Traditional Chinese medicine composition for regulating intestinal flora disorder as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention discloses a traditional Chinese medicine composition for regulating intestinal flora disorder as well as a preparation method and application thereof. The traditional Chinese medicine composition is prepared from the following substances in parts by weight: 10 parts of pericarpium citri reticulatae, 10 parts of rhizoma pinellinae praeparata, 20 parts of codonopsis pilosula, 15 parts of roasted rhizoma atractylodis macrocephalae, 10 parts of fructus amomi, 20 parts of radix ophiopogonis, 20 parts of radix glehniae, 10 parts of honey-fried licorice root and 15 parts of Chinese yam. The traditional Chinese medicine composition is prepared by adopting a decoction mode according to the formula, has the effects of improving intestinal dysfunction and relieving cough of a patient after new crown infection, has a remarkable curative effect on cough and intestinal discomfort after new crown infection, can regulate intestinal flora disorder caused after new crown infection, and has a remarkable curative effect on cough and intestinal discomfort after new crown infection. The traditional Chinese medicine composition can effectively improve immunity of human bodies, especially effectively increase intestinal bacteria including bifidobacterium adolescentis, bifidobacterium longum and bifidobacterium pseudocatenuicola, is small in adverse reaction and can be used by patients for a long time.

Description

Technical Field

[0001] The present invention relates to the field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for regulating intestinal flora disorder, its preparation method and application.

Background Art

[0002] The statements in this section only provide background information related to the disclosure of the present application and may not constitute prior art.

[0003] The pandemic of coronavirus disease 2019 (COVID-19) caused by the novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) threatens global public health security. After SARS-COV-2 infection, it not only affects the lungs, but also accumulates the disorders of the gastrointestinal tract and intestinal flora and the immune status of patients. At present, there is no corresponding specific medicine for the disorders of the gastrointestinal tract and intestinal flora. Traditional Chinese medicine has achieved remarkable results in the prevention and control of the COVID-19 pandemic with its unique advantages of syndrome differentiation and treatment, multi-target intervention and regulation of intestinal flora. With the alleviation of the symptoms of the Omicron virus and the adjustment of epidemic prevention policies, the rehabilitation treatment in the post-epidemic era is particularly important.

[0004] The intestinal microecology of COVID-19 patients is abnormal, with significantly fewer beneficial bacteria and more harmful bacteria. Eubacterium rectale, Bifidobacterium adolescentis and Bifidobacterium longum are reduced. Persistent respiratory symptoms are related to opportunistic intestinal pathogens, and neuropsychiatric symptoms and fatigue are related to nosocomial intestinal pathogens, including Clostridium innocuum and Actinomyces naeslundii. Therefore, intestinal dysfunction and symptoms such as cough and qi deficiency fatigue caused by COVID-19 remission will occur.

Summary of the Invention

[0005] The purpose of the present invention is to provide a traditional Chinese medicine composition for regulating intestinal flora disorder, its preparation method and use, which can regulate intestinal dysfunction after COVID-19 infection turns negative and relieve symptoms such as cough and qi deficiency fatigue caused by COVID-19, so as to solve the problems raised in the above background art.

[0006] To achieve the above purpose, the present invention provides the following technical solutions:

[0007] On the one hand, the present application provides a traditional Chinese medicine composition for regulating intestinal flora disorder, which is made from the following raw materials in parts by weight: 10 parts of dried tangerine peel, 10 parts of pinellia ternata processed with ginger, 20 parts of codonopsis pilosula, 15 parts of stir-fried atractylodes macrocephala, 10 parts of amomum villosum, 20 parts of ophiopogon japonicus, 20 parts of glehnia littoralis, 10 parts of roasted licorice root, and 15 parts of Chinese yam. The intestinal flora disorder is the intestinal flora disorder after turning negative for novel coronavirus.

[0008] Preferably, the dosage of each part by weight is 1 g, that is, the dosage for each administration is: 10 g of dried tangerine peel, 10 g of pinellia ternata processed with ginger, 20 g of codonopsis pilosula, 15 g of stir-fried atractylodes macrocephala, 10 g of amomum villosum, 20 g of ophiopogon japonicus, 20 g of glehnia littoralis, 10 g of roasted licorice root, and 15 g of Chinese yam.

[0009] On the other hand, the present application provides a preparation method of a traditional Chinese medicine composition for regulating intestinal flora disorder, including the following steps:

[0010] Step (1): Weigh each component according to the proportion and mix them, add distilled water in an amount 5 - 10 times the total mass of the mixed raw materials, and soak for 20 - 40 min;

[0011] Step (2): Decoct for 0.5 - 1.5 h. After the decoction is completed, filter to obtain the decoction;

[0012] Step (3): Decoct again 1 - 3 times. Each time of decoction, add distilled water in an amount 3 - 10 times the total mass of the traditional Chinese medicine and decoct for 0.5 - 1.5 h;

[0013] Step (4): Combine the decoctions obtained by filtering after multiple decoctions, and perform vacuum concentration, sterilization, and then filling.

[0014] Preferably, in step (3), each time of repeated decoction is to decoct the filtered medicinal residues after adding water.

[0015] Preferably, the temperature of the decoction and repeated decoction is 90 - 100 °C.

[0016] On the other hand, the present application provides an application of a traditional Chinese medicine composition for regulating intestinal flora disorder in the preparation of a drug for regulating intestinal flora disorder after turning negative for novel coronavirus and relieving cough.

[0017] Compared with the existing technology, the beneficial effects of the present invention are:

[0018] 1. A traditional Chinese medicine composition for regulating intestinal flora disorder, its preparation method and application. Through the interaction of the components of tangerine peel, pinellia ternata processed with rhizoma zingiberis recens, codonopsis pilosula, stir-fried atractylodes macrocephala, amomum villosum, ophiopogon japonicus, glehnia littoralis, roasted licorice root, and Chinese yam, the present invention effectively increases the relative abundances of eubacterium rectale, bifidobacterium adolescentis, and bifidobacterium longum, effectively enhances human immunity, and effectively regulates intestinal function disorder after turning negative from COVID-19 infection and alleviates symptoms such as cough and qi deficiency fatigue caused by COVID-19.

[0019] 2. The present invention formulates this prescription for the population recovering after virus infection, that is, the dosage for each administration is 10 g of tangerine peel, 10 g of pinellia ternata processed with rhizoma zingiberis recens, 20 g of codonopsis pilosula, 15 g of stir-fried atractylodes macrocephala, 10 g of amomum villosum, 20 g of ophiopogon japonicus, 20 g of glehnia littoralis, 10 g of roasted licorice root, and 15 g of Chinese yam. In the prescription, pinellia ternata processed with rhizoma zingiberis recens dries dampness and resolves phlegm, lowers adverse qi and harmonizes the stomach; tangerine peel regulates qi, dries dampness and eliminates phlegm, not only assisting pinellia ternata in resolving phlegm but also making qi smooth and phlegm disappear; codonopsis pilosula, stir-fried atractylodes macrocephala, amomum villosum, and Chinese yam strengthen the spleen, replenish qi and remove dampness; ophiopogon japonicus and glehnia littoralis clear and nourish the lung and stomach, promote the production of body fluid and moisten dryness; roasted licorice root harmonizes all the medicines. The whole prescription regulates both the lung and the spleen, moistens the lung without leaving phlegm, resolves phlegm without damaging body fluid, and strengthens the spleen, removes dampness and promotes transportation. It treats both the symptoms of phlegm disturbance and the root cause of phlegm production. This composition is aimed at cough and intestinal function disorder after turning negative from COVID-19 and has the efficacy of improving intestinal function disorder and alleviating cough in patients after COVID-19 infection in clinical application.

[0020] 3. The formula of the present invention has the following advantages compared with the existing formulas: the components of the formula play a synergistic effect, the formula structure is simple, and the effect exerted is better.

Description of the Drawings

[0021] Figure 1 It is a control chart of the β diversity (NMDS) of the flora before and after treatment with the traditional Chinese medicine composition;

[0022] Figure 2 It is a control chart of the average relative abundances of the top 12 intestinal flora before and after treatment with the traditional Chinese medicine composition;

[0023] Figure 3 It is a control chart of the abundance change of eubacterium rectale before and after treatment with the traditional Chinese medicine composition;

[0024] Figure 4 It is a control chart of the abundance change of bifidobacterium longum before and after treatment with the traditional Chinese medicine composition;

[0025] Figure 5 It is a control chart of the abundance change of bifidobacterium adolescentis before and after treatment with the traditional Chinese medicine composition.

Specific Embodiments

[0026] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts belong to the scope of protection of the present invention.

[0027] In the embodiments of the present invention, to achieve the above object, the present invention provides the following technical solutions:

[0028] A traditional Chinese medicine composition for regulating intestinal flora disorder is made from the following raw materials in parts by weight: 10 parts of dried tangerine peel, 10 parts of pinellia ternata processed with rhizoma zingiberis recens, 20 parts of codonopsis pilosula, 15 parts of stir-fried atractylodes macrocephala, 10 parts of amomum villosum, 20 parts of ophiopogon japonicus, 20 parts of glehnia littoralis, 10 parts of roasted licorice root, and 15 parts of Chinese yam.

[0029] A preparation method of a traditional Chinese medicine composition for regulating intestinal flora disorder includes the following steps:

[0030] Step (1): Weigh each component according to the ratio and mix them, and add distilled water in an amount 5 times the total mass of the mixed raw materials;

[0031] Step (2): Decoct for 1 h at a temperature of 95 °C. After the decoction is completed, filter to obtain the decoction;

[0032] Step (3): Repeat the decoction of the filtered medicinal residues once. Add distilled water in an amount 5 times the total mass of the traditional Chinese medicine and decoct for 1 h at a temperature of 95 °C;

[0033] Step (4): Combine the decoctions filtered twice, and perform vacuum concentration, sterilization, and then filling.

[0034] Clinical trial methods

[0035] 1. Diagnostic criteria and inclusion criteria: All patients are convalescent patients who meet the diagnostic criteria for mild, common, and severe types of novel coronavirus infection in the "Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia"; at the same time, they are accompanied by symptoms of cough, gastrointestinal discomfort, and qi deficiency and fatigue, and meet the patients who adopt the treatment method of regulating qi and resolving phlegm, strengthening the spleen and removing dampness. Aged 18 - 40 years old, voluntarily participating in this study and being aware of the relevant clinical sampling procedures of this study.

[0036] 2. Exclusion criteria: ① Patients with severe liver and kidney function impairment; ② Pregnant or lactating patients; ③ Patients with severe underlying diseases such as diabetes, hypertension, chronic obstructive pulmonary disease, chronic bronchitis, and bronchial asthma; ④ Patients with allergic constitution or a history of allergy to the components of the research drug.

[0037] 3. Exclusion and Withdrawal Criteria: Those who did not take medicine as prescribed after inclusion, those who requested to terminate the clinical study due to personal reasons, and those who could not complete the study due to severe changes in the condition or allergic reactions.

[0038] 4. Treatment Methods: Control Group: COVID-19 recovered patients (negative antigen test or nucleic acid test), meeting the traditional Chinese medicine diagnosis of cough in the lungs, gastrointestinal discomfort, and qi deficiency fatigue, and undergoing natural recovery. Clinical samples were collected 5 - 7 days after natural recovery, and the number of included cases was 30. Treatment Group: COVID-19 recovered patients (negative antigen test or nucleic acid test), meeting the traditional Chinese medicine diagnosis of cough in the lungs, gastrointestinal discomfort, and qi deficiency fatigue, taking the health preservation and recovery formula, 2 doses per day (provided as granules by the hospital), taken once in the morning and once in the evening, and one course of treatment every 5 - 7 days. Clinical samples were collected after one course of treatment. The number of included cases was 30.

[0039] 5. Fecal microbiota detection: Using 16S detection technology, beneficial bacteria such as Faecalibacterium prausnitzii, Eubacterium rectale, Bifidobacterium adolescentis, Bifidobacterium longum, and Bifidobacterium pseudocatenulatum (intestinal bacteria lacking in the intestines of "COVID-19" patients) were used as evaluation indicators to evaluate whether the intestinal microbiota of patients after recovery was effectively restored. Intestinal microbiota detection method (Total DNA was extracted from each 250 - 500 mg fecal sample using a DNA fecal extraction kit (Qiagen, Germany). The purity and concentration of metagenomic DNA were determined using a NanoDrop 2000 spectrophotometer (Thermo Fisher Scientific, USA). Construction and sequencing: After extracting the total DNA of the sample, primers were obtained according to the design of the conserved region, and sequencing adapters were added to the ends of the primers. The microbial 16S rRNA gene was amplified using the forward primer 5’-ACTCCTACGGGAGGCAGCA-3’ and the reverse primer 5’-GGACTACHVGGGTWTCTAAT-3’. PCR amplification was performed, and the products were purified, quantified, and homogenized to form a sequencing library. The constructed library was first detected by the library, and the qualified library was sequenced using Illumina HiSeq 2500. The original image data files obtained by high-throughput sequencing (sequencing platforms such as Illumina HiSeq) were analyzed by Base Calling and converted into original sequencing read sequences (Reads), and the results were saved in the FASTQ (abbreviated as fq) file format, which contains the sequence information of the sequencing sequences (Reads) and the corresponding sequencing quality information.)

[0040] 6. Efficacy determination method: After 1 course of treatment, patients filled out the MMRC dyspnea score and the St. George's Respiratory Questionnaire through an online questionnaire.

[0041] 7. Results

[0042] MMRC dyspnea score St. George's Respiratory Questionnaire score Control group 1.567(1.000～2.000) 17.20(12.00～20.00) Treatment group 1.033(1.000～1.250)* 7.933(5.500～10.00)*

[0043] Note: Compared with the control group, *P < 0.054

[0044] Table 1 Results of MMRC dyspnea score and St. George's Respiratory Questionnaire [score, M(P25 - P75)]

[0045] It can be seen that neither the MMRC dyspnea score nor the St. George's Respiratory Questionnaire score meets the normal distribution. Non-parametric tests were used for measurement data. When comparing the control group and the treatment group, quartiles were used to reflect the distribution characteristics of the two groups, and data analysis was performed. The results showed that taking this formula effectively relieved and improved respiratory function.

[0046] Analysis of the results of 16s detection of intestinal flora: The NMDS results of β-diversity showed that there were certain differences in the flora structure between the two groups, indicating that the prepared traditional Chinese medicine composition has a certain function of regulating intestinal flora. Refer to Figure 1 .

[0047] When comparing the top 12 species in terms of relative abundance at the genus level and species level, the results showed that compared with the control group, the treatment group increased the average relative abundances of Subdoligranulum, Phascolarctobacterium, Bacteroides, Fusobacterium, Roseburia and Prevotella_9, and decreased the average relative abundances of genera such as Faecalibacterium, Megamonas, Escherichia_Shigella, and Lachnospira. Refer to Figure 2 .

[0048] Whether the relative abundances of beneficial bacteria such as Eubacterium rectale, Bifidobacterium adolescentis, and Bifidobacterium longum increased were selected as evaluation indicators. The results showed that at the species level, after taking this formula, the average relative abundances of Eubacterium rectale, Bifidobacterium adolescentis, and Bifidobacterium longum were all higher than those of the control group. Refer to Figures 3 - 5 .

[0049] Therefore, the application of this traditional Chinese medicine composition in the preparation of drugs for regulating intestinal flora disorders after turning negative for COVID-19, effectively increasing intestinal bacteria that enhance human immunity, and relieving cough is effective. The combined formula of the present invention has a significant curative effect on cough and intestinal discomfort following COVID-19 infection, can regulate the intestinal flora disorders caused by COVID-19 infection, especially effectively increase intestinal bacteria that enhance human immunity, including Bifidobacterium adolescentis, Bifidobacterium longum, and Bifidobacterium pseudocatenulatum (intestinal bacteria lacking in the intestines of "COVID-19" patients), and has few adverse reactions and can be used by patients for a long time.

[0050] It should be noted that the components in the traditional Chinese medicine composition provided by the present invention can also be configured according to the corresponding traditional Chinese medicine granules in proportion.

[0051] For those skilled in the art, it is obvious that the present invention is not limited to the details of the above exemplary embodiments, and the present invention can be implemented in other specific forms without departing from the spirit or basic characteristics of the present invention. Therefore, from any point of view, the embodiments should be regarded as exemplary and non-limiting. The scope of the present invention is defined by the appended claims rather than the above description. Therefore, all changes falling within the meaning and scope of the equivalent elements of the claims are intended to be included in the present invention.

[0052] In addition, it should be understood that although this specification is described according to embodiments, not every embodiment only contains an independent technical solution. This narrative way of the specification is only for clarity. Those skilled in the art should regard the specification as a whole, and the technical solutions in each embodiment can also be appropriately combined to form other embodiments that can be understood by those skilled in the art.

Claims

1. A Chinese medicine composition for regulating intestinal flora disorder, characterized in that: The invention is prepared from the following raw materials in parts by weight: 10 parts of dried orange peel, 10 parts of French pinellia, 20 parts of codonopsis pilosula, 15 parts of stir-fried atractylodes macrocephala, 10 parts of amomum villosum, 20 parts of ophiopogon japonicus, 20 parts of northern adenophora, 10 parts of roasted liquorice, and 15 parts of yam; The intestinal flora disorder is the intestinal flora disorder after the COVID-19 test turns negative.

2. A Chinese medicine composition for regulating intestinal flora disorder according to claim 1, characterized in that: The dosage of each serving by weight is 1g, that is, the dosage of each serving is: 10g of dried tangerine peel, 10g of French pinellia, 20g of codonopsis, 15g of stir-fried atractylodes, 10g of amomum, 20g of ophiopogon, 20g of northern adenophora, 10g of roasted liquorice, and 15g of yam.

3. A method for preparing a Chinese medicine composition for regulating intestinal flora disorder according to claim 2, characterized in that: The steps include: Step (1): weigh the components in proportion and mix them, and add distilled water in an amount of 5-10 times the total mass of the mixed raw materials; Step (2): decoct for 0.5-1.5 hours. After decoction is completed, filter and take the soup; Step (3): Repeat the decoction 1 to 3 times, adding 3 to 10 times the total weight of the Chinese medicine in distilled water and boiling for 0.5 to 1.5 hours each time; Step (4): Combine the decoctions filtered after multiple decoctions, concentrate under reduced pressure, sterilize, and then bottle.

4. The method for preparing a Chinese medicine composition for regulating intestinal flora disorder according to claim 3, characterized in that: The repeated decoction in step (3) is performed by adding water to the filtered medicinal residue for decoction.

5. The method for preparing a Chinese medicine composition for regulating intestinal flora disorder according to claim 4, characterized in that: The temperature of the decoction and repeated decoction is 90-100°C.

6. A Chinese medicine composition for regulating intestinal flora disorder according to any one of claims 1 to 5, and its use in the preparation of a medicine for regulating intestinal flora disorder and relieving cough after COVID-19 turns negative.

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