Eye drop aqueous pharmaceutical composition containing emedastine fumarate and preparation method thereof

Abstract

According to the emedastine fumarate-containing eye drop aqueous pharmaceutical composition and the preparation method thereof provided by the invention, a bacteriostatic agent and a chelating agent EDTA are not contained in a formula, boric acid and borax are used as buffering agents, and the composition has antiseptic and antibacterial effects, so that the damage to eyes caused by using a bacteriostatic agent represented by benzalkonium chloride is avoided to a great extent; the obtained eye drop aqueous pharmaceutical composition is higher in safety, stronger in buffering capacity, smaller in irritation, fewer in impurities and higher in stability. The preparation method provided by the invention is simple and easy to operate, the production cost is greatly saved, the dissolution of the raw material medicines is greatly accelerated, and the obtained liquid medicine is more uniform.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical preparation technology, specifically relating to an aqueous eye drop composition containing emestin fumarate, and a method for preparing the aqueous eye drop composition. Background Technology

[0002] Emestin is a relatively selective histamine H1 receptor antagonist. Emestin fumarate eye drops are used to temporarily relieve the signs and symptoms of allergic conjunctivitis.

[0003] Traditional eye drops are packaged in multiple doses, which can be used repeatedly after opening. However, this repeated use can lead to microbial contamination. Therefore, most multi-dose eye drops contain antibacterial agents to prevent microbial contamination during production, storage, and use. Currently, antibacterial agents, such as benzalkonium chloride, are widely used in eye drops. The side effects of benzalkonium chloride on the eyes have been confirmed in relevant studies. Research has found that using 0.02% and 0.1% concentrations of the antibacterial agent benzalkonium chloride in eye drops severely impairs the mitochondrial oxidative function of anterior visual tissues (cornea and conjunctiva). Benzalkonium chloride shows a significant dose-dependent inhibitory effect on mitochondrial inner membrane enzymes; using higher concentrations of benzalkonium chloride reduced enzyme activity in the cornea and conjunctiva by 39.6% and 46.5%, respectively. Furthermore, studies have found that eye washes containing benzalkonium chloride are associated with corneal epithelial disorders and collapse of the corneal mucin layer.

[0004] The current formulation of multidose emesitin fumarate eye drops, as disclosed in US Patent 5441958, consists of: emesitin fumarate, benzalkonium chloride, EDTA, tromethorphan, sodium chloride, hydroxypropyl methylcellulose, sodium hydroxide and / or hydrochloric acid, and water for injection. The formulation uses 0.01% of the prescribed amount of the antibacterial agent benzalkonium chloride, and also uses 0.01% of the prescribed amount of the EDTA chelating agent. Studies have found that EDTA has a strong chelating ability and can form stable chelates with various metal ions such as calcium and iron, causing them to be excreted from the body and leading to trace element deficiency. Long-term use of preparations containing EDTA may cause kidney poisoning.

[0005] Chinese patent CN120131543A discloses a single-dose emesostine fumarate eye drop and its preparation method. The disclosed formulation consists of: emesostine fumarate, tromethamine, sodium chloride, hydroxypropyl methylcellulose, hydrochloric acid and / or sodium hydroxide solution, and water for injection. Similar to multi-dose emesostine fumarate eye drops, tromethamine is used as the buffer. Tromethamine has a relatively weak buffering capacity, and insufficient buffering capacity may increase the probability of sample changes over time and with the environment. Studies have found that high-dose or long-term use of drugs containing tromethamine may have some impact on kidney function, especially in patients with renal insufficiency. For example, ketorolac tromethamine is contraindicated in patients with renal impairment and renal failure caused by hypovolemia. It may also inhibit platelet function, increasing the risk of bleeding. Therefore, patients with bleeding tendencies or those taking anticoagulants should use it with caution. In addition, the preparation method of emestin fumarate eye drops in this patent selects high temperature to dissolve the osmotic pressure regulator and buffer. Although this can shorten the dissolution time of the osmotic pressure regulator, the continuous high temperature heating time in the liquid preparation tank is extended, which increases the production cost. Furthermore, the stirring of hydroxypropyl methylcellulose easily generates a large number of bubbles. These bubbles float on the water surface and interfere with the feeding of raw materials and other excipients, resulting in poor dissolution of raw materials and excipients.

[0006] Therefore, it is essential to develop a pharmaceutical composition and its preparation method that has few toxic side effects, strong buffering capacity, high stability, and is simple to prepare and has low production cost. Summary of the Invention

[0007] The purpose of this invention is to provide an aqueous eye drop composition containing emestin fumarate, based on existing technology. This composition does not contain antibacterial agents or the chelating agent EDTA, and uses boric acid and borax as buffers, providing antiseptic and antibacterial effects. This greatly avoids the damage to the eyes caused by antibacterial agents such as benzalkonium chloride. The resulting aqueous eye drop composition is safer, has stronger buffering capacity, less irritation, fewer impurities, and higher stability.

[0008] Another objective of this invention is to provide a method for preparing the above-mentioned aqueous eye drop pharmaceutical composition containing emestin fumarate, which is simple and easy to operate, significantly reduces production costs, greatly accelerates the dissolution of the active pharmaceutical ingredient, and results in a more uniform solution.

[0009] The technical solution of the present invention is as follows:

[0010] An aqueous eye drop composition containing emesitine fumarate is prepared by dissolving the active ingredient emesitine fumarate, a thickener, an osmotic pressure regulator, a buffer, a pH adjuster, and water for injection into a solution, which is then degassed under vacuum, sterilized by filtration, and filled into a container. During the preparation of the solution, the pH value is adjusted to 7.0-7.8 using a pH adjuster.

[0011] The thickener is hydroxypropyl methylcellulose, preferably hydroxypropyl methylcellulose 2910-E4M; the osmotic pressure regulator is sodium chloride; the buffer is boric acid and borax; and the pH regulator is hydrochloric acid solution.

[0012] In this invention, during the preparation of the medicinal solution, the pH value is adjusted to 7.0-7.8 using a pH adjuster; preferably, the pH value is adjusted to 7.3-7.5 using a pH adjuster; more preferably, the pH value is adjusted to 7.4 using a pH adjuster.

[0013] The pH adjuster is a hydrochloric acid solution, for example, a 0.5-1.5 mol / L hydrochloric acid solution, preferably a 1.0 mol / L hydrochloric acid solution.

[0014] In a preferred embodiment, the aqueous eye drop composition containing emeslin fumarate provided by the present invention has the following concentrations: emeslin fumarate: 0.8-1.0 mg / ml; hydroxypropyl methylcellulose 2910-E4M: 1.0-4.0 mg / ml; sodium chloride: 6.0-8.0 mg / ml; boric acid: 3.0-6.0 mg / ml; borax: 3.5-6.5 mg / ml.

[0015] In a more preferred embodiment, the aqueous eye drop composition containing emeslin fumarate provided by the present invention has the following mass concentrations: emeslin fumarate 0.83-0.93 mg / ml; hydroxypropyl methylcellulose 2910-E4M 1.5-3.5 mg / ml; sodium chloride 6.5-7.5 mg / ml; boric acid 3.5-5.5 mg / ml; and borax 4.0-6.0 mg / ml.

[0016] In a particularly preferred embodiment, the aqueous eye drop composition containing emeslin fumarate provided by the present invention has the following mass concentrations: emeslin fumarate 0.855-0.905 mg / ml; hydroxypropyl methylcellulose 2910-E4M 2.0-3.0 mg / ml; sodium chloride 6.8-7.2 mg / ml; boric acid 4.0-5.0 mg / ml; and borax 4.5-5.5 mg / ml.

[0017] For example, in the aqueous eye drop composition containing emesitin fumarate provided by the present invention, the mass concentration of emesitin fumarate is 0.855 mg / ml; the mass concentration of hydroxypropyl methylcellulose 2910-E4M is 2.0 mg / ml; the mass concentration of sodium chloride is 6.8 mg / ml; the mass concentration of boric acid is 4.0 mg / ml; and the mass concentration of borax is 4.5 mg / ml.

[0018] For example, in the aqueous eye drop composition containing emesitin fumarate provided by the present invention, the mass concentration of emesitin fumarate is 0.884 mg / ml; the mass concentration of hydroxypropyl methylcellulose 2910-E4M is 2.5 mg / ml; the mass concentration of sodium chloride is 7.0 mg / ml; the mass concentration of boric acid is 4.5 mg / ml; and the mass concentration of borax is 5.0 mg / ml.

[0019] For example, in the aqueous eye drop composition containing emesitin fumarate provided by the present invention, the mass concentration of emesitin fumarate is 0.905 mg / ml; the mass concentration of hydroxypropyl methylcellulose 2910-E4M is 3.0 mg / ml; the mass concentration of sodium chloride is 7.2 mg / ml; the mass concentration of boric acid is 5.0 mg / ml; and the mass concentration of borax is 5.5 mg / ml.

[0020] The present invention also provides a method for preparing the above-mentioned aqueous eye drop pharmaceutical composition containing emestin fumarate, comprising the following steps:

[0021] (1) Under the condition of 60-90℃, the thickener is added to part of the water for injection, and after stirring and dispersing evenly, the resulting mixed solution is stirred and cooled to below 25℃ to dissolve and clarify. Osmotic pressure regulator, buffer and emestin fumarate are added to it, and stirring is continued until completely dissolved. Vacuum is turned on to remove bubbles during the preparation process.

[0022] (2) Adjust the pH of the solution obtained in step (1) to 7.0-7.8 using a pH adjuster, add the remaining water for injection to make up the volume, and stir to obtain the drug solution;

[0023] (3) After the medicine solution is prepared, it is sterilized, filtered, and filled to obtain the product.

[0024] For the purposes of this invention, in step (1), the dispersion temperature is 60-90℃, preferably 75-85℃, and more preferably 70-80℃.

[0025] In step (1), the amount of water for injection added is 80-90% of its total amount, preferably 85%.

[0026] In step (1), when degassing, the vacuum level is -0.95 bar to -0.65 bar, preferably -0.9 bar to -0.7 bar.

[0027] For the purposes of this invention, in step (2), the pH value is adjusted to 7.0-7.8 with a pH adjuster; preferably, the pH value is adjusted to 7.3-7.5 with a pH adjuster; more preferably, the pH value is adjusted to 7.4 with a pH adjuster.

[0028] In a preferred embodiment, during step (3) when filtering and sterilizing, the filter element material is polyvinylidene fluoride.

[0029] The advantages of using the technical solution of this invention are as follows:

[0030] This invention provides an aqueous eye drop composition containing emestin fumarate and its preparation method. The formulation does not contain antibacterial agents or chelating agent EDTA, and uses boric acid and borax as buffers, which have antiseptic and antibacterial effects. This greatly avoids the damage to the eyes caused by antibacterial agents such as benzalkonium chloride. The resulting aqueous eye drop composition has higher safety, stronger buffering capacity, less irritation, fewer impurities, and higher stability.

[0031] The preparation method provided by this invention is simple and easy to operate, greatly saves production costs, significantly accelerates the dissolution of the active pharmaceutical ingredient, and results in a more uniform drug solution. Detailed Implementation

[0032] The present invention can be better understood from the following embodiments. However, those skilled in the art will readily understand that the descriptions in the embodiments are for illustrative purposes only and should not, and will not, limit the invention as detailed in the claims.

[0033] Example 1

[0034] An aqueous ophthalmic pharmaceutical composition containing emesine fumarate, comprising the following components by weight:

[0035]

[0036] The preparation method of the above-mentioned aqueous eye drop composition containing emestin fumarate includes the following steps:

[0037] (1) Add 85% of the total amount of water for injection to the mixing tank. Under the condition of 70-80℃, add the thickener (hydroxypropyl methylcellulose 2910-E4M) to the water for injection. After stirring and dispersing evenly, the resulting mixed solution is stirred and cooled to below 25℃ to obtain a clear solution. Add the osmotic pressure regulator (sodium chloride), buffer (boric acid and borax) and emestin fumarate to it. Continue stirring until completely dissolved. During the preparation process, the vacuum is continuously turned on to remove bubbles. The vacuum degree is -0.9 bar to -0.7 bar.

[0038] (2) Adjust the pH of the solution obtained in step (1) to 7.4 with 1.0 mol / L hydrochloric acid solution, add the remaining water for injection to make up the volume, and stir to obtain the drug solution;

[0039] (3) The product is sterilized by filtration using a polyvinylidene fluoride (PVDF) filter membrane, filled into low-density polyethylene pharmaceutical eye drop bottles, and packaged in a polyester / polyethylene / aluminum / polyethylene pharmaceutical composite bag.

[0040] Example 2

[0041] An aqueous ophthalmic pharmaceutical composition containing emesine fumarate, comprising the following components by weight:

[0042]

[0043] The preparation method of the above-mentioned aqueous eye drop composition containing emestin fumarate includes the following steps:

[0044] (1) Add 85% of the total amount of water for injection to the mixing tank. Under the condition of 70-80℃, add the thickener (hydroxypropyl methylcellulose 2910-E4M) to the water for injection. After stirring and dispersing evenly, the resulting mixed solution is stirred and cooled to below 25℃ to obtain a clear solution. Add the osmotic pressure regulator (sodium chloride), buffer (boric acid and borax) and emestin fumarate to it. Continue stirring until completely dissolved. During the preparation process, the vacuum is continuously turned on to remove bubbles. The vacuum degree is -0.9 bar to -0.7 bar.

[0045] (2) Adjust the pH of the solution obtained in step (1) to 7.4 with 1.0 mol / L hydrochloric acid solution, add the remaining water for injection to make up the volume, and stir to obtain the drug solution;

[0046] (3) The product is sterilized by filtration using a polyvinylidene fluoride (PVDF) filter membrane, filled into low-density polyethylene pharmaceutical eye drop bottles, and packaged in a polyester / polyethylene / aluminum / polyethylene pharmaceutical composite bag.

[0047] Example 3

[0048] An aqueous ophthalmic pharmaceutical composition containing emesine fumarate, comprising the following components by weight:

[0049]

[0050]

[0051] The preparation method of the above-mentioned aqueous eye drop composition containing emestin fumarate includes the following steps:

[0052] (1) Add 85% of the total amount of water for injection to the mixing tank. Under the condition of 70-80℃, add the thickener (hydroxypropyl methylcellulose 2910-E4M) to the water for injection. After stirring and dispersing evenly, the resulting mixed solution is stirred and cooled to below 25℃ to obtain a clear solution. Add the osmotic pressure regulator (sodium chloride), buffer (boric acid and borax) and emestin fumarate to it. Continue stirring until completely dissolved. During the preparation process, the vacuum is continuously turned on to remove bubbles. The vacuum degree is -0.9 bar to -0.7 bar.

[0053] (2) Adjust the pH of the solution obtained in step (1) to 7.4 with 1.0 mol / L hydrochloric acid solution, add the remaining water for injection to make up the volume, and stir to obtain the drug solution;

[0054] (3) The product is sterilized by filtration using a polyvinylidene fluoride (PVDF) filter membrane, filled into low-density polyethylene pharmaceutical eye drop bottles, and packaged in a polyester / polyethylene / aluminum / polyethylene pharmaceutical composite bag.

[0055] Comparative Example 1

[0056] An aqueous ophthalmic pharmaceutical composition containing emesine fumarate, comprising the following components by weight:

[0057]

[0058] The preparation method of the above-mentioned aqueous eye drop composition containing emestin fumarate includes the following steps:

[0059] (1) Add 85% of the total amount of water for injection to the mixing tank. Under the condition of 70-80℃, add the thickener (hydroxypropyl methylcellulose 2910-E4M) to the water for injection. After stirring and dispersing evenly, the resulting mixed solution is stirred and cooled to below 25℃ to obtain a clear solution. Add the osmotic pressure regulator (sodium chloride), buffer (boric acid and borax) and emestin fumarate to it. Continue stirring until completely dissolved. During the preparation process, the vacuum is continuously turned on to remove bubbles. The vacuum degree is -0.9 bar to -0.7 bar.

[0060] (2) Adjust the pH of the solution obtained in step (1) to 7.4 with 1.0 mol / L hydrochloric acid solution, add the remaining water for injection to make up the volume, and stir to obtain the drug solution;

[0061] (3) The product is sterilized by filtration using a polyvinylidene fluoride (PVDF) filter membrane, filled into low-density polyethylene pharmaceutical eye drop bottles, and packaged in a polyester / polyethylene / aluminum / polyethylene pharmaceutical composite bag.

[0062] Comparative Example 2

[0063] An aqueous ophthalmic pharmaceutical composition containing emesine fumarate, comprising the following components by weight:

[0064]

[0065] The preparation method of the above-mentioned aqueous eye drop composition containing emestin fumarate includes the following steps:

[0066] (1) Add 85% of the total amount of water for injection to the mixing tank. Under the condition of 70-80℃, add the thickener (hydroxypropyl methylcellulose 2910-E4M) to the water for injection. After stirring and dispersing evenly, the resulting mixed solution is stirred and cooled to below 25℃ to obtain a clear solution. Add the osmotic pressure regulator (sodium chloride), buffer (tromethamine) and emestin fumarate to it, and continue stirring until completely dissolved.

[0067] (2) Adjust the pH of the solution obtained in step (1) to 7.4 with 1.0 mol / L hydrochloric acid solution, add the remaining water for injection to make up the volume, and stir to obtain the drug solution;

[0068] (3) After the medicine solution is prepared, it is filtered and sterilized using a polyvinylidene fluoride (PVDF) filter membrane, filled into low-density polyethylene medicine eye drop bottles, and packaged in a polyester / polyethylene / aluminum / polyethylene medicine composite bag.

[0069] The buffering capacity of eye drop buffers is closely related to the type of buffer. The buffering capacity of eye drops is determined by testing their buffering capacity, i.e., their resistance to acid and alkali. That is, when the same volume of the drug solution is lowered or raised to a fixed pH value, the larger the volume of acid and alkali consumed, the stronger its buffering capacity, the stronger its ability to maintain osmotic pressure balance and pH stability, and the more it helps maintain the solubility and activity of the drug in the solution. Conversely, the smaller the volume of acid and alkali consumed, the weaker its buffering capacity, and the more easily the stability of the drug solution may fluctuate.

[0070] The buffer capacity of the examples and comparative examples was examined, and the results are shown in Table 1.

[0071] Table 1 Buffer Capacity Test Data

[0072]

[0073] The stability of the eye drop samples prepared by the comparative examples and comparative examples under the influencing factor test conditions and the accelerated test conditions of temperature 40℃±2℃ and humidity 25%±5%RH is shown in Table 2.

[0074] Table 2. Stability test data

[0075]

[0076]

[0077] Table 1 shows that, based on the buffer capacity test results for each group, eye drops prepared using borate buffer exhibit significantly stronger acid and alkali resistance than those prepared using tromethorphan, indicating a higher buffering capacity. Stability test data shows that eye drops prepared using borate buffer contain significantly fewer impurities. Therefore, the buffering capacity of the buffer further affects the stability of the sample, making borate buffer the preferred choice. Furthermore, borate buffer is relatively non-toxic and offers higher safety.

[0078] The eye drops are true solutions, and whether the active pharmaceutical ingredient can be completely dissolved directly affects the efficacy and safety of the drug. The dissolution of the active pharmaceutical ingredient in the examples and comparative examples was investigated, and the results are shown in Table 3.

[0079] Table 3 Results of the investigation on the dissolution of active pharmaceutical ingredients

[0080]

[0081] Conclusion: Hydroxypropyl methylcellulose easily generates bubbles when stirred. Turning on the vacuum during the solution preparation process to remove bubbles significantly accelerates the dissolution of the active pharmaceutical ingredient, resulting in rapid and uniform dissolution of the sample and a significant increase in production efficiency.

[0082] The stability of various quality properties of the emesitin fumarate eye drops sample prepared in Example 1 was further evaluated under accelerated testing at a temperature of 40℃±2℃ and a humidity of 25%±5%RH. The results are shown in Table 4.

[0083] Table 4 Accelerated Experiment Data

[0084]

[0085] Conclusion: The above data show that the eye drops prepared according to the established formula and preparation method of this product meet the standard requirements for all test items, and the sample has good stability.

[0086] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications may still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions may be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. An eye drop aqueous pharmaceutical composition containing emedastine fumarate, characterized by, is prepared by dissolving active ingredient emedastine difumarate, thickening agent, osmotic pressure regulator, buffer, pH regulator and water for injection, vacuuming to remove bubbles, filtering to remove bacteria, and filling; in the preparation of the liquid, the pH value is adjusted to 7.0-7.8 by the pH regulator, wherein the thickening agent is hydroxypropyl methyl cellulose; the osmotic pressure regulator is sodium chloride; the buffer is boric acid and borax.

2. The eye drop aqueous pharmaceutical composition containing emedastine fumarate according to claim 1, characterized by, The thickening agent is hydroxypropyl methyl cellulose 2910-E4M; the pH regulator is hydrochloric acid solution; in the preparation of the liquid, the pH value is adjusted to 7.3-7.5 by the pH regulator, preferably, in the preparation of the liquid, the pH value is adjusted to 7.4 by the pH regulator.

3. The eye drop aqueous pharmaceutical composition containing emedastine fumarate according to claim 2, characterized by, The mass concentration of emedastine difumarate in the eye drop aqueous pharmaceutical composition is 0.8-1.0 mg / ml; the mass concentration of hydroxypropyl methyl cellulose 2910-E4M is 1.0-4.0 mg / ml; the mass concentration of sodium chloride is 6.0-8.0 mg / ml; the mass concentration of boric acid is 3.0-6.0 mg / ml; and the mass concentration of borax is 3.5-6.5 mg / ml.

4. The eye drop aqueous pharmaceutical composition containing emedastine fumarate according to claim 3, characterized by, The mass concentration of emedastine difumarate in the eye drop aqueous pharmaceutical composition is 0.83-0.93 mg / ml; the mass concentration of hydroxypropyl methyl cellulose 2910-E4M is 1.5-3.5 mg / ml; the mass concentration of sodium chloride is 6.5-7.5 mg / ml; the mass concentration of boric acid is 3.5-5.5 mg / ml; and the mass concentration of borax is 4.0-6.0 mg / ml.

5. The eye drop aqueous pharmaceutical composition containing emedastine fumarate according to claim 4, characterized by, The mass concentration of emedastine difumarate in the eye drop aqueous pharmaceutical composition is 0.855-0.905 mg / ml; the mass concentration of hydroxypropyl methyl cellulose 2910-E4M is 2.0-3.0 mg / ml; the mass concentration of sodium chloride is 6.8-7.2 mg / ml; the mass concentration of boric acid is 4.0-5.0 mg / ml; and the mass concentration of borax is 4.5-5.5 mg / ml.

6. The eye drop aqueous pharmaceutical composition containing emedastine difumarate according to claim 5, wherein the mass concentration of emedastine difumarate is 0.855 mg / ml; the mass concentration of hydroxypropyl methyl cellulose 2910-E4M is 2.0 mg / ml; the mass concentration of sodium chloride is 6.8 mg / ml; the mass concentration of boric acid is 4.0 mg / ml; and the mass concentration of borax is 4.5 mg / ml. The mass concentration of emedastine difumarate in the eye drop aqueous pharmaceutical composition is 0.855 mg / ml; the mass concentration of hydroxypropyl methyl cellulose 2910-E4M is 2.0 mg / ml; the mass concentration of sodium chloride is 6.8 mg / ml; the mass concentration of boric acid is 4.0 mg / ml; and the mass concentration of borax is 4.5 mg / ml. The mass concentration of emedastine difumarate in the eye drop aqueous pharmaceutical composition is 0.884 mg / ml; the mass concentration of hydroxypropyl methyl cellulose 2910-E4M is 2.5 mg / ml; the mass concentration of sodium chloride is 7.0 mg / ml; the mass concentration of boric acid is 4.5 mg / ml; and the mass concentration of borax is 5.0 mg / ml. The mass concentration of emedastine fumarate in the eye drop aqueous pharmaceutical composition is 0.905 mg / ml; the mass concentration of hydroxypropyl methyl cellulose 2910-E4M is 3.0 mg / ml; the mass concentration of sodium chloride is 7.2 mg / ml; the mass concentration of boric acid is 5.0 mg / ml; and the mass concentration of borax is 5.5 mg / ml.

7. The method of producing the eye drop aqueous pharmaceutical composition containing emedastine fumarate according to claim 1, characterized by, The method comprises the following steps: (1) under the condition of 60-90℃, the thickening agent is added into part of the water for injection, and after stirring and uniformly dispersing, the obtained mixed solution is stirred and cooled to below 25℃ to be dissolved and clarified, the osmotic pressure regulator, the buffer and the emedastine fumarate are added into the solution, and continuous stirring is carried out until complete dissolution, and the vacuum is opened to remove bubbles during the preparation process; (2) the pH value of the solution obtained in step (1) is adjusted to 7.0-7.8 by using the pH regulator, the remaining water for injection is added to constant volume, and the liquid medicine is obtained by stirring; (3) after the preparation of the liquid medicine is completed, sterilization filtration is carried out, and then the liquid medicine is filled, and the eye drop aqueous pharmaceutical composition is obtained.

8. The method of preparing an eye drop aqueous pharmaceutical composition containing emedastine fumarate according to claim 7, characterized by, In step (1), the dispersion temperature is 75-85℃, and preferably 70-80℃; the amount of the water for injection added is 80-90% of the total amount, and preferably 85%; when the vacuum is used to remove bubbles, the vacuum degree is-0.95 bar to-0.65 bar, and preferably-0.9 bar to-0.7 bar.

9. The method of preparing an eye drop aqueous pharmaceutical composition containing emedastine fumarate according to claim 7, characterized by, In step (2), the pH value is adjusted to 7.3-7.5 by using the pH regulator; and preferably, the pH value is adjusted to 7.4 by using the pH regulator.

10. The method of preparing an eye drop aqueous pharmaceutical composition containing emedastine fumarate according to claim 7, characterized by, In step (3), when the sterilization filtration is carried out, the filter core material is polyvinylidene fluoride.

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