Traditional Chinese medicine composition for treating or / and adjunctively treating chronic obstructive pulmonary disease as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention provides a traditional Chinese medicine composition for treating or / and adjunctively treating chronic obstructive pulmonary disease as well as a preparation method and application thereof, and belongs to the field of traditional Chinese medicines. The traditional Chinese medicine composition is prepared from the following raw material medicines in parts by weight: 12-18 parts of herba ardisiae japonicae, 12-18 parts of semen lepidii, 8-12 parts of almond, 8-12 parts of platycodon grandiflorum, 8-12 parts of blackberry lily, 8-12 parts of fructus aurantii, 12-18 parts of rhizoma pinellinae praeparata, 12-18 parts of thunberg fritillary bulb, 12-18 parts of inula flower, 12-18 parts of cynanchum glaucescens, 12-18 parts of radix stemonae, 8-12 parts of radix salviae miltiorrhizae and 4-6 parts of liquorice. The invention further provides a preparation method and application of the traditional Chinese medicine composition. According to years of clinical experience of the inventor, the prescription is checked and affirmed in a large number of COPD cases, the curative effect is obvious, the symptoms such as cough, expectoration, wheeze and shortness of breath of the chronic obstructive pulmonary disease patients can be obviously and rapidly improved, and the safety is good.

Description

Technical Field

[0001] This invention relates to a traditional Chinese medicine composition for treating and / or adjuvantly treating chronic obstructive pulmonary disease, its preparation method and uses, and belongs to the field of traditional Chinese medicine. Background Technology

[0002] Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease characterized by persistent airflow limitation, with high rates of disability and mortality. Its pathological changes mainly include chronic airway inflammation, mucus hypersecretion, airway remodeling, and lung parenchymal destruction. Globally, the incidence and disease burden of COPD remain high, seriously endangering public health. Currently, modern medicine's clinical treatment of COPD mainly relies on bronchodilators (such as β2-receptor agonists and anticholinergic drugs) and inhaled corticosteroids. While these therapies can alleviate symptoms and improve lung function to some extent, they have the following limitations: 1) Primarily symptomatic treatment: focusing mainly on airway dilation and symptom relief, with limited reversal of disease progression; 2) Significant side effects: long-term use may lead to adverse reactions such as palpitations, muscle tremors, oral fungal infections, and osteoporosis; 3) Drug resistance: some patients experience decreased responsiveness after long-term use. In traditional Chinese medicine, COPD is often categorized under "lung distension," "asthma," and "phlegm retention." Traditional Chinese medicine (TCM) theory holds that the core pathogenesis lies in the deficiency of the lung, spleen, and kidney as the root cause, while phlegm, blood stasis, and qi stagnation obstructing lung qi are the manifestations, belonging to a syndrome of deficiency in the root and excess in the manifestation, and a mixed syndrome of deficiency and excess. TCM differentiation can be roughly divided into six types: wind-cold binding the lungs, phlegm-heat obstructing the lungs, phlegm-turbidity obstructing the lungs, yang deficiency with water retention, lung and kidney qi deficiency, and lung and spleen qi deficiency (Meng Cuidi, Research Progress on the Correlation between TCM Differentiation and Laboratory Indicators in Chronic Obstructive Pulmonary Disease, Chinese Community Physician, Medical Professional, 2012, No. 2).

[0003] Many currently available traditional Chinese medicine (TCM) compound prescriptions primarily employ treatment principles such as "clearing heat and resolving phlegm," "promoting lung function and relieving asthma," or "tonifying the lungs, spleen, and kidneys." However, existing technical solutions suffer from the following shortcomings: 1) Emphasis on a single treatment principle: Most prescriptions tend to focus on clearing heat and resolving phlegm, warming and resolving cold phlegm, or tonifying deficiency. They lack a systematic and synergistic approach that addresses the complex and critical combined pathogenesis of "phlegm-heat obstructing the lungs" and "prolonged illness leading to blood stasis" commonly found in the acute or chronic phases of COPD. 2) Lack of focus on the core pathogenesis, resulting in a generalized and mixed treatment approach: Most prescriptions include both acute phase treatments such as relieving cough and resolving phlegm, and promoting blood circulation and removing blood stasis, as well as tonifying the lungs, strengthening the spleen, and nourishing yin. While the treatment is comprehensive, it fails to grasp the core pathogenesis and focus on addressing the core issues, violating the principle of treating the symptoms in acute cases and the root cause in chronic cases, leading to generally poor clinical efficacy. 3) Single therapeutic target: Some formulas excel at relieving cough and asthma, but lack specificity in improving pulmonary microcirculation and reversing airway remodeling, and are insufficiently interventional in the core pathological aspects of COPD. 4) Insufficient innovation: Some compound formulas are simply modifications of classic formulas, lacking unique concepts in drug combinations tailored to the modern pathophysiological characteristics of COPD and significant evidence of synergistic effects. Therefore, there is an urgent clinical need for a new traditional Chinese medicine regimen that can rapidly relieve the core symptoms of cough, sputum, and asthma in COPD patients, target the underlying pathology of phlegm and blood stasis, possess multi-target regulatory effects, and have higher safety.

[0004] Patent CN101843840A, invention title: A traditional Chinese medicine compound granule for treating acute exacerbations of chronic obstructive pulmonary disease. The disclosed formula contains nine traditional Chinese medicines: Lepidium seed, earthworm, Fritillaria thunbergii, prepared rhubarb, prepared ephedra, red peony root, dandelion tea, ginseng, Ophiopogon japonicus, and Acorus tatarinowii. Lepidium seed clears lung heat, relieves asthma, and promotes urination to eliminate phlegm and damp-heat obstructing the lungs; earthworm clears lung heat, promotes lung function, and relieves asthma. Together, these two herbs clear heat, eliminate phlegm, promote qi circulation, relieve asthma, and unblock the meridians, serving as the principal herbs. Ephedra is pungent, bitter, and warming, and when combined with earthworm, it enhances the effect of clearing lung heat and relieving asthma. Prepared rhubarb has a relatively mild purgative effect. The formula treats upper body ailments by addressing lower body ailments. It combines Lepidium seed with other herbs to clear phlegm from the lungs, allowing the phlegm and heat in the lung meridian to be expelled through the large intestine, the organ of the Taiyin lung. Red peony root clears heat, cools the blood, and invigorates blood circulation; Fritillaria thunbergii clears heat, resolves phlegm, and disperses nodules; Dioscorea opposita stops cough, eliminates phlegm, invigorates blood, and removes blood stasis. In this formula, processed ephedra, prepared rhubarb, Fritillaria cirrhosa, red peony root, and Dioscorea opposita are used as assistant herbs. Sun-dried ginseng tonifies qi, nourishes yin, and benefits the spleen and lungs; Ophiopogon japonicus clears the lungs, nourishes yin, and moistens dryness. These two herbs are used as adjuvant herbs. Acorus tatarinowii is pungent, bitter, dry, warm, and aromatic, and it also resolves phlegm and turbidity. It is used as the guiding herb. This invention targets the syndrome of phlegm-heat obstructing the lungs or phlegm-heat obstructing the lungs combined with blood stasis during acute exacerbations of COPD. Although it focuses on clearing heat, eliminating phlegm, promoting blood circulation, and relieving cough and asthma, the overall effect of the formula in relieving cough, eliminating phlegm, and relieving asthma is relatively weak. The research subjects included were mainly patients with mild to moderate COPD, and the clinically common severe patients were not included, which further reduces its generalizability. Moreover, the acute exacerbation of COPD is mainly characterized by phlegm and blood stasis obstruction and lung qi stagnation. According to the TCM principle of treating the symptoms in acute exacerbations and treating the root cause in chronic exacerbations, the ingredients in this formula, such as ginseng and ophiopogon japonicus, which are qi-tonifying, yin-nourishing, and righteous qi-supporting, have the disadvantage of closing the door to let the enemy escape, which is not conducive to the clearance of phlegm and blood stasis and other yin pathological products during acute exacerbations. Summary of the Invention

[0005] Based on this, the present invention aims to provide a traditional Chinese medicine composition for treating COPD based on a comprehensive treatment method of "ventilating the lungs and relieving adverse flow of qi, stopping cough and relieving asthma, clearing heat and resolving phlegm, and promoting blood circulation and unblocking collaterals", which addresses both the symptoms and the root cause, has a definite curative effect and few side effects.

[0006] This invention provides a traditional Chinese medicine composition for treating and / or adjunctive treating chronic obstructive pulmonary disease, which is prepared from the following raw materials in the indicated weight ratios:

[0007] 12-18 parts of Dwarf Tea, 12-18 parts of Lepidium Seed, 8-12 parts of Apricot Kernel, 8-12 parts of Platycodon Root, 8-12 parts of Belamcanda Rhizome, 8-12 parts of Bitter Orange Peel, 12-18 parts of Prepared Pinellia Rhizome, 12-18 parts of Fritillaria Bulb, 12-18 parts of Inula Flower, 12-18 parts of Cynanchum Root, 12-18 parts of Stemona Root, 8-12 parts of Salvia miltiorrhiza, and 4-6 parts of Licorice Root.

[0008] Preferably, it is prepared from the following raw materials in the indicated weight ratios:

[0009] 15 parts of Ardisiae Japonicae Herba, 15 parts of Lepidii Semen, 10 parts of Armeniacae Semen Amarum, 10 parts of Platycodonis Radix, 10 parts of Belamcandae Rhizoma, 10 parts of Aurantii Fructus Immaturus, 15 parts of Pinelliae Rhizoma Praeparatum, 15 parts of Thunbergii Bulbus, 15 parts of Inulae Flos, 15 parts of Cynanchi Stauntonii Radix et Rhizoma, 15 parts of Stemonae Radix, 10 parts of Salviae Miltiorrhizae Radix, 5 parts of Glycyrrhizae Radix et Rhizoma.

[0010] The traditional Chinese medicine composition of the present invention takes the crude drug powder of the raw materials or the extract with water or organic solvent as the active ingredient, and is prepared into a commonly used oral preparation in pharmacy by adding pharmaceutically acceptable excipients or auxiliary ingredients.

[0011] Among them, the oral preparation is oral liquid, tablet, capsule, pill, granule, oral liquid.

[0012] The present invention provides a preparation method of a traditional Chinese medicine composition for treating and / or assisting in treating chronic obstructive pulmonary disease, which comprises the following steps:

[0013] a. Weigh the raw materials according to each weight ratio;

[0014] b. Powder the raw materials, extract them with water or organic solvent, and then add pharmaceutically acceptable excipients or auxiliary ingredients to prepare a commonly used oral preparation in pharmacy.

[0015] Use of the traditional Chinese medicine composition described in the present invention in the preparation of a drug for treating chronic obstructive pulmonary disease.

[0016] Among them, the drug is for treating the acute exacerbation stage of chronic obstructive pulmonary disease.

[0017] The drug is for treating chronic obstructive pulmonary disease with syndrome of phlegm-heat congesting the lung and blood stasis.

[0018] The drug has the functions of dispersing the lung qi to relieve the adverse qi, relieving cough and asthma, clearing away heat and resolving phlegm, activating blood circulation and dredging collaterals.

[0019] The formula of the traditional Chinese medicine composition of the present invention takes "dispersing the lung qi to relieve the adverse qi, relieving cough and asthma, resolving phlegm and activating blood circulation" as the treatment principle, aiming at the common "phlegm, heat, stasis, congestion" core pathogenesis in the acute attack stage or remission stage of COPD (chronic obstructive pulmonary disease), and mainly treating COPD with syndrome of phlegm-heat congesting the lung and blood stasis. The formula is rigorous and the logic is clear.

[0020] The specific analysis of the formula of the traditional Chinese medicine composition in this application is as follows:

[0021] King drugs: Ardisiae Japonicae Herba, Lepidii Semen. Ardisiae Japonicae Herba is an important drug for resolving phlegm, relieving cough and asthma, and can also clear away damp-heat and promote blood circulation to remove stasis. With multiple effects in one drug, it can not only resolve the "phlegm" and "asthma" of COPD, but also target its common "blood stasis" pathology, and is very suitable as the king drug. Lepidii Semen purges the lung to relieve asthma and promotes diuresis to alleviate edema, specifically purging the qi blockage caused by phlegm and water congestion in the lung, with strong power and specific effect, aiming at the core symptoms of COPD such as wheezing with profuse phlegm and fullness and distension in the chest and hypochondrium. Compatible with Ardisiae Japonicae Herba, one resolves and the other purges, and they are both king drugs, strongly opening the airway.

[0022] The accompanying herbs are: apricot kernel, platycodon root, and belamcanda chinensis. These three herbs work together to form a "dispersing, descending, and purging" qi-regulating combination. Apricot kernel, bitter and descending, lowers lung qi to relieve asthma and cough; platycodon root, pungent and bitter, disperses and drains, opening up lung qi to expel phlegm and pus; belamcanda chinensis clears heat and detoxifies, eliminates phlegm and soothes the throat; prepared pinellia tuber and fritillaria thunbergii form a "drying and clearing" phlegm-resolving combination. Prepared pinellia tuber dries dampness, resolves phlegm, and relieves nausea and vomiting, targeting damp phlegm. Fritillaria thunbergii clears heat, resolves phlegm, and relieves stagnation, targeting hot phlegm and stubborn phlegm. The combination of these two herbs balances cold and warm properties, enhancing the phlegm-resolving effect.

[0023] The adjuvant herbs are Inula japonica, Cynanchum paniculatum, and Stemona japonica. These three herbs are specifically designed to "lower qi, resolve phlegm, stop cough, and relieve asthma." Inula japonica lowers qi, resolves phlegm, stops cough, and relieves asthma, and is especially effective in treating phlegm accumulation and qi stagnation. Cynanchum paniculatum excels at lowering qi and resolving phlegm, and can be used regardless of whether the condition is due to cold or heat. Stemona japonica moistens the lungs, lowers qi, stops cough, and kills parasites, and is effective for chronic and stubborn coughs. These three herbs enhance the effects of lowering qi, resolving phlegm, and stopping cough. Salvia miltiorrhiza: The key ingredient in this formula. COPD is a protracted disease, and "prolonged illness inevitably leads to blood stasis." Patients generally experience pulmonary microcirculatory disturbances and a hypercoagulable state. Salvia miltiorrhiza invigorates blood, removes blood stasis, unblocks meridians, and relieves pain, improving the circulation of qi and blood in the lungs. This aligns with modern medical understanding of COPD pathology and embodies the advanced TCM treatment principle of "treating phlegm and blood stasis simultaneously."

[0024] The guiding herb, licorice, harmonizes the properties of the other herbs, moistens the lungs and relieves cough, and moderates the harshness of the herbs (such as Lepidium apetalum), making the whole formula more balanced.

[0025] The entire formula uses *Eriocaulon buergerianum* and *Lepidium apetalum* as its vanguard to purge the lungs, eliminate phlegm, and relieve cough and asthma. *Prunus armeniaca*, *Platycodon grandiflorus*, and *Belamcanda chinensis* regulate the physiological functions of lung qi circulation. *Pinellia ternata*, *Fritillaria cirrhosa*, *Inula japonica*, *Cynanchum paniculatum*, and *Stemona japonica* form a powerful phlegm-resolving and cough-relieving team. *Salvia miltiorrhiza* penetrates deep into the blood to resolve blood stasis caused by prolonged illness. Finally, licorice root harmonizes the formula. This formulation embodies the treatment principle of "combining circulation and phlegm-resolving, removing blood stasis, relieving cough and asthma," closely addressing the core pathogenesis of COPD—"phlegm obstructing the airways, lung qi rising upwards, and blood stasis in the collaterals due to prolonged illness"—making it a clinically effective prescription with complete theoretical principles, methods, formula, and medication.

[0026] Compared with patent CN101843840A, Ai Ting Heji not only has a strong effect of lowering qi and relieving asthma, but also contains a variety of expectorant and antitussive herbs such as Pinellia ternata, Fritillaria thunbergii, Inula japonica, Cynanchum paniculatum, Platycodon grandiflorus, Dioscorea opposita, and Stemona japonica, forming a powerful expectorant and antitussive synergy. It is highly targeted for symptoms of cough and excessive phlegm, and its expectorant and antitussive effects are significantly better than the patent prescription. At the same time, Ai Ting Heji focuses on eliminating pathogens and does not contain any tonifying herbs, making it more suitable for the acute exacerbation of COPD, which is characterized by "phlegm and blood stasis, and impaired lung function" as the main contradiction. The clinical manifestations are characterized by severe cough, thick yellow phlegm, chest tightness and shortness of breath, but the body's vital energy is still relatively good. The prescription in this patent document uses ginseng to replenish vital energy and ophiopogon japonicus to nourish lung yin, aiming to invigorate qi and nourish yin, and strengthen the root cause. It is more suitable for the chronic persistent stage or relative remission stage of COPD, which belongs to the complex syndrome of "phlegm-heat stagnation and qi and yin deficiency". In addition to cough, wheezing and yellow phlegm, clinical manifestations are often accompanied by shortness of breath, fatigue, wheezing on exertion, dry mouth, cyanosis of the lips and dark tongue, or constipation, etc., which are mixed signs of deficiency and excess. Therefore, the Ai Ting compound focuses on treating the symptoms in acute cases, especially suitable for the acute exacerbation of COPD. In contrast, the drug of this invention combines attack and tonification, with a milder effect, focusing on the chronic stage or remission stage. The prescription ideas and effects of the two are significantly different.

[0027] The beneficial effects of this invention are:

[0028] This invention is based on years of clinical experience by the inventors' team and has been tested and confirmed in numerous COPD cases, demonstrating significant efficacy. Besides significantly and rapidly improving symptoms such as cough, sputum production, wheezing, and shortness of breath in COPD patients, it also exhibits good safety. Mechanistic studies show that this formula can significantly improve lung function in a rat model of COPD, reduce inflammatory cell infiltration in lung tissue, ciliary and alveolar destruction, and airway abnormalities, and decrease the level of inflammatory factors in bronchoalveolar lavage fluid. Attached Figure Description

[0029] Figure 1 Pathological changes in rat lung tissue. Detailed Implementation

[0030] Example 1 Preparation of the traditional Chinese medicine composition of the present invention (hereinafter referred to as "Dwarf Lepidium Compound")

[0031] The formula consists of: 15g of *Eriocaulon buergerianum*, 15g of *Lepidium apetalum*, 10g of apricot kernel, 10g of platycodon grandiflorus, 10g of *Belamcanda chinensis*, 10g of immature bitter orange, 15g of prepared pinellia ternata, 15g of fritillaria thunbergii, 15g of inula japonica, 15g of cynanchum paniculatum, 15g of stemona japonica, 10g of salvia miltiorrhiza, and 5g of licorice. The herbs are decocted in water, concentrated, and prepared into an oral liquid.

[0032] The following clinical pharmacodynamic trials demonstrate the beneficial effects of this invention.

[0033] Experimental Example 1: Clinical Trial of the Traditional Chinese Medicine Composition of the Invention

[0034] 1. Materials and Methods:

[0035] 1.1 General Information

[0036] One hundred and five patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) who met the inclusion criteria and were treated at the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine between May 2023 and February 2026 were selected and randomly divided into three groups using a random number table. The control group consisted of 35 patients, including 18 males and 17 females, aged 40–75 years (mean 59.07 ± 6.15 years), with a disease duration of 3–14 years (mean 6.56 ± 1.05 years). According to the GOLD classification, there were 6 patients in grade I (mild), 11 patients in grade II (moderate), 13 patients in grade III (severe), and 5 patients in grade IV (very severe). The traditional Chinese medicine control group consisted of 35 patients, including 16 males and 19 females; aged 45–77 years, with a mean age of (58.88 ± 6.54) years; disease duration 4–14 years, with a mean duration of (6.41 ± 1.34) years; and classified as Grade I (mild), 12 (moderate), 14 (severe), and 4 (extremely severe) according to the GOLD grading system. The observation group consisted of 35 patients, including 20 males and 15 females; aged 43–78 years, with a mean age of (60.12 ± 6.28) years; disease duration 2–15 years, with a mean duration of (6.32 ± 1.27) years; and classified as Grade I (mild), 13 (moderate), 11 (severe), and 6 (extremely severe) according to the GOLD grading system. There were no statistically significant differences in general characteristics among the three groups (P > 0.05), indicating comparability.

[0037] 1.2 Diagnostic criteria

[0038] According to the "Guidelines for the Diagnosis and Treatment of Chronic Obstructive Pulmonary Disease (2021 Revised Edition)", the diagnosis of Western medicine is as follows: clinical manifestations include cough, chest tightness, wheezing and shortness of breath; physical signs include: increased anteroposterior diameter of the chest, hyperresonance on chest percussion, dry and wet rales on auscultation, prolonged breathing in both lungs, and decreased breath sounds; history of exposure to risk factors; history of recurrent lower respiratory tract infections; forced expiratory volume in one second (FEV1) to forced vital capacity (FVC) ratio below 0.7 after using bronchodilators; and exclusion of other diseases that can cause similar symptoms.

[0039] Acute exacerbation: The patient's respiratory symptoms worsen acutely, requiring additional treatment. Coughing, wheezing, and shortness of breath worsen in a short period of time, purulent sputum increases, and fever may occur.

[0040] Traditional Chinese medicine diagnosis refers to the "International Guidelines for Clinical Practice of Traditional Chinese Medicine - Chronic Obstructive Pulmonary Disease", and the syndrome differentiation is phlegm-heat stasis in the lungs syndrome (phlegm-heat stagnation in the lungs syndrome combined with blood stasis syndrome): cough, chest tightness, wheezing, copious yellow or white phlegm that is thick and difficult to cough up, fever, thirst with a preference for cold drinks, dry stools, red tongue or with ecchymosis (spots) or tortuous and disordered sublingual veins, or with purplish-dark lips, nails and face, yellow or yellow-greasy tongue coating, and rapid or slippery pulse.

[0041] 1.3 Inclusion and Exclusion Criteria

[0042] Inclusion criteria: meeting the above diagnosis; in the acute exacerbation phase; aged 40–78 years; GOLD pulmonary function classification I–IV; signed informed consent form; good compliance.

[0043] Exclusion criteria: patients with interstitial lung disease, tuberculosis or other lung diseases; patients requiring invasive mechanical ventilation; pregnant or lactating patients; patients with other acute illnesses; patients with malignant tumors, hematopoietic abnormalities, immunodeficiency, or circulatory system diseases; patients with severe liver or kidney dysfunction; patients allergic to any component of the investigational drug; patients with mental illness or cognitive impairment; and patients with respiratory failure.

[0044] 1.4 Methods

[0045] The control group received Western medicine symptomatic treatment, including routine treatments such as oxygen inhalation, bronchodilator, expectorant, anti-inflammatory, anti-infective and acid-base balance maintenance, for 14 consecutive days.

[0046] The traditional Chinese medicine control group received routine Western medicine treatment (including oxygen therapy, bronchodilators, expectorants, anti-inflammatory drugs, anti-infection drugs, and maintenance of acid-base balance) combined with Qingqi Huatan Wan (Henan Jinhongtang Pharmaceutical Co., Ltd., National Medicine Approval Number: Z41021649, composed of Scutellaria baicalensis (processed), Trichosanthes kirilowii seed powder, Pinellia ternata (processed), Arisaema cum Bile, Citrus reticulata peel, Prunus armeniaca seed, Citrus aurantium, and Poria cocos, 6g each time, twice daily). Treatment continued for 14 days.

[0047] The research group received routine treatment (including oxygen therapy, bronchodilators, expectorants, anti-inflammatory drugs, anti-infection drugs, and maintenance of acid-base balance) combined with a decoction of *Ailanthus trifoliata* (composition: 15g of *Ailanthus trifoliata*, 15g of *Lepidium apetalum*, 10g of *Prunus armeniaca*, 10g of *Platycodon grandiflorus*, 10g of *Belamcanda chinensis*, 10g of *Citrus aurantium*, 15g of *Pinellia ternata*, 15g of *Fritillaria thunbergii*, 15g of *Inula japonica*, 15g of *Cynanchum paniculatum*, 15g of *Stemona japonica*, 10g of *Salvia miltiorrhiza*, and 5g of *Glycyrrhiza uralensis*. Each dose was decocted to 300ml and taken warm in three divided doses in the morning, noon, and evening) for 14 consecutive days.

[0048] 1.5 Observation Indicators

[0049] ① Detect the patient's arterial oxygen saturation (SaO2), carbon dioxide partial pressure (PaCO2), and blood oxygen partial pressure (PaO2) before and after treatment.

[0050] ② Complete blood count was performed before and after treatment, and the neutrophil / lymphocyte ratio (NLR) was calculated; serum procalcitonin (PCT) and C-reactive protein (CRP) levels were detected by enzyme-linked immunosorbent assay (ELISA).

[0051] ③ Before and after treatment, patients were evaluated using the mMRC (modified respiratory dyspnea scale) and the St. George's Respiratory Questionnaire (SGRQ).

[0052] 1.6 Criteria for Evaluating Therapeutic Effect

[0053] Clinical control: The patient's clinical symptoms have basically disappeared, and arterial blood gas indicators and inflammatory indicators tend to normalize; Improvement: The patient's clinical symptoms have improved, and arterial blood gas indicators and inflammatory indicators have improved; Ineffective: The above criteria are not met. Total effective rate = (Number of cases with clinical control + number of cases with improvement) / Total number of cases × 100%.

[0054] 1.7 Statistical Methods

[0055] Data were analyzed using SPSS 23.0 software. Quantitative data were presented in the form of (…). Data are expressed as mean ± standard deviation (s) and analyzed using the t-test; count data are expressed as percentages (%) and analyzed using the χ² test. ２ Test. P < 0.05 is considered statistically significant.

[0056] 2. Results

[0057] 2.1 Comparison of PCT, CRP, and NLR levels among different patient groups

[0058] After treatment, the levels of PCT, CRP, and NLR in the three groups decreased compared with those before treatment (P<0.05), and the decrease was more significant in the study group (P<0.05), as shown in Table 1.

[0059] Table 1. Comparison of PCT, CRP, and NLR levels among different groups (n=100,000) ±s)

[0060]

[0061] Note: *P<0.05 compared with pre-treatment levels; *P<0.05 compared with the control group. # p<0.05; compared with the traditional Chinese medicine control group, & p<0.05.

[0062] 2.2 Comparison of arterial blood gas parameters among different groups of patients

[0063] After treatment, PaCO2 and SaO2 in all three groups increased compared to before treatment, while PaO2 decreased compared to before treatment (P<0.05), and the improvement was more significant in the study group (P<0.05), as shown in Table 2.

[0064] Table 2 Comparison of arterial blood gas parameters among different groups of patients (n=1, 2000, 1 ... ±s)

[0065]

[0066] Note: 1 mm Hg ≈ 0.133 kPa; compared with before treatment, * P<0.05; compared with the control group, # p<0.05; compared with the traditional Chinese medicine control group, & p<0.05.

[0067] 2.3 Comparison of mMRC and SGRQ scores among different groups of patients

[0068] After treatment, the mMRC and SGRQ scores of the three groups decreased compared with those before treatment (P<0.05), and the decrease was more significant in the study group (P<0.05), as shown in Table 3.

[0069] Table 3 Comparison of mMRC and SGRQ scores among different groups (points, ±s)

[0070]

[0071] Note: Compared with before treatment, * P<0.05; compared with the control group, # p<0.05; compared with the traditional Chinese medicine control group, & p<0.05.

[0072] 2.4 Comparison of clinical efficacy among different groups of patients

[0073] After treatment, the total effective rate in the study group was higher than that in the control group (P<0.05), as shown in Table 4.

[0074] Table 4 Comparison of clinical efficacy among different groups of patients (cases, %)

[0075]

[0076] Note: Compared with the control group, * P<0.05; compared with the traditional Chinese medicine control group, # p<0.05;

[0077] 3. Conclusion

[0078] The Ai Ting compound can significantly improve the PCT, CRP, and NLR levels in patients with phlegm-heat stasis syndrome during acute exacerbation of COPD, as well as improve arterial blood gas indicators, mMRC, and SGRQ scores. It is more effective than Western medicine treatment alone or Western medicine combined with Qingqi Huatan pills.

[0079] Experimental Example 2: Animal Experiments of the Traditional Chinese Medicine Composition of the Present Invention

[0080] 1. Materials and Methods

[0081] 1.1 Fifty SPF-grade male Wistar rats, 6-7 weeks old, weighing between 190 and 225 g, with an average weight of (190.34 ± 9.25) g, were selected for the experiment. After one week of routine feeding, the experiment began. The rats were housed in separate cages, with 10 rats per cage. The room temperature was maintained between 22°C and 26°C, and the relative humidity between 55% and 65%. A 12-hour light cycle was maintained, and the rats were gavaged, fed, and had their water changed by designated personnel.

[0082] 1.2 Experimental drugs, reagents and instruments

[0083] The observation group received the following medication: Dwarf Lepidium Compound (15g of Dwarf Lepidium seed, 15g of Lepidium apetalum, 10g of Prunus armeniaca root, 10g of Platycodon grandiflorus, 10g of Belamcanda chinensis, 10g of Citrus aurantium, 15g of Pinellia ternata, 15g of Fritillaria thunbergii, 15g of Inula japonica, 15g of Cynanchum paniculatum, 15g of Stemona japonica, 10g of Salvia miltiorrhiza, and 5g of Glycyrrhiza uralensis), purchased from the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine. The daily dosage per kilogram of herbs for humans was 160g ÷ 60kg = 2.667 g / kg / day. The daily dosage for rats was 2.667 g / kg / day × 6.25 = 16.67 g / kg / day. The daily required amount of medicinal materials per rat is: 16.67 g / kg × rat body weight (kg). The gavage volume is set at 10 ml / kg. The required concentration = 16.67 g / kg ÷ 10 ml / kg = 1.667 g medicinal materials / ml. Based on a concentration of 1.667 g / ml, the required concentrated herbal solution is approximately 160 g ÷ 1.667 g / ml ≈ 96 ml. Taking a 200g rat as an example: Daily dosage: 16.67 g / kg / day × 0.2 kg = 3.334 g medicinal materials / day; Solution concentration: 1.6 g medicinal materials / ml; Gavage volume: 3.334 g ÷ 1.6 g / ml = 2.08 ml / day, administered once daily, 2 ml per gavage.

[0084] The control group received the following traditional Chinese medicine (patent CN 101843840 A: composed of 9g of Lepidium apetalum, 15g of Pheretima aspergillum, 12g of Fritillaria thunbergii, 9g of processed rhubarb, 9g of processed ephedra, 15g of Paeonia lactiflora, 25g of Lysimachia christinae, 9g of ginseng, 12g of Ophiopogon japonicus, and 9g of Acorus tatarinowii). The daily dosage per kilogram of medicinal material for a 60kg person was 124g ÷ 60kg = 2.067 g / kg / day. The daily dosage for rats was 2.067 g / kg / day × 6.25 = 12.92 g / kg / day. The 124g of medicinal material was decocted and concentrated to 100ml, yielding a solution with a concentration of 1.24 g of medicinal material / ml. The daily required amount of medicinal materials per rat is 12.92 g / kg × rat body weight (kg). Calculated based on a rat body weight of 200g, the daily required amount of medicinal materials per rat is: 12.92 g / kg × 0.2 kg = 2.584 g. Assuming an oral gavage volume of 10ml / kg, the oral gavage volume = 2.584 g ÷ 1.24 g / ml ≈ 2.08 ml / rat. This is distributed as one dose per day, 2ml per oral gavage.

[0085] The control group received acetylcysteine ​​tablets (Hainan Zanbang Pharmaceutical Co., Ltd.), 0.6g per tablet, 2 tablets (1.2g) per day. For a 60kg person, the daily dose is 1.2g / 60kg = 20 mg / kg / day. The daily dose for rats is 20 mg / kg / day × 6.25 = 125 mg / kg / day. Assuming a rat weight of 200g, the daily drug requirement per rat is 125 mg / kg × 0.2g = 25 mg / rat. Based on 2ml of oral gavage per rat per day, this requires a 12.5mg / ml solution.

[0086] Reagents: RIPA cell lysis buffer, lipopolysaccharide (LPS), tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), interleukin-6 (IL-6) and interleukin-8 (IL-8) kits.

[0087] 1.3 Research Methods

[0088] 1.3.1 Grouping: The animals were divided into five groups using a random number table method: normal group, model group, traditional Chinese medicine control group, Western medicine control group, and observation group (dwarf lepidium compound), with 10 animals in each group.

[0089] 1.3.2 Model Preparation: SPF-grade male Wistar rats, weighing (120.34±9.25 kg), were randomly divided into a blank control group, a smoke-induced lipopolysaccharide (LPS) model group, and an observation group, with 10 rats in each group. The model group rats were given passive smoking stimulation. They were placed in a self-made, sealed acrylic glass exposure chamber (50cm x 50cm x 50cm, with a 1cm x 1cm hole at the top and bottom), and eight cigarettes were lit simultaneously until they were completely burned and the smoke had mostly dissipated, for a total of 30 min / day. On days 1, 8, 15, and 22, 200 μL of LPS was injected into the trachea of ​​the rats (anesthetized by intraperitoneal injection of 10% chloral hydrate) (no smoke was given on the day of LPS injection). Starting from week 5, smoke was administered every other day for 30 min / day until week 6. The blank control group was not exposed to smoke, but an equal volume of physiological saline was instilled into the trachea using the same method.

[0090] 1.3.3 Drug administration: Rats in the observation group were given 2 ml of Dwarf Lepidium compound by gavage once a day for 4 consecutive weeks after the model was established on day 15. Rats in the normal group and the model group were given the same dose of physiological saline by gavage once a day for 4 consecutive weeks. Rats in the traditional Chinese medicine control group were given the patented traditional Chinese medicine by gavage once a day for 4 consecutive weeks after the model was established on day 15. Rats in the Western medicine control group were given 2 ml of acetylcysteine ​​tablets by gavage once a day for 4 consecutive weeks after the model was established on day 15.

[0091] 1.4 Observation Indicators

[0092] (1) After the last administration, the rats were anesthetized and their trachea was exposed. Tracheal intubation was performed, and the rats' forced vital capacity (FVC), peak expiratory flow (PEF), and forced expiratory volume in 0.1 s (FEV0.1) were measured using an animal ventilator.

[0093] (2) Under anesthesia, the rat's chest cavity was quickly opened, and the gavage needle was inserted into the trachea at the incision site. The right lung was repeatedly flushed with physiological saline three times, and the bronchoalveolar lavage fluid (BALF) was collected. The levels of tumor TNF-α, IL-17, IL-6 and IL-8 in the BALF were detected by ELISA.

[0094] (3) Rats were euthanized by cervical dislocation, and lung tissue was collected. The lung tissue was fixed in 4% formaldehyde for 24 hours, dehydrated in a gradient manner, embedded, and sectioned. After routine HE staining, the pathological changes in the rat lung tissue were examined.

[0095] 1.5 Statistical Analysis SPSS 19.0 statistical software was used for data analysis. Quantitative data conforming to a normal distribution were expressed as (x±s). t-tests were performed, and P<0.05 was considered statistically significant.

[0096] 2 Results

[0097] 2.1 Changes in lung function-related indicators in each group of rats

[0098] Compared with the normal group, the PFE, FEV0.1 and FVC of rats in the model group were significantly decreased (P<0.05); compared with the model group, the PFE, FEV0.1 and FVC of the traditional Chinese medicine control group, the western medicine control group and the observation group (Ai Ting compound) were significantly improved (P<0.05); compared with the traditional Chinese medicine control group and the western medicine control group, the improvement of PFE, FEV0.1 and FVC in the observation group (Ai Ting compound) was more significant (P<0.05), as shown in Table 5.

[0099] Table 5 Comparison of changes in lung function-related indicators among different groups of rats ( ±s)

[0100]

[0101] Note: Compared with the normal group. * P<0.05; compared with the model group, # P<0.05, compared with the traditional Chinese medicine control group, & P<0.05, compared with the Western medicine control group, % P<0.05.

[0102] 2.2 Pathological changes in rat lung tissue

[0103] In the normal group, the alveolar structure and bronchial walls of rats were intact, with no ciliary loss and no thickening of the bronchial walls. In the model group, the alveolar structure was damaged, fused into bullae, the alveolar septa were significantly thickened, the bronchial walls were thickened and the lumen was narrowed, cilia were lost and collapsed, epithelial cells were shed, and there was significant inflammatory cell infiltration. In the traditional Chinese medicine control group and the western medicine control group, the alveolar structure was damaged, with some fusion into bullae, local thickening of the bronchial walls, and inflammatory cell infiltration. These manifestations were significantly reduced compared to the model group. In the observation group, there was a small amount of inflammatory cell infiltration around the blood vessels and bronchial walls, the bronchial walls were slightly thickened, the local lumen was deformed, some cilia were collapsed, and a small number of alveoli were fused. These manifestations were significantly reduced compared to the traditional Chinese medicine and western medicine control groups. Figure 1 .

[0104] 2.3 Levels of TNF-α, IL-17, IL-6 and IL-8 in BALF of rats in each group

[0105] The levels of TNF-α, IL-17, IL-6, and IL-8 in the model group rats were all higher than those in the normal group (P < 0.05). The expression of TNF-α, IL-17, IL-6, and IL-8 in the traditional Chinese medicine control group, the western medicine control group, and the observation group (Ai Ting compound) were all significantly lower than those in the model group, and the differences were statistically significant (P < 0.05). The expression of TNF-α, IL-17, IL-6, and IL-8 in the observation group (Ai Ting compound) was significantly lower than that in the traditional Chinese medicine control group and the western medicine control group (P < 0.05), as detailed in Table 6.

[0106] Table 6. Comparison of TNF-α, IL-17 and IL-8 levels in BALF of rats in different groups ( ±s)

[0107]

[0108] Note: Compared with the normal group. * P<0.05; compared with the model group, # P<0.05, compared with the traditional Chinese medicine control group, & P<0.05, compared with the Western medicine control group, % P<0.05.

[0109] 3. Conclusion

[0110] Compared with the control drugs, the traditional Chinese medicine composition of the present invention (Dwarf Lepidium compound) can significantly improve lung function in a rat model of COPD, improve inflammatory cell infiltration in lung tissue, cilia and alveolar destruction and airway abnormalities, and reduce the levels of TNF-α, IL-17, IL-6 and IL-8 inflammatory factors in bronchoalveolar lavage fluid.

Claims

1. A traditional Chinese medicine composition for treating or / and adjunctive treating chronic obstructive pulmonary disease, characterized in that: It is prepared from the following raw materials in the indicated weight ratios: 12-18 parts of Dwarf Tea, 12-18 parts of Lepidium Seed, 8-12 parts of Apricot Kernel, 8-12 parts of Platycodon Root, 8-12 parts of Belamcanda Rhizome, 8-12 parts of Bitter Orange Peel, 12-18 parts of Prepared Pinellia Rhizome, 12-18 parts of Fritillaria Bulb, 12-18 parts of Inula Flower, 12-18 parts of Cynanchum Root, 12-18 parts of Stemona Root, 8-12 parts of Salvia miltiorrhiza, and 4-6 parts of Licorice Root.

2. The traditional Chinese medicine composition for treating or / and adjuvant treatment of chronic obstructive pulmonary disease according to claim 1, characterized in that: It is prepared from the following raw materials in the indicated weight ratios: 15 parts of dwarf tea, 15 parts of lepidium seed, 10 parts of apricot kernel, 10 parts of platycodon root, 10 parts of belamcanda rhizome, 10 parts of immature bitter orange peel, 15 parts of prepared pinellia tuber, 15 parts of fritillaria thunbergii, 15 parts of inula flower, 15 parts of cynanchum paniculatum, 15 parts of stemona root, 10 parts of salvia miltiorrhiza, and 5 parts of licorice root.

3. The traditional Chinese medicine composition for treating and / or adjuvant treatment of chronic obstructive pulmonary disease according to claim 1 or 2, characterized in that: It is prepared into a commonly used oral formulation by adding pharmaceutically acceptable excipients or auxiliary ingredients, using the original drug powder, water or organic solvent extract as the active ingredient.

4. The traditional Chinese medicine composition for treating or / and adjuvant treatment of chronic obstructive pulmonary disease according to claim 3, characterized in that: The oral preparations mentioned are oral liquids, tablets, capsules, pills, granules, and oral liquids.

5. A method for preparing a traditional Chinese medicine composition for treating or / and adjuvant treating chronic obstructive pulmonary disease according to any one of claims 1-4, characterized in that: It includes the following steps: a. Weigh the raw materials according to the specified weight ratio; b. The active pharmaceutical ingredient is powdered, extracted with water or organic solvent, and then pharmaceutically acceptable excipients or auxiliary ingredients are added to prepare a commonly used oral pharmaceutical preparation.

6. Use of the traditional Chinese medicine composition according to any one of claims 1-4 in the preparation of a medicament for treating chronic obstructive pulmonary disease.

7. The use according to claim 6, characterized in that: The medication described is for the treatment of acute exacerbations of chronic obstructive pulmonary disease.

8. The use according to claim 6 or 7, characterized in that: The aforementioned medication is for treating chronic obstructive pulmonary disease (COPD) characterized by phlegm-heat accumulation in the lungs and blood stasis.

9. The use according to claim 8, characterized in that: The aforementioned drug has the functions of ventilating the lungs and relieving nausea, clearing heat and resolving phlegm, and promoting blood circulation and unblocking collaterals.

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