A kind of urea sulfobetaine zwitterion hydrogel and preparation method thereof

Abstract

The invention discloses a urea-based sulfobetaine zwitterionic hydrogel and a preparation method thereof, firstly reacting urea-based groups with ammonia monomers containing tertiary amino groups by isocyanoethyl (methyl) acrylate, thereby obtaining a vinyl intermediate containing urea-based groups and tertiary amino groups, further reacting with 1,3-propane sultone to obtain urea-based sulfobetaine zwitterionic monomers, and finally preparing urea-based sulfobetaine zwitterionic hydrogels by free radical-induced double bond polymerization. Due to the introduction of multiple hydrogen bonds and electrostatic interactions between sulfonic acid groups, the hydrogel can be gelled without a crosslinking agent, and the gel has excellent mechanical properties. Due to the strong hydration of small molecule crosslinking agents and zwitterionic parts not being introduced, the hydrogel also has good biocompatibility and excellent antifouling properties. The hydrogel is made to have potential application prospects in biological fields such as wound dressings, drug packaging, and postoperative anti-adhesion.

Description

Technical Field

[0001] The invention belongs to the field of hydrogel materials, and more specifically, relates to a urea sulfobetaine zwitterionic hydrogel and a preparation method thereof. Background Art

[0002] The adhesion of non-specific proteins, cells, bacteria, etc. has brought serious obstacles to the sustainable development of hydrogels in the biomedical field. Zwitterionic hydrogels contain strongly charged groups and high dipole moments on their molecular chains. Zwitterionic groups can firmly bind to water molecules through electrostatically induced hydration, thereby forming a dense hydration layer on the surface of the material. This hydration layer can effectively inhibit the adsorption of non-specific proteins, cells, bacteria, etc., and show excellent biocompatibility and antifouling properties. Therefore, zwitterionic hydrogels have great application prospects in the biomedical field. For example, it can prevent biological contamination of medical materials and effectively inhibit immunogenic reactions as implantable materials. However, most of the existing zwitterionic polymer hydrogels need to be cross-linked using chemical cross-linking agents, so toxic small molecules are inevitably introduced, thereby reducing the biocompatibility of zwitterionic hydrogels. The present invention generates urea groups by reacting (methyl) acrylate isocyanoethyl with ammonia containing tertiary amino groups, obtains a vinyl intermediate containing urea groups and tertiary amino groups, then realizes zwitterionization through ring opening of 1,3-propane sultone to obtain urea sulfobetaine zwitterion monomers, and finally prepares urea sulfobetaine zwitterion hydrogel through free radical-initiated double bond polymerization. Due to the electrostatic interaction between multiple hydrogen bonds and sulfonic acid groups in the gel, the hydrogel can be gelled without a crosslinking agent, and the gel has excellent mechanical properties. Since the gel does not introduce a small molecule crosslinking agent and the strong hydration of the zwitterion part, the hydrogel also has good biocompatibility and excellent antifouling properties. It shows great application prospects in the biological field. Summary of the invention

[0003] The purpose of the present invention is to provide a urea sulfobetaine zwitterionic hydrogel and a preparation method thereof, wherein the crosslinking effect of a small molecule crosslinking agent is replaced by the force of hydrogen bonds between polymer molecules and the electrostatic interaction of zwitterionic parts, so that the hydrogel can be gelled without adding any crosslinking agent, and the gel has excellent mechanical properties. The problem that traditional hydrogels need to add additional crosslinking agents to gel and the mechanical properties of traditional zwitterionic hydrogels are usually weak is overcome, and the biocompatibility of zwitterionic hydrogels is improved.

[0004] The technical purpose of the present invention is achieved through the following technical solutions.

[0005] A urea sulfobetaine zwitterion hydrogel is characterized in that a urea sulfobetaine zwitterion monomer is dissolved in water or a phosphate buffer solution to prepare a solution with a molar concentration of 1 to 6 mol / L, and then a photoinitiator or a thermal initiator is added in an amount of 0.1 to 2% relative to the molar ratio of the monomer, and then injected into a closed mold, and the monomer polymerization is initiated by photoinitiation or thermal initiation. After a period of time, the mold is removed and the solution is immersed in water for at least 1 day to remove unreacted monomers, so as to obtain the urea sulfobetaine zwitterion hydrogel.

[0006] The molecular structure of the polymer is shown below:

[0007]

[0008] Wherein, R is CH3 or H; m is the degree of polymerization of the zwitterionic monomer, which is 20 to 5000; n is 1;

[0009] The above-mentioned 2-hydroxy-2-methyl-1-phenyl-1-propanone (photoinitiator 1173) or 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone (photoinitiator 2959) or ammonium persulfate is selected as the photoinitiator or thermal initiator.

[0010] When 2-hydroxy-2-methyl-1-phenyl-1-propanone (photoinitiator 1173) or 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone (photoinitiator 2959) is selected as the initiator for crosslinking, it is placed in an ultraviolet light crosslinker to initiate monomer polymerization, and the reaction time is 10 to 180 minutes. When ammonium persulfate is selected as a thermal initiator, it is placed in an oven for heating to initiate monomer polymerization, the polymerization reaction temperature is 60-80° C., and the polymerization time is 12 hours.

[0011] The synthesis method of the above-mentioned urea sulfobetaine zwitterion monomer is as follows:

[0012] Step 1: react (meth) acrylic acid isocyanate and an ammonia monomer containing a tertiary amino group to generate a urea group to obtain a vinyl intermediate containing a urea group and a tertiary amino group. Weigh (meth) acrylic acid isocyanoethyl and an ammonia monomer containing a tertiary amino group in a molar ratio of 1: (0.5-2) respectively and dissolve them in anhydrous tetrahydrofuran or anhydrous acetone. Add the (meth) acrylic acid isocyanoethyl solution dropwise to the ammonia monomer solution containing a tertiary amino group at 0-10°C with stirring, and react at 0-10°C for 12 hours under nitrogen protection. The solution after the reaction is evaporated by a low-temperature rotary evaporator to remove the solvent to obtain a vinyl intermediate containing a tertiary amino group and a urea group. Its structure is shown below:

[0013]

[0014] Wherein, R is CH3 or H; n is 1.

[0015] The structure of isocyanoethyl (meth)acrylate is shown below:

[0016]

[0017] Wherein, R is CH3 or H.

[0018] The structure of the above-mentioned amino monomer containing tertiary amine group is shown below:

[0019]

[0020] Where n is 1.

[0021] Step 2: The vinyl intermediate containing urea and tertiary amino groups obtained in step 1 is subjected to a ring-opening reaction with 1,3-propane sultone to obtain a urea-based sulfobetaine zwitterionic monomer. The intermediate obtained in step 1 is weighed in a molar ratio of 1: (1-2) and dissolved in 25 ml of anhydrous tetrahydrofuran or anhydrous acetone. Then 1-2 equivalents of 1,3-propane sultone are weighed and added dropwise to the intermediate solution, stirring while adding dropwise. After the addition is complete, the dropping funnel is rinsed with 200 microliters of anhydrous tetrahydrofuran or anhydrous acetone, and the reaction is stirred at 45-60°C for 12 hours. The white precipitate is obtained by precipitation with ether and centrifugation, and the urea-based sulfobetaine zwitterionic monomer is obtained after drying in a vacuum drying oven. Its structure is shown below:

[0022]

[0023] Wherein, R is CH3 or H; n is 1.

[0024] Compared with the prior art, the present invention obtains a vinyl intermediate containing a tertiary amine group and a urea group by reacting an isocyanate with an ammonia containing a tertiary amine, and further reacts with 1,3-propane sultone to obtain a urea-based sulfobetaine zwitterionic monomer. Then, a self-healing and injectable zwitterionic hydrogel is prepared by free radical polymerization without adding any crosslinking agent. The crosslinking effect of the small molecule crosslinking agent is replaced by the force of hydrogen bonds between polymer molecules, so that the hydrogel can also be gelled without adding any crosslinking agent, and due to the internal hydrogen bond supramolecular effect and the electrostatic interaction of the zwitterionic part, it also has excellent mechanical properties. The problem that traditional hydrogels need to add additional crosslinking agents to gel and that traditional zwitterionic hydrogels usually have weak mechanical properties is overcome, and the biocompatibility of zwitterionic hydrogels is improved, so that the hydrogel has potential application prospects in biological fields such as wound dressings, drug encapsulation, and postoperative anti-adhesion.

[0025] The advantages of the present invention are: (1) the raw materials are easily available, and the synthesis and preparation methods are simple; (2) the prepared zwitterionic hydrogel can be gelled without adding any cross-linking agent, and the gel has excellent biocompatibility and antifouling properties; (3) the prepared hydrogel has excellent mechanical properties due to the presence of hydrogen bonds and electrostatic interactions. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 It is the nuclear magnetic spectrum of the intermediate (Urea) containing tertiary amino group and urea group prepared by the present invention.

[0027] Figure 2 The figure is the nuclear magnetic spectrum of the urea-sulfobetaine acrylic acid monomer (Urea-SBAA) prepared by the present invention.

[0028] Figure 3 The figure is the nuclear magnetic spectrum of urea methacrylate sulfobetaine monomer (Urea-SBMA) prepared by the present invention.

[0029] Figure 4 This is a photo of the urea methacrylate sulfobetaine (Urea-SBMA) zwitterionic hydrogel prepared by the present invention.

[0030] Figure 5 The stress-strain curve of the urea methacrylate sulfobetaine (Urea-SBMA) zwitterionic hydrogel prepared by the present invention in water. DETAILED DESCRIPTION

[0031] The technical solution of the present invention is further described below in conjunction with specific embodiments, but the scope of the present invention is not limited thereto.

[0032] The nuclear magnetic resonance spectrometer (AVANCE AV 400MHz) was used to perform nuclear magnetic H spectrum test ( 1 H NMR) was used as solvent, and the test was carried out at room temperature. The analysis was performed using MestReNova software. The H NMR spectrum proved that all monomers were successfully synthesized. The mechanical properties of the prepared multi-hydrogen bonded zwitterionic hydrogel were tested using a universal press tester (CTM6002).

[0033] Example 1

[0034] (1) The synthesis method of urea acrylate sulfobetaine monomer (Urea-SBAA) is as follows:

[0035] Step 1: Weigh the monomer N,N-dimethylethylenediamine (1.0g), 2-isocyanoethyl acrylate (1.6g), and hydroquinone inhibitor (2.5mg) in a molar ratio of 1:1. Dissolve 2-isocyanoethyl acrylate (1.6g) in 4ml of anhydrous tetrahydrofuran, and then add the weighed hydroquinone; dissolve N,N-dimethylethylenediamine in 25ml of anhydrous tetrahydrofuran, and then slowly drop the anhydrous tetrahydrofuran solution of 2-isocyanoethyl acrylate into the N,N-dimethylethylenediamine solution under an ice-water bath, stirring while dropping, remove the ice-water bath after the dropwise addition, react for 12 hours, and remove the solvent from the solution after the reaction by rotary evaporation on a low-temperature rotary evaporator to obtain an intermediate containing a tertiary amino group and a urea group (double bond without methyl (Urea)), the structure of which is shown below:

[0036]

[0037] 1 H NMR spectrum is attached Figure 1 As shown, 1 H NMR (D2O): δ=6.38; 5.95 (H1, CH2=CH); 6.17 (H2, CH2=CH-); 4.21 (H3, -COO-CH2-); 3.31 (H4, -CH2-NH-); 3.40 (H7, -NH-CH2-); 3.40 (H8, -NH-CH2-CH2-); 2.48 (H 9、10 , -N-(CH3)2) ppm. This proves that the vinyl intermediate containing tertiary amine and urea (double bond without methyl group (Urea)) was successfully synthesized.

[0038] Step 2: Weigh 5 mmol (1.146 g) of the Urea intermediate obtained in the first step, 5 mmol (0.611 g) of 1,3-propane sultone, and 1.1 mg of hydroquinone in a molar ratio of 1:1. Dissolve the Urea monomer in 25 ml of anhydrous tetrahydrofuran, and then add the weighed hydroquinone; then dissolve 1,3-propane sultone in 5 ml of anhydrous tetrahydrofuran, and slowly drop the 1,3-propane sultone solution into the anhydrous tetrahydrofuran solution of Urea at room temperature, stirring while dropping, and react at 45°C for 12 hours after the addition is complete. The solution after the reaction is precipitated with anhydrous ether, and then dried in a vacuum drying oven to obtain urea-sulfobetaine acrylate monomer (Urea-SBAA), the structural formula of which is shown below:

[0039]

[0040] 1 H NMR spectrum is attached Figure 2 As shown, 1H NMR (D2O): δ=6.40; 5.97 (H1, CH2=CH-); 6.19 (H2, CH2=CH-); 4.24 (H3, -COO-CH2 -); 3.44 (H4, -CH2-NH-); 3.61 (H7, -NH-CH2-); 3.50 (H8, -NH-CH2-CH2-); 3.15 (H 9、10 , -N-(CH3)2-CH2-); 3.44(H 11 , -N-(CH3)2-CH2-); 2.23(H 12 , -CH2-CH2-SO3); 2.96(H 13 , -CH2-CH2-SO3) ppm. This proves that the urea-acrylic acid-containing sulfobetaine monomer (Urea-SBAA) was successfully synthesized.

[0041] (2) The preparation method of urea sulfobetaine acrylate (Urea-SBAA) hydrogel is as follows:

[0042] The prepared zwitterionic sulfobetaine monomer Urea-SBAA was weighed and dissolved in deionized water to prepare a solution with a molar concentration of 4 mol / L. 0.1% 2959 photoinitiator was added, and the solution was cured under ultraviolet light for 60 minutes, then demolded and soaked in deionized water for 3 days to reach swelling equilibrium, and finally the Urea-SBAA hydrogel was obtained.

[0043] Example 2

[0044] (1) The synthesis method of urea methacrylate sulfobetaine monomer (Urea-SBMA) is as follows:

[0045] Step 1: Weigh 10 mmol (1.552 g) of 2-isocyanoethyl methacrylate monomer, 20 mmol (1.764 g) of N, N-dimethylethylenediamine monomer, and hydroquinone inhibitor (2.2 mg) in a molar ratio of 1:2, dissolve N, N-dimethylethylenediamine in 25 ml of anhydrous tetrahydrofuran, then dissolve 2-isocyanoethyl methacrylate in 4 ml of anhydrous tetrahydrofuran and add hydroquinone, slowly dropwise add the anhydrous tetrahydrofuran solution of 2-isocyanoethyl acrylate to the N, N-dimethylethylenediamine solution under an ice-water bath, stirring while dropping, remove the ice-water bath after the dropwise addition, react overnight (12 hours) under nitrogen protection, and remove the solvent from the solution after the reaction by rotary evaporation on a low-temperature rotary evaporator to obtain an intermediate (double bond with methyl (Urea-MA)) containing a tertiary amino group and a urea group, the structure of which is shown below:

[0046]

[0047] Step 2: Weigh 10 mmol (2.433 g) of Urea-MA intermediate, 20 mmol (1.343 g) of 1,3-propane sultone and hydroquinone (2.2 mg) in a molar ratio of 1:1.1. Dissolve Urea-MA in 25 ml of anhydrous tetrahydrofuran, then add the weighed hydroquinone; then dissolve 1,3-propane sultone in 5 ml of anhydrous tetrahydrofuran, slowly drop the 1,3-propane sultone solution into the anhydrous tetrahydrofuran solution of Urea-MA at room temperature, stirring while dropping, react at 50°C for 12 hours after the addition is complete, precipitate the solution with anhydrous ether, and then dry it in a vacuum oven to obtain methacrylate urea sulfobetaine monomer (Urea-SBMA), the structural formula of which is shown below:

[0048]

[0049] 1 H NMR spectrum is attached Figure 3 As shown, 1 H NMR (D2O): δ=6.11; 5.71 (H1, CH2= (CH)3-); 1.90 (H1, CH2= (CH)3-); 4.22 (H3, -COO- CH2-); 3.44(H4,-CH2-NH-); 3.60(H7,-NH-CH2-); 3.49(H8,-NH-CH2-CH2-); 3.14(H 9、10 , -N-(CH3)2-CH2-); 3.44(H 11 , -N-(CH3)2-CH2-); 2.22(H 12 , -CH2-CH2-SO3); 2.95(H 13 , -CH2-CH2-SO3) ppm. This proves that urea methacrylate sulfobetaine monomer (Urea-SBMA) was successfully synthesized.

[0050] (2) The preparation method of urea methacrylate sulfobetaine (Urea-SBMA) hydrogel is as follows:

[0051] The prepared zwitterionic sulfobetaine monomer Urea-SBMA was weighed and dissolved in deionized water to prepare a solution with a molar concentration of 5 mol / L. 0.1% 1173 photoinitiator was added, and the solution was cured under ultraviolet light for 180 minutes, then demolded and soaked in deionized water for 3 days to reach swelling equilibrium, and finally the Urea-SBMA hydrogel was obtained.

[0052] Urea-SBMA hydrogel pictures Figure 4As shown, it can be seen that Urea-SBMA can form gel even without adding a cross-linking agent, and the gel is a transparent elastic solid. The compression resistance of the hydrogel was further tested at room temperature using a universal testing machine (CTM6002) with a 500N load cell. Before the experiment, all tested hydrogels were balanced in water and then cut into cylinders (5 mm in diameter and 2 mm in thickness) using a biopsy punch. The crosshead speed was set to 1 mm / min. Figure 5 As shown, it can be seen that even without adding a cross-linking agent, the compressive fracture stress of the hydrogel can reach 1.22 MPa, which is due to the hydrogen bonds and electrostatic interactions in the hydrogel.

[0053] Example 3

[0054] (1) The synthesis method of urea methacrylate sulfobetaine monomer (Urea-SBMA) is as follows:

[0055] Step 1: Weigh 5 mmol (0.441 g) of monomer N,N-dimethylethylenediamine, 10 mmol (1.552 g) of 2-isocyanoethyl methacrylate, and 0.2% hydroquinone inhibitor (2.2 mg) at a molar ratio of 0.5:1, dissolve N,N-dimethylethylenediamine in 25 ml of anhydrous tetrahydrofuran, then dissolve 2-isocyanoethyl methacrylate in 4 ml of anhydrous tetrahydrofuran and add hydroquinone, slowly drop the anhydrous tetrahydrofuran solution of 2-isocyanoethyl acrylate into the N,N-dimethylethylenediamine solution under an ice-water bath, stirring while dropping, remove the ice-water bath after the dropwise addition, react overnight (12 hours) under nitrogen protection, and remove the solvent from the solution after the reaction by rotary evaporation on a low-temperature rotary evaporator to obtain an intermediate (double bond with methyl (Urea-MA)) containing a tertiary amino group and a urea group, the structure of which is shown below:

[0056]

[0057] Step 2: Weigh 10 mmol (2.433 g) of Urea-MA intermediate, 20 mmol (2.433 g) of 1,3-propane sultone and 2‰ mol (2.2 mg) of hydroquinone in a molar ratio of 1:2. Dissolve Urea-MA in 25 ml of anhydrous tetrahydrofuran, then add the weighed hydroquinone; then dissolve 1,3-propane sultone in 4 ml of anhydrous tetrahydrofuran, slowly drop the 1,3-propane sultone solution into the anhydrous tetrahydrofuran solution of Urea-MA at room temperature, stirring while dropping, react at 60°C for 12 hours under nitrogen protection after the addition, precipitate the solution with anhydrous ether, and then dry it in a vacuum oven to obtain methacrylate urea sulfobetaine monomer (Urea-SBMA), the structural formula of which is shown below:

[0058]

[0059] 1 H NMR spectrum is attached Figure 3 As shown, 1 H NMR (D2O): δ=6.11; 5.71 (H1, CH2= (CH)3-); 1.90 (H1, CH2= (CH)3-); 4.22 (H3, -COO- CH2-); 3.44(H4,-CH2-NH-); 3.60(H7,-NH-CH2-); 3.49(H8,-NH-CH2-CH2-); 3.14(H 9、10 , -N-(CH3)2-CH2-); 3.44(H 11 , -N-(CH3)2-CH2-); 2.22(H 12 , -CH2-CH2-SO3); 2.95(H 13 , -CH2-CH2-SO3) ppm. This proves that urea methacrylate sulfobetaine monomer (Urea-SBMA) was successfully synthesized.

[0060] (2) The preparation method of urea methacrylate sulfobetaine (Urea-SBMA) hydrogel is as follows:

[0061] The prepared zwitterionic sulfobetaine monomer Urea-SBMA was weighed and dissolved in deionized water to prepare a solution with a molar concentration of 3 mol / L. 0.1% mol of ammonium persulfate was added as a thermal initiator, and the mixture was cured at 60°C for 12 hours, then demolded and immersed in deionized water for 3 days to achieve swelling equilibrium, and finally the Urea-SBMA hydrogel was obtained.

[0062] According to the content of the present invention, the process parameters can be adjusted to achieve the preparation of hydrogels, and the performance shown by the test is basically consistent with that of the present invention. The above is an exemplary description of the present invention. Without departing from the core of the present invention, any simple deformation, modification or equivalent replacement that can be made by other technicians in this field without spending creative labor falls within the protection scope of the present invention.

Claims

1. A urea sulfobetaine zwitterionic hydrogel, characterized in that: The urea sulfobetaine zwitterion monomer is dissolved in water or phosphate buffer solution to prepare a solution with a molar concentration of 1 to 6 mol / L, and then a photoinitiator or a thermal initiator is added at a molar ratio of 0.1 to 2% relative to the monomer, and then injected into a closed mold, and the monomer polymerization is initiated by photoinitiation or thermal initiation. After a period of time, the mold is removed and the unreacted monomer is soaked in water for at least 1 day to remove the unreacted monomer, so as to obtain the urea sulfobetaine zwitterion hydrogel; the hydrogel can be gelled without the addition of an additional crosslinking agent through hydrogen bonding and electrostatic interaction of the sulfonic acid group part, and the hydrogel has excellent mechanical properties and antifouling properties; the polymer molecular structure is shown as follows: Wherein, R is CH3 or H; m is the degree of polymerization of the zwitterionic monomer, which is 20 to 5000; and n is 1.

2. The urea sulfobetaine zwitterionic hydrogel according to claim 1, characterized in that: The initiator is 2-hydroxy-2-methyl-1-phenyl-1-propanone (photoinitiator 1173) or 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone (photoinitiator 2959) or ammonium persulfate.

3. The urea sulfobetaine zwitterionic hydrogel according to claim 1, characterized in that: When 2-hydroxy-2-methyl-1-phenyl-1-propanone (photoinitiator 1173) or 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone (photoinitiator 2959) is selected as the initiator for cross-linking, the monomer polymerization is initiated in an ultraviolet light cross-linking instrument, and the reaction time is 10 to 180 minutes; when ammonium persulfate is selected as the thermal initiator, the monomer polymerization is initiated by heating in an oven, the polymerization reaction temperature is 60-80° C., and the polymerization time is 12 hours.

4. The urea sulfobetaine zwitterionic hydrogel according to claim 1, characterized in that: The synthesis method of urea sulfobetaine zwitterion monomer is as follows: Step 1: reacting (methyl) acrylic acid isocyanate and an ammonia monomer containing a tertiary amino group to generate a urea group to obtain a vinyl intermediate containing a urea group and a tertiary amino group; weighing (methyl) acrylic acid isocyanoethyl and an ammonia monomer containing a tertiary amino group in a molar ratio of 1: (0.5-2) respectively and dissolving them in anhydrous tetrahydrofuran or anhydrous acetone, adding the (methyl) acrylic acid isocyanoethyl solution dropwise to the ammonia monomer solution containing a tertiary amino group under stirring at 0-10° C., and reacting at 0-10° C. for 12 hours under nitrogen protection; the solution after the reaction is subjected to rotary evaporation by a low-temperature rotary evaporator to remove the solvent to obtain a vinyl intermediate containing a tertiary amino group and a urea group; the structure of the vinyl intermediate is as follows: Wherein, R is CH3 or H; n is 1; The structure of isocyanoethyl (meth)acrylate is shown below: Wherein, R is CH3 or H; The structure of the above-mentioned amino monomer containing tertiary amine group is shown below: Where n is 1; Step 2: The vinyl intermediate containing urea and tertiary amino groups obtained in step 1 is subjected to a ring-opening reaction with 1,3-propane sultone to obtain a urea-based sulfobetaine zwitterionic monomer; the intermediate obtained in step 1 is weighed and dissolved in 25 ml of anhydrous tetrahydrofuran or anhydrous acetone in a molar ratio of 1:(1-2); then 1-2 equivalents of 1,3-propane sultone are weighed and added dropwise to the intermediate solution while stirring; after the addition is complete, the dropping funnel is rinsed with 200 microliters of anhydrous tetrahydrofuran or anhydrous acetone, the reaction is stirred at 45-60° C. for 12 hours, ether is used for precipitation and centrifugation to obtain a white precipitate, which is dried in a vacuum drying oven to obtain a urea-based sulfobetaine zwitterionic monomer; its structure is shown in the figure below: Wherein, R is CH3 or H; n is 1.

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