Su semi-poria cocos and orange soup for relieving high secretion of mucus in acute exacerbation stage of chronic obstructive pulmonary disease as well as preparation method and application of Su semi-poria cocos and orange soup

Abstract

The invention discloses a Su semi-poria cocos-tangerine decoction for relieving high secretion of mucus in an acute exacerbation stage of chronic obstructive pulmonary disease as well as a preparation method and application of the Su semi-poria cocos-tangerine decoction, and relates to the technical field of traditional Chinese medicine compositions. The Su semi-poria cocos and orange soup is prepared from 8-10 g of fructus perillae, 8-10 g of rhizoma pinellinae praeparata, 8-10 g of ginger processed cortex magnoliae officinalis, 8-10 g of radix peucedani, 4-6 g of fried semen brassicae, 8-10 g of fried semen raphani, 8-10 g of fried rhizoma atractylodis macrocephalae, 12-15 g of poria cocos, 4-6 g of fried pericarpium citri reticulatae and 2-3 g of cortex cinnamomi. Clinical application of the Su semi-poria cocos and tangerine decoction prepared by the invention shows that compared with a control group which is only treated by conventional western medicine, the secretion amount of mucoprotein MUC5AC is greatly reduced, traditional Chinese medicine symptom integral, CAT score and mMRC score are greatly reduced, symptoms of a patient are obviously relieved, and no adverse reaction occurs. Therefore, the Su semi-poria cocos and orange soup can relieve high secretion of mucus with the syndrome of AECOPD turbid phlegm obstructing lung and improve clinical symptoms of patients, and is good in safety.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine compositions, and particularly relates to a Subanlingju decoction for alleviating hypersecretion of mucus in AECOPD, and a preparation method and application thereof. Background Art

[0002] Chronic obstructive pulmonary disease (COPD) is a common respiratory disease characterized by persistent airflow limitation, which poses a serious threat to human health. According to the Global Initiative for COPD (GOLD), the disease is divided into an acute exacerbation phase (acute worsening of symptoms and increased inflammation) and a stable phase (stable or mild symptoms). COPD has high morbidity, disability, and mortality rates worldwide, making it one of the three major causes of death worldwide, with a particularly heavy burden in low- and middle-income countries. The disease leads to a progressive and irreversible decline in lung function, severely impacting patients' quality of life and ability to survive.

[0003] COPD results from a complex, long-term interaction between genes and environmental factors, which can cause long-term damage to a patient's lungs and / or alter their normal development or aging processes. Smoking is the most important environmental risk factor, but exposure to biomass smoke, occupational dust / chemicals, and air pollution also significantly increase the risk of illness and death. Genetic susceptibility (such as SERPINA1 gene mutations), physiological decline in lung function with aging, and lung hypoplasia are also important contributing factors.

[0004] Acute exacerbation of COPD (AECOPD) is a critical event in the course of COPD, significantly worsening the patient's health status and increasing the risk of hospitalization and mortality. A history of previous exacerbations is the primary predictor of future exacerbations. AECOPD is often triggered by infection or environmental stimuli, leading to a dramatic worsening of airway inflammation, excessive proliferation of mucus-secreting cells, and the massive production of mucins (such as MUC5AC). This increases mucus viscosity and sputum retention, which not only causes coughing and expectoration, exacerbating airway obstruction and ventilatory impairment, but also creates a breeding ground for pathogens, creating a vicious cycle of "mucus hypersecretion and amplified inflammation," significantly increasing mortality.

[0005] In Traditional Chinese Medicine (TCM), COPD is classified as a "pulmonary distension" or "asthma syndrome," with its core pathogenesis being a combination of underlying deficiency (lung, spleen, and kidney deficiency) and superficial excess (the accumulation of turbid phlegm, fluid retention, and blood stasis). Stable COPD often manifests as lung, spleen, and kidney deficiency, with treatment focusing on strengthening the underlying condition. During acute exacerbations, treatment focuses on dispelling pathogenic factors (such as resolving phlegm, expelling fluid retention, and dispersing blood stasis). AECOPD, characterized by hypersecretion of mucus, corresponds closely to the TCM syndrome of "turbid phlegm obstructing the lungs" (manifested by cough, wheezing, excessive phlegm, sticky white phlegm, a sticky mouth, a greasy white tongue coating, and a slippery pulse).

[0006] At present, Western medicine mainly relies on bronchodilators (or combined with inhaled hormones) to relieve symptoms to improve airway function in AECOPD, but it can cause palpitations, hand tremors, and even increase the risk of infection. Expectorants can also be used, but although they can improve symptoms, they cannot reduce the risk of aggravation. Methylxanthines (theophylline or aminophylline) can also be used. Currently, due to the significant adverse reactions of intravenous use of methylxanthines (theophylline or aminophylline), the GOLD report and my country's Guidelines for the Diagnosis and Treatment of Chronic Obstructive Pulmonary Disease (2021 Revised Edition) no longer recommend their use alone to treat AECOPD. Overall, the clinical treatment of AECOPD, especially the phlegm and turbidity lung syndrome characterized by mucus hypersecretion, still faces challenges, and safer and more effective intervention methods are urgently needed. Traditional Chinese medicine has unique advantages in the treatment of lung diseases based on syndrome differentiation and treatment. Research on relieving mucus hypersecretion in patients with AECOPD with phlegm and turbidity lung syndrome has important clinical value.

[0007] Professor Wei Yu, a renowned TCM expert at Jiangsu Provincial Hospital of Traditional Chinese Medicine, specializes in the diagnosis and treatment of various chronic lung diseases, particularly COPD. This application incorporates his extensive clinical experience and meticulously crafted a prescription based on the principles of strengthening the spleen and resolving phlegm, lowering qi, and relieving asthma. This prescription has been used clinically for many years and has demonstrated excellent efficacy in relieving phlegm-obstructed lungs and mucus hypersecretion in AECOPD. Summary of the Invention

[0008] In response to the aforementioned problems with the existing technology, the present application aims to provide a Subanlingju Decoction for alleviating mucus hypersecretion in AECOPD. A second technical problem addressed by the present application is to provide a method for preparing the aforementioned Subanlingju Decoction. Finally, a final technical problem addressed by the present application is to provide applications for the aforementioned Subanlingju Decoction.

[0009] In order to solve the above technical problems, the technical solutions adopted by the present invention are as follows:

[0010] A Subanlingju decoction for relieving mucus hypersecretion in acute exacerbation of chronic obstructive pulmonary disease comprises 8-10g of perilla seeds, 8-10g of French pinellia, 8-10g of ginger magnolia bark, 8-10g of peucedanum, 4-6g of stir-fried white mustard seeds, 8-10g of stir-fried radish seeds, 8-10g of stir-fried atractylodes macrocephala, 12-15g of poria, 4-6g of stir-fried tangerine peel, and 2-3g of cinnamon bark.

[0011] In some embodiments, the formula is composed of the following raw materials in parts by weight: 10g of stir-fried perilla seeds, 10g of French pinellia, 10g of ginger magnolia bark, 10g of peucedanum, 6g of stir-fried white mustard seeds, 10g of stir-fried radish seeds, 10g of stir-fried atractylodes, 15g of poria, 6g of stir-fried tangerine peel, and 3g of cinnamon.

[0012] In some embodiments, the preparation method of the Subanlingju Decoction comprises: weighing the medicinal materials according to the formula of claim 1 or 2, decocting them in water for 1-2 times, filtering, and combining the extracts.

[0013] In some embodiments, the preparation method of the Subanlingju Decoction comprises the following steps:

[0014] (1) Soak the medicinal materials in water for 30 minutes, until the liquid level covers the medicinal pieces by about 2-3 cm, boil over high heat, then keep it at a slight boil over low heat for 30-40 minutes, and pour out the first batch of medicinal liquid;

[0015] (2) Add more water until the liquid level covers the slices by about 2-3 cm, boil over high heat, then keep it at a slight boil over low heat for 30-40 minutes, and pour out the second dose of the medicine;

[0016] (3) Combine the two medicinal solutions and concentrate the solution to 400 ml by slow fire or using a vacuum rotary evaporator to obtain the Chinese medicinal decoction "Su Ban Ling Ju Tang".

[0017] The traditional Chinese medicine decoction "Subanlingjutang" is prepared by the preparation method of Subanlingjutang.

[0018] The application of the "Subanlingjutang" traditional Chinese medicine decoction in the preparation of a medicine for alleviating mucus hypersecretion in acute exacerbation of chronic obstructive pulmonary disease.

[0019] Furthermore, the dosage form of the medicine in the application is an oral dosage form.

[0020] Furthermore, the oral dosage forms of the medicine in the application include granules, tablets, capsules, oral liquids, pills, and dripping pills.

[0021] Furthermore, the medicine in the application also includes pharmaceutically acceptable excipients.

[0022] Furthermore, the excipients include lubricants, fillers, disintegrants and / or flavoring agents.

[0023] The theoretical basis for the application of Subanlingju Decoction for relieving mucus hypersecretion in AECOPD is:

[0024] According to the 2022 Jiangsu Province Traditional Chinese Medicine Predominant Disease Diagnosis and Treatment Plan, the diagnostic staging of COPD is divided into two categories: acute exacerbation and stable stage. The acute exacerbation stage includes symptoms of exterior cold and interior heat, yin deficiency and phlegm-heat, phlegm-heat stagnation in the lungs, and phlegm turbidity obstructing the lungs, respectively; the stable stage includes symptoms of lung and spleen deficiency and lung and kidney deficiency. Based on the different staging and syndrome differentiation, the stable stage syndrome is mostly characterized by lung, spleen, and kidney deficiency, with treatment focusing on tonifying and strengthening the foundation; the acute exacerbation stage focuses on dispelling pathogenic factors (such as resolving phlegm, expelling fluid, and dispersing blood stasis). The hypersecretion of mucus in AECOPD falls under the category of "phlegm turbidity obstructing the lungs" within the categories of "lung distension" and "asthma." Typical manifestations of phlegm turbidity obstructing the lungs include: primary symptoms: cough and wheezing, with copious amounts of white, sticky, or foamy sputum; secondary symptoms: chest tightness, abdominal distension, poor appetite, fatigue, and a sticky mouth; tongue coating: pale red or pale, swollen, or with tooth marks on the edges, with a greasy white or thin white coating; and a slippery or wiry pulse. These symptoms are highly consistent with the pathological state caused by hypersecretion of mucus as described in modern medicine, reflecting the consensus between Chinese and Western medicine on the nature of the same disease.

[0025] Modern pharmacological research provides theoretical evidence that the herbs in Subanlingju Decoction can improve lung function and intervene in mucus hypersecretion through multiple targets: polysaccharides in Poria cocos and Pinellia ternata can reduce MUC5AC mRNA expression in lung tissue and stabilize the Th1 / Th2 cell balance, exerting anti-inflammatory effects. Sinapine components in white mustard seeds and radish seeds can reduce inflammatory cell infiltration and mucus secretion in the lungs of asthmatic mice, reducing the expression of proinflammatory cytokines and the mucin MUC5AC mRNA. Luteolin in Perilla seeds and dried orange peel can inhibit pyroptosis and reduce lung damage in mice with acute lung injury. β-Sitosterol can inhibit type II immune responses and collagen deposition, thereby improving airway inflammation and remodeling. Imperatorin, a major chemical component in Peucedanum praeruptosae, can inhibit ROS in ARDS and affect the ROS-mediated PI3K / Akt / NF-κB signaling pathway, thereby inhibiting the production of multiple enzymes such as elastase and matrix metalloproteinases, reducing mucus secretion. The honokiol contained in Magnolia officinalis can inhibit the activation of the Notch signaling pathway of splenic T cells in COPD mice, thereby correcting the imbalance of Th1 / Th2 and Th17 / Treg cells in COPD mice, thereby improving lung function; the active ingredients of Atractylodes macrocephala, atractylodes lactones I and III, can promote changes in macrophage factors and exert anti-inflammatory effects by enhancing the expression of anti-inflammatory factors, thereby alleviating airway inflammation. Atractylodes macrocephala polysaccharides can regulate tumor growth factor-β1, promote epithelial cell repair, and improve airway remodeling; substances such as cinnamon polyphenols in cinnamon have anti-inflammatory and macrophage activation effects, and have the potential to regulate macrophage function, which can reduce inflammation and improve immune function.

[0026] Compared with the prior art, the present invention has the following advantages:

[0027] (1) Cell experiments showed that Subanlingju Decoction could significantly inhibit the expression of IL-7-induced mucin MUC5AC. In the presence of 18 mg / mL Subanlingju Decoction, the mRNA expression of MUC5AC decreased from 1.8 to 0.25, a 6.2-fold decrease compared with the 50 ng / mL IL-7 control group. At the same time, the phosphorylation of p65 and IκBα proteins was also significantly reduced. The relative expression ratio of P-P65 / P65 decreased from 1.25 to 0.5, and the relative expression ratio of P-IκBα / IκBα proteins decreased from 1.25 to 0.6. The results of cell experiments showed that Subanlingju Decoction could directly inhibit the expression of cell mucin MUC5AC gene, and could also play a role by regulating the NF-κB signaling pathway, significantly inhibiting the phosphorylation of p65 and IκBα proteins, and had great potential to relieve the symptoms of AECOPD airway inflammation and mucus hypersecretion.

[0028] (2) Clinical trials have confirmed that the observation group using Subanlingju Decoction has a more significant therapeutic effect than the control group using only conventional Western medicine:

[0029] The decrease in mucin MUC5AC secretion was greater. The secretion of mucin MUC5AC in the observation group decreased from 1.27 ng / mL before treatment to 0.64 ng / mL after treatment, while that in the control group increased from 0.60 ng / mL to 0.75 ng / mL.

[0030] The TCM symptom score of the observation group decreased from 22.60±3.72 before treatment to 8.93±2.71 after treatment, while that of the control group decreased from 19.73±4.33 to 11.60±3.54;

[0031] The CAT score of the observation group decreased from 28.67±5.19 before treatment to 14.20±5.14 after treatment, while that of the control group decreased from 26.46±7.23 to 18.87±6.91;

[0032] The number of patients with mMRC score > 2 in the observation group decreased from 14 before treatment to 1 after treatment, while the number of patients with mMRC score > 2 in the control group decreased from 11 to 0 after treatment;

[0033] The number of patients with acute exacerbations >1 within 3 months in the observation group decreased from 6 before treatment to 0 after treatment, while that in the control group decreased from 5 before treatment to 4 after treatment;

[0034] In addition, no adverse reactions were observed in either the observation group or the control group during the treatment.

[0035] Therefore, on the basis of conventional Western medicine treatment, the addition of Subanlingju Decoction can significantly improve the patient's clinical symptoms, have a better prognosis, and has a significant therapeutic effect in relieving hypersecretion of mucus. The overall clinical effect is better than that of the conventional Western medicine treatment group.

[0036] In summary, the present application is confirmed by in vitro cell experiments and clinical experiments that Su Banling Ju Decoction can relieve AECOPD phlegm turbidity lung syndrome mucus hypersecretion, improve the clinical symptoms of patients, and has good safety. BRIEF DESCRIPTION OF DRAWINGS

[0037] Figure 1 Figure 4 is a graph of the effect of different concentrations of IL-17 on 16HBE cells, wherein A is a graph of the effect of different concentrations of IL-7 on the viability of 16HBE cells; B is an immunofluorescence analysis graph of the MUC5AC protein expression effect of the different concentration IL-17 treatment group (the scale in the graph is 12.5 μm); C is a MUC5AC protein expression average fluorescence intensity graph of the different concentration IL-17 treatment group; D is the relative expression amount of MUC5AC mRNA in the different concentration IL-17 treatment group, in graphs C and D, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001;

[0038] Figure 2 Figure 5 is a graph of the effect of Su Banling Ju Decoction on the expression of MUC5AC in 16HBE cells treated by IL-17; wherein A is a graph of the viability of 16HBE cells treated by different concentrations of Su Banling Ju Decoction for 48 hours; B is an immunofluorescence analysis graph of the significant inhibition of MUC5AC expression by different concentrations of Su Banling Ju Decoction (the scale in the graph is 12.5 μm); C is a MUC5AC protein expression average fluorescence intensity graph of the different concentration Su Banling Ju Decoction treatment group; D is a graph of the relative expression amount of MUC5AC mRNA in 16HBE cells treated by different concentrations of Su Banling Ju Decoction, in graphs C and D, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001;

[0039] Figure 3 Figure 6 is a graph of the relative expression amount of P-P65 / P65 in 16HBE cells in different concentration Su Banling Ju Decoction treatment groups (*P<0.05);

[0040] Figure 4 Figure 7 is a graph of the relative expression amount of P-IκBα / IκBα in 16HBE cells in different concentration Su Banling Ju Decoction treatment groups (*P<0.05). DETAILED DESCRIPTION

[0041] To make the objects, technical solutions, and advantages of the present invention more apparent, the present invention will be further described below with reference to specific examples. Unless otherwise specified in the following examples, the technical means used are conventional means well known to those skilled in the art. Alternatively, the methods may be performed according to the kits and product instructions. Materials, reagents, etc. used in the following examples, unless otherwise specified, can be obtained from commercial sources.

[0042] Example 1

[0043] Preparation method of Subanlingju Decoction for relieving mucus hypersecretion in AECOPD (phlegm-turbid lung syndrome):

[0044] 1. Ingredients of Subanlingju Decoction: stir-fried Perilla Seed 10g, French Pinellia 10g, Magnolia Bark 10g, Peucedanum 10g, stir-fried White Mustard Seed 6g, stir-fried Radish Seed 10g, stir-fried Atractylodes 10g, Poria 15g, stir-fried Tangerine Peel 6g, and Cinnamon Bark 3g.

[0045] 2. Preparation method: A preparation method of the above-mentioned traditional Chinese medicine compound "Subanlingju Decoction" for relieving hypersecretion of mucus due to phlegm and turbidity in the lungs caused by AECOPD comprises the following steps:

[0046] (1) Soak fried perilla seeds, French pinellia, ginger magnolia bark, peucedanum chinense, fried white mustard seeds, fried radish seeds, fried atractylodes macrocephala, poria, fried tangerine peel, and cinnamon for 30 minutes;

[0047] (2) Add water to the soaked Chinese medicine until the liquid level covers the slices by about 2-3 cm, boil over high heat, then keep it at a slight boil over low heat for 30-40 minutes, and pour out the liquid;

[0048] (3) Add more water until the liquid level covers the slices by about 2-3 cm, boil over high heat, then keep it at a slight boil over low heat for 30-40 minutes, and pour out the liquid;

[0049] (4) Combine the two medicinal solutions and concentrate the solution (about 400 ml) by slow fire or using a reduced pressure rotary evaporator to obtain a Chinese herbal decoction.

[0050] 3. Medical use: Relieve the symptoms of AECOPD with phlegm and turbidity blocking the lungs and mucus hypersecretion.

[0051] Example 2

[0052] Cell experiments verified the effect of Subanlingju Decoction on mucin gene expression in cells.

[0053] 1. Drug preparation

[0054] Prepare the corresponding herbs according to the recipe of Subanlingju Decoction (all herbs are from Jiangsu Provincial Hospital of Traditional Chinese Medicine), soak the herbs in 1000 ml of water for 1 hour, then boil for 45 minutes and collect the solution. Add 500 ml of water to the residue and continue to boil for 45 minutes. Combine the two extracts, filter and concentrate them to 4.5 g / mL. Take 20 mL of 4.5 g / mL herbal solution, mix it with 20 ml PBS (phosphate buffered saline) to prepare a 2.25 g / mL solution. Take 1 mL of the solution and mix it evenly with 3.5 mL PBS, filter it with a 0.22 μm microporous membrane to obtain a 0.5 g / mL herbal solution, which is stored at -20°C for cell experiments.

[0055] 2. Chemical reagents

[0056] 16HBE cells were purchased from the Chinese Academy of Sciences (Shanghai, China). RPMI-1640 culture medium (Gibco, catalog number: C11875500BT, USA); fetal bovine serum (Viva Cell, catalog number: C04001-500, batch number: 2406069, China); human IL-17A (PeproTech, catalog number: 200-17-25UG, batch number: 092084, USA); CCK-8 (Apexbio, batch number: NO.K101842133EF5E); antibodies: anti-mucin 5AC antibody (Abcam, ab198294, USA), β-actin antibody (Proteintech, catalog number: 66009-1-1g, USA), phosphorylated p65 antibody (CST, catalog number: 3033T, USA), p65 antibody (CST, catalog number: 8242T, USA), phosphorylated IκBα antibody (CST, catalog number: 2859T, USA), IκBα antibody (CST, catalog number: 9242S, USA).

[0057] 3. Cell culture

[0058] 16HBE cells were cultured in RPMI-1640 medium containing 10% fetal bovine serum and 1% penicillin / streptomycin in a 37°C, 5% CO2 incubator.

[0059] 4. CCK-8 assay

[0060] 16-HBE cells were plated at 8 × 10 3Cells were seeded at a density of 100 cells / well in a 96-well plate and treated with a gradient of IL-17 (0, 12.5, 25, 50, and 100 ng / ml) or Subanlingju Decoction (0, 0.5625, 1.125, 2.25, 4.5, 9, 18, 36, and 72 mg / ml). After 48 hours of incubation, CCK-8 solution was added to each well and incubated for another hour. Finally, absorbance was measured at 450 nm using a microplate reader (Bio-Tek, USA).

[0061] 5. Immunofluorescence detection

[0062] After fixing with immunostaining fixative, cells were permeabilized three times (5 minutes each) with 0.3% Triton X-100 in PBS (PBST) and blocked with 10% goat serum for 60 minutes at room temperature. Cells were then incubated with primary antibody (anti-MUC5AC, 1:150) at 4°C overnight. The following day, cells were washed three times with PBST and incubated with secondary antibody (1:100) at room temperature for 60 minutes in the dark. After washing with PBST for 3 minutes, cells were stained with 4′,6-diamidino-2-phenylindole (DAPI). Finally, cells were covered with an anti-fluorescence quencher and images were captured using a fluorescence microscope (NIKON, Japan).

[0063] 6. Quantitative reverse transcription PCR (RT-qPCR)

[0064] Total RNA was extracted from cells treated with various concentrations of IL-17 or Subanlingju Decoction for 48 hours using FreeZol lysis buffer (Nanjing Vazyme Biotechnology Co., Ltd.). Total RNA was then reverse-transcribed into cDNA using a reverse transcription kit (Nanjing Vazyme Biotechnology Co., Ltd.). RT-qPCR reactions were performed using ChamQ Blue Universal SYBR qPCR Master Mix (Nanjing Novozyme Biotechnology Co., Ltd.) using cDNA as a template. The relative expression of target genes was calculated using the 2-ΔΔCt method. The primer sequences are as follows:

[0065] MUC5AC

[0066] Forward: 5′-CCACTGGTTCTATGGCAACACC-3′

[0067] Reverse: 5′-GCCGAAGTCCAGGCTGTGCG-3′

[0068] ACTIN

[0069] Forward: 5′-CACCATTGGCAATGAGCGGTTC-3′

[0070] Reverse: 5′-AGGTCTTTGCGGATGTCCACGT-3′

[0071] 7. Western blot detection

[0072] 16HBE cells were treated with various concentrations of IL-17 and Subanlingju Decoction for 48 hours. The cells were then harvested and lysed on ice for 15 minutes in RIPA lysis buffer containing a protease-phosphatase inhibitor cocktail. Protein concentration was determined using a BCA protein assay kit. A 10 mg protein sample was electrophoresed on a 10% separating gel and a 5% stacking gel and then transferred to a polyvinylidene fluoride (PVDF) membrane. After blocking with rapid blocking buffer for 60 minutes at room temperature, the membranes were incubated with the corresponding primary antibody at 4°C overnight. The next day, the membranes were washed with TBST and incubated with secondary antibodies. The membranes were then visualized and analyzed using an enhanced chemiluminescence (ECL) detection system and Image Lab software (Bio-Rad, USA).

[0073] 8. Statistical analysis

[0074] All experimental data included at least three biological replicates. Experimental data were analyzed using one-way ANOVA followed by Tukey's multiple comparison test using GraphPad Prism 9.5, and differences were considered statistically significant if P < 0.05.

[0075] 9. Experimental results

[0076] (1) Effects of different concentrations of IL-17 on MUC5AC expression in 16HBE cells

[0077] 16HBE cells were treated with different concentrations of IL-17 (0, 12.5, 25, 50, 100 ng / mL) and the cytotoxicity was detected by CCK-8 assay after 48 hours of culture. Figure 1 A), different concentrations of IL-17 had no significant effect on cell viability. Immunofluorescence analysis showed that the MUC5AC protein expression in the 50ng / mL IL-17 treatment group was better than that in the other concentrations ( Figure 1 BC). qPCR assay showed that the MUC5AC mRNA expression level was higher in the 12.5 ng / mL group, but considering its overall effectiveness, the 50 ng / mL concentration was ultimately selected for subsequent experiments ( Figure 1 D)

[0078] (2) Subanlingju Decoction inhibits IL-17-induced MUC5AC expression

[0079] 16HBE cells were treated with different concentrations of Subanlingju Decoction (abbreviated as JWSZJQF, with concentrations of 0, 0.5625, 1.125, 2.25, 4.5, 9, 18, 36, and 72 mg / mL, respectively) for 48 hours. CCK-8 assay showed that the cell viability of the 36 mg / mL and 72 mg / mL groups was significantly decreased ( Figure 2 A), therefore, 4.5, 9, and 18 mg / mL concentration groups were selected for subsequent experiments.

[0080] After 16HBE cells were treated with 50 ng / mL IL-17 for 48 hours, different concentrations of Subanlingju Decoction (4.5, 9, and 18 mg / mL) were added for intervention. Immunofluorescence analysis showed that 18 mg / mL Subanlingju Decoction significantly inhibited the expression of MUC5AC ( Figure 2 BC). Under the same conditions, qPCR was also used to detect MUC5AC mRNA expression, and the results showed a similar inhibitory trend ( Figure 2 D).

[0081] (3) Subanlingju Decoction reduces IL-17-induced MUC5AC expression by inhibiting the NF-κB pathway

[0082] Western Blot analysis was performed using the same cell treatment protocol. The results showed that compared with the control group, the relative expression levels of P-P65 / P65 and P-IκBα / IκBα proteins in 16HBE cells in the IL-17 (50 ng / mL) treatment group increased; while the Subanlingju Decoction intervention group significantly decreased the relative expression levels of the above proteins compared with the model group (P < 0.05). Figure 3 .

[0083] Phosphorylation of IκBα is a key switch for NF-κB pathway activation, leading to its degradation and the release of p65 / p50. Phosphorylation of p65 enhances its transcriptional activity and promotes its nuclear import, enabling efficient DNA binding and transcription initiation. Together, phosphorylation of both leads to full activation of the NF-κB transcription factor. Activated NF-κB (p65) directly binds to and upregulates the expression of core mucin genes, such as MUC5AC. Activated NF-κB also promotes goblet cell metaplasia and proliferation, increasing the number of mucus-secreting cells and driving a sustained inflammatory response, releasing more stimuli that maintain the phosphorylation of IκBα and p65, creating a vicious cycle of mucus hypersecretion. Therefore, phosphorylation of p65 and IκBα plays a crucial role in the pathological processes of airway inflammation and mucus hypersecretion in AECOPD. The above experimental results show that Subanlingju Decoction can directly inhibit the expression of the cell mucin MUC5AC gene, and can also exert its effect by regulating the NF-κB signaling pathway, significantly inhibiting the phosphorylation of p65 and IκBα proteins, and has great potential to relieve AECOPD airway inflammation and mucus hypersecretion symptoms.

[0084] Example 3

[0085] Clinical trial verifies the clinical efficacy of Subanlingju Decoction in relieving the symptoms of mucus hypersecretion in AECOPD patients with phlegm-turbid lung syndrome

[0086] 1. Experimental subjects

[0087] (1) Case source: The cases in this study were patients who were hospitalized in Jiangsu Provincial Hospital of Traditional Chinese Medicine between September 2023 and July 2024 and diagnosed with AECOPD with phlegm and turbidity obstructing the lungs.

[0088] (2) COPD Western medicine diagnostic criteria: Developed with reference to the "Guidelines for the Diagnosis and Treatment of Chronic Obstructive Pulmonary Disease (2021 Revised Edition)": dyspnea, chronic cough, sputum, and / or a history of exposure to COPD risk factors. After inhalation of bronchodilators, a pulmonary function test with a forced expiratory volume in one second / forced vital capacity (FEV1 / FVC) < 0.7 indicates persistent airflow limitation. COPD can only be diagnosed after excluding other diseases that can cause similar symptoms.

[0089] The key to the diagnosis of AECOPD is an acute onset clinical course, defined as a sudden worsening of respiratory symptoms beyond daily variability. The primary symptom is worsening dyspnea, often accompanied by wheezing, chest tightness, increased cough, increased sputum volume, changes in sputum color and / or viscosity, and fever. Palpitations, general malaise, insomnia, drowsiness, fatigue, depression, and unconsciousness may also occur.

[0090] (3) Syndrome differentiation criteria for AECOPD with phlegm-turbid lung obstruction: Refer to the diagnosis, staging, and TCM syndrome differentiation criteria in the International Guidelines for Clinical Practice of Traditional Chinese Medicine: Chronic Obstructive Pulmonary Disease. ① Cough or wheezing; ② White, sticky, or foamy sputum; ③ Greasy white tongue coating; ④ Slippery or stringy pulse; ⑤ Chest tightness and abdominal distension; ⑥ Greasy mouth; ⑦ Poor appetite; ⑧ Fatigue. Meet all four of ①, ②, ③, and ④, plus two of ⑤, ⑥, ⑦, and ⑧.

[0091] (4) Inclusion criteria: ① Meet the Western medical diagnostic criteria for AECOPD; ② Meet the TCM criteria for phlegm-turbidity obstructing the lungs; ③ Age 40-80 years old, no gender restrictions; ④ Can complete all assessments required for the study; ⑤ Informed consent, voluntary participation in the study, and the process of obtaining informed consent complies with the "Good Manufacturing Practice for Clinical Trials of Drugs".

[0092] (5) Exclusion criteria: ① Those with a life expectancy of less than 12 months; ② Those diagnosed with other respiratory diseases (such as bronchial asthma, bronchiectasis); ③ Those who have undergone lung resection; ④ Those with serious primary heart, liver, lung, kidney, blood or other serious diseases that affect their survival; ⑤ Those who use drugs or treatments that affect the effectiveness or safety assessment of the trial; ⑥ Pregnant or lactating women; ⑦ Those who cannot give fully informed consent due to intellectual or behavioral disorders; ⑧ Those who are suspected of or have a history of alcohol or drug abuse; ⑨ According to the researcher's judgment, there is a high possibility of loss to follow-up, such as those with frequent changes in work environment; ⑩ Those with allergic constitutions or known allergies to the Chinese herbal medicine ingredients in this study; Patients who are participating in clinical trials of other drugs or have taken other Chinese medicines in the past week.

[0093] (6) Dropout criteria: Patients who have been enrolled but have not completed treatment or clinical observation are considered to have dropped out in the following circumstances: ① The patient withdraws on his / her own initiative; ② Follow-up is difficult or lost; ③ Medication compliance is poor; ④ Serious adverse reactions occur and the observing physician orders the patient to withdraw.

[0094] (7) Exclusion criteria: ① Misadmission; ② Misdiagnosis; ③ No data record; ④ No use of the trial drug.

[0095] 2. Experimental methods

[0096] (1) Grouping method: This study was a prospective, open-label, randomized controlled trial. First, 68 random numbers were generated using the MedSci medical tool (http: / / www.medsci.cn / ). Random numbers 1 to 34 were designated as the observation group, and numbers 35 to 68 were designated as the control group. Patients who met the inclusion and exclusion criteria were randomly grouped according to the random number corresponding to the order of hospitalization time.

[0097] (2) Sample size estimation: This study adopted a superior efficacy design with an intergroup ratio of 1:1. The sample size estimation formula can be expressed as: n = 2[(μ1-α +μ 1-β )s / ε] 2 , where n is the sample size, α is the test level, β is the type II error, 1-β is the confidence level, and μ is the standard normal deviation limit (μ 1-α and μ 1-β = 1-α and 1-β, respectively), s is the standard deviation, and ε is the difference in effect between the observation and control groups. Based on previous research results, let the mean improvement in MUC5AC in the observation group be 0.53 ng / mL higher than that in the control group, i.e., ε = 0.53; let the standard deviation of the two groups be 1, i.e., s = 1. Assuming α = 0.05 (one-sided) and β = 0.1, then μ 1-0.05 =1.645, μ 1-0.1 =1.28. Substituting the above parameters into the formula, we get n≈60.89. The dropout rate is expected to be about 10%, so the total number of cases included is proposed to be 68.

[0098] (3) Treatment methods:

[0099] ① Control group: Conventional Western medicine treatment was used, with reference to the Global Strategy for the Diagnosis, Treatment and Prevention of Chronic Obstructive Pulmonary Disease (GOLD 2022), the Guidelines for the Diagnosis and Treatment of Chronic Obstructive Pulmonary Disease (2021 Revised Edition), and the Chinese Expert Consensus on the Diagnosis and Treatment of Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) (2017 Updated Edition) issued by the Expert Group on the Diagnosis and Treatment of Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

[0100] 1) Selection of treatment location

[0101] Depending on the severity of COPD exacerbation and comorbidities, outpatient or inpatient treatment may be chosen.

[0102] 2) Drug treatment

[0103] A. Bronchodilators: Short-acting β2-agonists alone or in combination with short-acting inhaled anticholinergics are recommended. Theophylline-based drugs are not recommended as first-line bronchodilators, but their combination may be considered if the patient's condition does not improve after 12 to 24 hours of treatment with β2-agonists and anticholinergics.

[0104] B. Anti-infection treatment: Suitable for patients with indications for the use of antibiotics, that is, patients who have the three main symptoms of worsening dyspnea, increased sputum volume, and purulent sputum; or patients who have purulent sputum and another main symptom; or patients who require invasive or non-invasive mechanical ventilation.

[0105] C. Glucocorticoid therapy: For patients with moderate to severe COPD exacerbations, the recommended dose is methylprednisolone 40 mg / day for 5 days. Nebulized inhaled glucocorticoids can replace or partially replace systemic glucocorticoids.

[0106] D. Other treatments, prevention and treatment of complications and comorbidities.

[0107] 3) Respiratory support

[0108] A. Controlled oxygen therapy: The goal is to maintain blood oxygen saturation between 88% and 92%.

[0109] B. High-flow nasal humidified oxygen therapy: In clinical practice, it is primarily used for patients with mild respiratory failure. Contraindications include cardiorespiratory arrest requiring emergency intubation and invasive mechanical ventilation; weak spontaneous breathing or coma; severe oxygenation impairment (PaO2 / FiO2 <100 mmHg); and moderate to severe respiratory acidosis and hypercapnia (pH <7.30).

[0110] C. Noninvasive mechanical ventilation.

[0111] D. Invasive ventilation

[0112] ②Observation group: The observation group was treated with Subanlingju Decoction in addition to the conventional Western medicine treatment adopted by the control group. The prescription composition was: stir-fried Perilla Seed 10g, French Pinellia 10g, Zingiber Officinale 10g, Peucedanum 10g, stir-fried White Mustard Seed 6g, stir-fried Radish Seed 10g, stir-fried Atractylodes 10g, Poria 15g, stir-fried Tangerine Peel 6g, and Cinnamon Bark 3g. All medicinal materials were provided by the Chinese medicine pharmacy of Jiangsu Provincial Hospital of Traditional Chinese Medicine and processed into a decoction by the preparation department (processing method is the same as the drug preparation method in Example 1). One dose was taken daily, twice a day, morning and evening, each time 200ml, orally half an hour after meals.

[0113] 3. Observation indicators

[0114] (1) General information: subject's gender, age, BMI, smoking history, disease course, heart rate, and lung function.

[0115] (2) Efficacy observation indicators

[0116] Main efficacy indicators:

[0117] 1) Mucin 5AC (MUC5AC): MUC5AC is a major component of respiratory mucus. Overexpression of MUC5AC leads to hypersecretion of mucus, which can form sputum plugs that block the airways and cause dyspnea, wheezing, and hypoxemia. MUC5AC levels were measured using the Human MUC5AC Enzyme-Linked Immunosorbent Assay Kit (Elabscience, E-EL-H2279, China).

[0118] 2) Interleukin-17 (IL-17): IL-17 can induce mucus production and goblet cell proliferation in airway epithelial cells, and stimulates mucus production in airway epithelial cells, contributing to the pathological progression of AECOPD. IL-17 levels were measured using the Human IL-17A Enzyme-Linked Immunosorbent Assay Kit (Elabscience, E-EL-H5812, China).

[0119] Secondary efficacy indicators:

[0120] 1) Length of hospitalization: The time from admission to discharge. The shorter the time, the faster the patient's condition improves.

[0121] 2) Traditional Chinese Medicine (TCM) syndrome score: A quantitative grading standard was developed for the severity of 11 TCM syndromes of AECOPD with phlegm and turbidity obstructing the lungs. The scores were divided into four levels, with scores ranging from 0 to 33, with higher scores indicating more severe conditions. (See Table 1 for details.)

[0122] Table 1 TCM syndrome score table

[0123]

[0124] 3) CAT Score: The Chronic Obstructive Pulmonary Disease Assessment Test (CAT) can be used to quantify the impact or burden of COPD on individuals in multiple dimensions. After the questionnaire content and scoring method are explained in detail to the patient, the subject completes it themselves or the researcher records it on their behalf. After the survey is completed, the researcher will immediately collect the questionnaire and calculate the score. The CAT score consists of 8 questions, each with a score of 0 to 5. The scores of each question are added together to form a total score of 0 to 40. The higher the score, the greater the impact on health and life. See Table 2 for details.

[0125] Table 2CAT score sheet

[0126]

[0127] 4) mMRC score: The modified Medical Research Council (mMRC) Dyspnea Scale is the most commonly used scale for assessing dyspnea severity. Subjects determine the activity level at which they experience dyspnea. This scale is divided into five levels, with a total score of 0 to 4. Higher scores indicate greater dyspnea severity. See Table 3 for details.

[0128] Table 3mMRC scale

[0129] Grading describe 0 Shortness of breath only during strenuous activity (such as running or climbing) 1 Shortness of breath when walking briskly on level ground or climbing a gentle hill 2 Walking slower than peers on level ground due to breathing difficulties or requiring rest 3 Stop to breathe after walking about 100 meters or a few minutes on flat ground 4 Severe breathing difficulties that prevent you from leaving the house, or shortness of breath when dressing or undressing

[0130] 5) Number of acute exacerbations within 3 months: a key indicator for assessing disease risk and prognosis in COPD patients.

[0131] 6) Safety evaluation: Possible adverse reactions of patients should be observed and recorded at each visit or follow-up after medication. If adverse reactions occur, their clinical manifestations, severity, abnormal test results and indicators, treatment methods and time, etc. should be recorded in detail. Among them, records of adverse reactions that endanger the patient's life or cause the patient to be hospitalized are serious adverse reactions, and the trial must be terminated.

[0132] 4. Experimental results

[0133] (1) Comparison of baseline data

[0134] The baseline data of the control group and observation group are shown in Table 4. Due to incomplete data and other factual factors, 38 patients were excluded, leaving 30 patients for the clinical study.

[0135] The majority of patients included were male with a history of smoking (60%), with only one patient under 60 years of age (59 years). Most patients had a disease duration of more than 10 years (73.3%). The mean (SD) heart rate in the observation and control groups was 83.87±14.37 and 91.00±17.42, respectively; the mean (SD) BMI was 22.01±4.52 and 19.47±10.68, respectively; the mean (SD) FEV1%pred was 42.64±20.29 and 43.01±18.71, respectively; and the mean (SD) FEV1 / FVC was 51.35±12.29 and 49.18±12.07, respectively. There were no statistically significant differences in baseline data between the two groups, indicating comparability.

[0136] (2) Efficacy evaluation

[0137] The efficacy indicators of the control group and the observation group before and after treatment are shown in Table 5.

[0138] Before and after treatment, the blood mucin (MUC5AC) content in the observation group was significantly lower than that before treatment, and the difference was statistically significant (P<0.05, P=0.017). However, there was no statistical difference in the blood mucin (MUC5AC) content in the control group before and after treatment (P>0.05, P=0.576).

[0139] Before and after treatment, the IL-17 content in the blood of the observation group was significantly lower than that before treatment, and the difference was statistically significant (P<0.05, P=0.009), while the IL-17 content in the blood of the control group had no statistically significant difference (P>0.05, P=0.888).

[0140] There was no statistical difference in the length of hospital stay between the two groups of patients (P>0.05, P=0.183).

[0141] There was no statistically significant difference in the TCM syndrome scores, CAT scores, and mMRC scores between the two groups before treatment (P>0.05). Compared with before treatment, the TCM syndrome scores, CAT scores, and mMRC scores of the two groups after treatment were significantly reduced, with statistically significant differences (P<0.05). Furthermore, the TCM syndrome scores and CAT scores of the observation group were significantly lower than those of the control group after treatment, with statistically significant differences (P<0.05).

[0142] The number of acute exacerbations in the observation group within 3 months after treatment was significantly lower than that before treatment, and the difference was statistically significant (P<0.05, P=0.017). There was no statistically significant difference in the number of acute exacerbations in the control group within 3 months before and after treatment (P>0.999). The number of acute exacerbations in the observation group within 3 months after treatment was significantly less than that in the control group, and the difference was statistically significant (P<0.05, P=0.042).

[0143] No adverse reactions were observed in the two groups of patients during the treatment.

[0144] It can be seen that under the premise of conventional Western medicine treatment, the addition of Subanlingju Decoction can significantly improve the patient's clinical symptoms, have a better prognosis, and has a significant therapeutic effect in relieving hypersecretion of mucus. The overall clinical effect is better than conventional Western medicine treatment, and the research results are statistically significant.

[0145] Table 4 Baseline data of subjects

[0146]

[0147] Table 5 Comparative data of efficacy

[0148]

[0149] This application uses cell-based experiments to demonstrate that Subanlingju Decoction can reduce IL-17-induced MUC5AC expression by inhibiting the NF-κB pathway. In clinical practice, the Subanlingju Decoction formula provided in this application is significantly effective for AECOPD with phlegm-turbidity obstructing the lungs. According to Traditional Chinese Medicine (TCM), the pathogenesis of COPD stems from dysfunction of the lungs, spleen, and kidneys. The phlegm-turbidity and mucus hypersecretion seen in AECOPD fall under the TCM categories of "phlegm and fluid," "phlegm turbidity," and "phlegm dampness." The spleen is the source of phlegm, while the lungs are the reservoir. When invaded by external pathogens, lung qi stagnates, the spleen fails to function properly, and fluids fail to return to normal, transforming into phlegm. Alternatively, it can be caused by both lung and spleen deficiency, with lung qi depleted and unable to transform fluids, and spleen qi deficient and unable to transport fluids. Chronic illness can affect the kidneys, which govern water. As the Suwen (Suwen) Treatise on Water and Heat states, "The kidneys are the gate to the stomach. If the gate is not properly closed, water accumulates and follows its kind." Impaired kidney qi and yang function leads to abnormal water metabolism, exacerbating phlegm and dampness, exacerbating cough and expectoration, and making phlegm profuse, thick, and difficult to cough up. This is precisely what Wang Lun stated in his Ming Dynasty Medical Miscellaneous Works: Treatise on Huatan Pills: "Phlegm is primarily water and originates from the kidneys; phlegm mobilizes dampness and is governed by the spleen." This suggests that the pathological manifestation of mucus hypersecretion is essentially the result of phlegm obstructing the airways and severely disrupting fluid metabolism, characterized by thick, heavy, and difficult-to-cough phlegm. The fundamental principles of treatment for this condition are to strengthen the spleen, dry dampness, resolve phlegm, and descend qi to calm asthma and eliminate congestion.

[0150] The Subanlingju Decoction provided by this application has fried perilla seeds in the prescription, which are warm but not dry, moist and descending, good at descending the lung qi that goes up against the flow, and eliminating the phlegm saliva that is blocked. It is the main medicine for treating phlegm-reversed cough and asthma. The pungent, warm and dry Banxia is strong, and it specifically eliminates the phlegm dampness that is glued together; Poria is flat in nature, sweet and light in taste, and enters the heart, lung, spleen and kidney meridians. It can invigorate the spleen, promote water and eliminate dampness, and is a commonly used medicine for treating phlegm-damp syndrome. It can treat both the symptoms and the root cause: treating the symptoms directly by promoting water and eliminating dampness, and treating the root cause by invigorating the spleen and replenishing the middle, restoring the water metabolism function, and preventing the regeneration of phlegm and dampness, that is, by invigorating the spleen to eliminate the source of phlegm and dampness, and promoting water to eliminate the symptoms of phlegm and dampness. The three are the main medicines in total, to take the effect of descending qi, invigorating the spleen and eliminating phlegm. Jiang Houpo is pungent, bitter and descending, and it can eliminate fullness and dryness, eliminate dampness and eliminate phlegm, and promote qi circulation and eliminate accumulation, so as to eliminate the three major causes of phlegm and dampness formation (spleen failure, qi stagnation, and wetness gathering into phlegm). Peucedanum chinense lowers Qi and dispels phlegm, and possesses a pungent and dispersing nature. While dispersing adverse effects and resolving phlegm, it also promotes lung Qi, assisting the main herb in resolving phlegm and relieving asthma while preventing turbid phlegm from clumping and becoming difficult to expel. Tangerine peel regulates Qi and strengthens the spleen, drying dampness and resolving phlegm, regulating Qi to aid in phlegm resolution while also strengthening the spleen to eliminate the source of phlegm. White mustard seeds warm the lungs and promote Qi, dissipating phlegm and stagnation, while radish seeds aid digestion, relieve stagnation, and lower Qi and eliminate phlegm. Stir-frying these two herbs mitigates their pungent and dispersing properties while increasing their ability to lower turbidity, synergistically dissolving thick phlegm in the airways. Stir-fried Atractylodes macrocephala is used to strengthen the spleen and replenish Qi, drying dampness and promoting diuresis. Combined with Poria cocos, it strengthens the transport and transformation of the central meridians, severing the source of phlegm and dampness, and providing a path for the excretion of existing phlegm and dampness. Cinnamon bark is the finishing touch to the formula, with its pungent, sweet, and intensely hot properties, entering the kidney, spleen, and heart meridians. First, it warms and nourishes the fire of the Mingmen, aiding the transformation of kidney yang to transpire fluids and prevent the internal accumulation of cold and dampness. Second, it warms and mobilizes spleen yang, synergizing with Atractylodes macrocephala and Poria cocos to enhance the ability to transport dampness. Third, it warms and unclogs the blood vessels, promoting the dissipation of pathological products of phlegm and stasis. The introduction of cinnamon embodies the classic principle that "for phlegm and fluid, warming herbs should be used to regulate them," fundamentally regulating fluid metabolism.

[0151] This prescription is based on the principle of "strengthening the spleen and resolving phlegm, descending qi and relieving asthma." It closely adheres to the pathogenesis of AECOPD, characterized by "lung failure to descend, spleen deficiency and dampness stagnation, and kidney failure to transform qi." By regulating triple-burner qi transformation, restoring fluid distribution, and dissolving clotted phlegm and turbidity, it achieves multifaceted regulation of mucus hypersecretion. This prescription embodies the TCM principle of "holistic syndrome differentiation and integrated treatment of internal organs," providing a comprehensive treatment approach for AECOPD, characterized by phlegm and turbidity obstructing the lungs.

[0152] The above description is only illustrative of the present invention and not restrictive. Those skilled in the art will understand that many modifications, changes or equivalents may be made without departing from the spirit and scope defined by the appended claims, but all of them will fall within the scope of protection of the present invention.

Claims

1. A Subanlingju decoction for relieving mucus hypersecretion in AECOPD, characterized in that: The formula consists of 8-10g of perilla seeds, 8-10g of French pinellia, 8-10g of ginger magnolia bark, 8-10g of peucedanum, 4-6g of stir-fried white mustard seeds, 8-10g of stir-fried radish seeds, 8-10g of stir-fried atractylodes, 12-15g of poria, 4-6g of stir-fried tangerine peel, and 2-3g of cinnamon.

2. The Subanlingju Decoction according to claim 1, characterized in that The formula is composed of the following raw materials in parts by weight: 10g of stir-fried perilla seeds, 10g of French pinellia, 10g of ginger magnolia bark, 10g of peucedanum, 6g of stir-fried mustard seeds, 10g of stir-fried radish seeds, 10g of stir-fried atractylodes macrocephala with bran, 15g of poria, 6g of tangerine peel, and 3g of cinnamon bark.

3. The preparation method of Subanlingju Decoction according to any one of claims 1 to 2, characterized in that: include: According to the formula of claim 1 or 2, weigh the medicinal materials, decoct them in water for 1-2 times, filter them, and combine the extracts.

4. The preparation method of Subanlingju Decoction according to claim 3, characterized in that: The specific steps include: (1) Soak the medicinal materials in water for 30 minutes, until the liquid level covers the medicinal pieces by about 2-3 cm, boil over high heat, then keep it at a slight boil over low heat for 30-40 minutes, and pour out the first batch of medicinal liquid; (2) Add more water until the liquid level covers the slices by about 2-3 cm, boil over high heat, then keep it at a slight boil over low heat for 30-40 minutes, and pour out the second dose of the medicine; (3) Combine the two medicinal solutions and concentrate the solution to 400 ml by slow fire or using a vacuum rotary evaporator to obtain the "Su Ban Ling Ju Tang" Chinese medicinal decoction.

5. The Chinese medicinal decoction "Subanlingjutang" prepared by the preparation method of Subanlingjutang according to claim 3 or 4.

6. Use of the traditional Chinese medicine decoction "Subanlingjutang" according to claim 5 in the preparation of a medicament for alleviating mucus hypersecretion in AECOPD.

7. The use according to claim 6, characterized in that The dosage form of the medicine in the application is an oral dosage form.

8. The use according to claim 7, characterized in that The oral dosage forms of the medicine in the application include granules, tablets, capsules, oral liquids, pills, and dripping pills.

9. The use according to claim 6, characterized in that The medicine in the application also includes pharmaceutically acceptable excipients.

10. The use according to claim 9, characterized in that The excipients include lubricants, fillers, disintegrants and / or flavoring agents.

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