Methods for treating cancer using 6,8-bis (benzylthio) octanonic acid
Inventors
Shorr, Robert G. L. • RODRIGUEZ, ROBERT J. • BHASIN, RAJINDER
Assignees
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Publication Number
US-10391177-B2
Publication Date
2019-08-27
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 describes pharmaceutical compositions of lipoic acid derivatives, including 6,8-bis(benzylthio)octanoic acid (CPI-613), formulated as ion pairs with an ion pairing agent to enable solubilization and administration. The compositions include therapeutically effective amounts of 6,8-bis(benzylthio)octanoic acid or an ion pair thereof together with a pharmaceutically acceptable diluent, including pharmaceutically acceptable aqueous diluents.
A key aspect is solubilization via ion pairing or ion exchange to form salts, including characterization that different ion pairing agents can produce different forms and corresponding biological effects. The disclosure includes ion pairing agent examples and salt forms, including triethanolamine, alkali metal hydroxides, sodium, potassium, and ammonium salts.
The disclosure also connects the formulation concept to disrupting cancer-related metabolic processes, including the Warburg Effect and pyruvate dehydrogenase (PDH) / pyruvate dehydrogenase complex (PDC)-related metabolism. It further characterizes biological performance of the formulations, including in vitro cell viability and cell kill thresholds for A2780 and BXPC3 cells and in vivo tumor reduction statements.
Claims Coverage
The independent claims cover intravenous treatment methods using 6,8-bis(benzylthio)octanoic acid or an ion pair thereof formulated with a pharmaceutically acceptable diluent for solubilizing the active. Across the independent claims, the inventive features focus on the active ingredient, the intravenous administration route, the therapeutically effective amount, and the diluent type, including an aqueous diluent variant.
Intravenous cancer treatment with 6,8-bis(benzylthio)octanoic acid or an ion pair thereof and a pharmaceutically acceptable diluent for solubilizing
Treating cancer selected from carcinoma, sarcoma, myeloma, lymphoma, leukemia, a mixed type thereof, and a cancer of the pancreas in a human patient in need thereof by intravenously administering a pharmaceutical composition comprising a therapeutically effective amount of 6,8-bis(benzylthio)octanoic acid or an ion pair thereof, and a pharmaceutically acceptable diluent for solubilizing 6,8-bis(benzylthio)octanoic acid or an ion pair thereof.
Intravenous cancer treatment with aqueous-solubilized 6,8-bis(benzylthio)octanoic acid or an ion pair thereof
Treating carcinoma, sarcoma, myeloma, lymphoma, leukemia, or a mixed type thereof, or a cancer of the pancreas in a human patient in need thereof by intravenously administering a pharmaceutical composition comprising a therapeutically effective amount of 6,8-bis(benzylthio)octanoic acid or an ion pair thereof, and a pharmaceutically acceptable aqueous diluent for solubilizing 6,8-bis(benzylthio)octanoic acid or an ion pair thereof.
Overall, the claim set defines intravenous therapeutic treatment of specified human cancers using 6,8-bis(benzylthio)octanoic acid or an ion pair thereof, with solubilization achieved by a pharmaceutically acceptable diluent, including an expressly pharmaceutically acceptable aqueous diluent variant.
Stated Advantages
Different ion pairing agents can produce different forms and corresponding biological effects.
The formulations are characterized by in vitro cell viability and cell kill thresholds for A2780 and BXPC3 cells.
The formulations are characterized by in vivo tumor reduction statements.
The disclosure compares necrotic versus apoptotic cell death depending on the ion pairing agent.
Documented Applications
Intravenously treating human cancer selected from carcinoma, sarcoma, myeloma, lymphoma, leukemia, a mixed type thereof, and a cancer of the pancreas, using a pharmaceutical composition comprising 6,8-bis(benzylthio)octanoic acid or an ion pair thereof with a pharmaceutically acceptable diluent for solubilizing.
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