NO319712B1 - Farmasoytiske formuleringer i hydroksypropylmetylcellulosekapsler - Google Patents
Farmasoytiske formuleringer i hydroksypropylmetylcellulosekapsler Download PDFInfo
- Publication number
- NO319712B1 NO319712B1 NO20013205A NO20013205A NO319712B1 NO 319712 B1 NO319712 B1 NO 319712B1 NO 20013205 A NO20013205 A NO 20013205A NO 20013205 A NO20013205 A NO 20013205A NO 319712 B1 NO319712 B1 NO 319712B1
- Authority
- NO
- Norway
- Prior art keywords
- cpt
- formulation according
- formulation
- capsule
- capsules
- Prior art date
Links
- 239000002775 capsule Substances 0.000 title claims description 46
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 title claims description 17
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 title claims description 17
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 title claims description 15
- 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 title claims description 15
- 239000008194 pharmaceutical composition Substances 0.000 title 1
- 238000009472 formulation Methods 0.000 claims description 43
- 239000000203 mixture Substances 0.000 claims description 43
- 239000007787 solid Substances 0.000 claims description 20
- 239000011159 matrix material Substances 0.000 claims description 16
- 206010028980 Neoplasm Diseases 0.000 claims description 9
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 9
- 239000002202 Polyethylene glycol Substances 0.000 claims description 8
- 229920001223 polyethylene glycol Polymers 0.000 claims description 8
- 229940127093 camptothecin Drugs 0.000 claims description 7
- 239000008203 oral pharmaceutical composition Substances 0.000 claims description 6
- 206010009944 Colon cancer Diseases 0.000 claims description 4
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 4
- 241000124008 Mammalia Species 0.000 claims description 4
- 125000005456 glyceride group Chemical group 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- FJHBVJOVLFPMQE-QFIPXVFZSA-N 7-Ethyl-10-Hydroxy-Camptothecin Chemical compound C1=C(O)C=C2C(CC)=C(CN3C(C4=C([C@@](C(=O)OC4)(O)CC)C=C33)=O)C3=NC2=C1 FJHBVJOVLFPMQE-QFIPXVFZSA-N 0.000 claims description 3
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical class C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 claims description 3
- 230000001613 neoplastic effect Effects 0.000 claims description 3
- MYQKIWCVEPUPIL-QFIPXVFZSA-N 7-ethylcamptothecin Chemical compound C1=CC=C2C(CC)=C(CN3C(C4=C([C@@](C(=O)OC4)(O)CC)C=C33)=O)C3=NC2=C1 MYQKIWCVEPUPIL-QFIPXVFZSA-N 0.000 claims description 2
- 206010027476 Metastases Diseases 0.000 claims description 2
- 201000010099 disease Diseases 0.000 claims description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 2
- 235000013305 food Nutrition 0.000 claims description 2
- 150000003904 phospholipids Chemical class 0.000 claims description 2
- 229920001983 poloxamer Polymers 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 239000004094 surface-active agent Substances 0.000 claims description 2
- 229960000303 topotecan Drugs 0.000 claims description 2
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 claims description 2
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 claims 4
- 230000002265 prevention Effects 0.000 claims 2
- 241001465754 Metazoa Species 0.000 claims 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims 1
- 229960000502 poloxamer Drugs 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- GURKHSYORGJETM-WAQYZQTGSA-N irinotecan hydrochloride (anhydrous) Chemical compound Cl.C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 GURKHSYORGJETM-WAQYZQTGSA-N 0.000 description 21
- 239000013543 active substance Substances 0.000 description 16
- 238000004090 dissolution Methods 0.000 description 16
- 229940079593 drug Drugs 0.000 description 10
- 239000003814 drug Substances 0.000 description 10
- 239000007903 gelatin capsule Substances 0.000 description 10
- 238000004519 manufacturing process Methods 0.000 description 9
- 102000057297 Pepsin A Human genes 0.000 description 8
- 108090000284 Pepsin A Proteins 0.000 description 8
- 238000004132 cross linking Methods 0.000 description 8
- 229940111202 pepsin Drugs 0.000 description 8
- 108010010803 Gelatin Proteins 0.000 description 7
- 229920000159 gelatin Polymers 0.000 description 7
- 239000008273 gelatin Substances 0.000 description 7
- 235000019322 gelatine Nutrition 0.000 description 7
- 235000011852 gelatine desserts Nutrition 0.000 description 7
- 238000003860 storage Methods 0.000 description 7
- 230000000694 effects Effects 0.000 description 6
- 238000009516 primary packaging Methods 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 101150073133 Cpt1a gene Proteins 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 230000032683 aging Effects 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 210000004051 gastric juice Anatomy 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 238000002144 chemical decomposition reaction Methods 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 229920002560 Polyethylene Glycol 3000 Polymers 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 3
- 229940041181 antineoplastic drug Drugs 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 102000038379 digestive enzymes Human genes 0.000 description 2
- 108091007734 digestive enzymes Proteins 0.000 description 2
- 239000012738 dissolution medium Substances 0.000 description 2
- 238000007922 dissolution test Methods 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 239000006186 oral dosage form Substances 0.000 description 2
- 229920002523 polyethylene Glycol 1000 Polymers 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 2
- 229940123780 DNA topoisomerase I inhibitor Drugs 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 239000000365 Topoisomerase I Inhibitor Substances 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 238000013475 authorization Methods 0.000 description 1
- 208000035269 cancer or benign tumor Diseases 0.000 description 1
- 239000007963 capsule composition Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229960004279 formaldehyde Drugs 0.000 description 1
- 235000019256 formaldehyde Nutrition 0.000 description 1
- 239000001087 glyceryl triacetate Substances 0.000 description 1
- 235000013773 glyceryl triacetate Nutrition 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 239000012943 hotmelt Substances 0.000 description 1
- -1 indolizino[1,2-b] quinolin-9-yl Chemical group 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229950010538 irinotecan hydrochloride trihydrate Drugs 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 239000011344 liquid material Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920000151 polyglycol Polymers 0.000 description 1
- 239000010695 polyglycol Substances 0.000 description 1
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229940068965 polysorbates Drugs 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 239000007962 solid dispersion Substances 0.000 description 1
- 239000006104 solid solution Substances 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229920001169 thermoplastic Polymers 0.000 description 1
- 239000004416 thermosoftening plastic Substances 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- 150000004684 trihydrates Chemical class 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—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
- 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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
-
- 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
- A61K9/4816—Wall or shell material
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9918885.6A GB9918885D0 (en) | 1999-08-10 | 1999-08-10 | Pharmaceutical formulations in hydroxypropymethycellulose capsules |
| PCT/EP2000/006590 WO2001010443A1 (en) | 1999-08-10 | 2000-07-11 | Pharmaceutical formulations in hydroxypropylmethylcellulose capsules |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO20013205L NO20013205L (no) | 2001-06-26 |
| NO20013205D0 NO20013205D0 (no) | 2001-06-26 |
| NO319712B1 true NO319712B1 (no) | 2005-09-05 |
Family
ID=10858930
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20013205A NO319712B1 (no) | 1999-08-10 | 2001-06-26 | Farmasoytiske formuleringer i hydroksypropylmetylcellulosekapsler |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US6569452B1 (hu) |
| EP (1) | EP1126851B1 (hu) |
| CN (1) | CN1245976C (hu) |
| AR (1) | AR025060A1 (hu) |
| AT (1) | ATE262905T1 (hu) |
| AU (1) | AU6158200A (hu) |
| CA (1) | CA2354039C (hu) |
| CO (1) | CO5200854A1 (hu) |
| CZ (1) | CZ293749B6 (hu) |
| DE (1) | DE60009442D1 (hu) |
| EA (1) | EA200100568A1 (hu) |
| GB (1) | GB9918885D0 (hu) |
| HK (1) | HK1040930B (hu) |
| HU (1) | HUP0104476A3 (hu) |
| IL (2) | IL143502A0 (hu) |
| NO (1) | NO319712B1 (hu) |
| PE (1) | PE20010407A1 (hu) |
| WO (1) | WO2001010443A1 (hu) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9925127D0 (en) * | 1999-10-22 | 1999-12-22 | Pharmacia & Upjohn Spa | Oral formulations for anti-tumor compounds |
| CN1316970C (zh) * | 2002-11-14 | 2007-05-23 | 武汉华中科大纳米药业有限公司 | 一种羟喜树碱固体分散物及其制剂 |
| JP2005183361A (ja) * | 2003-10-03 | 2005-07-07 | Ngk Insulators Ltd | 電子放出素子、電子放出装置、ディスプレイ及び光源 |
| US20050208146A1 (en) * | 2003-10-30 | 2005-09-22 | Pfizer Inc | Novel dosage and administration method for oral camptosar |
| GT200500310A (es) | 2004-11-19 | 2006-06-19 | Compuestos organicos | |
| SA06270147B1 (ar) | 2005-06-09 | 2009-12-22 | نوفارتيس ايه جي | عملية لتخليق 5-(مثيل–1h–إيميدازول–1-يل )–3-(ثلاثي فلـورو مثيل)–بنزامـين |
| WO2007033522A1 (fr) * | 2005-09-21 | 2007-03-29 | Shenzhen Tys R & D Co., Ltd. | Formulation de gélule contenant de la moxifloxacine et son procédé de préparation |
| GB0526419D0 (en) * | 2005-12-23 | 2006-02-08 | Cyclacel Ltd | Formulation |
| US20100008998A1 (en) * | 2006-09-26 | 2010-01-14 | Samyang Corporation | Submicron nanoparticle of poorly water soluble camptothecin derivatives and process for preparation thereof |
| JP2014517046A (ja) * | 2011-06-24 | 2014-07-17 | アセンダ ファーマ インコーポレイテッド | エステルプロドラッグの吸収を改善するための方法及び改善された医薬組成物 |
| CN103110605A (zh) * | 2011-11-17 | 2013-05-22 | 天士力制药集团股份有限公司 | 一种热熔胶囊制剂及其制备方法 |
| KR102537085B1 (ko) * | 2014-01-17 | 2023-05-25 | 옹코랄 파르마 에이피에스 | 암의 치료를 위한 이리노테칸의 고형 경구 투여형 |
| CN105287427B (zh) * | 2015-10-20 | 2017-04-19 | 沈阳红旗制药有限公司 | 一种利福平半固体胶囊及其制备方法 |
| KR102066402B1 (ko) * | 2017-12-22 | 2020-01-15 | 대화제약 주식회사 | 이리노테칸 또는 그의 약제학적으로 허용가능한 염을 포함하는 경구투여용 약제학적 조성물 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4678516A (en) * | 1984-10-09 | 1987-07-07 | The Dow Chemical Company | Sustained release dosage form based on highly plasticized cellulose ether gels |
| US5597829A (en) | 1994-05-09 | 1997-01-28 | Bionumerik Pharmaceuticals, Inc. | Lactone stable formulation of camptothecin and methods for uses thereof |
| EP0758237B1 (en) | 1994-04-28 | 2003-08-27 | Bionumerik Pharmaceuticals, Inc. | Lactone stable formulation of camptothecin or 7-ethyl camptothecin in dimethylisosorbide or dimethylacetamide |
| US5756123A (en) * | 1994-12-01 | 1998-05-26 | Japan Elanco Co., Ltd. | Capsule shell |
| US5726181A (en) * | 1995-06-05 | 1998-03-10 | Bionumerik Pharmaceuticals, Inc. | Formulations and compositions of poorly water soluble camptothecin derivatives |
| CN1088584C (zh) | 1996-08-02 | 2002-08-07 | 久光制药株式会社 | 口服制剂用胶囊及口服胶囊制剂 |
| AR013261A1 (es) | 1997-08-01 | 2000-12-13 | Smithkline Beecham Corp | Formulaciones farmaceuticas para analogos de camptotecina en capsula de gelatina |
-
1999
- 1999-08-10 GB GBGB9918885.6A patent/GB9918885D0/en not_active Ceased
-
2000
- 2000-07-11 AU AU61582/00A patent/AU6158200A/en not_active Abandoned
- 2000-07-11 AT AT00947971T patent/ATE262905T1/de not_active IP Right Cessation
- 2000-07-11 IL IL14350200A patent/IL143502A0/xx active IP Right Grant
- 2000-07-11 EA EA200100568A patent/EA200100568A1/ru unknown
- 2000-07-11 CA CA002354039A patent/CA2354039C/en not_active Expired - Fee Related
- 2000-07-11 CN CNB008021422A patent/CN1245976C/zh not_active Expired - Fee Related
- 2000-07-11 WO PCT/EP2000/006590 patent/WO2001010443A1/en active IP Right Grant
- 2000-07-11 HU HU0104476A patent/HUP0104476A3/hu unknown
- 2000-07-11 DE DE60009442T patent/DE60009442D1/de not_active Expired - Lifetime
- 2000-07-11 CZ CZ20012089A patent/CZ293749B6/cs not_active IP Right Cessation
- 2000-07-11 US US09/857,188 patent/US6569452B1/en not_active Expired - Fee Related
- 2000-07-11 EP EP00947971A patent/EP1126851B1/en not_active Expired - Lifetime
- 2000-08-07 AR ARP000104064A patent/AR025060A1/es unknown
- 2000-08-07 PE PE2000000795A patent/PE20010407A1/es not_active Application Discontinuation
- 2000-08-08 CO CO00059172A patent/CO5200854A1/es not_active Application Discontinuation
-
2001
- 2001-05-31 IL IL143502A patent/IL143502A/en not_active IP Right Cessation
- 2001-06-26 NO NO20013205A patent/NO319712B1/no not_active IP Right Cessation
-
2002
- 2002-04-11 HK HK02102740.7A patent/HK1040930B/zh not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| NO20013205L (no) | 2001-06-26 |
| CN1327387A (zh) | 2001-12-19 |
| HUP0104476A3 (en) | 2004-05-28 |
| CN1245976C (zh) | 2006-03-22 |
| CA2354039C (en) | 2008-09-23 |
| HK1040930B (zh) | 2006-10-27 |
| NO20013205D0 (no) | 2001-06-26 |
| HUP0104476A2 (hu) | 2002-03-28 |
| DE60009442D1 (de) | 2004-05-06 |
| EP1126851B1 (en) | 2004-03-31 |
| EA200100568A1 (ru) | 2001-10-22 |
| AR025060A1 (es) | 2002-11-06 |
| CA2354039A1 (en) | 2001-02-15 |
| CZ293749B6 (cs) | 2004-07-14 |
| GB9918885D0 (en) | 1999-10-13 |
| WO2001010443A1 (en) | 2001-02-15 |
| US6569452B1 (en) | 2003-05-27 |
| EP1126851A1 (en) | 2001-08-29 |
| PE20010407A1 (es) | 2001-03-28 |
| IL143502A0 (en) | 2002-04-21 |
| CZ20012089A3 (cs) | 2001-10-17 |
| HK1040930A1 (en) | 2002-06-28 |
| ATE262905T1 (de) | 2004-04-15 |
| AU6158200A (en) | 2001-03-05 |
| CO5200854A1 (es) | 2002-09-27 |
| IL143502A (en) | 2006-12-10 |
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