Functional silicone hydrogel contact lens implementing antibacterial and antioxidant properties through antibacterial peptide surface coating and manufacturing method therefor

Abstract

The present invention relates to a functional silicone hydrogel contact lens and a manufacturing method therefor, wherein the functional silicone hydrogel contact lens that achieves antibacterial and antioxidant properties through antibacterial peptide surface coating is manufactured by forming an antibacterial peptide coating layer on the contact lens surface, ensuring semi-permanent antibacterial and antioxidant effects. The contact lenses coated with dopamine and peptide of the present invention comprise: a contact lens formed from a hydroxyethyl methacrylate (HEMA) polymer; and a coating layer applied to the surface of the contact lens, formed using a coating solution in which polydopamine and an antibacterial peptide are mixed.

Description

Functional silicone hydrogel contact lenses with antibacterial and antioxidant properties through antibacterial peptide surface coating and method for manufacturing the same

[0001] The present invention relates to a functional silicone hydrogel contact lens having antibacterial and antioxidant properties through an antibacterial peptide surface coating, which forms an antibacterial peptide coating layer on the surface of the contact lens to manufacture a silicone hydrogel contact lens having semi-permanent antibacterial and antioxidant properties, and a method for manufacturing the same.

[0002] In general, contact lenses must meet the following requirements: adequate tensile strength, biocompatibility, non-toxicity, optical transparency, refractive index, surface wettability, corneal-compatible water content, swelling ratio, oxygen transmissibility, and flexibility.

[0003] In particular, considering the problems and side effects of ophthalmic diseases caused by long-term wear of contact lenses, the requirement of oxygen transmissibility is very important.

[0004] Therefore, research and development of materials with excellent oxygen permeability are actively being conducted to improve the oxygen permeability of contact lenses, and contact lenses made of silicone hydrogel are currently being manufactured in general.

[0005] Silicone hydrogel is a water-swellable network polymer with high oxygen permeability, and can be widely used as a monomer for manufacturing contact lenses, such as 3-[tris(trimethylsiloxy)silyl]propyl methacrylate.

[0006] Because typical silicone monomers are hydrophobic, the water content of hydrogel lenses manufactured using these monomers is low. Therefore, they are used in polymerization with hydrophilic monomers such as 2-hydroxyethyl methacrylate (HEMA) and are used as contact lens materials. However, because these hydrophobic silicone monomers do not mix with other hydrophilic monomers, the manufactured lenses are cloudy, have low light transmittance, and have poor water content.

[0007] Therefore, research on the development of novel silicone compounds is continuously required because oxygen permeability, light transmittance, and wettability can be simultaneously increased by manufacturing a hydrophilic silicone monomer and mixing it with HEMA, etc. to manufacture a hydrogel lens.

[0008] Meanwhile, contact lenses can cause infectious diseases such as bacterial keratitis due to improper care, and in severe cases, can lead to serious side effects such as corneal ulcers or blindness.

[0009] In particular, bacterial keratitis caused by bacterial infection is frequently caused by contact lenses that come into direct contact with the eye, so the need for the development of contact lenses with a fundamental antibacterial effect is rapidly increasing.

[0010] To address these issues, various methods are being explored both domestically and internationally to reduce bacterial biofilm formation in contact lens containers and enhance antibacterial effects. For example, the addition of substances such as silver ions, selenium compounds, and ammonium compounds has been reported to have antibacterial effects.

[0011] Meanwhile, a technology for a pharmaceutical composition for treating ocular diseases, which comprises a peptide with excellent antibacterial and antioxidant properties as an active ingredient, is disclosed.

[0012] However, although antimicrobial peptides are used to treat eye diseases, there have been no cases of developing antimicrobial peptides directly applied to contact lenses, and no contact lenses with semi-permanent antimicrobial and antioxidant properties have been produced to date.

[0013] The present invention was created to solve the above-mentioned problems, and provides a functional silicone hydrogel contact lens having antibacterial and antioxidant properties by coating the surface of a contact lens with a polydopamine coating solution mixed with an antibacterial peptide, thereby permanently imparting antibacterial and antioxidant properties, thereby drastically preventing bacterial infection, and by adding dopamine, a mussel-derived substance that is a biocompatible material and has excellent adhesive properties, to the coating solution, thereby enhancing the adhesiveness of the coating layer, and a method for manufacturing the same.

[0014] In addition, the present invention provides a functional silicone hydrogel contact lens having antibacterial and antioxidant properties through an antibacterial peptide surface coating that can improve the wearing comfort of contact lenses and eye diseases of wearers due to high moisture content and high oxygen permeability while increasing surface hydrophilicity during the manufacture of contact lenses, and a method for manufacturing the same, while further increasing the adhesiveness of a polydopamine coating solution due to excellent surface hydrophilicity.

[0015] The contact lens coated with dopamine and peptide of the present invention for solving the above problem comprises a contact lens formed of a hydroxyethyl methacrylate (HEMA) polymer, and a coating layer coated on the surface of the contact lens with a coating solution containing a mixture of dopamine and an antibacterial peptide.

[0016] The material of the above contact lens is composed of a mixture of 40 to 50 wt% HEMA, 0.05 to 1 wt% EGDMA, 0.1 to 2 wt% AIBN, 2 to 10 wt% MPC, 20 to 60 wt% DMA, and 5 to 15 wt% PDMS.

[0017] The above coating solution is preferably a mixture of dopamine at a concentration of 0.2 to 0.3 mg / ml and antibacterial peptide at a concentration of 0.3 to 0.7 mg / ml.

[0018] The coating time of the above coating layer is 4 to 20 hours, forming a coating thickness of 10 to 25 nm, and the coating thickness is controlled according to the temperature of the coating solution and the coating time.

[0019] The above antimicrobial peptide is preferably a mixture of tetravalent antimicrobial peptides having antibacterial, antifungal or anti-inflammatory activity of the RGRKVVRR sequence, including B4010 and B2088.

[0020] In addition, the method for manufacturing a functional silicone hydrogel contact lens having antibacterial and antioxidant properties through the surface coating of the antibacterial peptide of the present invention comprises: a coating solution manufacturing step of mixing dopamine at a concentration of 0.2 to 0.3 mg / ml and an antibacterial peptide at a concentration of 0.3 to 0.7 mg / ml to manufacture a coating solution; a washing step of washing a contact lens formed of a hydroxyethyl methacrylate (HEMA) polymer 2 to 5 times; a coating step of coating the surface of the contact lens by placing the washed contact lens in a lens tray, adding the coating solution, and stirring the solution in a shaker at 200 to 400 rpm at a temperature of 15 to 45°C; a coating surface washing step of washing the surface of the coated contact lens by placing the coated contact lens in an ethanol aqueous solution having a concentration of 10 to 20% after the coating step and ultrasonically treating the contact lens for 10 to 20 minutes; After the coating surface washing is completed, a coating surface confirmation step is performed to check the condition of the coating surface; and then a coating solution is coated on the surface of the contact lens to form a coating layer.

[0021] According to the functional silicone hydrogel contact lens having antibacterial and antioxidant properties through the antibacterial peptide surface coating of the present invention having the above-described composition, the surface of the contact lens is coated with a coating solution mixed with an antibacterial peptide, thereby providing semi-permanent antibacterial and antioxidant properties, thereby preventing or minimizing bacterial infection, and dopamine, a mussel-derived substance with excellent adhesive properties, is mixed into the coating solution, thereby increasing the adhesiveness of the coating solution, preventing it from being easily separated or falling off, and improving the quality of the product, thereby providing high reliability.

[0022] In addition, by manufacturing a contact lens having high water content and high oxygen permeability while also having high surface hydrophilicity, the wearing comfort of the contact lens and the wearer's eye diseases are improved, and the excellent surface hydrophilicity further increases the adhesiveness of the polydopamine coating solution, thereby providing excellent coating properties.

[0023] Figure 1 is a manufacturing process diagram for forming a coating layer on the surface of a contact lens according to the present invention.

[0024] Figure 2 is a graph showing the coating thickness according to the coating time of the coating solution according to the present invention.

[0025] Figure 3 is a photograph of an anaerobic fungal and aerobic bacterial culture test to confirm the antibacterial properties of a contact lens according to the present invention.

[0026] Figure 4 is a graph showing the antioxidant properties of a contact lens coated with dopamine and an antibacterial peptide according to the present invention.

[0027] Hereinafter, with reference to the attached drawings, a functional silicone hydrogel contact lens having antibacterial and antioxidant properties through an antibacterial peptide surface coating according to a preferred embodiment of the present invention and a method for manufacturing the same will be described in detail.

[0028] As shown, the functional silicone hydrogel contact lens having antibacterial and antioxidant properties through an antibacterial peptide surface coating according to the present invention includes a coating layer coated with a polydopamine coating solution in which dopamine and an antibacterial peptide are added and mixed on the surface of the contact lens.

[0029] Polydopamine exhibits excellent surface adhesion regardless of the chemical properties of various surfaces, similar to how mussels adhere to various surfaces in aquatic environments through their adhesive proteins. Polydopamine can be easily coated onto any surface and is highly biocompatible and water-dispersible.

[0030] In addition, since polydopamine can be produced into nanoparticles, it can be used as a drug delivery vehicle by carrying anticancer drugs, antibacterial drugs, etc., and can be coated on the surface of objects requiring antibacterial properties.

[0031] In the present invention, an antibacterial peptide and dopamine are added to a coating solution, and by coating the surface of a contact lens with a coating solution containing a mixture of dopamine and an antibacterial peptide, it is possible to manufacture a contact lens having semi-permanent antibacterial and antioxidant properties.

[0032] Contact lenses coated with a coating solution form a coating layer that inhibits bacterial growth, thereby preventing the occurrence of eye diseases.

[0033] Here, the above antimicrobial peptide is a mixture of a tetravalent antimicrobial peptide having the RGRKVVRR sequence including B4010 and B2088. The tetravalent antimicrobial peptide having the RGRKVVRR sequence including B4010 and B2088 is a known antimicrobial peptide used for the treatment of ocular diseases and is known to have antibacterial, antifungal, or anti-inflammatory activities.

[0034] The antibacterial peptide of the present invention is not a general peptide, but a known antibacterial peptide used for treating eye diseases, and a coating solution is prepared by mixing the peptide, and a coating layer is formed on the surface of a contact lens using the coating solution, so that no negative effects or other harmful effects occur on the human body, and it is expected that not only eye diseases can be prevented, but also treatment effects can be expected.

[0035] Figure 2 is a graph showing the coating thickness of the coating layer according to the coating time. The coating thickness was thickest when coated at room temperature (25℃) compared to low temperature (4℃) or high temperature (50℃). The coating thickness was found to increase in the order of room temperature > high temperature > low temperature.

[0036] It was confirmed that the thickness of the coating layer can be controlled by controlling the coating temperature and coating time of the above coating solution. As shown in the graph, when the coating time is less than 4 hours, the coating thickness is too thin, and when coating is performed for more than 20 hours, there is no significant change in the coating thickness even if coating is performed for a long time.

[0037] Therefore, in the present invention, the coating layer is preferably coated while stirring at 200 to 400 rpm at a temperature of 5 to 45°C, and the coating time is preferably 4 to 20 hours so that the coating thickness becomes 10 to 25 nm.

[0038] At this time, the coating solution is formed by mixing dopamine at a concentration of 0.2 to 0.3 mg / ml and peptide at a concentration of 0.3 to 0.7 mg / ml.

[0039] At dopamine concentrations below 0.2 mg / ml, coating quality issues can arise, such as improper coating or separation of the coating layer. At dopamine concentrations exceeding 0.3 mg / ml, the coating layer can become too thick, resulting in differences in prescription or changes in physical properties, potentially altering the shape of the contact lens.

[0040] And if the above antibacterial peptide is less than 0.3 mg / ml in concentration, the antibacterial and antioxidant effects are minimal, and even if the concentration exceeds 0.7 mg / ml, there is no significant difference in the antibacterial effect, so it is added at a concentration of 0.3 to 0.7 mg / ml.

[0041] Figure 3 is a photograph of an anaerobic fungal and aerobic bacterial culture test, wherein test group A is a contact lens coated with the coating solution of the present invention, and test group B is a general contact lens that is not coated.

[0042] As a result of the anaerobic fungal culture experiment in SDA, the contact lenses coated with the coating solution showed 0 CFU / unit, and the uncoated general contact lenses showed 28 CFU / unit, and as a result of the aerobic bacterial culture experiment in TSA, the contact lenses coated with the coating solution showed 3 CFU / unit, and the uncoated general contact lenses showed 51 CFU / unit, confirming that the contact lenses coated with the coating solution containing the dopamine and peptide of the present invention have antibacterial and antifungal effects.

[0043] Figure 4 is a graph showing the results of an antioxidant test of a contact lens coated with a dopamine and antibacterial peptide (B4010) coating solution, measured by a radical scavenging rate test using ascorbic acid.

[0044] The measurement results showed that all three manufactured lenses exhibited antioxidant properties almost similar to those of ascorbic acid, which has a high radical scavenging rate.

[0045] Meanwhile, in the present invention, the contact lens is formed of a hydroxyethyl methacrylate (HEMA) polymer, and various functional monomers are added to increase the surface hydrophilicity while ensuring high moisture content and high oxygen permeability, thereby increasing the adhesiveness of the coating solution.

[0046] Specifically, the material of the contact lens is manufactured by mixing an acrylic monomer and a silicone monomer, and specifically, HEMA, EGDMA, AIBN, PDMS, MPC, and DMA are added and mixed.

[0047] The mixing amount of the contact lens polymer is preferably a mixture of 40 to 50 wt% of HEMA, 0.05 to 1 wt% of EGDMA, 0.1 to 2 wt% of AIBN, 2 to 10 wt% of MPC, 20 to 60 wt% of DMA, and 5 to 15 wt% of PDMS.

[0048] The above EGDMA acts as a crosslinking agent for synthesizing each component, and if too much is added, polymer synthesis may occur excessively, causing HEMA, an acrylic monomer, and PDMS, a silicone monomer, to become integrated, and if too little is added, the content may be minimal, preventing proper synthesis or bonding between each component.

[0049] PDMS is a material added to increase oxygen permeability. If PDMS is mixed in less than 5 wt%, the value is insufficient and it is difficult to obtain the expected oxygen permeability. If it is mixed in more than 15 wt%, too much is added, so PDMS does not dissolve properly and does not mix effectively with other materials, but separates, causing a cloudy, stain-like phenomenon.

[0050] The above MPC and DMA are both hydrophilic monomers and biocompatible materials, which increase the surface hydrophilicity and wettability of the contact lens. Accordingly, the adhesiveness of the polydopamine coating solution is increased, which significantly increases the coating efficiency by preventing it from easily detaching from the contact lens surface and maintaining the coating state.

[0051] In addition, since MPC and DMA are basically biocompatible materials, they have antifouling and antibacterial properties for contact lenses. In addition, in the present invention, since they are coated with a polydopamine coating solution, they have semi-permanent antibacterial and antioxidative properties.

[0052] As described above, the coating process of a contact lens coated with the coating solution of the present invention forms a coating layer through a coating solution preparation step, a contact lens washing step, a coating step, a coating surface washing step, and a coating surface confirmation step.

[0053] The coating solution is manufactured by mixing dopamine at a concentration of 0.2 to 0.3 mg / ml and an antibacterial peptide at a concentration of 0.3 to 0.7 mg / ml to manufacture a polydopamine coating solution.

[0054] Contact lenses are manufactured by mixing 40 to 50 wt% HEMA, 0.05 to 1 wt% EGDMA, 0.1 to 2 wt% AIBN, 2 to 10 wt% MPC, 20 to 60 wt% DMA, and 5 to 15 wt% PDMS and going through a polymerization process. Contact lenses manufactured in this manner are washed 2 to 5 times with DI water.

[0055] In the coating step, after placing the washed contact lenses in a lens tray, a polydopamine coating solution is added and the contact lens surface is coated while stirring in a shaker at 200 to 400 rpm at a temperature of 15 to 45°C.

[0056] After coating, the coated contact lens is placed in a 10-20% ethanol solution and then goes through a cleaning step where the surface of the coated contact lens is cleaned by ultrasonic treatment for 10-20 minutes.

[0057] Once the coating surface has been washed, a coating surface check step is performed to check the condition of the coating surface.

[0058] For example, after cleaning with ultrasonic treatment for 10 minutes, check the coating surface. If the coating surface is clean, cleaning is complete. If it is not cleaned properly or requires more cleaning, wash for a few more minutes.

[0059] The above steps are followed to form a coating layer by coating a polydopamine coating solution on the surface of a contact lens.

Claims

1. Contact lenses formed from hydroxyethyl methacrylate (HEMA) polymers, A functional silicone hydrogel contact lens having antibacterial and antioxidant properties through an antibacterial peptide surface coating, characterized in that the surface of the contact lens is coated with a coating layer containing a coating solution containing a mixture of dopamine and an antibacterial peptide.

2. In paragraph 1, The material of the above contact lens is a functional silicone hydrogel contact lens having antibacterial and antioxidant properties through an antibacterial peptide surface coating, characterized in that the contact lens material is composed of a mixture of 40 to 50 wt% HEMA, 0.05 to 1 wt% EGDMA, 0.1 to 2 wt% AIBN, 2 to 10 wt% MPC, 20 to 60 wt% DMA, and 5 to 15 wt% PDMS.

3. In paragraph 1, A functional silicone hydrogel contact lens having antibacterial and antioxidant properties through an antibacterial peptide surface coating characterized in that the coating solution is a mixture of dopamine at a concentration of 0.2 to 0.3 mg / ml and an antibacterial peptide at a concentration of 0.3 to 0.7 mg / ml.

4. In paragraph 3, A functional silicone hydrogel contact lens having antibacterial and antioxidant properties through an antibacterial peptide surface coating characterized in that the above antibacterial peptide is a mixture of tetravalent antibacterial peptides having antibacterial, antifungal or anti-inflammatory activities of the RGRKVVRR sequence, including B4010 and B2088.

5. In paragraph 1, A functional silicone hydrogel contact lens having antibacterial and antioxidant properties through an antibacterial peptide surface coating, characterized in that the coating solution is stirred at 200 to 400 rpm at a temperature of 15 to 45°C.

6. In paragraph 1, A functional silicone hydrogel contact lens having antibacterial and antioxidant properties through an antibacterial peptide surface coating, characterized in that the coating time of the above coating layer is 4 to 20 hours, forming a coating thickness of 10 to 25 nm, and the coating thickness is controlled according to the temperature and coating time of the coating solution. A coating solution manufacturing step for manufacturing a polydopamine coating solution by mixing dopamine at a concentration of 0.2 to 0.3 mg / ml and an antibacterial peptide at a concentration of 0.3 to 0.7 mg / ml; A washing step for washing contact lenses formed of hydroxyethyl methacrylate (HEMA) polymers 2 to 5 times; A coating step in which a washed contact lens is placed in a lens tray, a polydopamine coating solution is added, and the solution is stirred in a shaker at 200 to 400 rpm at a temperature of 15 to 45°C to coat the surface of the contact lens; A coating surface washing step in which the coated contact lens is placed in an ethanol aqueous solution with a concentration of 10 to 20% after the coating step and then the surface of the coated contact lens is washed by ultrasonic treatment for 10 to 20 minutes; Coating surface confirmation step to check the condition of the coating surface after the coating surface washing is completed; A method for manufacturing a functional silicone hydrogel contact lens having antibacterial and antioxidant properties through an antibacterial peptide surface coating, characterized in that a polydopamine coating solution is coated on the surface of the contact lens to form a coating layer.

8. In paragraph 7, A method for manufacturing a functional silicone hydrogel contact lens having antibacterial and antioxidant properties through an antibacterial peptide surface coating, characterized in that the contact lens is manufactured by mixing 40 to 50 wt% of HEMA, 0.05 to 1 wt% of EGDMA, 0.1 to 2 wt% of AIBN, 2 to 10 wt% of MPC, 20 to 60 wt% of DMA, and 5 to 15 wt% of PDMS and going through a polymerization process.

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