Ophthalmic products

Abstract

To suppress a residual liquid of a content at a discharge port in an ophthalmic product.SOLUTION: An ophthalmic product including a liquid ophthalmic composition and a liquid dispensing container filled with the ophthalmic composition, wherein the liquid dispensing container includes a container body having a discharge port and a press-deformable portion and having an accommodation space for accommodating a liquid therein, and a cap, and the liquid dispensing container is configured to press and deform the press-deformable portion to discharge the ophthalmic composition from the discharge port at a constant volume, next, when the pressing force applied to the press-deformable portion is released to bring the press-deformable portion into a non-pressed state, the shape of the press-deformable portion is restored. The ophthalmic composition contains at least one selected from the group consisting of amino acids and salts thereof, mucopolysaccharides and salts thereof, water-soluble polymers, inorganic chlorides, inorganic carbonates, inorganic sulfates, and inorganic phosphates.SELECTED DRAWING: Figure 2

Description

[Technical Field]

[0001] The present invention relates to ophthalmic products. [Background technology]

[0002] Conventional eye drops are stored in a squeeze container, and when used, the eye drops are dispensed from the nozzle by squeezing the container body while the nozzle is facing the target (eyeball). However, it is difficult to determine the amount of force required to dispense each drop and the timing at which each drop is dispensed, and the reproducibility of the dispense operation is not good. Furthermore, if the amount of discharge varies when using eye drops, not only does it affect the manifestation of the medicinal effect of the eye drops, but it also changes the feeling of use each time the eye drops are applied, which is undesirable from the viewpoint of maintaining quality. Patent Document 1 describes that in eye drops with a small volume per drop (5 to 25 μL), when either a nonionic surfactant or a thickener is added alone, the volume per drop varies, but when both of these components are added simultaneously, the variation in the volume per drop is improved. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Japanese Patent Application Laid-Open No. 2014-166978 Summary of the Invention [Problem to be solved by the invention]

[0004] In the invention of Patent Document 1, the eye drops are ejected by changing the volume inside the bottle, but there is a problem that the eye drops remain around the ejection port after ejection. In particular, in ophthalmic compositions containing amino acids, mucopolysaccharides, specific inorganic salts, water-soluble polymers, etc., the components precipitate and whiten around the ejection port, which is easily noticeable. Therefore, an object of the present invention is to provide an ophthalmic product that can suppress the content from remaining on the outer surface of the discharge port. [Means for solving the problem]

[0005] The present invention has the following aspects. <1> An ophthalmic product comprising a liquid ophthalmic composition and a liquid dropper container filled with the ophthalmic composition, the liquid dripping container has a container body having a discharge port and a pressure-deformable portion, and an accommodation space for accommodating liquid therein, and a cap; the liquid dripping container is configured such that the pressure-deformed portion is pressed and deformed to discharge the ophthalmic composition at a constant volume from the discharge port, and then the pressure on the pressure-deformed portion is released to make it non-pressurized, whereby the shape of the pressure-deformed portion is restored; An ophthalmic product, wherein the ophthalmic composition comprises at least one selected from amino acids and salts thereof, mucopolysaccharides and salts thereof, water-soluble polymers, inorganic chlorides, inorganic carbonates, inorganic sulfates, and inorganic phosphates. <2> The pressure-deformation portion is formed of an elastic material, the pressure-deformable portion elastically deforms between a first position where it protrudes outward from the container body when not pressed and forms a space inside the container body that communicates with the storage space, and a second position where it is positioned closer to the storage space than the first position when pressed, and the ophthalmic composition is discharged from the discharge port due to a change in volume between the first position and the second position. <1> 1. An ophthalmic product as described in <3> a pressing force applied to the pressing and deforming portion when the ophthalmic composition is discharged from the discharge port at a constant volume is 6 N or less; <1> or <2> 1. An ophthalmic product as described in <4> The fixed volume is 5 to 50 mg. <1> ~ <3> 1. An ophthalmic product according to any one of the preceding claims. [Effects of the Invention]

[0006] According to the ophthalmic product of the present invention, it is possible to suppress the content from remaining at the discharge port. [Brief explanation of the drawings]

[0007] [Figure 1] 1 is a front view showing the liquid dripping container 1 according to the first embodiment in an upright state. [Figure 2] FIG. 2 is a vertical cross-sectional view of the liquid dripping container 1 in an upright position. [Figure 3] FIG. 2 is a right side view of the liquid dripping container 1. [Figure 4] 3 is an enlarged partial cross-sectional view of a pressure-deformed portion 30 in a non-pressed state in FIG. 2. FIG. [Figure 5] FIG. 10 is an enlarged partial cross-sectional view of a pressure-deformed portion 30 in a non-pressed state according to a second embodiment. [Figure 6] FIG. 10 is a perspective view showing a liquid dripping container 1 according to a third embodiment. [Figure 7] FIG. 10 is a front view showing the liquid dripping container 1 according to the third embodiment in an upright state. [Figure 8] 8 is an enlarged partial cross-sectional view of a protrusion 50 in FIG. 7. [Figure 9] FIG. 10 is a front view showing the liquid dripping container 1 according to the fourth embodiment in an upright state. [Figure 10] FIG. 10 is a plan view of a liquid dripping container 1 according to a fourth embodiment. [Figure 11] 10 is an enlarged partial cross-sectional view of a protrusion 50 in FIG. 9. [Figure 12] FIG. 10 is a front view showing a modified liquid dripping container 1 in an upright position. [Figure 13] 1A is a front view showing a liquid dripping container used in a comparative example, and FIG. 1B is a plan view showing a liquid dripping container used in a comparative example. DETAILED DESCRIPTION OF THE INVENTION

[0008] The following definitions of terms apply throughout the specification and claims. A numerical range expressed by "to" means that the numerical values ​​before and after "to" are the lower and upper limits of the numerical range. "Liquid ophthalmic composition" means any liquid composition related to ophthalmology, such as eye drops (synonymous with eye drops or eye drops, including eye drops that can be applied to the eyes while wearing contact lenses), artificial tears, eyewash (synonymous with eyewash or eyewash, including eyewash that can be applied to the eyes while wearing contact lenses), contact lens wetting solution, contact lens removal solution, or contact lens care products (including disinfectants, preservatives, cleaners, etc.). "Water-soluble" means that the solubility in 1 L of water at 25°C is 0.1 g or more. The unit of content (concentration) of each component, "w / v%," stands for "mass / volume %," and represents the mass (g) of the compounded component contained in 100 mL of the ophthalmic composition, and is synonymous with "g / 100 mL."

[0009] The ophthalmic product of the present invention comprises a liquid ophthalmic composition and a liquid dropper container filled with the ophthalmic composition.

[0010] (Ophthalmic composition) The ophthalmic composition of the present invention is a liquid composition containing component (A). In the following description, the unit of content, "%", is "w / v (mass / volume)%" unless otherwise specified.

[0011] <Component (A)> Component (A) is at least one selected from amino acids and their salts, mucopolysaccharides and their salts, water-soluble polymers, and specific inorganic salts. When the ophthalmic composition contains component (A), it can exhibit pharmacological effects, etc. In addition, when the ophthalmic composition contains component (A), whitening is likely to occur if any liquid remains around the discharge port.

[0012] <(a1) Component: Amino acid and its salt> Examples of amino acids and salts thereof (component (a1)) include potassium L-aspartate, magnesium L-aspartate, potassium and magnesium L-aspartate (equal mixture), aminoethylsulfonic acid (taurine), epsilon-aminocaproic acid, etc. Among these, potassium L-aspartate and aminoethylsulfonic acid (taurine) are preferred as component (a1) from the viewpoints of better exerting the effects of the present invention and further enhancing pharmacological effects (such as promoting metabolism and bringing oxygen to the eyes). The component (a1) may be one type alone or a combination of two or more types.

[0013] The content of the component (a1) is determined appropriately taking into consideration the type of the component (a1) and the like, and is, for example, preferably 0.03 to 5%, more preferably 0.1 to 3%, of the total volume of the ophthalmic composition. When the component (a1) is potassium L-aspartate, the content of the component (a1) is preferably 0.03 to 5%, and more preferably 0.2 to 3%, relative to the total volume of the ophthalmic composition. When the component (a1) is aminoethylsulfonic acid (taurine), the content of the component (a1) is preferably 0.03 to 5%, and more preferably 0.1 to 1%, based on the total volume of the ophthalmic composition. When the content of component (a1) is equal to or greater than the lower limit, the effects of the present invention are more readily exhibited, and the pharmacological effect of component (a1) is further enhanced.When the content of component (a1) is equal to or less than the upper limit, the residue of the contents on the outer surface of the discharge port is further suppressed, and irritation caused by the ophthalmic composition is further suppressed.

[0014] <(a2) Ingredient: Mucopolysaccharides and their salts> Examples of mucopolysaccharides and salts thereof (component (a2)) include chondroitin sulfate and salts thereof, and hyaluronic acid and salts thereof. In terms of enhancing the effects of the present invention, sodium chondroitin sulfate and sodium hyaluronate are preferred as component (a2). The component (a2) may be one type alone or a combination of two or more types.

[0015] The chondroitin sulfate and its salts are not particularly limited, and any chondroitin sulfate esters commonly used in ophthalmic compositions can be used, including chondroitin sulfate esters and their pharmaceutically and physiologically acceptable salts. Specific examples include chondroitin sulfate, chondroitin polysulfate, and sodium chondroitin sulfate, with sodium chondroitin sulfate being preferred. The weight-average molecular weight of chondroitin and its salts is preferably 5,000 to 100,000, more preferably 7,000 to 50,000. The weight-average molecular weight is measured by gel permeation chromatography. Commercially available products include non-standard sodium chondroitin sulfate manufactured by Maruha Nichiro Corporation, non-standard sodium chondroitin sulfate manufactured by Seikagaku Corporation, and non-standard sodium chondroitin sulfate manufactured by Nippon Biocon Co., Ltd.

[0016] Hyaluronic acid and its salt are not particularly limited, and can be used any hyaluronic acid that is generally used in ophthalmic compositions, and include hyaluronic acid and its pharmaceutically and physiologically acceptable salt.Can be used by the method of extracting from cockscomb, the method of fermentation by microorganism, etc., and its origin and manufacturing method are not particularly limited. The hyaluronic acid and its salts can be used singly or in appropriate combination of two or more kinds. Specific examples include hyaluronic acid, sodium hyaluronate, potassium hyaluronate, magnesium hyaluronate, calcium hyaluronate, etc. Among these, sodium hyaluronate is preferred. The viscosity average molecular weight of hyaluronic acid and its salts is preferably 100,000 to 5,000,000, more preferably 200,000 to 4,000,000, even more preferably 300,000 to 2,500,000, particularly preferably 400,000 to 2,000,000, and most preferably 500,000 to 1,490,000. Viscosity average molecular weight is measured by the viscosity average molecular weight measurement method described in "purified sodium hyaluronate" in the Japanese Pharmacopoeia, 18th Edition, Pharmaceuticals Articles.In addition, the viscosity average molecular weight of hyaluronic acid or its salt in ophthalmic composition is measured by the viscosity average molecular weight measurement method described in "purified sodium hyaluronate ophthalmic solution" in the Japanese Pharmacopoeia, 18th Edition.In addition, multiple kinds of hyaluronic acid or its salt with different viscosity average molecular weight can be used. Commercially available products include "Sodium Hyaluronate "Seikagaku"" (viscosity average molecular weight 500,000 to 1.2 million) manufactured by Seikagaku Corporation, and "Hyaluronic Acid FCH-60" (viscosity average molecular weight 500,000 to 700,000), "Hyaluronic Acid FCH-80" (viscosity average molecular weight 600,000 to 1 million), "Hyaluronic Acid FCH-120" (viscosity average molecular weight 1 million to 1.4 million), "Hyaluronic Acid FCH-150" (viscosity average molecular weight 1.4 million to 1.8 million), "Hyaluronic Acid FCH-151C" (viscosity average molecular weight 1.4 million to 1.8 million), "Hyaluronic Acid FCH-200" (viscosity average molecular weight 1.8 million to 2.2 million), "Hyaluronic Acid FCH-201C" (viscosity average molecular weight 1.8 million to 2.2 million), and "Hyaluronic Acid FCH-80LE" ( Examples include "Hyaluronic Acid GS-100" (viscosity average molecular weight 500,000 to 1,490,000), "Hyaluronic Acid HA-QA" (viscosity average molecular weight 600,000 to 1,200,000), "Hyaluronic Acid HA-AM" (viscosity average molecular weight 600,000 to 1,200,000), "Hyaluronic Acid HA-Q" (viscosity average molecular weight 530,000 to 1,130,000), "Hyaluronic Acid M5070" (viscosity average molecular weight 500,000 to 700,000), "Hyaluronic Acid HA-LQ" (viscosity average molecular weight 850,000 to 1,600,000), "Hyaluronic Acid HA-LQH" (viscosity average molecular weight 1,200,000 to 2,200,000), "Hyaluronic Acid HA-AML" (viscosity average molecular weight 500,000 to 1,200,000), and "Hyaluronic Acid HA-SHL" (viscosity average molecular weight 1,600,000 to 2,400,000).

[0017] The content of the component (a2) is determined appropriately taking into consideration the type of the component (a2) and the like, and is, for example, preferably 0.001 to 3%, more preferably 0.01 to 1%, of the total volume of the ophthalmic composition. When the component (a2) is sodium chondrotin sulfate, the content of the component (a2) is preferably 0.01 to 3%, and more preferably 0.03 to 1%, based on the total volume of the ophthalmic composition. When the component (a2) is sodium hyaluronate, the content of the component (a2) is preferably 0.001 to 1%, and more preferably 0.01 to 0.2%, relative to the total volume of the ophthalmic composition. When the content of component (a2) is equal to or greater than the lower limit, the effects of the present invention are more readily exhibited, and the pharmacological effect of component (a2) is further enhanced.When the content of component (a2) is equal to or less than the upper limit, the residue of the contents on the outer surface of the discharge port is further suppressed, and the sticky feeling when the ophthalmic composition is instilled into the eye is further suppressed.

[0018] ≪(a3) Component: Water-soluble polymer≫ Examples of the water-soluble polymer (component (a3)) include polyvinylpyrrolidone, hydroxypropyl cellulose, hydroxypropylmethyl cellulose (hypromellose), hydroxyethyl cellulose, methyl cellulose, polyvinyl alcohol, and carboxyvinyl polymer. Among these, hydroxypropylmethylcellulose and polyvinylpyrrolidone are preferred in terms of the effects of the present invention being more pronounced. The component (a3) ​​may be one type alone or a combination of two or more types.

[0019] The polyvinylpyrrolidone is not particularly limited, and it is preferable to use polyvinylpyrrolidone (povidone) listed in the 18th edition of the Japanese Pharmacopoeia. The K value is preferably 10 to 120, and can be determined by the method described in the 18th edition of the Japanese Pharmacopoeia. Examples of polyvinylpyrrolidone include those with a K value of 11 to 14 (e.g., Kollidon 12PF (manufactured by BASF Japan Ltd.)), those with a K value of 16 to 18 (e.g., Kollidon 17PF (manufactured by BASF Japan Ltd.)), those with a K value of 28 to 32 (e.g., Kollidon 30 (manufactured by BASF Japan Ltd.)), and those with a K value of 85 to 95 (e.g., Kollidon 90F (manufactured by BASF Japan Ltd.)). Polyvinylpyrrolidone (K90) with a K value of 85 to 95 is preferred.

[0020] There are no particular limitations on the hydroxypropyl cellulose, and one with a viscosity of 100 to 5,000 mPa·s in a 2% aqueous solution can be suitably used. For example, the product name "NISSO HPC M" available from Nippon Soda Co., Ltd. can be used.

[0021] The hydroxypropyl methylcellulose is not particularly limited, and it is preferable to use hydroxypropyl methylcellulose (hypromellose) listed in the 18th edition of the Japanese Pharmacopoeia. The degree of substitution type may be any of 2910, 2906, 2208, and 1828, with 2910, 2906, and 2208 being preferred. Examples of 2910 include those having a viscosity of 40.0 to 60.0 mPa·s in a 2 w / v% aqueous solution (e.g., METLOSE 60SH50 (manufactured by Shin-Etsu Chemical Co., Ltd.)), those having a viscosity of 3,000 to 5,600 mPa·s (e.g., METLOSE 60SH4000 (manufactured by Shin-Etsu Chemical Co., Ltd.)), and those having a viscosity of 7,500 to 14,000 mPa·s (e.g., METLOSE 60SH10000 (manufactured by Shin-Etsu Chemical Co., Ltd.)). Examples of 2906 include those having a viscosity of 40.0 to 60.0 mPa·s in a 2 w / v% aqueous solution (for example, METLOSE 65SH50 (manufactured by Shin-Etsu Chemical Co., Ltd.)), those having a viscosity of 320 to 480 mPa·s (for example, METLOSE 65SH400 (manufactured by Shin-Etsu Chemical Co., Ltd.)), and those having a viscosity of 3,000 to 5,600 mPa·s (for example, METLOSE 65SH4000 (manufactured by Shin-Etsu Chemical Co., Ltd.)). Examples of 2208 include those having a viscosity of 80 to 120 mPa·s in a 2 w / v% aqueous solution (for example, METLOSE 90SH-SR100 (manufactured by Shin-Etsu Chemical Co., Ltd.)) and those having a viscosity of 3,000 to 5,600 mPa·s (for example, METLOSE 90SH-SR4000 (manufactured by Shin-Etsu Chemical Co., Ltd.)). The viscosity of component (C) should be measured according to Method 1 (20°C) of the 18th Edition of the Japanese Pharmacopoeia if it is less than 600 mPa·s, and according to Method 2 (20°C) if it is 600 mPa·s or greater. Among these hydroxypropyl methylcelluloses, those having a degree of substitution of 2910 and a viscosity of a 2 w / v % aqueous solution of 3,000 to 5,600 mPa·s are preferred in terms of obtaining the effects of the present invention more effectively.

[0022] There are no particular limitations on the hydroxyethyl cellulose, and it is preferable to use hydroxyethyl cellulose (hydroxyethoxyl groups: 30.0 to 70.0%) listed in the Pharmaceutical Excipients Standards 2018. Examples of hydroxyethyl cellulose include those having a viscosity of 300 to 600 mPa·s in a 2 w / v% aqueous solution (e.g., HEC CF-G (Sumitomo Seika Chemicals Co., Ltd.)), those having a viscosity of 5,000 to 10,000 mPa·s in a 2 w / v% aqueous solution (e.g., HEC CF-V (Sumitomo Seika Chemicals Co., Ltd.)), those having a viscosity of 10,000 to 16,000 mPa·s in a 2 w / v% aqueous solution (e.g., HEC CF-W (Sumitomo Seika Chemicals Co., Ltd.)), those having a viscosity of 1,250 to 1,750 mPa·s in a 1 w / v% aqueous solution (e.g., HEC CF-X (Sumitomo Seika Chemicals Co., Ltd.)), and those having a viscosity of 2,000 to 3,000 mPa·s in a 1 w / v% aqueous solution (e.g., HEC CF-Y (Sumitomo Seika Chemicals Co., Ltd.)).

[0023] There are no particular limitations on the methylcellulose, and it is preferable to use methylcellulose (26.0 to 33.0% methoxy groups) listed in the 18th edition of the Japanese Pharmacopoeia. Examples of methylcellulose include those having a viscosity of 3.2 to 4.8 mPa·s in a 2 w / v% aqueous solution (e.g., METLOSE SM4 (manufactured by Shin-Etsu Chemical Co., Ltd.)), those having a viscosity of 12.0 to 18.0 mPa·s (e.g., METLOSE SM15 (manufactured by Shin-Etsu Chemical Co., Ltd.)), those having a viscosity of 20.0 to 30.0 mPa·s (e.g., METLOSE SM25 (manufactured by Shin-Etsu Chemical Co., Ltd.)), those having a viscosity of 80 to 120 mPa·s (e.g., METLOSE SM100 (manufactured by Shin-Etsu Chemical Co., Ltd.)), those having a viscosity of 320 to 480 mPa·s (e.g., METLOSE SM400 (manufactured by Shin-Etsu Chemical Co., Ltd.)), and those having a viscosity of 1,125 to 2,100 mPa·s (e.g., METLOSE SM1500 (manufactured by Shin-Etsu Chemical Co., Ltd.)), and a viscosity of 3,000 to 5,600 mPa·s (for example, METLOSE SM4000 (manufactured by Shin-Etsu Chemical Co., Ltd.)).

[0024] The polyvinyl alcohol is not particularly limited, but the saponification degree of the polyvinyl alcohol is preferably 78 to 96 mol% and the viscosity of a 4% aqueous solution (20°C) is preferably 3 to 60 mm 2 Commercially available polyvinyl alcohols can be used, for example, polyvinyl alcohol: GOHSENOL EG-03P, manufactured by Mitsubishi Chemical Corporation (saponification degree: 86.5 to 89.0 mol%, viscosity of 4% aqueous solution (20°C): 3.0 to 3.8 mm 2 / s), polyvinyl alcohol: GOHSENOL EG-05P, manufactured by Mitsubishi Chemical Corporation (saponification degree: 86.5 to 89.0 mol%, viscosity of 4% aqueous solution (20°C): 4.5 to 6.1 mm) 2 / s), polyvinyl alcohol: GOHSENOL EG-18P, manufactured by Mitsubishi Chemical Corporation (saponification degree: 86.5 to 89.0 mol%, viscosity of 4% aqueous solution (20°C): 15.3 to 20.7 mm) 2 / s), polyvinyl alcohol: GOHSENOL EG-22P, manufactured by Mitsubishi Chemical Corporation (saponification degree: 86.5 to 89.0 mol%, viscosity of 4% aqueous solution (20°C): 19.0 to 25.6 mm)2 / s), polyvinyl alcohol: GOHSENOL EG-30P, manufactured by Mitsubishi Chemical Corporation (saponification degree: 86.5 to 89.0 mol%, viscosity of 4% aqueous solution (20°C): 25.5 to 34.5 mm) 2 / s), polyvinyl alcohol: GOHSENOL EG-40P, manufactured by Mitsubishi Chemical Corporation (saponification degree: 86.5 to 89.0 mol%, viscosity of 4% aqueous solution (20°C): 36.6 to 49.4 mm 2 / s), polyvinyl alcohol: GOHSENOL EG-48P, manufactured by Mitsubishi Chemical Corporation (saponification degree: 86.5 to 89.0 mol%, viscosity of 4% aqueous solution (20°C): 41.3 to 55.7 mm) 2 / s) etc. The viscosity is measured according to Method 1 of the 18th Edition of the Japanese Pharmacopoeia (20°C).

[0025] The carboxyvinyl polymer preferably has a viscosity (measured by a BH-type rotational viscometer, concentration 0.2% by mass, rotor No. 7, rotation speed 20 rpm, 25°C) in the range of 3,000 to 80,000 mPa·s, and more preferably 5,000 to 50,000 mPa·s. The carboxyvinyl polymer also includes its salts. Commercially available products include Carbopol 914, 934, 934P, 971P, 974P, 980, 981, 2984, 5984, ETD2050, and Ultrez10 (manufactured by Lubrizol Corporation), Juron PW-110, PW-111, PW-150, PW-302, PW-310, and PW-350 (manufactured by Toagosei Co., Ltd.), Hiviswako 103, 104, and 105 (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.), and AQUPEC HV-501, HV-504, and HV-505 (manufactured by Sumitomo Seika Chemicals Co., Ltd.), and one or more of these may be used.

[0026] The content of component (a3) ​​is preferably 0.05 to 5%, more preferably 0.1 to 3%, and even more preferably 0.2 to 1%, of the total volume of the ophthalmic composition. By ensuring that the content of component (a3) ​​is at least the above-mentioned lower limit, the effects of the present invention are more easily achieved, and the moist feeling and tear stabilization effects are further enhanced. By ensuring that the content of component (a3) ​​is at most the above-mentioned upper limit, residual liquid of the contents on the outer surface of the ejection port is further suppressed, and variation in the volume of each drop can be further reduced.

[0027] ≪(a4) component≫ The specific inorganic salt (component (a4)) is at least one selected from inorganic chlorides, inorganic carbonates, inorganic sulfates, and inorganic phosphates. Examples of inorganic chlorides include sodium chloride, potassium chloride, calcium chloride, magnesium chloride, and zinc chloride. Examples of inorganic carbonates include sodium bicarbonate and sodium carbonate. Examples of inorganic sulfates include magnesium sulfate and zinc sulfate. Examples of inorganic phosphates include sodium hydrogen phosphate, sodium dihydrogen phosphate, and potassium dihydrogen phosphate. The component (a4) may be an anhydride or a hydrate. These components (a4) may be used alone or in combination of two or more.

[0028] The content of component (a4) is preferably 0.001 to 5%, and more preferably 0.01 to 1%, of the total volume of the ophthalmic composition. When the content of component (a4) is within the above range, the content is further prevented from remaining on the outer surface of the discharge port, and eye irritation when the ophthalmic composition is instilled is further reduced.

[0029] The above-mentioned component (A) may be used alone or in combination of two or more.

[0030] <Optional ingredients> The ophthalmic composition may contain any optional components other than component (A). Optional ingredients include water, drugs (excluding component (A)), nonionic surfactants, oily ingredients, local anesthetics or soothing agents, preservatives, sugars, buffers, pH adjusters, isotonicity agents, stabilizers, cooling agents, polyhydric alcohols, thickeners (excluding component (A)), etc.

[0031] The ophthalmic composition of the present invention is preferably an aqueous ophthalmic composition. Here, the term "aqueous ophthalmic composition" refers to an ophthalmic composition whose medium is water. The water used in the ophthalmic composition is not particularly limited as long as it is medicamentarily, pharmacologically or physiologically acceptable, and examples thereof include purified water and sterilized water. The content of water in the ophthalmic composition is preferably 90 to 99.9%, more preferably 93 to 98%. Preferred examples of aqueous ophthalmic compositions include eye drops (including eye drops that can be applied while wearing contact lenses), artificial tears, eyewashes (including eyewashes that can be used to wash the eyes while wearing contact lenses), contact lens wetting solutions, and contact lens removal solutions, with eye drops being particularly preferred. Contact lenses include, but are not limited to, hard contact lenses (including O2 hard contact lenses), soft contact lenses (including both ionic and non-ionic), silicone hydrogel contact lenses, colored contact lenses, etc. When no preservative is added, the composition is particularly suitable for use with soft contact lenses and silicone hydrogel contact lenses.

[0032] Examples of drugs (optional drugs) other than those listed in component (A) include decongestant ingredients (e.g., epinephrine, epinephrine hydrochloride, ephedrine hydrochloride, naphazoline hydrochloride, naphazoline nitrate, phenylephrine hydrochloride, dl-methylephedrine hydrochloride, tetrahydrozoline hydrochloride, etc.), anti-inflammatory / astringent agents (e.g., dipotassium glycyrrhizinate, berberine chloride, berberine sulfide, allantoin, sodium azulene sulfonate, zinc sulfate, zinc lactate, lysozyme hydrochloride, etc.), antihistamines (chlorpheniramine maleate, diphenhydramine hydrochloride, etc.), oil-soluble vitamins (vitamin A, for example, in addition to vitamin A itself, vitamin A-containing mixtures such as vitamin A oil, vitamin A derivatives such as vitamin A fatty acid esters, specifically, retinol palmitate, retinol ester ... Vitamin E, such as d-α-tocopherol, dl-α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol, and mixed tocopherols, and derivatives thereof include tocopherol acetate (vitamin E acetate), vitamin E nicotinate, vitamin E succinate, and vitamin E linolenate), water-soluble vitamins (vitamin B such as flavin adenine dinucleotide sodium, cyanocobalamin, pyridoxine hydrochloride, panthenol, calcium pantothenate, and sodium pantothenate; vitamin C such as sodium ascorbate), and sulfonamides (sulfamethoxazole, sulfisoxazole, and salts thereof). These optional drugs may be used alone or in combination of two or more. The content of the optional drug is determined appropriately taking into consideration the type of the optional drug, etc. When an optional drug is incorporated, the content is preferably 0.001 to 5%, more preferably 0.001 to 1%, and even more preferably 0.001 to 0.1%, relative to the total volume of the ophthalmic composition.

[0033] Examples of nonionic surfactants include polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene polyoxypropylene glycol, and polyethylene glycol fatty acid ester. These nonionic surfactants may be used alone or in combination of two or more. When a nonionic surfactant is added, its content is preferably 0.02 to 3% based on the total volume of the ophthalmic composition.

[0034] Examples of oily components include sesame oil, castor oil, liquid paraffin, paraffin, soybean oil, olive oil, corn oil, coconut oil, almond oil, peanut oil, wheat germ oil, rapeseed oil, sunflower oil, refined lanolin, white lanolin, gel hydrocarbon, medium-chain fatty acid triglyceride, white petrolatum, wax ester, and sterol ester, etc. In terms of better exerting the effects of the present invention, one or more selected from liquid paraffin, sesame oil, and castor oil are preferred. These oily components may be used alone or in combination of two or more. When an oily component is incorporated, the content thereof is preferably 0.0001 to 0.5% relative to the total volume of the ophthalmic composition.

[0035] Examples of local anesthetics or soothing agents include chlorobutanol, oxybuprocaine hydrochloride, dibucaine hydrochloride, tetracaine hydrochloride, piperocaine hydrochloride, procaine hydrochloride, proparacaine hydrochloride, hexothiocaine hydrochloride, lidocaine hydrochloride, etc. When a local anesthetic or soothing agent is added, its content is preferably 0.001 to 1%, and more preferably 0.01 to 0.5%, relative to the total volume of the ophthalmic composition. Examples of preservatives include chlorhexidine gluconate, chlorobutanol, benzalkonium chloride, etc. When a preservative is added, the content is preferably 0.00005 to 0.2%, more preferably 0.0001 to 0.1%, relative to the total volume of the ophthalmic composition. Examples of sugars include glucose, cyclodextrin, xylitol, sorbitol, and mannitol. Sugars have moisturizing properties and can increase the moisture content of the eye drops when applied to the eye, and can also be used as an isotonic agent. When sugars are added, the content is preferably 0.001 to 5%, and more preferably 0.003 to 2%, of the total volume of the ophthalmic composition. Examples of the buffering agent include boric acid, borax, trometamol, ethylenediamineacetic acid derivatives or salts thereof, and the like. When a buffering agent is incorporated, the content of the buffering agent is preferably 0.001 to 5%, more preferably 0.01 to 4%, and even more preferably 0.1 to 3%, based on the total volume of the ophthalmic composition. Examples of the isotonic agent include the sugars described above and the polyhydric alcohols described below. Examples of stabilizers include cyclodextrin and monoethanolamine. Examples of fat-soluble stabilizers (antioxidants) include dibutylhydroxytoluene (BHT) and butylhydroxyanisole (BHA). Examples of water-soluble stabilizers (antioxidants) include sulfites such as sodium sulfite, potassium sulfite, dry sodium sulfite (anhydrous sodium sulfite), sodium pyrosulfite, potassium pyrosulfite, sodium bisulfite, and potassium bisulfite, ascorbic acid, and sodium ascorbate. When these stabilizers are incorporated, their content is preferably 0.001 to 2%, and more preferably 0.003 to 1%, of the total volume of the ophthalmic composition. Examples of refreshing agents include menthol, geraniol, cineole, linalool, anethole, eugenol, limonene, and rhubarb. They may be in the d-, l-, or dl-isomer. Other examples include essential oils such as peppermint oil, cool mint oil, spearmint oil, peppermint oil, eucalyptus oil, rose oil, fennel oil, bergamot oil, and cinnamon oil. These refreshing agents can enhance the perceived effect of sustained moisture. When a refreshing agent or essential oil is incorporated, its content is preferably 0.0005 to 0.2%, more preferably 0.0001 to 0.1%, based on the total volume of the ophthalmic composition. Examples of polyhydric alcohols include glycerin, propylene glycol, butylene glycol, and polyethylene glycol. Polyhydric alcohols have moisturizing properties, which enhance the moisturizing effect of the eye drops when applied, and they can also be used as isotonic agents. Glycerin and propylene glycol can also be used as solubilizers for cooling agents. When polyhydric alcohols are incorporated, their content is preferably 0.001 to 5%, more preferably 0.003 to 1%, of the total volume of the ophthalmic composition. These components may be used alone or in combination of two or more.

[0036] Examples of pH adjusters include inorganic acids and inorganic alkali agents. Examples of inorganic acids include (dilute) hydrochloric acid. Examples of inorganic alkali agents include sodium hydroxide, potassium hydroxide, sodium carbonate, and sodium bicarbonate. An appropriate amount is added to achieve the desired pH.

[0037] <ph> The pH of the ophthalmic composition of the present invention at 25° C. is preferably 3.5 to 8.0, more preferably 4.0 to 7.8, and particularly preferably 5.0 to 7.5. The pH of the ophthalmic composition can be measured at 25° C. using a pH meter, for example, HM-25R, manufactured by DKK-Toa Corporation.

[0038] <Viscosity> The viscosity of the ophthalmic composition of the present invention at 25°C is preferably 1.1 to 50 mPa·s, more preferably 1.1 to 40 mPa·s, even more preferably 1.1 to 30 mPa·s, still more preferably 1.1 to 20 mPa·s, still more preferably 1.1 to 15 mPa·s, still more preferably 1.1 to 12 mPa·s, particularly preferably 1.1 to 10 mPa·s, and most preferably 1.1 to 8 mPa·s. The viscosity of the ophthalmic composition is a value measured at 25°C using a B-type rotational viscometer in accordance with the method specified in the "Viscosity Measurement Method" section of the "General Test Methods" section of the "2nd Rotational Viscometer Method" in the "General Test Methods" section of the "Cone-Plate Viscometer" section of the "Cone-Plate Viscometer" section of the "General Test Methods" section of the "Japanese Pharmacopoeia, 18th Edition." The conditions for the measurement, such as the rotor and rotation speed, are selected depending on the viscosity range.

[0039] <Efficacy> The ophthalmic composition of the present invention can be used in artificial tears having the effects and efficacy of relieving eye fatigue, lacrimal supplementation (dry eyes), discomfort when wearing soft or hard contact lenses, eye fatigue, blurred vision (when there is a lot of eye discharge, etc.), etc., over-the-counter eye drops having the effects and efficacy of relieving eye fatigue, blurred vision (when there is a lot of eye discharge, etc.), conjunctival congestion, itchy eyes, blepharitis (sore eyelids), prevention of eye diseases (after swimming, when dust or sweat gets into the eyes, etc.), ophthalmia caused by ultraviolet rays or other light (snow blindness, etc.), discomfort when wearing hard contact lenses, etc., and antibacterial eye drops having the effects and efficacy of relieving conjunctivitis (pink eye), styes, blepharitis (sore eyelids), itchy eyes, etc. It can also be used as a contact lens wetting solution that makes it easier to wear hard or soft contact lenses.

[0040] <Dosage> When the ophthalmic composition of the present invention is used as an eye drop, it is preferably administered in the form of 1 to 3 drops of 5 to 50 mg each time, 1 to 6 times per day, more preferably 1 to 3 drops of 10 to 40 mg each time, 1 to 6 times per day, and even more preferably 1 to 3 drops of 10 to 30 mg each time, 1 to 6 times per day. Furthermore, when used as a contact lens wetting solution, it is preferable to wet both surfaces of a contact lens with 1 to 2 drops of the ophthalmic composition before wearing the lens, or to wet the lens with 1 to 2 drops, rinse the lens with water once, and then apply 1 drop to the inner surface of the lens before wearing the lens.

[0041] <Manufacturing method> The ophthalmic composition of the present invention can be obtained by mixing the components contained in the ophthalmic composition by a known method. When the ophthalmic composition is an aqueous ophthalmic composition, an example of a production method is to dissolve component (A) and any necessary optional components in part of water, then adjust the pH, and then add the remainder of the water to obtain the ophthalmic composition. When an oily component is added, it is preferable to prepare a mixture by mixing the oily component with a nonionic surfactant, and then add the mixture before adjusting the pH.

[0042] (liquid drip container) Hereinafter, an embodiment of a liquid dripping container will be described with reference to the drawings. Note that the following embodiment shows one aspect of the present invention, does not limit the present invention, and can be modified as desired within the scope of the technical concept of the present invention. In addition, in the following drawings, the scale and number of each structure are different from the actual structure to make each component easier to understand.

[0043] The liquid dropping container of the present invention comprises a container body having a discharge port and a pressure-deformable portion, and a cap. The liquid dropping container can dispense the ophthalmic composition at a constant volume by pressing the pressure-deformable part. Note that "constant volume" means that the amount dispensed by standard operation is ±10% of the designed amount.

[0044] <First embodiment of liquid dripping container> Figures 1 to 3 show a first embodiment of a liquid dripping container. Figure 1 is a front view showing a liquid dripping container 1 in an upright position according to the first embodiment. Figure 2 is a vertical cross-sectional view of the liquid dripping container 1 in an upright position. Figure 3 is a right side view of the liquid dripping container 1.

[0045] 1 to 3, the liquid dripping container 1 is a generally rectangular cylindrical container that extends vertically in an upright position and tapers toward the top. The liquid dripping container 1 has a storage space 1A therein for storing a liquid. A liquid ophthalmic composition is stored in the storage space 1A.

[0046] The up-down direction in the following description refers to the direction when the liquid dripping container 1 is placed and in an upright position, and does not limit the direction when the liquid is dripping. The horizontal direction in the front view shown in Figure 1 is called the width direction. The depth direction perpendicular to the paper surface in the front view shown in Figure 1 is called the thickness direction.

[0047] The liquid dripping container 1 has a container body 10, a discharge port 20, a pressure-deformable portion 30, and a cap 40. The container body 10 has a lower body 12 and an inner plug member 14 . The lower body 12 has a cylindrical shape with a bottom 13 on the lower side and an open top. The lower body 12 has a rectangular cylindrical shape that is open top. The lower body 12 has a fitting recess 12a. The fitting recess 12a is a recess formed on the inner surface of the lower body 12 and recessed from the upper end. The fitting recess 12a is formed around the entire periphery of the inner surface at the upper end of the lower body 12.

[0048] The material of the lower body 12 is not particularly limited, but it is preferable that the material has a strength that makes it difficult for deformation (squeezing) to occur when pressed in the thickness direction. Examples of materials for the lower body 12 having the above strength include polyethylene terephthalate resin (PET), polybutylene terephthalate resin (PBT), high-density polyethylene resin (HDPE), low-density polyethylene resin (LDPE), polypropylene resin (PP), or glass. Since foreign object inspection may be performed after the storage space 1A is filled with liquid, it is preferable that the lower body 12 be made of a transparent material that allows foreign object inspection. Furthermore, polyethylene terephthalate resin (PET) is more preferable in terms of the stability over time of the liquid stored in the storage space 1A and the impact resistance of the container body.

[0049] The inner plug member 14 has an inclined wall 15 and a curved wall 16 on the upper side, and is tubular with a rectangular cross section perpendicular to the vertical direction that opens downward. The inclined wall 15 is disposed to the left in the width direction of the center of the inside plug member 14. The inclined wall 15 is linearly inclined downward as it moves leftward. The curved wall 16 is disposed to the right in the width direction of the inclined wall 15 of the inside plug member 14. The curved wall 16 is curved in an arc shape downward as it moves to the right.

[0050] The inside plug member 14 has a fitting protrusion 14a. The fitting protrusion 14a protrudes downward from the inner surface at the lower end of the inside plug member 14. The fitting protrusion 14a is formed around the entire circumference of the lower end of the inside plug member 14. The fitting protrusion 14a fits into the fitting recess 12a of the lower main body 12 from the inside in the width direction and thickness direction around the entire circumference. By fitting the fitting protrusion 14a into the fitting recess 12a, the inside plug member 14 is fixed to the lower main body 12, and a storage space 1A is formed between the inside plug member 14 and the lower main body 12.

[0051] The material of the inside plug member 14 is not particularly limited, but it is preferable that the material has a strength that makes it difficult for deformation (squeezing) to occur when pressed in the thickness direction. Examples of materials for the inner plug member 14 having the above strength include polyethylene terephthalate resin (PET), polybutylene terephthalate resin (PBT), high-density polyethylene resin (HDPE), low-density polyethylene resin (LDPE), and polypropylene resin (PP), with high-density polyethylene resin (HDPE), low-density polyethylene resin (LDPE), and polypropylene resin (PP) being more preferred.

[0052] The discharge port 20 is provided in the inclined wall 15 of the inside plug member 14. The discharge port 20 extends in a direction perpendicular to the inclined wall 15. 2, the discharge port 20 has a discharge flow path 21. The discharge flow path 21 extends in a direction perpendicular to the inclined wall 15 and penetrates the discharge port 20. One end of the discharge flow path 21 communicates with the accommodation space 1A and the other end opens to the outside.

[0053] The inner diameter of the ejection port 20 (outer diameter of the ejection flow path 21) is set from the viewpoint of controlling the amount of one droplet of liquid. Specifically, the inner diameter of the ejection port 20 is set to a value such that, when the ejection port 20 faces downward and the liquid in the storage space 1A is in contact with the ejection flow path 21, the surface tension of the liquid becomes greater than the ejection force due to the weight of the liquid when the storage space 1A is at atmospheric pressure, and the liquid is not ejected from the ejection port 20.

[0054] Furthermore, when the pressure in the storage space 1A is greater than atmospheric pressure by a predetermined amount, the inner diameter of the discharge port 20 becomes larger than the surface tension of the liquid, and the liquid is discharged in the discharge direction 20A, which is the direction in which the discharge flow path 21 extends from the discharge port 20, and is set to a diameter that allows one droplet of liquid to be dropped. The inner diameter of the discharge port 20 is preferably 2.0 mm or less, taking into consideration the surface tension of the liquid. The lower limit of the inner diameter of the discharge port 20 is preferably 0.5 mm or more. When the inner diameter of the discharge port 20 is equal to or greater than the lower limit, the ophthalmic composition is quickly discharged at a constant volume, and the shape of the pressure-deformed portion is more quickly restored when the pressure on the pressure-deformed portion is released. When the shape of the discharge port 20 is polygonal, the inner diameter of the discharge port 20 is the diameter of the circumscribing circle of the discharge port 20.

[0055] The discharge port 20 may be a molded body integrally formed with the inner plug member 14, or may be formed as a separate member made of a material different from that of the inner plug member 14. If the discharge outlet 20 is a separate component from the inner plug member 14, a process of attaching the discharge outlet 20 to the inner plug member 14 is required, which is time-consuming during manufacturing. Therefore, from the standpoint of manufacturing efficiency, it is preferable that the discharge outlet 20 be a molded body that is integrally molded from the same material as the inner plug member 14.

[0056] Examples of materials for the outlet 20 include polyethylene terephthalate resin (PET), polybutylene terephthalate resin (PBT), high-density polyethylene resin (HDPE), low-density polyethylene resin (LDPE), and polypropylene resin (PP), with high-density polyethylene resin (HDPE), low-density polyethylene resin (LDPE), and polypropylene resin (PP) being more preferred.

[0057] The cap 40 is detachably fitted to the upper side of the container body 10. The cap 40 has a top and is a rectangular cylindrical shape that is open to the bottom. The cap 40 is fitted onto the container body 10 from above, covering both sides in the width direction and thickness direction as well as the top side of the container body 10. The lower end of the cap 40 is located below the lower end of the inner plug member 14. In other words, when attached to the container body 10, the cap 40 covers the inner plug member 14 and fits into the lower body 12.

[0058] The press-deformation portion 30 is provided on the curved wall 16 of the inner plug member 14. The press-deformation portion 30 is provided away from the discharge port 20. The press-deformation portion 30 is inserted from the inside into a hole 11 that penetrates the container body 10 and communicates with the storage space 1A. The press-deformation portion 30 inserted into the hole 11 closes the hole 11. The press-deformation portion 30 is made of an elastic material. The press-deformation portion 30 elastically deforms when pressed from the outside with the penetration direction of the hole 11 being the pressing direction 30A.

[0059] If the pressure-deformation portion 30 is provided on the lower main body 12, there is a possibility that the pressure-deformation portion 30 may hinder the foreign body inspection when performing the foreign body inspection after filling the storage space 1A with liquid. However, by providing the pressure-deformation portion 30 on the inner plug member 14, the foreign body inspection can be performed smoothly. Furthermore, since the cap 40 fits into the lower body 12, if the pressure-deforming portion 30 is provided on the lower body 12, there is a possibility that the shape of the lower body 12 will be restricted. However, by providing the pressure-deforming portion 30 on the middle plug member 14, it is possible to prevent restrictions on the shape of the lower body 12.

[0060] The pressure-deformable portion 30 elastically deforms between a first position A1, which protrudes outside the container body 10 when not pressed and forms a space 35 inside that communicates with the storage space 1A, and a second position A2, which is located closer to the storage space 1A than the first position A1 when pressed, so that the liquid (ophthalmic composition) is ejected from the ejection port due to the change in volume between the first position A1 and the second position A2.

[0061] FIG. 4 is an enlarged partial cross-sectional view of the pressure-deformed portion 30 in the non-pressed state in FIG. The pressure-deformable portion 30 has a first cylindrical portion 31, a first flange portion 32, a first closing portion 33, and a ring portion .

[0062] The pressure-deformed portion 30 when not pressed will be described below. The first cylindrical portion 31 has a cylindrical shape that passes through the hole 11. The first cylindrical portion 31 fits into the hole 11. Both ends of the first cylindrical portion 31 protrude from the curved wall 16 on both the outer and inner sides. The first flange portion 32 is annular and extends radially outward from the end of the first cylindrical portion 31 on the housing space 1A side. The first flange portion 32 engages with the inner surface of the container body 10 (curved wall 16) from the inside.

[0063] The first closing portion 33 closes the outer end of the storage space 1A in the first cylindrical portion 31. The first closing portion 33 is the portion that comes into contact when the press-deformation portion 30 is pressed from the outside in the pressing direction 30A. The ring portion 34 is provided around the entire outer peripheral surface of the first cylindrical portion 31 on the outside of the container body 10. The ring portion 34 engages with the outer surface of the container body 10 from the outside.

[0064] When not pressed, the pressure-deformable portion 30 projects outward from the container body 10 and assumes a first position A1 where it forms a space 35 therein that communicates with the storage space 1A. When pressed, the pressure-deformation portion 30 assumes a second position A2 indicated by a two-dot chain line, where the portion outside the ring portion 34 is recessed inside the hole 11. The second position A2 is closer to the accommodation space 1A than the first position A1.

[0065] The total volume of the storage space 1A when the pressure-deformation portion 30 is in the second position A2 is smaller than the total volume of the storage space 1A including the space 35 when the pressure-deformation portion 30 is in the first position A1, because the part of the pressure-deformation portion 30 outside the ring portion 34 is submerged inside the hole portion 11.

[0066] Therefore, the volume of air in the storage space 1A when the pressure-deformation portion 30 is in the second position A2, minus the amount of liquid contained in the storage space 1A, is smaller than the volume of air in the storage space 1A when the pressure-deformation portion 30 is in the first position A1.

[0067] That is, when the pressure-sensitive deformation portion 30 elastically deforms from the first position A1 to the second position A2 with the discharge port 20 facing downward and the liquid in the storage space 1A in contact with the discharge flow path 21, the air in the storage space 1A is not discharged from the discharge port 20 and remains at a constant amount. On the other hand, when the pressure-sensitive deformation portion 30 elastically deforms from the first position A1 to the second position A2, the volume of the storage space 1A decreases, causing a volume change in the air in the storage space 1A that decreases the volume. As the volume of the air in the storage space 1A decreases, the air pressure in the storage space 1A increases. As a result, the ejection force on the liquid increases, causing the liquid to be ejected from the ejection port 20.

[0068] Therefore, by setting the volume change of the storage space 1A when the pressure-deformation portion 30 elastically deforms from the first position A1 to the second position A2 to a volume change equivalent to one droplet of liquid, one droplet of liquid can be dropped at a constant volume from the discharge port 20 when the pressure-deformation portion 30 is pressed from the first position A1 to the second position A2.

[0069] Furthermore, since the pressure deformation portion 30 is provided on the curved wall 16 which is curved in an arc shape, when viewed from the front, the outer surface of the curved wall 16 curves in a direction away from the tangent line at the intersection with the central axis of the hole portion 11 as it moves away from the hole portion 11. Therefore, when the pressure-deformable portion 30 is pressed with a finger, the surface of the finger is prevented from coming into contact with the outer peripheral surface of the curved wall 16.

[0070] Therefore, when the pressure-deformation portion 30 is pressed with a finger, the finger surface can be pressed firmly to the second position A2 where the portion outside the ring portion 34 is sunk inside the hole portion 11, while preventing contact between the surface of the finger and the outer surface of the curved wall 16. From the viewpoint of ease of pressing, it is preferable that the pressure-deformable portion 30 has a cylindrical shape rather than a rectangular tubular shape such as a square pillar.

[0071] In addition, when the pressure-deformation portion 30 elastically deforms from the first position A1 to the second position A2, liquid is ejected from the outlet 20, but if the pressure on the pressure-deformation portion 30 is stopped halfway through the elastic deformation reaching the second position A2, it is preferable to set the size of the space 35 so that liquid is not ejected from the outlet 20.

[0072] The inner diameter of the pressure-deformable portion 30 is preferably 1 to 20 mm, more preferably 1.5 to 10 mm. When the inner diameter of the pressure-deformable portion 30 is within the above range, the ophthalmic composition to be discharged can be more accurately determined and can be restored to its original shape more quickly when the pressing force is released. When the cross-sectional shape of the internal space 35 of the pressure-deformable portion 30 is polygonal, the inner diameter of the pressure-deformable portion 30 is the diameter of a circumscribed circle of the cross-sectional shape of the internal space 35.

[0073] The displacement of the pressure-deformable portion 30 (the distance between the first position A1 and the second position A2) is preferably 2 to 10 mm, more preferably 2 to 5 mm. When the displacement of the pressure-deformable portion 30 is within the above range, the volume of the ophthalmic composition to be discharged can be more accurately determined, and the pressure-deformable portion can be restored more quickly when the pressure is released.

[0074] From the viewpoint of dripping an appropriate amount of liquid by the elastic deformation of the pressure-deformation portion 30, it is preferable that the material of the pressure-deformation portion 30 is different from the material of the lower main body 12 and the middle plug member 14, and is a material having elasticity with less hardness than the lower main body 12 and the middle plug member 14. In other words, from the viewpoint of controlling the amount of liquid dripped, it is preferable that only the pressure-deformation portion 30 is deformable, and that the lower body 12 and the inner plug member 14 are formed of a material with high hardness so that they are less likely to deform even when pressed and liquid is not ejected.

[0075] For example, in the case of the lower body 12 and the inside plug member 14 made of polyethylene terephthalate resin (PET), the thickness is preferably 0.8 mm or more. In terms of specific strength, the relationship between the squeeze pressure and the deformation amount of the flattened portion (thickness direction) of the lower body 12 and the center plug member 14 is such that the deformation amount is preferably 2.0 mm or less at a squeeze pressure of 0.5 N or more and 12 N or less, and more preferably 0.3 mm or less at a squeeze pressure of 1.5 N or more and 8 N or less.

[0076] The squeeze pressure and deformation amount are values ​​measured by the following measurement methods. With the discharge outlet 20 facing downward, a push-pull gauge with a rod-shaped jig with a diameter of 25 mm attached to the tip is used to apply pressure to the flat portion (thickness direction) of the container body 10, and the squeeze pressure when one drop is dispensed is measured. In addition, a microgauge is installed on the container body 10, and the amount of deformation of the container body 10 at that time is read.

[0077] The material for the pressure-deformation portion 30 is a material that is less hard than the lower body 12 and the inner plug member 14, such as low-density polyethylene resin (LDPE), silicone rubber, urethane rubber, styrene-based elastomer, olefin-based elastomer, polyurethane-based elastomer, or polyester-based elastomer, and from the standpoint of moldability and ease of pressing, low-density polyethylene, silicone rubber, or styrene-based elastomer is preferred.

[0078] The amount of liquid dropped from the discharge port 20 per drop is preferably 5 to 50 mg, and more preferably 20 to 40 mg. When the liquid content is eye drops (ophthalmic composition), the efficacy of the content can be further enhanced by making the volume of each drop of liquid equal to or greater than the above-mentioned lower limit. By making the volume of each drop of liquid equal to or less than the above-mentioned upper limit, the liquid that is dropped onto the eyeball is less likely to overflow. One drop of liquid is 5mm 3 Above 50mm 3 By setting the amount as below, it is possible to drip an amount of liquid that can fully exert the efficacy of the contents without wasting the contents. For the same reason as above, the amount of liquid dropped from the discharge port 20 is set to 5 mm 3 Above 50mm 3 It is preferable that the volume is not more than 5 μL and not more than 50 μL.

[0079] When the liquid content is an eye drop (ophthalmic composition), the capacity of the container body 10 is preferably 5 mL or more and 20 mL or less. Considering the action of holding the container body 10 in one hand, fixing it in a position above the face, and pressing the pressure-deformable portion 30 with a finger to eject and drip the liquid, the volume of the container body 10 is preferably in the above range. By keeping the volume of the eye drops (ophthalmic composition) at 20 mL or less, usability is further improved. As shown in Figure 2, if the first intersection angle, which is the not smaller of the intersection angles between the pressing direction 30A of the pressure deformation portion 30 and the ejection direction 20A of the liquid from the ejection port 20, is θ1, the first intersection angle θ1 is preferably greater than or equal to 90° and less than 180°, and more preferably greater than or equal to 90° and less than or equal to 115°, for example, 102°.

[0080] For example, when the container body 10 is held in one hand with the thumb on the front side of the container body 10 and the middle finger, ring finger, and little finger on the back side, and the index finger is pressed in the pressing direction 30A with the container body 10 fixed in a position above the face, by setting the first intersection angle θ1 to be 90° or more and less than 180°, the distance between the discharge outlet 20 and the eye (eyeball) can be maintained at an appropriate value, and the user can be induced to adopt a posture with their arms tucked in when the index finger is pressed in the pressing direction 30A with the container body 10 fixed in a position above the face. By administering eye drops with your arms folded, it becomes easier to aim at the target (eyeball) and the pressing action becomes more stable, improving usability.

[0081] Furthermore, by making the pressure-deformation portion 30 and the discharge port 20 positioned at the same thickness, when the pressure-deformation portion 30 is pressed in the pressing direction 30A with the index finger while fixed in a position above the face, it becomes easier to guide the user into a posture with the arms tucked in to administer eye drops, thereby improving usability when administering eye drops, such as preventing hand shake.

[0082] As shown in FIG. 2, when the liquid dripping container 1 is in an upright position, the second intersection angle θ2 is the smaller of the intersection angles of the pressing direction 30A with respect to the up-down direction. The second intersection angle θ2 is preferably greater than or equal to 0° and less than 90°, more preferably greater than or equal to 30° and less than or equal to 60°, for example, 45°. By setting the second intersection angle θ2 to be greater than or equal to 0° and less than 90°, when the container body 10 is held in one hand with the thumb placed on the front side of the container body 10 and the middle finger, ring finger, and little finger placed on the back side, and the container body 10 is fixed in a position above the face, and the index finger is pressed against the pressure-deformation portion 30 in the pressing direction 30A, the index finger can be placed on the pressure-deformation portion 30 without applying undue force to the joints of the finger, and the container body 10 can be held so as to be supported by the palm of the hand, allowing for pressing in a more stable posture.

[0083] A method for using the liquid dropping container of this embodiment will be described. The discharge port 20 is held downward and directed toward the object to be discharged. While holding the container body 10 with one hand, the pressure-deforming portion 30 is pressed fully in the pressing direction 30A with the index finger or the like. When the pressure-deforming portion 30 is fully pressed, a constant volume of the ophthalmic composition equivalent to the volume pressed in is discharged. At this time, the pressure-deformable portion 30 is quickly deformed, and when the ophthalmic composition is discharged, the ophthalmic composition is unlikely to remain on the outer surface of the discharge port 20 . The pressing force on the pressure-deformable portion 30 required to deform the pressure-deformable portion 30 from the first position A1 to the second position A2 and discharge the ophthalmic composition from the discharge port at a constant volume is preferably 6 N or less, more preferably 5.5 N or less. If the pressing force is equal to or less than the above upper limit, the pressure-deformable portion 30 is quickly deformed when pressed by standard operation and quickly returns to the first position A1 from the second position A2, making it difficult for the ophthalmic composition to remain on the outer surface of the discharge port 20. The lower limit of the pressing force is preferably 0.1 N or more, more preferably 0.5 N or more. If the pressing force is equal to or greater than the above lower limit, discharge of the ophthalmic composition due to incorrect operation can be more effectively prevented.

[0084] In the liquid dripping container 1 of this embodiment, one drop can be dripped at a constant volume by fully pressing the pressure-deforming portion 30, making it easier for the user to recognize the timing at which the liquid is being ejected and preventing unnecessary amounts of liquid from being dripped. In addition, the liquid dropping container 1 of this embodiment has a pressure-deformable portion that can dispense a constant volume, so that residual liquid around the discharge port 20 can be prevented.

[0085] <Second embodiment of liquid dripping container> Next, a second embodiment of the liquid dripping container 1 will be described with reference to FIG. In this figure, the same elements as those in the first embodiment shown in FIGS. 1 to 4 are given the same reference numerals, and the description thereof will be omitted. In the second embodiment, the configuration of the pressure-deformation portion 30 is different from that in the first embodiment.

[0086] 5 is an enlarged partial cross-sectional view of the pressure-deformation portion 30 in the non-pressed state according to the second embodiment. As shown in FIG. 5, the pressure-deformation portion 30 has a second tubular portion 41, a second flange portion 42, and a second closing portion 43.

[0087] The second cylindrical portion 41 has a cylindrical shape that extends outward from the outer surface of the container body 10 at the periphery of the hole 11 when the press-deformation portion 30 is not pressed. The inner peripheral surface of the second cylindrical portion 41 is flush with the inner peripheral surface of the hole 11. The second flange portion 42 has an annular shape that extends radially outward from the end of the second cylindrical portion 41 on the housing space 1A side. The second flange portion 42 is flush with the outer surface of the container body 10. The second flange portion 42 engages with the outer surface of the container body 10. The second closing portion 43 closes the outer end of the container body 10 in the second cylindrical portion 41. The second closing portion 43 is a portion that comes into contact when the press-deformable portion 30 is pressed from the outside in the pressing direction 30A.

[0088] The pressure-deformable portion 30 and the inside plug member 14 (container body 10) are an integrally molded body. The second flange portion 42 is fixed to the inside plug member 14 by welding. The other configurations are the same as those of the first embodiment.

[0089] In the liquid dripping container 1 of this embodiment, in addition to obtaining the same functions and effects as those of the first embodiment, since the pressure-deformation portion 30 and the inner plug member 14 are integrally molded into a molded body, the process of incorporating the pressure-deformation portion 30 into the inner plug member 14 is not required, thereby improving manufacturing efficiency.

[0090] <Third embodiment of liquid dripping container> Next, a third embodiment of the liquid dripping container 1 will be described with reference to FIGS. In these figures, the same elements as those in the first embodiment shown in FIGS. 1 to 4 are denoted by the same reference numerals, and the description thereof will be omitted.

[0091] Fig. 6 is a perspective view showing a liquid dripping container 1 according to a third embodiment. Fig. 7 is a front view showing the liquid dripping container 1 in an upright state according to the third embodiment. Fig. 8 is a partial cross-sectional view showing an enlarged view of the pressure-deformable portion 30 in an unpressed state in Fig. 7.

[0092] 6 and 7, the liquid dripping container 1 has a container body 10 and a protrusion 50. The container body 10 has an elliptical outer contour extending in the width direction (left-right direction in FIG. 7) and extends in the up-down direction. The container body 10 is formed so that the maximum dimension in the width direction is larger than the maximum dimension in the thickness direction (direction perpendicular to the plane of the paper in FIG. 7), which is perpendicular to the up-down direction and width direction.

[0093] Since the maximum width dimension of the container body 10 is formed to be larger than the maximum thickness dimension, for example, when the container body 10 is held with the thumb in contact with the front side of the container body 10 and the middle finger, ring finger, and little finger in contact with the back side, the index finger can easily press the pressure deformation portion 30 described later from the side opposite the discharge outlet 20.

[0094] The container body 10 has a mouth 10A that opens upward. The mouth 10A is cylindrical and extends in the vertical direction. A protrusion 50 is inserted into the mouth 10A from above and fixed thereto.

[0095] The protrusion 50 is cylindrical and protrudes upward from the container body 10. The protrusion 50 has a discharge outlet 20 and a pressure-deformation portion 30. The protrusion 50 has an inclined portion 51 that slopes downward as it approaches the right side, which is the other side in the width direction. The discharge outlet 20 is provided on the left side, which is one side in the width direction of the protrusion 50. The pressure-deformation portion 30 is provided on the right side in the width direction. The pressure-deformation portion 30 protrudes from the inclined portion 51, with the pressing direction being perpendicular to the inclined portion 51. The pressure-deformation portion 30 is cylindrical and has a top portion that protrudes upward from the inclined portion 51.

[0096] The protrusion 50 and the pressure-deforming portion 30 may be made of the same material, and may be integrally molded by, for example, injection molding. Examples of materials for the protrusion 50 and the pressure-deformation portion 30 include polyethylene terephthalate resin (PET), polybutylene terephthalate resin (PBT), high-density polyethylene resin (HDPE), low-density polyethylene resin (LDPE), and polypropylene resin (PP), with high-density polyethylene resin (HDPE), low-density polyethylene resin (LDPE), and polypropylene resin (PP) being more preferred.

[0097] The pressure-deformable portion 30 may be formed of a material having a lower hardness than the protrusion 50. Examples of materials having a lower hardness than the protrusion 50 include low-density polyethylene resin (LDPE), silicone rubber, urethane rubber, styrene-based elastomer, olefin-based elastomer, polyurethane-based elastomer, and polyester-based elastomer, and from the viewpoints of moldability and ease of pressing, low-density polyethylene, silicone rubber, and styrene-based elastomer are preferred.

[0098] If the material of the pressure-deformation portion 30 is less hard than the protrusion 50, when the pressure-deformation portion 30 is pressed toward the inclined portion 51, the pressure-deformation portion 30 deforms to follow the inclined portion 51, which has a greater hardness, and therefore the pressing direction 30A of the pressure-deformation portion 30 is perpendicular to the inclined portion 51. As shown in Figures 7 and 8, for example, by holding the container body 10 with the thumb in contact with the front side of the container body 10 and the middle finger, ring finger, and little finger in contact with the back side, and pressing the right end of the upper end of the pressure-deformation portion 30 with the index finger from the side opposite the discharge outlet 20 toward the inclined portion 51 in the pressing direction 30A, one drop of liquid can be dispensed from the discharge outlet 20.

[0099] Of the intersection angles between the pressing direction 30A of the pressure deformation portion 30 and the ejection direction 20A of the liquid from the ejection port 20, the first intersection angle θ1 on the not-smaller side is preferably greater than or equal to 90° and less than 180°, and more preferably greater than or equal to 90° and less than or equal to 125°, for example, 115°.

[0100] Of the intersection angles of the pressing direction 30A with the up-down direction when the liquid dripping container 1 is in an upright state, the smaller second intersection angle θ2 is preferably greater than or equal to 0° and less than 90°, more preferably greater than or equal to 15° and less than or equal to 60°, for example, 30°.

[0101] In the liquid dripping container 1 of this embodiment, in addition to obtaining the same functions and effects as those of the first embodiment, the protrusion 50 and the pressure-deforming portion 30 are integrally molded from one or more materials, thereby reducing manufacturing costs.

[0102] <Fourth embodiment of liquid dripping container> Next, a fourth embodiment of the liquid dripping container 1 will be described with reference to FIGS. In these figures, the same elements as those in the third embodiment shown in FIGS. 6 to 8 are denoted by the same reference numerals, and the description thereof will be omitted.

[0103] Fig. 9 is a front view showing the liquid dripping container 1 in an upright state according to the fourth embodiment. Fig. 10 is a plan view of the liquid dripping container 1 according to the fourth embodiment. Fig. 11 is an enlarged partial cross-sectional view of the protrusion 50 in Fig. 9.

[0104] As shown in Fig. 9, the liquid dripping container 1 has a container body 10 and a protrusion 50. As shown in Fig. 10, the container body 10 has an elliptical outer contour extending in the width direction and extends in the up-down direction. The container body 10 is formed so that the maximum dimension in the width direction is larger than the maximum dimension in the thickness direction, which is perpendicular to the up-down direction and the width direction.

[0105] Since the maximum width dimension of the container body 10 is formed to be larger than the maximum thickness dimension, for example, when the container body 10 is held with the thumb in contact with the front side of the container body 10 and the middle finger, ring finger, and little finger in contact with the back side, the index finger can easily press the pressure deformation portion 30 described later from the side opposite the discharge outlet 20.

[0106] The protrusion 50 protrudes upward from the container body 10. The protrusion 50 is formed in a truncated cone shape with a diameter that decreases toward the top. The protrusion 50 has a discharge outlet 20 and a pressure-deformation portion 30. The protrusion 50 has an inclined portion 51 that slopes downward toward the right side, which is the other side in the width direction. The protrusion 50 has a second inclined portion 52 that slopes downward toward the left side, which is one side in the width direction.

[0107] The discharge port 20 is provided on the left side in the width direction of the protrusion 50. The discharge port 20 is provided in the second inclined portion 52. The pressure-deformable portion 30 is provided on the right side in the width direction. The pressure-deformable portion 30 protrudes from the inclined portion 51, with the pressing direction being perpendicular to the inclined portion 51. The pressure-deformable portion 30 has a spherical portion 30B protruding from the inclined portion 51. By having the spherical portion 30B in the pressure-deformable portion 30, the feel when pressing the pressure-deformable portion 30 with a finger can be made softer.

[0108] The protrusion 50 and the pressure-deforming portion 30 may be made of the same material, and may be integrally molded by, for example, injection molding. Examples of materials for the protrusion 50 and the pressure-deformation portion 30 include polyethylene terephthalate resin (PET), polybutylene terephthalate resin (PBT), high-density polyethylene resin (HDPE), low-density polyethylene resin (LDPE), and polypropylene resin (PP), with high-density polyethylene resin (HDPE), low-density polyethylene resin (LDPE), and polypropylene resin (PP) being more preferred.

[0109] The pressure-deformable portion 30 may be formed of a material having a lower hardness than the protrusion 50. Examples of materials having a lower hardness than the protrusion 50 include low-density polyethylene resin (LDPE), silicone rubber, urethane rubber, styrene-based elastomer, olefin-based elastomer, polyurethane-based elastomer, and polyester-based elastomer, and from the viewpoints of moldability and ease of pressing, low-density polyethylene, silicone rubber, and styrene-based elastomer are preferred.

[0110] Of the intersection angles between the pressing direction 30A of the pressure deformation portion 30 and the liquid ejection direction 20A from the ejection port 20, the first intersection angle θ1 on the not smaller side is preferably greater than 90° and less than 180°, more preferably greater than 90° and less than 115°, for example, 90°.

[0111] Of the intersection angles of the pressing direction 30A with the up-down direction when the liquid dripping container 1 is in an upright state, the second intersection angle θ2 on the smaller side is preferably greater than or equal to 0° and less than 90°, more preferably greater than or equal to 30° and less than or equal to 60°, for example, 45°.

[0112] In the liquid dripping container 1 described above, for example, the container body 10 can be held with the thumb touching the front side of the container body 10 and the middle finger, ring finger, and little finger touching the back side, and one drop of liquid can be dripped from the discharge outlet 20 by pressing the spherical portion 30B of the pressure-deforming portion 30 with the index finger from the side opposite the discharge outlet 20 toward the inclined portion 51 along the pressing direction 30A.

[0113] In the liquid dripping container 1 of this embodiment, in addition to obtaining the same functions and effects as those of the first embodiment, it is possible to reduce manufacturing costs by integrally molding the protrusion 50 and the press-deformation portion 30 from one or more materials. Furthermore, in the liquid dripping container 1 of this embodiment, the press-deformation portion 30 has a spherical portion 30B, which makes it possible to soften the feel when pressing the press-deformation portion 30 with a finger.

[0114] <Other embodiments> While the preferred embodiments of the present invention have been described above with reference to the accompanying drawings, it goes without saying that the present invention is not limited to these examples. The shapes and combinations of the components shown in the above examples are merely examples, and various modifications can be made based on design requirements, etc., without departing from the spirit of the present invention.

[0115] For example, in the first and second embodiments, the container body 10 is shaped like a rectangular tube, but the container body 10 is not limited to this configuration. As shown in the modified example of Fig. 12, the container body 10 may have a configuration in which the lower body 12 has a disk-shaped bottom 13, is cylindrical in shape with a circular cross section, and extends in the vertical direction, and the inner plug member 14 has an inclined wall 15 and an inclined wall 16A. The inclined wall 16A is located to the right of the inclined wall 15 and is linearly inclined downward as it goes to the right. The discharge port 20 is provided in the inclined wall 15, and the pressure-deforming portion 30 is provided in the inclined wall 16A.

[0116] In the container body 10 of the liquid dripping container 1 in this modified example, in addition to being able to obtain the same functions and effects as the above embodiment, the lower body 12 is cylindrical, which makes it feel gentle to hold. The shape of the container body 10 can be selected from various shapes such as a cylindrical shape, an oval shape, and the like, in addition to the above.

[0117] In the third embodiment, the protrusion 50 is cylindrical, but the present invention is not limited to this. For example, the protrusion 50 may be frustum-shaped as in the fourth embodiment, and the discharge port 20 may be provided on a second inclined portion that is inclined downward as it approaches one side in the width direction.

[0118] In the liquid dropping container of the above-described embodiment, the pressure-deformable portion protrudes from the container body, but the present invention is only required to be able to dispense the ophthalmic composition at a constant volume. For example, the pressure-deformable portion of the liquid dripping container may be a part of the wall (e.g., a corner, a flat portion, etc.) that constitutes the container body and that is easily displaced by a pressure and quickly restored when the pressure is released. More specifically, the pressure-deformable portion may be formed by making only a specific region of the wall thin or made of a material that is easily elastically deformed.

[0119] As described above, the liquid dripping container of the present invention may be a so-called one-push type container that can drip a constant volume of liquid from the outlet 20 by pressing the pressure-deformation portion 30 from the first position A1 to the second position A2.

[0120] <Sterilization> Since the ophthalmic composition is a sterile preparation, it is preferable that the container body be sterilized. Specifically, the sterilization method can be any of ethylene oxide gas sterilization, electron beam sterilization, and gamma ray sterilization. Electron beam sterilization is more preferable because there is no concern about residual gas and the sterilization can be completed in a short time.

[0121] <Enclosure> The ophthalmic product may have a housing for packaging the container, such as polyethylene, polyethylene terephthalate, polypropylene, polybutylene, polycarbonate, polyester, nylon, cellophane, polyvinyl chloride film, aluminum foil, aluminum-deposited polyvinyl alcohol or polyamide film, polyvinylidene chloride-coated film or laminate film, or composite or multilayer film thereof.

[0122] An inert gas such as nitrogen may be sealed in the space formed between the container and the enclosure, and the ophthalmic composition may be filled into the container and then sealed in the enclosure together with an oxygen scavenger. Examples of the means include (1) injecting an inert gas into the enclosure, (2) packaging an oxygen absorber in the enclosure, (3) a container having oxygen absorbing capacity, or (4) an enclosure having oxygen absorbing capacity. By using such means, the problems of the present invention can be solved, the decrease in transmittance of the ophthalmic composition can be further suppressed, and the appearance stability can be improved. (1) Injection of inert gas into the enclosure Examples of inert gases include nitrogen, helium, neon, and argon. Of these, nitrogen gas is preferred. The concentration of the inert gas is preferably 50% by volume or more, more preferably 80% by volume or more, and even more preferably 90% by volume or more, in the volume of the space formed between the enclosure and the plastic container. There is no particular upper limit, but it is 100% by volume or less. To achieve such a concentration, the space formed between the enclosure and the plastic container may be replaced with the inert gas. (2) Packing oxygen absorbers inside the enclosure Specifically, it is possible to use Ageless (registered trademark) (FX, SP, SS, SPE, ZP, Z-PT, Z-PKC, GLS, GL-M, Z-20PKya) manufactured by Mitsubishi Gas Chemical Company, Inc., Pharmakeep, Vitalon manufactured by Tokiwa Sangyo Co., Ltd., Sunsoles manufactured by Hiroyo Co., Ltd., Wonderkeep manufactured by Powdertech Co., Ltd., Sunsocut manufactured by Iris Fine Products Co., Ltd., etc. (3) Container having oxygen absorption ability Specifically, for example, it is possible to use Oxyblock manufactured by Toyo Seikan Co., Ltd., etc. (4) Enclosure having oxygen absorption ability Specifically, it is possible to use Oxycatch (registered trademark) ICA manufactured by Kyodo Printing Co., Ltd., Cryovac (registered trademark) OS film manufactured by Shield Air Japan Co., Ltd., Highster O2 manufactured by Star Plastic Industry Co., Ltd., Ageless Ormax manufactured by Mitsubishi Gas Chemical Company, Inc., Oxideck manufactured by Toyo Seikan Co., Ltd., etc. The above means can be combined as appropriate, (2) and (4) are preferable, and the combination of (1) and (2) and the combination of (1) and (4) are more preferable.

Example

[0123] Hereinafter, the present invention will be described in detail with reference to examples, but the present invention is not limited to the following description. In addition, the blending amounts of the components used in each example are values in terms of pure components unless otherwise specified.

[0124] (Measurement method) <pH measurement> For the measurement of the pH of the ophthalmic composition, a pH meter (manufactured by Toa DKK Corporation, trade name "HM-25R") was used. The ophthalmic composition to be measured was temperature-adjusted to 25°C and the pH was measured. For the measurement of viscosity, a cone and plate type viscometer was used as a B-type rotational viscometer, and the measurement was carried out under the conditions of a measurement temperature of 25 degrees, a cone spindle CPA-42Z, a rotation speed of 50 RPM, and measurement after 1 minute.

[0125] (Evaluation method) <Residual liquid> The ophthalmic composition was placed in each container to prepare an ophthalmic product (eye drops). One drop (35 mg in both Examples and Comparative Examples) was dropped into the eye drop nozzle by tilting it downward at a 45° angle. The remaining liquid around the nozzle was then absorbed with filter paper and weighed to evaluate the amount of remaining liquid. Each container was measured five times, and the average value was calculated. After dropping one drop in the same manner as above, the container was left standing at room temperature with the outlet facing upward, and after 6 hours the appearance of the outlet was observed and the presence or absence of whitening was evaluated according to the following evaluation criteria. <Evaluation Criteria> ×: Whitening occurs. ○: No bleaching.

[0126] <Measurement of pressing force> For Examples 2, 6, 12, 14, and 16 and corresponding comparative examples, the pressing force required to eject one drop of the ophthalmic composition from the ejection port was measured. After filling the target ophthalmic product with the ophthalmic composition, the ejection port was oriented directly downward in an unused state and fixed with a jig to maintain this state. Next, a pressing jig attached to the tip of a digital push-pull gauge was used to apply pressure to the side or deformed portion of the container, and the squeeze force (N) required to eject one drop was measured. The measurement was repeated 10 times (for 10 drops), and the average was calculated.

[0127] (Raw materials used) The raw materials used are listed below. Unless otherwise specified, the amount of each ingredient in the table is the pure equivalent. The terms "JP," "Extra-Pharmacopoeia Standards," and "Pharmaceutical Additive Standards" below refer to raw materials that comply with the 18th Revised Japanese Pharmacopoeia Standards, the Japanese Pharmacopoeia Extra-Pharmacopoeia Standards, and the Pharmaceutical Additive Standards (2018), respectively.

[0128] <Component (A)> Potassium L-aspartate: (trade name: Potassium L-aspartate, Alps Pharmaceutical Co., Ltd., extra-official regulations), equivalent to component (a1). Taurine (aminoethylsulfonic acid): (trade name: Taurine, Three F Co., Ltd., JP), equivalent to component (a1). Chondroitin sulfate sodium: (Product name: Non-regulated sodium chondroitin sulfate, Maruha Nichiro Corporation, non-regulated), equivalent to component (a2). Sodium hyaluronate: (trade name: Hyaluronsan HA-AML (JP), Kewpie Corporation, JP), equivalent to component (a2). Potassium chloride: (Product name: Japanese Pharmacopoeia Potassium Chloride, Ako Kasei Co., Ltd., JP), equivalent to component (a4). Sodium chloride: (Product name: Japanese Pharmacopoeia Sodium Chloride SG, manufactured by Tomita Pharmaceutical Co., Ltd., Japan Pharmacopoeia), equivalent to component (a4). Povidone: (trade name: Povidone K90 (Kollidon 90F), BASF Japan Ltd., Japanese Pharmacopoeia), equivalent to component (a3). Hypromellose (hydroxypropyl methylcellulose): (trade name: Metrose 60SH-4000, Shin-Etsu Chemical Co., Ltd., Japanese Pharmacopoeia), corresponds to component (a3).

[0129] <Optional ingredients> Boric acid: (trade name: Boric Acid, Kanto Chemical Co., Ltd., Japanese Pharmacopoeia). Dilute hydrochloric acid: (trade name: Dilute Hydrochloric Acid, Kosakai Pharmaceutical Co., Ltd., Japanese Pharmacopoeia). Sodium hydroxide: (trade name: Sodium Hydroxide, Kosakai Pharmaceutical Co., Ltd., Japan Pharmacopoeia). ·Water: Purified water.

[0130] (Examples 1 to 16) Each ophthalmic composition was prepared by a conventional method according to the formulation shown in Tables 1 to 4. The resulting ophthalmic composition was filled into a container (one-push type container) having the configuration shown in Figures 6 to 8 to obtain an ophthalmic product. The container body was made of polyethylene terephthalate resin (PET), the protrusions were made of polypropylene resin (PP), the pressure-deformed portion was made of styrene-based elastomer, and the discharge port was made of polypropylene resin (PP). The capacity of the container body was 20 mL, and the amount of ophthalmic composition filled was 15 mL. The opening diameter of the discharge port was 2 mm, and the displacement of the pressure-deformed portion was 3 mm. This container is labeled "A" in the table. In the table, the "appropriate amount" of pH adjuster content means the amount required to adjust the pH of each ophthalmic composition at 25°C to the value in the table. The "balance" of water content is the amount required to make the total amount of the ophthalmic composition 100%. The resulting ophthalmic product was evaluated for residual liquid, and the results are shown in the table.

[0131] (Comparative Examples 1 to 16) An ophthalmic product was obtained in the same manner as in Examples 1 to 16, except that the liquid dripping container was changed to the liquid dripping container 100 shown in FIG. The resulting ophthalmic product was evaluated for residual liquid, and the results are shown in the table.

[0132] The liquid dripping container 100 will now be described. 13 has a container body 110 and a cap (not shown). The container body 110 has a body 112, a spout 114 protruding from the upper end of the body 112, and a discharge port 120 located at the tip of the spout 114. As shown in Figure 13(a), the shape of the body 112 is an octagon when viewed from the front. As shown in Figure 13(b), the body 112 has a flat shape with one long side and the other short side when viewed from above. The body 112 and the mouth 114 are integrally molded from PET, and the discharge port 120 is molded from PE. The volume of the container body was 20 mL, the amount of the ophthalmic composition filled was 15 mL, and the opening diameter of the discharge port was 2 mm. The ophthalmic products of each comparative example were used by directing the discharge port toward the pupil and pressing the body 112 to discharge the ophthalmic composition. At this time, the body 112 was pressed in the short direction in a plan view of the container body 110. In the ophthalmic products of the comparative examples, the entire surface of the body 112 was pressed, so the volume could not be stably determined. This container is labeled "B" in the table.

[0133] [Table 1]

[0134] [Table 2]

[0135] [Table 3]

[0136] [Table 4]

[0137] As shown in the results in Tables 1 to 4, in Examples 1 to 16 in which the present invention was applied, the residual liquid was 0 mL and no whitening was observed. The viscosity of the examples and comparative examples was 1.1 to 20 mPa·s.

[0138] Formulation Examples 1 to 27 of ophthalmic compositions are shown in Tables 5 and 6. The unit of content of each component is w / v % unless otherwise specified.

[0139] [Table 5]

[0140] [Table 6]

[0141] [Table 7]

[0142] [Table 8] [Explanation of symbols]

[0143] 1...liquid drip container, 1A...accommodation space, 10...Container body, 11...hole, 12...lower main body, 14...Inner plug member, 20...Discharge port, 20A…Discharge direction, 30...Pressure deformation portion, 30A...Pressing direction, 30B…spherical part, 31...first cylinder part, 32...first flange portion, 33...first occlusion part, 34...Ring section, 35...space, 41...Second cylinder part, 42...second flange portion, 43...second occlusion part, 50...Protruding body, 51...slanted part, 52...second slope part, θ1: First intersection angle θ2...Second intersection angle.< / ph>

Claims

1. An ophthalmic product comprising a liquid ophthalmic composition and a liquid dropper container filled with the ophthalmic composition, the liquid dripping container has a container body having a discharge port and a pressure-deformable portion, and an accommodation space for accommodating liquid therein, and a cap; the liquid dripping container is configured such that the pressure-deformed portion is pressed and deformed to discharge the ophthalmic composition at a constant volume from the discharge port, and then the pressure on the pressure-deformed portion is released to make it non-pressurized, whereby the shape of the pressure-deformed portion is restored; An ophthalmic product, wherein the ophthalmic composition comprises at least one selected from amino acids and salts thereof, mucopolysaccharides and salts thereof, water-soluble polymers, inorganic chlorides, inorganic carbonates, inorganic sulfates, and inorganic phosphates.

2. The pressure-deformation portion is formed of an elastic material, The ophthalmic product of claim 1, wherein the pressure-deformable portion elastically deforms between a first position in which it protrudes outside the container body when not pressed and forms a space inside that communicates with the storage space, and a second position in which it is located closer to the storage space than the first position when pressed, and the ophthalmic composition is ejected from the ejection port due to the change in volume between the first position and the second position.

3. The ophthalmic product according to claim 1 or 2, wherein a pressing force applied to the press-deformed portion when the ophthalmic composition is discharged from the discharge port at a constant volume is 6 N or less.

4. The ophthalmic product according to claim 1 or 2, wherein the fixed volume is 5 to 50 mg.

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