BHB liposomes and preparation methods thereof
Among others, the present invention provides a liposome comprising an active ingredient and one membrane or one inner membrane and one outer membrane. Each membrane comprises a plurality of lipid molecules, and the active ingredient is entrapped inside the interior space defined by the membrane or the inner membrane, or embodied in the membrane or membranes and form a part of the membrane(s).
1 . A liposome comprising an active ingredient and one 1, membrane, or one inner membrane and one outer membrane, wherein the one membrane or each of the inner and outer membranes defines an interior space within the one membrane or the inner membrane, and/or between the inner and outer membranes, each membrane comprises a plurality of lipid molecules, and the active ingredient is entrapped inside the interior space or embodied in the membrane or membranes;
wherein the active ingredient comprises β-hydroxybutyrate acid (BHB), a physiologically acceptable salt, ester, or mixture thereof;
the liposome has a reverse vesicle structure, composed of a bilayer with the hydrophilic head groups facing the inside of the bilayer surrounding a nonpolar core with the hydrophobic tails facing both the core and the exterior of the liposome, and the active ingredient is embodied in a lipid bilayer membrane and forms a part of the lipid bilayer membrane;
wherein the active ingredient has a mass percentage ranging from 1% to 95% of the liposome's total mass;
wherein the lipid molecules include phospholipid and has a mass percentage from 1% to 40% of the liposome's total mass;
and wherein the liposome further comprises: a co-emulsifier has a mass percentage ranging from 1% to 40% of the liposome's total mass;
a stabilizer has a mass percentage ranging from 1% to 40% of the liposome's total mass; and
water has a mass percentage ranging from 0.01% to 10% of the liposome's total mass.
2 . The liposome of claim 1 , wherein the active ingredient is free acid form of BHB.
3 . The liposome of claim 1 , wherein the BHB, physiologically acceptable salt, or ester thereof is a mixture of R- and S-enantiomers.
4 . The liposome of claim 1 , wherein the active ingredient further comprises one or more additional hydrophilic components.
5 . The liposome of claim 1 , wherein the phospholipid comprises phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, lysophosphatidylcholine, lysophosphatidylethanolamine, dipalmitoyl phosphatidylcholine, dioleoyl phosphatidylcholine, dilinoleoyl phosphatidylcholine, distearoyl phosphatidylcholine, or a combination thereof.
6 . The liposome of claim 1 , wherein the co-emulsifier comprises polyethylene glycol 200-2000, glycerol, sorbitol, or a combination thereof.
7 . The liposome of claim 1 , wherein the stabilizer comprises medium-chain fatty acid glyceride, soybean oil, sunflower oil, or a combination thereof.
8 . The liposome of claim 1 , wherein the BHB, physiologically acceptable salt, or ester thereof is an R-enantiomer or an S-enantiomer.
9 . A method for increasing or sustaining blood ketone level in a subject in need thereof, comprising administrating to the subject the BHB liposome of claim 1 .