Traditional Chinese medicine compound for treating lung-kidney deficiency syndrome stable-phase chronic obstructive pulmonary disease as well as preparation method and application of traditional Chinese medicine compound

Abstract

The invention discloses a traditional Chinese medicine compound for treating lung-kidney deficiency syndrome stable-phase chronic obstructive pulmonary disease as well as a preparation method and application thereof, and belongs to the technical field of traditional Chinese medicines. The traditional Chinese medicine compound comprises the following raw material medicines: 18-22 g of codonopsis pilosula, 9-12 g of morinda officinalis, 12-16 g of radix astragali preparata, 7-11 g of atractylodes macrocephala koidz, 9-11 g of radix rehmanniae preparata, 9-12 g of semen cuscutae, 3-8 g of cassia twig, 10-15 g of salvia miltiorrhiza and 2-6 g of honey-fried ephedra. The traditional Chinese medicine decoction for treating the lung-kidney deficiency syndrome stable-phase chronic obstructive pulmonary disease is obtained by stewing the raw material medicines twice, combining the stewed liquid medicine twice and concentrating the combined liquid medicine. The traditional Chinese medicine compound disclosed by the invention has an excellent treatment effect on the stable-phase chronic obstructive pulmonary disease with the syndrome of deficiency of both lung and kidney, and has better effects of improving exercise tolerance of a patient, relieving clinical symptoms, improving life quality, reducing acute exacerbation times and improving lung functions compared with an existing medicine for treating the disease; meanwhile, the safety is excellent.

Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicine, and specifically relates to a traditional Chinese medicine compound for treating chronic obstructive pulmonary disease in the stable stage of lung and kidney deficiency syndrome, and a preparation method and application thereof. Background Art

[0002] Chronic obstructive pulmonary disease (COPD) is a common, preventable and treatable chronic respiratory disease characterized by persistent airflow obstruction and chronic respiratory symptoms. COPD is divided into an exacerbation phase and a stable phase. The COPD Global Initiative defines an exacerbation phase as an acute increase in respiratory symptoms in COPD patients, which is associated with increased local and systemic inflammation. The stable phase refers to a period in which COPD patients' symptoms such as cough, sputum and shortness of breath are stable or mild, and their condition has basically returned to the state before the exacerbation.

[0003] COPD is one of the major global public health burdens. It is estimated that there are 391.9 million COPD patients (30-79 years old) in the world in 2019, of which 68.2% are male, and more than 75% of COPD patients are expected to live in low- and middle-income countries. With the progress of population growth and aging trends, the total number and prevalence of COPD cases are likely to continue to increase.

[0004] COPD is the result of a complex, cumulative, and dynamic interaction between genes and the environment, which can cause long-term damage to the patient's lungs and / or alter their normal development or aging process. Smoking is the most important environmental risk factor for the development of COPD. Compared with non-smokers, smokers have a higher incidence of chronic respiratory symptoms and abnormal lung function, a faster annual decline in forced expiratory volume in the first second, and a higher COPD mortality rate. Exposure to biomass smoke is also closely associated with increased risk of COPD exacerbations, respiratory symptoms, hospitalization rates, and mortality. Occupational exposure to coal mines, silica-containing concrete, welding fumes, etc. not only increases the risk of COPD, but is also associated with the risk of death. Among people who never smoke, air pollution is the main known risk factor for the disease. COPD is a disease with genetic susceptibility and heterogeneity. The most relevant genetic risk factor for COPD discovered so far is the SERPINA1 gene mutation. With age, lung function will decline physiologically, and the prevalence of COPD will increase accordingly. Direct and various factors caused by lung dysplasia are also one of the risk factors for COPD.

[0005] As COPD progresses, the degree of airflow limitation gradually worsens, seriously impairing the patient's physical activity, undermining the patient's confidence in disease treatment, and affecting the patient's social and psychological state. Therefore, improving the patient's activity tolerance is a direction worth focusing on in the treatment of stable COPD. Acute exacerbation is an important event in the natural history of COPD and an important part of assessing the severity of the disease and the risk of future outcomes. It also has a negative impact on the patient's health status, comorbidities, hospitalization and readmission rates, as well as disease progression and survival. Pulmonary function tests are objective indicators for determining persistent airflow limitation. The percentage of forced expiratory volume in 1 second of the predicted value (FEV1%pred) can reflect the severity of the patient's airflow limitation. With the progression of COPD, the degree of small airway lesions increases, and FEV1%pred changes significantly. Forced vital capacity in 1 second of the predicted value (FVC%pred) reflects the ability to exhale the gas measured in the lung capacity at the fastest speed. When emphysema is obvious, this indicator will be greatly affected. The reduction of FVC%pred is closely related to aging and frequent respiratory symptoms.

[0006] Under various inducements such as infection and environmental pollution, COPD patients are prone to repeated exacerbations of their condition, leading to increased hospitalization rates, disability rates, and mortality rates, causing ordinary families to lose basic productivity, and consuming a large amount of medical resources, which has brought a heavy economic burden to individuals and society, and indirectly threatens national economic development. The inhaled preparations of bronchodilators (or combined with ICS), which currently occupy a dominant position, can relieve patients' dyspnea symptoms, alleviate the trend of declining lung function to a certain extent, and reduce the risk of disease progression. However, the side effects caused by long-term use will inevitably cause patients to have decreased compliance and negative emotions, affecting the overall treatment effect. Other expectorants / antioxidant drugs, by promoting sputum dilution and drainage, although they cannot reduce the risk of patients' exacerbations, can improve patients' symptoms of coughing and expectoration to a certain extent. Phosphodiesterase inhibitors can be used for COPD patients who have no indication for combined use of ICS and have a high risk of disease exacerbation, but their adverse reactions of gastrointestinal discomfort, weight loss, sleep disorders and headaches cannot be ignored. As one of the important global disease burdens, the treatment of COPD still faces arduous challenges, and more safe and effective means are urgently needed.

[0007] With its multi-target, multi-level and multi-faceted characteristics, traditional Chinese medicine has certain advantages in treating multi-symptom and complex chronic diseases. COPD can be described as "lung distension" and "asthma" in traditional Chinese medicine. "Lung distension" was first recorded in Huangdi Neijing. Lingshu·Distension Theory says: "Lung distension is caused by deficiency and fullness and coughing." Lingshu·Jingmai says: "The pulse of the hand taiyin of the lung is diseased when it moves, and the lung is distended and swollen and coughing." The name "lung distension" was first proposed. The Jinkui Yaolue of the Han Dynasty further clarified the name of lung distension, "Those who are short of breath and restless belong to lung distension." It is believed that the disease is located in the lungs, and the main symptoms are cough, asthma, and chest distension. COPD has a complex etiology and pathogenesis. It is generally believed that its overall pathological nature is deficiency in the root and excess in the superficial, and the main pathogenesis is deficiency and accumulation of vital energy. The original deficiency refers to the deficiency of the lung, spleen and kidney. The initial link is the deficiency of the lung, which will eventually affect the spleen and kidney; the organs are deficient and unable to function, water and dampness are accumulated, phlegm and blood stasis are generated, and they form accumulations, causing the vital energy to gradually be depleted and the accumulated damage is difficult to recover. The deficiency of the vital energy and the accumulated damage promote each other, and the cycle continues, eventually causing the fundamental damage of the yin and yang of the lung, and the disease progresses and is difficult to recover.

[0008] The TCM diagnostic criteria for COPD divide the TCM syndromes of COPD into three categories: acute exacerbation, stable stage, and combined syndromes. They are wind-cold attacking the lungs, external cold and internal fluid syndrome, phlegm-heat blocking the lungs, phlegm-dampness blocking the lungs, and phlegm covering the mind in the acute exacerbation, lung qi deficiency, lung spleen qi deficiency, lung kidney qi deficiency, and lung kidney qi and yin deficiency in the stable stage, and blood stasis in the combined syndrome. It can be seen that the syndromes of COPD in the stable stage are mostly caused by lung, spleen, and kidney qi deficiency, and may also be accompanied by phlegm and blood stasis. Based on the differences in staging and syndrome differentiation, the acute exacerbation stage is mainly based on methods of removing evil such as dispelling wind and cold, warming the lungs and resolving fluid, clearing heat and resolving phlegm, and resolving phlegm and lowering turbidity. The stable stage of COPD is mainly based on methods of strengthening the foundation and nourishing the essence such as tonifying the lung qi, cultivating the earth to produce gold, and tonifying both the lungs and kidneys, as well as promoting blood circulation and removing blood stasis.

[0009] COPD has a high morbidity and mortality rate, but due to its hidden onset, mild early symptoms, and lack of awareness among the population, missed diagnosis is common, and most COPD patients are already in moderate or even severe airflow obstruction when first diagnosed. Lung and kidney deficiency syndrome is the most common syndrome type in the stable phase of COPD, and the lung function grades of lung and kidney qi deficiency syndrome and lung and kidney qi and yin deficiency syndrome are mostly concentrated in GOLD grades 2 and 3, often accompanied by a higher risk of disease exacerbation and a worse prognosis.

[0010] Therefore, it is necessary to provide a Chinese medicine compound for treating chronic obstructive pulmonary disease in the stable stage of lung and kidney deficiency syndrome. Summary of the invention

[0011] In view of the above problems existing in the prior art, the first technical problem to be solved by the present invention is to provide a Chinese medicine compound for treating chronic obstructive pulmonary disease in the stable stage of lung and kidney deficiency syndrome. Compared with the existing drugs for treating the disease, the compound has better effects of improving patients' exercise tolerance, alleviating clinical symptoms, improving quality of life, reducing the number of acute exacerbations and improving lung function, and has excellent safety. The second technical problem to be solved by the present invention is to provide a method for preparing a Chinese medicine compound for treating chronic obstructive pulmonary disease in the stable stage of lung and kidney deficiency syndrome. The method is simple and convenient, and the prepared Chinese medicine compound has excellent therapeutic effect on chronic obstructive pulmonary disease in the stable stage of lung and kidney deficiency syndrome. The third technical problem to be solved by the present invention is to provide the use of a Chinese medicine compound in the treatment of chronic obstructive pulmonary disease in the stable stage of lung and kidney deficiency syndrome, which has excellent therapeutic effect and is safe and has no side effects.

[0012] In order to solve the above problems, the technical solution adopted by the present invention is as follows:

[0013] A traditional Chinese medicine compound for treating chronic obstructive pulmonary disease in the stable stage of lung and kidney deficiency syndrome, wherein the raw materials of the traditional Chinese medicine compound include: 18-22g of Codonopsis pilosula, 9-12g of Morinda officinalis, 12-16g of roasted Astragalus membranaceus, 7-11g of Atractylodes macrocephala, 9-11g of Rehmannia glutinosa, 9-12g of Cuscuta australis, 3-8g of Cinnamomum cassia twig, 10-15g of Salvia miltiorrhiza and 2-6g of roasted Ephedra sinica.

[0014] Furthermore, the raw material medicine is added with 8-12g of Belamcanda chinensis and 8-12g of Perilla seed.

[0015] Furthermore, the raw material medicine is added with 8-12g of honey aster and 8-12g of coltsfoot.

[0016] Furthermore, the raw material medicine is added with 8-12g of Scutellaria baicalensis and 8-12g of Morus alba bark.

[0017] Furthermore, the raw material medicine is added with 28-34g of Polygonum multiflorum and 8-12g of Semen Ziziphi Spinosae.

[0018] Furthermore, the raw material medicine is added with 8-12g of fried chicken gizzard lining and 12-16g of fried barley sprouts.

[0019] Further, the specific preparation steps are as follows:

[0020] 1) After soaking the API for 30 minutes, add water again until the liquid level is 2-3 cm higher than the API, boil over high heat, keep the boiling state for 30-40 minutes, and pour out the solution;

[0021] 2) Add water to the remaining residue from step 1) again until the liquid level is 2-3 cm higher than the residue, boil over high heat, keep the water slightly boiling for 30-40 minutes, and pour out the liquid;

[0022] 3) The medicinal solutions of step 1) and step 2) are combined and concentrated to 400 mL to obtain a Chinese medicinal decoction for treating chronic obstructive pulmonary disease in the stable stage with lung and kidney deficiency syndrome.

[0023] The preparation method of a Chinese medicinal compound for treating chronic obstructive pulmonary disease in the stable stage of lung and kidney deficiency syndrome is as follows:

[0024] 1) After soaking the API for 30 minutes, add water again until the liquid level is 2-3 cm higher than the API, boil over high heat, keep the boiling state for 30-40 minutes, and pour out the solution;

[0025] 2) Add water to the remaining residue from step 1) again until the liquid level is 2-3 cm higher than the residue, boil over high heat, keep the water slightly boiling for 30-40 minutes, and pour out the liquid;

[0026] 3) The medicinal solutions of step 1) and step 2) are combined and concentrated to 400 mL to obtain a Chinese medicinal decoction for treating chronic obstructive pulmonary disease in the stable stage with lung and kidney deficiency syndrome.

[0027] The Chinese medicine compound is used in treating chronic obstructive pulmonary disease in the stable stage with lung and kidney deficiency syndrome.

[0028] Furthermore, the method of using the Chinese medicine compound in the treatment of chronic obstructive pulmonary disease in the stable stage of lung and kidney deficiency syndrome is: 1 dose per day, divided into two times in the morning and evening, each time 200 mL, orally taken half an hour after a meal.

[0029] The present invention is composed of 9 Chinese medicines including Codonopsis pilosula, roasted Astragalus membranaceus, Morinda officinalis, Cuscuta chinensis, Rehmannia glutinosa, Atractylodes macrocephala, Cinnamomum cassiae, Salvia miltiorrhiza and roasted Ephedra sinica. Among them, Codonopsis pilosula is sweet and flat, belongs to the spleen and lung meridian, and greatly replenishes the qi of the spleen and lung. Basic research shows that Codonopsis pilosula can significantly alleviate the abnormal breathing behavior of COPD mice, reduce the levels of interleukin-1β, interleukin-6 and interleukin-8 in the bronchoalveolar lavage fluid of COPD mice, and reduce the congestion and edema caused by lung tissue inflammation to treat COPD. Codonopsis pilosula polysaccharide can inhibit T cell immune disorder of COPD rats, reduce airway inflammatory reaction and lung tissue lesions. Morinda officinalis is sweet and pungent in taste, slightly warm in nature, mainly enters the kidney meridian, warms the kidney to replenish the yang qi of the whole body, gradually replenishes the qi yang, eliminates the yin of the lung, and drives out the cold phlegm in the lung. Morinda officinalis contains multiple active ingredients such as anthraquinones, iridoids, naphthoic acid methyl esters, pentacyclic triterpenes, and sugars. Among them, Morinda officinalis polysaccharides can act on immune organs and immune-related cells, and can effectively improve the immune function of T cells. Codonopsis pilosula and Morinda officinalis are both monarch drugs, which can nourish the lungs and kidneys.

[0030] The assistant drugs include Rehmannia glutinosa, Radix Astragali, Atractylodes macrocephala, and Cuscuta chinensis. Among them, Rehmannia glutinosa is sweet and warm, and mainly enters the kidney meridian, nourishes blood and yin, and replenishes essence and fills the marrow. Studies have shown that Rehmannia glutinosa polysaccharide can increase the proliferation activity of leukocytes, inhibit Treg subsets, and enhance the body's immunity. Roasted Radix Astragali is sweet and warm, replenishes qi and raises yang, "can replenish qi and invigorate qi", and "Compendium of Materia Medica" says that it is "sweet, warm and pure yang", and can "replenish all deficiencies" and "strengthen the spleen and stomach". Roasted Radix Astragali is good at benefiting the body and strengthening the exterior, and is widely used in respiratory diseases. Clinical studies have shown that large doses of roasted Radix Astragali can significantly improve the respiratory muscle strength of COPD patients, thereby improving their prognosis. Modern pharmacological studies have shown that roasted Astragalus polysaccharide can reduce the levels of interleukin-8 and tumor necrosis factor-α in the serum of COPD rats, reduce tissue inflammation, thereby improving the lung ventilation function of COPD rats and increasing their blood oxygen saturation. Atractylodes macrocephala, sweet and warm, belongs to the spleen and stomach meridians, strengthens the spleen, dries dampness and replenishes qi, and assists the main drug Codonopsis pilosula in tonifying the spleen. The active ingredients of Atractylodes macrocephala, Atractylodes lactone 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. Pharmacological studies have shown that Atractylodes macrocephala polysaccharides can regulate tumor growth factor-β1, promote epithelial cell repair, and improve airway remodeling. Cuscuta chinensis, sweet and mild, enters the liver and kidney meridians, nourishes the liver and kidneys, and is more effective in nourishing the kidneys when combined with the main drug Morinda officinalis. Cuscuta chinensis ethanol extract can significantly improve the T lymphocyte subset ratio of rats with kidney yang deficiency, promote the expression of helper T cells, and increase the expression levels of serum immunoglobulin M and immunoglobulin G, thereby improving immune function.

[0031] Roasted ephedra promotes lung function and relieves asthma. Pharmacological studies have shown that ephedrine plays a major role in the antiasthmatic effect of ephedra, which relieves spasms and relieves asthma by relaxing bronchial smooth muscles. A certain therapeutic amount of ephedrine can also play a role in stimulating the respiratory center. Salvia miltiorrhiza promotes blood circulation and removes blood stasis, and has a wide range of pharmacological effects. It is reported that Salvia miltiorrhiza can significantly reduce the right ventricular hypertrophy index, pulmonary vascular wall thickness and lumen stenosis in rats with pulmonary hypertension, effectively inhibit the proliferation and remodeling of pulmonary small blood vessels, and improve pulmonary hypertension. Cinnamon twigs help yang and transform qi. Pharmacological studies have shown that it has a broad-spectrum antibacterial effect and can significantly inhibit inflammation. The above three flavors complement each other, making the tonic move, tonic without stagnation, and the compatibility is precise. The combination of all the medicines takes into account both the innate and acquired, and the spleen and kidney are tonic, which together play the effects of tonic lung and qi, replenishing essence and kidney, and strengthening the foundation.

[0032] Beneficial effects: Compared with the prior art, the advantages of the present invention are:

[0033] (1) The Chinese medicine compound of the present invention has an excellent therapeutic effect on chronic obstructive pulmonary disease in the stable stage of lung and kidney deficiency syndrome. Compared with existing drugs for treating the disease, it has better effects of improving patients' exercise tolerance, alleviating clinical symptoms, improving quality of life, reducing the number of acute exacerbations and improving lung function, and at the same time has excellent safety.

[0034] (2) The Chinese medicine compound of the present invention comprises Codonopsis pilosula, Morinda officinalis, roasted Astragalus membranaceus, Atractylodes macrocephala, Rehmannia glutinosa, Cuscuta australis, Cinnamomum cassia twig, Salvia miltiorrhiza and roasted Ephedra sinica, and different raw materials are added according to the different reaction symptoms of the patients, and has excellent therapeutic effect on chronic obstructive pulmonary disease in the stable stage of lung-kidney deficiency syndrome.

[0035] (3) The present invention combines the medicinal liquids obtained from the two steaming steps and then concentrates them to obtain a Chinese medicinal decoction for treating chronic obstructive pulmonary disease in the stable stage of lung and kidney deficiency syndrome. The preparation method is simple and convenient. DETAILED DESCRIPTION

[0036] The present invention is further described below in conjunction with specific embodiments.

[0037] Example 1

[0038] The preparation method of the Chinese medicinal compound for treating chronic obstructive pulmonary disease in the stable stage of lung and kidney deficiency syndrome is as follows:

[0039] 1) Soak 20g of Codonopsis pilosula, 10g of Morinda officinalis, 15g of roasted Astragalus membranaceus, 10g of Atractylodes macrocephala, 10g of Rehmannia glutinosa, 10g of Cuscuta australis, 6g of Cinnamon twig, 12g of Salvia miltiorrhiza and 4g of roasted Ephedra sinica in water for 30 minutes, then add water again until the liquid level is 2-3cm higher than the raw materials, boil over high heat, keep it at a slight boil for 30 minutes after boiling, and pour out the liquid;

[0040] 2) Add water to the remaining residue from step 1) again until the liquid level is 2-3 cm higher than the residue, boil over high heat, keep it at a slight boil for 30 minutes, and pour out the liquid;

[0041] 3) The medicinal solutions of step 1) and step 2) are combined and concentrated to 400 mL to obtain a Chinese medicinal decoction for treating chronic obstructive pulmonary disease in the stable stage with lung and kidney deficiency syndrome.

[0042] Example 2

[0043] The clinical tests of the Chinese herbal compound for the treatment of chronic obstructive pulmonary disease in the stable stage of lung and kidney deficiency syndrome are as follows:

[0044] 1. Test object

[0045] Case source: The cases in the present invention are derived from patients who visited the outpatient clinic of Jiangsu Provincial Hospital of Traditional Chinese Medicine from March 2022 to February 2024 and were diagnosed with lung and kidney deficiency syndrome in the stable stage of COPD.

[0046] Western medicine diagnostic criteria for stable COPD: formulated with reference to the "Guidelines for the Diagnosis and Treatment of Chronic Obstructive Pulmonary Disease (2021 Revised Edition)": recurrent and progressive worsening dyspnea, chronic cough and sputum, wheezing and chest tightness; onset in middle-aged and elderly people, with a history of exposure to risk factors such as smoking, large amounts of dust, occupational exposure, and repeated lower respiratory tract infections; forced expiratory volume in the first second / forced vital capacity after inhalation of bronchodilators <0.7; COPD can only be diagnosed after excluding other diseases that can cause similar symptoms. The stable stage of COPD is defined as: the patient's symptoms of cough, sputum, and shortness of breath are stable or mild, and the condition has basically returned to the state before the acute exacerbation.

[0047] Standards for differentiation of lung and kidney deficiency syndrome in stable COPD: refer to the diagnosis, staging and TCM differentiation of syndromes in the "Guidelines for TCM Diagnosis and Treatment of Chronic Obstructive Pulmonary Disease (2011 Edition)" issued by the Pulmonary Disease Professional Committee of the Internal Medicine Branch of the Chinese Association of Traditional Chinese Medicine. Main symptoms: shortness of breath, shortness of breath, and easy cold. Secondary symptoms: aversion to wind, spontaneous sweating, facial edema, chest tightness, tinnitus, soreness of waist and knees, frequent urination at night, coughing and nocturnal enuresis. Tongue and pulse: pale tongue, white tongue coating, thin pulse. The diagnosis can be confirmed if the main symptoms are present and there are more than 2 secondary symptoms (tongue and pulse are present).

[0048] Inclusion criteria: (1) meeting the Western medical diagnostic criteria for stable COPD; (2) meeting the TCM differentiation criteria for lung and kidney deficiency; (3) aged 40-80 years, with no gender restrictions; (4) able to complete all evaluations required for the invention; (5) informed consent, voluntary participation, and the process of obtaining informed consent in compliance with GCP regulations.

[0049] Exclusion criteria: (1) patients with a life expectancy of less than 12 months; (2) patients diagnosed with other respiratory diseases (such as bronchial asthma, bronchiectasis); (3) patients with worsening of condition or respiratory infection within 4 weeks before enrollment; (4) patients who had undergone lung resection; (5) patients with serious primary heart, liver, lung, kidney, blood or other serious diseases that affect their survival; (6) patients using drugs or treatments that affect the efficacy or safety assessment of the trial; (7) pregnant or lactating women; (8) patients who are unable to give fully informed consent due to intellectual or behavioral disorders; (9) patients suspected of or with a history of alcohol or drug abuse; (10) patients who are judged to be more likely to be lost to follow-up, such as those with frequent changes in work environment; (11) patients with allergic constitution or known allergy to the Chinese medicine ingredients in the present invention; (12) patients who are participating in clinical trials of other drugs or have taken other Chinese medicines one week ago.

[0050] 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 their own; (2) follow-up is difficult or the patient is lost; (3) medication compliance is poor; (4) serious adverse reactions occur and the observing physician orders the patient to withdraw.

[0051] Exclusion criteria: (1) Mistake of inclusion; (2) Misdiagnosis; (3) No data record; (4) No use of trial drugs.

[0052] 2. Test methods

[0053] (1) Grouping method: This is a prospective, open randomized controlled trial. First, 80 random numbers were generated using the MedSci medical tool (http: / / www.medsci.cn / ), with random numbers 1 to 40 being designated as the treatment group and 41 to 80 being designated as the control group. Patients who met the inclusion and exclusion criteria were randomly grouped according to the random numbers corresponding to the order of their outpatient visits.

[0054] (2) Sample size estimation: The present invention adopts a superior efficacy design with an intergroup ratio of 1:1. The sample size estimation formula can be expressed as: n = 2 [(μ 1-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 represents the corresponding unilateral boundary values ​​of 1-α and 1-β respectively), s is the standard deviation, and ε is the difference between the treatment group and the control group. Assume that the average improvement of the six-minute walking distance in the treatment group is 21m higher than that in the control group, that is, ε = 21.0; Assume that the standard deviation of the two groups is 39, that is, s = 39.0. Take α = 0.05 (unilateral), β = 0.1, then μ 1-0.05 =1.645,μ 1-0.1 =1.28. Substituting the above parameters into the formula, the total number of effective cases is about 60, and the expected dropout rate is about 10%, so the total number of cases included is planned to be 66. In order to ensure the smooth implementation of the present invention, the total number of cases included is expected to be 80, and the number of cases in the treatment group and the control group is equal, 40 cases each.

[0055] (3) Treatment methods

[0056] 1) The control group received conventional Western medicine treatment, and the treatment plan was formulated according to the recommended plans of groups A, B, C, and D in the "Guidelines for the Diagnosis and Treatment of Chronic Obstructive Pulmonary Disease (2021 Revised Edition)". Group A: a bronchodilator (short-acting or long-acting); Group B: long-acting muscarinic antagonists (LAMA) or long-acting beta2-agonist (LABA) or LAMA+LABA; Group C: LAMA or inhaled corticosteroid (ICS)+LABA; Group D: LAMA or LAMA+LABA or ICS+LABA or ICS+LABA+LAMA. The short-acting bronchodilator selected by the present invention is salbutamol sulfate inhalation aerosol (Ventolin), specification: 100μg / press*200 presses, 1-2 presses when necessary; LAMA is tiotropium bromide powder inhalation (Tianqingsule or Silihua), specification: 18μg / inhalation*30 inhalations, 1 inhalation each time, 1 time / day; tiotropium bromide spray (Silihua Resperidone), specification: 2.5μg / press*60 presses, 2 presses each time, 1 time / day. LAMA+LABA is umeclidinium bromide vilanterol inhalation powder inhalation (Olexin), specification: 62.5μg: 25μg / inhalation*30 inhalations, 1 inhalation each time, 1 time / day; indacaterol bromide inhalation powder inhalation (Jierun), specification: 110: 50μg / inhalation*30 inhalations, 1 inhalation each time, 1 time / day. ICS+LABA is budesonide formoterol inhalation powder (Symbicort Dubao), specifications: 160μg: 4.5μg*60 inhalations or 320μg: 9μg / inhalation*60 inhalations, 1 inhalation each time, 2 times / day; salmeterol fluticasone powder inhalation (Seretide), specifications: 50μg: 100μg / inhalation*60 inhalations, 1 inhalation each time, 2 times / day; ICS+LABA+LAMA is budegol aerosol (Bezeri), specifications: 160μg: 7.2μg: 4.8μg / press*120 presses, 2 presses each time, 2 times / day; flutiramev inhalation powder (Quanzaile), specifications: 100μg: 62.5μg: 25μg / inhalation*30 inhalations, 1 inhalation each time, 1 time / day. The medication was given for a total of 3 months, and all the above western medicines were provided by the Western Pharmacy of Jiangsu Provincial Hospital of Traditional Chinese Medicine.

[0057] 2) Treatment group: The treatment group was treated with the Chinese medicine compound prepared in Example 1 of the present invention in combination with conventional western medicine treatment, the compound medicine composition: 20g of Codonopsis pilosula, 10g of Morinda officinalis, 15g of roasted Astragalus, 10g of Atractylodes macrocephala, 10g of Rehmannia glutinosa, 10g of Cuscuta australis, 6g of Cinnamomum cassiae, 12g of Salvia miltiorrhiza and 4g of roasted Ephedra. All medicinal materials were provided by the Chinese medicine pharmacy of Jiangsu Provincial Hospital of Traditional Chinese Medicine and processed into decoction by the preparation department, 1 dose per day, twice a day, 200mL each time, orally taken half an hour after a meal.

[0058] If the following symptoms occur at the same time, the dosage can be adjusted according to the symptoms: if the asthma is obvious, add 10g of Belamcanda chinensis and 10g of Perilla seed; if the cough is obvious, add 10g of Aster tataricus and 10g of Coltsfoot Flos; if the sputum is yellow, add 10g of Scutellaria baicalensis and 10g of Morus alba bark; if the sleep is poor, add 30g of Polygonum multiflorum and 10g of Ziziphus jujuba seed; if the appetite is poor, add 10g of stir-fried chicken gizzard lining and 15g of stir-fried barley sprouts.

[0059] 3) One course of treatment was three months. Both groups received medication and were followed up for one course of treatment.

[0060] 3. Observation indicators

[0061] (1) General information: subject's gender, age, height, weight, smoking index (number of packs smoked per day x number of years of smoking), disease course, number of acute exacerbations, number of hospitalizations, lung function classification, use of western medicine, etc.

[0062] (2) Efficacy observation indicators

[0063] 1) 6-minute walk distance: The 6-minute walk distance was used to observe the activity endurance of COPD patients before and after treatment.

[0064] 2) mMRC score: Before and after treatment, tell the patient to mark the activity level at which they experience dyspnea. This scale is divided into 5 levels, with a total score of 0 to 4 points. The higher the score, the more severe the patient's dyspnea.

[0065] 3) CAT score: After explaining the content and scoring method of the questionnaire in detail to the patients, the CAT questionnaire survey of all patients was completed by the subjects themselves or recorded by the inventor on their behalf. After the survey was completed, the inventor would immediately collect the questionnaire and calculate the score. The CAT score includes 8 questions, each with a score of 0 to 5. The scores of each question are added together to get a total score of 0 to 40. The higher the score, the greater the impact on health and life.

[0066] 4) SGRQ scoring: All SGRQs are completed by patients themselves or recorded on their behalf after the content and scoring methods of the questionnaire are explained to the patients. No hints should be given. This questionnaire covers 3 main parts and 50 questions, and its score range is 0-100. The quality of life is negatively correlated with the scores of these questions. The higher the score, the worse the patient's health condition.

[0067] 5) Number of acute exacerbations: COPD acute exacerbation refers to the continuous aggravation of daily symptoms in a short period of time, and the need to change the routine COPD medication. It is mainly manifested by cough and wheezing in a short period of time, increased sputum volume with purulent or mucopurulent sputum, and may be accompanied by fever and other symptoms. The acute exacerbations within 3 months before the patient's enrollment and the acute exacerbations within 3 months after enrollment were recorded.

[0068] 6) Pulmonary function: The two pulmonary function tests of all included cases in the present invention were completed by the same technician in the pulmonary function room of the Department of Respiratory and Critical Care Medicine of Jiangsu Provincial Hospital of Traditional Chinese Medicine, and were strictly performed in accordance with the pulmonary function test guidelines. The main values ​​of FEV1%pred and FVC%pred before inhalation of bronchodilator (pre-bronchodilator, Pre) and FEV1%pred and FVC%pred after inhalation of bronchodilator (post-bronchodilator, Post) were recorded.

[0069] 7) TCM syndrome score: A quantitative grading standard for symptoms and signs was developed based on the main symptoms (shortness of breath, shortness of breath, and susceptibility to colds) and secondary symptoms (aversion to wind, spontaneous sweating, facial edema, chest tightness, tinnitus, soreness of waist and knees, frequent urination at night, coughing and enuresis, pale tongue, white tongue coating, and thin pulse). The main symptom score was recorded as 0, 2, 4, and 6 points for normal, mild, moderate, and severe, respectively, and the secondary symptoms were recorded as 0, 1, 2, and 3 points for normal, mild, moderate, and severe, respectively.

[0070] 8) Safety evaluation: The possible adverse reactions of the patient 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 should be recorded in detail. Among them, those that endanger the patient's life or cause the patient to be hospitalized are recorded as serious adverse reactions and the trial should be terminated. The following indicators should be checked regularly: blood routine, alanine aminotransferase, aspartate aminotransferase, urea, and creatinine.

[0071] 4. Test results

[0072] (1) Inclusion of cases: This paper included 80 patients who met the criteria, including 40 in the treatment group and 40 in the control group. During the follow-up, 2 patients in the treatment group dropped out due to voluntary discontinuation of Chinese medicine; 1 patient in the control group dropped out due to loss of follow-up. A total of 77 cases were finally included in the data analysis, including 38 in the treatment group and 39 in the control group.

[0073] (2) Comparison of baseline data

[0074] 1) Gender

[0075] In the treatment group, males accounted for 78.95% and females accounted for 21.05%; in the control group, males accounted for 89.74% and females accounted for 10.26%. There was no statistical difference in gender distribution between the two groups (χ 2 =1.71, P=0.19), as shown in Table 1 below.

[0076] Table 1 Gender distribution of treatment group and control group

[0077]

[0078]

[0079] 2) Age

[0080] The average age of patients in the treatment group was 67.34±6.82 years old, and the age of patients in the control group was 67.00±8.84 years old. There was no statistical difference in the age distribution of patients between the two groups (t=0.19, P=0.85), as shown in Table 2 below.

[0081] Table 2 Age distribution of treatment group and control group

[0082]

[0083] 3) Body mass index (BMI)

[0084] The mean BMI of the patients in the treatment group was 22.71±3.46 kg / m 2 The mean BMI of the control group was 24.01±3.35 kg / m 2 There was no statistical difference in BMI between the two groups (t=1.67, P=0.10), and they were comparable, as shown in Table 3 below.

[0085] Table 3 BMI distribution of treatment group and control group

[0086]

[0087] 4) Disease course

[0088] The median disease course of the patients in the treatment group was 5 years, and the median disease course of the patients in the control group was 6 years. There was no statistical difference in the disease course between the two groups (D=0.13, P=0.91), as shown in Table 4 below.

[0089] Table 4 Disease course of the treatment group and the control group [M(P 25 , P 75 )]

[0090]

[0091] 5) Smoking Index

[0092] The median smoking index of patients in the treatment group and the control group was 30 pack-years, and there was no statistically significant difference in the smoking index between the two groups (D=0.13, P=0.88), as shown in Table 5 below.

[0093] Table 5 Smoking status of treatment group and control group [M(P 25 , P 75 )]

[0094]

[0095] 6) Distribution of lung function grades

[0096] Among the patients in the treatment group, 7.89% had a lung function grade of GOLD1, 47.37% had a lung function grade of GOLD2, 28.95% had a lung function grade of GOLD3, and 15.79% had a lung function grade of GOLD4. In the control group, 7.69% had a lung function grade of GOLD1, 38.46% had a lung function grade of GOLD2, 43.59% had a lung function grade of GOLD3, and 10.26% had a lung function grade of GOLD4. Fisher's exact test was used to analyze the distribution of GOLD grades between the treatment group and the control group, and the groups were comparable, as shown in Table 6 below.

[0097] Table 6 Distribution of lung function grades in the treatment group and the control group

[0098]

[0099] 7) Inhalant use

[0100] The proportion of patients in the treatment group who used LAMA treatment was 7.89%, LAMA+LABA accounted for 42.11%, ICS+LABA accounted for 0.00%, and ICS+LAMA+LABA accounted for 50.00%; the proportion of patients in the control group who used LAMA treatment was 10.26%, LAMA+LABA accounted for 28.20%, ICS+LABA accounted for 5.13%, and ICS+LAMA+LABA accounted for 56.41%. Fisher's exact test was used to analyze and found that there was no statistical difference in the use of inhalers between the treatment group and the control group, as shown in Table 7 below.

[0101] Table 7 Usage of inhalers in the treatment group and the control group

[0102]

[0103] Note: LAMA: long-acting anticholinergic drug; LABA: long-acting β2 receptor agonist; ICS: inhaled corticosteroid.

[0104] 8) Concomitant cardiovascular disease

[0105] The proportion of patients with hypertension in the treatment group was 39.47%, and the proportion of patients with coronary heart disease was 21.05%. The proportion of patients with hypertension in the control group was 48.72%, and the proportion of patients with coronary heart disease was 13.16%. 2 The test analysis showed that there was no statistical difference in the distribution of hypertension and coronary heart disease between the two groups, and they were comparable, as shown in Table 8 below.

[0106] Table 8 Cardiovascular diseases in the treatment group and the control group

[0107]

[0108]

[0109] (3) Efficacy evaluation

[0110] 1) Comparison of exercise tolerance before and after treatment

[0111] Before treatment, there was no significant difference in 6MWD between the two groups of patients (P=0.96); after treatment, the 6MWD of both groups of patients was significantly improved compared with that before treatment, and the 6MWD of the treatment group was significantly better than that of the control group (D=0.35, P<0.05), as shown in Table 9 below.

[0112] Table 9 Comparison of 6MWD between the two groups of patients before and after treatment [M(P 25 , P 75 )]

[0113]

[0114] Note: Intra-group comparison before and after treatment, ** P<0.01; after treatment, the intergroup comparison # P<0.05.

[0115] 2) Comparison of mMRC scores before and after treatment

[0116] There was no statistical difference in the mMRC scores between the treatment group and the control group before treatment (P=0.23). After treatment, the mMRC scores of both groups were significantly lower than those before treatment. The mMRC score of the treatment group was significantly lower than that of the control group, and the difference was statistically significant (Z=-2.79, P<0.01), as shown in Table 10.

[0117] Table 10 Comparison of mMRC scores between the two groups [M(P 25 , P 75 )]

[0118] Grouping Sample size (cases) Before treatment (minutes) After treatment (minutes) Treatment Group 38 2.00(2.00，3.00) <![CDATA[1.00(1.00,2.00) **## ]]> Control group 39 2.00(2.00，2.00) <![CDATA[2.00(1.00,2.00) ** ]]>

[0119] Note: Intra-group comparison before and after treatment, ** P<0.01; after treatment, the intergroup comparison ## P<0.01.

[0120] 3) Comparison of CAT scores before and after treatment

[0121] There was no significant difference in CAT scores between the treatment group and the control group before treatment (P=0.36). After treatment, the CAT scores of both the treatment group and the control group were significantly improved (P<0.01). The improvement in CAT scores in the treatment group was significantly better than that in the control group, and the difference was statistically significant (t=5.88, P<0.01), as shown in Table 11.

[0122] Table 11 Comparison of the efficacy of CAT scores before and after treatment between the two groups

[0123]

[0124]

[0125] Note: Intra-group comparison before and after treatment, * P<0.01; after treatment, the intergroup comparison ## P<0.01.

[0126] 4) Comparison of SGRQ scores before and after treatment

[0127] Before treatment, there was no statistical difference in SGRQ scores between the two groups (P=0.31), and the two groups were comparable. After 3 months of treatment, the SGRQ score of the treatment group was lower than that of the control group, but the difference was not statistically significant (D=0.22, P=0.17), as shown in Table 12 below.

[0128] Table 12 Comparison of the efficacy of SGRQ scores before and after treatment between the two groups [M(P 25 , P 75 )]

[0129] Grouping Sample size (cases) Before treatment (minutes) After treatment (minutes) Treatment Group 38 38.61(34.25，40.35) <![CDATA[33.20(32.20,34.50) ** ]]> Control group 39 36.54(34.51，39.81) <![CDATA[33.63(29.07,36.51) ** ]]>

[0130] Note: Intra-group comparison before and after treatment, ** P<0.01.

[0131] 5) Comparison of the number of acute exacerbations before and after treatment

[0132] There was no statistical difference in the number of acute exacerbations before treatment between the treatment group and the control group (P = 0.36), and they were comparable. During the treatment, one case in the treatment group had an acute exacerbation, which improved after 7 days of hospitalization in the general ward; 16 cases in the control group had acute exacerbations, of which 6 were hospitalized in the general ward, 4 were treated in the outpatient department, and 6 were treated at home. After 3 months of treatment, the number of acute exacerbations in the treatment group was significantly reduced (P < 0.01), while the number of acute exacerbations in the control group was not significantly reduced (P > 0.05). The difference between the two groups was statistically significant (t = 4.5, P < 0.01), as shown in Table 13 below.

[0133] Table 13 Comparison of the number of acute exacerbations before and after treatment between the two groups

[0134] Grouping Sample size (cases) Before treatment (times) After treatment (times) Treatment Group 38 0.26±0.45 <![CDATA[0.03±0.16 **## ]]> Control group 39 0.41±0.59 0.41±0.50

[0135] Note: Intra-group comparison before and after treatment, * P<0.01; after treatment, the intergroup comparison ## P<0.01.

[0136] 6) Comparison of lung function before and after treatment

[0137] There was no significant statistical difference in Pre FEV1% pred and Post FEV1% pred between the treatment group and the control group before treatment (P=0.99; P=0.43). After 3 months of treatment, Pre FEV1% pred and Post FEV1% pred in the treatment group were both higher than before treatment, and the difference was statistically significant (P=0.02; P=0.03), while those in the control group were both lower than before treatment, but the difference was not statistically significant (P=0.11; P=0.10). After 3 months of treatment, Pre FEV1% pred in the treatment group was better than that in the control group, but the difference was not statistically significant (P=0.24), while Post FEV1% pred in the treatment group was also better than that in the control group, and the difference was statistically significant (P=0.04), as shown in Table 14 below.

[0138] Before treatment, there was no statistical difference in Pre FVC% pred and Post FVC% pred between the treatment group and the control group (P = 0.12; P = 0.24), which was comparable. After 3 months of treatment, Pre FVC% pred and Post FVC% pred in the treatment group were both higher than before treatment, and the difference was statistically significant (P < 0.01; P = 0.04), while Pre FVC% pred in the control group was lower than before, but the difference was not statistically significant (P = 0.11), while Post FVC% pred was significantly lower (P = 0.01). After treatment, Pre FVC% pred in the treatment group was significantly better than that in the control group, and the difference was statistically significant (P < 0.01); Post FVC% pred in the treatment group was better than that in the control group, but the difference was not statistically significant (P = 0.06), as shown in Table 14 below.

[0139] Table 14 Comparison of lung function between the two groups before and after treatment

[0140]

[0141] Note: Pre FEV1%pred: the percentage of the forced expiratory volume at the end of the first second before inhalation of bronchodilators; Post FEV1%pred: the percentage of the forced expiratory volume at the end of the first second after inhalation of bronchodilators; PreFVC%pred: the percentage of the forced vital capacity before inhalation of bronchodilators; Post FVC%pred: the percentage of the forced vital capacity after inhalation of bronchodilators; Intra-group comparison before and after treatment, * P<0.05; after treatment, the intergroup comparison # P<0.05; intra-group comparison before and after treatment, ** P<0.01; after treatment, the intergroup comparison ## P<0.01.

[0142] 7) Comparison of TCM syndrome scores before and after treatment

[0143] There was no statistical difference in the TCM syndrome scores between the treatment group and the control group before treatment (P=0.35), and they were comparable. After 3 months of treatment, both the treatment group and the control group were significantly reduced (P<0.01). The treatment group was significantly better than the control group, and the difference between the groups was statistically significant (P=0.01), as shown in Table 15 below.

[0144] Table 15 Comparison of TCM syndrome scores between the two groups

[0145] Grouping Sample size (cases) Before treatment (minutes) After treatment (minutes) Treatment Group 38 21.47±3.65 <![CDATA[15.50±3.17 **# ]]> Control group 39 20.69±3.61 <![CDATA[17.31±2.98 ** ]]>

[0146] Note: Intra-group comparison before and after treatment, ** P<0.01; after treatment, the intergroup comparison # P<0.05.

[0147] 8) Safety evaluation: No adverse reactions related to the treatment drugs were observed in the 77 patients in the treatment group and the control group during the treatment. No abnormal test indexes with clinical significance were found in either group after treatment. The distribution of test indexes with mild abnormalities (not clinically significant) was as follows: 1 case of elevated urea nitrogen (8.31mmol / L) and 1 case of elevated white blood cell count (10.18*10 9 In the control group, 3 cases had elevated urea nitrogen (8.68mmol / L, 8.10mmol / L, 10.66mmol / L), 1 case had elevated creatinine (118.40μmol / L), and 2 cases had elevated white blood cell counts (11.10*10 9 / L, 10.16*10 9 / L), 1 case had a decrease in the absolute value of lymphocytes (0.69*10 9 / L), and 1 case had an increase in the absolute value of neutrophils (7.74*10 9 / L). The incidence of abnormal test indicators in the treatment group was lower than that in the control group, but 2 The test showed that there was no significant statistical difference between the two groups (P>0.05), as shown in Table 16 below.

[0148] Table 16 Comparison of test indicators between the two groups

[0149]

Claims

1. A Chinese medicinal compound for treating chronic obstructive pulmonary disease in the stable stage of lung and kidney deficiency syndrome, characterized in that: The raw materials of the traditional Chinese medicine compound include: 18-22g of Codonopsis pilosula, 9-12g of Morinda officinalis, 12-16g of roasted Astragalus membranaceus, 7-11g of Atractylodes macrocephala, 9-11g of Rehmannia glutinosa, 9-12g of Cuscuta australis, 3-8g of Cinnamomum cassia twig, 10-15g of Salvia miltiorrhiza and 2-6g of roasted Ephedra sinica.

2. The Chinese medicinal compound for treating chronic obstructive pulmonary disease in the stable stage of lung and kidney deficiency syndrome according to claim 1, characterized in that: The raw material medicine is added with 8-12g of Belamcanda chinensis and 8-12g of Perilla seed.

3. The Chinese medicinal compound for treating chronic obstructive pulmonary disease in the stable stage of lung and kidney deficiency syndrome according to claim 1, characterized in that: The raw material medicine is added with 8-12g of honey aster and 8-12g of coltsfoot flower.

4. The Chinese medicinal compound for treating chronic obstructive pulmonary disease in the stable stage of lung and kidney deficiency syndrome according to claim 1, characterized in that: The raw material medicine is added with 8-12g of Scutellaria baicalensis and 8-12g of Morus alba bark.

5. The Chinese medicinal compound for treating chronic obstructive pulmonary disease in the stable stage of lung and kidney deficiency syndrome according to claim 1, characterized in that: The raw material medicine is added with 28-34g of Radix Polygoni Multiflori and 8-12g of Semen Ziziphi Spinosae.

6. The Chinese medicinal compound for treating chronic obstructive pulmonary disease in the stable stage of lung and kidney deficiency syndrome according to claim 1, characterized in that: The raw material medicine is added with 8-12g of fried chicken gizzard lining and 12-16g of fried barley sprouts.

7. The Chinese medicinal compound for treating chronic obstructive pulmonary disease in the stable stage of lung and kidney deficiency syndrome according to claim 1, characterized in that: The specific preparation steps are as follows: 1) After soaking the API for 30 minutes, add water again until the liquid level is 2-3 cm higher than the API, boil over high heat, keep the water at a slight boil for 30-40 minutes, and pour out the liquid; 2) Add water to the remaining residue from step 1) again until the liquid level is 2-3 cm higher than the residue, boil over high heat, keep the water slightly boiling for 30-40 minutes, and pour out the liquid; 3) The medicinal solutions of step 1) and step 2) are combined and concentrated to 400 mL to obtain a Chinese medicinal decoction for treating chronic obstructive pulmonary disease in the stable stage with lung and kidney deficiency syndrome.

8. A method for preparing a Chinese medicinal compound for treating chronic obstructive pulmonary disease in the stable stage of lung and kidney deficiency syndrome, characterized in that: The specific preparation steps are as follows: 1) After soaking the API for 30 minutes, add water again until the liquid level is 2-3 cm higher than the API, boil over high heat, keep the boiling state for 30-40 minutes, and pour out the solution; 2) Add water to the remaining residue from step 1) again until the liquid level is 2-3 cm higher than the residue, boil over high heat, keep the water slightly boiling for 30-40 minutes, and pour out the liquid; 3) The medicinal solutions of step 1) and step 2) are combined and concentrated to 400 mL to obtain a Chinese medicinal decoction for treating chronic obstructive pulmonary disease in the stable stage with lung and kidney deficiency syndrome.

9. Use of the Chinese medicinal compound according to claims 1 to 7 in the treatment of chronic obstructive pulmonary disease in the stable stage with deficiency of both lung and kidney.

10. The use according to claim 9, characterized in that: The method of using the Chinese medicine compound in treating chronic obstructive pulmonary disease in the stable stage of lung and kidney deficiency syndrome is: one dose per day, divided into two times in the morning and evening, each time 200 mL, orally taken half an hour after a meal.

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