An eye drop of tobramycin

Abstract

This invention relates to a tobramycin eye drop. Specifically, this invention provides a tobramycin eye drop comprising tobramycin, polyethylene glycol 400, glycerin, sorbitol, alanine, hydroxypropyl cellulose, sodium dihydrogen phosphate, disodium hydrogen phosphate, and water. The tobramycin eye drop of this invention has the advantage of low ocular irritation, significantly improving ocular drug administration compliance. Furthermore, the tobramycin eye drop of this invention exhibits excellent light and high-temperature stability, ensuring the quality and safety of the tobramycin eye drop, thereby enhancing its application value.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical preparations, and more specifically to a tobramycin eye drop. Background Technology

[0002] Tobramycin (CAS No.: 32986-56-4) is an aminoglycoside antibiotic used clinically to treat a variety of bacterial infections, especially those caused by Gram-negative bacteria. The structural formula of tobramycin is as follows:

[0003]

[0004] Tobramycin eye drops are a commonly used clinical preparation of tobramycin. Clinically, tobramycin eye drops are mainly used to treat local infections of the external eye and adnexa caused by susceptible bacterial strains, such as conjunctivitis, keratitis, and blepharitis. Tobramycin eye drops are administered via eye drops, offering advantages such as convenient administration and rapid therapeutic effect on ocular bacterial infections, leading to their widespread clinical use. However, existing tobramycin eye drops suffer from strong ocular irritation, resulting in poor patient compliance. Furthermore, they exhibit poor stability under light and high temperatures, easily precipitating under these conditions. This leads to quality and safety issues during storage and transportation, increasing storage and transportation costs and thus reducing the practical value of tobramycin eye drops.

[0005] Therefore, there is a need in the field to develop a tobramycin eye drop that improves ocular drug administration compliance and stability, thereby enhancing the application value of tobramycin eye drops. Summary of the Invention

[0006] The purpose of this invention is to provide a tobramycin eye drop that improves ocular drug administration compliance and stability.

[0007] The first aspect of the present invention provides a tobramycin eye drop, the tobramycin eye drop comprising tobramycin, polyethylene glycol 400, glycerin, sorbitol, alanine, hydroxypropyl cellulose, sodium dihydrogen phosphate, disodium hydrogen phosphate and water.

[0008] Preferably, the tobramycin is 1-5 parts by weight, more preferably 2-4 parts by weight, even more preferably 2.8-3.2 parts by weight, and most preferably 3.0 parts by weight.

[0009] Preferably, the tobramycin content is 1-5 mg / ml, more preferably 2-4 mg / ml, even more preferably 2.8-3.2 mg / ml, and most preferably 3.0 mg / ml.

[0010] Preferably, the polyethylene glycol 400 is 1-3 parts by weight, more preferably 1.5-2.5 parts by weight, even more preferably 1.8-2.2 parts by weight, and most preferably 2.0 parts by weight.

[0011] Preferably, the content of polyethylene glycol 400 is 1-3 mg / ml, more preferably 1.5-2.5 mg / ml, even more preferably 1.8-2.2 mg / ml, and most preferably 2.0 mg / ml.

[0012] Preferably, the glycerol is 0.5-3.0 parts by weight, more preferably 1.0-2.0 parts by weight, even more preferably 1.3-1.7 parts by weight, and most preferably 1.5 parts by weight.

[0013] Preferably, the glycerol content is 0.5-3.0 mg / ml, more preferably 1.0-2.0 mg / ml, even more preferably 1.3-1.7 mg / ml, and most preferably 1.5 mg / ml.

[0014] Preferably, the sorbitol is 0.2-2.0 parts by weight, more preferably 0.5-1.5 parts by weight, even more preferably 0.8-1.2 parts by weight, and most preferably 1.0 parts by weight.

[0015] Preferably, the sorbitol content is 0.2-2.0 mg / ml, more preferably 0.5-1.5 mg / ml, even more preferably 0.8-1.2 mg / ml, and most preferably 1.0 mg / ml.

[0016] Preferably, the alanine content is 0.5-2.0 parts by weight, more preferably 0.8-1.6 parts by weight, even more preferably 1.0-1.4 parts by weight, and most preferably 1.2 parts by weight.

[0017] Preferably, the alanine content is 0.5-2.0 mg / ml, more preferably 0.8-1.6 mg / ml, even more preferably 1.0-1.4 mg / ml, and most preferably 1.2 mg / ml.

[0018] Preferably, the hydroxypropyl cellulose is 0.5-2.0 parts by weight, more preferably 0.5-1.5 parts by weight, even more preferably 0.6-1.0 parts by weight, and most preferably 0.8 parts by weight.

[0019] Preferably, the hydroxypropyl cellulose content is 0.5-2.0 mg / ml, more preferably 0.5-1.5 mg / ml, even more preferably 0.6-1.0 mg / ml, and most preferably 0.8 mg / ml.

[0020] Preferably, the sodium dihydrogen phosphate is 1-3 parts by weight, more preferably 1.5-2.5 parts by weight, even more preferably 1.8-2.2 parts by weight, and most preferably 2.0 parts by weight.

[0021] Preferably, the sodium dihydrogen phosphate content is 1-3 mg / ml, more preferably 1.5-2.5 mg / ml, even more preferably 1.8-2.2 mg / ml, and most preferably 2.0 mg / ml.

[0022] Preferably, the disodium hydrogen phosphate is 5-7 parts by weight, more preferably 5.5-6.5 parts by weight, even more preferably 5.8-6.2 parts by weight, and most preferably 6.0 parts by weight.

[0023] Preferably, the content of disodium hydrogen phosphate is 5-7 mg / ml, more preferably 5.5-6.5 mg / ml, even more preferably 5.8-6.2 mg / ml, and most preferably 6.0 mg / ml.

[0024] Preferably, the water is 900-1100 parts by weight, more preferably 950-1050 parts by weight, even more preferably 980-1020 parts by weight, and most preferably 1000 parts by weight.

[0025] Preferably, the water includes water for injection.

[0026] Preferably, the tobramycin eye drops comprise:

[0027] Components Dosage Tobramycin 2-4 parts by weight Polyethylene glycol 400 1-3 parts by weight glycerin 0.5-3.0 parts by weight Sorbitol 0.2-3 parts by weight alanine 0.5-2.0 parts by weight Hydroxypropyl cellulose 0.5-2.0 parts by weight Sodium dihydrogen phosphate 1-3 parts by weight disodium hydrogen phosphate 5-7 parts by weight; and water 900-1100 parts by weight.

[0028] Preferably, the tobramycin eye drops comprise:

[0029]

[0030]

[0031] Preferably, the tobramycin eye drops comprise:

[0032] Components Dosage Tobramycin 2.8-3.2 parts by weight Polyethylene glycol 400 1.8-2.2 parts by weight glycerin 1.3-1.7 parts by weight Sorbitol 0.8-1.2 parts by weight alanine 1.0-1.4 parts by weight Hydroxypropyl cellulose 0.6-1.0 parts by weight Sodium dihydrogen phosphate 1.8-2.2 parts by weight disodium hydrogen phosphate 5.8-6.2 parts by weight; and water 980-1020 parts by weight.

[0033] Preferably, the tobramycin eye drops comprise:

[0034] Components Dosage Tobramycin 3.0 parts by weight Polyethylene glycol 400 2.0 parts by weight glycerin 1.5 parts by weight Sorbitol 1.0 part by weight alanine 1.2 parts by weight Hydroxypropyl cellulose 0.8 parts by weight Sodium dihydrogen phosphate 2.0 parts by weight disodium hydrogen phosphate 6.0 parts by weight; and water 1000 parts by weight.

[0035] Preferably, the tobramycin eye drops comprise:

[0036] Components Dosage Tobramycin 3.0g Polyethylene glycol 400 2.0g glycerin 1.5g Sorbitol 1.0g alanine 1.2g Hydroxypropyl cellulose 0.8g Sodium dihydrogen phosphate 2.0g disodium hydrogen phosphate 6.0g Add water until 1000ml。

[0037] A second aspect of the present invention provides a method for preparing tobramycin eye drops as described in the first aspect of the present invention, the method comprising the steps of:

[0038] The tobramycin eye drops were obtained by mixing tobramycin, polyethylene glycol 400, glycerin, sorbitol, alanine, hydroxypropyl cellulose, sodium dihydrogen phosphate, disodium hydrogen phosphate, and water.

[0039] Preferably, the method includes the following steps:

[0040] Add 75-85% of the prescribed amount of water to a mixing tank. Under conditions of 35-45℃, add the prescribed amounts of polyethylene glycol 400, glycerin, sodium dihydrogen phosphate, and disodium hydrogen phosphate. After stirring and dissolving, add the prescribed amount of hydroxypropyl cellulose and stir and dissolve. Then add the prescribed amount of tobramycin and stir and dissolve to obtain a drug solution. Add the prescribed amounts of sorbitol and alanine to the drug solution and stir and dissolve. Add water to the drug solution to the volume required for preparation, filter, and obtain tobramycin eye drops.

[0041] Preferably, the filtration includes sequential filtration through 0.45μm and 0.22μm microporous membranes.

[0042] Preferably, the method includes the following steps:

[0043] Add 80% of the prescribed amount of water to the mixing tank. At 40°C, add the prescribed amounts of polyethylene glycol 400, glycerin, sodium dihydrogen phosphate, and disodium hydrogen phosphate. After stirring and dissolving, add the prescribed amount of hydroxypropyl cellulose and stir and dissolve. Then add the prescribed amount of tobramycin and stir and dissolve to obtain the drug solution. Add the prescribed amounts of sorbitol and alanine to the drug solution and stir and dissolve. Add water to the mixing volume, filter, and obtain tobramycin eye drops.

[0044] In a third aspect, the present invention provides a medicine box comprising tobramycin eye drops as described in the first aspect of the present invention.

[0045] Preferably, the medicine box also includes a transparent container.

[0046] Preferably, the tobramycin eye drops are dispensed into the transparent container.

[0047] Preferably, the transparent container includes a transparent PET bottle.

[0048] The fourth aspect of the present invention provides the use of tobramycin eye drops as described in the first aspect of the present invention in the preparation of a medicament for treating local infections of the external eye and its appendages caused by bacteria.

[0049] It should be understood that, within the scope of this invention, the above-described technical features of this invention and the technical features specifically described below (such as in the embodiments) can be combined with each other to form new or preferred technical solutions. Detailed Implementation

[0050] This invention provides a tobramycin eye drop solution comprising tobramycin, polyethylene glycol 400, glycerin, sorbitol, alanine, hydroxypropyl cellulose, sodium dihydrogen phosphate, disodium hydrogen phosphate, and water. The tobramycin eye drop solution with this specific composition exhibits the advantage of low ocular irritation, significantly improving ocular drug administration compliance. Furthermore, the tobramycin eye drop solution of this invention demonstrates excellent light and high-temperature stability, thereby significantly enhancing the application value of tobramycin eye drops.

[0051] the term

[0052] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0053] As used herein, the terms “comprising,” “including,” and “containing” are used interchangeably and include not only closed definitions but also semi-closed and open definitions. In other words, the terms include “consisting of” and “substantially consisting of”.

[0054] As used in this article, the term "PET" refers to polyethylene terephthalate, also known as polyethylene terephthalate.

[0055] As used in this article, the term "polyethylene glycol 400" is translated into English as Poly(ethylene glycol) 400, or simply PEG-400.

[0056] As used in this article, the English term for "hydroxypropyl cellulose" is Hydroxypropyl Cellulose.

[0057] As used herein, the term "parts by weight" can be any fixed weight expressed in milligrams, grams, or kilograms (e.g., 1 mg, 1 g, or 1 kg, etc.). For example, a composition consisting of 1 part by weight of component a and 9 parts by weight of component b can be a composition consisting of 1 gram of component a + 9 grams of component b, or 10 grams of component a + 90 grams of component b, etc. In the tobramycin eye drops described herein, the percentage content of a component = (the number of parts by weight of that component / the sum of the number of parts by weight of all components) × 100%. For example, in a composition consisting of 1 part by weight of component a and 9 parts by weight of component b, the content of component a is 10%, and the content of component b is 90%.

[0058] Tobramycin eye drops and its preparation method

[0059] This invention provides a tobramycin eye drop with low ocular irritation and high stability, thereby improving the application value of tobramycin eye drops.

[0060] The tobramycin eye drops of the present invention may include (but are not limited to) tobramycin, polyethylene glycol 400, glycerin, sorbitol, alanine, hydroxypropyl cellulose, sodium dihydrogen phosphate, disodium hydrogen phosphate and water.

[0061] In a preferred embodiment of the present invention, the tobramycin may be 1-5 parts by weight, more preferably 2-4 parts by weight, more preferably 2.8-3.2 parts by weight, and most preferably 3.0 parts by weight.

[0062] In a preferred embodiment of the present invention, the polyethylene glycol 400 may be 1-3 parts by weight, more preferably 1.5-2.5 parts by weight, more preferably 1.8-2.2 parts by weight, and most preferably 2.0 parts by weight.

[0063] In a preferred embodiment of the present invention, the glycerol may be 0.5-3.0 parts by weight, more preferably 1.0-2.0 parts by weight, more preferably 1.3-1.7 parts by weight, and most preferably 1.5 parts by weight.

[0064] In a preferred embodiment of the present invention, the sorbitol may be 0.2-2.0 parts by weight, more preferably 0.5-1.5 parts by weight, more preferably 0.8-1.2 parts by weight, and most preferably 1.0 parts by weight.

[0065] In a preferred embodiment of the present invention, the alanine may be 0.5-2.0 parts by weight, more preferably 0.8-1.6 parts by weight, more preferably 1.0-1.4 parts by weight, and most preferably 1.2 parts by weight.

[0066] In a preferred embodiment of the present invention, the hydroxypropyl cellulose may be 0.5-2.0 parts by weight, more preferably 0.5-1.5 parts by weight, more preferably 0.6-1.0 parts by weight, and most preferably 0.8 parts by weight.

[0067] In a preferred embodiment of the present invention, the sodium dihydrogen phosphate may be 1-3 parts by weight, more preferably 1.5-2.5 parts by weight, more preferably 1.8-2.2 parts by weight, and most preferably 2.0 parts by weight.

[0068] In a preferred embodiment of the present invention, the disodium hydrogen phosphate may be 5-7 parts by weight, more preferably 5.5-6.5 parts by weight, more preferably 5.8-6.2 parts by weight, and most preferably 6.0 parts by weight.

[0069] Representatively, the tobramycin eye drops of the present invention comprise:

[0070] Components Dosage Tobramycin 3.0 parts by weight Polyethylene glycol 400 2.0 parts by weight glycerin 1.5 parts by weight Sorbitol 1.0 part by weight alanine 1.2 parts by weight Hydroxypropyl cellulose 0.8 parts by weight Sodium dihydrogen phosphate 2.0 parts by weight disodium hydrogen phosphate 6.0 parts by weight; and water 1000 parts by weight.

[0071] Typically, the tobramycin eye drops comprise:

[0072]

[0073]

[0074] The tobramycin eye drops of the present invention can be prepared by a mixing method, for example, by mixing tobramycin, polyethylene glycol 400, glycerin, sorbitol, alanine, hydroxypropyl cellulose, sodium dihydrogen phosphate, disodium hydrogen phosphate and water to obtain the tobramycin eye drops.

[0075] The preferred method for preparing tobramycin eye drops according to the present invention includes the following steps:

[0076] Add 75-85% of the prescribed amount of water to a mixing tank. Under conditions of 35-45℃, add the prescribed amounts of polyethylene glycol 400, glycerin, sodium dihydrogen phosphate, and disodium hydrogen phosphate. After stirring and dissolving, add the prescribed amount of hydroxypropyl cellulose and stir and dissolve. Then add the prescribed amount of tobramycin and stir and dissolve to obtain a drug solution. Add the prescribed amounts of sorbitol and alanine to the drug solution and stir and dissolve. Add water to the drug solution to the volume required for preparation, filter, and obtain tobramycin eye drops.

[0077] The main superior technical effects of this invention include:

[0078] 1. This invention develops a tobramycin eye drop, which has the advantage of low irritation to ocular administration and can significantly improve ocular administration compliance.

[0079] 2. The tobramycin eye drops described in this invention have excellent light and high temperature stability, ensuring the stability of tobramycin eye drops during storage and transportation, guaranteeing drug quality, reducing storage and transportation costs, and thus effectively ensuring the safety of tobramycin eye drops.

[0080] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Experimental methods in the following embodiments that do not specify specific conditions are generally performed under conventional conditions.

[0081] Example 1: Tobramycin Eye Drops

[0082] The prescription for tobramycin eye drops in this Example 1 is shown in Table 1:

[0083] Table 1. Formulation of Tobramycin Eye Drops

[0084] Components Dosage Tobramycin 3.0g Polyethylene glycol 400 2.0g glycerin 1.5g Sorbitol 1.0g alanine 1.2g Hydroxypropyl cellulose 0.8g Sodium dihydrogen phosphate 2.0g disodium hydrogen phosphate 6.0g Add water for injection to 1000ml

[0085] Preparation method

[0086] Boiled and cooled 80% of the prescribed volume of water for injection was added to a mixing tank. At 40°C, the prescribed volumes of polyethylene glycol 400, glycerin, sodium dihydrogen phosphate, and disodium hydrogen phosphate were added and stirred until dissolved. Then, the prescribed volume of hydroxypropyl cellulose was added and stirred until dissolved. Finally, the prescribed volume of tobramycin was added and stirred until dissolved to obtain a drug solution. The prescribed volumes of sorbitol and alanine were added to the drug solution and stirred until dissolved. Boiled and cooled water for injection was added to the final volume. The solution was then filtered through 0.45 μm and 0.22 μm microporous membranes to obtain tobramycin eye drops, which were dispensed into transparent PET bottles. The tobramycin strength was 3 mg / ml.

[0087] Comparative Example 1: Tobramycin Eye Drops

[0088] The prescription for tobramycin eye drops in Comparative Example 1 is shown in Table 2:

[0089] Table 2. Formulation of Tobramycin Eye Drops

[0090] Components Dosage Tobramycin 3.0g Polyethylene glycol 400 2.0g glycerin 0.4g Sorbitol 1.0g alanine 1.2g Hydroxypropyl cellulose 0.6g Sodium dihydrogen phosphate 2.0g disodium hydrogen phosphate 6.0g Add water for injection to 1000ml

[0091] Preparation method

[0092] Boiled and cooled 80% of the prescribed volume of water for injection was added to a mixing tank. At 40°C, the prescribed volumes of polyethylene glycol 400, glycerin, sodium dihydrogen phosphate, and disodium hydrogen phosphate were added and stirred until dissolved. Then, the prescribed volume of hydroxypropyl cellulose was added and stirred until dissolved. Finally, the prescribed volume of tobramycin was added and stirred until dissolved to obtain a drug solution. The prescribed volumes of sorbitol and alanine were added to the drug solution and stirred until dissolved. Boiled and cooled water for injection was added to the final volume. The solution was then filtered through 0.45 μm and 0.22 μm microporous membranes to obtain tobramycin eye drops, which were dispensed into transparent PET bottles. The tobramycin strength was 3 mg / ml.

[0093] Comparative Example 2: Tobramycin Eye Drops

[0094] The prescription for tobramycin eye drops in Comparative Example 2 is shown in Table 3:

[0095] Table 3. Formulation of Tobramycin Eye Drops

[0096] Components Dosage Tobramycin 3.0g Polyethylene glycol 400 0.6g glycerin 1.5g Sorbitol 1.0g alanine 1.0g Hydroxypropyl cellulose 0.8g Sodium dihydrogen phosphate 2.0g disodium hydrogen phosphate 6.0g Add water for injection to 1000ml

[0097] Preparation method

[0098] Boiled and cooled 80% of the prescribed volume of water for injection was added to a mixing tank. At 40°C, the prescribed volumes of polyethylene glycol 400, glycerin, sodium dihydrogen phosphate, and disodium hydrogen phosphate were added and stirred until dissolved. Then, the prescribed volume of hydroxypropyl cellulose was added and stirred until dissolved. Finally, the prescribed volume of tobramycin was added and stirred until dissolved to obtain a drug solution. The prescribed volumes of sorbitol and alanine were added to the drug solution and stirred until dissolved. Boiled and cooled water for injection was added to the final volume. The solution was then filtered through 0.45 μm and 0.22 μm microporous membranes to obtain tobramycin eye drops, which were dispensed into transparent PET bottles. The tobramycin strength was 3 mg / ml.

[0099] Comparative Example 3: Tobramycin Eye Drops

[0100] The prescription for tobramycin eye drops in Comparative Example 3 is shown in Table 4:

[0101] Table 4. Formulation of Tobramycin Eye Drops

[0102] Components Dosage Tobramycin 3.0g Polyethylene glycol 400 2.0g glycerin 1.5g Sorbitol 1.0g Hydroxypropyl cellulose 0.8g Sodium dihydrogen phosphate 2.0g disodium hydrogen phosphate 6.0g Add water for injection to 1000ml

[0103] Preparation method

[0104] Boiled and cooled 80% of the prescribed volume of water for injection was added to a mixing tank. At 40°C, the prescribed volumes of polyethylene glycol 400, glycerin, sodium dihydrogen phosphate, and disodium hydrogen phosphate were added and stirred until dissolved. Then, the prescribed volume of hydroxypropyl cellulose was added and stirred until dissolved. Finally, the prescribed volume of tobramycin was added and stirred until dissolved to obtain a drug solution. The prescribed volume of sorbitol was added to the drug solution and stirred until dissolved. Boiled and cooled water for injection was added to the final volume. The solution was then filtered through 0.45 μm and 0.22 μm microporous membranes to obtain tobramycin eye drops, which were dispensed into transparent PET bottles. The tobramycin strength was 3 mg / ml.

[0105] Comparative Example 4: Tobramycin Eye Drops

[0106] The prescription for tobramycin eye drops in Comparative Example 4 is shown in Table 5:

[0107] Table 5. Formulation of Tobramycin Eye Drops

[0108] Components Dosage Tobramycin 3.0g glycerin 1.5g Sorbitol 1.0g alanine 1.2g Hydroxypropyl cellulose 0.8g Sodium dihydrogen phosphate 2.0g disodium hydrogen phosphate 6.0g Add water for injection to 1000ml

[0109] Preparation method

[0110] Boiled and cooled 80% of the prescribed amount of water for injection was added to a mixing tank. At 40°C, the prescribed amounts of glycerol, sodium dihydrogen phosphate, and disodium hydrogen phosphate were added and stirred until dissolved. Then, the prescribed amount of hydroxypropyl cellulose was added and stirred until dissolved. Finally, the prescribed amount of tobramycin was added and stirred until dissolved to obtain a drug solution. The prescribed amounts of sorbitol and alanine were added to the drug solution and stirred until dissolved. Boiled and cooled water for injection was added to the final volume. The solution was then filtered through 0.45 μm and 0.22 μm microporous membranes to obtain tobramycin eye drops, which were dispensed into transparent PET bottles. The tobramycin strength was 3 mg / ml.

[0111] Evaluation of formulation efficacy

[0112] 1. Eye irritation assessment

[0113] Healthy white rabbits were randomly divided into 5 groups (n=10). One drop of tobramycin eye drops prepared in Example 1, Comparative Example 1, Comparative Example 2, Comparative Example 3, or Comparative Example 4 was instilled into the left eye of each group, while one drop of physiological saline was instilled into the right eye as a control. This was done once daily for 10 consecutive days. The irritation of the eyes by the tobramycin eye drops was observed 1 hour after the first instillation and 1 hour after the 10th instillation using sodium fluorescein staining and slit-lamp examination.

[0114] The evaluation items and their scores for eye stimulation level are as follows:

[0115] Cornea: 0 points - no opacity; 1 point - scattered or diffuse opacity, iris clearly visible; 2 points - translucent area easily distinguishable, iris blurry; 3 points - grayish-white translucent area appears, iris details are unclear, pupil size barely visible; 4 points - cornea opaque, iris unrecognizable.

[0116] Iris: 0 points - normal; 1 point - significantly deepened folds, congestion, swelling, mild congestion around the cornea, pupil still responds to light; 2 points - hemorrhage / visible necrosis / no response to light (or one of these).

[0117] Conjunctival hyperemia (referring to palpebral and bulbar conjunctiva): 0 points - normal blood vessels; 1 point - bright red blood vessels; 2 points - dark red blood vessels, which are difficult to distinguish; 3 points - diffuse hyperemia, which is purplish-red.

[0118] Edema: 0 points - no edema; 1 point - mild edema (including eyelids); 2 points - significant edema with partial eyelid eversion; 3 points - edema extending to the eyelid to half-closed; 4 points - edema extending to the eyelid beyond half-closed;

[0119] Discharge: 0 points - no discharge; 1 point - small amount of discharge; 2 points - discharge makes the eyelids and eyelashes moist or sticky; 3 points - discharge makes the entire eye area moist or sticky.

[0120] The total score for eye irritation assessment and its corresponding evaluation criteria are as follows:

[0121] Non-irritating: 0-3 (inclusive of 0 but exclusive of 3) points;

[0122] Mild irritation: 3-8 (inclusive of 3 but exclusive of 8) points;

[0123] Moderate irritation: 8-12 (inclusive of 8 but exclusive of 12) points;

[0124] Severe irritation: 12-16 (inclusive) points.

[0125] The results of the ocular irritation evaluation of the tobramycin eye drops prepared in Example 1 and Comparative Examples 1-4 are shown in Table 6.

[0126] Table 6. Evaluation of ocular irritation of tobramycin eye drops.

[0127]

[0128] As can be seen from Table 6, the tobramycin eye drops prepared in Example 1 are non-irritating to the eyes. Therefore, the tobramycin eye drops prepared in Example 1 have excellent ocular administration compliance.

[0129] 2. Stability assessment

[0130] 2.1 Light stability test

[0131] In accordance with the guidelines for stability testing of preparations in the Chinese Pharmacopoeia, the tobramycin eye drops prepared in Example 1 and Comparative Examples 1-4, dispensed in transparent PET bottles, were placed under light conditions (4500 lx, 25°C) for 0, 5, and 10 days. At different time points, the tobramycin and maximum single impurity (impurity) content of the tobramycin eye drops were determined by high performance liquid chromatography (HPLC) to investigate the light stability of the tobramycin eye drops prepared in Example 1 and Comparative Examples 1-4. The results are shown in Table 7.

[0132] Table 7. Stability study of tobramycin eye drops prepared in Example 1 and Comparative Examples 1-4 under light conditions (4500 lx, 25 °C).

[0133]

[0134] Note: "—" indicates that precipitation has occurred and no measurement is required.

[0135] As can be seen from Table 7, the tobramycin eye drops prepared in Example 1 have excellent stability under light, thereby reducing storage and transportation costs. The tobramycin eye drops prepared in Example 1 can be dispensed into transparent containers, reducing production costs. Furthermore, the properties of the dispensed tobramycin eye drops (such as whether there is precipitation, discoloration, etc.) can be quickly and effectively observed through the transparent containers before use, thereby ensuring medication safety.

[0136] 2.2 Accelerated Stability Assessment

[0137] In accordance with the guidelines for stability testing of preparations in the Chinese Pharmacopoeia, the tobramycin eye drops prepared in Example 1, dispensed in transparent PET bottles, were placed at a temperature of 40±2℃ and a relative humidity of RH 75±5% for 0 days, 1, 3, and 6 months. At different time points, the tobramycin and maximum single impurity (impurity) content of the tobramycin eye drops were determined by high performance liquid chromatography (HPLC) to investigate the light stability of the tobramycin eye drops prepared in Example 1. The results are shown in Table 8.

[0138] Table 8. Stability study of tobramycin eye drops prepared in Example 1 at 40±2℃ and relative humidity RH 75±5%.

[0139]

[0140]

[0141] As can be seen from Table 8, the tobramycin eye drops prepared in Example 1 have excellent accelerated stability, which can ensure the storage and transportation stability of tobramycin eye drops, ensure drug quality, reduce storage and transportation costs, and thus effectively ensure the safety of tobramycin eye drops.

[0142] The above description is an implementation scheme designed for one case of the present invention. It should be noted that for those skilled in the art, several improvements can be made without departing from the principle of the present invention, and these improvements should also be considered within the scope of protection of the present invention.

Claims

1. A tobramycin eye drop, characterized in that, The tobramycin eye drops described herein consist of the following components:

2. The tobramycin eye drops as described in claim 1, characterized in that, The tobramycin eye drops described herein consist of the following components:

3. A method for preparing tobramycin eye drops as described in claim 1, characterized in that, The method includes the following steps: The tobramycin eye drops were obtained by mixing tobramycin, polyethylene glycol 400, glycerin, sorbitol, alanine, hydroxypropyl cellulose, sodium dihydrogen phosphate, disodium hydrogen phosphate, and water.

4. A medicine box comprising tobramycin eye drops as described in claim 1.

5. Use of the tobramycin eye drops as described in claim 1 in the preparation of a medicament for treating localized infections of the external eye and its appendages caused by bacteria.

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