Eye drop type eye wash composition

Abstract

To provide eye drop type eye wash compositions having the reduced and alleviated irritation of refreshing agents and having a pleasant refreshing feeling, and also to provide methods for reducing the irritation of refreshing agents.SOLUTION: Provided is an eye drop type eye wash composition containing at least one selected from the group consisting of tocopherol acetate and polysorbate 80, and a refreshing agent. Also provided is a method for reducing irritation caused by a refreshing agent of the eye drop type eye wash composition, comprising adding at least one selected from the group consisting of tocopherol acetate and polysorbate 80 to the eye drop type eye wash composition containing a refreshing agent.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a drop-type eyewash composition. [Background technology]

[0002] Conventionally, eye washing methods using an eye cup (eye cup) have been known, and one example of such a method is to pour an appropriate amount of eye wash (for example, about 5 mL) into the eye cup, then press the cup against the area around one eye to bring the eye wash in the cup into contact with the eye, and then blink several times to wash the eye. However, this method requires an eye cup, and has a problem of lack of portability.

[0003] Another method of washing the eyes that is different from the above method is known, which is to drop an eyewash solution directly onto the eyes (for example, Patent Document 1). This method has the advantage of being highly portable since it does not require an eyewash cup. Eyewashing by eyedrops is usually performed by dropping the eyedrop solution into the eyeball more frequently than eye drops, for example, about 3 to 12 drops per eye. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] JP 2019-210265 A Summary of the Invention [Problem to be solved by the invention]

[0005] The inventors have found that eye washing using eye drops causes stronger irritation to the eyeball than eye washing using eye drops or the above-mentioned eye washing cup, and that in particular, when washing the eyes with a drop-type eyewash solution containing a refreshing agent, the irritation is greater than the pleasant feeling of freshness. Therefore, the present invention aims to provide a method for reducing the irritation caused by the refreshing agent in a drop-type eyewash composition containing a refreshing agent. [Means for solving the problem]

[0006] The present inventors have conducted intensive research in view of the above problems, and have found that by adding at least one selected from the group consisting of tocopherol acetate and polysorbate 80 to a drop-type eyewash composition containing a refreshing agent, eye irritation during eyewashing using the drop-type eyewash composition containing a refreshing agent can be reduced. The present invention has been completed as a result of further research based on this finding. The present invention includes the following embodiments.

[0007] Item 1. An eye drop-type eyewash composition comprising at least one selected from the group consisting of tocopherol acetate and polysorbate 80, and a cooling agent. Item 2. The eye drop-type eyewash composition according to Item 1, wherein the freshening agent is at least one selected from the group consisting of menthol, camphor, borneol and geraniol. Item 3. The eye drop-type eyewash composition according to Item 1 or 2, which does not contain at least one selected from the group consisting of antihistamines, thickeners, amino acid salts, and quaternary ammonium compound-based preservatives. Item 4. The drop-type eyewash composition according to any one of Items 1 to 3, which is used by instilling 3 to 8 drops per eye at a time. Item 5. Regarding a drop-type eyewash composition containing a cooling agent, a manufacturing method for reducing the irritation caused by the cooling agent, comprising, in addition to the cooling agent, tocopherol acetate and polysorbate 80 The method according to any one of claims 1 to 5, further comprising the step of blending at least one selected from the group consisting of: Item 6. A method for reducing irritation caused by a cooling agent in an eye drop type eyewash composition, comprising blending at least one selected from the group consisting of tocopherol acetate and polysorbate 80 in the eye drop type eyewash composition containing a cooling agent. Effect of the Invention

[0008] According to the present invention, it is possible to provide a drop-type eyewash composition that reduces the irritation caused by the refreshing agent when washing the eyes by eye drop application. The drop-type eyewash composition of the present invention has reduced irritation caused by the refreshing agent and has a pleasant refreshing feeling. Furthermore, according to the method of the present invention, it is possible to reduce the irritation caused by the refreshing agent in an eyedrop-type eyewash composition that contains a refreshing agent. Therefore, according to the method of the present invention, it is possible to obtain an eyedrop-type eyewash composition that has reduced irritation caused by the refreshing agent and has a pleasant refreshing feeling. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0009] The present invention provides an eye drop-type eyewash composition containing at least one member selected from the group consisting of tocopherol acetate and polysorbate 80, and a cooling agent.

[0010] The refreshing agent may be any agent that can be applied to the eyes as a component of the eyewash composition, and examples thereof include menthol, camphor, borneol, isoborneol, geraniol, anethole, eugenol, limonene, cymene, terpineol, pinene, cineole, citronellol, carvone, menthone, linalool, linalool acetate, linalyl acetate, and essential oils containing these (e.g., eucalyptus oil, bergamot oil, peppermint oil, cool mint oil, spearmint oil, peppermint oil, fennel oil, cinnamon oil, rose oil, camphor oil, etc.). When the refreshing agent has d-, l-, and dl-isomers, any of them may be used. Menthol, camphor, borneol, and geraniol, which have strong irritation, are preferred, and menthol, which has sharp irritation, is more preferred. These refreshing agents may be used alone or in combination of two or more. When two or more kinds are used, there is no upper limit, but examples include 2 to 5 kinds, 2 to 4 kinds, and 2 to 3 kinds.

[0011] The content of the cooling agent in the drop-type eyewash composition of the present invention is not limited, but can be selected from the range of 0.0005 to 0.5 w / v%, preferably 0.001 to 0.05 w / v%, more preferably 0.001 to 0.02 w / v%, further preferably 0.003 to 0.012 w / v%, and particularly preferably 0.003 to 0.009 w / v%.

[0012] The tocopherol acetates used in the present invention include α, γ or δ-tocopherol. and acetate esters. Preferred is an ester of α-tocopherol and acetate. The tocopherol acetate may be any one that can be applied to the eye as a component of an eyewash composition, and examples of such tocopherol acetate include dl-α-tocopherol acetate and d-α-tocopherol acetate. Preferred is d-α-vitamin E, also known as natural vitamin E. It is methyl ether acetate.

[0013] The blending ratio of tocopherol acetate in the drop-type eyewash composition of the present invention can be appropriately selected from the range of 0 to 0.005 w / v%. When tocopherol acetate is blended, it can be selected from the range of preferably 0.0005 to 0.005 w / v%, more preferably 0.001 to 0.005 w / v%. By blending tocopherol acetate in this range, the irritation of the separately blended cooling agent can be reduced and a comfortable cooling sensation can be imparted to the drop-type eyewash composition blended with a cooling agent. Although not limited, the blending ratio of tocopherol acetate to 100 parts by mass of the cooling agent in the drop-type eyewash composition is preferably in the range of 20 to 125 parts by mass. More preferably, The amount is preferably 50 to 125 parts by mass, and more preferably 60 to 125 parts by mass.

[0014] Polysorbate 80 is a polyoxyethylene ether in which part of the hydroxyl groups of sorbitol anhydride has been esterified with oleic acid, and is a nonionic surfactant also known as polyoxyethylene (20) sorbitan oleate, polyoxyethylene sorbitan oleate, or Tween 80.

[0015] The blending ratio of polysorbate 80 in the drop-type eyewash composition of the present invention can be appropriately selected from the range of 0 to 0.5 w / v%. When polysorbate 80 is blended, it can be preferably selected from the range of 0.01 to 0.3 w / v%, more preferably 0.05 to 0.15 w / v%. By blending polysorbate 80 in this range, the irritation of the separately blended cooling agent can be reduced and a comfortable refreshing feeling can be imparted to the cooling agent-blended drop-type eyewash composition. In addition, although not limited, the blending ratio of polysorbate 80 to 100 parts by mass of the cooling agent in the drop-type eyewash composition is preferably in the range of 120 to 7500 parts by mass. More preferably, it is 800 to 3800 parts by mass, and even more preferably, it is 1200 to 2500 parts by mass.

[0016] The tocopherol acetate and polysorbate 80 can be combined in the eye drop type eyewash composition of the present invention. By using both in combination, the effect of reducing and mitigating the irritation of the cooling agent can be further enhanced, and the effect of imparting a pleasant cooling sensation to the eye drop type eyewash composition containing a cooling agent can be enhanced. When using both in combination, the blending ratio of the tocopherol acetate and polysorbate 80 can be, for example, in the range of 1 to 10 parts by mass of the tocopherol acetate per 100 parts by mass of the polysorbate 80 in the eye drop type eyewash composition containing a cooling agent. It is preferably 2 to 7 parts by mass, more preferably 2.5 to 5 parts by mass.

[0017] The eye drop type eyewash composition of the present invention may contain any other component that is acceptable for use in eye drop or eyewash. Examples of such other components include, but are not limited to, medicinal components, buffers, stabilizers, isotonicity agents, solvents, pH adjusters, thickeners, preservatives, etc. The other components may be appropriately selected according to the purpose, etc., as long as they do not impair the effects of the present invention, and may be used alone or in combination of two or more types, and the amount of each component may be appropriately determined.

[0018] Here, examples of the medicinal ingredient include, but are not limited to, vitamins, amino acids, corneal surface layer protective agents, anti-inflammatory agents (antiphlogistic agents), antihistamines, etc. These may be used alone or in combination of two or more. A combination of two or more is preferred, and examples include 2 to 5 types, 2 to 4 types, or 2 to 3 types.

[0019] Although the present invention is not limited thereto, examples of amino acids include amino acids or pharma- ceutical acceptable salts thereof; amino acid analogs such as taurine, etc. These may be used alone or in combination of two or more. Preferred are amino acid analogs such as taurine, which are known to be useful as nutrients for ocular tissues to activate the tissues and promote recovery from eye fatigue and eye diseases. The eye drop-type eyewash composition of the present invention can be prepared without blending amino acids and / or pharma-ceutical acceptable salts thereof. The amino acid referred to here means an α-amino acid that can be a structural unit of a protein having both amino and carboxy functional groups, and includes, for example, L-aspartic acid.

[0020] Although not limiting the present invention, examples of the corneal surface layer protective agent include chondroitin sulfate, hyaluronic acid, or a pharma- ceutically acceptable salt thereof, preferably chondroitin sulfate or a pharma- ceutically acceptable salt thereof. The salt of chondroitin sulfate is not particularly limited as long as it is pharma- ceutically acceptable, but preferably includes alkali metal salts (sodium salt, potassium salt, etc.); alkaline earth metal salts (calcium salt, magnesium salt, etc.). When chondroitin sulfate or its salt is blended as a corneal surface protective agent in the drop-type eyewash composition of the present invention, it is preferable not to blend hyaluronic acid or its salt.

[0021] Although not limiting the present invention, examples of anti-inflammatory agents (anti-inflammatory agents) include zinc sulfate, zinc lactate, epsilon-aminocaproic acid, glycyrrhizic acid and its salts (dipotassium glycyrrhizinate, etc.). These may be used alone or in combination of two or more. Although not limited, the eye drop type eyewash composition of the present invention preferably does not contain zinc sulfate and / or zinc lactate.

[0022] Although not limiting the present invention, examples of antihistamines include diphenhydramine and its salts (diphenhydramine hydrochloride, etc.), chlorpheniramine and its salts (chlorpheniramine maleate, etc.). These may be used alone or in combination of two or more. Although not limiting the present invention, the eye drop type eyewash composition of the present invention is preferably one that does not contain an antihistamine, and in particular, it is preferable that it does not contain chlorpheniramine and its salts.

[0023] When the eye drop type eyewash composition of the present invention contains these medicinal ingredients, the blending ratio of each medicinal ingredient may be any amount that can be used for eyewash, as long as it does not impair the effects of the present invention.

[0024] In addition, a conventional buffering agent can be used without limitation, but preferably, boric acid and its salts (e.g., sodium salt) can be mentioned. A preferred salt of boric acid is borax (sodium tetraborate). The content of boric acid is not limited as long as it does not impede the effects of the present invention, but is exemplified as 0.2 to 2.5 w / v%, preferably 0.5 to 2.2 w / v%, and more preferably 1 to 2 w / v% in the drop-type eyewash composition of the present invention. The content of borax is not limited as long as it does not impede the effects of the present invention, but is exemplified as 0.001 to 0.6 w / v%, preferably 0.002 to 0.1 w / v%, and more preferably 0.003 to 0.05 w / v% in the drop-type eyewash composition of the present invention.

[0025] In addition, any conventional stabilizer can be used without limitation, and preferably, sodium edetate hydrate is exemplified. As long as the effect of the present invention is not hindered, the content of the stabilizer is not limited, and is exemplified as 0.001 to 0.5 w / v%, and preferably, 0.005 to 0.4 w / v%.

[0026] The eye drop type eyewash composition of the present invention may contain any conventional thickener without any restrictions, but preferably does not contain any thickener.

[0027] In addition, although any conventional preservative can be used without restriction, the eye drop eyewash composition of the present invention preferably does not contain any preservative, particularly no quaternary ammonium preservatives (e.g., benzalkonium chloride, benzethonium chloride, etc.).

[0028] As one embodiment of the present invention, without being limiting the present invention, the eye drop-type eyewash composition of the present invention contains (1) at least one selected from the group consisting of tocopherol acetate and polysorbate 80, (2) a cooling agent, and (3) at least one selected from the group consisting of medicinal ingredients, buffers, corneal surface protective agents, stabilizers, isotonicity agents, solvents, and pH adjusters, and does not contain thickeners and / or preservatives (particularly quaternary ammonium-based preservatives).

[0029] In addition, as one embodiment of the present invention, the present invention is not limited to the above-mentioned eye drop formulation. The eyewash composition contains (1) at least one selected from the group consisting of tocopherol acetate and polysorbate 80, (2) a cooling agent, and (3) at least one selected from the group consisting of medicinal ingredients, buffers, corneal surface protective agents, stabilizers, isotonicity agents, solvents, and pH adjusters.

[0030] Furthermore, as one embodiment of the present invention, although not intended to be limiting, the eye drop-type eyewash composition of the present invention is exemplified by one that does not contain amino acids and their salts (particularly aspartic acid and its salts) as the medicinal ingredients, and one that does not contain antihistamines (particularly chlorpheniramine maleate).

[0031] The eye drop-type eyewash composition of the present invention can be produced by mixing at least one selected from the group consisting of tocopherol acetate and polysorbate 80, a cooling agent, and, if necessary, the other ingredients described above.

[0032] The pH of the eye drop type eyewash composition of the present invention is not limited as long as it is within a range that can be used as an eyewash, and is exemplified by pH 5 to 8, preferably pH 5.5 to 7.5, and more preferably pH 6 to 7.5 at room temperature (24° C.). The pH is measured with a tabletop pH meter F-52 (manufactured by Horiba, Ltd.).

[0033] The form of the drop-type eyewash composition of the present invention is not limited, and is usually liquid at room temperature.

[0034] The eye drop type eyewash composition of the present invention is usually contained in an eye drop container and instilled in the eye. For this reason, the viscosity of the composition is not limited as long as it can be instilled in the eye, but is preferably 0.9 to 2.5 mPa·s, more preferably 0.9 to 1.6 mPa·s, and even more preferably 0.9 to 1.2 mPa·s at room temperature. The viscosity was measured using a cone-plate viscometer (rheometer MCR302, manufactured by Anton Paar) at a shear rate of 100 s -1The measurement is performed at a measurement temperature of 25°C. More specifically, 5 mL of the composition is added to the sample plate of the rheometer, a cone plate sensor with a radius of 50 mm and a cone angle of 1° is set, and the shear rate is 100 s at 25°C. -1 The sensor is rotated so that the viscosity is measured. Measurements are carried out for 100 seconds, with one point of data being obtained every 2 seconds, and the average value of the five data points, 45th to 49th, is calculated and used as the viscosity.

[0035] The osmolality of the eye drop type eyewash composition of the present invention is not limited as long as it is within the range usable as an eye drop or eyewash, but for example, the osmolality ratio is 0.6 to 1.6, preferably 0.7 to 1.3, and more preferably 0.8 to 1.2. The osmolality ratio is a value measured and calculated using an automatic osmolality analyzer (OsmoStation OM-6060, manufactured by Arkray, Inc.) according to 2.47 Osmolality Measurement Method (Osmolarity Measurement Method) of the 17th Revised Japanese Pharmacopoeia, and is a value obtained by measuring the osmolality of the composition and physiological saline (0.9 w / v% sodium chloride aqueous solution) and assuming the measured value of physiological saline to be 1.

[0036] The eye drop-type eyewash composition of the present invention may be used with or without contact lenses, regardless of whether the contact lenses are hard or soft.

[0037] The eye drop type eyewash composition of the present invention is not limited as long as it can be used by instillation, but from the viewpoint of ease of use, the composition is usually contained in an eye drop container before use.

[0038] The eye drop container is not limited as long as it can contain the composition and can be used to instill the composition in the eye. Examples of the eye drop container include eye drop containers (including, for example, a container body, an inner stopper (nozzle), and a cap) that are used for conventionally known eye drops and eye drop-type eyewashes. The eye drop container includes a container body, an inner stopper (nozzle), and a cap. The type may be any of the following: a type in which each of the nozzles is independent; a type in which at least two of the container body, inner stopper (nozzle), and cap are integrated; a type in which the inner stopper (nozzle) has a hole; a type in which the inner stopper (nozzle) has no hole and a hole is made in the inner stopper (nozzle) by tightening the cap when using.

[0039] The volume of the eye drop container is not limited, but from the viewpoint of ease of use, the volume is, for example, 8 to 20 mL, preferably 10 to 15 mL, and more preferably 12 to 14 mL. The volume may be appropriately determined taking into consideration whether the eye drop container is a multi-dose type or a unit-dose type.

[0040] The eye drop type eyewash composition of the present invention is used by instilling 3 to 8 drops per eye at one time. Although not limited thereto, the composition is preferably instilled 4 to 8 drops per eye at one time, more preferably 4 to 6 drops, from the viewpoint of reducing and mitigating the irritation of the separately blended cooling agent and imparting a pleasant cooling sensation to the cooling agent-containing eye drop type eyewash composition.

[0041] The amount of the composition to be dropped per drop is not limited as long as the effects of the present invention can be obtained, but is exemplified by 30 to 50 μL, preferably 35 to 40 μL, and more preferably 35 to 37 μL per drop.

[0042] The number of times the composition is used per day is not particularly limited, and may be, for example, 1 to 12 times, 2 to 8 times, 3 to 6 times, etc. per eye per day.

[0043] In this way, the eye drop type eyewash composition of the present invention can cleanse the eyes. In particular, since the composition contains at least one selected from the group consisting of tocopherol acetate and polysorbate 80 in addition to the refreshing agent, it can reduce and alleviate the irritation of the refreshing agent, thereby providing a comfortable refreshing feeling when instilled into the eyes. In addition, when the composition further contains the above-mentioned medicinal ingredient, it can provide a useful medicinal effect based on the medicinal ingredient.

[0044] From this, it can be said that the present invention also provides a method for reducing the irritation caused by a cooling agent in an eye drop type eyewash composition containing a cooling agent, by incorporating at least one member selected from the group consisting of tocopherol acetate and polysorbate 80 into the eye drop type eyewash composition containing a cooling agent.

[0045] In this method, the description of the eye drop-type eyewash composition, tocopherol acetate, polysorbate 80, and cooling agent and the amounts of each of them to be used are as described above, and the above descriptions are similarly applied to the method of the present invention. EXAMPLES

[0046] The present invention will be described in more detail below with reference to Test Examples and Examples, but the present invention is not limited to these.

[0047] Test Example 1 The subjects were asked to wash their eyes by dropping the eye wash composition prepared by the following method, and to evaluate the comfort and tingling sensation due to the refreshing sensation.

[0048] 1. Preparation of eye drop type eyewash composition A drop-type eyewash composition was prepared by mixing each component according to the mixing ratio shown in Tables 1 and 2. 13 mL of the prepared composition was filled into a general eyedrop container (capacity 15 mL, made of polyethylene terephthalate resin, multi-dose type, manufactured by Shinko Chemical Co., Ltd.) and used as an eyedrop-type eyewash in an eyedrop container. Ophthalmic compositions were obtained (Examples 1 to 12 and Comparative Examples 1 and 2).

[0049] 2. Test Method Four subjects were first asked to wash both eyes with physiological saline using an eyecup, and the test was started after 5 minutes had passed. In the test, each drop-type eyewash composition was dropped from an eyedropper to one eye, 5 drops at a time, so as to wash the eye, and after the drop, the subjects were asked to evaluate the comfort and irritation caused by the refreshing feeling. Each drop-type eyewash composition was evaluated once for each subject, and was evaluated comprehensively from the scores of the four subjects. In addition, 30 minutes after the evaluation of one drop-type eyewash composition was completed, both eyes were washed with physiological saline using an eyecup, and 5 minutes after the eyewash with physiological saline, the next drop-type eyewash composition was evaluated in the same manner as above.

[0050] [Irritation evaluation] The irritation was evaluated using the VAS method (0: no irritation felt, 100: strong irritation felt). Specifically, four subjects were asked to rate the sensation of irritation in the eyes after washing compared to that after not washing, based on the VAS method. The subjects were asked to give a score (VAS value) in comparison with the untreated eye, and the VAS improvement rate (%) was calculated from the average value according to the following formula, and the value rounded off to one decimal place was regarded as the improvement rate (%) of irritation sensation. Examples 1 to 6 were based on Comparative Example 1, and Examples 7 to 12 were based on Comparative Example 2. In the VAS method, the state of "100: strong irritation" is determined by adding 0.05 w / v % benzalkonium chloride to the drop-type eyewash composition of Comparative Example 2. The irritation sensation of the eyes after washing with the standard preparation prepared as above was evaluated by a VAS score of 90. After fine-tuning the issues and reaching a common understanding, the tests were carried out.

[0051]

number

[0052] [Evaluation of comfort based on cool sensation] Four subjects were asked to choose from four options (comfortable, somewhat comfortable, somewhat uncomfortable, uncomfortable) to rate the comfort of the cool feeling of washed eyes compared to unwashed eyes. The results were evaluated according to the following criteria. ◎: All four people answered "comfortable" ○: 3 people answered "comfortable" △: 2 people answered "comfortable" ×: 0 to 1 person answered "comfortable"

[0053] 3. Test Results The results are shown in Tables 1 and 2. [Table 1] [Table 2]

[0054] From the results of Examples 1 and 2 in Table 1, it was confirmed that by adding tocopherol acetate in addition to l-menthol to the drop-type eyewash composition, the irritation of l-menthol was reduced and alleviated depending on the amount of the tocopherol acetate, and a comfortable refreshing feeling was obtained. Also, from the results of Examples 3 to 5, it was confirmed that by adding polysorbate 80 in addition to l-menthol to the drop-type eyewash composition, the irritation of l-menthol was reduced and alleviated depending on the amount of the tocopherol acetate, and a comfortable refreshing feeling was obtained. Also, as can be seen from the results of Example 6, a more excellent effect was obtained by using both in combination. Furthermore, as shown in Table 2, it was confirmed that these effects were similarly obtained even if the amount of l-menthol was doubled from 0.004 w / v% to 0.008 w / v%.

[0055] From these findings, it was found that by incorporating at least one of tocopherol acetate and polysorbate 80 into an eye drop-type eyewash composition containing a cooling agent, the sharp irritation caused by the cooling agent can be mitigated, and a pleasant cooling sensation can be imparted.

[0056] Prescription Examples Table 3 shows examples of formulations of the eye drop type eyewash composition of the present invention. According to the compositions shown in Formulation Examples 1 to 9, by containing tocopherol acetate and polysorbate 80 together with one or more kinds of cooling agents, it was confirmed that the irritation to the eyes during washing was reduced and alleviated, and a comfortable cooling sensation was obtained, compared to a drop type eyewash composition not containing tocopherol acetate and polysorbate 80. [Table 3]

Claims

[Claim 1] An eye drop type eyewash composition comprising at least one member selected from the group consisting of tocopherol acetate and polysorbate 80, and a cooling agent.

Images