Moisturizing contact lens containing hyaluronic acid coating and preparation method thereof

Abstract

The invention belongs to the technical field of contact lenses, and provides a moisturizing contact lens containing a hyaluronic acid coating and a preparation method of the moisturizing contact lens. The preparation method comprises the following steps: carrying out ultrasonic mixing on a hydrophilic monomer, a siloxane monomer, a cross-linking agent and an initiator, injecting the mixed solution into a contact lens mold, and carrying out polymerization reaction to obtain a contact lens material; mixing the chitosan solution, the shellac acid solution, the hyaluronic acid solution and the vitamin E succinate solution to obtain a hyaluronic acid mixed solution; and soaking the contact lens material in the hyaluronic acid mixed solution, adding a cross-linking agent, curing, and drying to obtain the moisturizing contact lens containing the hyaluronic acid coating. The contact lens disclosed by the invention has excellent moisture retention, good light transmission performance, swelling performance and excellent mechanical property, the wearing comfort is remarkably improved, and the contact lens is suitable for being worn for a long time; the preparation method disclosed by the invention is environment-friendly and easy to industrialize.

Description

Technical Field

[0001] The present invention relates to the technical field of contact lenses, in particular to a moisturizing contact lens containing a hyaluronic acid coating and a preparation method thereof. Background Art

[0002] Contact lenses can be categorized by material as hard, soft, and gas-permeable. Soft contact lenses, particularly those made of hydrogel, are experiencing the most rapid growth. However, a significant challenge with hydrogel lenses is their poor oxygen permeability, with a typical wear time of only eight hours, far from meeting consumer expectations. To improve oxygen permeability, siloxane monomers have been copolymerized into hydrogel lenses. However, the hydrophobic nature of siloxane monomers results in poor water retention and self-wetting properties in the resulting lenses.

[0003] To address these issues, a hydrophilic layer can be formed on the surface of hydrogel contact lenses, such as by introducing hyaluronic acid into contact lenses as a hydrophilic layer. Hyaluronic acid is a glycosaminoglycan with strong water-retention and lubricity. It has the ability to form a highly hydrated and viscous matrix, imparting hardness, elasticity, and lubricity to various tissues. It is an effective space filler that maintains hydration, serves as a matrix for proteoglycan assembly and cell movement, regulates cell function and development, and participates in tumor progression, inflammation, and wound healing. Hyaluronic acid's unique lubricating effect makes it widely used in the treatment of dry eye, effectively alleviating dryness and eye fatigue.

[0004] Currently, contact lenses modified with hyaluronic acid still face challenges such as complex manufacturing processes, difficult preparation procedures, and substandard water content and moisture retention. Therefore, developing a moisturizing contact lens with a hyaluronic acid coating that improves water content, moisture retention, and wearing comfort is of great significance. Summary of the Invention

[0005] The purpose of the present invention is to provide a moisturizing contact lens containing a hyaluronic acid coating and a preparation method thereof in view of the deficiencies in the prior art.

[0006] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0007] The present invention provides a method for preparing a moisturizing contact lens containing a hyaluronic acid coating, comprising the following steps:

[0008] 1) ultrasonically mixing a hydrophilic monomer, a siloxane monomer, a crosslinking agent, and an initiator, injecting the mixed solution into a contact lens mold, performing a polymerization reaction, and then drying to obtain a contact lens material;

[0009] 2) mixing the chitosan solution, the shellacic acid solution, the hyaluronic acid solution, and the vitamin E succinate solution to obtain a hyaluronic acid mixture;

[0010] 3) Soaking the contact lens material in the hyaluronic acid mixed solution, adding a cross-linking agent for curing and then drying to obtain a moisturizing contact lens containing a hyaluronic acid coating.

[0011] Preferably, in step 1), the hydrophilic monomer comprises hydroxyethyl methacrylate and / or 2-methacryloyloxyethyl phosphorylcholine; and the siloxane monomer comprises vinyl polydimethylsiloxane and / or γ-methacryloyloxypropyltrimethoxysilane.

[0012] Preferably, in step 1), the crosslinking agent is ethylene glycol dimethacrylate and / or triethylene glycol dimethacrylate; the initiator is a photoinitiator or a thermal initiator, the thermal initiator comprises azobisisobutyronitrile, azobisisoheptanenitrile or dibenzoyl peroxide; the photoinitiator comprises 2-hydroxy-2-methyl-1-phenylpropanone, 1-hydroxy-cyclohexylphenyl ketone, 4-phenylbenzophenone or methyl o-benzoylbenzoate.

[0013] Preferably, in step 1), the mass of the cross-linking agent is 1-2% of the total mass of the hydrophilic monomer and the siloxane monomer, the mass of the initiator is 1-2% of the total mass of the hydrophilic monomer and the siloxane monomer, and the molar ratio of the hydrophilic monomer to the siloxane monomer is 30-40:1-3.

[0014] Preferably, the polymerization reaction in step 1) is a thermal polymerization reaction or a photopolymerization reaction. The temperature of the thermal polymerization reaction is 70 to 90° C. and the time is 8 to 10 hours. The time of the photopolymerization reaction is 3 to 10 minutes.

[0015] Preferably, in step 2), the mass concentration of the chitosan solution is 5-10%, the mass concentration of the shellacic acid solution is 4-7%, the mass concentration of the hyaluronic acid solution is 4-6%, and the mass concentration of the vitamin E succinate solution is 3-5%;

[0016] The volume ratio of the chitosan solution, the shellacic acid solution, the hyaluronic acid solution and the vitamin E succinate solution is 1-2:0.8-1:1:0.3-0.5.

[0017] Preferably, in step 3), the mass ratio of the cross-linking agent to the hyaluronic acid mixture is 0.8-1.5:100; and the cross-linking agent is genipin.

[0018] Preferably, the curing temperature in step 3) is 30-40° C. and the curing time is 10-20 minutes.

[0019] The present invention also provides a moisturizing contact lens containing a hyaluronic acid coating prepared by the preparation method.

[0020] The beneficial effects of the present invention include the following:

[0021] 1) The hyaluronic acid of the present invention can improve the lubricity of contact lenses, relieve eye fatigue, and greatly improve the wearing comfort of contact lenses, especially the comfort of long-term wear; vitamin E succinate has the characteristics of good transparency, antioxidant and ultraviolet absorption; chitosan molecules contain hydroxyl groups, amino groups and the like, which interact with the carboxyl groups of shellacic acid to form a larger molecular structure, thereby increasing the loading capacity of hyaluronic acid and vitamin E succinate, allowing hyaluronic acid and vitamin E succinate to be present in the eyes for a long time, thereby avoiding problems such as dry eyes and bacterial infection caused by wearing contact lenses.

[0022] 2) The contact lenses of the present invention have excellent moisture retention, good light transmittance, swelling properties, and excellent mechanical properties, significantly improving wearing comfort and making them suitable for long-term wear. They can also load antibacterial drugs and extend the drug release time. The preparation method of the present invention is environmentally friendly and easy to industrialize. DETAILED DESCRIPTION

[0023] The present invention provides a method for preparing a moisturizing contact lens containing a hyaluronic acid coating, comprising the following steps:

[0024] 1) ultrasonically mixing a hydrophilic monomer, a siloxane monomer, a crosslinking agent, and an initiator, injecting the mixed solution into a contact lens mold, performing a polymerization reaction, and then drying to obtain a contact lens material;

[0025] 2) mixing the chitosan solution, the shellacic acid solution, the hyaluronic acid solution, and the vitamin E succinate solution to obtain a hyaluronic acid mixture;

[0026] 3) Soaking the contact lens material in the hyaluronic acid mixed solution, adding a cross-linking agent for curing and then drying to obtain a moisturizing contact lens containing a hyaluronic acid coating.

[0027] In the present invention, the hydrophilic monomer in step 1) preferably comprises hydroxyethyl methacrylate and / or 2-methacryloyloxyethyl phosphorylcholine; and the siloxane monomer preferably comprises vinyl polydimethylsiloxane and / or γ-methacryloyloxypropyltrimethoxysilane.

[0028] In the present invention, the cross-linking agent in step 1) is preferably ethylene glycol dimethacrylate (EGDMA) and / or triethylene glycol dimethacrylate (TEGDMA); the initiator is preferably a photoinitiator or a thermal initiator, and the thermal initiator preferably comprises azobisisobutyronitrile, azobisisoheptanenitrile or dibenzoyl peroxide; the photoinitiator preferably comprises 2-hydroxy-2-methyl-1-phenylpropanone (photoinitiator 1173), 1-hydroxy-cyclohexylphenyl ketone (photoinitiator 184), 4-phenylbenzophenone (photoinitiator PBZ) or methyl o-benzoylbenzoate (photoinitiator OMBB).

[0029] In the present invention, the mass of the cross-linking agent in step 1) is preferably 1 to 2% of the total mass of the hydrophilic monomer and the siloxane monomer, more preferably 1.2 to 1.8%, more preferably 1.5 to 1.6%, the mass of the initiator is preferably 1 to 2% of the total mass of the hydrophilic monomer and the siloxane monomer, more preferably 1.2 to 1.8%, more preferably 1.5 to 1.6%, the molar ratio of the hydrophilic monomer to the siloxane monomer is preferably 30 to 40:1 to 3, more preferably 32 to 38:1.5 to 2.5, more preferably 35 to 36:2.

[0030] In the present invention, the polymerization reaction in step 1) is preferably a thermal polymerization reaction or a photopolymerization reaction. The temperature of the thermal polymerization reaction is preferably 70 to 90°C, more preferably 75 to 85°C, and more preferably 80°C. The time of the thermal polymerization reaction is preferably 8 to 10 hours, more preferably 8.5 to 9.5 hours, and more preferably 9 hours. The time of the photopolymerization reaction is preferably 3 to 10 minutes, more preferably 5 to 8 minutes, and more preferably 6 to 7 minutes.

[0031] In the present invention, the mass concentration of the chitosan solution in step 2) is preferably 5-10%, more preferably 6-9%, and more preferably 7-8%. The mass concentration of the shellacic acid solution is preferably 4-7%, more preferably 5-6%. The mass concentration of the hyaluronic acid solution is preferably 4-6%, more preferably 4.5-5.5%, and more preferably 5%. The mass concentration of the vitamin E succinate solution is preferably 3-5%, more preferably 3.5-4.5%, and more preferably 4%.

[0032] The volume ratio of the chitosan solution, shellacic acid solution, hyaluronic acid solution and vitamin E succinate solution is preferably 1-2:0.8-1:1:0.3-0.5, more preferably 1.2-1.8:0.85-0.95:1:0.35-0.45, and even more preferably 1.4-1.5:0.9:1:0.4.

[0033] In the present invention, the solvent of the chitosan solution is acetic acid, the solvent of the shellacic acid solution and the vitamin E succinate solution is anhydrous ethanol, and the solvent of the hyaluronic acid solution is deionized water; the molecular weight of hyaluronic acid is preferably 800-1500 kDa, more preferably 1000-1200 kDa; the molecular weight of chitosan is preferably 20000-40000 Da, more preferably 25000-35000 Da.

[0034] In the present invention, the mass ratio of the cross-linking agent and the hyaluronic acid mixture in step 3) is preferably 0.8-1.5:100, more preferably 1-1.4:100, and even more preferably 1.2-1.3:100; the cross-linking agent is preferably genipin.

[0035] In the present invention, the curing temperature in step 3) is preferably 30-40°C, more preferably 32-38°C, more preferably 35-36°C, and the curing time is preferably 10-20 min, more preferably 12-18 min, more preferably 15-16 min.

[0036] The present invention also provides a moisturizing contact lens containing a hyaluronic acid coating prepared by the preparation method.

[0037] The technical solutions provided by the present invention are described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0038] In the embodiment, the chitosan solution is an acetic acid solution of chitosan, the shellac acid solution is an ethanol solution of shellac acid, the hyaluronic acid solution is an aqueous solution of hyaluronic acid, and the vitamin E succinate solution is an ethanol solution of vitamin E succinate; the molecular weight of chitosan is 25,000 to 35,000 Da, and the molecular weight of hyaluronic acid is 1,000 to 1,200 kDa.

[0039] Example 1

[0040] The hydrophilic monomer is hydroxyethyl methacrylate and 2-methacryloyloxyethyl phosphorylcholine in a molar ratio of 1:1, the siloxane monomer is vinyl polydimethylsiloxane, the crosslinker is ethylene glycol dimethacrylate, and the initiator is a thermal initiator azobisisobutyronitrile; the molar ratio of the hydrophilic monomer to the siloxane monomer is 35:2, the mass of the crosslinker is 1.5% of the total mass of the hydrophilic monomer and the siloxane monomer, and the mass of the initiator is 1.5% of the total mass of the hydrophilic monomer and the siloxane monomer.

[0041] The mass concentration of chitosan solution is 8%, the mass concentration of shellac acid solution is 6%, the mass concentration of hyaluronic acid solution is 5%, and the mass concentration of vitamin E succinate solution is 4%. The volume ratio of chitosan solution, shellac acid solution, hyaluronic acid solution and vitamin E succinate solution is 1.5:0.9:1:0.4; the mass ratio of the mixed solution of genipin and hyaluronic acid is 1.2:100.

[0042] The hydrophilic monomer, siloxane monomer, cross-linking agent and initiator are ultrasonically mixed at a frequency of 80 kHz for 10 minutes to obtain a uniform mixed solution, which is injected into a contact lens mold, subjected to a thermal polymerization reaction at 80°C for 9 hours, and then dried at room temperature. The mold is demolded to obtain a contact lens material; a chitosan solution, a shellac acid solution, a hyaluronic acid solution and a vitamin E succinate solution are mixed to obtain a hyaluronic acid mixed solution; the contact lens material is immersed in the hyaluronic acid mixed solution, genipin is added, and the mixture is cured at 35°C for 15 minutes and then dried at room temperature to obtain a moisturizing contact lens containing a hyaluronic acid coating.

[0043] Example 2

[0044] The hydrophilic monomer is hydroxyethyl methacrylate, the siloxane monomer is γ-methacryloxypropyltrimethoxysilane, the crosslinker is triethylene glycol dimethacrylate, and the initiator is photoinitiator 1173; the molar ratio of the hydrophilic monomer to the siloxane monomer is 30:1, the mass of the crosslinker is 1.2% of the total mass of the hydrophilic monomer and the siloxane monomer, and the mass of the initiator is 2% of the total mass of the hydrophilic monomer and the siloxane monomer.

[0045] The mass concentration of chitosan solution is 6%, the mass concentration of shellacic acid solution is 5%, the mass concentration of hyaluronic acid solution is 4%, and the mass concentration of vitamin E succinate solution is 3%. The volume ratio of chitosan solution, shellacic acid solution, hyaluronic acid solution and vitamin E succinate solution is 1.2:0.85:1:0.35; the mass ratio of the mixed solution of genipin and hyaluronic acid is 1:100.

[0046] The hydrophilic monomer, siloxane monomer, cross-linking agent and initiator are ultrasonically mixed at a frequency of 80 kHz for 10 minutes to obtain a uniform mixed solution, which is injected into a contact lens mold. The polymerization reaction is initiated by ultraviolet light for 8 hours, and then dried at room temperature. The mold is demolded to obtain a contact lens material; chitosan solution, shellac acid solution, hyaluronic acid solution and vitamin E succinate solution are mixed to obtain a hyaluronic acid mixed solution; the contact lens material is immersed in the hyaluronic acid mixed solution, genipin is added, and the mixture is cured at 30°C for 18 minutes and then dried at room temperature to obtain a moisturizing contact lens containing a hyaluronic acid coating.

[0047] Example 3

[0048] The hydrophilic monomer is 2-methacryloyloxyethyl phosphorylcholine, the siloxane monomer is vinyl polydimethylsiloxane, the crosslinker is ethylene glycol dimethacrylate, and the initiator is a thermal initiator dibenzoyl peroxide; the molar ratio of the hydrophilic monomer to the siloxane monomer is 40:3, the mass of the crosslinker is 1.8% of the total mass of the hydrophilic monomer and the siloxane monomer, and the mass of the initiator is 1.2% of the total mass of the hydrophilic monomer and the siloxane monomer.

[0049] The mass concentration of chitosan solution is 9%, the mass concentration of shellacic acid solution is 7%, the mass concentration of hyaluronic acid solution is 6%, the mass concentration of vitamin E succinate solution is 3.5%, the volume ratio of chitosan solution, shellacic acid solution, hyaluronic acid solution and vitamin E succinate solution is 1.8:0.95:1:0.45; the mass ratio of the mixed solution of genipin and hyaluronic acid is 1.3:100.

[0050] The hydrophilic monomer, siloxane monomer, cross-linking agent and initiator are ultrasonically mixed at a frequency of 80 kHz for 10 minutes to obtain a uniform mixed solution, which is injected into a contact lens mold, subjected to a thermal polymerization reaction at 75°C for 8.5 hours, and then dried at room temperature. The mold is demolded to obtain a contact lens material; a chitosan solution, a shellac acid solution, a hyaluronic acid solution and a vitamin E succinate solution are mixed to obtain a hyaluronic acid mixed solution; the contact lens material is immersed in the hyaluronic acid mixed solution, genipin is added, and the mixture is cured at 40°C for 12 minutes and then dried at room temperature to obtain a moisturizing contact lens containing a hyaluronic acid coating.

[0051] Comparative Example 1

[0052] The shellac acid solution and hyaluronic acid solution in Example 1 were omitted, and other conditions were the same as those in Example 1.

[0053] Comparative Example 2

[0054] The vitamin E succinate solution and siloxane monomer of Example 1 were omitted, and the volume ratio of the chitosan solution, the shellac acid solution, and the hyaluronic acid solution was 1:2:1.5. Other conditions were the same as those of Example 1.

[0055] The hydrophilicity, equilibrium water content, moisturizing rate and comfort of the contact lenses of Examples 1 to 3 and Comparative Examples 1 to 2 were tested.

[0056] The contact angles of the contact lenses were measured using a water contact angle tester (DSA-25). Each sample was tested three times in parallel and the average value was taken. The average contact angles of the contact lenses of Examples 1 to 3 were 38.40°, 36.85°, and 40.15°, respectively. The average contact angles of the contact lenses of Comparative Examples 1 and 2 were 72.55° and 68.15°, respectively.

[0057] After thoroughly soaking the contact lenses in distilled water, remove them, wipe off the surface moisture, and weigh them (wet weight). Then, dry them in a 60°C air drying oven until constant weight is reached. Remove them and weigh them (dry weight). The equilibrium moisture content is (wet weight - dry weight) / wet weight × 100%. The equilibrium moisture contents of the contact lenses of Examples 1-3 were 47%, 45%, and 48%, respectively, while the equilibrium moisture contents of the contact lenses of Comparative Examples 1-2 were 26% and 32%, respectively.

[0058] The moisturizing rates of the contact lenses of Examples 1 to 3 were 85%, 82%, and 78%, respectively. After wearing for 150 minutes, no dryness of the lenses, discomfort, or foreign body sensation occurred. They had excellent moisturizing performance and wearing comfort. The moisturizing rates of the contact lenses of Comparative Examples 1 to 2 were 57% and 51%, respectively. After wearing for 90 minutes, dryness of the lenses or foreign body sensation occurred.

[0059] The moisturizing contact lens containing the hyaluronic acid coating of the present invention has good hydrophilicity, excellent water content and moisture retention, good wearing comfort, and is suitable for long-term wear.

[0060] 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 principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. A method for preparing a moisturizing contact lens containing a hyaluronic acid coating, characterized in that: The following steps are included: 1) ultrasonically mixing a hydrophilic monomer, a siloxane monomer, a crosslinking agent, and an initiator, injecting the mixed solution into a contact lens mold, performing a polymerization reaction, and then drying to obtain a contact lens material; 2) mixing the chitosan solution, the shellacic acid solution, the hyaluronic acid solution, and the vitamin E succinate solution to obtain a hyaluronic acid mixture; 3) Soaking the contact lens material in the hyaluronic acid mixed solution, adding a cross-linking agent for curing and then drying to obtain a moisturizing contact lens containing a hyaluronic acid coating.

2. The preparation method according to claim 1, characterized in that In step 1), the hydrophilic monomer comprises hydroxyethyl methacrylate and / or 2-methacryloyloxyethyl phosphorylcholine; and the siloxane monomer comprises vinyl polydimethylsiloxane and / or γ-methacryloyloxypropyltrimethoxysilane.

3. The preparation method according to claim 1 or 2, characterized in that In step 1), the crosslinking agent is one or more of ethylene glycol dimethacrylate and / or triethylene glycol dimethacrylate and triethylene glycol dimethacrylate; the initiator is a photoinitiator or a thermal initiator, the thermal initiator comprises azobisisobutyronitrile, azobisisoheptanenitrile or dibenzoyl peroxide; the photoinitiator comprises 2-hydroxy-2-methyl-1-phenylpropanone, 1-hydroxy-cyclohexylphenyl ketone, 4-phenylbenzophenone or methyl o-benzoylbenzoate.

4. The preparation method according to claim 3, characterized in that In step 1), the mass of the crosslinking agent is 1-2% of the total mass of the hydrophilic monomer and the siloxane monomer, the mass of the initiator is 1-2% of the total mass of the hydrophilic monomer and the siloxane monomer, and the molar ratio of the hydrophilic monomer to the siloxane monomer is 30-40:1-3.

5. The preparation method according to claim 4, characterized in that The polymerization reaction in step 1) is a thermal polymerization reaction or a photopolymerization reaction. The temperature of the thermal polymerization reaction is 70-90° C. and the time is 8-10 hours. The time of the photopolymerization reaction is 3-10 minutes.

6. The preparation method according to claim 1 or 5, characterized in that Step 2) The mass concentration of the chitosan solution is 5-10%, the mass concentration of the shellacic acid solution is 4-7%, the mass concentration of the hyaluronic acid solution is 4-6%, and the mass concentration of the vitamin E succinate solution is 3-5%; The volume ratio of the chitosan solution, the shellacic acid solution, the hyaluronic acid solution and the vitamin E succinate solution is 1-2:0.8-1:1:0.3-0.

5.

7. The preparation method according to claim 6, characterized in that Step 3) The mass ratio of the cross-linking agent to the hyaluronic acid mixture is 0.8-1.5:100; the cross-linking agent is genipin.

8. The preparation method according to claim 7, characterized in that Step 3) The curing temperature is 30-40° C. and the curing time is 10-20 minutes.

9. A moisturizing contact lens containing a hyaluronic acid coating prepared by the preparation method according to any one of claims 1 to 8.