Composition in gel for oral administration

Abstract

The invention is related to a composition for oral administration comprising a mixture of water, glycerol, edible polymeric gums, citric acid, vitamin antioxidants, potassium sorbate which may further comprise at least an agent, whether therapeutic or nutritive, for its controlled-release into the human body. The composition according to the invention, formulated in gel form., is capable of dispersing, stabilising, and conveying said at least therapeutic or nutritive agent through the digestive tract, protecting it from oxidative and mechanical stress during digestion, regulating its release according to the pH of the surrounding environment, and thus ensuring them to reach the more distal tract of the intestine.

Description

[0001] “Composition in gel for oral administration”

[0002] Description

[0003] Field of the invention

[0004] The present invention concerns a gel composition comprising active molecules and supplements, formulated for oral administration.

[0005] Prior art

[0006] The development of systems for the safe administration of therapeutic agents and supplements, enabling effective absorption of active ingredients, plays a crucial role today. Due to improper or inadequate diets or as a result of eating disorders or diseases, deficiencies in a broad class of natural biological molecules essential for proper human body functioning (e.g., vitamins, amino acids, salts) may occur. This underscores the strategic role these agents play and the necessity of designing innovative and alternative methods and vehicles to deliver such molecules into the body to maximize bioavailability.

[0007] Among the numerous formulations available on the market for releasing therapeutic molecules and supplements, a significant portion has been designed for oral administration. This method generally facilitates patient compliance due to its simplicity and natural execution, increasing the likelihood of continuation and completion compared to more inconvenient, uncomfortable, and sometimes invasive methods, such as intravenous, inhalation, and subcutaneous routes.

[0008] These formulations, due to their diverse chemi cal -physical and structural characteristics, come in many forms in terms of appearance, shape, and composition, offering access to a wide range of delivery methods, including tablets, syrups, capsules, emulsions, dispersions, and solutions. Many of the formulations above mentioned are aqueous, dissolving and / or dispersing various components, including stabilizers, sweeteners, acidifiers, preservatives, antioxidants, and thickeners. These constituents are designed to contain, preserve, and release supplements or therapeutic molecules, such as active pharmaceutical ingredients. For example, US 2021 / 369674 Al describes a nutraceutical composition in gel or gummy material form for oral use capable of encapsulating an active compound, employing gelling / thickening agents like gum arabic, guar gum, and xanthan gum in amounts ranging from 0.1-7%. The document also includes the use of antioxidants, pH regulators, sweeteners, preservatives, and optionally water.

[0009] EA 026 289 Bl relates to a biologically active food additive in colloidal form for oral use, applicable in medicine and the food industry. The colloidal composition includes a biologically active ingredient (e.g., carotenes and vitamins) and a liquid carrier comprising a structuring agent (such as xanthan, guar gum, or acacia gum in an amount ranging from 0.005%-0.5%), pH regulators (e.g., citric acid), preservatives (e.g., potassium sorbate), and flavorings to mask taste and improve oral and gastrointestinal availability of active substances. US 2018 / 055777 Al focuses on the development of colloidal systems for delivering bioactive agents (nutrients, micronutrients, nutraceuticals, and drugs) in the dietary supplement and pharmaceutical industries. It specifically proposes a gel-forming composition comprising xanthan gum, an external matrix of water or oil among other ingredients, and a bioactive agent chosen from a nutraceutical, prebiotic, probiotic, or a combination thereof.

[0010] The document also requires that this composition includes acceptable pharmaceutically excipients such as diluents, preservatives, solubilisers, emulsifiers and adjuvants.

[0011] However, a significant limitation of oral administration lies in the harsh physiological environment that therapeutic or nutritional agents encounter during passage through the digestive tract. Before absorption by the gastrointestinal epithelium, the administered agent can undergo partial or complete degradation, primarily chemical, due to the pronounced acidity from gastric juice secretion in the stomach. Additionally, this degradation is exacerbated by the stomach's peristaltic movements, which not only push food through the digestive tube but also knead and grind it, exposing it to further degradation. This demonstrates that the bioavailability of the administered agent may be compromised by exposure to such aggressive conditions. The invention seeks to provide alternative compositions and formulations to overcome the challenges of prior art.

[0012] If not specifically excluded in the detailed description below, what is described in this chapter is considered an integral part of the description.

[0013] Summary

[0014] The main scope of this invention is to describe a new formulation capable of overcoming the previously mentioned drawbacks and limitations, offering an alternative and improved solution for the oral administration of therapeutic agents and supplements.

[0015] In particular, the present invention aims to describe how the chemical-physical properties of a combination of edible polymeric components allow the protection of administered agents from chemical and mechanical stress, as well as to detail the preparation method for the formulation. These and additional scopes can be achieved through the preparation of a hydrogel comprising xanthan gum, acacia gum, hydroxypropyl methylcellulose (HPMC), guar gum, ascorbic acid, tocopherol, and lycopene, potassium sorbate, and citric acid, with improved flavor, palatability, and gastric tolerance. The hydrogel is capable of dispersing, stabilizing, and delivering therapeutic molecules of interest throughout the digestive tract (up to 20% active ingredients by weight). It protects such molecules from oxidative and mechanical stress during digestion, regulates their release based on the surrounding pH, and allows them to reach the distal tract of the intestine.

[0016] These and other scopes, advantages, and features of the present invention will be further specified in a detailed description of the following preferred embodiments.

[0017] Definitions

[0018] In this document, the terms "comprises", "includes", "has", "having", "bearing", "contains", "containing", "characterized by", or any variations thereof are intended to indicate a nonexclusive inclusion, subject to any explicitly stated limitations. For example, a composition, mixture, process, or method comprising a list of elements is not necessarily limited to those elements but may include other elements not explicitly listed or inherent to such composition, mixture, process, or method.

[0019] The term "agent" used in this patent includes therapeutic agents such as active pharmaceutical ingredients, as well as supplements and their components.

[0020] The term "supplements" or "nutrients" refers to products intended for dietary consumption to supplement the regular diet or serve as a concentrated or non-concentrated source of nutrients or other substances with a nutritional or physiological effect.

[0021] The term "therapeutic agent" or "active molecule" used in this patent refers in its broadest sense to a compound, substance, or entity with therapeutic or health-improving effects. Similarly, in this patent, the terms "nutrient" and "dietary supplement" are synonymous with "supplement" and do not restrict or limit the scope of the term.

[0022] Additionally, used synonyms for "therapeutic agent," such as "active ingredient," "active compound," or simply "active," must be understood as merely substituting and not restricting or limiting the scope of the expression itself.

[0023] All ranges describing percentage quantities of the components of the composition according to the invention are to be understood as percentages by weight.

[0024] The values defining the extremes of the above-mentioned ranges are to be understood as being included in the ranges.

[0025] Degrees Brix denoted °Bx is a measure of the amount of solid-state substances dissolved in a liquid and herein describes the amount of dissolved and / or dispersed solutes in the aqueous phase of the gel.

[0026] The abbreviation E.S. in this patent is an abbreviation of the term ‘dry extract’.

[0027] Description of the invention

[0028] The present patent relates to a new formulation to deliver and release supplements and / or therapeutic agents into the human body. The invention describes a novel combination of edible polymeric thickeners and other molecules, combined in indicted percentage-concentration ranges to form a matrix capable of preserving and releasing administered agents in an efficient and controlled manner, preventing degradation during passage through the digestive tract and increasing their bioavailability.

[0029] The composition of the invention includes water, vegetable glycerol, guar gum, acacia gum, hydroxypropyl methylcellulose (HPMC), xanthan gum, tocopherol, ascorbic acid, lycopene, potassium sorbate, and citric acid. This combination of elements results in a formulation, preferably in a gel form, with improved flavor, palatability, and gastric tolerance, capable of dispersing, stabilizing, and delivering therapeutic molecules of interest through the digestive tract (up to 20% active ingredients by weight), that protects these molecules from oxidative and mechanical stress during digestion, regulates their release based on the pH of the surrounding environment, and allows them to reach the distal part of the intestine.

[0030] The composition of the invention is provided in the form of a gel / polymeric matrix / hydrogel.

[0031] The composition includes the following components in specific weight percentages:

[0032] - Water: 40%-66%,

[0033] Vegetable glycerol: 5%— 12%,

[0034] Guar gum: 0.05%-0.25%,

[0035] Acaci a gum : 0.50%- 1.50%,

[0036] Hydroxypropyl methylcellulose (HPMC): 0.025%-0.15%,

[0037] Xanthan gum : 0.50%- 1.50%,

[0038] Tocopherol: 0.0001%-0.001%,

[0039] Ascorbic acid: 0.0001%-0.001%,

[0040] Lycopene: 0.003%-0.01%,

[0041] - Potassium sorbate: 0.10%-0.50%,

[0042] Citric acid: 0.50%-3.50%.

[0043] The composition according to the present invention may optionally include at least one therapeutic agent and / or supplement.

[0044] In a preferred embodiment, the composition according to the invention further comprises one or more agents selected from therapeutic agents, nutrients, supplements, or other ingredients used in dietary supplements in an amount ranging from 0.00001% to 20%. The composition according to the present invention may also include at least one sweetener and / or preservative; by way of example and not limited to, preferred sweeteners are selected from the group comprising sucralose, stevia, erythritol, fructose, maltitol, isomaltitol, sorbitol, and xylitol.

[0045] In a preferred embodiment, the sweetener and / or preservative is present in an amount ranging from 0.00001% to 20% for each sweetener and / or preservative.

[0046] In a preferred embodiment, the composition includes at least one sweetener selected from the group consisting of fructose, erythritol, sucralose, and stevia.

[0047] In a preferred embodiment the composition includes fructose and / or erythritol in amounts ranging from 0.00001% to 20%, to be intended for the individual sweetener, sucralose and / or stevia in amounts ranging from 0.00001% to 0.2%, to be intended for the individual sweetener. The composition according to the present invention may optionally include at least one flavoring agent: by way of example and without limitation, flavoring agents selected from the group comprising natural grape flavor, red grape flavor, natural citrus flavor, lemon flavor, orange flavor, and natural cola flavor, are particularly preferred.

[0048] In a preferred embodiment, the flavoring agent is present in an amount ranging from 0.00001% to 1.00%, to be intended for the individual flavoring agent.

[0049] As described above, the composition according to the invention may include therapeutic agents and nutrients. By way of example and without limitation, such molecules may be selected in the group consisting of vitamins, minerals, amino acids, carbohydrates, plant extracts, prebiotics, probiotics, flavonoids, as free compounds or glycosylated forms, and other substances and nutrients with nutritional or physiological effects.

[0050] By way of example and without limitation, the composition may include Vitamin A, B- complex vitamins (e.g., Bl, B2, B3, B5, B6, B7, B9, B12), Vitamin C, Vitamin D, Vitamin E, and Vitamin K.

[0051] Vitamins according to the invention may be used in any chemical form known to the expert in the field.

[0052] A particularly preferred example is Vitamin B9 in the form of folic acid. By way of example and without limitation, the composition may further comprise at least one of calcium, phosphorus, magnesium, potassium, potassium citrate, sodium, sodium alginate, chlorine, iron, zinc, zinc gluconate, sodium hyaluronate, fluorine, iodine, selenium, sodium selenite, cobalt, tryptophan, tyrosine, valine, serine, cysteine, histidine, threonine, valine, alanine, methionine, acetyl-L-carnitine, L-arginine base, isomaltulose, naringin, naringenin, hesperetin, eriocitrin, eriodictyol, apigenin, luteolin, quercetin, rutin, kaempferol, resveratrol, [6]-gingerol, [8]-gingerol,

[0010] -gingerol,

[0012] -gingerol, [4]-shogaol, [6]-shogaol, [8]-shogaol,

[0010] -shogaol,

[0012] -shogaol, in neutral, salted, complexed or any other chemically acceptable form.

[0053] The composition according to the invention may also include maltodextrin in amounts ranging from 0.00001% to 35%.

[0054] By way of example and without limitation, the composition the may include as an agent at least one chosen from the group of extracts sage, liquorice, nettle, green tea, grape seed, turmeric, ginseng, ginseng (root), bilberry, oat, thistle, hawthorn, red ginseng (Panax ginseng C.A. Mey.) root e.g. E.S. titrated at 5% ginsenosides, tamarind (fruit) E.S, Malva sylvestris L. leaves e.g. E.S. titrated at 25% of polysaccharides (Malva E.S.), taurine, coenzyme Q10, Icelandic lichen E.S. (Cetraria Islandica Ach. Thallus), Emblica Officinale E.S. (Phyllanthus Emblica L.fructus) and mixtures thereof.

[0055] The composition may further comprise at least one of inulin, fructo-oligosaccharides (FOS), galacto-oligo-saccharides (TOS), gluco-oligo-saccharides (GOS) and soy-oligo-saccharides (SOS), (alpha-GOS, alpha-galacto-oligosaccharide), partially or fully hydrolysed guar gum fibres, preferably 100% enzymatically hydrolysed guar gum having a density between 0. 20 - 0.24 g / mL (e.g., SUNFIBER® AG ).

[0056] Among probiotics, by way of example without limitation, Lactobacillus acidophilus, Bifidobacterium bifidum, Lactobacillus rhamnosus, Lactobacillus plantarum, Bifidobacterium breve, Bifidobacterium longum, Lactobacillus casei, Lactobacillus Lactis, Lactobacillus Bulgaricus, Lactobacillus Salvarius, Lactobacillus Acidophilus HA122 tindalysed may also be included. The composition according to the invention allows for an improved gastric tolerance formulation capable of dispersing, stabilising and conveying agents of interest in the digestive tract.

[0057] For this reason, compositions achieving a pH range of 3.9 to 4.9 are particularly preferred.

[0058] In a preferred embodiment, the composition according to the invention achieves a sugar concentration between 30 °Bx and 55 °Bx.

[0059] In another preferred embodiment, the composition has a density ranging from 1.1 g / mL to 1.3 g / mL.

[0060] The composition according to the present invention achieves an improved bioavailability of at least one contained therapeutic agent or supplement compared to when the same active is supplied individually.

[0061] This improved bioavailability is achieved using an edible polymeric gel matrix consisting of guar gum, acacia gum, hydroxypropyl methylcellulose (HPMC), and xanthan gum. The matrix is capable of encapsulating and retaining therapeutic molecules, protecting them from chemical, oxidative, and mechanical stress in the stomach. The chemical composition of the mentioned polymeric thickeners is such that, under low pH conditions, it resists chemical degradation and maintains a compact structure, limiting swelling and the release of encapsulated molecules while isolating them from the surrounding environment.

[0062] Once the gastric attack has passed and the therapeutic agents and / or supplements contained within have been protected, the polymer matrix relaxes and conformationally opens at the gut level where the pH approaches neutrality. As it relaxes, the polymer matrix can swell with water favouring the release of active ingredients and nutrients and their absorption in the intestine.

[0063] Not only that, the cross-linked structure conferred by the edible polymer composition allows better dispersion and separation of the antioxidants contained within. In fact, the matrix of thickening agents, by preventing aggregation of the molecules and improving their solubility, allows the antioxidants to better perform their function of protecting the therapeutic molecules from oxidative stress during digestion. To further investigate the molecular interactions stabilizing the gel, a molecular dynamics (MD) simulation was performed.

[0064] First, all the main molecular constituents of the gel according to the invention were reconstructed and parametrised in a virtual environment. In particular:

[0065] • Structural components: all those polymers that contribute to the formation of the three- dimensional gel network that acts as a carrier for the active ingredients. More specifically, we have arabinogalactan, a polysaccharide of gum arabic consisting of a galactan skeleton with side chains formed by glucose and arabinose; GAGP, a hydroxyproline-rich arabinogalactic glycoprotein of gum arabic; galactomannan, the main constituent of guar gum and trisaccharide formed by mannose and galactose units; xanthan, a polysaccharide containing hexoses such as D-glucose and D- mannose, as well as D-glucuronic and pyruvic acids; hydroxypropyl methyl cellulose (HPMC), a derivative of cellulose that exhibits the formation of ether bonds with the introduction of hydroxypropyl groups.

[0066] • Antioxidants: ascorbic acid, powerful water-soluble antioxidant; tocopherol, powerful fat-soluble antioxidant; lycopene, acyclic isomer hydrocarbon of beta-carotene belonging to the carotenoid group.

[0067] As described in figure 1, all the above-mentioned components were placed in a cubic simulation space with periodic conditions at the edges. The remaining three-dimensional space was filled with water molecules and chlorine / potassium ions in order to achieve system neutrality.

[0068] The system was simulated following a standard minimisation, equilibration and production phase protocol. Isotropic conditions were applied as per literature [1] for the simulation of systems in solution.

[0069] Upon analysis of the resulting structure after the 20 ns (sufficient time to allow the phases to mix and the system to reach equilibrium) of simulation, it immediately becomes clear how the structural components in Figure 2 allow for a dispersed organisation of the antioxidants, especially the lipophilic ones (lycopene and tocopherol) which would tend to aggregate in aqueous solution.

[0070] Indeed, as can be seen from Figures 3 and 4, lycopene and tocopherol entertain apolar interactions by virtue of their hydrophobic character without forming macro-aggregates and thus maintaining a good degree of solubilisation in the gel. The just-described interactions lead to the formation of:

[0071] • Tocopherol-lycopene dispersed pairs in a 1 : 1 ratio as shown in Figure 3

[0072] • Tocopherol-ascorbic acid-lycopene dispersed triplets in a 1 :1 ratio as shown in Figure 4

[0073] The stable interactions between the three antioxidants are able to assist the regeneration mechanisms, without impairing the antioxidant activity itself, which is guaranteed by a good solubilisation of the components in the gel.

[0074] Not only that, as shown in Figure 5, the specific coordination between the hydroxypropyl methylcellulose (HPMC) polymers and the lycopene molecules demonstrates that HPMC is an excellent suspending agent for lycopene.

[0075] The stability of the complex is mainly due to the hydrophobic interaction between the hydroxypropyl groups of the HPMC and lycopene. (Figure 6)

[0076] From analysis of the data, we can state that:

[0077] • The structural components of the gel interact well to form a dense three-dimensional network that can best disperse the antioxidant components, even those with a predominantly hydrophobic character that would then tend to agglomerate and precipitate.

[0078] • The fat-soluble antioxidants (lycopene and tocopherol), although dispersed, maintain specific interactions, joining in dispersed pairs. A spatial proximity is important to facilitate electronic exchanges during post-radical scavenging regeneration.

[0079] • In addition to fat-soluble pairs, triplets (lycopene, tocopherol and ascorbic acid) maintain stable interactions. Here again, spatial proximity aids the synergy of the three molecular species in radical scavenging. Hydroxypropylmethylcellulose (HPMC) proves to be an excellent suspending agent for lycopene, as stable and specific interactions between lycopene and HPMC are clearly evident from the simulation.

[0080] Examples

[0081] Preparation of the Composition

[0082] The general method of preparing the composition according to the present invention is described below. The composition according to the present invention may be obtained by the method described below or by slight modifications of this method which are in any case within the reach of the person skilled in the art. Modifications of the method may include, inter alia, the order of events described, timing, rotation speeds of the homogeniser or mixer and other conditions known to those skilled in the art.

[0083] The preferred steps for preparing the gel composition according to the present invention are as follows:

[0084] • Weigh the water

[0085] • Dissolve / disperse potassium sorbate, citric acid, sweeteners, preservatives, and active ingredients in the water

[0086] • Stir for 30 minutes at 500 rpm (using a mixer)

[0087] • Add Vitamin C, Vitamin E, lycopene, glycerol, and any optional flavorings.

[0088] • Stir for another 30 minutes at 500 rpm (using a mixer)

[0089] • Check pH and Degrees Brix, and if necessary, adjust the values using citric acid or sweeteners to bring them within the reference range

[0090] • Add the gelling agents one at a time under stirring at 250 rpm (using a mixer), ensuring complete homogenization of each before proceeding to the next, in the following order:

[0091] I. Acacia gum

[0092] II. Guar gum

[0093] III. Hydroxypropyl methylcellulose

[0094] IV. Xanthan gum • Mix for 15 minutes using a homogenizer set to 18,000 rpm.

[0095] Materials and Methods

[0096] To carry out the present invention and achieve the embodiments within the claimed scope, standard laboratory glassware (e.g., beakers of various capacities), a homogenizer (maximum 30,000 rpm, 500 W), or similar equipment and a propeller stirrer or equivalent are required. An expert in the field will have no difficulty identifying comparable tools to execute the invention.

[0097] Example Compositions

[0098] Several preferred examples of compositions according to the present invention have been prepared, and the pH and degrees Brix were measured for each composition. The compositions are described as follows:

[0099] Product 1: water 47.564%, maltodextrin 29.759%, vegetable glycerol 5.945%, citric acid 3.329%, xanthan gum 0.793%, acacia gum 0.793%, guar gum 0.063%, hydroxypropyl methylcellulose 0.040%, potassium sorbate 0.190%, lycopene 0.007%, ascorbic acid 0.0002%, tocopherol 0.0002%, sodium selenite 0.0005%, L- base Arginine 5.945%, taurine 1.982%, acetyl-L-camitine 1.982%, ginseng (root) 0.793%, coenzyme Q10 0.079%, zinc gluconate 0.457%, vitamin B3 0.063%, vitamin B5 0.024%, vitamin B2 0.0055%, vitamin B6 0.0055%, vitamin Bl 0.0044%, vitamin B9 0.0008%, vitamin B12 0.00001%, natural cola flavouring 0.159%.

[0100] Measured characteristics:

[0101] - Degrees Brix 53.2 °Bx,

[0102] - pH 4.5.

[0103] Product 2: water 52.2%, erythritol 16.71%, vegetable glycerol 8.70%, citric acid 0.61%, xanthan gum 0.87%, acacia gum 0.87%, guar gum 0.07%, hydroxypropylmethylcellulose 0.044%, potassium sorbate 0.21%, lycopene 0.0073%, ascorbic acid 0.0002%, tocopherol 0.0002%, 100% enzymatically hydrolysed guar gum with a density of 0.20 - 0.24 g / mL (e.g, SUNFIBER® AG) 5.80%, alpha GOS 5.80%, tamarind (fruit) E.S. 5.80%, mallow E.S. 2.03%, red grape flavour 0.22%. Measured characteristics:

[0104] - Degrees Brix 37.5 °Bx,

[0105] - pH 4.6.

[0106] Product 3: water 61.371%, erythritol 16.078%, vegetable glycerol 10.805%, citric acid 0.51%, xanthan gum 0.864%, acacia gum 0.864%, guar gum 0.069%, hydroxypropylmethylcellulose 0.086%, potassium sorbate 0.207%, lycopene 0.0073%, ascorbic acid 0.0002%, tocopherol 0.0002%, stevia 0.017%, alpha GOS 8.644%, lactobacillus acidophilus 0.519%, lemon flavouring 0.242%.

[0107] Measured characteristics:

[0108] - Degrees Brix 32.2 °Bx,

[0109] - pH 4.15.

[0110] Product 4: water 65.81%, erythritol 17.23%, vegetable glycerol 8.97%, citric acid 0.63%, xanthan gum 0.897%, acacia gum 0.897%, guar gum 0.090%, hydroxypropylmethylcellulose 0.045%, potassium sorbate 0.22%, lycopene 0.0075%, ascorbic acid 0.0002%, tocopherol 0.0002%, sodium alginate 2.244%, potassium citrate 1.795%, sodium hyaluronate 0.449%, Icelandic lichen E.S. 0.269%, emblica E.S. 0.224%, orange flavouring 0.22%.

[0111] Measured characteristics:

[0112] - Degrees Brix 36.1 °Bx,

[0113] - pH 4.8.

[0114] Example inhibition of protein denaturation

[0115] For the protein denaturation inhibition test, the following composition was used: water 66%, glycerol 12%, guar gum 0.20%, acacia gum 1.40%, HPMC 0.13%, xanthan gum 1.40%, Vitamin E 0.001%, Vitamin C 0.001%, lycopene 0.003%, potassium sorbate 0.5%, citric acid 0.5%, BSA (Bovine Serum Albumin) 17.9%.

[0116] The protein denaturation inhibition assay was performed by adapting widely standardized protocols [2], BSA was dissolved in water at a 10% concentration until a homogeneous solution was obtained. The gel composition according to the invention was then added. The mixture was diluted 1 : 1 with simulated gastric fluid [3], consisting of ultrapure water and IM HC1 (10%), so that the final pH was 1.8. After 2 hours of stirring (600 rpm) at 37°C, the sample was cooled to room temperature, and the solution’s turbidity was measured at 660 nm. Each measurement was performed in triplicate.

[0117] The positive denaturation control (CTRL) was prepared by introducing the gel composition components after a preliminary treatment of the BSA for 2 hours with water and HC1 at pH 1.8.

[0118] For both the sample and the positive denaturation control, two blanks (without the addition of BSA) were prepared following the same operational procedures. This allowed confirmation that the observed turbidity was attributable exclusively to the BSA and not to the gel components.

[0119] The inhibition of protein denaturation in the tested sample was compared with the positive denaturation control using the following formula: 100

[0120] Results and Considerations

[0121] The average absorbance of the sample is statistically lower (p*** < 0.001) than the average absorbance of the CTRL (Figure 7).

[0122] Based on the calculation using the formula above, the inhibition of protein denaturation in the presence of the composition is 76.5% compared to the positive control. 100 = 76, 5

[0123] BSA undergoes degradation and hydrolysis at pH = 2 [4], At this pH value, the protein tends to destabilize, causing aggregation and precipitation, with a consequent increase in the medium's turbidity. The data obtained from this experiment indicate that the components of the gel composition preserved BSA from denaturation during the simulated gastric phase, confirming the protective action of the gel observed in in silico tests.

[0124] It can be concluded that the gel composition of the present invention represents an effective vehicle for delivering substances through the gastrointestinal tract, protecting the molecules of interest from the acidic and mechanical stress of digestion. Its use in dietary supplement formulations is particularly innovative, as it offers advanced protection for active substances, promoting their controlled and targeted release. This approach improves the bioavailability of active ingredients, reducing losses during passage through the highly acidic stomach environment and subsequent transit through the intestine, where absorption occurs. Its stabilizing and gradual release properties make it ideal for therapeutic applications, optimizing treatment efficacy.

[0125] References

[0126] [1] The computational investigation of thermal conductivity of 1 IS globulin protein for biological applications: Molecular dynamics simulation Yu Fang et al. Journal of Molecular Liquids Volume 346, 15 January 2022, 118267.

[0127] [2] Sangeetha et al., 2016.

[0128] [3] Brodkorb et al., 2019.

[0129] [4] Estey et al., 2006.

[0130] Brief Description of Figures

[0131] - Figure 1: Simulation cube showing structural components (visualized as sticks) and antioxidants (visualized as balls), while water and salts are hidden for clarity.

[0132] - Figure 2: Antioxidants (in balls) dispersed in the gel’s 3D structure (in sticks). Water molecules and salts are hidden for clarity.

[0133] - Figure 3: Lycopene and vitamin E pairs (both in balls).

[0134] - Figure 4: Lycopene, vitamin E, and vitamin C triplets (all in balls). - Figure 5: Interaction between lycopene molecules and HPMC (both in balls).

[0135] - Figure 6: Lycopene molecule (in balls) and HPMC molecule (in sticks) with all atoms explicitly shown.

[0136] - Figure 7: Statistical analysis (t-test, p***) of absorbance differences between the positive denaturation control (gray) and the sample (yellow) at 660 nm.

Claims

Claims1. A composition for oral use comprising:- water in an amount between 40% and 66%,- vegetable glycerol in an amount of between 5% and 12%,- Guar gum in an amount of between 0.05% and 0.25%,- acacia gum in an amount between 0.50% and 1.50%,- hydroxypropyl methyl cellulose in an amount between 0.025% and 0.15%,- xanthan in an amount between 0.50% and 1.50%,- tocopherol in an amount between 0.0001% and 0.001%,- ascorbic acid between 0.0001% and 0.001%,- lycopene in quantities between 0.003% and 0.01%,- potassium sorbate in an amount of between 0.10% and 0.50%,- citric acid in an amount between 0.50% and 3.50%.

2. Composition according to the preceding claim further comprising one or more therapeutic and / or nutritional agent(s) in an amount of from 0.00001% to 20% preferably chosen from the group consisting of vitamins, minerals, amino acids, carbohydrates, plant extracts, prebiotics, probiotics, flavonoids, as such or in glycosylated forms, other substances and nutrients having a nutritional or physiological effect.

3. Composition according to any one of the preceding claims further comprising at least one preservative or sweetening agent, in an amount preferably between 0.00001% and 20% per individual sweetener or preservative.

4. Composition according to any one of the preceding claims further comprising at least one flavouring in an amount preferably between 0.00001% and 1.00%, per single flavouring.

5. Composition according to any one of the preceding claims wherein the composition is in gel form.

6. Composition according to any one of the preceding claims wherein the compositionhas a pH between 3.9 and 4.9.

7. Composition according to any one of the preceding claims wherein the composition has degrees Brix between 30 and 55 °Bx.

8. Composition according to any of the preceding claims comprising:- water 65.81%,- vegetable glycerol 8.97%,- citric acid 0.63%,- xanthan gum 0.897%,- acacia gum 0.897%,- guar gum 0.090%,- hydroxypropyl methyl cellulose 0.045%,- potassium sorbate 0.22%,- lycopene 0.0075%,- ascorbic acid 0.0002%,- tocopherol 0.0002%, in which the composition further comprises:- erythritol 17.23%,- sodium alginate 2.244%,- potassium citrate 1.795%,- sodium hyaluronate 0.449%,- Icelandic lichen E.S. 0.269%,- emblica E.S. 0.224%,- orange flavouring 0.22%.

9. Composition according to any one of claims 1-7 comprising:- water 61.371%,- vegetable glycerol 10.805%,- citric acid 0.51%,- xanthan gum 0.864%,- acacia gum 0.864%,- guar gum 0.069%,- hydroxypropyl methyl cellulose 0.086%,- potassium sorbate 0.207%,- lycopene 0.0073%,- ascorbic acid 0.0002%,- tocopherol 0.0002%, in which the composition further comprises:- erythritol 16.078%,- stevia 0.017%,- alpha GOS 8.644%,- lactobacillus acidophilus 0.519%,- lemon flavouring 0.242%.

10. Composition according to any one of claims 1-7 comprising:- water 47.564%,- vegetable glycerol 5.945%,- citric acid 3.329%,- xanthan gum 0.793%,- acacia gum 0.793%,- guar gum 0.063%,- hydroxypropyl methyl cellulose 0.040%,- potassium sorbate 0.190%,- lycopene 0.007%,- ascorbic acid 0.0002%,- tocopherol 0.0002%, in which the composition further comprises sodium selenite 0.0005%, maltodextrin 29.759%, L-Arginine base 5.945%, taurine 1.982%, acetyl-L-carnitine 1.982%, ginseng (root) 0.793%, coenzyme Q10 0.079%, zinc gluconate 0.457%, vitamin B30.063%, vitamin B5 0.024%, vitamin B2 0.0055%, vitamin B6 0.0055%, vitamin Bl 0.0044%, vitamin B9 0.0008%, vitamin B12 0.00001%, natural cola flavouring 0.159%.

11. Composition according to any one of claims 1-7 comprising:- water 52.2%,- vegetable glycerol 8.70%,- citric acid 0.61%,- xanthan gum 0.87%,- acacia gum 0.87%,- guar gum 0.07%,- hydroxypropyl methyl cellulose 0.044%,- potassium sorbate 0.21%,- lycopene 0.0073%,- ascorbic acid 0.0002%,- tocopherol 0.0002%, in which the composition further comprises:- erythritol 16.71%,- 100% enzymatically hydrolysed guar gum and having a density between 0.20 - 0.24 g / mL 5.80%,- alpha GOS 5.80%,- Tamarind (fruit) E.S. 5.80%,- Mallow E.S. 2.03%,- Red grape aroma 0.22%.

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