Abstract

This invention provides methods for treating endothelial dysfunction by administering an effective amount of citrulline to a patient. The patients may be suffering from acute respiratory distress syndrome (ARDS), sepsis, or infection by COVID-19 (Coronavirus Disease 2019); COVID-19 patients may be at risk of developing endothelial dysfunction, or they may be experiencing endothelial dysfunction. The effective amount of citrulline is sufficient to reduce the uncoupling of endothelial nitric oxide synthase (eNOS) or to reduce the formation of free radicals. Citrulline may be administered orally; intravenously; or both orally and intravenously in a sequential manner. Sequential administration of citrulline may be in three phases, such as (a) an initial phase in which citrulline is administered orally, (b) an intermediate phase wherein citrulline is administered intravenously, and (c) a final phase wherein citrulline is administered orally. The intermediate phase may be while the patient's breathing is being assisted mechanically.

IPC Classes  ?

• A61K 31/198 - Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
• A61P 11/00 - Drugs for disorders of the respiratory system
• A61P 31/14 - Antivirals for RNA viruses

Abstract

This invention is directed to citrulline therapy, where citrulline is administered to achieve a newly recognized therapeutic window. The results of a completed clinical trial has elucidated a therapeutic window for L-citrulline. Detailed analysis of clinical outcome as a function of the dose actually received reveals that patients falling within the dosing window showed significant improved effect compared to patients receiving a dose either below or above the dosing window. Patients benefiting from this invention are patients in need of supplemental citrulline to ensure that adequate nitric oxide levels are produced by endothelial tissues.

IPC Classes  ?

• A61K 31/198 - Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
• A61P 9/00 - Drugs for disorders of the cardiovascular system
• A61P 11/00 - Drugs for disorders of the respiratory system
• A61P 39/06 - Free radical scavengers or antioxidants

Abstract

This invention is directed to citrulline therapy, where citrulline is administered to achieve a newly recognized therapeutic window. The results of a completed clinical trial has elucidated a therapeutic window for L-citrulline. Detailed analysis of clinical outcome as a function of the dose actually received reveals that patients falling within the dosing window showed significant improved effect compared to patients receiving a dose either below or above the dosing window. Patients benefiting from this invention are patients in need of supplemental citrulline to ensure that adequate nitric oxide levels are produced by endothelial tissues.

IPC Classes  ?

• A61K 31/198 - Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
• A61K 35/14 - BloodArtificial blood
• A61P 41/00 - Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution

Abstract

This invention provides methods for treating endothelial dysfunction by administering an effective amount of citrulline to a patient. The patients may be suffering from acute respiratory distress syndrome (ARDS), sepsis, or infection by COVID-19 (Coronavirus Disease 2019); COVID-19 patients may be at risk of developing endothelial dysfunction, or they may be experiencing endothelial dysfunction. The effective amount of citrulline is sufficient to reduce the uncoupling of endothelial nitric oxide synthase (eNOS) or to reduce the formation of free radicals. Citrulline may be administered orally; intravenously; or both orally and intravenously in a sequential manner. Sequential administration of citrulline may be in three phases, such as (a) an initial phase in which citrulline is administered orally, (b) an intermediate phase wherein citrulline is administered intravenously, and (c) a final phase wherein citrulline is administered orally. The intermediate phase may be while the patient's breathing is being assisted mechanically.

IPC Classes  ?

• A61K 31/198 - Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
• A61P 9/08 - Vasodilators for multiple indications
• A61P 11/00 - Drugs for disorders of the respiratory system
• A61P 9/12 - Antihypertensives

Abstract

This invention provides methods for treating endothelial dysfunction by administering an effective amount of citrulline to a patient. The patients may be suffering from acute respiratory distress syndrome (ARDS), sepsis, or infection by COVID-19 (Coronavirus Disease 2019); COVID-19 patients may be at risk of developing endothelial dysfunction, or they may be experiencing endothelial dysfunction. The effective amount of citrulline is sufficient to reduce the uncoupling of endothelial nitric oxide synthase (eNOS) or to reduce the formation of free radicals. Citrulline may be administered orally; intravenously; or both orally and intravenously in a sequential manner. Sequential administration of citrulline may be in three phases, such as (a) an initial phase in which citrulline is administered orally, (b) an intermediate phase wherein citrulline is administered intravenously, and (c) a final phase wherein citrulline is administered orally. The intermediate phase may be while the patient's breathing is being assisted mechanically.

IPC Classes  ?

• A61K 31/198 - Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
• A61P 11/00 - Drugs for disorders of the respiratory system
• A61P 31/14 - Antivirals for RNA viruses

Abstract

This invention provides for synthesis of citrulline from a transition metal complex of ornithine using cyanate to derivatize the terminal amino group of ornithine. The invention also provides improved methods for purification of citrulline produced by reaction of cyanate with ornithine via the steps of reprecipitation of copper complex of citrulline, removal of the complexing metal by sulfide precipitation, activated carbon adsorption and antisolvent crystallization.

IPC Classes  ?

• C07C 273/16 - SeparationPurification
• A61K 9/00 - Medicinal preparations characterised by special physical form
• C07C 273/18 - Preparation of urea or its derivatives, i.e. compounds containing any of the groups the nitrogen atoms not being part of nitro or nitroso groups of substituted ureas

Goods & Services

Pharmaceutical preparations in the nature of preventatives for the treatment of acute lung injury induced by cardiopulmonary bypass in pediatric patients

Abstract

This invention provides for synthesis of citrulline from a transition metal complex of ornithine using cyanate to derivatize the terminal amino group of ornithine. The invention also provides improved methods for purification of citrulline produced by reaction of cyanate with ornithine via the steps of reprecipitation of copper complex of citrulline, removal of the complexing metal by sulfide precipitation, activated carbon adsorption and antisolvent crystallization.

IPC Classes  ?

• C07C 227/40 - SeparationPurification
• C07C 229/08 - Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to hydrogen atoms
• C07C 229/16 - Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of hydrocarbon radicals substituted by amino or carboxyl groups, e.g. ethylenediamine-tetra-acetic acid, iminodiacetic acids

Abstract

This invention provides for synthesis of citrulline from a transition metal complex of ornithine using cyanate to derivatize the terminal amino group of ornithine. The invention also provides improved methods for purification of citrulline produced by reaction of cyanate with ornithine via the steps of reprecipitation of copper complex of citrulline, removal of the complexing metal by sulfide precipitation, activated carbon adsorption and antisolvent crystallization.

IPC Classes  ?

• C07C 227/40 - SeparationPurification
• C07C 229/08 - Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to hydrogen atoms
• C07C 229/16 - Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of hydrocarbon radicals substituted by amino or carboxyl groups, e.g. ethylenediamine-tetra-acetic acid, iminodiacetic acids

Goods & Services

Pharmaceutical products in the nature of preventatives for acute lung injury induced by cardiopulmonary bypass in pediatric patients.

Goods & Services

pharmaceutical research and development