Pharmaceutical composition of chelating complex micelles
Inventors
Wang, Chau-Hui • Chen, Chia-Hung • Lin, Johnson • Chen, Jing-Yi • Liao, Wei-Chuan
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-9220786-B2
Publication Date
2015-12-29
Expiration Date
Abstract
This invention provides Chelating Complex Micelles as a drug carrier. The Chelating Complex Micelles can load drugs without changing their structure, and therefore extend the half-life of drugs in the human body. The chelating complex micelles contain a metal ion core, at least one polymer, and at least one drug molecule. The metal ion is considered as a Lewis acid while polymer chain and drug molecules are referred to as Lewis bases. The drug molecule is linked to the polymer via forming coordinate bonds with metal ion, and then self-assembled to form chelating complex micelles as a drug carrier.
Core Innovation
Chelating complex micelles (CCM) are described as a drug-carrier pharmaceutical composition formed by self-assembly in which a ligand-free metal Lewis acid core is combined with a chelating block copolymer and a drug Lewis base. The block copolymer includes a chelating segment and a dispersing segment, where poly(glutamic acid) (PGA) is the chelating segment and poly(ethylene glycol) (PEG) is the dispersing segment. The ligand-free metal ion core binds with the block copolymer and links the drug via coordinate bonding without covalent structural modification of the drug.
The described approach addresses the problem of improving drug half-life and reducing toxicity and adverse effects, particularly in the context of cancer therapy. The CCM platform is stated to enable loading of both hydrophilic and hydrophobic drugs, while maintaining the coordination-based drug linkage through Lewis acid/Lewis base interactions. Imaging and monitoring uses are also described as optional, using metal ions.
Metal ions used as the ligand-free metal Lewis acid core include Gd(III), Tc-99m, Ga-68, Re-188, and In-111, which support the stated optional imaging/monitoring functions. An embodiment is described using cytoprotective agents amifostine/WR-1065 with Fe2+ (FeCl2), including reported micelle size and polymer characterization. The in vitro release profile is described in which increased FeCl2 content and longer reaction time decrease amifostine release as measured by dialysis diffusion.
Claims Coverage
The document provides two independent claim coverages, each centered on chelating complex micelles as a pharmaceutical composition with a ligand-free metal ion core that links a drug to a PEG-b-PGA block copolymer by coordinate bonding. Each independent claim is further narrowed by dependent limitations that specify Lewis acid/base character, select particular metal ions, and restrict or enumerate drug selection criteria, including allowed drug lists and combinations.
Ligand-free metal ion core linking drug by coordinate bonding to PEG-b-PGA micelle
A pharmaceutical composition of chelating complex micelles comprising a poly(ethylene glycol)-b-poly(glutamic acid) (PEG-b-PGA) block copolymer with a PGA chelating segment as a ligand and a PEG dispersing segment, and a ligand-free metal ion core that binds with the block copolymer by the chelating segment and links a drug via coordinate bonding.
Lewis base block copolymer and Lewis base drug coordinated with ligand-free Lewis acid metal core
A pharmaceutical composition of chelating complex micelles comprising a Lewis base block copolymer comprising a chelating segment as a ligand and a dispersing segment, a drug containing Lewis base functional groups, and a ligand-free metal ion core where the ligand-free metal ion is a Lewis acid, the ligand-free metal ion core binds with the block copolymer and the drug by the coordinate bonds, and the block copolymer is poly(ethylene glycol)-b-poly(glutamic acid) (PEG-b-PGA) with PGA as the chelating segment and PEG as the dispersing segment.
Across both independent claims, the main inventive concept is the use of a ligand-free Lewis-acid metal ion core to coordinate-bond with a PEG-b-PGA block copolymer (PGA chelating segment and PEG dispersing segment) and to link a drug via coordinate bonding, with additional refinements specifying Lewis acid/base character, particular metal ions, and the selection or enumeration of permissible drug candidates and combinations.
Stated Advantages
Extend drug half-life.
Reduce toxicity and adverse effects.
Enable loading of hydrophilic and hydrophobic drugs.
Provide optional imaging/monitoring via metal ions.
Documented Applications
Cancer therapy context is described, including use of cytoprotective agents amifostine/WR-1065 in an embodiment with Fe2+ (FeCl2).
Optional imaging/monitoring is described using metal ions including Gd(III), Tc-99m, Ga-68, Re-188, and In-111.
Interested in licensing this patent?