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WO2021212269A1 - Application of ellagic acid in preventing and treating novel coronavirus infection - Google Patents

Application of ellagic acid in preventing and treating novel coronavirus infection Download PDF

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Publication number
WO2021212269A1
WO2021212269A1 PCT/CN2020/085615 CN2020085615W WO2021212269A1 WO 2021212269 A1 WO2021212269 A1 WO 2021212269A1 CN 2020085615 W CN2020085615 W CN 2020085615W WO 2021212269 A1 WO2021212269 A1 WO 2021212269A1
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Prior art keywords
ellagic acid
compound
products
preventing
infection
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Ceased
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PCT/CN2020/085615
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French (fr)
Chinese (zh)
Inventor
盛军
王宣军
黄业伟
徐欢欢
朱强强
吴晓云
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Kunming Biological Manufacturing Research Institute Co Ltd
Yunnan Daye Dihong Biotechnology Co Ltd
Yunnan Agricultural University
Original Assignee
Kunming Biological Manufacturing Research Institute Co Ltd
Yunnan Daye Dihong Biotechnology Co Ltd
Yunnan Agricultural University
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Priority to PCT/CN2020/085615 priority Critical patent/WO2021212269A1/en
Publication of WO2021212269A1 publication Critical patent/WO2021212269A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P1/00—Disinfectants; Antimicrobial compounds or mixtures thereof
    • A—HUMAN NECESSITIES
    • A41—WEARING APPAREL
    • A41D—OUTERWEAR; PROTECTIVE GARMENTS; ACCESSORIES
    • A41D13/00—Professional, industrial or sporting protective garments, e.g. surgeons' gowns or garments protecting against blows or punches
    • A41D13/05—Professional, industrial or sporting protective garments, e.g. surgeons' gowns or garments protecting against blows or punches protecting only a particular body part
    • A41D13/11—Protective face masks, e.g. for surgical use, or for use in foul atmospheres
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/10—Washing or bathing preparations

Definitions

  • the present invention belongs to the field of medical technology, and in particular, relates to a class of compounds for highly effective and specific prevention and treatment of novel coronavirus infections and their applications.
  • New type of coronavirus pneumonia is a type of acute infectious disease caused by the 2019 new type of coronavirus (2019-nCoV) infection.
  • 2019-nCoV 2019 new type of coronavirus
  • the main symptoms include respiratory symptoms, fever, cough, shortness of breath, and difficulty breathing.
  • the infection can lead to pneumonia, severe acute respiratory syndrome, kidney failure, and even death.
  • isolation treatment and symptomatic and supportive treatment are the main ones.
  • the purpose of the present invention is to provide a class of compounds that can effectively and specifically prevent viral infections, especially high-efficiency and specific prevention and control.
  • Compounds infected by the new coronavirus can weaken the infectivity of the new coronavirus, thereby efficiently and specifically preventing the infection of the new coronavirus and reducing the risk of human-to-human transmission.
  • the main components of the compound include ellagic acid and ellagic acid derivatives.
  • the ellagic acid derivatives include but are not limited to ellagic acid methylation products and ellagic acid. Structural modifications and the like.
  • the compound is prepared from extracts from fruits such as blackberry, red berry, blueberry, pomegranate, etc. or chemically synthesized.
  • the effective concentration range of the compound is 1-1000ug/ml or 1-1000ug/g.
  • the product includes drugs, medical equipment, health products, disinfection products or protective products;
  • the forms of the drugs or health products include, but are not limited to, tablets, granules, hard capsules, soft capsules, oral liquids, and powders. , Mixtures, pills, dripping pills, sprays, aerosols, powder mists, eye drops, toothpaste, mouthwashes, facial masks, hand creams;
  • the disinfection products include but are not limited to soap, hand sanitizer, disinfectant , Disinfecting gel, wet tissues, laundry detergent, masks, etc.
  • the present invention provides a class of compounds that can specifically target the novel coronavirus.
  • the effective ingredients of the compound include ellagic acid, ellagic acid derivatives (including but not limited to ellagic acid methylation products, ellagic acid structural modifications, etc.) Analogs), the effective use concentration range is 10ng/ml to 1000ug/ml or 10ng/g to 1000ug/g.
  • the compound is used for product development, and the developed product is used to prevent and treat the infection of the new coronavirus, which can specifically weaken the infection ability of the new coronavirus, thereby preventing the infection of the new coronavirus and reducing the risk of human-to-human transmission.
  • the present invention is a medicine, medical device, health care product or disinfectant product containing a class of effective ingredients of a compound that has high efficiency and specificity to prevent and treat new coronavirus infections.
  • the disinfectant gel is added with ellagic acid within the effective concentration range, and the added disinfectant gel can effectively reduce the residue of the new coronavirus on the skin surface, thereby reducing the risk of infection.
  • Ellagic acid in the effective concentration range is added to the interlayer of the mask to effectively isolate the new crown virus on the outside of the mask from entering the respiratory system through respiration.
  • the hand cream is added with compounds within the effective concentration range. After the added hand cream is applied to the surface of the skin, it can effectively remove the residues of the new crown virus on the hands and effectively remove the residues on the skin surface, thereby reducing the risk of infection.
  • the disinfectant is added with compounds within the effective concentration range and released into the environment by spraying, reducing the infectious ability of the new coronavirus in the environment and reducing the risk of infection.
  • the present invention provides a class of compounds that can specifically target the novel coronavirus, and uses the compounds for product development.
  • the active ingredients of the compound are prepared from blackberry, red berry, blueberry, pomegranate and other fruit extracts or chemical synthesis.
  • the main ingredients include ellagic acid and ellagic acid derivatives (including but not limited to ellagic acid methylation products). , Ellagic acid structural modification and the like).
  • the active ingredients in the product were found in molecular interaction studies, which specifically bind to the surface immunogen (ligand) of the new coronavirus, and reduce the binding of the ligand to the receptor (ACE2) of the new coronavirus within the effective concentration range of the compound Response value:
  • the results of this study suggest that the active ingredients in the product can specifically weaken the infection ability of the new coronavirus, thereby preventing the infection of the new coronavirus and reducing the risk of human-to-human transmission.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Dermatology (AREA)
  • Virology (AREA)
  • Environmental Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Medicinal Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Agronomy & Crop Science (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Dentistry (AREA)
  • Molecular Biology (AREA)
  • Textile Engineering (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Birds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

Abstract

The present invention relates to the technical field of medicines, and relates to a compound for efficiently and specifically preventing and treating novel coronavirus infection and an application thereof. The effective component of the compound comprises ellagic acid and ellagic acid derivatives (comprising but are not limited to analogs such as ellagic acid methylation products and ellagic acid structural modifiers). The effective use concentration range of the compound is 10 ng/ml to 1000 ug/ml or 10 ng/g to 1000 ug/g. The compound is used for product development. The developed product is used for preventing and treating novel coronavirus infection, can specifically weaken the infection capability of novel coronavirus, thereby preventing and treating novel coronavirus infection and reducing the risk of human-to-human transmission.

Description

鞣花酸在防治新型冠状病毒感染中的应用Application of ellagic acid in the prevention and treatment of new coronavirus infection 技术领域Technical field

本发明属于医药技术领域，具体的说，涉及一类高效特异性防治新型冠状病毒感染的化合物及其应用。The present invention belongs to the field of medical technology, and in particular, relates to a class of compounds for highly effective and specific prevention and treatment of novel coronavirus infections and their applications.

背景技术Background technique

[根据细则9.2改正04.06.2020]　
[Corrected in accordance with Rule 9.2 04.06.2020]

新型冠状病毒肺炎，简称“新冠肺炎”，是一类急性传染性疾病，由2019新型冠状病毒(2019-nCoV)感染引起。人感染了新型冠状病毒以后，其主要症状包括呼吸道症状、发热、咳嗽、气促和呼吸困难等，在较严重病例中，感染可导致肺炎、严重急性呼吸综合征、肾衰竭，甚至死亡。目前针对新型冠状病毒引起的疾病，缺乏针对病原体的有效抗病毒药物，以隔离治疗、对症支持治疗为主。同时对广大易感人群，目前的防护产品如口罩、含酒精消毒用品等均为广谱式防护，市场上尚无高效、特异性阻隔病毒传染的防护用品。因此，利用现代科学技术，开发作用明确，具有高效、特异性防治新冠病毒感染的产品符合大众需求并具有极为重要的现实意义和社会意义。New type of coronavirus pneumonia, referred to as "new coronary pneumonia", is a type of acute infectious disease caused by the 2019 new type of coronavirus (2019-nCoV) infection. After a person is infected with the new coronavirus, the main symptoms include respiratory symptoms, fever, cough, shortness of breath, and difficulty breathing. In more severe cases, the infection can lead to pneumonia, severe acute respiratory syndrome, kidney failure, and even death. At present, there is a lack of effective antiviral drugs against pathogens for diseases caused by the new coronavirus, and isolation treatment and symptomatic and supportive treatment are the main ones. At the same time, for the majority of susceptible people, current protective products such as masks and alcohol-based disinfection products are broad-spectrum protection, and there is no high-efficiency and specific protection against virus infection on the market. Therefore, the use of modern science and technology, the development of products with clear functions, high-efficiency and specific prevention and treatment of new coronavirus infections meet the needs of the public and have extremely important practical and social significance.

发明内容Summary of the invention

基于现有防护用品只能进行广谱式防护，没有针对新型冠状病毒的高效、特异性防护产品的现状，本发明目的在于提供一类高效特异性防治病毒感染的化合物，特别是高效特异性防治新型冠状病毒感染的化合物，能够减弱新冠病毒的侵染能力，从而高效、特异性防治新冠病毒的感染，降低人传人风险。Based on the current situation that the existing protective equipment can only provide broad-spectrum protection, and there is no high-efficiency and specific protection product against the new coronavirus, the purpose of the present invention is to provide a class of compounds that can effectively and specifically prevent viral infections, especially high-efficiency and specific prevention and control. Compounds infected by the new coronavirus can weaken the infectivity of the new coronavirus, thereby efficiently and specifically preventing the infection of the new coronavirus and reducing the risk of human-to-human transmission.

为实现上述目的，本发明是通过如下技术方案实现的：In order to achieve the above objectives, the present invention is achieved through the following technical solutions:

所述的一类高效特异性防治病毒感染的化合物，该化合物主要成分包括鞣花酸、鞣花酸衍生物，其中鞣花酸衍生物包括但不限于鞣花酸甲基化产物、鞣花酸结构修饰物等类似物。Said compound for the prevention and treatment of virus infections with high efficiency and specificity. The main components of the compound include ellagic acid and ellagic acid derivatives. The ellagic acid derivatives include but are not limited to ellagic acid methylation products and ellagic acid. Structural modifications and the like.

进一步优选，所述的化合物由黑莓、红莓、蓝莓、石榴等水果中提取物或化学合成制备而成。More preferably, the compound is prepared from extracts from fruits such as blackberry, red berry, blueberry, pomegranate, etc. or chemically synthesized.

进一步优选，所述化合物有效使用浓度范围为1-1000ug/ml或1-1000ug/g。Further preferably, the effective concentration range of the compound is 1-1000ug/ml or 1-1000ug/g.

所述的化合物在制备具有防治新冠病毒感染作用的产品中的应用。The application of the compound in the preparation of a product with the effect of preventing and treating new coronavirus infection.

进一步优选，所述产品包括药物、医疗设备、保健品、消杀用品或防护用品；所述药物 或保健品的形式包括但不限于片剂、颗粒剂、硬胶囊、软胶囊、口服液、粉剂、合剂、丸剂、滴丸、喷雾剂、气雾剂、粉雾剂、滴眼液、牙膏、漱口水、面膜、护手霜；所述消杀用品包括但不限于肥皂、洗手液、消毒液、消毒凝胶、湿纸巾、洗衣液、口罩等。Further preferably, the product includes drugs, medical equipment, health products, disinfection products or protective products; the forms of the drugs or health products include, but are not limited to, tablets, granules, hard capsules, soft capsules, oral liquids, and powders. , Mixtures, pills, dripping pills, sprays, aerosols, powder mists, eye drops, toothpaste, mouthwashes, facial masks, hand creams; the disinfection products include but are not limited to soap, hand sanitizer, disinfectant , Disinfecting gel, wet tissues, laundry detergent, masks, etc.

本发明的有益效果：The beneficial effects of the present invention:

本发明提供一类能够特异性靶向新型冠状病毒的化合物，该化合物有效成分包括鞣花酸、鞣花酸衍生物(包括但不限于鞣花酸甲基化产物、鞣花酸结构修饰物等类似物)，有效使用浓度范围为10ng/ml至1000ug/ml或10ng/g至1000ug/g。利用该化合物进行产品开发，所开发产品用于防治新冠病毒的感染，可特异性减弱新冠病毒的侵染能力，从而防治新冠病毒的感染，降低人传人风险。The present invention provides a class of compounds that can specifically target the novel coronavirus. The effective ingredients of the compound include ellagic acid, ellagic acid derivatives (including but not limited to ellagic acid methylation products, ellagic acid structural modifications, etc.) Analogs), the effective use concentration range is 10ng/ml to 1000ug/ml or 10ng/g to 1000ug/g. The compound is used for product development, and the developed product is used to prevent and treat the infection of the new coronavirus, which can specifically weaken the infection ability of the new coronavirus, thereby preventing the infection of the new coronavirus and reducing the risk of human-to-human transmission.

具体实施方式Detailed ways

为了使本发明的目的、技术方案和有益效果更加清楚，下面将对本发明的优选实施例进行详细的说明，以方便技术人员理解。In order to make the objectives, technical solutions, and beneficial effects of the present invention clearer, the preferred embodiments of the present invention will be described in detail below to facilitate the understanding of the skilled person.

本发明为包含有一类具有高效特异性防治新冠病毒感染的化合物有效成分的药物、医疗器械、保健品或消杀用品等产品。The present invention is a medicine, medical device, health care product or disinfectant product containing a class of effective ingredients of a compound that has high efficiency and specificity to prevent and treat new coronavirus infections.

实例1Example 1

消毒凝胶中添加有效浓度范围内的鞣花酸，添加后的消毒凝胶在可以有效降低新冠病毒在皮肤表面的残留，进而降低感染风险。The disinfectant gel is added with ellagic acid within the effective concentration range, and the added disinfectant gel can effectively reduce the residue of the new coronavirus on the skin surface, thereby reducing the risk of infection.

实例2Example 2

口罩夹层中添加有效浓度范围内的鞣花酸，有效隔绝口罩外侧新冠病毒通过呼吸方式进入到呼吸系统。Ellagic acid in the effective concentration range is added to the interlayer of the mask to effectively isolate the new crown virus on the outside of the mask from entering the respiratory system through respiration.

实例3Example 3

护手霜中添加有效浓度范围内的化合物，添加后的护手霜涂抹在皮肤表面后，有效清除新冠病毒在手部的残留，有效清除皮肤表面的残留，进而降低感染风险。The hand cream is added with compounds within the effective concentration range. After the added hand cream is applied to the surface of the skin, it can effectively remove the residues of the new crown virus on the hands and effectively remove the residues on the skin surface, thereby reducing the risk of infection.

实例4Example 4

消毒液中添加有效浓度范围内的化合物，通过喷洒的方式释放到环境中，降低环境中新冠病毒的传染能力，减小感染风险。The disinfectant is added with compounds within the effective concentration range and released into the environment by spraying, reducing the infectious ability of the new coronavirus in the environment and reducing the risk of infection.

实例5Example 5

湿纸巾中添加有效浓度范围内的化合物，外出时通过擦拭手预防新冠病毒在手上的残留，减小感染风险。Add compounds within the effective concentration range to wet tissues, and wipe your hands when you go out to prevent the new coronavirus from remaining on your hands and reduce the risk of infection.

本发明提供一类能够特异性靶向新型冠状病毒的化合物，并利用该化合物进行产品开发。 该化合物的有效成分由黑莓、红莓、蓝莓、石榴等水果中提取物或化学合成制备而成，主要成分包括鞣花酸、鞣花酸衍生物(包括且不限于鞣花酸甲基化产物、鞣花酸结构修饰物等类似物)。The present invention provides a class of compounds that can specifically target the novel coronavirus, and uses the compounds for product development. The active ingredients of the compound are prepared from blackberry, red berry, blueberry, pomegranate and other fruit extracts or chemical synthesis. The main ingredients include ellagic acid and ellagic acid derivatives (including but not limited to ellagic acid methylation products). , Ellagic acid structural modification and the like).

产品中有效成分在分子互作研究中发现，其与新型冠状病毒表面免疫原(配体)特异性结合，且在该化合物有效浓度范围内降低配体与新冠病毒的受体(ACE2)的结合响应值；该研究结果提示产品中有效成分可特异性减弱新冠病毒的侵染能力，从而防治新冠病毒的感染，降低人传人风险。The active ingredients in the product were found in molecular interaction studies, which specifically bind to the surface immunogen (ligand) of the new coronavirus, and reduce the binding of the ligand to the receptor (ACE2) of the new coronavirus within the effective concentration range of the compound Response value: The results of this study suggest that the active ingredients in the product can specifically weaken the infection ability of the new coronavirus, thereby preventing the infection of the new coronavirus and reducing the risk of human-to-human transmission.

最后说明的是，以上优选实施例仅用于说明本发明的技术方案而非限制，尽管通过上述优选实施例已经对本发明进行了详细的描述，但本领域技术人员应当理解，可以在形式上和细节上对其作出各种各样的改变，而不偏离本发明权利要求书所限定的范围。Finally, it should be noted that the above preferred embodiments are only used to illustrate the technical solutions of the present invention and not to limit them. Although the present invention has been described in detail through the above preferred embodiments, those skilled in the art should understand that it can be combined in form and Various changes are made to the details without departing from the scope defined by the claims of the present invention.

Claims (5)

一类高效特异性防治病毒感染的化合物，其特征在于：所述化合物主要成分包括鞣花酸、鞣花酸衍生物，其中鞣花酸衍生物包括但不限于鞣花酸甲基化产物、鞣花酸结构修饰物等类似物。A class of compounds for the prevention and treatment of virus infections with high efficiency and specificity, characterized in that the main components of the compound include ellagic acid and ellagic acid derivatives, among which ellagic acid derivatives include but are not limited to ellagic acid methylation products, ellagic acid derivatives, and ellagic acid derivatives. Structural modification of anthuric acid and the like. 根据权利要求1所述的化合物，其特征在于：所述的化合物由黑莓、红莓、蓝莓、石榴等水果中提取物或化学合成制备而成。The compound according to claim 1, wherein the compound is prepared by extracting from fruits such as blackberry, red berry, blueberry, pomegranate, or chemical synthesis. 根据权利要求1所述的化合物，其特征在于：所述化合物有效使用浓度范围为1-1000ug/ml或1-1000ug/g。The compound according to claim 1, wherein the effective concentration range of the compound is 1-1000ug/ml or 1-1000ug/g. 权利要求1-3任一项所述的化合物在制备具有防治新冠病毒感染作用的产品中的应用。The use of the compound according to any one of claims 1 to 3 in the preparation of a product with the effect of preventing and treating neocoronavirus infection. 根据权利要求4所述的化合物在制备具有防治新冠病毒感染作用的产品中的应用，其特征在于：所述产品包括药物、医疗设备、保健品、消杀用品或防护用品；所述药物或保健品的形式包括但不限于片剂、颗粒剂、硬胶囊、软胶囊、口服液、粉剂、合剂、丸剂、滴丸、喷雾剂、气雾剂、粉雾剂、滴眼液、牙膏、漱口水、面膜、护手霜；所述消杀用品包括但不限于肥皂、洗手液、消毒液、消毒凝胶、湿纸巾、洗衣液、口罩。The application of the compound according to claim 4 in the preparation of a product with the effect of preventing and treating new coronavirus infection, characterized in that: the product includes drugs, medical equipment, health products, disinfection products or protective products; the drugs or health care products Product forms include but are not limited to tablets, granules, hard capsules, soft capsules, oral liquids, powders, mixtures, pills, drop pills, sprays, aerosols, powder mists, eye drops, toothpaste, mouthwashes , Facial mask, hand cream; the disinfection products include but are not limited to soap, hand sanitizer, disinfectant, disinfectant gel, wet tissue, laundry detergent, mask.
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