EMBOLIZING AGENT PRECURSOR PHARMACEUTICAL COMPOSITION
Disclosed herein are compositions and methods for an embolizing agent precursor. The embolizing agent precursor may include a gaseous component and a first stabilizer to stabilize the gaseous component, the first stabilizer may include a a polymer, and wherein a gas portion of the gaseous component is selected from the group consisting of sulphur hexafluoride and C3-6 perfluorocarbons. The embolizing agent precursor may further include an oil component which comprises a C1-7 hydrocarbon, a second stabilizer to stabilize the oil component, and a vaporous component configured to enlarge the gaseous component.
1 . An embolizing agent precursor pharmaceutical composition, comprising:
a gaseous component and a first stabilizer to stabilize the gaseous component, the first stabilizer comprising a polymer, and wherein a gas portion of the gaseous component is selected from the group consisting of sulphur hexafluoride and C 3-6 perfluorocarbons;
an oil component which comprises a C 1-7 hydrocarbon, a second stabilizer to stabilize the oil component, and a vaporous component configured to enlarge the gaseous component;
wherein individual embolizing agent precursors comprise a diameter in the range of 3 to 10 μm, and a circularity <0.9;
where the first stabilizer and the second stabilizer have a net electrostatic charge that is opposite to that of the other;
an effectual agent; and
wherein individual embolizing agent precursors are configured to increase in size and become lodged in the vasculature of a subject upon activation by high speed sound waves.
2 . The embolizing agent precursor pharmaceutical composition of claim 1 , wherein the effectual agent is provided alongside the embolizing agent precursor.
3 . The embolizing agent precursor pharmaceutical composition of claim 1 , wherein the effectual agent is present in the oil component.
4 . The embolizing agent precursor pharmaceutical composition of claim 1 , wherein the embolizing agent precursor is configured to increase in size when subjected to high speed sound waves of 1-10 MHz with an MI of between 0.2 to 0.4.
5 . The embolizing agent precursor pharmaceutical composition of claim 1 , wherein the gaseous component and the oil component are configured to be combined prior to formation of the embolizing agent precursor by mixing in vitro, thereby forming a composition stable over more than 1 hour.
6 . The embolizing agent precursor pharmaceutical composition of claim 1 , wherein the gas portion of the first component is selected from the group of perfluoropropane, perfluorobutanes, perfluoropentanes and perfluorohexanes.
7 . The embolizing agent precursor pharmaceutical composition of claim 1 , wherein the gaseous component comprises perfluorobutane as the gas portion, and the first stabilizer comprises hydrogenated egg phosphatidyl serine-sodium (HEPS-Na) membrane.
8 . The embolizing agent precursor pharmaceutical composition of claim 1 , wherein the oil component comprises perfluoromethyl-cyclopentane (pFMCP) and the second stabilizer comprises a 1,2-Distearoyl-sn-glycerol-3-phosphocholine (DSPC) membrane.
9 . The embolizing agent precursor of claim 1 , wherein the embolizing agent precursor comprises at least 5 million/ml or more embolizing agent precursors with individual embolizing agent precursors comprising a diameter of 5-10 μm.
10 . The embolizing agent precursor of claim 1 , wherein the embolizing agent precursor is configured to become enlarged when the vaporous component diffuses into the gaseous component, individual enlarged embolizing agent precursors configured to be deposited in a tumour microcirculation, thereby increasing tumour uptake of the therapeutic agent.
11 . The embolizing agent precursor of claim 10 , wherein the diameter of the enlarged embolizing agent precursor at least transiently increase to a diameter of 20 μm or more.