JPS6066758A - Pharmaceutical preparation - Google Patents
Pharmaceutical preparationInfo
- Publication number
- JPS6066758A JPS6066758A JP58175617A JP17561783A JPS6066758A JP S6066758 A JPS6066758 A JP S6066758A JP 58175617 A JP58175617 A JP 58175617A JP 17561783 A JP17561783 A JP 17561783A JP S6066758 A JPS6066758 A JP S6066758A
- Authority
- JP
- Japan
- Prior art keywords
- parts
- pharmaceutical preparation
- acrylic acid
- drug
- meth
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000000825 pharmaceutical preparation Substances 0.000 title claims description 18
- 229940079593 drug Drugs 0.000 claims description 27
- 239000003814 drug Substances 0.000 claims description 27
- 239000000178 monomer Substances 0.000 claims description 15
- 230000009477 glass transition Effects 0.000 claims description 12
- 239000002876 beta blocker Substances 0.000 claims description 11
- 229940097320 beta blocking agent Drugs 0.000 claims description 11
- 239000008280 blood Substances 0.000 claims description 11
- 210000004369 blood Anatomy 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 239000004820 Pressure-sensitive adhesive Substances 0.000 claims description 5
- CIJVBYRUFLGDHY-UHFFFAOYSA-N bucumolol Chemical compound O1C(=O)C=CC2=C1C(OCC(O)CNC(C)(C)C)=CC=C2C CIJVBYRUFLGDHY-UHFFFAOYSA-N 0.000 claims description 5
- 229950002568 bucumolol Drugs 0.000 claims description 5
- 229960002508 pindolol Drugs 0.000 claims description 4
- PHUTUTUABXHXLW-UHFFFAOYSA-N pindolol Chemical compound CC(C)NCC(O)COC1=CC=CC2=NC=C[C]12 PHUTUTUABXHXLW-UHFFFAOYSA-N 0.000 claims description 4
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 4
- 229920002554 vinyl polymer Polymers 0.000 claims description 4
- MPGBPFMOOXKQRX-UHFFFAOYSA-N indenolol Chemical compound CC(C)NCC(O)COC1=CC=CC2=C1C=CC2 MPGBPFMOOXKQRX-UHFFFAOYSA-N 0.000 claims description 3
- 150000003840 hydrochlorides Chemical class 0.000 claims description 2
- 229950008838 indenolol Drugs 0.000 claims description 2
- 229920000642 polymer Polymers 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- 229920001577 copolymer Polymers 0.000 description 11
- 239000007787 solid Substances 0.000 description 11
- -1 (meth)acrylic acid pentyl ester Chemical class 0.000 description 10
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 7
- 239000012298 atmosphere Substances 0.000 description 7
- 229920001971 elastomer Polymers 0.000 description 7
- 239000011261 inert gas Substances 0.000 description 7
- 239000005060 rubber Substances 0.000 description 7
- 238000001035 drying Methods 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 5
- 230000000144 pharmacologic effect Effects 0.000 description 5
- GOXQRTZXKQZDDN-UHFFFAOYSA-N 2-Ethylhexyl acrylate Chemical compound CCCCC(CC)COC(=O)C=C GOXQRTZXKQZDDN-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Substances CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 2
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 2
- 206010002383 Angina Pectoris Diseases 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 239000004952 Polyamide Substances 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- 229920002367 Polyisobutene Polymers 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- POJWUDADGALRAB-UHFFFAOYSA-N allantoin Chemical compound NC(=O)NC1NC(=O)NC1=O POJWUDADGALRAB-UHFFFAOYSA-N 0.000 description 2
- 230000006793 arrhythmia Effects 0.000 description 2
- 206010003119 arrhythmia Diseases 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
- 238000000605 extraction Methods 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000004817 gas chromatography Methods 0.000 description 2
- 239000007935 oral tablet Substances 0.000 description 2
- 230000035699 permeability Effects 0.000 description 2
- 229920002647 polyamide Polymers 0.000 description 2
- 229920001083 polybutene Polymers 0.000 description 2
- 229920000728 polyester Polymers 0.000 description 2
- 229920000573 polyethylene Polymers 0.000 description 2
- 238000006116 polymerization reaction Methods 0.000 description 2
- 229920000193 polymethacrylate Polymers 0.000 description 2
- 229920002635 polyurethane Polymers 0.000 description 2
- 239000004814 polyurethane Substances 0.000 description 2
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 229920003002 synthetic resin Polymers 0.000 description 2
- 239000000057 synthetic resin Substances 0.000 description 2
- OSSNTDFYBPYIEC-UHFFFAOYSA-N 1-ethenylimidazole Chemical compound C=CN1C=CN=C1 OSSNTDFYBPYIEC-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
- OEPOKWHJYJXUGD-UHFFFAOYSA-N 2-(3-phenylmethoxyphenyl)-1,3-thiazole-4-carbaldehyde Chemical compound O=CC1=CSC(C=2C=C(OCC=3C=CC=CC=3)C=CC=2)=N1 OEPOKWHJYJXUGD-UHFFFAOYSA-N 0.000 description 1
- ZDHWTWWXCXEGIC-UHFFFAOYSA-N 2-ethenylpyrimidine Chemical compound C=CC1=NC=CC=N1 ZDHWTWWXCXEGIC-UHFFFAOYSA-N 0.000 description 1
- FWWXYLGCHHIKNY-UHFFFAOYSA-N 2-ethoxyethyl prop-2-enoate Chemical compound CCOCCOC(=O)C=C FWWXYLGCHHIKNY-UHFFFAOYSA-N 0.000 description 1
- ROGIWVXWXZRRMZ-UHFFFAOYSA-N 2-methylbuta-1,3-diene;styrene Chemical compound CC(=C)C=C.C=CC1=CC=CC=C1 ROGIWVXWXZRRMZ-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
- 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
- CFZDMXAOSDDDRT-UHFFFAOYSA-N 4-ethenylmorpholine Chemical compound C=CN1CCOCC1 CFZDMXAOSDDDRT-UHFFFAOYSA-N 0.000 description 1
- BVSNLLUBKCYZDR-UHFFFAOYSA-N 4-methoxy-2-methylidenebutanoic acid Chemical compound COCCC(=C)C(O)=O BVSNLLUBKCYZDR-UHFFFAOYSA-N 0.000 description 1
- RSWGJHLUYNHPMX-UHFFFAOYSA-N Abietic-Saeure Natural products C12CCC(C(C)C)=CC2=CCC2C1(C)CCCC2(C)C(O)=O RSWGJHLUYNHPMX-UHFFFAOYSA-N 0.000 description 1
- POJWUDADGALRAB-PVQJCKRUSA-N Allantoin Natural products NC(=O)N[C@@H]1NC(=O)NC1=O POJWUDADGALRAB-PVQJCKRUSA-N 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- 244000043261 Hevea brasiliensis Species 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
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- KHPCPRHQVVSZAH-HUOMCSJISA-N Rosin Natural products O(C/C=C/c1ccccc1)[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 KHPCPRHQVVSZAH-HUOMCSJISA-N 0.000 description 1
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
- 229940124532 absorption promoter Drugs 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 229960000458 allantoin Drugs 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 239000002519 antifouling agent Substances 0.000 description 1
- 238000005452 bending Methods 0.000 description 1
- 229960000330 bupranolol Drugs 0.000 description 1
- HQIRNZOQPUAHHV-UHFFFAOYSA-N bupranolol Chemical compound CC1=CC=C(Cl)C(OCC(O)CNC(C)(C)C)=C1 HQIRNZOQPUAHHV-UHFFFAOYSA-N 0.000 description 1
- CQEYYJKEWSMYFG-UHFFFAOYSA-N butyl acrylate Chemical compound CCCCOC(=O)C=C CQEYYJKEWSMYFG-UHFFFAOYSA-N 0.000 description 1
- 229920005549 butyl rubber Polymers 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- LDHQCZJRKDOVOX-NSCUHMNNSA-N crotonic acid Chemical compound C\C=C\C(O)=O LDHQCZJRKDOVOX-NSCUHMNNSA-N 0.000 description 1
- 229940031578 diisopropyl adipate Drugs 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 229960004756 ethanol Drugs 0.000 description 1
- UIWXSTHGICQLQT-UHFFFAOYSA-N ethenyl propanoate Chemical compound CCC(=O)OC=C UIWXSTHGICQLQT-UHFFFAOYSA-N 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 239000010408 film Substances 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 230000007803 itching Effects 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- LVHBHZANLOWSRM-UHFFFAOYSA-N methylenebutanedioic acid Natural products OC(=O)CC(=C)C(O)=O LVHBHZANLOWSRM-UHFFFAOYSA-N 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 229920003052 natural elastomer Polymers 0.000 description 1
- 229920001194 natural rubber Polymers 0.000 description 1
- 239000004745 nonwoven fabric Substances 0.000 description 1
- KSCKTBJJRVPGKM-UHFFFAOYSA-N octan-1-olate;titanium(4+) Chemical compound [Ti+4].CCCCCCCC[O-].CCCCCCCC[O-].CCCCCCCC[O-].CCCCCCCC[O-] KSCKTBJJRVPGKM-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000000123 paper Substances 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229920006267 polyester film Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920001195 polyisoprene Polymers 0.000 description 1
- 239000003505 polymerization initiator Substances 0.000 description 1
- 229920000098 polyolefin Polymers 0.000 description 1
- 229920006264 polyurethane film Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 229960003712 propranolol Drugs 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229920002379 silicone rubber Polymers 0.000 description 1
- 239000004945 silicone rubber Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229920006132 styrene block copolymer Polymers 0.000 description 1
- 229920003048 styrene butadiene rubber Polymers 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 229920003051 synthetic elastomer Polymers 0.000 description 1
- 239000005061 synthetic rubber Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 235000010215 titanium dioxide Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- KHPCPRHQVVSZAH-UHFFFAOYSA-N trans-cinnamyl beta-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OCC=CC1=CC=CC=C1 KHPCPRHQVVSZAH-UHFFFAOYSA-N 0.000 description 1
- LDHQCZJRKDOVOX-UHFFFAOYSA-N trans-crotonic acid Natural products CC=CC(O)=O LDHQCZJRKDOVOX-UHFFFAOYSA-N 0.000 description 1
- 229940045136 urea Drugs 0.000 description 1
- 230000002747 voluntary effect Effects 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- 239000002759 woven fabric Substances 0.000 description 1
Abstract
(57)【要約】本公報は電子出願前の出願データであるた
め要約のデータは記録されません。(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.
Description
【発明の詳細な説明】
本発明は高圧血症、狭心症、不整脈症などの疾患の抑制
又は予防に有効なベータ遮断薬を基剤中に含有させた薬
物の経皮投与タイプの医薬製剤に関するものである。DETAILED DESCRIPTION OF THE INVENTION The present invention provides a percutaneous administration type pharmaceutical formulation containing a beta-blocker in a base that is effective for suppressing or preventing diseases such as hypertension, angina, and arrhythmia. It is related to.
従来、ベータ遮断薬の投薬形態として経口錠が主に用い
られているが、該薬物は生体内での半減期が短かく、有
効表血中濃度を維持するためには１日に３回投与する必
要があった。これらの煩雑さを改善する目的で薬理効果
を２４時間持続させる経口錠の開発がオクスブレノロー
ル、プロプラノロール、ピンドロール等のベータ遮断薬
で開発されようとしている。しかしベータ遮断薬は経口
投与した場合に体内での代謝速度が速いので比較的多量
の薬物を投与する必要があシ、そのために副作用の問題
が庄じ、またコスト面で充分に満足の行くものが開発さ
れていないのが現状である。Conventionally, oral tablets have been mainly used as the dosage form for beta-blockers, but these drugs have a short half-life in the body and must be administered three times a day to maintain effective surface blood concentrations. I needed to. In order to alleviate these complications, oral tablets that maintain pharmacological effects for 24 hours are being developed using beta blockers such as oxbrenolol, propranolol, and pindolol. However, when beta blockers are administered orally, they are metabolized quickly in the body, so it is necessary to administer a relatively large amount of the drug, which reduces the problem of side effects, and it is not completely satisfactory in terms of cost. The current situation is that it has not been developed.
本発明者らはかかる欠点を解消するために鋭意研究を重
ねた結果、特定のベータ遮断薬を経皮的に体内に投与す
るととによｐ長時間に亘って持続的に薬理効果が維持用
来ることを見い出し、本発明に至ったものである。The inventors of the present invention have conducted extensive research in order to eliminate such drawbacks, and have found that when a specific beta blocker is administered transdermally into the body, the pharmacological effect can be maintained continuously over a long period of time. This is what led to the present invention.
即ち、本発明は柔軟性を有する担持体上に薬物含有の基
剤層を設けた医薬製剤において、該基剤層が有効血中濃
度３０ Ｈ，ｊ９／Ｉｆ以下のベータ遮断薬とガラス転
移温度−７０〜−１０℃の感圧性接着剤を必須成分とし
て構成されている医薬製剤を提供するものである０
本発明において用いられる感圧性接着剤は、基剤の保型
性の維持や薬物の溶解分散性、その他製剤としての観点
から、ガラス転移温度が−７０〜−１０℃の範囲のもの
がよく、特に好ましくは−５５〜−２５℃の範囲のもの
から選ばれる０本条件を満足しうる感圧性接着剤の主成
分としては合成樹脂及びゴム系物質から選ばれ、例えば
ポリビニルフルキルエーテル、ポリ（メタ）アクリレー
ト、ポリウレタン、ポリエステル、ポリアミド、エチレ
ン−酢酸ビニル共重合体、及びスチレン−イソプレン−
スチレンブロック共重合体ゴム、スチレン−ブタジェン
ブロック共重合体ゴム、°ポリブテンゴム、ポリイソプ
レンゴム、ブチルゴム、シリコーンゴム、天然ゴムなど
が挙げられるｏしかし、上記主成分は単独では必要とす
るガラス転移温度を呈しないものもあるので、それらは
他の成分と組み合わせたシ、一般に使用されている粘着
付与剤などの添加剤を配合することによって必要とする
ガラス転移温度に調整することが出来る０上記主成分中
で皮膚密着性、薬物溶解性、薬物放出性、薬物との相溶
性などを最も満足しうる主成分としてポリ（メタ）アク
リレートが挙げられ、これを構成する主成分単量体とし
てアルキル基の炭素数が４〜１５の（メタ）アクリル酸
アルキルエステル、例えば（メタ）アクリル酸ブチルエ
ステル、（メタ）アクリル酸ペンチルエステル、（メタ
）アクリル酸ヘキシルエステル、（メタ）アクリル酸オ
クチルエステル、（メタ）アクリル酸ノニルエステル、
（メタ）アクリル酸デシルエステル、（メタ）アクリル
酸ドデシルエステル、（メタ）アクリル酸トリデシルエ
ステルの如き単量体が挙げられるが、該単量体のアルキ
ル基は直鎖状又は分岐状であってもよく、添加量は感圧
性接着剤中５０重門％以上が好ましい。該単量体は薬物
含有の基剤層に支局接着性を付与する成分であり、５０
″ｇ、量％以下では医薬製剤を皮膚に貼付使用した際に
端末ハガレや医薬製剤の脱落現象が生じる場合がある。That is, the present invention provides a pharmaceutical preparation in which a drug-containing base layer is provided on a flexible carrier, in which the base layer contains a beta blocker with an effective blood concentration of 30 H, j9/If or less and a glass transition temperature. The present invention provides a pharmaceutical preparation that includes a pressure-sensitive adhesive with a temperature of -70 to -10°C as an essential component. From the viewpoint of dissolution and dispersibility and other formulations, it is preferable to have a glass transition temperature in the range of -70 to -10°C, particularly preferably in the range of -55 to -25°C, which satisfies the following conditions. The main component of the sticky pressure-sensitive adhesive is selected from synthetic resins and rubber-based substances, such as polyvinylfurkyl ether, poly(meth)acrylate, polyurethane, polyester, polyamide, ethylene-vinyl acetate copolymer, and styrene-isoprene.
Examples include styrene block copolymer rubber, styrene-butadiene block copolymer rubber, polybutene rubber, polyisoprene rubber, butyl rubber, silicone rubber, natural rubber, etc. However, the above main components alone do not require a glass transition. Some materials do not exhibit a temperature change, so they can be adjusted to the required glass transition temperature by combining them with other ingredients or adding commonly used additives such as tackifiers. Among the main components, poly(meth)acrylate is the main component that best satisfies skin adhesion, drug solubility, drug release, and compatibility with drugs, and the main component monomers that make it are alkyl (meth)acrylic acid alkyl esters in which the group has 4 to 15 carbon atoms, such as (meth)acrylic acid butyl ester, (meth)acrylic acid pentyl ester, (meth)acrylic acid hexyl ester, (meth)acrylic acid octyl ester, (meth)acrylic acid nonyl ester,
Monomers such as (meth)acrylic acid decyl ester, (meth)acrylic acid dodecyl ester, and (meth)acrylic acid tridecyl ester are mentioned, but the alkyl group of the monomer may be linear or branched. The amount added is preferably 50% or more in the pressure-sensitive adhesive. The monomer is a component that imparts local adhesion to the drug-containing base layer, and has a molecular weight of 50
If the amount is less than 100% by weight, peeling of the terminal or detachment of the pharmaceutical preparation may occur when the pharmaceutical preparation is applied to the skin.
また上記主成分単量体と共重合可能なビニル系単量体及
び／又は極性単量体は基剤層に薬物溶解性及び凝集性を
付与する成分であると共に、微妙な選択調整によシ基剤
層からの薬物の放出速度又は放出量を制御することが出
来る０共重合可能なビニル系単量体として、例えば酢酸
ビニル、プロピオン酸ビニル、ビニルピロリドン、ビニ
ルピリジン、ビニルピリミジン、ビニルイミダゾール、
ビニルモルホリン、スチｌ／ンの如き単量体が挙げられ
る。また極性単量体とし丁、例えば（メタ）アクリル酸
、イタコン酸、マレイン酸、無水マレイン酸、クロトン
酸、（メタ）アクリル酸ヒドロキシエチルエステル、（
メタ）アクリル酸ヒドロキシプロピルエステル、（メタ
）アクリルアミド、ジメチル（メタ）アクリルアミド、
（メタ）アクリル酸ジメチルアミノエチルエステル、（
メタ）アクリル酸ｔ−ブチルアミノエチルエステル、（
メタ）アクリル酸メトキシエチルエステルの如き単量体
が挙げられ、これらの共重合可能なビニル系単量体及び
極性単量体の添加量はそれぞれ４０重量％以下、及び２
０重量％以下でアシ、好ましくは１０〜３０重量％、及
び０．５〜１５重量％の範囲で使用に供される。添加蓋
が上記範囲外では薬物溶解性、凝集性、皮膚接着性、放
出速度のバランスが崩れるために望ましい接着特性や薬
理効果が得られない場合が生じる。In addition, the vinyl monomer and/or polar monomer that can be copolymerized with the above main component monomer are components that impart drug solubility and cohesiveness to the base layer, and can be easily adjusted by delicate selection adjustment. Copolymerizable vinyl monomers that can control the rate or amount of drug release from the base layer include, for example, vinyl acetate, vinyl propionate, vinylpyrrolidone, vinylpyridine, vinylpyrimidine, vinylimidazole,
Examples include monomers such as vinylmorpholine and styrene. In addition, polar monomers such as (meth)acrylic acid, itaconic acid, maleic acid, maleic anhydride, crotonic acid, (meth)acrylic acid hydroxyethyl ester, (
meth)acrylic acid hydroxypropyl ester, (meth)acrylamide, dimethyl(meth)acrylamide,
(meth)acrylic acid dimethylaminoethyl ester, (
meth)acrylic acid t-butylaminoethyl ester, (
Examples include monomers such as methoxyethyl acrylic acid ester, and the amounts of these copolymerizable vinyl monomers and polar monomers are 40% by weight or less, and 2% by weight or less, respectively.
It can be used in a range of 0% by weight or less, preferably 10 to 30% by weight, and 0.5 to 15% by weight. If the additive amount is outside the above range, the balance between drug solubility, cohesiveness, skin adhesion, and release rate will be disrupted, so that desired adhesive properties and pharmacological effects may not be obtained.
本発明において使用される担持体は医薬製剤を皮膚面に
適用した際に著しい異和感が生じない程度の柔軟性を有
するものであれば特に材質に制限はない。このような担
持体としては、例えばポリオレフィン、ポリエステル、
ポリウレタン、ポリビニルアルコール、塩化ビニリデン
、ポリアミドなどの合成樹脂製フィルム、ゴム系フィル
ム、不織布、織布、紙類、金属箔、又はこれらの積層フ
ィルムなどが挙げられる。該担持体は場合によって適用
皮膚面に痒みや接触による炎症を生じることがらシ、実
質的に透湿性、通気性又は柔軟性を有しないような担持
体には孔部や切れ目を施こし適度の通気性や柔軟性を付
与することも出来る。The material of the carrier used in the present invention is not particularly limited as long as it has flexibility to the extent that no significant discomfort occurs when the pharmaceutical preparation is applied to the skin surface. Examples of such carriers include polyolefins, polyesters,
Examples include films made of synthetic resins such as polyurethane, polyvinyl alcohol, vinylidene chloride, and polyamide, rubber films, nonwoven fabrics, woven fabrics, papers, metal foils, and laminated films thereof. In some cases, the carrier may cause itching or irritation on the skin surface to which it is applied, so if the carrier does not have substantially moisture permeability, air permeability, or flexibility, holes or slits may be provided to provide adequate protection. It can also provide breathability and flexibility.
更に、屈曲部への適用を考慮すると、少なくとも１０％
、好ましくは５０％以上で実用的には１００〜８００％
の伸縮性を有する材質のもの、或いは伸縮加工を施こし
たものが望ましい。Furthermore, considering application to bending parts, at least 10%
, preferably 50% or more, practically 100-800%
It is desirable that the material be made of a material that has elasticity, or that has been subjected to a stretching process.
本発明において用いられるベータ遮断薬は経皮吸収によ
って体内投与するために有効血中濃度が３０ ｎ ｊｉ
／Ｋｌ以下のものが適しておｐｌ例えばブフラノロール
、インデノロール、フクモロール、およびこれらの塩酸
塩、及びピンドロールが最適である。有効血中濃度が３
０部ｇ／Ｌｌ！以上の高濃度維持が必要なベータ遮断薬
は経皮吸収量の限界以上の血中濃度を必要とするため、
満足ゆく有効血中濃度に達せず、高血圧症、狭心症、不
整脈症などの疾病治癒に効果を発揮し難い。これらの薬
物の添加量は基剤胴中に０．５〜２０重量％、好ましく
は２〜１５重量％の範囲が望ましい。The beta blocker used in the present invention has an effective blood concentration of 30 n ji in order to be administered into the body by transdermal absorption.
/Kl or less, such as bufranolol, indenolol, fucumolol, their hydrochlorides, and pindolol are most suitable. Effective blood concentration is 3
0 part g/Ll! Beta-blockers that require maintenance of high concentrations require blood concentrations that exceed the limit of transdermal absorption.
It does not reach a satisfactory effective blood concentration, making it difficult to exert effects on curing diseases such as hypertension, angina pectoris, and arrhythmia. The amount of these drugs added to the base body is preferably 0.5 to 20% by weight, preferably 2 to 15% by weight.
さらに本発明の医薬部材の保型性を維持したり、経皮吸
収性を更に向上させて充分な薬理効果を発揮させる目的
で、薬物含有の基剤層中に充填剤又は経皮吸収促進助剤
などを添加することが出来る。Furthermore, in order to maintain the shape retention of the medicinal component of the present invention and to further improve transdermal absorbability to exhibit a sufficient pharmacological effect, fillers or transdermal absorption promoters are added to the drug-containing base layer. Agents etc. can be added.
充填剤としては、例えば微粉末シリカ、チタン白、炭酸
カルシウム、カオリンなどの無機物が好適であシ、経皮
吸収促進助剤としては、例えばプロピレングリコール、
ジエチレングリコール、ポリエチレングリコールの如き
グリコール類、エチルアルコール、サリチル酸、尿素、
アラントイン、ジメチルスルホキシド、ジメチルホルム
アミド、ジメチルアセトアミド、ジイソプロピルアジペ
ート、ジエチルセバケート、エチルラウレート、Ｈｌ−
面活性剤などの如き物質が挙げられ、前者は基剤層に対
して２０重量％以下の量で、また後者は基剤に対して３
０重量％以下の量で添加することが出来る。また基剤層
中に一般的に粘着性付与剤、軟化剤の如き配合剤や、カ
ニＥＪｈめ剤やカブレ防止剤の如き薬物を少量添加する
ことも出来る。As the filler, for example, inorganic substances such as finely powdered silica, titanium white, calcium carbonate, and kaolin are suitable.As the transdermal absorption promoting agent, for example, propylene glycol,
Glycols such as diethylene glycol and polyethylene glycol, ethyl alcohol, salicylic acid, urea,
Allantoin, dimethyl sulfoxide, dimethylformamide, dimethylacetamide, diisopropyl adipate, diethyl sebacate, ethyl laurate, Hl-
Substances such as surfactants may be mentioned, the former in an amount of 20% by weight or less based on the base layer, and the latter in an amount of 3% by weight based on the base layer.
It can be added in an amount of 0% by weight or less. In addition, small amounts of compounding agents such as tackifiers and softeners, and drugs such as crab emollients and antifouling agents can also be generally added to the base layer.
前記に示した薬物含有の基剤層は柔軟性を有する担持体
上に５〜３００μｍの厚みで全面、又は部分的に設ける
ことが出来る。特に基剤層を部分的に設ける際に、筋状
、格子状、波形状などのパターン塗工を施こしたシ、更
に二種類以上のガラス転移温度が異々つだ基剤層を担持
体上に交互に設けたり、海島状に設けることによっても
含有する薬物の放出量及び放出速度の制御が可能である
。The drug-containing base layer shown above can be provided entirely or partially on a flexible carrier with a thickness of 5 to 300 μm. In particular, when the base layer is partially provided, the base layer is coated with a pattern such as streaks, grids, or waves, and the base layer has two or more different glass transition temperatures. It is also possible to control the release amount and release rate of the drug contained therein by providing them alternately or in a sea-island pattern.
また薬物の放ＩＪＪ性を制御する目的で、担持体上に二
種類以上の基剤層を積層することも出来る。積層形態を
利用した場合、担持体に接する側の基剤層から順に薬物
含有量を減少させると長期間接続タイプになシ、又逆の
構成を施すと初期大量投与タイプとな勺、これらは治療
の目的に応じて選択することが出来る。Furthermore, for the purpose of controlling the IJJ properties of drug release, two or more types of base layers can be laminated on the carrier. When using a laminated structure, if the drug content is reduced sequentially from the base layer in contact with the carrier, a long-term connection type will not be obtained, and if the reverse configuration is applied, an initial large-dose administration type will be obtained. It can be selected depending on the purpose of treatment.
以上のように本発明の医薬製剤を皮膚面に適用すると、
該医薬製剤の完全な密着性や優れた薬物溶解能によ企適
度な放出性によって、ベータ遮断薬が確実に皮膚面を経
て体内吸収されるので、疾患治療に充分な薬理効果を発
揮することが出来る。When the pharmaceutical formulation of the present invention is applied to the skin surface as described above,
Due to the perfect adhesion and excellent drug solubility of the pharmaceutical preparation, the beta blocker is reliably absorbed into the body through the skin, and exhibits sufficient pharmacological effects for disease treatment. I can do it.
以下に本発明の実施例を示し、さらに具体的に説明する
が、本発明はこれらに限定されるものではなく、技術的
思想を逸脱しない範囲で種々の応用が可能である。なお
実施例中で部とあるのは重量部を示す。Examples of the present invention will be shown below and will be described in more detail, but the present invention is not limited to these and can be applied in various ways without departing from the technical idea. Note that parts in the examples indicate parts by weight.
実施例１
トルエン／酢酸エチル（２／１ ）混合溶剤２５０部に
ピンドロールを５部溶解し、更にポリイソブチレンゴム
（粘度平均分子量１２０万）２０部及びポリイソブチレ
ンゴム（粘度平均分子量３．５万）３０部を添加して充
分に溶解させた後、ポリブテン２０部及びウッドロジン
３０部を添加し、充分に撹拌混合して薬物含有の基剤溶
液を調製した。Example 1 5 parts of pindolol was dissolved in 250 parts of toluene/ethyl acetate (2/1) mixed solvent, and further 20 parts of polyisobutylene rubber (viscosity average molecular weight 1,200,000) and polyisobutylene rubber (viscosity average molecular weight 35,000) were dissolved. After adding 30 parts and sufficiently dissolving it, 20 parts of polybutene and 30 parts of wood rosin were added and thoroughly stirred and mixed to prepare a drug-containing base solution.
（薬物不合での配合物のガラス転移温度−４０℃）調製
された基剤溶液を剥離ライナー上に乾燥後の厚みが１０
０μ集となるように塗布、乾燥して造膜化し、次に軟質
ポリ塩化ビニルフィルム」二に転着して医薬製剤を得た
。(Glass transition temperature of the formulation at drug mismatch -40°C) The prepared base solution was placed on a release liner to a thickness of 10°C after drying.
A film was formed by coating and drying to obtain a 0μ film, and then transferred to a soft polyvinyl chloride film to obtain a pharmaceutical preparation.
実施例２
アクリル酸イソオクチルエステル及びアクリル酸ｎ−ブ
チルエステルを各々５０部、酢酸エチル２５部を不活性
ガス雰囲気下でフラスコ内に仕込み５重合開始剤として
の７ゾイソブチロニトリル０．３部を添加して重合を開
始させ、酢酸エチルを滴下、撹拌しつつ反応温度を６０
〜６４℃に制御して８時間重合反応を行ない、固形分濃
度４０重量％、３０℃での４０％溶液粘度４１０ポイズ
の共重合体（ガラス転移温度−５１℃）の溶液を得た。Example 2 50 parts each of acrylic acid isooctyl ester and acrylic acid n-butyl ester and 25 parts of ethyl acetate were charged into a flask under an inert gas atmosphere, and 0.3 part of 7zoisobutyronitrile was added as a polymerization initiator. was added to start polymerization, ethyl acetate was added dropwise, and the reaction temperature was raised to 60°C while stirring.
The polymerization reaction was carried out at a temperature of -64°C for 8 hours to obtain a solution of a copolymer (glass transition temperature -51°C) having a solid content concentration of 40% by weight and a 40% solution viscosity of 410 poise at 30°C.
得られた共重合体溶液の固形分１００部に対してブプラ
ノロール８部を象加混合し、剥離ライナー上に乾燥後の
厚みが５０μ雪となるように塗布、乾燥して皮膜化し、
次にポリエチレンフィルム上に転着して医薬製剤を得た
。8 parts of bupranolol was added and mixed with 100 parts of the solid content of the obtained copolymer solution, and applied on the release liner to a thickness of 50 μm after drying, dried to form a film,
Next, the mixture was transferred onto a polyethylene film to obtain a pharmaceutical preparation.
実施例３
アクリル酸２−エチルヘキシルエステル９３部、アクリ
ル酸７部、酢酸エチル２５部を不活性ガス雰囲気下でフ
ラスコ内に仕込み、以下実施例２と同様の操作によって
固形分濃度４０重量％、３０℃での４０％溶液粘度３０
５ポイズの共重合体（ガラス転移温度−５５℃）の溶液
を得た。Example 3 93 parts of acrylic acid 2-ethylhexyl ester, 7 parts of acrylic acid, and 25 parts of ethyl acetate were charged into a flask under an inert gas atmosphere, and the solid content concentration was 40% by weight and 30% by the same operation as in Example 2. 40% solution viscosity at °C 30
A solution of a 5 poise copolymer (glass transition temperature -55°C) was obtained.
得られた共重合体溶液の固形分１００部に対して塩酸イ
ンデノロール５部を添加混合し、以下実施例２と同様の
操作によって医薬製剤を得た。5 parts of indenolol hydrochloride were added to and mixed with 100 parts of the solid content of the obtained copolymer solution, and the same procedure as in Example 2 was performed to obtain a pharmaceutical preparation.
実施例４
アクリル酸２−エチルヘキシルエステル７４部、アクリ
ル酸６ｓ、酢酸ビニル２０部、酢酸ビニル２５部を不活
性ガス雰囲気下でフラスコ中に仕込み、以下実施例２と
同様の操作によって固形分濃度３７重量％、３０℃での
４０％溶液粘度５３０ポイズの共重合体（ガラス転移温
度−４５℃）の溶液を得た。Example 4 74 parts of acrylic acid 2-ethylhexyl ester, 6s of acrylic acid, 20 parts of vinyl acetate, and 25 parts of vinyl acetate were charged into a flask under an inert gas atmosphere, and the solid content concentration was adjusted to 37 by the same operation as in Example 2. A solution of a copolymer (glass transition temperature -45°C) having a solution viscosity of 530 poise at 40% by weight at 30°C was obtained.
得られた共重合体溶液の固形分１００部に対してブクモ
ロール５部を添加混合し、以下実施例２と同様の操作に
よって医薬製剤を得た。5 parts of bucumolol was added and mixed to 100 parts of the solid content of the obtained copolymer solution, and the same procedure as in Example 2 was performed to obtain a pharmaceutical preparation.
実施例５
アクリル酸２−エチルヘキシルエステル５５部、アクリ
ル酸２−エトキシエチルエステル１５部、酢酸ビニル３
０部、酢酸エチル２５部を不活性ガス雰囲気下でフラス
コ中に仕込み、以下実施例２と同様の操作によって固形
分濃度３６重量％、３０℃での４０％溶液粘度６９０ポ
イズの共重合体（ガラス転移温度−４７℃）の溶液を得
た。Example 5 55 parts of 2-ethylhexyl acrylate, 15 parts of 2-ethoxyethyl acrylate, 3 parts of vinyl acetate
0 parts and 25 parts of ethyl acetate were charged into a flask under an inert gas atmosphere, and the same procedure as in Example 2 was carried out to prepare a copolymer (solid content concentration: 36% by weight, 40% solution viscosity at 30°C: 690 poise). A solution with a glass transition temperature of -47°C was obtained.
得られた共重合体だ液の固形分１００部に対してブクモ
ロール５部を添加混合し、ポリウレタンフィルム上に乾
燥後の厚みが５０μｍとなるように塗布、乾燥して皮膜
化し医薬製剤を得た。5 parts of bucumolol was added and mixed to 100 parts of the solid content of the obtained copolymer saliva, and the mixture was coated on a polyurethane film to a thickness of 50 μm after drying, and dried to form a film to obtain a pharmaceutical preparation. .
実施例６
実施例３及び４にて得られた共重合体溶液の固形分１０
０部に対して各々ブクモロールを５部ずつ添加混合した
溶液を、１２μ脩の厚みポリエステルフィルムの片面に
乾燥後の厚みが５０μｍになるように各々４Ｏｔｔｒｍ
幅で交互に塗布、乾燥して皮膜化し筋状に二種の基剤を
交互に設けた医薬製剤を得た０
各実施例にて得られた医薬製剤を皮膚面に適用した際の
皮膚密着性及び薬物移行率を第１表に示し、貼付後の各
時間における血中濃度の推移を第２表に示した。なお、
各試験方法は以下の通シでめる０
〈皮膚密着性〉
各実施例における医薬製剤の試験片（５Ｘ５ｃ４）を上
腕部内側に貼付し、貼付時と１２時間貼付後の皮膚面へ
の密着性を以下の基準にて判走した。Example 6 Solid content of copolymer solutions obtained in Examples 3 and 4: 10
Add and mix a solution of 5 parts each of bucumolol to 0 parts, and apply 4 ottrms of each to one side of a 12 μm thick polyester film so that the thickness after drying is 50 μm.
A pharmaceutical formulation was obtained in which two types of bases were alternately applied in widths, dried to form a film, and two types of bases were alternately provided in a striped manner.0 Adhesion to the skin when the pharmaceutical formulations obtained in each example were applied to the skin surface. Table 1 shows the properties and drug transfer rate, and Table 2 shows the changes in blood concentration at various times after application. In addition,
Each test method can be found in the following guidelines.0 <Skin adhesion> A test piece (5 x 5c4) of the pharmaceutical formulation in each example was pasted on the inside of the upper arm, and the adhesion to the skin surface was measured at the time of application and after 12 hours of application. The gender was determined based on the following criteria.
良：全面にわたって密着性良好
可二周辺部に僅か浮きがあるが良好
不可二周辺部にかなシ浮きがあるか、脱落゛〈薬物移行
率〉
各実施例における医薬製剤の試験片（５Ｘ５ｃＪ）を上
腕部内側に２４時間貼付後、該試験片中の残存量を４０
℃の温度下、振盪機中にて酢酸エチルで溶解抽出し、５
０ｄにメスアップしてガスクロマトグラフィーを用いて
定量した。薬物移行率は以下の式にて算出した。Good: Adhesion is good over the entire surface.2 There is slight lifting at the periphery, but not good.2.There is slight lifting at the periphery or it falls off.゛<Drug transfer rate> After applying it to the inside of the upper arm for 24 hours, the remaining amount in the test piece was reduced to 40
Dissolve and extract with ethyl acetate in a shaker at a temperature of 5°C.
The volume was increased to 0d and quantified using gas chromatography. The drug transfer rate was calculated using the following formula.
〈血中濃度〉
各実施例における医薬製剤の試験片（１０×１０ｅ４）
を３０〜４５才の男性３名の上腕部内側に貼付後、所定
時間毎に５ｄずつ採血を行ない血漿を分離し、３−のｎ
−ヘキサンにて薬物抽出後、遠心分離し不活性ガス雰囲
気下で０．５ｍ／に濃縮する。更に１−のアセトニトリ
ルにて抽出後、アセトニトリル層を不活性ガス雰囲気下
で蒸発乾固し、１００μｌのベンベンにて薬物を溶解し
てガスクロマトグラフィーを用いて定量した。<Blood concentration> Test piece of pharmaceutical preparation in each example (10 x 10e4)
After applying it to the inside of the upper arm of three men aged 30 to 45, blood was collected for 5 days at predetermined intervals and plasma was separated.
- After drug extraction with hexane, it is centrifuged and concentrated to 0.5 m/cm under an inert gas atmosphere. After further extraction with 1-acetonitrile, the acetonitrile layer was evaporated to dryness under an inert gas atmosphere, and the drug was dissolved in 100 μl of benben and quantified using gas chromatography.
第 １ 表
上記実施例からも明白な」：うに、本発明の医薬製剤を
皮膚面に貼付した際、皮膚密着性に優れ、且つ薬物の放
出性が良好でアシ、貼付適用の数時間後に有効血中濃度
に達するという事実が顕著である。Table 1: It is clear from the above examples that when the pharmaceutical preparation of the present invention is applied to the skin, it has excellent skin adhesion and good drug release, and is effective several hours after application. The fact that blood concentrations are reached is remarkable.
特許出願人
日東電気工業株式会社
代表者 土 方 三 部
（自発）手続補正書
昭和５９年 −２６日
特許庁長官 若杉和夫殿
１、事件の表示
昭和５８年特許願第 １７５６１７号
２、発明の名称
医薬製剤
３、補正をする者
事件との関係 特許出願人
４、 の日付
５、補正の対象
明細冑の「発明の詳細な説明」の楯
１）明細書第７頁第１０行目の「ブクモロール、」のあ
とに「ニプラジロール、」を挿入する。Patent Applicant Nitto Electric Industry Co., Ltd. Representative Hijikata Third Division (Voluntary) Procedural Amendment 1981-26 Director General of the Patent Office Kazuo Wakasugi 1 Indication of the Case 1989 Patent Application No. 175617 2 Title of the Invention Pharmaceutical formulation 3. Relationship with the case of the person making the amendment Patent applicant 4. Date of Insert "Nipradirol," after ",".
２）同第１３頁第１１行目と第１２仔細の間に以下の語
句を挿入する。2) Insert the following phrase between the 11th line and the 12th detail on page 13.
「実施例７
アクリル酸２−エチルヘキシルエステル６０部、ｙクリ
ｔｖ酸２−メトキシ上ナルエステル３０部、酢酸ビニル
１０部、酢酸エチル２０部を不活性ガス雰囲気下でフラ
スコ内に仕込み、以下実施例２と同様の操作によって固
形分濃度３５重量％、３０℃での４０％溶液粘度５３０
ホイズの共重合体（ガラス転移温度−３６℃）の溶液を
得た。Example 7 60 parts of acrylic acid 2-ethylhexyl ester, 30 parts of ycritvic acid 2-methoxynal ester, 10 parts of vinyl acetate, and 20 parts of ethyl acetate were charged into a flask under an inert gas atmosphere, and the following examples were prepared. By the same operation as in 2, the solid content concentration was 35% by weight, and the viscosity of the 40% solution at 30°C was 530.
A solution of a copolymer of Hoiz (glass transition temperature -36°C) was obtained.
得られた共重合体溶液の固形分１００部に対してニプラ
ジロール５部を添加混合し、ポリエチレンフィルム上に
乾燥後の厚みが５０μ慨となるように塗布、乾燥して皮
膜化し医薬製剤を得た。」３）同第１５頁の第１表を以
下の通シに補正する。5 parts of nipradirol was added and mixed to 100 parts of the solid content of the obtained copolymer solution, and the mixture was coated on a polyethylene film to a thickness of 50 μm after drying, and dried to form a film to obtain a pharmaceutical preparation. . 3) Table 1 on page 15 of the same is amended as follows.
第 １ 表 ）４）同第１５頁の第２表を以下の通シに補正する。Table 1 )4) Table 2 on page 15 of the same is amended as follows.
毘２表 以上Bi2 table that's all
Claims (3)
けた医薬製剤において、該基剤層が有効血中濃度３０
ｎ、ｆ／Ｍ以下のベータ遮断薬とガラス転移温度−７０
〜−１０℃の感圧性接着剤を必須成分として構成されて
いる医薬製剤０(1) In a pharmaceutical preparation in which a drug-containing base layer is provided on a flexible carrier, the base layer has an effective blood concentration of 30
Beta blockers below n, f/M and glass transition temperature -70
Pharmaceutical preparations consisting of ~-10°C pressure-sensitive adhesive as an essential component 0
テルと、他の共重合可能なビニル系単量体及び／又は極
性単量体との重合体でおる特許請求の範囲第１項記載の
医薬製剤０(2) The pressure-sensitive adhesive is a polymer of (meth)acrylic acid alkyl ester and other copolymerizable vinyl monomers and/or polar monomers according to claim 1. Pharmaceutical preparation 0
、ブクモロール、又はこれらの塩酸塩、及びピンドロー
ルの群から選ばれた一種である特許請求の範囲第１項記
載の医薬製剤０(3) Pharmaceutical formulation 0 according to claim 1, wherein the beta blocker is one selected from the group of bucumolol, indenolol, bucumolol, or their hydrochlorides, and pindolol.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP58175617A JPS6066758A (en) | 1983-09-21 | 1983-09-21 | Pharmaceutical preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP58175617A JPS6066758A (en) | 1983-09-21 | 1983-09-21 | Pharmaceutical preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6066758A true JPS6066758A (en) | 1985-04-16 |
| JPH046163B2 JPH046163B2 (en) | 1992-02-05 |
Family
ID=15999212
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP58175617A Granted JPS6066758A (en) | 1983-09-21 | 1983-09-21 | Pharmaceutical preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6066758A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS62167724A (en) * | 1986-01-13 | 1987-07-24 | アルザ・コ−ポレ−シヨン | Percutaneous drug administration equipment |
| JPH0315477A (en) * | 1988-12-22 | 1991-01-23 | Lts Lohmann Therapie Syst Gmbh & Co Kg | Health care system with physostiqmine as active ingredient through skin and preparation thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS57116011A (en) * | 1981-01-08 | 1982-07-19 | Nitto Electric Ind Co Ltd | Pharmaceutical preparation |
| JPS5838213A (en) * | 1981-08-31 | 1983-03-05 | Nitto Electric Ind Co Ltd | Medical preparation |
-
1983
- 1983-09-21 JP JP58175617A patent/JPS6066758A/en active Granted
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS57116011A (en) * | 1981-01-08 | 1982-07-19 | Nitto Electric Ind Co Ltd | Pharmaceutical preparation |
| JPS5838213A (en) * | 1981-08-31 | 1983-03-05 | Nitto Electric Ind Co Ltd | Medical preparation |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS62167724A (en) * | 1986-01-13 | 1987-07-24 | アルザ・コ−ポレ−シヨン | Percutaneous drug administration equipment |
| JPH0811726B2 (en) * | 1986-01-13 | 1996-02-07 | アルザ・コ−ポレ−シヨン | Transdermal drug administration device |
| JPH0315477A (en) * | 1988-12-22 | 1991-01-23 | Lts Lohmann Therapie Syst Gmbh & Co Kg | Health care system with physostiqmine as active ingredient through skin and preparation thereof |
| JPH0784379B2 (en) * | 1988-12-22 | 1995-09-13 | エル テー エス ローマン テラピー・システーメ ゲー．エム．ベー．ハー ウント コンパニー カー．ゲー | Transdermal drug having physostigmine as an active ingredient and method for producing the same |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH046163B2 (en) | 1992-02-05 |
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