Ophthalmic products

Abstract

To provide an ophthalmic product having good reproducibility of discharge operation and reduced variation in discharge amount per drop.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-deforming portion and having a storage space for storing a liquid therein, and a cap, and the press-deforming portion is formed of an elastic material, the press deformation portion is elastically deformed between a first position at which the press deformation portion protrudes to the outside of the container body and forms a space communicating with the storage space inside the container body when the press deformation portion is not pressed and a second position at which the press deformation portion is positioned closer to the storage space than the first position when the press deformation portion is pressed, the ophthalmic composition is discharged from the discharge port by a volume change between the first position and the second position, and the ophthalmic composition contains (A) a nonionic surfactant and (B) an oily component.SELECTED DRAWING: Figure 1

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] However, the method of Patent Document 1 merely discloses eye drops filled in a container having a specific dispensing nozzle that dispenses a small amount per drop, and the eye drops are dispensed by squeezing the container body, so the reproducibility of the dispensing operation and the improvement of the variation in the amount dispensed per drop are not necessarily sufficient. An object of the present invention is to provide an ophthalmic product that has good reproducibility of the ejection operation and reduced variation in the amount of ejection per droplet. [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 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, An ophthalmic product, wherein the ophthalmic composition comprises (A) a nonionic surfactant and (B) an oily component. [2] The ophthalmic product according to [1], wherein the component (B) is one or more selected from the group consisting of vitamin A, vitamin E, liquid paraffin, sesame oil, and castor oil. [3] The ophthalmic product according to [1] or [2], wherein the component (A) is one or more selected from the group consisting of polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene polyoxypropylene glycol, and polyethylene glycol fatty acid ester. [4] The ophthalmic product according to any one of [1] to [3], further comprising (C) a water-soluble polymer, wherein the water-soluble polymer is one or more selected from the group consisting of polyvinylpyrrolidone, hydroxypropyl cellulose, hydroxypropylmethylcellulose, hydroxyethyl cellulose, methylcellulose, polyvinyl alcohol, hyaluronic acid and its salts, and carboxyvinyl polymers. [5] The ophthalmic product according to any one of [1] to [4], further comprising (D) one or more selected from the group consisting of boric acid, borax, trometamol, and ethylenediamineacetic acid derivatives and salts thereof, and having a pH of 5 to 7.5 at 25°C. [6] The ophthalmic product according to any one of [1] to [5], wherein the amount of one drop of the ophthalmic composition dispensed from the discharge port is 5 mg to 50 mg. [Effects of the Invention]

[0006] According to the present invention, a liquid ophthalmic composition is filled in a liquid dropping container, and an ophthalmic product can be obtained that has good reproducibility of the ejection operation and reduced variation in the amount ejected per drop. [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. 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 HLB of a compound is an index of affinity for water and oil; generally, the closer to 0, the higher the lipophilicity, and the closer to 20, the higher the hydrophilicity. HLB can be calculated using the Atlas method, Griffin method, Davis method, Kawakami method, etc. Alternatively, values ​​published by manufacturers for products can be used as a reference. The concepts of hydrophilicity and lipophilicity in HLB are highly correlated with the concepts of organic value and inorganic value in the organic conceptual diagram, and can be calculated from the IOB value below, which is calculated from the ratio of organic value to inorganic value, using the formula "HLB = IOB × 10." In this specification, HLB is calculated from the IOB value using the above formula.

[0010] The IOB of a compound refers to the inorganic-organic balance of the compound, and is an index that indicates the degree of polarity of the compound. It is a value that represents the ratio of the inorganic to organic properties of the compound, and is expressed as "IOB = inorganic value of the compound / organic value of the compound." Specifically, the organic value is calculated based on the inorganic values ​​of other substituents (inorganic groups) with the "organic value" of one carbon atom in a compound molecule being 20 and the "inorganic value" of one hydroxyl group being 100 (Fujita, "Organic Analysis," Kaniya Shoten (1930); Fujita, "Prediction of Organic Compounds and Organic Conceptual Diagrams (Chemical Area 11-10)" (1957), pp. 719-725; Fujita and Akatsuka, "Systematic Organic Qualitative Analysis (Pure Substances)," Kazama Shoten (1970), p. 487; Koda, "Organic Conceptual Diagrams - Fundamentals and Applications," Sankyo Shuppan (1984), p. 227; Yaguchi, "Emulsion Formula Design Using Organic Conceptual Diagrams," Nippon Emulsion Co., Ltd. (1985), p. 98; R.H.E. Well, J.M. Harrison, L.Berg: Ind. Eng. Chem. 36,871 (1944)).

[0011] ≪Ophthalmic products≫ The ophthalmic product of the present invention comprises a liquid ophthalmic composition and a liquid dropper container filled with the ophthalmic composition. ≪Ophthalmic composition≫ The ophthalmic composition of the present invention is a liquid composition containing component (A) and component (B). In the following description, the unit of content, "%", is "w / v%" unless otherwise specified.

[0012] <Component (A)> Component (A) is a nonionic surfactant. The IOB of component (A) is 0.4 or more, preferably 0.7 or more, and more preferably 0.9 or more, and the HLB of component (A) is 4 or more, preferably 7 or more, and more preferably 9 or more.

[0013] 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.

[0014] Polyoxyethylene castor oil is a compound obtained by addition polymerization of ethylene oxide (EO) with castor oil, and several types are known, each with a different average number of moles of ethylene oxide added. The average number of moles of ethylene oxide added in polyoxyethylene castor oil is not particularly limited, but is exemplified as 3 to 60 moles. Specific examples include polyoxyethylene castor oil 3 (the numerical value indicates the average number of moles of ethylene oxide added, the same applies below), polyoxyethylene castor oil 10, polyoxyethylene castor oil 20, polyoxyethylene castor oil 35, polyoxyethylene castor oil 40, polyoxyethylene castor oil 50, and polyoxyethylene castor oil 60. The number of moles of ethylene oxide added is more preferably 10 to 50, and even more preferably 20 to 40. Polyoxyethylene castor oil and polyoxyethylene hydrogenated castor oil are different components. Among these, polyoxyethylene castor oil 35 is preferred.

[0015] Polyoxyethylene hydrogenated castor oil is a compound obtained by addition polymerization of ethylene oxide with hydrogenated castor oil, and several types with different average molar numbers of ethylene oxide are known. The average molar number of ethylene oxide in polyoxyethylene hydrogenated castor oil is not particularly limited, but examples include 5 to 100 moles. Specific examples include polyoxyethylene hydrogenated castor oil 5 (the number indicates the average molar number of ethylene oxide, the same applies below), polyoxyethylene hydrogenated castor oil 10, polyoxyethylene hydrogenated castor oil 20, polyoxyethylene hydrogenated castor oil 30, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene hydrogenated castor oil 50, polyoxyethylene hydrogenated castor oil 60, polyoxyethylene hydrogenated castor oil 80, and polyoxyethylene hydrogenated castor oil 100. Those that comply with the Pharmaceutical Excipients Standards 2018 are preferred, and polyoxyethylene hydrogenated castor oil 60 is particularly preferred.

[0016] Examples of polyoxyethylene sorbitan fatty acid esters include polyoxyethylene (20) sorbitan monolaurate (polysorbate 20, where the numerical value is the average number of moles of ethylene oxide added, the same applies below), polyoxyethylene (20) sorbitan monopalmitate (polysorbate 40), polyoxyethylene (20) sorbitan monostearate (polysorbate 60), polyoxyethylene (20) sorbitan tristearate (polysorbate 65), and polyoxyethylene (20) sorbitan monooleate (polysorbate 80). Of these, polyoxyethylene (20) sorbitan monooleate (polysorbate 80) is preferred.

[0017] Suitable polyoxyethylene polyoxypropylene glycols are those listed in the Pharmaceutical Excipients Standards 2018. The average degree of polymerization of ethylene oxide is preferably 3 to 200, more preferably 20 to 200, and the average degree of polymerization of propylene oxide is preferably 5 to 100, more preferably 17 to 70. While either a block copolymer or a random copolymer may be used, block copolymers are preferred. Specific examples include polyoxyethylene (200) polyoxypropylene (70) glycol, polyoxyethylene (196) polyoxypropylene (67) glycol, polyoxyethylene (120) polyoxypropylene (40) glycol, polyoxyethylene (160) polyoxypropylene (30) glycol, polyoxyethylene (42) polyoxypropylene (67) glycol, polyoxyethylene (54) polyoxypropylene (39) glycol, and polyoxyethylene (20) polyoxypropylene (20) glycol. Among them, polyoxyethylene (200) polyoxypropylene (70) glycol, polyoxyethylene (196) polyoxypropylene (67) glycol, and polyoxyethylene (120) polyoxypropylene (40) glycol are preferred. Commercially available products include, for example, polyoxyethylene (196) polyoxypropylene (67) glycol under the trade name: Kolliphor P407 [BASF Japan Ltd.] and trade name: Pronon #407P [NOF Corporation]; polyoxyethylene (120) polyoxypropylene (40) glycol under the trade name: Kolliphor P237 [BASF Japan Ltd.], as well as commercially available products listed in the Pharmaceutical Additives Dictionary 2021 (edited by the Japan Pharmaceutical Additives Association, published by Yakuji Nipposha).

[0018] Examples of polyethylene glycol fatty acid esters include polyoxyl 10 stearate (polyethylene glycol 10 monostearate (the numerical value is the average number of moles of ethylene glycol added, the same applies below)), polyoxyl 40 stearate, polyoxyl 45 stearate, and polyoxyl 55 stearate, and among these, polyoxyl 40 stearate is preferred.

[0019] These components (A) can be used alone or in appropriate combination of two or more. Among them, polyoxyethylene hydrogenated castor oil 60, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene (20) sorbitan monooleate (polysorbate 80), polyoxyethylene (196) polyoxypropylene (67) glycol, polyoxyethylene (160) polyoxypropylene (30) glycol, and polyoxyl 40 stearate are preferred, as they further improve the variation in the amount per drop and improve the appearance stability (clarity) of the ophthalmic composition.

[0020] The content of component (A) in the ophthalmic composition is preferably 0.02 to 3%, more preferably 0.05 to 1%. By ensuring that the content is equal to or greater than the lower limit, the variation in the amount per drop is further improved. In addition, the solubilization of component (B) further improves the appearance (transmittance) of the ophthalmic composition. By ensuring that the content is equal to or less than the upper limit, foaming of the ophthalmic composition is suppressed, and the variation in the amount per drop is further improved. In addition, irritation is less likely to occur when applied to the eye.

[0021] <(B) component> Component (B) is an oily component. The IOB of component (B) is less than 0.4, preferably 0.38 or less, and more preferably 0.3 or less. The HLB of component (B) is less than 4, preferably 3 or less, and more preferably 2 or less.

[0022] Examples of oily components include vitamin A, vitamin E, 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 vitamin A, vitamin E, liquid paraffin, sesame oil, and castor oil are preferred.

[0023] Examples of vitamin A include vitamin A itself, vitamin A-containing mixtures such as vitamin A oil, and vitamin A derivatives such as vitamin A fatty acid esters. These can be used alone or in combination of two or more. Specific examples include retinol palmitate, retinol acetate, retinol, retinoic acid, and retinoids. Among these, retinol palmitate is preferred, and a commercially available product is retinol palmitate [1.74 million IU / g], manufactured by DSM. Vitamin E is used as a general term to refer to, for example, tocopherol, tocotrienol, their salts, and derivatives (esters). Specific examples include d-α-tocopherol, dl-α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol, mixed tocopherol, etc. Derivatives thereof include, for example, tocopherol acetate (vitamin E acetate), vitamin E nicotinate, vitamin E succinate, vitamin E linoleate, etc., and these can be used alone or in appropriate combinations of two or more. Among these, tocopherol acetate (d-α-tocopherol acetate, dl-α-tocopherol acetate, etc.) is preferred. Commercially available products include d-α-tocopherol acetate: Riken E acetate α, manufactured by Riken Vitamin Co., Ltd.

[0024] The sesame oil is not particularly limited, and can be obtained from seeds using known extraction or refining methods, or commercially available products. In the present invention, oils that comply with the standards of the 18th edition of the Japanese Pharmacopoeia are preferably used. Examples of commercially available products include sesame oil: Sesame Oil, manufactured by Kaneda Co., Ltd. Castor oil that complies with the standards of the 18th edition of the Japanese Pharmacopoeia can be suitably used, and examples of commercially available products include castor oil: castor oil manufactured by Kosakai Pharmaceutical Co., Ltd.

[0025] Examples of liquid paraffin include light liquid paraffin. For example, KAYDOL manufactured by Shima Trading Co., Ltd. can be used. The viscosity of liquid paraffin correlates with its molecular weight, and when measured by the method 1 (37.8°C) of the 18th edition of the Japanese Pharmacopoeia, the viscosity is 30 to 100 mm. 2 / s is preferable, with a viscosity of 37 to 88 mm 2 / s is more preferable, 74 to 88 mm 2 / s is even more preferable. Paraffin that complies with the standards of the 18th edition of the Japanese Pharmacopoeia can be suitably used. Commercially available liquid paraffin and paraffin products include liquid paraffin: KAYDOL, manufactured by Shima Trading Co., Ltd. The other oily components are not particularly limited, and those obtained by a refining method or commercially available products can be used.

[0026] The component (B) can be used alone or in appropriate combination of two or more types. The content of component (B) in the ophthalmic composition is preferably 0.0001 to 0.5%, more preferably 0.005 to 0.3%, and even more preferably 0.002 to 0.1%. By ensuring that the content is equal to or greater than the lower limit, the variation in the amount per drop is further reduced. In addition, the pharmacological effects of component (B) are more easily achieved. By ensuring that the content is equal to or less than the upper limit, the appearance stability of the ophthalmic composition is further improved. The retinol palmitate is preferably present in the ophthalmic composition at 5,000 to 150,000 units / 100 ml (0.003 to 0.086%), more preferably at 10,000 to 100,000 units / 100 ml (0.006 to 0.057%), and particularly preferably at 10,000 to 70,000 units / 100 ml (0.006 to 0.040%). The content of tocopherol acetate in the ophthalmic composition is preferably 0.005 to 0.5%, more preferably 0.01 to 0.3%, and particularly preferably 0.03 to 0.1%. The amount of sesame oil is preferably 0.0001 to 1%, more preferably 0.001 to 0.5%. The content of castor oil is preferably 0.001 to 0.3%, more preferably 0.01 to 0.15%. The content of liquid paraffin is preferably 0.001 to 0.3%, more preferably 0.01 to 0.15%.

[0027] <(C) component> Component (C) is a water-soluble polymer. Examples of water-soluble polymers include polyvinylpyrrolidone, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, hydroxyethyl cellulose, methyl cellulose, polyvinyl alcohol, hyaluronic acid and its salts, and carboxyvinyl polymers. The component (C) may be used alone or in combination of two or more. Among these, hydroxypropylmethylcellulose and polyvinylpyrrolidone are preferred in terms of the effects of the present invention being more pronounced.

[0028] 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.

[0029] There are no particular limitations on the hydroxypropyl cellulose, and one having a viscosity of 100 to 5,000 mPa·s in a 2% aqueous solution can be suitably used, such as the product name M available from Nippon Soda Co., Ltd.

[0030] 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.

[0031] 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.)).

[0032] 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.)).

[0033] 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).

[0034] The hyaluronic acid and its salts are not particularly limited, and any hyaluronic acid that is commonly used in ophthalmic compositions can be used, including hyaluronic acid and its pharmaceutically and physiologically acceptable salts.Hyaluronic acid obtained by extraction from cockscomb, fermentation using microorganisms, etc. can be used, and there are no particular limitations on the origin or manufacturing method.Hyaluronic acid and its salts can be used alone or in appropriate combination of two or more.Specific examples include hyaluronic acid, sodium hyaluronate, potassium hyaluronate, magnesium hyaluronate, calcium hyaluronate, etc.Among them, 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. The viscosity-average molecular weight is measured by the method for measuring viscosity-average molecular weight described in the "Purified Sodium Hyaluronate" section of the Japanese Pharmacopoeia, 18th Edition, in each monograph. The viscosity-average molecular weight of hyaluronic acid or its salts in the ophthalmic composition is measured by the method for measuring viscosity-average molecular weight described in the "Purified Sodium Hyaluronate Ophthalmic Solution" section of the Japanese Pharmacopoeia, 18th Edition. Note that multiple types of hyaluronic acid or its salts with different viscosity-average molecular weights 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).

[0035] 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.

[0036] When the ophthalmic composition contains component (C), the content of component (C) in the ophthalmic composition is preferably 0.05 to 5%, more preferably 0.1 to 3%, and even more preferably 0.2 to 1%. By ensuring that the content is equal to or greater than the lower limit, moisturizing sensation and tear stabilization effects are more readily achieved. In addition, the combined use of components (A) and (B) further reduces variations in the amount of volume per drop. By ensuring that the content is equal to or less than the upper limit, variations in the amount of volume per drop are further reduced.

[0037] <(D) component> Component (D) is one or more additives selected from boric acid, borax, trometamol, ethylenediamineacetic acid derivatives, and salts thereof. The ophthalmic composition preferably contains one or more types of component (D), and more preferably contains two or more types.

[0038] Examples of ethylenediamineacetic acid derivatives or salts thereof include edetic acid (ethylenediaminetetraacetic acid), ethylenediaminediacetic acid, diethylenetriaminepentaacetic acid, N-(2-hydroxyethyl)ethylenediaminetriacetic acid, and sodium edetate (sodium ethylenediaminetetraacetate, disodium ethylenediaminetetraacetate). Among the (D) components, boric acid and trometamol are preferred because they further reduce variation in the amount dispensed.

[0039] When the ophthalmic composition contains component (D), the content of component (D) in the ophthalmic composition is preferably 0.001 to 5%, more preferably 0.01 to 4%, and even more preferably 0.1 to 3%. By ensuring that the content is equal to or greater than the lower limit, the effects of the present invention are more effectively exhibited and preservative effectiveness is more easily achieved. By ensuring that the content is equal to or less than the upper limit, irritation upon application is less likely to occur, and the usability of the ophthalmic composition is further improved.

[0040] <Water> 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.

[0041] <Other ingredients> The ophthalmic composition may contain appropriate amounts of other components other than the components (A) to (D) and water, provided that the effects of the present invention are not impaired. Other components may be those known in ophthalmic compositions, such as drugs other than those listed as component (B), preservatives, sugars, buffers, pH adjusters, isotonicity agents, stabilizers, cooling agents, polyhydric alcohols, thickeners, etc.

[0042] Drugs other than those listed in component (B) include, for example, 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.), amino acids (potassium L-aspartate, Examples of suitable drugs include hydroxybenzoates, magnesium L-aspartate, potassium and magnesium L-aspartate (equal mixture), aminoethylsulfonic acid (taurine), epsilon aminocaproic acid, etc.), mucopolysaccharides and their salts (chondroitin sulfate sodium, etc.), water-soluble vitamins (flavin adenine dinucleotide sodium, cyanocobalamin, pyridoxine hydrochloride, panthenol, calcium pantothenate, sodium pantothenate, etc., vitamin B; vitamin C; sodium ascorbate, etc.), sulfonamides (sulfamethoxazole, sulfisoxazole, and salts thereof). When these drugs are contained, their content can be selected based on the effective amount of each drug, but is preferably 0.001 to 5%, more preferably 0.001 to 1%, and even more preferably 0.001 to 0.1% of the ophthalmic composition.

[0043] Examples of pH adjusters include inorganic acids and inorganic alkali agents. Specific 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 blended to achieve the desired pH.

[0044] <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. Within this range, the stability of component (B) over time is improved. 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.

[0045] <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.

[0046] <Efficacy> The ophthalmic composition of the present invention can be used as an over-the-counter eye drop effective in treating eye fatigue, blurred vision (when there is a lot of eye mucus, etc.), conjunctival congestion, itchy eyes, blepharitis (sore eyelids), prevention of eye diseases (after swimming, when dust or sweat gets into the eyes, etc.), ophthalmitis caused by ultraviolet rays or other light (snow blindness, etc.), discomfort when wearing hard contact lenses, etc., or as an artificial tear effective in treating discomfort when wearing soft or hard contact lenses, lacrimal supplementation (dry eyes), eye fatigue, blurred vision (when there is a lot of eye mucus, etc.), etc. In particular, when vitamin A is contained as component (B), it repairs corneal scratches and corneal damage caused by mild rubbing, and is effective in treating fatigue (eye fatigue), blurred vision, itching, congestion, etc., which are common causes of these conditions. <Dosage> When the ophthalmic composition of the present invention is used as eye drops, it is preferable to instill 1 to 3 drops of 10 to 100 μL per administration, 1 to 6 times per day, more preferably 1 to 3 drops of 10 to 50 μL per administration, 1 to 6 times per day, and even more preferably 1 to 3 drops of 10 to 30 μL per administration, 1 to 6 times per day.

[0047] <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, first, component (A) and component (B) are mixed to prepare mixture A. Separately, aqueous components other than the pH adjuster are added to a portion of water to prepare aqueous solution B. Next, mixture A and aqueous solution B are mixed to emulsify, and the pH is adjusted with the pH adjuster as necessary. The total volume of the ophthalmic composition is then adjusted with the remaining water to obtain the ophthalmic composition. The mixing temperature for each component is not particularly limited, but is preferably equal to or higher than the temperature at which both components (A) and (B) melt, specifically preferably 40 to 95°C, more preferably 70 to 95°C.

[0048] <Container> Hereinafter, an embodiment of the 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.

[0049] The liquid dropper container for ophthalmic products of the present invention comprises a container body having a discharge outlet and a pressure-deformable portion, and a cap. 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.

[0050] 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.

[0051] 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.

[0052] 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.

[0053] 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.

[0054] 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.

[0055] 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.

[0056] 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.

[0057] 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.

[0058] 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.

[0059] 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.

[0060] 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 port 20 is a separate member from the inner plug member 14, a step of attaching the discharge port 20 to the inner plug member 14 is required, which is time-consuming during manufacturing. Therefore, from the viewpoint of manufacturing efficiency, it is preferable that the discharge port 20 is a molded body that is integrally molded from the same material as the inner plug member 14.

[0061] 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.

[0062] 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.

[0063] 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.

[0064] 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.

[0065] 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.

[0066] 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 .

[0067] 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.

[0068] 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.

[0069] 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.

[0070] 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.

[0071] 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.

[0072] 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 such that the volume decreases. 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.

[0073] 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 dripped from the outlet 20 when the pressure-deformation portion 30 is pressed from the first position A1 to the second position A2.

[0074] 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.

[0075] 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.

[0076] 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.

[0077] 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.

[0078] 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.

[0079] The above 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.

[0080] 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.

[0081] The amount of liquid dropped from the outlet 20 is 5 mm 3 Above 50mm 3 It is preferable that the volume is not more than 5 μL and not more than 50 μL. If the liquid content is eye drops (ophthalmic composition), one drop of liquid is 5mm 3 By keeping the volume at 50mm or more, the contents will be more likely to exert their full efficacy. 3 Doing the following will reduce the risk of the liquid dripping onto the eyeball overflowing. 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 reasons as above, the amount of liquid dropped from the discharge port 20 is preferably 5 mg or more and 50 mg or less, and more preferably 20 mg or more and 40 mg or less.

[0082] When the liquid content is an eye drop (ophthalmic composition), the volume 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 capacity of the container body 10 is preferably in the above range, and keeping the volume of the eye drops (ophthalmic composition) to 20 mL or less improves usability rather than reducing it in some cases. 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°.

[0083] 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.

[0084] Furthermore, by making the position of the outlet 20 of the pressure-deformation portion 30 the same in the thickness direction, when the pressure-deformation portion 30 is fixed in a position above the face and pressed with the index finger in the pressing direction 30A, 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.

[0085] 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.

[0086] As explained above, in the liquid dripping container 1 of this embodiment, the discharge port 20 and the pressure-deformation portion 30 are positioned above the center of the container body 10 in the vertical direction, and the first intersection angle θ1 between the pressing direction 30A of the pressure-deformation portion 30 and the discharge direction 20A of the liquid from the discharge port 20 is preferably 90° or more and less than 180°. Therefore, by pressing the pressure-deformation portion 30 formed of an elastic material in the pressing direction 30A, there is no need to adjust the amount of pressure, and during use, an appropriate amount of liquid can be quickly dripped onto the discharge target with a simple operation while the container body 10 is held in a comfortable position.

[0087] Furthermore, in the liquid dripping container 1 of this embodiment, an appropriate amount of one drop can be dripped by fully pressing the pressure-deforming portion 30, making it easier for the user to recognize the timing at which the liquid will be ejected and preventing an unnecessary amount of liquid from being dripped. Furthermore, in the liquid dripping container 1 of this embodiment, the second intersection angle θ2 is preferably set to be equal to or greater than 0° and less than 90°, so that the pressure-deformable portion 30 can be pressed in a more stable posture.

[0088] [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.

[0089] 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.

[0090] 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.

[0091] 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.

[0092] 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.

[0093] [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.

[0094] 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.

[0095] 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.

[0096] 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.

[0097] 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.

[0098] 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.

[0099] 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.

[0100] 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.

[0101] 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.

[0102] 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°.

[0103] 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°.

[0104] 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.

[0105] [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.

[0106] 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.

[0107] 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.

[0108] 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.

[0109] 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.

[0110] 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.

[0111] 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.

[0112] 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.

[0113] 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°.

[0114] 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°.

[0115] 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.

[0116] 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.

[0117] 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.

[0118] 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.

[0119] 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.

[0120] 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.

[0121] As described above, the liquid dispensing container for ophthalmic products of the present invention is a one-push type container that can dispense one drop of liquid from the discharge port 20 by pressing the pressure-deformable portion 30, which protrudes outward from the container body when not pressed, from the first position A1 to the second position A2. Therefore, the dispensing operation is highly reproducible. Furthermore, by blending (A) a nonionic surfactant and (B) an oily component into the ophthalmic composition contained in such a one-push container, it is possible to reduce variation in the amount of liquid ejected per drop.

[0122] <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.

[0123] <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.

[0124] 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, of 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, Ageless (registered trademark) (FX, SP, SS, SPE, ZP, Z-PT, Z-PKC, GLS, GL-M, Z-20PK) manufactured by Mitsubishi Gas Chemical Company, Inc., PharmaKeep, Vitalon manufactured by Tokiwa Sangyo Co., Ltd., Sansoles manufactured by Hakuyo Co., Ltd., WonderKeep manufactured by Powder Tech Co., Ltd., Sansocut manufactured by Iris Fine Products Co., Ltd., etc. can be used. (3) Containers with oxygen absorption capacity Specifically, for example, Oxyblock manufactured by Toyo Seikan Co., Ltd. can be used. (4) Oxygen-absorbing enclosure Specifically, Oxycatch (registered trademark) ICA manufactured by Kyodo Printing Co., Ltd., Cryovac (registered trademark) OS Film manufactured by Sealed Air Japan Co., Ltd., Hyster O2 manufactured by Star Plastics Industries Co., Ltd., Ageless Omac manufactured by Mitsubishi Gas Chemical Company, Inc., Oxydec manufactured by Toyo Seikan Co., Ltd., etc. can be used. The above means can be combined as appropriate, with (2) and (4) being preferred, and a combination of (1) and (2) and a combination of (1) and (4) being more preferred. [Example]

[0125] The present invention will be described in detail below with reference to examples, but the present invention is not limited to the following descriptions. The amounts of components used in each example are pure amounts unless otherwise specified.

[0126] <Measurement method> The pH was measured using a pH meter (manufactured by DKK-TOA Corporation, product name "HM-25R") The temperature of the ophthalmic composition to be measured was adjusted to 25°C, and the pH was measured. The viscosity was measured using a cone-plate type viscometer as a B-type rotational viscometer under the conditions of a measurement temperature of 25°C, a cone spindle CPA-42Z, a rotation speed of 50 RPM, and measurement after 1 minute.

[0127] <Evaluation method: Effect of improving the variation in drop amount> For each example of ophthalmic product, the container's discharge outlet was placed directly below, and the mass (unit: mg) of one drop discharged when the pressure-deforming portion (one-push button) was fully pressed once was measured. Two containers (n=2) were used, and measurements were repeated 10 times for each container (20 data points), and the standard deviation and coefficient of variation (CV, unit: %) of the mass of one drop were calculated. The coefficient of variation (CV) value was taken as the variation in the amount of one drop. The improvement rate (unit: %) in the variation of the amount of one drop was calculated using the following formula. Variation improvement rate=(variation in the amount of one drop of the corresponding comparative example−variation in the amount of one drop of the example) / variation in the amount of one drop of the corresponding comparative example×100

[0128] [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. <Component (A)> Polyoxyethylene hydrogenated castor oil 60 (trade name: HCO-60 (for pharmaceutical use), Nippon Surfactant Kogyo Co., Ltd., Pharmaceutical Additives Regulations), HLB: 14, IOB: 1.36. Polysorbate 80 (polyoxyethylene (20) sorbitan monooleate): (trade name: Rheodor TW-O120V, Kao Corporation, Japan Pharmacopoeia), HLB: 14, IOB: 1.39. Polyoxyethylene (196) polyoxypropylene (67) glycol (trade name: Kolliphor P407, BASF Japan Ltd., Pharmaceutical Additives Standards), HLB: 14, IOB: 1.34. Polyoxyl 40 stearate (polyethylene glycol 40 monostearate): (trade name: NIKKOL MYS-40MV, Nippon Surfactant Kogyo Co., Ltd., Japan Pharmacopoeia), HLB: 16, IOB: 1.57. Polyoxyethylene hydrogenated castor oil 40 (trade name: HCO-40 (for pharmaceutical use), Nippon Surfactant Kogyo Co., Ltd., Pharmaceutical Additives Regulations), HLB: 12, IOB: 1.21.

[0129] <(B) component> · Retinol palmitate: (Trade name: Retinol palmitate 1.74 million IU, with BHA / BHT added, DSM Co., Ltd., Japanese Pharmacopoeia), HLB: 1, IOB: 0.11. · d-α-Tocopherol acetate: (Trade name: RIKEN E acetate α, RIKEN Vitamin Co., Ltd., off-label), HLB: 2, IOB: 0.23. · Liquid paraffin: (Trade name: KAYDOL, Shima Trading Co., Ltd., Japanese Pharmacopoeia), HLB: 0, IOB: 0.00.

[0130] <(C) component> · Povidone (polyvinylpyrrolidone): (Trade name: Povidone K90 (Kollidon 90F), BASF Japan Ltd., Japanese Pharmacopoeia). · Hypromellose (hydroxypropylmethylcellulose): (Trade name: Methocel 60SH-4000, Shin-Etsu Chemical Co., Ltd., Japanese Pharmacopoeia). · Sodium hyaluronate purified (Trade name: Hyaluron San HA-AML, Kyuubi Co., Ltd., Japanese Pharmacopoeia). · Hydroxyethyl cellulose: (Trade name: NATROSOL, ASHLAND Co., Ltd., Japanese Pharmacopoeia).

[0131] <(D) component> · Boric acid: (Trade name: Boric acid, Kanto Chemical Co., Ltd., Japanese Pharmacopoeia). · Borax: (Borax (powder), Kosakai Pharmaceutical Co., Ltd., Japanese Pharmacopoeia). · Sodium edetate (EDTA): (Trade name: Sodium edetate hydrate "for manufacturing only", Fujifilm Wako Pure Chemical Corporation, Japanese Pharmacopoeia). · Trometamol: (Trade name: 2-Amino-2-hydroxymethyl-1,3-propanediol, Kanto Chemical Co., Ltd., off-label).

[0132] <pH adjuster> · Dilute hydrochloric acid: (Trade name: Dilute hydrochloric acid, Kosakai Pharmaceutical Co., Ltd., Japanese Pharmacopoeia). · Sodium hydroxide: (Trade name: Sodium hydroxide, Kosakai Pharmaceutical Co., Ltd., Japanese Pharmacopoeia). <Water> · Purified water.

[0133] <Other ingredients> Neostigmine methylsulfate (trade name: Neostigmine methylsulfate, Shionogi Pharma Co., Ltd., Japan Pharmacopoeia). Potassium L-aspartate (trade name: Potassium L-aspartate, Alps Pharmaceutical Co., Ltd., extra-governmental regulations). Taurine: Aminoethylsulfonic acid (trade name: Taurine, Three F Co., Ltd., JP). Berberine chloride hydrate (trade name: Japanese Pharmacopoeia Berberine Chloride Hydrate, Alps Pharmaceutical Co., Ltd., Japan Pharmacopoeia). Tetrahydrozoline hydrochloride (trade name: Tetrahydrozoline hydrochloride, Nippon Bulk Pharmaceutical Co., Ltd., extra-official regulations). Chlorpheniramine maleate (trade name: Chlorpheniramine maleate (Chlorpheniramine maleate), Kongo Chemical Co., Ltd., Japanese Pharmacopoeia). Epsilon aminocaproic acid (trade name: ε-amino-n-caproic acid EKD, Nippon Bulk Pharmaceutical Co., Ltd., Japan Pharmacopoeia). Dipotassium glycyrrhizinate (trade name: Dipotassium glycyrrhizinate, Maruzen Pharmaceutical Co., Ltd., non-regulated). Pyridoxine hydrochloride (trade name: Pyridoxine Hydrochloride, Pyridoxine Hydrochloride, BASF Japan Ltd., Japanese Pharmacopoeia). Chondroitin sulfate sodium (trade name: Non-regulated sodium chondroitin sulfate, Maruha Nichiro Corporation, non-regulated). Cyanocobalamin (trade name: Cyanocobalamin, DSM Co., Ltd., Japanese Pharmacopoeia).

[0134] [Examples 1 to 19, Comparative Examples 1 to 5] Ophthalmic compositions were prepared to have the compositions shown in Tables 1 to 4. Specifically, a mixed solution of components (A) and (B) was dissolved at 70 to 95°C to obtain mixture A (preliminary solution). Separately, aqueous solution B, prepared by mixing an aqueous solution (buffer solution) of component (D) and, if necessary, component (C), was heated to 70 to 95°C, and then mixture A and aqueous solution B were mixed. Next, the pH was adjusted to the pH (25°C) shown in the tables using dilute hydrochloric acid or sodium hydroxide as needed, and water was added as needed to adjust the total volume, thereby obtaining ophthalmic compositions. The obtained ophthalmic compositions were filled into containers (one-push containers) having the configurations shown in Figures 6 to 8 to obtain ophthalmic products. The container body was made of polyethylene terephthalate resin (PET), the protrusions were made of polypropylene resin (PP), the pressure-deformable portion was made of styrene-based elastomer, and the discharge port was made of polypropylene resin (PP). The container body had a capacity of 20 mL, and the amount of ophthalmic composition filled was 15 mL. The effect of reducing the variation in the amount of each drop was evaluated using the above method. The results are shown in the table below. In the table, the "appropriate amount" of the content of the pH adjuster means the amount required to adjust the pH of the ophthalmic composition of each example at 25°C to the value shown in the table. The viscosity was 1.2 to 1.4 mPa·s in Examples 1 to 15 and 19 and Comparative Examples 1 and 2. The viscosity of the other Examples and Comparative Examples is as shown in the table.

[0135] [Table 1]

[0136] [Table 2A]

[0137] [Table 2B]

[0138] [Table 3]

[0139] [Table 4]

[0140] As shown in the results in Tables 1 to 4, Examples 1 to 15 and Example 19, in which the ophthalmic compositions contained the components (A) and (B), showed improved variation in the amount per drop compared to Comparative Example 1, which did not contain the components (A) and (B), and the Comparative Example, which did not contain the component (B). Furthermore, Examples 16, 17, and 18, in which the ophthalmic compositions contained components (A), (B), and (C), showed improved variation in the amount per drop compared to Comparative Examples 3, 4, and 5, in which component (B) was not contained.

[0141] Formulation examples of ophthalmic compositions are shown in Tables 5 and 6. The unit of content of each component is w / v % unless otherwise specified.

[0142] [Table 5]

[0143] [Table 6] [Explanation of symbols]

[0144] 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 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, An ophthalmic product, wherein the ophthalmic composition comprises (A) a nonionic surfactant and (B) an oily component.

2. 2. The ophthalmic product according to claim 1, wherein the component (B) is at least one selected from the group consisting of vitamin A, vitamin E, liquid paraffin, sesame oil, and castor oil.

3. 2. The ophthalmic product according to claim 1, wherein the component (A) is at least one selected from the group consisting of polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene polyoxypropylene glycol, and polyethylene glycol fatty acid ester.

4. 2. The ophthalmic product according to claim 1, further comprising (C) a water-soluble polymer, wherein the water-soluble polymer is at least one selected from the group consisting of polyvinylpyrrolidone, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, hydroxyethyl cellulose, methyl cellulose, polyvinyl alcohol, hyaluronic acid and its salts, and carboxyvinyl polymers.

5. The ophthalmic product according to claim 1, further comprising (D) one or more members selected from the group consisting of boric acid, borax, trometamol, and ethylenediamineacetic acid derivatives and salts thereof, and having a pH of 5 to 7.5 at 25°C.

6. The ophthalmic product according to any one of claims 1 to 5, wherein the amount of one drop of the ophthalmic composition dispensed from the discharge port is 5 mg to 50 mg.

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