Eyelid cleaning composition

Abstract

The present disclosure aims to provide an eyelid wiping composition that has excellent elution properties for a glaucoma treatment drug and can remove the glaucoma treatment drug, or an eyelid wiping tool in which the composition is impregnated into a wiping tool. [Solution] The eyelid wiping composition contains a nonionic surfactant and is used to wipe away glaucoma treatment drugs.

Description

[Technical Field]

[0001] The present disclosure relates to eyelid wiping compositions and the like. [Background technology]

[0002] Glaucoma is an eye disease that is said to affect one in 20 Japanese people over the age of 40, and is one of the leading causes of blindness. Eye drops are the primary treatment for glaucoma.

[0003] However, it has been reported that the use of glaucoma eye drops can cause side effects in the eyelid area (around the eyes), such as eyelid pigmentation, excessive eyelashes, increased vellus hair, and blepharitis (e.g., Non-Patent Document 1).

[0004] These side effects can be reduced by quickly removing the drug (antiglaucoma drug) from the affected area, especially the eyelid area, after instillation.

[0005] Therefore, it is recommended to wipe off any glaucoma eye drops adhering to the eyelids with tissue paper or the like during or after administration. Nevertheless, the reason why side effects such as eyelid pigmentation have been reported is thought to be that simply wiping the glaucoma eye drops off the eyelids with tissue paper is not effective enough to remove the glaucoma medication.

[0006] Incidentally, cleansing cotton has been commercially available for use on the eyelids (around the eyes). Examples of such cleansing cotton include absorbent cotton containing a solution of purified water with a preservative added, and cleansing cotton made from purified water without adding a preservative and sterilized under high pressure.

[0007] However, these cleansing cotton pads are intended to keep the area around the eyes clean or to remove eye discharge. Therefore, commercially available cleansing cotton pads are not designed to remove specific medications (antiglaucoma medications), and therefore have little ability to remove medications that have adhered to the skin after using glaucoma eye drops. Therefore, there is a demand for a composition for wiping the eyelids, which can be impregnated into a wipe such as cleansing cotton and has a high ability to remove glaucoma medications. [Prior art documents] [Non-patent literature]

[0008] [Non-Patent Document 1] Kenji Inoue et al., Local side effects in patients using latanoprost, Journal of the Japanese Ophthalmological Association 110(8), pp.581-587(2006). Summary of the Invention [Problem to be solved by the invention]

[0009] The present disclosure aims to provide an eyelid wiping composition that has excellent elution properties for a glaucoma treatment drug and can remove the glaucoma treatment drug, or an eyelid wiping tool in which the composition is impregnated into a wiping tool. [Means for solving the problem]

[0010] As a result of extensive research, the present inventors have found that an eyelid wiping composition containing a nonionic surfactant can solve the above-mentioned problems. The present disclosure has been completed based on this finding.

[0011] That is, the present disclosure is as follows. Section 1. A composition for wiping the eyelid containing a nonionic surfactant, A composition for wiping the eyelids, used for wiping a glaucoma treatment drug. Section 2. Item 1. The eyelid wiping composition according to Item 1, which is used to dissolve and remove a therapeutic drug for glaucoma. Section 3. Item 1. The composition for wiping the eyelid according to Item 1, wherein the composition for wiping the eyelid does not contain a therapeutic drug for glaucoma. Section 4. Item 2. The eyelid wiping composition according to Item 1, wherein the nonionic surfactant comprises an ester-type nonionic surfactant. Section 5. Item 1. The eyelid wiping composition according to Item 1, wherein the nonionic surfactant comprises at least one compound selected from the group consisting of polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan fatty acid esters (polysorbates), and sucrose fatty acid esters. Section 6. Item 2. The composition for wiping the eyelid according to Item 1, wherein the therapeutic drug for glaucoma is a prostaglandin F2α derivative or a Rho kinase inhibitor. Section 7. Item 2. The composition for wiping the eyelid according to Item 1, wherein the therapeutic drug for glaucoma is a prostaglandin F2α derivative. Section 8. Item 1. The eyelid wiping composition according to Item 1, further comprising cyclodextrin. Section 9. Item 9. An eyelid wiping tool comprising a wiping tool impregnated with the eyelid wiping composition according to any one of Items 1 to 8. Section 10. Item 9. A method for wiping an eyelid, comprising wiping the eyelid with the composition for wiping an eyelid according to any one of Items 1 to 8. Section 11. 1. A method for preventing side effects in a patient using a glaucoma medication, comprising: Item 10. A method for preventing side effects of a glaucoma treatment drug, comprising a step of wiping the eyelid using the eyelid wiping tool according to Item 9. [Effects of the Invention]

[0012] According to the present disclosure, it is possible to provide an eyelid wiping composition that has excellent elution properties for a glaucoma treatment drug and can remove the glaucoma treatment drug, or an eyelid wiping tool in which the composition is impregnated into a wiping tool. DETAILED DESCRIPTION OF THE INVENTION

[0013] Composition for cleaning eyelids The eyelid wiping composition of the present disclosure contains a nonionic surfactant. The eyelid wiping composition of the present disclosure can be used to wipe away glaucoma treatment drugs. The eyelid wiping composition of the present disclosure is characterized by not containing a glaucoma treatment drug. The eyelid wiping composition of the present disclosure can be rephrased as a skin wiping composition, a composition for preventing eyelid pigmentation, a composition for preventing excessive eyelash growth, a composition for preventing the increase of vellus hair, a composition for preventing blepharitis, etc. Prevention also includes the meanings of suppression, reduction, alleviation, etc.

[0014] Nonionic surfactants The nonionic surfactant is not particularly limited, and examples thereof include polyoxyethylene hydrogenated castor oils such as polyoxyethylene (5) hydrogenated castor oil, polyoxyethylene (7) hydrogenated castor oil, polyoxyethylene (10) hydrogenated castor oil, polyoxyethylene (20) hydrogenated castor oil, polyoxyethylene (30) hydrogenated castor oil, polyoxyethylene (40) hydrogenated castor oil, polyoxyethylene (50) hydrogenated castor oil, polyoxyethylene (60) hydrogenated castor oil, and polyoxyethylene (100) hydrogenated castor oil; sorbitan monooleate, and monostearin. Sorbitan fatty acid esters such as sorbitan acid; polysorbate 20 (polyoxyethylene sorbitan monolaurate (20E.O.), Tween® 20 (CAS number: 9005-64-5)), polysorbate 21 (mainly sorbitol and sorbitol anhydride lauric acid monoesters obtained by addition polymerization of about 4 moles of ethylene oxide, Tween® 21 (CAS number: 9005-64-5 (generic))), polysorbate 40 (polyoxyethylene sorbitan monopalmitate (20E.O.), Tween n (registered trademark) 40 (CAS number: 9005-66-7)), polysorbate 60 (polyoxyethylene sorbitan monostearate, Tween (registered trademark) 60 (CAS number: 9005-67-8)), polysorbate 61 (mainly sorbitol and sorbitol anhydride lauric acid monoesters with approximately 4 moles of ethylene oxide, Tween (registered trademark) 61 (CAS number: 9005-67-8 (generic))), polysorbate 65 (polyoxyethylene sorbitan tristearate (20 E.O.), Tween n (registered trademark) 65 (CAS number: 9005-71-4)), Polysorbate 80 (polyoxyethylene sorbitan monooleate (20 E.O.), Tween (registered trademark) 80 (CAS number: 9005-65-6)), Polysorbate 81 (mainly sorbitol and sorbitol anhydride oleic acid monoesters polymerized with approximately 5 moles of ethylene oxide, Tween (registered trademark) 81 (CAS number: 9005-65-6 (generic))), Polysorbate 85 (polyoxyethylene sorbitan trioleate (20 E.O.)Polyoxyethylene sorbitan fatty acid esters such as Tween® 85 (CAS number: 9005-70-3) (polyoxyethylene sorbitan fatty acid esters are sorbitan fatty acid esters to which a polyoxyethylene chain has been added, and are also called polysorbates); polyoxyethylene trimethylolpropane fatty acid esters such as polyoxyethylene (8) trimethylolpropane trimyristate, polyoxyethylene (20) trimethylolpropane trimyristate, and polyoxyethylene (30) trimethylolpropane trimyristate; polyoxyethylene sorbitol fatty acid esters such as polyoxyethylene (30) sorbitol tetraoleate and polyoxyethylene (40) sorbitol tetraoleate; polyoxyethylene fatty acid esters such as polyoxyethylene (6) diisostearate and polyoxyethylene (12) diisostearate; sucrose erucate, sucrose stearate, sucrose palmitate, sucrose myristate, sucrose oleate, sucrose laurate ... Sucrose fatty acid esters such as sugar behenate (e.g., C10-25 saturated or unsaturated fatty acid esters of sucrose); glycerin fatty acid esters such as diglycerin monostearate; polyoxyethylene (3) glyceryl monoisostearate, polyoxyethylene (6) glyceryl monoisostearate, polyoxyethylene (8) glyceryl monoisostearate, polyoxyethylene (10) glyceryl monoisostearate, polyoxyethylene (15) glyceryl monoisostearate, polyoxyethylene (20) glyceryl Examples of suitable surfactants include ester-type nonionic surfactants such as polyoxyethylene glycerin fatty acid esters, such as polyoxyethylene (30) glyceryl monoisostearate, polyoxyethylene (10) glyceryl triisostearate, polyoxyethylene (20) glyceryl triisostearate, polyoxyethylene (30) glyceryl triisostearate, and polyoxyethylene (40) glyceryl triisostearate; ether-type nonionic surfactants; and ether-ester-type nonionic surfactants.

[0015] Among these, preferred nonionic surfactants are polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan fatty acid esters, and sucrose fatty acid esters, and more preferred are polyoxyethylene hydrogenated castor oil and polyoxyethylene sorbitan fatty acid esters. These nonionic surfactants can be used either alone or in combination of two or more.

[0016] The nonionic surfactant is preferably a composition containing two or more nonionic surfactants, more preferably a composition containing a surfactant having a polyoxyethylene group and a polysorbate.

[0017] The concentration of the nonionic surfactant is not particularly limited. The lower limit of the concentration of the nonionic surfactant is, for example, 0.1 mg / mL or more, 0.2 mg / mL or more, 0.3 mg / mL or more, 0.4 mg / mL or more, 0.5 mg / mL or more, 1.0 mg / mL or more, 1.5 mg / mL or more, or 2.0 mg / mL or more. The upper limit of the concentration of the nonionic surfactant is, for example, 500 mg / mL or less, 300 mg / mL or less, 200 mg / mL or less, 100 mg / mL or less, 50 mg / mL or less, 30 mg / mL or less, or 20 mg / mL or less. The concentration of the nonionic surfactant is not particularly limited, and is, for example, 0.1 mg / mL to 500 mg / mL, 0.2 mg / mL to 300 mg / mL, 0.3 mg / mL to 200 mg / mL, 0.4 mg / mL to 150 mg / mL, 0.5 mg / mL to 100 mg / mL, 0.5 mg / mL to 50 mg / mL, 1.0 mg / mL to 30 mg / mL, 1.0 mg / mL to 20 mg / mL, 1.5 mg / mL to 20 mg / mL, 2.0 mg / mL to 20 mg / mL, 1.0 mg / mL to 15.0 mg / mL, or 2.0 mg / mL to 10.0 mg / mL.

[0018] Glaucoma medication The eyelid wiping composition of the present disclosure is used for wiping the eyelid with a glaucoma treatment drug, which can be referred to as an active ingredient, a side effect ingredient, or the like. Medication for treating glaucoma is not particularly limited, and examples thereof include prostaglandin derivatives, which are drugs primarily intended to reduce intraocular pressure; Rho kinase inhibitors (e.g., ROCK inhibitors such as ripasudil and netarsudil); beta-blockers (e.g., Timoptol (timolol maleate), Rismon TG (timolol maleate), Mikelan (carteolol hydrochloride), etc.); alpha-2 receptor agonists (e.g., brimonidine); and carbonic anhydrase inhibitors (e.g., dorzolamide, acetazolamide, brinzolamide, etc.). The glaucoma eye drops contain a therapeutic drug for glaucoma and other known optional ingredients used in eye drops. The glaucoma eye drops can also be referred to as glaucoma eye drops, etc.

[0019] A prostaglandin derivative refers to a prostaglandin or a prostaglandin analogue that exhibits an effect equivalent to that of a prostaglandin, or a pharmaceutical product (drug) containing a pharmaceutically acceptable salt thereof. Prostaglandin derivatives are used to treat glaucoma through the alternative pathway (via the uveoscleral flow) by promoting aqueous humor outflow. Examples of prostaglandin derivatives include, but are not limited to, prostaglandin F2α derivatives (PGF2α) such as latanoprost, tafluprost, travoprost, and isopropyl unoprostone; prostamide derivatives; and the like. Preferred prostaglandin derivatives include, for example, prostaglandin F2α derivatives such as latanoprost, tafluprost, and travoprost; prostamide derivatives; and the like.

[0020] In the prostaglandin F2α derivative-containing product as a therapeutic drug for glaucoma, the prostaglandin is preferably present in a state of being dissolved in water. The concentration of the prostaglandin in the aqueous solution may be appropriately selected taking into consideration the intended use of the aqueous solution. For example, in the case of eye drops, the concentration of the prostaglandin in the eye drops may be appropriately selected depending on the target disease, symptoms, etc., and may be, for example, 0.00005 to 0.05%. It has been reported that the use of glaucoma treatment drugs can cause side effects in the eyelid area (around the eyes), such as eyelid pigmentation, excessive eyelashes, increased vellus hair, and blepharitis (e.g., Non-Patent Document 1). For example, prostaglandin derivatives have been reported to cause side effects such as iris pigmentation, eyelid pigmentation, excessive eyelashes, and increased vellus hair. Known side effects of Rho kinase inhibitors include conjunctival congestion, conjunctivitis including allergic conjunctivitis, and blepharitis including allergic conjunctivitis.

[0021] Optional ingredients The eyelid wiping composition of the present disclosure may further contain optional components in addition to the nonionic surfactant.

[0022] Optional ingredients include, for example, cyclodextrin; cationic surfactants; anionic surfactants; amphoteric surfactants; antioxidants; tonicity adjusting agents; buffers; preservatives; and the like.

[0023] Cyclodextrins (hereinafter sometimes referred to as "CD") are cyclic oligosaccharides formed from glucose molecules connected via α-1,4-glucosidic bonds, and include a Greek letter as a prefix depending on the number of glucose molecules that make up the cyclodextrin. Such cyclodextrins are not particularly limited, and examples thereof include α-cyclodextrin having six glucose molecules, β-cyclodextrin having seven glucose molecules, γ-dextrin having eight glucose molecules, and δ-cyclodextrin having nine glucose molecules. α-cyclodextrin is preferred as the cyclodextrin (CD). These may be used alone or in combination of two or more. The content of cyclodextrin in the eyelid wiping composition is usually 0.1 to 10,000 parts by mass, preferably 1 to 1,000 parts by mass, and more preferably 50 to 500 parts by mass, relative to 100 parts by mass of the nonionic surfactant.

[0024] The cationic surfactant is not particularly limited, and examples thereof include cetylpyridinium chloride, benzalkonium chloride, and benzethonium chloride.

[0025] The anionic surfactant is not particularly limited, and examples thereof include alkylbenzene sulfonates, alkyl sulfates, polyoxyethylene alkyl sulfates, aliphatic α-sulfomethyl esters, and α-olefin sulfonic acids.

[0026] The amphoteric surfactant is not particularly limited, and examples thereof include alkyldiaminoethylglycine or a salt thereof (for example, hydrochloride).

[0027] The antioxidant is not particularly limited, and examples thereof include ethylenediaminetetraacetic acid, dibutylhydroxytoluene, and the like.

[0028] The isotonic agent is not particularly limited, and examples thereof include sodium chloride, potassium chloride, calcium chloride, glycerin, and propylene glycol.

[0029] The buffering agent is not particularly limited, and examples thereof include boric acid, borax, citric acid, disodium hydrogen phosphate, and ε-aminocaproic acid.

[0030] The preservative is not particularly limited, and examples thereof include benzalkonium chloride, chlorhexidine gluconate, benzethonium chloride, sorbic acid, potassium sorbate, ethyl parahydroxybenzoate, butyl parahydroxybenzoate, etc. Note that benzalkonium chloride, chlorhexidine gluconate, and benzethonium chloride also function as cationic surfactants.

[0031] The content of optional components in the eyelid wiping composition is not particularly limited. When optional components are blended, the content of the optional components is, for example, usually 0.001 to 10,000 parts by mass, preferably 0.01 to 1,000 parts by mass, and more preferably 0.1 to 500 parts by mass, relative to 100 parts by mass of the nonionic surfactant.

[0032] The eyelid wiping composition of the present disclosure may further contain ethanol. When ethanol is contained in the eyelid wiping composition of the present disclosure, there is no particular problem with the concentration of ethanol as long as it is not irritating to the skin, and for example, it is about 0.001 to 10% by volume or less, preferably 0.01 to 8% by volume, and more preferably about 0.1 to 5% by volume.

[0033] The eyelid wiping composition of the present disclosure can contain polyethylene glycol, in particular, to enable a smooth wiping operation and reduce catching on the skin when the composition is impregnated into a wipe such as cotton and used to wipe the skin.

[0034] The average molecular weight of the polyethylene glycol used in the present disclosure is not particularly limited, and for example, polyethylene glycol 300, polyethylene glycol 400, polyethylene glycol 600, polyethylene glycol 1000, polyethylene glycol 1500, polyethylene glycol 1540, polyethylene glycol 2000, polyethylene glycol 3350, polyethylene glycol 4000, polyethylene glycol 6000, polyethylene glycol 8000, polyethylene glycol 9000, polyethylene glycol 11000, polyethylene glycol 12000, polyethylene glycol 20000, and the like can be used. Among these polyethylene glycols, from the viewpoint of more effectively reducing the likelihood of the product catching on the skin during wiping, preferred are polyethylene glycol 400, polyethylene glycol 600, polyethylene glycol 1000, polyethylene glycol 1500, polyethylene glycol 1540, polyethylene glycol 2000, polyethylene glycol 3350, polyethylene glycol 4000, polyethylene glycol 6000, polyethylene glycol 8000, and polyethylene glycol 9000; more preferred are polyethylene glycol 600, polyethylene glycol 1000, polyethylene glycol 1500, polyethylene glycol 1540, polyethylene glycol 2000, polyethylene glycol 3350, polyethylene glycol 4000, and polyethylene glycol 6000; and particularly preferred are polyethylene glycol 1500, polyethylene glycol 1540, polyethylene glycol 2000, polyethylene glycol 3350, and polyethylene glycol 4000.

[0035] When polyethylene glycol is blended into the eyelid wiping composition of the present disclosure, there is no particular problem with the concentration of polyethylene glycol as long as it is at a level that does not cause skin irritation, and it is, for example, about 0.001 to 15% by mass or less, preferably 0.01 to 10% by mass, and more preferably about 0.1 to 8% by mass. Furthermore, when polyethylene glycol is blended into the eyelid wiping composition of the present disclosure, the content of polyethylene glycol is, for example, usually 0.1 to 1000 parts by mass, preferably 1 to 500 parts by mass, and more preferably 10 to 200 parts by mass, relative to 100 parts by mass of the nonionic surfactant.

[0036] The eyelid wiping composition of the present disclosure may further contain propylene glycol. When propylene glycol is blended into the eyelid wiping composition of the present disclosure, the concentration of propylene glycol is not particularly problematic as long as it is not irritating to the skin, and is, for example, about 0.001 to 15% by mass or less, preferably 0.01 to 10% by mass, and more preferably about 0.1 to 8% by mass. Furthermore, when propylene glycol is blended into the eyelid wiping composition of the present disclosure, the content of propylene glycol is, for example, typically 0.1 to 1000 parts by mass, preferably 1 to 500 parts by mass, and more preferably 10 to 200 parts by mass, relative to 100 parts by mass of the nonionic surfactant.

[0037] The eyelid wiping composition of the present disclosure may further contain glycerin. When glycerin is blended into the eyelid wiping composition of the present disclosure, the concentration of glycerin is not particularly problematic as long as it is not irritating to the skin, and is, for example, about 0.001 to 15% by mass or less, preferably 0.01 to 10% by mass, and more preferably about 0.1 to 8% by mass. Furthermore, when glycerin is blended into the eyelid wiping composition of the present disclosure, the content of glycerin is, for example, usually 0.1 to 1000 parts by mass, preferably 1 to 500 parts by mass, and more preferably 10 to 200 parts by mass, relative to 100 parts by mass of the nonionic surfactant.

[0038] The eyelid wiping composition of the present disclosure preferably contains water as a base, and the water is not particularly limited, and examples thereof include ordinary tap water, purified water, and distilled water.

[0039] In addition to the components described above, the eyelid wiping composition of the present disclosure may contain, as necessary, pharmacological ingredients, additives, etc. that are used in ordinary eyelid wiping compositions.

[0040] Examples of pharmacological ingredients that can be incorporated into the eyelid wiping composition of the present disclosure include antibacterial or disinfectant agents, antihistamines, local anesthetics, anti-inflammatory agents, skin protectants, cooling agents, mucopolysaccharides, etc. These pharmacological ingredients may be used alone or in combination of two or more. When these pharmacological ingredients are contained, the content thereof may be appropriately determined depending on the type of pharmacological ingredient used, the expected effect, etc.

[0041] Examples of additives that can be incorporated into the eyelid wiping composition of the present disclosure include monohydric lower alcohols other than ethanol, polyhydric alcohols other than those mentioned above, flavoring agents, colorants, thickeners, pH adjusters, humectants, stabilizers, antioxidants, UV absorbers, chelating agents, adhesives, buffers, solubilizers, and the like. These additives may be used alone or in combination of two or more. The content of these additives can be appropriately determined depending on the formulation, etc.

[0042] Formulation The form of the eyelid wiping composition of the present disclosure is not particularly limited, but it is preferably in a form that is easy to use for wiping the eyelid, particularly in a form that is easy to impregnate into a wiping tool, and specifically, it is preferably in a liquid or semi-solid form (such as a gel, ointment, or paste).

[0043] Specific examples of the formulation of the eyelid wiping composition of the present disclosure include liquids, lotions, emulsions, gels, ointments, creams, etc. Among these formulations, liquids and lotions are preferred.

[0044] The eyelid wiping composition of the present disclosure is used to wipe the eyelids in order to reduce the side effects of glaucoma treatment drugs. The method for wiping the eyelids using the eyelid wiping composition of the present disclosure is not particularly limited, but it is preferable to blend an appropriate amount into a wiper, for example, to impregnate the wiper, and then wipe the eyelids.

[0045] Cleaning tools The wiping implement to be impregnated with the eyelid wiping composition of the present disclosure may be any implement that can be used to wipe the eyelid, and examples thereof include cotton, puffs, nonwoven fabric sheets, woven fabric sheets (such as gauze), sponges, etc. The constituent materials of these wiping implements are not particularly limited and may be, for example, natural fibers, recycled fibers, semi-synthetic fibers, synthetic fibers, synthetic resins, etc., but from the viewpoint of the feel when wiping, natural fibers are preferred, and cotton is more preferred. The wipe impregnated with the eyelid wiping composition of the present disclosure can also be referred to as an eyelid wet wiper, cleansing cotton, or the like.

[0046] The eyelid wiping composition of the present disclosure is used to wipe away glaucoma medication. The eyelid wiping composition of the present disclosure is intended to dissolve and remove a glaucoma treatment drug adhered to the eyelid. Here, "dissolving and removing" can be rephrased as "dissolving and removing," "eluting," "removing," etc.

[0047] The eyelid cleansing composition of the present disclosure comprises a nonionic surfactant and is for use in a method for preventing side effects in patients using glaucoma medications as first-line medications.

[0048] Eyelid cleaning tool The eyelid wiping tool of the present disclosure contains the nonionic surfactant. Specifically, the eyelid wiping tool of the present disclosure is, for example, a wiper impregnated with the eyelid wiping composition.

[0049] Eyelid wiping method The method for wiping the eyelid of the present disclosure is a method for wiping the eyelid using a wiper impregnated with the composition for wiping the eyelid.

[0050] How to prevent side effects The present disclosure includes a method for preventing side effects of a patient using a glaucoma treatment drug, the method comprising a step of wiping the eyelid using the eyelid wiping device. [Example]

[0051] The present disclosure will be explained in more detail below using examples, but the technical scope of the present disclosure is not limited to these examples.

[0052] Experimental Method A Toyo filter paper No. 7 (1x2cm, 2cm) was placed in a 20mL screw tube bottle (sample tube). 2 ) was placed in the sample tube. 50 μL of the drug solution was then dropped onto the filter paper, and the drug solution was allowed to soak into the filter paper and left for approximately 30 minutes. Next, 400 μL of the test solution was placed in the sample tube, and the sample tube was capped. The contents were then gently stirred for 5 minutes. 50 μL of the sample was then sampled from the sample tube. The diluted solution and internal standard solution were added to this sampled solution and stirred. After stirring, this solution was injected into HPLC. A standard solution for quantification was prepared as follows: 400 μL of a 1:1 methanol:water solution was added to 50 μL of the drug solution and stirred well. 50 μL of this solution was sampled, and the diluted solution and internal standard solution were added and stirred. After stirring, this solution was injected into HPLC. The dissolution rate of the drug in each test solution was calculated by setting the peak area ratio of the standard solution as 100%.

[0053] Drug quantification methods The drug was quantified using HPLC (High Performance Liquid Chromatography) under the following conditions. HPLC used: Shimadzu LC-10 system (Constituent equipment: Pump: LC-10AS, UV detector: SPD-10AS, Column oven: CTO-10A, Auto injector: SIL-10A, Controller: SCL-10A, Chromatopac: C-R7A Plus) HPLC column: YMC Co., Ltd., C18 column YMC-Pack ODS-AM12S05 (150 x 6 mm, ID particle size 5 μm) Mobile phase flow rate: 1 mL / min, column temperature: 40°C

[0054] Test Example 1 (Preliminary test: Search for eluate) The elution rate of the antiglaucoma drug into the elution solution was measured according to the above-mentioned Experimental Method A. (glaucoma treatment drug) Latanoprost PF ophthalmic solution 0.005% (Nitten), Japan Eye Drop Research Institute Co., Ltd. (Elution solution raw material) Water (purified water produced at Tokushima Bunri University) Ethanol (Fujifilm Wako Pure Chemical Industries, purity 99.5%) α-Cyclodextrin (Wako Pure Chemical Industries, Ltd.) Polyethylene glycol (Macrogol (registered trademark) 400) (Wako Pure Chemical Industries, Ltd.) Glycerin (Wako Pure Chemical Industries, Ltd.) Polyvinyl alcohol (Nippon Synthetic Chemical Industry Co., Ltd., product name: GOHSENOL (registered trademark) EG-05) Propylene glycol (Wako Pure Chemical Industries, Ltd.) Polyoxyethylene hydrogenated castor oil (Nikko Chemicals Co., Ltd., product name: NIKKOL® HCO-60) Polysorbate 80 (Nikko Chemicals Co., Ltd., product name: NIKKOL (registered trademark) TO-10v) The polyethylene glycol, glycerin, polyvinyl alcohol, and propylene glycol were used as solvents that are highly miscible with water and have a proven track record in eye drops.

[0055] The following drug solutions, test solutions, dilution solutions, and internal standard solutions were used, and the experiment was carried out according to the above-mentioned Experimental Method A. Then, HPLC was measured under the HPLC conditions shown below to determine the dissolution rate of the drug. Drug solution: Glaucoma treatment drug (Latanoprost PF eye drops 0.005% "Nitten", Nippon Eye Drops Co., Ltd.) Test solution: 400 μL of water or aqueous solution shown in Table 1 below (Samples 1-1 to 1-11) Dilution solution: 50 μL of methanol Internal standard solution: 100 μL of 20 μg / mL butylparaben solution dissolved in methanol:water = 1:1

[0056] HPLC conditions ·Mobile phase composition: CH3CN:H2O:HClO4:NaClO4=625:375:1:5(W / W / W / V) Detection wavelength: 260nm ·Injection volume: 50μL Internal standard solution: butylparaben 20 μg / mL

[0057] The test solutions shown in Table 1 were dropped onto filter paper in accordance with the above-mentioned Experimental Method A to elute the glaucoma treatment drug, and the removal effect of the glaucoma treatment drug was expressed as the elution rate (hereinafter, common to all test examples).

[0058] [Table 1]

[0059] result As a result, the highest dissolution rates were observed for 80% ethanol (97.9%), α-cyclodextrin (α-CD) at 100 mg / mL (81.9%), the nonionic surfactant polyoxyethylene hydrogenated castor oil at 10 mg / mL (72.4%), and the nonionic surfactant polysorbate 80 at 5 mg / mL (80.7%). This test revealed that nonionic surfactants can be used as a solvent when impregnated into cleansing cotton, etc., and can dissolve glaucoma medications and remove them from the eyelids. Although 80% ethanol has a high dissolution rate, it can cause severe eye irritation and may affect the skin of people with alcohol allergies, so it is considered best not to use it.

[0060] Test Example 2 (Preliminary test: elution test using commercially available wipes) Dissolution rate of solution contained in cleansing cotton used around the eyes The following drug solutions, test solutions, dilution solutions, and internal standard solutions were used, and the experiment was carried out according to the above-mentioned Experimental Method A. Then, HPLC was measured under the HPLC conditions shown below to determine the dissolution rate of the drug. The drug solution used was a glaucoma treatment drug (Latanoprost (Tokyo Chemical Industry Co., Ltd.)) purchased as a reagent, diluted with a solution of acetonitrile (CH3CN):water (HO) = 1:9, to a concentration (0.005%) similar to that of eye drops. The acetonitrile used was manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. (for HPLC reagents), and purified water was used. The diluted solution used was 50 μL of methanol. The internal standard solution used was 100 μL of a 20 μg / mL butylparaben solution dissolved in methanol:water=1:1. The test solutions used were obtained by squeezing out the solutions contained in Sample 2-1 (product name: Wipe-off I-Cotton, Kawamoto Sangyo Co., Ltd.), Sample 2-2 (product name: I-Jou-Wat (registered trademark), Hakujuji Co., Ltd.), and Sample 2-3 (product name: Wipe-off Cleaning Cotton, Daiei Co., Ltd.), which are commercially available wipes. In addition, the n number is 6 in Samples 2-1 and 2-3, and the n number is 5 in Sample 2-2.

[0061] HPLC conditions for latanoprost ·Mobile phase composition: CH3CN:H2O:HClO4:NaClO4= 625:375:1:5(W / W / W / V) Detection wavelength: 260nm ·Injection volume: 50μL Internal standard solution: butylparaben 20 μg / mL

[0062] The results are shown in Table 2 below.

[0063] [Table 2]

[0064] result As a result, the dissolution rates of all glaucoma medications were found to be below 70.6%. Therefore, it became clear that it was necessary to develop a formulation with a dissolution rate of over 70.6%.

[0065] Test Example 3 (Dissolution test: Examination of the relationship between compounds with different solubilities and surfactants) The compounds, surfactants (nonionic surfactants, cationic surfactants, anionic surfactants), and solvents used were as follows: (compound) Compound 1: Antiglaucoma drug: Latanoprost (Tokyo Chemical Industry Co., Ltd., reagent) (solubility: 50 μg / mL) Compound 2: Fluticasone propionate (Apple Pharmaceutical Co., Ltd.) (solubility: 0.1 μg / mL) Compound 3: Hydrocortisone (Fujifilm Wako Pure Chemical Industries, Ltd., reagent) (solubility: 0.58 mg / mL) Compound 4: Ketotifen fumarate (Sigma-Aldrich, reagent) (solubility: 16.1 mg / mL) Compound 5: Flavin adenine dinucleotide (Fujifilm Wako Pure Chemical Industries, Ltd., reagent) (solubility: >100 mg / mL) (nonionic surfactants) Polyoxyethylene hydrogenated castor oil (Nikko Chemicals Co., Ltd., product name: NIKKOL® HCO-60) Polysorbate 80 (Nikko Chemicals Co., Ltd., product name: NIKKOL (registered trademark) TO-10v) Polysorbate 20 (Sigma-Aldrich, reagent) Sucrose fatty acid ester (Tokyo Chemical Industry Co., Ltd., reagent) (cationic surfactant) Benzalkonium chloride (Kenei Pharmaceutical Co., Ltd., product name: Zalcon Liquid P) (anionic surfactants) Sodium oleate (Wako Pure Chemical Industries, Ltd., reagent) Sodium lauryl sulfate (Fujifilm Wako Pure Chemical Industries, Ltd., Reagent) (solvent) Ethanol (Fujifilm Wako Pure Chemical Industries, purity 99.5%) ·Water (purified water)

[0066] The following drug solutions, test solutions, dilution solutions, and internal standard solutions were used, and the experiment was carried out according to the above-mentioned Experimental Method A. Then, HPLC was measured under the HPLC conditions shown below to determine the dissolution rate of the drug. As test solutions, aqueous solutions of surfactants shown in Table 3 below were used (Samples 3-1 to 3-13). The drug solution, dilution solution, and internal standard solution for each compound, as well as the HPLC conditions, are shown below.

[0067] Latanoprost (Compound 1) Drug solution: Latanoprost (Tokyo Chemical Industry Co., Ltd.) diluted with acetonitrile (CH3CN):water (H2O) = 1:9 to a solution prepared to the same concentration (0.005%) as eye drops. Dilution solution: 50 μL of methanol Internal standard solution: 100 μL of 20 μg / mL butylparaben solution dissolved in methanol:water = 1:1

[0068] HPLC conditions for latanoprost ·Mobile phase composition: CH3CN:H2O:HClO4:NaClO4= 625:375:1:5(W / W / W / V) Detection wavelength: 260nm ·Injection volume: 50μL Internal standard solution: butylparaben 20 μg / mL

[0069] Fluticasone propionate (Compound 2) Drug solutions: Fluticasone propionate solution: 0.25 mg / mL or 50 μg / mL in acetonitrile Dilution solution: Methanol 1 mL (0.25 mg / mL) or 200 μL (50 μg / mL) Internal standard solution: 100 μL of 20 μg / mL butylparaben solution dissolved in methanol:water = 1:1

[0070] HPLC conditions for fluticasone propionate ·Mobile phase composition: CH3CN:H2O:HClO4:NaClO4=590:410:1:5 Detection wavelength: 240nm ·Injection volume: 50μL Internal standard solution: butylparaben 20 μg / mL

[0071] Hydrocortisone (Compound 3) Drug solution: Hydrocortisone solution: 0.25 mg / mL aqueous solution Dilution solution: 1 mL of water Internal standard solution: 500 μL of 10 μg / mL ethylparaben solution in water

[0072] HPLC conditions for hydrocortisone ·Mobile phase composition: CH3CN:H2O:HClO4:NaClO4=310:690:1:5 Detection wavelength: 254nm ·Injection volume: 20μL Internal standard solution: ethylparaben 10 μg / mL

[0073] Ketotifen fumarate (Compound 4) Drug solution: Ketotifen fumarate solution: 0.5 mg / mL aqueous solution Dilution solution: 1 mL of methanol:water = 1:1 solution Internal standard solution: 50 μL of 2 mg / mL propylparaben solution dissolved in a 1:1 methanol:water solution

[0074] HPLC conditions for ketotifen fumarate ·Mobile phase composition: CH3CN:H2O:HClO4:NaClO4=450:550:1:5 Detection wavelength: 300nm ·Injection volume: 20μL Internal standard solution: propylparaben 2 mg / mL

[0075] Flavin adenine dinucleotide (compound 5) Drug solution: Medical G eye drops (Santen Pharmaceutical Co., Ltd.) 50 μg / mL Dilution solution: 1 mL of water Internal standard solution: 500 μL of 10 μg / mL theophylline solution dissolved in water

[0076] HPLC conditions for flavin adenine dinucleotide ·Mobile phase composition: KH2PO4(1→500):CH3OH=785:215 Detection wavelength: 260nm ·Injection volume: 10μL

[0077] The results are shown in Table 3 below.

[0078] [Table 3]

[0079] result As a result, flavin adenine dinucleotide (compound 5), which has a solubility in water of 100 mg / mL or more, was completely eluted with water and its elution was suppressed with 80% ethanol. Compound 5 did not require the addition of a surfactant. Ketotifen fumarate (compound 4), which has a solubility of 16.1 mg / mL in water, showed high dissolution rates in water, 80% ethanol, and ionic surfactants (cationic surfactants, anionic surfactants). Among nonionic surfactants, polysorbate 80 and polysorbate 20 at 2 mg / mL showed lower dissolution rates. Hydrocortisone (compound 3), which has a solubility in water of 0.58 mg / mL, showed a lower dissolution rate in water than previous compounds, but a higher dissolution rate in systems containing alcohol. Both ionic and nonionic surfactants showed high efficacy. Latanoprost (Compound 1), which has a solubility in water of 50 μg / mL (0.050 mg / mL), showed high dissolution rates in 80% ethanol solution and nonionic surfactant solution. Fluticasone propionate (Compound 2), which has a solubility in water of 0.1 μg / mL (0.0001 mg / mL), showed low dissolution rates even with nonionic surfactants, and only showed high dissolution rates with 80% ethanol and the anionic surfactant sodium lauryl sulfate solution. Therefore, when the solubility in water is 0.1 mg / mL or more, both ionic and nonionic surfactants are effective, but when the solubility is less than 0.1 mg / mL, nonionic surfactants tend to be more effective. However, some compounds, such as fluticasone propionate, exhibit high dissolution rates only in sodium lauryl sulfate solutions, so investigation of individual compounds is necessary. In the case of latanoprost, a drug used to treat glaucoma, high dissolution rates were found to be achieved in nonionic surfactant solutions.

[0080] Test Example 4 (Optimum concentration of nonionic surfactant) (Preliminary Examination) The optimal concentrations of the nonionic surfactants polyoxyethylene hydrogenated castor oil and polysorbate 80 were investigated. The following drug solutions, test solutions, dilution solutions, and internal standard solutions were used, and the experiment was carried out according to the above-mentioned Experimental Method A. Then, HPLC was measured under the HPLC conditions shown below to determine the dissolution rate of the drug (latanoprost). As test solutions, aqueous solutions of polyoxyethylene hydrogenated castor oil or polysorbate 80 at the concentrations shown in Table 4 below were used. As the drug solution, dilution solution, and internal standard solution, the drug solution, dilution solution, and internal standard solution of latanoprost described in Test Example 3 above were used. The HPLC conditions used were the same as those for latanoprost described in Test Example 3 above. The results are shown in Table 4 below.

[0081] [Table 4]

[0082] result Preliminary testing indicated that polyoxyethylene hydrogenated castor oil and polysorbate 80 had optimal concentrations (Table 4).

[0083] (Main test; detailed experiment) Therefore, detailed studies were carried out on both compounds, polyoxyethylene hydrogenated castor oil and polysorbate 80, at concentrations of 0.5 mg / mL to 10 mg / mL. In the same manner as in the above preliminary test, the dissolution rate of the above-mentioned glaucoma treatment drug, latanoprost, was measured. The results are shown in Table 5.

[0084] [Table 5]

[0085] result Regarding the relationship between the concentration of polyoxyethylene hydrogenated castor oil and polysorbate 80 added and the dissolution rate, the results in Table 5 show that the optimal concentrations for both compounds were 2 mg / mL to 10 mg / mL.

[0086] Test Example 6 (Composition of the Invention: Compounds that Improve Dissolution Rate) Composition samples 6-1 to 6-12 were prepared by blending the additives shown in Table 6 below at the respective concentrations with polyoxyethylene hydrogenated castor oil (2 mg / mL), a nonionic surfactant, and compared with sample 6-13, which contained polyoxyethylene hydrogenated castor oil (2 mg / mL) alone, as a control. The following drug solutions, test solutions, dilution solutions, and internal standard solutions were used, and the experiment was carried out according to the above-mentioned Experimental Method A. Then, HPLC was measured under the HPLC conditions shown below to determine the dissolution rate of the drug (latanoprost). As test solutions, composition samples 6-1 to 6-13 shown in Table 6 below were used. As the drug solution, dilution solution, and internal standard solution, the drug solution, dilution solution, and internal standard solution of latanoprost described in Test Example 3 above were used. The HPLC conditions used were the same as those for latanoprost described in Test Example 3 above.

[0087] [Table 6]

[0088] result As a result, composition samples 6-1 to 6-5 and 6-8 to 6-12, which are eyelid wiping compositions of the present disclosure, showed improved dissolution rates of the glaucoma treatment drugs compared to sample 6-13. The dissolution rates of samples 6-6 and 6-7 were comparable to that of sample 6-13, which contained no additives. These results demonstrate that adding ethanol at a low concentration does not affect the dissolution rate (does not decrease the dissolution rate).

[0089] Test Example 7 (Compounds for improving dissolution rate) Composition samples 7-1 and 7-2 were prepared by further blending the nonionic surfactant polysorbate 80 (2 mg / mL) with the additives shown in Table 7 below at the respective concentrations. As a control, sample 7-3 containing polysorbate (2 mg / mL) alone was used for comparison. The following drug solutions, test solutions, dilution solutions, and internal standard solutions were used, and the experiment was carried out according to the above-mentioned Experimental Method A. Then, HPLC was measured under the HPLC conditions shown below to determine the dissolution rate of the drug (latanoprost). As test solutions, composition samples 7-1 to 7-3 shown in Table 7 below were used. As the drug solution, dilution solution, and internal standard solution, the drug solution, dilution solution, and internal standard solution of latanoprost described in Test Example 3 above were used. The HPLC conditions used were the same as those for latanoprost described in Test Example 3 above.

[0090] [Table 7]

[0091] result As a result, composition samples 7-1 and 7-2, which are eyelid wiping compositions of the present disclosure, had improved dissolution rates of the glaucoma treatment drug compared to sample 7-3.

[0092] Test Example 8 (Effects of other glaucoma medications) Latanoprost and a compound other than latanoprost (tafluprost) were tested as a therapeutic drug for glaucoma. Polysorbate 80 (2 mg / mL) was further mixed with the eluent shown in Table 8 below at the respective concentrations to prepare composition samples 8-1 to 8-13. For latanoprost, the following drug solutions, test solutions, dilution solutions, and internal standard solutions were used, and an experiment was conducted according to the above-mentioned Experimental Method A. Then, HPLC was measured under the HPLC conditions shown below to determine the dissolution rate of the drug (latanoprost). As test solutions, composition samples 8-1 to 8-13 shown in Table 8 below were used. As the drug solution, dilution solution, and internal standard solution, the drug solution, dilution solution, and internal standard solution of latanoprost described in Test Example 3 above were used. The HPLC conditions used were the same as those for latanoprost described in Test Example 3 above.

[0093] For tafluprost, the following drug solutions, test solutions, dilution solutions, and internal standard solutions were used, and the experiment was carried out according to the above-mentioned Experimental Method A. Then, HPLC was measured under the HPLC conditions shown below to determine the dissolution rate of the drug (tafluprost). As test solutions, composition samples 8-1 to 8-13 shown in Table 8 below were used.

[0094] Tafluprost Drug solution: Tafluprost solution: A solution prepared from 15 μg / mL of reagent tafluprost (MedChemExpress) diluted with a 1:9 mixture of acetonitrile (CH3CN):water (H2O). Dilution solution: 50 μL of methanol Internal standard solution: 100 μL of 20 μg / mL butylparaben solution dissolved in methanol:water = 1:1

[0095] HPLC conditions for tafluprost ·Mobile phase composition: CH3CN:H2O:HClO4:NaClO4= 625:375:1:5(W / W / W / V) Detection wavelength: 260nm ·Injection volume: 50μL Internal standard solution: butylparaben 20 μg / mL

[0096] [Table 8]

[0097] result As a result, composition samples 8-4 to 8-7 and 8-10 to 8-12, which are eyelid wiping compositions of the present disclosure, showed a dissolution rate of latanoprost exceeding 70.6%. Composition samples 8-4 to 8-7 and 8-10 to 8-12 also showed a similar dissolution rate for tafluprost. Note that when the nonionic surfactant in the dissolution solution was at the same concentration, latanoprost was more easily dissolved than tafluprost.

[0098] As described above, the eyelid wiping composition of the present disclosure can dissolve and remove a glaucoma treatment drug, thereby demonstrating the possibility of reducing the side effects of the glaucoma treatment drug.

Claims

1. A composition for wiping the eyelid containing a nonionic surfactant, Used to wipe away glaucoma medications, A composition for wiping the eyelid, wherein the therapeutic drug for glaucoma is a prostaglandin derivative.

2. The eyelid wiping composition according to claim 1, which is used to dissolve and remove a glaucoma treatment drug.

3. The eyelid wiping composition according to claim 1, wherein the eyelid wiping composition does not contain any glaucoma treatment drug.

4. The eyelid wiping composition according to claim 1 , wherein the nonionic surfactant comprises an ester-type nonionic surfactant.

5. 2. The eyelid wiping composition according to claim 1, wherein the nonionic surfactant contains at least one compound selected from the group consisting of polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan fatty acid esters (polysorbates), and sucrose fatty acid esters.

6. A composition for wiping the eyelids as described in claim 1, wherein the prostaglandin derivative is a prostaglandin F2α derivative or a prostamide derivative.

7. The composition for wiping the eyelids as described in claim 1, wherein the prostaglandin derivative is latanoprost, tafluprost, or travoprost.

8. The eyelid wiping composition according to claim 1, further comprising cyclodextrin.

9. An eyelid wiping device comprising a wiping device impregnated with the eyelid wiping composition according to any one of claims 1 to 8.

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