Treatment effect of natural product composition on chronic obstructive pulmonary disease

Abstract

The invention belongs to the technical field of medicines, and discloses an application of a natural product composition in medicines related to a COPD (chronic obstructive pulmonary disease) treatment effect. In particular, the disclosed composition is applied to preparation of drugs playing a protective role in preventing and / or treating pulmonary shortness of breath, lung injury, oxidative stress and inflammatory response caused by COPD. Pharmacological experiments prove that the four components of baicalein, arecoline, magnolol and isoquercetin in the composition can jointly exert anti-inflammatory and anti-oxidation effects in the treatment of COPD (chronic obstructive pulmonary disease), and meanwhile, the composition can improve the lung function and promote the repair of lesion lung tissues.

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical technology. Specifically, it relates to the application of a composition in the preparation of a drug for preventing, alleviating, and / or treating chronic obstructive pulmonary disease and its induced immune function damage, spontaneous pneumothorax, obstructive emphysema, and respiratory failure complications. Background Art

[0002] Chronic obstructive pulmonary disease (COPD) is a complex and long-term inflammatory lung disease, which is characterized by a high prevalence rate, high mortality rate, high disability rate, and heavy economic burden, posing a huge challenge and threat to human health. Moreover, its incidence and mortality rates are on the rise year by year. It is predicted that COPD will become the third leading cause of death globally in 2030. The main pathological features of the lungs of COPD patients include chronic airway inflammation, accompanied by infiltration of various inflammatory cells and airway remodeling, including abnormalities of various inflammatory interleukins, tumor necrosis factor-α, etc. The main treatment drugs for stable COPD are long-acting muscarinic antagonists, inhaled glucocorticoids, or long-acting β2 agonists, etc. Although they can relieve the symptoms of patients, their adverse reactions (such as adverse reactions in the cardiac system, osteoporosis, etc.) cannot be ignored, especially in elderly patients. Most COPD patients are not satisfied with the therapeutic effects of these drugs. Therefore, the research on alternative drugs is relatively urgent. Cigarette is the most important inducing factor for COPD. It can cause progressive proteolysis, inflammatory reactions, and lead to vascular reactive responses such as emphysema, small airway obstruction, and pulmonary hypertension. At the same time, respiratory tract infections have been considered as an important factor inducing acute exacerbation of COPD. Therefore, lipopolysaccharide (LPS) is instilled into the trachea to induce acute exacerbation of COPD and construct an acute exacerbation model of COPD.

[0003] Due to the advantages of good effectiveness and low side effects of the active ingredients in Chinese herbal medicines, it has become an increasingly popular treatment method. According to existing reports, baicalein and honokiol have pharmacological effects such as anti-inflammatory, antioxidant, antithrombotic, and tissue protection [1,2] ; arecoline has anticoagulant effects on the one hand and cholinomimetic effects on the other hand, activating cholinergic receptors and exciting the parasympathetic nerve, thereby repairing lesions [3] ; isoquercetin has anti-inflammatory, antioxidant, and neuroprotective effects [4] ; these four compounds can effectively improve the body function, promote the repair of diseased tissues, inhibit thrombus formation, and protect nerves, which match the symptoms caused by COPD.

[0004] In Chinese Patent CN103724328A, Boehringer Ingelheim International GmbH discloses novel antagonists of C-C chemokine receptor 2 and their use as medicaments for treating disorders and diseases, especially lung diseases such as asthma and COPD. [5] . In Chinese Patent CN106660975B, Dongpei Pharmaceutical Co., Ltd. discloses 2-aryl-4-hydroxy-1,3-thiazole derivatives as TRPM8 inhibitors for treating neuralgia, pain, COPD and asthma. [6] . In Chinese Patent CN1195496C, the invention of SmithKline Beecham Corporation relates to controlled or sustained release formulations designed to deliver PDE4 inhibitors for treating inflammatory diseases such as asthma or COPD. [7] . In Chinese Patent CN102858773B, Chiesi Farmaceutici S.p.A. discloses the use of a pyrimidine derivative as a neutrophil elastase inhibitor in respiratory diseases such as COPD. [8] . In Chinese Patent CN1427718A, AstraZeneca Limited discloses the use of myeloperoxidase inhibitors in the treatment of COPD. [9] . In Chinese Patent CN103547261A, the University of Texas System Board of Regents discloses embodiments of methods and compositions involving aldose reductase inhibitors for treating COPD.

[10] . In Chinese Patent CN102985100A, MedImmune Limited and McMaster University disclose methods for treating COPD exacerbations with antibodies and antagonists of IL receptor 1 or IL-1α.

[11] . In Chinese Patent CN104684551A, Cardiff University Consultants Limited and The Royal College of London disclose the use of calcium / cation-sensing receptor antagonists such as NPS89636 in the treatment of inflammatory lung diseases (asthma or COPD).

[12] . In Chinese Patent CN114786775A, Sanofi Biotech and Regeneron Pharmaceuticals propose a method for treating COPD by administering an IL-33 antagonist.

[13] . The above patents relate to antagonists or inhibitors currently used in the treatment of COPD, which are essentially different from the compounds described in the present invention.

[0005] In Chinese Patent CN113816934B, the Institute of Zoology, Guangdong Academy of Sciences discloses a method for synthesizing disubstituted chromanones and their application in treating pulmonary inflammations such as COPD.

[14] . In Chinese Patent CN1984658B, Celtic Europe Limited discloses opioids for treating COPD.

[15] 。In Chinese Patent CN102405219A, AstraZeneca (Sweden) Limited announced the tosylate of 5-pyrazolyl-2-pyridone derivatives for the treatment of COPD

[16] 。In Chinese Patent CN103889970B, the invention of Boehringer Ingelheim International GmbH relates to piperidino-dihydrothiophenopyrimidine sulfoxide and its use in the treatment of COPD and asthma

[17] 。In Chinese Patent CN113773295B, the Guangdong Academy of Sciences Institute of Zoology disclosed a method for synthesizing mono-substituted dihydrochromone and its application in the treatment of pulmonary inflammation such as COPD

[18] 。In Chinese Patents CN100584324C and CN1923187A, Novartis International Pharmaceutical Ltd. announced the use of camostat and secretin receptor ligands in the preparation and treatment of cystic fibrosis and COPD [19,20] 。In Chinese Patent CN101351448A, AstraZeneca (Sweden) Limited announced a new 1-benzyl-4-piperidineamine for the treatment of COPD and asthma

[21] 。In Chinese Patent CN102481282A, the National University of Singapore disclosed the use of artemisinin derivatives for the treatment of asthma and COPD

[22] 。In Chinese Patent CN107998147A, the First Affiliated Hospital of Guangzhou Medical University disclosed an aerosol inhalation preparation for inhibiting or treating COPD, and the aerosol inhalation preparation is a NaHS aerosol inhalation agent

[23] 。In Chinese CN113975266A, the Fifth Affiliated Hospital of Guangzhou Medical University disclosed the application of formononetin in the treatment of COPD

[24] 。The above patents involve monomer components currently used in the treatment of COPD, which are essentially different from the compounds described in the present invention.

[0006] In Chinese Patent CN104055765B, Chiesi Farmaceutici S.p.A. disclosed the combination therapy of glycopyrronium bromide and formoterol for COPD

[25] 。In Chinese Patent CN111615385B, Emphysema Solutions Pte. Ltd. disclosed compositions and methods for the treatment of emphysema and other forms of COPD, comprising an active agent containing a copper compound, preferably copper sulfate, and a glycosaminoglycan, preferably heparin, or a physiologically acceptable salt thereof

[26] 。In Chinese Patent CN110152003B, the First Affiliated Hospital of Wenzhou Medical University disclosed a compound drug for the treatment of COPD and its preparation method, including a combination of palmatine or a pharmaceutically acceptable salt thereof, a β2 receptor agonist, and a pharmaceutically acceptable carrier

[27] 。In Chinese Patent CN1913883A, MEDA Pharma GmbH & Co. KG proposed a combination of an anticholinergic and a glucocorticoid for the long-term treatment of asthma and COPD

[28] 。In Chinese Patent CN104321066A, Sanofi disclosed a composition containing polar glycolipids for the treatment and / or prevention of pain and / or COPD

[29] 。In Chinese Patent CN1682724A, Yang Ruochuan and Gao Shi proposed an oral therapeutic agent for the treatment of COPD containing ipratropium bromide and salbutamol

[30] 。In Chinese Patent CN101296698A, AstraZeneca (Sweden) AB disclosed a pharmaceutical composition, including the use of a β2 agonist and various compounds in the treatment of respiratory diseases, especially COPD and asthma

[31] 。In Chinese Patent CN102985098A, Biolika S.p.A. disclosed an extract made from Thymus L. combined with Primula veris or Hedera helix for the prevention and treatment of COPD, and also disclosed the corresponding drug and its application

[32] 。In Chinese Patent CN106470700A, Teva Pharmaceutical Industries Ltd. provided a combination product, which includes a combination of an inhalable long-acting muscarinic antagonist composition for the long-term treatment of COPD and an inhalable fixed-dose composition containing budesonide and formoterol or a pharmaceutically acceptable salt thereof

[33] 。In Chinese Patent CN1674939A, Viatris GmbH & Co. KG disclosed a new combination of a glucocorticoid and a phosphodiesterase-4 inhibitor for the treatment of respiratory diseases, allergic diseases, asthma and COPD

[34] 。In Chinese Patent CN106488770A, Teva Pharmaceutical Industries Ltd. provided a composition containing formoterol or a pharmaceutically acceptable salt thereof and budesonide in a fixed dose, which is used for the long-term treatment of COPD and the treatment of acute exacerbations of COPD

[35] 。In Chinese Patent CN112603983A, Wuhan KingMed Diagnostics Co., Ltd. disclosed a pharmaceutical composition for the treatment of COPD with pulmonary fibrosis

[36] 。In Chinese Patent CN106659750A, Korea Research Institute of Bioscience and Biotechnology disclosed a pharmaceutical composition containing Pistacia weinmannifolia extract, its fractions or compounds isolated therefrom for the prevention or treatment of COPD

[37] 。In Chinese Patent CN107427500A, Georgia State University Research Foundation Inc. proposed a composition and method for the treatment of COPD and other inflammatory conditions including at least two active agents

[38] In Chinese Patent CN104758294A, Guangzhou Institute of Respiratory Diseases, Sun Yat-sen University, and The First Affiliated Hospital of Guangzhou Medical University disclosed an inhaled pharmaceutical composition for the treatment of COPD and asthma and its preparation method.

[39] The above patent relates to pharmaceutical compositions currently used in the treatment of COPD, which are essentially different from the combination of the natural compounds described in the present invention.

[0007] Currently, the compositions for the treatment of COPD include Western medicine combinations composed of glycopyrronium bromide, formoterol, etc., traditional Chinese medicine combinations composed of red ginseng, ephedra, white mustard seed, etc., and biopharmaceuticals such as amino acids or antibodies, etc. However, the therapeutic effect of combinations of natural products on COPD has not been seen. The present invention discovers that the combination of these four natural products can exert a therapeutic effect on COPD. Among them, the composition is selected through network pharmacology target action calculation, combined with in vitro bioactivity testing and the influence of factors related to lung injury, and comprehensively considering the treatment characteristics of the disease. In terms of the mechanism of action, natural products with antiviral, anti-inflammatory, nerve repair-promoting, and parasympathetic nerve-regulating effects are selected for combination, which can effectively improve the symptoms of pneumonia and prolong the action time of the drug, and the substance composition has good physical and chemical properties and compatibility of crystal forms. To sum up, there has been no research report on the combination of these four natural compounds and the therapeutic effect of this combination on COPD. In view of this, the present invention is specifically proposed. Summary of the Invention

[0008] The technical problem to be solved by the present invention is to invent a brand-new natural product composition and apply it to the prevention, alleviation, and / or treatment of COPD and its complications of immune function damage, spontaneous pneumothorax, obstructive emphysema, and respiratory failure.

[0009] The present invention realizes the invention purpose through the following technical solutions:

[0010] One of the purposes of the present invention: To provide a natural product composition, which is obtained by combining the raw materials according to the described parts by weight.

[0011] Another purpose of the present invention: To provide the application of the natural product composition in related drugs and other products for the treatment of COPD.

[0012] Another purpose of the present invention: To provide the application of the natural product composition in the prevention and / or treatment of inflammatory reactions, oxidative stress, lung function decline, lung tissue lesions, etc. caused by COPD.

[0013] Another purpose of the present invention: The natural product composition of the present invention can improve the abnormally accelerated respiratory rate, improve respiratory function, and achieve the therapeutic effect on COPD.

[0014] Fifth object of the present invention: The natural product composition of the present invention can achieve the therapeutic effect on COPD by restoring the alveolar state of damaged lung tissue, reducing the pulmonary edema state caused by COPD, and promoting the repair of diseased lung tissue.

[0015] Sixth object of the present invention: The natural product composition of the present invention reduces the SOD level in serum and increases the GSH level to achieve antioxidant effects and reach the therapeutic purpose of COPD.

[0016] Seventh object of the present invention: The natural product composition of the present invention can achieve anti-inflammatory effects and reach the therapeutic purpose of COPD by reducing the number of white blood cells in broncho-alveolar lavage fluid (BALF) and reducing the levels of IL-8, IL-1β, TNF-α, and IFN-γ factors in serum.

[0017] To solve the technical problems of the present invention, the following technical solutions are provided:

[0018] The technical solution of the present invention provides a natural product composition, which is composed of the compounds baicalein, arecoline, magnolol, and isoquercitrin.

[0019]

[0020]

[0021] Each 100 parts by weight of the formula is made of the following raw materials in parts by weight: 20-60 parts by weight of baicalein, 10-40 parts by weight of arecoline, 1-20 parts by weight of magnolol, and 20-60 parts by weight of isoquercitrin.

[0022] Further preferably: Each 100 parts by weight of the natural product composition is made of the following raw materials in parts by weight: 40 parts by weight of baicalein, 20 parts by weight of arecoline, 8 parts by weight of magnolol, and 32 parts by weight of isoquercitrin.

[0023] Further preferably, a natural product composition is provided, and the pharmaceutical composition contains the formula of baicalein, arecoline, magnolol, and isoquercitrin as described in the first aspect of the technical solution or a pharmaceutically acceptable carrier or excipient.

[0024] The pharmaceutical composition of the natural product composition of the present invention can be prepared according to methods well known in the art. For this purpose, if necessary, the compounds of the present invention can be combined with one or more solid or liquid pharmaceutical excipients and / or adjuvants to form a suitable administration form or dosage form for use as a human or veterinary medicine.

[0025] The natural product composition of the present invention or the pharmaceutical composition containing the same can be administered in unit dosage form, and the administration route can be enteral or parenteral, such as oral, intramuscular, subcutaneous, nasal, oral mucosa, skin, peritoneal or rectal, etc.

[0026] The administration route of the natural product composition of the present invention or the pharmaceutical composition containing the same can be injection. Injection includes intravenous injection, intramuscular injection, subcutaneous injection, intradermal injection and acupoint injection, etc.

[0027] The dosage form can be liquid dosage form or solid dosage form. For example, the liquid dosage form can be true solution type, colloid type, particulate dosage form, emulsion dosage form, suspension dosage form. Other dosage forms such as tablets, capsules, dripping pills, aerosols, pills, powders, solution, suspension, emulsion, granules, suppositories, freeze-dried powder injections, etc.

[0028] The natural product composition of the present invention can be made into conventional preparations, or sustained-release preparations, controlled-release preparations, targeted preparations and various particulate drug delivery systems.

[0029] The technical solution of the present invention provides the application of the natural product composition described in the first aspect and the pharmaceutical composition containing a natural product composition described in the second aspect in the preparation of drugs for preventing, alleviating and / or treating COPD. The COPD and its complications include immune function impairment, spontaneous pneumothorax, obstructive pulmonary emphysema, respiratory failure.

[0030] The present invention can be achieved by the following technical solutions. By using male Balb / c mice, a COPD model is established by the method of inhaling cigarette smoke and injecting LPS into the trachea. During the administration process, the body weight and death of the animals are recorded. One day before the end of the experiment, the respiratory frequency of each group of mice is measured; two weeks after drug treatment, blood is collected to measure the levels of oxidative factors and anti-inflammatory factors in the serum; the alveolar lavage fluid is collected to measure the number of white blood cells, and a part of the left lung tissue is taken for fixation and section staining to observe the pathological state, so as to judge the therapeutic effect of the natural product composition on COPD. The present invention achieves the invention purpose through the following technical solutions:

[0031] Beneficial technical effects: The composition formed by the natural products of the present invention has prominent pharmacological activities, can play a synergistic role, effectively improve lung function, relieve the state of pulmonary edema, repair damaged alveoli and lung tissues, reduce the level of SOD, increase the level of GSH to achieve antioxidant effects, reduce the number of white blood cells in bronchoalveolar lavage fluid and the levels of inflammatory factors such as IL-8, IL-1β, IFN-γ, and TNF-α in serum, achieve anti-inflammatory effects to relieve COPD symptoms, and achieve the treatment purpose of COPD and its complications. The composition has high safety, reliable ingredient sources, and low production costs, and has good market development prospects. It is applicable to the preparation of drugs for preventing, relieving, and / or treating COPD diseases and their induced immune function damage, spontaneous pneumothorax, obstructive pulmonary emphysema, and respiratory failure complications. Description of the Drawings

[0032] Figure 1 Effect of the natural product composition on the respiratory rate of COPD mice induced by combined stimulation of cigarette smoke and LPS;

[0033] Figure 2 Effect of the natural product composition on the wet / dry ratio of the lungs of COPD mice induced by combined stimulation of cigarette smoke and LPS;

[0034] Figure 3 Effect of the natural product composition on the damaged lung tissues of COPD mice induced by combined stimulation of cigarette smoke and LPS; Figure 4 Effect of the natural product composition on the oxidative stress factors SOD and GSH in COPD mice induced by combined stimulation of cigarette smoke and LPS;

[0035] Figure 5 Effect of the natural product composition on the number of white blood cells in BALF of COPD mice induced by combined stimulation of cigarette smoke and LPS;

[0036] Figure 6 Effect of the natural product composition on the serum inflammatory cytokines IL-8, TNF-α, IL-1β, and IFN-γ in COPD mice induced by combined stimulation of cigarette smoke and LPS; Detailed Embodiments

[0037] To make the objectives, technical solutions, and advantages of the present invention clearer, the present invention will be further described in detail below with reference to the drawings.

[0038] Table 1 Abbreviation Explanation

[0039]

[0040] Example 1

[0041] Effect of Natural Product Composition on Respiratory Rate of COPD Mice Induced by Combined Stimulation of Cigarette Smoke and LPS 1. Experimental Method

[0042] In the example, 28 male SPF-grade Balb / c mice weighing 18 - 20 g were selected and randomly divided into 4 groups of 7 mice each. The above 4 groups were set as normal control group, model group, low-dose and high-dose composition groups (100 mg / kg, 300 mg / kg) respectively. The corresponding dose of drug was given by gavage for 14 consecutive days. On the last day of drug administration, the respiratory frequency of each group of mice was measured using the BL-420s biological function experimental system, and the controlled parameters were 50 mV and 20 Hz respectively. The mice were anesthetized with oxygen and isoflurane (1 - 2%).

[0043] 2. Experimental Results

[0044] After 1 month of combined stimulation with cigarette smoke and LPS, shortness of breath occurred. The respiratory rate of the model group was significantly faster than that of the normal group (P < 0.001), while the administration of the composition at doses of 100 and 300 mg / kg significantly reduced the respiratory rate and restored it to the normal respiratory rate range (P < 0.001)( Figure 1 , Table 2).

[0045] Table 2 Effect of Natural Product Composition on Respiratory Frequency of COPD Mice (Mean ± SD, n = 6)

[0046]

[0047] Example 2

[0048] Effect of Natural Product Composition on Lung Tissue of COPD Mice Induced by Combined Stimulation of Cigarette Smoke and LPS 1. Experimental Method

[0049] In the example, 28 male SPF-grade Balb / c mice weighing 18 - 20 g were selected and randomly divided into 4 groups of 7 mice each. The above 4 groups were set as normal control group, model group, low-dose and high-dose composition groups (100 mg / kg, 300 mg / kg) respectively. The corresponding dose of drug was given by gavage for 14 consecutive days. For each group of mice, a part of the left lung was dissected, rinsed with physiological saline to remove excess blood, and then the excess moisture was blotted with filter paper and weighed, recorded as wet weight. After marking, the dried lung tissue was placed in an 80°C oven for 48 h and weighed again, recorded as dry weight. The wet-dry mass ratio was calculated to reflect the degree of lung tissue injury of the mice.

[0050] Another part of the left lung of each group of mice was dissected, fixed in tissue fixative, dehydrated, paraffin-embedded and sectioned, and stained with hematoxylin-eosin.

[0051] 2. Experimental Results

[0052] The wet / dry ratio can be used to evaluate the severity of pulmonary edema. Compared with the control group, the wet / dry ratio of the lungs of mice in the model group was significantly increased (P < 0.01), indicating that lung injury led to an increase in lung water content. Compared with the model group, the wet / dry ratio of the lungs of mice in the administration group was significantly decreased (P < 0.05, P < 0.01)( Figure 2 ).

[0053] By comparing the lung tissue sections after staining, compared with the control group, the alveolar structure in the model group was disordered, the alveolar wall was thinned, the alveolar septum was ruptured, the alveoli were dilated, and the number of alveoli was significantly reduced. However, the above pathological changes in the lung tissue of mice in the composition group were all improved( Figure 3 , Table 3).

[0054] Table 3 Effects of natural product composition on the wet / dry ratio of the lungs of COPD mice (Mean±SD, n = 3)

[0055]

[0056] Mean±SD, n = 3; ## P < 0.01 vs normal group, * P < 0.05, ** P < 0.01 vs model group

[0057] Example 3

[0058] Effects of natural product composition on oxidative stress factors in COPD mice induced by combined stimulation of cigarette smoke and LPS

[0059] 1. Experimental method

[0060] In Example 28 male SPF-grade Balb / c mice weighing 18 - 20 g were selected and randomly divided into 4 groups with 7 mice in each group. The above 4 groups were respectively set as the normal control group, the model group, and the low and high dose groups of the composition (100 mg / kg, 300 mg / kg). The corresponding doses of drugs were administered by gavage for 14 consecutive days, and then blood was collected. The blood was placed in 1.5 mL EP tubes, left at room temperature for 2 h, and then placed in a 4°C pre-cooled low-temperature centrifuge and centrifuged at 3000 rpm for 15 min. The serum was aliquoted into EP tubes and stored at -80°C for later measurement. The SOD activity was detected by the WST-1 method, and the GSH activity was detected by the microplate method.

[0061] 2. Experimental results

[0062] Compared with the control group, the SOD level in the model group was increased (P < 0.001), and the GSH level was decreased (P < 0.001). Compared with the model group, the compositions at 100 and 300 mg / kg could significantly reduce the SOD level (P < 0.001) and significantly reverse the GSH level (P < 0.01, P < 0.001)(Figure 4 , Table 4).

[0063] Effect of natural product composition on the wet / dry ratio of lungs in COPD mice (Mean±SD, n = 6)

[0064]

[0065] Mean±SD, n = 6; ### P < 0.001 vs normal group, ** P < 0.01, *** P < 0.001 vs model group

[0066] Example 4

[0067] Effect of natural product composition on serum inflammatory factors in COPD mice induced by combined stimulation of cigarette smoke and LPS

[0068] 1. Experimental method

[0069] For this example, 28 male SPF-grade Balb / c mice weighing 18 - 20 g were selected and randomly divided into 4 groups of 7 mice each. The above 4 groups were respectively set as normal control group, model group, low-dose and high-dose groups of the composition (100 mg / kg, 300 mg / kg). The corresponding doses of drugs were administered by gavage for 14 consecutive days, and then blood was collected. The blood was placed in 1.5 mL EP tubes, left at room temperature for 2 h, and then put into a pre-cooled 4℃ low-temperature centrifuge and centrifuged at 3000 rpm for 15 min. The serum was aliquoted into EP tubes and stored at -80℃ for further testing.

[0070] After blood collection, 4 mice from each group were taken, fixed on the surgical board, the neck skin was incised, and the trachea was separated and exposed. A transverse incision was made under the trachea, and an 8-gauge gavage needle was inserted through the incision and fixed with a ligature. 0.3 mL of pre-cooled normal saline was slowly injected, and intermittent aspiration was performed for 10 seconds. BALF was recovered three times in sterile centrifuge tubes, put into a pre-cooled 4℃ low-temperature centrifuge, centrifuged at 3000 rpm for 15 min, the supernatant was transferred into an EP tube, and stored at -80℃ for further testing. The centrifuged BALF precipitate was resuspended with 200 μL of normal saline, 20 μL was added to the cell counting chamber, and white blood cells were counted under a microscope. Another 20 μL was placed on a glass slide, air-dried, and the BALF precipitate was stained with Wright Giemsa staining solution and observed under an inverted microscope.

[0071] 2. Experimental results

[0072] The number of white blood cells in the BALF of the model group mice was significantly higher than that of the normal group (P < 0.001). The compositions at 100 and 300 mg / kg significantly reduced the number of white blood cells (P < 0.001). Using the Wright-Giemsa staining method, after staining and observing under an inverted microscope, the number of stained cells in the visual field of the mice in the administration group was significantly reduced compared with that of the model group( Figure 5 , Table 5).

[0073] Table 5 Effects of natural product composition on the number of white blood cells in BALF of COPD mice (Mean±SD)

[0074]

[0075] Mean±SD, n = 4; ### P < 0.001 vs normal group, *** P < 0.001 vs model group

[0076] Compared with the normal group, the levels of serum IL-8, TNF-α, IL-1β, and IFN-γ in the model group mice were significantly increased (P < 0.001). Compared with the model group, the levels of IL-8, TNF-α, IL-1β, and IFN-γ in the administration group mice were significantly decreased (P < 0.001)( Figure 6 , Table 6).

[0077] Table 6 Effects of natural product composition on serum inflammatory factors of COPD mice (Mean±SD, n = 6)

[0078]

[0079] Mean±SD, n = 6; # P < 0.05, ### P < 0.001 vs normal group, * P < 0.05, *** P < 0.001 vs model group References

[0080] [1] Liu XL, Li CY, Chen QJ, et al. Research progress on the main active components and pharmacological effects of Scutellaria baicalensis Georgi[J]. Journal of Xinxiang Medical University, 2023, 40(10): 979-985+990.

[0081] [2] Jia Y, Ren CX, Xia YN, et al. Research status of the pharmacological effects of honokiol[J]. Biotechnology & Chemical Engineering, 2023, 9(03): 170-174.

[0082] [3] Hu JY, Chen X, Ma T, et al. The alleviating and repairing effects and mechanisms of arecoline on nerve injury[J]. Chinese Journal of Pharmacology and Toxicology, 2023, 37(07): 497.

[0083] [4] Nieman DC, Henson DA, Maxwell KR, Williams AS, McAnulty SR, Jin F, Shanely RA, Lines TC. Effects of quercetin and EGCG on mitochondrial biogenesis and immunity. Med Sci Sports Exerc. 2009, 41(7): 1467 - 75.

[0084] [5] Chinese Patent CN103724328A

[0085] [6] Chinese Patent CN106660975B

[0086] [7] Chinese Patent CN1195496C

[0087] [8] Chinese Patent CN102858773B

[0088] [9] Chinese Patent CN1427718A

[0089]

[10] Chinese Patent CN103547261A

[0090]

[11] Chinese Patent CN102985100A

[0091]

[12] Chinese Patent CN104684551A

[0092]

[13] Chinese Patent CN114786775A

[0093]

[14] Chinese Patent CN113816934B

[0094]

[15] Chinese Patent CN1984658B

[0095]

[16] Chinese Patent CN102405219A

[0096]

[17] Chinese Patent CN103889970B

[0097]

[18] Chinese Patent CN113773295B

[0098]

[19] Chinese Patent CN100584324C

[0099]

[20] Chinese Patent CN1923187A

[0100]

[21] Chinese Patent CN101351448A

[0101]

[22] Chinese Patent CN102481282A

[0102]

[23] Chinese Patent CN107998147A

[0103]

[24] Chinese Patent CN113975266A

[0104]

[25] Chinese Patent CN104055765B

[0105]

[26] Chinese Patent CN111615385B

[0106]

[27] Chinese Patent CN110152003B

[0107]

[28] Chinese Patent CN1913883A

[0108]

[29] Chinese Patent CN104321066A

[0109]

[30] Chinese Patent CN1682724A

[0110]

[31] Chinese Patent CN101296698A

[0111]

[32] Chinese Patent CN102985098A

[0112]

[33] Chinese Patent CN106470700A

[0113]

[34] Chinese Patent CN1674939A

[0114]

[35] Chinese Patent CN106488770A

[0115]

[36] Chinese Patent CN112603983A

[0116]

[37] Chinese Patent CN106659750A

[0117]

[38] Chinese Patent CN107427500A

[0118]

[39] Chinese Patent CN104758294A.

Claims

1. A natural product composition, which is composed of the compounds baicalein, arecoline, magnolol and isoquercitrin.

2. The composition according to claim 1, characterized in that, Each 100 parts by weight of the formula is made from the following raw materials in parts by weight: 20 - 60 parts by weight of baicalein, 10 - 40 parts by weight of arecoline, 1 - 20 parts by weight of magnolol, 20 - 60 parts by weight of isoquercitrin. The chemical structure in this composition is as shown in Claim 1.

3. Use of the natural product composition according to any one of Claims 1 to 2 in the preparation of a drug for preventing, alleviating and / or treating COPD and immune function damage, spontaneous pneumothorax, obstructive emphysema, respiratory failure complications caused thereby.

4. The application according to claim 3, wherein This natural product composition can achieve the therapeutic effect on COPD and its complications by improving lung function.

5. The application according to claim 4, wherein This natural product composition effectively improves the phenomenon of increased respiratory rate caused by COPD and improves lung function.

6. The application according to claim 3, characterized in that, This natural product composition can achieve the therapeutic effect on COPD and its complications by promoting the repair of diseased lung tissue.

7. The application according to claim 6, wherein This natural product composition restores the alveolar state of damaged lung tissue, reduces the pulmonary edema state caused by COPD, and promotes the repair of diseased lung tissue.

8. The application according to claim 3, wherein This natural product composition achieves the therapeutic effect on COPD and its complications through antioxidant effects.

9. The application according to claim 8, wherein This natural product composition achieves antioxidant effects by reducing the level of superoxide dismutase (SOD) in serum and increasing the level of glutathione (GSH).

10. The application according to claim 3, wherein This natural product composition achieves the therapeutic effect on COPD and immune function damage, spontaneous pneumothorax, obstructive emphysema, respiratory failure complications caused thereby through anti-inflammatory effects.

11. The application according to claim 10, characterized in that, This natural product composition achieves anti-inflammatory effects by reducing the number of white blood cells in lung tissue and reducing the levels of interleukin-8 (IL-8), interleukin-1β (IL-1β), interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) in serum.

12. The application according to any one of claims 1 to 11, characterized in that, The single-dose application dose of this natural product composition for preventing and / or treating body damage in adults is 10 - 1000 mg / kg, preferably 10 - 500 mg / kg.

13. The application according to claim 12, wherein The drug for preventing and / or treating the therapeutic effect of COPD includes a preparation made from a natural product composition and a pharmaceutically acceptable carrier or excipient, and the preparation dosage form is selected from: oral preparation, injection dosage form or dosage form for administration through skin and mucosa.

14. The application according to claim 13, characterized in that, The oral preparation includes tablets, sustained-release agents, capsules, controlled-release agents, enteric-coated agents, dripping pills or liquid preparations, and the injection dosage forms include intramuscular injection, intravenous injection or intravenous drip.

Images