Eye drops as well as preparation method and application thereof

Abstract

The invention provides eye drops and a preparation method and application thereof.The original eye drops comprise a copper ion compound, sodium hyaluronate, epigallocatechin gallate, glycyrrhizic acid, glucose oxidase, a pH regulator and sterilized ultrapure water, and the raw materials of the eye drops adopt various natural active ingredients; the healing of eye wounds is effectively promoted through various mechanisms (including antibiosis, anti-inflammation, antioxidation and tissue regeneration promotion), the constraint that the traditional antibiotic eye drops are possibly poor in treatment effect due to drug resistance is broken through, and the problem that the clinical common treatment means for cornea wound infection is poor in treatment effect is solved.

Description

[0001] This invention patent application is a divisional application of the invention patent application filed on July 12, 2024, with application number 202410937839.1 and invention title "An eye drop solution and its preparation method and application". Technical Field

[0002] This invention belongs to the field of biomedical technology, specifically to an eye drop, its preparation method, and its application. Background Technology

[0003] The cornea, located at the front of the eyeball, is in frequent contact with the external environment and is therefore more susceptible to damage from sources such as trauma, foreign bodies, burns, and chemical burns. Because the cornea lacks blood vessels, has poor nutrition, and low resistance to infection, it is more prone to infection. Furthermore, the distribution of bacteria causing eye infections has changed significantly in recent years. For example, *Pseudomonas aeruginosa* was once the most common pathogen causing bacterial keratitis, but data from several ophthalmology institutions in China in recent years show that Gram-positive bacteria are the predominant cause of eye infections (approximately 80%), especially *Staphylococcus epidermidis* (>50%), with *Staphylococcus aureus* also occurring occasionally. Among Gram-negative pathogens, *Pseudomonas aeruginosa* remains the most common. This disease has a rapid onset, is often severe, and has many changes. If left untreated, it can lead to a series of complications, such as corneal ulceration and perforation, and phthisis bulbi. Even if the condition is controlled, there may be sequelae such as corneal scarring, corneal neovascularization, or corneal staphyloma, which can seriously affect vision or even lead to blindness.

[0004] Some commonly used antibiotic or steroid eye drops can effectively treat infections caused by corneal damage, such as levofloxacin eye drops. However, long-term use can easily lead to bacterial resistance, making treatment more difficult. Furthermore, overuse of antibiotics can disrupt the normal microbiome in the eye, leading to other problems. In addition, the use of steroid eye drops, such as tobramycin-dexamethasone eye drops, may cause side effects such as eye tissue atrophy and corneal thinning, and may even affect the immune system function in other parts of the body, increasing the risk of infection.

[0005] In recent years, clinical research on the contamination problem of methicillin-resistant Staphylococcus epidermidis (MRSE) has received increasing attention. Commonly used treatments for corneal wound infections are ineffective and cannot meet clinical needs. Therefore, developing new drugs for treating corneal wound infections is of great clinical significance to the field of ophthalmology. Summary of the Invention

[0006] To address the problems existing in the prior art, this invention provides an eye drop, its preparation method, and its application. The raw materials of this eye drop use a variety of natural active ingredients, which effectively promote the healing of eye wounds through multiple mechanisms (including antibacterial, anti-inflammatory, antioxidant, and tissue regeneration promotion). This breaks through the limitation that traditional antibiotic eye drops may be ineffective due to drug resistance, and solves the problem of poor efficacy of commonly used clinical treatments for corneal wound infections.

[0007] To achieve the above objectives, the present invention provides the following technical solution: an eye drop, the raw materials of which include: copper ion compound, sodium hyaluronate, epigallocatechin gallate, glycyrrhizic acid, glucose oxidase, pH adjuster and sterile ultrapure water.

[0008] Furthermore, by mass percentage, the raw materials include: 0.03%~0.07% copper ion compounds, 0.3%-0.5% sodium hyaluronate, 0.05%~0.1% epigallocatechin gallate, 0.05%~0.1% glycyrrhizic acid, 0.005%~0.01% glucose oxidase, with the balance being pH adjuster and sterilized ultrapure water.

[0009] Furthermore, the copper ion compound is copper sulfate or copper gluconate.

[0010] Furthermore, the pH adjuster is sodium citrate.

[0011] This invention also provides a method for preparing eye drops, the specific steps of which are as follows: S1, copper ion compound, epigallocatechin gallate, glycyrrhizic acid and glucose oxidase are dissolved in sterile ultrapure water to prepare mixed solution A; S2, under constant temperature and stirring, sodium hyaluronate is slowly added to mixed solution A and stirred until completely dissolved; S3, add pH adjuster to adjust the pH of the solution to weakly acidic, filter, and obtain eye drops.

[0012] Furthermore, by mass percentage, the raw materials include: 0.03%~0.07% copper ion compound, 0.3%-0.5% sodium hyaluronate, 0.03%~0.07% copper ion compound, 0.3%-0.5% sodium hyaluronate, 0.05%~0.1% epigallocatechin gallate, 0.05%~0.1% glycyrrhizic acid, 0.005%~0.01% glucose oxidase, with the balance being pH adjuster and sterilized ultrapure water.

[0013] Furthermore, in S2, sodium hyaluronate is slowly added to mixed solution A under constant temperature stirring at 40°C, and stirred until completely dissolved.

[0014] Furthermore, in S3, the pH adjuster is sodium citrate. The pH of the solution is adjusted to 6.5 by adding the pH adjuster, and then filtered to obtain eye drops.

[0015] This invention provides an application of an eye drop in promoting the healing of corneal wounds.

[0016] This invention provides an eye drop for use in treating bacterial infections caused by Staphylococcus epidermidis, Pseudomonas aeruginosa, or methicillin-resistant Staphylococcus epidermidis.

[0017] Compared with the prior art, the present invention has at least the following beneficial effects: This invention provides an eye drop solution, its preparation method, and its application. Copper ions are the effective bactericidal component, exhibiting highly efficient bactericidal effects against Staphylococcus epidermidis, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus epidermidis. Sodium hyaluronate is used as the ophthalmic solvent, effectively locking in moisture and keeping the eyes hydrated. Simultaneously, some natural active ingredients, such as epigallocatechin gallate, glycyrrhizic acid, and glucose oxidase, can play a certain auxiliary therapeutic role, helping to promote the healing of damaged eye tissues. The use of a pH adjuster ensures the stability and comfort of the solution, and it is expected to provide a new, efficient, and safe solution for eye wound healing in clinical practice.

[0018] Furthermore, long-term use of antibiotic eye drops can easily lead to bacterial resistance, increasing the difficulty of treatment. Using copper ions instead of antibiotics greatly reduces the likelihood of bacteria developing resistance. In ocular treatment, copper ions hold promise as a novel eye drop ingredient to replace or reduce antibiotic use. In vitro antibacterial activity experiments on the eye drops of this invention revealed that they possess broad-spectrum antibacterial activity with an antibacterial rate of 99% and a low risk of developing resistance. Therefore, their use can significantly improve treatment success rates, providing patients with a safer and more effective treatment option. Simultaneously, sodium hyaluronate can enhance the viscosity of the eye drops, prolonging the drug's residence time in the eye, thereby improving the therapeutic effect.

[0019] Furthermore, the copper ions in the copper-containing compound eye drops prepared by this invention are successfully loaded into the sodium hyaluronate solution matrix and are uniformly distributed in the solution. The eye drops have a heterogeneous surface and porous structure, which is beneficial for water retention and the diffusion and release of copper ions. They can effectively treat ocular epidermal and ocular infections, significantly reduce the risk of MRSE infection in the lungs, and promptly and effectively prevent the reproduction and spread of microorganisms in the body.

[0020] Furthermore, animal experiments revealed that, compared to the infection group, the antibiotic eye drop group, and the copper gluconate-containing eye drop group, mice with corneal damage and infection treated with copper sulfate eye drops for 14 days showed reduced corneal ulceration, disappearance of edema, absence of inflammatory cells, reduced neovascularization, and complete repair of corneal defects. In addition, compared to currently available antibiotic eye drops, the eye drops of this invention are inexpensive and overcome the limitations of poor efficacy due to drug resistance. Attached Figure Description

[0021] Figure 1 To verify the broad-spectrum bactericidal properties of copper-containing compounds. Figure 1 A represents the bactericidal effects of copper gluconate and copper sulfate against Staphylococcus epidermidis; Figure 1 B represents the bactericidal effect of copper gluconate and copper sulfate against methicillin-resistant Staphylococcus epidermidis; Figure 1 C represents the bactericidal effect of copper gluconate and copper sulfate against Pseudomonas aeruginosa.

[0022] Figure 2 The results of verifying the broad-spectrum bactericidal activity of the eye drops prepared in Example 2 were verified. Figure 2 A represents the bactericidal effect of the eye drops prepared in Example 2 against Staphylococcus epidermidis; Figure 2 B represents the bactericidal effect of the eye drops prepared in Example 2 against methicillin-resistant Staphylococcus epidermidis; Figure 2 C represents the bactericidal effect of the eye drops prepared in Example 2 against Pseudomonas aeruginosa.

[0023] Figure 3 A schematic diagram of the eye drops prepared for subcutaneous injection in mice according to Example 2, and an HE staining image of tissue sections.

[0024] Figure 4 The figures show the treatment effects of different treatment methods on a mouse model of corneal wound infection caused by MRSE for 0, 3, 7, 10, and 14 days. The red arrows in the figures indicate varying degrees of corneal scarring and ulceration in the mouse eyes.

[0025] Figure 5 The bactericidal effect on the cornea of ​​mice after seven days of treatment in different groups. Detailed Implementation

[0026] The present invention will be further described below with reference to the accompanying drawings and specific embodiments. The following embodiments are only used to more clearly illustrate the technical solution of the present invention, and should not be used to limit the scope of protection of the present invention.

[0027] This invention provides an eye drop, which, by mass percentage, has a total content of 100%, and the raw materials include: 0.03%~0.07% copper ion compound, 0.3%~0.5% sodium hyaluronate, 0.05%~0.1% epigallocatechin gallate, 0.05%~0.1% glycyrrhizic acid, 0.005%~0.01% glucose oxidase, and the balance being a pH adjuster and sterile ultrapure water.

[0028] Preferably, the copper ion compound is copper sulfate or copper gluconate.

[0029] The above-mentioned method for preparing eye drops includes the following steps: S1, copper ion compound, epigallocatechin gallate, glycyrrhizic acid and glucose oxidase are dissolved in sterile ultrapure water to prepare mixed solution A, which is stirred at a constant temperature of 40℃~45℃. S2, under constant temperature and stirring at 40℃~45℃, slowly add sodium hyaluronate and stir until completely dissolved; S3, add sodium citrate as a pH adjuster to adjust the pH value to 6.5, stir to mix evenly, and filter through a 0.22μm~0.45μm filter to obtain eye drops. The copper ions in the prepared eye drops are successfully loaded into the sodium hyaluronate solution matrix and are evenly distributed in the solution. The eye drops have a heterogeneous surface and porous structure, which is conducive to water retention and the diffusion and release of copper ions.

[0030] Corneal wounds are mainly caused by external eye injuries, such as foreign body injuries, eye contusions, and chemical injuries from acids or alkalis. Bacterial infections occur after corneal trauma, leading to infection of the eyeball or epidermis by Staphylococcus epidermidis, Pseudomonas aeruginosa, or methicillin-resistant Staphylococcus epidermidis.

[0031] The eye drops of the present invention incorporate copper ion compounds, which enable the eye drops to achieve a bactericidal rate of over 99% against Staphylococcus epidermidis, methicillin-resistant Staphylococcus epidermidis, and Pseudomonas aeruginosa. They can be used to promote corneal wound healing and treat bacterial infections caused by methicillin-resistant Staphylococcus epidermidis.

[0032] The eye drops of this invention can effectively treat ocular epidermal and ocular infections, and can significantly reduce the risk of MRSE infection in the lungs, effectively and promptly preventing the reproduction and spread of microorganisms in the body.

[0033] Example 1: This embodiment provides an eye drop solution comprising the following components in the indicated mass percentages: 0.1% epigallocatechin gallate, 0.1% glycyrrhizic acid, 0.01% glucose oxidase, 0.03% copper sulfate, 0.5% sodium hyaluronate, with the remainder being a pH adjuster and sterile ultrapure water.

[0034] Preparation process: S1, Dissolve 0.03% copper sulfate, 0.1% epigallocatechin gallate, 0.1% glycyrrhizic acid, and 0.01% glucose oxidase in 20 mL of sterile ultrapure water to prepare a mixed solution, and stir at a constant temperature of 40 °C. S2, under constant temperature stirring at 40℃, slowly add 0.5% sodium hyaluronate and stir until completely dissolved; S3, add sodium citrate as a pH adjuster to adjust the pH to 6.5, stir to mix evenly, and filter through a 0.45μm filter to obtain copper sulfate eye drops.

[0035] Example 2: This embodiment provides an eye drop solution comprising the following components by mass percentage: 0.1% epigallocatechin gallate, 0.1% glycyrrhizic acid, 0.01% glucose oxidase, 0.07% copper sulfate, 0.4% sodium hyaluronate, with the balance being a pH adjuster and sterile ultrapure water.

[0036] Preparation process: S1. Dissolve 0.07% copper sulfate, 0.1% epigallocatechin gallate, 0.1% glycyrrhizic acid, and 0.01% glucose oxidase in 20 mL of sterile ultrapure water to prepare a mixed solution, and stir at a constant temperature of 40 °C. S2, under constant temperature stirring at 40℃, slowly add 0.4% sodium hyaluronate and stir until completely dissolved; S3, add sodium citrate as a pH adjuster to adjust the pH to 6.5, stir to mix evenly, and filter through a 0.45μm filter to obtain copper sulfate eye drops.

[0037] Example 3: This embodiment provides an eye drop comprising the following components in the indicated mass percentages: 0.1% epigallocatechin gallate, 0.1% glycyrrhizic acid, 0.01% glucose oxidase, 0.03% copper gluconate, 0.5% sodium hyaluronate, with the remainder being a pH adjuster and sterile ultrapure water.

[0038] Preparation process: S1, dissolve 0.03% copper gluconate, 0.1% epigallocatechin gallate, 0.1% glycyrrhizic acid, and 0.01% glucose oxidase in 20 mL of sterile ultrapure water to prepare a mixed solution, and stir at a constant temperature of 40 °C. S2, under constant temperature stirring at 40℃, slowly add 0.5% sodium hyaluronate and stir until completely dissolved; S3, add sodium citrate as a pH adjuster to adjust the pH to 6.5, stir to mix evenly, and filter through a 0.45μm filter to obtain copper gluconate eye drops.

[0039] Example 4: This embodiment provides an eye drop comprising the following components by mass percentage: 0.1% epigallocatechin gallate, 0.1% glycyrrhizic acid, 0.01% glucose oxidase, 0.07% copper gluconate, 0.5% sodium hyaluronate, with the balance being a pH adjuster and sterile ultrapure water.

[0040] Preparation process: S1, Dissolve 0.07% copper gluconate, 0.1% epigallocatechin gallate, 0.1% glycyrrhizic acid, and 0.01% glucose oxidase in 20 mL of sterile ultrapure water to prepare a mixed solution, and stir at a constant temperature of 40 °C. S2, under constant temperature stirring at 40℃, slowly add 0.5% sodium hyaluronate and stir until completely dissolved; S3, add sodium citrate as a pH adjuster to adjust the pH value to 6.5, stir to mix evenly, and filter through a 0.45μm filter to obtain copper gluconate eye drops.

[0041] Example 5: This embodiment provides an eye drop solution comprising the following components by mass percentage: 0.1% epigallocatechin gallate, 0.1% glycyrrhizic acid, 0.01% glucose oxidase, 0.05% copper sulfate, 0.3% sodium hyaluronate, with the balance being a pH adjuster and sterile ultrapure water.

[0042] Preparation process: S1. Dissolve 0.05% copper sulfate, 0.1% epigallocatechin gallate, 0.1% glycyrrhizic acid, and 0.01% glucose oxidase in 20 mL of sterile ultrapure water to prepare a mixed solution, and stir at a constant temperature of 40 °C. S2, under constant temperature stirring at 40℃, slowly add 0.5% sodium hyaluronate and stir until completely dissolved; S3, add sodium citrate as a pH adjuster to adjust the pH to 6.5, stir to mix evenly, and filter through a 0.45μm filter to obtain copper sulfate eye drops. Example 6: This embodiment provides an eye drop comprising the following components in the indicated mass percentages: 0.035% epigallocatechin gallate, 0.035% glycyrrhizic acid, 0.008% glucose oxidase, 0.05% copper gluconate, 0.5% sodium hyaluronate, with the remainder being a pH adjuster and sterile ultrapure water.

[0043] Preparation process: S1. Dissolve 0.05% copper gluconate, 0.035% epigallocatechin gallate, 0.035% glycyrrhizic acid, and 0.008% glucose oxidase in 20 mL of sterile ultrapure water to prepare a mixed solution, and stir at a constant temperature of 43 °C. S2, under constant temperature stirring at 43℃, slowly add 0.5% sodium hyaluronate and stir until completely dissolved; S3, add sodium citrate as a pH adjuster to adjust the pH value to 6.5, stir to mix evenly, filter, and obtain copper sulfate eye drops.

[0044] Example 7: This embodiment provides an eye drop comprising the following components in the indicated mass percentages: 0.05% epigallocatechin gallate, 0.05% glycyrrhizic acid, 0.005% glucose oxidase, 0.05% copper sulfate, 0.5% sodium hyaluronate, with the remainder being a pH adjuster and sterile ultrapure water.

[0045] Preparation process: S1. Dissolve 0.05% copper sulfate, 0.05% gallocatechin gallate, 0.05% glycyrrhizic acid, and 0.005% glucose oxidase in 20 mL of sterile ultrapure water to prepare a mixed solution, and stir at a constant temperature of 45 °C. S2, under constant temperature stirring at 45℃, slowly add 0.5% sodium hyaluronate and stir until completely dissolved; S3, add sodium citrate as a pH adjuster to adjust the pH value to 6.5, stir to mix evenly, filter, and obtain copper sulfate eye drops.

[0046] Test Example 1 Determination of the broad-spectrum bactericidal performance of copper ions: Copper sulfate and copper gluconate solutions were prepared with concentrations of 0.01%, 0.03%, 0.05%, and 0.07%, respectively. The drugs were then treated for 10... 8 The broad-spectrum bactericidal activity of copper ions was verified using the gradient drop plate method to detect CFU / mL of Staphylococcus epidermidis, methicillin-resistant Staphylococcus epidermidis, and Pseudomonas aeruginosa.

[0047] pass Figure 1 A~ Figure 1 The results show that, Figure 1 A represents the bactericidal effects of copper gluconate and copper sulfate against Staphylococcus epidermidis; Figure 1 B represents the bactericidal effect of copper gluconate and copper sulfate against methicillin-resistant Staphylococcus epidermidis; Figure 1 C represents the bactericidal effects of copper gluconate and copper sulfate against *Pseudomonas aeruginosa*. At a concentration of 0.07%, both copper gluconate and copper sulfate showed bactericidal effects against *Staphylococcus epidermidis*, methicillin-resistant *Staphylococcus epidermidis*, and *Pseudomonas aeruginosa*, with copper gluconate showing a weaker bactericidal effect than copper sulfate. At a concentration of 0.03%, copper sulfate inhibited the growth of almost 99.9% of *Staphylococcus epidermidis*, methicillin-resistant *Staphylococcus epidermidis*, and *Pseudomonas aeruginosa*, demonstrating broad-spectrum bactericidal activity.

[0048] Test Example 2 Determination of the broad-spectrum bactericidal properties of eye drops: 10 respectively 8 Staphylococcus epidermidis, methicillin-resistant Staphylococcus epidermidis, and Pseudomonas aeruginosa (CFU / mL) were washed twice with physiological saline and treated with the drug for 10 minutes. 8 The broad-spectrum bactericidal properties of the eye drops prepared in Example 2 were verified using the gradient drop plate method with CFU / mL of Staphylococcus epidermidis, methicillin-resistant Staphylococcus epidermidis, and Pseudomonas aeruginosa.

[0049] The eye drops used in the test were the eye drops prepared in Example 2.

[0050] like Figure 2 , Figure 2 A represents the bactericidal effect of the eye drops prepared in Example 2 against Staphylococcus epidermidis; Figure 2 B represents the bactericidal effect of the eye drops prepared in Example 2 against methicillin-resistant Staphylococcus epidermidis; Figure 2 C represents the bactericidal effect of the eye drops prepared in Example 2 against Pseudomonas aeruginosa. The eye drops prepared in Example 2 can effectively kill Staphylococcus epidermidis, methicillin-resistant Staphylococcus epidermidis, and Pseudomonas aeruginosa, with a bactericidal rate of 99.9% against all three bacteria.

[0051] In summary, the copper sulfate eye drops prepared in Example 2 have a high bactericidal effect against both Gram-positive and Gram-negative bacteria, i.e., broad-spectrum bactericidal activity, and are suitable for eye infections caused by bacterial infections.

[0052] Test Example 3 Biocompatibility assessment: 0.5 mL of the eye drops prepared in Example 2 was subcutaneously injected into the back of mice. Three mice were sacrificed every 30 minutes, 1 day, and 3 days. The injection sites were photographed, and the skin tissue at the injection sites was collected for histopathological analysis by HE staining.

[0053] The results are as follows Figure 3As shown, HE staining of the sections indicated that the eye drops induced a mild acute inflammatory response on the first day. Almost no inflammatory cells were observed on the third day, and the inflammation gradually subsided and disappeared as the eye drops degraded.

[0054] In summary, the copper sulfate-containing eye drops prepared in Example 2 can be absorbed and degraded in vivo, exhibiting good biocompatibility.

[0055] Test Example 4 Evaluation of the in vivo therapeutic effect of eye drops on promoting corneal wound healing and fighting infection: a. Constructing a mouse model of corneal wound infection caused by MRSE. Eight-week-old male Kunming mice were placed under standard conditions (12-hour light / 12-hour dark cycle) with free access to food and water, excluding mice with pre-existing corneal diseases. After one week of isolation, the mice were anesthetized by intraperitoneal injection of 50 mg / mL ketamine. Under a microscope, three incisions were made in the center of the corneal epithelium using a sterile scalpel, and 0.1 mL of MRSE strain (10) was inoculated. 8 (CFU / mL). Forty-eight hours after inoculation, the mice's eyes were observed using a surgical microscope to ensure the successful establishment of the mouse corneal wound infection model.

[0056] b. Processing Group Settings Corneal wound group: Mice were used to establish a corneal wound model and 50 μL of PBS buffer was dropped into their eyes daily.

[0057] Infection group: After the successful establishment of the MRSE-infected corneal wound model in rats, no medication was applied daily.

[0058] Antibiotic eye drops group: After successfully establishing the MRSE-infected corneal wound model in rats, 50 μL of levofloxacin eye drops were administered to the eyes of mice daily.

[0059] Copper gluconate eye drops group: After successfully establishing the MRSE-infected corneal wound model in rats, 50 μL of the eye drops prepared in Example 4 were instilled into the eyes of the mice daily.

[0060] Copper sulfate-containing eye drops group: After successfully establishing the MRSE-infected corneal wound model in rats, 50 μL of the eye drops prepared in Example 2 were administered to the eyes of the mice daily.

[0061] c. Days 0-14 post-infection: Treat 3 times daily, 8 hours apart, and take photos on days 0, 3, 7, 10, and 14 to record the healing of the mouse eyeball wound.

[0062] d. On the seventh day of treatment, mouse eyeballs from each group were taken into 1 mL of physiological saline, homogenized into a homogenate, and the bacterial survival rate of each group was verified by gradient drop plate method.

[0063] Animal experiments revealed that after 14 days of treatment with antibiotics and the eye drops from Example 4, eye redness and swelling in mice disappeared, and ulceration was reduced. However, neovascularization was observed, and corneal wound scars did not heal completely. Figure 4 The red arrows indicate that the mice all exhibited varying degrees of corneal scarring and ulceration. After 14 days of treatment with the eye drops prepared in Example 2, the mice's corneal edema disappeared, the ulceration gradually subsided, inflammation was absent, neovascularization decreased, and the corneal wounds were completely healed. This demonstrates that the eye drops prepared in Example 2 have a significant effect on corneal wound recovery.

[0064] Figure 5 After seven days of treatment in different groups, the eyeballs of mice in each group were homogenized and subjected to a gradient droplet method. The results showed that the eye drops prepared in Example 2 (containing copper sulfate) achieved a 99.9% bactericidal rate against MRSE, while the eye drops prepared in Example 4 (containing copper gluconate) only achieved a 90% bactericidal rate against MRSE. This indicates that the eye drops prepared in Example 2 (containing copper sulfate) have a better in vivo bactericidal effect.

[0065] In summary, the eye drops prepared in Example 2 have good antibacterial activity. While having a good bactericidal effect, they can also effectively promote the healing of corneal wounds and the fading of scars.

Claims

1. The application of an eye drop in the preparation of a drug for promoting corneal wound healing, characterized in that, The raw materials of the eye drops include: 0.1% epigallocatechin gallate, 0.1% glycyrrhizic acid, 0.01% glucose oxidase, 0.07% copper sulfate, 0.4% sodium hyaluronate, with the remainder being pH adjuster and sterile ultrapure water; or The raw materials of the eye drops include: 0.1% epigallocatechin gallate, 0.1% glycyrrhizic acid, 0.01% glucose oxidase, 0.07% copper gluconate, 0.5% sodium hyaluronate, with the remainder being pH adjuster and sterile ultrapure water; The specific steps for preparing the eye drops are as follows: Copper sulfate / copper gluconate, epigallocatechin gallate, glycyrrhizic acid, and glucose oxidase were dissolved in sterile ultrapure water to prepare mixed solution A. Sodium hyaluronate was slowly added to mixed solution A under constant temperature and stirring at 40°C, and stirred until completely dissolved; Add a pH adjuster to adjust the pH of the solution to 6.5, filter, and obtain eye drops; The eye drops are used to prepare a medicine that promotes the healing of corneal wounds.

2. The application according to claim 1, characterized in that, The pH adjuster is sodium citrate.

3. The application according to claim 1, characterized in that, The corneal trauma mentioned refers to bacterial infection caused by eye injury, including Staphylococcus epidermidis, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus epidermidis infection.

4. The application according to claim 3, characterized in that, The eye drops have a bactericidal rate of over 99% against Staphylococcus epidermidis, methicillin-resistant Staphylococcus epidermidis, and Pseudomonas aeruginosa.

5. The use of an eye drop in the preparation of a medicine for treating ocular epidermal and ocular infections, characterized in that, The raw materials of the eye drops include: 0.1% epigallocatechin gallate, 0.1% glycyrrhizic acid, 0.01% glucose oxidase, 0.07% copper sulfate, 0.4% sodium hyaluronate, with the remainder being pH adjuster and sterile ultrapure water; or The raw materials of the eye drops include: 0.1% epigallocatechin gallate, 0.1% glycyrrhizic acid, 0.01% glucose oxidase, 0.07% copper gluconate, 0.5% sodium hyaluronate, with the remainder being pH adjuster and sterile ultrapure water; The specific steps for preparing the eye drops are as follows: Copper sulfate / copper gluconate, epigallocatechin gallate, glycyrrhizic acid, and glucose oxidase were dissolved in sterile ultrapure water to prepare mixed solution A. Sodium hyaluronate was slowly added to mixed solution A under constant temperature and stirring at 40°C, and stirred until completely dissolved; Add a pH adjuster to adjust the pH of the solution to 6.5, filter, and obtain eye drops; The eye drops are used to prepare medicines for treating ocular epidermal and ocular infections.

6. The application according to claim 5, characterized in that, The pH adjuster is sodium citrate.

7. The application according to claim 5, characterized in that, The eye drops are effective against Staphylococcus epidermidis, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus epidermidis infections. The eye drops have a bactericidal rate of over 99% against Staphylococcus epidermidis, methicillin-resistant Staphylococcus epidermidis, and Pseudomonas aeruginosa.

8. The use of an eye drop in the preparation of a drug to reduce the risk of pulmonary MRSE infection, characterized in that, The raw materials of the eye drops include: 0.1% epigallocatechin gallate, 0.1% glycyrrhizic acid, 0.01% glucose oxidase, 0.07% copper sulfate, 0.4% sodium hyaluronate, with the remainder being pH adjuster and sterile ultrapure water; or The raw materials of the eye drops include: 0.1% epigallocatechin gallate, 0.1% glycyrrhizic acid, 0.01% glucose oxidase, 0.07% copper gluconate, 0.5% sodium hyaluronate, with the remainder being pH adjuster and sterile ultrapure water; The specific steps for preparing the eye drops are as follows: Copper sulfate / copper gluconate, epigallocatechin gallate, glycyrrhizic acid, and glucose oxidase were dissolved in sterile ultrapure water to prepare mixed solution A. Sodium hyaluronate was slowly added to mixed solution A under constant temperature and stirring at 40°C, and stirred until completely dissolved; Add a pH adjuster to adjust the pH of the solution to 6.5, filter, and obtain eye drops; The eye drops are used to prepare a drug that reduces the risk of MRSE infection in the lungs.

9. The application according to claim 8, characterized in that, The pH adjuster is sodium citrate.

10. The application according to claim 8, characterized in that, The eye drops have a bactericidal rate of over 99% against methicillin-resistant Staphylococcus epidermidis.

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