Methods of treating myeloma and lymphoma using compositions containing an ion pair of a lipoic acid derivative
Inventors
Shorr, Robert G. L. • RODRIGUEZ, ROBERT J. • BHASIN, RAJINDER
Assignees
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Publication Number
US-9872845-B2
Publication Date
2018-01-23
Expiration Date
Abstract
The invention provides a method of treating myeloma and lymphoma using a pharmaceutical composition containing a pharmaceutically acceptable diluent along with an ion pair formed by triethanolamine and a compound of Formula I:
Core Innovation
The disclosed invention relates to pharmaceutical formulations for treating cancers, including myeloma and lymphoma, using lipoic acid derivatives. The formulations include a compound of Formula I and triethanolamine, where the compound of Formula I and triethanolamine form an ion pair, and further include a pharmaceutically acceptable diluent.
The disclosure defines the lipoic acid derivative within Formula I and Formula II with variable R1 and R2 and includes options such as metal complexes. It presents therapeutic dosing ranges for the lipoic acid derivative and describes ion pair preparation in terms of an ion pairing molar ratio.
Mechanistic background links lipoic acid derivatives to altered cancer metabolism, including effects associated with PDH/PDC and Warburg-effect-related pathways, and reference is made to the tricarboxylic acid cycle. Experimental examples in H-460 xenograft mice describe a Tween 80/ethanol formulation as lacking anti-tumor effect, while formulation with TEA/dextrose (D5W) is associated with improved tumor growth inhibition.
Claims Coverage
The independent claim is directed to a method of treating a disease selected from myeloma and lymphoma by administering a therapeutically effective amount of a pharmaceutical formulation comprising a compound of Formula I, triethanolamine, and a pharmaceutically acceptable diluent in which the compound of Formula I and triethanolamine form an ion pair. The dependent claims refine the method by specifying disease subtype, molar ratio constraints, and diluent selection, including dextrose and a dextrose concentration range.
Treating myeloma or lymphoma with an ion-pair formulation
Administering to a patient in need thereof a therapeutically effective amount of a pharmaceutical formulation comprising a compound of Formula I, triethanolamine, and a pharmaceutically acceptable diluent, wherein the compound of Formula I and triethanolamine form an ion pair.
Myeloma treatment
The disease being treated is myeloma.
Specified molar ratio of Formula I compound to triethanolamine
The compound of Formula I and triethanolamine are present in a molar ratio between about 20:1 and about 1:20.
Diluents selected from a specified set
The pharmaceutically acceptable diluent is chosen from saline, a sugar solution, an alcohol, dimethylformamide, dimethylsulfoxide, dimethylacetamide, or combinations thereof.
Dextrose solution as diluent
The pharmaceutically acceptable diluent is a dextrose solution.
Dextrose solution with specified dextrose concentration
The dextrose solution has a dextrose concentration from about 2.5% to about 10% by weight.
Overall, the claim coverage focuses on an ion-pair pharmaceutical formulation using a compound of Formula I and triethanolamine to treat myeloma or lymphoma, with dependent claims further constraining the Formula I:triethanolamine molar ratio and restricting the diluent options, including dextrose solutions with specified dextrose concentration.
Stated Advantages
Improved tumor growth inhibition when formulated as TEA/dextrose (D5W) compared with a Tween 80/ethanol formulation described as lacking anti-tumor effect.
Documented Applications
Treatment of disease selected from myeloma and lymphoma in a patient in need thereof.
Xenograft mouse example using H-460 NSCLC xenograft mice to evaluate tumor growth inhibition associated with different formulations.
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