Method for manufacturing artificial cornea using interfacial adhesion between optical unit and support unit having different properties

Abstract

The present invention relates to a method for manufacturing an artificial cornea exhibiting excellent physical properties by stably adhering an interface between an optical unit and a support unit by means of an artificial cornea mold and UV dose modulation. According to the present invention, an optical unit is manufactured for one to four hours using low-dose UV in an artificial cornea mold so as to stably adhere an interface between an optical unit and a support unit, thereby manufacturing an artificial cornea in which the optical unit and the support unit are integrated with each other. The artificial cornea manufactured by the manufacturing method has a consistent spherical shape, which is convenient for centering and increases surgical success rates during surgery, the central part of the optical unit exhibits uniform and excellent physical properties to further increase physical safety in the human body, and the boundary surface between the optical unit and the support unit exhibits about 100 times more excellent physical properties compared to existing intraocular pressure, thus allowing early prevention of the optical unit and the support unit separating due to intraocular pressure in the human body. In addition, the manufacturing method can improve the appearance of a patient implanted with an artificial cornea and reduce complications and side effects caused by adhesive material.

Description

Method for manufacturing an artificial cornea using interfacial adhesion of optical and support parts with different properties

[0001] The present invention relates to a method for manufacturing an artificial cornea exhibiting excellent physical properties by stably bonding the interface between an optical part and a support part.

[0002]

[0003] An artificial cornea is a device used for patients with damaged corneas. It requires an optical component (core) to secure vision and a supporting component (skirt) to securely attach the optical component to the eye. The optical component is colorless and transparent, with a visible light transmittance of over 99%, replacing the damaged cornea and allowing light to pass through. The supporting component is an opaque white cell-supporting structure that secures the artificial cornea to the eye through autologous cell proliferation.

[0004] Current technology lacks a simple method for bonding the optics and support elements. Therefore, methods such as inserting the cornea between metal and plastic to secure it, or using nylon sutures to join the optics and support elements have been used. However, these methods are complex to manufacture, which increases the size of the product. This can lead to a different appearance of the eye after corneal surgery, which can lower the patient's self-esteem and social functioning. Furthermore, these methods utilize metal and sutures, not the materials required for an artificial cornea, which increases the risk of infection after surgery.

[0005] To solve this problem, the academic world has proposed several methods, such as plasma techniques and graft polymerization, for interfacial bonding between the optical and support parts. However, these methods only provide a small amount of adhesiveness between the interfaces, and show properties that are lower than the physical properties of the optical and support parts, which limits their application to actual products.

[0006] Therefore, there is a need to develop a technology applicable to an artificial cornea that can improve the patient's appearance and reduce complications and side effects caused by adhesive materials by enabling the adhesion of the optical part and the support part without using other materials.

[0007] Additionally, the artificial cornea procedure involves making a semicircular incision in the anterior layer of the cornea, then removing a 3.5 to 5.5 mm disk of the posterior layer to remove the clouded cornea. The center of the posterior layer and the center of the artificial cornea are adjusted to be as centered as possible, and the anterior layer is covered and the field of vision is secured through an incision in the anterior layer. If the artificial cornea is not precisely centered during this process, it may not align with the underlying cornea at the designed radius of curvature, which can cause secondary side effects, and there is a possibility that light may not be refracted as intended, preventing the image from being formed on the crystalline lens. In more severe cases, there is also a risk of the artificial cornea leaking into the resected anterior layer.

[0008] Accordingly, the development of technology to stabilize the shape of the artificial cornea so that it can be used as designed is also required.

[0009]

[0010] [Prior Art Literature]

[0011] [Patent Document]

[0012] (Patent Document 1) KR 10-2016-0140687 (2016-10-27)

[0013]

[0014] The present inventors have made great efforts to provide a method for manufacturing an artificial cornea that can provide a stabilized shape and excellent physical properties while simultaneously bonding an optical part and a support part without using other materials. As a result, they have confirmed that when only a part of the optical part is manufactured by photopolymerization and the remaining part of the optical part together with the support part is manufactured by thermal polymerization, a double network is formed between the interface of the optical part and the support part to provide adhesiveness, thereby manufacturing an artificial cornea with excellent physical properties, and have completed the present invention.

[0015]

[0016] Accordingly, the purpose of the present invention is to provide a method for manufacturing an artificial cornea that exhibits a stabilized shape and excellent physical properties by stably bonding the interface between the optical part and the support part.

[0017]

[0018] The present invention comprises the steps of: i) irradiating a mixture of an acrylic monomer, a photoinitiator, a crosslinking agent, methanol, and distilled water with UV of 5 to 40 W and 300 to 400 nm for 1 to 4 hours to photopolymerize the mixture, thereby manufacturing an optical part; and

[0019] ii) a step of adding a mixture of an acrylic monomer, distilled water, dimethylformamide, a crosslinking agent, a thermal initiator, and N,N,N'N' tetramethylethylenediamine to the optical part manufactured above and thermally polymerizing it at 30 to 100°C for 30 minutes to 2 hours to manufacture a support part bonded to the optical part;

[0020] A method for manufacturing an artificial cornea comprising an optical part and a support part is provided.

[0021] According to a preferred embodiment of the present invention, the acrylic monomer of step i) is mixed in an amount of 70 to 90 wt%, the photoinitiator is mixed in an amount of 0.1 to 3 wt% based on the monomer, and the crosslinking agent is mixed in an amount of 0.1 to 0.3 wt% based on the monomer.

[0022] According to a preferred embodiment of the present invention, the acrylic monomer of step ii) is mixed in an amount of 15 to 35 wt%, the crosslinking agent is mixed in an amount of 1 to 3 wt% based on the monomer, the thermal initiator is mixed in an amount of 3 to 6 wt% based on the monomer, and N,N,N'N' tetramethylethylenediamine is mixed in an amount of 2 to 4 wt% based on the monomer.

[0023] According to a preferred embodiment of the present invention, the acrylic monomer is at least one selected from the group consisting of methyl methacrylate, 2-hydroxyethyl methacrylate, trimethylolpropane triacrylate, 1,4-butanediol diacrylate, ethylhexyl acrylate, glycidyl methacrylate, ethyleneglycol dimethacrylate, and 1,6-hexanediol diacrylate.

[0024] According to a preferred embodiment of the present invention, the photoinitiator of step i) is at least one selected from the group consisting of 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone, 1-hydroxy-cyclohexyl-phenyl-ketone, and bis(2,4,6-trimethylbenzoyl)-phenylphosphineoxide.

[0025] According to a preferred embodiment of the present invention, the crosslinking agent of step i) is at least one selected from the group consisting of pentaerythritol tetraacrylate, pentaerythritol triacrylate, N,N'-methylenebisacrylamide, and ethylene glycol dimethacrylate (EGDMA).

[0026] According to a preferred embodiment of the present invention, the distilled water and methanol of step i) are mixed in a weight ratio of 75 to 95:5 to 25.

[0027] According to a preferred embodiment of the present invention, in step i), only 80 to 99% of the optical portion is manufactured by photopolymerization.

[0028] According to a preferred embodiment of the present invention, the distilled water and dimethylformamide of step ii) are mixed in a weight ratio of 70 to 90:10 to 30.

[0029] According to a preferred embodiment of the present invention, the crosslinking agent of step ii) is at least one selected from the group consisting of pentaerythritol tetraacrylate, pentaerythritol triacrylate, N,N'-methylenebisacrylamide, and ethylene glycol dimethacrylate (EGDMA).

[0030] According to a preferred embodiment of the present invention, the thermal initiator of step ii) is ammonium persulfate and / or potassium persulfate.

[0031] In addition, the present invention provides an artificial cornea manufactured by the above manufacturing method.

[0032] According to a preferred embodiment of the present invention, the tensile strength of the interface between the optical portion and the support portion of the artificial cornea is 100 to 200 KPa.

[0033] According to a preferred embodiment of the present invention, the overall diameter of the artificial cornea is 7 to 9 mm, the optical diameter is 3 to 6 mm, and the apex thickness is 0.4 to 0.6 mm.

[0034] According to a preferred embodiment of the present invention, the radius of curvature of the artificial cornea is 7.5 to 8.0 mm at the front and 6.0 to 7.0 mm at the back.

[0035] In addition, the present invention comprises the steps of: i) dispensing a mixture of an acrylic monomer, a photoinitiator, a crosslinking agent, methanol, and distilled water into a lower mold, then combining the upper mold, irradiating the mixture with UV of 5 to 40 W and 300 to 400 nm for 1 to 4 hours, and photopolymerizing to manufacture an optical part; and

[0036] ii) A step of manufacturing a support portion bonded to the optical portion by injecting a mixture of an acrylic monomer, distilled water, dimethylformamide, a crosslinking agent, a thermal initiator, and N,N,N'N' tetramethylethylenediamine into the lower mold in which the optical portion is formed, and then thermally polymerizing the mixture at 30 to 100°C for 30 minutes to 2 hours;

[0037] A method for manufacturing an artificial cornea comprising an optical part and a support part is provided.

[0038] According to a preferred embodiment of the present invention, step ii) is performed continuously without separating the upper mold and the lower mold.

[0039]

[0040] The optical and support components can typically be integrated using bioadhesives or sutures. However, because the artificial cornea is a soft tissue, flexible rather than rigid, the use of bioadhesives can result in partial instability at the bonding site. Furthermore, the narrow surface area of ​​sutures can lead to tearing of the artificial cornea. Furthermore, the use of additional materials for fusion can increase the risk of infection and unnecessary surgical procedures.

[0041] Additionally, when the inventors of the present invention manufactured an artificial cornea using high-energy UV, the center of the artificial cornea did not align (Fig. 5b). This was because the reaction occurred unevenly during photopolymerization using a high-energy UV lamp, causing deformation of the optical part shape.

[0042] Accordingly, the inventors of the present invention changed the polymerization conditions of the optical part to fuse the optical part and the support part, and simultaneously polymerized the optical part and the support part during the polymerization process to manufacture an artificial cornea. In the present invention, the degree of polymerization was controlled differently in the central part (80% to 99%) and the peripheral part (1% to 20%) of the optical part by irradiating them with low-intensity light. The central part of the optical part, which was intensively exposed to low-intensity light, had a polymerization degree of 100%, which did not affect the transparency and physical properties for securing a field of vision, and the peripheral part, which was relatively less exposed to light, was polymerized only at the oligomer level and had liquid properties. Thereafter, when the support part solution was introduced, it was mixed with the peripheral part of the optical part, and the peripheral part of the optical part was further thermally polymerized together with the support part due to the thermal initiator (APS) in the support part solution. Finally, the peripheral part of the optical part and the support part solution were polymerized simultaneously and fused in the form of a double network to form an artificial cornea.

[0043] When an artificial cornea is manufactured by the method of the present invention, the interface between the optical portion and the support portion can be bonded, the interface tensile strength is high, and it exhibits superior physical properties compared to bonding using oxygen plasma, which is a general method for bonding different interfaces. In addition, the support portion of the present invention has a rough surface shape due to the form of woven beads, and is provided with porosity, which is optimized for cell growth. In particular, the artificial cornea manufactured by the method of the present invention can be bonded to the eye using a cell support without using sutures, thereby minimizing secondary infection and foreign body reaction caused by sutures. In addition, since it has a structure in which autologous cells infiltrate the cell support and grow on their own, it can minimize immune rejection reactions.

[0044] Additionally, when manufacturing an artificial cornea using the method of the present invention, it was confirmed that the central portion (center) of the artificial cornea was aligned. This was because UV light of low energy was irradiated to the central portion, thereby forming a uniform reaction.

[0045] On the other hand, when the optical part and the support part were polymerized separately using 40 W high-energy UV, the optical part was not fused with the support solution after 100% polymerization, so it was confirmed that the interface between the optical part and the support part was not bonded in the actual SEM image, and the interfacial tensile strength and physical properties were very low.

[0046]

[0047] Accordingly, the present invention comprises the steps of: i) irradiating a mixture of an acrylic monomer, a photoinitiator, a crosslinking agent, methanol, and distilled water with UV of 5 to 40 W and 300 to 400 nm for 1 to 4 hours to photopolymerize the mixture to manufacture an optical part; and

[0048] ii) A step of manufacturing a support part bonded to the optical part by adding a mixture of an acrylic monomer, distilled water, dimethylformamide, a crosslinking agent, a thermal initiator, and N,N,N'N' tetramethylethylenediamine to the manufactured optical part and thermally polymerizing it at 30 to 100°C for 30 minutes to 2 hours;

[0049] A method for manufacturing an artificial cornea comprising an optical part and a support part can be provided.

[0050] Preferably, the photopolymerization of step i) may be performed by irradiating with UV of 7 to 10 W and 350 to 380 nm for 2 to 3 hours, and the thermal polymerization of step ii) may be performed at 30 to 40°C for 50 to 70 minutes.

[0051] In the above step i), if UV (ultraviolet) is irradiated for less than 1 hour, a polymer is not formed, so sufficient physical properties of the optical part cannot be maintained, and if irradiated for more than 4 hours, the optical part may be completely polymerized (solidified), so adhesion between the optical part and the support part may not be achieved.

[0052] The N,N,N'N' tetramethylethylenediamine of step ii) above may be included to control the reaction rate of the interface.

[0053] According to a preferred embodiment of the present invention, the acrylic monomer of step i) may be mixed in an amount of 70 to 90 wt%, the photoinitiator in an amount of 0.1 to 3 wt% based on the monomer, and the crosslinking agent in an amount of 0.1 to 0.3 wt% based on the monomer, and the acrylic monomer of step ii) may be mixed in an amount of 15 to 35 wt%, the crosslinking agent in an amount of 1 to 3 wt% based on the monomer, the thermal initiator in an amount of 3 to 6 wt% based on the monomer, and N,N,N'N' tetramethylethylenediamine in an amount of 2 to 4 wt% based on the monomer.

[0054] Preferably, the acrylic monomer of step i) may be included in an amount of 75 to 85 wt%, and the acrylic monomer of step ii) may be included in an amount of 20 to 30 wt%.

[0055] According to a preferred embodiment of the present invention, the acrylic monomer may be at least one selected from the group consisting of methyl methacrylate, 2-hydroxyethyl methacrylate, trimethylolpropane triacrylate, 1,4-butanediol diacrylate, ethylhexyl acrylate, glycidyl methacrylate, ethyleneglycol dimethacrylate, and 1,6-hexanediol diacrylate. Preferably, the acrylic monomer may be methyl methacrylate and 2-hydroxyethyl methacrylate.

[0056] Specifically, the acrylic monomer of step i) may include 2-hydroxyethyl methacrylate and methyl methacrylate in a ratio of 8 to 10: 1 to 2, and the acrylic monomer of step ii) may include 2-hydroxyethyl methacrylate and methyl methacrylate in a ratio of 7 to 10: 1 to 3.

[0057] When the photoinitiator content of the above step i) is less than 0.1 wt% relative to the monomer, polymerization of the monomer does not occur, and when it exceeds 3 wt% relative to the monomer, the reaction progresses rapidly, so that all optical parts are polymerized, and the effect of forming a polymer-oligomer according to the UV intensity is insignificant, so that adhesion due to photopolymerization and thermal polymerization does not occur.

[0058] According to a preferred embodiment of the present invention, the photoinitiator of step i) includes any substance containing a hydroxy alkyl ketone group, but preferably, it may be at least one selected from the group consisting of 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone (Irgacure 2959), 1-hydroxy-cyclohexyl-phenyl-ketone (Irgacure 184), and bis(2,4,6-trimethylbenzoyl)-phenylphosphineoxide (Irgacure 819). More preferably, the photoinitiator of step i) may be 2-Hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone (Irgacure 2959).

[0059] If the content of the crosslinking agent in step i) above is less than 0.1 wt% based on the monomer, the optical part may have flowability and may detach from the surgical site, and the swelling may increase, making it difficult to control the thickness or diameter, etc., and if it exceeds 0.3 wt% based on the monomer, the flexibility of the optical part may decrease and there is a risk of it being easily broken, and the light transmittance may decrease due to crystallization.

[0060] According to a preferred embodiment of the present invention, the crosslinking agent of step i) is at least one selected from the group consisting of pentaerythritol tetraacrylate, pentaerythritol triacrylate, N,N'-methylenebisacrylamide, and ethylene glycol dimethacrylate (EGDMA). Preferably, the crosslinking agent of step i) may be ethylene glycol dimethacrylate (EGDMA).

[0061] According to a preferred embodiment of the present invention, the distilled water and methanol of step i) may be mixed in a weight ratio of 75 to 95: 5 to 25. Preferably, the distilled water and ethanol of step i) may be mixed in a weight ratio of 80 to 90: 10 to 20.

[0062] According to a preferred embodiment of the present invention, in step i), only 80 to 99% of the optical portion is manufactured by photopolymerization.

[0063] According to a preferred embodiment of the present invention, the distilled water and dimethylformamide of step ii) may be mixed in a weight ratio of 70 to 90:10 to 30. Preferably, the distilled water and dimethylformamide of step ii) may be mixed in a weight ratio of 75 to 85:15 to 25.

[0064] According to a preferred embodiment of the present invention, the crosslinking agent of step ii) may be at least one selected from the group consisting of pentaerythritol tetraacrylate, pentaerythritol triacrylate, N,N'-methylenebisacrylamide, and ethylene glycol dimethacrylate (EGDMA). Preferably, the crosslinking agent of step ii) may be pentaerythritol tetraacrylate.

[0065] According to a preferred embodiment of the present invention, the thermal initiator of step ii) is ammonium persulfate and / or potassium persulfate. Preferably, the thermal initiator of step ii) may be ammonium persulfate.

[0066] The above thermal initiator may be included in an amount of 1 to 10 wt% relative to the monomer, and preferably 3 to 6 wt%. If the thermal initiator is included in an amount of less than 3 wt% relative to the monomer, polymerization of the interface is not formed, and if the thermal initiator is included in an amount of 6 wt% or more relative to the monomer, the thermal initiator may affect the physical properties of the support.

[0067]

[0068] In addition, the present invention provides an artificial cornea manufactured by the above manufacturing method.

[0069] According to a preferred embodiment of the present invention, the tensile strength of the interface between the optical portion and the support portion of the artificial cornea is 100 to 200 KPa.

[0070] According to a preferred embodiment of the present invention, the overall diameter of the artificial cornea is 7 to 9 mm, the optical diameter is 3 to 6 mm, and the apex thickness is 0.4 to 0.6 mm.

[0071] According to a preferred embodiment of the present invention, the radius of curvature of the artificial cornea is 7.5 to 8.0 mm at the front and 6.0 to 7.0 mm at the back.

[0072]

[0073] In addition, the present invention comprises the steps of: i) dispensing a mixture of an acrylic monomer, a photoinitiator, a crosslinking agent, methanol, and distilled water into a lower mold, then combining the upper mold, irradiating the mixture with UV of 5 to 40 W and 300 to 400 nm for 1 to 4 hours, and photopolymerizing to manufacture an optical part; and

[0074] ii) A step of manufacturing a support portion bonded to the optical portion by injecting a mixture of an acrylic monomer, distilled water, dimethylformamide, a crosslinking agent, a thermal initiator, and N,N,N'N' tetramethylethylenediamine into the lower mold in which the optical portion is formed, and then thermally polymerizing the mixture at 30 to 100°C for 30 minutes to 2 hours;

[0075] A method for manufacturing an artificial cornea comprising an optical part and a support part is provided.

[0076] Preferably, the photopolymerization of step i) may be performed by irradiating with UV of 7 to 10 W and 350 to 380 nm for 2 to 3 hours, and the thermal polymerization of step ii) may be performed at 30 to 40°C for 50 to 70 minutes.

[0077] In the above step i), if UV (ultraviolet) is irradiated for less than 1 hour, a polymer is not formed, and thus sufficient physical properties of the optical portion cannot be maintained. The target thickness of the optical portion is 0.5 mm, which is most similar to the human body, but if photopolymerized for less than 1 H, the thickness may decrease to less than 0.3 mm. On the other hand, if irradiated for more than 4 hours, the optical portion may be completely polymerized (solidified), and adhesion between the optical portion and the support portion may not occur (Fig. 4b).

[0078] The N,N,N'N' tetramethylethylenediamine of step ii) above may be included to control the reaction rate of the interface.

[0079] According to a preferred embodiment of the present invention, the acrylic monomer of step i) may be mixed in an amount of 70 to 90 wt%, the photoinitiator in an amount of 0.1 to 3 wt% based on the monomer, and the crosslinking agent in an amount of 0.1 to 0.3 wt% based on the monomer, and the acrylic monomer of step ii) may be mixed in an amount of 15 to 35 wt%, the crosslinking agent in an amount of 1 to 3 wt% based on the monomer, the thermal initiator in an amount of 3 to 6 wt% based on the monomer, and N,N,N'N' tetramethylethylenediamine in an amount of 2 to 4 wt% based on the monomer.

[0080] Preferably, the acrylic monomer of step i) may be included in an amount of 75 to 85 wt%, and the acrylic monomer of step ii) may be included in an amount of 20 to 30 wt%.

[0081] According to a preferred embodiment of the present invention, the acrylic monomer may be at least one selected from the group consisting of methyl methacrylate, 2-hydroxyethyl methacrylate, trimethylolpropane triacrylate, 1,4-butanediol diacrylate, ethylhexyl acrylate, glycidyl methacrylate, ethyleneglycol dimethacrylate, and 1,6-hexanediol diacrylate. Preferably, the acrylic monomer may be methyl methacrylate and 2-hydroxyethyl methacrylate.

[0082] Specifically, the acrylic monomer of step i) may include 2-hydroxyethyl methacrylate and methyl methacrylate in a ratio of 8 to 10: 1 to 2, and the acrylic monomer of step ii) may include 2-hydroxyethyl methacrylate and methyl methacrylate in a ratio of 7 to 10: 1 to 3.

[0083] When the photoinitiator content of the above step i) is less than 0.1 wt% relative to the monomer, polymerization of the monomer does not occur, and when it exceeds 3 wt% relative to the monomer, the reaction progresses rapidly, so that all optical parts are polymerized, and the effect of forming a polymer-oligomer according to the UV intensity is insignificant, so that adhesion due to photopolymerization and thermal polymerization does not occur.

[0084] According to a preferred embodiment of the present invention, the photoinitiator of step i) includes any substance containing a hydroxy alkyl ketone group, but preferably, it may be at least one selected from the group consisting of 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone (Irgacure 2959), 1-hydroxy-cyclohexyl-phenyl-ketone (Irgacure 184), and bis(2,4,6-trimethylbenzoyl)-phenylphosphineoxide (Irgacure 819). More preferably, the photoinitiator of step i) may be 2-Hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone (Irgacure 2959).

[0085] If the content of the crosslinking agent in step i) above is less than 0.1 wt% based on the monomer, the optical part may have flowability and may detach from the surgical site, and the swelling may increase, making it difficult to control the thickness or diameter, etc., and if it exceeds 0.3 wt% based on the monomer, the flexibility of the optical part may decrease and there is a risk of it being easily broken, and the light transmittance may decrease due to crystallization.

[0086] According to a preferred embodiment of the present invention, the crosslinking agent of step i) is at least one selected from the group consisting of pentaerythritol tetraacrylate, pentaerythritol triacrylate, N,N'-methylenebisacrylamide, and ethylene glycol dimethacrylate (EGDMA). Preferably, the crosslinking agent of step i) may be ethylene glycol dimethacrylate (EGDMA).

[0087] According to a preferred embodiment of the present invention, the distilled water and methanol of step i) may be mixed in a weight ratio of 75 to 95: 5 to 25. Preferably, the distilled water and ethanol of step i) may be mixed in a weight ratio of 80 to 90: 10 to 20.

[0088] According to a preferred embodiment of the present invention, in step i), only 80 to 99% of the optical portion is manufactured by photopolymerization.

[0089] According to a preferred embodiment of the present invention, the distilled water and dimethylformamide of step ii) may be mixed in a weight ratio of 70 to 90:10 to 30. Preferably, the distilled water and dimethylformamide of step ii) may be mixed in a weight ratio of 75 to 85:15 to 25.

[0090] According to a preferred embodiment of the present invention, the crosslinking agent of step ii) may be at least one selected from the group consisting of pentaerythritol tetraacrylate, pentaerythritol triacrylate, N,N'-methylenebisacrylamide, and ethylene glycol dimethacrylate (EGDMA). Preferably, the crosslinking agent of step ii) may be pentaerythritol tetraacrylate.

[0091] According to a preferred embodiment of the present invention, the thermal initiator of step ii) is ammonium persulfate and / or potassium persulfate. Preferably, the thermal initiator of step ii) may be ammonium persulfate.

[0092] The above thermal initiator may be included in an amount of 1 to 10 wt% relative to the monomer, and preferably 3 to 6 wt%. If the thermal initiator is included in an amount of less than 3 wt% relative to the monomer, polymerization of the interface is not formed, and if the thermal initiator is included in an amount of 6 wt% or more relative to the monomer, the thermal initiator may affect the physical properties of the support.

[0093] According to a preferred embodiment of the present invention, step ii) may be performed continuously without separating the upper mold and the lower mold.

[0094]

[0095] In addition, the mold for manufacturing an artificial cornea used in the manufacturing method of the present invention includes an upper mold (10) and a lower mold (20) so that the optical part and the support part of the artificial cornea can be manufactured continuously within one mold, and so that photopolymerization and thermal polymerization can be performed simultaneously. A first hole (11) is formed in the central portion of the upper mold (10), and a solution (12) for forming the optical part can be inserted into the first hole (11), and a second hole (13) for injecting a thermosetting solution for forming the support part can be formed in the peripheral portion of the upper mold (10). In addition, a plurality of lower fitting protrusions (21) for combining with the upper mold (10) can be formed in the lower mold (20).

[0096] The upper and lower molds are made of quartz and anodized aluminum.

[0097] The above quartz has a curvature radius of 6.5 mm for the lower quartz and 7.8 mm for the upper quartz, which is the radius of curvature used to manufacture the actual artificial cornea, so that it can implement a curvature similar to the curvature radius of the human body. The curvature characteristic of quartz is applied to the optical part of the artificial cornea so that it can be naturally integrated with the original cornea when inserted into the human body, and it has an optimized structure that can withstand intraocular pressure due to the curvature of the human body.

[0098] Because the quartz is very small, measuring 4-6 mm, the addition of the anodized aluminum facilitates handling for fastening and separating the upper and lower molds. Furthermore, by forming insertion protrusions around the periphery of the upper and lower molds, the thickness of the artificial cornea can be adjusted to 0.5 mm.

[0099] Aluminum boasts superior corrosion and oxidation resistance compared to other metals, making it immune to chemical corrosion. To further enhance corrosion and wear resistance, a 25μm anodizing coating was applied.

[0100]

[0101] The present invention can manufacture an artificial cornea in which the optical part and the support part are integrated by stably bonding the interface between the optical part and the support part by manufacturing the optical part for 1 to 4 hours using low-dose UV. The artificial cornea manufactured by the above manufacturing method has a consistent spherical shape, which can increase the success rate of the surgery by making centering easy, and the center of the optical part exhibits uniform and excellent physical properties, which can further increase the physical safety within the human body. In addition, the boundary between the optical part and the support part exhibits excellent physical properties about 100 times that of existing intraocular pressure, which can prevent the early separation of the optical part and the support part due to intraocular pressure within the human body. In addition, the above manufacturing method can improve the appearance of patients who have received an artificial cornea transplant and reduce complications and side effects caused by the adhesive material.

[0102]

[0103] Figure 1 shows the artificial cornea surgery process.

[0104] Figure 2a shows the optical part of an artificial cornea manufactured by irradiating it with 8W UV for 2 hours.

[0105] Figure 2b shows that the degree of polymerization was formed differently in the central (80% to 99%) and peripheral (1% to 20%) optical portions of an artificial cornea manufactured by irradiating it with 8 W UV for 2 hours. The central portion of the optical portion was 100% polymerized, while the peripheral portion was polymerized only at the oligomer level.

[0106] Figure 3 shows an artificial cornea manufactured by irradiating it with 8W UV for 2 hours.

[0107] Figure 4a shows the change in optical part shape according to UV irradiation time.

[0108] Figure 4b shows the appearance of an artificial cornea manufactured by photopolymerization for more than 4 hours.

[0109] Figure 5a shows the optical part of an artificial cornea manufactured by irradiating it with high-energy UV of 40 W for 2 hours.

[0110] Figure 5b shows an artificial cornea manufactured by irradiating it with high-energy UV of 40 W for 2 hours.

[0111] Figure 6 shows an artificial cornea in which an optical part and a support part are bonded using oxygen plasma.

[0112] Figure 7a shows an SEM image of an artificial cornea manufactured by irradiating it with 8W UV for 2 hours. The bead-woven structure and roughened the surface shape to increase cell adhesion.

[0113] Figure 7b shows the BCS Technology (Beads Chain Scaffold) used in the support of the artificial cornea of ​​the present invention.

[0114] Figure 8 shows an SEM image of an artificial cornea manufactured by irradiating it with 40 W of UV for 2 hours.

[0115] Figure 9 shows the tensile strength SS curves of artificial corneas manufactured by photopolymerization and thermal polymerization (UV Polymerization + Thermopolymerization), photopolymerization and oxygen plasma (UV Polymerization + Oxygen Plasma), and photopolymerization (UV Polymerization) manufacturing methods alone.

[0116] Figure 10a shows the initial elastic modulus and maximum tensile strength of artificial corneas manufactured by photopolymerization and thermal polymerization (UV Polymerization / Thermopolymerization), photopolymerization and oxygen plasma (UV Polymerization / Oxygen Plasma), and photopolymerization (UV Polymerization) manufacturing methods alone.

[0117] Figure 10b shows the maximum tensile strength of an artificial cornea manufactured according to the manufacturing method of the present invention. It was confirmed that the physical strength of the interface had superior optical-support interface properties (170 KPa) than the support strength through the interfacial bonding between the optical portion (1390 KPa) and the support portion (40 KPa).

[0118] Figure 10c shows the maximum tensile strength of an artificial cornea photopolymerized using 40 W high-energy UV light. It was confirmed that weak bonding occurred, with the maximum tensile strength at the interface being approximately 10 KPa.

[0119] Figure 10d shows the maximum tensile strength of five optical parts of an artificial cornea using high-energy UV of 40 W (Sample 1: 1416 KPa, Sample 2: 1046 KPa, Sample 3: 1532 KPa, Sample 4: 957 KPa, Sample 5: 1042 KPa). It can be seen that the standard deviation is very large.

[0120] Figure 10e shows the maximum tensile strength of five optical parts of an artificial cornea manufactured according to the manufacturing method of the present invention (Sample 1: 1398 KPa, Sample 2: 1351 KPa, Sample 3: 1431 KPa, Sample 4: 1356 KPa, Sample 5: 1344 KPa). It was confirmed that a uniform tensile strength was exhibited.

[0121] Figure 11a shows a mold for manufacturing an artificial cornea to which the method for manufacturing an artificial cornea of ​​the present invention can be applied.

[0122] Fig. 11b illustrates a mold for manufacturing an artificial cornea to which the method for manufacturing an artificial cornea of ​​the present invention can be applied. A first hole (11) is formed in the central portion of the upper mold (10), and a solution (12) for forming an optical portion can be inserted into the first hole (11), and a second hole (13) for injecting a solution for forming a support portion can be formed in the peripheral portion of the upper mold (10). In addition, a plurality of lower fitting protrusions (21) for joining with the upper mold (10) can be formed in the lower mold (20).

[0123] Figure 11c illustrates a mold for manufacturing an artificial cornea to which the method for manufacturing an artificial cornea of ​​the present invention can be applied. A first hole (11) is formed in the central portion of the upper mold (10), and a solution (12) for forming an optical portion can be inserted into the first hole (11), and a second hole (13) for injecting a thermosetting solution for forming a support portion can be formed in the peripheral portion of the upper mold (10).

[0124] Figure 11d illustrates a mold for manufacturing an artificial cornea to which the method for manufacturing an artificial cornea of ​​the present invention can be applied. A plurality of lower fitting protrusions (21) for joining with the upper mold (10) can be formed on the lower mold (20).

[0125] Figure 12 shows the manufacturing sequence of an artificial cornea using the mold for manufacturing an artificial cornea of ​​the present invention.

[0126] Figure 13 shows the external appearance of an artificial cornea manufactured according to the present invention.

[0127] Figure 14 shows the detailed structure of an artificial cornea manufactured according to the present invention (A: overall diameter, B: optical diameter, C: apex thickness, D: front radius of curvature, E: back radius of curvature).

[0128] Figure 15 shows the results of confirming the in vitro cell proliferation effect of an artificial cornea manufactured according to the present invention.

[0129] Figure 16 shows the results of confirming the in vivo biocompatibility and cell proliferation effect of an artificial cornea manufactured according to the present invention.

[0130] Figure 17 shows the results of transplanting an artificial cornea manufactured according to the present invention into a rabbit.

[0131] Figure 18 shows the results of transplanting an artificial cornea manufactured according to the present invention into a primate.

[0132]

[0133] Hereinafter, the present invention will be described in more detail through examples. These examples are intended solely to illustrate the present invention, and it will be apparent to those skilled in the art that the scope of the present invention is not limited by these examples.

[0134]

[0135] [Example 1]

[0136] Manufacturing of artificial corneas using photopolymerization and thermal polymerization optics

[0137] <1-1> Manufacturing of artificial cornea

[0138] The purpose of this study was to confirm the photopolymerization conditions during the manufacturing of the optical part of an artificial cornea.

[0139] Specifically, to manufacture the optical part, 2-hydroxyethyl methacrylate and methyl methacrylate were fixed at a weight ratio of 10:1 and dissolved in a mixture of distilled water and methanol to prepare a solution. At this time, 2-hydroxyethyl methacrylate and methyl methacrylate were adjusted to 77 wt% with respect to the total solution. In addition, the weight ratios of distilled water and methanol were adjusted to 85 wt% and 15 wt%, respectively.

[0140] To the above solution, 1.2 wt% of Irgacure 2959 (2-Hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone) and 0.12 wt% of ethylene glycol dimethacrylate (EGDMA) were added relative to the monomer content, and cured for 2 hours under a 365 nm UV lamp at 8 W.

[0141] As a result of inspection with a projector, it was confirmed that when manufactured with 8W, only about 80% to 99% of the optical part was photopolymerized and solidified (polymer), and the remaining 1% to 20% of the optical part existed as a liquid oligomer (Fig. 2a, Fig. 2b).

[0142] As a support manufacturing solution for the optical part manufactured with 8W, a solution was manufactured by dissolving 80 parts by weight of 2-hydroxyethyl methacrylate and 20 parts by weight of methyl methacrylate in a mixture of distilled water and dimethylformamide. At this time, the ratio of the two monomers was adjusted to 25% by weight of the total capacity, and the ratios of distilled water and dimethylformamide as solvents were adjusted to 80 parts by weight and 20 parts by weight, respectively.

[0143] To the above solution, 1.28 wt% of the crosslinking agent pentaerythritol tetraacrylate, 4.6 wt% of the initiator ammonium sulfate, and 2.3 wt% of N,N,N'N' tetramethylethylenediamine were added relative to the monomer, and the polymer was manufactured by thermal polymerization in a 37°C dry oven for 1 hour (Fig. 3).

[0144]

[0145] <1-2> Comparison of manufacturing times for artificial cornea optical components

[0146] We aimed to confirm the change in optical shape according to photopolymerization time.

[0147] When manufacturing an artificial corneal optical part, the change in the shape of the optical part was confirmed by irradiating it for 0 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 10 hours.

[0148] As a result, as shown in [Fig. 4a], it was confirmed that it was in a completely liquid state before photopolymerization. After photopolymerization, solidification began to occur 15 to 30 minutes later. However, when an artificial cornea was manufactured using the photopolymerization results and tested, it was confirmed that the part where polymerization did not occur was washed away during the washing process, and the central thickness of the optical part was less than 0.3 mm, which was different from the human cornea of ​​0.5 mm. If there is a difference from the average human corneal thickness of 0.5 mm, the amount of light refracted by the cornea may change, which may change the amount of light transmitted to the lens.

[0149] After 1 hour, the thickness of the center of all optical parts was 0.486, 0.495, 0.511, 0.502, and 0.522 (mm) for samples 1 to 5, respectively, which was similar to the average thickness of the human body. At this time, the degree of complete polymerization in the center of the optical part in the entire volume of the optical part was about 80%, and the oligomerization was about 20%. At 4 hours, the part that was completely polymerized was about 95-99%, and the oligomerization was about 1-5%. From 6 hours, it was confirmed that the polymerization of all optical parts had progressed to 100%. In addition, it was confirmed that a deformation of the shape occurred due to additional bonding between polymers.

[0150] In addition, after 4 hours, all optical parts were polymerized and additional polymerization was impossible, so it was confirmed that the physical properties of the interface between the optical part and the support part were reduced and the optical part and the support part were separated during the mold extraction process (Fig. 4b).

[0151]

[0152] [Comparative Example 1]

[0153] Manufacturing of artificial cornea using photopolymerization optics

[0154] An artificial cornea was manufactured using only photopolymerization during the manufacturing of the optical part.

[0155] Specifically, to manufacture the optical part, 2-hydroxyethyl methacrylate and methyl methacrylate were fixed at a weight ratio of 10:1 and dissolved in a mixture of distilled water and methanol to prepare a solution. At this time, 2-hydroxyethyl methacrylate and methyl methacrylate were adjusted to 77 wt% with respect to the total solution. In addition, the weight ratios of distilled water and methanol were adjusted to 85 wt% and 15 wt%, respectively.

[0156] To the above solution, 1.2 wt% of Irgacure 2959 (2-Hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone) and 0.12 wt% of ethylene glycol dimethacrylate (EGDMA) were added relative to the monomer content, and cured for 2 hours under a 365 nm UV lamp at 40 W.

[0157] As a support manufacturing solution for the optical part manufactured at 40W, a solution was prepared by dissolving 80 parts by weight of 2-hydroxyethyl methacrylate and 20 parts by weight of methyl methacrylate in a mixture of distilled water and dimethylformamide. At this time, the ratio of the two monomers was adjusted to 25% by weight of the total capacity, and the ratios of distilled water and dimethylformamide as solvents were adjusted to 80 parts by weight and 20 parts by weight, respectively.

[0158] Additionally, it was confirmed that the optical part was 100% polymerized when manufactured at 40W (Fig. 5a).

[0159] To the above solution, 1.28 wt% of the crosslinking agent pentaerythritol tetraacrylate was added relative to the monomer, 4.6 wt% of the initiator ammonium sulfate relative to the monomer, and 2.3 wt% of N,N,N'N' tetramethylethylenediamine relative to the monomer were added, and the polymer was manufactured by thermal polymerization in a dry oven at 37°C for 1 hour (Fig. 5b).

[0160]

[0161] [Comparative Example 2]

[0162] Manufacturing of an artificial cornea by bonding the optical part and the support part using oxygen plasma

[0163] An optical part was manufactured by the method described in Comparative Example 1 (cured for 2 hours under a 40W 365nm UV lamp), and a support part was manufactured by the method described in Example 1 (80 parts by weight of 2-hydroxyethyl methacrylate and 20 parts by weight of methyl methacrylate were dissolved in a mixture of distilled water and dimethylformamide to prepare a solution. At this time, the ratio of the two monomers was adjusted to 25 parts by weight based on the total volume, and the ratios of distilled water and dimethylformamide as solvents were adjusted to 90 parts by weight and 10 parts by weight, respectively. To the solution, 1.28 parts by weight of the crosslinking agent pentaerythritol tetraacrylate was added relative to the monomer, 4.6 parts by weight of the initiator ammonium sulfate was added relative to the monomer, and 2.3 parts by weight of N,N,N'N' tetramethylethylenediamine was added relative to the monomer, and thermally polymerized in a 37℃ dry oven for 1 hour to prepare a polymer.). An artificial cornea was manufactured by treating with oxygen plasma for 20 minutes using the plasma system (Femtoscience, Covance) most commonly used for interfacial bonding (Fig. 6).

[0164]

[0165] [Example 2]

[0166] SEM image of artificial cornea

[0167] The artificial cornea manufactured in the above <Example 1> was freeze-dried and then images were measured using a mini SEM (ISP, IM-60) at 15 KV and 1000x magnification.

[0168] When photopolymerization and thermal polymerization were simultaneously applied to the optical portion, the support portion polymerized like an oligomer on the outside of the optical portion, allowing the support portion to easily penetrate the oligomer. As a result, it was confirmed that the optical portion and support portion took the form of a double network (Figs. 7a and 7b). On the other hand, when the optical portion was manufactured solely by photopolymerization, the support portion solution did not penetrate into the optical portion and polymerization occurred outside, preventing proper bonding between the optical portion and the support portion (Fig. 8).

[0169]

[0170] [Example 3]

[0171] Confirmation of the physical properties of the artificial cornea

[0172] <3-1> Confirmation of physical properties of the optical and support boundary

[0173] The aim was to determine the stress-strain and tensile strength of the optical and support interfaces of artificial corneas manufactured by various methods.

[0174] Specifically, the tensile strength of the optical portion and support portion of Example 1 and Comparative Example 1, and the boundary between the optical portion and support portion of the artificial cornea of ​​Example 1, Comparative Example 1, and Comparative Example 2, was measured using a tensile strength measuring device (Instron 3345). At this time, a 6 (length) x 3 (width) cm sample consisting of the optical portion support portion was used as the tensile strength sample, and the tensile strength measurement speed was fixed at 5 mm / sec.

[0175] As a result, as shown in [Fig. 9] and [Fig. 10a], it was confirmed that the stress-strain and tensile strength of the boundary between the optical part and the support part of the artificial cornea manufactured by the method of [Example 1] was the highest. The maximum tensile strength was about 3 times higher than that of the method using oxygen plasma (Comparative Example 2), which is the most common interface bonding method. In particular, when the artificial cornea was manufactured using high energy of 40 W (Comparative Example 1), it was confirmed that the bonding strength of the boundary between the optical part and the support part was very low, which meant that there was a possibility that the optical part and the support part would be separated due to intraocular pressure after artificial corneal surgery.

[0176] In addition, compared to the boundary between the optical part and the support part of the artificial cornea manufactured by the method of [Example 1] of the present invention (Fig. 10b), it was confirmed that the boundary between the optical part and the support part of Comparative Example 1 had a relatively weak bond with a maximum tensile strength of about 10 KPa (Fig. 10c). Since the average intraocular pressure of the human body is 1.87 KPa, the support part, which is the part in contact with the human body, can exhibit mechanical safety through bonding with the existing tissue even if it has a relatively low value, but the optical part and the boundary between the optical part and the support part, which are not in contact with the human body, can prevent the detachment of the artificial cornea inserted into the human body and prevent mechanical deformation as the physical properties thereof are higher.

[0177]

[0178] <3-2> Confirmation of physical properties of optical part

[0179] After manufacturing five optical parts using the [Example 1] or [Comparative Example 1] method, the maximum tensile strength was measured to confirm whether uniform polymerization was observed.

[0180] As a result, the artificial cornea manufactured by the [Comparative Example 1] method did not form uniform polymerization, and thus the tensile strength had a very large standard deviation (Fig. 10d), whereas the artificial cornea manufactured by the [Example 1] method of the present invention was confirmed to exhibit excellent tensile strength and bonding strength between the optical portion and the support portion through uniform polymerization (Fig. 10e). If the standard deviation of the optical portion properties is large, it may affect the safety of use.

[0181]

[0182] [Example 4]

[0183] Manufacturing of artificial cornea using mold

[0184] The inventors of the present invention applied the method for manufacturing an artificial cornea of ​​Example 1 to a mold for manufacturing an artificial cornea, which they manufactured themselves, to manufacture an artificial cornea.

[0185] Specifically, the aluminum base material was rough-machined with a 5-axis machining machine, and then ultra-precision machined with a 350FG free-form surface machining machine from Nanotech to prepare the upper and lower molds, respectively. At this time, a first hole was formed in the center of the upper mold, and a second hole was formed in the periphery of the upper mold to inject a thermosetting resin composition for forming a support portion. In addition, a UV-transmitting member made of quartz was inserted into the inside of the first hole (Figs. 11a to 11d).

[0186] A solution for forming an optical part was prepared by dissolving 2-hydroxyethyl methacrylate and methyl methacrylate in a fixed 10:1 weight ratio in a mixture of distilled water and methanol, to which 1.2 wt% of Irgacure 2959 (2-Hydroxy-4′-(2-hydroxyethoxy)-2-methylpropiophenone) and 0.12 wt% of ethylene glycol dimethacrylate (EGDMA) were added based on the monomer content. 2 μL of the solution for forming an optical part was dispensed onto the center of the lower mold (quartz) using a 20 μL pipette, and then the upper mold was fastened and cured for 2 hours at room temperature under an 8W 365 nm UV lamp. At this time, the 2-hydroxyethyl methacrylate and methyl methacrylate contents of the total solution were adjusted to 77 wt%. Additionally, the weight ratio of distilled water and methanol was adjusted to 85 parts by weight and 15 parts by weight, respectively.

[0187] Successively, 80 parts by weight of 2-hydroxyethyl methacrylate and 20 parts by weight of methyl methacrylate were dissolved in a mixture of distilled water and dimethylformamide to prepare a support-forming solution. 1.28 parts by weight of pentaerythritol tetraacrylate as a crosslinking agent, 4.6 parts by weight of ammonium sulfate as an initiator, and 2.3 parts by weight of N,N,N'N' tetramethylethylenediamine were added thereto, vortexed for 1 minute, and then 130 μL was inserted into separate molds using a 200 μL pipette and thermally polymerized in a 37°C dry oven for 1 hour to manufacture an artificial cornea in which the optical part and the support part were integrally formed. The ratio of the two monomers was adjusted to 25 parts by weight of the total volume, and the ratios of distilled water and dimethylformamide as solvents were adjusted to 80 parts by weight and 20 parts by weight, respectively.

[0188] Afterwards, the mold in which the artificial cornea was manufactured was hydrated in purified water for 24 hours, and the upper and lower parts of the mold were separated to obtain an artificial cornea (Figs. 12 and 13). The characteristics of the manufactured artificial cornea are as follows (Fig. 14).

[0189] Overall diameter (A)Optical diameter (B)Vertex thickness (C)Radius of curvature (mm)Front (D)Back (E)8 ± 0.5 mm4.5 ± 1 mm0.5 ± 0.1 mm7.8 ± 0.26.5 ± 0.2

[0190]

[0191] [Example 5]

[0192] Confirmation of cell proliferation in manufactured artificial corneas

[0193] The purpose was to confirm the in vitro / in vivo cell proliferation effect of the artificial cornea manufactured by the manufacturing method of the present invention.

[0194] Specifically, human fibroblasts and the artificial cornea of ​​the present invention were co-cultured and observed for 1, 3, and 7 days. In addition, the artificial cornea of ​​the present invention was transplanted subcutaneously into rats, and observed after 3 and 6 weeks by H&E (hematoxylin-eosin stain) staining and M&T (Masson Trichrome stain).

[0195] As a result, it was confirmed that cells penetrated into the scaffold and exhibited excellent biocompatibility and cell proliferation (Fig. 15, Fig. 16).

[0196]

[0197] [Example 6]

[0198] Animal model experiments

[0199] <6-1> Rabbit model

[0200] An artificial cornea manufactured using the manufacturing method of the present invention was transplanted into the eyes of 15 NZW rabbits.

[0201] Specifically, changes in the corneal surface, transplant site, and tissue were observed using Cornea H&E staining in five rabbits at 4, 8, and 12 weeks after artificial cornea transplantation, and fibrosis was observed using Cornea Masson's trichrome staining.

[0202] As a result, it was confirmed that no inflammation was developed, there were no visual disturbances, and the supporting layer and corneal cells successfully fused (Fig. 17).

[0203]

[0204] <6-2> Primate model

[0205] The efficacy was evaluated using the following evaluation indicators for 3 months starting from 4 months after transplantation in cynomolus monkeys.

[0206] No unusual findings were observed in general symptoms or weight changes, and a threat reflex test revealed no differences in response compared to the non-transplanted eye. Furthermore, hematological and blood biochemical tests showed no unusual findings, confirming safety. Histopathological examinations revealed corneal epithelial cell proliferation and fibroblast infiltration in the transplanted eye (Fig. 18).

[0207]

[0208] The present invention can manufacture an artificial cornea in which the optical part and the support part are integrated by stably bonding the interface between the optical part and the support part by manufacturing the optical part for 1 to 4 hours using low-dose UV. The artificial cornea manufactured by the above manufacturing method has a consistent spherical shape, which can increase the success rate of the surgery by making centering easy, and the center of the optical part exhibits uniform and excellent physical properties, which can further increase the physical safety within the human body. In addition, the boundary between the optical part and the support part exhibits excellent physical properties about 100 times that of existing intraocular pressure, which can prevent the early separation of the optical part and the support part due to intraocular pressure within the human body. In addition, the above manufacturing method can improve the appearance of patients who have received an artificial cornea transplant and reduce complications and side effects caused by adhesive materials, so it has industrial applicability.

Claims

1. i) A step of manufacturing an optical part by irradiating a mixture of an acrylic monomer, a photoinitiator, a crosslinking agent, methanol, and distilled water with UV of 5 to 40 W and 300 to 400 nm for 1 to 4 hours and photopolymerizing the mixture; and ii) A step of manufacturing a support part bonded to the optical part by adding a mixture of an acrylic monomer, distilled water, dimethylformamide, a crosslinking agent, a thermal initiator, and N,N,N'N' tetramethylethylenediamine to the manufactured optical part and thermally polymerizing it at 30 to 100°C for 30 minutes to 2 hours; A method for manufacturing an artificial cornea comprising an optical part and a support part.

2. A method for manufacturing an artificial cornea, characterized in that in the first paragraph, the acrylic monomer of step i) is mixed in an amount of 70 to 90 wt%, the photoinitiator is mixed in an amount of 0.1 to 3 wt% based on the monomer, and the crosslinking agent is mixed in an amount of 0.1 to 0.3 wt% based on the monomer.

3. A method for manufacturing an artificial cornea, characterized in that in the first paragraph, the acrylic monomer of step ii) is mixed in an amount of 15 to 35 wt%, the crosslinking agent is mixed in an amount of 1 to 3 wt% based on the monomer, the thermal initiator is mixed in an amount of 3 to 6 wt% based on the monomer, and N,N,N'N' tetramethylethylenediamine is mixed in an amount of 2 to 4 wt% based on the monomer.

4. A method for manufacturing an artificial cornea, characterized in that in the first paragraph, the acrylic monomer is at least one selected from the group consisting of methyl methacrylate, 2-hydroxyethyl methacrylate, trimethylolpropane triacrylate, 1,4-butanediol diacrylate, ethylhexyl acrylate, glycidyl methacrylate, ethyleneglycol dimethacrylate, and 1,6-hexanediol diacrylate.

5. A manufacturing method characterized in that in the first paragraph, the photoinitiator of step i) is at least one selected from the group consisting of 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone, 1-hydroxy-cyclohexyl-phenyl-ketone, and bis(2,4,6-trimethylbenzoyl)-phenylphosphineoxide.

6. A manufacturing method characterized in that in the first paragraph, the crosslinking agent of step i) is at least one selected from the group consisting of pentaerythritol tetraacrylate, pentaerythritol triacrylate, N,N'-methylenebisacrylamide, and ethylene glycol dimethacrylate (EGDMA).

7. A manufacturing method characterized in that in the first paragraph, the distilled water and methanol of step i) are mixed in a weight ratio of 75 to 95:5 to 25.

8. A manufacturing method characterized in that in the first paragraph, only 80 to 99% of the optical part is manufactured by photopolymerization in step i).

9. A manufacturing method characterized in that in the first paragraph, the distilled water and dimethylformamide of step ii) are mixed in a weight ratio of 70 to 90:10 to 30.

10. A manufacturing method characterized in that in the first paragraph, the crosslinking agent of step ii) is at least one selected from the group consisting of pentaerythritol tetraacrylate, pentaerythritol triacrylate, N,N'-methylenebisacrylamide, and ethylene glycol dimethacrylate (EGDMA).

11. A manufacturing method according to claim 1, characterized in that the thermal initiator of step ii) is ammonium persulfate and / or potassium persulfate.

12. Artificial cornea manufactured by the manufacturing method of paragraph 1.

13. An artificial cornea according to claim 12, characterized in that the tensile strength of the interface between the optical portion and the support portion of the artificial cornea is 100 to 200 KPa.

14. An artificial cornea according to claim 12, characterized in that the total diameter of the artificial cornea is 7 to 9 mm, the optical diameter is 3 to 6 mm, and the apex thickness is 0.4 to 0.6 mm.

15. An artificial cornea according to claim 12, characterized in that the radius of curvature of the artificial cornea is 7.5 to 8.0 mm at the front and 6.0 to 7.0 mm at the back. 16.i) A step of manufacturing an optical part by dispensing a mixture of an acrylic monomer, a photoinitiator, a crosslinking agent, methanol, and distilled water into a lower mold, combining the upper mold, and irradiating it with UV of 5 to 40 W and 300 to 400 nm for 1 to 4 hours and photopolymerizing it; and ii) A step of manufacturing a support portion bonded to the optical portion by injecting a mixture of an acrylic monomer, distilled water, dimethylformamide, a crosslinking agent, a thermal initiator, and N,N,N'N' tetramethylethylenediamine into the lower mold in which the optical portion is formed, and then thermally polymerizing the mixture at 30 to 100°C for 30 minutes to 2 hours; A method for manufacturing an artificial cornea comprising an optical part and a support part.

17. A manufacturing method according to claim 16, characterized in that step ii) is performed continuously without separating the upper mold and the lower mold.

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