CN117357629A - 一种多肽在制备治疗银屑病中的用途 - Google Patents
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Abstract
本发明属于生物医药技术领域，具体涉及一种多肽在制备治疗银屑病药物中的用途，所述多肽由SEQ ID NO:1所示序列构成，经临床试验功效验证，本发明多肽能够显著降低银屑病患者的PASI评分，显著降低银屑病患者中炎性因子的表达水平，并且对肾功能无明显影响，治疗总有效率高达90％以上。
Description
技术领域
本发明属于生物医药技术领域。更具体地，涉及一种多肽在制备治疗银屑病合并中的用途。
背景技术
银屑病是一种T细胞介导的慢性炎症性疾病，其临床症状主要表现为边界清楚的红斑、丘疹、斑块和鳞屑等，表皮和真皮中炎症细胞浸润，如T淋巴细胞、巨噬细胞和中性粒细胞等。尽管银屑病临床表现明确，但确切病因和发病机制尚不明确。现有研究认为银屑病与遗传、感染、代谢障碍、内分泌紊乱和免疫失调等因素均有关。
氨基酸序列为HGEGTFTSDSEAFIWLGR的多肽已被证实具有胰高血糖素样肽-1(GLP-1)的性质，具有降血糖、增加血浆胰岛素等作用，但目前尚未公开其在治疗银屑病中的用途。
发明内容
发明人意外发现，氨基酸序列为HGEGTFTSDSEAFIWLGR(如SEQ ID NO:1所示)的多肽可明显改善银屑病患者的皮损情况，且引起的肾毒性较小，其主要机制可能与通过激活AMPK从而抑制角质形成细胞的增殖与迁移，降低炎症因子的表达有关。
本发明一方面在于提供氨基酸序列为HGEGTFTSDSEAFIWLGR(如SEQ ID NO:1所示)的多肽在制备治疗银屑病中的用途。研究发现，该多肽能够显著改善银屑病患者皮损积分，经本发明多肽治疗4周后，患者PASI评分与治疗前相比显著降低(P＜0.01)。
试验结果显示，氨基酸序列为HGEGTFTSDSEAFIWLGR(如SEQ ID NO:1所示)的多肽还能显著降低银屑病患者血清中炎症因子(TNF-α、IL-23、IL-6、IFN-γ)的水平，减轻机体炎性反应，改善皮肤损害情况。试验结果显示：经本发明多肽治疗4周后，患者血清中炎性因子的表达极显著下降，与治疗前相比存在极显著差异(P＜0.01)。
试验结果显示，给与本发明多肽治疗的患者观察到的肾毒性更低，各组患者经多肽治疗4周后，各组患者血清中尿素、肌酐及尿酸含量均在参考区间范围内，提示肾功能正常，显示本发明多肽对银屑病患者不产生肾毒性。
因此，本发明另一方面在于提供一种治疗银屑病药物，包含氨基酸序列如SEQ IDNO:1所示的多肽。所述药物可被制成口服给药制剂或者注射给药制剂。
在一些实施方式中，口服给药制剂包括例如颗粒剂、片剂、悬浮液、胶囊或粉剂。这类口服制剂除了包含本发明多肽外，还可包含医药学上可接受的助剂，比如乳化剂、分散剂、粘结剂、甜味剂或者增稠剂等。
在一些实施方式中，注射给药制剂可制备成无菌生理盐水溶剂，除此之外，还可包含其他合适的添加剂。
在一些实施方式中，为了获得治疗效果的最大化，所述药物中，多肽也可作为唯一或主要的活性成分存在。
本发明具有以下有益效果：
经临床试验功效验证，本发明多肽能够显著降低银屑病患者PASI评分，显著降低银屑病患者中炎性因子的表达水平，并且对肾功能无明显影响，治疗总有效率高达90％以上，最高达到95％。
具体实施方式
以下结合具体实施例来进一步说明本发明，但实施例并不对本发明做任何形式的限定。除非特别说明，本发明采用的试剂、方法和设备为本技术领域常规试剂、方法和设备。
除非特别说明，以下实施例所用试剂和材料均为市购。
研究1、临床疗效评价
1资料与方法
1.1一般资料
按照下述纳入标准和排除标准选取129例银屑病患者，平均年龄42.35±5.16岁，平均病程4.48±1.23年，将患者随机分为多肽低剂量组、多肽中剂量组和多肽高剂量组，各组患者一般资料比较无明显差异。
(1)纳入标准：①符合银屑病诊断标准；②病程＞6个月；③患者自愿。
(2)排除标准：①合并其他类型皮肤病；②合并心、肝、肾功能不全者；③合并自身免疫系统疾病或者恶性肿瘤者；④处于妊娠期或者哺乳期。
1.2治疗方法
多肽高中低剂量组分别给予皮下注射50ng/kg/次、25ng/kg/次和10ng/kg/次，每天注射1次，连续注射4周后观察其治疗效果。
1.3观察指标
(1)PASI评分：采用皮损面积严重程度指数PASI对各组患者治疗前后的皮损情况进行评估，评分越高提示患者的皮损情况越严重。
(2)临床疗效：①痊愈：患者临床症状或体征完全消失，皮损完全消退，PASI评分减少超过90％；②显效：患者的临床症状和皮损明显改善，PASI评分减少超过60％；③有效：患者的临床症状和皮损有所改善，PASI评分减少超过30％；④无效：患者症状无变化，PASI评分无减少。
总有效率＝(总例数-无效例数)/总例数×100％。
(3)炎症因子：治疗后采集各组患者空腹状态下静脉血，离心后取上清液，采用酶联免疫吸附法检测血清中TNF-α、IL-23、IL-6、IFN-γ的水平，并且与健康对照组相比。
(4)肾毒性：治疗后采集各组患者静脉血，离心后取上清液，检测血清中尿素(尿素酶法)、肌酐(酶法)及尿酸(尿酸酶法)的水平，取平均值。
1.4统计学方法采用SPSS统计软件对试验数据进行分析，计量资料采用 采用独立样本t检验，P＜0.05时差异具有统计学意义。
2结果
2.1各组患者PASI评分比较治疗4周后，经注射高中低剂量多肽治疗后，各组患者PASI评分均明显下降，各组患者PASI评分显著低于治疗前(P＜0.01)，见表1。
表1各组患者PASI评分比较(分)
注：与治疗前相比，#P＜0.05，##P＜0.01。
2.2各组患者临床疗效比较各剂量组患者总有效率均在90％以上，见表2。
表2各组患者临床疗效比较(n/％)
2.3各组患者血清炎症因子水平比较不同银屑病患者其血清中TNF-α、IL-23、IL-6、IFN-γ因子的表达水平可能存在一定的差异，但各组患者经治疗后血清中炎性因子的表达水平与治疗前相比均存在极显著的下降(P＜0.01)。
表3各组患者血清炎症因子水平
与治疗前相比，#P＜0.05，##P＜0.01。
2.4各组患者肾毒性情况比较各组患者经多肽治疗4周后，各组患者血清中尿素、肌酐及尿酸含量均在参考区间范围内，提示肾功能正常，显示本发明多肽对银屑病患者不产生肾毒性。
注：健康人群血清中尿素、肌酐及尿酸含量参考区间分别为2.6～7.5mmlo/L、41～73μmol/L和150～360μmol/L。
上述实施例为本发明较佳的实施方式，但本发明的实施方式并不受上述实施例的限制，其他的任何未背离本发明的精神实质与原理下所作的改变、修饰、替代、组合、简化，均应为等效的置换方式，都包含在本发明的保护范围之内。
Claims (5)
1.多肽在制备治疗银屑病药物中的用途，其特征在于，所述多肽由SEQ ID NO:1所示序列构成。
2.一种治疗银屑病的药物，其特征在于，包含由SEQ ID NO:1所示序列构成的多肽。
3.根据权利要求2所述药物，其特征在于，所述药物中，多肽作为唯一或主要的活性成分存在。
4.根据权利要求2或3所述药物，其特征在于，所述药物还可包含医药学上可接受的助剂。
5.根据权利要求2或3所述药物，其特征在于，所述药物通过口服给药或者注射给药。
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