A compound traditional Chinese medicine composition for anti-virus and its application

Abstract

The present invention discloses a compound antiviral Chinese medicine composition, comprising the following raw materials: Artemisia annua, Scutellaria baicalensis, Forsythia suspensa, Talcum, Artemisia capillaris, Acorus calamus, Cardamom, Gypsum, Lepidium tiliaceum, Perilla frutescens, Pinellia ternata, and Scorched Liushenqu. Also disclosed are an antiviral Chinese medicine compound preparation prepared from the compound antiviral Chinese medicine composition, and the use of the compound antiviral Chinese medicine composition or the antiviral Chinese medicine compound preparation in the preparation of a drug for preventing or treating viral infection. The Chinese medicine compound preparation provided by the present invention can intervene in the middle stage of the clinical treatment of novel coronavirus infection, block the course of the disease; significantly alleviate symptoms; shorten the duration of fever and hospitalization; promote the absorption of inflammation and reduce sequelae; and reduce complications and toxic side effects of Western medicine. After receiving combined treatment of Chinese and Western medicine, patients receiving hospital treatment showed significant symptom improvement, fewer severe patients, and a good prognosis. The compound Chinese medicine composition of the present invention has great application potential in the treatment of the early stage of virus-related pneumonia.

Description

Technical Field

[0001] The present invention belongs to the field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition with antiviral effects, capable of preventing the onset of viral diseases, especially preventing respiratory infections mainly caused by viruses, and its medical uses. Background Art

[0002] Diseases caused by viruses are characterized by strong infectivity, wide prevalence, high mortality, etc. With the formation of world integration, the spread of viruses is more rapid and the impact is more extensive. Therefore, preventing viral diseases is a worldwide problem and a major national need. Among them, respiratory virus infections are the most common and most influential type of viral diseases clinically. Respiratory virus infections generally include common colds, influenza, and viral pharyngitis, etc., and are mainly transmitted through the air or hand contact via the nasal cavity. Approximately 10-20% of people worldwide are infected with influenza virus every year.

[0003] At present, there are many limitations in the prevention and treatment of respiratory viral diseases, especially for influenza viruses. The prevention and treatment of influenza viruses mainly focus on the research and application of antiviral drugs and specific vaccines. However, currently, anti-influenza drugs represented by oseltamivir and zanamivir have many problems such as treatment limitations, drug resistance, and adverse reactions. Vaccines only have a defensive effect against currently prevalent virus types and have no preventive effect on mutated viruses. Traditional Chinese medicine has once again demonstrated its unique role and curative effect in the treatment and prevention of respiratory virus infections, especially in the prevention and treatment of SARS, H1N1, novel coronavirus, etc., and has achieved good clinical effects. The advantage of traditional Chinese medicine is macroscopic overall dialectical treatment, which pays more attention to improving the physiological state of the body damaged and interfered by viruses, improving the overall quality of life of patients, enhancing the body's resistance, regulating the body's physiological state, forming an internal environment that is not conducive to virus replication, and even achieving a physiological and pathological state of harmonious coexistence between the body and the virus. Therefore, traditional Chinese medicine is expected to become an effective way to deal with respiratory virus infections. Summary of the Invention

[0004] The objective of the present invention is to provide a compound antiviral traditional Chinese medicine composition and a traditional Chinese medicine compound preparation that can safely and effectively prevent or treat viral infections.

[0005] The technical solution adopted by the present invention is:

[0006] A compound antiviral traditional Chinese medicine composition, wherein the compound traditional Chinese medicine composition comprises the following raw medicinal materials:

[0007] Artemisia annua, Scutellaria baicalensis, Forsythia suspensa, Talc, Artemisia capillaris, Acorus tatarinowii, Amomum kravanh, Gypsum fibrosum, Lepidium apetalum, Perilla leaf, Pinellia ternata processed with ginger, and Six-Flavor Fermented Medicinal Leaven.

[0008] Further, the compound antiviral traditional Chinese medicine composition is composed of the following raw medicinal materials in parts by weight: 200-400 parts of Artemisia annua, 120-200 parts of Scutellaria baicalensis, 150-250 parts of Forsythia suspensa, 450-650 parts of talc, 200-400 parts of Artemisia capillaris, 150-250 parts of Acorus tatarinowii, 120-200 parts of Amomum kravanh, 450-650 parts of gypsum, 150-250 parts of Lepidium apetalum, 120-200 parts of Perilla leaf, 120-200 parts of Pinellia ternata processed with ginger, and 200-400 parts of stir-fried six-fermented medicinals.

[0009] Preferably, the compound antiviral traditional Chinese medicine composition is composed of the following raw medicinal materials in parts by weight: 230-275 parts of Artemisia annua, 130-175 parts of Scutellaria baicalensis, 185-215 parts of Forsythia suspensa, 475-560 parts of talc, 235-285 parts of Artemisia capillaris, 175-215 parts of Acorus tatarinowii, 135-170 parts of Amomum kravanh, 490-510 parts of gypsum, 175-240 parts of Lepidium apetalum, 140-175 parts of Perilla leaf, 135-175 parts of Pinellia ternata processed with ginger, and 220-280 parts of stir-fried six-fermented medicinals.

[0010] More preferably, the compound antiviral traditional Chinese medicine composition is composed of the following raw medicinal materials in parts by weight: 230-275 parts of Artemisia annua, 130-175 parts of Scutellaria baicalensis, 185-215 parts of Forsythia suspensa, 480-510 parts of talc, 235-285 parts of Artemisia capillaris, 175-215 parts of Acorus tatarinowii, 135-170 parts of Amomum kravanh, 500-510 parts of gypsum, 175-240 parts of Lepidium apetalum, 140-175 parts of Perilla leaf, 135-175 parts of Pinellia ternata processed with ginger, and 240-260 parts of stir-fried six-fermented medicinals.

[0011] Even more preferably, the compound antiviral traditional Chinese medicine composition is composed of the following raw medicinal materials in parts by weight: 250 parts of Artemisia annua, 150 parts of Scutellaria baicalensis, 200 parts of Forsythia suspensa, 500 parts of talc, 250 parts of Artemisia capillaris, 200 parts of Acorus tatarinowii, 150 parts of Amomum kravanh, 500 parts of gypsum, 200 parts of Lepidium apetalum, 150 parts of Perilla leaf, 150 parts of Pinellia ternata processed with ginger, and 250 parts of stir-fried six-fermented medicinals.

[0012] The present invention also provides an antiviral traditional Chinese medicine compound preparation prepared from the compound antiviral traditional Chinese medicine composition.

[0013] The dosage form of the antiviral traditional Chinese medicine compound preparation includes tablets, capsules, granules, dripping pills, pellets, decoctions or mixtures. The traditional Chinese medicine compound preparation can be prepared according to the conventional processes of pharmacy and pharmaceutically acceptable excipients for human use.

[0014] In the present application, preferably, the traditional Chinese medicine compound preparation can be a decoction or a mixture.

[0015] Further, when the antiviral traditional Chinese medicine compound preparation is a decoction or a mixture, it is prepared by the following method:

[0016] Take Artemisia annua, Scutellaria baicalensis, Forsythia suspensa, Talcum, Artemisia capillaris, Acorus calamus, Cardamom, Gypsum, Lepidium tiliaceum seed, Perilla leaf, Pinellia ternata, and scorched Liushenqu, add 4-5 times the mass of water and boil twice, the first time for 1.5-2 hours (preferably 1.5 hours) and the second time for 1-2 hours (preferably 1 hour), filter, combine the filtrate, and concentrate to a relative density of 1.10±0.05 at 60°C. Add ethyl paraben while hot, stir well, let stand, take the supernatant, and prepare it into a decoction or mixture.

[0017] When preparing a mixture, it is generally necessary to add ethylparaben as a pharmaceutical preservative.

[0018] The amount of ethylparaben added is generally 0.01 to 0.2% of the weight of all drugs.

[0019] When the antiviral Chinese medicine compound preparation is in the form of tablets, capsules, granules, dripping pills or pellets, it is prepared by the following method:

[0020] Take Artemisia annua, Scutellaria baicalensis, Forsythia suspensa, Talcum, Artemisia capillaris, Acorus calamus, Cardamom, Gypsum, Lepidium tiliaceum seed, Perilla leaf, Pinellia ternata, and Scorched Liushenqu, mix them in proportion and grind them into powder, add 60% ethanol by volume, the mass of ethanol being 20 to 25 times the weight of all the drugs, heat and reflux extraction for 3 times, each time for 1 to 2 hours, combine the obtained extracts, evaporate and recover the ethanol, and prepare the obtained extracts and pharmaceutical excipients acceptable to the human body into tablets, capsules, granules, micropills or dripping pills.

[0021] The present invention also provides use of the compound antiviral Chinese medicine composition or the compound antiviral Chinese medicine preparation in preparing medicines for preventing or treating viral infections.

[0022] In the present application, the viral infection may be a coronavirus infection. Furthermore, the coronavirus infection may be a novel coronavirus infection. The compound antiviral Chinese medicine composition or compound Chinese medicine preparation of the present application may be used to prevent or treat complications such as secondary infections and respiratory failure caused by the novel coronavirus. The compound Chinese medicine preparation of the present application may be used to prepare a drug for preventing or treating diseases such as fever and lung inflammation caused by the novel coronavirus.

[0023] The present invention also provides use of the compound antiviral Chinese medicine composition or the compound antiviral Chinese medicine preparation in preparing medicines for preventing or treating respiratory infections caused by viruses.

[0024] The formula of the compound Chinese medicine composition described in the present invention is derived from Hangzhou Xixi Hospital. This formula follows the basic principles of traditional Chinese medicine for treating diseases based on syndrome differentiation, selects raw material composition and dosage ratio, and ensures that the components can coordinate and promote each other, thereby achieving a synergistic and synergistic effect.

[0025] In the middle stage of COVID-19 infection, according to traditional Chinese medicine theory, the symptoms that appear are the blockage of the lungs by epidemic toxins. The specific clinical manifestations are persistent fever or alternating chills and fever, less cough with phlegm, or yellow phlegm, abdominal distension and constipation. Chest tightness and shortness of breath, cough and wheezing, and shortness of breath on movement. The tongue is light or light red, the tongue coating is yellow and greasy or yellow and dry, and the pulse is slippery and rapid. In the middle stage, the epidemic toxin turns into heat and penetrates deeply, stagnating and blocking Shaoyang Sanjiao. Dampness combines with heat, heat is more severe than dampness, or dampness and heat are equally severe. The qi mechanism is blocked, the ascending and descending are abnormal, and body fluids are consumed, resulting in persistent fever or alternating chills and fever, less cough with phlegm, or yellow phlegm, abdominal distension and constipation, chest tightness and shortness of breath, cough and wheezing, and shortness of breath on movement. The light or light red tongue, yellow and greasy or yellow and dry tongue coating, and slippery and rapid pulse are signs of the transformation of cold-dampness into heat. The pathogenesis of this syndrome generally belongs to the blockage of the lungs by epidemic toxins and the internal accumulation of dampness and heat. The treatment principle is to clear heat and detoxify, promote diuresis and resolve turbidity, and regulate the qi mechanism. In the formula of this invention, Artemisia annua, Scutellaria baicalensis, and Forsythia suspensa are used to clear the heat of the liver, gallbladder, lungs, and stomach, and regulate the pivot. Talc and Artemisia capillaris clear heat and promote diuresis below, clearing above and seeping below to separate and eliminate dampness and heat. The combination of Acorus tatarinowii, Amomum kravanh, Pinellia ternata, and Gypsum fibrosum is used to relieve the entrapment of dampness and heat in the middle jiao. Lepidium apetalum not only purges the phlegm-fire and relieves cough and asthma by expelling phlegm and fluid in the lungs, but also relieves the obstruction of the lung qi and regulates the water passages, being a powerful medicine for resolving turbidity. Perilla frutescens and Six-Fried Medicated Leaven awaken the spleen, soothe the middle jiao, promote digestion and accumulate food to protect the stomach qi. With the stomach qi present, there is vitality. The whole formula communicates the upper and lower parts, clears heat and promotes diuresis, and regulates the qi mechanism, so that "the upper jiao is unblocked, and body fluids can descend" to relieve the blockage of the lungs by epidemic toxins.

[0026] The traditional Chinese medicine compound preparation provided by the present invention has the following main functions during the clinical treatment of COVID-19 infection: intervening in the middle stage to block the disease course; significantly alleviating symptoms; shortening the fever time and hospitalization time; promoting the absorption of inflammation and reducing sequelae; reducing complications and the toxic and side effects of western medicines. From the perspective of clinical application, after the patients being treated in the hospital receive combined traditional Chinese and western medicine treatment, the symptoms are significantly improved, the number of patients developing into severe cases is small, and the prognosis is good.

[0027] In summary, the compound traditional Chinese medicine composition and the traditional Chinese medicine compound preparation of the present invention have great application potential and practical significance in the treatment of the middle stage of virus-related pneumonia. Developing and preparing it into a traditional Chinese medicine mixture by traditional technology and further promoting its application have good social benefits and application value. Detailed Embodiments

[0028] To make the purpose, technical solutions, and advantages of the present application clearer, the embodiments of the present application are described in detail below. It should be noted that, without conflict, the embodiments and features in the embodiments of the present application can be combined arbitrarily with each other.

[0029] Example 1

[0030] Take 125 g of Artemisia annua, 75 g of Scutellaria baicalensis, 100 g of Forsythia suspensa, 250 g of Talc, 125 g of Artemisia capillaris, 100 g of Acorus tatarinowii, 75 g of Amomum kravanh, 250 g of Gypsum Fibrosum, 100 g of Lepidium apetalum, 75 g of Perilla frutescens, 75 g of Pinellia ternata processed with ginger, 125 g of Medicated Leaven. The above twelve flavors are decocted twice with 4900 g of water. The first decoction is for 1.5 hours and the second is for 1 hour. Filter, combine the filtrates, concentrate to a relative density of about 1.10 (60 °C) for the concentrated solution, add 0.5 g of ethylparaben while it is hot, stir well, let stand, take the supernatant, add water to 1000 ml, stir well, dispense, sterilize, and make into a mixture, thus obtaining it.

[0031] Example 2

[0032] Take 205 g of Artemisia annua, 120 g of Scutellaria baicalensis, 180 g of Forsythia suspensa, 550 g of Talc, 225 g of Artemisia capillaris, 160 g of Acorus tatarinowii, 175 g of Amomum kravanh, 560 g of Gypsum Fibrosum, 170 g of Lepidium apetalum, 175 g of Perilla frutescens, 165 g of Pinellia ternata processed with ginger, 215 g of Medicated Leaven. The above twelve flavors are decocted twice with 4 times the mass of water. The first decoction is for 1.5 hours and the second is for 1 hour. Filter, combine the filtrates, concentrate to an appropriate amount, add 0.8 g of ethylparaben while it is hot, stir well appropriately, let stand, take the supernatant, add water to 1900 ml, stir well, dispense, sterilize, and make into a mixture, thus obtaining it.

[0033] Example 3

[0034] Take 365 g of Artemisia annua, 175 g of Scutellaria baicalensis, 220 g of Forsythia suspensa, 620 g of Talc, 375 g of Artemisia capillaris, 190 g of Acorus tatarinowii, 185 g of Amomum kravanh, 630 g of Gypsum Fibrosum, 240 g of Lepidium apetalum, 195 g of Perilla frutescens, 190 g of Pinellia ternata processed with ginger, 375 g of Medicated Leaven. The above twelve flavors are decocted twice with 4 times the mass of water. The first decoction is for 2.5 hours and the second is for 2 hours. Filter, combine the filtrates, concentrate to an appropriate amount, add 2.5 g of ethylparaben while it is hot, stir well appropriately, let stand, take the supernatant, add water to 1900 ml, stir well, dispense, sterilize, and make into a mixture, thus obtaining it.

[0035] Example 4

[0036] Take 300 g of Artemisia annua, 165 g of Scutellaria baicalensis, 205 g of Forsythia suspensa, 570 g of Talc, 310 g of Artemisia capillaris, 185 g of Acorus tatarinowii, 165 g of Amomum kravanh, 600 g of Gypsum Fibrosum, 210 g of Lepidium apetalum, 165 g of Perilla frutescens, 190 g of Pinellia ternata processed with ginger, and 375 g of Six-Flavor Medicinal Leaven. After mixing the above twelve flavors in proportion, grind them into powder, add ethanol with a volume fraction of 60%, and the mass ratio of ethanol is 20 times the weight of all drugs. Heat under reflux for extraction 3 times, 1.5 hours each time. Combine the obtained extracts, evaporate and recover ethanol to obtain 616 g of a traditional Chinese medicine extract. Take 600 g of the above traditional Chinese medicine extract, add 350 g of dextrin, mix evenly, use 80% ethanol solution + 3.5% polyvinylpyrrolidone, which is 35% of the total amount of the mixture, as a binder to prepare soft materials, dry at 55 °C, crush and pass through a 10-mesh sieve to make granules, and you will get the product.

[0037] Example 5

[0038] Take 360 g of Artemisia annua, 155 g of Scutellaria baicalensis, 225 g of Forsythia suspensa, 590 g of Talc, 320 g of Artemisia capillaris, 155 g of Acorus tatarinowii, 155 g of Amomum kravanh, 560 g of Gypsum Fibrosum, 180 g of Lepidium apetalum, 155 g of Perilla frutescens, 165 g of Pinellia ternata processed with ginger, and 355 g of Six-Flavor Medicinal Leaven. After mixing the above twelve flavors in proportion, grind them into powder, add ethanol with a volume fraction of 60%, and the mass ratio of ethanol is 25 times the weight of all drugs. Heat under reflux for extraction 3 times, 1.5 hours each time. Combine the obtained extracts, evaporate and recover ethanol to obtain 705 g of a traditional Chinese medicine extract. Take 700 g of the above traditional Chinese medicine extract, add 250 g of starch and 15 g of magnesium stearate, mix well, use 90% ethanol solution as a wetting agent to granulate, pass through a 16-mesh sieve, press into tablets, and coat with ethylcellulose to make tablets, and you will get the product.

[0039] Example 6

[0040] Take 30 g of Artemisia annua, 175 g of Scutellaria baicalensis, 215 g of Forsythia suspensa, 570 g of Talc, 300 g of Artemisia capillaris, 185 g of Acorus tatarinowii, 155 g of Amomum kravanh, 580 g of Gypsum Fibrosum, 200 g of Lepidium apetalum, 175 g of Perilla frutescens, 160 g of Pinellia ternata processed with ginger, and 365 g of Six-Flavor Medicinal Leaven. After mixing the above twelve flavors in proportion, grind them into powder, add ethanol with a volume fraction of 60%, and the mass ratio of ethanol is 20 times the weight of all drugs. Heat under reflux for extraction 3 times, 1.5 hours each time. Combine the obtained extracts, evaporate and recover ethanol, and concentrate into a thick paste. Take an appropriate amount of polyethylene glycol 6000, heat it to melt, add the above thick paste, mix well, and drop it into cooled liquid paraffin at a dropping speed of 90 - 100 drops / min to make dripping pills, and you will get the product.

[0041] Example 7

[0042] Take 215 g of Artemisia annua, 140 g of Scutellaria baicalensis, 180 g of Forsythia suspensa, 590 g of Talc, 210 g of Artemisia capillaris, 165 g of Acorus tatarinowii, 145 g of Amomum kravanh, 560 g of Gypsum Fibrosum, 170 g of Lepidium apetalum, 145 g of Perilla frutescens, 130 g of Pinellia ternata (processed with ginger), and 285 g of Six-Flavors Medicated Leaven. The above twelve herbs are mixed in proportion and ground into a powder. Then, add ethanol with a volume fraction of 60%, and the mass ratio of ethanol is 20 times the weight of all the herbs. Heat under reflux for extraction 3 times, each time for 1.5 hours. Combine the obtained extracts, evaporate and recover ethanol, concentrate and dry under reduced pressure at 0.09 Mpa, dry in a vacuum drying oven, pulverize into a fine powder, sieve, and fill into capsules to obtain the capsule preparation.

[0043] Example 8

[0044] According to the clinical use situation of the preparation from before the record-filing application to after the record-filing, that is, from January to the end of February 2020, our hospital conducted a phased analysis and summary of its curative effect.

[0045] Specifically as follows:

[0046] Adopt the research plan of a randomized controlled trial to evaluate and summarize the clinical curative effect of the traditional Chinese medicine compound preparation of the present invention in the treatment of novel coronavirus infection. Use the mixture prepared in Example 1.

[0047] I. Data and Methods

[0048] 1 Case Selection

[0049] 1.1 Inclusion Criteria

[0050] Select 60 patients who were hospitalized in our hospital from January 2020 to February 2020 and met the diagnostic criteria of the "Diagnosis and Treatment Plan for Novel Coronavirus Infection" to be included in the study. They met the following inclusion criteria: (1) Met the diagnostic criteria; (2) Aged 18 - 90 years old; (3) The diagnostic classification belonged to the mild or severe type.

[0051] 1.2 Exclusion Criteria

[0052] Patients with extremely severe type; patients under 18 years old; pregnant and lactating women; patients with a history of food and drug allergies.

[0053] 1.3 Exclusion Criteria

[0054] Patients with poor compliance and those who did not sign the informed consent form.

[0055] 1.4 Curative Effect Judgment Criteria

[0056] Recovery: All pulmonary lesions are absorbed, and the oxygen saturation SpO2 > 98%;

[0057] Marked Effect: Most of the pulmonary lesions are absorbed (>70%), and the oxygen saturation SpO2 > 93%;

[0058] Effective: A small part of the lung lesions is absorbed (>30%), and SpO2 > 93% under high oxygen.

[0059] Ineffective: The condition deteriorates or death occurs.

[0060] 2 Research methods

[0061] The random parallel control method was adopted. There were 44 cases in the treatment group and 16 cases in the control group. The overall numbers of all drugs in the clinical trial were numbered from 001 to 060, and they were randomly numbered and grouped according to the order of case enrollment time.

[0062] 2.1 General treatment

[0063] Both groups of patients were given routine cardiopulmonary function and arterial blood gas analysis examinations at admission; clinical symptoms and signs were recorded; they were kept in bed for rest, support treatment was strengthened to ensure sufficient calories; attention was paid to the balance of water and electrolytes to maintain the stability of the internal environment.

[0064] 2.2 Drug administration treatment

[0065] The patients in the control group were given routine treatment according to the "Diagnosis and Treatment Plan for Novel Coronavirus Infection". The observation group was given the mixture of Example 1 of the traditional Chinese medicine compound preparation of the present invention on the basis of the routine treatment of the control group, twice a day, 50 mL each time.

[0066] 3 Efficacy observation indicators

[0067] The evaluation indicators for both groups of patients before and two weeks after medication included:

[0068] 3.1 Detection of biochemical indicators

[0069] Alanine aminotransferase (ALT), aspartate aminotransferase (AST), direct bilirubin (Dbil), total bilirubin (Tbil), albumin, lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase isoenzyme (CKMB).

[0070] 3.2 Blood routine + CRP + SAA detection

[0071] White blood cells (WBC), lymphocytes (L), neutrophils (R), high-sensitivity C-reactive protein (CRP), serum amyloid A (SAA).

[0072] 3.3 Coagulation function + D-dimer

[0073] Prothrombin time (PT), D-dimer (D-D).

[0074] 3.4 Blood gas analysis

[0075] Arterial partial pressure of oxygen (PaO2), oxygen saturation (SpO2).

[0076] 3.5 Imaging Observation

[0077] Observe the changes in the absorption of lung CT inflammation in the two groups of patients.

[0078] 4 Statistical Methods

[0079] Use SPSS 22.0 software. The data is expressed as and a two-sample t-test is performed. P < 0.05 indicates that the difference is statistically significant.

[0080] II. Results

[0081] 1 Analysis of the Baseline Characteristics of the Cases

[0082] A total of 60 cases were included in this study, with 44 cases in the treatment group and 16 cases in the control group. The age range was 18 to 85 years old, with an average of (43.73 ± 11.58) years. Among them, 39 were male, including 26 in the treatment group and 13 in the control group; 21 were female, including 10 in the treatment group and 11 in the control group.

[0083] 2 Efficacy Evaluation

[0084] 2.1 Temperature Changes in the Two Groups

[0085] After treatment with the antiviral mixture prepared in Example 1, the results of the fever reduction time of the patients are shown in Table 1. Compared with the control group, the number of days of fever reduction in the treatment group was statistically significant (p < 0.05).

[0086] Table 1 Comparison of Temperature Changes in the Two Groups

[0087]

[0088] Note: The traditional Chinese medicine compound preparation of the present invention was used as the treatment group, and the fever reduction time was shorter than that of the control group, * P < 0.05.

[0089] 2.2 Comparison of the Absorption of Lung Inflammation

[0090] Compared with the control group, after treatment with the traditional Chinese medicine compound preparation mixture of the present invention, the absorption of lung inflammation improved significantly, and the difference was statistically significant (p < 0.05). The results are shown in Table 2.

[0091] Table 2 Comparison of the Absorption of Lung Inflammation by X-ray or CT (cases, %)

[0092]

[0093] Note: Compared with the control group, the absorption of lung inflammation in the treatment group was more obvious, *P < 0.05.

[0094] 2.3 Comparison of Changes in Biochemical Indexes

[0095] The results of the biochemical indexes of the two groups of patients before and after treatment are shown in Table 3. Compared with the control group, after treatment with the traditional Chinese medicine compound preparation mixture of the present invention, each biochemical index of the treatment group was significantly improved, and the results were statistically significant (p < 0.05).

[0096] Table 3 Changes in blood biochemistry of the two groups before and after treatment

[0097]

[0098]

[0099] Note: Compared with before treatment in the control group, *P < 0.05; compared with before treatment in the treatment group, # P < 0.05.

[0100] 2.4 Detection results of blood routine + CRP + SAA indexes

[0101] After treatment in the treatment group, the CRP and SAA indexes decreased and were lower than those in the control group, and the difference was statistically significant (p < 0.05). The results are shown in Table 4.

[0102] Table 4 Changes in blood routine of the two groups before and after treatment

[0103]

[0104] Note: Compared with before treatment in the control group, *P < 0.05; compared with before treatment in the treatment group, # P < 0.05.

[0105] 2.5 Changes in coagulation function + D-dimer indexes

[0106] The comparison of coagulation function and D-D indexes between the two groups before treatment is shown in Table 5, and the difference was not statistically significant (p > 0.05). After treatment in the treatment group, each index improved significantly, and the differences were all statistically significant (p < 0.05).

[0107] Table 5 Coagulation changes in the two groups before and after treatment

[0108]

[0109]

[0110] Note: Comparison of D-D dimer in the treatment group after treatment with that before treatment # P < 0.05; there was no statistical difference in each item of PT before and after treatment.

[0111] 2.6 Blood gas analysis before and after treatment

[0112] After treatment with the traditional Chinese medicine compound preparation mixture of the present invention, the blood gas of the patients was improved, and the results are shown in Table 6.

[0113] Table 6 Changes in blood gas before and after treatment in two groups

[0114]

[0115] Note: Comparison of SpO2 in the treatment group after treatment with that before treatment # P < 0.05; there were no statistically significant differences in each item of PaO2 before and after treatment.

[0116] 2.7 Results of clinical efficacy changes The clinical efficacy results of the traditional Chinese medicine compound preparation mixture of the present invention are shown in Table 7.

[0117] Table 7 Comparison results of clinical efficacy in two groups

[0118]

[0119] 3 Analysis of safety indicators

[0120] Among the 60 included patients, no clinical symptoms of adverse reactions occurred, and no abnormal indicators with clinical significance were found in safety indicators such as blood routine and liver function.

[0121] III. Summary and discussion

[0122] This study conducted a randomized controlled clinical trial, and the results showed that:

[0123] (1) The traditional Chinese medicine compound preparation of the present invention has a good effect on the treatment of novel coronavirus infection. During the treatment period, the recovery ratios of blood routine, biochemical indicators, and inflammation indicators of the patients in the treatment group were positively correlated with the treatment time, and the normal recovery rates of each indicator were significantly higher than those of the control group (p < 0.05).

[0124] (2) The traditional Chinese medicine compound preparation of the present invention also has an obvious effect on improving the pulmonary inflammation of patients with novel coronavirus infection. After 2 weeks of treatment observed by pulmonary CT, the absorption of pulmonary inflammation and the absorption of pulmonary patchy shadows in the treatment group were significantly improved compared with the control group (p < 0.05).

[0125] In summary, the traditional Chinese medicine compound preparation of this patent has a good therapeutic effect on the middle-stage patients with novel coronavirus infection and has no obvious toxic and side effects.

[0126] Example 9

[0127] To further confirm the rationality of the prescription in this patent, we conducted screening of the combination of several medicinal materials, including Amomum kravanh, Lepidium apetalum, and Perilla leaf. Using ribavirin injection as a positive control, at the cellular level, the MTT method was employed to study the inhibitory effect of the traditional Chinese medicine preparation in this prescription on common respiratory infection viruses in vitro.

[0128] Culture medium: DMEM medium + fetal bovine serum

[0129] Cell lines and virus strains: Hep-2 (human laryngeal cancer cells, the host cells for RSV and Coxsackievirus B5), respiratory syncytial virus (RSV), and Coxsackievirus B5 (CV-B5) were provided by the Institute of Basic Medicine, Zhejiang Academy of Medical Sciences. Cell culture medium: Take 500 ml of DMEM medium, add 60 ml of fetal bovine serum and 2 ml of double antibiotics, mix well, and store at 4°C. Cell maintenance medium: Dilute the cell culture medium 5-fold with DMEM medium.

[0130] Experimental method:

[0131] Preparation of the test drug solution: Take the traditional Chinese medicine mixture in Example 1 as Test Drug 1. Additionally, prepare Test Drug 2 according to the method in Example 1 (compared with Test Drug 1, the difference is that it does not contain Amomum kravanh), Test Drug 3 (compared with Test Drug 1, the difference is that it does not contain Lepidium apetalum and Perilla leaf), and Test Drug 4 (compared with Test Drug 1, the difference is that it does not contain Lepidium apetalum). The test drugs were filtered through a 0.22 μm microporous filter membrane and stored at -20°C in the refrigerator for later use.

[0132] Preparation of the positive control drug: The ribavirin injection was used in its original solution with a concentration of 50 mg / ml.

[0133] Cell resuscitation and virus amplification: Take out the cryopreservation tube containing Hep-2 cells from the liquid nitrogen tank and immediately immerse it in warm water at 37°C - 42°C to melt, allowing the cells to quickly pass through the freeze-thaw process. In the laminar flow hood, transfer the cell suspension to a centrifuge tube for centrifugation, and then transfer the cell suspension to a culture flask and culture it in a carbon dioxide incubator. Take cells in the exponential growth phase with good condition, discard the culture medium, wash 3 times with PBS, add 0.6 ml of virus solution, and continue to culture in the carbon dioxide incubator. Gently shake the culture flask every 20 minutes to ensure full contact and uniform mixing. Additionally, set up a cell control group, add 0.6 ml of cell maintenance medium, and culture it in the same way as above. After culturing for 1 hour, supplement with 5 ml of cell maintenance medium and continue culturing. After 24 hours, conduct microscopic examination. When the number of infected and diseased cells is greater than 90%, stop culturing. Freeze and thaw the cells repeatedly, transfer, centrifuge (1000 r / min, 5 min), take the supernatant, quantitatively aliquot it into cryopreservation tubes, and store at -80°C for later use.

[0134] Determination of virus virulence: The amplified virus mentioned above was serially diluted 10-fold with 2% maintenance fluid for 10 gradients, and 4 longitudinal replicates were set for each dilution. Then it was inoculated into a 96-well plate with monolayer Hep-2 cells. At the same time, cell control and blank control were set. It was cultured in a virus incubator at 37°C and 5% CO2. Observation was carried out under an inverted microscope, and the culture was terminated when more than 90% of the cells showed cytopathic effect. According to the operation of the Cell Counting Kit-8 kit (10 μL of CCK-8 staining solution was added to each well and cultured in a virus incubator at 37°C and 5% CO2 for 3 h, and the absorbance A was measured at a wavelength of 450 nm with an enzyme-linked immunosorbent assay instrument), and the median infectious dose TCID of the virus solution was calculated according to the Reed-Muench formula 50 , and the results are shown in Table 8. The cytopathic rate = 1 - cell survival rate, and the survival rate = (A value of the diseased well - A value of the blank well) / (A value of the cell control well - A value of the blank well). The ratio distance = (higher than 50% survival rate - 50%) / (higher than 50% survival rate - lower than 50% survival rate), and CID 50 = Antilg(Ig of the virus dilution with a higher than 50% CPE percentage + logarithm of the dilution factor × ratio distance).

[0135] Table 8 Results of virus virulence

[0136]

[0137] Antiviral experiment of the test drug: The test drug was diluted 10-fold in a two-fold ratio with 2% maintenance fluid to obtain 10 concentration gradients, and interacted with an equal volume of virus solution with 100-fold TCID 50 for 2 h. Then 100 μL of each was inoculated into a 96-well plate with monolayer cells in sequence, and 4 replicates, cell control wells, positive control wells and blank control wells were set. It was cultured in a virus incubator at 37°C and 5% CO2. Observation was carried out under an inverted microscope, and the culture was terminated when 90% of the cells showed cytopathic effect. According to the operation of the CCK-8 kit, the absorbance A was measured, the cell survival rate was calculated, and the median effective concentration (EC 50 ) and therapeutic index (TI) of the drug were calculated using the Reed-Muench formula, and the results are shown in Table 9. EC 50 = [Antilog(log value of the virus dilution with a higher than 50% CPE percentage - ratio distance)] × C2 (C2 is the drug concentration of the first well), and the therapeutic index (TI = median toxic concentration (TC 50 ) / median effective concentration (EC 50 ).

[0138] Table 9 Bactericidal effect of the drug on the virus( n = 4)

[0139]

[0140]

[0141] Note: Compared with the positive drug group, *P < 0.05.

[0142] Results and Discussion: The experiment showed that the test drugs had direct killing effects on both RSV and COX-B5 (TI > 4, having a killing effect). Test drug 1 had a relatively good direct killing effect on RSV, with a TI value of 14.383, which was not much different from that of the positive control drug ribavirin (TI value of 14.102); test drug 1 had a direct killing effect on COX-B5, with a TI value of 15.054, which was better than that of the positive control drug ribavirin (TI value of 14.005); when cardamom was missing in the prescription (test drug 2), or when semen lepidii and folium perillae were missing (test drug 3), or when semen lepidii was missing (test drug 4), their TI values were all less than that of the positive control, and the antiviral effect was poor compared with the positive control acyclovir.

Claims

1. A compound traditional Chinese medicine composition for anti-virus, characterized in that The compound traditional Chinese medicine composition for anti-virus is composed of the following raw medicinal materials in parts by weight: 250 parts of Artemisia annua, 150 parts of Scutellaria baicalensis, 200 parts of Forsythia suspensa, 500 parts of Talc, 250 parts of Artemisia capillaris, 200 parts of Acorus tatarinowii, 150 parts of Amomum kravanh, 500 parts of Gypsum Fibrosum, 200 parts of Lepidium apetalum, 150 parts of Perilla leaf, 150 parts of Pinellia ternata processed with ginger, and 250 parts of Six-Flavored Fermented Medicinal Leaven.

2. An anti-viral traditional Chinese medicine compound preparation prepared from the compound traditional Chinese medicine composition for anti-virus according to claim 1.

3. The antiviral traditional Chinese medicine compound preparation according to claim 2, characterized in that The dosage forms of the anti-viral traditional Chinese medicine compound preparation include tablets, capsules, granules, pellets, dripping pills, decoctions or mixtures.

4. Use of the compound traditional Chinese medicine composition for anti-virus according to claim 1 or the anti-viral traditional Chinese medicine compound preparation according to claim 2 in the preparation of a drug for preventing or treating viral infections.

5. The application according to claim 4, characterized in that The virus is respiratory syncytial virus or Coxsackievirus B5.

6. Use of the compound traditional Chinese medicine composition for anti-virus according to claim 1 or the anti-viral traditional Chinese medicine compound preparation according to claim 2 in the preparation of a drug for preventing or treating coronavirus infections.

7. Use of the compound traditional Chinese medicine composition for anti-virus according to claim 1 or the anti-viral traditional Chinese medicine compound preparation according to claim 2 in the preparation of a drug for preventing or treating respiratory infections caused by viruses.

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