TW201945011A - Eyedrop-type eyewash composition - Google Patents

Abstract

The present invention relates to an eyedrop-type eyewash composition that has a viscosity of 12 mPa.s or less, and that is characterized by being administered at least 4 drops at a time for each eye.

Description

Eye drop type eyewash medicinal composition

The present invention relates to a spot-type eyewash medicinal composition, which is characterized in that it has a viscosity of 12 mPa · s or less and is used by injecting more than 4 drops once per eye.

With the increase in the number of patients with hay fever or the popularity of contact lenses, eye troubles increase. In addition, in order to prevent or treat them, various eye drops have been developed for use. As a method of preventing such troubles that occur in the eyes in advance, the use of eyewash that effectively removes pollen or dust, protein and other dirt entering the eyes is also increasing. As this kind of eyewash, it is generally the following type: after putting the eyewash in the eyewash cup, press the edge of the cup's opening edge against the peripheral part of the user's eye, so that the face and the cup face upward, thereby making the cup The inner eyewash comes into contact with the user's eye surface and blinks several times to perform eyewash (hereinafter this type of eyewash is also called "cup eyewash").

The cup-type eyewash requires about 5 mL of eyewash for one eye wash. When used several times, the amount becomes large and the portability is not good. In addition, since eye wash uses a large amount of about 5 mL of eye wash at a time, there is also a problem of excessive flushing of tears on the surface of the eye, causing problems such as dry eyes. Furthermore, if a cup-type eye washing method is used, there are problems such as the contact between the eye wash and the skin around the eyes, so that the skin moisturizing components around the eyes are rinsed and the skin becomes dry (Patent Document 1). And the dirt (sweat, pollen, dust, etc.) attached to the skin around the eyes will enter the eyes that should be washed and cause eye troubles.

However, there have been few studies related to eyewash methods that have the effect of removing dirt (pollen, dust, protein, etc.) that is close to cup eyewash, equivalent or more, and that solves the above problems that cup eyewash has.
[Prior technical literature]
[Patent Literature]

[Patent Document 1] Japanese Patent Laid-Open No. 2002-003404

[Problems to be solved by the invention]

The object of the present invention is to find a new eye washing method, that is, a composition suitable for eye washing using spotted eyes (hereinafter also referred to as "spotted eye washing") and a usage amount thereof.
[Technical means to solve the problem]

The present inventors have conducted intensive research on eye-washing in the case of eye-type eyewash, and in which usage and dosage, which kind of composition can be used to obtain eye-washing effects similar to or more than cup-type eyewash. As a result, the present inventors have found that when performing eye-washing, the viscosity of the composition and the number of eye drops (drops) per eye (or the total amount of eye drops per eye There is a large correlation between) and eyewash effect. More specifically, it was found that by applying a composition having a viscosity of 12 mPa · s or less to 4 or more drops per eye, preferably 4 or more and 6 or less per eye, a cup-type eyewash, It has the same or better eyewash effect. In addition, it was found that since eye-washing is performed by eye-pointing, the contact between eyewash and skin, eyelashes, etc. around the eyes is minimized, and contamination by contact with skin, eyelashes, etc. around the eyes can be prevented The eyewash that enters into the eyes is troubled by the eyes, thus completing the present invention. Furthermore, the present inventors have also found that a composition obtained by further blending boric acid or a salt thereof and / or edetic acid or a salt thereof into the above composition has an effect of suppressing pollen rupture.

That is, the present invention is as follows.
[1] An eye-type eyewash pharmaceutical composition, which is characterized in that it has a viscosity of 12 mPa · s or less and is used by injecting more than 4 drops per eye at a time.
[2] The ocular eyewash medicinal composition according to [1], characterized in that it is used by injecting 6 drops or less per eye once.
[3] A point-eye type eyewash pharmaceutical composition, characterized in that it has a viscosity of 12 mPa · s or less, and is used by injecting a total amount of eyedrops of more than 120 μL once per eye.
[4] The ophthalmic eyewash pharmaceutical composition according to [3], characterized in that it is used in such a manner that a total eyedrop volume of 300 μL or less is injected once per eye.
[5] The ocular eyewash medicinal composition according to any one of [1] to [4], further comprising a member selected from the group consisting of an anti-inflammatory and astringent component, an antihistamine component, an inorganic salt, and an alkyl polyamine group. At least one of the group consisting of ethyl glycine, boric acid or a salt thereof.
[6] The ocular eyewash pharmaceutical composition according to any one of [1] to [4], further comprising boric acid.
[7] The ocular eye-washing pharmaceutical composition according to any one of [1] to [6], further comprising a viscous agent.
[8] The ocular eyewash pharmaceutical composition according to any one of [1] to [7], further comprising an isotonicity agent, a stabilizer, a pH adjuster, and a dissolving agent.
[9] The dot-eye eyewash pharmaceutical composition according to any one of [1] to [8], which has a pH value of 6.5 or more and 7.0 or less.
[10] The ocular eyewash pharmaceutical composition according to any one of [1] to [9], characterized in that it is used to rinse dirt or foreign matter on the surface of the eye.
[11] The ocular eyewash pharmaceutical composition according to [10], wherein the dirt or foreign matter is pollen, eye secretion or PM2.5.
[12] The ocular eye-washing pharmaceutical composition according to any one of [1] to [11], which is contained in a composition selected from the group consisting of polypropylene, low-density polyethylene, high-density polyethylene, and polyterephthalic acid. Eyelet container formed by at least one of ethylene glycol, polybutylene terephthalate, cyclic olefin polymer and cyclic olefin copolymer.
[13] The ocular eye-washing pharmaceutical composition according to [12], wherein the ocular container is a ocular container capable of spraying liquid.

Furthermore, this invention relates to the following.
[14] An eye-type eyewash method, comprising injecting 4 or more drops of a composition having a viscosity of 12 mPa · s or less once per eye.
[15] The method according to [14], wherein 6 drops or less are administered once per eye.
[16] An eye-type eyewash method, which comprises injecting a composition having a viscosity of 12 mPa · s or less once into each eyedrops with a total eyedrop volume of 120 μL or more.
[17] The method according to [16], in which a total eye volume of 300 μL or less is injected once per eye.
[18] The method according to any one of [14] to [17], wherein the composition further contains a component selected from the group consisting of an anti-inflammatory and astringent component, an anti-histamine component, an inorganic salt, and an alkylpolyaminoethylglycine And at least one member of the group consisting of boric acid or a salt thereof.
[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 thickener.
[21] The method according to any one of [14] to [20], wherein the composition further contains an isotonicity agent, a stabilizer, a pH adjuster, and a dissolving agent.
[22] The method according to any one of [14] to [21], wherein the pH value of the composition is 6.5 or more and 7.0 or less.
[23] The method according to any one of [14] to [22], which is used to rinse dirt or foreign matter on the surface of the eye.
[24] The method according to [23], wherein the dirt or foreign matter is pollen, eye secretion or PM2.5.
[25] The method according to any one of [14] to [24], wherein the composition is contained in a material selected from the group consisting of polypropylene, low density polyethylene, high density polyethylene, polyethylene terephthalate, and poly An eye drop container made of at least one of butylene terephthalate, a cycloolefin polymer, and a cycloolefin copolymer.
[26] The method according to [25], wherein the eye container is an eye container capable of spraying liquid.

Furthermore, this invention relates to the following.
[27] A composition characterized in that it is used for eye-type eyewash, and has a viscosity of 12 mPa · s or less, and is used by injecting more than 4 drops per eye each time.
[28] The composition according to the use according to [27], characterized in that it is used in such a manner that 6 drops or less are administered once per eye.
[29] A composition characterized in that it is used for eye-type eyewash, has a viscosity of less than 12 mPa · s, and is used by injecting a total amount of eyedrops of more than 120 μL once per eye .
[30] The composition according to the use according to [29], characterized in that it is used in such a manner that a total eyedrop volume of 300 μL or less is injected once per eye.
[31] The composition according to any one of [27] to [30], further comprising a compound selected from the group consisting of an anti-inflammatory and astringent component, an anti-histamine component, an inorganic salt, and an alkylpolyaminoethylglycine At least one of the group consisting of an acid and boric acid or a salt thereof.
[32] The composition according to any one of [27] to [30], further comprising boric acid.
[33] The composition for use according to any one of [27] to [32], which further contains a thickener.
[34] The composition according to any one of [27] to [33], further comprising an isotonicity agent, a stabilizer, a pH adjuster, and a dissolving agent.
[35] The composition for the use according to any one of [27] to [34], wherein the pH is 6.5 or more and 7.0 or less.
[36] The composition according to any one of [27] to [35], which is used to rinse dirt or foreign matter on the surface of the eye.
[37] The composition for use according to [36], wherein the dirt or foreign matter is pollen, eye secretion or PM2.5.
[38] The composition according to any one of [27] to [37], which is contained in a composition selected from the group consisting of polypropylene, low density polyethylene, high density polyethylene, polyethylene terephthalate, Eye drop container made of at least one of polybutylene terephthalate, cycloolefin polymer and cycloolefin copolymer.
[39] The composition for the use according to [38], wherein the eye drop container is a eye drop container capable of spraying liquid.

Furthermore, this invention relates to the following.
[40] The use of a composition, which is characterized in that it is used for the manufacture of a composition having a viscosity of 12 mPa · s or less for the manufacture of eye drop eye drops, and the eye drop eye drops is 1 per eye Use 4 or more drops.
[41] The use according to [40], characterized in that the eye drop type eye wash is used in such a manner that 6 drops or less are administered once per eye.
[42] The use of a composition, which is characterized in that it is used for the manufacture of a composition having a viscosity of 12 mPa · s or less for the manufacture of eye drop eye drops, and the eye drop eye drops is 1 per eye It is used by injecting more than 120 μL of total eye drops.
[43] The use according to [42], characterized in that the eye drop type eye wash is used in such a manner that a total eye drop volume of 300 μL or less is injected once per eye.
[44] The use according to any one of [40] to [43], wherein the composition further contains a component selected from the group consisting of an anti-inflammatory and astringent component, an anti-histamine component, an inorganic salt, and an alkylpolyaminoethylglycine And at least one member of the group consisting of boric acid or a salt thereof.
[45] The use according to any one of [40] to [43], wherein the composition further contains boric acid.
[46] The use according to any one of [40] to [45], wherein the composition further contains a thickener.
[47] The use according to any one of [40] to [46], wherein the composition further contains an isotonicity agent, a stabilizer, a pH adjuster, and a dissolving agent.
[48] The use according to any one of [40] to [47], wherein the pH of the composition is 6.5 or more and 7.0 or less.
[49] The use according to any one of [40] to [48], characterized in that an eye drop type eye wash is used to rinse dirt or foreign matter on the surface of the eye.
[50] The use according to [49], wherein the dirt or foreign matter is pollen, eye secretion or PM2.5.
[51] The use according to any one of [40] to [50], wherein the composition is contained in a material selected from the group consisting of polypropylene, low density polyethylene, high density polyethylene, polyethylene terephthalate, and poly An eye drop container made of at least one of butylene terephthalate, a cycloolefin polymer, and a cycloolefin copolymer.
[52] The use according to [51], wherein the eye container is an eye container capable of spraying liquid.

Furthermore, this invention relates to the following.
[53] An eye drop type eye wash, which is characterized in that it has a viscosity of 12 mPa · s or less, and is used by injecting 4 drops or more per eye each time.
[54] The eye drop type eye wash according to [53], characterized in that it is used by injecting 6 drops or less per eye once.
[55] An eye drop type eye wash, which is characterized in that it has a viscosity of 12 mPa · s or less and is used in a manner of injecting a total eye drop amount of 120 μL or more per eye.
[56] The eye drop type eye wash according to [55], characterized in that it is used by injecting a total eye drop amount of 300 μL or less once per eye.
[57] The ophthalmic eye wash according to any one of [53] to [56], further comprising a member selected from the group consisting of an anti-inflammatory and astringent component, an antihistamine component, an inorganic salt, and an alkylpolyaminoethylglycan At least one of the group consisting of amine acid and boric acid or a salt thereof.
[58] The eye drop type eye wash according to any one of [53] to [56], further comprising boric acid.
[59] The dot eye type eye wash according to any one of [53] to [58], further comprising a thickener.
[60] The eye drop type eye wash according to any one of [53] to [59], further comprising an isotonicity agent, a stabilizer, a pH adjuster, and a dissolving agent.
[61] The eye drop type eye wash according to any one of [53] to [60], wherein the pH is 6.5 or more and 7.0 or less.
[62] The dot eye type eye wash according to any one of [53] to [61], which is used for washing dirt or foreign matter on the surface of the eye.
[63] The dot eye type eye wash according to [62], wherein the dirt or foreign matter is pollen, eye secretion or PM2.5.
[64] The ophthalmic eye wash according to any one of [53] to [63], which is contained in a material selected from the group consisting of polypropylene, low density polyethylene, high density polyethylene, and polyethylene terephthalate. Eye drop container made of at least one of polybutylene terephthalate, cycloolefin polymer and cycloolefin copolymer.
[65] The eye drop type eye wash according to [64], wherein the eye drop container is a drop eye container capable of spraying liquid.

Furthermore, the above-mentioned [1] to [65] may be arbitrarily selected in combination or applied.
[Effect of the invention]

By administering a point-type eye-washing medicinal composition having a viscosity of 12 mPa · s or lower to 4 or more drops, preferably 4 to 6 drops or less per eye, a cup-like eye wash, It has the same or better eyewash effect. In addition, compared with the cup-type eyewash, the eye-type eyewash medicinal composition minimizes the contact between the eyewash and the skin, eyelashes, and the like around the eye, and can significantly reduce the dirt (sweat, pollen) attached to the eye area. , Dust, etc.), it can be expected to prevent and / or avoid the troubles caused by the contaminated eyewash that comes into contact with the skin and eyelashes around the eyes. Furthermore, when boric acid or a salt thereof and / or edetic acid or a salt thereof are further added to the eye-point type eyewash pharmaceutical composition, the composition has an effect of suppressing pollen rupture. Therefore, in this case, it is also expected that the pollen can be washed before the pollen ruptures in the eyes and the allergen located inside the pollen is released.

The present invention is described in detail below. In addition, 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 (the same will be used unless otherwise specified).

The viscosity of the composition of the present invention is low viscosity, specifically 12 mPa · s or less, and there is no particular limitation as long as the viscosity is acceptable as an eye drop. More specifically, the upper limit of the viscosity is preferably 10 mPa · s or less, more preferably 5 mPa · s or less, still more preferably 3 mPa · s or less, and even more 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 even more preferably 0.3 mPa · s or more. In addition, the upper limit and the lower limit of the viscosity can be appropriately combined and set as ranges. 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, and still more preferably 0.1 mPa · s or more and 3 mPa · s or less, and particularly preferably It is 0.3 mPa · s or more and 1 mPa · s or less. In addition, in this specification, a low viscosity means the viscosity of 20 mPa * s or less, for example.

The viscosity of the composition of the present invention can be measured by, for example, the viscosity measurement method described in the seventeenth revised edition of the Japanese Pharmacopoeia. Specific measurement methods include a capillary viscometer method and a rotational viscometer method, and the rotational viscometer method is preferred. More specifically, a cone-plate viscometer can be used to measure the viscosity of each formulation at a shear rate of 100 s ^-1 and a temperature of 25.0 ° C. Furthermore, the measurement period of the viscosity of the composition of the present invention is not limited, but it is preferably only as soon as the composition of the present invention is prepared, immediately before the use of the composition of the present invention, or the use period of the composition of the present invention. The measurement may be performed within the (effective period), and more preferably, the measurement may be performed 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 of using the composition of the present invention is not particularly limited as long as it is the number of eye drops (eyewash) sufficient to achieve the desired effect. For example, it is preferably 1 to 6 times / day, and more preferably 3 to 6 times / day. Since the present invention is excellent in portability, it can also be used immediately when it feels a foreign substance in the eyes.

The composition of the present invention preferably has 3 drops or more as the lower limit for each eye, more preferably 4 drops or more for the eye. In addition, the upper limit is not particularly limited. From the viewpoints of patient convenience, eyewash effect, and problems caused by an increase in the amount of eyewash, it is preferable to inject less than 8 drops per eye, more preferably, 6 drops or less. Furthermore, the above upper limit and lower limit can be appropriately combined to form a range. For example, it is preferable to inject 3 or more and 8 or less once per eye, more preferably 4 or more and 8 or less, and even more preferably 4 or more and 6 or less.

In addition, considering that the amount of a single drop of the eye drops is generally 30 to 50 μL, the lower limit of the total eye drop amount of the eye drops once per eye is preferably 90 μL or more, and more preferably 120 μL or more. In addition, the upper limit is not particularly limited. From the viewpoints of patient convenience, eyewash effect, and problems caused by an increase in the amount of eyewash, it is preferably 400 μL or less per eye, and more preferably 300 μL or less. Furthermore, the above upper limit and lower limit can be appropriately combined to form a range. Specifically, for example, as a range of the total ocular fluid volume per eye once, it is preferably 90 μL or more and 400 μL or less, and more preferably 120 μL or more and 300 μL or less.

In the use of the composition of the present invention, the so-called "injecting more than n drops once per eye" means that each eye continuously injects more than n drops during one use. There is no particular limitation on the blinking after the eyes of the composition of the present invention. Specifically, blinking may be performed by dripping one drop per blink, blinking may be performed after dripping a plurality of drops, and blinking may not be performed. Furthermore, from the viewpoint of the eyewash effect, it is preferable to blink 1 or 2 drops per point, and it is more preferable to blink 1 drop per point. In addition, the number of blinks is not particularly limited, and it is preferable to blink 1 to 3 times after each drop or a plurality of drops, and more preferably 1 to 2 times.

The composition of the present invention may contain an appropriate amount of the following ingredients within a range that does not hinder the effects of the present invention, and may be contained without particular limitation as long as it is acceptable as a medicine. The following ingredients are preferably contained as pharmacologically active ingredients (physiologically active ingredients or active ingredients). Specific examples include ε-aminocaproic acid, allantoin, berberine (berberin chloride, berberine sulfate), sodium sulfonate, dipotassium glycyrrhizinate, and zinc (zinc sulfate, zinc lactate). ), Anti-inflammatory and astringent ingredients such as chlorinated lysozyme, antihistamines such as diphenhydramine hydrochloride, clofenamic acid maleate, flavin adenine dinucleotide sodium, cyanocobalamin, retinol Alcohols (retinol acetate, retinyl palmitate), pyridoxine hydrochloride, pantothenates (panthenol, calcium pantothenate, sodium pantothenate), vitamins such as tocopherol acetate, aspartate Class (L-aspartate, L-aspartate, L-aspartate / potassium (equivalent mixture)), aminoethylsulfonic acid (taurine), sodium chondroitin sulfate Other amino acids, such as amino acids, potassium chloride, calcium chloride, sodium chloride, sodium bicarbonate, sodium carbonate, dried sodium carbonate, magnesium sulfate, sodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, alkane Boric acid or a salt thereof, such as polyaminoethylglycine, boric acid, borax, etc., more preferably contains boric acid or a salt thereof, such as boric acid or borax.

The above ingredients can be used alone or in combination of two or more. When these ingredients are contained as pharmacologically active ingredients, their content can be based on the types of pharmacologically active ingredients, the types of other formulated ingredients, and The content, use of the composition, preparation form, and usage method are based on (2) Ophthalmic Drugs described in "Guideline for Separate Volumes of Pharmaceutical Product Manufacturing and Sales Guidelines, Approval Criteria for General Pharmaceutical Product Manufacturing and Sales, and Guidelines for Application Practice". The manufacturing and sales approval standards are set appropriately.

For example, in accordance with the above-mentioned criteria for approval of manufacture and sale of general pharmaceuticals, the composition of the present invention may contain the above-mentioned pharmacologically active ingredient at the maximum concentration (% (w / v)) shown in Table 1.

[Table 1]

When the composition of the present invention contains, for example, the pharmacologically active ingredients of group A shown in Table 1, it is preferable that the composition contains at most three kinds, and further contains at least one of the pharmacologically active ingredients of group B, and contains the group There are at most three kinds of pharmacologically active ingredients. In the case of containing the pharmacologically active ingredient of the B group, it is preferable that the pharmacologically active ingredient contains only one kind, and the pharmacologically active ingredient of the A group contains at most three kinds, and the pharmacologically active ingredient of the C group and the D group contains at least three kinds. When the pharmacologically active ingredient of the E or F group is contained, it is preferable to contain only one kind. Furthermore, when there are subgroups in each group, it is preferable to contain only one kind from the same subgroup.

In the case where boric acid or a salt thereof such as boric acid or borax is contained in the composition of the present invention as a pharmacologically active ingredient (physiologically active ingredient or active ingredient), the content (concentration) is not particularly limited as long as it is acceptable as a medicine . For example, it is preferably 0.01 to 5% (w / v), more preferably 0.1 to 3% (w / v), and even more preferably 0.5 to 1.2% (w / v).

The composition of the present invention may contain an appropriate amount of a pharmacologically active ingredient (physiologically active ingredient or active ingredient) as permitted in medicine in addition to the above-mentioned ingredients within a range that does not prevent the effect of the present invention. Specific examples include epinephrine, epinephrine hydrochloride, ephedrine hydrochloride, tetrahydrozoline hydrochloride, naphthozoline hydrochloride, naphthozoline nitrate, phenylephrine hydrochloride, and dl-methylephedrine hydrochloride. Congestion-removing components (vasoconstriction components) such as collagen, neostigmine methyl sulfate, tropamine, helenien, atropine sulfate and other eye muscle conditioning components (focus adjustment components), zinc sulfate hydrate, Anti-inflammatory and astringent ingredients such as Praprofen, Salicylic acid, Tranexamic acid, Glycyrrhiza uralensis Or its salt (pyrimastast potassium, pirimilast sodium), tranilast, olostatin or its salt (olopatadine hydrochloride), levocabastine or its salt (levacalastine hydrochloride) ), Antihistamines or antiallergic agents such as azalastast, codotetin or its salt (codotetin fumarate), eplestin or its salt (epitestine hydrochloride), vitamin B ₁₂ (hydroxocobalamin, methylcobalamin and adenosyl cobalamin), vitamin B ₆ (pyridoxine, pyridoxal, pyridoxamine), vitamin E (d-α vitamin E acetate), vitamin Su B ₁ (thiamine, thiamine hydrochloride), nicotinic acid (niacin and niacinamide), biotin, folic acid and other vitamins, aspartic acid, glycine, alanine, [gamma] Amino acids such as aminobutyric acid, glutamic acid, arginine, lysine, sulfamethoxazole, sulfamethoxazole sodium, sulfamethoxazole, sulfamethoxazole sodium and other sulfonamides, polyvinyl alcohol, Thickening ingredients such as polyvinylpyrrolidone, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, methyl cellulose, glucose, rifano, cetylpyridinium, benzyl ammonium chloride, benzyl chloride Fungicides such as ammonium, dicloguanidine, polyhexamethylene biguanide, alkyldiaminoethyl glycine hydrochloride, corneal protection such as sodium hyaluronate, and components for treating corneal disorders. Furthermore, the composition of the present invention may not contain sodium hyaluronate in a concentration of 0.075% (w / v) as a pharmacologically active ingredient, and may substantially or completely contain no sodium hyaluronate. Moreover, polyhexamethylene biguanide may not be contained substantially or completely.

The pharmacologically active ingredient (physiologically active ingredient or active ingredient) usable in the composition of the present invention may be used alone or in combination of two or more. Furthermore, the content of the pharmacologically active ingredient can be appropriately set according to the type of the pharmacologically active ingredient, the type and content of other formulated ingredients, the use of the composition, the form of the preparation, the method of use, and the like.

In the composition of the present invention, a thickener, an isotonicity agent, a stabilizer, a pH adjuster, and / or a dissolving agent may be further formulated.

The viscous agent that can be used in the composition of the present invention is not particularly limited as long as it is pharmaceutically acceptable. Examples include polyvinylpyrrolidone K25, polyvinylpyrrolidone K30, polyvinylpyrrolidone K90, and other polyvinylpyrrolidones, methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, and hydroxypropyl Cellulose, hydroxypropyl methyl cellulose 2208, hydroxypropyl methyl cellulose 2906, hydroxypropyl methyl cellulose, carboxymethyl cellulose, carboxyethyl cellulose, nitro cellulose or the like Cellulose derivatives such as salt, polyethylene glycol 300, polyethylene glycol 400, polyethylene glycol 1500, polyethylene glycol 4000, polyethylene glycol 6000 and other polyethylene glycols, dextran 40, dextran Glucans such as 70, sodium hyaluronate (purified sodium hyaluronate, etc.), hyaluronic acid derivatives such as cross-linked hyaluronic acid, alginic acid derivatives such as alginic acid, sodium alginate, polyvinyl alcohol, carboxyvinyl polymer, sodium chondroitin sulfate, Gum arabic, gellan gum, tragacanth, etc., preferably polyvinylpyrrolidone K25, polyvinylpyrrolidone K30, polyvinylpyrrolidone K90 and other polyvinylpyrrolidone, methyl cellulose, ethyl Cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxy Cellulose derivatives such as methylmethyl cellulose 2208, hydroxypropyl methyl cellulose 2906, hydroxypropyl methyl cellulose, carboxymethyl cellulose, carboxyethyl cellulose, nitro cellulose, or salts thereof Hyaluronic acid derivatives such as crosslinked hyaluronic acid, alginic acid derivatives such as alginic acid, sodium alginate, and more preferably polyvinylpyrrolidone K30. Furthermore, the composition of the present invention may be substantially or completely free of sodium hyaluronate (purified sodium hyaluronate, etc.).

The viscous agent usable in the composition of the present invention may be used alone or in combination of two or more. Further, the content of the viscous agent can be appropriately set according to the type of the viscous agent, the kind and content of other formulated ingredients, the use of the composition, the form of the preparation, the method of use, and the like.

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

The isotonic agent that can be used in the composition of the present invention is not particularly limited as long as it is acceptable as a medicine. Examples include potassium salts such as potassium chloride and potassium acetate, calcium salts such as calcium chloride, sodium chloride, sodium bicarbonate, sodium carbonate, dry sodium carbonate, sodium acetate, sodium bisulfite, sodium sulfite, and sodium thiosulfate. Mineral salts such as sodium salt, magnesium sulfate, magnesium chloride and other inorganic salts, glycerol, propylene glycol, polyethylene glycol, mannitol, sorbitol, xylitol, polybutanol and other polyhydric alcohols, etc., preferably potassium chloride , Calcium chloride, calcium chloride, sodium chloride, sodium bicarbonate, sodium carbonate, dry sodium carbonate or magnesium sulfate, more preferably potassium chloride and sodium chloride.

The isotonicity agent which can be used in the composition of the present invention can be used alone or in combination of two or more. Further, the content of the isotonicity agent can be appropriately set according to the type of the isotonicity agent, the type and content of other preparation ingredients, the use of the composition, the form of the preparation, the method of use, and the like.

When an isotonic agent is used in the composition of the present invention, the total content (concentration) of the isotonic agent is, for example, preferably 0.05 to 5% (w / v), and more preferably 0.1 to 1.8% (w / v). , Particularly preferably 0.3 to 0.9% (w / v).

The stabilizer that can be used in the composition of the present invention is not particularly limited as long as it is acceptable as a medicine. Examples include: tromethamine, sodium formaldehyde sulfoxylate (carved white powder), vitamin E, sodium metabisulfite, monoethanolamine, aluminum monostearate, glycerol monostearate, dibutylhydroxytoluene, eddy Acid, sodium edetate, sodium edetate hydrate, polyoxyethylene polyoxypropylene glycol, etc., preferably dibutylhydroxytoluene, edetic acid, sodium edetate or sodium edetate hydrate, and more Preferably it is sodium edetate hydrate.

The stabilizers usable in the composition of the present invention may be used alone or in combination of two or more. Furthermore, the content of the stabilizer can be appropriately set according to the type of the stabilizer, the type and content of other preparation ingredients, the use of the composition, the form of the preparation, 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), more preferably 0.001 to 0.5% (w / v), especially It is preferably 0.005 to 0.1% (w / v).

The pH adjuster that can be used in the composition of the present invention is not particularly limited as long as it is acceptable as a medicine. Examples include dilute hydrochloric acid, acetic acid, sodium hydroxide, sodium bicarbonate, and sodium carbonate. Dilute hydrochloric acid and sodium hydroxide are preferred.

The pH adjuster usable in the composition of the present invention may be used alone or in combination of two or more. Furthermore, the content of the pH adjuster can be appropriately set according to the type of the pH adjuster, the types and contents of other preparation ingredients, the use of the composition, the form of the preparation, the method of use, and the like.

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

The pH value of the composition of the present invention is not particularly limited as long as it is acceptable as medicine, and the upper limit thereof is preferably 7.5 or less, more preferably 7.2 or less, and even more preferably 7.0 or less. The lower limit is preferably 5.0 or more, more preferably 6.0 or more, and even more preferably 6.5 or more. In addition, the upper limit and the lower limit of the pH can be appropriately combined and set as ranges. 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 even more preferably 6.5 or more and 7.0 or less.

The pH value can be measured, for example, according to the pH measurement method described in the seventeenth revised edition of the Japanese Pharmacopoeia.

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 acceptable as a medicine. Examples include water (distilled water, normal water, purified water, sterilized purified water, water for injection, distilled water for injection, etc.), and aqueous dissolving agents such as water-containing ethanol. Water (distilled water, normal water, purified water, and sterilized purified water) is preferred. , Water for injection, distilled water for injection, etc.).

The dissolving agent usable in the composition of the present invention may be used alone or in combination of two or more. Furthermore, the content of the dissolving agent can be appropriately set according to the type of the dissolving agent, the type and content of other preparation ingredients, the use of the composition, the form of the preparation, the method of use, and the like.

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

The composition of the present invention may contain additives other than the above-mentioned additives (thickener, isotonic agent, stabilizer, pH adjuster, dissolving agent) in an appropriate amount within a range that does not prevent the effect of the present invention. The additives other than the above additives are not particularly limited as long as they are acceptable as medicines. For example, a surfactant (co-solvent), a buffer, a preservative, a cooling agent, and the like can be used.

The surfactant (co-solvent) usable in the composition of the present invention is not particularly limited as long as it is acceptable as a medicine. For example, a nonionic surfactant, an amphoteric surfactant, an anionic surfactant, a cationic surfactant, etc. are preferable, and a nonionic surfactant is more preferable.

Examples of the nonionic surfactant include POE (20) sorbitan monolaurate (polysorbate 20), POE (20) sorbitan monopalmitate (polysorbate Ester 40), POE (20) sorbitan monostearate (polysorbate 60), POE (20) sorbitan tristearate (polysorbate 65), POE ( 20) POE sorbitan fatty acid esters such as sorbitan monooleate (polysorbate 80), hydrogenated castor oil (polyoxyethylene hydrogenated castor oil 40) and POE (60) hydrogenated POE castor oil such as castor oil (polyoxyethylene hydrogenated castor oil 60), POE (10) castor oil (polyoxyethylene castor oil 10), POE (35) castor oil (polyoxyethylene castor oil 35), and other POE castor oil , POE alkyl ethers such as POE (9) lauryl ether, POE-POP alkyl ethers such as POE (20) POP (4) cetyl ether, POE (54) POP (39) diol, POE (120) POP (40 ) Diol, POE (160) POP (30) diol, POE (196) POP (67) diol (Poloxamer 407, Pluronic F127), POE (200) POP (70) diol, etc. Polyethylene glycol monostearate such as propylene block copolymer and polyoxyalkylene (40) stearate, etc., preferably POE (20) sorbitan mono-monthly Laurate (polysorbate 20), POE (20) sorbitan monopalmitate (polysorbate 40), POE (20) sorbitan monostearate (polysorbate POE 60), POE (20) sorbitan tristearate (polysorbate 65), POE (20) sorbitan monooleate (polysorbate 80), etc. The sugar anhydride fatty acid ester is more preferably POE (20) sorbitan monooleate (polysorbate 80).

Examples of the amphoteric surfactant include N- [2-[[2- (alkylamino) ethyl] amino] ethyl] glycine and its salts.

Examples of the anionic surfactant include alkylbenzenesulfonate, alkylsulfate, polyoxyethylene alkylsulfate, α-sulfo fatty acid ester salt, and α-olefinsulfonic acid.

Examples of the cationic surfactant include benzyl ammonium chloride, benzethonium chloride, and dichlorophenformin gluconate.

These surfactants can be used singly or in combination of two or more. Further, the content of the surfactant can be appropriately set according to the type of the surfactant, the type and content of other preparation ingredients, the use of the composition, the form of the preparation, 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), and more preferably 0.01 to 1% (w / v). , More preferably 0.05 to 0.5% (w / v).

The buffering agent that can be used in the composition of the present invention is not particularly limited as long as it is acceptable as a medicine. Examples include boric acid, sodium borate, potassium tetraborate, potassium metaborate, boric acid such as ammonium borate, borax, or a salt thereof, phosphoric acid, disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, trisodium phosphate, and triphosphate Phosphoric acid or its salt such as potassium, calcium monohydrogen phosphate, calcium dihydrogen phosphate, carbonic acid, sodium bicarbonate, sodium carbonate, ammonium carbonate, potassium carbonate, calcium carbonate, potassium bicarbonate, magnesium carbonate or its salt, citric acid, Citric acid or its salt such as sodium citrate, potassium citrate, calcium citrate, sodium dihydrogen citrate, disodium citrate, acetic acid, ammonium acetate, potassium acetate, acetic acid such as calcium acetate, sodium acetate, or asparagus Aspartic acid or its salt, such as amino acid, sodium aspartate, magnesium aspartate, potassium aspartate, ethylenediaminediacetic acid (EDDA), ethylenediaminetriacetic acid, ethylenediaminetetraacetic acid ( (Edetic acid, EDTA), ethylenediamine tetraacetic acid disodium hydrate (sodium edetate hydrate), N- (2-hydroxyethyl) ethylenediaminetriacetic acid (HEDTA), diethylene triaminepenta Ethylene diamine acetic acids such as acetic acid (DTPA) or their salts, amino acids such as ε-aminohexanoic acid, etc., preferably boric acid, sodium borate, potassium tetraborate, metaboron Boric acids such as potassium, ammonium borate, borax or their salts, phosphoric acid such as phosphoric acid, disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, trisodium phosphate, tripotassium phosphate, calcium monohydrogen phosphate, calcium dihydrogen phosphate or the like Amino acids such as salts and ε-aminohexanoic acid are more preferably boric acid, borax, or ε-aminohexanoic acid.

The buffering agents usable in the composition of the present invention may be used alone or in combination of two or more. Furthermore, the content of the buffering agent can be appropriately set according to the type of the buffering agent, the type and content of other preparation ingredients, the use of the composition, the form of the preparation, 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 to 5% (w / v), more preferably 0.005 to 3% (w / v), especially It is preferably 0.01 to 2% (w / v).

The preservative that can be used in the composition of the present invention is not particularly limited as long as it is acceptable as a medicine. Examples include biguanide compounds such as polyhexamethylene biguanide, polyhexanide hydrochloride, zinc chloride, alkyldiaminoethylglycine, sodium benzoate, ethanol, benzyl ammonium chloride, and benzethonium chloride. Ammonium, dichlorophenformin hexane, chlorobutanol, sorbic acid, potassium sorbate, sodium dehydroacetate, methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, parahydroxy Butyl benzoate, hydroxyquinoline sulfate, phenylethanol, benzyl alcohol, Glokill (manufactured by Rhodia, trade name), boric acid, borax, chlorite, etc., preferably benzyl ammonium chloride, dichlorophenformate gluconate Hexane, sorbic acid, phenethyl alcohol, boric acid, borax, chlorous acid, more preferably benzyl ammonium chloride, dichlorophenformin hexane, phenethyl alcohol, boric acid, borax, chlorite. Furthermore, the composition of the present invention may be substantially or completely free of polyhexamethylene biguanide.

The preservatives usable in the composition of the present invention may be used alone or in combination of two or more. Furthermore, the content of the preservative can be appropriately set according to the type of the preservative, the type and content of other formulated ingredients, the use of the composition, the form of the preparation, 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), more preferably 0.0005 to 0.5% (w / v), and further It is preferably 0.001 to 0.2% (w / v), and particularly preferably does not substantially or completely contain a preservative, especially benzyl ammonium or a salt thereof, or methyl parahydroxybenzoate, ethyl parahydroxybenzoate, A composition of parabens such as propyl hydroxybenzoate, butyl parahydroxybenzoate, or a salt thereof.

The cooling agent usable in the composition of the present invention is not particularly limited as long as it is acceptable as a medicine. Examples include eucalyptus oil, citrus oil, peppermint oil, fennel oil, rose oil, cinnamon oil, green peppermint oil, camphor oil, cool mint, and mint oil containing terpenoids, menthol, Terpenoids such as menthol, camphor, borneol, geraniol, nerol, eucalyptus, citronellol, ecdysone, anisinol, eugenol, tincture, linalool, linal acetate, etc. Menthol, camphor, borneol and geraniol, more preferably menthol and borneol. The terpenoid may be any of the d-body, the l-body, and the dl-body, and examples thereof include l-menthol, d-menthol, dl-menthol, dl-camphor, d-camphor, dl-borneol, d-borneol and the like are preferably l-menthol, dl-camphor, d-camphor and d-borneol.

The cooling agent usable in the composition of the present invention may be used alone or in combination of two or more. Further, the content of the cooling agent can be appropriately set according to the type of the cooling agent, the type and content of other formulated ingredients, the use of the composition, the form of the preparation, 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 0.1% (w / v), especially It is preferably 0.005 to 0.05% (w / v).

When the composition of the present invention contains boric acid or a salt thereof and / or edetic acid or a salt thereof in the above-mentioned ingredients, and if it contains polyvinylpyrrolidone as appropriate, it has the effect of suppressing pollen rupture, so it is preferable.

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 is more preferably 0.2 to 2, more preferably 0.7 to 1.5, and even more preferably 1.0 to 1.2.

Furthermore, the osmotic pressure ratio is based on the seventeenth revised edition of the Japanese Pharmacopoeia, and the ratio of the osmotic pressure of the sample to the 286 mOsm (the osmotic pressure of the 0.9% (w / v) sodium chloride aqueous solution) is set. The osmotic pressure can be referred to Japan. It is measured by the osmotic pressure measurement method (freezing point reduction method) described in the Pharmacopoeia. For the standard solution (0.9% (w / v) sodium chloride aqueous solution) for measuring the osmotic pressure ratio, sodium chloride (Japanese Pharmacopoeia Standard Reagent) can be used. ) After drying at 500 to 650 ° C for 40 to 50 minutes, place it in a desiccator (silicone) to cool, accurately weigh 0.900 g, dissolve it in purified water, and accurately prepare 100 mL, or use a commercially available osmotic pressure ratio Standard solution for measurement (0.9% (w / v) aqueous sodium chloride solution).

The composition of the present invention can be provided in any container (main body, middle plug, lid). The container containing the composition is not particularly limited as long as it is acceptable as a medicine. Examples include glass containers and polypropylene, low density polyethylene, high density polyethylene, polyethylene terephthalate, polybutylene terephthalate, cycloolefin polymers, cycloolefin copolymers, Polyacrylate, polyethylene naphthalate, polycarbonate, polytetrafluoroethylene, polyimide, polymethylpentene, copolymers of these monomers, and combinations of these materials More than one kind of plastic container, preferably polypropylene, low density polyethylene, high density polyethylene, polyethylene terephthalate, polybutylene terephthalate, cyclic olefin polymer and cyclic olefin copolymerization Materials, copolymers of these monomers, and a combination of two or more plastic containers made of these materials. In addition, the so-called combination here may mix different materials, or may use different materials as a layer structure. Furthermore, the above-mentioned container may be a multi-dose form container that can be used repeatedly, or a unit-dose form that is used only once, and is preferably a multi-dose form container that can splash liquid and can be used repeatedly. In addition, the container containing the composition of the present invention is, for example, a general eye drop container, but as described above, the eye drop container is usually designed in such a manner that one drop volume becomes 30 to 50 μL.

The composition of the present invention is used for rinsing dirt or foreign matter on the surface of the eye, for example. In the present invention, "rinsing dirt or foreign matter" means washing dirt or foreign matter on the surface of the eye from the eye to the outside of the eye.

In the present invention, the so-called "dirt or foreign matter" is not particularly limited as long as it is a substance that causes discomfort to the eyes. For example, pollen such as cedar, hinoki, and gramineous plants, dust such as room dust, eye secretions such as protein, skin secretions such as sweat, cosmetics such as PM2.5, eye shadow, mascara, and pressed powder, etc. It is pollen and PM2.5 of cedar, cedar, grass, etc.

The composition of the present invention can be used, for example, as a composition for contact lenses, and can be applied to all commercially available contact lenses including hard contact lenses and / or soft contact lenses. Use on the eye surface). The soft contact lenses herein include, for example, both ionic and non-ionic lenses, and include both polysiloxane hydrogel contact lenses and non-polysiloxane hydrogel contact lenses. In addition, all soft contact lenses classified into groups I to IV are included.

The composition of the present invention can be expressed as "useable when wearing contact lenses (hard contact lenses and soft contact lenses)", "use when contact lenses (hard contact lenses and soft contact lenses) are worn", and so on. Similar expressions can be made. In addition, the display can be performed directly or indirectly. As examples of the direct display, the descriptions on the packaging of the product itself, the package, the container, the label, and the tag can be cited as examples of the indirect display. Examples include advertisements, promotions, and explanations for physicians through transaction documents, operating instructions, accompanying documents, catalogs, websites, stores, exhibitions, kanbans, bulletin boards, newspapers, magazines, televisions, radios, and emails. And other activities.

The detailed description of the composition and the like of the present invention described above is also applicable to the following aspects of the present invention.

One aspect of the present invention is an eye-type eyewash method, which comprises injecting 4 or more drops of a composition having a viscosity of 12 mPa · s or less once per eye.

One aspect of the present invention is a composition, which is characterized in that it is used for eye-type eyewash, has a viscosity of 12 mPa · s or less, and is used by injecting more than 4 drops per eye.

One aspect of the present invention is the use of a composition, which is characterized in that it is used for the manufacture of a composition with a viscosity of 12 mPa · s or less for the manufacture of eye drop eye drops, and the eye drop eye drops Use 4 or more drops per eye.

One aspect of the present invention is an eye drop type eye wash, which is characterized in that it has a viscosity of 12 mPa · s or less, and is used by injecting more than 4 drops per eye.
[Example]

<Formulation example>
Examples of the preparations of the present invention are shown in Table 2 below, but these are for better understanding of the present inventors, and do not limit the scope of the present invention at all. In addition, in the following formulation examples, the amount of each component is the content in 100 mL of the formulation, and their viscosity is 12 mPa · s or less.

[Table 2]

Furthermore, the pharmacologically active ingredients, types of additives, blending amounts, and viscosities in Formulation Examples 1 to 6 can be appropriately adjusted to obtain a desired composition having a viscosity of 12 mPa · s or less.

<Example>
Hereinafter, it will be shown as an example 1. A test on the correlation between the viscosity of eye drops for eyewash and the cleaning effect, 2. A test on the number of drops per eye and the cleaning effect, and a test on the effect of pollen cracking suppression 4. Confirmation test of intraocular contamination of eye-type eyewash and cup-type eyewash. However, these test examples are for better understanding of the present inventors, and do not limit the scope of the present invention in any way.

(Test example 1)
1. Correlation test of the viscosity and washing effect of eye drops for eye wash The following test is performed to investigate the viscosity of eye drops for eye wash (eye drop eye drops) and the cleaning effect relationship.

1) Preparation of eyewash eye drops (test solution) First, 8700 mL of water is heated to 50 ° C, and added to 100.0 g of boric acid, 50.0 g of polyvinylpyrrolidone K30, 1.0 g of sodium edetate hydrate, Stir in 40.0 g of sodium chloride and 10.0 g of potassium chloride, cool them to room temperature, add dilute hydrochloric acid / sodium hydroxide to adjust the pH to 6.7, and add water to the total amount to 10,000 mL. Preparation of low viscosity eye drops 1 for eyewash. At this time, the viscosity of the low viscosity eye drops 1 was 0.84 mPa · s. Next, 3.0 g of dispersed hydroxymethylcellulose (HEC) was added to 1 150 mL of low-viscosity eye drops, heated to 70 ° C, stirred and dissolved to prepare a high viscosity for viscosity adjustment. Eye drops. Then, combine 6 mL of eye drops for viscosity adjustment and 1 34 mL of eye drops for low viscosity eye wash, and stir well to prepare low eye drops 2 for eye viscosity 2 with a viscosity of 11.56 mPa · s, and combine them for viscosity adjustment. Eye drops 12 mL and low viscosity eye wash eye drops 1 28 mL and thoroughly stirred to prepare a high viscosity eye wash eye drops 1 with a viscosity of 56.4 mPa · s, combined with viscosity adjustment eye drops 20 mL and low Viscosity eye wash eye drops 1 20 mL and stir well to prepare a high viscosity eye wash eye drops 2 with a viscosity of 194.2 mPa · s. In addition, the viscosity was measured based on the seventeenth revised edition of the Japanese Pharmacopoeia using a cone-plate viscometer at a shear rate of 100 s ^-1 and a measurement temperature of 25.0 ° C. immediately before the test was performed. Table 3 shows the viscosity of the eye drops for each eye wash.

[table 3]

2) Test method Male Japanese white rabbits were used in the cleaning effect test. The subjects were two eyes of one horse and two eyes. The animals were subjected to general anesthesia and ocular surface anesthesia. A solution (3% suspension) of spherical fluorescent beads having an average diameter of about 40 μm was uniformly suspended, and 1% suspension of spherical fluorescent beads manufactured by Spherotech Inc. (Concentrated)) 50 μL of each eye. Thereafter, the eye drops for eye-washing were administered to the eye drops in an amount of 4 drops per eye (4 times 46 μL) using a pipette, thereby washing the surface of the eyes by eye-washing. After washing, use a pipette to recover the fluorescent beads remaining on the eye surface. The volume of the recovered fluorescent bead-containing solution (x μL) was measured with a pipette. A part of the recovered solution was placed in a Fuchs-Rosenthal hemocytometer, and the bead density (y pieces / μL) was measured by an optical microscope according to the usage of the hemocytometer. According to the formula (x × y), calculate the number of recovered fluorescent beads (number) from the volume of the recovered solution (x μL) and the density of the beads (y number / μL), and set it as the residual beads after eye washing Number (b). Moreover, the eyedrops for eyewash were not directly administered to the eye, and the recovery operation was performed directly, and the number of recovered fluorescent beads was similarly calculated. Let this be the number of remaining beads (a) which were not wash | cleaned. The residual rate of beads after eye-washing with each eye-wash eye drops was calculated according to the following formula 1. Here, a low bead residual rate means a high cleaning effect. In addition, the residual rate of the beads which had not been washed was set to 100%.
[Formula 1]
Bead Residual Ratio (%) = {Number of Remaining Beads After Eye Washing (b) / Number of Remaining Beads Without Washing (a)} × 100

3) Test results and discussion The test results are shown in Table 4 and Figure 1. Here, FIG. 1 is a graph in which the horizontal axis is the viscosity (mPa · s) of eye drops and the vertical axis is the bead residual rate (%).

[Table 4]

As shown in Table 4 and Figure 1, the cleaning effect of the low-viscosity eye drops 1 (0.84 mPa · s) and the low-viscosity eye drops 2 (11.56 mPa · s) (expressed as the bead residue rate) Excellent, 15% or less. Among them, the low-viscosity eye drops 1 (0.84 mPa · s) has excellent cleaning effect, and the bead residue rate is 3.0%. In addition, the bead residue rate of eye drops 1 (56.4 mPa · s) for high-viscosity eye wash increased from the bead residue rate (14.7%) of eye drops 2 (11.56 mPa · s) for low-viscosity eye drops to 39.6%. . From the above, it has been shown that if the viscosity of the eye drops for eyewash exceeds about 12 mPa · s, the cleaning effect decreases sharply.

(Test Example 2)
2. Tests related to the number of eye drops and cleaning effect once per eye Perform the following tests to investigate the case of eye wash once per eye (eye drop eyewash) The relationship between the number of eye drops and its cleaning effect.

1) Preparation of eye wash eye drops (test solution) Eye wash eye drops (viscosity 0.84 mPa · s) having the same composition as the low viscosity eye wash eye drops 1 in Test Example 1 were used.

2) Test method The test subjects were two eyes of two male Japanese white rabbits and four eyes. Use a pipette to administer eye drops for 2, 4, 6, and 8 drops (46 μL of 2, 4, 6, and 8 times) to each eye for eye-type eyewash Except for this, a test was performed in the same manner as in Test Example 1 to calculate the bead residual rate after eyewash at the number of eye drops at each point. In addition, as a reference example, instead of the eye-type eyewash, an eyewash cup attached to a commercially available cup-type eyewash (manufactured by Lotton Pharmaceuticals) was used to contact 5 mL of eye-wash eyedrops with the surface of an animal's eye to perform a cup Except for the eyewash method, a test was performed in the same manner to calculate the bead residual rate.

3) Test results and discussion The test results are shown in Table 5 and Figure 2. Here, FIG. 2 is a graph showing the relationship between the amount of eye drops for each eye wash (the number of eye drops per eye, cup eye wash as a reference example) and the bead residue rate (%). In addition, the residual rate of the beads which had not been washed was set to 100%.

[table 5]

As shown in Table 5 and FIG. 2, when eye drops for eye-washing were dripped with 4 or more drops per eye at one time for eye-washing, the bead residue rate was 2% or less, showing excellent cleaning effect. In addition, the eye-type eye-washing effect of 4 or more drops per eye once is superior to the cup-type eye-washing using a conventional eye-washing cup. According to the above, it has been shown that by performing eye drop eyewash with 4 or more drops per eye drop for eyewash eye drops, a sufficient effect of removing foreign matter on the eye surface can be achieved.

(Test Example 3)
3. Pollen rupture suppression effect test
3-1. Pollen rupture suppression effect of various ingredients The following tests were performed to investigate the pollen rupture suppression effect of various ingredients.

1) Preparation of test solution 12.5 g of disodium hydrogen phosphate hydrate was added to 900 mL of water, stirred and dissolved. Water was added to a total amount of 1,000 mL, and the resulting solution was set to 1.25 times solution 1. Take 1 40 mL of 1.25 times solution, add dilute hydrochloric acid / sodium hydroxide to adjust the pH to 7.0, and add water to make a total of 50 mL as test solution 1. 0.05 g of potassium chloride was added to 1 40 mL of the 1.25-fold solution, stirred and dissolved. To this solution, dilute hydrochloric acid / sodium hydroxide was added to adjust the pH to 7.0, and water was added to make a total of 50 mL as Test Solution 2. 0.2 g of sodium chloride was added to 1 40 mL of the 1.25-fold solution, stirred and dissolved. Dilute hydrochloric acid / sodium hydroxide was added to this solution to adjust the pH value to 7.0, and water was added to make a total of 50 mL as test solution 3. 0.5 g of boric acid was added to 1 40 mL of a 1.25-fold solution, stirred and dissolved. Dilute hydrochloric acid / sodium hydroxide was added to this solution to adjust the pH to 7.0, and water was added to make a total of 50 mL as test solution 4. Add 0.05 g of sodium edetate hydrate to 1 40 mL of 1.25-fold solution, stir and dissolve. Dilute hydrochloric acid / sodium hydroxide was added to this solution to adjust the pH value to 7.0, and water was added to make a total of 50 mL as test solution 5. 0.25 g of polyvinylpyrrolidone K30 was added to 1 40 mL of a 1.25-fold solution, stirred and dissolved. Dilute hydrochloric acid / sodium hydroxide was added to this solution to adjust the pH to 7.0, and water was added to make a total of 50 mL as test solution 6. Table 6 shows the composition of the aqueous solutions of the test solutions 1 to 6. Here, disodium hydrogen phosphate hydrate is contained as a pH buffering agent. The viscosity of the test liquids 1 to 6 was 12 mPa · s or less.

[TABLE 6]

2) Test method About 50 μL of each test solution was added dropwise to about 3 μL of cedar pollen particles. The ruptured and unruptured liquid cells were measured under an optical microscope for 5 minutes. The pollen rupture rate was calculated according to the following Equation 2.
[Formula 2]
Pollen rupture rate (%) = {Number of ruptured liquid cells / (Number of ruptured liquid cells + Number of unruptured liquid cells)} × 100

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

3-2. Pollen rupture suppression effect of various compositions The following tests were performed to investigate the pollen rupture suppression 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 solution was cooled to room temperature, water was added to make a total amount of 200 mL, and the resulting solution was set to 1.25 times solution 2. Take 2 40 mL of 1.25 times solution, add dilute hydrochloric acid / sodium hydroxide to adjust the pH to 7.2, and add water to make a total of 50 mL as test solution 7. The 1.25 times solution 2 40 mL was heated to 45 ° C, and 0.40 g of boric acid was added and stirred. After the solution was cooled to room temperature, dilute hydrochloric acid / sodium hydroxide was added to adjust the pH to 7.2, and water was added to make a total amount of 50 mL as test solution 8. The 1.25 times solution 2 40 mL was heated to 45 ° C., and 0.025 g of sodium edetate hydrate was added and stirred. After the solution was cooled to room temperature, dilute hydrochloric acid / sodium hydroxide was added to adjust the pH to 7.2, and water was added to make a total amount of 50 mL as test solution 9. The 1.25-fold solution 2 40 mL was heated to 45 ° C, and 0.05 g of sodium edetate hydrate was added and stirred. After the solution was cooled to room temperature, dilute hydrochloric acid / sodium hydroxide was added to adjust the pH to 7.2, and water was added to make a total amount of 50 mL as test solution 10. To 800 mL of water, 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 and stirred. Water was added to this solution to make a total of 960 mL, and the resulting solution was set to 1.25 times solution 3. Take 3 320 mL of 1.25 times solution, add dilute hydrochloric acid / sodium hydroxide to adjust the pH to 7.0, and add water to make a total of 400 mL as test solution 11. Take 3 320 mL of 1.25 times solution, add dilute hydrochloric acid / sodium hydroxide to adjust the pH to 6.5, and add water to make a total of 400 mL as test solution 12. The composition of the aqueous solution of the test liquids 7-12 is shown in Table 7. The viscosity of the test solutions 7 to 12 is 12 mPa · s or less.

[TABLE 7]

2) Test method The test was performed by the method described in "3-1. Pollen rupture 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 rupture rate of each test solution. Here, the pollen rupture rate of the test liquids 7 to 12 was 20% or less, which showed an excellent pollen rupture suppression effect. In addition, it is shown that the pollen rupture rate depends on the concentration of boric acid to enhance the pollen rupture suppression effect, and in the presence of boric acid depends on the concentration of sodium edetate hydrate to enhance the pollen rupture suppression effect. Moreover, these compositions are lowered due to the decrease in pH And the pollen rupture suppression effect is enhanced. Furthermore, based on these results, it was suggested that polyvinylpyrrolidone K30, which is considered to have a pollen rupture promoting effect, in the presence of boric acid and sodium edetate hydrate filled or enhanced the pollen rupture suppression of boric acid and sodium edetate hydrate effect.

(Test Example 4)
4. Comparison test of intraocular pollution of eye-type eyewash and cup-type eyewash The following test was performed to compare the intra-eye pollution of eye-type eyewash and cup-type eyewash after eyewash.

1) Preparation of eye wash eye drops (test solution) Eye wash eye drops (viscosity 0.84 mPa · s) having the same composition as the low viscosity eye wash eye drops 1 in Test Example 1 were used.

2) Test method Two eyes of a male Japanese white breed rabbit were used in the test. The animals were subjected to general anesthesia, the hair around the eyes was cut off, and the skin around the eyes was thoroughly washed with physiological saline solution. After ocular surface anesthesia, the eye surface was washed with eye drops for eye washing, and then the residual liquid in the conjunctival sac was taken as a background sample. After wiping off the moisture around the skin around the eyes, apply 2 μL of a 5% luciferin solution as a contaminating substance to 4 places on the skin 5 mm from the edge of the eyelid. Then, an eye-washing eyedrop was administered to the eye-dropping solution in an amount of 4 drops per eye (4 times 46 μL) using a pipette, thereby performing eye-washing. After the eye washing operation, the residual liquid in the conjunctival sac was taken as a washed sample. Fluorescence plate reader was used to quantify the luciferin concentration in the background sample and the washed sample. The contamination substance concentration in the conjunctival sac was calculated according to the following Equation 3. It should be noted that a value that does not reach the lower limit of the calculation is calculated as 0.
[Formula 3]
Contaminant concentration (mg / mL) = luciferin concentration (mg / mL) of the washed sample-luciferin concentration (mg / mL) of the background sample

In addition, instead of eye-type eyewash, a cup of the same commercially available eyewash as in Test Example 2 was used, and 5 mL of eye-wash eyedrops were brought into contact with the surface of the eye to perform cup-type eyewash. The test was performed in the same manner to calculate the concentration of pollutants in the conjunctival sac.

3) Test results and discussion The test results are shown in FIG. 4. Here, FIG. 4 is a graph showing the average value of the concentration of the pollutants in the conjunctival sac after washing in the case of spot-eye washing and cup-washing.

As shown in FIG. 4, the concentration of pollutants in the conjunctival sac during eye-washing is about 1/40 of that in cup-washing. Therefore, compared with the cup-type eyewash, the spot-type eyewash is more effective in preventing and / or avoiding the eye trouble caused by the contact with the eye peripherals during eyewashing and contamination of the eyewash entering the eyes.

FIG. 1 is a graph showing the relationship between the viscosity of eye drops for eye wash and its cleaning effect.

FIG. 2 is a graph showing the relationship between the number of eye drops of eye drops for eye wash once per eye and its cleaning effect.

Fig. 3A is a graph showing the effect of suppressing pollen rupture of various ingredients.

Fig. 3B is a graph showing the effect of suppressing pollen rupture in an aqueous solution containing various components.

FIG. 4 is a graph showing the results of eye contamination after eye-washing in the case of spot-type eyewashing and cup-type eyewashing.

Claims (13)

An ophthalmic eyewash pharmaceutical composition, which is characterized in that it has a viscosity of 12 mPa · s or less and is used by injecting 4 drops or more per eye each time. The point-type eyewash pharmaceutical composition according to claim 1, which is used in such a manner that 6 drops or less are administered once per eye. An ophthalmic eyewash pharmaceutical composition is characterized in that it has a viscosity of 12 mPa · s or less and is used by injecting a total eyedrop volume of 120 μL or more per eye per time. For example, the ophthalmic eyewash pharmaceutical composition according to claim 3 is used by injecting a total eyedrop volume of 300 μL or less once per eye. The ophthalmic eyewash pharmaceutical composition according to any one of claims 1 to 4, further comprising a compound selected from the group consisting of an anti-inflammatory and astringent component, an antihistamine component, an inorganic salt, an alkyl polyaminoethyl glycine, and At least one member of the group consisting of boric acid or a salt thereof. The ocular eye-washing pharmaceutical composition according to any one of claims 1 to 4, further comprising boric acid. The ophthalmic eyewash pharmaceutical composition according to any one of claims 1 to 6, further comprising a viscous agent. The ocular eyewash pharmaceutical composition according to any one of claims 1 to 7, further comprising an isotonicity agent, a stabilizer, a pH adjuster, and a dissolving agent. The ophthalmic eyewash pharmaceutical composition according to any one of claims 1 to 8, which has a pH value of 6.5 or more and 7.0 or less. The point-type eyewash pharmaceutical composition according to any one of claims 1 to 9, which is used to rinse dirt or foreign matter on the surface of the eye. The point-type eyewash pharmaceutical composition according to claim 10, wherein the dirt or foreign matter is pollen, eye secretion or PM2.5. The ophthalmic eye-washing pharmaceutical composition according to any one of claims 1 to 11, which is contained in a composition selected from the group consisting of polypropylene, low density polyethylene, high density polyethylene, polyethylene terephthalate, and polyethylene terephthalate. An eye drop container made of at least one of butyl phthalate, a cycloolefin polymer, and a cycloolefin copolymer. The ocular eyewash pharmaceutical composition according to claim 12, wherein the ocular container is an ocular container capable of spraying liquid.