JP7693286B2 - Eye drop type eyewash composition - Google Patents

Description

The present invention relates to a drop-type eyewash composition.

Conventionally, eyewashing methods using an eyewash cup (eyecup) have been known. One example of this method is to pour an appropriate amount of eyewash liquid (e.g., about 5 mL) into the eyewash cup, then press the cup against the area around one eye to bring the liquid in the cup into contact with the eye, and then blink several times to wash the eye. However, this method requires an eyewash cup, which has the problem of being poorly portable.

A different method of washing the eyes is known, which involves dropping eyewash directly onto the eyes (see, for example, Patent Document 1). This method is highly portable because it does not require an eyewash cup. However, this method requires less eyewash to be applied to the eyes than the above method, and there is a risk that the eyewash effect will be insufficient.

JP 2019-210265 A

Therefore, the present invention aims to provide a drop-type eyewash composition that can effectively remove foreign matter, and to provide a method for improving the effect of removing foreign matter.

The present inventors have conducted intensive research in view of the above problems and have found that the effect of removing foreign matter in a drop-type eyewash composition can be improved by blending at least one selected from the group consisting of chondroitin sulfate and its salts in the drop-type eyewash composition. The present invention has been completed as a result of further research based on the above findings, and is as follows.
Item 1. A drop-type eyewash composition containing at least one selected from the group consisting of chondroitin sulfate and its salts.
Item 2. The drop-type eyewash composition according to Item 1, further comprising at least one selected from the group consisting of boric acid and borax.
Item 3. The drop-type eyewash composition according to Item 1 or 2, which does not contain at least one selected from the group consisting of a thickener, a preservative, and an antihistamine.
Item 4. The drop-type eyewash composition according to any one of Items 1 to 3, which is administered in an amount of 3 to 8 drops per eye at a time.
Item 5. A method for improving the foreign matter removing effect of a drop-type eyewash composition, comprising blending at least one selected from the group consisting of chondroitin sulfate and salts thereof into the drop-type eyewash composition.

According to the present invention, it is possible to provide a drop-type eyewash composition that can effectively remove foreign matter, and also to improve the foreign matter removal effect of the drop-type eyewash composition.

The present invention will be described in more detail below.

The present invention provides a drop-type eyewash composition containing at least one selected from the group consisting of chondroitin sulfate and its salts.

The eye drop-type eyewash composition of the present invention contains at least one selected from the group consisting of chondroitin sulfate and its salts. Chondroitin sulfate is a mucopolysaccharide having a structure in which sulfate is ester-bonded to a sugar chain in which the disaccharides of D-glucuronic acid and N-acetylgalactosamine are repeated, and is a known substance.

Examples of salts of chondroitin sulfate include, but are not limited to, alkali metal salts such as sodium salts and potassium salts, and alkaline earth metal salts such as magnesium salts and calcium salts. Examples of salts of chondroitin sulfate include, but are not limited to, sodium chondroitin sulfate ester.

The chondroitin sulfate and its salts used in the present invention are not limited to these, but from the viewpoint of further improving the foreign matter removal effect, the molecular weight is preferably about 5,000 to 45,000, more preferably about 10,000 to 40,000, and even more preferably about 15,000 to 30,000. The weight average molecular weight is measured by gel filtration chromatography. Chondroitin sulfate and its salts are commercially available, for example, under the product name Extraordinary Sodium Chondroitin Sulfate (manufactured by Seikagaku Corporation, weight average molecular weight 20,000).

The content of at least one selected from the group consisting of chondroitin sulfate and its salts is not limited as long as the effects of the present invention are obtained. From the viewpoint of further improving the effect of removing foreign matter, the content in the drop-type eyewash composition of the present invention is, for example, 0.005 to 0.5 w/v%, preferably 0.005 to 0.4 w/v%, more preferably 0.006 to 0.3 w/v%, even more preferably 0.007 to 0.1 w/v%, and particularly preferably 0.008 to 0.08 w/v%.

The drop-type eyewash composition of the present invention may contain boric acid. There are no limitations on the content of boric acid as long as it does not interfere with the effects of the present invention. From the viewpoint of further improving the effect of removing foreign matter, the content of boric acid in the drop-type eyewash composition of the present invention is, for example, 0.2 to 2.5 w/v%, preferably 0.5 to 2.2 w/v%, more preferably 1 to 2 w/v%, even more preferably 1.2 to 2 w/v%, and particularly preferably 1.4 to 1.8 w/v%.

The drop-type eyewash composition of the present invention may contain borax. There are no limitations on the amount of borax contained as long as it does not impede the effects of the present invention. From the viewpoint of further improving the effect of removing foreign matter, the amount of borax contained in the drop-type eyewash composition of the present invention is, for example, 0.001 to 0.6 w/v%, preferably 0.002 to 0.1 w/v%, more preferably 0.003 to 0.05 w/v%, even more preferably 0.005 to 0.025 w/v%, and particularly preferably 0.01 to 0.02 w/v%.

The eye drop-type eyewash composition of the present invention may further contain any other component that is acceptable for use in eye drops or eyewashes. Examples of such other components include, but are not limited to, medicinal ingredients, stabilizers, isotonicity agents, cooling agents, solvents, pH adjusters, thickeners, preservatives, etc. The other components may be appropriately selected depending on the purpose, etc., and may be used alone or in combination of two or more types, and the amounts of the other components may be appropriately determined.

Although the present invention is not limited to this, examples of other components that may be mentioned include medicinal ingredients such as amino acids, vitamins, anti-inflammatory agents (anti-phlogistic agents), corneal surface protective agents, and antihistamines. These may be used alone or in combination of two or more.

When the eye drop type eyewash composition of the present invention contains a medicinal ingredient, the present invention is not limited thereto, but preferably contains at least one selected from the group consisting of amino acids, vitamins, anti-inflammatory agents (antiphlogistic agents), corneal surface protective agents, and antihistamines, more preferably contains 1 to 5 types selected from the group, and even more preferably contains 2 to 4 or 2 to 3 types selected from the group.

Although not limiting the present invention, examples of amino acids include amino acids and their salts such as glutamic acid and its salts (e.g., monosodium glutamate); amino acid analogs such as taurine, and the like, and preferably amino acid analogs such as taurine. These may be used alone or in combination of two or more. The eye drop eyewash composition of the present invention can be prepared without blending an amino acid and/or a salt thereof. The amino acid referred to here means an amino acid that can be a constituent unit of a protein having both amino and carboxy functional groups, and includes, for example, L-aspartic acid.

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

Although this invention is not limited thereto, examples of corneal surface protective agents include hyaluronic acid and its salts (e.g., sodium hyaluronate), but the eye drop eyewash composition of the present invention can be prepared without blending hyaluronic acid and/or its salts.

When the eye drop-type eyewash composition of the present invention contains a medicinal ingredient, the content of the medicinal ingredient is not limited as long as it does not impede the effects of the present invention. The content of the medicinal ingredient in the composition is, for example, 0.01 to 1 w/v%, preferably 0.025 to 0.8 w/v%, more preferably 0.05 to 0.5 w/v%, even more preferably 0.1 to 0.4 w/v%, and particularly preferably 0.13 to 0.3 w/v%. Although chondroitin sulfate and its salts are also known as medicinal ingredients, these ingredients are not included in the description of the medicinal ingredients herein, and therefore the content of the medicinal ingredient does not include the content of chondroitin sulfate and its salts.

When the eye drop-type eyewash composition of the present invention contains a stabilizer, the stabilizer may be used alone or in combination of two or more kinds. The content of the stabilizer is not limited as long as it does not interfere with the effects of the present invention, and examples of the stabilizer content in the composition include 0.001 to 0.5 w/v%, preferably 0.05 to 0.2 w/v%, and more preferably 0.08 to 0.12 w/v%.

When the drop-type eyewash composition of the present invention contains an isotonicity agent, the isotonicity agent may be used alone or in combination of two or more. The content of the isotonicity agent is not limited as long as it does not impede the effects of the present invention, and can be appropriately selected from the range of 0.3 to 2 w/v% in the composition so that the osmotic pressure ratio of the composition (relative to physiological saline) is in the range of 0.6 to 1.6 as described below.

When the eye drop-type eyewash composition of the present invention contains a refreshing agent, the refreshing agent may be used alone or in combination of two or more kinds. The content of the refreshing agent is not limited as long as it does not interfere with the effects of the present invention, and examples of the content of the refreshing agent in the composition include 0.0001 to 0.6 w/v%, preferably 0.002 to 0.01 w/v%, and more preferably 0.004 to 0.008 w/v%.

As one embodiment of the present invention, the eye drop eyewash composition of the present invention includes at least one selected from the group consisting of chondroitin sulfate and its salts, without limiting the present invention.

In one embodiment of the present invention, the eye drop eyewash composition of the present invention contains at least one selected from the group consisting of chondroitin sulfate and its salts, as well as boric acid and/or borax, without limiting the present invention.

In addition, as one embodiment of the present invention, the eye drop-type eyewash composition of the present invention includes (1) at least one selected from the group consisting of chondroitin sulfate and its salts, (2) boric acid and/or borax, and (3) at least one selected from the group consisting of medicinal ingredients, stabilizers, isotonicity agents, cooling agents, solvents, and pH adjusters, and does not include a thickener and/or a preservative (particularly a quaternary ammonium-based preservative (e.g., benzalkonium chloride, benzethonium chloride, etc.)).

In addition, boric acid and borax can be used as buffering agents, and the eye drop eyewash composition of the present invention may or may not contain a buffering agent other than boric acid or borax.

In addition, as one embodiment of the present invention, the eye drop-type eyewash composition of the present invention is composed of (1) at least one selected from the group consisting of chondroitin sulfate and its salts, (2) boric acid and/or borax, and (3) at least one selected from the group consisting of medicinal ingredients, stabilizers, isotonicity agents, cooling agents, solvents, and pH adjusters, without limiting the present invention.

In addition, as one embodiment of the present invention, but not limiting of the present invention, the eye drop-type eyewash composition of the present invention in each of the above embodiments is exemplified as one that does not contain an amino acid or a salt thereof, and one that does not contain an antihistamine.

The eye drop-type eyewash composition of the present invention can be produced by mixing at least one selected from the group consisting of chondroitin sulfate and its salts, boric acid and/or borax as necessary, and the other components as necessary.

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 allows use as an eye drop or eyewash, but examples of such a composition include a pH of 5 to 8, preferably a pH of 5.5 to 7.5, and more preferably a pH of 6 to 7.5 at room temperature (24°C). The pH is measured using a tabletop pH meter F-52 (manufactured by Horiba, Ltd.).

The form of the eye drop eyewash composition of the present invention is not limited, and is usually liquid at room temperature.

The eye drop type eyewash composition of the present invention is usually contained in an eye drop container and instilled in the eye, as described below. 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 at room temperature, more preferably 0.9 to 1.6 mPa·s, and even more preferably 0.9 to 1.2 mPa·s. The viscosity is measured using a cone-plate viscometer (rheometer MCR302, manufactured by Anton Paar) at a shear rate of 100 s ⁻¹ and 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 sensor is rotated at 25° C. so that the shear rate is 100 s ⁻¹ to measure the viscosity. Measurement is performed for 100 seconds, one point of data is obtained every 2 seconds, and the average value is calculated from the five data points from the 45th to 49th points, which is the viscosity.

The osmolality of the eye drop type eyewash composition of the present invention is not limited as long as it is within the range that can be used 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 measured and calculated using an automatic osmolality analyzer (OsmoStation OM-6060, manufactured by Arkray, Inc.) according to the 17th Revised Japanese Pharmacopoeia 2.47 Osmolality Measurement Method (Osmolarity Measurement Method), and is the value when the osmolarity of the composition and physiological saline (0.9 w/v% sodium chloride aqueous solution) are measured, and the measured value of physiological saline is taken as 1.

The eye drop-type eyewash composition of the present invention may be used with or without contact lenses. The contact lenses may be hard or soft contact lenses.

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.

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, and examples thereof include eye drop containers (including, for example, a container body, an inner stopper (nozzle), and a cap) used for conventionally known eye drops and eye drop-type eyewashes. The eye drop container may be of any of the following types: a type in which the container body, inner stopper (nozzle), and cap are each 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 the cap is tightened when in use to open a hole in the inner stopper (nozzle).

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 it is a multi-dose type or a unit-dose type.

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 at 4 to 8 drops per eye at one time, and more preferably 4 to 6 drops from the viewpoint of obtaining a more efficient foreign body removal effect.

The amount of the composition dispensed per drop is not limited as long as the effects of the present invention are obtained, but examples of the amount are 30 to 50 μL, preferably 35 to 40 μL, and more preferably 35 to 37 μL per drop.

There are no particular limitations on the number of times the composition is used per day, and it 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 eye can be cleaned by the eye drop-type eyewash composition of the present invention. In particular, since the composition contains at least one selected from the group consisting of chondroitin sulfate and its salts, by instilling the composition, foreign matter such as dust, pollen, protein stains, cosmetics, etc. present on the surface of the eye can be more effectively removed, thereby enhancing the eyewashing effect. Furthermore, when the composition further contains the aforementioned medicinal ingredient, it can also provide a useful effect based on the medicinal ingredient.

From this, it can be said that the present invention also provides a method for improving the foreign matter removal effect of a drop-type eyewash composition by blending at least one selected from the group consisting of chondroitin sulfate and its salts into the drop-type eyewash composition.

In this method, the eye drop type eyewash composition may further contain boric acid and/or borax, and may further contain the other components as necessary. Therefore, the present invention can be said to provide a method for improving the foreign matter removal effect of an eye drop type eyewash composition by compounding at least one selected from the group consisting of chondroitin sulfate and its salts into an eye drop type eyewash composition containing boric acid and/or borax.

In these methods, the eye drop eyewash composition, at least one selected from the group consisting of chondroitin sulfate and its salts, boric acid, borax, other components, and the contents of these components are as described above.

The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these.

Test Example
1. Preparation of eye drop type eyewash composition Each composition was prepared by mixing each component according to the mixing ratio shown in Table 1 below, and 13 mL of the composition was filled into a general eye drop container (volume 15 mL, made of polyethylene terephthalate resin, multi-dose type, manufactured by Shinko Chemical Co., Ltd.) (Examples 1 and 2 and Comparative Example 1). As the sodium chondroitin sulfate ester, non-standard sodium chondroitin sulfate (manufactured by Seikagaku Corporation, weight average molecular weight 20,000) was used.

2. Evaluation of Removal of Foreign Matter Four panelists washed their eyes using an eye cup (commercial product Eyebon Mild (manufactured by Kobayashi Pharmaceutical Co., Ltd.)) according to the instructions. Six hours after the eye washing, the area around both eyes of the four panelists was wiped clean with cleaning cotton, and the composition of Comparative Example 1 was dropped into the left eye and the composition of Example 1 was dropped into the right eye from an eye dropper, two drops each (35 μL per drop) while looking up, so that the composition did not overflow outside the eye. Next, while looking up, an eye cup was placed around each eye, and the panelists looked down while still holding the eye cup, so that the composition dropped into the eye was collected in the eye cup. The process of dropping the composition into the eye and collecting it was repeated three times in total, and a total of six drops of the composition were collected per eye. One eye cup was used per eye.

Instead of the composition of Example 1, the composition of Example 2 was used in the same manner as above, and the composition of Example 2 was also collected after a total of 6 drops were dropped per eye.

The three compositions collected in each eyecup were transferred to one eyecup and diluted with saline (containing 0.9 w/v% sodium chloride) to make 5mL, and the number of particles was counted using a particle counter (model number APSS-2000, manufactured by Particle Measuring Systems, Inc.). The number of particles with a particle size of 2 to 125 μm was regarded as the number of foreign objects, and the average number of foreign objects counted by the four subjects (average number of foreign objects) was calculated. Next, the average number of foreign objects in the composition of Comparative Example 1 was set to 100, and the average number of foreign objects in the compositions of Examples 1 and 2 was rounded off to the first decimal place for relative comparison.

3. Results The results are shown in Table 1.

As shown in Table 1, a higher foreign matter removal effect was obtained when using the compositions of Examples 1 and 2, which further contained sodium chondroitin sulfate, than when using the composition of Comparative Example 1, which did not contain sodium chondroitin sulfate.

From this, it was found that the foreign matter removal effect of the eye drop type eyewash composition can be improved by adding sodium chondroitin sulfate to the eye drop type eyewash composition. In addition, the foreign matter removal effect of the eye drop type eyewash composition prepared in the same manner as in Example 1 except that the weight average molecular weight of the sodium chondroitin sulfate was changed to 10,000 or 40,000 was higher than that of Comparative Example 1, but Example 1, which used sodium chondroitin sulfate with a weight average molecular weight of 20,000, had a particularly excellent foreign matter removal effect.

Formulation Examples Formulation examples are shown below. According to the compositions containing sodium chondroitin sulfate shown in Formulation Examples 1 to 10, the effect of removing foreign bodies from the eye was further enhanced compared to a composition having the same composition except that sodium chondroitin sulfate was not contained (substituted with water).

Claims (3)

A drop-type eyewash composition for removing foreign bodies, comprising at least one selected from the group consisting of chondroitin sulfate having a weight-average molecular weight of 15,000 to 30,000 and salts thereof as an active ingredient for removing foreign bodies ;
wherein the content of at least one selected from the group consisting of chondroitin sulfate and salts thereof in the drop-type eyewash composition is 0.01 to 0.05 w/v % in total;
The eye drop type eyewash composition is a drop type eyewash composition that is collected from the inside of the eye after being instilled in the eye.
(However, the following compositions (1) to (4) are excluded. (1) A drop-type eyewash composition containing potassium L-aspartate. (2) A drop-type eyewash composition containing chlorpheniramine maleate.
(3) Drop-type eyewash composition containing alginic acid and/or a salt thereof
(4) An eye drop type eyewash composition containing pyridoxine and/or a salt thereof . The eye drop type eyewash composition according to claim 1 further contains at least one selected from the group consisting of boric acid and borax. A method for improving a foreign matter removing effect in an eye drop type eyewash composition, comprising blending at least one selected from the group consisting of chondroitin sulfate having a weight average molecular weight of 15,000 to 30,000 and salts thereof in a total amount of 0.01 to 0.05 w/v % in the eye drop type eyewash composition ;
Here, the eye drop type eyewash composition containing at least one selected from the group consisting of chondroitin sulfate and its salts is an eye drop type eyewash composition for removing foreign matter, and is a drop type eyewash composition that is collected from the inside of the eye after being instilled in the eye.
(However, the eye drop type eyewash composition does not include the following compositions (1) to (4): (1) an eye drop type eyewash composition containing potassium L-aspartate; (2) an eye drop type eyewash composition containing chlorpheniramine maleate.
(3) Drop-type eyewash composition containing alginic acid and/or a salt thereof
(4) An eye drop type eyewash composition containing pyridoxine and/or a salt thereof .