Sodium hyaluronate eye drops and preparation method thereof

Abstract

The invention relates to the technical field of pharmaceutical preparations, and particularly discloses sodium hyaluronate eye drops and a preparation method thereof. The preparation method of the sodium hyaluronate eye drops comprises the following steps: adding sodium chloride, potassium chloride, aminocaproic acid and edetate disodium according to the prescription dosage into water for injection which is 40-65% of the total volume, and adjusting the pH value to weak acidity to obtain a first solution; the preparation method comprises the following steps: dispersing sodium hyaluronate in a prescription dosage into a part of water for injection at 25-35 DEG C to obtain a first liquid medicine with the mass concentration of sodium hyaluronate being less than 2%; and adding the first liquid medicine into the first solution at 25-35 DEG C, then adding the residual water for injection, filtering, filling, carrying out leak detection, and carrying out light detection to obtain the sodium hyaluronate eye drops. The preparation method provided by the invention can obviously improve the production efficiency, is convenient to realize industrial production, has a wide application prospect, and provides a new idea for preparation of the sodium hyaluronate eye drops.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical preparation technology, and in particular to a sodium hyaluronate eye drop and its preparation method. Background Technology

[0002] In ophthalmological clinics, dry eye syndrome and corneal and conjunctival epithelial damage caused by internal and external factors are highly prevalent, seriously affecting patients' vision and quality of life. Dry eye syndrome is caused by insufficient tear secretion, rapid evaporation, or abnormal composition, leading to instability and reduced volume of the anterior tear film on the cornea, resulting in dry eyes, foreign body sensation, and even epithelial defects. Corneal and conjunctival epithelial damage can be induced by internal factors (such as Sjögren's syndrome, Sjögren's syndrome, and dry eye syndrome causing tear abnormalities) or external factors (such as ophthalmic surgery, drug irritation, trauma, and long-term contact lens wear). Current treatment focuses on restoring tear film stability, hydration, and promoting epithelial repair. Artificial tears are a basic approach, but traditional products only provide hydration. They differ greatly from natural tear mucins in structure, molecular weight, and rheological properties, resulting in short residence time on the ocular surface, easy loss, frequent instillation, increased burden on patients, and potential irritation to the ocular surface. Hyaluronic acid is a key research area due to its unique properties: its structure and molecular weight are highly similar to mucin, it has strong viscoelasticity, and its sodium salt (sodium hyaluronate) forms a stable moisture film on the ocular surface that is not easily washed away; its strong water-binding capacity provides long-lasting hydration and creates an environment conducive to epithelial repair. Currently, the preparation of sodium hyaluronate eye drops still faces many challenges, such as long preparation time, low viscosity, and unacceptable molecular weight. Therefore, providing a sodium hyaluronate eye drop solution and its preparation method is of great significance in solving these problems. Summary of the Invention

[0003] In view of this, the present invention provides a sodium hyaluronate eye drop and a method for preparing the same.

[0004] To solve the above-mentioned technical problems, the technical solution provided by the present invention is as follows: The first aspect of this invention provides a method for preparing sodium hyaluronate eye drops, comprising the following steps: Step a: Add the prescribed amounts of sodium chloride, potassium chloride, aminocaproic acid, and disodium edetate to a total volume of 40-65% water for injection, and adjust the pH to weakly acidic to obtain the first solution; Step b: At 25~35℃, the prescribed amount of sodium hyaluronate is dispersed into a portion of water for injection to obtain a first solution with a sodium hyaluronate mass concentration of <2%; Step c: Add the first drug solution to the first solution at 25~35℃, then add the remaining water for injection, filter, fill, check for leaks, and inspect with a light to obtain sodium hyaluronate eye drops.

[0005] Currently, the existing methods for preparing sodium hyaluronate eye drops mainly involve adding the active ingredient to water to absorb water and swell before completely dissolving it. However, this method prolongs the production and preparation time and may lead to problems such as degradation of the active ingredient. Secondly, the inventors discovered during their research that the viscosity and molecular weight of sodium hyaluronate eye drops prepared by the existing methods are reduced, which cannot guarantee product quality. Therefore, there is an urgent need to provide a sodium hyaluronate eye drop and its preparation method.

[0006] Through extensive experimentation, the inventors discovered that preparing the first solution separately—that is, preparing sodium hyaluronate separately—solves problems encountered when directly adding sodium hyaluronate, such as poor solubility, long stirring times leading to molecular chain breakage, and reduced viscosity and molecular weight. Preparing sodium hyaluronate separately significantly improves the viscosity and molecular weight of sodium hyaluronate eye drops, thereby improving product quality and saving production preparation time. Furthermore, by limiting the dispersion concentration of sodium hyaluronate in the first solution, not only can product quality be further improved, but dissolution time is also significantly reduced, increasing production preparation efficiency. Experiments have shown that when the dispersion concentration is too high, stirring becomes difficult, and the resulting first solution may not dissolve completely.

[0007] During the experiment, the inventors discovered that sodium hyaluronate eye drops are temperature-sensitive. Therefore, they further limited the preparation temperature of the first drug solution and the mixing temperature of the first drug solution and the first solution during the preparation process to further improve the viscosity and molecular weight of sodium hyaluronate eye drops, thereby improving the product quality of sodium hyaluronate eye drops, which is of great significance for improving the safety of patients taking the medication.

[0008] Preferably, in step a, the weak acidity refers to a pH of 6.3 to 6.7.

[0009] It should be further explained that in step b, when dispersing the prescribed amount of sodium hyaluronate into water for injection, it is necessary to add it while stirring, so that the sodium hyaluronate is dispersed in the water as a transparent mixture.

[0010] Preferably, in step c, the filtration uses a multi-stage polyethersulfone filter element.

[0011] It should be further noted that in step c, the multi-stage polyethersulfone filter element is a three-stage polyethersulfone filter element, wherein the pore size of the first-stage polyethersulfone filter element is 0.45μm, and the pore sizes of the second-stage and third-stage polyethersulfone filter elements are both 0.2μm.

[0012] The optimized membrane filtration not only improves the stability of sodium hyaluronate eye drops, but also further improves production efficiency, reduces production costs, and facilitates industrial production.

[0013] For example, in step c, the filling conditions are: filling sodium hyaluronate eye drops into a low-density polyethylene single-dose eye drop bottle.

[0014] Preferably, in step c, the filling process uses an integrated blow-fill-seal equipment, the temperature of the filling machine mold is 180~220℃, and the filling rate is 25000~30000 bottles / h.

[0015] During the research process, the inventors further discovered that the temperature of the filling machine mold and the filling speed further affect the viscosity and molecular weight of sodium hyaluronate eye drops, and the optimized parameters are conducive to further improving product quality.

[0016] Preferably, in step c, the leak detection is performed using a high-voltage discharge leak detection method.

[0017] It should be further explained that in step c, the leak detection conditions are as follows: before leak detection, the leak detector is confirmed with a positive sample with a 5μm pore size, and then the product sealing test is performed. The formula is sodium hyaluronate eye drops; the set voltage is 77.27%; the defective product threshold is 900 for station 1, 950 for station 2, 700 for station 3, and 800 for station 4.

[0018] Station 1 inspects the bottle head, station 2 inspects the bottle neck, station 3 inspects the bottle body, and station 4 inspects the bottle bottom.

[0019] This invention abandons the traditional manual inspection and color water leak detection methods for sealing tests. It uses a high-voltage discharge leak detection method, which can accurately reject leaking products without affecting product quality.

[0020] Preferably, in step c, the light intensity of the lamp inspection is 2000 lx to 3000 lx.

[0021] It should be further explained that in step c, after the light inspection is completed, the qualified products are covered with an opaque aluminum bag.

[0022] A second aspect of the present invention provides a sodium hyaluronate eye drop, which is prepared by the above-described method for preparing sodium hyaluronate eye drops.

[0023] The third aspect of the present invention provides the above-mentioned sodium hyaluronate eye drops, wherein each 1 mL of sodium hyaluronate eye drops comprises: 1-3 mg of sodium hyaluronate, 5-8 mg of sodium chloride, 1-2 mg of potassium chloride, 1-3 mg of aminocaproic acid and 0.05-0.2 mg of disodium edetate.

[0024] The preparation method of sodium hyaluronate eye drops provided by this invention improves production efficiency to a certain extent, facilitates industrial production, and has broad application prospects. Moreover, the sodium hyaluronate eye drops prepared by the preparation method provided by this invention have suitable viscosity and molecular weight, and have good product quality, providing a new approach for the preparation of sodium hyaluronate eye drops. Detailed Implementation

[0025] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.

[0026] To better illustrate the present invention, further examples are provided below.

[0027] Example 1 This embodiment provides a sodium hyaluronate eye drop solution, wherein each 1 mL of sodium hyaluronate eye drop solution comprises: 3 mg sodium hyaluronate, 5 mg sodium chloride, 2 mg potassium chloride, 1 mg aminocaproic acid and 0.05 mg disodium edetate; This embodiment also provides a method for preparing the above-mentioned sodium hyaluronate eye drops, including the following steps: Step a: Add the prescribed amounts of sodium chloride, potassium chloride, aminocaproic acid, and disodium edetate to a total volume of 65% water for injection, and adjust the pH to 6.3 using sodium hydroxide to obtain the first solution; Step b: At 25°C, disperse the prescribed amount of sodium hyaluronate into water for injection until the mass concentration of sodium hyaluronate is 1.5%. Stir while adding the solution to disperse the sodium hyaluronate into the water to form a transparent mixture, thus obtaining the first solution. Step c: Add the first drug solution to the first solution at 25°C, then add the remaining water for injection, and then pass it through a three-stage polyethersulfone filter. The pore size of the first-stage polyethersulfone filter is 0.45μm, and the pore sizes of the second-stage and third-stage polyethersulfone filters are both 0.2μm. Fill the sodium hyaluronate eye drops into low-density polyethylene single-dose eye drop bottles. Filling is done using a blow-fill-seal integrated equipment. The temperature of the filling machine mold is 220°C, and the filling rate is 25,000 bottles / h. Leak detection is performed using a high-voltage discharge leak detection method. The leak detection conditions are: set voltage: 77.27%; defect threshold: station 1: 900, station 2: 950, station 3: 700, station 4: 800. Leakage judgment criteria: leakage is defined as when the light intensity exceeds the defective product threshold; during light inspection, the light intensity is controlled at 2000 lx. After the light inspection, qualified products are covered with opaque aluminum bags to obtain sodium hyaluronate eye drops.

[0028] Example 2 This embodiment provides a sodium hyaluronate eye drop solution, wherein each 1 mL of sodium hyaluronate eye drop solution comprises: 1 mg sodium hyaluronate, 8 mg sodium chloride, 1 mg potassium chloride, 2 mg aminocaproic acid and 0.1 mg disodium edetate; This embodiment also provides a method for preparing the above-mentioned sodium hyaluronate eye drops, including the following steps: Step a: Add the prescribed amounts of sodium chloride, potassium chloride, aminocaproic acid, and disodium edetate to a 40% volume of water for injection. Adjust the pH to 6.7 using sodium hydroxide to obtain the first solution. Step b: At 35°C, disperse the prescribed amount of sodium hyaluronate into water for injection until the mass concentration of sodium hyaluronate is 1.8%. Stir while adding the solution to disperse the sodium hyaluronate into the water to form a transparent mixture, thus obtaining the first solution. Step c: Add the first drug solution to the first solution at 35°C, then add the remaining water for injection, and then pass it through a three-stage polyethersulfone filter. The pore size of the first-stage polyethersulfone filter is 0.45μm, and the pore sizes of the second-stage and third-stage polyethersulfone filters are both 0.2μm. Fill the sodium hyaluronate eye drops into low-density polyethylene single-dose eye drop bottles. Filling is done using a blow-fill-seal integrated equipment. The temperature of the filling machine mold is 180°C, and the filling rate is 30,000 bottles / h. Leak detection is performed using a high-voltage discharge leak detection method. The leak detection conditions are: set voltage: 77.27%; defect threshold: station 1: 900, station 2: 950, station 3: 700, station 4: 800. Leakage judgment criteria: leakage occurs when the light intensity exceeds the defective product threshold; during light inspection, the light intensity is controlled at 3000 lx. After the light inspection, qualified products are covered with opaque aluminum bags to obtain sodium hyaluronate eye drops.

[0029] Example 3 This embodiment provides a sodium hyaluronate eye drop solution, wherein each 1 mL of sodium hyaluronate eye drop solution comprises: 2 mg sodium hyaluronate, 6 mg sodium chloride, 1 mg potassium chloride, 2 mg aminocaproic acid and 0.15 mg disodium edetate; This embodiment also provides a method for preparing the above-mentioned sodium hyaluronate eye drops, including the following steps: Step a: Add the prescribed amounts of sodium chloride, potassium chloride, aminocaproic acid, and disodium edetate to a 50% volume of water for injection. Adjust the pH to 6.5 using sodium hydroxide to obtain the first solution. Step b: At 30°C, disperse the prescribed amount of sodium hyaluronate into water for injection until the mass concentration of sodium hyaluronate is 1%. Stir while adding the solution to disperse the sodium hyaluronate into a transparent mixture in the water, thus obtaining the first solution. Step c: Add the first drug solution to the first solution at 30°C, then add the remaining water for injection, and then pass it through a three-stage polyethersulfone filter. The pore size of the first-stage polyethersulfone filter is 0.45μm, and the pore sizes of the second-stage and third-stage polyethersulfone filters are both 0.2μm. Fill the sodium hyaluronate eye drops into low-density polyethylene single-dose eye drop bottles. Filling is done using a blow-fill-seal integrated equipment. The temperature of the filling machine mold is 200°C, and the filling rate is 30,000 bottles / h. Leak detection is performed using a high-voltage discharge leak detection method. The leak detection conditions are: set voltage: 77.27%; defect threshold: station 1: 900, station 2: 950, station 3: 700, station 4: 800. Leakage judgment criteria: leakage is defined as when the light intensity exceeds the defective product threshold; during light inspection, the light intensity is controlled at 2500 lx. After the light inspection, qualified products are covered with opaque aluminum bags to obtain sodium hyaluronate eye drops.

[0030] Comparative Example 1 This comparative example provides a sodium hyaluronate eye drop solution, wherein each 1 mL of sodium hyaluronate eye drop solution comprises: 3 mg sodium hyaluronate, 5 mg sodium chloride, 2 mg potassium chloride, 1 mg aminocaproic acid and 0.05 mg disodium edetate; This comparative example also provides a method for preparing the above-mentioned sodium hyaluronate eye drops. Compared with Example 1, the difference lies in increasing the preparation temperature, specifically including the following steps: Step a: Add the prescribed amounts of sodium chloride, potassium chloride, aminocaproic acid, and disodium edetate to a total volume of 65% water for injection, and adjust the pH to 6.3 using sodium hydroxide to obtain the first solution; Step b: At 55°C, disperse the prescribed amount of sodium hyaluronate into water for injection until the mass concentration of sodium hyaluronate is 1.5%. Stir while adding the solution to disperse the sodium hyaluronate into the water to form a transparent mixture, thus obtaining the first solution. Step c: Add the first drug solution to the first solution at 55°C, then add the remaining water for injection, and then pass it through a three-stage polyethersulfone filter. The first-stage polyethersulfone filter has a pore size of 0.45μm, and the second and third-stage polyethersulfone filters both have a pore size of 0.2μm. Fill the sodium hyaluronate eye drops into low-density polyethylene single-dose eye drop bottles using a blow-fill-seal integrated equipment. The temperature of the filling machine mold is 220°C, and the filling rate is 25,000 bottles / h. Leak detection is performed using a high-voltage discharge leak detection method. The leak detection conditions are: set voltage: 77.27%; defect threshold: station 1: 900, station 2: 950, station 3: 700, station 4: 800. Leakage judgment criteria: leakage is defined as when the light intensity exceeds the defective product threshold; during light inspection, the light intensity is controlled at 2000 lx. After the light inspection, qualified products are covered with opaque aluminum bags to obtain sodium hyaluronate eye drops.

[0031] Comparative Example 2 This comparative example provides a sodium hyaluronate eye drop solution, wherein each 1 mL of sodium hyaluronate eye drop solution comprises: 3 mg sodium hyaluronate, 5 mg sodium chloride, 2 mg potassium chloride, 1 mg aminocaproic acid and 0.05 mg disodium edetate; This comparative example also provides a method for preparing the above-mentioned sodium hyaluronate eye drops. Compared with Example 1, the difference lies in the change of preparation conditions, specifically including the following steps: Step a: Add 80% of the total volume of water for injection, cool it to below 25°C, add the prescribed amount of sodium hyaluronate, stir to disperse and dissolve, then add sodium chloride, potassium chloride, aminocaproic acid and disodium edetate in sequence, stir to dissolve, and adjust the pH to 6.3 with sodium hydroxide. Step b: Add the first drug solution to the first solution at 25°C, then add the remaining water for injection, and then pass it through a three-stage polyethersulfone filter. The pore size of the first-stage polyethersulfone filter is 0.45μm, and the pore sizes of the second-stage and third-stage polyethersulfone filters are both 0.2μm. Fill the sodium hyaluronate eye drops into low-density polyethylene single-dose eye drop bottles using a blow-fill-seal integrated equipment. The temperature of the filling machine mold is 220°C, and the filling rate is 25,000 bottles / h. Leak detection is performed using a high-voltage discharge leak detection method. The leak detection conditions are: set voltage: 77.27%; defect threshold: station 1: 900, station 2: 950, station 3: 700, station 4: 800. Leakage judgment criteria: leakage is defined as when the light intensity exceeds the defective product threshold; during light inspection, the light intensity is controlled at 2000 lx. After the light inspection, qualified products are covered with opaque aluminum bags to obtain sodium hyaluronate eye drops.

[0032] Comparative Example 3 This comparative example provides a sodium hyaluronate eye drop solution, wherein each 1 mL of sodium hyaluronate eye drop solution comprises: 3 mg sodium hyaluronate, 5 mg sodium chloride, 2 mg potassium chloride, 1 mg aminocaproic acid and 0.05 mg disodium edetate; This comparative example also provides a method for preparing the above-mentioned sodium hyaluronate eye drops. Compared with Example 1, the difference lies in increasing the dispersion concentration of the first solution, specifically including the following steps: Step a: Add the prescribed amounts of sodium chloride, potassium chloride, aminocaproic acid, and disodium edetate to a total volume of 65% water for injection, and adjust the pH to 6.3 using sodium hydroxide to obtain the first solution; Step b: At 25°C, disperse the prescribed amount of sodium hyaluronate into water for injection until the mass concentration of sodium hyaluronate is 3%. Stir while adding the solution to disperse the sodium hyaluronate into a transparent mixture in the water, thus obtaining the first solution. Step c: Add the first drug solution to the first solution at 25°C, then add the remaining water for injection, and then pass it through a three-stage polyethersulfone filter. The pore size of the first-stage polyethersulfone filter is 0.45μm, and the pore sizes of the second-stage and third-stage polyethersulfone filters are both 0.2μm. Fill the sodium hyaluronate eye drops into low-density polyethylene single-dose eye drop bottles using a blow-fill-seal integrated equipment. The temperature of the filling machine mold is 220°C, and the filling rate is 25,000 bottles / h. Leak detection is performed using a high-voltage discharge leak detection method. The leak detection conditions are: set voltage: 77.27%; defect threshold: station 1: 900, station 2: 950, station 3: 700, station 4: 800. Leakage judgment criteria: leakage is defined as when the light intensity exceeds the defective product threshold; during light inspection, the light intensity is controlled at 2000 lx. After the light inspection, qualified products are covered with opaque aluminum bags to obtain sodium hyaluronate eye drops.

[0033] Quality Inspection The kinematic viscosity, molecular weight and total preparation time of the sodium hyaluronate eye drops provided in Examples 1-3 and Comparative Examples 1-3 were tested, and the results are shown in Table 1.

[0034] The detection methods are as follows: Kinematic viscosity: Take this product and determine its kinematic viscosity at 30±0.1℃ according to the viscosity determination method (Chinese Pharmacopoeia 2020 Edition, Part IV, General Chapter 0633, Method I).

[0035] Molecular weight and molecular weight distribution: determined by size exclusion chromatography (Chinese Pharmacopoeia 2020 edition, Part IV, General Chapter 0514).

[0036] Take an appropriate amount of this product (approximately equivalent to 1 mg of sodium hyaluronate) and place it in a 10 mL volumetric flask. Dilute to the mark with the mobile phase and shake well.

[0037] For each series of reference solutions, take appropriate amounts of 4-5 sodium polystyrene sulfonate reference standards with known molecular weights ranging from 10,000 to 5,000,000, dissolve them in the mobile phase, and quantitatively dilute them to prepare solutions containing approximately 0.1 mg per 1 mL.

[0038] Chromatographic conditions: Polyhydroxymethacrylate (PHM) was used as the stationary phase (Shodex SB-806HQ, 8.0 mm × 300 mm or other equivalent column); 0.2 mol / L sodium chloride solution (11.9 g of sodium chloride dissolved in water and diluted to 1000 mL) was used as the mobile phase; a differential refractive index detector was used at 35 °C; the flow rate was 0.6 mL / min; the column temperature was 35 °C; and the injection volume was 100 μL.

[0039] For the assay, inject a series of reference solutions and test solutions into the liquid chromatograph and record the chromatograms.

[0040] The linear regression equation and the molecular weight and molecular weight distribution of the test sample were calculated using GPC software with universal correction. The K value for the reference standard was 0.00018 and the α value was 0.65; the K value for this product was 0.00057 and the α value was 0.75.

[0041] The weight-average molecular weight (Mw) of this product should not be less than 400,000, and the distribution width (Mw / Mn) should be less than 3.0.

[0042] Table 1

[0043] Due to the properties of sodium hyaluronate, the kinematic viscosity of sodium hyaluronate eye drops with equal concentrations is not proportional. A 0.1% concentration sodium hyaluronate eye drop (i.e., a sodium hyaluronate content of 1 mg / mL) should have a kinematic viscosity of 3-4 (mm). 2 The kinematic viscosity of 0.3% sodium hyaluronate eye drops (i.e., sodium hyaluronate content of 3 mg / mL) should be 17~30 mm / s. 2 / s. Therefore, the kinematic viscosity varies considerably depending on the concentration. However, within the specified range for sodium hyaluronate eye drops of a particular concentration, a higher kinematic viscosity is better.

[0044] The experimental data above show that, compared with Comparative Examples 1-3, the sodium hyaluronate eye drops prepared in Examples 1-3 of this invention, when prepared using the fractional feeding method at 25-35℃, have a higher weight-average molecular weight, a narrower distribution width, and a higher kinematic viscosity at the corresponding concentration. Furthermore, the preparation time is shorter, saving production time and increasing production efficiency while ensuring product quality. The sodium hyaluronate eye drops prepared in these embodiments of the invention exhibit better stability and safety, thus improving the safety of clinical applications.

[0045] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions or improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for preparing sodium hyaluronate eye drops, characterized in that, Includes the following steps: Step a: Add the prescribed amounts of sodium chloride, potassium chloride, aminocaproic acid, and disodium edetate to a total volume of 40-65% water for injection, and adjust the pH to weakly acidic to obtain the first solution; Step b: At 25~35℃, the prescribed amount of sodium hyaluronate is dispersed into a portion of water for injection to obtain a first solution with a sodium hyaluronate mass concentration of <2%; Step c: Add the first drug solution to the first solution at 25~35℃, then add the remaining water for injection, filter, fill, check for leaks, and inspect with a light to obtain sodium hyaluronate eye drops.

2. The method for preparing sodium hyaluronate eye drops as described in claim 1, characterized in that, In step a, the weak acidity refers to a pH of 6.3 to 6.

7.

3. The method for preparing sodium hyaluronate eye drops as described in claim 1, characterized in that, In step c, the filtration uses a multi-stage polyethersulfone filter cartridge.

4. The method for preparing sodium hyaluronate eye drops as described in claim 3, characterized in that, In step c, the multi-stage polyethersulfone filter element is a three-stage polyethersulfone filter element, wherein the pore size of the first-stage polyethersulfone filter element is 0.45μm, and the pore sizes of the second-stage and third-stage polyethersulfone filter elements are both 0.2μm.

5. The method for preparing sodium hyaluronate eye drops as described in claim 1, characterized in that, In step c, the filling process uses an integrated blow-fill-seal equipment, with the temperature of the filling machine mold being 180~220℃ and the filling rate being 25000~30000 bottles / h.

6. The method for preparing sodium hyaluronate eye drops as described in claim 1, characterized in that, In step c, the leak detection is performed using the high-voltage discharge leak detection method.

7. The method for preparing sodium hyaluronate eye drops as described in claim 1, characterized in that, In step c, the illumination intensity of the lamp inspection is 2000 lx to 3000 lx.

8. A sodium hyaluronate eye drop, characterized in that, It is prepared by the method for preparing sodium hyaluronate eye drops as described in any one of claims 1 to 7.

9. The sodium hyaluronate eye drops as described in claim 8, characterized in that, Each 1 mL of sodium hyaluronate eye drops contains: 1-3 mg sodium hyaluronate, 5-8 mg sodium chloride, 1-2 mg potassium chloride, 1-3 mg aminocaproic acid, and 0.05-0.2 mg disodium edetate.

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