Janus-type hyperbranched polyurea and preparation method and application thereof

Abstract

The application provides a Janus hyperbranched polyurea and a preparation method and application thereof, the Janus hyperbranched polyurea has two functional subareas with clear boundaries, and the two sides are respectively quaternary ammonium groups with antibacterial properties and catechol groups with adhesion properties. Meanwhile, the Janus hyperbranched structure can make the functional groups of the material subarea, and then the functions can be efficiently exerted. Therefore, the Janus antibacterial hyperbranched polyurea can modify various biomaterials (metal, ceramic and synthetic polymer) to prepare an antibacterial surface through a soaking method or other methods, has broad-spectrum antibacterial properties, can cover various gram-positive bacteria and gram-negative bacteria, and has wide potential in clinical application.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a Janus-type hyperbranched polyurea, its preparation method, and its application. Background Technology

[0002] Iatrogenic infections (HAIS) refer to new infections contracted by patients during medical services due to exposure to the medical environment or procedures. Traditional methods for preventing clinical infections include the application of aseptic techniques and systemic antibiotic treatment, but these have not yielded highly satisfactory results. When medical devices (such as orthopedic implants, vascular stents, and artificial heart valves) are contaminated, the success rate of systemic antibiotic treatment is only 22-37%. Furthermore, systemic administration of antibiotics often requires high doses, which can cause cytotoxicity and side effects on surrounding tissues, and further exacerbate bacterial resistance. Throughout the entire infection process, the initial adhesion of bacteria to the material surface plays a decisive role; if this stage can be addressed or prevented, the cost of infection control can theoretically be minimized. A corresponding strategy is to develop simple and effective antimicrobial modified surfaces.

[0003] Quaternary ammonium cationic polymers are a class of novel bactericidal materials with excellent performance. They adsorb onto bacterial cell walls through electrostatic interactions, leading to membrane damage, cytoplasmic leakage, and bacterial death. Various methods have been developed to bind antibacterial agents to material surfaces, such as surface-initiated polymerization, reactions between specific functional groups, or layer-by-layer self-assembly. While these traditional methods have proven effective, they are typically applicable only to single surfaces, and the coating process is cumbersome, significantly limiting their application scenarios. In recent years, mussel chemistry has been recognized as a very promising surface modification method. The catechol-based substance 3,4-dihydroxy-L-phenylalanine it uses can induce strong surface adhesion on various surfaces, thus becoming a universal adhesion medium. Currently, coating strategies based on mussel chemistry mainly focus on the "coating first, then grafting" approach. This approach suffers from drawbacks such as the potential for mixed reactions and the complexity of the coating process. Summary of the Invention

[0004] To overcome at least one technical problem existing in the prior art, one objective of the present invention is to provide a Janus-type hyperbranched polyurea. A second objective of the present invention is to provide a method for preparing the aforementioned Janus-type hyperbranched polyurea. A third objective of the present invention is to provide applications of the aforementioned Janus-type hyperbranched polyurea.

[0005] This invention innovatively proposes a catechol-modified multifunctional Janus antibacterial hyperbranched polyurea. Through molecular design, an asymmetric spatial distribution of chemical composition is achieved within the hyperbranched polyurea system, with antibacterial quaternary ammonium groups on one side and adhesive catechol groups on the other. Therefore, the Janus antibacterial hyperbranched polyurea of ​​this invention can be used to modify various biomaterials (metals, ceramics, synthetic polymers) to prepare antibacterial surfaces via an immersion method, showing broad potential for clinical applications.

[0006] To achieve the above objectives, the technical solution adopted by the present invention is as follows: The first aspect of this invention provides a Janus-type hyperbranched polyurea, the structural formula of which is shown in Formula I:

[0007] Formula I Each R is independently represented by r2, , or ; r1 is r2 is ; The connection point is indicated by ⊕; the positive charge symbol is indicated by ⊕; each R1 is independently C4-C. 12 Alkyl groups.

[0008] Preferably, R is .

[0009] Preferably, C4-C 12 The alkyl group is a straight-chain alkyl group or a branched alkyl group having 4 to 12 carbon atoms.

[0010] More preferably, each R1 is independently C4 alkyl, C5 alkyl, C6 alkyl, C7 alkyl, C8 alkyl, C9 alkyl, C 10 Alkyl, C 11 Alkyl, C 12 alkyl.

[0011] More preferably, each R1 is the same alkyl group.

[0012] More preferably, R1 is selected from n-butyl (C4), tert-butyl (C4), sec-butyl (C4), isobutyl (C4), n-pentyl (C5), 3 pentyl (C5), pentyl (C5), neopentyl (C5), 3-methyl-2-butyl (C5), tert-pentyl (C5), n-hexyl (C6), n-heptyl (C7) or n-octyl (C8).

[0013] A second aspect of the present invention provides a method for preparing the Janus-type hyperbranched polyurea described in the first aspect, comprising the following steps: S1, Janus hyperbranched polyurea precursor B reacts with N-Boc-ethylenediamine to obtain an intermediate product; S2. The intermediate product undergoes a deBoc reaction in an acidic solution to obtain Janus hyperbranched polyurea precursor D. S3. The Janus hyperbranched polyurea precursor D undergoes a second reaction with 3,4-dihydroxyphenylacetic acid to obtain the Janus-type hyperbranched polyurea. The structural formulas of Janus hyperbranched polyurea precursor B and Janus hyperbranched polyurea precursor D are shown in formulas B and D, respectively:

[0014] Formula B

[0015] Formula D Among them, each R B Each independently as r B , , or ; Each R D Each independently as r D , , or ; The definitions of R1 and r1 are the same as in the first aspect of this invention; r B for ;r D for .

[0016] Preferably, in step S1, the reaction temperature of the first reaction is 110-140℃.

[0017] More preferably, the reaction temperature of the first reaction is any value or a range of any two values ​​selected from 110, 112, 114, 116, 118, 120, 122, 124, 126, 128, 130, 132, 134, 136, 138, and 140°C.

[0018] Preferably, in step S1, the reaction time of the first reaction is 36-72 h.

[0019] More preferably, the reaction time of the first reaction is any value or a range of any two values ​​among 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, and 72 h.

[0020] Preferably, in step S1, the molar ratio of Janus hyperbranched polyurea precursor B to N-Boc-ethylenediamine is 1:(4-32).

[0021] More preferably, R B for The molar ratio of Janus hyperbranched polyurea precursor B with a degree of branching of 4 to N-Boc-ethylenediamine is 1:(7-10).

[0022] Preferably, step S1 further includes the following step: after the first reaction, it is mixed with ice-cold ether and allowed to settle to obtain a precipitate.

[0023] More preferably, the precipitate is dried under vacuum at 40-60°C.

[0024] Preferably, in step S1, the first reaction is carried out in a protective atmosphere.

[0025] More preferably, the protective atmosphere is nitrogen, argon, or helium.

[0026] Preferably, in step S2, the acid in the acid solution includes at least one of trifluoroacetic acid, hydrochloric acid, formic acid, and p-toluenesulfonic acid.

[0027] More preferably, in step S2, the acid solution comprises trifluoroacetic acid and dichloromethane. Further, the volume ratio of the mixed solution of trifluoroacetic acid and dichloromethane is 1:(3~6).

[0028] Preferably, in step S2, the reaction temperature of the deBoc reaction is 15-40°C.

[0029] More preferably, the reaction temperature of the deBoc reaction is any value or a range of any two values ​​from 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39°C.

[0030] Preferably, in step S2, the reaction time for the deBoc reaction is 1.5-6 hours.

[0031] Preferably, in step S3, the reaction temperature of the second reaction is 15-40°C.

[0032] More preferably, the reaction temperature of the second reaction is any value or a range of any two values ​​from 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39°C.

[0033] Preferably, in step S3, the reaction time of the second reaction is 18-36 h.

[0034] Preferably, in step S3, the reaction time of the second reaction is any value or any combination of two values ​​from 18, 20, 22, 24, 26, 28, 30, 32, 34, and 36 hours.

[0035] Preferably, in step S3, the reaction system of the second reaction further includes a condensing agent, a catalyst, and an alkaline agent.

[0036] More preferably, the condensing agent is a carbodiimide condensing agent. For example, it can be 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl).

[0037] More preferably, the catalyst may be 1-hydroxybenzotriazole (HOBt).

[0038] More preferably, the alkaline agent may be triethylamine.

[0039] Preferably, in step S3, the second reaction is carried out in a protective atmosphere.

[0040] More preferably, the protective atmosphere is nitrogen, argon, or helium.

[0041] Preferably, step S3 further includes the following steps: after the second reaction, dialysis and drying are performed to obtain the Janus-type hyperbranched polyurea.

[0042] More preferably, the dialysis conditions are: a molecular weight cutoff of 500-1000 Da, a dialysis time of 48-96 h, and the dialysis solution is replaced every 10-14 h.

[0043] Preferably, in step S3, the molar ratio of Janus hyperbranched polyurea precursor D to 3,4-dihydroxyphenylacetic acid is 1:(4-32).

[0044] More preferably, R B for The molar ratio of Janus hyperbranched polyurea precursor D with a degree of branching of 4 to 3,4-dihydroxyphenylacetic acid is 1:(7-10).

[0045] More preferably, the dialysate used in the dialysis is pure water.

[0046] More preferably, the drying is freeze drying.

[0047] Preferably, R B For r B In this case, the Janus hyperbranched polyurea precursor B is Janus hyperbranched polyurea precursor B1; the Janus hyperbranched polyurea precursor B1 is prepared by a method including the following steps: A third reaction was carried out between quaternized hyperbranched polyurea and AB2 monomer to obtain Janus hyperbranched polyurea precursor B1 with a degree of initial branching of 2.

[0048] More preferably, the reaction temperature of the third reaction is 50-70°C.

[0049] More preferably, the reaction temperature of the third reaction is any value or any combination of two of the following: 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, and 70°C.

[0050] More preferably, the reaction time of the third reaction is 72-96 h.

[0051] More preferably, the reaction time of the third reaction is any value or a range of any two values ​​among 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, and 96 hours.

[0052] More preferably, the third reaction is carried out in a protective atmosphere.

[0053] More preferably, the molar ratio of the quaternized hyperbranched polyurea to the AB2 monomer is 1:(8~16).

[0054] More preferably, the molar ratio of the quaternized hyperbranched polyurea to the AB2 monomer is any value or a range of any two values ​​from 1:8, 1:9, 1:10, 1:11, 1:12, 1:13, 1:14, 1:15, 1:16.

[0055] Preferably, R B for In this case, the Janus hyperbranched polyurea precursor B is Janus hyperbranched polyurea precursor B2; the Janus hyperbranched polyurea precursor B2 is prepared by a method including the following steps: A third reaction was carried out between quaternized hyperbranched polyurea and AB2 monomer to obtain Janus hyperbranched polyurea precursor B1 with a degree of initial branching of 2. The Janus hyperbranched polyurea precursor B1 and 3-methylaminopropylamine are subjected to a fourth reaction to obtain the Janus hyperbranched polyurea precursor C1. The Janus hyperbranched polyurea precursor C1 is subjected to a third reaction with AB2 monomer to obtain Janus hyperbranched polyurea precursor B2 with a degree of branching at the head end of 4.

[0056] More preferably, the reaction conditions for the third reaction between the quaternized hyperbranched polyurea and the AB2 monomer are the same as those for the Janus hyperbranched polyurea precursor B1 described above.

[0057] More preferably, the reaction temperature of the fourth reaction is 110-130°C.

[0058] More preferably, the reaction temperature of the fourth reaction is any value or a range of any two values ​​among 110, 112, 114, 116, 118, 120, 122, 124, 126, 128, and 130°C.

[0059] More preferably, the reaction time of the fourth reaction is 48-72 h.

[0060] More preferably, the reaction time of the fourth reaction is any value or a range of any two values ​​among 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, and 72 hours.

[0061] More preferably, the molar ratio of the Janus hyperbranched polyurea precursor B1 to 3-methylaminopropylamine is 1:(5~8).

[0062] More preferably, the reaction temperature and reaction time of the third reaction between the Janus hyperbranched polyurea precursor C1 and the AB2 monomer are the same as the third reaction conditions of the aforementioned quaternized hyperbranched polyurea and the AB2 monomer.

[0063] More preferably, the molar ratio of the Janus hyperbranched polyurea precursor C1 to the AB2 monomer is 1:(14~20).

[0064] More preferably, the molar ratio of the Janus hyperbranched polyurea precursor C1 to the AB2 monomer is any value or a range of any two values ​​from 1:14, 1:15, 1:16, 1:17, 1:18, 1:19, and 1:20.

[0065] Preferably, R B for In this case, the Janus hyperbranched polyurea precursor B is Janus hyperbranched polyurea precursor B3; the Janus hyperbranched polyurea precursor B3 is prepared by a method including the following steps: A third reaction was carried out between quaternized hyperbranched polyurea and AB2 monomer to obtain Janus hyperbranched polyurea precursor B1 with a degree of initial branching of 2. The Janus hyperbranched polyurea precursor B1 and 3-methylaminopropylamine are subjected to a fourth reaction to obtain the Janus hyperbranched polyurea precursor C1. The Janus hyperbranched polyurea precursor C1 is subjected to a third reaction with AB2 monomer to obtain Janus hyperbranched polyurea precursor B2 with a degree of branching at the first end of 4. The Janus hyperbranched polyurea precursor B2 and 3-methylaminopropylamine were subjected to a fourth reaction to obtain the Janus hyperbranched polyurea precursor C2. The Janus hyperbranched polyurea precursor C2 is subjected to a third reaction with AB2 monomer to obtain Janus hyperbranched polyurea precursor B3 with a degree of branching at the head end of 8.

[0066] More preferably, the preparation methods of Janus hyperbranched polyurea precursor B1, Janus hyperbranched polyurea precursor C1 and Janus hyperbranched polyurea precursor B2 are the same as those of Janus hyperbranched polyurea precursor B2.

[0067] More preferably, the reaction temperature and reaction time of the fourth reaction between the Janus hyperbranched polyurea precursor B2 and 3-methylaminopropylamine are the same as those of the fourth reaction between the Janus hyperbranched polyurea precursor B1 and 3-methylaminopropylamine described above.

[0068] More preferably, the reaction temperature and reaction time of the third reaction between the Janus hyperbranched polyurea precursor C2 and the AB2 monomer are the same as the third reaction conditions of the aforementioned quaternized hyperbranched polyurea and the AB2 monomer.

[0069] Preferably, R B for In this case, the Janus hyperbranched polyurea precursor B is Janus hyperbranched polyurea precursor B4; the Janus hyperbranched polyurea precursor B4 is prepared by a method including the following steps: A third reaction was carried out between quaternized hyperbranched polyurea and AB2 monomer to obtain Janus hyperbranched polyurea precursor B1 with a degree of initial branching of 2. The Janus hyperbranched polyurea precursor B1 and 3-methylaminopropylamine are subjected to a fourth reaction to obtain the Janus hyperbranched polyurea precursor C1. The Janus hyperbranched polyurea precursor C1 is subjected to a third reaction with AB2 monomer to obtain Janus hyperbranched polyurea precursor B2 with a degree of branching at the first end of 4. The Janus hyperbranched polyurea precursor B2 and 3-methylaminopropylamine were subjected to a fourth reaction to obtain the Janus hyperbranched polyurea precursor C2. The Janus hyperbranched polyurea precursor C2 is subjected to a third reaction with AB2 monomer to obtain Janus hyperbranched polyurea precursor B3 with a first-terminal branching degree of 8. The Janus hyperbranched polyurea precursor B3 and 3-methylaminopropylamine were subjected to a fourth reaction to obtain the Janus hyperbranched polyurea precursor C3. The Janus hyperbranched polyurea precursor C3 is subjected to a third reaction with AB2 monomer to obtain Janus hyperbranched polyurea precursor B4 with a degree of branching at the head end of 16.

[0070] More preferably, the preparation methods of Janus hyperbranched polyurea precursor B1, Janus hyperbranched polyurea precursor C1, Janus hyperbranched polyurea precursor B2, Janus hyperbranched polyurea precursor C2, and Janus hyperbranched polyurea precursor B3 are the same as those of Janus hyperbranched polyurea precursor B3.

[0071] More preferably, the reaction temperature and reaction time of the fourth reaction between the Janus hyperbranched polyurea precursor B3 and 3-methylaminopropylamine are the same as those of the fourth reaction between the Janus hyperbranched polyurea precursor B1 and 3-methylaminopropylamine described above.

[0072] More preferably, the reaction temperature and reaction time of the third reaction between the Janus hyperbranched polyurea precursor C3 and the AB2 monomer are the same as the third reaction conditions of the aforementioned quaternized hyperbranched polyurea and the AB2 monomer.

[0073] This invention provides a method for preparing Janus hyperbranched polyurea precursors B1-B4. Starting from the first end of a quaternary ammonium hyperbranched polyurea (QA-BPU), a branched structure is constructed on the other side. An AB2 monomer containing double bonds is pre-synthesized. The QA-BPU with a secondary amine at the first end undergoes a Michael addition reaction with the AB2 monomer, thereby increasing the number of reaction sites at the first end from 1 to 2, yielding a first-generation product. By modifying the end with secondary amination, a second-generation product with a branching degree of 4 is obtained by reacting with the AB2 monomer. By changing the number of synthesis cycles (iterations), branched structures with different degrees of branching can be designed, ultimately yielding functional products with tunable performance.

[0074] The structural formulas of the quaternized hyperbranched polyurea and the Janus hyperbranched polyurea precursor C1 are shown in Formula A and Formula C1, respectively:

[0075] Formula A

[0076] Formula C1 The structural formula of the AB2 monomer is shown below: .

[0077] More preferably, the quaternized hyperbranched polyurea is prepared by a method including the following steps: reacting hyperbranched polyurea with a quaternary ammonium salt in a fifth reaction to obtain the quaternized hyperbranched polyurea; The structural formula of the quaternary ammonium salt is: .

[0078] More preferably, the temperature of the fifth reaction is 120-130°C.

[0079] More preferably, the fifth reaction takes 48-72 hours.

[0080] More preferably, the quaternary ammonium salt is prepared by a method comprising the following steps: 3-Dimethylaminopropylamine and ditert-butyl dicarbonate were dissolved in a mixed solution of tetrahydrofuran and sodium hydroxide, reacted, and the organic layer was collected after washing. The upper aqueous layer was discarded and dried to obtain tert-butyl(3-(dimethylamino)propyl)carbamate. The tert-butyl (3-(dimethylamino)propyl)carbamate and bromoalkane were dissolved in anhydrous ethanol. After deoxygenation reaction, the reactants were precipitated in n-hexane to obtain a precipitate, which was dried to obtain 3-(tert-butoxycarbonyl)amino-N,N-dimethyl-N-alkylpropane-1-ammonium bromide. Dissolve 3-(tert-butoxycarbonyl)amino-N,N-dimethyl-N-alkylpropane-1-ammonium bromide in a mixed solution of hydrochloric acid and methanol, react, remove the solvent, and dry to obtain the quaternary ammonium salt.

[0081] More preferably, the bromoalkane is a bromoalkane containing 4-12 carbon atoms.

[0082] A third aspect of the present invention provides the use of the Janus-type hyperbranched polyurea described in the first aspect in any of the following: a) Antibacterial; b) Prepare antibacterial products; c) Inhibit or eliminate bacterial biofilm formation; d) Prepare products that inhibit or eliminate bacterial biofilm formation; e) Prepare products for the prevention and / or treatment of diseases caused by bacterial infections; The application described is for purposes other than disease treatment.

[0083] Preferably, the bacteria include Staphylococcus, Streptococcus, Enterococcus, Enterobacteriaceae, or Pseudomonas.

[0084] More preferably, the bacteria include one or more of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Streptococcus mutans, and Enterococcus faecalis.

[0085] Preferably, the product includes a drug, reagent, or additive.

[0086] The beneficial effects of this invention are: This invention provides a Janus-type hyperbranched polyurea. Through molecular design, an asymmetric spatial distribution of chemical composition is achieved within the hyperbranched polyurea system, with two clearly defined functional zones: an antibacterial quaternary ammonium group on one side and an adhesive catechol group on the other. Simultaneously, the Janus hyperbranched structure allows for the partitioning of functional groups within the material, thereby enabling efficient functioning. Therefore, the Janus antibacterial hyperbranched polyurea of ​​this invention can be used to modify various biomaterials (metals, ceramics, synthetic polymers) to prepare antibacterial surfaces through immersion methods or other methods. It exhibits broad-spectrum antibacterial properties, covering a wide range of Gram-positive and Gram-negative bacteria, and has broad potential for clinical applications.

[0087] This invention provides a method for preparing the above-mentioned Janus-type hyperbranched polyurea, which simultaneously modifies the functional molecules with catechol groups, giving them adhesive properties and greatly facilitating subsequent surface modification of the materials. Attached Figure Description

[0088] Figure 1 The 1H NMR spectrum is for quaternized hyperbranched polyurea.

[0089] Figure 2 The 1H NMR spectrum of catechol-modified multifunctional Janus antibacterial hyperbranched polyurea.

[0090] Figure 3 These are photos of samples (titanium, stainless steel, ceramic, TPU, PDMS, PET) before and after modification with multifunctional Janus antibacterial hyperbranched polyurea, taken during contact angle testing.

[0091] Figure 4 The specific results of contact angle tests are shown for samples of the multifunctional Janus antibacterial hyperbranched polyurea before and after modification.

[0092] Figure 5 X-ray photoelectron spectroscopy (XPS) of different substrate surfaces before and after Janus antibacterial hyperbranched polyurea modification; where a is titanium substrate, b is stainless steel, c is ceramic, d is PDMS, e is PET, and f is TPU.

[0093] Figure 6 The X-ray photoelectron spectroscopy (XPS) spectra of titanium and ceramic substrates before and after Janus antibacterial hyperbranched polyurea modification are shown.

[0094] Figure 7 Experimental characterization of the bactericidal properties of the surface of the multifunctional Janus antibacterial hyperbranched polyurea modified sample.

[0095] Figure 8 Results of the bactericidal performance of Janus antibacterial hyperbranched polyurea modified sample surface against Escherichia coli.

[0096] Figure 9 Results of the bactericidal performance of Janus antibacterial hyperbranched polyurea modified sample surface against Staphylococcus aureus.

[0097] Figure 10 Blood compatibility of the surface of multifunctional Janus antibacterial hyperbranched polyurea modified sample.

[0098] Figure 11 Cytotoxicity assessment of the surface of multifunctional Janus antibacterial hyperbranched polyurea modified samples. Detailed Implementation

[0099] The present invention will be further described in detail below through specific embodiments. Unless otherwise specified, the raw materials used in the following embodiments can be obtained from conventional commercial channels or prepared and isolated through simple synthesis; unless otherwise specified, the processes employed are conventional processes in the art.

[0100] Example 1 This embodiment provides a catechol-modified Janus antibacterial hyperbranched polyurea, the preparation method of which is as follows: (1) The specific synthesis of hyperbranched polyurea adopts an existing process (patent CN116987296A), and the specific steps are as follows: Synthetic routes such as Figure 1 As shown, bis(hexamethylenetriamine) (10 g, 46 mmol) and carbonylbiscaprolactam (24 g, 94 mmol) were dissolved in 200 mL of dry N,N Argon gas was bubbled through dimethylformamide for 30 min to remove dissolved O2, followed by reaction at 80 °C for 16 h under argon protection. After removing most of the solvent by vacuum distillation, the residue was dried under vacuum at 50 °C for 16 h to obtain crude AB2 monomer for synthesizing hyperbranched polyurea. Subsequently, the crude AB2 was subjected to column chromatography using a mixed solvent containing ethyl acetate and petroleum ether (volume ratio 3:1) to remove residual trace impurities.

[0101] Dissolve 5.0 g of AB2 monomer in 30 mL of dry N,N The monomer solution was reacted in dimethylformamide solvent, and then argon gas was continuously bubbled into it for 30 min to remove dissolved oxygen. The monomer solution was stirred at 145 °C for 8 h to allow self-polymerization. After the reaction was completed, the reaction solution was cooled at room temperature and precipitated in ice-cold diethyl ether to obtain a precipitate. The precipitate was collected and vacuum dried at 50 °C for 16 h to obtain hyperbranched polyurea.

[0102] (2) The synthetic route and specific preparation steps of quaternary ammonium salts are as follows:

[0103] 10 mmol of 3-dimethylaminopropylamine and 15 mmol of ditert-butyl dicarbonate were dissolved in 260 mL of a mixed solution of tetrahydrofuran and sodium hydroxide (volume ratio 5:8), and the mixture was stirred at room temperature for 14 h. After the reaction was complete, tetrahydrofuran was removed by vacuum distillation, then dichloromethane was added, the upper aqueous layer was discarded, and the mixture was washed three times with sodium bicarbonate solution. The organic phase was collected and dried over anhydrous magnesium sulfate. Finally, the solvent was removed by vacuum distillation, and the mixture was dried under vacuum at 50 °C for 16 h to obtain tert-butyl(3-(dimethylamino)propyl)carbamate.

[0104] 7 mmol of tert-butyl(3-(dimethylamino)propyl)carbamate and 14 mmol of 1-bromooctane were dissolved in 60 mL of anhydrous ethanol. Argon gas was bubbled through the solution for 30 min to remove dissolved O2. The reaction was then carried out at 75 °C for 4 h under argon protection. After the reaction was completed, most of the solvent was removed by rotary evaporation under reduced pressure. The precipitate was then settled three times with n-hexane and collected. The precipitate was dried under vacuum at 50 °C for 16 h to obtain 3-(tert-butoxycarbonyl)amino-N,N-dimethyl-N-octylpropane-1-ammonium bromide.

[0105] Dissolve 5g of the above product in 20mL of a mixed solution of hydrochloric acid and methanol (volume ratio of 1:4), stir at room temperature for 3h, remove most of the solvent by vacuum distillation, and dry under vacuum at 50℃ for 16h to obtain the quaternary ammonium salt.

[0106] (3) The synthetic route and specific preparation steps of quaternized hyperbranched polyurea are as follows:

[0107]

[0108] Dissolve hyperbranched polyurea (1 mmol), quaternary ammonium salt (15 mmol), and triethylamine (15 mmol) in 30 mL of N,N Dimethylformamide was purged with argon gas for 30 minutes to remove oxygen, then the reaction system was heated to 125°C and stirred continuously for 48 hours. After the reaction was complete, most of the organic solvent was removed by rotary evaporation, and the sample was placed in a dialysis bag (1000 Da) for dialyzing. The dialysate (pure water) was changed every 12 hours for a total of 4 days. Finally, the sample in the dialysis bag was collected, freeze-dried, and ready for use.

[0109] (4) The synthetic route and specific preparation steps of Janus hyperbranched polyurea are as follows:

[0110]

[0111] 1 mmol of quaternized hyperbranched polyurea and 10 mmol of AB2 monomer were dissolved in 30 mL of N,N-dimethylformamide. After removing oxygen by purging with argon gas for 30 min, the reaction system was heated to 60 °C and stirred continuously for 72 h. The precipitate was settled in diethyl ether / dichloromethane (1:2) and dried under vacuum at 50 °C for 16 h to obtain quaternized hyperbranched polyurea with a degree of branching at the head end of 2.

[0112] The above product (0.8 mmol) and 3-methylaminopropylamine (4.8 mmol) were dissolved in 30 mL of N,N-dimethylformamide. After removing oxygen by purging with argon for 30 min, the reaction system was heated to 125 °C and stirred continuously for 48 h. The precipitate was precipitated in ice-cold diethyl ether and dried under vacuum at 50 °C for 16 h to obtain secondary amination-modified quaternized hyperbranched polyurea. The above product (0.8 mmol) and AB2 monomer (12.8 mmol) were dissolved in 40 mL of N,N-dimethylformamide. After removing oxygen by purging with argon for 30 min, the reaction system was heated to 60 °C and stirred continuously for 72 h. The precipitate was precipitated in diethyl ether / dichloromethane (1:2) and dried under vacuum at 50 °C for 16 h to obtain Janus hyperbranched polyurea with a degree of branching at the head end of 4.

[0113] (5) The synthetic route and specific preparation steps of catechol-modified Janus quaternized hyperbranched polyurea are as follows:

[0114] 0.8 mmol of quaternized hyperbranched polyurea with a branching degree of 4 and 6.4 mmol of mono-Boc ethylenediamine were dissolved in 30 mL of N,N-dimethylformamide. After removing oxygen by purging with argon for 30 min, the reaction system was heated to 125 °C and stirred continuously for 48 h. The precipitate was settled in ice-cold diethyl ether and dried under vacuum at 50 °C for 16 h to obtain Boc-modified quaternized hyperbranched polyurea.

[0115] The above product was dissolved in 20 mL of a mixed solution of trifluoroacetic acid and dichloromethane (volume ratio of 1:4), and the mixture was stirred at room temperature for 3 h. Most of the solvent was removed by vacuum distillation, and the product was dried under vacuum at 50 °C for 16 h to obtain the primary amine-modified quaternized hyperbranched polyurea.

[0116] The above product (0.6 mmol), 3,4-dihydroxyphenylacetic acid (4.8 mmol), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (4.8 mmol), 1-hydroxybenzotriazole (4.8 mmol), and triethylamine (7.2 mol) were dissolved in 50 mL of N,N-dimethylformamide. After removing oxygen by purging with argon gas for 30 min, the mixture was stirred at room temperature for 24 h. After the reaction was completed, most of the organic solvent was removed by rotary evaporation. The mixture was then dialyzed in a dialysis bag (1000 Da), with the dialysate (pure water) replaced every 12 h for a total of 3 days, yielding catechol-modified multifunctional Janus antibacterial hyperbranched polyurea. Finally, the sample in the dialysis bag was collected, freeze-dried, and ready for use.

[0117] The quaternized hyperbranched polyurea and the catechol-modified multifunctional Janus antibacterial hyperbranched polyurea prepared above were characterized by 1H NMR spectroscopy, such as... Figure 1 and Figure 2 As shown in the spectrum, the synthesized product has the correct structure.

[0118] Experimental characterization of catechol-modified Janus antibacterial hyperbranched polyurea (JBPU) 1. Experimental characterization of antibacterial surface modification The catechol-modified Janus antibacterial hyperbranched polyurea was dissolved in Tris-HCl buffer (pH=8.5) to prepare a coating solution with a concentration of 50 mg / mL. Titanium sheets, stainless steel sheets, ceramic sheets, polydimethylsiloxane (PDMS) sheets, thermoplastic polyurethane (TPU) sheets, and polyethylene terephthalate (PET) sheets (all 10 mm × 10 mm) were immersed in the coating solution and allowed to stand for two days. The modified samples were then removed, rinsed three times with pure water, and allowed to air dry before use.

[0119] Static contact angle tests were conducted on titanium sheets, stainless steel sheets, ceramic sheets, PDMS sheets, TPU sheets, and PET sheets before and after antibacterial modification. The results are as follows: Figure 3-4 As shown, the antibacterial groups of Janus antibacterial hyperbranched polyurea are highly hydrophilic. After antibacterial modification of the substrate, the hydrophilicity of all substrate surfaces was significantly improved, which indicates the success of the antibacterial modification of multifunctional Janus hyperbranched polyurea.

[0120] To further verify the successful immobilization of Janus antibacterial hyperbranched polyurea on different substrate surfaces, X-ray photoelectron spectroscopy (XPS) analysis was performed on samples before and after modification. The results are as follows: Figure 5-6 As shown, obvious N 1s characteristic peaks were detected on the surfaces of all modified substrates. Characteristic peaks appeared at approximately 399.5 eV and 402.5 eV in the high-resolution N 1s spectra, which are attributed to the NC / NH structure in the polyurea backbone and the quaternary ammonium nitrogen (N) salt. +The structure demonstrates that Janus antibacterial hyperbranched polyurea has been successfully introduced into the substrate surface while retaining its antibacterial functional groups. Combined with contact angle test results and XPS analysis, it is evident that Janus antibacterial hyperbranched polyurea can achieve stable modification on the surfaces of various materials such as metals, ceramics, and polymers, and significantly improve their surface hydrophilicity, verifying the good versatility of this antibacterial modification strategy.

[0121] Culture Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), then dilute with PBS to prepare a 10⁻⁶ solution. 5 CFU / mL bacterial suspension. 20 μL of bacterial suspension was added to the surfaces of antibacterial modified titanium, stainless steel, ceramic, PDMS, TPU, and PET sheets, respectively, and incubated at 37°C for 2 h. The samples were then placed in EP tubes containing 2 mL PBS, sonicated for 5 min, and 100 μL was spread onto agar plates and incubated at 37°C for 18 h before photographing and counting. Results are as follows: Figure 7-9 As shown, regardless of whether the experimental bacteria were Gram-negative or Gram-positive, the bactericidal rate was close to 100%, and all antibacterial surfaces exhibited good bactericidal performance.

[0122] 2. Evaluation of blood compatibility and cytotoxicity of catechol-modified Janus antibacterial hyperbranched polyurea (JBPU) surface.

[0123] (1) Blood compatibility: Take 2 mL of fresh whole blood and centrifuge at 1000 rpm for 5 min to separate red blood cells. Wash the red blood cells 3 times with PBS until the supernatant no longer shows redness, and add 10 mL of PBS to obtain a red blood cell suspension. Add 1.5 mL of red blood cell suspension to an EP tube, and then put titanium sheets, antibacterial titanium sheets (preparation method as above), polylactic acid (PLA) sheets, and antibacterial PLA sheets (preparation method as per TPU sheets) into the EP tube. Among them, the blank group is the negative control group, and the 0.1% Triton group is the positive control group. After incubating at 37 ℃ for 2 h, each group is centrifuged at 1000 rpm for 5 min, and the supernatant of each group is collected. The optical density (OD) at 540 nm is measured by an ELISA reader to calculate the hemolysis rate.

[0124] Blood test results as follows Figure 10 As shown, both the antibacterial titanium sheet surface and the antibacterial PLA surface exhibit good blood compatibility compared to the negative control group and the positive control group.

[0125] (2) Cytotoxicity: 200 μL of bone marrow mesenchymal stem cells (BMSCs, density 1.1 × 10⁻⁶) were injected. 5A suspension of (cell / mL) was added dropwise to titanium and antibacterial titanium sheets in 24-well plates and incubated in a cell culture incubator for 3 h. Then, 2 mL of DMEM high-glucose medium containing 10% (v / v) fetal bovine serum and 1% (v / v) streptomycin-penicillin (PS) antibiotic solution was added to each well and incubated in a cell culture incubator (37 ℃, 5% CO2). Cell viability was assessed on days 1, 2, and 3. To assess cell viability, 800 μL of CCK-8 working solution (prepared by adding 1 mL of CCK-8 solution to 10 mL of fresh medium) was added to each well, and the plates were incubated in a 37 ℃ cell culture incubator for 0.5 h. Finally, the OD value of the solution at 450 nm was measured to calculate cell viability.

[0126] The cytotoxicity of BMSC cells to antibacterial surfaces was evaluated using the CCK-8 assay. Figure 11 As shown, cells are able to proliferate normally on the antibacterial surface. These results indicate that the Janus antibacterial hyperbranched polyurea surface exhibits good cell compatibility and low cytotoxicity.

[0127] The above description represents the preferred embodiments of the present invention. It should be noted that those skilled in the art can make various improvements and modifications without departing from the principles of the present invention, and these improvements and modifications are also considered to be within the scope of protection of the present invention.

Claims

1. A Janus-type hyperbranched polyurea, characterized in that, The structural formula of the Janus-type hyperbranched polyurea is shown in Formula I: Formula I Each R is independently represented by r2, , or ; r1 is r2 is ; The connection point is indicated by ⊕; the positive charge symbol is indicated by ⊕; each R1 is independently C4-C. 12 Alkyl groups.

2. The method for preparing Janus-type hyperbranched polyurea according to claim 1, characterized in that, Includes the following steps: S1, Janus hyperbranched polyurea precursor B reacts with N-Boc-ethylenediamine to obtain an intermediate product; S2. The intermediate product undergoes a deBoc reaction in an acidic solution to obtain Janus hyperbranched polyurea precursor D. S3. The Janus hyperbranched polyurea precursor D undergoes a second reaction with 3,4-dihydroxyphenylacetic acid to obtain the Janus-type hyperbranched polyurea. The structural formulas of Janus hyperbranched polyurea precursor B and Janus hyperbranched polyurea precursor D are shown in formulas B and D, respectively: Formula B Formula D Among them, each R B Each independently as r B , , or ; Each R D Each independently as r D , , or ; R1 and r1 are defined as in claim 1; r B for ;r D for .

3. The method for preparing Janus-type hyperbranched polyurea according to claim 2, characterized in that, In step S1, the reaction temperature of the first reaction is 110-140℃; And / or, the reaction time of the first reaction is 36-72 h.

4. The method for preparing Janus-type hyperbranched polyurea according to claim 2, characterized in that, In step S3, the reaction temperature of the second reaction is 15-40℃; And / or, the reaction time of the second reaction is 18-36 h.

5. The method for preparing Janus-type hyperbranched polyurea according to claim 2, characterized in that, R B For r B In this case, the Janus hyperbranched polyurea precursor B is Janus hyperbranched polyurea precursor B1; the Janus hyperbranched polyurea precursor B1 is prepared by a method including the following steps: A third reaction was carried out between quaternized hyperbranched polyurea and AB2 monomer to obtain Janus hyperbranched polyurea precursor B1 with a degree of initial branching of 2. Or, R B for In this case, the Janus hyperbranched polyurea precursor B is Janus hyperbranched polyurea precursor B2; the Janus hyperbranched polyurea precursor B2 is prepared by a method including the following steps: A third reaction was carried out between quaternized hyperbranched polyurea and AB2 monomer to obtain Janus hyperbranched polyurea precursor B1 with a degree of initial branching of 2. The Janus hyperbranched polyurea precursor B1 and 3-methylaminopropylamine are subjected to a fourth reaction to obtain the Janus hyperbranched polyurea precursor C1. The Janus hyperbranched polyurea precursor C1 is subjected to a third reaction with AB2 monomer to obtain Janus hyperbranched polyurea precursor B2 with a degree of branching at the first end of 4. Or, R B for In this case, the Janus hyperbranched polyurea precursor B is Janus hyperbranched polyurea precursor B3; the Janus hyperbranched polyurea precursor B3 is prepared by a method including the following steps: A third reaction was carried out between quaternized hyperbranched polyurea and AB2 monomer to obtain Janus hyperbranched polyurea precursor B1 with a degree of initial branching of 2. The Janus hyperbranched polyurea precursor B1 and 3-methylaminopropylamine are subjected to a fourth reaction to obtain the Janus hyperbranched polyurea precursor C1. The Janus hyperbranched polyurea precursor C1 is subjected to a third reaction with AB2 monomer to obtain Janus hyperbranched polyurea precursor B2 with a degree of branching at the first end of 4. The Janus hyperbranched polyurea precursor B2 and 3-methylaminopropylamine were subjected to a fourth reaction to obtain the Janus hyperbranched polyurea precursor C2. The Janus hyperbranched polyurea precursor C2 is subjected to a third reaction with AB2 monomer to obtain Janus hyperbranched polyurea precursor B3 with a first-terminal branching degree of 8. Or, R B for In this case, the Janus hyperbranched polyurea precursor B is Janus hyperbranched polyurea precursor B4; the Janus hyperbranched polyurea precursor B4 is prepared by a method including the following steps: A third reaction was carried out between quaternized hyperbranched polyurea and AB2 monomer to obtain Janus hyperbranched polyurea precursor B1 with a degree of initial branching of 2. The Janus hyperbranched polyurea precursor B1 and 3-methylaminopropylamine are subjected to a fourth reaction to obtain the Janus hyperbranched polyurea precursor C1. The Janus hyperbranched polyurea precursor C1 is subjected to a third reaction with AB2 monomer to obtain Janus hyperbranched polyurea precursor B2 with a degree of branching at the first end of 4. The Janus hyperbranched polyurea precursor B2 and 3-methylaminopropylamine were subjected to a fourth reaction to obtain the Janus hyperbranched polyurea precursor C2. The Janus hyperbranched polyurea precursor C2 is subjected to a third reaction with AB2 monomer to obtain Janus hyperbranched polyurea precursor B3 with a first-terminal branching degree of 8. The Janus hyperbranched polyurea precursor B3 and 3-methylaminopropylamine were subjected to a fourth reaction to obtain the Janus hyperbranched polyurea precursor C3. The Janus hyperbranched polyurea precursor C3 is subjected to a third reaction with AB2 monomer to obtain Janus hyperbranched polyurea precursor B4 with a first-terminal branching degree of 16. The structural formulas of the quaternized hyperbranched polyurea and the Janus hyperbranched polyurea precursor C1 are shown in Formula A and Formula C1, respectively: Formula A Formula C1 The structural formula of the AB2 monomer is shown below: 。 6. The method for preparing Janus-type hyperbranched polyurea according to claim 5, characterized in that, The reaction temperature of the third reaction is 50-70℃; And / or, the reaction time of the third reaction is 72-96 h.

7. The method for preparing Janus-type hyperbranched polyurea according to claim 5, characterized in that, The reaction temperature of the fourth reaction is 110-130℃; And / or, the reaction time of the fourth reaction is 48-72 h.

8. The method for preparing Janus-type hyperbranched polyurea according to claim 5, characterized in that, The quaternized hyperbranched polyurea is prepared by a method including the following steps: reacting hyperbranched polyurea with a quaternary ammonium salt in a fifth reaction to obtain the quaternized hyperbranched polyurea; The structural formula of the quaternary ammonium salt is: .

9. The use of the Janus-type hyperbranched polyurea according to claim 1 in any of the following: a) Antibacterial; b) Inhibit or eliminate bacterial biofilm formation; c) Preparation of antibacterial products; d) Prepare products that inhibit or eliminate bacterial biofilm formation; The application described is for purposes other than disease treatment.

10. The application according to claim 9, characterized in that, The bacteria include Staphylococcus, Streptococcus, Enterococcus, Enterobacteriaceae, or Pseudomonas.

11. The use of the Janus-type hyperbranched polyurea of ​​claim 1 in the preparation of products for the prevention and / or treatment of diseases caused by bacterial infections.

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