RU2005127353A - Быстродействующая фармацевтическая композиция - Google Patents
Быстродействующая фармацевтическая композиция Download PDFInfo
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- RU2005127353A RU2005127353A RU2005127353/15A RU2005127353A RU2005127353A RU 2005127353 A RU2005127353 A RU 2005127353A RU 2005127353/15 A RU2005127353/15 A RU 2005127353/15A RU 2005127353 A RU2005127353 A RU 2005127353A RU 2005127353 A RU2005127353 A RU 2005127353A
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- cellulose
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- active agent
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- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract 4
- 239000000203 mixture Substances 0.000 claims abstract 34
- 239000002245 particle Substances 0.000 claims abstract 14
- 239000013543 active substance Substances 0.000 claims abstract 12
- 230000001154 acute effect Effects 0.000 claims abstract 8
- 239000003795 chemical substances by application Substances 0.000 claims abstract 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract 7
- 208000035475 disorder Diseases 0.000 claims abstract 7
- 239000011859 microparticle Substances 0.000 claims abstract 6
- 238000000034 method Methods 0.000 claims abstract 4
- 230000001737 promoting effect Effects 0.000 claims abstract 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract 3
- 230000035587 bioadhesion Effects 0.000 claims abstract 2
- 229920002678 cellulose Polymers 0.000 claims 13
- 239000001913 cellulose Substances 0.000 claims 13
- 235000010980 cellulose Nutrition 0.000 claims 13
- 150000003839 salts Chemical class 0.000 claims 6
- PJMPHNIQZUBGLI-UHFFFAOYSA-N fentanyl Chemical compound C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 PJMPHNIQZUBGLI-UHFFFAOYSA-N 0.000 claims 5
- 229960002428 fentanyl Drugs 0.000 claims 5
- 239000000463 material Substances 0.000 claims 5
- 239000008107 starch Substances 0.000 claims 4
- 235000019698 starch Nutrition 0.000 claims 4
- 229920002472 Starch Polymers 0.000 claims 3
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims 2
- 229920000881 Modified starch Polymers 0.000 claims 2
- TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 claims 2
- 239000001506 calcium phosphate Substances 0.000 claims 2
- RBLGLDWTCZMLRW-UHFFFAOYSA-K dicalcium;phosphate;dihydrate Chemical compound O.O.[Ca+2].[Ca+2].[O-]P([O-])([O-])=O RBLGLDWTCZMLRW-UHFFFAOYSA-K 0.000 claims 2
- 235000019426 modified starch Nutrition 0.000 claims 2
- 230000001314 paroxysmal effect Effects 0.000 claims 2
- 229920000058 polyacrylate Polymers 0.000 claims 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims 2
- 239000004094 surface-active agent Substances 0.000 claims 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 claims 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims 1
- FEBUJFMRSBAMES-UHFFFAOYSA-N 2-[(2-{[3,5-dihydroxy-2-(hydroxymethyl)-6-phosphanyloxan-4-yl]oxy}-3,5-dihydroxy-6-({[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}methyl)oxan-4-yl)oxy]-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl phosphinite Chemical compound OC1C(O)C(O)C(CO)OC1OCC1C(O)C(OC2C(C(OP)C(O)C(CO)O2)O)C(O)C(OC2C(C(CO)OC(P)C2O)O)O1 FEBUJFMRSBAMES-UHFFFAOYSA-N 0.000 claims 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims 1
- 229920001661 Chitosan Polymers 0.000 claims 1
- 229920000896 Ethulose Polymers 0.000 claims 1
- 239000001859 Ethyl hydroxyethyl cellulose Substances 0.000 claims 1
- 108010010803 Gelatin Proteins 0.000 claims 1
- 229920002907 Guar gum Polymers 0.000 claims 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims 1
- 239000004368 Modified starch Substances 0.000 claims 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims 1
- 229920002305 Schizophyllan Polymers 0.000 claims 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims 1
- 229920002125 Sokalan® Polymers 0.000 claims 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 claims 1
- 239000003833 bile salt Substances 0.000 claims 1
- 229940093761 bile salts Drugs 0.000 claims 1
- 239000000227 bioadhesive Substances 0.000 claims 1
- 229910000019 calcium carbonate Inorganic materials 0.000 claims 1
- 229910000389 calcium phosphate Inorganic materials 0.000 claims 1
- 235000011010 calcium phosphates Nutrition 0.000 claims 1
- 229960001631 carbomer Drugs 0.000 claims 1
- 239000001768 carboxy methyl cellulose Substances 0.000 claims 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims 1
- 239000012461 cellulose resin Substances 0.000 claims 1
- 229920003174 cellulose-based polymer Polymers 0.000 claims 1
- 229920001577 copolymer Polymers 0.000 claims 1
- 229920006037 cross link polymer Polymers 0.000 claims 1
- CGMRCMMOCQYHAD-UHFFFAOYSA-K dicalcium;phosphate;hydrate Chemical compound O.[Ca+2].[Ca+2].[O-]P([O-])([O-])=O CGMRCMMOCQYHAD-UHFFFAOYSA-K 0.000 claims 1
- 239000007884 disintegrant Substances 0.000 claims 1
- 239000006185 dispersion Substances 0.000 claims 1
- 235000019326 ethyl hydroxyethyl cellulose Nutrition 0.000 claims 1
- UPBDXRPQPOWRKR-UHFFFAOYSA-N furan-2,5-dione;methoxyethene Chemical compound COC=C.O=C1OC(=O)C=C1 UPBDXRPQPOWRKR-UHFFFAOYSA-N 0.000 claims 1
- 229920000159 gelatin Polymers 0.000 claims 1
- 239000008273 gelatin Substances 0.000 claims 1
- 235000019322 gelatine Nutrition 0.000 claims 1
- 235000011852 gelatine desserts Nutrition 0.000 claims 1
- 239000000665 guar gum Substances 0.000 claims 1
- 235000010417 guar gum Nutrition 0.000 claims 1
- 229960002154 guar gum Drugs 0.000 claims 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims 1
- 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 1
- 229920000609 methyl cellulose Polymers 0.000 claims 1
- 239000001923 methylcellulose Substances 0.000 claims 1
- 235000010981 methylcellulose Nutrition 0.000 claims 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims 1
- 239000008108 microcrystalline cellulose Substances 0.000 claims 1
- 229940016286 microcrystalline cellulose Drugs 0.000 claims 1
- 230000003232 mucoadhesive effect Effects 0.000 claims 1
- 210000004877 mucosa Anatomy 0.000 claims 1
- 229920005615 natural polymer Polymers 0.000 claims 1
- 229920001277 pectin Polymers 0.000 claims 1
- 239000001814 pectin Substances 0.000 claims 1
- 235000010987 pectin Nutrition 0.000 claims 1
- 239000000449 pharmaceutical disintegrant Substances 0.000 claims 1
- 239000008180 pharmaceutical surfactant Substances 0.000 claims 1
- 229920000642 polymer Polymers 0.000 claims 1
- 229920000136 polysorbate Polymers 0.000 claims 1
- 229940068965 polysorbates Drugs 0.000 claims 1
- 235000010413 sodium alginate Nutrition 0.000 claims 1
- 239000000661 sodium alginate Substances 0.000 claims 1
- 229940005550 sodium alginate Drugs 0.000 claims 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims 1
- 229920003179 starch-based polymer Polymers 0.000 claims 1
- 229940078499 tricalcium phosphate Drugs 0.000 claims 1
- 229910000391 tricalcium phosphate Inorganic materials 0.000 claims 1
- 235000019731 tricalcium phosphate Nutrition 0.000 claims 1
- 239000000230 xanthan gum Substances 0.000 claims 1
- 235000010493 xanthan gum Nutrition 0.000 claims 1
- 229920001285 xanthan gum Polymers 0.000 claims 1
- 229940082509 xanthan gum Drugs 0.000 claims 1
Classifications
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- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/167—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface
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- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
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- A—HUMAN NECESSITIES
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- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4468—Non condensed piperidines, e.g. piperocaine having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
-
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- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/2242—Atrial natriuretic factor complex: Atriopeptins, atrial natriuretic protein [ANP]; Cardionatrin, Cardiodilatin
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- A61K9/0043—Nose
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- A61K9/0012—Galenical forms characterised by the site of application
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- 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
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- A—HUMAN NECESSITIES
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- 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
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- 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
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- A—HUMAN NECESSITIES
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- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Physiology (AREA)
- Zoology (AREA)
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- Endocrinology (AREA)
- Hematology (AREA)
- Immunology (AREA)
- Cardiology (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
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- Proteomics, Peptides & Aminoacids (AREA)
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- Obesity (AREA)
- Pulmonology (AREA)
- Heart & Thoracic Surgery (AREA)
- Emergency Medicine (AREA)
- Rheumatology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Claims (24)
1. Фармацевтическая композиция для лечения острых расстройств путем сублингвального или интраназального введения, включающая, по существу, обезвоженную, упорядоченную смесь микрочастиц, по меньшей мере, одного активного агента, применимых к поверхности частиц носителя, в которой указанные частицы существенно больше, чем указанные микрочастицы, и нерастворимы или плохо растворимы в воде, и агент, способствующий биоадгезии и/или мукоадгезии, применимый к поверхности частиц носителя.
2. Композиция по п.1, в которой микрочастицы указанного активного агента или агентов имеют средневзвешенный диаметр менее чем 10 мкм.
3. Композиция по п.1 или 2, в которой средний ситовый диаметр частиц носителя менее чем 750 мкм, предпочтительно от 50 до 500 мкм.
4. Композиция по любому из п.1 или 2, в которой частицы носителя содержат хрупкий материал, который будет легко фрагментироваться при спрессовывании.
5. Композиция по любому из п.1 или 2, в которой частицы носителя содержат от 0,1 до 40 вес.% агента, способствующего био/мукоадгезии, предпочтительно от 2 до 25 вес.% в расчете на всю композицию.
6. Композиция по п.5, в которой агент, способствующий био/мукоадгезии, выбран из группы, состоящей из поперечно-сшитых полимеров, акриловых полимеров, производных целлюлозы, природных полимеров, имеющих био/мукоадгезионные свойства, и их смесей.
7. Композиция по п.6, в которой агент, способствующий био/мукоадгезии, выбран из группы, состоящей из производных целлюлозы и включающей гидроксипропилметилцеллюлозу, гидроксиэтилцеллюлозу, гидроксипропилцеллюлозу, натриевую карбоксиметилцеллюлозу, метилцеллюлозу, этилгидроксиэтилцеллюлозу, карбоксиметилцеллюлозу и модифицированную смолу целлюлозы, кросс-карамеллозы, модифицированного крахмала, акриловых полимеров, включающих карбомер и его производные, полиэтиленоксида, хитозана, желатина, альгината натрия, пектина, склероглюкана, ксантановой смолы, гуаровой смолы, сополимера (метилвиниловый эфир-малеиновый ангидрид) и их смесей.
8. Композиция по любому из п.1 или 2, дополнительно содержащая фармацевтически приемлемый сурфактант в тонкодиспергированной форме и тесно смешанный с активным агентом или агентами.
9. Композиция по п.8, в которой сурфактант присутствует в количестве от 0,5 до 5 вес.% от композиции, предпочтительно от 0,5 до 3 вес.%.
10. Композиция по п.8, в которой сурфактант выбран из группы, состоящей из лаурилсульфата натрия, полисорбатов, солей желчных кислот и их смесей.
11. Композиция по любому из п.1 или 2, в которой частицы носителя содержат, по меньшей мере, один материал, выбранный из группы, состоящей из фармацевтически приемлемых полимеров, фармацевтически приемлемых неорганических солей и их смесей или материала, произведенного совместно из этих материалов.
12. Композиция по п.11, в которой частицы носителя содержат, по меньшей мере, один материал, выбранный из группы, состоящей из целлюлозы, производных целлюлозы, крахмала, производных крахмала, поперечно-сшитых полимеров на основе крахмала или целлюлозы, или поливинилпирролидона.
13. Композиция по п.11, в которой указанные неорганические соли выбраны из группы, состоящей из фосфата кальция, гидрата дикальций фосфата, дигидрата дикальций фосфата, трикальций фосфата, карбоната кальция и сульфата бария.
14. Сублингвальная композиция по любому из п.1 или 2, которая содержит, по меньшей мере, один фармацевтический дезинтегрирующий агент, облегчающий диспергирование частиц носителя с примешанным(и) активным агентом или агентами поверх сублингвальной слизистой оболочки.
15. Сублингвальная композиция по п.14, в которой дезинтегрирующий агент выбран из группы, состоящей из поперечно-сшитого поливинилпирролидона, карбоксиметилкрахмала, природного крахмала, микрокристаллической целлюлозы, целлюлозной смолы и их смесей.
16. Сублингвальная композиция по п.14, в которой дезинтегрирующий агент присутствует в количестве от 1 до 10 вес.% от композиции.
17. Композиция по любому из п.1 или 2, в которой фармацевтически активный агент является фентанилом или его фармацевтически приемлемой солью.
18. Композиция по любому из п.1 или 2 для лечения острых расстройств путем сублингвального введения.
19. Композиция по п.18 для лечения острой или приступообразной боли путем сублингвального введения фентанила или его фармацевтически приемлемой соли.
20. Композиция по любому из п.1 или 2 для лечения острых расстройств путем интраназального введения.
21. Композиция по п.20 для лечения острой или приступообразной боли путем интраназального введения фентанила или его фармацевтически приемлемой соли.
22. Способ лечения острых расстройств, в котором индивидууму, страдающему названным расстройством, вводят сублингвально или интраназально, по крайней мере, одну единичную дозу, по существу, безводной фармацевтической композиции, содержащей эффективное количество, по меньшей мере, одного фармацевтически активного агента в форме микрочастиц, применимых к поверхности частиц носителя, которые в значительной степени больше, чем указанные микрочастицы, и, по существу, нерастворимы или плохо растворимы в воде, и агент, способствующий биоадгезии или мукоадгезии, применимый к поверхности частиц носителя.
23. Способ по п.22, в котором фармацевтически активным агентом является фентанил или его фармацевтически приемлемая соль.
24. Способ по п.23, в котором фентанил вводят в количестве от 0,025 до 10 мг, предпочтительно от 0,05 до 2 мг на единичную дозу.
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| US44385703P | 2003-01-31 | 2003-01-31 | |
| US60/443,857 | 2003-01-31 |
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| RU2005127353A true RU2005127353A (ru) | 2006-06-10 |
| RU2345791C2 RU2345791C2 (ru) | 2009-02-10 |
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| RU2005127353/15A RU2345791C2 (ru) | 2003-01-31 | 2004-01-15 | Быстродействующая фармацевтическая композиция |
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| EP (1) | EP1587514B3 (ru) |
| JP (1) | JP2006516616A (ru) |
| KR (1) | KR20050096950A (ru) |
| CN (1) | CN100581586C (ru) |
| AT (1) | ATE329594T1 (ru) |
| AU (1) | AU2004208644B2 (ru) |
| CA (1) | CA2512559A1 (ru) |
| CY (1) | CY1106154T1 (ru) |
| DE (1) | DE602004001209T3 (ru) |
| DK (1) | DK1587514T3 (ru) |
| ES (1) | ES2270335T7 (ru) |
| HK (1) | HK1080387A1 (ru) |
| MX (1) | MXPA05008140A (ru) |
| NO (1) | NO20053277L (ru) |
| NZ (1) | NZ541167A (ru) |
| PL (1) | PL211224B1 (ru) |
| PT (1) | PT1587514E (ru) |
| RU (1) | RU2345791C2 (ru) |
| SI (1) | SI1587514T1 (ru) |
| WO (1) | WO2004067004A1 (ru) |
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Also Published As
| Publication number | Publication date |
|---|---|
| RU2345791C2 (ru) | 2009-02-10 |
| EP1587514B3 (en) | 2011-06-22 |
| ATE329594T1 (de) | 2006-07-15 |
| ES2270335T3 (es) | 2007-04-01 |
| HK1080387A1 (en) | 2006-04-28 |
| PL211224B1 (pl) | 2012-04-30 |
| CA2512559A1 (en) | 2004-08-12 |
| CN1744898A (zh) | 2006-03-08 |
| AU2004208644A1 (en) | 2004-08-12 |
| US20110256229A1 (en) | 2011-10-20 |
| DE602004001209T2 (de) | 2007-04-26 |
| NO20053277L (no) | 2005-07-15 |
| JP2006516616A (ja) | 2006-07-06 |
| CN100581586C (zh) | 2010-01-20 |
| AU2004208644B2 (en) | 2009-07-23 |
| DK1587514T3 (da) | 2006-10-16 |
| US20060216352A1 (en) | 2006-09-28 |
| PL378051A1 (pl) | 2006-02-20 |
| SI1587514T1 (sl) | 2006-10-31 |
| CY1106154T1 (el) | 2011-06-08 |
| KR20050096950A (ko) | 2005-10-06 |
| DE602004001209D1 (de) | 2011-01-05 |
| ES2270335T7 (es) | 2012-03-16 |
| PT1587514E (pt) | 2006-09-29 |
| WO2004067004A1 (en) | 2004-08-12 |
| DE602004001209T3 (de) | 2012-03-15 |
| NZ541167A (en) | 2008-07-31 |
| NO20053277D0 (no) | 2005-07-05 |
| EP1587514B1 (en) | 2006-06-14 |
| EP1587514A1 (en) | 2005-10-26 |
| MXPA05008140A (es) | 2005-09-30 |
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