CN111450047A - 一种mers病毒免疫凝胶制剂的合成方法 - Google Patents
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Abstract
本发明公布一种MERS病毒免疫凝胶制剂的合成方法。主要步骤包括:1)PLGA‑PEG‑PLGA凝胶溶液的制备;2)混合法制备CpG‑S蛋白@ICG病毒免疫凝胶。CpG可全身性激活机体免疫功能,形成肌体对MERS病毒的免疫反应,并形成免疫记忆。吲哚菁绿(ICG)的荧光效应使疫苗接种的过程可视化,其产生的光热效应也可清除剩余的病毒。PLGA‑PEG‑PLGA无毒,生物相容性好,在常温下呈液态,35度左右相变为凝胶,可以很好地用于体内注射,延长药物在体内的滞留,从而提高效果。MERS病毒免疫凝胶可很好地预防MERS病毒的感染。
Description
技术领域
本发明涉及凝胶制剂的合成技术领域,具体涉及一种通过PLGA-PEG-PLGA包裹MERS病毒S蛋白、吲哚菁绿(ICG)和CpG的策略,合成病毒免疫凝胶制剂的方法。
背景技术
目前,冠状病毒是世界上对人类威胁最大的流行性疾病之一。免疫治疗通过激活人体免疫系统,依靠自身免疫机能杀灭病毒,从而达到预防病毒感染的作用。鉴于CpG可以作为异物在体内可以激发全身免疫系统产生细胞因子风暴(如干扰素和各种白细胞介素等),并使在抗病毒过程中具有重要作用的树突状细胞(DC细胞,提呈病毒抗原),巨噬细胞(RAW细胞,吞噬病毒)和自然杀伤细胞(NK细胞,杀伤病毒)等被大量激活,随后大幅提高T细胞的增值效率。这种基于CpG的免疫凝胶通过激活患者自身免疫系统,利用病毒的特征S蛋白诱导机体的特异性细胞免疫和体液免疫反应,增强机体的抗癌病毒能力,阻止病毒的感染,以达到清除或控制病毒扩散的目的。
ICG化学名为吲哚菁绿,是一种感光染料,是美国食品药品监督管理局(FDA)惟一批准的体内应用染料。它注入血液后会迅速与清蛋白及α1-脂蛋白结合(98%),随血液经过肝脏时,90%以上被肝细胞摄取,再以原形由胆道排泄,不参与体内化学反应,无肠肝循环,无淋巴逆流,不从肾脏等肝外脏器排泄,无辐射,无毒副作用。
PLGA-PEG-PLGA是一种三嵌段聚合物。其中PLGA由两种单体——乳酸和羟基乙酸随机聚合而成,是一种可降解的功能高分子有机化合物,其降解产物是乳酸和羟基乙酸,同时也是人代谢途径的副产物,所当它应用在医药和生物材料中时不会有毒副作用,具有良好的生物相容性、无毒、良好的成囊和成膜的性能。PEG具有良好的水溶性,生物相容性好,并赋予了聚合物温敏相变的性质。
发明内容
本发明为克服现有技术的不足,提供一种通过PLGA-PEG-PLGA包裹MERS病毒S蛋白、吲哚菁绿(ICG)和CpG的策略,合成病毒免疫凝胶制剂的方法。利用病毒S蛋白诱导机体的特异性细胞免疫和体液免疫反应,增强机体的抗病毒能力,阻止病毒的感染,以达到清除或控制病毒扩散的目的。
本发明的技术方案是一种病毒免疫凝胶制剂的合成方法,通过PLGA-PEG-PLGA包裹MERS病毒S蛋白,吲哚菁绿(ICG)和CpG的策略,具体步骤如下:
1)称取PLGA-PEG-PLGA材料,加入水中溶解,得到浓度为0.2-0.5mg/ml的PLGA溶液;
2)称取ICG材料,加入水中溶解,得到浓度为5-10mg/ml的ICG溶液;
3)各取适量混合成病毒免疫凝胶。
所述步骤3)具体如下:
(1)在室温下将盛有1ml的PLGA-PEG-PLGA溶液的单口瓶置于旋转搅拌器上,搅拌速度设定为500r/min;
(2)边搅拌边逐滴加入8uL的ICG水溶液和20uL病毒S蛋白溶液和20uLCpG溶液,继续搅拌直至完全混匀,最终得到CpG-S蛋白@ICG病毒免疫凝胶。
本发明的优势在于:
1)CpG可以激活细胞免疫,增强机体的抗病毒能力,阻止病毒的感染,以达到清除或控制病毒扩散的目的。
2)吲哚菁绿(ICG)的荧光效应使疫苗接种的过程可视化,其产生的光热效应也可清除剩余的病毒蛋白。
3)PLGA-PEG-PLGA无毒,生物相容性好,在常温下呈液态,35度左右相变为凝胶,可以很好地用于体内注射,延长药物在体内的滞留,从而提高效果。
附图说明
图1:免疫凝胶活化淋巴T细胞流式图。
具体实施方式
以下结合附图和具体实施例来对本发明作进一步的说明。
实施例1:
1)准确称取0.25mg的PLGA-PEG-PLGA材料,加入1mL水溶解,得到浓度为0.25mg/ml的PLGA-PEG-PLGA水溶液。
2)准确称取5mg的ICG材料,加入1mL水溶解,得到浓度为5mg/ml的ICG水溶液。
3)混合法合成CpG-S蛋白@ICG病毒免疫凝胶的方法如下:
(1)在室温下将盛有1ml的PLGA-PEG-PLGA溶液的单口瓶置于旋转搅拌器上,搅拌速度设定为500r/min;
(2)边搅拌边逐滴加入8uL的ICG水溶液和20uL病毒S蛋白溶液和20uLCpG溶液,继续搅拌直至完全混匀,最终得到CpG-S蛋白@ICG病毒免疫凝胶。
实施例2:
1)准确称取0.2mg的PLGA材料,加入1mL水溶解,得到浓度为0.2mg/ml的PLGA有机溶液。
2)准确称取8mg的ICG材料,加入1mL水溶解,得到浓度为8mg/ml的ICG水溶液。
3)混合法合成CpG-S蛋白@ICG病毒免疫凝胶的方法如下:
(1)在室温下将盛有1ml的PLGA-PEG-PLGA溶液的单口瓶置于旋转搅拌器上,搅拌速度设定为500r/min;
(2)边搅拌边逐滴加入6uL的ICG水溶液和20uL病毒S蛋白溶液和20uLCpG溶液,继续搅拌直至完全混匀,最终得到CpG-S蛋白@ICG病毒免疫凝胶。
实施例3:
1)准确称取0.4mg的PLGA材料,加入1mL水溶解,得到浓度为0.4mg/ml的PLGA有机溶液。
2)准确称取6mg的ICG材料,加入1mL水溶解,得到浓度为6mg/ml的ICG水溶液。
3)混合法合成CpG-S蛋白@ICG病毒免疫凝胶的方法如下:
(1)在室温下将盛有1ml的PLGA-PEG-PLGA溶液的单口瓶置于旋转搅拌器上,搅拌速度设定为500r/min;
(2)边搅拌边逐滴加入10uL的ICG水溶液和20uL病毒S蛋白溶液和20uLCpG溶液,继续搅拌直至完全混匀,最终得到CpG-S蛋白@ICG病毒免疫凝胶。
Claims (2)
1.一种MERS病毒免疫凝胶制剂的合成方法,其特征是,通过PLGA-PEG-PLGA包裹MERS病毒S蛋白、吲哚菁绿(ICG)和免疫激活剂CpG的策略,具体步骤如下:
1)称取PLGA-PEG-PLGA材料,加入水中溶解,得到浓度为0.2-0.25mg/ml的PLGA-PEG-PLGA溶液;
2)称取ICG材料,加入水中溶解,得到浓度为5-10mg/ml的ICG溶液;
3)取6-10uL的ICG水溶液和20uL病毒S蛋白溶液和20uLCpG溶液加入1mlPLGA-PEG-PLGA水溶液中混合成病毒免疫凝胶。
2.根据权利要求1所述的MERS病毒免疫凝胶制剂的合成方法,其特征是,所述步骤3)具体如下:
(1)在室温下将盛有1ml的PLGA-PEG-PLGA溶液的单口瓶置于旋转搅拌器上,搅拌速度设定为500r/min;
(2)边搅拌边逐滴加入8uL的ICG水溶液和20uL MERS病毒S蛋白溶液和20uL CpG溶液,继续搅拌直至完全混匀,最终得到CpG-S蛋白@ICG病毒免疫凝胶。
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CN105555306A (zh) * | 2013-09-19 | 2016-05-04 | 诺瓦瓦克斯股份有限公司 | 免疫原性中东呼吸综合征冠状病毒(MERS-CoV)组合物和方法 |
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