Aqueous liquid preparation

Abstract

To provide a technique that enables suppression of viscosity decrease over time in an aqueous liquid preparation including a water-soluble polymer.SOLUTION: An aqueous liquid preparation comprising a water-soluble polymer, the aqueous liquid preparation being contained in a resin container sterilized with hydrogen peroxide gas.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to an aqueous liquid preparation. [Background technology]

[0002] Eye drops, a type of aqueous liquid preparation, are defined in the Japanese Pharmacopoeia as "sterile preparations that ensure sterility for application to ocular tissues such as the conjunctival sac," and must pass sterility tests, insoluble foreign body tests, and insoluble particulate tests. Eye drops also have a set expiration date for use before opening, typically three years. During this expiration date, the active ingredient content, pH, viscosity, and other properties must be maintained constant. For example, methods reported for suppressing viscosity reduction over time include incorporating thiosulfate (Patent Document 1) and incorporating xanthines (caffeine, theophylline, theobromine, proxyphylline, pentoxifylline, etc.) with aspartic acid or a salt thereof (Patent Document 2). [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Japanese Patent Application Laid-Open No. 2007-269934 [Patent Document 2] Japanese Patent Application Laid-Open No. 2003-201241 Summary of the Invention [Problem to be solved by the invention]

[0004] An object of the present invention is to provide a technology for suppressing a decrease in viscosity over time in an aqueous liquid preparation containing a water-soluble polymer. [Means for solving the problem]

[0005] That is, one embodiment of the present invention is the aqueous liquid preparation shown below. Item 1-1. An aqueous liquid preparation containing a water-soluble polymer, which is contained in a resin container that has been sterilized with hydrogen peroxide gas. Item 1-2. The aqueous liquid preparation according to Item 1-1, wherein the resin is at least one selected from the group consisting of polyethylene (PE) and polypropylene (PP). Item 1-3. The aqueous liquid preparation according to Item 1-1 or 1-2, wherein the resin is polypropylene (PP). Item 1-4: The aqueous liquid preparation according to any one of Items 1-1 to 1-3, wherein the water-soluble polymer is a cellulose-based water-soluble polymer. Item 1-5. The aqueous liquid preparation according to any one of Items 1-1 to 1-4, wherein the water-soluble polymer is one or more selected from the group consisting of hydroxypropylmethylcellulose, hydroxyethylcellulose, carboxymethylcellulose, and methylcellulose. Item 1-6. The aqueous liquid preparation according to any one of Items 1-1 to 1-5, wherein the concentration of the water-soluble polymer in the aqueous liquid preparation is about 0.0001 w / v % to about 10 w / v %. Item 1-7. The aqueous liquid preparation according to any one of Items 1-1 to 1-6, wherein the concentration of the water-soluble polymer in the aqueous liquid preparation is greater than about 0.01 w / v % and not more than about 10 w / v %. Item 1-8. The aqueous liquid preparation according to any one of Items 1-1 to 1-7, which is an eye drop. Item 1-9. The aqueous liquid preparation according to any one of Items 1-1 to 1-8, which has a pH of about 4 to about 8. Item 1-10: The aqueous liquid preparation according to any one of Items 1-1 to 1-9, wherein the resin container is a multi-dose container. Item 1-11. The aqueous liquid preparation according to any one of Items 1-1 to 1-10, which has a viscosity of about 1 to about 6000 mPa·s. Item 1-12. The aqueous liquid preparation according to any one of Items 1-1 to 1-11, wherein the viscosity of the aqueous liquid preparation is maintained at about 75% or more after storage at 50°C for 8 weeks.

[0006] Furthermore, one embodiment of the present invention is the following pharmaceutical product. Item 2-1. A pharmaceutical product in which an aqueous liquid agent containing a water-soluble polymer is contained in a resin container that has been sterilized with hydrogen peroxide gas. Item 2-2. The pharmaceutical product according to Item 2-1, wherein the resin is at least one selected from the group consisting of polyethylene (PE) and polypropylene (PP). Item 2-3. The pharmaceutical product according to Item 2-1 or 2-2, wherein the resin is polypropylene (PP). Item 2-4. The pharmaceutical product according to any one of Items 2-1 to 2-3, wherein the water-soluble polymer is a cellulose-based water-soluble polymer. Item 2-5. The pharmaceutical product according to any one of Items 2-1 to 2-4, wherein the water-soluble polymer is one or more selected from the group consisting of hydroxypropylmethylcellulose, hydroxyethylcellulose, carboxymethylcellulose, and methylcellulose. Item 2-6. The pharmaceutical product according to any one of Items 2-1 to 2-5, wherein the concentration of the water-soluble polymer in the aqueous liquid preparation is about 0.0001 w / v % to about 10 w / v %. Item 2-7. The pharmaceutical product according to any one of Items 2-1 to 2-6, wherein the concentration of the water-soluble polymer in the aqueous liquid preparation is about 0.01 w / v % to about 10 w / v % or less. Item 2-8. The pharmaceutical product according to any one of Items 2-1 to 2-7, wherein the aqueous liquid preparation is an eye drop. Item 2-9. The pharmaceutical product according to any one of Items 2-1 to 2-8, wherein the aqueous liquid preparation has a pH of about 4 to about 8. Item 2-10. The pharmaceutical product according to any one of Items 2-1 to 2-9, wherein the resin container is a multi-dose container. Item 2-11. The pharmaceutical product according to any one of Items 2-1 to 2-10, wherein the viscosity of the aqueous liquid preparation is about 1 to about 6000 mPa·s. Item 2-12. The pharmaceutical product according to any one of Items 2-1 to 2-11, wherein the viscosity of the aqueous liquid preparation is maintained at about 75% or more after storage at 50°C for 8 weeks.

[0007] Another embodiment of the present invention is a method for producing a pharmaceutical product, as described below. Item 3-1. A method for producing a pharmaceutical product, comprising the step of placing an aqueous liquid preparation containing a water-soluble polymer in a resin container that has been sterilized with hydrogen peroxide gas. Item 3-2. The manufacturing method according to Item 3-1, wherein the resin is at least one selected from the group consisting of polyethylene (PE) and polypropylene (PP). Item 3-3. The method according to Item 3-1 or 3-2, wherein the resin is polypropylene (PP). Item 3-4. The method according to any one of Items 3-1 to 3-3, wherein the water-soluble polymer is a cellulose-based water-soluble polymer. Item 3-5. The production method according to any one of Items 3-1 to 3-4, wherein the water-soluble polymer is one or more selected from the group consisting of hydroxypropylmethylcellulose, hydroxyethylcellulose, carboxymethylcellulose, and methylcellulose. Item 3-6. The method according to any one of Items 3-1 to 3-5, wherein the concentration of the water-soluble polymer in the aqueous liquid preparation is about 0.0001 w / v % to about 10 w / v %. Item 3-7. The method according to any one of Items 3-1 to 3-6, wherein the concentration of the water-soluble polymer in the aqueous liquid preparation is greater than about 0.01 w / v % and not more than about 10 w / v %. Item 3-8. The method according to any one of Items 3-1 to 3-7, wherein the aqueous liquid preparation is an eye drop. Item 3-9. The method according to any one of Items 3-1 to 3-8, wherein the aqueous liquid preparation has a pH of about 4 to about 8. Item 3-10. The method according to any one of Items 3-1 to 3-9, wherein the resin container is a multi-dose container. Item 3-11. The method according to any one of Items 3-1 to 3-10, wherein the aqueous liquid preparation has a viscosity of about 1 to about 6000 mPa·s. Item 3-12. The method according to any one of Items 3-1 to 3-11, wherein the viscosity of the aqueous liquid preparation is maintained at about 75% or more after storage of the pharmaceutical product at 50°C for 8 weeks.

[0008] Another embodiment of the present invention is a method for suppressing a decrease in viscosity of an aqueous liquid preparation, as described below. Item 4-1. A method for suppressing a decrease in viscosity of an aqueous liquid preparation, comprising a step of storing an aqueous liquid preparation containing a water-soluble polymer in a resin container that has been sterilized with hydrogen peroxide gas. Item 4-2. The method according to Item 4-1, wherein the resin is at least one selected from the group consisting of polyethylene (PE) and polypropylene (PP). Item 4-3. The method according to Item 4-1 or 4-2, wherein the resin is polypropylene (PP). Item 4-4. The method according to any one of Items 4-1 to 4-3, wherein the water-soluble polymer is a cellulose-based water-soluble polymer. Item 4-5. The method according to any one of Items 4-1 to 4-4, wherein the water-soluble polymer is one or more selected from the group consisting of hydroxypropylmethylcellulose, hydroxyethylcellulose, carboxymethylcellulose, and methylcellulose. Item 4-6. The method according to any one of Items 4-1 to 4-5, wherein the concentration of the water-soluble polymer in the aqueous liquid preparation is about 0.0001 w / v % to about 10 w / v %. Item 4-7. The method according to any one of Items 4-1 to 4-6, wherein the concentration of the water-soluble polymer in the aqueous liquid preparation is greater than about 0.01 w / v % and not more than about 10 w / v %. Item 4-8. The method according to any one of Items 4-1 to 4-7, wherein the aqueous liquid preparation is an eye drop. Item 4-9. The method according to any one of Items 4-1 to 4-8, wherein the aqueous liquid preparation has a pH of about 4 to about 8. Item 4-10. The method according to any one of Items 4-1 to 4-9, wherein the resin container is a multi-dose container. Item 4-11. The method according to any one of Items 4-1 to 4-10, wherein the viscosity of the aqueous liquid preparation is about 1 to about 6000 mPa·s. Item 4-12. The method according to any one of Items 4-1 to 4-11, wherein the viscosity of the aqueous liquid preparation is maintained at about 75% or more after the aqueous liquid preparation is stored in the resin container at 50°C for 8 weeks.

[0009] Another embodiment of the present invention is a method for improving the stability of an aqueous liquid preparation, as described below. Item 5-1. A method for improving the stability of an aqueous liquid preparation, comprising the step of placing an aqueous liquid preparation containing a water-soluble polymer in a resin container that has been sterilized with hydrogen peroxide gas. Item 5-2. The method according to Item 5-1, wherein the resin is at least one selected from the group consisting of polyethylene (PE) and polypropylene (PP). Item 5-3. The method according to Item 5-1 or 5-2, wherein the resin is polypropylene (PP). Item 5-4. The method according to any one of Items 5-1 to 5-3, wherein the water-soluble polymer is a cellulose-based water-soluble polymer. Item 5-5. The method according to any one of Items 5-1 to 5-4, wherein the water-soluble polymer is one or more selected from the group consisting of hydroxypropylmethylcellulose, hydroxyethylcellulose, carboxymethylcellulose, and methylcellulose. Item 5-6. The method according to any one of Items 5-1 to 5-5, wherein the concentration of the water-soluble polymer in the aqueous liquid preparation is about 0.0001 w / v % to about 10 w / v %. Item 5-7. The method according to any one of Items 5-1 to 5-6, wherein the concentration of the water-soluble polymer in the aqueous liquid preparation is greater than about 0.01 w / v % and not more than about 10 w / v %. Item 5-8. The method according to any one of Items 5-1 to 5-7, wherein the aqueous liquid preparation is an eye drop. Item 5-9. The method according to any one of Items 5-1 to 5-8, wherein the aqueous liquid preparation has a pH of about 4 to about 8. Item 5-10: The method according to any one of Items 5-1 to 5-9, wherein the resin container is a multi-dose container. Item 5-11. The method according to any one of Items 5-1 to 5-10, wherein the viscosity of the aqueous liquid preparation is about 1 to about 6000 mPa·s. Item 5-12. The method according to any one of Items 5-1 to 5-11, wherein the viscosity of the aqueous liquid preparation is maintained at about 75% or more after the aqueous liquid preparation is stored in the resin container at 50°C for 8 weeks.

[0010] Another embodiment of the present invention is the use of a resin container sterilized with hydrogen peroxide gas, as described below. Item 6-1. Use of a resin container sterilized with hydrogen peroxide gas to prevent a decrease in viscosity of an aqueous liquid formulation containing a water-soluble polymer. Item 6-2. The use according to Item 6-1, wherein the resin is one or more selected from the group consisting of polyethylene (PE) and polypropylene (PP). Item 6-3. The use according to Item 6-1 or 6-2, wherein the resin is polypropylene (PP). Item 6-4. The use according to any one of Items 6-1 to 6-3, wherein the water-soluble polymer is a cellulose-based water-soluble polymer. Item 6-5. The use according to any one of Items 6-1 to 6-4, wherein the water-soluble polymer is one or more selected from the group consisting of hydroxypropylmethylcellulose, hydroxyethylcellulose, carboxymethylcellulose, and methylcellulose. Item 6-6. The use according to any one of Items 6-1 to 6-5, wherein the concentration of the water-soluble polymer in the aqueous liquid preparation is about 0.0001 w / v % to about 10 w / v %. Item 6-7. The use according to any one of Items 6-1 to 6-6, wherein the concentration of the water-soluble polymer in the aqueous liquid preparation is greater than about 0.01 w / v % and not more than about 10 w / v %. Item 6-8. The use according to any one of Items 6-1 to 6-7, wherein the aqueous liquid preparation is an eye drop. Item 6-9. The use according to any one of Items 6-1 to 6-8, wherein the aqueous liquid preparation has a pH of about 4 to about 8. Item 6-10. The use according to any one of Items 6-1 to 6-9, wherein the resin container is a multi-dose container. Item 6-11. The use according to any one of Items 6-1 to 6-10, wherein the viscosity of the aqueous liquid preparation is about 1 to about 6000 mPa·s. Item 6-12. The use according to any one of Items 6-1 to 6-11, wherein the viscosity of the aqueous liquid preparation is maintained at about 75% or more after the aqueous liquid preparation is stored in the resin container at 50°C for 8 weeks. [Effects of the Invention]

[0011] According to the present invention, it is possible to suppress a decrease in viscosity over time in an aqueous liquid preparation containing a water-soluble polymer. DETAILED DESCRIPTION OF THE INVENTION

[0012] 1.Definition It should be understood that the terms used in this specification are used in the sense commonly used in the art unless otherwise specified. Therefore, unless otherwise defined, all technical and scientific terms used in this specification have the same meaning as commonly understood by those skilled in the art to which this invention belongs. If the description in this specification contradicts the meaning commonly used in the art, this specification (including definitions) shall prevail.

[0013] As used herein, the term "water-soluble polymer" refers to a polymer that is soluble in water.

[0014] As used herein, the term "aqueous liquid preparation" refers to a preparation that contains water as a base and is in a liquid state.

[0015] As used herein, a "resin container sterilized with hydrogen peroxide gas" refers to a resin container that has been sterilized by contact with hydrogen peroxide gas. A resin container sterilized with hydrogen peroxide gas may be one in which the container body, including the storage section that stores an aqueous liquid agent, has been sterilized with hydrogen peroxide gas, and other components, such as a nozzle and a lid, that are provided as needed, may have been subjected to other sterilization treatments. A resin container may be one in which the container body is made of resin, and other components, such as a nozzle and a lid, that are provided as needed, may be made of other materials. Furthermore, it is also sufficient that at least the inner wall of the container body that comes into contact with the stored aqueous liquid agent is made of resin.

[0016] In this specification, the term "cellulose-based water-soluble polymer" refers to a type of water-soluble polymer, a cellulose derivative in which the hydroxyl groups of cellulose are at least partially converted to other substituents.

[0017] In this specification, unless otherwise specified, the term "about" means ±10% of the following numerical value.

[0018] In this specification, the unit of concentration of each component, "w / v%", indicates the mass-to-volume percentage in the Japanese Pharmacopoeia, 18th Edition, and is synonymous with g / 100 mL.

[0019] In this specification, the term "multi-dose container" refers to a container that is filled with an amount of aqueous liquid preparation sufficient for multiple uses and can be used repeatedly.

[0020] As used herein, "viscosity of aqueous liquid formulations" refers to the value measured 90 seconds after the start of measurement at 30°C and a rotational speed of 100 rpm according to "2.1.3. Cone-plate rotational viscometer (cone-plate type viscometer)" in Method 2 of the Japanese Pharmacopoeia General Test Methods for Viscosity Measurement <2.53>. However, if the viscosity measured at 30°C and a rotational speed of 100 rpm exceeds the upper limit of measurable viscosity (146.3 mPa·s), "viscosity of aqueous liquid formulations" refers to the value measured 90 seconds after the start of measurement at 30°C and a rotational speed of 2.5 rpm. Specifically, the viscosity of aqueous liquid formulations is measured using a TVE-25 viscometer (model: TVE-25L) manufactured by Toki Sangyo Co., Ltd.

[0021] In this specification, the term "viscosity retention rate (%)" refers to the ratio of the viscosity of an aqueous liquid preparation immediately after preparation to the viscosity of the aqueous liquid preparation immediately after preparation, after storage at 50°C under light-shielded conditions for 8 weeks, and is calculated according to the following formula (1). The accelerated deterioration test will be described later. Viscosity retention rate (%) = Viscosity after 8 weeks of storage (mPa·s) / Viscosity before accelerated aging test (mPa·s) × 100 Formula (1)

[0022] As used herein, the term "pharmaceutical product" refers to a product in which an aqueous liquid formulation is contained in a container, and the aqueous liquid formulation is a pharmaceutical composition. The term "pharmaceutical composition" refers to a composition for medical use.

[0023] In this specification, the expression "viscosity reduction over time" refers to the decrease in viscosity of an aqueous liquid preparation after storage for a certain period of time compared to before storage.

[0024] In this specification, expressions such as "suppression of viscosity decrease over time" refer to suppression of viscosity decrease over time compared to an aqueous liquid preparation of the same composition that has been sterilized by electron beam and is contained in a container made of the same material.

[0025] In this specification, expressions such as "improving the stability of an aqueous liquid" refer to suppressing a decrease in the viscosity of an aqueous liquid containing a water-soluble polymer and maintaining the viscosity of the aqueous liquid stably.

[0026] 2. Description of the Preferred Embodiment Although the following description of preferred embodiments is given, it should be understood that these embodiments are merely examples of the present invention and that the scope of the present invention is not limited to such preferred embodiments. It should also be understood that those skilled in the art can easily make modifications, changes, etc. within the scope of the present invention by referring to the following preferred embodiments. Those skilled in the art can combine any of these embodiments as appropriate.

[0027] 3. Water-based liquid Aqueous liquid preparations such as eye drops often contain water-soluble polymers to impart viscosity to extend the residence time of the compounded components in the body, improve the dispersibility of the compounded components, and improve the feel when used. However, it is known that aqueous liquid preparations containing water-soluble polymers may lose viscosity over time. This decrease in viscosity may reduce the residence time of the compounded components in the body, the dispersibility of the compounded components, the feel when used, and other aspects. Therefore, it is extremely important to provide a technology that suppresses the decrease in viscosity over time in aqueous liquid preparations containing water-soluble polymers.

[0028] Under these circumstances, the present inventors have found that the decrease in viscosity over time of an aqueous liquid preparation containing a water-soluble polymer can be suppressed by storing the preparation in a container that has been sterilized with hydrogen peroxide gas.

[0029] That is, in one embodiment, the present invention is an aqueous liquid preparation containing a water-soluble polymer, which is contained in a resin container that has been sterilized with hydrogen peroxide gas. The aqueous liquid preparation of the present invention will be described below.

[0030] ·Water-soluble polymer The aqueous liquid preparation of the present invention contains a water-soluble polymer. The water-soluble polymer used in the present invention may be any polymer capable of imparting a desired viscosity to an aqueous liquid preparation, and is not particularly limited as long as it is pharmaceutically acceptable, but examples thereof include water-soluble polymers used as thickeners or viscosifiers. Examples of such water-soluble polymers include cellulose-based water-soluble polymers, polyvinyl-based water-soluble polymers, polyoxyalkylene glycol-based water-soluble polymers, and polysaccharides. These water-soluble polymers may be used alone or in combination of two or more.

[0031] Among these water-soluble polymers, from the viewpoint of more effectively suppressing a decrease in viscosity over time, preferred are cellulose-based water-soluble polymers and polyvinyl-based water-soluble polymers, and more preferred are cellulose-based water-soluble polymers.

[0032] Examples of the cellulose-based water-soluble polymer include hydroxypropyl methylcellulose (also called hypromellose, hereinafter sometimes referred to as "HPMC"), hydroxyethyl cellulose (hereinafter sometimes referred to as "HEC"), carboxymethyl cellulose (also called carmellose, hereinafter sometimes referred to as "CMC"), methyl cellulose (hereinafter sometimes referred to as "MC"), hydroxymethyl cellulose, hydroxypropyl cellulose, sulfonated cellulose derivatives, and salts thereof. These cellulose-based water-soluble polymers may be used alone or in combination of two or more.

[0033] Among these cellulose-based water-soluble polymers, from the viewpoint of more effectively suppressing a decrease in viscosity over time, one or more selected from the group consisting of hydroxypropylmethylcellulose, hydroxyethylcellulose, carboxymethylcellulose, and methylcellulose are preferred, and methylcellulose is more preferred.

[0034] Examples of the water-soluble cellulose polymer in the form of a salt include alkali metal salts, and alkali metal salts of CMC include sodium CMC, potassium CMC, etc. From the viewpoint of more effectively suppressing a decrease in viscosity over time, the alkali metal salt of CMC is preferably sodium CMC.

[0035] As used herein, the term "hydroxypropyl methylcellulose" is synonymous with hypromellose and refers to cellulose in which at least a portion of the hydroxyl groups has been hydroxypropyl-etherified and / or methyl-etherified. The hydroxypropyl methylcellulose is not particularly limited, and any hydroxypropyl methylcellulose having different degrees of substitution of methoxy groups and hydroxypropoxy groups, molecular weight, viscosity, etc. may be used, and these may be used alone or in combination of two or more types.

[0036] The degree of substitution type of hydroxypropyl methylcellulose may be any of 1828, 2208, 2906, and 2910, but is preferably 2910 or 2208. The molecular weight of hydroxypropylmethylcellulose is, for example, about 10,000 to about 500,000, preferably about 100,000 to about 500,000, and more preferably about 300,000 to about 500,000, in terms of weight average molecular weight. The viscosity of hydroxypropyl methylcellulose is preferably about 50 to about 100,000 mPa·s, more preferably about 100 to about 15,000 mPa·s. Here, the viscosity of hydroxypropyl methylcellulose is a value measured in accordance with the 18th Edition of the Japanese Pharmacopoeia (indicated viscosity: the viscosity of a 2% aqueous solution of the Japanese Pharmacopoeia at 20°C).

[0037] In this specification, the term "hydroxyethyl cellulose" refers to cellulose in which at least a portion of the hydroxyl groups has been hydroxyethyl etherified. The hydroxyethyl cellulose is not particularly limited, and any hydroxyethyl cellulose having different molar substitution of hydroxyethoxy groups (average number of moles of hydroxyethoxy groups added per anhydroglucose unit), degree of substitution (average number of hydroxyl groups reacted with hydroxyethyl groups per anhydroglucose unit in hydroxyethyl cellulose), molecular weight, viscosity, etc. may be used, and these may be used alone or in combination of two or more kinds.

[0038] The molar substitution degree of the hydroxyethoxy group of hydroxyethyl cellulose is, for example, about 1.5 to about 3.0. The degree of substitution of hydroxyethyl cellulose is usually about 30 to about 70%, preferably about 40 to about 60%. The molecular weight of hydroxyethyl cellulose is, for example, about 10,000 to about 1,000,000, preferably about 100,000 to about 1,000,000, and more preferably about 600,000 to about 800,000, in terms of weight average molecular weight. The viscosity of hydroxyethyl cellulose is preferably about 1 to about 50,000 mPa·s, more preferably about 5,000 to about 20,000 mPa·s. Here, the viscosity of hydroxyethyl cellulose is a value measured in accordance with the 18th edition of the Japanese Pharmacopoeia (indicated viscosity: the viscosity of a 2% aqueous solution of the Japanese Pharmacopoeia at 20°C).

[0039] In this specification, the term "carboxymethyl cellulose" refers to cellulose in which at least a portion of the hydroxyl groups has been carboxymethyl etherified. The carboxymethyl cellulose and / or its salt is not particularly limited, and any carboxymethyl cellulose having different degrees of substitution (average number of hydroxyl groups reacted with carboxymethyl groups per anhydroglucose unit in CMC), molecular weight, viscosity, etc. may be used, and these may be used alone or in combination of two or more types.

[0040] The degree of substitution of carboxymethyl cellulose and / or a salt thereof is, for example, about 0.3 to about 1.5, preferably about 0.4 to about 1.0, and more preferably about 0.5 to about 0.8. The molecular weight of carboxymethyl cellulose and / or a salt thereof is, for example, about 20,000 to about 700,000, preferably about 30,000 to about 100,000, and more preferably about 35,000 to about 75,000, in terms of weight average molecular weight. The viscosity of carboxymethyl cellulose and / or its salt is usually about 25 to about 1000 mPa·s, and preferably about 500 to about 900 mPa·s. Here, the viscosity of carboxymethyl cellulose refers to the viscosity of a 2% aqueous solution of CMC at 25°C, measured using a BM type viscometer.

[0041] In this specification, "methyl cellulose" refers to cellulose in which at least a portion of the hydroxyl groups has been methyl-etherified. The methylcellulose is not particularly limited, and any methylcellulose having different methoxy group substitution rates, degree of substitution (average number of hydroxyl groups reacted with methyl groups per anhydroglucose unit in methylcellulose), molecular weight, viscosity, etc. may be used, and these may be used alone or in combination of two or more types.

[0042] The substitution rate of methoxy groups in methylcellulose is usually about 20 to about 40%, and preferably about 26 to about 33%. The degree of substitution of methylcellulose is usually about 1.5 to about 3.0%, preferably about 1.7 to about 1.9%. The molecular weight of methylcellulose is, for example, about 10,000 to about 500,000, preferably about 100,000 to about 500,000, and more preferably about 300,000 to about 500,000, in terms of weight average molecular weight. The viscosity of methylcellulose is usually about 1 to about 10,000 mPa·s, preferably about 100 to about 15,000 mPa·s, more preferably about 500 to about 10,000 mPa·s, even more preferably about 1,000 to about 7,000 mPa·s, and particularly preferably about 3,000 to about 5,600 mPa·s. Here, the viscosity of methylcellulose is the value measured in accordance with the 18th Edition of the Japanese Pharmacopoeia (indicated viscosity: the viscosity of a 2% aqueous solution of the Japanese Pharmacopoeia at 20°C).

[0043] In this specification, the term "water-soluble polyvinyl polymer" refers to a type of water-soluble polymer, a polymer compound obtained by homopolymerizing or copolymerizing a monomer having a vinyl group. Examples of the polyvinyl-based water-soluble polymer include polyvinylpyrrolidone, polyvinyl alcohol, carboxyvinyl polymer (crosslinked polyacrylic acid polymer, etc.), etc. These polyvinyl-based polymer compounds can be used alone or in combination of two or more.

[0044] In this specification, the term "water-soluble polyoxyalkylene glycol polymer" refers to a water-soluble polymer having a structure in which polyoxyalkylene glycol is homopolymerized or copolymerized. Examples of the polyoxyalkylene glycol-based water-soluble polymer include polyalkylene glycols such as polyethylene glycol and polypropylene glycol, and copolymers thereof. The molecular weight of the polyoxyalkylene glycol-based water-soluble polymer is usually about 200 to about 20,000, preferably about 1,000 to about 10,000, and more preferably about 3,000 to about 5,000. Examples include polyethylene glycol 300, polyethylene glycol 400, and polyethylene glycol 4000.

[0045] As used herein, the term "polysaccharide" refers to a type of water-soluble polymer, a natural polymer in which monosaccharides are polymerized via glycosidic bonds. Examples of polysaccharides include xanthan gum, chondroitin sulfate, hyaluronic acid, alginic acid, etc. These polysaccharides may be in the form of a salt. Examples of polysaccharides in the form of a salt include alkali metal salts such as sodium chondroitin sulfate, sodium hyaluronate, and sodium alginate. These polysaccharides may be used alone or in combination of two or more.

[0046] The concentration of the water-soluble polymer in the aqueous liquid preparation may be appropriately determined depending on the type of water-soluble polymer used, the viscosity to be imparted, and the like. The concentration of the water-soluble polymer in the aqueous liquid preparation is preferably about 0.0001 w / v% or more, more preferably about 0.04 w / v% or more, even more preferably about 0.4 w / v% or more, and preferably about 10 w / v% or less, more preferably about 5 w / v% or less, even more preferably about 1.5 w / v% or less, based on the total amount of the water-soluble polymer. The lower limit and the upper limit can be arbitrarily combined, for example, about 0.001 w / v% to about 10 w / v%, about 0.01 w / v% to about 8 w / v%, etc., preferably about 0.04 w / v% to about 5 w / v%, more preferably about 0.1 w / v% to about 2 w / v%, even more preferably about 0.4 w / v% to about 1.5 w / v%. In a preferred embodiment of the present invention, the concentration of the water-soluble polymer in the aqueous liquid preparation is greater than about 0.01 w / v % and not more than about 10 w / v % in terms of the total amount of the water-soluble polymer.

[0047] Other additives The aqueous liquid preparation may further contain additives such as an isotonic agent, a polyhydric alcohol (excluding polyoxyalkylene glycol-based water-soluble polymers), a surfactant, a chelating agent, a buffer, an antiseptic or preservative, a cooling agent, a stabilizer, and a pH adjuster, as needed.

[0048] Pharmacological ingredients The aqueous liquid preparation contains a pharmacological ingredient and is used as a pharmaceutical composition. Examples of the pharmacological ingredient of the aqueous liquid preparation include, when used as an eye drop, isopropyl unoprostone, carteolol, distigmine, dipivefrin, tafluprost, timolol, travoprost, dorzolamide, nipradilol, bimatoprost, pilocarpine, bunazosin, brimonidine, brinzolamide, betaxolol, latanoprost, ripasudil, netarsudil, levobunolol or a salt thereof for the treatment of glaucoma; acyclovir, erythromycin, off-label use, etc. For antibacterial and antiviral treatment such as loxacin, gatifloxacin, chloramphenicol, gentamicin, dibekacin, cefmenoxime, tosufloxacin, tobramycin, norfloxacin, vancomycin, pimaricin, azithromycin, moxifloxacin, levofloxacin, lomefloxacin or their salts; dexamethasone, dexamethasone metasulfobenzoate, dexamethasone phosphate, hydrocortisone acetate, fradiomycin, furafenol Anti-inflammatory treatments such as fluoromethorone, prednisolone acetate, betamethasone phosphate, azulene sulfonic acid, glycyrrhizinic acid, diclofenac, nepafenac, pranoprofen, bromfenac, or their salts; dry eye and corneal treatments such as chondroitin sulfate, diquafosol, hyaluronic acid, flavin adenine dinucleotide, rebamipide, or their salts; ashitazanolast, amlexanox, ibudilast, chlorpheniramine, diphenhydramine, estrogen, phenytoin ... Antiallergic treatments such as pinastine, olopatadine, cromoglycate, ketotifen, cyclosporine, tacrolimus, tranilast, pemirolast, levocabastine or their salts; and cataract, eye strain and other treatments such as atropine, oxybuprocaine, oxymetazoline, glutathione, cyanocobalamin, cyclopentolate, tropicamide, naphazoline, neostigmine, pirenoxine, phenylephrine, lysozyme, zinc sulfate or their salts.

[0049] These pharmacological ingredients may be used alone or in combination of two or more. The concentrations of these pharmacological ingredients may be appropriately determined depending on the type of pharmacological ingredient used, the medicinal effect to be imparted, etc. Furthermore, the water-soluble polymer may be contained in the aqueous liquid preparation as a pharmacological ingredient or as an additive.

[0050] ·viscosity The viscosity of the aqueous liquid preparation is not particularly limited, but is, for example, about 1 to about 6000 mPa·s. For example, it can be about 1 to about 3000 mPa·s, about 1 to about 1000 mPa·s, about 1 to about 500 mPa·s, about 1 to about 250 mPa·s, about 1 to about 100 mPa·s, about 1 to about 90 mPa·s, about 1 to about 80 mPa·s, about 1 to about 70 mPa·s, about 1 to about 60 mPa·s, or about 1 to about 50 mPa·s. When the aqueous liquid preparation is an ophthalmic composition such as eye drops or eyewash, from the viewpoint of usability, the viscosity is preferably about 1 to about 1000 mPa·s, more preferably about 1 to about 500 mPa·s, and even more preferably about 1 to about 100 mPa·s. The viscosity of the aqueous liquid preparation is preferably that after storage.

[0051] ·Viscosity maintenance rate The viscosity retention rate of the aqueous liquid preparation after storage at 50°C for 8 weeks is not particularly limited, but is, for example, 65% or more, 70% or more, preferably 75% or more, more preferably 80% or more, and even more preferably 85% or more. The viscosity retention rate of the aqueous liquid preparation contained in a polyethylene container after storage at 50°C for 8 weeks is, for example, 65% or more, preferably 70% or more, more preferably 75% or more, and even more preferably 80% or more. The viscosity retention rate of the aqueous liquid preparation contained in a polypropylene container after storage at 50°C for 8 weeks is, for example, 60% or more, 65% or more, 70% or more, preferably 75% or more, more preferably 80% or more, even more preferably 85% or more, particularly preferably 90% or more, and even more preferably 95% or more.

[0052] pH The pH of the aqueous liquid preparation is not particularly limited as long as it is pharmaceutically acceptable, and may be, for example, about 4 to about 8 at 25° C. When the aqueous liquid preparation is an ophthalmic composition such as eye drops or eyewash, the pH at 25° C. is preferably about 5.5 to about 8.5, more preferably about 6.0 to about 8.0, and even more preferably about 6.5 to about 7.5, from the viewpoint of further reducing irritation to the eyes that can be applied to the ocular mucosa.

[0053] Osmolality / osmolality ratio The osmotic pressure of the aqueous liquid preparation is not particularly limited as long as it is applicable to the intended use. For example, when the aqueous liquid preparation is an ophthalmic aqueous liquid preparation, the osmotic pressure can be about 250 to about 350 mOsm / kg.

[0054] The osmotic pressure ratio of the aqueous solution is not particularly limited as long as it is applicable to the intended use. For example, when the aqueous solution is an ophthalmic aqueous solution, the osmotic pressure ratio is about 0.85 to about 1.15. From the viewpoint of alleviating eye irritation, the osmotic pressure ratio is preferably about 0.9 to about 1.1, more preferably about 1.0.

[0055] Formulation The formulation form of the aqueous liquid preparation is not particularly limited, and may be any of an aqueous solution, a suspension, an emulsion, etc., but is preferably an aqueous solution.

[0056] Aqueous liquid preparations can be prepared into pharmaceutical compositions for various uses, such as ophthalmology, dentistry, otolaryngology, dermatology, etc., and can be used as topical administration preparations. One embodiment of the aqueous liquid preparation includes a composition for ophthalmology, dentistry, otolaryngology, or dermatology, and preferably includes an aqueous ophthalmology solution.

[0057] Examples of aqueous ophthalmic solutions include eye drops, eyewashes, solutions for contact lenses, injections, etc. Among these, eye drops are preferred. When the aqueous liquid preparation is used as an eye drop, a few drops may be instilled into the eyes once or multiple times a day.

[0058] ·Manufacturing method Aqueous liquid preparations may be prepared according to known preparation methods depending on the intended use, for example, by the method described in the General Provisions for Preparations of the Japanese Pharmacopoeia, 18th Edition.

[0059] Specifically, in one embodiment, the method for producing an aqueous liquid preparation comprises a step of blending a water-soluble polymer with a pharmaceutically acceptable aqueous medium. The term "pharmaceutically acceptable aqueous medium" refers to a pharmaceutically acceptable aqueous medium, such as purified water. In the blending step, the order in which the components are blended is not particularly limited, and the components may be blended sequentially or simultaneously. After the blending step, a sterilization step such as filtration sterilization, high-pressure steam sterilization, electron beam sterilization, or gamma ray sterilization may be performed as necessary.

[0060] Resin containers sterilized with hydrogen peroxide gas The aqueous liquid preparation of the present invention is contained in a resin container that has been sterilized with hydrogen peroxide gas. By combining a specific aqueous liquid preparation with a specific container in this manner, it is possible to suppress viscosity reduction over time.

[0061] Hydrogen peroxide gas sterilization, also known as hydrogen peroxide vapor sterilization, is a sterilization method in which liquid hydrogen peroxide is evaporated through a heated vaporizer and containers, etc., are exposed to the hydrogen peroxide vapor. It can be either hydrogen peroxide gas plasma sterilization or hydrogen peroxide gas low-temperature sterilization. The conditions for hydrogen peroxide gas sterilization, such as temperature, humidity, pressure, the number of times hydrogen peroxide gas is injected into the sterilization chamber, exposure time to hydrogen peroxide gas, and hydrogen peroxide gas concentration, are not particularly limited as long as sufficient sterilization can be achieved, and may be selected appropriately depending on the characteristics of the containers, etc.

[0062] The concentration of liquid hydrogen peroxide solution used in hydrogen peroxide gas sterilization is, for example, about 10 to about 95 wt %, preferably about 20 to about 80 wt %, and more preferably about 30 to about 60 wt %.

[0063] The gas used in hydrogen peroxide gas sterilization may be hydrogen peroxide gas alone or a mixed gas with other gases such as air or carbon dioxide.

[0064] The temperature for hydrogen peroxide gas sterilization (temperature inside the can) is preferably about 15 to about 60°C, more preferably about 30 to about 60°C, and even more preferably about 40 to about 55°C.

[0065] The humidity (relative humidity) for hydrogen peroxide gas sterilization is preferably about 10 to about 95%, more preferably about 30 to about 80%.

[0066] In hydrogen peroxide gas sterilization, the number of times that hydrogen peroxide gas is injected into the sterilization chamber is, for example, 1 to 5 times, and preferably 2 to 4 times.

[0067] In hydrogen peroxide gas sterilization, the time for which the container is exposed to hydrogen peroxide gas is, for example, about 1 minute to about 12 hours, preferably about 10 minutes to about 6 hours, and more preferably about 30 minutes to about 2 hours.

[0068] The resin container is not particularly limited as long as it is made of a resin material. Examples of resins include polyolefins such as polyethylene (PE), polypropylene (PP), and propylene-ethylene copolymers; polyesters such as polyethylene terephthalate and polybutylene terephthalate; polystyrene, acrylonitrile-butadiene-styrene copolymers, polycarbonate, polymethyl methacrylate, and ethylene-vinyl alcohol copolymers. Polyethylene is further classified according to its density, and examples include low-density polyethylene (LDPE), medium-density polyethylene (MDPE), and high-density polyethylene (HDPE). Among these, from the viewpoint of more effectively suppressing a decrease in viscosity of the aqueous liquid preparation over time, polyolefins are preferred, and one or more selected from the group consisting of polypropylene and polyethylene are more preferred, with polypropylene being particularly preferred.

[0069] The resin container may be transparent, translucent, or opaque, and may be colorless or colored.

[0070] The resin container may be either a multi-dose container or a unit-dose container, but a preferred embodiment is a multi-dose container.

[0071] The resin container may be in the form of an eye dropper, an eyewash container, or the like, depending on the intended use of the aqueous liquid preparation contained therein.

[0072] 4. Pharmaceutical products As one embodiment of the present invention, there is provided a pharmaceutical product in which an aqueous liquid agent containing a water-soluble polymer is contained in a resin container that has been sterilized with hydrogen peroxide gas.

[0073] According to the present invention, by storing an aqueous liquid preparation containing a water-soluble polymer in a resin container that has been sterilized with hydrogen peroxide gas, it is possible to provide a pharmaceutical product in which the viscosity of the aqueous liquid preparation is inhibited from decreasing over time.

[0074] In the present invention, the type and concentration of the water-soluble polymer, the types of other additives and pharmacological ingredients to be blended in the aqueous liquid, the viscosity, pH, osmotic pressure, formulation, production method, etc. of the aqueous liquid are as described in the section "3. Aqueous liquid." In addition, the hydrogen peroxide gas sterilized resin container used in the present invention is also as described in the section "3. Aqueous liquid."

[0075] 5. Manufacturing methods for pharmaceutical products As one embodiment of the present invention, there is provided a method for producing a pharmaceutical product, which includes a step of placing an aqueous liquid preparation containing a water-soluble polymer in a resin container that has been sterilized with hydrogen peroxide gas.

[0076] According to the production method of the present invention, an aqueous liquid preparation containing a water-soluble polymer is contained in a resin container that has been sterilized with hydrogen peroxide gas, thereby making it possible to produce a pharmaceutical product in which the viscosity of the aqueous liquid preparation is inhibited from decreasing over time.

[0077] In the production method of the present invention, the type and concentration of the water-soluble polymer, the types of other additives and pharmacological ingredients to be blended in the aqueous liquid, the viscosity, pH, osmotic pressure, formulation, production method, etc. of the aqueous liquid are as described in the section "3. Aqueous liquid." In addition, the hydrogen peroxide gas-sterilized resin container used in the present invention is also as described in the section "3. Aqueous liquid."

[0078] 6. Methods for preventing viscosity loss of aqueous liquid formulations As one embodiment of the present invention, there is provided a method for suppressing a decrease in viscosity of an aqueous liquid preparation, the method comprising the step of storing an aqueous liquid preparation containing a water-soluble polymer in a resin container that has been sterilized with hydrogen peroxide gas.

[0079] According to the method of the present invention, an aqueous liquid preparation containing a water-soluble polymer can be contained in a resin container that has been sterilized with hydrogen peroxide gas, thereby preventing a decrease in viscosity of the aqueous liquid preparation.

[0080] In the method of the present invention, the type and concentration of the water-soluble polymer, the types of other additives and pharmacological ingredients to be blended in the aqueous liquid, the viscosity, pH, osmotic pressure, formulation, production method, etc. of the aqueous liquid are as described in the section "3. Aqueous liquid." In addition, the hydrogen peroxide gas-sterilized resin container used in the present invention is also as described in the section "3. Aqueous liquid."

[0081] 7. Methods for improving the stability of aqueous liquid formulations As one embodiment of the present invention, there is provided a method for improving the stability of an aqueous liquid preparation, comprising the step of placing an aqueous liquid preparation containing a water-soluble polymer in a resin container that has been sterilized with hydrogen peroxide gas.

[0082] According to the method of the present invention, the stability of an aqueous liquid preparation containing a water-soluble polymer can be improved by storing the aqueous liquid preparation in a resin container that has been sterilized with hydrogen peroxide gas.

[0083] In the method of the present invention, the type and concentration of the water-soluble polymer, the types of other additives and pharmacological ingredients to be blended in the aqueous liquid, the viscosity, pH, osmotic pressure, formulation, production method, etc. of the aqueous liquid are as described in the section "3. Aqueous liquid." In addition, the hydrogen peroxide gas-sterilized resin container used in the present invention is also as described in the section "3. Aqueous liquid."

[0084] 8. Use of resin containers sterilized with hydrogen peroxide gas One embodiment of the present invention provides use of a resin container that has been sterilized with hydrogen peroxide gas to suppress a decrease in viscosity of an aqueous liquid preparation containing a water-soluble polymer.

[0085] The present invention is based on the discovery that a decrease in viscosity of an aqueous liquid preparation containing a water-soluble polymer can be suppressed by storing the aqueous liquid preparation in a resin container that has been sterilized with hydrogen peroxide gas, and that a resin container that has been sterilized with hydrogen peroxide gas is suitable for use in suppressing a decrease in viscosity of an aqueous liquid preparation.

[0086] In the present invention, the type and concentration of the water-soluble polymer, the types of other additives and pharmacological ingredients to be blended in the aqueous liquid, the viscosity, pH, osmotic pressure, formulation, production method, etc. of the aqueous liquid are as described in the section "3. Aqueous liquid." In addition, the hydrogen peroxide gas sterilized resin container used in the present invention is also as described in the section "3. Aqueous liquid." [Example]

[0087] The present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples. Test Example 1: Evaluation of viscosity change of aqueous liquid [Raw materials] An aqueous liquid formulation was prepared using the following ingredients: HPMC 60SH: Hypromellose 2910, trade name "METOLOSE 60SH-4000" (Shin-Etsu Chemical Co., Ltd.) HPMC 90SH: Hypromellose 2208, trade name "METOLOSE 90SH-4000SR" (Shin-Etsu Chemical Co., Ltd.) HEC: Hydroxyethyl cellulose, trade name "Natrosol M Pharm" (manufactured by Ashland Inc.) MC: Methylcellulose, product name "METOLOSE SM-4000" (manufactured by Shin-Etsu Chemical Co., Ltd.) CMC Na: Carmellose sodium, product name "Carboxymethyl Cellulose Sodium Salt (n = approx. 500)" (manufactured by Tokyo Chemical Industry Co., Ltd.)

[0088] [Preparation of aqueous liquid] Each aqueous liquid preparation listed in Table 2 was prepared by the following method. 1. An appropriate amount of purified water was placed in a glass beaker. The glass beaker in 2.1 was heated in a water bath to the following temperature. Hypromellose (HPMC): approx. 80°C Hydroxyethyl cellulose (HEC): approx. 80°C Methylcellulose (MC): approx. 80°C Carmellose sodium (CMC Na): approx. 65°C 3. Each water-soluble polymer was weighed and placed in the glass beaker in step 2. Hypromellose, hydroxyethyl cellulose (concentration 0.4 w / v%), methyl cellulose, and carmellose sodium were stirred with a stirrer. Hydroxyethyl cellulose (concentration 1.5%) was stirred with a propeller. 4. After confirming that hypromellose, hydroxyethyl cellulose, and methyl cellulose were uniformly dispersed, the mixture was cooled in an ice bath to dissolve each water-soluble polymer. Carmellose sodium dissolved at room temperature. 5. The pH of the solution was adjusted to 7 using hydrochloric acid and sodium hydroxide. Purified water was added to a glass beaker (6.5) to bring the total volume to 500 mL.

[0089] [Container sterilization] Hydrogen peroxide gas (VHP) sterilization was performed under the following conditions.

[0090] [Table 1]

[0091] A polyethylene (PE) flat bottle (5 mL) was placed in a paper box and irradiated with an electron beam from above to a dose of 22.2 kGy, and from below to a dose of 21.3 kGy. A polypropylene (PP) flat bottle (5 mL) was placed in the paper box and irradiated with an electron beam to a dose of 17.3 kGy. Electron beam (EB) sterilization was performed under the following conditions. Voltage: 4.8MeV Current: 20mA Cart speed: 6.0m / min

[0092] Each sterilization condition meets the sterility assurance level in the Sterilization Validation Standards (Yakushoku Kannai Hatsu 0215 No. 13).

[0093] [Placing in a container] Five mL of the aqueous solution obtained above was placed in a 5 mL polyethylene (PE) or polypropylene (PP) flat bottle (5 mL capacity) that had been sterilized with hydrogen peroxide gas, and the bottle was sealed to prepare each sample (ophthalmic pharmaceutical product). Each sample obtained above was placed in a paper box. The samples contained in polyethylene containers that had been sterilized with hydrogen peroxide gas were designated Examples 1 to 6, and the samples contained in polypropylene containers that had been sterilized with hydrogen peroxide gas were designated Examples 7 to 12.

[0094] Five mL of the aqueous solution obtained above was placed in an electron beam sterilized polyethylene (PE) or polypropylene (PP) flat bottle (5 mL capacity) and sealed to prepare each sample (ophthalmic pharmaceutical product). Each sample obtained above was placed in a paper box. The samples contained in electron beam sterilized polyethylene containers were designated Comparative Examples 1 to 6, and the samples contained in electron beam sterilized polypropylene containers were designated Comparative Examples 7 to 12.

[0095] [Accelerated aging test] The paper boxes containing the samples were placed on their sides and stored at 50°C ± 2°C for 8 weeks in the dark.

[0096] [Viscosity measurement] The viscosity of each aqueous liquid preparation was measured by the following method before the start of the accelerated deterioration test and after 8 weeks of storage. Viscosity was measured using a TVE-25 viscometer (model: TVE-25L) manufactured by Toki Sangyo Co., Ltd., in accordance with Method 2, Rotational Viscosity Method, of the Japanese Pharmacopoeia's General Test Methods for Viscosity Measurement <2.53>. Measurements were performed at 30°C and a rotational speed of 100 rpm, with the value recorded 90 seconds after the start of measurement. However, since the viscosity of the 1.5% HEC solution exceeded the upper limit of measurable viscosity at a rotational speed of 100 rpm, measurements were performed at a rotational speed of 2.5 rpm. Measurements were performed once for each aqueous liquid formulation.

[0097] The viscosity retention rate (%) was calculated according to the following formula (1). Viscosity retention rate (%) = Viscosity after 8 weeks of storage (mPa·s) / Viscosity before accelerated aging test (mPa·s) × 100 Formula (1)

[0098] [Evaluation results] The results are shown in Table 2. The aqueous liquid formulations contained in containers sterilized with hydrogen peroxide gas had a higher viscosity retention rate than those contained in containers sterilized with electron beams. The viscosity retention rate of the aqueous liquid formulations was particularly high when they were contained in polypropylene containers sterilized with hydrogen peroxide gas.

[0099] [Table 2]

[0100] Formulation example An aqueous liquid preparation having the composition shown in Table 3 is prepared and placed in a container shown in the same table to produce an eye drop.

[0101] [Table 3-1]

[0102] [Table 3-2]

Claims

1. An aqueous liquid preparation containing a water-soluble polymer, the aqueous liquid preparation being contained in a resin container that has been sterilized with hydrogen peroxide gas.

2. 2. The aqueous liquid preparation according to claim 1, wherein the resin is at least one selected from the group consisting of polyethylene (PE) and polypropylene (PP).

3. The aqueous liquid preparation according to claim 1 or 2, wherein the resin is polypropylene (PP).

4. The aqueous liquid preparation according to claim 1 or 2, wherein the water-soluble polymer is a cellulose-based water-soluble polymer.

5. 3. The aqueous liquid preparation according to claim 1, wherein the water-soluble polymer is one or more selected from the group consisting of hydroxypropylmethylcellulose, hydroxyethylcellulose, carboxymethylcellulose, and methylcellulose.

6. 3. The aqueous liquid preparation according to claim 1, wherein the concentration of the water-soluble polymer in the aqueous liquid preparation is about 0.0001 w / v % to about 10 w / v %.

7. 3. The aqueous liquid preparation according to claim 1, wherein the concentration of the water-soluble polymer in the aqueous liquid preparation is greater than about 0.01 w / v % and not more than about 10 w / v %.

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