JPS63307814A - Patch for treating diseases - Google Patents
Patch for treating diseasesInfo
- Publication number
- JPS63307814A JPS63307814A JP14264087A JP14264087A JPS63307814A JP S63307814 A JPS63307814 A JP S63307814A JP 14264087 A JP14264087 A JP 14264087A JP 14264087 A JP14264087 A JP 14264087A JP S63307814 A JPS63307814 A JP S63307814A
- Authority
- JP
- Japan
- Prior art keywords
- drug
- patch
- meth
- adhesive layer
- carboxyl group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 201000010099 disease Diseases 0.000 title claims description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims description 21
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 40
- 229920001577 copolymer Polymers 0.000 claims abstract description 22
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 claims abstract description 11
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 6
- 239000005557 antagonist Substances 0.000 claims abstract description 6
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 claims abstract description 3
- 229940079593 drug Drugs 0.000 claims description 116
- 239000003814 drug Substances 0.000 claims description 116
- 239000010410 layer Substances 0.000 claims description 58
- 239000003522 acrylic cement Substances 0.000 claims description 29
- 239000012790 adhesive layer Substances 0.000 claims description 21
- 239000002861 polymer material Substances 0.000 claims description 20
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 claims description 2
- 239000000126 substance Substances 0.000 abstract description 19
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 abstract description 17
- 229920000642 polymer Polymers 0.000 abstract description 14
- 238000010521 absorption reaction Methods 0.000 abstract description 10
- 230000000694 effects Effects 0.000 abstract description 10
- 229920000058 polyacrylate Polymers 0.000 abstract description 6
- 230000037374 absorbed through the skin Effects 0.000 abstract description 3
- 230000009477 glass transition Effects 0.000 abstract description 2
- 239000004480 active ingredient Substances 0.000 abstract 7
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 abstract 1
- 239000011248 coating agent Substances 0.000 abstract 1
- 238000000576 coating method Methods 0.000 abstract 1
- -1 polyethylene Polymers 0.000 description 29
- 210000003491 skin Anatomy 0.000 description 26
- 239000000178 monomer Substances 0.000 description 20
- 230000000052 comparative effect Effects 0.000 description 10
- 238000006116 polymerization reaction Methods 0.000 description 8
- 229910052782 aluminium Inorganic materials 0.000 description 7
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 7
- 238000001035 drying Methods 0.000 description 7
- 229920001971 elastomer Polymers 0.000 description 7
- 230000000144 pharmacologic effect Effects 0.000 description 7
- 239000005060 rubber Substances 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 108010076876 Keratins Proteins 0.000 description 6
- 102000011782 Keratins Human genes 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 230000001070 adhesive effect Effects 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 239000004698 Polyethylene Substances 0.000 description 5
- 239000004820 Pressure-sensitive adhesive Substances 0.000 description 5
- 239000000853 adhesive Substances 0.000 description 5
- 229920000573 polyethylene Polymers 0.000 description 5
- 230000002459 sustained effect Effects 0.000 description 5
- RSWGJHLUYNHPMX-UHFFFAOYSA-N Abietic-Saeure Natural products C12CCC(C(C)C)=CC2=CCC2C1(C)CCCC2(C)C(O)=O RSWGJHLUYNHPMX-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- RRHGJUQNOFWUDK-UHFFFAOYSA-N Isoprene Chemical compound CC(=C)C=C RRHGJUQNOFWUDK-UHFFFAOYSA-N 0.000 description 4
- KHPCPRHQVVSZAH-HUOMCSJISA-N Rosin Natural products O(C/C=C/c1ccccc1)[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 KHPCPRHQVVSZAH-HUOMCSJISA-N 0.000 description 4
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 4
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 4
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 4
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 4
- KHPCPRHQVVSZAH-UHFFFAOYSA-N trans-cinnamyl beta-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OCC=CC1=CC=CC=C1 KHPCPRHQVVSZAH-UHFFFAOYSA-N 0.000 description 4
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 3
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 229920002367 Polyisobutene Polymers 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000004202 carbamide Substances 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 239000004014 plasticizer Substances 0.000 description 3
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 3
- 229920002554 vinyl polymer Polymers 0.000 description 3
- KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 2
- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 2
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 2
- GOXQRTZXKQZDDN-UHFFFAOYSA-N 2-Ethylhexyl acrylate Chemical compound CCCCC(CC)COC(=O)C=C GOXQRTZXKQZDDN-UHFFFAOYSA-N 0.000 description 2
- 206010002383 Angina Pectoris Diseases 0.000 description 2
- SOGAXMICEFXMKE-UHFFFAOYSA-N Butylmethacrylate Chemical compound CCCCOC(=O)C(C)=C SOGAXMICEFXMKE-UHFFFAOYSA-N 0.000 description 2
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 239000004952 Polyamide Substances 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N Vilsmeier-Haack reagent Natural products CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 2
- 235000019169 all-trans-retinol Nutrition 0.000 description 2
- 239000011717 all-trans-retinol Substances 0.000 description 2
- 229960004022 clotrimazole Drugs 0.000 description 2
- VNFPBHJOKIVQEB-UHFFFAOYSA-N clotrimazole Chemical compound ClC1=CC=CC=C1C(N1C=NC=C1)(C=1C=CC=CC=1)C1=CC=CC=C1 VNFPBHJOKIVQEB-UHFFFAOYSA-N 0.000 description 2
- 238000007334 copolymerization reaction Methods 0.000 description 2
- 238000009792 diffusion process Methods 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- MMXKVMNBHPAILY-UHFFFAOYSA-N ethyl laurate Chemical compound CCCCCCCCCCCC(=O)OCC MMXKVMNBHPAILY-UHFFFAOYSA-N 0.000 description 2
- 150000002334 glycols Chemical class 0.000 description 2
- 229960003878 haloperidol Drugs 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000004745 nonwoven fabric Substances 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- 230000035699 permeability Effects 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
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- 229920002635 polyurethane Polymers 0.000 description 2
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- 239000011148 porous material Substances 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 229960003471 retinol Drugs 0.000 description 2
- 229960004889 salicylic acid Drugs 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 229920001059 synthetic polymer Polymers 0.000 description 2
- 229920003002 synthetic resin Polymers 0.000 description 2
- 239000000057 synthetic resin Substances 0.000 description 2
- DIWRORZWFLOCLC-HNNXBMFYSA-N (3s)-7-chloro-5-(2-chlorophenyl)-3-hydroxy-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound N([C@H](C(NC1=CC=C(Cl)C=C11)=O)O)=C1C1=CC=CC=C1Cl DIWRORZWFLOCLC-HNNXBMFYSA-N 0.000 description 1
- YQSHYGCCYVPRDI-UHFFFAOYSA-N (4-propan-2-ylphenyl)methanamine Chemical compound CC(C)C1=CC=C(CN)C=C1 YQSHYGCCYVPRDI-UHFFFAOYSA-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
- BFUXUGOZJVHVMR-UHFFFAOYSA-N 1,1-dioxo-3,4-dihydro-2h-1$l^{6},2,4-benzothiadiazine-7-sulfonamide Chemical compound N1CNS(=O)(=O)C2=CC(S(=O)(=O)N)=CC=C21 BFUXUGOZJVHVMR-UHFFFAOYSA-N 0.000 description 1
- NJPQAIBZIHNJDO-UHFFFAOYSA-N 1-dodecylpyrrolidin-2-one Chemical compound CCCCCCCCCCCCN1CCCC1=O NJPQAIBZIHNJDO-UHFFFAOYSA-N 0.000 description 1
- OSSNTDFYBPYIEC-UHFFFAOYSA-N 1-ethenylimidazole Chemical compound C=CN1C=CN=C1 OSSNTDFYBPYIEC-UHFFFAOYSA-N 0.000 description 1
- PBGPBHYPCGDFEZ-UHFFFAOYSA-N 1-ethenylpiperidin-2-one Chemical compound C=CN1CCCCC1=O PBGPBHYPCGDFEZ-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- PVVATGNFHKTPTA-UHFFFAOYSA-N 1-methylsulfinyloctane Chemical compound CCCCCCCCS(C)=O PVVATGNFHKTPTA-UHFFFAOYSA-N 0.000 description 1
- BCQOPKZWRYKQCO-UHFFFAOYSA-N 12,12-dimethyltridecan-1-amine Chemical compound CC(C)(C)CCCCCCCCCCCN BCQOPKZWRYKQCO-UHFFFAOYSA-N 0.000 description 1
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- ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 2,3-dimethylbutane Chemical group CC(C)C(C)C ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 0.000 description 1
- JAHNSTQSQJOJLO-UHFFFAOYSA-N 2-(3-fluorophenyl)-1h-imidazole Chemical compound FC1=CC=CC(C=2NC=CN=2)=C1 JAHNSTQSQJOJLO-UHFFFAOYSA-N 0.000 description 1
- PGMMQIGGQSIEGH-UHFFFAOYSA-N 2-ethenyl-1,3-oxazole Chemical compound C=CC1=NC=CO1 PGMMQIGGQSIEGH-UHFFFAOYSA-N 0.000 description 1
- ZDHWTWWXCXEGIC-UHFFFAOYSA-N 2-ethenylpyrimidine Chemical compound C=CC1=NC=CC=N1 ZDHWTWWXCXEGIC-UHFFFAOYSA-N 0.000 description 1
- FWWXYLGCHHIKNY-UHFFFAOYSA-N 2-ethoxyethyl prop-2-enoate Chemical compound CCOCCOC(=O)C=C FWWXYLGCHHIKNY-UHFFFAOYSA-N 0.000 description 1
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- AGBXYHCHUYARJY-UHFFFAOYSA-N 2-phenylethenesulfonic acid Chemical compound OS(=O)(=O)C=CC1=CC=CC=C1 AGBXYHCHUYARJY-UHFFFAOYSA-N 0.000 description 1
- YVGWMNRYRLGBNQ-UHFFFAOYSA-N 2-prop-2-enoyloxybenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1OC(=O)C=C YVGWMNRYRLGBNQ-UHFFFAOYSA-N 0.000 description 1
- MEAPRSDUXBHXGD-UHFFFAOYSA-N 3-chloro-n-(4-propan-2-ylphenyl)propanamide Chemical compound CC(C)C1=CC=C(NC(=O)CCCl)C=C1 MEAPRSDUXBHXGD-UHFFFAOYSA-N 0.000 description 1
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- UIAGMCDKSXEBJQ-IBGZPJMESA-N 3-o-(2-methoxyethyl) 5-o-propan-2-yl (4s)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COCCOC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)[C@H]1C1=CC=CC([N+]([O-])=O)=C1 UIAGMCDKSXEBJQ-IBGZPJMESA-N 0.000 description 1
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- CFZDMXAOSDDDRT-UHFFFAOYSA-N 4-ethenylmorpholine Chemical compound C=CN1CCOCC1 CFZDMXAOSDDDRT-UHFFFAOYSA-N 0.000 description 1
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- PJJGZPJJTHBVMX-UHFFFAOYSA-N 5,7-Dihydroxyisoflavone Chemical compound C=1C(O)=CC(O)=C(C2=O)C=1OC=C2C1=CC=CC=C1 PJJGZPJJTHBVMX-UHFFFAOYSA-N 0.000 description 1
- DXPPIEDUBFUSEZ-UHFFFAOYSA-N 6-methylheptyl prop-2-enoate Chemical compound CC(C)CCCCCOC(=O)C=C DXPPIEDUBFUSEZ-UHFFFAOYSA-N 0.000 description 1
- CUXGDKOCSSIRKK-UHFFFAOYSA-N 7-methyloctyl prop-2-enoate Chemical compound CC(C)CCCCCCOC(=O)C=C CUXGDKOCSSIRKK-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- QWOJMRHUQHTCJG-UHFFFAOYSA-N CC([CH2-])=O Chemical compound CC([CH2-])=O QWOJMRHUQHTCJG-UHFFFAOYSA-N 0.000 description 1
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- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical group CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 1
- 239000004129 EU approved improving agent Substances 0.000 description 1
- BALXUFOVQVENIU-GNAZCLTHSA-N Ephedrine hydrochloride Chemical compound Cl.CN[C@@H](C)[C@H](O)C1=CC=CC=C1 BALXUFOVQVENIU-GNAZCLTHSA-N 0.000 description 1
- UUOUOERPONYGOS-CLCRDYEYSA-N Fluocinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3C[C@H](F)C2=C1 UUOUOERPONYGOS-CLCRDYEYSA-N 0.000 description 1
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- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 239000005033 polyvinylidene chloride Substances 0.000 description 1
- 229960005205 prednisolone Drugs 0.000 description 1
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- UIIIBRHUICCMAI-UHFFFAOYSA-N prop-2-ene-1-sulfonic acid Chemical compound OS(=O)(=O)CC=C UIIIBRHUICCMAI-UHFFFAOYSA-N 0.000 description 1
- 229960003712 propranolol Drugs 0.000 description 1
- 229960004604 propranolol hydrochloride Drugs 0.000 description 1
- JNTOKFNBDFMTIV-UHFFFAOYSA-N propyl nitrate Chemical compound CCCO[N+]([O-])=O JNTOKFNBDFMTIV-UHFFFAOYSA-N 0.000 description 1
- 238000009790 rate-determining step (RDS) Methods 0.000 description 1
- 229940116351 sebacate Drugs 0.000 description 1
- CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 229920002379 silicone rubber Polymers 0.000 description 1
- 239000004945 silicone rubber Substances 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 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
- 238000003756 stirring Methods 0.000 description 1
- 210000000434 stratum corneum Anatomy 0.000 description 1
- 229920006132 styrene block copolymer Polymers 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 229960002673 sulfacetamide Drugs 0.000 description 1
- SKIVFJLNDNKQPD-UHFFFAOYSA-N sulfacetamide Chemical compound CC(=O)NS(=O)(=O)C1=CC=C(N)C=C1 SKIVFJLNDNKQPD-UHFFFAOYSA-N 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 125000004962 sulfoxyl group Chemical group 0.000 description 1
- 229960000894 sulindac Drugs 0.000 description 1
- MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 description 1
- 238000013269 sustained drug release Methods 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- IWVCMVBTMGNXQD-UHFFFAOYSA-N terramycin dehydrate Natural products C1=CC=C2C(O)(C)C3C(O)C4C(N(C)C)C(O)=C(C(N)=O)C(=O)C4(O)C(O)=C3C(=O)C2=C1O IWVCMVBTMGNXQD-UHFFFAOYSA-N 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 229960002044 tolmetin sodium Drugs 0.000 description 1
- 239000003204 tranquilizing agent Substances 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
- 125000002889 tridecyl 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])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- RRLMGCBZYFFRED-UHFFFAOYSA-N undecyl prop-2-enoate Chemical compound CCCCCCCCCCCOC(=O)C=C RRLMGCBZYFFRED-UHFFFAOYSA-N 0.000 description 1
- 150000003673 urethanes Chemical class 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 235000001892 vitamin D2 Nutrition 0.000 description 1
- 239000011653 vitamin D2 Substances 0.000 description 1
- MECHNRXZTMCUDQ-RKHKHRCZSA-N vitamin D2 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)/C=C/[C@H](C)C(C)C)=C\C=C1\C[C@@H](O)CCC1=C MECHNRXZTMCUDQ-RKHKHRCZSA-N 0.000 description 1
- 235000005282 vitamin D3 Nutrition 0.000 description 1
- 239000011647 vitamin D3 Substances 0.000 description 1
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 1
- 229940021056 vitamin d3 Drugs 0.000 description 1
- 239000002759 woven fabric Substances 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
Description
【発明の詳細な説明】
（、）産業上の利用分野
本発明は経皮的に薬物を生体内へ投与するための疾患治
療用貼付剤に関する。DETAILED DESCRIPTION OF THE INVENTION Field of the Invention The present invention relates to a disease-treating patch for transdermally administering a drug into a living body.
（ｂ）従来の技術
近年、薬物を生体内へ投与する手段として皮膚面を通し
て投与する経皮吸収法が、持続的な薬理効果の発現や副
作用の軽減などの点から盛んに開発されており、その中
でも粘着テープ状に製剤化された貼付剤が取り扱いの簡
便さや投薬量の厳格さの点から注目されている。(b) Prior art In recent years, transdermal absorption methods, in which drugs are administered through the skin, have been actively developed as a means of administering drugs into living bodies, from the viewpoint of producing sustained pharmacological effects and reducing side effects. Among these, patches formulated in the form of adhesive tapes are attracting attention because of their ease of handling and strict dosage requirements.
このような貼付剤の基本構造は、プラスチックフィルム
や不織布などからなる支持体と、該支持体の片面に設け
られた薬物含有層からなるものであり、薬物含有層に種
々の工夫を施して速効性や持続性、その他の作用を発揮
させようとするものである。The basic structure of such patches consists of a support made of plastic film or nonwoven fabric, and a drug-containing layer provided on one side of the support. It is an attempt to exert properties such as durability, sustainability, and other effects.
例えば特公昭５４−１６５６６号公報には含有する薬物
の放出をコントロールするために、薬物含有層を薬物貯
蔵層、薬物放出コンドロール膜、粘着剤層の３Ｎからな
る積層構造として貼付剤や、薬物を内包した薬物放出コ
ントロール性のマイクロカプセルを粘着剤層に分散させ
た貼付剤が開示されている。For example, in Japanese Patent Publication No. 54-16566, in order to control the release of the drug contained in it, the drug-containing layer is made into a 3N layered structure consisting of a drug storage layer, a drug-releasing chondrol film, and an adhesive layer. A patch is disclosed in which microcapsules containing drug release control properties are dispersed in an adhesive layer.
また、特公昭６０−５５０４４号公報にも薬物の放出性
をコントロールするために、薬物貯蔵層と粘着剤層との
積層構造で、かっ該両層内での薬物の拡散係数や溶解度
などを特定の範囲に設定した貼付剤が開示されている。In addition, Japanese Patent Publication No. 60-55044 also states that in order to control drug release, a laminated structure of a drug storage layer and an adhesive layer is used to determine the diffusion coefficient and solubility of the drug within both layers. A patch set within the range of is disclosed.
（ｅ）発明が解決しようとする問題点
上記貼付剤の特徴は長期間にわたって薬理効果を持続さ
せようとすることにあるが、前者の貼付剤では薬物放出
コントロール膜やマイクロカプセルの壁を薬物が通過す
る過程が律速段階となるために、僅かの欠損部が存在す
るとコントロールができなくなったり、またその厳格な
制御性のために薬物貯蔵層中の薬物総てが有効に放出さ
れない場合もある。(e) Problems to be solved by the invention The characteristics of the above-mentioned patches are that they attempt to maintain pharmacological effects over a long period of time. Since the passing process is the rate-determining step, the presence of a small defect may result in loss of control, and due to the strict controllability, not all of the drug in the drug storage layer may be effectively released.
また、後者の貼付剤では薬物が貯蔵層からスムースに粘
着剤層に移行し、その後移行した薬物が粘着剤層から良
好に皮膚面に放出されることもあるが、皮膚面への薬物
の放出に対して重要な役割を果たす粘着剤層については
何ら検討されておらず、皮膚面への薬物の放出が確実に
起こるとはいい難いものである。In addition, in the latter patch, the drug may smoothly transfer from the storage layer to the adhesive layer, and then the transferred drug may be released from the adhesive layer to the skin surface. No consideration has been given to the adhesive layer, which plays an important role in the release of drugs to the skin surface.
一方、近年になって狭心症や高血圧症の症状を訴える患
者数は年々増加の一途をたどっており、これらの症状を
予防改善するような優れた持続的薬理効果を発揮する製
剤が切望されているにも拘わらず、未だ充分なものが開
発、提供されていないのが実状である。On the other hand, in recent years, the number of patients complaining of symptoms of angina pectoris and hypertension has been increasing year by year, and there is a strong need for preparations that exhibit excellent and sustained pharmacological effects to prevent and improve these symptoms. However, the reality is that sufficient products have not yet been developed or provided.
（ｄ）問題点を解決するための手段
本発明者らは上記問題点に鑑み、持続的な薬理効果を示
し、且つ皮膚面を通しで生体内への薬物の移行性が良好
な貼付剤を提供すべく検討を重ねた結果、カルボキシル
基を含有するアクリル系粘着剤は薬物の溶解性が若干劣
る反面、薬物の放出性並びに生体内への移行性において
極めて優れた効果を発揮することを見い出し、本発明を
完成するに至ったものである。(d) Means for Solving the Problems In view of the above problems, the present inventors have developed a patch that exhibits a sustained pharmacological effect and has good drug transferability into the body through the skin surface. As a result of repeated studies, we discovered that although acrylic adhesives containing carboxyl groups have slightly poor drug solubility, they are extremely effective in terms of drug release and in vivo migration. , which led to the completion of the present invention.
即ち、本発明の疾患治療用貼付剤は、支持体の片面に薬
物含有高分子物質層及びカルボキシル基含有アクリル系
粘着剤層を順次積層してなる貼付剤であって、上記粘着
剤層は実質的に薬物を含有しないか、もしくは薬物含有
高分子物質層よりも低濃度にて薬物を含有してなるもの
である。That is, the patch for disease treatment of the present invention is a patch comprising a drug-containing polymer material layer and a carboxyl group-containing acrylic adhesive layer sequentially laminated on one side of a support, and the adhesive layer is substantially Either it does not contain a drug, or it contains a drug at a lower concentration than the drug-containing polymer material layer.
以下、本発明の詳細な説明する。The present invention will be explained in detail below.
本発明の疾患治療用貼付剤に用いられる支持体としては
、従来から使用されている支持体、例えばポリエチレン
、ポリプロピレン、ポリエステル、ポリ酢酸ビニル、ポ
リウレタン、ポリビニルアルコール、ポリ塩化ビニリデ
ン、ポリアミドなどの材料からなる単層フィルムや単層
シート、ゴム及び／又は合成樹脂製発泡フィルムやシー
ト、不織布、織布、金属箔或いはこれらで形成された積
層フィルムや積層シート等が使用でき、これらの支持体
は目的に応じて穿孔処理を施して使用することもできる
。The support used in the patch for disease treatment of the present invention may be selected from conventionally used supports such as polyethylene, polypropylene, polyester, polyvinyl acetate, polyurethane, polyvinyl alcohol, polyvinylidene chloride, polyamide, etc. Single-layer films and sheets made of rubber and/or synthetic resin, foamed films and sheets made of rubber and/or synthetic resin, non-woven fabrics, woven fabrics, metal foils, and laminated films and sheets made of these can be used. It can also be used with perforation treatment depending on the situation.
上記支持体の片面に設けられろ薬物含有高分子物質層は
、経皮吸収性の薬物の溶解性が良好であり、しかも、該
薬物を含有、保持し、本発明の疾患治療用貼付剤に持続
的な薬物の放出性を付与する作用を示す層である。The drug-containing polymer material layer provided on one side of the support has good solubility for transdermally absorbable drugs, contains and retains the drug, and is suitable for use in the patch for treating diseases of the present invention. This layer has the effect of providing sustained drug release.
即ち、後述のカルボキシル基含有アクリル系粘着剤層か
ら皮膚面に薬物が放出、移行することによって当該粘着
剤層中の薬物濃度が低下すると、減少した量の薬物を補
うように濃度差によって薬物含有高分子物１１１層から
薬物を粘着剤層中へ移行、補給して薬物の持続的放出を
発揮するのである。That is, when the drug concentration in the adhesive layer decreases due to release and transfer of the drug from the carboxyl group-containing acrylic adhesive layer described below to the skin surface, the concentration difference causes the drug content to compensate for the decreased amount of drug. The drug is transferred from the polymer 111 layer into the adhesive layer and replenished to achieve sustained release of the drug.
このような高分子物質層を形成するものとしては、合成
高分子物質、半合成高分子物質、天然高分子物質を問わ
ず使用することができるが、隣接する支持体及びカルボ
キシル基含有アクリル系粘着剤層との親和性、投錨性、
接着性を考慮すると粘着性の高分子物質を用いることが
好ましく、特にカルボキシル基含有アクリル系粘着剤層
との親和性の点からアクリル系高分子物質を用いること
が望ましい。As for forming such a polymer material layer, synthetic polymer materials, semi-synthetic polymer materials, and natural polymer materials can be used, but the adjoining support and carboxyl group-containing acrylic adhesive can be used. affinity with the agent layer, anchoring ability,
In consideration of adhesive properties, it is preferable to use a sticky polymeric substance, and in particular, it is desirable to use an acrylic polymeric substance from the viewpoint of affinity with the carboxyl group-containing acrylic adhesive layer.
そして、上記アクリル系高分子物質のうち好ましいもの
は、そのガラス転移温度（Ｔｇ）が−７０〜−１０℃の
ものであり、Ｔｇが−５５〜−２５℃のものが更に好ま
しい。Among the above acrylic polymer substances, those having a glass transition temperature (Tg) of -70 to -10°C are preferable, and those having a Tg of -55 to -25°C are more preferable.
Ｔｇが上記範囲の場合には、基材の保形性、アクリル系
高分子物質中での薬物の拡散移動性が優れ、従って薬物
の放出性が良好となる。When Tg is within the above range, the shape retention of the base material and the diffusion mobility of the drug in the acrylic polymer material are excellent, and therefore the drug release properties are excellent.
尚、上記アクリル系高分子物質に流動パラフィンの如き
相溶性のよい液状の軟化成分や、各種軟化剤などの一般
に知られる配合剤を添加してＴｇを調整することも任意
である。It is also optional to adjust the Tg by adding generally known compounding agents such as a liquid softening component with good compatibility such as liquid paraffin or various softeners to the above-mentioned acrylic polymer material.
上記アクリル系高分子物質としては、例えばアルキル基
の炭素数が４以上の（メタ）アクリル酸アルキルエステ
ルの単独重合体、或いは（７り）７クリル酸アルキルエ
ステルを主成分単量体として共重合して得られる共重合
体を挙げることができる。The above-mentioned acrylic polymer material is, for example, a homopolymer of (meth)acrylic acid alkyl ester in which the alkyl group has 4 or more carbon atoms, or a copolymer with (7)7-acrylic acid alkyl ester as the main monomer. Examples include copolymers obtained by
上記（メタ）アクリル酸アルキルエステルとしては、例
えばｎ−ブチル７クリレー）、ｎ−ブチルメタクリレー
ト、ヘキシルアクリレート、２−エチルブチルアクリレ
ート、インオクチル７クリレート、２−エチルへキシル
アクリレート、２−エチルへキシルメタクリレート、ウ
ンデシルアクリレート、ドデシルアクリレート、トリデ
シルアクリレ−１，Ｙリゾシルメタクリレートなどを挙
げることができる。Examples of the (meth)acrylic acid alkyl esters include n-butyl 7-acrylate, n-butyl methacrylate, hexyl acrylate, 2-ethyl butyl acrylate, inoctyl 7-acrylate, 2-ethylhexyl acrylate, and 2-ethylhexyl. Examples include methacrylate, undecyl acrylate, dodecyl acrylate, tridecyl acrylate-1, Y-lysosyl methacrylate, and the like.
又、上記（メタ）アクリル酸アルキルエステルと共重合
する他の単量体としては、例えば（メタ）アクリル酸、
イタコン酸、マレイン酸、無水マレイン酸、７マール酸
の如塾カルボキシル基含有単量体、スチレンスルホン酸
、アリルスルホン酸、スルホプロピルアクリレート、（
メタ）アクリロイルオキシナフタレンスルホン酸、アク
リルアミドメチルプロパンスルホン酸、アクリロイ°ル
オキシベンゼンスルホン酸の如きスルホキシル基含有単
量体、（メタ）アクリル酸ヒドロキシエチルエステル、
（メタ）アクリル酸ヒドロキシプロピルエステルの如き
ヒドロキシル基含有単量体、（メタ）アクリルアミド、
ツメチル（メタ）アクリルアミド、Ｎ−ブチルアクリル
アミド、テトラメチルブチルアクリルアミド、Ｎ−メチ
ロール（メタ）アクリルアミドの如きアミド基含有アク
リル系単量体、（メタ）アクリル酸アミノエチルエステ
ル、（メタ）アクリル酸ジメチルアミノエチルエステル
、（メタ）アクリル酸ジエチル７ミ／エチルエステル、
（メタ）アクリルｆｉｌｔｅｒｔ−ブチルアミノエチル
エステルの如きアルキルアミノアルえル基含有アクリル
系単量体、（メタ）アクリル酸メトキシエチルエステル
、（メタ）アクリル酸エトキシエチルエステル、（メタ
）アクリル酸ブトキシエチルエステル等の（メタ）アク
リル酸アルコキシアルキルエステル、（メタ）アクリル
酸テトラヒドロフルフリルエステル、（ツタ）アクリル
酸メトキシエチレングリコールエステル、（メタ）７ク
リル酸メトキシジエチレングリコールエステル、（メタ
）アクリル酸メトキシポリエチレングリコールエステル
、（メタ）アクリル酸メＹキシポリプロピレングリコー
ルエステルの如きアルコキシ基（又は側鎖にエーテル結
合）含有単量体、Ｎ−（メタ）アクリロイルアミノ酸の
如きビニル系単量体、アクリル酸のウレタン、尿素、イ
ソシアネートエステルの如きアクリル系単量体などの官
能性単量体、及び（メタ）７クリロニトリル、酢酸ビニ
ル、プロピオン酸ビニル、ビニルピロリドン、ビニルピ
リノン、ビニルピラノン、ビニルビペラノン、ビニルピ
ペリドン、ビニルピリミジン、ビニルビロール、ビニル
イミダゾール、ビニルカプロラクタム、ビニルオキサゾ
ール、ビニルエアゾール、ビニルモルホリン、スチレン
、ａ−メチルスチレン、ビス（Ｎ、Ｎ″−ツメチルアミ
ノエチル）マレニートなどのビニル系単量体が挙げられ
る。Further, other monomers copolymerized with the above (meth)acrylic acid alkyl ester include (meth)acrylic acid,
Itaconic acid, maleic acid, maleic anhydride, carboxyl group-containing monomer of 7-maric acid, styrene sulfonic acid, allyl sulfonic acid, sulfopropyl acrylate, (
Sulfoxyl group-containing monomers such as meth)acryloyloxynaphthalenesulfonic acid, acrylamide methylpropanesulfonic acid, acryloyloxybenzenesulfonic acid, (meth)acrylic acid hydroxyethyl ester,
Hydroxyl group-containing monomers such as (meth)acrylic acid hydroxypropyl ester, (meth)acrylamide,
Amide group-containing acrylic monomers such as trimethyl(meth)acrylamide, N-butylacrylamide, tetramethylbutylacrylamide, N-methylol(meth)acrylamide, (meth)acrylic acid aminoethyl ester, (meth)acrylic acid dimethylamino Ethyl ester, diethyl (meth)acrylate 7/ethyl ester,
Alkylaminoalyl group-containing acrylic monomers such as (meth)acrylic filtert-butylaminoethyl ester, (meth)acrylic acid methoxyethyl ester, (meth)acrylic acid ethoxyethyl ester, butoxyethyl (meth)acrylate (meth)acrylic acid alkoxyalkyl ester such as ester, (meth)acrylic acid tetrahydrofurfuryl ester, (ivy)acrylic acid methoxyethylene glycol ester, (meth)7acrylic acid methoxydiethylene glycol ester, (meth)acrylic acid methoxypolyethylene glycol ester esters, monomers containing alkoxy groups (or ether bonds in side chains) such as (meth)acrylic acid meyxy-polypropylene glycol esters, vinyl monomers such as N-(meth)acryloyl amino acids, urethanes of acrylic acid, Functional monomers such as urea, acrylic monomers such as isocyanate esters, and (meth)7crylonitrile, vinyl acetate, vinyl propionate, vinylpyrrolidone, vinylpyrinone, vinylpyranone, vinylbiperanone, vinylpiperidone, vinylpyrimidine, vinylvirol, Examples include vinyl monomers such as vinyl imidazole, vinyl caprolactam, vinyl oxazole, vinyl aerosol, vinyl morpholine, styrene, a-methylstyrene, and bis(N,N''-tumethylaminoethyl) maleate.
これらの単量体は主成分単量体との共重合によって凝集
力を付与したり、薬物溶解性を向上させたりする作用を
するものであり、薬物の溶解性が極度に低下しないかぎ
り、共重合比率を任意に選択して用いることができる。These monomers have the effect of imparting cohesive force and improving drug solubility through copolymerization with the main component monomer, and unless the solubility of the drug is extremely reduced, they will not copolymerize. The polymerization ratio can be arbitrarily selected and used.
本発明において、上記（メタ）アクリル酸アルキルエス
テル及び共重合可能な単量体は、アルキル部分が直鎖状
及び分岐状の各種異性体、並びに置換基の位置が異なっ
た各種異性体及び誘導体も包含するものである。In the present invention, the (meth)acrylic acid alkyl ester and the copolymerizable monomer include various isomers in which the alkyl moiety is linear and branched, as well as various isomers and derivatives in which the position of the substituent group is different. It is inclusive.
又、本発明に用いられる池の高分子物質としては、例え
ばシリコーンゴム、ポリイソプレンゴム、ポリイソブチ
レンゴム、ポリブタノエン、スチレ＞−ブ９ジエン（又
はイソプレン）−スチレンブロック共重合体ゴム、アク
リル系ゴム、アラビアゴム等の天然ゴムの如きゴム系物
質、ポリウレタン、ポリエステル、ポリアミド、エチレ
ン−酢酸ビニル共重合体などの合成ｕ１脂などを例示で
きるが、これらの粘着性付与成分としてはロジン及び変
性ロジン、石油系樹脂、ポリテルペン樹脂、ポリスチレ
ン樹脂、ポリブテン、液状ポリイソブチレンが挙げられ
るのであり、また、可塑剤としてはマシン油、トランス
油、ロジン油、各種の流動パラフィンなどが挙げられる
。Further, examples of the polymeric substances used in the present invention include silicone rubber, polyisoprene rubber, polyisobutylene rubber, polybutanoene, styrene>-butylene (or isoprene)-styrene block copolymer rubber, and acrylic rubber. , rubber-based substances such as natural rubber such as gum arabic, synthetic U1 fats such as polyurethane, polyester, polyamide, and ethylene-vinyl acetate copolymer. Examples of these tackifying components include rosin and modified rosin, Examples include petroleum resins, polyterpene resins, polystyrene resins, polybutene, and liquid polyisobutylene. Examples of plasticizers include machine oil, transformer oil, rosin oil, and various liquid paraffins.
更に、他の高分子物質としてはデンプン、変性デンプン
、可溶性デンプン、デキストリン、アルギン酸ナトリウ
ム、カゼイン、ゼラチン等が挙げられる。Further, other polymeric substances include starch, modified starch, soluble starch, dextrin, sodium alginate, casein, gelatin, and the like.
上記高分子物質には薬物が含有されるが、該薬物として
は経皮吸収性のものであれば特に限定されるものではな
く、具体例として以下のものが挙げられる。The above-mentioned polymer substance contains a drug, but the drug is not particularly limited as long as it is transdermally absorbable, and specific examples include the following.
イ）Ｃａ” 拮ＦＣ薬：二７エジピン、ニゾルノビン、
ニモジピン、ニルノビン、ニカルジピン、インロンピン
の如きノヒドロビリンン系Ｃａｚ＋拮抗薬など、口）フ
ルチフステロイド類：例えばハイドロコーチシン、プレ
ドニゾロン、ベクロメタゾンプロピオネート、フルメタ
シン、トリアムシ／ロン、トリアムシ／ロンアセトニド
、フルオシノロン、７ルオシノロンアセトニド、フルオ
シノロンアセトニドアセテート、プロピオン酸クロベタ
ゾールなど、
ノ（）鎮痛消炎剤：例えばアセトアミノ７エン、メフェ
ナム酸、フルフェナム酸、インドメタシン、ジクロ７エ
ナツク、シクロ７エナックナトリウム、アルクロ７エナ
ツク、オキシ７エンプタゾン、７エ二ルフタソン、イブ
フロ７エン、フルルビプロ７エン、サリチル酸、サリチ
ル酸メチル、！−メントール、カン７アー、スリンダッ
ク、トルメチンナトリウム、ナプロキセン、７エンブ７
エンなど、
二）９Ｊ、眠鎮静剤：例えばフェノパルビタール、アモ
パルビタール、シクロパルビタール、トリアプラム、ニ
トラゼパム、ロラゼパム、ハロペリドールなど、
ホ）精神安定剤：例えばフル７エナノン、テオリタノン
、ジアゼパム、フルノアゼパム、フルニトラゼパム、ハ
ロペリドール、クロルプロマジンなど、
へ）抗高血圧剤；例えばクロニジン、塩酸クロニジン、
ピンドロール、プロプラノロール、塩酸プロプラノロー
ル、ブ７ラノール、インデノロール、ニバジピン１、口
７ヱノキシン、ニプラノロール、ブクモロールなど、
ト）降圧利尿剤：例えばハイドロサイアザイド、ペンド
ロンルナサイアザイド、シクロベンチアザイドなど、
チ）抗生物質：例えばペニシリン、テトラサイクリン、
オキシテトラサイクリン、硫酸７ラジオマイシン、エリ
スロマイシン、クロラムフェニコールなど、
す）麻酔剤二例えばりドカイン、塩酸ノブ力イン、ベン
シカイン、アミ７安息香酸エチルなど、ヌ）抗菌性物質
：例えば塩酸ベンザルコニウム、ニトロ７ラゾン、ナイ
スクチン、アセトスルファミン、クロトリマゾールなど
、
ル）抗真菌物質：例えばペンタマイシン、７ムホ？ ’
）シンＢ、ピロールニドリン、クロトリマゾールなど、
ヲ）ビタ・ミン剤：例えばビタミンＡ１エルゴカルシフ
エロール、コレカルシフェロール、オクトチアジン、リ
ボフラビン酪酸エステルなど、ワ）抗てんかん剤：例え
ばニトラゼバム、メプロパメート、クロナゼパムなど、
カ）冠血管拡張剤：例えばニトログリセリン、ニトログ
リコール、イソソルビドジナイトレート、エリスリトー
ルテトラナイトレート、ペンタエリスリトールテトラナ
イトレート、プロパチルナイトレートなど、
ヨ）抗ヒスタミン剤：例えば塩酸ノアエンヒドラミン、
クロルフェニラミン、ノ７ヱニルイミクソールなど、
り）鎮咳剤：例えば臭化水素酸デキストロメトルファン
、硫酸テルプタソン、エフェドリン、塩酸エフェドリン
、硫酸サルブタモール、塩酸イソプロテノール、硫酸イ
ソプロテノールなど、し）性ホルモン：例えばプロプス
テロン、エストラジオールなど、
ン）抗響剤：例えばドキセピンなど
ツ）脳循環改善剤：例えばビデルギン、ニルゴツトアル
カロイド、イアエンプロジルなど、ネ）制吐剤、抗腫瘍
剤：例えばメトクロプラミド、クレボプライド、トンベ
リトン、スフボラミン、臭化水素酸スフボラミン、５−
フルオロウラシル、メルカプトプリンなど、
ナ）生体医薬：例えばポリペプチド１（ＴＲＨ，ＬＨＲ
Ｈの誘導体）、プロスタグランノン類など、う）その他
：例えば７エンタニール、ノボキシン、デスモブレシン
、ジヒドロエルゴタミンメタンスルホン酸、ノヒドロエ
ルゴタミン酒石酸など、が挙げられる。b) Ca” antagonistic FC drugs: 27edipine, nisornovine,
Nohydrobilirine Caz+ antagonists such as nimodipine, nirnovin, nicardipine, inrompin, etc. Flutifsteroids such as hydrocortiscin, prednisolone, beclomethasone propionate, flumethacin, triamci/ron, triamci/ron acetonide, fluocinolone, 7-ruocino Analgesic and anti-inflammatory agents such as ronacetonide, fluocinolone acetonide acetate, clobetasol propionate, etc., such as acetamino-7-ene, mefenamic acid, flufenamic acid, indomethacin, dichlo-7-enac, cyclo-7-enac sodium, alcro-7-enac, oxy 7 Emtazone, 7 Eniluftason, Ibufuro 7 En, Flurbipro 7 En, Salicylic Acid, Methyl Salicylate,! -Menthol, Kan7ar, Sulindac, Tolmetin Sodium, Naproxen, 7emb7
2) 9J, sedatives: e.g. phenoparbital, amoparbital, cycloparbital, triapram, nitrazepam, lorazepam, haloperidol, etc. e) tranquilizers: e.g. flu7enanone, teolitanone, diazepam, flunoazepam, flunitrazepam, haloperidol, chlorpromazine, etc.) antihypertensive agents; for example, clonidine, clonidine hydrochloride,
Pindolol, propranolol, propranolol hydrochloride, b7ranol, indenolol, nivadipine 1, 7enoxine, nipranolol, bucumolol, etc. g) Antihypertensive diuretics: e.g. hydrothiazide, pendron lunathiazide, cyclobenziazide, etc. h) Antibiotics :For example, penicillin, tetracycline,
Oxytetracycline, 7-radiomycin sulfate, erythromycin, chloramphenicol, etc.; 1) Anesthetic agents, such as docaine, nobuirine hydrochloride, benzicaine, ethyl amylbenzoate, etc.; 2) Antibacterial substances, such as benzalkonium hydrochloride. , nitro-7razone, nyscutin, acetosulfamine, clotrimazole, etc.) Antifungal substances: e.g. pentamycin, 7-muho? '
) SynB, pyrrolnidoline, clotrimazole, etc., w) Vitamin A1 drugs: e.g., vitamin A1 ergocalciferol, cholecalciferol, octothiazine, riboflavin butyrate, etc., w) Antiepileptic drugs: e.g., nitrazebam, mepropamate, etc. Clonazepam, etc. f) Coronary vasodilators: e.g. nitroglycerin, nitroglycol, isosorbide dinitrate, erythritol tetranitrate, pentaerythritol tetranitrate, propyl nitrate, etc. e) Antihistamines: e.g. noaenehydramine hydrochloride,
Chlorpheniramine, 7-enyl imixol, etc.; ii) Antitussives: For example, dextromethorphan hydrobromide, terptasone sulfate, ephedrine, ephedrine hydrochloride, salbutamol sulfate, isoprotenol hydrochloride, isoprotenol sulfate, etc.; ii) Sex hormones: For example, propsterone, estradiol, etc. N) Antisounding agents: For example, doxepin. T) Cerebral circulation improving agents: For example, videlgin, nilgot alkaloids, iaenprodil, etc.. tonberitone, sufboramine, sufboramine hydrobromide, 5-
fluorouracil, mercaptopurine, etc. n) Biomedicine: For example, polypeptide 1 (TRH, LHR
(derivatives of H), prostagranones, etc.; c) Others: Examples include 7-entanyl, novoxin, desmobrecin, dihydroergotamine methanesulfonic acid, nohydroergotamine tartrate, and the like.
これらの経皮吸収性を有する薬物のうち、特にジヒドロ
ピリジン系Ｃａ２＋拮抗薬は、後述するカルボキシル基
含有アクリル系粘着剤層との関連において薬理学的に有
効量のＣａ２＋拮抗薬が経皮的に迅速且つ持続的に生体
内に吸収され、その効果が１１者に現れるから最も好ま
しいのである。Among these transdermally absorbable drugs, dihydropyridine-based Ca2+ antagonists in particular can be rapidly transdermally absorbed in pharmacologically effective amounts in conjunction with the carboxyl group-containing acrylic adhesive layer described below. It is most preferable because it is absorbed continuously into the body and its effects appear on 11 people.
即ち、狭心症及び高血圧のような症状に有効な治療効果
をもたらすＣａ２＋拮抗薬はその経皮吸収性が化学的性
質及び物理的性質より相当困難であることより、未だ、
有効な経皮吸収型の製剤は開発されていない。That is, Ca2+ antagonists, which have effective therapeutic effects on symptoms such as angina pectoris and hypertension, are still difficult to absorb through the skin due to their chemical and physical properties.
No effective transdermal formulation has been developed.
本発明の疾患治療用貼付剤は、そのカルボキシル基含有
アクリル系粘着剤層との関連において、特にＣａ”＋拮
抗薬の如き経皮吸収の困難な薬物についても薬理学的有
効量の薬物を迅速に且つ持続的に経皮吸収させうろこと
を実現したものである。The patch for treating diseases of the present invention, in conjunction with its carboxyl group-containing acrylic adhesive layer, can quickly deliver a pharmacologically effective amount of a drug, especially for drugs that are difficult to absorb transdermally, such as Ca''+ antagonists. The scales are able to be absorbed through the skin in a sustained manner.
上記の薬物（Ａ）と高分子物質ＣＢ）との配合割合は当
該（Ａ）が（Ａ ＋ Ｂ ）全体の３〜５０重皿％の範
囲で含有させるのが好ましく、（Ａ）の含有量が、３重
量％未満では薬物の生体内への投与量が少なく治療効果
が乏しい場合があり、一方、５０ｍ１１％を超えると治
療効果に限界が生じると共に不経済であり、いずれも好
ましくないのである。The blending ratio of the drug (A) and the polymer substance CB) is preferably such that (A) is contained in a range of 3 to 50% of the total (A + B), and the content of (A) However, if it is less than 3% by weight, the amount of drug administered into the body may be small and the therapeutic effect may be poor, while if it exceeds 50ml11%, the therapeutic effect will be limited and it will be uneconomical, both of which are undesirable. .
本発明の疾患治療用貼付剤を構成するカルボキシル基含
有アクリル系粘着剤層は上記薬物含有高分子物質層に積
層される層であって、その露出面は適用する皮膚面に貼
付、密着されて、該露出面から薬物を生体内に吸収させ
るものである。The carboxyl group-containing acrylic adhesive layer constituting the patch for disease treatment of the present invention is a layer that is laminated on the drug-containing polymer material layer, and its exposed surface is pasted and brought into close contact with the skin surface to which it is applied. , the drug is absorbed into the body through the exposed surface.
該粘着剤層は（メタ）アクリル酸、マレイン酸、無水マ
レイン酸、イタフン酸、７マール酸などのカルボキシル
基を有する単量体と、粘着性を付与する（メタ）アクリ
ル酸アルキルエステルなどの単量体との共重合体や、上
記カルボキシル基を有する単量体からなる重合体にロジ
ン、石油系樹脂の如き粘着性付与剤、油状物質、多価ア
ルコールの如き可塑剤を添加したり、ポリイソプレン、
ポリイソブチレン、ポリブタノエンの如きゴム成分を適
宜混合しで得ることがで勝る。The adhesive layer contains a monomer having a carboxyl group such as (meth)acrylic acid, maleic acid, maleic anhydride, itafonic acid, and hexamaric acid, and a monomer such as (meth)acrylic acid alkyl ester that imparts adhesiveness. A tackifying agent such as rosin or petroleum resin, an oily substance, or a plasticizer such as polyhydric alcohol may be added to a copolymer with a monomer having a carboxyl group, or a copolymer consisting of a monomer having a carboxyl group. isoprene,
It is advantageous to obtain it by appropriately mixing rubber components such as polyisobutylene and polybutanoene.
これらのうち薬物の安定性や放出性の点から（メタ）ア
クリル酸アルキルエステルと（メタ）アクリル酸との共
重合体が好ましく、該（メタ）アクリル酸アルキルエス
テルのフルキル基の炭素数が４〜１４の範囲の単量体を
使用すると、皮膚面との粘着性、密着性において良好な
結果が得られる。Among these, a copolymer of a (meth)acrylic acid alkyl ester and (meth)acrylic acid is preferred from the viewpoint of drug stability and release properties, and the (meth)acrylic acid alkyl ester has a furkyl group having 4 carbon atoms. When a monomer in the range of 14 to 14 is used, good results can be obtained in terms of adhesion and adhesion to the skin surface.
また、この共重合体の場合、（メタ）アクリル酸アルキ
ルエステル（Ｃ）と（メタ）アクリル酸（Ｄ）との共重
合体の比率は重量比で９９〜７０：１〜３０１特に９９
〜８０：１〜２０の範囲に設定することが好ましい。Further, in the case of this copolymer, the ratio of the copolymer of (meth)acrylic acid alkyl ester (C) and (meth)acrylic acid (D) is 99 to 70:1 to 301 by weight, especially 99
It is preferable to set the ratio in the range of 1 to 20 to 80:1.
上記の（Ｃ）と（Ｄ）の共１合体において、当該（Ｄ）
の比率が、１未満では凝集力不足により皮膚適用時糊残
りなどが起こり好ましくないのであり、一方３０を超え
ると逆に皮膚接着性が劣りそれに伴い経皮からの吸収性
も不足するので好ましくなし１ 。In the combination of (C) and (D) above, the (D)
If the ratio is less than 1, the adhesive will remain when applied to the skin due to insufficient cohesive force, which is undesirable. On the other hand, if it exceeds 30, the skin adhesion will be poor and transdermal absorption will also be insufficient, which is not desirable. 1.
ところで、上記（メタ）アクリル酸アルキルエステルに
おいてそのアルキル基の炭素数が４〜１４の範囲のもの
としては、上述のものが挙げられる。By the way, examples of the above-mentioned (meth)acrylic acid alkyl esters having an alkyl group in the range of 4 to 14 carbon atoms include those mentioned above.
上記カルボキシル基含有アクリル系粘着剤は、薬物の溶
解性の点では決して良好なものではないが、該粘着剤に
薬物を含有させた場合は薬物の放出性が極めて良好であ
り、この粘着剤を本願発明のよ）な貼付剤に利用して皮
膚面側の接着剤層を形成した場合は薬物の皮膚面への放
出、ならびに生体内への薬物の経皮吸収が効果的に行な
われるのである。The above-mentioned carboxyl group-containing acrylic adhesive is by no means good in terms of drug solubility, but when the adhesive contains a drug, the drug release property is extremely good, and this adhesive When used in a patch (like the one of the present invention) to form an adhesive layer on the skin side, the release of the drug to the skin surface and transdermal absorption of the drug into the body are effectively carried out. .
上記カルボキシル基含有アクリル系粘着剤層としては実
質的に経皮吸収性の薬物を含有していないか、もしくは
薬物含有高分子物質層よりも低濃度にて薬物を含有させ
たものが挙げられるのであり、これらのうち薬物を含有
したものが好ましい。The above-mentioned carboxyl group-containing acrylic adhesive layer may contain substantially no transdermally absorbable drug, or may contain a drug at a lower concentration than the drug-containing polymer layer. Of these, those containing drugs are preferred.
この場合、薬物の含有量としては、カルボキシル基含有
アクリル系粘着剤層中に１０重量％以下の範囲で含有さ
せ、これによって、本発明の疾患治療Ｊ１１ｇ材の即効
性を一層実現しうるのである。In this case, the drug content is in the range of 10% by weight or less in the carboxyl group-containing acrylic adhesive layer, thereby further realizing the immediate effect of the disease treatment J11g material of the present invention. .
そして、本発明の疾患治療用貼付剤において、そのカル
ボキシル基含有アクリル系粘着剤層中の薬物濃度は薬物
含有高分子物質層の薬物濃度より低含量として薬物の放
出をコントロールするものである。In the patch for treating diseases of the present invention, the drug concentration in the carboxyl group-containing acrylic adhesive layer is lower than the drug concentration in the drug-containing polymer layer to control drug release.
本発明の疾患治療用貼付剤においてはその皮膚接着層側
のカルボキシル基含有アクリル系粘着剤層のみの通用で
もかなり経皮吸収性は向上するが、一層優れた経皮吸収
性を天現し、充分な薬物の経皮吸収性を確実に達成する
ために、上記粘着剤層中に種々の経皮吸収促進剤を添加
してもよいのである。In the patch for treating diseases of the present invention, the transdermal absorption can be considerably improved even if only the carboxyl group-containing acrylic adhesive layer on the skin adhesive layer side is used. In order to reliably achieve transdermal absorption of the drug, various transdermal absorption enhancers may be added to the adhesive layer.
上記経皮吸収促進剤は、単純には身体面に対する薬物の
放出を促進するものと定義できるが、これには薬物含有
高分子物質層やカルボキシル基含有粘着剤層内において
、薬物の溶解性や拡散性を良好にする機能を有するもの
、また角質の保水性、角質軟化性、角質浸透性（ルーズ
化）、浸透助剤や上孔開孔剤としての機能を有するもの
、皮膚の界面状態を変える機能の如さ経皮吸収性を良く
する機能を有するもの、更に上記の機能を併有し、或い
はこれらの機能に加えて薬物の薬理効果をより高くする
薬効促進の機能をも有しているものなどが包含される。The above-mentioned transdermal absorption enhancer can be simply defined as one that promotes the release of a drug to the body surface. Those that have the function of improving diffusibility, those that have the functions of keratin water retention, keratin softening, keratin permeability (loosening), penetration aids and upper pore opening agents, and those that improve the skin interface condition. Drugs that have the ability to improve transdermal absorption, have the above functions in combination, or have the function of promoting drug efficacy to enhance the pharmacological effects of drugs in addition to these functions. This includes things that exist.
この種の経皮吸収促進助剤としては、例えばメタノール
、エタノール等の低級アルコール、ジエチレングリコー
ル、プロピレンクリコール、ホリエチレングリコール、
ポリプロピレングリコールの如きグリコールｗｉ（主に
薬物溶解性向上）、オリーブ油、スクワレン、う／リン
の如き油曜類（主に薬物拡散性向上）、尿素、７ラント
インの如き尿素溝導体（主に角質層の保水性向上）、ジ
メチルデシルホスホキシド、メチルオクチルスルホキシ
ド、ツメチルスルホキシド、ジメチルホルムアミド、ジ
メチル７セ）７ミド、ツメチルラウリルアミド、ドデシ
ルピロリドン、イソソルビトールのａＩき極性溶剤（主
に角質浸透性向上）、サリチル酸（主に角質軟化性向上
）、アミノ酸（主に角質浸透性向上）、ニコチン酸ベン
ノルエステル（主に上孔開孔剤）、ラウリル硫酸ナトリ
ウム（主に皮膚の界面状態を変化）などが挙げられる。Examples of this type of percutaneous absorption promoting aid include lower alcohols such as methanol and ethanol, diethylene glycol, propylene glycol, polyethylene glycol,
Glycols such as polypropylene glycol (mainly to improve drug solubility), oils such as olive oil, squalene, and phosphorus (mainly to improve drug diffusivity), urea, and urea groove conductors such as 7lantoin (mainly to improve the stratum corneum) dimethyldecyl phosphooxide, methyl octyl sulfoxide, trimethyl sulfoxide, dimethyl formamide, dimethyl 7mide, trimethyl laurylamide, dodecyl pyrrolidone, isosorbitol polar solvents (mainly keratin permeable salicylic acid (mainly improves keratin softening properties), amino acids (mainly improves keratin permeability), nicotinic acid bennorester (mainly pore opening agent), sodium lauryl sulfate (mainly changes skin interface condition) Examples include.
その他ジイソプロピルアノペート、７タル酸エステル、
ノエチルセバケートの如き可塑剤、二）キシ化ステ７リ
ルアルコール、Ｎ−メチルピロリドン、グリセリンエス
テＩし、１−ドデシル−アザシクロへブタン−２−オン
、ミリスチン酸イソプロピル、ラウリル酸エチルなどを
挙げることができる。Others diisopropyl anopate, 7-talic acid ester,
Plasticizers such as noethyl sebacate, di-oxygenated alcohol, N-methylpyrrolidone, glycerinester I, 1-dodecyl-azacyclohebutan-2-one, isopropyl myristate, ethyl laurate, etc. be able to.
これらは必要に応じて二種以上添加することができる。Two or more of these can be added as necessary.
上記経皮吸収促進助剤の添加量は皮膚接着性及び凝集力
とのバランスを考慮して上記薬物、上記粘着剤層及び所
望により加えられた経皮吸収促進助剤の全体重量に対し
て０．１〜３０重１％の範囲とするのが望ましく、添加
量が０．１重量％未満ではその効果が乏しく、又、３０
重１％を超えると皮膚接着性や凝集力が悪化する場合が
あるから好ましくない。The amount of the above-mentioned transdermal absorption-promoting aid is determined to be 0% based on the total weight of the drug, the adhesive layer, and the transdermal absorption-promoting aid added as desired, taking into consideration the balance between skin adhesion and cohesive force. It is desirable that the amount is in the range of 1% to 30% by weight; if the amount added is less than 0.1% by weight, the effect will be poor;
If it exceeds 1% by weight, skin adhesion and cohesive strength may deteriorate, which is not preferable.
（ｅ）作用
本発明の疾患治療用貼付剤において、薬物の経皮吸収が
速やかに行なわれる理由は明確ではないが、皮膚接着面
側のカルボキシル基含有アクリル系粘着剤層中の薬物濃
度を薄くすることにより、当該粘着剤層の皮膚接着性を
良好にすると共にカルボキシル基の作用によって皮膚界
面に変化を与え、これによって、薬物が生体内に持続的
に吸収されるものと解される。(e) Effect: Although it is not clear why the drug is rapidly absorbed through the skin in the patch for treating diseases of the present invention, it is possible to reduce the drug concentration in the carboxyl group-containing acrylic adhesive layer on the skin adhesive side. It is understood that this improves the skin adhesion of the pressure-sensitive adhesive layer and changes the skin interface due to the action of the carboxyl group, thereby allowing the drug to be absorbed into the body in a sustained manner.
又、カルボキシル基含有アクリル系粘着剤層から皮膚面
に薬物が放出、移行することによって当該粘着剤層中の
薬物濃度が低下すると、減少した量の薬物を補うように
濃度差によって薬物含有高分子物質層から薬物が粘着剤
層中へ移行、補給されて薬物濃度を所定の範囲に保持し
、このため薬物を生体内に持続的に経皮吸収させうる作
用を有するのである。In addition, when the drug concentration in the adhesive layer decreases due to release and transfer of the drug from the carboxyl group-containing acrylic adhesive layer to the skin surface, the drug-containing polymer increases due to the concentration difference to compensate for the decreased amount of drug. The drug migrates from the substance layer into the adhesive layer and is replenished to maintain the drug concentration within a predetermined range, thus having the effect of allowing the drug to be continuously absorbed transdermally into the body.
（ｆ）実施例
次に本発明を実施例に基づき詳細に説明するが、本発明
はこれに限定されるものではない。(f) Examples Next, the present invention will be explained in detail based on Examples, but the present invention is not limited thereto.
以下において、部又は％は重量部又は重量％を意味する
。In the following, parts or % mean parts by weight or % by weight.
実施例１
（薬物含有高分子物質層）
窒素〃ス雰囲気下において四つロフラスコ内にアクリル
酸イソノニルエステル６５Ｂ、酢Ｒビニル３５部、酢酸
エチル１００部を仕込み、重合開始剤として７ゾビスイ
ソプチロニトリル（Ａ Ｉ ＢＮ）０．２部を添加し、
浴内温度を６０〜６３℃に維持しなから攪袢と酢酸エチ
ル１３３．３部を徐々に滴下することによって反応ＩＩ
Ｉ ＩＩを行いつつ８時間重合反応を行なった後、更に
内浴温度を７０〜７５℃に昇温しで２時間熟成すること
により共重合体溶液を得た。Example 1 (Drug-containing polymeric material layer) Acrylic acid isononyl ester 65B, 35 parts of vinyl acetate R, and 100 parts of ethyl acetate were placed in a four-bottle flask under a nitrogen atmosphere, and 7zobisisopropylene was added as a polymerization initiator. Add 0.2 parts of tyronitrile (A I BN),
Reaction II was carried out by gradually adding 133.3 parts of ethyl acetate with stirring while maintaining the bath temperature at 60 to 63°C.
After carrying out the polymerization reaction for 8 hours while performing III, the inner bath temperature was further raised to 70 to 75°C and aged for 2 hours to obtain a copolymer solution.
この共重合体の重合率は９２．８％であり、固形分濃度
３０％の共重合体溶液の粘度は温度３０℃で１１０ボイ
ズであった。The polymerization rate of this copolymer was 92.8%, and the viscosity of the copolymer solution with a solid content concentration of 30% was 110 voids at a temperature of 30°C.
得られた共重合体溶液にニアニジピンをその含量が８０
０部ｇ／ａｍ”となるように添加混合し、ポリエチレン
／アルミニウム蒸着フィルム（支持体）のポリエチレン
側に乾燥後の厚みが４０μ−となるように塗布し、温度
１００℃で５分間乾燥しって薬物（ニアニジピン）含有
高分子物質層を積層した。Nianidipine was added to the resulting copolymer solution at a content of 80%.
0 parts g/am", coated on the polyethylene side of a polyethylene/aluminum vapor-deposited film (support) to a dry thickness of 40 μ-, and dried for 5 minutes at a temperature of 100°C. A drug (nianidipine)-containing polymer material layer was then laminated.
（カルボキシル基含有アクリル系粘着剤層）ｎ−ブチル
アクリレ−）９０部及びアクリル酸１０部を用い、上記
と同様に共重合して重合率９９．６％、固形分濃度３０
％の共重合体溶液の粘度が温度３０℃で１６０ボイズの
カルボキシル基含有アクリル系粘着剤溶液を得た。(Carboxyl group-containing acrylic adhesive layer) 90 parts of n-butyl acrylate) and 10 parts of acrylic acid were copolymerized in the same manner as above to achieve a polymerization rate of 99.6% and a solid content concentration of 30.
A carboxyl group-containing acrylic pressure-sensitive adhesive solution with a copolymer solution viscosity of 160 voids at a temperature of 30° C. was obtained.
得られた共重合体溶液にニアニジピンをその含量が５０
μｇ／ｃａｂ”となるように添加混合し、セパレータ上
に乾燥後の厚みが１０μ−となるように塗布し、温度１
００℃で３分間乾燥して薬物（二フェノピン）を含有す
るカルボキシル基含有アクリル系粘着剤層を得た。Nianidipine was added to the resulting copolymer solution at a content of 50%.
μg/cab” and coated on a separator to a dry thickness of 10 μ-.
The mixture was dried at 00° C. for 3 minutes to obtain a carboxyl group-containing acrylic adhesive layer containing a drug (diphenopine).
ここで得られたニアニジピンを含有するカルボキシル基
含有アクリル系粘着剤層を、上記薬物含有高分子物質層
側に転着、積層して本発明の疾患治療用貼付剤を得た。The carboxyl group-containing acrylic adhesive layer containing nianidipine obtained here was transferred and laminated on the drug-containing polymer layer side to obtain a patch for disease treatment of the present invention.
比較例１ａ
上記二７二ノピン含有高分子物質を、上記と同様の支持
体においてそのポリエチレン側に乾燥後の厚みが４０μ
輪となるように塗布、乾燥したものを用いた。Comparative Example 1a The above-mentioned 27-dinopine-containing polymeric material was placed on the polyethylene side of the same support as above with a thickness of 40 μm after drying.
It was applied in a ring and dried.
比較例１ｂ
上記のニアニジピンを含有するカルボキシル基含有アク
リル系粘着剤を用い、上記比較例１ａと同様の方法で得
たものを用いた。その粘着剤層の厚さは４０μ−とした
。Comparative Example 1b The carboxyl group-containing acrylic pressure-sensitive adhesive containing Nianidipine was used, which was obtained in the same manner as in Comparative Example 1a. The thickness of the adhesive layer was 40μ.
実施例２
（薬物含有高分子物質）
実施例１と同様に、２−エチルエキシルアクリレート４
５部、２−エトキシエチルアクリレート３０部及び酢酸
ビニル２５ｇ１Ｓを共１合させて重合率９３％、固形分
濃度３０％の共重合体溶液の粘度が温度３０℃で９５ボ
イズであった。Example 2 (Drug-containing polymeric substance) Similar to Example 1, 2-ethylexyl acrylate 4
5 parts of 2-ethoxyethyl acrylate, 30 parts of vinyl acetate, and 25 g of vinyl acetate were co-merged to obtain a copolymer solution with a polymerization rate of 93% and a solid content concentration of 30%.The viscosity of the copolymer solution was 95 voids at a temperature of 30°C.
得られた共重合体溶液にニアニジピンをその含量が１０
００μｇ／ｃａ＋２となるように添加混合し、ポリエチ
レン／アルミニウム蒸着フィルム（支持体）のアルミニ
ウム側に乾燥後の厚みが４０μ−となるように塗布し、
温度１２０℃で４分間乾燥して薬物にゾルジピン）含有
高分子物質層を得た。Nianidipine was added to the resulting copolymer solution at a content of 10
00μg/ca+2 and coated on the aluminum side of a polyethylene/aluminum vapor-deposited film (support) so that the thickness after drying is 40μ-,
It was dried at a temperature of 120° C. for 4 minutes to obtain a polymer material layer containing zoldipine as a drug.
（カルボキシル基含有アクリル系粘着剤層）上記と同様
にイソオクチルアクリレート９８部及びメタアクリル酸
２部を用い、上記と同様に共重合して重合率９９．２％
、固形分濃度３０％の共重合体溶液の粘度が７０ポイズ
のカルボキシル基含有アクリル系粘着剤を得た。(Carboxyl group-containing acrylic adhesive layer) Using 98 parts of isooctyl acrylate and 2 parts of methacrylic acid in the same manner as above, copolymerization was carried out in the same manner as above to achieve a polymerization rate of 99.2%.
A carboxyl group-containing acrylic pressure-sensitive adhesive having a copolymer solution having a solid content concentration of 30% and a viscosity of 70 poise was obtained.
得られた共重合体溶液に、ニゾルジピン（薬物）とツメ
チルスルホキシドを各々の含量が１００μｇ／ｃｔａ”
、５０μｇ／ａｍ”となるように添加混合し、セパレー
タ上に乾燥後の厚みが２０μ論となるように塗布し、温
度１００℃で５分間乾燥してニゾルジビンを含有するカ
ルボキシル基含有アクリル系粘着剤層を得た。Nizoldipine (drug) and trimethyl sulfoxide were added to the resulting copolymer solution at a content of 100 μg/cta.
, 50 μg/am”, coated on the separator to a dry thickness of 20 μm, and dried at a temperature of 100° C. for 5 minutes to obtain a carboxyl group-containing acrylic adhesive containing nisoldibine. Got layers.
ここで得られたニゾルノピンを含有するカルボキシル基
含有アクリル系粘着剤層を、上記薬物含有高分子物質層
側に転着、積層して本発明の疾患治療用貼付剤を得た。The carboxyl group-containing acrylic adhesive layer containing nisolnopine obtained here was transferred and laminated on the drug-containing polymer layer side to obtain a patch for disease treatment of the present invention.
比較例２ａ
実施例２で得た薬物にゾルノビン）含有高分子物質を、
実施例２と同様の支持体においてそのアルミニウム側に
乾燥後の厚みが４０μ−となるように撒布、乾燥したも
のを用いた。Comparative Example 2a A polymeric substance containing Zornovin was added to the drug obtained in Example 2.
A support similar to that used in Example 2 was sprayed and dried on the aluminum side so that the thickness after drying was 40 μm.
比較例２ｂ
実施例２で得た薬物にゾルノビン）を含有したカルボキ
シル基含有アクリル系粘着剤を用いた以外は比較例２ａ
と同様にして形成したものを用いた。Comparative Example 2b Comparative Example 2a except that a carboxyl group-containing acrylic adhesive containing Zornovin was used as the drug obtained in Example 2.
A material formed in the same manner as above was used.
実施例３
（薬物含有高分子物質層）
２−エステルへキシル７クリレート７５部、１−ビニル
−２−ピロリドン２５部を共重合させて重合率９９．７
％、固形分濃度３０％の共重合体溶液の粘度が温度３０
℃で１２０ボイズの高分子物質溶液を得た。Example 3 (Drug-containing polymer material layer) 75 parts of 2-esterhexyl 7-acrylate and 25 parts of 1-vinyl-2-pyrrolidone were copolymerized to achieve a polymerization rate of 99.7.
%, the viscosity of a copolymer solution with a solid content concentration of 30% is at a temperature of 30%.
A polymer substance solution with 120 voids was obtained at ℃.
得られた高分子物質溶液に薬物（インロンビン）をその
含量が１２００μｇ／Ｃｍ２となるように添加混合し、
ポリエチレンテレフタレート／アルミニウム蒸着フィル
ム（支持体）のアルミニウム側に乾燥後の厚みが５０μ
論となるように塗布し、温度１２０℃で５分間乾燥して
薬物（インロンビン）含有高分子物質層を得た。A drug (inthrombin) was added and mixed to the obtained polymer substance solution so that its content was 1200 μg/Cm2,
The aluminum side of the polyethylene terephthalate/aluminum vapor-deposited film (support) has a thickness of 50 μm after drying.
It was coated in a consistent manner and dried at a temperature of 120° C. for 5 minutes to obtain a drug (inthrombin)-containing polymer material layer.
（カルボキシル基含有アクリル系粘着剤層）イソノニル
アクリレート９５部、アクリル酸５部を共重合させて重
合率９９．６％、固形分濃度３０％の共重合体溶液の粘
度が温度３０℃で１６０ポイズのカルボキシル基含有ア
クリル系粘着剤溶液を得た。(Carboxyl group-containing acrylic adhesive layer) 95 parts of isononyl acrylate and 5 parts of acrylic acid are copolymerized, and the viscosity of the copolymer solution with a polymerization rate of 99.6% and a solid content concentration of 30% is 160 at a temperature of 30°C. A carboxyl group-containing acrylic adhesive solution of Poise was obtained.
得られた共重合体溶液に薬物（イソロンビン）をその含
量が５０μｇ ／ ｃ ｍ ”となるように添加混合し
、セパレータ上に乾燥後の厚みが１０μ曽となるように
塗布し、温度１００℃で３分間乾燥してイソロシピンを
含有するカルボキシル基含有アクリル系粘着剤層を得た
。A drug (isothrombin) was added and mixed to the obtained copolymer solution so that its content was 50 μg/cm, and the mixture was coated on a separator so that the thickness after drying was 10 μm, and the mixture was heated at a temperature of 100°C. After drying for 3 minutes, a carboxyl group-containing acrylic pressure-sensitive adhesive layer containing isolocipine was obtained.
ここで得られたイソロンピンを含有するカルボキシル基
含有アクリル系粘着剤層を、上記薬ｌｌ１（イソロンビ
ン）含有高分子物質層側にＶ、着、積層して本発明の疾
患治療用貼付剤を得た。The carboxyl group-containing acrylic adhesive layer containing isolombine obtained here was V-coated and laminated on the side of the drug ll1 (isothrombin)-containing polymer material layer to obtain a patch for disease treatment of the present invention. .
比較例３ａ
実施例３で得た薬物（イソロンビン）含有高分子物質を
、実施例３と同様の支持体においてそのアルミニウム側
に乾燥後の厚みが５０μｍとなるように塗布、乾燥した
ものを用いた。Comparative Example 3a The drug (isothrombin)-containing polymeric substance obtained in Example 3 was coated on the aluminum side of the same support as in Example 3 so that the thickness after drying was 50 μm, and then dried. .
比較例３ｂ
実施例２で得た薬物にゾルノビン）を含有したカルボキ
シル基含有アクリル系粘着剤を用いた以外は比較例２ａ
と同様にして形成したものを用いた。この場合、粘着剤
層の厚さは４０μ−とした。Comparative Example 3b Comparative Example 2a except that a carboxyl group-containing acrylic adhesive containing Zornovin was used as the drug obtained in Example 2.
A material formed in the same manner as above was used. In this case, the thickness of the adhesive layer was 40 μ-.
上記の各実施例及び各比較例を用い、その各々の皮膚接
着性とウサギに適用した後の血中濃度の経時変化を第１
表に示す。Using each of the above Examples and Comparative Examples, the skin adhesion and blood concentration changes over time after application to rabbits were first evaluated.
Shown in the table.
（以下余白）
第１表
注１）各サンプル（縦５、横５）を上腕部内部に２４時
間貼付し、端末ハプレが無く体毛をほとんど引き抜かに
程度の接着性をＯとし、端末ハ〃しを生じるか、又は体
毛を引き抜く程度の接着性を×とした。(Margin below) Table 1 Note 1) Each sample (5 vertically, 5 horizontally) was pasted on the inside of the upper arm for 24 hours, and the adhesion level was set to O, where there was no terminal bulging and most of the body hair was pulled out. Adhesiveness to the extent that it causes abrasion or pulls out body hair is rated as x.
注２）ウサギ（体重２ ｋｇ）の背部の毛を剃り、１０
０ ｃｍ２の各サンプルを貼り付け、貼り付は後２．４
．８．１２．２４時間後に耳靜脈より血液を採血し、ガ
スクロマトグラフィーによって血中濃度を測定した。Note 2) Shave the back hair of a rabbit (weight 2 kg),
Paste each sample of 0 cm2, paste after 2.4
．． 8.12. After 24 hours, blood was collected from the ear vein and the blood concentration was measured by gas chromatography.
第１表より、各実施例では皮膚面側に接着するカルボキ
シル基含有アクリル系粘着剤層中の薬物の含量が少ない
から皮膚接着性が良好であり、又、薬物の皮膚面への放
出が速やかに行なわれると共に薬物を生体内に持続的に
投与しうろことが認められる。From Table 1, in each example, the content of drug in the carboxyl group-containing acrylic adhesive layer that adheres to the skin side is small, so the skin adhesion is good, and the drug is quickly released to the skin surface. It is recognized that the drug can be administered continuously into the body.
（ｇ）発明の効果
本発明の疾患治療用貼付剤は、上記構成を有し、薬物が
速やかに経皮吸収されて優れた薬理効果を発現するする
のであり、又、カルボキシル基含有アクリル系粘着剤層
から皮膚面に薬物が放出、移行することによって当該粘
着剤層中の薬物濃度が低下すると、減少した量の薬物を
補うように濃度差によって薬物含有高分子物質層から薬
物が粘着剤層中へ移行、補給されて優れた薬理効果を発
揮するのである。(g) Effects of the invention The patch for disease treatment of the present invention has the above-mentioned structure, and the drug is rapidly absorbed transdermally to exhibit excellent pharmacological effects. When the drug concentration in the adhesive layer decreases due to release and migration of the drug from the drug layer to the skin surface, the drug is transferred from the drug-containing polymer material layer to the adhesive layer due to the concentration difference to compensate for the decreased amount of drug. It moves into the body and is replenished, exerting excellent pharmacological effects.
Claims (6)
キシル基含有アクリル系粘着剤層を順次積層してなる貼
付剤であって、上記粘着剤層は実質的に薬物を含有しな
いか、もしくは薬物含有高分子物質層よりも低濃度にて
薬物を含有してなる疾患治療用貼付剤。(1) A patch comprising a drug-containing polymer material layer and a carboxyl group-containing acrylic adhesive layer sequentially laminated on one side of a support, wherein the adhesive layer does not substantially contain a drug or A disease treatment patch containing a drug at a lower concentration than the drug-containing polymer material layer.
タ）アクリル酸アルキルエステルと（メタ）アクリル酸
の共重合体である特許請求の範囲第１項に記載の疾患治
療用貼付剤。(2) The patch for disease treatment according to claim 1, wherein the carboxyl group-containing acrylic adhesive layer is a copolymer of an alkyl (meth)acrylate and (meth)acrylic acid.
〜１４のアルキル基を有するものである特許請求の範囲
１項に記載の疾患治療用貼付剤。(3) (meth)acrylic acid alkyl ester has 4 carbon atoms
The patch for disease treatment according to claim 1, which has 1 to 14 alkyl groups.
ある特許請求の範囲第１項ないし第４項のいずれかに記
載の疾患治療用貼付剤。(4) The patch for disease treatment according to any one of claims 1 to 4, wherein the drug is a dihydropyridine-based Ca^2^+ antagonist.
の範囲で含有されている特許請求の範囲第１項ないし第
４項のいずれかに記載の疾患治療用貼付剤。(5) The drug is 3 to 50% by weight in the drug-containing polymer material layer.
A patch for disease treatment according to any one of claims 1 to 4, which is contained in the following range.
に１０重量％以下含有されている特許請求の範囲第１項
ないし第５項のいずれかに記載の疾患治療用貼付剤。(6) The patch for disease treatment according to any one of claims 1 to 5, wherein the carboxyl group-containing acrylic adhesive layer contains 10% by weight or less of a drug.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP14264087A JPH0818975B2 (en) | 1987-06-08 | 1987-06-08 | Patch for disease treatment |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP14264087A JPH0818975B2 (en) | 1987-06-08 | 1987-06-08 | Patch for disease treatment |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS63307814A true JPS63307814A (en) | 1988-12-15 |
| JPH0818975B2 JPH0818975B2 (en) | 1996-02-28 |
Family
ID=15320053
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP14264087A Expired - Lifetime JPH0818975B2 (en) | 1987-06-08 | 1987-06-08 | Patch for disease treatment |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0818975B2 (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH03120213A (en) * | 1989-10-03 | 1991-05-22 | Nitto Denko Corp | Percutaneous absorption preparation |
| JP2009235065A (en) * | 2008-03-03 | 2009-10-15 | Nipro Patch Co Ltd | Percutaneous absorption promoter, skin treatment agent and percutaneous absorption-type pharmaceutical preparation containing the same |
| JP2011037884A (en) * | 2001-03-16 | 2011-02-24 | Alza Corp | Transdermal patch for administering fentanyl |
| JP2015508813A (en) * | 2012-02-28 | 2015-03-23 | エスケー ケミカルズ カンパニー, リミテッドSk Chemicals Co., Ltd. | Transdermal absorption preparation containing donepezil and method for producing the same |
| US9198877B2 (en) | 2004-03-09 | 2015-12-01 | Mylan Pharmaceuticals, Inc. | Transdermal systems containing multilayer adhesive matrices to modify drug delivery |
| US9492401B2 (en) | 2004-03-09 | 2016-11-15 | Mylan Technologies, Inc. | Transdermal systems containing multilayer adhesive matrices to modify drug delivery |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19940238A1 (en) * | 1999-08-25 | 2001-03-01 | Lohmann Therapie Syst Lts | Therapeutic system containing active ingredients for application to the skin with at least two polymer-containing layers |
-
1987
- 1987-06-08 JP JP14264087A patent/JPH0818975B2/en not_active Expired - Lifetime
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH03120213A (en) * | 1989-10-03 | 1991-05-22 | Nitto Denko Corp | Percutaneous absorption preparation |
| JP2697191B2 (en) * | 1989-10-03 | 1998-01-14 | 日東電工株式会社 | Transdermal formulation |
| JP2011037884A (en) * | 2001-03-16 | 2011-02-24 | Alza Corp | Transdermal patch for administering fentanyl |
| JP2012197302A (en) * | 2001-03-16 | 2012-10-18 | Alza Corp | Transdermal patch for administering fentanyl |
| US9198877B2 (en) | 2004-03-09 | 2015-12-01 | Mylan Pharmaceuticals, Inc. | Transdermal systems containing multilayer adhesive matrices to modify drug delivery |
| US9205062B2 (en) | 2004-03-09 | 2015-12-08 | Mylan Pharmaceuticals, Inc. | Transdermal systems containing multilayer adhesive matrices to modify drug delivery |
| US9492401B2 (en) | 2004-03-09 | 2016-11-15 | Mylan Technologies, Inc. | Transdermal systems containing multilayer adhesive matrices to modify drug delivery |
| JP2009235065A (en) * | 2008-03-03 | 2009-10-15 | Nipro Patch Co Ltd | Percutaneous absorption promoter, skin treatment agent and percutaneous absorption-type pharmaceutical preparation containing the same |
| JP2015508813A (en) * | 2012-02-28 | 2015-03-23 | エスケー ケミカルズ カンパニー, リミテッドSk Chemicals Co., Ltd. | Transdermal absorption preparation containing donepezil and method for producing the same |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0818975B2 (en) | 1996-02-28 |
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