Traditional chinese medicine composition for treating lung inflammation related diseases and use thereof

Abstract

Disclosed is a traditional Chinese medicine composition for treating lung inflammation related diseases, comprising glycyrrhizic acid, baicalein, and 6-gingerol. The traditional Chinese medicine composition is based on a combination of effective components of various traditional Chinese medicines, and can play a multi-target and multi-level synergistic role. The multi-component combination can overcome the limited curative effect, adverse reaction and drug resistance of single-component treatment, and has no toxic or side effects in an effective dose range. Therefore, the safety of clinical medication is ensured, and especially for patients who are not suitable for hormones, the clinical application range is expanded. In addition, the traditional Chinese medicine effective component composition has clear components and clear interactions among components, and has higher efficacy and safety than traditional Chinese medicine compounds with complex components.

Description

A traditional Chinese medicine composition for treating diseases related to lung inflammation and its use Technical Field

[0001] The present invention relates to the field of pharmaceutical chemistry, and in particular to a traditional Chinese medicine composition for treating and / or preventing diseases related to lung inflammation and uses thereof. Background Art

[0002] Acute lung injury (ALI) is a severe clinical disease characterized by respiratory distress, refractory hypoxemia, and non-cardiogenic pulmonary edema. Further aggravation can develop into acute respiratory distress syndrome (ARDS), the pathological manifestation of which is extensive lung inflammation and death or dysfunction of alveolar epithelial cells and / or pulmonary capillary endothelial cells, leading to destruction of the alveolar-capillary barrier.

[0003] ALI / ARDS has a clinically high in-hospital mortality rate of 30%-50%, particularly in the context of the global outbreak of COVID-19, which has seen sporadic outbreaks. Currently, glucocorticoids are the primary treatment for ALI, achieving anti-inflammatory effects through immunosuppression. However, glucocorticoids can cause a variety of toxic side effects, including infection, gastrointestinal bleeding, electrolyte imbalances, hypertension, and hyperglycemia, significantly limiting their clinical application. Given the rapid spread and difficulty in preventing respiratory infections, the development of effective and safe treatments for ALI / ARDS is an urgent need.

[0004] Modern research confirms that ALI / ARDS occurs when pathogenic factors activate multiple inflammatory cells, releasing a series of inflammatory mediators. These inflammatory mediators can further activate inflammatory cells, releasing more inflammatory mediators or cytokines in an autocrine or paracrine manner, leading to a cascade of inflammation and excessive lung damage. LPS is a component of the outer membrane of Gram-negative bacteria. Its primary pathogen is lipopolysaccharide. Upon entry into the body, it activates macrophages to release pro-inflammatory factors, which then attract and activate polymorphonuclear neutrophils, which then seize in the lungs, generating a localized inflammatory response and causing ALI. This damages the pulmonary vascular endothelium, increasing its permeability and ultimately causing pulmonary edema and progressive gas exchange impairment. These changes are consistent with the pathological process of ALI / ARDS.

[0005] The active ingredients of traditional Chinese medicine are natural ingredients derived from plants and play a certain therapeutic role in the treatment of ALI. For example, the active ingredients of traditional Chinese medicine such as phenols, terpenes, phenylpropanoids and alkaloids have the effects of reducing inflammatory responses, resisting oxidative stress, regulating the body's immunity, and improving alveolar-capillary barrier dysfunction. In addition, compared with commonly used clinical therapeutic drugs, the active ingredients of traditional Chinese medicine also have unique advantages such as low toxicity and side effects and high safety. However, to date, there has been no report in the prior art of a traditional Chinese medicine composition that can safely and effectively treat lung inflammation-related diseases caused by various factors (e.g., acute lung injury, acute respiratory distress syndrome, etc.).

[0006] Summary of the Invention

[0007] In view of the deficiencies in the prior art, one of the objectives of the present invention is to provide a Chinese medicine composition for treating and / or preventing diseases related to lung inflammation.

[0008] The Chinese medicine composition for treating and / or preventing diseases related to lung inflammation of the present invention is achieved by the following technical solutions:

[0009] A traditional Chinese medicine composition for treating diseases related to lung inflammation, comprising glycyrrhizic acid, baicalein and 6-shogaol.

[0010] According to the traditional Chinese medicine composition of the present invention, wherein the traditional Chinese medicine composition comprises the following active ingredients: glycyrrhizic acid, baicalein and 6-shogaol. Preferably, the traditional Chinese medicine composition comprises the following active ingredients: glycyrrhizic acid, baicalein and 6-shogaol.

[0011] According to the traditional Chinese medicine composition of the present invention, the molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is (1-16): (1-16): (1-16).

[0012] According to the traditional Chinese medicine composition of the present invention, the molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is (4-12): (1-8): (1-12).

[0013] According to the traditional Chinese medicine composition of the present invention, the molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is (6-10): (1-4): (1-8).

[0014] According to the traditional Chinese medicine composition of the present invention, the molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is (7-9): (1-2): (2-6).

[0015] According to the traditional Chinese medicine composition of the present invention, the molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is 8:1:4.

[0016] According to the traditional Chinese medicine composition of the present invention, the molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is 1:1:1.

[0017] According to the traditional Chinese medicine composition of the present invention, the molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is 2:1:2.

[0018] According to the traditional Chinese medicine composition of the present invention, the molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is 8:1:8.

[0019] According to the traditional Chinese medicine composition of the present invention, the molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is 16:1:16.

[0020] According to the traditional Chinese medicine composition of the present invention, the molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is 1:2:2.

[0021] According to the traditional Chinese medicine composition of the present invention, the molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is 2:2:1.

[0022] According to the traditional Chinese medicine composition of the present invention, the molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is 8:2:16.

[0023] According to the traditional Chinese medicine composition of the present invention, the molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is 16:2:8.

[0024] According to the traditional Chinese medicine composition of the present invention, the molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is 1:8:8.

[0025] According to the traditional Chinese medicine composition of the present invention, the molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is 2:8:16.

[0026] According to the traditional Chinese medicine composition of the present invention, the molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is 8:8:1.

[0027] According to the traditional Chinese medicine composition of the present invention, the molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is 16:8:2.

[0028] According to the traditional Chinese medicine composition of the present invention, the molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is 1:16:16.

[0029] According to the traditional Chinese medicine composition of the present invention, the molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is 2:16:8.

[0030] According to the traditional Chinese medicine composition of the present invention, the molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is 8:16:2.

[0031] According to the traditional Chinese medicine composition of the present invention, the molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is 16:16:1.

[0032] According to the Chinese medicine composition of the present invention, wherein, the Chinese medicine composition further comprises a pharmaceutically acceptable carrier. Generally, the "pharmaceutically acceptable carrier" refers to a medium generally acceptable in the art for delivering a biologically active substance to a cell or an acceptable medium for delivering a biologically active substance to an animal (particularly a mammal), including adjuvants, excipients or solvents, such as diluents, preservatives, fillers, flow control agents, penetration enhancers, disintegrants, wetting agents, emulsifiers, suspending agents, sweeteners, lubricants and dispersants, etc. The choice of pharmaceutically acceptable carrier depends on the mode of administration and the nature of the dosage form.

[0033] According to the traditional Chinese medicine composition of the present invention, the traditional Chinese medicine composition is administered orally, intravenously, locally, by inhalation or spraying, sublingually, transdermally or rectally, or by other means.

[0034] According to the traditional Chinese medicine composition of the present invention, the dosage form of the traditional Chinese medicine composition is aerosol, ointment, dripping pill, soft capsule, granule, tablet, syrup or nano preparation, etc.

[0035] A second object of the present invention is to provide the use of the above-mentioned Chinese medicine composition in the preparation of a medicine or medicament for treating and / or preventing diseases related to lung inflammation.

[0036] A third object of the present invention is to provide a drug or medicament for treating and / or preventing diseases related to lung inflammation, wherein the drug or medicament comprises the above-mentioned Chinese medicine composition.

[0037] According to the medicine or medicament of the present invention, wherein, the medicine or medicament further comprises a pharmaceutically acceptable carrier. Generally, the "pharmaceutically acceptable carrier" refers to a medium generally acceptable in the art for delivering a biologically active substance to a cell or an acceptable medium for delivering a biologically active substance to an animal (particularly a mammal), including an adjuvant, excipient or solvent, such as a diluent, preservative, filler, flow control agent, permeation promoter, disintegrant, wetting agent, emulsifier, suspending agent, sweetener, lubricant and dispersant, etc. The choice of pharmaceutically acceptable carrier depends on the mode of administration and the nature of the dosage form.

[0038] According to the drug or pharmaceutical agent of the present invention, the drug or pharmaceutical agent is administered orally, intravenously, locally, by inhalation or spraying, sublingually, transdermally or rectally, or by other means.

[0039] According to the medicine or pharmaceutical agent of the present invention, the dosage form of the medicine or pharmaceutical agent is an aerosol, ointment, pill, soft capsule, granule, tablet, syrup or nano preparation, etc.

[0040] It should be noted that the carriers, administration methods and dosage forms that can be added to the Chinese herbal composition of the present invention are not limited by the above contents.

[0041] The "lung inflammation-related diseases" described in this invention include pneumonia, acute lung injury, and lung diseases with pathological characteristics consistent with pneumonia and / or acute lung injury caused by various factors. The "pneumonia and acute lung injury caused by various factors" described in this invention refers to lung diseases with pathological characteristics consistent with pneumonia and / or acute lung injury caused by infectious factors (viruses or bacteria) and non-infectious factors (foreign body aspiration), but is not limited to these.

[0042] The advantages of the present invention are:

[0043] 1. The Chinese medicine composition of the present invention is used to treat acute lung injury (ALI) caused by various reasons. Currently, there is a lack of drugs for this disease in clinical practice, and the present invention can fill this gap.

[0044] 2. The Chinese medicine composition of the present invention is based on a combination of multiple active ingredients from traditional Chinese medicines, achieving synergistic effects at multiple targets and levels. This multi-ingredient combination overcomes the limited efficacy, adverse reactions, and drug resistance of single-ingredient treatments. Animal studies have shown that the present invention significantly improves the pathological damage of LPS-induced ALI and has a significant inhibitory effect on pulmonary edema, effectively preventing deaths from respiratory failure caused by pulmonary edema in clinical settings.

[0045] 3. The components and combinations contained in the Chinese medicine composition of the present invention have been proven by a large number of experimental studies to have no toxic side effects within the effective dosage range, thereby ensuring the safety of clinical use, especially for patients who are not suitable for hormones, thereby expanding the scope of clinical use.

[0046] 4. The present invention is a composition of effective ingredients of traditional Chinese medicine, with clear ingredients and clear interactions between ingredients. Its efficacy and safety are higher than those of traditional Chinese medicine compounds with complex ingredients. BRIEF DESCRIPTION OF THE DRAWINGS

[0047] FIG1 shows the leukocyte counts in BALF of mice in each drug-treated group.

[0048] FIG2 shows the pathological morphology of lung tissues of mice in each drug-treated group (HE staining, 200×). DETAILED DESCRIPTION

[0049] The present invention will be further described below with reference to experimental examples. The following experimental examples are descriptive and not restrictive, and the scope of protection of the present invention cannot be limited based on the following experimental examples.

[0050] The information of the materials used in the experimental examples of the present invention is as follows:

[0051] Glycyrrhizic acid, baicalein, and 6-shogaol were purchased from MedChemExpress (MCE). Glycyrrhizic acid (HPLC purity ≥ 98.0%), lot number: HY-NO184-252139; baicalein (HPLC purity ≥ 98.84%), lot number: HY-N0196-24282; and 6-shogaol (HPLC purity ≥ 99.78%), lot number: HY-14616-150779. Lipopolysaccharides (from Escherichia coli O55:B55) were purchased from Sigma (USA), lot number: 039M4004V.

[0052] RAW264.7 (mouse monocytic macrophage leukemia cells), Catalog No. CL-0190; THP-1 (human monocytic leukemia cells), Catalog No. CL-0233; RAW264.7 cells were cultured in DMEM high-glucose medium supplemented with 10% fetal bovine serum (FBS) and 1% penicillin-streptomycin (P / S); THP-1 cells were cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum (FBS), 1% penicillin-streptomycin (P / S), and 0.05 mM β-mercaptoethanol. All cells and culture reagents were purchased from Wuhan Punosai Life Science Technology Co., Ltd. The nitric oxide assay kit was purchased from Shanghai Biotech Co., Ltd. (catalog number S0024). Mouse TNF-α, IL-6, and IL-1β ELISA kits were purchased from Cohesion Biosciences (UK) (catalog numbers CK5E65C, CK7E14B, and CK7E88C). The human IL-6 ELISA kit was purchased from Cohesion Biosciences (UK) (catalog number CEK1239). Male Balb / c mice were purchased from Yusibeifu (Beijing) Biotechnology Co., Ltd.

[0053] The following is a detailed explanation of the therapeutic and / or preventive effects of the Chinese medicine composition of the present invention on pneumonia and acute lung injury with reference to experimental examples.

[0054] Experimental Example 1: Analysis of the synergistic effects of various components in a traditional Chinese medicine composition

[0055] The NICM Health Research Institute (NICM HRI) reported that luteolin, glycyrrhizic acid, andrographolide, baicalein, 6-shogaol, and tetrandrine inhibited LPS-induced NO release in RAW264.7 cells. The present invention further demonstrated that the combination of glycyrrhizic acid, baicalein, and 6-shogaol exhibited a synergistic effect. The following information includes in vitro experiments and the use of different mathematical models to predict and validate the interactions between these three traditional Chinese medicine components.

[0056] RAW264.7 cells 1×10 6 / ml was inoculated into a 96-well cell culture plate. After culturing for 24 hours, four groups of drugs, including glycyrrhizic acid (100 μM, containing 0.1% DMSO), baicalein (100 μM, containing 0.1% DMSO), 6-shogaol (100 μM, containing 0.1% DMSO), and a three-component composition (a composition with a molar ratio of glycyrrhizic acid: baicalein: 6-shogaol of 1:1:1, totaling 100 μM, containing 0.1% DMSO) were serially diluted. After the cells were pre-treated with the serial dilution solution for 2 hours, RAW264.7 cells were treated with LPS (50 ng / ml) for 24 hours. The cell supernatant was aspirated, the NO release level in the supernatant was measured, and the IC of the four groups of drugs for inhibiting NO release was calculated. 50 value.

[0057] Table 1: Effects of different concentration gradients of glycyrrhizic acid, baicalein and 6-shogaol on the NO production rate of RAW264.7 cells induced by LPS

[0058] * NO production at LPS stimulation at a concentration of 0 was set as 100%, and NO production in cells without LPS stimulation was set as 0%. All NO production results are expressed as mean ± standard deviation.

[0059] According to the above table, the IC values ​​of glycyrrhizic acid, baicalein and 6-shogaol were calculated. 50 The values ​​(concentration at which NO generation is 50%) were 78.78±11.93 μM, 11.30±1.32 μM and 3.23±0.42 μM, respectively.

[0060] Table 2: Effects of three-component compositions at different concentration gradients on LPS-induced NO production in RAW264.7 cells

[0061] * NO production under LPS stimulation at a dose of 0 was set as 100%, and NO production in cells without LPS stimulation was set as 0%. All NO production results are expressed as mean ± standard deviation.

[0062] According to the above table, the IC value of the three-component composition of glycyrrhizic acid, baicalein and 6-shogaol was calculated. 50 The value (concentration at which NO generation is 50%) was 2.85±0.14 μM.

[0063] The dose-effect relationships of the three individual components and the three-component combination were imported into CalcuSyn software 2.0 (Biosoft, USA). Using the Chou-Talalay mathematical model, a Fa-CI plot was generated. The Fa-CI plot reflects the relationship between the CI value and the effective level of a specific biological indicator (i.e., NO inhibition). The CI value can be used to quantitatively determine the strength and nature of drug-drug interactions: a CI greater than 1 indicates antagonism, a CI = 1 indicates additive action, and a CI < 1 indicates synergism.

[0064] Table 3: Analysis of synergistic effects of glycyrrhizic acid, baicalein and 6-shogaol

[0065] Conclusion: The experimental results are shown in Tables 1, 2, and 3. The IC 50 The values ​​were lower than the IC values ​​of each single component 50 When all drugs achieved a 50% inhibition rate on LPS-induced NO in the supernatant of RAW264.7 cells, the drug concentrations required for the three-component group were lower than those required for each single component. Furthermore, the CI value of the three-component group was <1, indicating that the three-component combination had a certain synergistic effect.

[0066] Experimental Example 2: Drug Preparation

[0067] 1. Preparation of the test solutions of Experimental Examples 3 and 4

[0068] In Experimental Examples 3 and 4 of the present invention, a total of 16 drug administration groups were set up, and the mass of the effective components of the Chinese medicinal liquid in each drug administration group was weighed strictly according to Table 4.

[0069] Table 4: Weight of each active ingredient in each Chinese medicine composition in Experimental Examples 3 and 4

[0070] Weigh each drug according to Table 4 and place it into a 15mL centrifuge tube. Add 10mL of dimethyl sulfoxide (DMSO) solvent, place the tube in an ultrasonic cleaner, and sonicate thoroughly to fully dissolve the drug. Add 10μL of the above-dissolved drug-in-DMSO solution to 9.99mL of pre-prepared complete medium, so that the final DMSO volume in each test solution accounts for 0.1% of the total drug solution volume. At the same time, the drug concentration in each test solution also reaches the pre-determined dosing concentration (see Table 5).

[0071] Table 5: Molar concentrations of active ingredients of each Chinese medicine in the test solution in the experimental examples 3 and 4 drug administration groups

[0072] 2. Preparation of LPS

[0073] (1) Preparation of LPS in Experimental Examples 3 and 4: Weigh 1 mg of LPS and dissolve it in 1 mL of complete culture medium to prepare a 1 mg / ml LPS stock solution, which was subsequently diluted to 50 ng / ml for subsequent cell experiments.

[0074] (2) LPS preparation in Experimental Examples 5 and 6: 4 mg of LPS was weighed and dissolved in 1 ml of normal saline to prepare a 4 mg / ml LPS stock solution, which was subsequently diluted to 0.4 mg / ml for subsequent animal experiments.

[0075] 3. Preparation of the three-component test solution of Experimental Examples 5 and 6

[0076] Accurately weigh 164.59 mg of glycyrrhizic acid, 6.76 mg of baicalein, and 27.64 mg of 6-singerol, fully dissolve them in 1 mL of DMSO, and then add 4 mL of PEG300 to mix evenly. 0.5 mL of Tween-80 was added to the above system, mixed evenly, and then 4.5 mL of normal saline was added to make the volume 10 mL to obtain a 10 mL (20 mM glycyrrhizic acid, 2.5 mM baicalein, 10 mM 6-singerol) solution system with a molar ratio of glycyrrhizic acid: baicalein: 6-singerol of 8:1:4, which was used for subsequent animal experiments.

[0077] Experimental Example 3: Inhibitory effect of a Chinese herbal composition on the release of inflammatory mediators and inflammatory factors in RAW264.7 cells

[0078] RAW264.7 cells were collected at 1×10 5 / ml density was seeded in a 24-well plate. After culturing for 24 hours, RAW264.7 cells were treated with the test solution in groups 1-16 for 2 hours, and then added with complete medium containing 50 ng / mL LPS configured in Experimental Example 2 and cultured for 24 hours. The cell supernatant was collected. The release of NO, TNF-α, and IL-6 in the cell supernatant was detected using a nitric oxide reagent detection kit, a mouse TNF-α detection kit, and a mouse IL-6 detection kit, respectively. The results of the average release of NO, TNF-α, and IL-6 from RAW264.7 cells are shown in Table 6. The results in Table 6 were imported into IBM SPSS Statistics Software (4.0, USA) and variance analysis was performed on the three indicators one by one. The specific results are shown in Tables 7 to 9.

[0079] Experimental results

[0080] Table 6: Average release of inflammatory mediators and inflammatory factors in the cell supernatant of each drug group (n≥3)

[0081] Table 7: ANOVA analysis of the average NO release in the supernatant of RAW264.7 cells in treatment groups 1-16

[0082] Table 8: Variance analysis of the average release of IL-6 in the supernatant of RAW264.7 cells in treatment groups 1-16

[0083] Table 9: Variance analysis of the average release of TNF-α in the supernatant of RAW264.7 cells in treatment groups 1-16

[0084] According to Table 7, the variance analysis of the release amount of NO in the supernatant of RAW264.7 cells showed that in terms of the level of inhibition of the release of inflammatory mediator NO, 5 drug-treated groups showed a significant inhibitory effect on the release of NO, namely: drug-treated group 16, drug-treated group 8, drug-treated group 7, drug-treated group 15, and drug-treated group 4.

[0085] According to Table 8, in terms of inhibiting the release level of the inflammatory factor IL-6, the administration group 8 can effectively reduce the release level of the inflammatory factor IL-6 in the supernatant of RAW264.7 cells.

[0086] According to Table 9, the three medication groups, medication group 8, medication group 7 and medication group 16, all had a significant inhibitory effect on the release of the inflammatory factor TNF-α.

[0087] Experimental Example 4: Inhibitory effect of a Chinese herbal composition on the release of inflammatory factor IL-6 from THP-1 cells

[0088] Human monocytic THP-1 cells were cultured in RPMI-1640 medium containing 10% fetal bovine serum, 100 U / mL streptomycin, and 100 μg / mL penicillin in a cell culture incubator at 37°C and 5% CO2. THP-1 cells in the logarithmic growth phase were selected and induced to become M0 macrophages using phorbol esters. The culture medium was then replaced and the THP-1 cells, which had been successfully induced into M0 macrophages, were treated with drugs from groups 1-16 for 0.5 h. The cells were then treated with LPS for 24 h. The cell supernatants were collected and IL-6 release was measured using a human IL-6 detection kit. The experimental results are shown in Table 10. The results in Table 10 were imported into IBM SPSS Statistics Software (4.0, USA) for analysis of variance, resulting in Table 11.

[0089] Experimental results

[0090] Table 10: Average release of inflammatory factor IL-6 in the cell supernatant of each group (n≥3)

[0091] Table 11: Variance analysis of the average IL-6 release in the cell supernatant after the human monocytic cell line THP-1 was induced to differentiate into M0 macrophages in each group

[0092] Note: The inhibitory effect on the IL-6 release level in THP-1 supernatant decreases from top to bottom.

[0093] The results in Table 11 show that there are 12 dosing groups that can effectively inhibit the human monocytic cell line THP-1 from inducing differentiation into M0 macrophages and releasing IL6, namely: dosing group 6, dosing group 7, dosing group 8, dosing group 9, dosing group 11, dosing group 14, dosing group 10, dosing group 5, dosing group 2, dosing group 1, dosing group 3 and dosing group 16.

[0094] Conclusion: According to Experimental Examples 3 and 4, the Chinese medicine composition of the present invention can effectively inhibit the release of inflammatory factors and inflammatory mediators by RAW264.7 cells and human monocytic cell line THP-1, and has good potential for the treatment of acute lung injury.

[0095] Experimental Example 5: Improvement of the Chinese Herbal Composition on Acute Lung Injury Model in Mice

[0096] Construction of mouse acute lung injury model: After anesthetizing mice with isoflurane, LPS (1 mg / kg) was instilled into one nasal cavity. After instillation, the mice were quickly placed upright and returned to their original cage after waking up to complete the model.

[0097] The experiment was divided into a control group (no acute lung injury was induced, and an equal volume of normal saline was administered orally), a model group (acute lung injury was induced, and an equal volume of normal saline was administered orally), a three-component group (acute lung injury was induced, and the three-component test solution prepared in Item 3 of Experimental Example 2 was administered orally, 398 mg / kg), and a dexamethasone group (acute lung injury was induced, and the drug was administered by intraperitoneal injection at a dose of 5 mg / kg. All drugs were administered 0.5 h after the LPS-induced ALI model in mice.

[0098] 24 hours after model establishment, the mice were anesthetized with sodium pentobarbital and sacrificed by exsanguination via the abdominal aorta. Lung tissue was dissected and weighed, and the lung coefficient (lung tissue weight / mouse body weight) was calculated. The right upper lobe of the mouse lung was fixed in formalin, pathologically sectioned, and stained with HE to observe pathological changes. The middle and lower lobes of the right lung of the mouse were weighed (wet weight), placed in a 60°C oven to constant weight, and weighed (dry weight). The wet-to-dry weight ratio (wet weight / dry weight, W / D) was calculated. The experimental results are shown in Table 12. The right lung bronchus was ligated, and the left lobe of the mouse lung was removed. After lavage three times with 0.8 mL of PBS, the alveolar lavage fluid (BALF) was recovered. The total white blood cell count and total protein concentration were determined using an automatic cell counter. The experimental results are shown in Table 12 and Figure 1.

[0099] Experimental results

[0100] Compared with the model group, the three-component group could significantly reduce the lung index and wet-to-dry weight ratio of ALI mice

[0101] (P<0.05), and the three-component group could also effectively reduce the white blood cell count and protein concentration in the BALF of ALI mice (P<0.01).

[0102] Conclusion: The three-component group can effectively improve the damage of lung epithelium and vascular endothelium in LPS-induced ALI mice, effectively reduce the increase of lung tissue permeability, and thus alleviate pulmonary edema and the leakage of leukocytes and proteins.

[0103] Table 12: Effects of each group of drugs on relevant indicators of LPS-induced ALI mice

[0104] Note: Compared with the control group # P<0.05, ## P<0.01; compared with the model group * P<0.05, ** P<0.01.

[0105] Experimental Example 6: Effect of a Chinese herbal composition on improving lung inflammation in a mouse model of acute lung injury

[0106] The levels of inflammatory factors IL-1, IL-6, and TNF- in BALF were determined strictly according to the instructions of the inflammatory factor detection kit.

[0107] The right upper lobe of the mouse lung was fixed with a tissue fixative for 72 hours, embedded in paraffin, sectioned, dehydrated, and stained to prepare HE-stained sections. Lung tissue lesions were observed under a microscope. The experimental results are shown in Table 13 and Figure 2.

[0108] Experimental results

[0109] Compared with the model group, the three-component group could significantly reduce the levels of IL-1, IL-6, and TNF- in the BALF of LPS-induced ALI mice (P<0.01 or P<0.05); lung tissue pathological sections showed that compared with the model group, the three-component group significantly improved the number of neutrophils and monocytes in the lungs, and the alveolar wall thickening lung tissue pathology score was significantly improved compared with the model group (P<0.05).

[0110] Conclusion: The three-component group can significantly reduce the levels of inflammatory factors IL-1, IL-6, and TNF- in BALF, suggesting that the three-component group can effectively inhibit the infiltration, activation, and release of inflammatory factors of inflammatory cells in lung tissue, thereby inhibiting the inflammatory storm and improving LPS-induced ALI in mice.

[0111] Table 13: Effects of each group of drugs on inflammatory factors in BALF of LPS-induced ALI mice

[0112] Note: Compared with the control group # P<0.05, ## P<0.01; compared with the model group * P<0.05, ** P<0.01.

[0113] The above is only a preferred embodiment of the present invention. It should be pointed out that ordinary technicians in this technical field can make several improvements and supplements without departing from the method of the present invention, such as changing the ratio of the three effective ingredients of traditional Chinese medicine. These improvements and supplements should also be within the scope of protection of the present invention.

Claims

1. A Chinese medicine composition for treating diseases related to pulmonary inflammation, comprising glycyrrhizic acid, baicalein and 6-shogaol.

2. The Chinese medicine composition according to claim 1, in, The molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is (1-16): (1-16): (1-16).

3. The Chinese medicine composition according to claim 1 or 2, in, The molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is (4-12): (1-8): (1-12).

4. The Chinese medicine composition according to claim 1 or 2, in, The molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is (6-10): (1-4): (1-8).

5. The Chinese medicine composition according to claim 1 or 2, in, The molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is (7-9): (1-2): (2-6).

6. The Chinese medicine composition according to claim 1 or 2, in, The molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is 8:1:4; or The molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is 1:1:1; or The molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is 2:1:2; or The molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is 8:1:8; or The molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is 16:1:16; or The molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is 1:2:2; or The molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is 2:2:1; or The molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is 8:2:16; or The molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is 16:2:8; or The molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is 1:8:8; or The molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is 2:8:16; or The molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is 8:8:1; or The molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is 16:8:2; or The molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is 1:16:16; or The molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is 2:16:8; or The molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is 8:16:2; or The molar ratio of glycyrrhizic acid, baicalein and 6-shogaol in the traditional Chinese medicine composition is 16:16:

1.

7. The Chinese medicine composition according to claim 1 or 2, in, The traditional Chinese medicine composition also comprises a pharmaceutically acceptable carrier.

8. The Chinese medicine composition according to claim 1 or 2, in, The Chinese medicine composition is administered orally, intravenously, locally, by inhalation or spraying, sublingually, transdermally or rectally.

9. The Chinese medicine composition according to claim 1 or 2, in, The dosage form of the traditional Chinese medicine composition is aerosol, ointment, dripping pill, soft capsule, granule, tablet, syrup or nano preparation.

10. Use of the Chinese medicine composition according to any one of claims 1 to 9 in the preparation of a drug or medicament for treating and / or preventing diseases related to pulmonary inflammation.

11. A medicine or agent for treating and / or preventing diseases related to pulmonary inflammation, wherein the medicine or agent comprises the Chinese medicine composition according to any one of claims 1 to 9.

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