JPH0530465B2 - - Google Patents
Info
- Publication number
- JPH0530465B2 JPH0530465B2 JP58039516A JP3951683A JPH0530465B2 JP H0530465 B2 JPH0530465 B2 JP H0530465B2 JP 58039516 A JP58039516 A JP 58039516A JP 3951683 A JP3951683 A JP 3951683A JP H0530465 B2 JPH0530465 B2 JP H0530465B2
- Authority
- JP
- Japan
- Prior art keywords
- water
- drug
- acrylic acid
- solution
- weight
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 229940079593 drug Drugs 0.000 claims description 42
- 239000003814 drug Substances 0.000 claims description 42
- 239000000126 substance Substances 0.000 claims description 34
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 17
- 239000000203 mixture Substances 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 238000010521 absorption reaction Methods 0.000 claims description 8
- 239000000463 material Substances 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 3
- 239000002998 adhesive polymer Substances 0.000 claims 2
- 239000000243 solution Substances 0.000 description 23
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- ZNIFSRGNXRYGHF-UHFFFAOYSA-N Clonidine hydrochloride Chemical compound Cl.ClC1=CC=CC(Cl)=C1NC1=NCCN1 ZNIFSRGNXRYGHF-UHFFFAOYSA-N 0.000 description 10
- 229960002925 clonidine hydrochloride Drugs 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000000178 monomer Substances 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- HOBWAPHTEJGALG-JKCMADFCSA-N [(1r,5s)-8-methyl-8-azoniabicyclo[3.2.1]octan-3-yl] 3-hydroxy-2-phenylpropanoate;sulfate Chemical compound [O-]S([O-])(=O)=O.C([C@H]1CC[C@@H](C2)[NH+]1C)C2OC(=O)C(CO)C1=CC=CC=C1.C([C@H]1CC[C@@H](C2)[NH+]1C)C2OC(=O)C(CO)C1=CC=CC=C1 HOBWAPHTEJGALG-JKCMADFCSA-N 0.000 description 8
- -1 atropine sulfate Chemical compound 0.000 description 8
- 229960002028 atropine sulfate Drugs 0.000 description 8
- 229960001193 diclofenac sodium Drugs 0.000 description 8
- 229920000642 polymer Polymers 0.000 description 8
- JGMJQSFLQWGYMQ-UHFFFAOYSA-M sodium;2,6-dichloro-n-phenylaniline;acetate Chemical compound [Na+].CC([O-])=O.ClC1=CC=CC(Cl)=C1NC1=CC=CC=C1 JGMJQSFLQWGYMQ-UHFFFAOYSA-M 0.000 description 8
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 7
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 6
- 239000000853 adhesive Substances 0.000 description 5
- 230000001070 adhesive effect Effects 0.000 description 5
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 230000036470 plasma concentration Effects 0.000 description 4
- 239000002861 polymer material Substances 0.000 description 4
- 238000001556 precipitation Methods 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 208000010201 Exanthema Diseases 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-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
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- 201000005884 exanthem Diseases 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000003505 polymerization initiator Substances 0.000 description 3
- 206010037844 rash Diseases 0.000 description 3
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 2
- OMIGHNLMNHATMP-UHFFFAOYSA-N 2-hydroxyethyl prop-2-enoate Chemical compound OCCOC(=O)C=C OMIGHNLMNHATMP-UHFFFAOYSA-N 0.000 description 2
- HFCUBKYHMMPGBY-UHFFFAOYSA-N 2-methoxyethyl prop-2-enoate Chemical compound COCCOC(=O)C=C HFCUBKYHMMPGBY-UHFFFAOYSA-N 0.000 description 2
- 239000004342 Benzoyl peroxide Substances 0.000 description 2
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 235000019400 benzoyl peroxide Nutrition 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 150000003840 hydrochlorides Chemical class 0.000 description 2
- 239000004745 nonwoven fabric Substances 0.000 description 2
- 239000002985 plastic film Substances 0.000 description 2
- 229920006255 plastic film Polymers 0.000 description 2
- 230000000379 polymerizing effect Effects 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 2
- ZGSZBVAEVPSPFM-FFHNEAJVSA-N (4r,4ar,7s,7ar,12bs)-9-methoxy-3-methyl-2,4,4a,5,6,7,7a,13-octahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-7-ol;2,3-dihydroxybutanedioic acid Chemical compound OC(=O)C(O)C(O)C(O)=O.C([C@H]1[C@H](N(CC[C@@]112)C)C3)C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC ZGSZBVAEVPSPFM-FFHNEAJVSA-N 0.000 description 1
- DKSZLDSPXIWGFO-BLOJGBSASA-N (4r,4ar,7s,7ar,12bs)-9-methoxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-7-ol;phosphoric acid;hydrate Chemical compound O.OP(O)(O)=O.OP(O)(O)=O.C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC.C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC DKSZLDSPXIWGFO-BLOJGBSASA-N 0.000 description 1
- FFTQFHULPHYOIS-UHFFFAOYSA-N (8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 3-acetyloxy-2-phenylpropanoate Chemical compound CN1C(C2)CCC1CC2OC(=O)C(COC(C)=O)C1=CC=CC=C1 FFTQFHULPHYOIS-UHFFFAOYSA-N 0.000 description 1
- GJHKWLSRHNWTAN-UHFFFAOYSA-N 1-ethoxy-4-(4-pentylcyclohexyl)benzene Chemical compound C1CC(CCCCC)CCC1C1=CC=C(OCC)C=C1 GJHKWLSRHNWTAN-UHFFFAOYSA-N 0.000 description 1
- CIVCELMLGDGMKZ-UHFFFAOYSA-N 2,4-dichloro-6-methylpyridine-3-carboxylic acid Chemical compound CC1=CC(Cl)=C(C(O)=O)C(Cl)=N1 CIVCELMLGDGMKZ-UHFFFAOYSA-N 0.000 description 1
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-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
- GOXQRTZXKQZDDN-UHFFFAOYSA-N 2-Ethylhexyl acrylate Chemical compound CCCCC(CC)COC(=O)C=C GOXQRTZXKQZDDN-UHFFFAOYSA-N 0.000 description 1
- PTJDGKYFJYEAOK-UHFFFAOYSA-N 2-butoxyethyl prop-2-enoate Chemical compound CCCCOCCOC(=O)C=C PTJDGKYFJYEAOK-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
- AKUVRZKNLXYTJX-UHFFFAOYSA-N 3-benzylazetidine Chemical compound C=1C=CC=CC=1CC1CNC1 AKUVRZKNLXYTJX-UHFFFAOYSA-N 0.000 description 1
- WHNPOQXWAMXPTA-UHFFFAOYSA-N 3-methylbut-2-enamide Chemical compound CC(C)=CC(N)=O WHNPOQXWAMXPTA-UHFFFAOYSA-N 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 1
- DBAKFASWICGISY-BTJKTKAUSA-N Chlorpheniramine maleate Chemical compound OC(=O)\C=C/C(O)=O.C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 DBAKFASWICGISY-BTJKTKAUSA-N 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- DHUZAAUGHUHIDS-ONEGZZNKSA-N Isomyristicin Chemical compound COC1=CC(\C=C\C)=CC2=C1OCO2 DHUZAAUGHUHIDS-ONEGZZNKSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 description 1
- FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 description 1
- PYGXUPRQBBNETH-UHFFFAOYSA-N acetic acid;2-hydroxypropyl prop-2-enoate Chemical compound CC(O)=O.CC(O)COC(=O)C=C PYGXUPRQBBNETH-UHFFFAOYSA-N 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 150000001649 bromium compounds Chemical class 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
- HOZOZZFCZRXYEK-GSWUYBTGSA-M butylscopolamine bromide Chemical compound [Br-].C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3[N+]([C@H](C2)[C@@H]2[C@H]3O2)(C)CCCC)=CC=CC=C1 HOZOZZFCZRXYEK-GSWUYBTGSA-M 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 229940046978 chlorpheniramine maleate Drugs 0.000 description 1
- 229960001657 chlorpromazine hydrochloride Drugs 0.000 description 1
- IVHBBMHQKZBJEU-UHFFFAOYSA-N cinchocaine hydrochloride Chemical compound [Cl-].C1=CC=CC2=NC(OCCCC)=CC(C(=O)NCC[NH+](CC)CC)=C21 IVHBBMHQKZBJEU-UHFFFAOYSA-N 0.000 description 1
- 229960004415 codeine phosphate Drugs 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000007334 copolymerization reaction Methods 0.000 description 1
- 150000004292 cyclic ethers Chemical class 0.000 description 1
- 229940045574 dibucaine hydrochloride Drugs 0.000 description 1
- 229960000920 dihydrocodeine Drugs 0.000 description 1
- 229960000525 diphenhydramine hydrochloride Drugs 0.000 description 1
- 229960001446 distigmine Drugs 0.000 description 1
- GJHSNEVFXQVOHR-UHFFFAOYSA-L distigmine bromide Chemical compound [Br-].[Br-].C=1C=C[N+](C)=CC=1OC(=O)N(C)CCCCCCN(C)C(=O)OC1=CC=C[N+](C)=C1 GJHSNEVFXQVOHR-UHFFFAOYSA-L 0.000 description 1
- GMSCBRSQMRDRCD-UHFFFAOYSA-N dodecyl 2-methylprop-2-enoate Chemical compound CCCCCCCCCCCCOC(=O)C(C)=C GMSCBRSQMRDRCD-UHFFFAOYSA-N 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- UIWXSTHGICQLQT-UHFFFAOYSA-N ethenyl propanoate Chemical compound CCC(=O)OC=C UIWXSTHGICQLQT-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000003311 flocculating effect Effects 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- LNMQRPPRQDGUDR-UHFFFAOYSA-N hexyl prop-2-enoate Chemical compound CCCCCCOC(=O)C=C LNMQRPPRQDGUDR-UHFFFAOYSA-N 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- LVHBHZANLOWSRM-UHFFFAOYSA-N methylenebutanedioic acid Natural products OC(=O)CC(=C)C(O)=O LVHBHZANLOWSRM-UHFFFAOYSA-N 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- OIXVKQDWLFHVGR-WQDIDPJDSA-N neomycin B sulfate Chemical compound OS(O)(=O)=O.N[C@@H]1[C@@H](O)[C@H](O)[C@H](CN)O[C@@H]1O[C@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](N)C[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CN)O2)N)O[C@@H]1CO OIXVKQDWLFHVGR-WQDIDPJDSA-N 0.000 description 1
- MDYPDLBFDATSCF-UHFFFAOYSA-N nonyl prop-2-enoate Chemical compound CCCCCCCCCOC(=O)C=C MDYPDLBFDATSCF-UHFFFAOYSA-N 0.000 description 1
- KSCKTBJJRVPGKM-UHFFFAOYSA-N octan-1-olate;titanium(4+) Chemical compound [Ti+4].CCCCCCCC[O-].CCCCCCCC[O-].CCCCCCCC[O-].CCCCCCCC[O-] KSCKTBJJRVPGKM-UHFFFAOYSA-N 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
- 239000000123 paper Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960002511 phenobarbital sodium Drugs 0.000 description 1
- WRLGYAWRGXKSKG-UHFFFAOYSA-M phenobarbital sodium Chemical compound [Na+].C=1C=CC=CC=1C1(CC)C(=O)NC([O-])=NC1=O WRLGYAWRGXKSKG-UHFFFAOYSA-M 0.000 description 1
- 229920006267 polyester film Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 229960005439 propantheline bromide Drugs 0.000 description 1
- 229960004482 quinidine sulfate Drugs 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229950009846 scopolamine butylbromide Drugs 0.000 description 1
- 229960004499 scopolamine hydrobromide Drugs 0.000 description 1
- WTGQALLALWYDJH-MOUKNHLCSA-N scopolamine hydrobromide (anhydrous) Chemical compound Br.C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 WTGQALLALWYDJH-MOUKNHLCSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 229960001196 thiotepa Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 229920001567 vinyl ester resin Polymers 0.000 description 1
- 239000002759 woven fabric Substances 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Materials For Medical Uses (AREA)
Description
【発明の詳細な説明】 本発明は外用部材の製法に関するものである。[Detailed description of the invention] TECHNICAL FIELD The present invention relates to a method for manufacturing a member for external use.
従来このタイプの医療用外用部材としては、直
接高分子物質層中に薬物を添加するか、あらかじ
め形成させた高分子物質層表面に適当な溶媒に溶
解した薬物溶液を塗布する方法などで製造されて
いる。 Conventionally, this type of external medical component has been manufactured by adding a drug directly into a polymer material layer, or by applying a drug solution dissolved in an appropriate solvent onto the surface of a pre-formed polymer material layer. ing.
しかして直接薬物を高分子物質中に添加して医
療用外用部材を製造する場合、水溶性薬物は高分
子物質層中で大半が未溶解状態で存在するため
に、含量の均一性や放出性に欠けるものである。
また適当な溶媒に薬物を溶解させて高分子物質表
面に塗布する方法を採用する場合、溶媒が高分子
物質に対して適度の親和性（相溶性）を有してい
ることが薬物を高分子物質層表面上に析出させな
いために必要であるが、親油性の高分子物質表面
に水溶性薬物溶液を塗布すると吸着せずに表面に
析出する欠点を有する。 However, when manufacturing external medical parts by adding drugs directly into polymeric substances, water-soluble drugs exist mostly in an undissolved state in the polymeric substance layer, so the content is not uniform and the release rate is not uniform. This is something that is lacking.
In addition, when adopting a method of dissolving a drug in an appropriate solvent and applying it to the surface of a polymeric material, it is important that the solvent has an appropriate affinity (compatibility) for the polymeric material. Although it is necessary to prevent the drug from being deposited on the surface of the substance layer, it has the disadvantage that when a water-soluble drug solution is applied to the surface of a lipophilic polymeric substance, it will not be adsorbed and will be deposited on the surface.
本発明者らはかかる観点より鋭意研究を重ねた
結果、塩酸クロニジンなどの塩酸塩や、硫酸アト
ロピンなどの硫酸塩、その他の水溶性薬物を水に
対して飽和溶解度以下に溶解させたのち、常温で
粘着性を有する高分子物質の有機溶剤溶液中に添
加混合して均一に溶解させたのち担体体上に該高
分子物質層を形成させることにより、含量の不均
一性が解消され、又外用部材中での水溶性薬物の
析出がなく、放出性に優れた外用部材が得られる
ことを見い出した。 As a result of intensive research from this viewpoint, the present inventors have found that after dissolving hydrochloride salts such as clonidine hydrochloride, sulfates such as atropine sulfate, and other water-soluble drugs to below the saturation solubility in water, By adding and mixing a sticky polymeric substance into an organic solvent solution and uniformly dissolving it, and then forming a layer of the polymeric substance on a carrier, non-uniformity in content can be eliminated, and it can also be used for external use. It has been found that a member for external use with excellent release properties can be obtained without precipitation of water-soluble drugs in the member.
即ち本発明は、（メタ）アクリル酸アルキルエ
ステルを主成分とし、吸水率が25℃で10w／ｗ
％／24h以下である粘着性高分子物質溶液に水溶
性薬物の水及び／又はアルコール溶液を溶解して
なる混合物を担持体面に塗設してなる外用部材の
製法を提供するものである。 That is, the present invention contains (meth)acrylic acid alkyl ester as the main component, and has a water absorption rate of 10 w/w at 25°C.
%/24h or less, and a mixture prepared by dissolving a water and/or alcohol solution of a water-soluble drug in a solution of a sticky polymeric substance and applying the mixture to the surface of a carrier.
本発明の製法によれば、粘着性高分子物質層中
に水溶性薬物が均一に存在する外用部材が簡単な
工程で得られ、しかも均一な放出性を有する外用
部材が得られるものである。 According to the manufacturing method of the present invention, an external member in which a water-soluble drug is uniformly present in the adhesive polymeric substance layer can be obtained through a simple process, and an external member with uniform release properties can be obtained.
本発明に用いられる担持体としては、各種プラ
スチツクフイルムや、不織布、織布、紙、金属箔
又はこれとプラスチツクフイルムとの積層フイル
ムなどが使用される。 As the carrier used in the present invention, various types of plastic films, nonwoven fabrics, woven fabrics, paper, metal foils, or laminated films of these and plastic films are used.
本発明で用いられる粘着性高分子物質として
は、（メタ）アクリル酸アルキルエステルを主成
分とした重合物であり、更に詳しくは（メタ）ア
クリル酸エチルエステル、（メタ）アクリル酸ブ
チルエステル、（メタ）アクリル酸プロピルエス
テル、（メタ）アクリル酸ペンチルエステル、（メ
タ）アクリル酸ヘキシルエステル、（メタ）アク
リル酸オクチルエステル、（メタ）アクリル酸２
−エチルヘキシルエステル、（メタ）アクリル酸
ノニルエステル、（メタ）アクリル酸デシルエス
テル、（メタ）アクリル酸ドデシルエステル、（メ
タ）アクリル酸ステマリルエステルなどの（メ
タ）アクリル酸アルキルエステル単量体を１種又
は２種以上の組み合わせて重合してなるものであ
る。 The adhesive polymeric substance used in the present invention is a polymer mainly composed of alkyl (meth)acrylate, and more specifically, ethyl (meth)acrylate, butyl (meth)acrylate, ( meth)acrylic acid propyl ester, (meth)acrylic acid pentyl ester, (meth)acrylic acid hexyl ester, (meth)acrylic acid octyl ester, (meth)acrylic acid 2
- (meth)acrylic acid alkyl ester monomers such as ethylhexyl ester, (meth)acrylic acid nonyl ester, (meth)acrylic acid decyl ester, (meth)acrylic acid dodecyl ester, (meth)acrylic acid stemaryl ester, etc. It is formed by polymerizing a species or a combination of two or more species.
また前記高分子物質に凝集性をより付加させる
ために、（メタ）アクリル酸、イタコン酸、マレ
イン酸、無水マレイン酸、アクリル酸ヒドロキシ
エチルエステル、アクリル酸ヒドロキシプロピル
エステル、（メタ）アクリルアミド、ジメチルア
クリルアミドの如き官能性単量体や、アクリロニ
トリル、酢酸ビニル、プロピオン酸ビニルの如き
ビニルエステル系単量体などを前記（メタ）アク
リル酸アルキルエステル単量体に共重合すること
ができる。 In addition, in order to add more flocculating properties to the polymeric substance, (meth)acrylic acid, itaconic acid, maleic acid, maleic anhydride, acrylic acid hydroxyethyl ester, acrylic acid hydroxypropyl ester, (meth)acrylamide, dimethylacrylamide Functional monomers such as, vinyl ester monomers such as acrylonitrile, vinyl acetate, and vinyl propionate can be copolymerized with the alkyl (meth)acrylate monomer.
また薬物の溶解性向上を目的として、アクリル
酸メトキシエチルエステル、アクリル酸エトキシ
エチルエステル、アクリル酸ブトキシエチルエス
テルなどの親水性アクリル酸アルコキシアルキル
エステル単量体を共重合成分として使用すること
も可能である。 In addition, for the purpose of improving drug solubility, hydrophilic acrylic acid alkoxyalkyl ester monomers such as acrylic acid methoxyethyl ester, acrylic acid ethoxyethyl ester, acrylic acid butoxyethyl ester, etc. can be used as a copolymerization component. be.
上記単量体を単独重合又は共重合した常温で粘
着性を有する高分子物質、又は２種以上の重合物
を混合した常温で粘着性を付与させた高分子物質
としては、皮膚接着性、凝集性などのバランスを
保つうえで25℃での吸水率が10w／ｗ％／24h以
下のものを選択するのが望ましいものである。こ
こでいう吸水率とは、25℃の水温にて５cm×５cm
の大きさに裁断した高分子物質試験片を水中に浸
漬し、24時間後の重量増加分と浸漬前の重量との
比で定義される。 Polymer substances that are homopolymerized or copolymerized with the above monomers and have tackiness at room temperature, or mixtures of two or more polymers that have tackiness at room temperature include skin adhesion, aggregation, etc. In order to maintain a balance in properties, it is desirable to select a material with a water absorption rate of 10w/w%/24h or less at 25°C. The water absorption rate here refers to 5cm x 5cm at a water temperature of 25℃.
It is defined as the ratio of the weight increase after 24 hours to the weight before immersion by immersing a polymeric substance test piece cut into a size of 2 in water.
本発明に用いられる薬物は水溶性薬物であり、
水及び又はアルコール類を溶媒とした溶液の形で
上記高分子物質溶液中に添加混合される。ここで
いう水溶性薬物の「水溶性」とは、日本薬局方の
通則にて溶解性を示す用語として定義されている
「極めて溶けやすい」、「溶けやすい」、「やや溶け
やすい」性質を有することであり、具体的には粉
末化した薬物を水中に入れ、20±５℃で５分間毎
に強く30秒間振り混ぜた時、30分以内に１ｇ又は
１mlの薬物が30ml末満の水に溶解することをい
う。 The drug used in the present invention is a water-soluble drug,
It is added and mixed into the above polymer substance solution in the form of a solution using water and/or alcohol as a solvent. The "water-soluble" of water-soluble drugs here refers to the properties of "extremely soluble,""easilysoluble," and "slightly soluble," which are defined as terms indicating solubility in the general rules of the Japanese Pharmacopoeia. Specifically, when a powdered drug is placed in water and shaken vigorously for 30 seconds every 5 minutes at 20±5°C, 1 g or 1 ml of the drug will be added to 30 ml of water within 30 minutes. It means to dissolve.
具体的な水溶性薬物としては、塩酸エフエドリ
ン、塩酸クロルプロマジン、塩酸クロニジン、塩
酸ジフエンヒドラミン、塩酸ジブカイン、塩酸ブ
レオマイシンなどの塩酸塩や、硫酸アトロピン、
硫酸キニジン、硫酸フラジオマイシンなどの硫酸
塩、臭化水素酸スコポラミン、臭化ブチルスコポ
ラミン、臭化ジスチグミン、臭化プロパンテリ
ン、などの臭化物、フエノバルビタール−ナトリ
ウム、ジクロフエナツク−ナトリウムなどのアル
カリ金属塩、その他マレイン酸クロルフエニラミ
ン、リン酸コデイン、リン酸ジヒドロコデイン、
チオテパなどが挙げられ、特に塩酸クロニジンを
用いた場合良好な結果が得られる。 Specific water-soluble drugs include hydrochlorides such as efuedrine hydrochloride, chlorpromazine hydrochloride, clonidine hydrochloride, diphenhydramine hydrochloride, dibucaine hydrochloride, and bleomycin hydrochloride, atropine sulfate,
Sulfates such as quinidine sulfate and fradiomycin sulfate; bromides such as scopolamine hydrobromide, butyl scopolamine bromide, distigmine bromide, and propantheline bromide; alkali metal salts such as phenobarbital sodium and diclofenac sodium; Others chlorpheniramine maleate, codeine phosphate, dihydrocodeine phosphate,
Examples include thiotepa, and particularly good results are obtained when clonidine hydrochloride is used.
本発明の製法で得られる外用部材は、常温で粘
着性を有する高分子物質の有機溶剤溶液に固形分
で0.5〜20重量％の水溶性薬物溶液を添加混合し、
担持体上に形成させるものであり、詳しくは前記
水溶性薬物を溶媒に飽和溶解度以下に溶解させた
のち、常温で粘着性を有する高分子物質溶液中に
添加混合して均一に溶解させたのち担持体上に形
成させたものである。 The external member obtained by the production method of the present invention is obtained by adding and mixing a water-soluble drug solution with a solid content of 0.5 to 20% by weight to an organic solvent solution of a polymeric substance that is sticky at room temperature.
It is formed on a carrier. Specifically, the water-soluble drug is dissolved in a solvent below its saturation solubility, and then added and mixed into a solution of a polymeric substance that is sticky at room temperature to uniformly dissolve it. It is formed on a carrier.
水溶性薬物の溶媒は水及び／又はアルコール類
が望ましく、混液の場合は高分子物質との相溶性
の点よりアルコール類が多いほど水溶性薬物の溶
解性が良好であり、薬物含有高分子物質層中の薬
物の含量を高めることができる。 The solvent for water-soluble drugs is preferably water and/or alcohol, and in the case of a mixed solution, the more alcohol there is, the better the solubility of the water-soluble drug is, in terms of compatibility with the polymeric substance. The content of drug in the layer can be increased.
高分子物質溶液の溶媒は高分子物質を調製（重
合）する溶媒や、水溶性薬物溶液との混合時の相
溶性の点から他の溶媒に置換、又は他の溶媒を添
加しても良いが、望ましくは酢酸エチル、トルエ
ン、アセトン、アルコール類、鎖状エーテル類、
環状エーテル類の群から１種又は２種以上が組み
合わせて使用される。 The solvent for the polymeric substance solution may be replaced with or added to the solvent for preparing (polymerizing) the polymeric substance or from the viewpoint of compatibility when mixed with the water-soluble drug solution. , preferably ethyl acetate, toluene, acetone, alcohols, chain ethers,
One type or a combination of two or more types from the group of cyclic ethers are used.
本発明の製法によれば上記のように調整された
薬物含有高分子物質層は、薬物を良溶媒にて溶液
状態にして高分子物質溶液中に配合して製造する
ため、薬物は高分子物質への溶解度以上の状態、
即ち過飽和状態で含有させることができ、高濃度
の薬物を含有する医療用の外用部材が得られるも
のである。 According to the manufacturing method of the present invention, the drug-containing polymeric material layer prepared as described above is manufactured by making the drug into a solution state in a good solvent and blending it into the polymeric material solution. state of solubility or higher in
In other words, it is possible to contain the drug in a supersaturated state, resulting in a medical external member containing a high concentration of the drug.
従つて、薬物量に起因して疾患治療に必要な血
中濃度にあげることができないという不都合を解
消でき、疾患治療に充分な血中濃度を提供するこ
とが出来る。 Therefore, it is possible to eliminate the inconvenience of not being able to raise the blood concentration necessary for disease treatment due to the drug amount, and it is possible to provide a blood concentration sufficient for disease treatment.
高分子物質層中での薬物は保溶媒状態で均一に
溶解されているので未溶解、結晶化が防止され、
含量の均一性並びに薬物の放出性の良好な医療用
の外用部材が得られる。 The drug in the polymer material layer is uniformly dissolved in a solvent-retaining state, preventing it from undissolving and crystallizing.
A medical external member with good uniformity of content and good drug release properties can be obtained.
本発明の製法により得られる外用部材から薬物
をより多く放出させるために、プロピレングリコ
ール、ジエチレングリコール、エタノールの如き
アルコール類、サリチル酸、尿素、ジメチルスル
ホキシド、ジメチルアセトアミド、ジメチルホル
ムアミド、ジエチルセバケート、界面活性剤の如
き助剤を１種以上添加することが出来るが、皮膚
接着性、凝集性などを考慮すると、これらの添加
量は高分子物質に対して0.5〜20重量％の範囲で
添加するのが望ましい。 In order to release more drugs from the external use member obtained by the manufacturing method of the present invention, alcohols such as propylene glycol, diethylene glycol, and ethanol, salicylic acid, urea, dimethyl sulfoxide, dimethylacetamide, dimethylformamide, diethyl sebacate, and surfactants are used. It is possible to add one or more types of auxiliary agents such as, but considering skin adhesion, cohesiveness, etc., it is desirable to add these in an amount in the range of 0.5 to 20% by weight based on the polymer material. .
本発明の製法にて得られた外用部材は適用皮膚
面に貼付した後、含有する水溶性薬物が有効に放
出され、充分な薬理効果を発揮し、しかも薬物の
安定性、溶解性が良好なものである。更に適用皮
膚面より外用部材を除去する際、高分子物質が適
用皮膚面に残存することがなく、しかも皮膚接着
性などの特性が良好なものである。 After being applied to the applied skin surface, the externally used member obtained by the manufacturing method of the present invention effectively releases the water-soluble drug contained therein, exhibits sufficient pharmacological effects, and has good drug stability and solubility. It is something. Further, when the external member is removed from the skin surface to which it is applied, the polymeric substance does not remain on the skin surface to which it is applied, and furthermore, it has good properties such as skin adhesion.
以下に本発明を実施例によりさらに詳しく説明
するが、本発明はこれらの実施例に限定されるも
のではなく、本発明の技術的思想を逸脱しない範
囲で種々の応用が可能である。 EXAMPLES The present invention will be explained in more detail below with reference to Examples, but the present invention is not limited to these Examples, and various applications are possible without departing from the technical idea of the present invention.
実施例 １
アクリル酸２−エチルヘキシルエステル90重量
部、アクリル酸10重量部よりなる単量体混合物に
対し、重合開始剤としてAIBN（アゾビスイソブ
チロニトリル）を0.2重量部用い、酢酸エチル中
にて60℃に昇温して重合させ、８時間反応後さら
に75〜80℃に昇温し、２時間熟成して常温で粘着
性を有する高分子物質の酢酸エチル溶液を得た。Example 1 A monomer mixture consisting of 90 parts by weight of acrylic acid 2-ethylhexyl ester and 10 parts by weight of acrylic acid was dissolved in ethyl acetate using 0.2 parts by weight of AIBN (azobisisobutyronitrile) as a polymerization initiator. After reaction for 8 hours, the temperature was further raised to 75-80°C and aged for 2 hours to obtain an ethyl acetate solution of a polymeric substance that was sticky at room temperature.
吸水率は1.4w／ｗ％／24hであつた。 The water absorption rate was 1.4w/w%/24h.
次にこのようにして得られた高分子物質溶液
（該物質に対する塩酸クロニジンの飽和溶解量は
約２重量％である）に飽和溶解度以下に調製され
た塩酸クロニジン水溶液を添加混合し、ポリエス
テルフイルムの表面に乾燥後の厚みが40μｍとな
るように塗布、乾燥させ、水溶性薬物含有の外用
部材を得た。本実施例で使用した塩酸クロニジン
の添加量は120μｇ／cm2（塩酸クロニジン含有量
約３重量％）となるように設定した。 Next, an aqueous solution of clonidine hydrochloride prepared to have a saturation solubility or less is added to the polymer substance solution obtained in this way (the saturated dissolution amount of clonidine hydrochloride in the substance is about 2% by weight), and the mixture is mixed to form a polyester film. It was coated on the surface to a dry thickness of 40 μm and dried to obtain a water-soluble drug-containing member for external use. The amount of clonidine hydrochloride used in this example was set to 120 μg/cm 2 (clonidine hydrochloride content: approximately 3% by weight).
得られた外用部材中で塩酸クロニジンの溶解性
は良好であり、未溶解物や結晶の析出は観察され
ず、経日変化における塩酸クロニジンの安定性は
極めて良好であつた。更に貼着適用した場合の塩
酸クロニジンの放出性も良好で治療に充分な有効
血漿中濃度が得られた。また剥離除去した後の糊
残り現象や適用皮膚面のカブレなどはなかつた。 The solubility of clonidine hydrochloride in the obtained external use member was good, no undissolved substances or precipitation of crystals were observed, and the stability of clonidine hydrochloride over time was extremely good. Furthermore, the release of clonidine hydrochloride when applied as a patch was also good, and an effective plasma concentration sufficient for treatment was obtained. In addition, there was no adhesive residue after peeling and no rash on the skin surface to which it was applied.
実施例 ２
アクリル酸ノニルエステル55重量部、酢酸ビニ
ル25重量部、アクリル酸２−メトキシエチルエス
テル20重量部よりなる単量体混合物に対し、重合
開始剤としてBPO（過酸化ベンゾイル）を0.3重量
部用い、トルエ中にて65℃に昇温して重合させ、
８時間反応後、さらに75〜80℃に昇温して２時間
熟成して常温で粘着性を有する高分子物質のトル
エン溶液を得た。吸水率は8.9w／ｗ％／24hであ
つた。Example 2 0.3 parts by weight of BPO (benzoyl peroxide) as a polymerization initiator was added to a monomer mixture consisting of 55 parts by weight of acrylic acid nonyl ester, 25 parts by weight of vinyl acetate, and 20 parts by weight of acrylic acid 2-methoxyethyl ester. Polymerize by raising the temperature to 65℃ in toluene using
After reacting for 8 hours, the temperature was further raised to 75-80°C and aged for 2 hours to obtain a toluene solution of a polymeric substance that was sticky at room temperature. The water absorption rate was 8.9w/w%/24h.
次にこのようにして得られた高分子物質溶液
（該物質に対する硫酸アトロピンの飽和溶解量は
約3.1重量％である）に飽和溶解度以下に調製さ
れた酢酸アトロピンの水／メタノール（50／50重
量％）溶液を添加混合し、ポリエチレンフイルム
の表面に乾燥後の厚みが50μｍとなるように塗
布、乾燥させ、水溶性薬物含有の外用部材を得
た。本実施例で使用した硫酸アトロピンの添加量
は200μｇ／cm2（硫酸アトロピン含有量約５重量
％）となるように設定した。 Next, in the polymer substance solution obtained in this way (the saturated dissolution amount of atropine sulfate in the substance is about 3.1% by weight), atropine acetate was prepared to have a saturated solubility or less in water/methanol (50/50 by weight). %) solution was added and mixed, and coated on the surface of a polyethylene film so that the thickness after drying was 50 μm, and dried to obtain a water-soluble drug-containing external member. The amount of atropine sulfate used in this example was set to 200 μg/cm 2 (atropine sulfate content: approximately 5% by weight).
得られた外用部材中での硫酸アトロピンの溶解
性は良好であり、未溶解物や結晶の析出は観察さ
れず、経日変化における硫酸アトロピンの安定性
は良好であつた。更に貼着適用した場合の硫酸ア
トロピンの放出性も良好であり、治療に充分な有
効血漿中濃度の値が得られた。また剥離除去した
後の糊残り現象や適用皮膚面のカブレなどは全く
なかつた。 The solubility of atropine sulfate in the obtained external use member was good, no undissolved substances or precipitation of crystals were observed, and the stability of atropine sulfate over time was good. Furthermore, the release of atropine sulfate when applied as a patch was also good, and an effective plasma concentration value sufficient for treatment was obtained. In addition, there was no adhesive residue after peeling and no rash on the skin surface to which it was applied.
実施例 ３
アクリル酸ヘキシルエステル50重量部、メタア
クリル酸ドデシルエステル40重量部、アクリル酸
２−ヒドロキシエチルエステル10重量部よりなる
単量体混合物に対し、重合開始剤として
AIBN0.5重量部用い、酢酸エチル／エタノール
（69／31重量％）中にて沸点（71.8℃）での重合
を行ない、10時間反応させて常温で粘着性を有す
る高分子物質の酢酸エチル／エタノール溶液を得
た。Example 3 A monomer mixture consisting of 50 parts by weight of hexyl acrylate, 40 parts by weight of dodecyl methacrylate, and 10 parts by weight of 2-hydroxyethyl acrylate was added as a polymerization initiator.
Using 0.5 parts by weight of AIBN, polymerization was carried out at the boiling point (71.8°C) in ethyl acetate/ethanol (69/31% by weight), and the reaction was carried out for 10 hours to produce ethyl acetate/ethanol, a polymeric substance that is sticky at room temperature. An ethanol solution was obtained.
吸水率は3.7w／ｗ％／24hであつた。 The water absorption rate was 3.7w/w%/24h.
次にこのようにして得られた高分子物質溶液
（該物質に対するジクロフエナツクナトリウムの
飽和溶解量は約4.6重量％である）に飽和溶解度
以下に調製されたジクロフエナツク−ナトリウム
のエタノール溶液とジメチルスルホキシド10部を
添加混合し、不織布の表面に乾燥後の厚みが30μ
ｍとなるように塗布、乾燥させ、水溶性薬物含有
の外用部材を得た。本実施例で使用したジクロフ
エナツク−ナトリウムの添加量は400μｇ／cm2
（ジクロフエナツク−ナトリウム含有量約13重量
％）となるように設定した。 Next, in the polymer substance solution obtained in this manner (the saturated solubility of diclofenac sodium in the substance is about 4.6% by weight), an ethanol solution of diclofenac sodium prepared to have a saturation solubility or less and dimethyl sulfoxide were added. Add and mix 10 parts, and the thickness after drying is 30μ on the surface of the nonwoven fabric.
The mixture was applied and dried to obtain a water-soluble drug-containing member for external use. The amount of diclofenac sodium used in this example was 400 μg/cm 2
(diclofenac sodium content: approximately 13% by weight).
得られた外用部材中でのジクロフエナツク−ナ
トリウムの溶解性は良好であり、未溶解物や結晶
の析出は観察されず、経日変化におけるジクロフ
エナツク−ナトリウムの安定性は非常に良好であ
つた。更に貼着適用した場合のジクロフエナツク
−ナトリウムの放出性も良好であり、治療に充分
な有効血漿中濃度のレベルが維持できた。また剥
離除去した後の糊残り現象や適用皮膚面のカブレ
などは全くなかつた。 The solubility of diclofenac sodium in the obtained external use member was good, no undissolved substances or precipitation of crystals were observed, and the stability of diclofenac sodium over time was very good. Furthermore, the release of diclofenac sodium was good when applied as a patch, and an effective plasma concentration level sufficient for treatment could be maintained. In addition, there was no adhesive residue after peeling and no rash on the skin surface to which it was applied.
比較例 １〜３
各実施例において添加する水溶性薬物を水及
び／又はアルコール類以外の溶液又は、直接粉末
状態で添加混合し、水溶性薬物含有外用部材を得
た。Comparative Examples 1 to 3 The water-soluble drugs to be added in each example were added and mixed in a solution other than water and/or alcohol, or directly in the form of a powder, to obtain a water-soluble drug-containing external member.
この場合、安定性などは良好であるが薬物の溶
解性は著しく悪く、高分子物質中での結晶の析出
又は未溶解物が存在し放出性が悪く治療に有効な
血漿中濃度が得られなかつた。さらに貼着適用す
る際、皮膚接着性が悪く、貼着後端末ハガレや脱
落が生じた。 In this case, although the stability etc. of the drug is good, the solubility of the drug is extremely poor, and the presence of crystals precipitated or undissolved substances in the polymer substance results in poor release and makes it impossible to obtain a therapeutically effective plasma concentration. Ta. Furthermore, when applied by pasting, the skin adhesion was poor, and the ends peeled or fell off after being pasted.
Claims (1)
分とし、吸水率が25℃で10w／ｗ％／24h以下で
ある粘着性高分子物質の有機溶剤溶液に、水溶性
薬物の水及び／又はアルコール溶液を溶解してな
る混合物を担持体面に塗設してなることを特徴と
する外用部材の製法。 ２ 粘着性高分子物質の吸水率が25℃で10w／ｗ
％／24h以下である特許請求の範囲第１項記載の
外用部材の製法。[Scope of Claims] 1. A water-soluble drug is added to an organic solvent solution of an adhesive polymer substance containing a (meth)acrylic acid alkyl ester as a main component and having a water absorption rate of 10 w/w%/24 h or less at 25°C. and/or a method for producing an external member, characterized in that a mixture obtained by dissolving an alcohol solution is coated on the surface of a carrier. 2 Water absorption rate of adhesive polymer material is 10w/w at 25℃
%/24h or less, the method for producing an external member according to claim 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP58039516A JPS59164715A (en) | 1983-03-09 | 1983-03-09 | Manufacture of member for external use |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP58039516A JPS59164715A (en) | 1983-03-09 | 1983-03-09 | Manufacture of member for external use |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS59164715A JPS59164715A (en) | 1984-09-17 |
| JPH0530465B2 true JPH0530465B2 (en) | 1993-05-10 |
Family
ID=12555201
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP58039516A Granted JPS59164715A (en) | 1983-03-09 | 1983-03-09 | Manufacture of member for external use |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS59164715A (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS60228413A (en) * | 1984-04-27 | 1985-11-13 | Sekisui Chem Co Ltd | Tape or sheet for therapeutic use and its preparation |
| ATE493121T1 (en) | 1999-07-15 | 2011-01-15 | Hisamitsu Pharmaceutical Co | PERCUTANE ABSORBABLE PREPARATIONS |
| ATE464887T1 (en) * | 2001-05-31 | 2010-05-15 | Hisamitsu Pharmaceutical Co | PERCUTANEOUSLY ABSORBABLE PLASTERS |
| WO2004084946A1 (en) * | 2003-03-27 | 2004-10-07 | Cosmed. Co., Ltd. | Pressure-sensitive adhesive for percutaneous absorption, pressure-sensitive adhesive composition for percutaneous absorption, and medicinal preparation for percutaneous absorption |
| JP4920495B2 (en) * | 2007-05-28 | 2012-04-18 | 株式会社脇坂エンジニアリング | Resin sheet thermoforming equipment |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5711916A (en) * | 1980-06-26 | 1982-01-21 | Sekisui Chem Co Ltd | Adhesive tape or sheet for treatment |
| JPS5756424A (en) * | 1980-09-22 | 1982-04-05 | Nitto Electric Ind Co Ltd | Medical material for external use |
-
1983
- 1983-03-09 JP JP58039516A patent/JPS59164715A/en active Granted
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5711916A (en) * | 1980-06-26 | 1982-01-21 | Sekisui Chem Co Ltd | Adhesive tape or sheet for treatment |
| JPS5756424A (en) * | 1980-09-22 | 1982-04-05 | Nitto Electric Ind Co Ltd | Medical material for external use |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS59164715A (en) | 1984-09-17 |
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