Oral formulations of mitochondrially-targeted antioxidants and their preparation and use
AssigneeMitotech SA
InventorsMaxim V. Skulachev, Vladimir P. Skulachev, Audrey A. Zamyatnin, Vadim N. Tashlitsky, Roman A. Zinovkin, Maxim V. Egorov, Lawrence T. Friedhoff, Olga Y. Pletushkina, Alexander A. Andreev-Andrievsky, Tatiana V. Zinevich
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Abstract
Provided are stable liquid and solid formulations of oxidized and reduced mitochondria-targeted antioxidants, and methods of their preparation and use.
Claims9
A method of treating dermal wounds, comprising orally administering to a patient in need thereof a therapeutically effective amount of a formulation comprising a compound of Formula I, in liquid or solid form:
- wherein:
- A is an antioxidant having the structure of Formula II:
- and/or reduced form thereof, wherein:
- m comprises an integer from 1 to 3;
- Y is methyl;
- L is a linker group, comprising a straight or branched hydrocarbon chain optionally substituted by one or more double or triple bond, or ether bond, or ester bond, or C—S, or S—S, or peptide bond;
- and which is optionally substituted by one or more substituents selected from alkyl, alkoxy, halogen, keto group, amino group;
- n is an integer from 1 to 20;
- and
- B is a targeting group, and is:
- a Skulachev ion Sk+Z−, wherein:
- Sk is a lipophilic cation or a lipophilic metalloporphyrin;
- and
- Z is a pharmaceutically acceptable anion,
- the compound being stabilized in about 10% to about 100% of a liquid solvent selected from the group consisting of propylene glycol and glycerol.
A method of treating an inflammatory disorder, comprising orally administering to a patient in need thereof a therapeutically effective amount of formulation comprising a stabilized compound of Formula I in liquid or solid form:
- wherein:
- A is an antioxidant having the structure of Formula II:
- and/or reduced form thereof, wherein:
- m comprises an integer from 1 to 3;
- Y is methyl;
- L is a linker group, comprising a straight or branched hydrocarbon chain optionally substituted by one or more double or triple bond, or ether bond, or ester bond, or C—S, or S—S, or peptide bond;
- and which is optionally substituted by one or more substituents selected from alkyl, alkoxy, halogen, keto group, amino group;
- n is an integer from 1 to 20;
- and
- B is a targeting group, and is:
- a Skulachev ion Sk+Z−, wherein:
- Sk is a lipophilic cation or a lipophilic metalloporphyrin;
- and
- Z is a pharmaceutically acceptable anion,
- the compound being stabilized in about 10% to about 100% of a liquid solvent selected from the group consisting of propylene glycol and glycerol.
A pharmaceutical formulation comprising a compound of Formula I in oxidized and/or reduced form in a light-protected vial, the compound of Formula I being:
- wherein:
- A is an antioxidant having the structure of Formula II:
- and/or reduced form thereof, wherein:
- m comprises an integer from 1 to 3;
- Y is methyl;
- L is a linker group comprising a straight or branched hydrocarbon chain optionally substituted by one or more double or triple bond, or ether bond, or ester bond, or C—S, or S—S, or peptide bond;
- and which is optionally substituted by one or more substituents selected from alkyl, alkoxy, halogen, keto group, amino group;
- n is an integer from 1 to 20;
- and
- B is a targeting group, and is:
- a Skulachev ion Sk+Z−, wherein:
- Sk is a lipophilic cation or a lipophilic metalloporphyrin;
- and
- Z is a pharmaceutically acceptable anion,
- the compound being stabilized in about 10% to about 100% of a liquid solvent selected from the group consisting of propylene glycol and glycerol.
A pharmaceutical formulation comprising a compound of Formula I in oxidized or reduced form:
- wherein:
- A is an antioxidant having the structure of Formula II:
- and/or reduced form thereof, wherein:
- m comprises an integer from 1 to 3;
- Y is methyl;
- L is a linker group comprising a straight or branched hydrocarbon chain optionally substituted by one or more double or triple bond, or ether bond, or ester bond, or C—S, or S—S, or peptide bond;
- and which is optionally substituted by one or more substituents selected from alkyl, alkoxy, halogen, keto group, amino group;
- n is an integer from 1 to 20;
- and
- B is a targeting group, and is:
- a Skulachev ion Sk+Z−, wherein:
- Sk is a lipophilic cation or a lipophilic metalloporphyrin;
- and
- Z is a pharmaceutically acceptable anion,
- the compound being stabilized in about 10% to about 100% of a liquid solvent selected from the group consisting of propylene glycol and glycerol.
Dependencies are inferred from the claim text.