Eye drop-type eyewash composition

Abstract

To provide an eye drop-type eyewash composition and the like having excellent antiseptic properties.SOLUTION: The eye drop-type eyewash composition contains 0.005-0.03 w / v% of allantoin and does not contain any antiseptic agents selected from quaternary ammonium salt-based antiseptic agents, p-hydroxybenzoic acid esters, chlorobutanol, and sorbic acid.SELECTED DRAWING: None

Description

Technical Field

[0001] It relates to an eye-drop type eye-washing composition.

Background Art

[0002] Conventionally, an eye-washing method using an eye-washing cup (eye cup) and an eye-washing method by eye drops have been known. As an example of the eye-washing method using an eye-washing cup, an appropriate amount (for example, about 5 mL) of an eye-washing solution is poured into the eye-washing cup, and then the cup is pressed against the periphery of one eye to bring the eye-washing solution in the cup into contact with the eye, and the eye is washed by blinking several times. Also, as an example of the eye-washing method by eye drops, a method of directly dropping an eye-washing solution into the eye for eye-washing is known (for example, Patent Document 1).

[0003] Compared with the eye-washing method using an eye-washing cup, the eye-washing method by eye drops has advantages such as excellent portability because an eye-washing cup is not required and is easy to use even when away from home. Thus, the eye-washing method by eye drops is convenient to use, but since it is directly dropped into the eye and is often used when away from home, the risk of the eye-washing solution being exposed to microbial contamination is also high. In order to reduce such a contamination risk, it is known to incorporate a preservative such as benzalkonium chloride into the eye-washing solution. However, from the viewpoints of the influence on the cornea and adsorption to contact lenses, etc., the incorporation of such a preservative tends not to be preferable. For this reason, there is a demand for an eye-drop type eye-washing composition having excellent antiseptic properties without incorporating a preservative such as benzalkonium chloride.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0005] Therefore, an object of the present disclosure is to provide an eye-drop type eye wash composition having excellent antiseptic properties.

Means for Solving the Problems

[0006] The present inventor conducted intensive studies in view of the above problems, and found that when a specific amount of allantoin is blended in an eye-drop type eye wash composition, the desired antiseptic property can be imparted to the eye-drop type eye wash composition without blending a preservative. The present invention has been completed by further studies based on such findings. That is, the present disclosure includes the following inventions. Item 1. An eye-drop type eye wash composition containing allantoin at 0.005 to 0.03 w / v% and not containing a preservative selected from quaternary ammonium salt-based preservatives, paraoxybenzoic acid esters, chlorobutanol, and sorbic acids. Item 2. The eye-drop type eye wash composition according to Item 1, further containing at least one selected from the group consisting of chlorpheniramine and its salts. Item 3. The eye-drop type eye wash composition according to Item 1 or 2, further containing tocopherol acetate.

Effects of the Invention

[0007] By blending allantoin in an eye-drop type eye wash composition not containing a preservative selected from quaternary ammonium salt-based preservatives, paraoxybenzoic acid esters, chlorobutanol, and sorbic acids so as to be 0.005 to 0.03 w / v%, an antiseptic action can be imparted to the eye wash composition. Thus, it is possible to provide an eye-drop type eye wash composition containing allantoin at 0.005 to 0.03 w / v% and not containing the preservative and having the antiseptic action imparted thereto. Item 22. It is possible to provide an eye-drop type eye wash composition containing allantoin at 0.005 to 0.03 w / v% and not containing the preservative.

Modes for Carrying Out the Invention

[0008] Hereinafter, embodiments included in the present disclosure will be described in more detail.

[0009] The eye-drop type eye wash composition included in the present disclosure contains allantoin at 0.005 to 0.03 w / v% and does not contain a preservative selected from quaternary ammonium salt-based preservatives, paraoxybenzoic acid esters, chlorobutanol, and sorbic acids.

[0010] Allantoin is a known compound represented by the chemical formula C4H6N4O3. In the eye-drop type eye wash composition, the content of allantoin is 0.005 to 0.03 w / v%. Although not limited thereto, from the viewpoint of improving the preservative property of the composition, the content of allantoin in the composition is preferably 0.006 to 0.03 w / v%, more preferably 0.01 to 0.03 w / v%, and still more preferably 0.015 to 0.03 w / v% as an example.

[0011] The composition does not contain a preservative selected from quaternary ammonium salt-based preservatives, paraoxybenzoic acid esters, chlorobutanol, and sorbic acids. The preservative is a conventionally known preservative in the fields of eye drops and eye washes. Examples of the quaternary ammonium-based preservative include benzalkonium chloride and benzethonium chloride. Examples of paraoxybenzoic acid esters include paraoxybenzoic acid esters such as methyl paraoxybenzoate, propyl paraoxybenzoate, and butyl paraoxybenzoate, and salts of paraoxybenzoic acid esters (alkali metal salts such as sodium salt). Examples of sorbic acids include sorbic acid and salts of sorbic acid (alkali metal salts such as sodium salt and potassium salt, alkaline earth metals such as calcium salt and magnesium salt).

[0012] The composition may further contain at least one selected from the group consisting of chlorpheniramine and its salts. Chlorpheniramine and its salts are known as antihistamines, and the salts of chlorpheniramine are not limited, but examples of the salts include chlorpheniramine maleate. These may be used alone or in combination of two or more. When chlorpheniramine and its salts are contained, the content thereof is not limited, but from the viewpoint of improving the preservativeness of the composition, the total amount of at least one selected from the group consisting of chlorpheniramine and its salts in the composition is preferably 0.0002 to 0.005 w / v%, more preferably 0.0003 to 0.004 w / v%, still more preferably 0.0005 to 0.003 w / v%, and particularly preferably 0.001 to 0.003 w / v% are exemplified. Also, the content of one selected from the group consisting of chlorpheniramine and its salts is not limited as long as the effects of the present disclosure can be obtained, but in the composition, per 1 part by mass of the content of allantoin, preferably 0.03 to 1.5 parts by mass, more preferably 0.08 to 1.5 parts by mass, still more preferably 0.1 to 1 part by mass are exemplified.

[0013] The composition may further contain tocopherol acetate. Tocopherol acetate includes esters of α, γ or δ-tocopherol and acetic acid. Tocopherol acetate is preferably exemplified by esters of α-tocopherol and acetic acid, etc., such as dl-α-tocopherol acetate, d-α-tocopherol acetate (natural vitamin E), etc., and preferably dl-α-tocopherol acetate, etc. are exemplified. These may be used alone or in combination of two or more. When tocopherol acetate is contained, the content thereof is not limited, but from the viewpoint of improving the preservativeness of the composition, in the composition, preferably 0.001 to 0.007 w / v%, more preferably 0.0015 to 0.006 w / v%, still more preferably 0.002 to 0.005 w / v% are exemplified. Also, the content of tocopherol acetate is within the scope of the present disclosure Although not limited as long as the indicated effects can be obtained, in the composition, per 1 part by mass of allantoin content, preferably 0.01 to 1.5 parts by mass, more preferably 0.05 to 1 part by mass, still more preferably 0.08 to 1 part by mass are exemplified.

[0014] The ophthalmic eye-washing composition of the present disclosure may further contain any other components acceptable for use in eye drops and eye washes. Examples of the other components, which do not limit the present disclosure, include buffering agents, stabilizers, isotonic agents, solvents, pH adjusters, thickening agents, medicinal ingredients, cooling agents, and the like. The other components may be appropriately selected according to the purpose and the like, as long as they do not interfere with the effects of the present disclosure. They may be used alone or in combination of two or more, and their blending amounts may also be determined appropriately.

[0015] As an example of the other components, when a buffering agent is mentioned, examples of the buffering agent include boric acid, borax, and the like. The buffering agent may be used alone or in combination of two or more. For example, when the composition contains boric acid, the content of boric acid is not limited as long as it does not interfere with the effects of the present disclosure. In the composition, preferably 0.1 to 2.5 w / v% is exemplified, more preferably 0.2 to 1.5 w / v% is exemplified. When the composition contains borax, the content may also be determined appropriately. Further, the composition may contain both, for example, boric acid and borax, or may contain only one of them. Also, the composition may or may not contain a buffering agent other than boric acid and borax.

[0016] As an example of the other components, stabilizers include, for example, polysorbates (polysorbate 80, polysorbate 60, polysorbate 20, etc.), sodium edetate (including hydrates), and the like. These may be used alone or in combination of two or more. When the composition contains a stabilizer, the content of the stabilizer is not limited as long as the effects of the present disclosure are not impaired. In the composition, preferably 0.001 to 0.5 w / v% is exemplified, and more preferably 0.01 to 0.2 w / v% is exemplified. When the composition contains a stabilizer, for example, it may contain only one kind selected from polysorbate and sodium edetate, or only two kinds, or may be an eye wash composition without containing these.

[0017] As an example of the other components, medicinal components include, as medicinal components, amino acids, anti-inflammatory agents (anti-inflammatory drugs), corneal surface protectants, antihistamines, and the like. These may be used alone or in combination of two or more.

[0018] Although not limiting the present disclosure, for example, as amino acids, amino acids and their salts such as glutamic acid and its salts (sodium glutamate, etc.); amino acid analogs such as taurine, etc. are exemplified. These may be used alone or in combination of two or more. Note that the composition of the present disclosure can be prepared without blending amino acids and / or their salts. Here, the amino acid means an amino acid that can be a constituent unit of a protein having both functional groups of an amino group and a carboxyl group, and includes, for example, L-aspartic acid and the like. Also, the eye wash composition of the present disclosure can be prepared without blending amino acid analogs.

[0019] Although not limiting the present disclosure, for example, as anti-inflammatory agents, zinc sulfate, zinc lactate, epsilon-aminocaproic acid, glycyrrhizic acid and its salts (dipotassium glycyrrhizinate, etc.) and the like are exemplified. These may be used alone or in combination of two or more. Note that although not limiting the present disclosure, the composition of the present disclosure preferably does not contain zinc sulfate and / or zinc lactate.

[0020] Although not limiting the present disclosure, for example, as a corneal surface protective agent, chondroitin sulfate and its salts, hyaluronic acid and its salts, etc. are exemplified, and as the salt, preferably sodium salt, etc. Alkali metal salts such as those are exemplified. These may be used alone or in combination of two or more. When the composition of the present disclosure contains chondroitin sulfate and / or its salt, the composition can also be prepared without containing hyaluronic acid and its salt. Although not limiting the present disclosure, as the molecular weight of chondroitin sulfate or its salt, preferably the weight average molecular weight is about 0.5×10⁴ to 4.5×10⁴, more preferably about 1.5×10⁴ to 3×10⁴. The weight average molecular weight used in the examples described later is measured by gel filtration chromatography.

[0021] When the composition of the present disclosure contains a medicinal ingredient, as long as the effects of the present disclosure are not hindered, the content of the medicinal ingredient is not limited, and in the composition, the content of the medicinal ingredient is preferably 0.01 to 1 w / v%, more preferably 0.025 to 0.5 w / v%, and even more preferably 0.1 to 0.3 w / v%. Although the aforementioned allantoin, chlorpheniramine and its salts are also known as medicinal ingredients, these ingredients are not included in the description of the medicinal ingredient in the present disclosure. Therefore, the content of allantoin, chlorpheniramine and its salts is not included in the content of the medicinal ingredient.

[0022] When the eye-drop type eye-washing composition of the present disclosure contains a cooling agent, menthol, camphor, borneol, etc. are exemplified. When there are d-form, l-form, dl-form in the cooling agent, their differences are not questioned. The cooling agent may be used alone or in combination of two or more. The content of the cooling agent is not limited as long as the effects of the present disclosure are not hindered, and in the composition, preferably 0.0001 to 0.05 w / v%, more preferably 0.002 to 0.01 w / v%.

[0023] The eye-drop type eye-wash composition of the present disclosure can be produced by mixing allantoin, at least one selected from the group consisting of chlorpheniramine and its salts as required, tocopherol acetate, and other components. Here, allantoin is mixed so as to be 0.005 to 0.03 w / v% in the composition. Further, the composition does not contain a preservative selected from quaternary ammonium salt-based preservatives, paraoxybenzoic acid esters, chlorobutanol, and sorbic acids.

[0024] Therefore, as an embodiment of the eye-drop type eye-wash composition of the present disclosure, (1) containing 0.005 to 0.03 w / v% of allantoin, and optionally (2) at least one selected from the group consisting of chlorpheniramine and its salts, optionally (3) tocopherol acetate, optionally (4) a buffer, a stabilizer, an isotonic agent, a solvent, a pH adjuster, a thickener, a medicinal ingredient, and a cooling agent. A composition containing at least one selected from the group and not containing a preservative selected from quaternary ammonium salt-based preservatives, paraoxybenzoic acid esters, chlorobutanol, and sorbic acids is exemplified. Further, as the embodiment, a composition comprising the component (1) and at least one selected from the group consisting of the components (2) to (4) is exemplified. Further, as shown in the examples described later, as the embodiment, a composition not containing components generally used as preservatives in the fields of eye drops and eye washes is exemplified.

[0025] The pH of the eye-drop type eye-wash composition of the present disclosure is not limited as long as it is within a range usable as an eye drop or an eye wash. However, at room temperature (24°C), the pH is 5 to 8. From the viewpoint of improving the preservativeness of the composition, preferably the pH is 5.5 to 7, more preferably the pH is 5.5 to 6.5, still more preferably the pH is 5.5 to 6, particularly preferably the pH is 5.5 to 5.8, and particularly more preferably the pH is 5.5 to 5.7. The pH is measured with a desktop pH meter F-52 (manufactured by Horiba, Ltd.). The form of the composition of the present disclosure is not limited, and it is usually liquid at room temperature.

[0026] The eye-drop type eye-wash composition of the present disclosure is usually contained in an eye-drop container and instilled as described below. Therefore, the viscosity and osmotic pressure (osmotic pressure ratio) of the composition are not limited as long as it can be used in this way.

[0027] The eye-drop type eye-wash composition of the present disclosure may be used with contact lenses worn or without contact lenses worn. The contact lenses may be either hard contact lenses or soft contact lenses.

[0028] The eye-drop type eye-wash composition of the present disclosure is not limited as long as it can be used by instillation, but from the viewpoint of good usability, etc., the composition is usually contained in an eye-drop container and used.

[0029] The eye-drop container is not limited as long as it can contain the composition and be used for eye drops. For example, eye-drop containers (including, for example, a container body, an inner stopper (nozzle), and a cap) used in conventionally known eye drops and eye-drop type eye-washes are exemplified. The eye-drop container may be of any type, such as a type in which the container body, the inner stopper (nozzle), and the cap are each independent, a type in which at least two of the container body, the inner stopper (nozzle), and the cap are integrated, a type in which a hole is provided in the inner stopper (nozzle), or a type in which there is no hole in the inner stopper (nozzle) and a hole is opened in the inner stopper (nozzle) by tightening the cap during use.

[0030] The capacity of the eye-drop container is not limited, but from the viewpoint of good usability, etc., examples of the capacity include 8 to 20 mL, preferably 10 to 15 mL, and more preferably 12 to 14 mL. The capacity may be appropriately determined in consideration of the difference between the multi-dose type and the unit-dose type.

[0031] The eye-drop type eye-washing composition of the present disclosure is used by instilling 3 to 8 drops per eye once. Without being limited to this extent, from the viewpoint of more efficiently washing the eyes, the composition is preferably instilled with 4 to 8 drops, more preferably 4 to 6 drops, per eye once. The drop volume per drop is not limited either, but examples include 30 to 50 μL per drop, preferably 35 to 40 μL, and more preferably 35 to 37 μL. Also, the number of times of use per day of the composition is not particularly limited, and for example, it may be any of 1 to 12 times, 2 to 8 times, 3 to 6 times, etc. per eye per day. In this way, the eye can be washed according to the eye-drop type eye-washing composition of the present disclosure.

[0032] Thus, in the eye-drop type eye-washing composition of the present disclosure, although no preservative selected from quaternary ammonium salt-based preservatives, paraoxybenzoic acid esters, chlorobutanol, and sorbic acids is formulated, by formulating allantoin so as to be 0.005 to 0.03 w / v%, an antiseptic action can be imparted to the eye-drop type eye-washing composition. Further, when the composition further contains the above-mentioned medicinal ingredients, etc., useful effects based on the medicinal ingredients, etc. can also be provided.

Examples

[0033] Hereinafter, the present disclosure will be described in more detail with examples, but the present disclosure is not limited thereto.

[0034] Test Example 1 1. Preparation of an ophthalmic eye wash composition and evaluation of its preservative effect Each component was mixed according to the mixing ratios shown in Table 1 below to prepare each composition (Examples 1 to 8, Comparative Examples 1 to 2, and Reference Example). 10 mL of the obtained composition was poured into a general eye-drop type eye-washing agent container (capacity 13 mL, made of polyethylene terephthalate resin, multi-dose type, manufactured by Shinko Chemical Co., Ltd.). Next, a liquid (bacterial solution) in which Candida albicans was suspended in sterilized physiological saline was added to each container at 1×10 7Inoculated to reach cfu / mL and stored at 30°C in the dark for 21 days. After storage, 0.1 mL of each composition inoculated with Candida was taken out from the container, and this was applied with a spreader stick to a commercially available GPLP agar medium (GPLP agar medium "Daiichi", manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.), cultured at 30°C for 48 hours, the number of colonies was visually counted, and the value obtained by multiplying the counted value by 100 was taken as the number of bacteria in each composition 21 days after storage. Taking the number of bacteria at the time of inoculation as 100%, the ratio (survival rate) of the number of bacteria in each composition after 21 days of storage was calculated. The antiseptic power of the eye-drop type eye-wash composition was evaluated according to the following criteria from the calculated values. [Evaluation Criteria] ◎: The survival rate decreased to 0.05% or less of the inoculum ○: The survival rate decreased to 0.1% or less of the inoculum △: The survival rate decreased to 3% or less of the inoculum ×: Does not meet the criteria of the above △

[0035] Also, the pH of each composition immediately after preparation was measured. The pH was measured at room temperature (24°C) using a desktop pH meter F-52 (manufactured by Horiba, Ltd.).

[0036] 2. Results The results are shown in Table 1.

[0037]

Table 1

[0038] The reference example with the addition of benzalkonium chloride, a representative preservative, means the positive control in this test example. As shown in Table 1, the evaluation result was ◎, and it had excellent antiseptic power. In the reference example, the Candida survival rate in the composition after storage was 0.001%. On the other hand, in Comparative Example 1 prepared in the same manner as the reference example except for not adding benzalkonium chloride, and in Comparative Example 2 prepared without adding benzalkonium chloride and instead adding chlorpheniramine maleate, the evaluation results were ×, and the desired antiseptic power could not be obtained.

[0039] In contrast, in Example 1 in which allantoin was contained at 0.006 w / v% instead of benzalkonium chloride, the evaluation result was ○, and the desired antiseptic power was obtained. In Example 1, the survival rate was 0.100%, that is, the survival rate decreased to 0.1% or less of the inoculum. Also, in Example 2 in which the content of allantoin was increased in Example 1, the evaluation result was ◎, and a higher antiseptic power was obtained. Also, in Examples 3 to 6 in which chlorpheniramine maleate was used in combination with allantoin, the evaluation results were also ◎, and a high antiseptic power was obtained. In Examples 4 to 6 in which the pH of the composition of Example 3 was lowered, the antiseptic property was further improved. The survival rates in Examples 2 to 6 were 0.050%, 0.010%, 0.008%, 0.005%, and 0.004%, respectively. Furthermore, the evaluation results of Examples 7 to 8 in which allantoin, chlorpheniramine maleate, and dl-α-tocopherol acetate were used in combination were ◎, and the survival rates in Examples 7 to 8 were 0.001% and 0%, respectively, and the antiseptic property was significantly improved. From this, it was confirmed that by adding allantoin to an eye wash composition not containing a preservative, also by adding allantoin and chlorpheniramine maleate, and further by adding allantoin, chlorpheniramine maleate, and dl-α-tocopherol acetate, a desired antiseptic action can be imparted or enhanced to the eye wash composition.

[0040] Test Example 2 1. Preparation of an ophthalmic eye wash composition and evaluation of its preservative effect Each component was mixed according to the mixing ratios shown in Table 2 below, and each composition was prepared (Examples 9 and 10, Comparative Example 3). In the table, sodium chondroitin sulfate was topical-grade sodium chondroitin sulfate (manufactured by Seikagaku Corporation, weight-average molecular weight 20,000). The pH of each composition immediately after preparation was measured in the same manner as in Test Example 1.

[0041] After passing 10 mL of each of the obtained compositions through a sterilizing filter, they were placed into general eye-drop type eye-wash containers (the same as in Test Example 1) that had been sterilized. Ten panelists were asked to instill 4 drops into each eye once a day, three times a day for 5 days, from the eye-drop containers containing each composition, and a general bacterial count test was conducted on each composition remaining in the containers.

[0042] The general bacterial count test was performed according to the following procedure. 1 mL of the composition remaining in the container was collected. All 1 mL of each composition collected from 10 samples was mixed to obtain a 10 mL mixed solution. 1 mL was collected from the obtained mixed solution, diluted 10-fold with sterilized water, and the total amount was applied to a standard agar medium (Standard Agar Medium (Granules) "Nissui", manufactured by Nissui Pharmaceutical Co., Ltd.) and cultured at 35°C for 48 hours. After culturing, the number of colonies was visually counted, and the value obtained by multiplying the counted number by 10 was taken as the general bacterial count (cfu / mL) (detection limit value: 10 cfu / mL).

[0043] 2. Results The results are shown in Table 2.

[0044]

Table 2

[0045] As shown in Table 2, the general bacterial count of Comparative Example 3 which did not contain allantoin was 100 cfu / mL. In contrast, in Examples 9 and 10 to which allantoin, chlorpheniramine maleate, and dl-α-tocopherol acetate were added, the general bacterial count could be suppressed to non-detectable (below the detection limit). In the case of an eye-drop type cleanser, it is considered that bacteria are likely to contaminate the composition in the container due to the high frequency of contact with the eyelashes. Thus, in the eye-drop type eye wash which is easily contaminated with bacteria, the increase in the bacterial count could be suppressed in Examples 9 and 10. Further, when evaluated in the same manner for the compositions obtained by modifying the compositions of Examples 9 and 10 so as not to contain only allantoin, the general bacterial count could not be suppressed to non-detectable. From this also, it was confirmed that by blending allantoin, chlorpheniramine maleate, and dl-α-tocopherol acetate into the eye-drop type eye wash composition not containing a preservative, a desired preservative effect can be imparted or enhanced to the eye-drop type eye wash composition.

[0046] Formulation Example Formulation examples of the eye-drop type eye wash composition of the present invention are shown in Table 3. When the preservative power was evaluated for the formulation examples shown in Table 3 in the same manner as in Test Examples 1 and 2, it was confirmed that all of the compositions of Formulation Examples 1 to 8 were excellent in preservative properties as compared with the case where they did not contain allantoin.

[0047]

Table 3

Claims

【Claim 1】 An eye drop type eye wash composition containing allantoin at 0.005 to 0.03 w / v% and not containing a preservative selected from quaternary ammonium salt-based preservatives, paraoxybenzoic acid esters, chlorobutanol, and sorbic acids.

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