JP5981488B2 - Water-containing patch - Google Patents
Water-containing patch Download PDFInfo
- Publication number
- JP5981488B2 JP5981488B2 JP2014116589A JP2014116589A JP5981488B2 JP 5981488 B2 JP5981488 B2 JP 5981488B2 JP 2014116589 A JP2014116589 A JP 2014116589A JP 2014116589 A JP2014116589 A JP 2014116589A JP 5981488 B2 JP5981488 B2 JP 5981488B2
- Authority
- JP
- Japan
- Prior art keywords
- adhesive layer
- patch
- ethylene oxide
- hlb value
- active ingredient
- 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.)
- Active
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 title claims description 17
- -1 polyoxyethylene Polymers 0.000 claims description 39
- 239000004480 active ingredient Substances 0.000 claims description 25
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims description 24
- 239000002736 nonionic surfactant Substances 0.000 claims description 22
- 239000004820 Pressure-sensitive adhesive Substances 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 18
- 239000010410 layer Substances 0.000 claims description 17
- 239000012790 adhesive layer Substances 0.000 claims description 10
- 239000012453 solvate Substances 0.000 claims description 10
- 229960002373 loxoprofen Drugs 0.000 claims description 9
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 8
- BAZQYVYVKYOAGO-UHFFFAOYSA-M loxoprofen sodium hydrate Chemical compound O.O.[Na+].C1=CC(C(C([O-])=O)C)=CC=C1CC1C(=O)CCC1 BAZQYVYVKYOAGO-UHFFFAOYSA-M 0.000 claims description 8
- 239000004359 castor oil Substances 0.000 claims description 5
- 235000019438 castor oil Nutrition 0.000 claims description 5
- 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 description 5
- 229920000259 polyoxyethylene lauryl ether Polymers 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 description 19
- 239000000126 substance Substances 0.000 description 11
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 239000004094 surface-active agent Substances 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 238000013329 compounding Methods 0.000 description 5
- 150000003997 cyclic ketones Chemical group 0.000 description 5
- 229920000139 polyethylene terephthalate Polymers 0.000 description 5
- 239000005020 polyethylene terephthalate Substances 0.000 description 5
- 159000000000 sodium salts Chemical class 0.000 description 5
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 4
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- 229920002125 Sokalan® Polymers 0.000 description 4
- 239000000853 adhesive Substances 0.000 description 4
- 230000001070 adhesive effect Effects 0.000 description 4
- 229910052783 alkali metal Inorganic materials 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 235000011187 glycerol Nutrition 0.000 description 4
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- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 229920005989 resin Polymers 0.000 description 4
- 239000011347 resin Substances 0.000 description 4
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 4
- MGSRCZKZVOBKFT-UHFFFAOYSA-N thymol Chemical compound CC(C)C1=CC=C(C)C=C1O MGSRCZKZVOBKFT-UHFFFAOYSA-N 0.000 description 4
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 3
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 3
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 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
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 3
- 229910052782 aluminium Inorganic materials 0.000 description 3
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 3
- 239000003963 antioxidant agent Substances 0.000 description 3
- 230000003078 antioxidant effect Effects 0.000 description 3
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- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 229920001577 copolymer Polymers 0.000 description 3
- 238000004132 cross linking Methods 0.000 description 3
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- 239000000975 dye Substances 0.000 description 3
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- 125000000962 organic group Chemical group 0.000 description 3
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- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 2
- 239000005977 Ethylene Substances 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 239000004743 Polypropylene Substances 0.000 description 2
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 2
- 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 2
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- 239000002253 acid Substances 0.000 description 2
- BWZOPYPOZJBVLQ-UHFFFAOYSA-K aluminium glycinate Chemical compound O[Al+]O.NCC([O-])=O BWZOPYPOZJBVLQ-UHFFFAOYSA-K 0.000 description 2
- DIZPMCHEQGEION-UHFFFAOYSA-H aluminium sulfate (anhydrous) Chemical compound [Al+3].[Al+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O DIZPMCHEQGEION-UHFFFAOYSA-H 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 229940024546 aluminum hydroxide gel Drugs 0.000 description 2
- SMYKVLBUSSNXMV-UHFFFAOYSA-K aluminum;trihydroxide;hydrate Chemical compound O.[OH-].[OH-].[OH-].[Al+3] SMYKVLBUSSNXMV-UHFFFAOYSA-K 0.000 description 2
- 235000019437 butane-1,3-diol Nutrition 0.000 description 2
- 159000000007 calcium salts Chemical class 0.000 description 2
- 229940015826 dihydroxyaluminum aminoacetate Drugs 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 239000004744 fabric Substances 0.000 description 2
- 235000019256 formaldehyde Nutrition 0.000 description 2
- 229940079826 hydrogen sulfite Drugs 0.000 description 2
- 229940041616 menthol Drugs 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000003002 pH adjusting agent Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
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- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
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- 235000010265 sodium sulphite Nutrition 0.000 description 2
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- 229920003169 water-soluble polymer Polymers 0.000 description 2
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- 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
- 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
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- FFJCNSLCJOQHKM-CLFAGFIQSA-N (z)-1-[(z)-octadec-9-enoxy]octadec-9-ene Chemical compound CCCCCCCC\C=C/CCCCCCCCOCCCCCCCC\C=C/CCCCCCCC FFJCNSLCJOQHKM-CLFAGFIQSA-N 0.000 description 1
- YHMYGUUIMTVXNW-UHFFFAOYSA-N 1,3-dihydrobenzimidazole-2-thione Chemical compound C1=CC=C2NC(S)=NC2=C1 YHMYGUUIMTVXNW-UHFFFAOYSA-N 0.000 description 1
- LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical compound OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 description 1
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- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 1
- SPSPIUSUWPLVKD-UHFFFAOYSA-N 2,3-dibutyl-6-methylphenol Chemical compound CCCCC1=CC=C(C)C(O)=C1CCCC SPSPIUSUWPLVKD-UHFFFAOYSA-N 0.000 description 1
- ZRPBKKRIJQSQIF-UHFFFAOYSA-N 2-hydroxy-2-(5-methyl-2-propan-2-ylcyclohexyl)propanoic acid Chemical compound CC(C)C1CCC(C)CC1C(C)(O)C(O)=O ZRPBKKRIJQSQIF-UHFFFAOYSA-N 0.000 description 1
- LTPZLDNFECOIQY-UHFFFAOYSA-N 2-methyl-3-(1-methyl-4-propan-2-ylcyclohexyl)oxypropane-1,2-diol Chemical compound CC(C)C1CCC(C)(OCC(C)(O)CO)CC1 LTPZLDNFECOIQY-UHFFFAOYSA-N 0.000 description 1
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- WOWHHFRSBJGXCM-UHFFFAOYSA-M cetyltrimethylammonium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+](C)(C)C WOWHHFRSBJGXCM-UHFFFAOYSA-M 0.000 description 1
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- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 150000004683 dihydrates Chemical class 0.000 description 1
- LVTYICIALWPMFW-UHFFFAOYSA-N diisopropanolamine Chemical compound CC(O)CNCC(C)O LVTYICIALWPMFW-UHFFFAOYSA-N 0.000 description 1
- 229940043276 diisopropanolamine Drugs 0.000 description 1
- 235000019329 dioctyl sodium sulphosuccinate Nutrition 0.000 description 1
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 description 1
- YHAIUSTWZPMYGG-UHFFFAOYSA-L disodium;2,2-dioctyl-3-sulfobutanedioate Chemical compound [Na+].[Na+].CCCCCCCCC(C([O-])=O)(C(C([O-])=O)S(O)(=O)=O)CCCCCCCC YHAIUSTWZPMYGG-UHFFFAOYSA-L 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- YRIUSKIDOIARQF-UHFFFAOYSA-N dodecyl benzenesulfonate Chemical compound CCCCCCCCCCCCOS(=O)(=O)C1=CC=CC=C1 YRIUSKIDOIARQF-UHFFFAOYSA-N 0.000 description 1
- 229940071161 dodecylbenzenesulfonate Drugs 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 235000010985 glycerol esters of wood rosin Nutrition 0.000 description 1
- 229940075529 glyceryl stearate Drugs 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 229920006270 hydrocarbon resin Polymers 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 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
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- NFLGAXVYCFJBMK-UHFFFAOYSA-N isomenthone Natural products CC(C)C1CCC(C)CC1=O NFLGAXVYCFJBMK-UHFFFAOYSA-N 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- TYQCGQRIZGCHNB-JLAZNSOCSA-N l-ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(O)=C(O)C1=O TYQCGQRIZGCHNB-JLAZNSOCSA-N 0.000 description 1
- 238000010030 laminating Methods 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000845 maltitol Substances 0.000 description 1
- 235000010449 maltitol Nutrition 0.000 description 1
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
- 229940035436 maltitol Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000003973 paint Substances 0.000 description 1
- 239000002540 palm oil Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 229920001495 poly(sodium acrylate) polymer Polymers 0.000 description 1
- 229920001083 polybutene Polymers 0.000 description 1
- 229920001748 polybutylene Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229920000166 polytrimethylene carbonate Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- RUOJZAUFBMNUDX-UHFFFAOYSA-N propylene carbonate Chemical compound CC1COC(=O)O1 RUOJZAUFBMNUDX-UHFFFAOYSA-N 0.000 description 1
- 229960004063 propylene glycol Drugs 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 150000004040 pyrrolidinones Chemical class 0.000 description 1
- 239000002964 rayon Substances 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 229910001388 sodium aluminate Inorganic materials 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- NNMHYFLPFNGQFZ-UHFFFAOYSA-M sodium polyacrylate Chemical compound [Na+].[O-]C(=O)C=C NNMHYFLPFNGQFZ-UHFFFAOYSA-M 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 235000011071 sorbitan monopalmitate Nutrition 0.000 description 1
- 239000001570 sorbitan monopalmitate Substances 0.000 description 1
- 229940031953 sorbitan monopalmitate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 150000003505 terpenes Chemical class 0.000 description 1
- 235000007586 terpenes Nutrition 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- 229940042585 tocopherol acetate Drugs 0.000 description 1
- 239000002759 woven fabric Substances 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
- A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/12—Ketones
- A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2121/00—Preparations for use in therapy
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Dermatology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
本発明は、含水系貼付剤に関する。 The present invention relates to a hydrous patch.
近年、薬物の経口投与、注射による静脈投与等に代わり、経皮投与のため、粘着剤に有効成分を配合した粘着剤層が支持体上に位置する貼付剤がさかんに開発されている。貼付剤は、皮膚に貼付してから剥がすまでの間、長時間に亘って略一定量の有効成分を経皮吸収させることができる点で有用である。 In recent years, a patch in which an adhesive layer containing an active ingredient in an adhesive is positioned on a support has been developed for transdermal administration instead of oral administration of drugs and intravenous administration by injection. The patch is useful in that it can percutaneously absorb a substantially constant amount of the active ingredient over a long period of time from when it is applied to the skin until it is peeled off.
一方、貼付剤の粘着剤層には、有効成分の他にも、粘着剤を始めとする種々の成分が含まれており、これにより、貼付剤中の有効成分は経時的に劣化しやすく、その安定性を向上することが重要である。 On the other hand, the adhesive layer of the patch contains various components including an adhesive in addition to the active ingredient, whereby the active ingredient in the patch is likely to deteriorate over time, It is important to improve its stability.
貼付剤には、水を含有する含水系貼付剤(パップ剤)、及び非水系貼付剤(テープ剤、プラスター剤等)の二つのタイプがある。このうち、非水系貼付剤については、2−メルカプトベンズイミダゾール等の抗酸化剤を用いることで、有効成分の安定性を向上しうることが示唆されている(特許文献1)。 There are two types of patches: water-containing patches (paps) containing water and non-aqueous patches (tapes, plasters, etc.). Among these, for non-aqueous patches, it has been suggested that the stability of active ingredients can be improved by using an antioxidant such as 2-mercaptobenzimidazole (Patent Document 1).
しかし、含水系貼付剤では、粘着剤層に更に水が含まれていることから、非水系貼付剤とは異なる観点からの有効成分の安定性向上が必要と考えられる。また、有効成分の分解は、その有効成分によって異なるため、安定性向上に必要な対策も有効成分ごとに検討する必要がある。 However, in the water-containing patch, since the adhesive layer further contains water, it is considered necessary to improve the stability of the active ingredient from a viewpoint different from that of the non-aqueous patch. In addition, since the decomposition of the active ingredient varies depending on the active ingredient, it is necessary to examine measures necessary for improving the stability for each active ingredient.
本発明は、以上の実情に鑑みてなされたものであり、ロキソプロフェン等の所定の環状ケトン構造を有する有効成分(薬物)の安定性に優れた含水系貼付剤を提供することを目的とする。 The present invention has been made in view of the above circumstances, and an object thereof is to provide a water-containing patch excellent in the stability of an active ingredient (drug) having a predetermined cyclic ketone structure such as loxoprofen.
本発明者らは、所定の環状ケトン構造を有する有効成分の水系での反応性(分解性)が、非イオン性界面活性剤によって抑制されることを見出し、本発明を完成するに至った。具体的に、本発明は以下のものを提供する。 The present inventors have found that the reactivity (decomposability) of an active ingredient having a predetermined cyclic ketone structure in an aqueous system is suppressed by a nonionic surfactant, and have completed the present invention. Specifically, the present invention provides the following.
(1) 支持体と、この支持体上に位置する粘着剤層と、を備える含水系貼付剤であって、
前記粘着剤層は、一般式1で示される化合物、その薬理学的に許容される塩又は溶媒和物からなる有効成分と、非イオン性界面活性剤と、水と、を含有する含水系貼付剤。
(式中、nは0、1、又は2であり、Rは有機基である。)
(1) A hydrous patch comprising a support and a pressure-sensitive adhesive layer located on the support,
The pressure-sensitive adhesive layer is a hydrous patch containing an active ingredient comprising a compound represented by the general formula 1, a pharmacologically acceptable salt or solvate thereof, a nonionic surfactant, and water. Agent.
(In the formula, n is 0, 1, or 2, and R is an organic group.)
(2) 前記化合物は、ロキソプロフェンである(1)記載の含水系貼付剤。 (2) The water-containing patch according to (1), wherein the compound is loxoprofen.
(3) 前記非イオン性界面活性剤は、6.0以上9.5以下のHLB値を有する(1)又は(2)記載の含水系貼付剤。 (3) The water-based patch according to (1) or (2), wherein the nonionic surfactant has an HLB value of 6.0 or more and 9.5 or less.
(4) 前記非イオン性界面活性剤は、酸化エチレン付加型であり、酸化エチレン付加モル数が5モル以下である(1)から(3)いずれか記載の含水系貼付剤。 (4) The water-containing patch according to any one of (1) to (3), wherein the nonionic surfactant is an ethylene oxide addition type, and the number of moles of ethylene oxide added is 5 mol or less.
(5) 前記非イオン性界面活性剤は、ポリオキシエチレン硬化ヒマシ油(酸化エチレン付加モル数が5モル)、及びポリオキシエチレンラウリルエーテル(酸化エチレン付加モル数が2モル)からなる群より選ばれる1種以上である(4)記載の含水系貼付剤。 (5) The nonionic surfactant is selected from the group consisting of polyoxyethylene hydrogenated castor oil (5 moles of added ethylene oxide) and polyoxyethylene lauryl ether (2 moles of added ethylene oxide). The water-containing patch according to (4), which is one or more types.
(6) 支持体と、この支持体上に位置する粘着剤層と、を備える含水系貼付剤について、
前記粘着剤層に、一般式1で示される化合物、その薬理学的に許容される塩又は溶媒和物からなる有効成分と、水とともに、非イオン性界面活性剤を配合することで、前記化合物が一般式2又は一般式3で示される化合物へと変化することを抑制する方法。
(一般式1〜3中、nは0、1、又は2であり、Rは有機基である。)
(6) About a hydrous patch comprising a support and an adhesive layer located on the support,
In the pressure-sensitive adhesive layer, the compound represented by the general formula 1, an active ingredient comprising a pharmacologically acceptable salt or solvate thereof, and water together with a nonionic surfactant, Is a method for suppressing the change to a compound represented by Formula 2 or Formula 3.
(In general formulas 1 to 3, n is 0, 1 or 2, and R is an organic group.)
(6) 支持体と、この支持体上に位置する粘着剤層と、を備える含水系貼付剤について、
前記粘着剤層に、一般式1で示される化合物、その薬理学的に許容される塩又は溶媒和物からなる有効成分と、水とともに配合され、前記化合物が一般式2又は一般式3で示される化合物へと変化することを抑制するために用いられ、
非イオン性界面活性剤からなる製剤。
(6) About a hydrous patch comprising a support and an adhesive layer located on the support,
The pressure-sensitive adhesive layer is blended together with an active ingredient comprising a compound represented by general formula 1, a pharmacologically acceptable salt or solvate thereof, and water, and the compound is represented by general formula 2 or general formula 3. Used to suppress the change to a compound
A preparation comprising a nonionic surfactant.
本発明によれば、所定の環状ケトン構造を有する有効成分の水系での反応性が、非イオン性界面活性剤によって抑制されるため、含水系貼付剤におけるロキソプロフェン等の所定の環状ケトン構造を有する有効成分の安定性を向上することができる。 According to the present invention, since the reactivity of an active ingredient having a predetermined cyclic ketone structure in an aqueous system is suppressed by a nonionic surfactant, it has a predetermined cyclic ketone structure such as loxoprofen in a hydrous patch. The stability of the active ingredient can be improved.
以下、本発明の実施形態について説明するが、本発明を限定する趣旨ではない。 Hereinafter, although embodiment of this invention is described, it is not the meaning which limits this invention.
本発明に係る貼付剤は、支持体と、この支持体上に位置する粘着剤層とを備え、この粘着剤層は、一般式1で示される化合物、その薬理学的に許容される塩又は溶媒和物からなる有効成分と、非イオン性界面活性剤と、水と、を少なくとも含有する。 The patch according to the present invention comprises a support and a pressure-sensitive adhesive layer located on the support, the pressure-sensitive adhesive layer comprising a compound represented by the general formula 1, a pharmacologically acceptable salt thereof, or It contains at least an active ingredient composed of a solvate, a nonionic surfactant, and water.
[粘着剤層]
非イオン性界面活性剤は、従来、水系貼付剤における界面活性剤として使用されてきたが、薬物安定剤として有用であることは想定されなかった。本発明者は、驚くべきことに、非イオン性界面活性剤が水系貼付剤において所定の環状ケトン構造を有する有効成分の反応性(分解性)を抑制することを発見した。具体的に、HLB値が6.0以上9.5以下であり、かつ/又は酸化エチレン付加型であり、酸化エチレン付加モル数が5モル以下である非イオン性界面活性剤は、水系貼付剤において、一般式1に示される化合物が、一般式2又は3で示される化合物へと変化することを抑制する。なお、当該反応は、有効成分のエステル化(特にメントール等とのエステル体の生成)とは全く異なる(詳細は、Journal of Chromatography A、2008年、1208、p.164−174参照)。
[Adhesive layer]
Nonionic surfactants have heretofore been used as surfactants in aqueous patches, but were not expected to be useful as drug stabilizers. The inventor has surprisingly discovered that a nonionic surfactant suppresses the reactivity (degradability) of an active ingredient having a predetermined cyclic ketone structure in an aqueous patch. Specifically, a nonionic surfactant having an HLB value of 6.0 or more and 9.5 or less and / or an ethylene oxide addition type and an ethylene oxide addition mole number of 5 mol or less is an aqueous patch. In the method, the compound represented by the general formula 1 is prevented from changing to the compound represented by the general formula 2 or 3. Note that this reaction is completely different from esterification of an active ingredient (particularly, formation of an ester with menthol or the like) (for details, see Journal of Chromatography A, 2008, 1208, p.164-174).
一般式1から一般式2への変化は、ケトンの炭素と、そのα位の炭素との間の結合が開裂することで生じ、一般式1から一般式3への変化は、α位の炭素がヒドロキシル化されることで生じる。いずれの反応にも、環式構造の炭素数及びRは寄与しないと考えられるため、nは0、1、又は2のいずれかであってよく、Rは任意の有機基であってよい。なお、本発明における有効成分の安定性は、一般式1の化合物から生成される一般式2及び3の化合物の総和が低減することを指し、好ましくは一般式2及び3の化合物の双方の生成量が低減することを指すが、少なくとも一方の生成量が低減すればよい。 The change from General Formula 1 to General Formula 2 occurs when the bond between the ketone carbon and the α-position carbon is cleaved, and the change from General Formula 1 to General Formula 3 is the α-position carbon. Is produced by hydroxylation. In any reaction, since it is considered that the carbon number and R of the cyclic structure do not contribute, n may be 0, 1, or 2, and R may be any organic group. The stability of the active ingredient in the present invention means that the sum of the compounds of the general formulas 2 and 3 produced from the compound of the general formula 1 is reduced. Preferably, both the compounds of the general formulas 2 and 3 are produced. Although the amount is reduced, it is sufficient that at least one of the production amounts is reduced.
従って、一般式1で示される化合物は、特に限定されず、ロキソプロフェン等であってよい。また、薬理学的に許容される塩は、上記化合物及び/又はその溶媒和物の塩であり、特に限定されないが、ナトリウム塩、カリウム塩等のアルカリ金属塩、カルシウム塩、マグネシウム塩等のアルカリ土類金属塩等の1種又は2種以上であってよい。また、溶媒和物は、上記化合物及び/又はその薬理学的に許容される塩の溶媒和物であり、特に限定されないが、一般的には水和物である。なお、有効成分(薬物)は、塩、遊離体、溶媒和物(例えば水和物)、非溶媒和物(例えば非水和物)等の任意の形態で配合されてよい。 Therefore, the compound represented by the general formula 1 is not particularly limited, and may be loxoprofen or the like. The pharmacologically acceptable salt is a salt of the above compound and / or a solvate thereof, and is not particularly limited. However, an alkali metal salt such as a sodium salt or a potassium salt, an alkali salt such as a calcium salt or a magnesium salt is used. It may be one kind or two or more kinds of earth metal salts. The solvate is a solvate of the above compound and / or a pharmacologically acceptable salt thereof, and is not particularly limited, but is generally a hydrate. The active ingredient (drug) may be formulated in any form such as a salt, a free form, a solvate (for example, hydrate), and a non-solvate (for example, non-hydrate).
具体的に、ロキソプロフェンは、次の化学式1に示されるナトリウム塩・二水和物の形態で配合されることが一般的であるが、特に限定されず、他の塩、遊離体、非水和物のいずれの形態で配合されてもよい。
そして、非イオン性界面活性剤は、水系中において、以下の化学式2又は3に示される化合物の生成を抑制する。
HLB値が6.0以上9.5以下である非イオン性界面活性剤は、特に限定されず、ステアリン酸グリセリル(モノグリセリド20%含有。HLB値7.0)、モノステアリン酸ポリグリセリル(HLB値9.0)、トリステアリン酸ポリグリセリル(HLB値9.5)、トリステアリン酸デカグリセリル(HLB値7.5)、トリオレイン酸ポリグリセリル(HLB値7.0)、モノステアリン酸ポリオキシエチレングリセリル(酸化エチレン付加モル数5。HLB値9.5)、ヤシ油脂肪酸ソルビタン(HLB値8.6)、モノパルミチン酸ソルビタン(HLB値6.7)、モノステアリン酸ポリオキシエチレンソルビタン(酸化エチレン付加モル数6。HLB値9.5)、テトラオレイン酸ポリオキシエチレンソルビット(酸化エチレン付加モル数6。HLB値8.5)、ポリオキシエチレン硬化ヒマシ油(酸化エチレン付加モル数5。HLB値6.0)、ポリオキシエチレン硬化ヒマシ油(酸化エチレン付加モル数10。HLB値6.5)、ポリオキシエチレンフィトステロール(酸化エチレン付加モル数5。HLB値9.5)、ポリオキシエチレンラウリルエーテル(酸化エチレン付加モル数2。HLB値9.5)、ポリオキシエチレンステアリルエーテル(酸化エチレン付加モル数2。HLB値8.0)、ポリオキシエチレンラウリルエーテル(酸化エチレン付加モル数4。HLB値9.0)、ポリオキシエチレンオレイルエーテル(酸化エチレン付加モル数2。HLB値7.5)、ポリオキシエチレンベヘニルエーテル(酸化エチレン付加モル数5。HLB値7.0)、ポリオキシエチレンポリオキシプロピレンセチルエーテル(酸化エチレン付加モル数1。酸化プロピレン付加モル数4。HLB値9.5)、ポリオキシエチレンポリオキシプロピレンセチルエーテル(酸化エチレン付加モル数1。酸化プロピレン付加モル数8。HLB値9.5)、モノオレイン酸ポリエチレングリコール(酸化エチレン付加モル数6。HLB値8.5)等の1種又は2種以上であってよい。また、酸化エチレン付加型であり、酸化エチレン付加モル数が5モル以下であるものが好ましく、具体的には、リオキシエチレン硬化ヒマシ油(酸化エチレン付加モル数が5モル)、及びポリオキシエチレンラウリルエーテル(酸化エチレン付加モル数が2モル)の1種又は2種が好ましい。 The nonionic surfactant having an HLB value of 6.0 or more and 9.5 or less is not particularly limited, and glyceryl stearate (containing 20% monoglyceride, HLB value 7.0), polyglyceryl monostearate (HLB value 9) 0.0), polyglyceryl tristearate (HLB value 9.5), decaglyceryl tristearate (HLB value 7.5), polyglyceryl trioleate (HLB value 7.0), polyoxyethylene glyceryl monostearate (oxidized) Ethylene addition mole number 5. HLB value 9.5), palm oil fatty acid sorbitan (HLB value 8.6), sorbitan monopalmitate (HLB value 6.7), monostearate polyoxyethylene sorbitan (ethylene oxide addition mole number) 6. HLB value 9.5), tetraoleic acid polyoxyethylene sorbit (ethylene oxide) Addition mole number 6. HLB value 8.5), polyoxyethylene hydrogenated castor oil (ethylene oxide addition mole number 5. HLB value 6.0), polyoxyethylene hydrogenated castor oil (ethylene oxide addition mole number 10. HLB value 6) .5), polyoxyethylene phytosterol (methylene oxide addition mole number 5. HLB value 9.5), polyoxyethylene lauryl ether (ethylene oxide addition mole number 2. HLB value 9.5), polyoxyethylene stearyl ether (oxidation) Ethylene addition mole number 2. HLB value 8.0), polyoxyethylene lauryl ether (ethylene oxide addition mole number 4. HLB value 9.0), polyoxyethylene oleyl ether (ethylene oxide addition mole number 2. HLB value 7. 5), polyoxyethylene behenyl ether (methylene oxide addition mole number 5. HLB value 7.0) , Polyoxyethylene polyoxypropylene cetyl ether (ethylene oxide addition mole number 1. propylene oxide addition mole number 4. HLB value 9.5), polyoxyethylene polyoxypropylene cetyl ether (ethylene oxide addition mole number 1. propylene oxide addition) Mole number 8. HLB value 9.5), monooleic acid polyethylene glycol (ethylene oxide addition mole number 6, HLB value 8.5), etc. Moreover, it is an ethylene oxide addition type | mold, and the thing whose ethylene oxide addition mole number is 5 mol or less is preferable, Specifically, a reoxyethylene hydrogenated castor oil (ethylene oxide addition mole number is 5 mol), and polyoxyethylene 1 type or 2 types of lauryl ether (2 mol of ethylene oxide addition moles) are preferable.
非イオン性界面活性剤の配合量は、特に限定されないが、有効成分の配合量に対し、10〜500質量%であることが好ましい。非イオン性界面活性剤の配合量は、一般的には、粘着剤層に対し3.0質量%以下の範囲から選ばれてよい。 Although the compounding quantity of a nonionic surfactant is not specifically limited, It is preferable that it is 10-500 mass% with respect to the compounding quantity of an active ingredient. The blending amount of the nonionic surfactant may generally be selected from a range of 3.0% by mass or less with respect to the pressure-sensitive adhesive layer.
非イオン性界面活性剤によって、有効成分の安定性が相当に向上するため、安定性を目的とした他成分の配合量は小さくてよく、又は配合しなくてもよい。具体的に、粘着剤層には、亜硫酸塩、亜硫酸水素塩、及びピロ亜硫酸塩からなる群より選ばれる1種以上を配合してもよいが、その配合量は有効成分の配合量に対し、1質量%以下であってよい。 Since the stability of the active ingredient is considerably improved by the nonionic surfactant, the blending amount of other components for the purpose of stability may be small or may not be blended. Specifically, the pressure-sensitive adhesive layer may contain one or more selected from the group consisting of sulfite, hydrogen sulfite, and pyrosulfite, but the compounding amount is based on the compounding amount of the active ingredient, It may be 1% by mass or less.
亜硫酸塩は、亜硫酸水素のナトリウム塩、カリウム塩等のアルカリ金属塩、カルシウム塩、バリウム塩等のアルカリ土類金属塩等であってよく、亜硫酸水素塩は、ナトリウム塩、カリウム塩等のアルカリ金属塩、アンモニウム塩等であってよく、ピロ亜硫酸塩は、ナトリウム塩、カリウム塩等のアルカリ金属塩等、具体的には亜硫酸ナトリウム、亜硫酸水素ナトリウム、ピロ亜硫酸ナトリウムであってよい。 The sulfite may be an alkali metal salt such as sodium salt or potassium salt of hydrogen sulfite, an alkaline earth metal salt such as calcium salt or barium salt, and the bisulfite is an alkali metal such as sodium salt or potassium salt. It may be a salt, an ammonium salt, or the like, and the pyrosulfite may be an alkali metal salt such as a sodium salt or a potassium salt, specifically sodium sulfite, sodium bisulfite, or sodium pyrosulfite.
本発明に係る含水系貼付剤における粘着剤層は、水を含有する。水の配合量は、特に限定されないが、粘着剤層に対し、30〜70質量%程度であってよい。 The pressure-sensitive adhesive layer in the hydrous patch according to the present invention contains water. Although the compounding quantity of water is not specifically limited, About 30-70 mass% may be sufficient with respect to an adhesive layer.
粘着剤層は、上記成分の他に、必要に応じてポリアクリル酸及び/又はその塩等の賦形剤、界面活性剤、架橋剤、架橋コントロール剤、粘着増強剤、保湿剤、薬物の溶解助剤、pH調節剤、清涼化剤、水溶性高分子化合物、無機粉体、酸化防止剤、防腐剤、色素等の任意成分を含んでよい。 In addition to the above-mentioned components, the pressure-sensitive adhesive layer may be prepared by dissolving excipients such as polyacrylic acid and / or a salt thereof, a surfactant, a cross-linking agent, a cross-linking control agent, an adhesion enhancing agent, a moisturizing agent, and a drug. An optional component such as an auxiliary agent, a pH adjuster, a cooling agent, a water-soluble polymer compound, an inorganic powder, an antioxidant, a preservative, and a pigment may be included.
ポリアクリル酸及び/又はその塩としては、ポリアクリル酸、ポリアクリル酸ナトリウム、ポリアクリル酸部分中和物「NP−800(商品名)」及び「NP−700(商品名)」(昭和電工社製)等が挙げられ、これらは1種単独で又は2種以上を組み合わせて含まれてよい。 Examples of polyacrylic acid and / or salts thereof include polyacrylic acid, sodium polyacrylate, and partially neutralized polyacrylic acid “NP-800 (trade name)” and “NP-700 (trade name)” (Showa Denko) These may be included alone or in combination of two or more.
非イオン性界面活性剤に加え、一般の界面活性剤を配合してもよい。かかる界面活性剤としては、例えば、ジオクチルスルホコハク酸ナトリウム、アルキルサルフェート塩、2−エチルヘキシルアルキル硫酸エステルナトリウム塩、ノルマルドデシルベンゼンスルホン酸ナトリウム等の陰イオン界面活性剤;ヘキサデシルトリメチルアンモニウムクロライド、オクタデシルジメチルベンジルアンモニウムクロライド、ポリオキシエチレンドデシルモノメチルアンモニウムクロライド等の陽イオン界面活性剤が添加されてもよい。 In addition to the nonionic surfactant, a general surfactant may be blended. Examples of such surfactants include anionic surfactants such as sodium dioctyl sulfosuccinate, alkyl sulfate salts, sodium 2-ethylhexyl alkyl sulfate, sodium normal dodecylbenzene sulfonate; hexadecyltrimethylammonium chloride, octadecyldimethylbenzyl Cationic surfactants such as ammonium chloride and polyoxyethylene dodecyl monomethyl ammonium chloride may be added.
架橋剤としては、多価金属塩が挙げられ、その中でもアルミニウム化合物が好ましい。アルミニウム化合物としては、ジヒドロキシアルミニウムアミノアセテート、水酸化アルミニウムのような水酸化物、あるいは塩化アルミニウム、硫酸アルミニウム、酢酸アルミニウム、ステアリン酸アルミニウムのような無機酸又は有機酸の塩、アルミニウム明ばんのような複塩、アルミン酸ナトリウムのようなアルミン酸塩、無機性アルミニウム錯塩及び有機性アルミニウムキレート化合物等が挙げられる。これらのアルミニウム化合物は水溶性であっても、難溶性であってもよい。 Examples of the crosslinking agent include polyvalent metal salts, and among them, aluminum compounds are preferable. Aluminum compounds include hydroxides such as dihydroxyaluminum aminoacetate and aluminum hydroxide, or salts of inorganic or organic acids such as aluminum chloride, aluminum sulfate, aluminum acetate and aluminum stearate, and aluminum alum. Examples thereof include double salts, aluminates such as sodium aluminate, inorganic aluminum complex salts, and organic aluminum chelate compounds. These aluminum compounds may be water-soluble or sparingly soluble.
また、架橋剤として水酸化アルミニウムゲルを用いてもよいが、この場合にはpHが4.5以上6.0以下であることが好ましい。pHが6.0を超えると、水酸化アルミニウムゲルのアルミニウムが溶出しにくく、粘着剤の架橋反応が不充分で保型性が悪化しやすい。これに対し、ジヒドロキシアルミニウムアミノアセテートを用いる場合、粘着剤層のpHは6.0超であってよい。 Moreover, although aluminum hydroxide gel may be used as a crosslinking agent, in this case, the pH is preferably 4.5 or more and 6.0 or less. When the pH exceeds 6.0, aluminum in the aluminum hydroxide gel is difficult to elute, the crosslinking reaction of the pressure-sensitive adhesive is insufficient, and the shape retention tends to deteriorate. On the other hand, when dihydroxyaluminum aminoacetate is used, the pH of the pressure-sensitive adhesive layer may be more than 6.0.
なお、pHはpH調整剤を用いて設定することができ、かかるpH調整剤としては、酒石酸、リン酸、リンゴ酸、クエン酸、塩酸、水酸化ナトリウム、トリエタノールアミン、ジエタノールアミン、ジイソプロパノールアミン等を挙げることができ、これらは1種単独で又は2種以上を組み合わせて含まれてよいが、酒石酸が好ましい。 The pH can be set using a pH adjuster, such as tartaric acid, phosphoric acid, malic acid, citric acid, hydrochloric acid, sodium hydroxide, triethanolamine, diethanolamine, diisopropanolamine, etc. These may be included singly or in combination of two or more, but tartaric acid is preferred.
粘着増強剤としては、メタクリル酸・アクリル酸n−ブチル共重合体、アクリル酸メチル・アクリル酸2−エチルヘキシル共重合体、ポリブテン、エステルガム、テルペン樹脂、脂環族飽和炭化水素樹脂等が挙げられる。その配合量は、粘着剤層に対し1質量%以上30質量%以下であってよく、好ましくは2質量%以上10質量%以下である。 Examples of the adhesion enhancer include methacrylic acid / n-butyl acrylate copolymer, methyl acrylate / 2-ethylhexyl acrylate copolymer, polybutene, ester gum, terpene resin, and alicyclic saturated hydrocarbon resin. . The blending amount thereof may be 1% by mass or more and 30% by mass or less, and preferably 2% by mass or more and 10% by mass or less with respect to the pressure-sensitive adhesive layer.
架橋コントロール剤としては、エデト酸ナトリウム(エチレンジアミン四酢酸二ナトリウム)、クエン酸等が挙げられ、これらは1種単独で又は2種以上を組み合わせて含まれてよいが、エデト酸ナトリウムが好ましい。 Examples of the crosslinking control agent include sodium edetate (disodium ethylenediaminetetraacetate), citric acid, and the like. These may be used alone or in combination of two or more, but sodium edetate is preferred.
保湿剤としては、濃グリセリン、ソルビトール、エチレングリコール、プロピレングリコール、ポリエチレングリコール、ポリプロピレングリコール、流動パラフィン、1,3−プロパンジオール、1,3−ブチレングリコール、マルチトール、キシリトール等の多価アルコール等が挙げられ、これらは1種単独で又は2種以上組み合わせて含まれてよいが、中でも、濃グリセリンが好ましい。なお、グリセリンの配合量は、製造コストやブリーディングの生じやすさ等を考慮して適宜設定されてよい。 Examples of humectants include concentrated glycerin, sorbitol, ethylene glycol, propylene glycol, polyethylene glycol, polypropylene glycol, liquid paraffin, 1,3-propanediol, 1,3-butylene glycol, polyhydric alcohols such as maltitol and xylitol. These may be included singly or in combination of two or more, and among them, concentrated glycerin is preferable. In addition, the blending amount of glycerin may be appropriately set in consideration of the manufacturing cost, the ease of occurrence of bleeding, and the like.
薬物の溶解助剤としては、クロタミトン、N−メチル−2−ピロリドン等のピロリドン誘導体、ハッカ油、1,3−ブチレングリコール等が挙げられ、これらは1種単独で又は2種以上組み合わせて含まれてよい。 Drug dissolution aids include crotamiton, pyrrolidone derivatives such as N-methyl-2-pyrrolidone, mint oil, 1,3-butylene glycol, etc., and these are included alone or in combination of two or more. It's okay.
清涼化剤としては、カンフル、チモールの他、l−メントール、dl−メントール、2−メチル−3−(l−メンチルオキシ)プロパン−1,2−ジオール、3−l−メントキシプロパン−1,2−ジオール、5−メチル−2−(l−メチルエチル)−シクロヘキシル−2−ヒドロキシプロピオネート等のメントール誘導体等が挙げられ、これらは1種単独で又は2種以上組み合わせて含まれてよい。 As a refreshing agent, in addition to camphor and thymol, l-menthol, dl-menthol, 2-methyl-3- (l-menthyloxy) propane-1,2-diol, 3-l-mentoxypropane-1, Examples include menthol derivatives such as 2-diol and 5-methyl-2- (l-methylethyl) -cyclohexyl-2-hydroxypropionate, and these may be included singly or in combination of two or more. .
水溶性高分子化合物としては、ゼラチン、カンテン、ポリビニルアルコール、ポリビニルピロリドン、プロピレンカーボネート、カルボキシメチルセルロース、カルメロースナトリウム、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース、ヒドロキシエチルセルロース、メチルセルロース、アルギン酸ナトリウム、無水マレイン酸共重合体、カラギーナン等が挙げられ、これらは1種単独で又は2種以上組み合わせて含まれてよい。 Water-soluble polymer compounds include gelatin, agar, polyvinyl alcohol, polyvinyl pyrrolidone, propylene carbonate, carboxymethylcellulose, carmellose sodium, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, methylcellulose, sodium alginate, maleic anhydride copolymer , Carrageenan and the like, and these may be included singly or in combination of two or more.
無機粉体としては、例えばカオリン、酸化亜鉛、酸化チタン、無水ケイ酸等が挙げられ、これらは1種単独で又は2種以上組み合わせて含まれてよい。 Examples of the inorganic powder include kaolin, zinc oxide, titanium oxide, and silicic anhydride, and these may be used alone or in combination of two or more.
酸化防止剤としては、酢酸トコフェロール、アスコルビン酸及び/又はその誘導体、亜硫酸ナトリウム、ジブチルヒドロキシトルエン等が挙げられ、これらは1種単独で又は2種以上組み合わせて含まれてよい。 Examples of the antioxidant include tocopherol acetate, ascorbic acid and / or a derivative thereof, sodium sulfite, dibutylhydroxytoluene and the like, and these may be used alone or in combination of two or more.
防腐剤としては、メチルパラベン、ブチルバラベン、プロピルパラベン、チモール等が挙げられ、これらは1種単独で又は2種以上組み合わせて含まれてよい。 Examples of the preservative include methylparaben, butylbaraben, propylparaben, thymol, and the like, and these may be included singly or in combination of two or more.
色素としては、その種類は特に限定されず、法定色素ハンドブック記載の色素が挙げられ、これらは1種単独で又は2種以上組み合わせて使用することができる。 The type of the dye is not particularly limited, and examples thereof include dyes described in the Legal Dye Handbook, and these can be used alone or in combination of two or more.
[支持体]
支持体は、従来から知られている貼付剤に用いられる織布、不織布、編布等の布帛、樹脂フィルム、紙及び、それらの積層体で構成されてよい。支持体の材質は、ポリプロピレン、ポリエチレン、ポリブチレン、ポリエチレンテレフタレート、レイヨン、綿、ポリウレタンからなる群から選ばれる1種又は2種以上であってよく、特に限定されないが、ポリエチレンテレフタレートであることが好ましい。コストの面からは、ポリエチレンテレフタレートからなる不織布で構成された支持体が好ましく用いられる。また、樹脂フィルムを用いる場合には、白色、肌色等の塗料を印刷し又は練り込んで着色を施したり、文字等を記入したりした支持体を用いてもよく、粘着剤の投錨性を向上するために、ポリウレタン処理や、艶消し処理等を施した支持体を使用することもできる。
[Support]
The support may be composed of a fabric such as a woven fabric, a non-woven fabric, and a knitted fabric used for conventionally known patches, a resin film, paper, and a laminate thereof. The material of the support may be one or more selected from the group consisting of polypropylene, polyethylene, polybutylene, polyethylene terephthalate, rayon, cotton, and polyurethane, and is not particularly limited, but is preferably polyethylene terephthalate. From the viewpoint of cost, a support composed of a nonwoven fabric made of polyethylene terephthalate is preferably used. In addition, when using a resin film, it is possible to use a support that has been printed or kneaded with white, skin color, or colored or filled with characters, etc., improving the anchoring property of the adhesive. In order to achieve this, it is also possible to use a support that has been subjected to polyurethane treatment, matting treatment, or the like.
[剥離ライナ]
本発明に係る貼付剤は、粘着剤層を被覆する剥離ライナを更に備えてもよい。かかる剥離ライナとしては、ポリエチレンテレフタレート、ポリプロリピレン等の樹脂フィルムが好ましく、シリコン等の剥離処理をしたもの、エンボス加工を施したものを用いてもよい。また、白色等の塗料を印刷し又は練り込んだものを剥離ライナとして用いることもできる。
[Peeling liner]
The patch according to the present invention may further include a release liner that covers the pressure-sensitive adhesive layer. As such a release liner, a resin film such as polyethylene terephthalate or polypropylene is preferable, and a release film such as silicon or an embossed film may be used. Moreover, what printed or kneaded paints, such as white, can also be used as a peeling liner.
(調製方法)
本発明の貼付剤は、従来の方法で調製することができ、上記必須成分及び必要に応じて上記任意成分を適宜配合して公知の方法で均一になるまで練合し、貼付剤単位面積当りにおける粘着剤質量が0.03〜0.15g/cm2になるように剥離ライナに展延した後、その粘着剤層の表面に更に支持体を積層し、次いで100mm×140mmの矩形状に裁断して調製することができる。また、支持体上に先に粘着剤を展延した後、剥離ライナをその上に積層することによって調製することもできる。
(Preparation method)
The patch of the present invention can be prepared by a conventional method, and the above-mentioned essential components and, if necessary, the above optional components are appropriately blended and kneaded until uniform by a known method. After spreading on the release liner so that the pressure-sensitive adhesive mass is 0.03 to 0.15 g / cm 2 , a support is further laminated on the surface of the pressure-sensitive adhesive layer, and then cut into a 100 mm × 140 mm rectangular shape Can be prepared. It can also be prepared by first spreading a pressure-sensitive adhesive on a support and then laminating a release liner thereon.
以下、実施例及び比較例を示し、本発明を具体的に説明するが、本発明が実施例に限定されるものではない。 EXAMPLES Hereinafter, although an Example and a comparative example are shown and this invention is demonstrated concretely, this invention is not limited to an Example.
[試験例1]
表1に示す各成分を一定時間に亘って撹拌し混合した後、剥離ライナ上に、貼付剤1枚当り(140mm×100mm)の粘着剤質量が約10gになるように均一に展延した。その後、粘着剤層の表面にポリエチレンテレフタレート製不織布を貼り合わせることで、貼付剤を調製した。
[Test Example 1]
Each component shown in Table 1 was stirred and mixed for a certain period of time, and then uniformly spread on the release liner so that the adhesive mass per patch (140 mm × 100 mm) was about 10 g. Then, the patch was prepared by bonding together the nonwoven fabric made from a polyethylene terephthalate on the surface of an adhesive layer.
表1における界面活性剤を表2に示すものとし、貼付剤を調製した。各貼付剤を40℃又は60℃で放置した後、表面積10cm2の断片を切り取り、、その質量を精密に量った。その後、剥離ライナフィルムを剥がし、50mLの遠沈管に入れ、そこにメタノールを添加し、30分間振盪して薬物を抽出した。抽出液を高速遠心分離し、ろ過処理した液を試料溶液として、HPLCにて、化学式1〜3、ロキソプロフェンのグリセロールエステル(「GE」という)、メントールエステル(「ME」という)の質量を測定した。この結果を表3に示す。 Table 1 shows the surfactants in Table 1, and prepared patches. Each patch was allowed to stand at 40 ° C. or 60 ° C., and then a piece having a surface area of 10 cm 2 was cut out and its mass was accurately measured. Thereafter, the release liner film was peeled off, placed in a 50 mL centrifuge tube, methanol was added thereto, and the drug was extracted by shaking for 30 minutes. The extract was centrifuged at high speed, and the mass of the glycerol ester (referred to as “GE”) and menthol ester (referred to as “ME”) of chemical formulas 1 to 3, loxoprofen was measured by HPLC using the filtered solution as a sample solution. . The results are shown in Table 3.
表2及び3に示されるように、全実施例で特に化学式3の生成が抑制され、中でも実施例8〜13では、化学式2及び3の双方の生成が更に抑制された。これにより、非イオン性界面活性剤が水系における化学式3の生成を抑制し、6.0以上9.5以下のHLB値を有する酸化エチレン付加型であり、酸化エチレン付加モル数が5モル以下である非界面活性剤は、化学式2及び3の双方の生成を更に抑制することが分かった。一方、ロキソプロフェンのエステル体の生成量は各貼付剤間で有意な差は確認できなかった。これにより、非イオン性界面活性剤は、水系での化学式1から化学式2及び3への変化を特異的に抑制することが分かった。 As shown in Tables 2 and 3, the generation of Chemical Formula 3 was particularly suppressed in all Examples, and in particular, in Examples 8 to 13, the generation of both Chemical Formulas 2 and 3 was further suppressed. As a result, the nonionic surfactant is an ethylene oxide addition type having an HLB value of 6.0 or more and 9.5 or less, which suppresses the formation of Chemical Formula 3 in the aqueous system, and the number of moles of ethylene oxide addition is 5 mol or less. Certain non-surfactants have been found to further inhibit the formation of both Formulas 2 and 3. On the other hand, the amount of loxoprofen ester produced was not significantly different between the patches. Thereby, it turned out that a nonionic surfactant suppresses specifically the change from Chemical formula 1 to Chemical formula 2 and 3 in an aqueous system.
実施例8及び市販品(ロキソニン(登録商標)パップ100mg:界面活性剤としてポリソルベート80を配合)の貼付剤を40℃及び60℃で1〜6ヶ月間に亘り放置し、粘着剤層(薬剤面)が貼付剤の作製直後からどの程度着色したのかを色差(ΔE)で評価した。その結果を表4に示す。色差(ΔE)は、粘着剤層表面の色度を色彩色差計(X−Rite Inc.製、Model SP64)により測定し、貼付剤作製直後と、40℃及び60℃にて1〜6ヶ月間放置後との間での色度の差を、下記の式で算出することにより得た。つまり、白−黒の程度をL−スケール、赤−緑の程度をa−スケール、青−黄の程度b−スケールでそれぞれ表す場合、色差は、各スケールの差の二乗和の平方根、ΔE(=((Δa)2+(Δb)2+(ΔL)2)1/2)で表される。 The patch of Example 8 and a commercially available product (Loxonin (registered trademark) Pap 100 mg: compounded with polysorbate 80 as a surfactant) was allowed to stand at 40 ° C. and 60 ° C. for 1 to 6 months, and an adhesive layer (drug surface) ) Was evaluated by the color difference (ΔE) to determine how much color was immediately after the preparation of the patch. The results are shown in Table 4. The color difference (ΔE) is determined by measuring the chromaticity of the surface of the pressure-sensitive adhesive layer with a color difference meter (Model SP64, manufactured by X-Rite Inc.) and immediately after preparation of the patch, at 40 ° C. and 60 ° C. for 1 to 6 months. The difference in chromaticity after being allowed to stand was obtained by calculating with the following formula. That is, when the white-black degree is represented by the L-scale, the red-green degree is represented by the a-scale, and the blue-yellow degree b-scale, respectively, the color difference is the square root of the square sum of the differences between the scales, ΔE ( = ((Δa) 2 + (Δb) 2 + (ΔL) 2 ) 1/2 ).
表4に示されるように、時間の経過に伴う粘着剤層の着色が、市販品よりも実施例8において抑制されることが確認された。 As shown in Table 4, it was confirmed that coloring of the pressure-sensitive adhesive layer with the passage of time was suppressed in Example 8 in comparison with the commercially available product.
Claims (1)
前記粘着剤層は、ロキソプロフェン、その薬理学的に許容される塩又は溶媒和物からなる有効成分と、非イオン性界面活性剤と、水と、を含有し、
前記非イオン性界面活性剤は、HLB値が6.0以上9.5以下であり、ポリオキシエチレン硬化ヒマシ油(酸化エチレン付加モル数が5モル)、及びポリオキシエチレンラウリルエーテル(酸化エチレン付加モル数が2モル)からなる群より選ばれる1種以上である、含水系貼付剤。
A hydrous patch comprising a support and an adhesive layer located on the support,
The pressure-sensitive adhesive layer contains loxoprofen, an active ingredient composed of a pharmacologically acceptable salt or solvate thereof, a nonionic surfactant, and water.
The nonionic surfactant has an HLB value of 6.0 to 9.5, polyoxyethylene hydrogenated castor oil (5 moles of ethylene oxide added), and polyoxyethylene lauryl ether (ethylene oxide added). A hydrous patch which is at least one selected from the group consisting of 2 moles).
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BR112017013255B1 (en) | 2014-12-22 | 2022-08-09 | Hisamitsu Pharmaceutical Co., Inc | POULTICE |
WO2016136556A1 (en) * | 2015-02-24 | 2016-09-01 | 久光製薬株式会社 | Adhesive skin poultice |
JP6613878B2 (en) * | 2015-12-25 | 2019-12-04 | ライオン株式会社 | Oral polymer gel formulation |
JP6594937B2 (en) * | 2016-09-05 | 2019-10-23 | 久光製薬株式会社 | Sheet-like pack and method for producing the same |
KR102000435B1 (en) * | 2018-01-18 | 2019-07-16 | 대화제약 주식회사 | A pharmaceutical composition for transdermal administration in the form of hydrogel patch |
JP2019206497A (en) * | 2018-05-30 | 2019-12-05 | 小林製薬株式会社 | External pharmaceutical composition |
KR20210065931A (en) * | 2018-09-26 | 2021-06-04 | 니찌방 가부시기가이샤 | functional patch |
EP3925604A4 (en) | 2019-02-14 | 2022-11-16 | Hisamitsu Pharmaceutical Co., Inc. | Poultice |
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JP3466305B2 (en) * | 1994-12-12 | 2003-11-10 | 久光製薬株式会社 | Dissolving agent and external preparation containing the dissolving agent |
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