Antibacterial multifunctional eye-moistening liquid for contact lenses and preparation method of antibacterial multifunctional eye-moistening liquid

Abstract

The invention provides antibacterial multifunctional eye moistening liquid for contact lenses and a preparation method of the antibacterial multifunctional eye moistening liquid, and belongs to the technical field of ophthalmic liquid medicine. The invention discloses an anti-freezing agent which is prepared from the following components in percentage by mass: 0.05 to 0.15 percent of epsilon-polylysine, 0.01 to 0.04 percent of epsilon-polylysine zinc, 0.1 to 0.5 percent of poloxamer, 1 to 3 percent of trehalose, 0.1 to 0.3 percent of cocamidopropyl betaine, 0.4 to 1 percent of glycerol, 0.01 to 0.05 percent of disodium magnesium ethylene diamine tetraacetate and the balance of water. Trehalose and glycerol can lubricate and replenish water instantly and have a synergistic effect, so that the dry and astringent feeling of wearing glasses can be effectively relieved; the epsilon-polylysine and the zinc salt thereof synergistically improve the bactericidal performance and enhance the stability of the system. The eye lotion obtained by the invention has the technical effects of high biological safety, antibacterial property and high moisture retention.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of ophthalmic solutions, in particular to an antibacterial multifunctional contact lens eye drop and a preparation method thereof. BACKGROUND

[0002] Contact lenses can accelerate tear evaporation, leading to corneal dehydration, and a dry environment can easily cause corneal damage or inflammation. Dry eyes can cause the lens to dehydrate and harden, affecting light transmission and wearing stability. Eye drops containing hyaluronic acid and other moisturizing ingredients can instantly replenish tears, relieve dryness, foreign body sensation, and fatigue. Especially for people who use their eyes for a long time (such as computer work) or have insufficient tear secretion, it is a key auxiliary product to maintain comfortable wearing.

[0003] Existing contact lens eye drops often contain preservatives and antibiotic ingredients. The main role of preservatives is to extend the shelf life of eye drops and prevent the growth of microorganisms. However, the addition of preservatives can cause direct irritation to the eye surface. Long-term use of eye drops containing preservatives can cause damage to corneal epithelial cells and even cause corneal inflammation, manifesting as redness, pain, or photophobia in the eyes.

[0004] The prior art with publication number CN119101572A uses catechin and ginkgo flavones as bacteriostatic ingredients, which are relatively safe and have mild product efficacy, but have limited bacteriostatic properties and unsatisfactory moisturizing effect. Therefore, it is of great significance to provide a contact lens eye drop with higher safety, moisturizing, cleaning, and antibacterial effects. SUMMARY

[0005] The purpose of the present application is to provide an antibacterial multifunctional contact lens eye drop and a preparation method thereof, which solves the technical problems of high irritation, insufficient biological safety, and single function of existing eye drops.

[0006] In order to achieve the above-mentioned purpose of the application, the following technical solutions are provided:

[0007] The present application provides an antibacterial multifunctional contact lens eye drop, which is composed of the following components by mass fraction: 0.05-0.15% of epsilon-polylysine, 0.01-0.04% of zinc epsilon-polylysine, 0.1-0.5% of poloxamer, 1-2% of trehalose, 0.1-0.3% of cocamidopropyl betaine, 0.4-1% of glycerol, 0.01-0.05% of disodium magnesium ethylenediaminetetraacetate, and the balance is water.

[0008] Further, the pH of the antibacterial multifunctional contact lens eye drop is 6.8-7.2.

[0009] Further, the pH of the antibacterial multifunctional contact lens eye drop is adjusted by using Tris base and dilute hydrochloric acid solution as a pH adjuster.

[0010] Furthermore, the poloxamer includes poloxamer 184.

[0011] This invention also provides a method for preparing an antibacterial multifunctional eye drop for contact lenses. Under stirring conditions, Tris base is first dissolved in water, then disodium magnesium ethylenediaminetetraacetate is added, the pH of the system is adjusted with dilute hydrochloric acid solution, and finally the remaining raw materials are dissolved in water one by one, followed by volume adjustment, filtration, and sterilization.

[0012] Furthermore, the stirring temperature is 40–50°C, and the stirring speed is 50–200 rpm.

[0013] Furthermore, the ε-polylysine zinc is added in the form of a dispersion;

[0014] The mass ratio of ε-polylysine zinc to water in the ε-polylysine zinc dispersion is 0.05–0.15:3–20.

[0015] Furthermore, the ε-polylysine zinc dispersion is obtained by adding ε-polylysine zinc into water under high-speed stirring.

[0016] Furthermore, the high-speed stirring speed is 800-2500 rpm, and the high-speed stirring time is sufficient to fully disperse ε-polylysine zinc.

[0017] The beneficial effects of this invention are:

[0018] The eye drops obtained by this invention have multiple effects such as antibacterial and moisturizing, are non-irritating, preservative-free, and biosafe. Trehalose can form a stable hydration film on the lens surface, providing long-lasting moisturization; glycerin provides immediate lubrication and hydration, and the two work synergistically to effectively relieve the dryness of wearing contact lenses. ε-polylysine and ε-polylysine zinc are used to replace traditional chemical preservatives, which greatly reduces the risk of ocular surface cell damage and allergic reactions caused by preservatives. ε-polylysine is a natural cationic antimicrobial peptide that exerts a bactericidal effect by disrupting the cell membrane of microorganisms. Its zinc salt form (ε-polylysine zinc) enhances its stability and antibacterial efficacy, and zinc ions themselves also have auxiliary antibacterial and wound-healing effects. Detailed Implementation

[0019] This invention provides an antibacterial multifunctional eye drops for contact lenses, comprising the following components by mass fraction: 0.05-0.15% ε-polylysine, 0.01-0.04% zinc ε-polylysine, 0.1-0.5% poloxamer, 1-2% trehalose, 0.1-0.3% cocamidopropyl betaine, 0.4-1% glycerol, 0.01-0.05% disodium magnesium EDTA, with the balance being water.

[0020] In this invention, the ε-polylysine is preferably 0.08% by mass fraction.

[0021] In this invention, the ε-polylysine zinc is preferably 0.02% by mass fraction.

[0022] In this invention, the poloxamer is preferably 0.3% by mass fraction.

[0023] In this invention, the trehalose is preferably 1.5% by mass fraction.

[0024] In this invention, the cocamidopropyl betaine is preferably 0.3% by mass fraction.

[0025] In this invention, the glycerol is preferably 0.8% by mass fraction.

[0026] In this invention, the magnesium disodium ethylenediaminetetraacetate is preferably 0.03% by mass fraction.

[0027] In this invention, the pH of the antibacterial multifunctional eye drops for contact lenses is 6.8 to 7.2, preferably 7.

[0028] In this invention, Tris base and dilute hydrochloric acid solution are preferably used as pH adjusters to adjust the pH of the antibacterial multi-functional eye drops for contact lenses.

[0029] In this invention, the poloxamer is preferably poloxamer 184.

[0030] In this invention, the water is preferably purified water.

[0031] This invention also provides a method for preparing an antibacterial multifunctional eye drop for contact lenses. Under stirring conditions, Tris base is first dissolved in water, then disodium magnesium ethylenediaminetetraacetate is added, the pH of the system is adjusted with dilute hydrochloric acid solution, and finally the remaining raw materials are dissolved in water one by one, followed by volume adjustment, filtration, and sterilization.

[0032] In this invention, Tris base is first dissolved in water to make the pH of the system weakly alkaline, and then disodium magnesium ethylenediaminetetraacetate is added and dissolved. The purpose is to chelate trace metal ions in the system and establish a stable basic environment.

[0033] In this invention, magnesium disodium ethylenediaminetetraacetate has a weaker chelating ability than EDTA. The binding of magnesium ions reduces its predatory effect on calcium ions between cells, thereby preferentially chelating catalytic heavy metal ions, greatly improving the mildness and safety of the formulation, reducing stinging sensation during use and assisting in preservation.

[0034] In this invention, the concentration of the dilute hydrochloric acid solution is preferably 0.02 mol / L.

[0035] In this invention, the stirring temperature is 40-50°C, preferably 42-48°C, and more preferably 45°C; the stirring speed is 50-200 rpm, preferably 100-150 rpm, and more preferably 130 rpm.

[0036] In this invention, the ε-polylysine zinc is preferably added in the form of a dispersion.

[0037] In this invention, the mass ratio of ε-polylysine zinc dispersion to water is 0.05-0.15:3-20, preferably 0.08-0.12:5-18, and more preferably 0.1:12.

[0038] In this invention, the ε-polylysine zinc dispersion is obtained by adding ε-polylysine zinc into water under high-speed stirring.

[0039] In this invention, the high-speed stirring speed is 800-2500 rpm, preferably 1000-2000 rpm, and more preferably 1500 rpm; the high-speed stirring time is preferably sufficient to fully disperse ε-polylysine zinc.

[0040] In this invention, as a preferred embodiment, under stirring conditions, the remaining raw materials, trehalose and glycerol, are added to the system in sequence and stirred until completely clear and dissolved. Then, ε-polylysine zinc dispersion is added, followed by ε-polylysine until completely dissolved. Finally, poloxamer 184 and cocamidopropyl betaine are added and stirred until completely transparent and dissolved. Finally, the volume is adjusted with pure water, and the mixture is homogenized, filtered, and sterilized.

[0041] 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.

[0042] Example 1

[0043] With the assistance of a high-speed shear disperser, the rotation speed was controlled at 1000 rpm, and 0.02 g of ε-polylysine zinc was slowly added to 10 g of pure water to disperse it fully, thus obtaining an ε-polylysine zinc dispersion.

[0044] Pour 80g of pure water into a preparation tank. At 40℃ and 100rpm, adjust the pH of the pure water to 8.0 using 1mM Tris base. Then, add 0.03g of disodium magnesium EDTA to the tank until dissolved. Next, add 1.5g of trehalose, 0.8g of glycerol, ε-polylysine zinc dispersion, 0.08g of ε-polylysine, 0.3g of poloxamer 184, and 0.3g of cocamidopropyl betaine sequentially. After each addition, wait for the material to dissolve and the system to clarify before adding the next material. After all materials have been added, add pure water to make up the volume to 100g. Finally, homogenize, filter, and sterilize sequentially to obtain the antibacterial multi-functional eye drops for contact lenses.

[0045] Example 2

[0046] With the assistance of a high-speed shear disperser, the rotation speed was controlled at 1500 rpm, and 0.04 g of ε-polylysine zinc was slowly added to 10 g of pure water to disperse it fully, thus obtaining an ε-polylysine zinc dispersion.

[0047] Pour 80g of pure water into a preparation tank. At 45℃ and 200rpm, adjust the pH of the pure water to 8.0 using 1mM Tris base. Then, add 0.05g of disodium magnesium EDTA to the tank until dissolved. Next, sequentially add 2g of trehalose, 0.4g of glycerol, ε-polylysine zinc dispersion, 0.1g of ε-polylysine, 0.5g of poloxamer 184, and 0.1g of cocamidopropyl betaine. After each addition, wait for the material to dissolve and the system to clarify before adding the next material. After all materials have been added, add pure water to make up the volume to 100g. Finally, homogenize, filter, and sterilize sequentially to obtain an antibacterial multi-functional eye drops for contact lenses.

[0048] Example 3

[0049] With the assistance of a high-speed shear disperser, the rotation speed was controlled at 1200 rpm, and 0.01 g of ε-polylysine zinc was slowly added to 10 g of pure water to disperse it fully, thus obtaining an ε-polylysine zinc dispersion.

[0050] Pour 80g of pure water into a preparation tank. At 45℃ and 200rpm, adjust the pH of the pure water to 8.0 using 1mM Tris base. Then, add 0.02g of disodium magnesium EDTA to the tank until dissolved. Next, add 1g of trehalose, 1g of glycerol, ε-polylysine zinc dispersion, 0.08g of ε-polylysine, 0.1g of poloxamer 184, and 0.2g of cocamidopropyl betaine sequentially. After each addition, wait for the material to dissolve and the system to clarify before adding the next material. After all materials have been added, add pure water to make up the volume to 100g. Finally, homogenize, filter, and sterilize sequentially to obtain an antibacterial multi-functional eye drops for contact lenses.

[0051] Comparative Example 1

[0052] Unlike Example 1, in this comparative example, the amount of substances such as zinc ε-polylysine was replaced with ε-polylysine.

[0053] Comparative Example 2

[0054] Unlike Example 1, no trehalose was added in this comparative example.

[0055] Comparative Example 3

[0056] Unlike Example 1, sodium magnesium ethylenediaminetetraacetate was not added in this comparative example.

[0057] The performance of the eye drops obtained in Examples 1-3 and Comparative Examples 1-3 was tested.

[0058] 1) Antibacterial test

[0059] Inoculation: Equal amounts of the eye drops obtained in Examples 1-3 and Comparative Examples 1-3 were inoculated into different containers to inoculate microorganisms or fungi, so that the initial concentration reached 10^6 CFU / mL.

[0060] Culture and counting: The inoculated samples were cultured at 23°C, and colony counts were performed at 5 min, 15 min, 30 min, 1 h, 4 h and 6 h after inoculation.

[0061] 2) Evaluation of wearing effect

[0062] One hundred volunteers, regardless of gender, were randomly selected and divided into six groups. Each group tried on the contact lenses soaked in Examples 1-3 and Comparative Examples 1-3, respectively. The lenses were soaked for 4 hours and worn for 12 hours daily for three consecutive days. Comfort was assessed using a 10-point scale, with higher scores indicating better comfort.

[0063] Table 1 shows the antibacterial rate and wearing comfort score of the eye drops obtained in Examples 1-3 and Comparative Examples 1-3 of this application at 4 hours after inoculation.

[0064] Table 1. Antibacterial rate and wearing comfort scores of the eye drops obtained in Examples 1-3 and Comparative Examples 1-3 at 4 h after inoculation.

[0065]

[0066] 3) Physical compatibility between contact lens solution and corneal contact lens

[0067] Take 30 lenses and measure and record their refractive power. Soak 5 lenses in the eye drops of Examples 1-3 and Comparative Examples 1-3 for 2 hours. Measure and record their refractive power again.

[0068] Experimental results: The refractive power of the 30 lenses after soaking was within ±0.25D of the refractive power measured before soaking, which meets the requirements.

[0069] 4) Moisturizing performance test

[0070] Prepare 36 contact lenses of the same model. Take 6 lenses from each model and soak them in standard saline solution, eye drops obtained in Examples 1-3, and Comparative Examples 1-3 for 24 hours. After soaking, remove the lenses, wipe off the surface care solution, and measure the wet weight of 54 lenses using a precision electronic balance and record the results. Place them in an environment with a temperature of 35±1℃ and a humidity of 40%±2%, and measure their weight every hour to calculate their water loss. The results are shown in Table 2.

[0071] Table 2 shows the water loss of lenses after treatment with the care solution obtained in Examples 1-3 and Comparative Examples 1-3.

[0072]

[0073] As shown in the above embodiments, this invention provides an antibacterial multifunctional eye drops for contact lenses and its preparation method. According to the above tests, the antibacterial multifunctional eye drops for contact lenses obtained by this invention have good antibacterial properties, moisturizing properties, biosafety, and high physical compatibility with contact lenses, with low irritation (average total score of Draize eye rating < 1.0). As shown in Example 1 and Comparative Example 1, ε-polylysine and zinc ε-polylysine have a synergistic bactericidal effect; when zinc ε-polylysine is replaced with an equal amount of ε-polylysine in the system, the bactericidal effect is weakened. As shown in Example 1 and Comparative Example 2, trehalose imparts a high moisturizing effect to the eye drops, and it has a synergistic and immediate moisturizing effect with glycerin. As shown in Example 1 and Comparative Example 3, sodium magnesium ethylenediaminetetraacetate, as a metal chelating agent, is used to remove catalytically oxidizing components in the eye, while also having a bactericidal effect, improving the wearing comfort of contact lenses. This invention is of great significance in solving the technical problems of high irritation, insufficient biosafety, and limited functionality in existing eye drops.

[0074] 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 multi-functional antibacterial eye drop for contact lenses, characterized in that, It consists of the following components in parts by mass: 0.05–0.15% ε-polylysine, 0.01–0.04% zinc ε-polylysine, 0.1–0.5% poloxamer, 1–2% trehalose, 0.1–0.3% cocamidopropyl betaine, 0.4–1% glycerol, 0.01–0.05% disodium magnesium EDTA, and the balance being water.

2. The antibacterial multifunctional eye drops for contact lenses according to claim 1, characterized in that, The pH of the antibacterial multi-functional eye drops for contact lenses is 6.8–7.

2.

3. The antibacterial multifunctional eye drops for contact lenses according to claim 2, characterized in that, The pH of the antibacterial multi-purpose eye drops for contact lenses was adjusted using Tris base and dilute hydrochloric acid solution as pH adjusters.

4. The antibacterial multifunctional eye drops for contact lenses according to claim 1 or 2, characterized in that, The poloxamers include poloxamer 184.

5. The method for preparing the antibacterial multifunctional eye drops for contact lenses according to any one of claims 1 to 4, characterized in that, Includes the following steps: Under stirring conditions, first dissolve the Tris base in water, then add disodium magnesium ethylenediaminetetraacetate, then adjust the pH of the system with dilute hydrochloric acid solution, and finally dissolve the remaining raw materials one by one in water, and then proceed with volume adjustment, filtration, and sterilization in sequence.

6. The method for preparing an antibacterial multifunctional eye drop for contact lenses according to claim 5, characterized in that, The stirring temperature is 40–50°C, and the stirring speed is 50–200 rpm.

7. The method for preparing an antibacterial multifunctional eye drop for contact lenses according to claim 5, characterized in that, The ε-polylysine zinc was added in the form of a dispersion. The mass ratio of ε-polylysine zinc to water in the ε-polylysine zinc dispersion is 0.05–0.15:3–20.

8. The method for preparing an antibacterial multifunctional eye drop for contact lenses according to claim 7, characterized in that, The ε-polylysine zinc dispersion is obtained by adding ε-polylysine zinc into water under high-speed stirring.

9. The method for preparing an antibacterial multifunctional eye drop for contact lenses according to claim 8, characterized in that, The high-speed stirring speed is 800-2500 rpm, and the high-speed stirring time is sufficient to fully disperse ε-polylysine zinc.

Images