Formulations of tegavivint and related compounds
Inventors
Dykstra, Steven David • Havel, Henry • Horrigan, Stephen • Harrison, Roger • Larson, Jeffrey • Northrup, Jonathan • Laslo, Theodore • Gwozdz, Garry
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12246010-B2
Publication Date
2025-03-11
Expiration Date
Abstract
Formulations of tegavivint and related compounds, methods of making such formulations and methods of treating various conditions utilizing such formulations.
Core Innovation
The invention relates to compositions comprising particles of a compound of Formula I, a poloxamer surfactant, sorbitol, and water, provided as an aqueous suspension. The composition is milled using roller milling or high energy milling until 90% of the particles are less than or equal to about 0.23 micrometers in diameter when measured using laser diffraction.
The Formula I compound and the poloxamer surfactant are present in the aqueous suspension, while sorbitol is provided in an aqueous solution that is added thereto. The document describes a nanosuspension approach for poorly soluble drug stabilization and mentions tegavivint (BC2059) and related Formula I compounds.
The document describes preparation feasibility including milling and optional lyophilization/sterilization considerations, using methods such as roller milling or high-energy milling. It contrasts the nanosuspension approach with failed or problematic alternatives such as microemulsion and liposome formulations, including issues described as toxicity, instability, or poor bioavailability for some routes.
Claims Coverage
The independent claim covers a composition defined by an aqueous milled nanosuspension of particles of a Formula I compound, together with a poloxamer surfactant and sorbitol, where milling is controlled by a laser diffraction particle-size criterion. The claim includes four inventive features: specific composition components, a defined milling approach, a particle-size threshold, and defined Formula I compound selection.
Milled aqueous suspension nanosuspension of Formula I compound with poloxamer surfactant and sorbitol
A composition comprising particles of a compound of Formula I, a poloxamer surfactant, sorbitol, and water, wherein the compound of Formula I and the poloxamer surfactant are provided in an aqueous suspension.
Roller milling or high energy milling with laser diffraction particle size limitation
The aqueous suspension is milled using roller milling or high energy milling until 90% of the particles are less than or equal to about 0.23 micrometers in diameter when measured using laser diffraction.
Sorbitol provided as an aqueous solution added to the suspension
Sorbitol is provided in an aqueous solution that is added thereto.
Formula I compound derivatives and selection of heterocycloalkyl substituents
The Formula I compound includes defined substituent selections and pharmaceutically acceptable salt, ester, amide, stereoisomer or geometric isomer forms thereof.
Overall, the claim coverage centers on an aqueous suspension composition containing Formula I compound particles, a poloxamer surfactant, and sorbitol, where roller milling or high energy milling produces particles meeting a laser diffraction criterion (90% ≤ about 0.23 µm), with sorbitol added as an aqueous solution; the Formula I compound is restricted to defined derivative forms.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
Interested in licensing this patent?