Preparation method of high-strength antibacterial silk fibroin contact lenses
By mixing chitosan nanofibers and quaternized chitosan nanofibers with silk fibroin to form a three-dimensional reinforcing network, the problems of insufficient mechanical and antibacterial properties of silk fibroin contact lenses are solved, and high-strength and antibacterial silk fibroin contact lenses are prepared.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- GANSU KANGSHILI CONTACT LENS CO LTD
- Filing Date
- 2026-04-08
- Publication Date
- 2026-05-12
AI Technical Summary
Existing silk fibroin contact lenses have insufficient mechanical properties, making them prone to microcracks and tears, and their antibacterial properties are poor, affecting wearing comfort and safety.
Chitosan nanofibers and quaternized chitosan nanofibers are mixed with silk fibroin to form a three-dimensional reinforced network, and a high-strength antibacterial structure is constructed by combining acrylamide molecules through gradient air drying.
It significantly improves the mechanical properties and antibacterial ability of silk fibroin contact lenses, enhances lens durability and transparency, and ensures safety and comfort during wear.
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Abstract
Description
Technical Field
[0001] This invention relates to the field of corneal contact lens technology, and more particularly to a method for preparing a high-strength antibacterial silk fibroin contact lens. Background Technology
[0002] In the technological development of contact lens materials, silk fibroin has become an important biomaterial direction to replace traditional synthetic polymer materials (such as polymethyl methacrylate, silicone hydrogel, etc.) due to its excellent biocompatibility, optical transparency and renewable properties derived from natural silk. Related preparation schemes have been disclosed.
[0003] Existing technologies typically use pure silk fibroin solutions to fabricate contact lenses through methods such as casting, molding, or spin casting. While these methods achieve basic optical functions and biocompatibility, their core drawback lies in the insufficient inherent mechanical properties of the material, severely limiting the practicality and durability of the products. Specifically, the gel or solid film network structure formed by pure silk fibroin is relatively homogeneous and lacks an effective reinforcing phase, resulting in low key mechanical properties such as tensile strength, elongation at break, and elastic modulus. In actual use, microcracks, plastic deformation, and even tearing can easily occur due to daily wear, rubbing, or cleaning, making it difficult to maintain the dimensional stability and structural integrity of the lenses over the long term.
[0004] Furthermore, the weak mechanical properties limit the possibilities for lens design, making it impossible to achieve both ultra-thinness and high oxygen permeability while maintaining sufficient mechanical toughness, thus affecting wearing comfort and safety. Existing publicly available solutions attempt to optimize the material by changing the concentration of silk fibroin, the type of cross-linking agent, or processing parameters, but these adjustments offer limited improvements in mechanical properties and come at the cost of sacrificing transparency, oxygen permeability, or biocompatibility, failing to fundamentally solve the problem of insufficient material strength and toughness.
[0005] Furthermore, prolonged wear of contact lenses can easily lead to the growth of microorganisms on the lens surface. Especially with the combined effects of tears, protein deposits, and environmental microorganisms, bacteria such as Staphylococcus aureus and Escherichia coli can easily adhere and form biofilms that are difficult to remove. Although silk fibroin itself possesses some antibacterial potential, it cannot meet the antibacterial requirements of contact lenses.
[0006] Therefore, how to provide a method for preparing high-strength antibacterial silk fibroin contact lenses, improve the durability and mechanical strength of silk fibroin contact lenses, and at the same time endow them with excellent antibacterial properties is a problem that urgently needs to be solved in this field. Summary of the Invention
[0007] In view of this, the present invention provides a method for preparing a high-strength antibacterial silk fibroin contact lens to solve the problems of poor mechanical properties and low antibacterial strength of existing silk fibroin contact lenses.
[0008] To achieve the above objectives, the present invention adopts the following technical solution: A method for preparing a high-strength antibacterial silk fibroin contact lens includes the following steps: 1) Degumming is performed on silkworm silk, which is then dissolved in lithium bromide solution to obtain silk fibroin solution; 2) Mix the silk fibroin solution with the chitosan nanofiber solution and the quaternized chitosan nanofiber to obtain a silk fibroin-chitosan nanofiber-quaternized chitosan nanofiber mixed solution; 3) Mix the silk fibroin-chitosan nanofiber-quaternized chitosan nanofiber mixed solution with an acrylamide solution to obtain a quaternary blend; 4) The obtained quaternary blend solution is transferred to a contact lens mold and then subjected to gradient air drying to obtain silk fibroin contact lenses.
[0009] Preferably, the degumming process in step 1) includes: placing the silkworm silk in a sodium carbonate solution for degumming; The pH value of the sodium carbonate solution is 10-11; The degumming process is carried out under boiling conditions for 25-35 minutes.
[0010] Preferably, the molar concentration of the lithium bromide solution in step 1) is 9.3 mol / L; The mass concentration of the silk fibroin solution is 5-10%.
[0011] Preferably, in step 2), the mass ratio of the sum of chitosan nanofibers and quaternized chitosan nanofibers in the chitosan nanofiber solution and the silk fibroin in the silk fibroin solution is 1~3:100. The mass ratio of chitosan nanofibers to quaternized chitosan nanofibers is 60~80:20~40; The mass concentrations of the chitosan nanofiber solution and the quaternized chitosan nanofiber solution are independently 0.45-3%; Among them, the diameters of chitosan nanofibers and quaternized chitosan nanofibers are 10~50 nm and the lengths are 0.5~3 μm.
[0012] Preferably, the pH value of the mixture in step 2) is 5.5~6.5, the mixing speed is 300~500 rpm, and the mixing time is 10~24h.
[0013] Preferably, in step 3), the mass ratio of the solute in the silk fibroin-chitosan nanofiber-quaternized chitosan nanofiber mixed solution to the acrylamide in the acrylamide solution is 100:15~30. The mixing speed is 300~500 rpm, and the mixing time is 40~80 min.
[0014] Preferably, the gradient drying process includes sequential high-humidity drying, dehumidification drying, and low-humidity drying.
[0015] Preferably, the high-humidity air-drying treatment is performed at room temperature, with a relative humidity of 70-75%, for a duration of 6-12 hours. The temperature of the dehumidification and air-drying treatment is 25~30℃, the relative humidity decreases linearly, the endpoint of the relative humidity decrease is 35~40%, and the time is 6~7 hours; The low-humidity air-drying treatment is carried out under dry conditions, at a temperature of 25~30℃, for a time of 12~48h.
[0016] Another object of the present invention is to provide a high-strength antibacterial silk fibroin contact lens prepared by the above preparation method.
[0017] This invention primarily utilizes the excellent mechanical properties of chitosan nanofibers and their multiple, synergistic interfacial interactions with silk fibroin molecules to construct a three-dimensional interpenetrating reinforcement network with acrylamide molecules, thereby achieving fundamental material strengthening at the nanoscale. Furthermore, by partially replacing chitosan nanofibers with quaternized chitosan nanofibers and introducing positively charged quaternary ammonium salt groups, the antibacterial properties are enhanced.
[0018] As can be seen from the above technical solution, compared with the prior art, the present invention has the following beneficial effects: 1. The chitosan nanofibers and quaternized chitosan nanofibers added in this invention can generate interfacial interactions with silk fibroin, including hydrogen bonding and electrostatic interactions. The hydroxyl, amino, and carbon-oxygen double bond groups of silk fibroin can form a dense hydrogen bond network with the hydroxyl and amino groups in chitosan. Furthermore, the positively charged groups in the chitosan nanofibers can also form electrostatic interactions with the negatively charged amino acid residues in silk fibroin, further enhancing the binding force between the chitosan nanofibers and silk fibroin. Based on these interactions, when subjected to force, stress can be efficiently transferred from silk fibroin to the rigid chitosan nanofibers, thereby increasing the mechanical properties of contact lenses.
[0019] 2. Chitosan nanofibers possess a regular molecular chain structure and abundant functional groups on their surface, which may serve as additional and effective heterogeneous nucleation sites. This can guide silk fibroin molecules to accumulate more orderly and rapidly on their surface, forming β-sheet crystals, and synergistically induce crystallization with acrylamide through blending. The dual induction by chitosan nanofibers and acrylamide contributes to a more uniform crystal size distribution, thereby achieving superior mechanical properties.
[0020] 3. The introduction of quaternized chitosan nanofibers enables highly efficient, pH-independent contact sterilization, significantly improving antibacterial performance. Its hydrophilicity and biocompatibility are highly compatible with the system, and its light transmittance is not impaired after uniform dispersion through blending. This achieves precise synergy of antibacterial, reinforcing, and optical properties at the molecular level, upgrading the material from passive tolerance to active defense. Detailed Implementation
[0021] This invention provides a method for preparing high-strength antibacterial silk fibroin contact lenses, comprising the following steps: 1) Degumming is performed on silkworm silk, which is then dissolved in lithium bromide solution to obtain silk fibroin solution; 2) Mix the silk fibroin solution with the chitosan nanofiber solution and the quaternized chitosan nanofiber to obtain a silk fibroin-chitosan nanofiber-quaternized chitosan nanofiber mixed solution; 3) Mix the silk fibroin-chitosan nanofiber-quaternized chitosan nanofiber mixed solution with an acrylamide solution to obtain a quaternary blend; 4) The obtained quaternary blend solution is transferred to a contact lens mold and then subjected to gradient air drying to obtain silk fibroin contact lenses.
[0022] In this invention, the degumming process in step 1) includes: placing the silkworm silk in a sodium carbonate solution for degumming; the pH value of the sodium carbonate solution is 10~11, specifically 10.2, 10.4, 10.5, 10.6, or 10.8; the pH value of the system will decrease after mixing with the silkworm silk.
[0023] In this invention, the degumming process is carried out under boiling conditions, and the degumming time is 25-35 minutes, specifically 26 minutes, 28 minutes, 30 minutes, 32 minutes, or 34 minutes.
[0024] In this invention, the molar concentration of the lithium bromide solution in step 1) is 9.3 mol / L.
[0025] In this invention, the mass concentration of the silk fibroin solution is 5-10%, specifically 6%, 7%, 8%, or 9%.
[0026] In this invention, the mass ratio of the chitosan nanofibers and quaternized chitosan nanofibers in the chitosan nanofiber solution and the quaternized chitosan nanofiber solution in step 2) to the silk fibroin in the silk fibroin solution is 1~3:100, preferably 1.5~2.5:100, and more preferably 2:100.
[0027] In this invention, the mass ratio of chitosan nanofibers to quaternized chitosan nanofibers is 60-80:20-40, preferably 65-75:25-35, and more preferably 70:30. Excessive addition of quaternized chitosan nanofibers can lead to an excessively high positive charge density, irritating epithelial cells and non-specifically adsorbing tear proteins, thus affecting lens comfort.
[0028] In this invention, the mass concentrations of the chitosan nanofiber solution and the quaternized chitosan nanofiber solution are independently 0.45-3%, specifically 0.5%, 0.6%, 0.8%, 1%, 1.2%, 1.5%, 1.8%, 2%, 2.2%, 2.5%, and 2.8%; wherein the diameters of the chitosan nanofibers and the quaternized chitosan nanofibers are independently 10-50 nm, specifically 15 nm, 20 nm, 25 nm, 30 nm, 35 nm, 40 nm, and 45 nm; and the lengths are independently 0.5-3 μm, specifically 0.6 μm, 0.8 μm, 1 μm, 1.2 μm, 1.5 μm, 1.8 μm, 2 μm, 2.2 μm, 2.5 μm, and 2.8 μm. The chitosan nanofibers of the particle size described in this invention have a high specific surface area and a suitable length, which can generate maximum interfacial interactions (hydrogen bonds, electrostatic interactions) with the silk fibroin matrix, entangle with each other, form an effective three-dimensional reinforcing network, and improve mechanical properties. In addition, the diameter of the chitosan nanofibers is much smaller than the wavelength of visible light, which can avoid light scattering and maintain the high transparency of the lens. During the research, it was found that when the diameter is greater than 100 nm, the lens haze will increase significantly.
[0029] In this invention, the degree of quaternization of the quaternized chitosan nanofibers is preferably 40-70%, specifically 45%, 50%, 55%, 60%, or 65%; the quaternized chitosan is preferably hydroxypropyltrimethylammonium chloride chitosan.
[0030] In this invention, the pH value of the mixture in step 2) is 5.5~6.5, specifically 5.6, 5.8, 6, 6.2, or 6.4; the mixing speed is 300~500 rpm, specifically 320 rpm, 350 rpm, 380 rpm, 400 rpm, 420 rpm, 450 rpm, or 480 rpm; and the mixing time is 10~24 h, specifically 12 h, 15 h, 18 h, or 20 h. At the pH value specified in this invention, the amino groups of the chitosan nanofibers are protonated, forming electrostatic repulsion with the positively charged quaternary ammonium groups of the quaternized chitosan nanofibers. This helps prevent aggregation between dissimilar fibers and promotes subsequent uniform dispersion.
[0031] In this invention, the mass ratio of the solute in the silk fibroin-chitosan nanofiber mixed solution to the acrylamide in the acrylamide solution in step 3) is 100:15~30, preferably 100:20~25, and more preferably 100:22.
[0032] In this invention, the mixing speed is 300~500 rpm, specifically 350 rpm, 400 rpm, or 450 rpm; the mixing time is 40~80 min, specifically 50 min, 60 min, or 70 min.
[0033] In this invention, the gradient drying process includes sequential high-humidity drying, dehumidification drying, and low-humidity drying.
[0034] In this invention, the high-humidity air-drying treatment is performed at room temperature with a relative humidity of 70-75%, specifically 71%, 72%, 73%, or 74%; the time is 6-12 hours, specifically 7 hours, 9 hours, 8 hours, 10 hours, or 11 hours. This process allows moisture to be slowly removed, preventing rapid shrinkage that could lead to internal stress and macroscopic cracks.
[0035] In this invention, the dehumidification and air-drying treatment temperature is 25~30℃, specifically 26℃, 27℃, 28℃, and 29℃; the relative humidity decreases linearly, with the endpoint of the relative humidity decrease being 35~40%, specifically 36%, 37%, 38%, and 39%; the time is 6~7 hours, specifically 6.2 hours, 6.4 hours, 6.5 hours, 6.6 hours, and 6.8 hours. This process induces β-lamellae crystallization. Before air-drying, silk fibroin and acrylamide can form a physically entangled nanofiber network with chitosan nanofibers. Silk fibroin is wrapped on the surface of chitosan nanofibers. During the air-drying process, the shrinkage of the silk fibroin matrix further "locks" this composite network, making the structure denser, reducing defects, and effectively preventing the generation and propagation of cracks.
[0036] In this invention, the low-humidity air-drying treatment is carried out under dry conditions at a temperature of 25~30℃, specifically 26℃, 27℃, 28℃, or 29℃; and for a time of 12~48h, specifically 18h, 24h, 30h, or 36h. This process densifies the lens, reduces light scattering, and makes the lens completely transparent or translucent.
[0037] The present invention also provides a high-strength antibacterial silk fibroin contact lens prepared by the above preparation method.
[0038] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.
[0039] Example 1
[0040] Silkworm silk was placed in a sodium carbonate solution with a pH of 10, and the solution was heated to boiling and maintained for 30 minutes to degummify the silkworm silk. Then, the treated silkworm silk was dissolved in a 9.3M lithium bromide solution, and after dialysis (with a molecular weight cutoff of 10,000 Daltons) and concentration, a 10% (w / w) silk fibroin solution was obtained.
[0041] A 1.05% (w / w) chitosan nanofiber solution (30 nm in diameter and 1.5 μm in length) and a 0.45% (w / w) hydroxypropyltrimethylammonium chloride chitosan nanofiber solution (55% quaternization, 30 nm in diameter and 1.5 μm in length) were prepared. Then, the silk fibroin solution and the chitosan nanofiber solution were mixed at a ratio of 1.5:100 (total chitosan nanofibers and quaternized chitosan nanofibers to silk fibroin). The pH was adjusted to 6, and the mixture was stirred at 300 rpm for 12 h to allow the silk fibroin and chitosan nanofibers to form a pre-binding.
[0042] The above mixed solution was then mixed with an acrylamide solution (mass concentration of 15%, mass ratio of acrylamide to solute in the mixed solution of 15:100) to obtain a blend. The blend was dropped into a contact lens mold, the humidity was adjusted to 75%, and it was air-dried for 8 hours. Then the temperature was slightly increased to 28°C, and the humidity was linearly reduced, dropping to 40% after 6 hours. The above temperature was maintained, and it was air-dried for another 12 hours in a desiccant environment to obtain silk fibroin contact lenses. The lenses were then repeatedly rinsed with sterile water and physiological saline to remove unbound monomers. The final silk fibroin contact lenses were stored in sterile physiological saline for later use.
[0043] Example 2
[0044] The difference between this embodiment and Embodiment 1 is that the mass ratio of chitosan nanofibers, quaternized chitosan nanofibers and silk fibroin is 0.35:0.15:100.
[0045] Example 3
[0046] The difference between this embodiment and Embodiment 1 is that the mass ratio of chitosan nanofibers, quaternized chitosan nanofibers and silk fibroin is 2.1:0.9:100.
[0047] Example 4
[0048] The difference between this embodiment and Embodiment 1 is that the mass ratio of chitosan nanofibers, quaternized chitosan nanofibers and silk fibroin is 1.2:0.3:100.
[0049] Example 5
[0050] The difference between this embodiment and Embodiment 1 is that the mass ratio of chitosan nanofibers, quaternized chitosan nanofibers and silk fibroin is 0.9:0.6:100.
[0051] Comparative Example 1
[0052] The difference between this comparative example and Example 1 is that no quaternized chitosan nanofibers were added, and the mass ratio of chitosan nanofibers to silk fibroin was 1.5:100.
[0053] Comparative Example 2
[0054] The only difference between this comparative example and Example 1 is that chitosan nanofibers and quaternized chitosan nanofibers are not added. Specifically, a 10% (w / w) silk fibroin solution is directly mixed with an acrylamide solution to prepare silk fibroin contact lenses.
[0055] Experimental Example 1
[0056] The relevant performance tests of the silk fibroin contact lenses prepared in Examples 1-5 and Comparative Examples 1-2 of this invention are shown in Table 1: Tensile breaking strength: GB / T1040-2006, Instrong 3365 universal testing machine; Transmittance: Ultraviolet-Visible absorption spectroscopy.
[0057] Table 1 Relevant performance test results
[0058] Table 1 shows that the silk fibroin contact lenses prepared according to this invention have higher tensile strength and light transmittance compared to the unmodified Comparative Example 2, meeting application requirements and the durability requirements of long-cycle replacement lenses. Compared with Comparative Example 1, it can be seen that partially replacing chitosan nanofibers with quaternized chitosan nanofibers did not affect the tensile strength; the elongation at break decreased slightly (approximately 8%), but still met the requirements for contact lenses in this field.
[0059] Experiment Example 2
[0060] The antibacterial rate and biocompatibility of Example 1 and Comparative Example 1 were tested, and the test results are shown in Table 2: Antibacterial rate: colony count method; Biocompatibility: CCK-8 assay (compared to blank control group).
[0061] Table 2 Antibacterial performance test
[0062] As can be seen from Table 2, the present invention significantly improves the antibacterial properties of silk fibroin contact lenses by adding quaternized chitosan nanofibers, while ensuring excellent biocompatibility.
[0063] The various embodiments in this specification are described in a progressive manner, with each embodiment focusing on the differences from other embodiments. The same or similar parts between the various embodiments can be referred to each other.
[0064] The above description of the disclosed embodiments enables those skilled in the art to make or use the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention. Therefore, the invention is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.
Claims
1. A method for preparing a high-strength antibacterial silk fibroin contact lens, characterized in that, Includes the following steps: 1) Degumming is performed on silkworm silk, which is then dissolved in lithium bromide solution to obtain silk fibroin solution; 2) Mix the silk fibroin solution with the chitosan nanofiber solution and the quaternized chitosan nanofiber to obtain a silk fibroin-chitosan nanofiber-quaternized chitosan nanofiber mixed solution; 3) Mix the silk fibroin-chitosan nanofiber-quaternized chitosan nanofiber mixed solution with an acrylamide solution to obtain a quaternary blend; 4) The obtained quaternary blend solution is transferred to a contact lens mold and then subjected to gradient air drying to obtain silk fibroin contact lenses.
2. The method for preparing a high-strength antibacterial silk fibroin contact lens according to claim 1, characterized in that, The degumming process described in step 1) includes: placing the silkworm silk in a sodium carbonate solution for degumming; The pH value of the sodium carbonate solution is 10-11; The degumming process is carried out under boiling conditions for 25-35 minutes.
3. The method for preparing a high-strength antibacterial silk fibroin contact lens according to claim 2, characterized in that, The molar concentration of the lithium bromide solution mentioned in step 1) is 9.3 mol / L; The mass concentration of the silk fibroin solution is 5-10%.
4. A method for preparing a high-strength antibacterial silk fibroin contact lens according to any one of claims 1 to 3, characterized in that, In step 2), the mass ratio of the chitosan nanofibers and quaternized chitosan nanofibers in the chitosan nanofiber solution and the silk fibroin in the silk fibroin solution is 1~3:
100. The mass ratio of chitosan nanofibers to quaternized chitosan nanofibers is 60~80:20~40; The mass concentrations of the chitosan nanofiber solution and the quaternized chitosan nanofiber solution are independently 0.45-3%; Among them, the diameters of chitosan nanofibers and quaternized chitosan nanofibers are 10~50 nm and the lengths are 0.5~3 μm.
5. The method for preparing a high-strength antibacterial silk fibroin contact lens according to claim 4, characterized in that, In step 2), the pH value of the mixture is 5.5-6.5, the mixing speed is 300-500 rpm, and the mixing time is 10-24 h.
6. The method for preparing a high-strength antibacterial silk fibroin contact lens according to claim 5, characterized in that, In step 3), the mass ratio of the solute in the silk fibroin-chitosan nanofiber-quaternized chitosan nanofiber mixed solution to the acrylamide in the acrylamide solution is 100:15~30. The mixing speed is 300~500 rpm, and the mixing time is 40~80 min.
7. A method for preparing a high-strength antibacterial silk fibroin contact lens according to claim 5 or 6, characterized in that, The gradient air-drying process includes sequential high-humidity air-drying, dehumidification air-drying, and low-humidity air-drying.
8. The method for preparing a high-strength antibacterial silk fibroin contact lens according to claim 7, characterized in that, The high-humidity air-drying treatment is performed at room temperature, with a relative humidity of 70-75%, for a duration of 6-12 hours. The temperature of the dehumidification and air-drying treatment is 25~30℃, the relative humidity decreases linearly, the endpoint of the relative humidity decrease is 35~40%, and the time is 6~7 hours; The low-humidity air-drying treatment is carried out under dry conditions, at a temperature of 25~30℃, for a time of 12~48h.
9. High-strength antibacterial silk fibroin contact lenses prepared by the preparation method according to any one of claims 1 to 8.