JP2671353C - - Google Patents
Info
- Publication number
- JP2671353C JP2671353C JP2671353C JP 2671353 C JP2671353 C JP 2671353C JP 2671353 C JP2671353 C JP 2671353C
- Authority
- JP
- Japan
- Prior art keywords
- amount
- present
- chondroitin sulfate
- weight
- chloride
- 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
- 239000003889 eye drop Substances 0.000 claims description 11
- 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 claims description 9
- 239000002736 nonionic surfactant Substances 0.000 claims description 9
- LPLVUJXQOOQHMX-MYOOOWEVSA-N Glycyrrhizic acid Natural products O=C(O)[C@H]1[C@@H](O)[C@H](O)[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)[C@H](C(=O)O)O2)[C@@H](O[C@@H]2C(C)(C)[C@H]3[C@@](C)([C@H]4C(=O)C=C5[C@](C)([C@]4(C)CC3)CC[C@]3(C)[C@H]5C[C@](C(=O)O)(C)CC3)CC2)O1 LPLVUJXQOOQHMX-MYOOOWEVSA-N 0.000 claims description 8
- 239000001685 glycyrrhizic acid Substances 0.000 claims description 8
- 229960004949 glycyrrhizic acid Drugs 0.000 claims description 8
- 235000019410 glycyrrhizin Nutrition 0.000 claims description 8
- 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 claims description 8
- 239000011780 sodium chloride Substances 0.000 claims description 8
- 229940012356 Eye Drops Drugs 0.000 claims description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-O ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 7
- 239000003093 cationic surfactant Substances 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 6
- 229940054534 Ophthalmic Solution Drugs 0.000 claims description 3
- 239000002997 ophthalmic solution Substances 0.000 claims description 3
- -1 fatty acid ester Chemical class 0.000 description 5
- 229940068968 Polysorbate 80 Drugs 0.000 description 4
- 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 4
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 4
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 4
- 229920000053 polysorbate 80 Polymers 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000004328 sodium tetraborate Substances 0.000 description 4
- 235000010339 sodium tetraborate Nutrition 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 3
- DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical compound C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 description 3
- KGBXLFKZBHKPEV-UHFFFAOYSA-N Boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 3
- 229940116229 Borneol Drugs 0.000 description 3
- 229940101029 Dipotassium Glycyrrhizinate Drugs 0.000 description 3
- 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 3
- 229960004873 LEVOMENTHOL Drugs 0.000 description 3
- 229940041616 Menthol Drugs 0.000 description 3
- 239000004327 boric acid Substances 0.000 description 3
- 229930006709 borneol Natural products 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 229960000686 Benzalkonium Chloride Drugs 0.000 description 2
- 229960001950 Benzethonium Chloride Drugs 0.000 description 2
- 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 2
- DSSYKIVIOFKYAU-UHFFFAOYSA-N Camphor Chemical compound C1CC2(C)C(=O)CC1C2(C)C DSSYKIVIOFKYAU-UHFFFAOYSA-N 0.000 description 2
- 229960000846 Camphor Drugs 0.000 description 2
- 229960001927 Cetylpyridinium Chloride Drugs 0.000 description 2
- YMKDRGPMQRFJGP-UHFFFAOYSA-M Cetylpyridinium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+]1=CC=CC=C1 YMKDRGPMQRFJGP-UHFFFAOYSA-M 0.000 description 2
- 229940046978 Chlorpheniramine Maleate Drugs 0.000 description 2
- 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 2
- 229920001287 Chondroitin sulfate Polymers 0.000 description 2
- 241000723346 Cinnamomum camphora Species 0.000 description 2
- ZAKOWWREFLAJOT-CEFNRUSXSA-N D-α-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 description 2
- 229960002253 Neostigmine Methylsulfate Drugs 0.000 description 2
- 229920001214 Polysorbate 60 Polymers 0.000 description 2
- 229960004172 Pyridoxine Hydrochloride Drugs 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 229960001452 alpha-Tocopherol Acetate Drugs 0.000 description 2
- 229930007890 camphor Natural products 0.000 description 2
- 229960003291 chlorphenamine Drugs 0.000 description 2
- 229940059329 chondroitin sulfate Drugs 0.000 description 2
- 239000002826 coolant Substances 0.000 description 2
- 229960002104 cyanocobalamin Drugs 0.000 description 2
- 235000000639 cyanocobalamin Nutrition 0.000 description 2
- 239000011666 cyanocobalamin Substances 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 239000000194 fatty acid Substances 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
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 230000002335 preservative Effects 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- ZUFQODAHGAHPFQ-UHFFFAOYSA-N pyridoxine hydrochloride Chemical compound Cl.CC1=NC=C(CO)C(CO)=C1O ZUFQODAHGAHPFQ-UHFFFAOYSA-N 0.000 description 2
- 235000019171 pyridoxine hydrochloride Nutrition 0.000 description 2
- 239000011764 pyridoxine hydrochloride Substances 0.000 description 2
- 229960000342 retinol acetate Drugs 0.000 description 2
- 235000019173 retinyl acetate Nutrition 0.000 description 2
- 239000011770 retinyl acetate Substances 0.000 description 2
- QGNJRVVDBSJHIZ-QHLGVNSISA-N retinyl acetate Chemical compound CC(=O)OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C QGNJRVVDBSJHIZ-QHLGVNSISA-N 0.000 description 2
- 230000003381 solubilizing Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- ILRKKHJEINIICQ-UFTZEXNXSA-N (2S,3S,4S,5R,6R)-6-[(3R,4S,5S,6S)-2-[[(3S,4aR,6aR,6bS,8aS,11S,12aR,14aR,14bS)-11-carboxy-4,4,6a,6b,8a,11,14b-heptamethyl-14-oxo-2,3,4a,5,6,7,8,9,10,12,12a,14a-dodecahydro-1H-picen-3-yl]oxy]-6-carboxy-4,5-dihydroxyoxan-3-yl]oxy-3,4,5-trihydroxyoxane-2-carb Chemical compound N.O([C@@H]1[C@@H](O)[C@H](O)[C@H](OC1O[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 ILRKKHJEINIICQ-UFTZEXNXSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N 1,2-ethanediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- VUKAUDKDFVSVFT-UHFFFAOYSA-N 2-[6-[4,5-bis(2-hydroxypropoxy)-2-(2-hydroxypropoxymethyl)-6-methoxyoxan-3-yl]oxy-4,5-dimethoxy-2-(methoxymethyl)oxan-3-yl]oxy-6-(hydroxymethyl)-5-methoxyoxane-3,4-diol Chemical compound COC1C(OC)C(OC2C(C(O)C(OC)C(CO)O2)O)C(COC)OC1OC1C(COCC(C)O)OC(OC)C(OCC(C)O)C1OCC(C)O VUKAUDKDFVSVFT-UHFFFAOYSA-N 0.000 description 1
- CWSZBVAUYPTXTG-UHFFFAOYSA-N 5-[6-[[3,4-dihydroxy-6-(hydroxymethyl)-5-methoxyoxan-2-yl]oxymethyl]-3,4-dihydroxy-5-[4-hydroxy-3-(2-hydroxyethoxy)-6-(hydroxymethyl)-5-methoxyoxan-2-yl]oxyoxan-2-yl]oxy-6-(hydroxymethyl)-2-methyloxane-3,4-diol Chemical compound O1C(CO)C(OC)C(O)C(O)C1OCC1C(OC2C(C(O)C(OC)C(CO)O2)OCCO)C(O)C(O)C(OC2C(OC(C)C(O)C2O)CO)O1 CWSZBVAUYPTXTG-UHFFFAOYSA-N 0.000 description 1
- SLXKOJJOQWFEFD-UHFFFAOYSA-N Aminocaproic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 1
- 229940009098 Aspartate Drugs 0.000 description 1
- 210000004087 Cornea Anatomy 0.000 description 1
- CKLJMWTZIZZHCS-UHFFFAOYSA-N DL-aspartic acid Chemical compound OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 1
- 229960000525 Diphenhydramine Hydrochloride Drugs 0.000 description 1
- 229940093632 Flavin-Adenine Dinucleotide Drugs 0.000 description 1
- 206010018910 Haemolysis Diseases 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 102000016943 Muramidase Human genes 0.000 description 1
- 108010014251 Muramidase Proteins 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- XOAAWQZATWQOTB-UHFFFAOYSA-N Taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 1
- 229940042585 Tocopherol Acetate Drugs 0.000 description 1
- 229940029983 VITAMINS Drugs 0.000 description 1
- 229930003270 Vitamin B Natural products 0.000 description 1
- RMRCNWBMXRMIRW-WYVZQNDMSA-L Vitamin B12 Chemical compound N([C@@H]([C@@]1(C)[C@@](C)(CC(N)=O)[C@H](CCC(N)=O)\C(N1[Co+]C#N)=C(/C)\C1=N\C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C\C1=N\C([C@H](C1(C)C)CCC(N)=O)=C/1C)[C@@H]2CC(N)=O)=C\1[C@]2(C)CCC(=O)NCC(C)OP([O-])(=O)O[C@H]1[C@@H](O)[C@@H](N2C3=CC(C)=C(C)C=C3N=C2)O[C@@H]1CO RMRCNWBMXRMIRW-WYVZQNDMSA-L 0.000 description 1
- 229940021016 Vitamin IV solution additives Drugs 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000003732 agents acting on the eye Substances 0.000 description 1
- 229960002684 aminocaproic acid Drugs 0.000 description 1
- 230000000844 anti-bacterial Effects 0.000 description 1
- 230000003110 anti-inflammatory Effects 0.000 description 1
- SIYLLGKDQZGJHK-UHFFFAOYSA-N benzyl-dimethyl-[2-[2-[4-(2,4,4-trimethylpentan-2-yl)phenoxy]ethoxy]ethyl]azanium Chemical compound C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 SIYLLGKDQZGJHK-UHFFFAOYSA-N 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M buffer Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- PCHPORCSPXIHLZ-UHFFFAOYSA-N diphenhydramine hydrochloride Chemical compound [Cl-].C=1C=CC=CC=1C(OCC[NH+](C)C)C1=CC=CC=C1 PCHPORCSPXIHLZ-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drugs Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 235000019162 flavin adenine dinucleotide Nutrition 0.000 description 1
- 239000011714 flavin adenine dinucleotide Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229940074774 glycyrrhizinate Drugs 0.000 description 1
- LPLVUJXQOOQHMX-QWBHMCJMSA-K glycyrrhizinate(3-) 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-K 0.000 description 1
- 230000002949 hemolytic Effects 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 239000004325 lysozyme Substances 0.000 description 1
- 235000010335 lysozyme Nutrition 0.000 description 1
- 229960000274 lysozyme Drugs 0.000 description 1
- 239000001525 mentha piperita l. herb oil Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000003020 moisturizing Effects 0.000 description 1
- 231100000017 mucous membrane irritation Toxicity 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 235000019477 peppermint oil Nutrition 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 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
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000001681 protective Effects 0.000 description 1
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 description 1
- 231100000486 side effect Toxicity 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000019156 vitamin B Nutrition 0.000 description 1
- 239000011720 vitamin B Substances 0.000 description 1
- 229930003231 vitamins Natural products 0.000 description 1
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明はコンドロイチン硫酸ナトリウムを含有する点眼剤に関し、更に詳しく
は、コンドロイチン硫酸ナトリウムに第４級アンモニウム性陽イオン界面活性剤
を配合する系に生じる白濁を解消した点眼剤に関する。
〔従来の技術〕
従来、点眼剤においてコンドロイチン硫酸ナト
リウムは角膜保護作用、組織修復作用、粘稠（保湿）作用等を有する薬効成分と
して繁用されており、塩化ベンザルコニウム等の第４級アンモニウム性陽イオン
界面活性剤は効果的な保存剤として多用されるものである。しかし、この２成分
が共存すると、白濁現象が発生する。
一般に、この様な白濁が生じた場合、非イオン界面活性剤（例えばポリオキシ
エチレンソルビタン脂肪酸エステル）等の溶解補助剤を添加して白濁を解消して
いた。
〔発明が解決しようとする課題〕
しかしながら近年は点眼感の改善、向上の理由からメントール、ボルネオール
あるいはカンフル等の清涼化剤を配合する傾向にある。上記の２成分の系にこれ
らの清涼化剤を配合する場合には白濁現象が一層顕著になるので、溶解補助剤を
更に多量に配合しなければならない。
ところが、溶解補助剤として使用される非イオン界面活性剤は一般的にその可
溶化能力に優れた物質であるが、連用すると溶血作用、粘膜刺激作
用等副作用が懸念されている。更には保存剤である第４級アンモニウム性陽イオ
ン界面活性剤の抗菌力を低下させたり、不活性化させるという弊害がある。そこ
で、非イオン界面活性剤の配合量を可能な限り少量使用に押さえた点眼剤が望ま
れていた。
〔課題を解決するための手段〕
本発明者らは、コンドロイチン硫酸ナトリウムと第４級アンモニウム性陽イオ
ン界面活性剤により生成する白濁現象と、これを澄明化する非イオン界面活性剤
との反応系に着目し、鋭意検討を加えた結果、グリチルリチン酸又はその塩類を
添加することによってその可溶化作用は相乗的に増大することを発見し、本発明
を完成した。
すなわち、本発明は、コンドロイチン硫酸ナトリウム及び第４級アンモニウム
性陽イオン界面活性剤を含有する系に、非イオン界面活性剤を点眼剤全量に対し
て０．０２〜０．１０重量％、及びグリチルリチン酸又はその塩０．０１〜０．
３０重量％を添加することを特徴とする点眼剤である。
以下、本発明を詳細に説明する。
本発明で用いるグリチルリチン酸又はその塩類の添加量は、点眼剤全量に対し
て０．０１〜０．３０重量％、好ましくは０．０２〜０．１５重量％である。
また、溶解補助剤として用いる非イオン界面活性剤の添加量は０．０２〜０．
１０重量％で、従来の１／１０〜１／２量である。
この非イオン界面活性剤の種類としては、ポリソルベート８０等のポリオキシ
エチレンソルビタン脂肪酸エステル類の他、ポリオキシエチレン硬化ヒマシ油類
等が挙げられる。
第４級アンモニウム性陽イオン界面活性剤としては、塩化ベンザルコニウムの
他、塩化ベンゼトニウム、塩化セチルピリジニウム等が挙げられる。
また、グリチルリチン酸又はその塩としてはグリチルリチン酸、グリチルリチ
ン酸二カリウム、グリチルリチン酸二ナトリウム、グリチルリチン酸モノアンモ
ニウム等がある。
本発明の点眼剤では、内容成分の安定性からそのｐＨは５．８以下が望ましい
。
本発明においては、前記した必須の成分の他に点眼剤の調製に通常使用する各
種成分をその通常使用量において配合することができる。
例えば有効成分としてサルファ剤、塩酸ジフェンヒドラミン、アスパラギン酸
塩、アミノエチルスルホン酸、塩化リゾチーム、イプシロンアミノカプロン酸、
マレイン酸クロルフェニラミン、メチル硫酸ネオスチグミン、各種ビタミン類（
例えば活性型ビタミンＢ2［フラビンアデニンジヌクレオタイドナトリウム］、
ビタミンＢ6［塩酸ピリドキシン］、ビタミンＢ12［シアノコバラミン］、ビタ
ミンＡ酢酸エステル［酢酸レチノール］、ビタミンＥ酢酸エステル［酢酸トコフ
ェロール］等）を配合することができる。
また、必要に応じて清涼化剤（例えばメントール、ボルネオール、カンフル、
ハッカ油等）、等張化剤（例えば塩化ナトリウム、塩化カリウム等）、高分子添
加剤（例えば多価アルコール、ポリ
ビニルアルコール、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
ロキシプロピルメチルセルロース等）、安定化剤（例えばエチレンジアミン四酢
酸塩等）、緩衝剤（例えばホウ酸、ホウ砂等）等を配合することができる。
本発明で使用されるグリチルリチン酸又はその塩は、元来、消炎作用を有し、
厚生省眼科用薬承認基準にも記載されている成分で、連用しても副作用のほとん
どない、安全性の高い成分として知られているものである。
〔発明の効果〕
本発明により非イオン界面活性剤の添加量を従来の１／１０〜１／２量に減量
することが可能となり、安全性が向上し、かつ点眼感の向上した澄明な点眼剤を
提供することが可能となった。
〔実施例〕
以下、本発明の実施例を示すが、これによって本発明を限定するものではない
。
（実施例１）
下記処方に従い点眼剤を調製した。
〔成分名〕 ［配合量mg/100ml］
マレイン酸クロルフェニラミン ２０
コンドロイチン硫酸ナトリウム １００
塩酸ピリドキシン １００
塩化ベンザルコニウム １５
ポリソルベート８０ ５０
ホウ酸 ８００
ホウ砂 ５０
塩化ナトリウム ５０
グリチルリチン酸 ２０
滅菌精製水 全１００mlとする
（実施例２）
〔成分名〕 ［配合量mg/100ml］
メチル硫酸ネオスチグミン ２
コンドロイチン硫酸ナトリウム １００
塩化ベンゼトニウム ２０
ポリソルベート８０ １００
ホウ酸 １０００
ホウ砂 ４０
メントール ３０
ボルネオール ５
グリチルリチン酸二カリウム １５０
滅菌精製水 全１００mlとする
（実施例３）
〔成分名〕 ［配合量mg/100ml］
シアノコバラミン １０
コンドロイチン硫酸ナトリウム １００
塩化セチルピリジニウム ５
ポリソルベート８０ ２０
ホウ酸 １０００
ホウ砂 ９０
グリチルリチン酸二カリウム ５０
滅菌精製水 全１００mlとするDescription: TECHNICAL FIELD The present invention relates to an ophthalmic solution containing chondroitin sulfate, and more particularly, to a system in which sodium chondroitin sulfate is mixed with a quaternary ammonium cationic surfactant. The present invention relates to an ophthalmic solution which eliminates clouding that occurs. [Related Art] Conventionally, sodium chondroitin sulfate has been widely used as an active ingredient having a cornea protective action, a tissue repair action, a viscous (moisturizing) action and the like in eye drops, and a quaternary ammonium such as benzalkonium chloride. Soluble cationic surfactants are frequently used as effective preservatives. However, when these two components coexist, a cloudiness phenomenon occurs. Generally, when such cloudiness occurs, a solubilizing agent such as a nonionic surfactant (eg, polyoxyethylene sorbitan fatty acid ester) is added to eliminate cloudiness. [Problems to be Solved by the Invention] However, in recent years, there has been a tendency to incorporate a refreshing agent such as menthol, borneol or camphor for reasons of improvement and improvement of eye drop. When these cooling agents are added to the above two-component system, the clouding phenomenon becomes more remarkable, so that a larger amount of a solubilizing agent must be added. However, nonionic surfactants used as solubilizers are generally excellent in solubilizing ability. However, if they are used continuously, there are concerns about side effects such as hemolysis and mucosal irritation. Further, there is a problem that the antibacterial activity of the quaternary ammonium cationic surfactant as a preservative is reduced or inactivated. Therefore, an eye drop in which the compounding amount of the nonionic surfactant is kept to a minimum amount is desired. [Means for Solving the Problems] The present inventors have developed a reaction system between a chondroitin sulfate and a quaternary ammonium cationic surfactant and a non-ionic surfactant which clarifies the phenomenon. As a result of intensive studies, they have found that the addition of glycyrrhizic acid or a salt thereof synergistically increases the solubilizing action, and completed the present invention. That is, the present invention relates to a system containing sodium chondroitin sulfate and a quaternary ammonium cationic surfactant, wherein a nonionic surfactant is added to the total amount of eye drops.
Glycyrrhizic acid or a salt thereof from 0.01 to 0.10% by weight .
An eye drop characterized by adding 30% by weight . Hereinafter, the present invention will be described in detail. The amount of glycyrrhizic acid or a salt thereof used in the present invention is 0.01 to 0.30% by weight, preferably 0.02 to 0.15% by weight, based on the total amount of the eye drops. The amount of the nonionic surfactant used as a solubilizing agent is 0.02 to 0.5.
At 10% by weight, it is 1/10 to 1/2 of the conventional amount. Examples of the type of the nonionic surfactant include polyoxyethylene sorbitan fatty acid esters such as polysorbate 80, and polyoxyethylene hydrogenated castor oil. Examples of the quaternary ammonium cationic surfactant include benzathonium chloride, benzethonium chloride, cetylpyridinium chloride and the like. Examples of glycyrrhizic acid or a salt thereof include glycyrrhizic acid, dipotassium glycyrrhizinate, disodium glycyrrhizinate, and monoammonium glycyrrhizinate. In the eye drops of the present invention, the pH is desirably 5.8 or less from the stability of the content components. In the present invention, in addition to the essential components described above, various components usually used in the preparation of eye drops can be blended in their usual amounts. For example, as active ingredients, sulfa drugs, diphenhydramine hydrochloride, aspartate, aminoethylsulfonic acid, lysozyme chloride, epsilon aminocaproic acid,
Chlorpheniramine maleate, neostigmine methyl sulfate, various vitamins (
For example, active vitamin B 2 [flavin adenine dinucleotide sodium],
Vitamin B 6 [pyridoxine hydrochloride], vitamin B 12 [cyanocobalamin], vitamin A acetate [retinol acetate], vitamin E acetate [tocopherol acetate], etc.) can be added. If necessary, a cooling agent (eg, menthol, borneol, camphor,
Peppermint oil, etc.), tonicity agents (eg, sodium chloride, potassium chloride, etc.), polymer additives (eg, polyhydric alcohol, polyvinyl alcohol, polyvinylpyrrolidone, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, etc.), stabilizers (eg, ethylene diamine) Tetraacetate, etc.), buffers (for example, boric acid, borax, etc.) and the like. Glycyrrhizic acid or a salt thereof used in the present invention originally has an anti-inflammatory effect,
It is a component listed in the Ministry of Health and Welfare Ophthalmic Drug Approval Standard, and is known as a highly safe component that has almost no side effects even when used continuously. [Effects of the Invention] The present invention makes it possible to reduce the amount of the nonionic surfactant to 1/10 to 1/2 of the conventional amount, thereby improving the safety and clearing the eye drops. Agent can be provided. EXAMPLES Hereinafter, examples of the present invention will be described, but the present invention is not limited thereto. (Example 1) An eye drop was prepared according to the following formulation. [Component name] [Blending amount mg / 100ml] Chlorpheniramine maleate 20 Sodium chondroitin sulfate 100 Pyridoxine hydrochloride 100 Benzalkonium chloride 15 Polysorbate 80 50 Boric acid 800 Borax 50 Sodium chloride 50 Glycyrrhizic acid 20 (Example 2) [Component name] [Blending amount mg / 100 ml] Neostigmine methyl sulfate 2 Sodium chondroitin sulfate 100 Benzethonium chloride 20 Polysorbate 80 100 Boric acid 1000 Borax 40 Menthol 30 Borneol 5 Dipotassium glycyrrhizinate 150 Sterilized purified water All 100 ml (Example 3) [Component name] [Blending amount mg / 100 ml] Cyanocobalamin 10 Sodium chondroitin sulfate 100 Cetylpyridinium chloride 5 Polysorbate 80 And 0 borate 1000 Borax 90 dipotassium glycyrrhizinate 50 sterile purified water total 100ml
Claims (1)
剤を含有する系に、非イオン界面活性剤を点眼剤全量に対して０．０２〜０．１
０重量％、及びグリチルリチン酸又はその塩０．０１〜０．３０重量％を添加す
ることを特徴とする点眼剤。Claims: (1) A system containing sodium chondroitin sulfate and a quaternary ammonium cationic surfactant is mixed with a nonionic surfactant in an amount of 0.02 to 0.1 with respect to the total amount of eye drops.
An ophthalmic solution comprising 0% by weight and 0.01 to 0.30% by weight of glycyrrhizic acid or a salt thereof.
Family
ID=
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2379605C (en) | Topical suspension formulations containing ciprofloxacin and dexamethasone | |
| TWI498122B (en) | Aqueous pharmaceutical compositions containing borate-polyol complexes | |
| KR101690817B1 (en) | Ophthalmic composition | |
| JP3689123B2 (en) | Vitamin A solubilized aqueous eye drops | |
| JP2003183157A (en) | Ophthalmologic composition | |
| EP1759702A1 (en) | Method of preparing a latanoprost ophthalmic solution and solution thus produced | |
| KR20160123400A (en) | Self-preserved emulsions | |
| JP3142842B1 (en) | Ophthalmic composition and method for suppressing adsorption to soft contact lens | |
| JP2005330276A (en) | Antiseptic and water-based composition containing the same | |
| EP0976407A1 (en) | Antiseptic composition | |
| JP2003252800A (en) | External composition for mucosa | |
| JP5729109B2 (en) | Ophthalmic composition for soft contact lenses | |
| JP5176132B2 (en) | Ophthalmic agent | |
| JP2003206241A (en) | Ophthalmic agent | |
| JP2002316926A (en) | Ophthalmic composition for contact lens and method for mitigating ocular irritation | |
| JP2003002837A (en) | Composition for aqueous skin care preparation and method for preventing clouding of liquid composition | |
| JP2671353B2 (en) | Eye drops | |
| JP5584336B2 (en) | Preservative and aqueous composition containing the same | |
| JP4844706B2 (en) | Ophthalmic composition | |
| JP5834427B2 (en) | Adsorption suppression method for soft contact lenses | |
| JP2011246383A (en) | Ophthalmologic formulation for alleviation of tired eyes of contact lens wearer | |
| JP4801300B2 (en) | Liquid composition for external use | |
| JP5013735B2 (en) | Ocular mucosa application | |
| JP4442118B2 (en) | Stable eye drops | |
| JP2003073303A (en) | Method for maintaining refreshing activity of eye drops |