JP2010106015A - Ophthalmic solution - Google Patents
Ophthalmic solution Download PDFInfo
- Publication number
- JP2010106015A JP2010106015A JP2009223686A JP2009223686A JP2010106015A JP 2010106015 A JP2010106015 A JP 2010106015A JP 2009223686 A JP2009223686 A JP 2009223686A JP 2009223686 A JP2009223686 A JP 2009223686A JP 2010106015 A JP2010106015 A JP 2010106015A
- Authority
- JP
- Japan
- Prior art keywords
- eye drop
- benzalkonium chloride
- contact lens
- emulsion
- eye
- 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
- 239000002997 ophthalmic solution Substances 0.000 title claims abstract description 7
- 229940054534 ophthalmic solution Drugs 0.000 title claims abstract description 7
- 229960000686 benzalkonium chloride Drugs 0.000 claims abstract description 33
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 claims abstract description 33
- 239000003921 oil Substances 0.000 claims abstract description 16
- -1 liquid paraffin Substances 0.000 claims abstract description 14
- 229920003169 water-soluble polymer Polymers 0.000 claims abstract description 12
- 239000004359 castor oil Substances 0.000 claims abstract description 11
- 235000019438 castor oil Nutrition 0.000 claims abstract description 11
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims abstract description 11
- 229940057995 liquid paraffin Drugs 0.000 claims abstract description 11
- 239000004166 Lanolin Substances 0.000 claims abstract description 10
- 229960001777 castor oil Drugs 0.000 claims abstract description 10
- 229940039717 lanolin Drugs 0.000 claims abstract description 10
- 235000019388 lanolin Nutrition 0.000 claims abstract description 10
- 235000019271 petrolatum Nutrition 0.000 claims abstract description 10
- ZSZRUEAFVQITHH-UHFFFAOYSA-N 2-(2-methylprop-2-enoyloxy)ethyl 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CC(=C)C(=O)OCCOP([O-])(=O)OCC[N+](C)(C)C ZSZRUEAFVQITHH-UHFFFAOYSA-N 0.000 claims abstract description 9
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 claims abstract description 9
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims abstract description 9
- 239000004264 Petrolatum Substances 0.000 claims abstract description 8
- 229920001577 copolymer Polymers 0.000 claims abstract description 8
- 229940066842 petrolatum Drugs 0.000 claims abstract description 8
- 239000003889 eye drop Substances 0.000 claims description 56
- 239000000839 emulsion Substances 0.000 claims description 31
- 229940012356 eye drops Drugs 0.000 claims description 21
- 238000001179 sorption measurement Methods 0.000 abstract description 16
- 239000000243 solution Substances 0.000 abstract description 14
- 239000000126 substance Substances 0.000 abstract 1
- 239000002504 physiological saline solution Substances 0.000 description 10
- 229920000642 polymer Polymers 0.000 description 10
- 239000002245 particle Substances 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 239000003755 preservative agent Substances 0.000 description 9
- 238000000034 method Methods 0.000 description 8
- 230000000052 comparative effect Effects 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 238000001914 filtration Methods 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 230000002335 preservative effect Effects 0.000 description 4
- 239000012488 sample solution Substances 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 229960001716 benzalkonium Drugs 0.000 description 3
- CYDRXTMLKJDRQH-UHFFFAOYSA-N benzododecinium Chemical compound CCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 CYDRXTMLKJDRQH-UHFFFAOYSA-N 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
- 230000007423 decrease Effects 0.000 description 3
- 239000003995 emulsifying agent Substances 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 206010015946 Eye irritation Diseases 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 208000025174 PANDAS Diseases 0.000 description 2
- 208000021155 Paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection Diseases 0.000 description 2
- 240000004718 Panda Species 0.000 description 2
- 235000016496 Panda oleosa Nutrition 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000002421 anti-septic effect Effects 0.000 description 2
- 239000000607 artificial tear Substances 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- RMRCNWBMXRMIRW-BYFNXCQMSA-M cyanocobalamin Chemical compound N#C[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O RMRCNWBMXRMIRW-BYFNXCQMSA-M 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 231100000013 eye irritation Toxicity 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 238000007654 immersion Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000000787 lecithin Substances 0.000 description 2
- 235000010445 lecithin Nutrition 0.000 description 2
- 229940067606 lecithin Drugs 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 239000002736 nonionic surfactant Substances 0.000 description 2
- 238000004513 sizing Methods 0.000 description 2
- 150000005846 sugar alcohols Polymers 0.000 description 2
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 1
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 1
- SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- DBAKFASWICGISY-BTJKTKAUSA-N Chlorpheniramine maleate Chemical compound OC(=O)\C=C/C(O)=O.C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 DBAKFASWICGISY-BTJKTKAUSA-N 0.000 description 1
- 241000723346 Cinnamomum camphora Species 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-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
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 206010020565 Hyperaemia Diseases 0.000 description 1
- ZCVMWBYGMWKGHF-UHFFFAOYSA-N Ketotifene Chemical compound C1CN(C)CCC1=C1C2=CC=CC=C2CC(=O)C2=C1C=CS2 ZCVMWBYGMWKGHF-UHFFFAOYSA-N 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
- 238000009825 accumulation Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 229960004050 aminobenzoic acid Drugs 0.000 description 1
- 229960002684 aminocaproic acid Drugs 0.000 description 1
- ALYNCZNDIQEVRV-UHFFFAOYSA-N aniline-p-carboxylic acid Natural products NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 1
- 230000003266 anti-allergic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 239000012298 atmosphere Substances 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
- 229960001950 benzethonium chloride Drugs 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 229960002645 boric acid Drugs 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 210000005252 bulbus oculi Anatomy 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 229960000846 camphor Drugs 0.000 description 1
- 229930008380 camphor Natural products 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229960003333 chlorhexidine gluconate Drugs 0.000 description 1
- YZIYKJHYYHPJIB-UUPCJSQJSA-N chlorhexidine gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O.C1=CC(Cl)=CC=C1NC(=N)NC(=N)NCCCCCCNC(=N)NC(=N)NC1=CC=C(Cl)C=C1 YZIYKJHYYHPJIB-UUPCJSQJSA-N 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 229940046978 chlorpheniramine maleate Drugs 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- 239000002826 coolant Substances 0.000 description 1
- 229960002104 cyanocobalamin Drugs 0.000 description 1
- 235000000639 cyanocobalamin Nutrition 0.000 description 1
- 239000011666 cyanocobalamin Substances 0.000 description 1
- 238000007872 degassing Methods 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229960001484 edetic acid Drugs 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 231100000040 eye damage Toxicity 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000001678 irradiating effect Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 229960004958 ketotifen Drugs 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 229940041616 menthol Drugs 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
- 239000007764 o/w emulsion Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000136 polysorbate Polymers 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
- ZUFQODAHGAHPFQ-UHFFFAOYSA-N pyridoxine hydrochloride Chemical compound Cl.CC1=NC=C(CO)C(CO)=C1O ZUFQODAHGAHPFQ-UHFFFAOYSA-N 0.000 description 1
- 229960004172 pyridoxine hydrochloride Drugs 0.000 description 1
- 235000019171 pyridoxine hydrochloride Nutrition 0.000 description 1
- 239000011764 pyridoxine hydrochloride Substances 0.000 description 1
- 239000007870 radical polymerization initiator Substances 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 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
- 208000024891 symptom Diseases 0.000 description 1
- 229960003080 taurine Drugs 0.000 description 1
- 230000004488 tear evaporation Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
Description
本発明は点眼剤に関し、更に詳細には、特定の水溶性ポリマーと油分の乳化物を含有し、ベンザルコニウム塩化物のコンタクトレンズ等への吸着を防止した点眼剤に関する。 The present invention relates to eye drops, and more particularly, to eye drops containing an emulsion of a specific water-soluble polymer and oil to prevent adsorption of benzalkonium chloride to a contact lens or the like.
コンタクトレンズ装用時においては、眼球表面の涙液層が不安定化し、涙の蒸発量が増加するため、目の乾燥感をもたらしやすい。さらにソフトコンタクトレンズにおいてはレンズからの水分の蒸発により、コンタクトレンズ自身の含水率が低下して、乾燥感が高まる。また、コンタクトレンズの装用によるレンズの動きやエッジの感覚、含水率の低下によるソフトコンタクトレンズの形状の変化などにより、異物感が生じる。現在、これらのコンタクトレンズ使用に伴って生じる症状を緩和するために点眼剤の使用が一般的である。 When a contact lens is worn, the tear film on the surface of the eyeball becomes unstable and the amount of tear evaporation increases, which tends to cause dryness of the eyes. Furthermore, in the soft contact lens, the moisture content of the contact lens itself decreases due to the evaporation of water from the lens, and the dry feeling increases. Further, a foreign object sensation is caused by the movement of the lens and the feeling of the edge due to the wearing of the contact lens, and the change in the shape of the soft contact lens due to the decrease in the moisture content. Currently, eye drops are commonly used to alleviate the symptoms caused by the use of these contact lenses.
従来、マルチドーズタイプの点眼剤では、防腐剤としてベンザルコニウム塩化物、ベンゼトニウム塩化物、グルコン酸クロルヘキシジン等のカチオン基を有する化合物、クロロブタノール、p-アミノ安息香酸エステル及びソルビン酸などが単独で又は組み合わされて用いられている。 Conventionally, in multi-dose type eye drops, compounds having a cationic group such as benzalkonium chloride, benzethonium chloride, chlorhexidine gluconate, chlorobutanol, p-aminobenzoic acid ester and sorbic acid alone are used as preservatives. Or they are used in combination.
これらの防腐剤の中でも、特にベンザルコニウム塩化物は防腐力に優れるため点眼剤の防腐剤として汎用されている。しかし、ベンザルコニウム塩化物は、コンタクトレンズ、特にソフトコンタクトレンズとの親和性が高いために、これが配合された点眼剤をコンタクトレンズを装着したままで点眼すると、点眼剤中のベンザルコニウム塩化物がコンタクトレンズに吸着し、コンタクトレンズ中に逐次蓄積されていくことがあった。そしてこの吸着や蓄積に起因してコンタクトレンズの変質や物理的変化が生じることがあり、また、防腐剤を蓄積した状態のコンタクトレンズを長期間装用していると、眼障害をおこす可能性もあった。 Among these preservatives, in particular, benzalkonium chloride is widely used as a preservative for eye drops because of its excellent antiseptic power. However, since benzalkonium chloride has a high affinity for contact lenses, particularly soft contact lenses, when an eye drop containing the benzalkonium chloride is applied with the contact lens attached, the benzalkonium chloride in the eye drop Objects may be adsorbed to the contact lens and accumulated sequentially in the contact lens. This adhesion and accumulation may cause alteration and physical changes in the contact lens, and may cause eye damage if a contact lens with accumulated preservatives is worn for a long time. there were.
このような問題があるため、コンタクトレンズを装着したままで点眼することができ、かつ点眼剤自体の保存安定性に優れる点眼剤を得るためには、点眼剤中に含有される、例えばベンザルコニウム塩化物のようなカチオン基を有する防腐剤のコンタクトレンズへの吸着を防ぐ手段の開発が必要である。 Because of such problems, in order to obtain an eye drop that can be instilled with a contact lens attached and that is excellent in storage stability of the eye drop itself, for example, Benzalkco, which is contained in the eye drop, is used. There is a need to develop a means for preventing preservatives having cationic groups such as nium chloride from adsorbing to contact lenses.
近年では、上記手段として種々の提案がなされており、その例として、シクロデキストリンとエチレンジアミン四酢酸またはその塩とを添加する方法(特許文献1)、非イオン界面活性剤と酸性ムコ多糖類とを添加する方法(特許文献2)などが挙げられる。 In recent years, various proposals have been made as the above-mentioned means. Examples thereof include a method of adding cyclodextrin and ethylenediaminetetraacetic acid or a salt thereof (Patent Document 1), a nonionic surfactant and an acidic mucopolysaccharide. The method of adding (patent document 2) etc. is mentioned.
また、点眼剤をコンタクトレンズを装着したままで使用可能とするためには、防腐剤以外の成分のコンタクトレンズへの吸着も考慮する必要がある。
防腐剤以外の成分で吸着について配慮が必要なものとしては、ケトチフェン、脂溶性ビタミン、清涼化剤などがあげられ、これらの吸着抑制方法として、多価アルコールを配合する方法(特許文献3)、高分子化合物及び/又は非イオン性界面活性剤を配合する方法(特許文献4)、ポリオキシエチレンソルビタンエステルを配合する方法や(特許文献5)、油および乳化剤として界面活性剤、レシチンを用いて清涼化剤を水中油型エマルションの形態としたもの(特許文献6)などが知られている。
Further, in order to make it possible to use the eye drop with the contact lens attached, it is necessary to consider the adsorption of components other than the preservative to the contact lens.
Examples of ingredients other than preservatives that need to be considered for adsorption include ketotifen, fat-soluble vitamins, and refreshing agents. As a method for inhibiting these adsorption, a method of blending polyhydric alcohol (Patent Document 3), A method of blending a polymer compound and / or a nonionic surfactant (Patent Document 4), a method of blending a polyoxyethylene sorbitan ester (Patent Document 5), a surfactant and lecithin as oils and emulsifiers A cooling agent in the form of an oil-in-water emulsion (Patent Document 6) is known.
しかし、界面活性剤は、それ自身眼刺激があることから、その配合による点眼剤の安全性の低下が懸念されている。またレシチンを用いたエマルションは、耐塩性が低く配合できる成分に制限があり、例えば、前記したベンザルコニウム塩化物を配合することができないという問題があった。 However, since surfactants themselves have eye irritation, there is a concern that the safety of eye drops may be reduced due to their formulation. In addition, the emulsion using lecithin has a problem that the salt resistance is low and the components that can be blended are limited. For example, the aforementioned benzalkonium chloride cannot be blended.
従って、本発明は、コンタクトレンズ、特にソフトコンタクトレンズを装着したままで点眼が可能な、コンタクトレンズへのベンザルコニウム塩化物の吸着を抑制し、かつ刺激性等の問題のない点眼剤の提供をその課題とする。 Accordingly, the present invention provides an eye drop that can be instilled while wearing a contact lens, particularly a soft contact lens, suppresses the adsorption of benzalkonium chloride to the contact lens, and has no problems such as irritation. Is the subject.
本発明者らは上記課題を解決するために鋭意研究した結果、ヒマシ油、流動パラフィン、ラノリン、ワセリン等の油分と特定の水溶性ポリマーを乳化物とし配合することにより、コンタクトレンズに対するベンザルコニウム塩化物への吸着を抑制しうることを見出し、本発明を完成した。 As a result of diligent research to solve the above-mentioned problems, the present inventors have formulated benzalkonium for contact lenses by blending oils such as castor oil, liquid paraffin, lanolin and petrolatum with a specific water-soluble polymer as an emulsion. The inventors have found that adsorption to chloride can be suppressed and completed the present invention.
すなわち本発明は、ヒマシ油、流動パラフィン、ラノリンおよびワセリンからなる群より選ばれる油分と、2−メタクリロイルオキシエチルホスホリルコリンおよびブチル(メタ)アクリレートとの共重合体である水溶性ポリマーとを含む乳化物に、ベンザルコニウム塩化物を含有せしめたことを特徴とする点眼剤を提供するものである。 That is, the present invention is an emulsion comprising an oil selected from the group consisting of castor oil, liquid paraffin, lanolin and petrolatum, and a water-soluble polymer which is a copolymer of 2-methacryloyloxyethyl phosphorylcholine and butyl (meth) acrylate. Further, the present invention provides an eye drop characterized by containing benzalkonium chloride.
本発明の点眼剤は、ヒマシ油、流動パラフィン、ラノリンおよびワセリンからなる群より選ばれる油分と2−メタクリロイルオキシエチルホスホリルコリンとブチル(メタ)アクリレートとの共重合体である水溶性ポリマーとを乳化物の形態で配合することで、点眼剤中のベンザルコニウム塩化物がコンタクトレンズに吸着することを抑制するものであり、コンタクトレンズを装着した状態で点眼を行っても問題が生じないものである。 The eye drop of the present invention is an emulsion of an oil selected from the group consisting of castor oil, liquid paraffin, lanolin and petrolatum, and a water-soluble polymer which is a copolymer of 2-methacryloyloxyethyl phosphorylcholine and butyl (meth) acrylate. By blending in the form of, the benzalkonium chloride in the eye drop is suppressed from adsorbing to the contact lens, and there is no problem even if the eye drop is performed with the contact lens attached. .
また、本発明の点眼剤は配合できる成分に特に制限がないことから、あらゆる有効成分を目的に合わせて多種類配合した点眼薬とすることもできる。 Moreover, since there are no particular limitations on the components that can be blended in the eye drop of the present invention, it is also possible to make eye drops in which various active ingredients are blended according to the purpose.
本発明の点眼剤に含有されるヒマシ油、流動パラフィン、ラノリンまたはワセリン等の油分(以下、「油分」という)は、前記したように従来から人工涙液等の点眼剤の成分として利用されているものであり、何れも公知のものを使用できる。より具体的には、ヒマシ油、流動パラフィン、ラノリンおよびワセリンは、日本薬局方適合品であればいずれも使用することができる。 Oils such as castor oil, liquid paraffin, lanolin and petrolatum (hereinafter referred to as “oil”) contained in the eye drops of the present invention have been conventionally used as components of eye drops such as artificial tears as described above. Any known one can be used. More specifically, any of castor oil, liquid paraffin, lanolin and petrolatum can be used as long as they are compatible with the Japanese Pharmacopoeia.
また、本発明に配合される、2−メタクリロイルオキシエチルホスホリルコリン(以下、「MPC」という)とブチル(メタ)アクリレートとの共重合体である水溶性ポリマー(以下、「MPCポリマー」という)は、MPCを例えば、WO99/26637等に記載の方法により重合させたものである。すなわち、2-メタクリロイルオキシエチルホスホリルコリン単量体とブチル(メタ)アクリレート単量体とをラジカル重合開始剤の存在下、脱気条件下、あるいは窒素ガス、アルゴンガス、ヘリウムガス、二酸化炭素ガス等の不活性ガス置換または雰囲気下で、水、メタノール、エタノール等の溶媒中で加熱あるいは光を照射することにより重合させ、製造することができる。容易に入手できるMPCポリマーの例としては、リピジュア(登録商標:日油株式会社製)等を挙げることができる。また、リピジュアを含有する水溶液も日油株式会社よりリピジュア−PMB等の商品名で市販されているのでこれを用いても良い。 Further, a water-soluble polymer (hereinafter referred to as “MPC polymer”), which is a copolymer of 2-methacryloyloxyethyl phosphorylcholine (hereinafter referred to as “MPC”) and butyl (meth) acrylate, blended in the present invention, MPC is polymerized by the method described in WO99 / 26637, for example. That is, 2-methacryloyloxyethyl phosphorylcholine monomer and butyl (meth) acrylate monomer in the presence of a radical polymerization initiator, degassing conditions, or nitrogen gas, argon gas, helium gas, carbon dioxide gas, etc. It can be produced by polymerization by heating or irradiating light in a solvent such as water, methanol, ethanol under an inert gas substitution or atmosphere. Examples of easily available MPC polymers include Lipidure (registered trademark: manufactured by NOF Corporation). Moreover, since the aqueous solution containing a lipid is also marketed by the brand name, such as lipid-PMB, from NOF Corporation, you may use this.
上記油分およびMPCポリマーを乳化物の形態とするには、乳化剤を使用することなく、これら両成分を常法に従い激しく撹拌すれば良い。すなわち、MPCポリマーを水等の溶媒に溶解させた溶液を加温し、これに油分を添加した後、激しく攪拌すれば良い。なお、MPCポリマーを用いて乳化物を得るための方法の一例は、特開平10−109029号公報にも記載されているので、この記載を基に乳化物を得ても良い。 In order to make the oil and MPC polymer into the form of an emulsion, these components may be vigorously stirred according to a conventional method without using an emulsifier. That is, a solution in which MPC polymer is dissolved in a solvent such as water is heated, and an oil component is added thereto, and then vigorously stirred. In addition, since an example of the method for obtaining an emulsion using MPC polymer is described also in Unexamined-Japanese-Patent No. 10-109029, you may obtain an emulsion based on this description.
より具体的に上記乳化物を得るための一例を示せば次の通りである。まず、MPCポリマーを0.0001〜40質量%(以下、単に「%」という)、好ましくは0.001〜10%、更に好ましくは0.01〜5%溶解した水溶液を、60〜90℃、好ましくは65〜75℃に加温する。次に、それに油分を前記MPCポリマー1質量部に対して0.01〜5質量部、好ましくは0.1〜1質量部添加した後、マグネチックスターラーまたはホモジナイザー(ヒスコトロン(商品名):日立製作所製)などで攪拌して予備乳化物を得る。更に、この予備乳化物を、高圧ホモジナイザー(PANDA 2K型:Niro Soavi S. p. A製又はマイクロフルイダイザー:Microfluidics製)等を用い、60MPa以上、好ましくは、80MPa以上で、1〜50回程度、好ましくは、3〜30回程度処理することにより、目的の乳化物を微細乳化物として得ることができる。この微細乳化物の平均粒子径は50〜300nm、好ましくは200nm程度である。 A more specific example for obtaining the emulsion is as follows. First, an aqueous solution in which an MPC polymer is dissolved in an amount of 0.0001 to 40% by mass (hereinafter simply referred to as “%”), preferably 0.001 to 10%, more preferably 0.01 to 5%, Preferably it heats to 65-75 degreeC. Next, oil is added to 0.01-5 parts by mass, preferably 0.1-1 part by mass with respect to 1 part by mass of the MPC polymer, and then a magnetic stirrer or homogenizer (Hiscotron (trade name): Hitachi, Ltd.) Etc.) to obtain a preliminary emulsion. Further, the pre-emulsified product is used at a pressure of 60 MPa or more, preferably about 80 MPa or more and about 1 to 50 times using a high-pressure homogenizer (PANDA 2K type: manufactured by Niro Soavi S. p. A or microfluidizer: manufactured by Microfluidics) Preferably, the target emulsion can be obtained as a fine emulsion by treating about 3 to 30 times. The average particle size of the fine emulsion is 50 to 300 nm, preferably about 200 nm.
本発明における上記乳化物の含有量は特に限定されないが、例えば、点眼剤全体に対し、油分の含有量が0.001〜10%、好ましくは0.01〜1%となるように配合すれば良い。0.001%未満であると十分な効果が得られない恐れがあり、10%を超えると使用感が悪くなる、製剤安定性が低下するなどの問題が生じる。また、MPCポリマーの含有量も点眼剤全体に対し、0.0001〜40%、好ましくは0.001〜10%、更に好ましくは0.01〜5%となるように配合すれば良い。0.0001%未満であると十分な効果が得られない恐れがあり、40%を超えると使用感が悪くなる恐れがある。 The content of the emulsion in the present invention is not particularly limited. For example, if the oil content is 0.001 to 10%, preferably 0.01 to 1%, based on the whole eye drop. good. If it is less than 0.001%, sufficient effects may not be obtained, and if it exceeds 10%, the feeling in use becomes worse and the stability of the preparation decreases. Moreover, what is necessary is just to mix | blend MPC polymer content so that it may become 0.0001 to 40% with respect to the whole eyedrops, Preferably it is 0.001 to 10%, More preferably, it is 0.01 to 5%. If it is less than 0.0001%, a sufficient effect may not be obtained, and if it exceeds 40%, the usability may be deteriorated.
本発明におけるベンザルコニウム塩化物の含有量は特に制限されないが、点眼剤全体の0.001〜0.1質量/容量%であり、好ましくは0.005〜0.02質量/容量%である。0.001質量/容量%未満であると防腐剤による防腐作用が不十分となり、0.1質量/容量%を超えると点眼剤の点眼適用時の眼刺激が生じて使用感を損ねる場合がある。 The content of benzalkonium chloride in the present invention is not particularly limited, but is 0.001 to 0.1% by mass / volume%, preferably 0.005 to 0.02% by mass / volume% of the whole eye drop. . If the amount is less than 0.001 mass / volume%, the antiseptic action by the preservative is insufficient, and if it exceeds 0.1 mass / volume%, eye irritation may occur when the eye drops are applied, and the feeling of use may be impaired. .
本発明の点眼剤は、上記乳化物とベンザルコニウム塩化物を、常法に従い、適当な溶媒等に加え、pHや浸透圧等を調整して製剤化し、更に滅菌等を行うことにより製造される。 The eye drop of the present invention is produced by adding the above emulsion and benzalkonium chloride to a suitable solvent, etc. according to a conventional method, adjusting the pH, osmotic pressure, etc., and further sterilizing. The
また、本発明の点眼剤の製造においては、上記乳化物やベンザルコニウム塩化物の他に、従来公知の任意成分を配合することができる。このような任意成分としては塩化ナトリウム、塩化カリウム、塩化カルシウム、塩化マグネシウム等の無機塩類、ヒドロキシエチルセルロース等の粘ちょう化剤、ブドウ糖などの糖類、グリセリンなどの多価アルコール類、塩酸ナファゾリンなどの充血除去成分、ネオスチグミンメチル硫酸塩などのピント調節薬、イプシロンーアミノカプロン酸などの抗炎症成分、マレイン酸クロルフェニラミンなどの抗ヒスタミン薬、シアノコバラミン、ピリドキシン塩酸塩などのビタミン類、タウリン、アスパラギン酸塩類などアミノ酸類、スルファメトキサゾールなどのサルファ剤、クロモグリク酸塩類などの抗アレルギー成分、ポリオキシエチレンソルビタンモノオレエートなどの界面活性剤、メントール、カンフルなどの精油、ホウ酸、クエン酸塩類などの緩衝剤、エデト酸塩類などの安定剤等が挙げられる。 Moreover, in manufacture of the eye drop of this invention, conventionally well-known arbitrary components can be mix | blended other than the said emulsion and benzalkonium chloride. Examples of such optional components include inorganic salts such as sodium chloride, potassium chloride, calcium chloride, and magnesium chloride; thickeners such as hydroxyethyl cellulose; sugars such as glucose; polyhydric alcohols such as glycerin; and hyperemia such as naphazoline hydrochloride. Removal components, focus regulators such as neostigmine methylsulfate, anti-inflammatory components such as epsilon-aminocaproic acid, antihistamines such as chlorpheniramine maleate, vitamins such as cyanocobalamin and pyridoxine hydrochloride, taurine and aspartate Amino acids, sulfa drugs such as sulfamethoxazole, antiallergic ingredients such as cromoglycates, surfactants such as polyoxyethylene sorbitan monooleate, essential oils such as menthol and camphor, boric acid, citric acid Buffers such as class, stabilizers such as edetate salts.
斯くして得られる本発明の点眼剤は、コンタクトレンズへの吸着を防止しうる状態で防腐剤であるベンザルコニウム塩化物の配合ができるため、従来型のマルチドーズタイプの点眼薬等として目の各種疾患の治療に用いることができる。また、配合できる成分に特に制限がないことから、涙液中の塩の比率、涙液の物性に合わせて無機塩類等を配合した人工涙液、各種有効成分を目的に合わせて多種類配合した一般点眼薬とすることができる。 The thus obtained eye drop of the present invention can contain benzalkonium chloride as a preservative in a state where it can be prevented from adsorbing to a contact lens, so that it can be used as a conventional multi-dose type eye drop. It can be used for the treatment of various diseases. In addition, since there are no particular restrictions on the components that can be blended, artificial tears containing inorganic salts etc. according to the ratio of the salt in tears, the physical properties of tears, and various active ingredients were blended according to the purpose. It can be a general eye drop.
以下、本発明を製造例、実施例および試験例を挙げて詳細に説明するが、本発明はこれらの実施例に何ら限定されるものではない。 Hereinafter, the present invention will be described in detail with reference to production examples, examples and test examples, but the present invention is not limited to these examples.
製 造 例 1
乳化物1の調製:
2−メタクリロイルオキシエチルホスホリルコリンとブチル(メタ)アクリレートの共重合体である水溶性ポリマーの5%水溶液(リピジュア−PMB(商品名):日油株式会社製)の200重量部を約70℃に加温した。これにヒマシ油(日本薬局方適合品)5重量部を添加し、マグネチックスターラーで約10分間激しく撹拌し、予備乳化物を得た。この予備乳化物を卓上型高圧ホモジナイザー(PANDA 2K型:Niro Soavi S. p. A製)を用い、約120Mpaの圧力で20回処理し、微細な乳化物とした。この乳化物の粒子径を粒度分布測定装置(NICOMP380ZLS:Particle Sizing System社製)で測定したところ、その平均粒子径は210nmであった。
Manufacturing example 1
Preparation of Emulsion 1:
200 parts by weight of a 5% aqueous solution (Lipidure-PMB (trade name) manufactured by NOF Corporation) of a water-soluble polymer that is a copolymer of 2-methacryloyloxyethyl phosphorylcholine and butyl (meth) acrylate was added to about 70 ° C. Warm up. To this was added 5 parts by weight of castor oil (Japanese Pharmacopoeia compatible product) and stirred vigorously with a magnetic stirrer for about 10 minutes to obtain a preliminary emulsion. This pre-emulsion was processed 20 times at a pressure of about 120 Mpa using a desktop type high-pressure homogenizer (PANDA 2K type: manufactured by Niro Soavi S. p. A) to obtain a fine emulsion. When the particle size of this emulsion was measured with a particle size distribution analyzer (NICOMP380ZLS: manufactured by Particle Sizing System), the average particle size was 210 nm.
製 造 例 2
乳化物2の調製:
2−メタクリロイルオキシエチルホスホリルコリンとブチル(メタ)アクリレートの共重合体である水溶性ポリマーの5%水溶液(リピジュア−PMB(商品名):日油株式会社製)の200重量部に流動パラフィン(日本薬局方適合品)5重量部を添加し、マグネチックスターラーで約10分間激しく撹拌し、予備乳化物を得た。この予備乳化物を高圧乳化機(マイクロフルイダイザー:Microfluidics製)を用い、約190Mpaの圧力で5回処理し、微細な乳化物とした。この乳化物の粒子径を粒度分布測定装置(NICOMP380ZLS:Particle Sizing System社製)で測定したところ、その平均粒子径は206nmであった。
Manufacturing example 2
Preparation of Emulsion 2:
Liquid paraffin (Nippon Pharmacy) in 200 parts by weight of 5% aqueous solution of water-soluble polymer (Lipidure-PMB (trade name) manufactured by NOF Corporation), which is a copolymer of 2-methacryloyloxyethyl phosphorylcholine and butyl (meth) acrylate How to fit) 5 parts by weight were added and vigorously stirred with a magnetic stirrer for about 10 minutes to obtain a preliminary emulsion. This pre-emulsion was processed five times at a pressure of about 190 Mpa using a high-pressure emulsifier (Microfluidizer: manufactured by Microfluidics) to obtain a fine emulsion. When the particle size of this emulsion was measured with a particle size distribution measuring device (NICOMP380ZLS: manufactured by Particle Sizing System), the average particle size was 206 nm.
実 施 例 1
点眼剤の調製:
生理食塩水85mLに、製造例1で調製した乳化物1を2,050mgおよび濃ベンザルコニウム塩化物液50(カオウK.K.社製)を10mg溶解し、更に、生理食塩水を加えて全量を100mLとして点眼剤を調製した。その後、ろ過滅菌を行い、無菌の点眼剤とした。
Example 1
Preparation of eye drops:
In 85 mL of physiological saline, 2,050 mg of Emulsion 1 prepared in Production Example 1 and 10 mg of concentrated benzalkonium chloride solution 50 (manufactured by Kao K.K.) were dissolved, and then physiological saline was added. Eye drops were prepared with a total volume of 100 mL. Thereafter, the solution was sterilized by filtration to obtain a sterile eye drop.
実 施 例 2
点眼剤の調製:
生理食塩水85mLに、製造例2で調製した乳化物2を2,050mgおよび濃ベンザルコニウム塩化物液50(カオウK.K.社製)を10mg溶解し、更に、生理食塩水を加えて全量を100mLとして点眼剤を調製した。その後、ろ過滅菌を行い、無菌の点眼剤とした。
Example 2
Preparation of eye drops:
In 85 mL of physiological saline, 2,050 mg of Emulsion 2 prepared in Production Example 2 and 10 mg of concentrated benzalkonium chloride solution 50 (manufactured by Kao K.K.) were dissolved, and then physiological saline was added. Eye drops were prepared with a total volume of 100 mL. Thereafter, the solution was sterilized by filtration to obtain a sterile eye drop.
比 較 例 1
点眼剤の調製:
生理食塩水85mLに、MPCポリマー(リピジュア−PMB(商品名):日油株式会社製)を2,000mg、濃ベンザルコニウム塩化物液50(カオウK.K.社製 )を10mg溶解し、更に、生理食塩水を加えて全量を100mLとして点眼剤を調製した。その後ろ過滅菌を行い、無菌の点眼剤とした。
Comparative Example 1
Preparation of eye drops:
In 85 mL of physiological saline, 2,000 mg of MPC polymer (Lipidure-PMB (trade name): NOF Corporation) and 10 mg of concentrated benzalkonium chloride solution 50 (manufactured by Kao K.K.) were dissolved. Further, an eye drop was prepared by adding physiological saline to a total volume of 100 mL. Thereafter, the solution was sterilized by filtration to obtain a sterile eye drop.
比 較 例 2
点眼剤の調製:
生理食塩水85mLに、濃ベンザルコニウム塩化物液50(カオウK.K.社製 )を10mg溶解し、更に、生理食塩水を加えて全量を100mLとして点眼剤を調製した。その後ろ過滅菌を行い、無菌の点眼剤とした。
Comparative Example 2
Preparation of eye drops:
An eye drop was prepared by dissolving 10 mg of concentrated benzalkonium chloride solution 50 (manufactured by Kao K.K.) in 85 mL of physiological saline and further adding physiological saline to make a total volume of 100 mL. Thereafter, the solution was sterilized by filtration to obtain a sterile eye drop.
比 較 例 3
点眼剤の調製:
生理食塩水85mLに、濃ベンザルコニウム塩化物液50(カオウK.K.社製 )を10mg溶解し、更に、生理食塩水を加えて全量を100mLとして点眼剤を調製した。その後ろ過滅菌を行い、無菌の点眼剤とした。
Comparative Example 3
Preparation of eye drops:
An eye drop was prepared by dissolving 10 mg of concentrated benzalkonium chloride solution 50 (manufactured by Kao K.K.) in 85 mL of physiological saline and further adding physiological saline to make a total volume of 100 mL. Thereafter, the solution was sterilized by filtration to obtain a sterile eye drop.
試 験 例 1
ベンザルコニウム塩化物の吸着抑制試験法:
50mLの遠沈管に実施例1、比較例1および比較例2の点眼剤をそれぞれ2mLずつとり、これに1枚のソフトコンタクトレンズを浸漬し、35℃の恒温槽で24時間静置した。その後、ソフトコンタクトレンズを取り出し、この点眼剤中に存在するベンザルコニウム塩化物の濃度をHPLCにて定量し、下記式により吸着率を算出した。
吸着率(%)=(A−B)/A×100
A:サンプル溶液中のベンザルコニウム塩化物濃度
B:浸漬試験後のサンプル溶液中のベンザルコニウム塩化物濃度
Test example 1
Benzalkonium chloride adsorption inhibition test method:
2 mL each of the eye drops of Example 1, Comparative Example 1 and Comparative Example 2 were placed in a 50 mL centrifuge tube, and one piece of soft contact lens was immersed therein and allowed to stand in a thermostatic bath at 35 ° C. for 24 hours. Thereafter, the soft contact lens was taken out, the concentration of benzalkonium chloride present in this eye drop was quantified by HPLC, and the adsorption rate was calculated by the following formula.
Adsorption rate (%) = (A−B) / A × 100
A: Benzalkonium chloride concentration in sample solution
B: Benzalkonium chloride concentration in sample solution after immersion test
なお、ソフトコンタクトレンズとして、FDA分類IV(高含水イオン性)のフォーカス2ウィークレンズ(チバビジョン製)を用いた。 As a soft contact lens, an FDA classification IV (high water content ionic) Focus 2 week lens (manufactured by Ciba Vision) was used.
表1に結果を示す。
表1の結果より、ベンザルコニウム塩化物を配合する溶液にヒマシ油、流動パラフィン、ラノリン、またはワセリンの油分と特定の水溶性ポリマーとを乳化物とし配合すると、ソフトコンタクトレンズへのベンザルコニウム塩化物の吸着が抑制されることが認められた。 From the results in Table 1, when a solution containing benzalkonium chloride is mixed with castor oil, liquid paraffin, lanolin, or petroleum jelly oil and a specific water-soluble polymer as an emulsion, benzalkonium for soft contact lenses is incorporated. It was observed that chloride adsorption was suppressed.
試 験 例 2
ベンザルコニウム塩化物の吸着抑制試験法:
50mLの遠沈管に実施例2、比較例3の点眼剤をそれぞれ2mLずつとり、これに1枚のソフトコンタクトレンズを浸漬し、35℃の恒温槽で24時間静置した。その後、ソフトコンタクトレンズを取り出し、この点眼剤中に存在するベンザルコニウム塩化物の濃度をHPLCにて定量し、下記式により吸着率を算出した。
吸着率(%)=(A−B)/A×100
A:サンプル溶液中のベンザルコニウム塩化物濃度
B:浸漬試験後のサンプル溶液中のベンザルコニウム塩化物濃度
Test example 2
Benzalkonium chloride adsorption inhibition test method:
2 mL each of the eye drops of Example 2 and Comparative Example 3 were placed in a 50 mL centrifuge tube, and one soft contact lens was immersed therein and allowed to stand for 24 hours in a 35 ° C. constant temperature bath. Thereafter, the soft contact lens was taken out, the concentration of benzalkonium chloride present in this eye drop was quantified by HPLC, and the adsorption rate was calculated by the following formula.
Adsorption rate (%) = (A−B) / A × 100
A: Benzalkonium chloride concentration in sample solution
B: Benzalkonium chloride concentration in sample solution after immersion test
なお、ソフトコンタクトレンズとして、FDA分類IV(高含水イオン性)のフォーカス2ウィークレンズ(チバビジョン製)を用いた。 As a soft contact lens, an FDA classification IV (high water content ionic) Focus 2 week lens (manufactured by Ciba Vision) was used.
表2に結果を示す。
表2の結果より、ベンザルコニウム塩化物を配合する溶液にヒマシ油、流動パラフィン、ラノリン、またはワセリンの油分と特定の水溶性ポリマーとを乳化物とし配合すると、ソフトコンタクトレンズへのベンザルコニウム塩化物の吸着が抑制されることが認められた。 From the results in Table 2, when a solution containing benzalkonium chloride is blended with castor oil, liquid paraffin, lanolin, or petroleum jelly oil and a specific water-soluble polymer as an emulsion, benzalkonium is added to the soft contact lens. It was observed that chloride adsorption was suppressed.
本願発明の点眼剤は、コンタクトレンズ、特にソフトコンタクトレンズへのベンザルコニウム塩化物の吸着を抑制することが可能であるため、コンタクトレンズを装着したまま点眼できる点眼剤として利用可能である。また、製剤自体が安定であるため、あらゆる有効成分を目的に合わせて多種類配合した点眼薬とすることができる。 Since the ophthalmic solution of the present invention can suppress the adsorption of benzalkonium chloride to a contact lens, particularly a soft contact lens, it can be used as an ophthalmic solution that can be instilled while wearing the contact lens. In addition, since the preparation itself is stable, it can be an eye drop in which various active ingredients are blended in accordance with the purpose.
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WO2015029717A1 (en) | 2013-08-30 | 2015-03-05 | 日油株式会社 | Ophthalmic solution |
JP2015147760A (en) * | 2014-01-08 | 2015-08-20 | 日油株式会社 | eye drops |
WO2016104704A1 (en) * | 2014-12-25 | 2016-06-30 | 参天製薬株式会社 | Aqueous ophthalmic solution |
JP2019214525A (en) * | 2018-06-12 | 2019-12-19 | ライオン株式会社 | Aqueous ophthalmic composition |
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US10471171B2 (en) | 2013-08-30 | 2019-11-12 | Nof Corporation | Ophthalmic solution |
KR20160048189A (en) | 2013-08-30 | 2016-05-03 | 니치유 가부시키가이샤 | Ophthalmic solution |
WO2015029717A1 (en) | 2013-08-30 | 2015-03-05 | 日油株式会社 | Ophthalmic solution |
JP2015147760A (en) * | 2014-01-08 | 2015-08-20 | 日油株式会社 | eye drops |
WO2016104704A1 (en) * | 2014-12-25 | 2016-06-30 | 参天製薬株式会社 | Aqueous ophthalmic solution |
US10278985B2 (en) | 2014-12-25 | 2019-05-07 | Santen Pharmaceutical Co., Ltd. | Aqueous ophthalmic solution |
JP2016210759A (en) * | 2014-12-25 | 2016-12-15 | 参天製薬株式会社 | Aqueous eye drop |
EA034517B1 (en) * | 2014-12-25 | 2020-02-17 | Сантен Фармасьютикал Ко., Лтд. | Aqueous ophthalmic solution |
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JP2021008513A (en) * | 2014-12-25 | 2021-01-28 | 参天製薬株式会社 | Aqueous eye drop |
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JP7139703B2 (en) | 2018-06-12 | 2022-09-21 | ライオン株式会社 | Aqueous ophthalmic composition |
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