Star polymer for promoting lung function repair and preparation method thereof

Abstract

The application provides a star-shaped polymer for promoting lung function repair and a preparation method thereof. On the basis of a hydroxyl chalcone, epoxy modification is performed to obtain an epoxidized chalcone, the introduced epoxy group is used to graft the epoxidized chalcone to amino groups on side arms of a star-shaped copolymer mother nucleus, and polyethylene glycol segments are grafted on the side arms of the star-shaped copolymer mother nucleus to increase water solubility, thereby improving the defects that the chalcone compound has a high melting point and is difficult to dissolve in water. In addition, the core of the star-shaped copolymer contains a cystamine structure, and the core is easy to undergo a reduction reaction in a living body, thereby promoting the degradation and absorption of the star-shaped polymer in the living body, and finally improving the anti-inflammatory activity of the star-shaped polymer and the effect of promoting lung function repair.

Description

Technical Field

[0001] This invention belongs to the field of medicinal chemistry technology, specifically relating to an epoxidized chalcone compound and its preparation method, as well as the corresponding star polymer and its preparation method and application. Background Technology

[0002] Many diseases, such as rheumatoid arthritis and lung injury, are related to inflammation. Inflammation is a defensive response of the body to damage and harmful stimuli, but excessive inflammation can cause secondary tissue damage and dysfunction. The inflammatory process is associated with the overexpression of pro-inflammatory factors and oxidative stress, which further exacerbates the inflammatory response. Currently, anti-inflammatory therapy is considered an effective treatment for inflammatory diseases, but conventional clinical anti-inflammatory treatments usually include antibiotics and systemic steroids. These treatments are singular, focusing only on preventing bacterial infection and failing to directly cure the inflammation. Furthermore, most antibiotics have side effects, including cardiovascular disease and liver and kidney toxicity. Therefore, developing new and effective inflammation control strategies is crucial.

[0003] Compared to traditional treatments, a promising new approach is to synthesize bioactive polymers and use them as substances to modulate the inflammatory environment. Various polymer-based nanoparticles and nanovesicles have been developed and have played a positive role in anti-inflammatory therapy. For example, the literature doi:10.1021 / acsnano.8b01152; doi:10.1002 / adfm.201501712; doi:S2452199X20302176 developed poly(citrate-silicon), polycitrate-polyethyleneimine, and polycitrate-based bone nanocomposites. Functionalization is achieved through chemical grafting or reaction of citrate with polymers, thereby activating mitochondria to effectively stimulate cell proliferation and modulating the inflammatory response through their antioxidant capacity.

[0004] However, most reported polymers suffer from low bioactivity, poor durability, and complex synthesis. Therefore, developing novel bioactive polymer nanosystems with simple synthesis, strong anti-inflammatory activity, and good biocompatibility remains essential for treating inflammatory diseases. Furthermore, from the perspective of better developing polymers that regulate the inflammatory environment and improving degradation controllability, using natural bioactive molecules as monomers to synthesize polymers with controllable activity is also a current novel strategy.

[0005] Numerous bioactive natural small molecules exist, such as polyphenols, flavonoids, paclitaxel, and camptothecin. Flavonoids, in particular, are a class of secondary metabolites widely distributed in higher plants, with the general molecular formula being a series of C6Ar-C3-C6Ar compounds consisting of two benzene rings linked by three carbon atoms. Current research has identified various flavonoids with diverse biological functions, including anticancer, antioxidant, anti-inflammatory, antibacterial, antiviral, neurite growth stimulating, and cardiovascular disease prevention effects. Due to their diverse structures, flavonoids can bind to different receptors, exhibiting broad target effects, significant biological activity, and low toxicity, making them ideal molecular templates. However, the molecular structure of flavonoids results in high melting points (at least above 50°C) and poor water solubility, limiting their direct medicinal use due to low solubility, absorption rate, and bioavailability. Summary of the Invention

[0006] The purpose of this invention is to overcome the above shortcomings and to propose an epoxidized chalcone compound and its preparation method, as well as the corresponding star polymer and its preparation method and application.

[0007] To achieve the above-mentioned technical objectives, the technical solution adopted by the present invention is as follows:

[0008] Firstly, an epoxidized chalcone compound has the following structure:

[0009]

[0010] Preferably, the structure of the epoxidized chalcone compound includes:

[0011] or

[0012] Secondly, the preparation method of the above-mentioned epoxidized chalcone compound includes: reacting hydroxychalcone with epichlorohydrin to obtain it;

[0013] Furthermore, the molar ratio of hydroxychalcone to epichlorohydrin is 1:(1-2);

[0014] Furthermore, a quaternary ammonium salt is used as a catalyst in the reaction of hydroxychalcone with epichlorohydrin; preferably, the quaternary ammonium salt is benzyltriethylammonium chloride;

[0015] Preferably, the amount of catalyst used is 0.5-5 wt% of the total weight of the reactants;

[0016] Preferably, the hydroxychalcone is selected from any one or both of 2'-hydroxychalcone and 4'-hydroxychalcone;

[0017] Furthermore, the specific steps of the preparation method include:

[0018] S1. The reactant hydroxychalcone is mixed evenly with epichlorohydrin and quaternary ammonium salt catalyst and then reacted.

[0019] S2. Add an aqueous solution of NaOH dropwise to the reaction system;

[0020] S3. After the reaction is complete, the crude product is filtered and extracted separately. The organic phase is dried and distilled under reduced pressure to obtain the epoxidized chalcone compound.

[0021] Preferably, the reaction temperature in step S1 is 80-120℃, and the reaction time is 1-4 hours;

[0022] Preferably, the concentration of the NaOH aqueous solution in step S2 is 20-50 wt%.

[0023] Preferably, the reaction temperature in step S2 is 80-120℃, and the reaction time is 1-4 hours;

[0024] Preferably, nitrogen or an inert gas is continuously introduced into the reaction system in steps S1 and S2 for protection.

[0025] Preferably, in step S3, the product after vacuum distillation is further dried under vacuum at a temperature of room temperature to 60°C.

[0026] Thirdly, a star-shaped polymer includes a cystamine core and linear side arms, wherein the linear side arms are sequentially connected to the cystamine core, and the number of linear side arms per molecule is ≥4.

[0027] The linear side arms include: ungrafted linear side arms, linear side arms grafted with polyethylene glycol segments, and linear side arms grafted with chalcone.

[0028] The chemical structure of the cystamine core is as follows:

[0029] The chemical structures of ungrafted linear side arms include: or Any one or both of them;

[0030] The chemical structure of the linear side arm of the grafted polyethylene glycol segment is as follows: Where n≥1;

[0031] The linear side arms of grafted chalcone have the following chemical structures: or Any one or both of them;

[0032] Fourthly, the method for preparing the star polymer described above includes: grafting polyethylene glycol segments and epoxidized chalcone compounds onto the linear side arms of the star polymer core;

[0033] Among them, the star polymer core is selected from: G0 generation, G1 generation or G2 generation PAMAM star polymer with cystamine as the core;

[0034] Methods for grafting polyethylene glycol segments onto linear side arms of a star polymer core include: reacting methoxycarboxylated polyethylene glycol with amino groups of the linear side arms of the star polymer core;

[0035] Preferably, 2-(7-azabenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate (HATU) is used as a catalyst in the reaction process;

[0036] Preferably, the reaction process is carried out at a temperature of room temperature to 60°C;

[0037] Preferably, the molar ratio of the carboxyl group in the methoxycarboxylated polyethylene glycol to the amino group in the star polymer core is (1-2):4;

[0038] The method of grafting epoxidized chalcone compounds onto the linear side arms of a star polymer core also includes: reacting the epoxidized chalcone compound with an amino group on the linear side arm of the star polymer core;

[0039] Preferably, the reaction process is carried out at a temperature of room temperature to 60°C;

[0040] Preferably, the molar ratio of the epoxy group in the epoxidized chalcone compound to the amino group in the star polymer core is (0.5-2):1;

[0041] Even more preferably, the molar ratio of the epoxy group in the epoxidized chalcone compound to the amino group in the star polymer core is (0.5-1.5):1.

[0042] Fifthly, the application of the above-mentioned epoxidized chalcone compounds and / or star polymers in the preparation of drugs that promote lung function repair.

[0043] The beneficial effects of this invention are as follows: Hydroxychalcone is modified with epoxy groups to obtain epoxidized chalcone compounds. The introduced epoxy groups are then grafted onto the amino groups of the side arms of the star copolymer core. Simultaneously, polyethylene glycol segments are grafted onto the side arms of the star copolymer core to increase the water solubility of the star copolymer, thereby improving the absorption rate and utilization of the chalcone-terminated star copolymer in vivo. Furthermore, the core of the star copolymer contains a cystamine structure, which readily undergoes a reduction reaction in vivo, thereby promoting the degradation and absorption of the star polymer in vivo. This enhances the anti-inflammatory activity of the star polymer and promotes lung function repair. Such chalcone-terminated star copolymers have application value in the pharmaceutical field. Attached Figure Description

[0044] Figure 1 The effects of the star-shaped polymers or mixtures prepared in Examples 2-4 and Comparative Example 1 on the proliferation capacity of BEAS-2B cells.

[0045] Figure 2 The results of the scratch assay on BEAS-2B cells are as follows: The star-shaped polymers or mixtures prepared in Examples 2-4 and Comparative Example 1.

[0046] Figure 3 The effects of the star-shaped polymers or mixtures prepared in Examples 2-4 and Comparative Example 1 on the migration ability of BEAS-2B cells.

[0047] Figure 4 The effect of the star-shaped polymers or mixtures prepared in Examples 2-4 and Comparative Example 1 on the transepithelial resistance of BEAS-2B cells. Detailed Implementation

[0048] The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the protection scope of the present invention. It should be noted that the terminology used herein is only for describing specific implementations and is not intended to limit the exemplary implementations of the present invention. As used herein, unless the context clearly indicates otherwise, the singular form is intended to include the plural form as well. Furthermore, it should be understood that when the terms "comprising" and / or "including" are used in this specification, they indicate the presence of features, steps, operations, devices, components, and / or combinations thereof.

[0049] Unless otherwise specified, experimental conditions not described in the examples shall be performed according to conventional conditions in the art or as recommended by the reagent company. Unless otherwise specified, all materials and reagents used in the examples are commercially available.

[0050] Example 1

[0051] Epoxidation of 4'-hydroxychalcone: In a three-necked flask equipped with a stirrer, reflux condenser, and nitrogen purging device, 89.7 g of 4'-hydroxychalcone, 5.0 g of benzyltriethylammonium chloride, and 55.5 g of epichlorohydrin were added sequentially. Under continuous nitrogen purging, the flask was heated to 100 °C and reacted for 3 h. Subsequently, 40 mL of a 40% (w / w) NaOH aqueous solution was added dropwise to the system, and the reaction was continued at 100 °C for 1 h. After the reaction was completed, the mixture was filtered, and the filtrate was extracted with distilled water. The mixture was separated into three layers, and the organic layer was dried with anhydrous sodium sulfate. The mixture was then filtered again, and the solvent was removed by vacuum distillation. The product was dried in a vacuum oven at 50 °C to obtain 4'-hydroxychalcone glycidyl ether in 89% yield.

[0052] The reaction formula for the preparation of 4'-hydroxychalcone glycidyl ether in Example 1 is as follows:

[0053]

[0054] The structure of the product 4'-hydroxychalcone glycidyl ether was confirmed as follows:

[0055] 1H NMR spectrum 1 H NMR (CDCl3, 400MHz): δ2.89-3.17(3H,2.95(dd,J=8.06,4.18Hz), 3.06(dd,J=7.68,4.18Hz), 3.08(dddd,J=8. 06,7.68,5.14,5.14Hz)),4.56-4.67(2H,4.61(d,J=5.14Hz),4.61(d,J=5.14Hz)),6.72(1H,d,J=15.68Hz),7 .07(2H,ddd,J=8.30,1.23,0.46Hz),7.36-7.64(8H,7.43(dddd,J=7.90,7.23,1.99,0.46Hz),7.44(tt,J=7.2 3, 1.31Hz), 7.45 (dddd, J = 7.90, 1.60, 1.31, 0.46Hz), 7.51 (d, J = 15.68Hz), 7.58 (dddd, J = 8.30, 1.81, 0.46Hz)).

[0056] Carbon NMR Spectroscopy 13C NMR(CDCl3,100MHz): δ44.64(1C,s),50.35(1C,s),69.51(1C,s),114.34(2C,s),121.17(1C,s),128.02(1C,s),128.0 7(2C,s),128.31(2C,s),130.65(2C,s),134.22(1C,s),134.90(1C,s),144.66(1C,s),156.48(1C,s),188.36(1C,s).

[0057] Example 2

[0058] Polyethylene glycol-grafted star polymer: Weigh the G1 generation PAMAM star polymer with cystamine core (Weihai Chenyuan, molecular formula C). 64 H 132 N 26 O 12 7.61 g of S2) was added to a three-necked flask, along with 12.5 g of 1000 molecular weight methoxycarboxylated polyethylene glycol, 0.1 g of catalyst 2-(7-azabenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate (HATU), and 0.5 mL of triethylamine. The mixture was reacted at 40 °C for 2 hours. The solvent was removed by vacuum distillation to obtain the star-shaped polymer grafted with polyethylene glycol.

[0059] Synthesis of chalcone-terminated star polymer: 5.61 g of 4'-hydroxychalcone glycidyl ether was added at 40 °C, and 5 mL of ethyl acetate was used as solvent. The mixture was stirred at 40 °C for 1 hour. After the reaction was completed, the solvent was removed by vacuum distillation to obtain the chalcone-terminated star polymer.

[0060] Example 3

[0061] Polyethylene glycol grafted star polymer: Same as in Example 2.

[0062] Synthesis of chalcone-terminated star polymer: 11.21 g of 4'-hydroxychalcone glycidyl ether was added at 40 °C, and 10 mL of ethyl acetate was used as solvent. The mixture was stirred at 40 °C for 1 hour. After the reaction was completed, the solvent was removed by vacuum distillation to obtain the chalcone-terminated star polymer.

[0063] Example 4

[0064] Polyethylene glycol grafted star polymer: Same as in Example 2.

[0065] Synthesis of chalcone-terminated star polymer: 16.82 g of 4'-hydroxychalcone glycidyl ether was added at 40 °C, and 15 mL of ethyl acetate was used as solvent. The mixture was stirred at 40 °C for 1 hour. After the reaction was completed, the solvent was removed by vacuum distillation to obtain the chalcone-terminated star polymer.

[0066] Comparative Example 1

[0067] 16.82g of 4'-hydroxychalcone glycidyl ether, 7.61g of G1 generation PAMAM star polymer with cystamine core, and 12.5g of 1000 molecular weight methoxycarboxylated polyethylene glycol were physically blended under mechanical stirring for 30 minutes and set aside.

[0068] Comparative Example 2

[0069] Synthesis of chalcone-terminated star polymers: Same as in Example 4, but without using polyethylene glycol segments to graft the star polymers.

[0070] In vitro experiments

[0071] A cell injury model was constructed by treating human bronchial epithelial BEAS-2B cells with lipopolysaccharide (LPS). The human bronchial epithelial cells (BEAS-2B) were purchased from the China Center for Type Culture Collection (CCTCC).

[0072] The effects of the star polymers or mixtures prepared in Examples 2-4 and Comparative Example 1 on cell proliferation due to inflammatory damage were tested using 5-ethynyl-2'-deoxyuridine (EdU) staining. BEAS-2B cells were inoculated at 4 × 10⁻⁶ cells per cell line. 5 Cells were evenly seeded per well in 6-well plates and placed in an incubator. Cell treatment was divided into: blank group, control group, Example 2 group, Example 3 group, Example 4 group, and Comparative Example 1 group. Examples 2, 3, 4, and Comparative Example 1 groups used 10 μM chalcone-terminated star polymers or blends prepared with DMSO for pretreatment for 2 hours, followed by LPS treatment for 24 hours. 1 mL of paraformaldehyde was added to each well for fixation for 15 min, then the fixative was discarded. 1 mL of PBS buffer was added to each well for decolorization and rinsing twice on a shaker for 3 min each time. Finally, nuclear staining was performed. After staining, the slides were removed from the 6-well plates, and the cell surfaces were placed on slides containing anti-fluorescence quencher. The slides were then mounted and observed and photographed using a laser confocal microscope. The photographs were analyzed and quantitatively compared using ImageJ software. The test results are listed below. Figure 1 .

[0073] The effect of chalcone-capped star polymers on the migration ability of BEAS-2B cells was tested using a scratch assay. The specific procedure for the scratch assay involved drawing two vertical lines on the back of each well in a six-well plate using a marker pen. BEAS-2B cells in the logarithmic growth phase were then sputtered at a rate of 5 × 10⁶ cells / well. 5 Cells were inoculated into six-well plates and placed in a cell culture incubator overnight. Once the cell confluence reached 80%, a 200 μL pipette tip was used to replicate the cells along the drawn lines. Simultaneously, 10 μM chalcone-capped star polymers or blends prepared using DMSO (as in Examples 2, 3, 4, and Comparative Example 1) were added for pretreatment for 2 hours before incubation. LPS was then added, and images were taken under a microscope at 0, 12, and 24 hours. The images were analyzed and quantitatively compared using ImageJ software. The test results are listed below. Figure 2 , Figure 3 .

[0074] The effect of chalcone-terminated star polymers on lung epithelial cell barrier dysfunction was assessed by measuring transepithelial electric resistance (TEER) values. Specifically, BEAS-2B cells were inoculated into Transwell chambers, and the cell resistance values ​​in the upper and lower chambers of the Transwell were read using a resistance meter. This reflects the integrity of the lung epithelial cell structure and the permeability and filtration of the cells. The test results are listed below. Figure 4 .

[0075] animal experiments

[0076] Sixty-four SPF-grade mice (Guangzhou Cyagen Biotechnology Co., Ltd.) were randomly divided into eight groups: a blank control group, an LPS model group, experimental groups (Examples 1-4), and control groups (Comparative Examples 1 and 2). Two hours before modeling, mice were administered 10 mg / kg of 4'-hydroxychalcone glycidyl ether from Example 1, chalcone-terminated star polymers from Examples 2, 3, and 4 and Comparative Example 2, and a mixture of 10 mg / kg from Comparative Example 1 via gavage, according to their respective groups. The mice were then nebulized with LPS for 30 minutes, with a total nebulization volume and concentration of 12 mL of 2.5 g / mL LPS. After nebulization, the mice were returned to their cages, and euthanized 48 hours later. Lung tissue samples and bronchoalveolar lavage fluid were collected for further testing.

[0077] The relevant tests in the animal experiments included: wet-to-dry weight ratio (W / D) of mouse lung tissue, extraction of mouse bronchoalveolar lavage fluid, collection of cell pellets from the lavage fluid, detection of the types and numbers of inflammatory cells in the lavage fluid using an animal blood analyzer, and detection of the level of the inflammatory factor TNF-α in mouse serum using a TNF-α ELISA kit. All test data are expressed as mean ± standard deviation. The test results are listed in Table 1.

[0078] Table 1

[0079]

[0080] go through Figure 1 EdU staining results showed that treating BEAS-2B cells with 20 μg / mL LPS for 24 h significantly reduced the number of EdU-labeled positive cells. However, under conditions of adding 4'-hydroxychalcone glycidyl ether from Example 1, chalcone-capped star polymers from Examples 2, 3, and 4 and Comparative Example 2, and a 10 mg / kg mixture of Comparative Example 1 at 10 μM, the number of EdU-labeled positive cells increased. Comparative analysis of the test results from Examples 2-4 revealed that as the amount of 4'-hydroxychalcone glycidyl ether used as the capping agent increased, the corresponding number of EdU-labeled positive cells also increased, indicating a dose-dependent relationship between 4'-hydroxychalcone glycidyl ether and cell proliferation rate. Comparative Example 1 did not use 4'-hydroxychalcone glycidyl ether to cap the star polymer, but directly physically mixed 4'-hydroxychalcone glycidyl ether with G1 generation PAMAM star polymer and methoxycarboxylated polyethylene glycol. Comparative Example 2 did not use polyoxyethylene segment grafted star polymer. The products prepared by Comparative Examples 1 and 2 still had the effect of increasing the proliferation rate of BEAS-2B cells, but compared with Example 4 with the same amount of chalcone compound, the effect of Comparative Examples 1 and 2 on increasing the proliferation rate of BEAS-2B cells was poor.

[0081] go through Figure 2 , 3 The scratch assay results showed that, compared with the control group, LPS significantly inhibited cell scratch wound healing and significantly reduced cell migration ability. However, under the conditions of adding 4'-hydroxychalcone glycidyl ether from Example 1, chalcone-terminated star polymers from Examples 2, 3, and 4 and Comparative Example 2, and a mixture of 10 mg / kg of Comparative Example 1 at 10 μM, the scratch wound healing of BEAS-2B cells was accelerated and the migration ability was significantly enhanced. Compared with Example 4 with the same amount of chalcone compound, the mixture of Comparative Example 1 and the star polymer of Comparative Example 2 without polyethylene glycol grafting had a lower effect on the improvement of BEAS-2B cell migration ability.

[0082] go through Figure 4Transepithelial electrical resistance (TER) tests revealed that after 24 hours of adding 20 μg / mL LPS, the TRR of BEAS-2B cells decreased by 25-30%. However, the addition of 4'-hydroxychalcone glycidyl ether from Example 1, chalcone-terminated star polymers from Examples 2, 3, and 4 and Comparative Example 2, and a mixture of 10 mg / kg from Comparative Example 1 at 10 μM significantly inhibited the LPS-induced decrease in BEAS-2B cell TRR, thus preventing damage to the lung epithelial cell barrier function. Compared to Example 4 with the same amount of chalcone-based compound, the mixture from Comparative Example 1 and the star polymer from Comparative Example 2 without polyethylene glycol grafting showed a decreased ability to maintain the BEAS-2B cell barrier function.

[0083] Analysis of the data in Table 1 shows that the wet / dry weight ratio (W / D) of lung tissue, as an indicator of the severity of pulmonary edema, significantly increased the W / D value in the LPS model group mice compared to the control group, indicating severe pulmonary edema. The use of 4'-hydroxychalcone glycidyl ether from Example 1, chalcone-terminated star polymers from Examples 2, 3, and 4, the mixture from Comparative Example 1, and the chalcone-terminated star polymer from Comparative Example 2 all reduced the W / D value in mice, indicating that the chalcone-terminated star polymer can improve pulmonary edema in mice. The 4'-hydroxychalcone glycidyl ether prepared in Example 1 showed relatively little effect on improving pulmonary edema in mice, possibly due to the poor hydrophilicity of the chalcone compound itself. Furthermore, compared to Example 4 with the same amount of chalcone compound, Comparative Example 1 (without end-capping) and Comparative Example 2 (without the introduction of polyethylene glycol segments) showed even worse effects on reducing the W / D value in mice.

[0084] The inflammation and pulmonary bronchodilator status of mice were assessed by analyzing the content of neutrophils, lymphocytes, and monocytes in inflammatory cells. The LPS model group showed a significant increase in the number of neutrophils, lymphocytes, and monocytes in inflammatory cells. The use of 4'-hydroxychalcone glycidyl ether from Example 1, chalcone-terminated star polymers from Examples 2, 3, and 4, a mixture from Comparative Example 1, and a chalcone-terminated star polymer from Comparative Example 2 reduced the number of these inflammatory cells in the experimental groups, improved pulmonary bronchial permeability, and alleviated inflammatory damage. The 4'-hydroxychalcone glycidyl ether prepared in Example 1 had a relatively weak effect on reducing the number of inflammatory cells in mice, possibly due to the poor hydrophilicity of the chalcone compound itself. Furthermore, compared to Example 4 with the same amount of chalcone compound, Comparative Example 1 (without end-capping) and Comparative Example 2 (without the introduction of polyethylene glycol segments) showed a worse reduction in inflammatory cells in mice.

[0085] The level of the inflammatory factor TNF-α in the serum of LSP model mice was detected by ELISA. It was found that the TNF-α level was approximately 1.7 times higher than that of the control group. However, the levels of TNF-α in the serum of mice using the 4'-hydroxychalcone glycidyl ether of Example 1, the chalcone-terminated star polymers of Examples 2, 3, and 4, the mixture of Comparative Example 1, and the chalcone-terminated star polymer of Comparative Example 2 were significantly lower, demonstrating anti-inflammatory activity. The 4'-hydroxychalcone glycidyl ether prepared in Example 1 had a relatively weak effect on reducing TNF-α levels in mouse serum, possibly due to the poor hydrophilicity of the chalcone compound itself. Furthermore, compared to Example 4 with the same amount of chalcone compound, Comparative Example 1 (without the end-capping reaction) and Comparative Example 2 (without the introduction of polyethylene glycol segments) showed even worse effects on reducing TNF-α levels in mouse serum.

[0086] Finally, it should be noted that the above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of them. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention. Although the specific embodiments of the present invention have been described above, they are not intended to limit the protection scope of the present invention. Those skilled in the art should understand that various modifications or variations that can be made by those skilled in the art without creative effort based on the technical solutions of the present invention are still within the protection scope of the present invention.

Claims

1. A star-shaped polymer, characterized in that, The star polymer consists of a cystamine core and linear side arms, with the linear side arms sequentially connected to the cystamine core, and the number of linear side arms per molecule is ≥4. The linear side arms include: ungrafted linear side arms, linear side arms grafted with polyethylene glycol segments, and linear side arms grafted with chalcone. The chemical structure of the cystamine core is as follows: ； The chemical structures of ungrafted linear side arms include: or Any one or both of them; The chemical structure of the linear side arm of the grafted polyethylene glycol segment is as follows: where n≥1; The linear side arms of grafted chalcone have the following chemical structures: or Any one or two of them.

2. The method for preparing the star-shaped polymer as described in claim 1, characterized in that, Polyethylene glycol segments and epoxidized chalcone compounds were grafted onto the linear side arms of a star polymer core. The star-shaped polymer core is selected from G0, G1 or G2 generation PAMAM star-shaped polymers with cystamine as the core.

3. The method for preparing the star-shaped polymer according to claim 2, characterized in that, Methods for grafting polyethylene glycol segments onto linear side arms of a star polymer core include: reacting methoxycarboxylated polyethylene glycol with amino groups of the linear side arms of the star polymer core; And / or, 2-(7-azabenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate (HATU) is used as a catalyst in the reaction process; And / or, the reaction process is carried out at a temperature ranging from room temperature to 60°C; And / or, the molar ratio of the carboxyl group in methoxycarboxylated polyethylene glycol to the amino group in the star polymer core is (1-2):

4.

4. The method for preparing the star-shaped polymer according to claim 2, characterized in that, A method for grafting an epoxidized chalcone compound onto a linear side arm of a star polymer core includes: reacting the epoxidized chalcone compound with an amino group on a linear side arm of the star polymer core; And / or, the reaction process is carried out at a temperature ranging from room temperature to 60°C; And / or, the molar ratio of the epoxy group in the epoxidized chalcone compound to the amino group in the star polymer core is (0.5-2):

1.

5. An application characterized in that, The use of the star-shaped polymer of claim 1 in the preparation of a drug that promotes lung function repair.

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