CN115697382A - 具有抗病毒作用的口服使用的乳铁蛋白 - Google Patents
具有抗病毒作用的口服使用的乳铁蛋白 Download PDFInfo
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- CN115697382A CN115697382A CN202080098096.3A CN202080098096A CN115697382A CN 115697382 A CN115697382 A CN 115697382A CN 202080098096 A CN202080098096 A CN 202080098096A CN 115697382 A CN115697382 A CN 115697382A
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Abstract
本发明涉及一种包含乳铁蛋白的组合物,其作为抗病毒剂口服使用,优选用于治疗呼吸系统的病毒感染以及与病毒感染相关或由其导致的症状或病症,所述病毒感染优选SARS冠状病毒感染(例如COVID‑19)。
Description
本发明涉及一种包含乳铁蛋白的组合物,所述组合物用于作为抗病毒剂口服使用,优选用于治疗呼吸系统的病毒感染以及源自所述病毒感染或与其有关的症状或病症,所述病毒感染优选为SARS-冠状病毒的病毒感染(例如COVID-19)。
顾名思义,呼吸道病毒感染是由病毒引起的传染病,所述病毒影响上呼吸道系统和/或下呼吸道系统的器官(鼻、咽、喉、气管、支气管和肺)。
优选地,本发明涉及由严重急性呼吸综合征冠状病毒物种(缩写为SARS-CoV)的至少一种病毒引起的病毒感染。SARS-CoV物种的所述病毒是属于乙型冠状病毒属(genusBetacoronavirus)的正链RNA病毒(巴尔的摩分类法的第IV组)。
严重急性呼吸综合征冠状病毒物种的病毒称为SARS-CoV毒株。
在2019年末,被称为SARS-CoV-2毒株或2019-nCoV的严重急性呼吸综合征冠状病毒物种的另一病毒引起新SARS流行病,更通常称为COVID-19(冠状病毒疾病19,也称为SARS-CoV-2急性呼吸疾病-或冠状病毒疾病2019,也称为冠状病毒综合征2019)。
在深入研究和开发活动之后,申请人通过提供用于口服使用的组合物,克服并解决了治疗病毒感染的问题,优选是呼吸道(上呼吸道和下呼吸道)的病毒感染,特别是由严重急性呼吸综合征冠状病毒物种的至少一种病毒引起的呼吸道病毒感染(例如SARS-CoV、SARS-CoV-2/2019-nCoV毒株-其疾病被称为COVID-19-或SARS-CoV样),所述组合物包含乳铁蛋白或其衍生物,用于治疗所述病毒感染或与其相关的症状或病症的方法。
乳铁蛋白,也称为乳运铁蛋白,是多功能球状蛋白质。乳铁蛋白属于转铁蛋白家族,并且其具有约80KDa的分子质量,具有两个铁离子(Fe3+)结合位点,类似于转铁蛋白本身。乳铁蛋白从未被铁饱和,并且其铁含量是变化的。乳铁蛋白具有抗微生物活性、杀细菌、杀真菌和抵抗各种病毒。假设乳铁蛋白的抗微生物活性与其对Fe3+的亲和力相关,因此与其在自由状态下与铁依赖性微生物竞争的能力高相关,并且与对革兰氏阴性菌外部膜的直接作用相关。乳铁蛋白与在粘膜分泌物中铁离子的组合调节细菌和病毒对细胞膜的活性和聚集性。这是由于一些细菌和病毒需要铁以便执行细胞复制的事实,而乳铁蛋白则相反地将其从周围环境中除去,从而防止所述细菌和病毒增殖。
乳铁蛋白对DNA和RNA病毒(包括轮状病毒、呼吸道合胞病毒、疱疹病毒和HIV)表现出抗病毒活性。乳铁蛋白的抗病毒作用在于感染的早期阶段。乳铁蛋白通过阻断细胞受体或直接结合到病毒颗粒上而阻止病毒进入宿主细胞。具体地,乳铁蛋白的抗病毒作用主要在于其与质膜的糖胺聚糖结合的能力。此外,在文献中已知通过改善NK细胞活性和通过刺激嗜中性粒细胞聚集和粘附,乳铁蛋白参与宿主对严重急性呼吸综合征冠状病毒(SARS-CoV)的急性侵入的免疫响应。此外,考虑到HSPG是涉及SARS-CoV细胞进入的细胞表面的必要分子,已经假设乳铁蛋白可以通过结合到HSPG(HSPG,硫酸乙酰肝素蛋白聚糖,广泛分布)和通过阻断SARS-CoV和宿主细胞之间的初步相互作用来在对抗SARS-CoV感染的宿主防御中发挥保护作用。
在本发明的上下文中,表述“乳铁蛋白衍生物”用于指示源自乳铁蛋白的任何多功能肽或球状蛋白质,其显示类似的抗病毒作用,例如缺铁乳铁蛋白(apolactoferrin)或乳铁素(lactoferricin)。乳铁素是具有已知抗菌活性的乳铁蛋白衍生物,缺铁乳铁蛋白是其中N-末端叶(或缺铁乳铁蛋白)呈开放构象的乳铁蛋白。
基于乳铁蛋白或其衍生物的本发明的组合物,配制用于口服使用,优选以固体形式,可有效作为抗病毒剂,特别是有效用于治疗呼吸道病毒感染和与其相关的症状或病症,特别是由严重急性呼吸综合征冠状病毒物种的至少一种病毒(例如SARS-CoV、SARS-CoV-2或2019-nCoV毒株-导致称为COVID-19-或SARS-CoV样的疾病)引起的感染。
基于乳铁蛋白或其衍生物的本发明的组合物,可以通过添加特定的赋形剂和添加剂而配制为溶液或乳液或适合于雾化的分散体,并且施用(使用喷雾装置)至鼻和喉以用于吸入、口或鼻腔使用。所述可喷雾组合物有效作为抗病毒剂,特别是有效用于治疗呼吸道病毒感染和与其相关的症状或病症,特别是由严重急性呼吸综合征冠状病毒物种的至少一种病毒(例如SARS-CoV、SARS-CoV-2或2019-nCoV毒株-导致称为COVID-19-或SARS-CoV样的疾病)引起的感染。
基于乳铁蛋白或其衍生物的本发明的组合物没有相关副作用,并且它们可以施用给有需要的所有类别的受试者,包括老年人、妊娠及哺乳妇女、儿科受试者(0-12岁)、患有呼吸或心血管并发症或糖尿病或可能在病毒感染的情况下造成风险或危险的其他并发症的受试者。
此外,基于乳铁蛋白的本发明的组合物易于制备且有成本效益。
由于在说明书中报道并在所附权利要求中要求保护的技术特性,根据以下详细描述中清楚的这些和其它目的可通过本发明的组合物和混合物获得。
附图说明
图1A-D表示乳铁蛋白(L)对细胞因子/趋化因子和具有抗病毒作用或涉及由Caco-2肠上皮细胞产生的抗病毒响应的分子的组的作用。
图2A和2B示意性地表示相对于用SARS-CoV-2病毒处理,在用乳铁蛋白(L)进行预处理或共处理之后,对Caco-2肠上皮细胞中的抗病毒响应进行评估的体外研究的图。
图3A-E表示相对于用SARS-CoV-2病毒处理,在用乳铁蛋白(L)进行预处理之后,乳铁蛋白(L)对细胞因子/趋化因子和具有抗病毒作用或涉及由Caco-2肠上皮细胞产生的抗病毒响应的分子的组的作用。
图4A-D表示在用乳铁蛋白(L)和SARS-CoV-2病毒共处理后,乳铁蛋白(L)对细胞因子/趋化因子和具有抗病毒作用或涉及由Caco-2肠上皮细胞产生的抗病毒响应的分子的组的作用。
具体实施方式
本发明的目的是一种用于口服使用的组合物(简言之,本发明的组合物),其用作抗病毒剂,优选用于预防性和/或治疗性治疗有需要的受试者中呼吸系统(上呼吸道和/或下呼吸道)的病毒感染以及源自所述病毒感染或与所述病毒感染有关的症状或病症的方法,其中所述组合物包括:
(i)混合物M(简言之,本发明的混合物M),其包含乳铁蛋白(简言之LF)或其可接受的药用级衍生物或由其组成:和任选的,
(ii)至少一种可接受的药用级添加剂和/或赋形剂。
优选地,使用本发明的组合物治疗的病毒感染是由以下病毒引起的感染:冠状病毒科,冠状病毒亚科,乙型冠状病毒属,严重急性呼吸综合征冠状病毒种(简言之,SARS-CoV或SARS-冠状病毒);其选自以下株:(I)严重急性呼吸综合征冠状病毒(SARS-CoV或SARS),(II)严重急性呼吸综合征冠状病毒-2(SARS-CoV-2或2019-nCoV-导致称为COVID-19的疾病),和(III)严重急性呼吸综合征冠状病毒样病毒(SARS-CoV-样或SL-CoV);优选地,SARS-CoV-2或2019-nCoV,其导致称为COVID-19的疾病。
简言之,在本发明的上下文中,这些病毒(例如(I)、(II)和(III))被称为“SARS-冠状病毒物种的病毒”或简称为“SARS-冠状病毒”。
由呼吸道(上呼吸道和/或下呼吸道)的病毒感染、优选如上所述的冠状病毒感染(例如,SARS-CoV、SARS-CoV-2或2019-nCoV、SARS-CoV-样)导致或与其有关的症状或病症可以是:严重急性呼吸综合征(SARS)、呼吸并发症、哮喘、慢性阻塞性肺病(COPD)、支气管炎(bronchitis)、肺气肿、囊性纤维化、咳嗽、百日咳、肺炎、胸膜炎(pleurisy)、细支气管炎(bronchiolitis)、感冒、鼻窦炎、鼻炎、气管炎、咽炎、喉炎、急性喉气管支气管炎(acutelaryngotracheobronchitis)、会厌炎、支气管扩张、呼吸困难、气喘(dyspnoea、呼吸急促(breathlessness)、呼吸短促)、发烧、疲劳、肌肉痛(muscle aches)和/或疼痛(musclepain)、鼻塞、流鼻涕、咽喉痛(sore throat)、胃肠症状例如恶心和腹泻、肾衰竭、食欲不振和/或总体不适感(general feeling unwell)。
相对于组合物或混合物M的总重量,以%重量计,乳铁蛋白可以以10%至90%存在于本发明的组合物中或本发明的混合物M中(例如,15%、20%、25%、30%、35%、40%、45%、50%、55%、60%、65%、70%、75%、80%或85%),优选20%至80%,更优选30%至70%或30%至50%。
根据本发明的任何一个实施方式的包含所述混合物M的本发明的组合物可以还包含所述至少一种药物或食品级添加剂和/或赋形剂,即,不具有适合于药物或食品用途的治疗活性的物质。在本发明的上下文中,对于药物或食品用途而言可接受的添加剂和/或赋形剂包括本领域技术人员已知的用于制备固体、半固体或液体形式的组合物的所有辅助物质,例如稀释剂、溶剂(包括水、甘油、乙醇)、增溶剂、酸化剂、增稠剂、甜味剂、增香剂、着色剂、润滑剂、表面活性剂、防腐剂、稳定剂、pH稳定缓冲剂以及它们的混合物。
用于本发明的口服使用的组合物可以固体形式或液体形式或半液体形式配制,所述固体形式选自:片剂、咀嚼片、口服可溶性片剂、颗粒剂、粉末剂、薄片剂、可溶性粉末剂或颗粒剂、口腔可溶性粉末剂或颗粒剂、胶囊剂;所述液体形式选自:溶液剂、悬浮剂、分散剂、乳液剂、能够以喷雾形式分配的液体、糖浆;所述半液体形式选自:软凝胶、凝胶;优选地,本发明的组合物是固体形式。
在根据本发明所述的任何一个实施方式的本发明的组合物的混合物M中,乳铁蛋白可以为脂质体形式,例如磷脂类脂质体形式。
乳铁蛋白的所述脂质体形式(或制剂)可以在施用(通过口服或喷雾制剂在鼻腔内)后降低乳铁蛋白的清除率,并因此增加其吸收程度。此外,由脂质体携带的物质受保护免遭酶(蛋白酶、核酸酶)或变性环境(pH)的作用。脂质体是由一个或多个脂双层形成的中空微球,其膜通常由胆固醇(或胆固醇酯)和磷脂如磷脂酰胆碱、二乙酰基磷酸酯和磷脂酰乙醇胺组成。脂质体的尺寸可以为20nm至25nm,至多至2.5μm。
在本发明的上下文中,用于口服使用的术语用于表示口服(或肠溶)施用和舌下(或经颊)施用。
本发明的用于口服使用的组合物(优选以固体形式),作为抗病毒剂是有效的,特别是在治疗由SARS冠状病毒(优选SARS-CoV或2019-nCoV,其导致称为COVID-19的疾病)引起的呼吸道感染是有效的,乳铁蛋白的每日剂量为5mg至1000mg,优选10mg至500mg,更优选20mg至400mg,例如50mg至350mg,50mg至300mg、50mg至250mg、50mg至200mg、100mg至200mg。
前述日剂量可以单次剂量(一剂)或重复剂量(例如两个、三个或四个日剂量)施用给受试者。
根据所述实施方式中的任一种的本发明的组合物可以用作另外的抗病毒治疗方法的佐剂。
除非另有说明,否则即使未指定,表述包含“x至y”的量的组分的组合物或混合物或其它表达也用于表示所述组分可以以所述范围中存在的所有量存在于所述组合物或混合物或其它表达中,包括所述范围的端值。
除非另有说明,否则“包含”一种或多种组分或物质的组合物或混合物的指示是指除了具体指出的一种或多种组分或物质之外,还可以存在其他组分或物质。
在本发明的上下文中,表达“治疗方法”用于表示对有需要的受试者的干预,包括施用治疗有效量(根据本领域技术人员)的物质的组合物或混合物,其目的是消除、减少/降低或预防疾病或病痛以及其症状或病症。
在本发明的上下文中,术语“受试者”用于表示人或动物受试者,优选哺乳动物(例如宠物,如狗、猫、马、羊或牛)。优选地,本发明的组合物用于人类受试者的治疗方法。
下面报道了本发明FRn的优选实施方式。
FR1.一种应用于病毒感染的治疗方法的组合物,其中所述组合物包含:
(i)乳铁蛋白,和任选的,
(ii)至少一种可接受的药用级添加剂和/或赋形剂;并且
其中所述组合物应用于通过口服途径使用。
FR2.根据FR1所述应用的组合物,其中所述组合物用于治疗呼吸系统的病毒感染和由所述病毒感染导致或与其相关的症状和/或病症的方法;优选地,所述病毒感染为上呼吸道和/或下呼吸道的病毒感染。
FR3.根据FR1或FR2所述应用的组合物,其中所述病毒感染由冠状病毒科,冠状病毒亚科,乙型冠状病毒属,严重急性呼吸综合征冠状病毒种的病毒引起,其选自下述株:严重急性呼吸综合征冠状病毒(SARS-CoV)、导致COVID-19疾病的严重急性呼吸综合征冠状病毒-2(SARS-CoV-2或2019-nCoV),和严重急性呼吸综合征冠状病毒样冠状病毒(SARS-CoV-样或SL-CoV);优选SARS-CoV-2。
FR4.根据FR2或FR3所述应用的组合物,其中由呼吸系统的所述病毒感染导致或与其相关的所述症状和/或病症选自:严重急性呼吸综合征(SARS)、呼吸并发症、哮喘、慢性阻塞性肺病(COPD)、支气管炎、肺气肿、囊性纤维化、咳嗽、百日咳、肺炎、胸膜炎、细支气管炎、感冒、鼻窦炎、鼻炎、气管炎、咽炎、喉炎、急性喉气管支气管炎)、会厌炎、支气管扩张、呼吸困难、气喘、呼吸急促、呼吸短促、发烧、疲劳、肌肉痛、肌肉疼痛、鼻塞、流鼻涕、咽喉痛、胃肠症状、恶心、腹泻、肾衰、食欲不振、总体不适感。
FR5.根据前述FRns中任一项所述应用的组合物,其中所述组合物为固体形式或液体形式或半液体形式,所述固体形式选自:片剂、咀嚼片、口服可溶性片剂、颗粒剂、粉末剂、薄片剂、可溶性粉末剂或颗粒剂、口腔可溶性粉末剂或颗粒剂、胶囊剂;所述液体形式选自:溶液剂、悬浮剂、分散剂、乳液剂、能够以喷雾形式分配的液体、糖浆;所述半液体形式选自:软凝胶、凝胶;优选为固体形式。
FR6.根据前述FRns中任一项所述应用的组合物,其中乳铁蛋白是脂质体形式;优选磷脂类脂质体形式。
实验部分
本申请人进行了体外研究,以评估乳铁蛋白刺激受试者的先天抗病毒免疫响应从而对抗SARS-CoV-2(COVID-19)病毒感染的能力。详细来说,评估以下内容:
(1)乳铁蛋白增强肠上皮细胞中抗病毒响应的能力;
(2)乳铁蛋白影响人肠道上皮细胞中SARS-CoV-2感染的能力。
材料(1)和(2)
-Caco-2细胞的汇合单层(来自结肠癌的永生化上皮细胞):从欧洲认证细胞培养物保藏中心(ECACC)获得Caco-2细胞,并且在含有5% CO2的加湿温育器中在37℃下在完全DMEM培养基(补充有10%(v/v)胎牛血清(FBS)、1%(v/v)丙酮酸钠和1%(v/v)青霉素和链霉素的达尔伯克氏改良伊格尔氏培养基(Dulbecco's Modified Eagle Medium))中在T 25瓶中生长,在达到约75%的汇合时分离,并在12个孔/板中以5x105个细胞/孔的浓度接种。每48小时更换培养基,直到细胞形成汇合单层。然后,去除培养基并更换为不含抗生素的新鲜培养基。
-乳铁蛋白(代码“L”)(100μg/mL)。
-SARS-CoV-2病毒(代码,“SARS”):其在Padua中从患者分离并且完全表征;病毒在VERO C1008细胞上繁殖,以获得工作储备液,将其贮存在-80℃。
1.在肠上皮细胞中乳铁蛋白对抗病毒响应的效果
1.1.方法
1)将Caco-2细胞的汇合单层仅与培养基(对照,代码“nt”:未处理)或与乳铁蛋白(代码“L”)一起温育2小时。
2)在4小时之后去除培养基,更换为含有抗生素的完全培养基,并将单层在37℃下再温育16小时。
3)在温育结束时除去培养基,用冷冻DMEM洗涤单层,收集细胞并立即裂解。从细胞中提取总RNA,将其转录成cDNA(iScriptTM Select cDNA合成试剂盒(Bio Rad)),并用于对以下mRNA转录子进行定量RT-PCR。
·IFN-β和IFN-α,具体用于抗病毒作用;
·IRF-3和IRF-7,与干扰素(抗病毒分子)连接的信号传导分子;
·TLR3和TLR7,先天性免疫的特异性受体,其“看到”病毒RNA并引发抗病毒响应;
·IL-10和TGF-β,抗炎标志物;
·IL6,促炎标志物
4)所有测试进行三次。使用持家基因Rn18S作为参考。使用ΔΔCt(倍数变化)方法分析数据。
1.2.结果
乳铁蛋白能够刺激先天免疫防御(TLR3和TLR7;图1A),施加良好的抗炎响应(对IL-10、TGF-β的显著数据;图1B),并且具有减少促炎标志物(IL6;图1C)的趋势。此外,乳铁蛋白对涉及抗病毒响应的若干信号途径(IFN-β、IFN-α、IRF-3和IRF-7;图1D)显示出显著的活性。
将编码α和β干扰素(IFN-α和IFN-β)的基因的表达定量为响应于病毒存在而从宿主细胞zhong释放的信号传导蛋白。人类肠粘膜产生这些分子以对抗病毒感染。
其它细胞因子就基因表达来定量:IL-10和TGF-β,其为抗炎标志物;刺激抗炎细胞因子表达是用于制衡病毒感染的有害作用的有价值的工具。
此外,TLR3和TRL7受体通过识别单链RNA和双链RNA而参与对病毒的反应;通常,TLR的活化导致干扰素释放。
2.乳铁蛋白对人肠上皮细胞中SARS-CoV-2感染的效果
2.1.方法
根据图2A和2B中报告的方案,相对于使用SARS-CoV-2病毒的处理,用乳铁蛋白(代码“L”)预处理或共处理Caco-2细胞的汇合单层;获得的结果与单独用培养基(对照,代码“nt”)处理的Caco-2细胞和单独用SARS-CoV-2病毒(代码“SARS-CoV-2”)处理的Caco-2细胞进行比较。
在温育结束时,对于每种类型的处理,除去培养基,从细胞中提取总RNA,将其转录成cDNA,并将其用于对以下mRNA转录子进行定量RT-PCR。
··IFN-α和IFN-β,具体用于抗病毒作用;
·TLR3和TLR7,其是先天免疫的特异性受体,其“看到”病毒RNA并引发抗病毒响应;
·MDA5和MAVS,在细胞中涉及抗病毒响应的基因的病毒受体;
·TGF-β,抗炎标志物;
·IL-1β和IL-8,促炎标志物;
·TSLP1,从肠上皮细胞释放的细胞因子,其对树突细胞和巨噬细胞的抗炎表型的调节具有重要作用。
所有测试和结果进行三次。使用持家基因Rn18S作为参考。使用ΔΔCt(倍数变化)方法分析数据。
预处理方案(图2A):每个孔仅用培养基温育(对照,代码“nt”)或用100μg/ml的乳铁蛋白处理。3小时后,除去培养基,更换为含有抗生素的新鲜培养基,并使单层感染SARS-CoV-2。
共处理方案:每个孔仅与培养基温育(对照,代码“nt”)或用100μg/ml乳铁蛋白处理。同时,使细胞感染SARS-CoV-2。在这些实验中,培养基在2小时后从所有孔中移出并更换为含有抗生素的新鲜培养基。
2.2.结果
该研究显示乳铁蛋白能够在感染SARS-CoV-2病毒的细胞中发挥抗病毒和抗炎作用,定义了乳铁蛋白适合于COVID-19的预防性和治疗性治疗。
在图3中报告的结果示出乳铁蛋白:
-在预处理时诱导干扰素IFN-α和IFN-β(图3A),
-在预处理时诱导TRL3(图3B),
-在共处理时诱导TRL3(图4A),以及
-在共处理时诱导Mavs和Mda5(图4B),其涉及病毒识别。
此外,观察了乳铁蛋白的抗炎作用:
-在预处理时降低IL-8的表达(图3C),并且在共处理时降低IL-1β的表达(图4C),
-在预处理时(图3D)和在共处理时(图4C)降低TSLP1的表达,以及
-在预处理时(图3E)和在共处理时(图4D)增加抗炎标志物TGF-β的表达。
通过乳铁蛋白,显著激活TGF-β的表达。
基于与干扰素诱导相关的反应级联,TLR受体由乳铁蛋白激活,所述乳铁蛋白对TLR3特别具有活性且对TLR7具有适度活性。
抗病毒免疫响应的起始阶段由MAVS和MDA5介导;已经发现乳铁蛋白能够触发MAVS,尽管不显著。
在预处理模型中,通过乳铁蛋白显著降低TSLP1表达,证明乳铁蛋白有助于降低病毒诱导的炎性病症。
TSLP1是从肠上皮细胞中释放的细胞因子,其对树突细胞和巨噬细胞的抗炎表型的调节具有重要效果。
结论(1)和(2)
所获得的结果表明,在预处理和共处理实验方案的两种情况下,乳铁蛋白都能够正向地调节抗病毒和抗炎响应,因此在抗病毒治疗中是有用的佐剂。
事实上,从文献可知,在COVID-19患者中已经观察到促炎细胞因子表达的增加,并且LDH、CRP、PCT血清水平和铁蛋白在具有非常严重的COVID-19的患者中相对于不严重的患者有显著增加。高水平的铁蛋白和IL-6被认为是致死率的预测因子,这表明死亡率可能归因于由病毒引起的过度炎症。
由于其抗炎和抗病毒性质,乳铁蛋白(或乳运铁蛋白)能够降低炎性病症。已显示乳铁蛋白、抗微生物作用糖蛋白和铁载体能够对感染/发炎细胞中的IL-6施加抗炎作用,因此有利于铁蛋白的下调、铁蛋白是铁稳态和炎性过程中的关键因素。
Claims (6)
1.一种应用于病毒感染的治疗方法的组合物,其中,所述组合物包含:
(i)乳铁蛋白,和任选的
(ii)至少一种可接受的药用级添加剂和/或赋形剂;并且
其中所述组合物应用于通过口服途径使用。
2.根据权利要求1所述应用的组合物,其中,所述组合物用于治疗呼吸系统的病毒感染和由所述病毒感染导致或与其相关的症状和/或病症的方法;优选地,所述病毒感染为上呼吸道和/或下呼吸道的病毒感染。
3.根据权利要求1或2所述应用的组合物,其中,所述病毒感染由冠状病毒科,冠状病毒亚科,乙型冠状病毒属,严重急性呼吸综合征冠状病毒种的病毒引起,其选自下述株:严重急性呼吸综合征冠状病毒(SARS-CoV)、导致COVID-19疾病的严重急性呼吸综合征冠状病毒-2(SARS-CoV-2或2019-nCoV),和严重急性呼吸综合征冠状病毒样冠状病毒(SARS-CoV-样或SL-CoV);优选SARS-CoV-2。
4.根据权利要求2或3所述应用的组合物,其中,呼吸系统的所述病毒感染导致或与其相关的所述症状和/或病症选自:严重急性呼吸综合征(SARS)、呼吸并发症、哮喘、慢性阻塞性肺病(COPD)、支气管炎、肺气肿、囊性纤维化、咳嗽、百日咳、肺炎、胸膜炎、细支气管炎、感冒、鼻窦炎、鼻炎、气管炎、咽炎、喉炎、急性喉气管支气管炎、会厌炎、支气管扩张、呼吸困难、气喘、呼吸急促、呼吸短促、发烧、疲劳、肌肉痛、肌肉疼痛、鼻塞、流鼻涕、咽喉痛、胃肠症状、恶心、腹泻、肾衰、食欲不振、总体不适感。
5.根据前述权利要求中任一项所述应用的组合物,其中,所述组合物为固体形式或液体形式或半液体形式,优选为固体形式,所述固体形式选自:片剂、咀嚼片、口腔可溶性片剂、颗粒剂、粉末剂、薄片剂、可溶性粉末剂或颗粒剂、口腔可溶性粉末剂或颗粒剂、胶囊剂;所述液体形式选自:溶液剂、悬浮剂、分散剂、乳液剂、能够以喷雾形式分配的液体、糖浆;所述半液体形式选自:软凝胶、凝胶。
6.根据前述权利要求中任一项所述应用的组合物,其中,乳铁蛋白是脂质体形式;优选磷脂类脂质体形式。
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US20240091153A1 (en) * | 2021-02-01 | 2024-03-21 | Dermopartners, S.L. | Composition for use as an antiviral in the form of nasal drops and in nebulisers |
JPWO2022172523A1 (zh) * | 2021-02-09 | 2022-08-18 | ||
WO2024018374A1 (en) | 2022-07-20 | 2024-01-25 | Frimline Private Limited | A pharmaceutical composition providing mucolytic effect |
WO2024149375A1 (en) * | 2023-01-13 | 2024-07-18 | The Chinese University Of Hong Kong | Synbiotic compositions for improving immunity and for treating atopic dermatitis |
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JPH06316529A (ja) * | 1991-12-03 | 1994-11-15 | Imuno Japan:Kk | レンチウイルス感染に随伴する日和見感染症の治療予 防用医薬組成物 |
JPH1171301A (ja) * | 1997-08-29 | 1999-03-16 | Morinaga Milk Ind Co Ltd | 抗動物感染性ウイルス剤及び飼料 |
AU4486501A (en) * | 2000-03-27 | 2001-10-08 | Pharming Intellectual Property Bv | High dosage parenteral administration of lactoferrin |
JP2004083487A (ja) * | 2002-08-27 | 2004-03-18 | Morinaga Milk Ind Co Ltd | 抗ウイルス組成物及びウイルス感染症予防・治療用組成物 |
WO2006047744A2 (en) * | 2004-10-26 | 2006-05-04 | Agennix Incorporated | Compositions of lactoferrin related peptides and uses thereof |
CN101939411A (zh) * | 2008-02-06 | 2011-01-05 | 宝洁公司 | 用于提高呼吸病症免疫应答的组合物、方法和试剂盒 |
IT1392672B1 (it) * | 2009-01-12 | 2012-03-16 | Wyeth Consumer Healthcare S P A | Composizioni comprendenti componenti probiotici e prebiotici e sali minerali, con lactoferrina |
KR101235561B1 (ko) * | 2010-12-09 | 2013-03-21 | 주식회사 제일바이오 | 항바이러스 및 항균 활성을 갖는 락토바실러스 플란타룸 clp-1 균주 및 이를 포함하는 생균제 |
CN117942405A (zh) * | 2016-02-25 | 2024-04-30 | 应用生物实验室公司 | 保护空气传播的病原体和刺激物的组合物和方法 |
WO2018191073A1 (en) * | 2017-04-12 | 2018-10-18 | The Uab Research Foundation | Inhaled respiratory probiotics for lung diseases of infancy, childhood and adulthood |
WO2019089878A1 (en) * | 2017-11-02 | 2019-05-09 | Colorado Seminary, Owner and Operator of University of Denver | Methods of treating microbial infection and inflammation |
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CN116509821A (zh) * | 2023-03-07 | 2023-08-01 | 广州见华医学科技有限公司 | 一种乳铁蛋白贴剂在制备用于冠状病毒引起感染性疾病治疗药物中的用途 |
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CN115279397A (zh) | 2022-11-01 |
JP2023516461A (ja) | 2023-04-19 |
MX2022010874A (es) | 2022-10-07 |
EP4117711A2 (en) | 2023-01-18 |
WO2020250209A2 (en) | 2020-12-17 |
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