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HK1233184A1 - Aqueous composition for ophthalmic use - Google Patents

Aqueous composition for ophthalmic use Download PDF

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Publication number
HK1233184A1
HK1233184A1 HK17106984.6A HK17106984A HK1233184A1 HK 1233184 A1 HK1233184 A1 HK 1233184A1 HK 17106984 A HK17106984 A HK 17106984A HK 1233184 A1 HK1233184 A1 HK 1233184A1
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HK
Hong Kong
Prior art keywords
oil
salts
aqueous composition
group
acid
Prior art date
Application number
HK17106984.6A
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Chinese (zh)
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HK1233184B (en
Inventor
水垂阳子
松村泰子
Original Assignee
日本乐敦制药株式会社
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Publication of HK1233184A1 publication Critical patent/HK1233184A1/en
Publication of HK1233184B publication Critical patent/HK1233184B/en

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Description

Ophthalmic aqueous composition
Technical Field
The present invention relates to an ophthalmic aqueous composition, a method for suppressing weight change of an ophthalmic polybutylene terephthalate-containing resin container, a method for suppressing deterioration of an ophthalmic polybutylene terephthalate-containing resin container, and a method for suppressing wetting of an ophthalmic polybutylene terephthalate-containing resin container.
Background
Polybutylene terephthalate-containing resins (hereinafter, also referred to as PBT-containing resins in the present specification) which are 1 type of thermoplastic polyester-based resins and are commonly used as thermoplastic resins are excellent in moldability and good in balance between physical properties and price, and have been used as container materials for automobiles, motors, electronic parts, semiconductor substrate containers, and the like.
Further, as a packaging bag for heating which accommodates a food composed of a liquid material and a solid material containing a large amount of water, oil and sugar therein, and which is not opened even when cooked by heating in a microwave oven or the like, a laminate in which a PBT film and a heat-adhesive resin layer are laminated has also been proposed (patent document 1).
Documents of the prior art
Patent document
Patent document 1: japanese patent laid-open No. 2006-143223
Disclosure of Invention
Thus, the PBT-containing resin has excellent properties, and when used as a container, has properties of absorbing moisture in the contents contained in the container.
Further, the PBT-containing resin is hydrolyzed by heat.
It is an object of the present invention to provide an ophthalmic aqueous composition which can solve such problems.
The present inventors have conducted extensive studies to solve the above problems, and as a result, have found that a PBT-containing resin container containing an ophthalmic aqueous composition can be stabilized and the container can be prevented from deteriorating by containing a specific component in the composition, thereby completing the present invention. Further, it has been found that a novel effect of improving wettability to a PBT-containing resin container (that is, suppressing wetting) and improving liquid repellency (liquid-repellency れ) can be obtained by using an ophthalmic aqueous composition containing a specific component.
Namely, the present invention provides the following:
[1]
an aqueous ophthalmic composition comprising (B) a buffer and (A) 1 or more selected from the group consisting of: polysaccharides; a monosaccharide; selected from vitamin B12Vitamin B, vitamin C21 or more vitamins selected from the group consisting of retinoids, and panthenol; 1 or more kinds of oil components selected from vegetable oil, animal oil, and mineral oil; is selected fromMore than 1 surfactant selected from polyoxyethylene castor oil, polyoxyethylene hardened castor oil, polyoxyethylene polyoxypropylene glycol, and polyoxyl stearate; 1 or more antiallergic components selected from tranilast, ketotifen, diphenhydramine, and their salts; 1 or more preservatives selected from chlorhexidine, sorbic acid, and salts thereof; 1 or more thickening components selected from the group consisting of carboxymethyl cellulose, methyl cellulose, vinyl polymer compounds, and salts thereof; a polyol; 1 or more antiinflammatory components selected from berberine, azulene sulfonic acid, allantoin, zinc sulfate, and their salts; selected from the group consisting of sulfamethoxazole1 or more antibacterial agents selected from oxazole and salts thereof; 1 or more of 1 or more cooling agents selected from eucalyptus oil and bergamot oil,
the ophthalmic aqueous composition is contained in a container (C) in which a part or the whole of the surface in contact with the ophthalmic aqueous composition is molded with a resin containing polybutylene terephthalate.
[2]
As in item [1]The ophthalmic aqueous composition according to (1), wherein in the component (A), the polysaccharide is at least one selected from alginic acid, gellan gum, xanthan gum, hyaluronic acid, chondroitin sulfate, and salts thereof; the monosaccharide is glucose; vitamins are selected from cyanocobalamin, retinol, panthenol, flavin adenine dinucleotide, and 1 or more of their salts; the oil component is selected from more than 1 of oleum Sesami, oleum ricini, lanolin, vaseline, and liquid paraffin; the surfactant is more than 1 selected from polyoxyethylene castor oil, polyoxyethylene hardened castor oil, polyoxyethylene polyoxypropylene glycol and polyoxyl stearate; the antiallergic component is more than 1 selected from tranilast, ketotifen fumarate, and diphenhydramine hydrochloride; the antiseptic is more than 1 selected from chlorhexidine gluconate and potassium sorbate; the viscosity-increasing component is selected from carboxymethyl cellulose, methyl cellulose, polyvinylpyrrolidone, and carboxymethyl cellulose1 or more of vinyl-based polymers and salts thereof; the polyhydric alcohol is more than 1 selected from propylene glycol, glycerol and mannitol; the anti-inflammatory component is more than 1 selected from berberine chloride, sodium azulene sulfonate, allantoin and zinc sulfate; the antibacterial agent is sulfamethoxazoleSodium oxazole; the cooling agent is more than 1 selected from oleum Eucalypti and bergamot oil.
[3]
The ophthalmic aqueous composition as described in the item [1] or [2], which further comprises sodium edetate.
[4]
A method for imparting an effect of suppressing a change in weight of a polybutylene terephthalate-containing resin container to an aqueous composition, wherein in the aqueous composition, (B) a buffer and (A) 1 or more selected from the group consisting of: polysaccharides; a monosaccharide; selected from vitamin B12Vitamin B, vitamin C21 or more vitamins selected from the group consisting of retinoids, and panthenol; 1 or more kinds of oil components selected from vegetable oil, animal oil, and mineral oil; 1 or more surfactants selected from polyoxyethylene castor oil, polyoxyethylene hardened castor oil, polyoxyethylene polyoxypropylene glycol, and polyoxyl stearate; 1 or more antiallergic components selected from tranilast, ketotifen, diphenhydramine, and their salts; 1 or more preservatives selected from chlorhexidine, sorbic acid, and salts thereof; 1 or more thickening components selected from the group consisting of carboxymethyl cellulose, methyl cellulose, vinyl polymer compounds, and salts thereof; a polyol; 1 or more antiinflammatory components selected from berberine, azulene sulfonic acid, allantoin, zinc sulfate, and their salts; selected from the group consisting of sulfamethoxazole1 or more antibacterial agents selected from oxazole and salts thereof; more than 1 kind selected from oleum Eucalypti and bergamot oilThereby imparting an effect of suppressing a weight change of the polybutylene terephthalate-containing resin container to the aqueous composition.
[5]
A method for imparting an effect of suppressing wetting of a polybutylene terephthalate-containing resin container to an aqueous composition, wherein in the aqueous composition, (B) a buffer and (A) 1 or more selected from the group consisting of: polysaccharides; a monosaccharide; selected from vitamin B12Vitamin B, vitamin C21 or more vitamins selected from the group consisting of retinoids, and panthenol; 1 or more kinds of oil components selected from vegetable oil, animal oil, and mineral oil; 1 or more surfactants selected from polyoxyethylene castor oil, polyoxyethylene hardened castor oil, polyoxyethylene polyoxypropylene glycol, and polyoxyl stearate; 1 or more antiallergic components selected from tranilast, ketotifen, diphenhydramine, and their salts; 1 or more preservatives selected from chlorhexidine, sorbic acid, and salts thereof; 1 or more thickening components selected from the group consisting of carboxymethyl cellulose, methyl cellulose, vinyl polymer compounds, and salts thereof; a polyol; 1 or more antiinflammatory components selected from berberine, azulene sulfonic acid, allantoin, zinc sulfate, and their salts; selected from the group consisting of sulfamethoxazole1 or more antibacterial agents selected from oxazole and salts thereof; 1 or more of 1 or more cooling agents selected from eucalyptus oil and bergamot oil, thereby imparting an effect of suppressing wetting of the polybutylene terephthalate-containing resin container to the aqueous composition.
[6]
A liquid repellency enhancer for an ophthalmic polybutylene terephthalate-containing resin container, comprising (B) a buffer and (A) 1 or more selected from the group consisting of: polysaccharides; a monosaccharide; selected from vitamin B12Vitamin B, vitamin C21 or more of vitamin A, and panthenolThe vitamins of (1); 1 or more kinds of oil components selected from vegetable oil, animal oil, and mineral oil; 1 or more surfactants selected from polyoxyethylene castor oil, polyoxyethylene hardened castor oil, polyoxyethylene polyoxypropylene glycol, and polyoxyl stearate; 1 or more antiallergic components selected from tranilast, ketotifen, diphenhydramine, and their salts; 1 or more preservatives selected from chlorhexidine, sorbic acid, and salts thereof; 1 or more thickening components selected from the group consisting of carboxymethyl cellulose, methyl cellulose, vinyl polymer compounds, and salts thereof; a polyol; 1 or more antiinflammatory components selected from berberine, azulene sulfonic acid, allantoin, zinc sulfate, and their salts; selected from the group consisting of sulfamethoxazole1 or more antibacterial agents selected from oxazole and salts thereof; more than 1 kind of cooling agent selected from oleum Eucalypti and bergamot oil.
The ophthalmic aqueous composition, the method for suppressing weight change, the method for suppressing deterioration, the method for suppressing wetting, the agent for improving liquid repellency, the method for improving liquid repellency, and the method for producing the same of the present invention can use the components and concentrations described below.
The ophthalmic aqueous composition of the present invention can stabilize a container and suppress deterioration of the container when contained in a PBT-containing resin container. Further, it is desirable to suppress wetting and improve lyophobicity and to reduce the liquid residue in the container.
Drawings
FIG. 1 is a graph showing the change in weight of a PBT-containing resin sheet before and after a PBT-containing resin sheet is immersed in an ophthalmic aqueous composition and heat-treated.
Detailed Description
In the present invention, the unit of "w/v%" of the content is synonymous with "g/100 mL". In the present invention, "blending amount" is synonymous with "content".
The inventors of the present invention have found that when an ophthalmic aqueous composition is contained in a PBT-containing resin container, the PBT-containing resin undergoes a weight change, which causes problems such as a decrease in the strength of the container, a crack, a deformation, and a decrease in sealing properties, that is, when a container made of a PBT-containing resin is used while storing a drug such as an ophthalmic aqueous composition for a certain period of time, the problem of a change in the properties of the PBT-containing resin container becomes serious. The ophthalmic aqueous composition of the present invention can solve such a problem.
The ophthalmic aqueous composition of the present invention contains (B) a buffer and (A) 1 or more selected from the group consisting of: polysaccharides; a monosaccharide; selected from vitamin B12Vitamin B, vitamin C21 or more vitamins selected from the group consisting of retinoids, and panthenol; 1 or more kinds of oil components selected from vegetable oil, animal oil, and mineral oil; 1 or more surfactants selected from polyoxyethylene castor oil, polyoxyethylene hardened castor oil, polyoxyethylene polyoxypropylene glycol, and polyoxyl stearate; 1 or more antiallergic components selected from tranilast, ketotifen, diphenhydramine, and their salts; 1 or more preservatives selected from chlorhexidine, sorbic acid, and salts thereof; 1 or more thickening components selected from the group consisting of carboxymethyl cellulose, methyl cellulose, vinyl polymer compounds, and salts thereof; a polyol; 1 or more antiinflammatory components selected from berberine, azulene sulfonic acid, allantoin, zinc sulfate, and their salts; selected from the group consisting of sulfamethoxazole1 or more antibacterial agents selected from oxazole and salts thereof; more than 1 kind of cooling agent selected from oleum Eucalypti and bergamot oil. The ophthalmic aqueous composition of the present invention is contained in a PBT-containing resin container.
In the present invention, the aqueous composition means a composition containing water. The aqueous composition preferably contains water in an amount of 50 w/v% or more, more preferably 70 w/v% or more, further 80 w/v% or more, further preferably 85 w/v% or more, and particularly preferably 90 w/v% or more, based on the total amount of the aqueous composition. In the present invention, the ophthalmic aqueous composition refers to all ophthalmic aqueous compositions such as eye drops (synonymous with eye drops or eye drops), eye washes (synonymous with eye washes or eye washes), contact lens wetting solutions, contact lens cleaning solutions, contact lens preserving solutions, and contact lens disinfecting solutions.
In the ophthalmic aqueous composition of the present invention, as the component (a), 1 or more selected from the following substances can be used: polysaccharides; a monosaccharide; selected from vitamin B12Vitamin B, vitamin C21 or more vitamins selected from the group consisting of retinoids, and panthenol; 1 or more kinds of oil components selected from vegetable oil, animal oil, and mineral oil; 1 or more surfactants selected from polyoxyethylene castor oil, polyoxyethylene hardened castor oil, polyoxyethylene polyoxypropylene glycol, and polyoxyl stearate; 1 or more antiallergic components selected from tranilast, ketotifen, diphenhydramine, and their salts; 1 or more preservatives selected from chlorhexidine, sorbic acid, and salts thereof; 1 or more thickening components selected from the group consisting of carboxymethyl cellulose, methyl cellulose, vinyl polymer compounds, and salts thereof; a polyol; 1 or more antiinflammatory components selected from berberine, azulene sulfonic acid, allantoin, zinc sulfate, and their salts; selected from the group consisting of sulfamethoxazole1 or more antibacterial agents selected from oxazole and salts thereof; more than 1 kind of cooling agent selected from oleum Eucalypti and bergamot oil.
In the present invention, these (a) components may be used alone or in combination of 2 or more. (A) The components can be obtained from natural sources or chemically synthesized components. (A) Ingredients any commercially available ingredient may also be used.
In the present invention, the polysaccharide of component (a) is preferably an acidic polysaccharide. The acidic polysaccharide refers to a polysaccharide having a repeating structure of 2 or more monosaccharides and containing an acidic group. Here, the acidic group is not limited, but is particularly a carboxyl group or a sulfuric acid group. The constituent components of the repeating structure are not limited, but examples thereof include uronic acids such as glucuronic acid, iduronic acid, mannuronic acid, guluronic acid, etc., aminosugars such as galactosamine, glucosamine, etc., galactose, mannose, glucose, rhamnose, etc.
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.
The acidic polysaccharide as the component (a) may be a naturally-obtained component or a chemically-synthesized component, and the source thereof is not particularly limited. Commercially available acidic polysaccharides may also be used. The acidic polysaccharides may be in the form of alkali metal salts such as sodium and potassium, alkaline earth metal salts such as calcium and magnesium, metal salts such as iron and manganese, and other physiologically or pharmaceutically acceptable salts. In addition, acetylated reactants may also be used. These acidic polysaccharides may be used alone or in combination of two or more. The acidic polysaccharide as the component (a) is preferably chondroitin sulfate, hyaluronic acid, xanthan gum, gellan gum, alginic acid, and salts thereof, and particularly preferably sodium chondroitin sulfate, sodium hyaluronate, alginic acid, and gellan gum.
(A) The molecular weight of the acidic polysaccharide as the component (a) varies depending on the number and type of repeating units, and is not limited, and may be several hundred to several million in weight average molecular weight. The molecular weight of the acidic polysaccharide as the component (a) is preferably 0.01 to 500 ten thousand, more preferably 0.05 to 300 ten thousand, in terms of the weight average molecular weight, from the viewpoint of suppressing deterioration of the PBT-containing resin container and the like and obtaining the effects of the present invention more significantly. More specifically, for example, the weight average molecular weight of chondroitin sulfate or a salt thereof is preferably 0.1 to 300 ten thousand, more preferably 0.5 to 150 ten thousand, and further preferably 1 to 50 ten thousand. More specifically, for example, the weight average molecular weight of hyaluronic acid or a salt thereof is preferably 10 to 500 ten thousand, more preferably 50 to 400 ten thousand, and further preferably 60 to 250 ten thousand.
In the present invention, the monosaccharide as component (a) includes aldoses such as Glucose (Glucose), ribose, glyceraldehyde, erythrose, threose, lyxose, xylose, arabinose, allose, talose, gulose, altrose, mannose, galactose, and idose, and ketoses such as dihydroxyacetone, erythrulose, xylulose, ribulose, psicose, fructose, sorbose, and tagatose. Among them, glucose, galactose, mannose, fructose, and sorbose are preferable, and glucose is particularly preferable. These may be used alone or in combination of 2 or more. Commercially available monosaccharides can also be used as such monosaccharides.
In the present invention, the vitamin of component (A) may be a fat-soluble vitamin or a water-soluble vitamin, and the fat-soluble vitamin may be at least 1 of vitamin A compounds selected from the group consisting of retinol, retinol acetate, retinol palmitate, retinal, retinoic acid, methyl retinoic acid, ethyl retinoic acid, retinol ester, vitamin A fatty acid ester, d-tocopherol retinoic acid ester, α -tocopherol retinoic acid ester, β -tocopherol retinoic acid ester, carotene, dehydroretinal, lycopene, and salts thereof, and the water-soluble vitamin may be, for example, a vitamin B2 compound selected from the group consisting of riboflavin, flavin mononucleotide, flavin adenine dinucleotide, riboflavin butyrate, riboflavin tetrabutyrate, riboflavin 5' -sodium phosphate, riboflavin tetranicotinate, and salts thereof, cyanocobalamin, hydroxycobalamin, methylcobalamin, deoxyadenosylcobalamin, and salts thereof, and the like12Class; and 1 or more of the present polyols (panthenol).
(A) The vitamins of component (a) are preferably at least 1 selected from the group consisting of cyanocobalamin, retinol, panthenol, flavin adenine dinucleotide and salts thereof, and particularly preferably at least 1 selected from the group consisting of cyanocobalamin, retinol palmitate, retinol acetate, panthenol and flavin adenine dinucleotide sodium. Examples of the vitamin a include 0.550 μ g of retinol palmitate manufactured by DSM corporation, which is vitamin a1i.u. The i.u. is an international unit obtained by sixteenth modification of the method described in japanese pharmacopoeia, for example, the method for quantitative determination of vitamin a.
These vitamins may be used alone or in combination of two or more. Any commercially available vitamin may be used as the vitamin.
In the present invention, the oil component of component (a) may be 1 or more oil components selected from vegetable oils, animal oils, and mineral oils. When an oil component is used as the component (a), a vegetable oil and/or a mineral oil is more preferable from the viewpoint of more remarkably obtaining the effect of the present invention.
Here, the vegetable oil is not particularly limited as long as it is an oil using a plant as a raw material. Preferably a vegetable oil containing triglycerides. (A) The vegetable oil as the component (b) is not limited, and specific examples thereof include sesame oil, castor oil, soybean oil, peanut oil, almond oil, wheat germ oil, camellia oil, corn oil, rapeseed oil, sunflower seed oil, cottonseed oil, olive oil, and derivatives thereof. The vegetable oil as the component (a) is preferably sesame oil, castor oil, soybean oil, or a derivative thereof, and particularly preferably sesame oil or castor oil. These vegetable oils may be used alone or in combination of two or more. Commercially available vegetable oils can also be used.
(A) The animal oil as the component (b) is not limited, and specific examples thereof include squalane, lanolin, orange roughy oil, horse oil, whale oil, liver oil, mink oil, margarine, beef tallow, milk fat, lard, and the like. The animal oil as the component (a) is preferably squalane, lanolin, egg yolk oil, or a derivative thereof, and particularly preferably squalane or purified lanolin. Here, the animal oil is not particularly limited as long as it is an oil using an animal as a raw material. These animal oils may be used alone or in combination of two or more. Any commercially available animal oil can be used.
(A) The mineral oil as the component (b) is a liquid or paste-like (グリース -like) chemical substance obtained by refining a hydrocarbon oil derived from natural petroleum. (A) The mineral oil as the component (b) is not limited, and specific examples thereof include paraffin oil, liquid paraffin, and vaseline, and liquid paraffin, light liquid paraffin, and white vaseline are particularly preferable. These mineral oils may be used alone or in combination of two or more. Any commercially available mineral oil can be used. For example, Haikoru M-202 manufactured by Kaneda corporation, etc. can be mentioned as the liquid paraffin.
In the present invention, the surfactant of component (a) may be 1 or more selected from polyoxyethylene castor oil, polyoxyethylene hardened castor oil, polyoxyethylene polyoxypropylene glycol, and polyoxyl stearate.
Specific examples of such surfactants include polyoxyethylene polyoxypropylene glycols such as poloxamer 407, polyoxyethylene (200) polyoxypropylene (70) glycol, poloxamer 188, polyoxyethylene (120) polyoxypropylene (40) glycol, polyoxyethylene (54) polyoxypropylene (39) glycol, polyoxyethylene (20) polyoxypropylene (20) glycol, TETRONIC, and the like; polyoxyethylene hardened castor oil such as 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 60, and polyoxyethylene hardened castor oil 100; polyoxyethylene castor oils such as 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, and polyoxyethylene castor oil 60; polyoxyl stearate such as polyoxyl stearate 40 and polyoxyl stearate 140.
(A) Among the surfactants of the components, poloxamer 407, polyoxyethylene (200) polyoxypropylene (70) glycol, polyoxyethylene hardened castor oil 40, polyoxyethylene hardened castor oil 60, polyoxyethylene castor oil 3, polyoxyethylene castor oil 10, polyoxyethylene castor oil 35, polyoxyl stearate 40, polyoxyl stearate 140 are preferable, and poloxamer 407, polyoxyethylene hardened castor oil 60, polyoxyethylene castor oil 10, polyoxyethylene castor oil 35, polyoxyl stearate 40 are more preferable.
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 moles, preferably 2 to 60 moles, more preferably 3 to 50 moles, and particularly preferably 3 to 40 moles. The average number of moles of ethylene oxide added to the polyoxyethylene polyoxypropylene glycol used as component (A) is not particularly limited, and may be, for example, 10 to 350 moles, preferably 30 to 300 moles, more preferably 50 to 300 moles, and particularly preferably 100 to 250 moles. The average number of moles of ethylene oxide added to the polyoxyethylene hardened castor oil used as the component (a) is not particularly limited, and may be 3 to 120 moles, preferably 20 to 100 moles, and more preferably 30 to 80 moles. The average number of moles of ethylene oxide added to the polyoxy stearate used as the component (A) is not particularly limited, and may be 3 to 200 moles, preferably 20 to 180 moles, and more preferably 30 to 160 moles.
In the present invention, the component (a) may be 1 or more antiallergic components selected from tranilast, ketotifen, diphenhydramine, and salts thereof. Among the antiallergic ingredients, tranilast, ketotifen fumarate, and diphenhydramine hydrochloride are preferable.
In the present invention, the component (a) may be 1 or more preservatives selected from chlorhexidine, sorbic acid, and salts thereof. Preferred preservatives include chlorhexidine gluconate, sorbic acid and potassium sorbate.
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 may be, for example, carboxymethyl cellulose, methyl cellulose, and salts thereof. The vinyl polymer compound is not particularly limited, and examples thereof include polyvinyl pyrrolidone, polyvinyl alcohol (completely or partially saponified product), carboxyvinyl polymer, and salts thereof. (A) The thickening component of the component (a) is preferably carboxymethylcellulose, methylcellulose, a vinyl polymer compound, or a salt thereof, more preferably carboxymethylcellulose, sodium carboxymethylcellulose, methylcellulose, polyvinylpyrrolidone, and a carboxyvinyl polymer, further preferably carboxymethylcellulose, sodium carboxymethylcellulose, methylcellulose, polyvinylpyrrolidone K17, polyvinylpyrrolidone K25, polyvinylpyrrolidone K30, polyvinylpyrrolidone K90, and a carboxyvinyl polymer, and particularly preferably carboxymethylcellulose, sodium carboxymethylcellulose, methylcellulose, polyvinylpyrrolidone K25, polyvinylpyrrolidone K30, polyvinylpyrrolidone K90, and a carboxyvinyl polymer.
In the present invention, the component (A) may be a polyol. The polyhydric alcohol is not limited, but is preferably 1 or more polyhydric alcohols selected from propylene glycol, glycerin, and mannitol.
In the present invention, the component (a) may be at least 1 anti-inflammatory component selected from berberine, azulene sulfonic acid, allantoin, zinc sulfate, or salts thereof. Among the anti-inflammatory components, berberine sulfate, berberine chloride, sodium azulene sulfonate, allantoin and zinc sulfate are preferred.
In the present invention, the component (A) may be selected from the group consisting of sulfamethoxazoleAzole or a salt thereof. Here, sulfamethoxazoleThe salt of oxazole is preferably sulfamethoxazoleSodium oxazole.
In the present invention, the component (a) may be 1 or more kinds of cooling agents selected from eucalyptus oil and bergamot oil.
These (A) components can be used alone in 1 kind, also can be arbitrarily combined and used 2 or more. Combinations of 2 or more are particularly preferred. In the case of 2 or more species, for example, 2 or more species of different substances of the same classification may be used, or 2 or more species of different substances of different classifications may be used. For example, 2 or more kinds of polysaccharides may be contained, or 1 or more kinds of polysaccharides and 1 or more kinds of vitamins may be selected and combined. The same applies to the component (A) such as monosaccharide, oil component, surfactant, antiallergic component, antiseptic, thickening component, polyol, antiinflammatory component, antibacterial agent, and refreshing agent.
In the ophthalmic aqueous composition of the present invention, the total content of the component (a) to the total amount of the ophthalmic aqueous composition can be appropriately set depending on the type of the component (a) and the types and contents of other components to be blended, from the viewpoint of more remarkably obtaining the effect of the present invention. The total content of the component (A) is preferably 0.0001 w/v% or more, more preferably 0.001 w/v% or more, still more preferably 0.005 w/v% or more, and further preferably 0.01 w/v% or more, based on the total amount of the ophthalmic aqueous composition. The total content of the component (A) is preferably 20 w/v% or less, more preferably 10 w/v% or less, still more preferably 5 w/v% or less, more preferably 3 w/v% or less, and most preferably 1 w/v% or less, based on the total amount of the ophthalmic aqueous composition.
The total content of the polysaccharide of the present invention relative to the total amount of the ophthalmic aqueous composition may be appropriately set depending on the type of the component (A) and the type and content of other components to be added. From the viewpoint of more remarkably obtaining the effect of the present invention, the total content of the polysaccharides is preferably 0.0001 w/v% to 6 w/v%, more preferably 0.0005 w/v% to 4 w/v%, and particularly preferably 0.001 w/v% to 2 w/v% based on the total amount of the ophthalmic aqueous composition.
Although not limited thereto, in a preferred embodiment, for example, when chondroitin sulfate or a salt thereof is contained as the component (A), the content of chondroitin sulfate or a salt thereof is preferably 0.0001 w/v% to 5 w/v% of the total amount of the ophthalmic aqueous composition, and more preferably 0.005 w/v% to 3 w/v%. Similarly, in another preferred embodiment, when hyaluronic acid or a salt thereof is contained as the component (A), the content of hyaluronic acid or a salt thereof 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% of the total amount of the ophthalmic aqueous composition.
The total content of the monosaccharide(s) in the present invention relative to the total amount of the ophthalmic aqueous composition may be appropriately set depending on the type of the component (a) and the type and content of other components to be blended. From the viewpoint of more remarkably obtaining the effect of the present invention, the total content of the monosaccharide is preferably 0.0001 w/v% to 3 w/v%, more preferably 0.005 w/v% to 1.5 w/v%, and particularly preferably 0.001 w/v% to 0.5 w/v% with respect to the total amount of the ophthalmic aqueous composition.
In another preferred embodiment, when glucose is contained as the component (A), the content of glucose alone 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% of the total amount of the ophthalmic aqueous composition.
The total content of vitamins of the present invention with respect to the total amount of the ophthalmic aqueous composition can be appropriately set depending on the type of the component (a) and the type and content of other components to be blended. From the viewpoint of more significantly obtaining the effect of the present invention, the total content of vitamins is preferably 0.00001 w/v% to 1.6 w/v%, more preferably 0.0005 w/v% to 0.8 w/v%, and particularly preferably 0.0005 w/v% to 0.4 w/v% based on the total amount of the ophthalmic aqueous composition.
Although not limited thereto, in a preferred embodiment, when the retinol palmitate is contained as the component (A), the retinol palmitate is contained in an amount of preferably 10 to 500000 units/100 mL, more preferably 100 to 300000 units/100 mL, and further preferably 500 to 200000 units/100 mL, based on the total amount of the ophthalmic aqueous composition. Also, depending on the unit of retinol palmitate to be blended, it is preferably contained in an amount of 0.005 to 0.5W/V%, more preferably 0.001 to 0.4W/V%, and still more preferably 0.01 to 0.3W/V%. Similarly, in another preferred embodiment, for example, cyanocobalamin is contained as the component (A) alone, preferably in an amount of 0.00001 to 1 w/v%, more preferably in an amount of 0.00005 to 0.5 w/v%, and particularly preferably in an amount of 0.0001 to 0.02 w/v% of the total amount of the ophthalmic aqueous composition.
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 the component (A), and the type and content of other components to be blended. From the viewpoint of more remarkably obtaining the effect of the present invention, the total content of the oil component is preferably 0.00001 w/v% to 6 w/v%, more preferably 0.0005 w/v% to 3 w/v%, and particularly preferably 0.0001 w/v% to 1 w/v% with respect to the total amount of the ophthalmic aqueous composition.
Although not limited thereto, in a preferred embodiment, for example, when sesame oil is contained as the component (A), the content of the sesame oil alone is preferably 0.00001 to 5 w/v%, more preferably 0.0001 to 1 w/v% of the total amount of the ophthalmic aqueous composition. Similarly, in another preferred embodiment, for example, when castor oil is contained as the component (A), the content of castor oil alone is preferably 0.00001 to 5 w/v%, and more preferably 0.0001 to 1 w/v% of the total amount of the ophthalmic aqueous composition. Similarly, in another preferred embodiment, when liquid paraffin is contained as the component (A), the content of the liquid paraffin alone is preferably 0.00001 to 2 w/v%, more preferably 0.0001 to 1 w/v% of the total amount of the ophthalmic aqueous composition. Similarly, in another preferred embodiment, when vaseline is contained as the component (A), the content of vaseline alone is preferably 0.00001 to 5 w/v%, more preferably 0.00005 to 1 w/v% of the total amount of the ophthalmic aqueous composition.
The total content of the surfactant of the present invention relative to the total amount of the ophthalmic aqueous composition can be appropriately set depending on the kind of the component (a), and the kind and content of other components to be blended. From the viewpoint of more remarkably obtaining the effect of the present invention, the total content of the surfactant is preferably 0.00001 w/v% to 10 w/v%, more preferably 0.0001 w/v% to 8 w/v%, and particularly preferably 0.001 w/v% to 5 w/v% based on the total amount of the ophthalmic aqueous composition.
Although not limited thereto, in a preferred embodiment, for example, when polyoxyethylene polyoxypropylene glycol is contained as the component (A), the content of polyoxyethylene polyoxypropylene glycol alone is preferably 0.00001 w/v% to 10 w/v%, more preferably 0.0001 w/v% to 8 w/v%, and particularly preferably 0.001 w/v% to 5 w/v% of the total amount of the ophthalmic aqueous composition. Similarly, in another preferred embodiment, when the polyoxyethylene castor oil is contained as the component (A), the polyoxyethylene castor oil is contained in an amount of preferably 0.00001 to 10 w/v%, more preferably 0.0001 to 5 w/v%, and particularly preferably 0.001 to 3 w/v% of the total amount of the ophthalmic aqueous composition.
The total content of the antiallergic component(s) of the present invention relative to the total amount of the ophthalmic aqueous composition is preferably 0.00001 to 5 w/v%, more preferably 0.0005 to 1 w/v%, and particularly preferably 0.0005 to 0.5 w/v%, relative to the total amount of the ophthalmic aqueous composition, from the viewpoint of more significantly obtaining the effect 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 to 2 w/v%, more preferably 0.00005 to 1 w/v%, and particularly preferably 0.0001 to 0.5 w/v%, relative to the total amount of the ophthalmic aqueous composition, from the viewpoint of more significantly obtaining the effect 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 obtaining the effect of the present invention.
The total content of the polyhydric alcohol relative to the total amount of the ophthalmic aqueous composition of the present invention is preferably 0.00005 to 10 w/v%, more preferably 0.0001 to 8 w/v%, and particularly preferably 0.005 to 5 w/v%, relative to the total amount of the ophthalmic aqueous composition, from the viewpoint of more significantly obtaining the effect 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 to 3 w/v%, more preferably 0.00005 to 1.5 w/v%, and particularly preferably 0.0001 to 0.6 w/v%, relative to the total amount of the ophthalmic aqueous composition, from the viewpoint of more significantly obtaining the effect 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 obtaining the effect 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 obtaining the effect of the present invention.
In the present invention, the buffer of component (B) may be an inorganic buffer or an organic buffer.
The inorganic buffer of the 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 thereof include alkali metal salts, alkaline earth metal salts, and salts with organic bases of boric acid. More specifically, there may be mentioned sodium, potassium, calcium, magnesium, ammonium, or a salt with diethanolamine, ethylenediamine or the like of boric acid. Preferable examples of the borate include, but are not limited to, borax, sodium borate, ammonium borate, potassium tetraborate, and the like. Among them, borax is particularly preferably used.
The organic buffer of component (B) of the present invention is preferably aminocaproic acid, phosphoric acid, citric acid, carbonic acid, or 2-amino-2-hydroxymethyl-1, 3-propanediol (tris, tromethamine, trihydroxymethylaminomethane), or a salt thereof. The salts thereof are not particularly limited as long as they are physiologically or pharmaceutically acceptable. Examples thereof include alkali metal salts, alkaline earth metal salts, and salts with organic bases of aminocaproic acid, phosphoric acid, citric acid, carbonic acid, or 2-amino-2-hydroxymethyl-1, 3-propanediol. Preferably, sodium, potassium, calcium, magnesium, ammonium, or a salt with diethanolamine, ethylenediamine, or the like is mentioned.
In the present invention, these (B) components may be used alone or in combination of 2 or more. (B) The components can be obtained from natural sources or chemically synthesized components. (B) Any commercially available component may be used.
In the ophthalmic aqueous composition of the present invention, the total content of the component (B) is preferably 0.001 w/v% or more, more preferably 0.01 w/v% or more, and still more preferably 0.1 w/v% or more, based on the total amount of the ophthalmic aqueous composition, from the viewpoint of more remarkably obtaining the effects of the present invention. The total content of component (B) is preferably 20 w/v% or less, more preferably 15 w/v% or less, still more preferably 10 w/v% or less, yet more preferably 5 w/v% or less, and most preferably 3 w/v% or less, based on the total amount of the ophthalmic aqueous composition.
Although not limited thereto, in a preferred embodiment, for example, when the component (B) is aminocaproic acid or 2-amino-2-hydroxymethyl-1, 3-propanediol, the content of aminocaproic acid or 2-amino-2-hydroxymethyl-1, 3-propanediol alone is preferably 0.001 w/v% to 6 w/v%, more preferably 0.01 w/v% to 8 w/v%, particularly preferably 0.05 w/v% to 5 w/v% of the total amount of the ophthalmic aqueous composition. Similarly, in another preferred embodiment, when boric acid, phosphoric acid, citric acid, carbonic acid, or a salt thereof is contained as the component (B), the content of boric acid, phosphoric acid, citric acid, carbonic acid, or a salt thereof alone is preferably 0.001 w/v% to 5 w/v%, more preferably 0.005 w/v% to 4 w/v%, and particularly preferably 0.01 w/v% to 3 w/v% of the total amount of the ophthalmic aqueous composition.
In the ophthalmic aqueous composition of the present invention, from the viewpoint of more remarkably obtaining the effect of the present invention, the total content of the component (B) is preferably 0.00001 to 10000 parts by weight, more preferably 0.0001 to 5000 parts by weight, even more preferably 0.0005 to 3000 parts by weight, particularly preferably 0.001 to 2000 parts by weight, and most preferably 0.01 to 1000 parts by weight, based on 1 part by weight of the total content of the component (a) relative to the content of the component (B) of the component (a).
In the ophthalmic aqueous composition of the present invention, the combination of the component (a) and the component (B) is not particularly limited, and may be appropriately set according to the kinds of the component (a) and the component (B). The combinations are exemplified in table 1 below for up to 2 pages.
[ Table 1]
In the present invention, the PBT-containing resin container means an ophthalmic container, and a part or the whole of the container means a container molded with a resin containing polybutylene terephthalate. Here, the "part of the container" means at least a part of a part which comes into contact with the ophthalmic aqueous composition contained inside. The portion in contact with the ophthalmic aqueous composition may be the innermost layer of a structure comprising a plurality of layers including an inner plug, an opening inner plug, and a container inner surface. For example, in a container having an open-celled internal plug (nozzle), only the internal plug portion may be formed of a PBT-containing resin. Alternatively, the receiving portion and the like other than the inside plug may be formed of a PBT-containing resin. Alternatively, the entire container may be molded from a PBT-containing resin. At least a part of the surface to be in contact with the ophthalmic aqueous composition may be composed of a PBT-containing resin, and most preferably, the entire surface to be in contact with is composed of a PBT-containing resin. When a part of the container is formed of a PBT-containing resin, the kind of resin forming the other part is not particularly limited, and at least 1 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 may be contained as a constituent component.
In the present invention, the shape of the PBT-containing resin container is not particularly limited, and the capacity of the container to be stored therein is not particularly limited. For example, the container may be a container capable of storing an internal volume of 0.1 to 50ml, preferably 2 to 40ml, and more preferably 4 to 25ml, as a usual eye drop or contact lens wetting solution. The PBT-containing resin container may have a capacity of 40ml to 600ml for containing therein an eye lotion or a contact lens care solution.
The PBT-containing resin container of the present invention may be a container capable of storing an ophthalmic aqueous composition for use in a contact lens.
The ophthalmic aqueous composition used in the present invention may be a multi-dose type containing a plurality of doses, or a single dose type containing a single dose.
In the present invention, the PBT-containing resin container is preferably an eye drop container, an eye lotion container, a contact lens wetting solution container, a contact lens care solution container (including a contact lens cleaning solution container, a contact lens preserving solution container, a contact lens disinfecting solution container, a contact lens multipurpose solution container, and the like), or a contact lens packaging solution container. Particularly preferred are an eye drop container, a contact lens wetting liquid container, and a contact lens care liquid container. The contact lenses referred to herein are all contact lenses, and may be either soft or hard contact lenses.
The present invention also provides a product in a state in which an ophthalmic aqueous composition is contained in a PBT-containing resin container. The present invention also provides an ophthalmic solution, and a contact lens application product, which are contained in the ophthalmic aqueous composition container.
The PBT-containing resin in the PBT-containing resin container of the present invention contains a polymer obtained by a known polymerization method such as polycondensation of terephthalic acid or an ester-forming derivative thereof with 1, 4-butanediol. Additives such as stabilizers may be added to the polymer to prepare a PBT-containing resin. The PBT-containing resin commercially available as the PBT-containing resin can be used without particular limitation. Examples thereof include "Novaduran (registered trademark) 5010R 5" manufactured by Mitsubishi engineering plastics corporation. The polymer synthesized by polycondensation of terephthalic acid or an ester-forming derivative thereof and 1, 4-butanediol may contain any other monomer as a constituent component, and further, may contain other polymer. Other polymers include, but are not limited to, polycarbonate, (meth) acrylic polymers, Polystyrene (PS), polyethylene naphthalate (PEN), polyethylene terephthalate (PET), Polyethylene (PE), polyarylate, polypropylene (PP), and the like. Although not limited thereto, dimethyl terephthalate and the like are exemplified as the ester-forming derivative of terephthalic acid. The PBT-containing resin of the present invention is preferably a resin synthesized by polycondensation of terephthalic acid or an ester-forming derivative thereof and 1, 4-butanediol, in which the content of the polymer component constituting the resin is 50% by weight or more, more preferably 60% by weight or more, and still more preferably 70% by weight or more. Commercially available products may be used.
The PBT-containing resin of the present invention also includes a resin reinforced by further including a reinforcing agent such as glass fiber.
The ophthalmic aqueous composition of the present invention preferably contains, in addition to the component (a) and the component (B), other components which are generally used in ophthalmic aqueous compositions. The component is not particularly limited, and sodium edetate is particularly preferable from the viewpoint of more remarkably obtaining the effect of the present invention. In the present invention, commercially available sodium edetate can be used.
In the ophthalmic aqueous composition of the present invention, from the viewpoint of more remarkably obtaining the effect of the present invention, the total content of edetate sodium is preferably 0.0001 w/v% or more, more preferably 0.0005 w/v% or more, and further preferably 0.001 w/v% or more, relative to the total amount of the ophthalmic aqueous composition. The total content of edetate sodium is preferably 1 w/v% or less, more preferably 0.5 w/v% or less, and still more preferably 0.2 w/v% or less, with respect to the total amount of the ophthalmic aqueous composition. The ratio of the total content of sodium edetate to the total content of component (A) is preferably 0.0001 to 1000 parts by weight, more preferably 0.0005 to 500 parts by weight, and still more preferably 0.001 to 200 parts by weight, based on 1 part by weight of the total content of component (A).
For example, active ingredients in ophthalmic drugs described in the standard 2012 edition of the over-the-counter drug manufacturing (import) approval standard (reviewed by the society of general society, regulation Science) can be exemplified. Specifically, the following components can be mentioned.
An antihistamine: chlorpheniramine maleate
Anti-allergic agent: azailast, amlexanox, ibudilast, levocabastine hydrochloride, cromolyn sodium, pemirolast potassium, olopatadine hydrochloride, and the like.
Decongestants: tetrahydrozoline hydrochloride, naphazoline nitrate, epinephrine hydrochloride, ephedrine hydrochloride, phenylephrine hydrochloride, methylephedrine hydrochloride, and the like.
Amino acids: potassium aspartate, magnesium aspartate, aminoethylsulfonic acid, and the like.
Anti-inflammatory agents: dipotassium glycyrrhizinate, lysozyme chloride, pranoprofen, bromfenac, ketorolac tromethamine, nepafenac and the like.
Astringents: zinc white, zinc lactate, and the like.
And (3) the other: sulfanylisoOxazole, sodium sulfadimidine, neostigmine methylsulfate, cinchocaine, and the like.
Further, the ophthalmic aqueous composition of the present invention may contain an appropriate amount of at least 1 selected from the group consisting of carriers, thickeners, pH adjusters, general saccharides, general tonicity agents, perfumes, cooling agents, chelating agents and other additives. Examples of such additives include various additives described in pharmaceutical additives dictionary 2007 (edited by japan pharmaceutical additives society). Typical examples of the component include the following additives.
Carrier: water, aqueous ethanol, and other aqueous vehicles.
Tackifier: hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, and the like.
Sugar alcohols: xylitol, sorbitol, and the like. They may be any of d-, l-or dl-isomer.
A tonicity agent: aminoethylsulfonic acid, polyethylene glycol, sodium bisulfite, sodium sulfite, potassium chloride, calcium chloride, sodium chloride, magnesium chloride, etc.
pH regulator: hydrochloric acid, acetic acid, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, triethanolamine, monoethanolamine, diisopropanolamine, and the like.
A stabilizer: dibutyl hydroxy toluene, sodium formaldehyde sulfoxylate (rongalite), sodium bisulfite, sodium metabisulfite, monoethanolamine, aluminum monostearate, glycerin monostearate, cyclodextrin, dextran, etc.
Chelating agent: succinic acid, trihydroxymethyl aminomethane, nitrilotriacetic acid, 1-hydroxyethane-1, 1-diphosphonic acid, polyphosphoric acid, metaphosphoric acid, hexametaphosphoric acid, and the like.
Flavor or cooling agent: menthol, camphor, borneol, geraniol, cineole, citronellol, carvone, anethole, eugenol, cineole, limonene, linalyl acetate, borneol, menthone and the like. These may be d-, l-or dl-isomers, and may be blended as essential oils (peppermint oil, mentha piperita oil, spearmint oil, peppermint oil, anise oil, cinnamon oil, rose oil, etc.).
Preservatives other than chlorhexidine, sorbic acid and their salts: dibutylhydroxytoluene, butylhydroxyanisole, alkyldiaminoethylglycine hydrochloride, sodium benzoate, ethanol, tyloxapol, benzalkonium chloride, benzethonium chloride, zinc chloride, chlorobutanol, sodium dehydroacetate, methylparaben, ethylparaben, propylparaben, butylparaben, hydroxyquinoline sulfate, phenethyl alcohol, benzyl alcohol, biguanide compounds (specifically, polyhexamethylene biguanide hydrochloride, etc.), poliomyl chloride, chlorocresol, parachlorometaxylenol, curogel (グローキル) (trade name of Rhodia corporation), and the like.
The water used in the ophthalmic aqueous composition of the present invention may be any physiologically or pharmaceutically acceptable water. Examples of such water include distilled water, normal water, pure water, sterile pure water, water for injection, and distilled water for injection. These definitions are based on the sixteenth corrected japanese pharmacopoeia.
In the present invention, the "salt" includes, for example, alkali metal salts, alkaline earth metal salts, and the like, and basic salts such as salts with inorganic bases, salts with organic bases, and the like, and examples thereof include sodium, potassium, calcium, magnesium, ammonium, or salts with diethanolamine, ethylenediamine, and the like. These salts can be obtained by converting a sulfate group or a carboxyl group present in liranaftate or the like into a salt by a known method. Further, there may be mentioned salts of amines such as ammonia, methylamine, dimethylamine, trimethylamine, dicyclohexylamine, tris (hydroxymethyl) aminomethane, 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, -hydroxylysine, and arginine. In the present invention, the "salt" includes acidic salts and the like, and examples thereof include salts with inorganic acids such as salts of inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like; 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, and the like; or salts with acidic amino acids such as aspartic acid and glutamic acid.
The "physiologically or pharmaceutically acceptable salt" as used herein may also include a solvate or hydrate of the salt.
The form of the ophthalmic aqueous composition of the present invention may be any form as long as it contains water, and for example, it may be any of an aqueous solution, a gel, a suspension, and an emulsion, and is preferably 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, -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 bicarbonate and water; an ophthalmic aqueous composition comprising 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, aminocaproic acid, and water; an ophthalmic aqueous composition containing sodium chondroitin sulfate, sodium hydrogen phosphate, and water; an ophthalmic aqueous composition containing sodium chondroitin sulfate, sodium citrate, and water; an ophthalmic aqueous composition containing 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 containing glucose, boric acid, and water; an ophthalmic aqueous composition containing glucose, -aminocaproic acid, and water; an ophthalmic aqueous composition containing glucose, sodium hydrogen phosphate, and water; an ophthalmic aqueous composition containing glucose, sodium citrate, and water; an ophthalmic aqueous composition containing glucose, sodium bicarbonate, and water; 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, and is, for example, 3 or more, preferably 4 or more, more preferably 5 or more, further preferably 5.5 or more, and still further preferably 6 or more. The pH is 9 or less, preferably 8.5 or less, more preferably 8 or less, still more preferably 7.5 or less, and still more preferably 7 or less.
The osmotic pressure ratio of the ophthalmic aqueous composition of the present invention is suitably set in accordance with the kind and content of the components to be blended, the use of the ophthalmic aqueous composition, the form of the preparation, the method of use, and the like, and is, for example, 0.4 to 5, preferably 0.5 to 4, more preferably 0.6 to 3, and further preferably 0.7 to 2, as long as the osmotic pressure ratio is within a physiologically or pharmaceutically acceptable range. In the ophthalmic aqueous composition of the present invention, the osmotic pressure ratio is determined as an osmotic pressure ratio to physiological saline based on an osmotic pressure measurement method (osmolarity measurement method) according to the sixteenth modified japanese pharmacopoeia.
The viscosity of the ophthalmic aqueous composition of the present invention may be appropriately set depending on the kind and content of the components to be blended, the use of the ophthalmic aqueous composition, the form of the preparation, the method of use, and the like, as long as the viscosity is within a physiologically or pharmaceutically acceptable range. The viscosity at 20 ℃ measured with a rotary viscometer (RE550 type viscometer, manufactured by Toyobo industries Co., Ltd., spindle; 1 ℃ 34' XR 24) is preferably 0.01 to 10000 mPas, more preferably 0.05 to 8000 mPas.
The method of using the ophthalmic aqueous composition of the present invention can be set appropriately depending on the kind and content of the components to be blended, the use of the ophthalmic aqueous composition, and the form of the preparation.
The aqueous ophthalmic composition of the present invention can also inhibit the deterioration of a PBT-containing resin container, and therefore can be used as a deterioration inhibitor for a PBT-containing resin container.
Here, although not limited thereto, the suppression of the deterioration of the PBT-containing resin container means that the properties of the container are less changed even after the container is used or stored for a certain period of time after the ophthalmic aqueous composition is stored. For example, this means that the weight change is small. From the viewpoint of suppressing deterioration, the more suppression of the weight change is better. When an aqueous ophthalmic composition is contained in a PBT-containing resin container, the following problems occur: the PBT-containing resin undergoes a weight change, and the strength, cracks, deformation, and sealability of the container are reduced. That is, when a container made of a PBT-containing resin is used while a drug such as an ophthalmic aqueous composition is stored for a certain period of time, the problem of the change in the properties of the PBT-containing resin container becomes more serious.
The aqueous ophthalmic composition of the present invention can also improve the liquid repellency of the PBT-containing resin container and suppress the remaining of liquid in the container, and therefore can be used as an agent for improving the liquid repellency of a PBT-containing resin container.
Here, the lyophobicity improver for the PBT-containing resin container includes, but is not limited to, a case where the ophthalmic aqueous composition is difficult to wet the container. As described above, as an index indicating that the ophthalmic aqueous composition is difficult to wet with respect to the container, for example, the index can be expressed by the magnitude of the advancing contact angle which is a dynamic contact angle. The larger the advancing contact angle, the more difficult the wetting, indicating a good lyophobic property, and the smaller the advancing contact angle or the larger the absolute value of the negative value, the more easy the wetting, and the poor lyophobic property.
The ophthalmic aqueous composition of the present invention is provided in a form of a single container or a kit in a container containing a PBT resin. When the ophthalmic aqueous composition of the present invention is contained therein, the PBT-containing resin container can be favorably held, and as a result, the properties of the ophthalmic aqueous composition are favorably maintained even after long-term storage.
The ophthalmic aqueous composition of the present invention is prepared by adding the above-mentioned component (a) and component (B) and, if necessary, other components to a carrier in a desired content by a known preparation method. For example, the compound can be produced by a method described in the sixteenth revised Japanese pharmacopoeia general guidelines for pharmaceutical preparations. Specifically, for example, it can be prepared by: the above components are dissolved or suspended in pure water, adjusted to a predetermined pH and osmotic pressure, and sterilized by a known sterilization method.
Examples
The present invention will be described in more detail with reference to examples, but the present invention is not limited to the following examples.
< evaluation of weight Change 1 >
(example 1)
An ophthalmic aqueous composition was prepared by dissolving sodium hyaluronate (weight average molecular weight 85 to 160 ten thousand) as component (a), boric acid and borax as component (B) in pure water at about 70 ℃ to give the concentrations shown in table 2, respectively. The pH was measured at room temperature using a HORIBA pH meter.
(examples 2 to 3)
Ophthalmic aqueous compositions of examples 2 and 3 shown in table 2 were prepared in the same manner as in example 1.
Comparative examples 1 to 3
Aqueous ophthalmic compositions of comparative examples 1 to 3 shown in Table 2 were prepared in the same manner as in example 1.
[ Table 2]
(test method)
Each 3mL of the test solutions of examples 1 to 3 and comparative examples 1 to 3 was filled in a 10mL capacity transparent glass vial (septum cap), and 1 PBT-containing resin (product name: PBTNatural, manufactured by Alam) sheet having a diameter of about 1.0cm, a weight of about 205mg, and a thickness of about 2.0mm was immersed in each of the 1, to seal the vial rapidly. After the resin was allowed to stand at 70 ℃ for 2 weeks in a thermostatic bath, the weight of each resin was measured, and the change in weight per unit volume was calculated from formula 1. This heat treatment corresponds to storage at room temperature for about 3 years. The evaluation can also be made as a change in weight from the initial weight. The volume of the PBT-containing resin can also be calculated from the density and weight of the resin.
(formula 1) weight change per unit volume (mg/cm)3)＝
(resin sheet weight after Heat treatment-resin sheet weight before Heat treatment)/resin volume
The results of the tests carried out in this way are shown in the lower column of table 2.
Further, the results are shown in the figure as shown in fig. 1.
As shown in table 2 and fig. 1, in comparative example 1 in which the PBT-containing resin sheet was immersed in pure water, the weight increase of the PBT-containing resin sheet was observed as compared with that before the heat treatment, but in comparative examples 2 and 3 in which sodium hyaluronate was an acidic polysaccharide and glucose was a monosaccharide, the weight increase of the PBT-containing resin sheet was confirmed to be greater than that of pure water. However, in examples 1 to 3 in which boric acid and borax were added, the weight change per unit volume of the PBT resin was suppressed as compared with that in the case of pure water alone (comparative example 1). Thus, it was confirmed that boric acid and borax suppress the weight change of the PBT-containing resin due to the ophthalmic aqueous composition containing 1 or more selected from acidic polysaccharides and monosaccharides, and suppress the deterioration of the PBT-containing resin associated therewith. The mechanism of action is not clear, but it is considered that the hydrogen ions of the aqueous ophthalmic composition exert some influence on the chain molecular structure of the PBT-containing resin by the buffering ability of the component (B).
< evaluation of weight Change 2 >
(examples 4 to 10)
Ophthalmic aqueous compositions shown in tables 3 to 6 were prepared. The pH was measured at room temperature using a HORIBA pH meter.
Comparative examples 4 to 12
Aqueous ophthalmic compositions of comparative examples 4 to 12 shown in tables 3 to 6 were prepared in the same manner as in examples 4 to 10.
[ Table 3]
[ Table 4]
[ Table 5]
[ Table 6]
(test method)
Each 3mL of the test solutions of examples 4 to 10 and comparative examples 4 to 12 was filled in a 10mL capacity transparent glass vial (septum cap), and 1 PBT-containing resin (product name: PBTNatural, manufactured by Alam) sheet having a diameter of about 1.0cm, a weight of about 205mg, and a thickness of about 2.0mm was immersed in each of the filled sheets and rapidly sealed. After the resin was allowed to stand at 70 ℃ for 2 weeks in a thermostatic bath, the weight of each resin was measured, and the change in weight per unit volume was calculated from formula 1. The evaluation can also be made as a change in weight from the initial weight. The volume of the PBT-containing resin can also be calculated from the density and weight of the resin.
(formula 1) weight change per unit volume (mg/cm)3)＝
(resin sheet weight after Heat treatment-resin sheet weight before Heat treatment)/resin volume
The results of the tests carried out in this way are shown in the lower columns of tables 3 to 6.
As shown in the table, in each comparative example, an increase in weight of the PBT-containing resin sheet was observed as compared with that before the heat treatment. However, in the examples to which boric acid, borax was added, the weight change per unit volume of the PBT-containing resin was suppressed as compared with the comparative examples. Thus, it was confirmed that boric acid and borax suppress the weight change of the PBT-containing resin due to the ophthalmic aqueous composition containing the component (a), and the deterioration of the PBT-containing resin associated therewith is suppressed. The mechanism of action is not clear, but it is considered that the hydrogen ions of the aqueous ophthalmic composition exert some influence on the chain molecular structure of the PBT-containing resin by the buffering ability of the component (B).
< evaluation of weight Change 3 >
(examples 11 to 18)
Ophthalmic aqueous compositions were prepared so as to have concentrations shown in tables 7 to 13. The pH was measured at room temperature using a HORIBA pH meter.
Comparative examples 13 to 22
Ophthalmic aqueous compositions of comparative examples 13 to 22 shown in tables 7 to 13 were prepared in the same manner as in examples 11 to 18.
[ Table 7]
[ Table 8]
[ Table 9]
[ Table 10]
[ Table 11]
[ Table 12]
[ Table 13]
(test method)
Each 2mL of the test solutions of examples and comparative examples was filled in a 10mL capacity transparent glass vial (septum cap), and 1 PBT-containing resin (product name: PBT Natural, manufactured by Alam) sheet having a diameter of about 1.0cm, a weight of about 205mg, and a thickness of about 2.0mm was immersed in each of the 1, and rapidly sealed. After the resin was allowed to stand still at 75 ℃ for 1 week in a thermostatic bath, the weight of each resin was measured, and the change in weight per unit volume was calculated from formula 1. The evaluation can also be made as a change in weight from the initial weight. The volume of the PBT-containing resin can also be calculated from the density and weight of the resin.
(formula 1) weight change per unit volume (mg/cm)3)＝
(resin sheet weight after Heat treatment-resin sheet weight before Heat treatment)/resin volume
The results of the tests carried out in this way are shown in the lower columns of tables 7 to 13.
As shown in the table, in each comparative example, an increase in weight of the PBT-containing resin sheet was observed as compared with that before the heat treatment. However, in the examples to which the buffer was added, the weight change per unit volume of the PBT-containing resin was suppressed as compared with the comparative examples. Thus, it was confirmed that the buffer suppresses the weight change of the PBT-containing resin due to the ophthalmic aqueous composition containing the component (a), and suppresses the deterioration of the PBT-containing resin associated therewith. The mechanism of action is not clear, but it is considered that the hydrogen ions of the aqueous ophthalmic composition exert some influence on the chain molecular structure of the PBT-containing resin by the buffering ability of the component (B).
< evaluation of advancing contact Angle 1 >
Example 19 to 87
Ophthalmic aqueous compositions shown in tables 14 to 32 were prepared by a usual method to prepare test solutions. The advancing contact angle, which is the contact angle when the interface between a solid and a liquid moves, was measured by the same measurement method of the expansion/contraction method of the measurement apparatus using a contact angle meter DM-501 manufactured by synergetics. Specifically, a plate-like PBT-containing resin (product name: PBT Natural, manufactured by Alam corporation) having a regular square column with 1 side of 50mm and a thickness of about 2mm was placed on a stage of a contact angle meter, and the test solution was placed in a dispenser. A1. mu.L drop of the test solution was dropped on a PBT-containing resin plate to form a hemispherical shape. Then, the process is carried out. The tip of the liquid ejecting portion of the dispenser is quickly dropped onto the upper portion of the hemisphere. In this state, the test liquid was continuously discharged at a discharge speed of 6 μ L/sec, and the shape of the liquid droplet was imaged 15 times every 0.1 sec from the side surface. In order to match the measurement conditions of the corresponding comparative examples with those of the examples, the measurement was continued at the same room temperature, and the same plate-like PBT-containing resin was used. Next, the contact angle on the left and right sides of each image was obtained using the analysis software FAMAS of the same measurement apparatus. Here, the contact angle is an angle on the side including the test liquid, out of angles formed by a tangent drawn to the test liquid and a tangent drawn to the surface of the PBT-containing resin plate, from the contact point P of the surface of the PBT-containing resin plate, the test liquid, and air. As the test liquid is discharged, the liquid droplet expands, the contact angle changes, and then, a substantially constant behavior is shown. Therefore, when the average values of the left and right contact angles of each image are calculated and 5 consecutive contact angles are selected by arranging the average values of the left and right contact angles in the order of the captured images, the initial contact angle at which the standard deviation of the average values of the 5 consecutive contact angles is initially 2.5 ° or less is defined as the advancing contact angle of the present invention. The advancing contact angle was obtained by performing these operations 3 times for each test liquid, and the average value of the 3 times was defined as the advancing contact angle of the test liquid. When the advancing contact angle does not change during the liquid droplet expansion, the initial contact angle at which the standard deviation of the average values of 5 consecutive contact angles of the average values of the left and right contact angles is initially 2.5 ° or less is also set as the advancing contact angle of the present invention. The rate of increase of advancing contact angle of the example with respect to advancing contact angle of the corresponding comparative example was calculated from the following formula (2).
< formula (2) > rate of increase (%) { (advancing contact angle of each test liquid/advancing contact angle of comparative example) -1} × 100
The comparative example refers to an ophthalmic aqueous composition excluding the component (B) contained in the examples. For example, example 19 in Table 14 is a comparative example of an ophthalmic aqueous composition containing 0.5 w/v% of sodium chondroitin sulfate and adjusted to the same pH as in example 19, that is, pH5.1 by hydrochloric acid or sodium hydroxide.
Further, unless otherwise noted in the table, the test was carried out immediately after the preparation of the test solutions.
[ 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) Citric acid sodium salt - - 0.1
(B) ε Aminocaproic acid - - 3
Hydrochloric acid Proper amount of Proper amount of Proper amount of
Sodium hydroxide Proper amount of Proper amount of Proper amount of
Pure water The remaining part The remaining part The remaining part
Total up to 100 100 100
pH 6.9 5.2 7.0
Rate of rise 12.4％ 10.4％ 10.1％
[ Table 16]
[ Table 17]
[ Table 18]
Examples 41 to 45 and comparative examples corresponding thereto were used for the test with a liquid heat-treated at 80 ℃ for 1 day.
[ Table 19]
[ Table 20]
[ Table 21]
[ Table 22]
[ Table 23]
[ Table 24]
[ Table 25]
[ Table 26]
Example 68 and the corresponding comparative examples a liquid heat-treated at 75 ℃ for 3 days was used for the test.
[ Table 27]
[ Table 28]
[ Table 29]
[ Table 30]
[ Table 31]
[ Table 32]
In example 87 and comparative example, a liquid heat-treated at 75 ℃ for 3 days was used for the test.
As shown in the tables, the rate of increase in the examples was higher than that in the comparative examples containing no component (B). Thus, it was confirmed that an aqueous ophthalmic composition containing component (B) in an aqueous ophthalmic composition containing component (A) hardly wets a PBT-containing resin during exercise. It is found that the PBT-containing resin exhibits an advantageous effect such as an improvement in liquid repellency.
< evaluation of weight Change 4 >
(examples 88 to 122)
Ophthalmic aqueous compositions were prepared by adding the components (A), (B) and other components shown in tables 33 to 53 at the concentrations shown in the tables. The pH was measured at room temperature using a HORIBA pH meter.
Comparative examples 23 to 63
Aqueous ophthalmic compositions of comparative examples shown in tables 33 to 53 were prepared in the same manner as in the examples.
(test method)
Each 3mL of the test solutions of examples and comparative examples was filled in a 10mL capacity transparent glass vial (septum cap), and 1 PBT-containing resin (product name: PBT Natural, manufactured by Alam) sheet having a diameter of about 1.0cm, a weight of about 205mg, and a thickness of about 2.0mm was immersed in each of the 1, and rapidly sealed. After the heat treatment was performed by leaving the resin in a constant temperature bath at the temperatures shown in the tables and the days, the weight of each resin was measured, and the change in weight per unit volume was calculated from formula 1. The evaluation can also be made as a change in weight from the initial weight. The volume of the PBT-containing resin can also be calculated from the density and weight of the resin.
(formula 1) weight change per unit volume (mg/cm)3)＝
(resin sheet weight after Heat treatment-resin sheet weight before Heat treatment)/resin volume
The results of the tests carried out in this way are shown in the lower column of the respective tables.
[ Table 33]
The heat treatment of comparative examples 23, 24 and examples 88, 89 was allowed to stand at 50 ℃ for 7 days.
[ Table 34]
The heat treatment of comparative examples 25 to 27 and examples 90 and 91 was allowed to stand at 75 ℃ for 3 days.
[ Table 35]
The heat treatments of comparative examples 28, 29 and example 92 were left standing at 50 ℃ for 12 days.
[ Table 36]
The heat treatment of comparative examples 30, 31 and example 93 was allowed to stand at 50 ℃ for 17 days.
[ Table 37]
The heat treatments of comparative examples 23, 32 and example 94 were left standing at 50 ℃ for 7 days.
[ Table 38]
The heat treatment of comparative examples 33, 34 and example 95 was left standing at 50 ℃ for 12 days.
[ Table 39]
The heat treatments of comparative examples 23, 35 to 37 and examples 96 to 100 were allowed to stand at 50 ℃ for 7 days.
[ Table 40]
The heat treatment of comparative examples 23, 38 and example 101 was left standing at 50 ℃ for 7 days.
[ Table 41]
The heat treatment of comparative examples 39, 40 and example 102 was left standing at 50 ℃ for 7 days.
[ Table 42]
The heat treatment of comparative examples 41 to 43 and examples 103 and 104 was allowed to stand at 50 ℃ for 12 days.
[ Table 43]
The heat treatment of comparative examples 44, 45 and example 105 was left standing at 75 ℃ for 3 days.
[ Table 44]
The heat treatment of comparative examples 33, 46 and 47 and examples 106 and 107 were allowed to stand at 50 ℃ for 12 days.
[ Table 45]
The heat treatments of comparative examples 23, 48 to 50 and examples 108 to 110 were allowed to stand at 50 ℃ for 7 days.
[ Table 46]
The heat treatment of comparative examples 33, 51, 52 and examples 111, 112 was left standing at 50 ℃ for 12 days.
[ Table 47]
The heat treatment of comparative examples 23, 53 and 54 and examples 113 and 114 was allowed to stand at 50 ℃ for 7 days.
[ Table 48]
The heat treatment of comparative examples 33, 55 and example 115 was left standing at 50 ℃ for 12 days.
[ Table 49]
The heat treatment of comparative examples 56, 57 and example 116 was allowed to stand at 50 ℃ for 7 days.
[ Table 50]
The heat treatment of comparative examples 39, 58 and example 117 was left standing at 50 ℃ for 7 days.
[ Table 51]
The heat treatment of comparative examples 30, 59, and 60 and examples 118 and 119 was allowed to stand at 50 ℃ for 17 days.
[ Table 52]
The heat treatment of comparative examples 39, 61 and example 120 was left standing at 50 ℃ for 7 days.
[ Table 53]
The heat treatment of comparative examples 23, 62, 63 and examples 121, 122 was left standing at 50 ℃ for 7 days.
< preparation of ophthalmic Water-based composition and Container storage case >
Ophthalmic aqueous compositions of the following tables 54 to 57 (tables 56 and 57 are up to 2 pages, respectively) were prepared. Preparation examples 2, 3, 6, 9, 10, 15, and 18 to 21 were filled in a container body portion made of a PET-containing resin, a PBT-containing resin-made hole plug was attached to an opening portion of the body portion, and a PP-containing resin-made cap was closed. The containers of formulation examples 7 to 8 were filled in the main body of the container made of a PP-containing resin, the opening of the main body was fitted with a hole plug made of a PBT-containing resin, and the container was covered with a cap made of an ABS resin. Formulations 4 and 14 were filled in a container body made of an ethylene-vinyl acetate copolymer-containing resin, and a cap made of a PE resin was attached to an opening of the body by fitting a hole plug made of a PBT resin. Formulation examples 1, 5 and 17 were filled in a container body made of PBT-containing resin, a hole plug made of PE-containing resin was attached to an opening of the body, and a cap made of PS-containing resin was applied. Preparation examples 11, 13 and 16 were filled in a container main body portion made of a PE-containing resin, a PBT-containing resin open-hole plug was attached to an opening portion of the main body portion, and a PP-containing resin cap was attached. Formulation example 12 was filled in a container containing PBT resin in which the main body and the opening of the ophthalmic aqueous composition were the same, and a cap containing PP resin was closed. The unit of the numerical value in the formulation example is "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
Glycyrrhizic acid dipotassium salt 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 salt 0.05 0.05 0.5 0.5 0.05
L-aspartic acid potassium salt 1 1 1
Amino ethyl sulfonic 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
d 1-Camphor 0.02
d-borneol 0.001 0.01 0.02 0.005
Geraniol 0.001
Hyaluronic acid sodium salt 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
Polyhexamethylene guanidine hydrochloride 0.001
Benzalkonium chloride 0.02 0.01 0.005
Phenylethanolic acid 0.05
Chlorobutanol 0.05 0.2 0.2 0.1
Edetic acid sodium salt 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
Citric acid sodium salt .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 Eye lotion
Chlorpheniramine maleate 0.003
Glycyrrhizic acid dipotassium salt 0.025
Zinc sulfate 0.01
Pyridoxine hydrochloride 0.01
Cyanocobalamin 0.001
Tocopheryl acetate 0.005
Chondroitin sulfate sodium salt 0.5 0.05 0.05
L-aspartic acidPotassium salt 0.5 0.1
Amino ethyl sulfonic acid 0.02
1-menthol 0.005 0.02 0.05
d-camphor 0.01
d 1-Camphor 0.08
d-borneol 0.005 0.002
Geraniol 0.005 0.008
Hyaluronic acid sodium salt 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
Polyhexamethylene guanidine hydrochloride 0.0001
Chlorhexidine gluconate 0.005
Chlorobutanol 0.3
Edetic acid sodium salt 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
Poloxamers 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 (6)

1. An aqueous ophthalmic composition comprising (B) a buffer and (A) 1 or more selected from the group consisting of: polysaccharides; a monosaccharide; selected from vitamin B12Vitamin B, vitamin C21 or more vitamins selected from the group consisting of retinoids, and panthenol; 1 or more kinds of oil components selected from vegetable oil, animal oil, and mineral oil; 1 or more surfactants selected from polyoxyethylene castor oil, polyoxyethylene hardened castor oil, polyoxyethylene polyoxypropylene glycol, and polyoxyl stearate; selected from tranilast, ketotifen, diphenhydramine, and mixtures thereofAnd salts thereof, 1 or more antiallergic components; 1 or more preservatives selected from chlorhexidine, sorbic acid, and salts thereof; 1 or more thickening components selected from the group consisting of carboxymethyl cellulose, methyl cellulose, vinyl polymer compounds, and salts thereof; a polyol; 1 or more antiinflammatory components selected from berberine, azulene sulfonic acid, allantoin, zinc sulfate, and their salts; selected from the group consisting of sulfamethoxazole1 or more antibacterial agents selected from oxazole and salts thereof; 1 or more of 1 or more cooling agents selected from eucalyptus oil and bergamot oil,
the ophthalmic aqueous composition is contained in a container (C) in which a part or the whole of the surface in contact with the ophthalmic aqueous composition is molded with a resin containing polybutylene terephthalate.
2. An ophthalmic aqueous composition according to claim 1, wherein in the component (a), the polysaccharide is at least 1 selected from alginic acid, gellan gum, xanthan gum, hyaluronic acid, chondroitin sulfate, and salts thereof; the monosaccharide is glucose; vitamins are selected from cyanocobalamin, retinol, panthenol, flavin adenine dinucleotide, and 1 or more of their salts; the oil component is selected from more than 1 of oleum Sesami, oleum ricini, lanolin, vaseline, and liquid paraffin; the surfactant is more than 1 selected from polyoxyethylene castor oil, polyoxyethylene hardened castor oil, polyoxyethylene polyoxypropylene glycol and polyoxyl stearate; the antiallergic component is more than 1 selected from tranilast, ketotifen fumarate, and diphenhydramine hydrochloride; the antiseptic is more than 1 selected from chlorhexidine gluconate and potassium sorbate; the thickening component is at least 1 selected from carboxymethyl cellulose, methyl cellulose, polyvinylpyrrolidone, carboxyvinyl polymer, and their salts; the polyhydric alcohol is more than 1 selected from propylene glycol, glycerol and mannitol; the anti-inflammatory component is selected from berberine chloride, sodium azulene sulfonate, allantoin, and sulfurMore than 1 of zinc; the antibacterial agent is sulfamethoxazoleSodium oxazole; the cooling agent is more than 1 selected from oleum Eucalypti and bergamot oil.
3. An ophthalmic aqueous composition according to claim 1 or 2, further comprising edetate sodium.
4. A method for imparting an effect of suppressing a change in weight of a polybutylene terephthalate-containing resin container to an aqueous composition, wherein in the aqueous composition, (B) a buffer and (A) 1 or more selected from the group consisting of: polysaccharides; a monosaccharide; selected from vitamin B12Vitamin B, vitamin C21 or more vitamins selected from the group consisting of retinoids, and panthenol; 1 or more kinds of oil components selected from vegetable oil, animal oil, and mineral oil; 1 or more surfactants selected from polyoxyethylene castor oil, polyoxyethylene hardened castor oil, polyoxyethylene polyoxypropylene glycol, and polyoxyl stearate; 1 or more antiallergic components selected from tranilast, ketotifen, diphenhydramine, and their salts; 1 or more preservatives selected from chlorhexidine, sorbic acid, and salts thereof; 1 or more thickening components selected from the group consisting of carboxymethyl cellulose, methyl cellulose, vinyl polymer compounds, and salts thereof; a polyol; 1 or more antiinflammatory components selected from berberine, azulene sulfonic acid, allantoin, zinc sulfate, and their salts; selected from the group consisting of sulfamethoxazole1 or more antibacterial agents selected from oxazole and salts thereof; 1 or more cooling agents selected from eucalyptus oil and bergamot oil, thereby imparting an effect of suppressing a weight change of the polybutylene terephthalate-containing resin container to the aqueous composition.
5. A method for imparting an effect of suppressing wetting of a polybutylene terephthalate-containing resin container to an aqueous composition, wherein in the aqueous composition, (B) a buffer and (A) 1 or more selected from the group consisting of: polysaccharides; a monosaccharide; selected from vitamin B12Vitamin B, vitamin C21 or more vitamins selected from the group consisting of retinoids, and panthenol; 1 or more kinds of oil components selected from vegetable oil, animal oil, and mineral oil; 1 or more surfactants selected from polyoxyethylene castor oil, polyoxyethylene hardened castor oil, polyoxyethylene polyoxypropylene glycol, and polyoxyl stearate; 1 or more antiallergic components selected from tranilast, ketotifen, diphenhydramine, and their salts; 1 or more preservatives selected from chlorhexidine, sorbic acid, and salts thereof; 1 or more thickening components selected from the group consisting of carboxymethyl cellulose, methyl cellulose, vinyl polymer compounds, and salts thereof; a polyol; 1 or more antiinflammatory components selected from berberine, azulene sulfonic acid, allantoin, zinc sulfate, and their salts; selected from the group consisting of sulfamethoxazole1 or more antibacterial agents selected from oxazole and salts thereof; 1 or more of 1 or more cooling agents selected from eucalyptus oil and bergamot oil, thereby imparting an effect of suppressing wetting of the polybutylene terephthalate-containing resin container to the aqueous composition.
6. A liquid repellency enhancer for an ophthalmic polybutylene terephthalate-containing resin container, comprising (B) a buffer and (A) 1 or more selected from the group consisting of: polysaccharides; a monosaccharide; selected from vitamin B12Vitamin B, vitamin C21 or more vitamins selected from the group consisting of retinoids, and panthenol; 1 or more kinds of oil components selected from vegetable oil, animal oil, and mineral oil; 1 or more surfactants selected from polyoxyethylene castor oil, polyoxyethylene hardened castor oil, polyoxyethylene polyoxypropylene glycol, and polyoxyl stearate; selecting1 or more antiallergic components selected from tranilast, ketotifen, diphenhydramine, and their salts; 1 or more preservatives selected from chlorhexidine, sorbic acid, and salts thereof; 1 or more thickening components selected from the group consisting of carboxymethyl cellulose, methyl cellulose, vinyl polymer compounds, and salts thereof; a polyol; 1 or more antiinflammatory components selected from berberine, azulene sulfonic acid, allantoin, zinc sulfate, and their salts; selected from the group consisting of sulfamethoxazole1 or more antibacterial agents selected from oxazole and salts thereof; more than 1 kind of cooling agent selected from oleum Eucalypti and bergamot oil.
HK17106984.6A 2014-06-10 2015-06-09 Aqueous composition for ophthalmic use HK1233184B (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2014-119885 2014-06-10
JP2015-083703 2015-04-15

Publications (2)

Publication Number Publication Date
HK1233184A1 true HK1233184A1 (en) 2018-01-26
HK1233184B HK1233184B (en) 2022-01-07

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