WO2021164401A1 - 一种中药组合物在制备治疗或预防冠状病毒感染的药物中的应用 - Google Patents

一种中药组合物在制备治疗或预防冠状病毒感染的药物中的应用 Download PDF

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WO2021164401A1
WO2021164401A1 PCT/CN2020/136903 CN2020136903W WO2021164401A1 WO 2021164401 A1 WO2021164401 A1 WO 2021164401A1 CN 2020136903 W CN2020136903 W CN 2020136903W WO 2021164401 A1 WO2021164401 A1 WO 2021164401A1
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parts
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chinese medicine
traditional chinese
medicine composition
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French (fr)
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肖伟
曹亮
王振中
章晨峰
张新庄
曹泽彧
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江苏康缘药业股份有限公司
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A61K36/282—Artemisia, e.g. wormwood or sagebrush
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/35—Caprifoliaceae (Honeysuckle family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/35—Caprifoliaceae (Honeysuckle family)
    • A61K36/355—Lonicera (honeysuckle)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/74—Rubiaceae (Madder family)
    • A61K36/744—Gardenia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/50—Methods involving additional extraction steps
    • A61K2236/51—Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying

Definitions

  • the invention relates to the field of disease treatment drugs, and more specifically, to the application of a traditional Chinese medicine composition in the preparation of drugs for the treatment or prevention of coronavirus infections.
  • 2019-nCoV is a new type of coronavirus belonging to the ⁇ genus. It has an envelope, and the particles are round or elliptical, often pleomorphic, with a diameter of 60-140nm. Its genetic characteristics are obviously different from SARSr-CoV and MERSr-CoV. Current research shows that the homology with bat SARS-like coronavirus (bat-SL-CoVZC45) is more than 85%. Droplet and close contact transmission are the main transmission routes, and there is a possibility of aerosol transmission when exposed to high concentrations of virus aerosols for a long time in a relatively closed environment.
  • Reduning injection is refined from the three traditional Chinese medicines of honeysuckle, gardenia and artemisia annua. It has the effects of clearing away heat, dispelling wind and detoxification. It is clinically mainly used to treat colds, coughs, upper respiratory tract infections, and acute symptoms caused by exogenous wind-heat. Bronchitis and other diseases, the curative effect is definite, the effect is remarkable. Whether it can effectively prevent and treat coronavirus-related diseases, especially COVID-19, urgently requires scientific research.
  • the present invention aims to propose an application of a Chinese medicine composition in the preparation of medicines for the treatment or prevention of coronavirus infections, wherein the Chinese medicine composition includes the following raw materials: 5-30 parts by weight of Artemisia annua, and 3 parts by weight of honeysuckle. 20 parts by weight, 2-15 parts by weight of gardenia.
  • coronavirus infection disease includes COVID-19.
  • the traditional Chinese medicine composition comprises the following raw materials by weight: 5-25 parts by weight of Artemisia annua, 3-15 parts by weight of honeysuckle, and 2-12 parts by weight of gardenia.
  • the traditional Chinese medicine composition comprises the following raw materials in parts by weight: 10-25 parts by weight of Artemisia annua, 6-15 parts by weight of honeysuckle, and 4-12 parts by weight of gardenia.
  • the traditional Chinese medicine composition includes the following raw materials in parts by weight: 20-25 parts by weight of Artemisia annua, 12-15 parts by weight of honeysuckle, and 10-12 parts by weight of gardenia.
  • the traditional Chinese medicine composition includes the following raw materials in parts by weight: 11 parts by weight of Artemisia annua, 8 parts by weight of honeysuckle, and 7 parts by weight of gardenia.
  • the traditional Chinese medicine composition includes the following raw materials in parts by weight: 15 parts by weight of Artemisia annua, 11 parts by weight of honeysuckle, and 10 parts by weight of gardenia.
  • the traditional Chinese medicine composition comprises the following raw materials in parts by weight: 25 parts by weight of Artemisia annua, 15 parts by weight of honeysuckle, and 12 parts by weight of gardenia.
  • the above-mentioned traditional Chinese medicine composition can be made into various pharmacological dosage forms by adding some pharmaceutically acceptable auxiliary materials, such as decoctions, granules, capsules, tablets, oral liquids, pills, tinctures, syrups, suppositories, suppositories, Gels, sprays, injections, etc.
  • the crude drug can be directly ground into powder, or it can be an extract prepared by conventional means in the field; the composition can be directly ground into powder by traditional methods, or it can be prepared by conventional means Extract.
  • the present invention also provides an optional preparation method of a traditional Chinese medicine composition for preventing or treating coronavirus infection, characterized in that the method comprises:
  • Honeysuckle and Artemisia annua L Combine the decoction liquid, concentrate and dry, to obtain honeysuckle and artemisia annua dry paste powder.
  • Gardenia jasminoides are crushed into coarse powder, heated to reflux with ethanol solution, filtered, the filtrate is recovered ethanol and concentrated, adjusted to acidity with hydrochloric acid, heated for 0.5-1.5 hours, refrigerated for 10-14 hours, filtered, the filtrate is concentrated, and dried to obtain gardenia Dry paste powder.
  • Take the volatile oil conventionally wrapped with auxiliary materials or directly take the volatile oil, and mix it with the above-mentioned dry paste powder.
  • directly or by adding pharmaceutically acceptable excipients to prepare a clinically acceptable dosage form.
  • the traditional Chinese medicine composition of the present invention can exhibit a good protective effect on VeroE6 cells infected with 2019-nCoV virus at a dilution concentration of 1:5000, 1:10000, and 1:20000 to the original solution of Reduning injection.
  • the latter cells do not undergo pathological changes, and can inhibit the replication of 2019-nCoV in cells, indicating that the traditional Chinese medicine composition of the present invention has a good effect of treating or preventing coronavirus-related diseases.
  • the present invention provides a use of a traditional Chinese medicine composition, and those skilled in the art can learn from the content of this article and appropriately improve the process parameters to achieve it.
  • all similar replacements and modifications are obvious to those skilled in the art, and they are all deemed to be included in the present invention.
  • the method and application of the present invention have been described through the preferred embodiments. It is obvious that relevant personnel can modify or appropriately change and combine the methods and applications herein without departing from the content, spirit and scope of the present invention to realize and apply the present invention.
  • Invent technology is obvious that relevant personnel can modify or appropriately change and combine the methods and applications herein without departing from the content, spirit and scope of the present invention to realize and apply the present invention.
  • the medicines, biological materials, or instruments used in the present invention are all common commercially available products, and all can be purchased in the market.
  • honeysuckle and artemisia annua are soaked in 13-18 times the amount of water for 3 hours, heated and decocted and distilled twice for 2 hours each time, and the volatile oil is collected at the same time, and set aside. Combine the decoction and concentrate under reduced pressure to a relative density of 1.03-1.08. Centrifuge at a high speed (20000 revolutions/min) to take the supernatant. After graded ultrafiltration, the ultrafiltrate is concentrated under reduced pressure to a relative density of 1.10-1.12 at 50°C. Dry, get honeysuckle, annua annua dry paste powder.
  • honeysuckle and artemisia annua are soaked in 13-18 times the amount of water for 3 hours, heated and decocted and distilled twice for 2 hours each time, and the volatile oil is collected at the same time, and set aside. Combine the decoction and concentrate under reduced pressure to a relative density of 1.03-1.08. Take the supernatant by high-speed centrifugation (20000 rpm) and concentrate under reduced pressure to a relative density of 1.10-1.12 at 50°C. Dry under vacuum to obtain honeysuckle and artemisia annua Dry paste powder.
  • Test drug the drug prepared in Example 1 of the present invention.
  • VeroE6 cells preserved by the Pathogen Center of the Institute of Medical Laboratory Animals, Chinese Academy of Medical Sciences.
  • 2019-nCoV virus The titer is 10 5 TCID 50 /ml, and it is stored at -80°C by the Pathogen Center of the Institute of Medical Laboratory Animals, Chinese Academy of Medical Sciences. Use virus titer 100TCID 50.
  • the drug group of the present invention is set at 3 concentrations, which can effectively inhibit the replication of 2019-nCoV on the cell. The results are shown in Table 1.
  • the samples prepared according to Example 1 of the present invention can inhibit the replication of 2019-nCoV in cells at 1:5000, 1:10000, and 1:20000 dilutions, suggesting that Reduning injection
  • the liquid has in vitro anti-2019-nCoV activity.

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Abstract

一种中药组合物在制备治疗或预防冠状病毒感染的药物中的应用，所述中药组合物由下述重量份比例的原料药制成：青蒿5～30重量份，金银花3～20重量份，栀子2～15重量份，该中药组合物在1:5000、1:10000、1:20000倍稀释浓度下，能够抑制2019-nCoV在VeroE6细胞内复制，使感染后的细胞不发生病变。

Description

一种中药组合物在制备治疗或预防冠状病毒感染的药物中的应用 技术领域
本发明涉及疾病治疗药物领域，更具体地说，涉及一种中药组合物在制备治疗或预防冠状病毒感染的药物中的应用。
背景技术
2019-nCoV属于β属的新型冠状病毒，有包膜，颗粒呈圆形或椭圆形，常为多形性，直径60-140nm。其基因特征与SARSr-CoV和MERSr-CoV有明显区别。目前研究显示与蝙蝠SARS样冠状病毒(bat-SL-CoVZC45)同源性达85％以上。飞沫和密切接触传播是主要的传播途径，在相对封闭的环境中长时间暴露于高浓度病毒气溶胶的情况下存在气溶胶传播的可能。患者以发热、乏力、干咳为主要表现，少数伴有鼻塞、流涕、腹泻等症状。重型病例多在一周后出现呼吸困难，严重者快速进展为急性呼吸窘迫综合征、脓毒症休克、难以纠正的代谢性酸中毒和出凝血功能障碍。
热毒宁注射液由金银花、栀子和青蒿三味中药精制而成，具有清热、疏风、解毒的功效，临床上主要用于治疗外感风热所致的感冒、咳嗽、上呼吸道感染、急性支气管炎等症，疗效确切、效果显著。其能否成为有效预防及治疗冠状病毒相关疾病特别是COVID-19亟待开展科学研究。
发明内容
有鉴于此，本发明旨提出一种中药组合物在制备治疗或预防冠状病毒感染的药物中的应用，其中，该中药组合物包括下述原料药：青蒿5～30重量份，金银花3～20重量份，栀子2～15重量份。
进一步地，所述冠状病毒感染疾病包括COVID-19。
优选的，所述中药组合物包括下述重量份原料药：青蒿5～25重量份，金银花3～15重量份，栀子2～12重量份。
更优选的，所述中药组合物包括下述重量份的原料药：青蒿10～25重量份，金银花6～15重量份，栀子4～12重量份。
更优选的，所述中药组合物包括下述重量份的原料药：青蒿20～25重量份，金银花12～15重量份，栀子10～12重量份。
更优选的，所述中药组合物包括下述重量份的原料药：青蒿11重量份，金银花8重量份，栀子7重量份。
更优选的，所述中药组合物包括下述重量份的原料药：青蒿15重量份，金银花11重量份，栀子10重量份。
更优选的，所述中药组合物包括下述重量份的原料药：青蒿25重量份，金银花15重量份，栀子12重量份。
上述中药组合物，可以加入一些药学可接受的辅料制成药剂学上的多种剂型，如汤剂、颗粒剂、胶囊剂、片剂、口服液、丸剂、酊剂、糖浆剂、栓剂、栓剂、凝胶剂、喷雾剂、注射液等。其中，原料药可以直接研磨成粉，也可以是经过本领域常规手段制得的提取物等；组合物可以按传统方法直接将几味组合物直接研磨成粉，也可以是经过常规手段制得提取物。
本发明还提供了用于预防或治疗冠状病毒感染的中药组合物一可选的的制备方法，其特征在于，该方法包括：
金银花、青蒿加水浸泡，加热煎煮蒸馏，收集挥发油，备用。合并煎煮液，浓缩干燥，得金银花、青蒿干膏粉。栀子粉碎成粗粉，用乙醇溶液加热回流，滤过，滤液回收乙醇并浓缩，用盐酸调成酸性，加热0.5-1.5小时，冷藏10-14小时，滤过，滤液浓缩，干燥，得栀子干膏粉。取挥发油经辅料经常规包裹后或直接取挥发油，与上述干膏粉混匀。最后经过常规工序直接或加入药学上可接受的赋型剂制成临床可接受的 剂型。
本发明的中药组合物在对热毒宁注射液原液1:5000，1:10000，1:20000倍稀释浓度下，能够在2019-nCoV病毒感染的VeroE6细胞上表现出良好的保护作用，使感染后的细胞不发生病变，可抑制2019-nCoV在细胞内复制，说明本发明的中药组合物具有良好的治疗或预防冠状病毒相关疾病的效果。
具体实施方式
本发明提供了一种中药组合物的用途，本领域技术人员可以借鉴本文内容，适当改进工艺参数实现。特别需要指出的是，所有类似的替换和改动对本领域技术人员来说是显而易见的，它们都被视为包括在本发明。本发明的方法及应用已经通过较佳实施例进行了描述，相关人员明显能在不脱离本发明内容、精神和范围内对本文的方法和应用进行改动或适当变更与组合，来实现和应用本发明技术。
除有特别说明，本发明采用的药品、生物材料或仪器皆为普通市售品，皆可于市场购得。
下面结合实施例，进一步阐述本发明：
实施例1
青蒿1250g 金银花750g 栀子600g
以上三味，金银花、青蒿加13-18倍量水浸泡3小时，加热煎煮蒸馏2次，每次2小时，同时收集挥发油，备用。合并煎煮液，减压浓缩至相对密度为1.03-1.08，高速离心(20000转/min)取上清液，分级超滤，超滤液减压浓缩至50℃相对密度为1.10-1.12，真空干燥，得金银花、青蒿干膏粉。栀子粉碎成粗粉，用6倍量80％乙醇加热回流1-3次，每次1小时，合并药液，滤过，滤液回收乙醇并浓缩至1∶1，用盐酸调pH4.0，100℃加热1小时，冷藏12小时，滤过，滤液浓缩至50℃相对密度为1.10-1.12，真空干燥，得栀子干膏粉。取挥发油，加入6g波洛沙姆108研磨混匀后，加入900ml注射用水中，搅拌使之澄明，再加入 上述干膏粉，搅拌使溶解，用氢氧化钠溶液调pH值为7.5-8.0，加注射用水至1000ml。用G4垂熔漏斗滤过，灌封于10ml安瓿中，100℃流通蒸汽灭菌。每支10ml，相当生药26克，静脉滴注，本品10-20ml注射液，加入5％葡萄液或0.9％氯化钠注射液250-500ml。
实施例2
青蒿1100g 金银花800g 栀子700g
以上三味，金银花、青蒿加13-18倍量水浸泡3小时，加热煎煮蒸馏2次，每次2小时，同时收集挥发油，备用。合并煎煮液，减压浓缩至相对密度为1.03-1.08，高速离心(20000转/min)取上清液，减压浓缩至50℃相对密度为1.10-1.12，真空干燥，得金银花、青蒿干膏粉。栀子粉碎成粗粉，用6倍量80％乙醇加热回流1-3次，每次1小时，合并药液，滤过，滤液回收乙醇并浓缩至1∶1，用盐酸调pH4.0，100℃加热1小时，冷藏12小时，滤过，滤液浓缩至50℃相对密度为1.10-1.12，真空干燥，得栀子干膏粉。取上述挥发油与干膏粉，加入0.5-1.5倍量的食用植物油，研磨，经常规工艺压制成软胶囊1000粒，即得组合物的软胶囊，每粒装0.55g，相当于原药材2.6g。
药效试验例
1.实验材料
受试药物：本发明实施例1制得的药物。
VeroE6细胞：由中国医学科学院医学实验动物研究所病原中心保存。
2019-nCoV病毒：滴度为10 5TCID 50/ml，由中国医学科学院医学实验动物研究所病原中心-80℃保存。使用病毒滴度为100TCID 50。
2.实验方法
无菌96孔培养板，每孔加入200μl浓度为5×10 4cell/ml Vero E6细胞，37℃ 5％CO 2培养24小时；受试药物稀释成3个浓度(1:5000，1:10000， 1:20000)，每个浓度5个复孔，每孔100μl，然后每孔再加入等体积100TCID50病毒，作用1h；1h后，弃去96孔培养板中细胞培养液，加入上述混合液；同时设立细胞对照、空白对照(溶剂对照)和病毒对照(阴性对照)；细胞37℃，5％CO 2孵箱孵育4-5天；光学显微镜下观察细胞病变(CPE)，细胞完全病变记录为“++++”，75％病变记录为“+++”，50％病变记录为“++”，25％病变记录为“+”，未病变记录为“－”。
3.实验条件：以上实验操作均在BSL-3实验室内完成。
4.结果判断：细胞不出现CPE为有效抑制病毒的浓度，出现CPE为无效。
5.实验结果：
本发明药物组设置3个浓度，在细胞上均能有效抑制2019-nCoV复制。结果见表1。
表1.药物抗2019-nCoV效果
Figure PCTCN2020136903-appb-000001
备注：“－”为未病变；“++++”为细胞完全病变。
6.结论：
根据细胞水平的筛选结果，根据本发明实施例1制得的样品在1:5000、1:10000、1:20000倍稀释浓度下，均可抑制2019-nCoV在细胞内复制，提示热毒宁注射液具有体外抗2019-nCoV活性。

Claims (10)

  1. 一种中药组合物在制备治疗或预防冠状病毒感染的药物中的应用，其特征在于所述中药组合物由下述重量份比例的原料药制成：青蒿5～30重量份，金银花3～20重量份，栀子2～15重量份。
  2. 根据权利要求1所述的应用，其特征在于所述冠状病毒感染包括COVID-19。
  3. 根据权利要求1所述的应用，其特征在于所述中药组合物包括下述重量份比例的原料药：青蒿5～25重量份，金银花3～15重量份，栀子2～12重量份。
  4. 根据权利要求1所述的应用，其特征在于所述中药组合物包括下述重量份比例的原料药：青蒿10～25重量份，金银花6～15重量份，栀子4～12重量份。
  5. 根据权利要求1所述的应用，其特征在于所述中药组合物包括下述重量份比例原料药：青蒿11重量份，金银花8重量份，栀子7重量份。
  6. 根据权利要求1所述的应用，其特征在于所述中药组合物包括下述重量份比例原料药：青蒿15重量份，金银花11重量份，栀子10重量份。
  7. 根据权利要求1所述的应用，其特征在于所述中药组合物包括下述重量份比例原料药：青蒿25重量份，金银花15重量份，栀子12重量份。
  8. 根据权利要求1-7任一所述的应用，其特征在于所述治疗或预 防冠状病毒感染的药物包括汤剂、颗粒剂、胶囊剂、片剂、口服液、丸剂、酊剂、糖浆剂、栓剂、凝胶剂、喷雾剂、注射剂。
  9. 根据权利要求1-7任一所述的应用，其特征在于所述中药组合物的制备方法包括以下步骤：
    步骤A:金银花、青蒿加水浸泡，加热煎煮蒸馏，收集挥发油，备用，合并煎煮液，浓缩干燥，得金银花、青蒿干膏粉；
    步骤B:栀子粉碎成粗粉，用乙醇溶液加热回流，滤过，滤液回收乙醇并浓缩，用盐酸调成酸性，加热0.5-1.5小时，冷藏10-14小时，滤过，滤液浓缩，干燥，得栀子干膏粉；
    步骤C:取挥发油经辅料经常规包裹后或取挥发油，与所述金银花、青蒿干膏粉以及所述栀子干膏粉混匀。
  10. 根据权利要求9所述的应用，其特征在于所述治疗或预防冠状病毒感染的药物包括口服给药剂型、注射给药剂型、雾化给药剂型或外用给药制剂。
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