CN115554337A - Application of Reyanning in preparing medicine for treating infection of Omekron slight disease - Google Patents

Abstract

The invention relates to an application of Reyanning in preparing a medicine for treating Ormcken mild disease infection, which overcomes the problem that effective medicines for Omicron variant in the prior art are very limited. The invention comprises the application of the Yananning in preparing the medicine for treating the infection of the Ormcken palliative disease and the application of the Yananning in preparing the medicine for improving the cycle threshold (Ct) value of an Open Reading Frame (ORF) or nucleocapsid protein (N) gene of asymptomatic infected persons. The Reyanning is prepared from water extracts of dandelion, giant knotweed rhizome, patrinia scabiosaefolia and barbed skullcap herb, wherein the weight ratio of the dandelion, the giant knotweed rhizome, the patrinia scabiosaefolia and the barbed skullcap herb is 1-3. The medicine for treating the heat inflammation is prepared by the following preparation method: decocting the above four materials in water twice, the first time for 2 hr, the second time for 1 hr, filtering the decoction, concentrating the filtrate under reduced pressure to appropriate amount, mixing the concentrated solutions, centrifuging, filtering, adding steviosin 1.5g and ethylparaben 0.5g, heating to boil, and making into 1000 ml.

Description

Application of Reyanning in preparing medicine for treating infection of Omekron slight disease

The technical field is as follows:

the invention relates to an application of a traditional Chinese medicine composition, in particular to an application of Reyanning in preparing a medicine for treating infection of Onck Rongqing.

Background art:

some previous studies have shown that the variation of Oncorks is mainly asymptomatic and mild infection, and is accompanied by upper respiratory symptoms such as cough, expectoration, and fever. According to the diagnosis and treatment scheme for novel coronavirus pneumonia (nine pilot cases), mild cases are defined as mild clinical symptoms, and no imaging evidence indicates pneumonia.

The antiviral drugs for SARS-CoV-2 can be divided into two classes, monoclonal antibodies against Spike protein and small molecules that interfere with viral replication. Due to the high mutability of Spike protein, most of the currently approved monoclonal antibodies lose their neutralizing activity against SARS-CoV-2 Omicron. Currently small molecule antiviral drugs directed against SARS-CoV-2 conserved RdRp or Mpro are approved or licensed for Emergency Use (EUA) and are in clinical trials. Rudesavir and Mornuppivir are RdRp inhibitors of SARS-CoV-2, while nimorevir/ritonavir (Paxlovid) targets Mpro. Previous clinical studies have shown that early use of the above antiviral drugs can reduce the risk of hospitalization or death in high-risk adults with mild to moderate Covid-19, no vaccination, and no hospitalization. However, both of these tests exclude patients vaccinated with SARS-CoV-2 vaccine; therefore, these findings may not be applicable in areas with high vaccination rates. Currently, effective drugs against the omitron variant are very limited.

The invention content is as follows:

the invention aims to provide application of Reyanning in preparing a medicine for treating Oncurone mild disease infection, which overcomes the problem that effective medicines aiming at the Omicron variant in the prior art are very limited, and can improve the cycle threshold (Ct value) of an Open Reading Frame (ORF) or nucleocapsid protein (N) gene of a mild disease infected person in a short time.

In order to achieve the purpose, the invention adopts the technical scheme that:

application of Reyanning in preparing medicine for treating infection of Onck Rongqing disease.

Application of Reyanning in preparing medicine for increasing Open Reading Frame (ORF) or cycle threshold (Ct) value of nucleocapsid protein (N) gene of asymptomatic infected person is provided.

The Reyanning is prepared from water extracts of dandelion, giant knotweed rhizome, patrinia scabiosaefolia and barbed skullcap herb, wherein the weight ratio of the dandelion, the giant knotweed rhizome, the patrinia scabiosaefolia and the barbed skullcap herb is 1-3.

The medicine for treating the heat inflammation is prepared by the following preparation method: decocting the above four materials in water twice, the first time for 2 hr, the second time for 1 hr, filtering the decoction, concentrating the filtrate under reduced pressure to appropriate amount, mixing the concentrated solutions, centrifuging, filtering, adding steviosin 1.5g and ethylparaben 0.5g, heating to boil, and making into 1000 ml.

The dosage of the medicine for treating the hepatitis is as follows: the Chinese medicinal composition is administered 20ml from the first day 4 times daily for 7 days.

Compared with the prior art, the invention has the following advantages and effects:

1. the invention can improve the cycle threshold (Ct value) of the Open Reading Frame (ORF) or nucleocapsid protein (N) gene of a patient with mild disease in a shorter time. Is a safe and effective therapy for treating mild disease and mild disease Onckroshen infection, and can accelerate virus elimination and promote disease recovery.

2. The traditional Chinese medicine composition can be used for treating patients with mild infection. The cycle threshold (Ct value) of the Open Reading Frame (ORF) or nucleocapsid protein (N) gene of SARS-CoV-2 was detected by RT-PCR as a semi-quantitative viral load for analysis. And detecting the nucleic acid negative conversion rate, the nucleic acid negative conversion time and the hospitalization time of asymptomatic infectors, and the new symptoms and the virus load of asymptomatic patients through clinical tests. The curative effect of Reyanning mixture (RYN) on patients with mild Onck Rongzhen infection is comprehensively evaluated. The results show that RYN improves the nucleic acid negative conversion rate, shortens the nucleic acid negative conversion time and the hospitalization time, reduces new symptoms of asymptomatic patients and reduces the virus load. No serious adverse events were reported during the study. In conclusion, the traditional Chinese medicine composition has a remarkable treatment effect.

Description of the drawings:

FIG. 1 is a flow chart of the present invention;

FIG. 2 is a graph of audit negative conversion vs. KM analysis;

FIG. 3 is a graph showing the negative conversion rate of nucleic acids; (A) Comparing the nucleic acid negative conversion rate in two groups for 3 days, (B) comparing the nucleic acid negative conversion rate in two groups for 7 days;

FIG. 4 is a discharge rate-KM analysis chart;

FIG. 5 is a graph showing the change in the circulating threshold (Ct) of SARS-CoV-2 viral load during the course of observation; (A) Ct value of ORF gene, (B) Ct value of N gene;

FIG. 6 is a graph of the change in the circulating threshold (Ct) of SARS-CoV-2 viral load in a subgroup patient; (A-B) ORF/N gene Ct values for asymptomatic and mildly infected persons, (C-D) ORF/N gene Ct values for vaccinated and unvaccinated persons.

The specific implementation mode is as follows:

the invention relates to an application of Reyanning in preparing a medicine for treating Ormcken's mild disease infection and an application of the Reyanning in preparing a medicine for improving the cycle threshold (Ct) value of an Open Reading Frame (ORF) or nucleocapsid protein (N) gene of asymptomatic infected persons. In particular, the cycle threshold (Ct value) of the Open Reading Frame (ORF) or nucleocapsid protein (N) gene of a mild infected person can be increased in a short time. The Reyanning is prepared from four medicinal materials of dandelion (372 parts), giant knotweed rhizome (372 parts), patrinia scabiosaefolia fisch.f (372 parts) and barbed skullcap herb (186 parts). The Reyanning is prepared by the following preparation method: decocting the above four materials in water twice, the first time for 2 hr, the second time for 1 hr, filtering the decoction, concentrating the filtrate under reduced pressure to appropriate amount, mixing the concentrated solutions, centrifuging, filtering, adding steviosin 1.5g and ethylparaben 0.5g, heating to boil, and making into 1000 ml.

The composition can be used for treating patients with mild SARS-CoV-2 Oncken infection. The cycle threshold (Ct value) of the Open Reading Frame (ORF) or nucleocapsid protein (N) gene of SARS-CoV-2 was detected by RT-PCR as a semiquantitative viral load for analysis. And the nucleic acid negative conversion rate, the nucleic acid negative conversion time and the hospitalization time of the mild patients and the new symptoms and the virus load of the mild patients are detected through clinical tests. The treatment effect of the mixture for treating mild infection SARS-CoV-2 Oncken patient is comprehensively evaluated. The results show that RYN improves the nucleic acid negative conversion rate, shortens the nucleic acid negative conversion time and the hospitalization time, reduces new symptoms of mild patients and reduces the virus load.

The dosage of the traditional Chinese medicine composition is as follows: the Chinese medicinal composition is administered 20ml from the first day 4 times daily for 7 days.

Experimental example:

1. study object

1) The COVID-19 asymptomatic staining diagnosis standard is met;

2) The patient is 18-80 years old, male and female are unlimited;

3) 2830 patients;

2. test drug

The experimental drug RYN is composed of dandelion, giant knotweed, dahurian patrinia herb and barbed skullcap herb, and the RYN (batch No. 220222) is produced by Qinghua de people xi' an Happy pharmaceutical Co. The product was marketed in 2005 and approved by the national drug administration (approval document: Z20050493). According to the Chinese pharmacopoeia (2020 edition), 1000ml of RYN is obtained from 372g of dandelion, 372g of giant knotweed, 372g of herba patriniae and 186g of barbed skullcap herb.

3. Method of administration

Patients meeting the conditions were randomly assigned to the intervention group (RYN + standard of care) and the control group (standard of care) according to a ratio of 1.

Patients in the intervention group were given an additional RYN cocktail (20 ml, 4 times daily) for 7 consecutive days starting on the first day of enrollment; standard care was continued to discharge after 7 days of treatment. Other concomitant medications should be documented in detail in the study. All patients received follow-up during hospitalization and were discharged within 7 days for a maximum of 7 days. If the patient needs to be transferred to a hospital for further treatment or discharged due to a worsening condition, the trial is considered complete.

4. Detection method

Collecting pharyngeal swab specimens for real-time polymerase chain reaction (RT-PCR) analysis every day from the 3 rd day of admission until nucleic acid turns negative; RT-PCR is adopted to detect the cycle threshold (Ct value) of the SARS-CoV-2 Open Reading Frame (ORF) or nucleocapsid protein (N) gene as the semi-quantitative viral load for analysis.

5. End of study

The main results of the test are the positive negative conversion time of the nucleic acid and the negative conversion rates of the nucleic acid on the 3 rd day and the 7 th day, and the secondary results comprise the hospitalization time, the disease progression proportion during the observation period and the Ct value detected by RT-PCR; the Ct value is inversely proportional to the viral load, i.e. the higher the Ct value, the lower the mRNA expression. In samples where no Ct value was detected, the Ct value was automatically set to 45 for statistical purposes. All adverse events that may or may not be associated with study drug were recorded.

The negative conversion of nucleic acid is defined as that the Ct value of N gene and ORF gene is more than or equal to 35 in two consecutive times, and the nucleic acid detection interval is at least 24 hours.

Discharge criteria were as follows: 1) Restoring the body temperature to normal for more than 3 days; 2) The respiratory symptoms are obviously improved; 3) The nucleic acid transformation is negative.

6. Statistical method

For continuous variables, normal and non-normal distribution data were analyzed using independent sample t-test and Mann-Whitney test, respectively. Normal distribution data are expressed as mean. + -. Standard deviation (mean. + -. SD). The non-normally distributed data is represented by median with quartile difference (IQR). Categorical variables are expressed in terms of frequency and percent (%) and analyzed using the chi-square test or Fisher's exact test. The time to occurrence was expressed as median and 95% Confidence Interval (CI) and analyzed using Kaplan-Meier. The changes in SARS-CoV-2 viral load during the observation period were normalized using a local regression (loess) method. Statistical analysis was performed using R software (version 4.1.3). P <0.05 is statistically significant (two-sided test).

7. Results

7.1 Baseline statistics

The study flow chart is shown in figure 1. Table 1 summarizes the baseline demographic and clinical characteristics. Among 2830 patients, 2263 patients (80.0%) had no symptom infection, and 567 patients (20.0%) had mild infection. Median age of patients enrolled was 46 years (IQR 33-56 years), 58.9% male, 41.1% female. The smallest patients are 18 years old and the largest 80 years old. The highest proportion of adult patients between 18 and 44 years of age. The most common symptoms at admission were cough (17.9%), expectoration (11.2%), fatigue (7.7%), fever (5.0%) and muscle soreness (4.7%). Hypertension (12.4%) and diabetes (3.7%) were the most common complications at baseline. 157 cases (5.5%) received antibiotic treatment, 35 cases (1.2%) received antiviral treatment, and 2 cases (0.1%) received corticosteroid treatment. Most patients were vaccinated, 2104 cases (74.3%) were vaccinated with two or more doses of vaccine. The baseline demographic and clinical profile differences between the two groups of patients were not statistically significant (P > 0.05) with the exception of the history of close contact and the history of antiviral treatment.

Table 1 baseline data and clinical characteristics.

7.2 Primary results

The median of the negative conversion time of the nucleic acids of the priming group was 7 days (IQR: 4, 10), and the median of the negative conversion time of the nucleic acids of the control group was 8 days (IQR: 6, 10.75). Kaplan-Meier analysis showed that the rate of nucleic acid negative conversion was higher in the patients receiving RYN treatment (P < 0.0001) (FIG. 2). By day 3, 81 (6.0%) of the intervention group, and 46 (3.3%) of the control group turned negative. By day 7, 727 (53.9%) patients in the intervention group were negative in nucleic acid detection, while 520 (37.5%) were negative in the control group.

The nucleic acid negative conversion rate of the patients with asymptomatic infection and mild infection in the intervention group was significantly higher than that in the control group (P < 0.05) (fig. 3).

7.3 minor results

No cases of disease progression during the observation period. Median hospital stays were 8 days in the intervention group (IQR: 5, 11) and 9 days in the control group (IQR: 7, 11). Kaplan-Meier analysis showed that patients receiving RYN treatment had a higher discharge rate (P < 0.0001) (FIG. 4).

The virus load Ct values of SARS-CoV-2ORF gene and N gene at each time point were plotted by the loess method to prepare a trend line. As shown in fig. 5, the Ct values of the patients continued to increase, and leveled off by day 9. After the Ct value reached 40, the smooth curve became stable. Ct value of ORF/N gene of dry pre-group of RYN was higher than that of control group (FIG. 5A).

As shown in FIG. 6, ct values for asymptomatic infections were higher than those with symptoms. In asymptomatic infected patients, the Ct values were higher in patients receiving RYN treatment and reached the nucleic acid negative-going criterion faster (FIG. 6A, B). As can be seen from FIGS. 6C, D, ct values were higher in vaccinated infected than in uninoculated. In addition, RYN treatment promoted nucleic acid negativity, particularly for unvaccinated patients.

7.4 conclusion

The invention provides clinical evidence for RYN to treat SARS-CoV-2 Oncken palliative infection, which indicates that RYN is a safe treatment method and is related to rapid virus elimination and disease recovery.

Compared with standard care, RYN improves the nucleic acid negative conversion rate, shortens the negative conversion time and the hospitalization time, and reduces the virus load. From the data of this study, the overall vaccination rate of the infected patients reached 78%, and nearly half (45.6%) of the patients received booster needles. In conclusion, RYN is a safe and effective therapy for treating mild Oncorks infection, and can accelerate virus elimination and promote disease recovery.

Claims (5)

1. The application of Reyanning in preparing medicine for treating infection of Ormcken's mild disease.

2. The use of thermite in the manufacture of a medicament for treating a mild-oxuker infection according to claim 1, wherein: application of Reyanning in preparing medicine for increasing Open Reading Frame (ORF) or cycle threshold (Ct) value of nucleocapsid protein (N) gene of asymptomatic infected person is provided.

3. The use of thermite according to claim 2, in the manufacture of a medicament for the treatment of the infection due to the Onckruronum, wherein: the Reyanning is prepared from water extracts of dandelion, giant knotweed rhizome, patrinia scabiosaefolia and barbed skullcap herb, wherein the weight ratio of the dandelion, the giant knotweed rhizome, the patrinia scabiosaefolia and the barbed skullcap herb is 1-3.

4. The use of thermite for the manufacture of a medicament for the treatment of a mild-to-oxkaryon infection according to claim 3, wherein: the medicine for treating the heat inflammation is prepared by the following preparation method: decocting the above four materials in water twice, the first time for 2 hr, the second time for 1 hr, filtering the decoction, concentrating the filtrate under reduced pressure to appropriate amount, mixing the concentrated solutions, centrifuging, filtering, adding steviosin 1.5g and ethylparaben 0.5g, heating to boil, and making into 1000 ml.

5. The use of thermite for the manufacture of a medicament for the treatment of a mild-to-oxkaryon infection according to claim 4, wherein: the dosage of the Reyanning is as follows: the Chinese medicinal composition is administered 20ml from the first day 4 times daily for 7 days.

Images