A zwitterionic compound, a preparation method thereof and a preparation method of a contact lens with an anti-fouling function

Abstract

The application discloses a kind of zwitterionic compounds and its preparation method and the preparation method of the contact lens with antifouling function. First, diisocyanate compound is reacted with hydroxyl-containing acrylate compound to obtain urethane-containing acrylate isocyanate half-enclosure, then it is reacted with active hydrogen-containing tertiary amine to obtain urea group, urethane group-containing acrylate monomer, and then zwitterionic is realized by β-propiolactone ring opening. The application also combines the obtained zwitterionic compound monomer to the contact lens by free radical initiation polymerization, improves the hydrophilicity of the lens, and obtains the contact lens with excellent antifouling function. The structure of this hydrogen bond, zwitterionic crosslinking network avoids the vicious development of contact lens biofouling adhesion, and is a promising strategy to solve the problem of contact lens biofouling adhesion.

Description

Technical Field

[0001] This invention belongs to the field of polymer science and technology, specifically relating to an amphoteric compound and its preparation method, as well as a method for preparing orthokeratology lenses with anti-fouling function. Background Technology

[0002] Myopia is a major global public health problem. The cause of myopia is the continuous elongation of the eye's axial length, causing light to focus in front of the retina instead of onto it, thus affecting normal vision. Orthokeratology (Ortho-k) lenses are considered an excellent means of myopia control. They apply mechanical pressure to the cornea through a flat base curve in the central region and negative pressure suction through a steeper reversal curve in the mid-periphery, reshaping the cornea appropriately. By changing the refractive power of the peripheral cornea, peripheral myopic defocus is created, thereby preventing undesirable axial elongation and slowing the progression of myopia.

[0003] Orthokeratology (Ortho-k) lenses contain fluorine and silicone-based acrylates, making their surface hydrophobic. Prolonged wear of Ortho-k lenses can cause discomfort on the ocular surface. Furthermore, the hydrophobic components can cause proteins and non-polar lipids such as cholesterol from tears to deposit on the surface, forming biofouling that can harm the patient's vision. In addition, microorganisms on the ocular surface, such as Escherichia coli, Staphylococcus aureus, and Candida albicans, can adhere to the surface of the Ortho-k lens, causing bacterial infections, inflammation, and damage to corneal epithelial cells, seriously endangering the patient's physical and mental health.

[0004] Carboxybetaine is widely used in biomedical materials. Traditional carboxybetaine has a relatively simple side chain, containing only acrylate or acrylamide and zwitterionic groups. Furthermore, the synthesis of carboxybetaine currently mainly involves the reaction of tertiary amines with α-halo acids or sodium α-haloates. When using α-halo acids as raw materials, they are generally used in excess, but this results in an irritating product. When using sodium α-haloates as raw materials, ion exchange, simple distillation, and extractive crystallization are commonly used to remove sodium chloride generated during the reaction. These processes are cumbersome and difficult to completely remove, making it hard to obtain a product with high purity. Summary of the Invention

[0005] The purpose of this invention is to provide an amphoteric compound and its preparation method, as well as a method for preparing orthokeratology lenses with anti-fouling function. Firstly, a novel amphoteric compound monomer (novel amphoteric carboxybetaine) containing hydrogen bond donors and acceptors (carbamate, urea group) with intermolecular non-covalent interactions is provided, along with its preparation method, and then applied to orthokeratology lenses. For anti-fouling, amphoteric carboxybetaine is selected and modified onto the orthokeratology lens. Due to its strong electrostatic hydration, the amphoteric ions can form a dense hydration layer on the surface and inside of the material, effectively preventing the adsorption and adhesion of proteins, lipids, bacteria, and cells, thus achieving anti-fouling and damage prevention.

[0006] To achieve the above objectives, the present invention adopts the following technical solution: An amphoteric compound has the following structural formula:

[0007] The side chains of the zwitterionic compounds of the present invention contain urethane groups, urea groups, and carboxy-betaine groups.

[0008] The preparation method of the above-mentioned zwitterionic compound includes the following steps: 1) In the presence of a catalyst and a polymerization inhibitor, hydroxyl-containing acrylate compounds and diisocyanate compounds are reacted in an inert atmosphere to obtain isocyanate semi-encapsulated compounds containing urethane acrylates.

[0009] Preferably, the hydroxyl-containing acrylate compound is one or more of 2-hydroxyethyl acrylate (HEA), 4-hydroxybutyl acrylate, and 2-hydroxyethyl methacrylate.

[0010] Preferably, the diisocyanate compound is one or more of hexamethylene diisocyanate (1,6-hexamethylene diisocyanate, HDI), pentamethylene diisocyanate, and isophorone diisocyanate.

[0011] Preferably, the catalyst is selected from one or more of dibutyltin dilaurate (DBTDL), stannous octoate, and triethylamine, with dibutyltin dilaurate (DBTDL) being the most preferred. The molar ratio of the reactants (the sum of hydroxyl-containing acrylate compounds and diisocyanate compounds) to the catalyst is 1:0.01-1:0.05, with 1:0.017 being the most preferred.

[0012] Preferably, the reaction temperature is 40-80℃, more preferably 40-60℃, and even more preferably 60℃; the reaction time is 1-8h, more preferably 1-2h, and even more preferably 1h.

[0013] Preferably, the polymerization inhibitor is one or more of hydroquinone, p-methoxyphenol (4-methoxyphenol), and 2,6-di-tert-butyl-p-cresol, with p-methoxyphenol being the most preferred; the molar ratio of the reactant (hydroxyl-containing acrylate compound) to the polymerization inhibitor is 1:0.01-1:0.05, with 1:0.014 being the most preferred.

[0014] Preferably, the molar ratio of the hydroxyl-containing acrylate compound to the diisocyanate compound in the reactants is 1:1-1.3:1, more preferably 1.2:1-1:1, and even more preferably 1:1.

[0015] Preferably, the reaction solvent is an anhydrous solvent, which is one or more of anhydrous acetonitrile, anhydrous toluene, anhydrous chloroform, and anhydrous N,N-dimethylformamide, with anhydrous acetonitrile being the most preferred; the molar ratio of the reactants (the sum of hydroxyl-containing acrylate compounds and diisocyanate compounds) to the solvent is 1:4 to 1:8, with 1:4.2 being the most preferred.

[0016] Preferably, the inert atmosphere is one or both of nitrogen and helium.

[0017] Preferably, the reaction is conducted in the dark.

[0018] Specifically, in the dark and under an inert atmosphere (e.g., nitrogen), a diisocyanate compound (e.g., 1,6-hexamethylene diisocyanate (HDI)), a reaction solvent (e.g., anhydrous acetonitrile), a polymerization inhibitor (e.g., p-methoxyphenol), and a catalyst (e.g., dibutyltin dilaurate (DBTDL)) are placed in a round-bottom flask and stirred for 10-15 minutes to obtain a reaction solution. The temperature of the reaction solution is raised to 40-45°C, and a hydroxyl-containing acrylate compound (e.g., 2-hydroxyethyl acrylate (HEA)) is dissolved in the reaction solvent (e.g., anhydrous acetonitrile) to obtain a hydroxyl-containing acrylate compound solution. This hydroxyl-containing acrylate compound solution is slowly (0.3-0.5 drops / second) added dropwise to the above reaction solution. Then, the temperature is slowly raised to 40-80°C (heating rate 0.5-1.5°C / min), and after reacting for 1-2 hours, a clear and transparent solution is obtained, which is the isocyanate semi-encapsulated body containing acrylate groups. The volume ratio of the first added reaction solvent (e.g., anhydrous acetonitrile) to the second added reaction solvent (e.g., anhydrous acetonitrile) is 1:1-3:1, preferably 2:1.

[0019] 2) Under low temperature and inert atmosphere, the isocyanate semi-encapsulated compound containing urethane ester obtained in step 1) is subjected to nucleophilic addition reaction with a tertiary amine compound containing active hydrogen to obtain an acrylate monomer containing urea group and urethane group (denoted as AMA).

[0020] Preferably, the tertiary amine compound containing active hydrogen is one or more of N,N-dimethylethylenediamine, N,N-dimethyl-1,3-propanediamine, and 4-(dimethylamino)butamine.

[0021] Preferably, the molar ratio of the diisocyanate compound to the tertiary amine compound containing active hydrogen in step 1) is 0.7:1-1:1, more preferably 0.8:1-1:1, and even more preferably 1:1.

[0022] Preferably, the reaction temperature is 0-10℃, more preferably 0-4℃; the reaction time is 0.5-3h, more preferably 0.5-1h, and even more preferably 45min.

[0023] Preferably, the reaction solvent is an anhydrous solvent, which is one or more of anhydrous dichloromethane, anhydrous chloroform, anhydrous toluene, anhydrous acetonitrile, and anhydrous N,N-dimethylformamide, with anhydrous acetonitrile being the most preferred; the molar ratio of the reactants (the semi-encapsulated isocyanate containing acrylate and the total N,N-dimethylethylenediamine) to the solvent is 1:20-1:30, with 1:22 being the most preferred.

[0024] Preferably, the inert atmosphere is one or both of nitrogen and helium.

[0025] Preferably, the reaction is conducted in the dark.

[0026] Specifically, in the dark, under an inert atmosphere (e.g., nitrogen), at 0-10°C, a reaction solvent (e.g., anhydrous acetonitrile) containing an active hydrogen tertiary amine compound (e.g., N,N-dimethylethylenediamine) is added dropwise to the clear, transparent solution obtained in step 1) at a rate of 0.2 drops / second to 0.5 drops / second, and the addition is completed in approximately 15-30 minutes. More reaction solvent (e.g., anhydrous acetonitrile) is added midway through the process, and the reaction is stirred for 0.5-1 hour. The solution is then filtered, washed with the reaction solvent (e.g., anhydrous acetonitrile), and dried under vacuum to obtain a white solid (AMA). In this process, the volume ratio of the tertiary amine compound containing active hydrogen (e.g., N,N-dimethylethylenediamine) to the reaction solvent (e.g., anhydrous acetonitrile) in the reaction solvent solution (e.g., anhydrous acetonitrile) is 1:10 to 1:15, and the volume ratio of the reaction solvent (e.g., anhydrous acetonitrile) to the reaction solvent (e.g., anhydrous acetonitrile) added midway is 1:1 to 1:1.5, preferably 2:3.

[0027] 3) Under an inert atmosphere, the acrylate monomer containing urea and carbamate groups obtained in step 2) reacts with β-propiolactone to achieve zwitterionization, resulting in a zwitterion compound containing urea and carbamate groups as hydrogen bond donors and acceptors (i.e., acrylate carboxybetaine compounds containing urea and carbamate groups, denoted as ACBMA).

[0028] Preferably, the reaction temperature is 0-25℃ and the reaction time is 17-40h.

[0029] Preferably, a low-temperature reaction is carried out first, followed by a room-temperature reaction; the low-temperature reaction temperature is 0-10℃, preferably 4℃; the low-temperature reaction time is 1-4h, preferably 1-2h; and the room-temperature reaction time is 16-36h, preferably 16-24h.

[0030] Preferably, the reaction solvent is one or more of anhydrous chloroform, anhydrous dichloromethane, and anhydrous dimethyl sulfoxide, with anhydrous dichloromethane being the most preferred; the molar ratio of the reactants (the sum of acrylate monomers containing urea groups and urethane groups and β-propiolactone) to the solvent is 1:8 to 1:16, with 1:8.2 being the most preferred.

[0031] Preferably, the molar ratio of acrylate monomers containing urea groups and urethane groups to β-propiolactone is 1:1 to 1:1.5, more preferably 1:1 to 1:1.02, and even more preferably 1:1.

[0032] Preferably, the inert atmosphere is one or both of nitrogen and helium.

[0033] Preferably, the reaction is conducted in the dark.

[0034] Specifically, in the dark and under an inert atmosphere (e.g., nitrogen atmosphere), the white solid obtained in step 2) (an acrylate monomer containing urea and carbamate groups) is dissolved in a reaction solvent (e.g., anhydrous dichloromethane) to obtain an acrylate monomer solution containing urea and carbamate groups. β-propiolactone is dissolved in the reaction solvent (e.g., anhydrous dichloromethane) to obtain a β-propiolactone solution. The β-propiolactone solution is slowly added dropwise (0.5 drops / second to 1 drop / second) to the above acrylate monomer solution containing urea and carbamate groups at 0-10°C. The reaction is carried out at 0-10°C for 2-4 hours, followed by stirring at room temperature for 22-24 hours. After centrifugation, a colorless oily substance is obtained, which is washed with a solvent (e.g., anhydrous dichloromethane), washed with water, centrifuged, and freeze-dried to obtain a colorless oily viscous solid (ACBMA).

[0035] The above-mentioned zwitterionic compounds are used in the preparation of orthokeratology lenses with antifouling function.

[0036] A method for preparing an orthokeratology lens with anti-fouling function includes the following steps: (1) Four monomers (methacryloyloxypropyltris(trimethylsiloxane)silane (TRIS) monomer, 1-vinyl-2-pyrrolidone (NVP) monomer, N,N-dimethylacrylamide (DMA) monomer, 1,1,1,3,3,3-hexafluoroisopropylisobutylene ester (HFMA) monomer), initiator and crosslinking agent are mixed and mixed evenly. The mixture is then added to a mold and polymerized under ultraviolet light to obtain the corneal reshaping lens substrate (denoted as HG).

[0037] Preferably, the initiator is a photoinitiator, specifically one or both of 2-hydroxy-2-methylphenylacetone (D-1173) and 1-hydroxycyclohexylphenyl ketone.

[0038] Preferably, the crosslinking agent is one or both of triethylene glycol trimethacrylate (TGDMA) and ethylene glycol dimethacrylate (EGDMA).

[0039] Preferably, in the total amount of the four monomers—methacryloyloxypropyltris(trimethylsiloxane)silane (TRIS), 1-vinyl-2-pyrrolidone (NVP), N,N-dimethylacrylamide (DMA), and 1,1,1,3,3,3-hexafluoroisopropylisobutylene ester (HFMA)—TRIS, NVP, DMA, and HFMA monomers account for 30-35 wt.%, 20-25 wt.%, 10-15 wt.%, and 25-30 wt.%, respectively. More preferably, the proportions of TRIS, NVP, DMA, and HFMA monomers are 35 wt.%, 20 wt.%, 15 wt.%, and 30 wt.%, respectively.

[0040] Preferably, the initiator accounts for 0.5-1% wt.% of the total amount of the four monomers TIS, TIS, DMA, and HFMA, and more preferably 0.5 wt.%.

[0041] Preferably, the crosslinking agent accounts for 0.5-2 wt.% of the total amount of the four monomers TIS, TIS, DMA, and HFMA, and more preferably 1 wt.%.

[0042] Preferably, when the crosslinking agent is triethylene glycol trimethacrylate (TGDMA) or ethylene glycol dimethacrylate (EGDMA), the mass ratio of triethylene glycol trimethacrylate (TGDMA) to triethylene glycol trimethacrylate (TGDMA) is 0.5:1 to 1.5:1, preferably 1:1.

[0043] Preferably, after mixing thoroughly, the mixture is sonicated for 1-5 minutes to remove any air bubbles that may be present in the liquid.

[0044] Preferably, the wavelength of the ultraviolet light is 305-325nm, more preferably 305nm; the polymerization time is 1-2h, more preferably 1h.

[0045] Preferably, after polymerization, the unreacted monomers, crosslinking agents, and initiators are washed with an ethanol aqueous solution (25%-50% ethanol) for 12-36 hours, preferably 24 hours, followed by washing with ultrapure water for 12-36 hours, preferably 24 hours.

[0046] Preferably, the product is dried after washing, and the drying conditions are: vacuum drying at 35-40℃ for 24-48 hours.

[0047] Specifically, TRIS monomer, DMA monomer, NVP monomer, HFMA monomer, photoinitiator D-11173, and crosslinking agents DGDMA and TGDMA are mixed uniformly in a ratio of 35 wt.%, 20 wt.%, 15 wt.%, 30 wt.%, 0.5 wt.%, 0.5 wt.%, and 0.5 wt.%, and ultrasonicated for 1-5 minutes. The mixture is then photopolymerized under 305-325 nm ultraviolet light for 1-2 hours, demolded, and the polymerized lens is immersed in a 50% ethanol solution for 12-24 hours to remove unreacted monomers, crosslinking agents, and initiators. Subsequently, the freshly prepared lens is removed and immersed in ultrapure water for 12-24 hours to remove ethanol residue and restore lens performance. It is then vacuum dried at 40°C for 24 hours to obtain a dried orthokeratology lens, denoted as HG.

[0048] (2) Dissolve the above zwitterionic compound monomer (ACBMA) in water to obtain a monomer solution, and add an initiator and a crosslinking agent to it, mix them evenly to obtain a reaction solution; immerse the corneal reshaping lens in the reaction solution, and polymerize it under ultraviolet light to obtain a corneal reshaping lens with antifouling function (denoted as pACBMA-HG).

[0049] Preferably, the initiator is a photoinitiator, specifically one or both of 2-hydroxy-2-methylphenylacetone (D-1173) and 1-hydroxycyclohexylphenyl ketone.

[0050] Preferably, the crosslinking agent is one or both of triethylene glycol trimethacrylate (TGDMA) and ethylene glycol dimethacrylate (EGDMA).

[0051] Preferably, the mass ratio of zwitterionic monomer (ACBMA), initiator, and crosslinking agent is 0.02-0.1:0.01-0.02:0.01-0.04, and more preferably 0.08:0.01:0.02. For example, the mass of ACBMA monomer is 0.02g-0.1g, the mass of initiator is 0.01-0.02g, and the mass of crosslinking agent is 0.01-0.04g; more preferably, the mass of ACBMA is 0.08g, the mass of initiator is 0.01g, and the mass of crosslinking agent is 0.02g.

[0052] Preferably, when the crosslinking agent is triethylene glycol trimethacrylate (TGDMA) or ethylene glycol dimethacrylate (EGDMA), the mass ratio of triethylene glycol trimethacrylate (TGDMA) to triethylene glycol trimethacrylate (TGDMA) is 0.5:1 to 1.5:1, preferably 1:1.

[0053] Preferably, the ratio of zwitterionic monomer (ACBMA) to water in the monomer solution is 0.02g-0.1g:5mL, and more preferably 0.08g:5mL.

[0054] Preferably, the method of uniform mixing is ultrasonic vibration, and the ultrasonic vibration time is 5-15 minutes.

[0055] Preferably, the soaking time is 12-36 hours (preferably 24 hours) to allow the crosslinking agent, initiator, and monomer to fully penetrate into the orthokeratology lens.

[0056] Preferably, the wavelength of the ultraviolet light is 305-325nm, more preferably 305nm; the photopolymerization time is 3-5h, more preferably 3h.

[0057] Preferably, after polymerization, the product is washed with water for 24-48 hours to remove unreacted crosslinking agents, initiators, and monomers. The water is changed every 6-12 hours during the washing process.

[0058] Preferably, the product is dried after washing, and the drying conditions are: vacuum drying at 35-40℃ for 24-48 hours.

[0059] Specifically, ACBMA is dissolved in water, and a photoinitiator and crosslinking agent are added. The mixture is ultrasonically vibrated for 5-15 minutes, then placed in a substrate HG and allowed to soak for 12-36 hours (allowing the crosslinking agent, initiator, and monomer to fully penetrate the orthokeratology lens). The lens is then irradiated under 305-325 nm ultraviolet light for 3-5 hours, washed with water for 24-48 hours to remove unreacted crosslinking agent, initiator, and monomer, and then vacuum-dried at 35-40℃ for 24-48 hours to obtain an orthokeratology lens with anti-fouling and self-healing functions, denoted as pACBMA-X-HG. Here, X represents the initial concentration of the ACBMA monomer.

[0060] The above-described preparation method yields orthokeratology lenses with anti-fouling function.

[0061] Protein adsorption was evaluated on orthokeratology lenses (pACBMA-HG) with antifouling function. Specifically, for protein adsorption, pACBMA-X-HG was placed in a 1-10 mg / mL solution of lysozyme or denatured lysozyme protein and incubated at 33-34℃ for 8-12 h. Quantitative detection of proteins was performed using MircoBCA.

[0062] Bacterial adhesion was evaluated on orthokeratology lenses (pACBMA-HG) with antifouling function. *Escherichia coli* and *Staphylococcus aureus* were used. Specifically, for bacterial adhesion, pACBMA-X-HG was placed in *Escherichia coli* or *Staphylococcus aureus* bacterial suspension and incubated at 37°C for 8-12 hours. Bacterial adhesion on the sample surface was observed using a laser confocal microscope.

[0063] The beneficial effects of this invention are: This invention reacts diisocyanate compounds with hydroxyl-containing acrylate compounds to obtain isocyanate semi-encapsulated compounds containing urethane acrylates. These are then reacted with tertiary amines containing active hydrogen to obtain acrylate monomers containing urea and urethane groups. Amphoteric ionization is achieved through β-propiolactone ring-opening to prepare a zwitterionic compound with hydrogen bond donor and acceptor structures. This invention also incorporates the prepared zwitterionic compound monomers into orthokeratology lenses via free radical-initiated polymerization, improving the lens's hydrophilicity and resulting in orthokeratology lenses with excellent anti-fouling properties. The orthokeratology lenses prepared by this invention exhibit reduced lysozyme protein and denatured lysozyme adsorption amounts to 11.29±2.03% and 16.31±2.15%, respectively, with almost no adhesion of Escherichia coli and Staphylococcus aureus. This structure, with hydrogen bonds and a zwitterionic cross-linked network, avoids the malignant development of biofouling adhesion in orthokeratology lenses, representing a promising strategy for solving the biofouling problem. Attached Figure Description

[0064] Figure 1The image shows the NMR mass spectrum of AMA, where A) is NMR and B) is hydrogen mass spectrum.

[0065] Figure 2 The image shows the NMR mass spectrum of ACBMA, where A) is NMR and B) is sodium-added mass spectrum.

[0066] Figure 3 Infrared spectra of homemade lenses and commercial lenses.

[0067] Figure 4 The images show the water contact angle and infrared spectrum of pACBMA-X-HG and HG, where A) is the water contact angle image and B) is the infrared spectrum.

[0068] Figure 5 The images show the adsorption diagrams of lysozyme protein and denatured lysozyme protein for pACBMA-X-HG and HG, where A) is the lysozyme protein adsorption diagram and B) is the denatured lysozyme protein diagram.

[0069] Figure 6 Adhesion diagram of pACBMA-16-HG and HG Escherichia coli and Staphylococcus aureus. Detailed Implementation

[0070] This invention provides an amphoteric compound and its preparation method, as well as a method for preparing an anti-fouling orthokeratology lens.

[0071] The zwitterionic compound has the following structural formula:

[0072] The preparation method of the above-mentioned zwitterionic compound includes the following steps: First, hydroxyl-containing acrylate compounds are reacted with diisocyanate compounds to obtain isocyanate semi-encapsulated compounds containing urethane acrylates; then, they are reacted with tertiary amines containing active hydrogen to obtain acrylate monomers containing urea groups and urethane structures, and then amphotericized with β-propiolactone to obtain a zwitterionic compound (denoted as ACBMA).

[0073] A method for preparing an orthokeratology lens with anti-fouling properties includes the following steps: The above-mentioned zwitterionic compound (ACBMA) was polymerized with ultraviolet light and then bonded to an orthokeratology lens (HG) to obtain an orthokeratology lens (pACBMA-HG) with anti-fouling function.

[0074] The following specific embodiments are for further explanation of the content of the present invention and should not be construed as limiting the present invention in any way.

[0075] Example 1 Protected from light, under a nitrogen atmosphere, 1,6-hexamethylene diisocyanate (2.1023 g, 12.5 mmol), anhydrous acetonitrile (10 mL), p-methoxyphenol (0.0125 g), and dibutyltin dilaurate (DBTDL, 5 mg) were placed in a round-bottom flask and stirred for 10 minutes. The reaction solution was heated to 40 °C, and 2-hydroxyethyl acrylate (1.4515 g, 12.5 mmol) was dissolved in 5 mL of anhydrous acetonitrile and slowly added dropwise (0.4 drops / second) to the above reaction solution. The temperature was then slowly increased to 60 °C (1 °C / min), and after 1 hour, a clear, transparent solution was obtained.

[0076] Example 2 In a light-protected, nitrogen-filled atmosphere under ice bath conditions (0-4°C), an anhydrous acetonitrile solution (20 mL) of N,N-dimethylethylenediamine (1.1019 g, 12.5 mmol) was added dropwise to the clear, transparent solution obtained in Example 1. The addition was completed over approximately 15 minutes, with an additional 30 mL of anhydrous acetonitrile added midway through the reaction. The mixture was stirred for 30 minutes. The solution was filtered, washed three times with anhydrous acetonitrile, and dried under vacuum at 35°C for 24 hours to obtain a white solid. The yield was 73%. The structure was determined by NMR spectroscopy. Figure 1 A, Mass spectrometry Figure 1 B is confirmed. NMR results show that the chemical shifts and peak areas of all hydrogen atoms on the alkyl groups correspond to those of the target compound, and the molecular weight of the hydrogenation peak in the mass spectrometry is 373.2453, indicating that compound AMA was successfully prepared.

[0077] Example 3 Protected from light, under a nitrogen atmosphere, 1.1167 g (3 mmol) of the white solid prepared in Example 1 was dissolved in 20 mL of anhydrous dichloromethane. 0.4324 g (6 mmol) of β-propiolactone was dissolved in 5 mL of anhydrous dichloromethane. Under ice bath conditions (0-4°C), the dichloromethane solution of β-propiolactone was slowly added dropwise (0.5 drops / second) to the above solution. The reaction was carried out in an ice bath for 2 h, followed by stirring at room temperature for 22 h. After centrifugation, a colorless oily substance was obtained, washed three times with anhydrous dichloromethane, washed with water, centrifuged, and freeze-dried to obtain a colorless, oily, viscous solid. The yield was 74.65%, and the structure was determined by NMR spectroscopy. Figure 2 A, Mass spectrometry Figure 2 B is confirmed. NMR results show that the chemical shifts and peak areas of all alkyl groups correspond to those of the target compound, and the molecular weight of the sodium-added peak in the mass spectrometry is 467.2476, indicating that compound ACBMA was successfully prepared.

[0078] Example 4 TRIS monomer, DMA monomer, NVP monomer, HFMA monomer, photoinitiator D-11173, crosslinking agent DGDMA, and crosslinking agent TGDMA were mixed in the following proportions: 35 wt.%, 20 wt.%, 15 wt.%, 30 wt.%, 0.5 wt.%, 0.5 wt.%, 0.5 wt.%, respectively. The mixture was then sonicated for 1 minute to remove any air bubbles. The mixture was then added to a lens film mold and polymerized under 305 nm UV light for 1 hour. After demolding, the polymerized lens was immersed in a 50% ethanol solution for 24 hours to remove unreacted monomers, crosslinking agents, and initiators. The freshly prepared lens was then removed and immersed in ultrapure water for 12 hours to remove residual ethanol and restore lens performance. It was then vacuum dried at 40°C for 24 hours to obtain a dried orthokeratology lens, denoted as HG. Infrared images of the self-made orthokeratology lens and a commercial orthokeratology lens (Alpha brand orthokeratology lens) are shown below. Figure 3 As shown. A CH peak (2961 cm⁻¹) of TRIS and C=O peaks (1771 cm⁻¹) of NVP and other monomers were detected, with peaks at 1040 cm⁻¹. -1 and 829 cm -1 A Si-O-Si peak of TRIS was detected at 1348 cm⁻¹. In addition, CF peaks of HFMA were detected at 1348 cm⁻¹ and 757 cm⁻¹. Comparison with the infrared spectrum of the commercial Alpha brand orthokeratology lens showed that the peak positions of the prepared orthokeratology lens were almost identical, proving the successful synthesis of a lens with a structure similar to that of commercial orthokeratology lenses.

[0079] Example 5 Preparation of Orthokeratology Lenses with Anti-fouling Function. The ACBMA monomer prepared in Example 3 was taken, and an appropriate amount of deionized water was added to prepare ACBMA monomer solutions of different concentrations (4, 8, 12, 16, and 20 mg / mL, respectively). 0.01 g of photoinitiator (D-1173) and 0.01 g of crosslinking agent (EGDMA, TGDMA) were added to 5 mL of the monomer solution, and the mixture was ultrasonically vibrated for 5 min to obtain a reaction solution. The orthokeratology lens prepared in Example 4 was immersed in the reaction solution for 24 h (allowing the monomer, initiator, and crosslinking agent to fully penetrate the pores of the orthokeratology lens). It was then irradiated under 305 nm ultraviolet light for 3 h to obtain a double-network orthokeratology lens. This lens was then immersed in water for 24 h (to remove unreacted monomer, crosslinking agent, and initiator), with the water changed every 6 hours. The lens was vacuum dried at 40 °C for 24 h to obtain a dried orthokeratology lens, denoted as pACBMA-X-HG (where X is the initial concentration of the ACBMA monomer, in mg / mL). As the concentration of ACBMA monomers continues to increase, the static water contact angle of orthokeratology lenses continues to decrease, and the infrared 1723cm... -1The stretching vibration peaks continuously increase, indicating that the combination of ACBMA and HG, water contact angle, infrared image as shown Figure 4 As shown in A and B.

[0080] Example 6 Evaluation of protein adsorption resistance of orthokeratology lenses. For protein adsorption, lysozyme protein (1.9 mg / mL, Beijing Innocare Technology Co., Ltd.) and denatured lysozyme protein (1.9 mg / mL) were selected. The denatured lysozyme protein was prepared as follows: a PBS solution of 1.9 mg / mL lysozyme protein at pH 7.4 was prepared and heated at 90°C for 5 minutes to obtain denatured lysozyme protein. The orthokeratology lens sample (pACBMA-X-HG) prepared in Example 5 was immersed in 2 mL of either lysozyme protein or denatured lysozyme protein PBS solution and incubated at 34°C and 90 rpm for 8 hours. HG was used as the control group. The sample was then washed three times with ultrapure water and immersed in SDS (sodium dodecyl sulfate, 1 wt%) solution for 2 hours at room temperature. 150 μL of the eluent was then added to 150 μL of Mirco BCA working solution (Thermo Scientific), in triplicate. The absorbance of the protein was measured at 562 nm using a microplate reader to evaluate the adsorption of lysozyme protein and denatured lysozyme protein. Figure 5 As shown in Figures A and B. The results showed that the adsorption capacity of lysozyme protein and denatured lysozyme of pACBMA-HG decreased to 11.29±2.03% and 16.31±2.15% respectively, indicating good antifouling effect.

[0081] Example 7 Evaluation of the antibacterial adhesion function of orthokeratology lenses. Staphylococcus aureus and Escherichia coli were used to evaluate bacterial adhesion. The orthokeratology lens sample (pACBMA-16-HG) prepared in Example 5 was immersed in 1 mL of bacterial solution (LB medium, cell density 1×10⁻⁶). 8 Incubate at 37°C for 12 hours (CFU / mL), with HG as the control group. Wash the bacterial suspension on the sample surface with sterile PBS buffer (pH 7.4), add bacterial viability staining solution (Beyotime) for staining, and observe under a laser confocal microscope. Figure 6 As shown in Figures A and B, the results indicate that pACBMA-HG showed almost no bacterial adhesion, demonstrating that adding zwitterionic monomers to the lens can effectively resist contamination.

Claims

1. A zwitterionic compound, characterized in that: Its structural formula is as follows: 。 2. A method for preparing the zwitterionic compound according to claim 1, characterized in that: Includes the following steps: 1) In the presence of a catalyst and a polymerization inhibitor, hydroxyl-containing acrylate compounds and diisocyanate compounds are reacted in an inert atmosphere to obtain isocyanate semi-encapsulated compounds containing urethane acrylates. 2) Under low temperature and inert atmosphere, the isocyanate semi-encapsulated compound containing urethane esters obtained in step 1) is subjected to a nucleophilic addition reaction with a tertiary amine compound containing active hydrogen to obtain an acrylate monomer containing urea group and urethane group. 3) Under an inert atmosphere, the acrylate monomer containing urea and carbamate groups obtained in step 2) reacts with β-propiolactone to obtain a zwitterionic compound containing urea and carbamate groups.

3. The method for preparing the zwitterionic compound as described in claim 2, characterized in that: In step 1), the hydroxyl-containing acrylate compound is one or more of 2-hydroxyethyl acrylate, 4-hydroxybutyl acrylate, and 2-hydroxyethyl methacrylate; Diisocyanate compounds are one or more of hexamethylene diisocyanate, pentamethylene diisocyanate, and isophorone diisocyanate; The catalyst is selected from one or more of dibutyltin dilaurate, stannous octoate, and triethylamine; The polymerization inhibitor is one or more of hydroquinone, p-methoxyphenol, and 2,6-di-tert-butyl-p-cresol; The reaction solvent is an anhydrous solvent, which is one or more of anhydrous acetonitrile, anhydrous toluene, anhydrous chloroform, and anhydrous N,N-dimethylformamide; The molar ratio of hydroxyl-containing acrylate compounds to diisocyanate compounds is 1:1 to 1.3:1; The molar ratio of the total amount of hydroxyl-containing acrylate compounds and diisocyanate compounds to the catalyst is 1:0.01-1:0.05; The molar ratio of hydroxyl-containing acrylate compounds to polymerization inhibitors is 1:0.01-1:0.05; The reaction temperature is 40-80℃, and the reaction time is 1-8 hours; The inert atmosphere is one or both of nitrogen and helium.

4. The method for preparing the zwitterionic compound as described in claim 2, characterized in that: In step 2), the tertiary amine compound containing active hydrogen is one or more of N,N-dimethylethylenediamine, N,N-dimethyl-1,3-propanediamine, and 4-(dimethylamino)butamine; The reaction solvent is an anhydrous solvent, which is one or more of anhydrous dichloromethane, anhydrous chloroform, anhydrous toluene, anhydrous acetonitrile, and anhydrous N,N-dimethylformamide; The molar ratio of the diisocyanate compound to the tertiary amine compound containing active hydrogen in step 1) is 0.7:1 to 1:1; The reaction temperature is 0-10℃, and the reaction time is 0.5-3h; The inert atmosphere is one or both of nitrogen and helium.

5. The method for preparing the zwitterionic compound as described in claim 2, characterized in that: In step 3), the reaction solvent is an anhydrous solvent, which is one or more of anhydrous chloroform, anhydrous dichloromethane, and anhydrous dimethyl sulfoxide. The molar ratio of acrylate monomers containing urea or carbamate groups to β-propiolactone is 1:1 to 1:1.

5. The reaction temperature is 0-25℃, and the reaction time is 17-40h.

6. The application of the zwitterionic compound of claim 1 in the preparation of orthokeratology lenses with antifouling function.

7. A method for preparing an orthokeratology lens with anti-fouling function, characterized in that: Includes the following steps: (1) Mix the monomer, initiator and crosslinking agent. After mixing evenly, add the mixture into the mold and polymerize under ultraviolet light to obtain the corneal reshaping lens substrate. The monomers are methacryloyloxypropyltris(trimethylsiloxane), 1-vinyl-2-pyrrolidone, N,N-dimethylacrylamide and 1,1,1,3,3,3-hexafluoroisopropylisobutylene ester. (2) Dissolve the zwitterionic compound monomer of claim 1 in water to obtain a monomer solution, and add an initiator and a crosslinking agent to it, mix them evenly to obtain a reaction solution; immerse the orthokeratology lens in the reaction solution, and polymerize it under ultraviolet light to obtain an orthokeratology lens with antifouling function.

8. The method for preparing a corneal reshaping lens with anti-fouling function as described in claim 7, characterized in that: In step (1), the initiator is one or both of 2-hydroxy-2-methylphenylacetone and 1-hydroxycyclohexylphenyl ketone; The crosslinking agent is one or both of tetraethylene trimethacrylate and ethylene glycol dimethacrylate; In the total amount of the four monomers—methacryloyloxypropyltris(trimethylsiloxane), 1-vinyl-2-pyrrolidone, N,N-dimethylacrylamide, and 1,1,1,3,3,3-hexafluoroisopropylisobutylenoate—the proportions of methacryloyloxypropyltris(trimethylsiloxane), 1-vinyl-2-pyrrolidone, N,N-dimethylacrylamide, and 1,1,1,3,3,3-hexafluoroisopropylisobutylenoate were 30-35 wt.%, 20-25 wt.%, 10-15 wt.%, and 25-30 wt.%, respectively. The initiator accounts for 0.5-1% wt.% of the total amount of the four monomers; The crosslinking agent accounts for 0.5-2 wt.% of the total amount of the four monomers; When the crosslinking agent is tetraethylene trimethacrylate or ethylene glycol dimethacrylate, the mass ratio of tetraethylene trimethacrylate to tetraethylene trimethacrylate is 0.5:1 to 1.5:1; After mixing thoroughly, sonicate for 1-5 minutes. The wavelength of ultraviolet light is 305-325nm, and the polymerization time is 1-2 hours.

9. The method for preparing a corneal reshaping lens with anti-fouling function as described in claim 7, characterized in that: In step (2), the initiator is one or both of 2-hydroxy-2-methylphenylacetone and 1-hydroxycyclohexylphenyl ketone; The crosslinking agent is one or both of tetraethylene trimethacrylate and ethylene glycol dimethacrylate; The mass ratio of zwitterionic monomer, initiator, and crosslinking agent is 0.02-0.1:0.01-0.02:0.01-0.04; When the crosslinking agent is tetraethylene trimethacrylate or ethylene glycol dimethacrylate, the mass ratio of tetraethylene trimethacrylate to tetraethylene trimethacrylate is 0.5:1 to 1.5:1; The method for achieving uniform mixing is ultrasonic vibration, with a vibration time of 5-15 minutes. Soaking time is 12-36 hours; The wavelength of ultraviolet light is 305-325nm, and the polymerization time is 3-5h.

10. A corneal reshaping lens with anti-fouling function prepared by the preparation method according to any one of claims 7-9.

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