CN114786650A - Pharmaceutical composition for soft contact lens - Google Patents
Pharmaceutical composition for soft contact lens Download PDFInfo
- Publication number
- CN114786650A CN114786650A CN202080082048.5A CN202080082048A CN114786650A CN 114786650 A CN114786650 A CN 114786650A CN 202080082048 A CN202080082048 A CN 202080082048A CN 114786650 A CN114786650 A CN 114786650A
- Authority
- CN
- China
- Prior art keywords
- soft contact
- pharmaceutical composition
- contact lens
- less
- contact lenses
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 127
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 55
- 229910001510 metal chloride Inorganic materials 0.000 claims abstract description 43
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical group [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 42
- -1 polyoxyethylene Polymers 0.000 claims description 40
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 34
- 239000008103 glucose Substances 0.000 claims description 33
- 239000000872 buffer Substances 0.000 claims description 26
- 239000011780 sodium chloride Substances 0.000 claims description 21
- 150000001413 amino acids Chemical class 0.000 claims description 20
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 16
- 239000004359 castor oil Substances 0.000 claims description 15
- 235000019438 castor oil Nutrition 0.000 claims description 15
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims description 15
- 239000002736 nonionic surfactant Substances 0.000 claims description 14
- 239000002562 thickening agent Substances 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 11
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 10
- 239000003795 chemical substances by application Substances 0.000 claims description 9
- 239000001103 potassium chloride Substances 0.000 claims description 5
- 235000011164 potassium chloride Nutrition 0.000 claims description 5
- 229910001514 alkali metal chloride Inorganic materials 0.000 claims description 3
- 238000001179 sorption measurement Methods 0.000 abstract description 56
- 239000000243 solution Substances 0.000 description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
- 238000012360 testing method Methods 0.000 description 28
- 239000007788 liquid Substances 0.000 description 21
- 235000001014 amino acid Nutrition 0.000 description 19
- 238000002360 preparation method Methods 0.000 description 18
- 239000000203 mixture Substances 0.000 description 17
- 230000000694 effects Effects 0.000 description 16
- 239000003889 eye drop Substances 0.000 description 16
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
- 229930003658 monoterpene Natural products 0.000 description 12
- 150000002773 monoterpene derivatives Chemical class 0.000 description 12
- 235000002577 monoterpenes Nutrition 0.000 description 12
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- 230000002401 inhibitory effect Effects 0.000 description 11
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- 239000002738 chelating agent Substances 0.000 description 10
- 230000005764 inhibitory process Effects 0.000 description 10
- 238000000034 method Methods 0.000 description 10
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- 229910021538 borax Inorganic materials 0.000 description 9
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 9
- 239000000975 dye Substances 0.000 description 9
- 239000004328 sodium tetraborate Substances 0.000 description 9
- 235000010339 sodium tetraborate Nutrition 0.000 description 9
- 230000000052 comparative effect Effects 0.000 description 8
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- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 7
- WOBHKFSMXKNTIM-UHFFFAOYSA-N Hydroxyethyl methacrylate Chemical compound CC(=C)C(=O)OCCO WOBHKFSMXKNTIM-UHFFFAOYSA-N 0.000 description 7
- 239000002202 Polyethylene glycol Substances 0.000 description 7
- 239000012530 fluid Substances 0.000 description 7
- 238000007654 immersion Methods 0.000 description 7
- 229920001223 polyethylene glycol Polymers 0.000 description 7
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 6
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- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
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- 239000012086 standard solution Substances 0.000 description 6
- 230000001954 sterilising effect Effects 0.000 description 6
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- 229960003080 taurine Drugs 0.000 description 5
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- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
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- 229920001400 block copolymer Polymers 0.000 description 4
- 239000001110 calcium chloride Substances 0.000 description 4
- 229910001628 calcium chloride Inorganic materials 0.000 description 4
- 239000003086 colorant Substances 0.000 description 4
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- 238000009472 formulation Methods 0.000 description 4
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- REPVLJRCJUVQFA-UHFFFAOYSA-N (-)-isopinocampheol Natural products C1C(O)C(C)C2C(C)(C)C1C2 REPVLJRCJUVQFA-UHFFFAOYSA-N 0.000 description 3
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- 241000894006 Bacteria Species 0.000 description 3
- 241000723346 Cinnamomum camphora Species 0.000 description 3
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 3
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 3
- 235000011054 acetic acid Nutrition 0.000 description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
- 235000003704 aspartic acid Nutrition 0.000 description 3
- 229960000686 benzalkonium chloride Drugs 0.000 description 3
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 3
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 3
- CKDOCTFBFTVPSN-UHFFFAOYSA-N borneol Natural products C1CC2(C)C(C)CC1C2(C)C CKDOCTFBFTVPSN-UHFFFAOYSA-N 0.000 description 3
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- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 3
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 3
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical group OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 3
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- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
- ABSTXSZPGHDTAF-UHFFFAOYSA-N 4-amino-pentanoic acid Chemical compound CC(N)CCC(O)=O ABSTXSZPGHDTAF-UHFFFAOYSA-N 0.000 description 2
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- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- OXJGJKIURHREKH-UHFFFAOYSA-O CC(=C)C(=O)OCCP(=O)=C(O)C[N+](C)(C)C Chemical compound CC(=C)C(=O)OCCP(=O)=C(O)C[N+](C)(C)C OXJGJKIURHREKH-UHFFFAOYSA-O 0.000 description 2
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/04—Artificial tears; Irrigation solutions
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- Health & Medical Sciences (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Ophthalmology & Optometry (AREA)
- Inorganic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
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- Biochemistry (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The purpose of the present invention is to provide a pharmaceutical composition for soft contact lenses, which inhibits the adsorption of alkyldiaminoethylglycine to soft contact lenses. The pharmaceutical composition for soft contact lenses according to the present invention contains an alkyldiaminoethylglycine hydrochloride in an amount of 0.001 to 0.008 w/v% and a metal chloride.
Description
Technical Field
The present invention relates to a pharmaceutical composition for soft contact lenses which inhibits adsorption of alkyldiaminoethylglycine to soft contact lenses.
Background
In order to reduce the unpleasant feeling when wearing a soft contact lens or a hard contact lens, various pharmaceutical compositions for soft contact lenses having a composition similar to tear fluid have been studied. Lacrimal fluid secreted from the main lacrimal gland contains 4 or more substances secreted from the accessory lacrimal gland, and contains Na, K, Ca, Cl, etc. as inorganic components and glucose, ascorbic acid, citric acid, urea, ammonia, amino acids, proteins, etc. as organic components. Although there are individual differences, the concentration of glucose contained in tears is about 0.001 to 0.01 w/v%. However, in an aqueous liquid preparation for ophthalmic use, glucose is sometimes compounded as a nutritional ingredient at a higher concentration than tear fluid. For example, the ophthalmic aqueous liquid preparations disclosed in patent documents 1 to 4 have a glucose concentration of about 0.1 w/v%. On the other hand, there are bacteria that metabolize glucose to produce pyruvic acid and thereby obtain energy, and glucose may promote the growth of such bacteria. Therefore, particularly for ophthalmic aqueous liquid preparations with a reduced content of a storage agent and a preservative, glucose is generally mixed at a lower concentration than that of lacrimal fluid.
Even if the concentration of glucose is reduced, a preservative is added to the pharmaceutical composition for storage or the like. However, since the eye drops are directly administered to the eyes, preservatives sometimes show side effects. For example, non-patent documents 1 to 5 describe that preservatives such as benzalkonium chloride damage cells, irritate the skin, and the like, and show that povidone-iodine toxicity is the lowest and alkyldiaminoethylglycine toxicity is moderate. Patent documents 1 to 4 also disclose ophthalmic compositions containing alkyldiaminoethylglycine hydrochloride.
Documents of the prior art
Patent document
Patent document 1: japanese laid-open patent application No. 2001-302518
Patent document 2: japanese patent laid-open publication No. 2001-302545
Patent document 3: japanese patent laid-open publication No. 2009-46480
Patent document 4: japanese patent laid-open publication No. 2005-336153
Non-patent document
Non-patent document 1: gaoqianfu et al, in the department of ophthalmology, japan, 58: no. 10, pp.945 to 950(1987)
Non-patent document 2: tji Mingliang et al, hooked sensation on a daily surface, Vol.11, No.3, pp.207-220 (1996)
Non-patent document 3: あ insert さい, Vol.12, No.4, pp.67-73 (2003)
Non-patent document 4: zhongshikazai, second-class, Japanese medicine , Vol.40, No.12, pp.1559-1562 (2004)
Non-patent document 5: baishizheng, am of academic society of japan, Vol.99, No.8, pp.166-172 (2010)
Disclosure of Invention
Problems to be solved by the invention
The purpose of the present invention is to provide a pharmaceutical composition for soft contact lenses, which inhibits the adsorption of alkyldiaminoethylglycine to soft contact lenses.
Means for solving the problems
The present inventors have conducted intensive studies to solve the above problems. As a result, they have found that when alkyldiaminoethylglycine hydrochloride is added to a pharmaceutical composition for a soft contact lens at a low concentration, alkyldiaminoethylglycine in particular tends to adsorb to the soft contact lens, but such adsorption can be suppressed by further adding a metal chloride, and have completed the present invention.
One embodiment of the present invention is shown below.
[1] A pharmaceutical composition for soft contact lenses, which contains an alkyldiaminoethylglycine hydrochloride in an amount of 0.001 to 0.008 w/v% and a metal chloride.
[2] The pharmaceutical composition for a soft contact lens according to the above [1], which comprises 0.001 to 0.0075 w/v% of alkyldiaminoethylglycine hydrochloride.
[3] The pharmaceutical composition for a soft contact lens according to the above [1], which comprises 0.001 to 0.005 w/v% of alkyldiaminoethylglycine hydrochloride.
[4] The pharmaceutical composition for a soft contact lens according to any one of the above [1] to [3], wherein the metal chloride is at least 1 salt selected from the group consisting of alkali metal chlorides and group IIA metal chlorides.
[5] The pharmaceutical composition for a soft contact lens according to any one of the above [1] to [3], wherein the metal chloride is sodium chloride and/or potassium chloride.
[6] The pharmaceutical composition for a soft contact lens according to any one of the above [1] to [5], which contains a metal chloride in an amount of 0.05 to 5.0 w/v%.
[7] The pharmaceutical composition for a soft contact lens according to any one of the above [1] to [5], which contains a metal chloride in an amount of 0.1 to 2.0 w/v%.
[8] The pharmaceutical composition for a soft contact lens according to any one of the above [1] to [7], which further contains glucose.
[9] The pharmaceutical composition for a soft contact lens according to the above [8], which comprises 0.001 to 0.01 w/v% of glucose.
[10] The pharmaceutical composition for a soft contact lens according to the above [8], which comprises 0.002 to 0.008 w/v% of glucose.
[11] The pharmaceutical composition for a soft contact lens according to any one of the above [1] to [10], which comprises 0.001 w/v% or more and 0.005 w/v% or less of alkyldiaminoethylglycine hydrochloride and 0.5 w/v% or more and 1 w/v% or less of a metal chloride.
[12] The pharmaceutical composition for a soft contact lens according to any one of the above [1] to [11], which comprises:
0.001 to 0.005 w/v% of alkyldiaminoethylglycine hydrochloride,
0.5 to 1 w/v% of a metal chloride, and
0.002 w/v% or more and 0.008 w/v% or less of glucose.
[13] The pharmaceutical composition for a soft contact lens according to any one of the above [1] to [12], which further comprises a nonionic surfactant.
[14] The pharmaceutical composition for soft contact lenses according to the above [13], wherein the nonionic surfactant is at least 1 nonionic surfactant selected from the group consisting of polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan mono-long-chain fatty acid ester, mono-long-chain fatty acid polyethylene glycol ester, and polyoxyethylene polyoxypropylene block copolymer.
[15] The pharmaceutical composition for a soft contact lens according to the above [14], wherein the polyoxyethylene hydrogenated castor oil is polyoxyethylene hydrogenated castor oil 60.
[16] The pharmaceutical composition for a soft contact lens according to any one of [13] to [15], wherein the concentration of the nonionic surfactant is 0.001 w/v% or more and 0.5 w/v% or less.
[17] The pharmaceutical composition for a soft contact lens according to any one of the above [13] to [15], wherein the concentration of the nonionic surfactant is 0.001 w/v% or more and 0.1 w/v% or less.
[18] The pharmaceutical composition for a soft contact lens according to any one of the above [13] to [15], wherein the concentration of the nonionic surfactant is 0.005 w/v% or more and 0.05 w/v% or less.
[19] The pharmaceutical composition for a soft contact lens according to any one of the above [1] to [18], which further comprises a buffer agent.
[20] The pharmaceutical composition for soft contact lenses according to the above [19], wherein the buffer is at least 1 buffer selected from the group consisting of a boric acid buffer, a phosphoric acid buffer, a carbonic acid buffer, a citric acid buffer, an acetic acid buffer, a HEPES buffer, and a MOPS buffer.
[21] The pharmaceutical composition for soft contact lenses according to the above [19], wherein the buffer is boric acid and/or borax.
[22] The pharmaceutical composition for a soft contact lens according to any one of the above [19] to [21], which comprises a buffer agent in an amount of 0.05 to 5.0 w/v%.
[23] The pharmaceutical composition for a soft contact lens according to any one of the above [19] to [21], which comprises a buffer agent in an amount of 0.1 to 1.0 w/v%.
[24] The pharmaceutical composition for a soft contact lens according to any one of the above [1] to [23], further comprising a thickener.
[25] The pharmaceutical composition for a soft contact lens according to the above [24], wherein the thickening agent is hydroxypropylmethylcellulose.
[26] The pharmaceutical composition for a soft contact lens according to the above [24] or [25], which comprises 0.01 w/v% or more and 1 w/v% or less of a thickening agent.
[27] The pharmaceutical composition for a soft contact lens according to [24] or [25], which comprises 0.05 to 0.5 w/v% of the thickening agent.
[28] The pharmaceutical composition for a soft contact lens according to any one of the above [1] to [27], further comprising an amino acid.
[29] The pharmaceutical composition for soft contact lenses according to the above [28], wherein the amino acid is at least 1 amino acid selected from the group consisting of taurine, glutamic acid, aspartic acid, glycine, alanine, arginine, lysine, γ -aminobutyric acid, γ -aminopentanoic acid, and salts thereof.
[30] The pharmaceutical composition for soft contact lenses according to the above [28], wherein the amino acid is taurine.
[31] The pharmaceutical composition for a soft contact lens according to any one of the above [28] to [30], which contains 0.01 to 1.0 w/v% of an amino acid.
[32] The pharmaceutical composition for a soft contact lens according to any one of the above [28] to [30], which contains 0.05 to 0.5 w/v% of the amino acid.
[33] The pharmaceutical composition for a soft contact lens according to any one of the above [1] to [31], which comprises:
0.001 to 0.005 w/v% of alkyldiaminoethylglycine hydrochloride,
0.1 to 2.0 w/v% of a metal chloride,
0.002 to 0.008 w/v% of glucose,
0.005 to 0.05 w/v% of polyoxyethylene hydrogenated castor oil,
A buffer agent of 0.1 to 2.0 w/v%,
0.05 w/v% or more and 0.5 w/v% or less of a thickener, and
0.05 w/v% or more and 0.5 w/v% or less of an amino acid.
[34] The pharmaceutical composition for a soft contact lens according to any one of the above [1] to [33], which further comprises a pH adjuster.
[35] The pharmaceutical composition for a soft contact lens according to any one of the above [1] to [34], wherein the pH is 5.0 or more and 8.5 or less.
[36] The pharmaceutical composition for a soft contact lens according to any one of the above [1] to [34], wherein the pH is 5.5 or more and 8.0 or less.
[37] The pharmaceutical composition for a soft contact lens according to any one of the above [1] to [34], wherein the pH is from 6.5 to 7.5.
[38] The pharmaceutical composition for a soft contact lens according to any one of the above [1] to [37], further comprising a monoterpene.
[39] The pharmaceutical composition for a soft contact lens according to the above [38], wherein the monoterpene is at least 1 monoterpene selected from the group consisting of menthol, camphor and borneol.
[40] The pharmaceutical composition for soft contact lenses according to the above [38], wherein the monoterpene is l-menthol.
[41] The pharmaceutical composition for a soft contact lens according to any one of [38] to [40], which contains 0.0005 to 0.1 w/v% of a monoterpene.
[42] The pharmaceutical composition for a soft contact lens according to any one of [38] to [40], which contains 0.001 w/v% or more and 0.035 w/v% or less of a monoterpene.
[43] The pharmaceutical composition for a soft contact lens according to any one of the above [1] to [42], which further comprises a chelating agent.
[44] The pharmaceutical composition for a soft contact lens according to the above [43], wherein the chelating agent is ethylenediaminetetraacetic acid or a salt thereof.
[45] The pharmaceutical composition for a soft contact lens according to [43] or [44], which comprises a chelating agent in an amount of 0.001 to 0.1 w/v%.
[46] The pharmaceutical composition for a soft contact lens according to [43] or [44], which comprises 0.005 to 0.05 w/v% of a chelating agent.
[47] The pharmaceutical composition for a soft contact lens according to any one of the above [1] to [46], which comprises:
0.001 to 0.005 w/v% of alkyldiaminoethylglycine hydrochloride,
0.5 to 1.0 w/v% of a metal chloride,
0.002 to 0.008 w/v% of glucose,
0.005 to 0.05 w/v% of a nonionic surfactant,
A buffer agent of 0.1 to 2.0 w/v%,
0.05 to 0.5 w/v% of a thickener,
0.05 to 0.5 w/v% of an amino acid,
Monoterpene of 0.001 w/v% or more and 0.035 w/v% or less, and
0.005 w/v% or more and 0.05 w/v% or less of a chelating agent.
[48] The pharmaceutical composition for a soft contact lens according to any one of the above [1] to [46], which comprises:
0.001 to 0.005 w/v% of alkyldiaminoethylglycine hydrochloride,
0.5 to 1.0 w/v% of a metal chloride,
0.002 to 0.008 w/v% of glucose,
0.005 to 0.05 w/v% of a nonionic surfactant,
A buffer agent of 0.1 to 2.0 w/v%,
0.05 to 0.5 w/v% of a thickener,
0.05 to 0.5 w/v% of an amino acid,
More than 0.001 w/v% and less than 0.035 w/v% of monoterpene, and
0.005 w/v% or more and 0.05 w/v% or less of a chelating agent,
and the pH of the pharmaceutical composition for soft contact lenses is 6.5 or more and 7.5 or less.
[49] The pharmaceutical composition for a soft contact lens according to any one of the above [1] to [48], which is used for ophthalmology.
[50] The pharmaceutical composition for a soft contact lens according to any one of the above [1] to [48], which is an aqueous liquid preparation.
[51] The pharmaceutical composition for a soft contact lens according to any one of the above [1] to [48], which is an eye drop.
[52] Use of a metal chloride for inhibiting adsorption of alkyldiaminoethylglycine to a soft contact lens in a pharmaceutical composition comprising 0.001 to 0.008 w/v% of alkyldiaminoethylglycine hydrochloride.
[53] Use of a metal chloride for producing a pharmaceutical composition for inhibiting adsorption of alkyldiaminoethylglycine to a soft contact lens in a pharmaceutical composition containing 0.001 to 0.008 w/v% of alkyldiaminoethylglycine hydrochloride.
[54] A method for inhibiting the adsorption of alkyldiaminoethylglycine to a soft contact lens,
the content of alkyldiaminoethylglycine hydrochloride in the pharmaceutical composition for soft contact lenses is 0.001 w/v% or more and 0.008 w/v% or less,
a metal chloride is compounded in the medicinal composition for the soft contact lens.
[55] According to the method of [54], glucose is further blended in the pharmaceutical composition for soft contact lenses.
The above-mentioned items [1] to [51] can be applied to the above-mentioned use and method.
ADVANTAGEOUS EFFECTS OF INVENTION
The pharmaceutical composition for soft contact lenses according to the present invention contains alkyldiaminoethylglycine hydrochloride, but adsorption of alkyldiaminoethylglycine to soft contact lenses is suppressed.
Detailed Description
As described above, various pharmaceutical compositions have been developed, and for the purpose of storage stability, an antiseptic is added to an eye drop. Among preservatives used in pharmaceutical compositions, alkyldiaminoethylglycine hydrochloride is said to have lower cytotoxicity than benzalkonium chloride and the like.
However, the present inventors have found that alkyldiaminoethylglycine has a tendency to adsorb to soft contact lenses if lower concentrations of alkyldiaminoethylglycine hydrochloride are compounded in pharmaceutical compositions for soft contact lenses. Therefore, the components inhibiting such adsorption were investigated, and as a result, it was found that the metal chloride is effective.
The pharmaceutical composition for soft contact lenses according to the present invention contains an alkyldiaminoethylglycine hydrochloride in an amount of 0.001 to 0.008 w/v% and a metal chloride.
Hereinafter, alkyldiaminoethylglycine may be abbreviated as "ADG" and a soft contact lens may be abbreviated as "SCL".
"alkyldiaminoethylglycine hydrochloride" is a compound having the following chemical structure, and has been used mainly as a preservative component.
R-NH-(CH2)2-NH-(CH2)2-NH-CH2-CO2H·HCl
[ in the formula, R represents C8H17~C16H33Alkyl of (2), mainly C12H25And C14H29。]
In order to provide a pharmaceutical composition for a soft contact lens having low cytotoxicity and the like, the present inventors set the blending amount of alkyldiaminoethylglycine hydrochloride in the pharmaceutical composition for a soft contact lens to 0.001 w/v% or more and 0.008 w/v% or less to be low. If the concentration is 0.001 w/v% or more, the preservative effect is more surely exhibited. On the other hand, if the concentration is 0.008 w/v% or less, cytotoxicity and the like are more surely suppressed, and the present inventors have found through experiments that the lower the concentration of alkyldiaminoethylglycine hydrochloride, the higher the adsorption rate of alkyldiaminoethylglycine to a soft contact lens. The concentration is preferably 0.002 w/v% or more, more preferably 0.005 w/v% or less, and still more preferably 0.003 w/v% or less.
By "metal chloride" is meant a metal cation and chloride ion (Cl)-) The salt formed is mixed as a component for inhibiting the adsorption of alkyldiaminoethylglycine to the soft contact lens in the present invention. Examples of the metal chloride include alkali metal chlorides such as sodium chloride and potassium chloride; the group IIA metal chloride such as calcium chloride or magnesium chloride is preferably an alkaline earth metal chloride such as calcium chloride, and is preferably a water-soluble metal chloride. "Water-soluble" means that the amount of water required for dissolving the test substance in a 30 minute or less is less than 10mL when the test substance is made into a fine powder that can pass through a No. 100 (mesh opening: 150 μm) sieve, 1g of the fine powder is added to water, and the mixture is vigorously shaken every 5 minutes at 20 ℃ for 30 seconds.
The concentration of the metal chloride in the pharmaceutical composition for soft contact lenses may be appropriately adjusted within a range in which the above-described adsorption effect is effectively exhibited, but may be, for example, 0.05 w/v% or more and 5.0 w/v% or less. When the concentration is within this range, the adsorption effect is more reliably exhibited. The concentration is preferably 0.1 w/v% or more, more preferably 0.5 w/v% or more, and is preferably 2.0 w/v% or less, more preferably 1.0 w/v% or less.
The metal chloride may be used alone in 1 kind, or may be used in combination of 2 or more kinds. When 2 or more metal chlorides are used, the above concentration is a total concentration.
"glucose" is of formula C6H12O6One of the aldohexoses, also called glucose (glucose), is D-glucose present in nature, and in animals having a respiratory system, a large amount of ATP is produced by conjugation with an electron transport system, and 0.001 w/v% or more and 0.01 w/v% or less are present in tears.
In the present invention, it is preferable to add glucose in order to assist the effect of suppressing adsorption of alkyldiaminoethylglycine to the soft contact lens by the metal chloride. Preferably, the pharmaceutical composition for soft contact lenses according to the present invention contains 0.001 to 0.01 w/v% of glucose. If the ratio is 0.001 w/v% or more, the adsorption-inhibiting effect by the metal chloride can be more surely protected, and if the ratio is 0.01 w/v% or less, the stability of the eye drop can be more surely ensured. The proportion is more preferably 0.002 w/v% or more, still more preferably 0.004 w/v% or more, and further more preferably 0.008 w/v% or less, and still more preferably 0.006 w/v% or less.
The "nonionic surfactant" is a surfactant that does not dissociate into ions even when dissolved in water, and generally, a polyoxyethylene chain or a hydroxyl group functions as a hydrophilic group, and a long-chain alkyl group becomes a hydrophobic group. The nonionic surfactant contributes to the stability of the eye drop. Examples of the nonionic surfactant include 1 or more nonionic surfactants selected from the group consisting of polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan mono-long chain fatty acid ester, mono-long chain fatty acid polyethylene glycol ester, and polyoxyethylene polyoxypropylene block copolymer.
The polyoxyethylene hydrogenated castor oil is a compound obtained by etherifying hydrogenated castor oil with a polyoxyethylene chain. The number of addition mols of ethylene oxide of the polyoxyethylene chain in the polyoxyethylene hydrogenated castor oil may be, for example, 5 to 100. The number is preferably 10 or more, or 20 or more, more preferably 30 or more, still more preferably 40 or more, and furthermore preferably 90 or less, more preferably 80 or less, still more preferably 70 or less. As the polyoxyethylene hydrogenated castor oil, polyoxyethylene hydrogenated castor oil 5, polyoxyethylene hydrogenated castor oil 10, polyoxyethylene hydrogenated castor oil 60, and the like can be used, and polyoxyethylene hydrogenated castor oil 60 can be suitably used. In addition, the number after polyoxyethylene hydrogenated castor oil indicates the number of addition moles of ethylene oxide.
Polyoxyethylene sorbitan single long-chain fatty acid esters are also called polysorbates (polysorbates), and are polyoxyethylene ethers of sorbitan fatty acid esters obtained by subjecting sorbitol and a long-chain fatty acid to a heating reaction under an alkali catalyst to generate a sorbitan long-chain fatty acid ester, and subjecting ethylene oxide and the sorbitan long-chain fatty acid ester to a condensation reaction. Usually, a total of about 18 to 22 molecules of ethylene oxide are bound to 1 molecule. The number of carbon atoms of the long-chain fatty acid is generally about 10 to 20, and examples of the long-chain fatty acid include lauric acid, palmitic acid, stearic acid, and oleic acid. As polyoxyethylene sorbitan mono-long chain fatty acid esters, for example, polysorbate 20, polysorbate 60, polysorbate 65, and polysorbate 80 may be used, and polysorbate 80 is preferable.
The polyethylene glycol ester of a single long-chain fatty acid is an ester of a long-chain fatty acid and polyethylene glycol, and the long-chain fatty acid includes stearic acid, and the polymerization degree of polyethylene glycol is about 10 to 60. As the polyethylene glycol monolong chain fatty acid ester, stearic acid-40-Polyoxyl ester (Polyoxyl 40Stearate) is preferable.
The polyoxyethylene polyoxypropylene block copolymer is a copolymer of propylene oxide and ethylene oxide. Examples of the polyoxyethylene polyoxypropylene block copolymer include polyoxyethylene (160) polyoxypropylene (30) diol (poloxamer 188), polyoxyethylene (196) polyoxypropylene (67) diol (poloxamer 407), and poloxamer 235.
The concentration of the nonionic surfactant in the pharmaceutical composition may be adjusted as appropriate, and may be, for example, 0.001 to 0.5 w/v%. When the concentration is within this range, the stabilizing effect of the pharmaceutical composition is more reliably exerted. The concentration is preferably 0.005 w/v% or more, more preferably 0.008 w/v% or more, and further preferably 0.1 w/v% or less, more preferably 0.05 w/v% or less, and still more preferably 0.02 w/v% or less.
The "buffer" is a compound mainly used for alleviating a change in pH due to an external substance, and includes, for example, 1 or more buffers selected from a boric acid buffer, a phosphoric acid buffer, a carbonic acid buffer, a citric acid buffer, an acetic acid buffer, a HEPES buffer, and a MOPS buffer. The buffer is preferably a boric acid buffer, more preferably boric acid and/or borax. Boric acid and borax may also be used as preservatives, and also exhibit a disinfecting effect on the conjunctival sac.
The concentration of the buffer in the pharmaceutical composition for soft contact lenses may be adjusted as appropriate, and may be, for example, 0.05 w/v% or more and 5.0 w/v% or less. When the concentration is within this range, the buffering action of the buffer is more reliably exhibited. The concentration is preferably 0.1 w/v% or more, more preferably 0.5 w/v% or more, and further preferably 2.0 w/v% or less, more preferably 1.0 w/v% or less.
The "thickener" is a component that increases the viscosity of the pharmaceutical composition for soft contact lenses and contributes to suppression of rapid evaporation, improvement of liquid-cutting property, suppression of variation in the amount of dripping, improvement of feeling in use, and the like of the pharmaceutical composition for soft contact lenses. In the present invention, glucose is mixed as a component for assisting the effect of suppressing adsorption of alkyldiaminoethylglycine to the soft contact lens by the metal chloride, and therefore, glucose is excluded from the category of the thickener in the present invention for convenience.
The viscosity of the pharmaceutical composition for soft contact lenses according to the present invention may be appropriately adjusted, and may be, for example, 1.0mPa · s or more and 200mPa · s or less. The viscosity is preferably 50mPa · s or less or 30mPa · s or less, more preferably 10mPa · s or less, and even more preferably 3.0mPa · s or less.
Examples of the thickener include hydroxypropyl methylcellulose, carboxyvinyl polymer, hydroxyethyl cellulose, methylcellulose, alginic acid, polyvinyl alcohol, and polyvinyl pyrrolidone, and hydroxypropyl methylcellulose is preferable.
The concentration of the thickener in the pharmaceutical composition for a soft contact lens may be adjusted as appropriate, and may be, for example, 0.01 w/v% or more and 1.0 w/v% or less. When the concentration is within this range, the above-mentioned effect of the thickener is more surely exhibited. The concentration is preferably 0.05 w/v% or more, more preferably 0.08 w/v% or more, and further preferably 0.5 w/v% or less, more preferably 0.2 w/v% or less.
The "amino acid" is a compound having 1 intramolecular carboxyl group or sulfo group (-SO)3H) And the like, and is not limited to 20 kinds of protein-constituting amino acids. Amino acids are mainly nutritional components for eyes, and help to relieve eye fatigue. Examples of the amino acid include 1 or more amino acids selected from taurine, glutamic acid, aspartic acid, glycine, alanine, arginine, lysine, γ -aminobutyric acid, γ -aminopentanoic acid, and salts thereof. Examples of the amino acid salt include alkali metal salts such as sodium salt and potassium salt. Taurine is preferred as the amino acid. Taurine is considered to exhibit a metabolism promoting effect in addition to being a nutrient component.
The concentration of the amino acid in the pharmaceutical composition for soft contact lenses may be adjusted as appropriate, and may be, for example, 0.01 w/v% or more and 1.0 w/v% or less. When the concentration is within this range, the action of each amino acid is more reliably exhibited. The concentration is preferably 0.05 w/v% or more, more preferably 0.08 w/v% or more, still more preferably 0.1 w/v% or more, and furthermore preferably 0.5 w/v% or less, more preferably 0.2 w/v% or less.
The pH of the pharmaceutical composition for soft contact lenses according to the present invention is adjusted to a range applicable to living bodies, particularly to the eyes. The pH may be, for example, 5.0 or more and 8.5 or less, preferably 5.5 or more, more preferably 6.0 or more, still more preferably 6.5 or more, and further preferably 8.0 or less, more preferably 7.5 or less. In the present invention, it is proved from experiments that: the adsorption inhibiting effect of alkyldiaminoethylglycine on a soft contact lens by a metal chloride is particularly remarkable in a range of pH 6.5 or more and 7.5 or less. The pH of the pharmaceutical composition for soft contact lenses can be adjusted by the buffer or by a pH adjuster.
The pH adjuster is not particularly limited as long as it can be applied to living bodies, particularly eyes, and examples thereof include inorganic acids such as hydrochloric acid and boric acid; organic acids such as acetic acid, glutamic acid, and aspartic acid; inorganic bases such as sodium hydroxide, sodium carbonate and sodium hydrogen carbonate; organic bases such as triethanolamine and monoethanolamine. The type and amount of the pH adjuster may be determined in accordance with the pH to be adjusted in the pharmaceutical composition for soft contact lenses.
A "monoterpene" is formed by 2 isoprene units and has C10H16The compound of the formula (1) mainly uses a monocyclic monoterpene which exhibits a cooling effect in the present invention. Examples of the monoterpene include 1 or more monoterpenes selected from menthol, camphor, and borneol. As menthol, both l-menthol and dl-menthol can be used, but l-menthol is preferred. Camphor and borneol are preferable, although d-isomer and dl-isomer can be used.
The concentration of the monoterpene in the pharmaceutical composition for soft contact lenses may be adjusted as appropriate, and may be, for example, 0.0005 to 0.1 w/v%. When the concentration is within this range, a moderate cooling sensation can be more reliably obtained. The concentration is preferably 0.001 w/v% or more, more preferably 0.0015 w/v% or more, and further preferably 0.02 w/v% or less, more preferably 0.01 w/v% or less.
The "chelating agent" blocks metal ions such as calcium ions to suppress the formation of insoluble metal salts thereof, thereby improving the stability of the eye drops. The chelating agent is not particularly limited as long as it can be applied to living bodies, particularly eyes, and has such an action, and examples thereof include ethylenediaminetetraacetic acid (ethylenediaminetetraacetic acid), ascorbic acid, citric acid, and salts thereof. Examples of the salt of ethylenediaminetetraacetic acid include tetrasodium ethylenediaminetetraacetate and disodium ethylenediaminetetraacetate.
The concentration of the chelating agent in the pharmaceutical composition for a soft contact lens may be adjusted as appropriate, and may be, for example, 0.001 w/v% or more and 0.2 w/v% or less. When the concentration is within this range, the stabilizing effect of the chelating agent can be more reliably obtained. The concentration is preferably 0.002 w/v% or more, more preferably 0.005 w/v% or more, and further preferably 0.2 w/v% or less, more preferably 0.05 w/v% or less, and still more preferably 0.02 w/v% or less.
The pharmaceutical composition for soft contact lenses according to the present invention is not particularly limited as long as the effects of the present invention are not impaired, but a storage agent or a preservative other than alkyldiaminoethyl glycinate may be added. Examples of the storage agent or preservative include benzalkonium chloride, benzalkonium bromide, benzethonium chloride, chlorhexidine hydrochloride, chlorhexidine gluconate, chlorhexidine acetate, chlorobutanol, benzyl alcohol, phenethyl alcohol, sorbic acid or a salt thereof, methyl paraben, ethyl paraben, propyl paraben, dehydroacetic acid or a salt thereof, zinc chloride, porelium chloride, thimerosal, dibutylhydroxytoluene, sodium chlorite, boric acid, borax, and the like. These preservatives and preservatives may be used singly in 1 kind, and in addition, 2 or more kinds may be used in combination.
In addition, the above components can be used respectively only 1 kind, also can be used appropriately in combination with more than 2.
Soft contact lenses are classified into 4 kinds by FDA (united states food and drug administration). I.e., classified as group I: soft contact lenses with water content less than 50% and being non-ionic, group II: soft contact lenses having a water content of 50% or more and being nonionic, group III: soft contact lenses with water content less than 50% and being ionic, group IV: a soft contact lens having a water content of 50% or more and being ionic, wherein the soft contact lens having a mole% of a monomer having an anion out of constituent monomers of a raw material polymer of 1% or more is made ionic, and the soft contact lens having a water content of less than 1% is made nonionic. The soft contact lenses in the present disclosure may be any of the soft contact lenses described above, regardless of the difference in ionic or nonionic, aqueous or non-aqueous properties.
In the present disclosure, examples of the "soft contact lens" include soft contact lenses mainly composed of 2-hydroxyethyl methacrylate (HEMA), EGDMA, SiMAA2, mPDMS1000, CE-PDMS, TRIS, EMA, methacryloyloxyethyl phosphorylcholine, TrisVC, MMA, MA, polyethylene glycol monomethacrylate (PEGMA), Glycerol Methacrylate (GMA), N-Dimethylacrylamide (DMA), Vinyl Alcohol (VA), N-vinylpyrrolidone (NVP or VP), methacrylic acid (MAA), a fluorine-containing methacrylate compound, a silicon-containing methacrylate compound, a silicone hydrogel, a cycloalkyl methacrylate, and the like.
The soft contact lens in the present disclosure may be any of the above-described materials, but preferably includes a soft contact lens containing 2-hydroxyethyl methacrylate (HEMA) as a main component, and more preferably includes a soft contact lens containing 2-hydroxyethyl methacrylate (HEMA) and EGDMA as main components, or a soft contact lens containing HEMA and methacryloyloxyethyl phosphorylcholine as main components.
The type of soft contact lens is not particularly limited, and disposable soft contact lenses, periodically replaceable soft contact lenses, existing soft contact lenses, silicone hydrogel contact lenses, and color contact lenses can be used.
The silicone hydrogel contact lens is made of a silicone hydrogel material.
The colored contact lenses are also called colored contact lenses, and are colored contact lenses for cosmetic purposes such as eye decoration and beauty. For example, a color contact lens is used to make a region of the iris or the cornea look larger than a state in which the contact lens is not worn, and more specifically, to color a region larger than the outer periphery of the iris or the cornea. Such a colored contact lens is sometimes called a circular lens.
As the coloring agent used for coloring a colored contact lens, known coloring agents such as inorganic coloring agents and organic coloring agents can be used. Examples of such a dye include azo dyes, phthalocyanine dyes, diketopyrrolopyrrole dyes, anthraquinone dyes, and triphenylbisThe alkyl dye, the violanthrone dye, the isoindoline dye, the carbazole dye, the quinoline dye, the metal oxide dye, the carbon black, etc., may be used in combination of 1 or 2 or more depending on the color, design, etc., of the color contact lens. In the present disclosure, even substances called pigments and dyes can be used by known means. In addition, both soft contact lenses other than color soft contact lenses and clear contact lenses are sometimes colored in a light color to such an extent that they can be easily visually discriminated when immersed in a solution such as a cleaning solution.
The pharmaceutical composition for soft contact lenses according to the present invention can be produced by a conventional method. For example, the components may be dissolved in water as a solvent. As the water as the solvent, for example, purified water, impurities such as distilled water, purified water, and sterilized water, and clear water having a concentration lower than the detection limit or sufficiently lower than the detection limit, such as bacteria, viruses, and fungi, are used.
The container for containing the pharmaceutical composition for soft contact lenses of the present invention is not particularly limited, and may be made of glass or plastic, as long as it is a container conventionally used as an eye drop container. When the container for containing the pharmaceutical composition for soft contact lenses of the present invention is made of plastic, the material of the plastic container is not particularly limited, and examples thereof include 1 kind of the polyethylene naphthalate, polyarylate, polyethylene terephthalate, polybutylene terephthalate, polypropylene, polyethylene, and polyimide, or a mixture of 2 or more kinds thereof. From the viewpoint of ensuring the stability of the pharmaceutical composition for a soft contact lens more reliably, the material of the member forming the container body, that is, the receiving portion for receiving the pharmaceutical composition for a soft contact lens is preferably polyethylene terephthalate, polypropylene, or polyethylene, and more preferably polyethylene terephthalate.
The inhibition of the adsorption of alkyldiaminoethylglycine to a soft contact lens in the pharmaceutical composition for a soft contact lens according to the present invention is evaluated by the following method: the adsorption rate of alkyldiaminoethylglycine on a soft contact lens contained in the pharmaceutical composition for a soft contact lens impregnated with a soft contact lens is lower than the adsorption rate of alkyldiaminoethylglycine on a soft contact lens impregnated with a liquid having the same composition except that the liquid does not contain a metal chloride. The impregnation of the soft contact lens can be performed, for example, by shaking the liquid impregnated with the soft contact lens at 25 ℃ for 24 hours. The amount of alkyldiaminoethylglycine can be measured, for example, by the absorbance of light of a liquid wavelength obtained by reacting a color former such as eosin Y with alkyldiaminoethylglycine, high performance liquid chromatography, or the like.
The pharmaceutical composition for soft contact lenses according to the present invention assists tears, and is effective in reducing discomfort, dry eyes, eye fatigue, blurred eyes, and the like when wearing soft contact lenses.
The pharmaceutical composition of the present invention can be used in any form for oral administration or external use depending on the purpose. The liquid preparation can be provided in an internal form for medical use, and in an external form for various uses such as ophthalmic use, dental use, otorhinological use, and dermatological use. Ophthalmic use is particularly preferred.
The term "pharmaceutical composition for ophthalmic use" refers to a pharmaceutical composition for ophthalmic use. The pharmaceutical composition may be an aqueous liquid preparation containing water as a solvent. By "aqueous liquid preparation", it is meant a liquid pharmaceutical composition comprising water as a solvent. The aqueous liquid preparation may be prepared by a conventional method such as dissolving or dispersing the respective components in water as a solvent, and may be a solution, a suspension or an emulsion.
Examples of the ophthalmic pharmaceutical composition include an eye drop (including an eye drop that can be used in a state in which a soft contact lens is worn, and also referred to as an eye drop and an eye drop), an eye lotion (including an eye lotion that can be used when a soft contact lens is worn, and also referred to as an eye lotion and an eye lotion), an eye ointment, a soft contact lens wearing solution, and a soft contact lens care agent (a cleaning solution, a storage solution, a bactericidal solution, and a disinfectant solution { including a multifunctional care solution } and the like), and the eye drop, the contact lens wearing solution, the eye lotion, and the soft contact lens care agent are preferable, and the eye drop is particularly preferable.
The pharmaceutical composition of the present invention includes an eye drop which can be used in a state where a soft contact lens is worn. That is, the pharmaceutical composition of the present invention can be applied to an eye with a soft contact lens. The type of the soft contact lens is not particularly limited, and disposable soft contact lenses, periodically replaceable soft contact lenses, existing soft contact lenses, silicone hydrogel contact lenses, and color contact lenses can be used. The silicone hydrogel contact lens is made of a silicone hydrogel material.
The administration and dose of the eye drops of the present invention vary depending on the symptoms, age, and the like of the patient, but in general, eye drops are administered 1 to 6 times per 1day, 1 to 3 drops per 1 time.
The container used for the pharmaceutical composition of the present invention is sterilized by a conventional method. The sterilization method is not particularly limited as long as it is a commonly used method, and examples thereof include dry heat sterilization, electron beam sterilization, gamma ray sterilization, and ethylene gas sterilization. In 1 embodiment, the sterilization treatment is electron beam sterilization.
The present invention also relates to a method for inhibiting adsorption of alkyldiaminoethylglycine to a soft contact lens, which is characterized in that the content of alkyldiaminoethylglycine hydrochloride in the pharmaceutical composition for a soft contact lens is 0.001 w/v% or more and 0.008 w/v% or less, and a metal chloride is blended in the pharmaceutical composition for a soft contact lens. In this method, adsorption of alkyldiaminoethylglycine to a soft contact lens is further effectively suppressed by blending glucose in addition to alkyldiaminoethylglycine hydrochloride and a metal chloride in the pharmaceutical composition for a soft contact lens.
In the above adsorption inhibiting method, the content of alkyldiaminoethylglycine hydrochloride in the pharmaceutical composition for a soft contact lens is limited to 0.001 w/v% or more and 0.008 w/v% or less based on: in such a low concentration range, the adsorption rate of alkyldiaminoethylglycine to soft contact lenses is improved.
In the above adsorption inhibition method, the kind and concentration of the alkyldiaminoethylglycine hydrochloride, the metal chloride, glucose, and other optional components used may be used alone or in combination with the above-mentioned pharmaceutical composition for soft contact lenses. The same applies to the pH, the container, and the like of the pharmaceutical composition for soft contact lenses.
The present application claims benefits based on the priority of japanese patent application No. 2019-217422, filed on day 29, 11/2019. The entire contents of the specification of japanese patent application No. 2019-217422, filed on 11/29/2019, are incorporated herein by reference.
Examples
The present invention will be described in more detail below with reference to examples, but the present invention is not limited to the examples described below, and may be carried out by adding modifications as appropriate within a range that can be adapted to the gist described above and below, and all of them are included in the technical scope of the present invention.
Test example 1: adsorptivity test for soft contact lenses
A solution having a composition shown in Table 1 was prepared by diluting a fixed amount of alkyldiaminoethylglycine hydrochloride solution ("レボン LAG-40" made by Sanyo chemical industry Co., Ltd.) with purified water, adding boric acid (made by Borax Francais) and Borax (made by Sakai chemical corporation) and adjusting the pH to 7 with hydrochloric acid. In addition, the values in the table are w/v%. Soft contact lenses belonging to group I ("シード 1dayFine UV plus" manufactured by シード Co., Ltd.) were washed with purified water. The aqueous solution (3mL) was measured in a vial, and 1 piece of the soft contact lens washed with purified water was immersed in the solution and shaken at 25 ℃ for 24 hours to prepare an SCL immersion solution. The aqueous solution not immersed in the soft contact lens was also shaken at 25 ℃ for 24 hours to prepare a control test solution. The above tests were carried out for each example 2. In the table, "ADG" represents alkyldiaminoethylglycine.
Separately, a quantitative alkyldiaminoethylglycine hydrochloride solution (62.5mg) was precisely weighed, and water was added to make the total volume accurately 100 mL. This liquid (2mL) was precisely weighed, and water was added to make the total volume to be exactly 20mL, thereby preparing a standard solution. The SCL-impregnated solution and a standard solution (50. mu.L) were precisely weighed, and the sum of the areas of the peaks of alkyldiaminoethylglycine was determined by liquid chromatography under the following conditions.
Column: cyanopropylsilylated silica gel having an inner diameter of 4.6mm and a length of 15cm ("CN 12S05-1546 WT", manufactured by ワイエムシィ Co., Ltd.)
A detector: ultraviolet absorption photometer
Measuring wavelength: 210nm
Mobile phase: methanol/phosphoric acid mixed solution for water/liquid chromatography (750/250/1)
The content of ADG in the SCL immersion liquid was determined from the sum of the measured ADG peak areas by the following formula, and the adsorption rate of ADG to the soft contact lens was further calculated. The results are shown in table 1.
Content of ADG hydrochloride (. mu.g/mL) in SCL-dipped solution or control test solution (weight) of ADG hydrochloride solution for quantification (mg). times.content of ADG hydrochloride solution for quantification (w/v%)/100/1.03/Ss×ST
[ in the formula, 1.03 represents ADG hydrochloride solution for quantificationDensity (g/cm)3),SsThe sum of the ADG peak areas, S, of the standard solutionsTThe sum of the areas of the ADG peaks in the SCL dips or control test solutions is shown.]
Further, the adsorption rate of ADG to the soft contact lens was calculated from the following equation. The results are shown in table 1.
Adsorption rate (%) of ADG hydrochloride was 100- [ (C)TAV/CCAV)×100]
[ in the formula, CTAVThe average content (. mu.g/mL) of ADG in the SCL immersion fluid, CCAVThe average ADG content (. mu.g/mL) in the control test solutions is shown.]
[ Table 1]
As shown in the results in table 1, it was confirmed that the lower the ADG concentration, the higher the ratio of ADG adsorbed on the soft contact lens tends to be.
Test example 2: investigation of raw Material for Soft contact lens
The SCL-impregnating solution and the control test solution for each of the soft contact lenses of groups I to IV shown in table 2 were obtained under the same conditions as in test example 1, except that reference example 2 of test example 1 was set as comparative example 1, and the preparation prepared by mixing 0.55 w/v% of sodium chloride (manufactured by マナック) in reference example 2 was set as example 1. Each example 3 was tested. Groups I to IV are classified by FDA (united states food and drug administration), group I has a water content of less than 50% and is nonionic, group II has a water content of 50% or more and is nonionic, group III has a water content of less than 50% and is ionic, and group IV has a water content of 50% or more and is ionic.
Separately, a quantitative alkyldiaminoethylglycine hydrochloride solution ("レボン LAG-40", manufactured by Sanyo chemical industries Co., Ltd.) (62.5mg) was precisely weighed, and water was added to make the total volume accurately 100 mL. To this liquid (5mL) was added an additive solution (25mL) prepared by dissolving boric acid (made by Borax Francais (0.5 g)) and Borax (made by Sakai pharmaceutical corporation) (40mg) in water to give a total volume of 50mL, and water was further added to give a total volume of 50mL, which was set to be a standard solution. In addition, to the addition solution (10mL), water was added to make the total volume accurately 20mL, which was set as a control solution.
In SCL immersion liquid, control test liquid, standard solution, and control solution (2mL), potassium dihydrogen phosphate (fuji フィルム and made by pure science and medicine) (3.4g) and eosin Y (fuji フィルム and made by pure science and medicine) (24mg) were dissolved in water and stirred so that the total volume was adjusted to 100mL of eosin solution (4mL), and with respect to these liquids, absorbance at a wavelength of 545nm was measured, the amount of ADG contained in SCL immersion liquid and control test liquid was obtained from the following formula, and the adsorption rate was further obtained in the same manner as in reference example 1. In addition, the adsorption inhibition ratio was also calculated. The results are shown in table 2. In table 2, "SHCL" represents a silicone hydrogel contact lens containing silicon, and when "ワンデーアキュビューモイスト" (manufactured by ジョンソン, エンド, ジョンソン) of group IV was used, the SCL was deformed, but the measurement was performed in the same manner as the other cases.
ADG HCl content (w/v%) in SCL immersion and control solutions (mg)/1.03 XM/100 Xof ADG HCl solution (A)T-AC)/(AS-AC)
[ in the formula, 1.03 represents the density (g/cm) of ADG hydrochloride solution for quantification3) M represents the concentration of ADG hydrochloride for quantification (w/v%), ATDenotes the absorbance of the SCL immersion fluid or of the control test fluid, ACDenotes the absorbance of the control solution, ASThe absorbance of the standard solution is shown.]
Adsorption inhibition ratio (%) ("ADG adsorption ratio (%) of comparative example 1 — ADG adsorption ratio (%) of example 1/ADG adsorption ratio (%) of comparative example 1) × 100
[ Table 2]
As shown in the results of table 2, it was confirmed that alkyldiaminoethylglycine tended to adsorb to the soft contact lens when the soft contact lens was immersed in a low concentration alkyldiaminoethylglycine hydrochloride solution of 0.0025 w/v%.
However, it is clear that: if sodium chloride is compounded in addition to the low concentration of alkyldiaminoethylglycine hydrochloride, adsorption of alkyldiaminoethylglycine is uniformly inhibited. It is found that such an adsorption inhibiting effect is particularly high when hydroxyethyl methacrylate (HEMA) is contained in the raw material of the soft contact lens.
Test example 3: effect of glucose addition
Under the same conditions as in test example 1, the adsorption rate of alkyldiaminoethylglycine to soft contact lenses and the adsorption inhibition rate of alkyldiaminoethylglycine to the preparation of comparative example 1 were determined using a preparation prepared by blending boric acid and borax in addition to alkyldiaminoethylglycine hydrochloride (comparative example 1) and a preparation further prepared by blending sodium chloride or sodium chloride and glucose (manufactured by サンエイ co., ltd.) and having a composition shown in table 3 (examples 1 to 3). In this test, "シード 1dayFine UV plus" manufactured by シード Co., Ltd., was used as a soft contact lens, and each example was 2. The results are shown in table 3.
[ Table 3]
As shown in the results in table 3, it was found that adsorption of alkyldiaminoethylglycine was inhibited by sodium chloride, and such an adsorption inhibiting effect was improved by using glucose in combination.
Further, it was confirmed that: the above-mentioned effects brought about by glucose are particularly high by compounding at relatively low concentrations.
Test example 4: effect of adding a metal chloride other than sodium chloride
The adsorption rate of alkyldiaminoethylglycine to soft contact lenses and the adsorption inhibition rate of the preparation of comparative example 1 containing alkyldiaminoethylglycine alone were determined under the same conditions as in test example 1 using the preparations having the compositions shown in table 4 prepared by mixing sodium chloride or potassium chloride (manufactured by akashiwo chemical corporation) or calcium chloride (manufactured by fuyoda pharmaceutical corporation) in place of sodium chloride. In this test, "シード 1dayFine UV plus" manufactured by シード corporation was used as soft contact lenses, and example 2 was each. The results are shown in table 4.
[ Table 4]
As shown in the results shown in table 4, it was found that the adsorption of alkyldiaminoethylglycine to the soft contact lens was inhibited not only by sodium chloride but also by other metal chlorides such as potassium chloride and calcium chloride.
Test example 5: investigation of sodium chloride concentration
The adsorption rate of alkyldiaminoethylglycine to soft contact lenses and the adsorption inhibition rate of the preparation of comparative example 1 containing alkyldiaminoethylglycine alone were determined under the same conditions as in test example 1 using the preparation having the composition shown in table 5 with the sodium chloride concentration changed. In this test, "シード 1dayFine UV plus" manufactured by シード Co., Ltd., was used as a soft contact lens, and each example was 2. The results are shown in table 5.
[ Table 5]
As shown in Table 5, the adsorption of alkyldiaminoethylglycine to soft contact lenses was suppressed by 0.1 to 0.8 w/v% sodium chloride, and the adsorption suppressing effect was slightly reduced in the case of 0.1 w/v%, but was almost equal in the range of 0.3 to 0.8 w/v%.
Test example 6: investigation of the concentration of alkyldiaminoethylglycine hydrochloride
Using the formulations having the compositions shown in table 6 in which the concentration of alkyldiaminoethylglycine hydrochloride was changed under the same conditions as in test example 1, the adsorption rate of alkyldiaminoethylglycine to soft contact lenses and the adsorption inhibition rate of alkyldiaminoethylglycine to the formulations containing the same concentration but not containing sodium chloride were determined. In this test, "シード 1dayFine UV plus" manufactured by シード Co., Ltd., was used as a soft contact lens, and examples 3 thereof were each used. The results are shown in table 6.
[ Table 6]
As shown in the results of table 6, it was found that the adsorption of alkyldiaminoethylglycine to soft contact lenses is effectively suppressed by sodium chloride as the concentration of alkyldiaminoethylglycine hydrochloride is lower, and particularly, is effectively suppressed when the concentration of alkyldiaminoethylglycine hydrochloride is 0.005 w/v% or less.
Test example 7: confirmation of Effect on tinted Soft contact lenses
Under the same conditions as in test example 1, using the formulations having the compositions shown in table 7, the adsorption rates of alkyldiaminoethylglycine to "ワンデーリフレアビジュー" manufactured by フロムアイズ and "トロンプルイユワンデー" manufactured by ビューフロンティア, which are colored soft contact lenses made from the same raw material as "シード 1dayFine UV plus" manufactured by シード, and the adsorption inhibition rate of alkyldiaminoethylglycine to a formulation (comparative example 4) containing the same concentration but not containing sodium chloride were determined. Each example 3 was tested. The results are shown in table 7.
[ Table 7]
As the results shown in table 7, it is clear that: the effect of suppressing adsorption of alkyldiaminoethylglycine to a soft contact lens by sodium chloride is also exerted on a colored soft contact lens (colored contact lens).
Test example 8: study of pH
Using a preparation having a composition shown in table 8, in which the pH was adjusted by hydrochloric acid or an aqueous sodium hydroxide solution, under the same conditions as in test example 1, the adsorption rate of alkyldiaminoethylglycine to a soft contact lens and the adsorption inhibition rate of alkyldiaminoethylglycine to a preparation containing the same concentration but not containing sodium chloride were determined. In this test, "シード 1dayFine UV plus" manufactured by シード Co., Ltd., was used as a soft contact lens, and examples 3 thereof were each used. The results are shown in table 8.
[ Table 8]
As the results shown in table 8, it is clear that: the effect of suppressing adsorption of alkyldiaminoethylglycine to a soft contact lens by sodium chloride is particularly remarkably exhibited in a range of pH 6.5 to 7.5.
Claims (15)
1. A pharmaceutical composition for soft contact lenses, which contains 0.001 to 0.008 w/v% of alkyldiaminoethylglycine hydrochloride and a metal chloride.
2. The pharmaceutical composition for soft contact lenses according to claim 1, wherein the metal chloride is at least 1 salt selected from the group consisting of alkali metal chlorides and group IIA metal chlorides.
3. The pharmaceutical composition for soft contact lenses according to claim 1, wherein the metal chloride is sodium chloride and/or potassium chloride.
4. A pharmaceutical composition for soft contact lenses according to any one of claims 1 to 3, which contains 0.05 w/v% or more and 5 w/v% or less of a metal chloride.
5. The pharmaceutical composition for soft contact lenses according to any one of claims 1 to 4, further comprising glucose.
6. The pharmaceutical composition for a soft contact lens according to claim 5, which contains 0.001 w/v% or more and 0.01 w/v% or less of glucose.
7. The pharmaceutical composition for a soft contact lens according to any one of claims 1 to 6, which comprises 0.001 w/v% or more and 0.005 w/v% or less of alkyldiaminoethylglycine hydrochloride and 0.5 w/v% or more and 1 w/v% or less of a metal chloride.
8. A pharmaceutical composition for soft contact lenses according to any one of claims 1 to 6, comprising:
0.001 to 0.005 w/v% of alkyldiaminoethylglycine hydrochloride,
0.5 to 1 w/v% of a metal chloride, and
0.002 w/v% or more and 0.008 w/v% or less of glucose.
9. The pharmaceutical composition for a soft contact lens according to any one of claims 1 to 8, further comprising a nonionic surfactant.
10. The pharmaceutical composition for a soft contact lens according to any one of claims 1 to 9, further comprising a buffer.
11. The pharmaceutical composition for a soft contact lens according to any one of claims 1 to 10, further comprising a thickener.
12. The pharmaceutical composition for a soft contact lens according to any one of claims 1 to 11, further comprising an amino acid.
13. A pharmaceutical composition for soft contact lenses according to any one of claims 1 to 12, comprising:
0.001 to 0.008 w/v% of alkyldiaminoethylglycine hydrochloride,
0.1 to 2.0 w/v% of a metal chloride,
0.002 to 0.008 w/v% of glucose,
0.005 to 0.05 w/v% of polyoxyethylene hydrogenated castor oil,
A buffer agent of 0.1 to 2.0 w/v%,
0.05 w/v% or more and 0.5 w/v% or less of a thickener, and
0.05 w/v% or more and 1.0 w/v% or less of an amino acid.
14. The pharmaceutical composition for a soft contact lens according to any one of claims 1 to 13, which has a pH of 5.5 or more and 8.0 or less.
15. The pharmaceutical composition for a soft contact lens according to any one of claims 1 to 13, which has a pH of 6.5 or more and 7.5 or less.
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PCT/JP2020/044070 WO2021107035A1 (en) | 2019-11-29 | 2020-11-26 | Pharmaceutical composition for soft contact lens |
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0368503A (en) * | 1989-08-08 | 1991-03-25 | Rohto Pharmaceut Co Ltd | Liquid medicine for contact lens |
JP2003300871A (en) * | 2002-04-08 | 2003-10-21 | Lion Corp | Ophthalmic composition |
JP2013032393A (en) * | 2012-11-09 | 2013-02-14 | Rohto Pharmaceutical Co Ltd | Eye drop for contact lens containing refrigerative agent |
CN105960606A (en) * | 2014-02-06 | 2016-09-21 | Jsr株式会社 | Lens solution, contact lens, and production method therefor |
-
2020
- 2020-11-26 WO PCT/JP2020/044070 patent/WO2021107035A1/en active Application Filing
- 2020-11-26 JP JP2021561507A patent/JP7250167B2/en active Active
- 2020-11-26 CN CN202080082048.5A patent/CN114786650A/en active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0368503A (en) * | 1989-08-08 | 1991-03-25 | Rohto Pharmaceut Co Ltd | Liquid medicine for contact lens |
JP2003300871A (en) * | 2002-04-08 | 2003-10-21 | Lion Corp | Ophthalmic composition |
JP2013032393A (en) * | 2012-11-09 | 2013-02-14 | Rohto Pharmaceutical Co Ltd | Eye drop for contact lens containing refrigerative agent |
CN105960606A (en) * | 2014-02-06 | 2016-09-21 | Jsr株式会社 | Lens solution, contact lens, and production method therefor |
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