Use of traditional Chinese medicine composition in preparation of medicine for preventing and treating chronic obstructive pulmonary disease

Abstract

This invention relates to the field of traditional Chinese medicine (TCM) technology, and particularly to the application of TCM compositions in the preparation of drugs for the prevention and treatment of chronic obstructive pulmonary disease (COPD). The TCM composition described in this invention is prepared from Magnolia biondii, Perilla frutescens, Schizonepeta tenuifolia, Angelica dahurica, Arctium lappa, Xanthium sibiricum, Schisandra chinensis, Pseudostellaria heterophylla, and Glycyrrhiza uralensis. This invention has found that this composition can significantly improve the forced expiratory volume in 3 seconds (FEV1), forced vital capacity, and peak expiratory flow rate in rats; significantly regulate the level of the inflammatory factor IL-8 in rat serum; increase the levels of CD3+ and CD4+ in mouse serum; significantly decrease the level of CD8+; and significantly improve the level of the inflammatory factor IL-1β in serum. It also shows good therapeutic effects on COPD models induced by smoke inhalation combined with LPS in mice and rats.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, and in particular to the application of traditional Chinese medicine compositions in the preparation of drugs for the prevention and treatment of chronic obstructive pulmonary disease. Background Technology

[0002] Chronic obstructive pulmonary disease (COPD) is a common chronic disease characterized by airflow obstruction, involving chronic bronchitis and / or emphysema, and associated with an abnormal inflammatory response to harmful gases and particles. It can further develop into pulmonary heart disease and respiratory failure.

[0003] The exact cause of chronic obstructive pulmonary disease (COPD) is unclear. It is generally believed that factors associated with chronic bronchitis and obstructive emphysema may contribute to its pathogenesis. Identified risk factors can be broadly categorized into external and internal factors. External factors include smoking, inhalation of dust and chemicals, air pollution, respiratory infections, and lower socioeconomic status. Internal factors include genetic factors, increased airway reactivity, and various causes of poor lung development or growth during pregnancy, the neonatal period, infancy, or childhood. The disease has a slow onset and a long course. Early stages may be asymptomatic; as the disease progresses, clinical manifestations mainly include chronic cough, sputum production, shortness of breath, dyspnea, wheezing, and chest tightness.

[0004] Currently, the main types of drugs used to treat chronic obstructive pulmonary disease (COPD) include the following:

[0005] Bronchodilators: These medications relax bronchial smooth muscle, relieve airflow limitation, and thus improve patient symptoms. Commonly used bronchodilators include β2 receptor agonists (such as salbutamol and terbutaline), M receptor antagonists (such as ipratropium bromide and tiotropium bromide), and theophylline (such as aminophylline).

[0006] Glucocorticoids: Glucocorticoids can reduce airway inflammation and improve airflow limitation, playing an important role in the stable phase treatment of COPD patients. Commonly used glucocorticoids include inhaled glucocorticoids (such as budesonide and fluticasone) and oral glucocorticoids (such as prednisone and methylprednisolone).

[0007] Phosphodiesterase inhibitors: These drugs inhibit the activity of phosphodiesterase, thereby reducing the degradation of intracellular cyclic adenosine monophosphate (cAMP) and increasing the concentration of cAMP in cells. This relaxes bronchial smooth muscle and relieves airflow limitation. Commonly used phosphodiesterase inhibitors include theophylline (such as aminophylline).

[0008] Antibiotics: COPD patients often have concurrent bacterial infections, therefore antibiotics are needed for anti-infective treatment. Commonly used antibiotics include penicillins, cephalosporins, macrolides, and quinolones.

[0009] It is evident that current treatments for COPD primarily involve hormones and antibiotics, but the side effects of these drugs remain a significant concern. In recent years, with the advancement of medical research, COPD treatment plans have been continuously evolving. The field of traditional Chinese medicine should actively participate in the prevention and treatment of chronic obstructive pulmonary disease, developing and researching appropriate prescriptions. Summary of the Invention

[0010] In view of this, the technical problem to be solved by the present invention is to provide the application of traditional Chinese medicine composition in the preparation of drugs for the prevention and treatment of chronic obstructive pulmonary disease.

[0011] This invention provides the application of a traditional Chinese medicine composition in the preparation of a drug for the prevention and treatment of chronic obstructive pulmonary disease.

[0012] In this invention, the traditional Chinese medicine composition comprises the following raw materials in parts by weight: 1-6 parts Magnolia biondii, 1-6 parts Perilla frutescens, 1-5 parts Schizonepeta tenuifolia, 1-5 parts Angelica dahurica, 1-5 parts Arctium lappa, 1-5 parts Xanthium sibiricum, 1-5 parts Schisandra chinensis, 1-6 parts Codonopsis pilosula, and 1-3 parts Glycyrrhiza uralensis.

[0013] In this invention, the prevention and treatment include: reducing cytokine levels and / or improving lung function.

[0014] In this embodiment of the invention, the cytokines are cytokines from serum.

[0015] Cytokines participate in the airway inflammatory response, fibrosis, and immune dysregulation processes of COPD, playing a crucial role in the pathogenesis and progression of COPD. Among them, IL-8, as an important inflammatory cytokine, participates in the chronic airway inflammatory process of COPD; while CD3, CD4, and CD8, as marker molecules of T lymphocytes, are present in increased numbers in the lung tissue and blood of COPD patients, releasing large amounts of inflammatory factors and further exacerbating the airway inflammatory response. Therefore, research and treatment targeting these molecules may provide new ideas and methods for the treatment of COPD. In this invention, the traditional Chinese medicine composition can inhibit cytokines including IL-8, CD3, CD4, or CD8. Experiments of this invention show that the traditional Chinese medicine composition described in this invention can significantly reduce the levels of IL-8, CD3, CD4, or CD8 in serum. CD8 is CD8a.

[0016] Pulmonary function testing is one of the important means of diagnosing COPD. Through pulmonary function testing, a patient's lung ventilation and gas exchange function can be assessed, thereby determining whether airflow limitation and the possibility of COPD exist. Simultaneously, pulmonary function testing can also be used to monitor the progression of COPD and the treatment effect, providing important reference for clinical diagnosis and treatment. Pulmonary function tests include FVC (forced vital capacity), FEV0.3 (forced expiratory volume in 0.3 seconds), FEV0.3 / FVC (the ratio of forced expiratory volume in 0.3 seconds to forced vital capacity), and PEF (peak expiratory flow rate), all of which are important indicators in pulmonary function testing. Experiments in this invention show that the traditional Chinese medicine composition described in this invention can significantly improve FVC, FEV0.3, FEV0.3 / FVC, or PEF.

[0017] In this invention, the traditional Chinese medicine composition can treat chronic obstructive pulmonary disease (COPD) caused by harmful gases. In some embodiments, the harmful gases are cigarette smoke.

[0018] In this invention, the effective dose of the traditional Chinese medicine composition is 46g of raw herbs per day.

[0019] In this invention, the preparation method of the traditional Chinese medicine composition includes:

[0020] The magnolia flower, perilla leaf, schizonepeta, and cocklebur fruit were mixed, soaked in water, distilled, and the volatile oil was extracted. Then, the volatile oil inclusion complex was prepared for later use. The remaining residue was boiled again, filtered, and the resulting decoction was combined and concentrated to obtain thick paste I.

[0021] The Codonopsis pilosula and Glycyrrhiza uralensis were mixed, decocted with water, filtered, and the resulting decoction was concentrated to obtain a thick paste II.

[0022] The Angelica dahurica, Arctium lappa, and Schisandra chinensis were mixed and extracted by reflux with ethanol. The obtained ethanol extract was concentrated to obtain a thick paste III.

[0023] After combining the three thick pastes I, II, and III, they were dried under reduced pressure and pulverized, and then the volatile oil inclusion complex was added and mixed evenly.

[0024] Furthermore, the present invention also provides a medicament for the prevention and treatment of chronic obstructive pulmonary disease, comprising pharmaceutically acceptable excipients and the following raw materials in parts by weight: 1-6 parts Magnolia biondii, 1-6 parts Perilla frutescens, 1-5 parts Schizonepeta tenuifolia, 1-5 parts Angelica dahurica, 1-5 parts Arctium lappa, 1-5 parts Xanthium sibiricum, 1-5 parts Schisandra chinensis, 1-6 parts Codonopsis pilosula, and 1-3 parts Glycyrrhiza uralensis.

[0025] The dosage forms of the drugs described in this invention include, but are not limited to, decoctions, granules, capsules, tablets, oral liquids, pills, tinctures, syrups, suppositories, gels, sprays, and / or injections.

[0026] In some embodiments provided by the present invention, the capsule is a hard capsule or a soft capsule.

[0027] In some embodiments provided by the present invention, the tablet is an oral tablet or a dental tablet.

[0028] Oral tablets refer to tablets intended for oral administration. Most of these tablets contain drugs that are absorbed through the gastrointestinal tract to exert their effects, while some contain drugs that exert their effects locally within the gastrointestinal tract. In some embodiments provided by this invention, the oral tablets are ordinary compressed tablets, dispersible tablets, effervescent tablets, chewable tablets, coated tablets, or sustained-release tablets.

[0029] The pharmaceutically acceptable excipients include one or more of the following: fruit powder, flavoring, sweetener, acidulant, filler, lubricant, preservative, suspending agent, food coloring, diluent, emulsifier, disintegrant, or plasticizer.

[0030] The medicament described in this invention also includes other treatment agents for chronic obstructive pulmonary disease (COPD), including at least one of aminophylline, prednisone, methylprednisolone, budesonide, fluticasone, antibiotics, terbutaline, salbutamol, levosalbutamol, salmeterol, formoterol, or ipratropium bromide.

[0031] The traditional Chinese medicine composition described in this invention is prepared from Magnolia biondii, Perilla frutescens, Schizonepeta tenuifolia, Angelica dahurica, Arctium lappa, Xanthium sibiricum, Schisandra chinensis, Pseudostellaria heterophylla, and Glycyrrhiza uralensis. This invention has found that this composition can significantly improve the forced expiratory volume in 3 seconds, forced vital capacity, and peak expiratory flow rate in rats; significantly regulate the level of the inflammatory factor IL-8 in rat serum; increase the levels of CD3+ and CD4+ in mouse serum; significantly decrease the level of CD8+; and significantly improve the level of the inflammatory factor IL-1β in serum. It also shows good therapeutic effects on smoke-induced and LPS-induced chronic obstructive pulmonary disease models in mice and rats. Detailed Implementation

[0032] This invention provides the application of traditional Chinese medicine compositions in the preparation of drugs for the prevention and treatment of chronic obstructive pulmonary disease. Those skilled in the art can refer to the content of this document and appropriately modify the process parameters to achieve the desired results. It should be particularly noted that all similar substitutions and modifications are obvious to those skilled in the art and are considered to be included in this invention. The methods and applications of this invention have been described through preferred embodiments. Those skilled in the art can obviously make modifications or appropriate alterations and combinations to the methods and applications described herein without departing from the content, spirit, and scope of this invention to realize and apply the technology of this invention.

[0033] This invention provides the application of a traditional Chinese medicine composition in the preparation of drugs for the treatment or prevention of chronic obstructive pulmonary disease. The composition comprises: 1-6 parts Magnolia biondii, 1-6 parts Perilla frutescens, 1-5 parts Schizonepeta tenuifolia, 1-5 parts Angelica dahurica, 1-5 parts Arctium lappa, 1-5 parts Xanthium sibiricum, 1-5 parts Schisandra chinensis, 1-6 parts Pseudostellaria heterophylla, and 1-3 parts Glycyrrhiza uralensis. The composition of this invention can be directly ground into powder, or it can be an extract obtained through conventional methods in the art. The traditional Chinese medicine raw materials used in the composition of this invention can also be used by directly grinding into powder, extracting, or in other processed forms.

[0034] Further, the composition comprises: 2-5 parts by weight of Magnolia biondii, 2-5 parts by weight of Perilla frutescens, 2-4 parts by weight of Schizonepeta tenuifolia, 2-4 parts by weight of Angelica dahurica, 2-4 parts by weight of Arctium lappa, 2-4 parts by weight of Xanthium sibiricum, 2-4 parts by weight of Schisandra chinensis, 2-5 parts by weight of Pseudostellaria heterophylla, and 1-2.5 parts by weight of raw Glycyrrhiza uralensis.

[0035] Further, the composition comprises: 3 parts by weight of Magnolia biondii, 3 parts by weight of Perilla frutescens, 2.5 parts by weight of Schizonepeta tenuifolia, 2.5 parts by weight of Angelica dahurica, 2.5 parts by weight of Arctium lappa, 2.5 parts by weight of Xanthium sibiricum, 2.5 parts by weight of Schisandra chinensis, 3 parts by weight of Pseudostellaria heterophylla, and 1.5 parts by weight of Glycyrrhiza uralensis.

[0036] Specifically, the aforementioned chronic obstructive pulmonary disease medications include oral dosage forms, injectable dosage forms, or topical dosage forms.

[0037] The dosage form of the drug of the present invention is prepared by weighing the raw material in proportion, and then adding pharmaceutically acceptable excipients such as fillers, disintegrants, lubricants, suspending agents, binders, sweeteners, flavoring agents, preservatives, and matrices during the preparation process, and preparing it according to conventional production methods in the pharmaceutical field to produce a pharmaceutically acceptable conventional dosage form, including but not limited to decoctions, granules, capsules, tablets, oral liquids, pills, tinctures, syrups, suppositories, gels, sprays, and injections.

[0038] The present invention also provides a method for preparing a composition for chronic obstructive pulmonary disease, the method comprising:

[0039] (1) Take the selected weight proportions of Magnolia biondii, Perilla frutescens, Schizonepeta tenuifolia, Xanthium sibiricum and Angelica dahurica, mix them with water and soak them, distill them to extract the volatile oil, add conventional excipients to make volatile oil inclusion complex, and set aside; continue to decoct the remaining residue, filter and combine the decoctions to concentrate to obtain thick paste I.

[0040] (2) Take the selected weight proportions of Codonopsis pilosula and raw licorice root, add water and decoct, filter and concentrate the decoction to obtain thick paste II;

[0041] (3) Take the selected weight proportions of burdock fruit and schisandra fruit, mix them and crush them into coarse powder, add ethanol and reflux to extract, and concentrate the obtained ethanol extract to obtain thick paste III;

[0042] (4) After combining the above-prepared thick paste I, thick paste II and thick paste III, dry them under reduced pressure and pulverize them, add the volatile oil inclusion complex prepared in step (1) above and mix well, add conventional excipients and prepare a clinically acceptable dosage form according to conventional process.

[0043] Furthermore, the aforementioned method for preparing the composition may include the following steps:

[0044] (1) Take the selected weight proportions of Magnolia biondii, Perilla frutescens, Schizonepeta tenuifolia, Xanthium sibiricum and Angelica dahurica, add 10 times the weight of the drug in water, distill for 4 hours, extract the volatile oil, add conventional excipients to make a fine powder of volatile oil inclusion complex, and set aside. Continue to decoct the remaining residue for 1.5 hours, filter and combine the decoctions to concentrate to a thick paste I with a relative density of 1.05 to 1.08 (55℃±5℃);

[0045] Take the thick paste I and add 95% ethanol solution while stirring. Precipitate with 80% alcohol and let it stand for no less than 24 hours. Take the supernatant and concentrate it to a thick paste with a relative density of 1.20 to 1.26 (55℃±5℃).

[0046] (2) Take the selected weight proportions of Codonopsis pilosula and raw licorice root, add 10 times the weight of the medicine in water, decoct twice, 2.5 hours each time, filter, and concentrate the resulting decoction to a thick paste II with a relative density of 1.20 to 1.25 (55℃±5℃);

[0047] (3) Take the selected weight proportions of burdock seed and schisandra seed and mix them together. Add 6 times the weight of the drug and 70% ethanol. Reflux and extract 3 times, 2.5 hours each time. Concentrate the obtained ethanol extract to a thick paste III with a relative density of 1.03-1.05 (55℃±5℃)1.30.

[0048] (4) After passing the prepared thick pastes I, II, and III through a 200-mesh sieve, place them in a spray tank, stir, and keep warm at 45-55℃ for later use. Place the fine powder of volatile oil inclusion complex, appropriate amounts of steviol glycosides and dextrin prepared in step (1) into the hopper of a fluidized bed granulator, preheat the material to 50℃, and spray in the liquid medicine. During the granulation process, the material temperature should be ≤60℃. After the liquid medicine is sprayed out, continue to dry the granules until the moisture content is ≤4.0%, release them, and granulate them to obtain the final product.

[0049] The present invention also proposes a composition for treating or preventing chronic obstructive pulmonary disease, characterized in that the composition comprises: 1-6 parts of Magnolia biondii, 1-6 parts of Perilla frutescens, 1-5 parts of Schizonepeta tenuifolia, 1-5 parts of Angelica dahurica, 1-5 parts of Arctium lappa, 1-5 parts of Xanthium sibiricum, 1-5 parts of Schisandra chinensis, 1-6 parts of Pseudostellaria heterophylla, and 1-3 parts of Glycyrrhiza uralensis.

[0050] Furthermore, the composition comprises: 2-5 parts of Magnolia biondii, 2-5 parts of Perilla frutescens, 2-4 parts of Schizonepeta tenuifolia, 2-4 parts of Angelica dahurica, 2-4 parts of Arctium lappa, 2-4 parts of Xanthium sibiricum, 2-4 parts of Schisandra chinensis, 2-5 parts of Pseudostellaria heterophylla, and 1-2.5 parts of raw Glycyrrhiza uralensis.

[0051] Furthermore, the composition comprises: 3 parts Magnolia biondii, 3 parts Perilla frutescens, 2.5 parts Schizonepeta tenuifolia, 2.5 parts Angelica dahurica, 2.5 parts Arctium lappa, 2.5 parts Xanthium sibiricum, 2.5 parts Schisandra chinensis, 3 parts Codonopsis pilosula, and 1.5 parts Glycyrrhiza uralensis.

[0052] The drug described in this invention can significantly improve the forced expiratory volume, forced vital capacity, and peak expiratory flow rate in rats at 03 seconds, significantly regulate the content of the inflammatory factor IL-8 in rat serum, significantly improve the content of the inflammatory factor IL-1β in mouse serum, and significantly reduce the levels of CD3+ and CD4+ in mouse serum, suggesting that the traditional Chinese medicine composition can effectively reduce inflammatory response, enhance the innate immunity of animals, and improve lung function. It also has a good therapeutic effect on the chronic obstructive pulmonary disease model induced by smoke fumigation combined with LPS in mice and rats.

[0053] The test materials used in this invention are all common commercial products and can be purchased on the market.

[0054] Unless otherwise specified, all experiments in the following experiments were conducted under standard conditions or conditions recommended by the manufacturer. Active pharmaceutical ingredients (APIs) or excipients, as well as reagents or instruments whose manufacturers are not specified, are all commercially available products. Unless otherwise stated, all percentages, ratios, proportions, or parts are by weight.

[0055] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as are familiar to those skilled in the art. Furthermore, any methods and materials similar to or equivalent to those described herein may be applied to this invention.

[0056] The present invention will be further illustrated below with reference to the embodiments:

[0057] Example 1: Preparation of granules of the composition of the present invention

[0058] The composition of this invention is made from the following raw materials: 300g Magnolia biondii, 300g Perilla frutescens, 250g Schizonepeta tenuifolia, 250g Angelica dahurica, 250g Arctium lappa, 250g Xanthium sibiricum, 250g Schisandra chinensis, 300g Codonopsis pilosula, and 150g Glycyrrhiza uralensis.

[0059] The composition of the present invention is prepared according to the following method:

[0060] (1) Take Magnolia biondii, Perilla frutescens, Schizonepeta tenuifolia, Xanthium sibiricum and Angelica dahurica, add 10 times the weight of the drugs in water, distill for 4 hours, extract the volatile oil, add conventional excipients to make a fine powder of volatile oil inclusion complex, and set aside. Continue to decoct the remaining residue for 1.5 hours, filter and combine the decoctions to concentrate to a thick paste I with a relative density of 1.05~1.08 (55℃±5℃);

[0061] Take the thick paste I and add 95% ethanol solution while stirring. Precipitate with 80% alcohol and let it stand for no less than 24 hours. Take the supernatant and concentrate it to a thick paste with a relative density of 1.20 to 1.26 (55℃±5℃).

[0062] (2) Take the aforementioned Codonopsis pilosula and Glycyrrhiza uralensis, add 10 times the weight of the medicine in water, decoct twice, 2.5 hours each time, filter, and concentrate the resulting decoction to a thick paste II with a relative density of 1.20 to 1.25 (55℃±5℃);

[0063] (3) Take burdock seed and schisandra fruit, add 6 times the weight of the drug and 70% ethanol, reflux extract 3 times, 2.5 hours each time, and concentrate the obtained ethanol extract to a thick paste III with a relative density of 1.03~1.05 (55℃±5℃)1.30;

[0064] (4) After passing the prepared thick paste I, thick paste II and thick paste III through a 200-mesh sieve, place them in a spray tank, stir, keep warm at 45-55℃, and set aside to obtain the intermediate of the traditional Chinese medicine composition. Place the volatile oil inclusion complex fine powder, steviol glycoside and dextrin prepared in step (1) into the hopper of a fluidized bed granulator, preheat it to 50℃, spray in the medicine liquid, and keep the material temperature ≤60℃ during the granulation process. After the medicine liquid is sprayed out, continue to dry the granules until the moisture content is ≤4.0%, release them, granulate them, and obtain the final product.

[0065] Example 2: Effects of the Traditional Chinese Medicine Composition on COPD Caused by Smoke and LPS Combination

[0066] 1. Experimental Materials

[0067] 1.1 Animals

[0068] Ninety male SD rats, SPF grade, weighing 180–220g, were purchased from Nantong University. Housing conditions: room temperature 20–26℃, relative humidity controlled at 40%–70%, stocking density 5 rats / cage.

[0069] 1.2 Drugs

[0070] The traditional Chinese medicine composition, an intermediate prepared according to the method of Example 1, is from Jiangsu Kangyuan Pharmaceutical Co., Ltd.; the aminophylline tablets are a product of Tianjin Lisheng Pharmaceutical Co., Ltd., batch number: 2020009; specifications: 0.1g / tablet, 100 tablets / bottle.

[0071] 1.3 Reagents

[0072] LPS: SIGMA, extracted from E. coli O55: B5, batch number 039M4004V; 0.9% sodium chloride solution, Shijiazhuang No. 4 Pharmaceutical Co., Ltd., specification: 500mL / bottle, batch number: 2012192103; formaldehyde, Nanjing Chemical Reagent Co., Ltd., specification: 500mL / bottle, batch number: 200517018E; chloral hydrate, Shanghai Guoyao Group Chemical Reagent Co., Ltd., specification: 250g / bottle, batch number: 20201129; penicillin sodium for injection, Harbin Pharmaceutical Group Pharmaceutical Factory, batch number: P2101719; IL-8 ELISA kit (Solepro, batch number: 2301021)

[0073] 1.4 Instruments

[0074] Ultra-low temperature freezer (Haier, model: DW-86L728); electronic balance (Sartorius Scientific Instruments, model: BSA224S-CW); DHG-9076A electric thermostatic drying oven (Shanghai Jinghong Experimental Equipment Co., Ltd.); PowerLab8 / 35 biosignal acquisition system (AD Instruments, Australia); CENTRFUGE5840 refrigerated centrifuge (Eppendorf); MD FLEX-STION3 microplate reader.

[0075] 2. Dosage design

[0076] The daily dosage of the traditional Chinese medicine composition is 46.04g of crude drug / day. Based on the body surface area calculation method, the equivalent dose for rats is 46.04g / 60kg × 6.2 = 4.75g crude drug / kg ≈ 4.8g crude drug / kg. Following a 1 / 4:1 / 2:1 dosing regimen, the low dose is 1.2g crude drug / kg, and the medium dose is 2.4g crude drug. Administer by gavage at a dose of 0.2mL / 10g, once daily.

[0077] 3. Experimental Methods

[0078] SD rats were acclimatized for 5 days with free access to feed and water. They were then randomly divided into four groups according to their body weight: a normal control group, a model control group, a positive control group, and high, medium, and low dose groups of the traditional Chinese medicine combination, with 10 rats in each group.

[0079] On days 1 and 14 of each group, rats were injected intratracheally with 200 μg / 200 μL of LPS. From days 2 to 30 (except day 14), rats were exposed to 5% cigarette smoke (Nanjing brand) for 1 hour / day, twice a day, to replicate the COPD model. Rats that did not meet the model requirements were discarded. The criteria for successful model establishment were: ① curled-up position; ② reduced food intake and weight loss; ③ soft or loose stools; ④ dull coat; ⑤ lethargy; ⑥ cough, wheezing, and airway rales; ⑦ emphysema.

[0080] Normal control group: On days 1 and 14, normal saline was administered via intratracheal instillation without fumigation. Different dosage groups of the herbal composition granules of this invention (1.2g crude drug / kg, 2.4g crude drug / kg, 4.8g crude drug / kg) and the aminophylline tablet positive control group were administered by gavage at a dose of 10ml / kg once daily for 30 consecutive days. Thirty minutes after the last administration, anesthetized rats were anesthetized by intraperitoneal injection of 0.35g / kg of 10% chloral hydrate for testing and sample collection.

[0081] 4. Experimental Results

[0082] Rats were anesthetized with 0.35 g / kg of 10% chloral hydrate. The skin of the neck was longitudinally incised to expose the trachea. An inverted "T" shaped incision was made under the cricoid cartilage, and an endotracheal tube with a three-way valve was inserted. One end was connected to an animal ventilator, and the other end was connected to a signal acquisition system to measure respiratory parameters. Forced expiratory volume in 0.3 seconds (FEV0.3), forced vital capacity (FVC), FEV0.3 / FVC, and peak expiratory flow (PEF) were measured.

[0083] 4.1 Effects on respiratory parameters in rats

[0084] The results showed that FVC, FEV0.3, FEV0.3 / FVC, and PEF in the model group were significantly lower than those in the normal group (P<0.01, P<0.001, P<0.05, P<0.001), indicating successful model establishment. The high-dose group and the positive control group of the traditional Chinese medicine composition showed significant improvements in FVC, FEV0.3, and PEF compared to the model group (P<0.05, P<0.001, P<0.05). The medium-dose group of the traditional Chinese medicine composition showed a significant improvement in FEV0.3 compared to the model group (P<0.05). The results are shown in Table 1. This indicates that the composition can improve symptoms such as emphysema caused by COPD.

[0085] Table 1 Effects on pulmonary function in rats with chronic obstructive pulmonary disease

[0086]

[0087] Note: Compared with the control group, ▲P<0.05, ▲▲P<0.01, ▲▲▲P<0.001; compared with the model group, *P<0.05, **P<0.01, ***P<0.001.

[0088] 5.2 Effects on serum inflammatory factor levels in rats

[0089] Compared with the blank control group, the serum IL-8 level in the model group rats was significantly increased (P < 0.001). Compared with the model group, the serum IL-8 level in the positive control group, the high-dose group of the traditional Chinese medicine composition, the medium-dose group, and the low-dose group of rats was significantly decreased (P < 0.01). The results are shown in Table 2.

[0090] Table 2. Effects of serum inflammatory factor IL-8 levels in rats with chronic obstructive pulmonary disease.

[0091] Blank control group 10 25.29±2.33*** Model control group 10 49.21±7.46▲▲▲ Positive drug group 10 26.54±3.26*** low-dose group 10 36.73±5.36*** medium dose group 10 28.65±4.25*** High-dose group 10 24.48±3.05***

[0092] Note: Compared with the control group, ▲P<0.05, ▲▲P<0.01, ▲▲▲P<0.001; compared with the model group, *P<0.05, **P<0.01, ***P<0.001.

[0093] Example 3: Effect of the traditional Chinese medicine composition on the serum inflammatory factor levels in mice with chronic obstructive pulmonary disease

[0094] 1. Experimental Materials

[0095] 1.1 Animals

[0096] ICR mice, male, SPF grade, 80 mice, weighing 16-18g, were purchased from the Comparative Medicine Center of Yangzhou University. Housing environment: room temperature 20-26℃, relative humidity controlled at 40-70%, stocking density 5 mice / cage.

[0097] 1.2 Drugs

[0098] The traditional Chinese medicine composition, the intermediate prepared according to the method of Example 1, is from Jiangsu Kangyuan Pharmaceutical Co., Ltd.; salbutamol injection (Shanghai Hefeng Pharmaceutical Co., Ltd., approval number: National Drug Approval Number H31022208); physiological saline (Chenxin Pharmaceutical Co., Ltd., batch number: 2101282721); chloral hydrate (Sinopharm Chemical Reagent Co., Ltd., batch number: 20200320).

[0099] 1.3 Reagents

[0100] Lipopolysaccharide (LPS; batch number 12180309): Sigma-Aldrich, USA. IL-1β ELISA kit (Solepro, batch number: 2302045); NovoCyte-QC control microspheres, Agilent Technologies, batch number: 8000004, specification: 2ml / vial; eBioscienceTM Flow cytometry staining buffer, Invitrogen, lot number: 00-4222-26, specification: 600ml / vial; CD16 / CD32 Monoclonal Antibody (93), eBioscience TM Invitrogen, lot number: 14-0161-82, specification: 100ug / vial; CD3 Monoclonal Antibody (17A2), FITC, eBioscience TM Invitrogen, lot number: 11-0032-82, specification: 100ug / vial; CD45 Monoclonal Antibody (30-F11), PerCP-Cyanine 5.5, eBioscience TM Invitrogen, lot number: 45-0451-82, specification: 100ug / vial; CD8a Monoclonal Antibody (53-6.7), PE, eBioscience TM Invitrogen, lot number: 12-0081-82, specification: 100ug / vial; CD4 Monoclonal Antibody (RM4-5), APC, eBioscience TM Invitrogen, lot number: 17-0042-82, specification: 100ug / tube; LIVE / DEAD TM Fixable Dead Cell Stain Kits, Invitrogen, Lot No.: L10119, Specification: 100ug / kit;

[0101] 1.4 Instruments

[0102] Electronic balance (Sartorius Scientific Instruments, model BS224S); Low-temperature centrifuge (Eppendorf, Germany, model 5804R); Purified water system (Milli-QPlus, Germany); Animal weight scale (Shanghai Xiangchuan Electronic Weighing Instrument Co., Ltd., model CX-SC-DA); Microplate reader (McGen, USA, model Flexstation 3).

[0103] 2. Dosage design

[0104] The daily dosage of the traditional Chinese medicine composition is 46.04g of crude drug / day. Based on the body surface area calculation method, the equivalent dose for mice is 46.04g / 60kg × 12.3 = 9.43g crude drug / kg ≈ 9.4g crude drug / kg. Following a 1 / 4:1 / 2:1 dosing regimen, the low dose is 2.35g crude drug / kg, and the medium dose is 4.7g crude drug / kg. Administered by gavage, 0.2mL / 10g, once daily.

[0105] 3. Experimental Methods

[0106] Sixty healthy mice were randomly divided into six groups: a control group, a model group, low-, medium-, and high-dose groups of the traditional Chinese medicine composition, and a salbutamol injection group, with ten mice in each group. Except for the control group, a mouse model of chronic obstructive pulmonary disease (COPD) was established using passive smoking and lipopolysaccharide (LPS) induction. Mice were placed in a sealed smoke chamber measuring 65cm × 40cm × 25cm. Cigarettes were lit, and smoke was introduced into the chamber using an air pump, with the smoke equivalent of two cigarettes introduced at a time. Passive smoking lasted for 10 minutes, followed by a 10-minute rest period. This process was repeated four times, for a total of 50 minutes of passive smoking per day. Passive smoking was administered 6 days per week for 5 weeks. Simultaneously, on days 1, 14, and 34 of the smoking period, mice were anesthetized with 10% chloral hydrate, and 20 μg (30 μL) of LPS was instilled intratracheally. The model mice exhibited lethargy, dull and shedding fur, reduced movement, rapid breathing, and significant coughing, with a marked decrease in lung function, indicating successful model establishment. After successful modeling, the salbutamol injection group received an intraperitoneal injection of 0.4 mg salbutamol per dose (diluted with 20 mL of 5% glucose injection). The low, medium, and high dose groups of the traditional Chinese medicine composition were administered the drug by gavage according to the dosage settings, while the blank group and the model group were administered the same volume of physiological saline by gavage as the traditional Chinese medicine group.

[0107] 4. Statistical Methods

[0108] The results were statistically analyzed using t-tests.

[0109] 5. Experimental Results

[0110] 5.1 Blood CD3+, CD4+, and CD8+ levels in COPD mice

[0111] Compared with the control group, the blood CD3+ and CD4+ levels of mice in the model group decreased, while the CD8+ level increased (P < 0.001); compared with the model group, the blood CD3+ and CD4+ levels of mice in the positive control group, the experimental medium-dose group, and the experimental high-dose group all showed an increasing trend, while the CD8+ level showed a decreasing trend (P < 0.001); the results are shown in Table 3.

[0112] Table 3 Comparison of CD3+, CD4+, and CD8+ levels in the blood of mice in each group

[0113] Blank control group 10 87.68±3.94*** 70.16±2.71*** 20.87±3.00*** Model control group 10 60.53±2.23▲▲▲ 48.41±4.29▲▲▲ 37.25±3.35▲▲▲ Positive drug group 10 78.87±4.79*** 63.13±3.08*** 27.09±1.64*** low-dose group 10 60.95±2.43 52.83±2.37* 35.71±1.57 medium dose group 10 75.56±4.77*** 60.34±2.67*** 29.64±1.44*** High-dose group 10 81.35±5.74*** 67.02±4.06*** 25.95±1.19***

[0114] Note: Compared with the control group, ▲P<0.05, ▲▲P<0.01, ▲▲▲P<0.001; compared with the model control group, *P<0.05, **P<0.01, ***P<0.001.

[0115] 5.2 Effects on serum inflammatory factor levels in mice

[0116] Compared with the blank control group, the serum IL-1β level in the model group mice was significantly increased (P < 0.001). Compared with the model group, the serum IL-1β level in the positive control group, the high-dose group of the traditional Chinese medicine composition, and the medium-dose group of mice was significantly decreased (P < 0.01). The results are shown in Table 3.

[0117] Table 4 shows the effect of serum IL-1β levels in each group of mice.

[0118]

[0119]

[0120] Note: Compared with the control group, ▲P<0.05, ▲▲P<0.01, ▲▲▲P<0.001; compared with the model control group, *P<0.05, **P<0.01, ***P<0.001.

[0121] 6. Experimental Conclusions

[0122] The traditional Chinese medicine composition at 4.8 g crude drug / kg significantly improved lung FVC, FEV0.3, and PEF function in rats and significantly regulated the content of inflammatory factor IL-8 in rat serum. The traditional Chinese medicine composition at 9.4 g and 4.7 g crude drug / kg significantly increased the levels of CD3+ and CD4+ in mouse blood and significantly regulated the content of inflammatory factor IL-1β in mouse serum, maintaining the stability of the body's immune system. This suggests that the traditional Chinese medicine composition has a certain therapeutic effect on smoke fumigation combined with LPS-induced chronic obstructive pulmonary disease in mice and rats.

[0123] The above are merely preferred embodiments of the present invention. It should be noted that those skilled in the art can make various improvements and modifications without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. Application of traditional Chinese medicine compositions in the preparation of drugs for the prevention and treatment of chronic obstructive pulmonary disease; The traditional Chinese medicine composition is made from the following raw materials in parts by weight: 1-6 parts Magnolia biondii, 1-6 parts Perilla frutescens, 1-5 parts Schizonepeta tenuifolia, 1-5 parts Angelica dahurica, 1-5 parts Arctium lappa, 1-5 parts Xanthium sibiricum, 1-5 parts Schisandra chinensis, 1-6 parts Codonopsis pilosula, and 1-3 parts Glycyrrhiza uralensis.

2. The application according to claim 1, characterized in that, The prevention and treatment include: reducing cytokine levels and / or improving lung function.

3. The application according to claim 2, characterized in that, The cytokines include IL-8, CD3, CD4, or CD8.

4. The application according to claim 2, characterized in that, The improvement in lung function includes increasing FVC, FEV0.3, FEV0.3 / FVC and / or PEF levels.

5. The application according to any one of claims 1 to 4, characterized in that, The chronic obstructive pulmonary disease mentioned above is chronic obstructive pulmonary disease caused by harmful gases.

6. The application according to claim 5, characterized in that, The harmful gas is cigarette smoke.

7. The application according to claim 1, characterized in that, The preparation method of the traditional Chinese medicine composition includes: The magnolia flower, perilla leaf, schizonepeta, and cocklebur fruit were mixed, soaked in water, distilled, and the volatile oil was extracted. Then, the volatile oil inclusion complex was prepared for later use. The remaining residue was boiled again, filtered, and the resulting decoction was combined and concentrated to obtain thick paste I. The Codonopsis pilosula and Glycyrrhiza uralensis were mixed, decocted with water, filtered, and the resulting decoction was concentrated to obtain a thick paste II. The Angelica dahurica, Arctium lappa, and Schisandra chinensis were mixed and extracted by reflux with ethanol. The obtained ethanol extract was concentrated to obtain a thick paste III. After combining the three thick pastes I, II, and III, they were dried under reduced pressure and pulverized, and then the volatile oil inclusion complex was added and mixed evenly.

Images