CN110742880A - Cl419在制备治疗炎性肠病药物中的用途 - Google Patents
Cl419在制备治疗炎性肠病药物中的用途 Download PDFInfo
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Abstract
本发明涉及生物医药领域，具体涉及CL419在制备治疗炎性肠病药物中的用途。
Description
技术领域
本发明涉及生物医药领域，具体涉及CL419在制备治疗炎性肠病药物中的用途。
背景技术
炎性肠病(inflammatory bowel disease，IBD)是以肠道非特异性炎症损伤为特征的慢性复发性疾病，包括溃疡性结肠炎(ulcerative colitis，UC)和克罗恩病(Crohn'sdisease)。通过肠镜检查，可以观察到肠粘膜充血、水肿、颗粒样改变甚至溃疡形成；在组织病理学上病变区域广泛溃疡形成伴有大量中性粒细胞浸润和肠粘膜坏死。然而，炎性肠病的发病机理目前并没有明确的定论，可能与基因易感性、外界环境刺激、自身免疫以及肠道菌群失调有关。
CL419是一种多胺TLR2激动剂，来源于Pam2CSK4，用阳离子精氨酸组取代Ser-(Lys)4。CL419形成带正电荷的脂体，使其变得复杂核酸，并将其输送到细胞醇和细胞核。CL419与核酸的复合物由TLR2和核识别酸性传感器，导致NF-kB和IRF路径显著激活。在体内，CL419与质粒DNA复合(pDNA)和注射在肿瘤内诱导适度减少。
发明内容
本发明要解决的技术问题是：提供一种CL419的新用途。
在本发明的第一方面，提供了CL419或其药学上可接受的盐在制备治疗炎性肠病药物中的用途。
本发明化合物药学上可接受的盐，具体的可列举上述化合物与盐酸、氢溴酸、硫酸、硝酸磷酸等无机酸的盐，与甲酸、乙酸、丙酸、草酸、丙二酸、琥珀酸、富马酸、马来酸、乳酸、苹果酸、酒石酸、柠檬酸、苦味酸、甲磺酸、对甲基苯磺酸等有机酸和天门氨酸、谷氨酸等酸性氨基酸的酸形成的盐。
CL419作为一种TLR2激动剂，其已公开的用途是用于抗肿瘤，发明人意外发现，其具有治疗炎性肠病的新用途。
在本发明的第二方面，提供了一种药物组合物，其含有治疗量的CL419或其药学上可接受的盐及药学上可接受的辅料。
本发明的有益效果在于首次发现并证实了CL419对DSS(葡聚糖硫酸钠)诱导的小鼠肠炎具有良好的治疗效果。
附图说明
图1为对照组(n＝9)与处理组(n＝6)小鼠从口服DSS饮用水后的生存期折线图。
具体实施方式
以下结合实例说明本发明，但不限制本发明。在本领域内，技术人员对本发明所做的简单替换或改进均属于本发明所保护的技术方案内。
材料与方法：
小鼠：雄性野生型C57小鼠(6-8周)购于中国科学院(上海)。所有小鼠均饲养于第二军医大学(上海)动物实验中心无特殊病原体(SPF)实验室。处理组小鼠连续3天给予50ug/ml CL-419(购自上海源溪生物科技有限公司)腹腔注射，后给予1.5％DSS(40,000kDa；ICN Biochemicals)饮用水口服7天后转为正常饮用水。对照组小鼠与处理组小鼠同一时间给予1.5％DSS饮用水口服7天后转为正常饮用水。
生存期实验：记录对照组(n＝9)与处理组(n＝6)小鼠口服DSS饮用水15天后的生存期。附图1显示腹腔注射CL419的处理组小鼠生存期明显好于对照组小鼠。对照组小鼠的平均生存天数是9.2天，CL419的处理组小鼠平均生存天数是11.5天。
以上所述的仅是本发明的优选实施方式，应当指出，对于本领域的普通技术人员来说，在不脱离本发明创造构思的前提下，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。
Claims (2)
1.CL419或其药学上可接受的盐在治疗炎性肠病中的用途。
2.一种药物组合物，其特征在于含有治疗量的CL419或其药学上可接受的盐及药学上可接受的辅料。
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| Application Number | Priority Date | Filing Date | Title |
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| CN201911017309 | 2019-10-24 | ||
| CN2019110173090 | 2019-10-24 |
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| CN110742880A true CN110742880A (zh) | 2020-02-04 |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20130065861A1 (en) * | 2010-03-23 | 2013-03-14 | Irm Llc | Compounds (cystein based lipopeptides) and compositions as tlr2 agonists used for treating infections, inflammations, respiratory diseases etc. |
| EP2769738A1 (en) * | 2013-02-22 | 2014-08-27 | Invivogen | Conjugated TLR7 and/or TLR8 and TLR2 polycationic agonists |
| US20170239347A1 (en) * | 2014-01-24 | 2017-08-24 | Children's Hospital Of Eastern Ontario Research Institute Inc. | Smc combination therapy for the treatment of cancer |
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- 2019-11-14 CN CN201911111832.XA patent/CN110742880A/zh active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20130065861A1 (en) * | 2010-03-23 | 2013-03-14 | Irm Llc | Compounds (cystein based lipopeptides) and compositions as tlr2 agonists used for treating infections, inflammations, respiratory diseases etc. |
| EP2769738A1 (en) * | 2013-02-22 | 2014-08-27 | Invivogen | Conjugated TLR7 and/or TLR8 and TLR2 polycationic agonists |
| US20170239347A1 (en) * | 2014-01-24 | 2017-08-24 | Children's Hospital Of Eastern Ontario Research Institute Inc. | Smc combination therapy for the treatment of cancer |
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