JPH10501816A - 経粘膜輸送システム - Google Patents
経粘膜輸送システムInfo
- Publication number
- JPH10501816A JPH10501816A JP8502353A JP50235396A JPH10501816A JP H10501816 A JPH10501816 A JP H10501816A JP 8502353 A JP8502353 A JP 8502353A JP 50235396 A JP50235396 A JP 50235396A JP H10501816 A JPH10501816 A JP H10501816A
- Authority
- JP
- Japan
- Prior art keywords
- heparin
- matrix
- formulation
- anticoagulant
- weight
- 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.)
- Ceased
Links
- 239000000203 mixture Substances 0.000 claims abstract description 139
- 238000009472 formulation Methods 0.000 claims abstract description 96
- 239000011159 matrix material Substances 0.000 claims abstract description 73
- 239000003146 anticoagulant agent Substances 0.000 claims abstract description 61
- 229940127219 anticoagulant drug Drugs 0.000 claims abstract description 61
- 239000000853 adhesive Substances 0.000 claims abstract description 8
- 230000001070 adhesive effect Effects 0.000 claims abstract description 8
- 230000036765 blood level Effects 0.000 claims abstract description 8
- 229920000669 heparin Polymers 0.000 claims description 48
- 238000000034 method Methods 0.000 claims description 41
- 230000003232 mucoadhesive effect Effects 0.000 claims description 39
- 238000002360 preparation method Methods 0.000 claims description 36
- 239000011347 resin Substances 0.000 claims description 32
- 229920005989 resin Polymers 0.000 claims description 31
- 239000000843 powder Substances 0.000 claims description 26
- 239000003055 low molecular weight heparin Substances 0.000 claims description 20
- 229940127215 low-molecular weight heparin Drugs 0.000 claims description 20
- -1 Polyoxyethylene Polymers 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- 229920002884 Laureth 4 Polymers 0.000 claims description 10
- 229940062711 laureth-9 Drugs 0.000 claims description 10
- ONJQDTZCDSESIW-UHFFFAOYSA-N polidocanol Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO ONJQDTZCDSESIW-UHFFFAOYSA-N 0.000 claims description 10
- 239000002952 polymeric resin Substances 0.000 claims description 10
- 229920003002 synthetic resin Polymers 0.000 claims description 9
- 239000003961 penetration enhancing agent Substances 0.000 claims description 8
- 241000124008 Mammalia Species 0.000 claims description 7
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 7
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical group [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 7
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 7
- 230000004888 barrier function Effects 0.000 claims description 6
- 230000002209 hydrophobic effect Effects 0.000 claims description 6
- 229920001971 elastomer Polymers 0.000 claims description 5
- 239000008176 lyophilized powder Substances 0.000 claims description 5
- HBXWUCXDUUJDRB-UHFFFAOYSA-N 1-octadecoxyoctadecane Chemical compound CCCCCCCCCCCCCCCCCCOCCCCCCCCCCCCCCCCCC HBXWUCXDUUJDRB-UHFFFAOYSA-N 0.000 claims description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 4
- 229940018872 dalteparin sodium Drugs 0.000 claims description 4
- 229960005153 enoxaparin sodium Drugs 0.000 claims description 4
- 229950003543 nadroparin calcium Drugs 0.000 claims description 4
- 229910052708 sodium Inorganic materials 0.000 claims description 4
- 239000011734 sodium Substances 0.000 claims description 4
- CIJQTPFWFXOSEO-NDMITSJXSA-J tetrasodium;(2r,3r,4s)-2-[(2r,3s,4r,5r,6s)-5-acetamido-6-[(1r,2r,3r,4r)-4-[(2r,3s,4r,5r,6r)-5-acetamido-6-[(4r,5r,6r)-2-carboxylato-4,5-dihydroxy-6-[[(1r,3r,4r,5r)-3-hydroxy-4-(sulfonatoamino)-6,8-dioxabicyclo[3.2.1]octan-2-yl]oxy]oxan-3-yl]oxy-2-(hydroxy Chemical compound [Na+].[Na+].[Na+].[Na+].O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1O)NC(C)=O)O[C@@H]1C(C[C@H]([C@@H]([C@H]1O)O)O[C@@H]1[C@@H](CO)O[C@H](OC2C(O[C@@H](OC3[C@@H]([C@@H](NS([O-])(=O)=O)[C@@H]4OC[C@H]3O4)O)[C@H](O)[C@H]2O)C([O-])=O)[C@H](NC(C)=O)[C@H]1C)C([O-])=O)[C@@H]1OC(C([O-])=O)=C[C@H](O)[C@H]1O CIJQTPFWFXOSEO-NDMITSJXSA-J 0.000 claims description 4
- 229940064689 tinzaparin sodium Drugs 0.000 claims description 4
- ZSLUVFAKFWKJRC-IGMARMGPSA-N 232Th Chemical compound [232Th] ZSLUVFAKFWKJRC-IGMARMGPSA-N 0.000 claims description 3
- GAMKNLFIHBMGQT-UHFFFAOYSA-N 3-hexadecanoyloxy-4-(trimethylazaniumyl)butanoate;hydrochloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC(=O)OC(CC(O)=O)C[N+](C)(C)C GAMKNLFIHBMGQT-UHFFFAOYSA-N 0.000 claims description 3
- 229910052776 Thorium Inorganic materials 0.000 claims description 3
- 239000000806 elastomer Substances 0.000 claims description 3
- 239000002245 particle Substances 0.000 claims description 3
- 210000005178 buccal mucosa Anatomy 0.000 claims description 2
- 150000002170 ethers Chemical class 0.000 claims description 2
- 125000000400 lauroyl group Chemical group O=C([*])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 claims description 2
- 230000002093 peripheral effect Effects 0.000 claims description 2
- IWQPOPSAISBUAH-VOVMJQHHSA-M sodium;2-[[(2z)-2-[(3r,4s,5s,8s,9s,10s,11r,13r,14s,16s)-16-acetyl-3,11-dihydroxy-4,8,10,14-tetramethyl-2,3,4,5,6,7,9,11,12,13,15,16-dodecahydro-1h-cyclopenta[a]phenanthren-17-ylidene]-6-methylheptanoyl]amino]ethanesulfonate Chemical compound [Na+].C1C[C@@H](O)[C@@H](C)[C@@H]2CC[C@]3(C)[C@@]4(C)C[C@H](C(C)=O)/C(=C(C(=O)NCCS([O-])(=O)=O)/CCCC(C)C)[C@@H]4C[C@@H](O)[C@H]3[C@]21C IWQPOPSAISBUAH-VOVMJQHHSA-M 0.000 claims description 2
- 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 claims 1
- 210000004877 mucosa Anatomy 0.000 abstract description 4
- 239000000499 gel Substances 0.000 description 70
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 39
- 229960002897 heparin Drugs 0.000 description 38
- 238000001727 in vivo Methods 0.000 description 15
- 241000700159 Rattus Species 0.000 description 14
- 230000001858 anti-Xa Effects 0.000 description 14
- 210000004027 cell Anatomy 0.000 description 14
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 229940079593 drug Drugs 0.000 description 10
- 239000003814 drug Substances 0.000 description 10
- 238000011552 rat model Methods 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 230000035515 penetration Effects 0.000 description 9
- 230000000694 effects Effects 0.000 description 8
- 229920001195 polyisoprene Polymers 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 241000282472 Canis lupus familiaris Species 0.000 description 7
- 229920002125 Sokalan® Polymers 0.000 description 7
- 239000003623 enhancer Substances 0.000 description 7
- 210000004347 intestinal mucosa Anatomy 0.000 description 7
- 229920002367 Polyisobutene Polymers 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000011833 dog model Methods 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 230000019635 sulfation Effects 0.000 description 6
- 238000005670 sulfation reaction Methods 0.000 description 6
- 238000010998 test method Methods 0.000 description 6
- 230000015556 catabolic process Effects 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 238000006731 degradation reaction Methods 0.000 description 5
- 239000000017 hydrogel Substances 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 150000002016 disaccharides Chemical group 0.000 description 4
- 238000012377 drug delivery Methods 0.000 description 4
- 238000007429 general method Methods 0.000 description 4
- 239000008240 homogeneous mixture Substances 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 229910052698 phosphorus Inorganic materials 0.000 description 4
- 239000011574 phosphorus Substances 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 238000000807 solvent casting Methods 0.000 description 4
- 238000003892 spreading Methods 0.000 description 4
- 230000007480 spreading Effects 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 3
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 229920002301 cellulose acetate Polymers 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 229920001577 copolymer Polymers 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 238000004108 freeze drying Methods 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- 239000004570 mortar (masonry) Substances 0.000 description 3
- 210000002200 mouth mucosa Anatomy 0.000 description 3
- 210000004400 mucous membrane Anatomy 0.000 description 3
- 229920001542 oligosaccharide Polymers 0.000 description 3
- 150000002482 oligosaccharides Chemical class 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 210000003370 receptor cell Anatomy 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- FDCJDKXCCYFOCV-UHFFFAOYSA-N 1-hexadecoxyhexadecane Chemical compound CCCCCCCCCCCCCCCCOCCCCCCCCCCCCCCCC FDCJDKXCCYFOCV-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 2
- 239000004925 Acrylic resin Substances 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 206010014522 Embolism venous Diseases 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 229920002683 Glycosaminoglycan Polymers 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- RRHGJUQNOFWUDK-UHFFFAOYSA-N Isoprene Chemical compound CC(=C)C=C RRHGJUQNOFWUDK-UHFFFAOYSA-N 0.000 description 2
- 229920004942 NATSYN® 2210 Polymers 0.000 description 2
- 241000282887 Suidae Species 0.000 description 2
- YTKLYANZDLHMLG-KVTDHHQDSA-N [(2r,3s,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]methyl hydrogen sulfate Chemical group OC[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](O)[C@@H]1O YTKLYANZDLHMLG-KVTDHHQDSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000002429 anti-coagulating effect Effects 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 2
- 229960003964 deoxycholic acid Drugs 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000009792 diffusion process Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 150000004676 glycans Polymers 0.000 description 2
- 239000002634 heparin fragment Substances 0.000 description 2
- 230000036571 hydration Effects 0.000 description 2
- 238000006703 hydration reaction Methods 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
- 239000004584 polyacrylic acid Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 239000005060 rubber Substances 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- FHHPUSMSKHSNKW-SMOYURAASA-M sodium deoxycholate Chemical compound [Na+].C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 FHHPUSMSKHSNKW-SMOYURAASA-M 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 208000004043 venous thromboembolism Diseases 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 1
- IFPMZBBHBZQTOV-UHFFFAOYSA-N 1,3,5-trinitro-2-(2,4,6-trinitrophenyl)-4-[2,4,6-trinitro-3-(2,4,6-trinitrophenyl)phenyl]benzene Chemical compound [O-][N+](=O)C1=CC([N+](=O)[O-])=CC([N+]([O-])=O)=C1C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C(C=2C(=C(C=3C(=CC(=CC=3[N+]([O-])=O)[N+]([O-])=O)[N+]([O-])=O)C(=CC=2[N+]([O-])=O)[N+]([O-])=O)[N+]([O-])=O)=C1[N+]([O-])=O IFPMZBBHBZQTOV-UHFFFAOYSA-N 0.000 description 1
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- JAHNSTQSQJOJLO-UHFFFAOYSA-N 2-(3-fluorophenyl)-1h-imidazole Chemical compound FC1=CC=CC(C=2NC=CN=2)=C1 JAHNSTQSQJOJLO-UHFFFAOYSA-N 0.000 description 1
- JKNCOURZONDCGV-UHFFFAOYSA-N 2-(dimethylamino)ethyl 2-methylprop-2-enoate Chemical compound CN(C)CCOC(=O)C(C)=C JKNCOURZONDCGV-UHFFFAOYSA-N 0.000 description 1
- NLMKTBGFQGKQEV-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-hexadecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO NLMKTBGFQGKQEV-UHFFFAOYSA-N 0.000 description 1
- JKXYOQDLERSFPT-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-octadecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO JKXYOQDLERSFPT-UHFFFAOYSA-N 0.000 description 1
- 229920000178 Acrylic resin Polymers 0.000 description 1
- 229910002012 Aerosil® Inorganic materials 0.000 description 1
- 229910002016 Aerosil® 200 Inorganic materials 0.000 description 1
- 102000004411 Antithrombin III Human genes 0.000 description 1
- 108090000935 Antithrombin III Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 206010053567 Coagulopathies Diseases 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 1
- 244000039154 Erica Species 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- LFVLUOAHQIVABZ-UHFFFAOYSA-N Iodofenphos Chemical compound COP(=S)(OC)OC1=CC(Cl)=C(I)C=C1Cl LFVLUOAHQIVABZ-UHFFFAOYSA-N 0.000 description 1
- VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical group CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
- 229920004940 NATSYN® Polymers 0.000 description 1
- 241000209094 Oryza Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 229920005372 Plexiglas® Polymers 0.000 description 1
- 208000000474 Poliomyelitis Diseases 0.000 description 1
- 239000005062 Polybutadiene Substances 0.000 description 1
- 229920000148 Polycarbophil calcium Polymers 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000004820 Pressure-sensitive adhesive Substances 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 229920002807 Thiomer Polymers 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 208000001435 Thromboembolism Diseases 0.000 description 1
- DQTRACMFIGDHSN-IVMDWMLBSA-N [(3r,4r,5s,6r)-2,4,5-trihydroxy-6-(sulfooxymethyl)oxan-3-yl]sulfamic acid Chemical group OC1O[C@H](COS(O)(=O)=O)[C@@H](O)[C@H](O)[C@H]1NS(O)(=O)=O DQTRACMFIGDHSN-IVMDWMLBSA-N 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 230000004523 agglutinating effect Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 239000003945 anionic surfactant Substances 0.000 description 1
- 229960005348 antithrombin iii Drugs 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-QZABAPFNSA-N beta-D-glucosamine Chemical compound N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-QZABAPFNSA-N 0.000 description 1
- 239000003613 bile acid Substances 0.000 description 1
- 239000000227 bioadhesive Substances 0.000 description 1
- 230000001851 biosynthetic effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- FACXGONDLDSNOE-UHFFFAOYSA-N buta-1,3-diene;styrene Chemical compound C=CC=C.C=CC1=CC=CC=C1.C=CC1=CC=CC=C1 FACXGONDLDSNOE-UHFFFAOYSA-N 0.000 description 1
- 229920005549 butyl rubber Polymers 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 150000001734 carboxylic acid salts Chemical class 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- HNEGQIOMVPPMNR-IHWYPQMZSA-N citraconic acid Chemical compound OC(=O)C(/C)=C\C(O)=O HNEGQIOMVPPMNR-IHWYPQMZSA-N 0.000 description 1
- 229940018557 citraconic acid Drugs 0.000 description 1
- 230000035602 clotting Effects 0.000 description 1
- 239000000701 coagulant Substances 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 239000004020 conductor Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 239000001064 degrader Substances 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- GUJOJGAPFQRJSV-UHFFFAOYSA-N dialuminum;dioxosilane;oxygen(2-);hydrate Chemical compound O.[O-2].[O-2].[O-2].[Al+3].[Al+3].O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O GUJOJGAPFQRJSV-UHFFFAOYSA-N 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 229940043264 dodecyl sulfate Drugs 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 210000004195 gingiva Anatomy 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229950006191 gluconic acid Drugs 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- ZFGMDIBRIDKWMY-PASTXAENSA-N heparin Chemical compound CC(O)=N[C@@H]1[C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O[C@@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O[C@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@@H](O[C@@H]3[C@@H](OC(O)[C@H](OS(O)(=O)=O)[C@H]3O)C(O)=O)O[C@@H]2O)CS(O)(=O)=O)[C@H](O)[C@H]1O ZFGMDIBRIDKWMY-PASTXAENSA-N 0.000 description 1
- 239000002565 heparin fraction Substances 0.000 description 1
- 229960001008 heparin sodium Drugs 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 229920003049 isoprene rubber Polymers 0.000 description 1
- AEMOLEFTQBMNLQ-CLQWQSTFSA-N l-iduronic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@H](O)[C@@H](O)[C@@H]1O AEMOLEFTQBMNLQ-CLQWQSTFSA-N 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- SXNRYTMXFYZYMT-UHFFFAOYSA-L lithium sodium dodecyl sulfate Chemical compound [Li+].[Na+].CCCCCCCCCCCCOS([O-])(=O)=O.CCCCCCCCCCCCOS([O-])(=O)=O SXNRYTMXFYZYMT-UHFFFAOYSA-L 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- LVHBHZANLOWSRM-UHFFFAOYSA-N methylenebutanedioic acid Natural products OC(=O)CC(=C)C(O)=O LVHBHZANLOWSRM-UHFFFAOYSA-N 0.000 description 1
- 238000003801 milling Methods 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000014508 negative regulation of coagulation Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- WXZMFSXDPGVJKK-UHFFFAOYSA-N pentaerythritol Chemical compound OCC(CO)(CO)CO WXZMFSXDPGVJKK-UHFFFAOYSA-N 0.000 description 1
- JOHZPMXAZQZXHR-UHFFFAOYSA-N pipemidic acid Chemical compound N1=C2N(CC)C=C(C(O)=O)C(=O)C2=CN=C1N1CCNCC1 JOHZPMXAZQZXHR-UHFFFAOYSA-N 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920002857 polybutadiene Polymers 0.000 description 1
- 229950005134 polycarbophil Drugs 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Polymers 0.000 description 1
- 229920006264 polyurethane film Polymers 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000004080 punching Methods 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 229940000204 reviparin sodium Drugs 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 229940100486 rice starch Drugs 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 229910052814 silicon oxide Inorganic materials 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 229940045946 sodium taurodeoxycholate Drugs 0.000 description 1
- YXHRQQJFKOHLAP-FVCKGWAHSA-M sodium;2-[[(4r)-4-[(3r,5r,8r,9s,10s,12s,13r,14s,17r)-3,12-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]ethanesulfonate Chemical compound [Na+].C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 YXHRQQJFKOHLAP-FVCKGWAHSA-M 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 229920000468 styrene butadiene styrene block copolymer Polymers 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 238000010345 tape casting Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 229950003937 tolonium Drugs 0.000 description 1
- HNONEKILPDHFOL-UHFFFAOYSA-M tolonium chloride Chemical compound [Cl-].C1=C(C)C(N)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 HNONEKILPDHFOL-UHFFFAOYSA-M 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
Classifications
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
- A61K31/727—Heparin; Heparan
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Physiology (AREA)
- Nutrition Science (AREA)
- Molecular Biology (AREA)
- Hematology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Steroid Compounds (AREA)
Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.治療に有効な量のヘパリン様抗凝血物質を含むマトリックスと、粘膜表面 への該ヘパリン様抗凝血物質の放出を許容するのに十分な時間、該粘膜表面に前 記マトリックスを接触させ続けるための手段と、を含む薬剤輸送製剤。 2.前記粘膜表面にマトリックスを接触させ続けるための手段が粘膜接着剤で あることを特徴とする請求項1に記載の製剤。 3.前記ヘパリン様抗凝血物質が低分子量ヘパリンであることを特徴とする請 求項1に記載の製剤。 4.前記ヘパリン様抗凝血物質が約1000〜約7500ダルトンの間の平均分子量を 有することを特徴とする請求項1に記載の製剤。 5.前記ヘパリン様抗凝血物質が約3500〜約5500ダルトンの間の平均分子量を 有することを特徴とする請求項1に記載の製剤。 6.前記ヘパリン様抗凝血物質が、ダルテパリンナトリウム、エノキサパリン ナトリウム、ナドロパリンカルシウム、パルナパリンナトリウム、レビパリンナ トリウム及びチンザパリンナトリウムからなる群から選択されることを特徴とす る請求項1に記載の製剤。 7.前記ヘパリン様抗凝血物質が前記マトリックスの全重量を基にして約1〜 約95重量%の量で該マトリックス中に存在することを特徴とする請求項1に記載 の製剤。 8.前記マトリックスがゲルの形態であることを特徴とする請求項11に記載の 製剤。 9.前記マトリックスが錠剤の形態であることを特徴とする請求項1に記載の 製剤。 10.前記マトリックスが粉体の形態であることを特徴とする請求項1に記載の 製剤。 11.前記マトリックスが凍結乾燥された粉体の形態であることを特徴とする請 求項1に記載の製剤。 12.前記マトリックスが浸透エンハンサーを更に含むこと特徴とする請求項1 に記載の製剤。 13.前記浸透エンハンサーが、ドデシル硫酸ナトリウム、Laureth 9、デオキ シコール酸ナトリウム、タウロ−24,25−ジヒドロフシジン酸ナトリウム、パル ミトイルDLカルニチンクロライド、ドデカノイルL−α−ホスファチジルコリン 、ポリオキシエチレン20ステアリルエーテル、及びポリオキシエチレン20セチル エーテルからなる群から選択されることを特徴とする請求項12に記載の製剤。 14.前記浸透エンハンサーが前記マトリックスの全重量を基にして約2重量% 〜約10重量%の量で該マトリックス中に存在することを特徴とする請求項12に記 載の方法。 15.前記粘膜接着剤が、 i)約100μmの以下の平均粒子径を有し、ポリマー樹脂の全重量を基にして 少くとも約55重量%のカルボン酸成分を含む該粒状ポリマー樹脂と、 ii)該樹脂の100重量部を基にして約20重量部〜約250重量部の疎水性エラスト マー構成物であって、前記樹脂が該エラストマー構成物に実質的に全体に分散さ れているエラストマー構成物と、 を含み、前記粘膜接着剤が前記樹脂の全重量を基にして約10重量%未満の水を含 むことを特徴とする請求項2に記載の製剤。 16.i)裏材層と、 ii)該裏材層の一表面に隣接し、治療に有効な量のヘパリン様抗凝血物質を含 むマトリックスであって、該マトリックスが前記裏材層より小さい周縁部を有し 、前記裏材層の一部分が前記マトリックスの周縁部が外側に広がるマトリックス と、 iii)前記裏材層の前記外側に広がる部分の少くとも一部を覆う粘膜接着剤層 と、 を含むことを特徴とする請求項2に記載の製剤。 17.哺乳動物において、ヘパリン様抗凝血物質の治療に有効な血液レベルを達 成及び/又は維持する方法であって、 i)請求項1に記載の製剤を供するステップと、 ii)該製剤を前記哺乳動物の粘膜表面に接触させるステップと、 iii)前記ヘパリン様抗凝血物質の治療に有効な血液レベルを確立及び/又は 維持するのに十分な時間、前記製剤を前記粘膜表面に接触させ続けるステップと 、 を含むことを特徴とする方法。 18.前記粘膜表面が口部の粘膜表面であることを特徴とする請求項17に記載の 方法。 19.前記粘膜表面が頬部の粘膜であることを特徴とする請求項17に記載の方法 。 20.i)裏材層と、 ii)該裏材層の一表面に隣接し、治療に有効な量のヘパリン様抗凝血物質を含 むマトリックスと、 iii)該マトリックス周縁部のまわりの粘膜接着剤と、 iv)前記マトリックスと前記粘膜接着剤との間に介在するバリアー要素と、 を含むことを特徴とする請求項2に記載の製剤。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/259,873 | 1994-06-15 | ||
US08/259,873 US5639469A (en) | 1994-06-15 | 1994-06-15 | Transmucosal delivery system |
PCT/US1995/007358 WO1995034286A1 (en) | 1994-06-15 | 1995-06-09 | Transmucosal delivery system |
Publications (1)
Publication Number | Publication Date |
---|---|
JPH10501816A true JPH10501816A (ja) | 1998-02-17 |
Family
ID=22986785
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP8502353A Ceased JPH10501816A (ja) | 1994-06-15 | 1995-06-09 | 経粘膜輸送システム |
Country Status (7)
Country | Link |
---|---|
US (2) | US5639469A (ja) |
EP (1) | EP0804154A1 (ja) |
JP (1) | JPH10501816A (ja) |
AU (1) | AU694695B2 (ja) |
CA (1) | CA2190778C (ja) |
NZ (1) | NZ288104A (ja) |
WO (1) | WO1995034286A1 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPWO2019004088A1 (ja) * | 2017-06-27 | 2020-04-23 | 株式会社バイオセレンタック | 粘膜付着性経口製剤 |
Families Citing this family (53)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5888984A (en) * | 1994-05-12 | 1999-03-30 | Dermal Research Laboratories, Inc. | Pharmaceutical composition of complex carbohydrates and essential oils and methods of using the same |
US5639469A (en) * | 1994-06-15 | 1997-06-17 | Minnesota Mining And Manufacturing Company | Transmucosal delivery system |
US6992107B1 (en) * | 1995-03-10 | 2006-01-31 | Photocure Asa | Esters of 5-aminolevulinic acid and their use as photosensitizing compounds in photochemotherapy |
CN1072482C (zh) * | 1996-11-08 | 2001-10-10 | 山东医科大学 | 低分子肝素脂质体喷胶剂及制备工艺 |
AP1390A (en) * | 1996-11-27 | 2005-04-15 | Aventis Pharmaceuticals Products Inc | Pharmaceutical composition comprising a compound having anti-Xa activity and a platelet aggregation antagonist compound. |
FR2762513B1 (fr) * | 1997-04-23 | 2003-08-22 | Permatec Pharma Ag | Comprimes bioadhesifs |
US7001609B1 (en) * | 1998-10-02 | 2006-02-21 | Regents Of The University Of Minnesota | Mucosal originated drug delivery systems and animal applications |
GB9826192D0 (en) * | 1998-12-01 | 1999-01-20 | Controlled Theraputics Scotlan | Oral transmucosal delivery |
AU2745700A (en) * | 1999-02-01 | 2000-08-18 | Dermal Research Laboratories, Inc. | A pharmaceutical composition of complex carbohydrates and essential oils and methods of using the same |
US8119159B2 (en) * | 1999-02-22 | 2012-02-21 | Merrion Research Iii Limited | Solid oral dosage form containing an enhancer |
US20070148228A1 (en) * | 1999-02-22 | 2007-06-28 | Merrion Research I Limited | Solid oral dosage form containing an enhancer |
US7658938B2 (en) * | 1999-02-22 | 2010-02-09 | Merrion Reasearch III Limited | Solid oral dosage form containing an enhancer |
KR20020032444A (ko) * | 1999-06-30 | 2002-05-03 | 잭 허쉬 | 응괴 연관된 응고 인자를 억제하는 헤파린 조성물 |
WO2001037802A1 (en) * | 1999-11-29 | 2001-05-31 | Advanced Research And Technology Institute, Inc. | Sustained percutaneous delivery of a biologically active substance |
US20020110585A1 (en) | 1999-11-30 | 2002-08-15 | Godbey Kristin J. | Patch therapeutic agent delivery device having texturized backing |
TWI227143B (en) | 1999-12-15 | 2005-02-01 | Guo-Jiun Sung | In situ gel formation for ophthalmic delivery by combining Pluronic/Carbopol medic composition and its preparing method |
GB0018527D0 (en) * | 2000-07-27 | 2000-09-13 | Photocure Asa | Composition |
US7879824B2 (en) | 2001-07-31 | 2011-02-01 | Dermal Research Laboratories, Inc. | Methods of preventing or treating diseases and conditions using complex carbohydrates |
MXPA03001986A (es) * | 2000-09-08 | 2004-03-19 | Hamilton Civic Hospitals Res | Composiciones antitromboticas. |
US7803392B2 (en) * | 2000-12-27 | 2010-09-28 | University Of Kentucky Research Foundation | pH-Sensitive mucoadhesive film-forming gels and wax-film composites suitable for topical and mucosal delivery of molecules |
US6730330B2 (en) | 2001-02-14 | 2004-05-04 | Gw Pharma Limited | Pharmaceutical formulations |
US10004684B2 (en) | 2001-02-14 | 2018-06-26 | Gw Pharma Limited | Pharmaceutical formulations |
GB2380129B (en) * | 2001-02-14 | 2004-08-11 | Gw Pharma Ltd | Pharmaceutical formulations |
DE10107659B4 (de) * | 2001-02-19 | 2008-03-13 | Lts Lohmann Therapie-Systeme Ag | Mucoadhäsive zerfallsfähige Arzneizubereitung zur Wirkstoffverabreichung in der Veterinär- und Humanmedizin |
AU2002319653A1 (en) * | 2001-07-20 | 2003-03-03 | Samir Mitragotri | Method for oral drug delivery |
US6585997B2 (en) | 2001-08-16 | 2003-07-01 | Access Pharmaceuticals, Inc. | Mucoadhesive erodible drug delivery device for controlled administration of pharmaceuticals and other active compounds |
US20060073174A1 (en) * | 2001-08-16 | 2006-04-06 | Access Pharmaceuticals, Inc. | Adherent and erodible film to treat a moist surface of a body tissue |
US9308220B2 (en) * | 2001-12-11 | 2016-04-12 | Cosmo Technologies Limited | Pharmaceutical compositions for the oral administration of heparin or derivatives thereof |
US20050181032A1 (en) * | 2002-06-25 | 2005-08-18 | Acrux Dds Pty Ltd. | Metastable pharmaceutical compositions |
US8999372B2 (en) * | 2002-11-14 | 2015-04-07 | Cure Pharmaceutical Corporation | Methods for modulating dissolution, bioavailability, bioequivalence and drug delivery profile of thin film drug delivery systems, controlled-release thin film dosage formats, and methods for their manufacture and use |
US20040131662A1 (en) | 2003-11-12 | 2004-07-08 | Davidson Robert S. | Method and apparatus for minimizing heat, moisture, and shear damage to medicants and other compositions during incorporation of same with edible films |
US20040191302A1 (en) | 2003-03-28 | 2004-09-30 | Davidson Robert S. | Method and apparatus for minimizing heat, moisture, and shear damage to medicants and other compositions during incorporation of same with edible films |
US9561182B2 (en) * | 2003-08-22 | 2017-02-07 | Cure Pharmaceutical Corporation | Edible films for administration of medicaments to animals, methods for their manufacture and methods for their use for the treatment of animals |
US7306812B2 (en) | 2003-05-09 | 2007-12-11 | Cephalon, Inc. | Dissolvable backing layer for use with a transmucosal delivery device |
US7276246B2 (en) * | 2003-05-09 | 2007-10-02 | Cephalon, Inc. | Dissolvable backing layer for use with a transmucosal delivery device |
US20060252010A1 (en) * | 2005-05-09 | 2006-11-09 | Sunnen Gerard V | Sodium chloride pad for treatment of dental conditions |
US20080248090A1 (en) * | 2005-05-09 | 2008-10-09 | Sunnen Gerard V | Graduated concentration sodium chloride patches for the treatment of dental conditions |
WO2007102817A1 (en) * | 2006-03-07 | 2007-09-13 | Innozen, Inc. | Methods for modulating dissolution, bioavailability, bioequivalence and drug delivery profile of thin film drug delivery systems, controlled-release thin film dosage formats, and methods for their manufacture and use |
US7704977B2 (en) * | 2006-04-07 | 2010-04-27 | Merrion Research Iii Limited | Solid oral dosage form containing an enhancer |
CA2650040A1 (en) * | 2006-05-02 | 2007-11-08 | Panacea Biotec Ltd | Transmucosal composition |
CA2654566A1 (en) * | 2006-06-09 | 2007-12-21 | Merrion Research Iii Limited | Solid oral dosage form containing an enhancer |
US20080112974A1 (en) * | 2006-09-08 | 2008-05-15 | Duotol Ab | Method for inducing mucosal humoral and cell-mediated immune responses by sublingual administration of antigens |
US8802156B2 (en) | 2007-11-14 | 2014-08-12 | Laboratorios Farmacéuticos Rovi, S.A. | Pharmaceutical forms for the release of active compounds |
JP2011519928A (ja) * | 2008-05-07 | 2011-07-14 | メリオン・リサーチ・Iii・リミテッド | ペプチドの組成物及びその調製方法 |
CA2751854A1 (en) * | 2009-02-25 | 2010-09-02 | Merrion Research Iii Limited | Composition and drug delivery of bisphosphonates |
US9421169B2 (en) | 2009-11-20 | 2016-08-23 | Covidien Lp | Oral dosage forms for delivery of therapeutic agents |
CA2782056C (en) | 2009-11-25 | 2021-03-09 | Arisgen Sa | Mucosal delivery of peptides |
MX2012006265A (es) | 2009-12-03 | 2012-07-25 | Opko Health Inc | Formulaciones disacaridas hipersulfatadas. |
US20110182985A1 (en) * | 2010-01-28 | 2011-07-28 | Coughlan David C | Solid Pharmaceutical Composition with Enhancers and Methods of Preparing thereof |
US9089484B2 (en) * | 2010-03-26 | 2015-07-28 | Merrion Research Iii Limited | Pharmaceutical compositions of selective factor Xa inhibitors for oral administration |
AU2012204213A1 (en) | 2011-01-07 | 2013-06-13 | Merrion Research Iii Limited | Pharmaceutical compositions of iron for oral administration |
WO2016040695A1 (en) | 2014-09-10 | 2016-03-17 | C.R. Bard, Inc. | Protective dressing for skin-placed medical device |
EP3250191B1 (en) | 2015-01-29 | 2024-01-17 | Novo Nordisk A/S | Tablets comprising glp-1 agonist and enteric coating |
Family Cites Families (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3972995A (en) * | 1975-04-14 | 1976-08-03 | American Home Products Corporation | Dosage form |
FR2543145B1 (fr) * | 1983-03-24 | 1986-10-17 | Sanofi Sa | Nouveaux sulfates de xylanes, leur procede de preparation et leur activite anti-thrombotique et hypolipemiante |
DE3323389A1 (de) * | 1983-06-29 | 1985-01-10 | B. Braun Melsungen Ag, 3508 Melsungen | Auf schleimhaeute des mundes, der nase und/oder des rachens wirkende arzneimittel auf der basis von heparin und tensiden |
WO1985002092A1 (en) * | 1983-11-14 | 1985-05-23 | Bio-Mimetics Inc. | Bioadhesive compositions and methods of treatment therewith |
US4963367A (en) * | 1984-04-27 | 1990-10-16 | Medaphore, Inc. | Drug delivery compositions and methods |
FR2572731B1 (fr) * | 1984-11-07 | 1987-03-06 | Sanofi Sa | Nouveaux sulfates de xylanes de bas poids moleculaires, leur procede de preparation et leur activite antithrombotique et hypolipemiante par voie orale |
FR2584728B1 (fr) * | 1985-07-12 | 1987-11-20 | Choay Sa | Procede de sulfatation de glycosaminoglycanes et de leurs fragments |
DE3787996T2 (de) * | 1986-05-16 | 1994-03-03 | Italfarmaco Spa | Heparine, frei von E.D.T.A., Fraktionen und Fragmente von Heparin, Verfahren zu deren Herstellung und pharmazeutische Zusammensetzungen, welche diese enthalten. |
US4855142A (en) * | 1987-02-27 | 1989-08-08 | Ciba-Geigy Corporation | Pharmaceutical plaster |
FR2614026B1 (fr) * | 1987-04-16 | 1992-04-17 | Sanofi Sa | Heparines de bas poids moleculaire, a structure reguliere, leur preparation et leurs applications biologiques |
US5273757A (en) * | 1987-09-01 | 1993-12-28 | Lts Lohmann Therapie-Systeme Gmbh & Co. Kg | Apparatus for the delivery of substances, processes for the production thereof and use thereof |
US4849224A (en) * | 1987-11-12 | 1989-07-18 | Theratech Inc. | Device for administering an active agent to the skin or mucosa |
EP0337327A1 (en) * | 1988-04-09 | 1989-10-18 | Bioiberica, S.A. | Process for the preparation of new oligosaccharide fractions by controlled chemical depolimerization of heparin |
KR0186037B1 (ko) * | 1989-11-03 | 1999-05-01 | 더블유. 죠오지 메레디스 | 바이오접착제 조성물 및 패치 |
IT1243300B (it) * | 1990-12-20 | 1994-05-26 | Fidia Spa | Derivati dell'eparina |
US5113860A (en) * | 1991-03-15 | 1992-05-19 | Minnesota Mining And Manufacturing Company | Non-invasive transmucosal drug level monitoring method |
SE9200951D0 (sv) * | 1992-03-27 | 1992-03-27 | Kabi Pharmacia Ab | Pharmaceutical composition containing a defined lipid system |
US5346701A (en) * | 1993-02-22 | 1994-09-13 | Theratech, Inc. | Transmucosal delivery of macromolecular drugs |
US5639469A (en) * | 1994-06-15 | 1997-06-17 | Minnesota Mining And Manufacturing Company | Transmucosal delivery system |
-
1994
- 1994-06-15 US US08/259,873 patent/US5639469A/en not_active Expired - Lifetime
-
1995
- 1995-06-09 WO PCT/US1995/007358 patent/WO1995034286A1/en not_active Application Discontinuation
- 1995-06-09 JP JP8502353A patent/JPH10501816A/ja not_active Ceased
- 1995-06-09 AU AU27022/95A patent/AU694695B2/en not_active Ceased
- 1995-06-09 EP EP95922283A patent/EP0804154A1/en not_active Ceased
- 1995-06-09 CA CA002190778A patent/CA2190778C/en not_active Expired - Fee Related
- 1995-06-09 NZ NZ288104A patent/NZ288104A/xx unknown
-
1997
- 1997-06-17 US US08/877,397 patent/US5908637A/en not_active Expired - Lifetime
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPWO2019004088A1 (ja) * | 2017-06-27 | 2020-04-23 | 株式会社バイオセレンタック | 粘膜付着性経口製剤 |
Also Published As
Publication number | Publication date |
---|---|
US5639469A (en) | 1997-06-17 |
AU2702295A (en) | 1996-01-05 |
CA2190778A1 (en) | 1995-12-21 |
WO1995034286A1 (en) | 1995-12-21 |
NZ288104A (en) | 1998-12-23 |
EP0804154A1 (en) | 1997-11-05 |
AU694695B2 (en) | 1998-07-23 |
US5908637A (en) | 1999-06-01 |
CA2190778C (en) | 2006-12-19 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JPH10501816A (ja) | 経粘膜輸送システム | |
US5110605A (en) | Calcium polycarbophil-alginate controlled release composition and method | |
JP2795749B2 (ja) | 高分子薬物の粘膜透過による投与 | |
MIYAzAKI et al. | Chitosan and sodium alginate based bioadhesive tablets for intraoral drug delivery | |
Burgalassi et al. | Development and in vitro/in vivo testing of mucoadhesive buccal patches releasing benzydamine and lidocaine | |
Jiménez-castellanos et al. | Mucoadhesive drug delivery systems | |
Ahuja et al. | Mucoadhesive drug delivery systems | |
US5102666A (en) | Calcium polycarbophil controlled release composition and method | |
US4983392A (en) | Bioadhesive compositions and methods of treatment therewith | |
EP1108423B1 (en) | Powdery pernasal compositions | |
Nakamura et al. | In vitro and in vivo nasal mucoadhesion of some water-soluble polymers | |
EP0163696B1 (en) | Use of a bioadhesive | |
US6696085B2 (en) | Use of an acrylic type polymer as disintegrating agent | |
EP1997478B1 (en) | Liquid formulations for the prevention and treatment of mucosal diseases and disorders | |
EP0451433A1 (en) | Composition of a bioadhesive sustained delivery carrier for drug administration | |
EP0497956B1 (en) | Controlled release formulations | |
US20240122850A1 (en) | Vaginal Hydrogel for Delivery of Therapeutics | |
EP0136006B1 (en) | Pharmaceutical compositions | |
EP0429156B1 (en) | Method of moisturizing tissue and composition | |
Saleem et al. | Formulation and evaluation of mucoadhesive buccal tablets of sumatriptan succinate | |
RU2473327C2 (ru) | Композиция для борьбы с эпистаксисом | |
ES2228597T3 (es) | Laxante formador de masa sintetico. | |
CN117695438A (zh) | 一种促进组织修复的增强水凝胶材料、水凝胶膜贴及制备方法 | |
Liu et al. | Delivery of a calcium channel blocker through buccal mucosa from matrix type mucoadhesive films for improved cardiac drug delivery | |
ATTWOOD | Pharmaceutical Application of Biomedical Polymers. Part XXXV. Chitosan and Sodium Alginate Based Bioadhesive Tablets for Intraoral Drug Delivery. |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20060104 |
|
A72 | Notification of change in name of applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A721 Effective date: 20060104 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20060425 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20060724 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20060904 |
|
A313 | Final decision of rejection without a dissenting response from the applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A313 Effective date: 20061218 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20070130 |