Polymer material based on modified collagen as well as preparation method and application of polymer material

Abstract

The invention discloses a polymer material based on modified collagen as well as a preparation method and application thereof, the polymer material comprises a grafted and copolymerized biocompatible material and an acrylic monomer, and the biocompatible material comprises one or a combination of the modified collagen and modified collagen peptide. The polymer material provided by the invention can realize 1.0% of collagen copolymerization amount, ensures the biocompatibility and performance of the product, and can be used as an implantable eye endoscope material; the polymer material can be obtained through polymerization under conventional initiation conditions, the cost is reduced, and the polymer material has high universality and market prospects; when the polymer material is used as an implantable eye endoscope material, the adsorption of an eye endoscope to intraocular protein can be reduced, and the possibility of problems such as infection or xerophthalmia in the eyes of a patient is effectively reduced.

Description

Technical Field

[0001] This application belongs to the technical field of implantable intraocular lenses, and specifically relates to a polymer material based on modified collagen, its preparation method and application. Background Art

[0002] Conventional myopia correction surgeries have the disadvantages of being unable to correct ultra-high myopia and being irreversible. In contrast, ICL (implantable collamer lens) has many advantages, such as not cutting corneal tissue, having a wider correction range, being implantable in the eye for a long time, and being removable or replaceable at any time. Since the first successful ICL implantation in 1997, with the improvement of technology and the in-depth clinical research, ICL has become a safe, effective and popular technical option.

[0003] The star product among existing ICL materials is the Collamer material of Swiss STAAR Company. This material adds an extract of porcine eye collagen, and its core is a copolymer of collagen and acrylic monomers. According to STAAR Company's patent US005993796A, its preparation process is to first extract porcine eye sclera collagen with formic acid, then mix the obtained extract with HEMA and the ultraviolet absorber MHBPH, and finally obtain an ICL material with good biocompatibility and capable of filtering most ultraviolet light through gamma-ray initiation. However, this method requires gamma rays for polymerization. Gamma-ray sources are expensive and difficult to obtain, and the operation threshold is high, which is not conducive to mass production and research. In addition, if collagen and acrylic monomers are directly copolymerized, the copolymerization amount of collagen will be insufficient, thus affecting the biocompatibility of the ICL material and resulting in insufficient product performance.

[0004] There are also corresponding domestic studies on ICL materials. For example, patent CN118165170A provides a preparation method of an implantable intraocular lens based on dopamine. This method polymerizes dopamine with monomers such as HEMA, HEA, and GLMA to prepare an implantable intraocular lens material with good mechanical properties and capable of absorbing blue light. However, dopamine copolymerization is achieved through non-covalent binding, and its degradation resistance in the intraocular environment needs further study. Summary of the Invention

[0005] The purpose of this application is to provide a polymer material based on modified collagen, its preparation method and application, so as to solve the technical problems in the prior art that the copolymerization of collagen and acrylic monomers requires gamma rays, which are expensive and difficult to obtain, with a high operation threshold and not conducive to mass production and research. Direct copolymerization will result in insufficient copolymerization amount of collagen, affecting the biocompatibility of the ICL material and resulting in insufficient product performance.

[0006] To achieve the above object, a first aspect of the present application provides a polymer material based on modified collagen, comprising a graft copolymerized biocompatible material and an acrylic monomer, wherein the biocompatible material comprises one or a combination of two of modified collagen and modified collagen peptide, and the modified collagen and modified collagen peptide are grafted with a reactive monomer, and the reactive monomer is selected from one or a combination of more of (meth)acrylic anhydride, itaconic anhydride, maleic anhydride, allyl glycidyl ether, (meth)acrylic glycidyl ester.

[0007] In one or more embodiments, the biocompatible material is modified collagen, and the mass fraction of modified collagen in the polymer material is 0.01 - 1.0 wt%.

[0008] In one or more embodiments, the biocompatible material is modified collagen peptide, and the mass fraction of modified collagen peptide in the polymer material is 0.01 - 5.0 wt%.

[0009] In one or more embodiments, the modified collagen is collagen grafted with the reactive monomer, and the collagen is animal collagen or recombinant collagen having a complete triple helix structure.

[0010] In one or more embodiments, the modified collagen peptide is collagen peptide grafted with the reactive monomer, and the collagen peptide is animal collagen peptide.

[0011] In one or more embodiments, the mass ratio of collagen to the reactive monomer in the modified collagen is 1:(1 - 10).

[0012] In one or more embodiments, the mass ratio of collagen peptide to the reactive monomer in the modified collagen peptide is 1:(1 - 10).

[0013] In one or more embodiments, the acrylic monomer is selected from one or a combination of more of 2-hydroxyethyl methacrylate, 2-hydroxyethyl acrylate, 2-hydroxypropyl methacrylate, 2-hydroxypropyl acrylate, methacrylic acid, acrylic acid, N-(2-hydroxyethyl)methacrylamide, N-(2-hydroxyethyl)acrylamide, (N,N-dimethyl)methacrylamide, N,N-dimethylacrylamide, N-vinylpyrrolidone.

[0014] To achieve the above object, a second aspect of the present application provides a preparation method of the polymer material according to any one of the above embodiments, comprising:

[0015] Modifying collagen and / or collagen peptide to graft it with the reactive monomer to obtain a biocompatible material;

[0016] Disperse the biocompatible material, the acrylic monomer, the initiator, and the crosslinking agent in a solvent and mix them evenly, and then initiate free radical polymerization. After the polymerization reaction is completed, the polymer material is obtained.

[0017] In one or more embodiments, the method for modifying the collagen includes:

[0018] Dissolve the collagen and then dialyze and purify it to obtain a collagen solution;

[0019] Add the reaction monomer to the collagen solution, carry out a grafting reaction in an ice bath with stirring. After the reaction is completed, dialyze to remove the unreacted monomer and the solvent, and then dry to obtain the modified collagen.

[0020] In one or more embodiments, the reaction time of the grafting reaction is 24 to 72 hours.

[0021] In one or more embodiments, the method for modifying the collagen peptide includes:

[0022] Dissolve the collagen peptide, then add a catalyst, dropwise add the reaction monomer, and raise the temperature to carry out a grafting reaction. After the reaction is completed, a reaction solution is obtained;

[0023] Add a precipitating agent to the reaction solution, collect the precipitate, wash and dry it to obtain the modified collagen peptide.

[0024] In one or more embodiments, the catalyst is selected from one or more combinations of sodium hydroxide, triethylamine, and 2-ethyl-4-methylimidazole.

[0025] In one or more embodiments, the precipitating agent is selected from one or more combinations of methanol, ethanol, isopropanol, ether, and petroleum ether, and the volume ratio of the reaction solution to the precipitating agent is 1:(5 - 20).

[0026] In one or more embodiments, the reaction temperature for raising the temperature to carry out the reaction is 30 to 50 °C, and the reaction time is 24 to 72 hours.

[0027] In one or more embodiments, the mass ratio of the biocompatible material, the acrylic monomer, the initiator, and the crosslinking agent is (0.02 - 1.2):100:(0.5 - 1.0):(0.01 - 1.0).

[0028] In one or more embodiments, the initiator is a photoinitiator or a thermal initiator. The photoinitiator is selected from one or more combinations of 2-hydroxy-2-methyl-1-phenyl-1-propanone, 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone, and lithium 1-phenyl-2,4,6-trimethylbenzoylphosphinate. The thermal initiator is selected from one or more combinations of azobisisobutyronitrile, azobisisoheptonitrile, dimethyl 2,2'-azobis(2-methylpropionate), and benzoyl peroxide (BPO).

[0029] In one or more embodiments, the crosslinking agent is selected from one or more combinations of ethylene glycol dimethacrylate, ethylene glycol dimethacrylate, triethylene glycol diacrylate, methylene bisacrylamide, trimethylolpropane triacrylate, and diallyl phthalate.

[0030] To achieve the above object, a third aspect of the present application provides an application of the polymer material based on modified collagen described in any of the above embodiments or the polymer material prepared by the preparation method of any of the above embodiments as an implantable intraocular lens material.

[0031] Different from the prior art, the beneficial effects of the present application are as follows:

[0032] The polymer material based on modified collagen of the present application can achieve a collagen copolymerization amount of 1.0% by polymerizing modified collagen or collagen peptides and acrylic monomers, ensuring the biocompatibility and performance of the product, making it suitable as an implantable intraocular lens material. Moreover, this polymer material can be polymerized under conventional initiation conditions, significantly reducing the preparation cost, and having high popularity and market prospects.

[0033] By modifying collagen and collagen peptides, the present application grafts monomers to react with some amino groups on the protein side chain, reducing the isoelectric point. When used as an implantable intraocular lens material, it can reduce the adsorption of the intraocular lens to intraocular proteins, effectively reducing the possibility of problems such as infection or dry eye in the patient's eye.

[0034] The preparation method of the present application first obtains a biocompatible material through a graft modification method, and then initiates the polymerization of the biocompatible material and acrylic monomers to obtain a polymer material. The entire preparation process has mild reaction conditions and a simple process, and can prepare a polymer material with a collagen copolymerization amount reaching 1%. Under conventional initiation conditions, the copolymerization amount of collagen is ensured, significantly reducing the production cost of ICL materials and having excellent market application prospects. Description of the Drawings

[0035] To more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the following will briefly introduce the drawings required for the description of the embodiments or the prior art. Obviously, the drawings described below are only some embodiments recorded in the present application. For those of ordinary skill in the art, without creative efforts, other drawings can also be obtained based on these drawings.

[0036] Figure 1 It is a schematic flowchart of an embodiment of the preparation method of the polymer material based on modified collagen in the present application;

[0037] Figure 2 It is a schematic flowchart of an embodiment of the modification method of collagen in the present application;

[0038] Figure 3 It is a schematic flowchart of an embodiment of the modification method of collagen peptide in the present application;

[0039] Figure 4 It is a photo of the implantable intraocular lens in Embodiment 1 of the present application;

[0040] Figure 5 It is the circular dichroism spectrum diagram of the modified collagen prepared in Embodiment 1 of the present application;

[0041] Figure 6 It is the SDS-PAGE gel electrophoresis result diagram in Effect Example 1 of the present application;

[0042] Figure 7 It is the transmittance analysis data diagram in Effect Example 2 of the present application;

[0043] Figure 8 It is the protein adsorption amount detection data in Effect Example 3 of the present application. Detailed implementation manners

[0044] In order to enable those skilled in the art to better understand the technical solutions in the present application, the following will clearly and completely describe the technical solutions in the embodiments of the present application in conjunction with the drawings in the embodiments of the present application. Obviously, the described embodiments are only some embodiments of the present application, rather than all embodiments. Based on the embodiments in the present application, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present application.

[0045] In order to simulate the natural tissue microenvironment and improve the clinical performance of materials through functions such as biocompatibility, mechanical support, and cell signal regulation, the materials for implantable collamer lenses (ICLs) generally select natural collagen and copolymers of acrylic monomers. Currently, in the solutions of ICL materials on the market, gamma-ray initiated copolymerization is used to ensure the copolymerization amount of collagen. The gamma-ray source is expensive and difficult to obtain, with a high operation threshold, which is not conducive to mass production and research.

[0046] To solve the above problems, the applicant has developed a new type of ICL material. This ICL material is a polymer material based on modified collagen, which can ensure the copolymerization amount of collagen under conventional initiation conditions, thus significantly reducing the production cost of ICL materials and having excellent market application prospects.

[0047] Specifically, the polymer material based on modified collagen in this application includes graft copolymerized biocompatible materials and acrylic monomers.

[0048] Among them, the biocompatible materials include one or a combination of two of modified collagen and modified collagen peptides. The modified collagen or modified collagen peptide is grafted with a reactive monomer, and the reactive monomer is selected from one or a combination of maleic anhydride, itaconic anhydride, maleic anhydride, allyl glycidyl ether, glycidyl (meth)acrylate, etc.

[0049] In one embodiment, when the biocompatible material is modified collagen, the mass fraction of the biocompatible material can be 0.01 - 1.0 wt%.

[0050] In another embodiment, when the biocompatible material is modified collagen peptide, the mass fraction of the biocompatible material can be 0.01 - 5.0 wt%.

[0051] In one embodiment, the collagen raw material used for the modified collagen in this application is animal collagen or recombinant collagen with a complete triple helix structure. Exemplarily, the source of animal collagen can be bovine bone, cowhide, pigskin, fish skin, etc., and the recombinant collagen can be collagen synthesized by genetic engineering technology.

[0052] In one embodiment, in the modified collagen of this application, the mass ratio of collagen to the reactive monomer is 1:(1 - 10).

[0053] In one embodiment, the collagen peptide raw material used for the modified collagen peptide in this application can be animal collagen peptides, such as fish collagen peptides, chicken collagen peptides, bovine collagen peptides, etc.

[0054] In one embodiment, in the modified collagen peptide of the present application, the mass ratio of the collagen peptide to the reaction monomer can be 1:(1-10).

[0055] In one embodiment, the acrylic monomer is selected from one or a combination of 2-hydroxyethyl methacrylate, hydroxyethyl acrylate, 2-hydroxyethyl methyl acrylate, hydroxyethyl methyl acrylate, acrylic acid, methacrylic acid, N-(2-hydroxyethyl) acrylamide, N-(2-hydroxyethyl) methacrylamide, (N,N-dimethyl) methylacrylamide, N,N-dimethylacrylamide, N-vinylpyrrolidone.

[0056] Based on the polymer materials based on modified collagen in the above embodiments, by using the modified collagen or collagen peptide, the highest copolymerization amount of collagen can reach 1.0%, ensuring the biocompatibility and performance of the product, making it a material for manufacturing implantable intraocular lenses. And this polymer material can be polymerized under conventional initiation conditions, significantly reducing the preparation cost, and having high popularity and market prospects.

[0057] In addition, the isoelectric points of natural collagen and collagen peptide tend to be neutral, being 6-7. Collagen and collagen peptide will adsorb intraocular proteins in the intraocular environment, causing problems such as infection or dry eye. By modifying collagen and collagen peptide, the grafted monomer reacts with some amino groups on the side chain, reducing the isoelectric point, and can reduce the adsorption of intraocular proteins when applied to implantable intraocular lens materials, effectively reducing the possibility of problems such as infection or dry eye in the patient's eye.

[0058] The present application also provides a preparation method of the above polymer material. Please refer to Figure 1 , Figure 1 which is a schematic flow chart of one embodiment of the preparation method of the polymer material based on modified collagen of the present application.

[0059] As Figure 1 shown, this preparation method includes:

[0060] S100. Modify the collagen and / or collagen peptide so that it is grafted with a reaction monomer to obtain a biocompatible material.

[0061] Among them, the purpose of modification is to graft the reaction monomer onto the collagen or collagen peptide.

[0062] In one embodiment, please refer to Figure 2 , Figure 2 which is a schematic flow chart of one embodiment of the modification method of collagen of the present application.

[0063] As Figure 2 shown, the modification method of collagen includes:

[0064] S101a. Dissolve the collagen and then perform dialysis purification to obtain a collagen solution.

[0065] First, in order to remove small molecule impurities in the collagen and retain the target protein, it is necessary to dissolve the collagen and then perform dialysis purification.

[0066] Among them, the solvent can be any solvent that can dissolve collagen, such as acetic acid, etc.

[0067] In one embodiment, the cut-off molecular weight of the dialysis membrane can be 14,000, and dialysis can be performed using a phosphate buffer solution with a pH of 9.0.

[0068] In one embodiment, the dialysis time can be 24 to 72 hours.

[0069] S102a. Add a reaction monomer to the collagen solution, perform grafting reaction in an ice bath with stirring. After the reaction is completed, dialyze to remove unreacted monomers and solvents, and then dry to obtain modified collagen.

[0070] In one embodiment, the grafting reaction time can be 24 to 72 hours.

[0071] In one embodiment, the cut-off molecular weight of the dialysis membrane can be 14,000, and dialysis can be performed using a phosphate buffer solution with a pH of 9.0.

[0072] In one embodiment, drying can specifically be freeze-drying.

[0073] In one embodiment, please refer to Figure 3 , Figure 3 is a schematic flow chart of an embodiment of the modification method of the collagen peptide in the present application.

[0074] As Figure 3 shown, the modification method of the collagen peptide includes:

[0075] S101b. Dissolve the collagen peptide, then add a catalyst, dropwise add a reaction monomer, and raise the temperature to perform a grafting reaction. After the reaction is completed, a reaction solution is obtained.

[0076] Among them, DMSO can be used as the solvent to dissolve the collagen peptide.

[0077] In one embodiment, the catalyst can be selected from one or a combination of sodium hydroxide, triethylamine, 2-ethyl-4-methylimidazole, etc.

[0078] In one embodiment, the reaction temperature for raising the temperature to perform the reaction can be 30 to 50 °C, and the reaction time can be 24 to 72 hours.

[0079] S102b. Add a precipitating agent to the reaction solution, collect the precipitate, wash and dry it to obtain modified collagen peptides.

[0080] In one embodiment, the precipitating agent is selected from one or more combinations of methanol, ethanol, isopropanol, ether, and petroleum ether.

[0081] In one embodiment, the precipitating agent can be selected from one or more combinations of methanol, ethanol, isopropanol, ether, and petroleum ether, and the volume ratio of the reaction solution to the precipitating agent can be 1:(5 - 20).

[0082] In one embodiment, drying can be specifically carried out by freeze-drying.

[0083] S200. Disperse the biocompatible material, acrylic monomer, initiator, and crosslinking agent in a solvent and mix them evenly, and then initiate free radical polymerization. After the polymerization reaction is completed, a polymer material is obtained.

[0084] After the biocompatible material is prepared in the above S100, the biocompatible material and the acrylic monomer can be further copolymerized to obtain a polymer material.

[0085] In one embodiment, the mass ratio of the biocompatible material, acrylic monomer, initiator, and crosslinking agent can be (0.02 - 1.2):100:(0.5 - 1.0):(0.01 - 1.0).

[0086] In one embodiment, the initiator can be a photoinitiator, and the photoinitiator can be selected from one or more combinations of 2-hydroxy-2-methyl-1-phenyl-1-propanone, 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone, and lithium 1-phenyl-2,4,6-trimethylbenzoylphosphinate. Free radical polymerization reaction can be initiated by ultraviolet light to obtain a polymer material.

[0087] In another embodiment, the initiator can be a thermal initiator, and the thermal initiator can be selected from one or more combinations of azobisisobutyronitrile, azobisisoheptonitrile, dimethyl 2,2'-azobis(2-methylpropionate), and benzoyl peroxide. Free radical polymerization reaction can be initiated by heating to obtain a polymer material.

[0088] In one embodiment, the crosslinking agent can be selected from one or more combinations of ethylene glycol dimethacrylate, ethylene glycol dimethacrylate, triethylene glycol diacrylate, methylene bisacrylamide, trimethylolpropane triacrylate, and diallyl phthalate.

[0089] Based on the preparation methods of the above embodiments, first, a biocompatible material is obtained through a graft modification method, and then the biocompatible material and an acrylic monomer are initiated to polymerize to obtain a polymer material. The reaction conditions in the whole preparation process are mild, the process is simple, a polymer material with a collagen copolymerization amount reaching 1% can be prepared, the copolymerization amount of collagen is ensured under conventional initiation conditions, the production cost of the ICL material is significantly reduced, and it has excellent market application prospects.

[0090] The beneficial effects of the technical solutions of this application are further elaborated in detail below with specific examples.

[0091] Example 1:

[0092] An implantable intraocular lens is prepared by the following steps:

[0093] Step 1: Preparation of modified collagen

[0094] Weigh 0.2 g of collagen with a complete triple helix structure, add it to 20 ml of 0.5 M acetic acid solution, place it in an ice bath, and slowly stir to dissolve it evenly. Then add it to a dialysis membrane with a molecular weight cut-off of 14,000 and dialyze it with a phosphate buffer solution with a pH of 9.0 for 24 h; add the dialyzed collagen solution to a round-bottom flask, weigh 1.0 g of methacrylic anhydride, dissolve it evenly with 1 ml of DMSO, and drop it into the collagen solution. Place it in an ice bath and slowly stir and react for 48 h; after the reaction is completed, add the reaction solution to the dialysis membrane and dialyze it with a phosphate buffer solution for three days to remove unreacted monomers and solvents, and then freeze-dry to obtain methacrylic acid graft-modified collagen;

[0095] Step 2: Initiating polymerization

[0096] Weigh 10 mg of modified collagen and dissolve it in 0.5 M acetic acid to prepare a 1% modified collagen solution; weigh 1.8 g of monomer HEMA, 0.2 g of modified collagen solution, 0.01 g of cross-linking agent EGDMA, and 0.01 g of photoinitiator D-1173, and ultrasonicate it at low temperature until it is evenly dispersed to obtain a mixed solution; take 200 μL of the mixed solution and inject it into a mold. The mold is placed in a self-sealing bag, an ice pack is placed, nitrogen is filled for protection, and it is cured under ultraviolet light with a wavelength of 365 nm and an intensity of 50 mW / cm 2 for 60 minutes to obtain an implantable intraocular lens, as Figure 4 shown, Figure 4 is a photo of the implantable intraocular lens of Example 1 of this application.

[0097] As Figure 4 shown, the implantable intraocular lens of Example 1 has good light transmittance and certain strength.

[0098] Examples 2 to 14:

[0099] An implantable intraocular lens, the preparation method is basically the same as that of Example 1, except that:

[0100] When modifying collagen, the types and amounts of grafted monomers are different; the acrylic monomers used to initiate polymerization are different, the addition amount of the modified collagen solution is different, and the types of initiators are different. Please refer to Table 1 below for details.

[0101] Table 1 Preparation parameters of Examples 1 to 14

[0102]

[0103]

[0104] Example 15:

[0105] An implantable intraocular lens is prepared by the following steps:

[0106] Step 1: Preparation of modified collagen peptide

[0107] Weigh 25 g of collagen peptide and 0.1 g of sodium hydroxide, dissolve them in 250 ml of DMSO, add them to a three-necked flask, set the temperature to 50 °C, dropwise add 75 ml of methacrylic anhydride, and react for 24 h; after the reaction is completed, pour the reaction solution into a large beaker, add 1.5 L of methanol, stir for 1 h, precipitate until the solution is clear, and take the precipitate for freeze-drying to obtain the modified collagen peptide grafted with methacrylic acid;

[0108] Step 2: Initiating polymerization

[0109] Weigh 10 mg of modified collagen and dissolve it in 1% modified collagen solution prepared with 0.5 M acetic acid; weigh 1.6 g of monomer HEMA, 0.2 g of MMA, 0.2 g of modified collagen solution, 0.01 g of crosslinking agent EGDMA, and 0.01 g of photoinitiator L-2959, and ultrasonically disperse them evenly at low temperature to obtain a mixed solution; take 200 μL of the mixed solution and inject it into a mold. The mold is placed in a self-sealing bag, an ice bag is placed in it, nitrogen is filled for protection, and it is cured under ultraviolet light with a wavelength of 365 nm and an intensity of 50 mW / cm 2 for 60 minutes to obtain the implantable intraocular lens.

[0110] Examples 16 to 19:

[0111] An implantable intraocular lens, the preparation method is basically the same as that of Example 15, except that:

[0112] When modifying collagen peptides, the grafted monomers, catalysts, and modification reaction temperatures are different; the acrylic monomers for initiating polymerization, the dosages of the modified collagen peptide solutions, the precipitants, the initiators and crosslinking agents, and the methods for initiating polymerization are different. For details, please refer to Table 2 below.

[0113] Table 2 Preparation Parameters of Examples 14 to 18

[0114]

[0115]

[0116] Comparative Example 1:

[0117] An implantable intraocular lens, the preparation method is basically the same as that of Example 1, the difference is that:

[0118] Modified collagen was not added during the initiation of polymerization.

[0119] Effect Example 1: Characterization and Analysis

[0120] Circular dichroism spectroscopy analysis was performed on the modified collagen prepared in Example 1 to determine its protein secondary structure, and Figure 5 , Figure 5 is the circular dichroism spectrum of the modified collagen prepared in Example 1 of this application.

[0121] As Figure 5 shown, the ratio of the positive and negative peak intensities of the modified collagen in Example 1 is 0.14, indicating that the modified collagen in Example 1 has a complete triple helix structure, and the modification does not destroy the complete triple helix structure of collagen.

[0122] Furthermore, SDS-PAGE gel electrophoresis experiments were performed on the modified collagen prepared in Examples 6 to 8. At the same time, a standard protein marker and the unmodified collagen raw materials used in Examples 6 to 8 were introduced as controls, and Figure 6 , Figure 6 is the SDS-PAGE gel electrophoresis result diagram of Effect Example 1 of this application, Figure 6 in which the bands from left to right are: standard protein, unmodified collagen, Example 6, Example 7, and Example 8.

[0123] As Figure 6 shown, it can be seen from the bands that the modified collagen in Examples 6 to 8 has two bands, α and β, at about 100K Da and 130K Da, and the band at about 250K Da is a single-chain dimer, which is the same as the band of the unmodified collagen, further proving that the modified collagen of this application retains the complete triple helix structure.

[0124] Effect Example 2: Transmittance Analysis

[0125] The light transmittance of the intraocular lenses of Examples 1 to 5 and Comparative Example 1 was measured using an ultraviolet spectrophotometer, and Figure 7 , Figure 7 is the light transmittance analysis data graph of Effect Example 2 of the present application.

[0126] As Figure 7 shown, modified collagen was added to the intraocular lenses of Examples 1 to 5 on the basis of Comparative Example 1 during polymerization. The addition of modified collagen would cause a change in the light transmittance of the intraocular lens material. However, the modified collagen in the intraocular lens materials of Examples 1 to 5 could be well combined with the hydrogel, and the transmittance of the intraocular lenses of Examples 1 to 5 remained above 90%, without affecting vision.

[0127] Effect Example 3: Protein adsorption analysis

[0128] A protein adsorption experiment was carried out on the intraocular lens materials of Examples 1, 10 to 13 and Comparative Example 1 to analyze the surface protein adsorption amount. The experimental process was as follows:

[0129] Protein adsorption: First, intraocular lens material samples of the same size (1.38 cm x 1.38 cm) were soaked in PBS standard buffer solution (pH ~ 7.4) for 12 h; then the intraocular lens material samples were immersed in 3 mL of protein solution (PBS solution containing 5 mg / mL of lysozyme and bovine serum albumin) and incubated at 37 °C for 24 h for adsorption;

[0130] Protein elution: After incubation, the samples were gently taken out from the incubation solution and transferred to a centrifuge tube, 3 mL of PBS buffer was added, and the mixture was shaken at 37 °C for 30 min to remove the unadsorbed proteins, and the PBS buffer was replaced once. The above process was repeated; finally, the samples were placed in a centrifuge tube containing 3 mL of 1 wt% SDS solution and shaken at 37 °C for 4 h to elute the proteins adsorbed on their surfaces. The resulting SDS protein solution was the sample to be measured.

[0131] Protein detection: The protein amount of the SDS protein solution was detected using a BCA protein detection kit, and Figure 8 , Figure 8 is the protein adsorption amount detection data of Effect Example 3 of the present application.

[0132] As Figure 8As shown, the intraocular lenses of Examples 1, 10, 11, 12, and 13 gradually reduce the adsorption of bovine serum albumin and gradually increase the adsorption of lysozyme. This indicates that with the increase in the content of modified collagen, the protein adsorption capacity of the intraocular lens gradually weakens. The principle lies in that: the isoelectric point of collagen is biased towards neutral, being 6 - 7. After its modification, the graft monomers react with some amino groups on the side chain, reducing the isoelectric point. Most proteins in the intraocular environment carry negative charges, and modified collagen can reduce the adsorption of intraocular proteins by the intraocular lens material.

[0133] Based on the above various experiments, it can be seen that the implantable intraocular lens material based on modified collagen of the present application can effectively reduce the adsorption of intraocular proteins, can provide necessary optical transparency, and collagen is the main component of the cornea and sclera, having good biocompatibility with eye tissues. It is a very promising implantable intraocular lens material.

[0134] For those skilled in the art, it is obvious that the present application is not limited to the details of the above exemplary embodiments, and without departing from the spirit or basic characteristics of the present application, the present application can be implemented in other specific forms. Therefore, from any perspective, the embodiments should be regarded as exemplary and non - restrictive. The scope of the present application is defined by the appended claims rather than the above description. Therefore, all changes falling within the meaning and scope of the equivalent elements of the claims are intended to be encompassed within the present application. Any reference signs in the claims should not be regarded as limiting the claimed rights.

[0135] In addition, it should be understood that although this specification is described according to embodiments, not every embodiment only contains an independent technical solution. This narrative way of the specification is only for clarity. Those skilled in the art should regard the specification as a whole, and the technical solutions in each embodiment can also be appropriately combined to form other embodiments that can be understood by those skilled in the art.

Claims

1. A polymer material based on modified collagen, characterized in that: It comprises a graft copolymerized biocompatible material and an acrylic monomer, wherein the biocompatible material comprises one or a combination of modified collagen and modified collagen peptides, the modified collagen and modified collagen peptides are grafted with reactive monomers, and the reactive monomers are selected from one or more combinations of (meth)acrylic anhydride, itaconic anhydride, maleic anhydride, allyl glycidyl ester, and (meth) glycidyl acrylate.

2. The polymer material according to claim 1, characterized in that The biocompatible material is modified collagen, and the mass fraction of the modified collagen in the polymer material is 0.01-1.0wt%; or, The biocompatible material is modified collagen peptide, and the mass fraction of the modified collagen peptide in the polymer material is 0.01-5.0wt%.

3. The polymer material according to claim 1, characterized in that The modified collagen is collagen grafted with the reactive monomer, and the collagen is animal collagen or recombinant collagen with a complete triple helix structure; and / or, The modified collagen peptide is a collagen peptide grafted with the reactive monomer, and the collagen peptide is an animal collagen peptide.

4. The polymer material according to claim 1, characterized in that The mass ratio of the collagen in the modified collagen to the reactive monomer is 1:(1-10).

5. The polymer material according to claim 1, characterized in that The mass ratio of the collagen peptide in the modified collagen peptide to the reactive monomer is 1:(1-10).

6. The polymer material according to claim 1, characterized in that The acrylic monomer is selected from one or more combinations of hydroxyethyl methacrylate, hydroxyethyl acrylate, hydroxymethyl methacrylate, hydroxymethyl acrylate, acrylic acid, methacrylic acid, N-(2-hydroxyethyl)acrylamide, N-(2-hydroxyethyl)methacrylamide, (N,N-dimethyl)methacrylamide, N,N-dimethylacrylamide, and N-vinyl pyrrolidone.

7. A method for preparing a polymer material according to any one of claims 1 to 6, characterized in that: include: Modifying collagen and / or collagen peptide so that the reactive monomer is grafted thereon to obtain a biocompatible material; The biocompatible material, the acrylic monomer, the initiator, and the cross-linking agent are dispersed in a solvent and mixed evenly, and then free radical polymerization is initiated. After the polymerization reaction is completed, the polymer material is obtained.

8. The preparation method according to claim 7, characterized in that: The collagen modification method comprises: Dissolving collagen and dialysis purification to obtain a collagen solution; Adding the reactive monomer to the collagen solution, ice bathing and stirring to carry out grafting reaction, after the reaction is completed, dialyzing to remove unreacted monomer and solvent, and then drying to obtain modified collagen; Preferably, the reaction time of the grafting reaction is 24 to 72 hours.

9. The preparation method according to claim 7, characterized in that: The modification method of the collagen peptide comprises: Dissolve the collagen peptide, then add a catalyst, dropwise add the reaction monomer, raise the temperature to carry out the grafting reaction, and after the reaction is completed, obtain a reaction solution; A precipitant is added to the reaction solution, and the precipitate is collected, washed, and dried to obtain a modified collagen peptide.

10. The preparation method according to claim 9, characterized in that: The catalyst is selected from one or more combinations of sodium hydroxide, triethylamine, and 2-ethyl-4-methylimidazole, and the mass ratio of the catalyst to the collagen peptide is (0.1-1):25; and / or, The precipitant is selected from one or more combinations of methanol, ethanol, isopropanol, ether and petroleum ether, and the volume ratio of the reaction solution to the precipitant is 1:(5-20); and / or, The reaction temperature for the heating reaction is 30 to 50° C., and the reaction time is 24 to 72 hours.

11. The preparation method according to claim 7, characterized in that: The mass ratio of the biocompatible material, acrylic monomer, initiator and cross-linking agent is (0.02-1.2):100:(0.5-1.0):(0.01-1.0).

12. The preparation method according to claim 7, characterized in that: The initiator is a photoinitiator or a thermal initiator, wherein the photoinitiator is selected from one or more combinations of 2-hydroxy-2-methyl-1-phenyl-1-propanone, 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone, and 1-phenyl-2,4,6-trimethylbenzoyl lithium phosphite, and the thermal initiator is selected from one or more combinations of azobisisobutyronitrile, azobisisoheptanenitrile, dimethyl azobisisobutyrate, and dibenzoyl peroxide BPO; and / or, The crosslinking agent is selected from one or more combinations of ethylene glycol dimethacrylate, ethylene glycol dimethacrylate, triethylene glycol diacrylate, methylene bisacrylamide, trimethylolpropane triacrylate and dipropylene phthalate.

13. Use of the modified collagen-based polymer material according to any one of claims 1 to 6 or the polymer material prepared by the preparation method according to any one of claims 7 to 12 as an implantable intraocular lens material.

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