CA1328075C - Ocular hypotensive agents - Google Patents

Ocular hypotensive agents

Info

Publication number
CA1328075C
CA1328075C CA000577220A CA577220A CA1328075C CA 1328075 C CA1328075 C CA 1328075C CA 000577220 A CA000577220 A CA 000577220A CA 577220 A CA577220 A CA 577220A CA 1328075 C CA1328075 C CA 1328075C
Authority
CA
Canada
Prior art keywords
dihydro
keto
prostaglandins
ethyl
ester
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
Application number
CA000577220A
Other languages
English (en)
French (fr)
Inventor
Ryuzo Ueno
Ryuji Ueno
Tomio Oda
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
R Tech Ueno Ltd
Original Assignee
R Tech Ueno Ltd
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=26532381&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CA1328075(C) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by R Tech Ueno Ltd filed Critical R Tech Ueno Ltd
Application granted granted Critical
Publication of CA1328075C publication Critical patent/CA1328075C/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C405/00—Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins ; Analogues or derivatives thereof
    • 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
    • A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/06—Antiglaucoma agents or miotics
    • 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
    • A61P9/12—Antihypertensives

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Ophthalmology & Optometry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Materials For Medical Uses (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
CA000577220A 1987-09-18 1988-09-13 Ocular hypotensive agents Expired - Lifetime CA1328075C (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
JP23589087 1987-09-18
JP235890/1987 1987-09-18
JP334037/1987 1987-12-29
JP33403787 1987-12-29

Publications (1)

Publication Number Publication Date
CA1328075C true CA1328075C (en) 1994-03-29

Family

ID=26532381

Family Applications (1)

Application Number Title Priority Date Filing Date
CA000577220A Expired - Lifetime CA1328075C (en) 1987-09-18 1988-09-13 Ocular hypotensive agents

Country Status (11)

Country Link
US (1) US5001153A (2)
EP (2) EP0455264B1 (2)
JP (2) JPH02108A (2)
KR (1) KR930000051B1 (2)
AT (2) ATE82499T1 (2)
CA (1) CA1328075C (2)
DE (2) DE3850676T2 (2)
ES (1) ES2052735T3 (2)
GB (1) GB2209939B (2)
GR (1) GR3006319T3 (2)
NZ (1) NZ226197A (2)

Families Citing this family (112)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA1322749C (en) * 1987-01-28 1993-10-05 Ryuzo Ueno Prostaglandins of the d series, and tranquilizers and soporifics containing the same
US5236907A (en) * 1988-10-01 1993-08-17 R-Tech Ueno Ltd. Ocular hypotensive agents
US6420422B1 (en) 1987-09-18 2002-07-16 Sucampo Pharmaceuticals, Inc. Ocular hypotensive agents
JP2597629B2 (ja) 1988-02-26 1997-04-09 株式会社 上野製薬応用研究所 １３，１４−ジヒドロ−１５−ケトプロスタグランジン類の安定化
DE1300150T1 (de) 1988-09-06 2003-09-18 Pharmacia Ab, Stockholm Prostaglandin-Derivate zur Behandlung von Glaukom oder Augenüberdruck
US5296504A (en) * 1988-09-06 1994-03-22 Kabi Pharmacia Prostaglandin derivatives for the treatment of glaucoma or ocular hypertension
EP1300149A3 (en) * 1988-09-06 2003-05-14 Pharmacia Aktiebolag Prostaglandin derivatives for the treatment of glaucoma or ocular hypertension
US5321128A (en) * 1988-09-06 1994-06-14 Kabi Pharmacia Ab Prostaglandin derivatives for the treatment of glaucoma or ocular hypertension
US6187813B1 (en) 1990-04-10 2001-02-13 Pharmacia & Upjohn Aktiebolag Prostaglandin derivatives for the treatment of glaucoma or ocular hypertension
US5194429A (en) * 1988-10-01 1993-03-16 K.K. Ueno Seiyaku Oyo Kenkyujo Ocular hypotensive agents
DE68928551T2 (de) * 1988-10-01 1998-04-23 Ueno Seiyaku Oyo Kenkyujo Kk Oculare hypotensive Mittel
US5234954A (en) * 1989-07-27 1993-08-10 K.K. Ueno Seiyaku Oyo Kenkyujo Treatment of hyperlipidemia with 15-keto-prostaglandin compounds
EP0410652B1 (en) * 1989-07-27 1995-05-17 Kabushiki Kaisha Ueno Seiyaku Oyo Kenkyujo Use of 15-keto-prostanoic acid derivatives in the manufacture of a medicament for improvement of excretion of potassium ion
ATE121624T1 (de) * 1989-08-09 1995-05-15 Ueno Seiyaku Oyo Kenkyujo Kk Verwendung von prostansäurederivaten zur herstellung von arzneimitteln zur verbesserung der ausscheidung von nichtprotein in die därme.
CA2027814C (en) * 1989-10-20 1996-07-30 Ryuji Ueno Treatment of hepatobiliary disease with 15-keto-prostaglandin compounds
CA2030345C (en) * 1989-11-22 1998-12-08 Ryuji Ueno Use of 15-keto-prostaglandin compound for improvement of encephalic function
US5256696A (en) * 1989-11-22 1993-10-26 Kabushikikaisha Ueno Seiyaku Oyo Kenkyujo Treatment of cardiac dysfunction with 15-ketoprostaglandin compounds
US5254588A (en) * 1989-11-22 1993-10-19 Kabushikikaisha Ueno Seiyaku Oyo Kenkyujo Treatment of pulmonary dysfunction with 15-ketoprostaglandin compounds
CA2054738C (en) * 1990-03-08 2001-08-28 Morio Kishi 15-deoxyprostaglandin derivatives
TW224942B (2) * 1990-04-04 1994-06-11 Adka Ueno Kk
ATE174221T1 (de) * 1990-05-01 1998-12-15 R Tech Ueno Ltd Behandlung von pankreaskrankheit mit 15-keto- prostaglandin e-derivaten
US5175189A (en) * 1990-05-22 1992-12-29 K.K. Ueno Seiyaku Oyo Kenkyujo Treatment of ocular hypertension with a synergistic combination for ophthalmic use
CA2042934C (en) * 1990-05-22 2002-04-23 Ryuji Ueno Treatment of ocular hypertension with an ocular synergistic combination
DE69100171T2 (de) * 1990-05-22 1993-10-28 Ueno Seiyaku Oyo Kenkyujo Kk Synergistische Kombination zur ophthalmischen Verwendung.
ES2084771T3 (es) * 1990-05-22 1996-05-16 R Tech Ueno Ltd Tratamiento de la hipertension ocular con la ayuda de una combinacion sinergica.
US5208256A (en) * 1990-05-22 1993-05-04 R-Tech Ueno, Ltd. Treatment of ocular hypertension with a synergistic combination for ocular administration
CA2046069C (en) * 1990-07-10 2002-04-09 Ryuji Ueno Treatment of inflammatory diseases with 15-keto-prostaglandin compounds
US5270049A (en) * 1990-11-09 1993-12-14 Allergan, Inc. 2-decarboxyl-2-aminoalkyl-prostaglandins as ocular hypotensives
US5139491A (en) * 1990-12-06 1992-08-18 Allergan, Inc. 2-decarboxyl-2-alkoxyalkyl prostaglandins as ocular hypotensives
TW210287B (2) * 1991-03-01 1993-08-01 Kabushikaisha Ueno Seiyaku Oyo Kenkyujo
ES2093774T3 (es) * 1991-03-14 1997-01-01 R Tech Ueno Ltd Estimulacion de la curacion de heridas con un compuesto 15-cetoprostaglandina.
CA2065889C (en) * 1991-10-02 2002-08-27 Tetsuya Sugiyama Increasing the choroidal blood flow
EP0668076B1 (en) * 1992-08-26 2002-09-04 Sucampo AG Stabilization of a prostanoic acid compound
FR2707295A1 (fr) * 1993-06-07 1995-01-13 Rhone Poulenc Agrochimie Fongicides pyrazoles substitués en position 3 par un hétérocycle.
US6184250B1 (en) 1993-08-03 2001-02-06 Alcon Laboratories, Inc. Use of cloprostenol and fluprostenol analogues to treat glaucoma and ocular hypertension
US5510383A (en) * 1993-08-03 1996-04-23 Alcon Laboratories, Inc. Use of cloprostenol, fluprostenol and their salts and esters to treat glaucoma and ocular hypertension
US5387608A (en) * 1993-08-17 1995-02-07 Allergan, Inc. Cyclopentane(ene) heptanoic or cyclopentane(ene) heptenoic acid, 2-hydrocarbyl sulfonamidomethyl and derivatives thereof as therapeutic agents
JP2769294B2 (ja) * 1993-12-15 1998-06-25 アルコン ラボラトリーズ インコーポレイテッド 局所的眼薬組成物及びそのためのプロスタグランジン化合物
US5807892A (en) * 1994-09-30 1998-09-15 Alcon Laboratories, Inc. Use of certain prostaglandin analogues to treat glaucoma and ocular hypertension
TW420611B (en) * 1995-03-10 2001-02-01 R Tech Ueno Ltd Pharmaceutical composition containing prostanoic acid compounds for the treatment of optic nerve disorder
AU7680096A (en) * 1995-12-22 1997-07-17 Alcon Laboratories, Inc. Combinations of dp and fp type prostaglandins for lowering iop
CN1237157A (zh) 1996-11-12 1999-12-01 阿尔康实验室公司 作为眼压降低剂的前列腺素的顺式－△4类似物
US6680339B2 (en) 1996-11-12 2004-01-20 Alcon Manufacturing, Ltd. 15-fluoro prostaglandins as ocular hypotensives
DE69705421T2 (de) * 1996-11-12 2002-05-16 Alcon Laboratories, Inc. 15-fluoro-prostaglandine als augendrucksenkende mittel
ATE266397T1 (de) 1997-02-04 2004-05-15 Murray A Johnstone Verfahren zur förderung des haarwuchses und entwicklung des haarsystems
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US6770675B2 (en) 1997-03-17 2004-08-03 Novartis Ag Compositions and methods for reducing ocular hypertension
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US6156785A (en) * 1998-01-23 2000-12-05 Merck Sharp & Dohme B.V. Method for increasing oxygen tension in the optic nerve and retina
US6096783A (en) * 1998-12-15 2000-08-01 Alcon Laboratories, Inc. Cyclobutane prostaglandin analogues as ocular hypotensive agents
ATE289817T1 (de) * 1998-12-25 2005-03-15 Sucampo Ag Arzneimittelzusammenstellung zur behandlung des erhöhten augeninnendrucks oder des glaukom
SE9900672D0 (sv) 1999-02-25 1999-02-25 Synphora Ab Method and composition for prevention of scar formation in glaucoma filtration bleb and drainage fistula
JP4834224B2 (ja) 1999-03-05 2011-12-14 デューク ユニバーシティ Ｃ１６不飽和ｆｐ−選択的プロスタグランジン類縁体
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US6576663B2 (en) 1999-12-22 2003-06-10 Alcon, Inc. 6-Keto prostaglandin F1α and analogs for treating dry eye
US6548535B2 (en) * 2000-01-18 2003-04-15 Merck & Co., Inc. Method for treating ocular hypertension
AU771130B2 (en) * 2000-01-18 2004-03-11 Merck & Co., Inc. Ophthalmic compositions for treating ocular hypertension
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US6458836B1 (en) 2000-03-16 2002-10-01 Sucampo, A.G. Treatment of ocular hypertension and glaucoma
TWI284535B (en) * 2000-03-24 2007-08-01 Sucampo Ag Apoptosis inhibitor
US20020172693A1 (en) 2000-03-31 2002-11-21 Delong Michell Anthony Compositions and methods for treating hair loss using non-naturally occurring prostaglandins
US20020037914A1 (en) 2000-03-31 2002-03-28 Delong Mitchell Anthony Compositions and methods for treating hair loss using C16-C20 aromatic tetrahydro prostaglandins
US20020013294A1 (en) 2000-03-31 2002-01-31 Delong Mitchell Anthony Cosmetic and pharmaceutical compositions and methods using 2-decarboxy-2-phosphinico derivatives
US20020146439A1 (en) * 2000-03-31 2002-10-10 Delong Mitchell Anthony Compositions and methods for treating hair loss using oximyl and hydroxylamino prostaglandins
PE20020146A1 (es) * 2000-07-13 2002-03-31 Upjohn Co Formulacion oftalmica que comprende un inhibidor de ciclooxigenasa-2 (cox-2)
US20020035148A1 (en) * 2000-07-20 2002-03-21 Ryuji Ueno Treatment of ocular hypertension
US6414021B1 (en) * 2000-08-25 2002-07-02 Sucampo Ag Control of intraocular pressure during surgery
CA2422031C (en) * 2000-09-13 2011-11-15 Santen Pharmaceutical Co., Ltd. Ophthalmic solutions comprising difluoroprostaglandin f2 alpha
US6291522B1 (en) * 2000-09-27 2001-09-18 Allergan Sales, Inc. Cyclopentane heptan(ENE)oic acid, 2-thiocarbamoyloxy and 2-carbamoyloxy compounds as therapeutic agents
US20040254230A1 (en) * 2001-12-03 2004-12-16 Ogidigben Miller J. Method for treating ocular hypertension
US7351404B2 (en) 2002-02-04 2008-04-01 Allergan, Inc. Method of enhancing hair growth
US9216183B2 (en) 2002-02-04 2015-12-22 Allergan, Inc. Topical treatment for chemotherapy induced eyelash loss or hypotrichosis using prostamide F2 alpha agonists
US8758733B2 (en) 2002-02-04 2014-06-24 Allergan, Inc. Topical treatment for chemotherapy induced eyelash loss or hypotrichosis using prostamide F2 alpha agonists
EP1487438A4 (en) * 2002-03-15 2007-08-15 Merck & Co Inc COMPOSITIONS AND METHODS FOR TREATING GLUCKOM AND OKULAR HYPERTENSION
WO2003103664A1 (en) * 2002-06-06 2003-12-18 Merck Frosst Canada & Co. 1,5-disubstituted imidazolidin-2-one derivatives for use as ep4 receptor agonists in the treatment of eye and bone diseases
US20050256117A1 (en) * 2002-06-14 2005-11-17 Meng Hsin Chen Ophthalmic compositions for treating ocular hypertension
EP1515730A4 (en) * 2002-06-17 2005-07-20 Merck & Co Inc NEW MAXI-K CHANNEL BLOCKS, USE METHOD AND METHOD FOR THE PRODUCTION THEREOF
WO2003105724A2 (en) * 2002-06-17 2003-12-24 Merck & Co., Inc. Novel maxi-k channel blockers, methods of use and process for making the same
JP2005532361A (ja) * 2002-06-17 2005-10-27 メルク　エンド　カムパニー　インコーポレーテッド 高眼圧症の治療用の眼科用組成物
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AU2003258433A1 (en) * 2002-08-28 2004-03-19 Merck Frosst Canada Ltd Oxazolidin-2-one and thiazolidin-2-one derivatives for use as ep4 receptor agonists in the treatment of glaucoma
ATE546143T1 (de) * 2002-08-29 2012-03-15 Santen Pharmaceutical Co Ltd Mittel zur behandlung von glaukom mit einem rho- kinase-hemmer und prostaglandinen
US20060167081A1 (en) * 2002-10-25 2006-07-27 Xavier Billot Ep4 receptor agonists
US7972612B2 (en) 2002-11-18 2011-07-05 Santen Pharmaceutical Co., Ltd. Remedy for glaucoma comprising Rho kinase inhibitor and β-blocker
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WO2005011704A1 (ja) * 2003-07-31 2005-02-10 Santen Pharmaceutical Co., Ltd. プロスタグランジン含有製品
TWI495471B (zh) * 2003-08-12 2015-08-11 R Tech Ueno Ltd 促進毛髮生長之組成物及方法
DE602004023106D1 (de) 2003-11-07 2009-10-22 Senju Pharma Co Pharmazeutische zusammensetzung mit prostaglandin
CN102526064A (zh) * 2004-12-09 2012-07-04 参天制药株式会社 含有分子内具有氟原子的前列腺素的制品
WO2006068266A1 (ja) * 2004-12-24 2006-06-29 Santen Pharmaceutical Co., Ltd. プロスタグランジンＦ２ａ誘導体含有製品
EP1830793A1 (en) * 2004-12-29 2007-09-12 R-Tech Ueno, Ltd. Composition and method for scalp and hair treatment
KR20160120809A (ko) * 2005-03-04 2016-10-18 수캄포 아게 말초 혈관 질환 치료를 위한 방법 및 조성물
JP4648340B2 (ja) * 2006-02-07 2011-03-09 株式会社アールテック・ウエノ １５−ケトプロスタグランジンｅ誘導体の製造法
CN101400354B (zh) * 2006-03-13 2014-10-22 株式会社·R-技术上野 水性组合物
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US8722739B2 (en) 2008-10-29 2014-05-13 Novaer Holdings, Inc. Amino acid salts of prostaglandins
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US20100204335A1 (en) * 2008-12-01 2010-08-12 Allergan, Inc. Kit and composition for eyelash growth
US20110293549A1 (en) 2009-02-03 2011-12-01 Athena Cosmetics, Inc. Composition, method and kit for enhancing hair
US8609729B2 (en) 2009-04-15 2013-12-17 Sucampo Ag Method for treating macular degeneration
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CN103338772A (zh) 2011-02-04 2013-10-02 兴和株式会社 用于预防或治疗青光眼的药物疗法
TW201247206A (en) 2011-04-07 2012-12-01 Sucampo Ag Method for treating asthenopia
US8592483B2 (en) * 2011-08-05 2013-11-26 Sucampo Ag Method for treating schizophrenia
AR092821A1 (es) 2012-04-20 2015-05-06 Sucampo Ag Conjugado de derivado de acido graso-polimero
EA034839B1 (ru) 2014-10-20 2020-03-26 Сентисс Фарма Прайвет Лимитед Офтальмологический раствор

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1476661A (en) * 1974-05-13 1977-06-16 American Cyanamid Co Prostaglandins
US4599353A (en) * 1982-05-03 1986-07-08 The Trustees Of Columbia University In The City Of New York Use of eicosanoids and their derivatives for treatment of ocular hypertension and glaucoma
DE3785602T2 (de) * 1986-03-13 1993-09-02 Univ Columbia Verwendung von a-, b- und c-prostaglandinen und deren derivaten zur behandlung von augen-hypertension und glaukom.
US4824857A (en) * 1986-05-16 1989-04-25 Yasumasa Goh Use of prostaglandin D2 -active substances
CA1322749C (en) * 1987-01-28 1993-10-05 Ryuzo Ueno Prostaglandins of the d series, and tranquilizers and soporifics containing the same
CA1323364C (en) * 1987-01-28 1993-10-19 Ryuzo Ueno Prostaglandins e and anti ulcer agents containing same
CA1324129C (en) * 1987-04-30 1993-11-09 Ryuzo Ueno Prostaglandins of the f series
DE3869471D1 (de) * 1987-05-15 1992-04-30 Ueno Seiyaku Oyo Kenkyujo Kk Fiebersteigende zusammensetzung.
JPS6453101A (en) * 1987-05-25 1989-03-01 Kurashiki Boseki Kk Equal tilt angle interference type film thickness gauge
JP2597629B2 (ja) * 1988-02-26 1997-04-09 株式会社 上野製薬応用研究所 １３，１４−ジヒドロ−１５−ケトプロスタグランジン類の安定化

Also Published As

Publication number Publication date
EP0455264B1 (en) 1994-07-13
ES2052735T3 (es) 1994-07-16
EP0308135A2 (en) 1989-03-22
GB2209939B (en) 1992-01-02
JP2592204B2 (ja) 1997-03-19
AU600168B2 (en) 1990-08-02
GB8821104D0 (en) 1988-10-05
JPH02108A (ja) 1990-01-05
DE3850676D1 (de) 1994-08-18
EP0455264A3 (en) 1991-11-27
KR930000051B1 (ko) 1993-01-06
EP0455264A2 (en) 1991-11-06
DE3876050T2 (de) 1993-03-25
US5001153A (en) 1991-03-19
GR3006319T3 (2) 1993-06-21
ATE82499T1 (de) 1992-12-15
AU2231388A (en) 1989-03-23
DE3876050D1 (de) 1992-12-24
NZ226197A (en) 1992-02-25
GB2209939A (en) 1989-06-01
JPH0680571A (ja) 1994-03-22
DE3850676T2 (de) 1994-11-03
KR890004707A (ko) 1989-05-09
JPH0571567B2 (2) 1993-10-07
EP0308135B1 (en) 1992-11-19
EP0308135A3 (en) 1989-06-14
ATE108330T1 (de) 1994-07-15

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