DE60117873D1 - Verfahren zur herstellung von submikropartikel-suspensionen pharmazeutischer substanzen - Google Patents
Verfahren zur herstellung von submikropartikel-suspensionen pharmazeutischer substanzenInfo
- Publication number
- DE60117873D1 DE60117873D1 DE60117873T DE60117873T DE60117873D1 DE 60117873 D1 DE60117873 D1 DE 60117873D1 DE 60117873 T DE60117873 T DE 60117873T DE 60117873 T DE60117873 T DE 60117873T DE 60117873 D1 DE60117873 D1 DE 60117873D1
- Authority
- DE
- Germany
- Prior art keywords
- submicroparticle
- suspensions
- producing
- pharmaceutical substances
- solvent
- 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.)
- Expired - Lifetime
Links
- 239000000725 suspension Substances 0.000 title abstract 3
- 238000004519 manufacturing process Methods 0.000 title 1
- 239000000126 substance Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 abstract 3
- 238000000034 method Methods 0.000 abstract 3
- 239000002904 solvent Substances 0.000 abstract 3
- 238000010899 nucleation Methods 0.000 abstract 2
- 239000003960 organic solvent Substances 0.000 abstract 2
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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- 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
- A61K9/10—Dispersions; Emulsions
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
-
- 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
- A61K9/14—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
- A61K9/1682—Processes
- A61K9/1688—Processes resulting in pure drug agglomerate optionally containing up to 5% of excipient
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Communicable Diseases (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Oncology (AREA)
- Dispersion Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Silicates, Zeolites, And Molecular Sieves (AREA)
- Physical Or Chemical Processes And Apparatus (AREA)
Applications Claiming Priority (15)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US874637 | 1986-06-16 | ||
US874499 | 1986-06-16 | ||
US35821 | 1998-03-06 | ||
US25816000P | 2000-12-22 | 2000-12-22 | |
US258160P | 2000-12-22 | ||
US09/874,799 US6607784B2 (en) | 2000-12-22 | 2001-06-05 | Microprecipitation method for preparing submicron suspensions |
US874799 | 2001-06-05 | ||
US09/874,637 US6869617B2 (en) | 2000-12-22 | 2001-06-05 | Microprecipitation method for preparing submicron suspensions |
US09/874,499 US7037528B2 (en) | 2000-12-22 | 2001-06-05 | Microprecipitation method for preparing submicron suspensions |
US953979 | 2001-09-17 | ||
US09/953,979 US6951656B2 (en) | 2000-12-22 | 2001-09-17 | Microprecipitation method for preparing submicron suspensions |
US10/035,821 US6977085B2 (en) | 2000-12-22 | 2001-10-19 | Method for preparing submicron suspensions with polymorph control |
US10/021,692 US6884436B2 (en) | 2000-12-22 | 2001-12-12 | Method for preparing submicron particle suspensions |
US21692 | 2001-12-12 | ||
PCT/US2001/049737 WO2002055059A2 (en) | 2000-12-22 | 2001-12-20 | Method for preparing submicron particle suspensions |
Publications (2)
Publication Number | Publication Date |
---|---|
DE60117873D1 true DE60117873D1 (de) | 2006-05-04 |
DE60117873T2 DE60117873T2 (de) | 2006-08-24 |
Family
ID=27567644
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DE60117873T Expired - Lifetime DE60117873T2 (de) | 2000-12-22 | 2001-12-20 | Verfahren zur herstellung von submikropartikel-suspensionen pharmazeutischer substanzen |
Country Status (16)
Country | Link |
---|---|
EP (2) | EP1642571A3 (de) |
JP (1) | JP4376518B2 (de) |
CN (1) | CN100512798C (de) |
AT (1) | ATE319432T1 (de) |
AU (2) | AU2002249836B2 (de) |
BR (1) | BR0116377A (de) |
CA (1) | CA2431705C (de) |
DE (1) | DE60117873T2 (de) |
DK (1) | DK1347747T3 (de) |
ES (1) | ES2260337T3 (de) |
HU (1) | HUP0501030A3 (de) |
IL (1) | IL156310A0 (de) |
MX (1) | MXPA03005496A (de) |
NO (1) | NO20032860L (de) |
NZ (1) | NZ526608A (de) |
WO (1) | WO2002055059A2 (de) |
Families Citing this family (44)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8067032B2 (en) * | 2000-12-22 | 2011-11-29 | Baxter International Inc. | Method for preparing submicron particles of antineoplastic agents |
US9700866B2 (en) * | 2000-12-22 | 2017-07-11 | Baxter International Inc. | Surfactant systems for delivery of organic compounds |
US20030072807A1 (en) * | 2000-12-22 | 2003-04-17 | Wong Joseph Chung-Tak | Solid particulate antifungal compositions for pharmaceutical use |
US20040022862A1 (en) * | 2000-12-22 | 2004-02-05 | Kipp James E. | Method for preparing small particles |
US20050048126A1 (en) | 2000-12-22 | 2005-03-03 | Barrett Rabinow | Formulation to render an antimicrobial drug potent against organisms normally considered to be resistant to the drug |
MXPA04002446A (es) | 2001-09-26 | 2004-07-23 | Baxter Int | Preparacion de nanoparticulas de tamano de submicras mediante dispersion y remocion de la fase liquida o solvente. |
US20060003012A9 (en) | 2001-09-26 | 2006-01-05 | Sean Brynjelsen | Preparation of submicron solid particle suspensions by sonication of multiphase systems |
US7112340B2 (en) * | 2001-10-19 | 2006-09-26 | Baxter International Inc. | Compositions of and method for preparing stable particles in a frozen aqueous matrix |
GB0216700D0 (en) * | 2002-07-18 | 2002-08-28 | Astrazeneca Ab | Process |
US20040028747A1 (en) * | 2002-08-06 | 2004-02-12 | Tucker Christopher J. | Crystalline drug particles prepared using a controlled precipitation process |
GB0302673D0 (en) | 2003-02-06 | 2003-03-12 | Astrazeneca Ab | Pharmaceutical formulations |
US7511079B2 (en) * | 2003-03-24 | 2009-03-31 | Baxter International Inc. | Methods and apparatuses for the comminution and stabilization of small particles |
WO2004096180A1 (en) * | 2003-04-29 | 2004-11-11 | Baxter International Inc. | Formulation to render an antimicrobial drug potent against organisms normally considered to be resistant to the drug |
US8986736B2 (en) | 2003-06-24 | 2015-03-24 | Baxter International Inc. | Method for delivering particulate drugs to tissues |
AU2004249172A1 (en) | 2003-06-24 | 2004-12-29 | Baxter International Inc. | Specific delivery of drugs to the brain |
MXPA06000720A (es) * | 2003-07-18 | 2006-08-23 | Baxter Int | Metodos para fabricacion, usos y composiciones de particulas esfericas pequenas preparadas por separacion de fase controlada. |
CA2534471A1 (en) * | 2003-08-06 | 2005-02-17 | Eisai Co., Ltd. | Method and apparatus for producing ultrafine drug particles |
GB0327390D0 (en) * | 2003-11-25 | 2003-12-31 | Pfizer Ltd | Pharmaceutical formulations |
EP1727520A2 (de) * | 2003-12-09 | 2006-12-06 | Medcrystalforms, Llc | Verfahren zur herstellung von mischphasen-kokristallen mit wirkstoffen |
EP1713443A2 (de) * | 2004-01-29 | 2006-10-25 | Baxter International Inc. | Nanosuspensionen von antiretroviralen mitteln für die verbesserte abgabe an das zentrale nervensystem |
EP1731138B1 (de) * | 2004-03-31 | 2016-03-23 | Toyama Chemical Co., Ltd. | Feine dispersion eines schwerlöslichen arzneimittels und herstellungsverfahren dafür |
MXPA06011171A (es) | 2004-06-15 | 2007-01-25 | Baxter Int | Aplicacion ex-vivo de agentes terapeuticos microparticulados solidos. |
DE102004031538A1 (de) * | 2004-06-29 | 2006-02-09 | Baxter International Inc., Deerfield | Pharmazeutische Darreichungsform zur oralen Verabreichung eines schwerlöslichen Wirkstoffs, Verfahren zu deren Herstellung und Kit |
US20060159766A1 (en) * | 2004-12-15 | 2006-07-20 | Elan Pharma International Limited | Nanoparticulate tacrolimus formulations |
WO2006101972A2 (en) * | 2005-03-17 | 2006-09-28 | Elan Pharma International Limited | Injectable compositions of nanoparticulate immunosuppressive compounds |
DE102005053862A1 (de) * | 2005-11-04 | 2007-05-10 | Pharmasol Gmbh | Verfahren und Vorrichtung zur Herstellung hochfeiner Partikel sowie zur Beschichtung solcher Partikel |
US20070134341A1 (en) * | 2005-11-15 | 2007-06-14 | Kipp James E | Compositions of lipoxygenase inhibitors |
ES2447465T3 (es) | 2008-03-05 | 2014-03-12 | Baxter International Inc. | Partículas de superficie modificada y métodos para la administración dirigida de fármacos |
DE102009008478A1 (de) | 2009-02-11 | 2010-08-19 | PHAST Gesellschaft für pharmazeutische Qualitätsstandards mbH | Vorrichtung und Verfahren zur Herstellung pharmazeutisch hochfeiner Partikel sowie zur Beschichtung solcher Partikel in Mikroreaktoren |
US10952965B2 (en) | 2009-05-15 | 2021-03-23 | Baxter International Inc. | Compositions and methods for drug delivery |
MX2012010868A (es) | 2010-03-22 | 2013-02-26 | Mjr Pharmjet Gmbh | Procedimiento y dispositivo para la preparacion de micro o nanoparticulas. |
CN102384973B (zh) * | 2011-08-10 | 2014-09-10 | 华南理工大学 | 快速定量检测羟甲基糠醛的免疫层析试纸条及其制备方法 |
CN102268103B (zh) * | 2011-09-02 | 2013-06-05 | 中国海洋大学 | 一种壳聚糖醋酸盐的制备方法 |
US9248139B2 (en) * | 2011-12-21 | 2016-02-02 | Bristol-Myers Squibb Company | Co-processing method and formulations for HIV attachment inhibitor prodrug compound and excipients |
CN103212079A (zh) * | 2013-04-26 | 2013-07-24 | 陆媛 | 一种预防和/或治疗感冒的含服药物组合物及其应用 |
CN104905262B (zh) * | 2015-05-29 | 2017-12-22 | 湖北省农业科学院农产品加工与核农技术研究所 | 一种制备虫草灵芝复合制剂的方法 |
KR101725508B1 (ko) * | 2015-07-31 | 2017-04-11 | 국방과학연구소 | 헥사나이트로스틸벤 입자의 제조 방법과 그 장치 |
CN105969316B (zh) * | 2016-06-03 | 2020-11-10 | 宁海德宝立新材料有限公司 | 一种用于热敷的相变储热复合材料 |
CA3030308C (en) | 2016-07-29 | 2022-04-05 | The Board Of Trustees Of Western Michigan University | Magnetic nanoparticle-based gyroscopic sensor |
CN108031142A (zh) * | 2017-12-13 | 2018-05-15 | 上海合全药物研发有限公司 | 一种简化的利用湿磨来制备大量微晶种的装置及方法 |
CN115349630A (zh) * | 2022-06-20 | 2022-11-18 | 海宁凤鸣叶绿素有限公司 | 水分散性叶黄素微囊粉的制备方法 |
WO2024136660A1 (en) * | 2022-12-22 | 2024-06-27 | Nanomi B.V. | Process for preparing stable nanoparticle and composition thereof |
WO2024153857A1 (en) | 2023-01-18 | 2024-07-25 | Nanoform Finland Oyj | A method for crystallization of active pharmaceutical ingredients |
CN116143803A (zh) * | 2023-01-29 | 2023-05-23 | 山东省分析测试中心 | 一种大颗粒头孢哌酮钠球形晶体的制备方法 |
Family Cites Families (17)
Publication number | Priority date | Publication date | Assignee | Title |
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CA1282405C (en) * | 1984-05-21 | 1991-04-02 | Michael R. Violante | Method for making uniformly sized particles from water-insoluble organic compounds |
US4826689A (en) * | 1984-05-21 | 1989-05-02 | University Of Rochester | Method for making uniformly sized particles from water-insoluble organic compounds |
US4606940A (en) * | 1984-12-21 | 1986-08-19 | The Ohio State University Research Foundation | Small particle formation and encapsulation |
FR2634397B2 (fr) * | 1986-12-31 | 1991-04-19 | Centre Nat Rech Scient | Procede de preparation de systemes colloidaux dispersibles d'une proteine sous forme de nanoparticules |
FR2608988B1 (fr) * | 1986-12-31 | 1991-01-11 | Centre Nat Rech Scient | Procede de preparation de systemes colloidaux dispersibles d'une substance, sous forme de nanoparticules |
IL86211A (en) * | 1987-05-04 | 1992-03-29 | Ciba Geigy Ag | Oral forms of administration for carbamazepine in the forms of stable aqueous suspension with delayed release and their preparation |
JP3282731B2 (ja) * | 1990-06-15 | 2002-05-20 | メルク エンド カムパニー インコーポレーテッド | 結晶の構造および大きさを改良する結晶化方法 |
US5145684A (en) * | 1991-01-25 | 1992-09-08 | Sterling Drug Inc. | Surface modified drug nanoparticles |
GB9413202D0 (en) * | 1994-06-30 | 1994-08-24 | Univ Bradford | Method and apparatus for the formation of particles |
SE9403846D0 (sv) * | 1994-11-09 | 1994-11-09 | Univ Ohio State Res Found | Small particle formation |
KR19990001564A (ko) * | 1997-06-16 | 1999-01-15 | 유충식 | 용해도를 개선한 아졸계 항진균제 및 이를 함유하는 제제 |
FI973804A (fi) * | 1997-09-26 | 1999-03-27 | Orion Yhtymae Oy | Levosimendaanin oraalisia koostumuksia |
WO1999033467A1 (en) * | 1997-12-31 | 1999-07-08 | Choongwae Pharma Corporation | Method and composition of an oral preparation of itraconazole |
EP1079808B1 (de) * | 1998-05-29 | 2004-02-11 | Skyepharma Canada Inc. | Gegen hitzeeinwirkung geschützte mikropartikel und verfahren zur terminalen dampfsterilisation derselben |
EP1104291B1 (de) * | 1998-07-17 | 2005-09-07 | Janssen Pharmaceutica N.V. | Granulat mit einem fungizid und einem polymer umhüllten kern |
DE60023465T2 (de) * | 1999-03-24 | 2006-07-20 | R.P. Scherer Technologies, Inc., Las Vegas | Pharmazeutische formulierungen mit verbesserter löslichkeit in wasser |
KR100331529B1 (ko) * | 1999-06-16 | 2002-04-06 | 민경윤 | 난용성 항진균제의 경구투여용 조성물 및 그의 제조 방법 |
-
2001
- 2001-12-20 BR BR0116377-9A patent/BR0116377A/pt not_active IP Right Cessation
- 2001-12-20 AU AU2002249836A patent/AU2002249836B2/en not_active Ceased
- 2001-12-20 EP EP05077486A patent/EP1642571A3/de not_active Withdrawn
- 2001-12-20 NZ NZ526608A patent/NZ526608A/en not_active IP Right Cessation
- 2001-12-20 DK DK01998077T patent/DK1347747T3/da active
- 2001-12-20 CA CA2431705A patent/CA2431705C/en not_active Expired - Fee Related
- 2001-12-20 JP JP2002555793A patent/JP4376518B2/ja not_active Expired - Fee Related
- 2001-12-20 CN CNB018211038A patent/CN100512798C/zh not_active Expired - Fee Related
- 2001-12-20 ES ES01998077T patent/ES2260337T3/es not_active Expired - Lifetime
- 2001-12-20 MX MXPA03005496A patent/MXPA03005496A/es active IP Right Grant
- 2001-12-20 HU HU0501030A patent/HUP0501030A3/hu unknown
- 2001-12-20 EP EP01998077A patent/EP1347747B1/de not_active Expired - Lifetime
- 2001-12-20 DE DE60117873T patent/DE60117873T2/de not_active Expired - Lifetime
- 2001-12-20 IL IL15631001A patent/IL156310A0/xx unknown
- 2001-12-20 WO PCT/US2001/049737 patent/WO2002055059A2/en active Application Filing
- 2001-12-20 AT AT01998077T patent/ATE319432T1/de active
-
2003
- 2003-06-20 NO NO20032860A patent/NO20032860L/no not_active Application Discontinuation
-
2006
- 2006-05-10 AU AU2006201943A patent/AU2006201943A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
EP1642571A3 (de) | 2007-06-27 |
CA2431705C (en) | 2010-10-05 |
AU2002249836B2 (en) | 2006-12-14 |
EP1347747B1 (de) | 2006-03-08 |
IL156310A0 (en) | 2004-01-04 |
JP2004538249A (ja) | 2004-12-24 |
BR0116377A (pt) | 2005-12-13 |
CN1505503A (zh) | 2004-06-16 |
NO20032860D0 (no) | 2003-06-20 |
CA2431705A1 (en) | 2002-07-18 |
DK1347747T3 (da) | 2006-04-10 |
DE60117873T2 (de) | 2006-08-24 |
CN100512798C (zh) | 2009-07-15 |
EP1642571A2 (de) | 2006-04-05 |
ATE319432T1 (de) | 2006-03-15 |
WO2002055059A3 (en) | 2002-09-06 |
AU2006201943A1 (en) | 2006-06-01 |
JP4376518B2 (ja) | 2009-12-02 |
NO20032860L (no) | 2003-08-21 |
NZ526608A (en) | 2006-06-30 |
EP1347747A2 (de) | 2003-10-01 |
HUP0501030A3 (en) | 2008-04-28 |
ES2260337T3 (es) | 2006-11-01 |
MXPA03005496A (es) | 2004-05-14 |
HUP0501030A2 (en) | 2007-02-28 |
WO2002055059A2 (en) | 2002-07-18 |
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