用。
例如,将本发明化合物盐酸去亚甲基小檗碱制成注射用制剂,如溶液剂、混悬剂溶液剂、乳剂、冻干粉针剂,这种制剂可以是含水或非水的,可含一种和/或多种药效学上可接受的载体、稀释剂、粘合剂、润滑剂、防腐剂、表面活性剂、分散剂、渗透压调节剂、增溶剂和pH调节剂。如稀释可选用水、乙醇、聚乙二醇、1,3-丙二醇、乙氧基化的异硬脂醇、多氧化的异硬脂醇、聚氧乙烯山梨醇脂、脂肪酸酯等。渗透压调节剂可以是氯化钠、甘露醇、甘油、葡萄糖、磷酸盐、醋酸盐等;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调节剂可以是磷酸盐、醋酸盐、盐酸、氢氧化钠等。如制备冻干粉针剂,还可以加入甘露醇、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、甜味剂或香料等。这些辅料是本领域常用的。
本发明所用的无菌介质都可以通过本领域技术人员众所周知的标准技术制得。可将它们灭菌,例如通过经由细菌过虑器过滤、通过向组合物中加入灭菌剂、通过将组合物放射处理、或通过将组合物加热灭菌。还可以在临用前将它们制成无菌可注射介质。
为了达到用药目的,增加治疗效果,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。当然用于实施本发明化合物的给药途径取决于疾病和需要治疗的部位。因为本发明化合物的药动学和药效学特征会有某种程度的不同,因此在组织中获得治疗浓度的最优选方法是逐渐增加剂量并监测临床效果。对于这样的逐渐增加治疗剂量,初始剂量将取决于给药途径。
对于任何特定患者,本发明化合物药物组合物的给药剂量取决于许多因素,例如所要预防或治疗疾病的性质和严重程度,患者或动物的性别、年龄、性格及个体反应,给药途径、给药次数、治疗目的,因此本发明的治疗剂量可以有较大范围的变化。根据所治疗患者的病症,可能必须对剂量作出某些改变,并且在任何情况下,都由医师决定个体患者的合适剂量。
给药剂量是指不包括载体重量(当使用载体时)在内的化合物的重量。一般来讲,本发明中药学成分的使用剂量是本领域技术人员公知的。可以根据本发明化合物组合物中最后的制剂中所含有的实际药物剂量,加以适当的调整,以达到其治疗有效量的要求,完成本发明的预防或治疗目的。可以是单一剂量形式给药或分成几个,例如二、三或四个剂量形式给药;这受限于给药医生的临床经验以及包括运用其它治疗手段的给药方案。本发明的化合物或组合物可单独服用,或与其他治疗药物或对症药物合并使用并调整剂量。
有益效果
银屑病是本领域难治的疾病,缺乏有效的治疗手段。而本发明通过直接给药角质形成细胞(Hacat),同时建立咪喹莫特诱导的银屑病模型,观察盐酸去亚甲基小檗碱(DMB)对银屑病是否具有预防或治疗效果。研究结果表明,首次发现盐酸去亚甲基小檗碱(DMB)对银屑病有防治作用,为开发和研究治疗银屑病药物提供新的思路。
具体而言:
在体外实验中,角质形成细胞过度增殖是银屑病发生的直接表现,故可以通过考察药物对于人源永生化角质形成细胞(Hacat细胞)的抑制作用反应治疗作用,具体通过细胞培养、MTT法、集落形成实验分析了盐酸去亚甲基小檗碱(DMB)对于人源永生化角质形成细胞(Hacat细胞)的增殖抑制作用。结果表明:DMB对正常肝细胞(L02细胞)无毒性,对于Hacat细胞的增殖有显著抑制作用。本发明发现对于角质形成细胞增殖分化关键基因的表达也有显著抑制。综上表明DMB对于角质形成细胞的增殖分化有显著抑制作用。银屑病作为一种慢性炎症疾病,控制炎症能够有效缓解银屑病。本发明发现DMB能够有效抑制Hacat细胞炎症反应。角质形成细胞对于免疫细胞的趋化作用在银屑病的发生也至关重要的,本发明发现DMB能够有效抑制Hacat细胞表达趋化因子。
在体内实验中,本发明以BALB/c小鼠为动物实验模型,考察DMB对于咪喹莫特诱导(imiquimod,IMQ)的银屑病的防治作用。具体而言,提前一周开始腹腔注射DMB溶液,给药组分别设置20mg/kg(IP)和40mg/kg(IP)高低两个剂量。第6天开始对小鼠背部约2×3cm2区域脱毛,第8天开始涂抹咪喹莫特进行造模,同时继续给药,共造模六天,每天观察小鼠背部皮肤的变化,拍照,并且对其严重程度进行打分。第14天解剖小鼠。实验结果表明DMB能够显著改善银屑病引起的炎症反应,皮肤变厚,红斑增多以及鳞屑产生。小鼠背部皮肤病理学检测显示,DMB能够显著改善皮肤角质层的增厚以及皮肤炎性细胞的浸润。同时发现DMB对于小鼠脾指数改善效果显著。以上结果表明DMB对于银屑病的防治有显著作用。
附图说明
图1DMB作用L02细胞24h对其细胞活力的影响;
图2DMB给药Hacat细胞24h对其抑制作用的结果;
图3DMB给药Hacat细胞的集落形成实验的结果,A为集落形成实验结果,B为统计结果;
图4DMB给药Hacat细胞24h对其增殖分化关键基因表达的影响;A为KRT5,B为KRT6,C为KRT17,D为involucrin;
图5DMB给药Hacat细胞24h对其产生趋化因子的影响,A为CCL2,B为CCL5;
图6DMB给药对LPS诱导的Hacat细胞产生炎症因子的影响,A为IL-1β,B为IL-6,C为TNFα;
图7DMB给药Hacat细胞24h对其周期蛋白以及周期蛋白激酶的免疫印迹结果(A)及CDK4的灰度分析图(B),Cyclin E的灰度分析图(C);
图8DMB对IMQ诱导银屑病小鼠背部皮肤外观的影响;
图9DMB防治IMQ诱导银屑病小鼠统计结果;A为红斑评分,B为皮肤厚度评分,C为鳞屑评分,D为PASI总评分;
图10DMB对IMQ诱导银屑病小鼠脾指数的影响,A解剖照片,B为统计结果;
图11DMB防治IMQ诱导的银屑病小鼠HE染色图(×100)。
具体实施方式
下面的实施例可以帮助本领域的技术人员更全面的理解本发明,但不以任何方式限制本发明。
术语
DMB:盐酸去亚甲基小檗碱
IMQ:咪喹莫特
KRT:角蛋白
Involucrin:内皮蛋白
IL-1β:白细胞介素-1β
IL-6:白细胞介素-1β
TNF-α:肿瘤坏死因子
CCL2:趋化因子配体2
CCL5:趋化因子配体5
CDK4:依赖细胞周期素激酶4
Cyclin E:细胞周期蛋白E
IP:腹腔注射
实施例1盐酸去亚甲基小檗碱(DMB)对人肝细胞L02细胞没有毒性
方法:以L02细胞为研究对象,将L02细胞铺入96孔板中,待细胞贴壁后,分别加入10、20、40、80μM的盐酸去亚甲基小檗碱,培养24h后,采用MTT法检测试剂盒,检测细胞增殖。
结果:盐酸去亚甲基小檗碱对人肝细胞L02细胞没有不产生毒性,体现了药物的安全性。结果如图1所示。
实施例2盐酸去亚甲基小檗碱(DMB)能抑制人永生化角质形成细胞(Hacat)细胞的增殖
方法:以Hacat细胞为研究对象,将Hacat细胞铺入96孔板中,待细胞贴壁后,分别加入10、20、40、80μM的盐酸去亚甲基小檗碱,培养24h后,采用MTT法检测试剂盒,检测细胞增殖。以Hacat细胞为研究对象,将Hacat细胞铺入6孔板中,待细胞贴壁后,分别加入10、20、40、80μM的盐酸去亚甲基小檗碱,培养2weeks后,4%多聚甲醛固定,结晶紫染色,最后对细胞集落计数。
结果:角质形成细胞过度增殖是银屑病的直接表现。盐酸去亚甲基小檗碱对于Hacat细胞的细胞活力明显抑制作用。结果如图2所示。集落形成实验显示盐酸去亚甲基小檗碱能够显著抑制Hacat细胞的增殖。结果如图3所示。
实施例3盐酸去亚甲基小檗碱(DMB)抑制Hacat细胞增殖分化关键基因的表达
方法:以Hacat细胞为研究对象,采用RT-PCR法,从细胞水平检测DMB对于Hacat细胞增殖分化关键基因的影响。将Hacat细胞接种于培养板中待其贴壁后取出,给予含有DMB(10、20uM)的细胞培养液处理24h后取出,用qRT-PCR法检测角蛋白(KRT)5、6、17以及Involucrin的表达。
结果:qRT-PCR法显示,DMB可降低Hacat细胞增殖分化的关键基因的表达,从分子水平表明DMB能够抑制角质形成细胞的过度增殖。结果如图4所示。
实施例4盐酸去亚甲基小檗碱(DMB)抑制Hacat细胞对T细胞、巨噬细胞的趋化作用。
方法:以Hacat细胞为研究对象,采用RT-PCR法,从细胞水平检测DMB降低Hacat细胞增殖分化关键基因的表达。将人永生化角质形成细胞细胞(Hacat)接种于培养板中待其贴壁后取出,给予含有DMB(10、20uM)的细胞培养液处理24h后取出,用qRT-PCR法检测趋化因子CCL2、5的表达。
结果:银屑病的特征表现为各种免疫细胞,特别是T细胞、巨噬细胞在病损处的聚集,从而造成炎性放大。qRT-PCR法显示,DMB可降低Hacat细胞趋化因子CCL2、5的基因表达,减弱对于巨噬细胞以及T细胞的趋化作用。结果如图5所示。
实施例5盐酸去亚甲基小檗碱(DMB)减轻LPS诱导的Hacat细胞的炎症反应
方法:以Hacat细胞为研究对象,脂多糖(LPS)为诱导试剂,采用RT-PCR法,从细胞水平检测DMB减轻脂多糖LPS(10ug/ml)诱导的炎症反应。将Hacat细胞接种于培养板中待其贴壁后取出,给予含有DMB(10uM、20uM)+LPS(10ug/ml)或LPS(10ug/ml)的细胞培养液处理24h后取出,用qRT-PCR法检测TNF-α、IL-1β和IL-6炎症因子。
结果:qRT-PCR法显示,DMB可缓解LPS诱导的Hacat细胞炎症反应。结果如图6所示。
实施例6盐酸去亚甲基小檗碱(DMB)抑制Hacat细胞细胞周期相关蛋白的表达
方法:将Hacat细胞接种于6孔培养板中待其贴壁后取出,给予含有DMB(10uM、20uM)的细胞培养液处理24h后取出,用Western blot法检测CDK4和Cyclin E的表达。
结果:Western blot法显示,DMB可显著降低CDK4以及Cyclin E的表达,阻滞Hacat细胞细胞周期的进行,从而阻滞角质形成细胞的过度增殖。结果如图7所示。
实施例7DMB能改善IMQ诱导银屑病小鼠背部皮肤损伤
方法:成年BALB/c雄性小鼠,6-8周龄,体重20-22g,随机分为4组,每组5只。4组分别为正常对照组,模型组,DMB低剂量组(20mg/kg)、DMB高剂量组(40mg/kg)。给药组连续预先给药7天,每天一次,其余各组给予同体积赋形剂。第6天,对每组小鼠背部进行剃毛处理,剃出约2×3cm2大小区域。第8天开始给除正常对照组外其他组涂抹62.5mg的5%咪喹莫特(IMQ)乳膏。继续每天给药,观察小鼠背部皮肤变化,并对其背部进行拍照,同时对严重程度打分。皮肤厚度以及红斑等级分别为无、轻微、中等、严重、非常严重,对应分数为0-4。鳞屑等级分别为无、开始出现、部分区域出现、大部分区域出现、全部区域覆盖,对应分数为0-4(评分打分标准根据参考文献“Yue L,AilinW,Jinwei Z,et al.PSORI-CM02 amelioratespsoriasis in vivo and in vitro by inducing autophagy via inhibition of thePI3K/Akt/mTOR pathway[J].Phytomedicine:international journal ofphytotherapyandphytopharmacology,2019,64:153054”并根据实际实验情况来给出的)。第14天对小鼠称重,处死,摘取背部皮肤以及脾脏。脾脏在生理盐水清洗干净,进行称重。取不同小鼠皮肤部分以4%多聚甲醛固定24小时,进行HE染色进行病理学检查。
结果:DMB能显著改善IMQ诱导银屑病小鼠背部皮肤的炎症、角质形成细胞过度增殖引起的鳞屑产生,改善皮肤变厚。结果如图8,9所示。
实施例8DMB能改善IMQ诱导银屑病小鼠炎性反应
方法:成年BALB/c雄性小鼠,6-8周龄,体重20-22g,随机分为4组,每组5只。4组分别为正常对照组,模型组,DMB低剂量组(20mg/kg)、DMB高剂量组(40mg/kg)。给药组连续预先给药7天,每天一次,其余各组给予同体积赋形剂。第6天,对每组小鼠背部进行剃毛处理,剃出约2×3cm2大小区域。第8天开始给除正常对照组外其他组涂抹62.5mg的5%咪喹莫特(IMQ)乳膏。继续每天给药,观察小鼠背部皮肤变化,并对其背部进行拍照,同时对严重程度打分。皮肤厚度以及红斑等级分别为无、轻微、中等、严重、非常严重,对应分数为0-4。鳞屑等级分别为无、开始出现、部分区域出现、大部分区域出现、全部区域覆盖,对应分数为0-4。第14天对小鼠称重,处死,摘取背部皮肤以及脾脏。脾脏在生理盐水清洗干净,进行称重。取不同小鼠皮肤部分以4%多聚甲醛固定24小时,进行HE染色进行病理学检查。
结果:DMB能改善IMQ诱导银屑病小鼠脾脏脾指数,缓解炎症反应。结果如图10所示。
实施例9DMB能改善IMQ诱导银屑病小鼠背部皮肤病理学特征
方法:成年BALB/c雄性小鼠,6-8周龄,体重20-22g,随机分为4组,每组5只。4组分别为正常对照组,模型组,DMB低剂量组(20mg/kg)、DMB高剂量组(40mg/kg)。给药组连续预先给药7天,每天一次,其余各组给予同体积赋形剂。第6天,对每组小鼠背部进行剃毛处理,剃出约2×3cm2大小区域。第8天开始给除正常对照组外其他组涂抹62.5mg的5%咪喹莫特(IMQ)乳膏。继续每天给药,观察小鼠背部皮肤变化,并对其背部进行拍照,同时对严重程度打分。皮肤厚度以及红斑等级分别为无、轻微、中等、严重、非常严重,对应分数为0-4。鳞屑等级分别为无、开始出现、部分区域出现、大部分区域出现、全部区域覆盖,对应分数为0-4。第14天对小鼠称重,处死,摘取背部皮肤以及脾脏。脾脏在生理盐水清洗干净,进行称重。取不同小鼠皮肤部分以4%多聚甲醛固定24小时,进行HE染色进行病理学检查。
结果:通过比较HE染色结果,发现DMB能够改善角质层的增厚,缓解免疫细胞的浸润,改善银屑病小鼠皮肤病理学表征。结果如图11所示。
Claims (3)
1.盐酸去亚甲基小檗碱在制备预防或治疗银屑病药物中的应用,其中盐酸去亚甲基小檗碱结构式如(Ⅰ)所示。
2.一种药物组合物,其特征在于:含有药物有效剂量的盐酸去亚甲基小檗碱及药学上可接受的辅料。
3.根据权利要求1所述的应用,其特征在于:去亚甲基小檗碱不局限于盐酸盐形式,还包括磷酸盐、硫酸盐以及其它去亚甲基小檗碱成盐形式。
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