Compound having Anti-inflammatory activity, preparation method therefor and use thereof

Abstract

Disclosed are a compound having anti-inflammatory activity, a preparation method therefor and the use thereof. According to the present invention, compounds 1-3, which have anti-inflammatory activity, are obtained from a metabolite of the Penicillium commune strain GIZ45-A73 for the first time. The metabolite of the Penicillium commune strain GIZ45-A73 of the present invention, which is obtained from the intestinal tract of Hepialus, is significantly different from metabolites of Penicillium commune strains from other sources, and is an important resource for discovering active metabolites.

Description

Compound with anti-inflammatory activity and preparation method and application thereof Technical field:

[0001] The present invention belongs to the technical field of natural products, and in particular relates to a bat moth intestinal tract-derived fungal strain and a compound with anti-inflammatory activity produced by fermentation thereof. Background technology:

[0002] Inflammation is a protective response of the body that clears external stimuli and maintains homeostasis during infection or injury. It is characterized by redness, swelling, heat, pain, and functional impairment. Short-term inflammation helps clear inflammatory substances and promote recovery, making it a key step in the body's self-repair. However, excessive or chronic inflammation can lead to various diseases, such as cardiovascular dysfunction, metabolic disorders, autoimmune diseases, rheumatoid arthritis, cancer, and sepsis, posing a serious threat to human health. Currently, the main drugs used to treat inflammatory diseases include steroidal and nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs have varying degrees of side effects, such as NSAIDs causing alterations in the hematopoietic system, cardiovascular damage, and asthma, posing a significant threat to human health. Therefore, the search for safer and more effective anti-inflammatory drugs from natural products is of great significance for safeguarding human life and health.

[0003] Fungal metabolites are abundant and represent an important natural resource for the development of modern pharmaceutical formulations. Nature is rich in fungal resources, and fungi possess a vast gene pool, potentially allowing for the synthesis of novel and highly active compounds. This makes them an important avenue for developing naturally occurring active pharmaceutical ingredients.

[0004] Summary of the invention:

[0005] The purpose of the present invention is to provide a bat moth intestinal tract-derived fungus and a compound with significant anti-inflammatory activity obtained by fermenting the fungus.

[0006] The present invention provides a bat moth intestinal-derived fungus Penicilium commune GIZ45-A73, which has been deposited in the Guangdong Provincial Microbiological Culture Collection Center (GDMCC) on March 18, 2024, address: Institute of Microbiology, Guangdong Academy of Sciences, Guangdong, China, Postal Code: 510070, and the deposit number is GDMCC NO: 64414.

[0007] The present invention provides an anti-inflammatory compound derived from the bat moth intestinal fungus Penicilium commune GIZ45-A73 or a pharmaceutically acceptable salt thereof, wherein the anti-inflammatory compound derived from the bat moth intestinal fungus has the structure shown in compound 1-3:

[0008] The present invention also provides a method for preparing the above compound, which is prepared and separated from the fermentation product of the bat moth intestinal fungus Penicilium commune GIZ45-A73.

[0009] The specific steps include:

[0010] (1) Penicilium commune GIZ45-A73 is inoculated into a fermentation medium and cultured at 25-30° C. to obtain a fermentation product. The fermentation medium is prepared by adding 100 ml of water to every 100 g of rice;

[0011] (2) extracting the fermentation product obtained in step (1) with ethyl acetate, filtering to obtain an extract, and recovering the solvent from the extract under reduced pressure to obtain an extract;

[0012] (3) The extract obtained in step (2) was subjected to silica gel column chromatography, and the eluent was composed of petroleum ether-ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate was 50:1, 25:1, 10:1, 5:1, 2:1, and 1:1 in sequence for gradient elution; PC-c eluted with petroleum ether-ethyl acetate 10:1 was purified by silica gel column chromatography, and eluted with a mixed solvent of petroleum ether-ethyl acetate as an eluent, and the elution gradient was 25:1, 15:1, 10:1, 5:1, 3:1, 2:1, and 1:1 v / v, respectively, wherein the gradient elution was 3:1. The components obtained by elution were separated and purified by a preparative liquid chromatography system to obtain compound 1; the components obtained by gradient elution at 2:1 were separated and purified by a semi-preparative liquid chromatography system to obtain compound 2; PC-d eluted with petroleum ether-ethyl acetate 5:1 was purified by silica gel column chromatography using a mixed solvent of petroleum ether-ethyl acetate as an eluent, with elution gradients of 25:1, 15:1, 10:1, 5:1, 3:1, 2:1, and 1:1, respectively. The eluents with gradients of 5:1 and 3:1 were combined and separated and purified by a semi-preparative liquid chromatography system to obtain compound 3.

[0013] The fermentation product obtained in step (1) is extracted with ethyl acetate, the extraction conditions are as follows: the mass volume ratio of culture medium to ethyl acetate is 1:3, ultrasonic extraction is performed for 15 minutes, the number of extractions is 3 times, the power used for ultrasonic extraction is 400W, and the operating frequency is 40KHz.

[0014] The present invention also provides the use of the above-mentioned compound, or a pharmaceutically acceptable salt thereof, or a solvate thereof in the preparation of an anti-inflammatory drug, in particular a drug for treating chronic obstructive pulmonary disease.

[0015] The present invention also provides a medicine, which is a preparation prepared by using the above-mentioned compound, or a pharmaceutically acceptable salt thereof, or a solvate thereof as an active ingredient, and adding pharmaceutically acceptable excipients or auxiliary ingredients.

[0016] Beneficial effects of the present invention:

[0017] (1) The present invention is the first to obtain compounds 1-3 with anti-inflammatory activity from the metabolites of Penicilium commune GIZ45-A73. The metabolites of Penicilium commune GIZ45-A73 obtained from the intestine of the bat moth in the present invention are significantly different from the metabolites of Penicilium commune from other sources and are an important resource for discovering active metabolites.

[0018] (2) The bat moth intestinal fungus Penicilium commune GIZ45-A73 of the present invention can be fermented stably and in large quantities to produce compounds 1-3 with low cytotoxicity and significant anti-inflammatory activity.

[0019] (3) The compound of the present invention is produced by solid-state fermentation of Penicilium commune GIZ45-A73 fungus, which is derived from the intestine of bat moths. The compound can be obtained by extracting the fermentation product with ethyl acetate and then separating and purifying it using silica gel column chromatography and preparative liquid chromatography systems. The separation steps are simple, easy to implement, and easy to industrialize and mass produce, and has broad application prospects.

[0020] Deposit of biological materials:

[0021] Penicilium commune GIZ45-A73 was deposited in Guangdong Microbial Culture Collection (GDMCC) on March 18, 2024, at Institute of Microbiology, Guangdong Academy of Sciences, Guangdong, China, Postal Code: 510070, with the deposit number GDMCC NO: 64414. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] FIG1 is a 1H NMR spectrum of the compound having the structure of Formula 1 of the present invention.

[0023] FIG2 is a 13C NMR spectrum of the compound having the structure of Formula 1 of the present invention.

[0024] FIG3 is a 1H NMR spectrum of the compound having the structure of Formula 2 according to the present invention.

[0025] FIG4 is a 13C NMR spectrum of the compound having the structure of Formula 2 according to the present invention.

[0026] FIG5 is a 1H NMR spectrum of the compound having the structure of Formula 3 according to the present invention.

[0027] FIG6 is a 13C NMR spectrum of the compound having the structure of Formula 3 according to the present invention.

[0028] FIG7 shows the cell growth rate at different concentrations of the compound having the structure of Formula 1-3 of the present invention.

[0029] FIG8 is the result of IL-6 content determination of the anti-inflammatory activity of the compound having the structure of Formula 1-3 of the present invention. Specific implementation method:

[0030] Obviously, based on the above contents of the present invention, according to common technical knowledge and customary means in this field, without departing from the above basic technical ideas of the present invention, other various forms of modifications, replacements or changes can be made.

[0031] The following further describes the above content of the present invention in detail through specific embodiments in the form of examples. However, this should not be construed as limiting the scope of the above subject matter of the present invention to the following examples. All technologies implemented based on the above content of the present invention fall within the scope of the present invention.

[0032] The raw materials and equipment used in the present invention are all known products and are obtained by purchasing commercially available products.

[0033] Penicilium commune GIZ45-A73 was deposited in the Guangdong Microbial Culture Collection (GDMCC) on March 18, 2024, at the Institute of Microbiology, Guangdong Academy of Sciences, Guangdong, China, Postal Code: 510070, with the deposit number GDMCC NO: 64414.

[0034] Example 1. Preparation of the compound of the present invention

[0035] 1. Fermentation of bacteria

[0036] 1. Inoculate Penicilium commune GIZ45-A73 onto PDA medium and culture in the dark at 28°C for 7 days to obtain slant seeds.

[0037] 2. Transfer the slant seeds obtained in step 1 to liquid seed culture medium and culture in the dark at 28°C and 150 rpm for 4 days to obtain seed culture solution.

[0038] Liquid seed culture medium: The solvent is potato juice (potato juice preparation method: 200g potatoes, add about 1L of water, boil for 30min, filter, and make up the filtrate to 1L), the solute and its content are as follows: glucose 20g / L, agar 20g, high pressure sterilization (120℃, 20min).

[0039] 3. Inoculate about 10 mL of seed culture solution into a triangular flask containing fermentation medium, and culture at a constant temperature of 25°C for 30 days to obtain a fermentation product.

[0040] 4. Preparation of fermentation medium: Take 100g of rice, add 100ml of water, put it into a 500mL Erlenmeyer flask, and sterilize it under high pressure (120℃, 20min).

[0041] 2. Extraction, separation and purification of the compounds of the present invention

[0042] 1. Add 300 ml of ethyl acetate to the fermented flask containing the fermentation product, perform ultrasonic extraction at 30°C for 15 min, extract three times, with an ultrasonic power of 400 W and an operating frequency of 40 kHz, filter the extract, combine all the extracts and concentrate under reduced pressure at 40°C to obtain a total extract.

[0043] 2. The total extract and silica gel were stirred and evenly mixed in a mass ratio of 1:1, and then dry-loaded and subjected to silica gel column chromatography (the filler used in the silica gel column chromatography was 200-300 mesh column chromatography silica gel) with a mixed solution of petroleum ether and ethyl acetate (volume ratios of 50:1, 25:1, 10:1, 5:1, 2:1, and 1:1, respectively) as the eluent to obtain eight fractions, namely PC-a to PC-h.

[0044] 3. The PC-c (petroleum ether-ethyl acetate 10:1 elution portion) portion was purified again by silica gel column chromatography using a mixed solvent of petroleum ether-ethyl acetate as the eluent. The elution gradients were 25:1, 15:1, 10:1, 5:1, 3:1, 2:1, and 1:1 (v / v), respectively. Each gradient was eluted for 5 column volumes. The components eluted by gradient 3:1 were separated and purified by a preparative liquid chromatography system. The chromatographic column was filled with C18 (250*10mm, 5μm), the mobile phase was 80% methanol / water by volume, the flow rate was 1ml / min, and the chromatographic peak with a retention time of 30.5min was compound 1. The components eluted by gradient 2:1 were separated and purified by a preparative liquid chromatography system. The chromatographic column was filled with C18 (250*10mm, 5μm), the mobile phase was 70% methanol / water by volume, the flow rate was 1ml / min, and the chromatographic peak with a retention time of 27.5min was compound 2.

[0045] 4. The PC-d (petroleum ether-ethyl acetate 5:1 elution portion) was purified again by silica gel column chromatography using a mixed solvent of petroleum ether-ethyl acetate as the eluent. The elution gradients were 25:1, 15:1, 10:1, 5:1, 3:1, 2:1, and 1:1 v / v, respectively. Each gradient elution lasted 5 column volumes. The eluents of the 5:1 and 3:1 gradients were combined and separated and purified by a preparative liquid chromatography system. The chromatographic column was filled with C18 (250*10mm, 5μm), the mobile phase was 60% methanol / water by volume, the flow rate was 1ml / min, and the chromatographic peak with a retention time of 20.6min was compound 3.

[0046] 5. The NMR data of the above three compounds are as follows:

[0047] Compound 1: 1 H NMR (400 MHz, CDCl3) δ H :1.53(m,1H,9-H),1.63(s,3H,15-H),1.74(s,3H,14-H),1.73(m,1H,9-H),1.7 6(m,1H,5-H),2.07(m,1H,4-H),2.15(m,1H,1-H),2.18(m,1H,5-H),2.29(m,1H ,1-H),2.3-2.4(m,3H,4-H,6-H,8-H),2.42(m,1H,8-H),3.52(dd,J1=8.4Hz,J2=1.6Hz,1H,13-H),3.96(d,J=8.4Hz,1H,13-H),4.32(d,J=8.8Hz,1H,2-H), see Figure 1.

[0048] 13 C NMR (125 MHz, CDCl3) δ C :21.0(q,C-14),23.4(q,C-15),23.7(t,C-8),32.3(t,C-4),33.8(t,C-9),36.3(t,C-1),37.2(t,C-5),53.1(s,C-7 ),55.5(d,C-6),75.3(s,C-3),76.4(t,C-13),82.7(d,C-2),125.4(s,C-11),134.5(s,C-10),178.1(s,C-12), see Figure 2.

[0049] The molecular formula is C 15 H 22 O4, the structure is as follows:

[0050] Compound 2: 1 H NMR (600 MHz, DMSO-d6) δ H :7.07(2H,m,H-6,7),7.34(4H,m,H-8,9,12,16),7.44(1H,dt,J1=7.8Hz,H-14),J2=1.2Hz,7.52(2H,t,J=7.8Hz,H-13,15),9.22(1H,s,3-OH),12.24(1H,s,1-NH), see Figure 3.

[0051] 13 C NMR (150 MHz, DMSO-d6) δC :115.7(t,C-9),121.4(s,C-5),122.6(d,C-7),124.4(s,C-4),124.8(d,C-6),126.9(d,C-8),128.1(d,C-14),128.8(d,C-13,C-15),130.3(d,C-12,C-16),133.6(s,C-3),134.2(s,C-11),142.9(s,C-10),158.7(s,C-2), see Fig. 4, see Fig. 4.

[0052] The molecular formula is C 15 H 11 NO2, the structure is as follows:

[0053] Compound 3: 1 H NMR (500 MHz, CDCl3) δ H :2.04(1H,m,H-1),1.74(1H,m,H-1),2.56(1H,m, H-2),2.60(1H,m,H-2),1.65(1H,m,H-5),1.96(1H,m,H-5),2.17(1H,m,H-6),1.92(1H,m,H-6),2.44(1H,m,H-12),2.29(1H,m,1H) ,2.46(1H,m,1H),1.16(3H,s,H-12a),7.73(2H,d,J=9.0Hz,H-2',6'),6.93(2H,d,J=9.0Hz,H-3',5'),3.85(3H,s,4'-OCH3), see Figure 5.

[0054] 13 C NMR (125 MHz, CDCl3) δ C:32.7(t,C-1),33.6(t,C-2),215.5(s,C-3),52.9(s,C-4),21.4(q,4α-CH3),23.4(q,4β-CH3),79.1(s, C-4a),25.8(t,C-5),33.5(t,C-6),79.8(s,C-6a),20.4(q,6a-CH3),163.5(s,C-7a),96.7(d,C-8),158 .4(s,C-9),164.6(s,C-11),98.4(s,11a),17.2(t,C-12),43.5(d,C-12a),40.7(s,C-12b),18.6(q,12b-CH3),124.0(s,C-1'),127.0(d,C-2',6'),114.2(d,C-3',5'),161.5(s,C-4'),55.4(q,4'-OCH3), see Figure 6.

[0055] The molecular formula is C 17 H 16 N2O2, the structure is as follows:

[0056] The following experimental examples demonstrate the beneficial effects of the compounds of the present invention.

[0057] Example 2: Identification of the endophytic fungus Penicilium commune GIZ45-A73 of the present invention

[0058] Penicilium commune GIZ45-A73 was isolated from the intestine of a bat moth. It was identified by the Institute of Microbiology, Guangdong Academy of Sciences and stored in a refrigerator on a PDA slant at 4°C. Penicilium commune GIZ45-A73 was deposited with the Guangdong Provincial Microbiological Culture Collection (GDMCC) on March 18, 2024, at the Institute of Microbiology, Guangdong Academy of Sciences, Guangdong, China, with the deposit number GDMCC NO: 64414.

[0059] Based on the DNA sequence of the internal transcribed spacer (ITS), the fungal strain was identified as Penicilium commune by NCBI BLAST analysis. The following sequence was used in the BLAST search. SEQ ID NO. 1:

[0060] Example 3: Anti-inflammatory activity test of the compounds of the present invention

[0061] Interleukin-6 (IL-6) is an important inflammatory factor, and increased IL-6 expression promotes the development of inflammation. Studies have found that not only are IL-6 levels elevated in the blood, sputum, and bronchoalveolar lavage fluid of patients with inflammation, but their soluble IL-6 receptors are also increased. Therefore, IL-6 can be used as an indicator of the development of inflammation. Chronic obstructive pulmonary disease (COPD) is a disease associated with long-term chronic inflammatory stimulation. This inflammatory stimulation can lead to overexpression of inflammatory factors and changes in immune function. During acute attacks, multiple inflammatory factors are continuously released in large quantities, causing severe worsening of the disease and subsequently affecting the overall treatment effect (Gao J, Wu S, Lin W, et al. Blood cells for the differentiation of AECOPD airway inflammatory phenotypes[J]. Basic clin pharmacol toxicol. 2019, 125(SI):57-58.). Therefore, IL-6 can be used as an inflammatory indicator substance and may also be a potential target for the treatment of diseases such as COPD (Winslow S, Odqvist L, Diver S, et al. Multi-omics links IL-6 trans-signalling with neutrophil extracellular trap formation and Haemophilus infection in COPD[J]. Eur Respir J. 2021, 58(4): 1-14.). The present invention evaluates the anti-inflammatory activity of compound 1-3 by acting on lipopolysaccharide (LPS)-induced human bronchial epithelial cells Beas2b and detecting the IL-6 content produced in the cell culture supernatant.

[0062] 1. Reagents and Instruments

[0063] Human bronchial epithelial cells Beas-2b; lipopolysaccharide (LPS); DMEM high-glucose medium; fetal bovine serum (FBS); phosphate-buffered saline (PBS); dimethyl sulfoxide (DMSO); 1% P / S double-antibody; enzyme-linked immunosorbent assay kit (ELISA kit); precision electronic balance; biological safety cabinet; carbon dioxide incubator; inverted microscope; low-speed refrigerated centrifuge; microplate reader; digital constant-temperature water bath.

[0064] 2. Culture of Beas-2b cells

[0065] The basal culture medium is DMEM culture medium + 10% FBS + 1% P / S double antibody; the culture conditions are 37°C, 5% CO2 and saturated humidity; after culturing for 2 to 3 days, the cell density reaches 90% and can be used for experiments.

[0066] 3. Cell Viability Assay

[0067] Beas-2b cells in the logarithmic growth phase were taken and prepared into 2×10 5 A single-cell suspension of 100 μl / well was seeded into a 96-well plate (3 replicates per group). After the cells adhered, they were cultured until the confluence was approximately 80%. The original culture medium was discarded, and normal culture medium (1 μl of compound solvent and 99 μl of DMEM medium) was added to the control group. Culture medium containing different concentrations of compounds (1 μl of compound solution and 99 μl of DMEM medium) was added to the sample group. The culture was continued for 24 hours. The cell growth status and culture medium changes were observed under an inverted microscope. After the culture was completed, 10 μl of CCK-8 working solution was added to each well, incubated at 37°C for 2 hours, and detected at 450 nm.

[0068] Cell growth rate = (drug-added well - background value) / (control well - background value) × 100%

[0069] The experimental results are shown in Figure 7: Compound 1 had no significant inhibitory effect on Beas2b cells at a concentration below 100 μM, indicating that compound 1 has very little toxicity to Beas2b cells; Compound 2 had no significant inhibitory effect on Beas2b cells at a concentration below 5 μM, indicating that compound 2 has very little toxicity to Beas2b cells within this concentration range; Compound 3 had no significant inhibitory effect on Beas2b cells at a concentration below 10 μM, indicating that compound 3 has very little toxicity to Beas2b cells within this concentration range.

[0070] 4. Determination of anti-inflammatory activity of compounds 1-3

[0071] Beas-2b cells in the logarithmic growth phase were taken and the cell density was adjusted to 2×10 6Cells were seeded into a 48-well plate at a volume of 500 μl / well. After the cells adhered, they were cultured until the confluence reached about 80%. The culture medium was discarded, and a control group, a model group, and a sample group were set up. The control group did not add LPS and sample. The model group added LPS solution to the culture medium (the final concentration of LPS was 1 μg / ml). The sample group added fresh DMEM culture medium containing LPS and sample solution (the final concentration of compound 1-3 was 5 μM). The culture was continued for 24 hours. After the culture was completed, the supernatant of each well was collected into a 1.5 ml centrifuge tube and centrifuged at 6000 rpm for 5 minutes. The supernatant was transferred to another 1.5 ml centrifuge tube and stored at -20°C for ELISA detection. The IL-6 content was detected according to the instructions of the ELISA kit.

[0072] The experimental data were expressed as mean ± standard deviation (x ± s), and the inter-group comparison was performed using SPSS 22.0 statistical software for single-factor analysis of variance to analyze the significant differences. * p<0.05, ** p<0.01 indicates a significant difference, which is statistically significant; comparison between the sample group and the model group # p<0.05, ## p<0.01 indicates a significant difference and is statistically significant.

[0073] As shown in Figure 8, the IL-6 content in the model group was significantly different from that in the control group, indicating that the model was successfully established. The IL-6 content in the sample group was significantly lower than that in the model group, indicating that compound 1-3 has the ability to inhibit IL-6 expression activity, thereby exerting an anti-inflammatory effect.

[0074] Chronic obstructive pulmonary disease (COPD) is a chronic disease closely related to inflammation. Inhibiting the progression of inflammation is an important method and approach for treating COPD. Compounds 1-3 of the present invention have significant anti-inflammatory activity at concentrations as low as 5 μM. Therefore, compounds 1-3 of the present invention have the potential to be developed into anti-inflammatory drugs for the treatment of COPD and other diseases.

Claims

1. Any compound of formula I or a pharmaceutically acceptable salt thereof, the structure of the compound is as follows: 2.Penicilium commune GIZ45-A73, deposit number is GDMCC NO:64414.

3. A method for preparing the compound according to claim 1, characterized in that: It is prepared and separated from the fermentation product of Penicilium commune GIZ45-A73 described in claim 2.

4. The preparation method according to claim 3, characterized in that: The steps include: (1) Penicilium commune GIZ45-A73 is inoculated into a fermentation medium and cultured at 25-30° C. to obtain a fermentation product. The fermentation medium is prepared by adding 100 ml of water to every 100 g of rice; (2) extracting the fermentation product obtained in step (1) with ethyl acetate, filtering to obtain an extract, and reducing the pressure of the extract to recover the solvent to obtain an extract; (3) The extract obtained in step (2) was subjected to silica gel column chromatography, and gradient elution was performed in a volume ratio of 50:1, 25:1, 10:1, 5:1, 2:1, and 1:1 with an eluent consisting of petroleum ether and ethyl acetate; PC-c eluted with a petroleum ether-ethyl acetate ratio of 10:1 was purified by silica gel column chromatography, and eluted with a mixed solvent of petroleum ether-ethyl acetate as an eluent, and the elution gradient was 25:1, 15:1, 10:1, 5:1, 3:1, 2:1, and 1:1 v / v, respectively; the components obtained by the gradient 3:1 elution were separated and purified by a preparative liquid chromatography system to obtain compound 1; the components obtained by the gradient 2:1 elution were separated and purified by a semi-preparative liquid chromatography system to obtain compound 1. The system was separated and purified to obtain compound 2; PC-d eluted with petroleum ether-ethyl acetate 5:1 was purified by silica gel column chromatography using a mixed solvent of petroleum ether-ethyl acetate as eluent, and the elution gradients were 25:1, 15:1, 10:1, 5:1, 3:1, 2:1, and 1:1, respectively; the eluents with gradients of 5:1 and 3:1 were combined and separated and purified by semi-preparative liquid chromatography system to obtain compound 3.

5. The preparation method according to claim 4, characterized in that: The fermentation product obtained in step (1) is extracted with ethyl acetate, the extraction conditions are that the mass volume ratio of the culture medium to the ethyl acetate is 1:3, the ultrasonic extraction is performed for 15 minutes, the number of extractions is 3 times, the power used for the ultrasonic extraction is 400W, and the operating frequency is 40KHz.

6. Use of the compound according to claim 1, or a pharmaceutically acceptable salt thereof, or a solvate thereof in the preparation of an anti-inflammatory drug.

7. The use according to claim 6, characterized in that: The anti-inflammatory drug is a drug for treating chronic obstructive pulmonary disease.

8. An anti-inflammatory drug, characterized in that: The invention relates to a preparation prepared by taking the compound described in claim 1, or a pharmaceutically acceptable salt thereof, or a solvate thereof as an active ingredient, and adding pharmaceutically acceptable excipients or auxiliary ingredients.

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