WO2018105678A1 - Composition ophtalmologique - Google Patents

Composition ophtalmologique Download PDF

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Publication number
WO2018105678A1
WO2018105678A1 PCT/JP2017/043917 JP2017043917W WO2018105678A1 WO 2018105678 A1 WO2018105678 A1 WO 2018105678A1 JP 2017043917 W JP2017043917 W JP 2017043917W WO 2018105678 A1 WO2018105678 A1 WO 2018105678A1
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WO
WIPO (PCT)
Prior art keywords
oil
liquid paraffin
tear
eye
ophthalmic composition
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PCT/JP2017/043917
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English (en)
Japanese (ja)
Inventor
雅貴 吉田
裕美 高村
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ライオン株式会社
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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 KR1020197004843A priority Critical patent/KR20190093550A/ko
Priority to JP2018555055A priority patent/JP7047768B2/ja
Publication of WO2018105678A1 publication Critical patent/WO2018105678A1/fr

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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
    • A61K31/01—Hydrocarbons
    • 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

Definitions

  • 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 oil layer, increase the evaporation of the tear water layer, and cause dry eye symptoms . Furthermore, it is said to have a deep relationship with eye fatigue.
  • the present invention has been made in view of the above circumstances, and stabilizes the tear oil layer, improves dry eye symptoms, improves eye fatigue symptoms, particularly dry eye caused by tear oil layer destabilization or meibomian gland dysfunction.
  • An object of the present invention is to provide an ophthalmic composition capable of improving symptoms, eye fatigue symptoms, eye fatigue, blurring / haze of eyes, dryness of eyes or fatigue.
  • the present inventors have stabilized the tear oil layer by liquid paraffin, and in particular, improved dry eye symptoms caused by tear oil layer destabilization or meibomian gland dysfunction,
  • the present inventors have found that the present invention has a remarkable effect in improving eye fatigue symptoms, eye fatigue, blurring / haze of eyes, dryness of eyes, or feeling of fatigue, and have led to the present invention.
  • the present invention provides an ophthalmic composition.
  • An ophthalmic composition for stabilizing a tear fluid layer containing liquid paraffin. [2].
  • An ophthalmic composition for improving dry eye symptoms caused by tear film instability or meibomian gland dysfunction, comprising liquid paraffin. [3].
  • An ophthalmic composition for improving eye fatigue, blurred vision, blurred vision, dry eyes or fatigue caused by tear oil layer destabilization or meibomian gland dysfunction, comprising liquid paraffin. [5].
  • the ophthalmic composition according to [1] which is for meibomian gland dysfunction patients. [6].
  • the ophthalmic composition according to [1] which is for dry eye patients or eye fatigue patients caused by tear oil layer destabilization or meibomian gland dysfunction. [7].
  • the tear oil layer stabilization effect in particular, dry eye symptom improvement, eye fatigue, eye blurring and blurring, eye dryness or fatigue caused by tear oil layer instability or meibomian gland dysfunction
  • An ophthalmic composition having a significant effect on feeling improvement can be provided.
  • the present invention is an ophthalmic composition for stabilizing a lacrimal fluid layer containing liquid paraffin, comprising liquid paraffin as an active ingredient, and using liquid paraffin for tear fluid layer stabilization.
  • Liquid paraffin is a component that has a high effect of stabilizing the tear oil layer against the unstable tear oil layer with increased saturated lipids.
  • Liquid paraffin is an oil component having a low polarity compared to vegetable oils and hydrocarbons composed of triglycerides, such as squalane with a short carbon chain length.
  • Liquid paraffin is a mixture of hydrocarbons obtained from crude oil and is liquid at room temperature.
  • the crude oil is produced by a method of performing distillation under reduced pressure and solvent history using raw material of atmospheric distillation residue, followed by solvent refining or hydrocracking.
  • the carbon chain length of the hydrocarbon is not particularly limited, but those of 15 to 45 are preferably used.
  • the hydrocarbon structure may include any of linear, branched and cyclic structures, and any paraffinic liquid paraffin can be used.
  • liquid paraffin and light liquid paraffin listed in the Japanese Pharmacopoeia are suitable.
  • An appropriate type of tocopherol may be included as a stabilizer.
  • the viscosity of liquid paraffin correlates with its molecular weight.
  • a viscosity of 30-100 mm 2 / s is preferable, and a viscosity of 37-88 mm More preferable is 2 / s, and more preferable is 74 to 88 mm 2 / s. You may mix 2 or more types within the said viscosity range.
  • a tear oil layer stabilization effect can be obtained more, and by setting it to 100 mm 2 / s or less, the clarity (transmittance) of the composition is enhanced, Eye irritation peculiar to liquid paraffin can be further reduced.
  • the blending amount of liquid paraffin is preferably 0.001 W / V% (mass / volume%, the same as g / 100 mL or less) or more and less than 100 W / V% in the composition.
  • 0.001 W / V% mass / volume%, the same as g / 100 mL or less
  • 0.001 to 25.0 W / V% is more preferable, 0.001 to 2.5 W / V%, 0.001 to 1.0 W / V%. 0.01 to 0.5 W / V% and 0.05 to 0.25 W / V% are particularly preferable.
  • a tear oil layer stabilization effect can be obtained more, and by setting it to 25.0 W / V% or less, the clarity of the composition is improved and at the same time, an eye peculiar to liquid paraffin Stimulation can be further reduced.
  • an “oil-based ophthalmic composition” in which the medium is mainly an oil component 50.0 W / V% or more is preferable from the viewpoint of appearance stability, more preferably 90.0 W / V% or more, and 99.0 W / V. % Or more is more preferable.
  • the ophthalmic composition of the present invention may further contain a terpenoid.
  • a terpenoid By blending the terpenoid, the liberty can be adjusted, such as increasing the liberation of liquid paraffin to the water surface by dilution of the composition with tear fluid, and the effect of stabilizing the tear fluid layer can be enhanced. Furthermore, the clarity of the composition containing liquid paraffin can be improved.
  • 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.
  • 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.
  • terpenoids can be used in any of d-form, l-form or dl-form.
  • menthol menthone, camphor, borneol, geraniol, cineol and linalool are preferable, and menthol, camphor, borneol, geraniol, cineol and linalool are more preferable.
  • menthol particularly preferred is menthol.
  • essential oils containing the above compounds may be used as terpenoids. Examples of such 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 preferred from the viewpoint of enhancing the effect of stabilizing the tear fluid layer.
  • the amount of terpenoid compounded depends on the type of terpenoid, the type and content of other components (especially surfactants), etc., but the liquid paraffin tear-release properties, tear oil layer stability, and appearance transmittance From the viewpoint of increasing the content, 0.0001 to 0.2 W / V% is preferable in the composition, and 0.005 to 0.1 W / V% is more preferable.
  • 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 surfactants, oil components other than liquid paraffin, preservatives, sugars, buffers, pH adjusters, isotonic agents, stabilizers, polyhydric alcohols, thickeners, drugs, etc. It is done. These components can be blended singly or in appropriate combination of two or more.
  • the compounding quantity of the component shown below is a preferable range in the case of mix
  • nonionic surfactant a nonionic surfactant is preferable.
  • nonionic surfactant include polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, and other nonionic surfactants, which can be used singly or in appropriate combination of two or more.
  • Polyoxyethylene castor oil is a compound obtained by addition polymerization of ethylene oxide to castor oil, and several types are known in which the average added mole number of ethylene oxide is different.
  • the average added mole number of ethylene oxide in the polyoxyethylene castor oil is not particularly limited, but 3 to 60 moles are exemplified.
  • 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.
  • the blending amount is preferably 0.0005 to 20.0 W / V%, more preferably 0.001 to 10.0 W / V%, and 0.0025 to 6.0 W / V V% is more preferable. From the viewpoint of safety, 5.0 W / V% or less is preferable, 2.5 W / V% or less is more preferable, and 1.0 W / V% or less is more preferable.
  • Polyoxyethylene hydrogenated castor oil is a compound obtained by addition polymerization of ethylene oxide to hydrogenated castor oil, and several types with different average addition mole numbers of ethylene oxide are known. ing.
  • 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.
  • the blending amount is preferably 0.0005 to 20.0 W / V%, more preferably 0.0010 to 10.0 W / V%, and 0.0025 to 6.0 W. / V% is more preferable. From the viewpoint of safety, 5.0 W / V% or less is preferable, 2.5 W / V% or less is more preferable, and 1.0 W / V% or less is more preferable.
  • polyoxyethylene sorbitan fatty acid esters represented by polysorbate 80 (polyoxyethylene (20) sorbitan monolaurate) (the values in parentheses are the average number of moles of ethylene oxide added, the same applies hereinafter) (POE sorbitan fatty acid ester), polyoxyethylene-polyoxypropylene block copolymer (POEPOP glycol) typified by poloxamer, and polyethylene glycol monostearate typified by polyethylene glycol monostearate (10).
  • polysorbate 80 polyoxyethylene (20) sorbitan monolaurate
  • POE sorbitan fatty acid ester polyoxyethylene-polyoxypropylene block copolymer
  • POEPOP glycol polyoxyethylene-polyoxypropylene block copolymer
  • polyethylene glycol monostearate typified by polyethylene glycol monostearate (10).
  • the blending amount is not particularly limited as long as the following ratio is satisfied, but preferably 0.5 W / V% or less in the composition, and 0.4 W / V% or less. preferable.
  • 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 liquid paraffin and the surfactant by dilution of the tear, and the liquid paraffin is less likely to be transferred to the tear oil layer. Therefore, the content is preferably 0.1 W / V% or less in the composition. It is more preferable to set it to 0.01 W / V% or less, and it is more preferable not to contain substantially.
  • oil components other than liquid paraffin castor oil, soybean oil, olive oil, sesame oil, corn oil, coconut oil, almond oil, medium chain fatty acid triglyceride, acetic acid-d- ⁇ -tocopherol, retinol palmitate, white petrolatum, refined lanolin , Cholesterol, mixed tocopherol and the like.
  • the blending amount is preferably 0.001 to 1.0 W / V%, more preferably 0.001 to 0.5 W / V%, and 0.001 to 0.25 W / V V% is most preferred.
  • 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, and ethyl paraoxybenzoate. Since it becomes difficult for paraffin to be transferred to the tear oil layer, it is preferably 0.1 W / V% or less, more preferably 0.01 W / V% or less, and even more preferably substantially not contained in the composition.
  • 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 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%. Further preferred.
  • 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 is preferably 0.001 to 5.0 W / V% in the composition, more preferably 0.001 to 2 W / V%, and further 0.001 to 1 W / V%. preferable.
  • 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, from the viewpoint of further improving various symptoms caused by tear film instability.
  • 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. Can be mentioned. From the viewpoint of further improving various symptoms caused by the tear fluid layer destabilization, it is preferable that at least one sodium chloride and potassium chloride are blended to make it 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, more preferably 0.83 from the viewpoint of further improving various symptoms caused by tear fluid layer instability. Most preferred is ⁇ 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 is preferably 0.001 to 5.0 W / V%, more preferably 0.001 to 1 W / V%, and 0.001 to 0.1 W / V in the composition. % Is more preferable.
  • Dibutylhydroxytoluene inhibits separation of liquid paraffin and surfactant due to dilution of tears, and liquid paraffin is less likely to be transferred to the tear oil 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%, more preferably 0.001 to 1 W / V% in the composition, 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. 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 method for producing the composition of the present invention is not particularly limited.
  • a mixed solution of an oil component such as liquid paraffin and a surfactant component is mixed with an aqueous solution containing an aqueous component and emulsified.
  • the volume can be obtained by preparing 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 further refinement step by high-pressure emulsification is performed.
  • the high-pressure emulsification conditions are preferably a high pressure to increase the number of passes from the viewpoint of improving formulation clarity, 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. It is preferably 150 to 245 MPa, more preferably 200 to 245 MPa.
  • 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.
  • each component is mixed at 50 to 90 ° C. with a pulsator, propeller blade, paddle blade, turbine blade, etc., and after dissolution is confirmed, the final volume is 100 mL with liquid paraffin. A method is mentioned.
  • the obtained composition after filling the obtained composition into a resin container, it may be further sealed with a package, and the inert gas concentration in the space formed between the container and the package may be enclosed.
  • 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 may be an “aqueous ophthalmic composition” in which the medium is water or an “oil-based ophthalmic composition” in which the medium is mainly an oil component. From the viewpoint of reducing the peculiar eye irritation of liquid paraffin, it is preferably an “aqueous ophthalmic composition”.
  • the amount of water is easily mixed with tear fluid to prevent delay of liquid paraffin transfer, From the viewpoint of obtaining a liquid oil layer stabilizing effect, the content is preferably 90.0 to 99.5 W / V%, more preferably 95.0 to 98.0 W / V%.
  • the composition of the present invention is preferably a liquid from the viewpoint of facilitating adaptation to the eyes, and the viscosity at 25 ° C. facilitates mixing with tear fluid, prevents delaying the transition to liquid paraffin, and further improves the effect of stabilizing the tear film. From the viewpoint, 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 (for example, 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 in, and preferably has a higher transmittance of the appearance of the composition.
  • the transmittance at a wavelength of 600 nm measured using a spectrophotometer is preferably 50 to 100%, more preferably 75 to 100%, and further 90 to 100%. preferable.
  • the median diameter of the aggregate of surfactant and liquid paraffin contained in the composition of the present invention was measured with a particle size measuring device (ELSZ-200ZS, manufactured by Otsuka Electronics Co., Ltd.), and the stability of the formulation To 1 to 200 nm, preferably 1 to 100 nm, more preferably 1 to 60 nm, and most preferably 1 to 40 nm.
  • ELSZ-200ZS particle size measuring device
  • composition of the present invention can be suitably used as eye drops, eye drops for contact lenses, eye washes, etc., but has a high tear dilution ratio, facilitates the release of surfactant from liquid paraffin, and delivers liquid paraffin.
  • the contact lens is not particularly limited, such as a hard contact lens or a soft contact lens.
  • 10 to 100 ⁇ L each time 1 to 3 drops 1 to 6 times a day, and overflowing from the eyes can stabilize the tear oil layer. Since there is a risk of reduction, 10 to 50 ⁇ L is preferably 1 to 3 drops per day, 1 to 6 times per day, more preferably 10 to 30 ⁇ L per time and 1 to 3 drops 1 to 6 times per day. When used as an eye wash, it is preferable to wash 3 to 6 mL per day and 3 to 6 times per day.
  • composition for stabilizing tear oil layer does not merely replenish the tear oil layer or promote the production of oil components from the meibomian gland, but stabilizes the tear oil layer destabilized by meibomian gland dysfunction or the like Is. Simply promoting the production of the oil component will increase the saturated lipids and make the symptom worse, and it will not be possible to stabilize the depleted tear oil layer simply by replenishing the tear oil layer.
  • the composition of the present invention is effective as a tear fluid layer stabilization (tear fluid layer stabilizer), and further, dry eye symptoms (eye fatigue, blurred vision, blurred vision, dry eyes, foreign body sensation, eye (For pain in the eyes, dazzling eyes, heavy eyes, itchy eyes, discomfort in the eyes, greasy, lacrimation, hyperemia, etc.) and symptoms of eye fatigue (eye fatigue, fatigue, stiff shoulders, headache, etc.) It is effective as an agent for improving dry eye symptoms. In particular, it is effective for improving dry eye symptoms and eye fatigue symptoms caused by destabilization of the tear fluid layer (eye fatigue, blurring / haze of eyes, dryness of eyes or fatigue).
  • More effective symptoms are eye fatigue, blurred eyes and blurred vision, dry eyes, and tiredness, and more effective symptoms are eye fatigue and blurred eyes and blurred vision. It is blurry and blurred.
  • meibomian gland dysfunction patients dry eye patients, eye fatigue patients, especially for dry eye patients caused by tear oil layer destabilization or meibomian gland dysfunction, tear oil layer destabilization or meibom Useful for patients with eye fatigue caused by glandular dysfunction. Since contact lens wearing promotes meibomian gland dysfunction, it is preferably used for contact lens wearers, particularly for soft contact lens wearers.
  • Effective amount, administration method, formulation, etc. are as described above. For example, as an amount of liquid paraffin, 0.01 to 1 mg per adult is divided into 1 to 6 times a day and administered to the eye.
  • Examples 1, 3 to 14, Comparative Examples 3 and 4 Each aqueous component described in the following table was dissolved in 90 mL of water and heated and mixed at 90 ° C. for 15 minutes. At the same time, a premix of liquid paraffin, castor oil, lecithin, sesame oil, petrolatum, retinol palmitate, tocopherol acetate or terpenoid and polyoxyethylene castor oil was prepared and heated and mixed at 90 ° C. for 15 minutes. Next, a predetermined amount of the premix was added to the aqueous solution, and further heated and mixed at 90 ° C. for 15 minutes.
  • Example 2 Comparative Examples 5 to 7
  • Each component of the composition described in the following table was stirred at 60 ° C. using a propeller blade, and after confirmation of dissolution, an eye drop was prepared using liquid paraffin to a final volume of 100 mL or the like.
  • the viscosity of each example was in the range of 0.5 to 2.0 mPa ⁇ s.
  • DR-1 dry eye observation device
  • Oil layer BUT which was 10 seconds or less does not exceed 10 seconds in intraocular and day-to-day fluctuations, and no ophthalmic solution containing liquid paraffin, and improvement to 10 seconds or more is considered to be sufficiently useful. It was judged. [Evaluation criteria] ⁇ (excellent): Oil layer BUT is 60 seconds or more ⁇ (good): Oil layer BUT is 30 seconds or more and less than 60 seconds ⁇ (possible): Oil layer BUT is 10 seconds or more and less than 30 seconds x (Not possible): Oil layer BUT is less than 10 seconds
  • Practical visual acuity is an index representing changes in visual acuity over time, and was measured with a practical visual acuity meter (manufactured by Kowa Co., Ltd.). Each subject was instilled with 30 ⁇ L of each eye drop and 10 minutes later, the initial visual acuity was measured by normal visual acuity measurement, and the visual acuity measurement was continuously performed for 1 minute, and the average was defined as the average visual acuity.
  • ⁇ log visual acuity log initial visual acuity ⁇ log average visual acuity, and visual acuity variation was evaluated.
  • the ophthalmic composition of the present invention has an effect of improving blurring and haze in subjects with meibomian gland dysfunction.
  • the ophthalmic composition of the present invention even after loading, the same result as before loading is obtained, for subjects with meibomian gland dysfunction, "eye fatigue”, “eye blurring and blurring”, The effect of improving “dry eyes” and “feeling of fatigue” was confirmed.

Abstract

Une composition ophtalmologique qui stabilise la couche lipidique du film lacrymal et contient de la paraffine liquide.
PCT/JP2017/043917 2016-12-08 2017-12-07 Composition ophtalmologique WO2018105678A1 (fr)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019111917A1 (fr) * 2017-12-07 2019-06-13 ライオン株式会社 Composition ophtalmologique aqueuse, et procédé d'atomisation de particules en émulsion
WO2020085190A1 (fr) * 2018-10-24 2020-04-30 ライオン株式会社 Composition ophtalmique aqueuse et procédé pour améliorer la durée de conservation
WO2020138135A1 (fr) * 2018-12-26 2020-07-02 ライオン株式会社 Composition à usage ophtalmique

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH10218760A (ja) * 1997-02-04 1998-08-18 Nobel Igaku Kenkyusho:Kk ドライアイ治療用の微量油添加目薬
JP2008222638A (ja) * 2007-03-13 2008-09-25 Teika Seiyaku Kk 油成分含有眼用組成物
JP2008273959A (ja) * 2007-04-04 2008-11-13 Taisho Pharmaceutical Co Ltd 点眼剤
JP2010120856A (ja) * 2008-11-17 2010-06-03 Santen Pharmaceut Co Ltd 眼科用組成物

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002212107A (ja) * 2001-01-22 2002-07-31 Taisho Pharmaceut Co Ltd 局所適用組成物
JP5748385B2 (ja) 2006-01-13 2015-07-15 大正製薬株式会社 Ｏ／ｗ型エマルション水性点眼剤
US20140302146A1 (en) * 2011-07-08 2014-10-09 Rohto Pharmaceutical Co.,Ltd. Ophthalmic Aqueous Composition
JP2016185940A (ja) * 2014-06-10 2016-10-27 ロート製薬株式会社 眼科用組成物

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH10218760A (ja) * 1997-02-04 1998-08-18 Nobel Igaku Kenkyusho:Kk ドライアイ治療用の微量油添加目薬
JP2008222638A (ja) * 2007-03-13 2008-09-25 Teika Seiyaku Kk 油成分含有眼用組成物
JP2008273959A (ja) * 2007-04-04 2008-11-13 Taisho Pharmaceutical Co Ltd 点眼剤
JP2010120856A (ja) * 2008-11-17 2010-06-03 Santen Pharmaceut Co Ltd 眼科用組成物

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019111917A1 (fr) * 2017-12-07 2019-06-13 ライオン株式会社 Composition ophtalmologique aqueuse, et procédé d'atomisation de particules en émulsion
WO2020085190A1 (fr) * 2018-10-24 2020-04-30 ライオン株式会社 Composition ophtalmique aqueuse et procédé pour améliorer la durée de conservation
JP2020066590A (ja) * 2018-10-24 2020-04-30 ライオン株式会社 水性眼科用組成物及び保存効力向上方法
CN112823024A (zh) * 2018-10-24 2021-05-18 狮王株式会社 水性眼科用组合物和提高保存效果的方法
JP7172438B2 (ja) 2018-10-24 2022-11-16 ライオン株式会社 水性眼科用組成物及び保存効力向上方法
WO2020138135A1 (fr) * 2018-12-26 2020-07-02 ライオン株式会社 Composition à usage ophtalmique

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