Traditional Chinese medicine composition for preventing chronic obstructive pulmonary disease as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention relates to the technical field of traditional Chinese medicine, in particular to a traditional Chinese medicine composition for preventing and treating chronic obstructive pulmonary disease, which is prepared from the following medicinal raw materials: ginseng, poria cocos, rhizoma zingiberis, liquorice, fructus perillae, malt and pericarpium citri reticulatae. In the traditional Chinese medicine composition, the rhizoma zingiberis is used as a monarch for eliminating dampness, warming the middle warmer and purging water by banking up, the ginseng is used as a minister for tonifying qi and lung, the poria cocos, the pericarpium citri reticulatae, the perillaseed and the malt are used as assistants for strengthening and transporting the spleen and regulating and tonifying the lung, the honey-fried licorice root is used as a guide for regulating the middle warmer, lowering the stomach and harmonizing the medicines, and the medicines have a synergistic effect of tonifying qi, removing phlegm, tonifying the spleen and tonifying the lung. Under the two conditions of a COPD model mouse conventional replication method (in which lipopolysaccharide is dripped into a trachea to combine with cigarette smoking) and a plateau simulation cabin 3000-meter altitude to combine with cigarette smoking replication method, effective treatment effects can be generated in lung and intestine function repair, aiming at lung tissues, lung inflammation can be relieved, and the lung function of a COPD model mouse can be improved; by aiming at the repairable intestinal mucosal barrier of intestinal tissues, the immune function of a COPD model mouse can be improved, so that the COPD is improved.

Description

Technical Field

[0001] The present invention belongs to the field of medical technology, and in particular relates to a traditional Chinese medicine composition for preventing chronic obstructive pulmonary disease, and a preparation method and application thereof. Background Art

[0002] Chronic obstructive pulmonary disease (COPD) is a progressive airflow limitation characterized by abnormalities in airway and alveolar structure, leading to persistent dyspnea, chronic cough, sputum production, and recurrent acute exacerbations. Its primary pathological manifestations include chronic airway inflammation, emphysema caused by lung parenchymal destruction, and fibrotic remodeling of the small airways. Epidemiological data indicate that COPD is the third leading cause of death and the seventh leading cause of disability worldwide. The global death toll is projected to exceed 5.4 million by 2060, resulting in a significant medical and economic burden. The "China Adult Lung Health Study" survey revealed that the prevalence of COPD in adults aged 20 years and older is 8.6%, rising to 13.7% in those aged 40 and older. COPD is trending toward younger age and exhibits significant regional disparities, with the prevalence reaching as high as 20.2% in the southwestern plateau. This suggests that low oxygen, low pressure, and low temperatures at high altitudes serve as independent risk factors, exacerbating the disease by inducing chronic hypoxia, altering lung mechanical stress, and suppressing respiratory defenses.

[0003] The pathogenesis of COPD exhibits multidimensional characteristics, involving key pathological links such as the inflammatory cascade, imbalances in the protease-antiprotease system, and oxidative stress. Tobacco exposure, as the primary pathogenic factor, collaborates with occupational dust exposure and air pollution to trigger persistent airway inflammation, primarily characterized by neutrophil infiltration. Proinflammatory cytokines TNF-α, IL-6, and IL-8, through activation of signaling pathways such as NF-κB, promote inflammatory cell recruitment, enhance matrix metalloproteinase activity, and synergize with TGF-β to exacerbate airway remodeling, forming cross-regulatory interactions with type 2 inflammatory responses. Notably, inflammatory type 2 innate lymphocytes (iILC2s) exhibit cross-organ migration under the stimulation of the high-altitude environment. Intestinal iILC2s migrate to the lungs, exacerbating the Th2 immune response by releasing cytokines such as IL-5 and IL-13, creating a vicious cycle of inflammatory-immune interactions.

[0004] Traditional Chinese Medicine classifies COPD into the categories of "pulmonary distension," "cough," "asthma," and "phlegm and fluid retention." It is usually caused by the gradual worsening of chronic cough and asthma, with a slow onset. The disease is located in the lungs and affects the spleen and kidneys. Its pathogenesis is characterized by "fundamental deficiency and superficial excess, a mixture of deficiency and excess." It is based on Qi deficiency in the lungs, spleen, and kidneys, while symptoms include turbid phlegm, blood stasis, and fluid retention. "The spleen governs the four seasons" and is the intermediate link in lung dysfunction. Treating the lungs from the spleen can balance the functions of the internal organs. Prolonged coughs and sputum production, recurring asthma attacks, lung deficiency, and loss of Qi control lead to worsening shortness of breath and wheezing. The child steals the mother's Qi, the spleen is affected, and its transportation and transformation functions are impaired, resulting in endogenous phlegm. The spleen governs blood regulation, and long-term illness weakens the lungs, making them unable to assist the heart in blood circulation. Spleen deficiency fails to retain blood, and blood does not return to its normal path. Insufficient blood circulation leads to blood stasis. "The spleen is the source of phlegm, and the lungs are the reservoir of phlegm." The "Inner Canon of Medicine" states, "If the lungs are not injured, there will be no cough; if the spleen is not injured, there will be no cough soon." Abnormal spleen function can aggravate lung disease. According to Traditional Chinese Medicine, earth generates metal. The spleen belongs to earth, and the lungs belong to metal. The spleen is the mother of the lungs, and the lungs are the child of the spleen. Diseases of the child affect the mother. Choosing the method of nourishing earth to generate metal strengthens the spleen and lungs, replenishes qi and eliminates phlegm. By strengthening the spleen and nourishing the lungs, this method treats lung deficiency. A healthy spleen not only transfers sufficient water and grain essences to nourish the entire body but also promotes the production of lung qi, restoring lung function.

[0005] Current clinical treatments rely primarily on bronchodilators and glucocorticoids. While these can temporarily alleviate symptoms, long-term use can lead to β2 receptor desensitization, increased risk of fungal infections, and progressive lung function decline. In contrast, Traditional Chinese Medicine (TCM), through its multi-component, multi-target interventions, demonstrates unique value in improving airway remodeling and regulating immune imbalance, providing an important complementary strategy for the comprehensive management of COPD.

[0006] In addition, on the one hand, there are differences in understanding among those skilled in the art; on the other hand, the inventor studied a large number of documents and patents when making the present invention, but due to space limitations, not all details and contents are listed in detail. However, this does not mean that the present invention does not have the characteristics of these prior arts. On the contrary, the present invention already has all the characteristics of the prior art, and the applicant reserves the right to add relevant prior art to the background art. Summary of the Invention

[0007] The present invention aims to solve the problem of lung and intestinal inflammation and continuous decline in lung function in COPD patients, and provides a highly safe Chinese medicine composition and a preparation method thereof. Through reasonable formulation and compatibility, the modified Huangya decoction is verified under two conditions: a conventional replication method for COPD model mice (intratracheal instillation of lipopolysaccharide combined with cigarette fumigation) and a replication method at an altitude of 3,000 meters in a plateau simulation cabin combined with cigarette fumigation. The results show that the modified Huangya decoction can relieve collagen deposition in the small airways and improve lung inflammation in the lungs; and improve intestinal mucosal damage in the intestines, and reduce the content of pro-inflammatory factors in the lungs, serum, and colon, so as to achieve the effect of preventing and treating chronic obstructive pulmonary disease.

[0008] Based on the above technical problems, one of the objectives of the present invention is to provide a traditional Chinese medicine composition for preventing and treating chronic obstructive pulmonary disease, which comprises ginseng, dried ginger, Yun Fuling, roasted licorice, tangerine peel, malt and perilla seed.

[0009] According to a preferred embodiment, the Chinese medicine composition comprises the following raw materials by mass: 1-6 parts of ginseng, 0.5-3 parts of dried ginger, 2-10 parts of Yunfuling, 0.5-5 parts of roasted licorice root, 1-6 parts of dried tangerine peel, 2-10 parts of malt, and 0.5-5 parts of perilla seed. Preferably, the Chinese medicine composition comprises the following raw materials by mass: 3 parts of ginseng, 1 part of dried ginger, 5 parts of Yunfuling, 2 parts of roasted licorice root, 3 parts of dried tangerine peel, 5 parts of malt, and 2 parts of perilla seed.

[0010] According to a preferred embodiment, the pharmaceutical composition further comprises a pharmaceutically or culinarily acceptable carrier. The carrier is, for example, an additive. Preferably, the pharmaceutically or culinarily acceptable carrier comprises any one or more of a flavoring agent, a filler, a lubricant, a binder, a cross-linking agent, a pH adjuster, a humectant, a preservative, an antioxidant, or a solvent.

[0011] One of the objectives of the present invention is to provide the use of the above-mentioned Chinese medicine composition in the preparation of products for preventing, treating, alleviating or improving chronic obstructive pulmonary disease.

[0012] One of the purposes of the present invention is to provide the use of the above-mentioned Chinese medicine composition in the preparation of a product having the function of reducing the level of inflammation in the lungs, serum, and colon of humans or animals.

[0013] One of the purposes of the present invention is to provide the use of the above-mentioned traditional Chinese medicine composition in the preparation of a product having the function of repairing the intestinal microenvironment of humans or animals.

[0014] According to a preferred embodiment, the product is a food, a health product or a medicine.

[0015] According to a preferred embodiment, the product having the function of repairing the intestinal microenvironment of humans or animals can repair the intestinal mucosal barrier function of humans or animals.

[0016] According to a preferred embodiment, the product having the function of repairing the intestinal mucosal barrier of humans or animals can have the function of increasing the sIgA content in the lungs and colons of humans or animals.

[0017] According to a preferred embodiment, the product having the function of reducing the level of inflammation in human or animal serum can have the function of reducing the content of TNF-α in the lung, serum and colon of human or animal.

[0018] According to a preferred embodiment, the pharmaceutical composition is an oral preparation. Preferably, the oral preparation is a liquid dosage form, such as any one of pills, granules, pastes, powders, decoctions, capsules, and drop pills.

[0019] One of the objectives of the present invention is to provide a method for preparing a traditional Chinese medicine composition for preventing and treating chronic obstructive pulmonary disease, which comprises the following steps:

[0020] S1: decocting the raw materials of the above-mentioned Chinese medicine composition and cooling;

[0021] S2: The liquid medicine obtained in S1 is concentrated into a thick extract and stored in a -20°C refrigerator for later use.

[0022] Preferably, the extraction method in S1 is any one of decoction, maceration, percolation, reflux, solvent extraction, steam distillation, supercritical fluid extraction, ultrafine grinding technology, semi-bionic extraction, ultrasonic extraction, cyclone extraction or pressurized countercurrent extraction.

[0023] The beneficial effects of this technical solution are as follows:

[0024] The traditional Chinese medicine composition provided by the present invention is scientifically combined with seven medicinal and edible ingredients: ginseng, dried ginger, Yunfuling, roasted licorice root, tangerine peel, malt, and perilla seed. In this medicinal and edible composition, dried ginger acts as the main ingredient to dry dampness and warm the middle, nourish the earth and expel water, while ginseng acts as the auxiliary ingredient to tonify qi and benefit the lungs. Poria cocos, tangerine peel, perilla seed, and malt act as auxiliary ingredients to invigorate the spleen and nourish the lungs, while roasted licorice root acts to soothe the middle and soothe the stomach, harmonizing the other ingredients.

[0025] Chronic obstructive pulmonary disease (COPD) in Traditional Chinese Medicine (TCM) is classified as a condition characterized by pulmonary distension and other symptoms. It typically develops from chronic cough and asthma, which gradually worsens. The disease develops slowly, primarily in the lungs, but also affects the spleen and kidneys. Its pathogenesis is characterized by a mixture of deficiency and excess, with underlying qi deficiency and superficial excess. Qi deficiency in the lungs, spleen, and kidneys is the underlying cause, while phlegm, blood stasis, and fluid retention are the superficial symptoms. The spleen, known as "governing the four seasons," is the central link in lung dysfunction. Treating the lungs from the spleen can restore proper internal organ function. Prolonged cough and sputum production, along with recurrent asthma, indicate lung deficiency and a loss of qi control, leading to increased shortness of breath and wheezing. The spleen, like the child stealing the mother's qi, impairs its transport and transformation functions, resulting in the internal production of phlegm. The spleen regulates blood flow, and chronic illness weakens the lungs, making them unable to assist the heart in blood circulation. This weakened spleen fails to retain blood, leading to abnormal blood circulation and stasis. "The spleen is the source of phlegm, and the lungs are the reservoir of phlegm," states the Neijing (Inner Canon of Medicine). "Uninjured lungs prevent coughing, and uninjured spleens prevent coughing soon." Abnormal spleen function can exacerbate lung disease. According to Traditional Chinese Medicine, earth generates metal. The spleen belongs to earth, and the lungs belong to metal. The spleen is the mother of the lungs, and the lungs are the child of the spleen. Diseases of the child affect the mother. Choosing the method of nourishing earth to generate metal strengthens the spleen and lungs, replenishes qi and eliminates phlegm. By strengthening the spleen and nourishing the lungs, this method treats lung deficiency. A healthy spleen not only transfers sufficient water and grain essences to nourish the entire body, but also promotes the production of lung qi, restoring lung function.

[0026] The medicinal and edible combination provided by the present invention regulates the middle earth, prevents and treats COPD, and strengthens the spleen and lungs, replenishing qi and eliminating phlegm. In this Chinese medicine composition, ginseng significantly replenishes vital energy; licorice harmonizes the middle, treating the spleen and stomach, and aiding their ascending and descending functions; raw malt promotes qi, strengthens the spleen, and stimulates appetite, treating the stomach and aiding its descent; it also soothes the liver and relieves depression, thereby promoting the growth of wood energy; Yunfuling strengthens the spleen and eliminates dampness, treating the spleen and aiding its ascent; and dried ginger dries dampness and warms the middle, promoting stagnation and descending turbidity, nourishing fire and earth, and warming the middle earth. This allows the middle qi to properly mediate, allowing the lung metal to descend and transform water, thus preventing the production of phlegm. The five herbs work in harmony to regulate the acquired spleen and stomach, supporting the production of qi and blood, thereby strengthening the body's internal energy and suppressing pathogenic factors. Furthermore, tangerine peel and perilla seed are combined to clear the lungs, regulate qi, resolve phlegm, and alleviate adverse reactions. The seven herbs work together to strengthen the spleen and soothe the liver, clear and descend the lungs and stomach, and harmonize the upper and lower parts of the body. This results in the stomach descending and improving absorption, the spleen ascending and improving digestion, the liver ascending and relieving blood stagnation, the lung descending and relieving qi stagnation, and the heart and kidney harmonizing (water and fire complementing each other). This agent can both descend the lungs and stomach on the right and ascend the liver and spleen on the left, acting as a clear-lifting and turbid-lowering agent. By "tonifying qi and resolving phlegm, strengthening the spleen and benefiting the lungs," it can effectively repair the intestinal microenvironment and reduce lung inflammation, providing a safe and effective clinical combination. While preventing, alleviating, or improving chronic obstructive pulmonary disease, it also reduces inflammation levels in the lungs, serum, and colon of humans or animals and improves the intestinal microenvironment, playing a preventive role in chronic obstructive pulmonary disease.

[0027] Compared with traditional treatment options, the technological breakthroughs of this invention are: 1) It pioneered the integration of the triple action mechanism of "strengthening the spleen and lungs - soothing the liver and stomach - resolving phlegm and removing blood stasis", inhibiting fibroblast activation by regulating the TGF-β1 pathway, and simultaneously improving airway remodeling and lung function; 2) Establishing a new intervention model based on the regulation of the "lung-gut axis", improving systemic inflammation by regulating iILC2 differentiation; 3) Using all medicinal and edible components to construct a "treatment and nourishment combined" system. Long-term use can maintain serum sIgA levels within the normal range, avoiding the risk of immunosuppression caused by glucocorticoids, and fully reflecting the safe and effective prevention and treatment characteristics of traditional Chinese medicine. In clinical applications, traditional Chinese medicine can significantly improve patients' immune function, slow down the downward trend of lung function, and improve quality of life through methods such as cultivating the soil to produce gold, strengthening the spleen and kidneys, and nourishing qi and yin. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 The present invention is to show the effect of the modified Huangya decoction on the pathological changes of lung tissue in COPD model mice (intratracheal instillation of lipopolysaccharide combined with cigarette smoking) (HE staining), wherein the blank group is Normal, the model group is COPD, the blank group is Normal, the model group is COPD, the high-dose modified Huangya decoction group is COPD+JHD-H, the medium-dose modified Huangya decoction group is COPD+JHD-M, and the low-dose modified Huangya decoction group is COPD+JHD-L;

[0029] Figure 2The present invention is to show the effect of the modified Huangya decoction on the pathological changes of lung tissue in COPD model mice (intratracheal instillation of lipopolysaccharide combined with cigarette smoking) (Masson staining), wherein the blank group is Normal, the model group is COPD, the blank group is Normal, the model group is COPD, the high-dose modified Huangya decoction group is COPD+JHD-H, the medium-dose modified Huangya decoction group is COPD+JHD-M, and the low-dose modified Huangya decoction group is COPD+JHD-L;

[0030] Figure 3 The present invention is to show the effect of the modified Huangya decoction on the pathological changes of colon tissue in COPD model mice (intratracheal instillation of lipopolysaccharide combined with cigarette smoking) (HE staining), wherein the blank group is Normal, the model group is COPD, the high-dose modified Huangya decoction group is COPD+JHD-H, the medium-dose modified Huangya decoction group is COPD+JHD-M, and the low-dose modified Huangya decoction group is COPD+JHD-L;

[0031] Figure 4 The present invention is to improve the effect of the modified Huangya decoction on the pathological changes of lung tissue in COPD model mice (high altitude simulation cabin combined with cigarette smoking) (HE staining), wherein the blank group is Normal, the model group is COPD, the high-dose modified Huangya decoction group is COPD+JHD-H, the medium-dose modified Huangya decoction group is COPD+JHD-M, and the low-dose modified Huangya decoction group is COPD+JHD-L;

[0032] Figure 5 The present invention shows the effect of the modified Huangya decoction on the pathological changes of lung tissue in COPD model mice (high altitude simulation cabin combined with cigarette smoking) (Masson staining), wherein the blank group is Normal, the model group is COPD, the high-dose modified Huangya decoction group is COPD+JHD-H, the medium-dose modified Huangya decoction group is COPD+JHD-M, and the low-dose modified Huangya decoction group is COPD+JHD-L;

[0033] Figure 6 This is the effect of the modified Huangya decoction of the present invention on the pathological changes of colon tissue in COPD model mice (high altitude simulation cabin combined with cigarette smoking) (HE staining), wherein, the blank group: Normal, the model group: COPD, the high-dose modified Huangya decoction group: COPD+JHD-H, the medium-dose modified Huangya decoction group: COPD+JHD-M, and the low-dose modified Huangya decoction group: COPD+JHD-L. DETAILED DESCRIPTION

[0034] In the description of the present invention, terms are used for descriptive purposes only and should not be understood to indicate or imply relative importance or implicitly indicate the number of technical features indicated. In the description of the present invention, "plurality" means two or more, unless otherwise specifically defined.

[0035] Unless otherwise specified, the test methods used in the following examples are all conventional methods; the materials, reagents or instruments used without indicating the manufacturer are all reagents and materials that can be obtained from commercial channels; if no specific conditions are specified in the examples, they are all carried out according to conventional conditions or conditions recommended by the manufacturer. At the same time, the present invention does not limit the sources of the raw materials used. Unless otherwise specified, the raw materials used in the present invention are all common commercial products in this technical field.

[0036] In this application, high heat and low heat are conventional techniques for decocting Chinese medicine. High heat: large flame and high temperature (rapid temperature rise), suitable for rapid boiling or short-term decoction. Low heat: small flame and low temperature (slow temperature rise), suitable for maintaining a slight boil and long-term decoction.

[0037] Example 1

[0038] This embodiment provides a traditional Chinese medicine composition and a preparation method thereof, which specifically includes the following medicinal raw materials by weight:

[0039] 3 parts of ginseng, 1 part of dried ginger, 5 parts of Yunfuling, 2 parts of roasted liquorice root, 3 parts of dried tangerine peel, 5 parts of malt, and 2 parts of perilla seeds.

[0040] The method for preparing a decoction of a Chinese medicine composition comprises the following steps:

[0041] The medicinal raw materials are weighed according to the above ratio, and are soaked in deionized water 10 to 15 times the volume of the medicinal raw materials for half an hour. The water is boiled over high heat, then simmered over low heat for 30 minutes. After decocting, the medicinal residue is filtered through gauze, and the medicinal residue is returned to the pot and decocted again twice. During the second decoction, 10 times the volume of deionized water of the medicinal residue is added, and the water is boiled over high heat, then simmered over low heat for 30 minutes, and the filtrate is taken. During the third decoction, 8 times the volume of deionized water of the medicinal residue is added, and the water is boiled over high heat, then simmered over low heat for 30 minutes, and the filtrate is filtered and taken. The filtrates obtained after the three decoctions are combined to obtain a medicinal solution, which is cooled.

[0042] Example 2

[0043] This embodiment provides a traditional Chinese medicine composition and a preparation method thereof, which specifically includes the following medicinal raw materials by weight:

[0044] 3 parts of ginseng, 1 part of dried ginger, 5 parts of Yunfuling, 2 parts of roasted liquorice root, 3 parts of dried tangerine peel, 5 parts of malt, and 2 parts of perilla seeds.

[0045] The method for preparing a decoction of a Chinese medicine composition comprises the following steps:

[0046] S1: Weigh the drug raw materials according to the above ratio, and prepare and cool them according to the method of Example 1;

[0047] S2: The liquid medicine obtained in S1 is further concentrated by using a rotary evaporator for reduced pressure rotary evaporation. The specific operation is as follows: the cooled liquid is poured into the rotary evaporation bottle in several times. The liquid poured in each time cannot exceed one third of the total volume of the rotary evaporation bottle. The rotary evaporation temperature is controlled at 42°C, the rotation speed is adjusted to gear 4, the atmospheric pressure is first adjusted to 80 atmospheres, and after the rotary evaporation starts, the atmospheric pressure is reduced as needed until it is concentrated into a viscous, nearly paste-like liquid. The above-mentioned viscous, nearly paste-like liquid is poured into glass containers and divided into portions for use.

[0048] Example 3

[0049] In this example, the medicinal and edible composition prepared in Example 2 was used to verify its efficacy and study its mechanism.

[0050] 1. Verification of respiratory system function restoration in normal pressure environment

[0051] 1. Materials and Methods

[0052] C57BL / 6, 6-8 week old males weighing 19-23 g were used as experimental animals and randomly divided into a blank group (Normal), a model group (COPD), a high-dose Jiawei Huangya Decoction (JHD) group (COPD+JHD-H), a medium-dose Jiawei Huangya Decoction group (COPD+JHD-M), and a low-dose Jiawei Huangya Decoction group (COPD+JHD-L) according to the experimental needs. The drugs administered to the high-dose group, medium-dose group, and low-dose group were all prepared according to the component composition and preparation method of Example 1. The medium dose was a clinically equivalent dose. The dosages of the high-dose group, medium-dose group, and low-dose group were 16.38 g / kg, 8.19 g / kg, and 4.1 g / kg, respectively. The blank group and model group were gavaged with equal amounts of sterile distilled water.

[0053] COPD mouse models were established using intratracheal instillation of lipopolysaccharide (LPS) combined with cigarette smoke. Except for the blank group, all other mice received intratracheal LPS injections on days 1 and 14. From day 2 to 84 (except the day of LPS instillation), mice were smoked for 40 minutes daily. Starting on day 85, the mice were smoked every other day for 40 minutes daily. The experiment ended on day 112. During the COPD model establishment process, COPD+JHD-H, COPD+JHD-M, and COPD+JHD-L were administered starting on day 28. The blank and model groups received equal amounts of sterile distilled water orally once daily until the end of the experiment.

[0054] Clinically, COPD is often diagnosed as a ratio of forced expiratory volume in one second to forced vital capacity (FEV1 / FVC) less than 70% after inhalation of a bronchodilator. Lung function indicators are important indicators of incompletely reversible airflow limitation. Therefore, in an animal model established by intratracheal instillation of lipopolysaccharide combined with cigarette smoke, forced expiratory volume in 84 milliseconds (FEV84), FVC, FEV84 / FVC, and maximal mid-expiratory flow (MMEF) were selected based on the lung function test results of mice in the control group. FVC, FEV84, FEV84 / FVC, and MMEF decrease in airflow limitation. MMEF, a marker of lung diffusion capacity, indicates decreased vital capacity and altered lung volume due to small airway obstruction.

[0055] Table 1 shows the effects of the Chinese herbal composition of the present invention on the lung function of COPD model mice (intratracheal instillation of lipopolysaccharide combined with cigarette smoking).

[0056] Table 1 shows the effects of a traditional Chinese medicine composition for preventing and treating chronic obstructive pulmonary disease on the lung function of COPD model mice (intratracheal instillation of lipopolysaccharide combined with cigarette smoking) (n=6, x±s).

[0057] Table 1

[0058] Group FVC FEV50 FEV50 / FVC MMEF Normal 0.71±0.06 0.62±0.03 0.87±0.07 14.6±1.04 COPD <![CDATA[0.56±0.06 # ]]> <![CDATA[0.4±0.04 # ]]> <![CDATA[0.73±0.13 # ]]> <![CDATA[12.39±0.81 # ]]> COPD+JHD-H 0.65±0.07* 0.54±0.04* 0.84±0.07* 13.86±0.73* COPD+JHD-M 0.66±0.05* 0.54±0.05* 0.83±0.05* 14.03±0.46* COPD+JHD-L 0.64±0.05* 0.61±0.02* 0.95±0.08* 13.54±0.95*

[0059] Note: # P (compared with the blank group P < 0.05), * P (compared with the model group P < 0.05). Blank group: Normal, model group: COPD, high-dose modified Huangya decoction group: COPD + JHD-H, medium-dose modified Huangya decoction group: COPD + JHD-M, low-dose modified Huangya decoction group: COPD + JHD-L.

[0060] The lung function of COPD mice modeled by intratracheal instillation of lipopolysaccharide combined with cigarette smoking decreased in FVC, FEV84, FEV84 / FVC, and MMEF (P<0.05), which were statistically different from those in the blank group. After intervention with each dose of Jiawei Huangya Decoction, the lung function of mice changed as follows: FVC increased in the high and low doses of Jiawei Huangya Decoction groups (P<0.05), which were statistically different from those in the model group. FVC in the medium dose of Jiawei Huangya Decoction group showed an upward trend (P >0.05), which had no statistical difference compared with the model group; FEV84 in the high, medium and low doses of Modified Huangya Decoction were all increased (P<0.05), which had statistical difference compared with the model group; FEV84 / FVC and MMEF in the high and medium doses of Modified Huangya Decoction were all increased (P<0.05), which had statistical difference compared with the model group; FEV84 / FVC and MMEF in the low dose of Modified Huangya Decoction group showed an upward trend (P>0.05), which had no statistical difference compared with the model group.

[0061] Microscopic observation of lung tissue HE staining can detect the alveolar morphology, inflammatory cell infiltration, etc. of mouse lung tissue.

[0062] The effect of the Chinese medicine composition of the present invention on the lung tissue of COPD model mice (intratracheal instillation of lipopolysaccharide combined with cigarette smoke) is shown in the following test results: Figure 1 shown.

[0063] HE staining results of lung tissues of COPD model mice replicated by intratracheal instillation of lipopolysaccharide combined with cigarette smoke showed that: COPD model mice had obvious inflammatory cell infiltration around the small airways, thickening of the small airway walls, narrowing of the lumen, disordered arrangement of epithelial cells, and partial fusion of alveoli; after intervention with various dose groups of Jiawei Huangya Decoction, the inflammatory infiltration around the small airways of COPD model mice was reduced and the small airway structure was improved.

[0064] Masson staining of lung tissue under a microscope can detect fibrin deposition in the lung parenchyma and respiratory tract of mice, which is used to compare lung pathological changes and assess the severity of fibrosis. Collagen fibers appear blue.

[0065] The effect of the Chinese medicine composition of the present invention on the lung tissue of COPD model mice (intratracheal instillation of lipopolysaccharide combined with cigarette smoke) is shown in the following test results: Figure 2 shown.

[0066] The results of Masson staining of lung tissues of COPD model mice replicated by intratracheal instillation of lipopolysaccharide combined with cigarette smoking showed that collagen deposition around the small airways of COPD model mice increased; after intervention in all dose groups of Jiawei Huangya Decoction, collagen deposition around the small airways was less than that in the model group.

[0067] TGF-β1 can inhibit the proliferation of multiple cells and induce epithelial cell apoptosis, while at the same time inducing the proliferation of mesenchymal-like cells and differentiation into myofibroblasts to promote wound healing and tissue fibrosis formation. Studies have shown that TGF-β1 is considered to be the most important molecule of pro-fibrotic growth factors in the body. TGF-β1 can activate fibroblasts in vitro, and overexpression in vivo can cause continuous fibrosis of the lungs.

[0068] Table 2 shows the effect of the Chinese herbal composition of the present invention on TGF-β1 in the small airways of COPD model mice (intratracheal instillation of lipopolysaccharide combined with cigarette smoking).

[0069] Table 2 shows the effect of a traditional Chinese medicine composition for preventing and treating chronic obstructive pulmonary disease on the expression level of TGF-β1 protein in the small airways of COPD model mice (intratracheal instillation of lipopolysaccharide combined with cigarette smoking) (n=3, x±s).

[0070] Table 2

[0071] Group TGF-β1 / β-actin Normal 0.77±0.27 COPD <![CDATA[1.5±0.35 # ]]> COPD+JHD-H 1.04±0.14 COPD+JHD-M 0.74±0.28* COPD+JHD-L 0.75±0.25*

[0072] Note: # P (compared with the blank group P < 0.05), * P (compared with the model group P < 0.05). Blank group: Normal, model group: COPD, blank group: Normal, model group: COPD, high-dose modified Huangya decoction group: COPD + JHD-H, medium-dose modified Huangya decoction group: COPD + JHD-M, low-dose modified Huangya decoction group: COPD + JHD-L.

[0073] The expression level of TGF-β1 protein in COPD model mice replicated by intratracheal instillation of lipopolysaccharide combined with cigarette smoking increased (P<0.05), which was statistically different from the blank group; after intervention with each dose group of Jiawei Huangya Decoction, the changes in TGF-β1 protein expression levels were as follows: the expression levels of TGF-β1 protein in the medium and low dose groups of Jiawei Huangya Decoction decreased (P<0.05), which was statistically different from the model group; the expression level of TGF-β1 protein in the high dose group of Jiawei Huangya Decoction showed a downward trend (P>0.05) and had no statistical difference compared with the model group.

[0074] Microscopic observation of colon tissue HE staining can detect the crypt depth and villus height in mouse colon tissue.

[0075] The effect of the Chinese medicine composition of the present invention on the colon tissue of COPD model mice (intratracheal instillation of lipopolysaccharide combined with cigarette smoke) is shown in the following test results: Figure 3 shown.

[0076] The results of HE staining of the colon tissue of COPD model mice replicated by intratracheal instillation of lipopolysaccharide combined with cigarette smoke showed that the basal layer of the colon of COP model mice was thinned, inflammatory infiltration was obvious, and the crypts were twisted and irregularly arranged; after intervention in the various dose groups of Jiawei Huangya Decoction, the basal layer of the colon tissue of the mice was smooth and intact, the crypts were clearly arranged and neatly arranged, and the inflammatory infiltration was reduced. Figure 3 .

[0077] TNF-α is mainly produced by monocytes and macrophages and can be produced in response to hypoxia, infection, and stimulation by harmful particles in the airways. It can stimulate epithelial cells to express a variety of adhesion molecules, thereby mediating the adhesion of leukocytes to vascular endothelial cells and increasing airway hyperresponsiveness.

[0078] The effects of the Chinese medicinal composition of the present invention on the pro-inflammatory factor TNF-α in serum, lung tissue and colon tissue of COPD model mice (intratracheal instillation of lipopolysaccharide combined with cigarette smoke) are shown in Table 3.

[0079] Table 3 shows the effects of a Chinese medicine composition for preventing and treating chronic obstructive pulmonary disease on the pro-inflammatory factor TNF-α in serum, lung tissue and colon tissue of COPD model mice (intratracheal instillation of lipopolysaccharide combined with cigarette smoke) (n=6, x±s).

[0080] Table 3

[0081]

[0082]

[0083] Note: #P (compared with the blank group, P < 0.05), *P (compared with the model group, P < 0.05). Blank group: Normal, Model group: COPD, High-dose Modified Huangya Decoction group: COPD + JHD-H, Medium-dose Modified Huangya Decoction group: COPD + JHD-M, Low-dose Modified Huangya Decoction group: COPD + JHD-L.

[0084] The inflammatory factor TNF-α in the serum, lung tissue and colon tissue of mice with COPD model established by intratracheal instillation of lipopolysaccharide combined with cigarette smoking increased (P<0.05), which was statistically different from the blank group; after intervention with different doses of modified Huangya decoction, the changes in the inflammatory factor TNF-α in the serum, lung tissue and colon tissue of mice were as follows: the serum pro-inflammatory factor TNF-α in the high, medium and low dose groups of modified Huangya decoction decreased (P<0.05), which was statistically different from the model group; the pro-inflammatory factor TNF-α in the lung tissue of the high, medium and low dose groups of modified Huangya decoction decreased (P<0.05), which was statistically different from the model group; the pro-inflammatory factor TNF-α in the colon tissue of the high, medium and low dose groups of modified Huangya decoction decreased (P<0.05), which was statistically different from the model group.

[0085] 2. Verification of respiratory system function repair in plateau simulated environment

[0086] 1. Materials and Methods

[0087] C57BL / 6 males, 6-8 weeks old, weighing 19-23g, were used as experimental animals and randomly divided into a blank group (Normal), a model group (COPD), a high-dose modified Huangya decoction group (COPD+JHD-H), a medium-dose modified Huangya decoction group (COPD+JHD-M), and a low-dose modified Huangya decoction group (COPD+JHD-L). The high-dose, medium-dose, and low-dose groups were administered with 16.38g / kg, 8.19g / kg, and 4.1g / kg, respectively. The blank and model groups were gavaged with an equal volume of sterile distilled water.

[0088] A COPD model was established in mice using a combination of a high-altitude simulation chamber and cigarette fumigation. The mice were placed in a sealed, homemade fumigation chamber and infused with cigarette smoke for one hour daily. Chronic hypobaric hypoxia was simulated using a hypobaric oxygen chamber (XF-3CL) to simulate an altitude of 3,000 meters, with an atmospheric pressure of 70.73 kPa, an oxygen partial pressure of 13.61 kPa, and an oxygen content of 209.63 g / m 3 Control temperature: 18±4℃, humidity: 60%±10%, air flow: 0.09~0.10m 3 / h. Except for the blank group, the oxygen content in the model group and the modified Huangya decoction (high, medium, and low dose groups) was gradually reduced to the designed value after entering the chamber. 6 hours / day. Modeling was carried out 6 days a week for 4 consecutive weeks.

[0089] COPD is often diagnosed clinically based on a ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1 / FVC) less than 70% after inhalation of a bronchodilator. Lung function indicators are important indicators of incompletely reversible airflow limitation. Therefore, in an animal model established by intratracheal instillation of lipopolysaccharide combined with cigarette smoke, forced expiratory volume in 50 milliseconds (FEV50), FVC, FEV50 / FVC, and MMEF were selected based on the lung function test results of mice in the control group. MMEF is a measure of lung diffusion function; a decrease in MMEF indicates decreased vital capacity and changes in lung volume caused by small airway obstruction.

[0090] Table 4 shows the effects of the Chinese herbal composition of the present invention on the lung function of COPD model mice (altitude simulation cabin combined with cigarette smoke).

[0091] Table 4 shows the effects of a traditional Chinese medicine composition for preventing and treating chronic obstructive pulmonary disease on the lung function of COPD model mice (altitude simulation cabin combined with cigarette smoking) (n=6, x±s).

[0092] Table 4

[0093] Group FVC FEV50 FEV50 / FVC MMEF Normal 0.71±0.06 0.62±0.03 0.87±0.07 14.6±1.04 COPD <![CDATA[0.56±0.06 # ]]> <![CDATA[0.4±0.04 # ]]> <![CDATA[0.73±0.13 # ]]> <![CDATA[12.39±0.81 # ]]> COPD+JHD-H <![CDATA[0.65±0.07 * ]]> <![CDATA[0.54±0.04 * ]]> <![CDATA[0.84±0.07 * ]]> <![CDATA[13.86±0.73 * ]]> COPD+JHD-M <![CDATA[0.66±0.05 * ]]> <![CDATA[0.54±0.05 * ]]> <![CDATA[0.83±0.05 * ]]> <![CDATA[14.03±0.46 * ]]> COPD+JHD-L <![CDATA[0.64±0.05 * ]]> <![CDATA[0.61±0.02 * ]]> <![CDATA[0.95±0.08 * ]]> <![CDATA[13.54±0.95 * ]]>

[0094] Note: # P (compared with the blank group P < 0.05), * P (compared with the model group P < 0.05). Blank group: Normal, model group: COPD, high-dose modified Huangya decoction group: COPD + JHD-H, medium-dose modified Huangya decoction group: COPD + JHD-M, low-dose modified Huangya decoction group: COPD + JHD-L.

[0095] The FVC, FEV50, FEV50 / FVC, and MMEF of COPD model mice replicated by the plateau simulation cabin combined with cigarette smoking were decreased (P<0.05), which were statistically different from the blank group; after intervention with different doses of modified Huangya decoction, the changes in FVC, FEV50, FEV50 / FVC, and MMEF of mice were as follows: FVC, FEV50, FEV50 / FVC, and MMEF of the high, medium, and low dose groups of modified Huangya decoction were increased (P<0.05), which were statistically different from the model group; FVC, FEV50, and FEV50 / FVC of the positive control butyric acid group were increased (P<0.05), which were statistically different from the model group, and MMEF of the positive control butyric acid group showed an upward trend (P>0.05), which was not statistically different from the model group.

[0096] Microscopic observation of lung tissue HE staining can detect the alveolar morphology, inflammatory cell infiltration, etc. of mouse lung tissue.

[0097] The effect of the Chinese medicine composition of the present invention on the lung tissue of COPD model mice (altitude simulation cabin combined with cigarette smoke) is shown in the following test results: Figure 4 shown.

[0098] HE staining results of lung tissues of COPD model mice replicated by plateau simulation cabin combined with cigarette smoke showed that: the inflammatory cell infiltration around the small airways of COP model mice was obvious, the small airway walls were thickened, the lumen was narrowed, the epithelial cells were disordered, and some alveoli were fused; after intervention with each dose group of Jiawei Huangya Decoction, the inflammatory infiltration around the small airways of COPD model mice was reduced, and the small airway structure was improved. Figure 4 .

[0099] Masson staining of lung tissue under a microscope can detect fibrin deposition in the lung parenchyma and respiratory tract of mice, which is used to compare lung pathological changes and assess the severity of fibrosis. Collagen fibers appear blue.

[0100] The effect of the Chinese medicine composition of the present invention on the lung tissue of COPD model mice (altitude simulation cabin combined with cigarette smoke) is shown in the following test results: Figure 5 shown.

[0101] The results of Masson staining of lung tissues of COPD model mice replicated by the plateau simulation cabin combined with cigarette smoking showed that the collagen deposition around the small airways of COPD model mice increased; after intervention in the various dose groups of Jiawei Huangya Decoction, the collagen deposition around the small airways was less than that in the model group. Figure 5 .

[0102] TGF-β1 can inhibit the proliferation of multiple cells and induce epithelial cell apoptosis, while at the same time inducing the proliferation of mesenchymal-like cells and differentiation into myofibroblasts to promote wound healing and tissue fibrosis formation. Studies have shown that TGF-β1 is considered to be the most important molecule of pro-fibrotic growth factors in the body. TGF-β1 can activate fibroblasts in vitro, and overexpression in vivo can cause continuous fibrosis of the lungs.

[0103] Table 5 shows the test results of the effect of the Chinese herbal composition of the present invention on TGF-β1 in the small airways of COPD model mice (altitude simulation cabin combined with cigarette smoking).

[0104] Table 5 shows the effect of a traditional Chinese medicine composition for preventing and treating chronic obstructive pulmonary disease on the expression level of TGF-β1 protein in the small airways of COPD model mice (altitude simulation cabin combined with cigarette smoking) (n=3, x±s).

[0105] Table 5

[0106]

[0107]

[0108] Note: # P (compared with the blank group P < 0.05), * P (compared with the model group P < 0.05). Blank group: Normal, model group: COPD, blank group: Normal, model group: COPD, high-dose modified Huangya decoction group: COPD + JHD-H, medium-dose modified Huangya decoction group: COPD + JHD-M, low-dose modified Huangya decoction group: COPD + JHD-L.

[0109] The expression level of TGF-β1 protein in COPD model mice established by the plateau simulation cabin combined with cigarette smoking was increased (P<0.05), which was statistically different from the blank group; after intervention with each dose group of Modified Huangya Decoction, the changes in TGF-β1 protein expression level were as follows: the expression levels of TGF-β1 protein in the high, medium and low dose groups of Modified Huangya Decoction were decreased (P<0.05), which was statistically different from the model group.

[0110] Microscopic observation of colon tissue HE staining can detect the crypt depth and villus height in mouse colon tissue.

[0111] The effect of the Chinese medicine composition of the present invention on the colon tissue of COPD model (altitude simulation cabin combined with cigarette smoke) mice, the test results are as follows Figure 6 shown.

[0112] The results of HE staining of the colon tissue of COPD model mice established by the plateau simulation cabin combined with cigarette smoke showed that the basal layer of the colon of COPD model mice was thinned, inflammatory infiltration was obvious, and the crypts were twisted and irregularly arranged; after intervention in the various dose groups of Jiawei Huangya Decoction, the basal layer of the colon tissue of the mice was smooth and intact, the crypts were clearly arranged and neatly arranged, and the inflammatory infiltration was reduced. Figure 6 .

[0113] TNF-α is mainly produced by monocytes and macrophages and can be produced in response to hypoxia, infection, and stimulation by harmful particles in the airways. It can stimulate epithelial cells to express a variety of adhesion molecules, thereby mediating the adhesion of leukocytes to vascular endothelial cells and increasing airway hyperresponsiveness.

[0114] Table 6 shows the effects of the Chinese herbal composition of the present invention on the expression levels of the pro-inflammatory factor TNF-α in serum, lung tissue, and colon tissue of COPD model mice (altitude simulation cabin combined with cigarette smoking).

[0115] Table 6 shows the effects of a traditional Chinese medicine composition for preventing and treating chronic obstructive pulmonary disease on the pro-inflammatory factor TNF-α in serum, lung tissue and colon tissue of COPD model mice (high altitude simulation cabin combined with cigarette smoking) (n=6, x±s).

[0116] Table 6

[0117]

[0118] Note: # P (compared with the blank group P < 0.05), * P (compared with the model group P < 0.05). Blank group: Normal, model group: COPD, high-dose modified Huangya decoction group: COPD + JHD-H, medium-dose modified Huangya decoction group: COPD + JHD-M, low-dose modified Huangya decoction group: COPD + JHD-L.

[0119] The inflammatory factor TNF-α in the serum, lung tissue and colon tissue of COPD model mice replicated by the plateau simulation cabin combined with cigarette smoking increased (P<0.05), which was statistically different from the blank group; after intervention with different doses of modified Huangya Decoction, the changes in the inflammatory factor TNF-α in the serum, lung tissue and colon tissue of mice were as follows: the inflammatory factor TNF-α in the serum, lung tissue and colon tissue of the medium-dose modified Huangya Decoction group decreased (P<0.05), which was statistically different from the model group; the serum TNF-α in the high-dose modified Huangya Decoction group decreased (P<0.05), which was statistically different from the model group, and the TNF-α in the lung and colon tissues of the high-dose modified Huangya Decoction group showed a downward trend (P>0.05), which was not statistically different from the model group; the TNF-α in the lung and colon tissues of the low-dose modified Huangya Decoction group decreased (P<0.05), which was statistically different from the model group, and the serum TNF-α in the low-dose modified Huangya Decoction group showed a downward trend (P>0.05), which was not statistically different from the model group.

[0120] iILC2 may play a key role in the immune-inflammatory imbalance in COPD. Under pathological conditions, iILC2 can be transferred to distant organs through the blood. For example, iILC2 in the intestine can transfer to the lungs through the gut-lung axis in response to inflammatory signals.

[0121] Table 7 shows the effects of the Chinese herbal composition of the present invention on the content of lung tissue and colon tissue in COPD model mice (altitude simulation cabin combined with cigarette smoke).

[0122] Table 7 shows the effects of a traditional Chinese medicine composition for preventing and treating chronic obstructive pulmonary disease on iILC2 in lung tissue of COPD model mice (high altitude simulation cabin combined with cigarette smoke) (n=4, x±s).

[0123] Table 7

[0124] Group Lung tissue iILC2 (%) Colon tissue iILC2 (%) Normal 59.5±0.71 57.95±4.21 COPD <![CDATA[61.4±0.67 # ]]> <![CDATA[65.03±1.59 # ]]> COPD+JHD-M <![CDATA[56.65±0.8 * ]]> <![CDATA[55.9±4.34 * ]]>

[0125] Note: # P (compared with the blank group P < 0.05), * P (P<0.05 compared with the model group).Blank group: Normal, model group: COPD, medium-dose modified Huangya decoction group: COPD+JHD-M.

[0126] The number of iILC2 cells in the lung and colon tissues of COPD model mice replicated by the plateau simulation cabin combined with cigarette fumigation increased (P<0.05), which was statistically different from the blank group; after intervention with modified Huangya Decoction, the changes in the number of iILC2 cells in the lung and colon tissues of mice were as follows: the number of iILC2 cells in the lung and colon tissues of the medium-dose modified Huangya Decoction group decreased (P<0.05), which was statistically different from the model group.

[0127] It should be noted that the above-described specific embodiments are illustrative only. Those skilled in the art may devise various solutions based on the disclosure of the present invention, and such solutions fall within the scope of the present invention and are intended to be protected by the present invention. Those skilled in the art should understand that the present description and its accompanying drawings are intended to be illustrative only and are not intended to limit the scope of the claims. The scope of protection of the present invention is defined by the claims and their equivalents.

Claims

1. A Chinese medicine composition for preventing and treating chronic obstructive pulmonary disease, characterized in that: The invention comprises 1-6 parts of ginseng, 0.5-3 parts of dried ginger, 2-10 parts of Yunfuling, 0.5-5 parts of roasted liquorice, 1-6 parts of dried tangerine peel, 2-10 parts of malt and 0.5-5 parts of perilla seed, calculated on a weight basis.

2. The Chinese medicine composition according to claim 1, characterized in that The invention comprises 3 parts of ginseng, 1 part of dried ginger, 5 parts of Yunfuling, 2 parts of roasted liquorice root, 3 parts of dried tangerine peel, 5 parts of malt and 2 parts of perilla seed, calculated by weight.

3. The Chinese medicine composition according to claim 1 or 2, characterized in that The Chinese medicine composition is in the form of an oral liquid dosage form.

4. The Chinese medicine composition according to any one of claims 1 to 3, characterized in that The traditional Chinese medicine composition further comprises a pharmaceutically or food-acceptable carrier.

5. Use of a Chinese medicine composition in the preparation of a product for preventing, alleviating or improving chronic obstructive pulmonary disease, characterized in that: The Chinese medicine composition is the Chinese medicine composition according to any one of claims 1 to 4.

6. Use of a Chinese medicine composition in the preparation of a product having the function of reducing inflammation levels in the lungs, serum, and colon of humans or animals, characterized in that: The Chinese medicine composition is the Chinese medicine composition according to any one of claims 1 to 4.

7. The use according to claim 6, characterized in that The product having the function of reducing the inflammation level in the lungs, serum and colon of humans or animals can reduce the TNF-α content in the lungs, serum and colon of humans or animals.

8. Use of a Chinese medicine composition in the preparation of a product having the function of repairing the intestinal microenvironment of a human or animal, characterized in that: The Chinese medicine composition is the Chinese medicine composition according to any one of claims 1 to 4.

9. The use according to claim 8, characterized in that The product with the function of repairing the intestinal microenvironment of humans or animals is to repair the intestinal mucosal barrier of humans or animals by increasing the sIgA content in the lungs and colons of humans or animals.

10. A method for preparing a traditional Chinese medicine composition for preventing and treating chronic obstructive pulmonary disease, characterized in that: The following steps are involved: S1: decocting the traditional Chinese medicine composition according to any one of claims 1 to 4 and cooling to room temperature; S2: The medicinal liquid obtained in S1 is concentrated into a thick extract, and placed in a -20°C refrigerator for storage until further use, wherein the extraction method in S1 is any one of water decoction, maceration, percolation, reflux, solvent extraction, steam distillation, supercritical fluid extraction, ultrafine grinding technology, semi-bionic extraction, ultrasonic extraction, cyclone extraction or pressurized countercurrent extraction.

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