US5028627A
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US
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Method of using arginine derivatives to inhibit systemic hypotension associated with nitric oxide production or endothelial derived relaxing factor
Assignee: Cornell Research Foundation Inc
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Filing: 1989-09-13
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Granted: 1991-07-02
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Expires: 2009-09-13
Abstract
Abstract A method for prophylaxis of treatment of an animal for systemic hypotension induced by internal nitrogen oxide production. The method involves administering a therapeutically effective amount of certain arginine derivatives to inhibit nitrogen oxide formation from arginine. Preferaby N G -substituted arginine or an N G ,N G -disubstituted arginine (having at least one hydrogen on a terminal guanidino amino group replaced by another atomic species) is administered to an animal possibly developing or already having induced systemic hypotension. The arginine derivatives are preferably of the L configuration and include pharmaceutically acceptable addition salts. Prophylaxis or treatment or systemic hypotension in a patient which has been induced by chemotherapeutic treatment with biologic response modifiers such as tumor necrosis factor or interleukin-2 may be accomplished. Treatment of an animal for systemic hypotension induced by endotoxin, i.e., septic shock may also be accomplished by treatment with the arginine derivatives.
Inventors
- 👤 Robert G. Kilbourn
- 👤 Steven Gross
- 👤 Roberto Levi
- 👤 Owen W. Griffith
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-25 14:36
CPC Classifications
A; A61; A61K; A61K31/00; A61K31/185; A61K31/19; A61K31/195; A61K31/197; A61K31/198; A61K31/21; A61K31/215; A61K31/22; A61K31/223; A61P; A61P43/00; A61P9/00; A61P9/02; A61P9/12
Claims Analysis
Total Claims: 74
Claim 1
Independent Claim
87 words
A method for prophylaxis or treatment of an animal for systemic hypotension induced by gamma-interferon, tumor necrosis factor, interleukin-1 or interleukin-2 said method involving intravascularly administering a therapeutically effective amount of an N G -substituted arginine or an N G ,N G -disubstituted arginine to an animal possibly developing or having such induced systemic hypotension wherein the N G -substituted or N G ,N G -disubstituted arginine has a nitro, amino, lower alkyl, lower hydroxyalkyl or lower alkenyl substituent replacing a hydrogen of a guanidino amino group.
Claim 2
Independent Claim
87 words
A method for prophylaxis or treatment of an animal for systemic hypotension induced by gamma-interferon, tumor necrosis factor, interleukin-1 or interleukin-2 said method involving intravascularly administering a therapeutically effective amount of an N G -substituted arginine or an N G ,N G -disubstituted arginine to an animal possibly developing or having such induced systemic hypotension wherein the N G -substituted or N G ,N G -disubstituted arginine has a nitro, amino, lower alkyl, lower hydroxyalkyl or lower alkenyl substituent replacing a hydrogen of a guanidino amino group.
Claim 3
Independent Claim
79 words
A method for prophylaxis or treatment of systemic hypotension in a patient induced by chemotherapeutic treatment with tumor necrosis factor or interleukin-2, said method involving intravascularly administering to said patient a therapeutically effective amount of N G -substituted arginine or an N G ,N G -disubstituted arginine to a patient wherein the N G -substituted or N G ,N G -disubstituted arginine has a nitro, amino, alkyl, hydroxyalkyl, or alkenyl substituent replacing a hydrogen of a guanidino amino group.
Claim 4
Independent Claim
79 words
A method for prophylaxis or treatment of systemic hypotension in a patient induced by chemotherapeutic treatment with tumor necrosis factor or interleukin-2, said method involving intravascularly administering to said patient a therapeutically effective amount of N G -substituted arginine or an N G ,N G -disubstituted arginine to a patient wherein the N G -substituted or N G ,N G -disubstituted arginine has a nitro, amino, alkyl, hydroxyalkyl, or alkenyl substituent replacing a hydrogen of a guanidino amino group.
Claim 5
Independent Claim
79 words
A method for treatment of an animal for systemic hypotension induced by exposure to endotoxin, said method involving intravascularly administering to said animal a therapeutically effective amount of N G -substituted arginine or N G ,N G -disubstituted arginine to an animal having such induced systemic hypotension, wherein the N G -substituted or N G ,N G -disubstituted arginine has a nitro, amino, lower alkyl, lower hydroxyalkyl, or lower alkenyl substituent replacing a hydrogen of a guanidino amino group.
Claim 6
Independent Claim
79 words
A method for treatment of an animal for systemic hypotension induced by exposure to endotoxin, said method involving intravascularly administering to said animal a therapeutically effective amount of N G -substituted arginine or N G ,N G -disubstituted arginine to an animal having such induced systemic hypotension, wherein the N G -substituted or N G ,N G -disubstituted arginine has a nitro, amino, lower alkyl, lower hydroxyalkyl, or lower alkenyl substituent replacing a hydrogen of a guanidino amino group.
Claim 7
Dependent Claim
33 words
The method of claim 1, 2, or 3 wherein the N G -substituted arginine is a lower N G -aminoarginine, N G -nitroarginine, N G -methylarginine, N G -ethylarginine, or N G -propylarginine.
Claim 8
Dependent Claim
19 words
The method of claim 1, 2 or 3 wherein the N G substituted arginine is N G alkyl arginine.
Claim 9
Dependent Claim
34 words
The method of claim 1, 2 or 3 wherein the N G -substituted arginine is N G -substituted L-arginine and the N G ,N G -disubstituted arginine is N G ,N G -disubstituted L-arginine.
Claim 10
Dependent Claim
30 words
The method of claim 1, 2 or 3 wherein said therapeutically effective amount of substituted or disubstituted arginine inhibits production in the animal or patient of nitric oxide from arginine.
Claim 11
Independent Claim
48 words
A method for prophylaxis or treatment of an animal for systemic hypotension caused by induced production of nitric oxide, said method involving administering a therapeutically effective amount of an arginine antagonist inhibiting production of said nitric oxide from arginine, to an animal possibly developing or having systemic hypotension.
Claim 12
Independent Claim
48 words
A method for prophylaxis or treatment of an animal for systemic hypotension caused by induced production of nitric oxide, said method involving administering a therapeutically effective amount of an arginine antagonist inhibiting production of said nitric oxide from arginine, to an animal possibly developing or having systemic hypotension.
Claim 13
Independent Claim
56 words
A method for prophylaxis or treatment of an animal for systemic hypotension caused by nitric oxide production induced by gamma-interferon, tumor necrosis factor, interleukin-1, or interleukin-2, said method involving intravascularly administering a therapeutically effective amount of an arginine antagonist inhibiting production of nitric oxide from arginine, to an animal possibly developing or having such systemic hypotension.
Claim 14
Independent Claim
56 words
A method for prophylaxis or treatment of an animal for systemic hypotension caused by nitric oxide production induced by gamma-interferon, tumor necrosis factor, interleukin-1, or interleukin-2, said method involving intravascularly administering a therapeutically effective amount of an arginine antagonist inhibiting production of nitric oxide from arginine, to an animal possibly developing or having such systemic hypotension.
Claim 15
Independent Claim
48 words
A method for treatment of an animal for systemic hypotension caused by nitric oxide production induced by exposure to endotoxin, said method involving intravascularly administering a therapeutically effective amount of an arginine antagonist inhibiting production of said nitric oxide from arginine, to an animal having such systemic hypotension.
Claim 16
Independent Claim
48 words
A method for treatment of an animal for systemic hypotension caused by nitric oxide production induced by exposure to endotoxin, said method involving intravascularly administering a therapeutically effective amount of an arginine antagonist inhibiting production of said nitric oxide from arginine, to an animal having such systemic hypotension.
Claim 17
Independent Claim
59 words
A method for prophylaxis or treatment of an animal for systemic hypotension induced by gamma-interferon, tumor necrosis factor, interleukin-1 or interleukin-2, said method involving intravascularly administering a therapeutically effective amount of lower N G -alkylarginine lower N G ,N G -dialkylarginine, N G -aminoarginine or N G -nitroarginine to an animal possibly developing or having such induced systemic hypotension.
Claim 18
Independent Claim
59 words
A method for prophylaxis or treatment of an animal for systemic hypotension induced by gamma-interferon, tumor necrosis factor, interleukin-1 or interleukin-2, said method involving intravascularly administering a therapeutically effective amount of lower N G -alkylarginine lower N G ,N G -dialkylarginine, N G -aminoarginine or N G -nitroarginine to an animal possibly developing or having such induced systemic hypotension.
Claim 19
Dependent Claim
30 words
The method of claim 11 wherein the N G -alkylarginine or N G ,N G -dialkylarginine has an alkyl substituent selected from the group consisting of methyl, ethyl, and propyl.
Claim 20
Independent Claim
76 words
A method for prophylaxis or treatment of an animal for systemic hypotension induced by gamma-interferon, tumor necrosis factor, interleukin-1, or interleukin-2, said method involving intravascularly administering a therapeutically effective amount of N G -substituted arginine or a N G ,N G -disubstituted arginine wherein the N G -substituted arginine or N G ,N G -disubstituted arginine has a lower hydroxyalkyl, a lower carboxyalkyl or a lower aminoalkyl substituent replacing a hydrogen of a guanidino amino group.
Claim 21
Independent Claim
76 words
A method for prophylaxis or treatment of an animal for systemic hypotension induced by gamma-interferon, tumor necrosis factor, interleukin-1, or interleukin-2, said method involving intravascularly administering a therapeutically effective amount of N G -substituted arginine or a N G ,N G -disubstituted arginine wherein the N G -substituted arginine or N G ,N G -disubstituted arginine has a lower hydroxyalkyl, a lower carboxyalkyl or a lower aminoalkyl substituent replacing a hydrogen of a guanidino amino group.
Claim 22
Independent Claim
49 words
A method for treatment of an animal for systemic hypotension induced by exposure to endotoxin, said method involving administering a therapeutically effective amount of lower N G -alkylarginine lower N G ,N G -dialkylarginine, N G -aminoarginine or N G -nitroarginine to an animal having such induced systemic hypotension.
Claim 23
Independent Claim
49 words
A method for treatment of an animal for systemic hypotension induced by exposure to endotoxin, said method involving administering a therapeutically effective amount of lower N G -alkylarginine lower N G ,N G -dialkylarginine, N G -aminoarginine or N G -nitroarginine to an animal having such induced systemic hypotension.
Claim 24
Independent Claim
61 words
A method for prophylaxis or treatment of systemic hypotension in a patient undergoing anticancer chemotherapy with tumor necrosis factor or interleukin-2, said method involving intravascularly administering a therapeutically effective amount of lower N G -alkyl-arginine, N G ,N G -dialkylarginine, lower N G -aminoarginine or N G -nitroarginine to said patient having or possible developing systemic hypotension induced by such chemotherapy.
Claim 25
Independent Claim
61 words
A method for prophylaxis or treatment of systemic hypotension in a patient undergoing anticancer chemotherapy with tumor necrosis factor or interleukin-2, said method involving intravascularly administering a therapeutically effective amount of lower N G -alkyl-arginine, N G ,N G -dialkylarginine, lower N G -aminoarginine or N G -nitroarginine to said patient having or possible developing systemic hypotension induced by such chemotherapy.
Claim 26
Independent Claim
50 words
A method for prophylaxis or treatment of a patient for systemic hypotension caused by induced production of nitric oxide, said method involving intravascularly administering a therapeutically effective amount of an arginine antagonist inhibiting production of said nitric oxide from arginine, to a patient possibly developing or having such systemic hypotension.
Claim 27
Independent Claim
50 words
A method for prophylaxis or treatment of a patient for systemic hypotension caused by induced production of nitric oxide, said method involving intravascularly administering a therapeutically effective amount of an arginine antagonist inhibiting production of said nitric oxide from arginine, to a patient possibly developing or having such systemic hypotension.
Claim 28
Independent Claim
61 words
A method for prophylaxis or treatment of a patient for systemic hypotension induced by therapy with tumor necrosis factor, gamma interferon, interleukin-1or interleukin-2, said method involving intravascularly administering a therapeutically effective amount of lower N G -alkylarginine lower N G ,N G -dialkylarginine, N G -aminoarginine or N G -nitroarginine to a patient possibly developing or having such induced systemic hypotension.
Claim 29
Independent Claim
61 words
A method for prophylaxis or treatment of a patient for systemic hypotension induced by therapy with tumor necrosis factor, gamma interferon, interleukin-1or interleukin-2, said method involving intravascularly administering a therapeutically effective amount of lower N G -alkylarginine lower N G ,N G -dialkylarginine, N G -aminoarginine or N G -nitroarginine to a patient possibly developing or having such induced systemic hypotension.
Claim 30
Independent Claim
49 words
A method for treatment of a patient for systemic hypotension induced by exposure to endotoxin, said method involving intravascularly administering a therapeutically effective amount of lower N G -alkylarginine, lower N G ,N G -dialkylarginine, N G -aminoarginine or N G -nitroarginine to a patient having such systemic hypotension.
Claim 31
Independent Claim
49 words
A method for treatment of a patient for systemic hypotension induced by exposure to endotoxin, said method involving intravascularly administering a therapeutically effective amount of lower N G -alkylarginine, lower N G ,N G -dialkylarginine, N G -aminoarginine or N G -nitroarginine to a patient having such systemic hypotension.
Claim 32
Independent Claim
64 words
A method for prophylaxis or treatment of a patient for systemic hypotension caused by tumor necrosis factor, gamma-interferon, interleukin-1, or interleukin-2, and resultant production of nitric oxide, said method involving intravascularly administering a therapeutically effective amount of lower N G -alkylarginine, lower N G ,N G -dialkylarginine, N G -aminoarginine or N G -nitroarginine to a patient possibly developing or having such systemic hypotension.
Claim 33
Independent Claim
64 words
A method for prophylaxis or treatment of a patient for systemic hypotension caused by tumor necrosis factor, gamma-interferon, interleukin-1, or interleukin-2, and resultant production of nitric oxide, said method involving intravascularly administering a therapeutically effective amount of lower N G -alkylarginine, lower N G ,N G -dialkylarginine, N G -aminoarginine or N G -nitroarginine to a patient possibly developing or having such systemic hypotension.
Claim 34
Independent Claim
58 words
A method for treatment of a patient for systemic hypotension caused by exposure of said patient to endotoxin, and resultant production of nitric oxide, said method involving intravascularly administering a therapeutically effective amount of lower N G -alkylarginine, lower N G N G -dialkylarginine, N G -aminoarginine or N G -nitroarginine to a patient having such systemic hypotension.
Claim 35
Independent Claim
58 words
A method for treatment of a patient for systemic hypotension caused by exposure of said patient to endotoxin, and resultant production of nitric oxide, said method involving intravascularly administering a therapeutically effective amount of lower N G -alkylarginine, lower N G N G -dialkylarginine, N G -aminoarginine or N G -nitroarginine to a patient having such systemic hypotension.
Claim 36
Independent Claim
56 words
A method for prophylaxis or treatment of a patient for systemic hypotension caused by nitric oxide production induced by tumor necrosis factor, gamma-interferon, interleukin-1, or interleukin-2, said method involving intravascularly administering a therapeutically effective amount of an arginine antagonist inhibiting production of said nitric oxide from arginine, to a patient possibly developing or having systemic hypotension.
Claim 37
Independent Claim
56 words
A method for prophylaxis or treatment of a patient for systemic hypotension caused by nitric oxide production induced by tumor necrosis factor, gamma-interferon, interleukin-1, or interleukin-2, said method involving intravascularly administering a therapeutically effective amount of an arginine antagonist inhibiting production of said nitric oxide from arginine, to a patient possibly developing or having systemic hypotension.
Claim 38
Independent Claim
48 words
A method for treatment of a patient for systemic hypotension caused by nitric oxide production induced by exposure to endotoxin, said method involving intravascularly administering a therapeutically effective amount of an arginine antagonist inhibiting production of said nitric oxide from arginine, to a patient having such systemic hypotension.
Claim 39
Independent Claim
48 words
A method for treatment of a patient for systemic hypotension caused by nitric oxide production induced by exposure to endotoxin, said method involving intravascularly administering a therapeutically effective amount of an arginine antagonist inhibiting production of said nitric oxide from arginine, to a patient having such systemic hypotension.
Claim 40
Independent Claim
54 words
A method for prophylaxis or treatment of a patient for systemic hypotension caused by nitric oxide production induced by therapy with tumor necrosis factor, said method involving intravascularly administering a therapeutically effective amount of an arginine antagonist inhibiting production of said nitric oxide from arginine, to a patient possibly developing or having systemic hypotension.
Claim 41
Independent Claim
54 words
A method for prophylaxis or treatment of a patient for systemic hypotension caused by nitric oxide production induced by therapy with tumor necrosis factor, said method involving intravascularly administering a therapeutically effective amount of an arginine antagonist inhibiting production of said nitric oxide from arginine, to a patient possibly developing or having systemic hypotension.
Claim 42
Independent Claim
82 words
A method for prophylaxis or treatment of a patient for systemic hypotension caused by nitric oxide production induced by gamma-interferon, tumor necrosis factor, interleukin-1, or interleukin-2, said method involving intravascularly administering a therapeutically effective amount of an arginine antagonist inhibiting production of said nitric oxide from arginine, to an animal possibly developing or having such systemic hypotension, said arginine antagonist being arginine with an N G substituent selected from the group consisting of amino, nitro, lower alkyl, lower hydroxyalkyl, or lower alkenyl.
Claim 43
Independent Claim
82 words
A method for prophylaxis or treatment of a patient for systemic hypotension caused by nitric oxide production induced by gamma-interferon, tumor necrosis factor, interleukin-1, or interleukin-2, said method involving intravascularly administering a therapeutically effective amount of an arginine antagonist inhibiting production of said nitric oxide from arginine, to an animal possibly developing or having such systemic hypotension, said arginine antagonist being arginine with an N G substituent selected from the group consisting of amino, nitro, lower alkyl, lower hydroxyalkyl, or lower alkenyl.
Claim 44
Independent Claim
73 words
A method for treatment of an animal for systemic hypotension caused by nitric oxide production induced by exposure to endotoxin, said method involving intravascularly administering a therapeutically effective amount of an arginine antagonist inhibiting production of said nitric oxide from arginine, to an animal having such systemic hypotension, said arginine antagonist being arginine with an N G substituent selected from the group consisting of amino, nitro, lower alkyl, lower hydroxyalkyl, or lower alkenyl.
Claim 45
Independent Claim
73 words
A method for treatment of an animal for systemic hypotension caused by nitric oxide production induced by exposure to endotoxin, said method involving intravascularly administering a therapeutically effective amount of an arginine antagonist inhibiting production of said nitric oxide from arginine, to an animal having such systemic hypotension, said arginine antagonist being arginine with an N G substituent selected from the group consisting of amino, nitro, lower alkyl, lower hydroxyalkyl, or lower alkenyl.
Claim 46
Dependent Claim
30 words
The method of claim 1, 2, 3, 8, 10, 11, 19 or 25 wherein the therapeutically effective amount is an amount sufficient to inhibit production of nitric oxide from arginine.
Claim 47
Independent Claim
51 words
A method for prophylaxis or treatment of an animal for systemic hypotension induced by gamma-interferon, tumor necrosis factor, interleukin-1 or interleukin-2 said method involving intravascularly administering a therapeutically effective amount of N G -methylarginine or N G ,N G -dimethylarginine to an animal possibly developing or having such induced systemic hypotension.
Claim 48
Independent Claim
51 words
A method for prophylaxis or treatment of an animal for systemic hypotension induced by gamma-interferon, tumor necrosis factor, interleukin-1 or interleukin-2 said method involving intravascularly administering a therapeutically effective amount of N G -methylarginine or N G ,N G -dimethylarginine to an animal possibly developing or having such induced systemic hypotension.
Claim 49
Independent Claim
59 words
A method for prophylaxis or treatment of an animal for systemic hypotension caused by a production of nitric oxide induced by therapy with gamma-interferon, tumor necrosis factor, interleukin-1 or interleukin-2, said method involving intravascularly administering a therapeutically effective amount of N G -methylarginine or N G ,N G -dimethyl-arginine to an animal possibly developing or having such systemic hypotension.
Claim 50
Independent Claim
59 words
A method for prophylaxis or treatment of an animal for systemic hypotension caused by a production of nitric oxide induced by therapy with gamma-interferon, tumor necrosis factor, interleukin-1 or interleukin-2, said method involving intravascularly administering a therapeutically effective amount of N G -methylarginine or N G ,N G -dimethyl-arginine to an animal possibly developing or having such systemic hypotension.
Claim 51
Independent Claim
53 words
A method for prophylaxis or treatment of an animal for systemic hypotension induced by therapy with gamma-interferon, tumor necrosis factor, interleukin-1, or interleukin-2, said method involving intravascularly administering a therapeutically effective amount of N G -methylarginine or N G ,N G -dimethylarginine to an animal possibly developing or having such induced systemic hypotension.
Claim 52
Independent Claim
53 words
A method for prophylaxis or treatment of an animal for systemic hypotension induced by therapy with gamma-interferon, tumor necrosis factor, interleukin-1, or interleukin-2, said method involving intravascularly administering a therapeutically effective amount of N G -methylarginine or N G ,N G -dimethylarginine to an animal possibly developing or having such induced systemic hypotension.
Claim 53
Independent Claim
43 words
A method for treatment of an animal for systemic hypotension induced by exposure to endotoxin, said method involving intravascularly administering a therapeutically effective amount of N G -methylarginine or N G , N G -dimethylarginine to an animal having such induced systemic hypotension.
Claim 54
Independent Claim
43 words
A method for treatment of an animal for systemic hypotension induced by exposure to endotoxin, said method involving intravascularly administering a therapeutically effective amount of N G -methylarginine or N G , N G -dimethylarginine to an animal having such induced systemic hypotension.
Claim 55
Independent Claim
72 words
A method for prophylaxis or treatment of an animal for systemic hypotension caused by production of nitric oxide induced by therapy of said animal with gamma-interferon, tumor necrosis factor, interleukin-1or interleukin-2, said method involving intravascularly administering a therapeutically effective amount of N G -methylarginine or N G ,N G -dimethylarginine to an animal possibly developing or having such systemic hypotension, said therapeutically effective amount reducing or preventing production of said nitric oxide.
Claim 56
Independent Claim
72 words
A method for prophylaxis or treatment of an animal for systemic hypotension caused by production of nitric oxide induced by therapy of said animal with gamma-interferon, tumor necrosis factor, interleukin-1or interleukin-2, said method involving intravascularly administering a therapeutically effective amount of N G -methylarginine or N G ,N G -dimethylarginine to an animal possibly developing or having such systemic hypotension, said therapeutically effective amount reducing or preventing production of said nitric oxide.
Claim 57
Independent Claim
62 words
A method for treating of an animal for systemic hypotension caused by production of nitric oxide induced by exposure of said animal to endotoxin, said method involving intravascularly administering a therapeutically effective amount of N G -methylarginine or N G N G dimethylarginine to an animal having such systemic hypotension, said therapeutically effective amount reducing or preventing production of said nitric oxide.
Claim 58
Independent Claim
62 words
A method for treating of an animal for systemic hypotension caused by production of nitric oxide induced by exposure of said animal to endotoxin, said method involving intravascularly administering a therapeutically effective amount of N G -methylarginine or N G N G dimethylarginine to an animal having such systemic hypotension, said therapeutically effective amount reducing or preventing production of said nitric oxide.
Claim 59
Independent Claim
21 words
The method of any of claims 27-32 wherein the therapeutically effective amount is between about 0.1 mg/kg and about 100 mg/kg.
Claim 60
Independent Claim
30 words
The method of any of claims 27-32 wherein the N G -methylarginine or N G ,N G -dimethylarginine are N G -methyl L-arginine or N G ,N G -dimethyl L-arginine.
Claim 61
Independent Claim
81 words
A method for prophylaxis or treatment of systemic hypotension in a patient induced by chemotherapeutic treatment with tumor necrosis factor or interleukin-2, said method involving administering to said patient a therapeutically effective amount of N G -substituted arginine or an N G ,N G -disubstituted arginine to a patient wherein the N G -substituted or N G ,N G -disubstituted arginine has a nitro, amino, lower alkyl, lower hydroxyalkyl or lower alkenyl substituent, replacing a hydrogen or a guanidino amino group.
Claim 62
Independent Claim
81 words
A method for prophylaxis or treatment of systemic hypotension in a patient induced by chemotherapeutic treatment with tumor necrosis factor or interleukin-2, said method involving administering to said patient a therapeutically effective amount of N G -substituted arginine or an N G ,N G -disubstituted arginine to a patient wherein the N G -substituted or N G ,N G -disubstituted arginine has a nitro, amino, lower alkyl, lower hydroxyalkyl or lower alkenyl substituent, replacing a hydrogen or a guanidino amino group.
Claim 63
Independent Claim
79 words
A method for treatment of an animal for systemic hypotension induced by exposure to endotoxin, said method involving administering to said animal a therapeutically effective amount of N G -substituted arginine or N G , N G -disubstituted arginine to an animal having such induced systemic hypotension wherein the N G -substituted or N G ,N G -disubstituted arginine has a nitro, amino, lower alkyl, lower hydroxyalkyl, or lower alkenyl substituent replacing a hydrogen of a guanidino amino group.
Claim 64
Independent Claim
79 words
A method for treatment of an animal for systemic hypotension induced by exposure to endotoxin, said method involving administering to said animal a therapeutically effective amount of N G -substituted arginine or N G , N G -disubstituted arginine to an animal having such induced systemic hypotension wherein the N G -substituted or N G ,N G -disubstituted arginine has a nitro, amino, lower alkyl, lower hydroxyalkyl, or lower alkenyl substituent replacing a hydrogen of a guanidino amino group.
Claim 65
Independent Claim
58 words
A method for prophylaxis or treatment of an animal for systemic hypotension caused by nitric oxide production induced by therapy with gamma-interferon, tumor necrosis factor, interleukin-1, or interleukin-2, said method involving administering a therapeutically effective amount of an arginine antagonist inhibiting production of said nitric oxide from arginine, to an animal possibly developing or having such systemic hypotension.
Claim 66
Independent Claim
58 words
A method for prophylaxis or treatment of an animal for systemic hypotension caused by nitric oxide production induced by therapy with gamma-interferon, tumor necrosis factor, interleukin-1, or interleukin-2, said method involving administering a therapeutically effective amount of an arginine antagonist inhibiting production of said nitric oxide from arginine, to an animal possibly developing or having such systemic hypotension.
Claim 67
Independent Claim
47 words
A method for treatment of an animal for systemic hypotension caused by nitric oxide production induced by exposure to endotoxin, said method involving administering a therapeutically effective amount of an arginine antagonist inhibiting production of said nitric oxide from arginine, to an animal having such systemic hypotension.
Claim 68
Independent Claim
47 words
A method for treatment of an animal for systemic hypotension caused by nitric oxide production induced by exposure to endotoxin, said method involving administering a therapeutically effective amount of an arginine antagonist inhibiting production of said nitric oxide from arginine, to an animal having such systemic hypotension.
Claim 69
Independent Claim
55 words
A method for prophylaxis or treatment of an animal for systemic hypotension induced by therapy with gamma-interferon, tumor necrosis factor, interleukin-1 or interleukin-2, said method involving administering a therapeutically effective amount of lower N G -alkylarginine lower or N G , N G -dialkylarginine to an animal possibly developing or having such induced systemic hypotension.
Claim 70
Independent Claim
55 words
A method for prophylaxis or treatment of an animal for systemic hypotension induced by therapy with gamma-interferon, tumor necrosis factor, interleukin-1 or interleukin-2, said method involving administering a therapeutically effective amount of lower N G -alkylarginine lower or N G , N G -dialkylarginine to an animal possibly developing or having such induced systemic hypotension.
Claim 71
Dependent Claim
14 words
The method of claim 35, 36, 37 or 38 wherein the administering is parenteral.
Claim 72
Dependent Claim
10 words
The method of claim 40 wherein the administering is intraperitoneal.
Claim 73
Dependent Claim
14 words
The method of claim 35, 36, 37 or 38 wherein the administering is enteral.
Claim 74
Dependent Claim
17 words
The method of claim 35, 36, 37 or 38 wherein the administering is topical, intradermal or intramuscular.
References Cited (Backward Citations)
US4282217A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1994-07-01 | 1994-12-31 | 1995-07-02 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1998-07-01 | 1998-12-31 | 1999-07-02 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2002-07-01 | 2002-12-31 | 2003-07-02 | $7700.00 | Window Closed / Lapsed |