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
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Publication Number
US-11266637-B2
Publication Date
2022-03-08
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 a composition comprising tegavivint, or a pharmaceutically acceptable salt, ester, amide, stereoisomer or geometric isomer thereof, formulated as a nanosuspension. The nanosuspension contains particles of tegavivint or the stated pharmaceutically acceptable derivatives having an effective D50 of less than or equal to 500 nm and an effective D90 of less than or equal to 1.0 micrometer when measured using laser diffraction. The composition further includes 25 mg/ml tegavivint or derivative with 0.625% Poloxamer 188 and 10% sorbitol, where the percentages are by weight of the composition.
The invention also provides a process for preparing the stated composition, including mixing particles of tegavivint or derivative with a Poloxamer 188 surfactant and an acceptable carrier to produce a suspension, milling the suspension using roller milling or a high energy mill, and adding sorbitol to the milled particles. The process is defined to produce a formulation having 25 mg/ml tegavivint or derivative, 0.625% Poloxamer 188, and 10% sorbitol, and to require the resulting nanosuspension particles to meet the specified D50 and D90 limits measured using laser diffraction.
The described composition scope includes formulation into multiple dosage forms and routes, including inhalation and parenteral administration, and the formulation may include tablets, capsules, and various release-modified formulation types. The disclosed therapeutic context includes use for cancer and tumor metastasis and for fibrotic diseases, including enumerated fibrotic, scarring, or wound-healing-related conditions. Related aspects include preparation refinements such as milling and LyoCell technology and stabilization-related refinements such as long-term stability.
Claims Coverage
Two independent claims are provided, one directed to a nanosuspension composition with specific weight percentages and particle size limits, and one directed to a process of preparing that composition using surfactant mixing, roller or high energy milling, and sorbitol addition, followed by nanosuspension particle size limitations measured by laser diffraction. Across these independent claims, the inventive coverage centers on the defined tegavivint nanosuspension composition and its process preparation route.
Tegavivint nanosuspension composition with specified surfactant and polyol and laser diffraction particle size limits
A composition comprising 25 mg/ml of tegavivint or a pharmaceutically acceptable salt, ester, amide, stereoisomer or geometric isomer thereof, 0.625% Poloxamer 188, and 10% sorbitol, wherein tegavivint or the pharmaceutically acceptable derivative is in the form of a nanosuspension having an effective D50 of less than or equal to 500 nm and D90 of less than or equal to 1.0 micrometer when measured using laser diffraction, and wherein the percentages are by weight of the composition.
Process using Poloxamer 188 mixing, roller or high energy milling, and sorbitol addition to produce the specified nanosuspension formulation
A process of preparing a composition comprising mixing particles of tegavivint or a pharmaceutically acceptable salt, ester, amide, stereoisomer or geometric isomer thereof with a Poloxamer 188 surfactant and an acceptable carrier to produce a suspension, roller milling or using a high energy mill to mill the suspension, and adding sorbitol to the particles to produce a formulation comprising 25 mg/ml of tegavivint or the pharmaceutically acceptable derivative, 0.625% Poloxamer 188, and 10% sorbitol, wherein tegavivint or the pharmaceutically acceptable derivative is in the form of a nanosuspension having an effective D50 of less than or equal to 500 nm and D90 of less than or equal to 1.0 micrometer when measured using laser diffraction, and wherein the percentages are by weight of the composition.
The independent claims collectively cover a defined tegavivint nanosuspension composition with specific weight percentages of Poloxamer 188 and sorbitol and nanosuspension particle size limits by laser diffraction, and a defined preparation process that mixes tegavivint particles with Poloxamer 188 and carrier, mills by roller milling or high energy milling, adds sorbitol, and results in the nanosuspension formulation meeting the specified D50 and D90 particle size limits.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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