Anti-Inflammatory And Antioxidant Conjugates Useful For Treating Metabolic Disorders

Abstract

The present invention is directed to methods for treating metabolic disorders with compounds that are conjugates. The conjugates of the present invention are comprised of salicylic acid, triflusal, diflusinal, salsalate, IMD-0354, ibuprofen, diclofenac, licofelone, or HTB, and one or more antioxidants.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation of U.S. patent application Ser. No. 12 / 724,829, which claims the benefit of U.S. Provisional Patent Application Ser. No. 61 / 160,642, filed Mar. 16, 2009; U.S. Provisional Patent Application Ser. No. 61 / 177,958, filed May 13, 2009; and U.S. Provisional Patent Application Ser. No. 61 / 227,620 filed Jul. 22, 2009. Each of the above-referenced applications is hereby incorporated herein by reference in its entirety.BACKGROUND[0002]Oxidative stress and inflammation are implicated in the pathogenesis of metabolic diseases, diabetes, obesity, dyslipidemia and their associated cardiovascular complications. For example, oxidative stress is a common pathogenic factor leading to insulin resistance,β-cell dysfunction, impaired glucose tolerance, and type 2 diabetes mellitus. With regard to inflammation, clinical studies suggest that acute hyperglycemia results in elevated levels of circulating inflammatory cytokines s...

AI Technical Summary

Benefits of technology

The present invention provides compounds and pharmaceutical compositions that have additive or synergistic effects in treating various disorders such as diabetes, cardiovascular diseases, and inflammatory disorders. These compounds can also protect pancreatic β-cells and reduce the risk of gastric bleeding and tinnitus associated with other drugs. The compounds can also be used to reduce free fatty acids, triglycerides, advanced glycated end products, ROS, lipid peroxidation, tissue and plasma TNFα and IL6 levels, or delay or prevent cardiovascular complications associated with atherosclerosis.

Problems solved by technology

However, while cells have a number of available anti-oxidant mechanisms, damage most likely occurs when the ROS is excessive and / or anti-oxidant pathways are overwhelmed as is frequently the case in diabetes.

The consequence of limited scavenging systems is that ROS concentration in β-cells may increase rapidly, damaging the β-cells.

Also, high doses of salicylic acid lower blood glucose levels.

However, at this high dose, side effects, such as tinnitus, are enhanced by 66% and the long term risk of gastric bleeding and ulceration is also increased.

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