Liposomal formulations comprising AT1 receptor blockers and uses thereof
AssigneeYissum Research Development Company of the Hebrew University of Jerusalem
InventorsYechezkel Barenholz, Ahuva Cern, Amiram Goldblum
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Abstract
The present disclosure provides liposomal formulations comprising a lipid membrane comprising at least one liposome forming phospholipid and a sterol; and an intraliposomal aqueous compartment encapsulating at least one ATI receptor blocker (ARB) and a pH-dependent ionizable anion; with the liposomes having an effect upon administration to a subject in need of said effect, without causing a reduction in mean blood pressure of said subject of more than 50% as compared to the administration of the same amount of ARB in free form. The liposomes can be for systemic administration, e.g. by injection or for pulmonary administration, e.g. by inhalation.
Claims18
Liposomes, comprising:
- a lipid membrane comprising at least one liposome forming phospholipid and a sterol;
- and
- an intraliposomal aqueous compartment encapsulating at least one AT1 receptor blocker, ARB, and a pH-dependent ionizable anion;
- wherein:
- the at least one ARB is selected from the group consisting of (2S)-3-methyl-2-[pentanoyl-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]amino]butanoic acid (Valsartan) of Formula I:
- and 2-ethoxy-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]benzimidazole-4-carboxylic acid (Candesartan) of Formula II:
- the at least one liposome forming phospholipid and the sterol are present at a weight ratio of between 3:1 and 2:1;
- the liposomes have a molar ratio between the at least one ARB and the at least one phospholipid within the range of 0.02 to 1.0;
- and
- the at least one ARB is selected to provide, upon systemic administration of the liposomes, to a subject in need thereof, an effect, without causing a reduction in mean blood pressure of said subject of more than 50% as compared to systemic administration of the same amount of ARB in free form.
Liposomes, comprising:
- a lipid membrane comprising at least one liposome forming phospholipid and a sterol;
- and
- an intraliposomal aqueous compartment encapsulating at least one AT1 receptor blocker, ARB;
- said liposomes have an average size of between 50 nm and 600 nm,
- wherein said liposomes have an effect on a subject's respiratory tract, upon administration by inhalation, without causing a reduction in mean blood pressure in said subject of more than 50% as compared to inhalation of the same amount of ARB in free form.
A method of treating a condition along a subject's respiratory tract, the method comprising:
- administering to said subject, liposomes comprising:
- a lipid membrane comprising at least one liposome forming phospholipid and a sterol;
- and
- an intraliposomal aqueous compartment encapsulating at least one AT1 receptor blocker, ARB;
- wherein the at least one ARB is selected from the group consisting of (2S)-3-methyl-2-[pentanoyl-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]amino]butanoic acid (Valsartan) of Formula I:
- and 2-ethoxy-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]benzimidazole-4-carboxylic acid (Candesartan) of Formula II:
- wherein said liposomes have an average size of between 50 nm and 600 nm;
- and
- wherein said method comprises selecting the ARB to provide, upon administration by inhalation of the liposomes, an effect on a subject's respiratory tract, without causing a reduction in mean blood pressure in said subject of more than 50% as compared to inhalation of the same amount of ARB in free form.
Dependencies are inferred from the claim text.