JPH0959152A - Isosorbide dinitrate-containing plaster - Google Patents
Isosorbide dinitrate-containing plasterInfo
- Publication number
- JPH0959152A JPH0959152A JP21052095A JP21052095A JPH0959152A JP H0959152 A JPH0959152 A JP H0959152A JP 21052095 A JP21052095 A JP 21052095A JP 21052095 A JP21052095 A JP 21052095A JP H0959152 A JPH0959152 A JP H0959152A
- Authority
- JP
- Japan
- Prior art keywords
- adhesive
- patch
- component
- pressure
- polyvinyl acetate
- 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.)
- Pending
Links
- MOYKHGMNXAOIAT-JGWLITMVSA-N isosorbide dinitrate Chemical compound [O-][N+](=O)O[C@H]1CO[C@@H]2[C@H](O[N+](=O)[O-])CO[C@@H]21 MOYKHGMNXAOIAT-JGWLITMVSA-N 0.000 title claims description 62
- 229960000201 isosorbide dinitrate Drugs 0.000 title claims description 32
- 239000011505 plaster Substances 0.000 title abstract 3
- 239000000203 mixture Substances 0.000 claims abstract description 36
- 229920001296 polysiloxane Polymers 0.000 claims abstract description 27
- 239000004744 fabric Substances 0.000 claims abstract description 25
- 238000005243 fluidization Methods 0.000 claims abstract description 17
- 230000003405 preventing effect Effects 0.000 claims abstract description 12
- 239000012790 adhesive layer Substances 0.000 claims abstract description 11
- 229920006267 polyester film Polymers 0.000 claims abstract description 9
- 229920000728 polyester Polymers 0.000 claims abstract description 6
- 230000001070 adhesive effect Effects 0.000 claims description 101
- 239000000853 adhesive Substances 0.000 claims description 99
- 239000004820 Pressure-sensitive adhesive Substances 0.000 claims description 70
- 229920002689 polyvinyl acetate Polymers 0.000 claims description 43
- 239000011118 polyvinyl acetate Substances 0.000 claims description 43
- 239000010410 layer Substances 0.000 claims description 26
- 239000013464 silicone adhesive Substances 0.000 claims description 21
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 claims description 18
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 claims description 17
- -1 2-ethylhexyl Chemical group 0.000 claims description 15
- 229920001577 copolymer Polymers 0.000 claims description 13
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 claims description 11
- 229910052751 metal Inorganic materials 0.000 claims description 10
- 239000002184 metal Substances 0.000 claims description 10
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 10
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 10
- 238000007334 copolymerization reaction Methods 0.000 claims description 9
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 7
- 150000001875 compounds Chemical class 0.000 claims description 5
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 claims description 5
- 239000004793 Polystyrene Substances 0.000 claims description 4
- 229940087168 alpha tocopherol Drugs 0.000 claims description 4
- 239000013522 chelant Substances 0.000 claims description 4
- 229960000984 tocofersolan Drugs 0.000 claims description 4
- 235000004835 α-tocopherol Nutrition 0.000 claims description 4
- 239000002076 α-tocopherol Substances 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 125000002524 organometallic group Chemical group 0.000 claims description 3
- 229920002223 polystyrene Polymers 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 2
- 229920006395 saturated elastomer Polymers 0.000 claims description 2
- 235000003441 saturated fatty acids Nutrition 0.000 claims description 2
- 150000004671 saturated fatty acids Chemical class 0.000 claims description 2
- 235000021122 unsaturated fatty acids Nutrition 0.000 claims description 2
- 150000004670 unsaturated fatty acids Chemical class 0.000 claims description 2
- YWXYYJSYQOXTPL-JGWLITMVSA-N [(3r,3ar,6s,6as)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl] nitrate Chemical compound [O-][N+](=O)O[C@H]1CO[C@@H]2[C@H](O)CO[C@@H]21 YWXYYJSYQOXTPL-JGWLITMVSA-N 0.000 claims 5
- 150000002739 metals Chemical class 0.000 claims 1
- 238000010521 absorption reaction Methods 0.000 abstract description 5
- 208000010201 Exanthema Diseases 0.000 abstract description 4
- 201000005884 exanthem Diseases 0.000 abstract description 4
- 206010037844 rash Diseases 0.000 abstract description 4
- 231100000046 skin rash Toxicity 0.000 abstract description 4
- 238000013268 sustained release Methods 0.000 abstract description 3
- 239000012730 sustained-release form Substances 0.000 abstract description 3
- 239000003795 chemical substances by application Substances 0.000 abstract 2
- KLDXJTOLSGUMSJ-JGWLITMVSA-N Isosorbide Chemical compound O[C@@H]1CO[C@@H]2[C@@H](O)CO[C@@H]21 KLDXJTOLSGUMSJ-JGWLITMVSA-N 0.000 abstract 1
- 229960002479 isosorbide Drugs 0.000 abstract 1
- 238000010030 laminating Methods 0.000 abstract 1
- 229920002554 vinyl polymer Polymers 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 13
- 238000002360 preparation method Methods 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 206010040880 Skin irritation Diseases 0.000 description 9
- 229940079593 drug Drugs 0.000 description 9
- 239000003814 drug Substances 0.000 description 9
- 238000000034 method Methods 0.000 description 9
- 238000002156 mixing Methods 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 230000036556 skin irritation Effects 0.000 description 9
- 231100000475 skin irritation Toxicity 0.000 description 9
- 239000000243 solution Substances 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 229920001971 elastomer Polymers 0.000 description 6
- GOXQRTZXKQZDDN-UHFFFAOYSA-N 2-Ethylhexyl acrylate Chemical compound CCCCC(CC)COC(=O)C=C GOXQRTZXKQZDDN-UHFFFAOYSA-N 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 238000007796 conventional method Methods 0.000 description 5
- 229920000139 polyethylene terephthalate Polymers 0.000 description 5
- 239000005020 polyethylene terephthalate Substances 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 125000005907 alkyl ester group Chemical group 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- WOZVHXUHUFLZGK-UHFFFAOYSA-N dimethyl terephthalate Chemical compound COC(=O)C1=CC=C(C(=O)OC)C=C1 WOZVHXUHUFLZGK-UHFFFAOYSA-N 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 239000013557 residual solvent Substances 0.000 description 4
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-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
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- QYKIQEUNHZKYBP-UHFFFAOYSA-N Vinyl ether Chemical class C=COC=C QYKIQEUNHZKYBP-UHFFFAOYSA-N 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- 238000009792 diffusion process Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000003623 enhancer Substances 0.000 description 3
- 239000005038 ethylene vinyl acetate Substances 0.000 description 3
- 239000012510 hollow fiber Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000004745 nonwoven fabric Substances 0.000 description 3
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- AOBORMOPSGHCAX-DGHZZKTQSA-N tocofersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-DGHZZKTQSA-N 0.000 description 3
- 239000002759 woven fabric Substances 0.000 description 3
- UZKWTJUDCOPSNM-UHFFFAOYSA-N 1-ethenoxybutane Chemical compound CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 2
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- MSCCTZZBYHQMQJ-AZAGJHQNSA-N Tocopheryl nicotinate Chemical compound C([C@@](OC1=C(C)C=2C)(C)CCC[C@H](C)CCC[C@H](C)CCCC(C)C)CC1=C(C)C=2OC(=O)C1=CC=CN=C1 MSCCTZZBYHQMQJ-AZAGJHQNSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 239000003522 acrylic cement Substances 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- POJWUDADGALRAB-UHFFFAOYSA-N allantoin Chemical compound NC(=O)NC1NC(=O)NC1=O POJWUDADGALRAB-UHFFFAOYSA-N 0.000 description 2
- ADCOVFLJGNWWNZ-UHFFFAOYSA-N antimony trioxide Chemical compound O=[Sb]O[Sb]=O ADCOVFLJGNWWNZ-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- KVYGGMBOZFWZBQ-UHFFFAOYSA-N benzyl nicotinate Chemical compound C=1C=CN=CC=1C(=O)OCC1=CC=CC=C1 KVYGGMBOZFWZBQ-UHFFFAOYSA-N 0.000 description 2
- VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical compound [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 description 2
- 239000001639 calcium acetate Substances 0.000 description 2
- 229960005147 calcium acetate Drugs 0.000 description 2
- 235000011092 calcium acetate Nutrition 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 239000002131 composite material Substances 0.000 description 2
- LZCLXQDLBQLTDK-UHFFFAOYSA-N ethyl 2-hydroxypropanoate Chemical compound CCOC(=O)C(C)O LZCLXQDLBQLTDK-UHFFFAOYSA-N 0.000 description 2
- MMXKVMNBHPAILY-UHFFFAOYSA-N ethyl laurate Chemical compound CCCCCCCCCCCC(=O)OCC MMXKVMNBHPAILY-UHFFFAOYSA-N 0.000 description 2
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 2
- 229940093471 ethyl oleate Drugs 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- YNBADRVTZLEFNH-UHFFFAOYSA-N methyl nicotinate Chemical compound COC(=O)C1=CC=CN=C1 YNBADRVTZLEFNH-UHFFFAOYSA-N 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 238000006068 polycondensation reaction Methods 0.000 description 2
- 238000006116 polymerization reaction Methods 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 229940042585 tocopherol acetate Drugs 0.000 description 2
- 229950009883 tocopheryl nicotinate Drugs 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 1
- YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-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
- POILWHVDKZOXJZ-ARJAWSKDSA-M (z)-4-oxopent-2-en-2-olate Chemical compound C\C([O-])=C\C(C)=O POILWHVDKZOXJZ-ARJAWSKDSA-M 0.000 description 1
- LYCAIKOWRPUZTN-NMQOAUCRSA-N 1,2-dideuteriooxyethane Chemical compound [2H]OCCO[2H] LYCAIKOWRPUZTN-NMQOAUCRSA-N 0.000 description 1
- AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical compound CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-UHFFFAOYSA-N 0.000 description 1
- NJPQAIBZIHNJDO-UHFFFAOYSA-N 1-dodecylpyrrolidin-2-one Chemical compound CCCCCCCCCCCCN1CCCC1=O NJPQAIBZIHNJDO-UHFFFAOYSA-N 0.000 description 1
- BDKLKNJTMLIAFE-UHFFFAOYSA-N 2-(3-fluorophenyl)-1,3-oxazole-4-carbaldehyde Chemical compound FC1=CC=CC(C=2OC=C(C=O)N=2)=C1 BDKLKNJTMLIAFE-UHFFFAOYSA-N 0.000 description 1
- TWJNQYPJQDRXPH-UHFFFAOYSA-N 2-cyanobenzohydrazide Chemical compound NNC(=O)C1=CC=CC=C1C#N TWJNQYPJQDRXPH-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- HBTAOSGHCXUEKI-UHFFFAOYSA-N 4-chloro-n,n-dimethyl-3-nitrobenzenesulfonamide Chemical compound CN(C)S(=O)(=O)C1=CC=C(Cl)C([N+]([O-])=O)=C1 HBTAOSGHCXUEKI-UHFFFAOYSA-N 0.000 description 1
- FXTXRXXCMFFRTL-UHFFFAOYSA-N 4-ethyl-2-methylideneoctanoic acid Chemical compound CCCCC(CC)CC(=C)C(O)=O FXTXRXXCMFFRTL-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
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- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
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- 241001465754 Metazoa Species 0.000 description 1
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- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
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- ODHCTXKNWHHXJC-GSVOUGTGSA-N Pyroglutamic acid Natural products OC(=O)[C@H]1CCC(=O)N1 ODHCTXKNWHHXJC-GSVOUGTGSA-N 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 239000003655 absorption accelerator Substances 0.000 description 1
- 229940124532 absorption promoter Drugs 0.000 description 1
- ODHCTXKNWHHXJC-UHFFFAOYSA-N acide pyroglutamique Natural products OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 229960000458 allantoin Drugs 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 235000010210 aluminium Nutrition 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- 229950004580 benzyl nicotinate Drugs 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229960000846 camphor Drugs 0.000 description 1
- 229930008380 camphor Natural products 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 229960001777 castor oil Drugs 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229940031578 diisopropyl adipate Drugs 0.000 description 1
- 239000004205 dimethyl polysiloxane Substances 0.000 description 1
- 235000013870 dimethyl polysiloxane Nutrition 0.000 description 1
- 238000007598 dipping method Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 229960000878 docusate sodium Drugs 0.000 description 1
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 1
- GVGUFUZHNYFZLC-UHFFFAOYSA-N dodecyl benzenesulfonate;sodium Chemical compound [Na].CCCCCCCCCCCCOS(=O)(=O)C1=CC=CC=C1 GVGUFUZHNYFZLC-UHFFFAOYSA-N 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 229940116333 ethyl lactate Drugs 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 229940014259 gelatin Drugs 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000009477 glass transition Effects 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229920001519 homopolymer Polymers 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229960000448 lactic acid Drugs 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- UEGPKNKPLBYCNK-UHFFFAOYSA-L magnesium acetate Chemical compound [Mg+2].CC([O-])=O.CC([O-])=O UEGPKNKPLBYCNK-UHFFFAOYSA-L 0.000 description 1
- 239000011654 magnesium acetate Substances 0.000 description 1
- 235000011285 magnesium acetate Nutrition 0.000 description 1
- 229940069446 magnesium acetate Drugs 0.000 description 1
- 229940082328 manganese acetate tetrahydrate Drugs 0.000 description 1
- CESXSDZNZGSWSP-UHFFFAOYSA-L manganese(2+);diacetate;tetrahydrate Chemical compound O.O.O.O.[Mn+2].CC([O-])=O.CC([O-])=O CESXSDZNZGSWSP-UHFFFAOYSA-L 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- RROAXNYROFIJOE-UHFFFAOYSA-N methoxycarbonyl benzenesulfonate Chemical compound COC(=O)OS(=O)(=O)C1=CC=CC=C1 RROAXNYROFIJOE-UHFFFAOYSA-N 0.000 description 1
- 229960001238 methylnicotinate Drugs 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000098 polyolefin Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 150000004040 pyrrolidinones Chemical class 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 229920002050 silicone resin Polymers 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 229940083542 sodium Drugs 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229940087562 sodium acetate trihydrate Drugs 0.000 description 1
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 1
- 229940080264 sodium dodecylbenzenesulfonate Drugs 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 229940031439 squalene Drugs 0.000 description 1
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000005809 transesterification reaction Methods 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は硝酸イソソルビド含
有貼付剤に関する。更に詳しくは、硝酸イソソルビド
（以下、ＩＳＤＮと略記することもある）を他の特定の
成分と特定比率で混合させた粘着性組成物が柔軟な担持
体の上に形成された、徐放性に優れ、かつ良好な経皮吸
収性を有する貼付剤に関する。TECHNICAL FIELD The present invention relates to a patch containing isosorbide dinitrate. More specifically, an adhesive composition obtained by mixing isosorbide dinitrate (hereinafter sometimes abbreviated as ISDN) with other specific components in a specific ratio is formed on a flexible carrier to give sustained release. The present invention relates to a patch having excellent transdermal absorbability.
【０００２】[0002]
【従来の技術】硝酸イソソルビド等の薬剤が経皮吸収さ
れることは公知であり、これら薬剤を含有する貼付剤と
して、既に多数の商品が開発されている。その貼付剤に
使用する粘着剤として特定範囲のガラス転移温度を有す
るアクリル系、シリコーン系、ゴム系等の粘着剤が好ま
しいことは、例えば、特開昭５７−１１６０１１号公報
等に示されている。また、日本薬学会第５年会（平成元
年９月２６〜２８日）において、小国らはＩＳＤＮを含
有する貼付剤についてアクリル系、シリコーン系、ゴム
系の粘着剤を比較し、この三者は経皮吸収性がほぼ同じ
であったと報告している。前述の特開昭５７−１１６０
１１号公報では、各種の粘着剤の中から特にアクリル系
粘着剤が好ましいとしてその後補正を行って公告（特公
平４−７４３２９号）されている。2. Description of the Related Art It is known that drugs such as isosorbide dinitrate are percutaneously absorbed, and a number of products have already been developed as patches containing these drugs. It is shown in, for example, JP-A No. 57-116011 that the pressure-sensitive adhesive used in the patch is preferably an acrylic-based, silicone-based or rubber-based pressure-sensitive adhesive having a glass transition temperature in a specific range. . Also, at the 5th Annual Meeting of the Pharmaceutical Society of Japan (September 26-28, 1989), Oguni et al. Compared acrylic, silicone, and rubber adhesives for ISDN-containing patches and Reported that the transdermal absorbability was about the same. The above-mentioned JP-A-57-1160
In Japanese Patent Laid-Open No. 11-43, an acrylic pressure-sensitive adhesive is particularly preferable among various pressure-sensitive adhesives, and a public notice is made after making corrections (Japanese Patent Publication No. 4-74329).
【０００３】すなわち、従来、ＩＳＤＮを含有する貼付
剤において、ＩＳＤＮの経皮吸収性と粘着剤との関係か
らは、アクリル系粘着剤が好ましいとされるか、あるい
は前記アクリル系、シリコーン系、ゴム系の粘着剤は同
等であると考えられていた。また、特開平６−３４５４
０号公報では、シリコーン系粘着剤（Ａ）と、ポリ酢酸
ビニル系粘着剤（Ｂ）からなり、それらの重量比率
（Ａ：Ｂ）が８５：１５〜６０：４０の混合系粘着剤で
あり、（Ａ＋Ｂ）に対するＩＳＤＮ（Ｃ）の重量比率が
９０：１０〜６０：４０である硝酸イソソルビド含有貼
付剤が、アクリル系粘着剤又はシリコーン系粘着剤単独
系よりも顕著に経皮吸収性を改善することが記載されて
いる。That is, in the past, in the patch containing ISDN, an acrylic adhesive was preferred from the viewpoint of the transdermal absorbability of ISDN and the adhesive, or the above-mentioned acrylic, silicone or rubber. The adhesives of the system were considered equivalent. In addition, JP-A-6-3454
No. 0 is a mixed adhesive composed of a silicone-based adhesive (A) and a polyvinyl acetate-based adhesive (B), and their weight ratio (A: B) is 85:15 to 60:40. , An isosorbide dinitrate-containing patch in which the weight ratio of ISDN (C) to (A + B) is 90:10 to 60:40 significantly improves the transdermal absorbability as compared to the acrylic adhesive or the silicone adhesive alone. It is described to do.
【０００４】ところで、貼付剤の欠点の一つは皮膚かぶ
れの発生であり、この皮膚かぶれの発生を少なくする方
法として種々の提案がなされている。その一つは製剤サ
イズを小さくすることによって皮膚かぶれが発生する部
分を少なくすることであるが、このためには単位面積当
たりの経皮吸収性を高めることが必要となる。そこで経
皮吸収性を高めるために各種の吸収促進剤が提案されて
いるが、吸収促進剤は一般に低分子量であることも関係
して皮膚刺激性が認められるものが多い。また吸収促進
剤を多量に添加すると、得られる粘着性組成物の粘着力
が低下する等の問題もあり、皮膚かぶれの発生を少なく
しかつ経皮吸収性ないし粘着力にも優れた貼付剤を提供
することに必ずしも成功しているとはいえない。一方、
可塑化作用成分は粘着剤の粘着力を調整する作用を有し
ており、粘着性組成物に併用するのが好ましいが、かか
る可塑化作用成分を多量に添加すると得られる粘着性組
成物の粘着力が低下する。さらに、貼付中に粘着剤が流
動化する結果、貼付剤の周辺部に粘着剤がにじみ出し、
衣類や外部から汚れを付着させて黒ずみを生ずるという
問題を生じる。By the way, one of the drawbacks of patches is the occurrence of skin irritation, and various proposals have been made as methods for reducing the occurrence of skin irritation. One of them is to reduce the area where skin irritation occurs by reducing the size of the preparation. For this purpose, it is necessary to enhance the transdermal absorbability per unit area. Therefore, various absorption enhancers have been proposed in order to enhance the transdermal absorbability. However, many of the absorption enhancers are generally found to have skin irritation due to their low molecular weight. In addition, when a large amount of an absorption accelerator is added, there is a problem that the adhesive strength of the obtained adhesive composition is lowered, etc., and a patch that reduces the occurrence of skin irritation and is superior in transdermal absorbability or adhesive strength It is not always successful in providing. on the other hand,
The plasticizing component has an action of adjusting the adhesive strength of the pressure-sensitive adhesive and is preferably used in combination with the pressure-sensitive adhesive composition, but the tackiness of the pressure-sensitive adhesive composition obtained by adding a large amount of the plasticizing component. The power decreases. Furthermore, as a result of the fluidization of the adhesive during application, the adhesive oozes out around the adhesive,
This causes a problem that stains are attached from clothes or the outside to cause darkening.
【０００５】[0005]
【発明が解決しようとする課題】本発明は、粘着力が適
度であり、皮膚刺激が少なく、しかも製剤からの粘着剤
のにじみ出しの少ない経皮吸収性の良好な徐放性の硝酸
イソソルビド含有貼付剤を提供することを目的とする。
本発明者らはこのような課題を解決するため鋭意研究の
結果、本発明に到達したものである。DISCLOSURE OF THE INVENTION The present invention contains a sustained-release isosorbide dinitrate having a suitable adhesive force, less skin irritation, and less permeation of the pressure-sensitive adhesive from the preparation and good transdermal absorbability. The purpose is to provide a patch.
The present inventors have arrived at the present invention as a result of earnest research to solve such problems.
【０００６】[0006]
【課題を解決するための手段】すなわち本発明は、硝酸
イソソルビドを含有する粘着性組成物からなる粘着剤層
が柔軟な担持体の上に形成されてなる貼付剤であって、
該粘着性組成物が主としてシリコーン系粘着剤（Ａ）、
ポリ酢酸ビニル系粘着剤（Ｂ）、可塑化作用成分
（Ｃ）、流動化防止成分（Ｄ）と硝酸イソソルビド
（Ｅ）との混合物であり、各成分の重量比率が、下記式
［１］、［２］、［３］、および［４］ Ａ：Ｂ＝８５：１５〜０：１００ ［１］ （Ａ＋Ｂ）：Ｃ＝９２：８〜６５：３５ ［２］ （Ａ＋Ｂ＋Ｃ）：Ｄ＝１００：０〜９５：５ ［３］ （Ａ＋Ｂ＋Ｃ＋Ｄ）：Ｅ＝８０：２０〜６５：３５ ［４］ を満足する硝酸イソソルビド含有貼付剤である。Means for Solving the Problems That is, the present invention is a patch comprising an adhesive layer comprising an adhesive composition containing isosorbide dinitrate, which is formed on a flexible carrier.
The adhesive composition is mainly a silicone-based adhesive (A),
It is a mixture of a polyvinyl acetate adhesive (B), a plasticizing component (C), a fluidization-preventing component (D) and isosorbide dinitrate (E), and the weight ratio of each component is represented by the following formula [1]: [2], [3], and [4] A: B = 85: 15 to 0: 100 [1] (A + B): C = 92: 8 to 65:35 [2] (A + B + C): D = 100: 0-95: 5 [3] (A + B + C + D): E = 80: 20-65: 35 An isosorbide dinitrate-containing patch satisfying [4].
【０００７】本発明において、シリコーン系粘着剤
（Ａ）としては、下記式［Ｉ］In the present invention, the silicone adhesive (A) is represented by the following formula [I]
【０００８】[0008]
【化２】 Embedded image
【０００９】で示される二次元構造をもった末端シラノ
ール官能直鎖状ジメチルポリシロキサン（例えばポリシ
ロキサンとして粘度約１０万〜３００万ｃｐ（２５℃）
のもの）と三次元構造のシリケートレジンの縮合反応生
成物からなる粘着剤であって、ファームテク ジャパン
７（７），５１〜５５（１９９１）に経皮吸収製剤用の
粘着剤として優れた特性をもつことが紹介されているも
のを挙げることができる。もちろん、上記一般式におい
て、Ｒおよび／又はＲ´の一部又は全部を粘着剤特性に
ほとんど影響しない範囲で、その他のアルキル基、ビニ
ル基、アルコキシ基、アリール基などで置換してもよ
い。A terminal silanol-functional linear dimethylpolysiloxane having a two-dimensional structure represented by (for example, a polysiloxane having a viscosity of about 100,000 to 3,000,000 cp (25 ° C.))
Which is a condensation reaction product of a silicate resin having a three-dimensional structure, and which has excellent properties as an adhesive for a transdermal preparation in Farm Tech Japan 7 (7), 51-55 (1991). It is possible to cite those that are introduced to have. Of course, in the above general formula, some or all of R and / or R ′ may be substituted with other alkyl groups, vinyl groups, alkoxy groups, aryl groups, etc. within a range that hardly affects the adhesive property.
【００１０】上記式［Ｉ］で表わされる本発明のシリコ
ーン系粘着剤（Ａ）の具体例としては、例えばダウコー
ニング社のＢｉｏ−ＰＳＡ（登録商標）３５５、Ｂｉｏ
−ＰＳＡ（登録商標）Ｑ７−２９２０、Ｂｉｏ−ＰＳＡ
（登録商標）Ｑ７−４５０１、東芝シリコーン社のＰＳ
Ａ６５７４等がある。本発明のシリコーン系粘着剤
（Ａ）としては、上記式［Ｉ］における骨格や置換基の
化学構造を、従来公知のカルボキシル基、アルキル基、
ビニル基、フェニル基で一部変更しても、経皮吸収性も
粘着特性も実用上ほとんど影響を受けない。従って、そ
のようなシリコーン系粘着剤、例えば通常医療用途に使
用されているものを用いることもできる。また、シリコ
ーン系粘着剤は単品でも、２種以上を混合して用いても
よい。本発明におけるシリコーン系粘着剤（Ａ）として
は、これらの中でも上記式［Ｉ］で表わされる粘着剤、
例えば、Ｂｉｏ−ＰＳＡ３５５、Ｂｉｏ−ＰＳＡＱ７−
２９２０、同Ｑ７−４５０１、ＰＳＡ６５７４等を挙げ
ることができ、より好ましくはＢｉｏ−ＰＳＡＱ７−４
５０１、同Ｑ７−２９２０が剥がれにくく、かつ除剤す
る場合に痛みが少ない点、適度なタックを有している点
が好ましいものとして挙げられる。Specific examples of the silicone adhesive (A) of the present invention represented by the above formula [I] include, for example, Bio-PSA (registered trademark) 355 and Bio-PSA (registered trademark) 355 manufactured by Dow Corning.
-PSA (registered trademark) Q7-2920, Bio-PSA
(Registered trademark) Q7-4501, PS of Toshiba Silicone Co., Ltd.
There are A6574 etc. As the silicone-based adhesive (A) of the present invention, the chemical structure of the skeleton and the substituent in the above formula [I] is the same as that of a conventionally known carboxyl group, alkyl group,
Even if the vinyl group and the phenyl group are partially changed, the transdermal absorbability and the adhesive property are practically unaffected. Therefore, such a silicone-based pressure-sensitive adhesive, for example, one commonly used in medical applications can be used. The silicone-based adhesive may be used alone or in combination of two or more. Among these, as the silicone-based adhesive (A) in the present invention, the adhesive represented by the above formula [I],
For example, Bio-PSA355, Bio-PSAQ7-
2920, Q7-4501, PSA6574 and the like, and more preferably Bio-PSAQ7-4.
It is preferable that 501 and Q7-2920 are hard to peel off, there is little pain when removing the drug, and that they have appropriate tack.
【００１１】また、本発明においてポリ酢酸ビニル系粘
着剤（Ｂ）とは、例えば酢酸ビニルと（メタ）アクリル
酸アルキルエステルおよび／又は（メタ）アクリル酸と
の共重合ポリマー；酢酸ビニルとビニルブチルエーテル
などのビニルエーテル類との共重合ポリマーなどをい
い、少なくとも酢酸ビニルの共重合比率が５０重量％以
上の共重合ポリマー等をいう。ここで（メタ）アクリル
酸アルキルエステルとしては、（メタ）アクリル酸の平
均炭素数３〜１４のアルキルエステルが好ましく、これ
らの例としては、例えばブチル（メタ）アクリレート、
アミル（メタ）アクリレート、ヘキシル（メタ）アクリ
レート、ヘプチル（メタ）アクリレート、オクチル（メ
タ）アクリレート、ノニル（メタ）アクリレート、デシ
ル（メタ）アクリレート、２−エチルヘキシル（メタ）
アクリレート等を挙げることができる。本発明のポリ酢
酸ビニル系粘着剤（Ｂ）としては、前記の中でも酢酸ビ
ニルと（メタ）アクリル酸アルキルエステルおよび／又
は（メタ）アクリル酸との共重合ポリマーが好ましく、
なかでも特に酢酸ビニルと（メタ）アクリル酸の平均炭
素数３〜１４のアルキルエステル、および／又は（メ
タ）アクリル酸との共重合ポリマーが好ましい。なかで
も酢酸ビニルと（メタ）アクリル酸の平均炭素数３〜１
４のアルキルエステルと（メタ）アクリル酸、具体的に
は２−エチルヘキシル（メタ）アクリレートと、（メ
タ）アクリル酸との共重合ポリマーが好ましく、これら
の場合、少なくとも酢酸ビニルの共重合比率が上記の場
合の共重合ポリマ−が好ましい。また（メタ）アクリル
酸の共重合比率は、０〜１０重量％が好ましく、特に１
〜５重量％が好ましい。なかでも共重合比率が、酢酸ビ
ニル：（メタ）アクリル酸アルキルエステルおよび／又
は（メタ）アクリル酸＝５０：５０〜９０：１０、なか
でも６０：４０〜８０：２０の範囲、さらには７０：３
０が好ましく、特に酸ビニル：（メタ）アクリル酸アル
キルエステル（なかでも、２−エチルヘキシル（メタ）
アクリレート）：（メタ）アクリル酸の共重合比率が７
０：２７．５：２．５のものを好ましいものとして挙げ
ることができる。かかるポリ酢酸ビニル系粘着剤（Ｂ）
の分子量としては、ポリスチレン換算での重量平均分子
量として１５０，０００〜８００，０００であるのが好
ましい。分子量が１５０，０００未満のものは流動化や
糊残りの点で必ずしも満足できるものではなく、また８
００，０００を越えるものは粘着力が不十分となりがち
である。なかでも分子量として２００，０００〜８０
０，０００を好ましいものとして挙げることができる。In the present invention, the polyvinyl acetate adhesive (B) is, for example, a copolymer of vinyl acetate and a (meth) acrylic acid alkyl ester and / or (meth) acrylic acid; vinyl acetate and vinyl butyl ether. And copolymers with vinyl ethers, such as copolymers having a copolymerization ratio of at least 50% by weight of vinyl acetate. Here, the (meth) acrylic acid alkyl ester is preferably an alkyl ester of (meth) acrylic acid having an average carbon number of 3 to 14, and examples thereof include butyl (meth) acrylate,
Amyl (meth) acrylate, hexyl (meth) acrylate, heptyl (meth) acrylate, octyl (meth) acrylate, nonyl (meth) acrylate, decyl (meth) acrylate, 2-ethylhexyl (meth)
Acrylate and the like can be mentioned. Among the above, the polyvinyl acetate-based pressure-sensitive adhesive (B) of the present invention is preferably a copolymer of vinyl acetate and a (meth) acrylic acid alkyl ester and / or (meth) acrylic acid.
Among them, a copolymer of vinyl acetate and an alkyl ester of (meth) acrylic acid having an average carbon number of 3 to 14 and / or (meth) acrylic acid is particularly preferable. Among them, vinyl acetate and (meth) acrylic acid have an average carbon number of 3 to 1
4 is preferably a copolymer of an alkyl ester of 4 and (meth) acrylic acid, specifically 2-ethylhexyl (meth) acrylate, and (meth) acrylic acid. In these cases, the copolymerization ratio of at least vinyl acetate is above. In the case of, a copolymerized polymer is preferred. The copolymerization ratio of (meth) acrylic acid is preferably 0 to 10% by weight, and particularly 1
~ 5% by weight is preferred. Among them, the copolymerization ratio is vinyl acetate: (meth) acrylic acid alkyl ester and / or (meth) acrylic acid = 50: 50 to 90:10, especially 60:40 to 80:20, and further 70: Three
0 is preferable, and vinyl acetate: (meth) acrylic acid alkyl ester (especially 2-ethylhexyl (meth))
Acrylate): (meth) acrylic acid copolymerization ratio is 7
Preferable ones are 0: 27.5: 2.5. Such polyvinyl acetate-based adhesive (B)
It is preferable that the weight average molecular weight of polystyrene is 150,000 to 800,000. If the molecular weight is less than 150,000, it is not always satisfactory in terms of fluidization and adhesive residue, and 8
If it exceeds 100,000, the adhesive strength tends to be insufficient. Above all, the molecular weight is 200,000-80
10,000 can be mentioned as a preferable thing.
【００１２】本発明においては、このようなシリコーン
系粘着剤（Ａ）とポリ酢酸ビニル系粘着剤（Ｂ）の混合
系を用いるのが好ましい。この組み合わせが優れている
点は、ＩＳＤＮの経皮吸収性が極めて高く、皮膚刺激が
少ないという点である。前記のように、ＩＳＤＮ含有貼
付剤にシリコーン系粘着剤を用いることは知られてい
る。しかし、異種粘着剤の混合系については、もともと
混合しないとその性質が出しにくいゴム系粘着剤の場合
は例外として、実際にはほとんど行われていない。特
に、シリコーン系粘着剤とポリ酢酸ビニル系粘着剤の混
合系を混合して得られた貼付剤は知られていない。これ
は、両者の粘着剤は互いに使用する溶媒が異なること、
化学構造的にも非常に異なることからこれらを混合する
必然性がみられないこと等によると考えられる。In the present invention, it is preferable to use a mixed system of such a silicone adhesive (A) and a polyvinyl acetate adhesive (B). The advantage of this combination is that the percutaneous absorption of ISDN is extremely high and the skin irritation is small. As described above, it is known to use a silicone-based pressure-sensitive adhesive for ISDN-containing patches. However, the mixing system of different kinds of pressure-sensitive adhesives is rarely actually used, except for the rubber-type pressure-sensitive adhesives which are difficult to exhibit their properties unless they are originally mixed. In particular, a patch obtained by mixing a mixed system of a silicone adhesive and a polyvinyl acetate adhesive is not known. This is because both adhesives use different solvents,
It is considered that there is no inevitability to mix these because the chemical structures are very different.
【００１３】すなわち本発明においてシリコーン系粘着
剤（Ａ）とのポリ酢酸ビニル系粘着剤（Ｂ）の重量比率
は、下記式［１］ Ａ：Ｂ＝８５：１５〜０：１００ ［１］ を満足する。本発明のシリコーン系粘着剤（Ａ）とポリ
酢酸ビニル系粘着剤（Ｂ）との混合系粘着剤を用いた貼
付剤は、他の粘着剤、例えばアクリル系粘着剤を用いて
得られた貼付剤と同等以上の良好な経皮吸収性を示す。
また、皮膚に対する粘着力も良好である。これについて
は、異種の粘着剤を混合することにより、得られる混合
系粘着剤は、いわゆる海島構造となって、皮膚との接着
性およびＩＳＤＮの放出性に特異性が出るなどのメカニ
ズムが考えられる。That is, in the present invention, the weight ratio of the silicone adhesive (A) to the polyvinyl acetate adhesive (B) is represented by the following formula [1] A: B = 85: 15 to 0: 100 [1] Be satisfied. The patch using the mixed pressure-sensitive adhesive of the silicone-based pressure-sensitive adhesive (A) and the polyvinyl acetate-based pressure-sensitive adhesive (B) of the present invention is a patch obtained by using another pressure-sensitive adhesive, for example, an acrylic pressure-sensitive adhesive. Shows good transdermal absorbability equivalent to or higher than that of the drug.
It also has good adhesion to the skin. In this regard, it is considered that the mixed adhesive obtained by mixing different kinds of adhesives has a so-called sea-island structure, and the mechanism such that the adhesiveness to the skin and the release of ISDN have specificity. .
【００１４】特に、シリコーン系粘着剤（Ａ）とポリ酢
酸ビニル系粘着剤（Ｂ）を混合したものにＩＳＤＮを添
加すると、特異的に経皮吸収性が変化し、経皮吸収性の
極大値はＡとＢの混合比率（重量比）が約３０：７０の
近傍にあり、しかもその経皮吸収性は単独系の場合のそ
れの３倍近くまで上るという驚くべき効果を示す。この
極大値でなくとも、Ａ：Ｂが８５：１５〜１５：８５の
ときも、十分に混合のメリットを享受できる程度まで経
皮吸収性は上昇する。Ａ：Ｂが８５：１５を超えてＡの
比率を高めると薬剤の経皮吸収性が低下し、またＡ：Ｂ
が１５：８５を超えてＢの比率を高めると貼付剤の粘着
力が低下し、長時間安定して貼付することが幾分困難に
なりがちである。すなわち、Ａ：Ｂ＝８５：１５〜１
５：８０の重量比率が好ましく、なかでもＡ：Ｂ＝２
０：８０〜４０：６０が好ましく、特にＡ：Ｂ＝約３
０：７０が好ましい。しかしながら、重量比率で（Ａ＋
Ｂ）に対してＣ成分を、例えば（Ａ＋Ｂ）：Ｃ＝８５：
１５〜６５：３５の範囲でＣ成分を多く用いるときは
Ａ：Ｂ＝０：１００であっても得られる貼付剤の粘着力
や経皮吸収性を高めることができる。In particular, when ISDN is added to a mixture of the silicone-based adhesive (A) and the polyvinyl acetate-based adhesive (B), the transdermal absorbability is specifically changed, and the maximum transdermal absorbability is obtained. Shows a surprising effect that the mixing ratio (weight ratio) of A and B is in the vicinity of about 30:70, and that its transdermal absorbability is up to about 3 times that in the case of a single system. Even if it is not this maximum value, even when A: B is 85:15 to 15:85, the transdermal absorbability is increased to such an extent that the merit of mixing can be fully enjoyed. If the ratio of A: B exceeds 85:15 and the ratio of A is increased, the transdermal absorbability of the drug decreases, and A: B
When the ratio of B exceeds 15:85 and the ratio of B is increased, the adhesive strength of the patch decreases, and it tends to be somewhat difficult to apply the patch stably for a long time. That is, A: B = 85: 15 to 1
A weight ratio of 5:80 is preferable, among which A: B = 2.
0:80 to 40:60 is preferable, and A: B is about 3 in particular.
0:70 is preferred. However, in weight ratio (A +
C component to B), for example, (A + B): C = 85:
When a large amount of component C is used in the range of 15 to 65:35, the adhesive force and transdermal absorbability of the obtained patch can be enhanced even when A: B = 0: 100.
【００１５】このようなシリコーン系粘着剤（Ａ）とポ
リ酢酸ビニル系粘着剤（Ｂ）との混合系粘着剤における
両粘着剤（Ａ）、（Ｂ）の好ましい組み合わせとして
は、シリコーン系粘着剤（Ａ）が前記式［Ｉ］で表わさ
れる粘着剤、なかでも具体的には、ダウコーニング社の
Ｂｉｏ−ＰＳＡ（登録商標）３５５、Ｂｉｏ−ＰＳＡ
（登録商標）Ｑ７−２９２０、Ｂｉｏ−ＰＳＡ（登録商
標）Ｑ７−４５０１、東芝シリコーン社のＰＳＡ６５７
４などである場合に、ポリ酢酸ビニル系粘着剤（Ｂ）が
酢酸ビニルのホモポリマー；酢酸ビニルと（メタ）アク
リル酸アルキルエステルおよび／又は（メタ）アクリル
酸との共重合ポリマー；酢酸ビニルとビニルブチルエー
テルなどのビニルエーテル類との共重合ポリマー等を挙
げることができる。A preferred combination of both adhesives (A) and (B) in the mixed adhesive of the silicone adhesive (A) and the polyvinyl acetate adhesive (B) is a silicone adhesive. (A) is an adhesive represented by the above formula [I], specifically, Bio-PSA (registered trademark) 355 and Bio-PSA manufactured by Dow Corning.
(Registered trademark) Q7-2920, Bio-PSA (registered trademark) Q7-4501, PSA657 manufactured by Toshiba Silicone Co., Ltd.
4, etc., the polyvinyl acetate-based adhesive (B) is a homopolymer of vinyl acetate; a copolymer of vinyl acetate with an alkyl ester of (meth) acrylic acid and / or (meth) acrylic acid; Examples thereof include copolymers with vinyl ethers such as vinyl butyl ether.
【００１６】この好ましい組み合わせに用いられるポリ
酢酸ビニル系粘着剤（Ｂ）のなかでも、酢酸ビニルの共
重合比率が５０重量％以上〜８０重量％以下が好まし
い。また、酢酸ビニルと組み合わせるモノマ−として
は、前記のポリ酢酸ビニル系粘着剤（Ｂ）の好適例で例
示したモノマーの組み合わせ及びその共重合比率と同じ
ものを挙げることができる。Among the polyvinyl acetate-based pressure-sensitive adhesives (B) used in this preferred combination, the copolymerization ratio of vinyl acetate is preferably 50% by weight or more and 80% by weight or less. As the monomer to be combined with vinyl acetate, the same combination of monomers and the same copolymerization ratio as those exemplified in the suitable example of the polyvinyl acetate-based pressure-sensitive adhesive (B) can be mentioned.
【００１７】本発明においては、ポリ酢酸ビニル系粘着
剤（Ｂ）とシリコーン系粘着剤（Ａ）に加えて、可塑化
作用成分（Ｃ）を用いる。ポリ酢酸ビニル系粘着剤
（Ｂ）はそれ自体での粘着力が弱く、シリコーン系粘着
剤（Ａ）を用いて粘着力を高め、そして特異的に硝酸イ
ソソルビドの経皮吸収性も高めるが、可塑化作用成分
（Ｃ）を用いた状態で硝酸イソソルビドを多く用いる
と、用いない場合よりもさらに経皮吸収性を高めること
ができる。さらに、この場合はシリコーン系粘着剤がな
くても皮膚への粘着力を高め、経皮吸収性を高めること
ができるのである。In the present invention, a plasticizing component (C) is used in addition to the polyvinyl acetate adhesive (B) and the silicone adhesive (A). The polyvinyl acetate-based adhesive (B) has a weak adhesive strength by itself, and the silicone-based adhesive (A) is used to enhance the adhesive strength, and specifically enhance the transdermal absorbability of isosorbide dinitrate. When a large amount of isosorbide dinitrate is used in the state where the chemical action component (C) is used, the transdermal absorbability can be further enhanced as compared with the case where it is not used. Further, in this case, the adhesive force to the skin can be enhanced and the transdermal absorbability can be enhanced without the silicone-based adhesive.
【００１８】本発明において用いる可塑化作用成分
（Ｃ）とは、例えばミリスチン酸、オレイル酸のような
炭素数が１２以上の飽和若しくは不飽和脂肪酸や、ミリ
スチン酸イソプロピル、オレイル酸エチルのようなその
エステル類、例えばα−トコフェロール、酢酸トコフェ
ロール、ニコチン酸トコフェロールのようなα−トコフ
ェロール、その誘導体からなる群から選ばれる１種又は
２種以上を挙げることができ、これらのうち、特にミリ
スチン酸イソプロピル、オレイル酸エチル、α−トコフ
ェロール、酢酸トコフェロール、ニコチン酸トコフェロ
ールが好ましい。Examples of the plasticizing component (C) used in the present invention include saturated or unsaturated fatty acids having 12 or more carbon atoms such as myristic acid and oleic acid, and isopropyl myristate and ethyl oleate. Esters, for example, α-tocopherol, tocopherol acetate, α-tocopherol such as tocopherol nicotinate, and one or more selected from the group consisting of derivatives thereof may be mentioned, and among them, isopropyl myristate is particularly preferable. Ethyl oleate, α-tocopherol, tocopherol acetate, and tocopherol nicotinate are preferred.
【００１９】かかる可塑化作用成分（Ｃ）は、それ自体
は粘着力をもたないが、シリコーン系粘着剤（Ａ）とポ
リ酢酸ビニル系粘着剤（Ｂ）の混合系粘着剤等に添加す
ることにより、粘着剤を可塑化させ、粘着性組成物の粘
着力を調整する作用も有する。また、それに加えて硝酸
イソソルビドの経皮吸収性を高めるという効果を有す
る。Such a plasticizing component (C) does not have an adhesive force by itself, but is added to a mixed adhesive such as a silicone adhesive (A) and a polyvinyl acetate adhesive (B). By doing so, it also has the function of plasticizing the pressure-sensitive adhesive and adjusting the adhesive strength of the pressure-sensitive adhesive composition. In addition to that, it has the effect of increasing the transdermal absorbability of isosorbide dinitrate.
【００２０】本発明においては、かかるシリコーン系粘
着剤（Ａ）、ポリ酢酸ビニル系粘着剤（Ｂ）と可塑化作
用成分（Ｃ）との重量比率が、下記式［２］ （Ａ＋Ｂ）：Ｃ＝９２：８〜６５：３５ ［２］ を満足する。９２：８より可塑化作用成分（Ｃ）の比率
が少ないときは、可塑化効果は不十分である。また、６
５：３５を超えて可塑化作用成分（Ｃ）を用いると、流
動化防止成分（Ｄ）をいくら用いても、粘着性組成物の
流動化、すなわち、ヒトに貼付したときに貼付剤から粘
着性組成分が流れ出したように貼付剤の周辺部にしみ出
し、これが貼付中に衣類等から発生したゴミを付着させ
て黒ずみを生じたり、また貼付剤除剤後も、貼付部位の
周辺で残留の粘着剤によるベタツキ感があるなどの現象
を起こす。なかでもシリコーン系粘着剤（Ａ）、ポリ酢
酸ビニル系粘着剤（Ｂ）と可塑化作用成分（Ｃ）の重量
比率が（Ａ＋Ｂ）：Ｃ＝９０：１０〜６５：３５である
場合が好ましく、なかでも（Ａ＋Ｂ）：Ｃ＝８５：１５
〜７０：３０である場合が好ましい。In the present invention, the weight ratio of the silicone adhesive (A), the polyvinyl acetate adhesive (B) and the plasticizing component (C) is represented by the following formula [2] (A + B): C. = 92: 8 to 65:35 [2] is satisfied. When the ratio of the plasticizing component (C) is less than 92: 8, the plasticizing effect is insufficient. Also, 6
When the plasticizing component (C) is used in an amount of more than 5:35, no matter how much the fluidization-preventing component (D) is used, the adhesive composition is fluidized, that is, it is adhered from the patch when applied to a human. The bleeding composition oozes out to the periphery of the patch, which causes dust generated from clothing etc. to adhere to the area during the application, resulting in darkening, and even after removing the patch, it remains around the application site. It causes a phenomenon such as sticky feeling caused by the adhesive. Among them, it is preferable that the weight ratio of the silicone adhesive (A), the polyvinyl acetate adhesive (B) and the plasticizing component (C) is (A + B): C = 90: 10 to 65:35, Above all (A + B): C = 85: 15
The case of ˜70: 30 is preferable.
【００２１】本発明において、シリコーン系粘着剤
（Ａ）、ポリ酢酸ビニル系粘着剤（Ｂ）、可塑化作用成
分（Ｃ）を特定の割合で用いる他、さらに流動化防止成
分（Ｄ）を用いる。シリコーン系粘着剤（Ａ）、ポリ酢
酸ビニル系粘着剤（Ｂ）、可塑化作用成分（Ｃ）と流動
化防止成分（Ｄ）の重量比率は下記式［３］ （Ａ＋Ｂ＋Ｃ）：Ｄ＝１００：０〜９５：５ ［３］ を満足する。シリコーン系粘着剤（Ａ）、ポリ酢酸ビニ
ル系粘着剤（Ｂ）、可塑化作用成分（Ｃ）に流動化防止
成分（Ｄ）を加えることにより、粘着力を適度に制御
し、経皮吸収性を高めることができるが、この粘着性組
成分から貼付剤を得た場合、特に粘着層が厚くなったと
きには、ヒトに貼付中に、貼付剤の切断面から粘着性組
成分がにじみ出し、これにより貼付剤の周辺部が黒く汚
れたり、また、にじみ出した粘着性組成分が貼付剤除剤
後も皮膚に残留し（糊残りとも言われる）、ベトツキ感
を与える。流動化防止成分（Ｄ）を加えることにより、
この黒ずみやベトツキを防止できるのである。In the present invention, the silicone adhesive (A), the polyvinyl acetate adhesive (B) and the plasticizing component (C) are used in a specific ratio, and further a fluidization preventing component (D) is used. . The weight ratio of the silicone-based pressure-sensitive adhesive (A), the polyvinyl acetate-based pressure-sensitive adhesive (B), the plasticizing component (C) and the fluidization preventing component (D) is represented by the following formula [3] (A + B + C): D = 100: 0 to 95: 5 [3] is satisfied. By adding the fluidization-preventing component (D) to the silicone-based pressure-sensitive adhesive (A), polyvinyl acetate-based pressure-sensitive adhesive (B), and plasticizing component (C), the adhesive force is appropriately controlled and transdermal absorbability is obtained. However, when a patch is obtained from this adhesive composition, especially when the adhesive layer becomes thick, the adhesive composition oozes out from the cut surface of the patch during application to a human, and The peripheral part of the patch is stained black, and the sticky composition that oozes out remains on the skin even after the patch is removed (also referred to as adhesive residue), giving a sticky feeling. By adding the fluidization preventing component (D),
This darkening and stickiness can be prevented.
【００２２】ここで、用いるポリ酢酸ビニル系粘着剤
（Ｂ）として、重量平均分子量が２５０，０００以上の
ものを用い、かつ（Ａ＋Ｂ）：Ｃ＝９２：８〜７０：３
０のときは、流動化が比較的小さくなるので（Ａ＋Ｂ＋
Ｃ）：Ｄ＝１００：０であってもよい。なかでもシリコ
ーン系粘着剤（Ａ）、ポリ酢酸ビニル系粘着剤（Ｂ）、
可塑化作用成分（Ｃ）、および流動化防止成分（Ｄ）の
重量比率としては、（Ａ＋Ｂ＋Ｃ）：Ｄ＝９９．９：
０．１〜９８：２を好ましいものとして挙げることがで
きる。（Ａ＋Ｂ＋Ｃ）：Ｄ＝９８：２を越えてＤ成分を
多く用いると、粘着性組成物がゲル状になりがちであ
り、均一な粘着層を得るための塗工がやや困難になりが
ちである。The polyvinyl acetate-based pressure-sensitive adhesive (B) used here has a weight average molecular weight of 250,000 or more, and (A + B): C = 92: 8 to 70: 3.
At 0, fluidization is relatively small, so (A + B +
C): D may be 100: 0. Among them, silicone adhesive (A), polyvinyl acetate adhesive (B),
The weight ratio of the plasticizing component (C) and the fluidization preventing component (D) is (A + B + C): D = 99.9:
0.1 to 98: 2 can be mentioned as a preferable example. When (A + B + C): D = 98: 2 is exceeded and a large amount of component D is used, the pressure-sensitive adhesive composition tends to form a gel, and the coating for obtaining a uniform pressure-sensitive adhesive layer tends to be slightly difficult. .
【００２３】本発明で用いる流動化防止成分（Ｄ）と
は、例えばポリビニルピロリドン；２〜３価の金属の有
機金属塩、又は金属キレート化合物；多価金属塩、１分
子中にカルボキシル基と反応する官能基を２つ以上有す
る多官能化合物等からなる群より選ばれる１種又は２種
以上を挙げることができる。ここで２〜３価の金属の有
機金属塩、又は金属キレート化合物としては、例えば酢
酸カルシウム、酢酸マグネシウム、アルミニウムトリス
（アセチルアセトネ−ト）等を挙げることができる。ま
たポリビニルピロリドンとしては、分子量１０，０００
以上のもので、分子量が高いほど流動化防止効果が大き
く、平均分子量１６０，０００以上の、例えばポリビニ
ルピロリドン、例えばＰＶＰ Ｋ−６０、ＰＶＰ Ｋ−
９０等を好ましいものとして挙げることができる。これ
らのなかでも、ポリビニルピロリドン、酢酸カルシウム
等の２〜３価の金属の有機金属塩、又は金属キレート化
合物は皮膚刺激性を悪化させなという点で好ましく、特
にポリビニルピロリドンは有機溶媒に溶けやすく、また
その他の粘着剤成分とも相溶しやすく、しかも流動化防
止効果も大きく、安全性も高いため、特に好ましい。The fluidization-preventing component (D) used in the present invention is, for example, polyvinylpyrrolidone; an organometallic salt of a divalent to trivalent metal, or a metal chelate compound; a polyvalent metal salt, which reacts with a carboxyl group in one molecule. One or more kinds selected from the group consisting of polyfunctional compounds having two or more functional groups to be mentioned. Examples of the organic metal salt of a divalent or trivalent metal or the metal chelate compound include calcium acetate, magnesium acetate, aluminum tris (acetylacetonate) and the like. Polyvinylpyrrolidone has a molecular weight of 10,000.
Among these, the higher the molecular weight, the greater the fluidization preventing effect, and the average molecular weight of 160,000 or more, such as polyvinylpyrrolidone, such as PVP K-60, PVP K-.
90 and the like can be mentioned as preferable ones. Among these, polyvinylpyrrolidone, an organometallic salt of a divalent or trivalent metal such as calcium acetate, or a metal chelate compound is preferable in that it does not deteriorate skin irritation, and particularly polyvinylpyrrolidone is easily dissolved in an organic solvent, In addition, it is particularly preferable because it is easily compatible with other pressure-sensitive adhesive components, has a large fluidization preventing effect, and has high safety.
【００２４】本発明においては、硝酸イソソルビド
（Ｅ）を高濃度で、しかも粘着性組成物中に溶解状態
で、すなわち、結晶が析出していない状態で用いること
ができる点も特徴の１つであり、シリコーン系粘着剤
（Ａ）、ポリ酢酸ビニル系粘着剤（Ｂ）、可塑化作用成
分（Ｃ）、流動化防止成分（Ｄ）、硝酸イソソルビド
（Ｅ）の重量比率が下記式［４］ （Ａ＋Ｂ＋Ｃ＋Ｄ）：Ｅ＝８０：２０〜６５：３５ ［４］ を満足する。硝酸イソソルビド（Ｅ）の重量比率が、こ
の比率８０：２０より小さくなると、経皮吸収性はその
比率に応じて低下する。また６５：３５より大きくなっ
ても、それに応じては経皮吸収性は向上せず、一方で粘
着力の低下、流動化の増大が起こり、好ましくない。硝
酸イソソルビドを粘着性組成物中にこれ程の高濃度で、
しかも溶解状態で保持させることができ、しかも高い経
皮吸収性と、少ない糊残りの貼付剤とできるのは驚きで
ある。One feature of the present invention is that isosorbide dinitrate (E) can be used in a high concentration and in a dissolved state in the adhesive composition, that is, in a state where crystals are not precipitated. Yes, the weight ratio of the silicone-based adhesive (A), the polyvinyl acetate-based adhesive (B), the plasticizing component (C), the fluidization-preventing component (D), and isosorbide dinitrate (E) is represented by the following formula [4]. (A + B + C + D): E = 80: 20 to 65:35 [4] is satisfied. When the weight ratio of isosorbide dinitrate (E) is smaller than this ratio of 80:20, the transdermal absorbability decreases according to the ratio. Further, when it is larger than 65:35, the transdermal absorbability is not improved accordingly, while the adhesive strength is decreased and the fluidization is increased, which is not preferable. Isosorbide dinitrate at such a high concentration in the adhesive composition,
Moreover, it is surprising that the patch can be retained in a dissolved state, has high transdermal absorbability, and has a small amount of adhesive residue.
【００２５】本発明におけるシリコーン系粘着剤
（Ａ）、ポリ酢酸ビニル系粘着剤（Ｂ）、可塑化作用成
分（Ｃ）、流動化防止成分（Ｄ）および硝酸イソソルビ
ド（Ｅ）の好ましい重量比率の組み合わせとしては、下
記式［１´］、［２´］、［３´］、および［４´］ Ａ：Ｂ＝８５：１５〜１５：８５ ［１´］ （Ａ＋Ｂ）：Ｃ＝９０：１０〜６５：３５ ［２´］ （Ａ＋Ｂ＋Ｃ）：Ｄ＝９９．９：０．１〜９５：５ ［３´］ （Ａ＋Ｂ＋Ｃ＋Ｄ）：Ｅ＝６５：３５ ［４´］ を満足する場合を挙げることができる。また本発明にお
いては、可塑化作用成分（Ｃ）を（Ａ＋Ｂ）成分８５に
対して１５以上用いるときは、Ａ成分の比率を０として
もよい。すなわち、下記式［１”］、［２”］、
［３”］、および［４”］ Ａ：Ｂ＝８５：１５〜０：１００ ［１”］ （Ａ＋Ｂ）：Ｃ＝８５：１５〜６５：３５ ［２”］ （Ａ＋Ｂ＋Ｃ）：Ｄ＝９９．９：０．１〜９５：５ ［３”］ （Ａ＋Ｂ＋Ｃ＋Ｄ）：Ｅ＝８０：２０〜６５：３５ ［４”］ を満足する場合も本発明の好ましい場合である。A preferred weight ratio of the silicone adhesive (A), the polyvinyl acetate adhesive (B), the plasticizing component (C), the anti-fluidization component (D) and the isosorbide dinitrate (E) in the present invention. As a combination, the following formulas [1 ′], [2 ′], [3 ′], and [4 ′] A: B = 85: 15 to 15:85 [1 ′] (A + B): C = 90: 10 ˜65: 35 [2 ′] (A + B + C): D = 99.9: 0.1 to 95: 5 [3 ′] (A + B + C + D): E = 65: 35 [4 ′] it can. Further, in the present invention, when the plasticizing component (C) is used in an amount of 15 or more with respect to the component (A + B) 85, the ratio of the component A may be 0. That is, the following formulas [1 ″], [2 ″],
[3 ″] and [4 ″] A: B = 85: 15 to 0: 100 [1 ″] (A + B): C = 85: 15 to 65:35 [2 ″] (A + B + C): D = 99. The case of satisfying 9: 0.1 to 95: 5 [3 ″] (A + B + C + D): E = 80: 20 to 65:35 [4 ″] is also a preferred case of the present invention.
【００２６】本発明の貼付剤は、例えば以下に説明する
方法で製造することができる。本発明においては、シリ
コーン系粘着剤（Ａ）、ポリ酢酸ビニル系粘着剤
（Ｂ）、可塑化作用成分（Ｃ）および流動化防止成分
（Ｄ）を、酢酸エチル、ヘキサン、クロロホルム、キシ
レン、トルエン、ヘキサン、アセトン、メタノール等の
単独若しくは混合溶媒に溶解若しくは分散させて得られ
る粘着剤溶液又は分散液に、ＩＳＤＮ（Ｅ）を混合し、
該粘着剤溶液又は分散液を離型紙若しくは離型フィルム
の上に乾燥後の厚みが所定の厚み、例えば５〜１００μ
ｍとなるように塗工し、次いで乾燥させて粘着剤層より
溶媒を十分に除いてＩＳＤＮ（Ｅ）を含有する粘着剤層
を得る。次いで、粘着剤層を柔軟な担持体の上に直接塗
工しなかった場合には、かかる粘着剤層を柔軟な支持体
に圧着して取付け、所望の大きさに裁断し密封包装する
ことにより貼付剤を得ることができる。The patch of the present invention can be produced, for example, by the method described below. In the present invention, the silicone-based adhesive (A), the polyvinyl acetate-based adhesive (B), the plasticizing component (C) and the fluidization-preventing component (D) are used as ethyl acetate, hexane, chloroform, xylene and toluene. ISDN (E) is mixed with a pressure-sensitive adhesive solution or dispersion obtained by dissolving or dispersing in a single solvent or a mixed solvent such as hexane, acetone, or methanol.
The pressure-sensitive adhesive solution or dispersion is dried on a release paper or a release film to have a predetermined thickness, for example, 5 to 100 μm.
m is applied and then dried to sufficiently remove the solvent from the pressure-sensitive adhesive layer to obtain a pressure-sensitive adhesive layer containing ISDN (E). Then, when the pressure-sensitive adhesive layer is not directly coated on the flexible carrier, the pressure-sensitive adhesive layer is attached to the flexible support by pressure bonding, cut into a desired size, and hermetically packaged. A patch can be obtained.
【００２７】本発明の特に好ましい貼付剤は、上記製法
において、粘着剤溶液にＩＳＤＮを混合せずに、又は十
分な量は混合せずに塗工し乾燥させた場合に得られる。
十分な量とは、実質的に薬効を発揮しない量をいう。す
なわち、公知の如く、最終貼付剤中の残留溶媒が少ない
ほど、具体的には１００ｐｐｍ以下、好ましくは５０ｐ
ｐｍ以下の残留溶媒量となるほど、貼付剤の皮膚刺激は
少なくなる。したがって、かかる残留溶媒の少ない貼付
剤を得るためには、粘着剤溶液又は分散液を離型フィル
ム等の上に塗工し、乾燥するときに十分な熱をかける
か、十分な乾燥時間をとるか、もしくは得られた粘着層
を加温したり、減圧下に置く等して、残留溶液を減少さ
せることが望ましい。ＩＳＤＮは昇華性を有する薬物で
あるため、ＩＳＤＮを含有していないか、十分には含有
しない粘着剤層の場合、ＩＳＤＮが昇華することに全く
配慮する必要がなくなり、十分に残留溶媒の少ない粘着
層を容易に作ることができるのである。The particularly preferred patch of the present invention is obtained by applying and drying ISDN in the pressure-sensitive adhesive solution without mixing it or in a sufficient amount in the above-mentioned production method.
The sufficient amount means an amount that does not substantially exert a medicinal effect. That is, as is known, the less the residual solvent in the final patch, the more specifically 100 ppm or less, preferably 50 p.
The lower the residual solvent amount is pm, the less skin irritation of the patch will be. Therefore, in order to obtain such a patch with less residual solvent, a pressure-sensitive adhesive solution or dispersion is applied onto a release film or the like, and sufficient heat is applied when drying or a sufficient drying time is taken. Alternatively, it is desirable to reduce the residual solution by heating the obtained adhesive layer or placing it under reduced pressure. Since ISDN is a sublimable drug, in the case of an adhesive layer that does not contain ISDN or does not contain it sufficiently, it is not necessary to pay attention to the fact that ISDN sublimes. The layers can be made easily.
【００２８】従って、本発明の好ましい貼付剤の製造法
の１つにおいては、特開昭４８−１５３８８号公報や特
開平３−２４６２１９号公報と同じ原理で、まずＩＳＤ
Ｎを混合せずに、又は十分な量は混合せずに粘着剤溶液
又は分散液を塗工してＩＳＤＮを含有しないか、又は十
分には含有しない粘着剤層を得、次にこの粘着剤層にア
セトン、メタノール、エタノール、酢酸エチル等の揮発
性の高い溶媒に高濃度に溶解したＩＳＤＮ溶液を直接若
しくはフィルム；編物、織物、不織布等の布帛；これら
の複合物などを介して間接的に滴下、スプレー、塗布、
又は浸漬等することにより、所望量のＩＳＤＮを付着さ
せる。次に、長時間放置、又は加温などによりＩＳＤＮ
をかかる粘着剤層に拡散させて、貼付剤を得ることがで
きる。Therefore, in one of the preferred methods for producing a patch of the present invention, the ISD is first used in accordance with the same principle as in JP-A-48-15388 and JP-A-3-246219.
A pressure-sensitive adhesive solution or dispersion is applied without mixing N or in a sufficient amount to obtain a pressure-sensitive adhesive layer that does not contain ISDN or does not sufficiently contain ISDN. The ISDN solution dissolved in a highly volatile solvent such as acetone, methanol, ethanol, ethyl acetate, etc. at a high concentration is directly applied to the layer, or a film; a fabric such as a knitted fabric, a woven fabric or a non-woven fabric; indirectly through a composite of these. Dripping, spraying, applying,
Alternatively, a desired amount of ISDN is attached by dipping or the like. Next, leave ISDN for a long time or by heating.
Can be diffused into the pressure-sensitive adhesive layer to obtain a patch.
【００２９】塗工・乾燥して粘着剤層を作る場合に用い
る溶媒とＩＳＤＮを溶解するときに用いる溶媒が同じで
あっても、ＩＳＤＮを溶解するのにこの溶媒を用いて前
記説明の方法で貼付剤を得る場合の方が、はるかに容易
に貼付剤の残留溶媒を少なくすることができる。Even if the solvent used for preparing the pressure-sensitive adhesive layer by coating and drying is the same as the solvent used for dissolving ISDN, this solvent is used for dissolving ISDN by the method described above. It is much easier to reduce the residual solvent in the patch when obtaining the patch.
【００３０】本発明において、粘着性組成物には、前記
Ａ〜Ｅ成分のほか、これらの組成物の特性に実用上影響
しない範囲で、その他の粘着剤、例えばゴム系粘着剤、
ビニルエーテル系粘着剤の単独又は混合物を併用しても
よく、必要に応じて公知の吸収促進剤、溶解助剤、拡散
助剤、充填剤などを単独又は混合にて含有させてもよ
い。In the present invention, the pressure-sensitive adhesive composition contains, in addition to the above-mentioned components A to E, other pressure-sensitive adhesives such as rubber-based pressure-sensitive adhesives within a range not practically affecting the characteristics of these compositions.
The vinyl ether-based pressure-sensitive adhesives may be used alone or in combination, and if necessary, known absorption promoters, dissolution aids, diffusion aids, fillers and the like may be contained alone or in a mixture.
【００３１】吸収促進剤又は拡散助剤としては、例え
ば、ラウリル硫酸ナトリウム、ドデシルベンゼンスルフ
ォン酸ナトリウム、アルキルジフェニルエーテルジスル
フォン酸ナトリウム、ジオクチルスルホコハク酸塩、ポ
リオキシアルキルフェニルエーテルサルフェートアンモ
ニウム塩などの界面活性剤；グリセリン、ジエチレング
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、高級脂肪族アルコールなどのアルコール類；ジメ
チルスルホキシドおよびアルキルメチル誘導体；サリチ
ル酸、尿素、ジメチルアセトアミド、ジメチルホルムア
ミド、ラノリン、アラントイン、スクアレン、カーボポ
ール、ジイソプロピルアジペート、ピログルタミン酸ラ
ウリルエステル、エチルラウレート、ニコチン酸メチ
ル、ソルビトールおよびドデシルピロリドンのようなピ
ロリドン誘導体、オリーブ油、ヒマシ油、流動パラフィ
ン、ワセリン、ゼラチン、アミノ酸、乳酸、乳酸エチ
ル、ニコチン酸ベンジル、Ｌ−メントール、カンファ
ー、ドデシルアザシクロヘプタン−２−オンなどを用い
ることができる。かかる添加剤は、ＩＳＤＮ１重量部当
たり、０．０５〜５重量部用いるのがよい。Examples of the absorption enhancer or diffusion aid include surfactants such as sodium lauryl sulfate, sodium dodecylbenzene sulfonate, sodium alkyldiphenyl ether disulphonate, dioctyl sulfosuccinate and polyoxyalkylphenyl ether sulfate ammonium salt. Alcohols such as glycerin, diethylene glycol, propylene glycol, polyethylene glycol, higher aliphatic alcohols; dimethyl sulfoxide and alkylmethyl derivatives; salicylic acid, urea, dimethylacetamide, dimethylformamide, lanolin, allantoin, squalene, carbopol, diisopropyl adipate, pyro Glutamic acid lauryl ester, ethyl laurate, methyl nicotinate, sorbitol and Pyrrolidone derivatives such as dodecylpyrrolidone, olive oil, castor oil, liquid paraffin, petrolatum, gelatin, amino acids, lactic acid, ethyl lactate, benzyl nicotinate, L-menthol, camphor, dodecylazacycloheptan-2-one can be used. it can. It is preferable to use such an additive in an amount of 0.05 to 5 parts by weight per 1 part by weight of ISDN.
【００３２】本発明の貼付剤においては、ＩＳＤＮ
（Ｅ）を含有する粘着性組成物からなる粘着剤層は、柔
軟な担持体の上に形成されるが、かかる柔軟な担持体と
しては、例えばフィルム；織物、編物、不織布等の布
帛；又はこれらフィルムと布帛の複合物などが用いられ
る。かかるフィルムや布帛の材質としては、ポリエチレ
ンテレフタレートのようなポリエステル；ポリエチレ
ン、ポリプロピレンのようなポリオレフィン；ナイロン
６のようなポリアミド；エチレン−酢酸ビニル共重合体
などを用いることができる。かかる材質の中でも、安定
性、安全性の面からポリエステルが好ましい。In the patch of the present invention, ISDN
The pressure-sensitive adhesive layer composed of the pressure-sensitive adhesive composition containing (E) is formed on a flexible carrier, and examples of such a flexible carrier include a film; a fabric such as a woven fabric, a knitted fabric, and a nonwoven fabric; or A composite of these films and cloth is used. As a material for such a film or cloth, polyester such as polyethylene terephthalate; polyolefin such as polyethylene or polypropylene; polyamide such as nylon 6; ethylene-vinyl acetate copolymer and the like can be used. Among these materials, polyester is preferable in terms of stability and safety.
【００３３】特に、貼付剤からＩＳＤＮが逃散しにくく
安定性が高い柔軟な担持体としてフィルムを用いる場合
には、貼付剤の取扱性を改善する目的で、該フィルムの
内側または外側面に接着剤（又は粘着剤）を介して、例
えば織物、編物、不織布等の布帛を取付ける態様をとる
とき、得られる貼付剤の取扱性も良好となる。そのよう
な担持体としては、フィルムの厚みが０．５〜１０μ
ｍ、布帛は目付けが８〜１００ｇ／ｍ2 であるのが好ま
しく、特にフィルムが厚み０．５〜４．９μｍのポリエ
ステルフィルムで、布帛が目付け８〜３０ｇ／ｍ2 のポ
リエステルであるときが好ましい。In particular, when the film is used as a flexible carrier having high stability in which ISDN does not easily escape from the patch, an adhesive is applied to the inner or outer surface of the film for the purpose of improving the handleability of the patch. When a fabric such as a woven fabric, a knitted fabric, or a non-woven fabric is attached via (or a pressure-sensitive adhesive), the obtained patch has good handleability. As such a carrier, the film thickness is 0.5 to 10 μm.
m, the fabric preferably has a basis weight of 8 to 100 g / m 2 , and particularly preferably the film is a polyester film having a thickness of 0.5 to 4.9 μm and the fabric has a basis weight of 8 to 30 g / m 2. .
【００３４】特に好ましい貼付剤の態様を以下に示す。
すなわち、貼付剤が、 （ａ）フィルム層 （ｂ）接着剤層 （ｃ）布帛 （ｄ）接着剤層 （ｅ）フィルム層 （ｆ）薬物含有粘着性組成物 （ｇ）離型フィルム層 からなり、最外層が（ａ）であり、（ａ）、（ｂ）、
（ｃ）、（ｄ）、（ｅ）、（ｆ）、（ｇ）の順に積層し
てあり、使用時には（ｇ）は捨てる。A particularly preferred embodiment of the patch is shown below.
That is, the patch comprises (a) film layer, (b) adhesive layer, (c) cloth, (d) adhesive layer, (e) film layer, (f) drug-containing adhesive composition (g) release film layer, , The outermost layer is (a), (a), (b),
(C), (d), (e), (f), and (g) are laminated in this order, and (g) is discarded when used.
【００３５】（ａ）と（ｅ）は厚みが０．５〜４．９μ
ｍのポリエステルフィルム層であり、フィルムとして
は、例えば極薄ポリエステルフィルム（商品名、テイジ
ン テトロンフィルム ＨＴタイプ又はＦタイプ）が特
に好ましい。（ａ）と（ｅ）は同じでもよく、異なって
いてもよい。（ｂ）および（ｄ）は厚みが５〜４０μｍ
の接着剤層であり、例えばシリコーン系粘着剤、アクリ
ル系粘着剤、ゴム系粘着剤、ポリ酢酸ビニル系粘着剤又
はエチレン−酢酸ビニル共重合体系接着剤などの単独又
は混合系からなり、ここで（ｂ）と（ｄ）は同じでもよ
く、異なっていてもよく、（ｂ）と（ｄ）とが一層でそ
の役割をもってもよい。（ｃ）は目付が８〜３０ｇ／ｍ
2 のポリエステル編物（帝人株式会社製 ＫＺ００７８
−Ｇ）である。（ｆ）は前記のような本発明の粘着剤組
成物であり、厚みが１０〜７０μｍであり、（ｇ）はシ
リコーン樹脂をコーティングした厚み３０〜１００μｍ
のポリエステルフィルム系離型フィルム層である。The thickness of (a) and (e) is 0.5 to 4.9 μm.
m is a polyester film layer, and as the film, for example, an extremely thin polyester film (trade name, Teijin Tetoron film HT type or F type) is particularly preferable. (A) and (e) may be the same or different. (B) and (d) have a thickness of 5 to 40 μm
An adhesive layer of, for example, a silicone-based adhesive, an acrylic-based adhesive, a rubber-based adhesive, a polyvinyl acetate-based adhesive or an ethylene-vinyl acetate copolymer-based adhesive, or a single or mixed system, wherein (B) and (d) may be the same or different, and (b) and (d) may be one layer and have the role. (C) has a basis weight of 8 to 30 g / m
2 polyester knits (KZ0078 manufactured by Teijin Limited)
-G). (F) is the pressure-sensitive adhesive composition of the present invention as described above, having a thickness of 10 to 70 μm, and (g) is a silicone resin-coated thickness of 30 to 100 μm.
Is a polyester film-based release film layer.
【００３６】このような特に好ましい貼付剤において
（ａ）フィルム層のポリエステルフィルムとしては、
０．５〜４．０μｍの範囲のものが強度、取扱い性、皮
膚カブレ、密封性の点で好ましい。０．５μｍ未満では
強度、取扱い性等が不十分である場合があり、また４．
９μｍを超えると皮膚への追従性、皮膚カブレなどの点
で問題がある場合がある。また、（ｃ）布帛としては、
目付８〜３０ｇ／ｍ2 のものが皮膚カブレ、取扱い性の
点で好ましいが、さらに１０〜２０ｇ／ｍ2 のものが薬
物の拡散性、吸収性に優れているので好ましい。さら
に、（ｂ）と（ｄ）の接着剤としては、アクリル系粘着
剤としては、少なくとも８０〜９８重量％の２−エチル
ヘキシルアクリレ−トと２０〜２重量％の（メタ）アク
リル酸の共重合体が好ましく、なかでも、少なくとも８
０〜９８重量％の２−エチルヘキシルアクリレ−ト、２
０〜２重量％メタアクリル酸とアクリル酸、特に９０重
量％の２−エチルヘキシルアクリレ−ト、７重量％メタ
アクリル酸と３重量％アクリル酸の共重合体が好まし
い。またゴム系粘着剤、シリコ−ン系粘着剤、ポリ酢酸
ビニル系粘着剤又はエチレン−酢酸ビニル共重合体系接
着剤としては従来公知のものを挙げることができる。In such a particularly preferred patch, the polyester film of the (a) film layer is
Those having a range of 0.5 to 4.0 μm are preferable in terms of strength, handleability, skin rash, and sealing property. If it is less than 0.5 μm, the strength and handleability may be insufficient, and 4.
If it exceeds 9 μm, there may be a problem with respect to skin followability and skin rash. Further, as the (c) cloth,
Basis weight 8~30g / m 2 things skin rash, although preferred in view of handling properties, preferably more that diffusion of the drug 10 to 20 g / m 2, since the excellent absorbent. Further, as the adhesive of (b) and (d), as an acrylic pressure-sensitive adhesive, a mixture of at least 80 to 98% by weight of 2-ethylhexyl acrylate and 20 to 2% by weight of (meth) acrylic acid is used. Polymers are preferred, of which at least 8
0-98% by weight of 2-ethylhexyl acrylate, 2
Copolymers of 0-2% by weight methacrylic acid and acrylic acid, especially 90% by weight 2-ethylhexyl acrylate, 7% by weight methacrylic acid and 3% by weight acrylic acid are preferred. As the rubber-based pressure-sensitive adhesive, the silicone-based pressure-sensitive adhesive, the polyvinyl acetate-based pressure-sensitive adhesive, or the ethylene-vinyl acetate copolymer-based adhesive, conventionally known ones can be mentioned.
【００３７】これらのなかでも（ａ）〜（ｆ）の好まし
い組み合わせとしては、例えば、（ａ）および（ｅ）が
約１．０〜３．５μｍのポリエステルフィルム、（ｂ）
と（ｄ）が一層で約１０〜２５μｍの接着剤層、（ｃ）
が目付が８〜２０ｇ／ｍ2 の編物、なかでも８〜２０ｇ
／ｍ2 の単糸デニールが３デニール以下（０．１〜３デ
ニール）の細いポリエステルのフィラメントからなる編
物、（ｆ）は約２５〜６０μｍの厚みの本発明の薬物含
有粘着性組成物層である。Among these, preferred combinations of (a) to (f) include, for example, polyester films in which (a) and (e) are about 1.0 to 3.5 μm, and (b).
And (d) is a single layer having an adhesive layer of about 10 to 25 μm, (c)
Is a knitted fabric having a basis weight of 8 to 20 g / m 2 , especially 8 to 20 g
/ M 2 single yarn denier is a knitted fabric composed of thin polyester filaments having a denier of 3 denier or less (0.1 to 3 denier), (f) is a drug-containing adhesive composition layer of the present invention having a thickness of about 25 to 60 μm. is there.
【００３８】[0038]
【実施例】以下に実施例を挙げて本発明をさらに詳細に
説明する。実施例中の部、％および比率はいずれも重量
基準である。実施例で用いた血中ＩＳＤＮ濃度の測定方
法、ポリ酢酸ビニル粘着剤および布帛試料の作成方法は
以下のとおりである。（１）血中ＩＳＤＮ濃度の測定方法 １ｍｌの採血血液より血漿を分離した後、４ｍｌのｎ−
ヘキサンを用いてＩＳＤＮを抽出、濃縮して、この濃縮
物に酢酸エチル１００μ酢酸エチル１００μｌを加えて
試料を得、この試料中のＩＳＤＮをＧＣ−ＥＣＤ法によ
り定量した。（２）ポリ酢酸ビニル系粘着剤（ＰＶＡ−１）の作成 ２−エチルヘキシルアクリレートとの共重合ポリマーを
用い、以下の方法により合成した。すなわち、酢酸ビニ
ル７０部、２−エチルヘキシルアクリレート２７．５
部、アクリル酸２．５部、過酸化ベンゾイル１部および
酢酸エチル１５０部を還流冷却機、かきまぜ機を有する
反応容器に仕込み、窒素雰囲気下６０℃でゆっくり攪拌
しながら、１２時間重合を続けた。重合転化率は９９．
９％であった。得られた重合体溶液中の固形分濃度は約
４０％であった。これをアクリルエステル共重合ポリ酢
酸ビニル粘着剤試料（ＰＶＡ−１）という。本品の重量
平均分子量（ポリスチレン換算）は３５６，０００であ
った。The present invention will be described in more detail with reference to the following examples. All parts, percentages and ratios in the examples are by weight. The method for measuring the blood ISDN concentration used in the examples, the method for preparing the polyvinyl acetate pressure-sensitive adhesive, and the cloth sample are as follows. (1) Method for measuring ISDN concentration in blood After separating plasma from 1 ml of blood sampled, 4 ml of n-
ISDN was extracted and concentrated using hexane, 100 µl of ethyl acetate and 100 µl of ethyl acetate were added to this concentrate to obtain a sample, and ISDN in this sample was quantified by the GC-ECD method. (2) Preparation of Polyvinyl Acetate Adhesive (PVA-1) Using a copolymer with 2-ethylhexyl acrylate, it was synthesized by the following method. That is, 70 parts of vinyl acetate and 27.5 of 2-ethylhexyl acrylate.
Parts, 2.5 parts of acrylic acid, 1 part of benzoyl peroxide and 150 parts of ethyl acetate were charged into a reaction vessel having a reflux condenser and an agitator, and polymerization was continued for 12 hours while slowly stirring at 60 ° C. under a nitrogen atmosphere. . The polymerization conversion rate is 99.
It was 9%. The solid content concentration in the obtained polymer solution was about 40%. This is called an acrylic ester copolymerized polyvinyl acetate pressure-sensitive adhesive sample (PVA-1). The weight average molecular weight (in terms of polystyrene) of this product was 356,000.
【００３９】（３）布帛試料の作成 テレフタル酸ジメチル２９７部、エチレングリコール２
６５部、３，５−ジ（カルボメトキシ）ベンゼンスルホ
ン酸ナトリウム５３部（テレフタル酸ジメチルに対して
１１．７モル％）、酢酸マンガン４水塩０．０８４部お
よび酢酸ナトリウム３水塩１．２２部を精留塔付ガスフ
ラスコに入れ、常法に従ってエステル交換反応を行い、
理論量のメタノールが留出した後、反応生成物を精留塔
付重縮合用フラスコに入れ、安定剤として正リン酸の５
６％水溶液０．０９０部および重縮合触媒として三酸化
アンチモン０．１３５部を加え、温度２７５℃で、常圧
下２０分、３０ｍｍＨｇの減圧下１５分間反応させた
後、高真空で１００分間反応させた。最終内圧は０．３
９ｍｍＨｇであり、得られた共重合ポリマーの極限粘度
は０．４０２、軟化点は約２００℃であった。反応終了
後、共重合ポリマーを常法に従いチップ化した。 (3) Fabric sample preparation 297 parts of dimethyl terephthalate, ethylene glycol 2
65 parts, 53 parts of sodium 3,5-di (carbomethoxy) benzenesulfonate (11.7 mol% relative to dimethyl terephthalate), manganese acetate tetrahydrate 0.084 parts and sodium acetate trihydrate 1.22 Parts into a gas flask with a rectification column, and conduct transesterification reaction according to a conventional method,
After the theoretical amount of methanol was distilled, the reaction product was placed in a polycondensation flask equipped with a rectification column, and 5% of orthophosphoric acid was used as a stabilizer.
A 6% aqueous solution (0.090 parts) and an antimony trioxide (0.135 parts) as a polycondensation catalyst were added, and the mixture was reacted at a temperature of 275 ° C. under normal pressure for 20 minutes and under reduced pressure of 30 mmHg for 15 minutes, and then under high vacuum for 100 minutes. It was Final internal pressure is 0.3
The copolymer had an intrinsic viscosity of 0.402 and a softening point of about 200 ° C. After completion of the reaction, the copolymerized polymer was made into chips according to a conventional method.
【００４０】この共重合ポリマーのチップ１５部と極限
粘度０．６４０のポリエチレンテレフタレートのチップ
８５部とをナウタ・ミキサー（細川鉄工所製）中で５分
間混合した後、窒素気流中にて１１０℃で２時間、さら
に１５０℃で７時間乾燥した後、二軸スクリュー式押出
機を用いて２８５℃で溶媒混練してチップ化した。この
チップの極限粘度は０．５３５、軟化点は２６１℃であ
った。このチップを常法により乾燥し、紡糸口金に幅
０．０５ｍｍ、径０．６ｍｍである円形スリットの２箇
所が閉じた円弧状の開口部をもつものを使用し、常法に
従って紡糸し、外径と内径の比が２：１の中空繊維（中
空率２５％）を作った。得られた中空繊維は、該中空繊
維断面全体に散在し、繊維方向に配列する微細孔を有
し、該微細孔はその少なくとも一部が中空部まで連通し
ていた。この原糸は１５０デニール／１２フィラメント
であり、この原糸を用い、常法に従って延伸倍率５．１
倍で延伸し、２０デニール／１２フィラメントのマルチ
フィラメントを得た。このマルチフィラメントを経編地
になし、常法により精練、乾燥後、１％カセイソーダ水
溶液でかつ沸騰温度にて２時間処理してアルカリ減量率
２０％の編物を得た。得られた編物を縦方向に１．５倍
引き延ばして、１５０℃で１分間熱をかけてヒートセッ
トして目付け１３ｇ／ｍ2 の編物、すなわち布帛試料を
得た。15 parts of this copolymerized polymer chip and 85 parts of polyethylene terephthalate chip having an intrinsic viscosity of 0.640 were mixed in a Nauta mixer (manufactured by Hosokawa Iron Works) for 5 minutes and then 110 ° C. in a nitrogen stream. After being dried for 2 hours and further at 150 ° C. for 7 hours, the mixture was kneaded with a solvent at 285 ° C. using a twin-screw extruder to form chips. This chip had an intrinsic viscosity of 0.535 and a softening point of 261 ° C. The chips were dried by a conventional method, and a spinneret having a circular slit having a width of 0.05 mm and a diameter of 0.6 mm having two circular arc-shaped openings was used. Hollow fibers (hollow ratio 25%) with a diameter to inner diameter ratio of 2: 1 were made. The obtained hollow fibers were scattered over the entire cross section of the hollow fibers and had fine pores arranged in the fiber direction, and at least a part of the fine pores communicated with the hollow portion. This yarn was 150 denier / 12 filaments, and using this yarn, the draw ratio was 5.1 according to the conventional method.
It was stretched at a doubling rate to obtain a multifilament of 20 denier / 12 filament. This multifilament was formed into a warp knitted fabric, scoured and dried by a conventional method, and then treated with a 1% caustic soda aqueous solution at a boiling temperature for 2 hours to obtain a knitted fabric having an alkali weight loss rate of 20%. The obtained knitted fabric was stretched 1.5 times in the machine direction and heated at 150 ° C. for 1 minute to heat set to obtain a knitted fabric having a basis weight of 13 g / m 2 , that is, a fabric sample.
【００４１】［実施例１〜４，比較例１〜６］ （イ）粘着性組成物の作成 シリコーン系粘着剤（Ａ）としてダウコーニング社のＢ
ｉｏ−ＰＳＡ（登録商標）３５５（固形分１８．５
％）、ポリ酢酸ビニル系粘着剤（Ｂ）としては上記
（２）で得たポリ酢酸ビニル系粘着剤（ＰＶＡ−１）、
可塑化作用成分（Ｃ）としてはミリスチン酸イソプロピ
ル、流動化防止成分（Ｄ）としてポリビニルピロリドン
ＰＶＰ Ｋ−９０を用いた。シリコーン系粘着剤
（Ａ）、ポリ酢酸ビニル系粘着剤（Ｂ）、可塑化作用成
分（Ｃ）、流動化防止成分（Ｄ）、及び硝酸イソソルビ
ド（Ｅ）の混合比率を表１に記載のように変えて、十分
に混合しド−プとして本発明の粘着性組成物を得た。こ
のド−プを、厚み７５μのポリエチレンテレフタレート
を用いたフッ素離型フィルムの上に塗工し、乾燥後の厚
みが５７μｍの硝酸イソソルビドを含有する粘着剤層を
得た。なお、比較例４の粘着剤としては、下記（２）の
アクリル系粘着剤（ＡＰ）を用いた。 （ロ）柔軟な担持体の作成 一方、（ａ）フィルムとして、厚み１．３μｍのポリエ
チレンテレフタレートフィルム（テイジン テトロンフ
ィルム ＨＴタイプ）を用い、まず（ａ）フィルムの片
面に２−エチルヘキシルアクリル酸・メタアクリル酸メ
チル・アクリル酸（９０：７：３）の共重合体重量平均
分子量５５０，０００のアクリル系粘着剤（ＡＰ）から
なる厚み４０μの粘着層（ｂ）を圧着し、このＡＰの粘
着層の自由となっている１面に前記（３）で得た布帛試
料を圧着し、さらにこの布帛材料（ｃ）の自由となって
いる面に、さらに（ｅ）フィルムとして厚み１．３μｍ
のポリエチレンテレフタレートフィルムを圧着して担持
体を得た。 （ハ）貼付剤の作成 （ロ）で得た担持体の（ｅ）フィルムの自由となってい
る面に、（イ）で得た硝酸イソソルビドを含有する５７
μｍの粘着剤層のフッ素離型フィルムの取り付けていな
い面を圧着して積層物を得、この積層物を５．５ｃｍ×
５．５ｃｍに裁断して３０ｃｍ2 当たり４０ｍｇの硝酸
イソソルビドを含有する貼付剤を得た。 （ニ）薬理試験 かくして得られた製剤から、大きさ１０ｃｍ2 の動物試
験用の製剤を作り、除毛した平均体重２００ｇのヘアレ
スラット（ｎ＝７）の背部に貼付し、貼付前、貼付後５
時間、貼付後２４時間に採血し、それぞれ血中のＩＳＤ
Ｎ濃度を測定し、得られた血中濃度よりＣｍａｘおよび
ＡＵＣを計算した。また、皮膚との粘着状態も調べた。
結果を表１に示す。[Examples 1 to 4 and Comparative Examples 1 to 6] (a) Preparation of adhesive composition As the silicone-based adhesive (A), B of Dow Corning Co.
io-PSA (registered trademark) 355 (solid content: 18.5)
%), As the polyvinyl acetate-based adhesive (B), the polyvinyl acetate-based adhesive (PVA-1) obtained in the above (2),
Isopropyl myristate was used as the plasticizing component (C), and polyvinylpyrrolidone PVP K-90 was used as the fluidization-preventing component (D). The mixing ratios of the silicone adhesive (A), the polyvinyl acetate adhesive (B), the plasticizing component (C), the fluidization preventing component (D), and the isosorbide dinitrate (E) are as shown in Table 1. In place of the above, the mixture was thoroughly mixed to obtain a tacky composition of the present invention as a dope. This dope was applied onto a fluorine release film having a thickness of 75 μm and made of polyethylene terephthalate to obtain a pressure-sensitive adhesive layer containing dried isosorbide dinitrate having a thickness of 57 μm. As the pressure-sensitive adhesive of Comparative Example 4, the acrylic pressure-sensitive adhesive (AP) shown in (2) below was used. (B) Preparation of flexible carrier On the other hand, as a film (a), a polyethylene terephthalate film having a thickness of 1.3 μm (Teijin Tetoron film HT type) was used. First, (a) film was coated with 2-ethylhexyl acrylic acid / meth. Methyl acrylate / acrylic acid (90: 7: 3) copolymer A pressure-sensitive adhesive layer (b) having a thickness of 40 μ and made of an acrylic pressure-sensitive adhesive (AP) having a weight average molecular weight of 550,000 is pressure-bonded to the pressure-sensitive adhesive layer of this AP. The fabric sample obtained in the above (3) is pressure-bonded to one free surface of (3), and the free surface of this fabric material (c) further has a thickness of 1.3 μm as a (e) film.
The polyethylene terephthalate film of 1 was pressure-bonded to obtain a carrier. (C) Preparation of patch The isosorbide dinitrate obtained in (A) is contained on the free surface of the (e) film of the carrier obtained in (B).
The surface of the pressure-sensitive adhesive layer of μm on which the fluorine release film is not attached is pressure-bonded to obtain a laminate, and the laminate is 5.5 cm ×
It was cut into 5.5 cm to obtain a patch containing 40 mg of isosorbide dinitrate per 30 cm 2 . (D) Pharmacological test From the thus obtained preparation, a preparation for animal testing having a size of 10 cm 2 was prepared and applied to the back of a hairless rat (n = 7) with an average body weight of 200 g, before and after application. 5
Time, 24 hours after application, ISD in blood
The N concentration was measured, and Cmax and AUC were calculated from the obtained blood concentration. Also, the state of adhesion to the skin was examined.
The results are shown in Table 1.
【００４２】[0042]
【表１】 [Table 1]
Claims (12)
物からなる粘着剤層が柔軟な担持体の上に形成されてな
る貼付剤であって、該粘着性組成物が主としてシリコー
ン系粘着剤（Ａ）、ポリ酢酸ビニル系粘着剤（Ｂ）、可
塑化作用成分（Ｃ）、流動化防止成分（Ｄ）と硝酸イソ
ソルビド（Ｅ）との混合物であり、各成分の重量比率
が、下記式［１］、［２］、［３］、および［４］ Ａ：Ｂ＝８５：１５〜０：１００ ［１］ （Ａ＋Ｂ）：Ｃ＝９２：８〜６５：３５ ［２］ （Ａ＋Ｂ＋Ｃ）：Ｄ＝１００：０〜９５：５ ［３］ （Ａ＋Ｂ＋Ｃ＋Ｄ）：Ｅ＝８０：２０〜６５：３５ ［４］ を満足する硝酸イソソルビド含有貼付剤。1. A patch comprising a pressure-sensitive adhesive layer made of a pressure-sensitive adhesive composition containing isosorbide dinitrate formed on a flexible carrier, wherein the pressure-sensitive adhesive composition mainly comprises a silicone-based pressure-sensitive adhesive (A). ), A polyvinyl acetate-based pressure-sensitive adhesive (B), a plasticizing component (C), a fluidization-preventing component (D) and isosorbide dinitrate (E), and the weight ratio of each component is represented by the following formula [1. ], [2], [3], and [4] A: B = 85: 15-0: 100 [1] (A + B): C = 92: 8-65: 35 [2] (A + B + C): D = 100: 0 to 95: 5 [3] (A + B + C + D): E = 80: 20 to 65:35 An isosorbide dinitrate-containing patch satisfying [4].
ニル系粘着剤（Ｂ）の重量比率が、下記式［５］ Ａ：Ｂ＝２０：８０〜４０：６０ ［５］ を満足する請求項１記載の硝酸イソソルビド含有貼付
剤。2. The weight ratio of the silicone adhesive (A) and the polyvinyl acetate adhesive (B) satisfies the following formula [5] A: B = 20: 80 to 40:60 [5]. Item 2. An isosorbide dinitrate-containing patch according to Item 1.
ニル系粘着剤（Ｂ）と可塑化作用成分（Ｃ）の重量比率
が、下記式［６］ （Ａ＋Ｂ）：Ｃ＝８５：１５〜７０：３０ ［６］ を満足する請求項１記載の硝酸イソソルビド含有貼付
剤。3. The weight ratio of the silicone adhesive (A), the polyvinyl acetate adhesive (B) and the plasticizing component (C) is represented by the following formula [6] (A + B): C = 85: 15: 15. 70:30 The patch containing isosorbide nitrate according to claim 1, which satisfies [6].
ニル系粘着剤（Ｂ）、可塑化作用成分（Ｃ）と流動化防
止成分（Ｄ）の重量比率が、下記式［７］ （Ａ＋Ｂ＋Ｃ）：Ｄ＝９９．９：０．１〜９８：２ ［７］ を満足する請求項１記載の硝酸イソソルビド含有貼付
剤。4. The weight ratio of the silicone adhesive (A), the polyvinyl acetate adhesive (B), the plasticizing component (C) and the fluidization preventing component (D) is represented by the following formula [7] (A + B + C). ): D = 99.9: 0.1 to 98: 2 The patch containing isosorbide nitrate according to claim 1, which satisfies [7].
ニル系粘着剤（Ｂ）、可塑化作用成分（Ｃ）、流動化防
止成分（Ｄ）と硝酸イソソルビド（Ｅ）の重量比率が、
下記式［１´］、［２´］、［３´］および［４´］ Ａ：Ｂ＝８５：１５〜１５：８５ ［１´］ （Ａ＋Ｂ）：Ｃ＝９０：１０〜６５：３５ ［２´］ （Ａ＋Ｂ＋Ｃ）：Ｄ＝９９．９：０．１〜９５：５ ［３´］ （Ａ＋Ｂ＋Ｃ＋Ｄ）：Ｅ＝６５：３５ ［４´］ を満足する請求項１記載の硝酸イソソルビド含有貼付
剤。5. The weight ratio of the silicone adhesive (A), the polyvinyl acetate adhesive (B), the plasticizing component (C), the fluidization preventing component (D) and the isosorbide dinitrate (E) is
Formulas [1 ′], [2 ′], [3 ′] and [4 ′] A: B = 85: 15 to 15:85 [1 ′] (A + B): C = 90: 10 to 65:35 [ 2 '] (A + B + C): D = 99.9: 0.1 to 95: 5 [3'] (A + B + C + D): E = 65: 35 [4 '] The isosorbide nitrate-containing patch according to claim 1. .
ニル系粘着剤（Ｂ）、可塑化作用成分（Ｃ）、流動化防
止成分（Ｄ）と硝酸イソソルビド（Ｅ）の重量比率が、
下記式［１”］、［２”］、［３”］、および［４”］ Ａ：Ｂ＝８５：１５〜０：１００ ［１”］ （Ａ＋Ｂ）：Ｃ＝８５：１５〜６５：３５ ［２”］ （Ａ＋Ｂ＋Ｃ）：Ｄ＝９９．９：０．１〜９５：５ ［３”］ （Ａ＋Ｂ＋Ｃ＋Ｄ）：Ｅ＝８０：２０〜６５：３５ ［４”］ を満足する請求項１記載の硝酸イソソルビド含有貼付
剤。6. The weight ratio of the silicone adhesive (A), the polyvinyl acetate adhesive (B), the plasticizing component (C), the fluidization preventing component (D) and the isosorbide dinitrate (E) is
Formulas [1 ″], [2 ″], [3 ″], and [4 ″] A: B = 85: 15 to 0: 100 [1 ″] (A + B): C = 85: 15 to 65:35 [2 ″] (A + B + C): D = 99.9: 0.1 to 95: 5 [3 ″] (A + B + C + D): E = 80: 20 to 65:35 [4 ″] A patch containing isosorbide dinitrate.
以上の飽和若しくは不飽和の脂肪酸、そのエステル類、
α−トコフェロール、およびその誘導体からなる群から
選ばれる１種又は２種以上である請求項１〜６のいずれ
か１項に記載の硝酸イソソルビド含有貼付剤。7. The plasticizing component (C) has 12 carbon atoms.
The above saturated or unsaturated fatty acids, their esters,
The isosorbide dinitrate-containing patch according to any one of claims 1 to 6, which is one or more selected from the group consisting of α-tocopherol and its derivatives.
［Ｉ］ 【化１】 で示される粘着剤である請求項１〜６のいずれか１項に
記載の硝酸イソソルビド含有貼付剤。8. The silicone-based pressure-sensitive adhesive (A) is represented by the following formula [I]: The isosorbide dinitrate-containing patch according to any one of claims 1 to 6, which is an adhesive represented by.
ピロリドン、２〜３価の金属の有機金属塩および金属キ
レート化合物からなる群より選ばれる１種又は２種以上
である請求項１〜６のいずれか１項に記載の硝酸イソソ
ルビド含有貼付剤。9. The fluidization preventing component (D) is one or more selected from the group consisting of polyvinylpyrrolidone, organometallic salts of divalent to trivalent metals and metal chelate compounds. 7. The isosorbide dinitrate-containing patch according to any one of 6 above.
酢酸ビニルと平均炭素数３〜１４のアルキル基からなる
（メタ）アクリル酸アルキルエステルおよび／又は（メ
タ）アクリル酸との共重合ポリマーであって、少なくと
も該酢酸ビニルの共重合比率が５０重量％以上である請
求項１〜６のいずれか１項に記載の硝酸イソソルビド含
有貼付剤。10. The polyvinyl acetate-based pressure-sensitive adhesive (B) comprises:
A copolymer of vinyl acetate and a (meth) acrylic acid alkyl ester having an average number of carbon atoms of 3 to 14 and / or (meth) acrylic acid, wherein the copolymerization ratio of at least the vinyl acetate is 50% by weight. The above is the patch containing isosorbide nitrate according to any one of claims 1 to 6.
酢酸ビニルと２−エチルヘキシル（メタ）アクリレート
および／又は（メタ）アクリル酸成分の共重合比率が６
０：４０〜８０：２０で、ポリスチレン換算での重量平
均分子量が１５０，０００〜８００，０００の粘着剤で
ある請求項１〜６のいずれか１項に記載の硝酸イソソル
ビド含有貼付剤。11. The polyvinyl acetate adhesive (B) comprises:
The copolymerization ratio of vinyl acetate and 2-ethylhexyl (meth) acrylate and / or (meth) acrylic acid component is 6
The isosorbide dinitrate-containing patch according to any one of claims 1 to 6, which is an adhesive having a weight average molecular weight of 150,000 to 800,000 in terms of polystyrene at 0:40 to 80:20.
４．９μｍのポリエステルフィルム、（ｂ）厚み５〜４
０μｍの接着剤層、（ｃ）目付け８〜３０ｇ／ｍ2 のポ
リエステル布帛、（ｄ）厚み５〜４０μｍの接着剤層、
（ｅ）厚み０．５〜４．９μｍのポリエステルフィルム
をこの順番で積層したもの、又はこれら（ａ）ないし
（ｅ）から（ｂ）又は（ｄ）の１層を除いて積層したも
のであって、かつ該（ｅ）の自由になっている面に該粘
着性組成物が積層せしめられるものである、請求項１記
載の硝酸イソソルビド含有貼付剤。12. The flexible carrier has (a) a thickness of 0.5 to
4.9 μm polyester film, (b) thickness 5-4
0 μm adhesive layer, (c) basis weight 8-30 g / m 2 polyester cloth, (d) thickness 5-40 μm adhesive layer,
(E) A laminate of polyester films having a thickness of 0.5 to 4.9 μm in this order, or a laminate of these (a) to (e) except for one layer of (b) or (d). The adhesive patch containing isosorbide nitrate according to claim 1, wherein the adhesive composition is laminated on the free surface of (e).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP21052095A JPH0959152A (en) | 1995-08-18 | 1995-08-18 | Isosorbide dinitrate-containing plaster |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP21052095A JPH0959152A (en) | 1995-08-18 | 1995-08-18 | Isosorbide dinitrate-containing plaster |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0959152A true JPH0959152A (en) | 1997-03-04 |
Family
ID=16590735
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP21052095A Pending JPH0959152A (en) | 1995-08-18 | 1995-08-18 | Isosorbide dinitrate-containing plaster |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0959152A (en) |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001345200A (en) * | 2000-05-31 | 2001-12-14 | Ebara Corp | Method of manufacturing charged particle accelerating tube |
| EP1244455A1 (en) * | 1999-10-29 | 2002-10-02 | Nitromed, Inc. | Methods of treating vascular diseases characterized by nitric oxide insufficiency |
| WO2006051819A1 (en) * | 2004-11-10 | 2006-05-18 | Hisamitsu Pharmaceutical Co., Inc. | Drug for external use and adhesive patch |
| US7235237B2 (en) | 1999-10-29 | 2007-06-26 | Nitromed, Inc. | Methods of treating vascular diseases characterized by nitric oxide insufficiency |
| US7537785B2 (en) | 1999-10-29 | 2009-05-26 | Nitromed, Inc. | Composition for treating vascular diseases characterized by nitric oxide insufficiency |
| JP2009144164A (en) * | 1998-03-14 | 2009-07-02 | Lts Lohmann Therapie-Systeme Ag | Silicone contact adhesive with reduced cold flow |
| US7708989B2 (en) | 1999-10-29 | 2010-05-04 | Nitromed, Inc. | Methods of treating vascular diseases characterized by nitric oxide insufficiency |
| US7951397B2 (en) | 2002-02-20 | 2011-05-31 | Nycomed Gmbh | Oral dosage form containing a PDE 4 inhibitor as an active ingredient and polyvinylpyrrolidon as excipient |
| US7951398B2 (en) | 2000-12-07 | 2011-05-31 | Nycomed Gmbh | Pharmaceutical preparation comprising an active dispersed on a matrix |
| JP2013087289A (en) * | 2011-10-21 | 2013-05-13 | Dow Corning Corp | Single phase silicone acrylate formulation |
-
1995
- 1995-08-18 JP JP21052095A patent/JPH0959152A/en active Pending
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009144164A (en) * | 1998-03-14 | 2009-07-02 | Lts Lohmann Therapie-Systeme Ag | Silicone contact adhesive with reduced cold flow |
| EP1244455A1 (en) * | 1999-10-29 | 2002-10-02 | Nitromed, Inc. | Methods of treating vascular diseases characterized by nitric oxide insufficiency |
| US7235237B2 (en) | 1999-10-29 | 2007-06-26 | Nitromed, Inc. | Methods of treating vascular diseases characterized by nitric oxide insufficiency |
| US7537785B2 (en) | 1999-10-29 | 2009-05-26 | Nitromed, Inc. | Composition for treating vascular diseases characterized by nitric oxide insufficiency |
| US7556824B2 (en) | 1999-10-29 | 2009-07-07 | Nitromed, Inc. | Transdermal patch composition for treating vascular diseases characterized by nitric oxide insufficiency |
| US7708989B2 (en) | 1999-10-29 | 2010-05-04 | Nitromed, Inc. | Methods of treating vascular diseases characterized by nitric oxide insufficiency |
| JP2001345200A (en) * | 2000-05-31 | 2001-12-14 | Ebara Corp | Method of manufacturing charged particle accelerating tube |
| US7951398B2 (en) | 2000-12-07 | 2011-05-31 | Nycomed Gmbh | Pharmaceutical preparation comprising an active dispersed on a matrix |
| US7951397B2 (en) | 2002-02-20 | 2011-05-31 | Nycomed Gmbh | Oral dosage form containing a PDE 4 inhibitor as an active ingredient and polyvinylpyrrolidon as excipient |
| US8431154B2 (en) | 2002-02-20 | 2013-04-30 | Takeda Gmbh | Oral dosage form containing a PDE 4 inhibitor as an active ingredient and polyvinylpyrrolidone as excipient |
| WO2006051819A1 (en) * | 2004-11-10 | 2006-05-18 | Hisamitsu Pharmaceutical Co., Inc. | Drug for external use and adhesive patch |
| JP2013087289A (en) * | 2011-10-21 | 2013-05-13 | Dow Corning Corp | Single phase silicone acrylate formulation |
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