Carboxylated chitosan modified silicone hydrogel contact lens material and preparation method thereof

Abstract

The invention belongs to the technical field of hydrogel materials, and discloses a carboxylated chitosan modified silicone hydrogel contact lens material and a preparation method thereof. The preparation method comprises the following steps: mixing a siloxane monomer, a zwitterionic monomer, a first cross-linking agent, an initiator and a first organic solvent, and carrying out polymerization reaction to obtain silicone hydrogel; and mixing the silicone hydrogel, carboxylated chitosan, a second cross-linking agent and a second organic solvent, and carrying out a cross-linking reaction to obtain the carboxylated chitosan modified silicone hydrogel contact lens material. The zwitterionic monomer is introduced into the siloxane monomer polymerization process, and the carboxylated chitosan is adopted to modify the silicone hydrogel, so that the protein adsorption resistance and antibacterial property of the contact lens material are effectively improved. Meanwhile, the raw materials are wide in source, the preparation method is simple and easy to operate, and large-scale industrial production can be achieved easily.

Description

Technical Field

[0001] The invention relates to the technical field of hydrogel materials, and in particular to a carboxylated chitosan modified silicone hydrogel contact lens material and a preparation method thereof. Background Art

[0002] With the widespread use of electronic devices, the number of myopic patients continues to grow. Contact lenses, as a vision correction tool designed based on the shape of the human cornea, are not only highly compatible with the physiological structure of the eye, but also have the functions of vision adjustment and beautification of appearance, and are deeply favored by consumers. At present, the basic materials of contact lenses on the market are mainly hydrogel materials. As we all know, hydrogel materials have a three-dimensional network structure composed of molecular cross-linking. It is a contact lens manufacturing substrate with excellent light transmittance, hydrophilicity and biocompatibility. Hydrophilic soft contact lenses made of hydroxyethyl methacrylate (HEMA) are the leading products in the current market.

[0003] Although contact lenses have brought many conveniences to daily life, their long-term wear carries the risk of visual fatigue and dry eyes, which are manifested as itchy and sore eyes, strong foreign body sensation, abnormal increase in secretions, unbearable dryness, and blurred vision. The root of the above problems is that ordinary contact lenses easily absorb proteins, lipids and collagen in tears, which are deposited on the surface of the lens, which not only provides living conditions for pathogens, but also may induce corneal edema. What is more troublesome is that due to long-term wear, the frequency and degree of friction between contact lenses and corneas increase, which may cause damage to the corneal epithelium and cause permanent vision damage. Therefore, the overall performance of existing contact lenses is poor and cannot meet the growing performance needs of patients. Summary of the invention

[0004] The purpose of the present invention is to provide a carboxylated chitosan modified silicone hydrogel contact lens material and a preparation method thereof, and to provide a contact lens material with excellent comprehensive performance.

[0005] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0006] The present invention provides a method for preparing a carboxylated chitosan modified silicone hydrogel contact lens material, comprising the following steps:

[0007] (1) mixing a siloxane monomer, a zwitterionic monomer, a first crosslinking agent, an initiator and a first organic solvent to perform a polymerization reaction to obtain a silicone hydrogel;

[0008] (2) mixing the silicone hydrogel, carboxylated chitosan, a second crosslinking agent and a second organic solvent described in step (1) to carry out a crosslinking reaction to obtain a carboxylated chitosan modified silicone hydrogel contact lens material;

[0009] The siloxane monomer in step (1) comprises one or more of bis-3-methacryloxypropylated tetramethyldisiloxane, methacryloxypropyltris(trimethylsiloxy)silane, (3-methacryloxy-2-hydroxypropoxy)propylbis(trimethylsiloxy)methyl and (3-methacryloxy-2-hydroxypropoxy)propylbis(trimethylsiloxy)methylsilane;

[0010] The zwitterionic monomers in step (1) include carboxybetaine monomers and / or sulfobetaine monomers.

[0011] Preferably, in the preparation method, in step (1), the first cross-linking agent includes one or more of triethylene glycol dimethacrylate, ethylene glycol diacrylate, polyethylene glycol diacrylate, diethylene glycol diacrylate and tripropylene glycol diacrylate, the initiator includes one or more of azobisisoheptylnitrile, azobisisobutyronitrile and benzoyl peroxide, and the first organic solvent includes one or more of n-butanol, n-hexanol and isopropanol.

[0012] Preferably, in the preparation method, the carboxybetaine monomers include one or more of carboxybetaine acrylamide, carboxybetaine methacrylamide and carboxybetaine methacrylate, and the sulfonate monomers include one or more of sulfonate acrylamide, sulfonate methacrylamide and sulfonate methacrylate.

[0013] Preferably, in the preparation method, in step (1), the mass ratio of the siloxane monomer, the zwitterionic monomer, the first cross-linking agent and the initiator is 1:0.5-1.8:0.1-0.4:0.1-0.4.

[0014] Preferably, in the preparation method, in step (1), the polymerization reaction temperature is 50 to 80° C. and the reaction time is 8 to 15 hours.

[0015] Preferably, in the preparation method, in step (2), the preparation method of the carboxylated chitosan comprises the following steps:

[0016] (1) Under acidic conditions, chitosan, α-ketoglutaric acid and sodium borohydride are reacted to obtain N-ketoglutaric acid-chitosan;

[0017] (2) Under alkaline conditions, N-ketoglutaric acid-chitosan is reacted with chloroacetic acid to obtain carboxylated chitosan.

[0018] Preferably, in the preparation method, in step (2), the second cross-linking agent includes toluene diisocyanate or isophorone diisocyanate, and the second organic solvent is N,N-dimethylformamide.

[0019] Preferably, in the preparation method, in step (2), the mass ratio of the silicone hydrogel, the carboxylated chitosan and the second cross-linking agent is 1:0.4-1.2:0.05-0.2.

[0020] Preferably, in the preparation method, in step (2), the temperature of the cross-linking reaction is 90 to 120° C., and the time is 5 to 10 hours.

[0021] The invention also provides a carboxylated chitosan modified silicone hydrogel contact lens material prepared by the preparation method.

[0022] It can be seen from the above technical solution that compared with the prior art, the present invention has the following beneficial effects:

[0023] (1) The preparation method of the present invention selects siloxane monomer as the basic raw material of the hydrogel, which can ensure that the contact lens material has higher oxygen permeability. This is because the Si-Si bond and Si-O bond in the siloxane monomer structure can spontaneously construct an optimized gas conduction path, allowing oxygen to penetrate the material smoothly and unimpeded, meeting the cornea's demand for oxygen, avoiding dry eyes and fatigue caused by hypoxia to a certain extent, and improving wearing comfort to a certain extent.

[0024] (2) The present invention introduces zwitterionic monomers into the polymerization process of siloxane monomers. Zwitterionic monomers have positive and negative charge groups, which are evenly distributed to maintain charge balance at the molecular level, so that the surface of the silicone hydrogel obtained by polymerization is not easy to generate local charges, avoiding protein adsorption caused by charge attraction; at the same time, the introduction of zwitterionic monomers can produce a strong hydration effect through ion solvation, so that a tight layer of water molecules is formed on the surface of the silicone hydrogel as a barrier, directly hindering the direct contact between proteins, bacteria and other substances and the surface of the silicone hydrogel, thereby effectively reducing the adhesion of pollutants. In addition, zwitterionic monomers have excellent hydrophilicity and water retention, and are a raw material with good biocompatibility, which is conducive to improving the water content of silicone hydrogels.

[0025] (3) The present invention uses carboxylated chitosan to modify the silicone hydrogel. Since chitosan has certain antibacterial properties, it can prevent bacterial growth to a certain extent. Even if bacteria are produced in the contact lens material due to improper operation of myopic patients, since the amino and hydroxyl groups on the chitosan are carboxylated, the chitosan is electronegative as a whole, with the same charge as bacteria and most proteins, and the adhesion of silicone hydrogel to proteins and bacteria can be further reduced through charge repulsion. In addition, carboxylated chitosan also has excellent hydrophilicity, which is beneficial to improve the wettability of contact lens materials. At the same time, since carboxylated chitosan has excellent biocompatibility, it can effectively fit with the human cornea and is non-irritating to the human body.

[0026] (4) The raw materials of the present invention are widely available, and the preparation method is simple and easy to operate, which reduces the production cost and is conducive to large-scale industrial production. DETAILED DESCRIPTION

[0027] The present invention provides a method for preparing a carboxylated chitosan modified silicone hydrogel contact lens material, comprising the following steps:

[0028] (1) mixing a siloxane monomer, a zwitterionic monomer, a first crosslinking agent, an initiator and a first organic solvent to perform a polymerization reaction to obtain a silicone hydrogel;

[0029] (2) mixing the silicone hydrogel, carboxylated chitosan, a second crosslinking agent and a second organic solvent described in step (1) to carry out a crosslinking reaction to obtain a carboxylated chitosan modified silicone hydrogel contact lens material;

[0030] The siloxane monomer in step (1) comprises one or more of bis-3-methacryloxypropylated tetramethyldisiloxane, methacryloxypropyltris(trimethylsiloxy)silane, (3-methacryloxy-2-hydroxypropoxy)propylbis(trimethylsiloxy)methyl and (3-methacryloxy-2-hydroxypropoxy)propylbis(trimethylsiloxy)methylsilane;

[0031] The zwitterionic monomers in step (1) include carboxybetaine monomers and / or sulfobetaine monomers.

[0032] In the present invention, the method of mixing the siloxane monomer, the zwitterionic monomer, the first crosslinking agent, the initiator and the first organic solvent in step (1) is preferably as follows: the siloxane monomer and the first organic solvent are uniformly mixed, the zwitterionic monomer is added thereto and mixed uniformly, after heating to the temperature required for the polymerization reaction, the first crosslinking agent and the initiator are added thereto to react.

[0033] In the present invention, the siloxane monomer in step (1) preferably includes bis-3-methacryloxypropylated tetramethyldisiloxane, methacryloxypropyl tris(trimethylsiloxy)silane, (3-methacryloxy-2-hydroxypropoxy)propyl bis(trimethylsiloxy)methyl or (3-methacryloxy-2-hydroxypropoxy)propyl bis(trimethylsiloxy)methyl silane, further preferably bis-3-methacryloxypropylated tetramethyldisiloxane, methacryloxypropyl tris(trimethylsiloxy)silane or (3-methacryloxy-2-hydroxypropoxy)propyl bis(trimethylsiloxy)methyl, and more preferably methacryloxypropyl tris(trimethylsiloxy)silane.

[0034] In the present invention, the zwitterionic monomer in step (1) preferably includes a carboxybetaine monomer or a sulfobetaine monomer, and more preferably includes a sulfobetaine monomer.

[0035] In the present invention, the carboxybetaine monomer preferably includes one or more of carboxybetaine acrylamide, carboxybetaine methacrylamide and carboxybetaine methacrylate, and further preferably includes carboxybetaine acrylamide, carboxybetaine methacrylamide or carboxybetaine methacrylate, and more preferably is carboxybetaine methacrylate.

[0036] In the present invention, the sulfobetaine monomer preferably includes one or more of sulfobetaine acrylamide, sulfobetaine methacrylamide and sulfobetaine methacrylate, further preferably includes sulfobetaine acrylamide, sulfobetaine methacrylamide or sulfobetaine methacrylate, and more preferably is sulfobetaine methacrylate.

[0037] In the present invention, the first cross-linking agent in step (1) preferably includes one or more of triethylene glycol dimethacrylate, ethylene glycol diacrylate, polyethylene glycol diacrylate, diethylene glycol diacrylate and tripropylene glycol diacrylate, and further preferably includes triethylene glycol dimethacrylate, ethylene glycol diacrylate, polyethylene glycol diacrylate, diethylene glycol diacrylate or tripropylene glycol diacrylate, and more preferably is ethylene glycol diacrylate.

[0038] In the present invention, the initiator in step (1) preferably includes one or more of azobisisoheptanonitrile, azobisisobutyronitrile and benzoyl peroxide, and further preferably includes azobisisoheptanonitrile, azobisisobutyronitrile or benzoyl peroxide, and more preferably is benzoyl peroxide.

[0039] In the present invention, the first organic solvent in step (1) preferably includes one or more of n-butanol, n-hexanol and isopropanol, further preferably includes n-butanol, n-hexanol or isopropanol, and more preferably isopropanol.

[0040] In the present invention, when the siloxane monomer, the zwitterionic monomer, the first crosslinking agent, the initiator and the first organic solvent in step (1) are independently preferably multiple types, the ratio between the types is not limited and can be adjusted according to needs.

[0041] In the present invention, the mass ratio of the siloxane monomer, the zwitterionic monomer, the first crosslinking agent and the initiator in step (1) is preferably 1:0.5-1.8:0.1-0.4:0.1-0.4, more preferably 1:0.6-1.6:0.2-0.35:0.2-0.35, and more preferably 1:1.2:0.3:0.3.

[0042] In the present invention, the mass-to-volume ratio of the siloxane monomer to the first organic solvent in step (1) is preferably 1 g: 20-60 mL, more preferably 1 g: 25-50 mL, and even more preferably 1 g: 35 mL.

[0043] In the present invention, the polymerization reaction temperature in step (1) is preferably 50-80°C, more preferably 55-75°C, and more preferably 75°C; the polymerization reaction time is preferably 8-15h, more preferably 10-15h, and more preferably 12h.

[0044] In the present invention, after the polymerization reaction in step (1), the process preferably further comprises: soaking and cleaning the product using alcohol or water respectively.

[0045] In the present invention, the number of alcohol immersion cleaning is preferably 1 to 2 times, more preferably 2 times; the number of water immersion cleaning is preferably 3 to 6 times, more preferably 4 to 6 times, and more preferably 5 times.

[0046] In the present invention, the method of mixing the silicone hydrogel, carboxylated chitosan, the second crosslinking agent and the second organic solvent in step (2) is preferably as follows: after the carboxylated chitosan, the second organic solvent and the second crosslinking agent are uniformly mixed, the silicone hydrogel is added thereto and mixed uniformly.

[0047] In the present invention, the method for preparing the carboxylated chitosan in step (2) preferably comprises the following steps:

[0048] (1) Under acidic conditions, chitosan, α-ketoglutaric acid and sodium borohydride are reacted to obtain N-ketoglutaric acid-chitosan;

[0049] (2) Under alkaline conditions, N-ketoglutaric acid-chitosan is reacted with chloroacetic acid to obtain carboxylated chitosan.

[0050] In the method for preparing carboxylated chitosan of the present invention, the relative molecular weight of the chitosan in step (1) is preferably 4000-20000, more preferably 8000-12000, and more preferably 10000; the degree of deacetylation is preferably 85-95%, more preferably 88-92%, and more preferably 90%.

[0051] In the present invention, other parameter conditions in the method for preparing the carboxylated chitosan are not limited, and schemes well known to those skilled in the art can be adopted.

[0052] In the present invention, the second cross-linking agent in step (2) preferably includes toluene diisocyanate or isophorone diisocyanate, and more preferably toluene diisocyanate.

[0053] In the present invention, the second organic solvent in step (2) is preferably N,N-dimethylformamide.

[0054] In the present invention, the mass ratio of the silicone hydrogel, the carboxylated chitosan and the second cross-linking agent in step (2) is preferably 1:0.4-1.2:0.05-0.2, more preferably 1:0.5-1:0.08-0.15, and more preferably 1:1:0.1.

[0055] In the present invention, the mass-to-volume ratio of the silicone hydrogel to the second organic solvent in step (2) is preferably 1 g: 20-50 mL, more preferably 1 g: 25-40 mL, and even more preferably 1 g: 35 mL.

[0056] In the present invention, the temperature of the cross-linking reaction in step (2) is preferably 90-120°C, more preferably 100-120°C, and more preferably 120°C; the time is preferably 5-10h, more preferably 6-8h, and more preferably 8h.

[0057] In the present invention, after the cross-linking reaction in step (2), the process preferably further comprises: washing the product with ethanol and then soaking it with water.

[0058] In the present invention, the number of times of washing with ethanol is preferably 1 to 3 times, more preferably 2 to 3 times, and even more preferably 3 times.

[0059] In the present invention, the soaking time in water is preferably 12 to 36 hours, more preferably 18 to 30 hours, and even more preferably 24 hours.

[0060] The invention also provides a carboxylated chitosan modified silicone hydrogel contact lens material prepared by the preparation method.

[0061] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0062] Preparation Example 1

[0063] This preparation example provides a method for preparing carboxylated chitosan, comprising the following steps:

[0064] (1) 2 g of chitosan (relative molecular weight of 10,000, degree of deacetylation of 90%) was dissolved in 60 mL of 1 wt% acetic acid aqueous solution, 3.2 g of α-ketoglutaric acid was added, and the mixture was stirred at 37° C. for 24 h. Then, 0.8 g of sodium borohydride was added to the solution, and the reaction was continued at 37° C. for 10 h. The reaction was terminated with 95% ethanol to obtain a fibrous solid, which was filtered, washed three times with ethanol and ether respectively, and dried naturally to obtain N-ketoglutaric acid-chitosan;

[0065] (2) 1 g of N-ketoglutaric acid-chitosan obtained in step (1) and 1.36 g of sodium hydroxide were added to 40 mL of distilled water, and the mixture was stirred at 60° C. for alkalization and swelling for 1 h. Then, 10 mL of an aqueous solution containing 0.10 g of chloroacetic acid was added, and the reaction was continued at 60° C. for 10 h. After precipitating with acetone, the mixture was filtered, and the solid was washed with 95 wt % ethanol and dried to obtain a white powder of carboxylated chitosan.

[0066] Example 1

[0067] This embodiment provides a method for preparing a carboxylated chitosan modified silicone hydrogel contact lens material, comprising the following steps:

[0068] (1) Methacryloyloxypropyl tris(trimethylsiloxy)silane and isopropanol are mixed evenly, the mass to volume ratio of methacryloyloxypropyl tris(trimethylsiloxy)silane to isopropanol is 1g:35mL, sulfobetaine methacrylate is added thereto and mixed evenly, after heating to 75°C, ethylene glycol diacrylate and benzoyl peroxide are added thereto, the mass ratio of methacryloyloxypropyl tris(trimethylsiloxy)silane, sulfobetaine methacrylate, ethylene glycol diacrylate and benzoyl peroxide is 1:1.2:0.3:0.3, and the reaction is carried out for 12 hours; after the reaction is completed, the product is respectively washed with alcohol immersion for 2 times and water immersion for 5 times to obtain a silicone hydrogel;

[0069] (2) After the carboxylated chitosan, N,N-dimethylformamide and toluene diisocyanate obtained in Preparation Example 1 are mixed evenly, the silicone hydrogel obtained in step (1) is added thereto and mixed evenly, wherein the mass ratio of silicone hydrogel, carboxylated chitosan and toluene diisocyanate is 1:1:0.1, and the mass to volume ratio of silicone hydrogel and N,N-dimethylformamide is 1 g:35 mL. The cross-linking reaction is carried out at 120° C. for 8 h. After the reaction is completed, the product is washed with ethanol for 3 times and then soaked in water for 24 h to obtain a carboxylated chitosan modified silicone hydrogel contact lens material.

[0070] Example 2

[0071] This embodiment provides a method for preparing a carboxylated chitosan modified silicone hydrogel contact lens material, comprising the following steps:

[0072] (1) (3-methacryloyloxy-2-hydroxypropoxy)propyl bis(trimethylsiloxy)methyl and n-hexanol are mixed evenly, the mass to volume ratio of (3-methacryloyloxy-2-hydroxypropoxy)propyl bis(trimethylsiloxy)methyl and n-hexanol is 1g:50mL, carboxy betaine methacrylate is added thereto and mixed evenly, after heating to 60°C, diethylene glycol diacrylate and azobisisobutyronitrile are added thereto, the mass ratio of (3-methacryloyloxy-2-hydroxypropoxy)propyl bis(trimethylsiloxy)methyl, carboxy betaine methacrylate, diethylene glycol diacrylate and azobisisobutyronitrile is 1:0.6:0.2:0.2, and the reaction is carried out for 10 hours; after the reaction is completed, the product is respectively washed once with alcohol and washed 6 times with water to obtain a silicone hydrogel;

[0073] (2) After the carboxylated chitosan, N,N-dimethylformamide and isophorone diisocyanate obtained in Preparation Example 1 are mixed evenly, the silicone hydrogel obtained in step (1) is added thereto and mixed evenly, wherein the mass ratio of silicone hydrogel, carboxylated chitosan and isophorone diisocyanate is 1:1.2:0.08, and the mass to volume ratio of silicone hydrogel and N,N-dimethylformamide is 1 g:40 mL. The cross-linking reaction is carried out at 100° C. for 10 hours. After the reaction is completed, the product is washed twice with ethanol and then soaked in water for 24 hours to obtain a carboxylated chitosan modified silicone hydrogel contact lens material.

[0074] Example 3

[0075] This embodiment provides a method for preparing a carboxylated chitosan modified silicone hydrogel contact lens material, comprising the following steps:

[0076] (1) Bis-3-methacryloxypropylated tetramethyldisiloxane and isopropanol are mixed evenly, the mass to volume ratio of bis-3-methacryloxypropylated tetramethyldisiloxane to isopropanol is 1 g: 25 mL, sulfobetaine methacrylamide is added thereto and mixed evenly, after heating to 55° C., tripropylene glycol diacrylate and azobisisoheptanenitrile are added thereto, the mass ratio of bis-3-methacryloxypropylated tetramethyldisiloxane, sulfobetaine methacrylamide, tripropylene glycol diacrylate and azobisisoheptanenitrile is 1: 1.6: 0.35: 0.35, and the reaction is carried out for 15 hours; after the reaction is completed, the product is respectively washed with alcohol immersion for 2 times and water immersion for 4 times to obtain a silicone hydrogel;

[0077] (2) After the carboxylated chitosan, N,N-dimethylformamide and toluene diisocyanate obtained in Preparation Example 1 are mixed evenly, the silicone hydrogel obtained in step (1) is added thereto and mixed evenly, wherein the mass ratio of silicone hydrogel, carboxylated chitosan and toluene diisocyanate is 1:0.5:0.2, and the mass to volume ratio of silicone hydrogel and N,N-dimethylformamide is 1 g:25 mL. The cross-linking reaction is carried out at 110° C. for 6 hours. After the reaction is completed, the product is washed with ethanol for 3 times and then soaked in water for 24 hours to obtain a carboxylated chitosan modified silicone hydrogel contact lens material.

[0078] Comparative Example 1

[0079] This comparative example provides a method for preparing a carboxylated chitosan modified silicone hydrogel contact lens material, which differs from Example 1 in that sulfobetaine methacrylate in step (1) of Example 1 is deleted, and other parameter conditions are the same as those of Example 1.

[0080] Comparative Example 2

[0081] This comparative example provides a method for preparing a silicone hydrogel contact lens material, which differs from Example 1 in that the carboxylated chitosan in step (2) of Example 1 is deleted, and other parameter conditions are the same as those of Example 1.

[0082] Comparative Example 3

[0083] This comparative example provides a method for preparing a chitosan-modified silicone hydrogel contact lens material. The difference from Example 1 is that the carboxylated chitosan in step (2) of Example 1 is replaced by chitosan (relative molecular weight of 10,000, degree of deacetylation of 90%), and the other parameter conditions are the same as those in Example 1.

[0084] Test Example 1

[0085] The light transmittance of the materials obtained in Examples 1 to 3 and Comparative Examples 1 to 3 was tested according to GB / T 11417.5-2012 “Ophthalmic Optics Contact Lenses Part 5: Test Methods for Optical Properties”. The results are shown in Table 1.

[0086] Table 1. Transmittance test results

[0087] Case Example 1 Example 2 Example 3 Comparative Example 1 Comparative Example 2 Comparative Example 3 Light transmittance (%) 92.5 94.4 90.8 95.6 93.2 94.1

[0088] As can be seen from Table 1, although the transmittance of the carboxylated chitosan modified silicone hydrogel contact lens materials obtained in Examples 1 to 3 is slightly lower than that of Comparative Example 1 without adding zwitterionic monomers, it can be maintained above 90%, indicating that the scheme of adding zwitterionic monomers to silicone hydrogels for copolymerization and modifying the silicone hydrogels with carboxylated chitosan will not greatly reduce the transmittance of the materials, and the materials prepared by the present invention can meet the daily use requirements of contact lenses.

[0089] Test Example 2

[0090] The moisture content of the materials obtained in Examples 1 to 3 and Comparative Examples 1 to 3 was tested according to GB / T 11417.7-2012 “Ophthalmic Optics Contact Lenses Part 7: Test Methods for Physical and Chemical Properties”. The results are shown in Table 2.

[0091] Table 2. Moisture content test results

[0092] Case Example 1 Example 2 Example 3 Comparative Example 1 Comparative Example 2 Comparative Example 3 Moisture content (%) 58.2 56.7 59.3 53.9 56.1 57.6

[0093] As can be seen from Table 2, the water content of the carboxylated chitosan modified silicone hydrogel contact lens materials obtained in Examples 1 to 3 is higher than that of Comparative Example 1 without adding zwitterionic monomers, and is equivalent to or even slightly higher than that of Comparative Examples 2 to 3, indicating that both zwitterionic monomers and carboxylated chitosan are hydrophilic materials and will not reduce the water content of silicone hydrogel.

[0094] Test Example 3

[0095] The oxygen permeability coefficients of the materials obtained in Examples 1 to 3 and Comparative Examples 1 to 3 were tested according to GB / T 11417.7-2012 “Ophthalmic Optics Contact Lenses Part 7: Test Methods for Physical and Chemical Properties”. The results are shown in Table 3.

[0096] Table 3. Oxygen permeability test results

[0097]

[0098] As can be seen from Table 3, the oxygen permeability of the carboxylated chitosan modified silicone hydrogel contact lens materials obtained in Examples 1 to 3 is slightly lower than that of Comparative Example 2 without adding carboxylated chitosan, but can be maintained at 85% or above. For Comparative Examples 1 and 3, the addition of carboxylated chitosan or chitosan will slightly reduce the oxygen permeability coefficient, indicating that the amount of carboxylated chitosan needs to be controlled within a reasonable range.

[0099] Test Example 4

[0100] The anti-protein adsorption properties of the materials obtained in Examples 1 to 3 and Comparative Examples 1 to 3 were tested. The testing method was as follows: a circular gel sheet with a diameter of 10 mm and a height of 3 mm was soaked in 10 mL of PBS solution for 30 min, then transferred to 10 mL of 1.0 mg / mL bovine serum albumin (BSA) solution and soaked for 24 h, 1 mL of the soaked BSA solution was taken, 5 mL of 0.1 mg / mL Coomassie Brilliant Blue solution was added, and dyed for 5 min, the ultraviolet absorbance of the solution was measured at 595 nm, and the corresponding concentration of the BSA solution after adsorption was calculated according to the standard curve; and the relative adsorption amount of the protein was calculated according to Formula 1, and the results are shown in Table 4.

[0101]

[0102] In formula 1, q is the relative adsorption amount of protein; C 前 is the initial concentration of BSA; C 后 is the BSA concentration after adsorption.

[0103] Table 4. Anti-protein adsorption test results

[0104]

[0105] As shown in Table 4, the protein adsorption amount of the carboxylated chitosan modified silicone hydrogel contact lens material obtained in Examples 1 to 3 decreases with the increase in the relative amount of zwitterionic monomer and carboxylated chitosan. Since no zwitterionic monomer is added in Comparative Example 1 and no carboxylated chitosan is added in Comparative Example 2, the protein adsorption amount is greatly increased, indicating that the material's anti-protein adsorption performance is correlated with both zwitterionic monomer and carboxylated chitosan, and the two have a synergistic effect. For Comparative Example 3, although chitosan is added, since chitosan is not carboxylated, its anti-protein adsorption is far inferior to that of Examples 1 to 3, indicating that the carboxylation modification of chitosan will also reduce the adhesion of silicone hydrogel to protein.

[0106] Test Example 5

[0107] The antibacterial properties of the materials obtained in Examples 1 to 3 and Comparative Examples 1 to 3 were tested as follows: a cotton swab was dipped in a 10% 6CFU / mL of Staphylococcus aureus liquid was evenly spread on MH agar medium. After the liquid was completely absorbed by the agar, contact lens materials with a diameter of 10 mm were attached to the agar medium and cultured at 37°C for 24 h. A cotton swab was used to dip a 10 6 coli liquid with a concentration of 0.1 CFU / mL was evenly spread on NZYM broth medium. After the liquid was completely absorbed by agar, contact lens materials with a diameter of 10 mm were attached to the agar medium and cultured at 37°C for 24 h. The antibacterial ring diameter of the two test schemes was measured (antibacterial ring diameter = antibacterial ring outer diameter - measured sample diameter). The results are shown in Table 5.

[0108] Table 5. Antibacterial test results

[0109]

[0110] As shown in Table 5, the antibacterial properties of the carboxylated chitosan-modified silicone hydrogel contact lens materials obtained in Examples 1 to 3 are better than those in Comparative Examples 1 to 3. Specifically, Comparative Example 1 has antibacterial properties due to the addition of carboxylated chitosan; although Comparative Example 2 does not add carboxylated chitosan, the antibacterial properties are seriously reduced, but since the zwitterionic monomers therein inhibit the adsorption of proteins to a certain extent and reduce the nutrient source for bacterial growth, it still has a relatively low antibacterial property; Comparative Example 3 does not show a significant decrease in antibacterial properties due to the addition of chitosan, but since chitosan is not carboxylated, the ability to resist protein adsorption is reduced, and therefore it cannot better block the nutrient source of bacteria, and the antibacterial properties are reduced.

[0111] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A method for preparing a carboxylated chitosan modified silicone hydrogel contact lens material, characterized in that: The following steps are involved: (1) mixing a siloxane monomer, a zwitterionic monomer, a first crosslinking agent, an initiator and a first organic solvent to perform a polymerization reaction to obtain a silicone hydrogel; (2) mixing the silicone hydrogel, carboxylated chitosan, a second crosslinking agent and a second organic solvent described in step (1) to carry out a crosslinking reaction to obtain a carboxylated chitosan modified silicone hydrogel contact lens material; The siloxane monomer in step (1) comprises one or more of bis-3-methacryloxypropylated tetramethyldisiloxane, methacryloxypropyltris(trimethylsiloxy)silane, (3-methacryloxy-2-hydroxypropoxy)propylbis(trimethylsiloxy)methyl and (3-methacryloxy-2-hydroxypropoxy)propylbis(trimethylsiloxy)methylsilane; The zwitterionic monomers in step (1) include carboxybetaine monomers and / or sulfobetaine monomers.

2. The preparation method according to claim 1, characterized in that: In step (1), the first cross-linking agent includes one or more of triethylene glycol dimethacrylate, ethylene glycol diacrylate, polyethylene glycol diacrylate, diethylene glycol diacrylate and tripropylene glycol diacrylate, the initiator includes one or more of azobisisoheptylnitrile, azobisisobutyronitrile and benzoyl peroxide, and the first organic solvent includes one or more of n-butanol, n-hexanol and isopropanol.

3. The preparation method according to claim 1 or 2, characterized in that: The carboxybetaine monomers include one or more of carboxybetaine acrylamide, carboxybetaine methacrylamide and carboxybetaine methacrylate, and the sulfonobetaine monomers include one or more of sulfonobetaine acrylamide, sulfonobetaine methacrylamide and sulfonobetaine methacrylate.

4. The preparation method according to claim 3, characterized in that: In step (1), the mass ratio of the siloxane monomer, the zwitterionic monomer, the first crosslinking agent and the initiator is 1:0.5-1.8:0.1-0.4:0.1-0.

4.

5. The preparation method according to claim 1 or 4, characterized in that: In step (1), the polymerization reaction is carried out at a temperature of 50 to 80° C. and for a time of 8 to 15 hours.

6. The preparation method according to claim 1, characterized in that: In step (2), the preparation method of the carboxylated chitosan comprises the following steps: (1) Under acidic conditions, chitosan, α-ketoglutaric acid and sodium borohydride are reacted to obtain N-ketoglutaric acid-chitosan; (2) Under alkaline conditions, N-ketoglutaric acid-chitosan is reacted with chloroacetic acid to obtain carboxylated chitosan.

7. The preparation method according to claim 1 or 6, characterized in that: In step (2), the second cross-linking agent includes toluene diisocyanate or isophorone diisocyanate, and the second organic solvent is N,N-dimethylformamide.

8. The preparation method according to claim 7, characterized in that: In step (2), the mass ratio of the silicone hydrogel, the carboxylated chitosan and the second cross-linking agent is 1:0.4-1.2:0.05-0.

2.

9. The preparation method according to claim 1 or 8, characterized in that: In step (2), the temperature of the cross-linking reaction is 90 to 120° C., and the time is 5 to 10 hours.

10. The carboxylated chitosan modified silicone hydrogel contact lens material obtained by the preparation method according to any one of claims 1 to 9.

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