Preparation process of sodium hyaluronate eye drops

Abstract

The preparation process of the sodium hyaluronate eye drops comprises the following steps: S1, firstly adding water for injection under a sterile condition, then sequentially adding sodium chloride, potassium chloride, boric acid, borax, glycerol and benzalkonium chloride, and stirring by a high-shear stirrer to form a solution A; s2, under a sterile condition, firstly adding water for injection, then adding modified sodium hyaluronate, and stirring by a high-shear stirrer to form a solution B; s3, adding the solution B into the solution A under a sterile condition, and stirring by using a high-shear stirrer; s4, adding the residual water for injection, and stirring by a high-shear stirrer to obtain the sodium hyaluronate eye drops; s5, filtering through a sterile filter of 0.22 [mu] m; and S6, sub-packaging into single-dose packaging containers under sterile filling equipment, and sealing the single-dose packaging containers. According to the preparation process of the sodium hyaluronate eye drops, the preservative is introduced, and the sterile preparation technology, sterile filtration and single-dose packaging are adopted, so that the safety is improved, the concentration of the sodium hyaluronate is increased, the glycerol is added, and the use experience of a patient is improved.

Description

Technical Field

[0001] The present invention belongs to the field of pharmaceutical preparation, and particularly relates to a preparation process of sodium hyaluronate eye drops. Background Art

[0002] With the development of society, great changes have taken place in people's lifestyle and working environment, and the incidence of ophthalmic diseases has been increasing year by year. In recent years, various factors such as population aging, lifestyle changes, increased work intensity, increased allergens, and improper eye use have led to the increasing incidence of various eye diseases such as eye infections, keratoconjunctivitis, dry eye, corneal injury ulcers, video terminal syndrome, cataracts, and glaucoma, which also promotes the relatively rapid growth of the ophthalmic drug market.

[0003] Among them, dry eye is a common ophthalmic disease, mainly due to damage to the corneal and conjunctival epithelium caused by local eye diseases or systemic diseases, accompanied by abnormal quality and quantity of the tear film layer. Its symptoms include eye pain, photophobia, foreign body sensation, dryness, tearing, etc. Objective examinations will show positive fluorescein staining and rose bengal staining, shortened tear film break-up time, and reduced tear secretion.

[0004] Sodium hyaluronate, also known as hyaluronic acid sodium, is an acidic mucopolysaccharide macromolecule obtained by cockscomb extraction method or microbial fermentation method, and is widely present in the vitreous humor, aqueous humor, skin, joint synovial fluid, umbilical cord, etc. in the human body, playing roles such as lubrication, water retention, buffering, viscoelasticity, wound repair, network fixation, and cell regulation.

[0005] Sodium hyaluronate eye drops are mainly used for the treatment of dry eye and corneal epithelial defects. It can effectively supplement tears, relieve the symptoms of dry eyes, and at the same time has the function of repairing defective epithelial cells. When dry eye occurs, the corneal epithelium is prone to be unhealthy or even defective. Instilling sodium hyaluronate eye drops can accelerate the rapid healing of corneal epithelial cells while relieving dryness.

[0006] Existing sodium hyaluronate eye drops have the following problems: (1) Short residence time: The existing sodium hyaluronate eye drops have a short residence time in the patient's eye. In order to improve the comfort and treatment effect of the patient's eyes, frequent instillation is required. However, due to the work or life restrictions of different patients, it is often impossible to instill frequently, resulting in the symptoms such as dry eyes of the patient not being fully relieved.

[0007] (2) Inconvenient packaging use: There are many inconveniences in the use of multi-dose packaging. Each time it is opened, the risk of being contaminated is increased, and it is not convenient to carry.

[0008] Therefore, it is extremely necessary to develop a preparation process for sodium hyaluronate eye drops that can effectively solve the problems of existing sodium hyaluronate eye drops, prolong the residence time of the drug in the eye, reduce the risk of microbial contamination, and improve the safety and stability of the product. At the same time, the operation process is simple and easy to use, which has important practical significance. Summary of the invention

[0009] Purpose of the invention: In order to overcome the above shortcomings, the purpose of the present invention is to provide a preparation process for sodium hyaluronate eye drops, which has a reasonable design, introduces preservatives, adopts aseptic preparation technology and aseptic filtration and single-dose packaging, improves the safety of the product, increases the concentration of sodium hyaluronate and adds glycerol, improves the patient's use experience, and uses high shear mixing technology and freeze-drying process to improve the stability and quality of the product, and has broad application prospects.

[0010] The objective of the present invention is achieved through the following technical solutions: A preparation process of sodium hyaluronate eye drops comprises the following steps: S1: Under aseptic conditions, use a sterilized preparation container; first add 50-70% of the process amount of water for injection, and then add the process amount of sodium chloride, potassium chloride, boric acid, borax, glycerol and benzalkonium chloride in sequence; use a high shear mixer to stir until completely dissolved to form a uniform solution A; S2: Under aseptic conditions, use another sterilized preparation container; first add 20-25% of the process amount of water for injection, and then add the process amount of modified sodium hyaluronate; use a high shear stirrer to stir until the modified sodium hyaluronate is completely dissolved to form a uniform solution B; S3: Under sterile conditions, slowly add solution B to solution A while continuously stirring with a high shear stirrer until a uniform and transparent mixed solution is obtained; S4: Add the remaining amount of water for injection used in the process, stir with a high shear stirrer, and mix thoroughly to obtain sodium hyaluronate eye drops; S5: filtering the sodium hyaluronate eye drops through a 0.22 μm sterile filter; S6: packaging the filtered sodium hyaluronate eye drops into sterilized single-dose packaging containers under aseptic filling equipment; and sealing the packaged containers.

[0011] The preparation process of the sodium hyaluronate eye drops of the present invention strictly adopts aseptic operation in the entire preparation process, and introduces 0.22 μm aseptic filtration in the final product. The aseptic preparation technology and aseptic filtration can ensure the sterility of the product to the greatest extent, reduce the risk of microbial contamination, and ensure the safety of patient use.

[0012] During the dissolution and mixing process, a high-shear stirrer is used. High-shear mixing can more effectively disperse and dissolve each component, making the viscosity and uniformity of the eye drops better, and the stability higher.

[0013] The eye drops are filled into single-dose packages. Single-dose packages can avoid the risk of contamination caused by multiple openings, ensure the sterility of each use, facilitate the patient to carry and use, and improve the safety and compliance of medication.

[0014] In addition, benzalkonium chloride is added as a preservative, which can effectively prevent microbial contamination of the product during storage and use, extend the shelf life of the product, and ensure the safety of multiple uses. Even with single-dose packaging, the presence of the preservative can increase the stability of the product and provide additional protection.

[0015] In addition, glycerol is added. Glycerol has good moisturizing and lubricating effects, can increase the viscosity of the eye drops, extend the residence time on the ocular surface, improve the lubrication of the eyes, relieve dry eye symptoms, enhance the comfort of patients, and reduce the dropping frequency.

[0016] Furthermore, for the preparation process of the above-mentioned sodium hyaluronate eye drops, the preparation of the modified sodium hyaluronate includes the following steps: (1) Dissolve sodium hyaluronate in water for injection to prepare a 5 mg / ml sodium hyaluronate solution; (2) Add N-hydroxysuccinimide to the sodium hyaluronate solution and adjust the pH to 5.0 - 5.5; (3) Continue to add N-acetylcysteine to the sodium hyaluronate solution, adjust the pH to 4.5 - 5.0, and stir and react for 20 - 30 h; (4) Dialyze the sodium hyaluronate solution thoroughly with a 1% mass concentration hydrochloric acid solution; (5) Freeze-dry the dialyzed sodium hyaluronate solution to obtain modified sodium hyaluronate; (6) Store the prepared modified sodium hyaluronate under sterile conditions for standby.

[0017] Add N-hydroxysuccinimide to the sodium hyaluronate solution for carboxyl activation, then add N-acetylcysteine to introduce a mercapto group, dialyze thoroughly with a 1% mass concentration hydrochloric acid solution to remove the catalyst and impurities, and freeze-dry the dialyzed solution to ensure the activity and molecular weight of the modified sodium hyaluronate, ensure that its viscosity and functional characteristics are not affected, improve the dissolution rate, and facilitate the rapid preparation of subsequent preparations.

[0018] Furthermore, for the preparation process of the above-mentioned sodium hyaluronate eye drops, the molecular weight of the sodium hyaluronate is 1.3 million Da.

[0019] Further, in the preparation process of the above-mentioned sodium hyaluronate eye drops, the mass ratio of N-hydroxysuccinimide to sodium hyaluronate is 1 - 0.5:1, and the pH is adjusted to 5.0 at the same time.

[0020] Further, in the preparation process of the above-mentioned sodium hyaluronate eye drops, the mass ratio of N-acetylcysteine to sodium hyaluronate is 1 - 2:5.

[0021] Further, in the preparation process of the above-mentioned sodium hyaluronate eye drops, in S1, a high-shear stirrer is used for stirring, the stirring speed is 4500 - 5500 rpm, and the stirring time is 5 - 15 min until completely dissolved to form a uniform solution A.

[0022] Further, in the preparation process of the above-mentioned sodium hyaluronate eye drops, in S2, a high-shear stirrer is used for stirring, the stirring speed is 5500 - 6500 rpm, and the stirring time is 15 - 25 min until the modified sodium hyaluronate is completely dissolved to form a uniform solution B.

[0023] Further, in the preparation process of the above-mentioned sodium hyaluronate eye drops, in S3, continuous stirring is carried out with a high-shear stirrer, the stirring speed is 5500 - 6500 rpm, and the stirring time is 10 - 20 min until a uniform and transparent mixture is obtained.

[0024] Further, in the preparation process of the above-mentioned sodium hyaluronate eye drops, the material dosage of the above preparation process is as follows: 0.4 g of modified sodium hyaluronate, 5 g of sodium chloride, 0.5 g of potassium chloride, 0.2 g of boric acid, 0.01 g of borax, 3 - 5 g of glycerol (1% w / v), 0.01 - 0.05 g of benzalkonium chloride (0.01% w / v), and the injection water is added to 400 ml.

[0025] 0.01% w / v of benzalkonium chloride is added as a preservative in this prescription, which can effectively prevent the product from being contaminated by microorganisms during storage and use. 1% w / v of glycerol is added, which can increase the viscosity of the eye drops, prolong the residence time on the ocular surface, increase the dosage of the modified sodium hyaluronate, enhance its film-forming property and moisturizing property on the ocular surface, further prolong the residence time in the eye, improve the therapeutic effect, and reduce the number of drug administrations for patients.

[0026] Compared with the prior art, the present invention has the following beneficial effects: The preparation process of the sodium hyaluronate eye drops disclosed by the present invention is reasonably designed. By introducing preservatives, adopting aseptic preparation technology, aseptic filtration, and single-dose packaging, the sterility of the product is comprehensively improved, the risk of microbial contamination is reduced, and the safety of patients using the drug is ensured; by increasing the concentration of sodium hyaluronate and adding glycerol, the viscosity and moisturizing effect of the eye drops are improved, the residence time of the drug in the eye is prolonged, and the effect of relieving dry eye symptoms is enhanced; the increase in viscosity and lubricity makes patients feel more comfortable when using, reduces the foreign body sensation and irritation, and improves the medication compliance; the high-shear mixing technology and the optimized freeze-drying process ensure the uniformity and stability of the product, and guarantee the consistency of the quality of each batch of products; the single-dose packaging design is convenient for carrying and using, and avoids the contamination risk caused by multiple openings. Detailed implementation manners

[0027] Next, Comparative Example 1, Example 1, and Example 2 will be combined with specific experimental data to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts belong to the protection scope of the present invention. The following Comparative Example 1, Example 1, and Example 2 provide a preparation process of sodium hyaluronate eye drops.

[0028] Comparative Example 1 The preparation process of the sodium hyaluronate eye drops in Comparative Example 1 includes the following steps: S1: Under aseptic conditions, use a sterilized preparation container; first add 55% of the process dosage of injection water, and then sequentially add the process dosage of sodium chloride, potassium chloride, boric acid, borax, glycerol, and benzalkonium chloride; use a high-shear stirrer to stir, with a stirring speed of 4500 - 5500 rpm and a stirring time of 5 - 10 min until completely dissolved to form a uniform solution A; S2: Under aseptic conditions, use another sterilized preparation container; first add 25% of the process dosage of injection water, and then add the process dosage of sodium hyaluronate; use a high-shear stirrer to stir, with a stirring speed of 5500 - 6500 rpm and a stirring time of 15 - 20 min until the modified sodium hyaluronate is completely dissolved to form a uniform solution B; S3: Under aseptic conditions, slowly add solution B to solution A while continuously using a high-shear stirrer to stir, with a stirring speed of 5500 - 6500 rpm and a stirring time of 10 - 15 min until a uniform and transparent mixture is obtained; S4: Add the remaining process dosage of water for injection, stir using a high-shear stirrer, and after thorough mixing, the stirring speed is 4500 - 5500 rpm and the stirring time is 5 - 10 min to obtain sodium hyaluronate eye drops; S5: Filter the sodium hyaluronate eye drops through a 0.22 μm sterile filter to remove any possible microorganisms and particles; S6: Under aseptic filling equipment, dispense the filtered sodium hyaluronate eye drops into sterilized single-dose packaging containers; seal the filled containers to ensure asepticity.

[0029] The prescription of the sodium hyaluronate eye drops in Comparative Example 1 (per 400 ml of solution) is as follows: Sodium hyaluronate: 0.4 g Sodium chloride: 5 g Potassium chloride: 0.5 g Boric acid: 0.2 g Borax: 0.01 g Glycerol: 4 g (1% w / v) Benzalkonium chloride (preservative): 0.04 g (0.01% w / v) Water for injection: Add up to 400 ml Example 1 The preparation process of the sodium hyaluronate eye drops in Example 1 includes the following steps: (I) Preparation of modified sodium hyaluronate S1 Raw material preparation: Take sodium hyaluronate with a molecular weight of 1.3 million Da, dissolve it in water for injection, and prepare a 5 mg / ml sodium hyaluronate solution; S2 Carboxyl activation: Add N-hydroxysuccinimide to the above sodium hyaluronate solution, the mass ratio of N-hydroxysuccinimide to sodium hyaluronate is 0.5:1, and adjust the solution pH to 5.0; S3 Introduction of mercapto group: Add N-acetylcysteine, the mass ratio of N-acetylcysteine to sodium hyaluronate is 1:5, adjust the pH to 4.8, and stir and react for 24 h; S4 Dialysis purification: Conduct thorough dialysis using a 1% mass concentration hydrochloric acid solution to remove catalysts and impurities; S5 Freeze-drying: Freeze-dry the dialyzed solution to ensure that the activity and viscosity of the modified sodium hyaluronate are not affected and to improve the dissolution rate of the final product; S6 Aseptic treatment: Store the obtained modified sodium hyaluronate under aseptic conditions for standby.

[0030] (II) Preparation of sodium hyaluronate eye drops S1: Under aseptic conditions, use a sterilized preparation container; first add 55% of the process dosage of water for injection, and then sequentially add the sodium chloride, potassium chloride, boric acid, borax, glycerol, and benzalkonium chloride of the process dosage; stir using a high-shear stirrer at a stirring speed of 4500 - 5500 rpm for 5 - 10 min until completely dissolved to form a uniform solution A; S2: Under aseptic conditions, use another sterilized preparation container; first add 25% of the process dosage of water for injection, and then add the modified sodium hyaluronate of the process dosage; stir using a high-shear stirrer at a stirring speed of 5500 - 6500 rpm for 15 - 20 min until the modified sodium hyaluronate is completely dissolved to form a uniform solution B; S3: Under aseptic conditions, slowly add solution B to solution A while continuously stirring using a high-shear stirrer at a stirring speed of 5500 - 6500 rpm for 10 - 15 min until a uniform and transparent mixture is obtained; S4: Add the remaining process dosage of water for injection, stir using a high-shear stirrer, and after thorough mixing, stir at a stirring speed of 4500 - 5500 rpm for 5 - 10 min to prepare sodium hyaluronate eye drops; S5: Filter the sodium hyaluronate eye drops through a 0.22 μm sterile filter to remove any possible microorganisms and particles; S6: Under aseptic filling equipment, dispense the filtered sodium hyaluronate eye drops into sterilized single-dose packaging containers; seal the filled containers to ensure sterility.

[0031] The prescription of the sodium hyaluronate eye drops in Example 1 (per 400 ml of solution) is as follows: Modified sodium hyaluronate: 0.4 g Sodium chloride: 5 g Potassium chloride: 0.5 g Boric acid: 0.2 g Borax: 0.01 g Glycerol: 3 g (1% w / v) Benzalkonium chloride (preservative): 0.04 g (0.01% w / v) Water for injection: q.s. to 400 ml Example 2 The preparation process of the sodium hyaluronate eye drops in Example 2 includes the following steps: The preparation process of the sodium hyaluronate eye drops in Example 1 includes the following steps: (I) Preparation of modified sodium hyaluronate S1 Raw material preparation: Take sodium hyaluronate with a molecular weight of 1.3 million Da, dissolve it in water for injection, and prepare a sodium hyaluronate solution with a concentration of 5 mg / ml. S2 Carboxyl activation: Add N-hydroxysuccinimide to the above sodium hyaluronate solution. The mass ratio of N-hydroxysuccinimide to sodium hyaluronate is 0.5:1, and adjust the solution pH to 5.0. S3 Introduction of sulfhydryl group: Add N-acetylcysteine. The mass ratio of N-acetylcysteine to sodium hyaluronate is 1:5, adjust the pH to 4.8, and stir for 24 h. S4 Dialysis purification: Perform sufficient dialysis using a 1% hydrochloric acid solution to remove catalysts and impurities. S5 Freeze-drying: Freeze-dry the dialyzed solution to ensure that the activity and viscosity of the modified sodium hyaluronate are not affected and to improve the dissolution rate of the final product. S6 Sterile treatment: Store the obtained modified sodium hyaluronate under sterile conditions for standby.

[0032] (II) Preparation of sodium hyaluronate eye drops S1: Under sterile conditions, use a sterilized preparation container; first add 55% of the water for injection required by the process, and then sequentially add sodium chloride, potassium chloride, boric acid, borax, glycerol, and benzalkonium chloride required by the process; use a high-shear stirrer to stir at a stirring speed of 4500 - 5500 rpm for 5 - 10 min until completely dissolved to form a uniform solution A. S2: Under sterile conditions, use another sterilized preparation container; first add 25% of the water for injection required by the process, and then add the modified sodium hyaluronate required by the process; use a high-shear stirrer to stir at a stirring speed of 5500 - 6500 rpm for 15 - 20 min until the modified sodium hyaluronate is completely dissolved to form a uniform solution B. S3: Under sterile conditions, slowly add solution B to solution A while continuously using a high-shear stirrer to stir at a stirring speed of 5500 - 6500 rpm for 10 - 15 min until a uniform and transparent mixture is obtained. S4: Add the remaining water for injection required by the process, use a high-shear stirrer to stir, and after fully mixing evenly, stir at a stirring speed of 4500 - 5500 rpm for 5 - 10 min to prepare sodium hyaluronate eye drops. S5: Filter the sodium hyaluronate eye drops through a 0.22 μm sterile filter to remove possible microorganisms and particles. S6: Under a sterile filling device, dispense the filtered sodium hyaluronate eye drops into sterilized single-dose packaging containers; seal the filled containers to ensure sterility.

[0033] The prescription of sodium hyaluronate eye drops in Example 1 (per 400 ml of solution) is as follows: Modified sodium hyaluronate: 0.4 g Sodium chloride: 5 g Potassium chloride: 0.5 g Boric acid: 0.2 g Borax: 0.01 g Glycerol: 3 g (1% w / v) Benzalkonium chloride (preservative): 0.05 g (0.01% w / v) Water for injection: q.s. to 400 ml Effect verification Perform performance tests on the sodium hyaluronate eye drops prepared in Comparative Example 1, Example 1, and Example 2.

[0034] (1) pH value.

[0035] (2) Viscosity value.

[0036] (3) Bacteriostatic efficacy: The bacteriostatic efficacy was examined (determined by the method for examining bacteriostatic efficacy in General Chapter 1121 of the Fourth Part of the Chinese Pharmacopoeia 2020 Edition).

[0037] (4) Rat retention time experiment: The test method is as follows: Take 70 adult rats, randomly divide them into 7 groups with 10 rats in each group, and add the sodium hyaluronate eye drops prepared in Comparative Example 1, Example 1, and Example 2 into the eyes of each group of adult rats. Drop 1 drop into each rat's eye, and avoid the outflow of the eye drops after dropping. After 10 min, rinse the rat's eyeball with 10 ml of water for injection, collect the rinsing solution, and detect the content of sodium hyaluronate in the rinsing solution by high performance liquid chromatography. The average value of the detection values of 10 rats in each group is recorded as the final result.

[0038] The test results are shown in Table 1 and Table 2.

[0039] Table 1 Table 2 To sum up: The sodium hyaluronate eye drops (Example 1 and Example 2) prepared by the technical scheme of the present invention have increased the viscosity of the eye drops, prolonged the retention time of the eye drops in the eye, improved the lubrication of the eye, alleviated the dry eye symptoms, enhanced the comfort of the patients, reduced the dropping frequency, and made the patients feel more comfortable when using; the introduction of preservatives, the adoption of aseptic preparation technology and aseptic filtration, and single-dose packaging have improved the sterility of the product. Example 1, Example 2, and Comparative Example 1 have all reached the A standard, reducing the risk of microbial contamination and ensuring the safety of patients' medication.

[0040] The specific application ways of the present invention are numerous. The above description is only the preferred embodiment of the present invention. It should be noted that the above embodiments are only used to illustrate the present invention and do not limit the protection scope of the present invention. For those of ordinary skill in the art in this technical field, several improvements can be made without departing from the principle of the present invention, and these improvements should also be regarded as within the protection scope of the present invention.

Claims

1. A preparation process of sodium hyaluronate eye drops, characterized in that: The steps include: S1: Under aseptic conditions, use a sterilized preparation container; first add 50-70% of the process amount of water for injection, and then add the process amount of sodium chloride, potassium chloride, boric acid, borax, glycerol and benzalkonium chloride in sequence; use a high shear mixer to stir until completely dissolved to form a uniform solution A; S2: Under aseptic conditions, use another sterilized preparation container; first add 20-25% of the process amount of water for injection, and then add the process amount of modified sodium hyaluronate; Stirring with a high shear stirrer until the modified sodium hyaluronate is completely dissolved to form a uniform solution B; S3: Under sterile conditions, slowly add solution B to solution A while continuously stirring with a high shear stirrer until a uniform and transparent mixed solution is obtained; S4: Add the remaining amount of water for injection used in the process, stir with a high shear stirrer, and mix thoroughly to obtain sodium hyaluronate eye drops; S5: filtering the sodium hyaluronate eye drops through a 0.22 μm sterile filter; S6: packaging the filtered sodium hyaluronate eye drops into sterilized single-dose packaging containers under aseptic filling equipment; and sealing the packaged containers.

2. The preparation process of sodium hyaluronate eye drops according to claim 1, characterized in that: The preparation of the modified sodium hyaluronate comprises the following steps: (1) Dissolve sodium hyaluronate in water for injection to prepare a 5 mg / ml sodium hyaluronate solution; (2) adding N-hydroxysuccinimide to the sodium hyaluronate solution and adjusting the pH to 5.0-5.5; (3) Continue to add N-acetylcysteine ​​to the sodium hyaluronate solution, adjust the pH to 4.5-5.0, and stir the reaction for 20-30 hours; (4) Use 1% mass concentration hydrochloric acid solution to fully dialyze the sodium hyaluronate solution; (5) freeze-drying the dialyzed sodium hyaluronate solution to obtain modified sodium hyaluronate; (6) Store the prepared modified sodium hyaluronate under sterile conditions for future use.

3. The preparation process of sodium hyaluronate eye drops according to claim 2, characterized in that: The molecular weight of the sodium hyaluronate is 1.3 million Da.

4. The preparation process of sodium hyaluronate eye drops according to claim 2, characterized in that: The mass ratio of N-hydroxysuccinimide to sodium hyaluronate is 1-0.5:1, and the pH is adjusted to 5.

0.

5. The preparation process of sodium hyaluronate eye drops according to claim 2, characterized in that: The mass ratio of N-acetylcysteine ​​to sodium hyaluronate is 1-2:

5.

6. The preparation process of sodium hyaluronate eye drops according to claim 1, characterized in that: In the S1, a high shear stirrer is used for stirring at a stirring speed of 4500-5500 rpm for 5-15 min until the solution is completely dissolved to form a uniform solution A.

7. The preparation process of sodium hyaluronate eye drops according to claim 1, characterized in that: In the S2, a high shear stirrer is used for stirring at a stirring speed of 5500-6500 rpm for 15-25 min until the modified sodium hyaluronate is completely dissolved to form a uniform solution B.

8. The preparation process of sodium hyaluronate eye drops according to claim 1, characterized in that: In S3, the high shear stirrer is continuously used for stirring at a stirring speed of 5500-6500 rpm for a stirring time of 10-20 min until a uniform and transparent mixed solution is obtained.

9. The preparation process of the sodium hyaluronate eye drops according to any one of claims 1 to 8, characterized in that: The material dosages of the above preparation process are as follows: 0.4 g of modified sodium hyaluronate, 5 g of sodium chloride, 0.5 g of potassium chloride, 0.2 g of boric acid, 0.01 g of borax, 3-5 g of glycerol (1% w / v), 0.01-0.05 g of benzalkonium chloride (0.01% w / v), and water for injection is added to 400 ml.

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