LIPID EMULSIONS AND USES THEREOF
The present disclosure provides lipid emulsions comprising at least 20 percent (w/v) lipid with an average particle size of about 200 to about 300 nm, and use thereof to treat subjects in need of lipid emulsion therapy.
1 . A lipid emulsion composition comprising at least 20 percent (w/v) lipid, about 1 to about 5 percent (w/v) emulsifier, about 1 to about 5 percent (w/v) tonicity modifier, about 58 to about 88 percent (w/v) water, and optionally an inotrope, wherein the particles in the lipid emulsion have an average particle diameter of about 200 nm to less than 300 nm.
2 . The composition of claim 1 , wherein the composition comprises about 24 percent (w/v) lipid.
3 . (canceled)
4 . The composition of claim 1 , wherein the particles have an average particle diameter of about 250 nm to less than 300 nm.
5 - 6 . (canceled)
7 . The composition of claim 1 , wherein the particles in the lipid emulsion have an average particle diameter of about 200 nm to about 250 nm.
8 - 12 . (canceled)
13 . The composition of claim 1 , wherein at least 50% of the particles have a particle diameter less than 250 nm.
14 - 25 . (canceled)
26 . The composition of claim 1 , wherein at least 90% of the particles have a particle diameter less than 250 nm, and at least 50% of the particle have a diameter of about 240 nm or less.
27 - 47 . (canceled)
48 . The composition of claim 1 , wherein the average particle diameter of the composition changes by 25% or less following storage at 25° C. for 3 months.
49 - 51 . (canceled)
52 . The composition of claim 1 , wherein the particles have increased surface area and/or a decreased zeta potential.
53 . The composition of claim 1 , wherein the lipid is soybean oil, avocado oil, flaxseed oil, coconut oil, cottonseed oil, squalene oil, groundnut oil, olive oil, canola oil, corn oil, rapeseed oil, safflower oil, sunflower oil, an animal oil, fish oil, flavor oil, water insoluble vitamins, mineral oil, or any combination thereof.
54 . The composition of claim 1 , wherein the emulsifier is a synthetic lecithin, such as dihexanoyl-L-a.-lecithin, or a phospholipid such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidylglycerol, phosphatidic acid, lysophospholipids, egg or soybean phospholipid or combinations thereof and the emulsifier may be in any form, including salted or desalted, hydrogenated or partially hydrogenated, or natural, modified, semisynthetic or synthetic.
55 . The composition of claim 1 , wherein the tonicity modifier is glycerin, sorbitol, a polyoxyethylated hydrocarbon, a C6-C20 saturated aliphatic acid, or a C6-C20 unsaturated aliphatic acid.
56 . The composition of claim 1 , wherein the lipid is soybean oil, the emulsifier is egg yolk phospholipids, and the tonicity modifier is glycerin.
57 . (canceled)
58 . A lipid emulsion composition comprising at least 20 percent (w/v) lipid, about 1 to about 5 percent (w/v) emulsifier, about 1 to about 5 percent (w/v) tonicity modifier, about 58 to about 88 percent (w/v) water, and optionally an inotrope, wherein the particles in the lipid emulsion have an average particle diameter of about 250 nm to less than about 315 nm.
59 . The composition of claim 58 , wherein
the composition comprises about 24 percent (w/v) lipid.
60 . (canceled)
61 . The composition of any of the above claims, wherein the particle size standard deviation is 150 nm or less.
62 - 64 . (canceled)
65 . A method of treating systemic drug toxicity, severe hypotension, or an ischemic/reperfusion injury in a subject in need thereof, the method comprising intravenously administering to the subject a lipid emulsion composition of any one of the preceding claims.
66 - 67 . (canceled)
68 . A method of improving cardiac function, improving organ perfusion, improving blood pressure, or reducing the therapeutic vasopressor dose in a patient in shock, wherein the patient has optionally been administered at least one high dose of a vasopressor, the method comprising intravenously administering a lipid emulsion.
69 - 71 . (canceled)
72 . A method of improving cardiac function, blood pressure, organ perfusion, or a combination thereof, in a patient diagnosed with end-stage heart failure, the method comprising intravenously administering a lipid emulsion.
73 - 74 . (canceled)
75 . The method of claim 72 , wherein the end stage heart failure is decompensated heart failure.
76 . The method of claim 72 , wherein the patient is a heart transplant candidate.
77 . The method of claim 72 , wherein the patient is a candidate for extracorporeal membrane oxygenation (ECMO).
78 . The method of claim 72 , wherein the patient is a candidate for a left ventricular assist device (LVAD).
79 . A method of improving cardiac function, blood pressure, organ perfusion, or a combination thereof, in a patient diagnosed with myocardial stunning after a cardiac transplant, the method comprising intravenously administering a lipid emulsion.
80 - 81 . (canceled)