Antibacterial poly (beta-amino ester) as well as preparation method and application thereof

Abstract

The invention discloses antibacterial poly (beta-amino ester) and a preparation method and application thereof, poly (beta-amino ester) macromolecules simultaneously have amino positive charges and fluorine-containing hydrophobic components, existence of the positive charges enables the poly (beta-amino ester) macromolecules to be more easily combined with negatively charged bacterial cell membranes and to be enriched, and the hydrophobic components can enable the poly (beta-amino ester) macromolecules to be inserted into cell membrane phospholipid bilayers, so that the antibacterial effect is improved. Therefore, bacteria are effectively killed, and drug resistance is not easily caused. The polymer has high antibacterial property and low hemolytic toxicity, can be self-assembled into nano particles, and can be combined with antibiotics in an antibiotic loading manner to improve the treatment effect. The compound can be synthesized through simple steps, the reaction condition is simple, the preparation cost, the raw material cost and the application cost are very low, and the compound has a very good prospect when being applied to medicines for treating or preventing diseases caused by bacteria.

Description

Technical Field

[0001] The present invention relates to the technical field of medical macromolecules, and in particular to an antibacterial poly(β-amino ester) and a preparation method and application thereof. Background Art

[0002] Due to the tremendous selective pressure exerted by humans' indiscriminate use of antibiotics, many bacteria have gradually developed resistance. Due to excessive exposure to antibiotics, this resistance development process continues not only in bacterial populations present in human communities, but also in animal pathogens and even environmental microorganisms. This has led to the gradual ineffectiveness of antibiotics that previously demonstrated bactericidal activity at extremely low concentrations. As the availability of natural antibiotics continues to deplete, the development of new antimicrobial molecules is urgently needed to address the crisis of antibiotic-resistant bacteria.

[0003] To this end, researchers have designed antibacterial polymers in recent years by introducing positively charged and hydrophobic components into polymers. CN116554470A discloses an imidazole-based polycationic antibacterial polymer and its preparation and application. The positive charge carried by the quaternized cationic imidazolium salt group adsorbs onto the negatively charged bacterial cell membrane, while the hydrophobic segments carried by the polymer can insert into and disrupt the bacterial cell membrane, thereby achieving an antibacterial effect. Experiments have found that this polymer exhibits excellent antibacterial and bactericidal properties under body temperature incubation conditions, and has the potential to be used in the human body to combat microbial infections.

[0004] CN 119431639 A discloses a cyclodextrin-grafted N-cationic bornyl ester polymer antibacterial material. This polymer antibacterial material has more efficient antibacterial activity, broad-spectrum antibacterial properties and good biocompatibility. It can be used in the biomedical field and in the preparation of antibacterial materials such as fruit preservation materials, antibacterial coatings, and antibacterial fabrics.

[0005] However, the preparation process of these polymers is often complex, requiring relatively stringent reaction conditions, and little research has been conducted on their hemolytic toxicity. Therefore, it is urgent to develop polymers with simple synthesis steps that combine high antibacterial properties with low hemolytic toxicity. Summary of the Invention

[0006] The present invention addresses the problem that the antibacterial activity and toxicity of antibacterial polymers are often contradictory, and provides a class of antibacterial poly (β-amino esters). This class of antibacterial polymers has excellent antibacterial activity and low hemolytic toxicity, and can be used to treat or prevent diseases caused by bacteria.

[0007] To achieve the above object, the technical solution adopted by the present invention is:

[0008] A class of antimicrobial poly(β-amino esters) having a structure as shown in any one of Formulas H1-H3:

[0009] H1:

[0010]

[0011] H2:

[0012]

[0013] H3:

[0014]

[0015] Wherein, x:y:z of H1=(5-7):(2-4):(0.5-2), and the weight average molecular weight of H1 is 5000-50000;

[0016] H2's x:y:z=8:(0.5-2):(0.5-2), H2's weight average molecular weight is 5000-50000;

[0017] The x:y:z of H3 is 8:(0.5-2):(0.5-2), and the weight average molecular weight of H3 is 5000-50000.

[0018] The antibacterial poly(β-amino ester) provided in the present invention has both amino positive charges and fluorine-containing hydrophobic components in its structure. The presence of positive charges makes it easier to bind to and enrich the negatively charged bacterial cell membrane, while the hydrophobic components enable it to insert into the cell membrane phospholipid bilayer, thereby effectively killing bacteria and not easily inducing drug resistance.

[0019] Preferably, x:y:z in H1=6:3:1, and the weight average molecular weight of H1 is 5000-8000;

[0020] Preferably, x:y:z in H2=8:1:1, and the weight average molecular weight of H1 is 5000-8000;

[0021] Preferably, x:y:z in H3=8:1:1, and the weight average molecular weight of H1 is 5000-8000;

[0022] The present invention also provides a method for preparing the antibacterial poly(β-amino ester), comprising the steps of:

[0023] N-Boc-ethylenediamine, 1-amino-2-methyl-2-propanol, 17-amino-3,6,9,12,15-pentaoxaheptadecanol and neopentyl glycol diacrylate were polymerized in a solution, and the BOC protection was removed and the product was washed and purified to obtain compound H1;

[0024] Alternatively, N-Boc-ethylenediamine, 2,2,3,3,4,4,4-heptafluorobutylamine, 2,2-dimethyl-3-aminopropionamide and neopentyl glycol diacrylate are polymerized in a solution, and the BOC protection is removed and the product is washed and purified to obtain compound H2;

[0025] Alternatively, N-Boc-ethylenediamine, 2,2,3,3,4,4,4-heptafluorobutylamine, amino-tetraethylene glycol and 1,3-phenylenebis(methylene)diacrylate are polymerized in a solution, and after removing the BOC protection, the product is washed and purified to obtain compound H3.

[0026] Preferably, the raw materials are dissolved in a solvent to form a solution before the reaction, and then mixed for reaction. The solvent includes any one or more common solvents such as N,N-dimethylformamide and dimethyl sulfoxide.

[0027] In the preparation method, the polymerization reaction temperature is 50-150° C., the reaction time is 12-36 hours, and the molar ratio of the acrylate raw material to the amine raw material is (1.05-1.3):1.

[0028] During the preparation of H1, the molar ratio of N-Boc-ethylenediamine, 1-amino-2-methyl-2-propanol, and 17-amino-3,6,9,12,15-pentaoxaheptadecanol is (5-7):(2-4):(0.5-2);

[0029] During the preparation of H2, the molar ratio of N-Boc-ethylenediamine, 2,2,3,3,4,4,4-heptafluorobutylamine, and 2,2-dimethyl-3-aminopropionamide is 8:(0.5-2):(0.5-2);

[0030] During the preparation of H3, the molar ratio of N-Boc-ethylenediamine, 2,2,3,3,4,4,4-heptafluorobutylamine, and amino-tetraethylene glycol is 8:(0.5-2):(0.5-2).

[0031] The present invention also provides use of the antibacterial poly(β-amino ester) in preparing medicines for treating and / or preventing bacterial infections.

[0032] The bacteria are Gram-positive bacteria and / or Gram-negative bacteria.

[0033] The bacteria are Staphylococcus aureus and / or Acinetobacter baumannii.

[0034] The present invention also provides the use of the antibacterial poly (β-amino ester) in combination with an antibiotic in the preparation of a drug for treating and / or preventing bacterial infection.

[0035] The antibiotics include any one or more of β-lactams, macrolides, aminoglycosides, and tetracyclines.

[0036] Preferably, the antibiotic is one or more of penicillin G sodium and penicillin G potassium.

[0037] The present invention also provides a nanocomposite of an antibacterial poly(β-amino ester) and an antibiotic, comprising the antibacterial poly(β-amino ester) and the antibiotic; preferably, the mass ratio of the antibacterial poly(β-amino ester) to the antibiotic in the nanocomposite is (0.5-2):(0.5-2).

[0038] The present invention also provides a method for preparing a nanocomposite of an antimicrobial poly(β-amino ester) and an antibiotic as described in claim 8, comprising the steps of mixing the antimicrobial poly(β-amino ester) and the antibiotic in a solvent. The antimicrobial poly(β-amino ester) of the present invention can self-assemble into nanoparticles, which, after mixing with the antibiotic, self-assemble with the antibiotic to form a nanocomposite.

[0039] The present invention also provides a drug for treating and / or preventing bacterial infection, comprising antibacterial poly(β-amino ester); or, comprising antibacterial poly(β-amino ester) and antibiotics; or, comprising the nanocomposite.

[0040] Compared with the prior art, the present invention has the following beneficial effects:

[0041] (1) Through extensive research, the present invention unexpectedly discovered that the above three polymers have high antibacterial properties and low hemolytic toxicity, can self-assemble into nanoparticles, and are used in drugs for treating or preventing diseases caused by bacteria.

[0042] (2) In addition to being used directly as an antibacterial drug, the present invention can also be used in combination with antibiotics by loading antibiotics to improve the therapeutic effect.

[0043] (3) The antibacterial polymer of the present invention can be synthesized through simple steps and reaction conditions. The preparation cost, raw material cost and application cost are very low, and it has very good application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0044] Figure 1 The chemical reaction formula for preparing the antibacterial poly (β-amino ester) H1 compound in Example 1 is shown.

[0045] Figure 2 This is the NMR spectrum of the antibacterial poly (β-amino ester) H1 compound prepared in Example 1.

[0046] Figure 3 This is the chemical reaction formula for preparing the antibacterial poly (β-amino ester) H2 compound in Example 2.

[0047] Figure 4 This is the NMR spectrum of the antibacterial poly (β-amino ester) H2 compound prepared in Example 2.

[0048] Figure 5 The chemical reaction formula for preparing the antibacterial poly (β-amino ester) H3 ​​compound in Example 3 is shown.

[0049] Figure 6 This is the NMR spectrum of the antibacterial poly (β-amino ester) H3 ​​compound prepared in Example 3.

[0050] Figure 7 The hemolysis rate-concentration curves and cell survival rate-concentration curves of different antibacterial poly (β-amino ester) polymers are shown.

[0051] Figure 8 It is a comparison of the resistance of different antibacterial poly (β-amino ester) polymers and common antibiotics.

[0052] Figure 9 It is a comparison of the in vivo antibacterial effects of different antibacterial poly (β-amino ester) polymers and common antibiotics.

[0053] Figure 10 The antibacterial effect of different antibacterial poly (β-amino ester) polymers combined with antibiotic PG.

[0054] Figure 11 The results are for the comparison of the in vivo antibacterial effect of the antibacterial poly (β-amino ester) H2 polymer in combination with the antibiotic PG (comparison of bacterial loads in organ homogenates 24 hours after infection in a lethal MRSA peritonitis model). DETAILED DESCRIPTION

[0055] In order to make the purpose, technical solutions and advantages of the present invention clearer, the present invention is further described in detail below in conjunction with embodiment. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention. Those skilled in the art will make modifications or equivalent substitutions based on understanding the technical solution of the present invention, without departing from the spirit and scope of the technical solution of the present invention, and all should be encompassed within the protection scope of the present invention.

[0056] The raw materials used in the following specific embodiments are all purchased from the market.

[0057] Example 1

[0058] In this study, the Michael addition reaction between diacrylate and amine was used to synthesize poly(β-amino ester). The synthesis steps of polymer H1 were as follows: the feed ratio of total diacrylate to amine raw materials was set at 1.2:1.

[0059] First, 24 μL of N-Boc-ethylenediamine (3 M in N,N-dimethylformamide (DMF), 12 μL of 1-amino-2-methyl-2-propanol (3 M in DMF), and 4 μL of 17-amino-3,6,9,12,15-pentaoxaheptadecanol (3 M in DMF) were pipetted sequentially into a reaction vial containing 48 μL of neopentyl glycol diacrylate (3 M in DMF).

[0060] The reaction flask was then heated to 90°C and magnetic stirring was turned on to continue the reaction for 24 hours. After 24 hours of polymerization, 80 μL of hydrofluoric acid was added to the solution and continued to stir at room temperature overnight to remove the BOC protecting group. After the deprotection reaction was completed, the crude product solution was precipitated in ether three times, and the supernatant was discarded to purify the polymer. The reaction equation is as follows Figure 1 The NMR spectrum of the product is shown in Figure 2 The tested polymer had a weight average molecular weight of 6000 and a polymer dispersibility index of 1.09.

[0061] Example 2

[0062] Polymer H2 synthesis steps: The total diacrylate to amine feed ratio was set at 1.2:1. First, 32 μL of N-Boc-ethylenediamine (3 M in DMF), 4 μL of 2,2,3,3,4,4,4-heptafluorobutylamine (3 M in DMF), and 4 μL of 2,2-dimethyl-3-aminopropionamide (3 M in DMF) were pipetted sequentially into a reaction vial containing 48 μL of neopentyl glycol diacrylate (3 M in DMF).

[0063] The reaction flask was then heated to 90°C and magnetic stirring was turned on to continue the reaction for 24 hours. After 24 hours of polymerization, 80 μL of hydrofluoric acid was added to the solution and continued to stir at room temperature overnight to remove the BOC protecting group. After the deprotection reaction was completed, the crude product solution was precipitated in ether three times, and the supernatant was discarded to purify the polymer. The reaction equation is as follows Figure 3 The NMR spectrum of the polymer product is shown in Figure 4 The tested polymer had a weight average molecular weight of 7100 and a polymer dispersibility index of 1.11.

[0064] Example 3

[0065] Synthesis steps of polymer H3: The feed ratio of total diacrylate to amine is set to 1.2:1. First, 32 μL of N-Boc-ethylenediamine (configured in DMF at a concentration of 3M), 4 μL of 1-amino-2-methyl-2-propanol (configured in DMF at a concentration of 3M) and 4 μL of amino-tetraethylene glycol (configured in DMF at a concentration of 3M) were added in sequence with a pipette to a reaction bottle containing 48 μL of 1,3-phenylenebis(methylene)diacrylate (configured in DMF at a concentration of 3M). The reaction bottle was then heated to 90°C, and magnetic stirring was turned on to continue the reaction for 24 hours. After 24 hours of polymerization, 80 μL of hydrofluoric acid was added to the solution, and stirring was continued at room temperature overnight to remove the BOC protecting group. After the deprotection reaction was completed, the crude product solution was precipitated in ether three times, and the supernatant was discarded to purify the polymer. The reaction equation is as follows Figure 5 The NMR spectrum of the polymer product is shown in Figure 6 The tested polymer had a weight average molecular weight of 7100 and a polymer dispersibility index of 1.11.

[0066] In vitro antibacterial and hemolytic toxicity of antimicrobial polymers

[0067] 1. Determination of Minimum Inhibitory Concentration (MIC)

[0068] Fresh methicillin-resistant Staphylococcus aureus (MRSA) was incubated in tryptic soy broth (TSB) overnight in a shaker (120 rpm, 37°C). The incubation solution was then calibrated to 10 using a microplate reader. 5 To determine the minimum inhibitory concentration (MIC), the purified polymer was diluted with DMSO to 2.56 mg / mL. 195 μL of the MRSA suspension was added to a sterile 96-well plate. 5 μL of the test polymer solution was then added to each well, resulting in a gradient dilution from 32 μg / mL to 4 μg / mL. Three replicates were set up for each group. The plates were sealed with sealing film and incubated on a shaker at 37°C for 9 hours. A sterile TSB solution served as the control group. Complete clarity of the solution was used as the criterion for determining the MIC. The MIC values ​​for HI, H2, and H3 against MRSA were all 8 μg / mL.

[0069] Take fresh Acinetobacter baumannii (Ab) in MH broth (MHB) and incubate overnight in a shaker (120 rpm, 37°C). Then take the incubation solution and calibrate it to 10 5To determine the minimum inhibitory concentration (MIC), the purified polymer was diluted with DMSO to 2.56 mg / mL. 195 μL of the Ab suspension was added to a sterile 96-well plate. 5 μL of the test polymer solution was then added to each well, resulting in a gradient dilution from 32 μg / mL to 4 μg / mL. Three replicates were set up for each group. The plates were sealed with sealing film and incubated on a shaker at 37°C for 9 hours. A sterile TSB solution served as the control group. Complete clarity of the solution was used as the criterion for determining the MIC. The MIC values ​​for HI, H2, and H3 against the Ab were all 8 μg / mL.

[0070] 2. Half hemolytic concentration (HC 50 ) and half-maximal inhibitory concentration (IC 50 )

[0071] Fresh New Zealand rabbit blood was used to prepare a 4% red blood cell suspension using the same method described above. 195 μL of the red blood cell suspension was added to each well of a 96-well plate. Subsequently, 5 μL of the purified polymer solution was added to each well using a dispenser, resulting in final polymer concentrations of 8 μg / mL, 16 μg / mL, 32 μg / mL, 64 μg / mL, 128 μg / mL, 200 μg / mL, 256 μg / mL, 400 μg / mL, and 512 μg / mL, respectively. A negative control group was treated with 5 μL of PBS, while a positive control group was treated with 5 μL of 0.4% Triton X-100. The plates were sealed with sealing film and incubated in a 37°C shaker for 1 hour. After incubation, the plates were centrifuged at 4°C (1500 RPM, 10 min). After centrifugation, 100 μL of supernatant was gently pipetted into a new 96-well plate using a dispenser. The OD value at 576 nm was measured using a microplate reader, and the hemolysis rate of the polymer at each concentration was calculated. Finally, the hemolysis rate-concentration curve was fitted to obtain the polymer concentration at half hemolysis.

[0072] L929 mouse fibroblasts were cultured in DMEM medium containing 10% serum. The cells were seeded in a 96-well plate at a density of 8,000 cells per well. After incubation for 24 hours, the medium was removed, 195 μL of fresh medium was added to each well, and 5 μL of pre-prepared polymer solution of different concentrations was added. The culture medium was discarded after a further 24 hours of incubation, and 100 μL of DMEM containing 10% CCK-8 reagent was added to each well. After incubation for 1 hour, the absorbance (OD value) was measured at 450 nm using a microplate reader. The curve of the relationship between cell viability and concentration was fitted to determine the polymer concentration that makes 50% of the cells survive, that is, IC 50 Value. Figure 7 As shown, HC of H1, H2, and H3 50The values ​​are: 168μg / mL, >512μg / mL, 266μg / mL. IC values ​​of H1, H2, and H3 are: 50 The values ​​were: 53μg / mL, 162μg / mL, 109μg / mL respectively.

[0073] 3. Drug Resistance Determination

[0074] The drug resistance test was slightly modified according to the MIC test method. First, fresh MRSA strains were incubated in tryptic soy broth (TSB) at 37°C and 120rpm overnight. Subsequently, the bacterial suspension was diluted and adjusted to a concentration of 1×105 CFU / mL. 195 μL of this bacterial suspension was added to each well of a 96-well plate, and 5 μL of the polymer solution to be tested (final concentration of 32 μg / mL) or the antibiotic solution to be tested (penicillin G sodium final concentration of 128 μg / mL, streptomycin or vancomycin final concentration of 32 μg / mL) was added. The 96-well plate containing the bacterial suspension was further incubated at 37°C for 9 hours, and the MIC value of the day was recorded. For each sample to be tested, a sample was taken from the turbid bacterial solution at sub-MIC concentration, diluted 400 times in TSB medium, and incubated overnight. The above cycle was repeated every 24 hours for a total of 28 days. The results are shown in Figure 2. Figure 8 As shown, it can be seen that compared with streptomycin and vancomycin, the target polymer H1-H3 is less likely to induce drug resistance.

[0075] In vivo antibacterial effect of antibacterial polymers

[0076] Healthy female ICR mice (18-20 g) were used in the experiment. On day 0, the mice were anesthetized with isoflurane and MRSA suspension (10 8 CFU / mL, 60 μL). Successfully infected mice were then randomly divided into five groups and administered H1, H2, H3, streptomycin (SM), and vancomycin (VM) via tail vein injection on day 1. PBS served as a control group. On day 2, mice were euthanized, and lung tissue was collected and documented. The collected lung tissue was then homogenized and colony counts were performed.

[0077] like Figure 9 As shown, the lungs of the untreated PBS-treated control group appeared unhealthy dark red in spots, indicating a poor treatment effect. The lungs of the polymer H1-3-treated group appeared healthy pink. Further tissue homogenate plate counts showed that while VM could inhibit MRSA infection in the lungs to some extent, the effect was not ideal in the short term. The polymer H1-3-treated group showed significant improvement in bacterial infection.

[0078] Antimicrobial polymers and antibiotics work synergistically

[0079] 1. Checkerboard antibacterial experiment

[0080] After determining the minimum inhibitory concentrations (MICs) of the antimicrobial polymers, a checkerboard antibacterial experiment was conducted against methicillin-resistant Staphylococcus aureus (MRSA) and penicillin G sodium (PG). The experiment was conducted in a 96-well plate, and the concentration of PG was diluted along the vertical gradient, decreasing from 128μg / mL to 8μg / mL; the polymer concentration was diluted along the horizontal gradient, with the concentration range of H1 and H3 ranging from 16μg / mL to 1μg / mL, and the concentration range of H2 ranging from 32μg / mL to 2μg / mL. In addition, the concentrations of polymer and PG in the last row and the last column were both 0μg / mL. The samples were incubated at 37°C for 9 hours, and all experiments were repeated three times independently to ensure the reproducibility and reliability of the data.

[0081] like Figure 10 The results showed that there was a synergistic effect between the target polymer and penicillin G, which significantly enhanced the sensitivity of MRSA to penicillin.

[0082] 2. Lethal MRSA Infection Peritonitis Model

[0083] The H2-PG complex was prepared by mixing H2 with an aqueous solution of penicillin G sodium in equal proportions, vortexing for 30 seconds at room temperature and then allowing to rest for 5 minutes. To further evaluate the in vivo anti-infective efficacy of the H2-PG nanocomplex, this study employed a neutropenic mouse peritonitis model. This model is a highly standardized and reproducible preclinical approach. Compared to respiratory infection models, it is more likely to induce systemic disease, such as sepsis, placing higher demands on the effectiveness of therapeutic strategies. Prior to infection, mice received cyclophosphamide injection to induce immunosuppression. On day 4, infection was established by intraperitoneal injection of 1×10 CFU of MRSA. Subsequently, mice received different treatment regimens: the H2, PG, and SM groups received intraperitoneal injections of the corresponding drugs at a dose of 10 mg / kg, while the H2-PG group received 5 mg / kg of the nanocomplex. Twenty-four hours later, mice were sacrificed, and blood was collected. Liver, kidney, spleen, and lung tissues were homogenized and subsequently analyzed for bacterial quantification.

[0084] like Figure 11 The results showed that compared with the control group, the average number of colonies in the organs of mice in the H2, PG, SM and H2-PG nanocomplex groups decreased by 1.2, 0.9, 2.5 and 2.3 orders of magnitude, respectively, and the H2-PG nanocomplex exhibited the most potent antibacterial effect.

Claims

1. An antimicrobial poly(β-amino ester), characterized in that Having a structure as shown in any one of formulas H1-H3: H1： H2： H3： Wherein, x:y:z of H1=(5-7):(2-4):(0.5-2), and the weight average molecular weight of H1 is 5000-50000; H2's x:y:z=8:(0.5-2):(0.5-2), H2's weight average molecular weight is 5000-50000; The x:y:z of H3 is 8:(0.5-2):(0.5-2), and the weight average molecular weight of H3 is 5000-50000.

2. A method for preparing the antibacterial poly (β-amino ester) according to claim 1, characterized in that: Including steps: N-Boc-ethylenediamine, 1-amino-2-methyl-2-propanol, 17-amino-3,6,9,12,15-pentaoxaheptadecanol and neopentyl glycol diacrylate were polymerized in a solution, and the BOC protection was removed and the product was washed and purified to obtain compound H1; Alternatively, N-Boc-ethylenediamine, 2,2,3,3,4,4,4-heptafluorobutylamine, 2,2-dimethyl-3-aminopropionamide and neopentyl glycol diacrylate are polymerized in a solution, and the BOC protection is removed and the product is washed and purified to obtain compound H2; Alternatively, N-Boc-ethylenediamine, 2,2,3,3,4,4,4-heptafluorobutylamine, amino-tetraethylene glycol and 1,3-phenylenebis(methylene)diacrylate are polymerized in a solution, and after removing the BOC protection, the product is washed and purified to obtain compound H3.

3. The method for preparing the antibacterial poly (β-amino ester) according to claim 2, wherein: The polymerization reaction temperature is 50-150° C., and the reaction time is 12-36 hours. The molar ratio of the acrylate raw material to the amine raw material is (1.05-1.3):

1. During the preparation of H1, the molar ratio of N-Boc-ethylenediamine, 1-amino-2-methyl-2-propanol, and 17-amino-3,6,9,12,15-pentaoxaheptadecanol is (5-7):(2-4):(0.5-2); During the preparation of H2, the molar ratio of N-Boc-ethylenediamine, 2,2,3,3,4,4,4-heptafluorobutylamine, and 2,2-dimethyl-3-aminopropionamide is 8:(0.5-2):(0.5-2); During the preparation of H3, the molar ratio of N-Boc-ethylenediamine, 2,2,3,3,4,4,4-heptafluorobutylamine, and amino-tetraethylene glycol is 8:(0.5-2):(0.5-2).

4. Use of the antibacterial poly (β-amino ester) according to claim 1 in the preparation of a medicament for treating and / or preventing bacterial infection.

5. The use according to claim 4, characterized in that The bacteria are Gram-positive bacteria and / or Gram-negative bacteria; preferably, the bacteria are Staphylococcus aureus and / or Acinetobacter baumannii.

6. Use of the antibacterial poly (β-amino ester) according to claim 1 in combination with an antibiotic in the preparation of a medicament for treating and / or preventing bacterial infection.

7. The use according to claim 6, characterized in that: The antibiotics include any one or more of β-lactams, macrolides, aminoglycosides, and tetracyclines; Preferably, the antibiotic is one or more of penicillin G sodium and penicillin G potassium.

8. A nanocomposite of an antimicrobial poly(β-amino ester) and an antibiotic, characterized in that The nanocomposite comprises the antibacterial poly(β-amino ester) according to claim 1 and an antibiotic; preferably, the mass ratio of the antibacterial poly(β-amino ester) to the antibiotic in the nanocomposite is (0.5-2):(0.5-2).

9. A method for preparing the nanocomposite of antibacterial poly(β-amino ester) and antibiotic according to claim 8, characterized in that: The method comprises the following steps: mixing antibacterial poly (beta-amino ester) and antibiotics in a solvent.

10. A drug for treating and / or preventing bacterial infection, characterized in that The invention comprises the antibacterial poly(β-amino ester) of claim 1; or comprises the antibacterial poly(β-amino ester) of claim 1 and an antibiotic; or comprises the nanocomposite of claim 8.

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