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    An Overview on The Antiviral Traditional Chinese Medicines

    2020-12-31 11:10:24BAITiankai白天凱TIANJingYANBin
    關(guān)鍵詞:連花清射干麻杏石

    BAI Tian-kai (白天凱), TIAN Jing (田 靜), YAN Bin (閆 濱)

    1.School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China

    2.School of TCM, Shandong University of Traditional Chinese Medicine, Jinan250355, China

    ABSTRACT Traditional Chinese Medicine (TCM) owns a long history of fighting viral diseases.TCM has acumulated a large amount of clinical experiences to treat viral diseases.Inner Canon of the Yellow Emperor (Huangdi Neijing , 300 BC) mentioned: When the five epidemics arrive, they are all infected by the same disease, regardless of their size, and have similar symptoms.Treatise on Cold Pathogenic Diseases(Shanghan Lun, 220 AD) described the plague sweeping across the country and killed almost all people.And, numerous prescriptions in Treatise on Cold Pathogenic Diseases (Shanghan Lun) were used until today.Pestilence Theory (Wenyi Lun, 1642) written by Wu Youxing differed from Treatise on Cold Pathogenic Diseases in its analysis of the characteristics of epidemics and therapeutic methods.A large number of classical antiviral traditional Chinese medicines and recipes have been accumulated.On the ground of traditional Chinese medicine, modern scientific methods were used to screen out a large number of antiviral traditional Chinese medicines to find new antiviral contents or form new recipes.Despite the disputation around the researchers, TCM provided effective therapeutics in the fight against the Coronavirus Disease(2019 COVID-19) epidemic in China.It demonstrated the potential advantages of Chinese medicines as antiviral medicines with broad research value and prospects.

    KEYWORDS Antiviral medicines; Traditional Chinese medicine; Review

    A virus is an acellular form, composed of a nucleic acid molecule (DNA or RNA) and proteins,living on parasitic organisms between living and non-living organisms.It can infect almost all living organisms with cellular structures.It is highly contagious and pathogenic.In recent years, the frequent occurrence of viral diseases around the world has posed a serious threat to human society.Antiviral strategy has become a major scientific issue for human being.Virus has a strong variation feature.It is easy to induce drug resistance.The development of antiviral medicines and vaccines need huge investment and a long cycle means that human have few effective medicines available for clinical use in the face of viral infection.

    Recent years, due to unique character and theory system of traditional Chinese medicine in the medical profession, some traditional Chinese medicines displayed special clinical effect in the treatment of virus infectious diseases.In the numerous explorations, more and more scholars have turned their attention to traditional Chinese medicine to defeat the viral diseases.

    ANTIVIRAL HISTORY OF TRADITIONAL CHINESE MEDICINE

    There is no concept of "virus" in traditional Chinese medicine.However, viral diseases belong to the category of science of epidemic febrile disease from the clinical manifestations and etiological features of viral diseases.The antiviral history of TCM is also a history of epidemic diseases[1].In China, the history associated with the prevention and treatment of viral diseases goes back to the pre-Qin Period.The prevention and treatment of viral diseases by traditional Chinese medicine has long been discussed by ancient physicians.The"Huangdi Neijing" of the Qin and Han Dynasties emphasized the importance of "qi" in the human body."qi" is vital energy, that is, the so-called "when the vital qi is stored in the body, the pathogenic qi cannot invade"."Shang Han Lun" in the Eastern Han Dynasty recorded "Tai Yang disease syndrome causes fever and thirst, and those who do not hate cold are regarded as a febrile disease".In the Jin Dynasty, Ge Hong advocated the use of purgative poison and the compatibility ofRhubarb(Da Huang),Mirabilite(Mang Xiao),Ephedra(Ma Huang),Semen Armeniacae Amarum(Xing Ren),Radix Scutellariae(Huang Qin),Radix Glycyrrhizae Preparata(Gan Cao) andCroton Tiglium(Ba Dou)as pills in his Book "Handbook of Prescriptions for Emergencies".He pointed out that "if the family members visit the sick, they can take the pills for profit first, then they will not become infected easily".There are several epidemic prevention prescriptions in Tang Dynasty Sun Simiao's "Essential Formulas for Emergencies" (Bei Ji Qian Jin Yao Fang).For example, "Realgar(Xiong Huang) andOrpiment(Ci Huang) are used as the main medicines, put it into a bag and wear the bag on the body and hang one on the door".Vaccination to prevent infectious diseases was put into practice in Song Dynasty.According to "Compendium of Materia Medica", white buffalo lice was used to prevent smallpox, and garlic was eaten to prevent diarrhea and cholerathe in Ming and Qing Dynasties.From a large number of ancient documents, it can be confirmed that ancient doctors accumulated a lot of clinical experience in the treatment of viral diseases.On the basis of these antiviral experiences, the science of epidemic febrile disease with antiviral as the core was gradually perfected in the long history and it developed maturely in the Qing Dynasty[2].

    RESEARCH ON THE SCIENCE OF EPIDEMIC FEBRILE DISEASE IN THE FIGHT AGAINST VIRUSES.

    In Chinese medicine, a large number of viral diseases are included in the science of epidemic febrile disease.If you are familiar with the definition of epidemic febrile disease, you will be able to determine whether certain viral diseases belong to the epidemic febrile disease.It is a kind of polar extrinsic fever caused by "evil warmth", which is regards as viral infection.The epidemic febrile disease can be divided into hyperthermia, dampheat, warm-pathogenic, pestilence and other types[3].It is characterized by "heat phase" predilection,easy dryness and injury to yin, infectious, epidemic,seasonal and regional.The treatment of these viral diseases is identified under the guidance of science of epidemic febrile disease, with clarifying the causes and mechanisms of the disease.The doctors chose the appropriate medicines and recipes to eliminate the evil and adjust the body status.Viral diseases are mainly treated by examining the cause of the disease, clearly identifying the mechanism of the disease, judging the evil and the good, and combining the symptoms.

    Depending on the cause of the viral disease and the stage of the disease, the following treatments are common[4-6].

    Release the body's energy and penetrate the surface: opening and releasing the tissue between the skin and the flesh, relieving surface evils.It is suitable for those who suffer from viral diseases at the beginning and whose evil spirits are in the surface of the body.Modern research on this method of prescription medicine has the effect of promoting sweat gland secretion, accelerating body heat dissipation and enhancing human immunity.

    Clearing Qi-Heat: Clearing heat and retaining fluids, quenching thirst and removing boredom.It is suitable for viral diseases with excessive heat in the qi, but not yet with dryness, food stagnation, phlegm and dampness and other Decoctionible evils.The modern study of the method of prescription has the effect of killing pathogenic microorganisms, antiinflammatory, enhance blood leukocyte phagocytosis.

    Expelling evil spirits: promoting the release of heat from the internal organs, promoting the release of stasis and breaking knots, etc.Modern research on this method has the effect of killing pathogenic microorganisms, anti-inflammatory and enhancing the phagocytosis of leukocytes in the blood.Modern research on this method of prescription has the effect of enhancing intestinal and stomach peristalsis, improving blood circulation in the intestines, antibacterial and anti-inflammatory.

    Harmonizing and dispelling of evil: resolving evil heat, relieving drains and subduing.Modern research on the method of the prescription has the role of antipyretic, antibacterial and antiinflammatory, cholestatic and adjust the function of the stomach and intestines.

    Eliminate dampness and clear heat: to promote the circulation of qi, transport the spleen and stomach, and clear the waterways.Modern research on this method of prescription has anti-infection,adjusting the function of the stomach and intestines.

    Open the aperture and awaken the spirit method: clearing the heart and purse evil heat,clearing damp heat and phlegm, etc.Modern research on this method of prescription has the role of anti-infection, adjusting the functions of the stomach and intestines.Modern research on this method of prescription has the effect of resolving heat and sedation, strengthening the heart.

    Nourishing Yin and generating fluids: nourishing yin fluid, dryness and fire, etc.Modern research on this method of prescription has the effect of inhibiting pathogenic microorganisms, neutralizing toxins,adjusting blood pressure, and so on.

    CLASSICAL CHINESE MEDICINES AND RECIPES COMMONLY USED FOR ANTIVIRAL IN ANCIENT AND MODERN TIME

    Chinese medicine has made great achievements in the fight against infectious diseases.In the long battle against viruses, due to the lack of modern chemical synthesis techniques, TCM has only been able to obtain antiviral medicines from natural resources.These medicines were derived from plants, animals and minerals.According to the characteristics of natural medicines, combined with the Chinese medical theory, these natural medicines are classified into traditional Chinese medicines with different functions .

    Classical Antiviral Traditional Chinese Medicines

    Antiviral traditional Chinese medicines is often not targeted at which kind of virus, but has a wide range of antiviral effect.Even these traditional Chinese medicines also have anti-inflammatory and antiseptic effects.For example, traditional Chinese medicines are able to inhibit many viruses such asFoliumo Isatidis(Da Qing Ye 大青葉) ,Radix Isatidis(Ban Lan Gen 板藍(lán)根),Belamcanda Chinensis(She Gan 射干),Lonicera Maackii(Jin Yin Hua 金銀花),Fructus Arctll(Niu Bang Zi 牛蒡子), etc.some of the classical anti-viral traditional Chinese medicinemedicines are listed in the following table[7-11].

    Classical Antiviral Traditional Chinese Medicine Recipes MEDICINES

    In the clinical practice of TCM, TCM practitioners often use a combination of traditional Chinese medicines to fight viral infections.Adhere to the guidance of the basic theories of TCM, a large number of classical anti-viral recipes, such as Yinqiao Powder (銀翹散), Qiaohe Decoction (翹荷湯), Zhuyeshigao Decoction (竹葉石膏湯).At the same time, these recipes have become the basis of the formula study.In clinical diagnosis and treatment, according to these classical recipes and their therapeutic experience, TCM practitioners add or subtract certain medicines so that recipes are better suited to the patient, resulting in faster and better treatment.These recipes not only fight viral infections, but also often have other effects, such as Sangju Drink (桑菊飲) which can treat children's urinary leakage and chronic conjunctivitis, acne,etc.The following classical recipes are commonly used[12-24].

    MODERN RESEARCH ON ANTI-VIRAL TRADITIONAL CHINESE MEDICINEMEDICINES AND RECIPES

    With the development of modern science and technology, based on the good efficacy of TCM in antiviral treatment, focusing on TCM, using advanced extraction, separation and identification technologies, researchers in inland and abroad were used to conduct antiviral research.At present, some highly effective anti-viral medicines have been selected from traditional Chinese medicinemedicines, which were widely used in the clinical treatment of various viral diseases.Most of the antiviral Chinese medicines screened are heat-clearing and detoxification medicines.The comparison table is as follows[25-36].

    At the same time, on the basis of the single drug research, some new recipes were formed.Forexample, Sanhuang Liquid (三黃液), which is composed of equal amounts ofRhizoma Coptidis(Huang Lian 黃連)Radix Scutellariae(Huang Qin 黃芩) andCortex Phellodendri(Huang Bai 黃柏), alcoholic extract, had the function of clearing heat and detoxifying and drying dampness and it had a positive effect on influenza virus, type I parainfluenza virus, adenovirus, herpes simplex virus, coxsackievirus B3, vesicular stomatitis virus,Newcastle disease virus, HIV.The antiviral and antibacterial recipes, made fromRadix Arnebiae(Zi Cao 紫草) andHerba Violae(Zi Hua Di Ding 紫花地丁), have anti-influenza virus, herpes simplex virus,vesicular stomatitis virus, and Newcastle disease virus and other activities.

    Relieving Exterior Syndromes Recipes:Xiaoqinglong Decoction (小青龍湯) , Daqinglong Decoction (大青龍湯), Sheganmahuang Decoction (射干麻黃湯), Yinqiao Powder (銀翹散), Sangju Drink (桑菊飲)Maxingshigan Decoction(麻杏石甘湯), Yinqiaomabo Powder (銀翹馬勃散),Gegen Decoction (葛根湯),Zhengchaihu Drink (正柴胡飲), Guizhi Decoction (桂枝湯) Xinjia Xiangru Drink (新加香薷飲), Jingfangbaidu Powder (荊防敗毒散) ,Yuebi Decoction (越婢湯), Lanyin Decoction (藍(lán)飲湯), Shenshu Powder (神術(shù)散)Heat-Clearing Recipes:Zhuyeshigao Decoction (竹葉石膏湯), Baihu Decoction (白虎湯), Baihurenshen Decoction (白虎人參湯), Baihucangzhu Decoction(白虎加蒼術(shù)湯) Qingying Decoction(清營湯), Xijiao Dihuang Decoction (犀角地黃湯), Pujixiaodu Drink (普濟(jì)消毒飲), Huanglianjiedu Decoction (黃連解毒湯) Qingwenbaidu Drink (清瘟敗毒飲), Biyu Powder(碧玉散), Liangge Powder (涼膈散), Qinggong Powder (清宮湯),Qiaohe Decoction(翹荷湯), Shengjiang Powder (升降散), Tongshengxiaodu Powder (通圣消毒散), Shaoyao Dihuang Decoction (芍藥地黃湯), Zhizichi Decoction (梔子豉湯)Anti-dampness Recipes Huopuxialing Decoction (藿樸夏苓湯), Sanren Decoction (三仁湯), Dayuan Drink (達(dá)原飲), Huanglian suye Decoction (黃連蘇葉湯),Ganluxiaodu Pills (甘露消毒丹)Yiyizhuye Powder (薏苡竹葉散), Wuling Powder (五苓散), Pingwei Powder (平胃散), Huoxiangzhengqi Powder (藿香正氣散),Maxingyigan Decoction (麻杏苡甘湯)Resuscitative Recipes: Angongniuhuang Pills (安宮牛黃丸), Zixue (紫雪)Harmonizing Recipes: Haoqinqingdan Decoction (蒿芩清膽湯), Xiaochaihu Decoction (小柴胡湯)Wind-curing Recipes: Lingjiaogouteng Decoction (羚角鉤藤湯)Tonic Recipes: Yupingfeng Powder (玉屏風(fēng)散)Dryness-moistening Recipes: Sangxing Decoction (桑杏湯)

    NOVEL ANTI-VIRAL CHINESE PATENT MEDICINES

    Chinese patent medicinemedicines are made from Chinese herbmedicines, based on the guidance of Chinese medicine theory, according to prescriptions and standards.Chinese patent medicines arein certain dosage forms.It can be used directly in the prevention and treatment of diseases.In recent decades, pharmaceutical workers in China have used modern preparation techniques to develop a series of Chinese patent medicines that can be used for the prevention and treatment of diseases.Anti-viral and antiinflammatory medicines such as Lianhuaqingwen Capsules (連花清瘟膠囊), Qingwenjiedu Tablet(清瘟解毒片), Shuanghuanglian Oral Liquid (雙黃連口服液), Banlangen Granules (板藍(lán)根顆粒),Jiuweiqianghuo Pills (九味羌活丸), Guizhi Mixture Liquid (桂枝合劑), Zheng Chaihu Granules (正柴胡飲顆粒), Qingkailing Injection (清開靈注射液), etc.Chinese patent medicinemedicines play a huge role in the clinical treatments[37,38].

    THE IMPORTANT ROLE AND LIMITATIONS OF TRADITIONAL CHINESE MEDICINEMEDICINES IN THE FIGHT AGAINST COVID-19

    Since December 2019, the new forms of coronavirus, Coronavirus Disease 2019(COVID-19)) have emerged around the world.The Chinese government has taken effective measures to bring the epidemic under control in China.COVID-19 is an acute respiratory infectious disease, classified as a category B level infectious disease under the Law of the People's Republic of China on the Prevention and Control of Infectious Diseases.It is managed according to category A level infectious diseases.

    A "√" in the table indicates that the drug is effective against the virus, while a blank indicates that it is not effective.

    The novel coronavirus belongs to the coronavirus subgenus Sarbe virus subgenus beta of the Coronaviridae family, enveloped.The particles are round or oval, often polymorphic,60-140 nm in diameter.Novel coronavirus and severe acute respiratory The SARS coronavirus(SARS-CoV) and the Middle East Respiratory Syndrome virus (MERS-CoV) are both SARSCoVs.Coronaviruses with a similar structure.The novel coronavirus consists of spike glycoprotein(S), hemagglutinin acetyl esterase (HACE), and the hemagglutinin acetyl esterase (HAE).Granulins,membrane glycoproteins, small molecules of membrane-bound glycoproteins, glyco-shell phosphoproteins, and ribonucleic acid make up the enzyme.Angiotensin-converting enzyme 2 (ACE2)The S protein plays a key role in recognizing and binding host cell surface receptors and mediating the interaction between the viral envelope and the cell membrane.S proteins may infect the human respiratory tract epithelial cells by binding to human ACE2 proteins.After the neo-coronavirus invades the cell, the envelope fuses with the cell membrane, releasing the viral genetic material RNA and synthesizing more RNA inside the cell and viral protein structures to form new coronavirus particles, which are secreted outside the cells by the Golgi apparatus and infect new cells.The virus rapidly spreads to organs, bronchi, and eventually to the alveoli, leading to pneumonia.The clinical manifestations are fever, cough, shortness of breath and decreased oxygen saturation.Grind glass-like shadow, severe cases develop into acute respiratory distress syndrome.A large number of viruses enter the body at the same time, activating the immune response, T cells and macrophages secrete interleukin-6 (IL-6), et al.A large number of inflammatory factors and an excessive immune response to cytokines produce a systemic inflammatory response syndrome, or inflammation.Factor storms, in severe cases, cause multiple organ failure and death[39].

    TCM Syndrome Differentiation and Treatment of COVID-19

    In the process of defeating Covid-19 in China,Traditional Chinese Medicine and medicines had played a pivotal role.According to Chinese medicine, Covid-19 belongs to the category of epidemic diseases, which are located in the lungs and are basically characterized by "dampness, heat,toxicity and stasis".The basic characteristics of the disease are "dampness, heat, toxicity and stasis".The external factor is that the human body feels the evil of the epidemic, while the internal factor is that the human body does not have enough positive energy.

    The National Administration of Traditional Chinese Medicine issued the "Treatment protocol for novel coronavirus pneumonia" ( COVID-19,seventh edition, on a trial basis)provided the patients who stayed observation, confirmed cases of mild, normal, heavy, critical and recovering with traditional Chinese medicines treatment plan.The period of medical observation was often characterized by weakness with gastrointestinal discomfort or fever.For fatigue with gastrointestinal discomfort, Chinese patent medicine medicinesHuoxiang Zhengqi Capsul (藿香正氣膠囊) is recommended.For fatigue with fever, Jinhua Qinggan Granules (金花清感顆粒),Lianhua Qingwen Capsule 蓮花清瘟膠囊, Shufeng Jedu Capsule (疏風(fēng)解毒膠囊) were recommended.The mild type of diagnosed cases was classified according to the identification of symptoms into cold and damp depression of the lungs and dampheat obstruction of the lungs.The common type was classified as dampness and toxin depression of the lungs, cold and dampness obstructing the lungs.The severe type was classified as epidemic toxin closure of the lungs and burnt the lungs.The critical type is characterized by internal closure and external detachment.Recovery is divided into lung-spleen-qi deficiency syndrome and qi-yin two deficiency syndrome.In the treatment of diagnosed cases, we get these Chinese medicines as followed to make up recipes.Herba Ephedrae(Ma Huang 麻黃),Fructus Tsaoko(Cao Guo草果),Radix Astragali(Huang Qi 黃芪),Rhizoma Pinelliae Preparatum(Fa Ban Xia 法半夏),Radix Scrophulariae(Xuan Shen 玄參),Rhizoma Anemarrhenae(Zhi Mu知母),Rhinocerotidae(Xi Niu Jiao犀牛角),Radix Paeoniae Rubrra(Chi Shao 赤芍),Rhizoma Atractylodis(Bai Zhu 白術(shù)),Folium Isatidis(Da Qing Ye 大青葉),Rhizoma Phragmitis(Lu Gen 蘆根),Rhizoma Polygoni Cuspidati(Hu Zhang 虎杖),Semen Coicis(Yi Yi Ren 薏苡仁),Exocarpium Citri Grandis(hua ju hong 化橘紅),Semen Lepidii(ting li zi 葶藶子),Rhizome Pinelliae preparata(Jiang Ban Xia 姜半夏),Cynanchum paniculatum(Bunge)Kitagawa(Xu Chang Qing 徐長卿),Medicated Leaven(Shen Qu神曲),Radix Glycyrrhizae Preparata(Zhi Gan Cao炙甘草),Wolfiporia cocos(Fu Ling 茯苓),Verbena officinalis L(Ma Bian Cao 馬鞭草),Rhizoma Zingiberis(Gan Jiang 干姜),Semen Armeniacae Amarum(Ku Xing Ren 苦杏仁), Cortex Magnoliae Officianalis(Hou Pu 厚樸),Gypsum Fibrosum(Shi Gao 石膏),Alisma plantago-aquatica Linn.(Ze Xie 澤瀉),Polyporus(Zhu Ling 豬苓),Rhizoma Atractylodis lmacrocephalae(Cang Zhu 蒼術(shù)),Radix Scutellariae(Huang Qin 黃芩),Radix Asteris(Zi Wan 紫菀),Rhizoma Belamcandae(She Gan 射干),Herba Asari(Xi Xin 辛夷),Rhizoma Dioscoreae(Shan Yao山藥),Fructus Aurantii Immaturus(Zhi Shi 枳實(shí)),Rhizoma Et Radix Notopterygii(Qiang Huo 羌活),Pheretima(Di Long 地龍),Herba Eupatorii(Pen Lan 佩蘭),Semen Arecae(Bing Lang 檳榔),Fructus Forsythiae(Lian Qiao 連翹),Herba Pogostemonis(Guang Huo Xiang 廣藿香),HerbaLophatheri(Dan Zhu Ye 淡竹葉),Radix Rehmanniae(Di Huang 地黃).Most of these traditional Chinese medicines have antiviral activity in modern research.For heavy and critical types,a combination of patent medicine injections and recipes was used.Such as XuebijingInjection(血必凈注射液), Xingnaojing Injection(醒腦靜注射液), Reduning Injection(熱毒寧注射液), Tanreqing Injection(痰熱清注射液), and Shenfu Injection(參附注射液),Shengmai Injection(生脈注射液), Shenmai Injection(參麥注射液)[40].

    Among these formulations[41], "Tripartite Three Medicines" is prominent.The "Tripartite Three Medicines" includes three proprietary Chinese patent medicines and three Chinese medicines formulas.Three proprietary Chinese patent medicines: Jinhuaqinggan Granules (金花清感顆粒), Lianhuaqingwen Capsule (連花清瘟膠囊), and xuebijing Injection (血必凈注射液).Three Chinese medicines formulas: Qingfeipaidu Decoction(清肺排毒湯), Xuanfeibaidu Prescription (宣肺排毒方), and Huashibaidu Prescription (化濕敗毒方).Clinical data disclosed by the relevant departments and regions show that the combination of Chinese and Western medicine has been effective in treating neo-coronary pneumonia, and patients' cure rates were positively correlated with TCM treatment participation rates.The intervention of Chinese medicine treatment is an important way to improve the cure rate and reduce mortality[42].The average time of stay in hospital has been significantly reduced by combining Chinese and Western medical treatment.

    The Extensive Application, Multi-center Clinical Evaluation and Safety Analysis of Qingfeipaidu Decotion (清肺排毒湯)

    After clinical treatment and observation, it was confirmed that the use of Qingfeipaidu Decoction in combination of traditional Chinese and western medicine, had a good clinical effect in the treatment of Covid-19, with a total effective rate of more than 90%.Qingfeipaidu Decoction (清肺排毒湯) is composed of Maxing Shigan Decoction (麻杏石甘湯), Shegan Mahuang Decoction (射干麻黃湯), Xiao Chaihu Decoction (小柴胡湯), and Wuling Powder(五苓散).

    Qingfeipaidu Decoction (清肺排毒湯)is the largest prescription in Wuhan City, Hubei Province,and no serious adverse reactions have been reported.so it had good clinical safety.In the main battlefield of anti-epidemic in Wuhan, " Qingfeipaidu Decoction (清肺排毒湯)" had been promoted in an all-round way and played a positive role.Since February 5, the Wuhan municipal government had distributed 380000 bags of " Qingfeipaidu Decoction(清肺排毒湯) " to designated hospitals, Fangcang hospitals and isolation points.A number of traditional Chinese medicines enterprises have provided nearly 100000 doses of recipe granules to Wuhan Fangcang Hospital free of charge.Hubei Provincial Health Commission trusted local traditional Chinese medicine enterprises to prepare and distribute nearly 500000 doses of recipe granules.It was used in designated hospitals in Hubei Province.The extensive use of Qingfeipaidu Decoction (清肺排毒湯) in Hubei and Wuhan showed good effects in the treatment of mild, common and suspected patients.And no serious adverse reactions have been reported.

    Under the lead of the State Administration of traditional Chinese Medicine, with the cooperation of provincial and municipal Chinese medicine administrations, coordinate 66 hospitals from 10 provinces and cities across the country to participate in integrated research and carry out multicenter clinical research.An expert group of Qingfeipaidu Decoction (清肺排毒湯) was established to guide the design of medical treatment and clinical research programs.

    A total of 878 patients with complete information submitted by 66 implementing units in 10 provinces were analyzed.The most common cases were 704 cases, accounting for 80.2%;11.3% of mild cases (99 878); 6.6% of severe cases (58vs 878) and 1.9% of severe cases (17 vs 878).It evaluated from the following aspects.The nucleic acid negative conversion average days of the Qingfeipaidu Decoction (清肺排毒湯) treatment team (multi-center) is 8.65 days.It is 3.15 days less than the Western medicine team.The average time of stay hospital is 14.4 days.It is 3.81days less than the Western medicine team.Chest imaging showed no abnormalities in the lungs in 10.9% (86/786) of patients prior to treatment,89.1% (700/ 786) patients presented with varying degrees of pulmonary lesions.After treatment 87.4% (626/716) of patients had varying degrees of lung lesion uptake 12.0% (86/716) of patients had no change in lung lesions before or after treatment(none were abnormal) 0.6% (4/716) The patient's lung foci showed increased exacerbations.Before the treatment of Qingfeipaidu Decoction (清肺排毒湯), 44.2% of patients with fever (temperature 37.3℃) were febrile.91% of fever patients will have temperatures in the normal range after 6 days of treatment with Qingfeipaidu Decoction (清肺排毒湯).Before treatment, 46.8% of patients had a cough, of which 54.0% showed a dry cough.28.0%fatigue, 11.3% shortness of breath.11.2% anorexia,10.3% sore throat.After 6 days of treatment with Lung Clearing and Detoxifying Soup, 92% of patients' asthma symptoms disappeared 65% of patients' fatigue symptoms disappeared 56% of patients' sore throat.Symptoms disappeared in 54% of patients with anorexia in 51% of patients with cough in 47% of patients with dry cough.878 patients referral Qingfeipaidu Decoction (清肺排毒湯) treatment team) in the multicenter 874 (99.5%)were discharged healed.4 cases (0.5%) of death.4 cases of death, all critical type, mean age 70.5 years, all with comorbidities.

    Safety analysis: 1.Adverse events.A total of 34 (3.75%) adverse event statistics were included in this study.There were a total of 0.55% and 5 times adverse responders.There were no serious adverse events in this study.Due to the high number of patients combining medications, it is not possible to state that the adverse reactions were related to Qingfeipaidu Decoction (清肺排毒湯).2.Aristolochic acid content assay.The content of AAI in Qingfeipaidu Decoction (清肺排毒湯) was even lower (0.000025%), which was only available to the public according to the Chinese Pharmacopoeia.About 17% of the test solution and about 50% of the decoction of fine spices.For the Qingfeipaidu Decoction (清肺排毒湯), the maximum daily intake of AAI for patients is only 1.5μg, which is much lower than the maximum daily intake of AAI in the Chinese Pharmacopoeia.The limit standard for AAI in pungent is 1/20.

    The Deficiency of Traditional Chinese Medicines in Antiviral Treatments MEDICINES

    The traditional Chinese medicinemedicines used in the fight against Covid-19 had a evident clinical effect, but there were still some problems which were also long-standing problems in the field of traditional Chinese medicine research.These problems were manifested as unclear targets of complex pharmacodynamic substances of traditional Chinese medicines, unclear mechanism,extensive pharmaceutical technology, backward quality control techniques, lax experimental design and so on.In order to solve these problems, we should continue to carry out the material basis research on the traditional Chinese medicinemedicines and traditional Chinese formula, and select the optimal recipe composition by adopting high-throughput screening method and application feedback system control (FSC).The structure of the active components, their targets of action and compatibility mechanism will be studied by using the technology of cell thermal transfer(CETSA), drug affinity response target stability(DARTS) combined with the analytical technology of mass spectrum(MS) and nuclear magnetic resonance(NMR).At the same time, we also need more stringent clinical experimental design to demonstrate the scientific connotation of theory of traditional Chinese medicinemedicines and relative recipes.

    PROSPECT OF ANTIVIRAL DEVELOPMENT OF TRADITIONAL CHINESE MEDICINEMEDICINES

    The traditional Chinese medicine (TCM)made great achievements in the treatment of viral diseases.Medicines have their duality of curative effects and toxic effects.To use their curative effects and avoid their toxic side-effects are the basic principle for traditional Chinese medicines recipe.Traditional Chinese recipes have a long history in the prevention and treatment of viral diseases.This antiviral history has accumulated a wealth of experience.Relying on rich resources of traditional Chinese medicinemedicines and unique theories of traditional Chinese medicine in China, the study of antiviral of traditional Chinese medicines has a broad prospect.There is an independent scientific system and research system for TCM.In terms of antiviral therapy of traditional Chinese medicines, the study of traditional Chinese medicines should adhere to the guidance of the theory of traditional Chinese medicine and construct multi-discipline, high-level and multidimensional high-throughput efficacy screening and evaluation system, so as to screen out more antiviral active ingredients and formulations of traditional Chinese medicines.

    On the basis of specific the structure of active components in antiviral traditional Chinese medicine, the active domain was modified so as to achieve stronger antiviral effect and establish a foundation for the development of new antiviral chemical medicines.We should be guided by the clinical curative effect, using advanced cell and molecular techniques so as to clear targets and mechanisms of traditional Chinese medicines effect.To achieve development of traditional Chinese medicine, we should use advanced technologies and means such as artificial intelligence, hadoop,chemical biology.In this epidemic outbreak, the clinical effect of Qingfeipaidu Decoction (清肺排毒湯) was evaluated and the hadoop technology on the Internet was used for collection and analysis,with the characteristics of rapid response, accurate evaluation and saving manpower and material resources.In the development of traditional Chinese medicines, we need to be open-minded and absorb the latest science and technology,so as to protect human health and make greater progress.

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