Pharmaceutical formulations containing lipoic acid derivatives
Inventors
Shorr, Robert G. L. • RODRIGUEZ, ROBERT J. • BHASIN, RAJINDER
Assignees
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Publication Number
US-10098955-B2
Publication Date
2018-10-16
Expiration Date
Abstract
Pharmaceutical formulations containing lipoic acid derivatives and ion pairs thereof are described. The pharmaceutical formulations are useful in the treatment of medical disorders, such as cancer.
Core Innovation
The invention provides pharmaceutical formulations for treating cancer using lipoic acid derivative compounds of Formula I and/or Formula II, where the compounds include defined substituents and may be present as metal chelate/complexes. The formulations include at least one ion pairing agent that forms ion pairs or salt bridges with the lipoic acid derivative, and are described as including a therapeutically effective amount of a compound of Formula I or a salt thereof.
Ion pairing agents include mono- and dialkylamines, trialkylamines, amino-substituted aliphatic alcohols, amino-substituted heteroaliphatic alcohols, alkyldiamines and substituted alkyldiamines, heteroaryl amines, tertiary amines and related organic Bronsted bases, alkali metal hydroxides and alkaline earth metal hydroxides, and polymer-conjugated ion pairing agents. Specific examples include triethanolamine and other bases and polymeric ion pairing agents.
The pharmaceutical formulation is described with pharmaceutically acceptable diluents and intravenous aqueous compositions, including aqueous or polar solvents, saline, dextrose solution such as D5W, and formulations containing Tween80/ethanol/saline. The document reports anti-cancer performance including tumor cell viability and cell kill data across vehicle and salt or amine forms, tumor growth inhibition in an H-460 xenograft model, and therapeutically effective dosing expressed on an area basis for the compound of Formula I.
Claims Coverage
The independent claims are clm-00001 and clm-00019, and the claim set contains 2 independent claims. Across the independent claims, there are two main inventive feature themes: intravenous administration of a therapeutically effective amount of a Formula I compound or salt thereof, and inclusion of at least one ion pairing agent in the same pharmaceutical formulation.
Intravenous administration with Formula I compound and ion pairing agent
A method of treating a human patient with a cancer selected from carcinoma, sarcoma, myeloma, lymphoma, leukemia, and cancer of the pancreas by intravenously administering a pharmaceutical formulation comprising a therapeutically effective amount of a compound of Formula I and at least one ion pairing agent.
Formula I compound or salt thereof with ion pairing agent
A method of treating a human patient with a cancer selected from carcinoma, sarcoma, myeloma, lymphoma, leukemia, and cancer of the pancreas by intravenously administering a pharmaceutical formulation comprising a therapeutically effective amount of a compound of Formula I or a salt thereof, and at least one ion pairing agent.
Both independent claims cover treating a selected cancer by intravenously administering a pharmaceutical formulation that contains a therapeutically effective amount of a compound of Formula I or a salt thereof together with at least one ion pairing agent. Dependent claims refine the ion pairing agent selection, the molar ratio constraint between ion pairing agent and Formula I, and quantitative dose ranges.
Stated Advantages
Alters tumor metabolism or signaling in the context of cancer, including effects referenced with the Warburg Effect and PDH/PDC complex.
Produces reported biological efficacy metrics including viability reduction in A2780 tumor cells.
Produces tumor growth inhibition in an H-460 xenograft model.
Documented Applications
Treating cancers selected from carcinoma, sarcoma, myeloma, lymphoma, leukemia, and cancer of the pancreas in human patients using intravenous pharmaceutical formulations comprising Formula I compounds and ion pairing agents.
Therapeutic application to microbial infections, including bacterial, yeast, fungal, and eukaryotic pathogens.
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