Use of Sanryo-byakutsu in the manufacture of a drug to treat neuropsychiatric symptoms in patients with COVID-19 infection after recovery

Abstract

Use of Shenling Byakujutsu in the manufacture of a drug to treat neuropsychiatric symptoms in patients with COVID-19 infection after recovery.

Description

[Technical Field]

[0001] [CROSS-REFERENCE TO RELATED APPLICATIONS] This application claims priority from a Chinese patent application filed with the State Intellectual Property Office of the People's Republic of China on December 21, 2022, bearing application number 202211651746.X, the entire contents of which are incorporated herein by reference.

[0002] The present disclosure is in the field of medicine and traditional Chinese medicine, and specifically relates to the use of Shen Ling Baizhu in treating neuropsychiatric symptoms in patients with COVID-19 after recovery. [Background technology]

[0003] Shenling-baijutsusan is a representative prescription of "cultivating earth and shedding gold" that originated in the Song Dynasty Pharmacopoeia of Taiping Huimin Hezhi. In this prescription, ginseng (Radix Ginseng), white atractylodes, and poria, with the functions of strengthening the spleen, increasing the lungs, and drying dampness, are considered principal medicines; yam, lotus seeds, white flat beans, and job's kernel, with the functions of strengthening the spleen, dispelling dampness, and preventing diarrhea, are considered subordinate medicines; sand kernel, with the functions of waking up the spleen and transforming dampness, and platycodon root, with the functions of promoting the lungs, invigorating qi, and promoting ascending medicines, are all auxiliary medicines; and roasted licorice, with the functions of strengthening the spleen and harmonizing the middle, is considered an emissary medicine. The entire prescription has the functions of toning the spleen, increasing the lungs, dispelling dampness, and preventing diarrhea, and is commonly used for diseases of the lungs and spleen / stomach, accompanied by symptoms such as physical deficiency, eating less, and loose stools. Clinically used Shenling-byakutsu preparations include pills, powders, granules and capsules.

[0004] Since its outbreak, the novel coronavirus disease (Corona Virus Disease 2019, COVID-19, hereafter referred to as "COVID-19") has become a global pandemic. According to the latest real-time statistical data from the World Health Organization, as of August 30, 2022, a total of 599 million confirmed cases of COVID-19 infection worldwide had been reported, with a total of 6.467 million deaths. Although most infected individuals achieve clinical recovery, even after the acute infection phase has passed and viral nucleic acid testing has become negative, they continue to experience a range of sequelae, including weakness, cough, shortness of breath, lethargy, low-grade fever, night sweats, constipation or diarrhea, chest distress, palpitations, chronic bleeding, insomnia, anxiety or depression, sensory and motor disorders, etc.; among these, more than 20% of patients remain anxious or depressed six months after acute infection, and 26% experience insomnia (Huang C, et al. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study [J]. Lancet. 2021;397(10270):220-232). These sequelae significantly impact the quality of life of patients after recovery from COVID-19 infection, and neuropsychiatric symptoms, such as insomnia, anxiety, and depression, contribute to the prolonged psychological damage caused by COVID-19 infection. Therefore, providing clinically cured COVID-19 patients with drugs that alleviate and improve their neuropsychiatric symptoms will help them return to normal life and productive activities as soon as possible. Summary of the Invention

[0005] In response to the shortcomings of the prior art, the present disclosure provides a new medicinal use of Shenling-byakuju, a traditional Chinese medicine prescription.

[0006] In order to achieve the above technical effects, the present invention provides the following technical solutions:

[0007] Provided is a use of Shenling Baizhuang in the manufacture of a medicament for treating neuropsychiatric symptoms in patients infected with the novel coronavirus after recovery, wherein the raw material composition of the Shenling Baizhuang is ginseng, braised wheat atractylodes, poria, yam, lotus seed, braised white peas, job's kernel, sand kernel, platycodon, and licorice.

[0008] Optionally, the neuropsychiatric symptoms of the novel coronavirus-infected patient after recovery include at least one of insomnia, anxiety, and depression.

[0009] Optionally, the drug is in a clinically acceptable formulation.

[0010] Optionally, the drug is selected from an extract, a pill, a powder, a granule, a tablet, or a capsule.

[0011] The weight parts of each medicinal ingredient in the raw materials of the above-mentioned Sanryo Byakujutsu are as follows: 100 parts of ginseng, 100 parts of fried white soybean, 100 parts of turmeric, 100 parts of mountain medicine, 50 parts of lotus root, 75 parts of fried white beans, 50 parts of fried soybean, 50 parts of sand bean, 50 parts of bellflower, and 100 parts of licorice.

[0012] In this specification, the term "parts by weight" or "parts" does not refer to a unit of weight or mass, but only indicates the relative weight (mass) mixing ratio relationship between each component. Depending on the actual situation, 1 part by weight may be 1 g, 4 g, 5 g, 10 g, 1 kg, or any other weight (mass).

[0013] Clinical observations have shown that Shenling Byakujutsu Granules can effectively treat neuropsychiatric symptoms in COVID-19 patients after recovery, allowing them to return to normal life and productive activities as soon as possible. [Brief explanation of the drawings]

[0014] The present disclosure will now be further described with reference to the drawings. [Figure 1] A sample of the Self-Rating Anxiety Scale (SAS) is shown below. [Figure 2] A sample of the Self-Rating Depression Scale (SDS) is shown below. DETAILED DESCRIPTION OF THE INVENTION

[0015] The 2019 novel coronavirus (2019-nCoV) not only severely damages patients' respiratory systems during the infectious phase, but also has a significant impact on their entire biological system, causing continuous and long-term sequelae and significantly affecting their physical health and quality of life. The inventor conducted a clinical observational study on the use of Shenling Baizhuang (Shenling) and Atractylodes macrocephalus (Atractylodes macrocephalus) preparation to improve neuropsychiatric symptoms after recovery in COVID-19 patients at four hospitals in Hubei Province: Tongshan County People's Hospital, Dongfeng General Hospital of National Pharmaceutical, Xianning City Central Hospital, and Yangxin County People's Hospital. Surprisingly, after nearly a month of interventional treatment, the patients' symptoms of neuropsychiatric sequelae, such as anxiety and depression, were significantly alleviated.

[0016] The present disclosure will now be described with reference to specific examples. Those skilled in the art should understand that these examples are merely illustrative of the present disclosure and are not intended to limit the scope of the present disclosure in any way.

[0017] Unless otherwise specified, the experimental methods used in the following examples are conventional methods. Unless otherwise specified, the medicinal materials, reagents, etc. used in the following examples are all commercially available products.

[0018] Example 1: Intervention effect of Sanryo-byakutsu granules on neuropsychiatric symptoms after recovery in COVID-19 infected patients This example was conducted from September 2021 to July 2022 at Tongshan County People's Hospital, National Pharmaceutical Dongfeng General Hospital, Xianning City Central Hospital, and Yangxin County People's Hospital in Hubei Province.

[0019] 1. Distribution of cases A total of 313 subjects were enrolled in the study, 313 completed, accounting for 100% of the enrolled cases. After excluding 8 subjects whose ages were outside the 18-80 year age range, 305 subjects were included in the analysis population.

[0020] 2. General case information There were 166 men (54.43%) and 139 women (45.57%); 303 (99.34%) were Han Chinese; the mean age was 46.34 ± 14.09 years, with the smallest being 2 years and the largest being 84 years. The mean body weight was 63.41 ± 7.51 kg.

[0021] 3. Vital Signs At the time of selection, the physical signs of body temperature, respiration, blood pressure, and heart rate were basically normal, and no obvious abnormalities were found in these physical signs during the study period.

[0022] 4. Administration method The mean number of days of medication during the study period was 28.09 ± 0.88 days, with a minimum of 25 days and a maximum of 32 days, for a median of 28 days. The day before subjects began taking medication was recorded as day 0, and the first day of medication was recorded as day 1, continuing in this manner up to 28 days.

[0023] The specific administration method is to administer Shenling Byakujutsu Granules three times a day, one bag (3g / bag) per time, for 28 consecutive days. The Shenling Byakujutsu Granules are produced by Beijing Han Dian Pharmaceutical Co., Ltd., with batch numbers 211032, 211134, and 211232.

[0024] 5. Therapeutic efficacy evaluation index SAS score (self-rated anxiety scale, see Figure 1) and SDS score (self-rated depression scale, see Figure 2) were measured.

[0025] 6. Data Collection All selected subjects underwent medical examinations on days 0, 14, and 28, and symptoms were collected and scored. The data on day 0 was designated "Visit 1," the data on day 14 "Visit 2," and the data on day 28 "Visit 3." These three sets of data were statistically analyzed.

[0026] 7. Statistics and Analysis Statistical analysis was performed using SAS 9.4 (or higher version) statistical analysis software.

[0027] All statistical tests were two-sided, yielding a test statistic and corresponding P value, with P<0.05 considered to indicate statistical significance.

[0028] Quantitative data included the number of cases, mean, standard deviation, minimum, median, maximum, first quartile (Q1), third quartile (Q3), and 95% confidence interval (95% CI). Comparisons between treatment groups were performed using t-tests. Analysis of covariance was used to consider the effects of covariates. For time-series data, median survival times were described, Kaplan-Meier curves were plotted, and the log-rank test was used to compare the differences in median survival times between two groups. Cox regression analysis was used to consider the effects of center and other factors.

[0029] Qualitative data described the number of cases in each category and their percentage. Chi-squared tests and Fisher's exact probability test were used to compare enumeration data between treatment groups; Wilcoxon rank-sum tests were used to compare graded data between treatment groups. To consider the influence of centers and other factors, the CMH chi-squared test or logistic regression was used.

[0030] 8. Therapeutic effects of the intervention 8.1 SAS scale (Self-Rating Anxiety Scale) score results The results are shown in Tables 1 and 2.

[0031] [Table 1]

[0032] [Table 2]

[0033] As a result of the intervention treatment, visit 2 during the study period showed a mean decrease of 17.21±12.45 points compared to the baseline score, and visit 3 showed a mean decrease of 27.44±15.94 points compared to the baseline score. Mixed-effects model and Wilcoxon signed-rank test analysis showed that all differences were statistically significant (p<0.05), indicating that the treatment significantly reduced the SAS scale scores from baseline.

[0034] 8.2 SDS scale (Self-rating Depression Scale) score results The results are shown in Tables 3 and 4.

[0035] [Table 3]

[0036] [Table 4]

[0037] As a result of the intervention treatment, visit 2 during the study period showed a mean decrease of 17.63±11.56 points compared to the baseline score, and visit 3 showed a mean decrease of 28.34±15.58 points compared to the baseline score. Mixed-effects model and Wilcoxon signed-rank test analysis showed that all differences were statistically significant (p<0.05), indicating that the treatment significantly reduced the scores on the SDS scale from baseline.

[0038] 9. Conclusion Sanling-byakutsu can treat neuropsychiatric symptoms such as anxiety, depression, and insomnia that appear after COVID-19 patients have recovered. [Industrial Applicability]

[0039] The present application provides a use of Shenling Baizhuang in the manufacture of a medicament for treating neuropsychiatric symptoms in patients infected with the novel coronavirus after recovery, the raw material composition of which is ginseng, fried wheat atractylodes, poria, yam, lotus seed, fried white peas, job's seed, sand seed, platycodon, and licorice. The applicant has discovered that Shenling Baizhuang can treat neuropsychiatric symptoms such as anxiety, depression, and insomnia that appear in patients infected with the novel coronavirus after recovery, and has excellent industrial applicability.

Claims

1. 1. Use of Sanryo-byakutsu in the manufacture of a drug for treating neuropsychiatric symptoms in patients with COVID-19 infection after recovery, The raw material composition of the said Sanling White Atractylodes is ginseng, braised wheat white atractylodes, poria, yam, lotus seeds, braised white beans, job's seed, sand seed, platycodon, and licorice.

2. The use according to claim 1, characterized in that the neuropsychiatric symptoms of the COVID-19 patient after recovery include at least one of insomnia, anxiety, and depression.

3. 3. The use according to claim 1 or 2, characterized in that the drug is in a clinically acceptable formulation.

4. The use according to claim 3, characterized in that the drug is selected from the group consisting of decoctions, pills, powders, granules, tablets and capsules.

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