WO2014087931A1 - 水性眼科組成物 - Google Patents
水性眼科組成物 Download PDFInfo
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- WO2014087931A1 WO2014087931A1 PCT/JP2013/082188 JP2013082188W WO2014087931A1 WO 2014087931 A1 WO2014087931 A1 WO 2014087931A1 JP 2013082188 W JP2013082188 W JP 2013082188W WO 2014087931 A1 WO2014087931 A1 WO 2014087931A1
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- ophthalmic composition
- aqueous ophthalmic
- castor oil
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- oil
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
- A01N25/22—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing ingredients stabilising the active ingredients
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
- A01N37/36—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a singly bound oxygen or sulfur atom attached to the same carbon skeleton, this oxygen or sulfur atom not being a member of a carboxylic group or of a thio analogue, or of a derivative thereof, e.g. hydroxy-carboxylic acids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/07—Retinol compounds, e.g. vitamin A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
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- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D1/00—Detergent compositions based essentially on surface-active compounds; Use of these compounds as a detergent
- C11D1/66—Non-ionic compounds
- C11D1/825—Mixtures of compounds all of which are non-ionic
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- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
- C11D3/16—Organic compounds
- C11D3/20—Organic compounds containing oxygen
- C11D3/2003—Alcohols; Phenols
- C11D3/2006—Monohydric alcohols
- C11D3/2037—Terpenes
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
- C11D3/16—Organic compounds
- C11D3/24—Organic compounds containing halogen
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
- C11D3/16—Organic compounds
- C11D3/38—Products with no well-defined composition, e.g. natural products
- C11D3/382—Vegetable products, e.g. soya meal, wood flour, sawdust
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
- C11D3/48—Medical, disinfecting agents, disinfecting, antibacterial, germicidal or antimicrobial compositions
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D1/00—Detergent compositions based essentially on surface-active compounds; Use of these compounds as a detergent
- C11D1/66—Non-ionic compounds
- C11D1/72—Ethers of polyoxyalkylene glycols
- C11D1/721—End blocked ethers
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D1/00—Detergent compositions based essentially on surface-active compounds; Use of these compounds as a detergent
- C11D1/66—Non-ionic compounds
- C11D1/74—Carboxylates or sulfonates esters of polyoxyalkylene glycols
Definitions
- the present invention relates to an aqueous ophthalmic composition. More specifically, the present invention relates to an aqueous ophthalmic composition with reduced foaming and reduced defoaming time.
- solubilizers are blended in many formulations for the purpose of dissolving relatively water-soluble components.
- One of the solubilizing agents used in the ophthalmic field is a surfactant.
- Polyoxyethylene castor oil is a kind of nonionic surfactant and is known to be blended in an aqueous ophthalmic composition for the purpose of assisting dissolution of other blended components (Patent Document 1).
- Polyethylene glycol monostearate is also a kind of nonionic surfactant, and is known to be blended into an aqueous ophthalmic composition for the purpose of assisting dissolution of other blended components.
- an aqueous composition containing a surfactant is likely to foam, and it is inevitable that foam is generated by applying vibration or impact during production or distribution.
- dissolution confirmation and foreign substance inspection in the manufacturing process are essential.
- bubbles are generated in the aqueous ophthalmic composition being manufactured and the rate of disappearance of the bubbles is slow, it is difficult to distinguish foreign substances from the foam, so it takes a long time for the dissolution confirmation and foreign substance inspection processes. Problems such as inefficient production can occur.
- aqueous ophthalmic composition various active ingredients or additives are generally blended depending on the purpose.
- a mucosa-applied composition containing a vegetable oil such as sesame oil or castor oil is disclosed (Patent Document 2).
- Vitamin A has also been included in ophthalmic compositions for the purpose of relieving eye fatigue and exerting anti-inflammatory action by promoting metabolism and respiration of eye cells.
- Patent Document 3 Chlorobutanol is also known as an additive for aqueous ophthalmic compositions.
- the present inventors have found a new problem that an aqueous ophthalmic composition in which polyoxyethylene castor oil and polyethylene glycol monostearate coexist is particularly easy to foam and foam is difficult to disappear.
- the present invention relates to such an aqueous ophthalmic composition that easily foams, and suppresses the generation of bubbles due to vibration or impact, and even if bubbles are generated once, the defoaming time is shortened, etc.
- the purpose is to provide.
- component (A) polyoxyethylene castor oil
- component (A) polyethylene glycol monostearate
- component (B) polyoxyethylene castor oil
- component (C) chlorobutanol
- the present invention provides, for example, the following novel aqueous ophthalmic compositions.
- Item 1-1 An aqueous ophthalmic composition containing at least one selected from the group consisting of (A) polyoxyethylene castor oil, (B) polyethylene glycol monostearate, and (C) sesame oil, castor oil, vitamin A and chlorobutanol.
- Item 1-2 An aqueous ophthalmic composition containing at least one selected from the group consisting of (A) polyoxyethylene castor oil, (B) polyethylene glycol monostearate, and (C) sesame oil, castor oil, vitamin A and chlorobutanol.
- Item 1-2 Item 11.
- Item 1-3 Item 11.
- Item 11. The aqueous solution according to any one of Items 1-1 to 1-5, wherein the content ratio of the component (B) with respect to 1 part by mass of the total component (A) is 0.001 to 100 parts by mass in terms of the total content Ophthalmic composition.
- Item 11 The aqueous ophthalmic composition according to Item 1-10, wherein the content of component (D) is 0.01 to 20 w / v% in total based on the total amount of the aqueous ophthalmic composition.
- aqueous ophthalmic composition according to any one of Items 1-1 to 1-11, wherein the component (E) further contains a surfactant other than the components (A) and (B).
- Item (E) is Item 1-12, wherein the component is at least one selected from the group consisting of polyoxyethylene sorbitan fatty acid ester, polyoxyethylene hydrogenated castor oil, and polyoxyethylene-polyoxypropylene block copolymer.
- Aqueous ophthalmic composition Item 1-14. Item 14.
- this invention provides the method of suppressing foaming in the aqueous ophthalmic composition of the aspect hung up below, for example.
- the aqueous ophthalmic composition contains at least one selected from the group consisting of (A) polyoxyethylene castor oil, (B) polyethylene glycol monostearate, and (C) sesame oil, castor oil, vitamin A and chlorobutanol.
- a method of suppressing foaming in the aqueous ophthalmic composition Item 2-2.
- the aqueous ophthalmic composition containing (A) polyoxyethylene castor oil and (B) polyethylene glycol monostearate contains (C) at least one selected from the group consisting of sesame oil, castor oil, vitamin A and chlorobutanol.
- water-based ophthalmic composition by making.
- this invention provides the method of shortening the foam
- the aqueous ophthalmic composition contains at least one selected from the group consisting of (A) polyoxyethylene castor oil, (B) polyethylene glycol monostearate, and (C) sesame oil, castor oil, vitamin A and chlorobutanol. The method of shortening the defoaming time in this aqueous ophthalmic composition.
- the aqueous ophthalmic composition containing (A) polyoxyethylene castor oil and (B) polyethylene glycol monostearate contains (C) at least one selected from the group consisting of sesame oil, castor oil, vitamin A and chlorobutanol.
- the aqueous ophthalmic composition contains at least one selected from the group consisting of (A) polyoxyethylene castor oil, (B) polyethylene glycol monostearate, and (C) sesame oil, castor oil, vitamin A and chlorobutanol.
- the aqueous ophthalmic composition containing (A) polyoxyethylene castor oil and (B) polyethylene glycol monostearate contains (C) at least one selected from the group consisting of sesame oil, castor oil, vitamin A and chlorobutanol.
- water-based ophthalmic composition contains (C) at least one selected from the group consisting of sesame oil, castor oil, vitamin A and chlorobutanol.
- this invention provides the method of enhancing the preservation
- the aqueous ophthalmic composition contains at least one selected from the group consisting of (A) polyoxyethylene castor oil, (B) polyethylene glycol monostearate, and (C) sesame oil, castor oil, vitamin A and chlorobutanol. Thereby enhancing the storage efficacy of the aqueous ophthalmic composition.
- the present invention provides, for example, a method for imparting a tear stabilizing effect or a method for imparting a tear oil layer extending action to an aqueous ophthalmic composition according to the embodiment described below.
- Item 5-1 (A) polyoxyethylene castor oil, (B) polyethylene glycol monostearate, and (C) at least one selected from the group consisting of sesame oil, castor oil, vitamin A, and chlorobutanol is included in the aqueous ophthalmic composition.
- a method for imparting a tear stabilizing effect to the aqueous ophthalmic composition Item 5-2.
- A polyoxyethylene castor oil
- B polyethylene glycol monostearate
- C at least one selected from the group consisting of sesame oil, castor oil, vitamin A, and chlorobutanol is included in the aqueous ophthalmic composition.
- this invention provides the method of suppressing the odor of the aqueous ophthalmic composition of the aspect hung up below, for example.
- Item 6-1 (A) polyoxyethylene castor oil, (B) polyethylene glycol monostearate, and (C) at least one selected from the group consisting of sesame oil, castor oil, vitamin A, and chlorobutanol is included in the aqueous ophthalmic composition.
- the method of suppressing the odor in this aqueous ophthalmic composition Item 6-2.
- An aqueous ophthalmic composition containing (A) polyoxyethylene castor oil and (B) polyethylene glycol monostearate has (C) at least one selected from the group consisting of sesame oil, castor oil, vitamin A, and chlorobutanol.
- Item 7-1 At least selected from the group consisting of (A) polyoxyethylene castor oil, (B) polyethylene glycol monostearate, and (C) sesame oil, castor oil, vitamin A and chlorobutanol for the manufacture of an aqueous ophthalmic composition.
- Item 7-2 The use according to Item 7-1, wherein the aqueous ophthalmic composition is the composition according to any one of Items 1-1 to 1-18.
- Item 8-1 As an aqueous ophthalmic composition, comprising (A) polyoxyethylene castor oil, (B) polyethylene glycol monostearate, and (C) at least one selected from the group consisting of sesame oil, castor oil, vitamin A and chlorobutanol Use of the composition.
- Item 8-2 As an aqueous ophthalmic composition, comprising (A) polyoxyethylene castor oil, (B) polyethylene glycol monostearate, and (C) at least one selected from the group consisting of sesame oil, castor oil, vitamin A and chlorobutanol Use of the composition.
- Item 8-2 Item 15. The use according to Item 8-1, wherein the composition is the composition according to any one of Items 1-1 to 1-18.
- this invention also provides the composition of the aspect hung up below, for example.
- Item 9-1 Selected from the group consisting of (A) polyoxyethylene castor oil, (B) polyethylene glycol monostearate, and (C) sesame oil, castor oil, vitamin A and chlorobutanol for use as an aqueous ophthalmic composition A composition comprising at least one type.
- Item 9-1 is the composition according to any one of Items 1-1 to 1-18.
- this invention also provides the manufacturing method of the aqueous ophthalmic composition of the aspect hung up below, for example.
- Item 10-1 A step of mixing water, (A) polyoxyethylene castor oil, (B) polyethylene glycol monostearate, and (C) at least one selected from the group consisting of sesame oil, castor oil, vitamin A and chlorobutanol.
- a method for producing an aqueous ophthalmic composition Item 10-2.
- Item 10 The production method according to Item 10-1, wherein the aqueous ophthalmic composition is the composition according to any one of Items 1-1 to 1-18.
- the aqueous ophthalmic composition contains polyoxyethylene castor oil, polyethylene glycol monostearate, and at least one selected from the group consisting of sesame oil, castor oil, vitamin A, and chlorobutanol.
- the occurrence of bubbles in the aqueous ophthalmic composition is suppressed, variation in the amount of each use at the time of use can be suppressed, and in particular, an eye drop or contact lens mounting liquid with a relatively small amount of use at one time. In this case, it is easy for the user himself to control the amount of use for each time and to handle it. Therefore, the compliance is improved, and is particularly useful when the aqueous ophthalmic composition is a pharmaceutical product.
- the aqueous ophthalmic composition of the present invention exhibits, as another effect, a remarkable tear film stabilizing effect, that is, a tear film stabilizing effect. Therefore, the aqueous ophthalmic composition of the present invention has an eye drop, an eye wash, a contact lens mounting solution, and a contact which are used for the purpose of suppressing tearing of the tear film and preventing dry eye or eye contact. It is particularly useful as a lens care agent.
- the aqueous ophthalmic composition of the present invention has a remarkable effect of enhancing the preservation efficacy as yet another effect. Therefore, the decay of the aqueous ophthalmic composition due to microbial contamination after opening can be suppressed. Therefore, it is useful as a multi-dose-type aqueous ophthalmic composition that is used repeatedly after opening, and in particular, although high preservation efficacy is desired from the viewpoint of hygiene, eye drops, eyewashes, and contacts are difficult to formulate a large amount of preservatives from the viewpoint of safety. It is particularly useful as a lens mounting solution, a contact lens care agent, and the like.
- an excellent tear oil layer extension effect is exhibited. Therefore, it can diffuse quickly to the corneal surface after instillation without destroying the tear film. Therefore, the oil component contained in the aqueous ophthalmic composition does not form oil droplets on the tear film surface when instilled, but can be rapidly developed as an oil layer. As a result, the effect of suppressing tear evaporation can be obtained more effectively and quickly, and the eye drops, eye wash, contact lens mounting liquid, and contact lens care used for the purpose of suppressing dry eye or eye contact. It is particularly useful for agents.
- an effect of suppressing a specific odor caused by polyoxyethylene castor oil and polyethylene glycol monostearate is also exhibited. Therefore, the user can comfortably use the aqueous ophthalmic composition for a long period of time, and the compliance is improved, which is particularly useful when the aqueous ophthalmic composition is a pharmaceutical product.
- the aqueous ophthalmic composition of the present invention has the various excellent effects described above, and can be used safely and comfortably for a long period of time.
- the aqueous ophthalmic composition of the present invention is at least one selected from the group consisting of (A) polyoxyethylene castor oil, (B) polyethylene glycol monostearate, and (C) sesame oil, castor oil, vitamin A and chlorobutanol. Containing.
- the aqueous ophthalmic composition means an ophthalmic composition having a water content of 40 w / v% or more based on the total amount of the aqueous ophthalmic composition.
- the water content in the aqueous ophthalmic composition is preferably 85 w / v% or more, more preferably 90 w / v% or more, still more preferably 92 w / v% or more, and particularly preferably 95 w / v% or more.
- the unit of content “%” means “w / v%” and is synonymous with “g / 100 mL”.
- POP polyoxypropylene
- the contact lens is meant to include all types of contact lenses such as hard, oxygen-permeable hard, soft (including silicone hydrogel lenses), and color.
- the aqueous ophthalmic composition of the present invention contains polyoxyethylene castor oil (component (A)).
- component (A) polyoxyethylene castor oil
- B polyethylene glycol monostearate
- C sesame oil
- castor oil vitamin A and chlorobutanol
- Polyoxyethylene castor oil is a known compound obtained by addition polymerization of ethylene oxide to castor oil, and several types having different average addition mole numbers of ethylene oxide are known.
- the average added mole number of ethylene oxide in the polyoxyethylene castor oil used as the component (A) is not particularly limited, but is, for example, about 2 to 70 moles.
- polyoxyethylene castor oil 3 having an average addition mole number of ethylene oxide of 3
- polyoxyethylene castor oil 4 having an average addition mole number of ethylene oxide of 4
- polyoxyethylene castor oil 10 with an average addition mole number of ethylene oxide of 10
- Polyoxyethylene castor oil 13.5 having a mole number of 13.5
- polyoxyethylene castor oil 17 having an average addition mole number of ethylene oxide of 17
- polyoxyethylene castor oil having an average addition mole number of ethylene oxide of 20 Oil
- polyoxyethylene castor oil 25 having an average added mole number of ethylene oxide of 25
- polyoxyethylene castor oil 30 having an average addition mole number of 30
- polyoxyethylene castor oil 35 having an average addition mole number of ethylene oxide of 35
- polyoxyethylene castor oil 40 having an average addition mole number of ethylene oxide of 40
- Polyoxyethylene castor oil 3 having an average addition mole number of ethylene oxide of 3
- polyoxyethylene castor oil 4 having an average addition mole number of ethylene oxide of
- the average added mole number of ethylene oxide is 2 to 70, preferably 2 to 40, more preferably 3 to 35, and particularly preferably.
- the average added mole number of ethylene oxide is 2 to 35, preferably 2 to 30, and more preferably 2
- these polyoxyethylene castor oils may be used alone or in any combination of two or more.
- the polyoxyethylene castor oil used by this invention is a compound different from the polyoxyethylene hydrogenated castor oil obtained by addition-polymerizing ethylene oxide to hydrogenated castor oil, and is distinguished from this.
- the content of the component (A) is not particularly limited, and the type of the component (A), the types of the component (B) and the component (C) to be used together and the content thereof, the aqueous ophthalmology It is appropriately set according to the use of the composition, the form of preparation, the method of use and the like.
- the total content of the component (A) is 0.0001 to 5 w / v%, preferably 0.001 to 4 w / v%, more preferably 0. 0.002 to 3 w / v%, more preferably 0.005 to 2 w / v%, particularly preferably 0.01 to 1 w / v%, and most preferably 0.05 to 0.5 w / v%.
- the content of the component (A) is suitable from the viewpoint of further enhancing the tear oil layer extending action, tear fluid stabilizing action, and preservation effect enhancing action. Moreover, if it is content of the said (A) component, the effect
- the aqueous ophthalmic composition of the present invention contains polyethylene glycol monostearate (component (B)) in addition to the component (A).
- component (B) polyethylene glycol monostearate
- component (C) sesame oil, castor oil, vitamin A and chlorobutanol which will be described later, the excellent effects of the present invention described above are exhibited.
- Polyethylene glycol monostearate is a known compound that is also called macrogol stearate, polyethylene glycol stearate or polyoxyl stearate, and several types with different average added mole numbers of ethylene oxide are known.
- the average added mole number of ethylene oxide in the polyoxyl stearate used as the component (B) is about 2 to 150 moles.
- polyoxyl stearate 140 having an average addition mole number of ethylene oxide of 140
- polyoxyl stearate 70 having an average addition mole number of ethylene oxide of 70
- stearic acid having an average addition mole number of ethylene oxide of 55
- Polyoxyl 55 polyoxyl stearate 45 with an average addition mole number of ethylene oxide of 45
- polyoxyl stearate 40 with an average addition mole number of ethylene oxide of 40
- polyoxyl stearate 35 with an average addition mole number of ethylene oxide of 35
- Polyoxyl stearate 30 having an average addition mole number of ethylene oxide
- polyoxyl 25 stearate having an average addition mole number of ethylene oxide of 25
- polyoxyl stearate 23 having an average addition mole number of ethylene oxide of 23, oxidation Average of ethylene
- Polyoxyl stearate 10 having a mole number of 10
- polyoxyl stearate 9 having an average addition mole number of ethylene oxide of 9
- the average added mole number of ethylene oxide is 2 to 150, preferably 2 to 80, more preferably 10 to 70, and even more preferably 10 Mention may be made of polyoxyl stearates of ⁇ 60, particularly preferably 20 ⁇ 60.
- these polyoxyl stearates may be used alone or in any combination of two or more.
- the content of the component (B) in the aqueous ophthalmic composition of the present invention is not particularly limited.
- the type of the component (B), the content of the component (A) and the component (C) to be used together, the content of the aqueous ophthalmic composition It is appropriately set according to the use, formulation form, method of use and the like.
- the total content of the component (B) is 0.0001 to 10 w / v%, preferably 0.0005 to 5 w / v%, more preferably 0 0.001 to 4 w / v%, more preferably 0.005 to 3 w / v%, particularly preferably 0.01 to 2.5 w / v%, and still more preferably 0.05 to 2.5 w / v%.
- the content of the component (B) is preferable from the viewpoint of further enhancing the tear oil layer extending action, tear fluid stabilizing action, and preservation effect enhancing action. Moreover, if it is content of the said (B) component, the effect
- the content ratio of the (B) component to the (A) component is the type of the (A) component and the (B) component, the use of the aqueous ophthalmic composition, the formulation form, the method of use, etc. It is set appropriately according to For example, the content ratio of the component (B) is 0.001 to 1000 parts by mass with respect to 1 part by mass of the total content of the component (A) contained in the aqueous ophthalmic composition of the present invention, preferably 0.005 to 500 parts by mass, more preferably 0.01 to 200 parts by mass, still more preferably 0.05 to 50 parts by mass, particularly preferably 0.1 to 10 parts by mass, most preferably 0.1 to 5 parts by mass.
- the effect of the present invention can be further enhanced by the content ratio of the component (B) to the component (A).
- the aqueous ophthalmic composition of the present invention comprises a sesame oil, castor oil, vitamin A, and chlorobutanol in addition to the components (A) and (B). Contains one or more selected (component (C)).
- component (A), the component (B) and the component (C) exhibits the above-described excellent effects of the present invention.
- Sesame oil refers to a vegetable oil obtained from seeds of a plant belonging to the genus Sesameaceae (Sesamumindicum Linne (Pedaliaceae), etc.).
- the sesame oil used in the present invention is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutical) or physiologically acceptable, and seeds using a known exploitation method and a known purification method are used. What was obtained from this, a commercially available thing, etc. can be used.
- Castor oil refers to vegetable oil obtained from the seeds of plants belonging to the genus Euphorbiaceae (Ricinus communis Linne (Euforbiaceae), etc.).
- the castor oil used in the aqueous ophthalmic composition of the present invention is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Those obtained from seeds using a purification method, commercially available products, and the like can be used.
- Vitamin A is a kind of fat-soluble vitamin and is an essential nutrient for the human body. Vitamin A is a substance having vitamin A activity, and both natural and synthetic products can be used.
- Vitamin A used in the present invention is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutical) or physiologically acceptable, and specifically, retinol, retinal, retinoic acid, these Derivatives, salts and the like.
- vitamin A in the form of derivatives examples include retinol palmitate, retinol acetate, retinol butyrate, retinol propionate, retinol octylate, retinol laurate, retinol oleate, retinol linolenate, retinal, retinoic acid, methyl retinoic acid, retinoin
- examples thereof include ethyl acid, retinoic acid retinol, ⁇ -tocopheryl retinoate, ⁇ -tocopheryl retinoate, ⁇ -tocopheryl retinoate and the like.
- the vitamin A in the salt form is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable, and specifically, an organic acid salt [for example, monocarboxylic acid] Acid salt (acetate, trifluoroacetate, butyrate, palmitate, stearate, etc.), polyvalent carboxylate (fumarate, maleate, succinate, malonate, etc.), oxycarboxyl Acid salt (lactate, tartrate, citrate, etc.), organic sulfonate (methanesulfonate, toluenesulfonate, tosylate, etc.)], inorganic acid salt (eg, hydrochloride, sulfate, Nitrates, hydrobromides, phosphates, etc.) and salts with organic bases (eg methylamine, triethylamine, triethanolamine, morpholine, piperazine, pyrrolidine, tripyridine, picoline, etc.) Salt, etc
- Vitamin A may be either isolated from natural products such as animal materials or chemically synthesized. Vitamin A can also be used as vitamin A oil in the form of vitamin A dissolved in oil. Vitamin A oil may be natural oil extracted and purified from animals, or may be vitamin A dissolved in vegetable oil or the like.
- vitamin A may be used alone or in any combination of two or more.
- vitamins A retinol acetate, retinol palmitate, and vitamin A oil are preferable from the viewpoint of further enhancing the action of shortening the defoaming time.
- Chlorobutanol is a known compound that is also called 1,1,1-trichloro-2-methyl-2-propanol, and may be synthesized by a known method, or may be obtained as a commercial product.
- the content of the component (C) in the aqueous ophthalmic composition of the present invention is not particularly limited, and the type and content of the component (C), the component (A) and the component (B) used together, the aqueous ophthalmology It is appropriately set according to the use, formulation form, method of use and the like of the composition for use.
- the total content of the component (C) is 0.0001 to 5 w / v%, preferably 0.0002 to 1 w / v%, more preferably 0 .0005 to 0.5 w / v%, particularly preferably 0.001 to 0.5 w / v%, more preferably 0.01 to 0.5 w / v%.
- IU is known as an international unit for the amount of vitamin A.
- 1 IU corresponds to about 0.30 ⁇ g retinol
- 1 IU corresponds to about 0.34 ⁇ g retinol acetate
- 1 IU about 0.55 ⁇ g palmitic It is well known to correspond to the acid retinol.
- the content of vitamin A is expressed in IU, for example, based on the total amount of the aqueous ophthalmic composition of the present invention, the content of vitamin A is 200 to 5000000 IU / 100 mL as a total amount, preferably 500 to 1000000 IU / 100 mL. More preferably, it is 1,000 to 500,000 IU / 100 mL, and particularly preferably 2000 to 100,000 IU / 100 mL.
- the content of the component (C) is suitable from the viewpoint of further enhancing the tear oil layer extending action, tear fluid stabilizing action, and preservation effect enhancing action. Moreover, the effect
- the content ratio of the (C) component to the (A) component is not particularly limited, and the types of the (A) component and (C) component, the use of the aqueous ophthalmic composition, and the preparation It is appropriately set according to the form, usage method, and the like.
- the total content of component (A) contained in the aqueous ophthalmic composition of the present invention is 1 part by mass
- the content ratio of component (C) is 0.00002 to 10,000 parts by mass, preferably 0.0001 to 1000 parts by mass, more preferably 0.0002 to 200 parts by mass, still more preferably 0.0005 to 50 parts by mass, particularly preferably 0.001 to 50 parts by mass, and still more preferably 0.01 to 10 parts by mass.
- the effect of the present invention can be further enhanced by the content ratio of the component (C) to the component (A).
- the content ratio of the (C) component to the (B) component is not particularly limited, and the types of the (B) component and (C) component, the use and formulation of the aqueous ophthalmic composition It is appropriately set according to the form, usage method, and the like.
- the content ratio of the component (C) is 0.00002 to 10,000 parts by mass with respect to 1 part by mass of the total content of the component (B) contained in the aqueous ophthalmic composition of the present invention, preferably 0.0001 to 1000 parts by mass, more preferably 0.0002 to 200 parts by mass, still more preferably 0.0005 to 50 parts by mass, particularly preferably 0.001 to 50 parts by mass, and still more preferably 0.005 to 10 parts by mass. Part, more preferably 0.01 to 2 parts by weight.
- the effect of the present invention can be further enhanced by the content ratio of the component (C) to the component (B).
- the aqueous ophthalmic composition of the present invention preferably further contains a buffer agent (component (D)) in addition to the components (A) to (C). Thereby, the effect of the present invention can be further improved.
- a buffer agent component (D)
- the buffer that is preferably contained in the aqueous ophthalmic composition of the present invention is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable.
- buffers include borate buffer, phosphate buffer, carbonate buffer, citrate buffer, acetate buffer, tris buffer, aspartic acid, aspartate, epsilon-aminocaproic acid, etc. It is done.
- These buffering agents may be used alone or in any combination of two or more.
- boric acid buffer boric acid and / or a salt thereof can be used.
- boric acid salt include an alkali metal borate and an alkaline earth metal borate.
- phosphate buffer phosphoric acid and / or a salt thereof can be used.
- the phosphate include an alkali metal phosphate, an alkaline earth metal phosphate, and the like.
- Carbonic acid and / or a salt thereof can be used as the carbonate buffer, and examples of the carbonate include alkali metal carbonates, alkaline earth metal carbonates, and the like.
- Citric acid and / or a salt thereof can be used as the citrate buffer, and examples of the citrate include alkali metal citrate and alkaline earth metal citrate.
- boric acid buffer such as boric acid (orthoboric acid, metaboric acid, tetraboric acid, etc.) or a salt thereof (sodium borate, potassium tetraborate, potassium metaborate, ammonium borate, borax, etc.)
- a phosphoric acid buffer or a salt thereof (disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, trisodium phosphate, dipotassium phosphate, calcium monohydrogen phosphate, diphosphate phosphate; Carbonic acid or a salt thereof (sodium hydrogen carbonate, sodium carbonate, ammonium carbonate, potassium carbonate, calcium carbonate, potassium hydrogen carbonate, magnesium carbonate, etc.); as a citrate buffer, citric acid or its Salt (sodium citrate, potassium citrate, calcium citrate, dihydrate citric acid Sodium acetate, disodium citrate, etc.) Acetic acid or its salts (ammonium acetate, potassium
- the aqueous ophthalmic composition of the present invention contains the buffer of the above component (D), the content thereof includes the type of the buffer, the type and content of other ingredients, the use of the aqueous ophthalmic composition, It is appropriately set according to the formulation form, usage method and the like.
- the total content of component (D) is 0.01 to 10 w / v%, preferably 0.05 to 8 w / v%, more preferably 0. 0.1-5 w / v%, even more preferably 0.2-3 w / v%, particularly preferably 0.5-2.5 w / v%. If it is the said range, the effect of this invention can be show
- the aqueous ophthalmic composition of the present invention further contains a surfactant ((E) component) other than (A) component and (B) component. It is preferable to do. Thereby, the effect of the present invention can be further improved.
- the surfactant (E) is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable, and includes a nonionic surfactant, an amphoteric surfactant, Either an anionic surfactant or a cationic surfactant may be used.
- nonionic surfactant examples include monolauric acid POE (20) sorbitan (polysorbate 20), monopalmitic acid POE (20) sorbitan (polysorbate 40), monostearic acid POE (20) sorbitan (polysorbate 60).
- POE sorbitan fatty acid esters such as POE (20) sorbitan tristearate (polysorbate 65), POE (20) sorbitan (polysorbate 80) monooleate; POE (40) hydrogenated castor oil (polyoxyethylene hydrogenated castor oil 40) POE hydrogenated castor oil such as POE (60) hydrogenated castor oil (polyoxyethylene hydrogenated castor oil 60); POE alkyl ether such as POE (9) lauryl ether; POE- such as POE (20) POP (4) cetyl ether; POP Al Ether; POE (196) POP (67) glycol (Poloxamer 407, Pluronic F127), POE (200) POP (70) Polyoxyethylene-polyoxypropylene block copolymers such as glycol.
- the numbers in parentheses indicate the number of added moles.
- amphoteric surfactant examples include alkyldiaminoethylglycine or a salt thereof (for example, hydrochloride).
- cationic surfactant examples include benzalkonium chloride and benzethonium chloride.
- anionic surfactant examples include alkylbenzene sulfonate, alkyl sulfate, polyoxyethylene alkyl sulfate, aliphatic ⁇ -sulfomethyl ester, ⁇ -olefin sulfonic acid and the like.
- the component (E) surfactant is preferably a nonionic surfactant, more preferably POE sorbitan fatty acid ester, POE hydrogenated castor oil, POE / POP block copolymer, and particularly preferably polysorbate 80. Polyoxyethylene hydrogenated castor oil 60 and poloxamer 407.
- the surfactant of the above component (E) may be used alone or in combination of two or more.
- the content of the surfactant is the type of the surfactant, the type and content of the other compounding components, and the aqueous ophthalmic composition. It is appropriately set according to the use, formulation form, method of use and the like.
- the total content of the component (E) is 0.001 to 3 w / v%, preferably 0.005 to 2 w / v%, more preferably 0. 0.01 to 1 w / v%, particularly preferably 0.05 to 1 w / v%. If it is the said range, the effect of this invention can be show
- the aqueous ophthalmic composition of the present invention is an appropriate amount of various pharmacologically active ingredients and / or physiologically active ingredients, alone or in combination, as long as the effects of the present invention are exhibited. You may contain.
- Such components are not particularly limited, and specific examples of components used in ophthalmic drugs include the following components.
- Antihistamines or antiallergic agents for example, diphenhydramine hydrochloride, chlorpheniramine maleate, etc.
- Decongestant For example, tetrahydrozoline hydrochloride, naphazoline hydrochloride, naphazoline sulfate, epinephrine hydrochloride, ephedrine hydrochloride, methylephedrine hydrochloride, and the like.
- Vitamin For example, flavin adenine dinucleotide sodium, cyanocobalamin, pyridoxine hydrochloride, panthenol, calcium pantothenate, tocopherol acetate, etc.
- Amino acids For example, potassium aspartate, magnesium aspartate, epsilon-aminocaproic acid, sodium chondroitin sulfate and the like.
- Anti-inflammatory agent For example, zinc sulfate, zinc lactate, bromfenac sodium, dipotassium glycyrrhizinate, pranoprofen, allantoin, sodium azulene sulfonate, berberine chloride, berberine sulfate, lysozyme chloride and the like.
- sodium hyaluronate sodium hyaluronate, sulfamethoxazole, sulfamethoxazole sodium, etc.
- Typical additives include the following additives.
- Sugar For example, cyclodextrin and the like.
- Sugar alcohol For example, xylitol, sorbitol, mannitol and the like. These may be d-form, l-form or dl-form.
- Antiseptics, bactericides or antibacterials for example, benzalkonium chloride, benzethonium chloride, polyhexanide hydrochloride, alkyldiaminoethylglycine hydrochloride, sodium benzoate, ethanol, chlorhexidine gluconate, sorbic acid, potassium sorbate, methyl paraoxybenzoate, Ethyl paraoxybenzoate, propyl paraoxybenzoate, butyl paraoxybenzoate, and the like.
- Thickening agent or thickener For example, sodium alginate, methylcellulose, carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, carboxyvinyl polymer, polyvinyl alcohol, polyvinylpyrrolidone, macrogol 4000 and the like.
- Isotonizing agent For example, sodium chloride, potassium chloride and the like.
- Stabilizer For example, dibutylhydroxytoluene, trometamol (trishydroxymethylaminomethane), sodium bisulfite, sodium sulfite and the like.
- Chelating agent for example, ethylenediaminetetraacetic acid disodium (sodium edetate).
- water used in the aqueous ophthalmic composition of the present invention water that is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable may be used, and as such water, specifically, Examples include distilled water, ordinary water, purified water, sterilized purified water, water for injection, distilled water for injection, and the like. These definitions are based on the 16th revised Japanese Pharmacopoeia.
- the pH of the aqueous ophthalmic composition of the present invention is not particularly limited as long as it is within a pharmaceutically, pharmacologically (pharmaceutical) or physiologically acceptable range. Absent.
- An example of the pH of the aqueous ophthalmic composition of the present invention includes a range of 4.0 to 9.5, preferably 5.0 to 9.0, and more preferably 5.5 to 8.5.
- the osmotic pressure of the aqueous ophthalmic composition of the present invention is not particularly limited as long as it is within a range acceptable for a living body.
- the osmotic pressure ratio of the aqueous ophthalmic composition of the present invention 0.5 to 5.0, preferably 0.6 to 3.0, more preferably 0.7 to 2.0, particularly preferably 0.9 to 1.55.
- the adjustment of the osmotic pressure can be performed by a method known in the art using an inorganic salt, a polyhydric alcohol, a sugar alcohol, a sugar or the like.
- the osmotic pressure ratio is the ratio of the osmotic pressure of the sample to 286 mOsm (0.9 w / v% sodium chloride aqueous solution) based on the 16th revised Japanese Pharmacopoeia. Measure with reference to (freezing point depression method).
- sodium chloride Japanese Pharmacopoeia standard reagent
- 0.900 g of the solution is accurately measured and dissolved in purified water to prepare exactly 100 mL, or a commercially available standard solution for osmotic pressure ratio measurement (0.9 w / v% sodium chloride aqueous solution) may be used.
- the viscosity of the aqueous ophthalmic composition of the present invention is not particularly limited as long as it is within a range acceptable for a living body.
- the viscosity at 25 ° C. measured with a rotational viscometer is 0.01 to 1000 mPa ⁇ s, preferably 0.05 to 100 mPa ⁇ s. s, more preferably 0.1 to 10 mPa ⁇ s.
- the dosage form of the aqueous ophthalmic composition in the present invention is not particularly limited as long as it can be used in the ophthalmic field, but is preferably a liquid.
- eye drops also referred to as eye drops or eye drops
- eye drops include artificial tears. Eye drops include eye drops that can be instilled while wearing contact lenses]
- eye wash also referred to as eye wash or eye wash
- eye drops include eye wash that can be washed while wearing contact lenses.
- the aqueous ophthalmic composition of the present invention has a short period of time during which bubbles disappear, and there is little variation in the amount of dripping during use. It is preferably used as an eye drop and contact lens mounting liquid that is easily affected by the above. In addition, since the time for the disappearance of the bubbles is short, it is easy to check foreign matter at the time of manufacture, and it is particularly suitable as an eye drop or eye wash that is a pharmaceutical product in which foreign matter confirmation is essential.
- the aqueous ophthalmic composition of the present invention has an excellent antiseptic action because of its enhanced storage efficacy. For this reason, it is preferably used for a multi-dose type aqueous ophthalmic composition, that is, an aqueous ophthalmic composition that is used several times after the product is once opened, and the aqueous ophthalmic composition is used for several days or It can be stored stably for several weeks or more. Therefore, it is suitably used as an eye drop or eye wash that requires a particularly strict hygiene condition as a pharmaceutical product.
- a container usually used as a container for containing the aqueous ophthalmic composition can be used, and it may be made of glass or plastic.
- the constituent material of the plastic container is not particularly limited.
- polyethylene naphthalate, polyarylate, polyethylene terephthalate, polypropylene, polyethylene, Any one type of polyimide or a mixture of two or more types may be mentioned.
- a copolymer containing other polyester units and imide units mainly composed of any one of ethylene-2,6-naphthalate units, arylate units, ethylene terephthalate units, propylene units, ethylene units and imide units can be mentioned.
- the polyethylene terephthalate means what is 50 w / w% or more with respect to the weight of the whole constituent material of a container.
- the structure, constituent materials and the like of the peripheral portion of the container inlet such as a nozzle provided in the container for storing the aqueous ophthalmic composition of the present invention are not particularly limited.
- the structure of the container spout peripheral part such as a nozzle it may be a structure generally adopted as a spout (for example, a nozzle) of a container for an ophthalmic composition (for example, an eye drop container), and is integrated with the container body. It may be molded and may be molded separately from the container body.
- the constituent material of the peripheral part of the spout or the spout (for example, nozzle) for example, the same material as that of the plastic container is exemplified.
- a spout containing polyethylene or polypropylene as a constituent material is suitable.
- the type of polyethylene include high-density polyethylene and low-density polyethylene.
- spouts containing low-density polyethylene as a constituent material are suitable.
- the nozzle used for an eye drop container is suitable.
- a preferable combination of the container for containing the aqueous ophthalmic composition of the present invention and the peripheral part of the container mouth is a combination of a polyethylene terephthalate container and a peripheral part of the polyethylene container mouth, more preferably a polyethylene terephthalate eye drop container and a polyethylene
- the aqueous ophthalmic composition of the present invention shortens the defoaming time of the foam, suppresses variation in the amount of dripping during use, and can be instilled in a certain amount for each use. It is suitable as an eye drop containing a physiologically active ingredient. Uses of such eye drops include eye drops for dry eye, eye drops for removing hyperemia, eye drops for antibacterial use, eye drops for anti-inflammation, eye drops for suppressing itching, eye drops for suppressing fatigue, eye dryness An eye drop etc. are mentioned.
- the present invention is particularly useful as an eye drop for dry eye or an eye drop for suppressing dryness of the eye, because it is excellent in tear stabilization and tear oil layer extension.
- the present invention provides (A) polyoxyethylene castor oil, (B) polyethylene glycol monostearate, and (C) sesame oil, castor oil, vitamin A for the production of an aqueous ophthalmic composition. And at least one use selected from the group consisting of chlorobutanol.
- the present invention provides, from another viewpoint, (A) polyoxyethylene castor oil, (B) polyethylene glycol monostearate, and (C) sesame oil, castor oil, vitamin A, and chloro as an aqueous ophthalmic composition.
- A polyoxyethylene castor oil
- B polyethylene glycol monostearate
- C sesame oil, castor oil, vitamin A, and chloro as an aqueous ophthalmic composition.
- a composition comprising at least one selected from the group consisting of butanol.
- the present invention is (A) polyoxyethylene castor oil, (B) polyethylene glycol monostearate, and (C) sesame oil, castor oil, vitamins for use as an aqueous ophthalmic composition.
- a composition comprising at least one selected from the group consisting of A and chlorobutanol is provided.
- Foaming suppression method As described above, in the aqueous ophthalmic composition of the present invention, foaming in the aqueous ophthalmic composition can be suppressed by adding the component (A), the component (B), and the component (C), and as a result. In addition, since the dissolution confirmation and foreign matter inspection processes are completed in a short time, the production efficiency is greatly improved.
- the present invention is selected from the group consisting of (A) polyoxyethylene castor oil, (B) polyethylene glycol monostearate, and (C) sesame oil, castor oil, vitamin A, and chlorobutanol.
- A polyoxyethylene castor oil
- B polyethylene glycol monostearate
- C sesame oil, castor oil, vitamin A, and chlorobutanol.
- the present invention relates to an aqueous ophthalmic composition containing (A) polyoxyethylene castor oil and (B) polyethylene glycol monostearate, from the group consisting of (C) sesame oil, castor oil, vitamin A, and chlorobutanol.
- A polyoxyethylene castor oil
- B polyethylene glycol monostearate
- component (A), the component (B), and the component (C) coexist, they may be added simultaneously or separately, and the order thereof is not particularly limited.
- aqueous ophthalmic composition is an eye drop and a contact lens mounting solution.
- the foam defoaming time can be shortened in the aqueous ophthalmic composition by containing the component (A), the component (B) and the component (C). As a result, variation in the amount of dripping during use can be suppressed.
- the present invention is further selected from the group consisting of (A) polyoxyethylene castor oil, (B) polyethylene glycol monostearate, and (C) sesame oil, castor oil, vitamin A, and chlorobutanol from another viewpoint.
- water-based ophthalmic composition is provided by making the aqueous
- the present invention relates to an aqueous ophthalmic composition containing (A) polyoxyethylene castor oil and (B) polyethylene glycol monostearate, from the group consisting of (C) sesame oil, castor oil, vitamin A, and chlorobutanol.
- A polyoxyethylene castor oil
- B polyethylene glycol monostearate
- the present invention also includes at least one selected from the group consisting of (A) polyoxyethylene castor oil, (B) polyethylene glycol monostearate, and (C) sesame oil, castor oil, vitamin A, and chlorobutanol.
- A polyoxyethylene castor oil
- B polyethylene glycol monostearate
- C sesame oil
- castor oil vitamin A
- chlorobutanol sesame oil
- aqueous ophthalmic composition is a method for suppressing variations in the amount of dripping during use in the aqueous ophthalmic composition.
- the present invention relates to an aqueous ophthalmic composition containing (A) polyoxyethylene castor oil and (B) polyethylene glycol monostearate, from the group consisting of (C) sesame oil, castor oil, vitamin A, and chlorobutanol.
- A polyoxyethylene castor oil
- B polyethylene glycol monostearate
- component (A), the component (B), and the component (C) coexist, they may be added simultaneously or separately, and the order thereof is not particularly limited.
- aqueous ophthalmic composition is an eye drop and a contact lens mounting solution.
- the storage efficacy can be enhanced in the aqueous ophthalmic composition by containing the component (A), the component (B) and the component (C).
- the present invention is further selected from the group consisting of (A) polyoxyethylene castor oil, (B) polyethylene glycol monostearate, and (C) sesame oil, castor oil, vitamin A, and chlorobutanol from another viewpoint.
- these methods are preferably used for multi-dose type aqueous ophthalmic compositions, that is, aqueous ophthalmic compositions that are used several times after the product is once opened.
- aqueous ophthalmic compositions include a multi-dose type eye drop, a multi-dose type eye wash, a multi-dose type contact lens mounting solution, and a multi-dose type contact lens care product.
- the lacrimal fluid can be stabilized by containing the component (A), the component (B), and the component (C), and as a result, Dry eye or dry eyes can be suppressed.
- the present invention is further selected from the group consisting of (A) polyoxyethylene castor oil, (B) polyethylene glycol monostearate, and (C) sesame oil, castor oil, vitamin A, and chlorobutanol from another viewpoint.
- the present invention also includes at least one selected from the group consisting of (A) polyoxyethylene castor oil, (B) polyethylene glycol monostearate, and (C) sesame oil, castor oil, vitamin A, and chlorobutanol.
- A polyoxyethylene castor oil
- B polyethylene glycol monostearate
- C sesame oil, castor oil, vitamin A, and chlorobutanol.
- the aqueous ophthalmic composition obtained by the method is suitable for dry eye or for suppressing dry eyes.
- component (A), the component (B), and the component (C) coexist, they may be added simultaneously or separately, and the order thereof is not particularly limited.
- aqueous ophthalmic composition is an eye drop and a contact lens mounting solution.
- the lacrimal oil layer is easily spread in a short time after blinking by containing the components (A), (B) and (C), that is, Since the tear oil layer stretching action is high, dry eye or dry eyes can be suppressed.
- the present invention is further selected from the group consisting of (A) polyoxyethylene castor oil, (B) polyethylene glycol monostearate, and (C) sesame oil, castor oil, vitamin A, and chlorobutanol from another viewpoint.
- a method of imparting a tear oil layer stretching action to the aqueous ophthalmic composition by including at least one of the above in the aqueous ophthalmic composition is provided.
- the aqueous ophthalmic composition obtained by the method is suitable for dry eye or for suppressing dry eyes.
- component (A), the component (B), and the component (C) coexist, they may be added simultaneously or separately, and the order thereof is not particularly limited.
- aqueous ophthalmic composition is an eye drop and a contact lens mounting solution.
- an odor can be suppressed in an aqueous ophthalmic composition by containing (A) component, (B) component, and (C) component.
- the present invention is further selected from the group consisting of (A) polyoxyethylene castor oil, (B) polyethylene glycol monostearate, and (C) sesame oil, castor oil, vitamin A, and chlorobutanol from another viewpoint.
- a method for suppressing odor in the aqueous ophthalmic composition is provided by including at least one of them in the aqueous ophthalmic composition.
- the present invention relates to an aqueous ophthalmic composition containing (A) polyoxyethylene castor oil and (B) polyethylene glycol monostearate, from the group consisting of (C) sesame oil, castor oil, vitamin A, and chlorobutanol.
- A polyoxyethylene castor oil
- B polyethylene glycol monostearate
- aqueous ophthalmic composition is an eye drop and a contact lens mounting solution.
- polyoxyethylene castor oil 35 having an average added mole number of ethylene oxide that conforms to the standard of polyoxyethylene castor oil of pharmaceutical additive standard 2003 is 35
- the polyoxyethylene castor oil 10 is one having an average added mole number of ethylene oxide that conforms to the standard of the polyoxyethylene castor oil of the pharmaceutical additive standard 2003
- the polyoxyl 40 stearate is the standard of pharmaceutical additive.
- the average added mole number of ethylene oxide that conforms to the standard of 2003 polyoxyl stearate is 40, and polysorbate 80 and polyoxyethylene hydrogenated castor oil 60 (HCO 60) that conform to the Japanese Pharmacopoeia are used. .
- Test Example 1 Foaming suppression test
- Table 1 The aqueous ophthalmic composition shown in Table 1 below was prepared according to a conventional method and used as a test solution.
- Foaming rate (%) (initial foaming (height) of each test solution) / (initial foaming (height) of corresponding comparative example) ⁇ 100
- the corresponding comparative examples are specifically Comparative Example 1 for Examples 1, 3 and 4, and Comparative Example 2 for Examples 2 and 5.
- each of the aqueous ophthalmic compositions of Examples 6 to 13 and Comparative Examples 3 to 6 was filled into 50 mL glass centrifuge tubes, and these were 1500 using RECIPAD SHAKER SR-2w (TAITEC). I swung around. Immediately after the end of shaking, visually measure the height of the foam part and confirm that the foam is decreasing over time, while measuring the height of the foam part half the time immediately after the end of shaking. It was measured as the foam half time (min). The value of the bubble half-life (min) of each corresponding comparative example was 100%, and the defoaming time ratio (%) until the bubble half of each test solution was calculated according to the following formula.
- Defoaming time ratio (%) (foam half time (minutes) of each test solution) / (foam half time (minutes) of corresponding comparative example) ⁇ 100
- Test Example 3 Odor measurement test
- Table 3-1 and Table 3-2 Aqueous ophthalmic compositions having the compositions shown in Table 3-1 and Table 3-2 below were prepared by a conventional method and used as test solutions.
- the aqueous ophthalmic compositions of Examples 14 to 17 and Comparative Examples 7 to 9 were filled in 15 ml each of a 15 ml capacity polyethylene terephthalate eye drop container, and a polyethylene nozzle was attached.
- the books were stored at 4 ° C. for 1 month and the remaining 5 books were stored at 60 ° C. for 2 weeks.
- One drop of each aqueous ophthalmic composition after storage was dropped on the arm, spread to a 10-yen coin size, smelled, and evaluated by the VAS method.
- Test Example 4 Preservative efficacy test
- Table 4 The aqueous ophthalmic composition shown in Table 4 below was prepared according to a conventional method. Then, the preservation efficacy test of the aqueous ophthalmic compositions of Example 18 and Comparative Examples 10 to 13 was performed by the following method.
- Staphylococcus aureus (ATCC 6538) was inoculated on the surface of a soy bean casein digest slope medium and cultured at 33 ° C. for 24 hours.
- the cultured cells were aseptically collected with a platinum loop and suspended in an appropriate amount of sterile physiological saline to prepare a bacterial suspension containing about 1 ⁇ 10 6 CFU / mL viable bacteria.
- the number of viable bacteria in the suspension was measured by separately culturing.
- 5 mL of the aqueous ophthalmic composition of Example 18 and Comparative Examples 10 to 13 was filled in a 15 mL CORNING conical tube (PET).
- aqueous ophthalmic compositions were inoculated with Staphylococcus aureus bacterial solution (suspended in physiological saline) so that the viable count (final concentration) was about 10 4 CFU / mL, and stirred well to prepare a sample. .
- Samples were stored for 96 hours at 23 ° C., protected from light. After 96 hours, a sample containing the bacteria was prepared to an appropriate concentration for counting, seeded on lecithin, polysorbate 80, soy bean, casein, digest, agar medium (SCDLP agar medium) and cultured at 33 ° C overnight. The number of viable bacteria was determined by counting the number of colonies observed. The results are also shown in Table 4.
- Example 10 As shown in Table 4, in the test solution containing either one of polyoxyethylene castor oil or polyoxyl stearate together with the phosphate buffer (Comparative Examples 11 and 12), the test solution containing only the phosphate buffer (Comparative Example) Compared with 10), the preservative effect was almost the same or attenuated. Further, even in a test solution (Comparative Example 13) containing polyoxyethylene castor oil and retinol palmitate together with a phosphate buffer, the storage efficacy is reduced compared to a test solution containing only a phosphate buffer (Comparative Example 10). did. On the other hand, it was completely unexpected that in Example 18 containing a combination of three components of polyoxyethylene castor oil, polyoxyl stearate and retinol palmitate, the effect of enhancing the storage efficacy was remarkably recognized.
- Sudan Black manufactured by Wako Pure Chemical Industries, Ltd.
- Wako Pure Chemical Industries, Ltd. is a colorant for facilitating observation of oil extension.
- Oil reservoir extension score The oil layer extends evenly over the whole ... Some unevenness is observed in the oil layer in the center, or some oil layer is adsorbed on the wall surface. The oil layer in the center is non-uniform, and the oil layer is slightly adsorbed on the wall surface. Oil layer is uneven overall.
- each of the aqueous ophthalmic compositions of Example 22 and Comparative Example 20 was filled into 15 mL polyethylene terephthalate eye drop containers, and a polyethylene nozzle was attached.
- a tear fluid observation device DR-1 manufactured by Kowa Co., Ltd.
- the feeling of irritation immediately after instillation and the feeling of dryness when waking up the next morning were evaluated by the VAS method. That is, regarding the feeling of irritation, at both ends of a straight line of 10 cm, “not feeling irritation” is 0 cm, “maximum irritation that has been felt so far” is 10 cm, and it is felt by instillation of each aqueous ophthalmic composition. One point on the straight line corresponding to the feeling of irritation was shown to the subject, and the distance from the 0 cm point was measured to obtain the point of irritation. Similarly, the next morning's dry feeling was 0 cm for “not feeling dry” at both ends of a straight line of 10 cm, and 10 cm for “maximum dry feeling that had been felt so far”. The dry feeling score was evaluated. The results are also shown in Table 6.
- Example 22 As shown in Table 6, in Comparative Example 20, a slight break occurred immediately after instillation, but surprisingly, in Example 22, no break occurred even after 60 minutes of eye opening after 5 minutes of instillation. The dry feeling was not felt after waking up the next morning. Furthermore, although the stimulus was very felt in Comparative Example 20, the stimulus was not felt in Example 22.
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Abstract
Description
項1-1.(A)ポリオキシエチレンヒマシ油、(B)モノステアリン酸ポリエチレングリコール、並びに(C)ゴマ油、ヒマシ油、ビタミンA及びクロロブタノールからなる群より選択される少なくとも一種を含有する、水性眼科組成物。
項1-2.(A)成分が、酸化エチレンの平均付加モル数が2~70モルのポリオキシエチレンヒマシ油である、項1-1に記載の水性眼科組成物。
項1-3.(B)成分が、酸化エチレンの平均付加モル数が2~150モルのモノステアリン酸ポリエチレングリコールである、項1-1又は項1-2に記載の水性眼科組成物。
項1-4.水性眼科組成物の総量を基準として、(A)成分の含有量が、総量で0.0001~5w/v%である、項1-1乃至1-3のいずれかに記載の水性眼科組成物。
項1-5.水性眼科組成物の総量を基準として、(B)成分の含有量が、総量で0.0001~5w/v%である、項1-1乃至1-4のいずれかに記載の水性眼科組成物。
項1-6.(A)成分の総含有量1質量部に対する(B)成分の含有比率が、総含有量で0.001~100質量部である、項1-1乃至1-5のいずれかに記載の水性眼科組成物。
項1-7.水性眼科組成物の総量を基準として、(C)成分の含有量が、総量で0.0001~5w/v%である、項1-1乃至1-6のいずれかに記載の水性眼科組成物。
項1-8.(A)成分の総含有量1質量部に対する(C)成分の含有比率が、総含有量で0.00002~10000質量部である、項1-1乃至1-7のいずれかに記載の水性眼科組成物。
項1-9.(B)成分の総含有量1質量部に対する(C)成分の含有比率が、総含有量で0.00002~10000質量部である、項1-1乃至1-8のいずれかに記載の水性眼科組成物。
項1-10.さらに、(D)緩衝剤を含有する、項1-1乃至1-9のいずれかに記載の水性眼科組成物。
項1-11.水性眼科組成物の総量を基準として、(D)成分の含有量が、総量で0.01~20w/v%である、項1-10に記載の水性眼科組成物。
項1-12.さらに、(E)成分として、(A)成分及び(B)成分以外の界面活性剤を含有する、項1-1乃至1-11のいずれかに記載の水性眼科組成物。
項1-13.(E)成分が、ポリオキシエチレンソルビタン脂肪酸エステル、ポリオキシエチレン硬化ヒマシ油、及びポリオキシエチレン・ポリオキシプロピレン・ブロックコポリマーからなる群より選択される少なくとも一種である、項1-12に記載の水性眼科組成物。
項1-14.水性眼科組成物の総量を基準として、(E)成分の含有量が、総量で0.0001~5w/v%である、項1-12又は1-13に記載の水性眼科組成物。
項1-15.点眼剤である項1-1乃至1-14のいずれかに記載の水性眼科組成物。
項1-16.洗眼剤である項1-1乃至1-14のいずれかに記載の水性眼科組成物。
項1-17.コンタクトレンズ装着液である項1-1乃至1-14のいずれかに記載の水性眼科組成物。
項1-18.コンタクトレンズケア用剤である項1-1乃至1-14のいずれかに記載の水性眼科組成物。
項1-19.ドライアイ用又は目の乾きの抑制用である、項1-1乃至1-18のいずれかに記載の水性眼科組成物。
項2-1.(A)ポリオキシエチレンヒマシ油、(B)モノステアリン酸ポリエチレングリコール、並びに(C)ゴマ油、ヒマシ油、ビタミンA及びクロロブタノールからなる群より選択される少なくとも一種を、水性眼科組成物に含有させることにより、該水性眼科組成物における泡立ちを抑制する方法。
項2-2.(A)ポリオキシエチレンヒマシ油及び(B)モノステアリン酸ポリエチレングリコールを含有する水性眼科組成物に、(C)ゴマ油、ヒマシ油、ビタミンA及びクロロブタノールからなる群より選択される少なくとも一種を含有させることにより、該水性眼科組成物における泡立ちを抑制する方法。
項3-1.(A)ポリオキシエチレンヒマシ油、(B)モノステアリン酸ポリエチレングリコール、並びに(C)ゴマ油、ヒマシ油、ビタミンA及びクロロブタノールからなる群より選択される少なくとも一種を、水性眼科組成物に含有させることにより、該水性眼科組成物における消泡時間を短縮させる方法。
項3-2.(A)ポリオキシエチレンヒマシ油及び(B)モノステアリン酸ポリエチレングリコールを含有する水性眼科組成物に、(C)ゴマ油、ヒマシ油、ビタミンA及びクロロブタノールからなる群より選択される少なくとも一種を含有させることにより、該水性眼科組成物における消泡時間を短縮させる方法。
項3-3.(A)ポリオキシエチレンヒマシ油、(B)モノステアリン酸ポリエチレングリコール、並びに(C)ゴマ油、ヒマシ油、ビタミンA及びクロロブタノールからなる群より選択される少なくとも一種を、水性眼科組成物に含有させることにより、該水性眼科組成物における使用時の滴下量のバラツキを抑制する方法。
項3-4.(A)ポリオキシエチレンヒマシ油及び(B)モノステアリン酸ポリエチレングリコールを含有する水性眼科組成物に、(C)ゴマ油、ヒマシ油、ビタミンA及びクロロブタノールからなる群より選択される少なくとも一種を含有させることにより、該水性眼科組成物における使用時の滴下量のバラツキを抑制する方法。
項4.(A)ポリオキシエチレンヒマシ油、(B)モノステアリン酸ポリエチレングリコール、並びに(C)ゴマ油、ヒマシ油、ビタミンA及びクロロブタノールからなる群より選択される少なくとも一種を、水性眼科組成物に含有させることにより、該水性眼科組成物における保存効力を増強する方法。
項5-1.(A)ポリオキシエチレンヒマシ油、(B)モノステアリン酸ポリエチレングリコール、並びに(C)ゴマ油、ヒマシ油、ビタミンA及びクロロブタノールからなる群より選択される少なくとも一種を水性眼科組成物に含有させることにより、該水性眼科組成物に涙液安定化作用を付与する方法。
項5-2.(A)ポリオキシエチレンヒマシ油、(B)モノステアリン酸ポリエチレングリコール、並びに(C)ゴマ油、ヒマシ油、ビタミンA及びクロロブタノールからなる群より選択される少なくとも一種を水性眼科組成物に含有させることにより、該水性眼科組成物に涙液油層伸展作用を付与する方法。
項6-1.(A)ポリオキシエチレンヒマシ油、(B)モノステアリン酸ポリエチレングリコール、並びに(C)ゴマ油、ヒマシ油、ビタミンA及びクロロブタノールからなる群より選択される少なくとも一種を水性眼科組成物に含有させることにより、該水性眼科組成物ににおける臭気を抑制する方法。
項6-2.(A)ポリオキシエチレンヒマシ油及び(B)モノステアリン酸ポリエチレングリコールを含有する水性眼科組成物に、(C)ゴマ油、ヒマシ油、ビタミンA、及びクロロブタノールからなる群より選択される少なくとも一種を含有させることにより、該水性眼科組成物における臭気を抑制する方法。
項7-1.水性眼科組成物の製造のための、(A)ポリオキシエチレンヒマシ油、(B)モノステアリン酸ポリエチレングリコール、並びに(C)ゴマ油、ヒマシ油、ビタミンA及びクロロブタノールからなる群より選択される少なくとも一種の使用。
項7-2.水性眼科組成物が、上記項1-1乃至1-18のいずれかに記載の組成物である、項7-1に記載の使用。
項8-1.水性眼科組成物としての、(A)ポリオキシエチレンヒマシ油、(B)モノステアリン酸ポリエチレングリコール、並びに(C)ゴマ油、ヒマシ油、ビタミンA及びクロロブタノールからなる群より選択される少なくとも一種を含む組成物の使用。
項8-2.組成物が、上記項1-1乃至1-18のいずれかに記載の組成物である、項8-1に記載の使用。
項9-1.水性眼科組成物としての使用のための、(A)ポリオキシエチレンヒマシ油、(B)モノステアリン酸ポリエチレングリコール、並びに(C)ゴマ油、ヒマシ油、ビタミンA及びクロロブタノールからなる群より選択される少なくとも一種を含む組成物。
項9-2.上記項1-1乃至1-18のいずれかに記載されたものである、項9-1に記載の組成物。
項10-1.水と、(A)ポリオキシエチレンヒマシ油と、(B)モノステアリン酸ポリエチレングリコールと、(C)ゴマ油、ヒマシ油、ビタミンA及びクロロブタノールからなる群より選択される少なくとも一種とを混合する工程を含む、水性眼科組成物の製造方法。
項10-2.水性眼科組成物が、上記項1-1乃至1-18のいずれかに記載の組成物である、項10-1に記載の製造方法。
本発明の水性眼科組成物は、(A)ポリオキシエチレンヒマシ油、(B)モノステアリン酸ポリエチレングリコール、並びに(C)ゴマ油、ヒマシ油、ビタミンA及びクロロブタノールからなる群より選択される少なくとも一種を含有する。
(1)ポリオキシエチレンヒマシ油
本発明の水性眼科組成物は、ポリオキシエチレンヒマシ油((A)成分)を含有する。これを後述する(B)モノステアリン酸ポリエチレングリコール、並びに(C)ゴマ油、ヒマシ油、ビタミンA及びクロロブタノールからなる群より選択される少なくとも一種と併用することによって、上記した本発明の優れた効果が発揮される。
本発明の水性眼科組成物は、上記(A)成分に加えて、モノステアリン酸ポリエチレングリコール((B)成分)を含有する。これらと、さらに後述する(C)ゴマ油、ヒマシ油、ビタミンA及びクロロブタノールからなる群より選択される少なくとも一種とを併用することによって、上記した本発明の優れた効果が発揮される。
本発明の水性眼科組成物は、上記(A)成分及び(B)成分に加えて、ゴマ油、ヒマシ油、ビタミンA及びクロロブタノールからなる群から選択される1種以上((C)成分)を含有する。このように、(A)成分、(B)成分及び(C)成分を併用することによって、上記した本発明の優れた効果が発揮される。
本発明の水性眼科組成物は、(A)~(C)成分の他に、さらに、緩衝剤((D)成分)を含有することが好ましい。これにより、本発明の効果をより一層向上させることができる。
本発明の水性眼科組成物は、さらに、(A)成分及び(B)成分以外の界面活性剤((E)成分)を含有することが好ましい。これにより、本発明の効果をより一層向上させることができる。
本発明の水性眼科組成物は、本発明の効果が奏される限り、上記成分の他に、種々の薬理活性成分及び/又は生理活性成分を単独又は適宜組み合わせて適当量含有してもよい。このような成分は特に制限されず、具体的には、眼科用薬において用いられる成分としては、次のような成分が挙げられる。
本発明の水性眼科組成物のpHについては、医薬上、薬理学的に(製薬上)又は生理学的に許容される範囲内であれば特に限定されるものではない。本発明の水性眼科組成物のpHの一例として、4.0~9.5、好ましくは5.0~9.0、さらに好ましくは5.5~8.5となる範囲が挙げられる。
本発明における水性眼科組成物の剤型については、眼科分野で使用可能である限り特に制限されないが、液状が好ましい。本発明の水性眼科組成物の具体例として、点眼剤(点眼液又は点眼薬ともいう)[但し、点眼剤には人工涙液を含む。また点眼剤には、コンタクトレンズ装用中に点眼可能な点眼剤を含む]、洗眼剤(洗眼液又は洗眼薬ともいう)[但し、洗眼剤にはコンタクトレンズ装用中に洗眼可能な洗眼剤を含む]、コンタクトレンズ装着液、コンタクトレンズケア用品(コンタクトレンズ消毒剤、コンタクトレンズ用保存剤、コンタクトレンズ用洗浄剤、コンタクトレンズ用洗浄保存剤、コンタクトレンズ用消毒・保存・洗浄剤(コンタクトレンズ用マルチパーパスソリューション))等が挙げられる。本発明の水性眼科組成物は、泡の消える時間が短く、使用時の滴下量のバラツキが少ないため、他の剤型と比較して特に一回の使用量が少なく、泡による滴下量のバラツキの影響を受けやすい、点眼剤及びコンタクトレンズ装着液として、好適に用いられる。また、泡の消える時間が短いため、製造時の異物確認が行いやすく、特に異物確認が必須とされる医薬品である点眼剤又は洗眼剤として好適である。
前述したように、本発明の水性眼科組成物では、(A)成分、(B)成分及び(C)成分を含有させることによって、水性眼科組成物における泡立ちを抑制することができ、さらにその結果、溶解確認及び異物検査工程等が短時間ですむため、製造効率が大幅に改善される。
前述したように、本発明の水性眼科組成物では、(A)成分、(B)成分及び(C)成分を含有させることによって、水性眼科組成物において泡の消泡時間を短縮させることができ、さらにその結果、使用時の滴下量のバラツキを抑制することができる。
また、前述したように、本発明の水性眼科組成物では、(A)成分、(B)成分及び(C)成分を含有させることによって、水性眼科組成物において保存効力を増強させることができる。
また、前述したように、本発明の水性眼科組成物では、(A)成分、(B)成分及び(C)成分を含有させることによって、涙液を安定化させることができ、さらにその結果、ドライアイ又は目の乾きを抑制することができる。
また、前述したように、本発明の水性眼科組成物では、(A)成分、(B)成分及び(C)成分を含有させることによって、涙液油層が瞬目後に短時間で広がりやすく、すなわち涙液油層伸展作用が高いため、ドライアイ又は目の乾きを抑制することができる。
また、前述したように、本発明の水性眼科組成物では、(A)成分、(B)成分及び(C)成分を含有させることによって、水性眼科組成物において臭気を抑制することができる。
下記表1に示す水性眼科組成物を、常法に従い調製し、試験液とした。以下の方法で、実施例1~5、比較例1及び2の水性眼科組成物の泡立ち抑制効果について評価した。
下記表2-1及び2-2に示す水性眼科組成物を、常法に従い調製し、試験液とした。そして、以下の方法で、実施例6~13、比較例3~6の水性眼科組成物の消泡促進効果について評価した。
下記表3-1及び表3-2に示す組成の水性眼科組成物を、常法により調製し、試験液とした。以下の方法で、実施例14~17及び比較例7~9の水性眼科組成物の臭気測定試験を実施した。
下記表4に示す水性眼科組成物を、常法に従い調製した。そして、以下の方法で、実施例18及び比較例10~13の水性眼科組成物の保存効力試験を実施した。
下記表5-1及び表5-2に示す水性眼科組成物を、常法に従い調製した。以下の方法で、実施例19~21、比較例14~19の水性眼科組成物の油層伸展試験を実施した。
油層が全体に均一に伸展している・・・・・・・・・・・・・・・・・・・◎
中央部の油層に若干不均一さがみられるか、壁面部に若干油層が吸着している・・○
中央部の油層が不均一であり、壁面部に若干油層が吸着している・・・・・△
油層が全体的に不均一である・・・・・・・・・・・・・・・・・・・・・×
下記表6に示す組成の水性眼科組成物を、常法により調製した。そして、以下の方法で、実施例22及び比較例20の水性眼科組成物の涙液安定化試験を実施した。
ブレイク無 ・・・・・・・・・・ -
軽度のブレイク有 ・・・・・・・ +
中等度のブレイク有 ・・・・・・ ++
重度のブレイク有 ・・・・・・・ +++
目が乾いて開眼を継続できず ・・ ++++
Claims (7)
- (A)ポリオキシエチレンヒマシ油、(B)モノステアリン酸ポリエチレングリコール、並びに(C)ゴマ油、ヒマシ油、ビタミンA及びクロロブタノールからなる群より選択される少なくとも一種を含有する、水性眼科組成物。
- さらに、(D)緩衝剤を含有する、請求項1に記載の水性眼科組成物。
- さらに、(E)(A)成分及び(B)成分以外の界面活性剤を含有する、請求項1又は2に記載の水性眼科組成物。
- 点眼剤、洗眼剤、コンタクトレンズ装着液又はコンタクトレンズケア用剤である、請求項1~3のいずれか一項に記載の水性眼科組成物。
- ドライアイ用又は目の乾きの抑制用である、請求項1~4のいずれか一項に記載の水性眼科組成物。
- (A)ポリオキシエチレンヒマシ油、(B)モノステアリン酸ポリエチレングリコール、並びに(C)ゴマ油、ヒマシ油、ビタミンA及びクロロブタノールからなる群より選択される少なくとも一種を水性眼科組成物に含有させることにより、該水性眼科組成物における消泡時間を短縮させる方法。
- (A)ポリオキシエチレンヒマシ油、(B)モノステアリン酸ポリエチレングリコール、並びに(C)ゴマ油、ヒマシ油、ビタミンA及びクロロブタノールからなる群より選択される少なくとも一種を水性眼科組成物に含有させることにより、該水性眼科組成物に涙液安定化作用を付与する方法。
Priority Applications (5)
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JP2014551072A JP5873573B2 (ja) | 2012-12-04 | 2013-11-29 | 水性眼科組成物 |
CN201380059536.4A CN104797241B (zh) | 2012-12-04 | 2013-11-29 | 水性眼科组合物 |
US14/384,810 US9427473B2 (en) | 2012-12-04 | 2013-11-29 | Aqueous ophthalmic composition |
HK15108564.2A HK1207964A1 (en) | 2012-12-04 | 2015-09-02 | Aqueous ophthalmic composition |
US15/147,415 US20160243030A1 (en) | 2012-12-04 | 2016-05-05 | Aqueous Ophthalmic Composition |
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JP2012265841 | 2012-12-04 | ||
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US14/384,810 A-371-Of-International US9427473B2 (en) | 2012-12-04 | 2013-11-29 | Aqueous ophthalmic composition |
US15/147,415 Continuation US20160243030A1 (en) | 2012-12-04 | 2016-05-05 | Aqueous Ophthalmic Composition |
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WO2014087931A1 true WO2014087931A1 (ja) | 2014-06-12 |
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US (2) | US9427473B2 (ja) |
JP (1) | JP5873573B2 (ja) |
CN (2) | CN107260660A (ja) |
HK (1) | HK1207964A1 (ja) |
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Cited By (1)
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JP2019214560A (ja) * | 2018-06-08 | 2019-12-19 | ロート製薬株式会社 | 洗眼剤組成物 |
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US11260035B2 (en) | 2016-10-12 | 2022-03-01 | Ps Therapies Ltd | Topical compositions and methods of use thereof |
US11583496B2 (en) | 2016-10-12 | 2023-02-21 | PS Therapy Inc. | Drug vehicle compositions and methods of use thereof |
KR102453524B1 (ko) * | 2016-12-19 | 2022-10-12 | 라이온 가부시키가이샤 | 안과용 조성물 및 그 제조 방법 |
AT521983A1 (de) * | 2018-11-26 | 2020-06-15 | Orphanix Gmbh | Wässrige pädiatrische Retinolpräparate |
TW202304456A (zh) * | 2021-07-16 | 2023-02-01 | 晶碩光學股份有限公司 | 用於眼科產品之液態組成物 |
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2013
- 2013-11-29 WO PCT/JP2013/082188 patent/WO2014087931A1/ja active Application Filing
- 2013-11-29 US US14/384,810 patent/US9427473B2/en active Active
- 2013-11-29 CN CN201710407567.4A patent/CN107260660A/zh active Pending
- 2013-11-29 CN CN201380059536.4A patent/CN104797241B/zh active Active
- 2013-11-29 JP JP2014551072A patent/JP5873573B2/ja active Active
- 2013-12-03 TW TW102144155A patent/TWI586368B/zh active
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2015
- 2015-09-02 HK HK15108564.2A patent/HK1207964A1/xx unknown
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HK1207964A1 (en) | 2016-02-19 |
TW201427691A (zh) | 2014-07-16 |
CN104797241A (zh) | 2015-07-22 |
JPWO2014087931A1 (ja) | 2017-01-05 |
TWI586368B (zh) | 2017-06-11 |
CN107260660A (zh) | 2017-10-20 |
US20150018416A1 (en) | 2015-01-15 |
US20160243030A1 (en) | 2016-08-25 |
US9427473B2 (en) | 2016-08-30 |
JP5873573B2 (ja) | 2016-03-01 |
CN104797241B (zh) | 2018-03-27 |
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