Methods of treating pancreatic and ovarian cancers 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-9839691-B2
Publication Date
2017-12-12
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 relates to cancer-treatment pharmaceutical formulations comprising a compound of Formula I together with triethanolamine and a pharmaceutically acceptable diluent. The compound of Formula I and triethanolamine are configured to form an ion pair, and the ion pair can function as an in situ salt bridge. The disclosed formulations are directed to therapeutically effective dosing and salt form behavior and ion exchange concepts.
In particular embodiments, the compound of Formula I is a lipoic acid derivative, including bis-benzyl lipoate such as 6,8-bis(benzylthio)octanoic acid. The disclosure includes a molar ratio relationship between the ion pairing agent and the lipoic acid derivative and specified ranges for the ion pair dosage level. The formulations include pharmaceutically acceptable diluents, including dextrose solutions and other IV-compatible excipients.
The disclosed therapeutic use focuses on cancer indications including pancreatic and ovarian cancer. The formulations are described in connection with selective killing of tumor cells, anti-tumor efficacy, in vitro viability comparisons, in vivo tumor volume reduction, and characterization of necrotic versus apoptotic death types. The formulations are also discussed with disruption of cancer metabolism and pathways associated with the Warburg Effect.
Claims Coverage
The claims coverage identifies one independent claim covering treatment of pancreatic or ovarian cancer using a pharmaceutical formulation where a Formula I compound and triethanolamine form an ion pair. Dependent claims mainly refine composition and dosage constraints and narrow the indication, with inventive-feature refinements focused on ratios, dosage level, diluent selection, dextrose concentration, and ovarian cancer use.
Ion-paired formula i with triethanolamine for pancreas or ovary cancer treatment
A method of treating a cancer of the pancreas or ovary by administering 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.
Ion pair composition ratio of triethanolamine to Formula I compound
Triethanolamine and the compound of Formula I are present in a ratio from 20:1 to 1:20.
Dosage level of the ion pair providing a Formula I amount
An ion pair is present at a dosage level providing 0.001 mg/m2 to 10 g/m2 of the Formula I compound upon administration to a patient.
Permitted pharmaceutically acceptable diluent selections
The diluent is chosen from saline, a sugar solution, alcohol, dimethylformamide, dimethylsulfoxide, dimethylacetamide, or combinations thereof.
Dextrose solution concentration by weight
A dextrose solution has a dextrose concentration by weight ranging from 2.5% to 10%.
Treatment of ovarian cancer
The method is applied to treating cancer of the ovary.
Overall, the claims coverage centers on administering a pancreas or ovary cancer treatment where a Formula I lipoic acid derivative and triethanolamine form an ion pair, with dependent refinements specifying triethanolamine:Formula I ratio limits, an ion-pair dosage level mapped to Formula I amount per m2, selected diluents including dextrose solutions with specified concentration, and narrowing to ovarian cancer.
Stated Advantages
Anti-tumor efficacy and cell-kill characterization are reported using in vitro viability comparisons and in vivo tumor volume reduction.
Necrotic versus apoptotic death types are characterized in connection with the triethanolamine-containing formulations versus sodium-salt formulations.
Selectively kill tumor cells by disruption of cancer metabolism and pathways associated with the Warburg Effect.
Documented Applications
Treating a cancer of the pancreas.
Treating a cancer of the ovary.
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