Methods employing and compositions containing defined oxidized phospholipids for prevention and treatment of atherosclerosis
AssigneeVascular Biogenics Ltd.
InventorsDror Harats, Jacob George, Gideon Halperin
Life of this patent
Estimating the term…
Abstract
Novel synthetic forms of etherified oxidized phospholipids and methods of utilizing same for preventing and treating atherosclerosis and other related disorders, as well as inflammatory disorders, immune mediated diseases, autoimmune diseases and proliferative disorders, are provided. In addition, methods of synthesizing etherified and esterified oxidized phospholipids and of using same for preventing and treating atherosclerosis and other related disorders are also provided.
Claims19
A method of prevention and/or treatment of atherosclerosis, cardiovascular disease, cerebrovascular disease, peripheral vascular disease, stenosis, restenosis and/or in-stent-stenosis in a subject in need thereof, the method comprising administering a therapeutically effective amount of a compound, said compound selected from the group having a formula:
- 14
- or pharmaceutically acceptable salts thereof, wherein:
- (i) A1 and A2 are each independently selected from the group consisting of CH2 and C═O, at least one of A1 and A2 being CH2;
- (ii) R1 and R2 are each independently selected from the group consisting of an alkyl chain having 1-27 carbon atoms and
- 15
- wherein X is an alkyl chain having 1-24 carbon atoms, Y is selected from the group consisting of:
- 16
- —OH, —H, alkyl, alkoxy halogen, acetoxy and aromatic functional groups;and
- Z is selected from the group consisting of:
- 17
- and —OH, whereas R4 is an alkyl,
- at least one of R1 and R2 being said
- 18
- and
- (iii) R3 is selected from the group consisting of H, acyl, alkyl, phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl serine, phosphatidyl cardiolipin and phosphatidyl inisitol.
A method of prevention and/or treatment of an inflammatory disorder, an immune mediated disease, an autoimmune disease and a proliferative disorder selected from the group consisting of aging, rheumatoid arthritis, juvenile rheumatoid arthritis, inflammatory bowl disease and cancer in a subject in need thereof, the method comprising administering a therapeutically effective amount of a compound, said compound selected from the group having a formula:
- 22
- or pharmaceutically acceptable salts thereof, wherein:
- (i) A1 and A2 are each independently selected from the group consisting of CH2 and C═O, at least one of A1 and A2 being CH2;
- (ii) R1 and R2 are each independently selected from the group consisting of an alkyl chain having 1-27 carbon atoms and
- 23
- wherein X is an alkyl chain having 1-24 carbon atoms, Y is selected from the group consisting of:
- 24
- —OH, —H, alkyl, alkoxy halogen, acetoxy and aromatic functional groups;and
- Z is selected from the group consisting of:
- 25
- whereas R4 is an alkyl,
- at least one of R1 and R2 being said
- 26
- and
- (iii) R3 is selected from the group consisting of H, acyl, alkyl, phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl serine, phosphatidyl cardiolipin and phosphatidyl inisitol.
A method of synthesizing an oxidized phospholipid comprising:
- (a) providing a phospholipid backbone including two fatty acid side chains, wherein at least one of said fatty acid side chains is a mono-unsaturated fatty acid having 2-15 carbon atoms;
- and
- (b) oxidizing the unsaturated bond of said mono-unsaturated fatty acid to thereby generate the oxidized phospholipid.
Dependencies are inferred from the claim text.