CN100350904C - 冠状病毒灭活剂 - Google Patents

冠状病毒灭活剂 Download PDF

Info

Publication number
CN100350904C
CN100350904C CNB200480015086XA CN200480015086A CN100350904C CN 100350904 C CN100350904 C CN 100350904C CN B200480015086X A CNB200480015086X A CN B200480015086XA CN 200480015086 A CN200480015086 A CN 200480015086A CN 100350904 C CN100350904 C CN 100350904C
Authority
CN
China
Prior art keywords
myramistin
coronavirus
inactivating agent
concentration
stage
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
Application number
CNB200480015086XA
Other languages
English (en)
Other versions
CN1798553A (zh
Inventor
尤鲁·谢苗诺维奇·克里沃舍因
阿多莉娜·彼得罗夫娜·鲁德科
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
MEGAINPHARM GmbH
Original Assignee
MEGAINPHARM GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by MEGAINPHARM GmbH filed Critical MEGAINPHARM GmbH
Publication of CN1798553A publication Critical patent/CN1798553A/zh
Application granted granted Critical
Publication of CN100350904C publication Critical patent/CN100350904C/zh
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses

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 cornea 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lgLD50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在生产用于灭活冠状病毒的药物中的应用。
CNB200480015086XA 2003-06-04 2004-06-03 冠状病毒灭活剂 Expired - Fee Related CN100350904C (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
RU2003116391/15A RU2234313C1 (ru) 2003-06-04 2003-06-04 Средство инактивации коронавирусов
RU2003116391 2003-06-04

Publications (2)

Publication Number Publication Date
CN1798553A CN1798553A (zh) 2006-07-05
CN100350904C true CN100350904C (zh) 2007-11-28

Family

ID=33414532

Family Applications (1)

Application Number Title Priority Date Filing Date
CNB200480015086XA Expired - Fee Related CN100350904C (zh) 2003-06-04 2004-06-03 冠状病毒灭活剂

Country Status (5)

Country Link
EP (1) EP1634590A4 (zh)
KR (1) KR20060054190A (zh)
CN (1) CN100350904C (zh)
RU (1) RU2234313C1 (zh)
WO (1) WO2004108125A1 (zh)

Families Citing this family (4)

* 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
WO2011100994A1 (de) 2010-02-19 2011-08-25 Megainpharm Gmbh Arzneimittel enthaltend myramistin
WO2014175757A1 (ru) 2013-04-22 2014-10-30 Общество с ограниченной ответственностью "Нанобиотех" Антисептический ветеринарный препарат и способы его использования
GB202003240D0 (en) 2020-03-05 2020-04-22 Ecosynth Nv Antiviral treatment

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5244922A (en) * 1990-09-04 1993-09-14 Burzynski Stanislaw R Methods for treating viral infections

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
AU2493792A (en) * 1991-07-10 1993-02-11 Jury Semenovich Krivoshein Pharmaceutical preparation

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5244922A (en) * 1990-09-04 1993-09-14 Burzynski Stanislaw R Methods for treating viral infections

Also Published As

Publication number Publication date
EP1634590A4 (en) 2009-04-08
CN1798553A (zh) 2006-07-05
RU2234313C1 (ru) 2004-08-20
KR20060054190A (ko) 2006-05-22
EP1634590A1 (de) 2006-03-15
WO2004108125A1 (fr) 2004-12-16

Similar Documents

Publication Publication Date Title
KR20140050608A (ko) 유해 미생물 저해 방법 및 그를 위한 장벽-형성 조성물
CN1961679A (zh) 一种复方抗病毒喷雾剂及其制备方法
CN100350904C (zh) 冠状病毒灭活剂
CN1505478A (zh) 杀病毒组合物
EP2529737A1 (en) Antibacterial combination therapy
WO2020240472A1 (en) Wide-spectrum antibacterial pharmaceutical formulations comprising lysozyme and methods of using the same
US20230019880A1 (en) Compositions
RU2398596C2 (ru) Способы профилактики и лечения заболеваний, вызванных вирусом гриппа птиц a/h5n1, с использованием индуктора интерферона и ингибитора нейраминидазы
WO2006099376A1 (en) Dragon's blood anti-viral materials and methods
CN112843073A (zh) 瑞德西韦（Remdesivir）在制备抗牛副流感病毒3型药物中的应用
RU2480219C1 (ru) Способ лечения оспы
RU2753609C1 (ru) Противовирусное гуминовое средство
US9918933B2 (en) Medicine for treatment or adjuvant treatment of acquired immunodeficiency syndrome, preparation method therefor and use method thereof
RU2502512C2 (ru) Способ лечения гриппа птиц
CN113318115B (zh) 美他环素在制备防治牛副流感病毒3型病毒感染药物中的应用
RU2790837C2 (ru) Спрей для лечения инфицированных и неинфицированных ран при сахарном диабете i типа
US20220071902A1 (en) Solution and method for reducing the virulence of viruses, bacteria, yeasts, or fungus
Verona Adaptive, randomized, placebo-controlled trial to evaluate the efficacy of monoclonal antibodies in outpatients with mild or moderate COVID-19 (MANTICO)
RU2304969C2 (ru) Способ коррекции антиинфекционной резистентности организма при гнойно-воспалительных процессах кандида-бактериальной этиологии на фоне экспериментальной ожоговой травмы
RU2458138C2 (ru) Способ моделирования предупреждения формирования госпитальных штаммов
CN107648249B (zh) 去半乳糖替告皂甙在制备防治流感病毒感染的药物中的应用
Ghosh et al. Clays in the Global War Against COVID-19: Why are They Preferable Over the Conventional Weaponry?
RU2377006C1 (ru) Препарат, содержащий стафилококковый бактериофаг в качестве препарата для лечения кандидоза
WO2022226613A1 (pt) Formulação para enxaguante bucal com ação inibidora do vírus sars-cov-2 e redutora das patologias relacionadas
WO2022226614A1 (pt) Formulação para solução nasal com ação inibidora do vírus sars-cov-2 e das patologias relacionadas

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
C17 Cessation of patent right
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20071128

Termination date: 20100603