JP2022120131A - Eye-drop type eyewash medicinal composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a composition suitable for a new eyewash technique, i.e., eyewash by eye drop (hereinafter also referred to as "eye drop-type eyewash"), and dosage and administration thereof.

SOLUTION: Provided is an eye-drop type eyewash medicinal composition having a viscosity of 12 mPa s or less. The eye-drop type eyewash medicinal composition is used so that 4 or more drops are applied once per eye.

SELECTED DRAWING: None

COPYRIGHT: (C)2022,JPO&INPIT

Description

The present invention relates to an eye-drop type eye wash medicinal composition having a viscosity of 12 mPa·s or less, wherein the eye drop type eye wash medicinal composition is used so that 4 or more drops are instilled once per eye. Regarding.

With the increase in hay fever patients and the widespread use of contact lenses, eye troubles are increasing. Also, various eye drops have been developed and used for its prevention and treatment. As a method of preventing such troubles in the eyes in advance, the use of eye washes that effectively remove stains such as pollen, dust and proteins that have entered the eyes is increasing. As for such an eye wash, after putting the eye wash in the eye wash cup, the user's eye periphery is pressed against the cup opening edge, and the eye wash in the cup is removed by turning the face upward together with the cup. It is generally of the type in which the user's eyes are brought into contact with the eye surface and the eyes are washed by blinking several times (such type of eye wash is hereinafter also referred to as "cup type eye wash").

This cup-type eye wash requires about 5 mL of eye wash for one eye wash, and the amount is large when used multiple times, so it is not excellent in portability. In addition, since a large amount of eye wash, about 5 mL, is used for one eye wash, excessive tear fluid on the surface of the eye is washed away, causing a dry feeling in the eye. Furthermore, according to the cup-type eye wash method, the eye wash medicine comes into contact with the skin around the eyes, etc., so the skin moisturizing ingredients around the eyes are washed away and the skin dries (Patent Document 1). There is also the problem that adhering dirt (sweat, pollen, dust, etc.) enters the eyes that should have been washed, causing eye troubles.

However, there is no research on an eye wash method that has an effect of removing stains (pollen, dust, protein, etc.) that is close to, equal to or greater than that of cup-type eye wash, and that solves the above-mentioned problems of cup-type eye wash. Very little has been done.

Japanese Patent Application Laid-Open No. 2002-003404

An object of the present invention is to find a composition suitable for a new eye wash method, that is, an eye wash using eye drops (hereinafter also referred to as "eye drop type eye wash") and a dosage and administration thereof.

When the present inventors use an eye-drop type eye wash, what kind of composition should be used in what dosage and amount to obtain an eye wash effect similar to, equivalent to, or greater than that of a cup-type eye wash? studied intensively. As a result, the present inventors found that when performing an eye-drop type eye wash, the viscosity of the composition and the number of drops per eye (or the total amount of eye drops per eye) and It was found that there is a large correlation between the effect of washing the eyes. More specifically, a composition having a viscosity of 12 mPa s or less is instilled once per eye, 4 drops or more, preferably 4 drops or more and 6 drops or less. It has been found that an eye wash effect equal to or greater than that can be obtained. In addition, since the eyes are washed by instillation, the contact of the eye wash with the skin and eyelashes around the eye is minimized, and the eye wash contaminated by contact with the skin and eyelashes around the eye does not enter the eye. The present invention has been completed based on the finding that eye troubles caused by exposure to water can be prevented and/or avoided. Furthermore, the present inventors also found that a composition obtained by further blending boric acid or a salt thereof and/or edetic acid or a salt thereof with the above composition has an inhibitory effect on pollen bursting.

That is, the present invention is as follows.
[1] A medicinal eye wash composition having a viscosity of 12 mPa·s or less, which is used in such a manner that 4 or more drops are instilled once per eye.
[2] The eye-drop type eye wash medicinal composition according to [1], which is used so that 6 drops or less are instilled once per eye.
[3] An eye-drop type eye wash composition having a viscosity of 12 mPa·s or less, wherein the eye drop type eye wash composition is used so that the total amount of eye drops is 120 μL or more once per eye. Composition.
[4] The eye-drop type eye wash medicinal composition according to [3], which is used in such a way that the total amount of eye drops is 300 μL or less once per eye.
[5] Any of [1] to [4], further containing at least one selected from the group consisting of antiphlogistic/astringent ingredients, antihistamine ingredients, inorganic salts, alkylpolyaminoethylglycine and boric acid or salts thereof 3. The eye drop type eyewash medicinal composition according to .
[6] The ophthalmic eye wash composition according to any one of [1] to [4], further comprising boric acid.
[7] The eye drop type eye wash composition according to any one of [1] to [6], further comprising a thickening agent.
[8] The ophthalmic eye wash composition according to any one of [1] to [7], further comprising a tonicity agent, a stabilizer, a pH adjuster and a solubilizer.
[9] The eye-drop type eye wash medicinal composition according to any one of [1] to [8], which has a pH of 6.5 or more and 7.0 or less.
[10] The eye-drop type eye wash medicinal composition according to any one of [1] to [9], which is used for washing away stains and foreign substances on the surface of the eye.
[11] The eye-drop type eye wash medicinal composition according to [10], wherein the dirt or foreign matter is pollen, eye secretions or PM2.5.
[12] Housed in an eyedropper container formed from at least one selected from polypropylene, low-density polyethylene, high-density polyethylene, polyethylene terephthalate, polybutylene terephthalate, cycloolefin polymer, and cycloolefin copolymer [1] to [11] ] The eye-drop type eye wash medicinal composition according to any one of the above.
[13] The eye-drop type eye wash composition according to [12], wherein the eye drop container is a liquid-sprayable eye drop container.

Furthermore, the present invention also relates to:
[14] An instillation-type eyewashing method, comprising instilling 4 or more drops of a composition having a viscosity of 12 mPa·s or less once per eye.
[15] The method of [14], wherein 6 drops or less are instilled once per eye.
[16] An eye-drop type eyewashing method comprising instilling a composition having a viscosity of 12 mPa·s or less once per eye in a total volume of 120 μL or more.
[17] The method according to [16], wherein the total volume of eye drops is 300 μL or less once per eye.
[18] The composition further contains at least one selected from the group consisting of antiphlogistic/astringent components, antihistamine components, inorganic salts, alkylpolyaminoethylglycine and boric acid or salts thereof, [14]-[ 17].
[19] The method according to any one of [14] to [17], wherein the composition further contains boric acid.
[20] The method according to any one of [14] to [19], wherein the composition further contains a thickening agent.
[21] The method according to any one of [14] to [20], wherein the composition further contains a tonicity agent, a stabilizer, a pH adjuster and a solubilizer.
[22] The method according to any one of [14] to [21], wherein the composition has a pH of 6.5 or more and 7.0 or less.
[23] The method according to any one of [14] to [22] for washing away stains and foreign substances on the ocular surface.
[24] The method of [23], wherein the dirt or foreign matter is pollen, ocular secretions, or PM2.5.
[25] The composition is housed in an eye drop container formed from at least one selected from polypropylene, low-density polyethylene, high-density polyethylene, polyethylene terephthalate, polybutylene terephthalate, cycloolefin polymer, and cycloolefin copolymer. [14] The method according to any one of [24].
[26] The method of [25], wherein the eye drop container is a liquid-sprayable eye drop container.

Furthermore, the present invention also relates to:
[27] A composition for use in an eye-drop type eye wash, which has a viscosity of 12 mPa·s or less and is used so that 4 or more drops are instilled once per eye. thing.
[28] The composition for use according to [27], which is used so that 6 drops or less are instilled once per eye.
[29] A composition for use in instillation-type eyewashing, which has a viscosity of 12 mPa·s or less, and is characterized by being used so that the total amount of the ophthalmic solution is 120 μL or more once per eye. composition.
[30] The composition for use according to [29], which is used in such a way that the total volume of eye drops is 300 μL or less once per eye.
[31] Any one of [27] to [30], further containing at least one selected from the group consisting of antiphlogistic/astringent ingredients, antihistamine ingredients, inorganic salts, alkylpolyaminoethylglycine and boric acid or salts thereof A composition for use as described in .
[32] A composition for use according to any one of [27] to [30], further comprising boric acid.
[33] A composition for use according to any one of [27] to [32], further comprising a thickening agent.
[34] The composition for use according to any one of [27] to [33], further comprising a tonicity agent, a stabilizer, a pH adjuster and a solubilizer.
[35] The composition for use according to any one of [27] to [34], which has a pH of 6.5 or more and 7.0 or less.
[36] The composition for use according to any one of [27] to [35], which is used for washing away stains and foreign substances on the surface of the eye.
[37] The composition for use according to [36], wherein the dirt or foreign matter is pollen, ocular secretions or PM2.5.
[38] Housed in an eyedropper container formed from at least one selected from polypropylene, low-density polyethylene, high-density polyethylene, polyethylene terephthalate, polybutylene terephthalate, cycloolefin polymer, and cycloolefin copolymer [27] to [37] ].
[39] The composition for use according to [38], wherein the eye drop container is a liquid-sprayable eye drop container.

Furthermore, the present invention also relates to:
[40] The use of a composition having a viscosity of 12 mPa s or less for the manufacture of an eye drop eye wash, wherein the eye drop eye wash is applied in an amount of 4 drops or more once per eye. A use characterized in that it is used for
[41] The use according to [40], wherein the eye-drop type eye wash is used so that 6 drops or less are instilled once per eye.
[42] The use of a composition having a viscosity of 12 mPa·s or less for the manufacture of an eye-drop type eyewash, wherein the eye-drop type eye wash is administered once per eye with a total volume of eye drops of 120 μL or more. A use characterized in that it is used as is.
[43] The use according to [42], wherein the eye drop type eye wash is used in such a way that the total amount of eye drops is 300 μL or less once per eye.
[44] The composition further contains at least one selected from the group consisting of antiphlogistic/astringent components, antihistamine components, inorganic salts, alkylpolyaminoethylglycine and boric acid or salts thereof, [40]-[ 43].
[45] Use according to any one of [40] to [43], wherein the composition further contains boric acid.
[46] Use according to any one of [40] to [45], wherein the composition further contains a thickening agent.
[47] The use according to any one of [40] to [46], wherein the composition further contains a tonicity agent, a stabilizer, a pH adjuster and a solubilizer.
[48] The use according to any one of [40] to [47], wherein the composition has a pH of 6.5 or more and 7.0 or less.
[49] The use according to any one of [40] to [48], wherein the eye drops are used to wash away dirt and foreign matter from the surface of the eye.
[50] The use according to [49], wherein the dirt or foreign matter is pollen, ocular secretions or PM2.5.
[51] The composition is housed in an eye drop container formed from at least one selected from polypropylene, low-density polyethylene, high-density polyethylene, polyethylene terephthalate, polybutylene terephthalate, cycloolefin polymer, and cycloolefin copolymer, [ 40] to [50].
[52] The use according to [51], wherein the eye drop container is a liquid-sprayable eye drop container.

Furthermore, the present invention also relates to:
[53] An eye drop type eye wash having a viscosity of 12 mPa·s or less, characterized by being used so that 4 or more drops are instilled once per eye.
[54] The ophthalmic wash according to [53], which is used in such a way that 6 drops or less are instilled once per eye.
[55] An eye drop type eye wash having a viscosity of 12 mPa·s or less, which is used in such a manner that the total amount of the eye drops is 120 μL or more once per eye.
[56] The ophthalmic wash according to [55], which is used in such a way that the total amount of the ophthalmic solution is 300 μL or less once per eye.
[57] Any of [53] to [56], further containing at least one selected from the group consisting of antiphlogistic/astringent ingredients, antihistamine ingredients, inorganic salts, alkylpolyaminoethylglycine and boric acid or salts thereof The eye drop type eyewash according to .
[58] The ophthalmic wash solution according to any one of [53] to [56], further containing boric acid.
[59] The eye drop type eyewash of any one of [53] to [58], further containing a thickening agent.
[60] The eye drop type eye wash of any one of [53] to [59], further comprising a tonicity agent, a stabilizer, a pH adjuster and a solubilizer.
[61] The eye drop type eyewash according to any one of [53] to [60], which has a pH of 6.5 or more and 7.0 or less.
[62] The eye drop type eyewash of any one of [53] to [61], which is used for washing away stains and foreign substances on the surface of the eye.
[63] The eye drop type eyewash of [62], wherein the dirt or foreign matter is pollen, eye secretions or PM2.5.
[64] Housed in an eyedropper container formed from at least one selected from polypropylene, low-density polyethylene, high-density polyethylene, polyethylene terephthalate, polybutylene terephthalate, cycloolefin polymer, and cycloolefin copolymer [53] to [63] ] The eye drop type eye wash according to any one of the above.
[65] The eye drop type eyewash of [64], wherein the eye drop container is a liquid-sprayable eye drop container.

The above [1] to [65] can be arbitrarily selected and combined or applied mutatis mutandis.

By instilling 4 drops or more, preferably 4 drops or more and 6 drops or less, of an eye drop type eye wash medicinal composition having a viscosity of 12 mPa·s or less per eye once, it is close to or equivalent to a cup type eye wash. Or a better eye wash effect can be obtained. In addition, the eye drop type eye wash composition minimizes the contact of the eye wash with the skin around the eye, eyelashes, etc. compared to the cup type eye wash, and stains (sweat, pollen, etc.) adhering to the area around the eye , dust, etc.) into the eyes can be greatly reduced. can be expected to have a preventive and/or avoidance effect. Furthermore, when boric acid or a salt thereof and/or edetic acid or a salt thereof is further added to the ophthalmic eyewash composition, this composition has an effect of suppressing pollen burst. Therefore, in this case, it is also expected that the pollen can be washed away before the pollen bursts in the eye and the allergen inside the pollen is released.

FIG. 1 is a graph showing the relationship between the viscosity of an eye wash eye drop and its cleansing effect. FIG. 2 is a graph showing the relationship between the number of drops of the eye wash eye drop per eye and its cleaning effect. FIG. 3A is a graph showing pollen burst suppression effects of various components. FIG. 3B is a graph showing the pollen burst suppression effect of an aqueous solution containing various components. FIG. 4 is a graph showing the results of comparing intraocular contamination after eyewashing between the case of eyedrop type eyewashing and the case of cup type eyewashing.

The present invention will be described in detail below. In the present invention, "% (w/v)" means the mass (g) of the target component contained in 100 mL of the composition of the present invention (hereinafter the same unless otherwise specified).

The viscosity of the composition of the present invention is not particularly limited as long as it is low viscosity, specifically 12 mPa·s or less, and the viscosity is acceptable for eye drops. More specifically, the upper limit of the viscosity is preferably 10 mPa·s or less, more preferably 5 mPa·s or less, even more preferably 3 mPa·s or less, and particularly preferably 1 mPa·s or less. The lower limit of the viscosity is not particularly limited as long as it exceeds 0 mPa·s, but is preferably 0.01 mPa·s or more, more preferably 0.1 mPa·s or more, and particularly preferably 0.3 mPa·s or more. Moreover, the upper limit and lower limit of the viscosity can be appropriately combined to form a range. For example, it is preferably more than 0 mPa s and 10 mPa s or less, more preferably 0.01 mPa s or more and 5 mPa s or less, further preferably 0.1 mPa s or more and 3 mPa s or less, and 0.3 mPa s or more and 1 mPa s. The following are particularly preferred. In addition, in this specification, a low viscosity means the viscosity of 20 mPa*s or less, for example.

Moreover, the viscosity of the composition of the present invention can be measured, for example, by the viscosity measuring method described in the Japanese Pharmacopoeia 17th Edition. Specific measurement methods include a capillary viscometer method, a rotational viscometer method, and the like, and the rotational viscometer method is preferred. More specifically, the viscosity of each formulation can be measured at a shear rate of 100 s ⁻¹ and a measurement temperature of 25.0° C. using a cone-plate viscometer. Furthermore, the timing of measuring the viscosity of the composition of the present invention is not limited, but is preferably immediately after preparation of the composition of the present invention, immediately before use of the composition of the present invention, or at the expiry date of the composition of the present invention. It may be measured during the (effective period), more preferably immediately after preparation of the composition of the present invention or immediately before use of the composition of the present invention.

The number of times the composition of the present invention is used is not particularly limited as long as the number of instillations (eyewashes) is sufficient to achieve the desired effect. For example, 1 to 6 times/day is preferable, and 3 to 6 times/day is more preferable, but since the present invention is excellent in portability, it can be used immediately when a foreign object enters the eye. can.

The composition of the present invention is instilled into the eye once per eye, and as a lower limit, it is preferable to instill 3 drops or more, more preferably 4 drops or more. Although the upper limit is not particularly limited, it is preferable to instill 8 drops or less, preferably 6 drops or less, once per eye from the viewpoints of patient convenience, eye wash effect, problems due to increased eye wash drug amount, etc. is more preferable. Furthermore, the above upper limit and lower limit can be appropriately combined to form a range. For example, once per eye, it is preferable to instill 3 to 8 drops, more preferably 4 to 8 drops, and particularly preferably 4 to 6 drops.

Considering that the volume of one drop in a normal eye instillation is 30 to 50 μL, the lower limit of the total volume of eye drops per eye is preferably 90 μL or more, more preferably 120 μL or more. . Although the upper limit is not particularly limited, it is preferably 400 μL or less, more preferably 300 μL or less, once per eye from the viewpoints of patient convenience, eyewash effect, problems caused by increased eyewash drug amount, and the like. Furthermore, the above upper limit and lower limit can be appropriately combined to form a range. Specifically, for example, the range of the total volume of eye drops per eye is preferably 90 μL or more and 400 μL or less, more preferably 120 μL or more and 300 μL or less.

In the use of the composition of the present invention, "once per eye, n drops or more" means that n drops or more are continuously applied per eye per use. There are no particular restrictions on the blinking after instillation of the composition of the present invention. It doesn't have to be. From the viewpoint of the eye wash effect, it is preferable to blink every 1 or 2 drops, and more preferable to blink every 1 drop. The number of blinks is not particularly limited, but blinking is preferably 1 to 3 times, more preferably 1 to 2 times, after each drop or after multiple drops.

The composition of the present invention can contain the following components in appropriate amounts as long as they do not interfere with the effects of the present invention, and can be contained without particular limitations as long as they are pharmaceutically acceptable. In addition, it is desirable to contain the following ingredients as pharmacologically active ingredients (physiologically active ingredients or active ingredients). Specifically, epsilon-aminocaproic acid, allantoin, berberines (berberine chloride, berberine sulfate), sodium azulene sulfonate, dipotassium glycyrrhizinate, zincs (zinc sulfate, zinc lactate), lysozyme chloride, etc. anti-inflammatory and astringent ingredients, antihistamines such as diphenhydramine hydrochloride and chlorpheniramine maleate, flavin adenine dinucleotide sodium, cyanocobalamin, retinols (retinol acetate, retinol palmitate), pyridoxine hydrochloride, pantothenic acids (panthenol, calcium pantothenate, sodium pantothenate), vitamins such as tocopherol acetate, aspartates (potassium L-aspartate, magnesium L-aspartate, magnesium/potassium L-aspartate (equal mixture)), aminoethylsulfonic acid (taurine), Amino acids such as sodium chondroitin sulfate, inorganics such as potassium chloride, calcium chloride, sodium chloride, sodium hydrogen carbonate, sodium carbonate, dried sodium carbonate, magnesium sulfate, sodium hydrogen phosphate, sodium dihydrogen phosphate, and potassium dihydrogen phosphate. Examples thereof include salts, alkylpolyaminoethylglycine, boric acid, boric acid such as borax, and salts thereof, and more preferably boric acid, boric acid such as borax, or salts thereof.

The above components may be used alone or in any combination of two or more. When these components are contained as pharmacologically active components, the content is Depending on the type of ingredient, the type and content of other compounded ingredients, the application of the composition, the formulation form, the method of use, etc. Guideline 2017” (2) Ophthalmic drug manufacturing and marketing approval standards, it can be set as appropriate.

For example, the composition of the present invention can contain the pharmacologically active ingredient at the maximum concentration (% (w/v)) shown in Table 1 according to the above-mentioned OTC drug manufacturing and marketing approval standards.

For example, when the composition of the present invention contains the pharmacologically active ingredients of Group A shown in Table 1, it contains up to three pharmacologically active ingredients of Group B, and further contains up to one pharmacologically active ingredient of Group B and pharmacologically active ingredients of Groups C and D. It preferably contains up to three active ingredients each. In the case of containing the pharmacologically active ingredient of group B, it is preferable to contain only one type of pharmacologically active ingredient of group A, and further to contain up to three types of pharmacologically active ingredient of group C and group D, respectively. . Moreover, when the E or F group pharmacologically active ingredient is contained, it is preferable to contain only one type. In addition, when a subgroup exists in each group, it is preferable to contain only 1 type from the same subgroup.

When the composition of the present invention contains boric acid or boric acid such as borax or a salt thereof as a pharmacologically active ingredient (physiologically active ingredient or active ingredient), the content (concentration) thereof is pharmaceutically acceptable. If so, it is not particularly limited. For example, 0.01 to 5% (w/v) is preferred, 0.1 to 3% (w/v) is more preferred, and 0.5 to 1.2% (w/v) is particularly preferred.

The composition of the present invention may contain the following pharmaceutically acceptable pharmacologically active ingredients (physiologically active ingredients or active ingredients) in appropriate amounts in addition to the above-mentioned ingredients, as long as the effects of the present invention are not impaired. Specifically, decongestants (vasoconstrictors) such as epinephrine, epinephrine hydrochloride, ephedrine hydrochloride, tetrahydrozoline hydrochloride, naphazoline hydrochloride, naphazoline nitrate, phenylephrine hydrochloride, dl-methylephedrine hydrochloride, neostigmine methyl sulfate, tropicamide, helenien, sulfuric acid Ingredients for adjusting eye muscles (focus adjusting ingredients) such as atropine, zinc sulfate hydrate, pranoprofen, salicylic acid, tranexamic acid, anti-inflammatory and astringent ingredients such as licorice, cromoglycic acid or its salt (sodium cromoglycate), amlexanox, ibudilast , suplatast, pemirolast or its salts (pemirolast potassium, pemirolast sodium), tranilast, olopatadine or its salts (olopatadine hydrochloride), levocabastine or its salts (levocabastine hydrochloride), acitazanolast, ketotifen or its salts (fumaric acid ketotifen), antihistamines or antiallergic agents such as epinastine or its salts (epinastine hydrochloride), vitamin B ₁₂ (hydroxocobalamin, methylcobalamin and adenosylcobalamin), vitamin B ₆ (pyridoxine, pyridoxal, pyridoxamine), vitamin E (acetic acid- d-α tocopherol), vitamin B ₁ (thiamine, thiamine hydrochloride), niacin (nicotinic acid and nicotinamide), biotin, vitamins such as folic acid, aspartic acid, glycine, alanine, γ-aminobutyric acid, glutamic acid, arginine , amino acids such as lysine, sulfa drugs such as sulfamethoxazole, sulfamethoxazole sodium, sulfisoxazole, sulfisoxazole sodium, polyvinyl alcohol, polyvinylpyrrolidone, hydroxyethylcellulose, hydroxypropylmethylcellulose, methylcellulose , viscous ingredients such as glucose, acrinol, cetylpyridinium, benzalkonium chloride, benzethonium chloride, chlorhexidine, polyhexamethylene biguanide, alkyldiaminoethylglycine hydrochloride, etc., corneal protection, corneal disorder treatment, such as sodium hyaluronate ingredients and the like. The composition of the present invention may not contain sodium hyaluronate at a concentration of 0.075% (w/v) as a pharmacologically active ingredient, and may contain substantially or no sodium hyaluronate. good too. It may also contain substantially or no polyhexamethylene biguanide.

The pharmacologically active ingredients (physiologically active ingredients or active ingredients) that can be used in the composition of the present invention may be used singly or in any combination of two or more. Furthermore, the content of the pharmacologically active ingredient can be appropriately set according to the type of pharmacologically active ingredient, the type and content of other compounding ingredients, the application of the composition, the formulation form, the method of use, and the like.

The composition of the present invention may further contain a thickening agent, a tonicity agent, a stabilizer, a pH adjusting agent and/or a solubilizing agent.

The thickening agent that can be used in the composition of the present invention is not particularly limited as long as it is pharmaceutically acceptable. For example, polyvinylpyrrolidone K25, polyvinylpyrrolidone K30, polyvinylpyrrolidone K90 and other polyvinylpyrrolidones, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose 2208, hydroxypropylmethylcellulose 2906, hydroxypropylmethylcellulose, carboxymethylcellulose, carboxyethylcellulose, Cellulose derivatives such as nitrocellulose or salts thereof, polyethylene glycols such as Macrogol 300, Macrogol 400, Macrogol 1500, Macrogol 4000, and Macrogol 6000, Dextrans such as Dextran 40 and Dextran 70, Sodium hyaluronate (purified sodium hyaluronate, etc.), hyaluronic acid derivatives such as crosslinked hyaluronic acid, alginic acid, alginic acid derivatives such as sodium alginate, polyvinyl alcohol, carboxyvinyl polymer, sodium chondroitin sulfate, gum arabic, gellan gum, tragacanth, polyvinylpyrrolidone K25, Polyvinylpyrrolidones such as polyvinylpyrrolidone K30 and polyvinylpyrrolidone K90, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose 2208, hydroxypropylmethylcellulose 2906, hydroxypropylmethylcellulose, carboxymethylcellulose, carboxyethylcellulose, nitrocellulose, or salts thereof etc., hyaluronic acid derivatives such as crosslinked hyaluronic acid, alginic acid derivatives such as alginic acid and sodium alginate, and polyvinylpyrrolidone K30 is more preferred. The composition of the present invention may substantially or completely contain no sodium hyaluronate (purified sodium hyaluronate, etc.).

The thickening agents that can be used in the composition of the present invention may be used alone or in any combination of two or more. Furthermore, the content of the thickening agent can be appropriately set according to the type of thickening agent, the type and content of other ingredients, the application of the composition, the formulation form, the method of use, and the like.

When a thickening agent is used in the composition of the present invention, the total content (concentration) of the thickening agent is, for example, preferably 0 to 1.0% (w/v), and 0.01 to 0.5%. (w/v) is more preferred, and 0.1 to 0.3% (w/v) is particularly preferred.

The tonicity agent that can be used in the composition of the present invention is not particularly limited as long as it is pharmaceutically acceptable. For example, potassium salts such as potassium chloride and potassium acetate, calcium salts such as calcium chloride, sodium chloride, sodium hydrogen carbonate, sodium carbonate, dry sodium carbonate, sodium acetate, sodium hydrogen sulfite, sodium sulfite, sodium thiosulfate and other sodium salts , magnesium sulfate, inorganic salts such as magnesium salts such as magnesium chloride, polyhydric alcohols such as glycerin, propylene glycol, polyethylene glycol, mannitol, sorbitol, xylitol, trometamol, etc., potassium chloride, calcium chloride, calcium chloride, chloride Sodium, sodium hydrogen carbonate, sodium carbonate, dry sodium carbonate or magnesium sulfate are preferred, and potassium chloride and sodium chloride are more preferred.

The isotonizing agents that can be used in the composition of the present invention may be used singly or in any combination of two or more. Furthermore, the content of the tonicity agent can be appropriately set according to the type of the tonicity agent, the type and content of other ingredients, the application of the composition, the formulation form, the method of use, and the like.

When a tonicity agent is used in the composition of the present invention, the total content (concentration) of the tonicity agent is, for example, preferably 0.05 to 5% (w/v), and 0.1 to 1.5% (w/v). 8% (w/v) is more preferred, and 0.3-0.9% (w/v) is particularly preferred.

The stabilizer that can be used in the composition of the present invention is not particularly limited as long as it is pharmaceutically acceptable. For example, trometamol, sodium formaldehyde sulfoxylate (Rongalite), tocopherol, sodium pyrosulfite, monoethanolamine, aluminum monostearate, glyceryl monostearate, dibutylhydroxytoluene, edetic acid, sodium edetate, sodium edetate hydrate , polyoxyethylene polyoxypropylene glycol and the like, preferably dibutylhydroxytoluene, edetic acid, sodium edetate or sodium edetate hydrate, more preferably sodium edetate hydrate.

The stabilizers that can be used in the composition of the present invention may be used alone or in any combination of two or more. Furthermore, the content of the stabilizer can be appropriately set according to the type of stabilizer, the type and content of other ingredients, the application of the composition, the formulation form, the method of use, and the like.

When a stabilizer is used in the composition of the present invention, the total content (concentration) of the stabilizer is, for example, preferably 0.0001 to 1% (w/v), preferably 0.001 to 0.5% (w/v). /v) is more preferred, and 0.005 to 0.1% (w/v) is particularly preferred.

The pH adjuster that can be used in the composition of the present invention is not particularly limited as long as it is pharmaceutically acceptable. For example, dilute hydrochloric acid, acetic acid, sodium hydroxide, sodium hydrogencarbonate, sodium carbonate and the like can be mentioned, with dilute hydrochloric acid and sodium hydroxide being preferred.

The pH adjusters that can be used in the composition of the present invention may be used singly or in any combination of two or more. Furthermore, the content of the pH adjuster can be appropriately set according to the type of pH adjuster, the type and content of other ingredients, the application of the composition, the formulation form, the method of use, and the like.

When a pH adjusting agent is used in the composition of the present invention, the total content (concentration) of the pH adjusting agent is, for example, preferably 0 to 5% (w/v), 0.005 to 1% (w/v ) is more preferred, and 0.01 to 0.5% (w/v) is particularly preferred.

The pH of the composition of the present invention is not particularly limited as long as it is pharmaceutically acceptable, but the upper limit is preferably 7.5 or less, more preferably 7.2 or less, and particularly preferably 7.0 or less. . Moreover, the lower limit thereof is preferably 5.0 or more, more preferably 6.0 or more, and particularly preferably 6.5 or more. Moreover, the upper limit and the lower limit of the above pH can be appropriately combined to form a range. Specifically, for example, it is preferably 5.0 or more and 7.5 or less, more preferably 6.0 or more and 7.2 or less, and particularly preferably 6.5 or more and 7.0 or less.

The pH can be measured, for example, according to the pH measurement method described in the Japanese Pharmacopoeia 17th Edition.

The dissolving agent (solvent and/or dispersion medium) that can be used in the composition of the present invention is not particularly limited as long as it is pharmaceutically acceptable. Examples include water (distilled water, ordinary water, purified water, sterilized purified water, water for injection, distilled water for injection, etc.), water-containing ethanol and other aqueous dissolving agents, and water (distilled water, ordinary water, purified water, sterilized water, etc.). purified water, water for injection, distilled water for injection, etc.) are preferred.

The dissolving agents that can be used in the composition of the present invention may be used singly or in any combination of two or more. Furthermore, the content of the dissolving agent can be appropriately set according to the type of dissolving agent, the type and content of other ingredients, the application of the composition, the formulation form, the method of use, and the like.

In the composition of the present invention, for example, when the dissolving agent is water, the total amount of the composition is preferably 90% (w/v) or more, more preferably 95% (w/v) or more, and 97% (w/v) or more. w/v) or more is particularly preferred.

The composition of the present invention may contain an appropriate amount of additives other than the aforementioned additives (thickening agent, tonicity agent, stabilizer, pH adjuster, solubilizer) as long as the effects of the present invention are not hindered. can. Additives other than the above-mentioned additives are not particularly limited as long as they are pharmaceutically acceptable, and for example, surfactants (solubilizers), buffers, preservatives, cooling agents and the like can be used.

Surfactants (solubilizers) that can be used in the composition of the present invention are not particularly limited as long as they are pharmaceutically acceptable. For example, nonionic surfactants, amphoteric surfactants, anionic surfactants, cationic surfactants and the like are preferred, and nonionic surfactants are more preferred.

Examples of nonionic surfactants include POE (20) sorbitan monolaurate (polysorbate 20), POE (20) sorbitan monopalmitate (polysorbate 40), POE (20) sorbitan monostearate (polysorbate 60), POE sorbitan fatty acid esters such as POE (20) sorbitan stearate (polysorbate 65), POE (20) sorbitan monooleate (polysorbate 80), POE (40) hydrogenated castor oil (polyoxyethylene hydrogenated castor oil 40) and POE ( 60) POE hydrogenated castor oil such as hydrogenated castor oil (polyoxyethylene hydrogenated castor oil 60), POE (10) castor oil (polyoxyethylene castor oil 10), POE (35) castor oil (polyoxyethylene castor oil 35) POE castor oil such as POE (9) POE alkyl ether such as lauryl ether, POE-POP alkyl ether such as POE (20) POP (4) cetyl ether, POE (54) POP (39) glycol, POE (120) POP (40) glycol, POE (160) POP (30) glycol, POE (196) POP (67) glycol (poloxamer 407, Pluronic F127), POE (200) POP (70) glycol, and other polyoxyethylene polyoxy Propylene block copolymers, polyethylene glycol monostearate such as polyoxyl 40 stearate, POE (20) sorbitan monolaurate (polysorbate 20), POE (20) sorbitan monopalmitate (polysorbate 40), POE monostearate ( 20) POE sorbitan fatty acid esters such as sorbitan (polysorbate 60), POE (20) sorbitan tristearate (polysorbate 65), POE (20) sorbitan monooleate (polysorbate 80) are preferred, and POE (20) sorbitan monooleate (Polysorbate 80) is more preferred.

Examples of amphoteric surfactants include N-[2-[[2-(alkylamino)ethyl]amino]ethyl]glycine and salts thereof.

Examples of anionic surfactants include alkylbenzenesulfonates, alkylsulfates, polyoxyethylene alkylsulfates, α-sulfofatty acid ester salts, α-olefinsulfonic acids and the like.

Examples of cationic surfactants include benzalkonium chloride, benzethonium chloride, chlorhexidine gluconate, and the like.

These surfactants may be used alone or in any combination of two or more. Furthermore, the content of the surfactant can be appropriately set according to the type of surfactant, the type and content of other ingredients, the application of the composition, the formulation form, the method of use, and the like.

When a surfactant is used in the composition of the present invention, for example, the total content (concentration) of the surfactant is preferably 0.01 to 5% (w/v), 0.01 to 1% (w/v /v) is more preferred, and 0.05 to 0.5% (w/v) is even more preferred.

The buffering agent that can be used in the composition of the present invention is not particularly limited as long as it is pharmaceutically acceptable. For example, boric acid or its salts such as boric acid, sodium borate, potassium tetraborate, potassium metaborate, ammonium borate, borax, phosphoric acid, disodium hydrogen phosphate, sodium dihydrogen phosphate, dihydrogen phosphate Phosphoric acid or its salts such as potassium, trisodium phosphate, tripotassium phosphate, calcium monohydrogen phosphate, calcium dihydrogen phosphate, carbonic acid, sodium hydrogen carbonate, sodium carbonate, ammonium carbonate, potassium carbonate, calcium carbonate, carbonate Carbonic acid or its salts such as potassium hydrogen and magnesium carbonate, citric acid, sodium citrate, potassium citrate, calcium citrate, sodium dihydrogen citrate, citric acid or its salts such as disodium citrate, acetic acid, ammonium acetate, Acetic acid or its salts such as potassium acetate, calcium acetate, sodium acetate, aspartic acid, sodium aspartate, magnesium aspartate, aspartic acid or its salts such as potassium aspartate, ethylenediaminediacetic acid (EDDA), ethylenediaminetriacetic acid, ethylenediaminetetraacetic acid Ethylenediamineacetic acid such as acetic acid (edetic acid, EDTA), disodium ethylenediaminetetraacetic acid hydrate (sodium edetate hydrate), N-(2-hydroxyethyl)ethylenediaminetriacetic acid (HEDTA), diethylenetriaminepentaacetic acid (DTPA) or salts thereof, amino acids such as ε-aminocaproic acid, etc., boric acid, sodium borate, potassium tetraborate, potassium metaborate, ammonium borate, boric acid or its salts such as borax, phosphoric acid, phosphorus Phosphoric acid or its salts such as disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, trisodium phosphate, tripotassium phosphate, calcium monohydrogen phosphate, calcium dihydrogen phosphate, and ε-aminocaproic acid are preferred, and boric acid, borax, or ε-aminocaproic acid are more preferred.

The buffering agents that can be used in the composition of the present invention may be used singly or in any combination of two or more. Furthermore, the content of the buffering agent can be appropriately set according to the type of buffering agent, the type and content of other ingredients, the application of the composition, the formulation form, the method of use, and the like.

When a buffering agent is used in the composition of the present invention, for example, the total content (concentration) of the buffering agent is preferably 0.001-5% (w/v), 0.005-3% (w/v ) is more preferred, and 0.01 to 2% (w/v) is particularly preferred.

Preservatives that can be used in the composition of the present invention are not particularly limited as long as they are pharmaceutically acceptable. For example, polyhexamethylene biguanide, biguanide compounds such as polyhexanide hydrochloride, zinc chloride, alkyldiaminoethylglycine hydrochloride, sodium benzoate, ethanol, benzalkonium chloride, benzethonium chloride, chlorhexidine gluconate, chlorobutanol, sorbic acid, potassium sorbate , Sodium dehydroacetate, Methyl parahydroxybenzoate, Ethyl parahydroxybenzoate, Propyl parahydroxybenzoate, Butyl parahydroxybenzoate, Oxyquinoline sulfate, Phenethyl alcohol, Benzyl alcohol, Glokyl (manufactured by Rhodia), Boric acid, Borax, Chlorous acid and the like, preferably benzalkonium chloride, chlorhexidine gluconate, sorbic acid, phenethyl alcohol, boric acid, borax, chlorous acid, benzalkonium chloride, chlorhexidine gluconate, phenethyl alcohol, boric acid, Borax and chlorous acid are more preferred. The composition of the present invention may contain substantially or no polyhexamethylene biguanide.

The preservatives that can be used in the composition of the present invention may be used singly or in any combination of two or more. Furthermore, the content of the preservative can be appropriately set according to the type of preservative, the type and content of other ingredients, the application of the composition, the formulation form, the method of use, and the like.

When a preservative is used in the composition of the present invention, for example, the total content (concentration) of the preservative is preferably 0.0001 to 1% (w/v), 0.0005 to 0.5% (w/v), /v), more preferably 0.001 to 0.2% (w/v), but preservatives, especially benzalkonium or salts thereof, or methyl parahydroxybenzoate, ethyl parahydroxybenzoate, parahydroxybenzoic acid Compositions that are substantially or completely free of parabens such as propyl, butyl paraoxybenzoate or salts thereof are particularly preferred.

The cooling agent that can be used in the composition of the present invention is not particularly limited as long as it is pharmaceutically acceptable. For example, essential oils containing terpenoids such as eucalyptus oil, bergamot oil, peppermint oil, fennel oil, rose oil, cinnamon oil, spearmint oil, camphor oil, cool mint, peppermint oil, menthol, menthone, camphor, borneol, geraniol, nerol , cineole, citronellol, carvone, anethole, eugenol, limonene, linalool, linalyl acetate, and the like, menthol, camphor, borneol and geraniol are preferred, and menthol and borneol are more preferred. In addition, the terpenoid may be any of d-, l-, and dl-forms, such as l-menthol, d-menthol, dl-menthol, dl-camphor, d-camphor, dl-borneol, d-borneol, and the like. and l-menthol, dl-camphor, d-camphor and d-borneol are preferred.

The cooling agents that can be used in the composition of the present invention may be used alone or in any combination of two or more. Furthermore, the content of the cooling agent can be appropriately set according to the type of cooling agent, the type and content of other compounding ingredients, the application of the composition, the formulation form, the method of use, and the like.

When a cooling agent is used in the composition of the present invention, for example, the total content (concentration) of the cooling agent is preferably 0.001 to 0.5% (w/v), more preferably 0.001 to 0.5% (w/v). 1% (w/v) is more preferred, and 0.005-0.05% (w/v) is particularly preferred.

Among the above components, the composition of the present invention preferably contains boric acid or a salt thereof and/or edetic acid or a salt thereof, and optionally polyvinylpyrrolidone, because it exhibits an effect of inhibiting pollen bursting.

The osmotic pressure of the composition of the present invention is not particularly limited as long as it is pharmaceutically acceptable. For example, the osmotic pressure ratio is preferably 0.2 to 2, more preferably 0.7 to 1.5, and particularly preferably 1.0 to 1.2.

The osmotic pressure ratio is the ratio of the osmotic pressure of the sample to 286 mOsm (osmotic pressure of 0.9% (w / v) sodium chloride aqueous solution) based on the 17th revision of the Japanese Pharmacopoeia, and the osmotic pressure is described in the Japanese Pharmacopoeia. The standard solution for osmotic pressure ratio measurement (0.9% (w/v) sodium chloride aqueous solution) can be measured using sodium chloride (Japanese Pharmacopoeia standard reagent ) is dried at 500 to 650 ° C. for 40 to 50 minutes, then allowed to cool in a desiccator (silica gel), accurately weigh 0.900 g, dissolve in purified water to make exactly 100 mL, or prepare a commercially available osmotic pressure ratio A standard solution for measurement (0.9% (w/v) sodium chloride aqueous solution) can be used.

The composition of the present invention can be accommodated in any container (main body, inner plug, cap) and provided. Moreover, the container containing this composition is not particularly limited as long as it is pharmaceutically acceptable. For example, glass containers and polypropylene, low density polyethylene, high density polyethylene, polyethylene terephthalate, polybutylene terephthalate, cycloolefin polymer, cycloolefin copolymer, polyarylate, polyethylene naphthalate, polycarbonate, polytetrafluoroethylene, polyimide, polymethylpentene , copolymers of the monomers that constitute them, and plastic containers that combine two or more of these materials. Polypropylene, low-density polyethylene, high-density polyethylene, polyethylene terephthalate, polybutylene terephthalate, cycloolefin polymer and cycloolefin copolymers, copolymers of monomers constituting these, and plastic containers in which two or more of these materials are combined are preferred. Here, the combination may be a mixture of different materials, or a layered structure of different materials. Further, the container may be a reusable multi-dose container, a single-use unit-dose container, or a reusable multi-dose container that can be sprayed. is preferred. The container containing these compositions of the present invention is, for example, a general eye drop container. It is

The compositions of the present invention are used, for example, to wash away dirt and foreign matter from the ocular surface. In the present invention, "washing away dirt and foreign matter" means washing away dirt and foreign matter on the surface of the eye from the inside of the eye to the outside of the eye.

In the present invention, "dirt or foreign matter" is not particularly limited as long as it is a substance that causes discomfort to the eyes. For example, pollen of cedar, cypress, gramineous plants, etc., dust such as house dust, eye secretions such as protein, skin secretions such as sweat, PM2.5, eye shadow, mascara, cosmetics such as foundation, etc. , pollen of cedar, cypress, gramineous plants, etc., and PM2.5 are preferred.

The composition of the present invention can be used, for example, as a composition for contact lenses, can be applied to any commercially available contact lenses including hard contact lenses and/or soft contact lenses, and can be applied to contact lenses while wearing them ( It can also be used with a contact lens attached to the eye surface. Here, soft contact lenses include, for example, both ionic and non-ionic, and include both silicone hydrogel contact lenses and non-silicone hydrogel contact lenses. It also includes all soft contact lenses classified as Groups I-IV.

The composition of the present invention may be labeled as "can be used when wearing contact lenses (hard contact lenses/soft contact lenses)" or "for use when wearing contact lenses (hard contact lenses/soft contact lenses)". You can also have a display similar to them. In addition, the labeling can be direct or indirect, and examples of direct labeling include descriptions on packaging such as the product itself, packages, containers, labels, tags, etc. Indirect labeling Examples include advertising, publicity, explanations to doctors through transaction documents, instruction manuals, attached documents, catalogs, websites, stores, exhibitions, signboards, bulletin boards, newspapers, magazines, TV, radio, e-mail, etc. and other activities.

In addition, the detailed description of the composition of the present invention, etc. described above also applies to the following aspects of the present invention.

One aspect of the present invention is an instillation-type eyewashing method including instilling 4 or more drops of a composition having a viscosity of 12 mPa·s or less per eye once.

One aspect of the present invention is a composition for use in an eye-drop eye wash, which has a viscosity of 12 mPa·s or less and is used so that 4 or more drops are instilled once per eye. A composition characterized.

One aspect of the present invention is the use of a composition having a viscosity of 12 mPa·s or less for the manufacture of an eye drop eye wash, wherein the eye wash is administered 4 drops or more once per eye. A use characterized in that it is used as instilled into the eye.

One aspect of the present invention is an eye drop type eye wash having a viscosity of 12 mPa·s or less, wherein the eye drop type eye wash is characterized by being used so that 4 or more drops are instilled once per eye. be.

<Formulation example>
Examples of formulations of the present invention are shown in Table 2 below, which are provided for better understanding of the present invention and do not limit the scope of the present invention. In addition, in the formulation examples below, the amount of each component to be blended is the content in 100 mL of the formulation, and the viscosity thereof is 12 mPa·s or less.

A desired composition having a viscosity of 12 mPa·s or less can be obtained by appropriately adjusting the types and amounts of the pharmacologically active ingredients and additives and the viscosity in Formulation Examples 1 to 6 above.

<Example>
Below, as an example, 1. 2. Correlation test between the number of drops per eye and washing effect;3. 3. pollen burst suppression effect test; Intraocular contamination confirmation test of eye drops type eye wash and cup type eye wash is shown. However, these test examples are for better understanding of the present invention and do not limit the scope of the present invention.

(Test example 1)
1. Correlation Test between Viscosity of Eye Drops for Washing Eyes and Cleansing Effect The following test was conducted to investigate the relationship between the viscosity of eye drops for eye washes (eye wash solution) and its cleansing effect in the case of eye wash.

1) Preparation of ophthalmic solution for washing eyes (test solution) First, 8700 mL of water was heated to 50°C and mixed with 100.0 g of boric acid, 50.0 g of polyvinylpyrrolidone K30, 1.0 g of sodium edetate hydrate, and sodium chloride. 40.0 g and 10.0 g of potassium chloride are stirred, and after cooling to room temperature, dilute hydrochloric acid/sodium hydroxide is added to adjust the pH to 6.7, and water is added to make the total volume 10000 mL. An eye drop 1 for eye wash was prepared. At this time, the viscosity of the low-viscosity eye wash eyedrops 1 was 0.84 mPa·s. Next, add and disperse 3.0 g of hydroxymethyl cellulose (HEC) in 1 150 mL of low-viscosity eye wash eye drops, heat to 70° C., stir and dissolve. prepared in Then, 6 mL of this viscosity-adjusting ophthalmic solution and 34 mL of low-viscosity eye-washing eye drop 1 were thoroughly stirred together to form low-viscosity eye-washing eye drop 2 having a viscosity of 11.56 mPa·s with 12 mL of viscosity-adjusting eye drop. 1 28 mL of the low-viscosity eye wash solution is mixed well to obtain a high-viscosity eye wash solution 1 having a viscosity of 56.4 mPa s, and 20 mL of the viscosity-adjusting eye drop solution and 1 20 mL of the low-viscosity eye wash solution are combined. A highly viscous eye wash eye drop 2 having a viscosity of 194.2 mPa·s was prepared by stirring well. The viscosity was measured immediately before the test using a cone-plate viscometer at a shear rate of 100 s ⁻¹ and a measurement temperature of 25.0° C. based on the Japanese Pharmacopoeia 17th Edition. Table 3 shows the viscosity of each eye wash eye drop.

2) Test method Male Japanese white rabbits were used for the cleaning effect test. The experimental subject is one animal with both eyes and two eyes. Animals were given general anesthesia and ocular surface anesthesia, and spherical fluorescent beads having an average diameter of about 40 μm were uniformly suspended (3% suspension, Spherotech Inc. 1% spherical fluorescent bead suspension was concentrated). 50 μL of each eye was instilled. After that, the above-described eye wash eye drops were administered by pipetman in an amount of 4 drops per eye (46 μL 4 times) to wash the eye surface by eye drop type eye wash. After washing, the fluorescent beads remaining on the ocular surface were collected with a Pipetman. The volume of the collected liquid containing the fluorescent beads was measured with a Pipetman (x μL). A portion of the collected liquid was placed on a Fuchs-Rosenthal type hemocytometer, and the bead density was measured with an optical microscope according to the method for using the hemocytometer (y/μL). The number (pieces) of the collected fluorescent beads was calculated from the volume (x μL) of the collected liquid and the density of the beads (y pieces/μL) by the formula (x×y), and was defined as the number of beads (b) remaining after washing the eyes. In addition, the collecting operation was performed without administering the eye drops for eye washing, and the number of collected fluorescent beads was calculated in the same manner. This was defined as the number of remaining beads (a) without washing. The residual rate of beads after eye washing with each eye wash eye drop was calculated according to the following formula 1. Here, a low bead residual rate means a high cleaning effect. The bead remaining rate without washing was 100%.
[Formula 1]
Percentage of beads remaining (%) = {Number of beads remaining after washing (b) / Number of beads remaining without washing (a)} x 100

3) Test results and discussion Test results are shown in Table 4 and FIG. Here, FIG. 1 is a graph plotting the viscosity (mPa·s) of eye drops for washing eyes on the horizontal axis and the bead residual rate (%) on the vertical axis.

As shown in Table 4 and FIG. 1, the cleansing effect (indicated as the bead residual rate) of the low-viscosity eye wash solution 1 (0.84 mPa s) and the low-viscosity eye wash solution 2 (11.56 mPa s) was , 15% or less. Among them, the cleansing effect of the low-viscosity eye wash eye drop 1 (0.84 mPa·s) was extremely excellent with a bead residual rate of 3.0%. In addition, the bead retention rate of the high-viscosity eye wash eyedrops 1 (56.4 mPa s) increased from the bead retention rate (14.7%) of the low-viscosity eye wash eye drops 2 (11.56 mPa s), It was 39.6%. From the above, it was shown that the cleansing effect of the eye drops for eye washing rapidly decreases when the viscosity exceeds about 12 mPa·s.

(Test example 2)
2. Correlation test between the number of eye drops per eye and washing effect The following test was conducted, and the number of drops of the eye wash solution (eye wash solution) per eye in the case of eye wash. and its relationship with its cleaning effect.

1) Preparation of Eye Drops for Washing Eyes (Test Solution) An eye drop for washing eyes (viscosity: 0.84 mPa·s) having the same composition as the eye drop for low-viscosity eye drops 1 in Test Example 1 was used.

2) Test method Test subjects were two eyes and four eyes of two male Japanese white rabbits. Using a pipetman, eye wash eye drops were administered in 2, 4, 6, and 8 drops per eye (46 μL each 2, 4, 6, and 8 times) to wash the eyes, except that the eyes were washed. A test was conducted in the same manner, and the residual rate of beads after washing the eyes was calculated for each number of eye drops. In addition, as a reference example, instead of the eye-drop type eye wash, a cup-type eye wash was performed by contacting the eye surface of the animal with 5 mL of eye wash eye drops using an eye wash cup attached to a commercially available cup-type eye wash (manufactured by Rohto Pharmaceutical Co., Ltd.). The test was performed in the same manner except that the eyes were washed, and the bead retention rate was calculated.

3) Test results and discussion Test results are shown in Table 5 and FIG. Here, FIG. 2 is a graph showing the relationship between the dose of each eye wash eye drop (the number of drops per eye, cup-type eye wash as a reference example) and the bead residual rate (%). The bead remaining rate without washing was 100%.

As shown in Table 5 and FIG. 2, when 4 drops or more of the eye wash eye drops per eye were used for eye wash, the bead retention rate was 2% or less, indicating an excellent washing effect. In addition, the cleaning effect of the eye drop type eye wash with 4 drops or more per eye was superior to the cup type eye wash using the existing eye wash cup. From the above, it was shown that a sufficient effect of removing foreign substances from the ocular surface can be obtained by washing the eyes with 4 or more drops of the eye wash eye drops per eye.

(Test example 3)
3. Pollen burst suppression effect test 3-1. Effect of Inhibiting Pollen Burst of Various Ingredients The following test was conducted to investigate the effect of various ingredients in inhibiting pollen bursting.

1) Preparation of test liquid 12.5 g of disodium hydrogen phosphate hydrate was added to 900 mL of water, stirred and dissolved, and water was added to make the total volume 1000 mL. 40 mL of the 1.25-fold solution 1 was taken, diluted hydrochloric acid/sodium hydroxide was added to adjust the pH to 7.0, and water was added to bring the total volume to 50 mL. 0.05 g of potassium chloride was added to 40 mL of 1.25-fold solution 1, and stirred and dissolved. Diluted hydrochloric acid/sodium hydroxide was added to this liquid to adjust the pH to 7.0, and water was added to adjust the total volume to 50 mL. 0.2 g of sodium chloride was added to 40 mL of the 1.25-fold solution 1, and stirred and dissolved. Diluted hydrochloric acid/sodium hydroxide was added to this liquid to adjust the pH to 7.0, and water was added to bring the total volume to 50 mL. 0.5 g of boric acid was added to 40 mL of 1.25-fold solution 1, and stirred and dissolved. Diluted hydrochloric acid/sodium hydroxide was added to this liquid to adjust the pH to 7.0, and water was added to bring the total volume to 50 mL. 0.05 g of sodium edetate hydrate was added to 40 mL of the 1.25-fold solution 1, and stirred and dissolved. Diluted hydrochloric acid/sodium hydroxide was added to this liquid to adjust the pH to 7.0, and water was added to make the total volume 50 mL to obtain test liquid 5. 0.25 g of polyvinylpyrrolidone K30 was added to 40 mL of 1.25 times liquid 1, and stirred and dissolved. Diluted hydrochloric acid/sodium hydroxide was added to this liquid to adjust the pH to 7.0, and water was added to bring the total volume to 50 mL. Table 6 shows the compositions of the aqueous solutions of test liquids 1 to 6. Here, disodium hydrogen phosphate hydrate was contained as a pH buffer. Also, test liquids 1 to 6 had viscosities of 12 mPa·s or less.

2) Test method 50 µL of each test liquid was dropped into about 3 µL of cedar pollen particles. After 5 minutes, ruptured and unruptured vacuoles were counted under an optical microscope. The pollen burst rate was calculated according to Equation 2 below.
[Formula 2]
Pollen rupture rate (%) = {number of ruptured vacuoles / (number of ruptured vacuoles + number of unruptured vacuoles)} x 100

3) Test results and discussion The test results are shown in FIG. 3A. Here, FIG. 3A is a graph showing the pollen burst rate of each test liquid. Here, the aqueous solution containing boric acid or sodium edetate hydrate had a pollen burst rate of 15% or less, and exhibited an excellent pollen burst inhibitory effect. On the other hand, an aqueous solution containing potassium chloride, sodium chloride or polyvinylpyrrolidone K30 showed a pollen bursting promoting effect.

3-2. Pollen Burst Suppressive Effect of Various Compositions The following tests were conducted to investigate the pollen burst inhibitory effect of various compositions.

1) Preparation of Test Solution 160 mL of water was heated to 45° C., 2.5 g of boric acid, 1.0 g of sodium chloride and 0.25 g of potassium chloride were added and stirred. After the liquid was cooled to room temperature, water was added to adjust the total volume to 200 mL, which was used as 1.25-fold liquid 2. 40 mL of the 1.25-fold solution 2 was taken, diluted hydrochloric acid/sodium hydroxide was added to adjust the pH to 7.2, and water was added to bring the total volume to 50 mL. 40 mL of 1.25 times solution 2 was heated to 45° C., 0.40 g of boric acid was added, and the mixture was stirred. After the liquid was cooled to room temperature, dilute hydrochloric acid/sodium hydroxide was added to adjust the pH to 7.2, and water was added to bring the total volume to 50 mL to obtain test liquid 8. 40 mL of 1.25 times solution 2 was heated to 45° C., 0.025 g of sodium edetate hydrate was added and stirred. After the liquid was cooled to room temperature, dilute hydrochloric acid/sodium hydroxide was added to adjust the pH to 7.2, and water was added to bring the total volume to 50 mL to obtain test liquid 9. 40 mL of 1.25 times solution 2 was heated to 45° C., 0.05 g of sodium edetate hydrate was added and stirred. After the liquid was cooled to room temperature, dilute hydrochloric acid/sodium hydroxide was added to adjust the pH to 7.2, and water was added to bring the total volume to 50 mL. 12.0 g of boric acid, 4.8 g of sodium chloride, 1.2 g of potassium chloride, 0.12 g of sodium edetate hydrate, and 6.0 g of polyvinylpyrrolidone K30 were added to 800 mL of water and stirred. Water was added to the liquid to make a total volume of 960 mL, which was used as 1.25-fold liquid 3. 320 mL of the 1.25-fold solution 3 was taken, diluted hydrochloric acid/sodium hydroxide was added to adjust the pH to 7.0, and water was added to bring the total volume to 400 mL to prepare a test solution 11 . 320 mL of the 1.25-fold solution 3 was taken, diluted hydrochloric acid/sodium hydroxide was added to adjust the pH to 6.5, and water was added to bring the total volume to 400 mL to prepare a test solution 12 . Table 7 shows the compositions of the aqueous solutions of test liquids 7 to 12. Test liquids 7 to 12 had viscosities of 12 mPa·s or less.

2) Test method A test was performed according to the method described in “3-1. Pollen burst suppression effect of various ingredients 2) Test method”.

3) Test results and discussion The test results are shown in FIG. 3B. Here, FIG. 3B is a graph showing the pollen burst rate of each test solution. Here, test liquids 7 to 12 had a pollen burst rate of 20% or less, and exhibited an excellent pollen burst inhibitory effect. In addition, the pollen burst rate was found to be enhanced depending on the concentration of boric acid, and in the presence of boric acid, the effect of suppressing pollen burst was enhanced dependent on the concentration of sodium edetate hydrate. , that in those compositions, the pollen burst inhibitory effect was enhanced by lowering the pH. Furthermore, from these results, in the presence of boric acid and sodium edetate hydrate, polyvinylpyrrolidone K30, which is considered to have an effect of promoting pollen bursting, is less effective than boric acid and sodium edetate hydrate in suppressing pollen bursting. It was suggested to complement or enhance the

(Test example 4)
4. Comparative Test of Intraocular Contamination Between Eye Drop Type Eye Wash and Cup Type Eye Wash The following test was conducted to compare intraocular contamination after eye wash between the case of eye drop type eye wash and the case of cup type eye wash.

1) Preparation of Eye Drops for Washing Eyes (Test Solution) An eye drop for washing eyes (viscosity: 0.84 mPa·s) having the same composition as the eye drop for low-viscosity eye drops 1 in Test Example 1 was used.

2) Test method Two eyes of male Japanese white rabbits were used for the test. The animal was given general anesthesia, and after the hair around the eye was clipped, the skin around the eye was thoroughly rinsed with physiological saline. After the ocular surface was anesthetized and the ocular surface was washed with eye drops for eye wash, the remaining fluid in the conjunctival sac was collected and used as a background sample. After wiping off moisture from the skin around the eye, 2 μL of a 5% fluorescein solution was applied as a contaminant to each of four spots on the skin 5 mm away from the eyelid margin. Then, an eye drop type eye wash was performed by administering 4 drops (46 μL, 4 times) of the eye wash eye drop per eye using a Pipetman. After washing the eyes, the residual fluid in the conjunctival sac was collected and used as a washed sample. Fluorescein concentrations in background and post-wash samples were quantified with a fluorescence plate reader. Contaminant concentration in the conjunctival sac was calculated according to Equation 3 below. Values below the lower limit of quantitative determination were calculated as 0.
[Formula 3]
Contaminant concentration (mg/mL) = fluorescein concentration of post-wash sample (mg/mL) - fluorescein concentration of background sample (mg/mL)

In addition, instead of the eye-drop type eye wash, the same commercially available cup-type eye wash as in Test Example 2 was used, and the cup-type eye washes were performed by contacting the eye surface with 5 mL of the eye wash solution. A test was performed to calculate the contaminant concentration within the conjunctival sac.

3) Test results and discussion The test results are shown in FIG. Here, FIG. 4 is a graph showing the average values of concentrations of contaminants in the conjunctival sac after washing in the cases of eye drop type eye washing and cup type eye washing.

As shown in FIG. 4, the concentration of pollutants in the conjunctival sac after the eye drop type eye wash was about 1/40 of that when the cup type eye wash. Therefore, the eye-drop type eye wash is more effective in preventing and/or avoiding eye troubles caused by contact with the eye periphery and contaminated eye wash medicine entering the eye, compared to the cup type eye wash. shown to be high.

Claims (1)

The invention described herein.

Images