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 method of treating systemic drug toxicity in a subject in need thereof, the method comprising intravenously administering to the subject 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, water, wherein particles of the lipid emulsion have an average particle diameter of about 200 nm to about 250 nm.
2 . The method of claim 1 , wherein the composition comprises about 24 percent (w/v) lipid.
3 . The method of claim 1 , wherein at least 50% of the particles have a particle diameter less than 250 nm.
4 . The method of claim 1 , wherein at least 60% of the particles have a particle diameter less than 250 nm.
5 . The method of claim 1 , wherein at least 70% of the particles have a particle diameter less than 250 nm.
6 . The method of claim 1 , wherein at least 75% of the particles have a particle diameter less than 250 nm.
7 . The method of claim 1 , wherein at least 50% of the particles have a particle diameter of about 240 nm or less.
8 . The method of claim 1 , wherein at least 50% of the particles have a particle diameter of about 230 nm or less.
9 . The method of claim 1 , wherein the average particle diameter of the composition changes by 25% or less following storage at 25° C. for 3 months.
10 . The method of claim 1 , wherein the particles in the lipid emulsion have an average particle diameter of about 210 nm to about 240 nm.
11 . The method of claim 1 , wherein the particle size standard deviation is about 150 nm or less.
12 . The method of claim 1 , wherein the particle size standard deviation is about 75 nm or less.
13 . The method of claim 1 , wherein the particle size standard deviation is about 25 nm or less.
14 . The method 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.
15 . The method 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.
16 . The method 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.
17 . The method of claim 1 , wherein the lipid emulsion composition further comprises an inotrope.
18 . The method of claim 17 , wherein the inotrope is selected from the group consisting of insulin, glucose, levosimendan, epinephrine, neosynephrine, norepinephrine, dobutamine, dopamine, and combinations thereof.
19 . A method of treating severe hypotension in a subject in need thereof, the method comprising intravenously administering to the subject 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, water, wherein particles of the lipid emulsion have an average particle diameter of about 200 nm to about 250 nm.
20 . A method of treating an ischemia/reperfusion injury in a subject in need thereof, the method comprising intravenously administering to the subject 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, water, wherein particles of the lipid emulsion have an average particle diameter of about 200 nm to about 250 nm.