JP5938612B2 - 経皮吸収治療システム - Google Patents
経皮吸収治療システム Download PDFInfo
- Publication number
- JP5938612B2 JP5938612B2 JP2013107198A JP2013107198A JP5938612B2 JP 5938612 B2 JP5938612 B2 JP 5938612B2 JP 2013107198 A JP2013107198 A JP 2013107198A JP 2013107198 A JP2013107198 A JP 2013107198A JP 5938612 B2 JP5938612 B2 JP 5938612B2
- Authority
- JP
- Japan
- Prior art keywords
- tts
- rivastigmine
- layer
- active ingredient
- adhesive
- 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
Links
- 238000011282 treatment Methods 0.000 title claims description 15
- 238000010521 absorption reaction Methods 0.000 title claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 48
- XSVMFMHYUFZWBK-NSHDSACASA-N Rivastigmine Chemical compound CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 XSVMFMHYUFZWBK-NSHDSACASA-N 0.000 claims description 46
- 239000010410 layer Substances 0.000 claims description 44
- 229960004136 rivastigmine Drugs 0.000 claims description 41
- 239000000203 mixture Substances 0.000 claims description 27
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 20
- 229910052710 silicon Inorganic materials 0.000 claims description 20
- 239000010703 silicon Substances 0.000 claims description 20
- 238000009472 formulation Methods 0.000 claims description 12
- 239000012458 free base Substances 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 11
- 239000012790 adhesive layer Substances 0.000 claims description 10
- 208000024827 Alzheimer disease Diseases 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 230000001225 therapeutic effect Effects 0.000 claims description 7
- 206010012289 Dementia Diseases 0.000 claims description 5
- 238000002560 therapeutic procedure Methods 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims 1
- -1 polyethylene Polymers 0.000 description 25
- 210000003491 skin Anatomy 0.000 description 17
- 230000001070 adhesive effect Effects 0.000 description 16
- 238000000034 method Methods 0.000 description 14
- 229920000642 polymer Polymers 0.000 description 14
- 239000000853 adhesive Substances 0.000 description 13
- 238000012360 testing method Methods 0.000 description 13
- 239000013543 active substance Substances 0.000 description 12
- 230000035515 penetration Effects 0.000 description 12
- 230000036470 plasma concentration Effects 0.000 description 7
- 239000002775 capsule Substances 0.000 description 6
- 239000000544 cholinesterase inhibitor Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 238000003860 storage Methods 0.000 description 6
- 238000013270 controlled release Methods 0.000 description 5
- 239000011159 matrix material Substances 0.000 description 5
- 239000013464 silicone adhesive Substances 0.000 description 5
- 229940122041 Cholinesterase inhibitor Drugs 0.000 description 4
- 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 description 4
- 229940079593 drug Drugs 0.000 description 4
- ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 229920000139 polyethylene terephthalate Polymers 0.000 description 4
- 239000005020 polyethylene terephthalate Substances 0.000 description 4
- 238000004448 titration Methods 0.000 description 4
- RSWGJHLUYNHPMX-UHFFFAOYSA-N 1,4a-dimethyl-7-propan-2-yl-2,3,4,4b,5,6,10,10a-octahydrophenanthrene-1-carboxylic acid Chemical class C12CCC(C(C)C)=CC2=CCC2C1(C)CCCC2(C)C(O)=O RSWGJHLUYNHPMX-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 239000004698 Polyethylene Substances 0.000 description 3
- 239000004743 Polypropylene Substances 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 230000003444 anaesthetic effect Effects 0.000 description 3
- 239000002220 antihypertensive agent Substances 0.000 description 3
- 229940030600 antihypertensive agent Drugs 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 3
- 239000003963 antioxidant agent Substances 0.000 description 3
- 235000006708 antioxidants Nutrition 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 229940127089 cytotoxic agent Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 229940108366 exelon Drugs 0.000 description 3
- 230000002496 gastric effect Effects 0.000 description 3
- 229920000058 polyacrylate Polymers 0.000 description 3
- 229920000573 polyethylene Polymers 0.000 description 3
- 229920001155 polypropylene Polymers 0.000 description 3
- 229920005573 silicon-containing polymer Polymers 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- RDJGLLICXDHJDY-NSHDSACASA-N (2s)-2-(3-phenoxyphenyl)propanoic acid Chemical compound OC(=O)[C@@H](C)C1=CC=CC(OC=2C=CC=CC=2)=C1 RDJGLLICXDHJDY-NSHDSACASA-N 0.000 description 2
- RLFWWDJHLFCNIJ-UHFFFAOYSA-N Aminoantipyrine Natural products CN1C(C)=C(N)C(=O)N1C1=CC=CC=C1 RLFWWDJHLFCNIJ-UHFFFAOYSA-N 0.000 description 2
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
- 239000004322 Butylated hydroxytoluene Substances 0.000 description 2
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-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
- 241000282412 Homo Species 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 208000018737 Parkinson disease Diseases 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 2
- 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 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 239000000150 Sympathomimetic Substances 0.000 description 2
- ZZHLYYDVIOPZBE-UHFFFAOYSA-N Trimeprazine Chemical compound C1=CC=C2N(CC(CN(C)C)C)C3=CC=CC=C3SC2=C1 ZZHLYYDVIOPZBE-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000000202 analgesic effect Effects 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 239000000935 antidepressant agent Substances 0.000 description 2
- 229940005513 antidepressants Drugs 0.000 description 2
- 239000000739 antihistaminic agent Substances 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 239000012620 biological material Substances 0.000 description 2
- 210000001124 body fluid Anatomy 0.000 description 2
- 239000010839 body fluid Substances 0.000 description 2
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 2
- 229940095259 butylated hydroxytoluene Drugs 0.000 description 2
- 229940097217 cardiac glycoside Drugs 0.000 description 2
- 239000002368 cardiac glycoside Substances 0.000 description 2
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 238000009792 diffusion process Methods 0.000 description 2
- 239000004205 dimethyl polysiloxane Substances 0.000 description 2
- 229960003530 donepezil Drugs 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 229960001419 fenoprofen Drugs 0.000 description 2
- 229960003980 galantamine Drugs 0.000 description 2
- ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 229960004640 memantine Drugs 0.000 description 2
- BUGYDGFZZOZRHP-UHFFFAOYSA-N memantine Chemical compound C1C(C2)CC3(C)CC1(C)CC2(N)C3 BUGYDGFZZOZRHP-UHFFFAOYSA-N 0.000 description 2
- 239000002664 nootropic agent Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- CPJSUEIXXCENMM-UHFFFAOYSA-N phenacetin Chemical compound CCOC1=CC=C(NC(C)=O)C=C1 CPJSUEIXXCENMM-UHFFFAOYSA-N 0.000 description 2
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 2
- 229920001296 polysiloxane Polymers 0.000 description 2
- 230000001003 psychopharmacologic effect Effects 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 229930002534 steroid glycoside Natural products 0.000 description 2
- 150000008143 steroidal glycosides Chemical class 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 230000001975 sympathomimetic effect Effects 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 235000015961 tonic Nutrition 0.000 description 2
- 230000001256 tonic effect Effects 0.000 description 2
- 229960000716 tonics Drugs 0.000 description 2
- 239000003204 tranquilizing agent Substances 0.000 description 2
- 230000002936 tranquilizing effect Effects 0.000 description 2
- 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 2
- 239000000814 tuberculostatic agent Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 2
- CEMAWMOMDPGJMB-UHFFFAOYSA-N (+-)-Oxprenolol Chemical compound CC(C)NCC(O)COC1=CC=CC=C1OCC=C CEMAWMOMDPGJMB-UHFFFAOYSA-N 0.000 description 1
- MDKGKXOCJGEUJW-VIFPVBQESA-N (2s)-2-[4-(thiophene-2-carbonyl)phenyl]propanoic acid Chemical compound C1=CC([C@@H](C(O)=O)C)=CC=C1C(=O)C1=CC=CS1 MDKGKXOCJGEUJW-VIFPVBQESA-N 0.000 description 1
- 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
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
- 229930182837 (R)-adrenaline Natural products 0.000 description 1
- AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical compound CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-UHFFFAOYSA-N 0.000 description 1
- DVSLBDBGAXXLKZ-UHFFFAOYSA-N 2,3-diethylbenzamide Chemical compound CCC1=CC=CC(C(N)=O)=C1CC DVSLBDBGAXXLKZ-UHFFFAOYSA-N 0.000 description 1
- LRXFKKPEBXIPMW-UHFFFAOYSA-N 2-(9h-fluoren-2-yl)propanoic acid Chemical compound C1=CC=C2C3=CC=C(C(C(O)=O)C)C=C3CC2=C1 LRXFKKPEBXIPMW-UHFFFAOYSA-N 0.000 description 1
- APBSKHYXXKHJFK-UHFFFAOYSA-N 2-[2-(4-chlorophenyl)-1,3-thiazol-4-yl]acetic acid Chemical compound OC(=O)CC1=CSC(C=2C=CC(Cl)=CC=2)=N1 APBSKHYXXKHJFK-UHFFFAOYSA-N 0.000 description 1
- YNZFUWZUGRBMHL-UHFFFAOYSA-N 2-[4-[3-(11-benzo[b][1]benzazepinyl)propyl]-1-piperazinyl]ethanol Chemical compound C1CN(CCO)CCN1CCCN1C2=CC=CC=C2C=CC2=CC=CC=C21 YNZFUWZUGRBMHL-UHFFFAOYSA-N 0.000 description 1
- PJJGZPJJTHBVMX-UHFFFAOYSA-N 5,7-Dihydroxyisoflavone Chemical compound C=1C(O)=CC(O)=C(C2=O)C=1OC=C2C1=CC=CC=C1 PJJGZPJJTHBVMX-UHFFFAOYSA-N 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 102100033639 Acetylcholinesterase Human genes 0.000 description 1
- 108010022752 Acetylcholinesterase Proteins 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- RMMXTBMQSGEXHJ-UHFFFAOYSA-N Aminophenazone Chemical compound O=C1C(N(C)C)=C(C)N(C)N1C1=CC=CC=C1 RMMXTBMQSGEXHJ-UHFFFAOYSA-N 0.000 description 1
- 108010001478 Bacitracin Proteins 0.000 description 1
- 208000034332 Body integrity dysphoria Diseases 0.000 description 1
- 108010053652 Butyrylcholinesterase Proteins 0.000 description 1
- GNWUOVJNSFPWDD-XMZRARIVSA-M Cefoxitin sodium Chemical compound [Na+].N([C@]1(OC)C(N2C(=C(COC(N)=O)CS[C@@H]21)C([O-])=O)=O)C(=O)CC1=CC=CS1 GNWUOVJNSFPWDD-XMZRARIVSA-M 0.000 description 1
- 102100032404 Cholinesterase Human genes 0.000 description 1
- 235000001258 Cinchona calisaya Nutrition 0.000 description 1
- GDLIGKIOYRNHDA-UHFFFAOYSA-N Clomipramine Chemical compound C1CC2=CC=C(Cl)C=C2N(CCCN(C)C)C2=CC=CC=C21 GDLIGKIOYRNHDA-UHFFFAOYSA-N 0.000 description 1
- 208000031124 Dementia Alzheimer type Diseases 0.000 description 1
- 101000783577 Dendroaspis angusticeps Thrombostatin Proteins 0.000 description 1
- 101000783578 Dendroaspis jamesoni kaimosae Dendroaspin Proteins 0.000 description 1
- HCYAFALTSJYZDH-UHFFFAOYSA-N Desimpramine Chemical compound C1CC2=CC=CC=C2N(CCCNC)C2=CC=CC=C21 HCYAFALTSJYZDH-UHFFFAOYSA-N 0.000 description 1
- WDJUZGPOPHTGOT-OAXVISGBSA-N Digitoxin Natural products O([C@H]1[C@@H](C)O[C@@H](O[C@@H]2C[C@@H]3[C@@](C)([C@@H]4[C@H]([C@]5(O)[C@@](C)([C@H](C6=CC(=O)OC6)CC5)CC4)CC3)CC2)C[C@H]1O)[C@H]1O[C@@H](C)[C@H](O[C@H]2O[C@@H](C)[C@@H](O)[C@@H](O)C2)[C@@H](O)C1 WDJUZGPOPHTGOT-OAXVISGBSA-N 0.000 description 1
- LTMHDMANZUZIPE-AMTYYWEZSA-N Digoxin Natural products O([C@H]1[C@H](C)O[C@H](O[C@@H]2C[C@@H]3[C@@](C)([C@@H]4[C@H]([C@]5(O)[C@](C)([C@H](O)C4)[C@H](C4=CC(=O)OC4)CC5)CC3)CC2)C[C@@H]1O)[C@H]1O[C@H](C)[C@@H](O[C@H]2O[C@@H](C)[C@H](O)[C@@H](O)C2)[C@@H](O)C1 LTMHDMANZUZIPE-AMTYYWEZSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 108090000371 Esterases Proteins 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 108010026389 Gramicidin Proteins 0.000 description 1
- ZRJBHWIHUMBLCN-SEQYCRGISA-N Huperzine A Natural products N1C(=O)C=CC2=C1C[C@H]1/C(=C/C)[C@]2(N)CC(C)=C1 ZRJBHWIHUMBLCN-SEQYCRGISA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- PWWVAXIEGOYWEE-UHFFFAOYSA-N Isophenergan Chemical compound C1=CC=C2N(CC(C)N(C)C)C3=CC=CC=C3SC2=C1 PWWVAXIEGOYWEE-UHFFFAOYSA-N 0.000 description 1
- 239000011786 L-ascorbyl-6-palmitate Substances 0.000 description 1
- QAQJMLQRFWZOBN-LAUBAEHRSA-N L-ascorbyl-6-palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-LAUBAEHRSA-N 0.000 description 1
- 102000009151 Luteinizing Hormone Human genes 0.000 description 1
- 108010073521 Luteinizing Hormone Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- SBDNJUWAMKYJOX-UHFFFAOYSA-N Meclofenamic Acid Chemical compound CC1=CC=C(Cl)C(NC=2C(=CC=CC=2)C(O)=O)=C1Cl SBDNJUWAMKYJOX-UHFFFAOYSA-N 0.000 description 1
- 229920000877 Melamine resin Polymers 0.000 description 1
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- JZFPYUNJRRFVQU-UHFFFAOYSA-N Niflumic acid Chemical compound OC(=O)C1=CC=CN=C1NC1=CC=CC(C(F)(F)F)=C1 JZFPYUNJRRFVQU-UHFFFAOYSA-N 0.000 description 1
- PHVGLTMQBUFIQQ-UHFFFAOYSA-N Nortryptiline Chemical compound C1CC2=CC=CC=C2C(=CCCNC)C2=CC=CC=C21 PHVGLTMQBUFIQQ-UHFFFAOYSA-N 0.000 description 1
- 239000004100 Oxytetracycline Substances 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
- PIJVFDBKTWXHHD-UHFFFAOYSA-N Physostigmine Natural products C12=CC(OC(=O)NC)=CC=C2N(C)C2C1(C)CCN2C PIJVFDBKTWXHHD-UHFFFAOYSA-N 0.000 description 1
- 229920002367 Polyisobutene Polymers 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
- ZRJBHWIHUMBLCN-UHFFFAOYSA-N Shuangyiping Natural products N1C(=O)C=CC2=C1CC1C(=CC)C2(N)CC(C)=C1 ZRJBHWIHUMBLCN-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- NHUHCSRWZMLRLA-UHFFFAOYSA-N Sulfisoxazole Chemical compound CC1=NOC(NS(=O)(=O)C=2C=CC(N)=CC=2)=C1C NHUHCSRWZMLRLA-UHFFFAOYSA-N 0.000 description 1
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- KLBQZWRITKRQQV-UHFFFAOYSA-N Thioridazine Chemical compound C12=CC(SC)=CC=C2SC2=CC=CC=C2N1CCC1CCCCN1C KLBQZWRITKRQQV-UHFFFAOYSA-N 0.000 description 1
- 208000030886 Traumatic Brain injury Diseases 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 239000002998 adhesive polymer Substances 0.000 description 1
- 239000000695 adrenergic alpha-agonist Substances 0.000 description 1
- 239000000808 adrenergic beta-agonist Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 229960003790 alimemazine Drugs 0.000 description 1
- 102000004305 alpha Adrenergic Receptors Human genes 0.000 description 1
- 108090000861 alpha Adrenergic Receptors Proteins 0.000 description 1
- 229940087168 alpha tocopherol Drugs 0.000 description 1
- 229960000212 aminophenazone Drugs 0.000 description 1
- YZQNFFLGIYEXMM-UHFFFAOYSA-N aminopromazine Chemical compound C1=CC=C2N(CC(CN(C)C)N(C)C)C3=CC=CC=C3SC2=C1 YZQNFFLGIYEXMM-UHFFFAOYSA-N 0.000 description 1
- 229950005325 aminopromazine Drugs 0.000 description 1
- 229960000836 amitriptyline Drugs 0.000 description 1
- KRMDCWKBEZIMAB-UHFFFAOYSA-N amitriptyline Chemical compound C1CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 KRMDCWKBEZIMAB-UHFFFAOYSA-N 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003098 androgen Substances 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000002280 anti-androgenic effect Effects 0.000 description 1
- 239000004004 anti-anginal agent Substances 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 230000002921 anti-spasmodic effect Effects 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 239000000043 antiallergic agent Substances 0.000 description 1
- 239000000051 antiandrogen Substances 0.000 description 1
- 229940124345 antianginal agent Drugs 0.000 description 1
- 239000003416 antiarrhythmic agent Substances 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 229940125682 antidementia agent Drugs 0.000 description 1
- 229940125708 antidiabetic agent Drugs 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 229940125684 antimigraine agent Drugs 0.000 description 1
- 239000002282 antimigraine agent Substances 0.000 description 1
- 229940125688 antiparkinson agent Drugs 0.000 description 1
- 239000000939 antiparkinson agent Substances 0.000 description 1
- 229940127218 antiplatelet drug Drugs 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 229940125716 antipyretic agent Drugs 0.000 description 1
- VEQOALNAAJBPNY-UHFFFAOYSA-N antipyrine Chemical compound CN1C(C)=CC(=O)N1C1=CC=CC=C1 VEQOALNAAJBPNY-UHFFFAOYSA-N 0.000 description 1
- 239000003435 antirheumatic agent Substances 0.000 description 1
- 239000003420 antiserotonin agent Substances 0.000 description 1
- 229940124575 antispasmodic agent Drugs 0.000 description 1
- 229960004676 antithrombotic agent Drugs 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 239000000823 artificial membrane Substances 0.000 description 1
- 230000001174 ascending effect Effects 0.000 description 1
- 235000010385 ascorbyl palmitate Nutrition 0.000 description 1
- 229960003071 bacitracin Drugs 0.000 description 1
- 229930184125 bacitracin Natural products 0.000 description 1
- CLKOFPXJLQSYAH-ABRJDSQDSA-N bacitracin A Chemical compound C1SC([C@@H](N)[C@@H](C)CC)=N[C@@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]1C(=O)N[C@H](CCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2N=CNC=2)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)NCCCC1 CLKOFPXJLQSYAH-ABRJDSQDSA-N 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 229940124630 bronchodilator Drugs 0.000 description 1
- 230000001813 broncholytic effect Effects 0.000 description 1
- CDQSJQSWAWPGKG-UHFFFAOYSA-N butane-1,1-diol Chemical compound CCCC(O)O CDQSJQSWAWPGKG-UHFFFAOYSA-N 0.000 description 1
- 239000007963 capsule composition Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 239000000496 cardiotonic agent Substances 0.000 description 1
- 239000002327 cardiovascular agent Substances 0.000 description 1
- 229940125692 cardiovascular agent Drugs 0.000 description 1
- 229960003184 carprofen Drugs 0.000 description 1
- IVUMCTKHWDRRMH-UHFFFAOYSA-N carprofen Chemical compound C1=CC(Cl)=C[C]2C3=CC=C(C(C(O)=O)C)C=C3N=C21 IVUMCTKHWDRRMH-UHFFFAOYSA-N 0.000 description 1
- 229960001139 cefazolin Drugs 0.000 description 1
- MLYYVTUWGNIJIB-BXKDBHETSA-N cefazolin Chemical compound S1C(C)=NN=C1SCC1=C(C(O)=O)N2C(=O)[C@@H](NC(=O)CN3N=NN=C3)[C@H]2SC1 MLYYVTUWGNIJIB-BXKDBHETSA-N 0.000 description 1
- 229960002682 cefoxitin Drugs 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- RNFNDJAIBTYOQL-UHFFFAOYSA-N chloral hydrate Chemical compound OC(O)C(Cl)(Cl)Cl RNFNDJAIBTYOQL-UHFFFAOYSA-N 0.000 description 1
- 229960002327 chloral hydrate Drugs 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
- CYDMQBQPVICBEU-UHFFFAOYSA-N chlorotetracycline Natural products C1=CC(Cl)=C2C(O)(C)C3CC4C(N(C)C)C(O)=C(C(N)=O)C(=O)C4(O)C(O)=C3C(=O)C2=C1O CYDMQBQPVICBEU-UHFFFAOYSA-N 0.000 description 1
- 229960001076 chlorpromazine Drugs 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
- CYDMQBQPVICBEU-XRNKAMNCSA-N chlortetracycline Chemical compound C1=CC(Cl)=C2[C@](O)(C)[C@H]3C[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 CYDMQBQPVICBEU-XRNKAMNCSA-N 0.000 description 1
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 1
- 229960004606 clomipramine Drugs 0.000 description 1
- CLOMYZFHNHFSIQ-UHFFFAOYSA-N clonixin Chemical compound CC1=C(Cl)C=CC=C1NC1=NC=CC=C1C(O)=O CLOMYZFHNHFSIQ-UHFFFAOYSA-N 0.000 description 1
- 229960001209 clonixin Drugs 0.000 description 1
- 229960004126 codeine Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000003218 coronary vasodilator agent Substances 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 230000001085 cytostatic effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 229960003914 desipramine Drugs 0.000 description 1
- 229960001259 diclofenac Drugs 0.000 description 1
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 1
- XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 description 1
- 229960000648 digitoxin Drugs 0.000 description 1
- WDJUZGPOPHTGOT-XUDUSOBPSA-N digitoxin Chemical compound C1[C@H](O)[C@H](O)[C@@H](C)O[C@H]1O[C@@H]1[C@@H](C)O[C@@H](O[C@@H]2[C@H](O[C@@H](O[C@@H]3C[C@@H]4[C@]([C@@H]5[C@H]([C@]6(CC[C@@H]([C@@]6(C)CC5)C=5COC(=O)C=5)O)CC4)(C)CC3)C[C@@H]2O)C)C[C@@H]1O WDJUZGPOPHTGOT-XUDUSOBPSA-N 0.000 description 1
- 229960005156 digoxin Drugs 0.000 description 1
- LTMHDMANZUZIPE-PUGKRICDSA-N digoxin Chemical compound C1[C@H](O)[C@H](O)[C@@H](C)O[C@H]1O[C@@H]1[C@@H](C)O[C@@H](O[C@@H]2[C@H](O[C@@H](O[C@@H]3C[C@@H]4[C@]([C@@H]5[C@H]([C@]6(CC[C@@H]([C@@]6(C)[C@H](O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)C[C@@H]2O)C)C[C@@H]1O LTMHDMANZUZIPE-PUGKRICDSA-N 0.000 description 1
- LTMHDMANZUZIPE-UHFFFAOYSA-N digoxine Natural products C1C(O)C(O)C(C)OC1OC1C(C)OC(OC2C(OC(OC3CC4C(C5C(C6(CCC(C6(C)C(O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)CC2O)C)CC1O LTMHDMANZUZIPE-UHFFFAOYSA-N 0.000 description 1
- 238000007922 dissolution test Methods 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 229940030606 diuretics Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000008451 emotion Effects 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- 229960003133 ergot alkaloid Drugs 0.000 description 1
- 229960003276 erythromycin Drugs 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 229960005293 etodolac Drugs 0.000 description 1
- XFBVBWWRPKNWHW-UHFFFAOYSA-N etodolac Chemical compound C1COC(CC)(CC(O)=O)C2=N[C]3C(CC)=CC=CC3=C21 XFBVBWWRPKNWHW-UHFFFAOYSA-N 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 229950011481 fenclozic acid Drugs 0.000 description 1
- 238000010579 first pass effect Methods 0.000 description 1
- LPEPZBJOKDYZAD-UHFFFAOYSA-N flufenamic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=CC(C(F)(F)F)=C1 LPEPZBJOKDYZAD-UHFFFAOYSA-N 0.000 description 1
- 229960004369 flufenamic acid Drugs 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229960002390 flurbiprofen Drugs 0.000 description 1
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 229960004905 gramicidin Drugs 0.000 description 1
- ZWCXYZRRTRDGQE-SORVKSEFSA-N gramicidina Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](C(C)C)NC(=O)[C@H](C)NC(=O)[C@H](NC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H](NC=O)C(C)C)CC(C)C)C(=O)NCCO)=CNC2=C1 ZWCXYZRRTRDGQE-SORVKSEFSA-N 0.000 description 1
- 210000003780 hair follicle Anatomy 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- ZRJBHWIHUMBLCN-YQEJDHNASA-N huperzine A Chemical compound N1C(=O)C=CC2=C1C[C@H]1\C(=C/C)[C@]2(N)CC(C)=C1 ZRJBHWIHUMBLCN-YQEJDHNASA-N 0.000 description 1
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 239000005554 hypnotics and sedatives Substances 0.000 description 1
- 229950009183 ibufenac Drugs 0.000 description 1
- CYWFCPPBTWOZSF-UHFFFAOYSA-N ibufenac Chemical compound CC(C)CC1=CC=C(CC(O)=O)C=C1 CYWFCPPBTWOZSF-UHFFFAOYSA-N 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 229960004801 imipramine Drugs 0.000 description 1
- BCGWQEUPMDMJNV-UHFFFAOYSA-N imipramine Chemical compound C1CC2=CC=CC=C2N(CCCN(C)C)C2=CC=CC=C21 BCGWQEUPMDMJNV-UHFFFAOYSA-N 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 description 1
- 229960000991 ketoprofen Drugs 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 229940040129 luteinizing hormone Drugs 0.000 description 1
- 229960004090 maprotiline Drugs 0.000 description 1
- QSLMDECMDJKHMQ-GSXCWMCISA-N maprotiline Chemical compound C12=CC=CC=C2[C@@]2(CCCNC)C3=CC=CC=C3[C@@H]1CC2 QSLMDECMDJKHMQ-GSXCWMCISA-N 0.000 description 1
- 229960003803 meclofenamic acid Drugs 0.000 description 1
- 229960003464 mefenamic acid Drugs 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- OVXRPXGVKBHGQO-UYWIDEMCSA-N methyl (1r,4ar,4br,10ar)-1,4a-dimethyl-7-propan-2-yl-2,3,4,4b,5,6,10,10a-octahydrophenanthrene-1-carboxylate Chemical class C1CC(C(C)C)=CC2=CC[C@H]3[C@@](C(=O)OC)(C)CCC[C@]3(C)[C@H]21 OVXRPXGVKBHGQO-UYWIDEMCSA-N 0.000 description 1
- IUBSYMUCCVWXPE-UHFFFAOYSA-N metoprolol Chemical compound COCCC1=CC=C(OCC(O)CNC(C)C)C=C1 IUBSYMUCCVWXPE-UHFFFAOYSA-N 0.000 description 1
- 229960002237 metoprolol Drugs 0.000 description 1
- GCIGZRAXWDUHRE-UHFFFAOYSA-N n-(1,5-dimethyl-3-oxo-2-phenylpyrazol-4-yl)-n-methylpyridine-3-carboxamide Chemical compound CC=1N(C)N(C=2C=CC=CC=2)C(=O)C=1N(C)C(=O)C1=CC=CN=C1 GCIGZRAXWDUHRE-UHFFFAOYSA-N 0.000 description 1
- 229960002009 naproxen Drugs 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 229960000916 niflumic acid Drugs 0.000 description 1
- 230000001777 nootropic effect Effects 0.000 description 1
- 229960001158 nortriptyline Drugs 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
- 229960005290 opipramol Drugs 0.000 description 1
- 229960002739 oxaprozin Drugs 0.000 description 1
- OFPXSFXSNFPTHF-UHFFFAOYSA-N oxaprozin Chemical compound O1C(CCC(=O)O)=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 OFPXSFXSNFPTHF-UHFFFAOYSA-N 0.000 description 1
- 229960004570 oxprenolol Drugs 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
- GHZNWXGYWUBLLI-UHFFFAOYSA-N p-Lactophenetide Chemical compound CCOC1=CC=C(NC(=O)C(C)O)C=C1 GHZNWXGYWUBLLI-UHFFFAOYSA-N 0.000 description 1
- 229960005489 paracetamol Drugs 0.000 description 1
- CBHCDHNUZWWAPP-UHFFFAOYSA-N pecazine Chemical compound C1N(C)CCCC1CN1C2=CC=CC=C2SC2=CC=CC=C21 CBHCDHNUZWWAPP-UHFFFAOYSA-N 0.000 description 1
- 229950007538 pecazine Drugs 0.000 description 1
- 239000003961 penetration enhancing agent Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 150000002960 penicillins Chemical class 0.000 description 1
- VOKSWYLNZZRQPF-GDIGMMSISA-N pentazocine Chemical compound C1C2=CC=C(O)C=C2[C@@]2(C)[C@@H](C)[C@@H]1N(CC=C(C)C)CC2 VOKSWYLNZZRQPF-GDIGMMSISA-N 0.000 description 1
- 229960005301 pentazocine Drugs 0.000 description 1
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 229960003893 phenacetin Drugs 0.000 description 1
- 229960005222 phenazone Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- PIJVFDBKTWXHHD-HIFRSBDPSA-N physostigmine Chemical compound C12=CC(OC(=O)NC)=CC=C2N(C)[C@@H]2[C@@]1(C)CCN2C PIJVFDBKTWXHHD-HIFRSBDPSA-N 0.000 description 1
- 229960001697 physostigmine Drugs 0.000 description 1
- 239000000106 platelet aggregation inhibitor Substances 0.000 description 1
- 229920001083 polybutene Polymers 0.000 description 1
- 229920000346 polystyrene-polyisoprene block-polystyrene Polymers 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 229960003910 promethazine Drugs 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- PXWLVJLKJGVOKE-UHFFFAOYSA-N propyphenazone Chemical compound O=C1C(C(C)C)=C(C)N(C)N1C1=CC=CC=C1 PXWLVJLKJGVOKE-UHFFFAOYSA-N 0.000 description 1
- 229960002189 propyphenazone Drugs 0.000 description 1
- 239000011241 protective layer Substances 0.000 description 1
- 238000004080 punching Methods 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 229960000948 quinine Drugs 0.000 description 1
- ZRJBHWIHUMBLCN-BMIGLBTASA-N rac-huperzine A Natural products N1C(=O)C=CC2=C1C[C@@H]1C(=CC)[C@@]2(N)CC(C)=C1 ZRJBHWIHUMBLCN-BMIGLBTASA-N 0.000 description 1
- 239000003087 receptor blocking agent Substances 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
- 229960001225 rifampicin Drugs 0.000 description 1
- JQXXHWHPUNPDRT-WLSIYKJHSA-N rifampicin Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(C)/C(=O)NC=2C(O)=C3C([O-])=C4C)C)OC)C4=C1C3=C(O)C=2\C=N\N1CC[NH+](C)CC1 JQXXHWHPUNPDRT-WLSIYKJHSA-N 0.000 description 1
- 229950010673 rivastigmine hydrogen tartrate Drugs 0.000 description 1
- 229960004323 rivastigmine tartrate Drugs 0.000 description 1
- GWHQHAUAXRMMOT-MBANBULQSA-N rivastigmine tartrate Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 GWHQHAUAXRMMOT-MBANBULQSA-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
- 238000005070 sampling Methods 0.000 description 1
- KQPKPCNLIDLUMF-UHFFFAOYSA-N secobarbital Chemical compound CCCC(C)C1(CC=C)C(=O)NC(=O)NC1=O KQPKPCNLIDLUMF-UHFFFAOYSA-N 0.000 description 1
- 229960002060 secobarbital Drugs 0.000 description 1
- MEZLKOACVSPNER-GFCCVEGCSA-N selegiline Chemical compound C#CCN(C)[C@H](C)CC1=CC=CC=C1 MEZLKOACVSPNER-GFCCVEGCSA-N 0.000 description 1
- 229960003946 selegiline Drugs 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000000021 stimulant Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 210000003699 striated muscle Anatomy 0.000 description 1
- 229960000654 sulfafurazole Drugs 0.000 description 1
- 229960002597 sulfamerazine Drugs 0.000 description 1
- QPPBRPIAZZHUNT-UHFFFAOYSA-N sulfamerazine Chemical compound CC1=CC=NC(NS(=O)(=O)C=2C=CC(N)=CC=2)=N1 QPPBRPIAZZHUNT-UHFFFAOYSA-N 0.000 description 1
- ASWVTGNCAZCNNR-UHFFFAOYSA-N sulfamethazine Chemical compound CC1=CC(C)=NC(NS(=O)(=O)C=2C=CC(N)=CC=2)=N1 ASWVTGNCAZCNNR-UHFFFAOYSA-N 0.000 description 1
- 229960005158 sulfamethizole Drugs 0.000 description 1
- VACCAVUAMIDAGB-UHFFFAOYSA-N sulfamethizole Chemical compound S1C(C)=NN=C1NS(=O)(=O)C1=CC=C(N)C=C1 VACCAVUAMIDAGB-UHFFFAOYSA-N 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 229960000894 sulindac Drugs 0.000 description 1
- MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 description 1
- 229960004492 suprofen Drugs 0.000 description 1
- 229940064707 sympathomimetics Drugs 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 229960001685 tacrine Drugs 0.000 description 1
- YLJREFDVOIBQDA-UHFFFAOYSA-N tacrine Chemical compound C1=CC=C2C(N)=C(CCCC3)C3=NC2=C1 YLJREFDVOIBQDA-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
- IMCGHZIGRANKHV-AJNGGQMLSA-N tert-butyl (3s,5s)-2-oxo-5-[(2s,4s)-5-oxo-4-propan-2-yloxolan-2-yl]-3-propan-2-ylpyrrolidine-1-carboxylate Chemical compound O1C(=O)[C@H](C(C)C)C[C@H]1[C@H]1N(C(=O)OC(C)(C)C)C(=O)[C@H](C(C)C)C1 IMCGHZIGRANKHV-AJNGGQMLSA-N 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 229960002784 thioridazine Drugs 0.000 description 1
- 229960000984 tocofersolan Drugs 0.000 description 1
- YEZNLOUZAIOMLT-UHFFFAOYSA-N tolfenamic acid Chemical compound CC1=C(Cl)C=CC=C1NC1=CC=CC=C1C(O)=O YEZNLOUZAIOMLT-UHFFFAOYSA-N 0.000 description 1
- 229960002905 tolfenamic acid Drugs 0.000 description 1
- 230000009529 traumatic brain injury Effects 0.000 description 1
- 229960003904 triflupromazine Drugs 0.000 description 1
- XSCGXQMFQXDFCW-UHFFFAOYSA-N triflupromazine Chemical compound C1=C(C(F)(F)F)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 XSCGXQMFQXDFCW-UHFFFAOYSA-N 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
- 235000004835 α-tocopherol Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
- A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
- A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
- A61K9/7069—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained otherwise than by reactions only involving carbon to carbon unsaturated bonds, e.g. polysiloxane, polyesters, polyurethane, polyethylene oxide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
- A61K9/7084—Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/27—Esters, e.g. nitroglycerine, selenocyanates of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
- A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
- A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
- A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
- A61K9/7061—Polyacrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Dermatology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Emergency Medicine (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Psychology (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Description
用語“経皮吸収治療システム”は、薬学的活性成分を皮膚を通して放出できる全てのデバイスを意味する。これは、特にパッチのような自己接着性デバイスを含む。
好ましくは、活性成分は抗認知症剤、例えばリバスチグミン、ドネペジル、ガランタミン、セレギリン、メマンチン(memanitine)および該活性成分の薬理学的に許容される塩から成る群から選択する。
好ましいのは、活性成分としてリバスチグミンおよびメマンチンの組合せである。
用語“シリコンポリマー”は、ポリジメチルシロキサンベースのポリマー、例えばDow Corningからのアミノコンパチブル(aminocompatible)Bio-PSA Q7-4302を意味する。
a.)活性成分の接着剤溶液を製造し
b.)活性成分の接着剤溶液をコーティングし
c.)活性成分の接着剤溶液を乾燥させ
d.)シリコン接着剤溶液を製造し
e.)シリコン接着剤溶液をコーティングし
f.)シリコン接着層を接着層中の薬剤に重層し
g.)押し抜きし、袋詰めする
工程を含む。
・第一および/または第二成分の組成、例えば、賦形剤および/または活性剤(複数もある)の性質および量
・接着層のタイプ
・パッチの寸法
を変えることにより得ることができることを認識する。
・活性剤の放出までの時間(ラグタイムまたは遅延時間)
・活性剤の放出速度(速いまたは遅い)
・活性剤の放出時間(長いまたは短い)
・初回通過代謝の減少
・患者のコンプライアンスの改善
・投与間隔の減少
以下の非限定的実施例は、本発明を説明する:
以下の例示的試験は、その遊離塩基形で存在するコリンエステラーゼ阻害剤リバスチグミンを使用して行った。試験のために、以下の2種のTTSを製造した:
TTS#1:以下の組成を有する60g/m2の単位面積当たりの重量の支持体部分を製造した:
両方のTTSの接着力を当業者に既知の方法により、以下の細目を考慮して決定した:
− 支持体部分サイズ:10cm2
− テストプレート:鋼
− 剥がす角度:90°
− 剥がす速度:300mm/分
両方のTTSについて、図1にしめす接着力が得られた。図1のチャートは、シリコン接着層でのアクリレート接着剤マトリックスのコーティングが、その接着力を顕著に増加させることを明らかに示す。
その遊離塩基の形のリバスチグミンは室温で液体である。故に、30重量%の活性成分を包含させるとき“濃化ポリマー”(Plastoid(登録商標)B)の添加が必要であった。故に、低接着力の支持体となる。付加的シリコン接着層を使用したとき、接着力は、付加的シリコン接着層がない同等なTTSの約5倍である。
付加的シリコン接着層の適用が活性成分放出に影響するか否かを測定するため、全層ヒト皮膚およびEVA膜を通したリバスチグミンの浸透を両TTSで試験した。該浸透試験のために、以下の条件を適用した:
全層ヒト皮膚およびEVA膜を、各々改変Franz拡散セルに入れた。拡散表面面積は1.51cm2であった。0.1%ナトリウムアジド含有リン酸緩衝液(pH5.5)をアクセプター媒体として使用した。本アクセプター媒体は9mlの容量であった。試験温度を水浴の手段により32℃に調節し、故に、インビボヒト皮膚の温度に対応した。
全アクセプター媒体を、全試験期間を通して完全なシンク条件を確実にするために、8、24、32、48、56および72時間後に新鮮なアクセプター溶液に変えた。
アクセプター媒体中のリバスチグミン濃度をHPLCで測定した。
浸透試験の結果を図2および3にグラフ的に示す。
該結果は、その遊離塩基で存在するリバスチグミンのヒト皮膚を通る浸透速度が、2種のTTSで実質的に差がないことを説明する(図2)。わずかな変動は、皮膚のような生物学的材料のためであるように見え、例えば、例えば微小病巣または毛嚢のような皮膚の変化により説明できる。
生物学的材料の使用が原因の変動を排除するため、浸透試験を人工膜(EVA膜)を使用して繰り返した。図3に示す結果は、全層ヒト皮膚で得られた発見、すなわち、両方のTTSがそれらの浸透特性に関して差異がないことを確認する。
驚くべきことに、付加的シリコン接着層の付加は、皮膚を通る活性成分浸透に影響しなかった。
本発明によって、それ故に、元々のサイズを維持しながら顕著に高い接着力を有するTTSが製造できる。
軽度から中程度アルツハイマー病患者での、定常状態でのTTS#2 5cm2、10cm2、15cm2、および20cm2および1.5mg、3mg、4.5mg、および6mg BID Exelon(登録商標)カプセル剤を評価するオープンラベル、平衡群、4期間、上行性用量比例試験を行った。
軽度から中程度アルツハイマー病と診断された患者を、TTS#2またはカプセル剤処置のいずれかに無作為化した。包含基準は:アルツハイマー型認知症の(DSM-IV)基準を満たす、年齢50−85歳の、男性または女性(妊娠の可能性がない)患者であった。患者は、NINCDS-ADRDA基準に従い、10−26(両端を含む)のMMSEスコアで、ほぼ確実なADであると診断されており、試験結果に影響しそうな他の医学的状態がない。
臨床試験での以前の経験を基に、14日タイトレーション工程を本試験で実行した。
本分析時、以下の数の患者が4期間の各々を完了し、薬物動態学的評価に包含された:
リバスチグミンの薬物動態学的パラメータを表1(カプセル剤処置)および表2(TTS#2処置)に要約する。平均(±SD)血漿濃度−時間プロファイルを図4に示す。
TTS#2の適用中、リバスチグミンプラトー濃度は、全TTSサイズについて8.0時間のメジアンtmaxで達成された。暴露はまた表3に示す通り用量が増えると、カプセル剤よりは少ない程度で、特にAUC24hにおいて過度に増加した。
リバスチグミン(CmaxおよびAUC24h)の暴露パラメータについての変動係数(CV)により評価した患者間変動は、経口投与(39−68%のCV)と比較して、パッチ後の方が一般に低かった(33−48%のCV)。
TTS#2は、標準動物試験および臨床試験において示される通り、カプセル製剤と比較したとき、改善された薬理学的特性を示す。
Claims (2)
- 認知症またはアルツハイマー病の予防、処置または進行遅延のための経皮吸収治療システム(TTS)製剤の製造ための、遊離塩基または薬学的に許容される塩の形のリバスチグミンの使用であって、
リバスチグミンの開始投与量が、9mgリバスチグミンの充填量を有する5cm2の二層TTS製剤のものであり、ここで、その一層が60g/m2の単位面積当たりの重量を有し、かつ以下の組成:
- 遊離塩基または薬学的に許容される塩の形のリバスチグミンを活性成分として含む、認知症またはアルツハイマー病の予防、処置または進行遅延のための組成物であって、該組成物が経皮吸収治療システム(TTS)用であり、
リバスチグミンの開始投与量が、9mgリバスチグミンの充填量を有する5cm2の二層TTS製剤のものであり、ここで、その一層が60g/m2の単位面積当たりの重量を有し、かつ以下の組成:
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US74151105P | 2005-12-01 | 2005-12-01 | |
US60/741,511 | 2005-12-01 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2008543278A Division JP2009517468A (ja) | 2005-12-01 | 2006-10-10 | 経皮吸収治療システム |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2015233544A Division JP6298034B2 (ja) | 2005-12-01 | 2015-11-30 | 経皮吸収治療システム |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2013177419A JP2013177419A (ja) | 2013-09-09 |
JP5938612B2 true JP5938612B2 (ja) | 2016-06-22 |
Family
ID=37716856
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2008543278A Withdrawn JP2009517468A (ja) | 2005-12-01 | 2006-10-10 | 経皮吸収治療システム |
JP2013107198A Active JP5938612B2 (ja) | 2005-12-01 | 2013-05-21 | 経皮吸収治療システム |
JP2015233544A Active JP6298034B2 (ja) | 2005-12-01 | 2015-11-30 | 経皮吸収治療システム |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2008543278A Withdrawn JP2009517468A (ja) | 2005-12-01 | 2006-10-10 | 経皮吸収治療システム |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2015233544A Active JP6298034B2 (ja) | 2005-12-01 | 2015-11-30 | 経皮吸収治療システム |
Country Status (31)
Country | Link |
---|---|
US (3) | US20070128263A1 (ja) |
EP (5) | EP2786748A1 (ja) |
JP (3) | JP2009517468A (ja) |
KR (7) | KR20180050441A (ja) |
CN (2) | CN102048713A (ja) |
AR (2) | AR057152A1 (ja) |
AT (1) | AT11185U1 (ja) |
AU (1) | AU2006320919B2 (ja) |
BR (2) | BR122013013162A2 (ja) |
CA (1) | CA2563110A1 (ja) |
DE (2) | DE14163637T1 (ja) |
DK (5) | DK2292219T3 (ja) |
EC (1) | ECSP088469A (ja) |
ES (1) | ES2414455T3 (ja) |
GT (1) | GT200800075A (ja) |
HK (1) | HK1153646A1 (ja) |
IL (4) | IL191311A (ja) |
MA (1) | MA30022B1 (ja) |
MY (2) | MY151020A (ja) |
NO (1) | NO20082753L (ja) |
NZ (1) | NZ568273A (ja) |
PH (2) | PH12013500771A1 (ja) |
PL (1) | PL2292219T4 (ja) |
PT (1) | PT2292219E (ja) |
RU (1) | RU2450805C2 (ja) |
SG (1) | SG2014014989A (ja) |
SI (1) | SI2292219T1 (ja) |
TN (1) | TNSN08238A1 (ja) |
TW (1) | TWI389709B (ja) |
WO (1) | WO2007064407A1 (ja) |
ZA (1) | ZA200803882B (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2016104737A (ja) * | 2005-12-01 | 2016-06-09 | ノバルティス アーゲー | 経皮吸収治療システム |
Families Citing this family (99)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9248104B2 (en) * | 2006-08-17 | 2016-02-02 | Core Tech Solutions, Inc. | Transdermal methods and systems for treating Alzheimer's disease |
TWI630208B (zh) | 2008-12-08 | 2018-07-21 | 歐陸斯迪公司 | 二氫羥戊甲嗎啡 |
GB0823554D0 (en) | 2008-12-24 | 2009-01-28 | Novartis Ag | Process for the preparation of optically active compounds using transfer hydrogenation |
BRPI1006655A2 (pt) * | 2009-04-17 | 2016-02-10 | 3M Innovative Properties Co | construção de adesivo de gel de silicone e métodos para a produção de uma construção de adesivo de gel de silicone |
WO2010129689A1 (en) * | 2009-05-05 | 2010-11-11 | Forest Laboratories Holdings Limited | Milnacipran formulations |
PL2493457T3 (pl) | 2009-10-30 | 2018-01-31 | Ix Biopharma Ltd | Szybko rozpuszczalna stała postać dawkowana |
WO2011073362A1 (en) | 2009-12-18 | 2011-06-23 | Novartis Ag | Process for the preparation of optically active compounds using pressure hydrogenation |
US10076502B2 (en) | 2009-12-22 | 2018-09-18 | Luye Pharma Ag | Transdermal therapeutic system for administering rivastigmine or derivatives thereof |
WO2011076621A2 (de) * | 2009-12-22 | 2011-06-30 | Acino Ag | Transdermales therapeutisches system zur verabreichung von rivastigmin oder dessen derivaten |
US20100178307A1 (en) * | 2010-01-13 | 2010-07-15 | Jianye Wen | Transdermal anti-dementia active agent formulations and methods for using the same |
DE102010024105A1 (de) * | 2010-06-17 | 2011-12-22 | Grünenthal GmbH | Transdermale Verabreichung von Memantin |
RU2578971C2 (ru) * | 2010-06-17 | 2016-03-27 | Лтс Ломанн Терапи-Системе Аг | Трансдермальное введение мемантина |
DE102010026903A1 (de) | 2010-07-12 | 2012-01-12 | Amw Gmbh | Transdermales therapeutisches System mit Avocadoöl oder Palmöl als Hilfsstoff |
BR112013001550A2 (pt) * | 2010-07-21 | 2016-05-24 | 3M Innovative Properties Co | composições, dispositivos e métodos de adesivos trandérmicos |
EP3578205A1 (en) | 2010-08-06 | 2019-12-11 | ModernaTX, Inc. | A pharmaceutical formulation comprising engineered nucleic acids and medical use thereof |
US20120046383A1 (en) * | 2010-08-19 | 2012-02-23 | Terumo Kabushiki Kaisha | Silicone rubber composition |
WO2012045082A2 (en) | 2010-10-01 | 2012-04-05 | Jason Schrum | Engineered nucleic acids and methods of use thereof |
SI2468274T1 (sl) * | 2010-12-14 | 2015-10-30 | Acino Ag | Transdermalni terapevtski sistem za dajanje aktivne snovi |
KR101788802B1 (ko) * | 2010-12-24 | 2017-10-20 | 주식회사 삼양바이오팜 | 리바스티그민을 함유하는 경피흡수제제 |
KR101054317B1 (ko) * | 2011-01-28 | 2011-08-08 | 신신제약 주식회사 | 리바스티그민을 함유하는 경피흡수제제 |
KR101317158B1 (ko) * | 2011-02-18 | 2013-10-15 | 조선대학교산학협력단 | 갈란타민 또는 그의 염을 함유하는 경피흡수제제 |
AU2012236099A1 (en) | 2011-03-31 | 2013-10-03 | Moderna Therapeutics, Inc. | Delivery and formulation of engineered nucleic acids |
KR20120130073A (ko) * | 2011-05-20 | 2012-11-28 | 에스케이케미칼주식회사 | 리바스티그민 함유 패취 |
JP6017543B2 (ja) * | 2011-05-20 | 2016-11-02 | エスケー ケミカルズ カンパニー, リミテッドSk Chemicals Co., Ltd. | リバスティグミン含有パッチ |
EP2752188B1 (en) | 2011-08-31 | 2020-05-06 | Toyo Ink Sc Holdings Co., Ltd. | Adhesive patch |
US9464124B2 (en) | 2011-09-12 | 2016-10-11 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
EP3682905B1 (en) | 2011-10-03 | 2021-12-01 | ModernaTX, Inc. | Modified nucleosides, nucleotides, and nucleic acids, and uses thereof |
US9301920B2 (en) | 2012-06-18 | 2016-04-05 | Therapeuticsmd, Inc. | Natural combination hormone replacement formulations and therapies |
PT2782584T (pt) | 2011-11-23 | 2021-09-02 | Therapeuticsmd Inc | Preparações e terapias de substituição para hormonoterapias naturais combinadas |
DK2791160T3 (da) | 2011-12-16 | 2022-05-30 | Modernatx Inc | Modificerede mrna-sammensætninger |
KR101399035B1 (ko) * | 2011-12-22 | 2014-05-28 | 주식회사 트랜스덤 | 리바스티그민을 함유하는 경피흡수제제 |
DE102012000369A1 (de) | 2012-01-11 | 2013-07-11 | Alfred E. Tiefenbacher (Gmbh & Co. Kg) | Transdermales therapeutisches System mit Cholinesterase-Hemmer |
US8871245B2 (en) | 2012-02-28 | 2014-10-28 | Nichiban Co., Ltd. | Transdermal patch |
WO2013142339A1 (en) | 2012-03-23 | 2013-09-26 | Novartis Ag | Transdermal therapeutic system and method |
US9283287B2 (en) | 2012-04-02 | 2016-03-15 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of nuclear proteins |
US9572897B2 (en) | 2012-04-02 | 2017-02-21 | Modernatx, Inc. | Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins |
US9878056B2 (en) | 2012-04-02 | 2018-01-30 | Modernatx, Inc. | Modified polynucleotides for the production of cosmetic proteins and peptides |
DE18200782T1 (de) | 2012-04-02 | 2021-10-21 | Modernatx, Inc. | Modifizierte polynukleotide zur herstellung von proteinen im zusammenhang mit erkrankungen beim menschen |
US20150051559A1 (en) * | 2012-04-05 | 2015-02-19 | Sparsha Pharma International Private Limited | Transdermal patch for treatment of dementia or alzheimer type dementia |
CN104114167B (zh) * | 2012-06-12 | 2017-05-17 | Km特兰斯达股份有限公司 | 贴剂 |
US20150196640A1 (en) | 2012-06-18 | 2015-07-16 | Therapeuticsmd, Inc. | Progesterone formulations having a desirable pk profile |
US10806697B2 (en) | 2012-12-21 | 2020-10-20 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US10806740B2 (en) | 2012-06-18 | 2020-10-20 | Therapeuticsmd, Inc. | Natural combination hormone replacement formulations and therapies |
US20130338122A1 (en) | 2012-06-18 | 2013-12-19 | Therapeuticsmd, Inc. | Transdermal hormone replacement therapies |
EP2884969A1 (en) * | 2012-08-15 | 2015-06-24 | Dow Corning Corporation | Multi - layer transdermal drug delivery system |
EP2893927A4 (en) * | 2012-09-03 | 2016-03-09 | Nipro Patch Co Ltd | SKIN PATCH |
KR20140038237A (ko) * | 2012-09-20 | 2014-03-28 | 에스케이케미칼주식회사 | 리바스티그민의 안정성이 개선된 의약품 |
US20140083878A1 (en) * | 2012-09-21 | 2014-03-27 | Mylan Inc. | Transdermal drug delivery device |
WO2014051128A1 (ja) * | 2012-09-28 | 2014-04-03 | 株式会社 ケイ・エム トランスダーム | 貼付剤 |
TW201431570A (zh) | 2012-11-22 | 2014-08-16 | Ucb Pharma Gmbh | 用於經皮投服羅替戈汀(Rotigotine)之多天式貼片 |
HRP20220607T1 (hr) | 2012-11-26 | 2022-06-24 | Modernatx, Inc. | Terminalno modificirana rna |
US10471072B2 (en) | 2012-12-21 | 2019-11-12 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US11246875B2 (en) | 2012-12-21 | 2022-02-15 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US9180091B2 (en) | 2012-12-21 | 2015-11-10 | Therapeuticsmd, Inc. | Soluble estradiol capsule for vaginal insertion |
US11266661B2 (en) | 2012-12-21 | 2022-03-08 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US10568891B2 (en) | 2012-12-21 | 2020-02-25 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US10537581B2 (en) | 2012-12-21 | 2020-01-21 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
WO2014111790A2 (en) | 2013-01-15 | 2014-07-24 | Zydus Technologies Limited | Stable transdermal pharmaceutical drug delivery system comprising rivastigmine |
RU2560668C2 (ru) * | 2013-03-04 | 2015-08-20 | Общество с ограниченной ответственностью Научно-производственное объединение "Клеточные технологии" | Трансдермальный седативный фармацевтический гель для лечения психоэмоциальных расстройств |
US8980864B2 (en) | 2013-03-15 | 2015-03-17 | Moderna Therapeutics, Inc. | Compositions and methods of altering cholesterol levels |
AR095259A1 (es) * | 2013-03-15 | 2015-09-30 | Noven Pharma | Composiciones y métodos para la administración transdérmica de fármacos de amina terciaria |
CN105263488A (zh) * | 2013-03-15 | 2016-01-20 | 纳尔制药有限公司 | 含卡巴拉汀的经皮给药系统 |
GB201309654D0 (en) | 2013-05-30 | 2013-07-17 | Euro Celtique Sa | Method |
SI3040068T1 (sl) | 2013-06-12 | 2021-12-31 | KM Transderm Ltd. | Adhezivna folija za uporabo na koži in perkutani absorpcijski preparat, ki jo uporablja |
TWI745577B (zh) * | 2013-06-12 | 2021-11-11 | 日商Km特蘭斯達股份有限公司 | 經皮吸收製劑 |
US10046151B2 (en) | 2013-07-03 | 2018-08-14 | Lts Lohmann Therapie-Systeme, Ag | Transdermal therapeutic system with electronic component |
EP3052521A1 (en) | 2013-10-03 | 2016-08-10 | Moderna Therapeutics, Inc. | Polynucleotides encoding low density lipoprotein receptor |
RU2018105761A (ru) | 2013-10-07 | 2019-02-26 | ТЕЙКОКУ ФАРМА ЮЭсЭй, ИНК. | Устройства для трансдермальной доставки дексмедетомидина и способы их применения |
RU2648449C2 (ru) | 2013-10-07 | 2018-03-26 | ТЕЙКОКУ ФАРМА ЮЭсЭй, ИНК. | Способы и композиции для трансдермальной доставки неседативного количества дексмедетомидина |
TWI629066B (zh) | 2013-10-07 | 2018-07-11 | 帝國製藥美國股份有限公司 | 使用右美托咪啶經皮組成物用於治療注意力不足過動症、焦慮及失眠的方法及組成物 |
US20160317465A1 (en) | 2013-12-12 | 2016-11-03 | Hisamitsu Pharmaceutical Co., Inc. | Cover material-equipped patch and cover material-equipped patch kit |
CN103877063A (zh) * | 2014-03-24 | 2014-06-25 | 张绪伟 | 一种重酒石酸卡巴拉汀胶囊及其制备方法 |
CN106413695B (zh) | 2014-04-08 | 2019-12-10 | 帝国制药美国公司 | 利伐斯的明透皮组合物及其使用方法 |
WO2015174502A1 (ja) | 2014-05-15 | 2015-11-19 | ニチバン株式会社 | リバスチグミンを含有する貼付剤のための包装体 |
ES2954087T3 (es) | 2014-05-20 | 2023-11-20 | Lts Lohmann Therapie Systeme Ag | Sistema de administración transdérmica que incluye un mediador de interfase |
US11633367B2 (en) | 2014-05-20 | 2023-04-25 | Lts Lohmann Therapie-Systeme Ag | Transdermal delivery system containing rotigotine |
CN106456567A (zh) | 2014-05-20 | 2017-02-22 | Lts勒曼治疗系统股份公司 | 在经皮递送系统中调节活性剂释放的方法 |
JP2017516768A (ja) | 2014-05-22 | 2017-06-22 | セラピューティックスエムディー インコーポレーテッドTherapeuticsmd, Inc. | 天然の併用ホルモン補充療法剤及び療法 |
CN104523656A (zh) * | 2014-11-20 | 2015-04-22 | 美吉斯制药(厦门)有限公司 | 一种卡巴拉汀缓释透皮贴剂及其制备方法 |
DE102015107743A1 (de) | 2015-05-18 | 2016-11-24 | Bsn Medical Gmbh | Silikongelbeschichtete adhäsive Schichtstruktur |
US10328087B2 (en) | 2015-07-23 | 2019-06-25 | Therapeuticsmd, Inc. | Formulations for solubilizing hormones |
US10286077B2 (en) | 2016-04-01 | 2019-05-14 | Therapeuticsmd, Inc. | Steroid hormone compositions in medium chain oils |
KR20180126582A (ko) | 2016-04-01 | 2018-11-27 | 쎄러퓨틱스엠디, 인코퍼레이티드 | 스테로이드 호르몬 약제학적 조성물 |
US9980921B2 (en) * | 2016-06-30 | 2018-05-29 | Taho Pharmaceuticals Ltd. | Transdermal delivery system containing methylphenidate or its salts and methods thereof |
JP6864968B2 (ja) | 2016-08-22 | 2021-04-28 | 救急薬品工業株式会社 | 貼付剤 |
KR102614709B1 (ko) | 2016-12-20 | 2023-12-18 | 에르테에스 로만 테라피-시스테메 아게 | 아세나핀 및 폴리실록산 또는 폴리이소부틸렌을 함유하는 경피흡수 치료 시스템 |
PL3338768T3 (pl) * | 2016-12-20 | 2020-05-18 | Lts Lohmann Therapie-Systeme Ag | Transdermalny system terapeutyczny zawierający asenapinę |
KR102033686B1 (ko) * | 2017-05-19 | 2019-10-18 | 보령제약 주식회사 | 도네페질을 함유하는 마이크로니들 경피 패치 |
EP3678647A1 (en) | 2017-09-05 | 2020-07-15 | LTS Lohmann Therapie-Systeme AG | Transdermal therapeutic system for the transdermal administration of rivastigmine |
US20210000756A1 (en) * | 2018-03-13 | 2021-01-07 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system comprising a silicone acrylic hybrid polymer |
US20210008000A1 (en) * | 2018-03-13 | 2021-01-14 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system comprising a silicone acrylic hybrid polymer |
EP3764998A1 (en) * | 2018-03-13 | 2021-01-20 | LTS Lohmann Therapie-Systeme AG | Transdermal therapeutic system comprising a silicone acrylic hybrid polymer |
CN112533594A (zh) * | 2018-06-19 | 2021-03-19 | 罗曼治疗系统股份公司 | 含有卡巴拉汀的透皮治疗系统 |
CA3101420A1 (en) | 2018-06-20 | 2019-12-26 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system containing asenapine |
US20220133643A1 (en) | 2019-01-31 | 2022-05-05 | Hisamitsu Pharmaceutical Co., Inc. | Adhesive patch |
WO2021005118A1 (en) * | 2019-07-09 | 2021-01-14 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system comprising an active agent-containing layer comprising an acrylic polymer and a skin contact layer comprising a silicone gel adhesive |
CA3146233A1 (en) * | 2019-07-09 | 2021-01-14 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system comprising an active agent-containing layer comprising a silicone-containing polymer and a skin contact layer comprising a silicone gel adhesive |
CN113616625B (zh) * | 2021-08-26 | 2023-05-30 | 大连科翔科技开发有限公司 | 一种卡巴拉汀的长效透皮贴剂 |
WO2024160939A1 (en) * | 2023-02-01 | 2024-08-08 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system for the transdermal administration of huperzine a |
Family Cites Families (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NL195004C (nl) * | 1987-03-04 | 2003-11-04 | Novartis Ag | Fenylcarbamaat bevattend farmaceutisch preparaat. |
US5059426A (en) * | 1989-03-22 | 1991-10-22 | Cygnus Therapeutic Systems | Skin permeation enhancer compositions, and methods and transdermal systems associated therewith |
US5252335A (en) * | 1989-07-12 | 1993-10-12 | Cygnus Therapeutic Systems | Transdermal administration of lisuride |
DE4301783C1 (de) * | 1993-01-23 | 1994-02-03 | Lohmann Therapie Syst Lts | Transdermales therapeutisches System mit Galanthamin als wirksamem Bestandteil |
US6316023B1 (en) | 1998-01-12 | 2001-11-13 | Novartis Ag | TTS containing an antioxidant |
GB9800526D0 (en) * | 1998-01-12 | 1998-03-11 | Ciba Geigy Ag | Organic compounds |
DE19918106A1 (de) * | 1999-04-22 | 2000-10-26 | Lohmann Therapie Syst Lts | Transdermales therapeutisches System mit neutralisierten Acrylathaftklebern |
DE19922662C1 (de) * | 1999-05-18 | 2000-12-28 | Sanol Arznei Schwarz Gmbh | Transdermales therapeutisches System (TTS) Tolterodin enthaltend |
EP1231877A4 (en) * | 1999-11-04 | 2009-03-18 | Xel Herbaceuticals | TRANSDERMALE ADMINISTRATION OF HUPERZIN |
US20030104041A1 (en) * | 1999-12-16 | 2003-06-05 | Tsung-Min Hsu | Transdermal and topical administration of drugs using basic permeation enhancers |
US20020192243A1 (en) * | 1999-12-16 | 2002-12-19 | Tsung-Min Hsu | Transdermal and topical administration of drugs for the treatment of Alzheimer's disease using basic enhancers |
DE10033853A1 (de) * | 2000-07-12 | 2002-01-31 | Hexal Ag | Transdermales therapeutisches System mit hochdispersem Siliziumdioxid |
AU2002235155A1 (en) * | 2000-12-05 | 2002-06-18 | Noven Pharmaceuticals, Inc. | Crystallization inhibition of drugs in transdermal drug delivery systems |
DE10103860B4 (de) | 2001-01-30 | 2004-12-23 | Lts Lohmann Therapie-Systeme Ag | Transdermales therapeutisches System für die Verabreichung carboxylgruppenhaltiger, nichtsteroidaler Antiphlogistika, sowie Verfahren zu seiner Herstellung |
EP1423127A1 (en) * | 2001-08-30 | 2004-06-02 | Ortho-Mcneil Pharmaceutical, Inc. | Treatment of dementia and memory disorders with anticonvulsants and acetylcholinesterase inhibitors |
DE10159745A1 (de) * | 2001-12-05 | 2003-07-03 | Lohmann Therapie Syst Lts | Transdermales Therapeutisches System mit verbessertem Langzeittragekomfort |
SI1509232T1 (sl) * | 2002-05-31 | 2009-04-30 | Lundbeck & Co As H | Kombinacija antagonista nmda in zaviralcev acetilholinesteraze za zdravljenje alzheimerjeve bolezni |
CN100339070C (zh) * | 2002-10-24 | 2007-09-26 | 莫茨药物股份两合公司 | 包含1-氨基环己烷衍生物类和乙酰胆碱酯酶抑制剂类的药物组合物 |
AU2005215134B2 (en) | 2004-02-19 | 2009-01-29 | Novartis Ag | Use of cholinesterase inhibitors for treating vascular depression |
TWI389709B (zh) | 2005-12-01 | 2013-03-21 | Novartis Ag | 經皮治療系統 |
EP2596889B1 (en) * | 2011-11-23 | 2017-04-26 | Sandvik Intellectual Property AB | A cutting insert and a milling tool |
-
2006
- 2006-10-05 TW TW095137245A patent/TWI389709B/zh not_active IP Right Cessation
- 2006-10-10 KR KR1020187012945A patent/KR20180050441A/ko active Search and Examination
- 2006-10-10 KR KR1020137031255A patent/KR20130143729A/ko not_active Application Discontinuation
- 2006-10-10 SG SG2014014989A patent/SG2014014989A/en unknown
- 2006-10-10 EP EP20140163637 patent/EP2786748A1/en not_active Ceased
- 2006-10-10 CN CN2011100034841A patent/CN102048713A/zh active Pending
- 2006-10-10 AR ARP060104447A patent/AR057152A1/es not_active Application Discontinuation
- 2006-10-10 CA CA002563110A patent/CA2563110A1/en active Pending
- 2006-10-10 EP EP10179085.5A patent/EP2292219B9/en not_active Revoked
- 2006-10-10 KR KR1020177006994A patent/KR20170033449A/ko not_active Application Discontinuation
- 2006-10-10 KR KR1020217001087A patent/KR20210008440A/ko not_active Application Discontinuation
- 2006-10-10 US US11/539,979 patent/US20070128263A1/en not_active Abandoned
- 2006-10-10 EP EP17155300.1A patent/EP3235495A1/en not_active Ceased
- 2006-10-10 WO PCT/US2006/039557 patent/WO2007064407A1/en active Application Filing
- 2006-10-10 CN CNA2006800434220A patent/CN101312717A/zh active Pending
- 2006-10-10 BR BRBR122013013162-0A patent/BR122013013162A2/pt not_active Application Discontinuation
- 2006-10-10 BR BRPI0619758-2A patent/BRPI0619758A2/pt not_active Application Discontinuation
- 2006-10-10 DE DE14163637.3T patent/DE14163637T1/de active Pending
- 2006-10-10 PL PL10179085T patent/PL2292219T4/pl unknown
- 2006-10-10 EP EP10179084A patent/EP2286802A1/en not_active Withdrawn
- 2006-10-10 RU RU2008126459/15A patent/RU2450805C2/ru active
- 2006-10-10 KR KR1020227039266A patent/KR20220156666A/ko not_active Application Discontinuation
- 2006-10-10 DK DK10179085.5T patent/DK2292219T3/da active
- 2006-10-10 ES ES10179085T patent/ES2414455T3/es active Active
- 2006-10-10 AU AU2006320919A patent/AU2006320919B2/en active Active
- 2006-10-10 NZ NZ568273A patent/NZ568273A/en unknown
- 2006-10-10 EP EP06816633A patent/EP1959937A1/en not_active Withdrawn
- 2006-10-10 JP JP2008543278A patent/JP2009517468A/ja not_active Withdrawn
- 2006-10-10 MY MYPI20081730 patent/MY151020A/en unknown
- 2006-10-10 PT PT101790855T patent/PT2292219E/pt unknown
- 2006-10-10 SI SI200631618T patent/SI2292219T1/sl unknown
- 2006-10-10 DE DE202006021172U patent/DE202006021172U1/de not_active Ceased
- 2006-10-10 KR KR1020147010333A patent/KR20140072108A/ko not_active Application Discontinuation
- 2006-10-10 KR KR1020087013112A patent/KR20080071581A/ko not_active Application Discontinuation
-
2008
- 2008-05-07 IL IL191311A patent/IL191311A/en active IP Right Grant
- 2008-05-07 ZA ZA200803882A patent/ZA200803882B/xx unknown
- 2008-05-20 MY MYPI2013003893A patent/MY162986A/en unknown
- 2008-05-26 EC EC2008008469A patent/ECSP088469A/es unknown
- 2008-05-28 GT GT200800075A patent/GT200800075A/es unknown
- 2008-05-30 TN TNP2008000238A patent/TNSN08238A1/en unknown
- 2008-06-02 MA MA30991A patent/MA30022B1/fr unknown
- 2008-06-18 NO NO20082753A patent/NO20082753L/no unknown
- 2008-10-16 AT AT0059308U patent/AT11185U1/de not_active IP Right Cessation
- 2008-12-19 HK HK11107634.4A patent/HK1153646A1/xx unknown
-
2013
- 2013-01-31 DK DKBA201300014U patent/DK201300014U3/da not_active IP Right Cessation
- 2013-01-31 DK DK201300015U patent/DK201300015Y4/da not_active IP Right Cessation
- 2013-04-12 DK DKBA201300059U patent/DK201300059U3/da not_active IP Right Cessation
- 2013-04-19 PH PH12013500771A patent/PH12013500771A1/en unknown
- 2013-04-19 PH PH12013500772A patent/PH12013500772B1/en unknown
- 2013-05-21 JP JP2013107198A patent/JP5938612B2/ja active Active
- 2013-05-31 US US13/906,922 patent/US20130266633A1/en not_active Abandoned
-
2014
- 2014-01-21 US US14/159,609 patent/US20140134230A1/en not_active Abandoned
- 2014-07-24 AR ARP140102752A patent/AR097045A2/es not_active Application Discontinuation
- 2014-08-25 IL IL234291A patent/IL234291A/en active IP Right Grant
- 2014-08-28 IL IL234364A patent/IL234364A/en active IP Right Grant
-
2015
- 2015-11-30 JP JP2015233544A patent/JP6298034B2/ja active Active
-
2016
- 2016-10-07 DK DKBA201600113U patent/DK201600113Y4/da not_active IP Right Cessation
-
2017
- 2017-02-23 IL IL250734A patent/IL250734A0/en unknown
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2016104737A (ja) * | 2005-12-01 | 2016-06-09 | ノバルティス アーゲー | 経皮吸収治療システム |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5938612B2 (ja) | 経皮吸収治療システム | |
US10729686B2 (en) | Pharmaceutical compositions | |
US20080044461A1 (en) | Transdermal methods and systems for treating Alzheimer's disease | |
Gupta et al. | Transdermal delivery: product and patent update | |
MX2008006956A (es) | Sistema terapeutico transdermico | |
JP6978417B2 (ja) | プラミペキソール経皮送達系及びその使用 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130521 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20130521 |
|
RD03 | Notification of appointment of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7423 Effective date: 20140612 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20140624 |
|
RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20140613 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140728 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20140924 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20140929 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20141224 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20150728 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20151130 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20160112 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20160203 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20160308 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20160406 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5938612 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |