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US5286739A Expired / Lapsed US ⏱️ 0.0 years remaining

Parenteral formulations for the inhibition of systemic hypotension associated with nitric oxide production or endothelial derived relaxing factor

Assignee: Cornell Research Foundation Inc
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Filing: 1991-09-27
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Granted: 1994-02-15
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Expires: 2011-09-27
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Abstract

Abstract An anti-hypotensive formulation comprising an essentially arginine-free or low arginine (less than about 0.1%, most preferably, about 0.01%) containing mixture of amino acids is provided. The invention in particular embodiments of the anti-hypotensive formulation includes ornithine, citrulline or both. A method for prophylaxis and treatment of systemic hypotension in an animal is provided. Most particularly, a method for treating hypotension caused by nitric oxide synthesis through administering a low or essentially arginine-free parenteral formulation to an animal, so as to reduce or eliminate nitric oxide synthesis is described. A method for treating an animal in septic shock is also disclosed, comprising administering to the animal an anti-hypotensive formulation comprising a mixture of amino acids, which is essentially arginine free. Prophylaxis or treatment of systemic hypotension, particularly that hypotension incident to chemotherapeutic treatment with biologic response modifiers, such as tumor necrosis factor or interleukin-1 or -2, may be accomplished through the administration of the defined anti-hypotensive formulations until physiologically acceptable systolic blood pressure levels are achieved in the animal. Treatment of an animal for septic shock induced by endotoxin may also be accomplished by administering to the animal the arginine-free formulations described.

Inventors

  • 👤 Robert G. Kilbourn
  • 👤 Owen W. Griffith
  • 👤 Steven S. Gross

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-10-25 14:05
CPC Classifications
A; A61; A61K; A61K31/00; A61K31/70; A61K31/715; A61K31/33; A61K31/395; A61K31/41; A61K31/415

Claims Analysis

Total Claims: 11
Claim 1
Independent Claim 93 words
A method for treating hypotension due to septic shock or cytokine-induced hypotension by reducing blood arginine concentrations in an animal comprising: selecting a hypotensive animal having a systolic blood pressure of less than 100 mm Hg; administering to said animal an anti-hypotensive parenteral formulation comprising an essentially arginine-free mixture of amino acids in an amount sufficient to reduce blood arginine concentrations; obtaining periodic blood pressure measurements of the animal; and continuing administration of the anti-hypotensive parenteral formulation until a systolic blood pressure of greater than 100 mm Hg is detected in the animal.
Claim 2
Independent Claim 93 words
A method for treating hypotension due to septic shock or cytokine-induced hypotension by reducing blood arginine concentrations in an animal comprising: selecting a hypotensive animal having a systolic blood pressure of less than 100 mm Hg; administering to said animal an anti-hypotensive parenteral formulation comprising an essentially arginine-free mixture of amino acids in an amount sufficient to reduce blood arginine concentrations; obtaining periodic blood pressure measurements of the animal; and continuing administration of the anti-hypotensive parenteral formulation until a systolic blood pressure of greater than 100 mm Hg is detected in the animal.
Claim 3
Dependent Claim 77 words
The method of claim 1 wherein the anti-hypotensive parenteral formulation comprises: about 1-2 g/l ornithine; about 3-4 g/l isoleucine; about 4-6 g/l leucine; about 3-4 g/l lysine about 1-2 g/l methionine; about 1-2 g/l phenylalanine; about 2-3 g/l threonine; about 0.5-1.5 g/l tryptophan; about 3-4 g/l valine; about 4-5 g/l alanine; about 1-2 g/l histidine; about 3-4 g/l proline; about 1-2 g/l serine; about 0.25-0.75 g/l tyrosine; about 4-5 g/l glycine; and about 2-3 g/l aspartic acid.
Claim 4
Dependent Claim 20 words
The method of claim 1 wherein the anti-hypotensive parenteral formulation comprises about 1-2 g/l ornithine or about 1 g/l citrulline.
Claim 5
Independent Claim 157 words
A method for treating hypotension due to septic shock or cytokine-induced hypotension by reducing blood arginine concentrations in a patient comprising: selecting a patient with hypotension having an initial systolic blood pressure of less than 100 mm Hg; administering to the identified patient an arginine-free formulation comprising: about 3-4 g/l isoleucine; about 4-6 g/l leucine; about 3-4 g/l lysine; about 1-2 g/l methionine; about 1-2 g/l phenylalanine; about 2-3 g/l threonine; about 0.5-1.5 g/l tryptophan; about 3-4 g/l valine; about 4-5 g/l alanine; about 1-2 g/l histidine; about 3-4 g/l proline; about 1-2 g/l serine; about 0.25-0.75 g/l tyrosine; about 4-5 g/l glycine; and about 2-3 g/l aspartic acid, in an amount sufficient to reduce blood arginine concentrations; and making period systolic blood pressure measurements of the patient until a systolic blood pressure of at least 100 mm Hg is maintained for a period of time sufficient to establish a stable systolic blood pressure in the patient.
Claim 6
Independent Claim 157 words
A method for treating hypotension due to septic shock or cytokine-induced hypotension by reducing blood arginine concentrations in a patient comprising: selecting a patient with hypotension having an initial systolic blood pressure of less than 100 mm Hg; administering to the identified patient an arginine-free formulation comprising: about 3-4 g/l isoleucine; about 4-6 g/l leucine; about 3-4 g/l lysine; about 1-2 g/l methionine; about 1-2 g/l phenylalanine; about 2-3 g/l threonine; about 0.5-1.5 g/l tryptophan; about 3-4 g/l valine; about 4-5 g/l alanine; about 1-2 g/l histidine; about 3-4 g/l proline; about 1-2 g/l serine; about 0.25-0.75 g/l tyrosine; about 4-5 g/l glycine; and about 2-3 g/l aspartic acid, in an amount sufficient to reduce blood arginine concentrations; and making period systolic blood pressure measurements of the patient until a systolic blood pressure of at least 100 mm Hg is maintained for a period of time sufficient to establish a stable systolic blood pressure in the patient.
Claim 7
Dependent Claim 27 words
The method of claim 4 wherein stable systolic blood pressure is a systolic blood pressure of at least 100 mm Hg maintained for at least 24 hours.
Claim 8
Dependent Claim 13 words
The method of claim 4 wherein the anti-hypotension formulation includes ornithine and citrulline.
Claim 9
Dependent Claim 20 words
The method of claim 4 wherein the hypotension inhibiting formulation includes about 1 g/l citrulline and between 1-2 g/l ornithine.
Claim 10
Dependent Claim 18 words
The method of claim 4 wherein the hypotension is in response to tumor necrosis factor, interleukin-2, or interleukin-1.
Claim 11
Dependent Claim 15 words
The method of claim 1, 2, 3 or 4 wherein the patient is a human.

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3.5 Years (Year 4) 1997-02-14 1997-08-16 1998-02-15 $2000.00 Window Closed / Lapsed
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