CN115701990A - 用于治疗冠状病毒感染、反转录病毒感染和丙型肝炎的药品/药物 - Google Patents
用于治疗冠状病毒感染、反转录病毒感染和丙型肝炎的药品/药物 Download PDFInfo
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- CN115701990A CN115701990A CN202080100373.XA CN202080100373A CN115701990A CN 115701990 A CN115701990 A CN 115701990A CN 202080100373 A CN202080100373 A CN 202080100373A CN 115701990 A CN115701990 A CN 115701990A
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Abstract
本发明涉及医学和兽医学,更具体地涉及药理学,并且可用于治疗由脂质包膜RNA病毒引起的病毒感染,特别是冠状病毒感染、艾滋病和丙型肝炎。本发明拓展了用于所声称目的的药物的范围。技术成果是发明了一种在细胞内具有抗菌作用的药物,所述药物激活人体和动物体内内源性甲醛的生成,所述药物没有副作用和毒性作用。所述技术成果是通过使用含有0.073‑0.075%甲醛的等渗氯化钠溶液的免疫调节药物以治疗冠状病毒、逆转录病毒感染和丙型肝炎实现的,所述药物为肌内注射剂,所述药物每次注射的单剂量为5mL。
Description
技术领域
本发明涉及医学和兽医学,更具体地涉及药理学,并且可用于治疗由脂质包膜RNA病毒引起的病毒感染,特别是冠状病毒感染、艾滋病和丙型肝炎。本发明拓展了实现所要达到目的的方法库。
背景技术
治疗丙型肝炎的药物是已知的(参见2005年01月20日公开的专利No.RF2244554,IPC分类号为A61K35/78),包含白桦脂醇含量大于70%的桦树皮提取物和药学上可接受的载体。这种药用于患者口服。
由于该药物是一种草药制剂,是一种多元系,不仅可以刺激抗病毒保护,还可以改变人体和动物体内的平衡,导致潜在过敏患者、孕妇和哺乳期妇女对其组分产生过敏反应。应该注意的是,白桦脂醇与其他药物的相互作用尚未确定,但是,并不排除这种可能性。
已知一种来自高度纯化的酵母RNA提取物的组合物,其具有至少75%重量的25±10个核苷酸的片段,纯度优选为至少99%,与甘露醇以2:1至3:1的重量比组合(参见2016年09月10日公开的专利No.RF2597150,IPC分类号为A61K31/7105),而酵母RNA提取物占组合物重量的至少50%。该组合物用于治疗由正粘病毒科病毒、副粘病毒、肝炎、疱疹病毒科病毒以及肠道病毒和腺病毒引起的病毒性疾病。此外,修饰的酵母RNA能够抑制流感病毒、丙型肝炎病毒、生殖器疱疹病毒、人类免疫缺陷病毒和柯萨奇病毒B组的繁殖。
然而,这种药物不能完全消除所有这些病毒,只能降低病毒载量,例如,在病毒性丙型肝炎中。此外,如此严重地干扰RNA,必定会影响机体的稳态。
已知一种用于治疗严重型病毒感染的片剂组合物(参见2015年08月10日公开的专利No.RF2559179,IPC分类号为A61K9/10),包含选自重组人干扰素-α、重组人干扰素-β、重组人干扰素-γ的重组人干扰素;选自美昔得乐、emoxipin、dibunol、α-硫辛酸和康胃素的抗氧化剂;选自乙酰半胱氨酸、半胱氨酸、赖氨酸、精氨酸的氨基酸;选自乳清酸钾、riboxin、甲基尿嘧啶以及成形碱的合成代谢作用再生剂。
然而,当使用这种化合物制剂时存在一些限制。肝病、严重抑郁症和/或有自杀倾向史、癫痫和妊娠者应慎用本品。接受抗惊厥药治疗的患者、根据NYHA分级患有III-IV级心力衰竭的患者以及患有心肌病、骨髓功能障碍、贫血或血小板减少症的患者在使用该药物治疗时必须谨慎。
已知一种抗流感的防腐剂(参见2009年05月20日公开的专利No.RF2355391,IPC分类号为A61K31/045),其含有阳离子表面活性剂、低分子量乙二醇或甘油、铵盐和组合物、尿素,以及以铵盐形式存在的硝酸铵,这些成分具有一定的比例。用十二烷基二甲基溴化铵或十二烷基二甲基氯化铵作为阳离子表面活性剂。用三甘醇或1,2-丙二醇或聚丙二醇作为低分子量乙二醇。用水或8-20%的乙醇或异丙醇水溶液作为成分。本发明提高了目标产品在长期储存过程中的生物杀灭活性,扩大了作用范围,降低了刺激性和毒性。
然而,这种药物只能用来杀死体外的病毒。这种药物应该不能用于治疗病毒性疾病。
还已知一种用于预防和治疗由含RNA病毒(优选甲型流感病毒或鼻病毒)引起的病毒感染的药物(参见2014年07月27日公开的专利No.RF2524304,IPC分类号为А61М15/00)。该药物含有o-乙酰水杨酸盐作为活性成分,以及选自赖氨酸、精氨酸、鸟氨酸和二氨基丁酸的氨基酸作为目标添加剂。该药物旨在通过口鼻吸入的气雾剂施用。
这种药物的主要缺点是使用乙酰水杨酸可能会对呼吸道造成严重刺激。甚至在o-乙酰水杨酸盐与氨基酸的复合物的帮助下降低这种可能性,也不能完全排除过敏反应的可能性。
当使用该组合物时,具有以下病史的人存在高风险:荨麻疹、摄入乙酰水杨酸和其他NSAID引起的鼻炎、血友病、出血性素质、低凝血酶原血症、主动脉夹层动脉瘤、门静脉高血压、维生素K缺乏症、肝和/或肾功能不全、葡萄糖-6-磷酸脱氢酶缺乏症、雷耶氏综合征(Reye Syndrome)、儿童期(15岁以下-病毒性疾病背景下体温过高的儿童患有雷耶氏综合征的风险)、对乙酰水杨酸和其他水杨酸过敏。
乙酰水杨酸,即使是小剂量,也会减少体内尿酸的排泄,这可能会导致易患痛风的患者急性发作。
应该注意的是,乙酰水杨酸经常与其他药物相互作用,例如,与钙通道阻滞剂、限制钙摄入或增加钙从体内排泄的药物相互作用;或利尿剂(螺内酯、速尿等)的效率降低。
最接近所要求保护的是包含活性成分和靶向添加剂的免疫调节剂(参见1997年04月27日公开的专利No.RF2077882,IPC分类号为A61K 31/115)。作为活性成分,它含有甲醛、氯化钠和蒸馏水作为目标添加剂,同时它是一种含有:甲醛0.07wt.%-0.24wt.%、氯化钠0.9wt.%-0.95wt.%、蒸馏水-余量至100wt.%的注射溶液。
这些类似物表明,抗病毒药物的设计远未解决问题。因此,寻找预防病毒感染的新方法非常重要。
发明内容
本发明的技术问题是提供一种有效的注射剂,用于治疗由人类和动物中含RNA的病毒引起的感染,以及扩大抗冠状病毒感染、逆转录病毒感染和丙型肝炎的药物库。
技术成果是设计了一种在细胞内具有抗菌作用的药物,所述药物激活人体和动物体内内源性甲醛的生成,所述药物没有副作用和毒性作用。
所述技术效果是通过使用含有0.073-0.075%甲醛的等渗氯化钠溶液的免疫调节药物用于治疗冠状病毒感染、逆转录病毒感染和丙型肝炎实现的,所述药物为肌内注射剂,所述药物每次注射的单剂量为5mL。根据疾病的严重程度,所述药物按照不同的方案施用,即:每天1次,连续7天,或2次,第二次或在第一次注射后第7天或在第一次注射后一个月。可以在第一次注射后的第2天、第3天和第10天施用。在特别严重的情况下,每次注射间隔12小时,施用3次,然后在一天或两天后再施用5次,每次注射间隔为12小时,然后在最后一次注射后,一天施用一次,然后3天后进行第二次单次注射,在最后一次注射后5天,进行最后一次单次施用。
作者所知的专利和科技信息来源没有描述基于细胞内内源性甲醛生成的激活来治疗由含RNA病毒引起的病毒感染(特别是冠状病毒感染、艾滋病(AIDS)、人和动物的丙型肝炎)的方法的。它的新功能和提出的用途与它以前已知的特性并不一致。之前在任何地方都没有描述过该药物的施用方法。
目前,还没有一种通用的抗菌药物能够在不影响体内稳态的情况下消灭人体和动物体细胞内的传染病病原体(病毒)。现有的防腐剂通常用于灭活外部环境中的病原体。
人们最感兴趣的是甲醛(福尔马林),它是自然界中最简单的化合物之一。该物质被归类为化学性质的无菌药物(有机化合物),用于破坏外部环境中的传染病病原体,作为组织学和病理解剖学中细胞和组织的化学防腐剂。
现已证实,生物体内存在内源性甲醛,是一种天然代谢产物,参与机体的许多生化反应。内源性甲醛的浓度可能达到0.2-0.5mM,其在血液中的含量可能为0.05-0.1mM(M.Casanova,H.D.Heck,J.I.Everitt,W.W.Harrington,J.A.Popp.Formaldehydeconcentrations in the blood of Rhesus monkeys after inhalation exposure//FoodChem.Toxicol.Int.J.Publ.Br.Ind.Biol.Res.Assoc.1988,26,715;X.Song,X.Han,F.Yu,J.Zhang,L.Chen,C.Lv,A reversible fluorescent probe based on C=Nisomerization for the selective detection of formaldehyde in living cells andin vivo.//The Analyst 2018,143,429;Human Endogenous Formaldehyde as anAnticancer Metabolite:Its Oxidation Downregulation May Be a Means ofImproving Therapy Yuri L.Dorokhov Ekaterina V.Sheshukova Tatiana E.BialikTatiana V.Komarova//BioEssays 2018,1800136)。众所周知,甲醛很容易渗透到所有细胞中,并且当其浓度超过其生理常态时很容易被去除。由于细胞酶在三种不同的途径中氧化甲醛,包括P450单加氧酶、线粒体AlDH2和编码ADH5或甲醛脱氢酶的基因,因此,体内甲醛的生理水平保持恒定,(Dorokhov Y.L.Metabolic methanol:molecular pathways andphysiological role//Physiol.Rev.2015.95(2),603–644;Yuri L.Dorokhov EkaterinaV.Sheshukova Tatiana E.Bialik Tatiana V.Komarova Human EndogenousFormaldehyde as an Anticancer Metabolite:Its Oxidation Downregulation May Bea Means of Improving Therapy//BioEssays 2018,1800136)。在甲烷和甲基丙烯酸甲酯的二卤衍生物的生物转化过程中,在微粒体二甲基酶的作用下,在肝脏中形成甲醛(Malyutina N.N.,Taranenko L.A.Pathophysiological and clinical aspects of theeffects of methanol and formaldehyde on the human body//Modern problems ofscience and education.–2014.–No.2[Russ.];URL:http://science-education.ru/ru/article/view?id=12826(访问日期:2020年3月17日)。人体利用甲醛合成胸苷、嘌呤和其他酸;它是在丝氨酸和其他氨基酸(在较小程度上)被破坏时形成的。当它通过一系列酶转化进入血液时,它在肝脏中被氧化成甲酸,而在肝脏中形成甲醇。此外,甲酸在甲酸脱氢酶的作用下代谢为CO2,或参与四氢叶酸系统中一碳残基的交换。甲醛容易与蛋白质、胺、酰胺、核蛋白和核酸相互作用(MalyutinaN.N.,Taranenko L.A.Pathophysiological andclinical aspects of the effects of methanol and formaldehyde on the humanbody//Modern problems of science and education.–2014.–No.2[Russ.];URL:http://science-education.ru/ru/article/view?id=12826(访问日期:2020年3月17日)。
人类和动物的所有体液中都有少量的这种物质,其仅在尿液中比血液中多20%,这表明了其从体内排出的主要方式。
研究表明,低浓度甲醛(如10mmol/L)可促进HeLa细胞增殖。然而,当甲醛浓度达到62.5mmol/L时,其抑制细胞生长。
一定浓度的甲醛对于体内细胞的生命活动很重要,因为内源性甲醛是一种重要的代谢产物,然而,在其浓度显著增加的情况下,其也可能成为基因毒素(RichardJ.Hopkinson,Christopher J.Schofield.Deciphering Functions of IntracellularFormaldehyde:Linking Cancer and Aldehyde Metabolism//Biochemistry 2018,57,6,904–906)。
以属于冠状病毒的猪传染性胃肠炎病毒为例,已发现浓度为0.01%的福尔马林可灭活该病毒(Stepanek J.,Mensik J.,Pospisil Z.,Rozkony V.Vlev formalinu abetapropiolaktonuna infekcnost a antigenicitu puvodce virovegastroenterit duprasat(VGR).//Veter.Med.(CSSR).–1973.–V.18.–#5.–P.269–280)。在37℃的福尔马林的作用下,该病毒在150分钟后就失去了其致病性(Bohl E.H.Transmissiblegastroenteritis virus(classical enteric variant).//VirusInfec.Procines.Amsterdam ect.–1989.–P.139–153)。其他冠状病毒(小鼠肝炎病毒、鸡传染性支气管炎病毒、猫传染性腹膜炎病毒、牛胃肠炎和呼吸道感染病毒、人胃肠炎病毒等。)对甲醛也很敏感。
所发明的药物是在等渗氯化钠溶液中的甲醛溶液,使用常规制备方法获得,将超低剂量的活性成分溶解在载体中,并且所使用的浓度在正常细胞没有毒性作用。
所述药物对身体有复杂的影响,有助于维持体内平衡。所述药物属于一类新的药物,可促进抗原特异性免疫反应的激活,所述药物能够从体内完全消除感染源。
我们认为,胃肠外施用外源性甲醛(福尔马林)会导致其在人体淋巴和血液中的浓度增加。这反过来又破坏了甲醛从身体细胞向细胞间隙的流出,从而导致细胞内的甲醛含量增加,这符合勒夏特列-布朗定律(Le Chatelier–Brown’s rule)之一,该定律指出,随着一种生成物浓度的增加,平衡向反应物的方向移动(向左)。因此,细胞内的病毒失活。
甲醛的水溶液是一种透明、无色的液体,具有特殊的刺激性气味,可与水和醇以任何比例混溶。
甲醛(НСОН)是醛类的代表。它是一种无色气体,有刺激性气味,摩尔重量为30.03,20℃时密度为0.815,熔点为92℃,沸点为19.2℃,易溶于水、酒精。
等渗氯化钠注射液是一种无色透明的咸味液体,氯化钠浓度为0.85-0.95%。该溶液是无菌、无热原的。
氯化钠是立方晶体或白色结晶粉末,有咸味,无气味。可溶于水(1:3)。
所要求保护的药物是透明、无色、无气味的液体,具有轻微的咸味。
所述药物的制备如下。
取2份(按重量计)浓度为36.5-37.5%的甲醛医用溶液,将其加入998份(按重量计)浓度为0.85-0.95%的无菌氯化钠注射液中,直至药物中甲醛的浓度为0.073-0.075%。该产品储存在温度为15-35℃的避光处。
具体实施方式
实施例1取0.2mL 37%的医用甲醛溶液,加入99.8mL 0.9%(或0.95%)无菌等渗氯化钠溶液中。充分搅拌溶液混合物。所得产物中甲醛的最终浓度为0.074wt.%。
实施例2取0.2mL 36.5%的医用甲醛溶液,加入99.8mL0.9%(或0.95%)无菌等渗氯化钠溶液中。充分搅拌溶液混合物。所得产物中甲醛的最终浓度为0.073wt.%。
实施例3
通过用14C-标记的甲醛孵育细胞,研究了外源甲醛激活内源性甲醛产生的能力。使用比活度为1.7TBq/M、体积活度为10.1GBq/L(5.9mM溶液)、放射化学纯度为98%的标记甲醛。用新鲜的37%甲醛(美国Sigma)以获得所需浓度的溶液。
未用放射性标记的甲醛孵育的细胞样品作为阴性对照。
在Tri-Carb 2800TRβ-计数仪(美国PerkinElmer)上用ULTIMA GOLD LLT闪烁液(scintillator)(美国PerkinElmer)测定样品的放射性。将一份样品(0.1mL)与闪烁液(0.9mL)充分混合,并在制备混合物后2小时内测定放射性。
在48孔聚苯乙烯板的表面上孵育细胞。
原代人牙龈成纤维细胞和宫颈癌HeLa细胞用作细胞培养物。在37℃、6%CO2环境下,在补充了10%胎牛血清和抗生素(青霉素和链霉素)的IMDM培养基中孵育细胞。
在实验过程中,将细胞置于孔直径为1cm的48孔聚苯乙烯板中,每孔12000个细胞,每种类型的样本一式三份(在0.5ml培养基中)。接种细胞后孵育24小时后,除去培养基,用0.5mL生理盐水冲洗细胞,将不含或含甲醛的生理盐水加入对照和实验孔中,与细胞一起孵育30分钟、1小时和2小时(最终浓度为0.11%、0.074%、0.014%、0.0028%和0.00056%,五倍稀释,10000ppm/孔)。为了研究甲醛在培养基中的作用,将50μL(1/10体积)的甲醛生理盐水溶液加入到具有450μL培养基的对照和实验孔中(福尔马林的浓度比上述浓度高10倍,因此,获得的甲醛溶液的浓度与在盐水中孵育细胞的浓度相同)。孵育后,从上清液中取出两份100μL培养基(双倍)以测定引入的总的放射性,然后除去甲醛溶液,用磷酸盐缓冲液洗涤细胞两次,并用0.25%胰蛋白酶溶液(美国Sigma)处理,以便从培养物表面塑料分离细胞。通过以800g离心10分钟以沉淀细胞悬浮液,并从胰蛋白酶上清液中取出等分试样。将细胞沉淀重悬于220μL盐水中,并取2份100μL的等分试样来测量样品的放射性。
在获得样品的放射性数据后,根据比放射性和样品的初始体积计算部分中甲醛的百分比。基于甲醛溶液的比摩尔放射性来分析馏分中的甲醛浓度。
表1在盐水中孵育时,细胞内甲醛累积
*显示了平均值±平均值的误差。
**上清液的放射性为100%
从表1中可以看出,与在0.11%甲醛溶液中孵育细胞相比,将细胞与浓度为0.074%的溶解在盐水中的甲醛一起孵育,可分别激活原代人牙龈成纤维细胞和宫颈癌中内源性甲醛的产生激活18.4%和32%。
应该注意的是,当细胞与培养基中稀释的甲醛一起孵育时,获得了类似的结果。例如,与在0.11%甲醛溶液中孵育细胞相比,用0.074%甲醛溶液孵育细胞将原代人牙龈成纤维细胞和宫颈癌中内源性甲醛的产生分别激活20.6%和30.2%(表2)。
表2在培养基中孵育时,细胞内甲醛累积
*显示了平均值±平均值的误差。
**上清液的放射性为100%
因此,研究表明,与其他浓度(0.11%、0.028%、0.00052%和0.014%)相比,只有所用的0.074%甲醛能够激活原代人牙龈成纤维细胞和宫颈癌HeLa细胞中产生内源性甲醛,这符合勒夏特列-布朗定律之一,该定律指出,随着一种生成物(在本实施例情况下,浓度为0.074%的外源性甲醛)浓度的增加,平衡向增加细胞中反应物(内源性)甲醛的方向移动(向左)。因此,细胞内的病毒失活。
以下是使用所述药物治疗各种病毒感染的示例。
出于治疗目的,肌肉注射一次施用5mL所述药物,并且施用方案可以不同。即:
–根据第一种方案,所述药物分两次施用:第一次注射后的第1天和第7天;
–根据第二种方案,也是两次,但间隔一个月;
–根据第三种方案,在第一次注射后的第2天、第3天和第10天;
–根据第四种方案,施用3次,每次注射间隔12小时,然后在1-2天后再施用5次,每次注射间隔12小时。然后,在最后一次注射后一天,施用一次,然后在三天后进行重复单次注射,之后在最后一次注射后五天进行最后一次单次注射;以及
–根据第五种方案–每天1次,持续7天。
方案中的注射次数可根据疾病的严重程度而增加。
实施例4根据记载,猪冠状病毒感染(猪传染性胃肠炎)出现在母猪、哺乳仔猪和断奶仔猪中。
在不利于传染性胃肠炎的农场中,母猪分娩后表现出肺部疾病,根据记载,断奶仔猪中出现肺部和肠道疾病,乳猪中出现到肠道疾病。
在单间猪棚,对16头具有153头新生仔猪的母猪之类进行实验,其中记录了传染性胃肠炎。为此,制备0.074%的甲醛溶液。第一组动物(8头母猪和75头新生仔猪)以每头母猪5mL和每头仔猪2mL的剂量注射0.074%的甲醛溶液。对照组(8头母猪和78头新生仔猪)注射相同体积的盐水。施用两次所述药物,即:在第一次注射后的第一天和第七天。
对这些动物进行临床观察直至两周龄,记录传染性胃肠炎的临床表现和动物的死亡情况。所得结果见表3。
表3对母猪施用0.074%甲醛溶液的结果
我们的研究结果表明,向母猪和新生仔猪同时施用0.074%的甲醛溶液显著降低了哺乳仔猪传染性胃肠炎的发病率和死亡率。必须从两个角度来考虑两个环节链(母猪和新生仔猪)。对母猪的第一次施用减少了母猪体中病原体的数量,降低了新生仔猪的感染剂量。将这种药物引入仔猪体内产生了治疗效果。
从表中可以看出,发病率下降了50%(74.4-24.0),这与减少母猪体内病毒量的预防作用有关,并且由于给仔猪施用药物后的治疗效果,死亡率降低了6倍。
实施例5证明所述药物对逆转录病毒感染(艾滋病)的抗菌效果。本研究在6名志愿者上进行。
在第一次注射后的第2天、第3天和第10天,前五名患者以5mL的剂量施用所述药物,最后一名(第六名)患者以5mL的剂量施用两次所述药物,第二次是在第一次注射后一个月。
治疗结果:
患者1的初始病毒载量为750000RNA/mL,治疗后两个月的病毒载量为2187RNA/mL,注意到病毒载量降低了342倍。
患者2的初始病毒载量为150201RNA/mL,治疗后两个月的病毒载量为1230RNA/mL,注意到病毒载量降低了122倍。
患者3的初始病毒载量为97171RNA/mL,治疗后两个月的病毒载量为1101RNA/mL,注意到病毒载量降低了88倍。
患者4的初始病毒载量为78122RNA/mL,治疗后两个月的病毒载量为1037RNA/mL,注意到病毒载量降低了75倍。
患者5的初始病毒载量为78122RNA/mL,治疗后两个月的病毒载量为1837RNA/mL,注意到病毒载量降低了42.5倍。
患者6的初始病毒载量为11182RNA/mL,治疗后两个月的病毒载量为1165RNA/mL,注意到病毒载量降低了9倍。
所有患者的病毒载量都急剧下降,这是由于所述药物在细胞水平上的抗菌作用,而对身体没有负面影响,并且没有毒性作用。
实施例6所述药物对丙型病毒性肝炎的抗菌效果的证明。对10名志愿者进行了治疗。
所有患者都表现出病毒复制的复发性变化,病毒载量每1-3个月以1个十进制对数波动(周期性下降和上升)。有3名患者在疾病的血清阴性阶段开始治疗。
在7名患者中观察到病毒载量最小化,即:最终水平为1000RNA复制/mL,而初始水平为2500000RNA复制/mL。
3例患者在治疗开始时,在该病的血清阴性阶段发现PCR阴性。
所有病毒性肝炎患者的总体状况、睡眠、情绪都有所改善,效率提高,身体活动耐受性也有所改善。患者的社交活动增加,他们在家庭和工作中的关系改善。
实施例7患者M,46岁,SARS-CoV-2冠状病毒感染(基于病历、临床症状和X线照片)。
临床症状:高温(38-39.2℃)、持续干咳、呼吸衰竭伴胸痛、不适和中度头痛。
胸腔的X线照片:在肺野的周围部分存在小的炎症病灶。
用抗生素治疗三天没有效果。
根据以下方案进行处理。以5mL的剂量施用所述药物。每12小时注射三次所述药物,然后一天后每12小时注射五次所述药物。然后一天后注射一次所述药物,三天后注射另一次,最后一次注射在前一次注射后五天进行。
结果:临床症状消失;X光片上没有炎症病灶。所述药物没有副作用和毒性作用。
实施例8患者S,35岁-冠状病毒感染(基于病历和临床症状)。
临床症状:体温37.2-37.7℃,持续干咳,身体不适,中度头痛。该患者曾与确诊为冠状病毒感染的人接触。用抗生素治疗10天没有效果。
根据以下方案进行一个疗程的治疗:以5mL的剂量肌肉注射,每天一次,持续7天。
结果:临床症状消失,完全康复。注意到所述药物没有副作用和毒性作用。
实施例9患者S,56岁,被诊断为新冠肺炎(PCR方法)。
治疗开始时的临床症状:体温39.2℃,根据计算机断层扫描(CT)显示双侧肺损伤(每侧25%),干咳,胸痛,全身无力,出汗,无嗅觉。从患病的第一天起,他就服用抗生素,但没有明显效果。
在疾病的第3天,根据以下方案开始用所述药物进行治疗:以每天5mL的剂量施用药物,持续7天,间隔24小时。不再使用任何抗生素。
结果
第2天咳嗽加剧,转为湿性期(wet stage)。体温降至37.4℃,头痛消失。在治疗开始后的第3天,体温恢复正常(36.6℃),所有疼痛症状消失。总体情况有所改善。病人感到精力充沛,没有出汗。在第7天,患者客观地记录了已完全康复。
在用所述药物开始治疗后的第14天,进行肺部的CT扫描。根据检查结果得出的结论是“健康”。没有发现炎症或残留症状。对照PCR检测为阴性。
实施例10患者R,46岁,被诊断为新冠肺炎(PCR方法)。
治疗开始时的临床症状:体温39.6℃,根据CT显示双侧肺损伤(分别为20%和30%),干咳,胸骨后疼痛,全身无力,出汗,持续头痛,无嗅觉。
在病后的第5天开始用所述药物治疗。每天施用5mL,连续7天,间隔24小时。不再使用任何抗生素。
结果
在用所述药物开始治疗的第2天,咳嗽加剧并进入湿性期。体温降至37.0℃,头痛消失。在治疗开始后的第3天,体温恢复正常(36.6℃),所述疼痛症状消失。总体情况有所改善。患者注意到肺部有痰排出,体力激增,没有出汗。在第7天,客观上,患者录得完全康复。
在用所述药物开始治疗后的第14天,进行肺部的CT扫描。根据检查结果得出的结论是“健康”。没有发现炎症或残留症状。对照PCR检测为阴性。
因此,所述药物在细胞内具有杀菌作用,在没有副作用和毒性作用的情况下,激活人和动物体内内源性甲醛的产生。
Claims (5)
1.含有0.073-0.075%甲醛的等渗氯化钠溶液的免疫调节药物在治疗冠状病毒、逆转录病毒感染和丙型肝炎中的应用,所述药物为肌内注射剂,所述药物每次注射的单剂量为5mL。
2.根据权利要求1所述的药物的应用,所述药物每天施用1次,持续7天。
3.根据权利要求1所述的药物的应用,所述药物注射2次,所述第二次注射是在第一次注射后的第7天或第一次注射后1个月。
4.根据权利要求1所述的药物的应用,所述药物在第一次注射后的第2天、第3天和第10天注射。
5.根据权利要求1所述的药物的应用,所述药物注射3次,所述药物的每次注射间隔12小时,然后在一天或两天后注射5次,每次注射间隔12小时,然后在最后一次注射后的第二天进行单次注射,然后在3天后进行重复的单次注射,并且在最后一次注射后5天进行所述药物的最后一次单次施用。
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PCT/RU2020/050334 WO2021194375A1 (ru) | 2020-03-26 | 2020-11-19 | Средство для лечения коронавирусных, ретровирусных инфекций и гепатита с |
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