WO2001054771A3 - Method for using potassium channel agonists for delivering a medicant to an abnormal brain region and/or a malignant tumor - Google Patents

Method for using potassium channel agonists for delivering a medicant to an abnormal brain region and/or a malignant tumor Download PDF

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Publication number
WO2001054771A3
WO2001054771A3 PCT/US2001/002743 US0102743W WO0154771A3 WO 2001054771 A3 WO2001054771 A3 WO 2001054771A3 US 0102743 W US0102743 W US 0102743W WO 0154771 A3 WO0154771 A3 WO 0154771A3
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WO
WIPO (PCT)
Prior art keywords
medicant
potassium channel
activator
malignant tumor
brain region
Prior art date
Application number
PCT/US2001/002743
Other languages
French (fr)
Other versions
WO2001054771A2 (en
Inventor
Keith L Black
Nagendra S Ningaraj
Original Assignee
Cedars Sinai Medical Center
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 US09/491,500 external-priority patent/US7018979B1/en
Application filed by Cedars Sinai Medical Center filed Critical Cedars Sinai Medical Center
Priority to AU2001234602A priority Critical patent/AU2001234602A1/en
Priority to JP2001554753A priority patent/JP2003523965A/en
Priority to EP01906729A priority patent/EP1251838A2/en
Publication of WO2001054771A2 publication Critical patent/WO2001054771A2/en
Publication of WO2001054771A3 publication Critical patent/WO2001054771A3/en

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
    • C12N15/88—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using amphiphile liposome vesicle
    • 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
    • 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
    • A61K31/04—Nitro 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • 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
    • A61K31/28—Compounds containing heavy metals
    • A61K31/282—Platinum 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
    • A61K31/28—Compounds containing heavy metals
    • A61K31/295—Iron group metal 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4245—Oxadiazoles
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated 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
    • A61K31/33—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
    • A61K31/475—Quinolines; Isoquinolines having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine
    • 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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
    • 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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • 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
    • A61K31/655—Azo (—N=N—), diazo (=N2), azoxy (>N—O—N< or N(=O)—N<), azido (—N3) or diazoamino (—N=N—N<) 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
    • A61K31/66—Phosphorus compounds
    • A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
    • 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
    • A61K31/69—Boron compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • 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
    • 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

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Genetics & Genomics (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • General Engineering & Computer Science (AREA)
  • Physics & Mathematics (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Plant Pathology (AREA)
  • Oncology (AREA)
  • Microbiology (AREA)
  • Communicable Diseases (AREA)
  • Emergency Medicine (AREA)
  • Biochemistry (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Inorganic Chemistry (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

Disclosed are methods of selectively delivering a medicant to an abnormal brain region and/or to a malignant tumor in a mammalian subject, including a human. A medicant is administered simultaneously or substantially simultaneously with a calcium- or ATP-dependent potassium channel [KCa or KATP] activator (other than bradykinin or a bradykinin analog), such as a direct potassium channel agonist or an indirect potassium channel activator, such as an activator of soluble guanylyl cyclase (e.g., nitric oxide or a nitric oxide donor) or an activator of cyclic GMP-dependent protein kinase, whereby the medicant is delivered selectively to the cells of the abnormal brain region and/or to the tumor, compared to normal tissues. Thus, among the disclosures is a method of treating a malignant tumor in a human subject. Also disclosed are pharmaceutical compositions that combine a potassium channel activator together with a medicant and a kit for enhancing the delivery of a medicant to an abnormal brain region and/or to a malignant tumor.
PCT/US2001/002743 2000-01-26 2001-01-26 Method for using potassium channel agonists for delivering a medicant to an abnormal brain region and/or a malignant tumor WO2001054771A2 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
AU2001234602A AU2001234602A1 (en) 2000-01-26 2001-01-26 Method for using potassium channel agonists for delivering medicant to an abnormal brain region and/or a malignant tumor
JP2001554753A JP2003523965A (en) 2000-01-26 2001-01-26 Methods of using potassium channel agonists to deliver drugs to abnormal brain regions and / or malignancies
EP01906729A EP1251838A2 (en) 2000-01-26 2001-01-26 Method for using potassium channel agonists for delivering a medicant to an abnormal brain region and/or a malignant tumor

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US09/491,500 US7018979B1 (en) 2000-01-26 2000-01-26 Method for using potassium channel agonists for delivering a medicant to an abnormal brain region and/or a malignant tumor
US09/491,500 2000-01-26
US61585400A 2000-07-14 2000-07-14
US09/615,854 2000-07-14

Publications (2)

Publication Number Publication Date
WO2001054771A2 WO2001054771A2 (en) 2001-08-02
WO2001054771A3 true WO2001054771A3 (en) 2002-06-20

Family

ID=27050462

Family Applications (2)

Application Number Title Priority Date Filing Date
PCT/US2001/002742 WO2001054680A2 (en) 2000-01-26 2001-01-26 Method for using potassium channel activation for delivering a medicant to an abnormal brain region and/or a malignant tumor
PCT/US2001/002743 WO2001054771A2 (en) 2000-01-26 2001-01-26 Method for using potassium channel agonists for delivering a medicant to an abnormal brain region and/or a malignant tumor

Family Applications Before (1)

Application Number Title Priority Date Filing Date
PCT/US2001/002742 WO2001054680A2 (en) 2000-01-26 2001-01-26 Method for using potassium channel activation for delivering a medicant to an abnormal brain region and/or a malignant tumor

Country Status (4)

Country Link
EP (1) EP1251840A2 (en)
JP (2) JP2003523965A (en)
AU (2) AU2001233052A1 (en)
WO (2) WO2001054680A2 (en)

Families Citing this family (25)

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JP2003531179A (en) 2000-04-26 2003-10-21 クイーンズ ユニバーシティ アット キングストン Formulations and methods of using nitric oxide mimetics for malignant cell phenotype
US7678391B2 (en) 2000-04-26 2010-03-16 Queen's University At Kingston Formulations and methods of using nitric oxide mimetics against a malignant cell phenotype
GB0021487D0 (en) * 2000-09-01 2000-10-18 Pfizer Ltd Pharmaceutical
US7049334B2 (en) * 2001-09-14 2006-05-23 Carlsbad Technology, Inc. Enhancement of learning and memory and treatment of amnesia
US7211561B2 (en) * 2001-10-12 2007-05-01 Cedars-Sinai Medical Center Method for inducing selective cell death of malignant cells by activation of calcium-activated potassium channels (KCa)
AU2003208228A1 (en) * 2002-03-06 2003-09-16 Cellegy Pharmaceuticals, Inc Formulations and methods of using nitric oxide mimetics in cancer treatment
US8980952B2 (en) 2002-03-20 2015-03-17 University Of Maryland, Baltimore Methods for treating brain swelling with a compound that blocks a non-selective cation channel
ES2436467T3 (en) 2002-03-20 2014-01-02 University Of Maryland Baltimore A non-selective cationic channel in neural cells and antagonists of Sur1 for the treatment of brain inflammation
US7166293B2 (en) * 2002-03-29 2007-01-23 Carlsbad Technology, Inc. Angiogenesis inhibitors
EP1519923A1 (en) * 2002-06-26 2005-04-06 Poseidon Pharmaceuticals A/S Novel benzimidazol-2-one derivatives and their use
DE10240735A1 (en) * 2002-08-29 2004-03-18 Eberhard-Karls-Universität Tübingen Universitätsklinikum Regulating human endostatin expression, e.g. for treating CNS disorders or tumors, using nitrogen monoxide signal cascade modulators
ES2222831B2 (en) * 2003-07-30 2006-02-16 Laboratorios Del Dr. Esteve, S.A. COMBINATION OF ACTIVE PRINCIPLE THAT INCLUDES A 2,5-DIHYDROXIBENCENOSULPHONE COMPOUND AND A K + CHANNEL MODULATOR.
EP1663239A4 (en) * 2003-09-10 2008-07-23 Cedars Sinai Medical Center Potassium channel mediated delivery of agents through the blood-brain barrier
WO2005120493A1 (en) 2004-06-10 2005-12-22 Tohoku University Anticancer effect enhancer
JP5307397B2 (en) 2004-09-18 2013-10-02 ユニバーシティ オブ メリーランド，ボルチモア Therapeutic agent targeting NCCa-ATP channel and method of use thereof
ATE487484T1 (en) 2004-09-18 2010-11-15 Univ Maryland THERAPEUTIC AGENTS FOR TARGETING THE NC CA ATP CHANNEL AND METHOD OF USE THEREOF
US20070026079A1 (en) * 2005-02-14 2007-02-01 Louis Herlands Intranasal administration of modulators of hypothalamic ATP-sensitive potassium channels
WO2006091587A2 (en) * 2005-02-22 2006-08-31 Cedars-Sinai Medical Center Use of minoxidil sulfate as an anti-tumor drug
DK1896421T3 (en) * 2005-06-23 2012-01-09 Merck Sharp & Dohme Benzocyclohetapyridines as inhibitors of the receptor tyrosine kinase MET
EP2111224B1 (en) 2007-01-12 2016-07-13 University of Maryland, Baltimore Targeting ncca-atp channel for organ protection following ischemic episode
US8557867B2 (en) 2007-06-22 2013-10-15 The United States Of America As Represented By The Department Of Veterans Affairs Inhibitors of NCCa-ATP channels for therapy
AU2009244790B2 (en) * 2008-05-09 2013-09-12 Duke University Treatment for diseases relying on discovery that thioredoxin mediates nitric oxide release in cells
GB0921525D0 (en) * 2009-12-08 2010-01-27 Isis Innovation Product and method
KR102282716B1 (en) * 2020-02-07 2021-07-29 포항공과대학교 산학협력단 Composition for increasing permeability of blood-brain barrier comprising nitric oxide donor and use thereof
KR102490837B1 (en) * 2020-03-19 2023-01-19 포항공과대학교 산학협력단 Method for increasing permeability of blood-brain barrier

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EP0351767A2 (en) * 1988-07-18 1990-01-24 E.R. SQUIBB &amp; SONS, INC. Use of potassium channel activators to inhibit myocardial cell necrosis and to maintain the functioning of the heart during myocardial ischemia and/or reperfusion
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EP0575749A2 (en) * 1992-06-11 1993-12-29 E.R. SQUIBB &amp; SONS, INC. Use of potassium-channel activators for the manufacture of a medicament for the treatment of gastrointertinal ulcers
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W. G. MAYHAN: "Role of nitric oxide in histamine-induced increases in permeability of the blood-brain barrier", BRAIN RESEARCH, vol. 743, 1996, pages 70 - 76, XP002195900 *

Also Published As

Publication number Publication date
WO2001054680A2 (en) 2001-08-02
AU2001234602A1 (en) 2001-08-07
JP2003523965A (en) 2003-08-12
AU2001233052A1 (en) 2001-08-07
WO2001054680A3 (en) 2002-06-27
WO2001054771A2 (en) 2001-08-02
JP2004508279A (en) 2004-03-18
EP1251840A2 (en) 2002-10-30

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