CN114028372B - 谷氨酰胺作为活性成分在制备银屑病治疗药物中的应用、银屑病治疗药物及其制备方法 - Google Patents
谷氨酰胺作为活性成分在制备银屑病治疗药物中的应用、银屑病治疗药物及其制备方法 Download PDFInfo
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Abstract
本发明涉及一种谷氨酰胺作为活性成分在制备银屑病治疗药物中的应用、银屑病治疗药物及其制备方法。本发明的研究人员通过长期研究,根据银屑病皮损面积和严重程度指数(PASI)评分及皮损HE染色,首先发现并证明谷氨酰胺对银屑病有显著的治疗作用,能有效减轻MDSCs细胞群、Th1、Th17细胞群的增多以及Tregs细胞群的减少。本发明给谷氨酰胺提供了新用途,为治疗银屑病提供了一种新的药物。研究表明,谷氨酰胺无论是应用于外用药物还是内用药物,对于治疗银屑病均有明显的药效,应用前景广泛,具有较大的推广应用价值。而且,由于谷氨酰胺是人体内含量最丰富的氨基酸,其对人体的副作用小,也降低了研发成本和制造成本。
Description
技术领域
本发明涉及银屑病治疗技术领域,特别是涉及一种谷氨酰胺作为活性成分在制备银屑病治疗药物中的应用、银屑病治疗药物及其制备方法。
背景技术
银屑病是一种常见的慢性、复发性、炎症性皮肤病,临床上主要表现为红斑、鳞屑,其组织病理有特异性,表现为表皮角质细胞过度增殖,角化过度伴角化不全,棘层肥厚,真皮浅层血管周围稀疏炎症细胞浸润等。银屑病在自然人群中的发病率为0.1%~3%,其发病机制复杂,易反复发作。
大多数银屑病是轻中型患者,外用药物治疗是主要的治疗方法,占有不可或缺的地位。寻常型银屑病患者80%为轻度,因此局部治疗是寻常型银屑病首选的治疗方案。目前常用的银屑病外用药物有糖皮质激素、维A酸、维生素D衍生物、地蒽酚、焦油制剂以及钙调磷酸酶抑制剂等。地蒽酚、焦油制剂和糖皮质激素因副作用较大使用受限,而维A酸、钙调磷酸酶抑制剂和维生素D衍生物的治疗效果不是十分理想。最近上市的糖皮质激素与维生素D衍生物的复方制剂卡泊三醇倍他米松软膏的效果较卡泊三醇稍优,但其成本高昂。可选择的外用药物很有限、容易出现耐受性一直以来是银屑病局部治疗的瓶颈。
此外,在***给药中,甲氨蝶呤、环孢素、维A酸类、硫唑嘌呤、来氟米特、吗替麦考酚酯、糖皮质激素、抗生素和生物制剂是治疗重症银屑病患者的常用药物。虽然这些药物对患者的病情有治愈作用,但是其对患者其他***,如肝肾的影响是日常诊疗中特别需要重视的。同时,如甲氨蝶呤、硫唑嘌呤和吗替麦考酚酯的骨髓抑制效应、环孢素的神经***不良反应、糖皮质激素长期使用带来的激素过量都影响着这些药物的使用范围。生物制剂虽然疗效快,但是价格昂贵,使用条件局限也限制其在银屑病治疗中的价值。
因此,寻找一种疗效好、副作用小的新药对于银屑病的治疗具有重要意义。
发明内容
基于此,有必要提供一种疗效较好、副作用小的治疗银屑病的新药物。
本发明的一个方面,提供了谷氨酰胺作为活性成分在制备银屑病治疗药物中的应用。
本发明的另一方面还提供了一种银屑病治疗药物,其活性成分主要由谷氨酰胺组成。
在其中一个实施例中,所述银屑病治疗药物的剂型为溶液剂、洗剂、搽剂、软膏剂、硬膏剂、糊剂或贴剂。
在其中一个实施例中,所述银屑病治疗药物的剂型为溶液剂,主要由谷氨酰胺和溶剂组成。
在其中一个实施例中,所述溶剂为生理盐水。
在其中一个实施例中,所述银屑病治疗药物中,所述谷氨酰胺的浓度为0.02g/mL~2g/mL。
在其中一个实施例中,所述银屑病治疗药物中,所述谷氨酰胺的浓度为0.04g/mL。
在其中一个实施例中,所述银屑病治疗药物还包括稀释剂、防腐剂、缓冲剂、崩解剂、抗氧剂、助悬剂、着色剂和赋形剂中的一种或多种。
在其中一个实施例中,所述稀释剂选自丙二醇、植物油和矿物油中的一种或多种,所述防腐剂选自山梨酸、山梨酸甲酯、对羟基苯甲酸甲酯、对羟基苯甲酸乙酯、对羟基苯甲酸丙酯、对羟基苯甲酸丁酯、对羟基苯甲酸苄酯、对羟基苯甲酸甲酯钠、苯甲酸和苯甲醇中的一种或多种,所述缓冲剂选自磷酸氢钠、磷酸二氢钠、枸橼酸钠、酒石酸钠和醋酸钠中的一种或多种。
本发明的另一方面还提供了一种银屑病治疗药物的制备方法,其包括以下步骤:将谷氨酰胺与溶剂混合,得到所述银屑病治疗药物。
谷氨酰胺(Glutamine,2-氨基-5-羧基戊酰胺)是人体内含量最丰富的氨基酸,在细胞***中起着至关重要的作用。除此之外,人们发现其代谢过程不仅为细胞代谢中提供碳,提供的氮更是机体含氮化合物的主要来源。因此,谷氨酰胺在细胞的能量产生和生物合成中有至关重要的作用,对于人体基本无副作用。目前有研究表明,谷氨酰胺代谢可能成为肿瘤治疗的靶点,以及可能在再生医学中发挥更加重要的作用。谷氨酰胺在疾病治疗方面的作用正从不同角度进行开展,但是,以其作为活性成分在治疗银屑病中的应用未见有报道。
本发明的研究人员通过长期研究,根据银屑病皮损面积和严重程度指数(PASI)评分及皮损HE染色,首先发现并证明谷氨酰胺对银屑病有显著的治疗作用,能有效减轻MDSCs细胞群、Th1、Th17细胞群的增多以及Tregs细胞群的减少。本发明给谷氨酰胺提供了新用途,为治疗银屑病提供了一种新的药物。研究表明,谷氨酰胺无论是应用于外用药物还是内用药物,对于治疗银屑病均有明显的药效,应用前景广泛,具有较大的推广应用价值。而且,由于谷氨酰胺是人体内含量最丰富的氨基酸,其对人体的副作用小,也降低了研发成本和制造成本。
附图说明
图1为动物实验一中第一组、第二组、第三组和第四组小鼠第6天的耳部照片;
图2为动物实验一中第一组、第二组、第三组和第四组小鼠耳部皮损的第一天到第六天PASI评分图;
图3为动物实验一中第一组、第二组、第三组和第四组小鼠耳部皮损第六天的HE染色;
图4为动物实验一中第一组、第二组、第三组和第四组小鼠耳部皮损第六天的表皮厚度统计;
图5为动物实验一中第一组、第二组、第三组和第四组小鼠耳部皮肤细胞流式结果图,其中A为单核型MDSCs细胞群检测结果,B为Th1细胞群检测结果,C为Tregs细胞群检测结果;
图6为动物实验二中第一组、第二组和第三组小鼠第6天的背部照片;
图7为动物实验二中第一组、第二组和第三组小鼠背部皮损的第一天到第六天PASI评分图;
图8为动物实验二中第一组、第二组和第三组小鼠背部皮损第六天的HE染色;
图9为动物实验二中第一组、第二组和第三组小鼠背部皮损第六天的表皮厚度统计;
图10为动物实验二中第一组、第二组和第三组小鼠背部皮肤细胞流式结果图,其中A为单核型MDSCs细胞群检测结果,B为Th17细胞群检测结果。
具体实施方式
为了便于理解本发明,下面将对本发明进行更全面的描述,并给出了本发明的较佳实施例。但是,本发明可以以许多不同的形式来实现,并不限于本文所描述的实施例。相反地,提供这些实施例的目的是使对本发明的公开内容的理解更加透彻全面。
除非另有定义,本文所使用的所有的技术和科学术语与属于本发明的技术领域的技术人员通常理解的含义相同。本文中在本发明的说明书中所使用的术语只是为了描述具体的实施例的目的,不是旨在于限制本发明。本文所使用的术语“和/或”包括一个或多个相关的所列项目的任意的和所有的组合。
术语
PASI评分(Psoriasis Area and Severity Index)是综合银屑病患者的皮损严重程度(包括红斑、浸润、鳞屑)及皮损面积对其进行评分。通过特定公式计算出最终分数,常常用来对寻常型银屑病的严重程度进行评估,是国际上通用于银屑病皮损程度的评分标准。
MDSCs是骨髓来源的抑制性细胞(Myeloid-derived suppressor cells)的英文简称,MDSCs来源于骨髓祖细胞和未成熟髓细胞(immature myeloid cells,IMCs)。正常情况下,是树突状细胞(DC)、巨噬细胞和粒细胞的前体,能迅速地分化为成熟的粒细胞、DCs和巨噬细胞,并进入相应的器官、组织,发挥正常免疫功能,IMCs占外周血单个核细胞的0.5%左右。在肿瘤、感染、炎症、败血症、外科损伤等其它病理条件下,受细胞因子的作用,这些髓系来源的前体细胞成熟受阻,因而停留在各个分化阶段,成为具有免疫抑制功能的MDSCs。它们在细胞因子的作用下被募集、迁移、扩增,使得其在外周血中的数量和比例增加10倍左右,约占患者外周血单个核细胞(PBMC)的10%,贯穿疾病发生的整个过程。
Tregs是调节性T细胞(Regulatory cells),一类控制体内自身免疫反应性的T细胞亚群,早期亦称做Suppressor T cells。调节性T细胞可分为天然产生的自然调节性T细胞(n T-regs)和诱导产生的适应性调节性T细胞(a T-regs或iT-regs),如Th3、Tr1,另外尚有CD8 Treg、NKT细胞等,与自身免疫性疾病的***密切,其异常表达可导致自身免疫性疾病。其中Tr1细胞分泌IL-10,Th3细胞分泌TGF-β。
Th1即1型辅助T细胞,主要为对抗细胞内细菌及原虫的免疫反应,其主要为白介素12(IL-12)所驱动诱发,其主要的执行的细胞因子是伽马干扰素(IFN-γ)。Th17即17型辅助T细胞,主要为对抗细胞外细菌及霉菌的免疫反应,其主要为白介素6(IL-6)及TGF-β所驱动诱发,其主要的执行的细胞因子是白介素1(IL-1)白介素6(IL-6)以及TNF-α。
HE染色即苏木精-伊红染色法(hematoxylin-eosin staining),简称HE染色法,石蜡切片技术里常用的染色法之一。苏木精染液为碱性,主要使细胞核内的染色质与胞质内的核酸着紫蓝色;伊红为酸性染料,主要使细胞质和细胞外基质中的成分着红色。HE染色法是组织学、胚胎学、病理学教学与科研中最基本、使用最广泛的技术方法。
本发明的一个方面提供了谷氨酰胺作为活性成分在制备银屑病治疗药物中的应用。
谷氨酰胺是谷氨酸的酰胺,L-谷氨酰胺是蛋白质合成中的编码氨基酸,哺乳动物非必需氨基酸,在体内可以由葡萄糖转变而来,白色结晶或晶性粉末,能溶于水,不溶于甲醇、乙醇、醚、苯、丙酮、氯仿和乙酸乙酯,无臭,稍有甜味。在中性溶液中不稳定,在醇、碱或热水中易分解成谷氨醇或丙酯化为吡咯羧醇,无臭,有微甜味。谷氨酰胺是肌肉中最丰富的游离氨基酸,约占人体游离氨基酸总量的60%,空腹血浆谷氨酰胺浓度为500~750μmol/L,其结构式如下:
除此之外,人们发现谷氨酰胺代谢过程不仅为细胞代谢中提供碳,提供的氮更是机体含氮化合物的主要来源。因此,谷氨酰胺在细胞的能量产生和生物合成中有至关重要的作用,对于人体基本无副作用。目前有研究表明,谷氨酰胺代谢可能成为肿瘤治疗的靶点,以及可能在再生医学中发挥更加重要的作用。谷氨酰胺在疾病治疗方面的作用正从不同角度进行开展,但是,以其作为活性成分在治疗银屑病中的应用未见有报道。
本发明的研究人员通过长期研究,根据银屑病皮损面积和严重程度指数(PASI)评分及皮损HE染色,首先发现并证明谷氨酰胺对银屑病有显著的治疗作用,能有效减轻MDSCs细胞群、Th1、Th17细胞群的增多以及Tregs细胞群的减少。本发明给谷氨酰胺提供了新用途,为治疗银屑病提供了一种新的药物。研究表明,谷氨酰胺无论是应用于外用药物还是内用药物,对于治疗银屑病均有明显的药效,应用前景广泛,具有较大的推广应用价值。而且,由于谷氨酰胺是人体内含量最丰富的氨基酸,其对人体的副作用小,也降低了研发成本和制造成本。
本发明一实施例的银屑病治疗药物,其活性成分主要由谷氨酰胺组成。
在一个具体示例中,银屑病治疗药物的剂型为溶液剂、洗剂、搽剂、软膏剂、硬膏剂、糊剂或贴剂。可以理解,上述银屑病治疗药物可以是外用药物也可以是内用药物,给药方式可以是皮下注射、静脉注射、口服、涂抹等。
在一个具体示例中,银屑病治疗药物的剂型为溶液剂,主要由谷氨酰胺和溶剂组成。
在一个具体示例中,溶剂为生理盐水,但不限于此。
在一个具体示例中,银屑病治疗药物中,谷氨酰胺的浓度为0.02g/mL~2g/mL。可选地,银屑病治疗药物中,谷氨酰胺的浓度为0.04g/mL。可以理解,具体浓度可根据病情或个体情况根据需要调整。
在一个具体示例中,银屑病治疗药物还包括稀释剂、防腐剂、缓冲剂、崩解剂、抗氧剂、助悬剂、着色剂和赋形剂中的一种或多种。
在一个具体示例中,稀释剂选自聚乙二醇、丙二醇、植物油和矿物油中的一种或多种。在一个具体示例中,防腐剂选自山梨酸、山梨酸甲酯、对羟基苯甲酸甲酯、对羟基苯甲酸乙酯、对羟基苯甲酸丙酯、对羟基苯甲酸丁酯、对羟基苯甲酸苄酯、对羟基苯甲酸甲酯钠、苯甲酸和苯甲醇中的一种或多种。在一个具体示例中,缓冲剂选自磷酸氢钠、磷酸二氢钠、枸橼酸钠、酒石酸钠和醋酸钠中的一种或多种。在一个具体示例中,崩解剂选自交联羧甲基纤维素钠、羧甲基淀粉钠、交联聚乙烯吡咯烷酮或低取代羟丙基纤维素中的一种或多种。在一个具体示例中,抗氧剂选自乙二胺四乙酸、乙二胺四乙酸二钠盐、二丁基羟基甲苯、甘氨酸、肌醇、抗坏血酸、抗坏血酸钠、卵磷脂、苹果酸、氢醌、枸橼酸、琥珀酸和焦亚硫酸钠中的一种或多种。在一个具体示例中,助悬剂选自蜂蜡、乙基羟乙基纤维素、甲壳素、甲壳糖、甲基纤维素、羧甲基纤维素、琼脂、羟丙基甲基纤维素和黄原胶中的一种或多种。在一个具体示例中,着色剂选自炭黑、铁黑、铁棕、铁红和二氧化钛中的一种或多种。在一个具体示例中,赋形剂选自甘露醇、葡萄糖、乳糖、葡聚糖、右旋糖苷和氯化钠中的一种或多种。
在一个具体示例中,上述银屑病治疗药物为外用膏剂,例如可为乳膏剂或油膏剂。
在一个具体示例中,银屑病治疗药物主要由基质及作为活性成分的谷氨酰胺制备而成。
在一个具体示例中,上述银屑病治疗药物为油膏剂。进一步地,上述银屑病治疗药物中,基质包括羊毛脂、白凡士林和/或DMSO(二甲基亚砜)。该外用膏剂为油膏状,直接涂覆于患者皮肤表面即可。
在一个具体示例中,上述银屑病治疗药物为乳膏剂。进一步地,上述银屑病治疗药物中,基质包括十八醇、白凡士林、单硬酯酸甘油酯、十二烷基硫酸钠、甘油、对羟基苯甲酸乙酯和水。
本发明一实施例的上述银屑病治疗药物的制备方法,包括如下步骤:将谷氨酰胺与溶剂或基质混合,即可得到上述银屑病治疗药物。可以理解,根据剂型或配方的不同,制备方法可以根据需要调整。
以下为具体实施例。
实施例1
外用制剂制备:将400mg谷氨酰胺溶解于10mL生理盐水中,制得用于治疗银屑病的4%谷氨酰胺生理盐水制剂,装瓶备用。
对比例1
外用制剂制备:将400mg丙氨酸溶解于10mL生理盐水中,制得作为4%谷氨酰胺生理盐水制剂的对照品4%丙氨酸生理盐水制剂,装瓶备用。
对比例2
外用制剂制备:仅用10mL生理盐水,作为4%谷氨酰胺生理盐水制剂的对照品。
实施例2
口服制剂制备:将4g谷氨酰胺溶解于100mL生理盐水中,制得用于治疗银屑病的4%谷氨酰胺生理盐水口服制剂,装瓶备用。
对比例3
口服制剂制备:仅用100mL生理盐水,作为4%谷氨酰胺生理盐水口服制剂的对照品。
以下为动物试验。
咪喹莫特(imiquimod,IMQ)是Toll样受体(Tolllike receptor,TLR)7/8的激动剂,主要用于外阴及肛周疣和光化性角化病的局部治疗。研究发现,将咪喹莫特外涂于小鼠皮肤,可诱导小鼠皮肤出现银屑病样皮损及组织学改变,与人类银屑病病理变化有很多相似之处。咪喹莫特诱导的小鼠模型,能够很好地从皮肤增厚、角质形成细胞相关蛋白异常、炎性细胞浸润及相关炎症细胞因子等方面模拟与人相似的银屑病症状。此种模型由于简单易操作,模型稳定,现已成为研究及应用最广的银屑病模型之一。
动物实验一
取20只SPF级(无特定病原体级实验动物)6~8周的BALB/C小鼠随机分成4组,每组5只。第一组为control组,不做任何处理;第二组为IMQ+Vehicle组,在耳部涂抹咪喹莫特前后半小时滴加20μL对比例2的生理盐水;第三组为IMQ+4%丙氨酸组,在耳部涂抹咪喹莫特前后半小时滴加20μL对比例1的4%丙氨酸生理盐水制剂;第四组为IMQ+4%谷氨酰胺组,在耳部涂抹咪喹莫特前后半小时滴加20μL实施例1的4%谷氨酰胺生理盐水制剂。
每组连续涂药6天后,对各组小鼠耳部皮损进行银屑病皮损面积和严重程度指数(PASI)评分考察小鼠银屑病样症状,然后称重拍照处死小鼠,取耳部皮损做HE染色实验考察表皮的厚度即角质细胞的增殖情况及细胞流式考察银屑病相关免疫细胞的数量变化,并同时取小鼠脾脏称重拍照。
PASI打分原则如下:每日评估皮肤炎症的严重程度,包括测量皮肤厚度、结痂、红斑情况。采用5分制(0~4)分别进行打分:
皮肤厚度:0:皮肤光滑无褶皱;1:涂药区域边缘处皮肤出现轻微褶皱;2:涂药区域皮肤全部出现轻微褶皱;3:涂药区域褶皱程度进一步加深;4:在评分为3的基础上,小鼠出现体重下降或状态欠佳等状况;
结痂:0:皮肤光滑无鳞屑;1:涂药区域皮肤出现轻微鳞屑;2:涂药区域皮肤全部被鳞屑覆盖;3:涂药区域鳞屑程度进一步加深;4:在评分为3的基础上,小鼠出现体重下降或状态欠佳等状况;
红斑:0:皮肤光滑;1:涂药区域皮肤出现轻微红色;2:涂药区域皮肤全部变为红色;3:涂药区域红色进一步加深;4:在评分为3的基础上,小鼠出现体重下降或状态欠佳等状况;
总评分:皮肤厚度、结痂和红斑的三项评分之和。
如图1所示,为第一组、第二组、第三组和第四组小鼠第6天的耳部照片,可见第二组与第一组的耳部皮损相比有明显的红斑、增厚、鳞屑,证明涂抹咪喹莫特后银屑病模型诱导成功。第四组与第二组、第三组相比,可见红斑、浸润、增厚均显著减轻,说明4%谷氨酰胺生理盐水制剂能够有效地治疗银屑病。
如图2所示,为第一组、第二组、第三组和第四组小鼠耳部皮损的第一天到第六天PASI评分图,可见4%谷氨酰胺生理盐水制剂可有效地治疗银屑病。
如图3和图4所示,为第一组、第二组、第三组和第四组小鼠耳部皮损第六天的HE染色及表皮厚度统计图,可见4%谷氨酰胺生理盐水制剂可有效地抑制角质形成细胞增殖。
如图5所示,为第一组、第二组、第三组和第四组小鼠耳部皮肤细胞流式结果图,可见第二组的单核型MDSCs细胞群、Th1细胞群、Th17细胞群数量明显增多以及Tregs细胞群明显减少,而谷氨酰胺能明显抑制IMQ诱导的单核型MDSCs、Th1增多以及Tregs减少。
动物实验二
取11只SPF级(无特定病原体级实验动物)6~8周的BALB/C小鼠随机分成3组,第一组和第二组4只,第三组3只。第一组为control组,不做任何处理;第二组为IMQ+Vehicle组,使用对比例3的生理盐水口服制剂饲喂37天,使用咪喹莫特涂抹背部造模;第三组为IMQ+4%谷氨酰胺组,使用实施例2的4%谷氨酰胺生理盐水口服制剂饲喂37天,使用咪喹莫特涂抹背部造模。
每组连续涂药6天后,对各组小鼠背部皮损进行银屑病皮损面积和严重程度指数(PASI)评分考察小鼠银屑病样症状,然后称重拍照处死小鼠,取耳部皮损做HE染色实验考察表皮的厚度即角质细胞的增殖情况及细胞流式考察银屑病相关免疫细胞的数量变化,并同时取小鼠脾脏称重拍照。
如图6所示,为第一组、第二组和第三组小鼠第6天的背部照片,可见第二组与第一组的背部皮损相比有明显的红斑、增厚、鳞屑,证明涂抹咪喹莫特后银屑病模型诱导成功。第三组与第二组相比,可见红斑、浸润、增厚均显著减轻,说明4%谷氨酰胺生理盐水口服制剂能够有效地治疗银屑病。
如图7所示,为第一组、第二组和第三组小鼠背部皮损的第一天到第六天PASI评分图,可见4%谷氨酰胺生理盐水口服制剂可有效地治疗银屑病。
如图8和图9所示,为第一组、第二组和第三组小鼠背部皮损第六天的HE染色及表皮厚度统计图,可见4%谷氨酰胺生理盐水口服制剂可有效地抑制角质形成细胞增殖。
如图10所示,为第一组、第二组和第三组小鼠背部皮肤细胞流式结果图,可见第二组的单核型MDSCs细胞群、Th1细胞群、Th17细胞群数量明显增多,而谷氨酰胺能明显抑制IMQ诱导的单核型MDSCs、Th17增多。
以上所述实施例的各技术特征可以进行任意的组合,为使描述简洁,未对上述实施例中的各个技术特征所有可能的组合都进行描述,然而,只要这些技术特征的组合不存在矛盾,都应当认为是本说明书记载的范围。
以上所述实施例仅表达了本发明的几种实施方式,其描述较为具体和详细,但并不能因此而理解为对发明专利范围的限制。应当指出的是,对于本领域的普通技术人员来说,在不脱离本发明构思的前提下,还可以做出若干变形和改进,这些都属于本发明的保护范围。因此,本发明专利的保护范围应以所附权利要求为准。
Claims (10)
1.谷氨酰胺作为活性成分在制备银屑病口服治疗药物中的应用。
2.根据权利要求1所述的应用,其特征在于,所述银屑病口服治疗药物的剂型为溶液剂。
3.根据权利要求2所述的应用,其特征在于,所述银屑病口服治疗药物主要由谷氨酰胺和溶剂组成。
4.根据权利要求3所述的应用,其特征在于,所述溶剂为生理盐水。
5.根据权利要求2所述的应用,其特征在于,所述银屑病口服治疗药物中,所述谷氨酰胺的浓度为0.02g/mL~2g/mL。
6.根据权利要求2所述的应用,其特征在于,所述银屑病口服治疗药物中,所述谷氨酰胺的浓度为0.04g/mL。
7.根据权利要求2~6任一项所述的应用,其特征在于,所述银屑病口服治疗药物还包括稀释剂、防腐剂、缓冲剂、抗氧剂、助悬剂和着色剂中的一种或多种。
8.根据权利要求7所述的应用,其特征在于,所述稀释剂选自丙二醇、植物油和矿物油中的一种或多种,所述防腐剂选自山梨酸、山梨酸甲酯、对羟基苯甲酸甲酯、对羟基苯甲酸乙酯、对羟基苯甲酸丙酯、对羟基苯甲酸丁酯、对羟基苯甲酸苄酯、对羟基苯甲酸甲酯钠、苯甲酸和苯甲醇中的一种或多种,所述缓冲剂选自磷酸氢钠、磷酸二氢钠、枸橼酸钠、酒石酸钠和醋酸钠中的一种或多种。
9.根据权利要求7所述的应用,其特征在于,所述抗氧剂选自乙二胺四乙酸、乙二胺四乙酸二钠盐、二丁基羟基甲苯、甘氨酸、肌醇、抗坏血酸、抗坏血酸钠、卵磷脂、苹果酸、氢醌、枸橼酸、琥珀酸和焦亚硫酸钠中的一种或多种,所述助悬剂选自蜂蜡、乙基羟乙基纤维素、甲壳素、甲壳糖、甲基纤维素、羧甲基纤维素、琼脂、羟丙基甲基纤维素和黄原胶中的一种或多种,所述着色剂选自炭黑、铁黑、铁棕、铁红和二氧化钛中的一种或多种。
10.根据权利要求1所述的应用,其特征在于,所述银屑病口服治疗药物的制备方法,包括以下步骤:将谷氨酰胺与溶剂混合,得到所述银屑病口服治疗药物。
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