The free radicals induced damage to mammalian tissues is believed to contribute the aging process and to the development of several degenerative diseases. (Canfiel LM et al. Carotenoids as cellular antioxidants. Proc Soc Exp Biol Med 1992; 200: 260-265).
The reactive free radicals react with polyunsaturated fatty acids (PUFA) of the membrane lipids and initiate the lipid peroxidation. The excessive lipid peroxidation caused by the free radicals leads to a condition of oxidative stress, which results in the accumulation of malondialdehyde (MDA). Oxidative stress leads to a variety of diseases.
Carotenoids are naturally occurring xanthophylls in plants that are involved in light harvesting reactions and protection of plant organelles against singlet oxygen induced damage. Dietary carotenoids serve as antioxidants in the tissues (Thurnham DL. Carotenoids: function and fallacies. Proc Nutr Soc 1994; 53: 77-87) and protect the body from oxidative damage. Mammalian species do not synthesize carotenoids and therefore these have to be obtained from dietary sources such as fruits and vegetables and or dietary supplements. Numerous epidemiological studies support a strong inverse relationship between consumption of carotenoid rich fruits and vegetables and incidence of degenerative diseases (Coleman H, Chew E. Nutritional supplementation in age-related macular degeneration. Curr Opin Ophthalmol 2007; 18(3): 220-223)
Xanthophylls can show both optical (R-and S-stereo isomers) and geometrical isomers (trans, E- and cis, Z-). The conformation of R- and S-stereo isomers is based on CD spectral and chiral column HPLC studies while the conformation of cis- and trans-isomers is based on electronic, infrared, NMR, HPLC-MS and HPLC-NMR on-line spectroscopy studies. It is well known that when an organic molecule has a carbon atom with four different types of atoms or groups attached to it, that carbon atom is designated as chiral carbon atom. The chiral carbon atom is responsible for two different spatial arrangements leading to the formation of optical isomers while the number of double bonds of the polyene chain and the presence of a methyl group and the absence of steric hindrance decide the number of trans- and cis-isomers. In the case of trans-zeaxanthin, the carbon atoms at 3 and 3′ positions in the two end rings are both chiral atoms.
Thus, trans-zeaxanthin has two chiral centers at the carbon atoms C3 and C3′, based on the positions of the secondary hydroxy groups attached to them. Therefore, there are four possible stereo isomers of trans-zeaxanthin namely, (3R-3′R)-isomer, (3S-3′S)-isomer and (3R-3′S)- or (3S-3′R)-isomer. In these isomers (3R-3'S)-& (3S-3′R)- are identical. Thus, there are three chiral isomers of trans-zeaxanthin. The isomer causing rotation of polarized light in a right handed manner is called R-stereo isomer, the isomer causing left handed rotation S-stereo isomer and the third isomer possessing a twofold opposite effects (R,S; optically inactive) which is called meso-form of zeaxanthin. The structural formulae of lutein, (R,R)-zeaxanthin and (R,S)-meso zeaxanthin are given below in Fig. 1

Lutein, (R,R)-zeaxanthin and (R,S)-zeaxanthin are the only macular carotenoids and due to their extended conjugated structure have been shown to produce significant antioxidant potential and protect the oxidative damage induced by singlet oxygen produced by ultra violet light. Intake of foods rich in lutein and zeaxanthin is related to increased level of these carotenoids in the serum as well as in the macula. Lutein and (R,R)-zeaxanthin can be derived from fruits and vegetables while (R,S)-zeaxanthin from sea foods or dietary supplements or from bio conversion of lutein within the body.
The conjugated double bonds of lutein and zeaxanthin contribute to the distinctive colors of each pigment, and also influence the ability of these to quench singlet oxygen. Due to the extra conjugated double bond, zeaxanthin is believed to be a stronger anti-oxidant compared to lutein.
Regarding the location of xanthophylls at a cellular level, they are reported to be bound to specific proteins referred to as xanthophylls binding protein (XBP). The XBP is suggested to be involved in the uptake of lutein and zeaxanthin from the blood stream and stabilization of the same in the retina. The study of xanthophylls and XBP by femto-second transient absorption spectroscopy showed better stability for (3R,3′S)-zeaxanthin enriched XBP compared to (3R,3′R)-zeaxanthin while the photo physical properties of the xanthophylls: (3R,3′R)-zeaxanthin and (3R,3′S,meso)-zeaxanthin are generally identical. It is likely that the meso-zeaxanthin is better accommodated with XBP wherein the protein protects the xanthophylls from degradation by free radicals. Thus, the complex may be a better antioxidant than the free xanthophylls, facilitating improved protection of ocular tissue from oxidative damages. (Billsten et al., Photophysical Properties of Xanthophylls in Caroteno proteins from Human Retina, Photochemistry and Photobiology, 78, 138-145, 2003)
Lutein and zeaxanthin occur naturally in trans-isomeric form in fruits, vegetables and flowers (marigold). Because of the processing conditions due to heat and light, a small percentage of trans-form is converted into cis-isomeric form. Therefore, the preferred bio-available form is trans-isomeric as evidenced from the data of geometric isomers compositional analysis of human plasma. (Khachik et al., Isolation and Structure Elucidation of Geometric Isomers of Lutein, Zeaxanthin in Extracts of Human Plasma, J. Chrom. 582, 153-156, 1992). In view of this, it is desirable to use the trans-isomeric form of lutein and zeaxanthin as (R,R)-(R,S)-in dietary supplements.
Neurodegenerative disorders are associated with progressive loss of structure or functions of neurons eventually leading to their death. Parkinson's disorder is the most common form of neurodegeneration. In Parkinson's, neurodegeneration occurs due to deposition of protein residues like alpha-synnuclein. This kind of abnormal deposition triggers oxidative stress and inflammatory reactions causing apoptosis and leading to neuronal cell death.
Parkinson's disorder is a cause of loss of dopaminergic neurons and characterized by rigidity, tremors, akinesia, tongue chewing and loss of cognitive function and memory loss after some period of time. The number of US cases of Parkinson's disorder was found to be 340,000 in 2005, and is predicted to rise to 610,000 by 2030.
Drugs available for Parkinson's disorder provide only symptomatic relief, but they cannot reverse or stop the progression of the disease. Various naturally occurring antioxidants like epigallocatechin gallate (green tea antioxidant) have shown promising activity in seizing the progression of disease. Hence, it is interesting to search the effects of naturally occurring antioxidants as nutritional supplement for preventive treatment of Parkinson's disorder.
The lipophilic nutrients are poorly absorbed if administered either as oil suspensions or as beadlets, which are the currently used forms. The main reason for poor absorption is their poor solubility in water. Due to their insolubility their bioavailability is very poor. Lipophilic nutrients have limited absorption in the body due to limited solubility in the gastrointestinal tract. Generally, the bioavailability of such nutrients is below 40%. The bioavailability can be enhanced by reducing the particle size, which in turn will enhance their efficiency of micellization. Dispersion of nutritional products at molecular level is generally regarded as a technique of reducing the particle size. Such molecular dispersions provide higher efficiency for micellization of nutrients in water and thereby increase the bioavailability.
The molecular dispersions of lipophilic nutrients can be obtained by dispersing the solution of lipophilic nutrient in a polar or non polar organic solvent certain water soluble hydrophilic solid or liquid carrier systems. Upon removal of solvent under vacuum, the resultant dispersion remains as a homogenous liquid or solid dispersions which is suitable for filling in to soft gel capsules or in to licaps, tablets, capsules and other oral solid or liquid preparations. Because of such dispersions, the absorption of lipophilic nutrients can be enhanced several folds. The said technology is protected by the Applicant under granted patent number IN253078.