Eyewash composition

Abstract

To provide an eyewash composition in which degradation of allantoin is suppressed.SOLUTION: An eyewash composition contains allantoin and hypromellose.SELECTED DRAWING: None

Description

Technical Field

[0001] It relates to an 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 are 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. As an example of the eye-washing method by eye drops, a method of directly dropping an eye-washing solution into the eye to wash the eye can be mentioned (for example, Patent Document 1).

[0003] Allantoin is known as a kind of component having a corneal repair effect and the like. However, since allantoin is easily hydrolyzed, it has poor stability, and particularly, decomposition progresses easily at pH 5 or higher, and it is said that almost all of it decomposes at pH 6. On the other hand, since the above-mentioned eye-washing solution is often at pH 5 or higher, it is important to suppress the decomposition of allantoin in the eye-washing solution.

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-washing composition in which the decomposition of allantoin is suppressed.

Means for Solving the Problems

[0006] In view of the above problems, the present inventor has conducted intensive studies and found that the decomposition of allantoin can be suppressed by blending hypromellose in an eye wash composition containing allantoin. 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 wash composition containing allantoin and hypromellose. Item 2. The eye wash composition according to Item 1, further containing a cooling agent. Item 3. The eye wash composition according to Item 1 or 2, having a pH of 5 to 7.

Effects of the Invention

[0007] By blending hypromellose in an eye wash composition containing allantoin, the decomposition of allantoin can be suppressed. From this, the stability of allantoin in the eye wash composition can be improved.

Modes for Carrying Out the Invention

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

[0009] The eye wash composition included in the present disclosure contains allantoin and hypromellose.

[0010] Allantoin is a known compound represented by the chemical formula C4H6N4O3. In the eye wash composition, the content of allantoin is not limited as long as the effects of the present disclosure can be obtained, but preferably it is 0.003 to 0.05 w / v%, more preferably 0.005 to 0.04 w / v%, still more preferably 0.008 to 0.03 w / v%, and particularly preferably 0.015 to 0.03 w / v%.

[0011] Hypromellose is conventionally known and is also referred to as hydroxypropylmethylcellulose. In the ophthalmic composition, the content of hypromellose is not limited as long as the effects of the present disclosure can be obtained. However, from the viewpoint of further suppressing the decomposition of allantoin in the composition, it is preferably 0.01 to 1 w / v%, more preferably 0.05 to 0.8 w / v%, still more preferably 0.08 to 0.5 w / v%, and particularly preferably 0.15 to 0.5 w / v%. Further, the content of hypromellose is not limited as long as the effects of the present disclosure can be obtained. However, in the ophthalmic composition, per 1 part by mass of allantoin, it is preferably 0.01 to 20 parts by mass, more preferably 0.1 to 20 parts by mass, still more preferably 1 to 20 parts by mass, and particularly preferably 3.5 to 20 parts by mass.

[0012] The ophthalmic composition may further contain a cooling agent. Examples of the cooling agent include menthol, camphor, borneol, etc. When there are d-form, l-form, and dl-form in the cooling agent, it does not matter which one, and any of them may be used. The cooling agent may be used alone or in combination of two or more. When the cooling agent is contained, its content is not limited. However, from the point of further suppressing the decomposition of allantoin in the composition, in the composition, it is preferably 0.0001 to 0.05 w / v%, more preferably 0.0005 to 0.01 w / v%, still more preferably 0.001 to 0.008 w / v%. Further, the content of the cooling agent is not limited as long as the effects of the present disclosure can be obtained. However, in the ophthalmic composition, per 1 part by mass of allantoin, it is preferably 0.005 to 5 parts by mass, more preferably 0.01 to 1 part by mass, still more preferably 0.05 to 1 part by mass.

[0013] The ophthalmic composition of the present disclosure may further contain any other components acceptable for use in eye drops or eye washes. Examples of the other components include, but are not limited to, buffers, stabilizers, isotonic agents, solvents, pH adjusters, medicinal components, preservatives, etc. The other components may be appropriately selected according to the purpose, etc., as long as they do not interfere with the effects of the present disclosure, and may be used alone or in combination of two or more, and the blending amount may also be determined appropriately.

[0014] As an example of the other components, if a buffering agent is mentioned, boric acid, borax, etc. are exemplified as the buffering agent. 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, and more preferably 0.5 to 2 w / v% is exemplified. For example, when the composition contains borax, the content of borax is not limited as long as it does not interfere with the effects of the present disclosure. In the composition, preferably 0.005 to 0.5 w / v% is exemplified, and more preferably 0.005 to 0.05 w / v% is exemplified. The composition may or may not contain a buffering agent other than boric acid and borax.

[0015] As an example of the other components, if a stabilizer is mentioned, polysorbate (polysorbate 80, polysorbate 60, etc.), polyoxyethylene (POE) hydrogenated castor oil (POE(80) hydrogenated castor oil, POE(60) hydrogenated castor oil, etc., the numbers in parentheses mean the average number of moles of ethylene oxide added), sodium edetate (including hydrate), etc. are exemplified. These may be used alone or in combination of two or more. When the composition contains a stabilizer, its content is not limited as long as it does not interfere with the effects of the present disclosure. In the composition, preferably 0.01 to 0.5 w / v% is exemplified, and more preferably 0.05 to 0.5 w / v% is exemplified. When the composition contains a stabilizer, for example, polysorbate, it may contain only any one or only two selected from polysorbate, polyoxyethylene hydrogenated castor oil and sodium edetate. Also, for example, when it contains polysorbate, it can be prepared without blending polyoxyethylene hydrogenated castor oil and / or sodium edetate.

[0016] As an example of the other components, if a medicinal ingredient is mentioned, amino acids, anti-inflammatory agents, corneal surface protectants, antihistamines, vitamins, etc. are exemplified as the medicinal ingredient. These may be used alone or in combination of two or more.

[0017] Although not limiting the present disclosure, examples of amino acids include amino acids and their salts such as glutamic acid and its salts (sodium glutamate, etc.); amino acid analogs such as taurine. These may be used alone or in combination of two or more. The eye wash composition of the present disclosure can also be prepared without blending an amino acid and / or its salt. The amino acid referred to herein 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. Further, the eye wash composition of the present disclosure can also be prepared without blending an amino acid analog.

[0018] Although not limiting the present disclosure, examples of 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 limiting the present disclosure, the composition preferably does not contain zinc sulfate and / or zinc lactate. Further, the composition can also be prepared without blending epsilon-aminocaproic acid, glycyrrhizic acid and its salts.

[0019] Although not limiting the present disclosure, examples of corneal surface protectants include chondroitin sulfate and its salts, hyaluronic acid and its salts, etc., and preferred salts include alkali metal salts such as sodium salt. These may be used alone or in combination of two or more. Although not limiting the present disclosure, examples of the molecular weight of chondroitin sulfate and its salts preferably have a weight average molecular weight of about 0.5 to 45,000, more preferably about 15,000 to 30,000. Further, although not limiting the present disclosure, the composition can also be prepared without blending chondroitin sulfate and its salts and / or hyaluronic acid and its salts.

[0020] Without limiting the present disclosure, examples of antihistamines include diphenhydramine and its salts (such as diphenhydramine hydrochloride), chlorpheniramine and its salts (such as chlorpheniramine maleate), and the like. These may be used alone or in combination of two or more. Without limiting the present disclosure, the composition can also be prepared without incorporating diphenhydramine and its salts and / or chlorpheniramine and its salts.

[0021] When the composition of the present disclosure contains a medicinal ingredient, the content of the medicinal ingredient is not limited as long as the effects of the present disclosure are not hindered. In the composition, the content of the medicinal ingredient is preferably 0.01 - 5 w / v%, more preferably 0.025 - 4 w / v%, and even more preferably 0.1 - 3 w / v%. Although allantoin mentioned above is also known as a medicinal ingredient, this ingredient is not included in the description of the medicinal ingredient in the present disclosure. Therefore, the content of allantoin is not included in the content of the medicinal ingredient.

[0022] As an example of the other components, preservatives include quaternary ammonium salt - based preservatives, para - hydroxybenzoic acid esters, chlorobutanol, sorbic acids, and the like. Examples of quaternary ammonium - based preservatives include benzalkonium chloride, benzetonium chloride, and the like. Examples of para - hydroxybenzoic acid esters include para - hydroxybenzoic acid esters such as methyl para - hydroxybenzoate, propyl para - hydroxybenzoate, butyl para - hydroxybenzoate, and salts of para - hydroxybenzoic acid esters (such as alkali metal salts like sodium salt). Examples of sorbic acids include sorbic acid, salts of sorbic acid (such as alkali metal salts like sodium salt, potassium salt), and the like. These may be used alone or in combination of two or more. Without limiting the present disclosure, the composition preferably does not contain a preservative. Without limiting the present disclosure, as can be understood from the examples described later, the eye - washing composition of the present disclosure can also be prepared without incorporating a preservative.

[0023] The eye-washing composition of the present disclosure can be produced by mixing allantoin, hypromellose, a cooling agent if necessary, and other components.

[0024] The pH of the eye-washing composition of the present disclosure is not limited as long as it is within the range that can be used as an eye drop or an eye-washing agent. However, at room temperature (25°C), the pH is preferably 5 to 8, more preferably 5.5 to 7, still more preferably 5.5 to 6.5, further more preferably 5.5 to 6, and particularly preferably 5.5 to 5.8 from the viewpoint of improving the preservability of the composition. The pH is measured with a desktop pH meter F-52 (manufactured by Horiba, Ltd.).

[0025] The form of the eye-washing composition of the present disclosure is liquid at room temperature, and its usage method is not limited as long as it can wash the eyes in the same manner as a conventionally known method. Usually, it is used for eye washing with an eye cup or for eye washing by eye drops. Therefore, the composition is contained in a container and is used by pouring it from the container into an eye cup or by directly dropping it from the container into the eyes. The viscosity and osmotic pressure (osmotic pressure ratio) of the composition are not limited as long as it can be used in this way.

[0026] The eye-washing 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.

[0027] The eye-washing composition of the present disclosure is not limited as long as it can be used as described above. However, when it is used with an eye cup, it is usually contained in a conventionally known general container (for example, including a container body and a cap) as described in the following examples. The container may be of a type in which the container body and the cap are independent or an integrated type, and may have an inner stopper (inner lid). The inner stopper may have a hole for pouring the eye-washing composition into the eye cup. The capacity of the container is not limited either, but from the viewpoint of good usability, etc., the capacity is preferably 400 to 550 mL, more preferably 450 to 550 mL.

[0028] Eye washing using an eye wash cup may be performed according to normal procedures. For example, an appropriate amount of the eye wash composition of the present disclosure, such as 4 to 6 mL per eye per application, is poured from the container into the eye wash cup, and then the cup is pressed against the periphery of one eye to bring the eye wash composition in the cup into contact with the eye, and it is used by blinking several times. The number of times of use per day of the composition is not limited either, and may be, for example, any of 1 to 6 times, 2 to 6 times, 3 to 6 times, etc. per eye per day. In this way, the eyes can be washed.

[0029] In addition, when the eye wash composition of the present disclosure is used for eye washing by eye drops, from the viewpoint of good usability and the like, the composition is usually contained in an eye drop container for use. 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 (for example, including a container body, an inner stopper (nozzle), and a cap) used in conventionally known eye drops, eye drop type eye washes, etc. are exemplified. The eye drop container may be of 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, etc.

[0030] The capacity of the eye drop container is not limited, but from the viewpoint of good usability and the like, examples of the capacity are 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] Eye washing by instillation is performed by instilling 3 to 8 drops of the eye wash composition of the present disclosure per eye per time. Without being limited thereto, 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 per time. The drop volume per drop is not limited either, but examples thereof include 35 to 40 μL, more preferably 35 to 37 μL per drop. Also, the number of times of use of the composition 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. In this way, the eyes can be washed.

[0032] Thus, by blending hypromellose into the eye wash composition containing allantoin, the decomposition of allantoin can be suppressed. From this, the stability of allantoin in the eye wash composition can be improved. Also, when the composition further contains the above-mentioned medicinal components, etc., useful effects based on the medicinal components, etc. can also be provided.

Examples

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

[0034] Test Example 1. Preparation and Stability Evaluation of Eye-Washing Composition Each component was mixed according to the blending ratios shown in Table 1 below to prepare each composition (Examples 1 to 6, Comparative Examples 1 and 2). The pH of each composition immediately after production was measured. The pH was measured at room temperature (25 °C) using a desktop pH meter F-52 (manufactured by Horiba, Ltd.). 500 mL of the obtained composition was filled into an eye wash cup (eye cup) (Eye Bon AL d, manufactured by Kobayashi Pharmaceutical Co., Ltd.) in an eye wash agent container (capacity 500 mL, Eye Bon AL d, manufactured by Kobayashi Pharmaceutical Co., Ltd.) After capping, it was left standing and stored at 50°C in the dark for one month. Separately, 10 mL of each of the obtained compositions was placed in an eye wash container for eye drops (capacity 13 mL, made of polyethylene terephthalate resin, multi-dose type, manufactured by Shin-Koh Chemical Co., Ltd.), capped, and then left standing and stored at 50°C in the dark for one month. For each composition immediately after preparation and each composition after storage at 50°C in the dark for one month, the content of allantoin was quantified by HPLC (High Performance Liquid Chromatography).

[0035] Taking the content of allantoin in each composition immediately after preparation as 100%, the ratio of allantoin in each composition after storage in the eye wash container was calculated, and the value obtained by rounding off the second decimal place was taken as the residual rate (%) of allantoin.

[0036] 2. Results The results are shown in Table 1. Table 1 shows the results when stored in an eye wash container with an eye wash cup.

[0037]

Table 1

[0038] In the composition of Comparative Example 1 containing allantoin and not containing hypromellose, the residual rate of allantoin was 86.4%, and the residual rate of allantoin was not sufficient. In contrast, in Examples 1 and 2 in which hypromellose was used in combination with allantoin, the residual rates of allantoin improved to 90.1% and 91.1% respectively, and the stability of allantoin improved. On the other hand, in Comparative Example 2 in which hydroxyethyl cellulose was used in combination with allantoin, the residual rate of allantoin was 85.2%, and the stability of allantoin rather decreased compared with Comparative Example 1.

[0039] From this, it was confirmed that the use of hypromellose can suppress the reduction of allantoin in the eye wash composition and improve the stability. Also, although hypromellose and hydroxyethyl cellulose are common in that they belong to cellulose-based thickeners, when hypromellose and allantoin are used in combination, the stability of allantoin can be improved, whereas it was found that the stability of allantoin cannot be improved even when hydroxyethyl cellulose and allantoin are used in combination.

[0040] In addition, in Examples 3 to 5 in which menthol or borneol, or both menthol and borneol were used in combination with allantoin and hypromellose, the residual rate of allantoin was further improved, and the stability of allantoin could be further improved. From this, it was confirmed that the stability of allantoin in the eye wash composition can be further improved by further using a cooling agent such as menthol and borneol in combination with allantoin and hypromellose. Example 6 is a modification of Example 5 with the pH changed to 5.5, and further improvement in the stability of allantoin was observed in Example 6. Although not shown in the table, when the content of menthol in Example 3 was increased to 0.006 w / v%, the stability of allantoin was further improved. Also, when the content of borneol in Example 4 was increased to 0.006 w / v%, the stability of allantoin was further improved. It was also confirmed that the stability of allantoin can be improved in the same manner in each composition contained in the eye drop type eye wash container.

[0041] Formulation Example Table 2 shows formulation examples of the eye wash composition contained in the eye wash container with an eye cup of the present disclosure. When the residual rate of allantoin was evaluated in the same manner as in the test examples for the formulation examples shown in Table 2, it was confirmed that the stability of allantoin was improved in any of Formulation Examples 1 to 5 as compared with the case where hypromellose was not contained in Formulation Examples 1 to 5. Also, in the same manner in each composition contained in the eye drop type eye wash container, it was confirmed that the stability of allantoin was improved. In the same manner in each composition contained in the eye drop type eye wash container, it was confirmed that the stability of allantoin was improved.

[0042]

Table 2

Claims

[Claim 1] An eyewash composition containing allantoin and hypromellose.

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