A contact lens lubricant containing lysozyme and recombinant collagen, its preparation method and application.

Abstract

This invention provides a contact lens lubricant containing lysozyme and recombinant collagen, its preparation method, and its application, belonging to the technical field of eye care products. The contact lens lubricant provided by this invention comprises the following components: 0.01%–0.5% lysozyme, 0.1%–2.0% recombinant collagen, 0.5%–1.2% osmotic pressure regulator, 0.01%–0.1% viscosity regulator, and 0.1%–2.0% pH buffer. This invention uses lysozyme and recombinant collagen as the core active ingredients; their synergistic effect provides antibacterial, moisturizing, corneal repair, and improved wearing comfort functions. This invention also provides a method for preparing the above-mentioned contact lens lubricant and its application in the preparation of products for relieving dry eye syndrome and preventing contact lens-related keratitis.

Description

Technical Field

[0001] This invention belongs to the field of eye care product technology, specifically relating to a contact lens lubricant containing lysozyme and recombinant collagen, its preparation method, and its application. Background Technology

[0002] Contact lenses play a vital role in improving visual health due to their optical correction advantages. Their comfort and convenience have made them popular among nearsighted individuals, leading to a continuous increase in the number of wearers in recent years. However, dry eyes are a common problem when wearing contact lenses. This not only causes deposits to accumulate on the lens surface, leading to decreased vision, reduced oxygen permeability, and even changes in lens size, severely impacting the quality of lens wear, but also significantly reducing comfort. Consequently, contact lens lubricants have emerged to alleviate dryness and friction during contact lens wear and maintain lens surface moisture. However, most contact lens lubricants currently on the market rely on moisturizers such as hyaluronic acid and hydroxypropyl methylcellulose. While they can alleviate dry eyes to some extent, they mostly only provide simple lubrication and hydration, offering limited functionality and having limited impact on improving the ocular microenvironment and promoting ocular tissue repair. Furthermore, they often rely on preservatives (such as benzalkonium chloride) to maintain sterility, potentially increasing the risk of non-compliance with biocompatibility requirements. Long-term use may cause eye irritation or allergic reactions.

[0003] Lysozyme is a natural antibacterial protein with wide applications in the medical and food industries. It hydrolyzes peptidoglycans in bacterial cell walls, exhibiting bactericidal effects while maintaining high safety, making it a viable alternative to chemical preservatives. Recombinant collagen is a novel material developed using protein engineering and gene recombination technology, possessing advantages such as no viral risks, low rejection rates, and good water solubility. While there are reports of using lysozyme or recombinant collagen in ophthalmic preparations, the key challenge in this field is how to rationally combine these two components and optimize the formulation to achieve a synergistic effect in contact lens lubricants. The goal is to create contact lens lubricants that effectively inhibit microbial growth, promote corneal epithelial repair, and possess excellent lubrication and moisturizing properties while being low in irritation. Summary of the Invention

[0004] In order to solve the problems existing in the prior art, the purpose of this invention is to provide a contact lens lubricant containing lysozyme and recombinant collagen and its preparation method. With lysozyme and recombinant collagen as the core active ingredients, the two work synergistically to have the functions of antibacterial, moisturizing, corneal repair and improved wearing comfort.

[0005] The present invention also aims to provide the application of the above-mentioned contact lens lubricant in the preparation of products for relieving dry eye and preventing contact lens-related keratitis.

[0006] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0007] This invention provides a contact lens lubricant containing lysozyme and recombinant collagen, comprising the following components by weight and volume percentage: 0.01% to 0.5% lysozyme, 0.1% to 2.0% recombinant collagen, 0.5% to 1.2% osmotic pressure regulator, 0.01% to 0.1% viscosity regulator, and 0.1% to 2.0% pH buffer.

[0008] Preferably, the contact lens lubricant does not contain chemical preservatives.

[0009] Preferably, the osmotic pressure regulator comprises sodium chloride and / or glycerol.

[0010] Preferably, the viscosity modifier comprises hydroxypropyl methylcellulose and / or sodium carboxymethyl cellulose.

[0011] Preferably, the pH buffer comprises a borate-borax buffer and / or a phosphate buffer.

[0012] The present invention also provides a method for preparing the above-mentioned contact lens lubricant, comprising the following steps: dissolving a buffer and an osmotic pressure regulator in deionized water and stirring until clear to obtain component A; adding lysozyme to component A, stirring at low temperature to dissolve, then adding recombinant collagen and hydrating at high temperature to obtain component B; adding a viscosity regulator to component B, mixing and sterilizing to obtain the contact lens lubricant.

[0013] Preferably, the temperature of the low-temperature stirring is 2 to 8°C.

[0014] Preferably, the temperature is increased to 25-30°C.

[0015] Preferably, the sterilization is performed by filtration through a 0.22 μm filter membrane.

[0016] The present invention also provides the application of the above-mentioned contact lens lubricant in the preparation of products for relieving dry eye and preventing contact lens-related keratitis.

[0017] Compared with the prior art, the beneficial effects of the technical solution of the present invention are as follows:

[0018] The contact lens lubricant provided by this invention uses lysozyme and recombinant collagen as its core components. Lysozyme inhibits bacterial growth, while recombinant collagen forms a hydrophilic film on the lens surface, reducing friction and repairing micro-damage. The two work synergistically to provide antibacterial, moisturizing, corneal repair, and improved wearing comfort functions. Furthermore, this contact lens lubricant has low irritation and a low risk of eye infection, making it suitable for sensitive individuals. Detailed Implementation

[0019] This invention provides a contact lens lubricant containing lysozyme and recombinant collagen, comprising the following components by weight-volume percentage: lysozyme 0.01%–0.5%, recombinant collagen 0.1%–2.0%, osmotic pressure regulator 0.5%–1.2%, viscosity regulator 0.01%–0.1%, and pH buffer 0.1%–2.0%. Preferably, the contact lens lubricant comprises the following components: lysozyme 0.1%–0.3%, recombinant collagen 0.5%–1.2%, osmotic pressure regulator 0.6%–1.0%, viscosity regulator 0.05%–0.08%, and pH buffer 0.15%–0.5%. The unit of weight-volume ratios in this invention is g / mL. The contact lens lubricant of this invention also includes deionized water, preferably supplemented by deionized water to maintain the balance of the components.

[0020] The contact lens lubricant of this invention is free of chemical preservatives. The added lysozyme provides broad-spectrum antibacterial activity, replacing traditional preservatives. The contact lens lubricant of this invention has an inhibition rate of >99.9% against Staphylococcus aureus. The recombinant collagen in the contact lens lubricant of this invention can form a hydrophilic film on the lens surface, promoting corneal repair, reducing damage caused by mechanical friction, and working synergistically with lysozyme to provide antibacterial, moisturizing, corneal repair, and improved wearing comfort functions. The moisturizing time of the contact lens lubricant of this invention is 40% longer than that of traditional hyaluronic acid formulas. Furthermore, the contact lens lubricant of this invention is non-irritating, with a Draize score ≤1, making it suitable for sensitive individuals. This invention does not limit the source of lysozyme and recombinant collagen; conventional commercially available products are acceptable.

[0021] The osmotic pressure regulator of this invention includes sodium chloride and / or glycerin. By adding the osmotic pressure regulator, this invention can adjust the contact lens lubricant to be isotonic with tears (280-320 mOsm / kg). The viscosity regulator of this invention includes hydroxypropyl methylcellulose and / or sodium carboxymethyl cellulose. By adding the viscosity regulator, this invention can prolong the wetting time. The pH buffer of this invention includes borate-borax buffer and / or phosphate buffer. By adding the pH buffer, this invention can adjust the pH of the contact lens lubricant to 6.5-7.5.

[0022] The present invention also provides a method for preparing the above-mentioned contact lens lubricant, comprising the following steps: dissolving a buffer and an osmotic pressure regulator in deionized water and stirring until clear to obtain component A; adding lysozyme to component A, stirring at low temperature to dissolve, then adding recombinant collagen and hydrating at high temperature to obtain component B; adding a viscosity regulator to component B, mixing and sterilizing to obtain the contact lens lubricant.

[0023] The low-temperature stirring temperature described in this invention is 2–8°C, optionally 3°C, 4°C, 5°C, 6°C, or 7°C. This invention dissolves lysozyme through low-temperature stirring, avoiding its inactivation. The heating temperature described in this application is 25–30°C, optionally 26°C, 27°C, 28°C, or 29°C. That is, after adding recombinant collagen, the temperature is slowly increased to ensure full hydration. Hydration in this invention refers to the process of water separation (also known as hydration). The slow heating rate is preferably 0.1–0.5°C / min. This invention ensures the activity of lysozyme and collagen by controlling pH and using a low-temperature preparation process, thus guaranteeing their antibacterial, moisturizing, and corneal repair effects.

[0024] The sterilization method described in this invention is preferably sterilization using a 0.22μm filter membrane. Alternatively, this invention can be used to aseptically package the sterilized contact lens lubricant to obtain the final product.

[0025] The present invention also provides the application of the above-mentioned contact lens lubricant in the preparation of products for relieving dry eye and preventing contact lens-related keratitis, wherein the products preferably contain 50-100 wt% of the contact lens lubricant described in the present invention.

[0026] The technical solutions of this invention will be clearly and completely described below with reference to the embodiments thereof. Obviously, the described embodiments are only a part of the embodiments of this invention, and not all of them. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without creative effort are within the scope of protection of this invention.

[0027] In a specific embodiment of the present invention, lysozyme (Sigma), production batch number WXBF2947V; and recombinant collagen were purchased from Jiangsu Chuangjian Medical Technology Co., Ltd., production batch number F2410003.

[0028] Unless otherwise specified, the following embodiments are all conventional methods.

[0029] Unless otherwise specified, all materials and reagents used in the following examples are commercially available.

[0030] Example 1

[0031] A contact lens lubricant containing lysozyme and recombinant collagen, comprising the following components by weight-volume percentage (g / mL): 0.01% lysozyme, 0.1% recombinant collagen, 0.5% osmotic pressure regulator (glycerol), 0.01% viscosity regulator (sodium carboxymethyl cellulose), and 0.1% pH buffer (boric acid-borax buffer, pH 7.0).

[0032] Preparation method steps: Dissolve the buffer and osmotic pressure regulator in deionized water and stir until clear to obtain component A; add lysozyme to component A and stir to dissolve at 2℃, then add recombinant collagen and heat to 25℃ at 0.1℃ / min to fully hydrate it to obtain component B; add viscosity regulator to component B, mix and sterilize to obtain contact lens lubricant.

[0033] Example 2

[0034] A contact lens lubricant containing lysozyme and recombinant collagen, comprising the following components by weight-volume percentage (g / mL): lysozyme 0.5%, recombinant collagen 2.0%, osmotic pressure regulator (sodium chloride) 1.2%, viscosity regulator (hydroxypropyl methylcellulose) 0.1%, and pH buffer (phosphate buffer, pH 6.8) 2%.

[0035] Preparation method steps: Dissolve the buffer and osmotic pressure regulator in deionized water and stir until clear to obtain component A; add lysozyme to component A and stir to dissolve at 8°C, then add recombinant collagen and heat to 30°C at 0.5°C / min to fully hydrate it to obtain component B; add viscosity regulator to component B, mix and sterilize to obtain contact lens lubricant.

[0036] Example 3

[0037] A contact lens lubricant containing lysozyme and recombinant collagen, comprising the following components by weight-volume percentage (g / mL): lysozyme 0.2%, recombinant collagen 0.8%, osmotic pressure regulator (sodium chloride) 0.9%, viscosity regulator (sodium carboxymethyl cellulose) 0.05%, and pH buffer (boric acid-borax buffer, pH 7.0) 0.8%.

[0038] Preparation method steps: Dissolve the buffer and osmotic pressure regulator in deionized water and stir until clear to obtain component A; add lysozyme to component A and stir to dissolve at 4℃, then add recombinant collagen and heat to 28℃ at 0.2℃ / min to fully hydrate it to obtain component B; add viscosity regulator to component B, mix and sterilize to obtain contact lens lubricant.

[0039] Example 4

[0040] A contact lens lubricant containing lysozyme and recombinant collagen, comprising the following components by weight-volume percentage (g / mL): lysozyme 0.3%, recombinant collagen 1.0%, osmotic pressure regulator (glycerol) 1.0%, viscosity regulator (hydroxypropyl methylcellulose) 0.03%, and pH buffer (phosphate buffer, pH 6.8) 1.2%.

[0041] Preparation method steps: Dissolve the buffer and osmotic pressure regulator in deionized water and stir until clear to obtain component A; add lysozyme to component A and stir to dissolve at 4℃, then add recombinant collagen and heat to 26℃ at 0.3℃ / min to fully hydrate it to obtain component B; add viscosity regulator to component B, mix and sterilize to obtain contact lens lubricant.

[0042] Comparative Example 1

[0043] Compared to Example 3, the addition of lysozyme and recombinant collagen was omitted (double negative control group):

[0044] The product comprises the following components by mass-volume percentage (g / mL): 0.9% osmotic pressure regulator (sodium chloride), 0.05% viscosity regulator (sodium carboxymethyl cellulose), and 0.8% pH buffer (boric acid-borax buffer, pH 7.0).

[0045] Preparation method steps: Dissolve the buffer and osmotic pressure regulator in deionized water, stir until clear, and obtain component A; add viscosity regulator to component A, mix and sterilize.

[0046] Comparative Example 2

[0047] Compared to Example 4, the addition of lysozyme and recombinant collagen was omitted (double negative control group):

[0048] By mass-volume percentage (g / mL), it comprises the following components: osmotic pressure regulator (glycerol) 1.0%, viscosity regulator (hydroxypropyl methylcellulose) 0.03%, and pH buffer (phosphate buffer, pH 6.8) 1.2%.

[0049] Preparation method steps: Dissolve the buffer and osmotic pressure regulator in deionized water, stir until clear, and obtain component A; add viscosity regulator to component A, mix and sterilize to obtain contact lens lubricant.

[0050] Comparative Example 3

[0051] Compared to Example 3, the addition of lysozyme was omitted (lysozyme negative control):

[0052] By mass-volume percentage (g / mL), it comprises the following components: 0.8% recombinant collagen, 0.9% osmotic pressure regulator (sodium chloride), 0.05% viscosity regulator (sodium carboxymethyl cellulose), and 0.8% pH buffer (boric acid-borax buffer, pH 7.0).

[0053] Preparation method steps: Dissolve the buffer and osmotic pressure regulator in deionized water and stir until clear to obtain component A; add recombinant collagen to component A and heat to 28℃ at 0.2℃ / min to fully hydrate it to obtain component B; add viscosity regulator to component B, mix and sterilize to obtain contact lens lubricant.

[0054] Comparative Example 4

[0055] Compared to Example 4, the addition of lysozyme was omitted (lysozyme negative control):

[0056] By mass-volume percentage (g / mL), it comprises the following components: 1.0% recombinant collagen, 1.0% osmotic pressure regulator (glycerol), 0.03% viscosity regulator (hydroxypropyl methylcellulose), and 1.2% pH buffer (phosphate buffer, pH 6.8).

[0057] Preparation method steps: Dissolve the buffer and osmotic pressure regulator in deionized water and stir until clear to obtain component A; add recombinant collagen to component A and heat to 26℃ at 0.3℃ / min to fully hydrate it to obtain component B; add viscosity regulator to component B, mix and sterilize to obtain contact lens lubricant.

[0058] Comparative Example 5

[0059] Compared to Example 3, the addition of recombinant collagen was omitted (recombinant collagen negative control):

[0060] By mass-volume percentage (g / mL), it comprises the following components: lysozyme 0.2%, osmotic pressure regulator (sodium chloride) 0.9%, viscosity regulator (sodium carboxymethyl cellulose) 0.05%, and pH buffer (boric acid-borax buffer, pH 7.0) 0.8%.

[0061] Preparation method steps: Dissolve the buffer and osmotic pressure regulator in deionized water and stir until clear to obtain component A; add lysozyme to component A and stir to dissolve at 4°C to obtain component B; add viscosity regulator to component B, mix and sterilize to obtain contact lens lubricant.

[0062] Comparative Example 6

[0063] Compared to Example 4, the addition of recombinant collagen was omitted (recombinant collagen negative control):

[0064] By mass-volume percentage (g / mL), it comprises the following components: lysozyme 0.3%, osmotic pressure regulator (glycerol) 1.0%, viscosity regulator (hydroxypropyl methylcellulose) 0.03%, and pH buffer (phosphate buffer, pH 6.8) 1.2%.

[0065] Preparation method steps: Dissolve the buffer and osmotic pressure regulator in deionized water and stir until clear to obtain component A; add lysozyme to component A and stir to dissolve at 4°C to obtain component B; add viscosity regulator to component B, mix and sterilize to obtain contact lens lubricant.

[0066] Experimental Example 1

[0067] The following experiments were conducted using Examples 3-4 and Comparative Examples 1-6, with existing products serving as controls:

[0068] (1) Antibacterial test: The test method was in accordance with YY / T0719.3-20090719 (24 hours). The conventional lubricant containing biguanide preservative was a brand of Shanghai Weikang Optical Glasses Co., Ltd., with the trade name Weikangmei. The test results are as follows:

[0069] Table 1. Results of antibacterial test

[0070]

[0071] The results showed that the contact lens lubricant containing lysozyme and recombinant collagen provided by this invention has good antibacterial properties against Staphylococcus aureus ATCC6538, Pseudomonas aeruginosa ATCC9027, Escherichia coli ATCC8739, Candida albicans ATCC10231, and Fusarium oxysporum ATCC36031. Its antibacterial effect is comparable to or slightly higher than that of commercially available lubricants containing biguanide preservatives. The antibacterial effect decreased after omitting the addition of recombinant collagen, and the antibacterial effect decreased significantly after omitting the addition of lysozyme. At the same time, the antibacterial effect was very poor after omitting both recombinant collagen and lysozyme.

[0072] (2) Lubricity Test: The test method was in accordance with GB / T 10006-2021 (friction material: float glass; worn material: white silicone). The commercially available sodium hyaluronate-containing lubricant was a brand of Shanghai Weikang Optical Glasses Co., Ltd., with the product name Weikang Mei. The test results are as follows:

[0073] Table 2 Lubricity test results

[0074]

[0075]

[0076] The results showed that the contact lens lubricant containing lysozyme and recombinant collagen provided by the present invention has good lubricity, which is better than that of commercially available lubricants containing sodium hyaluronate. The lubrication effect decreased significantly after the addition of recombinant collagen was omitted, and the lubrication effect also decreased after the addition of lysozyme was omitted. At the same time, the lubrication effect was poor after omitting both recombinant collagen and lysozyme, and was close to that of physiological saline.

[0077] 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 contact lens lubricating solution comprising lysozyme and recombinant collagen, characterized in that, The lysozyme is 0.01% to 0.5% by mass, the recombinant collagen is 0.1% to 2.0% by mass, the osmotic pressure regulator is 0.5% to 1.2% by mass, the viscosity regulator is 0.01% to 0.1% by mass, and the pH buffer is 0.1% to 2.0% by mass; The osmotic pressure regulator comprises sodium chloride and / or glycerol; The viscosity regulator comprises hydroxypropyl methyl cellulose and / or sodium carboxymethyl cellulose; The pH buffer comprises a boric acid-borax buffer and / or a phosphate buffer; The preparation method of the contact lens lubricant comprises the following steps: dissolving the buffer and the osmotic pressure regulator in deionized water, stirring to clarify, and obtaining component A; adding the lysozyme to component A, stirring to dissolve at low temperature, then adding the recombinant collagen, and hydrating at elevated temperature to obtain component B; adding the viscosity regulator to component B, mixing, and filtering to sterilize to obtain the contact lens lubricant; the temperature of the low-temperature stirring is 2 to 8°C; the elevated temperature is 25 to 30°C; and the sterilization is 0.22 μm filter membrane sterilization.

2. The contact lens lubricating liquid of claim 1, wherein The contact lens lubricant does not contain a chemical preservative.

3. Use of the contact lens lubricant according to any one of claims 1 to 2 in the preparation of a product for relieving dry eye and preventing contact lens-related keratitis.

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