JP7303792B2 - Pollen burst suppressing composition - Google Patents

Description

The present invention relates to a composition for suppressing pollen bursting and a method for suppressing pollen bursting, which contains at least one selected from the group consisting of boric acid or its salts, edetic acid or its salts, and chlorhexidine or its salts as an active ingredient.

Hay fever is an allergic disease caused by pollen of Japanese cedar, Japanese cypress, etc. In particular, when pollen enters the eyes, it causes unpleasant symptoms such as itchy eyes continuously for a long period of time. In addition, the prevalence of hay fever tends to increase every year, which has become a social problem in recent years.

The onset mechanism of hay fever has been elucidated by previous studies. Specifically, when pollen of cedar, Japanese cypress, or the like adheres to the mucous membrane of the eyes or nose, the outer shell of the pollen bursts and antigen proteins (allergen substances) are released and enter the mucous membrane. When antigenic proteins enter the mucosa, specific IgE antibodies are produced and sensitized by binding to receptors on mucosal mast cells. In this state, when the antigen protein is exposed again, chemical mediators such as histamine are released from mast cells due to antigen-antibody reactions, and these substances bind to receptors, causing allergic symptoms such as itching. be Therefore, avoiding contact with pollen is the most effective way to prevent hay fever, but it is difficult to completely avoid contact with pollen in daily life. Pollen may also be ruptured when it comes into contact with a composition such as an eye wash or an eye drop. Therefore, if it is possible to suppress the rupture of the outer shell of the pollen even if it comes into contact with the pollen, or if the pollen can be washed away before the outer husk of the pollen ruptures, it will lead to the prevention of hay fever, which is very useful.

Various methods for suppressing pollen bursting are known, for example, Patent Document 1 discloses a water-soluble compound having an alkylene moiety having 3 to 18 carbon atoms in the molecule and a part of the hydrogen atoms of the alkylene moiety or Contains one or more compounds selected from water-soluble compounds which are all substituted with one or more of hydroxyl groups, carboxyl groups, carboxyester groups, formyl groups, amide groups, amino groups, alkylamino groups and alkoxyl groups In addition, the nasal cleansing effect of a composition having a pH of 3 to 8 and a viscosity of 1.3 cP or less at 25°C is disclosed. Further, in Patent Document 2, the surface of anionic silica fine particles is coated with alumina and contains one or more fine particles selected from the group consisting of silica fine particles and alumina fine particles. Inhibitor compositions are disclosed. Furthermore, in Patent Document 3, at least two of the four components of glycyrrhizic acid and/or its salts, chondroitin sulfate and/or its salts, chlorpheniramine and/or its salts, ε-aminocaproic acid and/or its salts A composition applied to textile products, indoor spaces, etc., which suppresses pollen burst by combining two components is disclosed.

However, in Patent Documents 1 to 3, the compositions described in Patent Documents 1 to 3 contain boric acid or its salts, edetic acid or its salts, and chlorhexidine or its salts as active ingredients to suppress pollen bursting. It is neither described nor suggested to do so.

JP-A-2000-109425 JP 2006-008943 A JP 2018-002640 A

An object of the present invention is to provide a composition for suppressing pollen bursting and a method for suppressing pollen bursting that can be incorporated as a pharmaceutically acceptable active ingredient.

The present inventors have earnestly studied what kind of ingredients a composition containing as an active ingredient has an effect of suppressing pollen bursting. As a result, it was found that a composition containing at least one selected from the group consisting of boric acid or its salts, edetic acid or its salts, and chlorhexidine or its salts as an active ingredient has an excellent pollen burst inhibitory effect. I completed the present invention.

That is, the present invention is as follows.
[1] A composition for inhibiting pollen bursting containing, as an active ingredient, at least one selected from the group consisting of boric acid or its salts, edetic acid or its salts, and chlorhexidine or its salts.
[2] The composition according to [1], which contains boric acid or a salt thereof as an active ingredient.
[3] The composition according to [1] or [2], wherein the boric acid or its salt is boric acid or borax.
[4] The composition according to [2], which further contains edetic acid or a salt thereof.
[5] The composition according to [1] or [4], wherein the edetic acid or its salt is sodium edetate hydrate.
[6] The composition according to any one of [1] to [5], further containing polyvinylpyrrolidone.
[7] The composition according to any one of [1] to [6], which has a pH of 7.0 or less.
[8] The composition according to [7], which has a pH of 6.5 or more and 7.0 or less.
[9] The composition according to any one of [1] to [8], further containing at least one selected from the group consisting of tonicity agents, stabilizers, thickeners, pH adjusters and solubilizers. thing.
[10] The composition according to [9], which has an osmotic pressure ratio of 1.0 to 1.2.
[11] The composition according to any one of [1] to [10], which is an ophthalmic composition.
[12] An ophthalmic composition comprising only boric acid or its salts, edetic acid or its salts, sodium chloride, potassium chloride, polyvinylpyrrolidone, dilute hydrochloric acid, sodium hydroxide and purified water, and having a pH of 6.5 to 7.0. 0 and an osmotic pressure ratio of 1.0 to 1.2.
[13] The ophthalmic composition of [11] or [12], which is an eye wash or eye drops.
[14] The ophthalmic composition of [13], wherein the eye wash is an eye drop type eye wash.
[15] A method for suppressing pollen bursting, comprising contacting pollen with a composition containing at least one selected from the group consisting of boric acid or its salts, edetic acid or its salts, and chlorhexidine or its salts. A method consisting of:

The invention also relates to:
[16] A pollen burst inhibitor containing, as an active ingredient, at least one selected from the group consisting of boric acid or its salts, edetic acid or its salts, and chlorhexidine or its salts.
[17] The pollen burst inhibitor according to [16], which contains boric acid or a salt thereof as an active ingredient.
[18] The pollen burst inhibitor according to [16] or [17], wherein the boric acid or a salt thereof is boric acid or borax.
[19] The pollen burst inhibitor according to [17], which further contains edetic acid or a salt thereof.
[20] The pollen burst inhibitor according to [16] or [19], wherein the edetic acid or a salt thereof is sodium edetate hydrate.
[21] The pollen burst inhibitor according to any one of [16] to [20], which further contains polyvinylpyrrolidone.
[22] The pollen burst inhibitor according to any one of [16] to [21], which has a pH of 7.0 or less.
[23] The pollen burst inhibitor according to [22], which has a pH of 6.5 or more and 7.0 or less.
[24] An ophthalmic composition containing the pollen burst inhibitor according to any one of [16] to [23].
[25] The ophthalmic composition of [24], further comprising at least one selected from the group consisting of tonicity agents, stabilizers, thickeners, pH adjusters and solubilizers.
[26] The ophthalmic composition of [24] or [25], which has an osmotic pressure ratio of 1.0 to 1.2.
[27] The ophthalmic composition according to any one of [24] to [26], which is an eyewash or eye drops.
[28] The ophthalmic composition of [27], wherein the eye wash is an eye drop type eye wash.

Furthermore, the present invention also relates to:
[29] Suppression of pollen bursting, comprising contacting pollen with a composition containing, as an active ingredient, at least one selected from the group consisting of boric acid or a salt thereof, edetic acid or a salt thereof, and chlorhexidine or a salt thereof. Method.
[30] The method of [29], wherein the composition contains boric acid or a salt thereof as an active ingredient.
[31] The method of [29] or [30], wherein the boric acid or its salt is boric acid or borax.
[32] The method of [30], wherein the composition further contains edetic acid or a salt thereof.
[33] The method of [29] or [32], wherein the edetic acid or a salt thereof is sodium edetate hydrate.
[34] The method according to any one of [29] to [33], wherein the composition further contains polyvinylpyrrolidone.
[35] The method according to any one of [29] to [34], wherein the pH of the composition is 7.0 or less.
[36] The method of [35], wherein the composition has a pH of 6.5 or more and 7.0 or less.
[37] Any of [29] to [36], wherein the composition further contains at least one selected from the group consisting of tonicity agents, stabilizers, thickeners, pH adjusters and solubilizers. The method described in Crab.
[38] The method of [37], wherein the composition has an osmotic pressure ratio of 1.0 to 1.2.
[39] The method of any one of [29] to [38], wherein the composition is an ophthalmic composition.
[40] An ophthalmic composition comprising only boric acid or its salts, edetic acid or its salts, sodium chloride, potassium chloride, polyvinylpyrrolidone, dilute hydrochloric acid, sodium hydroxide and purified water, and having a pH of 6.5 to 7.0. 0 and an osmotic pressure ratio of 1.0 to 1.2, comprising contacting pollen with an ophthalmic composition.
[41] The method of [39] or [40], wherein the ophthalmic composition is an eye wash or eye drops.
[42] The method of [41], wherein the eye wash is an eye drop type eye wash.

Furthermore, the present invention also relates to:
[43] Use of a composition containing as an active ingredient at least one selected from the group consisting of boric acid or its salts, edetic acid or its salts, and chlorhexidine or its salts for inhibiting pollen bursting.
[44] The use of [43], wherein the composition contains boric acid or a salt thereof as an active ingredient.
[45] The use according to [43] or [44], wherein the boric acid or its salt is boric acid or borax.
[46] The use of [44], wherein the composition further contains edetic acid or a salt thereof.
[47] The use of [43] or [46], wherein the edetic acid or a salt thereof is sodium edetate hydrate.
[48] The use according to any one of [43] to [47], wherein the composition further contains polyvinylpyrrolidone.
[49] The use according to any one of [43] to [48], wherein the pH of the composition is 7.0 or less.
[50] The use of [49], wherein the pH of the composition is 6.5 or more and 7.0 or less.
[51] Any of [43] to [50], wherein the composition further contains at least one selected from the group consisting of tonicity agents, stabilizers, thickeners, pH adjusters and solubilizers use as described in
[52] The use of [51], wherein the composition has an osmotic pressure ratio of 1.0 to 1.2.
[53] The use according to any one of [43] to [52], wherein the composition is an ophthalmic composition.
[54] An ophthalmic composition comprising only boric acid or its salts, edetic acid or its salts, sodium chloride, potassium chloride, polyvinylpyrrolidone, dilute hydrochloric acid, sodium hydroxide and purified water, and having a pH of 6.5-7. 0 and an osmotic pressure ratio of 1.0 to 1.2 for suppressing pollen bursting.
[55] The use of [53] or [54], wherein the ophthalmic composition is an eye wash or eye drops.
[56] The use of [55], wherein the eye wash is an eye drop.

Furthermore, the present invention also relates to:
[57] Pollen rupture, including containing at least one selected from the group consisting of boric acid or a salt thereof, edetic acid or a salt thereof, and chlorhexidine or a salt thereof in a composition that causes pollen rupture. suppression method.

The above [1] to [57] can be arbitrarily selected and combined or applied mutatis mutandis.

INDUSTRIAL APPLICABILITY The present invention can provide a composition for inhibiting pollen bursting that can be incorporated as a pharmaceutically acceptable active ingredient. Since the present composition can suppress pollen bursting, it can be applied to prevent hay fever. For example, by using / incorporating the present composition into compositions such as eye washes and eye drops, pollen burst due to contact between pollen in the eye and the mucous membrane of the eye is suppressed, or pollen in the eye and Since pollen rupture due to contact with a composition such as an eye wash or eye drops is suppressed, pollen can be washed away before allergens are released onto the eye surface, and allergic eye diseases caused by pollen (allergic conjunctivitis, conjunctivitis, etc.) Vernal catarrh, etc.) and aggravation of the disease can be prevented.

It is a figure which shows the pollen burst suppression effect of various components. It is a figure which shows the pollen burst inhibitory effect of various compositions.

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 composition for suppressing pollen bursting of the present invention is intended to suppress the bursting of pollen, and to prevent and/or avoid the release of allergens due to the bursting of pollen. The cause of pollen rupture is not particularly limited, but examples include pollen rupture caused by contact between pollen and pollen rupture factor. Also, the pollen rupture factor is not particularly limited here. Furthermore, pollen rupture may occur due to contact with compositions such as eye drops and eye washes. can suppress/reduce pollen burst caused by contact with Furthermore, the use and / or formulation of this composition is not particularly limited as long as it is intended to suppress pollen bursting, and it can be used as a composition for textile products, a pharmaceutical composition, a food composition (supplements, etc.), etc. and/or formulation is preferred, and use and/or formulation as an ophthalmic composition (eye drops, eye washes, contact lens cleansers) is particularly preferred.

The composition for suppressing pollen bursting of the present invention comprises, as active ingredients, boric acid or its salts, edetic acid or its salts, (benzalkonium or its salts) and chlorhexidine or its salts (group of compounds having an antiseptic effect). ) containing at least one selected from The description of the composition for suppressing pollen bursting of the present invention also applies to the ophthalmic composition, the method for suppressing pollen bursting, and the agent for suppressing pollen bursting of the present invention.

Products containing the composition for suppressing pollen bursting of the present invention include: "boric acid or a salt thereof suppresses pollen bursting", "edetic acid or a salt thereof suppresses pollen bursting", ("benzalkonium or its salts suppress pollen bursting"), "chlorhexidine or its salts suppress pollen bursting", "boric acid or its salts prevent the release of allergens from pollen", and "edetic acid or its salts inhibit pollen bursting"). (“Benzalkonium or its salts prevent the release of allergens from pollen”), “Chlorhexidine or its salts prevent the release of allergens from pollen”, Acid or its salt stops (stops) pollen burst and prevents (blocks) allergic reaction," "Edetic acid or its salt stops (stops) pollen burst ), prevent (block) allergic reactions", ("benzalkonium or its salts stop (stop) pollen burst and prevent (block) allergic reactions"), Labeling such as "chlorhexidine or its salt stops pollen bursting (stops) and prevents (blocks) allergic reactions," or similar labeling may be used. can. 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 the product containing the pollen bursting suppression composition of the present invention, the composition is combined with one active ingredient selected from the group consisting of boric acid or its salts, edetic acid or its salts and chlorhexidine or its salts. Similarly, usefulness can also be indicated, for example, "the present composition suppresses pollen bursting" can be indicated.

In the present invention, boric acid or a salt thereof and its content (concentration) are not particularly limited as long as they are pharmaceutically acceptable. For example, boric acid or a salt thereof includes boric acid and borax, with borax being more preferred. Further, the content thereof is preferably 0.01 to 5% (w/v), more preferably 0.1 to 2% (w/v), and 0.8 to 1.2% (w/v). is particularly preferred.

In the present invention, edetic acid or a salt thereof and its content (concentration) are not particularly limited as long as they are pharmaceutically acceptable. For example, edetic acid or a salt thereof includes edetic acid, sodium edetate, and sodium edetate hydrate, with sodium edetate hydrate being more preferred. In addition, the content is preferably 0.001 to 5% (w/v), more preferably 0.005 to 3% (w/v), particularly 0.01 to 2% (w/v) preferable.

In the present invention, benzalkonium or its salt and its content (concentration) are not particularly limited as long as they are pharmaceutically acceptable. For example, benzalkonium or a salt thereof includes benzalkonium chloride. The content thereof is preferably 0.0001 to 0.02 (w/v), more preferably 0.005 to 0.01 (w/v), and more preferably 0.001 to 0.005 (w/v ) is particularly preferred.

In the present invention, chlorhexidine or a salt thereof and its content (concentration) are not particularly limited as long as they are pharmaceutically acceptable. For example, chlorhexidine or a salt thereof includes chlorhexidine gluconate and chlorhexidine hydrochloride, with chlorhexidine gluconate being more preferred. The content thereof is preferably 0.0001 to 0.02 (w/v), more preferably 0.005 to 0.01 (w/v), and more preferably 0.001 to 0.005 (w/v ) is particularly preferred.

The composition for suppressing pollen bursting of the present invention is characterized by further containing, for example, polyvinylpyrrolidone.

In the present invention, polyvinylpyrrolidone and its content (concentration) are not particularly limited as long as they are pharmaceutically acceptable. Examples of polyvinylpyrrolidone include polyvinylpyrrolidone K15, polyvinylpyrrolidone K30, polyvinylpyrrolidone K60, and polyvinylpyrrolidone K90, with polyvinylpyrrolidone K30 being more preferred. The content thereof is preferably 0.05 to 2.0 (w/v), more preferably 0.1 to 1.5 (w/v), and more preferably 0.3 to 1.0 (w/v ) is particularly preferred.

The pH of the composition for suppressing pollen bursting of the present invention is not particularly limited as long as it is pharmaceutically acceptable. For example, the upper limit is preferably 7.2 or less, more preferably 7.1 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, still more preferably 6.1 or more, and particularly preferably 6.5 or more. In addition, the upper limit and lower limit of the pH can be appropriately combined to form a range, for example, pH is 6.1 or more and 7.2 or less, preferably pH is 6.5 or more and 7.0 or less. . The pH of the composition for suppressing pollen bursting of the present invention can be adjusted using a pH adjuster or buffer (no particular limitation as long as it is pharmaceutically acceptable).

The composition for inhibiting pollen bursting of the present invention may further contain a tonicity agent, a stabilizer, a thickener, a pH adjuster and/or a solubilizer.

The tonicity agent that can be used in the composition for suppressing pollen bursting 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, sodium chloride, carbonate Sodium hydride, sodium carbonate, dry sodium carbonate or magnesium sulfate are preferred, and potassium chloride and sodium chloride are more preferred.

The tonicity agents that can be used in the composition for suppressing pollen bursting of the present invention may be used singly or in 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.

In the composition for suppressing pollen bursting of the present invention, the total content (concentration) of the tonicity agent is, for example, preferably 0.05 to 5% (w / v), 0.1 to 1.8% (w /v) is more preferred, and 0.3 to 0.7% (w/v) is particularly preferred.

The stabilizer that can be used in the composition for suppressing pollen bursting of the present invention is not particularly limited as long as it is pharmaceutically acceptable. For example, trometamol, sodium formaldehyde sulfoxylate (Rongalit), 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 for suppressing pollen bursting of the present invention may be used singly 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.

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

The thickening agent that can be used in the composition for suppressing pollen bursting of the present invention is not particularly limited as long as it is pharmaceutically acceptable. For example, polyvinylpyrrolidones such as polyvinylpyrrolidone K25, polyvinylpyrrolidone K30, polyvinylpyrrolidone K90, 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, etc., 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 for inhibiting pollen bursting of the present invention may substantially or completely contain no sodium hyaluronate (purified sodium hyaluronate, etc.).

The thickening agent that can be used in the composition for inhibiting pollen bursting 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.

In the composition for suppressing pollen bursting of the present invention, the total content (concentration) of the thickening agent is, for example, preferably 0.005 to 1.0% (w / v), 0.01 to 0.5% ( w/v) is more preferred, and 0.3-0.5% (w/v) is particularly preferred.

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

When a pH adjuster is used in the composition for suppressing pollen bursting of the present invention, the total content (concentration) of the pH adjuster is, for example, preferably 0.001 to 5% (w / v), and 0.005 to 1% (w/v) is more preferred, and 0.01-0.5% (w/v) is particularly preferred.

The pH of the composition for suppressing pollen bursting of the present invention is not particularly limited as long as it is pharmaceutically acceptable. For example, the upper limit is preferably 7.2 or less, more preferably 7.1 or less, and particularly preferably 7.0 or less. Moreover, the lower limit thereof is preferably 5.0 or more. 6.0 or more is more preferable, 6.1 or more is still more preferable, and 6.5 or more is particularly preferable. In addition, the upper limit and lower limit of the pH can be appropriately combined to form a range, for example, pH is 6.1 or more and 7.2 or less, preferably pH is 6.5 or more and 7.0 or less. . The pH of the composition for suppressing pollen bursting of the present invention can be adjusted using a pH adjuster or buffer (no particular limitation as long as it is pharmaceutically acceptable).

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 for suppressing pollen bursting 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, sterile purified water, water for injection, distilled water for injection, etc.) are preferred.

The dissolving agent that can be used in the composition for inhibiting pollen bursting 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, formulation form, method of use, and the like of the composition for suppressing pollen bursting.

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

The osmotic pressure of the composition for suppressing pollen bursting 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 for inhibiting pollen bursting of the present invention can contain the following components in appropriate amounts without particular limitation as long as they are pharmaceutically acceptable. 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 tocopheryl 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, potassium dihydrogen phosphate, etc. salts, alkylpolyaminoethylglycine, and the like.

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 purpose of the composition, the formulation form, the method of use, etc. 2017” (2) Ophthalmic Drug Manufacturing and Marketing Approval Standards.

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 for suppressing pollen bursting of the present invention contains the pharmacologically active ingredients of Group A shown in Table 1, it contains up to 3 kinds of pharmacologically active ingredients, and further contains up to 1 kind of pharmacologically active ingredients of Group B, Group C and It preferably contains up to three pharmacologically active ingredients of Group D 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.

The composition for inhibiting pollen bursting of the present invention contains an appropriate amount of the following pharmaceutically acceptable pharmacologically active ingredients (biologically active ingredients or active ingredients) in addition to the above ingredients, as long as the effects of the present invention are not impaired. can also 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 Eye muscle adjusting ingredients (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. In addition, the composition for suppressing pollen bursting of the present invention may not contain sodium hyaluronate at a concentration of 0.075% (w / v) as a pharmacologically active ingredient, and sodium hyaluronate is substantially or completely It does not have to be contained. It may also contain substantially or no polyhexamethylene biguanide.

The pharmacologically active ingredient (physiologically active ingredient or active ingredient) that can be used in the composition for suppressing pollen bursting of the present invention may be used alone or in any combination of two or more. good. 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 for suppressing pollen bursting of the present invention contains an appropriate amount of additives other than the above additives (thickening agent, tonicity agent, stabilizer, pH adjuster, solubilizer) as long as the effects of the present invention are not hindered. can contain. 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 for suppressing pollen bursting 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.

In the composition for suppressing pollen bursting of the present invention, for example, the total content (concentration) of the surfactant is preferably 0.01 to 5% (w / v), and 0.01 to 1% (w / 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 for suppressing pollen bursting 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 for inhibiting pollen bursting 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 compounding components, the application, formulation form, method of use, and the like of the composition for suppressing pollen bursting.

In the composition for suppressing pollen bursting of the present invention, for example, the total content (concentration) of the buffering agent is preferably 0.001 to 5% (w / v), and 0.005 to 3% (w / v) More preferably, 0.01 to 2% (w/v) is particularly preferred.

Preservatives that can be used in the composition for suppressing pollen bursting 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 preferable. The composition for inhibiting pollen bursting of the present invention may substantially or completely contain no polyhexamethylene biguanide.

The preservatives that can be used in the composition for suppressing pollen bursting 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 compounding ingredients, the application, formulation form, method of use, and the like of the composition for suppressing pollen bursting.

In the composition for suppressing pollen bursting of the present invention, for example, the total content (concentration) of preservatives is preferably 0.0001 to 1% (w / v), 0.0005 to 0.5% (w / v ) is more preferable, and 0.001 to 0.2% (w/v) is more preferable, but preservatives, especially benzalkonium or salts thereof, or methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, A composition for inhibiting pollen bursting that does not substantially or completely contain parabens such as butyl paraoxybenzoate or salts thereof is particularly preferred.

The cooling agent that can be used in the composition for suppressing pollen bursting 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 agent that can be used in the composition for suppressing pollen bursting 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 ingredients, the application, formulation form, method of use, and the like of the composition for suppressing pollen bursting.

In the composition for suppressing pollen bursting of the present invention, for example, the total content (concentration) of the cooling agent is preferably 0.001 to 0.5% (w / v), 0.001 to 0.1% ( w/v) is more preferred, and 0.005-0.05% (w/v) is particularly preferred.

The viscosity of the composition for suppressing pollen bursting of the present invention is not particularly limited as long as the viscosity is 12 mPa·s or less and is acceptable as an eye drop. Specifically, the upper limit of the viscosity is preferably 10 mPa·s or less, more preferably 5 mPa·s or less, 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, when the viscosity of the composition for inhibiting pollen bursting of the present invention is 12 mPa·s or less, it has an excellent pollen cleansing effect.

In addition, the viscosity of the composition for inhibiting pollen bursting 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.

When the composition for suppressing pollen bursting of the present invention is used as an eye drop, there is no particular limitation on the dosage (number of times of use, number of eye drops, etc.) as long as it is sufficient to exhibit the desired effect. For example, the frequency of use is preferably 1 to 6 times/day, more preferably 1 to 3 times/day. The number of eye drops is preferably 1 to 3 drops/eye, more preferably 1 to 2 drops/eye, and particularly preferably 1 drop/eye. The frequency of instillation is preferably 1 to 6 times/day, preferably 3 to 6 times/day, and particularly preferably 5 to 6 times/day. The amount of one eye drop is preferably 20 to 60 μL, more preferably 25 to 50 μL, and particularly preferably 30 to 40 μL.

When the composition for suppressing pollen bursting of the present invention is used as an eye wash, the dosage (number of times of use, amount of use, number of eye drops, etc.) is not particularly limited as long as it is sufficient to achieve the desired effect. It can be used in both formula eye wash and eye drop type eye wash. For example, in the case of a cup-type eye wash, the frequency of use is preferably 1 to 6 times/day, more preferably 1 to 3 times/day. Also, the number of times of use is preferably 5 to 10 mL, particularly preferably 5 mL. The frequency of washing the eyes is preferably 1 to 6 times/day, more preferably 3 to 6 times/day. In the case of eye drops, the frequency of use is preferably 1 to 6 times/day, more preferably 3 to 6 times/day. The lower limit of the number of eye drops is preferably 3 drops or more per eye, more preferably 4 drops or more per eye. The upper limit is preferably 8 drops or less per eye, more preferably 6 drops or less per eye. Furthermore, there is no particular limitation on blinking after instillation, but specifically, blinking may be performed after each drop, after instillation of a plurality of drops, or may not be performed. 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. When the number of eye drops is 4 drops or more, an excellent pollen cleansing effect can be obtained.

The composition for suppressing pollen bursting of the present invention can be provided in any container (main body, inner plug, cap). Moreover, the container for containing the composition for suppressing pollen bursting 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 or a single-use unit-dose container.

The composition for suppressing pollen bursting of the present invention can be used as an ophthalmic 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. It can be used even when the contact lens is 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.

When the composition for suppressing pollen bursting of the present invention is used as an eye drop, an appropriate active ingredient can be blended, and it can be used for blurred vision (such as when there is a lot of eye mucus), eye fatigue, conjunctival hyperemia, itchy eyes, Eye disease prevention (after swimming, when dust or sweat gets into the eyes, etc.), blepharitis (soreness of the eyelids), ophthalmia due to ultraviolet rays and other rays (snow blindness, etc.), contact lenses (hard contact lenses, soft contact lenses) etc.) can be used to alleviate, improve, or suppress symptoms such as discomfort during wearing and/or wearing. It can also be used to protect and retain water in the cornea.

When the composition for suppressing pollen bursting of the present invention is used as an eye wash, it can be formulated with an appropriate active ingredient to wash the eyes and prevent eye diseases (after swimming, when dust or sweat gets into the eyes, etc.). can also be used for

The composition for suppressing pollen bursting of the present invention is labeled as "can be used when wearing contact lenses (hard contact lenses / soft contact lenses)", "for use when wearing contact lenses (hard contact lenses / soft contact lenses)", etc. , and can also 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.

Further, the detailed description of the composition for suppressing pollen bursting of the present invention is also applied to the following aspects of the present invention.

One aspect of the present invention comprises contacting pollen with a composition containing at least one selected from the group consisting of boric acid or a salt thereof, edetic acid or a salt thereof and chlorhexidine or a salt thereof as an active ingredient, This is a method for suppressing pollen burst.

One aspect of the present invention is the use of a composition containing, as an active ingredient, at least one selected from the group consisting of boric acid or a salt thereof, edetic acid or a salt thereof, and chlorhexidine or a salt thereof for suppressing pollen bursting. be.

One aspect of the present invention includes containing at least one selected from the group consisting of boric acid or a salt thereof, edetic acid or a salt thereof, and chlorhexidine or a salt thereof in a composition that causes pollen bursting. , is a method for suppressing pollen bursting.

<Formulation example>
Table 2 below shows formulation examples of the composition for suppressing pollen bursting of the present invention, but these formulation examples are 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 is the content in 100 mL of the formulation.

A desired composition for inhibiting pollen bursting can be obtained by appropriately adjusting the types, amounts and viscosities of the pharmacologically active ingredients and additives in Formulation Examples 1 to 6 above.

<Example>
Below, pollen burst suppression effect tests using various components are shown as examples, but this illustration is for better understanding of the present invention and does not limit the scope of the present invention.

[Pollen burst suppression effect test]
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 1.25 times 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 to obtain test solution 1 (comparative example 1).
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 to prepare test liquid 2 (reference example 1).
0.2 g of sodium chloride was added to 40 mL of the 1.25-fold solution 1, and stirred and dissolved. Dilute 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 to prepare test liquid 3 (reference example 2).
0.25 g of polyvinylpyrrolidone K30 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 to prepare test liquid 4 (reference example 3).
0.5 g of boric acid was added to 40 mL of 1.25-fold solution 1, and stirred and dissolved. Dilute 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 to prepare test liquid 5 (Example 1).
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 adjust the total volume to 50 mL to prepare test liquid 6 (Example 2).
0.05 g of 10% benzalkonium chloride solution was added to 40 mL of 1.25 times 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 to prepare test liquid 7 (Example 3).
25 μL of 20% chlorhexidine gluconate 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 to prepare test liquid 8 (Example 4).
Tables 3 and 4 show the compositions of aqueous solutions of test liquids 1-8. Here, disodium hydrogen phosphate hydrate was contained as a pH buffer.

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 1 below.
[Formula 1]
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. Here, FIG. 1 is a graph showing the pollen burst rate of each test solution. Here, the test solution containing boric acid, sodium edetate hydrate, benzalkonium chloride or chlorhexidine gluconate had a pollen burst rate of 15% or less, showing an excellent pollen burst inhibitory effect. On the other hand, potassium chloride, sodium chloride, or polyvinylpyrrolidone K30 showed an effect of promoting pollen bursting.

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 Liquid 160 mL of water was heated to 45° C., 2.0 g of boric acid, 0.8 g of sodium chloride and 0.2 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 make the total volume 50 mL to obtain test solution 9 (Example 5).
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 prepare test liquid 10 (Example 6).
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 make the total volume 50 mL to obtain test liquid 11 (Example 7).
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 to prepare test liquid 12 (Example 8).
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 1.25 times solution 3 was taken, and diluted hydrochloric acid/sodium hydroxide was added to adjust the pH to 7.0 to prepare test solution 13 (Example 9).
320 mL of 1.25 times solution 3 was taken, and diluted hydrochloric acid/sodium hydroxide was added to adjust the pH to 6.5 to prepare test solution 14 (Example 10). Table 5 shows the compositions of the aqueous solutions of test liquids 9 to 14.

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

3) Test results and discussion The test results are shown in FIG. Here, FIG. 2 is a graph showing the pollen burst rate of each test solution. Here, test liquids 9 to 14 had a pollen burst rate of about 20% or less, and these compositions exhibited an excellent pollen burst inhibitory effect. In addition, test liquids 13 and 14 had a pollen burst rate of about 5% or less, and exhibited a particularly excellent pollen burst inhibitory effect. Furthermore, the pollen burst rate was enhanced in a boric acid concentration-dependent manner, and in the presence of boric acid, the concentration-dependent effect of sodium edetate hydrate was enhanced. In the composition of , it was shown that the effect of suppressing pollen bursting is enhanced by lowering the pH. In addition, in the presence of boric acid and sodium edetate hydrate, polyvinylpyrrolidone K30, which is considered to have a pollen bursting promoting effect, complements or enhances the pollen bursting suppressing effect of boric acid and sodium edetate hydrate. It has been suggested.

Claims (7)

Contains 0.8-1.2% (w/v) boric acid or its salt as an active ingredient , and 0.01-0.05% (w/v) edetic acid or its salt, sodium chloride, chloride A composition for suppressing pollen bursting containing potassium, 0.3 to 1.0% (w/v) polyvinylpyrrolidone, a pH adjuster and a solubilizer, and having a pH of 6.5 to 7.0 products (but not containing olopatadine and its salts) . A composition according to claim 1, wherein the boric acid or its salt is boric acid or borax. A composition according to claim 1, wherein the edetic acid or its salt is sodium edetate hydrate. The composition according to any one of claims 1 to 3 , further comprising at least one selected from the group consisting of tonicity agents, stabilizers and thickening agents . The composition according to claim 4 , which has an osmotic pressure ratio of 1.0 to 1.2. A composition according to any one of claims 1 to 5 , wherein the composition is an ophthalmic composition. 0.8-1.2% (w/v) boric acid or its salts, 0.01-0.05% (w/v) edetic acid or its salts, sodium chloride, potassium chloride, 0.3- A composition for suppressing pollen bursting containing 1.0% (w/v) polyvinylpyrrolidone, a pH adjuster and a solubilizer, wherein the composition for suppressing pollen bursting has a pH of 6.5 to 7.0 ( However, it does not contain olopatadine and its salts).

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