A kind of wetting boric acid eye drops and preparation method thereof

Abstract

The present invention relates to the technical field of eye drops, and specifically discloses a kind of wetting boric acid eye drops. The present invention also discloses a preparation method of the above-mentioned wetting boric acid eye drops, boric acid, chlorhexidine gluconate solution, and calcium disodium edetate are added to water, and stirred at 60-70°C to obtain a boric acid complex; sodium hyaluronate and sodium alginate are added to water and stirred, and hypromellose is added, and stirred at 30-40°C to obtain a hypromellose complex; soy lecithin, cholesterol, and ethylparaben are added to chloroform and stirred to obtain phase A; collagen and carboxymethyl chitosan are added to citric acid aqueous solution and stirred to obtain phase B; phase A is added to phase B under stirring, ultrasonic treatment, 50-60°C vacuum rotary evaporation to remove chloroform, citric acid aqueous solution is added for hydration, ultrasonic treatment, and filtration to obtain liposomes; boric acid complex, hypromellose complex, and liposomes are mixed evenly, and the pH value of the adjustment system is 6.5-7.5.

Description

Technical Field

[0001] The invention relates to the technical field of eye drops, in particular to a wetting boric acid eye drop and a preparation method thereof. Background Art

[0002] As people's lifestyles change, they spend more and more time using their eyes. With the development of electronic products in modern society, people are prone to eye fatigue and dry eyes when they watch electronic screens for a long time for work or entertainment. Eye drops that can relieve eye fatigue and dry eyes are gradually gaining attention.

[0003] Currently, most eye drops on the market have a short duration of action and can only relax the eyes briefly. They have poor durability. If eye drops are used frequently, people will easily become overly dependent on them, which will not only affect the balance of eye flora, but may also aggravate the impact on eye health. At the same time, the efficacy will become less and less obvious.

[0004] Therefore, how to prepare an eye drop that can not only keep the eyes moist but also has a long-lasting and durable effect has become a technical problem that needs to be solved at present. Summary of the invention

[0005] The purpose of the present invention is to solve the shortcomings of the prior art and to propose a moistening boric acid eye drop and a preparation method thereof.

[0006] A moistening boric acid eye drop, the raw materials of which include, by mass, 10-30 parts of boric acid, 0.002-0.004 parts of chlorhexidine gluconate, 0.1-1 parts of disodium edetate, 0.01-0.05 parts of sodium hyaluronate, 0.1-1 parts of sodium alginate, 1-5 parts of hydroxypropyl methylcellulose, 10-20 parts of soybean lecithin, 10-20 parts of cholesterol, 0.1-1 parts of ethyl paraben, 10-20 parts of collagen and 0.1-1 parts of carboxymethyl chitosan.

[0007] Preferably, the molecular weight of collagen is 2-5 kDa.

[0008] The preparation method of the above-mentioned moistening boric acid eye drops comprises the following steps:

[0009] S1. Add boric acid, chlorhexidine gluconate solution and calcium disodium ethylenediaminetetraacetate into water and stir evenly at 60-70° C. to obtain a boric acid complex;

[0010] S2, adding sodium hyaluronate and sodium alginate into water and stirring for 1-5 hours, adding hydroxypropyl methylcellulose, stirring at 30-40° C. for 10-30 minutes, to obtain a hydroxypropyl methylcellulose complex;

[0011] S3, adding soybean lecithin, cholesterol and ethyl paraben to chloroform and stirring evenly to obtain phase A;

[0012] Add collagen and carboxymethyl chitosan to the citric acid aqueous solution and stir evenly to obtain phase B;

[0013] Add phase A to phase B under stirring, treat with ultrasound for 1-2h, remove chloroform by vacuum rotary evaporation at 50-60°C, add citric acid aqueous solution for hydration, treat with ultrasound for 1-5min, and filter to obtain liposomes;

[0014] S4. Evenly mix the boric acid complex, hydroxypropyl methylcellulose complex and liposome, and adjust the pH value of the system to 6.5-7.5.

[0015] Preferably, in S1, the mass fraction of the chlorhexidine gluconate solution is 20±2%.

[0016] Preferably, in S3, the pH value of the citric acid aqueous solution is 4.6-4.8.

[0017] Preferably, in S3, the ultrasonic frequency is 20-25 kHz.

[0018] Preferably, in S3, 220 nm filter membrane is used for filtration.

[0019] Preferably, in S3, a sodium hydroxide solution with a concentration of 0.1-0.5 mol / L is used to adjust the pH value of the system to 6.5-7.5.

[0020] Beneficial effects:

[0021] The present invention utilizes soybean lecithin and cholesterol to form a gel structure, adopts nanoliposomes formed by collagen coating, and is compounded with sodium hyaluronate and hydroxypropyl methylcellulose, which can not only increase the affinity to the eye, but also utilize the hydrophilic groups on the surface to react with sodium alginate to form a composite network structure with strong water retention and water holding properties. During use, as the network structure decomposes and destroys, the lipophilic end of the lecithin is further adsorbed on the lipid layer on the surface of the tear film, and adjacent structures form a connected coating layer, so that the eye drops have a better repairing effect, thereby achieving the effect of keeping the eyes moist for a long time and relieving the symptoms of dry eyes for a long time.

[0022] The liposome obtained by the present invention has a large gap inside, which not only has better water retention capacity, is conducive to keeping the eyes moist, but also can significantly enhance the air permeability of the system, and has good oxygen permeability while ensuring that the eyes are kept moist for a long time. Collagen and carboxymethyl chitosan are compounded into the liposome shell layer, and the carboxymethyl chitosan has a high load strength. It is then compounded with calcium disodium ethylenediaminetetraacetate and hydroxypropyl methylcellulose in the boric acid complex to form a network structure, so that the carboxymethyl chitosan load stability is extremely high, and the antibacterial effect is good when combined with the internal ethyl paraben, which not only has little stimulation but also has a long antibacterial effect, and effectively ensures eye health.

[0023] When the eye drops are added to the eyes, their network structure forms a connection on the surface of the tear film lipid layer, which not only reduces the loss of water on the surface of the tear film lipid layer, but also has the effect of keeping the eyes moist for a long time and relieving dry eye symptoms for a long time. At the same time, the preparation method is simple and suitable for large-scale promotion and application. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 The pH value change curves of the eye drops obtained in Example 5 during storage under high temperature (60°C), low temperature (4°C) and strong light (4500Lx) conditions for 10 days.

[0025] Figure 2 The figure is a comparison chart of the antibacterial effects of the eye drops obtained in Example 5, Comparative Example 1 and the eye drops used in Comparative Example 2.

[0026] Figure 3 It is a comparison chart of tear secretion amount of Example 5 group, Comparative Example 1 group and Comparative Example 2 group at different time points.

[0027] Figure 4 The mildness scores of Example 5, Comparative Example 1 and Comparative Example 2 were given. DETAILED DESCRIPTION

[0028] The present invention will be further explained below in conjunction with specific embodiments.

[0029] The collagen used below was purchased from Shandong Guomu Peptide Valley Health Technology Co., Ltd.

[0030] Example 1

[0031] A moistening boric acid eye drop, the raw materials of which include: 10g of boric acid, 0.002g of chlorhexidine gluconate, 0.1g of disodium edetate, 0.01g of sodium hyaluronate, 0.1g of sodium alginate, 1g of hydroxypropyl methylcellulose, 10g of soybean lecithin, 10g of cholesterol, 0.1g of ethylparaben, 10g of collagen with a molecular weight of 2kDa, and 0.1g of carboxymethyl chitosan.

[0032] The preparation method of the above-mentioned moistening boric acid eye drops comprises the following steps:

[0033] S1. Add boric acid, 18% chlorhexidine gluconate solution and calcium disodium ethylenediaminetetraacetate into 300 g of water and stir evenly at 60° C. to obtain a boric acid complex.

[0034] S2, adding sodium hyaluronate and sodium alginate into 300 g of water and stirring for 1 h, adding hypromellose, stirring at 30° C. for 10 min to obtain a hypromellose complex;

[0035] S3, adding soybean lecithin, cholesterol and ethylparaben to 50 g of chloroform and stirring evenly to obtain phase A;

[0036] Add collagen and carboxymethyl chitosan to 400 g of pH = 4.6-4.8 citric acid aqueous solution and stir evenly to form phase B;

[0037] Add phase A to phase B under stirring, perform ultrasonic treatment for 1 h at an ultrasonic frequency of 20 kHz, remove chloroform by vacuum rotary evaporation at 50°C, add 50 g of pH = 4.6-4.8 citric acid aqueous solution for hydration, perform ultrasonic treatment for 1 min, and filter using a 220 nm filter membrane to obtain liposomes;

[0038] S4. Evenly mix the boric acid complex, the hydroxypropyl methylcellulose complex and the liposome, and adjust the pH value of the system to 6.5-7.5 using a 0.1 mol / L sodium hydroxide solution.

[0039] Example 2

[0040] A moistening boric acid eye drop, whose raw materials include: 30g of boric acid, 0.004g of chlorhexidine gluconate, 1g of disodium edetate, 0.05g of sodium hyaluronate, 1g of sodium alginate, 5g of hydroxypropyl methylcellulose, 20g of soybean lecithin, 20g of cholesterol, 1g of ethylparaben, 20g of collagen with a molecular weight of 5kDa, and 1g of carboxymethyl chitosan.

[0041] The preparation method of the above-mentioned moistening boric acid eye drops comprises the following steps:

[0042] S1. Add boric acid, 22% chlorhexidine gluconate solution and calcium disodium ethylenediaminetetraacetate into 500 g of water and stir evenly at 70° C. to obtain a boric acid complex.

[0043] S2, adding sodium hyaluronate and sodium alginate into 500 g of water and stirring for 5 h, adding hydroxypropyl methylcellulose and stirring at 40° C. for 30 min to obtain a hydroxypropyl methylcellulose complex;

[0044] S3, adding soybean lecithin, cholesterol and ethylparaben to 150 g of chloroform and stirring evenly to obtain phase A;

[0045] Add collagen and carboxymethyl chitosan to 800 g of pH = 4.6-4.8 citric acid aqueous solution and stir evenly to obtain phase B;

[0046] Add phase A to phase B under stirring, perform ultrasonic treatment for 2 h at an ultrasonic frequency of 25 kHz, remove chloroform by vacuum rotary evaporation at 60°C, add 150 g of pH = 4.6-4.8 citric acid aqueous solution for hydration, perform ultrasonic treatment for 5 min, and filter using a 220 nm filter membrane to obtain liposomes;

[0047] S4. Evenly mix the boric acid complex, the hydroxypropyl methylcellulose complex and the liposome, and adjust the pH value of the system to 6.5-7.5 using a 0.5 mol / L sodium hydroxide solution.

[0048] Example 3

[0049] A moistening boric acid eye drop, whose raw materials include: 15g of boric acid, 0.0035g of chlorhexidine gluconate, 0.3g of disodium edetate, 0.04g of sodium hyaluronate, 0.3g of sodium alginate, 4g of hydroxypropyl methylcellulose, 12g of soybean lecithin, 17g of cholesterol, 0.3g of ethylparaben, 18g of collagen with a molecular weight of 3kDa, and 0.3g of carboxymethyl chitosan.

[0050] The preparation method of the above-mentioned moistening boric acid eye drops comprises the following steps:

[0051] S1. Add boric acid, 20% chlorhexidine gluconate solution and calcium disodium edetate into 450 g of water and stir evenly at 62° C. to obtain a boric acid complex.

[0052] S2, adding sodium hyaluronate and sodium alginate into 450 g of water and stirring for 2 h, adding hydroxypropyl methylcellulose, stirring at 37° C. for 15 min, to obtain a hydroxypropyl methylcellulose complex;

[0053] S3, adding soybean lecithin, cholesterol and ethylparaben to 120 g of chloroform and stirring evenly to obtain phase A;

[0054] Add collagen and carboxymethyl chitosan to 500 g of pH = 4.6-4.8 citric acid aqueous solution and stir evenly to obtain phase B;

[0055] Add phase A to phase B under stirring, perform ultrasonic treatment for 100 min at an ultrasonic frequency of 21 kHz, remove chloroform by vacuum rotary evaporation at 58°C, add 80 g of pH = 4.6-4.8 citric acid aqueous solution for hydration, perform ultrasonic treatment for 4 min, and filter using a 220 nm filter membrane to obtain liposomes;

[0056] S4. Evenly mix the boric acid complex, the hydroxypropyl methylcellulose complex and the liposome, and adjust the pH value of the system to 6.5-7.5 using a 0.2 mol / L sodium hydroxide solution.

[0057] Example 4

[0058] A moistening boric acid eye drop, the raw materials of which include: 25g of boric acid, 0.0025g of chlorhexidine gluconate, 0.7g of disodium edetate, 0.02g of sodium hyaluronate, 0.7g of sodium alginate, 2g of hydroxypropyl methylcellulose, 18g of soybean lecithin, 13g of cholesterol, 0.7g of ethylparaben, 12g of collagen with a molecular weight of 4kDa, and 0.7g of carboxymethyl chitosan.

[0059] The preparation method of the above-mentioned moistening boric acid eye drops comprises the following steps:

[0060] S1. Add boric acid, 20% chlorhexidine gluconate solution and calcium disodium edetate into 350 g of water and stir evenly at 68° C. to obtain a boric acid complex.

[0061] S2, adding sodium hyaluronate and sodium alginate into 350 g of water and stirring for 4 h, adding hydroxypropyl methylcellulose, stirring at 33° C. for 25 min, to obtain a hydroxypropyl methylcellulose complex;

[0062] S3, adding soybean lecithin, cholesterol and ethylparaben to 80 g of chloroform and stirring evenly to obtain phase A;

[0063] Add collagen and carboxymethyl chitosan to 700 g of pH = 4.6-4.8 citric acid aqueous solution and stir evenly to form phase B;

[0064] Add phase A to phase B under stirring, perform ultrasonic treatment for 80 min at an ultrasonic frequency of 24 kHz, remove chloroform by vacuum rotary evaporation at 52°C, add 120 g of pH = 4.6-4.8 citric acid aqueous solution for hydration, perform ultrasonic treatment for 2 min, and filter using a 220 nm filter membrane to obtain liposomes;

[0065] S4. Evenly mix the boric acid complex, the hydroxypropyl methylcellulose complex and the liposome, and adjust the pH value of the system to 6.5-7.5 using a 0.4 mol / L sodium hydroxide solution.

[0066] Example 5

[0067] A moistening boric acid eye drop, whose raw materials include: 20g of boric acid, 0.003g of chlorhexidine gluconate, 0.5g of disodium edetate, 0.03g of sodium hyaluronate, 0.5g of sodium alginate, 3g of hydroxypropyl methylcellulose, 15g of soybean lecithin, 15g of cholesterol, 0.5 parts of ethyl paraben, 15g of collagen with a molecular weight of 3kDa, and 0.5g of carboxymethyl chitosan.

[0068] The preparation method of the above-mentioned moistening boric acid eye drops comprises the following steps:

[0069] S1. Add boric acid, 20% chlorhexidine gluconate solution and calcium disodium ethylenediaminetetraacetate into 400 g of water and stir evenly at 65° C. to obtain a boric acid complex.

[0070] S2, adding sodium hyaluronate and sodium alginate into 400 g of water and stirring for 3 h, adding hydroxypropyl methylcellulose and stirring at 35° C. for 20 min to obtain a hydroxypropyl methylcellulose complex;

[0071] S3, adding soybean lecithin, cholesterol and ethylparaben to 100 g of chloroform and stirring evenly to obtain phase A;

[0072] Add collagen and carboxymethyl chitosan to 600 g of pH = 4.6-4.8 citric acid aqueous solution and stir evenly to form phase B;

[0073] Add phase A to phase B under stirring, perform ultrasonic treatment for 90 min at an ultrasonic frequency of 22.5 kHz, remove chloroform by vacuum rotary evaporation at 55°C, add 100 g of pH = 4.6-4.8 citric acid aqueous solution for hydration, perform ultrasonic treatment for 3 min, and filter using a 220 nm filter membrane to obtain liposomes;

[0074] S4. Evenly mix the boric acid complex, the hydroxypropyl methylcellulose complex and the liposome, and adjust the pH value of the system to 6.5-7.5 using a 0.3 mol / L sodium hydroxide solution.

[0075] The eye drops obtained in this example were stored under high temperature (60°C), low temperature (4°C) and strong light (4500Lx) conditions for 10 days, and samples were taken on days 0, 5 and 10, respectively, and no foreign matter visible to the naked eye was found; the pH value was tested, as shown in FIG. Figure 1 As shown, the pH value of the eye drops obtained in this example does not change significantly, which proves that the eye drops obtained in the present invention have good stability.

[0076] Comparative Example 1

[0077] A moistening boric acid eye drop, whose raw materials include: 20g of boric acid, 0.003g of chlorhexidine gluconate, 0.5g of disodium edetate, 0.03g of sodium hyaluronate, 0.5g of sodium alginate, 3g of hydroxypropyl methylcellulose, 15g of soybean lecithin, 15g of cholesterol, 0.5g of ethylparaben, 15g of collagen with a molecular weight of 3kDa, and 0.5g of carboxymethyl chitosan.

[0078] The preparation method of the above-mentioned moistening boric acid eye drops comprises the following steps:

[0079] S1. Add boric acid, 20% chlorhexidine gluconate solution and calcium disodium ethylenediaminetetraacetate into 400 g of water and stir evenly at 65° C. to obtain a boric acid complex.

[0080] S2, adding sodium hyaluronate and sodium alginate into 400 g of water and stirring for 3 h, adding hydroxypropyl methylcellulose and stirring at 35° C. for 20 min to obtain a hydroxypropyl methylcellulose complex;

[0081] S3, adding soybean lecithin, cholesterol, ethyl paraben, collagen, and carboxymethyl chitosan to 700 g of pH = 4.6-4.8 citric acid aqueous solution and stirring evenly to obtain a premix;

[0082] S4. Evenly mix the boric acid complex, the hydroxypropyl methylcellulose complex and the premix, and adjust the pH value of the system to 6.5-7.5 using a 0.3 mol / L sodium hydroxide solution.

[0083] Comparative Example 2

[0084] Ordinary boric acid eye drops (purchased from Jiangxi Shiming Pharmaceutical Co., Ltd.).

[0085] Referring to the requirements of the antibacterial efficacy test method in 1121 of the fourth general rule of the Chinese Pharmacopoeia 2020 edition, the eye drops obtained in Example 5, Comparative Example 1 and the eye drops used in Comparative Example 2 were tested for antibacterial effect, and the antibacterial data of the finished products on Escherichia coli and Staphylococcus aureus were recorded, and the lg value reduced in 24 hours was recorded. Figure 2 As shown, each group had an antibacterial effect.

[0086] 33 patients diagnosed with dry eye disease in the outpatient clinic were selected and randomly divided into 3 groups, each with 11 patients (there were no significant differences in gender and age among the groups). The eye drops obtained in Example 5 were dripped in the Example 5 group, the eye drops obtained in Comparative Example 1 were dripped in the Comparative Example 1 group, and the eye drops used in Comparative Example 2 were dripped in the Comparative Example 2 group.

[0087] Referring to the tear secretion test steps, the tear secretion volume was tested before use, and then tested again 10min, 30min, and 60min after use.

[0088] Then, each group of experimenters continued to conduct comparative experiments, instilling the corresponding eye drops 3 times a day, 1 drop / time. The corresponding instillation time of each experimental group was the same, and it was used continuously for 8 weeks. The tear secretion volume before the eye drops were instilled after 8 weeks of use was recorded.

[0089] like Figure 3 As shown, the eye drops obtained in Example 5 effectively promote tear secretion and relieve dry eyes, and at the same time can further prolong the time of keeping the eyes moist, and can relieve dry eye symptoms for a long time, which is better than Comparative Examples 1-2 (P < 0.05).

[0090] After the first instillation of the corresponding eye drops, the experimenters in each group scored the mildness. The scoring criteria were as follows: mild and non-irritating 10 points → not mild and severely irritating 0 points.

[0091] like Figure 4 As shown, the eye drops obtained in Example 5 are the mildest and do not irritate the eyes.

[0092] The applicant believes that the above results are caused by the fact that the present invention utilizes soybean lecithin and cholesterol to form a gel structure, and adopts nanoliposomes formed by collagen coating, which are compounded with sodium hyaluronate and hydroxypropyl methylcellulose, which can not only increase the affinity to the eye, but also utilize the hydrophilic groups on the surface to react with sodium alginate to form a composite network structure, which has strong water retention and water holding capacity, and during use, as the network structure decomposes and destroys, the lipophilic end of the lecithin is further adsorbed on the lipid layer on the surface of the tear film, and the adjacent structures form a connected coating layer, so that the eye drops have a better repair effect, and achieve the effect of keeping the eyes moist for a long time and relieving the symptoms of dry eyes for a long time. The liposomes obtained by the present invention have a large gap inside, which not only has a better water retention capacity, is conducive to keeping the eyes moist, but also can significantly enhance the air permeability of the system, and has good oxygen permeability while ensuring that the eyes are kept moist for a long time. Collagen and carboxymethyl chitosan are compounded into the liposome shell. Carboxymethyl chitosan has high loading strength, and forms a network structure with calcium disodium ethylenediaminetetraacetate and hydroxypropyl methylcellulose in the boric acid complex, making the loading stability of carboxymethyl chitosan extremely high. It has a good antibacterial effect when combined with the internal ethyl paraben, effectively ensuring eye health. When the eye drops are added to the eyes, their network structure forms a connection on the surface of the tear film lipid layer, which not only reduces the loss of water on the surface of the tear film lipid layer, but also has the effect of keeping the eyes moist for a long time and relieving dry eye symptoms for a long time.

[0093] The above description is only a preferred specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Any technician familiar with the technical field can make equivalent replacements or changes according to the technical scheme and inventive concept of the present invention within the technical scope disclosed by the present invention, which should be covered by the protection scope of the present invention.

Claims

1. A moistening boric acid eye drop, characterized in that: The raw materials include, by mass: 10-30 parts of boric acid, 0.002-0.004 parts of chlorhexidine gluconate, 0.1-1 parts of disodium edetate, 0.01-0.05 parts of sodium hyaluronate, 0.1-1 parts of sodium alginate, 1-5 parts of hydroxypropyl methylcellulose, 10-20 parts of soybean lecithin, 10-20 parts of cholesterol, 0.1-1 parts of ethyl paraben, 10-20 parts of collagen, and 0.1-1 parts of carboxymethyl chitosan; The preparation method of the moistening boric acid eye drops comprises the following steps: S1. Add boric acid, chlorhexidine gluconate solution and calcium disodium ethylenediaminetetraacetate into water and stir evenly at 60-70° C. to obtain a boric acid complex; S2, adding sodium hyaluronate and sodium alginate into water and stirring for 1-5 hours, adding hydroxypropyl methylcellulose, stirring at 30-40° C. for 10-30 minutes, to obtain a hydroxypropyl methylcellulose complex; S3, adding soybean lecithin, cholesterol and ethylparaben to chloroform and stirring evenly to obtain phase A; Add collagen and carboxymethyl chitosan to the citric acid aqueous solution and stir evenly to obtain phase B; Add phase A to phase B under stirring, treat with ultrasound for 1-2h, remove chloroform by vacuum rotary evaporation at 50-60°C, add citric acid aqueous solution for hydration, treat with ultrasound for 1-5min, and filter to obtain liposomes; S4. Evenly mix the boric acid complex, hydroxypropyl methylcellulose complex and liposome, and adjust the pH value of the system to 6.5-7.

5.

2. The moistening boric acid eye drops according to claim 1, characterized in that: The molecular weight of collagen is 2-5 kDa.

3. A method for preparing the moistening boric acid eye drops as claimed in claim 1 or 2, characterized in that: The steps include: S1. Add boric acid, chlorhexidine gluconate solution and calcium disodium ethylenediaminetetraacetate into water and stir evenly at 60-70° C. to obtain a boric acid complex; S2, adding sodium hyaluronate and sodium alginate into water and stirring for 1-5 hours, adding hydroxypropyl methylcellulose, stirring at 30-40° C. for 10-30 minutes, to obtain a hydroxypropyl methylcellulose complex; S3, adding soybean lecithin, cholesterol and ethyl paraben to chloroform and stirring evenly to obtain phase A; Add collagen and carboxymethyl chitosan to the citric acid aqueous solution and stir evenly to obtain phase B; Add phase A to phase B under stirring, treat with ultrasound for 1-2h, remove chloroform by vacuum rotary evaporation at 50-60°C, add citric acid aqueous solution for hydration, treat with ultrasound for 1-5min, and filter to obtain liposomes; S4. Evenly mix the boric acid complex, hydroxypropyl methylcellulose complex and liposome, and adjust the pH value of the system to 6.5-7.

5.

4. The method for preparing the moistening boric acid eye drops according to claim 3, characterized in that: In S1, the mass fraction of the chlorhexidine gluconate solution is 20±2%.

5. The method for preparing the moistening boric acid eye drops according to claim 3, characterized in that: In S3, the pH value of the citric acid aqueous solution is 4.6-4.

8.

6. The method for preparing the moistening boric acid eye drops according to claim 3, characterized in that: In S3, the ultrasound frequency is 20-25kHz.

7. The method for preparing the moistening boric acid eye drops according to claim 3, characterized in that: In S3, 220 nm filter membrane was used for filtration.

8. The method for preparing the moistening boric acid eye drops according to claim 3, characterized in that: In S3, a sodium hydroxide solution with a concentration of 0.1-0.5 mol / L is used to adjust the pH value of the system to 6.5-7.5.

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