CN112912096A - 用于预防或治疗炎性疾病的药物组合物 - Google Patents
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Abstract
本发明提供了药物组合物，其具有优异的抗炎效果，从而使得能够有效预防或治疗炎性疾病，诸如再灌注损伤、牙周炎、关节炎、压疮炎症、创伤炎症或皮炎，并且提供了用作可用于各种炎性皮肤病的化妆品的原料的抗炎化妆品组合物。
Description
技术领域
本发明涉及用于预防或治疗炎性疾病的具有优异抗炎作用的药物组合物。
背景技术
炎症是身体防止外部物理刺激、化学刺激(例如，各种过敏原的接触)或诸如细菌、真菌或病毒等微生物的入侵对身体组织造成损害的防御反应。
炎症信号通过环氧合酶(COX)途径或脂氧合酶(LOX)途径产生，并产生前列腺素、血栓烷等。当炎症信号传递时，身体会发生各种变化。一种变化是其中血管在需要炎症的区域扩张，从而导致炎症反应所需的血细胞(诸如中性粒细胞)的大量供应的现象。然而，异常过度的身体防御反应可导致各种炎性疾病。为了防止这种现象，正在开发能够通过抑制与炎症信号传导途径相关的酶(例如，COX-1、COX-2、5-LOX、12-LOX等)来阻断炎症信号传导途径，从而遏制过度的炎症反应的药物。
炎症根据反应的持续时间分为急性炎症(即时反应，非特异性反应，数天至数周)、慢性炎症(延迟反应，特异性反应，数周以上)和亚急性炎症(急性炎症和慢性炎症的中间阶段，特征在于多形核细胞和单核细胞的混合产物)。
另外，引起或介导炎症的因子除了肽因子以外，还包括脂质因子诸如前列腺素、白三烯和血小板活化因子、炎症因子合酶、自由基诸如NO(一氧化氮)、各种类型的细胞粘附分子、免疫系统因子和凝血因子。
迄今已知的炎症机制是，细胞损伤是由外部生物因素(细菌、病毒、寄生虫)、物理因素(机械刺激、热、辐射、电)、化学因素等引起的，导致组胺和激肽的释放，然后血管扩张、毛细血管通透性增加以及巨噬细胞向炎症部位聚集，从而导致诸如流向感染部位的血流增加、肿胀、免疫细胞和抗体移动、疼痛和发热等现象。
目前使用的炎症治疗剂包括合成药物，诸如布洛芬、抗组胺药、类固醇、可的松、免疫抑制剂和免疫增强剂，但它们仅具有暂时的治疗效果或仅症状缓解的局限性，或者导致许多副作用，诸如过敏和免疫系统恶化，因此难以用于从根本上治疗炎症。
因此，为了有效缓解炎症，最近对能够抑制炎症相关蛋白表达的物质进行了研究。然而，在作为这种研究的结果而开发的抗炎物质中出现了与副作用相关的问题。已经开发了基于各种机制的用于遏制炎症的药物，包括非甾体抗炎药(NSAID)和甾体抗炎药(SAID)。然而，这些药物都有一定的副作用，并不能从根本上抑制炎症反应，所以仍然需要更加有效、安全和经济的药物。例如，已知用于治疗慢性炎性疾病诸如急性或类风湿性关节炎的非甾体抗炎药通过抑制COX-2酶以及COX-1酶而引起诸如胃肠病症的副作用。
公开内容
技术问题
本发明的一个目的是提供具有优异抗炎效果的药物组合物和化妆品组合物。
技术解决方案
根据本发明的一个方面，上述和其它目的可通过提供用于预防或治疗炎性疾病的药物组合物来实现，所述药物组合物包含由SEQ ID NO:1的序列组成的多肽。
炎性疾病可包括至少一种选自神经炎症、再灌注损伤、牙周炎、关节炎、皮炎、创伤炎症、褥疮炎症、脊椎炎、尿道炎、膀胱炎、肾炎、肾盂肾炎、脉管炎、鼻炎、咽喉痛、扁桃体炎、急性疼痛和炎性肠病的炎性疾病。
根据本发明的另一方面，提供了抗炎化妆品组合物，其包含由SEQ ID NO:1的序列组成的多肽。
有利效果
本发明提供了有效地预防或治疗炎性疾病诸如再灌注损伤、牙周炎、关节炎或皮炎的具有优异抗炎效果的药物组合物，并且提供了用作用于各种炎性皮肤病的化妆品的原料的抗炎化妆品组合物。
附图说明
图1显示了在实施例1中比较未处理的对照组、仅用LPS处理的对照组、用本发明的肽和LPS一起处理的实验组和仅用本发明的肽处理的实验组之间的TNF-α表达水平的数据。
图2显示了实施例2中单独用PBS处理的对照组与用LPS和本发明的肽的组合处理的组之间的IL-8、CXCL1和CXCL10的表达水平。
图3是显示实施例3中用于免疫组织化学(IHC)的染色的心脏组织部位的示意图。
图4显示了实施例3中测量组1至组4中的eNOS表达水平的结果。
图5显示了实施例3中测量组1至组4中的TNF-α表达水平的结果。
图6显示了实施例3中测量组1至组4中的CD68(巨噬细胞)表达水平的结果。
图7显示了实施例3中测量组1至组4中的Ly-6B(中性粒细胞)表达水平的结果。
图8显示了实施例4中通过观察结扎后、再灌注后和生产后繁殖期期间的一般症状来测定每组的存活概率的结果。
图9和图10显示了实施例4中使用超声心动描记术测量EF和FS值的结果。
图11显示了实施例4中测量心肌组织的梗塞面积和纤维化程度的结果。
详细描述和示例性实施方案
在下文中，将详细描述本发明。
本发明提供了用于预防或治疗炎性疾病的药物组合物，其包含由SEQ ID NO:1的序列组成的多肽。
如本文中所用，术语“治疗”是指获得有益或期望的临床结果的方法。就本发明而言，有益或期望的临床结果包括但不限于症状的缓解、疾病范围的缩小、疾病状况的稳定(即，阻止恶化)、疾病进展的延迟或减缓、疾病状况的改善或暂时缓解和缓解(部分或全部)，以及是否可以检测到。另外，术语“治疗”可以指与未接受治疗时预期的存活概率相比，增加存活概率。治疗涵盖治疗性治疗和预防性措施。这种治疗包括预防病症所需的治疗和已经发展的病症所需的治疗。
如本文中所用，术语“预防”是指遏制或延迟相关疾病发作的任何行动。对于本领域技术人员显而易见的是，当在疾病的初始症状或发作之前施用时，本发明的组合物可预防相关疾病。
由SEQ ID NO:1的序列组成的多肽具有优异的抗炎功效。例如，所述多肽有效地降低了被称为炎症症标志物的eNOS、TNF-α、CD68和Ly-6B(中性粒细胞)的表达水平，从而表现出预防或治疗各种炎性疾病的效果。
本发明的多肽可以化学合成。当通过化学合成制备多肽时，其可通过本领域中公知的化学合成(Creighton,Proteins；Structures and Molecular Principles,W.H.Freeman和Co.,NY,1983)来制备。代表性方法包括但不限于液相或固相合成、片段缩合、F-MOC或T-BOC化学方法(肽和蛋白质合成的化学方法(Chemical Approaches to theSynthesis of Peptides and Proteins,Williams等人，编辑，CRC Press,Boca RatonFlorida,1997；A Practical Approach,Atherton&Sheppard，编辑，IRL Press,Oxford,England,1989)。
另外，本发明的多肽可通过基因工程方法(诸如以下方法，但不限于此)制备。首先，根据常规方法产生编码多肽的DNA序列。DNA序列可通过使用合适的引物进行PCR扩增来产生。或者，还可通过本领域已知的标准方法，例如，使用自动DNA合成仪(例如，由Biosearch or Applied Biosystems出售的)合成DNA序列。将产生的DNA序列插入含有一个或多个表达控制序列(例如，启动子、增强子等)的载体中，所述表达控制序列可操作地连接于所述DNA序列并控制所述DNA序列的表达，并用所得重组表达载体转化宿主细胞。将所得转化体在适于允许DNA序列表达的培养基和条件下进行培养，以及从培养产物中回收由DNA序列编码的基本上纯的多肽。可使用本领域已知的方法(例如，色谱)进行回收。上述术语“基本上纯的多肽”意指根据本发明的多肽基本上不含任何其它来源于宿主的蛋白质。关于用于合成本发明的多肽的基因工程方法，可以参考以下文献“Maniatis等人，MolecularCloning；A laboratory Manual,Cold Spring Harbor laboratory,1982；Sambrook等人，Molecular Cloning:A Laboratory Manual,ColdSpring Harbor Press,N.Y.,第二版(1998)和第三版(2000)；Gene Expression Technology,Method in Enzymology,Geneticsand Molecular Biology,Method in Enzymology,Guthrie&Fink(编辑),Academic Press,San Diego,Calif,1991；以及Hitzeman等人，J.Biol.Chem.,255:12073-12080,1990。
所述药物组合物可以按照常规方法进行配制并以诸如粉剂、颗粒剂、片剂、胶囊、混悬剂、乳剂、糖浆剂或气雾剂、外用制剂、栓剂或无菌注射溶液等的口服制剂的形式使用，但不限于此。
可以包含在含有根据本发明的多肽的药物组合物中的载体、赋形剂或稀释剂可包括但不限于乳糖、葡萄糖、蔗糖、糊精、麦芽糖糊精、山梨醇、甘露醇、木糖醇、赤藓糖醇、麦芽糖醇、淀粉、阿拉伯胶、藻酸盐、明胶、磷酸钙、硅酸钙、纤维素、甲基纤维素、微晶纤维素、聚乙烯吡咯烷酮、水、羟基苯甲酸甲酯、羟基苯甲酸丙酯、滑石、硬脂酸镁和矿物油。在制剂的情况下，使用通常使用的稀释剂或赋形剂，诸如填充剂、增量剂、粘合剂、润湿剂、崩解剂或表面活性剂，但不限于此。
口服施用的固体制剂可包括但不限于片剂、丸剂、粉剂、颗粒剂、胶囊剂等，固体制剂可通过混合至少一种赋形剂，例如淀粉、碳酸钙、蔗糖、乳糖、明胶等来制备。除了简单的赋形剂以外，还使用润滑剂，诸如硬脂酸镁和滑石。
用于口服施用的液体制剂可以是混悬剂、口服液和溶液、乳液、糖浆剂等，并且除了水和液体石蜡以外，还可包括各种赋形剂，诸如润湿剂、甜味剂、芳香剂、防腐剂等，水和液体石蜡是常用的简单稀释剂。用于肠胃外施用的制剂可以是无菌水溶液、非水溶液、混悬剂、乳液、冻干制剂和栓剂。非水溶液和混悬剂的实例包括丙二醇、聚乙二醇、植物油诸如橄榄油、可注射的酯诸如油酸乙酯等。栓剂基质的实例包括威特普索(Witepsol)、聚乙二醇(macrogol)、Tween 61、可可脂、月桂脂(laurin butter)、甘油明胶等。
本发明的组合物用作抗炎剂，可用于预防和治疗炎性疾病，诸如创伤炎症、褥疮炎症、皮炎(包括特应性皮炎)、神经炎、脊椎炎、尿道炎、膀胱炎、肾炎、肾盂肾炎、脉管炎、鼻炎、牙周炎、关节炎、咽喉痛、扁桃体炎、急性疼痛、再灌注损伤或炎性肠病。任何炎性疾病都可以使用，没有特别的限制。
本发明还提供了抗炎化妆品组合物，其包含由SEQ ID NO:1的序列组成的多肽。
当本发明的组合物被制备成化妆品组合物时，除了多肽以外，本发明的组合物还可包含化妆品组合物中常用的组分，诸如常规佐剂，诸如抗氧化剂、稳定剂、增溶剂、维生素、色素和芳香剂以及载体。
可加入该组合物的产品的实例包括但不限于化妆品，诸如收敛剂、柔肤水、营养乳液、各种面霜、精华、包装和粉底，以及清洁剂、洗面奶、肥皂、护理剂、美容乳液等。
本发明的化妆品组合物的具体制剂包括诸如皮肤洗剂、皮肤软化剂、皮肤爽肤水、收敛剂、洗剂、乳液、保湿洗剂、营养洗剂、按摩霜、营养霜、保湿霜、护手霜、精华、营养精华、包装、肥皂、香波、清洁泡沫、清洁洗剂、清洁霜、身体洗剂、身体清洁剂、乳液、口红、隔离霜(makeup base)、粉底、粉饼(press powder)、散粉和眼影等制剂。
可通过将多肽掺入纳米脂质体中来稳定多肽，从而配制组合物。当多肽被包含在纳米脂质体中时，多肽的成分得以稳定，在配制过程中可以解决诸如沉淀和转化等问题，组分的溶解度和透皮吸收可得以增加，并且可以最大化多肽的预期功效。
本发明还提供了抗炎保健功能食品，其包含由SEQ ID NO:1的序列组成的多肽。
本发明的保健功能食品可被生产和加工成片剂、胶囊剂、粉剂、颗粒剂、液体、丸剂等形式，用于抗氧化或抗炎目的。
本发明的保健功能食品是指根据第6727号保健功能食品法，使用对人体具有有用功能的原料或成分生产和加工的食品。健康功能食品是为了控制营养物或获得有益于健康的效果，诸如关于人体结构和功能的生理效果而服用的物质。
除非另有说明，否则本发明的保健功能食品可包含普通食品添加剂，并且根据食品和药物管理局批准的食品添加剂法规的一般规则和一般测试方法，基于目标项目的规范和标准来确定食品添加剂是否合适。
食品添加剂规则中列出的条款的实例包括但不限于化学合成化合物，诸如酮、甘氨酸、柠檬酸钙、烟酸和肉桂酸，天然添加剂，诸如柿子色素、甘草提取物、结晶纤维素、高梁色素和瓜尔胶，以及混合试剂，诸如L-谷氨酸钠、面条碱性添加剂、防腐剂和焦油色素。
例如，可通过将通过常规方法将多肽与赋形剂、粘合剂、崩解剂和其它添加剂混合得到的混合物造粒，向其中加入润滑剂，然后进行压缩成型，或者直接对混合物进行压缩成型，来生产片剂型保健功能食品。另外，根据需要，片剂型保健功能食品可以含有香料等。
在胶囊型保健功能食品当中，硬胶囊可通过用多肽和添加剂诸如赋形剂的混合物填充常规硬胶囊基质来制备，软胶囊可通过用多肽和添加剂诸如赋形剂的混合物填充胶囊基质诸如明胶来制备。如果需要，软胶囊可以包含增塑剂诸如甘油或山梨醇、着色剂、防腐剂等。
丸剂型保健功能食品可通过常规已知方法将多肽与赋形剂、粘合剂、崩解剂等的混合物成型来制备，并且可根据需要用白糖或另一种包衣剂进行包衣，或者还可用诸如淀粉或滑石等材料进行表面包衣。
颗粒型保健功能食品可通过常规已知方法使用多肽与赋形剂、粘合剂、崩解剂等的混合物制备成颗粒形式，并且如果需要，可包含香料、调味剂等。
保健功能食品的实例包括饮料、肉、巧克力、食品、糕饼(confectionery)、比萨饼、拉面、其它面条、口香糖、糖果、冰淇淋、酒精饮料、维生素复合物、健康补充剂等。
在下文中，将参考实施例详细描述本发明。
在下文中，由SEQ ID NO:1的序列组成的肽可以缩写为“本发明的肽”。
实施例1：TNF-α表达抑制能力的测定
(1)实验方法
将培养中的THP-1(人单核细胞系)细胞用本发明的肽(F1701)预处理30分钟，然后用LPS(1μg/mL)处理，接下来让反应进行24小时。反应后，收集培养基，除去剩余的细胞，使用
ELISA人TNF-α(DY210-05,R&D Systems)测量TNF-α的表达水平。
(2)实验结果
可从图1看到未处理对照组、仅用LPS处理的对照组、用本发明的肽连同LPS一起处理的实验组和仅用本发明的肽处理的实验组之间的TNF-α表达水平的比较数据。如可从图1看到的，与未处理的对照组相比，单独用本发明的肽处理可以更有效地抑制TNF-α的表达，并且与仅用LPS处理的对照组不同，用LPS连同本发明的肽一起处理可以以浓度依赖性方式有效地抑制TNF-α的表达。这被认为是有意义的实验结果，表明通过使用本发明的肽抑制炎性疾病标志物的表达，可以获得对各种炎性疾病的治疗效果以及预防效果。
实施例2：IL-8、CXCL1和CXCL10表达水平的控制能力的测定
(1)实验方法
将培养中的THP-1(人单核细胞系)以1.0Х106/孔接种在24孔板中，并培养16小时。用最终浓度为100nM的本发明的肽(F1701)预处理THP-1细胞30分钟，然后用LPS(1μg/mL)处理并培养24小时。通过收集培养基，通过离心除去剩余细胞，然后仅使用上清液来进行样品制备。使用Proteome Profiler Human Cytokine Array试剂盒(R&D)系统比较处理前后细胞因子的表达水平。
(2)实验结果
单独用LPS处理的对照组和用LPS连同本发明的肽一起处理的组中的IL-8、CXCL1和CXCL10的表达水平可以从图2中看到。从图2中看到，与对照组相比，用本发明的肽处理的组表现出降低的IL-8表达水平以及升高的CXCL1和CXCL10表达水平。这被认为是证明本发明的肽降低了作为炎症标志物的IL-8的表达水平，并升高了CXCL1和CXCL10的表达水平，从而激活了愈合伤口的机制的数据，并且被当作鉴定本发明的肽可有效预防或治疗炎性疾病和愈合各种伤口的有意义的结果。
实施例3：对再灌注损伤相关标记基因的表达水平的抑制活性的评价
(1)实验方法
1)实验系统和测试组
将雄性Sprague-Dawley(SD)大鼠用作体内实验的对象，并使用176块心脏组织。其中，用于IHC的染色的心脏组织部位是图3的示意图中的部位2和部位3。
制作石蜡块和切片作为实验组，所有实验组在结扎后用本发明的肽处理一次，并在再灌注后处理一次(通常总共两次)。具体实验组信息示于下表1。
[表1]
2)实验方法
使用心脏组织切片进行免疫组织化学(IHC)。使用切片扫描仪对组织成像，并使用Leica应用套件中的程序测量表达区域的大小，以分析表达率。
3)统计分析
疗效评价的结果是通过比较实验组之间计算的平均值和标准偏差获得的。所使用的统计方法是单因素方差分析检验，并在此基础上确定组间的显著性。数据表示为平均值±SD。在p<0.05的情况下，测试项目的结果被认为是显著的，并且本文使用的用于统计的计算机程序是SPSS 23(IBM,USA)。
(2)实验结果
1)eNOS表达水平的测量
可从图4中看到组1至组4中eNOS表达水平的测量结果。可以看出，与对照组相比，在用本发明的肽处理的所有组中，eNOS的表达水平降低。特别地，与对照组相比，组4显示eNOS的表达水平降低了一半以上。这意味着本发明的肽通过降低心肌中eNOS的表达水平从而抑制心肌功能障碍而有效地预防或治疗再灌注损伤。
2)TNF-α表达水平的测量
可从5中看到组1至组4中TNF-α表达水平的测量结果。可以看出，与对照组相比，在用本发明的肽处理的组中TNF-α的表达水平降低。特别地，与对照组相比，组2至组4显示出约为25％的TNF-α表达水平的降低。这意味着本发明的肽通过降低心肌中TNF-α的表达水平，从而防止进展至炎症反应，来有效地预防或治疗再灌注损伤。
3)CD68表达水平的测量
可从图6中看到组1至组4中CD68(巨噬细胞)表达水平的测量结果。可以看出，与对照组相比，用本发明的肽处理的所有组中CD68的表达水平均显著降低。特别地，与对照组相比，组2和组4表现出约25％的CD68表达水平降低。这意味着本发明的肽通过降低心肌中CD68的表达水平并因此促进抗炎作用而有效地预防或治疗再灌注损伤。
4)LY-6B表达水平的测定
可从图7中看到组1至4组中LY-6B(中性粒细胞)表达水平的测量结果。可以看出，与对照组相比，在用本发明的肽处理的所有组中，LY-6B的表达水平均显著降低。特别地，与对照组相比，组2和组4表现出约40％的LY-6B表达水平降低。这意味着本发明的肽通过降低LY-6B在心肌中的表达水平并因此促进抗炎作用而有效地预防或治疗再灌注损伤。
实施例4：改善心脏功能对抑制再灌注损伤的效果评价
(1)实验方法
作为体内实验的受试者，使用147只广泛用于心血管疾病疗效评价的雄性Sprague-Dawley(SD)大鼠(7周龄，270-320g)。如下面的表2所示，在产生MI/R模型后，向每个组施用对照物质和测试物质。将所述物质在结扎后立即皮下施用一次，再灌注后立即施用一次，总共施用两次。从模型产生后1天开始，在股骨部位和颈背进行皮下施用。
[表2]
为了确定左心室的功能，在产生MI/R模型之前以及在产生MI/R模型之后的第6天和第14天，使用超声心动描记术测量EF和FS值，并且在产生模型之后的第14天，产生心脏组织切片并进行IHC。在模型产生后的第6天和第14天，通过使用Vevo-2100 VisualSonics,CAN)仪器测量射血因子(EF)和缩短分数(FS)来进行超声心动描记术。对于IHC，用切片扫描仪对心脏组织进行成像，表达区域的大小用Leica应用套件程序测量，以分析表达率。使用改进的马森氏三色染色试剂盒测量心脏梗塞面积，使用Leica应用套件程序(Leica,DEU)测量心脏面积和MI面积的大小，以分析MI的比率。疗效评价的结果是通过比较实验组之间计算的平均值和标准偏差获得的。所用的统计方法是单因素差分析检验，并在此基础上确定组间的显著性。数据表示为平均值±SD。在p<0.05的情况下，在缺血性急性心肌梗塞模型中确定本发明的肽的临床剂量的功效评估被认为是显著的，并且本文使用的用于统计的计算机程序是SPSS 23(IBM,USA)。
(2)实验结果
1)生存概率
参考图8，每个组的存活概率可通过观察结扎后、再灌注后和生产后繁殖期期间的一般症状来确定。在实验期期间施用了本发明的肽的所有组(组3至组7)的存活概率在第3天之前为80％或更高，这远高于实验对照组(组2)的存活概率，在所述实验对照组中存活概率在第2天降至75％。特别地，可以看出，组6的存活概率比另外的组高得多，甚至在第14天也保持了超过80％的高存活概率。这表明在用高浓度的本发明的肽治疗时抑制再灌注损伤的能力优于另外的组的情况。
2)使用超声心动描记术评价左心室功能
在产生MI/R模型之前和产生模型之后6天和14天使用超声心动描记术测量EF和FS值以评估左心室功能的结果可以从下面的表3中确定。可以看出，所有实验对照组(组3至组7)的EF和FS均高于对照组(即组2)。特别地，可以看出，组5至组7表现出比对照实验组高得多的EF和FS值。上述结果表明，用本发明的肽治疗可遏制再灌注损伤，并且可以非常有效地抑制对左心室收缩功能的损伤。图9和图10是显示下表3中所示的结果的图表(*p<0.005,**p<0.001,***p<0.0005,****p<0.0001对比G1),(+p<0.005,++p<0.001,+++p<0.0005,++++p<0.0001对比G2),(#p<0.05,#p<0.005对比G3),(§p<0.05对比G4)。
[表3]
3)梗塞面积评估
如从下面的表4可看到的，为了测量心肌组织的梗塞面积和纤维化程度，在产生MI/R模型后的第14天切取心脏，进行马森氏三色(MT)染色，为每个受试者制作5张切片，计算梗塞面积与左心室总面积的比率，并获得平均值。可以看出，与实验对照组(即组2)相比，所有实验组(组3至组7)中的平均梗塞面积比较低。特别地，可以看出组5至组7表现出比实验对照组低得多的平均梗塞面积比。上述结果表明，用本发明的肽进行的治疗，通过抑制再灌注引起的心肌组织梗塞，具有预防或治疗再灌注损伤的显著效果。图11是显示下表4所示的结果的图表(*p<0.05,**p<0.01,***p<0.005对比G2)。
[表4]
| 组 | 第14天左心室的梗塞面积/总面积(％) |
| G2 | 14.3±4.5 |
| G3 | 13.6±4.3 |
| G4 | 11.9±6.0 |
| G5 | 9.5±4.3 |
| G6 | 9.1±5.1 |
| G7 | 9.3±3.9 |
序列表
<110> 艾金株式会社
<120> 用于预防或治疗炎性疾病的药物组合物
<130> 0165-PA-007CN
<150> KR 10-2018-0124897
<151> 2018-10-19
<160> 1
<170> PatentIn version 3.5
<210> 1
<211> 58
<212> PRT
<213> 人工序列（Artificial Sequence）
<220>
<223> 多肽序列 1
<400> 1
Thr Cys Gln Leu Arg Pro Gly Ala Gln Cys Ala Ser Asp Gly Pro Cys
1 5 10 15
Cys Gln Asn Cys Gln Leu Arg Pro Ser Gly Trp Gln Cys Arg Pro Thr
20 25 30
Arg Gly Asp Cys Asp Leu Pro Glu Phe Cys Pro Gly Asp Ser Ser Gln
35 40 45
Cys Pro Pro Asp Val Ser Leu Gly Asp Gly
50 55
Claims (3)
1.一种用于预防或治疗炎性疾病的药物组合物，其包含由SEQ ID NO:1的序列组成的多肽。
2.根据权利要求1所述的药物组合物，其中所述炎性疾病包括选自下组的至少一种：神经炎症、再灌注损伤、牙周炎、关节炎、皮炎、创伤炎症、褥疮炎症、脊椎炎、尿道炎、膀胱炎、肾炎、肾盂肾炎、脉管炎、鼻炎、咽喉痛、扁桃体炎、急性疼痛和炎性肠病。
3.一种抗炎化妆品组合物，其包含由SEQ ID NO:1的序列组成的多肽。
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| KR10-2018-0124897 | 2018-10-19 | ||
| PCT/KR2019/013625 WO2020080836A1 (ko) | 2018-10-19 | 2019-10-17 | 염증성 질환의 예방 또는 치료용 약학적 조성물 |
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| EP (1) | EP3868392A4 (zh) |
| JP (1) | JP2022513370A (zh) |
| KR (1) | KR20200044321A (zh) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101379082A (zh) * | 2006-01-19 | 2009-03-04 | 爱吉恩公司 | 治疗血管相关疾病的包含肽的药物组合物 |
| CN102294016A (zh) * | 2006-01-19 | 2011-12-28 | 爱吉恩公司 | 治疗血管相关疾病的包含肽的药物组合物 |
| CN102482324A (zh) * | 2009-06-15 | 2012-05-30 | 拜欧肯疗法有限公司 | 能够抑制自身免疫、炎症和癌症进程的新型趋化因子结合多肽 |
| CN104168909A (zh) * | 2012-03-12 | 2014-11-26 | 艾金株式会社 | 动脉硬化预防或治疗用药剂学组合物 |
| CN107206047A (zh) * | 2014-12-31 | 2017-09-26 | 汇恩斯株式会社 | 治疗烧伤和青光眼、减少皮肤皱纹和促进毛发生长的包含含rgd基序的肽或其片段的组合物 |
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| DE60127656T2 (de) * | 2000-02-25 | 2007-12-20 | Immunex Corp., Seattle | Integrin antagonisten |
| US9101581B2 (en) * | 2008-10-27 | 2015-08-11 | Eyegene Inc. | Method for treating vascular-related disease |
| US20160086864A1 (en) | 2014-09-24 | 2016-03-24 | Lam Research Corporation | Movable gas nozzle in drying module |
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2018
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- 2019-10-17 CN CN201980068514.1A patent/CN112912096A/zh active Pending
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Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101379082A (zh) * | 2006-01-19 | 2009-03-04 | 爱吉恩公司 | 治疗血管相关疾病的包含肽的药物组合物 |
| CN102294016A (zh) * | 2006-01-19 | 2011-12-28 | 爱吉恩公司 | 治疗血管相关疾病的包含肽的药物组合物 |
| CN102482324A (zh) * | 2009-06-15 | 2012-05-30 | 拜欧肯疗法有限公司 | 能够抑制自身免疫、炎症和癌症进程的新型趋化因子结合多肽 |
| CN104168909A (zh) * | 2012-03-12 | 2014-11-26 | 艾金株式会社 | 动脉硬化预防或治疗用药剂学组合物 |
| CN107206047A (zh) * | 2014-12-31 | 2017-09-26 | 汇恩斯株式会社 | 治疗烧伤和青光眼、减少皮肤皱纹和促进毛发生长的包含含rgd基序的肽或其片段的组合物 |
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| EP3868392A1 (en) | 2021-08-25 |
| JP2022513370A (ja) | 2022-02-07 |
| US20210353711A1 (en) | 2021-11-18 |
| WO2020080836A1 (ko) | 2020-04-23 |
| EP3868392A4 (en) | 2022-07-06 |
| KR20200044321A (ko) | 2020-04-29 |
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