Drug composition, its preparation method and application

Abstract

A pharmaceutical composition, its preparation method and application. The pharmaceutical composition includes the compound represented by formula I, hydroxypropyl methylcellulose, benzalkonium chloride and a pH adjuster as ingredients. The pharmaceutical composition is used to prepare a drug for preventing or treating cataract. The pharmaceutical composition has good light irradiation and high temperature stability, can be stored at room temperature, is convenient for patients to use, has a pH and osmotic pressure close to the intraocular environment, has a uniform particle size distribution, and can provide good comfort to patients.

Description

[Technical Field]

[0001] The present invention belongs to the field of medicine, specifically to a drug composition, its preparation method and application. [Background technology]

[0002] Cataracts are an ocular disease that develops in the lens inside the eye. Clouding of the lens is collectively referred to as cataract. Aging, genetics, metabolic disorders, trauma, radiation, poisoning, and local malnutrition can all damage the lens capsule, increasing its permeability and loss of its barrier function, leading to metabolic disorders in the lens and denaturing lens proteins, resulting in clouding. When the lens of the eye changes from transparent to opaque, affecting the eye's ability to absorb light, it impacts vision. Mild clouding of the eye has little impact on vision, but as the clouding progresses, vision declines and, in severe cases, can lead to blindness. Cataracts are one of the most common blinding diseases and a major cause of blindness. Because the mechanism of cataract formation is still unclear, no breakthroughs have been achieved in drug treatments. Therefore, surgical treatment is currently the only proven and effective treatment.

[0003] Although continuous advances in cataract surgery techniques have provided great support for cataract treatment, the cure rate of surgical treatment is still far lower than the incidence rate, and serious complications may occur. Meanwhile, the cost of cataract surgery is very high, placing a heavy burden on patients and the medical insurance system. Therefore, drug prevention and treatment play a very important role.

[0004] Currently, clinically available cataract treatments include (1) aldose reductase inhibitors such as Catalin, Phacolysin, and Bendazac Lysine; (2) antioxidants such as glutathione, taurine, and aspirin; (3) nutritional metabolism drugs such as vitamins and carotenoids; and (4) traditional Chinese herbal combinations such as Dendrobium Night-Light Pill, Qijudihuang Pill, and Shijueming San. However, long-term clinical trials have demonstrated that these cataract treatment drugs can only delay the progression of cataract symptoms and are unable to reverse the condition and treat cataracts. Therefore, there is a great need for new topical ophthalmic anti-cataract drugs that are clinically safe, have good therapeutic effects, have strong intraocular penetration, and have stable properties.

[0005] Lanosterol, an amphiphilic molecule concentrated in the lens, is synthesized by a key cyclization reaction in the cholesterol synthesis pathway of lanosterol synthase (LSS). It can reduce abnormal lens protein aggregation and reorganize it, restoring crystal clarity. Studies have demonstrated that lanosterol synthase can be detected in the lens. Furthermore, in a study of Shumiya cataract rats, a specific combination of homozygous mutations in lanosterol synthase and farnesyl diphosphate farnesyltransferase 1 (FDFT1) reduced cholesterol levels in the lens and caused cataracts. Lanosterol can significantly reduce preformed lens protein aggregates in vitro and at the cellular level. Lanosterol can also reverse cataract pathology in vivo, clearing and transparentizing the lens, demonstrating its potential as a novel molecule for preventing and treating cataracts.

[0006] WO2020177714 discloses a pharmaceutical formulation of a lanosterol prodrug compound that can alleviate cataract symptoms and improve lens transparency and lens GSH-PX activity. However, the formulation was found to require complex processing, poor stability, be difficult to store at room temperature, and be uncomfortable for patients to use. Therefore, clinically, there is a need to develop a composition or formulation that is simple to process, has strong formulation stability, and is comfortable for patients. Summary of the Invention [Problem to be solved by the invention]

[0007] In view of the shortcomings of the prior art, the present invention aims to provide a pharmaceutical composition, its preparation method and application, which has good stability under light irradiation and high temperature and can be used to prepare drugs for preventing or treating cataracts or floaters. [Means for solving the problem]

[0008] To achieve this goal, the present invention adopts the following technical solutions.

[0009] In a first aspect, the present invention provides a method for producing a medicament for the treatment of a pulmonary arthritis, comprising: A pharmaceutical composition is provided which contains, as ingredients, a compound represented by formula I, hydroxypropylmethylcellulose, benzalkonium chloride, and a pH adjuster. [ka]

[0010] The present inventors have found through investigation that by blending the compound of formula I with hydroxypropylmethylcellulose (HPMC), benzalkonium chloride and a pH adjuster, the stability of the compound of formula I can be significantly improved, and a pharmaceutical composition of stable quality can be obtained.

[0011] In some embodiments of the present invention, the drug composition comprises, as ingredients, in parts by weight: It contains 0.01 to 4 parts of a compound represented by formula I (for example, 0.01 parts, 0.05 parts, 0.1 parts, 0.3 parts, 0.5 parts, 0.8 parts, 1 part, 1.5 parts, 2 parts, 2.5 parts, 3 parts, 3.5 parts, or 4 parts, etc.), 2 to 12 parts of hydroxypropyl methylcellulose (for example, 2 parts, 3 parts, 5 parts, 8 parts, 10 parts, or 12 parts, etc.), 0.05 to 0.06 parts of benzalkonium chloride (for example, 0.05 parts, 0.052 parts, 0.053 parts, 0.055 parts, 0.056 parts, 0.058 parts, or 0.06 parts, etc.), and 1 to 20 parts of a pH adjuster (for example, 1 part, 2 parts, 3 parts, 5 parts, 8 parts, 10 parts, 12 parts, 15 parts, 18 parts, or 20 parts, etc.).

[0012] The pH of the drug composition is 6 to 8, for example, 6, 6.2, 6.5, 6.8, 7, 7.2, 7.5, 7.8, or 8.

[0013] In some embodiments of the present invention, the concentration of the compound of Formula I in the pharmaceutical composition is 0.01-4 mg / mL, preferably 0.1 mg / mL, 0.2 mg / mL, 0.3 mg / mL, 0.4 mg / mL, 0.5 mg / mL, 1 mg / mL, 2 mg / mL, 3 mg / mL, or 4 mg / mL.

[0014] In some embodiments of the present invention, the pH adjuster is one or a combination of at least two selected from sodium hydroxide, hydrochloric acid, sodium citrate, citric acid, boric acid, borax, sodium dihydrogen phosphate, disodium hydrogen phosphate, potassium dihydrogen phosphate, and dipotassium hydrogen phosphate.

[0015] In some embodiments of the invention, the drug composition further comprises a solubilizing agent.

[0016] In some embodiments of the present invention, the amount of solubilizer in the drug composition is 10 to 50 parts by weight, such as 10 parts, 15 parts, 20 parts, 25 parts, 30 parts, 35 parts, 40 parts, 45 parts, or 50 parts.

[0017] In some embodiments of the present invention, the solubilizer is one or a combination of at least two selected from polysorbate-80, glycerin, hydrogenated castor oil-RH40, polyethylene glycol 400, hydroxypropyl-β-cyclodextrin, and poloxamer 188.

[0018] In some embodiments of the present invention, the drug composition comprises, as ingredients, in parts by weight: 2 parts of the compound of formula I, 6 parts of hydroxypropyl methylcellulose, 16.5 parts of boric acid, 2 parts of borax, and 0.05 parts of benzalkonium chloride, Or 2 parts of the compound of formula I, 6 parts of hydroxypropyl methylcellulose, 40 parts of polysorbate-80, 16 parts of boric acid, 1.6 parts of borax, and 0.05 parts of benzalkonium chloride, Or, 2 parts of a compound of formula I, 6 parts of hydroxypropyl methylcellulose, 10 parts of hydrogenated castor oil-RH40, 17 parts of boric acid, 1.7 parts of borax, and 0.05 parts of benzalkonium chloride.

[0019] In a second aspect, the present invention provides a composition comprising, as components, in parts by weight: 2 parts of the compound of formula I, 6 parts of hydroxypropyl methylcellulose, 25 parts of glycerin and 0.05 parts of benzalkonium chloride, Alternatively, there is provided a pharmaceutical composition comprising 2 parts of the compound of formula I, 6 parts of hydroxypropyl methylcellulose, 10 parts of hydrogenated castor oil-RH40, 40 parts of polysorbate-80, 25 parts of glycerin, and 0.05 parts of benzalkonium chloride.

[0020] In some embodiments of the present invention, the particle size of the compound of formula I is <90 μm, preferably ≦50 μm.

[0021] In some embodiments of the present invention, the particle size distribution of the compound of Formula I is D90≦7 μm and / or D50≦4 μm.

[0022] In some embodiments of the present invention, D of the compound of formula I 90 The particle size is <8 μm.

[0023] In some embodiments of the present invention, D of the compound of formula I 50 The particle size is ≦3.5 μm.

[0024] In some embodiments of the present invention, the dosage form of the drug composition is a suspension, emulsion, or gel, preferably an emulsion.

[0025] In a third aspect, the present invention provides a method for preparing a pharmaceutical composition according to the first or second aspect, comprising uniformly mixing a compound of Formula I, hydroxypropylmethylcellulose, benzalkonium chloride, optionally a pH adjuster, and optionally a solubilizer in prescribed amounts to obtain the pharmaceutical composition.

[0026] In the present invention, the term "optionally" means that the corresponding component is present or absent. If the corresponding component is present in the drug composition, the corresponding component is used in the preparation method, and if the corresponding component is not present in the drug composition, the corresponding component is not used in the preparation method.

[0027] In some embodiments of the present invention, the preparation method comprises: Step (1) of dissolving hydroxypropyl methylcellulose in water for injection to obtain solution I; Step (2) of dissolving the ingredients other than hydroxypropylmethylcellulose and the compound represented by formula I in water for injection in the prescribed amounts, and then adding the solution to solution I and mixing uniformly to obtain solution II; Step (3) adding a prescribed amount of the compound represented by formula I to the solution II and mixing uniformly to obtain solution III; and (4) making up the solution III to the total volume with water for injection to obtain the pharmaceutical composition.

[0028] Preferably, the preparation method comprises: Step (1) dissolving hydroxypropyl methylcellulose in water for injection and stirring to completely dissolve to obtain solution I; Step (2) of dissolving the ingredients other than hydroxypropylmethylcellulose and the compound of formula I in water for injection in the prescribed amounts, and then adding the solution I, and adding water for injection until the amount reaches 90% of the prescribed amount, and stirring uniformly to obtain solution II; Step (3) adding a prescribed amount of a compound represented by formula I to said solution II to obtain solution III; Step (4) of homogenizing the solution III in a high-pressure homogenizer to obtain a solution IV; and (5) making up the solution IV to volume with water for injection to obtain the drug composition.

[0029] In a fourth aspect, the present invention provides the use of the pharmaceutical composition according to the first or second aspect in the preparation of a medicament for preventing or treating cataracts or floaters.

[0030] Compared with the prior art, the present invention has the following beneficial effects: The pharmaceutical composition provided by the present invention can be used for the prevention or treatment of cataracts and floaters, and even after being left for 10 days under light irradiation conditions of 4500 Lx or high temperature conditions of 60°C, the pH and osmotic pressure remain stable, and there are no significant changes in the related substances and contents. It has good stability under light irradiation and high temperature, can be stored at room temperature, and is convenient for patients to use. At the same time, the pH and osmotic pressure of the pharmaceutical composition are similar to the intraocular environment, the particle size distribution is uniform, and D 50 The particle size does not exceed 3.5 μm, which provides good patient comfort. DETAILED DESCRIPTION OF THE INVENTION

[0031] The technical solution of the present invention will be further described below by means of specific embodiments, which should be understood by those skilled in the art as being merely for the purpose of understanding the present invention and should not be regarded as a specific limitation on the present invention.

[0032] Example 1 This example provides a pharmaceutical composition containing the ingredients shown in the table below. [Table 1]

[0033] The method for preparing the drug composition described in this example is as follows: (1) First, hydroxypropyl methylcellulose was dissolved in 10% boiled water for injection, and an appropriate amount of cold water for injection was added and stirred to completely dissolve, thereby obtaining Solution I. (2) After stirring and dissolving the prescribed amounts of boric acid, borax, and benzalkonium chloride in an appropriate amount of water for injection, the solution was added to Solution I, and water for injection was added until the amount reached 90% of the prescribed amount. The mixture was stirred uniformly to obtain Solution II. (3) The compound represented by formula I was weighed in the prescribed amount and added to solution II, which was then dispersed uniformly in a high-shear emulsifier at a speed of 10,000 r / min for 10 minutes to obtain solution III. (4) Solution III was homogenized once in a high-pressure homogenizer at a pressure of 250 bar, the drug solution was collected, and the lines of the high-pressure homogenizer were washed with an appropriate amount of sterile water for injection. The washings were collected and combined with the drug solution to obtain Solution IV. (5) Dilute Solution IV to the full volume with sterile water for injection.

[0034] The pharmaceutical composition can be further sampled to measure the pH, osmolality, and content. After passing the test, the pharmaceutical composition can be prepared into an eye drop product by dispensing 5 mL of the pharmaceutical solution into each low-density polyethylene pharmaceutical eye drop bottle in a sterile environment.

[0035] Example 2 This example provides a pharmaceutical composition containing the ingredients shown in the table below. [Table 2]

[0036] The method for preparing the drug composition described in this example is as follows: (1) First, hydroxypropyl methylcellulose was dissolved in 10% boiled water for injection, and an appropriate amount of cold water for injection was added and stirred to completely dissolve, thereby obtaining Solution I. (2) After stirring and dissolving the prescribed amounts of boric acid, borax, and benzalkonium chloride in an appropriate amount of water for injection, add it to Solution I, gradually add the prescribed amount of polysorbate-80 while stirring, add water for injection until the amount reaches 90% of the prescribed amount, and stir uniformly to obtain Solution II. (3) The compound represented by formula I was weighed in the prescribed amount and added to solution II, which was then dispersed uniformly in a high-shear emulsifier at a speed of 10,000 r / min for 10 minutes to obtain solution III. (4) Solution III was homogenized once in a high-pressure homogenizer at a pressure of 250 bar, the drug solution was collected, and the lines of the high-pressure homogenizer were washed with an appropriate amount of sterile water for injection. The washings were collected and combined with the drug solution to obtain Solution IV. (5) Dilute Solution IV to the full volume with sterile water for injection.

[0037] The pharmaceutical composition can be further sampled to measure the pH, osmolality, and content. After passing the test, the pharmaceutical composition can be prepared into an eye drop product by dispensing 5 mL of the pharmaceutical solution into each low-density polyethylene pharmaceutical eye drop bottle in a sterile environment.

[0038] Example 3 This example provides a pharmaceutical composition containing the ingredients shown in the table below. [Table 3]

[0039] The method for preparing the drug composition described in this example is as follows: (1) First, hydroxypropyl methylcellulose was dissolved in 10% boiled water for injection, and an appropriate amount of cold water for injection was added and stirred to completely dissolve, thereby obtaining Solution I. (2) After stirring and dissolving the prescribed amounts of boric acid, borax, and benzalkonium chloride in an appropriate amount of water for injection, add it to Solution I, gradually add the prescribed amount of hydrogenated castor oil-RH40 while stirring, add water for injection until the amount reaches 90% of the prescribed amount, and stir evenly to obtain Solution II. (3) The compound represented by formula I was weighed in the prescribed amount and added to solution II, which was then dispersed uniformly in a high-shear emulsifier at a speed of 10,000 r / min for 10 minutes to obtain solution III. (4) Solution III was homogenized once in a high-pressure homogenizer at a pressure of 250 bar, the drug solution was collected, and the lines of the high-pressure homogenizer were washed with an appropriate amount of sterile water for injection. The washings were collected and combined with the drug solution to obtain Solution IV. (5) Dilute Solution IV to the full volume with sterile water for injection.

[0040] The pharmaceutical composition can be further sampled to measure the pH, osmolality, and content. After passing the test, the pharmaceutical composition can be prepared into an eye drop product by dispensing 5 mL of the pharmaceutical solution into each low-density polyethylene pharmaceutical eye drop bottle in a sterile environment.

[0041] Example 4 This example provides a pharmaceutical composition containing the ingredients shown in the table below. [Table 4]

[0042] The method for preparing the drug composition described in this example is as follows: (1) First, hydroxypropyl methylcellulose was dissolved in 10% boiled water for injection, and an appropriate amount of cold water for injection was added and stirred to completely dissolve, thereby obtaining Solution I. (2) After stirring and dissolving the prescribed amount of benzalkonium chloride in an appropriate amount of water for injection, add it to Solution I, gradually add the prescribed amount of glycerin while stirring, add water for injection until the amount becomes 90% of the prescribed amount, and stir evenly to obtain Solution II. (3) The compound represented by formula I was weighed in the prescribed amount and added to solution II, which was then dispersed uniformly in a high-shear emulsifier at a speed of 10,000 r / min for 10 minutes to obtain solution III. (4) Solution III was homogenized once in a high-pressure homogenizer at a pressure of 250 bar, the drug solution was collected, and the lines of the high-pressure homogenizer were washed with an appropriate amount of sterile water for injection. The washings were collected and combined with the drug solution to obtain Solution IV. (5) Dilute Solution IV to the full volume with sterile water for injection.

[0043] The pharmaceutical composition can be further sampled to measure the pH, osmolality, and content. After passing the test, the pharmaceutical composition can be prepared into an eye drop product by dispensing 5 mL of the pharmaceutical solution into each low-density polyethylene pharmaceutical eye drop bottle in a sterile environment.

[0044] Example 5 This example provides a pharmaceutical composition containing the ingredients shown in the table below. [Table 5]

[0045] The method for preparing the drug composition described in this example is as follows: (1) First, hydroxypropyl methylcellulose was dissolved in 10% boiled water for injection, and an appropriate amount of cold water for injection was added and stirred to completely dissolve, thereby obtaining Solution I. (2) After stirring and dissolving the prescribed amount of benzalkonium chloride in an appropriate amount of water for injection, add it to Solution I, and gradually add the prescribed amounts of hydrogenated castor oil-RH40, polysorbate-80, and glycerin while stirring. Add water for injection until the amount reaches 90% of the prescribed amount, and stir evenly to obtain Solution II. (3) The compound represented by formula I was weighed in the prescribed amount and added to solution II, which was then dispersed uniformly in a high-shear emulsifier at a speed of 10,000 r / min for 10 minutes to obtain solution III. (4) Solution III was homogenized once in a high-pressure homogenizer at a pressure of 250 bar, the drug solution was collected, and the lines of the high-pressure homogenizer were washed with an appropriate amount of sterile water for injection. The washings were collected and combined with the drug solution to obtain Solution IV. (5) Dilute Solution IV to the full volume with sterile water for injection.

[0046] The pharmaceutical composition can be further sampled to measure the pH, osmolality, and content. After passing the test, the pharmaceutical composition can be prepared into an eye drop product by dispensing 5 mL of the pharmaceutical solution into each low-density polyethylene pharmaceutical eye drop bottle in a sterile environment.

[0047] Comparative Example 1 A pharmaceutical composition is provided comprising the ingredients shown in the table below. [Table 6]

[0048] The preparation method of the drug composition is the same as that in Example 4, except that poloxamer 188 and poloxamer 407 are used instead of glycerin.

[0049] Stability testing (1) Light Irradiation Stability Test: The light irradiation stability of the compositions provided in the above Examples and Comparative Examples was examined, and all samples for which light irradiation factors were examined were packaged as commercially available products and placed in a light irradiation incubator MGC-100 under 4500 Lx conditions. Sampling was performed on days 0, 5, and 10, and measurements were performed according to the key stability considerations. The stability considerations included properties, particle size, particle size distribution, pH value, osmotic pressure, measurement of the content of the compound represented by Formula I, and measurement of the content of impurities, and the measurement results are shown in Table 1 below.

[0050] (2) High-Temperature Stability Test: To examine the high-temperature stability of the compositions provided in the above Examples and Comparative Examples, all samples for which high-temperature factors were examined were packaged as commercially available products and placed in a 101-1A digital electric heating dry thermostatic box at 60°C. Samples were taken on days 0, 5, and 10, and measurements were performed according to the key stability considerations. The stability considerations included properties, particle size, particle size distribution, pH value, osmotic pressure, content of the compound represented by Formula I, and content of impurities. The results are shown in Table 1 below.

[0051] [Table 7] [Table 8]

[0052] As can be seen from the experimental results in Table 1, the pharmaceutical composition provided by the present invention remains stable in pH and osmotic pressure, and there is no obvious change in related substances and contents even after being left for 10 days under 4500Lx light irradiation conditions or 60°C high temperature conditions. It has better stability under light irradiation and high temperature than the pharmaceutical composition provided by the comparative example, can be stored at room temperature, and is convenient for patients to use. At the same time, the pH and osmotic pressure of the pharmaceutical composition are close to the intraocular environment, the particle size distribution is uniform, and D 50 The particle size does not exceed 3.5 μm, which provides better comfort to the patient.

[0053] The drug composition obtained in Comparative Example 1 showed a clear change in pH value under conditions of 4500 Lx light irradiation or a high temperature of 60°C, and was therefore poorly stable. In addition, the drug composition obtained in Comparative Example 1 was a gel, and its osmotic pressure could not be measured, and it did not meet the requirements of the intraocular environment. 50 , D 90 The particle size is large and the comfort is poor.

[0054] Treatment Efficacy Test Nine patients suffering from floaters were selected, and from the date of definitive diagnosis, the pharmaceutical composition provided in Example 1 was administered 4 times a day, 2 drops each time. The patients were re-examined on the 15th and 30th days, and the therapeutic effect of floaters on the patients was observed, which is specifically shown in Table 2 below.

[0055] [Table 9] [Table 10]

[0056] As can be seen from the therapeutic effects in Table 2, after administration for about 15 days, the pharmaceutical composition provided by the present invention can significantly shallow and / or reduce the black spots and bands in front of the eyes and improve contrast sensitivity; after administration for about 30 days, the black spots and bands in front of the eyes can be almost eliminated or even completely eliminated, visual quality such as contrast sensitivity can be significantly improved, floaters can be basically cured, and there are no other side effects.

[0057] Although the present invention has been described in detail above using general descriptions, specific embodiments and tests, some modifications or improvements can be made based on the present invention, which are obvious to those skilled in the art. Therefore, any modifications or improvements made within the scope of the present invention fall within the scope of protection of the present invention.

Claims

1. A pharmaceutical composition comprising, as ingredients, a compound represented by formula I, hydroxypropyl methylcellulose, benzalkonium chloride, a pH adjuster, and a solubilizer, The pharmaceutical composition comprises, by weight, 0.01-4 parts of a compound of formula I, 2-12 parts of hydroxypropyl methylcellulose, 0.05-0.06 parts of benzalkonium chloride, 1-20 parts of a pH adjuster, and 10-50 parts of a solubilizer, and the pH of the pharmaceutical composition is 6-8; the pH adjuster is boric acid or borax; The drug composition, wherein the solubilizer is one or a combination of at least two selected from polysorbate-80, glycerin, and hydrogenated castor oil-RH40. 【Chemistry 1】

2. 2. The pharmaceutical composition according to claim 1, wherein the concentration of the compound of formula I in the pharmaceutical composition is 0.01-4 mg / mL.

3. The pharmaceutical composition of claim 2, wherein the concentration of the compound of formula I in the pharmaceutical composition is 0.1 mg / mL, 0.2 mg / mL, 0.3 mg / mL, 0.4 mg / mL, 0.5 mg / mL, 1 mg / mL, 2 mg / mL, 3 mg / mL or 4 mg / mL.

4. The pharmaceutical composition comprises, as ingredients, in parts by weight: 2 parts of the compound of formula I, 6 parts of hydroxypropyl methylcellulose, 16.5 parts of boric acid, 2 parts of borax, and 0.05 parts of benzalkonium chloride, Or 2 parts of the compound of formula I, 6 parts of hydroxypropyl methylcellulose, 40 parts of polysorbate-80, 16 parts of boric acid, 1.6 parts of borax, and 0.05 parts of benzalkonium chloride, Or the pharmaceutical composition according to claim 1, comprising 2 parts of the compound of formula I, 6 parts of hydroxypropyl methylcellulose, 10 parts of hydrogenated castor oil-RH40, 17 parts of boric acid, 1.7 parts of borax, and 0.05 parts of benzalkonium chloride.

5. The components, in parts by weight, are: 2 parts of the compound of formula I, 6 parts of hydroxypropyl methylcellulose, 25 parts of glycerin, and 0.05 parts of benzalkonium chloride; Or a pharmaceutical composition comprising 2 parts of the compound of formula I, 6 parts of hydroxypropyl methylcellulose, 10 parts of hydrogenated castor oil-RH40, 40 parts of polysorbate-80, 25 parts of glycerin, and 0.05 parts of benzalkonium chloride. 【Chemistry 2】

6. 6. The pharmaceutical composition of claim 5, wherein the particle size of the compound of formula I is <90 μm.

7. 7. The pharmaceutical composition of claim 6, wherein the particle size of the compound of formula I is ≦50 μm.

8. 8. The pharmaceutical composition according to claim 7, characterized in that the particle size distribution of the compound of formula I is D90≦7 μm and / or D50≦4 μm.

9. The pharmaceutical composition according to claim 5, wherein the pharmaceutical composition is in the form of a suspension, emulsion or gel, preferably an emulsion.

10. A method for preparing the pharmaceutical composition according to any one of claims 1 to 9, comprising uniformly mixing a compound represented by formula I, hydroxypropyl methylcellulose, benzalkonium chloride, a pH adjuster, and a solubilizing agent in prescribed amounts to obtain the pharmaceutical composition.

11. The preparation method comprises: Step (1) of dissolving hydroxypropyl methylcellulose in water for injection to obtain solution I; Step (2) dissolving hydroxypropylmethylcellulose and ingredients other than the compound of formula I in water for injection in the prescribed amounts, and then adding the solution to solution I and mixing uniformly to obtain solution II; Step (3) adding a prescribed amount of the compound represented by formula I to the solution II and mixing uniformly to obtain solution III; 11. The method of claim 10, further comprising the step (4) of making up the solution III to volume with water for injection to obtain the drug composition.

12. A pharmaceutical composition according to any one of claims 1 to 9 for preventing or treating cataracts or floaters.

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