WO2004022038A1 - Chronotherapeutic diltiazem formulations and the administration thereof - Google Patents
Chronotherapeutic diltiazem formulations and the administration thereof Download PDFInfo
- Publication number
- WO2004022038A1 WO2004022038A1 PCT/US2003/027895 US0327895W WO2004022038A1 WO 2004022038 A1 WO2004022038 A1 WO 2004022038A1 US 0327895 W US0327895 W US 0327895W WO 2004022038 A1 WO2004022038 A1 WO 2004022038A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- diltiazem
- preparation
- membrane
- patient
- wetting agent
- Prior art date
Links
- 229960004166 diltiazem Drugs 0.000 title claims abstract description 494
- HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 title claims abstract description 492
- 239000000203 mixture Substances 0.000 title claims description 83
- 238000009472 formulation Methods 0.000 title description 40
- 238000002360 preparation method Methods 0.000 claims abstract description 319
- 238000000034 method Methods 0.000 claims abstract description 155
- 208000031225 myocardial ischemia Diseases 0.000 claims abstract description 125
- 150000003839 salts Chemical class 0.000 claims abstract description 79
- 210000004369 blood Anatomy 0.000 claims abstract description 21
- 239000008280 blood Substances 0.000 claims abstract description 21
- 238000013268 sustained release Methods 0.000 claims abstract description 21
- 239000012730 sustained-release form Substances 0.000 claims abstract description 21
- 239000002552 dosage form Substances 0.000 claims abstract description 19
- 238000013270 controlled release Methods 0.000 claims abstract description 15
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 14
- 230000002459 sustained effect Effects 0.000 claims abstract description 11
- 239000000080 wetting agent Substances 0.000 claims description 163
- 239000012528 membrane Substances 0.000 claims description 161
- 206010002383 Angina Pectoris Diseases 0.000 claims description 129
- 239000011324 bead Substances 0.000 claims description 90
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 claims description 80
- 238000011282 treatment Methods 0.000 claims description 78
- 230000007935 neutral effect Effects 0.000 claims description 67
- 239000012982 microporous membrane Substances 0.000 claims description 64
- 150000004677 hydrates Chemical class 0.000 claims description 61
- 239000004531 microgranule Substances 0.000 claims description 57
- 239000002775 capsule Substances 0.000 claims description 55
- 239000012530 fluid Substances 0.000 claims description 53
- 230000002265 prevention Effects 0.000 claims description 49
- 238000004090 dissolution Methods 0.000 claims description 46
- 229920001577 copolymer Polymers 0.000 claims description 45
- 229920000642 polymer Polymers 0.000 claims description 44
- 229940068196 placebo Drugs 0.000 claims description 42
- 239000000902 placebo Substances 0.000 claims description 42
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 claims description 41
- 238000009792 diffusion process Methods 0.000 claims description 39
- 230000002411 adverse Effects 0.000 claims description 36
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 33
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 30
- 230000002496 gastric effect Effects 0.000 claims description 29
- 229920000058 polyacrylate Polymers 0.000 claims description 29
- 210000001035 gastrointestinal tract Anatomy 0.000 claims description 28
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 28
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 27
- 229920003169 water-soluble polymer Polymers 0.000 claims description 27
- 230000008901 benefit Effects 0.000 claims description 20
- 239000002609 medium Substances 0.000 claims description 20
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 15
- 239000002671 adjuvant Substances 0.000 claims description 15
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 12
- 238000002156 mixing Methods 0.000 claims description 11
- 239000012736 aqueous medium Substances 0.000 claims description 10
- -1 2-methyl-l- oxo-2-propenyl Chemical group 0.000 claims description 9
- SZYSLWCAWVWFLT-UTGHZIEOSA-N [(2s,3s,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)-2-[(2r,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxolan-2-yl]methyl octadecanoate Chemical compound O([C@@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@]1(COC(=O)CCCCCCCCCCCCCCCCC)O[C@H](CO)[C@@H](O)[C@@H]1O SZYSLWCAWVWFLT-UTGHZIEOSA-N 0.000 claims description 9
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 9
- 229920000053 polysorbate 80 Polymers 0.000 claims description 9
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 239000000454 talc Substances 0.000 claims description 8
- 229910052623 talc Inorganic materials 0.000 claims description 8
- FEDJGPQLLNQAIY-UHFFFAOYSA-N 2-[(6-oxo-1h-pyridazin-3-yl)oxy]acetic acid Chemical compound OC(=O)COC=1C=CC(=O)NN=1 FEDJGPQLLNQAIY-UHFFFAOYSA-N 0.000 claims description 7
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 7
- 229960005316 diltiazem hydrochloride Drugs 0.000 claims description 7
- 230000000968 intestinal effect Effects 0.000 claims description 7
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 7
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 7
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 7
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims description 7
- 229940068968 polysorbate 80 Drugs 0.000 claims description 7
- 229920003081 Povidone K 30 Polymers 0.000 claims description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 6
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 6
- 239000000839 emulsion Substances 0.000 claims description 6
- 239000000194 fatty acid Substances 0.000 claims description 6
- 229930195729 fatty acid Natural products 0.000 claims description 6
- 230000007246 mechanism Effects 0.000 claims description 6
- 239000004014 plasticizer Substances 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 6
- 239000008213 purified water Substances 0.000 claims description 6
- 229940031705 hydroxypropyl methylcellulose 2910 Drugs 0.000 claims description 5
- 150000007524 organic acids Chemical group 0.000 claims description 5
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 4
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 claims description 4
- 230000000887 hydrating effect Effects 0.000 claims description 4
- 239000011148 porous material Substances 0.000 claims description 4
- 230000035939 shock Effects 0.000 claims description 4
- 229920000136 polysorbate Polymers 0.000 claims description 3
- 235000000346 sugar Nutrition 0.000 claims description 3
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 2
- 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 claims 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 claims description 2
- 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 claims description 2
- 229930195725 Mannitol Natural products 0.000 claims description 2
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 claims description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 2
- 229930006000 Sucrose Natural products 0.000 claims description 2
- 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 claims description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 2
- 239000001361 adipic acid Substances 0.000 claims description 2
- 235000011037 adipic acid Nutrition 0.000 claims description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 2
- 239000011668 ascorbic acid Substances 0.000 claims description 2
- 229960005070 ascorbic acid Drugs 0.000 claims description 2
- 235000010323 ascorbic acid Nutrition 0.000 claims description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 claims description 2
- 235000015165 citric acid Nutrition 0.000 claims description 2
- 235000013681 dietary sucrose Nutrition 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 150000004665 fatty acids Chemical class 0.000 claims description 2
- 239000001530 fumaric acid Substances 0.000 claims description 2
- 235000011087 fumaric acid Nutrition 0.000 claims description 2
- 210000000936 intestine Anatomy 0.000 claims description 2
- 239000000787 lecithin Substances 0.000 claims description 2
- 235000010445 lecithin Nutrition 0.000 claims description 2
- 239000001630 malic acid Substances 0.000 claims description 2
- 235000011090 malic acid Nutrition 0.000 claims description 2
- 239000000594 mannitol Substances 0.000 claims description 2
- 235000010355 mannitol Nutrition 0.000 claims description 2
- 229910052751 metal Inorganic materials 0.000 claims description 2
- 239000002184 metal Substances 0.000 claims description 2
- 229950002273 simeticone Drugs 0.000 claims description 2
- 239000000600 sorbitol Substances 0.000 claims description 2
- 235000010356 sorbitol Nutrition 0.000 claims description 2
- 229960004793 sucrose Drugs 0.000 claims description 2
- 150000008163 sugars Chemical class 0.000 claims description 2
- 239000011975 tartaric acid Substances 0.000 claims description 2
- 235000002906 tartaric acid Nutrition 0.000 claims description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 2
- 235000010447 xylitol Nutrition 0.000 claims description 2
- 125000000969 xylosyl group Chemical class C1([C@H](O)[C@@H](O)[C@H](O)CO1)* 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- QUSNBJAOOMFDIB-UHFFFAOYSA-O ethylaminium Chemical compound CC[NH3+] QUSNBJAOOMFDIB-UHFFFAOYSA-O 0.000 claims 1
- 229950004354 phosphorylcholine Drugs 0.000 claims 1
- 235000013305 food Nutrition 0.000 abstract description 23
- 230000002035 prolonged effect Effects 0.000 abstract description 3
- 239000003814 drug Substances 0.000 description 31
- 229940079593 drug Drugs 0.000 description 28
- 239000003826 tablet Substances 0.000 description 28
- 238000012360 testing method Methods 0.000 description 20
- 230000008859 change Effects 0.000 description 18
- HDRXZJPWHTXQRI-BHDTVMLSSA-N diltiazem hydrochloride Chemical compound [Cl-].C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CC[NH+](C)C)C2=CC=CC=C2S1 HDRXZJPWHTXQRI-BHDTVMLSSA-N 0.000 description 17
- 230000000694 effects Effects 0.000 description 13
- 239000008188 pellet Substances 0.000 description 13
- 238000004458 analytical method Methods 0.000 description 12
- 210000002381 plasma Anatomy 0.000 description 12
- 230000036772 blood pressure Effects 0.000 description 11
- 238000011551 log transformation method Methods 0.000 description 11
- 239000001993 wax Substances 0.000 description 11
- 229920003163 Eudragit® NE 30 D Polymers 0.000 description 10
- 238000000540 analysis of variance Methods 0.000 description 10
- 238000009826 distribution Methods 0.000 description 10
- 239000011248 coating agent Substances 0.000 description 9
- 238000000576 coating method Methods 0.000 description 9
- 230000036470 plasma concentration Effects 0.000 description 8
- 206010020772 Hypertension Diseases 0.000 description 7
- 238000010410 dusting Methods 0.000 description 7
- 230000006872 improvement Effects 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 238000013461 design Methods 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 229940079832 sodium starch glycolate Drugs 0.000 description 6
- 229920003109 sodium starch glycolate Polymers 0.000 description 6
- 239000008109 sodium starch glycolate Substances 0.000 description 6
- 238000007619 statistical method Methods 0.000 description 6
- 238000013179 statistical model Methods 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 239000004408 titanium dioxide Substances 0.000 description 6
- 230000036765 blood level Effects 0.000 description 5
- 230000002354 daily effect Effects 0.000 description 5
- 231100000673 dose–response relationship Toxicity 0.000 description 5
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 4
- 229920003152 Eudragit® RS polymer Polymers 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 239000000654 additive Substances 0.000 description 4
- 230000000996 additive effect Effects 0.000 description 4
- 230000007211 cardiovascular event Effects 0.000 description 4
- 230000002060 circadian Effects 0.000 description 4
- FSXVSUSRJXIJHB-UHFFFAOYSA-M ethyl prop-2-enoate;methyl 2-methylprop-2-enoate;trimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]azanium;chloride Chemical compound [Cl-].CCOC(=O)C=C.COC(=O)C(C)=C.CC(=C)C(=O)OCC[N+](C)(C)C FSXVSUSRJXIJHB-UHFFFAOYSA-M 0.000 description 4
- 239000003168 generic drug Substances 0.000 description 4
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 4
- 239000000314 lubricant Substances 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 238000011418 maintenance treatment Methods 0.000 description 4
- 238000012544 monitoring process Methods 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 229940035248 tiazac Drugs 0.000 description 4
- 230000009466 transformation Effects 0.000 description 4
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 3
- 241000282414 Homo sapiens Species 0.000 description 3
- 235000021152 breakfast Nutrition 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- AMTWCFIAVKBGOD-UHFFFAOYSA-N dioxosilane;methoxy-dimethyl-trimethylsilyloxysilane Chemical compound O=[Si]=O.CO[Si](C)(C)O[Si](C)(C)C AMTWCFIAVKBGOD-UHFFFAOYSA-N 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 238000013265 extended release Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 229920003023 plastic Polymers 0.000 description 3
- 239000004033 plastic Substances 0.000 description 3
- 238000012552 review Methods 0.000 description 3
- 229940083037 simethicone Drugs 0.000 description 3
- 238000005507 spraying Methods 0.000 description 3
- 238000012109 statistical procedure Methods 0.000 description 3
- 230000035488 systolic blood pressure Effects 0.000 description 3
- 238000004448 titration Methods 0.000 description 3
- 229960001722 verapamil Drugs 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 229940127291 Calcium channel antagonist Drugs 0.000 description 2
- 229920003151 Eudragit® RL polymer Polymers 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 208000007718 Stable Angina Diseases 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 239000002518 antifoaming agent Substances 0.000 description 2
- 239000000480 calcium channel blocker Substances 0.000 description 2
- 230000027288 circadian rhythm Effects 0.000 description 2
- 239000007891 compressed tablet Substances 0.000 description 2
- 230000035487 diastolic blood pressure Effects 0.000 description 2
- 229940044369 dilacor Drugs 0.000 description 2
- 238000009506 drug dissolution testing Methods 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000004744 fabric Substances 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 2
- 239000010931 gold Substances 0.000 description 2
- 229910052737 gold Inorganic materials 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 238000002483 medication Methods 0.000 description 2
- 239000004200 microcrystalline wax Substances 0.000 description 2
- 235000019808 microcrystalline wax Nutrition 0.000 description 2
- 239000004005 microsphere Substances 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- DNKKLDKIFMDAPT-UHFFFAOYSA-N n,n-dimethylmethanamine;2-methylprop-2-enoic acid Chemical compound CN(C)C.CC(=C)C(O)=O.CC(=C)C(O)=O DNKKLDKIFMDAPT-UHFFFAOYSA-N 0.000 description 2
- 230000035790 physiological processes and functions Effects 0.000 description 2
- 239000000049 pigment Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 238000013105 post hoc analysis Methods 0.000 description 2
- 229940069328 povidone Drugs 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000000630 rising effect Effects 0.000 description 2
- 230000007480 spreading Effects 0.000 description 2
- 238000003892 spreading Methods 0.000 description 2
- 229910001220 stainless steel Inorganic materials 0.000 description 2
- 239000010935 stainless steel Substances 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000012780 transparent material Substances 0.000 description 2
- METKIMKYRPQLGS-GFCCVEGCSA-N (R)-atenolol Chemical compound CC(C)NC[C@@H](O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-GFCCVEGCSA-N 0.000 description 1
- HSUGRBWQSSZJOP-UHFFFAOYSA-N 5-[2-(dimethylamino)ethyl]-2-(4-methoxyphenyl)-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepin-3-yl acetate Chemical compound C1=CC(OC)=CC=C1C1C(OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-UHFFFAOYSA-N 0.000 description 1
- GMRSQCVLGPQPFT-UHFFFAOYSA-N C(=O)=O.[O-2].[O-2].[Ti+4].C(CO)(=O)O Chemical compound C(=O)=O.[O-2].[O-2].[Ti+4].C(CO)(=O)O GMRSQCVLGPQPFT-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 208000007530 Essential hypertension Diseases 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 229920003134 Eudragit® polymer Polymers 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 235000019759 Maize starch Nutrition 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 239000004141 Sodium laurylsulphate Substances 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 206010049418 Sudden Cardiac Death Diseases 0.000 description 1
- 206010042434 Sudden death Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 229960002274 atenolol Drugs 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 229920000704 biodegradable plastic Polymers 0.000 description 1
- 230000037058 blood plasma level Effects 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- DGLFSNZWRYADFC-UHFFFAOYSA-N chembl2334586 Chemical compound C1CCC2=CN=C(N)N=C2C2=C1NC1=CC=C(C#CC(C)(O)C)C=C12 DGLFSNZWRYADFC-UHFFFAOYSA-N 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000011970 concomitant therapy Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000013501 data transformation Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000011978 dissolution method Methods 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 210000002464 muscle smooth vascular Anatomy 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 229920000193 polymethacrylate Polymers 0.000 description 1
- 238000012797 qualification Methods 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000979 retarding effect Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 238000005563 spheronization Methods 0.000 description 1
- 238000000528 statistical test Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000007939 sustained release tablet Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000009492 tablet coating Methods 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 230000005919 time-dependent effect Effects 0.000 description 1
- 229960005196 titanium dioxide Drugs 0.000 description 1
- 235000010215 titanium dioxide Nutrition 0.000 description 1
- 230000002618 waking effect Effects 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 238000009736 wetting Methods 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- 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
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
- A61K9/2081—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets with microcapsules or coated microparticles according to A61K9/50
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
- A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
- A61K9/5047—Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Abstract
Description
Claims
Priority Applications (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
MXPA05002623A MXPA05002623A (en) | 2002-09-09 | 2003-09-09 | Chronotherapeutic diltiazem formulations and the administration thereof. |
AU2003270349A AU2003270349A1 (en) | 2002-09-09 | 2003-09-09 | Chronotherapeutic diltiazem formulations and the administration thereof |
EP03752036A EP1545476A4 (en) | 2002-09-09 | 2003-09-09 | Chronotherapeutic diltiazem formulations and the administration thereof |
JP2004534664A JP2006501261A (en) | 2002-09-09 | 2003-09-09 | Time-treatment diltiazem preparation and its administration |
NZ539174A NZ539174A (en) | 2002-09-09 | 2003-09-09 | Chronotherapeutic diltiazem formulations and the administration thereof |
CA002496837A CA2496837A1 (en) | 2002-09-09 | 2003-09-09 | Chronotherapeutic diltiazem formulations and the administration thereof |
NO20051190A NO20051190L (en) | 2002-09-09 | 2005-03-04 | Chronotherapy diltiazem formulations and administration thereof |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US40887202P | 2002-09-09 | 2002-09-09 | |
US60/408,872 | 2002-09-09 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2004022038A1 true WO2004022038A1 (en) | 2004-03-18 |
Family
ID=31978692
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2003/027895 WO2004022038A1 (en) | 2002-09-09 | 2003-09-09 | Chronotherapeutic diltiazem formulations and the administration thereof |
Country Status (10)
Country | Link |
---|---|
US (2) | US7348028B2 (en) |
EP (1) | EP1545476A4 (en) |
JP (1) | JP2006501261A (en) |
AU (1) | AU2003270349A1 (en) |
CA (1) | CA2496837A1 (en) |
MX (1) | MXPA05002623A (en) |
NO (1) | NO20051190L (en) |
NZ (1) | NZ539174A (en) |
PL (1) | PL375834A1 (en) |
WO (1) | WO2004022038A1 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9730899B2 (en) | 2009-03-18 | 2017-08-15 | Evonik Roehm Gmbh | Controlled release pharmaceutical composition with resistance against the influence of ethanol employing a coating comprising neutral vinyl polymers and excipients |
Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8778395B2 (en) * | 2005-08-11 | 2014-07-15 | Andrx Labs, Llc | Diltiazem controlled release formulation and method of manufacture |
BRPI0924427A2 (en) * | 2009-03-18 | 2016-01-26 | Evonik Roehm Gmbh | controlled release pharmaceutical composition, its preparation process and its use |
US10292937B2 (en) | 2011-03-23 | 2019-05-21 | Ironshore Pharmaceuticals & Development, Inc. | Methods of treatment of attention deficit hyperactivity disorder |
US9283214B2 (en) | 2011-03-23 | 2016-03-15 | Ironshore Pharmaceuticals & Development, Inc. | Compositions for treatment of attention deficit hyperactivity disorder |
US9119809B2 (en) | 2011-03-23 | 2015-09-01 | Ironshore Pharmaceuticals & Development, Inc. | Compositions for treatment of attention deficit hyperactivity disorder |
US9603809B2 (en) | 2011-03-23 | 2017-03-28 | Ironshore Pharmaceuticals & Development, Inc. | Methods of treatment of attention deficit hyperactivity disorder |
US10905652B2 (en) | 2011-03-23 | 2021-02-02 | Ironshore Pharmaceuticals & Development, Inc. | Compositions for treatment of attention deficit hyperactivity disorder |
WO2012129551A1 (en) | 2011-03-23 | 2012-09-27 | Ironshore Pharmaceuticals & Development, Inc. | Methods and compositions for treatment of attention deficit disorder |
US11241391B2 (en) | 2011-03-23 | 2022-02-08 | Ironshore Pharmaceuticals & Development, Inc. | Compositions for treatment of attention deficit hyperactivity disorder |
US8927010B2 (en) | 2011-03-23 | 2015-01-06 | Ironshore Pharmaceuticals & Development, Inc. | Compositions for treatment of attention deficit hyperactivity disorder |
US9498447B2 (en) | 2011-03-23 | 2016-11-22 | Ironshore Pharmaceuticals & Development, Inc. | Compositions for treatment of attention deficit hyperactivity disorder |
US8916588B2 (en) | 2011-03-23 | 2014-12-23 | Ironshore Pharmaceuticals & Development, Inc. | Methods for treatment of attention deficit hyperactivity disorder |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4721619A (en) * | 1983-12-22 | 1988-01-26 | Elan Corporation P.L.C. | Controlled absorption diltiazen pharmaceutical formulation |
US4960596A (en) * | 1987-11-26 | 1990-10-02 | Ethypharm | Slow-release preparation of diltiazem, and a medicine provided thereby |
US5288505A (en) * | 1991-06-26 | 1994-02-22 | Galephar P.R., Inc., Ltd. | Extended release form of diltiazem |
US5529790A (en) * | 1992-12-23 | 1996-06-25 | Kinaform Technology, Inc. | Delayed, sustained-release diltiazem pharmaceutical preparation |
US5616345A (en) * | 1983-12-22 | 1997-04-01 | Elan Corporation Plc | Controlled absorption diltiazen formulation for once-daily administration |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5344657A (en) * | 1988-04-27 | 1994-09-06 | Elf Sanofi | Microbeads of diltiazem, a process for their manufacture and a substained-release pharmaceutical composition containing them |
US5229135A (en) * | 1991-11-22 | 1993-07-20 | Prographarm Laboratories | Sustained release diltiazem formulation |
US6524620B2 (en) * | 1998-07-20 | 2003-02-25 | Andrx Pharmaceuticals, Inc. | Diltiazem controlled release formulation and method of manufacture |
US7108866B1 (en) | 1999-12-10 | 2006-09-19 | Biovall Laboratories International Srl | Chronotherapeutic diltiazem formulations and the administration thereof |
-
2003
- 2003-09-09 US US10/657,752 patent/US7348028B2/en not_active Expired - Fee Related
- 2003-09-09 EP EP03752036A patent/EP1545476A4/en not_active Withdrawn
- 2003-09-09 PL PL03375834A patent/PL375834A1/en not_active Application Discontinuation
- 2003-09-09 AU AU2003270349A patent/AU2003270349A1/en not_active Abandoned
- 2003-09-09 WO PCT/US2003/027895 patent/WO2004022038A1/en active Application Filing
- 2003-09-09 MX MXPA05002623A patent/MXPA05002623A/en not_active Application Discontinuation
- 2003-09-09 JP JP2004534664A patent/JP2006501261A/en active Pending
- 2003-09-09 NZ NZ539174A patent/NZ539174A/en unknown
- 2003-09-09 CA CA002496837A patent/CA2496837A1/en not_active Abandoned
-
2005
- 2005-03-04 NO NO20051190A patent/NO20051190L/en not_active Application Discontinuation
-
2007
- 2007-12-07 US US11/952,343 patent/US20090118256A1/en not_active Abandoned
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4721619A (en) * | 1983-12-22 | 1988-01-26 | Elan Corporation P.L.C. | Controlled absorption diltiazen pharmaceutical formulation |
US5616345A (en) * | 1983-12-22 | 1997-04-01 | Elan Corporation Plc | Controlled absorption diltiazen formulation for once-daily administration |
US4960596A (en) * | 1987-11-26 | 1990-10-02 | Ethypharm | Slow-release preparation of diltiazem, and a medicine provided thereby |
US5288505A (en) * | 1991-06-26 | 1994-02-22 | Galephar P.R., Inc., Ltd. | Extended release form of diltiazem |
US5529790A (en) * | 1992-12-23 | 1996-06-25 | Kinaform Technology, Inc. | Delayed, sustained-release diltiazem pharmaceutical preparation |
Non-Patent Citations (1)
Title |
---|
See also references of EP1545476A4 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9730899B2 (en) | 2009-03-18 | 2017-08-15 | Evonik Roehm Gmbh | Controlled release pharmaceutical composition with resistance against the influence of ethanol employing a coating comprising neutral vinyl polymers and excipients |
Also Published As
Publication number | Publication date |
---|---|
EP1545476A4 (en) | 2008-01-09 |
US7348028B2 (en) | 2008-03-25 |
NO20051190L (en) | 2005-04-08 |
AU2003270349A1 (en) | 2004-03-29 |
NZ539174A (en) | 2007-05-31 |
CA2496837A1 (en) | 2004-03-18 |
EP1545476A1 (en) | 2005-06-29 |
MXPA05002623A (en) | 2005-05-05 |
PL375834A1 (en) | 2005-12-12 |
US20090118256A1 (en) | 2009-05-07 |
US20040176352A1 (en) | 2004-09-09 |
JP2006501261A (en) | 2006-01-12 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20090118256A1 (en) | Chronotherapeutic diltiazem formulations and the administration thereof | |
EP1235562B1 (en) | Chronotherapeutic diltiazem formulations and the administration thereof | |
US9173857B2 (en) | Controlled dose drug delivery system | |
EP2506709B2 (en) | Amantadine compositions and methods of use | |
CA2651890C (en) | Controlled dose drug delivery system | |
JP5687185B2 (en) | Solid oral dosage forms with a two-stage release profile containing multiparticulate systems | |
JP2003528905A (en) | Stavudine-containing sustained release beads | |
CA2566590C (en) | Cronotherapeutic diltiazem formulation and the administration thereof | |
US20060153914A1 (en) | Chronotherapeutic diltiazem formulations and the administration thereof | |
CA2292247A1 (en) | Chronotherapeutic formulations of diltiazem and the administration thereof | |
AU2015202356B2 (en) | Amantadine compositions and methods of use | |
CA2812968A1 (en) | Pharmaceutical formulation containing phenytoin sodium and magnesium stearate |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ OM PH PL PT RO RU SC SD SE SG SK SL TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
WWE | Wipo information: entry into national phase |
Ref document number: 2003270349 Country of ref document: AU |
|
ENP | Entry into the national phase |
Ref document number: 2496837 Country of ref document: CA |
|
WWE | Wipo information: entry into national phase |
Ref document number: 375834 Country of ref document: PL Ref document number: PA/a/2005/002623 Country of ref document: MX Ref document number: 2004534664 Country of ref document: JP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1128/DELNP/2005 Country of ref document: IN |
|
WWE | Wipo information: entry into national phase |
Ref document number: 539174 Country of ref document: NZ |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2003752036 Country of ref document: EP |
|
WWP | Wipo information: published in national office |
Ref document number: 2003752036 Country of ref document: EP |