JP2017197527A - Ophthalmic composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an ophthalmic composition comprising terpenoid, retinol, and/or paraben and having suppressed wettability against a container.SOLUTION: According to the present invention, there is provided an ophthalmic composition comprising one or more selected from the group consisting of terpenoid, retinols, and/or paraben. The ophthalmic composition is contained in a container. Part or whole of the container in contact with the ophthalmic composition is made of resin comprising cyclic olefins.SELECTED DRAWING: None

Description

  The present invention relates to ophthalmic compositions.

  Terpenoids, retinol and / or parabens may be incorporated into ophthalmic compositions (eg, Patent Documents 1, 2, and 3).

  On the other hand, containers made of polypropylene, polyethylene, and polyethylene terephthalate are widely used as containers for storing ophthalmic pharmaceutical preparations (for example, Patent Document 4).

JP 2011-21002 A International Publication No. 2005/0255539 JP-T-2002-527391 JP 2009-196988 A

  The present inventor has found a new problem that when the ophthalmic composition contains a terpenoid, retinol and / or paraben, the dynamic contact angle with a widely used resin is small and easy to wet. If the container formed of these resins is easily wetted, liquid residue may be generated or liquid drainage may be deteriorated, which may cause deterioration in quality of ophthalmic composition and use performance. is there.

  An object of the present invention is to provide an ophthalmic composition containing terpenoids, retinol and / or parabens and having reduced wetting with respect to a container.

  In the ophthalmic composition containing one or more selected from the group consisting of (A) terpenoids, retinols, and parabens, the present inventor is widely used a container formed of a resin containing cyclic olefins. It has been found that the dynamic contact angle is increased (ie, wetting is suppressed) as compared with a container formed of resin.

  In addition, when the ophthalmic composition containing the component (A) is contained in a container formed of a resin containing a cyclic olefin, the inventor reduces the fragrance or deteriorates the odor during storage. In view of this, an ophthalmic composition further containing (B) a buffering agent unexpectedly retains fragrance or suppresses odor changes such as improving odor. I found.

  The present invention is based on this finding and provides the following inventions.

[1]
(A) An ophthalmic composition containing one or more selected from the group consisting of terpenoids, retinols, and parabens, wherein a part or all of the portion in contact with the ophthalmic composition contains a cyclic olefin An ophthalmic composition comprising a container formed of
[2]
The ophthalmic composition according to [1], wherein the resin forming the container further contains polyethylene.
[3]
(B) The ophthalmic composition according to [1] or [2], further comprising a buffer.
[4]
The ophthalmic composition according to any one of [1] to [3], in which the total content of the component (A) is 0.00001 to 1.0 w / v% based on the total amount of the ophthalmic composition.
[5]
The ophthalmic composition according to any one of [1] to [4], wherein the total content of the component (B) is 0.001 to 5000 parts by mass with respect to 1 part by mass of the total content of the component (A). object.
[6]
The ophthalmic composition according to any one of [1] to [5], wherein the pH of the ophthalmic composition is 4.0 to 9.5.
[7]
The ophthalmic composition according to any one of [1] to [6], wherein the water content is 80 w / v% or more and less than 100 w / v% based on the total amount of the ophthalmic composition.
[8]
The ophthalmologic according to any one of [1] to [7], wherein the maximum value of light transmittance in a visible light region having a wavelength of 400 to 700 nm of a container formed of a resin containing cyclic olefins is 50% or more. Composition.
[9]
The ophthalmic composition according to any one of [1] to [8], wherein a drop amount per drop is 1 to 99 μL.
[10]
The ophthalmic composition according to any one of [1] to [9], wherein the number of uses is small or single.
[11]
The ophthalmic composition is provided with one or more selected from the group consisting of (A) terpenoids, retinols, and parabens, and the ophthalmic composition is provided with a wetting inhibitory action on a resin containing a cyclic olefin. how to.
[12]
To an ophthalmic composition housed in a container formed of a resin containing cyclic olefins, (A) one or more selected from the group consisting of terpenoids, retinols, and parabens, and (B) a buffering agent A method of imparting an odor change inhibiting action to the ophthalmic composition, comprising blending.

  Since the ophthalmic composition of the present invention is accommodated in a container formed of a resin containing cyclic olefins, compared to an ophthalmic composition accommodated in a container formed of a widely used resin, The dynamic contact angle is increased (wetting is suppressed). Thereby, the liquid residue of an ophthalmic composition is suppressed and there exists an effect that liquid drainage improves. Thereby, the fall of the quality of an ophthalmic composition and the fall of use performance can be suppressed.

  When the ophthalmic composition of the present invention further contains (B) a buffering agent, the ophthalmic composition containing the component (A) may be contained in a container formed of a resin containing cyclic olefins. It has the effect of suppressing changes in odor, such as maintaining fragrance or improving odor.

  Hereinafter, embodiments for carrying out the present invention will be described in detail. However, the present invention is not limited to the following embodiments.

  In the present specification, unless otherwise specified, the unit of content “%” means “w / v%” and is synonymous with “g / 100 mL”. In the present specification, unless otherwise specified, the abbreviation “POE” means polyoxyethylene, and the abbreviation “POP” means polyoxypropylene.

[1. Ophthalmic composition)
The ophthalmic composition according to the present embodiment contains (A) one or more selected from the group consisting of terpenoids, retinols, and parabens (also simply referred to as “(A) component”).

<(A) component>
Terpenoids include cyclic terpenes and acyclic terpenes, and are not particularly limited as long as they are pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable.

  Cyclic terpenes are terpenoids having at least one ring structure in the molecule. Examples of the cyclic terpene include camphor, borneol (also referred to as “ryuunou”), menthone, cineol, carvone, anethole, eugenol, limonene, pinene, and derivatives thereof.

  Acyclic terpenes are terpenoids that do not have a ring structure in the molecule. Examples of the acyclic terpene include geraniol, citronellol, linalool, linalyl acetate, and derivatives thereof.

  In the present invention, an essential oil containing the above compound may be used as a terpenoid. Examples of such essential oils include eucalyptus oil, bergamot oil, peppermint oil, cool mint oil, spearmint oil, peppermint oil, fennel oil, cinnamon oil, and rose oil.

  The terpenoid may be any of d-form, l-form and dl-form, and includes dl-camphor, d-camphor, l-camphor, dl-borneol, d-borneol, l-borneol, dl-menton, d-menton, and l-menton. Is exemplified. However, optical isomers may not exist depending on terpenoids such as geraniol and cineol.

  Terpenoids preferably do not contain menthol. As the terpenoid, camphor, borneol, menthone and eucalyptus oil are preferable, and dl-camphor, d-borneol, menthone and eucalyptus oil are more preferable.

  Commercially available terpenoids can also be used. A terpenoid may be used individually by 1 type, or may be used in combination of 2 or more type.

  When the terpenoid is contained as the component (A), the content of the terpenoid in the ophthalmic composition according to the present embodiment is, for example, based on the total amount of the ophthalmic composition from the viewpoint of more prominently achieving the effects of the present invention. The total terpenoid content is preferably 0.00005 to 1 w / v%, more preferably 0.0001 to 0.5 w / v%, and 0.001 to 0.1 w / v%. Is more preferably 0.001 to 0.08 w / v%, particularly preferably 0.002 to 0.07 w / v%, and 0.002 to 0.06 w / v%. Is more particularly preferable, 0.003 to 0.05 w / v% is further particularly preferable, and 0.003 to 0.03 w / v% is most preferable.

  When the camphor is contained as the component (A), the content of camphor in the ophthalmic composition according to the present embodiment is, for example, based on the total amount of the ophthalmic composition from the viewpoint of further prominently achieving the effects of the present invention. The total content of camphor is preferably 0.00005 to 1 w / v%, more preferably 0.0001 to 0.5 w / v%, and 0.001 to 0.1 w / v%. More preferably it is.

  In the case where borneol is contained as the component (A), the content of borneol in the ophthalmic composition according to the present embodiment is, for example, based on the total amount of the ophthalmic composition from the viewpoint of further prominent effects according to the present invention. The total content of borneol is preferably 0.0001 to 0.8 w / v%, more preferably 0.0005 to 0.6 w / v%, and 0.001 to 0.5 w / v. % Is more preferable.

  (A) In the case of containing menton as a component, the content of menthone in the ophthalmic composition according to the present embodiment is, for example, based on the total amount of the ophthalmic composition from the viewpoint of further prominent effects of the present invention. The total content of menthone is preferably 0.00001 to 0.5 w / v%, more preferably 0.00005 to 0.1 w / v%, and 0.0001 to 0.05 w / v. % Is more preferable.

  When the eucalyptus oil is contained as the component (A), the content of the eucalyptus oil in the ophthalmic composition according to the present embodiment is, for example, the total amount of the ophthalmic composition from the viewpoint of exhibiting the effects of the present invention more remarkably. As a reference, the total content of eucalyptus oil is preferably 0.00001 to 0.1 w / v%, more preferably 0.00005 to 0.05 w / v%, and 0.0001 to 0.00. More preferably, it is 01 w / v%.

  Retinols include retinol and its derivatives. Examples of the retinol derivative include retinol palmitate, retinol acetate, and the like. In the present invention, vitamin A oil containing the above-mentioned retinol derivative may be used as retinols. As retinols, retinol palmitate is preferred.

  Commercially available retinols can also be used. A retinol may be used individually by 1 type, or may be used in combination of 2 or more type.

  (A) When using retinol as a component, as content of retinol, for example, the total content of retinol is 1 to 500,000 I.D. U. / 100 mL, preferably 500 to 300,000 I.D. U. / 100 mL is more preferable, and 100 to 300,000 I.D. U. / 100 mL, more preferably 500 to 200,000 I.D. U. Particularly preferred is / 100 mL. I.I. U. Means the international unit required by the method described in the 16th revision Japanese Pharmacopoeia Vitamin A Determination Method and the like. For example, according to the 16th revision of the Japanese Pharmacopoeia, the content of retinol acetate must be 2.5 million units or more (1 unit = 0.40 μg or less) per gram, and retinol palmitate per gram. It is a content of 1.5 million units or more (1 unit = 0.667 μg or less), and in the case of vitamin A oil, it is a content of 30,000 units or more (1 unit = 33.3 μg or less) per 1 g. It is prescribed.

  Paraben is a general term for paraoxybenzoic acid esters, and examples thereof include methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, and butyl paraoxybenzoate.

  A commercially available paraben can also be used. A paraben may be used individually by 1 type, or may be used in combination of 2 or more type.

  In the case of containing parabens as the component (A), the content of parabens in the ophthalmic composition according to the present embodiment is, for example, based on the total amount of the ophthalmic composition from the viewpoint of more prominently achieving the effects of the present invention. The total paraben content is preferably 0.0001 to 1.0 w / v%, more preferably 0.001 to 0.5 w / v%, and 0.001 to 0.5 w / v%. More preferably.

  As the component (A), one type may be used alone, or two or more types may be used in combination.

  Content of (A) component in the ophthalmic composition which concerns on this embodiment is not specifically limited, According to the kind of (A) component, the kind and content of another compounding component, the use, formulation form, etc. of an ophthalmic composition Is set as appropriate. The content of the component (A) is, for example, from the viewpoint of more prominently achieving the effects of the present invention, for example, based on the total amount of the ophthalmic composition, the total content of the component (A) is 0.00001 to 1.0 w. / V% is preferable, 0.00005 to 0.9 w / v% is more preferable, 0.0001 to 0.7 w / v% is further preferable, and 0.001 to 0.5 w is preferable. / V% is still more preferred, 0.001 to 0.25 w / v% is particularly preferred, 0.001 to 0.20 w / v% is even more preferred, 0.001 to It is more particularly preferably 0.15 w / v%, particularly preferably 0.001 to 0.12 w / v%, more particularly preferably 0.001 to 0.08 w / v%, .001 to 0.06 w / It is most preferably%.

<(B) component>
The ophthalmic composition according to this embodiment preferably further contains (B) a buffer (also simply referred to as “component (B)”). The effect by this invention is more notably show | played because an ophthalmic composition further contains (B) component. Moreover, even when the ophthalmic composition further contains the component (B), the ophthalmic composition containing the component (A) is contained in a container formed of a resin containing cyclic olefins. The effect of suppressing the change of odor, such as maintaining aromaticity or improving odor, is achieved. The buffering agent is not particularly limited as long as it includes an inorganic buffering agent and an organic buffering agent and is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable.

  An inorganic buffer is a buffer derived from an inorganic acid. Examples of the inorganic buffer include borate buffer, phosphate buffer, and carbonate buffer.

  Examples of the boric acid buffer include boric acid or a salt thereof (alkali metal borate, alkaline earth metal borate, etc.). Examples of the phosphate buffer include phosphoric acid or a salt thereof (such as an alkali metal phosphate or an alkaline earth metal phosphate). Examples of the carbonate buffer include carbonic acid or a salt thereof (an alkali metal carbonate, an alkaline earth metal carbonate, etc.). Moreover, you may use the borate or the hydrate of a phosphate as a borate buffer or a phosphate buffer. As a more specific example, boric acid or a salt thereof (sodium borate, potassium tetraborate, potassium metaborate, ammonium borate, borax, etc.); as a phosphate buffer, phosphoric acid or a salt thereof Salt (disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, trisodium phosphate, tripotassium phosphate, calcium monohydrogen phosphate, calcium dihydrogen phosphate, etc.); Or the salt (Sodium hydrogencarbonate, sodium carbonate, ammonium carbonate, potassium carbonate, calcium carbonate, potassium hydrogencarbonate, magnesium carbonate etc.) etc. can be illustrated.

  The organic buffer is a buffer derived from an organic acid or an organic base. Examples of the organic buffer include citrate buffer, acetate buffer, Tris buffer, epsilon aminocaproate buffer, and AMPD buffer.

  Examples of the citrate buffer include citric acid or salts thereof (alkali metal citrate, alkaline earth metal citrate, etc.). Examples of the acetate buffer include acetic acid or a salt thereof (alkali metal acetate, alkaline earth metal acetate, etc.). Moreover, you may use the hydrate of a citrate or acetate as a citrate buffer or an acetate buffer. As a more specific example, citric acid or a salt thereof (sodium citrate, potassium citrate, calcium citrate, sodium dihydrogen citrate, disodium citrate, etc.); Or the salt (Ammonium acetate, potassium acetate, calcium acetate, sodium acetate etc.) etc. can be illustrated. As a tris buffer, trometamol or its salt (trometamol hydrochloride etc.) is mentioned, for example. Examples of the epsilon aminocaproic acid buffer include epsilon aminocaproic acid or a salt thereof. Examples of the AMPD buffer include 2-amino-2-methyl-1,3-propanediol or a salt thereof.

  Among these buffers, borate buffer (for example, a combination of boric acid and borax), phosphate buffer (for example, a combination of disodium hydrogen phosphate and sodium dihydrogen phosphate), epsilon aminocaproic acid Buffers (eg, epsilon aminocaproic acid), Tris buffers (eg, trometamol), and AMPD buffers (eg, 2-amino-2-methyl-1,3-propanediol) are preferred.

  A commercially available buffer can also be used. A buffering agent may be used individually by 1 type, or may be used in combination of 2 or more type.

  In the ophthalmic composition according to this embodiment, the content of the component (B) is not particularly limited. It is set accordingly. The content of the component (B) is, for example, from the viewpoint of more prominently achieving the effects of the present invention, for example, based on the total amount of the ophthalmic composition, the total content of the component (B) is 0.0001 to 9 w / v. %, More preferably 0.001 to 9 w / v%, still more preferably 0.005 to 8 w / v%, and further preferably 0.01 to 8 w / v%. It is more preferable, and it is especially preferable that it is 0.01-6 w / v%.

  In the ophthalmic composition according to the present embodiment, the content ratio of the component (B) to the component (A) is not particularly limited, the types of the components (A) and (B), the types and contents of other compounding components, It is appropriately set according to the use and formulation form of the ophthalmic composition. When the terpenoid and / or paraben is contained as the component (A), the content ratio of the component (B) relative to the terpenoid and / or paraben is, for example, according to the present embodiment from the viewpoint of more prominently achieving the effects of the present invention. It is preferable that the total content of component (B) is 0.001 to 5000 parts by mass with respect to 1 part by mass of the total content of terpenoids and / or parabens contained in the ophthalmic composition, and 0.01 to 1000 More preferably, it is 0.1 to 800 parts by mass, still more preferably 0.5 to 600 parts by mass, and particularly preferably 0.5 to 500 parts by mass. It is preferably 0.5 to 400 parts by mass, more preferably 1 to 300 parts by mass, and most preferably 1 to 200 parts by mass. Preferred. When the retinol is contained as the component (A), the content ratio of the component (B) relative to the retinol is included in the ophthalmic composition according to the present embodiment, for example, from the viewpoint of more prominently achieving the effects of the present invention. The total content of component (B) is preferably 0.00000001 to 0.1 parts by mass, and 0.00000005 to 0.05 parts by mass with respect to 1 part by mass of the total content of retinols. Is more preferably 0.0000005 to 0.01 part by mass, and still more preferably 0.000005 to 0.006 part by mass.

  The ophthalmic composition according to the present embodiment may further contain a nonionic surfactant. The effect by this invention is show | played more notably because an ophthalmic composition contains a nonionic surfactant further.

  Specific examples of the nonionic surfactant include, for example, monolauric acid POE (20) sorbitan (polysorbate 20), monopalmitic acid POE (20) sorbitan (polysorbate 40), and monostearic acid POE (20) sorbitan (polysorbate 60). POE sorbitan fatty acid esters such as tristearic acid POE (20) sorbitan (polysorbate 65), monooleic acid POE (20) sorbitan (polysorbate 80); POE (5) hydrogenated castor oil (polyoxyethylene hydrogenated castor oil 5) POE (10) hydrogenated castor oil (polyoxyethylene hydrogenated castor oil 10), POE (20) hydrogenated castor oil (polyoxyethylene hydrogenated castor oil 20), POE (30) hydrogenated castor oil (polyoxyethylene hydrogenated castor oil 30) ), POE (4 ) Hydrogenated castor oil (polyoxyethylene hydrogenated castor oil 40), POE (60) hydrogenated castor oil (polyoxyethylene hydrogenated castor oil 60), POE (80) hydrogenated castor oil (polyoxyethylene hydrogenated castor oil 80), POE ( 100) POE hydrogenated castor oil such as hydrogenated castor oil (polyoxyethylene hydrogenated castor oil 100); POE (3) castor oil (polyoxyethylene castor oil 3), POE (10) castor oil (polyoxyethylene castor oil 10) POE castor oil such as POE (35) castor oil (polyoxyethylene castor oil 35), POE (70) castor oil (polyoxyethylene castor oil 70); POE alkyl ether such as POE (9) lauryl ether; POE ( 20) POE (4) POE-POP alkyl ethers such as cetyl ether; POE ( 0) POP (20) Glycol (Pluronic L44), POE (42) POP (67) Glycol (Poloxamer 403, Pluronic P123), POE (54) POP (39) Glycol (Poloxamer 235, Pluronic P85), POE (120) POP (40) Glycol (Pluronic F87), POE (160) POP (30) Glycol (Poloxamer 188, Pluronic F68), POE (196) POP (67) Glycol (Poloxamer 407, Pluronic F127), POE (200) POP ( 70) POE / POP glycol such as glycol; monostearate polyethylene glycol such as polyoxyl stearate 10 and polyoxyl 40 stearate; In the compounds exemplified above, the numbers in parentheses indicate the number of added moles.

  As the nonionic surfactant, POE sorbitan fatty acid esters, polyoxyethylene hydrogenated castor oil, polyoxyethylene castor oil, POE / POP glycol and polyethylene glycol monostearate are preferable. Polysorbate 80, polyoxyethylene hydrogenated castor oil 60 Is more preferable.

  A commercially available thing can also be used for a nonionic surfactant. A nonionic surfactant may be used individually by 1 type, or may be used in combination of 2 or more type.

  The content of the nonionic surfactant in the ophthalmic composition according to the present embodiment is not particularly limited, and the type of nonionic surfactant, the type and content of other compounding components, the use and formulation form of the ophthalmic composition It sets suitably according to etc. The content of the nonionic surfactant is, for example, from the viewpoint of more prominently achieving the effects of the present invention, for example, based on the total amount of the ophthalmic composition, the total content of the nonionic surfactant is 0.00001 to 10 w. / V% is preferable, 0.0001 to 8 w / v% is more preferable, 0.001 to 5 w / v% is further preferable, and 0.01 to 4 w / v% is preferable. Is more preferably 0.01-3 w / v%, particularly preferably 0.01-2 w / v%, more preferably 0.01-1.5 w / v%. More particularly preferred is 0.01 to 0.8 w / v%, particularly preferred is 0.01 to 0.6 w / v%, and even more preferred is 0.01 to 0.5 w / v%. Most preferably it is.

  The ophthalmic composition according to this embodiment further includes vitamins (excluding retinols), antioxidants, oils, preservatives (excluding parabens), polysaccharides, vinyl compounds, amino acids, and polyvalents. You may contain 1 or more types of components selected from the group which consists of alcohol. These components are not particularly limited as long as they are pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable.

  Vitamins can be appropriately selected from known vitamins. Specific examples of vitamins include, for example, vitamin Es (d-α-tocopherol, dl-α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol, etc.) and derivatives thereof, and fats such as salts thereof Soluble vitamins, as well as vitamin B1, vitamin B2 (flavin adenine dinucleotide), niacin (nicotinic acid and nicotinic acid amide), pantothenic acid, panthenol, vitamin B6 (pyridoxine, pyridoxal and pyridoxamine), biotin, folic acid and vitamin B12 (cyanocobalamin) Water-soluble vitamins such as hydroxocobalamin, methylcobalamin and adenosylcobalamin) and salts thereof. Specific examples of vitamin salts include flavin adenine dinucleotide sodium, pyridoxine hydrochloride, calcium pantothenate, sodium pantothenate and the like. Specific examples of vitamin derivatives include, for example, tocopherol acetate.

  As vitamins, cyanocobalamin, flavin adenine dinucleotide, panthenol, pyridoxine, vitamin Es and derivatives thereof, and salts thereof are preferable, and cyanocobalamin, flavin adenine dinucleotide sodium, panthenol, pyridoxine hydrochloride and tocopherol acetate are more preferable. .

  A commercially available vitamin can also be used. A vitamin may be used individually by 1 type or may be used in combination of 2 or more type.

  Antioxidants are compounds that inhibit harmful reactions involving oxygen, and salts thereof. As the antioxidant, a known antioxidant can be appropriately selected and used.

  Specific examples of the antioxidant include butylhydroxyanisole, dibutylhydroxytoluene, ascorbic acid and salts thereof.

  As the antioxidant, butylhydroxyanisole, dibutylhydroxytoluene, and salts thereof are preferable, and butylhydroxyanisole and dibutylhydroxytoluene are more preferable.

  A commercially available thing can also be used for an antioxidant. An antioxidant may be used individually by 1 type, or may be used in combination of 2 or more type.

  Oils include plant-derived vegetable oils, animal-derived animal oils, and natural or synthetic mineral oils. As the oil, a known oil can be appropriately selected and used.

  Specific examples of the oil component include, for example, soybean oil, rice oil, rapeseed oil, cottonseed oil, sesame oil, safflower oil, almond oil, castor oil, olive oil, cacao oil, coconut oil, sunflower oil, palm oil, flax oil, perilla oil, Vegetable oils such as shea oil, coconut oil, jojoba oil, grape seed oil, and avocado oil, beeswax, lanolin (refined lanolin, etc.), orange raffie oil, animal oils such as squalane and horse oil, and petrolatum (white petrolatum and yellow petrolatum, etc.) ) And mineral oils such as liquid paraffin.

  As the oil, sesame oil, castor oil, beeswax, lanolin, petrolatum and liquid paraffin are preferable.

  A commercially available oil can also be used. The oil component may be used alone or in combination of two or more.

  The preservative is a compound having a bactericidal action or a bacteriostatic action, and a salt thereof. The preservative can be appropriately selected from known antiseptics or antibacterial agents.

  Specific examples of the preservative include, for example, quaternary ammonium compounds (benzalkonium, benzethonium, chlorhexidine, alexidine, polyhexanide), alkylpolyaminoethylglycine, benzoic acid, chlorobutanol, sorbic acid, dehydroacetic acid, oxyquinoline, phenyl Examples include ethyl alcohol, benzyl alcohol, polyquaterniums, glowkill (trade name, manufactured by Rhodia), zinc, sulfisoxazole, sulfisomidine and sulfamethoxazole, and salts thereof.

  Specific examples of the preservative salt include, for example, benzalkonium chloride, benzethonium chloride, chlorhexidine gluconate, alkyldiaminoethylglycine hydrochloride, sodium benzoate, potassium sorbate, sodium dehydroacetate, oxyquinoline sulfate, polyhexanide hydrochloride, chloride Polydronium, zinc chloride, sulfisomidine sodium and sulfamethoxazole sodium.

  As preservatives, quaternary ammonium compounds, alkylpolyaminoethylglycine, chlorobutanol, sorbic acid, phenylethyl alcohol and zinc are preferred, benzalkonium chloride, polyhexamethylene biguanide, chlorhexidine gluconate, potassium sorbate, alexidine, More preferred are polyhexanide hydrochloride, chlorobutanol, potassium sorbate, phenylethyl alcohol and zinc chloride.

  A commercially available preservative can also be used. A preservative may be used individually by 1 type, or may be used in combination of 2 or more type.

  The polysaccharide includes dextran, acidic polysaccharide, cellulosic polymer compound, and salts thereof. The polysaccharide can be appropriately selected from known polysaccharides.

  Specific examples of dextran include dextran 40 and dextran 70.

  An acidic polysaccharide is a polysaccharide having an acidic group. Specific examples of acidic polysaccharides include acidic mucopolysaccharides such as hyaluronic acid, chondroitin sulfate, chitosan, heparin, heparan, alginic acid, and derivatives thereof (for example, acetylated products), xanthan gum and gellan gum.

  As the cellulose-based polymer compound, cellulose and a polymer compound in which a hydroxyl group of cellulose is substituted with another functional group can be used. Examples of the functional group that substitutes the hydroxyl group of cellulose include a methoxy group, an ethoxy group, a hydroxymethoxy group, a hydroxyethoxy group, a hydroxypropoxy group, a carboxymethoxy group, and a carboxyethoxy group. Specific examples of the cellulose-based polymer compound include, for example, methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose (hypromellose), carboxymethyl cellulose, and carboxyethyl cellulose.

  As the polysaccharide, dextran, acidic polysaccharide, cellulose polymer compound and salts thereof are preferable, dextran, acidic polysaccharide, hydroxyethylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose and salts thereof are more preferable, and dextran, acidic mucosa. More preferred are polysaccharides, xanthan gum, gellan gum, hydroxyethylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose and salts thereof, dextran, chondroitin sulfate, hyaluronic acid, xanthan gum, gellan gum, hydroxyethylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose and salts thereof. Particularly preferred.

  A commercially available polysaccharide can also be used. A polysaccharide may be used individually by 1 type or may be used in combination of 2 or more type.

  The vinyl compound includes a vinyl polymer compound and a salt thereof. The vinyl compound can be appropriately selected from known vinyl compounds.

  Specific examples of the vinyl compound include a vinyl alcohol polymer such as polyvinyl alcohol (completely or partially saponified product), a vinyl pyrrolidone polymer such as polyvinyl pyrrolidone and a carboxyvinyl polymer, and salts thereof.

  As the vinyl compound, polyvinyl alcohol, polyvinyl pyrrolidone, carboxyvinyl polymer and salts thereof are preferable, polyvinyl alcohol, polyvinyl pyrrolidone, carboxyvinyl polymer and salts thereof are more preferable, polyvinyl alcohol, polyvinyl pyrrolidone K17, polyvinyl pyrrolidone K25, polyvinyl pyrrolidone. K30, polyvinylpyrrolidone K90, carboxyvinyl polymer and salts thereof are more preferable, and polyvinyl alcohol, polyvinylpyrrolidone K30, polyvinylpyrrolidone K90, carboxyvinyl polymer and salts thereof are particularly preferable.

  A commercially available vinyl compound can also be used. A vinyl compound may be used individually by 1 type, or may be used in combination of 2 or more type.

  Amino acids are compounds having an amino group and a carboxyl group in the molecule, derivatives thereof, and salts thereof. Amino acids can be appropriately selected from known amino acids and used.

  Examples of amino acids include amino acids and salts thereof, and amino acid derivatives and salts thereof. Specific examples of amino acids and salts thereof include, for example, monoamino monocarboxylic acids such as glycine, alanine, aminobutyric acid and aminovaleric acid, monoaminodicarboxylic acids such as aspartic acid and glutamic acid, diamino such as arginine and lysine. Examples thereof include monocarboxylic acids and salts thereof. Specific examples of amino acid derivatives and salts thereof include amino acid derivatives such as aminoethylsulfonic acid (taurine) and salts thereof. Amino acids may be any of D-form, L-form, and DL-form.

  As amino acids, monoaminodicarboxylic acid, amino acid derivatives, and salts thereof are preferable, glycine, aspartic acid, glutamic acid, arginine, taurine and salts thereof are more preferable, glycine, potassium aspartate, magnesium aspartate, sodium glutamate Arginine and taurine are more preferred.

  Commercially available amino acids can also be used. Amino acids may be used alone or in combination of two or more.

  The polyhydric alcohol is an alcohol having two or more hydroxyl groups in the molecule and a salt thereof. The polyhydric alcohol can be appropriately selected from known polyhydric alcohols.

  Examples of the polyhydric alcohol include aliphatic polyhydric alcohols such as glycerin, propylene glycol, ethylene glycol, diethylene glycol, and polyethylene glycol (300, 400, 4000, 6000) (aliphatic alcohol having two or more hydroxyl groups in the molecule). ), Sugar alcohols such as glucose, lactose, maltose, fructose, sorbitol, maltitol, mannitol, xylitol, and trehalose, and salts thereof.

  As the polyhydric alcohol, aliphatic polyhydric alcohol and sugar alcohol are preferable, and glycerin, propylene glycol, polyethylene glycol, sorbitol and mannitol are more preferable.

  The pH of the ophthalmic composition according to the present embodiment is not particularly limited as long as it is within a pharmaceutically, pharmacologically (pharmaceutical) or physiologically acceptable range. As pH of the ophthalmic composition which concerns on this embodiment, it may be 4.0-9.5, for example, it is preferable that it is 4.0-9.0, and it is 4.5-9.0. Is more preferable, it is still more preferable that it is 4.5-8.5, and it is still more preferable that it is 5.0-8.5.

  The ophthalmic composition which concerns on this embodiment can be adjusted to the osmotic pressure ratio in the range accept | permitted by a biological body as needed. An appropriate osmotic pressure ratio can be appropriately set according to the use, formulation form, method of use, etc. of the ophthalmic composition, and can be set to, for example, 0.4 to 5.0, and 0.6 to 3.0. Preferably, it is 0.8 to 2.2, more preferably 0.8 to 2.0. 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). The standard solution for measuring the osmotic pressure ratio (0.9 w / v% sodium chloride aqueous solution) was dried in sodium chloride (Japanese Pharmacopoeia standard reagent) at 500 to 650 ° C. for 40 to 50 minutes, and then in a desiccator (silica gel). The solution is allowed to cool and 0.900 g is accurately weighed 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) can be used.

  The viscosity of the ophthalmic composition according to the present embodiment is not particularly limited as long as it is within a pharmaceutically, pharmacologically (pharmaceutical) or physiologically acceptable range. As the viscosity of the ophthalmic composition according to the present embodiment, for example, the viscosity at 20 ° C. measured with a rotational viscometer (RE550 viscometer, manufactured by Toyo Sangyo Co., Ltd., rotor: 1 ° 34 ′ × R24) is 0.01 to It is preferably 10,000 mPa · s, more preferably 0.05 to 8000 mPa · s, and still more preferably 0.1 to 1000 mPa · s.

  The ophthalmic composition according to the present embodiment contains an appropriate amount of a combination of components selected from various pharmacologically active components and physiologically active components in addition to the above components, as long as the effects of the present invention are not impaired. Also good. The said component is not specifically limited, For example, the active ingredient in the ophthalmic medicine described in the over-the-counter medicine manufacture sale approval standard 2012 version (supervised by General Society of Regulatory Science) can be illustrated. Specific examples of components used in ophthalmic drugs include the following components.

Antihistamines: for example, iproheptin, diphenhydramine hydrochloride, chlorpheniramine maleate, ketotifen fumarate, olopatadine hydrochloride, levocabastine hydrochloride, etc.
Antiallergic agents: for example, sodium cromoglycate, tranilast, pemirolast potassium, acitazanolast and the like.
Steroid agents: For example, fluticasone propionate, fluticasone furancarboxylate, mometasone furancarboxylate, beclomethasone propionate, flunisolide and the like.
Anti-inflammatory agents: for example, glycyrrhetinic acid, dipotassium glycyrrhizinate, pranoprofen, methyl salicylate, glycol salicylate, allantoin, tranexamic acid, berberine, sodium azulenesulfonate, lysozyme chloride, zinc sulfate, zinc lactate, licorice, etc.
Decongestant: Tetrahydrozoline hydrochloride, tetrahydrozoline nitrate, naphazoline hydrochloride, naphazoline nitrate, epinephrine, epinephrine hydrochloride, ephedrine, phenylephrine hydrochloride, dl-methylephedrine hydrochloride, and the like.
Eye muscle modulating agent: for example, cholinesterase inhibitor having an active center similar to acetylcholine, specifically, neostigmine methyl sulfate, tropicamide, helenien, atropine sulfate, etc.
Astringent: For example, zinc white, zinc lactate, zinc sulfate and the like.
Local anesthetics: for example, lidocaine, procaine, etc.
Other: rebamipide.

In the ophthalmic composition according to the present embodiment, various additives are appropriately selected according to conventional methods according to the use and the form of the formulation, as long as the effects of the present invention are not impaired. May be used in an appropriate amount. Examples of such additives include various additives described in Pharmaceutical Additives Encyclopedia 2007 (edited by Japan Pharmaceutical Additives Association).
Typical additives include the following additives.
Carrier: An aqueous solvent such as water or hydrous ethanol.
Chelating agent: for example, ethylenediaminediacetic acid (EDDA), ethylenediaminetriacetic acid, ethylenediaminetetraacetic acid (EDTA), N- (2-hydroxyethyl) ethylenediaminetriacetic acid (HEDTA), diethylenetriaminepentaacetic acid (DTPA) and the like.
Base: for example, octyldodecanol, titanium oxide, potassium bromide, plastibase and the like.
pH adjuster: hydrochloric acid, acetic acid, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, triethanolamine, diisopropanolamine and the like.
Stabilizers: sodium formaldehyde sulfoxylate (Longalite), sodium bisulfite, sodium pyrosulfite, aluminum monostearate, glyceryl monostearate, cyclodextrin, monoethanolamine and the like.
Anionic surfactant: polyoxyethylene alkyl ether phosphate, polyoxyethylene alkyl ether sulfate, alkylbenzene sulfonate, alkyl sulfate, N-acyl taurate, and the like.
Amphoteric surfactant: lauryldimethylaminoacetic acid betaine and the like.

  When the ophthalmic composition according to the present embodiment contains water, the content of water is, for example, from the viewpoint of more prominently achieving the effect of the present invention, for example, based on the total amount of the ophthalmic composition, 80 w / v% or more and less than 100 w / v%, more preferably 85 w / v% or more and 99.5 w / v% or less, and 90 w / v% or more and 99.2 w / v% or less. More preferably.

  The water used in the ophthalmic composition according to this embodiment may be any pharmaceutical, pharmacological (pharmaceutical) or physiologically acceptable. Examples of such water include distilled water, normal water, purified water, sterilized purified water, water for injection, and distilled water for injection. These definitions are based on the 16th revised Japanese Pharmacopoeia.

  The ophthalmic composition according to the present embodiment can be prepared by adding and mixing a desired amount of the component (A) and, if necessary, other components to a desired concentration. For example, these components can be dissolved or dispersed with purified water, adjusted to a predetermined pH and osmotic pressure, and sterilized by filtration sterilization or the like.

  The ophthalmic composition according to the present embodiment can take various preparation forms depending on the purpose. Examples of the dosage form include solutions, gels, semi-solid agents (such as ointments) and the like.

  The ophthalmic composition according to the present embodiment includes, for example, eye drops (also referred to as eye drops or eye drops. Eye drops include eye drops that can be applied while wearing contact lenses), artificial tears, and eye wash. (It is also called eyewash or eyewash. In addition, eyewash includes eyewash that can be washed while wearing contact lenses.) Contact lens composition [Contact lens mounting liquid, contact lens care composition (contact lens) Disinfectant, contact lens preservative, contact lens cleaning agent, contact lens cleaning preservative) and the like. The “contact lens” includes hard contact lenses and soft contact lenses (including both ionic and non-ionic, including both silicone hydrogel contact lenses and non-silicone hydrogel contact lenses).

  When the ophthalmic composition according to the present embodiment is an ophthalmic solution, its usage / dose is not particularly limited as long as it is effective and has few side effects. For example, adults (15 years old and over) and 7 years old In the case of the above-mentioned children, a method of instilling 1 to 2 drops once, 4 times a day, a method of applying 2 to 3 drops once, 5 to 6 times a day can be exemplified.

<Container>
The ophthalmic composition according to the present embodiment is a container in which a part or all of the portion in contact with the ophthalmic composition contains a resin containing cyclic olefins (also simply referred to as “cyclic olefins-containing resin”). Accommodated and provided.

  Examples of the cyclic olefin-containing resin include a resin containing a cyclic olefin polymer (also simply referred to as “COP-containing resin”) and a resin containing a cyclic olefin copolymer (also simply referred to as “COC-containing resin”). Can be mentioned. The cyclic olefins-containing resin is preferably a COC-containing resin from the viewpoint of achieving the effects of the present invention more remarkably.

  The COP-containing resin is not particularly limited as long as it contains a polymer obtained by copolymerizing one kind of cyclic olefin, a polymer obtained by copolymerization of two or more kinds of cyclic olefins, or a hydrogenated product thereof. The COP-containing resin preferably contains a cyclic olefin ring-opening polymer or a hydrogenated product thereof. Further, the COP-containing resin preferably contains an amorphous polymer.

  The COC-containing resin is not particularly limited as long as it contains a polymer obtained by copolymerizing a cyclic olefin and an acyclic olefin, or a hydrogenated product thereof.

  Examples of the cyclic olefin include a monocyclic or polycyclic cycloalkane having a vinyl group, a monocyclic or polycyclic cycloalkene, and derivatives thereof. Preferred cyclic olefins are norbornene, tetracyclododecene, and derivatives thereof. Examples of the acyclic olefin include α-olefins such as ethylene, propylene, 1-butene, 1-pentene and 1-hexene.

  The COP-containing resin is preferably a resin containing a polymer of a cyclic olefin having a norbornene skeleton or a hydrogenated product thereof from the viewpoint of more prominently achieving the effects of the present invention. As the COC-containing resin, a resin containing a polymer obtained by copolymerizing norbornene and ethylene is preferable from the viewpoint of more prominently achieving the effects of the present invention. In addition, the polymer which copolymerized cyclic olefin and acyclic olefin may contain the other monomer as a structural component of the said polymer.

  Examples of the cyclic olefin-containing resin include polyethylene (PE; high density polyethylene (HDPE), low density polyethylene (LDPE), linear low density polyethylene (LLDPE)), polypropylene (PP), polycarbonate, (meta ) Other polymers such as acrylic polymer, polystyrene (PS), polyethylene naphthalate (PEN), polyethylene terephthalate (PET), and polyarylate may be included. From the viewpoint of more prominently achieving the effects of the present invention, the cyclic olefin-containing resin preferably further contains polyethylene (PE) and / or polypropylene (PP). When the cyclic olefins-containing resin contains polyethylene (PE) and / or polypropylene (PP), the content of polyethylene (PE) and / or polypropylene (PP) is 0 based on the total amount of cyclic olefins-containing resin. 0.001 to 50% by mass is preferable, 0.01 to 45% by mass is more preferable, 0.05 to 40% by mass is further preferable, and 0.1 to 35% by mass is preferable. Is more preferably 0.5 to 30% by mass, particularly preferably 1 to 25% by mass, still more preferably 2 to 20% by mass, and further preferably 5 to 15% by mass. Most preferably. Moreover, when cyclic olefins containing resin contains polyethylene (PE) and / or polypropylene (PP), content of polyethylene (PE) and / or polypropylene (PP) is 10 mass on the basis of the mass of the whole container. % Or more, more preferably 15% by weight or more, still more preferably 20% by weight or more, still more preferably 25% by weight or more, and more preferably 30% by weight or more. Particularly preferably, it is more preferably 35% by mass or more, still more preferably 38% by mass or more, and most preferably 40% by mass or more. Moreover, when cyclic olefins containing resin contains polyethylene (PE) and / or polypropylene (PP), content of polyethylene (PE) and / or polypropylene (PP) is 95 mass on the basis of the mass of the whole container. % Or less, more preferably 90% by mass or less, still more preferably 85% by mass or less, still more preferably 80% by mass or less, and 75% by mass or less. Particularly preferably, it is more preferably 70% by mass or less, still more preferably 65% by mass or less, and most preferably 60% by mass or less.

  In the cyclic olefins-containing resin according to this embodiment, the content of a polymer obtained by copolymerizing a cyclic olefin and an acyclic olefin is 55 to 98% by mass based on the total amount of the cyclic olefins-containing resin. Preferably, it is 60 to 98% by mass, more preferably 65 to 98% by mass, still more preferably 70 to 98% by mass, and particularly preferably 75 to 98% by mass. 80 to 98 mass% is more preferable, 85 to 98 mass% is still more preferable, and 90 to 95 mass% is most preferable. In addition, the cyclic olefin-containing resin according to the present embodiment preferably has a content of a polymer obtained by copolymerizing a cyclic olefin and an acyclic olefin of 10% by mass or more based on the mass of the entire container, It is more preferably 15% by mass or more, further preferably 20% by mass or more, still more preferably 25% by mass or more, particularly preferably 30% by mass or more, and 35% by mass or more. More preferably, it is more preferably 40% by mass or more, and most preferably 45% by mass or more. In addition, the cyclic olefin-containing resin according to the present embodiment preferably has a content of a polymer obtained by copolymerizing a cyclic olefin and an acyclic olefin of 95% by mass or less based on the mass of the entire container, It is more preferably 90% by mass or less, further preferably 85% by mass or less, still more preferably 80% by mass or less, particularly preferably 75% by mass or less, and 70% by mass or less. More preferably, it is more preferably 65% by mass or less, and most preferably 60% by mass or less.

  The cyclic olefins-containing resin may contain additives such as stabilizers and modifiers. Further, the cyclic olefin copolymer-containing resin may be reinforced with a reinforcing agent such as glass fiber.

  As the cyclic olefins-containing resin, commercially available resins can be used without particular limitation. Examples of commercially available COP-containing resins include ZEONEX (registered trademark) (manufactured by ZEON Corporation) and ZEONOR (registered trademark) (manufactured by ZEON Corporation). Examples of commercially available COC-containing resins include TOPAS (registered trademark) (manufactured by Polyplastics) and Apel (registered trademark) (manufactured by Mitsui Chemicals, Inc.).

  The type of the cyclic olefins-containing resin container may be a container generally used in the ophthalmic field. Specifically, for example, an eye drop container, an eyewash container, a contact lens mounting liquid container, a contact lens It may be a care liquid container (including a contact lens cleaning liquid container, a contact lens storage liquid container, a contact lens disinfectant container, a contact lens multipurpose solution container, etc.). The type of the cyclic olefin-containing resin container is preferably an eye drop container, a contact lens mounting liquid storage container, or a contact lens care liquid storage container. The “contact lens” includes hard contact lenses and soft contact lenses (including both ionic and non-ionic, including both silicone hydrogel contact lenses and non-silicone hydrogel contact lenses). Examples of the portion in contact with the ophthalmic composition in these containers include an inner stopper, a holed inner stopper, and an inner surface of the container (innermost layer in the case where the container has a structure composed of a plurality of layers).

  In the cyclic olefins-containing resin container according to the present embodiment, part or all of the portion in contact with the ophthalmic composition is formed of the cyclic olefins-containing resin. For example, in the case where the cyclic olefin-containing resin container has a holed stopper (nozzle), only the holed stopper may be formed of a cyclic olefins-containing resin, and the receiving part other than the holed stopper Etc. may be formed with cyclic olefins containing resin, and the whole container may be formed with cyclic olefins containing resin.

  The cyclic olefins-containing resin container may be a part of the portion in contact with the ophthalmic composition as long as it is formed of the cyclic olefins-containing resin. It is preferable that all of the contacting portions are formed of a cyclic olefin-containing resin. When a part of the container is formed of a cyclic olefins-containing resin, the type of resin forming the other part is not particularly limited. For example, polyethylene terephthalate (PET), polystyrene (PS), acrylonitrile butadiene styrene ( One or more polymers selected from the group consisting of ABS), polycarbonate, polyethylene (PE), polypropylene (PP), polymethyl methacrylate, ethylene vinyl acetate copolymer and ethylene vinyl alcohol copolymer are included as constituent components. It may be.

  The shape and capacity of the cyclic olefin-containing resin container are not particularly limited, and may be set as appropriate according to the application. In addition, the cyclic olefin-containing resin container may be a container in which a composition of a large number of times (for example, 25 times or more) is contained, and a small number of times (for example, 2 times or more and less than 25 times) It may be a container in which an amount of the composition is stored, or a container in which a single use amount of the composition is stored.

  In the case where the cyclic olefin-containing resin container is a container for storing eye drops or contact lens mounting liquid, for example, the capacity may be 0.01 mL or more and 50 mL or less, and preferably 0.05 mL or more and 40 mL or less. More preferably, it is 1 mL or more and 25 mL or less. When the cyclic olefins-containing resin container is a container that contains an eye drop or a contact lens mounting solution, and the number of times of use is a small number of times (for example, 2 times or more and less than 25 times) or a single container, The volume may be from 0.01 mL to 7 mL, preferably from 0.05 mL to 6 mL, more preferably from 0.1 mL to 5 mL, still more preferably from 0.1 mL to 3 mL. More preferably, it is 0.2 mL or more and 2 mL or less, and particularly preferably 0.2 mL or more and 1 mL or less. In addition, when the cyclic olefin-containing resin container is a container for storing an eyewash or a contact lens care liquid, for example, the capacity may be 40 mL or more and 600 mL or less, and preferably 45 mL or more and 550 mL or less. When the cyclic olefins-containing resin container is a container for storing an eyewash or a contact lens care solution, the number of times of use is a small number (for example, 2 times to less than 25 times) or a single container. The capacity may be 10 mL or more and 150 mL or less, and preferably 10 mL or more and 130 mL or less.

  The cyclic olefins-containing resin container may be a container in which the composition container and the spout are integrally formed, or may be a container having a perforated plug. The cyclic olefins-containing resin container is a container for storing an eye drop or a contact lens mounting solution, and is used a few times (for example, 2 times or more and less than 25 times) or a single container, and has a capacity of 0. When it is 1 mL or more and 3 mL or less, it is preferable that the container is a container in which the composition container and the spout are integrally formed.

  The cyclic olefins-containing resin container is preferably a transparent container from the viewpoint that foreign matter confirmation, residual amount confirmation, etc. can be observed with the naked eye. The cyclic olefin-containing resin container may be colorless or colored as long as it has transparency. The cyclic olefins-containing resin container may be a container having transparency in which internal visibility is ensured to the extent that the inside can be observed with the naked eye, and if the above internal visibility is ensured in a part of the container, The entire surface of the container is not necessarily required to have uniform transparency. As the transparency, for example, the maximum value of the light transmittance in the visible light region with a wavelength of 400 to 700 nm of the cyclic olefin-containing resin container (hereinafter also referred to as “maximum light transmittance”) may be 50% or more. 60% or more, more preferably 70% or more, and still more preferably 80% or more. The maximum light transmittance can be obtained from each light transmittance obtained by measuring the light transmittance every 10 nm between wavelengths of 400 to 700 nm using a microplate reader or the like. In addition, when the inner plug portion is formed of a cyclic olefin-containing resin and the maximum light transmittance cannot be measured from the shape, size, etc., the transparency by visual observation is similar. The maximum light transmittance of the commercially available cyclic olefins-containing resin can be obtained to make the inner plug transparent. Moreover, the transparency of the inner plug can also be confirmed by carrying out an insoluble foreign substance inspection method prescribed by the Japanese Pharmacopoeia.

  The thickness of the cyclic olefins-containing resin container may be 0.01 to 3.0 mm, preferably 0.05 to 2.0 mm, from the viewpoint of more prominently achieving the effect of improving liquid breakage. It is more preferably 0.1 to 1.5 mm, further preferably 0.1 to 1.2 mm, still more preferably 0.1 to 1.0 mm, and 0.1 to 0.8 mm. Is particularly preferably 0.1 to 0.6 mm, more particularly preferably 0.1 to 0.5 mm, and most preferably 0.1 to 0.4 mm. .

  The drop amount per drop of the ophthalmic composition according to the present embodiment is preferably designed to be 1 to 99 μL, and more preferably 1 to 79 μL, from the viewpoint that the effects of the present invention are more remarkably exhibited. More preferably, it is more preferably 7 to 79 μL, and still more preferably 13 to 79 μL.

  In the ophthalmic composition according to the present embodiment, the volume of the ophthalmic composition, the dripping amount per drop, the size of the container, the shape of the inner plug, the shape of the spout so that the number of times of use is small or single. Etc. can be designed as appropriate.

  The ophthalmic composition according to the present embodiment can also be provided as an ophthalmic composition containing a cyclic olefin-containing resin container. The present invention can also be regarded as an ophthalmic product (eye drops, eye wash, contact lens-related product, etc.) in which the ophthalmic composition of the present invention is contained in a cyclic olefins-containing resin container.

[2. Suppression of wetting of cyclic olefin-containing resins
In the ophthalmic composition according to this embodiment, wetting of the resin containing cyclic olefins is suppressed. Therefore, as one embodiment of the present invention, the ophthalmic composition includes (A) one or more selected from the group consisting of terpenoids, retinols, and parabens, and the ophthalmic composition includes cyclic olefins. There is provided a method of imparting a wetting suppression effect to a resin containing selenium. In another embodiment of the present invention, the ophthalmic composition comprises (A) one or more selected from the group consisting of terpenoids, retinols, and parabens, and the ophthalmic composition includes a cyclic olefin. Provided is a method for suppressing wetting of a resin containing a kind.

  In addition, about the formulation form of an ophthalmic composition, a use, etc., such as the kind and content of other components, such as the kind and content of the component (A) in this embodiment, [1. As described in [Ophthalmic composition].

[3. Suppression of odor change
When the ophthalmic composition contained in a container formed of a resin containing a cyclic olefin according to the present embodiment further contains the component (B), the fragrance is maintained or the odor is suppressed. The change of odor is suppressed. Therefore, as one embodiment of the present invention, the ophthalmic composition housed in a container formed of a resin containing cyclic olefins is selected from the group consisting of (A) terpenoids, retinols, and parabens. There is provided a method of imparting an odor change inhibiting action to the ophthalmic composition, comprising blending a seed or more and (B) a buffer. In another embodiment of the present invention, the ophthalmic composition contained in a container formed of a resin containing cyclic olefins is selected from the group consisting of (A) terpenoids, retinols, and parabens. There is provided a method for suppressing a change in odor of the ophthalmic composition, comprising blending one or more types and (B) a buffering agent.

  In addition, about the formulation form of a ophthalmic composition, a use, etc., such as the kind and content of other components, such as the kind and content of (A) component and (B) component in this embodiment, [1. As described in [Ophthalmic composition].

  Moreover, as one embodiment of the present invention, there is provided a method of using an ophthalmic composition, wherein the ophthalmic composition contains (A) one or more selected from the group consisting of terpenoids, retinols, and parabens, and Provided is a method of use characterized by being contained in a container formed of a resin containing cyclic olefins and having a small number of uses or a single use. In particular, in the case of a small number of times or a single use, in order to exert a desired pharmacological effect, there is a demand for suppression of liquid residue and improvement of liquid drainage. In this embodiment, (A) terpenoids and retinols And the ophthalmic composition containing at least one selected from the group consisting of parabens is contained in a container formed of a resin containing cyclic olefins, so that the liquid residue is suppressed and the liquid runs out. The effect of improving is produced.

  Hereinafter, the present invention will be specifically described based on test examples, but the present invention is not limited thereto.

[Test method: Measurement method of dynamic contact angle (advance angle)]
Using a contact angle meter DM-501 (manufactured by Kyowa Interface Science Co., Ltd.), the dynamic contact angle (advance angle) of each test solution was measured according to the measurement procedure of the expansion / contraction method of the contact angle meter. The dynamic contact angle (advance angle) is a contact angle when the solid / liquid interface moves.

  Specifically, each 0.2 mm-thick sheet material (low density polyethylene (LDPE), linear low density polyethylene (LLDPE), polypropylene (PP), cyclic olefin copolymer (COC; TOPAS 8007 (polyplastic) S))) or a resin containing two or more of these) was placed on the stage of a contact angle meter, and the test solution was set in a dispenser. At room temperature, 1 μL of a test liquid droplet was dropped on each vessel material to form a hemisphere. Next, the tip of the liquid discharge part of the dispenser was immediately applied to the upper part of the hemisphere. In this state, the test solution was continuously discharged at a discharge speed of 6 μL / second, and the shape of the droplet was photographed 15 times from the side surface every 0.1 second. In order to match the measurement conditions, the test solutions to be paired when calculating the change rate of the dynamic contact angle were continuously measured under the same temperature conditions (room temperature) using the same container material.

  Next, using the contact angle meter analysis software FAMAS, the left and right contact angles were determined for each image. Here, the contact angle refers to the surface of each sheet-like container material having a thickness of 0.2 mm, the tangent drawn from the contact point P of the test solution and air to the test solution, and the tangent drawn to the surface of each sheet-like container material. Means the corner on the side containing the test solution. There are two contact points P on the left and right of each droplet. As the droplets expanded as the test liquid was ejected, the contact angle changed and then behaved almost constant. Therefore, when the average value of the left and right contact angles is calculated for each image, and five consecutive values are selected by arranging the average values in the order in which the images were taken, the standard deviation of the five average values is first 2. The first average value (the average value of the left and right contact angles in the image captured first among the five average values) when the angle was 0 ° or less was taken as the measurement value of the dynamic contact angle in the same measurement. For all the test solutions, no standard deviation greater than 2.0 ° was observed after the standard deviation first became 2.0 ° or less. Even when the contact angle did not change during the process of expanding the droplet, the measured value of the dynamic contact angle was obtained according to the above criteria.

  The above operation was repeated three times for each test solution, and the average value of the three measured values obtained was taken as the dynamic contact angle of the test solution. The standard deviation of the three measurements was 2.0 ° or less for all test solutions.

[Test Example 1: Evaluation of dynamic contact angle (advance angle) (1)]
Test solutions of each test example shown in Tables 1 to 3 were prepared by a conventional method. The unit of each component in Tables 1 to 3 is w / v%.

According to the procedure shown in the above test method, the dynamic contact angle of each test solution was determined (average value of three measured values). Subsequently, the change rate of the dynamic contact angle of the test liquid of the test example with respect to the corresponding prescription liquid was calculated by the following [Formula 1]. The calculated results are shown in Tables 1 to 3.
[Formula 1] Change rate of dynamic contact angle (%) = {(dynamic contact angle of test liquid of test example / dynamic contact angle of corresponding prescription liquid) -1} × 100
In addition, the corresponding prescription liquid is prescription which remove | excluded (A) component from prescription of each test liquid, About Test Examples 1-3, 1-5, and 1-7, Test Example 1-1, Test Example 1 -4, 1-6, and 1-8, Test Example 1-2, Test Examples 1-11, 1-13, and 1-15, Test Example 1-9, Test Examples 1-12, 1-14, and 1 Test Example 1-10 for -16 and Test Example 1-17 for Test Examples 1-18 to 1-24.

  As shown in Tables 1 and 2, when low density polyethylene (LDPE) or polypropylene (PP) is used as the container material, the dynamic contact angle of the test solution containing the component (A) is a test not containing the component (A). It turns out that it is smaller than the dynamic contact angle of the liquid. That is, it has been clarified that the composition containing the component (A) has a problem that the dynamic contact angle with respect to a resin containing low density polyethylene (LDPE) or polypropylene (PP) is small and wet easily.

  On the other hand, as shown in Table 3, when a cyclic olefin copolymer (COC) is used as the container material, the dynamic contact angle of the test solution containing the component (A) is the dynamic contact angle of the test solution not containing the component (A). It is larger than that, and wetting of the container can be suppressed. Further, when a resin further containing low-density polyethylene (LDPE) in addition to the cyclic olefin copolymer (COC) is used as the container material, the dynamic contact angle is further increased as compared with a resin containing only the cyclic olefin copolymer (COC). It is large and can further suppress the wetting of the container. As a container material, a resin containing a cyclic olefin copolymer (COC) and polyethylene (PE) having a polyethylene (PE) content of more than 10 w / w% and 50 w / w% or less is used. Even if it was, the same effect was shown.

[Test Example 2: Evaluation of dynamic contact angle (advance angle) (2)]
Test solutions for each test example shown in Table 4 were prepared by a conventional method. The unit of each component in Table 4 is w / v%. The unit of retinol palmitate is international units / 100 mL.

According to the procedure shown in the above test method, the dynamic contact angle of each test solution was determined (average value of three measured values). Next, for Test Examples 2-1 to 2-6, the rate of change in the dynamic contact angle of the test liquid of the test example with respect to Test Example 2-1 was calculated according to [Formula 2-1] below, and Test Example 2- For 7 to 2-11, the change rate of the dynamic contact angle of the test liquid of the test example with respect to test example 2-7 was calculated by the following [Formula 2-2]. The calculated results are shown in Table 4.
[Formula 2-1] Change rate of dynamic contact angle (%) = {(dynamic contact angle of test liquid of test example / dynamic contact angle of test example 2-1) -1} × 100
[Formula 2-2] Change rate of dynamic contact angle (%) = {(dynamic contact angle of test liquid of test example / dynamic contact angle of test example 2-7) -1} × 100

  As shown in Table 4, when a cyclic olefin copolymer (COC) is used as the container material, the dynamic contact angle of the test solution containing the component (A) is larger than the dynamic contact angle of the test solution not containing the component (A). It is large and can suppress the wetting with respect to the container (Test Examples 2-1 to 2-6). When a resin further containing low density polyethylene (LDPE) in addition to cyclic olefin copolymer (COC) is used as the container material, the dynamic contact angle of the test solution containing component (A) contains component (A). It is larger than the dynamic contact angle of the test solution that does not, and can suppress wetting of the container (Test Examples 2-7 to 2-11). As a container material, a resin containing a cyclic olefin copolymer (COC) and polyethylene (PE) having a polyethylene (PE) content of more than 10 w / w% and 50 w / w% or less is used. Even if it was, the same effect was shown.

[Test Example 3: Evaluation of dynamic contact angle (advance angle) (3)]
Test solutions of each test example shown in Tables 5 to 7 were prepared by a conventional method. The unit of each component in Tables 5-7 is w / v%. The unit of retinol palmitate is international units / 100 mL.

According to the procedure shown in the above test method, the dynamic contact angle of each test solution was determined (average value of three measured values). Subsequently, the change rate of the dynamic contact angle of the test liquid of the test example with respect to the corresponding prescription liquid was calculated by the following [Formula 3]. The calculated results are shown in Tables 5-7.
[Formula 3] Change rate of dynamic contact angle (%) = {(dynamic contact angle of test liquid of test example / dynamic contact angle of corresponding prescription liquid) -1} × 100

  In addition, a corresponding prescription liquid is a prescription which adjusted pH by hydrochloric acid and sodium hydroxide appropriate amount except the (B) component from prescription of each test liquid (the remainder is purified water). The container material is a cyclic olefin copolymer (COC).

  As shown in Tables 5 to 7, the ophthalmic composition containing the combination of the component (B) with the component (A) has a larger dynamic contact angle than the test solution containing only the component (A). , Wetting of the container can be suppressed. The same effect can be obtained even when a resin containing cyclic olefin copolymer (COC) and polyethylene (PE) is used as the container material and the content of polyethylene (PE) is 50 w / w% or less. showed that.

[Test Example 4: Sensory evaluation (1)]
Test solutions of each test example shown in Table 8 were prepared by a conventional method, and 1 mL each was filled into a 5 mL glass ampule tube. The unit of each component in Table 8 is w / v%. Furthermore, container material pieces each having a width of 2 mm, a length of 20 mm, and a thickness of 0.2 mm were dipped one by one and quickly sealed. The container material is a cyclic olefin copolymer (COC; TOPAS 8007 (manufactured by Polyplastics)). Next, heat treatment was performed to stand still in a thermostat. The heat treatment was performed at 60 ° C. for 160 minutes in Test Examples 4-1 to 4-4, and at 60 ° C. for 80 minutes in Test Examples 4-5 to 4-8. Thereafter, 20 μL of each test solution before and after the heat treatment was dropped on the arms of four subjects who were sensitive to odors, spread with a finger in a circular shape having a diameter of about 2 cm, and smelled, and evaluated by the VAS (Visual Analog Scale) method. That is, regarding “fragrance”, “not felt at all” was 0 mm and “very felt” was 100 mm at both ends of a straight line of 100 mm, and one point on the straight line corresponding to the aroma of each test solution was shown to the subject. A distance (mm) from a point of 0 mm was measured, and an average value of four people was calculated and used as a VAS value of the test solution. Next, the VAS change value before and after the heat treatment was calculated by the following [Equation 4-1]. Then, the fragrance retention rate of the test liquid of the test example with respect to the corresponding test example was calculated by the following [Formula 4-2]. The calculated results are shown in Table 8.
[Formula 4-1] VAS change value = VAS value of test solution before heat treatment−VAS value of test solution after heat treatment [Formula 4-2] Retention rate of aromaticity (%) = {1- (for each test example VAS change value / VAS change value of corresponding test example)} × 100

  The corresponding test example is a test example in which the container material is not immersed. Test example 4-2 is test example 4-1, test example 4-4 is test example 4-3, and test example 4-6. For Test Example 4-5 and Test Example 4-8 for Test Example 4-7.

  As shown in Table 8, the test example in which the COC-containing resin container material was immersed in the test solution containing the component (A) was compared with the test example in which the COC-containing resin container material was not immersed in the test solution containing the component (A). Thus, it became clear that there is a problem that the retention rate of fragrance deteriorates.

[Test Example 5: Sensory evaluation (2)]
Test solutions of each test example shown in Tables 9 and 10 were prepared by a conventional method, and 1 mL each was filled into a 5 mL glass ampule tube. The unit of each component in Tables 9 and 10 is w / v%. Furthermore, container material pieces each having a width of 2 mm, a length of 20 mm, and a thickness of 0.2 mm were dipped one by one and quickly sealed. The container material is a cyclic olefin copolymer (COC; TOPAS 8007 (manufactured by Polyplastics)). Next, heat treatment was performed to stand still in a thermostat. The heat treatment was performed at 60 ° C. for 160 minutes in Test Examples 5-1 to 5-12, and at 60 ° C. for 80 minutes in Test Examples 5-13 to 5-24. Thereafter, 20 μL of each test solution before and after the heat treatment was dropped on the arms of four subjects who were sensitive to odors, spread with a finger in a circular shape having a diameter of about 2 cm, and smelled, and evaluated by the VAS (Visual Analog Scale) method. That is, regarding “fragrance”, “not felt at all” was 0 mm and “very felt” was 100 mm at both ends of a straight line of 100 mm, and one point on the straight line corresponding to the aroma of each test solution was shown to the subject. A distance (mm) from a point of 0 mm was measured, and an average value of four people was calculated and used as a VAS value of the test solution. Next, the VAS change value before and after the heat treatment was calculated by the following [Equation 5-1]. Then, the fragrance retention rate of the test liquid of the test example with respect to the corresponding test example was calculated by the following [Formula 5-2]. The calculated results are shown in Tables 9 and 10.
[Formula 5-1] VAS change value = VAS value of test solution before heat treatment−VAS value of test solution after heat treatment [Formula 5-2] Retention rate of aromaticity (%) = {1- (for each test example VAS change value / VAS change value of corresponding test example)} × 100

  In addition, the corresponding test example is a formulation in which the component (B) is removed from the formulation of each test solution, and the pH is adjusted with hydrochloric acid and sodium hydroxide in appropriate amounts (the balance is purified water). The container material is a cyclic olefin copolymer (COC).

  As shown in Tables 9 and 10, the scent retention was improved in the test solution containing the component (A) and the component (B) as compared to the test solution containing the component (A). The same effect can be obtained even when a resin containing cyclic olefin copolymer (COC) and polyethylene (PE) is used as the container material and the content of polyethylene (PE) is 50 w / w% or less. showed that.

[Test Example 6: Sensory evaluation (3)]
Test solutions of each test example shown in Table 11 were prepared by a conventional method, and 1 mL each was filled into a 5 mL glass ampule tube. The unit of each component in Table 11 is w / v%. The unit of retinol palmitate is international units / 100 mL. Furthermore, container material pieces each having a width of 2 mm, a length of 20 mm, and a thickness of 0.2 mm were dipped one by one and quickly sealed. The container material is a cyclic olefin copolymer (COC; TOPAS 8007 (manufactured by Polyplastics)), or a container material containing COC 60 w / w% and low-density polyethylene (LDPE) 40 w / w%. Next, heat treatment was performed in a constant temperature bath at 60 ° C. for 80 minutes. Thereafter, 20 μL of each test solution after heat treatment was dropped onto the arms of four subjects who were sensitive to odors, spread with a finger in a circular shape having a diameter of about 2 cm, smelled, and evaluated by the VAS (Visual Analog Scale) method. That is, regarding “odor”, at both ends of a straight line of 100 mm, “not felt at all” was set to 0 mm and “very felt” was set to 100 mm, and the subject was shown a point on the straight line corresponding to the odor of each test solution. A distance (mm) from a point of 0 mm was measured, and an average value of four people was calculated and used as a VAS value of the test solution. Subsequently, the improvement rate of the odor after heat processing was computed by the following [Formula 6]. The calculated results are shown in Table 11.
[Expression 6] Odor improvement rate (%) = {1− (VAS value of test example / VAS value of corresponding test solution)} × 100

  The corresponding test liquid is a test liquid that does not immerse the container material.

  As shown in Table 11, it became clear that the test example containing (A) component had the subject that an odor deteriorates after heat processing.

[Test Example 7: Sensory evaluation (4)]
Test solutions of each test example shown in Table 12 were prepared by a conventional method, and 1 mL each was filled into a 5 mL glass ampule tube. The unit of each component in Table 12 is w / v%. The unit of retinol palmitate is international units / 100 mL. Furthermore, container material pieces each having a width of 2 mm, a length of 20 mm, and a thickness of 0.2 mm were dipped one by one and quickly sealed. The container material is a cyclic olefin copolymer (COC; TOPAS 8007 (manufactured by Polyplastics)), or a container material containing COC 60 w / w% and low-density polyethylene (LDPE) 40 w / w%. Next, heat treatment was performed in a constant temperature bath at 60 ° C. for 80 minutes. Thereafter, 20 μL of each test solution after heat treatment was dropped onto the arms of four subjects who were sensitive to odors, spread with a finger in a circular shape having a diameter of about 2 cm, smelled, and evaluated by the VAS (Visual Analog Scale) method. That is, regarding “odor”, at both ends of a straight line of 100 mm, “not felt at all” was set to 0 mm and “very felt” was set to 100 mm, and the subject was shown a point on the straight line corresponding to the odor of each test solution. The distance (mm) from the point of 0 mm was measured, the average value of four people was calculated, and the VAS value of the test solution was calculated. Then, the improvement rate of odor after heat treatment was calculated by the following [Equation 7]. The calculated results are shown in Table 12.
[Expression 7] Odor improvement rate (%) = {1− (VAS value of test example / VAS value of corresponding test solution)} × 100

  The corresponding test solution is a formulation in which the component (B) is removed from the formulation of each test solution, and the pH is adjusted with appropriate amounts of hydrochloric acid and sodium hydroxide (the balance is purified water).

  As shown in Table 12, the odor improved in the test example containing the component (A) and the component (B) compared to the test example containing only the component (A). As a container material, a resin containing a cyclic olefin copolymer (COC) and polyethylene (PE) having a polyethylene (PE) content of more than 40 w / w% and 50 w / w% or less is used. Even if it was, the same effect was shown.

[Test Example 8: Evaluation of dynamic contact angle (advance angle) (4)]
Test solutions for each test example shown in Table 14 were prepared by a conventional method. The unit of each component in Table 14 is w / v%. The unit of retinol palmitate is international units / 100 mL. Further, as a container material, a resin (container material A) containing a cyclic olefin copolymer (COC; TOPAS 8007 (manufactured by Polyplastics)) shown in Table 13 and COC and low density polyethylene (LDPE) or linear low density Resin (container materials B, C, D and E) containing polyethylene (LLDPE) was used. In Table 13, the unit of each constituent component contained in the container material is w / w%.

According to the procedure shown in the above test method, the dynamic contact angle of each test solution was determined (average value of three measured values). Subsequently, the change rate of the dynamic contact angle of the test liquid of the test example with respect to the corresponding prescription liquid was calculated by the following [Formula 8]. The calculated results are shown in Table 14.
[Equation 8] Change rate of dynamic contact angle (%) = {(dynamic contact angle of test liquid in test example / dynamic contact angle in contact with container material A of corresponding prescription liquid) -1} × 100
In addition, a corresponding prescription liquid is a prescription which remove | excluded (A) component from prescription of each test liquid (the remainder is purified water). Container material A was used in determining the dynamic contact angle of the corresponding prescription solution.

  When a resin containing COC and LDPE or COC and LLDPE is used as the container material, the dynamic contact angle of the test solution containing the component (A) is larger than the dynamic contact angle of the test solution not containing the component (A). It is large and can suppress wetting to the container. In particular, the resin containing COC and LLDPE has a larger dynamic contact angle.

[Test Example 9: Evaluation of dynamic contact angle (advance angle) (5)]
Test solutions for each test example shown in Table 15 were prepared by a conventional method. The unit of each component in Table 15 is w / v%. The unit of retinol palmitate is international units / 100 mL. Moreover, the container material shown in Table 13 of Test Example 8 was used as the container material.

According to the procedure shown in the above test method, the dynamic contact angle of each test solution was determined (average value of three measured values). Subsequently, the change rate of the dynamic contact angle of the test liquid of the test example with respect to the corresponding prescription liquid was calculated by the following [Formula 9]. The calculated results are shown in Table 15.
[Formula 9] Change rate of dynamic contact angle (%) = {(dynamic contact angle of test liquid in test example / dynamic contact angle in contact with container material A of corresponding prescription liquid) -1} × 100
In addition, a corresponding prescription liquid is a prescription which adjusted pH by hydrochloric acid and sodium hydroxide appropriate amount except the (B) component from prescription of each test liquid (the remainder is purified water). Container material A was used in determining the dynamic contact angle of the corresponding prescription solution.

  When a resin containing COC and LDPE, or COC and LLDPE is used as the container material, the test solution containing the combination of component (A) and component (B) compared to the test solution containing only component (A) The dynamic contact angle is large, and wetting with respect to the container can be suppressed. In particular, the resin containing COC and LLDPE has a larger dynamic contact angle.

[Test Example 10: Sensory evaluation (5)]
(Fragrance retention)
Test solutions of test examples (Test Examples 10-1 to 10-5) shown in Table 16 were prepared by a conventional method, and 1 mL each was filled into a 5 mL glass ampule tube. The unit of each component in Table 16 is w / v%. Furthermore, container material pieces each having a width of 2 mm, a length of 20 mm, and a thickness of 0.2 mm were dipped one by one and quickly sealed. The container material shown in Table 13 of Test Example 8 was used as the container material. Next, heat treatment was performed to stand still in a thermostat. The heat treatment was performed at 60 ° C. for 160 minutes in Test Examples 10-1 to 10-3, and at 60 ° C. for 80 minutes in Test Examples 10-4 and 10-5. Thereafter, 20 μL of each test solution before and after the heat treatment was dropped on the arms of four subjects who were sensitive to odors, spread with a finger in a circular shape having a diameter of about 2 cm, and smelled, and evaluated by the VAS (Visual Analog Scale) method. That is, regarding “fragrance”, “not felt at all” was 0 mm and “very felt” was 100 mm at both ends of a straight line of 100 mm, and one point on the straight line corresponding to the aroma of each test solution was shown to the subject. A distance (mm) from a point of 0 mm was measured, and an average value of four people was calculated and used as a VAS value of the test solution. Subsequently, the VAS change value before and after the heat treatment was calculated by the following [Equation 10-1]. Then, the fragrance retention rate of the test liquid of the test example with respect to the corresponding test example was calculated by the following [Formula 10-2]. The calculated results are shown in Table 16.
[Formula 10-1] VAS change value = VAS value of test liquid before heat treatment−VAS value of test liquid after heat treatment [Formula 10-2] Aromaticity retention (%) = {1- (for each test example) VAS change value / VAS change value of corresponding test example)} × 100

  In addition, the corresponding test example is a formulation in which the component (B) is removed from the formulation of each test solution, and the pH is adjusted with hydrochloric acid and sodium hydroxide in appropriate amounts (the balance is purified water). In determining the VAS change value of the corresponding test example, the container material A was used.

(Odor improvement rate)
A test solution of Test Example 10-6 shown in Table 16 was prepared by a conventional method, and 1 mL was filled into a 5 mL glass ampule tube. The unit of each component in Table 16 is w / v%. The unit of retinol palmitate is international units / 100 mL. Furthermore, container material pieces each having a width of 2 mm, a length of 20 mm, and a thickness of 0.2 mm were dipped one by one and quickly sealed. The container material shown in Table 13 of Test Example 8 was used as the container material. Next, heat treatment was performed in a constant temperature bath at 60 ° C. for 80 minutes. Thereafter, 20 μL of the test solution after heat treatment was dropped onto the arms of four subjects who were sensitive to odors, spread with a finger in a circle of about 2 cm in diameter, and smelled, and evaluated by the VAS (Visual Analog Scale) method. That is, with respect to the “odor”, at both ends of a straight line of 100 mm, “not felt at all” was set to 0 mm and “very felt” was set to 100 mm, and the subject was shown one point on the straight line corresponding to the odor of the test solution. A distance (mm) from a point of 0 mm was measured, and an average value of four people was calculated and used as a VAS value of the test solution. Subsequently, the improvement rate of the odor after heat processing was computed by the following [Formula 10-3]. The calculated results are shown in Table 16.
[Formula 10-3] Odor improvement rate (%) = {1− (VAS value of test example / VAS value of corresponding test solution)} × 100

  The corresponding test solution is a formulation in which the component (B) is removed from the formulation of each test solution, and the pH is adjusted with appropriate amounts of hydrochloric acid and sodium hydroxide (the balance is purified water). In determining the VAS value of the corresponding test solution, the container material A was used.

  In each of Test Examples 10-1 to 10-5 using the resin containing the component (A) and the component (B) as the test liquid and containing COC and LDPE, or COC and LLDPE as the container material, the fragrance retention rate Improved. In particular, when a resin containing COC and LLDPE (container material D of Test Examples 10-1 to 10-5) was used as the container material, the fragrance retention rate was further improved.

  The odor improved in Test Example 10-6 using the resin containing the components (A) and (B) as the test liquid and the resin containing COC and LDPE, or COC and LLDPE as the container material. In particular, when a resin containing COC and LLDPE (container materials C and D of Test Example 10-6) was used as the container material, the odor was further improved.

  From the above results, the ophthalmic composition according to the present embodiment has an effect of suppressing wetting, so that liquid residue is suppressed. As a result, contamination due to contamination with bacteria and foreign matters can be suppressed, and high hygiene quality required for delicate ocular mucosal tissues can be realized. Moreover, since the ophthalmic composition which concerns on this embodiment has an effect in which wetting is suppressed, liquid running out improves. Thereby, the dispersion | variation in the dripping amount calculated | required for the use to the eye or contact lens which is a comparatively small site | part can be made small. Furthermore, since the ophthalmic composition according to the present embodiment has an effect of suppressing a change in odor, it is possible to suppress the generation of a strange odor due to contact with the container.

Claims (6)

  (A) An ophthalmic composition containing one or more selected from the group consisting of terpenoids, retinols, and parabens, wherein a part or all of the portion in contact with the ophthalmic composition contains a cyclic olefin An ophthalmic composition comprising a container formed of   The ophthalmic composition according to claim 1, wherein the resin forming the container further contains polyethylene.   The ophthalmic composition according to claim 1 or 2, further comprising (B) a buffer.   The ophthalmic composition according to any one of claims 1 to 3, wherein the water content is 80 w / v% or more and less than 100 w / v% based on the total amount of the ophthalmic composition.   The ophthalmologic according to any one of claims 1 to 4, wherein a maximum value of light transmittance in a visible light region having a wavelength of 400 to 700 nm of a container formed of a resin containing cyclic olefins is 50% or more. Composition.   The ophthalmic composition is provided with one or more selected from the group consisting of (A) terpenoids, retinols, and parabens, and the ophthalmic composition is provided with a wetting inhibitory action on a resin containing a cyclic olefin. how to.