CN118121709A - Ophthalmic pharmaceutical composition, and preparation method and application thereof - Google Patents

Abstract

The invention relates to the technical field of medicaments, in particular to a medicament for treating eye diseases, which relates to a medicament composition for treating eye diseases, a preparation method and application thereof, and comprises the components of an cyclooxygenase inhibitor, a quinolone antibiotic, a solubilizer, a thickener, a bacteriostat, a buffering agent, a pH regulator, an osmotic pressure regulator and a solvent; the method comprises the following steps: the materials are crushed, mixed, homogenized and stirred, and the composition is mainly used for treating keratitis. The bromfenac sodium can effectively eliminate inflammation, and the quinolone antibiotics can inhibit the growth of the following bacteria: the combination of the two drugs can play a synergistic effect to heal bacterial eye infection more quickly.

Description

Ophthalmic pharmaceutical composition, and preparation method and application thereof

Technical Field

The invention relates to the technical field of medicines, relates to a medicine for treating eye diseases, and relates to a medicine composition for eyes, a preparation method and application thereof.

Background

Ocular infections are often accompanied by inflammation of the eye and even surrounding tissues, and ophthalmic surgery or ocular trauma often increases the risk of bacterial infection and inflames the tissues at the affected site. Thus, a single formulation of a compound formulation of one or more antibiotics with anti-infective use and one or more steroidal or non-carrier anti-inflammatory agents with anti-inflammatory effect is desirable.

Keratitis is a common inflammation of eye diseases, and is a corneal inflammatory lesion caused by trauma or bacteria, viruses and fungi infection, including herpes simplex keratitis, superficial punctate keratitis, corneal degeneration, suppurative keratitis, keratomatrix inflammation, beam keratitis and the like, and the corneal inflammation inevitably leads to more or less influenced vision, especially the condition that the inflammation invades the pupil area is more serious. The eyes have foreign body sensation, stinging and even burning sensation. Mixed hyperemia of the bulbar conjunctiva surface is accompanied by symptoms such as photophobia, lacrimation, vision disorder and increased secretion. At present, medicines and operation treatments are generally used for treating the keratitis, and the medicines are mainly antibiotics, but no satisfactory broad-spectrum antibacterial agent exists at present, and meanwhile, the side effects of the antibiotics are great after long-term use; secondly, the operation treatment is carried out, and the risk of the operation treatment is relatively high due to the accurate eye structure. There is therefore a need to develop new drugs to overcome the above problems.

Disclosure of Invention

The invention aims at the problems and provides an ophthalmic pharmaceutical composition, a preparation method and application thereof.

In order to achieve the aim, the invention adopts the technical proposal that,

An ophthalmic pharmaceutical composition is characterized by comprising the following components in detail:

Preferably, the composition further comprises the following components:

proper amount of pH regulator

And an appropriate amount of osmotic pressure regulator.

Preferably, the cyclooxygenase inhibitor is sodium bromfenac.

Preferably, the quinolone antibiotics comprise any one of gatifloxacin, enoxacin, ciprofloxacin hydrochloride, norfloxacin hydrochloride, lomefloxacin hydrochloride, levofloxacin hydrochloride, moxifloxacin hydrochloride, ofloxacin hydrochloride and tosufloxacin tosylate.

Preferably, the solubilizer comprises any one of potassium aluminum sulfate dodecahydrate and polysorbate 20; the thickener comprises carboxymethyl cellulose; the bacteriostatic agent comprises benzalkonium chloride.

Preferably, the pH regulator is sodium hydroxide or/and hydrochloric acid, and the ratio of the pH regulator to the hydrochloric acid is 0.02% -0.05%: the osmotic pressure regulator is sodium chloride, and the ratio is: 0.8% -1.0%.

Preferably, the solvent is sterilized water for injection.

A method of ophthalmic pharmaceutical composition, comprising in particular the following method:

A. respectively weighing bromfenac sodium and quinolone antibiotics, and crushing to D90 less than 10-20 μm;

B. Placing the beaker on a stirrer, adding a proper amount of sterilization injection water and a thickener, stirring and dissolving, adding a solubilizer, stirring for a certain time, adding a prescribed amount of sodium bromfenac, stirring to be uniform, and filtering;

C. Starting a high-speed homogenizer to homogenize the solution for 5min, and cooling to room temperature to obtain a pale yellow solution 1;

D. Placing the other beaker in a water bath kettle, setting the temperature to 55+/-2 ℃, stirring at the speed of 30 revolutions per minute, adding a proper amount of sterilizing water for injection and a solubilizer, stirring for 20 minutes, adding quinolone antibiotics, adding borax, sodium chloride and benzalkonium chloride, and continuously stirring to room temperature to obtain a solution 2;

E. adding the solution 2 into the solution 1 under the stirring state at room temperature, continuously stirring, starting high-speed homogenization for 5min at intervals of 10min, and stirring for 40min in total;

F. After the pH value is regulated to 5-7 by the pH regulator, the pH value is measured again after the volume is fixed;

G. Filling into eye drop bottle, 5 ml/bottle, and labeling.

The application of the ophthalmic medicine composition prepared by the preparation method thereof in treating keratitis in eyes.

Compared with the prior art, the invention has the advantages and positive effects that,

The bromfenac sodium can effectively eliminate inflammation, and the quinolone antibiotics can inhibit the growth of the following bacteria: the combination of the two drugs can play a synergistic effect to heal bacterial eye infection more quickly.

Detailed Description

In order that the above objects, features and advantages of the application may be more clearly understood, a further description of the application will be provided with reference to the following examples. It should be noted that, without conflict, the embodiments of the present application and features in the embodiments may be combined with each other.

In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention, but the present invention may be practiced otherwise than as described herein, and therefore the present invention is not limited to the specific embodiments of the disclosure that follow.

An ophthalmic pharmaceutical composition comprises sodium bromfenac, quinolone antibiotics, a solubilizer, a thickener, a PH regulator, a bacteriostat, an osmotic pressure regulator and a solvent, namely, the eye drops can be prepared according to a certain proportion, and the following components are prepared according to the proportion relation:

the specific proportions of the composition and the relationship of the proportions to each other are clearly explained above.

Sodium bromfenac and quinolones are described with respect to the above description.

The bromfenac sodium is a 2-amino-3-benzoyl phenylacetic acid derivative, has a structural formula as shown in the specification, has a structure similar to ketoprofen and diclofenac, can inhibit the synthesis of prostaglandin inflammatory mediators mediated by cyclooxygenase, is one of the most effective cyclooxygenase inhibitors, has strong anti-inflammatory and analgesic effects, and has the action intensity which is 10 times that of other nonsteroidal anti-inflammatory drugs. The bromfenac sodium is developed into eye drops from Japanese Qianshou pharmacy, the specification is 5mL:5mg, and the bromfenac sodium is clinically used for symptomatic treatment of inflammatory diseases of external eyes and anterior eyes: blepharitis, conjunctivitis, jiang Moyan (including upper uveitis), postoperative inflammation, and the like.

Quinolones are synthetic antibacterial agents (structures shown below) having 4-quinolones (or praziquantels) as their basic structures. Different groups are introduced into the N1 position, the C5 position, the C6 position, the C7 position and the C8 position of the 4-quinolone mother nucleus to form the quinolone medicines with the characteristics.

The quinolone antibiotics act on bacterial DNA helicase to prevent bacterial DNA from forming supercoiled and damage chromosome, thereby playing a role in sterilization. It has the following characteristics: ① Has broad antibacterial spectrum, and has strong antibacterial effect on aerobic gram-negative bacillus. ② The internal distribution is wide, and the medicine concentration in tissue and body fluid is high. ③ The elimination half-life of the medicine is longer, and the medicine can be administrated for 1 to 2 times per day. ④ Most varieties are oral administration and injection, and the use is convenient. ⑤ Adverse reactions are mostly lighter, and serious adverse reactions are less frequent.

1.1 Example 1

Respectively weighing 0.52g of bromfenac sodium and 0.50g of gatifloxacin, and crushing until the D90 is 10 mu m;

Placing the beaker on a stirrer, adding a proper amount of sterilization injection water and 2.54g of hypromellose, stirring and dissolving, adding 0.63g of aluminum potassium sulfate dodecahydrate, stirring for a certain time, adding sodium bromfenate, stirring to be uniform, and filtering;

Starting a high-speed homogenizer to homogenize the solution for 5min, and cooling to room temperature to obtain a pale yellow solution 1;

placing the other beaker in a water bath kettle, setting the temperature at 56 ℃ and the stirring speed at 30 revolutions per minute, adding a proper amount of sterilizing injection water and 205.08g of polysorbate, stirring for 20 minutes, adding 1.56g of gatifloxacin, adding 0.52g of borax, 4.35g of sodium chloride and 0.26g of benzalkonium chloride, and continuously stirring to room temperature to obtain a solution 2;

Adding the solution 2 into the solution 1 under the stirring state at room temperature, continuously stirring, starting high-speed homogenization for 5min at intervals of 10min, and stirring for 40min in total;

the pH value is regulated to 6.78 by the pH regulator, and the pH value is measured again to 6.82 after the volume is fixed to 500 ml;

Filling into eye drop bottle, 5 ml/bottle, labeling, and batch number SE-2024-004-240105-01.

1.2 Example 2

Respectively weighing 0.51g of bromfenac sodium and 0.53g of enoxacin, and crushing until the D90 is 10 mu m;

Placing the beaker on a stirrer, adding a proper amount of sterilization injection water and 2.58g of hypromellose, stirring and dissolving, adding 0.64g of aluminum potassium sulfate dodecahydrate, stirring for a certain time, adding sodium bromfenate, stirring to be uniform, and filtering;

Starting a high-speed homogenizer to homogenize the solution for 5min, and cooling to room temperature to obtain a pale yellow solution 1;

Placing the other beaker in a water bath kettle, setting the temperature to be 56 ℃, stirring at the speed of 30 revolutions per minute, adding a proper amount of sterilization injection water and 205.09g of polysorbate, stirring for 20 minutes, adding 1.52g of gatifloxacin, adding 0.55g of borax, 4.30g of sodium chloride and 0.24g of benzalkonium chloride, and continuously stirring to room temperature to obtain a solution 2;

Adding the solution 2 into the solution 1 under the stirring state at room temperature, continuously stirring, starting high-speed homogenization for 5min at intervals of 10min, and stirring for 40min in total;

the pH value is regulated to 6.76 by the pH regulator, and the pH value is measured again to 6.76 after the volume is fixed to 500 ml;

Filling into eye drop bottle, 5 ml/bottle, labeling, and batch number SE-2024-004-240105-02.

1.3 Example 3

Respectively weighing 0.55g of bromfenac sodium and 0.57g of pazufloxacin mesylate (counted by pazufloxacin), and crushing until the D90 is 11 mu m;

Placing the beaker on a stirrer, adding a proper amount of sterilization injection water and 2.53g of hypromellose, stirring and dissolving, adding 0.66g of aluminum potassium sulfate dodecahydrate, stirring for a certain time, adding sodium bromfenate, stirring to be uniform, and filtering;

Starting a high-speed homogenizer to homogenize the solution for 5min, and cooling to room temperature to obtain a pale yellow solution 1;

Placing the other beaker in a water bath kettle, setting the temperature to 55 ℃, stirring at the speed of 30 revolutions per minute, adding a proper amount of sterilizing injection water and 205.07g of polysorbate, stirring for 20 minutes, adding 1.52g of gatifloxacin, adding 0.51g of borax, 4.34g of sodium chloride and 0.22g of benzalkonium chloride, and continuously stirring to room temperature to obtain a solution 2;

Adding the solution 2 into the solution 1 under the stirring state at room temperature, continuously stirring, starting high-speed homogenization for 5min at intervals of 10min, and stirring for 40min in total;

after the pH value is regulated to 6.83 by the pH regulator, the pH value is measured again to 6.89 after the volume is fixed to 500 ml;

filling into eye drop bottle, 5 ml/bottle, labeling, and batch number SE-2024-004-240105-03.

1.4 Example 4

Respectively weighing 0.50g of bromfenac sodium and 0.53g of ciprofloxacin hydrochloride (calculated by ciprofloxacin), and crushing to D90 of 11 mu m;

placing the beaker on a stirrer, adding a proper amount of sterilization injection water and 2.55g of hypromellose, stirring and dissolving, adding 0.6g of aluminum potassium sulfate dodecahydrate, stirring for a certain time, adding sodium bromfenate, stirring to be uniform, and filtering;

Starting a high-speed homogenizer to homogenize the solution for 5min, and cooling to room temperature to obtain a pale yellow solution 1;

Placing the other beaker in a water bath kettle, setting the temperature to 55 ℃, stirring at the speed of 30 revolutions per minute, adding a proper amount of sterilizing injection water and 205.03g of polysorbate, stirring for 20 minutes, adding 1.55g of gatifloxacin, adding 0.54g of borax, 4.34g of sodium chloride and 0.21g of benzalkonium chloride, and continuously stirring to room temperature to obtain a solution 2;

Adding the solution 2 into the solution 1 under the stirring state at room temperature, continuously stirring, starting high-speed homogenization for 5min at intervals of 10min, and stirring for 40min in total;

the pH value is regulated to 6.75 by the pH regulator, and the pH value is measured again to 6.78 after the volume is fixed to 500 ml;

Filling into eye drop bottle, 5 ml/bottle, labeling, and batch number SE-2024-004-240105-04.

1.5 Example 5

Respectively weighing 0.52g of bromfenac sodium and 0.53g of norfloxacin hydrochloride (calculated as norfloxacin), and crushing to D90 of 10 mu m;

Placing the beaker on a stirrer, adding a proper amount of sterilization injection water and 2.53g of hypromellose, stirring and dissolving, adding 0.67g of aluminum potassium sulfate dodecahydrate, stirring for a certain time, adding sodium bromfenate, stirring to be uniform, and filtering;

Starting a high-speed homogenizer to homogenize the solution for 5min, and cooling to room temperature to obtain a pale yellow solution 1;

placing the other beaker in a water bath kettle, setting the temperature to 55 ℃, stirring at the speed of 30 revolutions per minute, adding a proper amount of sterilizing injection water and 205.09g of polysorbate, stirring for 20 minutes, adding 1.54g of gatifloxacin, adding 0.55g of borax, 4.34g of sodium chloride and 0.28g of benzalkonium chloride, and continuously stirring to room temperature to obtain a solution 2;

Adding the solution 2 into the solution 1 under the stirring state at room temperature, continuously stirring, starting high-speed homogenization for 5min at intervals of 10min, and stirring for 40min in total;

after the pH value is regulated to 6.87 by the pH regulator, the pH value is measured again to 6.89 after the volume is fixed to 500 ml;

Filling into eye drop bottle, 5 ml/bottle, labeling, and batch number SE-2024-004-240105-05.

1.6 Example 6

Respectively weighing 0.56g of bromfenac sodium and 0.58g of lomefloxacin hydrochloride (calculated by lomefloxacin), and crushing to D90 of 10 mu m;

Placing the beaker on a stirrer, adding a proper amount of sterilization injection water and 2.53g of hypromellose, stirring and dissolving, adding 0.66g of aluminum potassium sulfate dodecahydrate, stirring for a certain time, adding sodium bromfenate, stirring to be uniform, and filtering;

Starting a high-speed homogenizer to homogenize the solution for 5min, and cooling to room temperature to obtain a pale yellow solution 1;

Placing the other beaker in a water bath kettle, setting the temperature to be 56 ℃, stirring at the speed of 30 revolutions per minute, adding a proper amount of sterilization injection water and 205.06g of polysorbate, stirring for 20 minutes, adding 1.54g of gatifloxacin, adding 0.56g of borax, 4.38g of sodium chloride and 0.21g of benzalkonium chloride, and continuously stirring to room temperature to obtain a solution 2;

Adding the solution 2 into the solution 1 under the stirring state at room temperature, continuously stirring, starting high-speed homogenization for 5min at intervals of 10min, and stirring for 40min in total;

after the pH value is regulated to 7.23 by the pH regulator, the pH value is measured again to 7.28 after the volume is fixed to 500 ml;

filling into eye drop bottle, 5 ml/bottle, labeling, and batch number SE-2024-004-240105-06.

1.7 Example 7

Respectively weighing 0.53g of bromfenac sodium and 0.58g of levofloxacin hydrochloride (calculated by the levofloxacin), and crushing to D90 of 10 mu m;

Placing the beaker on a stirrer, adding a proper amount of sterilization injection water and 2.57g of hypromellose, stirring and dissolving, adding 0.69g of aluminum potassium sulfate dodecahydrate, stirring for a certain time, adding sodium bromfenate, stirring to be uniform, and filtering;

Starting a high-speed homogenizer to homogenize the solution for 5min, and cooling to room temperature to obtain a pale yellow solution 1;

Placing the other beaker in a water bath kettle, setting the temperature to 55 ℃, stirring at the speed of 30 revolutions per minute, adding a proper amount of sterilizing injection water and 205.09g of polysorbate, stirring for 20 minutes, adding 1.52g of gatifloxacin, adding 0.54g of borax, 4.36g of sodium chloride and 0.21g of benzalkonium chloride, and continuously stirring to room temperature to obtain a solution 2;

Adding the solution 2 into the solution 1 under the stirring state at room temperature, continuously stirring, starting high-speed homogenization for 5min at intervals of 10min, and stirring for 40min in total;

after the pH value is regulated to 6.73 by the pH regulator, the pH value is measured again to 6.78 after the volume is fixed to 500 ml;

Filling into eye drop bottle, 5 ml/bottle, labeling, and batch number SE-2024-004-240105-07.

1.8 Example 8

Respectively weighing 0.52g of bromfenac sodium and 0.56g of moxifloxacin hydrochloride (calculated by moxifloxacin), and crushing until D90 is 10 mu m;

Placing the beaker on a stirrer, adding a proper amount of sterilization injection water and 2.55g of hypromellose, stirring and dissolving, adding 0.67g of aluminum potassium sulfate dodecahydrate, stirring for a certain time, adding sodium bromfenate, stirring to be uniform, and filtering;

Starting a high-speed homogenizer to homogenize the solution for 5min, and cooling to room temperature to obtain a pale yellow solution 1;

Placing the other beaker in a water bath kettle, setting the temperature to 55 ℃, stirring at the speed of 30 revolutions per minute, adding a proper amount of sterilizing injection water and 205.07g of polysorbate, stirring for 20 minutes, adding 1.53g of gatifloxacin, adding 0.51g of borax, 4.32g of sodium chloride and 0.20g of benzalkonium chloride, and continuously stirring to room temperature to obtain a solution 2;

Adding the solution 2 into the solution 1 under the stirring state at room temperature, continuously stirring, starting high-speed homogenization for 5min at intervals of 10min, and stirring for 40min in total;

after the pH value is regulated to 7.23 by the pH regulator, the pH value is measured again to 7.28 after the volume is fixed to 500 ml;

Filling into eye drop bottle, 5 ml/bottle, labeling, and batch number SE-2024-004-240105-08.

1.9 Example 9

Respectively weighing 0.53g of bromfenac sodium and 0.54g of ofloxacin hydrochloride (calculated by ofloxacin), and crushing to D90 of 12 mu m;

Placing the beaker on a stirrer, adding a proper amount of sterilization injection water and 2.52g of hypromellose, stirring and dissolving, adding 0.67g of aluminum potassium sulfate dodecahydrate, stirring for a certain time, adding sodium bromfenate, stirring to be uniform, and filtering;

Starting a high-speed homogenizer to homogenize the solution for 5min, and cooling to room temperature to obtain a pale yellow solution 1;

Placing the other beaker in a water bath kettle, setting the temperature to 55 ℃, stirring at the speed of 30 revolutions per minute, adding a proper amount of sterilizing water for injection and 205.10g of polysorbate, stirring for 20 minutes, adding 1.51g of gatifloxacin, adding 0.51g of borax, 4.35g of sodium chloride and 0.20g of benzalkonium chloride, and continuing stirring to room temperature to obtain a solution 2;

Adding the solution 2 into the solution 1 under the stirring state at room temperature, continuously stirring, starting high-speed homogenization for 5min at intervals of 10min, and stirring for 40min in total;

after the pH value is regulated to 7.23 by the pH regulator, the pH value is measured again to 7.28 after the volume is fixed to 500 ml;

filling into eye drop bottle, 5 ml/bottle, labeling, and batch number SE-2024-004-240105-09.

1.10 Example 10

Respectively weighing 0.51g of bromfenac sodium and 0.57g of tosufloxacin tosylate (counted by tosufloxacin), and crushing to D90 of 15 mu m;

Placing the beaker on a stirrer, adding a proper amount of sterilization injection water and 2.50g of hypromellose, stirring and dissolving, adding 0.66g of aluminum potassium sulfate dodecahydrate, stirring for a certain time, adding sodium bromfenate, stirring to be uniform, and filtering;

Starting a high-speed homogenizer to homogenize the solution for 5min, and cooling to room temperature to obtain a pale yellow solution 1;

Placing the other beaker in a water bath kettle, setting the temperature to be 56 ℃, stirring at the speed of 30 revolutions per minute, adding a proper amount of sterilization injection water and 205.01g of polysorbate, stirring for 20 minutes, adding 1.54g of gatifloxacin, adding 0.58g of borax, 4.32g of sodium chloride and 0.21g of benzalkonium chloride, and continuously stirring to room temperature to obtain a solution 2;

Adding the solution 2 into the solution 1 under the stirring state at room temperature, continuously stirring, starting high-speed homogenization for 5min at intervals of 10min, and stirring for 40min in total;

the pH value is regulated to 6.82 by the pH regulator, and the pH value is measured again to 6.85 after the volume is fixed to 500 ml;

filling into eye drop bottle, 5 ml/bottle, labeling, and batch number SE-2024-004-240105-10.

The physicochemical properties of the products prepared in the above examples were examined as follows:

The products obtained in the above examples were subjected to in vitro release assay (phosphate as vehicle at pH 7.0) as follows:

according to the prepared sample, the invention provides an animal drug effect evaluation test, which comprises the following steps:

New Zealand rabbits are selected as a test system, under the local anesthesia of the tetracaine eye drops, an eyelid opener is used for fully opening the eyelid, a 7-cornel trephine is used for lightly pressing the cornea in the clockwise direction, so that the cornea is subjected to annular damage, and the depth is better than that of a front elastic layer. The liquid was pipetted into 2X 109/ml of Pseudomonas aeruginosa droplets onto the cornea, 0.1ml per eye, and the left eye was infected, and the right eye was left untreated. After 3d of film formation, the animals were divided into 7 experimental groups, which were a blank control group, a model group, a positive control group and the administration groups of examples 1 to 10, each group comprising 6 animals, according to the eye symptom score balance. The administration is started after grouping, and the corresponding test product or control product is administered to the left eye of each group of animals for test product, 4 times per day, and 2 drops each time. The model group and the blank group were given an equal volume of physiological saline.

After the samples of the different examples are dosed, the eyeball secretion, more ulcers and red swelling of the New Zealand rabbits are obviously reduced after 72 hours of film formation, wherein the effect of the group of the example 1 is most obvious, the self-administration is started for 6d, and obvious differences (p < 0.05 or p is less than 0.01) appear compared with the scores of the model group; the effects of example 7 and example 8 were minor, starting from self-administration 9d, with significant differences (p < 0.05) compared to the model group scores, but with higher scores than the example 1 group; the eye scores were also somewhat reduced for the remaining example groups, but there was no significant difference (p > 0.05) compared to the model group.

Bacterial keratitis rabbit weight

Group of	Body weight (kg)
		Normal control group	3.0±0.1
Model group	2.9±0.1
		Positive control group (levofloxacin eye drops)	3.0±0.1
Example 1	3.0±0.1
		Example 2	3.0±0.1
Example 3	3.1±0.1
		Example 4	2.9±0.1
Example 5	3.0±0.1
		Example 6	2.9±0.1
Example 7	2.9±0.1
		Example 8	2.9±0.1
Example 9	3.0±0.1
		Example 10	2.9±0.1

Note that: p > 0.05, compared to model group.

Bacterial keratitis rabbit eye observation score

Note that: * p < 0.05, < p < 0.01, compared to model group; p > 0.05, and the test sample group is compared with the positive control group.

The present invention is not limited to the above-mentioned embodiments, and any equivalent embodiments which can be changed or modified by the technical content disclosed above can be applied to other fields, but any simple modification, equivalent changes and modification made to the above-mentioned embodiments according to the technical substance of the present invention without departing from the technical content of the present invention still belong to the protection scope of the technical solution of the present invention.

Claims (9)

1. An ophthalmic pharmaceutical composition is characterized by comprising the following components in detail:

2. the ophthalmic pharmaceutical composition of claim 1, further comprising the following components:

proper amount of pH regulator

And an appropriate amount of osmotic pressure regulator.

3. An ophthalmic pharmaceutical composition according to claim 2, wherein the cyclooxygenase inhibitor is sodium bromfenac.

4. An ophthalmic pharmaceutical composition according to claim 3, wherein the quinolone antibiotic comprises any one of gatifloxacin, enoxacin, ciprofloxacin hydrochloride, norfloxacin hydrochloride, lomefloxacin hydrochloride, levofloxacin hydrochloride, moxifloxacin hydrochloride, ofloxacin hydrochloride, tosufloxacin tosylate.

5. An ophthalmic pharmaceutical composition according to claim 4, wherein the solubilizing agent comprises any one of potassium aluminum sulfate dodecahydrate, polysorbate 20; the thickener comprises carboxymethyl cellulose; the bacteriostatic agent comprises benzalkonium chloride.

6. The ophthalmic pharmaceutical composition according to claim 5, wherein the pH adjuster is sodium hydroxide or/and hydrochloric acid, and the ratio of the pH adjuster to the hydrochloric acid is 0.02% -0.05%: the osmotic pressure regulator is sodium chloride, and the ratio is: 0.8% -1.0%.

7. The ophthalmic pharmaceutical composition of claim 6 wherein the solvent is sterile water for injection.

8. A process for preparing an ophthalmic pharmaceutical composition according to any one of claims 1 to 7, characterized in that it comprises in particular the following process:

A. respectively weighing bromfenac sodium and quinolone antibiotics, and crushing to D90 less than 10-20 μm;

B. Placing the beaker on a stirrer, adding a proper amount of sterilization injection water and a thickener, stirring and dissolving, adding a solubilizer, stirring for a certain time, adding a prescribed amount of sodium bromfenac, stirring to be uniform, and filtering;

C. Starting a high-speed homogenizer to homogenize the solution for 5min, and cooling to room temperature to obtain a pale yellow solution 1;

D. the other beaker is placed in a water bath kettle, the temperature is set to 55+/-2 ℃, the stirring speed is 30 revolutions per minute,

Adding appropriate amount of sterilized injectable water and solubilizer, stirring for 20min, adding quinolone antibiotics,

Borax, sodium chloride and benzalkonium chloride are added, and stirring is continued to room temperature, so as to obtain a solution 2;

E. Adding the solution 2 into the solution 1 under stirring at room temperature, continuously stirring for 10min at intervals,

Starting one-time high-speed homogenization for 5min, and stirring for 40min in total;

F. After the pH value is regulated to 5-7 by the pH regulator, the pH value is measured again after the volume is fixed;

G. Filling into eye drop bottle, 5 ml/bottle, and labeling.

9. Use of an ophthalmic pharmaceutical composition prepared by the preparation method of any one of claims 1 to 8 in the treatment of keratitis, a disease in the eye.