HK1233184B - Aqueous composition for ophthalmic use - Google Patents

Description

Ophthalmic aqueous composition

Technical Field

The present invention relates to an ophthalmic aqueous composition, a method for suppressing weight change of an ophthalmic resin container containing polybutylene terephthalate, a method for suppressing deterioration of an ophthalmic resin container containing polybutylene terephthalate, and a method for suppressing wetting of an ophthalmic resin container containing polybutylene terephthalate.

Background Art

Polybutylene terephthalate-containing resin (hereinafter referred to as PBT-containing resin in this specification), which is a type of thermoplastic polyester resin and is commonly used as a thermoplastic resin, has excellent moldability and a good balance between physical properties and price. It has been used as a container material for automobiles, motor and electronic parts, semiconductor substrate containers, etc.

In addition, it has been proposed to use a laminated body composed of a PBT film and a thermal adhesive resin layer as a heating packaging bag for storing food composed of liquid and solid substances containing a large amount of water, oil, and sugar, especially a heating packaging bag that does not open even when heated and cooked in a microwave oven (Patent Document 1).

Prior art literature

Patent Literature

Patent Document 1: Japanese Patent Application Laid-Open No. 2006-143223

Summary of the Invention

Thus, the PBT-containing resin has excellent properties, and on the other hand, when used as a container, has the property of absorbing moisture in the content contained in the container.

Furthermore, the PBT-containing resin is hydrolyzed by heat.

An object of the present invention is to provide an ophthalmic aqueous composition that can solve such problems.

The inventors of the present invention have conducted intensive research to address the above-mentioned issues. As a result, they discovered that by incorporating a specific component into an ophthalmic aqueous composition, a PBT resin-containing container housing the composition can be stabilized and deterioration of the container can be prevented. This led to the completion of the present invention. Furthermore, they discovered that an ophthalmic aqueous composition containing the specific component can achieve novel effects such as improved wettability (i.e., suppression of wetting) with respect to PBT resin containers and improved lyophobicity (liquid shedding).

That is, the present invention provides the following solutions:

[1]

An ophthalmic aqueous composition comprising (B) a buffer and (A) at least one selected from the group consisting of polysaccharides, monosaccharides, vitamin _B12 , vitamin B2, ₂ , vitamin A, and one or more vitamins selected from panthenol; one or more oils selected from plant oils, animal oils, and mineral oils; one or more surfactants selected from polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, polyoxyethylene polyoxypropylene glycol, and polyoxyl stearate; one or more antiallergic ingredients selected from tranilast, ketotifen, diphenhydramine, and salts thereof; one or more preservatives selected from chlorhexidine, sorbic acid, and salts thereof; one or more thickening ingredients selected from carboxymethyl cellulose, methyl cellulose, vinyl polymer compounds, and salts thereof; polyols; one or more anti-inflammatory ingredients selected from berberine, azulenesulfonic acid, allantoin, zinc sulfate, and salts thereof; one or more antibacterial agents selected from sulfamethoxazole and its salts; one or more cooling agents selected from eucalyptus oil and bergamot oil,

The ophthalmic aqueous composition is accommodated in (C) a container in which a part or the entirety of the surface in contact with the ophthalmic aqueous composition is molded from a resin containing polybutylene terephthalate.

[2]

The ophthalmic aqueous composition of item [1], wherein, in the above-mentioned component (A), the polysaccharide is one or more selected from alginic acid, gellan gum, xanthan gum, hyaluronic acid, chondroitin sulfate, and salts thereof; the monosaccharide is glucose; the vitamin is one or more selected from cyanocobalamin, retinol, panthenol, flavin adenine dinucleotide, and salts thereof; the oil is one or more selected from sesame oil, castor oil, lanolin, vaseline, and liquid paraffin; the surfactant is one or more selected from polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, polyoxyethylene polyoxypropylene glycol, and polyoxyl stearate; The anti-allergic ingredient is one or more selected from tranilast, ketotifen fumarate, and diphenhydramine hydrochloride; the preservative is one or more selected from chlorhexidine gluconate and potassium sorbate; the thickening ingredient is one or more selected from carboxymethyl cellulose, methyl cellulose, polyvinyl pyrrolidone, carboxyvinyl polymer, and salts thereof; the polyol is one or more selected from propylene glycol, glycerin, and mannitol; the anti-inflammatory ingredient is one or more selected from berberine chloride, sodium azulenesulfonate, allantoin, and zinc sulfate; the antibacterial agent is sodium sulfamethoxazole; and the cooling agent is one or more selected from eucalyptus oil and bergamot oil.

[3]

The ophthalmic aqueous composition according to item [1] or [2], further comprising sodium edetate.

[4]

A method for imparting to an aqueous composition an effect of suppressing weight change of a resin container containing polybutylene terephthalate, wherein (B) a buffer and (A) at least one selected from the group consisting of polysaccharides; monosaccharides; vitamin _{B12, vitamin B2} , and vitamin B6 are coexisted in the aqueous composition. ₂ , vitamin A, and one or more panthenol; one or more oils selected from plant oils, animal oils, and mineral oils; one or more surfactants selected from polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, polyoxyethylene polyoxypropylene glycol, and polyoxyl stearate; one or more antiallergic ingredients selected from tranilast, ketotifen, diphenhydramine, and salts thereof; one or more preservatives selected from chlorhexidine, sorbic acid, and salts thereof; one or more thickening ingredients selected from carboxymethyl cellulose, methyl cellulose, vinyl polymer compounds, and salts thereof; a polyol; one or more anti-inflammatory ingredients selected from berberine, azulenesulfonic acid, allantoin, zinc sulfate, and salts thereof; one or more antibacterial agents selected from sulfamethoxazole and its salts; and one or more cooling agents selected from eucalyptus oil and bergamot oil, thereby imparting to the aqueous composition an effect of suppressing weight change of a resin container containing polybutylene terephthalate.

[5]

A method for imparting an effect of inhibiting wetting of a resin container containing polybutylene terephthalate to an aqueous composition, wherein (B) a buffer and (A) at least one selected from the group consisting of polysaccharides; monosaccharides; vitamin _B12 , vitamin B2, and the like are coexisting in the aqueous composition. ₂ , vitamin A, and one or more panthenol; one or more oils selected from plant oils, animal oils, and mineral oils; one or more surfactants selected from polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, polyoxyethylene polyoxypropylene glycol, and polyoxyl stearate; one or more antiallergic ingredients selected from tranilast, ketotifen, diphenhydramine, and salts thereof; one or more preservatives selected from chlorhexidine, sorbic acid, and salts thereof; one or more thickening ingredients selected from carboxymethyl cellulose, methyl cellulose, vinyl polymers, and salts thereof; a polyol; one or more anti-inflammatory ingredients selected from berberine, azulenesulfonic acid, allantoin, zinc sulfate, and salts thereof; one or more antibacterial agents selected from sulfamethoxazole and its salts; and one or more cooling agents selected from eucalyptus oil and bergamot oil, thereby imparting to the aqueous composition an effect of inhibiting wetting of a resin container containing polybutylene terephthalate.

[6]

A liquid repellency improving agent for an ophthalmic resin container containing polybutylene terephthalate, comprising (B) a buffer and (A) at least one selected from the group consisting of polysaccharides; monosaccharides; vitamins _B12 , vitamin B2, ₂ , vitamin A, and one or more panthenol; one or more oils selected from plant oils, animal oils, and mineral oils; one or more surfactants selected from polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, polyoxyethylene polyoxypropylene glycol, and polyoxyl stearate; one or more antiallergic ingredients selected from tranilast, ketotifen, diphenhydramine, and salts thereof; one or more preservatives selected from chlorhexidine, sorbic acid, and salts thereof; one or more thickening ingredients selected from carboxymethyl cellulose, methyl cellulose, vinyl polymer compounds, and salts thereof; polyols; one or more anti-inflammatory ingredients selected from berberine, azulenesulfonic acid, allantoin, zinc sulfate, and salts thereof; one or more antibacterial agents selected from sulfamethoxazole and its salts; one or more cooling agents selected from eucalyptus oil and bergamot oil.

The ophthalmic aqueous composition, method for suppressing weight change, degradation, and wetting of a polybutylene terephthalate-containing resin container, lyophobicity-enhancing agent, and method and production method of the present invention can use the components and concentrations described below.

The ophthalmic aqueous composition of the present invention, when housed in a container containing PBT resin, can stabilize the container and suppress degradation of the container. Furthermore, it is expected to suppress wetting, improve liquid repellency, and reduce residual liquid in the container.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a graph showing changes in the weight of a PBT resin-containing sheet before and after the sheet is immersed in an ophthalmic aqueous composition and subjected to heat treatment.

DETAILED DESCRIPTION

In the present invention, the unit of content "w/v%" is synonymous with "g/100 mL". In the present invention, "amount blended" is synonymous with "content".

The inventors of the present invention have discovered that when ophthalmic aqueous compositions are stored in containers containing PBT resin, the PBT resin undergoes weight changes, resulting in reduced container strength, cracking, deformation, and decreased sealing properties. Specifically, when a container containing PBT resin is used to store a pharmaceutical agent such as an ophthalmic aqueous composition for a certain period of time, the problem of changes in the properties of the PBT resin container becomes more severe. The ophthalmic aqueous composition of the present invention can solve this problem.

The ophthalmic aqueous composition of the present invention comprises (B) a buffer and (A) at least one selected from the group consisting of polysaccharides; monosaccharides; vitamins _B12 , vitamin B2, One or more vitamins selected from the group consisting of vitamins ₂ , vitamin A, and panthenol; one or more oils selected from the group consisting of plant oils, animal oils, and mineral oils; one or more surfactants selected from the group consisting of polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, polyoxyethylene polyoxypropylene glycol, and polyoxyl stearate; one or more antiallergic ingredients selected from the group consisting of tranilast, ketotifen, diphenhydramine, and their salts; one or more preservatives selected from the group consisting of chlorhexidine, sorbic acid, and their salts; one or more thickening ingredients selected from the group consisting of carboxymethyl cellulose, methyl cellulose, vinyl polymers, and their salts; a polyol; one or more anti-inflammatory ingredients selected from the group consisting of berberine, azulenesulfonic acid, allantoin, zinc sulfate, and their salts; one or more antibacterial agents selected from the group consisting of sulfamethoxazole and its salts; and one or more cooling agents selected from the group consisting of eucalyptus oil and bergamot oil. The ophthalmic aqueous composition of the present invention is contained in a container containing PBT resin.

In the present invention, an aqueous composition refers to a composition containing water. The aqueous composition preferably contains 50 w/v% or more of water, more preferably 70 w/v% or more, further preferably 80 w/v% or more, even more preferably 85 w/v% or more, and particularly preferably 90 w/v% or more, relative to the total amount of the aqueous composition. In the present invention, an ophthalmic aqueous composition refers to any aqueous composition related to ophthalmology, such as eye drops (synonymous with eye drops or eye drops), eyewashes (synonymous with eyewashes or eyewashes), contact lens lubricants, contact lens cleaning solutions, contact lens preservatives, or contact lens disinfectants.

In the ophthalmic aqueous composition of the present invention, as component (A), at least one selected from the following substances can be used: polysaccharides; monosaccharides; vitamin _B12 ; vitamin B2; ₂ , vitamin A, and one or more panthenol; one or more oils selected from plant oils, animal oils, and mineral oils; one or more surfactants selected from polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, polyoxyethylene polyoxypropylene glycol, and polyoxyl stearate; one or more antiallergic ingredients selected from tranilast, ketotifen, diphenhydramine, and salts thereof; one or more preservatives selected from chlorhexidine, sorbic acid, and salts thereof; one or more thickening ingredients selected from carboxymethyl cellulose, methyl cellulose, vinyl polymer compounds, and salts thereof; polyols; one or more anti-inflammatory ingredients selected from berberine, azulenesulfonic acid, allantoin, zinc sulfate, and salts thereof; one or more antibacterial agents selected from sulfamethoxazole and its salts; one or more cooling agents selected from eucalyptus oil and bergamot oil.

In the present invention, these components (A) may be used alone or in combination of two or more. Components (A) may be naturally derived or chemically synthesized. Components (A) may also be any commercially available components.

In the present invention, the polysaccharide of component (A) is preferably an acidic polysaccharide. Acidic polysaccharides refer to polysaccharides containing a repeating structure of two or more monosaccharides and an acidic group. Here, the acidic group is not limited, but particularly refers to a carboxyl group or a sulfate group. The constituent components of the repeating structure are not limited, and examples include uronic acids such as glucuronic acid, iduronic acid, mannuronic acid, and guluronic acid, amino sugars such as galactosamine or glucosamine, galactose, mannose, glucose, and rhamnose.

Examples of such acidic polysaccharides include, but are not limited to, hyaluronic acid, chondroitin sulfate, dermatan sulfate, heparin, keratan sulfate, xanthan gum, gellan gum, alginic acid, and salts thereof.

As the acidic polysaccharide of component (A), components obtained from nature or chemically synthesized components can be used, and the source is not particularly limited. Commercially available products can also be used as acidic polysaccharides. Acidic polysaccharides can also use alkali metal salts of sodium, potassium, etc., alkaline earth metal salts of calcium, magnesium, etc., metal salts of iron, manganese, etc., and other physiologically or pharmaceutically acceptable salts. In addition, acetylated reactants can also be used. These acidic polysaccharides can be used alone or in combination of two or more. As the acidic polysaccharide of component (A), preferably chondroitin sulfate, hyaluronic acid, xanthan gum, gellan gum, alginic acid and their salts, particularly preferably sodium chondroitin sulfate, sodium hyaluronate, alginic acid, gellan gum.

The molecular weight of the acidic polysaccharide of component (A) varies depending on the number and type of repeating units and is not limited. The weight-average molecular weight can range from several hundred to several million. From the perspective of more significantly achieving the effects of the present invention, such as suppressing the degradation of PBT resin-containing containers, the weight-average molecular weight of the acidic polysaccharide of component (A) is preferably 1,000 to 5,000,000, and more preferably 5,000 to 3,000,000. More specifically, for example, the weight-average molecular weight of chondroitin sulfate or its salt is preferably 1,000 to 3,000,000, more preferably 5,000 to 1,500,000, and even more preferably 10,000 to 500,000. More specifically, for example, the weight-average molecular weight of hyaluronic acid or its salt is preferably 100,000 to 5,000,000, more preferably 500,000 to 4,000,000, and even more preferably 600,000 to 2,500,000.

In the present invention, the monosaccharides of component (A) include, in addition to aldoses such as glucose, ribose, glyceraldehyde, erythrose, threose, lyxose, xylose, arabinose, allose, talose, gulose, altrose, mannose, galactose, and idose, ketoses such as dihydroxyacetone, erythrulose, xylulose, ribulose, psicose, fructose, sorbose, and tagatose. Among these, glucose, galactose, mannose, fructose, and sorbose are preferred, with glucose being particularly preferred. These can be used alone or in combination of two or more. Commercially available monosaccharides can also be used as such monosaccharides.

In the present invention, the vitamins of component (A) may be fat-soluble vitamins or water-soluble vitamins. As fat-soluble vitamins, for example, they may be selected from retinol, retinyl acetate, retinyl palmitate, retinal, retinoic acid, methyl retinoate, ethyl retinoate, retinyl retinoate, vitamin A fatty acid esters, d-δ-tocopheryl retinoate, α-tocopheryl retinoate, β-tocopheryl retinoate, carotene, dehydroretinal, lycopene, and their salts, etc., and at least one of vitamin A. As water-soluble vitamins, for example, they may be selected from vitamin B2 such as riboflavin, flavin mononucleotide, flavin adenine dinucleotide, riboflavin butyrate, riboflavin tetrabutyrate, riboflavin 5'-sodium phosphate, riboflavin tetranicotinate, and their salts; vitamin _B12 such as cyanocobalamin, hydroxocobalamin, methylcobalamin, deoxyadenosylcobalamin, and their salts; and at least one of pantothenic acid.

The vitamins in component (A) are preferably at least one selected from cyanocobalamin, retinol, panthenol, flavin adenine dinucleotide, and salts thereof, and particularly preferably at least one selected from cyanocobalamin, retinyl palmitate, retinyl acetate, panthenol, and sodium flavin adenine dinucleotide. Examples of vitamin A include retinyl palmitate manufactured by DSM, of which 0.550 μg is equivalent to 1 I.U. of vitamin A. The term "I.U." refers to an international unit calculated using methods such as those described in the Sixteenth Revised Japanese Pharmacopoeia Vitamin A Quantitative Method.

These vitamins can be used alone or in combination of two or more. Any commercially available vitamins can be used as such vitamins.

In the present invention, the oil component (A) may be one or more oil components selected from vegetable oils, animal oils, and mineral oils. When an oil component is used as component (A), vegetable oils and/or mineral oils are more preferred from the viewpoint of more significantly achieving the effects of the present invention.

Here, the vegetable oil is not particularly limited as long as it is an oil made from plants. Preferably, it is a vegetable oil containing triglycerides. The vegetable oil of component (A) is not limited. Specifically, sesame oil, castor oil, soybean oil, peanut oil, almond oil, wheat germ oil, camellia oil, corn oil, rapeseed oil, sunflower oil, cottonseed oil, olive oil, or their derivatives can be mentioned. The vegetable oil as component (A) is preferably sesame oil, castor oil, soybean oil, or their derivatives, and is particularly preferably sesame oil and castor oil. These vegetable oils can be used alone or in combination of two or more. Commercially available products can also be used as such vegetable oils.

The animal oil of component (A) is not limited. Specifically, squalane, lanolin, tilapia oil, horse oil, whale oil, liver oil, mink oil, egg yolk oil, beef tallow, milk fat, lard, etc. can be mentioned. The animal oil of component (A) is preferably squalane, lanolin, egg yolk oil, or their derivatives, and is particularly preferably squalane and refined lanolin. Here, the animal oil is not particularly limited as long as it is an oil made from an animal. These animal oils can be used alone or in combination of two or more. Any commercially available animal oil can also be used.

The mineral oil of component (A) refers to a liquid or paste-like chemical substance obtained by refining hydrocarbon oil from natural petroleum. The mineral oil of component (A) is not limited. Specifically, paraffin oil, liquid paraffin, vaseline, etc. can be mentioned, and liquid paraffin, light liquid paraffin, and white vaseline are particularly preferred. These mineral oils can be used alone or in combination of two or more. Any commercially available product can also be used for this mineral oil. For example, Haikoru M-202 manufactured by Kaneda Co., Ltd. can be mentioned as liquid paraffin.

In the present invention, the surfactant of the component (A) may be one or more selected from polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, polyoxyethylene polyoxypropylene glycol, and polyoxyl stearate.

Specific examples of such surfactants include poloxamer 407, polyoxyethylene (200) polyoxypropylene (70) glycol, poloxamer 188, polyoxyethylene (120) polyoxypropylene (40) glycol, polyoxyethylene (54) polyoxypropylene (39) glycol, polyoxyethylene (20) polyoxypropylene (20) glycol, and polyoxyethylene polyoxypropylene glycols such as TETRONIC; polyoxyethylene hardened castor oil 5, polyoxyethylene hardened castor oil 10, polyoxyethylene hardened castor oil 20, polyoxyethylene hardened castor oil 40, polyoxyethylene hardened castor oil 50, polyoxyethylene hardened castor oil Polyoxyethylene hardened castor oils such as polyoxyethylene castor oil 60 and polyoxyethylene hardened castor oil 100; polyoxyethylene castor oil 3, polyoxyethylene castor oil 4, polyoxyethylene castor oil 6, polyoxyethylene castor oil 7, polyoxyethylene castor oil 10, polyoxyethylene castor oil 13.5, polyoxyethylene castor oil 17, polyoxyethylene castor oil 20, polyoxyethylene castor oil 25, polyoxyethylene castor oil 35, polyoxyethylene castor oil 40, polyoxyethylene castor oil 50, polyoxyethylene castor oil 60, etc.; polyoxyl stearate 40, polyoxyl stearate 140, etc.

Among the surfactants of component (A), preferred are poloxamer 407, polyoxyethylene (200) polyoxypropylene (70) glycol, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene hydrogenated castor oil 60, polyoxyethylene castor oil 3, polyoxyethylene castor oil 10, polyoxyethylene castor oil 35, polyoxyl stearate 40, and polyoxyl stearate 140; more preferred are poloxamer 407, polyoxyethylene hydrogenated castor oil 60, polyoxyethylene castor oil 10, polyoxyethylene castor oil 35, and polyoxyl stearate 40.

The average number of moles of ethylene oxide added to the polyoxyethylene castor oil used as the component (A) is not particularly limited, and may be, for example, 2 to 70 mol, preferably 2 to 60, more preferably 3 to 50, and particularly preferably 3 to 40. The average number of moles of ethylene oxide added to the polyoxyethylene polyoxypropylene glycol used as the component (A) is not particularly limited, and may be, for example, 10 to 350 mol, preferably 30 to 300, more preferably 50 to 300, and particularly preferably 100 to 250. The average number of moles of ethylene oxide added to the polyoxyethylene hydrogenated castor oil used as the component (A) is not particularly limited, and may be 3 to 120 mol, preferably 20 to 100, and further preferably 30 to 80. The average number of moles of ethylene oxide added to the polyoxyl stearate used as the component (A) is not particularly limited, but may be 3 to 200 mol, preferably 20 to 180, and more preferably 30 to 160.

In the present invention, component (A) may be one or more antiallergic ingredients selected from tranilast, ketotifen, diphenhydramine, and salts thereof. Among the antiallergic ingredients, tranilast, ketotifen fumarate, and diphenhydramine hydrochloride are preferred.

In the present invention, component (A) may be one or more preservatives selected from chlorhexidine, sorbic acid, and salts thereof. Among the preservatives, chlorhexidine gluconate, sorbic acid, and potassium sorbate are preferred.

In the present invention, the thickening component of component (A) may be a cellulose-based polymer compound or a vinyl-based polymer compound. The cellulose-based polymer compound is not particularly limited, and examples thereof include carboxymethyl cellulose, methyl cellulose, and salts thereof. The vinyl-based polymer compound is not particularly limited, and examples thereof include polyvinyl pyrrolidone, polyvinyl alcohol (completely or partially saponified), carboxyvinyl polymers, and salts thereof. The thickening component of component (A) is preferably carboxymethyl cellulose, methyl cellulose, a vinyl polymer compound, and a salt thereof, more preferably carboxymethyl cellulose, sodium carboxymethyl cellulose, methyl cellulose, polyvinyl pyrrolidone, and a carboxyvinyl polymer, further preferably carboxymethyl cellulose, sodium carboxymethyl cellulose, methyl cellulose, polyvinyl pyrrolidone K17, polyvinyl pyrrolidone K25, polyvinyl pyrrolidone K30, polyvinyl pyrrolidone K90, and a carboxyvinyl polymer, and particularly preferably carboxymethyl cellulose, sodium carboxymethyl cellulose, methyl cellulose, polyvinyl pyrrolidone K25, polyvinyl pyrrolidone K30, polyvinyl pyrrolidone K90, and a carboxyvinyl polymer.

In the present invention, component (A) may be a polyol. The polyol is not limited, but is preferably one or more polyols selected from propylene glycol, glycerin, and mannitol.

In the present invention, component (A) may be one or more anti-inflammatory ingredients selected from berberine, azulenesulfonic acid, allantoin, zinc sulfate, or salts thereof. Among the anti-inflammatory ingredients, berberine sulfate, berberine chloride, sodium azulenesulfonate, allantoin, and zinc sulfate are preferred.

In the present invention, component (A) may be one or more antibacterial agents selected from sulfamethoxazole or its salts. Here, the salt of sulfamethoxazole is preferably sulfamethoxazole sodium.

In the present invention, component (A) may be one or more cooling agents selected from eucalyptus oil and bergamot oil.

All of these (A) components can be used alone or in any combination of two or more. It is particularly preferred to combine two or more. In the case of two or more, for example, it can be set to two or more different substances of the same classification, or it can be set to two or more different substances of different classifications. For example, it is also possible to contain two or more polysaccharides, or to select one or more from the polysaccharides and one or more from the vitamins and combine them. The same is true for (A) components such as monosaccharides, oils, surfactants, antiallergic ingredients, preservatives, thickening ingredients, polyols, anti-inflammatory ingredients, antibacterial agents, and cooling agents.

In the ophthalmic aqueous composition of the present invention, the total content of component (A) relative to the total amount of the ophthalmic aqueous composition can be appropriately adjusted based on the type of component (A) and the types and contents of other ingredients in order to more significantly achieve the effects of the present invention. The total content of component (A) relative to the total amount of the ophthalmic aqueous composition is preferably 0.0001 w/v% or more, more preferably 0.001 w/v% or more, more preferably 0.005 w/v% or more, and even more preferably 0.01 w/v% or more. The total content of component (A) relative to the total amount of the ophthalmic aqueous composition is preferably 20 w/v% or less, more preferably 10 w/v% or less, even more preferably 5 w/v% or less, even more preferably 3 w/v% or less, and most preferably 1 w/v% or less.

The total content of the polysaccharide of the present invention relative to the total amount of the ophthalmic aqueous composition can be appropriately set depending on the type of component (A) and the types and contents of other ingredients. From the viewpoint of more significantly achieving the effects of the present invention, the total content of the polysaccharide is preferably 0.0001 to 6 w/v%, more preferably 0.0005 to 4 w/v%, and particularly preferably 0.001 to 2 w/v%, relative to the total amount of the ophthalmic aqueous composition.

Although not limited to this, in a preferred embodiment, for example, when chondroitin sulfate or a salt thereof is contained as component (A), the content of chondroitin sulfate or a salt thereof alone is preferably 0.0001 to 5 w/v% of the total amount of the ophthalmic aqueous composition, and more preferably 0.005 to 3 w/v%. Similarly, in another preferred embodiment, for example, when hyaluronic acid or a salt thereof is contained as component (A), the content of hyaluronic acid or a salt thereof alone is preferably 0.0001 to 1 w/v% of the total amount of the ophthalmic aqueous composition, and more preferably 0.0005 to 0.5 w/v%.

The total content of the monosaccharides in the present invention relative to the total amount of the ophthalmic aqueous composition can be appropriately set depending on the type of component (A) and the types and contents of other ingredients. From the perspective of more significantly achieving the effects of the present invention, the total content of the monosaccharides is preferably 0.0001 to 3 w/v%, more preferably 0.005 to 1.5 w/v%, and particularly preferably 0.001 to 0.5 w/v%, relative to the total amount of the ophthalmic aqueous composition.

In another preferred embodiment, when glucose is contained as component (A), the content of glucose alone is preferably 0.0001 w/v% to 3 w/v% of the total amount of the ophthalmic aqueous composition, more preferably 0.005 w/v% to 1.5 w/v%, and particularly preferably 0.001 w/v% to 0.5 w/v%.

The total content of the vitamins in the present invention relative to the total amount of the ophthalmic aqueous composition can be appropriately set depending on the type of component (A) and the types and contents of other ingredients. From the perspective of more significantly achieving the effects of the present invention, the total content of the vitamins relative to the total amount of the ophthalmic aqueous composition is preferably 0.00001 to 1.6 w/v%, more preferably 0.0005 to 0.8 w/v%, and particularly preferably 0.0005 to 0.4 w/v%.

While not limited to this, in a preferred embodiment, for example, when retinyl palmitate is included as component (A), the content of retinyl palmitate alone is preferably 10 to 500,000 units/100 mL, more preferably 100 to 300,000 units/100 mL, and even more preferably 500 to 200,000 units/100 mL, based on the total amount of the ophthalmic aqueous composition. The content also depends on the units of retinyl palmitate added, but is preferably 0.005 to 0.5 W/V%, more preferably 0.001 to 0.4 W/V%, and even more preferably 0.01 to 0.3 W/V%. Similarly, in other preferred embodiments, for example, cyanocobalamin is used as the sole component (A), and is preferably contained in an amount of 0.00001 to 1 w/v% of the total amount of the ophthalmic aqueous composition, more preferably 0.00005 to 0.5 w/v%, and particularly preferably 0.0001 to 0.02 w/v%.

The total content of the oil component of the present invention relative to the total amount of the ophthalmic aqueous composition can be appropriately set depending on the type of component (A) and the types and contents of other ingredients. From the perspective of more significantly achieving the effects of the present invention, the total content of the oil component is preferably 0.00001 to 6 w/v%, more preferably 0.0005 to 3 w/v%, and particularly preferably 0.0001 to 1 w/v%, relative to the total amount of the ophthalmic aqueous composition.

Although not limited to these, in a preferred embodiment, for example, when sesame oil is included as component (A), the content of sesame oil alone is preferably 0.00001 to 5 w/v% of the total amount of the ophthalmic aqueous composition, and more preferably 0.0001 to 1 w/v%. Similarly, in another preferred embodiment, for example, when castor oil is included as component (A), the content of castor oil alone is preferably 0.00001 to 5 w/v% of the total amount of the ophthalmic aqueous composition, and more preferably 0.0001 to 1 w/v%. Similarly, in another preferred embodiment, for example, when liquid paraffin is included as component (A), the content of liquid paraffin alone is preferably 0.00001 to 2 w/v% of the total amount of the ophthalmic aqueous composition, and more preferably 0.0001 to 1 w/v%. Similarly, in another preferred embodiment, for example, when vaseline is contained as component (A), the content of vaseline alone is preferably 0.00001 w/v% to 5 w/v%, and more preferably 0.00005 w/v% to 1 w/v% of the total amount of the ophthalmic aqueous composition.

The total content of the surfactants of the present invention relative to the total amount of the ophthalmic aqueous composition can be appropriately set depending on the type of component (A) and the types and contents of other ingredients. From the perspective of more significantly achieving the effects of the present invention, the total content of the surfactants is preferably 0.00001 to 10 w/v%, more preferably 0.0001 to 8 w/v%, and particularly preferably 0.001 to 5 w/v%, relative to the total amount of the ophthalmic aqueous composition.

Although not limited to this, in a preferred embodiment, for example, when polyoxyethylene polyoxypropylene glycol is included as component (A), the content of the polyoxyethylene polyoxypropylene glycol alone is preferably 0.00001 to 10 w/v% of the total amount of the ophthalmic aqueous composition, more preferably 0.0001 to 8 w/v%, and particularly preferably 0.001 to 5 w/v%. Similarly, in another preferred embodiment, for example, when polyoxyethylene castor oil is included as component (A), the content of the polyoxyethylene castor oil alone is preferably 0.00001 to 10 w/v% of the total amount of the ophthalmic aqueous composition, more preferably 0.0001 to 5 w/v%, and particularly preferably 0.001 to 3 w/v%.

The total content of the antiallergic component relative to the total amount of the ophthalmic aqueous composition of the present invention is preferably 0.00001 w/v% to 5 w/v%, more preferably 0.0005 w/v% to 1 w/v%, and particularly preferably 0.0005 w/v% to 0.5 w/v%, relative to the total amount of the ophthalmic aqueous composition, from the viewpoint of more significantly achieving the effects of the present invention.

The total content of the preservative relative to the total amount of the ophthalmic aqueous composition of the present invention is preferably 0.00001 w/v% to 2 w/v%, more preferably 0.00005 w/v% to 1 w/v%, and particularly preferably 0.0001 w/v% to 0.5 w/v%, relative to the total amount of the ophthalmic aqueous composition, from the viewpoint of more significantly achieving the effects of the present invention.

The total content of the thickening component relative to the total amount of the ophthalmic aqueous composition of the present invention is preferably 0.0001 w/v% to 10 w/v%, more preferably 0.0005 w/v% to 8 w/v%, and particularly preferably 0.001 w/v% to 5 w/v%, relative to the total amount of the ophthalmic aqueous composition, from the viewpoint of more significantly achieving the effects of the present invention.

The total content of the polyol relative to the total amount of the ophthalmic aqueous composition of the present invention is preferably 0.00005 w/v% to 10 w/v%, more preferably 0.0001 w/v% to 8 w/v%, and particularly preferably 0.005 w/v% to 5 w/v%, relative to the total amount of the ophthalmic aqueous composition, from the viewpoint of more significantly achieving the effects of the present invention.

The total content of the anti-inflammatory component relative to the total amount of the ophthalmic aqueous composition of the present invention is preferably 0.00001 w/v% to 3 w/v%, more preferably 0.00005 w/v% to 1.5 w/v%, and particularly preferably 0.0001 w/v% to 0.6 w/v%, relative to the total amount of the ophthalmic aqueous composition, from the viewpoint of more significantly achieving the effects of the present invention.

The total content of the antibacterial component relative to the total amount of the ophthalmic aqueous composition of the present invention is preferably 0.01 w/v% to 6 w/v%, more preferably 0.05 w/v% to 5 w/v%, and particularly preferably 0.4 w/v% to 4 w/v% relative to the total amount of the ophthalmic aqueous composition, from the viewpoint of more significantly achieving the effects of the present invention.

The total content of the cooling agent relative to the total amount of the ophthalmic aqueous composition of the present invention is preferably 0.0001 w/v% to 1 w/v%, more preferably 0.0005 w/v% to 0.5 w/v%, and particularly preferably 0.001 w/v% to 0.1 w/v%, relative to the total amount of the ophthalmic aqueous composition, from the viewpoint of more significantly achieving the effects of the present invention.

In the present invention, the buffer of the component (B) may be an inorganic buffer or an organic buffer.

The inorganic buffering agent of component (B) of the present invention is preferably boric acid or a salt of boric acid. The salt of boric acid is not particularly limited as long as it is a physiologically or pharmaceutically acceptable salt. Examples include alkali metal salts, alkaline earth metal salts, and salts of boric acid with organic bases. More specifically, examples include sodium, potassium, calcium, magnesium, ammonium, or salts of boric acid with diethanolamine, ethylenediamine, etc. Preferred examples of borates are not limited, and specifically include borax, sodium borate, ammonium borate, potassium tetraborate, etc. Among them, borax is particularly preferably used.

The organic buffer of component (B) of the present invention is preferably ε-aminocaproic acid, phosphoric acid, citric acid, carbonic acid, or 2-amino-2-hydroxymethyl-1,3-propanediol (tris, tromethamine, trishydroxymethylaminomethane), or a salt thereof. There is no particular limitation on their salts as long as they are physiologically or pharmaceutically acceptable salts. Examples include alkali metal salts, alkaline earth metal salts, and salts of organic bases of ε-aminocaproic acid, phosphoric acid, citric acid, carbonic acid, or 2-amino-2-hydroxymethyl-1,3-propanediol. Preferred examples include sodium, potassium, calcium, magnesium, ammonium, or salts with diethanolamine, ethylenediamine, etc.

In the present invention, these components (B) may be used alone or in combination of two or more. Components (B) may be naturally derived or chemically synthesized. Components (B) may also be any commercially available products.

In the ophthalmic aqueous composition of the present invention, from the viewpoint of more significantly achieving the effects of the present invention, the total content of component (B) is preferably 0.001 w/v% or more, more preferably 0.01 w/v% or more, and even more preferably 0.1 w/v% or more, relative to the total amount of the ophthalmic aqueous composition. Furthermore, the total content of component (B) is preferably 20 w/v% or less, more preferably 15 w/v% or less, even more preferably 10 w/v% or less, even more preferably 5 w/v% or less, and most preferably 3 w/v% or less, relative to the total amount of the ophthalmic aqueous composition.

Although not limited, in a preferred embodiment, for example, when ε-aminocaproic acid or 2-amino-2-hydroxymethyl-1,3-propanediol is contained as component (B), the content of ε-aminocaproic acid or 2-amino-2-hydroxymethyl-1,3-propanediol alone is preferably 0.001 to 6 w/v% of the total amount of the ophthalmic aqueous composition, more preferably 0.01 to 8 w/v%, and particularly preferably 0.05 to 5 w/v%. Similarly, in another preferred embodiment, for example, when boric acid, phosphoric acid, citric acid, carbonic acid, and salts thereof are contained as component (B), the content of boric acid, phosphoric acid, citric acid, carbonic acid, and salts thereof alone is preferably 0.001 to 5 w/v% of the total amount of the ophthalmic aqueous composition, more preferably 0.005 to 4 w/v%, and particularly preferably 0.01 to 3 w/v%.

In the ophthalmic aqueous composition of the present invention, from the viewpoint of more significantly achieving the effects of the present invention, the total content of component (B) is preferably 0.00001 to 10,000 parts by weight, more preferably 0.0001 to 5,000 parts by weight, even more preferably 0.0005 to 3,000 parts by weight, particularly preferably 0.001 to 2,000 parts by weight, and most preferably 0.01 to 1,000 parts by weight, per 1 part by weight of the total content of component (A).

In the ophthalmic aqueous composition of the present invention, the combination of component (A) and component (B) is not particularly limited and can be appropriately set depending on the types of components (A) and (B), etc. Examples of the combination are shown in the following two-page Table 1.

[Table 1]

In the present invention, a container containing PBT resin refers to an ophthalmic container, and a portion or the entire container refers to a container molded with a resin containing polybutylene terephthalate. Here, "a portion of the container" refers to at least a portion of the portion that contacts the ophthalmic aqueous composition contained therein. The portion that contacts the ophthalmic aqueous composition may be the innermost layer of a multilayer structure formed by an inner plug, an open-hole inner plug, and the inner surface of the container. For example, in a container with an open-hole inner plug (nozzle), only the inner plug portion may be formed from a PBT resin. Alternatively, the receiving portion other than the inner plug may also be formed from a PBT resin. Alternatively, the entire container may be molded from a PBT resin. At least a portion of the surface in contact with the ophthalmic aqueous composition may be formed from a PBT resin, and the entire contact surface is most preferably formed from a PBT resin. When a portion of the container is formed of a PBT resin, there is no particular limitation on the type of resin forming the other portion, and the container may contain at least one polymer selected from polyethylene terephthalate (PET), polystyrene (PS), acrylonitrile butadiene styrene (ABS), polycarbonate, polyethylene (PE), polypropylene (PP), polymethyl methacrylate, ethylene vinyl acetate copolymer, and ethylene vinyl alcohol copolymer as a constituent component.

In the present invention, the shape and internal volume of the PBT resin container are not particularly limited. For example, as long as the container is used for conventional eye drops or contact lens lubricants, the container can accommodate a volume of 0.1 ml to 50 ml, preferably 2 ml to 40 ml, and more preferably 4 ml to 25 ml. As long as the container is used for eyewash or contact lens care solutions, the PBT resin container can have an internal volume of 40 ml to 600 ml.

Furthermore, the PBT resin-containing container of the present invention may be a container capable of storing an ophthalmic aqueous composition to be applied to contact lenses.

The ophthalmic aqueous composition used in the present invention may be in a multi-dose form containing a dose for multiple uses or in a single-dose form containing a dose for a single use.

In the present invention, containers containing PBT resin are particularly preferably eye drop containers, eyewash containers, contact lens lubricating solution containers, contact lens care solution containers (including contact lens cleaning solution containers, contact lens preservative solution containers, contact lens disinfectant solution containers, contact lens multi-purpose solution containers, etc.), and contact lens packaging solution containers. Eye drop containers, contact lens lubricating solution containers, and contact lens care solution containers are particularly preferred. It should be noted that the term "contact lenses" herein refers to all contact lenses, and can be both soft and hard contact lenses.

The present invention also provides a product comprising an ophthalmic aqueous composition contained in a PBT resin container. The present invention also provides an eye drop, an eye wash, or a contact lens application product containing a container containing the ophthalmic aqueous composition.

The PBT resin in the PBT resin-containing container of the present invention comprises a polymer obtained by a known polymerization method such as polycondensation of terephthalic acid or its ester-forming derivative with 1,4-butanediol. A PBT-containing resin can also be prepared by adding additives such as a stabilizer to such a polymer. Commercially available PBT-containing resins can be used without particular limitation. Examples include "Novaduran (registered trademark) 5010R5" manufactured by Mitsubishi Engineering-Plastics Corporation. The polymer synthesized by polycondensation of terephthalic acid or its ester-forming derivative with 1,4-butanediol may contain any other monomer as a constituent component, and further, may contain other polymers. Examples of such other polymers include, but are not limited to, polycarbonate, (meth)acrylic polymers, polystyrene (PS), polyethylene naphthalate (PEN), polyethylene terephthalate (PET), polyethylene (PE), polyarylate, and polypropylene (PP). Although not limited here, examples of ester-forming derivatives of terephthalic acid include dimethyl terephthalate. In the PBT-containing resin of the present invention, the polymer synthesized by polycondensation of terephthalic acid or its ester-forming derivative with 1,4-butanediol preferably accounts for 50% by weight or more of the polymer components constituting the resin, more preferably 60% by weight or more, and even more preferably 70% by weight or more. Commercially available products may also be used.

The PBT-containing resin of the present invention also includes a resin further reinforced by containing a reinforcing agent such as glass fiber.

The ophthalmic aqueous composition of the present invention preferably contains, in addition to component (A) and component (B), other components commonly used in ophthalmic aqueous compositions. While these components are not particularly limited, sodium edetate is particularly preferred from the perspective of more significantly achieving the effects of the present invention. In the present invention, commercially available sodium edetate may also be used.

In the ophthalmic aqueous composition of the present invention, from the viewpoint of more significantly achieving the effects of the present invention, the total content of sodium edetate is preferably 0.0001 w/v% or more, more preferably 0.0005 w/v% or more, and even more preferably 0.001 w/v% or more, relative to the total amount of the ophthalmic aqueous composition. The total content of sodium edetate is preferably 1 w/v% or less, more preferably 0.5 w/v% or less, and even more preferably 0.2 w/v% or less, relative to the total amount of the ophthalmic aqueous composition. Regarding the ratio of the content of sodium edetate relative to component (A), the total content of sodium edetate is preferably 0.0001 to 1000 parts by weight, more preferably 0.0005 to 500 parts by weight, and even more preferably 0.001 to 200 parts by weight, relative to 1 part by weight of the total content of component (A).

For example, active ingredients in ophthalmic drugs listed in the 2012 edition of the Non-prescription Drug Manufacturing (Import) Approval Standards (supervised by the Japan Society of Regulatory Science) can be exemplified. Specific examples include the following ingredients.

Antihistamine: Chlorpheniramine maleate

Antiallergic agents: Azalast, Amlexanox, Ibudilast, Levocabastine Hydrochloride, Sodium Cromolyn, Pemirolast Potassium, Olopatadine Hydrochloride, etc.

Decongestants: tetrahydrozoline hydrochloride, naphazoline hydrochloride, naphazoline nitrate, epinephrine, epinephrine hydrochloride, ephedrine hydrochloride, phenylephrine hydrochloride, methylephedrine hydrochloride, etc.

Amino acids: potassium aspartate, magnesium aspartate, aminoethylsulfonic acid, etc.

Anti-inflammatory agents: dipotassium glycyrrhizate, lysozyme chloride, pranoprofen, bromfenac, ketorolac tromethamine, nepafenac, etc.

Astringents: zinc white, zinc lactate, etc.

Others: sulfamethoxazole, sulfamethoxazole sodium, neostigmine methylsulfate, cinchocaine, etc.

Furthermore, the ophthalmic aqueous composition of the present invention may also contain additives such as carriers, thickeners, pH adjusters, general sugars, general tonicity agents, fragrances, cooling agents, and chelating agents, and at least one of these additives may be selected and incorporated in appropriate amounts. Examples of these additives include the various additives listed in the 2007 Dictionary of Pharmaceutical Additives (compiled by the Japan Pharmaceutical Additives Association). Representative ingredients include the following additives.

Carrier: aqueous carriers such as water and hydrous ethanol.

Thickeners: hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, etc.

Sugar alcohols: xylitol, sorbitol, etc. They can be any of the d-isomer, l-isomer or dl-isomer.

Tonicity agents: aminoethylsulfonic acid, polyethylene glycol, sodium bisulfite, sodium sulfite, potassium chloride, calcium chloride, sodium chloride, magnesium chloride, etc.

pH adjusters: hydrochloric acid, acetic acid, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, triethanolamine, monoethanolamine, diisopropanolamine, etc.

Stabilizers: butylated hydroxytoluene, sodium formaldehyde sulfoxylate (rongalite), sodium bisulfite, sodium metabisulfite, monoethanolamine, aluminum monostearate, glycerol monostearate, cyclodextrin, dextran, etc.

Chelating agents: succinic acid, trishydroxymethylaminomethane, nitrilotriacetic acid, 1-hydroxyethane-1,1-diphosphonic acid, polyphosphoric acid, metaphosphoric acid, hexametaphosphoric acid, etc.

Flavoring or cooling agents: menthol, camphor, borneol, geraniol, eucalyptol, citronellol, carvone, anethole, eugenol, eucalyptol, limonene, linalyl acetate, borneol, menthone, etc. These may be in the d-isomer, l-isomer, or dl-isomer form. Essential oils (peppermint oil, menthol oil, spearmint oil, peppermint oil, anise oil, cinnamon oil, rose oil, etc.) may also be incorporated.

Preservatives other than chlorhexidine, sorbic acid, and salts thereof: butylated hydroxytoluene, butylated hydroxyanisole, alkyldiaminoethylglycine hydrochloride, sodium benzoate, ethanol, tyloxapol, benzalkonium chloride, benzethonium chloride, zinc chloride, chlorobutanol, sodium dehydroacetate, methylparaben, ethylparaben, propylparaben, butylparaben, hydroxyquinoline sulfate, phenylethyl alcohol, benzyl alcohol, biguanide compounds (specifically, polyhexanide hydrochloride (polyhexamethylene biguanide) etc.), polychloridonium chloride, chlorocresol, p-chloro-m-xylenol, Groot (trade name of Rhodia Corporation), etc.

The water used in the ophthalmic aqueous composition of the present invention may be any water that is physiologically or pharmaceutically acceptable. Examples of such water include distilled water, ordinary water, purified water, sterile purified water, water for injection, and distilled water for injection. These definitions are based on the Sixteenth Revised Japanese Pharmacopoeia.

In the present invention, "salts" include basic salts such as salts of alkali metals, alkaline earth metals, and inorganic bases, and salts of organic bases, including salts of sodium, potassium, calcium, magnesium, and ammonium, or salts with diethanolamine, ethylenediamine, and the like. These salts can be obtained, for example, by converting sulfate groups or carboxyl groups present in liranabate, etc., into salts using known methods. Further examples include salts of amines such as ammonia, methylamine, dimethylamine, trimethylamine, dicyclohexylamine, tris(hydroxymethyl)aminomethane, N,N-bis(hydroxyethyl)piperazine, 2-amino-2-methyl-1-propanol, ethanolamine, N-methylglucamine, and L-glucamine; or salts with basic amino acids such as lysine, δ-hydroxylysine, and arginine. In addition, in the present invention, the "salt" includes acidic salts, for example, salts with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid; salts with organic acids such as methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, acetic acid, propionic acid, tartaric acid, fumaric acid, maleic acid, malic acid, oxalic acid, succinic acid, citric acid, benzoic acid, mandelic acid, cinnamic acid, lactic acid, glycolic acid, glucuronic acid, ascorbic acid, nicotinic acid, salicylic acid, gluconic acid, palmitic acid; or salts with acidic amino acids such as aspartic acid and glutamic acid.

The "physiologically or pharmaceutically acceptable salt" referred to in the present invention may also include solvates or hydrates of the salt.

The ophthalmic aqueous composition of the present invention may be in any form as long as it contains water, and may be, for example, in the form of an aqueous solution, a gel, a suspension, or an emulsion, but is preferably in the form of an aqueous solution.

The ophthalmic aqueous composition of the present invention may preferably have the following composition, but is not limited thereto. An ophthalmic aqueous composition containing sodium hyaluronate, boric acid, and water; an ophthalmic aqueous composition containing sodium hyaluronate, ε-aminocaproic acid, and water; an ophthalmic aqueous composition containing sodium hyaluronate, sodium hydrogen phosphate, and water; an ophthalmic aqueous composition containing sodium hyaluronate, sodium citrate, and water; an ophthalmic aqueous composition containing sodium hyaluronate, sodium hydrogen carbonate, and water; an ophthalmic aqueous composition containing sodium hyaluronate, 2-amino-2-hydroxymethyl-1,3-propanediol, and water; an ophthalmic aqueous composition containing sodium chondroitin sulfate, boric acid, and water; an ophthalmic aqueous composition containing sodium chondroitin sulfate, ε-aminocaproic acid, and water; an ophthalmic aqueous composition containing sodium chondroitin sulfate, sodium hydrogen phosphate, and water; an ophthalmic aqueous composition containing An ophthalmic aqueous composition comprising sodium chondroitin sulfate, sodium citrate, and water; an ophthalmic aqueous composition comprising sodium chondroitin sulfate, sodium bicarbonate, and water; an ophthalmic aqueous composition comprising sodium chondroitin sulfate, 2-amino-2-hydroxymethyl-1,3-propanediol, and water; an ophthalmic aqueous composition comprising glucose, boric acid, and water; an ophthalmic aqueous composition comprising glucose, ε-aminocaproic acid, and water; an ophthalmic aqueous composition comprising glucose, sodium hydrogen phosphate, and water; an ophthalmic aqueous composition comprising glucose, sodium citrate, and water; an ophthalmic aqueous composition comprising glucose, sodium bicarbonate, and water; and an ophthalmic aqueous composition comprising glucose, 2-amino-2-hydroxymethyl-1,3-propanediol, and water.

The pH of the ophthalmic aqueous composition of the present invention is not limited as long as it is within a physiologically or pharmaceutically acceptable range. For example, the pH is 3 or higher, preferably 4 or higher, more preferably 5 or higher, even more preferably 5.5 or higher, and even more preferably 6 or higher. The pH is 9 or lower, preferably 8.5 or lower, more preferably 8 or lower, even more preferably 7.5 or lower, and even more preferably 7 or lower.

The osmotic pressure ratio of the ophthalmic aqueous composition of the present invention can be appropriately set according to the types and contents of the ingredients, the application of the ophthalmic aqueous composition, the formulation form, and the method of use, as long as it is within the physiologically or pharmaceutically acceptable range. For example, it can be set to 0.4 to 5, preferably 0.5 to 4, more preferably 0.6 to 3, and even more preferably 0.7 to 2. In the ophthalmic aqueous composition of the present invention, the osmotic pressure ratio is determined as the osmotic pressure ratio to physiological saline based on the osmotic pressure measurement method (osmolarity measurement method) of the Sixteenth Revised Japanese Pharmacopoeia.

The viscosity of the ophthalmic aqueous composition of the present invention can be appropriately adjusted, as long as it is within a physiologically or pharmaceutically acceptable range, depending on the types and contents of the ingredients, the intended use of the ophthalmic aqueous composition, the formulation form, and the method of use. The viscosity at 20°C, as measured using a rotational viscometer (RE550 viscometer, manufactured by Tosangyo Co., Ltd., rotor; 1°34" x R24), is preferably 0.01 to 10,000 mPa·s, and more preferably 0.05 to 8,000 mPa·s.

The method of using the ophthalmic aqueous composition of the present invention can be appropriately determined according to the types and contents of the ingredients, the intended use of the ophthalmic aqueous composition, and the formulation form.

The ophthalmic aqueous composition of the present invention can also suppress the deterioration of containers containing PBT resins, and thus can be used as a deterioration inhibitor for containers containing PBT resins.

While not limiting, suppressing degradation of a PBT resin-containing container means that, after containing an ophthalmic aqueous composition, the container exhibits minimal changes in properties, even after use or storage for a certain period. For example, this refers to minimal weight change. From the perspective of suppressing degradation, the more weight change is suppressed, the better. When storing an ophthalmic aqueous composition in a PBT resin-containing container, problems arise, such as weight changes in the PBT resin, which can lead to decreased container strength, cracking, deformation, and reduced sealing properties. Specifically, when a PBT resin-containing container is used while storing a pharmaceutical agent, such as an ophthalmic aqueous composition, for a certain period, the problem of property changes in the PBT resin-containing container becomes more serious.

The ophthalmic aqueous composition of the present invention can also improve the liquid repellency of a container containing a PBT resin and suppress liquid residue in the container, and therefore can be used as a liquid repellency-enhancing agent for a container containing a PBT resin.

While not limited to the lyophobicity-enhancing agent for PBT resin containers, it encompasses situations where the ophthalmic aqueous composition has difficulty wetting the container. Thus, an indicator of the difficulty wetting the container with the ophthalmic aqueous composition can be, for example, the magnitude of the advancing contact angle, which is a dynamic contact angle. A larger advancing contact angle indicates less wetting and better lyophobicity. A smaller advancing contact angle or a larger negative value indicates easier wetting and poorer lyophobicity.

The ophthalmic aqueous composition of the present invention is provided individually or in a set in a container containing a PBT resin. By storing the ophthalmic aqueous composition of the present invention therein, the PBT resin container can be well maintained, and as a result, the properties of the ophthalmic aqueous composition are well maintained even after long-term storage.

The ophthalmic aqueous composition of the present invention is prepared by adding the aforementioned components (A) and (B), and optionally other components, to a carrier using a known production method so that the desired contents are achieved. For example, the composition can be produced using the methods described in the Sixteenth Revised Japanese Pharmacopoeia, General Rules for Preparations. Specifically, the composition can be prepared by dissolving or suspending the aforementioned components in pure water, adjusting the pH and osmotic pressure to a predetermined value, and sterilizing the composition using a known sterilization method.

Example

Next, the present invention will be specifically described with reference to Examples, but the present invention is not limited to the following Examples.

<Evaluation of Weight Change 1>

(Example 1)

Sodium hyaluronate (weight-average molecular weight 850,000 to 1,600,000) as component (A) and boric acid and borax as components (B) were dissolved in pure water at approximately 70°C to give the concentrations shown in Table 2, respectively, to prepare ophthalmic aqueous compositions. The pH was measured at room temperature using a HORIBA pH meter.

(Examples 2-3)

In the same manner as in Example 1, ophthalmic aqueous compositions of Examples 2 and 3 shown in Table 2 were prepared.

(Comparative Examples 1 to 3)

In the same manner as in Example 1, ophthalmic aqueous compositions of Comparative Examples 1 to 3 shown in Table 2 were prepared.

[Table 2]

(Test method)

3 mL of each test solution of Examples 1 to 3 and Comparative Examples 1 to 3 was filled into a 10 mL transparent glass vial (with a septum cap), and then one piece of PBT resin (product name: PBT Natural, manufactured by Alam Co.) with a diameter of about 1.0 cm, a weight of about 205 mg, and a thickness of about 2.0 mm was impregnated, and the vials were quickly sealed. After heat treatment at 70°C in a thermostatic bath for 2 weeks, the weight of each resin was measured, and the weight change per unit volume was calculated according to Formula 1. This heat treatment is equivalent to storage at room temperature for about 3 years. It can also be evaluated by the weight change relative to the initial weight. The volume of the PBT resin can also be calculated from the density and weight of the resin.

(Formula 1) Weight change per unit volume (mg/cm ³ ) =

(Weight of resin sheet after heat treatment - weight of resin sheet before heat treatment) / resin volume

The results of the tests conducted in this manner are shown in the lower column of Table 2.

Furthermore, the results are shown in a graph as shown in FIG1 .

As shown in Table 2 and Figure 1, in Comparative Example 1, where the PBT resin-containing sheet was immersed in pure water, an increase in weight was observed compared to before heat treatment. However, in Comparative Examples 2 and 3, which contained sodium hyaluronate as an acidic polysaccharide and glucose as a monosaccharide, the weight increase of the PBT resin-containing sheet was confirmed to be greater than that observed with pure water. However, in Examples 1-3, where boric acid and borax were added, the weight change per unit volume of the PBT resin was suppressed compared to the case of pure water alone (Comparative Example 1). This confirms that boric acid and borax suppress the weight change of the PBT resin-containing sheet caused by an ophthalmic aqueous composition containing one or more selected from acidic polysaccharides and monosaccharides, and inhibits the associated deterioration of the PBT resin. The mechanism of action is unclear, but it is believed that the hydrogen ions in the ophthalmic aqueous composition may have some effect on the chain molecular structure of the PBT resin through the buffering capacity of component (B).

<Evaluation of Weight Change 2>

(Examples 4 to 10)

The ophthalmic aqueous compositions shown in Tables 3 to 6 were prepared. The pH thereof was measured at room temperature using a HORIBA pH meter.

(Comparative Examples 4 to 12)

In the same manner as in Examples 4 to 10, ophthalmic aqueous compositions of Comparative Examples 4 to 12 shown in Tables 3 to 6 were prepared.

[Table 3]

[Table 4]

[Table 5]

[Table 6]

(Test method)

3 mL of each test solution from Examples 4 to 10 and Comparative Examples 4 to 12 was filled into a 10 mL transparent glass vial (with a septum cap). Furthermore, one sheet of PBT resin (product name: PBT Natural, manufactured by Alam Co.) with a diameter of approximately 1.0 cm, a weight of approximately 205 mg, and a thickness of approximately 2.0 mm was impregnated into each vial and quickly sealed. After heat treatment at 70°C for two weeks in a thermostatic bath, the weight of each resin was measured, and the weight change per unit volume was calculated using Formula 1. Evaluation can also be performed using the weight change relative to the initial weight. The volume of the PBT resin can also be calculated from the density and weight of the resin.

(Formula 1) Weight change per unit volume (mg/cm ³ ) =

(Weight of resin sheet after heat treatment - weight of resin sheet before heat treatment) / resin volume

The results of the tests conducted in this manner are shown in the lower columns of Tables 3 to 6.

As shown in the table, in each comparative example, an increase in the weight of the PBT resin-containing sheet was observed compared to before heat treatment. However, in the examples in which boric acid and borax were added, the weight change per unit volume of the PBT resin-containing sheet was suppressed compared to the comparative examples. This confirms that boric acid and borax suppress the weight change of the PBT resin-containing sheet caused by the ophthalmic aqueous composition containing component (A), and thus suppress the associated degradation of the PBT resin. While the mechanism of action is unclear, it is believed that the buffering capacity of component (B) may be responsible for the hydrogen ions in the ophthalmic aqueous composition having some effect on the chain molecular structure of the PBT resin.

<Evaluation of Weight Change 3>

(Examples 11 to 18)

Ophthalmic aqueous compositions were prepared to have the concentrations shown in Tables 7 to 13. The pH thereof was measured at room temperature using a HORIBA pH meter.

(Comparative Examples 13 to 22)

In the same manner as in Examples 11 to 18, ophthalmic aqueous compositions of Comparative Examples 13 to 22 shown in Tables 7 to 13 were prepared.

[Table 7]

[Table 8]

[Table 9]

[Table 10]

[Table 11]

[Table 12]

[Table 13]

(Test method)

2 mL of each test solution from the Examples and Comparative Examples was filled into a 10 mL clear glass vial (with a septum cap). Furthermore, one PBT resin sheet (product name: PBT Natural, manufactured by Alam Co., Ltd.) approximately 1.0 cm in diameter, weighing approximately 205 mg, and approximately 2.0 mm thick was impregnated into each vial and quickly sealed. After heat treatment at 75°C for one week in a thermostatic bath, the weight of each resin was measured, and the weight change per unit volume was calculated using Equation 1. Alternatively, the weight change relative to the initial weight can be used for evaluation. The volume of the PBT resin can also be calculated from the resin's density and weight.

(Formula 1) Weight change per unit volume (mg/cm ³ ) =

(Weight of resin sheet after heat treatment - weight of resin sheet before heat treatment) / resin volume

The results of the tests conducted in this manner are shown in the lower columns of Tables 7 to 13.

As shown in the table, in each Comparative Example, an increase in the weight of the PBT resin-containing sheet was observed compared to before heat treatment. However, in the Examples in which a buffer was added, the weight change per unit volume of the PBT resin-containing sheet was suppressed compared to the Comparative Examples. This confirms that the buffer suppresses the weight change of the PBT-containing resin caused by the ophthalmic aqueous composition containing component (A), and inhibits the associated degradation of the PBT-containing resin. While the mechanism of action is unclear, it is believed that the buffering capacity of component (B) may be responsible for the hydrogen ions in the ophthalmic aqueous composition having some effect on the chain molecular structure of the PBT-containing resin.

<Evaluation of advancing contact angle 1>

(Examples 19 to 87)

The ophthalmic aqueous compositions shown in Tables 14 to 32 were prepared by conventional methods to prepare test solutions. Using a contact angle meter DM-501 manufactured by Kyowa Interface Science Co., Ltd., the advancing contact angle, the contact angle at the interface between a solid and a liquid, was measured using the expansion/contraction method of the same measuring instrument. Specifically, a plate of PBT resin (product name: PBT Natural, manufactured by Alam Co.) in the shape of a regular square prism with a side of 50 mm and a thickness of approximately 2 mm was placed on the stage of the contact angle meter, and the test solution was placed in a dispenser. A 1 μL droplet of the test solution was dripped onto the PBT resin plate, forming a hemispherical shape. Next, the tip of the liquid ejection portion of the dispenser was quickly moved to drip onto the upper portion of the hemisphere. In this state, the test solution was continuously ejected at a rate of 6 μL/second, and the shape of the droplet was photographed 15 times every 0.1 seconds from the side. To ensure that the measurement conditions for the corresponding comparative example and the embodiment were consistent, the measurement was continued at the same room temperature using the same plate of PBT resin. Next, the analytical software FAMAS of the same measuring device was used to calculate the contact angles on the left and right sides of each image. Here, the contact angle refers to the angle formed by the tangent line drawn from the surface of the PBT resin plate, the test liquid, and the air at the contact point P in the test liquid and the tangent line drawn on the surface of the PBT resin plate, including the angle on the side of the test liquid. As the droplet expands by ejecting the test liquid, the contact angle changes, and then, an almost constant behavior is shown. Therefore, the average value of the contact angles on the left and right sides of each image is calculated. When the average values of the left and right contact angles are arranged in the order in which the images were taken and 5 consecutive ones are selected, the initial contact angle with the standard deviation of the average values of the 5 consecutive left and right contact angles initially being less than 2.5° is used as the advancing contact angle of the present invention. These operations are performed 3 times for each test liquid to calculate the advancing contact angle, and the average value of the 3 times is used as the advancing contact angle of the test liquid. In the case where the advancing contact angle does not change during the expansion of the droplet, the initial contact angle with the standard deviation of the average value of the 5 consecutive left and right contact angles initially being less than 2.5° is also used as the advancing contact angle of the present invention. The rate of increase of the advancing contact angle of the example relative to the advancing contact angle of the corresponding comparative example was calculated using the following formula (2).

<Formula (2)> Rising rate (%) = {(Advancing contact angle of each test liquid/Advancing contact angle of the comparative example) - 1} × 100

Comparative Examples are ophthalmic aqueous compositions in which component (B) is omitted from the Examples. For example, the comparative example corresponding to Example 19 in Table 14 is an ophthalmic aqueous composition containing 0.5 w/v% sodium chondroitin sulfate and adjusted to the same pH as Example 19, i.e., pH 5.1, using hydrochloric acid or sodium hydroxide.

In addition, unless otherwise noted in the table herein, the test was performed immediately after the test solution was prepared.

[Table 14]

[Table 15]

Unit: w/v% Example 27 Example 28 Example 29 (A) Cyanocobalamin 0.02 0.02 0.004 (B) Boric acid 0.5 0.5 - (B) Borax 0.02 0.02 - (B) Sodium citrate - - 0.1 (B)ε-aminocaproic acid - - 3 hydrochloric acid appropriate amount appropriate amount appropriate amount Sodium hydroxide appropriate amount appropriate amount appropriate amount pure water The remainder The remainder The remainder total 100 100 100 pH 6.9 5.2 7.0 Rise rate 12.4% 10.4% 10.1%

[Table 16]

[Table 17]

[Table 18]

In Examples 41 to 45 and the corresponding comparative examples, liquids heat-treated at 80° C. for one day were used for the tests.

[Table 19]

[Table 20]

[Table 21]

[Table 22]

[Table 23]

[Table 24]

[Table 25]

[Table 26]

In Example 68 and the corresponding comparative example, liquids heat-treated at 75° C. for 3 days were used for testing.

[Table 27]

[Table 28]

[Table 29]

[Table 30]

[Table 31]

[Table 32]

In Example 87 and the corresponding comparative example, a liquid heat-treated at 75° C. for 3 days was used for testing.

As shown in the tables, the Examples exhibited a higher rate of increase than the Comparative Examples that did not contain component (B). This confirmed that the ophthalmic aqueous composition containing component (B) in the ophthalmic aqueous composition containing component (A) was less likely to wet the PBT-containing resin during exercise. This indicates that beneficial effects such as improved liquid repellency with respect to the PBT-containing resin were achieved.

<Evaluation of Weight Change 4>

(Examples 88 to 122)

The components (A) and (B) and other components shown in Tables 33 to 53 were prepared at the concentrations shown in the tables, respectively. The pH was measured at room temperature using a HORIBA pH meter.

(Comparative Examples 23 to 63)

The ophthalmic aqueous compositions of the comparative examples shown in Tables 33 to 53 were prepared in the same manner as in the examples.

(Test method)

3 mL of each test solution from the Examples and Comparative Examples was filled into a 10 mL clear glass vial (with a septum cap). Furthermore, one PBT resin sheet (product name: PBT Natural, manufactured by Alam Co., Ltd.) approximately 1.0 cm in diameter, weighing approximately 205 mg, and approximately 2.0 mm thick was impregnated into each vial and quickly sealed. After heat treatment in a thermostatic bath at the temperature and for the number of days shown in the respective tables, the weight of each resin was measured, and the weight change per unit volume was calculated using Equation 1. Alternatively, the weight change relative to the initial weight can be used for evaluation. The volume of the PBT resin can also be calculated from the density and weight of the resin.

(Formula 1) Weight change per unit volume (mg/cm ³ ) =

(Weight of resin sheet after heat treatment - weight of resin sheet before heat treatment) / resin volume

The results of the experiments conducted in this manner are shown in the lower columns of the respective tables.

[Table 33]

The heat treatments of Comparative Examples 23 and 24 and Examples 88 and 89 were left to stand at 50°C for 7 days.

[Table 34]

The heat treatments of Comparative Examples 25 to 27 and Examples 90 and 91 were allowed to stand at 75°C for 3 days.

[Table 35]

The heat treatments of Comparative Examples 28, 29 and Example 92 were left to stand at 50°C for 12 days.

[Table 36]

The heat treatments of Comparative Examples 30, 31 and Example 93 were left to stand at 50°C for 17 days.

[Table 37]

The heat treatments of Comparative Examples 23, 32 and Example 94 were left to stand at 50°C for 7 days.

[Table 38]

The heat treatments of Comparative Examples 33, 34 and Example 95 were left to stand at 50°C for 12 days.

[Table 39]

The heat treatments of Comparative Examples 23, 35 to 37 and Examples 96 to 100 were left to stand at 50°C for 7 days.

[Table 40]

The heat treatments of Comparative Examples 23, 38 and Example 101 were left to stand at 50°C for 7 days.

[Table 41]

The heat treatments of Comparative Examples 39, 40 and Example 102 were left to stand at 50°C for 7 days.

[Table 42]

The heat treatments of Comparative Examples 41 to 43 and Examples 103 and 104 were allowed to stand at 50° C. for 12 days.

[Table 43]

The heat treatments of Comparative Examples 44 and 45 and Example 105 were left to stand at 75° C. for 3 days.

[Table 44]

The heat treatments of Comparative Examples 33, 46, and 47 and Examples 106 and 107 were left to stand at 50° C. for 12 days.

[Table 45]

The heat treatments of Comparative Examples 23, 48 to 50 and Examples 108 to 110 were left to stand at 50° C. for 7 days.

[Table 46]

The heat treatments of Comparative Examples 33, 51, and 52 and Examples 111 and 112 were left to stand at 50° C. for 12 days.

[Table 47]

The heat treatments of Comparative Examples 23, 53, 54 and Examples 113 and 114 were left to stand at 50°C for 7 days.

[Table 48]

The heat treatments of Comparative Examples 33, 55 and Example 115 were left to stand at 50°C for 12 days.

[Table 49]

The heat treatments of Comparative Examples 56, 57 and Example 116 were left to stand at 50°C for 7 days.

[Table 50]

The heat treatments of Comparative Examples 39, 58 and Example 117 were left to stand at 50°C for 7 days.

[Table 51]

The heat treatments of Comparative Examples 30, 59, and 60 and Examples 118 and 119 were performed by standing at 50° C. for 17 days.

[Table 52]

The heat treatments of Comparative Examples 39, 61 and Example 120 were left to stand at 50°C for 7 days.

[Table 53]

The heat treatments of Comparative Examples 23, 62, 63 and Examples 121 and 122 were left to stand at 50°C for 7 days.

<Preparation of ophthalmic aqueous composition and container storage example>

Prepare the ophthalmic aqueous compositions listed in Tables 54 to 57 (Tables 56 and 57 are each two pages long). Formulations 2, 3, 6, 9, 10, 15, and 18 to 21 were filled into a container body made of PET resin, a perforated plug made of PBT resin was installed in the opening of the body, and a cap made of PP resin was installed. Formulations 7 and 8 were filled into a container body made of PP resin, a perforated plug made of PBT resin was installed in the opening of the body, and a cap made of ABS resin was installed. Formulations 4 and 14 were filled into a container body made of ethylene-vinyl acetate copolymer resin, a perforated plug made of PBT resin was installed in the opening of the body, and a cap made of PE resin was installed. Formulations 1, 5, and 17 were filled into a container body made of PBT resin, a perforated plug made of PE resin was installed in the opening of the body, and a cap made of PS resin was installed. Formulations 11, 13, and 16 were filled into a container body made of PE resin. A PBT resin-based plug was installed in the opening of the body, and a PP resin-based cap was fitted. Formulation 12 was filled into a container containing an ophthalmic aqueous composition, the body and opening of which were made of the same PBT resin, and the container was capped with a PP resin-based cap. The values in the formulation examples are expressed in "w/v%."

[Table 54]

Preparation 1 Preparation 2 Preparation 3 Preparation 4 Preparation 5 Preparation 6 eye drops eye drops eye drops eye drops eye drops eye drops Tetrahydrozoline hydrochloride 0.05 0.05 0.03 Chlorpheniramine maleate 0.01 0.03 0.03 0.03 Dipotassium glycyrrhizate 0.25 Allantoin 0.2 zinc sulfate 0.05 Neostigmine methylsulfate 0.005 0.005 0.005 Pyridoxine hydrochloride 0.1 0.1 Tocopheryl acetate 0.015 Panthenol 0.1 Chondroitin sulfate sodium 0.05 0.05 0.5 0.5 0.05 Potassium L-aspartate 1 1 1 aminoethylsulfonic acid 0.1 1 1 1-Menthol 0.001 0.06 0.02 0.05 0.01 0.01 d-Camphor 0.01 0.03 0.01 0.001 d1-Camphor 0.02 d-borneol 0.001 0.01 0.02 0.005 Geraniol 0.001 Sodium hyaluronate 0.005 0.05 Hydroxypropyl methylcellulose 0.5 0.1 0.01 0.5 Hydroxyethyl cellulose 0.4 0.01 glucose 0.005 0.02 Polyhexanide hydrochloride 0.001 Benzalkonium chloride 0.02 0.01 0.005 Phenylethyl alcohol 0.05 Chlorobutanol 0.05 0.2 0.2 0.1 Sodium edetate 0.2 0.1 0.1 0.05 Sodium chloride 0.1 0.6 potassium chloride 0.2 0.1 ε-Aminocaproic acid 0.3 1 1 Boric acid 0.8 0.8 0.2 1 Borax 0.05 0.1 0.2 Sodium citrate .0.5 Sodium hydrogen phosphate 0.5 Polyoxyethylene hardened castor oil 0.4 0.1 0.01 Polysorbate 80 0.1 0.3 Propylene glycol 0.01 Dextran 0.2 Polyethylene glycol 40000 0.5 pH 6 5 6.5 5.7 7.8 6

[Table 55]

Preparation 7 Preparation 8 Preparation 9 Preparation 10 eye drops eye drops eye drops Eyewash Chlorpheniramine maleate 0.003 Dipotassium glycyrrhizate 0.025 zinc sulfate 0.01 Pyridoxine hydrochloride 0.01 Cyanocobalamin 0.001 Tocopheryl acetate 0.005 Chondroitin sulfate sodium 0.5 0.05 0.05 Potassium L-aspartate 0.5 0.1 aminoethylsulfonic acid 0.02 1-Menthol 0.005 0.02 0.05 d-Camphor 0.01 d1-Camphor 0.08 d-borneol 0.005 0.002 Geraniol 0.005 0.008 Sodium hyaluronate 0.1 0.01 0.001 Hydroxypropyl methylcellulose 0.005 0.1 0.01 Hydroxyethyl cellulose 0.005 glucose 0.001 0.1 Potassium sorbate 0.1 Polyhexanide hydrochloride 0.0001 Chlorhexidine gluconate 0.005 Chlorobutanol 0.3 Sodium edetate 0.01 0.001 0.002 0.02 Sodium chloride 1 0.5 0.01 potassium chloride 0.01 0.3 0.8 calcium chloride 0.005 Sodium bicarbonate 0.05 Boric acid 0.05 0.5 1.5 2 Borax 0.01 0.1 0.08 2-Amino-2-hydroxymethyl-1,3-propanediol 0.1 Polyoxyethylene hardened castor oil 0.5 0.01 0.3 0.1 Poloxamer 0.5 Polysorbate 80 0.01 0.6 pH 7 7 7 5.5

[Table 56]

[Table 57]

POE(200)POP(70) represents polyoxyethylene(200)polyoxypropylene(70)diol.

Claims (10)

1. An ophthalmic aqueous composition comprising a buffer and polyoxyethylene-cured castor oil, The buffer is one or more of boric acid or its salts. The concentration of the polyoxyethylene-cured castor oil is 0.1 w/v% to 2 w/v%. The concentration of one or more of the boronic acid or its salts is 0.21 w/v% to 1.8 w/v%. The ophthalmic aqueous composition is contained in a container formed of a resin containing polybutylene terephthalate, with part or all of the surface in contact with the ophthalmic aqueous composition being disposed of. 2. The ophthalmic aqueous composition of claim 1, further comprising one or more oils selected from sesame oil, castor oil, soybean oil, lanolin, liquid paraffin, and petrolatum; one or more vitamins selected from vitamin A and tocopherol acetate; and one or more cooling agents selected from eucalyptus oil and bergamot oil. 3. The ophthalmic aqueous composition of claim 2, wherein the ophthalmic aqueous composition contains an oil content of 0.00001 w/v% to 6 w/v. 4. The ophthalmic aqueous composition of claim 2, wherein the ophthalmic aqueous composition contains vitamins in a content of 0.00001 w/v% to 1.6 w/v. 5. The ophthalmic aqueous composition of claim 2, wherein the ophthalmic aqueous composition contains a cooling agent in an amount of 0.0001 w/v% to 1 w/v. 6. The ophthalmic aqueous composition of claim 1, further comprising polysorbate 80. 7. The ophthalmic aqueous composition of claim 1, further comprising an acidic polysaccharide. 8. The ophthalmic aqueous composition of claim 7, wherein the acidic polysaccharide is hyaluronic acid, chondroitin sulfate, dermatan sulfate, heparin, keratin sulfate, xanthan gum, gellan gum, alginic acid, or salts thereof. 9. The ophthalmic aqueous composition of claim 7, wherein the total content of the acidic polysaccharides is 0.0001 w/v% to 6 w/v. 10. A method for imparting an aqueous composition with the effect of inhibiting weight change of a resin container containing polybutylene terephthalate, wherein the effect of inhibiting weight change of the resin container containing polybutylene terephthalate is imparted to the aqueous composition by coexisting a buffer with polyoxyethylene-cured castor oil. The buffer is one or more of boric acid or its salts. The concentration of the polyoxyethylene-cured castor oil is 0.1 w/v% to 2 w/v%. The concentration of one or more of the boronic acid or its salts is 0.21 w/v% to 1.8 w/v.