JPS6248644B2 - - Google Patents
Info
- Publication number
- JPS6248644B2 JPS6248644B2 JP8803980A JP8803980A JPS6248644B2 JP S6248644 B2 JPS6248644 B2 JP S6248644B2 JP 8803980 A JP8803980 A JP 8803980A JP 8803980 A JP8803980 A JP 8803980A JP S6248644 B2 JPS6248644 B2 JP S6248644B2
- Authority
- JP
- Japan
- Prior art keywords
- drug
- water
- monomer
- patch
- polymerization
- 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
Links
- 239000003814 drug Substances 0.000 claims description 41
- 229940079593 drug Drugs 0.000 claims description 40
- 239000000203 mixture Substances 0.000 claims description 38
- 239000000178 monomer Substances 0.000 claims description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
- 239000002998 adhesive polymer Substances 0.000 claims description 11
- 238000006116 polymerization reaction Methods 0.000 claims description 10
- 239000012790 adhesive layer Substances 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 9
- 239000003995 emulsifying agent Substances 0.000 claims description 5
- 230000005865 ionizing radiation Effects 0.000 claims description 4
- 238000003756 stirring Methods 0.000 claims description 4
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 claims description 3
- 239000000654 additive Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 3
- 229920002554 vinyl polymer Polymers 0.000 claims description 3
- 229920003169 water-soluble polymer Polymers 0.000 claims description 3
- 239000003505 polymerization initiator Substances 0.000 claims description 2
- 230000001678 irradiating effect Effects 0.000 claims 1
- 239000012071 phase Substances 0.000 description 13
- -1 azo compound Chemical class 0.000 description 11
- 239000000839 emulsion Substances 0.000 description 7
- 229920000642 polymer Polymers 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 238000012662 bulk polymerization Methods 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 239000003242 anti bacterial agent Substances 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 4
- 102000011782 Keratins Human genes 0.000 description 3
- 108010076876 Keratins Proteins 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
- BLFLLBZGZJTVJG-UHFFFAOYSA-N benzocaine Chemical compound CCOC(=O)C1=CC=C(N)C=C1 BLFLLBZGZJTVJG-UHFFFAOYSA-N 0.000 description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 210000000434 stratum corneum Anatomy 0.000 description 3
- 229920002818 (Hydroxyethyl)methacrylate Polymers 0.000 description 2
- 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 2
- LVYLCBNXHHHPSB-UHFFFAOYSA-N 2-hydroxyethyl salicylate Chemical compound OCCOC(=O)C1=CC=CC=C1O LVYLCBNXHHHPSB-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-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
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- WOBHKFSMXKNTIM-UHFFFAOYSA-N Hydroxyethyl methacrylate Chemical compound CC(=C)C(=O)OCCO WOBHKFSMXKNTIM-UHFFFAOYSA-N 0.000 description 2
- 239000004820 Pressure-sensitive adhesive Substances 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000000853 adhesive Substances 0.000 description 2
- 230000001070 adhesive effect Effects 0.000 description 2
- POJWUDADGALRAB-UHFFFAOYSA-N allantoin Chemical compound NC(=O)NC1NC(=O)NC1=O POJWUDADGALRAB-UHFFFAOYSA-N 0.000 description 2
- 229940035674 anesthetics Drugs 0.000 description 2
- 239000000730 antalgic agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 229940121375 antifungal agent Drugs 0.000 description 2
- 239000000739 antihistaminic agent Substances 0.000 description 2
- 229940125715 antihistaminic agent Drugs 0.000 description 2
- 229940030600 antihypertensive agent Drugs 0.000 description 2
- 239000002220 antihypertensive agent Substances 0.000 description 2
- 229960005274 benzocaine Drugs 0.000 description 2
- KVYGGMBOZFWZBQ-UHFFFAOYSA-N benzyl nicotinate Chemical compound C=1C=CN=CC=1C(=O)OCC1=CC=CC=C1 KVYGGMBOZFWZBQ-UHFFFAOYSA-N 0.000 description 2
- 239000003576 central nervous system agent Substances 0.000 description 2
- 229940125693 central nervous system agent Drugs 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 239000003246 corticosteroid Substances 0.000 description 2
- 229960001334 corticosteroids Drugs 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- MMXKVMNBHPAILY-UHFFFAOYSA-N ethyl laurate Chemical compound CCCCCCCCCCCC(=O)OCC MMXKVMNBHPAILY-UHFFFAOYSA-N 0.000 description 2
- 239000003193 general anesthetic agent Substances 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
- MOYKHGMNXAOIAT-JGWLITMVSA-N isosorbide dinitrate Chemical compound [O-][N+](=O)O[C@H]1CO[C@@H]2[C@H](O[N+](=O)[O-])CO[C@@H]21 MOYKHGMNXAOIAT-JGWLITMVSA-N 0.000 description 2
- 229960000201 isosorbide dinitrate Drugs 0.000 description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 230000035699 permeability Effects 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
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 2
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 229960004889 salicylic acid Drugs 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000013269 sustained drug release Methods 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 229940124549 vasodilator Drugs 0.000 description 2
- 239000003071 vasodilator agent Substances 0.000 description 2
- DNXIKVLOVZVMQF-UHFFFAOYSA-N (3beta,16beta,17alpha,18beta,20alpha)-17-hydroxy-11-methoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]-yohimban-16-carboxylic acid, methyl ester Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(C(=O)OC)C(O)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 DNXIKVLOVZVMQF-UHFFFAOYSA-N 0.000 description 1
- YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 description 1
- NJPQAIBZIHNJDO-UHFFFAOYSA-N 1-dodecylpyrrolidin-2-one Chemical compound CCCCCCCCCCCCN1CCCC1=O NJPQAIBZIHNJDO-UHFFFAOYSA-N 0.000 description 1
- OSSNTDFYBPYIEC-UHFFFAOYSA-N 1-ethenylimidazole Chemical compound C=CN1C=CN=C1 OSSNTDFYBPYIEC-UHFFFAOYSA-N 0.000 description 1
- PVVATGNFHKTPTA-UHFFFAOYSA-N 1-methylsulfinyloctane Chemical compound CCCCCCCCS(C)=O PVVATGNFHKTPTA-UHFFFAOYSA-N 0.000 description 1
- FRPZMMHWLSIFAZ-UHFFFAOYSA-N 10-undecenoic acid Chemical compound OC(=O)CCCCCCCCC=C FRPZMMHWLSIFAZ-UHFFFAOYSA-N 0.000 description 1
- VFFDVELHRCMPLY-UHFFFAOYSA-N 12-methyltridecan-1-amine Chemical compound CC(C)CCCCCCCCCCCN VFFDVELHRCMPLY-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
- 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
- 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
- OMIGHNLMNHATMP-UHFFFAOYSA-N 2-hydroxyethyl prop-2-enoate Chemical compound OCCOC(=O)C=C OMIGHNLMNHATMP-UHFFFAOYSA-N 0.000 description 1
- CPHGOBGXZQKCKI-UHFFFAOYSA-N 4,5-diphenyl-1h-imidazole Chemical compound N1C=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 CPHGOBGXZQKCKI-UHFFFAOYSA-N 0.000 description 1
- HBTAOSGHCXUEKI-UHFFFAOYSA-N 4-chloro-n,n-dimethyl-3-nitrobenzenesulfonamide Chemical compound CN(C)S(=O)(=O)C1=CC=C(Cl)C([N+]([O-])=O)=C1 HBTAOSGHCXUEKI-UHFFFAOYSA-N 0.000 description 1
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- XZIIFPSPUDAGJM-UHFFFAOYSA-N 6-chloro-2-n,2-n-diethylpyrimidine-2,4-diamine Chemical compound CCN(CC)C1=NC(N)=CC(Cl)=N1 XZIIFPSPUDAGJM-UHFFFAOYSA-N 0.000 description 1
- DXPPIEDUBFUSEZ-UHFFFAOYSA-N 6-methylheptyl prop-2-enoate Chemical compound CC(C)CCCCCOC(=O)C=C DXPPIEDUBFUSEZ-UHFFFAOYSA-N 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- POJWUDADGALRAB-PVQJCKRUSA-N Allantoin Natural products NC(=O)N[C@@H]1NC(=O)NC1=O POJWUDADGALRAB-PVQJCKRUSA-N 0.000 description 1
- 229930003347 Atropine Natural products 0.000 description 1
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-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
- POPFMWWJOGLOIF-XWCQMRHXSA-N Flurandrenolide Chemical compound C1([C@@H](F)C2)=CC(=O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O POPFMWWJOGLOIF-XWCQMRHXSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 1
- 239000004166 Lanolin Substances 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
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-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
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 1
- 239000000006 Nitroglycerin Substances 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
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- LCQMZZCPPSWADO-UHFFFAOYSA-N Reserpilin Natural products COC(=O)C1COCC2CN3CCc4c([nH]c5cc(OC)c(OC)cc45)C3CC12 LCQMZZCPPSWADO-UHFFFAOYSA-N 0.000 description 1
- QEVHRUUCFGRFIF-SFWBKIHZSA-N Reserpine Natural products O=C(OC)[C@@H]1[C@H](OC)[C@H](OC(=O)c2cc(OC)c(OC)c(OC)c2)C[C@H]2[C@@H]1C[C@H]1N(C2)CCc2c3c([nH]c12)cc(OC)cc3 QEVHRUUCFGRFIF-SFWBKIHZSA-N 0.000 description 1
- SKZKKFZAGNVIMN-UHFFFAOYSA-N Salicilamide Chemical compound NC(=O)C1=CC=CC=C1O SKZKKFZAGNVIMN-UHFFFAOYSA-N 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- ABBQHOQBGMUPJH-UHFFFAOYSA-M Sodium salicylate Chemical compound [Na+].OC1=CC=CC=C1C([O-])=O ABBQHOQBGMUPJH-UHFFFAOYSA-M 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
- 229940022663 acetate Drugs 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 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 1
- 229960000458 allantoin Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000002921 anti-spasmodic effect Effects 0.000 description 1
- 229940125681 anticonvulsant agent Drugs 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 229940125708 antidiabetic agent Drugs 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940124575 antispasmodic agent Drugs 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 1
- 229960000396 atropine Drugs 0.000 description 1
- 229940125717 barbiturate Drugs 0.000 description 1
- NBMKJKDGKREAPL-DVTGEIKXSA-N beclomethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O NBMKJKDGKREAPL-DVTGEIKXSA-N 0.000 description 1
- 229940092705 beclomethasone Drugs 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- 229950004580 benzyl nicotinate Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 229960002537 betamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-DVTGEIKXSA-N betamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-DVTGEIKXSA-N 0.000 description 1
- KHAVLLBUVKBTBG-UHFFFAOYSA-N caproleic acid Natural products OC(=O)CCCCCCCC=C KHAVLLBUVKBTBG-UHFFFAOYSA-N 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 229940106164 cephalexin Drugs 0.000 description 1
- ZAIPMKNFIOOWCQ-UEKVPHQBSA-N cephalexin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=CC=C1 ZAIPMKNFIOOWCQ-UEKVPHQBSA-N 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229960005091 chloramphenicol Drugs 0.000 description 1
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 1
- ZPEIMTDSQAKGNT-UHFFFAOYSA-N chlorpromazine Chemical compound C1=C(Cl)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 ZPEIMTDSQAKGNT-UHFFFAOYSA-N 0.000 description 1
- 229960001076 chlorpromazine Drugs 0.000 description 1
- 229960002896 clonidine Drugs 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 229960003529 diazepam Drugs 0.000 description 1
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 229940031578 diisopropyl adipate Drugs 0.000 description 1
- 229960000525 diphenhydramine hydrochloride Drugs 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 230000005183 environmental health Effects 0.000 description 1
- 229960003276 erythromycin Drugs 0.000 description 1
- UIWXSTHGICQLQT-UHFFFAOYSA-N ethenyl propanoate Chemical compound CCC(=O)OC=C UIWXSTHGICQLQT-UHFFFAOYSA-N 0.000 description 1
- 229960004511 fludroxycortide Drugs 0.000 description 1
- 229960001347 fluocinolone acetonide Drugs 0.000 description 1
- 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 1
- 229960000785 fluocinonide Drugs 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- PGBHMTALBVVCIT-VCIWKGPPSA-N framycetin Chemical compound 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 PGBHMTALBVVCIT-VCIWKGPPSA-N 0.000 description 1
- 238000010528 free radical solution polymerization reaction Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229960003711 glyceryl trinitrate Drugs 0.000 description 1
- 229960002389 glycol salicylate Drugs 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 239000003163 gonadal steroid hormone Substances 0.000 description 1
- 230000020169 heat generation Effects 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 229960004194 lidocaine Drugs 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- FQPSGWSUVKBHSU-UHFFFAOYSA-N methacrylamide Chemical compound CC(=C)C(N)=O FQPSGWSUVKBHSU-UHFFFAOYSA-N 0.000 description 1
- LZCOQTDXKCNBEE-IKIFYQGPSA-N methscopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3[N+]([C@H](C2)[C@@H]2[C@H]3O2)(C)C)=CC=CC=C1 LZCOQTDXKCNBEE-IKIFYQGPSA-N 0.000 description 1
- 229960001047 methyl salicylate Drugs 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
- 229960001383 methylscopolamine Drugs 0.000 description 1
- 229940053050 neomycin sulfate Drugs 0.000 description 1
- 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 1
- 229960001454 nitrazepam Drugs 0.000 description 1
- IAIWVQXQOWNYOU-FPYGCLRLSA-N nitrofural Chemical compound NC(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 IAIWVQXQOWNYOU-FPYGCLRLSA-N 0.000 description 1
- 229960001907 nitrofurazone Drugs 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000004745 nonwoven fabric Substances 0.000 description 1
- 229960000988 nystatin Drugs 0.000 description 1
- VQOXZBDYSJBXMA-NQTDYLQESA-N nystatin A1 Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/CC/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 VQOXZBDYSJBXMA-NQTDYLQESA-N 0.000 description 1
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical class CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-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
- 235000014593 oils and fats Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 150000001451 organic peroxides Chemical class 0.000 description 1
- 229960000625 oxytetracycline Drugs 0.000 description 1
- IWVCMVBTMGNXQD-PXOLEDIWSA-N oxytetracycline Chemical compound C1=CC=C2[C@](O)(C)[C@H]3[C@H](O)[C@H]4[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O IWVCMVBTMGNXQD-PXOLEDIWSA-N 0.000 description 1
- 235000019366 oxytetracycline Nutrition 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical class OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000002685 polymerization catalyst Substances 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 229960003147 reserpine Drugs 0.000 description 1
- BJOIZNZVOZKDIG-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C([C]5C=CC(OC)=CC5=N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 BJOIZNZVOZKDIG-MDEJGZGSSA-N 0.000 description 1
- MDMGHDFNKNZPAU-UHFFFAOYSA-N roserpine Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(OC(C)=O)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 MDMGHDFNKNZPAU-UHFFFAOYSA-N 0.000 description 1
- 229960000581 salicylamide Drugs 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229960004025 sodium salicylate Drugs 0.000 description 1
- 229940035044 sorbitan monolaurate Drugs 0.000 description 1
- 229940031439 squalene Drugs 0.000 description 1
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 1
- IWVCMVBTMGNXQD-UHFFFAOYSA-N terramycin dehydrate Natural products C1=CC=C2C(O)(C)C3C(O)C4C(N(C)C)C(O)=C(C(N)=O)C(=O)C4(O)C(O)=C3C(=O)C2=C1O IWVCMVBTMGNXQD-UHFFFAOYSA-N 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 229960002703 undecylenic acid Drugs 0.000 description 1
- 229940045136 urea Drugs 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 239000002759 woven fabric Substances 0.000 description 1
Description
【発明の詳細な説明】
この発明は身体の疾患部の治療ないし循環系へ
薬を投与するために身体に直接貼り付ける貼付剤
の製造方法に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing a patch that is applied directly to the body for treating diseased areas of the body or for administering medicine to the circulatory system.
従来、この種の貼付剤はプラスチツクフイルム
などの支持体上に薬剤を混入させた通常溶液状の
粘着剤組成物を塗布乾燥して薬剤含有の粘着剤層
を設けた構成からなつている。貼け付け使用に際
しては粘着剤層の粘着性を利用して身体面にその
まま貼り付け、身体の疾患部の治療ないし循環系
へ薬剤を投与させる。ところがこのような貼付剤
によると一般に薬剤の徐放性に劣り、薬効が短時
間に消失する欠点があつた。 Conventionally, this type of patch has a structure in which a pressure-sensitive adhesive composition containing a drug, usually in the form of a solution, is coated on a support such as a plastic film and dried to provide a drug-containing pressure-sensitive adhesive layer. When used as a patch, the adhesive layer is used to apply the adhesive to the body surface to treat diseased areas of the body or administer drugs to the circulatory system. However, such patches generally have the disadvantage that they have poor sustained drug release properties and their medicinal efficacy disappears in a short period of time.
この発明は上記の欠点が解消された貼付剤の製
造法を提供せんとするもので、以下図面を参考に
して説明する。 The present invention aims to provide a method for producing a patch that eliminates the above-mentioned drawbacks, and will be described below with reference to the drawings.
第１図および第２図はこの発明法により製造さ
れた貼付剤の一例を示したものであつて、１はプ
ラスチツクフイルム、不織布、織布、金属とプラ
スチツクとの複合フイルム、不連続発泡シートの
如き支持体、２は架橋結合が導入された親油性の
粘着性ポリマーからなる連続相２Ａと水または水
に水溶性ポリマーなどを含ませた水系混合物から
なる分散相２Ｂとで構成され、かつ主として連続
相２Ａ中に薬剤を均一に溶解ないし一部分散させ
てなる薬剤含有の粘着剤層である。 Figures 1 and 2 show an example of a patch manufactured by the method of the present invention, in which 1 is a patch made of plastic film, nonwoven fabric, woven fabric, composite film of metal and plastic, and discontinuous foam sheet. The support 2 is composed of a continuous phase 2A made of a cross-linked lipophilic adhesive polymer and a dispersed phase 2B made of water or an aqueous mixture of water containing a water-soluble polymer, etc. This is a drug-containing adhesive layer formed by uniformly dissolving or partially dispersing a drug in the continuous phase 2A.
この発明においてはこのような薬剤含有の粘着
剤層２を形成するために、まず特定の粘着性ポリ
マー組成物を調製する。すなわち上記の組成物は
モノマーを含む粘着性ポリマー組成物であり、次
の方法で調製される。 In this invention, in order to form such a drug-containing adhesive layer 2, a specific adhesive polymer composition is first prepared. That is, the above composition is an adhesive polymer composition containing monomers, and is prepared by the following method.
粘着性ポリマーを与えるためのモノマーとして
とくに（メタ）アクリル酸エステルないしビニル
系モノマーと極性モノマーとからなる親油性のモ
ノマー混合物が用いられる。ここでビニル系モノ
マーとしてはスチレン、酢酸ビニル、プロピオン
酸ビニル、ビニルピロリドン、ビニルイミダゾー
ルなどがあり、また極性モノマーとしては（メ
タ）アクリル酸、無水マレイン酸、イタコン酸、
アクリルアミド、メタクリルアミド、ヒドロキシ
エチルアクリレート、ヒドロキシエチルメタクリ
レート、などの官能基含有モノマーが挙げられ
る。 In particular, a lipophilic monomer mixture consisting of a (meth)acrylic acid ester or vinyl monomer and a polar monomer is used as the monomer for providing the adhesive polymer. Vinyl monomers include styrene, vinyl acetate, vinyl propionate, vinylpyrrolidone, vinylimidazole, etc., and polar monomers include (meth)acrylic acid, maleic anhydride, itaconic acid,
Examples include functional group-containing monomers such as acrylamide, methacrylamide, hydroxyethyl acrylate, and hydroxyethyl methacrylate.
この発明においては上記のモノマー混合物を重
合させる際に有機溶剤や水媒体を使用せずモノマ
ーだけの塊状重合法を採用する。塊状重合のため
の開始剤としては一般の有機過酸化物、アゾ系化
合物などの重合触媒が用いられる。一方かかる塊
状重合は発熱的に進行するが、この重合系内に一
部未反応モノマーが残存する段階で重合反応を停
止させる。 In this invention, when polymerizing the above-mentioned monomer mixture, a bulk polymerization method using only the monomers is adopted without using an organic solvent or an aqueous medium. As an initiator for bulk polymerization, a general polymerization catalyst such as an organic peroxide or an azo compound is used. On the other hand, such bulk polymerization proceeds exothermically, but the polymerization reaction is stopped at a stage when some unreacted monomer remains in the polymerization system.
この停止のためにとくに水または水にポリアク
リル酸塩、ポリビニルアルコールなどの水溶性ポ
リマーや低級アルコールその他の添加剤を含ませ
た水系混合物が用いられる。つまり重合発熱段階
で上記水または水系混合物を重合系内に徐々に添
加して抜熱する。この添加量は一般に仕込みモノ
マー100重量部に対して最終的に10〜700重量部と
なるように設定される。 For this purpose, water or an aqueous mixture containing water-soluble polymers such as polyacrylates and polyvinyl alcohol, lower alcohols, and other additives is used. That is, during the exothermic stage of polymerization, the water or aqueous mixture is gradually added into the polymerization system to remove heat. The amount added is generally set so that the final amount is 10 to 700 parts by weight per 100 parts by weight of the monomer charged.
このようにして冷却された水または水系混合物
を含む組成物は、これが粘度が低すぎる場合など
に必要に応じてソルビタンモノラウレート、ポリ
オキシエチレンソルビタンモノステアレートなど
の乳化剤が添加され、次いでデイスパーやアジホ
モミクサーなどの手段によつて強力撹拌される。 The composition containing water or an aqueous mixture cooled in this way is treated with an emulsifier such as sorbitan monolaurate or polyoxyethylene sorbitan monostearate, if necessary, if the viscosity is too low, and then a dispersant. The mixture is vigorously stirred using a homomixer or other means.
かくして得られる粘着性ポリマー組成物は、親
油性の未反応モノマーおよびポリマーからなる油
相成分に水または水系混合物からなる水相成分が
乳化分散されたＷ／Ｏ型エマルジヨンであり、こ
のエマルジヨンの安定性は乳化剤の種類や量、水
または水系混合物の添加量などを設定することに
よつて確保される。 The adhesive polymer composition thus obtained is a W/O emulsion in which an aqueous phase component consisting of water or an aqueous mixture is emulsified and dispersed in an oil phase component consisting of lipophilic unreacted monomers and polymers, and the stability of this emulsion is The properties are ensured by setting the type and amount of emulsifier, the amount of water or an aqueous mixture added, etc.
次にこの発明においては上記粘着性ポリマー組
成物に薬剤を含ませ、これを支持体１に直接塗工
するか、あるいは一旦剥離ライナーに塗設した後
支持体１に転着させ、次いで上記直接塗工ないし
転着後にあるいは転着前に電離性放射線を照射し
て重合架橋処理する。 Next, in the present invention, the adhesive polymer composition is impregnated with a drug and applied directly to the support 1, or once applied to a release liner and then transferred to the support 1, and then directly applied to the support 1. After or before coating or transfer, ionizing radiation is irradiated to perform polymerization and crosslinking treatment.
このような重合架橋処理によつて、前記油相成
分が薬剤を含んだ状態で完全にポリマー化しかつ
ポリマー相互が架橋された連続相２Ａを構成する
一方、この連続相２Ａ中に水粒子ないし水系混合
物粒子が分散相２Ｂとして安定に保持された前記
構成の粘着剤層２が形成される。 Through such polymerization and crosslinking treatment, the oil phase component is completely polymerized in a state containing the drug and constitutes a continuous phase 2A in which the polymers are crosslinked with each other. The adhesive layer 2 having the above structure is formed in which the mixture particles are stably held as the dispersed phase 2B.
なおＷ／Ｏ型エマルジヨンからなる粘着性ポリ
マー組成物に配合する薬剤は油相成分に溶解する
ものであつて、連続相２Ａを形成したときにこの
相２Ａ内を拡散移動して身体面に移着ないし吸収
させることができるものであり、たとえばコルチ
コステロイド類、麻酔剤、抗ヒスタミン剤、抗菌
性物質、抗真菌剤、鎮痛消炎剤、角質軟化剤、ビ
タミン剤、けいれん止めなど、また全身性薬とし
ての降圧剤、抗生物質、中枢神経作用剤、血管拡
張剤、鎮けい剤、鎮静剤、性ホルモン剤、抗糖尿
剤などがある。これら薬剤はその種類に応じて目
的とする治療ないし投与効果を得るための適量が
選択される。 Note that the drug blended into the adhesive polymer composition consisting of a W/O emulsion is dissolved in the oil phase component, and when the continuous phase 2A is formed, it diffuses within this phase 2A and transfers to the body surface. Substances that can be worn or absorbed, such as corticosteroids, anesthetics, antihistamines, antibacterial agents, antifungals, analgesics, emollients, vitamins, anticonvulsants, and as systemic drugs. These include antihypertensive agents, antibiotics, central nervous system agents, vasodilators, antispasmodics, sedatives, sex hormones, and antidiabetic agents. An appropriate amount of these drugs is selected to obtain the desired treatment or administration effect depending on the type of drug.
コルチコステロイド類としては酢酸プレゾニゾ
ロン、プレゾニゾロン、酢酸ヒドロコルチド、デ
キサメタゾン、フルオシノロンアセトニド、ベタ
メサゾン、プロピオン酸ベクロメタゾン、フルド
ロキシコルチド、フルオシノニドなどが挙げられ
る。麻酔剤としてはベンゾカイン、リドカイン、
アミノ安息香酸エチルなどが、抗ヒスタミン剤と
しては塩酸ジフエンヒドラミン、塩酸イソサイペ
ンジル、ジフエニールイミダゾールなどが、抗菌
性物質としては塩化ベンザルコニウム、ニトロフ
ラゾンなどが、抗真菌剤としてはナイスタチン、
ウンデシレン酸などが、鎮痛消炎剤としてはイン
ドメタシン、サリチル酸メチル、サリチル酸グリ
コール、サリチル酸アミド、サリチル酸ナトリウ
ムなどが、それぞれ挙げられる。 Examples of corticosteroids include prezonisolone acetate, presonisolone, hydrocortide acetate, dexamethasone, fluocinolone acetonide, betamethasone, beclomethasone propionate, fludroxycortide, fluocinonide, and the like. Anesthetics include benzocaine, lidocaine,
Ethyl aminobenzoate, etc.; antihistamines include diphenhydramine hydrochloride, isocypenzyl hydrochloride, diphenylimidazole, etc.; antibacterial agents include benzalkonium chloride and nitrofurazone; antifungal agents include nystatin,
Examples of analgesic and anti-inflammatory agents include undecylenic acid, and indomethacin, methyl salicylate, glycol salicylate, salicylic acid amide, and sodium salicylate.
また角質軟化剤、ビタミン剤およびけいれん止
めとしてサリチル酸、ビタミンＡ、アトロピン、
メススコポールアミンブロマイドなどを挙げるこ
とができる。さらに全身性薬としてのレセルピ
ン、クロニジンなどの降圧剤、エリスロマイシ
ン、クロラムフエニコール、セフアレキシン、テ
トラサイクリン、ネオマイシン硫酸塩、オキシテ
トラサイクリン、ペニシリンなどの抗生物質、バ
ルビツレート、ジアゼパム、ニトラゼパム、クロ
ルプロマジンなどの中枢神経作用剤、ニトログリ
セリン、イソソルバイドジナイトレートなどの血
管拡張剤などが挙げられる。 In addition, salicylic acid, vitamin A, atropine,
Examples include methscopolamine bromide. In addition, systemic drugs such as antihypertensive agents such as reserpine and clonidine, antibiotics such as erythromycin, chloramphenicol, cephalexin, tetracycline, neomycin sulfate, oxytetracycline, and penicillin, and central nervous system agents such as barbiturates, diazepam, nitrazepam, and chlorpromazine and vasodilators such as nitroglycerin and isosorbide dinitrate.
また上記の薬剤とともにこの薬剤の放出を促進
する放出補助物質を前記Ｗ／Ｏ型エマルジヨンに
混入させてもよく、またエマルジヨンの安定性を
阻害することのない各種添加剤を添加することも
できる。 In addition to the above-mentioned drug, a release auxiliary substance that promotes the release of the drug may be mixed into the W/O emulsion, and various additives that do not impede the stability of the emulsion may also be added.
上記の放出補助物質は単純には身体面に対する
薬剤の放出を促進するものと定義することができ
るが、これには粘着剤層内での薬剤の溶解性や拡
散性を良くする機能を有するもの、また角質の保
水能、角質軟化性、角質浸透性（ルーズ化）、浸
透助剤や毛孔開孔剤としての働らき、皮膚の界面
状態を変える機能の如き経皮吸収性を良くする機
能を有するもの、さらに上記の両機能を併有しあ
るいはこれら機能に加えて薬剤の薬効をより高く
する薬効促進の機能をも有しているものなどが広
く包含される。 The above-mentioned release auxiliary substances can be simply defined as substances that promote the release of drugs to the body surface, but they also include substances that have the function of improving the solubility and diffusibility of drugs within the adhesive layer. It also has functions that improve transdermal absorption, such as the water retention capacity of the stratum corneum, keratin softening properties, stratum corneum permeability (loosening), functions as a penetration aid and pore opening agent, and the function of changing the skin interface condition. This includes a wide range of drugs, including those that have both of the above-mentioned functions, or those that have, in addition to these functions, a function of promoting drug efficacy to further enhance the drug's efficacy.
これら放出補助物質の具体例としては、たとえ
ばジエチレングリコール、プロピレングリコー
ル、ポリエチレングリコールの如きグリコール類
（主に薬剤溶解性）、オリーブ油、スクアレン、ラ
ノリンなどの油脂類（主に薬剤拡散性）、尿素、
アラントインの如き尿素誘導体（主に角質の保水
能）、ジメチルデシルホスキサイド、メチルオク
チルスルホキサイド、ジメチルラウリルアミド、
ドデシルピロリドン、イソソルビトール、ジメチ
ルアセトアミド、ジメチルスルフオキシド、ジメ
チルホルムアミドなどの極性溶剤（主に角質浸透
性）、サリチル酸（主に角質軟化性）、アミノ酸
（主に浸透助剤）、ニコチン酸ベンジル（主に毛孔
開孔剤）、ラウリル硫酸ソーダ（主に皮膚の界面
状態を変える機能）、サロコール（経皮吸収性良
好な薬剤と併用）などが挙げられる。その他ジイ
ソプロピルアジペート、フタル酸エステル、ジエ
チルセバケートの如き可塑剤、流動パラフインの
如き炭化水素類、各種乳化剤、エトキシ化ステア
リルアルコール、グリセリンの高級エステルエー
テル、ミリスチン酸イソプロピル、ラウリン酸エ
チルなどを挙げることができる。 Specific examples of these release auxiliary substances include glycols (mainly drug-soluble) such as diethylene glycol, propylene glycol, and polyethylene glycol, oils and fats (mainly drug-diffusing) such as olive oil, squalene, and lanolin, urea,
Urea derivatives such as allantoin (mainly for the water retention capacity of stratum corneum), dimethyldecyl phosoxide, methyl octyl sulfoxide, dimethyl laurylamide,
Polar solvents such as dodecylpyrrolidone, isosorbitol, dimethylacetamide, dimethyl sulfoxide, and dimethylformamide (mainly keratin permeability), salicylic acid (mainly keratin softening), amino acids (mainly penetration aid), benzyl nicotinate ( These include (mainly pore openers), sodium lauryl sulfate (mainly functions to change the skin interface condition), and Sarokol (used in combination with drugs that have good transdermal absorption). Other examples include plasticizers such as diisopropyl adipate, phthalate esters, and diethyl sebacate, hydrocarbons such as liquid paraffin, various emulsifiers, ethoxylated stearyl alcohol, higher ester ethers of glycerin, isopropyl myristate, and ethyl laurate. can.
このようにして製造される前記構成の貼付剤に
よれば、粘着剤層２の粘着性を利用して身体面に
直接貼り付けることができ、この貼り付けによつ
て連続相２Ａの薬剤がこの層２Ａ内部を拡散移動
して身体面に移着ないし吸収される。このとき層
２内部には薬剤が拡散移動しにくい分散相２Ｂが
存在し、かつ連続層２Ａ自体が全体的に架橋され
たより緻密な層とされていることによつて、適度
な拡散速度が得られ、薬効の持続性に好結果が持
たらされる。 According to the patch having the above structure manufactured in this way, it can be directly applied to the body surface by utilizing the adhesiveness of the adhesive layer 2, and by this application, the drug of the continuous phase 2A can be applied to the body surface. It diffuses inside the layer 2A and is transferred or absorbed onto the body surface. At this time, the dispersed phase 2B in which the drug is difficult to diffuse and move exists inside the layer 2, and the continuous layer 2A itself is a denser layer that is crosslinked as a whole, so that an appropriate diffusion rate can be achieved. This results in better sustainability of drug efficacy.
以上詳述したとおり、この発明法はモノマーを
含む特定の粘着性ポリマー組成物を調製しこれに
薬剤を含ませた状態で電離性放射線を照射し重合
架橋させることにより薬剤含有の粘着剤層を形成
することおよび上記組成物の調製に際し、特定の
モノマー混合物を塊状重合させる一方、未反応の
モノマーを含む重合初期ないし中期の段階で水ま
たは水系混合物を添加して抜熱した後強力撹拌す
ることを特徴とするものである。 As detailed above, this invention method prepares a specific adhesive polymer composition containing a monomer, and irradiates the composition with ionizing radiation to polymerize and crosslink the composition, thereby forming a drug-containing adhesive layer. When forming and preparing the above composition, while bulk polymerizing a specific monomer mixture, water or an aqueous mixture is added at an early to middle stage of polymerization containing unreacted monomers, and after removing heat, stirring is performed vigorously. It is characterized by:
この方法によれば第一に薬効の持続性にすぐれ
る貼付剤を製造できるという効果が得られる。ま
た第二に塊状重合法を採用したことによつて有機
溶剤などを用いる場合の環境衛生上の問題やコス
ト上の問題を回避できる一方、塊状重合法の欠点
とされる重合発熱の問題を重合反応途中で水また
は水系混合物を徐々に添加することによつて解消
することができる。加えて上記添加後引き続き強
力撹拌することによつて薬効の持続性を図るに適
したＷ／Ｏ型エマルジヨンからなる粘着性ポリマ
ー組成物を製造できるから、薬剤含有の粘着剤組
成物の製造が極めて容易となる。 This method has the first effect of producing a patch with excellent long-lasting medicinal efficacy. Secondly, by adopting the bulk polymerization method, it is possible to avoid environmental health problems and cost problems when using organic solvents, etc., while the problem of polymerization heat generation, which is a drawback of the bulk polymerization method, can be avoided. This can be solved by gradually adding water or an aqueous mixture during the reaction. In addition, by continuing to stir vigorously after the above addition, it is possible to produce an adhesive polymer composition consisting of a W/O emulsion suitable for maintaining the medicinal effect, making it extremely easy to produce an adhesive composition containing a drug. It becomes easier.
以下にこの発明の実施例を記載する。以下にお
いて部および％とあるはそれぞれ重量部および重
量％を意味するものとする。 Examples of this invention will be described below. In the following, parts and % mean parts by weight and % by weight, respectively.
実施例
イソオクチルアクリレート80％、酢酸ビニル18
％およびヒドロキシエチルメタクリート２％から
なる親油性モノマー混合物を、重合開始剤として
アゾビスイソブチロニトリルを用いて窒素気流中
60℃で反応させ、約８分後から徐々に水を添加し
添加開始後約15分後で重合系内を室温まで冷却し
た。このときの水全添加量は仕込みモノマー混合
物100部に対して80部であつた。その後系内に乳
化剤としてポリオキシエチレンソルビタンモノス
テアレートを５部添加した後、デイスパーにより
1000〜1300rpmで強力撹拌してＷ／Ｏ型エマルジ
ヨンからなる粘着性ポリマー組成物を調製した。
この組成物の油相成分には未反応モノマーが含ま
れていた。Example 80% isooctyl acrylate, vinyl acetate 18
% and 2% hydroxyethyl methacrylate in a nitrogen stream using azobisisobutyronitrile as a polymerization initiator.
The reaction was carried out at 60°C, water was gradually added after about 8 minutes, and about 15 minutes after the start of addition, the inside of the polymerization system was cooled to room temperature. The total amount of water added at this time was 80 parts per 100 parts of the charged monomer mixture. After that, after adding 5 parts of polyoxyethylene sorbitan monostearate as an emulsifier into the system,
A sticky polymer composition consisting of a W/O emulsion was prepared by vigorous stirring at 1000 to 1300 rpm.
The oil phase component of this composition contained unreacted monomer.
このポリマー組成物にイソソルバイドジナイト
レートを２部添加して混合した後、80μ厚のポリ
エチレンシート上に50μ厚みに塗工し、次いで電
離性放射線を5Mrad照射し重合架橋させることに
より、この発明の貼付剤をつくつた。 After adding 2 parts of isosorbide dinitrate to this polymer composition and mixing it, it was coated to a thickness of 50μ on an 80μ thick polyethylene sheet, and then 5 Mrad of ionizing radiation was irradiated to polymerize and crosslink it. Created an invented patch.
上記実施例の貼付剤の薬剤の徐放性を調べるた
めに下記の水中放出性試験を行なつた。 In order to investigate the sustained drug release properties of the patches of the above examples, the following water release test was conducted.
＜水中放出性試験＞
貼付剤から４×４cmの試験片を作成し、これを
200mlの水中（30℃）に浸漬し、所定時間毎に薬
剤の放出量を調べた。なお薬剤の定量は放出水溶
液１mlに対し、ヘキサン５mlで薬剤を抽出し、ガ
スクロマトグラフイー装置により行なつた。<Water release test> Create a 4 x 4 cm test piece from the patch, and
It was immersed in 200 ml of water (30°C), and the amount of drug released was examined at predetermined intervals. The quantitative determination of the drug was performed by extracting the drug with 5 ml of hexane per 1 ml of the released aqueous solution and using a gas chromatography device.
第３図は上記の試験結果を示したもので、図中
曲線―１ａが実施例の結果、曲線―１ｂが比較例
の結果である。ここで比較例とは実施例に記載の
モノマー混合物から常法により溶液重合してつく
られたポリマー溶液に実施例±に記載の薬剤をポ
リマー100部に対して２部配合してなる組成物を
実施例に記載の支持体上に塗着させてなる従来の
貼付剤である。 FIG. 3 shows the above test results, in which curve 1a is the result of the example and curve 1b is the result of the comparative example. Here, the comparative example is a composition obtained by adding 2 parts of the drug described in Example ± to 100 parts of the polymer to a polymer solution prepared by solution polymerization from the monomer mixture described in the Example by a conventional method. This is a conventional patch formed by coating on the support described in the Examples.
上記の図から明らかなように、従来の貼付剤で
は薬剤放出量が比較的短時間のうちに飽和に達し
薬効の持続性に劣つているのに対し、この発明に
係る貼付剤は薬剤放出量の変化がゆるやかで40時
間後においてもなお薬剤の放出が認められる如く
薬効の持続性が非常に改善されている。 As is clear from the above figure, in the conventional patch, the amount of drug released reaches saturation in a relatively short period of time, resulting in poor sustainability of drug efficacy, whereas in the patch according to the present invention, the amount of drug released is The durability of the drug's efficacy has been greatly improved, with gradual changes in drug efficacy and drug release being observed even after 40 hours.
第１図はこの発明法に係る貼付剤の一例を示す
断面図、第２図は第１図の部分の換大図、第３
図は貼付剤の薬剤放出特性を示す特性図である。
１……支持体、２……薬剤含有の粘着剤層。
Figure 1 is a sectional view showing an example of a patch according to the method of this invention, Figure 2 is an enlarged view of the part in Figure 1, and Figure 3
The figure is a characteristic diagram showing the drug release characteristics of the patch. 1... Support, 2... Drug-containing adhesive layer.
Claims (1)
当たり、モノマーを含む粘着性ポリマー組成物を
調製しこれに薬剤を含ませた状態で電離性放射線
を照射して重合架橋させる方法であつて、かつ上
記粘着性ポリマー組成物の調製に際して、（メ
タ）アクリル酸エステルないしビニル系モノマー
と極性モノマーとからなる親油性のモノマー混合
物を用いてこれを重合開始剤により塊状重合させ
る一方、この重合系内に未反応モノマーが残存す
る段階で水または水に水溶性ポリマーその他の添
加剤を含ませた水系混合物を加えて抜熱した後、
要すれば乳化剤を添加して強力撹拌することを特
徴とする貼付剤の製造方法。1. In forming a drug-containing adhesive layer on a support, a method of preparing an adhesive polymer composition containing a monomer and irradiating it with ionizing radiation to polymerize and crosslink the composition with the drug impregnated therein. , and in preparing the adhesive polymer composition, a lipophilic monomer mixture consisting of a (meth)acrylic acid ester or vinyl monomer and a polar monomer is used and bulk polymerized with a polymerization initiator, while this polymerization system At the stage when unreacted monomers remain in the reactor, water or an aqueous mixture of water containing a water-soluble polymer and other additives is added, and the heat is removed.
A method for producing a patch, which comprises adding an emulsifier if necessary and stirring vigorously.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8803980A JPS5714527A (en) | 1980-06-28 | 1980-06-28 | Preparation of plaster |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8803980A JPS5714527A (en) | 1980-06-28 | 1980-06-28 | Preparation of plaster |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5714527A JPS5714527A (en) | 1982-01-25 |
| JPS6248644B2 true JPS6248644B2 (en) | 1987-10-15 |
Family
ID=13931674
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP8803980A Granted JPS5714527A (en) | 1980-06-28 | 1980-06-28 | Preparation of plaster |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5714527A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR102032759B1 (en) | 2018-09-14 | 2019-10-17 | 삼성전기주식회사 | Electronic component |
| KR20190121179A (en) | 2018-09-13 | 2019-10-25 | 삼성전기주식회사 | Electronic component |
| KR20200031086A (en) | 2020-01-22 | 2020-03-23 | 삼성전기주식회사 | Electronic component |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5927821A (en) * | 1982-08-06 | 1984-02-14 | Kanebo Ltd | Poultice agent |
| US20160121018A1 (en) * | 2012-11-21 | 2016-05-05 | Alcare Co., Ltd. | Adhesive composition for skin, adhesive for skin, and adhesive sheet for skin |
-
1980
- 1980-06-28 JP JP8803980A patent/JPS5714527A/en active Granted
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20190121179A (en) | 2018-09-13 | 2019-10-25 | 삼성전기주식회사 | Electronic component |
| KR102032759B1 (en) | 2018-09-14 | 2019-10-17 | 삼성전기주식회사 | Electronic component |
| KR20200031086A (en) | 2020-01-22 | 2020-03-23 | 삼성전기주식회사 | Electronic component |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5714527A (en) | 1982-01-25 |
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