CN102198140A - 具有改进的药物代谢动力学特性的药物 - Google Patents
具有改进的药物代谢动力学特性的药物 Download PDFInfo
- Publication number
- CN102198140A CN102198140A CN2011100785380A CN201110078538A CN102198140A CN 102198140 A CN102198140 A CN 102198140A CN 2011100785380 A CN2011100785380 A CN 2011100785380A CN 201110078538 A CN201110078538 A CN 201110078538A CN 102198140 A CN102198140 A CN 102198140A
- Authority
- CN
- China
- Prior art keywords
- vardenafil
- pharmaceutical preparation
- tablet
- acid
- oral cavity
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- SECKRCOLJRRGGV-UHFFFAOYSA-N Vardenafil Chemical compound CCCC1=NC(C)=C(C(N=2)=O)N1NC=2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(CC)CC1 SECKRCOLJRRGGV-UHFFFAOYSA-N 0.000 claims abstract description 68
- 229960002381 vardenafil Drugs 0.000 claims abstract description 65
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 37
- 210000000214 mouth Anatomy 0.000 claims description 26
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 10
- CUGZEDSDRBMZMY-UHFFFAOYSA-N trihydrate;hydrochloride Chemical compound O.O.O.Cl CUGZEDSDRBMZMY-UHFFFAOYSA-N 0.000 claims description 10
- 238000002156 mixing Methods 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 6
- 235000002639 sodium chloride Nutrition 0.000 claims description 6
- 150000003839 salts Chemical group 0.000 claims description 5
- 150000005846 sugar alcohols Chemical class 0.000 claims description 4
- 239000000463 material Substances 0.000 claims description 3
- 239000002245 particle Substances 0.000 claims description 3
- 238000012856 packing Methods 0.000 claims 1
- 238000009512 pharmaceutical packaging Methods 0.000 claims 1
- 230000036470 plasma concentration Effects 0.000 abstract description 19
- 239000000203 mixture Substances 0.000 abstract description 14
- 238000002360 preparation method Methods 0.000 abstract description 11
- 238000000034 method Methods 0.000 abstract description 9
- 238000009472 formulation Methods 0.000 abstract description 2
- 239000002547 new drug Substances 0.000 abstract 1
- 239000003826 tablet Substances 0.000 description 45
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 20
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 16
- 239000004615 ingredient Substances 0.000 description 15
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 230000000052 comparative effect Effects 0.000 description 10
- 235000019359 magnesium stearate Nutrition 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 8
- -1 polyethylene pyrrolidone Polymers 0.000 description 8
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 7
- 235000013599 spices Nutrition 0.000 description 7
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 6
- 230000009747 swallowing Effects 0.000 description 6
- 108010011485 Aspartame Proteins 0.000 description 5
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 5
- 229940099471 Phosphodiesterase inhibitor Drugs 0.000 description 5
- 239000002671 adjuvant Substances 0.000 description 5
- 239000000605 aspartame Substances 0.000 description 5
- 235000010357 aspartame Nutrition 0.000 description 5
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 5
- 229960003438 aspartame Drugs 0.000 description 5
- 238000004090 dissolution Methods 0.000 description 5
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 5
- 239000008108 microcrystalline cellulose Substances 0.000 description 5
- 229940016286 microcrystalline cellulose Drugs 0.000 description 5
- 239000002571 phosphodiesterase inhibitor Substances 0.000 description 5
- 239000000377 silicon dioxide Substances 0.000 description 5
- 235000012239 silicon dioxide Nutrition 0.000 description 5
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 4
- 239000003086 colorant Substances 0.000 description 4
- 239000010408 film Substances 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 239000001329 FEMA 3811 Substances 0.000 description 3
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 239000004376 Sucralose Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000012790 confirmation Methods 0.000 description 3
- 238000004132 cross linking Methods 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 3
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 3
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 3
- 229960003943 hypromellose Drugs 0.000 description 3
- ITVGXXMINPYUHD-CUVHLRMHSA-N neohesperidin dihydrochalcone Chemical compound C1=C(O)C(OC)=CC=C1CCC(=O)C(C(=C1)O)=C(O)C=C1O[C@H]1[C@H](O[C@H]2[C@@H]([C@H](O)[C@@H](O)[C@H](C)O2)O)[C@@H](O)[C@H](O)[C@@H](CO)O1 ITVGXXMINPYUHD-CUVHLRMHSA-N 0.000 description 3
- 229940089953 neohesperidin dihydrochalcone Drugs 0.000 description 3
- 235000010434 neohesperidine DC Nutrition 0.000 description 3
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 description 3
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 3
- 239000001384 succinic acid Substances 0.000 description 3
- 235000019408 sucralose Nutrition 0.000 description 3
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 3
- 239000004408 titanium dioxide Substances 0.000 description 3
- 229920002785 Croscarmellose sodium Polymers 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- 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 2
- 229930195725 Mannitol Natural products 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- JFCQEDHGNNZCLN-UHFFFAOYSA-N glutaric acid Chemical compound OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 2
- 238000000227 grinding Methods 0.000 description 2
- 239000004310 lactic acid Substances 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 239000007968 orange flavor Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000007873 sieving Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000006190 sub-lingual tablet Substances 0.000 description 2
- 229940098466 sublingual tablet Drugs 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000010409 thin film Substances 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
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- UOQHWNPVNXSDDO-UHFFFAOYSA-N 3-bromoimidazo[1,2-a]pyridine-6-carbonitrile Chemical compound C1=CC(C#N)=CN2C(Br)=CN=C21 UOQHWNPVNXSDDO-UHFFFAOYSA-N 0.000 description 1
- XZLIYCQRASOFQM-UHFFFAOYSA-N 5h-imidazo[4,5-d]triazine Chemical compound N1=NC=C2NC=NC2=N1 XZLIYCQRASOFQM-UHFFFAOYSA-N 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-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
- 208000010228 Erectile Dysfunction Diseases 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 241000167880 Hirundinidae Species 0.000 description 1
- 239000011786 L-ascorbyl-6-palmitate Substances 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 239000004902 Softening Agent Substances 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000001361 adipic acid Substances 0.000 description 1
- 235000011037 adipic acid Nutrition 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229940087168 alpha tocopherol Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 235000010385 ascorbyl palmitate Nutrition 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 235000012241 calcium silicate Nutrition 0.000 description 1
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229960005168 croscarmellose Drugs 0.000 description 1
- 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N glycerol 1-phosphate Chemical compound OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 201000001881 impotence Diseases 0.000 description 1
- 229940099563 lactobionic acid Drugs 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 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
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- QLYCZINKZANMRY-UHFFFAOYSA-N methanesulfonic acid;hydrate Chemical compound O.CS(O)(=O)=O.CS(O)(=O)=O QLYCZINKZANMRY-UHFFFAOYSA-N 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 210000002200 mouth mucosa Anatomy 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- YZMHQCWXYHARLS-UHFFFAOYSA-N naphthalene-1,2-disulfonic acid Chemical compound C1=CC=CC2=C(S(O)(=O)=O)C(S(=O)(=O)O)=CC=C21 YZMHQCWXYHARLS-UHFFFAOYSA-N 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229940068977 polysorbate 20 Drugs 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Substances CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229960000984 tocofersolan Drugs 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
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
- 235000004835 α-tocopherol Nutrition 0.000 description 1
Images
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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Physiology (AREA)
- Nutrition Science (AREA)
- Zoology (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Gynecology & Obstetrics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
本发明涉及一种新型伐地那非药物制剂，该药物制剂在口腔中快速崩解，提高生物利用度，并引起平台状的血浆浓度变化过程，及其制备方法。
Description
本案是申请号200680006596.X的分案申请。
技术领域
本申请涉及一种新型伐地那非药物制剂，该药物制剂在口腔中快速崩解，提高生物利用度，并引起平台状的血浆浓度变化过程，及其制备方法。
背景技术
咪唑并三嗪衍生物，如伐地那非，和它们作为cGMP的磷酸二酯酶抑制剂的用途，以及其活性作用谱是已知的(例如WO99/24433)，并可以
商标购得。但是由于伐地那非大约14％的低的生物利用度，以及其血浆浓度在给药伐地那非一小时后急剧下降，使其治疗应用受到损害。低的生物利用度原则上在不同的个体之间会造成高的血浆浓度变化，此外，必须加大剂量，以达到一定的暴露(Exiposition)。口服伐地那非1小时后出现的血浆浓度的急剧下降会引发随后的治疗效果降低的风险。因此，病人必须准确规划自己的服药时间，以有利于实现高的血浆浓度。
鉴于以上原因，要开发新的伐地那非药物制剂，该伐地那非药物制剂解决以上问题之一。申请US 2003/0134861 A1记载了用于经粘膜给药磷酸二酯酶抑制剂的制剂，如含服药物制剂或舌下片。然而，如对比实施例1至3所示，在经口腔粘膜给药伐地那非的情况下，得到非常难以让人满意的血浆浓度，伴随着有效成分的高变化性的、不完全和缓慢的吸收。
此外，还记载了缓释cGMP磷酸二酯酶抑制剂的药物制剂(WO 00/24383)。这种药物制剂可以解决血浆浓度急剧下降的问题。但是缓释药物制剂体积大且对于一部分病人来说很难吞咽。此外他们无法解决伐地那非的生物利用度低的问题。
此外还记载了在口腔中崩解的cGMP磷酸二酯酶抑制剂的药物制剂。US6221402描述了一种尤其用于抗阳萎的有效成分的药物制剂，该药物制剂中的含有效成分核尤其被不溶于唾液的聚合物覆盖。US 2002/0002172中还记载了一种在口腔中崩解的cGMP磷酸二酯酶抑制剂西地那非的药物制剂，其中含有具有较低水溶性的作为游离碱的有效成分。该种在口腔中崩解的药物制剂具有让病人容易服用的优点，因为该药物制剂在口腔中即已崩解。但是，该种药物制剂既不能提高生物利用度，其血浆浓度也不能保持很长时间。因为病人在短时间后将崩解的药物制剂吞咽下去，而在传统的吞服片剂情况下活性物质到了胃里才开始溶解。因此，在最佳的状况下，会出现和给药传统吞服片剂后相似的生物利用度。
现在在口腔中崩解的伐地那非药物制剂中，令人惊奇地发现，提高了生物利用度，并引起平台状的血浆浓度变化过程。与常规的用水吞咽的片剂相比，根据本发明的制剂具有明显地提高的生物利用度。其中，在一个时间段内实现了更高的血浆浓度，若是常规吞服片剂则在该时间段内已经出现了血浆浓度的下降，比如在达到最大血浆浓度值后的0到5小时内。结果在相同剂量时，在这段时间会达到更好的效果。在给药特别快速崩解和释放的药物制剂几个小时后特别是血浆浓度的提高，会有意想不到的发现，因为通过加快有效成分的崩解可能会出现快速的增长和伐地那非的血浆浓度的更快下降。
附图说明
在给药10mg实施例6的根据本发明制剂(黑色三角)和作为标准片剂(空心圆)的伐地那非后的平均血浆浓度曲线。
发明内容
因此，该发明的主题是含伐地那非的药物制剂，其特征在于，所用的伐地那非形式在少量的水性液体中的溶解度足够高，其在口腔中崩解的溶解速度也足够快。已经发现，当在25℃，至少80％的伐地那非剂量从所用物质形式(例如盐或与酸的混合物)溶解于10毫升生理盐水中时，和当药物制剂的释放率在900毫升的生理盐水中在开始5分钟内至少达到70％时(37℃，USP叶片搅拌设备，50转/分钟)，可以确保实现。
本发明的另一方面是，针对本发明制剂的最佳服用方法。通常，经粘膜药物制剂会尽可能长时间和紧密地与粘膜接触，如通过将含有效成分的薄膜粘贴到口腔粘膜上。若病人不愿意这样或这种做法不可行，则一般使用借助一些液体吞服片剂。已经发现，两种做法都会影响伐地那非的可实现生物利用度。与之相反，当病人将根据本发明的药物制剂放在口腔中，等待其在口中崩解，然后将产生的溶液或悬浮液吞下时，可以实现伐地那非生物利用度的提高。因此，本发明的药物制剂要包装在初始包装，如塑料瓶或泡状包装中，并配备标签或包装纸，其中注明上述服用方法。
特别地，为了制备本发明的制剂，含有伐地那非与酸的盐形式的伐地那非。该盐中可以含有溶剂或不含溶剂，并以不同多态形式存在。例如盐酸伐地那非三水合物，伐地那非二甲磺酸盐单水合物或伐地那非单甲磺酸盐。还可以是伐地那非与柠檬酸、酒酸、琥珀酸、硫酸、醋酸、己二酸、葡糖酸、谷氨酸、戊二酸、甘油磷酸、乳酸、马来酸、苹果酸、磷酸、乳糖酸、丙二酸、萘磺酸、萘二磺酸或甲苯磺酸。另外，还可行的是，通过在药物制剂中总地处理伐地那非和酸得到本发明的制剂。在这种情况下，在口腔中崩解的过程中会产生相应的盐。当药物制剂中的伐地那非盐以研磨的、非结晶的或已经溶解的形式容纳时，有利于达到根据本发明的溶解速度。优选的是伐地那非或伐地那非盐以微粉化形式添加，其平均颗粒大小小于20μm。在可以快速在口腔中崩解的药物制剂中，伐地那非或伐地那非盐的含量优选为0.8％到25％(以伐地那非计算)。
伐地那非盐以已知的方式转变成在口腔中快速崩解药物制剂。在口腔中快速崩解的药物制剂意指该药物制剂的崩解时间少于3分钟(根据欧洲药典中的方法)，最好是少于1分钟。合适的是，将有效成分和糖、糖醇、崩解剂或其他有助于崩解的物质，以及其他的辅料如表面活性剂，润滑剂、控流剂(Flie βregulierungsmittel)、调味剂、色料或填充物质向混合，并在压片机上压制。这里优选的是使用糖醇，如甘露醇或山梨醇，特别是以40％到99％(基于最终片剂)浓度。另外，伐地那非盐也可以与辅料如糖、糖醇、聚合物或表面活性剂一起溶解或悬浮在水性溶剂中，将该溶液和悬浮液计量添加到泡状碗
并进行冻干。另外，同样可以将伐地那非盐与辅料如膜形成剂、软化剂、调味剂和色料一同溶解或悬浮在有机溶剂中，并将其加工成膜。用可熔融薄膜制剂也可以在无溶剂的条件下成膜。制备后将该膜切成单次剂量的小块。
具体实施方式
对比实施例1
用于经口腔粘膜给药的药物制剂的盐酸伐地那非的少量和缓慢吸收
将30mg的盐酸伐地那非，54mg的对羟基苯甲酸甲酯，6mg的对羟基苯甲酸丙酯和9g的蔗糖溶解在约20g水中。借助20％乳酸溶液将pH调节到3.9，再加水至总量33.405g。向十位先证者各舌下施加11.97g该溶液(对应于10mg伐地那非)15分钟。作为对比，以交叉实验方法，给药常见的借助水吞服的片剂，该片剂由下列成分组成：11.852mg的盐酸伐地那非三水合物(对应于10mg伐地那非)，105.023mg的微晶纤维素，6.25mg的交联聚乙烯基吡咯烷酮，0.625mg的胶体二氧化硅，1.25mg的硬脂酸镁，2.391mg的羟丙甲纤维素，0.797mg的聚乙二醇400，0.653mg的二氧化钛，0.133mg的黄色氧化铁和0.011mg的红色氧化铁。与这种作为基准的标准片剂相比，舌下给药的溶液的相对的生物利用度只有24.6％。
对比实施例2
在经口腔粘膜给药的药物制剂中伐地那非的少量和缓慢吸收将2g的伐地那非，0.1g的棕榈酸维生素C酯，0.5g的α-生育酚和7.8g的氨丁三醇溶解在250g的聚山梨酯20，400g的1，2-丙二醇，250g的96％乙醇，35.8g 1M的盐酸和52.6g的水中。向10位先证者各舌下给药5ml的该溶液(对应于10mg伐地那非)15分钟。在交叉对比中，先证者得到了作为参比的在对比实施例1中所述用水吞服的10mg的伐地那非片剂，该舌下给药溶液的相对生物利用度为18.9％。
对比实施例3
用于经口腔粘膜给药的药物制剂中伐地那非甲磺酸盐的少量和缓慢吸收
向10位先证者各舌下给药这样的片剂15分钟，该片剂由下列组成：2.39mg的伐地那非单甲磺酸盐，0.0986mg的甲磺酸，20mg的甘露醇，2mg的交联羧甲纤维素钠，25.3mg的微晶纤维素，1mg的硬脂酸镁和0.25mg的高分散二氧化硅。该片剂的崩解时间为4分钟。在交叉对比中，向先证者给药作为参比的在对比实施例1中所述的用水吞服的10mg伐地那非。该舌下片剂的规格化相对利用度为43.9％。
对比实施例4
在非根据本发明的在口腔快速崩解的片剂中生物利用度未获提高
向11位先证者各给药在口腔中快速崩解的片剂，该片剂由10.7mg的伐地那非二水合物(对应于10mg的伐地那非)，0.484mg的黄色氧化铁，0.066mg的红色氧化铁，1.1mg的杏香料，4.4mg的阿斯巴甜，6.6mg的硬脂酸镁和196.65mg的
(SPI公司的市售辅料)组成。这种在口腔中快速崩解的片剂是非根据本发明的，因为在25℃和10ml的生理盐水中，只溶解约0.1mg的伐地那非二水合物(对应于给药剂量的大约1％)，因此没有满足所用有效成分的溶解度标准。与在对比实施例1中实施的参比片剂进行交叉对比，其相对生物利用度为97.3％。
对比实施例5
在非根据本发明的在口腔快速崩解的片剂中生物利用度未获提高
向11位先证者各给药在口腔中崩解的片剂，该片剂由下列组成：10.7mg的伐地那非二水合物(对应于10mg的伐地那非)，5mg的研磨琥珀酸，0.484mg的黄色氧化铁，0.066mg的红色氧化铁，1.1mg的杏香料，4.4mg的阿斯巴甜，6.6mg的硼脂酸镁和191.65mg的
(SPI公司的市售辅料混合物)。这种在口腔中快速崩解的片剂不是根据本发明的，因为它在37℃在900ml的生理盐水中和在转速为50转/分钟的USP叶片搅拌设备中，5分钟内的有效成分释放率只有40％，因此没有满足本发明的溶解速度标准。与对比实施例1中所实施的参比片剂进行交叉对比，其相对生物利用度为101.8％。
实施例6
根据本发明的在口腔中快速崩解的片剂中生物利用度提高的证实
向12位先证者各给药在口腔中快速崩解的片剂，该片剂由下列组成：11.85mg的盐酸伐地那非三水合物，0.55mg的黄色氧化铁，0.075mg的红色氧化铁，0.75mg的杏香料，0.125mg的新橙皮甙二氢查尔酮，2.50mg的阿斯巴甜，0.625mg的高分散二氧化硅，3.125mg的硬脂酸镁和105.4mg的
在25℃，所用有效成分在10ml生理盐水中约溶解10.4mg(对应于8.8mg的伐地那非)，也即剂量的约88％。在37℃，在900ml的生理盐水中，在转速为50转/分钟的USP叶片搅拌设备中，5分钟内的有效成分释放率为73％。借此，满足了本发明的溶解度标准和溶解速度标准。与实施例1中所述的参比片剂相比，其相对生物利用度达141％。相应的药物代谢动力学参数在表1(附录)中给出，平均血浆浓度的变化过程在图1(附录)中对比给出。
实施例7
根据本发明的在口腔中快速崩解的片剂中生物利用度提高的证实
向11位先证者各给药在口腔中快速崩解的片剂，该片剂由下列组成：5.93mg的盐酸伐地那非三水合物，0.352mg的黄色氧化铁，0.048mg的红色氧化铁，0.48mg的杏香料，0.08mg的新橙皮甙二氢查尔酮，1.60mg的阿斯巴甜，0.40mg的高分散二氧化硅，2mg的硬脂酸镁和69.11mg的
所用的有效成分在25℃在10ml的生理盐水中约溶解91％。在37℃和在转速为50转/分钟的USP叶片搅拌设备中在900ml的生理盐水中5分钟内的有效成分释放率为78％。从而实现了本发明的溶解度标准和溶解速度标准。作为对比，在交叉方法中，给药常规的用水吞服的片剂，其由成分组成：5.926mg的盐酸伐地那非三水合物(对应于5mg的伐地那非)，75.419mg的微晶纤维素，4.35mg的交联聚乙烯基吡咯烷酮，0.435mg的胶体二氧化硅，0.87mg的硬脂酸镁，1.664mg的羟丙甲纤维素，0.555mg的聚乙二醇400，0.455mg的二氧化钛，0.092mg的黄色氧化铁和0.007mg的红色氧化铁。与参比片剂相比，其相对生物利用度为149.6％。在给药本发明的片剂直到12小时后，其血浆浓度还高于给药标准片剂的血浆浓度。
实施例8
根据本发明的在口腔中快速崩解的片剂中生物利用度提高的证实
在犁式搅拌器中混合以下成分：697g的微粉化盐酸伐地那非三水合物，500g的色料，该色料是由4.4％黄色氧化铁、0.6％红色氧化铁和95％的
组成的预混合物，30g的杏香料，5g的新橙皮甙二氢查尔酮，100g的阿斯巴甜和3518g的
在转鼓混合器(Freifallmischer)中混合该粉末混合物和25g的高分散二氧化硅，再用0.5mm的筛子筛选。该混合物再与125g的硬脂酸镁在转鼓混合器中混合5分钟。将最终的粉末混合物在压片机上压成重170mg，直径8mm，断裂强度约35N的圆形片剂。作为对比，在交叉方法中，给药常规的用水吞服的片剂，其由下列成分组成：23.705mg的盐酸伐地那非三水合物(对应于20mg的伐地那非)，141.797mg的微晶纤维素，8.85mg的交联聚乙烯基吡咯烷酮，0.885mg的胶体二氧化硅，1.77mg的硬脂酸镁，再用下列涂覆：3.385mg的羟丙甲纤维素，1.128mg的聚乙二醇400，0.925mg的二氧化钛，0.188mg的黄色氧化铁和0.015mg的红色氧化铁。与参比片剂相比，其相对生物利用度为128.2％。
实施例9
下列成分先混合再在轧辊上干燥造粒：18.96kg的盐酸伐地那非三水合物，76.54kg的微晶纤维素，20kg的交联羧甲纤维素和80kg的硅酸钙。这些颗粒与下列成分进一步混合：1kg的高分散二氧化硅，0.5kg的三氯蔗糖(Sucralose)，1kg的粉末状橙味香料和2kg的过筛的硬脂酸镁。最终混合物用圆形压片机压制成直径7mm，质量125mg的片剂。
实施例10
混合以下成分：21.4kg的伐地那非二水合物，60kg的研磨琥珀酸，1.1kg的三氯蔗糖和342.1kg的B2，13.2kg的过筛的硬脂酸镁和2.2kg的粉末状橙味香料。该混合物被压制成直径9mm，质量220mg的片剂(对应于10mg伐地那非剂量)。10mg的伐地那非和30mg的琥珀酸在25℃在10ml生理盐水中完全溶解，在37℃在900ml的生理盐水中和在转速为50转/分钟的USP叶片搅拌设备中，5分钟内的片剂溶解率为90％。
表1
伐地那非的药物代谢动力学参数
tmax为中值(最小值-最大值)
frel为点估计值(90％的置信区间)
Claims (6)
1.一种含有伐地那非的药物制剂，其在口腔中快速崩解，其特征在于：至少80％的伐地那非剂量于25℃从所用物质形式溶解在10毫升生理盐水中，所述药物制剂在USP叶片搅拌设备中以每分钟50转的搅拌速度和37℃的条件下在900毫升生理盐水中在前5分钟内的释放率至少为70％。
2.根据权利要求1所述的药物制剂，其含有与酸形成的盐形式的伐地那非或者伐地那非和酸。
3.根据权利要求2所述的药物制剂，其含有盐酸伐地那非或盐酸伐地那非三水合物。
4.根据权利要求3所述的药物制剂，其含有平均颗粒尺寸小于20μm的微粉化形式的盐酸伐地那非或盐酸伐地那非三水合物。
5.根据权利要求1至4中任一项所述的药物制剂，其含有40％到99％的糖醇。
6.根据权利要求1至5中任一项所述的药物制剂，其放置在具有位于包装纸、标签或包装盒上的注释的药品包装中，该药物制剂被放入口腔中，并在其崩解后咽下。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102005009240.3 | 2005-03-01 | ||
| DE102005009240A DE102005009240A1 (de) | 2005-03-01 | 2005-03-01 | Arzneiformen mit verbesserten pharmakokinetischen Eigenschaften |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200680006596XA Division CN101141950B (zh) | 2005-03-01 | 2006-02-16 | 具有改进的药物代谢动力学特性的药物 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102198140A true CN102198140A (zh) | 2011-09-28 |
| CN102198140B CN102198140B (zh) | 2016-06-08 |
Family
ID=36264023
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200680006596XA Active CN101141950B (zh) | 2005-03-01 | 2006-02-16 | 具有改进的药物代谢动力学特性的药物 |
| CN201110078538.0A Active CN102198140B (zh) | 2005-03-01 | 2006-02-16 | 具有改进的药物代谢动力学特性的药物 |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200680006596XA Active CN101141950B (zh) | 2005-03-01 | 2006-02-16 | 具有改进的药物代谢动力学特性的药物 |
Country Status (39)
| Country | Link |
|---|---|
| US (2) | US8613950B2 (zh) |
| EP (2) | EP1858490B1 (zh) |
| JP (1) | JP5122984B2 (zh) |
| KR (1) | KR101360526B1 (zh) |
| CN (2) | CN101141950B (zh) |
| AR (2) | AR053552A1 (zh) |
| AT (1) | ATE552828T1 (zh) |
| AU (1) | AU2006220100B2 (zh) |
| BR (1) | BRPI0609375A2 (zh) |
| CA (1) | CA2599617C (zh) |
| CR (2) | CR9339A (zh) |
| CY (1) | CY1112874T1 (zh) |
| DE (1) | DE102005009240A1 (zh) |
| DK (1) | DK1858490T3 (zh) |
| DO (1) | DOP2006000049A (zh) |
| ES (1) | ES2384109T3 (zh) |
| GT (1) | GT200600097A (zh) |
| HK (1) | HK1118457A1 (zh) |
| HN (1) | HN2006009000A (zh) |
| HR (1) | HRP20120545T1 (zh) |
| IL (2) | IL185552A (zh) |
| MA (1) | MA29376B1 (zh) |
| MX (1) | MX2007010527A (zh) |
| MY (2) | MY177386A (zh) |
| NO (2) | NO332368B1 (zh) |
| NZ (1) | NZ561004A (zh) |
| PE (2) | PE20061015A1 (zh) |
| PL (1) | PL1858490T3 (zh) |
| PT (1) | PT1858490E (zh) |
| RS (1) | RS52374B (zh) |
| RU (2) | RU2423970C2 (zh) |
| SG (1) | SG160330A1 (zh) |
| SI (1) | SI1858490T1 (zh) |
| TN (1) | TNSN07336A1 (zh) |
| TW (1) | TWI387465B (zh) |
| UA (1) | UA93200C2 (zh) |
| UY (1) | UY29395A1 (zh) |
| WO (1) | WO2006092207A1 (zh) |
| ZA (1) | ZA200707320B (zh) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10232113A1 (de) | 2002-07-16 | 2004-01-29 | Bayer Ag | Vardenafil Hydrochlorid Trihydrat enthaltende Arzneimittel |
| DE102005009241A1 (de) * | 2005-03-01 | 2006-09-07 | Bayer Healthcare Ag | Arzneiformen mit kontrollierter Bioverfügbarkeit |
| DE102005009240A1 (de) * | 2005-03-01 | 2006-09-07 | Bayer Healthcare Ag | Arzneiformen mit verbesserten pharmakokinetischen Eigenschaften |
| FR2906140B1 (fr) * | 2006-09-22 | 2008-12-05 | Philippe Perovitch | Forme galenique pour l'administration par voie trans-muqueuse de principes actifs |
| DE102007027067A1 (de) * | 2007-06-12 | 2008-12-18 | Ratiopharm Gmbh | Verfahren zur Herstellung eines Arzneimittels enthaltend Vardenafil Hydrochlorid Trihydrat |
| DE102009020888A1 (de) * | 2009-05-12 | 2010-11-18 | Ratiopharm Gmbh | Schmelztablette, enthaltend ein Vardenafil-Salz |
| ES2604307T3 (es) | 2009-05-20 | 2017-03-06 | Sumitomo Dainippon Pharma Co., Ltd. | Comprimido de disgregación oral revestido por vía seca |
| GB2497728A (en) | 2011-12-14 | 2013-06-26 | Londonpharma Ltd | Statin formulations for transmucosal delivery |
| GB2497933B (en) * | 2011-12-21 | 2014-12-24 | Londonpharma Ltd | Drug delivery technology |
| CN103372014B (zh) * | 2012-04-26 | 2015-10-21 | 齐鲁制药有限公司 | 一种能快速溶出、稳定的盐酸伐地那非口服固体制剂及其制备方法 |
| CN102727455B (zh) * | 2012-07-03 | 2016-06-29 | 北京科信必成医药科技发展有限公司 | 一种他达那非口腔崩解片及其制备方法 |
| EP3082428A4 (en) | 2013-12-09 | 2017-08-02 | Respira Therapeutics, Inc. | Pde5 inhibitor powder formulations and methods relating thereto |
| CN110193015A (zh) * | 2018-02-27 | 2019-09-03 | 广州朗圣药业有限公司 | 一种盐酸伐地那非口腔崩解片及其制备方法 |
| CN108272765B (zh) * | 2018-04-26 | 2021-02-02 | 江西杏林白马药业股份有限公司 | 含盐酸伐地那非的药物组合物、口崩片及其制备、应用 |
| BR112020021852A2 (pt) | 2018-05-02 | 2021-02-23 | Ferring B.V. | formulações farmacêuticas aperfeiçoadas |
| CN110840851A (zh) * | 2019-08-16 | 2020-02-28 | 天津仁卫生物医药科技有限公司 | 一种盐酸伐地那非口腔崩解片及其制备方法 |
| IT201900020350A1 (it) | 2019-11-05 | 2021-05-05 | Alpex Pharma Sa | Formulazione orodispersibile di vardenafil |
| CA3168680A1 (en) | 2020-01-31 | 2021-08-05 | Nanocopoeia, Llc | Amorphous nilotinib microparticles and uses thereof |
| WO2021222739A1 (en) | 2020-04-30 | 2021-11-04 | Nanocopoeia, Llc | Orally disintegrating tablet comprising amorphous solid dispersion of nilotinib |
| CN114848603B (zh) * | 2022-04-25 | 2023-12-12 | 湖北菲瑞生物药业有限公司 | 一种伐地那非冻干闪释片及其制备工艺 |
Family Cites Families (92)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2705715A (en) * | 1952-10-29 | 1955-04-05 | American Cyanamid Co | Purine compounds and methods of preparing the same |
| GB790762A (en) | 1953-08-28 | 1958-02-19 | Arthur Poole | A hydrate of lignocaine hydrochloride and process for making it |
| CH367510A (de) * | 1957-11-27 | 1963-02-28 | Ciba Geigy | Verfahren zur Herstellung neuer Sulfonamide |
| GB1051734A (zh) * | 1963-01-16 | |||
| GB1042471A (en) * | 1963-01-16 | 1966-09-14 | Ilford Ltd | Penta-azaindenes, their production and use in photographic emulsions |
| US3169129A (en) * | 1963-05-10 | 1965-02-09 | American Cyanamid Co | 2-ortho-hydroxy-phenyl-4-(3h)-quinazolinones |
| USRE26565E (en) * | 1966-03-02 | 1969-04-29 | Table iii | |
| GB1493685A (en) | 1970-12-15 | 1977-11-30 | May & Baker Ltd | 8-azapurinones |
| GB1338235A (en) | 1970-12-15 | 1973-11-21 | May & Baker Ltd | Azapurinones |
| BE791025A (fr) * | 1971-11-19 | 1973-05-07 | Allen & Hanburys Ltd | Composes heterocycliques |
| GB1457873A (en) * | 1973-01-04 | 1976-12-08 | Allen & Hanburys Ltd | Imidazotriazines |
| US4052390A (en) * | 1973-06-12 | 1977-10-04 | May & Baker Limited | Azapurinones |
| US4060615A (en) * | 1976-02-18 | 1977-11-29 | Mead Johnson & Company | 2-Piperazinyl-6,7-dimethoxyquinazolines |
| GB1561345A (en) * | 1976-10-22 | 1980-02-20 | May & Baker Ltd | 8 - azapuring - 6 - ones |
| US4159330A (en) * | 1976-11-02 | 1979-06-26 | Carlo Erba S.P.A. | 2-Disubstituted phenyl-3,4-dihydro-4-oxo-quinazoline derivatives and process for their preparation |
| DK109578A (da) * | 1977-03-25 | 1978-09-26 | Allen & Hanburys Ltd | Fremgangsmaade til fremstilling af heterocycliske forbindelser |
| GB1584461A (en) | 1977-03-25 | 1981-02-11 | Allen & Hanburys Ltd | Imidazotriazines imidazotriazinones and pharmaceutical compositions containing them |
| US4308384A (en) | 1978-09-18 | 1981-12-29 | Glaxo Group Limited | Production of triazinones |
| DE3166627D1 (en) * | 1980-12-12 | 1984-11-15 | Thomae Gmbh Dr K | Pyrimidones, their preparation and medicines containing them |
| US4431440A (en) * | 1981-02-20 | 1984-02-14 | American Cyanamid Company | Method to alter or control the development and/or the life cycle of various plant species |
| JPS60246396A (ja) | 1984-05-22 | 1985-12-06 | Sankyo Co Ltd | 酵素阻害物質ジヒドロデスオキシグリゼオ−ル酸及びその塩類 |
| US4666908A (en) * | 1985-04-05 | 1987-05-19 | Warner-Lambert Company | 5-Substituted pyrazolo[4,3-d]pyrimidine-7-ones and methods of use |
| CA1303037C (en) | 1987-02-02 | 1992-06-09 | Smith Kline & French Laboratories Limited | Purinone derivatives as bronchodilators vasodilators and anti-allergic agents |
| US5254571A (en) * | 1988-04-21 | 1993-10-19 | Smith Kline & French Laboratories Ltd. | Chemical compounds |
| DE68908786T2 (de) * | 1988-06-16 | 1994-03-17 | Smith Kline French Lab | Condensierte Pyrimidinderivate, Verfahren und Zwischenprodukte zu ihrer Herstellung und diese enthaltende pharmazeutische Zubereitungen. |
| GB8814352D0 (en) | 1988-06-16 | 1988-07-20 | Smith Kline French Lab | Chemical compounds |
| US5075310A (en) | 1988-07-01 | 1991-12-24 | Smith Kline & French Laboratories, Ltd. | Pyrimidone derivatives as bronchodilators |
| US4923874A (en) * | 1988-07-21 | 1990-05-08 | G. D. Searle & Co. | Use of 8-azapurin-6-one derivatives for control of hypertension |
| GB8817651D0 (en) | 1988-07-25 | 1988-09-01 | Smith Kline French Lab | Chemical compounds |
| GB8827988D0 (en) | 1988-11-30 | 1989-01-05 | Smith Kline French Lab | Chemical compounds |
| US5574020A (en) * | 1989-09-28 | 1996-11-12 | Eli Lilly And Company | Tilmicosin formulation |
| US4939544A (en) * | 1989-11-01 | 1990-07-03 | Eastman Kodak Company | Mask for radiation emitting panel |
| GB8928346D0 (en) | 1989-12-15 | 1990-02-21 | Smith Kline French Lab | Chemical compounds |
| EP0524180B1 (en) * | 1990-04-11 | 1995-04-26 | The Upjohn Company | Taste masking of ibuprofen by fluid bed coating |
| GB9013750D0 (en) | 1990-06-20 | 1990-08-08 | Pfizer Ltd | Therapeutic agents |
| US5250534A (en) | 1990-06-20 | 1993-10-05 | Pfizer Inc. | Pyrazolopyrimidinone antianginal agents |
| GB9114760D0 (en) | 1991-07-09 | 1991-08-28 | Pfizer Ltd | Therapeutic agents |
| US5316906A (en) * | 1991-08-23 | 1994-05-31 | Molecular Probes, Inc. | Enzymatic analysis using substrates that yield fluorescent precipitates |
| GB9119704D0 (en) | 1991-09-14 | 1991-10-30 | Pfizer Ltd | Therapeutic agents |
| GB9126260D0 (en) * | 1991-12-11 | 1992-02-12 | Pfizer Ltd | Therapeutic agents |
| US5294612A (en) * | 1992-03-30 | 1994-03-15 | Sterling Winthrop Inc. | 6-heterocyclyl pyrazolo [3,4-d]pyrimidin-4-ones and compositions and method of use thereof |
| US5734053A (en) * | 1992-06-26 | 1998-03-31 | Pfizer Inc | Purinone antianginal agents |
| GB9218322D0 (en) * | 1992-08-28 | 1992-10-14 | Pfizer Ltd | Therapeutic agents |
| GB9311920D0 (en) | 1993-06-09 | 1993-07-28 | Pfizer Ltd | Therapeutic agents |
| GB9315017D0 (en) | 1993-07-20 | 1993-09-01 | Glaxo Lab Sa | Chemical compounds |
| EP0669324A4 (en) | 1993-09-10 | 1996-04-03 | Eisai Co Ltd | CHINAZOLIN DERIVATIVES. |
| US6143746A (en) * | 1994-01-21 | 2000-11-07 | Icos Corporation | Tetracyclic cyclic GMP-specific phosphodiesterase inhibitors, process of preparation and use |
| US5556847A (en) * | 1994-10-27 | 1996-09-17 | Duquesne University Of The Holy Ghost | Methods of effecting memory enhancement mediated by steroid sulfatase inhibitors |
| GB9423911D0 (en) * | 1994-11-26 | 1995-01-11 | Pfizer Ltd | Therapeutic agents |
| GB9612514D0 (en) | 1996-06-14 | 1996-08-14 | Pfizer Ltd | Novel process |
| US6548490B1 (en) | 1997-10-28 | 2003-04-15 | Vivus, Inc. | Transmucosal administration of phosphodiesterase inhibitors for the treatment of erectile dysfunction |
| CN100430396C (zh) * | 1997-11-12 | 2008-11-05 | 拜耳医药保健股份公司 | 用作磷酸二酯酶抑制剂的2-苯基取代的咪唑并三嗪酮 |
| US6221402B1 (en) * | 1997-11-20 | 2001-04-24 | Pfizer Inc. | Rapidly releasing and taste-masking pharmaceutical dosage form |
| GT199900061A (es) | 1998-05-15 | 2000-10-14 | Pfizer | Formulaciones farmaceuticas. |
| DE19827640A1 (de) * | 1998-06-20 | 1999-12-23 | Bayer Ag | 7-Alkyl- und Cycloalkyl-substituierte Imidazotriazinone |
| US6743443B1 (en) * | 1998-10-05 | 2004-06-01 | Eisai Co., Ltd. | Tablets immediately disintegrating in the oral cavity |
| UA67802C2 (uk) * | 1998-10-23 | 2004-07-15 | Пфайзер Рісьоч Енд Дівелепмент Компані, Н.В./С.А. | Фармацевтична композиція з контрольованим вивільненням інгібітора цгмф фде-5 (варіанти), спосіб її одержання та спосіб лікування еректильної дисфункції |
| FR2785538B1 (fr) | 1998-11-06 | 2004-04-09 | Prographarm Laboratoires | Comprime a delitement rapide perfectionne |
| WO2000057857A1 (en) * | 1999-03-25 | 2000-10-05 | Yuhan Corporation | Rapidly disintegrable tablet for oral administration |
| IL137429A0 (en) | 1999-07-28 | 2001-07-24 | Pfizer Prod Inc | Methods and compsitions for treating diseases and conditions of the eye |
| US6284270B1 (en) * | 1999-08-04 | 2001-09-04 | Drugtech Corporation | Means for creating a mass having structural integrity |
| US6075028A (en) * | 1999-09-23 | 2000-06-13 | Graham; Richard | Method of treating Tourette's syndrome and related CNS disorders |
| US6503908B1 (en) * | 1999-10-11 | 2003-01-07 | Pfizer Inc | Pharmaceutically active compounds |
| TWI224966B (en) | 1999-11-02 | 2004-12-11 | Pfizer | Pharmaceutical composition (I) useful for treating or preventing pulmonary hypertension in a patient |
| CA2395548A1 (en) * | 1999-12-24 | 2001-07-05 | Bayer Aktiengesellschaft | Imidazo 1,3,5 triazinones and the use thereof |
| US6774128B2 (en) * | 2000-04-19 | 2004-08-10 | Johns Hopkins University | Methods for prevention and treatment of gastrointestinal disorders |
| AU2001278673A1 (en) * | 2000-10-30 | 2002-05-15 | Lupin Limited | Rapidly disintegrating sustained release cefuroxime axetil composition |
| CN100372536C (zh) * | 2001-02-15 | 2008-03-05 | 田边三菱制药株式会社 | 在口腔中迅速崩解的片剂 |
| DE10118306A1 (de) * | 2001-04-12 | 2002-10-17 | Bayer Ag | Imidazotriazinonhaltige Zusammensetzungen zur nasalen Applikation |
| FR2823668B1 (fr) | 2001-04-20 | 2004-02-27 | Ethypharm Lab Prod Ethiques | Comprimes effervescents orodispersibles |
| WO2002089808A1 (de) * | 2001-05-09 | 2002-11-14 | Bayer Healthcare Ag | Neue verwendung von 2-phenyl-substituierten imidazotriazinonen |
| PL361452A1 (en) | 2001-07-27 | 2004-10-04 | Yamanouchi Pharmaceutical Co.Ltd. | Compositions containing sustained-release fine grains for tablets quickly disintegrable in the oral cavity and process for producing the same |
| FR2831820B1 (fr) | 2001-11-05 | 2004-08-20 | Ethypharm Sa | Comprime orodispersible presentant une grande homogeneite et son procede de preparation |
| US7118765B2 (en) * | 2001-12-17 | 2006-10-10 | Spi Pharma, Inc. | Co-processed carbohydrate system as a quick-dissolve matrix for solid dosage forms |
| US20030175346A1 (en) * | 2002-02-01 | 2003-09-18 | Anne Billotte | Osmotic delivery system |
| US7939102B2 (en) * | 2002-06-07 | 2011-05-10 | Torrent Pharmaceuticals Ltd. | Controlled release formulation of lamotrigine |
| DE10232113A1 (de) * | 2002-07-16 | 2004-01-29 | Bayer Ag | Vardenafil Hydrochlorid Trihydrat enthaltende Arzneimittel |
| SE0202365D0 (sv) | 2002-08-05 | 2002-08-05 | Pharmacia Ab | New formulation and use thereof |
| GB0219516D0 (en) | 2002-08-21 | 2002-10-02 | Phoqus Ltd | Fast dissolving and taste masked oral dosage form comprising sildenafil |
| US20040115287A1 (en) * | 2002-12-17 | 2004-06-17 | Lipocine, Inc. | Hydrophobic active agent compositions and methods |
| KR101125268B1 (ko) | 2003-06-06 | 2012-04-23 | 에띠팜 | 구강 분산성 다중층 정제 |
| DE10325813B4 (de) | 2003-06-06 | 2007-12-20 | Universitätsklinikum Freiburg | Prophylaxe und/oder Therapie bei der portalen Hypertonie |
| JP3841804B2 (ja) | 2003-10-15 | 2006-11-08 | 富士化学工業株式会社 | 口腔内速崩壊性錠剤用の組成物 |
| RU2388466C2 (ru) | 2004-04-27 | 2010-05-10 | Медисинова, Инк. | Производные феноксиалкилкарбоновых кислот при лечении воспалительных заболеваний |
| DE102004023069A1 (de) * | 2004-05-11 | 2005-12-08 | Bayer Healthcare Ag | Neue Darreichungsformen des PDE 5-Inhibitors Vardenafil |
| US9884014B2 (en) | 2004-10-12 | 2018-02-06 | Adare Pharmaceuticals, Inc. | Taste-masked pharmaceutical compositions |
| US20060105039A1 (en) | 2004-10-21 | 2006-05-18 | Jin-Wang Lai | Taste-masked pharmaceutical compositions with gastrosoluble pore-formers |
| US20060105038A1 (en) | 2004-11-12 | 2006-05-18 | Eurand Pharmaceuticals Limited | Taste-masked pharmaceutical compositions prepared by coacervation |
| WO2006058250A2 (en) | 2004-11-24 | 2006-06-01 | Spi Pharma, Inc. | Orally disintegrating compositions |
| DE102005009240A1 (de) | 2005-03-01 | 2006-09-07 | Bayer Healthcare Ag | Arzneiformen mit verbesserten pharmakokinetischen Eigenschaften |
| EP1898879A1 (en) | 2005-06-23 | 2008-03-19 | Schering Corporation | Rapidly absorbing oral formulations of pde5 inhibitors |
| JP5074190B2 (ja) | 2005-09-02 | 2012-11-14 | 富士化学工業株式会社 | 口腔内速崩壊性錠剤 |
-
2005
- 2005-03-01 DE DE102005009240A patent/DE102005009240A1/de not_active Withdrawn
-
2006
- 2006-02-16 KR KR1020077022210A patent/KR101360526B1/ko active IP Right Grant
- 2006-02-16 SI SI200631352T patent/SI1858490T1/sl unknown
- 2006-02-16 PT PT06706994T patent/PT1858490E/pt unknown
- 2006-02-16 AT AT06706994T patent/ATE552828T1/de active
- 2006-02-16 NZ NZ561004A patent/NZ561004A/en unknown
- 2006-02-16 WO PCT/EP2006/001393 patent/WO2006092207A1/de active Application Filing
- 2006-02-16 UA UAA200710870A patent/UA93200C2/ru unknown
- 2006-02-16 MX MX2007010527A patent/MX2007010527A/es active IP Right Grant
- 2006-02-16 BR BRPI0609375-2A patent/BRPI0609375A2/pt not_active Application Discontinuation
- 2006-02-16 US US11/885,019 patent/US8613950B2/en active Active
- 2006-02-16 SG SG201001165-8A patent/SG160330A1/en unknown
- 2006-02-16 EP EP06706994A patent/EP1858490B1/de active Active
- 2006-02-16 JP JP2007557361A patent/JP5122984B2/ja active Active
- 2006-02-16 RU RU2007135982/15A patent/RU2423970C2/ru active
- 2006-02-16 AU AU2006220100A patent/AU2006220100B2/en active Active
- 2006-02-16 CA CA2599617A patent/CA2599617C/en active Active
- 2006-02-16 ES ES06706994T patent/ES2384109T3/es active Active
- 2006-02-16 CN CN200680006596XA patent/CN101141950B/zh active Active
- 2006-02-16 PL PL06706994T patent/PL1858490T3/pl unknown
- 2006-02-16 CN CN201110078538.0A patent/CN102198140B/zh active Active
- 2006-02-16 DK DK06706994.8T patent/DK1858490T3/da active
- 2006-02-16 RS RS20120256A patent/RS52374B/en unknown
- 2006-02-16 EP EP11172872A patent/EP2377523A1/de not_active Withdrawn
- 2006-02-22 DO DO2006000049A patent/DOP2006000049A/es unknown
- 2006-02-24 UY UY29395A patent/UY29395A1/es not_active Application Discontinuation
- 2006-02-27 GT GT200600097A patent/GT200600097A/es unknown
- 2006-02-27 TW TW095106484A patent/TWI387465B/zh active
- 2006-02-28 MY MYPI2011005219A patent/MY177386A/en unknown
- 2006-02-28 MY MYPI20060864A patent/MY148698A/en unknown
- 2006-02-28 PE PE2006000230A patent/PE20061015A1/es not_active Application Discontinuation
- 2006-02-28 PE PE2010000018A patent/PE20100740A1/es not_active Application Discontinuation
- 2006-02-28 AR ARP060100745A patent/AR053552A1/es not_active Application Discontinuation
- 2006-03-01 HN HN2006009000A patent/HN2006009000A/es unknown
-
2007
- 2007-08-27 CR CR9339A patent/CR9339A/es unknown
- 2007-08-28 IL IL185552A patent/IL185552A/en active IP Right Grant
- 2007-08-29 ZA ZA200707320A patent/ZA200707320B/xx unknown
- 2007-08-31 TN TNP2007000336A patent/TNSN07336A1/en unknown
- 2007-09-24 NO NO20074848A patent/NO332368B1/no unknown
- 2007-10-01 MA MA30265A patent/MA29376B1/fr unknown
-
2008
- 2008-09-05 HK HK08109907.5A patent/HK1118457A1/xx unknown
-
2011
- 2011-03-24 RU RU2011111106/15A patent/RU2481110C2/ru active Protection Beyond IP Right Term
-
2012
- 2012-02-24 NO NO20120203A patent/NO344546B1/no unknown
- 2012-06-20 CY CY20121100558T patent/CY1112874T1/el unknown
- 2012-07-05 HR HRP20120545TT patent/HRP20120545T1/hr unknown
-
2013
- 2013-08-07 CR CR20130381A patent/CR20130381A/es unknown
- 2013-12-16 US US14/107,696 patent/US20140186444A1/en not_active Abandoned
-
2016
- 2016-06-30 IL IL246548A patent/IL246548A0/en unknown
-
2018
- 2018-03-20 AR ARP180100644A patent/AR111572A2/es unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101141950B (zh) | 具有改进的药物代谢动力学特性的药物 | |
| CN100353933C (zh) | 快速溶化口服药物制剂 | |
| US10821118B2 (en) | Oral transmucosal drug delivery system | |
| CN1822819A (zh) | 用于减轻或防止尼古丁瘾的口服控释剂型 | |
| TW201114766A (en) | Pharmaceutical composition for a hepatitis C viral protease inhibitor | |
| KR20040058189A (ko) | 관능상 허용가능한 경구내 붕해 조성물 | |
| Singh et al. | Fast dissolving drug delivery systems: formulation, preparation techniques and evaluation | |
| WO2009069139A1 (en) | Dosage form providing an ibuprofen-containing liquid fill | |
| AU2017253367B2 (en) | Orally disintegrating tablets | |
| US20210322306A1 (en) | Oral dissolvable film with high load of polymeric binder | |
| US11179331B1 (en) | Oral soluble film containing sildenafil citrate | |
| WO2016084099A1 (en) | Soft gelatin capsule composition of anti-tussive agents | |
| CN111655229A (zh) | 包含伐地那非的薄膜制剂、其制备方法及其用途 | |
| CA2946701C (en) | Rivaroxaban containing compositions and melt extrusion methods for preparing the same | |
| TW201446287A (zh) | 適合對兒童投予之快速崩解錠及其簡便之製造方法 | |
| CN108883074A (zh) | 含有他达拉非和坦索罗辛并具有改善的稳定性和溶出率的复合胶囊制剂 | |
| AU2011250768A1 (en) | Pharmaceutical forms with improved pharmacokinetic properties | |
| WO2013175508A2 (en) | Stable pharmaceutical composition of aripiprazole |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 1160406 Country of ref document: HK |
|
| ASS | Succession or assignment of patent right |
Owner name: BAYER INTELLECTUAL PROPERTY GMBH Free format text: FORMER OWNER: BAYER PHARMACEUTICALS AG Effective date: 20130328 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| C53 | Correction of patent of invention or patent application | ||
| CB02 | Change of applicant information |
Address after: Berlin Applicant after: BAYER PHARMA AG Address before: Berlin Applicant before: Bayer Schering Pharma AG |
|
| COR | Change of bibliographic data |
Free format text: CORRECT: APPLICANT; FROM: BAYER SCHERING PHARMA AG TO: BAYER PHARMACEUTICALS AG |
|
| TA01 | Transfer of patent application right |
Effective date of registration: 20130328 Address after: German Monheim Applicant after: BAYER INTELLECTUAL PROPERTY GmbH Address before: Berlin Applicant before: BAYER PHARMA AG |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| REG | Reference to a national code |
Ref country code: HK Ref legal event code: GR Ref document number: 1160406 Country of ref document: HK |
|
| CP02 | Change in the address of a patent holder |
Address after: On the Rhine River, Germany Patentee after: BAYER INTELLECTUAL PROPERTY GmbH Address before: Germany Patentee before: BAYER INTELLECTUAL PROPERTY GmbH |
|
| CP02 | Change in the address of a patent holder |