Antioxidant formulation for oral food supplement

Abstract

Disclosed is an antioxidant formulation having enhanced absorption and antioxidant activity to address the challenges encountered in utilizing antioxidant oral food supplements. Said antioxidant formulation comprising S-acetylglutathione (SAG), superoxide dismutase (SOD), and maltodextrin. Preferably, an antioxidant formulation as an oral food supplement comprising 100 - 1000 mg SAG, 50 - 300 IU SOD, and 10 - 100 mg maltodextrin.

Description

ANTIOXIDANT FORMULATION FOR ORAL FOOD SUPPLEMENTFIELD OF UTILITY MODEL

[0001] This utility model relates to an effective antioxidant formulation for oral food supplement. More particularly, it relates to an antioxidant formulation comprising of S-acetyl glutathione (SAG), superoxide dismutase (SOD) and maltodextrin.DESCRIPTION OF THE UTILITY MODEL

[0002] Oxidative stress is an alteration in the balance between reactive oxygen species (ROS) generation and antioxidant buffering capacity causing alterations in the cellular metabolism and its regulation and damaging cellular constituents. Oxidative stress plays a central role in the sustained immuno-inflammatory responses that accompany various ailments (Ribeiro, 2023).

[0003] ROS are produced during metabolic and immune system function, where molecular oxygen (O2) can unpair and leave free radicals which are highly unstable and reactive, leading to the formation of ROS. This makes them highly unstable and reactive with other molecules to produce more stable species. The mitochondria (electron transport of the respiratory chain) produce over 90% of cellular ROS, but inflammation and transition metal ions are involved. The metabolism of drugs and xenobiotics, cigarette smoke and environmental pollutants and radiation, known as avoidable sources, can cause imbalance on the redox state (Ribeiro, 2023).

[0004] The enzyme systems that produce ROS are cytochrome P450, the mitochondrial respiratory chain, xanthine oxidase, uncoupled endothelial nitric oxide synthase, heme oxygenase, myeloperoxidase, lipoxygenase, cyclooxygenase, and nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidases (Ribeiro, 2023).

[0005] When a cell is not stressed, the processes that generate ROS are well counterbalanced by antioxidant systems. Since ROS are constantly generated during normal cellular metabolism, this means that if there is a change on the balance of prooxidant / antioxidant system in favour of prooxidant there will be damage to the cellular macromolecules. If cells are not capable of coping with the intensity of oxidative stress, this can cause lipid, protein and DNA damage that culminate in death via necrosis or apoptosis. That can happen under pathological conditions where ROS generation may be sharply increased, overwhelming the capacity of the cellular antioxidant defense system (Ribeiro, 2023).

[0006] The human body includes endogenous mechanisms that may function as antioxidants (local and systemically), and they can be complemented by the provision of exogenous antioxidants carried in by the diet or as a supplement. The consumption of the exogenous antioxidants are very useful, since they can maintain or re-establish the redox homeostasis, either inhibiting the ROS production or indirectly by the enhancement of endogenous antioxidant systems, providing a prophylactic and therapeutic tool against many diseases (Riberio, 2023).

[0007] Glutathione, also referred to as GSH, is an endogenous component of cellular metabolism, a tripeptide composed of glycine, cysteine, and glutamic acid (Gad, 2024). It is the most abundant low-molecular weight thiol-containing metabolite in the majority of organisms (Ferreiraet al., 2023). GSH is often referred to as "the master antioxidant" and it is important for the protection of the cells from oxidative damage and maintaining redox homeostasis. GSH is often considered to be a key player of the defense system the first line of defense against oxidative damage. It is reported as a key player of the defense system. Enhanced ROS levels may require not only enhanced GSH action to maintain redox status, but also enhanced energy and material consumption to replace consumed GSH (Ribeiro, 2023).

[0008] It is carrier of an active thiol group (cysteine residue), it acts as an antioxidant, either directly by interacting with ROS and electrophiles, or by operating as a cofactor for various enzymes. The GSH is a cosubstrate of glutathione peroxidase (GPx) for the reduction of the hydrogen peroxide (H2O2) and of organic peroxides (LOOH - lipid peroxides) (Ribeiro, 2023).

[0009] The function on the elimination of reactive oxygen and nitrogen species is of great importance. GSH may either directly bind some ROS species or serve as a source of reductive power for certain antioxidant systems. GSH is an important antioxidant and reacts directly with ROS, RNS (NO•), and other reactive species, particularly HO•, HOCl, RO•, RO2•, O2, and ONOO−, and it is also involved on the detoxification of products derived from the oxidation of lipids (malonic dialdehyde and 4-hydroxy-2-nonenal) (Ribeiro, 2023).

[0010] Although GSH can directly bind to some ROS species, GSH cannot control the early stages of ROS cascade production. Instead, GSH can only fight secondary radicals. Further, chronic oxidative stress reduces the cell levels of GSH, and it is often appropriate to replenish its levels. Increasing GSH plasma levels may have beneficial systemic effects and may be of therapeutic relevance. GSH intake via the oral route does not successfully enhance GSH in plasma, due to its metabolism in the gut where it is hydrolyzed into its three constituent amino acids by a γ-glutamyl transpeptidase (γ-GT) present in the intestine. It is therefore necessary to use a high oral dose in order to guarantee significant absorption (Fanelliet al., 2018).

[0011] This utility model has been developed to address the foregoing issues by combining in a formulation S-acetyl glutathione, superoxide dismutase and maltodextrin. Specifically, said formulation enhances endogenous antioxidant system against increase in ROS generation. More specifically, the combination of S-acetyl glutathione, superoxide dismutase and maltodextrin, enhances the endogenous antioxidant system against secondary radicals and even early stages of ROS cascade production.

[0012] S-acetyl glutathione (SAG) is a GSH precursor, it is more stable than GSH itself in plasma and is taken up directly by cells and later converted to GSH. The acetylation of the sulfur atom prevents the decomposition of GSH and facilitates its absorption through the intestinal wall as is, thus enabling the molecule to pass extensively into the cells. Moreover, cysteinyl acetylation prevents the oxidation of the thiol group before its absorption. After absorption, SAG is hydrolyzed by cytoplasmic thioesterases, so releasing a GSH pool available for the cells. The addition of SAG to cultures of fibroblasts originating from individuals suffering from a genetic glutathione synthetase deficiency has proved able to replenish the intracellular level of GSH effectively. SAG has proven to be more stable in plasma and more effective than GSH in replenishing the cell levels of GSH depleted by viral infections (Fanelliet al., 2018).

[0013] Superoxide dismutases (SODs) are metalloenzymes that play a major role in antioxidant defense against oxidative stress in the body (Rosaet al., 2021). SOD can control ROS at the early stages, converting very dangerous and reactive superoxide anions (O2•−) into hydrogen peroxide (H2O2) through dismutation reaction. Catalase (CAT) and Glutathione Peroxidase (GPx) can then operate, eliminating the H2O2produced by the dismutation reaction of SOD, and thus preventing the production of hydroxyl radicals (OH•), harmful ROS able to damage biomolecules (BIONOV, 2016). SOD supplementation may therefore trigger the endogenous antioxidant machinery for the neutralization of free-radical excess and be used in a variety of pathological settings (Rosaet al., 2021).

[0014] GPx needs adequate GSH to neutralize H2O2, GSH fights secondary free radicals of other harmful ROS, and SOD can be reused to neutralize multiple free radicals while not being quickly exhausted. SOD and glutathione therefore works synergistically together in protecting the body from oxidative stress.

[0015] Maltodextrin is a nonsweet, nutritive saccharide polymer, with a dextrose equivalent (DE) of < 20. Starches from botanical sources like corn, potato, wheat, rice, tapioca, sago palm, barley, and sorghum can be used as raw material. Maltodextrins are used as a fat replacer (FR) in dairy products, confectionary, frozen desserts, cereal baked goods, and meat products due to their ability to form soft, spreadable, thermoreversible gels with melt-in-the-mouth properties (Chavan, 2016). In a study conducted by Hasanah, Huswatun entitled "Effect of Maltodextrin Concentration on Antioxidants Activity and Stability Wood (Caesalpinia Sappan L) in Various Conditions of PH and Temperature", antioxidant activity of natural dye powders of secang wood is observed to decrease with the increase in maltodextrin concentration. Said decrease is caused by the increasing number of fillers (maltodextrin), which will increase the total number of ingredients that do not contain antioxidants so that the percentage of total antioxidants in the measured natural dye powder of sapwood will be lower and the measured antioxidants will be less. On the other hand, in the study of Posridee, Kakanang entitled "Maltodextrin from Sweet Cassava: A Promising Endurance Enhancer", both maltodextrin and crude extract forms significantly boosted the activity of SOD.SUMMARY OF THE UTILITY MODEL

[0016] The primary object of the present utility model is to provide an antioxidant formulation having enhanced absorption and antioxidant activity. Said formulation comprises of SAG, SOD and maltodextrin.

[0017] Another objective of the present utility model is to produce the antioxidant formulation as an oral food supplement.

[0018] Still, the objective of the present utility model is to address the challenges encountered in utilizing antioxidant oral food supplements. Specifically, the ability of glutathione to bind directly to some ROS species cannot control early stages of ROS cascade production and limited only to addressing secondary radicals. SOD alone on the other hand, controls ROS at early stages by converting the very dangerous and reactive superoxide anions into hydrogen peroxide through a dismutation reaction. The hydrogen peroxide can then be converted into harmless H2O and O2by antioxidants CAT and GPx which are endogenous in the body. On the other hand, SOD activity is significantly boosted by maltodextrin. Therefore, the combination of SOD, glutathione and maltodextrin in the present utility model works synergistically in protecting the body from oxidative stress.

[0019] These and other objects will become apparent upon reading the following detailed description.DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0020] The present utility model provides an antioxidant formulation comprising 100 - 1000 mg SAG, 50 - 300 IU SOD and 10 - 100 mg maltodextrin. The complementary and synergistic mechanism of action among these key active ingredients can neutralize more effectively a wide range of oxidant species in our body cells than each ingredient can.

[0021] The following examples are not intended to limit the scope of the present utility model, but merely to concretely exemplify the process to be used and the results to be expected when this utility model is employed.Example 1

[0022] The antioxidant oral food supplement comprising of the following:COMPONENTAMOUNTS-acetyl glutathione100 mgSuperoxide dismutase50 IUMaltodextrin10 mgExample 2

[0023] The antioxidant oral food supplement comprising of the following:COMPONENTAMOUNTS-acetyl glutathione500 mgSuperoxide dismutase150 IUMaltodextrin50 mgExample 3

[0024] The antioxidant oral food supplement comprising of the following:COMPONENTAMOUNTS-acetyl glutathione1000 mgSuperoxide dismutase300 IUMaltodextrin100 mg

[0025] The superoxide dismutase having activity of approximately 50 IU – 300IU is prepared and assayed using known standard procedures. From results of the assay, 5 mg – 30 mg of superoxide dismutase, in powder form, will yield an activity of 50 IU – 300 IU.Example 4

[0026] The antioxidant oral food supplement of Examples 1 to 3 was prepared by mixing the respective amounts of S-acetyl glutathione, superoxide dismutase and maltodextrin. The resulting mixtures were then directly compressed into tablets and then were loaded into the tablet reservoir blister packaging machine.

[0027] There are no particular restrictions on the method for producing the tablet, either direct compression or tableting by the indirect tableting method may be used, but the direct tableting method is more preferred. In the case of the direct compression tableting method, if necessary, excipients, disintegrants, binders, lubricants, and other additives, are added to the antioxidant formulation and mixed as uniformly as possible. Mixing methods of the antioxidant formulation, excipients, lubricants, binders, disintegrants, other additives, and the like are not particularly limited, but mixing with a mixer is preferred.Example 5

[0028] The antioxidant oral food supplement of Examples 1 to 3 was prepared by mixing the respective amounts of S-acetyl glutathione, superoxide dismutase and maltodextrin. The resulting mixtures were then encapsulated using a continuous motion capsule filling machine. The speed setting was determined and capsule used was a hard, clear gelatin capsule, size 00. The capsules were weighed for their fill-weights. In the next step, the capsules were fed into a cleaner after filling and then were loaded into the capsule reservoir blister packaging machine.

[0029] There are no particular restrictions on the method for producing the capsule but using a fully automated capsule filling machine is more preferred. If necessary, excipients, disintegrants, binders, lubricants, and other additives, are added to the antioxidant formulation and mixed as uniformly as possible. Mixing methods of the antioxidant formulation, excipients, lubricants, binders, disintegrants, other additives, and the like are not particularly limited, but mixing with a mixer is preferred.

[0030] In addition to the above examples, the antioxidant oral food supplement may also take the form of granules, candies (i.e.gummies), drinks (i.e.instant coffee) and energy bars.

[0031] The present utility model is not to be limited in scope by the specific embodiments described herein. Indeed, various modifications of the utility model in addition to those described herein will become apparent to those skilled in the art from the foregoing description. Such modifications are intended to fall within the scope of the appended claims.

[0032] Various publications are cited herein, the disclosures of which are incorporated by reference in their entirety.

[0033] 1. Ribeiro, B.Glutathione: the master antioxidant. Ozone Therapy Global Journal. 2023. Volume 13, pp 175 - 197.

[0034] 2. Gad, S.Glutathione. Encyclopedia of Toxicology (Fourth Edition). 2024. Volume 4, pp 1001 - 1002.

[0035] 3. Ferreira, M.et al.Glutathione and peroxisome redox homeostasis. Redox Biology. November 2023. Volume 67, 102917.

[0036] 4. Fanelli, S.et al.Oral Administration of S-acetyl-glutathione: Impact on the Levels of Glutathione in Plasma and in Erythrocytes of Healthy Volunteers. International Journal of Clinical Nutrition & Dietetics. 2018. Volume 4, 134.

[0037] 5. Rosa, A.et al.Superoxide Dismutase Administration: A Review of Proposed Human Uses. Molecules. 2021. Volume 28, 1844.

[0038] 6. Chavan, R.S.et al.Fat Replacer. Encyclopedia of Food and Health. 2016.

[0039] 7. BIONOV.Customer Technical Support: What are the differences between SOD and other antioxidant molecules such as Vit C or CoQ10?CTS-0114. 2016.

Claims

An antioxidant formulation comprising of S-acetylglutathione (SAG), superoxide dismutase (SOD), and maltodextrin.The antioxidant formulation according to claim 1, wherein the amount of SAG is 100 mg to 1000 mg.The antioxidant formulation according to claim 1, wherein the amount of SOD is 50 IU to 300 IU.The antioxidant formulation according to claim 1, wherein the amount of maltodextrin is 10 mg to 100 mg.The antioxidant formulation according to claim 1, wherein said formulation is in a form of an oral food supplement.The antioxidant formulation according to claim 5, wherein the oral food supplement is in a form selected from tablets, capsules, granules, candies, drinks or energy bars.