An eye drop and a preparation method and application thereof

Abstract

The application provides an eye drop and a preparation method and application thereof, and the raw material of the eye drop comprises a copper ion compound, sodium hyaluronate, epigallocatechin gallate, glycyrrhizic acid, glucose oxidase, a pH regulator and sterilized ultrapure water; the raw material of the eye drop adopts multiple natural active ingredients, effectively promotes the healing of an eye wound through multiple mechanisms (including antibacterial, anti-inflammatory, antioxidant and promotion of tissue regeneration), breaks through the constraint of traditional antibiotic eye drops which may have poor effects due to drug resistance, and solves the problem of poor effect of a treatment method commonly used in clinical treatment of corneal wound infection.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of biological medicine, and in particular to an eye drop, a preparation method thereof and an application thereof. BACKGROUND

[0002] The cornea is located at the front of the eyeball and contacts the external environment, so it is more likely to be damaged, such as trauma, foreign matter, burns, chemical injury, etc. Moreover, the cornea has no blood vessels and poor nutrition, and low anti-infection ability, so it is more likely to be infected. At the same time, in recent years, the distribution of eye infection bacteria has changed significantly. For example, Pseudomonas aeruginosa was the most common pathogenic bacterium of bacterial keratitis, but in recent years, data from many domestic ophthalmic institutions showed that the pathogenic bacteria of eye infection were mainly gram-positive bacteria (about 80%), especially S. epidermidis (accounting for > 50%), and Staphylococcus aureus also occurred from time to time; among the gram-negative pathogenic bacteria, Pseudomonas aeruginosa was the most common. This disease has an acute onset, a more severe condition, and changes, and if it is not treated effectively, a series of complications may occur, such as corneal ulcer perforation, eyeball atrophy, etc. Even if the condition is controlled, there may be sequelae such as corneal scar, corneal neovascularization or corneal staphyloma, which seriously affect vision, and even lead to blindness of the patient.

[0003] Some commonly used antibiotic or hormone eye drops on the market can effectively treat the infection caused by eye corneal damage, such as levofloxacin eye drops, but long-term use can easily lead to bacterial drug resistance, making treatment more difficult, and overuse of antibiotics can also destroy the normal microbial community of the eye, leading to the occurrence of other problems. In addition, the use of hormone eye drops, such as tobramycin dexamethasone eye drops, can also cause side effects such as atrophy of eye tissue, thinning of cornea, etc., and even affect the immune system function of other parts of the body, increasing the risk of infection.

[0004] In recent years, the problem of contamination of methicillin-resistant Staphylococcus epidermidis (MRSE) has been further emphasized in clinical research, and the commonly used treatment for eye corneal wound infection in clinical practice has poor efficacy and cannot meet the needs of clinical medication. Therefore, the development of new drugs for treating eye corneal wound infection has great clinical significance in the field of eye science. SUMMARY

[0005] In order to solve the problems in the prior art, the present application provides an eye drop and a preparation method and application thereof. The raw materials of the eye drop are a plurality of natural active ingredients, which effectively promote the healing of eye wounds through a plurality of mechanisms (including antibacterial, anti-inflammatory, antioxidant and promotion of tissue regeneration), breaking through the constraints of traditional antibiotic eye drops that may have poor efficacy due to drug resistance, and solving the problem of poor efficacy of the commonly used treatment for eye corneal wound infection in clinical practice.

[0006] In order to achieve the above object, the present application provides the following technical scheme: an eye drop, raw materials including: copper ion compound, sodium hyaluronate, epigallocatechin gallate, glycyrrhizic acid, glucose oxidase, pH adjuster and sterilized ultrapure water.

[0007] Further, the raw materials include, in mass percentage: 0.03%-0.07% of copper ion compound, 0.3%-0.5% of sodium hyaluronate, 0.05%-0.1% of epigallocatechin gallate, 0.05%-0.1% of glycyrrhizic acid, 0.005%-0.01% of glucose oxidase, and the rest is pH adjuster and sterilized ultrapure water.

[0008] Further, the copper ion compound is copper sulfate or copper gluconate.

[0009] Further, the pH adjuster is sodium citrate.

[0010] The present application also provides a preparation method of the eye drop, and the specific steps are as follows:

[0011] S1, the copper ion compound, epigallocatechin gallate, glycyrrhizic acid and glucose oxidase are dissolved in sterilized ultrapure water to prepare a mixed solution A;

[0012] S2, the mixed solution A is slowly added with sodium hyaluronate under constant temperature stirring, and stirring is performed until complete dissolution;

[0013] S3, the pH adjuster is added to adjust the pH value of the solution to weak acidity, and filtration is performed to obtain the eye drop.

[0014] Further, the raw materials include, in mass percentage: 0.03%-0.07% of copper ion compound, 0.3%-0.5% of sodium hyaluronate, 0.03%-0.07% of copper ion compound, 0.3%-0.5% of sodium hyaluronate, 0.05%-0.1% of epigallocatechin gallate, 0.05%-0.1% of glycyrrhizic acid, 0.005%-0.01% of glucose oxidase, and the rest is pH adjuster and sterilized ultrapure water.

[0015] Further, in S2, the mixed solution A is slowly added with sodium hyaluronate under constant temperature stirring at 40 DEG C, and stirring is performed until complete dissolution.

[0016] Further, in S3, the pH adjuster is sodium citrate, the pH adjuster is added to adjust the pH value of the solution to 6.5, and filtration is performed to obtain the eye drop.

[0017] The present application provides an application of the eye drop in promoting corneal wound healing.

[0018] The application provides application of eye drops in resisting bacterial infection caused by Staphylococcus epidermidis, Pseudomonas aeruginosa or methicillin-resistant Staphylococcus epidermidis.

[0019] Compared with the prior art, the application has at least the following beneficial effects:

[0020] The application provides eye drops, a preparation method and application thereof, wherein copper ions are effective bactericidal components, have high bactericidal effect on Staphylococcus epidermidis, Pseudomonas aeruginosa and methicillin-resistant Staphylococcus epidermidis, and sodium hyaluronate is used as an eye solvent, which can effectively lock up moisture in eyes and keep eyes moist, and some natural active ingredients, such as epigallocatechin gallate, glycyrrhizic acid and glucose oxidase, can play a certain auxiliary therapeutic role and help to promote healing of damaged tissues in eyes, and use of a pH regulator ensures stability and comfort of the solution, and the eye drops are expected to provide a new efficient and safe solution for eye wound healing in clinical application.

[0021] Further, long-term use of antibiotic eye drops can easily lead to bacterial drug resistance, increasing the difficulty of treatment, and the use of copper ions instead of antibiotics has a very low possibility of developing drug resistance, and in eye treatment, copper ions are expected to be used as a new type of eye drop component to replace or reduce the use of antibiotics. In vitro bacteriostatic activity experiments of the eye drops show that the eye drops have broad-spectrum antibacterial properties, the antibacterial rate reaches 99%, and the risk of developing drug resistance is low, so the use of the eye drops can significantly improve the success rate of treatment and provide a safer and more effective solution for patients; meanwhile, sodium hyaluronate can also enhance the viscosity of the eye drops and prolong the residence time of the drug in the eyes, thereby improving the treatment effect.

[0022] Further, the copper ions in the eye drops containing copper ion compounds prepared by the application are successfully loaded into the sodium hyaluronate solution matrix and uniformly distributed in the solution, the eye drops have a non-homogeneous surface and a porous structure, which is beneficial to water storage and diffusion and release of copper ions, and can effectively treat epidermis and eyeball infections, significantly reduce the risk of lung MRSE infection, and timely and effectively prevent the reproduction and spread of microorganisms in the body.

[0023] Further, through animal experiments, it is found that compared with the infection group, the antibiotic eye drop group and the copper gluconate-containing eye drop group, after 14 days of treatment with the copper sulfate-containing eye drops, the corneal ulceration of the corneal damaged infected mice is reduced, edema disappears, there is no inflammatory cell, neovascularization is reduced, and the corneal defect is completely repaired. In addition, compared with the current market selling antibiotic eye drops, the eye drops of the application are inexpensive and can break through the constraints of poor effect due to drug resistance. BRIEF DESCRIPTION OF DRAWINGS

[0024] Figure 1To verify the broad-spectrum bactericidal property of the copper ion-containing compound. Figure 1 A is the bactericidal effect of copper gluconate and copper sulfate on Staphylococcus epidermidis; Figure 1 B is the bactericidal effect of copper gluconate and copper sulfate on methicillin-resistant Staphylococcus epidermidis; Figure 1 C is the bactericidal effect of copper gluconate and copper sulfate on Pseudomonas aeruginosa.

[0025] Figure 2 The results of the broad-spectrum bactericidal property of the eye drops prepared in Example 2. Figure 2 A is the bactericidal effect of the eye drops prepared in Example 2 on Staphylococcus epidermidis; Figure 2 B is the bactericidal effect of the eye drops prepared in Example 2 on methicillin-resistant Staphylococcus epidermidis; Figure 2 C is the bactericidal effect of the eye drops prepared in Example 2 on Pseudomonas aeruginosa.

[0026] Figure 3 The schematic diagram of subcutaneous injection of the eye drops prepared in Example 2 into mice and the HE staining diagram of the tissue section.

[0027] Figure 4 The treatment effect diagrams of the mice with MRSE-infected corneal wound models treated by different treatment methods for 0, 3, 7, 10, and 14 days. The red arrows in the diagrams indicate that the eyeballs of the mice have different degrees of corneal scar and ulceration.

[0028] Figure 5 The bactericidal effect of the eye drops prepared in Example 2 on the corneas of the mice after 7 days of treatment. DETAILED DESCRIPTION

[0029] The present application will be further described below in conjunction with the drawings and specific embodiments. The following examples are only used to more clearly illustrate the technical solutions of the present application, and cannot be used to limit the protection scope of the present application.

[0030] The present application provides an eye drop, the total content of which is 100% by mass percentage, and the raw materials include: 0.03% to 0.07% of a copper ion compound, 0.3% to 0.5% of sodium hyaluronate, 0.05% to 0.1% of epigallocatechin gallate, 0.05% to 0.1% of glycyrrhizic acid, 0.005% to 0.01% of glucose oxidase, and the rest is a pH adjuster and sterilized ultrapure water.

[0031] Preferably, the copper ion compound is copper sulfate or copper gluconate.

[0032] The preparation method of the above-mentioned eye drop includes the following steps:

[0033] S1, dissolve the copper ion compound, epigallocatechin gallate, glycyrrhizic acid and glucose oxidase in sterile ultrapure water to prepare a mixed solution A, keep 40-45 DEG C constant temperature stirring;

[0034] S2, under the condition of 40-45 DEG C constant temperature stirring, slowly add sodium hyaluronate, stir until completely dissolved;

[0035] S3, add pH regulator sodium citrate, adjust the pH value to 6.5, stir to make the mixture uniform, filter through 0.22-0.45 mu m filter to obtain eye drops, the copper ion in the prepared eye drops is successfully loaded into the sodium hyaluronate solution matrix, and is uniformly distributed in the solution, the eye drops have heterogeneous surface and porous structure, which is beneficial to the preservation of water and the diffusion and release of copper ions.

[0036] The corneal wound is mainly caused by eye injury, such as foreign body injury, eye contusion, acid and alkali chemical injury, etc., and bacterial infection is caused by S. epidermidis, P. aeruginosa and MRSE infection of eyeball or epidermis after corneal trauma.

[0037] The eye drops of the application introduce copper ion compound, so that the bactericidal rate of the eye drops on S. epidermidis, MRSE and P. aeruginosa reaches more than 99%, and can be used in the treatment of corneal wound healing and bacterial infection diseases caused by MRSE.

[0038] The eye drops of the application can effectively treat eye epidermis and eyeball infection, and can significantly reduce the risk of lung MRSE infection, and timely and effectively prevent the reproduction and spread of microorganisms in the body.

[0039] Example one:

[0040] The embodiment provides an eye drop, which comprises the following components in mass percentage: epigallocatechin gallate 0.1%, glycyrrhizic acid 0.1%, glucose oxidase 0.01%, copper sulfate 0.03%, sodium hyaluronate 0.5%, and the rest is pH regulator and sterilized ultrapure water.

[0041] Preparation process:

[0042] S1, dissolve 0.03% copper sulfate, 0.1% epigallocatechin gallate, 0.1% glycyrrhizic acid and 0.01% glucose oxidase in 20 mL sterile ultrapure water to prepare a mixed solution, and keep 40 DEG C constant temperature stirring;

[0043] S2, under the condition of 40 DEG C constant temperature stirring, slowly add 0.5% sodium hyaluronate, stir until completely dissolved;

[0044] S3, add pH regulator sodium citrate, adjust the pH value to 6.5, stir to mix evenly, filter through a 0.45μm filter to obtain the copper sulfate eye drops.

[0045] Example Two:

[0046] The example provides an eye drop, which comprises the following components in mass percentage: epigallocatechin gallate 0.1%, glycyrrhizic acid 0.1%, glucose oxidase 0.01%, copper sulfate 0.07%, sodium hyaluronate 0.4%, and the balance being a pH regulator and sterilized ultrapure water.

[0047] Preparation process:

[0048] S1, dissolve copper sulfate 0.07%, epigallocatechin gallate 0.1%, glycyrrhizic acid 0.1%, glucose oxidase 0.01% in 20mL sterilized ultrapure water to prepare a mixed solution, and stir at 40°C;

[0049] S2, slowly add sodium hyaluronate 0.4% under the condition of constant stirring at 40°C, and stir until completely dissolved;

[0050] S3, add pH regulator sodium citrate, adjust the pH value to 6.5, stir to mix evenly, filter through a 0.45μm filter to obtain the copper sulfate eye drops.

[0051] Example Three:

[0052] The example provides an eye drop, which comprises the following components in mass percentage: epigallocatechin gallate 0.1%, glycyrrhizic acid 0.1%, glucose oxidase 0.01%, copper gluconate 0.03%, sodium hyaluronate 0.5%, and the balance being a pH regulator and sterilized ultrapure water.

[0053] Preparation process:

[0054] S1, dissolve copper gluconate 0.03%, epigallocatechin gallate 0.1%, glycyrrhizic acid 0.1%, glucose oxidase 0.01% in 20mL sterilized ultrapure water to prepare a mixed solution, and stir at 40°C;

[0055] S2, slowly add sodium hyaluronate 0.5% under the condition of constant stirring at 40°C, and stir until completely dissolved;

[0056] S3, add pH regulator sodium citrate, adjust the pH value to 6.5, stir to mix evenly, filter through a 0.45μm filter to obtain the copper sulfate eye drops.

[0057] Example Four:

[0058] The embodiment provides an eye drop, which comprises the following components in percentage by mass: epigallocatechin gallate 0.1%, glycyrrhizic acid 0.1%, glucose oxidase 0.01%, copper gluconate 0.07%, sodium hyaluronate 0.5%, and the rest is a pH regulator and sterilized ultrapure water.

[0059] Preparation process:

[0060] S1, copper gluconate 0.07%, epigallocatechin gallate 0.1%, glycyrrhizic acid 0.1%, glucose oxidase 0.01% are dissolved in 20 mL of sterile ultrapure water to prepare a mixed solution, and constant temperature stirring is carried out at 40 DEG C;

[0061] S2, under the condition of constant temperature stirring at 40 DEG C, sodium hyaluronate 0.5% is slowly added, and stirring is carried out until complete dissolution;

[0062] S3, a pH regulator sodium citrate is added, the pH value is adjusted to 6.5, stirring is carried out to make the mixture uniform, and filtration is carried out through a 0.45 mu filter to obtain the copper gluconate eye drop.

[0063] Example five:

[0064] The embodiment provides an eye drop, which comprises the following components in percentage by mass: epigallocatechin gallate 0.1%, glycyrrhizic acid 0.1%, glucose oxidase 0.01%, copper sulfate 0.05%, sodium hyaluronate 0.3%, and the rest is a pH regulator and sterilized ultrapure water.

[0065] Preparation process:

[0066] S1, copper sulfate 0.05%, epigallocatechin gallate 0.1%, glycyrrhizic acid 0.1%, glucose oxidase 0.01% are dissolved in 20 mL of sterile ultrapure water to prepare a mixed solution, and constant temperature stirring is carried out at 40 DEG C;

[0067] S2, under the condition of constant temperature stirring at 40 DEG C, sodium hyaluronate 0.5% is slowly added, and stirring is carried out until complete dissolution;

[0068] S3, a pH regulator sodium citrate is added, the pH value is adjusted to 6.5, stirring is carried out to make the mixture uniform, and filtration is carried out through a 0.45 mu filter to obtain the copper gluconate eye drop.

[0069] Example six:

[0070] The embodiment provides an eye drop, which comprises the following components in percentage by mass: epigallocatechin gallate 0.035%, glycyrrhizic acid 0.035%, glucose oxidase 0.008%, copper gluconate 0.05%, sodium hyaluronate 0.5%, and the rest is a pH regulator and sterilized ultrapure water.

[0071] Preparation process:

[0072] S1, copper gluconate 0.05%, epigallocatechin gallate 0.035%, glycyrrhizic acid 0.035%, glucose oxidase 0.008% was dissolved in 20 mL sterile ultrapure water, prepared mixed solution, constant temperature stirring at 43℃;

[0073] S2, under the condition of constant temperature stirring at 43℃, slowly add hyaluronic acid sodium 0.5%, stirring to completely dissolved;

[0074] S3, add pH regulator sodium citrate, adjust the pH value to 6.5, stirring to make the mixture uniform, filtration, get copper sulfate eye drops.

[0075] Example seven:

[0076] The example provides an eye drop, including the following mass percent of each component: epigallocatechin gallate 0.05%, glycyrrhizic acid 0.05%, glucose oxidase 0.005%, copper sulfate 0.05%, sodium hyaluronate 0.5%, the rest is pH regulator and sterilized ultrapure water.

[0077] Preparation process:

[0078] S1, copper sulfate 0.05%, gallate 0.05%, glycyrrhizic acid 0.05%, glucose oxidase 0.005% was dissolved in 20 mL sterile ultrapure water, prepared mixed solution, constant temperature stirring at 45℃;

[0079] S2, under the condition of constant temperature stirring at 45℃, slowly add hyaluronic acid sodium 0.5%, stirring to completely dissolved;

[0080] S3, add pH regulator sodium citrate, adjust the pH value to 6.5, stirring to make the mixture uniform, filtration, get copper sulfate eye drops.

[0081] Test example 1

[0082] Copper ion broad spectrum bactericidal performance determination:

[0083] The copper sulfate solution and copper gluconate solution were prepared respectively, and the content was 0.01%, 0.03%, 0.05%, 0.07%. The drug was treated with 10 8 CFU / mL of staphylococcus epidermidis, methicillin-resistant staphylococcus epidermidis and pseudomonas aeruginosa, and the gradient plate method was used to verify the broad spectrum bactericidal performance of copper ion.

[0084] Through Figure 1 A- Figure 1 C results show that Figure 1 A is the bactericidal effect of copper gluconate and copper sulfate on staphylococcus epidermidis;Figure 1 B is the bactericidal effect of copper gluconate and copper sulfate on methicillin-resistant Staphylococcus aureus; Figure 1 C is the bactericidal effect of copper gluconate and copper sulfate on Pseudomonas aeruginosa. When the content of copper gluconate and copper sulfate is 0.07%, copper sulfate and copper gluconate have bactericidal effect on Staphylococcus aureus, methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, and copper gluconate has poorer bactericidal effect than copper sulfate. When the content of copper sulfate is 0.03%, it can inhibit the growth of almost 99.9% of Staphylococcus aureus, methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, and has broad-spectrum bactericidal property.

[0085] Test Example 2

[0086] Determination of broad-spectrum bactericidal property of eye drops:

[0087] 10 8 CFU / mL of Staphylococcus aureus, methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa were washed twice with normal saline, and the prepared eye drops of Example 2 were used for treatment for 10 8 CFU / mL of Staphylococcus aureus, methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa were washed twice with normal saline, and the prepared eye drops of Example 2 were used for treatment for 10

[0088] The eye drops used for testing were the eye drops prepared in Example 2.

[0089] As Figure 2 , Figure 2 A is the bactericidal effect of the eye drops prepared in Example 2 on Staphylococcus aureus; Figure 2 B is the bactericidal effect of the eye drops prepared in Example 2 on methicillin-resistant Staphylococcus aureus; Figure 2 C is the bactericidal effect of the eye drops prepared in Example 2 on Pseudomonas aeruginosa. The eye drops prepared in Example 2 can effectively kill Staphylococcus aureus, methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, and the bactericidal rate for the three bacteria reaches 99.9%.

[0090] In summary, the eye drops containing copper sulfate prepared in this example have high bactericidal effect on gram-positive bacteria and gram-negative bacteria, i.e. broad-spectrum bactericidal property, and are suitable for eye infections caused by bacterial infections.

[0091] Test Example 3

[0092] Biocompatibility evaluation:

[0093] The eye drops prepared in Example 2 were subcutaneously injected at 0.5 mL into the back of mice, and every 30 min, 1 Day and 3 Day, 3 mice were sacrificed, and the injection sites were photographed, and the skin tissues at the injection sites were collected for histopathological analysis by HE staining.

[0094] Results as shown in Figure 3 HE slice staining showed that the eye drops induced slight acute inflammatory reaction on the first day. On the third day, almost no inflammatory cells were observed, and the inflammation gradually weakened and disappeared as the eye drops degraded.

[0095] In summary, the copper sulfate-containing eye drops prepared in Example Two can be absorbed and degraded in vivo, and have good biocompatibility.

[0096] Test Example 4

[0097] Evaluation of the in vivo therapeutic effect of eye drops on corneal wound healing and anti-infection:

[0098] a. Construct a mouse corneal wound infection model infected with MRSE

[0099] Eight-week-old Kunming mice (male) were placed under standard conditions (12-hour light cycle / 12-hour dark cycle), free to eat and drink, and mice with existing corneal diseases were excluded. After one week of isolation, the mice were anesthetized intraperitoneally with 50 mg / mL ketamine, and three incisions were made on the corneal epithelium under a microscope using a sterile scalpel, and 0.1 mL of MRSE strain (10 8 CFU / mL) was inoculated. After 48 hours of inoculation, the mouse eyes were observed under a surgical microscope to ensure that the mouse corneal wound infection model was successfully established.

[0100] b. Treatment group settings

[0101] Corneal wound group: Mice were only constructed with a corneal wound model, and 50 μL of PBS buffer was dropped into the mouse eyes daily.

[0102] Infection group: After the rat corneal wound infection model infected with MRSE was successfully constructed, no treatment was given to the mouse eyes daily.

[0103] Antibiotic eye drop group: After the rat corneal wound infection model infected with MRSE was successfully constructed, 50 μL of levofloxacin eye drops was dropped into the mouse eyes daily.

[0104] Copper gluconate-containing eye drop group: After the rat corneal wound infection model infected with MRSE was successfully constructed, 50 μL of eye drops prepared in Example Four was dropped into the mouse eyes daily.

[0105] Copper sulfate-containing eye drop group: After the rat corneal wound infection model infected with MRSE was successfully constructed, 50 μL of eye drops prepared in Example Two was dropped into the mouse eyes daily.

[0106] c. 0-14 days after infection: Treat 3 times a day with an interval of 8 hours, and take photos on the 0th, 3rd, 7th, 10th, and 14th days to record the mouse eye wound healing.

[0107] d. On the seventh day of treatment, the eyeballs of the mice in each group were taken into 1 mL of normal saline, homogenized into a homogenate, and the survival rate of bacteria in each group was verified by gradient plate method.

[0108] Through animal experiments, it was found that the redness of the eyeballs of the mice treated with the antibiotic and the eye drops of Example Four for 14 days disappeared, the ulceration was reduced, but there was the generation of new blood vessels, and the corneal wound scar was not completely healed, such as Figure 4 , the red arrows indicate that the eyeballs of the mice have different degrees of corneal scar and ulceration; and after 14 days of treatment with the eye drops prepared in Example Two, the corneal edema of the mice disappeared, the ulcer gradually disappeared, there was no inflammation, the neovascularization was reduced, and in particular the corneal wound had already completely repaired. It shows that the eye drops prepared in Example Two have a relatively obvious effect on the recovery of the corneal wound.

[0109] Figure 5 After seven days of treatment for different groups, by homogenizing the eyeballs of the mice in each group, it was found by gradient plate method that the bactericidal rate of the eye drops prepared in Example Two (containing copper sulfate eye drops) on MRSE reached 99.9%, while the bactericidal rate of the eye drops prepared in Example Four (containing copper gluconate eye drops) on MRSE was only 90%. It shows that the eye drops prepared in Example Two (containing copper sulfate eye drops) have a better in vivo bactericidal effect.

[0110] In summary, the eye drops prepared in Example Two have a better antibacterial activity, and can effectively promote the healing of the corneal wound and the fading of the scar while having a better bactericidal effect.

Claims

1. Use of an eye drop in the manufacture of a medicament for treating a disease caused by a bacterial infection of the eye by methicillin-resistant Staphylococcus epidermidis, characterized in that, The raw materials of the eye drops include: epigallocatechin gallate 0.1%, glycyrrhizic acid 0.1%, glucose oxidase 0.01%, copper sulfate 0.07%, sodium hyaluronate 0.4%, and the rest is pH adjuster and sterilized ultrapure water; The preparation steps of the eye drops are as follows: Dissolve copper sulfate, epigallocatechin gallate, glycyrrhizic acid and glucose oxidase in sterile ultrapure water to obtain a mixed solution A; Slowly add sodium hyaluronate to the mixed solution A under constant temperature stirring at 40 DEG C until completely dissolved; Add pH adjuster to adjust the pH value of the solution to 6.5, filter to obtain the eye drops; The eye drops are used for preparing a medicine for treating eye bacterial infection diseases caused by methicillin-resistant Staphylococcus aureus.

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

3. Use according to claim 1, characterized in that, The bactericidal rate of the eye drops on methicillin-resistant Staphylococcus aureus is more than 99%.

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