Pharmaceutical formulations containing mitochondrially targeted antioxidants
AssigneeMitotech SA
InventorsMaxim V. Skulachev, Vladimir P. Skulachev, Egor Y. Plotnikov, Dmitry B. Zorov, Roman A. Zinovkin, Alexander N. Lukashev, Maxim V. Egorov, Maxim L. Lovat, Anton Petrov
Life of this patent
Estimating the term…
Abstract
The present disclosure provides methods of preventing activation of neutrophils with mitochondrially targeted anti-oxidants. Also disclosed are methods of preventing or treating different inflammatory diseases and inflammation-related conditions with MTAs.
Claims15
1-19. (canceled)
A method of treatment of an inflammatory disorder comprising preventing neutrophil activation by contacting neutrophils with one or more mitochondrially targeted antioxidant having the structure:
- wherein:
- A is an effector moiety having a following structure:
- and reduced forms thereof, wherein:
- m is an integer from 1 to 3;
- each Y is independently selected from the group consisting of:
- lower alkyl;
- lower alkoxy;
- or
- two adjacent Y groups, together with carbon atoms to which they are attached, form a following structure:
- and reduced forms thereof;
- wherein:
- R1 and R2 may be the same or different and are each independently lower alkyl or lower alkoxy;
- L is a linker group, comprising:
- a) a straight or branched hydrocarbon chain which can be optionally substituted by one or more substituents and optionally contains one or more double or triple bonds;
- or
- b) a natural isoprene chain;
- n is integer from 1 to 40, or from 2 to 15, or from 5 to 11;
- B is a targeting group comprising Sk+T−, wherein:
- Sk is a lipophilic cation;
- and
- Z is a pharmacologically-acceptable anion;
- and solvates, salts, isomers or prodrugs thereof.
A method of lowering blood vessels permeability in a mammal suffering from a glucose metabolism disorder comprising administering to the mammal a therapeutically effective amount of one or more mitochondrially targeted antioxidant having the structure:
- wherein:
- A is an effector moiety having a following structure:
- and reduced forms thereof, wherein:
- m is an integer from 1 to 3;
- each Y is independently selected from the group consisting of:
- lower alkyl;
- lower alkoxy;
- or
- two adjacent Y groups, together with carbon atoms to which they are attached, form a following structure:
- and reduced forms thereof;
- wherein:
- R1 and R2 may be the same or different and are each independently lower alkyl or lower alkoxy;
- L is a linker group, comprising:
- a) a straight or branched hydrocarbon chain which can be optionally substituted by one or more substituents and optionally contains one or more double or triple bonds;
- or
- b) a natural isoprene chain;
- n is integer from 1 to 40, or from 2 to 15, or from 5 to 11;
- B is a targeting group comprising Sk+T−, wherein:
- Sk is a lipophilic cation;
- and
- Z is a pharmacologically-acceptable anion;
- and solvates, salts, isomers or prodrugs thereof,
- thereby preventing the disassembly of endothelial cell-to-cell contact in that mammal.
A method of treatment of an inflammatory disorder comprising prevention of MMP-9 release from activated neutrophils by contacting neutrophils with one or more mitochondrially targeted antioxidant having the structure:
- wherein:
- A is an effector moiety having a following structure:
- and reduced forms thereof, wherein:
- m is an integer from 1 to 3;
- each Y is independently selected from the group consisting of:
- lower alkyl;
- lower alkoxy;
- or
- two adjacent Y groups, together with carbon atoms to which they are attached, form a following structure:
- and reduced forms thereof;
- wherein:
- R1 and R2 may be the same or different and are each independently lower alkyl or lower alkoxy;
- L is a linker group, comprising:
- a) a straight or branched hydrocarbon chain which can be optionally substituted by one or more substituents and optionally contains one or more double or triple bonds;
- or
- b) a natural isoprene chain;
- n is integer from 1 to 40, or from 2 to 15, or from 5 to 11;
- B is a targeting group comprising Sk+T−, wherein:
- Sk is a lipophilic cation;
- and
- Z is a pharmacologically-acceptable anion;
- and solvates, salts, isomers or prodrugs thereof.
Dependencies are inferred from the claim text.