Levofloxacin eye drops and preparation method thereof

Abstract

The invention belongs to the technical field of levofloxacin eye drops, and particularly relates to levofloxacin eye drops and a preparation method thereof. According to 100 mL of the levofloxacin eye drops, the levofloxacin eye drops comprise 0.35-0.50 g of levofloxacin, 0.03-0.06 g of sodium hyaluronate, 1.0-3.0 g of citric acid, 2.0 g of potassium citrate, 0.003-0.010 g of domiphen and 0.8-2.0 g of glycerin, the pH is adjusted to 6.5 + / -0.2 with sodium hydroxide, and the total volume is 100 mL with water for injection. The preparation method comprises the following steps: dissolving a buffer system, adding the main drug, swelling sodium hyaluronate, adding the auxiliary material to adjust the pH value, filtering and sterilizing. Sodium hyaluronate prolongs the retention time of the medicine on the ocular surface, a citric acid-potassium citrate buffer system improves the stability, domiphen reduces irritation, and glycerol adjusts osmotic pressure and resists oxidation. The eye drops provided by the invention have excellent stability, high biocompatibility and extremely low irritation, and are particularly suitable for patients needing long-term medication and contact lens wearing people. The preparation process is simple, convenient and feasible, does not need special equipment, and is lower in production cost.

Description

Technical Field

[0001] The invention belongs to the technical field of levofloxacin eye drop preparations, and particularly relates to levofloxacin eye drops and a preparation method thereof. Background Art

[0002] Levofloxacin is a broad-spectrum quinolone antibacterial drug with excellent antimicrobial activity and tissue penetration. It is widely used to treat eye infections caused by sensitive bacteria, such as conjunctivitis, keratitis, and blepharitis. Due to its good water solubility, broad antimicrobial spectrum, and clear mechanism of action, it has been widely used in the development of topical ophthalmic preparations in recent years.

[0003] As a common ophthalmic dosage form, eye drops are required to have good biocompatibility, appropriate viscosity and osmotic pressure, and at the same time, the chemical stability of the main drug during storage and the physical stability during use should be guaranteed. However, quinolones are prone to oxidative degradation or photolysis reactions under light, high temperature or unstable pH conditions, resulting in reduced efficacy and even the production of harmful impurities, affecting the safety and effectiveness of the drug. In addition, eye drops have a short residence time in the eye, and the dynamic renewal mechanism of tears will quickly clear the drug that has been dropped into the ocular surface. Frequent medication is required, which brings inconvenience to patients and increases the difficulty of compliance.

[0004] To prolong drug retention on the ocular surface and improve bioavailability, some studies have attempted to introduce adhesive excipients, such as hydropropyl methylcellulose (HPMC) and polyvinyl alcohol (PVA), to increase solution viscosity. However, while these materials enhance adhesion, they can also cause some irritation to the ocular surface, making them less comfortable, especially for long-term users or those who wear contact lenses. Furthermore, while some commonly used antibacterial agents, such as benzalkonium chloride (BAC), have strong antibacterial effects, they have been shown to be potentially toxic to corneal epithelial cells and may induce dry eye or inflammatory reactions.

[0005] In terms of buffer system selection, common phosphate and borate buffers, while providing a relatively stable pH environment, also affect the chemical stability of the formulation to a certain extent. Furthermore, electrolytes such as sodium chloride are often added to regulate osmotic pressure, but the presence of chloride ions accelerates the oxidation reaction of levofloxacin, which is detrimental to the long-term storage of the formulation.

[0006] Therefore, how to ensure the stability, safety, comfort and prolong the retention time on the ocular surface of the preparation while ensuring the antibacterial effect is a technical problem that needs to be solved urgently in the current research and development of levofloxacin eye drops. Summary of the Invention

[0007] In response to the shortcomings of the existing technology, the present invention provides a levofloxacin eye drop and a preparation method thereof. The present invention aims to develop a levofloxacin eye drop with good stability, high biocompatibility, low irritation, and suitable for contact lens wearers and long-term medication patients, as well as a simple and feasible preparation method thereof, to meet the actual needs of clinical patients, especially those who take long-term medication.

[0008] The first aspect of the present invention is to provide a levofloxacin eye drop, each 100 mL of which contains the following components:

[0009] Levofloxacin 0.35 g–0.50 g;

[0010] Sodium hyaluronate 0.03g–0.06g;

[0011] Citric acid 1.0g–3.0g;

[0012] Potassium citrate 1.0g–3.0g;

[0013] Domiphene 0.003g–0.010g;

[0014] Glycerol 0.8g–2.0g;

[0015] pH adjusters

[0016] The balance is water for injection.

[0017] As a further optimization solution for levofloxacin eye drops, the pH value of the system was adjusted to 6.5±0.2 by a pH regulator.

[0018] As a further optimization scheme for levofloxacin eye drops, the pH regulator is sodium hydroxide.

[0019] As a further optimization scheme of levofloxacin eye drops, the levofloxacin content is 0.40g–0.50g, the sodium hyaluronate content is 0.04g–0.06g, and the total amount of citric acid and potassium citrate is 3.0g–5.0g.

[0020] The second aspect of the present invention is to provide a method for preparing levofloxacin eye drops, which comprises the following preparation steps according to the formula of the above-mentioned levofloxacin eye drops:

[0021] (a) taking a portion of water for injection, adding citric acid and potassium citrate in sequence, stirring and dissolving to form a buffer system;

[0022] (b) adding levofloxacin and stirring until completely dissolved;

[0023] (c) slowly adding sodium hyaluronate while stirring until fully swollen;

[0024] (d) adding domiphene and glycerol and stirring evenly;

[0025] (e) adjusting the pH of the system to 6.5 ± 0.2 using a pH regulator;

[0026] (f) Add water for injection to 100 mL and filter sterilize;

[0027] (g) filling and sterilizing to obtain the finished eye drops.

[0028] As a further optimized solution for the preparation of levofloxacin eye drops, the amount of water for injection used in step (a) is 70%-85% of the total volume.

[0029] As a further optimization scheme for the preparation method of levofloxacin eye drops, the addition rate of sodium hyaluronate in step (c) is 0.5-1.0 g / min, and the stirring rate is 200-400 rpm.

[0030] As a further optimization scheme for the preparation method of levofloxacin eye drops, the pH value in step (e) is controlled to 6.5±0.1.

[0031] As a further optimization scheme for the preparation method of levofloxacin eye drops, two-stage filtration is adopted in step (f), first pre-filtration through a 0.8 μm filter membrane, and then sterilization through a 0.22 μm microporous filter membrane.

[0032] As a further optimization scheme for the preparation method of levofloxacin eye drops, the sterilization in step (g) is carried out by hot pressing sterilization at 121° C. for 15–20 minutes.

[0033] Beneficial effects

[0034] The present invention significantly improves the comprehensive performance of levofloxacin eye drops by optimizing the formula composition and preparation process. Sodium hyaluronate is used to construct a bioadhesive thickening system, which effectively prolongs the drug's retention time on the ocular surface and enhances the therapeutic effect. The citric acid-potassium citrate buffer system is combined to accurately control the pH value, forming a stable chemical environment, inhibiting the drug's oxidative degradation and photolysis reaction, thereby significantly improving the physicochemical stability of the preparation. The low-irritation antibacterial agent domiphene significantly reduces irritation to the ocular surface tissue while ensuring antibacterial efficacy. The osmotic pressure regulation and antioxidant function of glycerol are combined to further enhance the safety of the preparation and comfort of use. The prepared eye drops are particularly suitable for patients who require long-term medication and people who wear contact lenses, and have multiple advantages such as long-term sustained release, high safety, and good biocompatibility. DETAILED DESCRIPTION

[0035] 1. Formula composition (based on 100mL)

[0036] Levofloxacin eye drops include the following components: levofloxacin 0.35g–0.50g; sodium hyaluronate 0.03g–0.06g; citric acid 1.0g–3.0g; potassium citrate 2.0g; domiphene 0.003g–0.010g; glycerol 0.8g–2.0g; sodium hydroxide (appropriate amount, used to adjust the pH to within the range of 6.5+±0.2); water for injection is added to 100mL.

[0037] 2. Preparation Method

[0038] Place a portion of the water for injection in a clean container, add citric acid and potassium citrate in sequence, and stir to completely dissolve to form a pH buffer system. Add levofloxacin and continue stirring until dissolved. Then, slowly add sodium hyaluronate to the container, stirring while adding, so that it fully swells to form a thickening system. Add domiphene and glycerol and stir evenly. Then use sodium hydroxide solution to adjust the system pH to approximately 6.5. Add water for injection to 100 mL in the container, stir evenly, and filter through a 0.22μm microporous membrane to remove possible impurities and microorganisms. Fill the filtrate into a sterile eye drop bottle and sterilize by autoclaving to produce levofloxacin eye drops. The entire preparation process must be carried out in a clean environment that meets GMP standards.

[0039] The present invention is further illustrated below by means of specific examples. These examples are exemplary and are intended to illustrate the problem and explain the present invention, but are not intended to be limiting.

[0040] Example 1

[0041] 1. Formula composition (based on 100mL)

[0042] Levofloxacin 0.488g

[0043] Sodium hyaluronate 0.04g

[0044] Citric acid 2.0g

[0045] Potassium citrate 2.0g

[0046] Domiphene 0.005g

[0047] Glycerol 1.2g

[0048] Sodium hydroxide (as needed to adjust pH)

[0049] Add water for injection to 100mL

[0050] 2. Preparation Method

[0051] First, place an appropriate amount of water for injection (approximately 80 mL) in a clean container. Add citric acid and potassium citrate in sequence, stirring until completely dissolved to form a pH buffer system. Next, add levofloxacin and continue stirring until dissolved, stirring slowly during the process to avoid excessive bubbles. Then, slowly add sodium hyaluronate to the container, stirring while adding, so that it fully swells to form a thickening system. After that, add domiphene and glycerol and stir evenly. Then, use sodium hydroxide solution to adjust the pH of the system to approximately 6.5. During the adjustment process, continuously monitor the pH value until it stabilizes at the preset value. Finally, add water for injection to 100 mL of the container, stir evenly, filter through a 0.22 μm microporous membrane to remove possible impurities and microorganisms, and fill the filtrate into a sterile eye drop bottle. Autoclave sterilize at 121°C for 15 minutes to produce levofloxacin eye drops. The entire preparation process is carried out in a clean environment that meets GMP standards.

[0052] Example 2

[0053] 1. Formula composition (based on 100mL)

[0054] Levofloxacin 0.35g

[0055] Sodium hyaluronate 0.03g

[0056] 1.5g citric acid

[0057] Potassium citrate 1.5g

[0058] Domiphene 0.003g

[0059] Glycerol 0.8g

[0060] Sodium hydroxide (as needed to adjust pH)

[0061] Add water for injection to 100mL

[0062] 2. Preparation Method

[0063] First, take an appropriate amount of water for injection (approximately 80 mL) and place it in a clean container. Add citric acid and potassium citrate in sequence and stir until completely dissolved to form a pH buffer system. Next, add levofloxacin and continue stirring until dissolved. Stir slowly during this period to avoid excessive bubbles. Then, slowly add sodium hyaluronate to the container, stirring while adding, so that it fully swells to form a thickening system. After that, add domiphene and glycerol and stir evenly. Then use sodium hydroxide solution to adjust the pH of the system to approximately 6.5. During the adjustment process, continuously monitor the pH value until it stabilizes at the preset value. Finally, add water for injection to 100 mL of the container, stir evenly, filter through a 0.22 μm microporous membrane to remove possible impurities and microorganisms, and fill the filtrate into a sterile eye drop bottle. Autoclave sterilize at 121°C for 20 minutes to prepare levofloxacin eye drops. The entire preparation process is carried out in a clean environment that meets GMP standards.

[0064] Example 3

[0065] 1. Formula composition (based on 100mL)

[0066] Levofloxacin 0.45g

[0067] Sodium hyaluronate 0.06g

[0068] 2.5g citric acid

[0069] Potassium citrate 2.5g

[0070] Domifene 0.008g

[0071] 1.5g glycerin

[0072] Sodium hydroxide (as needed to adjust pH)

[0073] Add water for injection to 100mL

[0074] 2. Preparation Method

[0075] First, place an appropriate amount of water for injection (approximately 80 mL) in a clean container. Add citric acid and potassium citrate sequentially, stirring until completely dissolved to form a pH buffer system. Next, add levofloxacin and continue stirring until dissolved, stirring slowly to avoid excessive bubbles. Then, slowly add sodium hyaluronate to the container, stirring while adding, until it fully swells to form a thickening system. After that, add domiphene and glycerol and stir evenly. Then, adjust the pH of the system to approximately 6.5 with sodium hydroxide solution. During the adjustment process, continuously monitor the pH value until it stabilizes at the preset value. Finally, add water for injection to 100 mL of the container, stir evenly, pre-filter through a 0.8 μm filter membrane, and then filter through a 0.22 μm microporous filter membrane to remove possible impurities and microorganisms. The filtrate is filled into sterile eye drop bottles and sterilized by autoclaving at 121°C for 15 minutes to produce levofloxacin eye drops. The entire preparation process is carried out in a clean environment that meets GMP standards.

[0076] Example 4

[0077] 1. Formula composition (based on 100mL)

[0078] Levofloxacin 0.40g

[0079] Sodium hyaluronate 0.04g

[0080] Citric acid 1.0g

[0081] Potassium citrate 3.0g

[0082] Domiphene 0.005g

[0083] Glycerol 1.0g

[0084] Sodium hydroxide (as needed to adjust pH)

[0085] Add water for injection to 100mL

[0086] 2. Preparation Method

[0087] First, take an appropriate amount of water for injection (approximately 80 mL) and place it in a clean container. Add citric acid and potassium citrate in sequence and stir until completely dissolved to form a pH buffer system. Next, add levofloxacin and continue stirring until dissolved. Stir slowly during this period to avoid excessive bubbles. Then, slowly add sodium hyaluronate to the container, stirring while adding, so that it fully swells to form a thickening system. After that, add domiphene and glycerol and stir evenly. Then use sodium hydroxide solution to adjust the pH of the system to approximately 6.5. During the adjustment process, continuously monitor the pH value until it stabilizes at the preset value. Finally, add water for injection to 100 mL of the container, stir evenly, filter through a 0.22 μm microporous membrane to remove possible impurities and microorganisms, and fill the filtrate into a sterile eye drop bottle. Autoclave sterilize at 121°C for 20 minutes to prepare levofloxacin eye drops. The entire preparation process is carried out in a clean environment that meets GMP standards.

[0088] Example 5

[0089] 1. Formula composition (based on 100mL)

[0090] Levofloxacin 0.50g

[0091] Sodium hyaluronate 0.03g

[0092] Citric acid 3.0g

[0093] Potassium citrate 1.0g

[0094] Domiphene 0.010g

[0095] Glycerol 2.0g

[0096] Sodium hydroxide (as needed to adjust pH)

[0097] Add water for injection to 100mL

[0098] 2. Preparation Method

[0099] First, place an appropriate amount of water for injection (approximately 80 mL) in a clean container. Add citric acid and potassium citrate in sequence, stirring until completely dissolved to form a pH buffer system. Next, add levofloxacin and continue stirring until dissolved, stirring slowly during the process to avoid excessive bubbles. Then, slowly add sodium hyaluronate to the container, stirring while adding, so that it fully swells to form a thickening system. After that, add domiphene and glycerol and stir evenly. Then, use sodium hydroxide solution to adjust the pH of the system to approximately 6.5. During the adjustment process, continuously monitor the pH value until it stabilizes at the preset value. Finally, add water for injection to 100 mL of the container, stir evenly, filter through a 0.22 μm microporous membrane to remove possible impurities and microorganisms, and fill the filtrate into a sterile eye drop bottle. Autoclave sterilize at 121°C for 15 minutes to produce levofloxacin eye drops. The entire preparation process is carried out in a clean environment that meets GMP standards.

[0100] Comparative Example 1

[0101] Based on Example 1, the content of sodium hyaluronate was adjusted to 0 g, and the other components and preparation process remained unchanged.

[0102] Comparative Example 2

[0103] On the basis of Example 1, citric acid and potassium citrate were adjusted to 1.5 g of sodium dihydrogen phosphate and 2.2 g of dipotassium hydrogen phosphate, and other components and preparation process remained unchanged.

[0104] Comparative Example 3

[0105] On the basis of Example 1, the amount of domiphene was adjusted to 0.01 g of benzalkonium chloride, and the other components and preparation process remained unchanged.

[0106] Comparative Example 4

[0107] On the basis of Example 1, the amount of glycerol was adjusted to 0.9 g of sodium chloride, and the other components and preparation process remained unchanged.

[0108] Comparative Example 5

[0109] On the basis of Example 1, the sodium hyaluronate was adjusted to 0 g, the glycerol was adjusted to 0.9 g of sodium chloride, and the other components and preparation process remained unchanged.

[0110] Test Case

[0111] The stability test used high-performance liquid chromatography (HPLC) to determine the content of levofloxacin and related substances. The specific procedures were based on the general rules of Part IV of the 2020 edition of the Chinese Pharmacopoeia 0512. The preparation was placed under conditions of 40°C and 75% relative humidity for an accelerated test for three months. During this period, samples were taken regularly and the changes in levofloxacin content and the production of related substances were measured by HPLC. Visual colorimetry was used to compare the color changes of the preparation with the pharmacopoeial colorimetric solution to examine the stability of the preparation under high temperature and humidity conditions.

[0112] The ocular surface retention test uses the rabbit eye sodium fluorescein labeling method to measure the ocular surface retention of eye drops. Fluorescein sodium-labeled eye drops are instilled into the rabbit conjunctival sac, and the clearance rate of fluorescein sodium in the tear fluid is dynamically monitored to calculate the drug's ocular surface retention half-life. This method simulates the physiological environment of the human eye to assess the ability of a formulation to remain on the ocular surface, reflecting the effects of drug adhesion to ocular surface tissues and tear clearance rate on drug retention.

[0113] The safety assessment refers to the Draize rabbit eye irritation test standard. The preparation is dripped into the conjunctival sac of the rabbit eye. The degree of damage to the cornea, conjunctiva and iris is observed 1 hour, 24 hours, 48 hours and 72 hours after the instillation, including whether there is turbidity, congestion, edema and other phenomena. The irritation reaction is quantitatively scored according to the standard scoring system to evaluate the irritation and safety of the preparation to the ocular surface tissue. Scoring standard: Corneal damage is scored on a scale of 0-4 points, 0 for no turbidity, 1 for scattered or diffuse turbidity and the iris is clearly visible, 2 for easy identification of translucent areas but blurred iris, 3 for gray-white translucent areas, unclear iris details and barely visible pupil size, 4 for opaque cornea and unrecognizable iris; iris damage is scored on a scale of 0-2 points, 0 for normal, 1 for deepened wrinkles, congestion, swelling, mild congestion around the cornea and pupil reaction to light, 2 for bleeding, visible damage to the iris Dead or unresponsive to light; conjunctival injury is scored on a scale of 0-10, with 0 for normal blood vessels, 1 for bright red congestion, 2 for dark red congestion with difficult-to-distinguish blood vessels, and 3 for diffuse purple-red congestion; edema is scored as 0 for no edema, 1 for mild edema, 2 for obvious edema with ectropion, 3 for edema to the point of nearly half closure of the eyelid, and 4 for edema exceeding half closure; secretion is scored as 0 for none, 1 for a small amount, 2 for moistening the eyelids and eyelashes, and 3 for moistening the entire eye area.

[0114] The viscosity was measured using a rotational viscometer at 20°C. The operating procedures were in accordance with Method 2, Part 0633 of the 2020 edition of the Chinese Pharmacopoeia.

[0115] The results of Examples 1-5 are shown in Table 1, and the results of Comparative Examples 1-5 are shown in Table 2.

[0116] Table 1

[0117]

[0118] Table 2

[0119]

[0120] The stability test results show that after 3 months of accelerated testing at 40°C, the content retention rates of Examples 1-5 were all between 97.0% and 98.5%, the increase in related substances was controlled at 0.08% to 0.20%, and the color did not change, showing good stability. In the comparative examples, comparative example 2 replaced the buffer pair with sodium dihydrogen phosphate and dipotassium hydrogen phosphate, comparative example 4 replaced glycerol with sodium chloride, and comparative example 5 simultaneously removed sodium hyaluronate and replaced glycerol with sodium chloride. The content retention rates dropped to 89%, 92%, and 85%, respectively, and the related substances increased significantly, and the color turned yellow, and the stability decreased significantly. Comparative example 1 removed sodium hyaluronate, and comparative example 3 replaced domiphene with benzalkonium chloride. The stability was relatively good, but still not as good as the examples.

[0121] Ocular surface retention time testing results showed that Examples 1-5 had ocular surface retention half-lives ranging from 27.2 to 28.9 minutes, significantly extending drug retention time on the ocular surface. In contrast, Comparative Example 1, which removed sodium hyaluronate, and Comparative Example 5, which removed sodium hyaluronate and replaced glycerol with sodium chloride, shortened their ocular surface retention half-lives to 8.7 and 7.3 minutes, respectively. While the retention half-lives of Comparative Examples 2, 3, and 4 were similar to those of the Examples, they were still slightly lower overall.

[0122] Safety assessment results showed that Examples 1-5 all had low rabbit eye irritation scores, ranging from 0.4 to 0.7, indicating that the formulations were less irritating to the eye. Comparative Example 3, in which domiphene was replaced with benzalkonium chloride, achieved a rabbit eye irritation score of 3.2, significantly higher than that of the Examples. Comparative Example 5, in which sodium hyaluronate was removed and glycerol was replaced with sodium chloride, achieved a rabbit eye irritation score of 2.1, also significantly higher than that of the Examples.

[0123] The results of viscosity measurement show that the kinematic viscosity of Examples 1-5 is 5.5-6.0 mm 2 / s, which is in the appropriate thickening range. Comparative Examples 1 and 5 have a viscosity that is significantly reduced to 1.5 mm due to the removal of sodium hyaluronate. 2 / s and 1.6mm 2 / s; the viscosities of comparative examples 2, 3, and 4 are similar to those of the embodiment.

[0124] In summary, it can be seen from Comparative Examples 1 and 5 that after removing sodium hyaluronate, the ocular surface retention half-life is significantly shortened and the viscosity is greatly reduced, indicating that sodium hyaluronate plays a key role in extending the drug ocular surface retention time by increasing solution viscosity and bioadhesion. After Comparative Example 2 replaced the buffer system, stability was significantly reduced, indicating that the citric acid-potassium citrate buffer can effectively maintain pH stability, inhibit the oxidative degradation and photolysis reaction of levofloxacin, and ensure drug stability. After Comparative Example 3 replaced domiphene with benzalkonium chloride, the rabbit eye irritation score was significantly increased, proving that domiphene, as an antibacterial agent, is less irritating than benzalkonium chloride, has better safety, and cooperates with levofloxacin to inhibit bacteriostasis. After Comparative Example 4 replaced glycerol with sodium chloride, stability was reduced, indicating that glycerol, as an osmotic pressure regulator, can avoid chloride ions accelerating drug oxidation, while enhancing solution moisture retention, improving stability and eye comfort.

[0125] Further comparative analysis of the embodiments and comparative examples shows that the present invention's formulation effectively solves the problems of poor stability and short pot life of traditional levofloxacin eye drops through the coordination of sodium hyaluronate thickening, citric acid buffering, domiphene antibacterial, and glycerol osmotic adjustment. Simultaneously, the formulation has the characteristics of low irritation and antibacterial, high safety, and is suitable for long-term medication patients and contact lens wearers. In terms of preparation technology, sterility can be ensured by conventional hot pressure sterilization, without the need for special equipment, reducing production costs, and having good practicality and application prospects.

[0126] The above embodiments are exemplary and intended to illustrate the technical concepts and features of the present invention so that those skilled in the art can understand the present invention and implement it accordingly. They are not intended to limit the scope of protection of the present invention. Any equivalent changes or modifications made in accordance with the spirit of the present invention are intended to be included within the scope of protection of the present invention.

Claims

1. A levofloxacin eye drop, characterized in that: Each 100mL contains the following components: Levofloxacin 0.35 g–0.50 g; Sodium hyaluronate 0.03g–0.06g; Citric acid 1.0g–3.0g; Potassium citrate 1.0g–3.0g; Domiphene 0.003g–0.010g; Glycerol 0.8g–2.0g; pH adjusters The balance is water for injection.

2. Levofloxacin eye drops according to claim 1, characterized in that: The pH adjuster adjusts the pH value of the system to 6.5±0.

2.

3. Levofloxacin eye drops according to claim 1, characterized in that: The pH regulator is sodium hydroxide.

4. The levofloxacin eye drops according to any one of claims 1 to 3, characterized in that: The levofloxacin content is 0.40g-0.50g, the sodium hyaluronate content is 0.04g-0.06g, and the total amount of citric acid and potassium citrate is 3.0g-5.0g.

5. A method for preparing levofloxacin eye drops, characterized in that: The formula of levofloxacin eye drops according to any one of claims 1 to 4, comprising the following preparation steps: (a) taking a portion of water for injection, adding citric acid and potassium citrate in sequence, stirring and dissolving to form a buffer system; (b) adding levofloxacin and stirring until completely dissolved; (c) slowly adding sodium hyaluronate while stirring until fully swollen; (d) adding domiphene and glycerol and stirring evenly; (e) adjusting the pH of the system to 6.5 ± 0.2 using a pH regulator; (f) Add water for injection to 100 mL and filter sterilize; (g) filling and sterilizing to obtain the finished eye drops.

6. The method for preparing levofloxacin eye drops according to claim 5, wherein: The amount of water for injection in step (a) is 70%–85% of the total volume.

7. The method for preparing levofloxacin eye drops according to claim 5, wherein: In step (c), the sodium hyaluronate is added at a rate of 0.5-1.0 g / min, and the stirring rate is 200-400 rpm.

8. The method for preparing levofloxacin eye drops according to claim 5, wherein: In step (e), the pH value is controlled to 6.5±0.

1.

9. The method for preparing levofloxacin eye drops according to claim 5, wherein: In step (f), two-stage filtration is adopted, first pre-filtration through a 0.8 μm filter membrane, and then sterilization through a 0.22 μm microporous filter membrane.

10. The method for preparing levofloxacin eye drops according to claim 5, wherein: In step (g), sterilization is performed by hot pressing at 121° C. for 15–20 minutes.

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