Preparation process of hyaluronic acid-chitosan coating and contact lens with hyaluronic acid-chitosan coating

Abstract

The invention provides a preparation process of a hyaluronic acid-chitosan coating and a contact lens with the hyaluronic acid-chitosan coating, and belongs to the technical field of surface coatings of contact lenses. The preparation method comprises the following steps: carrying out surface grafting treatment on a bare contact lens with high oxygen permeation rate, and alternately coating a chitosan solution and a hyaluronic acid solution with certain concentrations, so as to form a composite coating consisting of discontinuous single layers on the surface of the contact lens; the obtained contact lens with the hyaluronic acid-chitosan coating has high oxygen permeation rate, good antibacterial effect and moisturizing capacity, and has important significance.

Description

Technical Field

[0001] This invention relates to the field of contact lens surface coating technology, and more particularly to a preparation process of a hyaluronic acid-chitosan coating and contact lenses having a hyaluronic acid-chitosan coating. Background Technology

[0002] Compared to regular eyeglasses, contact lenses are increasingly popular due to their higher water content, softness, comfort, and convenience. Currently, the main materials used for contact lenses are hydrogel and silicone hydrogel. Hydrogel lenses are highly soft and elastic, blend well with tears, have low foreign body sensation, and offer excellent initial comfort. However, their oxygen permeability is relatively poor, and prolonged wear can easily cause corneal hypoxia. Silicone hydrogel lenses, on the other hand, have excellent oxygen permeability. The introduction of silicone creates molecular pores that allow direct oxygen transport, and their lower water content improves hydration, reducing dry eye problems and making them suitable for extended wear. However, their highly hydrophobic surface can easily attract protein deposits, potentially leading to inflammation.

[0003] Therefore, there is an urgent need for contact lenses that simultaneously possess moisturizing, antibacterial, and oxygen-permeable properties. Hyaluronic acid has a strong water-locking ability, and chitosan's natural antibacterial properties can reduce the risk of bacterial and microbial adhesion, thus reducing the probability of infections such as keratitis. Existing technology CN101987887A discloses a modified silicone rubber, specifically involving surface-treated silicone rubber followed by a silane reaction to imbue its surface with reactive chemical groups. This is then modified with chitosan and hyaluronic acid, combining their properties to obtain an antibacterial contact lens material with high moisturizing capabilities. However, while this method combines the properties of chitosan and hyaluronic acid, overcoming the technical problem of alternating coatings failing to maximize their properties, its moisturizing and antibacterial capabilities are insufficient. When the hyaluronic acid coating is on the outermost layer, its antibacterial performance is low, and when the chitosan coating is on the outermost layer, its moisturizing ability is poor. Furthermore, with prolonged use, the coating will peel off due to tear soaking and rinsing, significantly reducing its antibacterial effect and failing to meet usage requirements.

[0004] While the process of cross-linking chitosan and hyaluronic acid before coating ensures that both substances maximize their antibacterial and moisturizing effects, the high coating density reduces the oxygen permeability of the contact lens itself. This process places high demands on the oxygen permeability of the bare contact lens, and increased oxygen permeability inevitably leads to an increase in the silicone content of the lens, thus affecting the comfort of wearing the contact lens. Summary of the Invention

[0005] The purpose of this invention is to provide a preparation process for a hyaluronic acid-chitosan coating and a contact lens with a hyaluronic acid-chitosan coating, in order to solve the technical problem that existing contact lenses cannot simultaneously achieve long-lasting moisturizing, antibacterial effects and oxygen permeability.

[0006] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0007] This invention provides a process for preparing a hyaluronic acid-chitosan coating, comprising the following steps:

[0008] Step 1) After the bare contact lens is treated with plasma, a silane coupling agent solution is added for grafting treatment;

[0009] Step 2) Immerse the grafted contact lens in the first chitosan solution, the first hyaluronic acid solution, and the second chitosan solution in sequence;

[0010] Step 3) Immerse the soaked contact lens again in the second hyaluronic acid solution, and after washing, you will get contact lenses with a hyaluronic acid-chitosan coating;

[0011] The contact lens is made of silicone hydrogel material with an oxygen permeability ≥100Dk / t.

[0012] Furthermore, in step 1), the power of the plasma treatment is 60-80W, and the time is 30-120s;

[0013] The grafting treatment time is 20-40 minutes, and the grafting temperature is 32-37°C.

[0014] Furthermore, in step 1), the concentration of the silane coupling agent in the silane coupling agent solution is 1-3 wt%.

[0015] The silane coupling agent includes KH-550 silane coupling agent.

[0016] Furthermore, in step 2), the concentration of the first chitosan solution is 0.2–0.5 wt%, the concentration of the first hyaluronic acid solution is 0.3–0.6 wt%, and the concentration of the second chitosan solution is 0.4–0.7 wt%.

[0017] In the first chitosan solution and the second chitosan solution, the molecular weight of chitosan is 50-500 kDa;

[0018] In the first hyaluronic acid solution, the molecular weight of hyaluronic acid is 100-1000 kDa.

[0019] Furthermore, in step 2), the soaking time is independently 40 to 120 minutes, and the soaking temperature is 35 to 42°C.

[0020] Furthermore, in step 3), the concentration of hyaluronic acid in the second hyaluronic acid solution is 0.5–1.0 wt%.

[0021] The molecular weight of the hyaluronic acid is 100-1000 kDa.

[0022] Furthermore, in step 3), the soaking time with the second hyaluronic acid solution is 50-90 minutes, and the soaking temperature is 32-35℃.

[0023] Furthermore, the first hyaluronic acid solution and the second hyaluronic acid solution are obtained by mixing the hyaluronic acid solution with the EDC / NHS solution.

[0024] This invention provides a contact lens with a hyaluronic acid-chitosan coating prepared by the above-described preparation process.

[0025] Furthermore, the thickness of the hyaluronic acid-chitosan coating is 70–120 nm.

[0026] The beneficial effects of this invention are:

[0027] This invention discloses a preparation process for a hyaluronic acid-chitosan coating, wherein the coating is designed from the inside out as a chitosan coating, a hyaluronic acid coating, a chitosan coating, and a hyaluronic acid coating.

[0028] This invention achieves a low-density, discontinuous monolayer by alternating coating solutions of varying concentrations. Furthermore, the concentrations of the four solutions exhibit a gradient, resulting in a layer-by-layer variation in coating density. These alternating monolayers collectively constitute a multilayer composite three-dimensional coating. This multilayer composite approach preserves some of the microporous structure, allowing oxygen to permeate slowly. This minimizes the impact of dense cross-linking on the oxygen permeability of the silicone hydrogel lens, thus ensuring the oxygen permeability performance of the contact lens.

[0029] The three-dimensional topological structure of the composite coating maximizes the antibacterial effect of chitosan and the moisturizing ability of hyaluronic acid. The discontinuous single-layer design effectively avoids the technical problems that the antibacterial performance is not high when the hyaluronic acid coating is on the outermost side, and the moisturizing ability is poor when the chitosan coating is on the outermost side.

[0030] This invention utilizes plasma treatment and silane coupling agents to graft contact lens lenses, effectively improving the bonding strength between the chitosan layer and the lens, effectively avoiding the shortcomings of easy coating peeling, and significantly extending the service life of contact lenses. Detailed Implementation

[0031] This invention provides a process for preparing a hyaluronic acid-chitosan coating, comprising the following steps:

[0032] Step 1) After the bare contact lens is treated with plasma, a silane coupling agent solution is added for grafting treatment;

[0033] Step 2) Immerse the grafted contact lens in the first chitosan solution, the hyaluronic acid solution, and the second chitosan solution in sequence;

[0034] Step 3) Immerse the soaked contact lens again in the second hyaluronic acid solution, and after washing, you will get contact lenses with a hyaluronic acid-chitosan coating;

[0035] The contact lens is made of silicone hydrogel material with an oxygen permeability ≥100Dk / t.

[0036] In this invention, the oxygen permeability of the contact lens is preferably ≥120 Dk / t.

[0037] In this invention, the hyaluronic acid includes hyaluronic acid or its salts or chemical modifications thereof in forms acceptable for ocular use.

[0038] In this invention, the chitosan includes any ocularly acceptable form of chitosan or its chemical modifications thereof.

[0039] In this invention, in step 1), the power of the plasma treatment is 60-80W, preferably 70W; the time is 30-120s, preferably 40-100s, and more preferably 60s.

[0040] In this invention, in step 1), after plasma treatment, high-energy particles are generated by exciting gas ionization to clean the surface and introduce active groups on the surface of the bare contact lens, which facilitates the grafting of silane coupling agents.

[0041] In this invention, in step 1), the grafting treatment time is 20 to 40 minutes, preferably 30 minutes; the grafting treatment temperature is 32 to 37°C, preferably 35°C.

[0042] In this invention, in step 1), the concentration of the silane coupling agent in the silane coupling agent solution is 1-3 wt%, preferably 2 wt%.

[0043] The preferred silane coupling agent is KH-550 silane coupling agent.

[0044] In this invention, in step 2), the concentration of the first chitosan solution is 0.2-0.5 wt%, preferably 0.3 wt%; the concentration of the first hyaluronic acid solution is 0.3-0.6 wt%, preferably 0.4 wt%; and the concentration of the second chitosan solution is 0.4-0.7 wt%, preferably 0.5 wt%.

[0045] In the first chitosan solution and the second chitosan solution, the molecular weight of chitosan is 50-500 kD, preferably 100-300 kD, and more preferably 150 kD;

[0046] In the first hyaluronic acid solution, the molecular weight of hyaluronic acid is 100-1000 kD, preferably 200-800 kD, and more preferably 500 kD.

[0047] In this invention, as a preferred embodiment, in step 2), the concentration gradient of the first chitosan solution, the first hyaluronic acid solution, and the second chitosan solution changes, thereby avoiding the risk of a significant decrease in the oxygen permeability of contact lenses caused by the dense surface coating clogging the pores of the silicone hydrogel.

[0048] In this invention, in step 2), the soaking time is independently 40 to 120 minutes, preferably 60 to 100 minutes, and more preferably 80 minutes; the soaking temperature is 35 to 42°C, preferably 38°C.

[0049] In this invention, in step 3), the concentration of hyaluronic acid in the second hyaluronic acid solution is 0.5-1 wt%, preferably 0.8 wt%.

[0050] The hyaluronic acid has a molecular weight of 100-1000 kD, preferably 200-800 kD, and more preferably 500 kD.

[0051] In this invention, in step 3), the soaking time with the second hyaluronic acid solution is 50-90 minutes, preferably 60-80 minutes, and more preferably 70 minutes; the soaking temperature is 32-35°C, preferably 33°C.

[0052] In this invention, the first hyaluronic acid solution and the second hyaluronic acid solution are obtained by mixing the hyaluronic acid solution with the EDC / NHS solution.

[0053] In this invention, the first hyaluronic acid solution and the second hyaluronic acid solution are prepared by mixing the hyaluronic acid solution with the EDC / NHS solution according to the molar ratio of EDC, NHS and hyaluronic acid carboxyl groups of 1 to 3:1 to 3:1.

[0054] In this invention, the EDC / NHS solution is an N-hydroxysuccinimide / 1-ethyl-(3-dimethylaminopropyl)carbodiimide solution.

[0055] In this invention, after the bare contact lens is soaked in the first hyaluronic acid solution and the second hyaluronic acid solution, it needs to be washed with deionized water 3 to 5 times and then dried with nitrogen.

[0056] This invention provides a contact lens with a hyaluronic acid-chitosan coating prepared by the above-described preparation process.

[0057] In this invention, the thickness of the hyaluronic acid-chitosan coating is 70-120 nm, preferably 80-110 nm, and more preferably 100 nm.

[0058] In this invention, the EDC / NHS solution is obtained by mixing equal volumes of EDC aqueous solution and NHS aqueous solution, wherein the concentrations of the EDC aqueous solution and NHS aqueous solution are 0.1M, and both EDC and NHS are purchased from Shanghai Sangon Biotech Co., Ltd.

[0059] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0060] Example 1

[0061] Chitosan with a molecular weight of 80 kD was dissolved in water to obtain a first chitosan solution with a concentration of 0.5 wt%; chitosan with a molecular weight of 300 kD was dissolved in water to obtain a second chitosan solution with a concentration of 0.5 wt%.

[0062] Contact lens nudes with an oxygen permeability of 150 Dk / t were plasma-treated at 70 W for 70 s, then immersed in an ethanol solution of 2 wt% 3-aminopropyltrimethoxysilane at 35 °C for 30 min, washed three times with anhydrous ethanol, and then immersed in a first chitosan solution for 40 min and washed three times with water.

[0063] Based on the number of carboxyl groups in hyaluronic acid, and with a molar ratio of EDC, NHS, and hyaluronic acid carboxyl groups of 2:2:1, a hyaluronic acid aqueous solution with a molecular weight of 100kD was prepared with a concentration of 2mM. This solution was then mixed with the EDC / NHS solution to obtain a first hyaluronic acid solution with a concentration of 0.4wt%. The bare contact lenses were then soaked in the hyaluronic acid solution for 40 minutes, washed with water three times, dried with nitrogen, and then soaked again in a second chitosan solution for 50 minutes. After that, they were removed, washed with water twice, and then put into use.

[0064] A 2mM hyaluronic acid aqueous solution was prepared using hyaluronic acid with a molecular weight of 500kD, in a molar ratio of EDC, NHS, and hyaluronic acid carboxyl groups of 1:1:1. This solution was then mixed with the EDC / NHS solution to obtain a second hyaluronic acid solution with a concentration of 0.8wt%. The bare contact lens was immersed in the second hyaluronic acid solution for 50 minutes, then removed, washed four times with water, and dried with nitrogen to obtain a contact lens with a hyaluronic acid-chitosan coating. The oxygen permeability was 127Dk / t, the thickness of the hyaluronic acid-chitosan coating was 107nm, and the contact angle was 15.88°.

[0065] Example 2

[0066] Unlike Example 1, in this example, the chitosan molecular weight of the first chitosan solution is 100kD, the concentration of the first chitosan solution is 0.3wt%, the concentration of the second chitosan solution with a molecular weight of 200kD is 0.5wt%, the concentration of the first hyaluronic acid solution is 0.4wt%, and the concentration of the second hyaluronic acid solution is 0.6wt%. The resulting contact lens with a hyaluronic acid-chitosan coating has an oxygen permeability of 132Dk / t, a thickness of 96nm, and a contact angle of 17.15°.

[0067] Example 3

[0068] Unlike Example 1, in this example, the molecular weight of chitosan in the first chitosan solution is 400 kD, the molecular weight of chitosan in the second chitosan solution is 400 kD, the molecular weight of hyaluronic acid in the first hyaluronic acid solution is 200 kD, and the molecular weight of hyaluronic acid in the second hyaluronic acid solution is 500 kD. The resulting contact lens with a hyaluronic acid-chitosan coating has an oxygen permeability of 115 Dk / t, a coating thickness of 112 nm, and a contact angle of 16.21°.

[0069] Comparative Example 1

[0070] Unlike Example 1, in this comparative example, only a 1 wt% chitosan solution and a 1 wt% hyaluronic acid solution were used to sequentially coat the bare contact lens. The resulting contact lens with a hyaluronic acid-chitosan coating had an oxygen permeability of 104 Dk / t, a coating thickness of 86 nm, and a contact angle of 14.2°.

[0071] Comparative Example 2

[0072] Unlike Example 1, in this comparative example, only a 1 wt% hyaluronic acid solution and a 1 wt% chitosan solution were used to sequentially coat the bare contact lens. The resulting contact lens with the hyaluronic acid-chitosan coating had an oxygen permeability of 102 Dk / t, a coating thickness of 88 nm, and a contact angle of 18.5°.

[0073] Comparative Example 3

[0074] Unlike Example 1, in this comparative example, the first hyaluronic acid and the first chitosan solution were mixed and a cross-linking reaction was carried out. Then, the bare contact lens was immersed in the mixture for 40 minutes. After washing and drying, a contact lens with a hyaluronic acid-chitosan coating was obtained, with an oxygen permeability of 76 Dk / t and a thickness of 56 nm.

[0075] Contact lenses with hyaluronic acid-chitosan coatings prepared in Examples 1-3 and Comparative Examples 1-3, as well as blank silicone hydrogel contact lenses, were used. *Escherichia coli* and *Staphylococcus aureus* were inoculated onto the contact lenses, respectively. A sterile filter membrane was then placed on each lens, and the lenses were incubated at 37°C with saturated humidity for 18 hours. After removing the sterile filter membrane, the bacterial count was determined using the plate count method, and a parallel comparison was performed with unmodified PDMS (blank sample). The antibacterial effect was determined by calculating the inhibition rate. The antibacterial rate was calculated using the formula: R(%) = (BC) / B × 100%. In the formula: R is the inhibition rate (%), B is the average number of recovered colonies (cfu / lens) in the blank control sample, and C is the average number of recovered colonies (cfu / lens) in the sample.

[0076] Table 1 shows the characterization data of oxygen permeability, contact angle, coating thickness, and antibacterial rate of contact lenses with hyaluronic acid-chitosan coatings obtained in Examples 1-3 and Comparative Examples 1-3.

[0077] Table 1. Characterization data of oxygen permeability, contact angle, coating thickness, and antibacterial rate of contact lenses with hyaluronic acid-chitosan coatings obtained in Examples 1-3 and Comparative Examples 1-3.

[0078]

[0079]

[0080] As can be seen from the above embodiments, the present invention provides a preparation process for a hyaluronic acid-chitosan coating and a contact lens with a hyaluronic acid-chitosan coating. As shown in Table 1, Examples 1-3, by alternately coating with low-concentration chitosan solution and hyaluronic acid solution, form a multi-layered structure on the surface of the bare contact lens, resulting in a discontinuous single-layer composite structure that not only has dual moisturizing capabilities but also excellent oxygen permeability. Comparative Examples 1 and 2 prepared surface coatings by alternating application of chitosan and hyaluronic acid, respectively. Based on the requirements of target antibacterial rate and moisturizing properties, the concentrations of the chitosan and hyaluronic acid solutions were slightly increased compared to Examples 1 and 3. However, both antibacterial effect and water content could not be simultaneously achieved. Comparative Example 3 involved cross-linking chitosan and hyaluronic acid before coating the contact lens surface. Although both chitosan and hyaluronic acid are hydrophilic substances, their dense cross-linking resulted in a three-dimensional network structure, which partially encapsulated the hydrophilic groups, slightly reducing the surface energy and consequently slightly increasing the contact angle. Simultaneously, the dense coating covered the pores in the silicone hydrogel, significantly reducing oxygen permeability. Therefore, the present invention has a simple process, low cost, and yields contact lenses with a hyaluronic acid-chitosan coating that combine long-lasting moisturizing, antibacterial effects, and oxygen permeability, which is of significant importance.

[0081] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A preparation process for a hyaluronic acid-chitosan coating, characterized in that, Includes the following steps: Step 1) After the bare contact lens is treated with plasma, a silane coupling agent solution is added for grafting treatment; Step 2) Immerse the grafted contact lens in the first chitosan solution, the first hyaluronic acid solution, and the second chitosan solution in sequence; Step 3) Immerse the soaked contact lens again in the second hyaluronic acid solution, and after washing, you will get contact lenses with a hyaluronic acid-chitosan coating; The contact lens is made of silicone hydrogel material with an oxygen permeability ≥100Dk / t.

2. The preparation process of the hyaluronic acid-chitosan coating according to claim 1, characterized in that, In step 1), the power of the plasma treatment is 60-80W, and the time is 30-120s; The grafting treatment time is 20-40 minutes, and the grafting temperature is 32-37°C.

3. The preparation process of a hyaluronic acid-chitosan coating according to claim 1 or 2, characterized in that, In step 1), the concentration of the silane coupling agent in the silane coupling agent solution is 1-3 wt%. The silane coupling agent includes KH-550 silane coupling agent.

4. The preparation process of the hyaluronic acid-chitosan coating according to claim 3, characterized in that, In step 2), the concentration of the first chitosan solution is 0.2-0.5 wt%, the concentration of the first hyaluronic acid solution is 0.3-0.6 wt%, and the concentration of the second chitosan solution is 0.4-0.7 wt%. In the first chitosan solution and the second chitosan solution, the molecular weight of chitosan is 50-500 kDa; In the first hyaluronic acid solution, the molecular weight of hyaluronic acid is 100-1000 kDa.

5. The preparation process of a hyaluronic acid-chitosan coating according to claim 1, 2, or 4, characterized in that, In step 2), the soaking time is 40 to 120 minutes and the soaking temperature is 35 to 42°C.

6. The preparation process of a hyaluronic acid-chitosan coating according to claim 1 or 2, characterized in that, In step 3), the concentration of hyaluronic acid in the second hyaluronic acid solution is 0.5–1.0 wt%. The molecular weight of the hyaluronic acid is 100-1000 kDa.

7. The preparation process of the hyaluronic acid-chitosan coating according to claim 1, characterized in that, In step 3), the soaking time with the second hyaluronic acid solution is 50-90 minutes, and the soaking temperature is 32-35℃.

8. The preparation process of the hyaluronic acid-chitosan coating according to claim 1, characterized in that, The first hyaluronic acid solution and the second hyaluronic acid solution are obtained by mixing the hyaluronic acid solution with the EDC / NHS solution.

9. Contact lenses with a hyaluronic acid-chitosan coating prepared by the preparation process according to any one of claims 1 to 8.

10. A contact lens with a hyaluronic acid-chitosan coating according to claim 9, characterized in that, The thickness of the hyaluronic acid-chitosan coating is 70–120 nm.

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