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AR011846A1 - Una composicion farmaceutica, y el procedimiento para prepararla - Google Patents

Una composicion farmaceutica, y el procedimiento para prepararla

Info

Publication number
AR011846A1
AR011846A1 ARP980100785A ARP980100785A AR011846A1 AR 011846 A1 AR011846 A1 AR 011846A1 AR P980100785 A ARP980100785 A AR P980100785A AR P980100785 A ARP980100785 A AR P980100785A AR 011846 A1 AR011846 A1 AR 011846A1
Authority
AR
Argentina
Prior art keywords
pharmaceutical composition
procedure
prepare
compound
unsurfactant
Prior art date
Application number
ARP980100785A
Other languages
English (en)
Original Assignee
Astellas Pharma Inc
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Astellas Pharma Inc filed Critical Astellas Pharma Inc
Publication of AR011846A1 publication Critical patent/AR011846A1/es

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0014Skin, i.e. galenical aspects of topical compositions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/407Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/4353Heterocyclic 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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/436Heterocyclic 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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00Drugs for genital or sexual disorders; Contraceptives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00Drugs for disorders of the muscular or neuromuscular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00Drugs for disorders of the senses
    • A61P27/02Ophthalmic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00Antiparasitic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • A61P37/06Immunosuppressants, e.g. drugs for graft rejection
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone

Landscapes

  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Diabetes (AREA)
  • Immunology (AREA)
  • Dermatology (AREA)
  • Neurology (AREA)
  • Urology & Nephrology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Endocrinology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Hematology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Neurosurgery (AREA)
  • Rheumatology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Reproductive Health (AREA)
  • Transplantation (AREA)
  • Pulmonology (AREA)
  • Pain & Pain Management (AREA)
  • Biomedical Technology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Vascular Medicine (AREA)
  • Emergency Medicine (AREA)

Abstract

Se proporciona una composicion farmacéutica que comprende un compuesto tricíclico (I) su sal aceptable farmacéuticamente, una substancia oleosa, unsurfactante, una substancia hidrofílica, agua, y opcionalmente un agente de control de pH,con estabilidad mejorada y/o un potencial de irritacion bajo.El compuesto tiene la formula (I): en la cual los sustituyentes variables tienen el significado dado en la descripcion. Se describe además elprocedimiento para preparar dichacomposicion farmacéutica.
ARP980100785A 1997-02-20 1998-02-20 Una composicion farmaceutica, y el procedimiento para prepararla AR011846A1 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP3617297 1997-02-20
JP25635797 1997-09-22

Publications (1)

Publication Number Publication Date
AR011846A1 true AR011846A1 (es) 2000-09-13

Family

ID=26375217

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP980100785A AR011846A1 (es) 1997-02-20 1998-02-20 Una composicion farmaceutica, y el procedimiento para prepararla

Country Status (20)

Country Link
US (1) US6387918B1 (es)
EP (1) EP0977565B1 (es)
JP (1) JP3396888B2 (es)
KR (1) KR100490357B1 (es)
CN (1) CN1178656C (es)
AR (1) AR011846A1 (es)
AT (1) ATE237325T1 (es)
AU (1) AU727337B2 (es)
BR (1) BR9807234B1 (es)
CA (1) CA2282345C (es)
DE (1) DE69813542T2 (es)
DK (1) DK0977565T3 (es)
EA (1) EA003580B1 (es)
ES (1) ES2193515T3 (es)
HU (1) HU226163B1 (es)
IL (1) IL131298A (es)
NO (1) NO325103B1 (es)
PT (1) PT977565E (es)
TW (1) TW450810B (es)
WO (1) WO1998036747A1 (es)

Families Citing this family (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2284248T3 (es) * 1998-04-27 2007-11-01 Astellas Pharma Inc. Formulacion farmaceutica en gel que comprende un compuesto triciclico (fk-506/tacrolimus).
GB9817064D0 (en) * 1998-08-05 1998-10-07 Fujisawa Pharmaceutical Co New use
US7063857B1 (en) 1999-04-30 2006-06-20 Sucampo Ag Use of macrolide compounds for the treatment of dry eye
US20030018044A1 (en) * 2000-02-18 2003-01-23 Peyman Gholam A. Treatment of ocular disease
AUPR529701A0 (en) * 2001-05-28 2001-06-21 Fujisawa Pharmaceutical Co., Ltd. Pharmaceutical composition
MXPA04005023A (es) 2001-11-29 2004-08-11 3M Innovative Properties Co Formulaciones farmaceuticas que comprenden un modificador de respuesta inmune.
JP2006511475A (ja) * 2002-09-18 2006-04-06 トラスティーズ オブ ザ ユニバーシティ オブ ペンシルベニア 脈絡膜新生血管症の抑制方法
PL1663217T3 (pl) 2003-08-29 2010-12-31 Lifecycle Pharma As Stałe dyspersje zawierające takrolimus
CN1859909B (zh) 2003-08-29 2011-04-06 生命周期药物公司 含有他克莫司的固态分散体
WO2005027906A1 (en) * 2003-09-18 2005-03-31 Macusight, Inc. Transscleral delivery
KR20070104931A (ko) * 2005-02-09 2007-10-29 마커사이트, 인코포레이티드 안구 치료용 제제
US8663639B2 (en) * 2005-02-09 2014-03-04 Santen Pharmaceutical Co., Ltd. Formulations for treating ocular diseases and conditions
KR20140093764A (ko) 2006-02-09 2014-07-28 산텐 세이야꾸 가부시키가이샤 안정한 제제와 그 제조 및 사용 방법
US7672006B2 (en) * 2006-02-22 2010-03-02 Xerox Corporation Multi-marking engine printing platform
PL2001466T3 (pl) * 2006-03-23 2016-06-30 Santen Pharmaceutical Co Ltd Rapamycyna w małej dawce do leczenia chorób związanych z przepuszczalnością naczyń
AU2007238896A1 (en) * 2006-04-10 2007-10-25 Merck Sharp & Dohme Corp. CGRP antagonist salt
US20080265343A1 (en) * 2007-04-26 2008-10-30 International Business Machines Corporation Field effect transistor with inverted t shaped gate electrode and methods for fabrication thereof
US12083103B2 (en) 2007-05-30 2024-09-10 Veloxis Pharmaceuticals, Inc. Tacrolimus for improved treatment of transplant patients
WO2008145143A1 (en) 2007-05-30 2008-12-04 Lifecycle Pharma A/S Once daily oral dosage form comprising tacrolimus
US12403095B2 (en) 2008-05-30 2025-09-02 Veloxis Pharmaceuticals, Inc. Stabilized tacrolimus composition
WO2010041684A1 (ja) 2008-10-08 2010-04-15 高田製薬株式会社 タクロリムス外用剤
TWI510238B (zh) * 2010-02-17 2015-12-01 Lifecycle Pharma As 穩定化他克莫司(tacrolimus)組合物
JP5674786B2 (ja) * 2010-07-23 2015-02-25 マルホ株式会社 タクロリムスを含有する水中油型クリーム状組成物
WO2012011192A1 (ja) * 2010-07-23 2012-01-26 マルホ株式会社 タクロリムスを含有する水中油型クリーム状組成物
WO2013084995A1 (ja) * 2011-12-07 2013-06-13 久光製薬株式会社 貼付剤
WO2013111817A1 (ja) * 2012-01-25 2013-08-01 マルホ株式会社 タクロリムスを含有する水中油型クリーム状組成物
KR102706357B1 (ko) 2015-08-19 2024-09-11 비버스 인크. 제약 제제
JP6997222B2 (ja) 2017-06-23 2022-01-17 ザ プロクター アンド ギャンブル カンパニー 皮膚の外観を改善するための組成物及び方法
WO2019233722A1 (en) 2018-06-08 2019-12-12 Almirall, S.A. Pharmaceutical composition comprising tacrolimus
US11622963B2 (en) 2018-07-03 2023-04-11 The Procter & Gamble Company Method of treating a skin condition
US10959933B1 (en) 2020-06-01 2021-03-30 The Procter & Gamble Company Low pH skin care composition and methods of using the same
CN115843238B (zh) 2020-06-01 2025-06-10 宝洁公司 改善维生素b3化合物渗透到皮肤中的方法
CA3212370A1 (en) 2021-03-03 2022-09-09 Sana Biotechnology, Inc. Immunosuppressive therapies for use with cardiomyocyte cell therapies, and associated methods and compositions

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK0406791T3 (da) * 1989-07-05 1995-03-27 Fujisawa Pharmaceutical Co Vandigt flydende præparat til ekstern anvendelse
ES2099112T3 (es) * 1990-09-04 1997-05-16 Fujisawa Pharmaceutical Co Pomadas que contienen un compuesto triciclico.
IE65341B1 (en) * 1990-11-08 1995-10-18 Fujisawa Pharmaceutical Co Suspensions containing tricyclic compounds
JPH06183970A (ja) 1992-12-16 1994-07-05 Fujisawa Pharmaceut Co Ltd 医薬用組成物
JPH06345646A (ja) * 1993-06-08 1994-12-20 Fujisawa Pharmaceut Co Ltd ローション剤
PT786986E (pt) 1994-10-26 2002-07-31 Novartis Ag Formulacoes farmaceuticas

Also Published As

Publication number Publication date
ES2193515T3 (es) 2003-11-01
EP0977565B1 (en) 2003-04-16
JP3396888B2 (ja) 2003-04-14
EA003580B1 (ru) 2003-06-26
AU6228998A (en) 1998-09-09
EA199900749A1 (ru) 2000-04-24
PT977565E (pt) 2004-01-30
NO994003D0 (no) 1999-08-19
TW450810B (en) 2001-08-21
CN1252721A (zh) 2000-05-10
HU226163B1 (en) 2008-05-28
HK1027957A1 (en) 2001-02-02
DE69813542D1 (de) 2003-05-22
BR9807234B1 (pt) 2013-11-05
CN1178656C (zh) 2004-12-08
IL131298A (en) 2004-06-20
BR9807234A (pt) 2000-04-25
KR20000070824A (ko) 2000-11-25
IL131298A0 (en) 2001-01-28
US20020032212A1 (en) 2002-03-14
KR100490357B1 (ko) 2005-05-17
NO994003L (no) 1999-10-19
EP0977565A1 (en) 2000-02-09
DK0977565T3 (da) 2003-08-04
JP2000513739A (ja) 2000-10-17
US6387918B1 (en) 2002-05-14
ATE237325T1 (de) 2003-05-15
HUP0000979A1 (hu) 2000-10-28
NO325103B1 (no) 2008-02-04
AU727337B2 (en) 2000-12-07
CA2282345C (en) 2008-10-21
DE69813542T2 (de) 2003-11-20
CA2282345A1 (en) 1998-08-27
WO1998036747A1 (en) 1998-08-27
HUP0000979A3 (en) 2002-10-28

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