What is claimed is:
1. A method for inhibiting body odors in a subject comprising administering to said subject cosmeticspersonal care products into which are incorporated a complexing agent having the formula
213
wherein,
p and q are independently integers of from 2 to 3;
r is an integer of from 1 to 4;
R2, R3, and R4 are each independently selected from the group consisting of H, alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenoxy, alkenylthio, aryloxy, arylthio, alkyl interrupted by oxa, alkenyl interrupted by oxa, alkyl interrupted by thia, alkenyl interrupted by thia, aryloxyalkyl, alkoxyaryl, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, hydroxyarylalkyl, and halogen-substituted versions thereof;
R1 is a member selected from the group consisting of R2, R3, R4, and radicals of the formula:
214
wherein,
R41, R42, and R43 are each independently selected from the group consisting of H, alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenoxy, alkenylthio, aryloxy, arylthio, alkyl interrupted by oxa, alkenyl interrupted by oxa, alkyl interrupted by thia, alkenyl interrupted by thia, aryloxyalkyl, alkoxyaryl, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, hydroxyarylalkyl, and halogen-substituted versions thereof;
R44 is a member selected from the group consisting of H, hydroxy, amino, alkyl interrupted by oxa, alkoxy, aryl, aryloxyalkyl, alkoxyaryl, alkoxyaryl, and halogen-substituted versions thereof;
n is zero or 1; and
X is a member selected from the group consisting of alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenoxy, alkenylthio, aryloxy, arylthio, alkyl interrupted by oxa, alkenyl interrupted by oxa, alkyl interrupted by thia, alkenyl interrupted by thia, aryloxyalkyl, alkoxyaryl, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, hydroxyarylalkyl, halogen-substituted versions thereof, and radicals selected form the group consisting of:
215
wherein,
R41, R42, R43 and R44 are each independently as defined above;
R46 and R47 are each independently selected from the group consisting of H, alkyl and aryl, or taken together form a ring structure;
R48 and R49 are each independently selected from the group consisting of H, alkyl, aryl, alkoxy, alkyl interrupted by oxa, aryloxyalkyl, alkoxyaryl, and halogen-substituted versions thereof;
R50, R51 and R52 are each independently selected from the group consisting of H, alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenyloxy, allkenylthio, aryloxy, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylakyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, and hydroxyarylalkyl; and
m is an integer of from 1 to 3
and wherein, optionally, any two of R1, R2, R3 and R4 are combined to form a ring structure;
and dimers of Formula I, said dimers being formed by the covalent attachment of two complexing agents of Formula I through a linking group having from 1 to 6 carbon atoms; and physiological salts thereof;
with the proviso that the molecular weight of said complexing agent does not exceed 2000.
2. A method of inhibiting tooth decay, gum disease and periodontal disease in a subject, comprising administering to said subject an oral care product incorporating a complexing agent having the formula:
216
wherein,
p and q are independently either 2 or 3;
r is an integer of from 1 to 4;
R2, R3, and R4 are each independently selected from the group consisting of H, alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenoxy, alkenylthio, aryloxy, arylthio, alkyl interrupted by oxa, alkenyl interrupted by oxa, alkyl interrupted by thia, alkenyl interrupted by thia, aryloxyalkyl, alkoxyaryl, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, hydroxyarylalkyl, and halogen-substituted versions thereof;
R1 is a member selected from the group consisting of R2, R3, R4, and radicals of the formula:
217
wherein,
R41, R42, and R43 are each independently selected from the group consisting of H, alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenoxy, alkenylthio, aryloxy, arylthio, alkyl interrupted by oxa, alkenyl interrupted by oxa, alkyl interrupted by thia, alkenyl interrupted by thia, aryloxyalkyl, alkoxyaryl, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, hydroxyarylalkyl, and halogen-substituted versions thereof;
R44 is a member selected from the group consisting of H, hydroxy, amino, alkyl interrupted by oxa, alkoxy, aryl, aryloxyalkyl, alkoxyaryl, alkoxyaryl, and halogen-substituted versions thereof;
n is zero or 1; and
X is a member selected from the group consisting of alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenoxy, alkenylthio, aryloxy, arylthio, alkyl interrupted by oxa, alkenyl interrupted by oxa, alkyl interrupted by thia, alkenyl interrupted by thia, aryloxyalkyl, alkoxyaryl, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, hydroxyarylalkyl, halogen-substituted versions thereof, and radicals selected form the group consisting of:
218
wherein,
R41, R42, R43 and R44 are each independently as defined above;
R46 and R47 are each independently selected from the group consisting of H, alkyl and aryl, or taken together form a ring structure;
R48 and R49 are each independently selected from the group consisting of H, alkyl, aryl, alkoxy, alkyl interrupted by oxa, aryloxyalkyl, alkoxyaryl, and halogen-substituted versions thereof;
R50, R51 and R52 are each independently selected from the group consisting of H, alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenyloxy, alkenylthio, aryloxy, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylakyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, and hydroxyarylalkyl; and
m is an integer of from 1 to 3
and wherein, optionally, any two of R1, R2, R3 and R4 are combined to form a ring structure;
and dimers of Formula I, said dimers being formed by the covalent attachment of two complexing agents of Formula I through a linking group having from 1 to 6 carbon atoms; and physiological salts thereof;
with the proviso that the molecular weight of said complexing agent does not exceed 2000.
3. A method of inhibiting oxidative damage to skin and skin appendages in a subject, comprising administering to said subject a skin and skin appendage care product incorporating a complexing agent having the formula:
219
wherein,
p and q are independently either 2 or 3;
r is an integer of from 1 to 4;
R2, R3, and R4 are each independently selected from the group consisting of H, alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenoxy, alkenylthio, aryloxy, arylthio, alkyl interrupted by oxa, alkenyl interrupted by oxa, alkyl interrupted by thia, alkenyl interrupted by thia, aryloxyalkyl, alkoxyaryl, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, hydroxyarylalkyl, and halogen-substituted versions thereof;
R1 is a member selected from the group consisting of R2, R3, R4, and radicals of the formula:
220
wherein,
R41, R42, and R43 are each independently selected from the group consisting of H, alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenoxy, alkenylthio, aryloxy, arylthio, alkyl interrupted by oxa, alkenyl interrupted by oxa, alkyl interrupted by thia, alkenyl interrupted by thia, aryloxyalkyl, alkoxyaryl, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, hydroxyarylalkyl, and halogen-substituted versions thereof;
R44 is a member selected from the group consisting of H, hydroxy, amino, alkyl interrupted by oxa, alkoxy, aryl, aryloxyalkyl, alkoxyaryl, alkoxyaryl, and halogen-substituted versions thereof;
n is zero or 1; and
X is a member selected from the group consisting of alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenoxy, alkenylthio, aryloxy, arylthio, alkyl interrupted by oxa, alkenyl interrupted by oxa, alkyl interrupted by thia, alkenyl interrupted by thia, aryloxyalkyl, alkoxyaryl, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, hydroxyarylalkyl, halogen-substituted versions thereof, and radicals selected form the group consisting of:
221
wherein,
R41, R42, R43 and R44 are each independently as defined above;
R46 and R47 are each independently selected from the group consisting of H, alkyl and aryl, or taken together form a ring structure;
R48 and R49 are each independently selected from the group consisting of H, alkyl, aryl, alkoxy, alkyl interrupted by oxa, aryloxyalkyl, alkoxyaryl, and halogen-substituted versions thereof;
R50, R51 and R52 are each independently selected from the group consisting of H, alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenyloxy, allkenylthio, aryloxy, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylakyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, and hydroxyarylalkyl; and
m is an integer of from 1 to 3
and wherein, optionally, any two of R1, R2, R3 and R4 are combined to form a ring structure;
and dimers of Formula I, said dimers being formed by the covalent attachment of two complexing agents of Formula I through a linking group having from 1 to 6 carbon atoms; and physiological salts thereof;
with the proviso that the molecular weight of said complexing agent does not exceed 2000.
4. A method of inhibiting metalloenzymes containing first transition series metal cations in a subject, comprising administering or applying to said subject a complexing agent having the formula:
222
wherein,
p and q are independently either 2 or 3;
r is an integer of from 1 to 4;
R2, R3, and R4 are each independently selected from the group consisting of H, alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenoxy, alkenylthio, aryloxy, arylthio, alkyl interrupted by oxa, alkenyl interrupted by oxa, alkyl interrupted by thia, alkenyl interrupted by thia, aryloxyalkyl, alkoxyaryl, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, hydroxyarylalkyl, and halogen-substituted versions thereof;
R1 is a member selected from the group consisting of R2, R3, R4, and radicals of the formula:
223
wherein,
R41, R42, and R43 are each independently selected from the group consisting of H, alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenoxy, alkenylthio, aryloxy, arylthio, alkyl interrupted by oxa, alkenyl interrupted by oxa, alkyl interrupted by thia, alkenyl interrupted by thia, aryloxyalkyl, alkoxyaryl, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, hydroxyarylalkyl, and halogen-substituted versions thereof;
R44 is a member selected from the group consisting of H, hydroxy, amino, alkyl interrupted by oxa, alkoxy, aryl, aryloxyalkyl, alkoxyaryl, alkoxyaryl, and halogen-substituted versions thereof;
n is zero or 1; and
X is a member selected from the group consisting of alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenoxy, alkenylthio, aryloxy, arylthio, alkyl interrupted by oxa, alkenyl interrupted by oxa, alkyl interrupted by thia, alkenyl interrupted by thia, aryloxyalkyl, alkoxyaryl, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, hydroxyarylalkyl, halogen-substituted versions thereof, and radicals selected form the group consisting of:
224
wherein,
R41, R42, R43 and R44 are each independently as defined above;
R46 and R47 are each independently selected from the group consisting of H, alkyl and aryl, or taken together form a ring structure;
R48 and R49 are each independently selected from the group consisting of H, alkyl, aryl, alkoxy, alkyl interrupted by oxa, aryloxyalkyl, alkoxyaryl, and halogen-substituted versions thereof;
R50, R51 and R52 are each independently selected from the group consisting of H, alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenyloxy, allkenylthio, aryloxy, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylakyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, and hydroxyarylalkyl; and
m is an integer of from 1 to 3
and wherein, optionally, any two of R1, R2, R3 and R4 are combined to form a ring structure;
and dimers of Formula I, said dimers being formed by the covalent attachment of two complexing agents of Formula I through a linking group having from 1 to 6 carbon atoms; and physiological salts thereof;
with the proviso that the molecular weight of said complexing agent does not exceed 2000.
5. A method of inhibiting reperfusion injury in a subject, comprising administering to said subject a complexing agent having the formula:
225
wherein,
p and q are independently integers of from 2 to 3;
r is an integer of from 1 to 4;
R2, R3, and R4 are each independently selected from the group consisting of H, alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenoxy, alkenylthio, aryloxy, arylthio, alkyl interrupted by oxa, alkenyl interrupted by oxa, alkyl interrupted by thia, alkenyl interrupted by thia, aryloxyalkyl, alkoxyaryl, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, hydroxyarylalkyl, and halogen-substituted versions thereof;
R1 is a member selected from the group consisting of R2, R3, R4, and radicals of the formula:
226
wherein,
R41, R42, and R43 are each independently selected from the group consisting of H, alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenoxy, alkenylthio, aryloxy, arylthio, alkyl interrupted by oxa, alkenyl interrupted by oxa, alkyl interrupted by thia, alkenyl interrupted by thia, aryloxyalkyl, alkoxyaryl, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, hydroxyarylalkyl, and halogen-substituted versions thereof;
R44 is a member selected from the group consisting of H, hydroxy, amino, alkyl interrupted by oxa, alkoxy, aryl, aryloxyalkyl, alkoxyaryl, alkoxyaryl, and halogen-substituted versions thereof;
n is zero or 1; and
X is a member selected from the group consisting of alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenoxy, alkenylthio, aryloxy, arylthio, alkyl interrupted by oxa, alkenyl interrupted by oxa, alkyl interrupted by thia, alkenyl interrupted by thia, aryloxyalkyl, alkoxyaryl, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, hydroxyarylalkyl, halogen-substituted versions thereof, and radicals selected form the group consisting of:
227
wherein,
R41, R42, and R44 are each independently as defined above;
R46 and R47 are each independently selected from the group consisting of H, alkyl and aryl, or taken together form a ring structure;
R48 and R49 are each independently selected from the group consisting of H, alkyl, aryl, alkoxy, alkyl interrupted by oxa, aryloxyalkyl, alkoxyaryl, and halogen-substituted versions thereof;
R50, R51 and R52 are each independently selected from the group consisting of H, alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenyloxy, allkenylthio, aryloxy, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylakyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, and hydroxyarylalkyl; and
m is an integer of from 1 to 3
and wherein, optionally, any two of R1, R2, R3 and R4 are combined to form a ring structure;
and dimers of Formula I, said dimers being formed by the covalent attachment of two complexing agents of Formula I through a linking group having from 1 to 6 carbon atoms; and physiological salts thereof;
with the proviso that the molecular weight of said complexing agent does not exceed 2000.
6. A method for inhibiting body odors in a subject comprising administering to said subject a cosmeticpersonal care product into which is incorporated a complexing agent having the formula
228
wherein,
t, u and v are each independently 2 or 3;
w is an integer of from 1 to 4;
R11 and R13 are each independently selected from the group consisting of H, alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenoxy, alkenylthio, aryloxy, arylthio, alkyl interrupted by oxa, alkenyl interrupted by oxa, alkyl interrupted by thia, alkenyl interrupted by thia, aryloxyalkyl, alkoxyaryl, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, hydroxyarylalkyl, and halogen-substituted versions thereof;
R11 is a member selected from the group consisting of R11, R12 and radicals of the formula:
229
wherein,
R41, R42, and R43 are each independently selected from the group consisting of H, alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenoxy, alkenylthio, aryloxy, arylthio, alkyl interrupted by oxa, alkenyl interrupted by oxa, alkyl interrupted by thia, alkenyl interrupted by thia, aryloxyalkyl, alkoxyaryl, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, hydroxyarylalkyl, and halogen-substituted versions thereof;
R44 is a member selected from the group consisting of H, hydroxy, amino, alkyl interrupted by oxa, alkoxy, aryl, aryloxyalkyl, alkoxyaryl, alkoxyaryl, and halogen-substituted versions thereof;
n is zero or 1; and
X is a member selected from the group consisting of alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenoxy, alkenylthio, aryloxy, arylthio, alkyl interrupted by oxa, alkenyl interrupted by oxa, alkyl interrupted by thia, alkenyl interrupted by thia, aryloxyalkyl, alkoxyaryl, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, hydroxyarylalkyl, halogen-substituted versions thereof, and radicals selected form the group consisting of:
230
wherein,
R41, R42, R43 and R44 are each independently as defined above;
R46 and R47 are each independently selected from the group consisting of H, alkyl and aryl, or taken together form a ring structure;
R48 and R49 are each independently selected from the group consisting of H, alkyl, aryl, alkoxy, alkyl interrupted by oxa, aryloxyalkyl, alkoxyaryl, and halogen-substituted versions thereof;
R50, R51 and R52 are each independently selected from the group consisting of H, alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenyloxy, allkenylthio, aryloxy, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylakyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, and hydroxyarylalkyl; and
m is an integer of from 1 to 3
and wherein, optionally, any two of R11, R12 and R13 are combined to form a ring structure;
and dimers of Formula II, said dimers being formed by the covalent attachment of two complexing agents of Formula II through a linking group having from 1 to 6 carbon atoms; and physiological salts thereof;
with the proviso that the molecular weight of said complexing agent does not exceed 2000.
7. A method for inhibiting tooth decay, gum disease and periodontal disease in a subject comprising administering to said subject an oral care product into which is incorporated a complexing agent having the formula
231
wherein,
t, u and v are each independently 2 or 3;
w is an integer of from 1 to 4;
R11 and R13 are each independently selected from the group consisting of H, alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenoxy, alkenylthio, aryloxy, arylthio, alkyl interrupted by oxa, alkenyl interrupted by oxa, alkyl interrupted by thia, alkenyl interrupted by thia, aryloxyalkyl, alkoxyaryl, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, hydroxyarylalkyl, and halogen-substituted versions thereof;
R11 is a member selected from the group consisting of R11, R12 and radicals of the formula:
232
wherein,
R41, R42, and R43 are each independently selected from the group consisting of H, alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenoxy, alkenylthio, aryloxy, arylthio, alkyl interrupted by oxa, alkenyl interrupted by oxa, alkyl interrupted by thia, alkenyl interrupted by thia, aryloxyalkyl, alkoxyaryl, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, hydroxyarylalkyl, and halogen-substituted versions thereof;
R44 is a member selected from the group consisting of H, hydroxy, amino, alkyl interrupted by oxa, alkoxy, aryl, aryloxyalkyl, alkoxyaryl, alkoxyaryl, and halogen-substituted versions thereof;
n is zero or 1; and
X is a member selected from the group consisting of alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenoxy, alkenylthio, aryloxy, arylthio, alkyl interrupted by oxa, alkenyl interrupted by oxa, alkyl interrupted by thia, alkenyl interrupted by thia, aryloxyalkyl, alkoxyaryl, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, hydroxyarylalkyl, halogen-substituted versions thereof, and radicals selected form the group consisting of:
233
wherein,
R41, R42, R43 and R44 are each independently as defined above;
R46 and R47 are each independently selected from the group consisting of H, alkyl and aryl, or taken together form a ring structure;
R48 and R49 are each independently selected from the group consisting of H, alkyl, aryl, alkoxy, alkyl interrupted by oxa, aryloxyalkyl, alkoxyaryl, and halogen-substituted versions thereof;
R50, R51 and R52 are each independently selected from the group consisting of H, alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenyloxy, alkenylthio, aryloxy, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylakyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, and hydroxyarylalkyl; and
m is an integer of from 1 to 3
and wherein, optionally, any two of R11, R12, and R13 are combined to form a ring structure;
and dimers of Formula II, said dimers being formed by the covalent attachment of two complexing agents of Formula II through a linking group having from 1 to 6 carbon atoms; and physiological salts thereof;
with the proviso that the molecular weight of said complexing agent does not exceed 2000.
8. A method for inhibiting oxidative damage to skin and skin appendages in a subject comprising administering to said subject a skin and skin appendage product into which is incorporated a complexing agent having the formula
234
wherein,
t, u and v are each independently 2 or 3;
w is an integer of from 1 to 4;
R11 and R13 are each independently selected from the group consisting of H, alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenoxy, alkenylthio, aryloxy, arylthio, alkyl interrupted by oxa, alkenyl interrupted by oxa, alkyl interrupted by thia, alkenyl interrupted by thia, aryloxyalkyl, alkoxyaryl, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, hydroxyarylalkyl, and halogen-substituted versions thereof;
R11 is a member selected from the group consisting of R11, R12 and radicals of the formula:
235
wherein,
R41, R42, and R43 are each independently selected from the group consisting of H, alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenoxy, alkenylthio, aryloxy, arylthio, alkyl interrupted by oxa, alkenyl interrupted by oxa, alkyl interrupted by thia, alkenyl interrupted by thia, aryloxyalkyl, alkoxyaryl, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, hydroxyarylalkyl, and halogen-substituted versions thereof;
R44 is a member selected from the group consisting of H, hydroxy, amino, alkyl interrupted by oxa, alkoxy, aryl, aryloxyalkyl, alkoxyaryl, alkoxyaryl, and halogen-substituted versions thereof;
n is zero or 1; and
X is a member selected from the group consisting of alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenoxy, alkenylthio, aryloxy, arylthio, alkyl interrupted by oxa, alkenyl interrupted by oxa, alkyl interrupted by thia, alkenyl interrupted by thia, aryloxyalkyl, alkoxyaryl, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, hydroxyarylalkyl, halogen-substituted versions thereof, and radicals selected form the group consisting of:
236
wherein,
R41, R42, R43 and R44 are each independently as defined above;
R46 and R47 are each independently selected from the group consisting of H, alkyl and aryl, or taken together form a ring structure;
R48 and R49 are each independently selected from the group consisting of H, alkyl, aryl, alkoxy, alkyl interrupted by oxa, aryloxyalkyl, alkoxyaryl, and halogen-substituted versions thereof;
R50, R51 and R52 are each independently selected from the group consisting of H, alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenyloxy, allkenylthio, aryloxy, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylakyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, and hydroxyarylalkyl; and
m is an integer of from 1 to 3
and wherein, optionally, any two of R11, R12, and R13 are combined to form a ring structure;
and dimers of Formula II, said dimers being formed by the covalent attachment of two complexing agents of Formula II through a linking group having from 1 to 6 carbon atoms; and physiological salts thereof;
with the proviso that the molecular weight of said complexing agent does not exceed 2000.
9. A method for inhibiting metalloenzymes containing first transition series elements in a subject comprising administering to said subject a complexing agent having the formula
237
wherein,
t, u and v are each independently 2 or 3;
w is an integer of from 1 to 4;
R11 and R13 are each independently selected from the group consisting of H, alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenoxy, alkenylthio, aryloxy, arylthio, alkyl interrupted by oxa, alkenyl interrupted by oxa, alkyl interrupted by thia, alkenyl interrupted by thia, aryloxyalkyl, alkoxyaryl, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, hydroxyarylalkyl, and halogen-substituted versions thereof;
R11 is a member selected from the group consisting of R11, R12 and radicals of the formula:
238
wherein,
R41, R42, and R43 are each independently selected from the group consisting of H, alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenoxy, alkenylthio, aryloxy, arylthio, alkyl interrupted by oxa, alkenyl interrupted by oxa, alkyl interrupted by thia, alkenyl interrupted by thia, aryloxyalkyl, alkoxyaryl, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, hydroxyarylalkyl, and halogen-substituted versions thereof;
R44 is a member selected from the group consisting of H, hydroxy, amino, alkyl interrupted by oxa, alkoxy, aryl, aryloxyalkyl, alkoxyaryl, alkoxyaryl, and halogen-substituted versions thereof;
n is zero or 1; and
X is a member selected from the group consisting of alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenoxy, alkenylthio, aryloxy, arylthio, alkyl interrupted by oxa, alkenyl interrupted by oxa, alkyl interrupted by thia, alkenyl interrupted by thia, aryloxyalkyl, alkoxyaryl, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, hydroxyarylalkyl, halogen-substituted versions thereof, and radicals selected form the group consisting of:
239
wherein,
R41, R42, R43 and R44 are each independently as defined above;
R46 and R47 are each independently selected from the group consisting of H, alkyl and aryl, or taken together form a ring structure;
R48 and R49 are each independently selected from the group consisting of H, alkyl, aryl, alkoxy, alkyl interrupted by oxa, aryloxyalkyl, alkoxyaryl, and halogen-substituted versions thereof;
R50, R51 and R52 are each independently selected from the group consisting of H, alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenyloxy, allkenylthio, aryloxy, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylakyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, and hydroxyarylalkyl; and
m is an integer of from 1 to 3
and wherein, optionally, any two of R11, R12, and R13 are combined to form a ring structure;
and dimers of Formula II, said dimers being formed by the covalent attachment of two complexing agents of Formula II through a linking group having from 1 to 6 carbon atoms; and physiological salts thereof;
with the proviso that the molecular weight of said complexing agent does not exceed 2000.
10. A method for inhibiting reperfusion injury in a subject comprising administering to said subject a complexing agent having the formula
240
wherein
t, u and v are each independently 2 or 3;
w is an integer of from 1 to 4;
R11 and R13 are each independently selected from the group consisting of H, alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenoxy, alkenylthio, aryloxy, arylthio, alkyl interrupted by oxa, alkenyl interrupted by oxa, alkyl interrupted by thia, alkenyl interrupted by thia, aryloxyalkyl, alkoxyaryl, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, hydroxyarylalkyl, and halogen-substituted versions thereof;
R11 is a member selected from the group consisting of R11, R12 and radicals of the formula:
241
wherein,
R41, R42, and R43 are each independently selected from the group consisting of H, alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenoxy, alkenylthio, aryloxy, arylthio, alkyl interrupted by oxa, alkenyl interrupted by oxa, alkyl interrupted by thia, alkenyl interrupted by thia, aryloxyalkyl, alkoxyaryl, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, hydroxyarylalkyl, and halogen-substituted versions thereof;
R44 is a member selected from the group consisting of H, hydroxy, amino, alkyl interrupted by oxa, alkoxy, aryl, aryloxyalkyl, alkoxyaryl, alkoxyaryl, and halogen-substituted versions thereof;
n is zero or 1; and
X is a member selected from the group consisting of alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenoxy, alkenylthio, aryloxy, arylthio, alkyl interrupted by oxa, alkenyl interrupted by oxa, alkyl interrupted by thia, alkenyl interrupted by thia, aryloxyalkyl, alkoxyaryl, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, hydroxyarylalkyl, halogen-substituted versions thereof, and radicals selected form the group consisting of:
242
wherein,
R41, R42, R43 and R44 are each independently as defined above;
R46 and R47 are each independently selected from the group consisting of H, alkyl and aryl, or taken together form a ring structure;
R48 and R49 are each independently selected from the group consisting of H, alkyl, aryl, alkoxy, alkyl interrupted by oxa, aryloxyalkyl, alkoxyaryl, and halogen-substituted versions thereof;
R50, R51 and R52 are each independently selected from the group consisting of H, alkyl, alkenyl, aryl, arylalkyl, alkoxy, alkylthio, alkenyloxy, allkenylthio, aryloxy, aminoalkyl, aminoalkenyl, aminoaryl, aminoarylakyl, hydroxyalkyl, hydroxyalkenyl, hydroxyaryl, and hydroxyarylalkyl; and
m is an integer of from 1 to 3
and wherein, optionally, any two of R11, R12, and R13 are combined to form a ring structure;
and dimers of formula II, said dimers being formed by the covalent attachment of two complexing agents of Formula II through a linking group having from 1 to 6 carbon atoms; and physiological salts thereof;
with the proviso that the molecular weight of said complexing agent does not exceed 2000.
11. A method in accordance with claim 6 in which said complexing agent is N,N,N-tri(dihydroxyphosphoryl methyl)-1,4,7-triazacyclononane.
12. A method in accordance with claim 7 in which said complexing agent is N,N,N-tri(dihydroxyphosphoryl methyl)-1,4,7-triazacyclononane.
13. A method in accordance with claim 8 in which said complexing agent is N,N,N-tri(dihydroxyphosphoryl methyl)-1,4,7-triazacyclononane.
14. A method in accordance with claim 9 in which said complexing agent is N,N,N-tri(dihydroxyphosphoryl methyl)-1,4,7-triazacyclononane.
15. A method in accordance with claim 10 in which said complexing agent is N,N,N-tri(dihydroxyphosphoryl methyl)-1,4,7-triazacyclononane.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A system for managing care of a person receiving emergency cardiac assistance, the system comprising:
one or more capacitors for delivering a defibrillating shock to a patient;
one or more electronic ports for receiving signals from sensors for obtaining indications of an electrocardiogram (ECG) for the patient; and
a patient treatment module executable on one or more computer processors to provide a determination of a likelihood of success from delivering a future defibrillating shock to the person with the one or more capacitors, using (a) information about a prior defibrillating shock, and (b) a value that is a function of current ECG signals from the patient.
2. The system of claim 1, further comprising an output mechanism arranged to indicate, to a user of the system, an indication regarding the likelihood of success form delivering a defibrillating shock to the person with the one or more capacitors.
3. The system of claim 2, wherein the output mechanism comprises a visual display, and the system is programmed to display to the user one of multiple possible indications that each indicate a degree of likelihood of success.
4. The system of claim 1, wherein the output mechanism comprises an interlock that prevents a user from delivering a shock unless the determined likelihood of success exceeds a determined value.
5. The system of claim 1, wherein the patient treatment module comprises an ECG analyzer for generating an amplitude spectrum area (AMSA) value, and wherein the patient treatment module uses the information about the level of success from the prior defibrillating shock to adjust the AMSA value.
6. The system of claim 1, wherein the patient treatment module comprises an ECG analyzer for generating an indication of heart rate for the patent.
7. The system of claim 1, wherein the patient treatment module comprises an ECG analyzer for generating an indication heart rate variability for the patent.
8. The system of claim 1, wherein the patient treatment module comprises an ECG analyzer for generating an indication of ECG amplitude for the patent.
9. The system of claim 8, wherein the indication of ECG amplitude comprises an RMS measurement, measured peak-to-peak, peak-to-trough, or an average of peak-to-peak or peak-to-trough over a specified interval
10. The system of claim 1, wherein the patient treatment module comprises an ECG analyzer for generating an indication of a first derivative of ECG amplitude for the patent.
11. The system of claim 1, wherein the patient treatment module comprises an ECG analyzer for generating an indication of a second derivative of ECG amplitude for the patent.
12. The system of claim 1, where the patient treatment module is programmed to determine whether a prior defibrillation shock was at least partially successful, and based at least in part on the determination of whether the prior defibrillation was at least partially successful, modifying a calculation of the likelihood of success from delivering the future defibrillating shock.
13. The system of claim 1, wherein determining a likelihood of success from delivering a future defibrillating shock to the person depends on a determination of whether one or more prior shocks delivered to the person were successful in defibrillating the person.
14. The system of claim 1, wherein determining a likelihood of success from delivering a future defibrillating shock comprises performing a mathematical transform on the ECG data.
15. The system of claim 14, wherein the mathematical transform is selected form a group consisting of Fourier, discrete Fourier, Hilbert, discrete Hilbert, wavelet, and discrete wavelet methods.
16. The system of claim 1, wherein determining a likelihood of success from delivering a future defibrillating shock comprises performing a calculation by an operation selected form a group consisting of logistic regression, table look-up, neural network, and fuzzy logic.
17. The system of claim 1, wherein the patient treatment module is programmed to determine the likelihood of success from delivering a future defibrillating shock using at least one patient-dependent physical parameter separate from a patient ECG reading.
18. The system of claim 1, wherein the patient treatment module is programmed to determine the likelihood of success from delivering a future defibrillating shock using at a measure of trans-thoracic impedance of the person.
19. A method for managing care of a person receiving emergency cardiac assistance, the method comprising:
monitoring, with an external defibrillator, electrocardiogram (ECG) data from a person receiving emergency cardiac assistance;
determining whether a prior defibrillation shock occurred;
determining a likelihood of future defibrillation shock success using at least the ECG data;
based at least in part on the determination of whether the prior defibrillation occurred, modifying the calculation of the chance of defibrillation shock success; and
affecting control of the external defibrillator based on the identification of whether a present defibrillation shock will likely be effective.
20. The method of claim 19, wherein determining a likelihood of future defibrillation shock success comprises determining a value that is a function of electrocardiogram amplitude at particular different frequencies or frequency ranges.
21. The method of claim 20, wherein determining a likelihood of future defibrillation shock success comprises determining an amplitude spectrum area (AMSA) value for the ECG data.
22. The method of claim 21, wherein determining a likelihood of future defibrillation shock success further comprises adjusting the determined AMSA value using information about the prior defibrillation shock.
23. The method of claim 22, further comprising determining whether the adjusted AMSA value exceeds a predetermined threshold value.
24. The method of claim 23, further comprising providing to the rescuer a visual, audible, or tactile alert that a shockable situation exists for the person, if the adjusted AMSA value is determined to exceed the predetermined threshold value.
25. The method of claim 19, further comprising determining whether a prior defibrillation shock was at least partially successful, and based at least in part on the determination of whether the prior defibrillation was at least partially successful, modifying a calculation of the likelihood of success from delivering the future defibrillating shock.
26. The method of claim 19, wherein determining a likelihood of success from delivering a future defibrillating shock comprises performing a mathematical transform on the ECG data.
27. The method of claim 26, wherein the mathematical transform is selected form a group consisting of Fourier, discrete Fourier, Hilbert, wavelet, and discrete wavelet methods.
28. The method of claim 27, wherein determining a likelihood of success from delivering a future defibrillating shock comprises performing a calculation by an operation selected form a group consisting of logistic regression, table look-up, neural network, and fuzzy logic.
29. The method of claim 19, where the likelihood of success from delivering a future defibrillating shock is determined using at least one patient-dependent physical parameter separate from a patient ECG reading.
30. The method of claim 19, wherein the additional physiologic parameter is trans-thoracic impedance of the person receiving emergency cardiac care.
31. The method of claim 19, wherein the indication of trans-thoracic impedance is determined from signals sensed by a plurality of electrocardiogram leads that also provide the EGO data.
32. The method of claim 19, further comprising cyclically repeating the actions of monitoring, determining, identifying and providing the indication.
33. The method of claim 19, further comprising identifying compression depth of chest compressions performed on the person, using a device on the person’s sternum and in communication with the external defibrillator, and providing feedback to a rescuer performing the chest compressions regarding rate of compression, depth of compression, or both.
34. The method of claim 19, wherein affecting control of the defibrillator comprises preventing a user from delivering a shock unless the determination of whether a shock will be effective exceeds a determined likelihood level.
35. The method of claim 19, wherein affecting control of the defibrillator comprises electronically displaying, to a user, an indicator of the determined indication of whether a shock will be effective.
36. The method of claim 19, wherein displaying an indicator comprises displaying a value, of multiple possible values in a range, that indicates a likelihood of success.
37. The method of claim 19, wherein the calculation of the likelihood of current shock success is determined or modified using a determination of a value of trans-thoracic impedance of the person.