JPS63313723A - External cataplasm - Google Patents
External cataplasmInfo
- Publication number
- JPS63313723A JPS63313723A JP14950987A JP14950987A JPS63313723A JP S63313723 A JPS63313723 A JP S63313723A JP 14950987 A JP14950987 A JP 14950987A JP 14950987 A JP14950987 A JP 14950987A JP S63313723 A JPS63313723 A JP S63313723A
- Authority
- JP
- Japan
- Prior art keywords
- drug
- propyl gallate
- sensitive adhesive
- pressure
- adhesive layer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 claims abstract description 82
- 239000003814 drug Substances 0.000 claims abstract description 71
- 239000010410 layer Substances 0.000 claims abstract description 64
- 239000000473 propyl gallate Substances 0.000 claims abstract description 41
- 229940075579 propyl gallate Drugs 0.000 claims abstract description 41
- 235000010388 propyl gallate Nutrition 0.000 claims abstract description 41
- 239000004820 Pressure-sensitive adhesive Substances 0.000 claims abstract description 34
- 238000009826 distribution Methods 0.000 claims abstract description 10
- 239000003381 stabilizer Substances 0.000 claims abstract description 5
- 229940079593 drug Drugs 0.000 claims description 66
- 229920000642 polymer Polymers 0.000 claims description 21
- 238000010030 laminating Methods 0.000 claims description 4
- 231100000475 skin irritation Toxicity 0.000 abstract description 14
- 206010040880 Skin irritation Diseases 0.000 abstract description 12
- 230000036556 skin irritation Effects 0.000 abstract description 12
- 229920000307 polymer substrate Polymers 0.000 abstract 4
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 22
- -1 2-ethylhexyl Chemical group 0.000 description 18
- 239000000463 material Substances 0.000 description 14
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
- 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 12
- 230000000052 comparative effect Effects 0.000 description 10
- 229920001577 copolymer Polymers 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 230000001070 adhesive effect Effects 0.000 description 9
- 230000000694 effects Effects 0.000 description 8
- 229920000728 polyester Polymers 0.000 description 8
- 239000000853 adhesive Substances 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 229960003878 haloperidol Drugs 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 230000000087 stabilizing effect Effects 0.000 description 6
- 238000001035 drying Methods 0.000 description 5
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 4
- 206010015150 Erythema Diseases 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical group CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 4
- 231100000321 erythema Toxicity 0.000 description 4
- 238000013508 migration Methods 0.000 description 4
- 230000005012 migration Effects 0.000 description 4
- 210000004400 mucous membrane Anatomy 0.000 description 4
- 239000004745 nonwoven fabric Substances 0.000 description 4
- 239000002985 plastic film Substances 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 238000012546 transfer Methods 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 239000004698 Polyethylene Substances 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 229920001971 elastomer Polymers 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 230000007794 irritation Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 229920006255 plastic film Polymers 0.000 description 3
- 229920000573 polyethylene Polymers 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
- 239000005060 rubber Substances 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- 230000000699 topical effect Effects 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
- DCRYNQTXGUTACA-UHFFFAOYSA-N 1-ethenylpiperazine Chemical compound C=CN1CCNCC1 DCRYNQTXGUTACA-UHFFFAOYSA-N 0.000 description 2
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-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
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 2
- PGMMQIGGQSIEGH-UHFFFAOYSA-N 2-ethenyl-1,3-oxazole Chemical compound C=CC1=NC=CO1 PGMMQIGGQSIEGH-UHFFFAOYSA-N 0.000 description 2
- KANZWHBYRHQMKZ-UHFFFAOYSA-N 2-ethenylpyrazine Chemical compound C=CC1=CN=CC=N1 KANZWHBYRHQMKZ-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
- RRHGJUQNOFWUDK-UHFFFAOYSA-N Isoprene Chemical compound CC(=C)C=C RRHGJUQNOFWUDK-UHFFFAOYSA-N 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- 206010033733 Papule Diseases 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 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 2
- 230000003078 antioxidant effect Effects 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
- 229960004022 clotrimazole Drugs 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000005038 ethylene vinyl acetate Substances 0.000 description 2
- FEBLZLNTKCEFIT-VSXGLTOVSA-N fluocinolone acetonide Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O FEBLZLNTKCEFIT-VSXGLTOVSA-N 0.000 description 2
- 239000011888 foil Substances 0.000 description 2
- LNTHITQWFMADLM-UHFFFAOYSA-N gallic acid Chemical compound OC(=O)C1=CC(O)=C(O)C(O)=C1 LNTHITQWFMADLM-UHFFFAOYSA-N 0.000 description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 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
- 239000011261 inert gas Substances 0.000 description 2
- 238000000691 measurement 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
- 231100000017 mucous membrane irritation Toxicity 0.000 description 2
- KJONHKAYOJNZEC-UHFFFAOYSA-N nitrazepam Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC(=O)CN=C1C1=CC=CC=C1 KJONHKAYOJNZEC-UHFFFAOYSA-N 0.000 description 2
- 229960001454 nitrazepam Drugs 0.000 description 2
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 2
- 239000002861 polymer material Substances 0.000 description 2
- 229920002689 polyvinyl acetate Polymers 0.000 description 2
- 239000011118 polyvinyl acetate Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 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
- PVHUJELLJLJGLN-INIZCTEOSA-N (S)-nitrendipine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC([N+]([O-])=O)=C1 PVHUJELLJLJGLN-INIZCTEOSA-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
- PBGPBHYPCGDFEZ-UHFFFAOYSA-N 1-ethenylpiperidin-2-one Chemical compound C=CN1CCCCC1=O PBGPBHYPCGDFEZ-UHFFFAOYSA-N 0.000 description 1
- CSCSROFYRUZJJH-UHFFFAOYSA-N 1-methoxyethane-1,2-diol Chemical compound COC(O)CO CSCSROFYRUZJJH-UHFFFAOYSA-N 0.000 description 1
- 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 1
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-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
- CMCLUJRFBZBVSW-UHFFFAOYSA-N 2-(2-hydroxyethoxy)-1-methoxyethanol;prop-2-enoic acid Chemical compound OC(=O)C=C.COC(O)COCCO CMCLUJRFBZBVSW-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
- XHZPRMZZQOIPDS-UHFFFAOYSA-N 2-Methyl-2-[(1-oxo-2-propenyl)amino]-1-propanesulfonic acid Chemical compound OS(=O)(=O)CC(C)(C)NC(=O)C=C XHZPRMZZQOIPDS-UHFFFAOYSA-N 0.000 description 1
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
- JDCUKFVNOWJNBU-UHFFFAOYSA-N 2-ethenyl-1,3-thiazole Chemical compound C=CC1=NC=CS1 JDCUKFVNOWJNBU-UHFFFAOYSA-N 0.000 description 1
- MZNSQRLUUXWLSB-UHFFFAOYSA-N 2-ethenyl-1h-pyrrole Chemical compound C=CC1=CC=CN1 MZNSQRLUUXWLSB-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
- 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
- HFCUBKYHMMPGBY-UHFFFAOYSA-N 2-methoxyethyl prop-2-enoate Chemical compound COCCOC(=O)C=C HFCUBKYHMMPGBY-UHFFFAOYSA-N 0.000 description 1
- 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
- KGIGUEBEKRSTEW-UHFFFAOYSA-N 2-vinylpyridine Chemical compound C=CC1=CC=CC=N1 KGIGUEBEKRSTEW-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
- 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
- BVPWJMCABCPUQY-UHFFFAOYSA-N 4-amino-5-chloro-2-methoxy-N-[1-(phenylmethyl)-4-piperidinyl]benzamide Chemical compound COC1=CC(N)=C(Cl)C=C1C(=O)NC1CCN(CC=2C=CC=CC=2)CC1 BVPWJMCABCPUQY-UHFFFAOYSA-N 0.000 description 1
- CFZDMXAOSDDDRT-UHFFFAOYSA-N 4-ethenylmorpholine Chemical compound C=CN1CCOCC1 CFZDMXAOSDDDRT-UHFFFAOYSA-N 0.000 description 1
- 229930000680 A04AD01 - Scopolamine Natural products 0.000 description 1
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 1
- 229930183010 Amphotericin Natural products 0.000 description 1
- QGGFZZLFKABGNL-UHFFFAOYSA-N Amphotericin A Natural products OC1C(N)C(O)C(C)OC1OC1C=CC=CC=CC=CCCC=CC=CC(C)C(O)C(C)C(C)OC(=O)CC(O)CC(O)CCC(O)C(O)CC(O)CC(O)(CC(O)C2C(O)=O)OC2C1 QGGFZZLFKABGNL-UHFFFAOYSA-N 0.000 description 1
- 239000004342 Benzoyl peroxide Substances 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 1
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 1
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-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
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- WJOHZNCJWYWUJD-IUGZLZTKSA-N Fluocinonide Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)COC(=O)C)[C@@]2(C)C[C@@H]1O WJOHZNCJWYWUJD-IUGZLZTKSA-N 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- PLDUPXSUYLZYBN-UHFFFAOYSA-N Fluphenazine Chemical compound C1CN(CCO)CCN1CCCN1C2=CC(C(F)(F)F)=CC=C2SC2=CC=CC=C21 PLDUPXSUYLZYBN-UHFFFAOYSA-N 0.000 description 1
- AGJUUQSLGVCRQA-SWOUQTJZSA-N Fungichromin Chemical compound CCCCC[C@@H](O)[C@@H]1[C@@H](O)C[C@@H](O)C[C@@H](O)C[C@@H](O)C[C@@H](O)C[C@@H](O)[C@@H](O)[C@H](O)\C(C)=C\C=C\C=C\C=C\C=C\[C@H](O)[C@@H](C)OC1=O AGJUUQSLGVCRQA-SWOUQTJZSA-N 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 244000043261 Hevea brasiliensis Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- STECJAGHUSJQJN-GAUPFVANSA-N Hyoscine Natural products C1([C@H](CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-GAUPFVANSA-N 0.000 description 1
- OMCPLEZZPVJJIS-UHFFFAOYSA-N Hypadil (TN) Chemical compound C1C(O[N+]([O-])=O)COC2=C1C=CC=C2OCC(O)CNC(C)C OMCPLEZZPVJJIS-UHFFFAOYSA-N 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
- STECJAGHUSJQJN-UHFFFAOYSA-N N-Methyl-scopolamin Natural products C1C(C2C3O2)N(C)C3CC1OC(=O)C(CO)C1=CC=CC=C1 STECJAGHUSJQJN-UHFFFAOYSA-N 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
- 239000004100 Oxytetracycline Substances 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- TZRXHJWUDPFEEY-UHFFFAOYSA-N Pentaerythritol Tetranitrate Chemical compound [O-][N+](=O)OCC(CO[N+]([O-])=O)(CO[N+]([O-])=O)CO[N+]([O-])=O TZRXHJWUDPFEEY-UHFFFAOYSA-N 0.000 description 1
- 239000000026 Pentaerythritol tetranitrate Substances 0.000 description 1
- AGJUUQSLGVCRQA-UHFFFAOYSA-N Pentamycin Natural products CCCCCC(O)C1C(O)CC(O)CC(O)CC(O)CC(O)CC(O)C(O)C(O)C(C)=CC=CC=CC=CC=CC(O)C(C)OC1=O AGJUUQSLGVCRQA-UHFFFAOYSA-N 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 239000005062 Polybutadiene Substances 0.000 description 1
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- GFNANZIMVAIWHM-OBYCQNJPSA-N triamcinolone 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]3CCC2=C1 GFNANZIMVAIWHM-OBYCQNJPSA-N 0.000 description 1
- 229960002117 triamcinolone acetonide Drugs 0.000 description 1
- YNDXUCZADRHECN-JNQJZLCISA-N triamcinolone acetonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O YNDXUCZADRHECN-JNQJZLCISA-N 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
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 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
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 230000002087 whitening effect Effects 0.000 description 1
- 239000002759 woven fabric Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- 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、没食子酸プロピルの添加によって薬物の安定
性を向上し、且つ、没食子酸プロピルの有する皮膚刺激
性を抑制した外用貼付剤に関するものである。DETAILED DESCRIPTION OF THE INVENTION (1) Field of Industrial Application The present invention relates to an external patch that improves drug stability by adding propyl gallate and suppresses the skin irritation properties of propyl gallate. It is something.
(b)従来の技術
薬物の経皮投与は、経口、注射、座薬などに比較して投
与時の煩わしさが少なく、又、肝臓代謝を受けないこと
、胃腸障害を生じないこと、薬物の放出速度が制限され
るので投与回数を減することがで鰺るなどの利点があり
、今後ますます多種の薬物の経皮投与が予想される。特
に、経皮投与法を利用したテープ製剤は薬理効果の持続
性、投薬量の調節の簡便さなどの点から注目されて(す
る。(b) Conventional technology Transdermal administration of drugs is less troublesome during administration than oral administration, injections, suppositories, etc., and also does not undergo liver metabolism, does not cause gastrointestinal disorders, and does not release drugs. Since the speed is limited, it has the advantage of reducing the number of administrations, and it is expected that more and more types of drugs will be administered transdermally in the future. In particular, tape preparations using transdermal administration are attracting attention because of their long-lasting pharmacological effects and ease of dosage adjustment.
しかし、薬物をテープ製剤にすることによって薬物自体
の安定性が損なわれることがしばしば見られ、そのため
に種々の安定化剤の検討がなされている。However, it is often seen that the stability of the drug itself is impaired when the drug is made into a tape formulation, and therefore various stabilizers have been investigated.
この安定化剤としては、薬物と直後反応しな(1(不活
性である)こと、毒性のないこと、比較的安価であるこ
となどが条件となる。The conditions for this stabilizer include that it does not react immediately with the drug (1 (being inactive), that it is non-toxic, and that it is relatively inexpensive).
没食子酸プロピルは、油脂酸化防止剤として一般的に知
られており、食用油、バター、リップスティック等に添
加されている。Propyl gallate is generally known as an oil and fat antioxidant and is added to edible oils, butter, lipsticks, and the like.
この没食子酸プロピルは強力な酸化防止効果を持つため
、経皮投与用の種々の薬物、特に酸化作用によって分解
を起こしやすい薬物に対しては強い安定化効果を示す。Since this propyl gallate has a strong antioxidant effect, it exhibits a strong stabilizing effect on various drugs for transdermal administration, especially drugs that are susceptible to decomposition due to oxidation.
(c)発明が解決しようとする問題点
没食子酸プロピルが、食品添加物として使用される場合
、毒性の点がら通常0.1重量%以下の濃度で用いられ
る。(c) Problems to be Solved by the Invention When propyl gallate is used as a food additive, it is usually used at a concentration of 0.1% by weight or less due to toxicity.
又、リップスティック、クリーム等の化粧品に添加して
使用される場合には、没食子酸の持つ皮膚刺激性の点か
ら1重量%以下で使用することが好ましいと報告されて
いる(JOUNAL OFAMERICAN C0
LLEGE OF TOXICOLOGY Vo
l、4、Number3.198523−57)。Furthermore, when it is added to cosmetics such as lipsticks and creams, it is reported that it is preferable to use it at 1% by weight or less due to the skin irritation of gallic acid (JOUNAL OFAMERICAN C0
LLEGE OF TOXICOLOGY Vo
1, 4, Number 3.198523-57).
一方、経皮投与用の薬物に添加する場合、1重量%以下
では、薬物安定化効果の発現に乏しく、添加濃度を上げ
る必要があるが、皮膚刺激性が増加するという欠点があ
った。On the other hand, when added to a drug for transdermal administration, if the amount is less than 1% by weight, the drug stabilizing effect is poor and it is necessary to increase the concentration, but this has the disadvantage of increasing skin irritation.
(d)問題点を解決するための手段
本発明者らは、この欠点を解決するため、鋭意検討を重
ねた結果、薬物の安定化に必要な没食子酸プロピルの濃
度を1%以上に保持しつつ、没食子酸プロピル由来の皮
膚刺激性を低減する方法を見い出だした。(d) Means for Solving the Problem In order to solve this drawback, the present inventors have conducted intensive studies and found that the concentration of propyl gallate necessary for stabilizing the drug was maintained at 1% or more. At the same time, we have discovered a method to reduce the skin irritation caused by propyl gallate.
つまり、高分子基材層中に経皮吸収可能な薬物とその薬
物を安定化させる没食子酸プロピルを添加し、これによ
って薬物の安定性を向上させ、且つこの高分子基材層の
皮膚面側に感圧接着剤層を積層することにより、没食子
酸プロピルの放出性を制御して当該没食子酸プロピルが
皮膚表面に到達することを抑制し、没食子酸プロピル由
来の皮膚刺激性の低減化を図ったものである。In other words, a transdermally absorbable drug and propyl gallate, which stabilizes the drug, are added to the polymer base layer, thereby improving the stability of the drug. By laminating a pressure-sensitive adhesive layer on the skin, the release properties of propyl gallate are controlled to prevent the propyl gallate from reaching the skin surface, thereby reducing the skin irritation derived from propyl gallate. It is something that
即ち、本発明の外用貼付剤は、支持体上に薬物及びその
薬物の安定化剤である没食子酸プロピルを含有する高分
子基材層および感圧接着剤層をこの順序で積層してなる
ことを特徴とするものである。That is, the external patch of the present invention is formed by laminating, in this order, a polymer base layer containing a drug and propyl gallate, which is a stabilizer for the drug, and a pressure-sensitive adhesive layer on a support. It is characterized by:
以下、本発明の詳細な説明する。The present invention will be explained in detail below.
本発明に用いる支持体としては、フィルム、シート、テ
ープ、布などの平面状物であれば任意のものが用いられ
るが、水分を実質的に透過させないか、或いは皮膚又は
粘膜にかぶれ、白化などの副作用をおこさせない程度に
水分の透過度合を調節、設計したポリオレフィン、ポリ
エステル、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質からなる各種の
プラスチックフィルム・シート、ゴム及び/又は合成樹
脂製の発泡シート、金属箔、織布、不織布とプラスチッ
クフィルムとのラミネート体などが好適に用いられる。As the support used in the present invention, any flat material such as a film, sheet, tape, or cloth can be used, but it does not substantially allow moisture to pass through or cause skin or mucous membrane irritation, whitening, etc. Various plastic films and sheets made of materials such as polyolefin, polyester, polyurethane, polyvinyl alcohol, polyvinylidene chloride, and polyamide, which are designed to adjust the degree of moisture permeability to a degree that does not cause side effects Foamed sheets, metal foils, woven fabrics, laminates of nonwoven fabrics and plastic films, etc. are suitably used.
本発明に用いられる高分子基材層としては、経皮吸収性
の薬物を含有させうるちのであれば限定されるものでは
ないが、特にポリ酢酸ビニル、エチレン−酢酸ビニル共
重合体、ポリビニルピロリドン−酢酸ビニル共重合体等
の酢酸ビニル単位を含有する高分子材料で形成された層
が柔軟性や薬物保持性の点で望ましい。The polymer base layer used in the present invention is not limited as long as it contains a transdermally absorbable drug, but in particular polyvinyl acetate, ethylene-vinyl acetate copolymer, polyvinylpyrrolidone - A layer formed of a polymeric material containing vinyl acetate units, such as a vinyl acetate copolymer, is desirable in terms of flexibility and drug retention.
又、本発明に用いられる感圧接着剤層としては、常温で
、感圧接着性を有するもので形成された層であればよく
、次に述べるような感圧性接着剤で形成された層が皮膚
接着性や薬物移行性の点で好適に用いられる。Further, the pressure-sensitive adhesive layer used in the present invention may be a layer formed of a material having pressure-sensitive adhesive properties at room temperature, and a layer formed of a pressure-sensitive adhesive as described below may be used. It is suitably used in terms of skin adhesion and drug transferability.
上記感圧性接着剤としては、親油性を有し、且つ常温で
感圧接着性を有するアクリル系粘着剤、例えば、(メタ
)アクリル酸ブチル、(メタ)アクリル酸ペンチル、(
メタ)アクリル酸ヘキシル、(メタ)アクリル酸2−エ
チルブチル、(メタ)アクリル酸ヘプチル、(メタ)ア
クリル酸インオクチル、(メタ)アクリル酸2−エチル
ヘキシル、(メタ)アクリル酸デシル、(メタ)アクリ
ル酸ドデシル、(メタ)アクリル酸トリデシルの如き(
メタ)アクリル酸エステルの単独重合体、或いはこれら
のエステル類と共重合可能なモノマーとの共重合体など
が挙げられる。The pressure-sensitive adhesive may be an acrylic adhesive that is lipophilic and has pressure-sensitive adhesive properties at room temperature, such as butyl (meth)acrylate, pentyl (meth)acrylate, (
Hexyl (meth)acrylate, 2-ethylbutyl (meth)acrylate, heptyl (meth)acrylate, inoctyl (meth)acrylate, 2-ethylhexyl (meth)acrylate, decyl (meth)acrylate, (meth)acrylate Such as dodecyl acid, tridecyl (meth)acrylate (
Examples include homopolymers of meth)acrylic acid esters, and copolymers of these esters with monomers copolymerizable.
上記共重合可能なモアマーとしては、例えば、(メタ)
アクリル酸、(無水)マレイン酸、(無水)イタコン酸
、7マール酸、(メタ)アクリル酸ヒドロキシエチル、
(メタ)アクリル酸ヒドロキシプロピル、(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(メタ)アクリルアミド、N−メチロール(メタ)
アクリルアミド、(メタ)アクリル酸アミノエチル、(
メタ)アクリル酸ジメチルアミノエチル、(メタ)アク
リル酸メトキンエチル、(メタ)アクリル酸エトキシエ
チル、(メタ)アクリル酸ブトキシエチル、(メタ)ア
クリル酸ヒドロフルフリル、(メタ)アクリル酸メトキ
シエチレングリコール、(メタ)アクリル酸メトキシジ
エチレングリコール、(メタ)アクリル酸メトキシポリ
エチレングリコール、(メタ)アクリル酸メトキシポリ
ブチレングリコール、スチレンスルホン酸、アリルスル
ホン酸、スルホプロピル(メタ)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、N−(メタ)アクリロイルアミノ
酸、アクリル酸のウレタン・尿素・インシアネートエス
テル、(メタ)アクリルニトリル、酢酸ビニル、プロピ
オン酸ビニル、バーサチック酸ビニル、スチレン、α−
メチルスチレン、ビニルピロリドン、ビニルピリジン、
ビニルピラジン、ビニルピペラジン、ビニルピペリドン
、ビニルピリミジン、ビニルピロール、ビニルオキサゾ
ール、ビニルピペラジンム、ビニルオキサゾール、ビニ
ルチアゾール、ビニルモルホリン、塩化ビニル、ビス(
N、N’−ジメチルアミノエチル)マレニートなどが挙
げられる。As the copolymerizable moamer, for example, (meth)
Acrylic acid, (anhydrous) maleic acid, (anhydrous) itaconic acid, hexamaric acid, hydroxyethyl (meth)acrylate,
Hydroxypropyl (meth)acrylate, (meth)acrylamide, trimethyl (meth)acrylamide, N-butyl (meth)acrylamide, N-methylol (meth)
Acrylamide, aminoethyl (meth)acrylate, (
Dimethylaminoethyl (meth)acrylate, methquinethyl (meth)acrylate, ethoxyethyl (meth)acrylate, butoxyethyl (meth)acrylate, hydrofurfuryl (meth)acrylate, methoxyethylene glycol (meth)acrylate, ( methoxydiethylene glycol acrylate, methoxypolyethylene glycol (meth)acrylate, methoxypolybutylene glycol (meth)acrylate, styrene sulfonic acid, allyl sulfonic acid, sulfopropyl (meth)acrylate, (meth)acryloyloxynaphthalene sulfonic acid, Acrylamidomethylpropanesulfonic acid, acryloyloxybenzenesulfonic acid, N-(meth)acryloyl amino acid, urethane/urea/incyanate ester of acrylic acid, (meth)acrylonitrile, vinyl acetate, vinyl propionate, vinyl versatate, styrene, α−
Methylstyrene, vinylpyrrolidone, vinylpyridine,
Vinylpyrazine, vinylpiperazine, vinylpiperidone, vinylpyrimidine, vinylpyrrole, vinyloxazole, vinylpiperazine, vinyloxazole, vinylthiazole, vinylmorpholine, vinyl chloride, bis(
Examples include N,N'-dimethylaminoethyl)malenate.
親油性を有し且つ常温で感圧接着性を有する他の高分子
としては、例えばシリコーン系粘着剤、ポリイソプレン
ゴム、ポリイソブチレンゴム、ポリブタジェン、スチレ
ン−ブタジェン(又はイソプレン)−スチレンブロック
共重合体ゴム、アクリルゴム等の合成ゴム系粘着剤或い
は天然ゴム系粘着剤などが挙げられる。Examples of other polymers that are lipophilic and have pressure-sensitive adhesive properties at room temperature include silicone adhesives, polyisoprene rubber, polyisobutylene rubber, polybutadiene, and styrene-butadiene (or isoprene)-styrene block copolymers. Examples include synthetic rubber adhesives such as rubber and acrylic rubber, and natural rubber adhesives.
そして、本発明の好ましい実施態様としでは、没食子酸
プロピルの感圧接着剤層に対する分配率が高分子基材層
に対する分配率より小さく−、その比率が0.3以下の
ものが望ましい。In a preferred embodiment of the present invention, the distribution ratio of propyl gallate to the pressure sensitive adhesive layer is smaller than the distribution ratio to the polymer base layer, and it is desirable that the ratio is 0.3 or less.
又、上記の高分子基材層と感圧接着剤層において、該高
分子基材層からの薬物の放出速度に対する没食子酸プロ
ピルの放出速度の比率が0.5以下のものが一層望まし
いのである。Further, in the polymer base layer and the pressure-sensitive adhesive layer, it is more desirable that the ratio of the release rate of propyl gallate to the release rate of the drug from the polymer base layer is 0.5 or less. .
この上)に没食子酸プロピルの放出速度や分配率を制御
することにより薬物の安定性を一層向上させると共に皮
膚又は粘膜の刺激を防止しうるのである。Moreover, by controlling the release rate and distribution rate of propyl gallate, it is possible to further improve the stability of the drug and prevent irritation of the skin or mucous membranes.
又、上記高分子基材層に溶解又は分散状態で含有される
薬物としては、上記の高分子基材層中で、酸化分解され
て含量低下を引く起こす薬物が好適であり、その薬物自
体は経皮・経粘膜吸収性のあるものである。Further, as the drug contained in the polymer base layer in a dissolved or dispersed state, it is preferable to use a drug that is oxidized and decomposed in the polymer base layer to cause a decrease in content, and the drug itself is It is absorbable through the skin and mucosa.
このような薬物としては、例えば以下に列挙するものが
挙げられる。Examples of such drugs include those listed below.
イ)フルチフステロイドj[=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、トリアムシノロン、トリアムシノロンア
セトニド、フルオシノ四ン、フルオシノロンアセトニド
、フルオシノ四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、
口)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、ジクロフェナックナトリウム、アルクロ7エナツ
ク、オキシ7エンブタゾン、7エエルプタゾン、イブプ
ロフェン、フルルビプロ7エン、サリチル酸、サリチル
酸メチル、!−メンt−ル、カン7アー、スリングツク
、トルメチンナトリウム、ナプロキセン、7エンプ7エ
ンなど、
ハ)催眠鎮静剤:例えばフェノバルビタール、アモパル
ビタール、シクa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、
二)精神安定剤:例えばフルフェナジン、テオリタシン
、ジアゼパム、フルジアゼパム、フルニトラゼバム、ハ
ロペリドール、クロルプロマジンなど、
ホ)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、プ7ラノロール、インデノロール、ニパジビン、ニ
モジピン、ロアニジキシン、ニトレンジピン、ニプラジ
ロール、ブクモロール、ニフェジピンなど、
ヘ)降圧利尿剤:例えばハイドロサイアザイド、ペンド
ロフルナサイアザイド、シクロベンチアザイドなど、
ト)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、
チ)麻酔剤二例えばリドカイン、塩酸ジブカイン、ペン
シカイン、アミ7安息香酸エチルなど、す)抗菌性物質
:例えば塩酸ペンザルフニウム、ニトロ7ラゾン、ナイ
スタチン、アセトスルファミン、クロトリマゾールなど
、
ヌ)抗真菌性物質:例えばペンタマイシン、アムホテリ
シンB1ビロールニドリン、クロトリマゾールなど、
ル)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7ヱロール、オフ)f−7シン、リ
ボフラビン酪酸エステルなど、ヲ)抗てんかん剤:例え
ばニトラゼパム、メプロパメート、クロナゼパムなど、
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、
力)抗ヒスタミン剤:例えば塩酸ジフェンヒドラミン、
クロルフェニラミン、ジフェニルイミグゾールなど、
ヨ)鎮咳剤:例えば臭化水素酸デキストロメトルファン
、硫酸テルブタソン、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、り)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、
し)抗菅剤:例えばドキセピン
ソ)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7ヱンブロジルなど、ツ)制吐剤、抗潰瘍
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、スコポラミン、臭化水素酸スコポラミン、5−
フルオロウラシル、メルカプトプリンなど、が挙げられ
る。b) Flutifosteroids [=e.g. hydrocortiscin, prednisolone, beclomethasone propionate,
flumethacin, triamcinolone, triamcinolone acetonide, fluocinolone, fluocinolone acetonide, fluocinolone acetonide acetate, clobetasol propionate, etc.) Analgesic anti-inflammatory agents: e.g. acetamino-7ene, mefenamic acid, flufenamic acid, indomethacin, diclo 7-enatsuc, diclofenac sodium, alcro-7enatsuc, oxy-7-enbutazone, 7-eluptazone, ibuprofen, flurbipro-7en, salicylic acid, methyl salicylate,! - Menthol, Can7ar, Slingtsk, Tolmetin Sodium, Naproxen, 7-en, etc.; c) Hypnosedatives: for example, phenobarbital, amoparbital, ciquaparbital, triapram, nitrazepam, lorazepam, haloperidol, etc.; ) Tranquilizers: e.g. fluphenazine, teolitasin, diazepam, fludiazepam, flunitrazebam, haloperidol, chlorpromazine, etc. e) Antihypertensive agents: e.g. clonidine, clonidine hydrochloride, etc.
pindolol, propranolol, propranolol hydrochloride, pr7ranolol, indenolol, nipazibine, nimodipine, roanidixine, nitrendipine, nipradilol, bucumolol, nifedipine, etc. f) Antihypertensive diuretics: e.g. hydrothiazide, pendroflunathiazide, cyclobenziazide, etc. ) Antibiotics: e.g. penicillin, tetracycline,
Oxytetracycline, 7-radiomycin sulfate, erythromycin, chloramphenicol, etc.; 1) Anesthetic agents, such as lidocaine, dibucaine hydrochloride, pensicaine, ethyl amyl-7 benzoate, etc.; Nystatin, acetosulfamine, clotrimazole, etc., n) Antifungal substances: e.g. pentamycin, amphotericin B1 virolnidoline, clotrimazole, etc. l) Vitamin preparations: e.g. vitamin A1 ergocalciferol, cholecalciferol, off) f) antiepileptic drugs such as nitrazepam, mepropamate, clonazepam, troglycol, isosorbide dinitrate, erythritol tetranitrate, pentaerythritol tetranitrate, propyl nitrate, etc.) Antihistamines: e.g. diphenhydramine hydrochloride,
chlorpheniramine, diphenylimiguzole, etc. ii) Antitussives: e.g. dextromethorphan hydrobromide, terbutasone sulfate, ephedrine, ephedrine hydrochloride, salbutamol sulfate, isoprotenol hydrochloride, isoprotenol sulfate, etc. ri) Sex hormones: e.g. propsterone , estradiol, etc., ii) Anti-surgical drugs: e.g. doxepinso) Cerebral circulation improving agents: e.g. videlgin, nilgott alkaloids, embrozil, etc., t) Anti-emetics, anti-ulcer agents: e.g. metoclopramide, clebopride, tonberitone, scopolamine, etc. Scopolamine hydrobromide, 5-
Examples include fluorouracil and mercaptopurine.
高分子材料を主体とする高分子基材と薬物との混合割合
は、高分子材料、薬物、添加剤の種類によっても異なる
が、高分子基材層全体に占める薬物の割合が0.01〜
30重量%、好ましくは0゜2〜20重量%の範囲内に
調整するのが良く、0゜01重量%未満では治療効果が
乏しく、一方30重量%を超えると治療効果に限界が生
じると共に結晶が析出して経皮吸収されにくい場合があ
り、経済的に不利である。The mixing ratio of the drug and the polymer base material, which is mainly composed of a polymer material, varies depending on the type of polymer material, drug, and additive, but the ratio of the drug to the entire polymer base layer is 0.01 to 0.01.
It is best to adjust the amount to 30% by weight, preferably within the range of 0.2 to 20% by weight.If it is less than 0.01% by weight, the therapeutic effect will be poor, while if it exceeds 30% by weight, there will be a limit to the therapeutic effect and crystallization will occur. may precipitate and be difficult to absorb through the skin, which is economically disadvantageous.
又、本発明において高分子基材層には没食子酸プロピル
が添加されるが、その濃度は薬物を安定化させうる量で
あればよく、薬物の種類によっても異なるが、組成物全
体に占める割合が1.0〜5重量%、好ましくは1.0
〜3重量%の範囲内に調整するのが望ましく、1.0重
量%未満では薬物の安定化に効果を示さない場合があり
、一方、5重量%を超えると安定化効果に差がなくなり
、皮膚刺激が発現するようになる恐れがあり好ましくな
い。In addition, in the present invention, propyl gallate is added to the polymer base layer, but its concentration may be any amount that can stabilize the drug, and although it varies depending on the type of drug, the proportion of propyl gallate in the entire composition may vary. is 1.0 to 5% by weight, preferably 1.0
It is desirable to adjust the amount within the range of ~3% by weight; if it is less than 1.0% by weight, it may not be effective in stabilizing the drug; on the other hand, if it exceeds 5% by weight, there is no difference in the stabilizing effect. This is not preferable as it may cause skin irritation.
なお、本発明の外用貼付剤は、支持体上に形成した高分
子基材層、該高分子基材層の露出面に積層された感圧接
着剤層を必須構成要素とするが、更に感圧接着剤層の露
出面に、剥離処理を施した可撓性を有する剥離フィルム
又は剥離紙を積層して当該感圧接着剤層表面を保護する
のが望ましい。The external patch of the present invention has a polymeric base layer formed on a support and a pressure-sensitive adhesive layer laminated on the exposed surface of the polymeric base layer as essential components. It is desirable to protect the surface of the pressure-sensitive adhesive layer by laminating a flexible release film or paper that has been subjected to a release treatment on the exposed surface of the pressure-sensitive adhesive layer.
そして、本発明の外用貼付剤は、全体を水分不透過性、
光不透過性の包装材、例えばアルミニウム箔とプラスチ
ックフィルムとのラミネートフィルムからできた袋に一
枚づつ又は一括して収納し、保存、流通に供するのが好
ましい。The external patch of the present invention is entirely water-impermeable,
It is preferable to store them one by one or all at once in a bag made of a light-impermeable packaging material, such as a laminate film of aluminum foil and plastic film, for storage and distribution.
(e)作用
本発明の外用貼付剤は、高分子基材層として高分子を主
体とする組成物に生理的活性を有する薬物と当該薬物を
安定化させる没食子酸プロピルを含有させ、これによっ
て、薬物の安定化を実現し、外用貼付剤の信頼性を向上
させる作用を有するのである。(e) Effect The external patch of the present invention contains a physiologically active drug and propyl gallate that stabilizes the drug in a polymer-based composition as a polymer base layer, thereby achieving the following effects: It has the effect of stabilizing drugs and improving the reliability of external patches.
又、本発明の外用貼付剤を皮膚又は粘膜に適用したとき
、没食子酸プロピルは感圧接着剤層中に移行されないか
又は、非常に低濃度の移行であるため、皮膚又は粘膜に
対する刺激は発現することがほとんどなく、薬物を安全
に生体内に投与しうる作用を有するのである。Furthermore, when the topical patch of the present invention is applied to the skin or mucous membranes, propyl gallate is not transferred into the pressure-sensitive adhesive layer or is transferred at a very low concentration, so irritation to the skin or mucous membranes does not occur. It has an effect that allows the drug to be safely administered into the body with little to no effect.
(f)実施例
以下、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 Hereinafter, the present invention will be explained in detail based on Examples, but the present invention is not limited thereto.
なお、文中において部及び%とあるのは重量部及び重量
%を示す。In addition, parts and % in the text indicate parts by weight and weight %.
実施例1
アクリル酸2−エチルヘキシルエステル55部、アクリ
ル酸メトキシエチルエステル30部、酢酸ビニル15部
、アゾビスイソビチロニトリル0゜3部を4つロフラス
コに仕込み、不活性ガス雰囲気下にて温度60〜63℃
に昇温しで重合反応を開始させ、これに酢酸エチル12
5部を滴下しながら反応温度を制御しつつ10時間反応
を続け、更に温度75〜80℃で2時間熟成して共重合
体溶液を得た。Example 1 55 parts of acrylic acid 2-ethylhexyl ester, 30 parts of acrylic acid methoxyethyl ester, 15 parts of vinyl acetate, and 0.3 parts of azobisisobityronitrile were charged into four flasks and heated under an inert gas atmosphere. 60-63℃
The polymerization reaction was started by raising the temperature to
The reaction was continued for 10 hours while controlling the reaction temperature while dropping 5 parts, and further aged at a temperature of 75 to 80°C for 2 hours to obtain a copolymer solution.
得られた共重合体溶液に、ジクロ7エナツクナトリウム
及びクエン酸を乾燥後の含有率がそれぞれ20%、4%
となるように添加混合し、ポリエステル製離型ライナー
上に薬物含有量が100μg/Cl112となるように
塗布、乾燥して感圧接着剤層を形成した。In the obtained copolymer solution, the contents of dichloro-7enac sodium and citric acid after drying were 20% and 4%, respectively.
The mixture was added and mixed so that the drug content was 100 μg/Cl112 on a polyester mold release liner, and dried to form a pressure-sensitive adhesive layer.
ポリ酢酸ビニル樹脂(数平均分子量 1800.20%
メタノール溶液)にジクロ7ヱナツクナトリウム、クエ
ン酸及び没食子酸プロピルを乾燥後の含有率がそれぞれ
20%、4%、3%となるように添加混合し、ポリエス
テル製離型ライナー上に薬物含有量が300μg/cl
o2となるように塗布、乾燥して高分子基材層を形成し
た。Polyvinyl acetate resin (number average molecular weight 1800.20%
Add and mix dichloro-7enac sodium, citric acid, and propyl gallate to a methanol solution) so that the dry contents are 20%, 4%, and 3%, respectively, and place the drug content on a polyester release liner. is 300μg/cl
o2 and dried to form a polymer base material layer.
この高分子基材層を支持体であるポリエチレンフィルム
に温度100℃で熱圧着し、これの高分子基材層の露出
面側から上記感圧接着剤層を貼着して本発明の外用貼付
剤を得た。This polymeric base material layer is thermocompression bonded to a polyethylene film as a support at a temperature of 100°C, and the above-mentioned pressure-sensitive adhesive layer is pasted from the exposed side of the polymeric base layer to form an external adhesive according to the present invention. obtained the drug.
この外用貼付剤中の没食子酸プロピル含量を後述する測
定法で測定したところ[注5)]、高分子基材層中2.
3%、感圧接着剤層中0.7%であった。When the propyl gallate content in this topical patch was measured using the measuring method described below [Note 5)], it was found that the content of propyl gallate in the polymer base layer was 2.
3%, and 0.7% in the pressure sensitive adhesive layer.
実施例2
アクリル酸2−エチルヘキシルエステル95部、アクリ
ル酸5部、過酸化ベンゾイル0.2部を4つロフラスコ
に仕込み、不活性〃ス雰囲気下にて温度62〜65℃に
昇温しで重合反応を開始させ、これに酢酸エチル125
部を滴下しながら反応温度を制御しつつ8時間反応を続
け、更に温度75〜80℃で2時間熟成して共重合体溶
液を得た。Example 2 95 parts of acrylic acid 2-ethylhexyl ester, 5 parts of acrylic acid, and 0.2 parts of benzoyl peroxide were charged into 4 flasks, and the temperature was raised to 62 to 65°C under an inert gas atmosphere to polymerize. Start the reaction and add 125% of ethyl acetate to it.
The reaction was continued for 8 hours while controlling the reaction temperature while adding the same amount dropwise, and further aged for 2 hours at a temperature of 75 to 80°C to obtain a copolymer solution.
得られた共重合体溶液にハロペリドールを乾燥後の含有
率が20%となるように添加混合しポリエステル離型ラ
イナー上に薬物含有量が100μg / c m 2と
なるように塗布、乾燥して感圧接着剤層を形成した。Haloperidol was added and mixed to the obtained copolymer solution so that the content after drying was 20%, and the mixture was coated on a polyester release liner so that the drug content was 100 μg/cm2, dried, and sensitized. A pressure adhesive layer was formed.
エチレン−酢酸ビニル共重合体(酢酸ビニル含量40%
)樹脂20部を含有するトルエン溶液にハロペリドール
と没食子酸プロピルを乾燥後の含有率がそれぞれ20%
、2%となるように添加混合し、ポリエステル製離型ラ
イナー上に薬物含有量が700μg/c、m2となるよ
うに塗布、乾燥して高分子基材層を形成した。Ethylene-vinyl acetate copolymer (vinyl acetate content 40%)
) Haloperidol and propyl gallate in a toluene solution containing 20 parts of resin, each with a dry content of 20%.
, 2%, and coated on a polyester mold release liner so that the drug content was 700 μg/c, m2, and dried to form a polymeric base material layer.
この高分子基材層を支持体である不織布にラミネートし
、これの高分子基材層の露出面側から上記感圧接着剤層
を貼着して本発明の外用貼付剤を得た。This polymeric base layer was laminated onto a nonwoven fabric as a support, and the above-mentioned pressure-sensitive adhesive layer was attached from the exposed side of the polymeric base layer to obtain an external patch of the present invention.
この外用貼付剤中の没食子酸プロピル含量を後述する測
定法で測定したところ[注5)]、高分子基材層中1.
6%、感圧接着剤層中0.4%であった。When the propyl gallate content in this topical patch was measured using the measurement method described below [Note 5)], it was found that the content of propyl gallate in the polymer base layer was 1.
6%, and 0.4% in the pressure sensitive adhesive layer.
比較例1
実施例1で得られた共重合体溶液に、ジクロ7エナツク
ナトリウム及びクエン酸を乾燥後の含有率がそれぞれ2
0%、4%となるように添加混合し、これをポリエステ
ル製離型ライナー上に薬物含有量が400IIg/cI
112となるように塗布、乾燥して感圧接着剤層を形成
し、該感圧接着剤層をポリエチレンフィルムに貼着して
なるものを用いた。Comparative Example 1 The copolymer solution obtained in Example 1 was added with dichloro-7enac sodium and citric acid at a dry content of 2% each.
The drug content was 400IIg/cI.
112 and dried to form a pressure-sensitive adhesive layer, and the pressure-sensitive adhesive layer was attached to a polyethylene film.
比較例2
実施例1で得られた共重合体溶液に、ジクロ7エナツク
ナトリウム、クエン酸及び没食子酸プロピルを乾燥後の
含有率がそれぞれ20%、4%、3%となるように添加
混合し、これをポリエステル製離型ライナー上に薬物含
有量が400μg/Cm2となるように塗布、乾燥して
感圧接着剤層を形成し、該感圧接着剤層をポリエチレン
フィルムに貼着してなるものを用いた。Comparative Example 2 To the copolymer solution obtained in Example 1, dichloro-7enac sodium, citric acid, and propyl gallate were added and mixed so that the contents after drying were 20%, 4%, and 3%, respectively. This was applied onto a polyester mold release liner so that the drug content was 400 μg/cm2, dried to form a pressure-sensitive adhesive layer, and the pressure-sensitive adhesive layer was attached to a polyethylene film. I used something like
比較例3
実施例2で得られた共重合体溶液にハロペリドールを乾
燥後の含有率が20%となるように添加混合し、これを
ポリエステル製離型ライナー上に薬物含有量が800μ
g/cm2となるように塗布、乾燥して感圧接着剤層を
形成し、該感圧接着剤層を不織布に貼着してなるものを
用いた。Comparative Example 3 Haloperidol was added and mixed to the copolymer solution obtained in Example 2 so that the content after drying was 20%, and this was placed on a polyester release liner with a drug content of 800μ.
g/cm 2 and dried to form a pressure-sensitive adhesive layer, and the pressure-sensitive adhesive layer was attached to a nonwoven fabric.
比較例4
実施例2で得られた共重合体溶液にハロペリドール及び
没食子酸プロピルを乾燥後の含有率がそれぞれ20%、
2%となるように添加混合し、これをポリエステル製離
型ライナー上に薬物含有量が800μg/cI112と
なるように塗布、乾燥して感圧接着剤層を形成し、該感
圧接着剤層を不織布に貼着しでなるものを用いた。Comparative Example 4 The content of haloperidol and propyl gallate in the copolymer solution obtained in Example 2 after drying was 20%, respectively.
2%, and coated on a polyester mold release liner so that the drug content was 800 μg/cI112, and dried to form a pressure-sensitive adhesive layer. A material made by pasting on a non-woven fabric was used.
及び4は実施例2にそれぞれ対応している。and 4 correspond to Example 2, respectively.
各実施例及び各比較例にて得られた外用貼付剤について
、薬物の経日安定性、薬物の皮膚移行性、皮膚接着性、
適用皮膚面の刺激試験を行い、それらの結果を第1表に
示す。Regarding the external patches obtained in each example and each comparative example, the stability of the drug over time, the skin migration property of the drug, the skin adhesion property,
An irritation test was conducted on the applied skin surface, and the results are shown in Table 1.
第1表 第1表に示す各特性の測定方法は以下の通りである。Table 1 The method for measuring each characteristic shown in Table 1 is as follows.
注1)経口安定性
縦5ea+、横3cI11に裁断した各試料片を温度4
0℃にて3ケ月及び6ケ月保存し、その後、その各試料
片をメタノール抽出し、高速液体クロマトグラフィーに
て定量した。Note 1) Oral stability Each sample piece cut into length 5ea+ and width 3cI11 was heated to temperature 4.
The samples were stored at 0° C. for 3 and 6 months, and then each sample piece was extracted with methanol and quantified using high performance liquid chromatography.
○・・・残存率95%以上、Δ・・・残存率90%以上
95%未満、×・・・残存率90%未満。○...Residual rate 95% or more, Δ...Residual rate 90% or more but less than 95%, ×...Residual rate less than 90%.
注2)薬物皮膚移行性
縦5 am、 li 3 en+に裁断した各試料片を
人体皮膚表面に24時間貼付した後剥離し、この各試料
片中に残存する薬物をメタノール抽出し、高速液体クロ
マトグラフィーにて定量した。Note 2) Drug skin migration: Each sample piece cut vertically into 5 am and li 3 en+ was applied to the human skin surface for 24 hours and then peeled off. The drug remaining in each sample piece was extracted with methanol and subjected to high performance liquid chromatography. It was quantified using graphics.
この試料片の初期含有量から皮膚面への移行量を算出し
、比較例1及び比較例2中のそれぞれの薬物の移行量を
それぞれ1.0としてその比率で示した。The transfer amount to the skin surface was calculated from the initial content of this sample piece, and the transfer amount of each drug in Comparative Example 1 and Comparative Example 2 was set as 1.0, and the ratio was expressed.
注3)皮膚接着性
縦5cm5横30I11に裁断した各試料片を人体皮膚
表面に24時間貼付後、皮膚への接着状態を目視にて判
別した。Note 3) Skin adhesion Each sample piece cut into 5 cm x 30 x 11 pieces was applied to the human skin surface for 24 hours, and the state of adhesion to the skin was visually determined.
O・・・接着面積90%以上、Δ・・・接着面積50%
以上90%未満、×・・・接着面積50%未満。O...Adhesive area 90% or more, Δ...Adhesive area 50%
or more, less than 90%, ×... less than 50% of adhesive area.
注4)皮膚刺激性
各試料片(3cmφ)をヒト背中に24時間貼付し、剥
離1時間後の皮膚状態を目視にて判別し、下記の如く点
数を付け、10名の平均値にて判定した。Note 4) Skin irritation Each sample piece (3 cm φ) was pasted on the back of a person for 24 hours, and the skin condition was visually determined 1 hour after it was removed. Scores were given as shown below, and the evaluation was based on the average value of 10 people. did.
○・・・平均i、o、1未満、Δ・・・平均1.0点以
上2.0点未満、×・・・平均2,0点以上。○...Average i, o less than 1, Δ...Average 1.0 points or more and less than 2.0 points, ×...Average 2.0 points or more.
0点・・・無反応
0.5点・・・わずかな紅斑
1.0点・・・明らかな紅斑
2.0点・・・紅斑と丘疹或いは浮腫
3.0点・・・紅斑と浮腫と丘疹或いは小水痘4.0点
・・・大水痘
注5)没食子酸プロピルの基材層間での分配率測定法
実施例1,2に示した薬物を含有する高分子基材層に同
じ厚さの、薬物お上び没食子酸プロピルおよびその他の
添加剤を含有しない感圧接着剤層を貼着した試料を、室
温、40℃、70℃で薬物および没食子酸プロピルの移
動が平衡状態に達するまで保存した。0 points...no reaction 0.5 points...slight erythema 1.0 points...obvious erythema 2.0 points...erythema and papules or edema 3.0 points...erythema and edema Papules or small varicella 4.0 points...major varicella Note 5) Measurement method of distribution ratio between base material layers of propyl gallate The polymer base material layer containing the drug shown in Examples 1 and 2 has the same thickness. Samples with a pressure-sensitive adhesive layer that does not contain the drug, propyl gallate, and other additives were incubated at room temperature, 40°C, and 70°C until the migration of the drug and propyl gallate reached an equilibrium state. saved.
この試料を、縦5cm、横3cmに裁断したのち、高分
子基材層と感圧接着剤層を分離し、メタノール抽出後、
高速液体クロマト7ラフイーにて高分子基材層および感
圧接着剤層に含有される没食子酸プロピルの含量を定量
して分配率を求めた。After cutting this sample into 5 cm long and 3 cm wide, the polymer base material layer and pressure sensitive adhesive layer were separated, and after methanol extraction,
The content of propyl gallate contained in the polymer base material layer and the pressure-sensitive adhesive layer was determined using high performance liquid chromatography 7 Roughy to determine the distribution ratio.
第1表より、実施例品は薬物の経口安定性が良好であり
、又、薬物の皮膚移行性及び皮膚接着性も良好である上
、皮膚刺激性が極力制御されていることが認められる。From Table 1, it can be seen that the Example products have good oral stability of the drug, good skin transferability and skin adhesion of the drug, and skin irritation is controlled as much as possible.
これに対して比較例1及び比較例2では薬物の経口安定
性が悪く、保存によって薬物の分解が認められ、保存性
の点で問題が認められる。On the other hand, in Comparative Example 1 and Comparative Example 2, the oral stability of the drug was poor, and decomposition of the drug was observed during storage, resulting in problems in terms of storage stability.
又、比較例3では薬物の安定性、薬物の皮膚移行性及び
皮膚接着性は良好であるが、皮膚刺激性が強く使用者に
苦痛を与える恐れがあり、又、比較例4では薬物の経日
安定性に問題があり、しかも皮膚刺激性の点でも問題が
あり、使用者によっては苦痛を与えることが予想される
。In addition, in Comparative Example 3, the drug stability, skin migration and skin adhesion of the drug are good, but the skin irritation is strong and may cause pain to the user. It has problems in terms of daily stability and skin irritation, and is expected to cause pain to some users.
(g)発明の効果
本発明の外用貼付剤は、上記構成を有し、高分子基材層
に生理的活性を有する薬物と没食子酸プロピルを含有さ
せて薬物の長期安定性を実現するのであり、しかもこの
高分子基材層にはその皮膚或いは粘膜の貼着面側に、薬
物の移行をほとんど制限せず、且つ皮膚や粘膜の刺激の
原因となる没食子酸プロピルの放出を極力制御・抑制す
る感圧粘着剤層を設けてなるのであり、これによって、
没食子酸プロピルの皮膚への移行に伴う皮膚刺激性が解
消されると共に薬物を効率よく生体内に吸収させること
がで外るのであり、その結果、何人も安心して使用しう
る効果を有するのである。(g) Effects of the Invention The external patch of the present invention has the above-mentioned structure, and achieves long-term stability of the drug by containing a physiologically active drug and propyl gallate in the polymeric base layer. Moreover, this polymeric base material layer hardly restricts the transfer of the drug to the skin or mucous membrane surface, and also controls and suppresses the release of propyl gallate, which causes skin and mucous membrane irritation, as much as possible. A pressure-sensitive adhesive layer is provided, which allows for
The skin irritation caused by the transfer of propyl gallate to the skin is eliminated, and the drug is efficiently absorbed into the body, resulting in an effect that can be used by many people with peace of mind. .
Claims (2)
食子酸プロピルを含有する高分子基材層および感圧接着
剤層をこの順序で積層してなることを特徴とする外用貼
付剤。(1) An external patch characterized by laminating a drug and a polymeric base layer containing propyl gallate, which is a stabilizer for the drug, and a pressure-sensitive adhesive layer on a support in this order. .
は高分子基材層に対する分配率より小さく、その比率は
0.3以下である特許請求の範囲第1項に記載の外用貼
付剤。(2) The external patch according to claim 1, wherein the distribution ratio of propyl gallate to the pressure-sensitive adhesive layer is smaller than the distribution ratio to the polymer base layer, and the ratio is 0.3 or less.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP14950987A JPS63313723A (en) | 1987-06-16 | 1987-06-16 | External cataplasm |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP14950987A JPS63313723A (en) | 1987-06-16 | 1987-06-16 | External cataplasm |
Publications (1)
Publication Number | Publication Date |
---|---|
JPS63313723A true JPS63313723A (en) | 1988-12-21 |
Family
ID=15476694
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP14950987A Pending JPS63313723A (en) | 1987-06-16 | 1987-06-16 | External cataplasm |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPS63313723A (en) |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH02202813A (en) * | 1989-01-31 | 1990-08-10 | Sekisui Chem Co Ltd | Percutaneous absorbing preparation |
EP0904778A1 (en) * | 1997-09-05 | 1999-03-31 | Nitto Denko Corporation | Stabilized percutaneous absorption preparation |
JP2002128701A (en) * | 2000-10-26 | 2002-05-09 | Sankyo Co Ltd | External antiphologistic and analgesic agent composition |
JP2008101029A (en) * | 2008-01-17 | 2008-05-01 | Nitto Denko Corp | Percutaneous absorption type preparation |
JP2008101027A (en) * | 2008-01-17 | 2008-05-01 | Nitto Denko Corp | Percutaneous absorption type preparation |
JP2008101028A (en) * | 2008-01-17 | 2008-05-01 | Nitto Denko Corp | Percutaneous absorption type preparation |
JP2009173679A (en) * | 2001-03-07 | 2009-08-06 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system for administration of partial dopamine-d2 agonist |
US9731490B2 (en) | 2008-10-02 | 2017-08-15 | Mylan Inc. | Method for making a multilayer adhesive laminate |
JP2021522240A (en) * | 2018-04-25 | 2021-08-30 | シンケイ セラピューティクス リミテッド ライアビリティ カンパニー | Tetrabenazine transdermal delivery device |
-
1987
- 1987-06-16 JP JP14950987A patent/JPS63313723A/en active Pending
Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH02202813A (en) * | 1989-01-31 | 1990-08-10 | Sekisui Chem Co Ltd | Percutaneous absorbing preparation |
EP0904778A1 (en) * | 1997-09-05 | 1999-03-31 | Nitto Denko Corporation | Stabilized percutaneous absorption preparation |
JP2002128701A (en) * | 2000-10-26 | 2002-05-09 | Sankyo Co Ltd | External antiphologistic and analgesic agent composition |
JP2009173679A (en) * | 2001-03-07 | 2009-08-06 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system for administration of partial dopamine-d2 agonist |
JP2008101029A (en) * | 2008-01-17 | 2008-05-01 | Nitto Denko Corp | Percutaneous absorption type preparation |
JP2008101027A (en) * | 2008-01-17 | 2008-05-01 | Nitto Denko Corp | Percutaneous absorption type preparation |
JP2008101028A (en) * | 2008-01-17 | 2008-05-01 | Nitto Denko Corp | Percutaneous absorption type preparation |
US9731490B2 (en) | 2008-10-02 | 2017-08-15 | Mylan Inc. | Method for making a multilayer adhesive laminate |
US10272656B2 (en) | 2008-10-02 | 2019-04-30 | Mylan Inc. | Method for making a multilayer adhesive laminate |
JP2021522240A (en) * | 2018-04-25 | 2021-08-30 | シンケイ セラピューティクス リミテッド ライアビリティ カンパニー | Tetrabenazine transdermal delivery device |
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