Use of the composition in the preparation of a medicament for preventing or treating lung injury

Abstract

The present invention provides the use of a composition in the preparation of a medicament for preventing or treating lung injury, and the composition comprises: immature tangerine peel, bitter orange, perilla stem, magnolia bark, poria cocos, prepared pinellia rhizome, bile-processed arisaema tuber, cicada slough, semen oroxylae, ginger and medicated leaven. The composition of the present invention can effectively prevent or treat lung injury diseases, laying a foundation for the scientific research and clinical application of lung injury diseases, and having good application prospects.

Description

Technical Field

[0001] The present invention relates to the field of medicine. Specifically, the present invention relates to the use of a composition in the preparation of a drug for preventing or treating lung injury diseases. Background Art

[0002] Lung function injury refers to the phenomenon of mixed ventilation disorder in the lungs, and this disease causes great damage to the patient's body. Lung function impairment will cause the patient to have symptoms such as coughing and excessive phlegm. As the condition worsens, the patient will experience symptoms such as shortness of breath, physical exhaustion, and poor physical condition. Lung function injury is generally caused by various diseases, mainly including bronchitis, emphysema, lung abscess, or pulmonary embolism, etc., and may also be pneumonia, tuberculosis, pneumothorax, pulmonary bulla, lung tumor, etc. The lesion generally occurs in the trachea, bronchial mucosa, and surrounding tissues.

[0003] PM2.5, also known as fine particulate matter, refers to particulate matter with an aerodynamic equivalent diameter less than or equal to 2.5 micrometers in ambient air. After entering the body, PM2.5 stimulates inflammatory cells to release a large number of inflammatory factors through various pathways, inducing a severe inflammatory response. The destructive effect of excessive inflammatory factors on the body will damage the normal tissues or cells of the respiratory tract, destroy the alveolar cavity vascular basement membrane and capillary membrane structure, increase the cell membrane permeability, and cause the leakage of various protease and other contents inside the cell.

[0004] At present, the treatment of this disease mainly relies on drug treatment. Common drugs include antibiotic drugs such as penicillin, amoxicillin, cephalosporins, etc., and their treatment purpose is anti-infection treatment to prevent the further development of the disease; cough drugs, whose treatment purpose is to relieve the patient's cough symptoms; and some expectorant drugs, etc. However, these drugs cannot fundamentally treat the disease and will also have some side effects. The greatest advantage of traditional Chinese medicine treatment is to prevent disease before it occurs and prevent the progression of the disease once it has occurred. In the prevention and treatment of lung injury, traditional Chinese medicine adopts the treatment principle of strengthening healthy qi and eliminating pathogenic factors. One is to assist healthy qi and enhance the body's immunity, and the other is to eliminate pathogenic factors, resist external pathogens, expel pathogenic factors, improve the body's immunity and adaptability, and prevent the occurrence and further aggravation of the disease. Chinese patent medicines can improve the lung function of patients with lung injury, reduce the release of inflammatory factors in the body, and overall improve the body's immunity and lung function. At present, there is no effective Chinese patent medicine for preventing and treating high airway injury caused by PM2.5. Therefore, drugs for preventing or treating lung injury, especially lung injury caused by PM2.5, still need to be studied. Summary of the Invention

[0005] The present invention aims to solve at least one of the technical problems existing in the prior art to at least a certain extent. For this purpose, the present invention proposes the use of a composition in the preparation of a drug. By using this composition, lung injury diseases can be effectively prevented or treated, laying a foundation for related scientific research and clinical applications, and having good application prospects.

[0006] The present invention provides the use of a composition in the preparation of a drug. According to an embodiment of the present invention, the drug is used for preventing or treating lung injury, and the composition includes: immature tangerine peel, bitter orange, perilla stem, magnolia bark, poria cocos, prepared pinellia rhizome, arisaema cum bile, cicada slough, semen oroxylae, ginger, and medicated leaven.

[0007] Immature tangerine peel and bitter orange soothe the liver and regulate qi, smooth the qi movement, and when the qi is smooth, phlegm will disappear, serving as the monarch drugs. Perilla stem and magnolia bark strengthen the effects of soothing the liver and relieving depression, regulating qi and resolving phlegm; Poria cocos, prepared pinellia rhizome, and arisaema cum bile strengthen the spleen and harmonize the stomach, dry dampness and resolve phlegm to eliminate the source of phlegm production, and altogether serve as the ministerial drugs. Cicada slough and semen oroxylae disperse wind, clear heat, and ventilate the lung, moisten dryness and benefit the throat to improve voice, to relieve symptoms such as dry mouth, throat dryness, and hoarseness. Ginger and medicated leaven harmonize the middle and promote digestion, and altogether serve as the assistant and guiding drugs. The combined action of these several herbs can effectively achieve the effect of preventing or treating lung injury.

[0008] According to an embodiment of the present invention, the use of the above composition in the preparation of a drug may further have the following additional technical features:

[0009] According to an embodiment of the present invention, the composition includes: 40 - 60 parts of immature tangerine peel, 40 - 60 parts of bitter orange, 40 - 60 parts of perilla stem, 40 - 60 parts of magnolia bark, 40 - 60 parts of poria cocos, 40 - 60 parts of prepared pinellia rhizome, 40 - 60 parts of arisaema cum bile, 40 - 60 parts of cicada slough, 40 - 60 parts of semen oroxylae, 6 - 8 parts of ginger, and 40 - 60 parts of medicated leaven. The several herbs are compounded in the above proportions, having good medicinal effects and can effectively achieve the effect of preventing or treating lung injury.

[0010] According to an embodiment of the present invention, the composition includes: poria cocos, prepared pinellia rhizome, bitter orange, immature tangerine peel, arisaema cum bile, tangerine peel, amomum villosum, amomum kravanh, areca nut, albizia bark, medicated leaven, perilla stem, ginger, cicada slough, semen oroxylae, and magnolia bark.

[0011] Immature tangerine peel and bitter orange soothe the liver and regulate qi, smooth the qi movement, and when the qi is smooth, phlegm will disappear, serving as the monarch drugs. The combination of areca nut, perilla stem, magnolia bark, and albizia bark strengthens the effects of soothing the liver and relieving depression, regulating qi and resolving phlegm; Poria cocos, amomum villosum, prepared pinellia rhizome, tangerine peel, amomum kravanh, and arisaema cum bile strengthen the spleen and harmonize the stomach, dry dampness and resolve phlegm to eliminate the source of phlegm production, and altogether serve as the ministerial drugs. Cicada slough and semen oroxylae disperse wind, clear heat, and ventilate the lung, moisten dryness and benefit the throat to improve voice, to relieve symptoms such as dry mouth, throat dryness, and hoarseness. Ginger and medicated leaven harmonize the middle and promote digestion, and altogether serve as the assistant and guiding drugs. The combined use of all herbs achieves the effects of soothing the liver and regulating qi, resolving phlegm and relieving sore throat. The combined action of these several herbs can effectively achieve the effect of preventing or treating lung injury.

[0012] According to an embodiment of the present invention, the composition comprises: 40-60 parts of Poria cocos, 40-60 parts of Pinellia ternata processed with Rhizoma Zingiberis Recens, 40-60 parts of Fructus Aurantii Immaturus, 40-60 parts of Pericarpium Citri Reticulatae Viride, 40-60 parts of Arisaema cum Bile, 40-60 parts of Exocarpium Citri Grandis, 40-60 parts of Fructus Amomi, 15-35 parts of Semen Amomi Rotundus, 40-60 parts of Semen Arecae, 40-60 parts of Cortex Albiziae, 40-60 parts of Massa Medicata Fermentata, 40-60 parts of Caulis Perillae, 6-8 parts of Rhizoma Zingiberis Recens, 40-60 parts of Cicada Slough, 40-60 parts of Semen Oroxyli, and 40-60 parts of Magnolia officinalis. When several herbs are compounded in the above proportions, they have good medicinal effects and can effectively prevent or treat lung injury.

[0013] According to an embodiment of the present invention, the lung injury is caused by inhaling PM2.5.

[0014] According to an embodiment of the present invention, the composition is used to alleviate damaged lung tissue structure, alveolar collapse, alveolar septum rupture, and / or inflammatory cell infiltration.

[0015] According to an embodiment of the present invention, the composition is used to reduce the activities of serum acid phosphatase, alkaline phosphatase, and lactate dehydrogenase in lung tissue cells.

[0016] Acid phosphatase (ACP) is a lysosomal enzyme mainly present in macrophages and can participate in the body's defense response. When macrophages phagocytize foreign substances and lyse and die, a large amount of ACP is released from macrophages into the bronchoalveolar lavage fluid. Alkaline phosphatase (AKP) is mainly produced by type II alveolar cells, and the amount of its content indicates the degree of damage to type II alveolar cells. Lactate dehydrogenase (LDH) is a cytoplasmic enzyme widely present in various tissue cells of the body. The LDH in the alveolar cavity mainly comes from leakage of alveolar cells and blood leakage after alveolar cell damage. The LDH level in the alveolar cavity can reflect the degree of damage to the lung tissue cell membrane and is an index reflecting cytotoxicity. The inventors found that the composition of the present invention can effectively reduce the activities of ACP, AKP, and LDH, and is particularly suitable for preventing or treating diseases caused by high airway injury induced by inhaling PM2.5.

[0017] According to an embodiment of the present invention, the composition is used to reduce the expression level of IL-17mRNA in lung tissue, reduce the ratio of the expression levels of Th17mRNA and Treg mRNA, and / or increase the expression level of Foxp3 mRNA.

[0018] Both Th17 and Treg are derived from CD +Derived from CD4+ T lymphocytes, Th17 cells can release interleukin (IL)-17, which has strong pro-inflammatory ability in vivo and can promote T cell proliferation and the expression of various inflammatory mediators. Treg cells mainly play an immunosuppressive role by secreting anti-inflammatory cytokines and can antagonize Th17 cells. Under normal conditions of the body, the dynamic balance between Th17 and Treg regulates autoimmunity in the body, while the imbalance of Th17 / Treg has been found in the occurrence and development of inflammatory diseases of the respiratory system such as high airway inflammation. Studies have found that inhalable particulate matter in the atmosphere, including PM2.5, can bind to the aryl hydrocarbon receptor (AHR), cause oxidative stress and induce bronchus-associated lymphoid tissue to regulate the ratio of Th17 and Treg cells, increase the production of pro-inflammatory cytokines, and lead to lung inflammation and injury.

[0019] Forkhead box P3 (Foxp3) is a conventional marker for identifying Treg cells and a key factor for the differentiation and functional expression of Treg cells. It can reduce inflammatory infiltration, promote virus clearance, avoid excessive non-specific immune responses, and inhibit Th2 responses by secreting anti-inflammatory factors such as TGF-β, playing a protective role in resisting extracellular pathogen invasion and inhibiting autoimmunity.

[0020] The inventors found that the composition of the present invention can reduce the expression level of IL-17 mRNA in lung tissue, reduce the ratio of the expression levels of Th17 mRNA and Treg mRNA, and / or increase the expression level of Foxp3 mRNA, and is particularly suitable for preventing or treating diseases caused by high airway injury induced by inhaled PM2.5.

[0021] According to the embodiments of the present invention, the dosage form of the drug is pills, tablets or capsules.

[0022] The additional aspects and advantages of the present invention will be partly given in the following description, partly will become obvious from the following description, or will be understood through the practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] The above and / or additional aspects and advantages of the present invention will become obvious and easy to understand from the description of the embodiments in conjunction with the following drawings, wherein:

[0024] Figure 1 Shows the pathological morphology of the lung tissues of rats in each group (200×) according to an embodiment of the present invention. a is the control group; b is the model group; c is group A; d is group B; e is group I; f is group J. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0025] The solution of the present invention will be explained below in conjunction with embodiments. Those skilled in the art will understand that the following embodiments are only used to illustrate the present invention and should not be regarded as limiting the scope of the present invention. For those without specific technical or conditions noted in the embodiments, the techniques or conditions described in the literature in the art or according to the product specifications are followed. Those reagents or instruments without the manufacturer noted are all conventional products that can be obtained through commercial purchase.

[0026] Example 1

[0027] In this embodiment, the traditional Chinese medicine composition is prepared according to the following method:

[0028] 1. Formula composition:

[0029] Poria cocos 50 parts, Pinellia ternata (processed with Rhizoma Zingiberis Recens) 50 parts, Fructus Aurantii Immaturus 50 parts, Pericarpium Citri Reticulatae Viride 50 parts, Arisaema cum Bile 50 parts, Exocarpium Citri Rubrum 50 parts, Fructus Amomi 50 parts, Semen Amomi 25 parts, Semen Arecae 50 parts, Cortex Albiziae 50 parts, Medicated Leaven 50 parts, Caulis Perillae 50 parts, Rhizoma Zingiberis Recens 7.5 parts, Cryptotympana pustulata Fabricius 50 parts, Oroxylum indicum (L.) Kurz 50 parts, Magnolia officinalis Rehd. et Wils. 50 parts.

[0030] 2. Preparation method:

[0031] (1) Weigh according to the above formula. Fructus Aurantii Immaturus, Pericarpium Citri Reticulatae Viride, and Medicated Leaven are stir-fried with slow fire respectively until the surface color of the medicinal materials turns yellow, and set aside;

[0032] (2) After Magnolia officinalis Rehd. et Wils. is processed with the water decoction of Rhizoma Zingiberis Recens, set aside;

[0033] (3) Take half of the amount of Poria cocos, Fructus Amomi, and Arisaema cum Bile, pulverize them into fine powder of 140 meshes, sieve, and mix evenly, then set aside;

[0034] (4) Decoct the remaining nine medicinal materials in the formula and the remaining amount of the three medicinal materials of Poria cocos, Fructus Amomi, and Arisaema cum Bile twice with water, each time for 2 hours, combine the decoction liquids, filter, concentrate the filtrate to a thick paste with a relative density of 1.32 at 85 °C, mix it evenly with the fine powder prepared in step (3), dry, pulverize, make it into small granules, and fill them into capsules to obtain the product.

[0035] Example 2

[0036] In this embodiment, the traditional Chinese medicine composition is prepared according to the following method:

[0037] 1. Formula composition:

[0038] Pericarpium Citri Reticulatae Viride 50 parts, Fructus Aurantii Immaturus 50 parts, Caulis Perillae 50 parts, Magnolia officinalis Rehd. et Wils. 50 parts, Poria cocos 50 parts, Pinellia ternata (processed with Rhizoma Zingiberis Recens) 50 parts, Arisaema cum Bile 50 parts, Cryptotympana pustulata Fabricius 50 parts, Oroxylum indicum (L.) Kurz 50 parts, Rhizoma Zingiberis Recens 7.5 parts, and Medicated Leaven 50 parts.

[0039] 2. Preparation method:

[0040] (1) Weigh according to the above formula. Stir-fry Fructus Aurantii Immaturus, Pericarpium Citri Reticulatae Viride, and Medicated Leaven separately over a slow fire until the surface color of the medicinal materials turns yellow, and set aside.

[0041] (2) Prepare the medicinal materials of Magnolia officinalis with ginger water and set aside.

[0042] (3) Take half of the amount of Poria cocos, Amomum villosum, and Arisaema cum Bile each, pulverize them into fine powder No. 140, sieve, mix evenly, and set aside.

[0043] (4) Decoct the remaining four kinds of medicinal materials in the formula and the remaining amounts of the three kinds of medicinal materials of Poria cocos, Amomum villosum, and Arisaema cum Bile twice with water, each time for 2 hours. Combine the decoction liquids, filter, concentrate the filtrate to a thick paste with a relative density of 1.32 at 85°C, mix it evenly with the fine powder prepared in step (3), dry, pulverize, make it into small granules, and fill them into capsules to obtain the product.

[0044] Example 3

[0045] In this example, the traditional Chinese medicine composition is prepared according to the following method:

[0046] 1. Formula composition:

[0047] Poria cocos 60 parts, Pinellia ternata 60 parts, Fructus Aurantii Immaturus 60 parts, Pericarpium Citri Reticulatae Viride 60 parts, Arisaema cum Bile 60 parts, Exocarpium Citri Rubrum 60 parts, Amomum villosum 60 parts, Amomum kravanh 35 parts, Areca catechu 60 parts, Cortex Albiziae 60 parts, Medicated Leaven 60 parts, Caulis Perillae 60 parts, Zingiber officinale 8 parts, Cryptotympana pustulata Fabricius 60 parts, Oroxylum indicum (L.) Kurz 60 parts, Magnolia officinalis 60 parts.

[0048] 2. Preparation method:

[0049] (1) Weigh according to the above formula. Stir-fry Fructus Aurantii Immaturus, Pericarpium Citri Reticulatae Viride, and Medicated Leaven separately over a slow fire until the surface color of the medicinal materials turns yellow, and set aside.

[0050] (2) Prepare the medicinal materials of Magnolia officinalis with ginger water and set aside.

[0051] (3) Take half of the amount of Poria cocos, Amomum villosum, and Arisaema cum Bile each, pulverize them into fine powder No. 120, sieve, mix evenly, and set aside.

[0052] (4) Decoct the remaining nine kinds of medicinal materials in the formula and the remaining amounts of the three kinds of medicinal materials of Poria cocos, Amomum villosum, and Arisaema cum Bile twice with water, each time for 2 hours. Combine the decoction liquids, filter, concentrate the filtrate to a thick paste with a relative density of 1.28 at 85°C, mix it evenly with the fine powder prepared in step (3) and appropriate excipients, press into tablets, and coat with a film coating to obtain the tablets.

[0053] Example 4

[0054] In this example, the traditional Chinese medicine composition is prepared according to the following method:

[0055] 1. Formula composition:

[0056] Poria cocos 40 parts, Pinellia ternata (Thunb.) Breit. prepared with Rhizoma Zingiberis Recens 40 parts, Aurantii Fructus Immaturus 40 parts, Citri Reticulatae Viride Pericarpium 40 parts, Arisaema cum Bile 40 parts, Citri Reticulatae Exocarpium Rubrum 40 parts, Amomi Fructus 40 parts, Amomi kravanh Seed 15 parts, Arecae Catechu Semen 40 parts, Albiziae Cortex 40 parts, Medicata Fermentata 40 parts, Perillae Caulis 40 parts, Zingiberis Rhizoma Recens 6 parts, Cryptotympana pustulata Fabricius 40 parts, Oroxylum indicum (L.) Kurz 40 parts, Magnoliae Officinalis Cortex 40 parts.

[0057] 2. Preparation method:

[0058] (1) Weigh according to the above formula, stir-fry Aurantii Fructus Immaturus, Citri Reticulatae Viride Pericarpium, and Medicata Fermentata separately over a slow fire until the surface color of the medicinal materials turns yellow, and set aside;

[0059] (2) After preparing Magnoliae Officinalis Cortex with Zingiberis Rhizoma Recens water, set aside;

[0060] (3) Grind the twelve traditional Chinese medicines in the formula into fine powder of 80 meshes, sieve, and mix evenly.

[0061] (4) Add 35 parts by weight of refined honey to every 100 parts by weight of the powder; then mix evenly with an appropriate amount of purified water, refine the medicine, extrude the strips, make pills, dry, sieve the pills, and select the pills to make pills.

[0062] Example 5

[0063] In this example, the traditional Chinese medicine composition is prepared according to the following method:

[0064] 1. Formula composition:

[0065] Poria cocos 45 parts, Pinellia ternata (Thunb.) Breit. prepared with Rhizoma Zingiberis Recens 45 parts, Aurantii Fructus Immaturus 45 parts, Citri Reticulatae Viride Pericarpium 45 parts, Arisaema cum Bile 45 parts, Citri Reticulatae Exocarpium Rubrum 45 parts, Amomi Fructus 45 parts, Amomi kravanh Seed 20 parts, Arecae Catechu Semen 45 parts, Albiziae Cortex 45 parts, Medicata Fermentata 45 parts, Perillae Caulis 45 parts, Zingiberis Rhizoma Recens 7 parts, Cryptotympana pustulata Fabricius 45 parts, Oroxylum indicum (L.) Kurz 45 parts, Magnoliae Officinalis Cortex 45 parts.

[0066] 2. Preparation method:

[0067] (1) Weigh according to the above formula, stir-fry Aurantii Fructus Immaturus, Citri Reticulatae Viride Pericarpium, and Medicata Fermentata separately over a slow fire until the surface color of the medicinal materials turns yellow, and set aside;

[0068] (2) After preparing Magnoliae Officinalis Cortex with Zingiberis Rhizoma Recens water, set aside;

[0069] (3) Take half of the amount of Poria cocos, Amomi Fructus, and Arisaema cum Bile, grind them into fine powder of 130 meshes, sieve, and mix evenly, and set aside;

[0070] (4) Add the remaining amounts of the other nine medicinal materials in the formula and the three medicinal materials of Poria, Amomum villosum, and Arisaema cum Bile to water and decoct twice, each time for 2 hours. Combine the decoctions, filter, concentrate the filtrate to an extract with a temperature of 65°C and a relative density of 1.18, adjust the alcohol content to 60% with ethanol, take the supernatant, and recover ethanol and concentrate to a thick paste with a temperature of 85°C and a relative density of 1.28 - 1.32;

[0071] (5) Then granulate with the fine powder prepared in step (3), 135 parts of sucrose, and 65 parts of starch to obtain the product.

[0072] Comparative Example 1

[0073] The difference from Example 1 is that it does not contain Pericarpium Citri Reticulatae Viride.

[0074] Comparative Example 2

[0075] The difference from Example 1 is that it does not contain Caulis Perillae.

[0076] Comparative Example 3

[0077] The difference from Example 1 is that it does not contain Poria and Rhizoma Pinelliae Praeparatum.

[0078] Comparative Example 4

[0079] The difference from Example 1 is that Pericarpium Citri Reticulatae Viride and Fructus Aurantii Immaturus are replaced with Pericarpium Citri Reticulatae and Fructus Aurantii.

[0080] Comparative Example 5

[0081] The difference from Example 1 is that Caulis Perillae and Cortex Magnoliae Officinalis are replaced with Bupleuri Radix and Glycyrrhizae Radix et Rhizoma.

[0082] Comparative Example 6

[0083] The difference from Example 1 is that Poria and Rhizoma Pinelliae Praeparatum are replaced with Atractylodis Macrocephalae Rhizoma and Flos Farfarae.

[0084] Example 6

[0085] In this example, the intervention effect of the traditional Chinese medicine composition prepared in Example 1 on PM2.5-induced airway hyperresponsiveness in rats was studied.

[0086] I. Preparation of test drugs:

[0087] Group I (Example 1 of the present invention), Group J (Example 2 of the present invention), Group A (Comparative Example 1), Group B (Comparative Example 2), Group C (Comparative Example 3), Group D (Comparative Example 4), Group E (Comparative Example 5), Group F (Comparative Example 6), control group (distilled water).

[0088] Prepare the above raw materials into a pharmaceutical composition by the method of Example 1.

[0089] II. Test method

[0090] 1. Collection and treatment of PM2.5

[0091] On the rooftop of the No. 4 Teaching Building of Shaanxi University of Chinese Medicine, atmospheric PM2.5 was collected on a glass fiber membrane using a Tianhong high-volume sampler, and the sampling height was 20 m. The edge part of the glass fiber membrane carrying PM2.5 was cut off, cut into a size of 1 cm × 1 cm, and sub-packed into 50 ml centrifuge tubes. Pure water was added to 40 ml, and ultrasonic oscillation was carried out at low temperature for 60 min to elute PM2.5. It was filtered through a 1800-mesh sieve, and the filtrate was vacuum freeze-dried. The PM2.5 particles were collected and stored at 4°C for standby.

[0092] Preparation of PM2.5 solution: Before use, take 0.22 g of PM2.5 particles and dissolve them in 4 mL of physiological saline to prepare a suspension with a concentration of 0.05 g / mL, and ultrasonic oscillation was carried out for 10 min. The dosing dose of PM2.5 in this experiment was 10.8 mg / kg, and the volume of PM2.5 physiological saline suspension given each time was 20 μL / 100 g.

[0093] 2. Establishment of a high airway rat model induced by PM2.5

[0094] After 105 SD rats were adaptively fed for 1 week, they were randomly divided into a control group of 10 rats and a model group of 95 rats by simple randomization. Referring to the modeling method in the literature, the high airway model was constructed by nasal drip of PM2.5 solution to rats. A 10 - 100 μL pipette was used to suck the corresponding dose of PM2.5 suspension, and it was slowly dripped into the nasal cavity of the rats. The rats were poisoned every other day for 24 consecutive times, and the control group was dripped with an equal amount of physiological saline. During the poisoning and drug administration period, the hair, mental state, oral and nasal secretions of each group of rats were observed. After the last poisoning, the physical signs of the rats were observed; 5 rats in the model group were randomly selected to take lung tissue for pathological observation. A large number of inflammatory cell infiltrations were seen in the lung tissue, and the arrangement of muscle layer fibers was disordered, which was in line with the characteristics of the animal model of chronic pharyngitis, then it was judged that the modeling was successful.

[0095] 3. Grouping and drug administration

[0096] Ninety successfully modeled rats were grouped, with 10 rats in each group. The model group and the above control groups were given the same volume of sterile water. The remaining 8 groups of rats were continuously intragastrically administered the drugs of groups I, J and A, B, C, D, E, F at a dose of 0.48 g / kg for 14 days, once a day. After the last administration, the rats were fasted for 12 hours, anesthetized with 10% chloral hydrate, and blood was collected from the abdominal aorta; alveolar lavage fluid was collected, centrifuged at 3500 r at 4°C for 10 min, and the supernatant was taken to measure the activities of ACP, AKP, and LDH; the lung tissues were excised and fixed in 4% paraformaldehyde, dehydrated, paraffin-embedded, stained with HE, sealed with neutral resin, and the pathological changes were observed under a light microscope; RT-qPCR was used to measure the expression of IL-17 and Foxp3 mRNA in the lung tissues.

[0097] 4. Statistical methods

[0098] Data analysis was performed using SPSS 26.0 software. Measurement data that conformed to a normal distribution were expressed as (x±s). One-way ANOVA was used for comparisons among multiple groups. For pairwise comparisons, the LSD method was used when the data variances were homogeneous, and the Tamhane's T2 method was used when the variances were heterogeneous. A P value < 0.05 was considered statistically significant.

[0099] III. Experimental results

[0100] 1. Comparison of the general conditions of rats in each group

[0101] No obvious abnormalities occurred in the rats in the blank group throughout the experiment. Their hair, mental state, and behavioral performance were normal, there was no obvious secretion in the oral cavity and nasal cavity, and their breathing was normal. After 35 days of modeling, the rats in the model group showed mental sluggishness, less activity, yellow and dull hair, increased secretions in the nasal cavity and oral cavity, and rapid breathing accompanied by coughing and wheezing. With the administration time, the above symptoms and signs in the rats of groups I, J and A, B, C, D, E, F gradually alleviated.

[0102] 2. Morphological results of the lung tissues of rats in each group

[0103] Figure 1 This is the pathological morphology of the lung tissues of rats in each group of the present invention (200×). a is the control group; b is the model group; c is group A; d is group B; e is group I; f is group J. The lung tissue structure of the control group rats was clear, the alveolar cavity structure was complete, and there was no inflammatory cell infiltration in the interstitium; the lung tissue structure of the model group rats was damaged, the alveoli were collapsed, the alveolar septum was broken, and a large number of inflammatory cells were infiltrated. The phenomena of alveolar cavity bleeding and inflammatory cell infiltration in the rats of groups I and J were less severe than those in the model group and groups A and B, and the phenomenon in group I was the least severe. Thus, it is shown that the drug can reduce the pathological damage of the lungs of rats caused by PM2.5 and inhibit the production of pro-inflammatory cytokines.

[0104] 3. Determination of each biochemical index in BALF

[0105] The biochemical index results of bronchoalveolar lavage fluid (BALF) of rats in each group are shown in Table 1 below. In this experiment, the activities of cytotoxicity indexes ACP, AKP, and LDH were measured to observe the damage of lung cells and alveolar-capillary barrier in each group of animals. It can be seen from Table 1 that compared with the control group, the activities of ACP, AKP, and LDH in the BALF of rats in the model group were significantly increased (p < 0.01); compared with the model group, the activities of ACP, AKP, and LDH in the BALF of groups I, J, A, B, C, D, E, and F were significantly decreased (p < 0.01), but the decreases in groups I and J were obvious, and group I was the most obvious. Thus, it is indicated that the drug can reduce the level of cytotoxicity indexes in alveolar lavage fluid and effectively improve the permeability of alveolar cell membrane and alveolar epithelial-capillary membrane.

[0106] Table 1 Biochemical index levels in BALF of rats in each group

[0107]

[0108] Note: # p < 0.05 compared with the control group; * p < 0.05 compared with the model group

[0109] 4. IL-17, Foxp3 mRNA expression levels and Th17 / Treg ratio in lung tissues of rats in each group

[0110] The results of the expression levels of IL-17mRNA, Foxp3 mRNA, Th17 mRNA, and the ratio of Th17 mRNA to TregmRNA (denoted as Th17 / Treg) in the lung tissues of rats in each group are shown in Table 2. Compared with the control group, the expression level of IL-17mRNA and the Th17 / Treg ratio in the lung tissues of rats in the model group were significantly increased (P < 0.05), and the expression level of Foxp3 mRNA was significantly decreased (P < 0.05); compared with the model group, the expression level of IL-17mRNA and the Th17 / Treg ratio in each traditional Chinese medicine administration group were significantly decreased (P < 0.05), and the expression level of Foxp3 mRNA was significantly increased (P < 0.05), and group I had the best effect. It is indicated that the drug can inhibit the expression of pro-inflammatory factor IL-17, promote the differentiation of Treg, inhibit the generation of Th17, thus correct the Th17 / Treg imbalance, restore the body's immunity to homeostasis, and improve the high airway response caused by PM2.5.

[0111] Table 2 IL-17mRNA expression level, Foxp3 mRNA expression level and Th17 / Treg ratio in lung tissues of rats in each group

[0112]

[0113]

[0114] Note: # p < 0.05 compared with the control group; * p < 0.05 compared with the model group

[0115] IV. Experimental Conclusions

[0116] The composition of the present invention can effectively improve the permeability of alveolar cell membranes and alveolar epithelial-capillary membranes, inhibit the expression of pro-inflammatory factor IL-17, promote Treg differentiation, inhibit Th17 generation, thereby correcting the Th17 / Treg imbalance, restoring the body's immune homeostasis, and improving the lung injury caused by the high airway response induced by PM2.5.

[0117] In the description of this specification, the description referring to terms such as "one embodiment", "some embodiments", "examples", "specific examples", or "some examples", etc. means that the specific features, structures, materials, or characteristics described in connection with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials, or characteristics described can be combined in a suitable manner in any one or more embodiments or examples. In addition, without contradiction, those skilled in the art can combine and combine the different embodiments or examples described in this specification and the features of different embodiments or examples.

[0118] Although the embodiments of the present invention have been shown and described above, it can be understood that the above embodiments are exemplary and should not be construed as limiting the present invention. Those of ordinary skill in the art can make changes, modifications, substitutions, and variations to the above embodiments within the scope of the present invention.

Claims

1. Use of a composition in the preparation of a medicament, characterized in that, The drug is used for preventing or treating lung injury caused by inhaling PM2.5; The composition includes: 40 - 60 parts of immature tangerine peel, 40 - 60 parts of bitter orange, 40 - 60 parts of perilla stem, 40 - 60 parts of magnolia bark, 40 - 60 parts of poria cocos, 40 - 60 parts of prepared pinellia, 40 - 60 parts of arisaema cum bile, 40 - 60 parts of cicada slough, 40 - 60 parts of semen oroxylis, 6 - 8 parts of ginger, and 40 - 60 parts of medicated leaven.

2. The use according to claim 1, wherein The composition consists of the following substances: 40 - 60 parts of poria cocos, 40 - 60 parts of prepared pinellia, 40 - 60 parts of bitter orange, 40 - 60 parts of immature tangerine peel, 40 - 60 parts of arisaema cum bile, 40 - 60 parts of tangerine peel, 40 - 60 parts of amomum villosum, 15 - 35 parts of fructus amomi kravanh, 40 - 60 parts of areca nut, 40 - 60 parts of cortex albiziae, 40 - 60 parts of medicated leaven, 40 - 60 parts of perilla stem, 6 - 8 parts of ginger, 40 - 60 parts of cicada slough, 40 - 60 parts of semen oroxylis, and 40 - 60 parts of magnolia bark.

3. The use according to claim 1 or 2, characterized in that, The composition is used for alleviating damaged lung tissue structure, alveolar collapse, alveolar septum rupture and / or inflammatory cell infiltration.

4. The use according to claim 1 or 2, characterized in that, The composition is used for reducing the activities of serum acid phosphatase, alkaline phosphatase and lactate dehydrogenase in lung tissue cells.

5. The use according to claim 1 or 2, characterized in that, The composition is used for reducing the expression level of IL-17mRNA in lung tissue, reducing the ratio of the expression levels of Th17 mRNA and Treg mRNA, and / or increasing the expression level of Foxp3 mRNA.

6. The use according to claim 1 or 2, characterized in that, The dosage form of the drug is pill, tablet or capsule.

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