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WO1997009976A2 - Procede d'attenuation de troubles dus a des neurotoxines par des chelatants du zinc - Google Patents

Procede d'attenuation de troubles dus a des neurotoxines par des chelatants du zinc Download PDF

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Publication number
WO1997009976A2
WO1997009976A2 PCT/IB1996/000981 IB9600981W WO9709976A2 WO 1997009976 A2 WO1997009976 A2 WO 1997009976A2 IB 9600981 W IB9600981 W IB 9600981W WO 9709976 A2 WO9709976 A2 WO 9709976A2
Authority
WO
WIPO (PCT)
Prior art keywords
zinc chelating
zinc
pharmaceutically acceptable
disease
injury
Prior art date
Application number
PCT/IB1996/000981
Other languages
English (en)
Other versions
WO1997009976A3 (fr
Inventor
Dennis Wonkyu Choi
Jae-Young Koh
Original Assignee
Washington University
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 Washington University filed Critical Washington University
Priority to AU68879/96A priority Critical patent/AU6887996A/en
Publication of WO1997009976A2 publication Critical patent/WO1997009976A2/fr
Publication of WO1997009976A3 publication Critical patent/WO1997009976A3/fr

Links

Classifications

    • 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
    • A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/17—Amides, e.g. hydroxamic acids having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine
    • 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
    • A61K31/325—Carbamic acids; Thiocarbamic acids; Anhydrides or salts 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
    • A61K31/41—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
    • A61K31/42—Oxazoles
    • A61K31/422—Oxazoles not condensed and containing further 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
    • A61K31/33—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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
    • 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

Definitions

  • the invention relates to the use of zinc chelating compounds in the treatment of neurotoxic injury.
  • the present invention comprises a method of treating neurotoxic injury in a patient suffering said injury, comprising administering to said patient a zinc chelating compound in an amount sufficient to treat said neurotoxic injury.
  • composition comprising the zinc chelating compound
  • administration of the composition comprising the zinc chelating compound is carried out by injection or infusion of the composition into the patients cerebrospinal fluid.
  • Chelatable Zn ⁇ + is present in large quantities in presynaptic vesicles of central excitatory neurons (Danscher et al., 1985; Frederickson et al., 1983), and released with synaptic activity or membrane depolarization (Assaf and Chung, 1984; Howell et al., 1984; Charton et al., 1985). Although the precise role of released synaptic zinc is not known, it blocks NMDA receptor- mediated current (Westbrook and Mayer, 1987; Peters et al., 1987; Christine and Choi, 1990) and GABA receptor-mediated current (Westbrook and
  • Treating neurotoxic injury within the meaning of the present invention means reducing the extent of damage to central neurons surrounding a central neuron which has released Zn + due to its having been damaged by a neurotoxic event.
  • Neurotoxic events include acute neurological insults such as hypoxia/ischemia, such as occurs during stroke, cardiac arrest, hypoglycemia, epilepsy or trauma.
  • Neurotoxic events may also be chronic neuronal damage caused by neurodegenerative disorders such as Huntington's disease, Alzheimer's disease, amyotropic lateral sclerosis, and the neurodegenerative effects of AIDS.
  • the present invention also comprises a method of treating diseases, such as those described above, in which said neurotoxic injury occurs.
  • the zinc chelating compounds useful in accordance with the invention are not critical. Any conventional compound which is capable of chelating Zn 2+ and which is pharmaceutically acceptable for injection into cerebral spinal fluid may be used in accordance with the invention.
  • EDTA ethylenediaminetetraacetic acid
  • the preferred zinc chelating compound for use in accordance with the invention is disodium- calcium EDTA ("CaEDTA”), especially the form of CaEDTA known as edetate calcium disodium injection, USP (e.g., Calcium Disodium Versenate, 3M Pharmaceuticals, St. Paul, Minnesota).
  • CaEDTA disodium- calcium EDTA
  • USP e.g., Calcium Disodium Versenate, 3M Pharmaceuticals, St. Paul, Minnesota
  • Another preferred zinc chelating compound useful in accordance with the invention is 3-mercapto-D-valine (penicillamine), which is a chelating agent usually applied to the treatment of Wilson's disease where it removes excess copper.
  • TPEN N,N,N',N'-tetrakis(2-pyridylmethyl)-ethylenediamine
  • the zinc chelating compound used in accordance with the present invention may be administered to the cerebrospinal fluid by any conventional means.
  • the preferred method of administration is by injection or chronic pump infusion into the lateral ventricles of the patient's brain or into the lumbar sac of the patient.
  • the zinc chelating compound is preferably administered as a composition containing the zinc chelating compound and a pharmaceutically acceptable carrier compatible with the compound.
  • any conventional pharmaceutically acceptable carrier may be utilized.
  • Typical carriers for administration by injection would be sterile aqueous/buffered solutions, preferably water for injecion or unbuffered or buffered physiological saline.
  • the zinc chelating compound is preferably present in the carrier at a concentration of 1 mM - 300 mM, especially from 50 mM - 200 mM.
  • the zinc chelating compound is administered to adults daily in an amount from about 0.1 mg/kg to about 100 mg/kg daily, in single or divided doses, or continuously through chronic pump infusion.
  • the preferred dosage will vary depending upon the indication for which the method of the invention is being used to treat.
  • the administration of a dosage from about 5 mg/kg to about 50 mg/kg daily, carried out for from 1 to 7 days, is preferred.
  • Administration may be carried out by injection or by infusion utilizing a chronic infusion pump.
  • a dosage of from aboutl mg/kg to about 10 mg/kg daily is preferred, carried out for months to years, preferably utilizing a chronic infusion pump.
  • the present invention also comprises a method of treating neurotoxic injury in a patient suffering said injury by administering to said patient a composition comprising a zinc chelating compound and carrier, wherein both the compound and the carrier are pharmaceutically acceptable for injection.
  • the prefered zinc chelating compounds are CaEDTA and 3- mercapto-D-valine, with CaEDTA being especially preferred.
  • the zinc chelating compound is preferably administered in an amount from about 01. mg/kg to about 100 mg/kg daily, especially in an amount from about 5 mg/kg to about 50 mg/kg daily for the treatment of acute neurotoxic conditions and in an amount from about 1 mg/kg to about 10 mg/kg daily for chronic neurotoxic conditions.
  • the preferred method of administration is the injection or infusion of the pharmaceutical composition comprising the zinc chelating compound and the carrier into the cerebrospinal fluid (e.g., the lateral ventricles or lumbar sac) of the patient.
  • the preferred duration of treatment is from 1 to 7 days for acute neurotoxic cond tions, and for months to years for chronic neurotoxic conditions.
  • the present invention preferably comprises a method of treating stroke in a patient suffering said stroke by administering to said patient a composition comprising a zinc chelating compound and a carrier, wherein both the compound and the carrier are pharmaceutically acceptable for injection.
  • the preferred zinc chelating compounds are CaEDTA and 3- mercapto-D-valine, with CaEDTA being especially preferred.
  • the zinc chelating compound is preferably administered in an amount from about 0.1 mg/kg to about 100 mg/kg daily, especially in an amount from about 5 mg/kg to about 50 mg/kg daily for the treatment of stroke.
  • the preferred method of administration is the injection or infusion, especially injection, of the pharmaceutical composition comprising the zinc chelating compound and the carrier into the cerebrospinal fluid (e.g., the lateral ventricles or lumbar sac) ofthe patient.
  • the preferred duration of treatment is from 1 to 7 days.
  • CaEDTA selectively blocks Zn ⁇ +- induced neuronal degeneration, but not the Ca2+-overload neurotoxicity induced by glutamate agonists.
  • CaEDTA disodium-calcium-EDTA
  • Hippocampal sections from the treated and untreated rats were stained with the zinc-sensitive dye, TSQ (Frederickson et al., 1987). The examination of these sections showed that in the untreated rats zinc translocated from presynaptic inputs to degenerating hilar neuronal cell bodies between 3-24 hours after the ischemia. In the treated rats, CaEDTA blocked not only this zinc translocation, but also prevented subsequent hilar neuronal degeneration as assessed 3 days later.
  • TSQ staining also revealed the delayed appearance of zinc in CA1 pyramidal neuronal cell bodies of untreated rats 24-72 hours post ischemia.
  • the CaEDTA treatment prior to the induced ischemia attenuated both the appearance of zinc in CA1 pyramidal neurons, and CA1 neuronal degeneration.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

L'invention porte sur des composés chélatants du zinc pharmaceutiquement acceptables, utilisés dans la fabrication de médicaments destinés au traitement de troubles dus à des neurotoxines.
PCT/IB1996/000981 1995-09-01 1996-08-23 Procede d'attenuation de troubles dus a des neurotoxines par des chelatants du zinc WO1997009976A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU68879/96A AU6887996A (en) 1995-09-01 1996-08-23 Method of reducing neurotoxic injury with zinc chelators

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US313495P 1995-09-01 1995-09-01
US60/003,134 1995-09-01
US735695P 1995-11-20 1995-11-20
US60/007,356 1995-11-20

Publications (2)

Publication Number Publication Date
WO1997009976A2 true WO1997009976A2 (fr) 1997-03-20
WO1997009976A3 WO1997009976A3 (fr) 1997-05-22

Family

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Application Number Title Priority Date Filing Date
PCT/IB1996/000981 WO1997009976A2 (fr) 1995-09-01 1996-08-23 Procede d'attenuation de troubles dus a des neurotoxines par des chelatants du zinc

Country Status (2)

Country Link
AU (1) AU6887996A (fr)
WO (1) WO1997009976A2 (fr)

Cited By (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999045907A3 (fr) * 1998-03-11 2000-04-06 Gen Hospital Corp Agents utilises pour traiter la maladie d'alzheimer
WO2000071101A3 (fr) * 1999-05-24 2001-12-06 Univ Kingston Procedes et composes permettant d'inhiber les depots amyloides
US6407090B1 (en) 1999-06-23 2002-06-18 Zinc Therapeutics Canada, Inc. Zinc ionophores as anti-apoptotic agents
EP0893951A4 (fr) * 1996-01-26 2003-04-23 Univ California PROCEDES DE MODULATION DE LA FORMATION DE RADICAUX PAR UTILISATION D'ENZYMES CuZnSOD MUTANTES
US6638711B1 (en) 1999-04-29 2003-10-28 The General Hospital Corporation Methods for identifying an agent that inhibits oxygen-dependent hydrogen peroxide formation activity but does not inhibit superoxide-dependent hydrogen peroxide formation
WO2004091518A3 (fr) * 2003-04-11 2004-12-23 Anormed Inc Composes de liaison aux recepteurs de chimiokine cxcr4
JP2006504646A (ja) * 2002-07-16 2006-02-09 プラナ バイオテクノロジー リミティッド ８−ヒドロキシキノリン誘導体
US7045531B1 (en) 1997-03-11 2006-05-16 The General Hospital Corporation Composition comprising a metal chelator and a method of treating amyloidosis by administering the metal chelator
EP1546085A4 (fr) * 2002-09-25 2008-03-26 Dpharm Ltd Diesters lipophiles d'un agent chelateur inhibiteurs d'activites enzymatiques
EP2295059A3 (fr) * 2001-12-06 2013-04-03 Fibrogen, Inc. Stabilisation du facteur alpha inducteur d'hypoxie
WO2016164685A1 (fr) * 2015-04-10 2016-10-13 Ohio University Compositions et méthodes destinées à des tissus traumatisés, comprenant des chélateurs du zinc
WO2016179217A1 (fr) * 2015-05-06 2016-11-10 Ohio University Chélation d'ions métalliques pour améliorer l'effet d'un activateur tissulaire du plasminogène (tpa) dans le cadre de la thrombolyse
US9499480B2 (en) 2006-10-12 2016-11-22 Bhi Limited Partnership Methods, compounds, compositions and vehicles for delivering 3-amino-1-propanesulfonic acid
US10369108B2 (en) 2013-03-15 2019-08-06 Mylan Laboratories, Inc. Hot melt granulation formulations of poorly water-soluble active agents
US10548889B1 (en) 2018-08-31 2020-02-04 X4 Pharmaceuticals, Inc. Compositions of CXCR4 inhibitors and methods of preparation and use
US10610527B2 (en) 2015-12-22 2020-04-07 X4 Pharmaceuticals, Inc. Methods for treating immunodeficiency disease
US10759796B2 (en) 2016-06-21 2020-09-01 X4 Pharmaceuticals, Inc. CXCR4 inhibitors and uses thereof
US10953003B2 (en) 2015-12-14 2021-03-23 X4 Pharmaceuticals, Inc. Methods for treating cancer
US10988465B2 (en) 2016-06-21 2021-04-27 X4 Pharmaceuticals, Inc. CXCR4 inhibitors and uses thereof
US11332470B2 (en) 2016-06-21 2022-05-17 X4 Pharmaceuticals, Inc. CXCR4 inhibitors and uses thereof
US11337969B2 (en) 2016-04-08 2022-05-24 X4 Pharmaceuticals, Inc. Methods for treating cancer
US11357742B2 (en) 2015-12-14 2022-06-14 X4 Pharmaceuticals, Inc. Methods for treating cancer
US12285424B2 (en) 2020-03-10 2025-04-29 X4 Pharmaceuticals, Inc. Methods for treating neutropenia

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US7414076B2 (en) 2003-06-23 2008-08-19 Neurochem (International) Limited Methods and compositions for treating amyloid-related diseases
US7244764B2 (en) 2003-06-23 2007-07-17 Neurochem (International) Limited Methods and compositions for treating amyloid-related diseases
CN101128421A (zh) 2004-12-22 2008-02-20 神经化学（国际）有限公司 治疗淀粉样相关疾病用的方法与组合物

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DE3932338A1 (de) * 1989-09-28 1991-04-11 Nmi Naturwissenschaftl U Mediz Verfahren zur praeventiven therapie von morbus alzheimer
US5206264A (en) * 1991-11-04 1993-04-27 Cypros Pharmaceutical Corporation Use of disulfiram to prevent cardiovascular damage
WO1993010459A1 (fr) * 1991-11-12 1993-05-27 The University Of Melbourne Procede de diagnostic et de traitement de la maladie d'alzheimer
GB9324871D0 (en) * 1993-12-03 1994-01-19 Lilly Industries Ltd Novel compounds
DE4431175A1 (de) * 1994-09-01 1996-04-11 Medico Pharma Vertriebs Gmbh Neue, Chelatbildner enthaltende Arzneimittel

Cited By (42)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0893951A4 (fr) * 1996-01-26 2003-04-23 Univ California PROCEDES DE MODULATION DE LA FORMATION DE RADICAUX PAR UTILISATION D'ENZYMES CuZnSOD MUTANTES
US7045531B1 (en) 1997-03-11 2006-05-16 The General Hospital Corporation Composition comprising a metal chelator and a method of treating amyloidosis by administering the metal chelator
US6323218B1 (en) 1998-03-11 2001-11-27 The General Hospital Corporation Agents for use in the treatment of Alzheimer's disease
WO1999045907A3 (fr) * 1998-03-11 2000-04-06 Gen Hospital Corp Agents utilises pour traiter la maladie d'alzheimer
JP2002506020A (ja) * 1998-03-11 2002-02-26 ザ・ジェネラル・ホスピタル・コーポレイション アルツハイマー病の治療に用いるための剤
US6638711B1 (en) 1999-04-29 2003-10-28 The General Hospital Corporation Methods for identifying an agent that inhibits oxygen-dependent hydrogen peroxide formation activity but does not inhibit superoxide-dependent hydrogen peroxide formation
US6562836B1 (en) 1999-05-24 2003-05-13 Queen's University Of Kingston Methods and compounds for inhibiting amyloid deposits
CN100435785C (zh) * 1999-05-24 2008-11-26 贝卢斯健康(国际）有限公司 抑制iapp的化合物或其可药用酯或其可药用盐的制药应用
US7786174B2 (en) 1999-05-24 2010-08-31 Bellus Health (International) Limited Methods and compounds for inhibiting amyloid deposits
WO2000071101A3 (fr) * 1999-05-24 2001-12-06 Univ Kingston Procedes et composes permettant d'inhiber les depots amyloides
US7393875B2 (en) 1999-05-24 2008-07-01 Neurochem (International) Limited Methods and compounds for inhibiting amyloid deposits
US6407090B1 (en) 1999-06-23 2002-06-18 Zinc Therapeutics Canada, Inc. Zinc ionophores as anti-apoptotic agents
EP2295059A3 (fr) * 2001-12-06 2013-04-03 Fibrogen, Inc. Stabilisation du facteur alpha inducteur d'hypoxie
JP2006504646A (ja) * 2002-07-16 2006-02-09 プラナ バイオテクノロジー リミティッド ８−ヒドロキシキノリン誘導体
EP1546085A4 (fr) * 2002-09-25 2008-03-26 Dpharm Ltd Diesters lipophiles d'un agent chelateur inhibiteurs d'activites enzymatiques
US7799831B2 (en) 2002-09-25 2010-09-21 D-Pharm Ltd. Lipophilic diesters of chelating agent for inhibition of enzyme activity
US7291631B2 (en) 2003-04-11 2007-11-06 Genzyme Corporation CXCR4 chemokine receptor binding compounds
US7863293B2 (en) 2003-04-11 2011-01-04 Genzyme Corporation CXCR4 chemokine receptor binding compounds
WO2004091518A3 (fr) * 2003-04-11 2004-12-23 Anormed Inc Composes de liaison aux recepteurs de chimiokine cxcr4
US11020360B2 (en) 2006-10-12 2021-06-01 Bellus Health Inc. Methods, compounds, compositions and vehicles for delivering 3-amino-1-propanesulfonic acid
US9499480B2 (en) 2006-10-12 2016-11-22 Bhi Limited Partnership Methods, compounds, compositions and vehicles for delivering 3-amino-1-propanesulfonic acid
US10238611B2 (en) 2006-10-12 2019-03-26 Bellus Health Inc. Methods, compounds, compositions and vehicles for delivering 3-amino-1-propanesulfonic acid
US10857109B2 (en) 2006-10-12 2020-12-08 Bellus Health, Inc. Methods, compounds, compositions and vehicles for delivering 3-amino-1-propanesulfonic acid
US10369108B2 (en) 2013-03-15 2019-08-06 Mylan Laboratories, Inc. Hot melt granulation formulations of poorly water-soluble active agents
WO2016164685A1 (fr) * 2015-04-10 2016-10-13 Ohio University Compositions et méthodes destinées à des tissus traumatisés, comprenant des chélateurs du zinc
WO2016179217A1 (fr) * 2015-05-06 2016-11-10 Ohio University Chélation d'ions métalliques pour améliorer l'effet d'un activateur tissulaire du plasminogène (tpa) dans le cadre de la thrombolyse
US10953003B2 (en) 2015-12-14 2021-03-23 X4 Pharmaceuticals, Inc. Methods for treating cancer
US11357742B2 (en) 2015-12-14 2022-06-14 X4 Pharmaceuticals, Inc. Methods for treating cancer
US10610527B2 (en) 2015-12-22 2020-04-07 X4 Pharmaceuticals, Inc. Methods for treating immunodeficiency disease
US11219621B2 (en) 2015-12-22 2022-01-11 X4 Pharmaceuticals, Inc. Methods for treating immunodeficiency disease
US11337969B2 (en) 2016-04-08 2022-05-24 X4 Pharmaceuticals, Inc. Methods for treating cancer
US10759796B2 (en) 2016-06-21 2020-09-01 X4 Pharmaceuticals, Inc. CXCR4 inhibitors and uses thereof
US11306088B2 (en) 2016-06-21 2022-04-19 X4 Pharmaceuticals, Inc. CXCR4 inhibitors and uses thereof
US11332470B2 (en) 2016-06-21 2022-05-17 X4 Pharmaceuticals, Inc. CXCR4 inhibitors and uses thereof
US10988465B2 (en) 2016-06-21 2021-04-27 X4 Pharmaceuticals, Inc. CXCR4 inhibitors and uses thereof
US11780837B2 (en) 2016-06-21 2023-10-10 X4 Pharmaceuticals, Inc. CXCR4 inhibitors and uses thereof
US11045461B2 (en) 2018-08-31 2021-06-29 X4 Pharmaceuticals, Inc. Compositions of CXCR4 inhibitors and methods of preparation and use
US10548889B1 (en) 2018-08-31 2020-02-04 X4 Pharmaceuticals, Inc. Compositions of CXCR4 inhibitors and methods of preparation and use
US11672793B2 (en) 2018-08-31 2023-06-13 X4 Pharmaceuticals, Inc. Compositions of CXCR4 inhibitors and methods of preparation and use
US12115156B2 (en) 2018-08-31 2024-10-15 X4 Pharmaceuticals, Inc. Compositions of CXCR4 inhibitors and methods of preparation and use
US12285424B2 (en) 2020-03-10 2025-04-29 X4 Pharmaceuticals, Inc. Methods for treating neutropenia
US12377090B1 (en) 2020-03-10 2025-08-05 X4 Pharmaceuticals, Inc. Methods for treating neutropenia

Also Published As

Publication number Publication date
AU6887996A (en) 1997-04-01
WO1997009976A3 (fr) 1997-05-22

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