CN114712355A - Rhps4在制备抑制人类病原菌药物中的应用及其药物 - Google Patents
Rhps4在制备抑制人类病原菌药物中的应用及其药物 Download PDFInfo
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Abstract
本发明公开了RHPS4在制备抑制人类病原菌药物中的应用，所述RHPS4的全称为3,11‑二氟‑6,8,13‑三甲基‑8H‑喹啉并[4,3,2‑kl]吖啶鎓硫酸甲酯盐；本发明还公开了一种抑制人类病原菌的药物，所述药物的活性成分包括3,11‑二氟‑6,8,13‑三甲基‑8H‑喹啉并[4,3,2‑kl]吖啶鎓硫酸甲酯盐。3,11‑二氟‑6,8,13‑三甲基‑8H‑喹啉并[4,3,2‑kl]吖啶鎓硫酸甲酯盐能够有效抑制金黄色葡萄球菌和和铜绿假单胞菌的生长。
Description
技术领域
本发明涉及医学制药领域，具体涉及RHPS4在制备抑制人类病原菌药物中的应用及其药物。
背景技术
病原微生物严重危害着人类健康。金黄色葡萄球菌 (Staphylococcus aureus)和铜绿假单胞菌(Pseudomonas aeruginosa)是常见的人兽共患病病原菌。其中金黄色葡萄球菌在空气、水以及人和动物的排泄物中广泛存在。研究发现大概有20％- 30％的人携带携带有金黄色葡萄球菌，而该菌分泌的脱皮毒素、溶血素和肠毒素等外毒素可引发人和动物发生多种疾病。人类感染金黄色葡萄球菌后容易导致食物中毒，并伴随着会恶心、呕吐、晕眩、甚至休克的症状。而铜绿假单胞菌常见于水、土壤、食品以及人的皮肤、呼吸道和肠道等潮湿的环境中，且对消毒剂的灭杀、紫外线的照射等理化处理具有很强的抵抗力。铜绿假单胞菌对抵抗力较弱的人群存在较大的健康风险。会导致胃肠黏膜有损伤的病人、婴幼儿产生腹泻，并引发泌尿系感染、败血症和脑膜炎等继发性疾病。因此，寻找开发新型的能够抑制病原微生物生长的活性化合物并研究其作用机理具有重要的意义。
发明内容
针对上述现有技术中存在的技术问题，本发明的目的是提供 RHPS4在制备抑制人类病原菌药物中的应用及其药物。
为了解决以上技术问题，本发明的技术方案为：
一方面，本发明提供了RHPS4在制备抑制人类病原菌药物中的应用，所述RHPS4的全称为3,11-二氟-6,8,13-三甲基-8H-喹啉并 [4,3,2-kl]吖啶鎓硫酸甲酯盐。
进一步地，所述人类病原菌包括金黄色葡萄球菌和铜绿假单胞菌。
另一方面，本发明还提供了一种抑制人类病原菌的药物，所述药物的活性成分包括3,11-二氟-6,8,13-三甲基-8H-喹啉并[4,3,2- kl]吖啶鎓硫酸甲酯盐。
进一步地，所述药物还包括药学上可接受的辅料。
与现有技术相比，本发明具有以下有益效果：
其一、通过抗菌活性试验表明，3,11-二氟-6,8,13-三甲基-8H- 喹啉并[4,3,2-kl]吖啶鎓硫酸甲酯盐能够有效抑制金黄色葡萄球菌的生长，并且，在400μg/mL的浓度下，3,11-二氟-6,8,13-三甲基 -8H-喹啉并[4,3,2-kl]吖啶鎓硫酸甲酯盐对金黄色葡萄球菌的抑制率达到88.65％，效果显著；因此，可以将3,11-二氟-6,8,13-三甲基-8H-喹啉并[4,3,2-kl]吖啶鎓硫酸甲酯盐应用于制备抑制金黄色葡萄球菌的药物，为金黄色葡萄球菌引起的疾病提供新的治疗药物。
其二、通过抗菌活性试验表明，3,11-二氟-6,8,13-三甲基-8H- 喹啉并[4,3,2-kl]吖啶鎓硫酸甲酯盐能够有效抑制铜绿假单胞菌的生长，并且，在400μg/mL的浓度下，3,11-二氟-6,8,13-三甲基- 8H-喹啉并[4,3,2-kl]吖啶鎓硫酸甲酯盐对铜绿假单胞菌的抑制率达到40.11％，效果显著；因此，可以将3,11-二氟-6,8,13-三甲基- 8H-喹啉并[4,3,2-kl]吖啶鎓硫酸甲酯盐应用于制备抑制铜绿假单胞菌的药物，为铜绿假单胞菌引起的疾病提供新的治疗药物。
附图说明
图1是不同浓度的3,11-二氟-6,8,13-三甲基-8H-喹啉并
[4,3,2-kl]吖啶鎓硫酸甲酯盐对金黄色葡萄球菌的抑制率；
图2不同浓度的3,11-二氟-6,8,13-三甲基-8H-喹啉并[4,3,2- kl]吖啶鎓硫酸甲酯盐对铜绿假单胞菌的抑制率。
具体实施方式
以下结合附图对本发明作进一步详细说明。
需要说明的是，除非本文另有定义，连同本发明使用的科学和技术术语应具有本领域普通技术人员通常理解的含义。术语的含义和范围应当清晰，然而，在任何潜在不明确性的情况下，本文提供的定义优先于任何字典或外来定义。在本申请中，除非另有说明，术语“包括”及其他形式的使用是非限制性的。
实施例：
一方面，本发明提供了RHPS4在制备抑制人类病原菌药物中的应用，所述RHPS4的全称为3,11-二氟-6,8,13-三甲基-8H-喹啉并 [4,3,2-kl]吖啶鎓硫酸甲酯盐。
进一步地，所述人类病原菌包括金黄色葡萄球菌和铜绿假单胞菌。
具体地，所述3,11-二氟-6,8,13-三甲基-8H-喹啉并[4,3,2-kl]吖啶鎓硫酸甲酯盐的结构式如式(Ⅰ)所示：
另一方面，本发明还提供了一种抑制人类病原菌的药物，所述药物的活性成分包括上述3,11-二氟-6,8,13-三甲基-8H-喹啉并
[4,3,2-kl]吖啶鎓硫酸甲酯盐。
进一步地，所述药物还包括药学上可接受的辅料。
药学上可接受的辅料是指生产药品和调配处方时，使用的赋形剂和附加剂，是指除活性成分外，在安全性方面已进行了合理的评估，并且包含在药物制剂中的物质。同一药用辅料可用于不同给药途径的药物制剂，且有不同的作用和用途。在本发明提供的药物中添加的药学上可接受的辅料，能够起到赋型、充当载体或提高稳定性的作用，此外，还具有增溶、助溶或缓控释等重要功能。
典型但非限制性的药学上可接受的辅料包括：溶剂、抛射剂、增溶剂、助溶剂、乳化剂、着色剂、黏合剂、崩解剂、填充剂、润滑剂、湿润剂、渗透压调节剂、稳定剂、助流剂、矫味剂、防腐剂、助悬剂、包衣材料、芳香剂、抗黏着剂、抗氧剂、螯合剂、渗透促进剂、pH调节剂、缓冲剂、增塑剂、表面活性剂、发泡剂、消泡剂、增稠剂、包合剂、保湿剂、吸收剂、稀释剂、絮凝剂与反絮凝剂、助滤剂或释放阻滞剂中的一种或多种。
需要注意的是，基于本发明提供的3,11-二氟-6,8,13-三甲基- 8H-喹啉并[4,3,2-kl]吖啶鎓硫酸甲酯盐具有抑制金黄色葡萄球菌和铜绿假单胞菌的作用，因此，包含3,11-二氟-6,8,13-三甲基-8H- 喹啉并[4,3,2-kl]吖啶鎓硫酸甲酯盐的药物也可以在金黄色葡萄球菌和铜绿假单胞菌引起的疾病治疗中起到治疗效果。
本发明对抑制人类病原菌药物的活性成分不做具体限定，在包含3,11-二氟-6,8,13-三甲基-8H-喹啉并[4,3,2-kl]吖啶鎓硫酸甲酯盐的基础上，根据实际应用，还可以包含在功能上能够起到协同作用或联合用药的其他活性成分。
试验一：
3,11-二氟-6,8,13-三甲基-8H-喹啉并[4,3,2-kl]吖啶鎓硫酸甲酯盐对金黄色葡萄球菌生长的影响。
金黄色葡萄球菌培养于37℃、180r/min，LB培养基中；
LB液体培养基制备：10g蛋白胨，5g酵母提取物，10 g NaCl，溶于1L去离子水中，121℃灭菌15min；
铺板：取发酵完全的细菌培养液，以每孔100μL加入到96孔板中；
加药：通过无菌水将3,11-二氟-6,8,13-三甲基-8H-喹啉并
[4,3,2-kl]吖啶鎓硫酸甲酯盐稀释成
4000、2000、1000、500、125、62.5和0μg/mL浓度的母液，备用。分别取20μL不同浓度的3,11-二氟-6,8,13-三甲基-8H-喹啉并 [4,3,2-kl]吖啶鎓硫酸甲酯盐母液加入到100μL菌液中，再加入 80μL的的培养基。继续在37℃培养24h；
检测：将96孔板中的菌液置于酶联免疫检测仪进行检测，检测波长为至于OD600，结果如图1所示。
从图1数据可以看出，3,11-二氟-6,8,13-三甲基-8H-喹啉并
[4,3,2-kl]吖啶鎓硫酸甲酯盐能够有效抑制金黄色葡萄球菌的生长，并且，在400μg/mL的浓度下，3,11-二氟-6,8,13-三甲基-8H-喹啉并[4,3,2-kl]吖啶鎓硫酸甲酯盐对金黄色葡萄球菌的抑制率达到 88.65％，效果显著。
试验二：
3,11-二氟-6,8,13-三甲基-8H-喹啉并[4,3,2-kl]吖啶鎓硫酸甲酯盐对铜绿假单胞菌生长的影响。
铜绿假单胞菌养于37℃、180r/min，LB培养基中；
铺板：取发酵完全的细菌培养液，以每孔100μL加入到96孔板中；
加药：通过无菌水将3,11-二氟-6,8,13-三甲基-8H-喹啉并
[4,3,2-kl]吖啶鎓硫酸甲酯盐稀释成
4000、2000、1000、500、125、62.5和0μg/mL浓度的母液，备用。分别取20μL不同浓度的3,11-二氟-6,8,13-三甲基-8H-喹啉并 [4,3,2-kl]吖啶鎓硫酸甲酯盐母液加入到100μL菌液中，再加入 80μL的的培养基。继续在37℃培养24h；
检测：将96孔板中的菌液置于酶联免疫检测仪进行检测，检测波长为至于OD600，结果如图2所示。
从图2数据可以看出，3,11-二氟-6,8,13-三甲基-8H-喹啉并
[4,3,2-kl]吖啶鎓硫酸甲酯盐能够有效抑制铜绿假单胞菌的生长，并且，在400μg/mL的浓度下，3,11-二氟-6,8,13-三甲基-8H-喹啉并[4,3,2-kl]吖啶鎓硫酸甲酯盐对铜绿假单胞菌的抑制率达到40.11％，效果显著。
上述实施例仅仅是本发明的部分实施例而已，并非对本发明作任何形式上的限制；任何熟悉本领域的技术人员，在不脱离本发明技术方案范围情况下，都可利用上述揭示的方法和技术内容对本发明技术方案做出许多可能的变动和修饰，或修改为等同变化的等效实施例。因此，凡是未脱离本发明技术方案的内容，依据本发明的技术实质对以上实施例所做的任何简单修改、等同替换、等效变化及修饰，均仍属于本发明技术方案保护的范围内。
Claims (4)
1.RHPS4在制备抑制人类病原菌药物中的应用，所述RHPS4的全称为3,11-二氟-6,8,13-三甲基-8H-喹啉并[4,3,2-kl]吖啶鎓硫酸甲酯盐。
2.根据权利要求1所述的应用，其特征在于：所述人类病原菌包括金黄色葡萄球菌和铜绿假单胞菌。
3.一种抑制人类病原菌的药物，其特征在于：所述药物的活性成分包括3,11-二氟-6,8,13-三甲基-8H-喹啉并[4,3,2-kl]吖啶鎓硫酸甲酯盐。
4.根据权利要求3所述的药物，其特征在于：所述药物还包括药学上可接受的辅料。
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