JP5785353B2 - Ophthalmic agent - Google Patents
Ophthalmic agent Download PDFInfo
- Publication number
- JP5785353B2 JP5785353B2 JP2004054694A JP2004054694A JP5785353B2 JP 5785353 B2 JP5785353 B2 JP 5785353B2 JP 2004054694 A JP2004054694 A JP 2004054694A JP 2004054694 A JP2004054694 A JP 2004054694A JP 5785353 B2 JP5785353 B2 JP 5785353B2
- Authority
- JP
- Japan
- Prior art keywords
- ophthalmic
- acid
- pranoprofen
- sodium
- present
- 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.)
- Expired - Lifetime
Links
- 239000003732 agents acting on the eye Substances 0.000 title claims description 16
- 229940125702 ophthalmic agent Drugs 0.000 title claims description 16
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 31
- TVQZAMVBTVNYLA-UHFFFAOYSA-N Pranoprofen Chemical compound C1=CC=C2CC3=CC(C(C(O)=O)C)=CC=C3OC2=N1 TVQZAMVBTVNYLA-UHFFFAOYSA-N 0.000 claims description 21
- 229960003101 pranoprofen Drugs 0.000 claims description 20
- 238000002360 preparation method Methods 0.000 claims description 15
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical class OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 14
- 229960000265 cromoglicic acid Drugs 0.000 claims description 13
- 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 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 13
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical group [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 claims description 9
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 claims description 5
- 239000004334 sorbic acid Substances 0.000 claims description 5
- 235000010199 sorbic acid Nutrition 0.000 claims description 5
- 229940075582 sorbic acid Drugs 0.000 claims description 5
- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 claims description 4
- 229910021538 borax Inorganic materials 0.000 claims description 4
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 claims description 4
- 229940009662 edetate Drugs 0.000 claims description 4
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims description 4
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 4
- 229920000053 polysorbate 80 Polymers 0.000 claims description 4
- 239000004328 sodium tetraborate Substances 0.000 claims description 4
- 235000010339 sodium tetraborate Nutrition 0.000 claims description 3
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 claims description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 2
- 239000002563 ionic surfactant Substances 0.000 claims 1
- 235000002639 sodium chloride Nutrition 0.000 description 16
- 230000000052 comparative effect Effects 0.000 description 11
- 239000003889 eye drop Substances 0.000 description 6
- -1 edetate salts Chemical class 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 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
- 230000003110 anti-inflammatory effect Effects 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 4
- 239000002736 nonionic surfactant Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-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
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 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
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229960000686 benzalkonium chloride Drugs 0.000 description 2
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 2
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 2
- 239000004327 boric acid Substances 0.000 description 2
- 239000003795 chemical substances by application 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
- 229940109248 cromoglycate Drugs 0.000 description 2
- IMZMKUWMOSJXDT-UHFFFAOYSA-N cromoglycic acid Chemical compound O1C(C(O)=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C(O)=O)O2 IMZMKUWMOSJXDT-UHFFFAOYSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 229940048820 edetates Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229940012356 eye drops Drugs 0.000 description 2
- 229960000905 indomethacin Drugs 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 239000007951 isotonicity adjuster Substances 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000003002 pH adjusting agent Substances 0.000 description 2
- 229940068968 polysorbate 80 Drugs 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 235000019260 propionic acid Nutrition 0.000 description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- 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 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000003637 steroidlike Effects 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- 230000004102 tricarboxylic acid cycle Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 0 CC1=CCC(*)C2=C1OC(*)=CC2=* Chemical compound CC1=CCC(*)C2=C1OC(*)=CC2=* 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 244000183685 Citrus aurantium Species 0.000 description 1
- 235000007716 Citrus aurantium Nutrition 0.000 description 1
- 240000004307 Citrus medica Species 0.000 description 1
- 241001672694 Citrus reticulata Species 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
- 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
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-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
- 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 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 1
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 1
- 206010039085 Rhinitis allergic Diseases 0.000 description 1
- 239000004288 Sodium dehydroacetate Substances 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- GZLGNNHEHXBCBI-UHFFFAOYSA-L [Na+].[Na+].OC(=O)C(O)C(O)C(O)=O.[O-]C(=O)C(O)C(O)C([O-])=O Chemical compound [Na+].[Na+].OC(=O)C(O)C(O)C(O)=O.[O-]C(=O)C(O)C(O)C([O-])=O GZLGNNHEHXBCBI-UHFFFAOYSA-L 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 201000010105 allergic rhinitis Diseases 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
- 230000036592 analgesia Effects 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 239000000730 antalgic 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
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 229960001950 benzethonium chloride Drugs 0.000 description 1
- 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 1
- 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 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 229960001927 cetylpyridinium chloride Drugs 0.000 description 1
- YMKDRGPMQRFJGP-UHFFFAOYSA-M cetylpyridinium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+]1=CC=CC=C1 YMKDRGPMQRFJGP-UHFFFAOYSA-M 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- KFGJICJPSZZEEP-UHFFFAOYSA-L dipotassium;hydrogen phosphate;hydrate Chemical compound O.[K+].[K+].OP([O-])([O-])=O KFGJICJPSZZEEP-UHFFFAOYSA-L 0.000 description 1
- PXEDJBXQKAGXNJ-QTNFYWBSSA-L disodium L-glutamate Chemical compound [Na+].[Na+].[O-]C(=O)[C@@H](N)CCC([O-])=O PXEDJBXQKAGXNJ-QTNFYWBSSA-L 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 229960001484 edetic acid Drugs 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 229940071106 ethylenediaminetetraacetate Drugs 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose 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
- 229960001340 histamine Drugs 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 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 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 206010023332 keratitis Diseases 0.000 description 1
- 201000010666 keratoconjunctivitis Diseases 0.000 description 1
- 239000002075 main ingredient Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 235000013923 monosodium glutamate Nutrition 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 239000002997 ophthalmic solution Substances 0.000 description 1
- 229940054534 ophthalmic solution Drugs 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 238000001782 photodegradation Methods 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000019259 sodium dehydroacetate Nutrition 0.000 description 1
- 229940079839 sodium dehydroacetate Drugs 0.000 description 1
- 229940073490 sodium glutamate Drugs 0.000 description 1
- DSOWAKKSGYUMTF-GZOLSCHFSA-M sodium;(1e)-1-(6-methyl-2,4-dioxopyran-3-ylidene)ethanolate Chemical compound [Na+].C\C([O-])=C1/C(=O)OC(C)=CC1=O DSOWAKKSGYUMTF-GZOLSCHFSA-M 0.000 description 1
- 235000014214 soft drink Nutrition 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 239000004753 textile Substances 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- LEAHFJQFYSDGGP-UHFFFAOYSA-K trisodium;dihydrogen phosphate;hydrogen phosphate Chemical compound [Na+].[Na+].[Na+].OP(O)([O-])=O.OP([O-])([O-])=O LEAHFJQFYSDGGP-UHFFFAOYSA-K 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
Description
本発明は、プラノプロフェン及びクロモグリク酸ナトリウムを含有する眼科用剤に関し、更に詳しくはエデト酸塩類及びクエン酸又はその塩を含有する眼科用剤に関する。 The present invention relates to an ophthalmic agent containing pranoprofen and sodium cromoglycate, and more particularly to an ophthalmic agent containing edetate salts and citric acid or a salt thereof.
プラノプロフェンはプロピオン酸系の酸性非ステロイド系抗炎症化合物であり、眼科用としては外眼部及び前眼部における角結膜炎等の炎症疾患に対して有用で、点眼剤の形態で実用に供されている。例えば、クロモグリク酸を配合することによってプラノプロフェンの抗炎症作用を増強させる方法（特許文献１参照）が提案されている。 Planoprofen is a propionic acid-based acidic non-steroidal anti-inflammatory compound that is useful for ophthalmic use against inflammatory diseases such as keratoconjunctivitis in the external and anterior segments and is practically used in the form of eye drops. Has been. For example, a method for enhancing the anti-inflammatory action of pranoprofen by blending cromoglycic acid (see Patent Document 1) has been proposed.
また、プラノプロフェンは水溶液状態では、不安定であり、特に光に対しては長期保存中に徐々に分解されてしまうという問題がある。この光安定性の低さを改善するために種々の試みがなされている。例えば、酸化防止剤を配合する方法（特許文献２参照）や、サルファ剤を配合し光劣化を抑制する方法（特許文献３参照）や、容器を遮光容器にする方法（非特許文献１参照）等が提案されている。
特許文献１に記載の発明はプラノプロフェンの抗炎症効果を増強することができるが、プラノプロフェンの安定性については言及されていない。 The invention described in Patent Document 1 can enhance the anti-inflammatory effect of pranoprofen, but does not mention the stability of pranoprofen.
本発明者らによる研究の結果、クロモグリク酸を配合することによって、プラノプロフェンの安定性を高め、光劣化による沈殿を抑制する効果があることがわかった。しかし、クロモグリク酸のみでは十分な安定性を確保することができず、光により着色してしまうという知見も得られている。 As a result of studies by the present inventors, it has been found that the incorporation of cromoglycic acid has the effect of increasing the stability of pranoprofen and suppressing precipitation due to photodegradation. However, it has been found that sufficient stability cannot be ensured with cromoglycic acid alone, and it is colored by light.
本発明は以上のような課題に鑑みてなされたものであり、プラノプロフェンを含有した眼科用剤において、プラノプロフェンをより安定な状態で存在させることが可能な眼科用剤を提供することを目的とする。 The present invention has been made in view of the problems as described above, and provides an ophthalmic agent capable of allowing pranoprofen to exist in a more stable state in an ophthalmic agent containing pranoprofen. With the goal.
より具体的には、本発明は以下のようなものを提供する。 More specifically, the present invention provides the following.
（１） ａ）プラノプロフェン０．００５Ｗ／Ｖ％から０．２Ｗ／Ｖ％、ｂ）クロモグリク酸ナトリウム０．０５Ｗ／Ｖ％から３．０Ｗ／Ｖ％、並びにｃ）エデト酸塩類０．０００１Ｗ／Ｖ％から０．１５Ｗ／Ｖ％、クエン酸０．００５Ｗ／Ｖ％から１．０Ｗ／Ｖ％、及びクエン酸塩０．００５Ｗ／Ｖ％から１．０Ｗ／Ｖ％、からなる群から選ばれる１種以上を含む眼科用剤（但し、ソルビン酸又はその塩０．００１Ｗ／Ｖ％から２Ｗ／Ｖ％、及び非イオン界面活性剤０．００１Ｗ／Ｖ％から２Ｗ／Ｖ％を配合した場合を除く）。 (1) a) pranoprofen 0.005 W / V% to 0.2 W / V% , b) sodium cromoglycate 0.05 W / V% to 3.0 W / V% , and c) edetate salts 0.0001W / V% to 0.15 W / V%, citric acid 0.005 W / V% to 1.0 W / V%, and citrate 0.005 W / V% to 1.0 W / V% Ophthalmic preparations containing one or more of the above (in the case where sorbic acid or a salt thereof is added from 0.001 W / V% to 2 W / V% and a nonionic surfactant from 0.001 W / V% to 2 W / V%) Except) .
（２） ａ）プラノプロフェン０．００５Ｗ／Ｖ％から０．２Ｗ／Ｖ％、ｂ）クロモグリク酸ナトリウム０．０５Ｗ／Ｖ％から３．０Ｗ／Ｖ％、及びｃ）エデト酸塩類０．０００１Ｗ／Ｖ％から０．１５Ｗ／Ｖ％を含む眼科用剤（但し、ソルビン酸又はその塩０．００１Ｗ／Ｖ％から２Ｗ／Ｖ％、及び非イオン界面活性剤０．００１Ｗ／Ｖ％から２Ｗ／Ｖ％を配合した場合を除く）。 (2) a) pranoprofen 0.005 W / V% to 0.2 W / V%, b) sodium cromoglycate 0.05 W / V% to 3.0 W / V%, and c) edetate salts 0.0001 W Ophthalmic preparations containing / V% to 0.15 W / V% (but 0.001 W / V% to 2 W / V% sorbic acid or a salt thereof, and 0.001 W / V% to 2 W / nonionic surfactant) Excluding the case where V% is blended) .
（３） ａ）プラノプロフェン０．００５Ｗ／Ｖ％から０．２Ｗ／Ｖ％、ｂ）クロモグリク酸ナトリウム０．０５Ｗ／Ｖ％から３．０Ｗ／Ｖ％、ｃ）エデト酸塩類０．００１Ｗ／Ｖ％から０．１５Ｗ／Ｖ％を含む眼科用剤（但し、ソルビン酸又はその塩０．００１Ｗ／Ｖ％から２Ｗ／Ｖ％、及び非イオン界面活性剤０．００１Ｗ／Ｖ％から２Ｗ／Ｖ％を配合した場合を除く）。 (3) a) pranoprofen 0.005 W / V% to 0.2 W / V%, b) sodium cromoglycate 0.05 W / V% to 3.0 W / V%, c) edetate salts 0.001 W / Ophthalmic preparations containing V% to 0.15 W / V% (however, sorbic acid or a salt thereof 0.001 W / V% to 2 W / V%, and nonionic surfactant 0.001 W / V% to 2 W / V) %) .
（４） 上記エデト酸塩類は、エチレンジアミン四酢酸二ナトリウム又はエチレンジアミン四酢酸四ナトリウムである（１）〜（３）のいずれかに記載の眼科用剤。(4) The ophthalmic preparation according to any one of (1) to (3), wherein the edetate is disodium ethylenediaminetetraacetate or tetrasodium ethylenediaminetetraacetate.
本発明の眼科用剤によれば、プラノプロフェン及びクロモグリク酸ナトリウムを含む水溶液にエデト酸塩類及びクエン酸又はその塩を添加させることによって、プラノプロフェンの光安定性を向上させることが可能となった。これによって長期保存においても一定の品質を保つ眼科用剤を提供することが可能となった。 According to the ophthalmic agent of the present invention, it is possible to improve the photostability of pranoprofen by adding edetates and citric acid or a salt thereof to an aqueous solution containing pranoprofen and cromoglycate sodium. became. This makes it possible to provide an ophthalmic agent that maintains a certain quality even during long-term storage.
以下、本発明について詳しく説明する。 The present invention will be described in detail below.
本発明に係る眼科用剤は「プラノプロフェン」を含有する。「プラノプロフェン」とは、α−メチル−５Ｈ−〔１〕ベンゾピラノ〔２，３−ｂ〕ピリジン−７−酢酸といい、下記の構造式で示される。プラノプロフェンは、インドメタシンに代表される非ステロイド性鎮痛消炎剤の１つであり、シクロオキシゲナーゼを阻害し、炎症の原因物質プロスタグランジンの生成を抑制することで炎症部位の消炎鎮痛作用を示す物質である。また、プロピオン酸系の非ステロイド性抗炎症剤であり、インドメタシン等に比べて副作用の少ないのが特長である。医療用としては、ニフラン（登録商標）の販売名で市販されている。 The ophthalmic agent according to the present invention contains “planoprofen”. “Pranoprofen” is called α-methyl-5H- [1] benzopyrano [2,3-b] pyridine-7-acetic acid and is represented by the following structural formula. Planoprofen is a non-steroidal analgesic / anti-inflammatory agent typified by indomethacin, which inhibits cyclooxygenase and suppresses the production of prostaglandins that cause inflammation, thereby exhibiting anti-inflammatory analgesia at the site of inflammation. It is. In addition, it is a propionic acid-based non-steroidal anti-inflammatory agent and is characterized by fewer side effects than indomethacin. For medical use, it is marketed under the name Niflan (registered trademark).
本発明に係る点眼液の主薬であるプラノプロフェンの使用濃度は症状に応じて適宜選択することができるが、０．００５〜０．２ｗ／ｖ％であることが好ましく、０．０２５〜０．１ｗ／ｖ％であることが更に好ましい。 The concentration of pranoprofen, which is the main ingredient of the ophthalmic solution according to the present invention, can be appropriately selected according to the symptoms, but is preferably 0.005 to 0.2 w / v%, preferably 0.025 to 0 More preferably, it is 1 w / v%.
また、本発明に係る眼科用剤は「クロモグリク酸ナトリウム」を含有する。「クロモグリク酸ナトリウム」とは、抗アレルギー薬の１つで生薬成分のケリンを原型物質として開発されたものであり、下記の構造式で示される。ＩｇＥ型抗原抗体反応による肥満細胞からのヒスタミン、セロトニン等の化学媒介物質の放出を特異的に抑制することによって作用を発現している。経口的には吸収されないため、ぜん息、アレルギー性鼻炎に際しては粉末状の薬剤を直接吸入するという方法が採られている。 The ophthalmic preparation according to the present invention contains “sodium cromoglycate”. “Sodium cromoglycate” is one of the antiallergic drugs and was developed using the crude drug component, kerin, as a prototype substance, and is represented by the following structural formula. Its action is expressed by specifically inhibiting the release of chemical mediators such as histamine and serotonin from mast cells due to IgE-type antigen-antibody reaction. Since it is not absorbed orally, a method of directly inhaling a powdered drug is employed for asthma and allergic rhinitis.
クロモグリク酸ナトリウムの使用濃度は症状に応じて適宜選択することができるが、０．０５〜３．０ｗ／ｖ％であることが好ましく、０．０１〜２．０ｗ／ｖ％であることが更に好ましい。 The concentration of sodium cromoglycate used can be appropriately selected according to symptoms, but is preferably 0.05 to 3.0 w / v%, more preferably 0.01 to 2.0 w / v%. preferable.
さらにまた、本発明に係る眼科用剤は「エデト酸塩類」を含有する。「エデト酸塩類」とは、エチレンジアミンテトラアセタト錯体の１種であり、本発明においてはエチレンジアミン四酢酸二ナトリウム又はエチレンジアミン四酢酸四ナトリウムをいう。 Furthermore, the ophthalmic preparation according to the present invention contains “edetate salts”. “Edetate” is one kind of ethylenediaminetetraacetate complex, and in the present invention, refers to disodium ethylenediaminetetraacetate or tetrasodium ethylenediaminetetraacetate.
エチレンジアミンテトラアセタト錯体は、エチレンジアミン四酢酸（配位子としての記号ｅｄｔａ）又はそのイオンＨｎｅｄｔａ（４−ｎ）−（ｎ＝０〜４）を配位子とする錯体をいう。１価イオンを除くほとんどすべての金属イオンで安定な錯体を形成するため、ゴムやアスコルビン酸（ビタミンＣ）の酸化防止や、ペプチドの加水分解を防ぐ目的で、ゴム製品、織物、医薬品等の添加剤に用いられている。 The ethylenediaminetetraacetato complex refers to a complex having ethylenediaminetetraacetic acid (symbol edta as a ligand) or its ion H n edta (4-n)- (n = 0 to 4) as a ligand. Addition of rubber products, textiles, pharmaceuticals, etc. for the purpose of preventing oxidation of rubber and ascorbic acid (vitamin C) and preventing hydrolysis of peptides because stable complexes are formed with almost all metal ions except monovalent ions. Used in preparations.
エデト酸塩類の使用濃度は必要に応じて適宜選択することができるが、０．０００１〜０．１５ｗ／ｖ％であることが好ましく、０．００１〜０．１ｗ／ｖ％であることが更に好ましい。また、エチレンジアミン四酢酸二水素二ナトリウム（以下、ＥＤＴＡ−２Ｎａ）を形成する。なお、ＥＤＴＡ−２Ｎａは下記の構造式で示される。 The use concentration of edetates can be appropriately selected as necessary, but is preferably 0.0001 to 0.15 w / v%, and more preferably 0.001 to 0.1 w / v%. preferable. Moreover, disodium ethylenediaminetetraacetate (hereinafter referred to as EDTA-2Na) is formed. EDTA-2Na is represented by the following structural formula.
さらにまた、本発明に係る眼科用剤は「クエン酸又はその塩」を含有する。「クエン酸」とは、ヒドロキシトリカルボン酸の１つをいい、下記の構造式で示される。シトロン、ダイダイ、ミカン等の果実中に遊離して存在し、これから抽出及び製造される。クエン酸は主として清涼飲料水に使用されるが、生理的にはトリカルボン酸サイクル（ＴＣＡサイクル）を構成する物質の１つである。 Furthermore, the ophthalmic agent according to the present invention contains “citric acid or a salt thereof”. “Citric acid” refers to one of hydroxytricarboxylic acids and is represented by the following structural formula. It exists in fruits such as citron, daidai, mandarin orange, and is extracted and produced therefrom. Citric acid is mainly used in soft drinks, but is physiologically one of the substances constituting the tricarboxylic acid cycle (TCA cycle).
クエン酸の塩には、正塩（Ｍ３Ｃ６Ｈ５Ｏ７）の他、水素塩（Ｍ２ＨＣ６Ｈ５Ｏ７，ＭＨ２Ｃ６Ｈ５Ｏ７）が知られている。アルカリ金属塩は水に可溶であり、カリウム塩やナトリウム塩が広く用いられている。本発明における「クエン酸の塩」は特に限定されないが、ナトリウム塩であるクエン酸ナトリウムを用いることが好ましい。 In addition to the normal salt (M 3 C 6 H 5 O 7 ), hydrogen salts (M 2 HC 6 H 5 O 7 , MH 2 C 6 H 5 O 7 ) are known as citric acid salts. Alkali metal salts are soluble in water, and potassium salts and sodium salts are widely used. The “salt of citric acid” in the present invention is not particularly limited, but sodium citrate which is a sodium salt is preferably used.
クエン酸又はその塩の使用濃度は必要に応じて適宜選択することができるが、０．００５〜１．０ｗ／ｖ％であることが好ましく、０．０１〜０．５ｗ／ｖ％であることが更に好ましい。 The use concentration of citric acid or a salt thereof can be appropriately selected as necessary, but is preferably 0.005 to 1.0 w / v%, and 0.01 to 0.5 w / v%. Is more preferable.
本発明に係る眼科用剤にはさらに緩衝剤、等張化剤、溶解補助剤、保存剤、粘稠剤、ｐＨ調整剤のような各種の添加剤を適宜添加してもよい。 Various additives such as a buffer, an isotonic agent, a solubilizing agent, a preservative, a thickener, and a pH adjuster may be added as appropriate to the ophthalmic agent according to the present invention.
緩衝剤としては、例えばリン酸塩緩衝剤（リン酸二水素ナトリウム−リン酸水素二ナトリウム、リン酸二水素カリウム−水酸化カリウム）、ホウ酸緩衝剤（ホウ酸−ホウ砂）、酒石酸塩緩衝剤（酒石酸−酒石酸ナトリウム）、アミノ酸（グルタミン酸ナトリウム、イプシロンアミノカプロン酸）等が挙げられる。 Examples of the buffer include phosphate buffer (sodium dihydrogen phosphate-disodium hydrogen phosphate, potassium dihydrogen phosphate-potassium hydroxide), borate buffer (borate-borax), and tartrate buffer. Agents (tartaric acid-sodium tartrate), amino acids (sodium glutamate, epsilon aminocaproic acid) and the like.
等張化剤としては、ソルビトール、グルコース、マンニトール等の糖類、グリセリン、プロピレングリコール等の多価アルコール類、塩化ナトリウム、ホウ砂等の塩類、ホウ酸等が挙げられる。 Examples of the isotonic agent include saccharides such as sorbitol, glucose and mannitol, polyhydric alcohols such as glycerin and propylene glycol, salts such as sodium chloride and borax, and boric acid.
溶解補助剤としては、ポリオキシエチレンソルビタンモノオレート（ポリソルベート８０）、ポリオキシエチレンモノステアレート、ポリオキシエチレン硬化ヒマシ油等の非イオン界面活性剤、ポリエチレングリコール等が挙げられる。 Examples of the solubilizer include nonionic surfactants such as polyoxyethylene sorbitan monooleate (polysorbate 80), polyoxyethylene monostearate, polyoxyethylene hydrogenated castor oil, and polyethylene glycol.
保存剤としては、塩化ベンザルコニウム、塩化ベンゼトニウム、塩化セチルピリジニウム等の第四級アンモニウム塩、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のパラオキシ安息香酸エステル類、ベンジルアルコール、フェネチルアルコール、ソルビン酸及びそれらの塩、チメロサール、クロロブタノール、デヒドロ酢酸ナトリウム等が挙げられる。 Preservatives include quaternary ammonium salts such as benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride, paraoxybenzoates such as methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, and butyl paraoxybenzoate. Benzyl alcohol, phenethyl alcohol, sorbic acid and salts thereof, thimerosal, chlorobutanol, sodium dehydroacetate and the like.
粘稠剤としては、ポリビニルピロリドン、ヒドロキシエチルセルロース、ヒドロキシプロピルセルロース、メチルセルロース、ヒドロキシプロピルメチルセルロース、カルボキシメチルセルロース及びそれらの塩等が挙げられる。 Examples of the thickener include polyvinyl pyrrolidone, hydroxyethyl cellulose, hydroxypropyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, and salts thereof.
ｐＨ調整剤としては、塩酸、リン酸、酢酸、酒石酸、水酸化ナトリウム、水酸化カリウム、炭酸ナトリウム及び炭酸水素ナトリウム等が挙げられる。 Examples of the pH adjuster include hydrochloric acid, phosphoric acid, acetic acid, tartaric acid, sodium hydroxide, potassium hydroxide, sodium carbonate, and sodium bicarbonate.
本発明に係る眼科用剤は、点眼剤、洗眼剤等として使用される。点眼剤として用いる場合、ｐＨは５．０〜８．５であることが好ましく、５．０〜７．０であることが更に好ましい。また洗眼剤として用いる場合、ｐＨは５．５〜８．０であることが好ましく、５．５〜７．０であることが更に好ましい。 The ophthalmic preparation according to the present invention is used as an eye drop, an eye wash or the like. When used as an eye drop, the pH is preferably 5.0 to 8.5, and more preferably 5.0 to 7.0. When used as an eye wash, the pH is preferably 5.5 to 8.0, more preferably 5.5 to 7.0.
本発明に係る眼科用剤は、従来の方法で点眼剤又は洗眼剤として調製することができる。点眼剤は１日数回、１回１滴から数滴投与することができる。また、洗眼剤は１日数回、目の洗浄をすることができる。 The ophthalmic preparation according to the present invention can be prepared as an eye drop or an eye wash by a conventional method. Eye drops can be administered several times a day, one to several drops at a time. Further, the eye wash can wash the eyes several times a day.
以下に、本発明に係る眼科用剤の製剤処方例を示すが、これらの例は本発明をよりよく理解するためのものであり、本発明の範囲を限定するものではない。 Examples of the pharmaceutical formulation of the ophthalmic agent according to the present invention are shown below, but these examples are for better understanding of the present invention and do not limit the scope of the present invention.
〔実施例１〕
以下に本発明に係る眼科用剤の製造工程を示す。なお、本実施例では点眼剤として用いている。
[Example 1]
The manufacturing process of the ophthalmic preparation according to the present invention is shown below. In this embodiment, it is used as an eye drop.
精製水（８５ｍＬ）にホウ砂、ポリソルベート８０、プラノプロフェンを溶解後、クロモグリク酸ナトリウム及びＥＤＴＡ−２Ｎａ他各成分を添加し、溶解させ、希塩酸でｐＨを５．８に調節した後、全量を１００ｍＬとした。このときの水溶液の外観は無色透明であった。 After dissolving borax, polysorbate 80 and pranoprofen in purified water (85 mL), add cromoglycate sodium, EDTA-2Na and other components, dissolve, adjust the pH to 5.8 with dilute hydrochloric acid, 100 mL. The appearance of the aqueous solution at this time was colorless and transparent.
〔実施例２〕
実施例１の眼科用剤に添加したＥＤＴＡ−２Ｎａの代わりにクエン酸及びクエン酸ナトリウムを添加させた眼科用剤を本実施例における眼科用剤とした。
[Example 2]
An ophthalmic agent in which citric acid and sodium citrate were added instead of EDTA-2Na added to the ophthalmic agent of Example 1 was used as the ophthalmic agent in this example.
〔比較例１〕
本発明の比較例として、プラノプロフェンのみを添加させた眼科用剤を作成した。
[Comparative Example 1]
As a comparative example of the present invention, an ophthalmic agent to which only pranoprofen was added was prepared.
〔比較例２〕
また比較例２として、比較例１のプラノプロフェンの代わりにクロモグリク酸ナトリウムのみを添加させた眼科用剤を作成した。
[Comparative Example 2]
Further, as Comparative Example 2, an ophthalmic preparation was prepared in which only sodium cromoglycate was added instead of pranoprofen of Comparative Example 1.
〔比較例３〕
また比較例３として、比較例１にクロモグリク酸ナトリウムを添加させた眼科用剤を作成した。
[Comparative Example 3]
Further, as Comparative Example 3, an ophthalmic preparation prepared by adding sodium cromoglycate to Comparative Example 1 was prepared.
〔比較例４〕
また比較例４として、比較例１にＥＤＴＡ−２Ｎａ、ホウ酸、塩化ベンザルコニウムを添加させた眼科用剤を作成した。
[Comparative Example 4]
Further, as Comparative Example 4, an ophthalmic preparation was prepared by adding EDTA-2Na, boric acid, and benzalkonium chloride to Comparative Example 1.
〔実施例３〕
上記の眼科用剤を無色のガラス瓶に入れ、３０００ルクスのもと６日間放置し、その外観観察を行なった。このときの結果を表１に示す。
Example 3
The above ophthalmic preparation was placed in a colorless glass bottle and allowed to stand for 6 days under 3000 lux, and the appearance was observed. The results are shown in Table 1.
Claims (2)
ｂ）クロモグリク酸ナトリウム０．５Ｗ／Ｖ％から３．０Ｗ／Ｖ％、
ｃ）エデト酸塩類０．０１Ｗ／Ｖ％から０．１５Ｗ／Ｖ％、クエン酸０．０１Ｗ／Ｖ％から１．０Ｗ／Ｖ％、及びクエン酸塩０．１Ｗ／Ｖ％から１．０Ｗ／Ｖ％、からなる群から選ばれる１種以上、並びに、
ｄ）ホウ砂及びポリオキシエチレンソルビタンモノオレートを含み、ｐＨが５．０から７．０である眼科用剤（但し、ソルビン酸又はその塩０．００１Ｗ／Ｖ％から２Ｗ／Ｖ％、及び非イオン界面活性剤０．００１Ｗ／Ｖ％から２Ｗ／Ｖ％を配合した場合を除く）。 a) pranoprofen 0.0 5 W / V%,
b) Sodium cromoglycate 0. 5 W / V% to 3.0 W / V% ,
c) edetate salts 0.0 1 W / V% from 0.15W / V%, 1.0W / V % from 0.0 1 W / V% citric acid, and citrate 0. 1 or more selected from the group consisting of 1 W / V% to 1.0 W / V% , and
d) an ophthalmic agent comprising borax and polyoxyethylene sorbitan monooleate and having a pH of 5.0 to 7.0 (provided that sorbic acid or a salt thereof is 0.001 W / V% to 2 W / V%, and non Except when ionic surfactant is added in an amount of 0.001 W / V% to 2 W / V%).
The ophthalmic preparation according to claim 1 , wherein the edetate is disodium ethylenediaminetetraacetate or tetrasodium ethylenediaminetetraacetate.
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