ITMI940893A1 - DIETARY SUPPLEMENT FOR THE PREVENTION AND TREATMENT OF CATARACT - Google Patents

Description

Description of an invention entitled:

"DIETARY SUPPLEMENT FOR THE PREVENTION AND TREATMENT OF CATARACT"

The present invention relates to a dietary composition containing vitamins, amino acids and trace elements to be administered as a therapeutic aid in the prevention and treatment of cataracts.

Cataract is a pathology characterized by the opacification of the lens.It currently represents the main cause of blindness in Europe and in the Third World countries and, due to the increase in the average age, the percentage of the population affected by this disabling disease is destined to increase from year to year.

Surgical extraction of the lens is the only resolutive therapy, but recent acquisitions regarding the biochemical aspects of the pathogenesis of cataracts lead to an attempt to identify non-surgical therapies aimed at preventing or slowing down the opacification process.

The opacification of the lens is essentially due to the formation of high molecular weight protein aggregates and intermolecular disulfide bridges (Hoenders HJ, Bloemendal H, "Modifications du métabolism des protéins en cours du viellissement - Viellissement du cristalline - Symposium International sur le cristallin Ed . Hockwin 0. - Strasbourg, 1982).

The origin of the oxidative insult is represented by highly reactive forms of oxygen that are generated spontaneously in cellular metabolic processes and by photochemical oxidation processes that occur during vision.

The oxygen contained in the aqueous humor undergoes a reduction process at the crystalline level with the formation of water, but during this reaction various toxic products can be formed such as free radicals, superoxides, hydrogen peroxide.

Even light radiations can induce the formation of oxidizing free radicals through the photoxidation of the chromophores of proteins

It is therefore possible to identify in oxidation the main cause of the structural alterations of the proteins of the lens (Varma SD, Sharma YR, Kuck JF, Richards RD - Oxidative stress on lens and cataract formation: role of light and oxygen: Curr Eye Res 3 (l ): 35-37, 1984).

The oxidizing agents cause, in turn, the oxidation of the thiol residues of the proteins with the formation of disulfide bridges that cause their precipitation, in addition to the peroxidation of the lipids of the epithelial cell membranes with alteration of the normal processes of transport of the metabolites from the mood aqueous to crystalline (Varma SD, Srivastava VK, Richards RD - Photoperoxidation in lens and cataract formation: preventive role of superoxide dismutase, catalase and Vitamin C -Ophtalmic Res. 14: 167-175, 1982).

Normally the lens defends itself from oxidative insults by means of enzymatic and non-enzymatic systems: however, both systems decrease over time their activity and therefore the antioxidant capacity of the lens itself.

The main protection system consists of the glutathione redox cycle and the enzymes involved in it. Hydrogen peroxide, the metabolic product of numerous cellular reactions, is also reduced by enzymatic (catalase and glutathione peroxidase) and non-enzymatic (pyruvate) systems.

Glutathione directly reduces hydrogen peroxide by means of glutathione peroxidase, an enzyme with a selenium atom in the active site.

It also acts as a sulfhydryl buffer to maintain the cysteine residues of the proteins in the reduced state: It performs its function by alternately passing from the reduced to the oxidized form in which two tripeptide residues are linked together by a disulfide bridge.

The reduced form is then restored by glutathione reductase, a flavoprotein that uses NADPH as an electron source.

NADPH is continuously generated by glucose-6-phosphate dehydrogenase in the hexose monophosphate shunt. The production of NADPH and the reduction of the oxidized form of glutathione are coupled energetically by the reduction of ascorbate.

The dehydroascorbate / ascorbate pair is able to facilitate the transfer of electrons from NADPH to oxygen without the intervention of enzymes with the oxidized glutathione / reduced glutathione pair acting as an intermediate.

The ascorbate then accelerates the utilization of glucose in the lens through a shunt stimulation of the hexose monophosphate (Varma SD, Bauer SA, Richards RD. Exose monophosphate shunt in rat lens: stimulation by Vitamin C, Invest. Ophtalm. And Vis. Sci: 28 (7): 1164-1169, 1987) The composition proposed by us for food supplement, as a useful therapeutic aid in the prevention and treatment of cataracts and which forms the subject of the present invention, is the following:

For each composition capsule we named "OCUCLAR" (registered trademark).

Thanks to the balanced quantities of vitamins, amino acids and trace elements, this formulation allows to act along the already exposed metabolic pathway simultaneously on several fronts and in a sequential manner. In this way a considerably greater antioxidant effect is obtained than that expected both from the administration of each single component and from the simple additive effect.

Nicotinamide, which is the precursor of NADPH, avoids the problem of reduced shunt activity.

Riboflavin is the precursor of FAD, the coenzyme of glutathione reductase, an enzyme necessary to keep glutathione in its reduced form.

The three amino acids (cysteine, glycine, glutamic acid) are an essential part of our formulation, components of the tripeptide glutathione which, if administered as such, would be hydrolyzed during the digestive process.

In fact, glutathione, contrary to many metabolites that are transported already preformed through the epithelium of the capsule, is synthesized "in loco", inside the lens, starting from its constituent amino acids (Rathbun WB, Glutathione Biosynthesis in the lens and erythrocite - " Red blood cells and lens metabol'sm "Ed. Srivastava SK - Elsevier / North Holland, New York: 168-1673, 1980).

The dosages indicated for the three amino acids are in fact balanced between them in order to reconstitute "in vivo" a corresponding quantity of glutathione.

Selenium, a coenzyme of glutathione peroxidase, participates as such in the hydrogen peroxide reduction process (Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG. Selenium: biochemical roles as a component of giutathion peroxidase. Science 179: 585-590, 1973).

The exogenous administration of ascorbic acid allows to obtain high concentrations of this vitamin in the aqueous humor. Vitamin A (in the form of beta-carotene) and vitamin E (dalfa-tocaferil acetate) also contribute to accentuating the antioxidant power of the composition thus formulated: in particular, vitamin E protects the membrane lipids from peroxidation.

An addition of sodium pyruvate in the composition is only optional. This endogenous molecule, with no possible toxic activity, can in fact contribute to the non-enzymatic reduction of hydrogen peroxide, with the formation of completely harmless metabolites.

The above composition, hereinafter referred to as "OCUCLAR" (registered trademark) differs both quantitatively and qualitatively from that of other dietary supplements present on the international market. The dosages we use are in fact remarkably low and in any case comply with the indications of the LARN (Recommended Daily Intake Levels of Energy and Nutrients for the Italian Population).

Therefore, the recommended intake of two capsules / day of "OCUCLAR" (registered trademark) by us does not present any risk of toxicity even if the food supplement is administered for long periods of time.

And this is essential for a product that is useful in preventing a slowly evolving pathology such as cataracts. Qualitatively, the simultaneous presence in "OCUCLAR" (registered trademark) of all the substances useful and necessary to carry out a sequential action of the single components along the same metabolic path, undoubtedly strengthens the preventive antioxidant effect.

Claims (6)

CLAIMS 1. Food composition that includes vitamins, trace elements and a mixture of L-glutamic acid, L-cysteine and gliein in balanced quantities in such a way as to reconstitute the L-glutathione tripeptide "in vivo". 2. Composition according to claim 1, wherein vitamin A (in the form of beta-carotene) and vitamin E (in the form of alpha-tocopheryl acetate) are used in the formulation in quantities ranging from 700 to 3500 I.U. and 3.35 to 6.71 mg respectively. 3. Composition according to claim 1, wherein the vitamins B2, C and PP are present in the formulation in quantities ranging from 0.6-30 mg, 30-100 mg and 5-30 mg respectively. 4. Composition according to claim 1, wherein the trace element present in the formulation is selenium in quantities ranging from 20 to 100 mg, coenzyme of glutathione oxidase which is part of the redox cycle of glutathione. 5. Composition according to claim 1, containing sodium pyruvate in pharmacologically acceptable quantities. 6. Use of the composition according to claim 1 as a therapeutic aid in the prevention of cataracts.