Ophthalmic composition comprising brimonidine

Abstract

The present invention relates to an ophthalmic composition comprising brimonidine or a salt thereof, a citrate or a hydrate thereof, and trometamol, and having excellent stability and therapeutic effects.

Description

[0001] Description of the Invention

[0002]

Title of invention

[0003]

Technical Field

[0004]

Background Art

[0005]

Prior Art Documents

[0006]

Patent Document

[0007] (Patent Document 1) Republic of Korea Patent Publication No. 10-2003-0017500

[0008]

Contents of the invention

[0009] [Technical Problem] The present invention provides an ophthalmic composition comprising brimonidine or a salt thereof, which comprises stably dissolved brimonidine, can be safely administered to the eye, has a small amount of generated flexible substances during storage, and can maintain a stable state without precipitation or change in properties.

[0010]

Technical Solution

[0011] 0.2 to 5 w / v%, 0.2 to 1 w / v%, 0.3 to 1 w / v%, 0.4 to 1 w / v%, 0.2 to

[0012] It may be included at 0.5 w / v%, 0.3 to 0.5 w / v% or 0.3 to 0.4 w / v%. In one embodiment, the ophthalmic composition may include brimonidine or a salt thereof at 0.2 w / v% or more based on the total volume of the ophthalmic composition. For example, brimonidine or a salt thereof may be included at 0.2 to 1 w / v%, 0.3 to 1 w / v%, 0.2 to 0.5 w / v%. In one embodiment, the ophthalmic composition may include brimonidine or a salt thereof at 0.3 w / v% or more and 0.5 w / v% or less based on the total volume of the ophthalmic composition. For example, brimonidine or a salt thereof may be included at 0.3 to 0.5 w / v% or 0.3 to 0.4 w / v%. In embodiments of the present invention, the ophthalmic composition according to the present invention may include 0.3 w / v% or more of brimonidine or a salt thereof; citrate or a hydrate thereof; and tromethamine, based on the total volume of the ophthalmic composition. In embodiments of the present invention, the citrate or a hydrate thereof may be sodium citrate or a hydrate thereof. The citrate or a hydrate thereof in the present invention may be a stabilizer that can minimize the generation of flexible substances in the ophthalmic composition. Specifically, in embodiments of the present invention, the ophthalmic composition may include sodium citrate hydrate. In embodiments of the present invention, the ophthalmic composition may include sodium citrate dihydrate (H0C(C00Na)(CH2C00Na)2 • 2H2O). In embodiments of the present invention, the ophthalmic composition may include citrate or a hydrate thereof at 0.01 w / v% or more, 0.1 w / v% or more based on the total volume of the ophthalmic composition, and 10 w / v% or less, 6 w / v% or less, 3 w / v% or less, 1 w / v% or less, 0.8 w / v% or less, 0.It may contain 6 w / v% or less. For example, the ophthalmic composition may contain 0.01 to 10 w / v%, 0.01 to 6 w / v%, 0.01 to 3 w / v%, 0.1 to.

[0013] It can be included in an amount of 3 w / v%, 0.1 to 1 w / v%, 0.1 to 0.6 w / v%, 0.01 to 1 w / v%, 0.01 to 0.8 w / v%, or 0.01 to 0.6 w / v%. In embodiments of the present invention, trometamol is a compound whose IUPAC name is 2-amino-2-(hydroxymethyl)propane-1,3-diol. Trometamol in the present invention can adjust the pH of the ophthalmic composition to be greater than 7, 7.2 or higher, or 7.4 or higher. In embodiments of the present invention, the ophthalmic composition may contain trometamol in an amount of 0.01 w / v% or more, 0.1 w / v% or more, and 10 w / v% or less, 6 w / v% or less, 3 w / v% or less, 1 w / v% or less, 0.8 w / v% or less, or 0.6 w / v% or less, based on the total volume of the ophthalmic composition. For example, the ophthalmic composition can contain citrate in an amount of 0.01 to 10 w / v%, 0.01 to 6 w / v%, 0.01 to 3 w / v%, 0.1 to 3 w / v%, 0.1 to 1 w / v%, 0.1 to 0.6 w / v%, 0.01 to 1 w / v%, 0.01 to 0.8 w / v%, or 0.01 to 0.6 w / v%. In embodiments of the present invention, the pH of the ophthalmic composition can be 7.2 or more, 7.3 or more, or 7.4 or more, and 9 or less, or 8 or less. For example, the pH of the ophthalmic composition can be 7.2 to 9, 7.2 to 8, 7.3 to 8, or 7.4 to 8. In embodiments of the present invention, the ophthalmic composition according to the present invention may include brimonidine or a salt thereof; citrate or a hydrate thereof; and trometamol in an amount of 0.2 w / v% or more based on the total volume of the ophthalmic composition, and may have a pH of 7.2 or more.The ophthalmic composition of the present invention comprises citrate or a hydrate thereof and trometamol together with brimonidine or a salt thereof, thereby maintaining a transparent state while having a pH of more than 7, reducing the generation of volatile substances, and stably storing the composition so as to maintain an osmotic pressure range similar to that of tears. In embodiments of the present invention, the ophthalmic composition may comprise sulfobutyl ether-p-cyclodextrin (SBE-p-CD) or a salt thereof. In embodiments of the present invention, the salt of SBE-p-CD may include, but is not particularly limited to, a metal salt. For example, the salt of SBE-p-CD may be a sodium salt. In embodiments of the present invention, the ophthalmic composition may contain SBE-P-CD or a salt thereof in an amount of 1 w / v% or more, 3 w / v% or more, 4 w / v% or more, 5 w / v% or more, or 6 w / v% or more, and may contain 15 w / v% or less, 10 w / v% or less, or 8 w / v%. For example, the ophthalmic composition may contain SBE-P-CD or a salt thereof in an amount of 1 to 15 w / v%, 1 to 10 w / v%, 3 to 10 w / v%, 4 to 10 w / v%, 5 to 10 w / v%, 4 to 8 w / v%, or 5 to 8 w / v%. In embodiments of the present invention, the ophthalmic composition may contain xanthan gum. In embodiments of the present invention, the ophthalmic composition may contain xanthan gum in an amount of 0.01 w / v% or more, 0.1 w / v% or more, 10 w / v% or less, 6 w / v% or less, 3 w / v% or less, 1 w / v% or less, 0.8% or less, or 0.6 w / v% or less. For example, the ophthalmic composition may contain xanthan gum in an amount of 0.01 to 10 w / v%, 0.01 to 6 w / v%, 0.01 to 0.6 w / v%, 0.1 to 3 w / v%, 0.1 to 1 w / v%, 0.1 to 0.6 w / v%, or 0.01 to 1 w / v%.According to the ophthalmic composition of the present invention, by additionally including at least one of SBE-p-CD or a salt thereof and xanthan gum in addition to brimonidine or a salt thereof, citrate or a hydrate thereof and trometamol, brimonidine or a salt thereof can be stably and sufficiently dissolved during the manufacturing process, and a stable state can be maintained without occurrence of precipitation and changes in properties, pH, osmotic pressure, etc. during storage. In embodiments of the present invention, the ophthalmic composition may include brimonidine or a salt thereof; citrate or a hydrate thereof; trometamol; and SBE-p-CD. At this time, the brimonidine or a salt thereof may be 0.2 w / v% or more with respect to the total volume of the ophthalmic composition, and the pH of the ophthalmic composition may be 7.2 or more. In embodiments of the present invention, the ophthalmic composition may include brimonidine or a salt thereof; citrate or a hydrate thereof; trometamol, and xanthan gum. At this time, brimonidine or a salt thereof may be 0.2 w / v% or more based on the total volume of the ophthalmic composition, and the pH of the ophthalmic composition may be 7.2 or more. In embodiments of the present invention, the ophthalmic composition may include brimonidine or a salt thereof; a citrate or a hydrate thereof; trometamol; SBE-P-CD or a salt thereof; and xanthan gum. At this time, the brimonidine or a salt thereof may be 0.2 w / v% or more based on the total volume of the ophthalmic composition, and the pH of the ophthalmic composition may be 7.2 or more. In embodiments of the present invention, the ophthalmic composition may include 0.3 w / v% or more of brimonidine or a salt thereof; a citrate or a hydrate thereof; and trometamol. At this time, the ophthalmic composition may include SBE-P-CD or a salt thereof; and / or xanthan gum, and the pH of the ophthalmic composition may be 7.2 or more. In embodiments of the present invention, the ophthalmic composition has an amount of 0.3 to 0.A composition comprising: 4 w / v% brimonidine or a salt thereof; citrate or a hydrate thereof; and trometamol, and may have a pH of 7.2 or higher. In this case, the ophthalmic composition may comprise SBE-P-CD or a salt thereof; and / or xanthan gum. In embodiments of the present invention, the ophthalmic composition comprises: 0.2 w / v% or more brimonidine or a salt thereof; citrate or a hydrate thereof; trometamol; SBE-P-CD or a salt thereof; and xanthan gum, and may have a pH of 7.2 or higher, for example, 7.2 to 8. In embodiments of the present invention, the ophthalmic composition comprises: 0.3 w / v% or more brimonidine or a salt thereof; citrate or a hydrate thereof; trometamol; and SBE-p-.

[0014] CD or a salt thereof; and xanthan gum, and may have a pH of 7.4 or higher, for example,

[0015] 7.4 to 8. In embodiments of the present invention, the ophthalmic composition may comprise 0.2 to 0.5 w / v% of brimonidine or a salt thereof; 0.01 w / v% to 1 w / v% of a citrate or a hydrate thereof; and 0.01 w / v% to 1 w / v% of trometamol. At this time, the pH of the ophthalmic composition may be 7.2 to 8. In embodiments of the present invention, the ophthalmic composition may comprise 0.2 to 1 w / v% of brimonidine or a salt thereof; 0.01 w / v% to 1 w / v% of a citrate or a hydrate thereof; and 0.01 w / v% to 1 w / v% of trometamol; 1 to 10 w / v% of SBE-p-CD or a salt thereof; And 0.1 to 0.6 w / v% of xanthan gum. At this time, the pH of the ophthalmic composition may be 7.2 or higher, for example, pH 7.2 to 8. In embodiments of the present invention, the ophthalmic composition may include 0.3 to 0.4 w / v% of brimonidine or a salt thereof; 0.01 to 1 w / v% of citrate or a hydrate thereof; and 0.01 to 1 w / v% of trometamol; 1 to 10 w / v% of SBE-p-CD or a salt thereof; and 0.1 to 0.6 w / v% of xanthan gum. At this time, the pH of the ophthalmic composition may be 7.2 or higher, for example, pH 7.2 to 8. In embodiments of the present invention, the ophthalmic composition may comprise 0.2 w / v% of brimonidine or a salt thereof; citrate or a hydrate thereof; and trometamol, may not comprise sodium hydroxide and hydrochloric acid, and may have a pH of 7.2 or higher. In embodiments of the present invention, the ophthalmic composition may comprise 0.3 to 0.4 w / v% of brimonidine or a salt thereof; citrate or a hydrate thereof; and trometamol, may not comprise sodium hydroxide and hydrochloric acid, and may have a pH of 7.2 or higher, for example, 7.2 to 8.In embodiments of the present invention, the ophthalmic composition may include additives such as a buffer, a solubilizer, a release agent, a thickener, and an isotonic agent. In embodiments of the present invention, the buffer may include one or more of acetic acid, phosphoric acid, boric acid, a salt thereof, and / or a hydrate or anhydride thereof, but is not limited thereto. The buffer may be added in an appropriate amount to maintain an appropriate pH. In embodiments of the present invention, the ophthalmic composition may include polysorbate 20, polysorbate 80, and the like as a solubilizer. In embodiments of the present invention, the ophthalmic composition may include polyvinylpyrrolidone, a cellulose-based compound, and the like as a thickener. The ophthalmic composition of the present invention may be a solution containing water. In the present invention, the "solution" may not include a suspension. In the present invention, the "solution" may not include an emulsion. The ophthalmic composition of the present invention may not be a suspension. The ophthalmic composition of the present invention may not be an emulsion. The ophthalmic composition of the present invention may be a solution having a transparent state containing water. In embodiments of the present invention, the water used as an aqueous medium may be sterile purified water, water for injection, etc. suitable for the manufacture of ophthalmic preparations. In one embodiment, the ophthalmic composition of the present invention may be an aqueous ophthalmic composition containing water. In one embodiment of the present invention, (1) the ophthalmic composition of the present invention comprises 0.2 w / v% or more of brimonidine or a salt thereof; citrate or a hydrate thereof; and trometamol, and has a pH of 7.2 or more.

[0016] (2) In the ophthalmic composition of (1), the citrate is sodium citrate.

[0017] (3) In the ophthalmic composition of (1) or (2), brimonidine or a salt thereof is 0.2 to 0.5 w / v%.

[0018] (4) In any one of the ophthalmic compositions (1) to (3) above, the pH is 7.2 to 8.

[0019] (5) In any one of the ophthalmic compositions (1) to (4), the ophthalmic composition comprises sulfobutyl ether-p-cyclodextrin (SBE-p-CD) or a salt thereof; and xanthan gum.

[0020] (6) In the ophthalmic composition of (5) above, SBE-P-CD or its salt is 1 to

[0021] It contains 15 w / v%, and xanthan gum contains 0.01 to 1 w / v%.

[0022] (7) In any one of the ophthalmic compositions (1) to (6), the ophthalmic composition is a transparent solution containing water.

[0023] (8) In any one of the ophthalmic compositions (1) to (7), the ophthalmic composition comprises at least one selected from a buffer, a solubilizer, a release agent, and a thickener.

[0024] Contains one or more additives.

[0025] (9) In any one of the ophthalmic compositions (1) to (8) above, the ophthalmic composition does not contain sodium hydroxide and hydrochloric acid, and has a pH of 7.2 to 8.

[0026] (10) In any one of the ophthalmic compositions (1) to (9), the ophthalmic composition is for the prevention, improvement, or treatment of glaucoma and / or intraocular hypertension. In embodiments of the present invention, the method for the prevention, improvement, or treatment of glaucoma and / or intraocular hypertension of the present invention comprises administering the ophthalmic composition of any one of the above (1) to (9) to a subject in need thereof. In one embodiment of the present invention, the present invention is a use of the ophthalmic composition of any one of the above (1) to (9) for the prevention, improvement, or treatment of glaucoma and / or intraocular hypertension. In one embodiment of the present invention, the present invention is a use of the ophthalmic composition of any one of the above (1) to (9) for the manufacture of a medicament for the prevention, improvement, or treatment of glaucoma and / or intraocular hypertension. In embodiments of the present invention, the osmolality of the ophthalmic composition may be 250 to 400 mOsmol / kg. For example, the osmotic pressure of the ophthalmic composition of the present invention may be 270 to 330 mOsmol / kg. In embodiments of the present invention, the ophthalmic composition, when stored at a temperature of 70°C, produces less than 0.1% of individual unknown impurities for 7 days.

[0027] It may be 0.05% or less. In embodiments of the present invention, when the ophthalmic composition is stored at a temperature of 70°C, the amount of each unidentified flexible substance may be reduced by 5% or more, 10% or more, 20% or more, 30% or more, 40% or more, or 50% or more. In embodiments of the present invention, the ophthalmic composition may be a solution that remains transparent and stable for at least 3 months when stored at a temperature of 20°C to 40°C. In embodiments of the present invention, the ophthalmic composition may be a solution that remains transparent and stable for at least 2 weeks when stored at a temperature of 70°C. In embodiments of the present invention, the ophthalmic composition comprises brimonidine or a salt thereof as an active ingredient, and may exhibit pharmacological activity exhibited by brimonidine or a salt thereof. Specifically, the ophthalmic composition may be useful for preventing, improving, or treating glaucoma and / or intraocular hypertension. In embodiments of the present invention, the ophthalmic composition may further comprise an additional effective ingredient in addition to brimonidine or a salt thereof. Examples of the additional active ingredient include latanoprost, bimatoprost, travoprost, taf luprost, netarsudi 1, carteolol, timoptic, timolol, betaloxol, levobunolol, metipranolol, brinzolamide, dorzolamide, acetazolamide, methazolamide, or a pharmaceutically acceptable salt thereof, each of which may be used alone or in combination of two or more thereof with brimonidine or a salt thereof.In embodiments of the present invention, the ophthalmic composition may be disposable or multi-use, and specifically, may be disposable. When the ophthalmic composition is multi-use, the composition may further include a preservative. The preservative may be a quaternary ammonium compound such as benzalkonium chloride, polyquaternium-1 (e.g., polyquad); a guanidine compound such as chlorhexidine; chlorobutanol; a mercury preservative; or the like. In embodiments of the present invention, the ophthalmic composition may be administered once to three times a day. For example, the ophthalmic composition may be administered once, twice, or three times a day. The ophthalmic composition of the present invention may be provided as a transparent aqueous solution by including stably dissolved brimonidine. In addition, the ophthalmic composition of the present invention may maintain a stable state without precipitation occurring during storage and without a change in properties such as color. In addition, the ophthalmic composition has excellent stability in that the content of the active ingredient, pH, and other physicochemical properties are well maintained, and the generation of soluble substances is low. Therefore, the ophthalmic composition of the present invention can maintain a stable state for a long period of time, can be safely administered to the eye, and can exhibit excellent therapeutic effects without side effects. The method for preparing the ophthalmic composition according to the present invention includes a step of preparing a mixed solution comprising brimonidine or a salt thereof, a citrate or a hydrate thereof, and trometamol. In embodiments of the present invention, the step of preparing the mixed solution may include a step of preparing a first solution comprising brimonidine or a salt thereof, a citrate or a hydrate thereof, and water; a step of preparing a second solution comprising trometamol and water; and a step of mixing the first and second solutions. In the step of preparing the mixed solution, the citrate or a hydrate thereof may be included in the second solution.In the step of preparing the mixed solution, a part of the total trometamol content included in the ophthalmic composition according to the present invention may be included in the step of preparing the first solution. In embodiments of the present invention, the mixed solution may be a solution that has undergone a sterilization process. In one embodiment, the mixed solution may be prepared by mixing the first solution and the second solution after the sterilization process has been performed on them. In embodiments of the present invention, the first solution, the second solution, and the mixed solution in the step of preparing the mixed solution may each independently further include SBE-p-CD or a salt thereof and / or xanthan gum. In embodiments of the present invention, the first solution, the second solution, and the mixed solution in the step of preparing the mixed solution may each independently further include additives such as a buffer, a pH adjuster, a solubilizer, a sustained-release agent, a thickener, and an isotonic agent. In embodiments of the present invention, the step of preparing the mixed solution may further include a step of mixing an additional active ingredient other than brimonidine or a salt thereof. The method for preparing an ophthalmic composition according to the present invention may include a step of adding a pH adjuster in the step of preparing the first solution, and / or a step of adding a pH adjuster to the mixed solution. At this time, the pH adjuster may be hydrochloric acid or sodium hydroxide. For example, in embodiments of the present invention, in the step of preparing the first solution, hydrochloric acid may be added so that brimonidine can be dissolved, and / or in the step of preparing the mixed solution, hydrochloric acid or sodium hydroxide may be added after mixing the first solution and the second solution. The ophthalmic composition of the present invention is for preventing, improving, or treating glaucoma and / or ocular hypertension. The present invention provides a method for preventing, improving, or treating glaucoma and / or ocular hypertension, comprising administering an effective amount of the ophthalmic composition of the present invention to a subject in need thereof.The present invention provides a use of the ophthalmic composition of the present invention for preventing, improving or treating glaucoma and / or intraocular hypertension. The present invention provides a use of the ophthalmic composition of the present invention for manufacturing a medicament for preventing, improving or treating glaucoma and / or intraocular hypertension. In the method for manufacturing an ophthalmic composition according to the present invention, brimonidine or a salt thereof, citrate or a hydrate thereof and trometamol, and SBE- P -CD or a salt thereof and xanthan gum, and further additional additives and additional active ingredients are substantially the same as those described above, and thus redundant detailed descriptions are omitted.

[0028] [Effect of the invention] The ophthalmic composition of the present invention can be provided as a transparent aqueous solution by including stably dissolved brimonidine. In addition, the ophthalmic composition of the present invention can maintain a stable state without precipitation occurring during storage and without changes in properties such as color. In addition, the ophthalmic composition has excellent stability in that the content of the active ingredient, pH, osmotic pressure, and other physicochemical properties are well maintained, and the generation of related substances is low. Therefore, the ophthalmic composition of the present invention can be safely administered to the eye for a long period of time and can maintain a stable state, thereby exhibiting excellent therapeutic effects without side effects.

[0029]

Brief description of the drawing

[0030]

Form for carrying out the invention

[0031] [Table 1] Experimental Example 1: Stability Evaluation 1 - Appearance and pH Compositions 1 to 4 were all prepared as transparent solutions. Additionally, each of Compositions 1 to 4 was stored at 70°C for 10 days, and the pH change from day 0 to day 10 was measured. As a result, it was confirmed that Composition 1 maintained a transparent appearance without precipitation, and the pH on day 10 was 7.5, indicating that there was practically no pH change. On the other hand, it was confirmed that the pH of Compositions 3 and 4 significantly changed to the range of about 7.1 to 7.2. In particular, it was confirmed that the pH of Compositions 3 and 4 rapidly changed to about 7.2 to 7.3 in only 4 days. Through this, it can be seen that the stability of the appearance and pH of Composition 1 including both citrate and trometamol of the present invention is very excellent. Experimental Example 2: Stability Evaluation 2 - Amount of Generation of Related Substances For the above compositions, 70°C was generated.After storage in In for one week, the amount of unknown impurities and total impurities generated was measured by liquid chromatography on the 4th and 7th days. As a result, it can be confirmed that Composition 1 did not generate any unknown impurities on the 4th day, and even on the 7th day, it was only about 0.1% or less, which was about 0.05% or less (see Fig. 1). On the other hand, Composition 2 generated about 0.2% of unknown impurities on the 4th day, and it can be confirmed that it increased to about 0.25% on the 7th day. In addition, it can be confirmed that the amount of total impurities generated in Composition 2 is greater than that in Composition 1 (about 16% increase). Through this, it can be seen that the composition containing both citrate and trometamol of the present invention has excellent stability because it generates little impurities. Manufacturing Example 2: Manufacturing of ophthalmic compositions 5 to 7 Compositions 5 to 7 were manufactured according to the ingredients and contents described in Table 2 below in the same manner as the manufacturing method of Composition 1, but the pH was adjusted with sodium hydroxide or hydrochloric acid, if necessary. Specifically, when manufacturing the first solution, hydrochloric acid was further added so that brimonidine could be dissolved, or the first solution and the second solution were mixed, and then the pH was adjusted to about 7.6 using hydrochloric acid or sodium hydroxide.

[0032] [Table 2] Experimental Example 3: Stability Evaluation 3 - Appearance and pH The above compositions 5 to 7 were stored at 70°C for 14 days, and the appearance and pH were measured. As a result, it was confirmed that all compositions 5 to 7 maintained a transparent solution state and that there was no change in appearance. In addition, it was confirmed that the pH of all compositions 5 to 7 was maintained stably (see Table 3).

[0033] [Table 3] Through this, it can be seen that the composition containing citrate and trometamol of the present invention has excellent properties and pH stability. Manufacturing Example 3: Manufacturing of ophthalmic compositions 8 to 10 Compositions 8 to 10 were manufactured according to the ingredients and contents described in Table 4 below in the same manner as the manufacturing method of the above composition 1, but if necessary, the pH was adjusted with sodium hydroxide or hydrochloric acid. Specifically, when manufacturing the first solution, hydrochloric acid was further added so that brimonidine could be dissolved, or the first solution and the second solution were mixed, and then the pH was adjusted to about 7.6 using hydrochloric acid or sodium hydroxide.

[0034] [Table 4] Experimental Example 4: Stability Evaluation 4 - Main Ingredient Content and Amount of Unidentified Related Materials The compositions 8 to 10 were stored at 70°C for 14 days, and the main ingredient content and the amount of unidentified related materials were measured using liquid chromatography. As a result, it was confirmed that the content (%) of the main ingredient of all compositions 8 to 10 was stably maintained (see Table 5), and the amount of unidentified related materials generated was also very small (see Table 6). [Table 5]

[0035] [Table 6] Through this, it can be seen that the stability of the composition containing citrate and trometamol of the present invention is very excellent. While specific parts of the present invention have been described in detail above, it will be apparent to those skilled in the art that such specific descriptions are merely preferred embodiments and that the scope of the present invention is not limited thereby. Therefore, the actual scope of the present invention will be defined by the appended claims and their equivalents.

Claims

【Scope of Claims】 Claim 11 An ophthalmic composition comprising brimonidine or a salt thereof in an amount of 0.2 w / v% or more; a citrate or a hydrate thereof; and trometamol, and having a pH of 7.2 or more. 【

2. An ophthalmic composition according to claim 1, wherein the citrate is sodium citrate. 【

3. An ophthalmic composition according to claim 1, wherein brimonidine or a salt thereof is present in an amount of 0.2 to 0.5 w / v%. 【

4. An ophthalmic composition according to claim 1, wherein the pH is 7.2 to 8. 【

5. An ophthalmic composition according to claim 1, wherein the ophthalmic composition comprises sulfobutyl ether-p-cyclodextrin (SBE-p-CD) or a salt thereof; and xanthan gum. 【

6. In claim 5, SBE-p-CD or a salt thereof is contained in an amount of 1 to 15 w / v%, An ophthalmic composition comprising xanthan gum in an amount of 0.01 to 1 w / v%. 【

7. An ophthalmic composition according to claim 1, wherein the ophthalmic composition is a transparent solution containing water. 【

8. An ophthalmic composition according to claim 1, wherein the ophthalmic composition comprises at least one additive selected from a buffer, a solubilizer, a release-promoting agent, and a thickening agent. 【

9. An ophthalmic composition according to claim 1, wherein the ophthalmic composition does not contain sodium hydroxide and hydrochloric acid and has a pH of 7.2 to 8.

10. An ophthalmic composition according to any one of claims 1 to 9, wherein the ophthalmic composition is for the prevention, improvement, or treatment of glaucoma and / or intraocular hypertension.

11. An ophthalmic composition according to any one of claims 1 to 9, which requires the same. A method for preventing, improving, or treating glaucoma and / or ocular hypertension, comprising administering to a subject.

12. Use of the ophthalmic composition of any one of claims 1 to 9 for the prevention, improvement, or treatment of glaucoma and / or intraocular hypertension.

13. Use of the ophthalmic composition of any one of claims 1 to 9 for the manufacture of a medicament for preventing, improving, or treating glaucoma and / or intraocular hypertension.

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