JP2002080314A - Preservative - Google Patents
PreservativeInfo
- Publication number
- JP2002080314A JP2002080314A JP2001184171A JP2001184171A JP2002080314A JP 2002080314 A JP2002080314 A JP 2002080314A JP 2001184171 A JP2001184171 A JP 2001184171A JP 2001184171 A JP2001184171 A JP 2001184171A JP 2002080314 A JP2002080314 A JP 2002080314A
- Authority
- JP
- Japan
- Prior art keywords
- preservative
- weight
- acid
- present
- salt
- 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.)
- Granted
Links
- 230000002335 preservative effect Effects 0.000 title claims abstract description 38
- 239000003755 preservative agent Substances 0.000 title claims abstract description 31
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims abstract description 11
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims abstract description 11
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims abstract description 11
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims abstract description 9
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000004327 boric acid Substances 0.000 claims abstract description 9
- 229920000642 polymer Polymers 0.000 claims abstract description 9
- 150000003839 salts Chemical class 0.000 claims abstract description 9
- 229910021538 borax Inorganic materials 0.000 claims abstract description 8
- 239000004328 sodium tetraborate Substances 0.000 claims abstract description 8
- 235000010339 sodium tetraborate Nutrition 0.000 claims abstract description 8
- 239000003889 eye drop Substances 0.000 claims description 8
- 239000007788 liquid Substances 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 6
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 4
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 4
- 239000007864 aqueous solution Substances 0.000 claims description 3
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims 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 claims description 3
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 2
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 2
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 2
- 229920000609 methyl cellulose Polymers 0.000 claims description 2
- 239000001923 methylcellulose Substances 0.000 claims description 2
- 235000010981 methylcellulose Nutrition 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 3
- 239000000654 additive Substances 0.000 abstract description 2
- 238000004321 preservation Methods 0.000 abstract description 2
- 239000004615 ingredient Substances 0.000 abstract 1
- 239000012669 liquid formulation Substances 0.000 abstract 1
- 235000002639 sodium chloride Nutrition 0.000 description 8
- 230000002421 anti-septic effect Effects 0.000 description 7
- 229940012356 eye drops Drugs 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 229960001484 edetic acid Drugs 0.000 description 6
- 241000894006 Bacteria Species 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 229960000686 benzalkonium chloride Drugs 0.000 description 4
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 4
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 4
- 239000004334 sorbic acid Substances 0.000 description 4
- 235000010199 sorbic acid Nutrition 0.000 description 4
- 229940075582 sorbic acid Drugs 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 description 3
- 229960001950 benzethonium chloride Drugs 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 229920003023 plastic Polymers 0.000 description 3
- 239000004033 plastic Substances 0.000 description 3
- 239000002562 thickening agent Substances 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 229930003779 Vitamin B12 Natural products 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 230000000052 comparative effect Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000003204 osmotic effect Effects 0.000 description 2
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 239000012929 tonicity agent Substances 0.000 description 2
- 235000019163 vitamin B12 Nutrition 0.000 description 2
- 239000011715 vitamin B12 Substances 0.000 description 2
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 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
- 208000028006 Corneal injury Diseases 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 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
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-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
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 1
- BIVBRWYINDPWKA-VLQRKCJKSA-L Glycyrrhizinate dipotassium Chemical compound [K+].[K+].O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@H]1CC[C@]2(C)[C@H]3C(=O)C=C4[C@@H]5C[C@](C)(CC[C@@]5(CC[C@@]4(C)[C@]3(C)CC[C@H]2C1(C)C)C)C(O)=O)C([O-])=O)[C@@H]1O[C@H](C([O-])=O)[C@@H](O)[C@H](O)[C@H]1O BIVBRWYINDPWKA-VLQRKCJKSA-L 0.000 description 1
- 101000650817 Homo sapiens Semaphorin-4D Proteins 0.000 description 1
- 229930195725 Mannitol Natural products 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
- 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
- 102100027744 Semaphorin-4D Human genes 0.000 description 1
- 229920002385 Sodium hyaluronate Polymers 0.000 description 1
- 229930003471 Vitamin B2 Natural products 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229960002684 aminocaproic acid Drugs 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 239000000043 antiallergic agent Substances 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 229960004926 chlorobutanol Drugs 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
- 230000000295 complement effect Effects 0.000 description 1
- 239000000882 contact lens solution Substances 0.000 description 1
- 229960000265 cromoglicic acid Drugs 0.000 description 1
- 239000000850 decongestant Substances 0.000 description 1
- 229940124581 decongestants Drugs 0.000 description 1
- 229960000525 diphenhydramine hydrochloride Drugs 0.000 description 1
- 229940101029 dipotassium glycyrrhizinate Drugs 0.000 description 1
- IKALZAKZWHFNIC-JIZZDEOASA-L dipotassium;(2s)-2-aminobutanedioate Chemical compound [K+].[K+].[O-]C(=O)[C@@H](N)CC([O-])=O IKALZAKZWHFNIC-JIZZDEOASA-L 0.000 description 1
- VLARUOGDXDTHEH-UHFFFAOYSA-L disodium cromoglycate Chemical compound [Na+].[Na+].O1C(C([O-])=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C([O-])=O)O2 VLARUOGDXDTHEH-UHFFFAOYSA-L 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- -1 etc.) Substances 0.000 description 1
- 235000011187 glycerol Nutrition 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
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- TZBAVQKIEKDGFH-UHFFFAOYSA-N n-[2-(diethylamino)ethyl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound [Cl-].C1=CC=C2SC(C(=O)NCC[NH+](CC)CC)=CC2=C1 TZBAVQKIEKDGFH-UHFFFAOYSA-N 0.000 description 1
- 229960004760 naphazoline hydrochloride Drugs 0.000 description 1
- 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 1
- 229960002253 neostigmine methylsulfate Drugs 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 229940101267 panthenol Drugs 0.000 description 1
- 235000020957 pantothenol Nutrition 0.000 description 1
- 239000011619 pantothenol Substances 0.000 description 1
- 239000003186 pharmaceutical solution Substances 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 239000004302 potassium sorbate Substances 0.000 description 1
- 235000010241 potassium sorbate Nutrition 0.000 description 1
- 229940069338 potassium sorbate Drugs 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- RADKZDMFGJYCBB-UHFFFAOYSA-N pyridoxal hydrochloride Natural products CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 description 1
- 229960002477 riboflavin Drugs 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 229940037001 sodium edetate Drugs 0.000 description 1
- 229940010747 sodium hyaluronate Drugs 0.000 description 1
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 229960005404 sulfamethoxazole Drugs 0.000 description 1
- JLKIGFTWXXRPMT-UHFFFAOYSA-N sulphamethoxazole Chemical compound O1C(C)=CC(NS(=O)(=O)C=2C=CC(N)=CC=2)=N1 JLKIGFTWXXRPMT-UHFFFAOYSA-N 0.000 description 1
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 229940021790 tetrahydrozoline hydrochloride 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
- 239000011782 vitamin Substances 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000019164 vitamin B2 Nutrition 0.000 description 1
- 239000011716 vitamin B2 Substances 0.000 description 1
- 235000019158 vitamin B6 Nutrition 0.000 description 1
- 239000011726 vitamin B6 Substances 0.000 description 1
- 229940011671 vitamin b6 Drugs 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、ホウ酸、エチレン
ジアミン四酢酸およびポリビニルピロリドンの組み合わ
せからなる防腐剤、さらにはこれにセルロース系高分子
を併用してなる防腐剤に関し、点眼液、コンタクトレン
ズ用溶液などの水性液剤に好適に利用できる。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a preservative comprising a combination of boric acid, ethylenediaminetetraacetic acid and polyvinylpyrrolidone, and further to a preservative obtained by using a cellulose polymer in combination therewith. It can be suitably used for aqueous liquids such as solutions.
【０００２】[0002]
【従来の技術】従来より、点眼液やコンタクトレンズ用
溶液の防腐剤として、塩化ベンザルコニウム、塩化ベン
ゼトニウム、ソルビン酸等が用いられている。2. Description of the Related Art Conventionally, benzalkonium chloride, benzethonium chloride, sorbic acid and the like have been used as preservatives for eye drops and contact lens solutions.
【０００３】[0003]
【発明が解決しようとする課題】しかし、塩化ベンザル
コニウムや塩化ベンゼトニウムは、防腐効果は高いもの
の濃度によっては角膜障害を引き起こす可能性もあり、
使用濃度に制約がある。さらに、これらはコンタクトレ
ンズやプラスチック容器に吸着しやすい性質もある。However, benzalkonium chloride and benzethonium chloride have a high preservative effect, but may cause corneal damage depending on their concentration.
There are restrictions on the concentration used. Furthermore, they also have the property of easily adsorbing to contact lenses and plastic containers.
【０００４】また、コンタクトレンズ用の点眼液の防腐
剤として汎用されているソルビン酸は、副作用が少なく
コンタクトレンズやプラスチック容器への吸着も少ない
ものの防腐効果が弱いという問題がある。[0004] Sorbic acid, which is widely used as an antiseptic for eye drops for contact lenses, has a problem that the antiseptic effect is weak, though it has few side effects and little adsorption to contact lenses and plastic containers.
【０００５】一方、防腐剤として点眼液等の医薬品に使
用できる成分には限りがある。[0005] On the other hand, components that can be used as preservatives in pharmaceuticals such as eye drops are limited.
【０００６】[0006]
【課題を解決するための手段】そこで本発明者らは点眼
液等の水性製剤に既に使用されている成分を組み合わせ
て防腐効果を発揮させるべく鋭意研究を行った。点眼液
においてホウ酸および/またはホウ砂は緩衝剤として、
また、エチレンジアミン四酢酸またはその塩は安定化剤
としてそれぞれ広く用いられており、これらの化合物は
弱いながらも防腐作用を持ち合わせていることに着目
し、その防腐効果を高める研究を行った。その結果、
（Ａ）ホウ酸および/またはホウ砂、および（Ｂ）エチ
レンジアミン四酢酸に、増粘剤として汎用されている
（Ｃ）ポリビニルピロリドンを添加すれば顕著に防腐効
果が高められることを見いだし、本発明を完成するに至
った。また、この組み合わせに、やはり増粘剤として汎
用されているセルロース系高分子を添加すれば防腐効果
がさらに増強されることも併せて見いだした。The inventors of the present invention have conducted intensive studies to combine the components already used in aqueous preparations such as eye drops and the like to exert an antiseptic effect. Boric acid and / or borax as a buffer in eye drops,
In addition, ethylenediaminetetraacetic acid or a salt thereof has been widely used as a stabilizer, and attention has been paid to the fact that these compounds have a preservative effect although they are weak, and a study for enhancing the preservative effect was conducted. as a result,
It has been found that the addition of (C) polyvinylpyrrolidone, which is widely used as a thickener, to (A) boric acid and / or borax and (B) ethylenediaminetetraacetic acid can significantly enhance the preservative effect. Was completed. It was also found that the addition of a cellulosic polymer, which is also commonly used as a thickener, to this combination further enhances the preservative effect.
【０００７】[0007]
【発明の実施の形態】本発明の防腐剤は、三つの必須成
分から構成され、その第一の成分は、ホウ酸および／ま
たはホウ砂である。ホウ酸および／またはホウ砂の添加
量の好ましい範囲は０．０５〜３．０重量％、さらに好
ましい範囲は０．５〜２．０重量％である。上記第一成
分の配合量が少なすぎると十分な防腐効果が得られず、
多すぎると眼に対する安全性の点から好ましくない。DETAILED DESCRIPTION OF THE INVENTION The preservative of the present invention is composed of three essential components, the first of which is boric acid and / or borax. The preferred range of the amount of boric acid and / or borax is 0.05 to 3.0% by weight, and the more preferred range is 0.5 to 2.0% by weight. If the amount of the first component is too small, a sufficient preservative effect cannot be obtained,
If it is too large, it is not preferable from the viewpoint of safety for eyes.
【０００８】本発明の第二の成分は、エチレンジアミン
四酢酸またはその塩であり、塩としては四ナトリウム
塩、二ナトリウム塩（エデト酸ナトリウム）が好適に使
用できる。エチレンジアミン四酢酸またはその塩の添加
量の好ましい範囲は０．０１〜０．３重量％、さらに好
ましい範囲は０．０５〜０．２重量％である。上記第二
成分の配合量が少なすぎると十分な安定性および防腐効
果が得られず、多すぎると眼に対する安全性の点から好
ましくない。The second component of the present invention is ethylenediaminetetraacetic acid or a salt thereof. As the salt, a tetrasodium salt or a disodium salt (sodium edetate) can be suitably used. A preferred range of the amount of ethylenediaminetetraacetic acid or a salt thereof added is 0.01 to 0.3% by weight, and a more preferable range is 0.05 to 0.2% by weight. If the amount of the second component is too small, sufficient stability and preservative effect cannot be obtained, and if it is too large, it is not preferable from the viewpoint of safety for eyes.
【０００９】本発明の第三の成分は、ポリビニルピロリ
ドン（ＰＶＰ）であり、例えば「ＰＶＰ Ｋ-２５」
（平均分子量 ２５，０００）、「ＰＶＰ Ｋ-３０」
（平均分子量 ４０，０００）、「ＰＶＰ Ｋ-９０」
（平均分子量 ３６０，０００）などを使用できる。Ｐ
ＶＰの添加量の好ましい範囲は０．０２〜４．０重量
％、さらに好ましい範囲は０．1〜２．０重量％であ
る。上記第三成分の配合量が少なすぎると十分な防腐効
果が得られず、多すぎると不快な粘つき感を伴い好まし
くない。The third component of the present invention is polyvinylpyrrolidone (PVP), for example, "PVP K-25"
(Average molecular weight 25,000), "PVP K-30"
(Average molecular weight 40,000), "PVP K-90"
(Average molecular weight 360,000) can be used. P
The preferred range of the amount of VP added is 0.02 to 4.0% by weight, and the more preferred range is 0.1 to 2.0% by weight. If the amount of the third component is too small, a sufficient antiseptic effect cannot be obtained. If the amount is too large, unpleasant stickiness is undesirably caused.
【００１０】本発明では、上記第一〜三の成分に加え
て、セルロース系高分子を添加すると防腐効果がさらに
増強される。セルロース系高分子の例としては、ヒドロ
キシプロピルメチルセルロース、ヒドロキシプロピルセ
ルロース、メチルセルロース、ヒドロキシエチルセルロ
ース等が挙げられるが、ヒドロキシプロピルメチルセル
ロースが特に好適である。セルロース系高分子の添加量
は、特に制限されないが、好ましい範囲は０．０１〜
０．５重量％、さらに好ましい範囲は０．０５〜０．３
重量％である。In the present invention, the addition of a cellulosic polymer in addition to the first to third components further enhances the preservative effect. Examples of the cellulosic polymer include hydroxypropylmethylcellulose, hydroxypropylcellulose, methylcellulose, hydroxyethylcellulose and the like, with hydroxypropylmethylcellulose being particularly preferred. The addition amount of the cellulosic polymer is not particularly limited, but the preferred range is 0.01 to
0.5% by weight, more preferably 0.05 to 0.3
% By weight.
【００１１】本発明の防腐剤は、人体に対する安全性も
高く、コンタクトレンズやプラスチック用容器への吸着
も少ないので、点眼液、コンタクトレンズ用溶液等の医
薬用の水性液剤に好適に用いられる。これらの水性液剤
を調製するには、上記の成分以外に、他の添加成分とし
て、等張化剤、pH調節剤、可溶化剤、保存剤等を適宜配
合することができる。Since the preservative of the present invention has high safety to the human body and little adsorption to contact lenses and plastic containers, it is suitably used for aqueous pharmaceutical solutions such as eye drops and solution for contact lenses. In preparing these aqueous liquid preparations, in addition to the above-mentioned components, other additives such as a tonicity agent, a pH regulator, a solubilizer, and a preservative can be appropriately compounded.
【００１２】この水性液剤を応用することができる薬物
としては、特に制限されないが、例えば各種のビタミン
類（ビタミンB2、ビタミンB6、ビタミンB12、ビタミン
E、パンテノール等）、充血除去剤（塩酸テトラヒドロ
ゾリン、塩酸ナファゾリン等）、抗炎症剤（グリチルリ
チン酸二カリウム、イプシロン-アミノカプロン酸
等）、抗ヒスタミン剤（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）、抗アレルギー剤（ク
ロモグリク酸ナトリウム等）、抗菌剤（スルファメトキ
サゾール等）、 アミノ酸類（Ｌ−アスパラギン酸カリ
ウム、アミノエチルスルホン酸、コンドロイチン硫酸ナ
トリウム等）、ヒアルロン酸ナトリウム、メチル硫酸ネ
オスチグミン等を挙げることができる。The drug to which the aqueous solution can be applied is not particularly limited. For example, various kinds of vitamins (vitamin B2, vitamin B6, vitamin B12, vitamin B12)
E, panthenol, etc.), decongestants (tetrahydrozoline hydrochloride, naphazoline hydrochloride, etc.), anti-inflammatory agents (dipotassium glycyrrhizinate, epsilon-aminocaproic acid, etc.), antihistamines (chlorpheniramine maleate, diphenhydramine hydrochloride, etc.), anti-allergy Agents (eg, sodium cromoglycate), antibacterial agents (eg, sulfamethoxazole), amino acids (eg, potassium L-aspartate, aminoethylsulfonic acid, sodium chondroitin sulfate), sodium hyaluronate, and neostigmine methyl sulfate. Can be.
【００１３】等張化剤としては、例えばグリセリン、プ
ロピレングリコール、塩化ナトリウム、塩化カリウム、
ソルビトール、マンニトール等を挙げることができる。Examples of the tonicity agent include glycerin, propylene glycol, sodium chloride, potassium chloride,
Sorbitol, mannitol and the like can be mentioned.
【００１４】pH調節剤としては、例えば塩酸、クエン
酸、リン酸、酢酸、水酸化ナトリウム、水酸化カリウ
ム、炭酸ナトリウム、炭酸水素ナトリウム等を挙げるこ
とができる。Examples of the pH adjuster include hydrochloric acid, citric acid, phosphoric acid, acetic acid, sodium hydroxide, potassium hydroxide, sodium carbonate, sodium hydrogen carbonate and the like.
【００１５】可溶化剤としては、例えばポリソルベート
８０、ポリエキシエチレン硬化ヒマシ油６０、マクロゴ
ール４０００等を挙げることができる。Examples of the solubilizing agent include polysorbate 80, polyexylene ethylene-hardened castor oil 60, Macrogol 4000 and the like.
【００１６】本発明の防腐剤は、汎用されているソルビ
ン酸、ソルビン酸カリウム、塩化ベンザルコニウム、塩
化ベンゼトニウム、パラオキシ安息香酸メチル、パラオ
キシ安息香酸プロピル、クロロブタノール等の防腐剤と
併用することができる。この場合、本発明の防腐剤は汎
用防腐剤の防腐効果を補完することができるので、汎用
防腐剤の使用量を大幅に減少できる効果も有する。The preservative of the present invention can be used in combination with commonly used preservatives such as sorbic acid, potassium sorbate, benzalkonium chloride, benzethonium chloride, methyl parahydroxybenzoate, propyl paraoxybenzoate and chlorobutanol. it can. In this case, since the preservative of the present invention can complement the preservative effect of the general-purpose preservative, it also has the effect of greatly reducing the amount of the general-purpose preservative used.
【００１７】本発明の液剤を点眼液として使用する場合
は、ｐＨは７．０付近に調節することが望ましく、浸透
圧比は１．０付近に調節することが望ましい。When the liquid preparation of the present invention is used as eye drops, it is desirable to adjust the pH to around 7.0 and the osmotic pressure ratio to around 1.0.
【００１８】以下に、実施例を挙げて本発明を詳しく説
明するが、これは本発明の範囲を限定するものではな
い。Hereinafter, the present invention will be described in detail with reference to examples, but this does not limit the scope of the present invention.
【００１９】[0019]
【実施例】本発明の防腐剤の防腐効果を調べるため、以
下に従い保存効力試験を行った。EXAMPLES In order to examine the preservative effect of the preservative of the present invention, a preservative efficacy test was performed as follows.
【００２０】（保存効力試験）常法により蒸留水に表１
の実施例１〜４および比較例1〜3に示す配合成分を加え
て液剤を調製した。また、各液剤には等張化剤として塩
化ナトリウムを添加し、浸透圧を１．０に調整し、さら
に、必要に応じて水酸化ナトリウムを加えてｐＨを７．
０に調節した。保存効力試験は、第十三改正日本薬局方
の保存効力試験法に準拠して行った。本試験では、試験
菌として、Staphyrococcus aureus(S.aureus)を用い
て、下記の計算式に従い菌の生存率を算出した。得られ
た値を表１に示す。(Preservation Efficacy Test) Table 1
The liquid components were prepared by adding the components shown in Examples 1 to 4 and Comparative Examples 1 to 3. Further, sodium chloride is added to each liquid as an isotonic agent, the osmotic pressure is adjusted to 1.0, and if necessary, sodium hydroxide is added to adjust the pH to 7.0.
Adjusted to zero. The preservative efficacy test was performed in accordance with the preservative efficacy test method of the 13th revised Japanese Pharmacopoeia. In this test, Staphyrococcus aureus (S. aureus) was used as a test bacterium, and the survival rate of the bacterium was calculated according to the following formula. Table 1 shows the obtained values.
【００２１】生存率(％)=２週間後の菌数／初期菌数×
１００Survival rate (%) = number of bacteria after 2 weeks / initial number of bacteria ×
100
【００２２】[0022]
【表１】 [Table 1]
【００２３】[0023]
【００２４】[0024]
【発明の効果】表１から明らかなように、本発明の実施
例１および２では、比較例１〜３に比べて、防腐効果が
顕著に向上している。更にHPMCを加えた実施例３および
４では実施例１および２よりも防腐効果が向上してい
る。このように、（Ａ）ホウ酸および/またはホウ砂、
（Ｂ）エチレンジアミン四酢酸またはその塩に加えて、
（Ｃ）ポリビニルピロリドンを配合する本発明の防腐剤
は、各成分が相乗的に作用してその防腐力を高めるもの
である。また、さらにこれにセルロース系高分子を配合
すれば、本発明の防腐効果を一層高めることができる。
従って、本発明の防腐剤は、緩衝剤、安定剤、増粘剤と
して汎用されている化合物を組み合わせて、液剤の防腐
効果を高めるものであるので、人体に対する安全性も高
く、医薬用途に適する。また本発明の防腐剤により、汎
用されている塩化ベンザルコニウム、ソルビン酸等の防
腐剤と併用することもでき、その場合汎用防腐剤の添加
量を減らすことができる。As is clear from Table 1, in Examples 1 and 2 of the present invention, the antiseptic effect is remarkably improved as compared with Comparative Examples 1 to 3. Further, in Examples 3 and 4 to which HPMC was added, the antiseptic effect was improved as compared with Examples 1 and 2. Thus, (A) boric acid and / or borax,
(B) In addition to ethylenediaminetetraacetic acid or a salt thereof,
In the preservative of the present invention containing (C) polyvinylpyrrolidone, each component acts synergistically to increase the preservative power. Further, if a cellulosic polymer is further added thereto, the antiseptic effect of the present invention can be further enhanced.
Therefore, the preservative of the present invention enhances the preservative effect of the liquid preparation by combining a compound widely used as a buffer, a stabilizer, and a thickener, so that it is highly safe for the human body and is suitable for pharmaceutical use. . Further, the preservative of the present invention can be used in combination with preservatives such as benzalkonium chloride and sorbic acid which are widely used, and in this case, the amount of the general-purpose preservative can be reduced.
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.7 識別記号 ＦＩ テーマコート゛(参考） Ａ６１Ｋ 47/32 Ａ６１Ｋ 47/32 47/38 47/38 Ｆターム(参考） 4C076 AA12 BB24 DD22 DD49 EE16 EE32 FF39 4H011 AA02 BA02 BB06 BB09 BB18 BC19 DA13 DC05 DF04 DH10──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. 7 Identification symbol FI theme coat ゛ (reference) A61K 47/32 A61K 47/32 47/38 47/38 F term (reference) 4C076 AA12 BB24 DD22 DD49 EE16 EE32 FF39 4H011 AA02 BA02 BB06 BB09 BB18 BC19 DA13 DC05 DF04 DH10
Claims (7)
エチレンジアミン四酢酸またはその塩および（Ｃ）ポリ
ビニルピロリドンの組み合わせからなる防腐剤。(A) boric acid and / or borax, (B)
A preservative comprising a combination of ethylenediaminetetraacetic acid or a salt thereof and (C) polyvinylpyrrolidone.
することを特徴とする請求項１記載の防腐剤。2. The preservative according to claim 1, further comprising (D) a cellulosic polymer.
た水性液剤。3. An aqueous solution containing the preservative according to claim 1 or 2.
ウ砂０．０５〜３．０重量％、（Ｂ）エチレンジアミン
四酢酸またはその塩０．０１〜０．３重量％および
（Ｃ）ポリビニルピロリドン０．０２〜４．０重量％を
含有してなる水性液剤。5. A preservative comprising (A) 0.05 to 3.0% by weight of boric acid and / or borax, (B) 0.01 to 0.3% by weight of ethylenediaminetetraacetic acid or a salt thereof, and (C) Aqueous solution containing 0.02 to 4.0% by weight of polyvinylpyrrolidone.
１〜０．５重量％を含有してなる請求項５記載の水性液
剤。6. The method according to claim 1, further comprising:
The aqueous liquid preparation according to claim 5, comprising 1 to 0.5% by weight.
メチルセルロース、ヒドロキシプロピルセルロース、メ
チルセルロースまたはヒドロキシエチルセルロースであ
る請求項２の防腐剤または請求項６記載の水性液剤。7. The preservative according to claim 2, wherein the cellulosic polymer is hydroxypropylmethylcellulose, hydroxypropylcellulose, methylcellulose or hydroxyethylcellulose.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2001184171A JP4325129B2 (en) | 2000-06-19 | 2001-06-19 | Preservative |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2000182624 | 2000-06-19 | ||
| JP2000-182624 | 2000-06-19 | ||
| JP2001184171A JP4325129B2 (en) | 2000-06-19 | 2001-06-19 | Preservative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2002080314A true JP2002080314A (en) | 2002-03-19 |
| JP4325129B2 JP4325129B2 (en) | 2009-09-02 |
Family
ID=26594162
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2001184171A Expired - Lifetime JP4325129B2 (en) | 2000-06-19 | 2001-06-19 | Preservative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP4325129B2 (en) |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005162747A (en) * | 2003-11-12 | 2005-06-23 | Rohto Pharmaceut Co Ltd | Ophthalmic composition |
| JP2006230612A (en) * | 2005-02-23 | 2006-09-07 | Fukuyoo:Kk | Cleaning sheet |
| KR100644452B1 (en) | 2004-07-20 | 2006-11-10 | 서인범 | Fluid preservatives |
| WO2010113692A1 (en) * | 2009-03-30 | 2010-10-07 | 花王株式会社 | Method for enhancing efficacy of agrichemical, and agrichemical-containing composition |
| JP2012224872A (en) * | 2012-08-23 | 2012-11-15 | Kobayashi Pharmaceutical Co Ltd | Stabilizing agent for composition that contains water-soluble polymeric thickener |
| WO2016199854A1 (en) * | 2015-06-10 | 2016-12-15 | 参天製薬株式会社 | Ophthalmic solution and method for maintaining preservative efficacy of ophthalmic solution |
| WO2019176947A1 (en) * | 2018-03-13 | 2019-09-19 | 参天製薬株式会社 | Pollen bursting-inhibiting composition |
| JP2022017344A (en) * | 2018-03-13 | 2022-01-25 | 参天製薬株式会社 | Eyedrop-type eyewash composition |
| WO2023195543A1 (en) * | 2022-04-08 | 2023-10-12 | 東亜薬品株式会社 | Ophthalmic aqueous composition and method for imparting antiseptic effect |
-
2001
- 2001-06-19 JP JP2001184171A patent/JP4325129B2/en not_active Expired - Lifetime
Cited By (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005162747A (en) * | 2003-11-12 | 2005-06-23 | Rohto Pharmaceut Co Ltd | Ophthalmic composition |
| KR100644452B1 (en) | 2004-07-20 | 2006-11-10 | 서인범 | Fluid preservatives |
| JP2006230612A (en) * | 2005-02-23 | 2006-09-07 | Fukuyoo:Kk | Cleaning sheet |
| WO2010113692A1 (en) * | 2009-03-30 | 2010-10-07 | 花王株式会社 | Method for enhancing efficacy of agrichemical, and agrichemical-containing composition |
| JP2010235455A (en) * | 2009-03-30 | 2010-10-21 | Kao Corp | Agrochemical-containing composition |
| US9161530B2 (en) | 2009-03-30 | 2015-10-20 | Kao Corporation | Method for enhancing efficacy of agrichemical, and agrichemical-containing composition |
| US9572341B2 (en) | 2009-03-30 | 2017-02-21 | Kao Corporation | Method for enhancing efficacy of agrichemical, and agrichemical-containing composition |
| JP2012224872A (en) * | 2012-08-23 | 2012-11-15 | Kobayashi Pharmaceutical Co Ltd | Stabilizing agent for composition that contains water-soluble polymeric thickener |
| JP2017002042A (en) * | 2015-06-10 | 2017-01-05 | 参天製薬株式会社 | Eye drop, and method for maintaining eye drop antiseptic effect |
| WO2016199854A1 (en) * | 2015-06-10 | 2016-12-15 | 参天製薬株式会社 | Ophthalmic solution and method for maintaining preservative efficacy of ophthalmic solution |
| WO2019176947A1 (en) * | 2018-03-13 | 2019-09-19 | 参天製薬株式会社 | Pollen bursting-inhibiting composition |
| JPWO2019176947A1 (en) * | 2018-03-13 | 2021-03-18 | 参天製薬株式会社 | Composition for suppressing pollen rupture |
| JP2022017344A (en) * | 2018-03-13 | 2022-01-25 | 参天製薬株式会社 | Eyedrop-type eyewash composition |
| JP2022017345A (en) * | 2018-03-13 | 2022-01-25 | 参天製薬株式会社 | Eye drop type medicated composition |
| JP7303792B2 (en) | 2018-03-13 | 2023-07-05 | 参天製薬株式会社 | Pollen burst suppressing composition |
| CN116440156A (en) * | 2018-03-13 | 2023-07-18 | 参天制药株式会社 | Composition for inhibiting pollen rupture |
| WO2023195543A1 (en) * | 2022-04-08 | 2023-10-12 | 東亜薬品株式会社 | Ophthalmic aqueous composition and method for imparting antiseptic effect |
Also Published As
| Publication number | Publication date |
|---|---|
| JP4325129B2 (en) | 2009-09-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP3090125B2 (en) | Ophthalmic composition for soft contact lens, method for enhancing wettability of soft contact lens, and method for suppressing adsorption of terpenoid | |
| JP2003183157A (en) | Ophthalmic composition | |
| JP2001187728A (en) | Ophthalmic composition | |
| JP2002003364A (en) | Ophthalmic solution, ophthalmic composition and adsorption suppression method | |
| JP3142842B1 (en) | Ophthalmic composition and method for suppressing adsorption to soft contact lens | |
| JP5729109B2 (en) | Ophthalmic composition for soft contact lenses | |
| JPH1160505A (en) | Antiseptic composition | |
| JP7139500B2 (en) | ophthalmic composition | |
| JP2002356420A (en) | Stable aqueous solution | |
| JP2001318350A (en) | Solution for contact lenses | |
| JP4409798B2 (en) | Washing soap | |
| JP4325129B2 (en) | Preservative | |
| JP2003002837A (en) | Aqueous external preparation composition and method for preventing clouding of liquid composition | |
| CA2413088C (en) | Preservative | |
| JPH06293639A (en) | Stable vitamin A and vitamin E solubilized eye drops | |
| JP2003128583A (en) | Refreshing composition | |
| JP4801300B2 (en) | Liquid composition for external use | |
| JP5513702B2 (en) | Antibacterial eye drops | |
| JP2002020320A (en) | Antiseptic agent for eye drop | |
| JP2003128585A (en) | Composition for external use | |
| JP4442118B2 (en) | Stable eye drops | |
| JP2003095952A (en) | Ophthalmic composition and method for enhancing antimicrobial activity of the composition | |
| JP2893807B2 (en) | Azulene derivative-containing solution | |
| JP4524538B2 (en) | Ophthalmic composition | |
| JP2004339104A (en) | Method for solution stabilization |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20050223 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20050802 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20060523 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20060724 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20060907 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20060914 |
|
| A912 | Re-examination (zenchi) completed and case transferred to appeal board |
Free format text: JAPANESE INTERMEDIATE CODE: A912 Effective date: 20061006 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20090327 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20090601 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20120619 Year of fee payment: 3 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 Ref document number: 4325129 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20130619 Year of fee payment: 4 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| EXPY | Cancellation because of completion of term |