Reduction in complement activation and inflammation during tissue injury by carotenoids, carotenoid analogs, or derivatives thereof

Abstract

Administering water-soluble or dispersible synthetic analogs or derivatives of astaxanthin, lutein, zeaxanthin, or lycophyll and/or other carotenoids to a subject may reduce some of the adverse effects of inflammation in a body organ or tissue. The analogs or derivatives may be incorporated into pharmaceutical, over-the-counter, or nutraceutical preparations. Administration of the analogs or derivatives described herein may reduce deposition of inflammatory mediators such as C-reactive protein, complement system proteins or the membrane attack complex (MAC) in tissues. Reduced deposition of these molecules in tissues may reduce cell damage and/or lysis in the tissues.

Description

CROSS REFERENCE TO RELATED APPLICATION [0001] This application claims the benefit of priority under 35 U.S.C. § 119(e) to Provisional Patent Application Ser. No. 60 / 666,119, filed Mar. 29, 2005, entitled “REDUCTION IN COMPLEMENT ACTIVATION AND INFLAMMATION DURING TISSUE INJURY BY CAROTENOIDS, CAROTENOID ANALOGS, OR DERIVATIVES THEREOF.” The prior application is commonly assigned with the present invention, and the contents thereof are incorporated by reference in their entirety as though fully set forth herein.BACKGROUND OF THE INVENTION [0002] 1. Field of the Invention [0003] The present invention generally relates to the fields of medicinal and synthetic chemistry. Specifically, the invention relates to the synthesis and use of water-soluble and water-dispersible carotenoids, including analogs, derivatives, and intermediates thereof, as therapeutic and / or prophylactic anti-inflammatory and anti-oxidant agents that reduce tissue damage associated with inflammation. [0004] 2. Descri...

AI Technical Summary

Benefits of technology

[0040] Certain embodiments may further directed to pharmaceutical compositions including combinations two or more structural carotenoid analogs or derivatives. Embodiments directed to pharmaceutical compositions may further include appropriate vehicles for delivery of said pharmaceutical composition to a desired site of action (i.e., the site a subject's body where the biological effect of the pharmaceutical composition is most desired). Pharmaceutical compositions including injectable structural carotenoid analogs or derivatives of astaxanthin, lutein or zeaxanthin may be particularly advantageous for the methods described herein. In yet a further embodiment, an injectable astaxanthin structural analog or derivative may be administered with a astaxanthin, zeaxanthin or lutein structural analog or derivative and / or other carotenoid structural analogs or derivatives, or in formulation with antioxidants and / or excipients that further the intended purpose. In some embodiments, one or more of the astaxanthin, lutein or zeaxanthin structural analogs or derivatives are water-soluble.

Problems solved by technology

The evolving paradigm suggests that in the normal, healthy adult any elevations of CRP in the absence of acute infection or acute tissue injury can potentially be deleterious; indeed, in umbilical cord blood levels are very low (<0.01 mg / dl).

Problems related to the use of some prior art carotenoids and structural carotenoid analogs or derivatives include: (1) the complex isomeric mixtures, including non-carotenoid contaminants, provided in natural and synthetic sources leading to costly increases in safety and efficacy tests required by such agencies as the FDA; (2) limited bioavailability upon administration to a subject; and (3) the differential induction of cytochrome P450 enzymes (this family of enzymes exhibits species-specific differences which must be taken into account when extrapolating animal work to human studies).

Images