A Chinese medicine composition for preventing novel coronavirus infection and its preparation method and application

Abstract

The present invention discloses a Chinese medicine composition for preventing novel coronavirus infection, which is prepared from the following raw materials in parts by weight: 5-20 of five-fingered peach, 2-8 of dandelion, 1-5 of angelica dahurica, 3-10 of patchouli, and 7-15 of reed root. The Chinese medicine composition has the effects of strengthening the spleen, removing dampness, and eliminating filth. Clinical trials have shown that it can significantly reduce the incidence of new coronary pneumonia infection in the social population and close contact population. The incidence rate within 7 days and the incidence rate within 7-14 days of Chinese medicine intervention are lower than those in the control group, and the close contact population can be relieved of anxiety, insomnia, and mild symptoms of poor appetite, with significant effects. In addition, the present invention also discloses a preparation method and use of the Chinese medicine composition.

Description

Technical Field

[0001] The present invention relates to a traditional Chinese medicine composition for preventing novel coronavirus infection. In addition, the present invention also relates to a preparation method and use of the traditional Chinese medicine composition. Background Art

[0002] According to the "New Coronavirus Pneumonia Diagnosis and Treatment Plan (Trial Ninth Edition)", the new coronavirus (SARS-CoV-2) belongs to the β-genus coronavirus, has an envelope, and the particles are round or oval with a diameter of 60 to 140nm. It has 5 essential genes, targeting four structural proteins: nucleoprotein (N), viral envelope (E), matrix protein (M) and spike protein (S) and RNA-dependent RNA polymerase (RdRp). The nucleoprotein (N) wraps the RNA genome to form the nucleocapsid, which is surrounded by the viral envelope (E). The viral envelope is embedded with proteins such as matrix protein (M) and spike protein (S). The spike protein enters the cell by binding to angiotensin-converting enzyme 2 (ACE-2). When isolated and cultured in vitro, the new coronavirus can be found in human respiratory epithelial cells in about 96 hours, while it takes about 4 to 6 days to isolate and culture in Vero E6 and Huh-7 cell lines.

[0003] Like other viruses, the genome of the new coronavirus will also mutate, and some mutations will affect the biological characteristics of the virus. For example, changes in the affinity of the S protein to ACE-2 will affect the ability of the virus to invade cells, replicate, and spread, the production of antibodies during the recovery period and after vaccination, and the neutralizing ability of antibody drugs, which has attracted widespread attention. The World Health Organization (WHO) has proposed five "variants of concern" (VOC), namely Alpha, Beta, Gamma, Delta, and Omicron. At present, cases of infection with the Omicron strain have replaced the Delta strain as the main epidemic strain. Existing evidence shows that the Omicron strain is more transmissible than the Delta strain, and its pathogenicity has been weakened. The diagnostic accuracy of the PCR test routinely used in my country has not been affected, but it may reduce the neutralizing effect of some monoclonal antibody drugs on it.

[0004] Coronavirus belongs to the Coronaviridae family and the Coronavirus genus in terms of systematic classification. Coronavirus is a positive-stranded single-stranded RNA virus with an envelope. Its genetic material is the largest among all RNA viruses and generally only infects humans, mice, pigs, cats, dogs, and avian vertebrates. The existence of coronavirus poses a serious threat to the survival and health of humans and animals, and has a serious impact on global economic development.

[0005] As a new and highly contagious disease, our understanding of novel coronavirus pneumonia needs to be continuously explored and improved, but there is currently no specific medicine.

[0006] People infected with the Omicron variant of the new coronavirus are mainly asymptomatic.

[0007] Since the outbreak of the novel coronavirus pneumonia (COVID-19), traditional Chinese medicine has played an important role in prevention. In view of the characteristics of the novel coronavirus infection, especially the Omicron variant, which spreads rapidly and is asymptomatic, we need drugs that can prevent the disease in the social population and close contacts, reduce the incidence rate, and improve anxiety. Summary of the invention

[0008] In view of the above-mentioned deficiencies in the prior art, according to an embodiment of the present invention, it is hoped to provide a Chinese medicine composition for preventing novel coronavirus infection, aiming to prevent novel coronavirus infection, reduce the incidence of social groups and close contacts, and alleviate the mild symptoms caused by their anxiety. In addition, it is also hoped to propose a preparation method and use of the Chinese medicine composition

[0009] According to the embodiments, the present invention provides a traditional Chinese medicine composition for preventing novel coronavirus infection, which is prepared from the following raw materials in parts by weight: 5-20 parts of quinquefolius, 2-8 parts of dandelion, 1-5 parts of angelica dahurica, 3-10 parts of patchouli, and 7-15 parts of reed root.

[0010] Preferably, in the aforementioned traditional Chinese medicine composition for preventing novel coronavirus infection of the present invention, the weight portions of the raw materials are: 10-14 parts of quinquefolius, 4-8 parts of dandelion, 1-4 parts of angelica dahurica, 4-7 parts of patchouli, and 8-12 parts of reed root; more preferably, the weight portions of the raw materials are: 12 parts of quinquefolius, 6 parts of dandelion, 3 parts of angelica dahurica, 6 parts of patchouli, and 9 parts of reed root.

[0011] Preferably, the aforementioned traditional Chinese medicine composition for preventing novel coronavirus infection of the present invention can be prepared into decoction, tablet, capsule, powder, granule, oral liquid, pill, tincture, syrup, suppository, gel, spray or injection according to conventional methods.

[0012] According to the embodiments, the present invention provides a method for preparing a decoction of a traditional Chinese medicine composition for preventing infection with the new coronavirus, comprising the following steps: weighing 12 pieces of quinquefolius, 6 pieces of dandelion, 3 pieces of angelica dahurica, 6 pieces of patchouli, and 9 pieces of reed root according to the selected weight portions, adding 4-7 times the amount of water and decocting twice, each time for 0.5-2 hours, combining the decoctions, filtering, and concentrating to 2-4 times the amount to obtain the decoction.

[0013] According to an embodiment, the present invention provides a method for preparing a Chinese medicine composition granule for preventing novel coronavirus infection, comprising the following steps:

[0014] A. Weigh dandelion and patchouli by weight, mix, add 5-8 times the amount of water to extract volatile oil, extract the oil for 4-6 hours, collect the volatile oil and set aside; after filtering the extract, discard the residue and set aside the filtrate;

[0015] B. Weigh five-fingered peach, reed root and angelica dahurica by weight, add 5-8 times the amount of water and boil twice, each time for 1-2 hours, filter the extract, discard the residue, and use the filtrate for later use;

[0016] C. Combine the extracts of step A and B, concentrate, let stand to settle, filter, spray-dry the filtrate, collect the spray-dried powder, add the volatile oil obtained in step A, mix well, and obtain the product.

[0017] According to an embodiment, the present invention provides a method for preparing a Chinese medicine composition capsule for preventing novel coronavirus infection, comprising the following steps:

[0018] A. Weigh dandelion and patchouli by weight, mix, add 5-8 times the amount of water to extract volatile oil, extract the oil for 4-6 hours, collect the volatile oil and set aside; after filtering the extract, discard the residue and set aside the filtrate;

[0019] B. Weigh five-fingered peach, reed root and angelica dahurica by weight, add 5-8 times the amount of water and boil twice, each time for 1-2 hours, filter the extract, discard the residue, and use the filtrate for later use;

[0020] C. Combine the filtrates from step A and step B, concentrate, dry and set aside;

[0021] D. Add ethanol to dissolve the volatile oil obtained in step A, spray it into the dry powder obtained in step C, add pharmaceutically acceptable excipients, granulate, dry at low temperature, and put into capsules to obtain the product.

[0022] Subsequent examples, test cases and clinical trials show that the Chinese medicine composition of the present invention [Strengthening the body and preventing epidemics] can significantly reduce the incidence of COVID-19 infection in the social population and close contact population. The incidence rate within 7 days and the incidence rate within 7-14 days of Chinese medicine intervention are lower than those in the control group, and can alleviate the mild symptoms of anxiety, insomnia and poor appetite in the close contact population, with significant effects. Relative to the prior art, the Chinese medicine composition of the present invention is obtained through clinical trials based on the clinical characteristics of the novel coronavirus Omicron variant, on the basis of the classic prescription. The present invention is based on the "Warm Disease Treatise" "Warm epidemics, severe air prevalence, many with foul turbidity, every family is like this, as if it is caused by slavery", combined with the characteristics of the novel coronavirus infected person, especially the characteristics of the Omicron variant infected person. It is believed that this disease belongs to "warm disease", which is often accompanied by foul turbidity and highly contagious. To prevent this disease, the treatment should be to strengthen the spleen, eliminate dampness, and eliminate filth. The Chinese medicine composition of the present invention uses five-fingered peach as the main ingredient for strengthening the spleen and lungs, promoting qi and removing dampness; white angelica dahurica dispels cold, dispels wind and relieves pain; dandelion and patchouli dry out dampness and dispel filth, penetrate the surface and expel evil, and are all assistant ingredients; reed root clears heat and promotes body fluid as the adjuvant ingredient. The whole prescription consolidates the root and expels evil, removes turbidity and dispels filth, and implies the idea of ​​preventing disease before getting sick. All the medicines work together to strengthen the spleen, remove dampness, and dispel filth, and are mainly used to protect the positive energy and prevent plague. It plays an active preventive role in coronavirus infection. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 A flow chart showing the experiment flow for different population time periods.

[0024] Figure 2 Shows the population inclusion flow chart.

[0025] Figure 3 Shown are Kaplan–Meier estimates of the incidence rate at each time point for patients in the trial and control groups based on the entire population. DETAILED DESCRIPTION

[0026] The present invention is further explained below in conjunction with specific examples. It should be understood that these examples are only used to illustrate the present invention and are not used to limit the scope of the present invention. After reading the present invention, various equivalent modifications of the present invention by those skilled in the art all fall within the scope defined by the claims attached to this application.

[0027] If no specific experimental steps or conditions are specified in the examples, the conventional experimental steps or conditions described in the literature in the field can be used. If no manufacturer is specified for the reagents or instruments used, they are all conventional reagent products that can be obtained commercially.

[0028] Example 1-5 (Preparation of decoction)

[0029] Weigh the weights of Prunus mume, dandelion, Angelica dahurica, Patchouli, and Phragmites australis listed in Table 0 respectively, decoct twice, add 600 ml of water each time, decoct for 1 hour each time, combine the decoctions, filter, and obtain 500 ml of decoction.

[0030] Table 0. Amount of each raw material medicine used in Examples 1-5

[0031]

[0032]

[0033] Example 6 (Preparation of decoction)

[0034] Weigh 12g of Prunus mume, 6g of Taraxacum mongolicum, 3g of Angelica dahurica, 6g of Patchouli, and 9g of Phragmites australis, decoct twice, add 500ml of water each time, decoct for 1 hour each time, combine the decoctions, filter, and obtain 400ml of decoction.

[0035] Example 7 (Preparation of decoction)

[0036] Weigh 12g of Prunus mume, 6g of dandelion, 3g of Angelica dahurica, 6g of Patchouli, and 9g of Phragmites australis, decoct twice in water, add 600ml of water each time, decoct for 0.5 hour each time, combine the decoctions, filter, and obtain 500ml of decoction.

[0037] Example 8 (Preparation of granules)

[0038] A. Weigh 600 g of patchouli and 600 g of dandelion, mix them, add 8 times the amount of water to extract the volatile oil, extract the oil for 5 hours, collect the volatile oil and set aside; after filtering the extract, discard the residue and set aside the filtrate;

[0039] B. Weigh 1200g of Prunus mume, 300g of Angelica dahurica and 900g of Phragmites australis, add 6 times the amount of water and boil twice, each time for 1.5 hours, filter the extract, discard the residue, and use the filtrate for standby use;

[0040] C. Combine the extracts, concentrate to a relative density of about 1.07 (80-85° C.), let stand to precipitate, filter, spray-dry the filtrate, collect the spray-dried powder, spray the volatile oil obtained in step A, mix well, and obtain the granules of the Chinese medicine composition of the present invention.

[0041] Example 9 (Preparation of capsules)

[0042] A. Weigh 600 g of patchouli and 600 g of dandelion, add 6 times the amount of water to extract volatile oil, extract for 6 hours, collect the volatile oil and set aside; after filtering the extract, discard the residue and set aside the filtrate;

[0043] B. Weigh 1200g of Prunus mume, 300g of Angelica dahurica, and 900g of Phragmites australis, add 8 times the amount of water and boil twice, each time for 1 hour, filter the extract, discard the residue, and use the filtrate for standby use;

[0044] C. Combine the extracts, concentrate to a relative density of about 1.15 (60-65°C), spray dry, and collect the spray-dried powder for later use;

[0045] D. Add ethanol to dissolve the volatile oil obtained in step A, spray the spray-dried powder obtained in step C, add dextrin, make granules, dry at low temperature, and put into capsules to obtain the Chinese medicine composition capsules of the present invention.

[0046] Test example (clinical treatment effect - the effect of the Chinese medicine composition of the present invention on preventing the social population from being infected with COVID-19)

[0047] 1 Materials and methods

[0048] 1.1 General Information

[0049] A total of 4405 healthy people or those with underlying diseases but no obvious discomfort were selected as research subjects. This study has been reviewed and approved by the Ethics Committee of Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (Ethics Approval No. 2022LCSY025).

[0050] Inclusion criteria: No physical discomfort symptoms; 16 years old and above; willing to take the medication recommended by this protocol or accept health survey. The subjects gave verbal informed consent.

[0051] Exclusion criteria: According to the clinical diagnosis and diagnosis criteria of the "New Coronavirus Pneumonia Diagnosis and Treatment Program (Trial Ninth Edition)" issued by the General Office of the National Health Commission and the General Office of the State Administration of Traditional Chinese Medicine, patients diagnosed as asymptomatic or confirmed cases who have not recovered. Patients with severe primary diseases of the cardiovascular, cerebrovascular, lung, kidney and hematopoietic systems; pregnant or lactating women; and patients with a history of allergy to prescribed drugs.

[0052] 1.2 Experimental Design This experiment is a cohort trial. 4405 healthy people or people with underlying diseases but no obvious discomfort were included and divided into an experimental group and a control group:

[0053] Test group: 2311 cases, received the decoction prepared by Example 1-7, once in the morning and evening (40 minutes after meal), warm and taken, 7 days as a course of treatment.

[0054] Control group: 2094 cases, no Chinese medicine intervention.

[0055] 1.3 Test methods

[0056] Record the patient's relevant data, including basic information on medication, clinical symptoms on days 0 and 7, nucleic acid test results, adverse reactions, etc. See the flowchart of this study for details. Figure 1 . A team of physicians with rich clinical experience evaluated and integrated data from different databases, and data reviewers verified the data without knowing the treatment regimen of the included subjects. To reduce the impact of selection bias on the results, cases were excluded only when data were missing for key variables (nucleic acid test results), otherwise they were included in the statistical analysis. The primary endpoint of this study was the comparison of incidence within 14 days after enrollment. Secondary endpoints included clinical symptom improvement rate, incidence within 7 days and 7-14 days after enrollment, and adverse events. On the basis of respecting the original data, the specific definitions are as follows:

[0057] The incidence rate within 14 days after enrollment, the improvement rate of clinical symptoms, the incidence rate within 7 days and 7-14 days after enrollment, and the occurrence of adverse events

[0058] Definition standard According to the clinical diagnosis and diagnosis standards of the "New Coronavirus Pneumonia Diagnosis and Treatment Plan (Trial Ninth Edition)" issued by the General Office of the National Health Commission and the Office of the State Administration of Traditional Chinese Medicine, the proportion of asymptomatic infections or confirmed cases diagnosed within 1-14 days of enrollment is the incidence rate within 14 days after enrollment. The proportion of asymptomatic infections or confirmed cases diagnosed within 1-7 days of enrollment is the incidence rate within 7 days after enrollment. The proportion of asymptomatic infections or confirmed cases diagnosed within 7-14 days of enrollment is the incidence rate within 7-14 days after enrollment. Those with persistent nucleic acid positive, those whose nucleic acid did not turn negative before enrollment, and those who did not have nucleic acid tests during enrollment or whose nucleic acid results were incomplete will be discussed separately, and those with missing data will be counted as "missing".

[0059] 1.4 Data Analysis

[0060] SPSS 25.0 software was used for statistical analysis, and P < 0.05 was considered statistically significant. 2 Continuous variables were described as median (interquartile range [IQR]), and the Mann-Whitney U test was used for comparison between two groups, and the Kruskal-Wallis H test was used for comparison between multiple groups. The baseline level of each group was adjusted, and the incidence rate 14 days after enrollment was used as the treatment outcome evaluation index to evaluate the difference in efficacy between different drug treatment groups.

[0061] 2. Test results

[0062] 2.1 Basic characteristics of patients

[0063] The flow chart of the population inclusion in this study is shown in Figure 2 A total of 4412 social personnel were included and divided into an intervention group and a control group. Three pregnant patients and four patients with positive nucleic acid who did not improve were excluded. A total of 4405 people were included in this study, of which 2311 patients in the intervention group received the decoction prepared in Examples 1-7, and 2094 patients in the control group did not receive Chinese medicine intervention.

[0064] The median age of the intervention group was 44 years old, with an IQR of (20-58) years old; the median age of the control group was 41 years old, with an IQR of (21-56) years old (P>0.05). There were 1800 males (77.8%) in the intervention group and 1667 males (79.6%) in the control group (P>0.05); there were 515 females (22.2%) in the intervention group and 427 females (20.4%) in the control group (P>0.05). There were 659 (28.5%) people in the intervention group and 547 (26.1%) people in the control group (P>0.05). There were 10 (0.4%) people in the intervention group and 8 (0.4%) people in the control group (P>0.05). There were 1453 (62.9%) people in the intervention group and 1365 (65.2%) people in the control group (P>0.05). There were 10 cases (0.4%) in the intervention group of people in the closed living area and 8 cases (0.4%) in the control group (P>0.05). There were 196 cases (8.5%) in the intervention group of close contacts and 187 cases (8.9%) in the control group (P>0.05). There were 1012 cases (43.8%) in the intervention group of secondary close contacts and 923 cases (44.1%) in the control group (P>0.05). There were 1103 cases (47.7%) in the intervention group of non-close contacts and 984 cases (47%) in the control group (P>0.05). See Table 1 for details.

[0065] In this study, 219 patients had mild discomfort, 99 patients had anxiety, 55 patients had insomnia, and 65 patients had poor appetite. There was no significant statistical difference between the two groups (P>0.05). See Table 2 for details.

[0066] Table 1. Basic characteristics of the population

[0067]

[0068] Table 2. Symptom characteristics of the enrolled population

[0069]

[0070] 2.2 Comparison of incidence rates in different time periods

[0071] There were 51 cases with positive nucleic acid test results from -10 to 0 days before the Chinese medicine intervention, and there were 2 or more consecutive negative tests after the last positive test. Among them, there were 30 cases (1.6%) in the intervention group and 21 cases (1.1%) in the control group. There was no significant statistical difference between the two groups (P>0.05).

[0072] Within 1-14 days of taking the medicine, 8 cases (0.3%) of the disease occurred in the intervention group and 37 cases (1.8%) of the disease occurred in the control group (P < 0.001). The RR value was 0.196 (0.091-0.420), and the excess risk was calculated to be -80.4%. Therefore, after taking Chinese medicine, the risk of infection with new coronary pneumonia decreased by 80.4%.

[0073] Within 1-7 days after enrollment, 8 cases (0.3%) of the disease occurred in the intervention group, and 23 cases (1.1%) of the disease occurred in the control group. There was a statistically significant difference between the two groups (P=0.003), and the RR value was 0.313 (0.141-0.703). The excess risk was calculated to be -68.7%. Therefore, after taking Chinese medicine, the risk of new coronary pneumonia infection decreased by 68.7%. Within 7-14 days after enrollment, 0 cases (0.0%) of the disease occurred in the intervention group, and 14 cases (0.2%) of the disease occurred in the control group (P<0.001).

[0074] The number of infections in the intervention group was concentrated on days 1-4, while the number of infections in the control group increased evenly from days 0 to 14. Figure 3 shown.

[0075] Table 3. Comparison of incidence rates in different time periods

[0076]

[0077] 2.3 Symptom improvement in the two groups of patients

[0078] After taking the medicine for 7 days, the symptoms of anxiety, insomnia and poor appetite in the intervention group were significantly improved compared with those in the control group, and the difference was statistically significant (P < 0.05).

[0079] Table 4. Comparison of symptom improvement after 7 days of medication

[0080]

[0081] 2.4 Adverse Reactions

[0082] During the follow-up period, 2 cases in the intervention group had adverse reactions, which were mild increased stool, and both resolved spontaneously. No adverse reactions caused by drugs occurred in the control group, and the chi-square test showed that there was no significant statistical significance between the two groups (P>0.05).

Claims

1. A Chinese medicine composition for preventing novel coronavirus infection, characterized in that: The invention is prepared from the following raw materials in parts by weight: 5-20 parts of quinquefolius, 2-8 parts of dandelion, 1-5 parts of angelica dahurica, 3-10 parts of patchouli and 7-15 parts of reed root.

2. The Chinese medicine composition for preventing novel coronavirus infection according to claim 1, characterized in that: The weight proportions of the raw materials are respectively: 10-14 parts of quinquefolius, 4-8 parts of dandelion, 1-4 parts of angelica dahurica, 4-7 parts of patchouli and 8-12 parts of reed root.

3. The Chinese medicine composition for preventing novel coronavirus infection according to claim 1, characterized in that: The weight proportions of the raw materials are respectively: 12 parts of quinquefolius, 6 parts of dandelion, 3 parts of angelica dahurica, 6 parts of patchouli and 9 parts of reed root.

4. The Chinese medicine composition for preventing novel coronavirus infection according to any one of claims 1 to 3, characterized in that: The dosage form of the Chinese medicine composition is a decoction, tablet, capsule, powder, granule, oral liquid, pill, tincture, syrup, suppository, gel, spray or injection prepared according to conventional methods.

5. A method for preparing a decoction of a Chinese medicine composition for preventing novel coronavirus infection as claimed in claim 4, characterized in that: The method comprises the following steps: weighing five-fingered peach, dandelion, angelica dahurica, patchouli and reed root according to weight, adding 4-7 times amount of water and boiling twice, each time for 0.5-2 hours, combining the decoctions, filtering and concentrating to 2-4 times amount to obtain the product.

6. A method for preparing the Chinese medicine composition granules for preventing novel coronavirus infection as claimed in claim 4, characterized in that: The steps include: A. Weigh dandelion and patchouli by weight, mix, add 5-8 times the amount of water to extract volatile oil, extract the oil for 4-6 hours, collect the volatile oil and set aside; after filtering the extract, discard the residue and set aside the filtrate; B. Weigh five-fingered peach, reed root and angelica dahurica by weight, add 5-8 times the amount of water and boil twice, each time for 1-2 hours, filter the extract, discard the residue, and use the filtrate for later use; C. Combine the filtrates from step A and B, concentrate, allow to settle, filter, spray-dry the filtrate, collect the spray-dried powder, add the volatile oil obtained from step A, mix well, and obtain the product.

7. A method for preparing a Chinese medicine composition capsule for preventing novel coronavirus infection as claimed in claim 4, characterized in that: The steps include: A. Weigh dandelion and patchouli by weight, mix, add 5-8 times the amount of water to extract volatile oil, extract the oil for 4-6 hours, collect the volatile oil and set aside; after filtering the extract, discard the residue and set aside the filtrate; B. Weigh five-fingered peach, reed root and angelica dahurica by weight, add 5-8 times the amount of water and boil twice, each time for 1-2 hours, filter the extract, discard the residue, and use the filtrate for later use; C. Combine the filtrates from step A and step B, concentrate, dry and set aside; D. Add ethanol to dissolve the volatile oil obtained in step A, spray it into the dry powder obtained in step C, add pharmaceutically acceptable excipients, granulate, dry at low temperature, and put into capsules to obtain the product.

8. Use of the Chinese medicine composition according to any one of claims 1 to 3 in the preparation of a medicament for preventing infection with the new coronavirus.

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