Method for enhancing cellular bioenergy
First Claim
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1. A method for enhancing cellular bioenergy in an animal suffering from bioenergetic disease resulting from mitochondrially compromised cells, said method comprising administering to said animal uridine or a functional derivative or precursor thereof and a redox compound of Formula (I) having the structure:
- ##STR21## wherein R1, R2, R3 and R4 may be the same or different and R1 is H, C1 -C10 alkyl, C1 -C10 alkoxy, C2 -C10 alkenyl, C2 -C10 alkynyl, C3 -C10 cycloalkyl, C1 -C10 alkylthio, C1 -C10 haloalkyl, phenyl, phenoxy, or thiophenoxy, each of which may be either unsubstituted or substituted with a substituent from the group consisting of halogen, C1 -C6 alkyl, C1 -C6 alkoxy, alkylthio, amino, C1 -C6 haloalkyl and C1 -C5 haloalkoxy;
or ##STR22## wherein n and n1 are independently either 1 or 2;
n2 is 0 or 1;
n3 is either 1 or 2;
n4 is 1-40; and
whereinR5 and R6 may be the same or different and each is H, C1 -C10 alkyl, C1 -C10 alkoxy, C2 -C10 alkynyl, C3 -C10 cycloalkyl, C1 -C10 alkylthio, C1 -C10 haloalkyl, phenyl, phenoxy, or thiophenoxy, each of which may be either unsubstituted or substituted with a substituent selected from the group consisting of halogen, C1 -C6 alkyl, C1 -C6 alkoxy, alkylthio, amino, C1 -C6 haloalkyl and C1 -C5 haloalkoxy;
where R2, R3 and R4 each is selected from H, C1 -C10 alkyl, C1 -C10 alkoxy, C2 -C10 alkenyl, C2 -C10 alkynyl, C3 -C10 cycloalkyl, C1 -C10 alkylthio, C1 -C10 haloalkyl, phenyl, phenoxy, or thiophenoxy, each of which may be either unsubstituted or substituted with a substituent from the group consisting of halogen, C1 -C6 alkyl, C1 -C6 alkoxy, alkylthio, amino, C1 -C6 haloalkyl and C1 -C5 haloalkoxy; and
said compound being capable of replacing ferricyanide in the enablement of propagative aerobic growth of cultured ρ
°
cells of vertebrate origin in the absence of pyruvate.
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Abstract
The present invention relates generally to therapeutic compositions comprising one or more redox compounds. The therapeutic compositions of the present invention are useful in enhancing cellular ATP production thereby ameliorating the effects of reduced bioenergy capacity such as occurring during aging, systemic or vascular disease or in conjunction with chemical therapy. The present invention therefore contemplates a method for enhancing cellular ATP production in an animal, said method comprising administering to said animal, an effective amount of a redox compound for a time and under conditions sufficient to increase or otherwise elevate the activity and/or operation of a cellular oxidoreductase system in cells of said animal.
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Citations
25 Claims
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1. A method for enhancing cellular bioenergy in an animal suffering from bioenergetic disease resulting from mitochondrially compromised cells, said method comprising administering to said animal uridine or a functional derivative or precursor thereof and a redox compound of Formula (I) having the structure:
- ##STR21## wherein R1, R2, R3 and R4 may be the same or different and R1 is H, C1 -C10 alkyl, C1 -C10 alkoxy, C2 -C10 alkenyl, C2 -C10 alkynyl, C3 -C10 cycloalkyl, C1 -C10 alkylthio, C1 -C10 haloalkyl, phenyl, phenoxy, or thiophenoxy, each of which may be either unsubstituted or substituted with a substituent from the group consisting of halogen, C1 -C6 alkyl, C1 -C6 alkoxy, alkylthio, amino, C1 -C6 haloalkyl and C1 -C5 haloalkoxy;
or ##STR22## wherein n and n1 are independently either 1 or 2;n2 is 0 or 1; n3 is either 1 or 2; n4 is 1-40; and wherein R5 and R6 may be the same or different and each is H, C1 -C10 alkyl, C1 -C10 alkoxy, C2 -C10 alkynyl, C3 -C10 cycloalkyl, C1 -C10 alkylthio, C1 -C10 haloalkyl, phenyl, phenoxy, or thiophenoxy, each of which may be either unsubstituted or substituted with a substituent selected from the group consisting of halogen, C1 -C6 alkyl, C1 -C6 alkoxy, alkylthio, amino, C1 -C6 haloalkyl and C1 -C5 haloalkoxy; where R2, R3 and R4 each is selected from H, C1 -C10 alkyl, C1 -C10 alkoxy, C2 -C10 alkenyl, C2 -C10 alkynyl, C3 -C10 cycloalkyl, C1 -C10 alkylthio, C1 -C10 haloalkyl, phenyl, phenoxy, or thiophenoxy, each of which may be either unsubstituted or substituted with a substituent from the group consisting of halogen, C1 -C6 alkyl, C1 -C6 alkoxy, alkylthio, amino, C1 -C6 haloalkyl and C1 -C5 haloalkoxy; and said compound being capable of replacing ferricyanide in the enablement of propagative aerobic growth of cultured ρ
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cells of vertebrate origin in the absence of pyruvate. - View Dependent Claims (2, 3, 4, 8, 9, 10, 11, 17, 18, 19, 20)
- ##STR21## wherein R1, R2, R3 and R4 may be the same or different and R1 is H, C1 -C10 alkyl, C1 -C10 alkoxy, C2 -C10 alkenyl, C2 -C10 alkynyl, C3 -C10 cycloalkyl, C1 -C10 alkylthio, C1 -C10 haloalkyl, phenyl, phenoxy, or thiophenoxy, each of which may be either unsubstituted or substituted with a substituent from the group consisting of halogen, C1 -C6 alkyl, C1 -C6 alkoxy, alkylthio, amino, C1 -C6 haloalkyl and C1 -C5 haloalkoxy;
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5. A method for enhancing cellular bioenergy in an animal suffering from bioenergetic disease resulting from mitochondrially compromised cells, said method comprising administering to said animal uridine or a functional derivative or precursor thereof and a redox compound having the structure ##STR24## wherein R2 is H or methyl;
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R3 and R4 are the same or different and each is methyl or methoxy; and
##STR25## wherein n and n1 are independently 0, 1 or 2;
n2 is 0 or 1;
n3 is 0, 1, or 2; and
n4 is 1-40 andR6 is H and R5 is C1 -C10 alkyl, C2 -C10 alkynyl, C1 -C10 alkoxy or C2 -C10 alkenyl, said compound being capable of replacing ferricyanide in the enablement of propagative aerobic growth of cultured ρ
°
cells of vertebrate origin in the absence of pyruvate.
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6. A method for enhancing cellular bioenergy in an animal suffering from bioenergetic disease resulting from mitochrondrially compromised cells, said method comprising administration to said animal uridine or a functional derivative or precursor thereof and a redox compound having the structure:
- ##STR26## where n is 1 or 2;
n1 is 1 or 2;
n2 is 0 or 1;
n3 is 2 or 3;n4 is 1-40; and
n5 is 2 or 3,said compound being capable of replacing ferricyanide in the enablement of propagative aerobic growth of cultured ρ
°
cells of vertebrate origin in the absence of pyruvate.
- ##STR26## where n is 1 or 2;
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7. A method for enhancing cellular bioenergy in an animal suffering from bioenergetic disease resulting from mitochondrially compromised cells, said method comprising administrating to said animal uridine or a functional derivative or precursor thereof and a redox compound having the structure ##STR27## wherein n is 1 or 2;
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n1 is 1 or 2; n2 is 0 or 1; n3 is 2 or 3; n4 is 1-40; and n5 is 2 or 3, said compound being capable of replacing fericyanide in the enablement of propagative aerobic growth of cultured ρ
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cells of vertebrate origin in the absence of pyruvate.
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12. A pharmaceutical composition comprising a therapeutically effective amount of a redox compound of Formula (I) having the structure:
- ##STR28## wherein R1, R2, R3 and R4 may be the same or different and R1 is H, C1 -C10 alkyl, C1 -C10 alkoxy, C2 -C10 alkenyl, C2 -C10 alkynyl, C3 -C10 cycloalkyl, C1 -C10 alkylthio, C1 -C10 haloalkyl, phenyl, phenoxy, or thiophenoxy, each of which may be either unsubstituted or substituted with a substituent selected from the group consisting of halogen, C1 -C6 alkyl, C1 -C6 alkoxy, alkylthio, amino, C1 -C6 haloalkyl and C1 -C5 haloalkoxy;
or ##STR29## wherein n and n1 are independently either 1 or 2;n2 is 0 or 1; n3 is either 1 or 2; n4 is 1-40; and wherein R5 and R6 may be the same or different and each is H, C1 -C10 alkyl, C1 -C10 alkoxy, C2 -C10 alkynyl, C3 -C10 cycloalkyl, C1 -C10 alkylthio, C1 -C10 haloalkyl, phenyl, phenoxy, or thiophenoxy, each of which may be either unsubstituted or substituted with a substituent selected from the group consisting of halogen, C1 -C6 alkyl, C1 -C6 alkoxy, alkylthio, amino, C1 -C6 haloalkyl and C1 -C5 haloalkoxy; where R2, R3 and R4 each is selected from H, C1 -C10 alkyl, C1 -C10 alkoxy, C2 -C10 alkenyl, C2 -C10 alkynyl, C3 -C10 cycloalkyl, C1 -C10 alkylthio, C1 -C10 haloalkyl, phenyl, phenoxy, or thiophenoxy, each of which may be either unsubstituted or substituted with a substituent from the group consisting of halogen, C1 -C6 alkyl, C1 -C6 alkoxy, alkylthio, amino, C1 -C6 haloalkyl and C1 -C5 haloalkoxy, said compound being capable of replacing ferricyanide in the enablement of propagative aerobic growth of cultured ρ
°
cells of vertebrate origin in the absence of pyruvate; and
uridine or a functional derivative and/or precursor thereof, and one or more pharmaceutically acceptable carriers and/or diluents. - View Dependent Claims (13, 21, 22, 23, 24, 25)
- ##STR28## wherein R1, R2, R3 and R4 may be the same or different and R1 is H, C1 -C10 alkyl, C1 -C10 alkoxy, C2 -C10 alkenyl, C2 -C10 alkynyl, C3 -C10 cycloalkyl, C1 -C10 alkylthio, C1 -C10 haloalkyl, phenyl, phenoxy, or thiophenoxy, each of which may be either unsubstituted or substituted with a substituent selected from the group consisting of halogen, C1 -C6 alkyl, C1 -C6 alkoxy, alkylthio, amino, C1 -C6 haloalkyl and C1 -C5 haloalkoxy;
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14. A pharmaceutical composition comprising a therapeutically effective amount of a redox compound having the structure:
- ##STR31## wherein R2 is H or methyl;
R3 and R4 are the same or different and each is methyl or methoxy; and
##STR32## n and n1 are independently 1 or 2;
n2 is 0 or 1;n3 is 1 or 2; n4 is 1-40; R6 is H; and R8 is C1 -C10 alkyl, C2 -C10 alkynyl, C1 -C10 alkoxy or C2 -C10 alkenyl, and uridine or a functional derivative or a precursor thereof and one or more pharmaceutically acceptable carriers and/or diluents, whereby said redox compound is capable of replacing ferricyanide in the enablement of propagative aerobic growth of cultured ρ
°
cells of vertebrate origin in the absence of pyruvate.
- ##STR31## wherein R2 is H or methyl;
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15. A pharmaceutical composition comprising a therapeutically effective amount of a redox compound having the structure:
- ##STR33## where n is 1 or 2;
n1 is 1 or 2;
n2 is 0 or 1;
n3 is 2 or 3;
n4 is 1-40 and n5 is 2 or 3,and uridine or a functional derivative or a precursor thereof and one or more pharmaceutically acceptable carriers and/or diluents, whereby said redox compound is capable of replacing ferricyanide in the enablement of propagative aerobic growth of cultured ρ
°
cells of vertebrate origin in the absence of pyruvate.
- ##STR33## where n is 1 or 2;
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16. A pharmaceutical composition comprising a therapeutically effective amount of a redox compound having the structure:
- ##STR34## wherein n is 1 or 2;
n1 is 1 or 2;
n2 is 0 or 1;
n3 is 2 or 3;
n4 is 1-40; and
n5 is 2 or 3,and uridine or a functional derivative or a precursor thereof and one or more pharmaceutically acceptable carriers and/or diluents, whereby said redox compound is capable of replacing ferricyanide in the enablement of propagative aerobic growth of cultured ρ
°
cells of vertebrate origin in the absence of pyruvate.
- ##STR34## wherein n is 1 or 2;
Specification
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Current AssigneeCentre For Molecular Biology and Medicine
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Original AssigneeCentre For Molecular Biology and Medicine
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InventorsVaillant, Francois, Martinus, Ryan Dennis, Nagley, Phillip, Linnane, Anthony William
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Primary Examiner(s)Dees, Jose' G.
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Assistant Examiner(s)BADIO, BARBARA P
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Application NumberUS08/343,559Time in Patent Office1,695 DaysField of Search552/293, 514/293, 514/307, 514/296, 514/675, 514/690US Class Current514/690CPC Class CodesA61K 2300/00 Mixtures or combinations of...A61K 31/12 KetonesA61K 31/375 Ascorbic acid, i.e. vitamin...A61K 31/70 Carbohydrates; Sugars; Deri...A61P 31/12 AntiviralsA61P 43/00 Drugs for specific purposes...C07C 50/02 with monocyclic quinoid str...C07C 50/06 with unsaturation outside t...C07C 50/28 with monocyclic quinoid str...G01N 33/5014 for testing toxicityG01N 33/5088 of vertebrates
