Corneal contact lens with self-healing function and preparation method thereof
By introducing polymers with strong hydrogen bonds and electrostatic interactions into corneal contact lenses to form a self-healing network, the problem of easy damage to orthokeratology lenses is solved, enabling self-healing of scratches, reducing the risk of infection and economic costs, while maintaining lens performance.
Patent Information
- Application Number
- CN202610233847.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-02-27
- Publication Date
- 2026-05-01
AI Technical Summary
Existing orthokeratology lenses are easily damaged during daily care, leading to a high risk of bacterial infection, increased economic costs, and difficulty in maintaining material properties. The damage rate is particularly high among minors, and existing repair technologies are not cost-effective and may affect material safety.
Polymers containing strong intermolecular hydrogen bonding and electrostatic interactions, such as N-(2-amino-2-oxoethyl)acrylamide (NAGA), acrylamide carboxybetaine (CBAA), and acrylate carboxybetaine (ACBMA), are introduced into corneal contact lenses. By irradiating with ultraviolet light, a double non-covalent cross-linked network is formed, enabling scratch self-healing.
Significantly improves lens lifespan, reduces safety risks and economic burden, maintains the optical, mechanical and physicochemical properties of lenses, enables self-repair of scratches, and reduces bacterial hiding and corneal friction damage.
Smart Images
Figure CN121956359A_ABST
Abstract
Description
A self-healing corneal contact lens and its preparation method Technical Field
[0001] This invention belongs to the field of polymer technology, specifically relating to a corneal contact lens with self-healing function and its preparation method. Background Technology
[0002] Myopia has become a global public health challenge. As a region with a high incidence of myopia, my country's data shows that the prevalence of myopia among children and adolescents will climb to 51.9% in 2025. Orthokeratology (Ortho-k) lenses, as an effective current intervention for myopia, can block the pathological elongation of the eye axis, thereby slowing down the progression of myopia.
[0003] Orthokeratology (Ortho-k) lenses are typically made of rigid, highly oxygen-permeable materials such as siloxanes or fluorosilicone acrylates. Because they are worn overnight for extended periods, frequent mechanical cleaning is necessary during routine care. However, improper cleaning can easily lead to micro-damage to the lens surface, with multiple harmful effects: At a microscopic level, scratches can damage the lens surface's smoothness, increasing mechanical friction with the eyelids and cornea, causing foreign body sensation and even corneal epithelial damage; at a biological level, surface defects provide a microenvironment for pathogenic microorganisms to colonize, significantly increasing the probability of infectious complications such as bacterial keratitis; and at an economic level, the high cost of a single pair of Ortho-k lenses means that unplanned replacements will increase the financial burden on families and waste medical resources.
[0004] With the increasing clinical application of orthokeratology (Ortho-k) lenses, a significant proportion of wearers are minors. This group is particularly prone to lens damage due to incomplete fine motor development and difficulties in adherence management. Existing solutions have significant limitations: direct lens replacement is cost-ineffective; conventional polishing only improves superficial imperfections and cannot eliminate deep scratches, and thermochemical treatments may alter the physicochemical properties of the lens materials, posing biosafety risks. As myopia prevention strategies deepen, the industry is demanding higher standards for the safety, functional durability, and health economics of Ortho-k lenses. Developing scratch repair technologies that balance repair efficacy and material compatibility has become an urgent need. Currently, there is insufficient technological reserve in this field; general optical lens repair processes cannot adapt to the rigid materials, high oxygen permeability requirements, and medical-grade biocompatibility standards of Ortho-k lenses, and technological bottlenecks are hindering industry development. Therefore, developing specialized scratch repair technologies tailored to the material characteristics of Ortho-k lenses has significant clinical value and social significance for improving the quality of myopia prevention, reducing medical expenses, and protecting the visual health of adolescents. Summary of the Invention
[0005] The purpose of this invention is to provide a self-healing contact lens and its preparation method. By adding a non-covalent polymer containing strong intermolecular hydrogen bonding and electrostatic interactions to the contact lens, the hydrogen bonding and ionic interactions can drive the movement of the polymer chains, causing the broken molecules in the scratched contact lens to realign and reconnect, thereby restoring the material structure and achieving self-repair of scratches on the contact lens. This effectively solves the problems of bacterial hiding, corneal friction damage, and frequent replacement caused by surface damage in traditional contact lenses, significantly reducing the economic burden while protecting the wearer's eye health.
[0006] To achieve the above objectives, the present invention provides the following technical solution:
[0007] This invention provides a method for preparing a self-healing contact lens, comprising the following steps: dissolving an amphoteric compound in water or a buffer solution, immersing the contact lens in the resulting solution, adding a crosslinking agent and an initiator, mixing well, allowing the solution to stand to allow the amphoteric compound, crosslinking agent, and initiator molecules to be fully distributed in the spatial network of the orthokeratology lens, then polymerizing under ultraviolet light to remove unreacted monomers, and drying to obtain a self-healing contact lens; wherein the amphoteric compound is one or a combination of two or more of N-(2-amino-2-oxoethyl)acrylamide (NAGA), acrylamide carboxybetaine (CBAA), and acrylate carboxybetaine (ACBMA).
[0008] Based on the above technical solution, the crosslinking agent further includes benzophenone (BP), ethylene glycol dimethacrylate (EGDMA), 4-acryloyloxybenzophenone (AOBP), 2,4-bis(trichloromethyl)-6-(4-methoxyphenyl)-S-triazine, polyethylene glycol diacrylate (PEGDA), F127 diacrylate (F127DA), methacrylamide gelatin (GelMA), tetraethylene glycol dimethacrylate (TGDMA), and methacrylamide hyaluronic acid (HAMA); preferably ethylene glycol dimethacrylate (EGDMA) and tetraethylene glycol dimethacrylate (TGDMA).
[0009] Based on the above technical solution, the initiator further includes riboflavin, eosin Y, Irgacure 651, dihydroxydimethylphenylacetone (D-1173), Irgacure 184 and Irgacure 2959; preferably dihydroxydimethylphenylacetone (D-1173) and Irgacure 184.
[0010] Based on the above technical solution, the buffer solution further includes PBS buffer.
[0011] Based on the above technical solution, further, the concentration of the zwitterionic compound is 0.001~0.1g / mL, preferably 0.001~0.05g / mL; the concentrations of the crosslinking agent and the initiator are both 0.001~0.01g / mL, preferably 0.001~0.005g / mL.
[0012] Based on the above technical solution, the standing time is further 6~96 h, preferably 10~48 h, and the temperature of the solution is 10~40℃, preferably 20~30℃.
[0013] Based on the above technical solution, the wavelength of the ultraviolet light is 300~325nm, and the polymerization time is 1~10h, preferably 2~5h.
[0014] Based on the above technical solution, further, the removal of unreacted monomers specifically involves soaking the sample in water for 12-48 hours to remove the unreacted monomers.
[0015] Based on the above technical solution, the corneal contact lens further includes an orthokeratology lens and a corneal bandage lens.
[0016] Based on the above technical solution, the orthokeratology lens further includes synthetic orthokeratology lenses and commercially available orthokeratology lenses.
[0017] Based on the above technical solution, the preparation of acrylamide carboxybetaine (CBAA) further includes the following steps: under inert gas protection and ice-water bath conditions, an organic solvent containing β-propiolactone is added dropwise to an organic solvent containing N-(3-dimethylaminopropyl)acrylamide (DMAPA), the reaction is carried out for 1-6 hours, and then the reaction is carried out at room temperature for 10-24 hours to obtain a white precipitate, which is the final product.
[0018] Based on the above technical solution, the organic solvent is one or a mixture of two of anhydrous acetone and anhydrous tetrahydrofuran. Since a white precipitate is produced, the viscosity of the system will increase as the reaction progresses. Therefore, a low-viscosity solvent is preferred, and anhydrous acetone is preferred.
[0019] Based on the above technical solution, the molar ratio of β-propiolactone to N-(3-dimethylaminopropyl)acrylamide is further 1.5:1 to 1:1, preferably 1.2:1 to 1:1.
[0020] Based on the above technical solution, the preparation of the acrylate carboxybetaine (ACBMA) further includes the following steps: 1) under inert gas protection and with the action of a catalyst and polymerization inhibitor, 2-hydroxyethyl acrylate is reacted with 1,6-hexanediisocyanate to obtain a semi-encapsulated compound containing acrylate isocyanate; 2) under ice bath and inert gas protection, the semi-encapsulated compound containing acrylate isocyanate obtained in step 1) undergoes a nucleophilic addition reaction with N,N-dimethylethylenediamine to obtain an acrylate monomer containing carbamate and urea groups; 3) under inert gas protection, the acrylate monomer containing carbamate and urea groups obtained in step 2) is reacted with β-propiolactone to obtain the zwitterionic monomer ACBMA.
[0021] Based on the above technical solution, further, the catalyst mentioned in step 1) is dibutyltin dilaurate, the molar ratio of 2-hydroxyethyl acrylate to 1,6-hexanediisocyanate is 1.3:1 to 1:1, preferably 1.2:1 to 1:1, and the molar ratio of 2-hydroxyethyl acrylate to the catalyst is 1:0.01 to 1:0.05, preferably 1:0.01 to 1:0.03.
[0022] Based on the above technical solution, further, the reaction temperature in step 1) is 30~70℃, preferably 40~60℃; the reaction time is 0.5~6h, preferably 1~4h.
[0023] Based on the above technical solution, further, the polymerization inhibitor mentioned in step 1) is hydroquinone or p-methoxyphenol, preferably p-methoxyphenol, and the molar ratio of 2-hydroxyethyl acrylate to the polymerization inhibitor is 1:0.01~1:0.05, preferably 1:0.01~1:0.03.
[0024] Based on the above technical solution, further, in step 2), the molar ratio of the semi-encapsulated compound containing acrylate isocyanate to N,N-dimethylethylenediamine is 0.7:1 to 1:1, preferably 0.8:1 to 1:1.
[0025] Based on the above technical solution, further, in step 2), the reaction temperature is 0~10℃, preferably 0~8℃, and the reaction time is 0.5~4h, preferably 0.5~2h.
[0026] Based on the above technical solution, further, in step 3), the reaction temperature is 0~10℃, preferably 0~8℃, the reaction time is 16~36h, preferably 24~36h, the reaction solvent is anhydrous chloroform or anhydrous dichloromethane, preferably anhydrous dichloromethane; the molar ratio of β-propiolactone to acrylate monomers containing carbamate and urea groups is 3:1~1:1, preferably 2:1~1:1.
[0027] Based on the above technical solution, the synthesis method of the synthesized orthokeratology lens further includes the following steps: Methacryloxypropyltris(trimethylsiloxane)silane (TRIS), N,N-dimethylformamide (DMA), N-vinylpyrrolidone (NVP), and 1,1,1,3,3,3-hexafluoroisopropylisobutylene ester (HFMA) are added to an organic solvent in a mass ratio of 30~40:15~25:10~20:25~35. An initiator and crosslinking agent are added, the mixture is stirred, and after degassing, it is poured into an orthokeratology lens mold and polymerized under ultraviolet light for 0.5~3 hours. After demolding, the lens is immersed in a 40~60% ethanol aqueous solution for 8~36 hours to remove unreacted monomers and initiator. Then, the resulting lens is immersed in ultrapure water for 8~36 hours to remove ethanol, thus obtaining the final product.
[0028] Based on the above technical solution, further, the organic solvent includes n-butanol, the monomer concentration is 0.5~1.5g / mL, the crosslinking agent includes ethylene glycol dimethacrylate (EGDMA) and tetraethylene glycol dimethacrylate (TGDMA); the initiator is dihydroxydimethylacetone (D-1173); the amount of initiator and crosslinking agent added is 0.1~1.0wt% of the total monomer mass, the wavelength of ultraviolet light is 300~325nm, preferably 305nm, and the polymerization time is 1~2h, preferably 1h.
[0029] Based on the above technical solution, the method for synthesizing the corneal bandage lens further includes the following steps: Methacryloxypropyltris(trimethylsiloxane)silane (TRIS), N-vinylpyrrolidone (NVP), hydroxyethyl methacrylate (HEMA), and N,N-dimethylformamide (DMA) are added to an organic solvent in a mass ratio of 40~60:5~15:5~15:25~35; an initiator and a crosslinking agent are added, the mixture is stirred, and after degassing, it is poured into a corneal bandage lens mold and polymerized under ultraviolet light for 0.5~3 hours; after demolding, the lens is immersed in a 40~60% ethanol aqueous solution for 8~36 hours to remove unreacted monomers and initiators; then, the resulting lens is immersed in ultrapure water for 8~36 hours to remove ethanol, thus obtaining the final product.
[0030] Based on the above technical solution, further, the organic solvent includes n-butanol, the monomer concentration is 0.5~1.5g / mL, the crosslinking agent includes ethylene glycol dimethacrylate (EGDMA) and tetraethylene glycol dimethacrylate (TGDMA); the initiator is dihydroxydimethylacetone (D-1173); the amount of initiator and crosslinking agent added is 0.1~1.0wt% of the total monomer mass, the wavelength of ultraviolet light is 300~325nm, preferably 305nm, and the polymerization time is 1~2h, preferably 1h.
[0031] The present invention also provides a corneal contact lens with self-healing function prepared by the above-described preparation method.
[0032] Compared with existing technologies, this invention has the following beneficial effects: 1. This application endows orthokeratology lenses with excellent self-healing properties, significantly extending the lens lifespan and reducing safety risks: By introducing N-acetylglucosamine acrylamide (NAGA) with strong hydrogen bonding and carboxybetaine monomers (CBAA / ACBMA) with electrostatic interactions, a dual non-covalent cross-linked network is constructed in the lens material. This design increases the scratch healing rate of the material to 15.30% (pore volume) in air environment after 24 hours, and further increases the healing rate to 73.04% in borate-borax buffer (pH=7.4). The synergistic effect of hydrogen bonding and ionic interactions drives polymer chain movement and recombination, realizing the self-repair of scratches, effectively solving the problems of bacterial hiding, corneal friction damage, and frequent replacement caused by surface damage in traditional orthokeratology lenses, and significantly reducing the economic burden while protecting the wearer's eye health.
[0033] 2. This application achieves self-healing functionality while fully maintaining the key clinical application performance of orthokeratology lenses: the modified lens material meets medical standards in terms of optical, mechanical, and physicochemical properties: visible light transmittance is maintained above 80%, ensuring visual clarity; water content (EWC < 6%) and equilibrium swelling ratio (SR < 7%) are controlled at low levels to avoid excessive tear absorption and dry eye syndrome; Shore hardness (D) is maintained within the range of 73-76, balancing shaping effectiveness and wearing comfort; flexural modulus (950 MPa) and compressive modulus (2.7 GPa) are significantly improved compared to the matrix material, enhancing structural stability. This fabrication process anchors functional monomers to the matrix network through ultraviolet photopolymerization, introducing dynamic non-covalent bonds without sacrificing the rigid framework properties of the material, thus achieving a balance between self-healing function and clinical applicability. Attached Figure Description
[0034] To more clearly illustrate the embodiments of the present invention, the accompanying drawings involved in the embodiments will be briefly described below.
[0035] Figure 1: Schematic diagram of the preparation of the orthokeratology lens in Example 1.
[0036] Figure 2: Preparation and characterization diagram of CBAA in Example 2, where A) is a schematic diagram of CBAA preparation, B) is the 1H NMR spectrum of CBAA, and C) is the mass spectrometry characterization diagram of CBAA.
[0037] Figure 3: Schematic diagram of the preparation of ACBMA in Example 3.
[0038] Figure 4: Characterization diagram of AMA in Example 3, where A) is the 1H NMR spectrum of AMA and B) is the mass spectrometry characterization diagram of AMA.
[0039] Figure 5: Characterization diagram of ACBMA in Example 3, where A) is the 1H NMR spectrum of ACBMA and B) is the mass spectrometry characterization diagram of ACBMA.
[0040] Figure 6: Static water contact angle (A), light transmittance (B), equilibrium water content (C), and anti-swelling performance (D) of the corneal reshaping lenses before and after modification in Examples 4-5.
[0041] Figure 7: Mechanical properties of the orthokeratology lens before and after modification in Example 5. In Figure 7, A) shows the hardness of the orthokeratology lens tested by a Shore D hardness tester; B)-D) show the bending stress, bending modulus and compression modulus of the orthokeratology lens tested by a universal testing machine.
[0042] Figure 8: The effect of scratch repair before and after corneal reshaping lens modification observed by material confocal microscope in Example 6. In this figure, A) is the repair rate of the material in air and the optical image of the repair; B) is the repair rate of the material immersed in the repair agent and the optical image of the repair.
[0043] Figure 9: Scratch repair results of commercially available orthokeratology lenses modified with ACBMA in Example 7 in the repair agent BABS, where A) is a Mulikang brand orthokeratology lens, B) is a Punotong brand orthokeratology lens, and C) is an eyekan brand orthokeratology lens.
[0044] Figure 10: Comparison of scratch depth fluctuations before and after repair in BABS with the ACBMA-modified corneal bandage lens in Example 8. Detailed Implementation
[0045] The present invention will be described in detail below with reference to the embodiments. However, the implementation of the present invention is not limited thereto. Obviously, the embodiments described below are only some embodiments of the present invention. For those skilled in the art, other similar embodiments can be obtained without creative effort and all fall within the protection scope of the present invention.
[0046] The main reagents used in the examples are as follows: 1. NAGA: N-(2-amino-2-oxoethyl)acrylamide, Aladdin Holdings Group Co., Ltd.; 2. HEA: Hydroxyethyl acrylate, Aladdin Holdings Group Co., Ltd.; 3. HDI: Hexamethylene diisocyanate, Beijing Innocare Technology Co., Ltd.; 4. DMEDA: N,N-dimethylethylenediamine, Beijing Innocare Technology Co., Ltd.; 5. BPL: β-propiolactone, Beijing Innocare Technology Co., Ltd.; 6. DBTDL: Dibutyltin dilaurate, Beijing Innocare Technology Co., Ltd.; 7. MEHQ: 4-methoxyphenol, Aladdin Holdings Group Co., Ltd.; 8. DMAPA: N-(3-dimethylaminopropyl)acrylamide, Beijing Innocare Technology Co., Ltd.; 9. TRIS: Methacryloxypropyltris(trimethylsiloxane), purchased from Shanghai Maclean Biochemical Technology Co., Ltd.; 10. NVP: N-vinylpyrrolidone, purchased from Shanghai Maclean Biochemical Technology Co., Ltd.; 11. DMA: N,N-dimethylformamide, purchased from Aladdin Reagent (Shanghai) Co., Ltd.; 12. HFMA: 1,1,1,3,3,3-hexafluoroisopropyl isobutylene ester, purchased from Shanghai Maclean Biochemical Technology Co., Ltd.; 13. EGDMA: ethylene glycol dimethacrylate, purchased from Aladdin Reagent (Shanghai) Co., Ltd.; 14. TGDMA: tetraethylene trimethacrylate, purchased from Aladdin Reagent (Shanghai) Co., Ltd.; 15. D-1173: 2-hydroxy-2-methylphenylacetone, purchased from Aladdin Reagent (Shanghai) Co., Ltd.; 16. HEMA: hydroxyethyl methacrylate, purchased from Aladdin Reagent (Shanghai) Co., Ltd.; 17. Preparation of boric acid and borax solution (pH=7.4): 45 mL of boric acid aqueous solution (0.2 M) + 5 mL of borax aqueous solution (0.05 M) were mixed to prepare 50 mL of buffer solution with pH=7.4. Both boric acid and borax salt were purchased from Aladdin Reagent (Shanghai) Co., Ltd.
[0047] Example 1: First, an orthokeratology lens was prepared, including the following steps: 0.35 g TRIS, 0.20 g DMA, 0.15 g NVP, and 0.30 g HFMA were dissolved in 1 mL n-butanol. Then, crosslinking agents EGDMA, TGDMA, and photoinitiator D-1173 were added, each at 0.5 wt% of the total monomer mass. After mixing, the solution was sonicated at room temperature for 30 min, then poured into a contact lens mold and polymerized under ultraviolet light (305 nm) for 1 hour. After demolding, the lens was immersed in a 50% ethanol aqueous solution (v / v) for 12 hours to remove unreacted monomers and initiators. Then, the resulting lens was immersed in ultrapure water for 12 hours to remove ethanol. Finally, the obtained orthokeratology lens was stored in phosphate buffer solution (PBS, pH=7.4) at room temperature. The resulting orthokeratology lens is denoted as HG.
[0048] The corneal bandage lens was prepared as follows: 0.5 g TRIS, 0.10 g NVP, 0.10 g HEMA, 0.30 g DMA, 0.007 g EGDMA, and 0.003 g D-1137 were dissolved in 1 mL n-butanol. The resulting mixture was sonicated at room temperature for 30 min, then poured into a contact lens mold and polymerized under ultraviolet light (305 nm) for 1 hour. After demolding, the resulting lens was immersed in 50% ethanol aqueous solution (v / v) for 12 hours to remove unreacted monomers and initiators. The lens was then immersed in ultrapure water for 12 hours to remove ethanol. Finally, the corneal bandage lens was stored in phosphate-buffered saline (PBS, pH=7.4) at room temperature. The prepared corneal bandage lens is denoted as CL.
[0049] Specific descriptions of different commercially available orthokeratology lenses: iBright – Aibonod (Beijing) Medical Technology Co., Ltd.; Material: Fluorosilicone acrylate polymer; Oxygen permeability: DK 125×10 -11 (cm 2 / s)[mlO2 / (ml×mmHg)]; Menicon – Menicon Corporation, Japan; Material: Self-developed ZOMA ultra-high oxygen permeable fluorosilicone acrylate; Oxygen permeability coefficient: DK 163×10 -11 (cm 2 / s)[mlO2 / (ml×mmHg)]; Eyekan; Material: High oxygen permeable fluorosilicone acrylate; Oxygen permeability coefficient: DK 100×10 -11 (cm 2 / s)[mlO2 / (ml×mmHg)].
[0050] In Example 2, 6.0 g of DMAPA (51.2 mmol) was dissolved in 30 mL of anhydrous acetone, and then 4.0 g of β-propiolactone (55.6 mmol) was dissolved in 30 mL of acetone. The β-propiolactone acetone solution was slowly added dropwise to the DMAPA acetone solution under ice-water bath conditions (6 °C). After reacting for 4 h, the mixture was stirred at room temperature for 20 h under nitrogen protection. After the reaction was complete, a white precipitate was obtained by filtration. After washing three times with anhydrous acetone, the precipitate was dried under vacuum to obtain a white product, which was acrylamide carboxybetaine (CBAA) monomer. The structure was confirmed by NMR and mass spectrometry (Figure 2), with a yield of 80.2%.
[0051] In Example 3, under light-protected conditions and a nitrogen atmosphere, 1,6-hexamethylene diisocyanate (2.1023 g, 12.5 mmol), anhydrous acetonitrile (10 mL), polymerization inhibitor p-methoxyphenol (MEHQ, 0.0125 g), and catalyst dibutyltin dilaurate (DBTDL, 5 mg (5 μL)) were placed in a round-bottom flask and stirred for 10 minutes. After the temperature of the reaction solution was raised to 40 °C, 2-hydroxyethyl acrylate (1.4515 g, 12.5 mmol) was dissolved in 5 mL of anhydrous acetonitrile and slowly added dropwise to the above reaction solution. Then the temperature was slowly raised to 60 °C. After 1 hour, a clear and transparent solution was obtained (Figure 3).
[0052] Then, under nitrogen and ice bath conditions (temperature 6℃), an anhydrous acetonitrile solution of N,N-dimethylethylenediamine (1.1019 g, 12.5 mmol) was added dropwise to the above clear and transparent solution. The addition was completed in about 15 min, and 30 mL of anhydrous acetonitrile was added in the middle (to increase viscosity, the solvent was in excess, and the mixture was stirred thoroughly) to obtain a white solid. The reaction was carried out in an ice bath for 30 min, filtered, washed three times with anhydrous acetonitrile, and dried under vacuum at 35℃ for 24 h to obtain a white solid. The yield was 73%, which is the AMA monomer. The structure was confirmed by NMR and mass spectra (Figure 4).
[0053] Finally, under light-protected conditions and a nitrogen atmosphere, 1.1167 g (3 mmol) of the white solid obtained above was dissolved in 20 mL of anhydrous dichloromethane, and 0.4324 g (6 mmol) of β-propiolactone was dissolved in 5 mL of anhydrous dichloromethane. Under ice bath conditions, the dichloromethane solution of β-propiolactone was slowly added dropwise to the above solution. The reaction was carried out in an ice bath for 2 h, stirred at room temperature for 22 h, and centrifuged to obtain a colorless oily substance. The substance was washed three times with anhydrous dichloromethane, water was added, washed, centrifuged, and freeze-dried. The colorless oily viscous substance was the ACBMA monomer, and its structure was confirmed by NMR and mass spectra (Figure 5).
[0054] Example 4: Preparation of a self-healing orthokeratology lens: Take 0.08 g of NAGA monomer, add 5 mL of deionized water, immerse the orthokeratology lens prepared in Example 1 in the above monomer solution, add 0.01 g of photoinitiator (D-1173), and 0.01 g each of crosslinking agents (EGDMA, TGDMA), sonicate for 1 min, and let stand at room temperature for 24 h (to allow the monomer, initiator, and crosslinking agent to fully enter the pores of the orthokeratology lens). Then, polymerize the mixed solution containing the orthokeratology lens under ultraviolet (305 nm) light for 3 h to obtain a double-network orthokeratology lens. Immerse it in water for 24 h (to remove unreacted monomer, crosslinking agent, and initiator), change the water every 6 hours, and vacuum dry at 40°C for 24 h to obtain a dried orthokeratology lens, denoted as pNAGA-HG.
[0055] Take 0.02 g of CBAA monomer and add 5 mL of deionized water. Immerse the orthokeratology lens prepared in Example 1 in the monomer solution. Add 0.01 g of photoinitiator (D-1173) and 0.01 g each of crosslinking agents (EGDMA and TGDMA). Sonicate for 1 min and let stand at room temperature for 24 h (allowing the monomer, initiator, and crosslinking agent to fully penetrate the pores of the orthokeratology lens). Then, polymerize the mixed solution containing the orthokeratology lens under ultraviolet (305 nm) light for 3 h to obtain a double-network orthokeratology lens. Immerse it in water for 24 h (to remove unreacted monomer, crosslinking agent, and initiator), changing the water every 6 hours. Vacuum dry at 40℃ for 24 h to obtain a dried orthokeratology lens, denoted as pCBAA-HG.
[0056] Take 0.02g of CBAA monomer and 0.08g of NAGA monomer, add 5mL of deionized water, and immerse the orthokeratology lens prepared in Example 1 in the above monomer solution. Add 0.01g of photoinitiator (D-1173) and 0.01g each of crosslinking agents (EGDMA and TGDMA), sonicate for 1min, and let stand at room temperature for 24h (to allow the monomers, initiator, and crosslinking agents to fully penetrate into the pores of the orthokeratology lens). Then, polymerize the mixed solution containing the orthokeratology lens under ultraviolet (305 nm) light for 3h to obtain a double-network orthokeratology lens. Immerse it in water for 24h (to remove unreacted monomers, crosslinking agents, and initiators), changing the water every 6 hours. Vacuum dry at 40℃ for 24h to obtain a dried orthokeratology lens, denoted as pNAGA-pCBAA-HG.
[0057] Take 0.08 g of ACBMA monomer and add 5 mL of deionized water. Immerse the orthokeratology lens prepared in Example 1 in the monomer solution. Add 0.01 g of photoinitiator (D-1173) and 0.01 g each of crosslinking agents (EGDMA and TGDMA). Sonicate for 1 min and let stand at room temperature for 24 h (allowing the monomer, initiator, and crosslinking agent to fully penetrate the pores of the orthokeratology lens). Then, polymerize the mixed solution containing the orthokeratology lens under ultraviolet (305 nm) light for 3 h to obtain a double-network orthokeratology lens. Immerse it in water for 24 h (to remove unreacted monomer, crosslinking agent, and initiator), changing the water every 6 hours. Vacuum dry at 40℃ for 24 h to obtain a dried orthokeratology lens, denoted as pACBMA-HG.
[0058] The water contact angle change of the obtained corneal reshaping lens was measured using a static water contact angle measuring instrument. Specifically, a dry rectangular sample with dimensions of 10 mm in length, 10 mm in width, and 3 mm in thickness was placed on the static water contact angle measuring instrument, and a drop of ultrapure water was dropped onto the sample using a 50 μL syringe. The water contact angle change of the sample surface was measured using the five-point fitting method.
[0059] The water contact angle test results are shown in Figure 6A. The water contact angle of the modified orthokeratology lens is distributed in the range of 65°-78°, while the measured value of the untreated control group orthokeratology lens HG is 92°. The results show that after the addition of NAGA, CBAA, and ACBMA monomers for polymerization, the static water contact angle of the orthokeratology lens is slightly reduced. The results indicate that CBAA, NAGA, and ACBMA are combined with HG, and the change in wettability proves that the material modification is successful.
[0060] Example 5: Good optical transmittance is an important indicator for orthokeratology lenses. In this example, an ultraviolet spectrophotometer was used to detect the transmittance of dried HG, pCBAA-HG, pNAGA-HG, pNAGA-pCBAA-HG, and pACBMA-HG in the visible light range.
[0061] The results are shown in Figure 6B. The results show that the light transmittance of all orthokeratology lenses is above 80%, which is good. This indicates that the processing technology can meet the requirements for the use of orthokeratology lenses.
[0062] As a rigid material, orthokeratology lenses should maintain a low water content. A high water content (EWC) will cause the lens to absorb water from the tears, which can lead to problems such as dry eyes. In addition, in order to ensure that the lens maintains a fixed shape, it should maintain good anti-swelling properties.
[0063] This embodiment also tested the equilibrium water content (EWC) and equilibrium swelling ratio (SR) of dried HG, pCBAA-HG, pNAGA-HG, pNAGA-pCBAA-HG, and pACBMA-HG prepared in Example 4.
[0064] The results are shown in Figures 6C-D. The EWC of all orthokeratology lens materials was less than 6%, and the equilibrium swelling ratio (SR) of all orthokeratology lens materials was less than 7%, demonstrating good anti-swelling performance.
[0065] In addition, orthokeratology lenses must meet certain hardness requirements to achieve the desired reshaping effect. Excessive hardness reduces patient comfort and affects the lens's fit to the patient's ocular surface, while insufficient hardness may fail to meet the reshaping requirements, thus reducing the effectiveness of myopia correction. This embodiment uses the Shore D hardness test (testing standard GB / T 531-1999) to evaluate the impact of CBAA, NAGA, and ACBMA modifications in Example 4 on lens structural stability. Test samples were prepared with a thickness of at least 6 mm, a test area at least 12 mm from the edge, and a smooth surface. Readings were taken within 1 second after pressure foot contact. The test results are shown in Figure 7A. The results show a hardness between 73 and 76 D, indicating that the hardness of HG, pCBAA-HG, pNAGA-HG, pNAGA-pCBAA-HG, and pACBMA-HG all meet the requirements.
[0066] The bending and compression properties of HG, pCBAA-HG, pNAGA-HG, pNAGA-pCBAA-HG, and pACBMA-HG prepared in Example 4 were measured using a universal testing machine. The samples were tested at room temperature. For bending, a dried rectangular strip with a length of 80 mm, a width of 15 mm, and a height of 4 mm was prepared and placed on the universal testing machine using a three-point bending test apparatus. The sample was then broken, and the elastic modulus of bending was calculated using load-displacement curves. For compression, a dried cylinder with a height of 6 mm and a diameter of 10 mm was prepared and placed on the universal testing machine. The sample was compressed to 0.6 mm, and the elastic modulus of compression was obtained by calculating the slope of the load at 85%-90% strain.
[0067] The compressive properties of the modified orthokeratology lens from Example 4 were investigated using a universal testing machine. Compression tests were conducted at room temperature using an Instron 5543A universal testing machine (Instron Corporation, Norwood, Massachusetts) equipped with an 800 kN load sensor. The sample dimensions were 10 mm in diameter and 5 mm in thickness. The crosshead speed of the universal testing machine was set to 2 mm / min. Compression fracture stress, fracture strain, elastic modulus, and toughness parameters were extracted from the stress-strain curves obtained from at least three independent tests. The compressive modulus at 5%-10% compressive strain was calculated based on the initial slope of the stress-strain curve within the 5-10% strain range.
[0068] The results are shown in Figures 7B-D. The results show that after the addition of NAGA, CBAA, and ACBMA for polymerization, the flexural modulus of the orthokeratology lens samples increased from 800 MPa to 950 MPa, and the compressive modulus increased from 2.5 GPa to 2.7 GPa. This indicates that the addition of NAGA, CBAA, and ACBMA for polymerization resulted in an appropriate increase in the mechanical strength of the orthokeratology lens material.
[0069] Example 6: Evaluation of the self-healing function of orthokeratology lenses: HG, pCBAA-HG, pNAGA-HG, pNAGA-pCBAA-HG, and pACBMA-HG prepared in Example 4 were prepared into dried rectangular strips with a length of 10 mm, a width of 10 mm, and a thickness of 3 mm. These strips were placed in a bio-nano-scratching instrument, and scratches were applied using a force of 60 mN to obtain scratch models with a length of 250 μm. These models were then observed under a material-type laser confocal microscope, and the average pore volume was calculated. The average pore volumes of the scratches on HG, pCBAA-HG, pNAGA-HG, pNAGA-pCBAA-HG, and pACBMA-HG prepared in Example 4 were 4452.17 ± 692.72 μm and 4475 ± 153 μm, respectively. 3 4572±365μm 3 4690±107μm 3 4839±384μm 3 The obtained scratched samples were placed in the air at room temperature (25℃) for 0h, 1h, 16h, and 24h, and the changes in the pore volume of the scratches were photographed at different time periods (0h, 1h, 16h, and 24h) to evaluate the healing rate of the material.
[0070] Evaluation of the self-healing function of orthokeratology lenses: HG, pCBAA-HG, pNAGA-HG, pNAGA-pCBAA-HG, and pACBMA-HG prepared in Example 4 were prepared into dried rectangular strips with a length of 10 mm, a width of 10 mm, and a thickness of 3 mm. These strips were placed in a bio-nano-scratcher and scratched with a force of 60 mN, resulting in a scratch model with a length of 250 μm. The model was then observed under a material-based laser confocal microscope, and the average pore volumes were 4452.17 ± 692.72 μm and 4475 ± 153 μm, respectively. 3 4572±365μm 3 4690±107μm 3 4839±384μm 3 The obtained scratched samples were placed in a borate-borax buffer solution at pH 7.4 at room temperature (25°C) for 0h, 1h, 16h, and 24h. The changes in pore volume of the scratches in the healing solution (borate-borax buffer solution) at different time periods (0h, 1h, 16h, and 24h) were photographed to evaluate the healing rate of the material.
[0071] The results are shown in Figure 8. Without a healing solution, the pore volume healing rate of HG after 24 hours was 2.58%. After polymerization with NAGA and CBAA, the pore volume healing rate reached a maximum of 11.31% after 24 hours. After polymerization with ACBMA, the pore volume healing rate reached a maximum of 15.30% after 24 hours, indicating that the addition of NAGA and CBAA can effectively improve the healing rate. With a healing solution (borate-borax buffer solution at pH 7.4), the pore volume healing rate of HG after 24 hours was 50.65%. After polymerization with NAGA and CBAA, the pore volume healing rate reached a maximum of 70.39% after 24 hours. After polymerization with ACBMA, the pore volume healing rate reached a maximum of 73.04% after 24 hours. These results indicate that adding non-covalent compounds containing strong intermolecular hydrogen bonding and electrostatic interactions can effectively improve the self-healing effect of the material. Hydrogen bonding and ionic interactions can drive the movement of polymer chains, causing broken molecules to realign and reconnect, thereby restoring the material's structure.
[0072] Example 7: Take 0.08g of ACBMA monomer and add 5mL of deionized water. Soak the Mulikang brand orthokeratology lens in the monomer solution. Add 0.01g of photoinitiator (D-1173) and 0.01g each of crosslinking agents (EGDMA and TGDMA). Sonicate for 1 minute and let stand at room temperature for 24 hours (to allow the monomer, initiator, and crosslinking agent to fully enter the pores of the orthokeratology lens). Then, polymerize the mixed solution containing the orthokeratology lens under ultraviolet (305 nm) light for 3 hours to obtain a double-network orthokeratology lens. Soak it in water for 24 hours (to remove unreacted monomer, crosslinking agent, and initiator). Change the water every 6 hours and vacuum dry at 40°C for 24 hours to obtain a dried orthokeratology lens.
[0073] First, a scratch model was established on the surface of ACBMA-modified Mulikang brand orthokeratology lens material using a nanoindenter under a constant force of 60 mN. The average pore volume was 2032.18 μm. 3 Commercially available orthokeratology lenses modified with ACBMA and indented with scratches were immersed in a borate-borax solution (BABS) at 25°C for 120 h. A scratch model was then created on the surface of unmodified Mulikang brand orthokeratology lenses using a nanoindenter under a constant force of 60 mN, with an average pore volume of 1827 μm. 3 The experiment in which the scratched orthokeratology lenses of the brand "Milikang" were immersed in BABS under the same experimental conditions served as a control.
[0074] The experimental results are shown in Figure 9A. The results indicate that the repair rate of the ACBMA-modified Mulikang orthokeratology lens after 120 hours in the repair solution was 10.59%, significantly higher than the control repair rate (2.31%). Normalization of the repair rate showed that the repair rate of the ACBMA-modified Mulikang orthokeratology lens after 120 hours in the repair solution was approximately 4.5 times that of the control (immersed in BABS), demonstrating a significant improvement in repair effectiveness.
[0075] Take 0.08g of ACBMA monomer and add 5mL of deionized water. Immerse the ProPure brand orthokeratology lens in the monomer solution. Add 0.01g of photoinitiator (D-1173) and 0.01g each of crosslinking agents (EGDMA and TGDMA). Sonicate for 1 minute and let stand at room temperature for 24 hours (allowing the monomer, initiator, and crosslinking agent to fully penetrate the pores of the orthokeratology lens). Then, polymerize the mixture containing the orthokeratology lens under ultraviolet (305 nm) light for 3 hours to obtain a double-network orthokeratology lens. Immerse it in water for 24 hours (to remove unreacted monomer, crosslinking agent, and initiator), changing the water every 6 hours. Vacuum dry at 40℃ for 24 hours to obtain a dried orthokeratology lens.
[0076] A scratch model was established on the surface of ACBMA-modified PunoTong orthokeratology lens material using a nanoindenter under a constant force of 60 mN. The average pore volume was 2189.85 μm. 3 The ACBMA-modified orthokeratology lenses with indented scratches were immersed in BABS at 25°C for 120 h, followed by immersion in a repair solution. A scratch model was then created on the surface of unmodified ProPure brand orthokeratology lenses using a nanoindenter under a constant force of 60 mN, with an average pore volume of 1901.36 μm. 3 The experiment in which the Puno Tong brand orthokeratology lenses with scratches were immersed in BABS under the same experimental conditions served as a control.
[0077] The results are shown in Figure 9B. The results indicate that the repair rate of the ACBMA-modified PunoTong orthokeratology lens after 120 h in the repair solution was 13.12%, significantly higher than the control repair rate (3.87%). Normalization of the repair rate showed that the repair rate of the ACBMA-modified PunoTong orthokeratology lens after 120 h in the repair solution was approximately 3.4 times that of the control (immersed in PBS), demonstrating a significant improvement in repair effectiveness.
[0078] Take 0.08g of ACBMA monomer and add 5mL of deionized water. Immerse the Puyekan brand orthokeratology lens in the monomer solution. Add 0.01g of photoinitiator (D-1173) and 0.01g each of crosslinking agents (EGDMA and TGDMA). Sonicate for 1 minute and let stand at room temperature for 24 hours (allowing the monomer, initiator, and crosslinking agent to fully penetrate the pores of the orthokeratology lens). Then, polymerize the mixture containing the orthokeratology lens under ultraviolet (305 nm) light for 3 hours to obtain a double-network orthokeratology lens. Immerse it in water for 24 hours (to remove unreacted monomer, crosslinking agent, and initiator), changing the water every 6 hours. Vacuum dry at 40℃ for 24 hours to obtain a dried orthokeratology lens.
[0079] A scratch model was established on the surface of ACBMA-modified eyekan orthokeratology lens material using a nanoindenter under a constant force of 60 mN. The average pore volume was 2107.43 μm. 3 The ACBMA-modified orthokeratology lenses with indentations were immersed in BABS solution at 25°C, followed by immersion in a repair solution for 120 h. A scratch model was then created on the surface of unmodified eyekan orthokeratology lenses using a nanoindenter under a constant force of 60 mN, with an average pore volume of 1856 μm. 3 The experiment in which the eyekan brand orthokeratology lenses with indentations were immersed in BABS under the same experimental conditions served as a control.
[0080] The results are shown in Figure 9C. The results indicate that the repair rate of the ACBMA-modified eyekan orthokeratology lens after 120 hours in the repair solution was 30.49%, significantly higher than the control repair rate (6.53%). Normalization of the repair rate showed that the repair effect of the ACBMA-modified eyekan orthokeratology lens after 120 hours in the repair solution was approximately 4.6 times that of the control (immersed in BABS), demonstrating a significant improvement in repair performance.
[0081] In Example 8, 0.08 g of ACBMA monomer was added to 5 mL of deionized water. The corneal bandage lens (CL) prepared in Example 1 was immersed in the monomer solution. 0.01 g of photoinitiator (D-1173) and 0.01 g each of crosslinking agents (EGDMA and TGDMA) were added. The mixture was ultrasonically vibrated for 1 min and allowed to stand at room temperature for 24 h (to allow the monomer, initiator, and crosslinking agent to fully penetrate the pores of the corneal reshaping lens). The mixed solution containing the corneal reshaping lens was then polymerized under ultraviolet (305 nm) light for 3 h to obtain a double-network corneal reshaping 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 then vacuum dried at 40°C for 24 h to obtain a dried corneal reshaping lens.
[0082] A scratch model was established on the surface of an ACBMA-modified corneal bandage lens (CL) using a nanoindenter under a constant force of 60 mN, with an average pore volume of 4257 μm. 3 The CL material with indented scratches was immersed in BABS at 25°C, and the corneal bandage lens was immersed in the repair solution for 120 h. A scratch model was established on the surface of the corneal bandage lens (CL) prepared in Example 1 using a nanoindenter under a constant force of 60 mN, with an average pore volume of 3829 μm. 3 A control experiment was conducted by immersing corneal bandage lenses (CLs) with indentations in BABS under the same experimental conditions. The repair effect of the material was calculated by measuring the change in scratch hole depth using a material confocal microscope. The results showed that the repair rate of the ACBMA-modified corneal bandage lens was 81.32%, which was a surprising improvement compared to the control (repair rate of 16.24%). The scratch depth of the ACBMA-modified corneal bandage lens decreased from 1.33 μm to 0.31 μm before and after immersion, a reduction of 4.29 times (Figure 10).
[0083] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.
Claims
1. A method for preparing a corneal contact lens with self-healing function, characterized in that, The process includes the following steps: dissolving an amphoteric compound in water or a buffer solution, immersing a corneal contact lens in the resulting solution, adding a crosslinking agent and an initiator, mixing well, allowing the mixture to stand to allow the amphoteric compound, crosslinking agent, and initiator molecules to be fully distributed in the spatial network of the corneal reshaping lens, then polymerizing under ultraviolet light to remove unreacted monomers, and drying to obtain a corneal contact lens with self-healing function; the amphoteric compound is one or a combination of two or more of N-(2-amino-2-oxoethyl)acrylamide (NAGA), acrylamide carboxybetaine (CBAA), and acrylate carboxybetaine (ACBMA).
2. The preparation method according to claim 1, characterized in that, The crosslinking agents include benzophenone (BP), ethylene glycol dimethacrylate (EGDMA), 4-acryloyloxybenzophenone (AOBP), 2,4-bis(trichloromethyl)-6-(4-methoxyphenyl)-S-triazine, polyethylene glycol diacrylate (PEGDA), F127 diacrylate (F127DA), methacrylamide gelatin (GelMA), tetraethylene glycol dimethacrylate (TGDMA), and methacrylamide hyaluronic acid (HAMA); preferably ethylene glycol dimethacrylate (EGDMA) and tetraethylene glycol dimethacrylate (TGDMA); the initiators include riboflavin, eosin Y, Irgacure 651, dihydroxydimethylphenylacetone (D-1173), Irgacure 184, and Irgacure 2959; preferably dihydroxydimethylphenylacetone (D-1173) and Irgacure 184; the buffer solution includes PBS buffer.
3. The preparation method according to claim 1, characterized in that, The concentration of the zwitterionic compound is 0.001~0.1 g / mL, preferably 0.001~0.05 g / mL; the concentrations of the crosslinking agent and the initiator are both 0.001~0.01 g / mL, preferably 0.001~0.005 g / mL; the standing time is 6~96 h, preferably 10~48 h; the solution temperature is 10~40℃, preferably 20~30℃; the wavelength of the ultraviolet light is 300~325 nm; and the polymerization time is 1~10 h, preferably 2~5 h.
4. The preparation method according to claim 1, characterized in that, The corneal contact lenses include orthokeratology lenses and corneal bandage lenses; the orthokeratology lenses include synthetic orthokeratology lenses and commercially available orthokeratology lenses.
5. The preparation method according to claim 1, characterized in that, The preparation of the acrylamide carboxybetaine (CBAA) includes the following steps: under inert gas protection and ice-water bath conditions, an organic solvent containing β-propiolactone is added dropwise to an organic solvent containing N-(3-dimethylaminopropyl)acrylamide (DMAPA), and the reaction is carried out for 1-6 hours. Then, the reaction is carried out at room temperature for 10-24 hours to obtain a white precipitate, which is the final product.
6. The preparation method according to claim 5, characterized in that, The organic solvent is one or a mixture of two of anhydrous acetone and anhydrous tetrahydrofuran, preferably anhydrous acetone; the molar ratio of β-propiolactone to N-(3-dimethylaminopropyl)acrylamide is 1.5:1 to 1:1, preferably 1.2:1 to 1:
1.
7. The preparation method according to claim 1, characterized in that, The preparation of the acrylate carboxybetaine (ACBMA) includes the following steps: 1) under the protection of an inert gas and with the action of a catalyst and a polymerization inhibitor, 2-hydroxyethyl acrylate is reacted with 1,6-hexanediisocyanate to obtain a semi-encapsulated compound containing acrylate isocyanate. 2) Under ice bath and inert gas protection, the semi-encapsulated isocyanate compound containing acrylate obtained in step 1) is subjected to nucleophilic addition reaction with N,N-dimethylethylenediamine to obtain an acrylate monomer containing carbamate and urea groups; 3) Under inert gas protection, the acrylate monomer containing carbamate and urea groups obtained in step 2) is reacted with β-propiolactone to obtain the zwitterionic monomer ACBMA.
8. The preparation method according to claim 7, characterized in that, The catalyst mentioned in step 1) is dibutyltin dilaurate, and the molar ratio of 2-hydroxyethyl acrylate to 1,6-hexamethylene diisocyanate is 1.3:1 to 1:1, preferably 1.2:1 to 1:
1. The molar ratio of 2-hydroxyethyl acrylate to the catalyst is 1:0.01 to 1:0.05, preferably 1:0.01 to 1:0.
03. The polymerization inhibitor is hydroquinone or p-methoxyphenol, preferably p-methoxyphenol, and the molar ratio of 2-hydroxyethyl acrylate to the polymerization inhibitor is 1:0.01 to 1:0.05, preferably 1:0.01 to 1:0.
03.
9. The preparation method according to claim 7, characterized in that, In step 2), the molar ratio of the semi-encapsulated isocyanate compound containing acrylate to N,N-dimethylethylenediamine is 0.7:1 to 1:1, preferably 0.8:1 to 1:1; in step 3), the reaction solvent is anhydrous chloroform or anhydrous dichloromethane, preferably anhydrous dichloromethane; the molar ratio of β-propiolactone to acrylate monomers containing carbamate and urea groups is 3:1 to 1:1, preferably 2:1 to 1:
1.
10. A corneal contact lens with self-healing function prepared by the preparation method according to any one of claims 1-9.