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Azelaic acid esters in the treatment of insulin resistance

A technology of insulin resistance and diethyl azelate, applied in the field of treatment, prevention and/or reduction of insulin resistance of subjects, and treatment of insulin resistance, can solve problems such as non-progressive nature and potential causes of insulin resistance

Active Publication Date: 2019-01-11
NEW FRONTIER LABS LLC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] No existing T2D drugs address the progressive nature of the disease and underlying causes, insulin resistance

Method used

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  • Azelaic acid esters in the treatment of insulin resistance
  • Azelaic acid esters in the treatment of insulin resistance
  • Azelaic acid esters in the treatment of insulin resistance

Examples

Experimental program
Comparison scheme
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Embodiment 1

[0072] This example describes the preparation and characterization of glutaric acid esters.

[0073] Synthesized from azelaic acid and the corresponding alcohols (methyl, ethyl, propyl, isobutyl, 1-, 2- and 3-pentyl, and cyclohexyl) using standard acid-catalyzed esterification followed by fractional distillation Azelate esters to produce: Dimethyl Azelate (DMA), Diethyl Azelate (DEA), Diisopropyl Azelate DIPA, Diisobutyl Azelate (DiBU), Azela Di(1-pentyl) azelate (D1PA), di(2-pentyl) azelate (D2PA), di-(3-pentyl) azelate (D3PA) and dicyclohexyl azelate (DCHA ). These compounds may further be collectively referred to as "azelacates".

[0074] In Silico Toxicity Analysis : Derek™ for Windows_11.0.0 (Lhasa Ltd, UK) was used for prediction of toxicity of azelaic acid esters to bacterial and mammalian species. No azelate toxicity was predicted.

[0075] Genotoxicity Ames test : The potential toxicity of azelate was examined using ChromoTest S9 Activase (EBPI, Canada). Azel...

Embodiment 2

[0085] Human clinical trial of safety and tolerability of diethyl azelate

[0086] Purpose

[0087] To evaluate the safety and tolerability of diethyl azelate (immediate release form) when administered orally to insulin-resistant adult male volunteers and to evaluate the Changes from baseline and calculated indices of metabolic disorders of selected biomarkers upon administration of diethyl azelate.

[0088] subjects

[0089] A total of eight subjects were screened, four of whom met all eligibility criteria. Three healthy male volunteers aged 18-50 years and weighing 80-120 kg were recruited in this study. At screening, subjects were nondiabetic insulin resistant (NDIR) with fasting blood glucose greater than 75 mg / dL and less than 126 mg / dL and had compensated hyperinsulinemia with blood glucose collected between 10 and 30 minutes apart Average of two consecutive fasting insulin samples greater than 12 μIU / mL. Subjects had no clinically significant disease that could aff...

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Abstract

A method of treating insulin resistance includes administering to a subject a pharmaceutical composition comprising diethyl azelate. For example, a method of treating insulin resistance includes orally administering to a subject a pharmaceutical composition that includes diethyl azelate at a dosage range from about 0.1 mg / kg / day to about 10 mg / kg / day.

Description

[0001] related application [0002] This application claims priority to U.S. Provisional Patent Application No. 62 / 325,381, filed April 20, 2016. The entire contents of the foregoing applications are hereby incorporated by reference in their entirety. technical field [0003] The present disclosure relates to methods for treating insulin resistance. In particular, the present disclosure relates to methods for treating, preventing and / or reducing insulin resistance in a subject. Background technique [0004] Insulin resistance is generally defined as the inability of the body's cells to respond to insulin. Inefficient insulin function affects skeletal muscle, liver and fat cells. The pancreas releases insulin, usually after meals, to help transport glucose to the body's cells, where it is needed for energy. Since cells must have glucose to survive, when a state of insulin resistance is present, the body compensates by producing more insulin. This results in high levels o...

Claims

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Application Information

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IPC IPC(8): A61K31/23A01N37/02A01N37/06
CPCA61K31/23A61K9/0019A61K9/0053A61K45/06A61P3/08A61P3/10A61P43/00A61K2300/00A61P3/00A61K31/155A61K31/225A61K31/337A61K31/573
Inventor 罗伯特·T·斯特里佩尔埃尔兹别塔·伊兹比卡
Owner NEW FRONTIER LABS LLC