Antibacterial dendritic polyester macromolecule, and preparation method and application thereof

Abstract

The application discloses an antibacterial dendritic polyester macromolecule, a preparation method and application thereof, and belongs to the biomedical field. The amino is grafted on the branch of the dendritic macromolecule to prepare an ideal antibacterial polyester macromolecule; the protonation of the amino contains a positive charge structure, which can effectively penetrate into the bacterial cell membrane structure to cause the antibacterial mechanism of the biological macromolecule modification, so that the grafting abundance of the macromolecule amino is improved, and the antibacterial effect of the polyester macromolecule is enhanced.

Description

Technical Field

[0001] This invention relates to the field of biomedicine, specifically to an antibacterial dendritic polyester polymer, its preparation method, and its applications. Background Technology

[0002] Bacterial contamination, especially drug-resistant bacterial contamination, of implantable medical devices (such as catheters, pacemakers, cardiac stents, heart valves, and EEG electrodes) is one of the most common causes of hospital-acquired infections. Many patients frequently face life-threatening complications due to drug-resistant bacterial contamination. Effectively addressing pathogenic bacterial contamination on the surface of medical devices remains one of the most challenging clinical problems.

[0003] Using antibiotics to treat infections can greatly benefit patients. Generally, antibiotics are classified according to their structure into quinolones, β-lactams, macrolides, aminoglycosides, etc. In the process of fighting these antibiotics, bacteria have gradually evolved enzymes (such as β-lactamases) that can break them down, leading to antibiotic resistance. These resistant bacteria can pass on mutated genes to the next generation through various pathways, leading to the spread of drug-resistant bacteria. Therefore, continued overuse of antibiotics could potentially lead to a situation where no antibiotics are available. To date, antibiotic overuse has caused a series of serious public health events globally, especially the emergence of multidrug-resistant bacteria, which often causes malignant infections and worsens patient conditions. Common drug-resistant bacteria include Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, causing approximately 4.95 million deaths worldwide each year, of which about 1.25 million can be attributed to drug resistance. Therefore, there is an urgent need to develop an antibacterial agent that is not affected by bacterial endocrine enzymes. Summary of the Invention

[0004] To overcome the vulnerability of traditional antibiotics to bacterial endocrine enzymes, this invention provides an antibacterial dendritic polyester polymer, its preparation method, and its application. This invention utilizes the antibacterial mechanism of protonated amino groups containing positively charged structures that can effectively penetrate the bacterial cell membrane structure, thereby causing bacterial lysis. This modification of the biopolymer increases the grafting abundance of the polymeric amino groups and enhances the antibacterial effect of the polyester polymer.

[0005] This invention first provides a method for preparing dendritic polyester polymers, comprising the following steps:

[0006] (1) Polyethylene glycol, a carboxylic acid hydrophilic chain extender and 4-dimethylaminopyridine are reacted in a solvent to obtain product A; product A is added to petroleum ether and the lower layer solution is collected to obtain product B;

[0007] (2) Dissolve the product B and the amino acid protected by tert-butoxycarbonyl in a solvent and react to obtain product C; add the product C to petroleum ether and collect the lower layer solution to obtain product D;

[0008] (3) Dissolve the product D in trifluoroacetic acid, and the product obtained after the reaction is the dendritic polyester polymer.

[0009] In the above preparation method, the polyethylene glycol has the structural formula I, II, III or IV; wherein n is 50-10000000;

[0010]

[0011] The carboxylic acid hydrophilic chain extender is 2,2-dimethylolpropionic acid and / or 2,2-dimethylolbutyric acid;

[0012] The structural formulas of 2,2-dimethylolpropionic acid and 2,2-dimethylolbutyric acid are as follows:

[0013]

[0014] The solvent is anhydrous.

[0015] The amino acids protected by the tert-butoxycarbonyl group are N-tert-butoxycarbonyl-D-isoglutamine, BOC-L-4-methylphenylalanine, BOC-L-alloisoleucine, N-tert-butoxycarbonyl-L-methionine dicyclohexylamine salt, BOC-D-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, N,N'-bis-BOC-D-histidine, Boc-L-cyclohexylglycine, BOC-L-3,4-difluorophenylalanine, BOC-p-methylbenzenesulfonyl-D-arginine, Boc-D-asparagine, and S-acetyl Aminomethyl-N-tert-butoxycarbonyl-L-cysteine, Boc-Ser(Fmoc-Ile)-OH, N-A-tert-butoxycarbonyl-S-(9-fluorenmethyl)-L-cysteine, N-{[(2-methyl-2-propyl)oxy]carbonyl}-L-leucylglycine, N-(tert-butoxycarbonyl-L)-S-methyl-L-cysteine, BOC-L-3-trifluoromethylphenylalanine, BOC-D-tryptophan (NIN-formyl), Boc-D-Arg(Z)2-OH, (3S,7S) -7-Carboxy-3-[(tert-butoxy)methyl]-11,11-dimethyl-4,9-dioxo-5,10-dioxa-2,8-diazadodecanoic acid 1-fluorenylmethyl ester, Boc-ThpGly-OH, Boc-Glu(OBzl)-ONp, N-tert-butoxycarbonyl-O-benzyl-D-threonine, Boc-L-beta-homoproline, (R)-3-tert-butoxycarbonylamino-4-phenylbutyric acid, BOC-D-3,4-difluorophenylalanine, BOC-L-aspartic acid 4-tert-butyl-1-hydroxy-succinimide ester, Boc-Ala-Ala-OH, Boc-D-phenylglycine, (1S,4S)-4-tert-butoxycarbonylaminocyclohexanecarboxylic acid, Boc-Ser(Fmoc-Gly)-OH, N-tert-butoxycarbonyl-N-methyl-L-leucine, Boc-D-cyclohexylglycine, BOC-arginine, 4-tert-butoxycarbonylamino-4-carbamoylbutyric acid, Boc-D-Dap(Boc)-OH·DCHA, BOC-D-3,4,5-Trifluorophenylalanine, Boc-DL-Glu(OBzl)-OH, Boc-D-Glutamic Acid, Boc-L-4-Fluorophenylalanine, N-BOC-4-Aminobenzoic Acid, Boc-L-6-Hydroxyleucine, Tert-Butoxycarbonyl-Leucine Dicyclohexylamine Salt, N-BOC-O-Benzyl-DL-Serine, N-T-Butoxycarbonyl-N'-Aldehyde-L-Tryptophan, Boc-D-Asp(OMe)-OH, Boc-Phe-P ro-OH, Boc-D-Cys(Bzl)-OH, Boc-D-Isoleucine, BOC-L-Alanine N-Succinicotinamide, N-BOC-S-Triphenylmethyl-L-Cysteine ​​N-Succinimide, Boc-Lys-OtBu, BOC-O-Methyl-L-Threonine, BOC-D-4-Nitrophenylalanine, N-tert-Butoxycarbonyl-(N'-fluorenylmethoxycarbonyl)-D-Ornithine, N,N'-Bis-BOC-D-Ornithine BOC-L-3,4,5-trifluorophenylalanine, Boc-Ser-OBzl, BOC-glycine tert-butyl ester, N-[tert-butoxycarbonyl]-3-[(triphenylmethyl)thio]-L-valine, OC-L-aniline-4-nitrobenzene ester, Boc-Ser(Fmoc-Thr(tbu)-OH, Boc-Thr(Fmoc-Tyr(tBu))-OH, Boc-Tyr-OSu, Boc-4-amino-D-phenyl At least one of the following: alanine, N-BOC-4-methoxy-D-phenylalanine, N-BOC-3-hydroxy-L-phenylalanine, Boc-D-Lys(Boc)-OH, N,O-bis[(tert-butoxy)carbonyl]-L-tyrosine, tert-butoxycarbonyl-D-2,4-diaminobutyric acid, N-Boc-L-tert-leucine, and BOC-D-3-fluorophenylalanine; specifically, it may be tert-butoxycarbonyl-protected lysine Boc-Lys(Boc)-OH.

[0016] In step (1), the solvent is at least one selected from dichloromethane, chloroform, dichloroethane, anhydrous ethanol, anhydrous methanol, acetone, methyl ethyl ketone, tetrahydrofuran, xylene, acetonitrile, dimethyl sulfoxide, pyridine, and N,N-dimethylformamide; specifically, the solvent is dichloromethane and N,N-dimethylformamide; more specifically, the volume ratio of dichloromethane to N,N-dimethylformamide is 5:1.

[0017] In the above preparation method, in step (1), the equivalent ratio of polyethylene glycol, carboxylic acid hydrophilic chain extender and 4-dimethylaminopyridine is 1:1 to 10:1 to 10; specifically, it can be 1:5:5.

[0018] The polyethylene glycol accounts for 0.1% to 50% of the solvent by mass volume, in g / mL; specifically, it can be 20%.

[0019] In step (2), the equivalent ratio of product B to the tert-butyloxycarbonyl-protected amino acid is 1:1 to 5; specifically, it can be 1:1.66; wherein the equivalent of product B is calculated based on a carboxylic acid-type hydrophilic chain extender.

[0020] In step (2), the concentration of product B in the solvent is 0.01 to 0.9 mmol / mL, specifically 0.1 mmol / mL; wherein the molar number of product B is calculated based on a carboxylic acid-type hydrophilic chain extender.

[0021] In step (2), the solvent is at least one of dichloromethane, chloroform, dichloroethane, anhydrous ethanol, anhydrous methanol, acetone, methyl ethyl ketone, tetrahydrofuran, xylene, acetonitrile, dimethyl sulfoxide, pyridine, and N,N-dimethylformamide; specifically, it may be dichloromethane.

[0022] In step (3), the volume ratio of product D to trifluoroacetic acid is 1:1 to 50; specifically, it can be 1:6.25.

[0023] In the above preparation method, the reaction temperature in steps (1) to (3) is 30 to 100°C, specifically 30 to 40°C, or more specifically 37°C; and the reaction time is 2 to 24 hours, specifically 2 to 14 hours.

[0024] The solvent removal steps after collecting the lower layer solution in steps (1) and (2) of the above preparation method still need to be removed by rotary evaporation;

[0025] Specifically, the temperature of the rotary evaporation is 20–60°C; specifically, it can be 37°C.

[0026] The dendritic polyester polymer prepared by the above method.

[0027] The application of the aforementioned dendritic polyester polymer in the preparation of antibacterial agents also falls within the scope of protection of this invention.

[0028] Specifically, the bacteria are bacteria, more specifically Escherichia coli and / or Staphylococcus aureus.

[0029] The present invention provides an antibacterial agent comprising the aforementioned dendritic polyester polymer and a buffer solution.

[0030] In the above-mentioned antibacterial agents, the dendritic polyester polymer has a volume fraction of 5-80% in the antibacterial agent.

[0031] In the above-mentioned antibacterial agents, the buffer solution is PBS buffer solution, dilute hydrochloric acid buffer, phosphate buffer, phosphate buffered saline, Tris-hydrochloric acid buffer, glycine-hydrochloric acid buffer, disodium hydrogen phosphate-sodium citrate buffer, citrate-sodium hydroxide-hydrochloric acid buffer, citrate-sodium citrate buffer, disodium hydrogen phosphate-potassium dihydrogen phosphate buffer, potassium dihydrogen phosphate-sodium hydroxide buffer, boric acid-borax buffer, borax-sodium hydroxide buffer, or sodium carbonate-sodium bicarbonate buffer.

[0032] The present invention has the following beneficial effects:

[0033] The raw materials for preparing the polyester polymer of this invention are widely available, inexpensive, highly biocompatible, and have controllable grafting degree. Since dendritic polymers have many branching points and excellent flowability, this invention prepares an ideal antibacterial polyester polymer by grafting amino groups onto the branches of dendritic polymers. The polyester polymer of this invention has excellent antibacterial properties, and its antibacterial properties are not affected by bacterial endocrine enzymes. Attached Figure Description

[0034] Figure 1 The 1H NMR spectrum of the dendritic polyester polymer prepared in Example 1;

[0035] Figure 2 The image shows the carbon NMR spectrum of the dendritic polyester polymer prepared in Example 1.

[0036] Figure 3 This is a diagram illustrating the antibacterial effect of dendritic polyester polymers.

[0037] Figure 4 The antibacterial effect of dendritic polyester polymers against bacteria of different concentrations;

[0038] Figure 5 The effect of the dosage of dendritic polyester polymer on antibacterial effect;

[0039] Figure 6 The time-dependent antibacterial effect of dendritic polyester polymers. Detailed Implementation

[0040] The present invention will be further described in detail below with reference to specific embodiments. The embodiments given are only for illustrating the present invention and are not intended to limit the scope of the present invention.

[0041] Unless otherwise specified, the experimental methods described in the following examples are conventional methods.

[0042] Unless otherwise specified, all materials and reagents used in the following examples are commercially available.

[0043] The Escherichia coli used in the following examples is a Gram-negative Escherichia coli (E. coli), which is described in the literature (Artificial Nonenzymatic Antioxidant MXene Nanosheet-Anchored Injectable Hydrogel as a Mild Photothermal-Controlled Oxygen Release Platform for Diabetic Wound Healing, Yang Li et al., ACS Nano 2022, 16, 7486-7502). It is available to the public from Jiangsu University of Science and Technology, or obtained from the applicant with the consent of Jiangsu University of Science and Technology. The above-mentioned biological materials are only used to repeat the relevant experiments of this invention and shall not be used for other purposes.

[0044] The Staphylococcus aureus used is a Gram-positive Staphylococcus aureus (S. aureus), described in the literature (Artificial Nonenzymatic Antioxidant MXene Nanosheet-Anchored Injectable Hydrogel as a Mild Photothermal-Controlled Oxygen Release Platform for Diabetic Wound Healing, Yang Li et al., ACS Nano 2022, 16, 7486-7502). It is available to the public from Zhejiang University of Technology, or obtained from the applicant with the consent of Zhejiang University of Technology. The above-mentioned biological material is only used to repeat the relevant experiments of this invention and shall not be used for other purposes.

[0045] The structural formula of the polyethylene glycol used in the following examples is:

[0046] Example 1

[0047] In a round-bottom flask, polyethylene glycol (PEG) (M=6000) (10 g, 20%, g / mL), 2,2-dimethylolbutyric acid (0.740 g, 1.48%, g / mL), and 4-dimethylaminopyridine (0.610 g, 1.22%, g / mL) (PEG, 2,2-dimethylolbutyric acid, and 4-dimethylaminopyridine equivalent ratio 1:5:5) were added and dissolved in dichloromethane (45 mL) and N,N-dimethylformamide (5 mL). The mixture was stirred in a 37°C water bath for 12 h. The resulting product was then added dropwise to petroleum ether, and the lower layer was collected. The solvent was removed by rotary evaporation of the lower layer at 37°C (the equivalent of the product is expressed as 2,2-dimethylolbutyric acid). The molar amount was 0.005 mol. Then, 2.88 g (0.0083 mol) of tert-butyloxycarbonyl-protected lysine Boc-Lys(Boc)-OH (purchased from Nanjing Peptide Biotechnology Co., Ltd., catalog number 2483-46-7) was added and dissolved in 50 mL of dichloromethane. The mixture was stirred in a water bath at 37 °C for 12 h. The resulting solution was then added dropwise to petroleum ether, and the lower layer was collected. The organic solvent in the lower layer was removed by rotary evaporation at 37 °C. Approximately 8 mL of solution was obtained. The product was dissolved in 50 mL of trifluoroacetic acid and stirred at 37 °C for 4 h to obtain the final product, which was a pale yellow oil, namely the dendritic polyester polymer, with a yield of 75%.

[0048] The synthetic route is shown below:

[0049]

[0050] Figure 1 and Figure 2 The images show the 1H and 1C NMR spectra of the dendritic polyester polymer, respectively. Figure 1 and Figure 2 It can be seen that the chemical shift near 7.5 ppm in the 1H NMR spectrum is the amino hydrogen on the dendritic compound, the 160 ppm NMR spectrum is the C=O on the dendritic compound, and the peaks near 30-40 ppm show the characteristic peaks of the polyethylene glycol carbon skeleton.

[0051] Example 2

[0052] In a 48-well plate, 2 mL of Staphylococcus aureus suspension (inoculated in beef extract peptone broth and cultured until the optical density reached 0.5) was mixed with 1 mL of the dendritic polyester polymer prepared in Example 1 and incubated at 37°C for 24 h. An untreated Staphylococcus aureus suspension served as a blank. Then, 200 μL of the cultured bacterial solution was plated onto Luria-Bertani medium and incubated overnight at 37°C to obtain single colonies. The number of colony-forming units (CFU) was calculated. Bacterial proliferation was calculated based on the ratio of CFU to the blank for each sample.

[0053] See the diagram for the antibacterial effect of dendritic polyester polymer. Figure 3 , Figure 3 In the diagram, 'a' represents the control group for Staphylococcus aureus, and 'b' represents the experimental group for Staphylococcus aureus. Figure 3 It can be seen that dendritic polyester polymers have a significant inhibitory effect on the growth of Staphylococcus aureus.

[0054] Example 3

[0055] Different volumes of bacterial suspensions (Staphylococcus aureus or Escherichia coli, obtained by inoculating the bacteria in beef extract peptone broth and culturing to an optical density of 0.5) were mixed with 120 μL of the dendritic polyester polymer prepared in Example 1 and different volumes of PBS buffer solution (pH = 7.2) in 96-well plates. The mixtures were incubated at 37°C for 24 h. The bacterial suspension volumes were 20 μL, 40 μL, and 60 μL, respectively, with a total volume of 200 μL. The remainder was PBS buffer solution, which served as a blank control. The optical density before and after inhibition was measured using the OD method, and the inhibition rate of the dendritic polyester polymer against bacteria was calculated. Results are shown below. Figure 4 ,Depend on Figure 4 It can be seen that the inhibitory effect of dendritic polyester polymers on bacteria exhibits a dose-dependent effect.

[0056] Example 4

[0057] In a 96-well plate, 20 μL of bacterial suspension (Staphylococcus aureus or Escherichia coli, obtained by inoculating the bacteria in liquid culture medium and culturing to an optical density of 0.5) was mixed with different volumes of dendritic polyester polymer prepared in Example 1 and PBS buffer solution, respectively. The mixture was incubated at 37°C for 24 h. The amounts of dendritic polyester polymer used were 40 μL, 80 μL, and 120 μL, respectively, with a total volume of 200 μL. The remainder was PBS buffer solution. A 20 μL bacterial suspension + 180 μL PBS buffer solution was used as a blank. The optical density before and after inhibition was measured using the OD method, and the inhibition rate of the dendritic polyester polymer against the bacteria was calculated. All experiments were repeated six times, and the results were averaged.

[0058] See results Figure 5 ,Depend on Figure 5 It can be seen that the antibacterial effect against the three bacteria increases significantly with the increase of the amount of dendritic compounds, indicating the concentration dependence of dendritic polyester polymer antibacterial activity.

[0059] Example 5

[0060] In a 96-well plate, 40 μL of bacterial suspension (Staphylococcus aureus or Escherichia coli, obtained by inoculating the bacteria in liquid culture medium and culturing until the optical density value reaches 0.5) was mixed with 120 μL of the dendritic polyester polymer prepared in Example 1 and 40 μL of PBS buffer solution, and incubated at 37°C for 24 h, 48 h, and 72 h, respectively. 40 μL of bacterial suspension + 160 μL of PBS buffer solution served as a blank. The optical density before and after inhibition was measured using the OD method, and the inhibition rate of the dendritic hydrogel on bacteria was calculated. All experiments were repeated six times, and the results were averaged.

[0061] See results Figure 6 ,Depend on Figure 6 It can be seen that the twig compound has a long-lasting inhibitory effect on all three types of bacteria, and its antibacterial effect gradually improves over time.

Claims

1. A method for preparing a dendritic polyester polymer, comprising the following steps: (1) Polyethylene glycol, a carboxylic acid hydrophilic chain extender and 4-dimethylaminopyridine are reacted in a solvent to obtain product A; product A is added to petroleum ether and the lower layer solution is collected to obtain product B; (2) Dissolve the product B and the amino acid protected by tert-butoxycarbonyl in a solvent and react to obtain product C; add the product C to petroleum ether and collect the lower layer solution to obtain product D; (3) Dissolve the product D in trifluoroacetic acid, and the product obtained after the reaction is the dendritic polyester polymer; The polyethylene glycol has a structural formula of I, II, III, or IV; wherein... n is 50 to 10,000,000; I II III IV The carboxylic acid hydrophilic chain extender is 2,2-dimethylolpropionic acid and / or 2,2-dimethylolbutyric acid; The amino acids protected by the tert-butoxycarbonyl group are N-tert-butoxycarbonyl-D-isoglutamine, BOC-L-4-methylphenylalanine, BOC-L-alloisoleucine, N-tert-butoxycarbonyl-L-methionine dicyclohexylamine salt, BOC-D-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, N,N'-bis-BOC-D-histidine, Boc-L-cyclohexylglycine, BOC-L-3,4-difluorophenylalanine, BOC-p-methylbenzenesulfonyl-D-arginine, Boc-D-asparagine, and S-acetyl Aminomethyl-N-tert-butoxycarbonyl-L-cysteine, Boc-Ser(Fmoc-Ile)-OH, N-A-tert-butoxycarbonyl-S-(9-fluorenmethyl)-L-cysteine, N-{[(2-methyl-2-propyl)oxy]carbonyl}-L-leucylglycine, N-(tert-butoxycarbonyl-L)-S-methyl-L-cysteine, BOC-L-3-trifluoromethylphenylalanine, BOC-D-tryptophan (NIN-formyl), Boc-D-Arg(Z)2-OH, (3S,7S) -7-Carboxy-3-[(tert-butoxy)methyl]-11,11-dimethyl-4,9-dioxo-5,10-dioxa-2,8-diazadodecanoic acid 1-fluorenylmethyl ester, Boc-ThpGly-OH, Boc-Glu(OBzl)-ONp, N-tert-butoxycarbonyl-O-benzyl-D-threonine, Boc-L-beta-homoproline, (R)-3-tert-butoxycarbonylamino-4-phenylbutyric acid, BOC-D-3,4-difluorophenylalanine, BOC-L-aspartic acid 4-tert-butyl-1-hydroxy-succinimide ester, Boc-Ala-Ala-OH, Boc-D-phenylglycine, (1S,4S)-4-tert-butoxycarbonylaminocyclohexanecarboxylic acid, Boc-Ser(Fmoc-Gly)-OH, N-tert-butoxycarbonyl-N-methyl-L-leucine, Boc-D-cyclohexylglycine, BOC-arginine, 4-tert-butoxycarbonylamino-4-carbamoylbutyric acid, Boc-D-Dap(Boc)-OH·DCHA, BOC-D-3,4,5-Trifluorophenylalanine, Boc-DL-Glu(OBzl)-OH, BOC-D-Glutamic Acid, BOC-L-4-Fluorophenylalanine, N-BOC-4-Aminobenzoic Acid, BOC-L-6-Hydroxyleucine, Tert-Butoxycarbonyl Leucine Dicyclohexylamine Salt, N-BOC-O-Benzyl-DL-Serine, N-T-Butoxycarbonyl-N'-Aldehyde-L-Tryptophan, Boc-D-Asp(OMe)-OH, B Boc-Phe-Pro-OH, Boc-D-Cys(Bzl)-OH, Boc-D-Isoleucine, Boc-L-Alanine N-Succinimide, N-BOC-S-Triphenylmethyl-L-Cysteine ​​N-Succinimide, Boc-Lys-OtBu, Boc-O-Methyl-L-Threonine, Boc-D-4-Nitrophenylalanine, N-tert-Butoxycarbonyl-(N'-fluorenylmethoxycarbonyl)-D-Ornithine, N N'-bis-BOC-D-ornithine, BOC-L-3,4,5-trifluorophenylalanine, Boc-Ser-OBzl, BOC-glycine tert-butyl ester, N-[tert-butoxycarbonyl]-3-[(triphenylmethyl)thio]-L-valine, OC-L-aniline-4-nitrobenzene ester, Boc-Ser(Fmoc-Thr(tbu)-OH, Boc-Thr(Fmoc-Tyr(tBu))-OH, B At least one of the following: Boc-Tyr-OSu, Boc-4-amino-D-phenylalanine, N-BOC-4-methoxy-D-phenylalanine, N-BOC-3-hydroxy-L-phenylalanine, Boc-D-Lys(Boc)-OH, N,O-bis[(tert-butoxy)carbonyl]-L-tyrosine, tert-butoxycarbonyl-D-2,4-diaminobutyric acid, N-Boc-L-tert-leucine, and Boc-D-3-fluorophenylalanine; In step (1), the equivalent ratio of polyethylene glycol, carboxylic acid hydrophilic chain extender and 4-dimethylaminopyridine is 1:1~10:1~10; The polyethylene glycol accounts for 0.1% to 50% of the solvent by mass volume, in g / mL; In step (2), the equivalent ratio of product B to the amino acid protected by tert-butoxycarbonyl is 1:1~5; wherein the equivalent of product B is calculated as a carboxylic acid hydrophilic chain extender.

2. The preparation method according to claim 1, characterized in that: In steps (1) and (2), the solvent is at least one of dichloromethane, chloroform, dichloroethane, anhydrous ethanol, anhydrous methanol, acetone, methyl ethyl ketone, tetrahydrofuran, xylene, acetonitrile, dimethyl sulfoxide, pyridine, and N,N-dimethylformamide.

3. The preparation method according to claim 1 or 2, characterized in that: In step (3), the volume ratio of product D to trifluoroacetic acid is 1:10~50.

4. The preparation method according to claim 1 or 2, characterized in that: In steps (1) to (3), the reaction temperature is 30 to 100 °C and the time is 2 to 24 h.

5. The preparation method according to claim 1 or 2, characterized in that: After collecting the lower layer solution in steps (1) and (2), there is a step of rotary evaporation to remove the solvent.

6. The preparation method according to claim 5, characterized in that: The temperature of the rotary evaporation is 20~60℃.

7. The dendritic polyester polymer prepared by the preparation method according to any one of claims 1-6.

8. The use of the dendritic polyester polymer according to claim 7 in the preparation of antibacterial agents.

9. An antibacterial agent comprising the dendritic polyester polymer of claim 7 and a buffer solution.

10. The antibacterial agent according to claim 9, characterized in that: The dendritic polyester polymer has a volume fraction of 5-80% in the antibacterial agent.

11. The antibacterial agent according to claim 9 or 10, characterized in that: The buffer solution is PBS buffer solution, dilute hydrochloric acid buffer, phosphate buffer, phosphate-buffered saline, Tris-hydrochloric acid buffer, glycine-hydrochloric acid buffer, disodium hydrogen phosphate-sodium citrate buffer, citrate-sodium hydroxide-hydrochloric acid buffer, citrate-sodium citrate buffer, disodium hydrogen phosphate-potassium dihydrogen phosphate buffer, potassium dihydrogen phosphate-sodium hydroxide buffer, boric acid-borax buffer, borax-sodium hydroxide buffer, or sodium carbonate-sodium bicarbonate buffer.

Images