Intraocular lens material and preparation method thereof

Abstract

The invention provides an artificial lens material and a preparation method thereof. The preparation method comprises the following steps: S1, mixing a (methyl) acrylate monomer and / or a (methyl) acrylamide monomer according to a certain mass ratio to obtain a first mixture; s2, adding a cross-linking agent and an initiator into the first mixture to obtain a first mixed solution; s3, curing the first mixed solution to obtain a first polymer material; s4, performing extraction treatment on the first polymer material to obtain a second polymer material; and S5, immersing the second polymer material into a normal saline solution, and fully hydrating to obtain the artificial lens material. The material has high glass transition temperature while meeting good optical properties such as high refractive index and high Abbe number, can be machined at normal temperature, and has good water absorption, so that the prepared artificial lens is thinner and lower in production cost.

Description

Technical Field

[0001] The present invention relates to the technical field of biomaterials, and in particular to an artificial lens material and a preparation method thereof. Background Art

[0002] Intraocular lens is a medical implant used to replace the transparent lens of the human eye. Its main function is to correct vision. The selection and manufacturing of intraocular lens materials have a crucial impact on its optical properties and biocompatibility. Existing intraocular lens materials mainly include hydrophilic acrylate materials and hydrophobic acrylate materials.

[0003] Hydrophilic acrylate materials are widely used in the manufacture of intraocular lenses due to their good biocompatibility and easy machining properties; however, their low refractive index requires a larger thickness for lenses of the same diopter, increasing the size of the incision required for intraocular lens implantation. Although hydrophobic acrylate materials have a higher refractive index and can produce thinner intraocular lenses, they need to be machined under low-temperature freezing conditions because their glass transition temperature is generally below 10°C, which increases the processing cost and complexity. Patent CN110003385B uses hydrophobic monomers to prepare a foldable intraocular lens material with a high refractive index. Patent CN112292100A uses hydrophobic acrylate monomers with aromatic ring structures or alicyclic structures to copolymerize with hydrophilic acrylate monomers to form acrylic materials with high refractive index and high dispersion coefficient, but the glass transition temperature of such materials is not higher than 15°C. Therefore, it is necessary to develop a polymer material with high refractive index, high Abbe number, and high glass transition temperature to prepare implantable intraocular lenses with lower cost and higher optical performance. Summary of the invention

[0004] In order to solve the problem that the existing hydrophilic acrylate material of the intraocular lens has a low refractive index, while the hydrophobic acrylate material has a low glass transition temperature, the present invention provides a new intraocular lens copolymer material, which has the advantages of both the hydrophilic acrylate material and the hydrophobic acrylate material, that is, it has a high refractive index, a high Abbe number and a high glass transition temperature.

[0005] To achieve the above object, in a first aspect, the present invention provides a method for preparing an artificial lens material, comprising the following steps: S1: mixing a certain mass ratio of (meth)acrylate monomers and / or (meth)acrylamide monomers to obtain a first mixture; S2: adding a cross-linking agent and an initiator to the first mixture to obtain a first mixed solution; S3: solidifying the first mixed solution to obtain a first polymer material; S4: extracting the first polymer material to obtain a second polymer material; S5: Immersing the second polymer material in a physiological saline solution to obtain an artificial lens material after sufficient hydration.

[0006] The beneficial effect of the preparation method of the intraocular lens material provided by the present invention is that: (meth) acrylate is a hydrophobic monomer, (meth) acrylamide is a hydrophilic monomer, and hydrophilic and hydrophobic monomers are selected as main monomers, and a crosslinking agent and an initiator are added to copolymerize them to form a novel intraocular lens material having the advantages of both hydrophilic intraocular lens materials and hydrophobic intraocular lens materials. The material has a high glass transition temperature while meeting good optical properties such as a high refractive index and a high Abbe number, can be machined at room temperature, and has good water absorption. The intraocular lens prepared thereby is thinner and the production cost is also lower.

[0007] In some embodiments, the (meth)acrylate monomer is a (meth)acrylate monomer containing an aromatic ring structure or an alicyclic structure in the substituent; the (meth)acrylamide monomer is a monomer containing as many hydrogen bond donor / acceptor structures as possible. The beneficial effects are: the (meth)acrylate monomer with an aromatic ring structure or an alicyclic structure provides a high refractive index while ensuring a high Abbe number; the (meth)acrylamide monomer with a high hydrogen bond content can provide a high water content and a high glass transition temperature.

[0008] In some embodiments, the (meth)acrylate monomer of the aromatic ring structure includes at least one of benzyl (meth)acrylate, 2-phenylethyl (meth)acrylate, 2-phenoxyethyl (meth)acrylate, and 4-phenylbutyl (meth)acrylate; The alicyclic (meth)acrylate monomer comprises at least one of cyclohexyl (meth)acrylate, 2-cyclohexylethyl (meth)acrylate and ethylene glycol dicyclopentenyl ether acrylate; The (meth)acrylamide monomer includes at least one of ethylene glycol dicyclopentenyl ether acrylate, (meth)acrylamide, N-methylacrylamide, N-n-butylacrylamide, N,N-dimethylacrylamide and hydroxyethylacrylamide.

[0009] In some embodiments, the crosslinking agent includes at least one of ethylene glycol dimethacrylate, ethylene glycol di(meth)acrylate, diethylene glycol di(meth)acrylate, triethylene glycol di(meth)acrylate, 1,6-hexanediol di(meth)acrylate, 1,4-butanediol di(meth)acrylate, N,N′-methylenebisacrylamide, and N,N′-hexamethylenebis(methacrylamide).

[0010] In some embodiments, the initiator includes a thermal initiator and a photoinitiator; The thermal initiator comprises at least one of 2,2'-azobisisobutyronitrile, 2,2'-azobisisovaleronitrile, 2,2'-azobisisoheptanenitrile, dibenzoyl peroxide, and bis-(4-tert-butylcyclohexyl) peroxydicarbonate; The photoinitiator comprises at least one of phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide, 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylpropiophenone, diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide and phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide.

[0011] In some embodiments, before S3, the method includes: The first mixed solution is bubbled with nitrogen for more than 3 minutes. The beneficial effect is that the nitrogen can remove dissolved oxygen in the first mixed solution and reduce the influence of oxygen on the polymerization process.

[0012] In some embodiments, the S3 includes: introducing the first mixed solution into a mold and sealing it; The mold is illuminated and / or heated to solidify the first mixed solution to obtain the first polymer material. The beneficial effect is that the illumination and / or heating causes the components in the first mixed solution to undergo a polymerization reaction and solidify to form a high molecular copolymer material, which serves as a blank for subsequent product processing.

[0013] In some embodiments, before S4, the method includes: The first polymer material is processed in shape.

[0014] In some embodiments, the extractant is an organic solvent that can properly swell the material. The beneficial effect is that the organic solvent can extract and remove uncured residual monomers and other small molecules to reduce the overall leachable content in the material and reduce the potential clinical risks of product application.

[0015] In a second aspect, an embodiment of the present invention provides an artificial lens material prepared by the above-mentioned preparation method.

[0016] The beneficial effects of the present invention are that the prepared artificial lens material has the advantages of both hydrophilic artificial lens material and hydrophobic artificial lens material. The material has a high glass transition temperature while meeting good optical properties such as high refractive index and high Abbe number. The prepared artificial lens is thinner and the production cost is lower. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1The present invention is a flowchart of a method for preparing an intraocular lens material according to an embodiment of the present invention. DETAILED DESCRIPTION

[0018] In order to make the purpose, technical scheme and advantages of the present invention clearer, the technical scheme in the embodiment of the present invention will be described clearly and completely in conjunction with the accompanying drawings of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in the field without creative work belong to the scope of protection of the present invention. Unless otherwise defined, the technical terms or scientific terms used herein should be the common meanings understood by people with ordinary skills in the field to which the present invention belongs. "Including" and similar words used in this article mean that the elements or objects appearing before the word include the elements or objects listed after the word and their equivalents, without excluding other elements or objects. Unless otherwise specified, the "connection" described in this article can be a direct connection or an indirect connection, that is, a connection through an intermediate. The "(meth)" described in this article means that the monomer may contain a methyl group or may not contain a methyl group, such as "(meth) acrylate" means both methacrylate and acrylate.

[0019] In view of the problems existing in the prior art, an embodiment of the present invention provides a method for preparing an artificial lens material, comprising the following steps: S1: mixing a certain mass ratio of (meth)acrylate monomers and / or (meth)acrylamide monomers to obtain a first mixture; S2: adding a cross-linking agent and an initiator to the first mixture to obtain a first mixed solution; S3: curing the first mixed solution to obtain a first polymer material; S4: extracting the first polymer material to obtain a second polymer material; S5: immersing the second polymer material in a physiological saline solution and obtaining an artificial lens material after sufficient hydration.

[0020] In this embodiment, the mass ratio of the (meth)acrylate monomer and / or (meth)acrylamide monomer is not specifically limited and can be selected according to actual conditions. The order of S1 and S2 is not limited. The crosslinking agent and the initiator can be mixed first to obtain the first mixture, and then a certain mass ratio of (meth)acrylate monomer and / or (meth)acrylamide monomer is added to obtain the first mixed solution. In addition, when the second polymer material is immersed in a physiological saline solution for hydration, water molecules will enter the material to swell the material. When the total mass of the material reaches a constant, it means that the swelling equilibrium state has been reached and the hydration is sufficient.

[0021] In some embodiments, the (meth)acrylate monomer is a (meth)acrylate monomer containing an aromatic ring structure or an alicyclic ring structure in a substituent; and the (meth)acrylamide monomer is a monomer containing a hydrogen bond donor / acceptor structure.

[0022] In this embodiment, methyl-containing acrylate monomers may be preferentially selected. Furthermore, (meth)acrylate monomers containing aromatic ring structures or alicyclic structures in the substituents may provide a high refractive index, while monomers containing dicyclopentenyl structures may provide a high refractive index while ensuring a high Abbe number. (Meth)acrylamide monomers with a high hydrogen bond content may provide a high glass transition temperature and a high water content, so that they can be processed and formed at room temperature, and at the same time make the hydrated intraocular lens softer.

[0023] In some embodiments, the (meth)acrylate monomer with an aromatic ring structure includes at least one of benzyl (meth)acrylate, 2-phenylethyl (meth)acrylate, 2-phenoxyethyl (meth)acrylate, and 4-phenylbutyl (meth)acrylate; the (meth)acrylate monomer with an alicyclic structure includes at least one of cyclohexyl (meth)acrylate, 2-cyclohexylethyl (meth)acrylate, and ethylene glycol dicyclopentenyl ether acrylate; the (meth)acrylamide monomer includes at least one of (meth)acrylamide, N-methylacrylamide, N-n-butylacrylamide, ethylene glycol dicyclopentenyl ether acrylate, N,N-dimethylacrylamide, and hydroxyethyl acrylamide.

[0024] In some specific embodiments, N,N-dimethylacrylamide and hydroxyethylacrylamide are selected as hydrophilic monomers, ethylene glycol dicyclopentenyl ether acrylate is selected as a hydrophobic monomer, and the three main monomers are copolymerized to prepare an intraocular lens material.

[0025] In some embodiments, the crosslinking agent includes at least one of ethylene glycol dimethacrylate, ethylene glycol di(meth)acrylate, diethylene glycol di(meth)acrylate, triethylene glycol di(meth)acrylate, 1,6-hexanediol di(meth)acrylate, 1,4-butanediol di(meth)acrylate, N,N′-methylenebisacrylamide, and N,N′-hexamethylenebis(methacrylamide).

[0026] In some embodiments, the initiator includes a thermal initiator and a photoinitiator; the thermal initiator includes: at least one of 2,2'-azobisisobutyronitrile, 2,2'-azobisisovaleronitrile, 2,2'-azobisisoheptanoonitrile, dibenzoyl peroxide, and bis-(4-tert-butylcyclohexyl) peroxydicarbonate; the photoinitiator includes: at least one of phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide, 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone, diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide, and phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide.

[0027] In this embodiment, a thermal initiator and a photoinitiator may be selected according to needs, and one or more types may be selected.

[0028] In some specific embodiments, ethylene glycol dimethacrylate is selected as the crosslinking agent, and phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide is selected as the photoinitiator.

[0029] In some embodiments, before S3, the step includes: bubbling nitrogen into the first mixed solution, and the time for bubbling nitrogen is more than 3 minutes.

[0030] In some embodiments, S3 includes: introducing the first mixed solution into a mold and sealing it; and irradiating the mold with light and / or heating to solidify the first mixed solution to obtain the first polymer material.

[0031] In this embodiment, the mold may be made of polypropylene, and the mold may fix the first solution into a specific shape. After irradiating and / or heating the mold, the first mixed solution may be solidified to form a solid for easy processing. When the first mixed solution is cured by irradiation, the wavelength range of light initiation may be set to 365nm~405nm, and when the first mixed solution is cured by heating, the heating temperature range may be set to 40℃~100℃.

[0032] In some embodiments, before S4, the step includes: processing the shape of the first polymer material.

[0033] In this embodiment, the outer shape of the first polymer material can be processed at room temperature, such as by turning, milling and other processes to produce the optical surface, shape structure and other features of the product.

[0034] In some embodiments, the extractant is an organic solvent.

[0035] In this embodiment, the organic solvent may be acetonitrile, ethanol, acetone or other organic solvents. The first polymer is immersed in the organic solvent, or the organic solvent is extracted by Soxhlet extraction, and the organic solvent can extract and remove the residual monomers on the first polymer material. After the extraction is completed, the material is dried at 60° C. to remove the solvent components, and then immersed in a physiological saline solution for hydration.

[0036] A second aspect of the present invention provides an artificial lens material, which is prepared by the above-mentioned preparation method.

[0037] The present invention is further described below by specific examples. Unless otherwise specified, the reagents, materials and instruments used below are all conventional reagents, conventional materials and conventional instruments, which can be obtained commercially, and the reagents and materials involved can also be synthesized by conventional synthesis methods.

[0038] Example 1 1) mixing ethylene glycol dicyclopentenyl ether acrylate (EGDCA): N,N-dimethylacrylamide (DMAA): hydroxyethylacrylamide (HEAA) in a ratio of 70:15:15 by mass to obtain a first mixture, and mixing ethylene glycol dimethacrylate (EGDMA): phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide (photoinitiator 819) in a ratio of 1:0.5 by mass to obtain the first mixture, and shaking to fully dissolve the components to obtain a first mixed solution; 2) introducing nitrogen into the first mixed solution, bubbling with nitrogen for 5 minutes, and then introducing the solution into a polypropylene mold and sealing the mold; 3) Using an LED light with a wavelength of 405 nm to irradiate the mold to solidify the first mixed solution to obtain the first polymer material.

[0039] 4) Testing the refractive index RI, Abbe number, equilibrium water content EWC and glass transition temperature Tg of the first polymer material.

[0040] Testing items and methods: Refractive index RI: Soak the test material in physiological saline solution for 30 hours, then take it out and wipe off the surface moisture. Place it on the test table of ATAGO DR-M2 Abbe refractometer, and measure the refractive index of the material at 25°C and 546nm wavelength.

[0041] Abbe number: At 25°C, use ATAGO DR-M2 Abbe refractometer to measure the material at 89nm (n D )、486nm(n F ) and 656nm (n C ) Refractive index at three different wavelengths. Calculate the Abbe number of the material: .

[0042] Equilibrium water content EWC: First, dry the test material in a 60℃ forced air drying oven to constant weight, and measure the dry weight of the test material; then soak the test material in physiological saline for 32 hours until constant weight, absorb the surface moisture and measure the wet weight of the sample. Then calculate the equilibrium water content of the material EWC = (wet weight - dry weight) / wet weight * 100%.

[0043] Glass transition temperature Tg: The test material was dried in a 60°C forced air drying oven to constant weight. The test sample was then analyzed in a TAQ200 differential scanning calorimeter at a rate of 10 K / min in a nitrogen atmosphere. The glass transition temperature was determined based on the first and second heating scans.

[0044] Embodiment 2-5 The difference between the embodiment 1 and the embodiment 1 is that the mass percentages of ethylene glycol dicyclopentenyl ether acrylate, N,N-dimethylacrylamide and hydroxyethylacrylamide added are different.

[0045] Embodiment 6-7 The difference between this embodiment and embodiment 1 is that the mass ratio of the added ethylene glycol dimethacrylate is different.

[0046] The specific proportions of Example 1, Example 2, Example 3, Example 4 and Example 5 can be seen in Table 1.

[0047] Table 1

[0048] The test results of Example 1, Example 2, Example 3, Example 4 and Example 5 are shown in Table 2.

[0049] Table 2

[0050] According to the test results in Examples 1 to 5, it can be analyzed that the use of two acrylamide monomers, DMAA+HEAA, to replace the traditional HEMA as a hydrophilic monomer can provide an equivalent water content with less hydrophilic monomer content, increase the amount of other monomers that can be added in the formula, and thus improve the refractive index of the material. At the same time, by using EGDCA as the main monomer of the formula to replace the traditional aromatic acrylate monomer, a high Abbe number can be guaranteed while providing a higher refractive index, so that the Abbe number of the polymer material after hydration is close to the Abbe number of pure water, and will not change significantly with the change of water content. For Example 2, the material is obviously turbid and white after hydration, and it cannot be tested, indicating that the HEAA and EGDCA components have phase separation during the curing process, resulting in a significant difference in water content between the separated phases after hydration; in the remaining embodiments, the DMAA content is guaranteed to be not less than HEAA, and DMAA can play a role similar to a co-solvent, and phase separation will not occur.

[0051] The specific ratios of Example 1, Example 6 and Example 7 can be seen in Table 3.

[0052] Table 3

[0053] The test results of Example 1, Example 6 and Example 7 are shown in Table 4.

[0054] Table 4

[0055] According to the test results in Example 1 and Examples 6-7, it can be analyzed that adjusting the content of the crosslinking agent EGDMA in the formula has little effect on the optical properties of the material.

[0056] Based on the above test results, it can be analyzed that a series of polymer materials can be obtained by copolymerizing the three monomers EGDCA, DMAA, and HEAA with the crosslinker EGDMA under the action of photoinitiator 819. Their glass transition temperatures are all above 40°C, so they are all in a glassy state at room temperature and can be generally machined. At the same time, by adjusting the ratio of monomers to crosslinkers in the composition, the water content of the polymer material after hydration can be changed, thereby affecting its mechanical properties to meet the needs of different product functional designs.

[0057] The above is only a specific implementation of the embodiment of the present application, but the protection scope of the embodiment of the present application is not limited thereto, and any changes or replacements within the technical scope disclosed in the embodiment of the present application should be included in the protection scope of the embodiment of the present application. Therefore, the protection scope of the embodiment of the present application should be based on the protection scope of the claims.

Claims

1. A method for preparing an artificial lens material, characterized in that: The following steps are involved: S1: mixing a certain mass ratio of (meth)acrylate monomers and / or (meth)acrylamide monomers to obtain a first mixture; S2: adding a cross-linking agent and an initiator to the first mixture to obtain a first mixed solution; S3: solidifying the first mixed solution to obtain a first polymer material; S4: extracting the first polymer material to obtain a second polymer material; S5: Immersing the second polymer material in a physiological saline solution to obtain an artificial lens material after sufficient hydration.

2. The method for preparing an intraocular lens material according to claim 1, characterized in that: The (meth)acrylate monomer is a (meth)acrylate monomer containing an aromatic ring structure or an alicyclic ring structure in the substituent; The (meth)acrylamide monomer is a monomer containing a hydrogen bond donor / acceptor structure.

3. The method for preparing an intraocular lens material according to claim 2, characterized in that: The (meth)acrylate monomer of the aromatic ring structure comprises at least one of benzyl (meth)acrylate, 2-phenylethyl (meth)acrylate, 2-phenoxyethyl (meth)acrylate and 4-phenylbutyl (meth)acrylate; The alicyclic (meth)acrylate monomer comprises at least one of cyclohexyl (meth)acrylate, 2-cyclohexylethyl (meth)acrylate and ethylene glycol dicyclopentenyl ether acrylate; The (meth)acrylamide monomer includes at least one of (meth)acrylamide, N-methylacrylamide, N-n-butylacrylamide, ethylene glycol dicyclopentenyl ether acrylate, N,N-dimethylacrylamide and hydroxyethylacrylamide.

4. The method for preparing an intraocular lens material according to claim 1, characterized in that: The crosslinking agent includes at least one of ethylene glycol dimethacrylate, ethylene glycol di(meth)acrylate, diethylene glycol di(meth)acrylate, triethylene glycol di(meth)acrylate, 1,6-hexanediol di(meth)acrylate, 1,4-butanediol di(meth)acrylate, N,N′-methylenebisacrylamide, and N,N′-hexamethylenebis(methacrylamide).

5. The method for preparing an intraocular lens material according to claim 1, characterized in that: The initiator includes a thermal initiator and a photoinitiator; The thermal initiator comprises at least one of 2,2'-azobisisobutyronitrile, 2,2'-azobisisovaleronitrile, 2,2'-azobisisoheptanenitrile, dibenzoyl peroxide, and bis-(4-tert-butylcyclohexyl) peroxydicarbonate; The photoinitiator comprises at least one of phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide, 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylpropiophenone, diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide and phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide.

6. The method for preparing an artificial lens material according to claim 1, characterized in that: Before the S3 includes: Nitrogen gas is bubbled into the first mixed solution, and the time for bubbling nitrogen gas is more than 3 minutes.

7. The method for preparing an artificial lens material according to claim 6, characterized in that: The S3 includes: introducing the first mixed solution into a mold and sealing it; The mold is illuminated and / or heated to solidify the first mixed solution to obtain the first polymer material.

8. The method for preparing an artificial lens material according to claim 1, characterized in that: Before said S4 includes: The first polymer material is processed in shape.

9. The method for preparing an artificial lens material according to claim 8, characterized in that: The extractant is an organic solvent.

10. An artificial lens material, characterized in that: The method is prepared by the method according to any one of claims 1 to 9.

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