CN1798553A - 冠状病毒灭活剂 - Google Patents

冠状病毒灭活剂 Download PDF

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Publication number
CN1798553A
CN1798553A CNA200480015086XA CN200480015086A CN1798553A CN 1798553 A CN1798553 A CN 1798553A CN A200480015086X A CNA200480015086X A CN A200480015086XA CN 200480015086 A CN200480015086 A CN 200480015086A CN 1798553 A CN1798553 A CN 1798553A
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myramistin
coronavirus
inactivating agent
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CN100350904C (zh
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尤鲁·谢苗诺维奇·克里沃舍因
阿多莉娜·彼得罗夫娜·鲁德科
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MEGAINPHARM GmbH
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/16Amides, e.g. hydroxamic acids
    • A61K31/165Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • A61P31/14Antivirals for RNA viruses

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Virology (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

本发明涉及一种miramistine(别名肉豆蔻酰胺-丙基-二甲基-苄基-氯化铵)形式的新的冠状病毒灭活剂,其以前已知作为表现抗真菌和抗微生物作用和针对HIV、流感和疱疹病毒感染有效的防腐剂。所述发明扩展了用于所述应用的活性剂的范围,并且使得治疗和预防由所述冠状病毒引起的呼吸道疾病(包括SARS)和胃肠炎成为可能。

Description

冠状病毒灭活剂
本发明涉及医学和药学工业,并可以用于治疗和预防药物的发现、生产和应用。
脂质溶剂(liposolvent)、洗涤剂和防腐剂已知是用于灭活冠状病毒的药物(L.Ya.Zakstel’skaya,A.V.Scheboldov//Human and animalcoronaviruses;Medicine,Moscow,1977,vol.2,p.221;General andparticular virology,V.M.Jdanov and S.Ya.Gaidamovich编辑,Medicine,Moscow,1982,vol.2,p.316-339;A.I.Korotyaev,S.A.Babichev//Medicinal microbiology,virology and immunology,Saint-Petersburg:《Special literature》,1998,p.273)。
我们提出了肉豆蔻酰氨基丙基二甲基苄基氯化铵(myramistin,发明人证书1832496)用于灭活冠状病毒的应用。以前这一化合物已知作为用于传统性病如梅毒、滴虫病、淋病的预防药和作为用于化脓炎症性角膜疾病(pyoinflammatory comea disease)的防腐剂(R.F.Patent2164135)。
本发明要求保护的技术方案增加了用于预防和治疗冠状病毒引起的疾病的药物的数目。
下面所给出的实施例证明了本发明的化合物的灭活效果(其中“Myramistin”用作化合物的名称以便于叙述的简单化)。
实施例1:
根据下述方案测定了对于人胚胎肾细胞培养物(体外),Myramistin对冠状病毒测试培养物(人冠状病毒OC43)的最小抑制浓度(MIC):
 第1阶段   测试病毒+Myramistin(以相应的浓度)
 第2阶段   温育(2小时)
 第3阶段   将中和剂(例如25%胎牛血清)加入反应混合物中并温育10-20分钟
 第4阶段   感染敏感细胞培养物(例如人胚胎肾细胞培养物)
 第5阶段   培养(5-8天)
 第6阶段   记录基于血细胞吸附现象和细胞吞噬活性(cytophaticactivity)-共质体形成(symplastoformation)的结果
对四种化合物制剂进行了三个系列的实验。基于得到的结果计算Myramistin对冠状病毒的最小抑制浓度。实验数据在下表1中给出。
表1.Myramistin和其它防腐剂对人冠状病毒OC43的体外MIC
  防腐剂   MIC(%)
  Myramistin   0.01±0.005
  Decamethoxin   0.1±0.05
  洗必泰   0.05±0.005
  Etonium   0.5±0.2
  Dioxydine   R
  Rockal   0.1±0.05
  壬苯聚醇-9   0.2±0.09
  吐温-20(Twin-20)   2.0±0.8
注:R-冠状病毒对高于2.5%的防腐剂浓度具有耐药性。
从获得的结果(表1)可见,就冠状病毒灭活而言,与所有已知和目前使用的防腐剂相比,myramistin更有效。
实施例2:
根据下述方案进行对于幼鼠,myramistin对人冠状病毒OC43的体内MIC的测定
 第1阶段   测试病毒+Myramistin(以相应的浓度)
 第2阶段   温育(30分钟)
 第3阶段   感染幼鼠脑或腹腔
 第4阶段   记录感染后2-3天的结果(动物被膜(coverlet)充血、震颤、肌肉强直、无吸吮、死亡)
对不同浓度的四种化合物制剂(每种制剂6只小鼠)进行三个系列的实验。以1gLD50评价病毒对幼鼠的感染进展。平均实验数在表2中给出。
表2.Myramistin对人冠状病毒OC43的感染活性的影响结果(MIC浓
               度)(体内,幼鼠)
  系列号             病毒的感染活性(lgLD50)
  治疗前           用相应剂量治疗后(%)
  0.0001   0.001   0.005   0.01
  1   6.4   3.6   1.0   0   0
  2   6.0   3.2   1.0   0   0
  3   6.3   3.0   1.2   0   0
得到的结果清楚地表明,0.0001%浓度的myramistin的存在几乎使病毒的活性降低一半,而且0.005%和更高的浓度完全中和了病毒的活性。
实施例3:
基于用鸡红细胞的血凝反应(HGR)评价myramistin对冠状病毒OC43的血凝活性的影响
将浓度0.000001至0.001%的Myramistin溶液加入含有血凝滴度不小于1∶512的冠状病毒OC43的培养肉汤中。温育30分钟后,加入25%的胎牛血清以中和myramistin,然后10-20分钟后进行鸡血细胞的HGR。对不同浓度(每种浓度3例)的四种myramistin制剂进行四个系列的实验。平均实验数在表3中给出。
表3.Myramistin对冠状病毒OC43的血凝活性影响的实验结果
  系列号                  以滴度表示的血凝活性
  治疗前              用相应剂量治疗后(%)
  0.000001   0.00001   0.0001   0.001
  1   512   8   4   0   0
  2   2048   16   8   0   0
  3   1024   8   4   0   0
  4   2560   16   8   0   0
从上述的实验结果可见,myramistin以比对冠状病毒的感染活性(0.0001%)更低的浓度(0.000001%)实现对冠状病毒血凝素(其使得冠状病毒吸附在敏感细胞上)的影响。
获得的实验数据清楚地证明所提出的技术方案使得可以将肉豆蔻酰氨基丙基二甲基苄基氯化铵(《myramistin》)用于灭活冠状病毒,并可用于开发治愈由冠状病毒引起的疾病的新预防药和治疗药。

Claims (1)

1.肉豆蔻酰氨基丙基二甲基苄基氯化铵(《myramistin》)用于灭活冠状病毒的应用。
CNB200480015086XA 2003-06-04 2004-06-03 冠状病毒灭活剂 Expired - Fee Related CN100350904C (zh)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102869354A (zh) * 2010-02-19 2013-01-09 梅根医药股份有限公司 包含肉豆蔻酰氨基丙基二甲基苄基氯化铵的药物制剂
CN116390908A (zh) * 2020-03-05 2023-07-04 生态合成股份有限公司 抗病毒治疗

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102008039254A1 (de) * 2008-08-20 2010-02-25 Megainpharm Gmbh Arzneimittel
WO2014175757A1 (ru) 2013-04-22 2014-10-30 Общество с ограниченной ответственностью "Нанобиотех" Антисептический ветеринарный препарат и способы его использования

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US2459062A (en) * 1944-02-08 1949-01-11 American Cyanamid Co Quaternary ammonium compounds
SU1796185A1 (ru) * 1990-06-23 1993-02-23 Adolina P Rudko Фунгицид 2
US5244922A (en) * 1990-09-04 1993-09-14 Burzynski Stanislaw R Methods for treating viral infections
WO1993000892A1 (en) * 1991-07-10 1993-01-21 Jury Semenovich Krivoshein Pharmaceutical preparation

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102869354A (zh) * 2010-02-19 2013-01-09 梅根医药股份有限公司 包含肉豆蔻酰氨基丙基二甲基苄基氯化铵的药物制剂
CN102869354B (zh) * 2010-02-19 2015-12-16 梅根医药股份有限公司 包含肉豆蔻酰氨基丙基二甲基苄基氯化铵的药物制剂
CN116390908A (zh) * 2020-03-05 2023-07-04 生态合成股份有限公司 抗病毒治疗

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WO2004108125A1 (fr) 2004-12-16
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KR20060054190A (ko) 2006-05-22
EP1634590A4 (en) 2009-04-08
RU2234313C1 (ru) 2004-08-20

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