Artificial corneal endothelium sheet as well as preparation method and application thereof

Abstract

The invention relates to an artificial corneal endothelium sheet as well as a preparation method and application thereof. The artificial corneal endothelium sheet is prepared from the following raw materials: a hydrophilic monomer, a hydrophobic monomer, a cross-linking agent, an ultraviolet absorption monomer, a blue light absorption monomer and an initiator, the hydrophilic monomer comprises a combination of hydroxyethyl methylacrylate and polyethylene glycol methacrylate, and the hydrophobic monomer comprises a combination of methyl methacrylate and isobutyl methacrylate; in the preparation raw materials, the use amount of the hydrophilic monomer is 80-94 wt%, and the use amount of the hydrophobic monomer is 5-19 wt%. According to the artificial corneal endothelium sheet provided by the invention, the proportion and components of the hydrophilic monomer and the hydrophobic monomer are regulated and controlled, so that the obtained artificial corneal endothelium sheet is moderate in water content and has excellent mechanical properties, adhesion performance and swelling stability.

Description

Technical Field

[0001] This invention relates to the field of medical materials technology, and in particular to an artificial corneal endothelial graft, its preparation method, and its application. Background Technology

[0002] Bullous keratopathy is a common blinding eye disease caused by damage to corneal endothelial cells. Adult corneal endothelial cells have limited proliferative capacity; once their function is impaired due to intraocular surgery, infection, or genetic diseases, subepithelial bullae, corneal edema and opacity, and eye pain may occur, potentially leading to blindness in severe cases. Currently, there is no specific treatment; in advanced stages, only high-quality donor corneal transplantation can be effective. However, factors such as donor scarcity, repeated insufflation, immune rejection, and abnormally low corneal endothelial cell density significantly increase the risk of transplant failure. Furthermore, some patients with specific conditions cannot benefit from conventional transplantation, making it a challenging clinical problem.

[0003] Artificial corneal endothelial grafts have emerged as a novel treatment method. However, current clinically used artificial corneal endothelial grafts suffer from problems such as poor graft adhesion, insufficient biocompatibility, and residual monomer toxicity, which severely restrict their clinical translation and promotion. Therefore, providing an artificial corneal endothelial graft material with moderate water content, excellent mechanical properties, adhesion performance, swelling stability, and low toxicity has great application prospects. Summary of the Invention

[0004] To address the aforementioned technical problems, this invention provides an artificial corneal endothelial patch, its preparation method, and its applications. The artificial corneal endothelial patch provided by this invention, by adjusting the ratio and composition of hydrophilic and hydrophobic monomers, achieves an artificial corneal endothelial patch with moderate water content, exhibiting excellent mechanical properties, adhesion properties, and swelling stability.

[0005] To achieve this objective, the present invention adopts the following technical solution:

[0006] In a first aspect, the present invention provides an artificial corneal endothelial patch, wherein the raw materials for preparing the artificial corneal endothelial patch include: hydrophilic monomers, hydrophobic monomers, crosslinking agents, ultraviolet absorbing monomers, blue light absorbing monomers, and initiators;

[0007] The hydrophilic monomer includes a combination of hydroxyethyl methacrylate and polyethylene glycol methacrylate, and the hydrophobic monomer includes a combination of methyl methacrylate and isobutyl methacrylate.

[0008] The content of hydrophilic monomers in the raw materials is 80-94 wt% (e.g., 80 wt%, 82 wt%, 85 wt%, 88 wt%, 90 wt%, 94 wt%, etc.), and the content of hydrophobic monomers is 5-19 wt% (e.g., 5 wt%, 8 wt%, 10 wt%, 12 wt%, 15 wt%, 18 wt%, 19 wt%, etc.).

[0009] In this invention, the amounts of hydrophilic and hydrophobic monomers affect the water content, mechanical properties, adhesion properties, and swelling stability of the resulting artificial corneal endothelial graft. If the proportion of hydrophobic segments in the polymer network is too high, the network structure will be too dense, resulting in excessive material rigidity. This makes it difficult for the material to form a tight, conformal adhesion to the soft corneal stroma layer within the eye through natural surface tension and slight negative pressure, easily creating tiny gaps and increasing the risk of postoperative interstitial fluid accumulation. Regarding biocompatibility, dense materials with excessively low water content hinder the penetration and exchange of nutrients such as water and glucose. Simultaneously, overly hydrophobic surfaces are more prone to non-specific protein adsorption, triggering unnecessary inflammatory responses.

[0010] If a material contains too many hydrophilic segments and has an overly loose cross-linking network, it will swell excessively in the aqueous humor and become too soft. This not only prevents it from maintaining its intended macroscopic shape and mechanical support function, but also causes it to shift or detach due to insufficient adhesion strength in the flow of aqueous humor. Regarding biocompatibility, while excessive hydrophilic segments and high water content may allow for unimpeded nutrient transport, the overly loose and porous network structure weakens its crucial barrier function.

[0011] This invention, by controlling the amount of hydrophilic and hydrophobic monomers, achieves an appropriate water content, endowing the material with moderate swelling and ideal viscoelasticity. This allows it to adhere well to the corneal stroma while simultaneously resisting aqueous humor impact with its moderate mechanical strength, ensuring long-term positional stability. At the same time, the appropriate water content balances the contradiction between "permeability" and "barrier": suitable hydrophilic channels are formed internally, enabling the artificial corneal endothelial graft to be waterproof while maintaining a certain degree of permeability to preserve the corneal stroma's nutrient supply and normal metabolism.

[0012] In this invention, the hydrophilic monomers are a combination of hydroxyethyl methacrylate (HEMA) and polyethylene glycol methacrylate (PEGMA). While a single hydrophilic monomer (such as HEMA) can impart basic hydrophilicity to the polymer, the distribution of hydrophilic groups (-OH) on its molecular chain is singular. During polymerization, the aggregation of molecular chains can lead to local enrichment or sparseness of hydrophilic groups, resulting in uneven hydrophilicity on the polymer surface. This invention uses HEMA and polyethylene glycol methacrylate (PEGMA) for hydrophilic composite formation. The two exhibit significant structural complementarity and synergistic effects: structurally, HEMA has a shorter molecular chain and highly active hydrophilic hydroxyl groups, allowing it to quickly form hydrogen bonds with water molecules, ensuring immediate hydrophilicity of the polymer; PEGMA contains long-chain polyethylene glycol segments (… ) nPEGMA exhibits milder hydrophilicity and greater steric hindrance. During polymerization, the long-chain structure of PEGMA effectively inhibits excessive aggregation of HEMA molecular chains, ensuring a uniform distribution of hydrophilic groups (-OH, -O-) on the polymer molecular chains. This avoids excessive polymer swelling due to localized excessive hydrophilicity or decreased application suitability due to localized insufficient hydrophilicity. From a molecular interaction perspective, the hydrophilic groups of HEMA and PEGMA can form intramolecular and intermolecular hydrogen bonds, enhancing the structural stability of the hydrophilic regions. Compared to single HEMA or PEGMA systems, the composite hydrophilic system has a more uniform and robust hydrophilic layer. In humid environments or applications with prolonged water contact, it prevents hydrophilic groups from detaching or migrating, ensuring long-term stability of hydrophilicity.

[0013] In this invention, the hydrophobic monomers are a combination of methyl methacrylate and isobutyl methacrylate. While polymer chains formed by the polymerization of a single hydrophobic monomer (such as methyl methacrylate, MMA) have high rigidity and can improve polymer hardness, they also lead to insufficient toughness and low elongation at break, affecting subsequent processing and molding performance. This invention uses a hydrophobic composite of MMA and isobutyl methacrylate (IBMA), achieving an optimized balance of mechanical properties through differentiated synergistic chain segment structures: the methyl (-CH3) groups on the MMA molecular chain have low steric hindrance, resulting in highly regular chain segments after polymerization, which can impart good rigidity and tensile strength to the polymer, ensuring the material's load-bearing capacity; the isobutyl groups on the IBMA molecular chain (-CH3)... Greater steric hindrance can disrupt the overly regular arrangement of MMA segments during polymerization, introducing a suitable amount of segment defects. These defects can act as a "buffer space" for segment movement, improving the flexibility of the polymer molecular chain, thereby increasing elongation at break and improving the material's impact resistance and processing fluidity. From a compatibility perspective, both MMA and IBMA are acrylate monomers with high structural similarity and excellent copolymer compatibility, forming uniform copolymer segments and avoiding phase separation problems that may occur in single hydrophobic monomer systems. The composite hydrophobic and composite hydrophilic segments can also achieve good compatibility through the polar interaction of ester groups (-COO-), ensuring the uniformity of the overall polymer structure and laying the foundation for improved comprehensive performance.

[0014] Preferably, the mass ratio of hydroxyethyl methacrylate to polyethylene glycol methacrylate in the hydrophilic monomer is (6-10):1 (for example, it can be 6:1, 7:1, 8:1, 9:1, 10:1, etc.).

[0015] Preferably, the mass ratio of methyl methacrylate to isobutyl methacrylate in the hydrophobic monomer is (1.5-3):1 (for example, it can be 1.5:1, 2:1, 2.5:1, 3:1, etc.).

[0016] Preferably, the crosslinking agent comprises any one or a combination of at least two of polyethylene glycol dimethacrylate, ethylene glycol di(meth)acrylate, diethylene glycol di(meth)acrylate, or triethylene glycol di(meth)acrylate.

[0017] Preferably, the amount of crosslinking agent in the preparation raw materials is 0.01-2 wt% (for example, it can be 0.01 wt%, 0.05 wt%, 0.1 wt%, 0.5 wt%, 1 wt%, 1.5 wt%, 2 wt%, etc.).

[0018] Preferably, the ultraviolet absorbing monomer includes any one or a combination of two of 2-(2'-hydroxy-5'-methacryloyloxyethylphenyl)-2H-benzotriazole or 2,2'-dihydroxy-4,4'-dimethoxybenzophenone.

[0019] Preferably, the amount of ultraviolet-absorbing monomer used in the preparation raw materials is 0.1-1 wt% (for example, it can be 0.1 wt%, 0.2 wt%, 0.5 wt%, 0.8 wt%, 1 wt%, etc.).

[0020] Preferably, the blue light absorbing monomer comprises 4-[(E)-phenyldiazeninyl]phenyl-2-methacrylate.

[0021] Preferably, the amount of blue light absorbing monomer used in the preparation raw materials is 0.01-2 wt% (for example, it can be 0.01 wt%, 0.05 wt%, 0.1 wt%, 0.5 wt%, 1 wt%, 1.5 wt%, 2 wt%, etc.).

[0022] Preferably, the initiator comprises any one or a combination of at least two of azobisisobutyronitrile, 2,2'-azobisisobutyronitrile, or 2,2'-azobisisovalerate.

[0023] Preferably, the amount of initiator in the preparation raw materials is 0.01-2 wt% (for example, it can be 0.01 wt%, 0.05 wt%, 0.1 wt%, 0.5 wt%, 1 wt%, 1.5 wt%, 2 wt%, etc.).

[0024] In a second aspect, the present invention provides a method for preparing an artificial corneal endothelial sheet according to the first aspect, the method comprising: mixing a hydrophilic monomer, a hydrophobic monomer, a crosslinking agent, an ultraviolet absorbing monomer, a blue light absorbing monomer and an initiator, subjecting the mixture to a polymerization reaction, and then machining it to obtain the artificial corneal endothelial sheet.

[0025] In this invention, the components are mixed and poured into a mold for polymerization reaction. Then, conventional methods such as lathes and milling machines are used to process and shape the artificial corneal endothelial graft.

[0026] Preferably, the polymerization reaction is carried out at a temperature of 50-120°C (e.g., 50°C, 60°C, 80°C, 100°C, 120°C, etc.) and for a time of 20-36 hours (e.g., 20 hours, 24 hours, 28 hours, 32 hours, 36 hours, etc.).

[0027] Preferably, the polymerization reaction is followed by a purification operation: the product after the reaction is mixed with an organic solvent for extraction to remove impurities.

[0028] Preferably, the organic solvent includes any one or a combination of at least two of methanol, ethanol, isopropanol, acetone or ethylene glycol, with methanol being the most preferred.

[0029] In this invention, the mechanism of organic solvent extraction for impurity removal is as follows: First, solvent molecules penetrate into the polymer, and their polarity interacts with the hydrophilic segments in the polymer, "opening up" the originally tight network and expanding the internal free volume, creating the physical conditions for subsequent diffusion. Next, the unreacted monomers encapsulated inside come into contact with the solvent. Due to their excellent solubility, these monomers rapidly dissolve in the solvent and diffuse along the opened network channels from the inside of the material to the large amount of solvent on the outside, relying on the concentration gradient. After extraction, the organic solvent can be removed by heating to evaporate or by immersion in water to displace the organic solvent, thus removing any residual organic solvent from the product.

[0030] In this invention, compared with other solvents, methanol has a high solubility for residual substances in the reaction system, can quickly penetrate the polymer matrix, efficiently remove trace amounts of residual monomers, and has high extraction efficiency; at the same time, it is non-reactive with the polymer, does not swell or damage the structure and properties of hydrophilic acrylates, and is easy to separate and recover from the polymer; therefore, it can be used as the preferred impurity removal solvent of this invention.

[0031] Thirdly, the present invention provides the application of the artificial corneal endothelial graft according to the first aspect in the preparation of medical devices for relieving or treating corneal lesions.

[0032] Compared with the prior art, the present invention has at least the following beneficial effects:

[0033] The artificial corneal endothelial patch provided by this invention, by adjusting the ratio of hydrophilic monomers and hydrophobic monomers and rationally compounding the two monomers, results in an artificial corneal endothelial patch with moderate water content, excellent mechanical properties, adhesion properties and swelling stability, and can be used as a medical device to relieve or treat corneal lesions. Detailed Implementation

[0034] To facilitate understanding of the present invention, the following embodiments are provided. Those skilled in the art should understand that these embodiments are merely illustrative and should not be construed as limiting the scope of the invention.

[0035] The English abbreviations and sources of the materials used in the following embodiments are as follows:

[0036] Hydroxyethyl methacrylate: HEMA;

[0037] Polyethylene glycol methacrylate (PEGMA), purchased from Titan;

[0038] Methyl methacrylate (MMA);

[0039] Isobutyl methacrylate: IBMA;

[0040] Ethylene glycol dimethacrylate: EGDMA;

[0041] 2-(2'-hydroxy-5'-methacryloyloxyethylphenyl)-2H-benzotriazole: UV090;

[0042] 4-[(E)-Phenylenyl]phenyl-2-methacrylate: BL01, CAS number 128818-49-5;

[0043] Azobisisoheptanenitrile: AMVN.

[0044] Example 1

[0045] This embodiment provides an artificial corneal endothelial patch, the raw materials of which, by mass parts, include 87 parts of hydrophilic monomers (HEMA and PEGMA in a mass ratio of 8:1), 12 parts of hydrophobic monomers (MMA and IBMA in a mass ratio of 2.3:1), 0.2 parts of crosslinking agent (EGDMA), 0.5 parts of ultraviolet absorbing monomer (UV090), 0.1 parts of blue light absorbing monomer (BL01), and 0.2 parts of initiator (AMVN).

[0046] The method for preparing the artificial corneal endothelial sheet includes: mixing and casting the above components, polymerizing them at 50°C for 36 hours, then soaking the product in methanol for extraction and impurity removal for 4 hours, then soaking it in purified water to remove methanol, and finally machining it to obtain the artificial corneal endothelial sheet.

[0047] Example 2

[0048] This embodiment provides an artificial corneal endothelial patch, the raw materials of which, by mass parts, include 80 parts of hydrophilic monomers (HEMA and PEGMA in a mass ratio of 6:1), 19 parts of hydrophobic monomers (MMA and IBMA in a mass ratio of 3:1), 0.1 parts of crosslinking agent (EGDMA), 0.2 parts of ultraviolet absorbing monomer (UV090), 0.3 parts of blue light absorbing monomer (BL01), and 0.4 parts of initiator (AMVN).

[0049] The method for preparing the artificial corneal endothelial sheet includes: mixing and casting the above components, polymerizing them at 80°C for 28 hours, then soaking the product in methanol for extraction and impurity removal for 4 hours, followed by purification soaking to remove methanol, and then machining to obtain the artificial corneal endothelial sheet.

[0050] Example 3

[0051] This embodiment provides an artificial corneal endothelial patch, the raw materials of which, by mass parts, include 94 parts of hydrophilic monomers (HEMA and PEGMA in a mass ratio of 10:1), 5 parts of hydrophobic monomers (MMA and IBMA in a mass ratio of 1.5:1), 0.3 parts of crosslinking agent (EGDMA), 0.6 parts of ultraviolet absorbing monomer (UV090), 0.05 parts of blue light absorbing monomer (BL01), and 0.05 parts of initiator (AMVN).

[0052] The method for preparing the artificial corneal endothelial sheet includes: mixing and casting the above components, polymerizing them at 120°C for 20 hours, then soaking the product in methanol for extraction and impurity removal for 8 hours, then soaking it in purified water to remove methanol, and finally machining it to obtain the artificial corneal endothelial sheet.

[0053] Example 4

[0054] This embodiment provides an artificial corneal endothelial graft, which differs from Embodiment 1 only in that the solvent for extraction and impurity removal is replaced with an equal amount of ethanol in the preparation method, while the rest is the same as in Embodiment 1.

[0055] Example 5

[0056] This embodiment provides an artificial corneal endothelial graft, which differs from Embodiment 1 only in that the solvent used for extraction and impurity removal is replaced with an equal amount of isopropanol in the preparation method, while the rest is the same as in Embodiment 1.

[0057] Example 6

[0058] This embodiment provides an artificial corneal endothelial graft, which differs from Example 1 only in that the solvent for extraction and impurity removal is replaced with an equal amount of acetone in the preparation method, while the rest is the same as in Example 1.

[0059] Example 7

[0060] This embodiment provides an artificial corneal endothelial graft, which differs from Embodiment 1 only in that the solvent used for extraction and impurity removal is replaced with an equal amount of ethylene glycol in the preparation method, while other aspects are the same as in Embodiment 1.

[0061] Comparative Example 1

[0062] This comparative example provides an artificial corneal endothelial patch, which differs from Example 1 only in that the hydrophilic monomer is 87 parts by weight (HEMA and PEGMA in a mass ratio of 8:1) and the hydrophobic monomer is 12 parts by weight (MMA and IBMA in a mass ratio of 2.3:1), and the rest is the same as in Example 1.

[0063] Comparative Example 2

[0064] This comparative example provides an artificial corneal endothelial patch, which differs from Example 1 only in that the hydrophilic monomer is 97 parts by mass (HEMA and PEGMA in a mass ratio of 8:1) and the hydrophobic monomer is 2 parts by mass (MMA and IBMA in a mass ratio of 2.3:1), and the rest is the same as in Example 1.

[0065] Comparative Example 3

[0066] This comparative example provides an artificial corneal endothelial patch, which differs from Example 1 only in that the hydrophilic monomer is HEMA, 87 parts by weight, and the other aspects are the same as in Example 1.

[0067] Comparative Example 4

[0068] This comparative example provides an artificial corneal endothelial patch, which differs from Example 1 only in that the hydrophilic monomer is PEGMA, 87 parts by weight, and the other aspects are the same as in Example 1.

[0069] Comparative Example 5

[0070] This comparative example provides an artificial corneal endothelial patch, which differs from Example 1 only in that the hydrophobic monomer is only MMA, 12 parts by weight, and the other aspects are the same as in Example 1.

[0071] Comparative Example 6

[0072] This comparative example provides an artificial corneal endothelial patch, which differs from Example 1 only in that the hydrophobic monomer is IBMA, 12 parts by weight, and the rest is the same as in Example 1.

[0073] Test case

[0074] Performance testing

[0075] (1) Moisture content test

[0076] After equilibrating the sample at 23℃ and 50% relative humidity for 24 hours, it was weighed (W1). Then it was immersed in deionized water at 37℃ for 24 hours. After the surface moisture was absorbed, it was weighed (W2). The formula for calculating the water content is: water content (%) = (W2-W1) / W1×100%.

[0077] (2) Mechanical property testing

[0078] (2.1) Tensile strength and elongation at break

[0079] Dumbbell-shaped specimens (0.5 mm thick, 25 mm gauge length) were prepared and tested using a universal testing machine at a tensile speed of 5 mm / min. Five specimens were tested in each group, and the average value was taken.

[0080] (2.2) Hardness test

[0081] Using a Shore A hardness tester, five test points were evenly selected on the sample surface, and the average value was taken.

[0082] (3) Adhesion performance test

[0083] (3.1) Adhesion force test

[0084] A biomimetic matrix layer (simulating the corneal stroma material with a surface roughness Ra=0.2μm) was used. The sample was cut into 10mm×10mm sizes and attached to the surface of the biomimetic matrix layer in a humid environment at 37℃. A tensile testing machine was used to vertically peel the sample at a speed of 1mm / min and the peeling force was recorded. Five samples were tested in each group and the average value was taken.

[0085] (3.2) Displacement stability test

[0086] The sample after (3.1) bonding was placed in a swing device simulating eye movement (swing angle ±15°, frequency 1 time / 10s), and ran continuously for 24h in a humid environment at 37℃. The sample was observed to see if it shifted or fell off, and the stability level was recorded (A grade: no shift; B grade: slight shift ≤1mm; C grade: obvious shift >1mm; D grade: fall off).

[0087] (4) Swelling stability test

[0088] Immerse the sample in 37℃ deionized water and remove it after 1h, 24h and 72h respectively. After drying the surface moisture, weigh it and calculate the swelling rate (swelling rate = (mass after immersion - initial mass) / initial mass × 100%). Observe whether the sample shows excessive swelling, deformation or damage.

[0089] (5) Residual monomer content test

[0090] Preparation of standard solutions:

[0091] Take six 100mL volumetric flasks and weigh 0.1g each of HEMA, PEGMA, EGDMA, MMA, IBMA, and AMVN into each flask. Dilute to volume with acetone to prepare a stock solution with a concentration of 1000μg / mL. Dilute the stock solution with acetone to create five standard solutions with concentrations of 1μg / mL, 2μg / mL, 5μg / mL, 10μg / mL, and 20μg / mL for use.

[0092] Take two 100mL volumetric flasks, weigh 0.1g each of UV090 and BL01, dissolve them in acetone and bring the volume to 100mL to prepare a stock solution with a concentration of 1000μg / mL. Dilute the stock solution to five standard solutions with concentrations of 1μg / mL, 2μg / mL, 5μg / mL, 10μg / mL, and 20μg / mL for later use.

[0093] The sample was subjected to extreme extraction according to the method specified in Appendix A of YY0290.5-2023 to obtain an extract solution.

[0094] The above standard solutions and extraction solutions were detected by gas chromatography or liquid chromatography. The gas chromatography detection conditions for HEMA, PEGMA, and EGDMA (volatile monomers) are shown in Table 1.

[0095] Table 1

[0096]

[0097] The gas chromatographic detection conditions for AMVN (volatile monomers) are shown in Table 2.

[0098] Table 2

[0099]

[0100] The liquid chromatography detection conditions for MMA and IBMA (weakly volatile / non-volatile) are shown in Table 3.

[0101] Table 3

[0102]

[0103] The detection conditions for UV090 and BL01 (weakly volatile / non-volatile) liquid chromatography are shown in Table 4.

[0104] Table 4

[0105]

[0106] The artificial corneal endothelial patches prepared in Examples 1-3 and Comparative Examples 1-6 were subjected to the above-mentioned tests on water content, mechanical properties, adhesion properties and swelling stability. The results are summarized in Tables 5 and 6.

[0107] Table 5

[0108]

[0109] Table 6

[0110]

[0111] After removing impurities from the artificial corneal endothelial grafts in Examples 1 and 4-7 using organic solvents, the final products were tested for residual monomer content, and the results are shown in Table 7.

[0112] Table 7

[0113]

[0114] The test results show that, by controlling the ratio and composition of hydrophilic and hydrophobic monomers, the artificial corneal endothelial patch obtained by this invention has a moderate water content; balanced tensile strength and elongation at break; moderate hardness; low impact breakage rate; and good rigidity and flexibility. It also exhibits moderate adhesion, tightly adhering to the matrix layer without displacement after 24 hours, demonstrating excellent stability. Swelling reaches equilibrium after 24 hours, resulting in structural stability. Furthermore, the monomer residue is low. Specifically, the water content is 22.2-30.5%, the tensile strength is 19.6-25.5 MPa, the elongation at break is 22.2-30.3%, the Shore A hardness is 70-80, and the average peel force is 2.1-2.5 N / cm. 2 The displacement stability level is A. The swelling rate is 10.2-15.6% in 1 hour, 25.3-30.3% in 24 hours, and 27.1-32.7% in 72 hours. The appearance after 72 hours is slight swelling and no deformation. The total residual amount is 11.7-134.2 ppm.

[0115] A comparison of Examples 1 and 4-7 shows that methanol exhibits better solubility for monomers compared to ethanol, isopropanol, acetone, and ethylene glycol, enabling efficient and thorough removal of unreacted monomers. Furthermore, methanol's viscosity (0.54 mPa·s, 25°C) is significantly lower than that of ethanol (1.2 mPa·s), n-propanol (2.2 mPa·s), and ethylene glycol (16.1 mPa·s), and its surface tension (22.6 mN / m) is lower than that of ethanol (22.8 mN / m), allowing for rapid penetration into the polymer matrix and shortening the extraction time.

[0116] A comparison between Example 1 and Comparative Example 1 shows that:

[0117] Moisture content: Due to the high proportion of hydrophobic segments and the dense network structure, it is difficult to absorb sufficient moisture, resulting in excessively low moisture content; Mechanical properties: Due to the high proportion of hydrophobic segments, the tensile strength and hardness are high, but the elongation at break is extremely low, the impact resistance is poor, the rigidity is too strong, and it is prone to brittleness; Adhesion performance: Due to the high proportion of hydrophobic segments and the excessive rigidity, it cannot adhere to the surface of the matrix layer during adhesion, the peel force is low, and it is easy to shift; Swelling stability: Due to the high proportion of hydrophobic segments, the swelling rate is low, but the rigidity is too strong, which is not an ideal state.

[0118] A comparison between Example 1 and Comparative Example 2 shows that:

[0119] Water content: Due to the excessive proportion of hydrophilic segments and insufficient cross-linking density, excessive swelling leads to excessive water content; Mechanical properties: Due to the excessive proportion of hydrophilic segments, the elongation at break is high and the material is soft, but the tensile strength and hardness are insufficient, resulting in weak mechanical strength and inability to meet load-bearing requirements; Adhesion performance: Due to the excessive proportion of hydrophilic segments, the material is excessively swollen and soft, resulting in weak adhesion and complete detachment during simulated motion; Swelling stability: Due to the excessive proportion of hydrophilic segments, the swelling rate continues to increase, the structure is unstable, and the barrier function fails.

[0120] A comparison of Example 1 and Comparative Examples 3-6 shows that:

[0121] Water content: Due to the single hydrophilic-hydrophobic system, the hydrophilic and hydrophobic groups are unevenly distributed, resulting in poor water absorption efficiency; Mechanical properties: Tensile strength and elongation at break are reduced, and the single monomer chain segment structure leads to an imbalance in mechanical properties; Adhesion properties: Due to the single hydrophilic-hydrophobic system, the hydrophilic and hydrophobic groups are unevenly distributed, and some areas are not tightly adhered, resulting in slight displacement; Swelling stability: The single hydrophilic-hydrophobic chain segment leads to an uneven network structure and poor swelling uniformity.

[0122] The applicant declares that the above description is only a specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Those skilled in the art should understand that any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention fall within the protection and disclosure scope of the present invention.

Claims

1. An artificial corneal endothelial graft, characterized in that, The raw materials for preparing the artificial corneal endothelial graft include: hydrophilic monomers, hydrophobic monomers, crosslinking agents, ultraviolet absorbing monomers, blue light absorbing monomers, and initiators; The hydrophilic monomer includes a combination of hydroxyethyl methacrylate and polyethylene glycol methacrylate, and the hydrophobic monomer includes a combination of methyl methacrylate and isobutyl methacrylate. In the preparation raw materials, the amount of hydrophilic monomer is 80-94 wt%, and the amount of hydrophobic monomer is 5-19 wt%.

2. The artificial corneal endothelial graft according to claim 1, characterized in that, The mass ratio of hydroxyethyl methacrylate to polyethylene glycol methacrylate in the hydrophilic monomer is (6-10):1; The mass ratio of methyl methacrylate to isobutyl methacrylate in the hydrophobic monomer is (1.5-3):

1.

3. The artificial corneal endothelial graft according to claim 1, characterized in that, The crosslinking agent includes any one or a combination of at least two of polyethylene glycol dimethacrylate, ethylene glycol di(meth)acrylate, diethylene glycol di(meth)acrylate or triethylene glycol di(meth)acrylate; The amount of crosslinking agent used in the preparation raw materials is 0.01-2 wt%.

4. The artificial corneal endothelial graft according to claim 1, characterized in that, The ultraviolet-absorbing monomer includes any one or a combination of two of 2-(2'-hydroxy-5'-methacryloyloxyethylphenyl)-2H-benzotriazole or 2,2'-dihydroxy-4,4'-dimethoxybenzophenone. The amount of ultraviolet-absorbing monomer used in the preparation raw materials is 0.1-1 wt%.

5. The artificial corneal endothelial graft according to claim 1, characterized in that, The blue light absorbing monomer includes 4-[(E)-phenyldiazeninyl]phenyl-2-methacrylate; The amount of blue light absorbing monomer used in the preparation raw materials is 0.01-2 wt%.

6. The artificial corneal endothelial graft according to claim 1, characterized in that, The initiator includes any one or a combination of at least two of azobisisobutyronitrile, 2,2'-azobisisobutyronitrile, or 2,2'-azobisisovalerate. The amount of initiator used in the preparation raw materials is 0.01-2 wt%.

7. A method for preparing an artificial corneal endothelial graft according to any one of claims 1-6, characterized in that, The preparation method includes: mixing hydrophilic monomers, hydrophobic monomers, crosslinking agents, ultraviolet absorbing monomers, blue light absorbing monomers and initiators, performing a polymerization reaction, and then machining to obtain the artificial corneal endothelial sheet.

8. The preparation method according to claim 7, characterized in that, The polymerization reaction is carried out at a temperature of 50-120℃ for a time of 20-36 hours.

9. The preparation method according to claim 7, characterized in that, The polymerization reaction is followed by a purification process: the product after the reaction is mixed with methanol for extraction to remove impurities.

10. The use of an artificial corneal endothelial graft according to any one of claims 1-6 in the preparation of a medical device for relieving or treating corneal lesions.

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