JP5850371B2 - 貼付剤 - Google Patents
貼付剤 Download PDFInfo
- Publication number
- JP5850371B2 JP5850371B2 JP2012536585A JP2012536585A JP5850371B2 JP 5850371 B2 JP5850371 B2 JP 5850371B2 JP 2012536585 A JP2012536585 A JP 2012536585A JP 2012536585 A JP2012536585 A JP 2012536585A JP 5850371 B2 JP5850371 B2 JP 5850371B2
- Authority
- JP
- Japan
- Prior art keywords
- saturated aliphatic
- donepezil
- adhesive layer
- sensitive adhesive
- pressure
- 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.)
- Active
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- ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 claims description 264
- 239000010410 layer Substances 0.000 claims description 156
- 229960003530 donepezil Drugs 0.000 claims description 131
- 239000004820 Pressure-sensitive adhesive Substances 0.000 claims description 123
- 150000003839 salts Chemical class 0.000 claims description 90
- -1 saturated aliphatic alcohols Chemical class 0.000 claims description 89
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical class C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 claims description 77
- 239000012790 adhesive layer Substances 0.000 claims description 55
- 229920006395 saturated elastomer Polymers 0.000 claims description 44
- 150000007933 aliphatic carboxylic acids Chemical class 0.000 claims description 42
- 150000001875 compounds Chemical class 0.000 claims description 20
- 239000000178 monomer Substances 0.000 claims description 19
- 150000005690 diesters Chemical class 0.000 claims description 17
- 150000002148 esters Chemical class 0.000 claims description 17
- 150000005691 triesters Chemical class 0.000 claims description 17
- 229920002678 cellulose Polymers 0.000 claims description 15
- 235000010980 cellulose Nutrition 0.000 claims description 15
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 claims description 12
- 125000001931 aliphatic group Chemical group 0.000 claims description 12
- 229920001577 copolymer Polymers 0.000 claims description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- 239000003522 acrylic cement Substances 0.000 claims description 9
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 238000004090 dissolution Methods 0.000 claims description 4
- 125000003277 amino group Chemical group 0.000 claims description 2
- 150000001735 carboxylic acids Chemical class 0.000 claims 1
- 229920000642 polymer Polymers 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
- 235000019441 ethanol Nutrition 0.000 description 37
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 33
- 238000012360 testing method Methods 0.000 description 30
- 239000013078 crystal Substances 0.000 description 26
- 238000003860 storage Methods 0.000 description 22
- 239000000243 solution Substances 0.000 description 21
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 20
- 239000002904 solvent Substances 0.000 description 19
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 18
- 238000004519 manufacturing process Methods 0.000 description 18
- 150000001335 aliphatic alkanes Chemical class 0.000 description 17
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 17
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 16
- 229920000139 polyethylene terephthalate Polymers 0.000 description 16
- 239000005020 polyethylene terephthalate Substances 0.000 description 16
- 230000001070 adhesive effect Effects 0.000 description 14
- 239000000853 adhesive Substances 0.000 description 13
- 238000001556 precipitation Methods 0.000 description 13
- 238000011282 treatment Methods 0.000 description 13
- 239000003814 drug Substances 0.000 description 11
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 10
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 9
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 9
- 229920001296 polysiloxane Polymers 0.000 description 9
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- 230000000052 comparative effect Effects 0.000 description 8
- 230000007423 decrease Effects 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- HLZKNKRTKFSKGZ-UHFFFAOYSA-N tetradecan-1-ol Chemical compound CCCCCCCCCCCCCCO HLZKNKRTKFSKGZ-UHFFFAOYSA-N 0.000 description 8
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 8
- 239000001856 Ethyl cellulose Substances 0.000 description 7
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 7
- 125000000217 alkyl group Chemical group 0.000 description 7
- 235000019325 ethyl cellulose Nutrition 0.000 description 7
- 229920001249 ethyl cellulose Polymers 0.000 description 7
- 239000003505 polymerization initiator Substances 0.000 description 7
- 239000011347 resin Substances 0.000 description 7
- 229920005989 resin Polymers 0.000 description 7
- 231100000245 skin permeability Toxicity 0.000 description 7
- KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- MWKFXSUHUHTGQN-UHFFFAOYSA-N decan-1-ol Chemical compound CCCCCCCCCCO MWKFXSUHUHTGQN-UHFFFAOYSA-N 0.000 description 6
- 238000000151 deposition Methods 0.000 description 6
- LQZZUXJYWNFBMV-UHFFFAOYSA-N dodecan-1-ol Chemical compound CCCCCCCCCCCCO LQZZUXJYWNFBMV-UHFFFAOYSA-N 0.000 description 6
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 6
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 6
- 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 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
- 239000000654 additive Substances 0.000 description 5
- 239000003431 cross linking reagent Substances 0.000 description 5
- 230000008021 deposition Effects 0.000 description 5
- 229940031578 diisopropyl adipate Drugs 0.000 description 5
- 239000000945 filler Substances 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000004745 nonwoven fabric Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 239000003381 stabilizer Substances 0.000 description 5
- WNWHHMBRJJOGFJ-UHFFFAOYSA-N 16-methylheptadecan-1-ol Chemical compound CC(C)CCCCCCCCCCCCCCCO WNWHHMBRJJOGFJ-UHFFFAOYSA-N 0.000 description 4
- XDOFQFKRPWOURC-UHFFFAOYSA-N 16-methylheptadecanoic acid Chemical compound CC(C)CCCCCCCCCCCCCCC(O)=O XDOFQFKRPWOURC-UHFFFAOYSA-N 0.000 description 4
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 4
- 239000004342 Benzoyl peroxide Substances 0.000 description 4
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 4
- 239000004698 Polyethylene Substances 0.000 description 4
- 230000000996 additive effect Effects 0.000 description 4
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 4
- 235000019400 benzoyl peroxide Nutrition 0.000 description 4
- 230000005540 biological transmission Effects 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 239000012295 chemical reaction liquid Substances 0.000 description 4
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 4
- 239000001087 glyceryl triacetate Substances 0.000 description 4
- 235000013773 glyceryl triacetate Nutrition 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- NMRPBPVERJPACX-UHFFFAOYSA-N octan-3-ol Chemical compound CCCCCC(O)CC NMRPBPVERJPACX-UHFFFAOYSA-N 0.000 description 4
- 239000005022 packaging material Substances 0.000 description 4
- 230000035699 permeability Effects 0.000 description 4
- 229920000573 polyethylene Polymers 0.000 description 4
- CXMXRPHRNRROMY-UHFFFAOYSA-N sebacic acid Chemical compound OC(=O)CCCCCCCCC(O)=O CXMXRPHRNRROMY-UHFFFAOYSA-N 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 229960002622 triacetin Drugs 0.000 description 4
- XFRVVPUIAFSTFO-UHFFFAOYSA-N 1-Tridecanol Chemical compound CCCCCCCCCCCCCO XFRVVPUIAFSTFO-UHFFFAOYSA-N 0.000 description 3
- 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 3
- BWDBEAQIHAEVLV-UHFFFAOYSA-N 6-methylheptan-1-ol Chemical compound CC(C)CCCCCO BWDBEAQIHAEVLV-UHFFFAOYSA-N 0.000 description 3
- 208000024827 Alzheimer disease Diseases 0.000 description 3
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 3
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 3
- 239000004743 Polypropylene Substances 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 229910052782 aluminium Inorganic materials 0.000 description 3
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 3
- 238000009792 diffusion process Methods 0.000 description 3
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 3
- 238000010030 laminating Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000006116 polymerization reaction Methods 0.000 description 3
- 229920001155 polypropylene Polymers 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 229940087291 tridecyl alcohol Drugs 0.000 description 3
- 239000001069 triethyl citrate Substances 0.000 description 3
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 description 3
- 235000013769 triethyl citrate Nutrition 0.000 description 3
- GOXQRTZXKQZDDN-UHFFFAOYSA-N 2-Ethylhexyl acrylate Chemical compound CCCCC(CC)COC(=O)C=C GOXQRTZXKQZDDN-UHFFFAOYSA-N 0.000 description 2
- JYZLSYFPFQTNNO-UHFFFAOYSA-N 2-octyldecan-1-ol Chemical compound CCCCCCCCC(CO)CCCCCCCC JYZLSYFPFQTNNO-UHFFFAOYSA-N 0.000 description 2
- ANXUWUOEHBXLQO-UHFFFAOYSA-N 2-octyldodecan-1-ol Chemical compound CCCCCCCCCCC(CO)CCCCCCCC.CCCCCCCCCCC(CO)CCCCCCCC ANXUWUOEHBXLQO-UHFFFAOYSA-N 0.000 description 2
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- XFKBBSZEQRFVSL-UHFFFAOYSA-N dipropan-2-yl decanedioate Chemical compound CC(C)OC(=O)CCCCCCCCC(=O)OC(C)C XFKBBSZEQRFVSL-UHFFFAOYSA-N 0.000 description 2
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- SFFVATKALSIZGN-UHFFFAOYSA-N hexadecan-7-ol Chemical compound CCCCCCCCCC(O)CCCCCC SFFVATKALSIZGN-UHFFFAOYSA-N 0.000 description 2
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- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
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- TUNFSRHWOTWDNC-UHFFFAOYSA-N Myristic acid Natural products CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229920012485 Plasticized Polyvinyl chloride Polymers 0.000 description 1
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- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
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- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
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- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 1
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- KYIKRXIYLAGAKQ-UHFFFAOYSA-N abcn Chemical compound C1CCCCC1(C#N)N=NC1(C#N)CCCCC1 KYIKRXIYLAGAKQ-UHFFFAOYSA-N 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
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- BAPJBEWLBFYGME-UHFFFAOYSA-N acrylic acid methyl ester Natural products COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 1
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- BTFJIXJJCSYFAL-UHFFFAOYSA-N arachidyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCO BTFJIXJJCSYFAL-UHFFFAOYSA-N 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
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- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 238000002845 discoloration Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
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- GMSCBRSQMRDRCD-UHFFFAOYSA-N dodecyl 2-methylprop-2-enoate Chemical compound CCCCCCCCCCCCOC(=O)C(C)=C GMSCBRSQMRDRCD-UHFFFAOYSA-N 0.000 description 1
- 229960003135 donepezil hydrochloride Drugs 0.000 description 1
- XWAIAVWHZJNZQQ-UHFFFAOYSA-N donepezil hydrochloride Chemical compound [H+].[Cl-].O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 XWAIAVWHZJNZQQ-UHFFFAOYSA-N 0.000 description 1
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- UIWXSTHGICQLQT-UHFFFAOYSA-N ethenyl propanoate Chemical compound CCC(=O)OC=C UIWXSTHGICQLQT-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
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- 238000010528 free radical solution polymerization reaction Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229940100463 hexyl laurate Drugs 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000011256 inorganic filler Substances 0.000 description 1
- 229910003475 inorganic filler Inorganic materials 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 229940074928 isopropyl myristate Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000003475 lamination Methods 0.000 description 1
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
- 235000019359 magnesium stearate Nutrition 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
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229910001510 metal chloride Inorganic materials 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 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
- 238000002156 mixing Methods 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 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
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
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- 229920000915 polyvinyl chloride Polymers 0.000 description 1
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- 239000002244 precipitate Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- BCLQDYWZPAKKFD-UHFFFAOYSA-N propan-2-yl tetradecanoate;2-propan-2-yltetradecanoic acid Chemical compound CCCCCCCCCCCCCC(=O)OC(C)C.CCCCCCCCCCCCC(C(C)C)C(O)=O BCLQDYWZPAKKFD-UHFFFAOYSA-N 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical group O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 238000010526 radical polymerization reaction Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- DVQHRBFGRZHMSR-UHFFFAOYSA-N sodium methyl 2,2-dimethyl-4,6-dioxo-5-(N-prop-2-enoxy-C-propylcarbonimidoyl)cyclohexane-1-carboxylate Chemical compound [Na+].C=CCON=C(CCC)[C-]1C(=O)CC(C)(C)C(C(=O)OC)C1=O DVQHRBFGRZHMSR-UHFFFAOYSA-N 0.000 description 1
- 229920001935 styrene-ethylene-butadiene-styrene Polymers 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- 229940042585 tocopherol acetate Drugs 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 150000003628 tricarboxylic acids Chemical class 0.000 description 1
- 125000002889 tridecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000007740 vapor deposition Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000002759 woven fabric Substances 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
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- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
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Description
アクリル系粘着剤Aの調製を下記の要領で行なった。ドデシルメタクリレート13重量部、2−エチルヘキシルメタクリレート78重量部及び2−エチルヘキシルアクリレート9重量部を含む単量体、並びに、酢酸エチル50重量部からなる反応液を40リットルの重合機に供給し、重合機内を80℃の窒素雰囲気とした。そして、上記反応液にベンゾイルパーオキサイド0.5重量部をシクロヘキサン50重量部に溶解させてなる重合開始剤溶液を24時間かけて加えながら上記単量体を共重合させ、重合完了後に上記反応液に更に酢酸エチルを加えて、アクリル系粘着剤Aの含有量が35重量%であるアクリル系粘着剤溶液Aを得た。
2−エチルヘキシルアクリレート150重量部及びN−ビニルピロリドン50重量部を含む単量体、並びに、酢酸エチル200重量部からなる反応液をセパラブルフラスコに供給した後、このセパラブルフラスコ内を80℃の窒素雰囲気とした。そして、この反応液にベンゾイルパーオキサイド1重量部を酢酸エチル100重量部に溶解させてなる重合開始剤溶液を27時間かけて加えながら上記単量体を重合させ、重合完了後に上記反応液に更に酢酸エチルを加えて、アクリル系粘着剤Bの含有量が32重量%のアクリル系粘着剤溶液Bを得た。
ドネペジル、アクリル系粘着剤A、セバシン酸ジイソプロピル、アジピン酸ジイソプロピル、ミリスチン酸イソプロピル、2−オクチルドデカノール(2−オクチルドデカン−1−オール)及び流動パラフィンの重量組成が表1に示した割合となるように配合し、固形分の濃度が22重量%になるように酢酸エチルを加えた後、均一になるまで混合して、粘着剤層溶液を作製した。
ドネペジル、エチルセルロース(ダウケミカル社製 商品名「エトセル Premium」、粘度:7cps)、エチルセルロース(ダウケミカル社製 商品名「エトセル Premium」、粘度:100cps)、トリアセチン、クエン酸トリエチル、アジピン酸ジイソプロピル及びミリスチン酸イソプロピルの重量組成が表2に示した割合となるように配合し、固形分の濃度が25重量%になるようにエタノールを加えた後、均一になるまで混合して、リザーバ層溶液を作製した。
ドネペジル4重量%及びアクリル系粘着剤B96重量%となるように配合し、固形分の濃度が22重量%になるように酢酸エチルを加えた後、均一になるまで混合して、粘着剤層溶液を作製した。この粘着剤層溶液を用いたこと以外は比較例3と同様にして粘着剤層の厚みが100μmの貼付剤を製造した。
アクリル系粘着剤Aの代わりにアクリル系粘着剤Bを用いたこと以外は実施例11と同様にして粘着剤層の厚みが40μmの貼付剤を製造した。
製造直後の貼付剤から面積3cm2の試験片を6片切り出し、遮光した包材に密封して、3片を4℃にて、残り3片を60℃にて2週間保存した。保存後、酢酸エチルを用いて粘着剤層及びリザーバ層中のドネペジルを抽出し、HPLCを用いて粘着剤層及びリザーバ層のドネペジルの総量を定量した。4℃にて保存した試験片3片の粘着剤層及びリザーバ層中におけるドネペジルの総重量をW4、60℃にて保存した試験片3片の粘着剤層及びリザーバ層中におけるドネペジルの総重量をW60とし、下記式(1)を用いて薬物の残存率を算出した。残存率を表3の「保存安定性の含量」の欄に記載した。
残存率(重量%)=100×W60/W4・・・式(1)
製造直後の貼付剤から一辺が3cmの平面正方形状の試験片を切り出し、この試験片を遮光した包材に密封して25℃にて1カ月間に亘って保存した。1カ月後に試験片を粘着剤層側から観察して結晶の析出状態を透過型顕微鏡で40倍にて観察した。
製造直後の貼付剤から一辺が1cmの試験片を切り出す一方、37℃に保持されたFranzの拡散セルに、ヘアレスマウス(雄、8〜10週齢)の背部摘出皮膚を固定し、この皮膚の上端部に試験片をその粘着剤層によって貼付した。なお、pH7.2に調整した生理食塩水をリセプター液とし、このリセプター液中に皮膚の下端部を浸漬した。
製造直後の貼付剤から面積3cm2の試験片を15片切り出した。背部を剃毛したウサギ(雄、16〜18週齢)4羽の背部皮膚に試験片3個づつをその粘着剤層によって貼付した。残りの試験片3個を遮光した包材に密封して4℃に保存した。貼付後1日、4日、7日経過毎に、背部皮膚のそれぞれから試験片を1個づつ剥離した。各試験片の粘着剤層及びリザーバ層中のドネペジルを酢酸エチルを用いて抽出し、HPLC(high performance liquid chromatography)を用いて粘着剤層及びリザーバ層のドネペジルの総量を定量した。各試験片のドネペジルの総量を相加平均して平均値W1を算出した。4℃に保存し且つ背部皮膚に貼着していない試験片3個について、上述の測定開始から1日、4日、7日経過毎に、試験片を1個づつ取り出した。この試験片の粘着剤層及びリザーバ層中のドネペジルを酢酸エチルを用いて抽出し、HPLC(high performance liquid chromatography)を用いて粘着剤層及びリザーバ層のドネペジルの総量W0を定量した。ドネペジルの皮膚移行量を下記式に基づいて算出し、表5の「皮膚移行量」の欄に記載した。
移行量(mg)=W0−W1
2 粘着剤層
3 リザーバ層
4 中間層
5 剥離紙
Claims (2)
- 支持体、及び、この支持体の一面に積層一体化され、且つ、飽和脂肪族アルコールと(メタ)アクリル酸とのエステルを含有し且つビニルピロリドンを含有しない単量体を共重合してなる共重合体(ただし、アミノ基を有する共重合体を除く)を含有するアクリル系粘着剤と、ドネペジル又はその塩と、溶解剤とを含む粘着剤層を含み、上記溶解剤は、飽和脂肪族アルコールと飽和脂肪族カルボン酸とのジエステル及び飽和脂肪族アルコールと飽和脂肪族カルボン酸とのトリエステルからなる群から選ばれた少なくとも一種の化合物と、一価の飽和脂肪族アルコールと飽和脂肪族モノカルボン酸とのモノエステル及び一価の飽和脂肪族アルコールからなる群から選ばれた少なくとも一種の化合物とを含有していることを特徴とする貼付剤。
- 支持体と粘着剤層との間にリザーバ層が介在しており、このリザーバ層は、セルロース類と、ドネペジル又はその塩とを含有していることを特徴とする請求項1に記載の貼付剤。
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WO2019118782A1 (en) * | 2017-12-13 | 2019-06-20 | Corium, Inc. | Method for depot creation during transdermal drug delivery |
KR102565184B1 (ko) | 2018-07-09 | 2023-08-08 | 에스케이하이닉스 주식회사 | 디지털 회로를 모델링하는 회로 모듈 및 이를 포함하는 시뮬레이션 장치 |
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EP2623103A1 (en) | 2013-08-07 |
WO2012043801A1 (ja) | 2012-04-05 |
US20140141059A1 (en) | 2014-05-22 |
CN103124556A (zh) | 2013-05-29 |
CN103124556B (zh) | 2015-10-14 |
US20160128948A1 (en) | 2016-05-12 |
US20130202677A1 (en) | 2013-08-08 |
KR20140005151A (ko) | 2014-01-14 |
EP2623103A4 (en) | 2014-05-07 |
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