WO2018117014A1 - Composition ophtalmique et son procédé de fabrication - Google Patents

Composition ophtalmique et son procédé de fabrication Download PDF

Info

Publication number
WO2018117014A1
WO2018117014A1 PCT/JP2017/045278 JP2017045278W WO2018117014A1 WO 2018117014 A1 WO2018117014 A1 WO 2018117014A1 JP 2017045278 W JP2017045278 W JP 2017045278W WO 2018117014 A1 WO2018117014 A1 WO 2018117014A1
Authority
WO
WIPO (PCT)
Prior art keywords
composition
component
castor oil
oil
ophthalmic composition
Prior art date
Application number
PCT/JP2017/045278
Other languages
English (en)
Japanese (ja)
Inventor
雅貴 吉田
裕美 高村
Original Assignee
ライオン株式会社
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by ライオン株式会社 filed Critical ライオン株式会社
Priority to KR1020197006629A priority Critical patent/KR102453524B1/ko
Priority to JP2018557757A priority patent/JPWO2018117014A1/ja
Publication of WO2018117014A1 publication Critical patent/WO2018117014A1/fr

Links

Classifications

    • 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
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A61K31/355—Tocopherols, e.g. vitamin E
    • 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
    • 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
    • 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
    • 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
    • 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
    • A61P27/04—Artificial tears; Irrigation solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A61P39/06—Free radical scavengers or antioxidants

Definitions

  • the present invention relates to an ophthalmic composition containing one or more selected from vitamin A and vitamin E.
  • the tear fluid layer is essential for maintaining the function of the eye in order to prevent evaporation of water from tears and to remove foreign substances, and it must be stable on the surface of the eye to fulfill its role. is necessary.
  • This tear oil layer is composed of lipids (meibum) secreted from the meibomian glands, and the main components are wax esters, cholesterol esters, phospholipids and the like. On the other hand, these components increase the percentage of saturated lipids due to aging and hormonal changes, affect the stabilization of the tear fluid layer, increase the evaporation of the tear fluid layer, and cause dry eye symptoms. Furthermore, it is said to have a deep relationship with eye fatigue.
  • lipid saturation proceeds excessively and the above symptoms worsen.
  • the generation of lipid peroxide from the tear fluid layer also induces eye discomfort.
  • the cause of the generation of lipid peroxide from the tear oil layer includes oxidation by light having a short wavelength such as ultraviolet light or blue light. In recent years, it has been considered that the risk of oxidation is increasing because the working time in the VDT equipment, which is the source of blue light, has been prolonged.
  • an antioxidant component In order to suppress the generation of lipid peroxide in the tear fluid layer, it is conceivable to supply an antioxidant component to the tear fluid layer with an ophthalmic composition such as eye drops.
  • an ophthalmic composition such as eye drops.
  • the antioxidant component is not sufficiently transferred to the tear fluid layer and is discharged from the conjunctival sac, and the effect of suppressing lipid peroxide generation is insufficient.
  • the present invention has been made in view of the above circumstances, and vitamin A and vitamin E, which are fat-soluble antioxidant components, are released from the composition by dilution of tears (hereinafter referred to as the release property of the component (A) from the composition). It is an object of the present invention to provide a composition that can be supplied to the tear oil layer, can suppress the generation of lipid peroxide, and can prevent discomfort caused by lipid peroxide.
  • the present inventors have made vitamin A and / or dilute into tears after instillation by using a composition in which the type and ratio of the nonionic surfactant are limited.
  • vitamin E can be released (separated / floated) from the composition and supplied to the tear oil layer.
  • the composition of the present invention can suppress the generation of lipid peroxides, and further, eye fatigue, blurred and blurred eyes caused by lipid peroxides, dry eyes, foreign body sensation, eye pain, and dazzling eyes
  • eye discomfort can be prevented such as heavy eyes, itchy eyes, eye discomfort, eye grease, lacrimation, and hyperemia.
  • the present invention provides the following ophthalmic composition and method for producing the same. [1].
  • A one or more selected from (A-1) vitamin A and (A-2) vitamin E;
  • These blending mass ratios are (A-1) / [(A-1) + (A-2)] ⁇ 0.1, 0.05 ⁇ [(B-1) + (B-2) + (B-3)] / [(A-1) + (A-2)], [(B-1) /0.25+ (B-2) /0.01+ (B-3) /0.1] / [(A-1) + (A-2)] ⁇ (A-1) / [(A-1) + (A-2)] + [(B-1) /0.1+ (B-2) /0.2+ (B-3) /0.05] / [(A-1) + (A-
  • Vitamin A, vitamin E, etc. are released by dilution of tears, they can be sufficiently supplied to the tear oil layer, the generation of lipid peroxide can be suppressed, and further, eye discomfort caused by lipid peroxide can be prevented.
  • An object is to provide an ophthalmic composition and a method for producing the same.
  • vitamin A (A-1) vitamin A and (A-2) vitamin E. These are ingredients known as fat-soluble vitamins.
  • A-1) Vitamin A examples include, in addition to vitamin A itself, vitamin A-containing mixtures such as vitamin A oil, vitamin A derivatives such as vitamin A fatty acid esters, etc., alone or in combination of two or more Can be used. Specific examples include retinol palmitate, retinol acetate, retinol, retinoic acid, and retinoid. Of these, retinol palmitate is preferred.
  • Vitamin E As vitamin E, for example, tocopherol, tocotrienol, their salts, and derivatives (esters) are used as a generic term. Specifically, for example, there are d- ⁇ -tocopherol, dl- ⁇ -tocopherol, ⁇ -tocopherol, ⁇ -tocopherol, ⁇ -tocopherol and the like, and examples of these derivatives include vitamin E acetate (tocopherol acetate). , Vitamin E nicotinic acid ester, vitamin E succinic acid ester, vitamin E linolenic acid ester and the like can be mentioned, and these can be used singly or in appropriate combination of two or more. Of these, tocopherol acetate (d- ⁇ -tocopherol acetate, dl- ⁇ -tocopherol acetate, etc.) is preferable. As the component (A), (A-2) vitamin E is preferable.
  • the total amount of the component (A-1) and the component (A-2) is preferably 0.0001 to 1 W / V% (mass / volume%, g / 100 mL, the same shall apply hereinafter) in the ophthalmic composition.
  • 001 to 0.5 W / V% is more preferable, and 0.01 to 0.1 W / V% is particularly preferable.
  • the antioxidant effect is more exhibited, and when it is 1 W / V% or more, it becomes easy to feel eye irritation.
  • the amount of the component (A-1) is not particularly limited as long as the above ratio is satisfied from the viewpoint of release from the composition, but is preferably 0 to 0.1 W / V% in the composition, / V% may be sufficient. On the other hand, it is preferable to contain 0.005 W / V% or more from a viewpoint of lipid peroxide suppression.
  • the amount of the component (A-2) is not particularly limited as long as it satisfies the above ratio, but is preferably 0.00009 to 1 W / V%, more preferably 0.001 to 0.5 W / V%, and More preferred is 01 to 0.1 W / V%.
  • the (B) nonionic surfactant of the present invention includes (B-1) polyoxyethylene castor oil (may be described as POE castor oil), (B-2) polyoxy It is classified into ethylene hardened castor oil (may be described as POE hardened castor oil), (B-3) other nonionic surfactants, and is one or more nonionic surfactants selected from these.
  • component (B) since the release from the composition can be maintained even when blended at a relatively high concentration, (B-1) the polyoxyethylene castor oil and (B -2) It is preferable to use at least one selected from polyoxyethylene hydrogenated castor oil. Furthermore, it is more preferable that two or more kinds of nonionic surfactants are blended from the viewpoint of composition stability.
  • Polyoxyethylene castor oil (POE castor oil) is a compound obtained by addition polymerization of ethylene oxide to castor oil. The type of is known. The average added mole number of ethylene oxide in the polyoxyethylene castor oil is not particularly limited, but 3 to 60 moles are exemplified. Specifically, polyoxyethylene castor oil 3 (the number is the average number of moles of ethylene oxide added, hereinafter the same), polyoxyethylene castor oil 10, polyoxyethylene castor oil 20, polyoxyethylene castor oil 35, polyoxyethylene castor Examples include oil 40, polyoxyethylene castor oil 50, polyoxyethylene castor oil 60, and the like. These polyoxyethylene castor oils can be used singly or in appropriate combination of two or more. Among these, it is preferable to use polyoxyethylene castor oil 35.
  • the blending amount when blending the component (B-1) is not particularly limited as long as the following ratio is satisfied, but is preferably 0.000001 W / V% or more, more preferably 0.00001 W / V% or more in the composition. . By setting it as the above or more, a composition becomes more uniform. From the viewpoint of safety, 1.0 W / V% or less is preferable.
  • Polyoxyethylene hydrogenated castor oil (POE hydrogenated castor oil) is a compound obtained by addition polymerization of ethylene oxide to hydrogenated castor oil. Several types with different numbers of moles are known. The average added mole number of ethylene oxide in the polyoxyethylene hydrogenated castor oil is not particularly limited, but is exemplified by 5 to 100 moles.
  • polyoxyethylene hydrogenated castor oil 5 (the numerical value is the average number of moles of ethylene oxide added, the same applies hereinafter), polyoxyethylene hydrogenated castor oil 10, polyoxyethylene hydrogenated castor oil 20, polyoxyethylene hydrogenated castor oil 30, Examples include polyoxyethylene hydrogenated castor oil 40, polyoxyethylene hydrogenated castor oil 50, polyoxyethylene hydrogenated castor oil 60, polyoxyethylene hydrogenated castor oil 80, and polyoxyethylene hydrogenated castor oil 100.
  • These polyoxyethylene castor oils can be used singly or in appropriate combination of two or more. Among these, it is preferable to use polyoxyethylene hydrogenated castor oil 40 and polyoxyethylene hydrogenated castor oil 60.
  • the blending amount when blending the component (B-2) is not particularly limited as long as the following ratio is satisfied, but is preferably 0.000001 W / V% or more, more preferably 0.00001 W / V% or more in the composition. . By setting it as the above or more, a composition becomes more uniform. From the viewpoint of safety, 1.0 W / V% or less is preferable.
  • Nonionic surfactants other than (B-1) and (B-2) include polysorbate 80 (polyoxyethylene (20) sorbitan monolaurate) (inside) The values are the average number of moles of ethylene oxide added, the same shall apply hereinafter), polyoxyethylene sorbitan fatty acid ester (POE sorbitan fatty acid ester), poloxamer represented by polyoxyethylene-polyoxypropylene block copolymer (POEPOP glycol), mono Examples include polyethylene glycol monostearate typified by polyethylene glycol stearate (10), and these can be used alone or in combination of two or more.
  • polysorbate 80 polyoxyethylene (20) sorbitan monolaurate
  • POE sorbitan fatty acid ester polyoxyethylene sorbitan fatty acid ester
  • poloxamer represented by polyoxyethylene-polyoxypropylene block copolymer POEPOP glycol
  • mono Examples include polyethylene glycol monostearate typified by polyethylene glycol stearate
  • lecithin, hydrogenated lecithin, and phospholipids such as phosphatidylcholine and phosphatidylglycerol, which are difficult to desorb from the interface, are not separated from vitamin A or / and vitamin E by tear dilution, and are hardly transferred to the tear oil layer. It is preferable not to be included.
  • the blending amount in the case of blending the component (B-3) is not particularly limited as long as the following ratio is satisfied, but is preferably 0.000001 W / V% or more, more preferably 0.00001 W / V% or more in the composition. And by setting it as the above or more, a composition becomes more uniform. From the viewpoint of safety, 0.5 W / V% or less is preferable.
  • the nonionic surfactant of a component is mix
  • the following ratio is W / V% ratio, it becomes the same value as mass ratio.
  • [(B-1) + (B-2) + (B-3)] / [(A-1) + (A-2)] is the blending lower limit of the component (B),
  • B) Defines the amount of nonionic surfactant. Unless 0.05 ⁇ [(B-1) + (B-2) + (B-3)] / [(A-1) + (A-2)] is satisfied, a uniform composition cannot be obtained. The desired transmittance cannot be obtained.
  • the ratio is more preferably 0.1 ⁇ , and further preferably 0.5 ⁇ .
  • the upper limit of [(B-1) + (B-2) + (B-3)] / [(A-1) + (A-2)] is not particularly limited, but the composition of component (A) 2.0 or less is preferable from the viewpoint of releasability from water.
  • the above formula for determining the blending conditions defines the amounts of (B-1), (B-2), and (B-3) relative to (A-1) and (A-2).
  • B Since the blending conditions of (A) differ depending on the type of nonionic surfactant, each is divided by a specific coefficient for the type of component (B). For example, when comparing (B-1) /0.25 and (B-3) /0.1, the intrinsic coefficient of (B-1) is 2.5 times higher than (B-3). It means that.
  • [(B-1) /0.25+ (B-2) /0.01+ (B-3) / 0 .1] represents a formula regarding the upper limit of the amount of each component (B) relative to (A-1)
  • [(B-1) /0.1+ (B-2) /0.2+ (B-3) / 0 .05] represents a formula relating to the upper limit of the amount of each component (B) relative to (A-2). They are divided by the sum of components (A) (A-1) + (A-2).
  • component (A-2) 1.0 W / V%, if (B-1) alone, more than 0.05 W / V%, 1.0 W / V% or less, (B-2) alone If it exists, it is necessary to be more than 0.05 W / V% and not more than 2.0 W / V%, and if it is (B-3) alone, it needs to be more than 0.05 W / V% and 0.5 W / V% or less.
  • Cationic surfactants typified by benzalkonium chloride and benzethonium chloride, anionic surfactants typified by sodium lauryl sulfate and sorbic acid or salts thereof, and amphoteric surfactants typified by lauramine oxide.
  • the agent inhibits separation of the component (A) and the surfactant by dilution of the tears, and the component (A) is less likely to be transferred to the tear fluid layer, so that the content is preferably 0.1 W / V% or less in the composition. , 0.01 W / V% or less is more preferable, and it is particularly preferable that the content is not substantially contained.
  • the ophthalmic composition of the present invention may further contain (C) a terpenoid.
  • a terpenoid By blending the terpenoid, release properties such as enhancing the release properties of the component (A) from the composition can be adjusted, and further, the effect of suppressing the generation of lipid peroxide can be enhanced.
  • the terpenoid in the present invention has a structure having an isoprene unit as a structural unit, and examples thereof include terpene hydrocarbon, terpene alcohol, terpene aldehyde, and terpene ketone. Also, depending on the number of carbons, there are monoterpenes, sesquiterpenes, diterpenes, triterpenes, and tetraterpenes.
  • monoterpenes such as menthol, menthone, camphor, borneol, rünou, geraniol, cineole, linalool, citronellol and limonene, diterpenes such as retinol and retinal, and tetraterpenes such as carotenoids.
  • diterpenes such as retinol and retinal
  • tetraterpenes such as carotenoids.
  • terpenoids can be used in any of d-form, l-form or dl-form.
  • an essential oil containing the above compound may be used as the terpenoid.
  • essential oils include eucalyptus oil, bergamot oil, fennel oil, rose oil, mint oil, peppermint oil, spearmint oil, and essential oils of dipterocarpaceae, rosmarin oil, and lavender oil.
  • Bergamot oil and eucalyptus oil are preferable from the viewpoint of enhancing the release from the composition of the component.
  • the blending amount of the component (C) is 0.0001 to 0.2 W / V% in the composition, and is appropriately selected from the other blending components such as the type of the component (C), the component (B) and the blending amount thereof. 0.001 to 0.1 W / V% is preferable. In this blending concentration range, there is little risk of precipitation of (C) terpenoids regardless of the types and blending amounts of other blending components. Moreover, 0.005 W / V% or more is more preferable from a viewpoint of lipid peroxide generation
  • composition of the present invention An appropriate amount of other components can be blended in the composition of the present invention as long as the effects of the present invention are not impaired.
  • other components include oil components, preservatives, sugars, buffers, pH adjusters, tonicity agents, stabilizers, polyhydric alcohols, thickeners, drugs, and the like. These components can be blended singly or in appropriate combination of two or more.
  • the compounding amount of the components shown below is a preferable range when blending.
  • Oil components include castor oil, soybean oil, olive oil, sesame oil, corn oil, coconut oil, almond oil, medium chain fatty acid triglyceride, white petrolatum, purified lanolin, cholesterol, mixed tocopherol, liquid paraffin, and the like.
  • the blending amount of the oil component is preferably 0.001 to 1.0 W / V% in the composition, more preferably 0.001 to 0.5 W / V%, and most preferably 0.001 to 0.25 W / V%.
  • examples of the preservative having a hydrophobic portion such as an alkyl chain or a benzene ring include thimerosal, phenylethyl alcohol, alkylaminoethylglycine, chlorhexidine gluconic acid, methyl paraoxybenzoate, ethyl paraoxybenzoate, and the like ( Since the component A) is less likely to be transferred to the tear oil layer, the composition preferably has a content of 0.1 W / V% or less, more preferably 0.01 W / V% or less, and even more preferably does not contain substantially.
  • sugars include glucose, cyclodextrin, xylitol, sorbitol, mannitol and the like. In addition, these may be any of d-form, l-form, or dl-form.
  • the blending amount of the saccharide is preferably 0.001 to 5.0 W / V% in the composition, more preferably 0.001 to 1 W / V%, and further preferably 0.001 to 0.1 W / V%.
  • the buffer examples include citric acid, sodium citrate, boric acid, borax, phosphoric acid, sodium hydrogen phosphate, sodium dihydrogen phosphate, glacial acetic acid, trometamol, sodium hydrogen carbonate and the like.
  • the blending amount of the buffer is preferably 0.001 to 5.0 W / V% in the composition, more preferably 0.001 to 2 W / V%, and still more preferably 0.001 to 1 W / V%.
  • an inorganic acid or an inorganic alkali agent can be used as the pH adjusting agent.
  • (diluted) hydrochloric acid is mentioned as an inorganic acid.
  • the inorganic alkaline agent include sodium hydroxide, potassium hydroxide, sodium carbonate, sodium hydrogen carbonate and the like.
  • the pH of the composition is preferably 3.5 to 8.0, more preferably 5.5 to 8.0.
  • the pH is measured at 25 ° C. using a pH meter (HM-25R, Toa DKK).
  • tonicity agents include sodium chloride, potassium chloride, calcium chloride, sodium bicarbonate, sodium carbonate, dry sodium carbonate, magnesium sulfate, sodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, and the like. And isotonic.
  • the osmotic pressure ratio of the composition to physiological saline is preferably 0.60 to 2.00, more preferably 0.60 to 1.55, and most preferably 0.83 to 1.20.
  • the osmotic pressure is measured using an automatic osmometer (A2O, Advanced Instruments) at 25 ° C.
  • the stabilizer examples include sodium edetate, sodium edetate hydrate, cyclodextrin, sulfite, and dibutylhydroxytoluene.
  • the blending amount of the stabilizer is preferably 0.001 to 5.0 W / V% in the composition, more preferably 0.001 to 1 W / V%, and still more preferably 0.001 to 0.1 W / V%.
  • Dibutylhydroxytoluene inhibits the separation of the component (A) and the surfactant due to dilution of tears, and the component (A) is less likely to be supplied to the tear fluid layer.
  • the polyhydric alcohol examples include glycerin, propylene glycol, butylene glycol, and polyethylene glycol.
  • the blending amount of the polyhydric alcohol is preferably 0.001 to 5.0 W / V% in the composition, more preferably 0.001 to 1 W / V%, and 0.001 to 0.00. 1 W / V% is more preferable.
  • the thickener examples include polyvinylpyrrolidone, hydroxyethylcellulose, hydroxypropylmethylcellulose, methylcellulose, polyvinyl alcohol, sodium hyaluronate, sodium chondroitin sulfate, polyacrylic acid, carboxyvinyl polymer, and the like.
  • the blending amount is preferably 0.001 to 5.0 W / V% in the composition, more preferably 0.001 to 1 W / V%, and 0.001 to 0.1 W / V. % Is more preferable.
  • drugs pharmaceutical active ingredients
  • decongestants eg, epinephrine, epinephrine hydrochloride, ephedrine hydrochloride, tetrahydrozoline hydrochloride, naphazoline hydrochloride, naphazoline nitrate, phenylephrine hydrochloride, dl-methylephedrine hydrochloride, etc.
  • Anti-inflammatory / astringent eg, neostigmine methyl sulfate, epsilon-aminocaproic acid, allantoin, berberine chloride hydrate, berberine sulfate hydrate, sodium azulenesulfonate, dipotassium glycyrrhizinate, zinc sulfate, zinc lactate, lysozyme hydrochloride Salt
  • antihistamines eg, diphenhydramine hydrochloride, chlorpheniramine maleate
  • the effective content of each drug can be selected as the drug content, but 0.001 to 5.0 W / V% in the composition is preferable, and 0.001 to 1 W / V% Is more preferable, and 0.001 to 0.1 W / V% is still more preferable.
  • the production method of the composition of the present invention is not particularly limited.
  • a mixed solution of an oil component such as component (A) and a surfactant component such as component (B) is mixed with an aqueous solution containing an aqueous component.
  • the total volume can be obtained with water.
  • the mixing method of each liquid may be a general method, and is appropriately performed using a pulsator, a propeller blade, a paddle blade, a turbine blade, etc., but the rotation speed is not particularly limited and should be set to a level that does not cause intense foaming. Is preferred.
  • the mixing temperature of each liquid is not particularly limited, but it is preferable that both the oily component and the surfactant component are equal to or higher than the melting temperature, and specifically, appropriately selected from the range of 40 to 95 ° C. More preferably, a miniaturization step by high-pressure emulsification is performed. From the viewpoint of improving the clarity of the composition, it is preferable to increase the number of passes at a high pressure, and from the viewpoint of improving production efficiency, it is preferable to reduce the number of passes at a low pressure, and the injection pressure is 100. To 245 MPa is preferable, 150 to 245 MPa is more preferable, and 200 to 245 MPa is more preferable.
  • a back pressure preferably 1 to 10 MPa, more preferably 2 to 5 MPa.
  • the number of passes is preferably 1 to 10 times, and more preferably 1 to 5 times.
  • the temperature during high-pressure emulsification is appropriately selected from the range of 20 to 90 ° C.
  • composition After filling the obtained composition into a resin container, it is further sealed with a package, and an inert gas concentration may be sealed in a space formed between the container and the package.
  • the composition may be filled in a resin container and sealed with a package together with an oxygen scavenger.
  • the composition of the present invention is preferably an “aqueous ophthalmic composition”.
  • the “aqueous ophthalmic composition” refers to an ophthalmic composition in which the medium is water.
  • the amount of water is preferably 90.0 to 99.5 W / V% in the composition from the viewpoint of facilitating mixing with tears and facilitating transfer of the component (A) to tears. It is more preferably 0.0 to 98.0 W / V%.
  • the composition of the present invention is preferably a liquid in terms of facilitating adaptation to the eyes, and the viscosity at 25 ° C. facilitates mixing with tear fluid and facilitates transfer of component (A) to tear fluid. It is preferably 20 mPa ⁇ s or less, more preferably 10 mPa ⁇ s or less, further preferably 5 mPa ⁇ s or less, and particularly preferably 2 mPa ⁇ s or less.
  • the viscosity is measured using a cone plate viscometer (DV2T, Eihiro Seiki Co., Ltd.).
  • the composition of the present invention is preferably clear from the viewpoint of facilitating discovery when foreign matter is mixed.
  • the transmittance at a wavelength of 600 nm measured using a spectrophotometer is 70% or more, preferably 70 to 100%, more preferably 75 to 100%, 90 to 100% is more preferable.
  • the median diameter of the aggregate of the surfactant and the component (A) contained in the composition of the present invention is measured with a particle size measuring device (ELSZ-200ZS, manufactured by Otsuka Electronics Co., Ltd.) to stabilize the composition. From the viewpoint of properties, it is preferably 1 to 200 nm, more preferably 1 to 100 nm, still more preferably 1 to 60 nm, and particularly preferably 1 to 40 nm.
  • the composition of the present invention can be suitably used as eye drops, eye drops for contact lenses, eye wash, etc., but the tear dilution ratio is high, and the release of the surfactant from the component (A) is further promoted. Since the release of the component A) from the composition is improved, and the supply of the component (A) to the tear fluid layer is performed efficiently, eye drops for eye drops and eye drops for contact lenses (eye drops for contact lens wearers) It can be suitably used as an eye drop such as an agent.
  • the contact lens is not particularly limited, such as a hard contact lens or a soft contact lens.
  • the composition of the present invention prevents tear lipid oxidation due to VDT work or ultraviolet rays, etc., and causes eye discomfort due to lipid peroxide (eye fatigue, blurred vision, blurred vision, dry eyes, foreign body sensation, eye pain, (Dazzling eyes, heavy eyes, itchy eyes, eye discomfort, eye oil, lacrimation, hyperemia, etc.) It is effective for preventing unpleasant symptoms, and particularly effective for improving symptoms of eye fatigue, foreign body sensation, eye pain, and eye discomfort.
  • the effective amount, administration method, formulation and the like are as described above.
  • amount of component (A) 0.0001 to 1 mg per adult is divided into 1 to 6 times a day and administered to the eye. To do.
  • % of the composition is W / V%.
  • the ratio is a W / V% ratio, which is the same value as the mass ratio.
  • aqueous component described in the following table was dissolved in 90 mL of water and heated and mixed at 90 ° C. for 15 minutes.
  • a premix of the component (A) and the component (B) was prepared and heated and mixed at 90 ° C. for 15 minutes.
  • a predetermined amount of the premix was added to the aqueous solution, and further heated and mixed at 90 ° C. for 15 minutes. Then, it cooled to room temperature, adjusted pH, and added water so that it might be set to 100 mL.
  • eye drops obtained in each Example had a viscosity at 25 ° C. in the range of 0.5 to 2.0 mPa ⁇ s.
  • the meibomian gland opening near the eyelid (Funakoshi Co., Ltd.) cut out from the rabbit was pressed with a finger, and the extruded meibum was collected with Kimwipe (manufactured by Nippon Paper Crecia Co., Ltd.). Thereafter, the Kimwipe was put in a glass vial, immersed in a 1: 1 mixture (volume ratio) of chloroform and methanol, treated with ultrasonic waves for 10 minutes, and the liquid was transferred to another glass vial. This operation was repeated three times.
  • the mixture was filtered using a Terumo syringe washed with the chloroform / methanol mixed solution (Termo Co., Ltd., 50 mL) and a membrane filter (Merck Millipore Co., Ltd., Millex GP, 0.22 ⁇ m), and the dry weight was precisely balanced. (Measured by Shimadzu Corporation, XS-104). Thereafter, chloroform was added to a concentration of 0.5 mg / mL with a micro syringe (manufactured by Hamilton), the rabbit meibum was dissolved, and stored in a ⁇ 20 ° C. freezer. Upon use, the temperature was returned to room temperature, and it was confirmed that there was no precipitate.
  • aqueous layer is formed with 1 mL of physiological saline on a 35 mm dish, a rabbit meibum chloroform solution (0.5 mg / mL) is spread on the surface of 100 ⁇ L, 165 ⁇ L of each eye drop is added, and irradiated with UV (254 nm) for 1 hour. The whole amount of this solution was collected in a vial.

Abstract

L'invention concerne une composition ophtalmique qui comprend (A) un ou plusieurs élément(s) choisi(s) parmi (A-1) la vitamine A et (A-2) la vitamine E et (B) des tensioactifs non ioniques, et dont le facteur de transmission est supérieur ou égal à 70 %, le rapport massique de composition des ingrédients mentionnés précédemment satisfaisant les exigences suivantes : (A-1)/[(A-1)+(A-2)] ≤ 0,1 ; 0,05 < [(B-1)+(B-2)+(B-3)]/(A) ; et [(B-1)/0,25 + (B-2)/0,01 + (B-3)/0,1]/[(A-1) + (A-2)] × (A-1)/[(A-1) + (A-2)] + [(B-1)/0,1 + (B-2)/0,2 + (B-3)/0,05]/[(A-1) + (A-2)] × (A-2)/[(A-1) + (A-2)]) ≤ 10.
PCT/JP2017/045278 2016-12-19 2017-12-18 Composition ophtalmique et son procédé de fabrication WO2018117014A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
KR1020197006629A KR102453524B1 (ko) 2016-12-19 2017-12-18 안과용 조성물 및 그 제조 방법
JP2018557757A JPWO2018117014A1 (ja) 2016-12-19 2017-12-18 眼科用組成物及びその製造方法

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2016245713 2016-12-19
JP2016-245713 2016-12-19

Publications (1)

Publication Number Publication Date
WO2018117014A1 true WO2018117014A1 (fr) 2018-06-28

Family

ID=62627716

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2017/045278 WO2018117014A1 (fr) 2016-12-19 2017-12-18 Composition ophtalmique et son procédé de fabrication

Country Status (4)

Country Link
JP (1) JPWO2018117014A1 (fr)
KR (1) KR102453524B1 (fr)
TW (1) TWI787221B (fr)
WO (1) WO2018117014A1 (fr)

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6470413A (en) * 1987-05-15 1989-03-15 Santen Pharmaceutical Co Ltd Aqueous preparation of vitamin e
JPH06293639A (ja) * 1993-04-08 1994-10-21 Lion Corp 安定なビタミンａ類及びビタミンｅ類可溶化点眼剤
JP2002104959A (ja) * 2000-09-29 2002-04-10 Lion Corp 眼科用組成物
JP2002356420A (ja) * 2001-03-27 2002-12-13 Santen Pharmaceut Co Ltd 安定な水性液剤
JP2013253063A (ja) * 2012-06-08 2013-12-19 Lion Corp 高吸着性ビタミンａ含有ナノエマルション粒子を含む眼科用組成物及びその製造方法
JP2014028790A (ja) * 2012-06-27 2014-02-13 Rohto Pharmaceut Co Ltd 水性眼科組成物
JP2014129330A (ja) * 2012-06-08 2014-07-10 Lion Corp 粘膜用組成物

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2166722A1 (fr) * 1994-05-06 1995-11-16 Manoj L. Maniar Utilisation de derives tocopheryle de vitamine e dans des compositions ophtalmiques
US6194457B1 (en) * 1997-01-29 2001-02-27 A. Glenn Braswell Liquid eye drop composition
US9012503B2 (en) * 2009-06-25 2015-04-21 Lion Corporation Ophthalmic composition
WO2013183778A1 (fr) * 2012-06-08 2013-12-12 ライオン株式会社 Composition pour membranes muqueuses
JP5873573B2 (ja) * 2012-12-04 2016-03-01 ロート製薬株式会社 水性眼科組成物
JP6260230B2 (ja) * 2013-11-28 2018-01-17 ライオン株式会社 眼科用組成物
JP6225832B2 (ja) * 2014-05-26 2017-11-08 ライオン株式会社 液体組成物及びその製造方法

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6470413A (en) * 1987-05-15 1989-03-15 Santen Pharmaceutical Co Ltd Aqueous preparation of vitamin e
JPH06293639A (ja) * 1993-04-08 1994-10-21 Lion Corp 安定なビタミンａ類及びビタミンｅ類可溶化点眼剤
JP2002104959A (ja) * 2000-09-29 2002-04-10 Lion Corp 眼科用組成物
JP2002356420A (ja) * 2001-03-27 2002-12-13 Santen Pharmaceut Co Ltd 安定な水性液剤
JP2013253063A (ja) * 2012-06-08 2013-12-19 Lion Corp 高吸着性ビタミンａ含有ナノエマルション粒子を含む眼科用組成物及びその製造方法
JP2014129330A (ja) * 2012-06-08 2014-07-10 Lion Corp 粘膜用組成物
JP2014028790A (ja) * 2012-06-27 2014-02-13 Rohto Pharmaceut Co Ltd 水性眼科組成物

Also Published As

Publication number Publication date
KR20190098949A (ko) 2019-08-23
JPWO2018117014A1 (ja) 2019-12-12
KR102453524B1 (ko) 2022-10-12
TWI787221B (zh) 2022-12-21
TW201822761A (zh) 2018-07-01

Similar Documents

Publication Publication Date Title
JP7388418B2 (ja) 眼科用組成物及びその製造方法
KR101690817B1 (ko) 안과용 조성물
JP7047768B2 (ja) 眼科用組成物
WO2013183778A1 (fr) Composition pour membranes muqueuses
JP2009196983A (ja) 眼科用組成物
JP7230825B2 (ja) 水性眼科用組成物及びエマルション粒子の微粒化方法
JP2007169232A (ja) 眼科用組成物
JP5041761B2 (ja) 眼粘膜適用製剤
WO2018117014A1 (fr) Composition ophtalmique et son procédé de fabrication
JP7192766B2 (ja) 眼科用組成物及びその製造方法
JP7467911B2 (ja) 眼科用組成物及び外観安定化方法
KR102665630B1 (ko) 수성 안과용 조성물 및 에멀션 입자의 미립화 방법
JP7139703B2 (ja) 水性眼科用組成物
JP7056480B2 (ja) 眼科用組成物及び涙液油層安定化剤
WO2021246172A1 (fr) Composition ophtalmique, procédé de photostabilisation et procédé de suppression de décoloration
JP2021100918A (ja) 液体組成物、液体組成物の製造方法及び安定化方法
JP2024064436A (ja) 眼科用組成物
JP2020066590A (ja) 水性眼科用組成物及び保存効力向上方法
JP2022099522A (ja) 眼科用組成物及び外観安定化方法

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 17884126

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2018557757

Country of ref document: JP

Kind code of ref document: A

ENP Entry into the national phase

Ref document number: 20197006629

Country of ref document: KR

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 17884126

Country of ref document: EP

Kind code of ref document: A1