JP2006176501A - Ophthalmic medicine - Google Patents
Ophthalmic medicine Download PDFInfo
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- JP2006176501A JP2006176501A JP2005340432A JP2005340432A JP2006176501A JP 2006176501 A JP2006176501 A JP 2006176501A JP 2005340432 A JP2005340432 A JP 2005340432A JP 2005340432 A JP2005340432 A JP 2005340432A JP 2006176501 A JP2006176501 A JP 2006176501A
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- water
- soluble polymer
- eye
- ophthalmic
- irritation
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- 229940023490 ophthalmic product Drugs 0.000 title abstract 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 26
- 229920003169 water-soluble polymer Polymers 0.000 claims abstract description 25
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 claims abstract description 24
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 claims abstract description 17
- 229940041616 menthol Drugs 0.000 claims abstract description 13
- 229960004926 chlorobutanol Drugs 0.000 claims abstract description 12
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims abstract description 11
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims abstract description 11
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims abstract description 10
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound 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 claims abstract description 10
- 229920002451 polyvinyl alcohol Polymers 0.000 claims abstract description 8
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims abstract description 7
- 239000004372 Polyvinyl alcohol Substances 0.000 claims abstract description 7
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims abstract description 6
- 229920002125 Sokalan® Polymers 0.000 claims abstract description 6
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims abstract description 6
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims abstract description 6
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims abstract description 6
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims abstract description 5
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 claims abstract 2
- 239000003732 agents acting on the eye Substances 0.000 claims description 19
- 229940125702 ophthalmic agent Drugs 0.000 claims description 19
- 229920000609 methyl cellulose Polymers 0.000 claims description 5
- 239000001923 methylcellulose Substances 0.000 claims description 5
- -1 methylcellose Polymers 0.000 abstract description 5
- 235000011837 pasties Nutrition 0.000 abstract 1
- 230000007794 irritation Effects 0.000 description 19
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 15
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 15
- 239000002997 ophthalmic solution Substances 0.000 description 12
- 229940054534 ophthalmic solution Drugs 0.000 description 10
- 206010013774 Dry eye Diseases 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 238000002156 mixing Methods 0.000 description 8
- 239000008213 purified water Substances 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 208000003556 Dry Eye Syndromes Diseases 0.000 description 7
- 239000000607 artificial tear Substances 0.000 description 7
- 238000011156 evaluation Methods 0.000 description 7
- 239000003889 eye drop Substances 0.000 description 7
- 208000003464 asthenopia Diseases 0.000 description 6
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 6
- 239000004327 boric acid Substances 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 6
- 229940031705 hydroxypropyl methylcellulose 2910 Drugs 0.000 description 6
- 230000003204 osmotic effect Effects 0.000 description 6
- 206010015946 Eye irritation Diseases 0.000 description 5
- 229960000686 benzalkonium chloride Drugs 0.000 description 5
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 5
- 229940012356 eye drops Drugs 0.000 description 5
- 231100000013 eye irritation Toxicity 0.000 description 5
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 235000010981 methylcellulose Nutrition 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 239000001509 sodium citrate Substances 0.000 description 4
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000006196 drop Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 229920000139 polyethylene terephthalate Polymers 0.000 description 3
- 239000005020 polyethylene terephthalate Substances 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 239000002826 coolant Substances 0.000 description 2
- RMRCNWBMXRMIRW-BYFNXCQMSA-M cyanocobalamin Chemical compound N#C[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O RMRCNWBMXRMIRW-BYFNXCQMSA-M 0.000 description 2
- OSZNNLWOYWAHSS-UHFFFAOYSA-M neostigmine methyl sulfate Chemical compound COS([O-])(=O)=O.CN(C)C(=O)OC1=CC=CC([N+](C)(C)C)=C1 OSZNNLWOYWAHSS-UHFFFAOYSA-M 0.000 description 2
- 229960002253 neostigmine methylsulfate Drugs 0.000 description 2
- 230000035807 sensation Effects 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 238000002636 symptomatic treatment Methods 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 1
- CIVCELMLGDGMKZ-UHFFFAOYSA-N 2,4-dichloro-6-methylpyridine-3-carboxylic acid Chemical compound CC1=CC(Cl)=C(C(O)=O)C(Cl)=N1 CIVCELMLGDGMKZ-UHFFFAOYSA-N 0.000 description 1
- SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 1
- DBAKFASWICGISY-BTJKTKAUSA-N Chlorpheniramine maleate Chemical compound OC(=O)\C=C/C(O)=O.C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 DBAKFASWICGISY-BTJKTKAUSA-N 0.000 description 1
- 241000723346 Cinnamomum camphora Species 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 description 1
- SNPLKNRPJHDVJA-ZETCQYMHSA-N D-panthenol Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCCO SNPLKNRPJHDVJA-ZETCQYMHSA-N 0.000 description 1
- IMROMDMJAWUWLK-UHFFFAOYSA-N Ethenol Chemical compound OC=C IMROMDMJAWUWLK-UHFFFAOYSA-N 0.000 description 1
- XLRHXNIVIZZOON-WFUPGROFSA-L Flavin adenine dinucleotide disodium Chemical compound [Na+].[Na+].C1=NC2=C(N)N=CN=C2N1[C@@H]([C@H](O)[C@@H]1O)O[C@@H]1COP([O-])(=O)OP([O-])(=O)OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C2=NC(=O)NC(=O)C2=NC2=C1C=C(C)C(C)=C2 XLRHXNIVIZZOON-WFUPGROFSA-L 0.000 description 1
- 206010016807 Fluid retention Diseases 0.000 description 1
- 239000004378 Glycyrrhizin Substances 0.000 description 1
- DJDFFEBSKJCGHC-UHFFFAOYSA-N Naphazoline Chemical compound Cl.C=1C=CC2=CC=CC=C2C=1CC1=NCCN1 DJDFFEBSKJCGHC-UHFFFAOYSA-N 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 1
- 229930003779 Vitamin B12 Natural products 0.000 description 1
- 229930003471 Vitamin B2 Natural products 0.000 description 1
- 230000004308 accommodation Effects 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229960002684 aminocaproic acid Drugs 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 229910021538 borax Inorganic materials 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229960000846 camphor Drugs 0.000 description 1
- 229930008380 camphor Natural products 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 229920003174 cellulose-based polymer Polymers 0.000 description 1
- 229940046978 chlorpheniramine maleate Drugs 0.000 description 1
- KXKPYJOVDUMHGS-OSRGNVMNSA-N chondroitin sulfate Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](OS(O)(=O)=O)[C@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](C(O)=O)O1 KXKPYJOVDUMHGS-OSRGNVMNSA-N 0.000 description 1
- AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 235000000639 cyanocobalamin Nutrition 0.000 description 1
- 239000011666 cyanocobalamin Substances 0.000 description 1
- 229960002104 cyanocobalamin Drugs 0.000 description 1
- 229960000525 diphenhydramine hydrochloride Drugs 0.000 description 1
- KCIDZIIHRGYJAE-YGFYJFDDSA-L dipotassium;[(2r,3r,4s,5r,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] phosphate Chemical compound [K+].[K+].OC[C@H]1O[C@H](OP([O-])([O-])=O)[C@H](O)[C@@H](O)[C@H]1O KCIDZIIHRGYJAE-YGFYJFDDSA-L 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229960004756 ethanol Drugs 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000010642 eucalyptus oil Substances 0.000 description 1
- 229940044949 eucalyptus oil Drugs 0.000 description 1
- FVTCRASFADXXNN-SCRDCRAPSA-N flavin mononucleotide Chemical compound OP(=O)(O)OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O FVTCRASFADXXNN-SCRDCRAPSA-N 0.000 description 1
- 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 description 1
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 description 1
- 229960004949 glycyrrhizic acid Drugs 0.000 description 1
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 1
- 235000019410 glycyrrhizin Nutrition 0.000 description 1
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 1
- 230000007803 itching Effects 0.000 description 1
- 239000001525 mentha piperita l. herb oil Substances 0.000 description 1
- 229940080927 menthol 10 mg Drugs 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- 229960004760 naphazoline hydrochloride Drugs 0.000 description 1
- 229960002362 neostigmine Drugs 0.000 description 1
- LULNWZDBKTWDGK-UHFFFAOYSA-M neostigmine bromide Chemical compound [Br-].CN(C)C(=O)OC1=CC=CC([N+](C)(C)C)=C1 LULNWZDBKTWDGK-UHFFFAOYSA-M 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 229940101267 panthenol Drugs 0.000 description 1
- 239000011619 pantothenol Substances 0.000 description 1
- 235000020957 pantothenol Nutrition 0.000 description 1
- 235000019477 peppermint oil Nutrition 0.000 description 1
- OCYSGIYOVXAGKQ-FVGYRXGTSA-N phenylephrine hydrochloride Chemical compound [H+].[Cl-].CNC[C@H](O)C1=CC=CC(O)=C1 OCYSGIYOVXAGKQ-FVGYRXGTSA-N 0.000 description 1
- 229960003733 phenylephrine hydrochloride Drugs 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229920006316 polyvinylpyrrolidine Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- ZUFQODAHGAHPFQ-UHFFFAOYSA-N pyridoxine hydrochloride Chemical compound Cl.CC1=NC=C(CO)C(CO)=C1O ZUFQODAHGAHPFQ-UHFFFAOYSA-N 0.000 description 1
- 229960004172 pyridoxine hydrochloride Drugs 0.000 description 1
- 235000019171 pyridoxine hydrochloride Nutrition 0.000 description 1
- 239000011764 pyridoxine hydrochloride Substances 0.000 description 1
- 229960002477 riboflavin Drugs 0.000 description 1
- 229950001574 riboflavin phosphate Drugs 0.000 description 1
- 239000004328 sodium tetraborate Substances 0.000 description 1
- 235000010339 sodium tetraborate Nutrition 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 229960003080 taurine Drugs 0.000 description 1
- BJORNXNYWNIWEY-UHFFFAOYSA-N tetrahydrozoline hydrochloride Chemical compound Cl.N1CCN=C1C1C2=CC=CC=C2CCC1 BJORNXNYWNIWEY-UHFFFAOYSA-N 0.000 description 1
- 229940021790 tetrahydrozoline hydrochloride Drugs 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 235000019163 vitamin B12 Nutrition 0.000 description 1
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- 235000019164 vitamin B2 Nutrition 0.000 description 1
- 239000011716 vitamin B2 Substances 0.000 description 1
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- Medicinal Preparation (AREA)
Abstract
Description
本発明は、眼科用剤に関し、より具体的には、水溶性高分子を配合する使用感が改善された眼科用剤に関する。 The present invention relates to an ophthalmic agent, and more specifically to an ophthalmic agent having an improved usability when a water-soluble polymer is blended.
最近では、パソコンなどの電子端末（ＶＤＴ）を用いる作業ではディスプレーを注視する状態が続き、眼のかわき（ドライアイ症状）を引き起こし、それによって眼に負担がかかり、眼が疲労すると指摘されている（非特許文献１）。 Recently, it has been pointed out that work using a computer or other electronic terminal (VDT) continues to watch the display, causing eye dryness (dry eye symptoms), which puts strain on the eye and causes eye fatigue. (Non-Patent Document 1).
ドライアイとは、涙液の減少又は質的な異常そのものを指す場合や、涙液の量的又は質的異常により角結膜に障害を来した状態を意味する。自覚症状としては目の疲労、ゴロゴロ感、乾燥感、不快感、かすみ、かゆみ、痛み、遠近調節不良、目やに・涙の多寡などとして現れ、日常生活に大きな支障を来す疾患である。 Dry eye refers to a decrease in tears or a qualitative abnormality itself, or a state in which the keratoconjunctiva is damaged due to a quantitative or qualitative abnormality of tears. As subjective symptoms, it is a disease that appears as fatigue of the eyes, a feeling of dryness, a feeling of dryness, discomfort, blurring, itching, pain, poor accommodation control, a lot of eyes and tears, etc., and has a major impact on daily life.
眼のかわき、眼の疲労やドライアイに対して、有効な薬剤や確実な治療法は無く、現在、自覚症状を軽減させる対症療法が取られている。対症療法の例としては、眼のかわきには、人工涙液と言われる点眼液等が使用されている。また眼の疲労やドライアイを緩和・改善するためには、ビタミンＢ２やビタミンＢ１２等のビタミン類、タウリン、メチル硫酸ネオスチグミン等を配合した点眼液や人工涙液等が使用されている。 There are no effective drugs or reliable treatments for eye dryness, eye fatigue, and dry eye. Currently, symptomatic treatment is being taken to reduce subjective symptoms. As an example of symptomatic treatment, eye drops or the like called artificial tears are used to clean the eyes. In order to relieve and improve eye fatigue and dry eye, ophthalmic solutions or artificial tears containing vitamins such as vitamin B2 and vitamin B12, taurine, neostigmine methyl sulfate, and the like are used.
眼のかわきを防ぎ、涙液の保水性を高める目的でコラーゲンペプチドを必須成分とする人工涙液が特許文献１に開示されており、涙液の粘性を高める目的で水溶性高分子を配合する人工涙液が特許文献２に開示されている。また、清涼感の持続を目的とした水溶性高分子を配合する点眼剤が特許文献３（水溶性高分子と清涼化剤の配合）や特許文献４（水溶性高分子と低級アルコールの配合）に開示されている。 An artificial tear containing collagen peptide as an essential component for the purpose of preventing eye irritation and improving water retention of tears is disclosed in Patent Document 1, and a water-soluble polymer is added for the purpose of increasing the viscosity of tears. Artificial tears are disclosed in Patent Document 2. Further, eye drops containing a water-soluble polymer for the purpose of maintaining a refreshing sensation are disclosed in Patent Document 3 (formulation of water-soluble polymer and cooling agent) and Patent Document 4 (formulation of water-soluble polymer and lower alcohol). Is disclosed.
しかしながら、（ａ）水溶性高分子、（ｂ）エタノール、（ｃ）メントール及び（ｄ）クロロブタノールを同時に含有する眼科用剤の開示はない。 However, there is no disclosure of an ophthalmic agent containing (a) a water-soluble polymer, (b) ethanol, (c) menthol and (d) chlorobutanol at the same time.
水溶性高分子を配合する眼科用剤には、特有のべたつき感があり、使用感が悪く、使用感の改善が求められていた。 An ophthalmic agent containing a water-soluble polymer has a peculiar stickiness, has a poor usability, and has been required to improve the usability.
本発明の目的は、使用時の不快なべたつき感が改善され、刺激の無い眼科用剤を提供することである。 An object of the present invention is to provide an ophthalmic preparation which is improved in unpleasant stickiness during use and free from irritation.
目のかわきや効果の持続化のために眼科用剤に水溶性高分子を配合されているが、水溶性高分子を配合した眼科用剤は、使用時にべたつくため使用感が悪く改善が望まれる。メントールを配合すると、清涼感を付与することでべたつきを改善することができるが、強めの清涼感を付与しないとべたつきを完全にマスキングすることが出来ないことが判明した。また、強めの清涼感を付与するために、メントールを多く配合すると刺激が生じてしまう。そこで、クロロブタノールを配合することにより、べたつき感と刺激も緩和し、更にメントールによる点眼直後の過度な清涼感をマスキングし、適度な清涼感を維持することが可能になった。更に、エタノールを配合することにより、点眼時に生じる刺激を緩和させることも見出した。また、２５℃における絶対粘度が１５ｍＰａ・ｓを超えるとべたつきが改善できないことも見出した。 A water-soluble polymer is blended with an ophthalmic agent to keep the eyes clean and the effect is effective. However, an ophthalmic agent blended with a water-soluble polymer is sticky at the time of use, so the feeling of use is poor and improvement is desired. . When menthol was blended, it was found that stickiness could be improved by imparting a refreshing feeling, but stickiness could not be completely masked unless a strong refreshing feeling was imparted. In addition, when a large amount of menthol is added to give a strong refreshing feeling, irritation occurs. Therefore, by adding chlorobutanol, it was possible to relieve the stickiness and irritation, mask the excessive refreshing feeling immediately after instillation with menthol, and maintain an appropriate refreshing feeling. Furthermore, it discovered that the irritation | stimulation produced at the time of instillation was relieve | moderated by mix | blending ethanol. It was also found that stickiness cannot be improved when the absolute viscosity at 25 ° C. exceeds 15 mPa · s.
本発明者らは、上記のように鋭意研究した結果、水溶性高分子、エタノール、メントール０．００５〜０．０４０ｗ／ｖ％及びクロロブタノールを同時に配合し、２５℃における絶対粘度が１．３〜１５ｍＰａ・ｓである眼科用剤が、使用時の不快なべたつき感を改善し、適切な清涼感があり、刺激の無い眼科用剤となること見出し、本発明を完成した。 As a result of intensive research as described above, the present inventors have simultaneously blended water-soluble polymer, ethanol, menthol 0.005 to 0.040 w / v% and chlorobutanol, and the absolute viscosity at 25 ° C. is 1.3. It was found that an ophthalmic preparation having a viscosity of ˜15 mPa · s improves an unpleasant stickiness during use, has an appropriate refreshing feeling, and is an ophthalmic preparation without irritation, thereby completing the present invention.
すなわち、本発明の眼科用剤は、
１．（ａ）水溶性高分子、（ｂ）エタノール、（ｃ）メントール０．００５〜０．０４０ｗ／ｖ％及び（ｄ）クロロブタノールを含有する２５℃における絶対粘度が１．３〜１５ｍＰａ・ｓであることを特徴とする眼科用剤である。
２．（ａ）水溶性高分子が、ヒドロキシプロピルメチルセルロース、ヒドロキシエチルセルロース、カルボキシビニルポリマー、メチルセルロース、ポリビニルピロリドン及びポリビニルアルコールから選ばれる１種以上である上記１に記載の眼科用剤である。
３．水溶性高分子が、ヒドロキシプロピルメチルセルロースである上記１に記載の眼科用剤である。
That is, the ophthalmic agent of the present invention is
1. (A) Water-soluble polymer, (b) Ethanol, (c) Menthol 0.005-0.040 w / v% and (d) Absolute viscosity at 25 ° C. containing chlorobutanol is 1.3-15 mPa · s. It is an ophthalmic agent characterized by being.
2. (A) The ophthalmic agent according to 1 above, wherein the water-soluble polymer is at least one selected from hydroxypropylmethylcellulose, hydroxyethylcellulose, carboxyvinyl polymer, methylcellulose, polyvinylpyrrolidone, and polyvinyl alcohol.
3. 2. The ophthalmic agent according to 1 above, wherein the water-soluble polymer is hydroxypropylmethylcellulose.
本発明により、眼のかわき、眼の疲労やドライアイの緩和に有用であり、使用時のべたつき感が改善され、刺激の無い使用感の良い眼科用剤を提供することができる。 INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide an ophthalmic agent that is useful for relieving eye irritation, eye fatigue, and dry eye, has improved stickiness during use, and has a good feeling of use without irritation.
本発明で、水溶性高分子とは、眼科用剤に粘性を与える成分であり、例えば、セルロース系高分子、ビニル系高分子などであり、好ましくは、ヒドロキシプロピルメチルセルロース、ヒドロキシエチルセルロース、カルボキシビニルポリマー、メチルセルロース、ポリビニルピロリドン又はポリビニルアルコールであり、最も好ましくは、ヒドロキシプロピルメチルセルロースである。特に、ヒドロキシプロピルメチルセルロースのメトキシル基置換度が１５〜３５％が好ましい。最も好ましくは、メトキシル基置換度が２７〜３０％である。水溶性高分子は１種又は２種以上配合することができる。 In the present invention, the water-soluble polymer is a component that imparts viscosity to an ophthalmic agent, such as a cellulose-based polymer, a vinyl-based polymer, and preferably hydroxypropylmethylcellulose, hydroxyethylcellulose, carboxyvinyl polymer. Methyl cellulose, polyvinyl pyrrolidone or polyvinyl alcohol, and most preferably hydroxypropyl methyl cellulose. In particular, the substitution degree of methoxyl group of hydroxypropylmethylcellulose is preferably 15 to 35%. Most preferably, the degree of methoxyl group substitution is 27-30%. One or more water-soluble polymers can be blended.
水溶性高分子の配合量は、ヒドロキシプロピルメチルセルロース、ヒドロキシエチルセルロース、カルボキシビニルポリマー、メチルセルロースの場合は、好ましくは０．０１〜２．０ｗ／ｖ％であり、最も好ましくは０．０５〜１．０ｗ／ｖ％である。０．０１ｗ／ｖ％を下回ると十分に眼のかわきの緩和ができず、２．０ｗ／ｖ％を上回ると粘性が高くなり使用感が悪くなる。また、ポリビニルピロリドン、ポリビニルアルコールの場合は、好ましくは０．０５〜１０ｗ／ｖ％であり、最も好ましくは０．１〜５ｗ／ｖ％である。０．０５ｗ／ｖ％を下回ると十分に眼のかわきの緩和ができず、１０ｗ／ｖ％を上回ると刺激が強くなり使用感が悪くなる。 In the case of hydroxypropylmethylcellulose, hydroxyethylcellulose, carboxyvinyl polymer, and methylcellulose, the blending amount of the water-soluble polymer is preferably 0.01 to 2.0 w / v%, most preferably 0.05 to 1.0 w. / V%. If it is less than 0.01 w / v%, it is not possible to sufficiently relieve eye contact, and if it exceeds 2.0 w / v%, the viscosity becomes high and the feeling of use becomes worse. Moreover, in the case of polyvinylpyrrolidone and polyvinyl alcohol, it is preferably 0.05 to 10 w / v%, most preferably 0.1 to 5 w / v%. If it is less than 0.05 w / v%, it is not possible to sufficiently relieve eye irritation, and if it exceeds 10 w / v%, the irritation becomes strong and the feeling of use becomes worse.
本発明の眼科用剤の２５℃における絶対粘度は、１．３〜１５ｍＰａ・ｓである。粘度が１．３ｍＰａ・ｓ未満であると、目標とする眼のかわきを改善する効果が得られない。また、１５ｍＰａ・ｓを越えると、使用時にべたつきが生じる。 The absolute viscosity of the ophthalmic preparation of the present invention at 25 ° C. is 1.3 to 15 mPa · s. If the viscosity is less than 1.3 mPa · s, the effect of improving the target eye contact cannot be obtained. On the other hand, if it exceeds 15 mPa · s, stickiness occurs during use.
エタノールの配合量は、好ましくは０．０１〜１．０ｗ／ｖ％である。最も好ましくは、０．０５〜０．５ｗ／ｖ％である。０．０１ｗ／ｖ％を下回ると十分にべたつき感を改善できず、１．０ｗ／ｖ％を上回ると眼に刺激を与える。 The blending amount of ethanol is preferably 0.01 to 1.0 w / v%. Most preferably, it is 0.05-0.5 w / v%. If it is less than 0.01 w / v%, the sticky feeling cannot be improved sufficiently, and if it exceeds 1.0 w / v%, the eye is irritated.
メントールの配合量は、好ましくは０．００５〜０．０４ｗ／ｖ％であり、最も好ましくは０．０１０〜０．０３５ｗ／ｖ％である。０．００５％を下回ると十分にべたつき感を改善できず好ましい使用感を得ることができない。また０．０４ｗ／ｖ％を上回ると使用時に強い刺激を与える。 The blending amount of menthol is preferably 0.005 to 0.04 w / v%, and most preferably 0.010 to 0.035 w / v%. If it is less than 0.005%, the stickiness cannot be sufficiently improved, and a preferable feeling of use cannot be obtained. Moreover, when it exceeds 0.04 w / v%, a strong irritation | stimulation is given at the time of use.
クロロブタノールの配合量は、好ましくは０．０１〜０．４ｗ／ｖ％であり、最も好ましくは０．０５〜０．３ｗ／ｖ％であり、０．０１ｗ／ｖ％を下回ると使用時に強い刺激を与え、０．４ｗ／ｖ％を上回ると眼に障害を与える。
The blending amount of chlorobutanol is preferably 0.01 to 0.4 w / v%, most preferably 0.05 to 0.3 w / v%, and if it is less than 0.01 w / v%, it is strong during use. When irritation is applied and the concentration exceeds 0.4 w / v%, the eye is damaged.
更に、本発明の眼科用剤は、浸透圧を２５０〜４５０ｍＯｓｍ、ｐＨを４．０〜９．０に調整することが好ましい。特にドライアイの緩和を目的とする場合は、浸透圧を２８０〜３５０ｍＯｓｍ、ｐＨを５．０〜７．５に調整することが好ましい
ｐＨ調整剤は、無機性又は有機性のどちらでも良く、例えば、ホウ酸、リン酸、クエン酸とそれらの塩や塩酸、水酸化ナトリウムなどである。
Furthermore, it is preferable that the ophthalmic agent of the present invention adjusts the osmotic pressure to 250 to 450 mOsm and the pH to 4.0 to 9.0. Particularly for the purpose of alleviating dry eye, it is preferable to adjust the osmotic pressure to 280 to 350 mOsm and the pH to 5.0 to 7.5. The pH adjuster may be either inorganic or organic. Boric acid, phosphoric acid, citric acid and their salts, hydrochloric acid, sodium hydroxide and the like.
本発明の眼科用剤には、眼科用剤の安定性に影響を与えない範囲で、必要に応じて、医薬上許容される他の成分を配合することができ、例えば、イプシロンアミノカプロン酸、グリチルリチン酸二カリウム等の抗炎症薬、マレイン酸クロルフェニラミン、塩酸ジフェンヒドラミン等の抗ヒスタミン薬、塩酸テトラヒドロゾリン、塩酸フェニレフリン、塩酸ナファゾリン等の血管収縮薬、塩酸ピリドキシン、リン酸リボフラビン、シアノコバラミン、パンテノール、酢酸トコフェノール、フラビンアデニンジヌクレオチドナトリウム等のビタミン類、メチル硫酸ネオスチグミン等のピント調節薬、コンドロイチン硫酸ナトリウム、アミノエチルスルホン酸等のアミノ酸類、カンフル、ハッカ油又はユーカリ油等の清涼化剤、塩化ナトリウム、塩化カリウム等の無機塩類、ポリオキシエチレン硬化ヒマシ油、ポリオキシエチレンソルビタンモノオレート等の界面活性剤、その他基剤成分として、ホウ砂、ホウ酸、塩化ベンザルコニウム、パラオキシ安息香酸エステル（パラオキシ安息香酸メチル、パラオキシ安息香酸エチル、パラオキシ安息香酸プロピル、パラオキシ安息香酸ブチル等）等を挙げることができる。 In the ophthalmic agent of the present invention, other pharmaceutically acceptable components can be blended as necessary within a range that does not affect the stability of the ophthalmic agent. For example, epsilon aminocaproic acid, glycyrrhizin Anti-inflammatory drugs such as dipotassium acid, chlorpheniramine maleate, antihistamines such as diphenhydramine hydrochloride, vasoconstrictors such as tetrahydrozoline hydrochloride, phenylephrine hydrochloride, naphazoline hydrochloride, pyridoxine hydrochloride, riboflavin phosphate, cyanocobalamin, panthenol, acetic acid Vitamins such as tocophenol and flavin adenine dinucleotide sodium, focus regulators such as neostigmine methyl sulfate, amino acids such as sodium chondroitin sulfate and aminoethyl sulfonic acid, cooling agents such as camphor, peppermint oil or eucalyptus oil, sodium chloride ,salt Inorganic salts such as potassium, surfactants such as polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan monooleate, and other base components such as borax, boric acid, benzalkonium chloride, paraoxybenzoic acid ester (paraoxybenzoic acid) Methyl, ethyl paraoxybenzoate, propyl paraoxybenzoate, butyl paraoxybenzoate, etc.).
本発明で眼科用剤とは、一般の疲れ目用の点眼液、人工涙液、洗眼液等を示し、一般の疲れ目用点眼液及び人工涙液は、１日数回、１回１滴から数滴投与することができる。洗眼液は、１日数回、１回適量を使用することができる。 In the present invention, the ophthalmic agent refers to general eye drops for eye fatigue, artificial tears, eye wash, etc., and general eye drops for eye drops and artificial tears can be used several times a day, from one drop at a time. Several drops can be administered. An appropriate amount of the eye wash can be used several times a day.
以下、本発明の実施例及び試験例を示し、詳細に説明する。 Hereinafter, examples and test examples of the present invention will be shown and described in detail.
ヒドロキシプロピルメチルセルロース2910 250mg
エタノール 100mg
ｌ-メントール 28mg
クロロブタノール 250mg
クエン酸 10mg
クエン酸ナトリウム 100mg
塩化ベンザルコニウム 5mg
ホウ酸 500mg
希塩酸 適量
塩化ナトリウム 612mg
精製水 適量
ヒドロキシプロピルメチルセルロース2910を約70℃に加温した精製水に分散させた後、室温に冷却し溶解させた。ここに残りの各成分を溶解し、希塩酸でｐＨ５．２に調整して、精製水で全量を１００ｍＬにした。得られた点眼液をポリエチレンテレフタレート(PET)製点眼容器に無菌充填した。この点眼液の浸透圧は３３７ｍＯｓｍであった。
Hydroxypropyl methylcellulose 2910 250mg
Ethanol 100mg
l-Menthol 28mg
Chlorobutanol 250mg
Citric acid 10mg
Sodium citrate 100mg
Benzalkonium chloride 5mg
Boric acid 500mg
Dilute hydrochloric acid appropriate amount Sodium chloride 612mg
Purified water appropriate amount Hydroxypropyl methylcellulose 2910 was dispersed in purified water heated to about 70 ° C., and then cooled to room temperature and dissolved. The remaining components were dissolved therein, adjusted to pH 5.2 with dilute hydrochloric acid, and made up to 100 mL with purified water. The obtained ophthalmic solution was aseptically filled into an ophthalmic container made of polyethylene terephthalate (PET). The osmotic pressure of this ophthalmic solution was 337 mOsm.
ヒドロキシプロピルメチルセルロース2910 250mg
エタノール 500mg
ｌ-メントール 28mg
クロロブタノール 250mg
クエン酸 10mg
クエン酸ナトリウム 100mg
塩化ベンザルコニウム 5mg
ホウ酸 500mg
希塩酸 適量
塩化ナトリウム 339mg
精製水 適量
実施例１と同様の方法で点眼液とした。この点眼液の浸透圧は３３７ｍＯｓｍであった
Hydroxypropyl methylcellulose 2910 250mg
Ethanol 500mg
l-Menthol 28mg
Chlorobutanol 250mg
Citric acid 10mg
Sodium citrate 100mg
Benzalkonium chloride 5mg
Boric acid 500mg
Dilute hydrochloric acid appropriate amount Sodium chloride 339mg
Purified water Appropriate amount An ophthalmic solution was prepared in the same manner as in Example 1. The osmotic pressure of this ophthalmic solution was 337 mOsm.
メチル硫酸ネオスチグミン 5mg
ヒドロキシプロピルメチルセルロース2910 250mg
エタノール 1000mg
ｌ-メントール 28mg
クロロブタノール 250mg
クエン酸 10mg
クエン酸ナトリウム 100mg
塩化ベンザルコニウム 5mg
ホウ酸 500mg
希塩酸 適量
精製水 適量
実施例１と同様の方法で点眼液とした。この点眼液の浸透圧は３２９ｍＯｓｍであった。
Methyl sulfate neostigmine 5mg
Hydroxypropyl methylcellulose 2910 250mg
Ethanol 1000mg
l-Menthol 28mg
Chlorobutanol 250mg
Citric acid 10mg
Sodium citrate 100mg
Benzalkonium chloride 5mg
Boric acid 500mg
Dilute hydrochloric acid Appropriate amount Purified water Appropriate amount An ophthalmic solution was prepared in the same manner as in Example 1. The osmotic pressure of this ophthalmic solution was 329 mOsm.
ヒドロキシプロピルメチルセルロース2910 100mg
エタノール 100mg
ｌ-メントール 10mg
クロロブタノール 100mg
クエン酸 10mg
クエン酸ナトリウム 100mg
塩化ベンザルコニウム 5mg
ホウ酸 500mg
塩化ナトリウム 340mg
希塩酸 適量
精製水 適量
ヒドロキシプロピルメチルセルロース2910を約70℃に加温した精製水に分散させた後、室温に冷却し溶解させた。ここに残りの各成分を溶解し、希塩酸でｐＨ５．８に調整して、精製水で全量を１００ｍＬにした。得られた洗眼液をPET製容器に無菌充填した。この洗眼液の浸透圧は３３５ｍＯｓｍであった。
Hydroxypropyl methylcellulose 2910 100mg
Ethanol 100mg
l-Menthol 10mg
Chlorobutanol 100mg
Citric acid 10mg
Sodium citrate 100mg
Benzalkonium chloride 5mg
Boric acid 500mg
Sodium chloride 340mg
Dilute hydrochloric acid Appropriate amount of purified water Appropriate amount Hydroxypropylmethylcellulose 2910 was dispersed in purified water heated to about 70 ° C., and then cooled to room temperature and dissolved. The remaining components were dissolved therein, adjusted to pH 5.8 with dilute hydrochloric acid, and made up to 100 mL with purified water. The obtained eyewash was aseptically filled into a PET container. The osmotic pressure of this eye wash was 335 mOsm.
試験例
試験例１
検体として表１及び表２に示した実施例５〜１６及び比較例１〜１３の処方の点眼液を常法で作製して用いた。
点眼感の試験評価に健常者３名に対し、各検体の点眼液を各々２滴点眼し、点眼時のべたつき感、刺激感、清涼感をスコアー化した。各々評価項目につきスコアーを合算し、総合評価とした結果を表１及び表２に示した。
評価スコアー
＜べたつきのスコアー＞
スコアー０：べたつき感なし。
スコアー１：ほとんどべたつき感なし。
スコアー２：ややべたつき感あり。
スコアー３：べたつき感あり。
スコアー４：強いべたつき感あり。
＜刺激感のスコアー＞
スコアー０：刺激感なし。
スコアー１：ほとんど刺激感なし。
スコアー２：やや刺激感あり。
スコアー３：刺激感あり。
スコアー４：強い刺激感あり。
＜清涼感のスコアー＞
スコアー０：清涼感なし。
スコアー１：ほとんど清涼感なし。
スコアー２：やや清涼感あり。
スコアー３：清涼感あり。
スコアー４：強い清涼感あり。
総合評価
＜べたつき・刺激感の評価基準＞
◎：総スコアー ３以下
○：総スコアー ４〜６
△：総スコアー ７〜１０
×：総スコアー １０以上
＜清涼感の評価基準＞
◎：総スコアー １０以上
○：総スコアー ７〜１０
△：総スコアー ４〜６
×：総スコアー ３以下
Test example Test example 1
The ophthalmic solutions having the formulations of Examples 5 to 16 and Comparative Examples 1 to 13 shown in Tables 1 and 2 were prepared and used as samples.
For the test evaluation of eye drop, 3 drops of each eye drop were applied to 3 healthy subjects, and the stickiness, irritation, and coolness at the time of instillation were scored. Tables 1 and 2 show the results obtained by adding up the scores for the respective evaluation items to obtain a comprehensive evaluation.
Evaluation score <sticky score>
Score 0: No stickiness.
Score 1: Almost no stickiness.
Score 2: There is a slightly sticky feeling.
Score 3: There is a sticky feeling.
Score 4: Strong stickiness.
<Stimulation score>
Score 0: No irritation.
Score 1: Almost no irritation.
Score 2: Slightly irritating.
Score 3: There is a feeling of irritation.
Score 4: Strong irritation.
<Score of coolness>
Score 0: No refreshing feeling.
Score 1: Almost no refreshing feeling.
Score 2: Somewhat cool.
Score 3: There is a refreshing feeling.
Score 4: Strong refreshing feeling.
Comprehensive evaluation <Evaluation criteria for stickiness and irritation>
◎: Total score 3 or less ○: Total score 4-6
Δ: Total score 7-10
X: Total score of 10 or more <Evaluation criteria for coolness>
◎: Total score of 10 or more ○: Total score 7-10
Δ: Total score 4-6
×: Total score 3 or less
表１及び２において、HPMC：ヒドロキシプロピルメチルセルロースはメトローズ６０SH−４０００、メトローズ６０SH−１００００（信越化学工業（株）製）、 HEC：ヒドロキシエチルセルロースはCF-G（住友精化（株）製）、CVP：カルボキシビニルポリマーはカーボポール９８０NF（NOVEON・INC製）、PVP：ポリビニルピロリドンはK３０（和光純薬（株）製）、PVA：ポリビニルアルコールはゴーセノールEG−０５（日本合成化学（株）製）、MC：メチルセルロースはメトローズＳＭ−４００、メトローズＳＭ−４０００（信越化学工業（株）製）を用いた。 In Tables 1 and 2, HPMC: hydroxypropyl methylcellulose is Metrose 60SH-4000, Metrose 60SH-10000 (manufactured by Shin-Etsu Chemical Co., Ltd.), HEC: hydroxyethyl cellulose is CF-G (manufactured by Sumitomo Seika Co., Ltd.), CVP : Carbopol 980NF (manufactured by NOVEON INC), PVP: Polyvinylpyrrolidone K30 (manufactured by Wako Pure Chemical Industries, Ltd.), PVA: Polyvinyl alcohol is GOHSENOL EG-05 (manufactured by Nippon Synthetic Chemical Co., Ltd.), MC: Metrols SM-400 and Metrows SM-4000 (manufactured by Shin-Etsu Chemical Co., Ltd.) were used as methylcellulose.
比較例１〜３の結果から、水溶性高分子を配合する点眼剤において、エタノール、メントール、クロロブタノールの配合が無かった際、べたつき感、刺激感が生じ、良い点眼感が得られないことが示された。
比較例４、５の結果から、メントールの配合量が０．０４％を越えると、刺激感が強く生じることが示された。
比較例６、７の結果から、メントールの配合量が０．００４％以下であると、清涼感を持った点眼液が得られないことが示された。
実施例６と比較例８の結果から、メントールの配合量が０．００５％以上でべたつき感、刺激感が無く、清涼感のある本発明特有の効果が得られたことが示された。
実施例９と比較例１０，１１の結果から、粘度が１５mＰａ・ｓを越えると、水溶性高分子のべたつき感を改善できないことが示された。
実施例５〜１６より、点眼液の粘度が１．３〜１５mＰａ・ｓでべとつき・刺激の無い点眼液が得られることが示された。
From the results of Comparative Examples 1 to 3, in the ophthalmic solution containing the water-soluble polymer, when there was no blending of ethanol, menthol, and chlorobutanol, a sticky feeling and a irritating feeling were produced, and a good eye feeling could not be obtained. Indicated.
From the results of Comparative Examples 4 and 5, it was shown that when the blending amount of menthol exceeds 0.04%, a strong irritation is generated.
From the results of Comparative Examples 6 and 7, it was shown that an ophthalmic solution with a refreshing sensation could not be obtained when the amount of menthol was 0.004% or less.
From the results of Example 6 and Comparative Example 8, it was shown that when the blending amount of menthol was 0.005% or more, there was no stickiness or irritation, and the effect specific to the present invention with a refreshing feeling was obtained.
From the results of Example 9 and Comparative Examples 10 and 11, it was shown that when the viscosity exceeded 15 mPa · s, the stickiness of the water-soluble polymer could not be improved.
From Examples 5 to 16, it was shown that an ophthalmic solution without stickiness and irritation was obtained when the viscosity of the ophthalmic solution was 1.3 to 15 mPa · s.
本発明の眼科用剤は、眼のかわき、眼の疲労やドライアイの緩和に有用であり、使用時のべたつき感が改善され、刺激の無い使用感の良い点眼液、人工涙液、洗眼液として用いることができる。
The ophthalmic preparation of the present invention is useful for relieving eye irritation, eye fatigue and dry eye, has improved stickiness during use, and has good irritation without eye irritation, artificial tears, and eyewash Can be used as
Claims (3)
The ophthalmic agent according to claim 1, wherein the water-soluble polymer is hydroxypropylmethylcellulose.
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| WO2009001899A1 (en) * | 2007-06-26 | 2008-12-31 | Wakamoto Pharmaceutical Co., Ltd. | Aqueous composition |
| WO2011040432A1 (en) * | 2009-09-30 | 2011-04-07 | ロート製薬株式会社 | Eye wash agent |
| JP2014166976A (en) * | 2013-01-31 | 2014-09-11 | Rohto Pharmaceut Co Ltd | Eye drop |
| WO2015029717A1 (en) * | 2013-08-30 | 2015-03-05 | 日油株式会社 | Ophthalmic solution |
| WO2018199180A1 (en) * | 2017-04-25 | 2018-11-01 | わかもと製薬株式会社 | Thermogelling artificial tears |
| WO2020184479A1 (en) * | 2019-03-08 | 2020-09-17 | ロート製薬株式会社 | Ophthalmic composition having inhibited irritating sensation |
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| JP2004315517A (en) * | 2003-04-04 | 2004-11-11 | Rohto Pharmaceut Co Ltd | Ophthalmologic composition |
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| JP2002097129A (en) * | 2000-07-21 | 2002-04-02 | Rohto Pharmaceut Co Ltd | Eye lotion |
| JP2002154989A (en) * | 2000-11-14 | 2002-05-28 | Lion Corp | Ophthalmic composition and composition having improved retention of medicine in biological mucosa |
| JP2004315517A (en) * | 2003-04-04 | 2004-11-11 | Rohto Pharmaceut Co Ltd | Ophthalmologic composition |
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| WO2009001899A1 (en) * | 2007-06-26 | 2008-12-31 | Wakamoto Pharmaceutical Co., Ltd. | Aqueous composition |
| CN101784287B (en) * | 2007-06-26 | 2013-04-24 | 若素制药株式会社 | Aqueous composition |
| JP5340149B2 (en) * | 2007-06-26 | 2013-11-13 | わかもと製薬株式会社 | Aqueous composition |
| WO2011040432A1 (en) * | 2009-09-30 | 2011-04-07 | ロート製薬株式会社 | Eye wash agent |
| JP2011093889A (en) * | 2009-09-30 | 2011-05-12 | Rohto Pharmaceutical Co Ltd | Eye wash agent |
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| JP2014166976A (en) * | 2013-01-31 | 2014-09-11 | Rohto Pharmaceut Co Ltd | Eye drop |
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| JPWO2015029717A1 (en) * | 2013-08-30 | 2017-03-02 | 日油株式会社 | Eye drops |
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| AU2014313287B2 (en) * | 2013-08-30 | 2019-05-23 | Nof Corporation | Ophthalmic solution |
| US10471171B2 (en) | 2013-08-30 | 2019-11-12 | Nof Corporation | Ophthalmic solution |
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