DE69631527T2 - Aminosterinverbindungen als inhibitoren der natrium/proton-pump, pharmazeutische methoden und präparaten davon - Google Patents

Aminosterinverbindungen als inhibitoren der natrium/proton-pump, pharmazeutische methoden und präparaten davon Download PDF

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Publication number
DE69631527T2
DE69631527T2 DE69631527T DE69631527T DE69631527T2 DE 69631527 T2 DE69631527 T2 DE 69631527T2 DE 69631527 T DE69631527 T DE 69631527T DE 69631527 T DE69631527 T DE 69631527T DE 69631527 T2 DE69631527 T2 DE 69631527T2
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DE
Germany
Prior art keywords
squalamine
cells
compound
nhe
growth
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
DE69631527T
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German (de)
English (en)
Other versions
DE69631527D1 (de
Inventor
Michael Zasloff
Ann Shinnar
William A. Kinney
Jon Williams
Meena N. Rao
Mark Anderson
Michael Mclane
Steven Jones
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Genaera Corp
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Genaera Corp
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
Priority claimed from US08/487,443 external-priority patent/US5847172A/en
Priority claimed from US08/483,059 external-priority patent/US5840740A/en
Priority claimed from US08/483,057 external-priority patent/US5795885A/en
Priority claimed from US08/476,855 external-priority patent/US5874597A/en
Priority claimed from US08/475,572 external-priority patent/US5840936A/en
Priority claimed from US08/479,457 external-priority patent/US5763430A/en
Priority claimed from US08/479,455 external-priority patent/US5994336A/en
Application filed by Genaera Corp filed Critical Genaera Corp
Publication of DE69631527D1 publication Critical patent/DE69631527D1/de
Application granted granted Critical
Publication of DE69631527T2 publication Critical patent/DE69631527T2/de
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • 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
    • 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
    • A61P31/04—Antibacterial agents
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
    • C07J41/0005—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring the nitrogen atom being directly linked to the cyclopenta(a)hydro phenanthrene skeleton
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5011—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing antineoplastic activity
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5044—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving specific cell types
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5044—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving specific cell types
    • G01N33/5047—Cells of the immune system
    • G01N33/505—Cells of the immune system involving T-cells
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5044—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving specific cell types
    • G01N33/5058—Neurological cells
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5044—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving specific cell types
    • G01N33/5061—Muscle cells
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5082—Supracellular entities, e.g. tissue, organisms
    • G01N33/5088—Supracellular entities, e.g. tissue, organisms of vertebrates
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00—Screening for compounds of potential therapeutic value

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Cell Biology (AREA)
  • Urology & Nephrology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Food Science & Technology (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Biochemistry (AREA)
  • Toxicology (AREA)
  • Analytical Chemistry (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (AREA)
  • Diabetes (AREA)
  • Obesity (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Child & Adolescent Psychology (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
DE69631527T 1995-06-07 1996-06-07 Aminosterinverbindungen als inhibitoren der natrium/proton-pump, pharmazeutische methoden und präparaten davon Expired - Lifetime DE69631527T2 (de)

Applications Claiming Priority (15)

Application Number Priority Date Filing Date Title
US08/483,059 US5840740A (en) 1995-06-07 1995-06-07 Aminosterol compounds and a method of treating infection using the aminosterol compounds
US487443 1995-06-07
US08/483,057 US5795885A (en) 1995-06-07 1995-06-07 Method of inhibiting profileration of cells by administering an aminosterol compound
US479455 1995-06-07
US08/476,855 US5874597A (en) 1995-06-07 1995-06-07 Certain aminosterol compounds and pharmaceutical compositions including these compounds
US08/475,572 US5840936A (en) 1995-06-07 1995-06-07 Aminosterol compounds useful as inhibitors of the sodium/proton exchanger (NHE)
US08/479,457 US5763430A (en) 1995-06-07 1995-06-07 Method of treating a viral infection by administering a steroid compound
US479457 1995-06-07
US08/487,443 US5847172A (en) 1995-06-07 1995-06-07 Certain aminosterol compounds and pharmaceutical compositions including these compounds
US483059 1995-06-07
US08/479,455 US5994336A (en) 1995-06-07 1995-06-07 Method of inhibiting proliferation of cells by administering an aminosterol compound
US483057 1995-06-07
US476855 1995-06-07
US475572 1995-06-07
PCT/US1996/010508 WO1996040728A2 (en) 1995-06-07 1996-06-07 Aminosterol compounds useful as inhibitors of the sodium/proton exchanger (nhe), pharmaceutical methods and compositions employing such inhibitors, and processes for evaluating the nhe-inhibitory efficacy of compounds

Publications (2)

Publication Number Publication Date
DE69631527D1 DE69631527D1 (de) 2004-03-18
DE69631527T2 true DE69631527T2 (de) 2004-09-23

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DE69631527T Expired - Lifetime DE69631527T2 (de) 1995-06-07 1996-06-07 Aminosterinverbindungen als inhibitoren der natrium/proton-pump, pharmazeutische methoden und präparaten davon

Country Status (10)

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EP (2) EP0832094B1 (enExample)
JP (2) JP4104164B2 (enExample)
AT (1) ATE259375T1 (enExample)
AU (1) AU723663C (enExample)
CA (1) CA2223910C (enExample)
DE (1) DE69631527T2 (enExample)
DK (1) DK0832094T3 (enExample)
ES (1) ES2216049T3 (enExample)
PT (1) PT832094E (enExample)
WO (1) WO1996040728A2 (enExample)

Families Citing this family (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5856535A (en) * 1994-08-18 1999-01-05 Magainin Pharmaceuticals, Inc. Aminosterol ester compounds
US6143738A (en) * 1995-06-07 2000-11-07 Magainin Pharmaceuticals, Inc. Therapeutic uses for an aminosterol compound
US5792635A (en) * 1995-06-07 1998-08-11 Magainin Pharmaceuticals, Inc. Method of inhibiting the sodium/proton exchanger NHE3 and method of inhibiting growth by administering squalamine
US6596712B2 (en) 1996-04-26 2003-07-22 Genaera Corporation Treatment of carcinomas using squalamine in combination with other anti-cancer agents or modalities
PT910382E (pt) * 1996-04-26 2003-10-31 Genaera Corp Esqualamina em combinacao com outros agentes anti-cancro para o tratamento de tumores
JP2002515035A (ja) * 1996-05-17 2002-05-21 ジェネーラ・コーポレーション アミノステロール化合物の治療学的使用
US7410959B1 (en) 2000-07-13 2008-08-12 Genaera Corporation Therapeutic uses for aminosterol compounds
WO1998019682A1 (en) * 1996-11-01 1998-05-14 Magainin Pharmaceuticals Inc. Certain aminosterol compounds and uses therefor
US6262283B1 (en) 1996-12-06 2001-07-17 Magainin Pharmaceuticals Inc. Stereoselective synthesis of 24-hydroxylated compounds useful for the preparation of aminosterols, vitamin D analogs, and other compounds
DE19737463A1 (de) * 1997-08-28 1999-03-04 Hoechst Marion Roussel De Gmbh Verwendung von Inhibitoren des Natrium-Wasserstoff-Austauschers zur Herstellung eines Arzneimittels zur Behandlung von Erkrankungen, die durch Protozoen verursacht werden
EP1274718B1 (en) 2000-04-12 2006-10-18 Genaera Corporation A process for the preparation of 7.alpha.-hydroxy 3-aminosubstituted sterols using intermediates with an unprotected 7.alpha.-hydroxy group
WO2006119211A2 (en) * 2005-05-02 2006-11-09 Genaera Corporation Methods and compositions for treating ocular disorders
US20080058300A1 (en) * 2006-04-21 2008-03-06 Mclane Michael Induction of weight loss and the selective inhibition of PTP1B
CA2985271A1 (en) * 2007-09-06 2009-03-12 Ohr Pharmaceutical, Inc. A method for treating diabetes
AU2009243749B2 (en) 2008-05-09 2013-11-21 Merck Patent Gmbh Pharmaceutical composition comprising rimeporide for treating diseases associated with insulin resistance and beta-cell dysfunction
PT2758060T (pt) * 2011-09-19 2018-01-24 ETH Zürich Moduladores de ror gama para o tratamento de complicações de diabetes ii
KR20150003798A (ko) * 2012-04-20 2015-01-09 오에이치알 파마서티컬, 인코포레이티드 Ptp1b 연관 질병의 치료용 아미노스테로이드
US11524015B2 (en) 2013-03-15 2022-12-13 Brigham Young University Methods for treating inflammation, autoimmune disorders and pain
BR112015023747B1 (pt) 2013-03-15 2023-04-18 Brigham Young University Uso de um composto antimicrobiano catiônico esteroide (csa) para a preparação de uma composição para tratar, reduzir, ou prevenir inflamação aguda ou crônica e/ou dor aguda ou crônica associada com uma doença ou um sintoma de doença
EP2781217A1 (en) * 2013-03-18 2014-09-24 ETH Zurich ROR gamma modulators
US10040817B2 (en) * 2013-10-03 2018-08-07 Enterin Laboratories, Inc. Methods and compositions for stimulation of the intestinal enteroendocrine system for treating diseases or conditions related to the same
US11690855B2 (en) 2013-10-17 2023-07-04 Brigham Young University Methods for treating lung infections and inflammation
US20150203527A1 (en) 2014-01-23 2015-07-23 Brigham Young University Cationic steroidal antimicrobials
US10441595B2 (en) * 2014-06-26 2019-10-15 Brigham Young University Methods for treating fungal infections
FR3033563B1 (fr) * 2015-03-12 2018-04-13 Virbac Composes analogues de la squalamine utiles comme agents antibacteriens
FR3055801B1 (fr) * 2016-09-15 2020-10-30 Virbac Derives esters de squalamine pour le traitement des infections
EP3678671A4 (en) * 2017-09-08 2022-12-07 Enterin, Inc. METHODS OF TREATMENT OF SLEEPING DISEASES, SLEEP DISORDERS AND RELATED SYMPTOMS USING AMINOSTEROL COMPOSITIONS
US11464789B2 (en) 2018-08-03 2022-10-11 Enterin, Inc. Aminosterol compositions and methods of using the same for treating schizophrenia
WO2020028810A1 (en) * 2018-08-03 2020-02-06 Enterin Laboratories Compositions and methods for treating brain-gut disorders
US12186328B2 (en) 2019-05-23 2025-01-07 Brigham Young University Use of CSA compounds to stimulate stem cells and hair growth
CA3149480A1 (en) * 2019-08-02 2021-02-11 Enterin, Inc. Human squalamine derivatives, related compositions comprising the same, and methods of using the same
MX2022001449A (es) * 2019-08-02 2022-04-06 Enterin Inc Compuestos de aminoesterol humano ent-03, composiciones relacionadas que comprenden los mismos y metodos para usar los mismos.
CN112782300B (zh) * 2020-12-25 2022-04-12 山东省食品药品检验研究院 一种胆烷酸的同分异构体及其检测方法和应用

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5192756A (en) * 1992-03-18 1993-03-09 The Children's Hospital Of Pennsylvania Aminosterol antibiotic
AU6392894A (en) * 1993-02-26 1994-09-14 Magainin Pharmaceuticals, Inc. Chemical synthesis of squalamine
CA2157594A1 (en) * 1993-03-10 1994-09-15 Leah L. Frye Steroid derivatives, pharmaceutical compositions containing them, and their use as antibiotics or disinfectants

Also Published As

Publication number Publication date
DE69631527D1 (de) 2004-03-18
AU723663C (en) 2001-11-01
CA2223910C (en) 2008-09-16
JP4104164B2 (ja) 2008-06-18
ES2216049T3 (es) 2004-10-16
AU723663B2 (en) 2000-08-31
WO1996040728A2 (en) 1996-12-19
WO1996040728A3 (en) 1997-03-27
PT832094E (pt) 2004-06-30
JP2002515019A (ja) 2002-05-21
ATE259375T1 (de) 2004-02-15
EP0832094B1 (en) 2004-02-11
JP2007314577A (ja) 2007-12-06
EP1420027A3 (en) 2012-01-04
EP0832094A2 (en) 1998-04-01
AU6334996A (en) 1996-12-30
DK0832094T3 (da) 2004-05-17
EP1420027A2 (en) 2004-05-19
CA2223910A1 (en) 1996-12-19

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