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

Info

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
Authority
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 EP01906729A priority patent/EP1251838A2/en
Priority to JP2001554753A priority patent/JP2003523965A/en
Publication of WO2001054771A2 publication Critical patent/WO2001054771A2/en
Publication of WO2001054771A3 publication Critical patent/WO2001054771A3/en

Links

Classifications

    • 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, pantothenic acid
    • A61K31/198—Alpha-aminoacids, e.g. alanine, edetic acids [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

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
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
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

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US09/491,500 2000-01-26
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
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) AU2001234602A1 (en)
WO (2) WO2001054680A2 (en)

Families Citing this family (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU5022101A (en) 2000-04-26 2001-11-07 Univ Kingston Formulations and methods of using nitric oxide mimetics against a malignant cellphenotype
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)
JP2005527510A (en) * 2002-03-06 2005-09-15 セレジー ファーマシューティカルズ インコーポレーティッド Formulations and methods for using nitric oxide mimetics in the treatment of cancer
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
US20030215889A1 (en) 2002-03-20 2003-11-20 Simard J. Marc Non-selective cation channel in neural cells and methods for treating brain swelling
US7166293B2 (en) 2002-03-29 2007-01-23 Carlsbad Technology, Inc. Angiogenesis inhibitors
AU2003240427A1 (en) 2002-06-26 2004-01-19 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
ES2338022T3 (en) 2004-06-10 2010-05-03 Nippon Kayaku Kabushiki Kaisha POTENTIAL OF THE ANTINEOPLASIC EFFECT.
AU2005290238A1 (en) * 2004-09-18 2006-04-06 Department Of Veterans Affairs Therapeutic agents trageting the NCCa-ATP channel and methods of use thereof
AU2005287090A1 (en) 2004-09-18 2006-03-30 Department Of Veterans Affairs Therapeutic agents targeting the NCca-ATP channel and methods 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
JP4119478B1 (en) * 2005-06-23 2008-07-16 メルク エンド カムパニー インコーポレーテッド Tyrosine kinase inhibitor
WO2008089103A2 (en) 2007-01-12 2008-07-24 University Of Maryland, Baltimore Targeting ncca-atp channel for organ protection following ischemic episode
CA3065983C (en) 2007-06-22 2022-07-26 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

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
WO1991016355A1 (en) * 1990-04-23 1991-10-31 Alkermes, Inc. Method for increasing blood-brain barrier permeability
EP0555681A1 (en) * 1992-02-13 1993-08-18 E.R. SQUIBB &amp; SONS, INC. Use of a combination of potassium channel activators and sulfhydryl containing compounds for the manufacture of a medicament for the treatment of ischemia and myocarolial infarct
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
WO1997031654A1 (en) * 1996-02-26 1997-09-04 Nicox S.A. Nitric oxide donors capable of reducing toxicity from drugs
WO2000023102A1 (en) * 1998-10-19 2000-04-27 New York University Method for regulating the permeability of the blood brain barrier

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
WO1991016355A1 (en) * 1990-04-23 1991-10-31 Alkermes, Inc. Method for increasing blood-brain barrier permeability
US5112596A (en) * 1990-04-23 1992-05-12 Alkermes, Inc. Method for increasing blood-brain barrier permeability by administering a bradykinin agonist of blood-brain barrier permeability
EP0555681A1 (en) * 1992-02-13 1993-08-18 E.R. SQUIBB &amp; SONS, INC. Use of a combination of potassium channel activators and sulfhydryl containing compounds for the manufacture of a medicament for the treatment of ischemia and myocarolial infarct
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
WO1997031654A1 (en) * 1996-02-26 1997-09-04 Nicox S.A. Nitric oxide donors capable of reducing toxicity from drugs
WO2000023102A1 (en) * 1998-10-19 2000-04-27 New York University Method for regulating the permeability of the blood brain barrier

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
OAK Z. CHI ET AL: "Effects of Cyclic GMP on Microvascular Permeability of the Cerebral Cortex", MICROVASCULAR RESEARCH, vol. 58, 1999, pages 35 - 40, XP002195899 *
R. T. BARTUS ET AL: "Controlled Modulation of BBB Permeability Using the Bradykinin Agonist, RMP-7", EXPERIMENTAL NEUROLOGY, vol. 142, 1996, pages 14 - 28, XP002195901 *
See also references of EP1251838A2 *
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
WO2001054771A2 (en) 2001-08-02
WO2001054680A3 (en) 2002-06-27
AU2001233052A1 (en) 2001-08-07
WO2001054680A2 (en) 2001-08-02
JP2004508279A (en) 2004-03-18
JP2003523965A (en) 2003-08-12
AU2001234602A1 (en) 2001-08-07
EP1251840A2 (en) 2002-10-30

Similar Documents

Publication Publication Date Title
WO2001054771A3 (en) Method for using potassium channel agonists for delivering a medicant to an abnormal brain region and/or a malignant tumor
EP1287830B1 (en) Use of methioninase as an antitumor agent in anti-methionine chemotherapy
WO2003053346A3 (en) Systems and methods for treating patients with processed lipoaspirate cells
CA2413337A1 (en) Bioadhesive compositions and methods of preparation and use
EP0783299A4 (en) Compounds and compositions for delivering active agents
WO2005120407A3 (en) Preparation for localized delivery of therapeutic agent
MXPA05006169A (en) Compositions and methods of delivery of pharmacological agents.
WO2001091728A3 (en) Nanoemulsion formulations
WO2005004895A3 (en) Compositions and methods for enhanced mucosal delivery of growth hormone
WO1996025947A3 (en) Induction of e-selectin for targetting therapeutic agents
AU2624400A (en) Monodisperse hexameric acylated insulin analog formulations
AU8180001A (en) Human growth hormone to stimulate mobilization of pluripotent hematopoietic stemcells
IE882091L (en) Pharmaceutical compositions comprising sometostatin¹analogues
IL157841A0 (en) Activation of natural killer cells by adenosine a3 receptor agonists
WO2003063780A3 (en) Therapeutic composition for treatment of cancer by arginine depletion
ATE156492T1 (en) BOMB ANALOGUES
WO2003033678A3 (en) Methods of using deacetylase inhibitors to promote cell differentiation and regeneration
WO1997042968A3 (en) Administration of histamine for therapeutic purposes
WO2002058589A3 (en) Agents and methods for promoting bone growth
TNSN04235A1 (en) Compositions for therapeutic use comprising a vitamin, a metal salt and insulin or a growth hormone
NO942919L (en) Bombesin phenylalanine analogues
Nicosia et al. Effects of vasoactive intestinal polypeptide (VIP) in human prolactin (PRL) secreting pituitary adenomas: Stimulation of PRL release and activation of adenylate cyclase
US20090252684A1 (en) Determination of tissue-specific profile of amino acid requirements form the relationship between the amounts of tRNAs for individual amino acids and the protein-bound amino acid profile of the tissue
AU3908997A (en) Treatment of stress-induced skin disease by corticotropin releasing hormone antagonists and skin mast cell degranulation inhibitors
EP0788799A3 (en) LHRH-Antagonists in the treatment of fertility disorders

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CR CU CZ DE DK DM DZ EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
AK Designated states

Kind code of ref document: A3

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CR CU CZ DE DK DM DZ EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A3

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

ENP Entry into the national phase

Ref country code: JP

Ref document number: 2001 554753

Kind code of ref document: A

Format of ref document f/p: F

WWE Wipo information: entry into national phase

Ref document number: 2001906729

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 2001906729

Country of ref document: EP

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642