Ginger and gamma cyclodextrin composition

Abstract

A composition comprising a mixture of ginger extract and gamma cyclodextrins, in liquid or gel form for oral consumption, which enables rapid and efficient delivery of the active ingredients of ginger through the gastric tract, limiting their degradation and promoting their release in the intestine.

Description

[0001] Ginger and gamma cyclodextrin composition

[0002] Description

[0003] Technical Field

[0004] The present invention refers to a composition for oral administration of ginger extracts by inclusion of its active ingredients within y-cyclodextrins.

[0005] Prior art

[0006] Ginger is a food widely appreciated in culinary circles not only for the distinctive citrusy, sparkling aroma it releases, but also for the numerous beneficial properties exerted by its active ingredients.

[0007] The roots of ginger, specifically the rhizomes, act as a store and reservoir of elements that are essential to the life and survival of the plant, which is why the highest concentrations of biologically active molecules are contained in these terminal swellings of the stem.

[0008] As is also well known, the active molecules contained in ginger exert a plethora of activities conducive to the body's state of good health and regulate its proper functioning.

[0009] Suffice it to say that ginger is still used in traditional Chinese and Indian medicine as an antiinflammatory, precisely because of its ability to inhibit cyclooxygenases and prevent the synthesis of prostaglandins, which are mainly responsible for the inflammatory state. Overall, the active molecules contained in ginger rhizomes aid digestion, exhibit anti-emetic properties, prevent gastric ulceration, reduce phenomena associated with motion sickness such as dizziness and nausea during pregnancy, and suppress flatulence, they accentuate caloric consumption and promote slimming, soothe inflammation and joint pain, control blood sugar levels, reduce blood pressure, regulate cholesterol concentration, prevent cellular senescence and rejuvenate the skin.

[0010] Not only that, these compounds are also recognised as having antibacterial, antifungal and larvicidal properties.

[0011] While the unmistakable aroma is conferred by the volatile essential oils such as monoterpenoids (e.g. P-fellandrene, geraniol, citral) and sesquiterpenoids (e.g. a-zingiberene, P-bisabolene, zingiberol), the ‘pungent’ and ‘spicy’ flavour is conferred by the less volatile phytochemical component. The latter consists mainly of gingerols, shogaols, paradols and zingerones. Gingerols are a family of molecules of an aromatic nature, having an aldolic and a phenolic functionality, distinguishable by their alkyl chain length and predominantly present in fresh ginger. When dehydrated (as in dried ginger), the gingerols convert to shogaols, i.e. molecules with the same skeleton but with an enonic functionality instead of an aldolic one and with a markedly ‘pungent’ property. The shogaols, either by cooking or metabolic activity, can then generate zingerones and paradols respectively.

[0012] Although the molecules contained in ginger are encompassed in a particularly wide library of compounds, including micronutrients, vitamins, flavonoids, essential oils and terpenes (e.g. P- bisabolene, a-curcumene, zingiberene), gingerols and shogaols are distinguished by their distinct biological activity and intrinsic ability to impart most of the beneficial properties listed above.

[0013] The amounts of gingerols and shogaols contained within ginger are indeed dependent on the culinary treatments and processing that ginger rhizomes undergo, but originally also on the quality, origin of the ginger itself, ripeness and light exposure. Gingerols and shogaols are also considered to be two powerful and efficient antioxidants, capable therefore of acting as free radical scavengers, preventing dangerous and sometimes seriously cell-damaging oxidative mechanisms. Given these premises, one can deduce the importance that ginger can and should play in our daily diet, and one can see how important it is to supplement our daily diet with the molecules it contains.

[0014] In order to be assimilated, like any other nutrient, the active ingredients of ginger must, however, pass through the entire gastric tract, i.e. pass unharmed through the gastric environment in order to be absorbed into the final part of the intestinal lumen. The aggressive conditions in the stomach, although necessary for the digestion and hydrolysis of complex protein and carbohydrate macrostructures, are often the cause of partial if not total chemical degradation of these often labile and chemically sensitive molecules. Not only that, but a further competing factor that can drastically affect the reduction of nutritional intake is the residence time in the gastric environment, which is strictly dependent on the amount of food ingested and in the case of liquids, on the osmotic pressure of the liquid itself. In fact, fluids with high osmotic pressure will tend to draw water into the stomach, lengthening the digestion time and bringing chemi cal -oxi dative stress on acid-sensitive compounds. It follows that, in order to be able to provide the human organism with a proper supply of shogaols and gingerols, and thus to benefit from their organoleptic and nutritive properties, it is necessary to develop new systems that allow these active ingredients to be quickly and efficiently conveyed through the stomach.

[0015] The scientific article ‘Biomolecules. 2020 Feb 22;10(2):344. doi: 10.3390 / bioml0020344' describes, for example, a composition comprising inclusion complexes between y- cyclodextrin and the active ingredients of ginger, in particular 6-gingerol, 8-gingerol and 10- gingerol, for use in a food matrix such as yoghurt.

[0016] JP 2015 231979A, on the other hand, describes an aqueous composition comprising an extract of black ginger and a combination of at least two cyclodextrins, in particular y-cyclodextrin and maltosyl-cyclodextrin, wherein said combination is capable of bringing the ginger actives into solution by including them in their apolar cavities and preventing their precipitation.

[0017] Unless specifically excluded in the detailed description that follows, what is described in this chapter is to be regarded as part of the description.

[0018] Summary

[0019] The main purpose of the present invention is to describe a new composition based on ginger extract that can overcome the aforementioned drawbacks and limitations, that favours protection from the gastric environment and that ensures efficient release of the active ingredients contained in ginger in the intestine.

[0020] This purpose can be achieved by a composition comprising ginger extract and a particular family of cyclodextrins, the y-cyclodextrins, which by incorporating said active ingredients allows their protection and transport along the digestive tract.

[0021] It is a further object of the present invention to describe a composition based on ginger extract and y-cyclodextrins that by means of reduced osmotic pressure can rapidly transit in the stomach, limiting the oxidative action of gastric juices.

[0022] An additional object of the present invention is to describe a composition based on y- cyclodextrins and ginger extract, which is capable of improving the solubility of the active ingredients contained therein and the attenuation of the ‘pungent’ taste.

[0023] Brief description of figures Figure 1. Simulation cube at time 0. Water is shown as surface; inside, a random starting arrangement of y-cyclodextrins (doughnuts) and ginger compounds; ions are visible as scattered dots in the medium.

[0024] Figure 2. Interaction between [6]-gingerol and y-cyclodextrin.

[0025] Figure 3. Interaction between [6]-shogaol and y-cyclodextrin.

[0026] Figure 4. Interaction between [8]-gingerol and y-cyclodextrin.

[0027] Figure 5. Interaction between [8]-shogaol and y-cyclodextrin.

[0028] Figure 6. Interaction between

[0010] -gingerol and y-cyclodextrin.

[0029] Figure 7. Interaction between

[0010] -shogaol and y-cyclodextrin.

[0030] Figure 8A. System 1 at the beginning of the simulation (0 ns).

[0031] Figure 8B. The molecular aggregate of system 1 at the end of 50 ns of simulation. Gingerols and shogaols are represented as Van der Waals spheres. Water and ions have been hidden for clarity.

[0032] Figure 9A. System 2 at the start of the simulation (0 ns).

[0033] Figure 9B. The molecular aggregate of system 2 at the end of 50 ns of simulation. Gingerols and shogaols are represented as Van der Waals spheres. Gamma cyclodextrins appear as sticks. Water and ions have been hidden for clarity.

[0034] Figure 10A. System 3 at the beginning of the simulation (0 ns).

[0035] Figure 10B. First representation of the three-dimensional network of y-cyclodextrins in system 3 at the end of 50 ns of simulation. Gingerols and shogaols are represented as Van der Waals spheres. Gamma cyclodextrins appear as sticks. Water and ions have been hidden for clarity.

[0036] Figure 10C. Second representation of the three-dimensional network of y-cyclodextrins in system 3 at the end of the 50 ns simulation. Gingerols and shogaols are represented as Van der Waals spheres. Gamma cyclodextrins appear as sticks. Water and ions have been hidden for clarity.

[0037] Figure 11 (A-B). Two open inclusion complexes detected in system 3: a gingerol molecule (right) and shogaol (left) are included in a gamma-cyclodextrin molecule.

[0038] Figure 12 (A-B). Two closed inclusion complexes detected in system 3 : a gingerol molecule (right) and shogaol (left) are respectively included in two gamma-cyclodextrin molecules.

[0039] Figure 13. Time course of total polyphenol content in glyceric extracts subjected to thermal and oxidative stress.

[0040] Definitions

[0041] - In this document, the terms, ‘comprises, ‘includes’, ‘has’, ‘having’, ‘bearing’, ‘contains’, ‘containing’, ‘characterised by’ or any other variation of these terms, are intended to cover a non-exclusive inclusion, subject to any expressly stated limitations. For example, a composition, mixture, process or method comprising a list of elements is not necessarily limited only to those elements, but may include other elements not expressly listed or inherent in that composition, mixture, process or method.

[0042] - All ranges shown and descriptive of the percentage amounts of each constituent element of the composition according to the present invention are to be understood as percentages by mass.

[0043] The amount of each constituent element of the composition according to the present invention expressed as a percentage range is to be understood as including the values at the edges of the range. Thus, if a constituent is between 10% and 20%, the extremes of the range are included in the range.

[0044] - In the present document, the term ‘y-cyclodextrin’ or its plural literally refers to gamma- cyclodextrin or its plural, i.e., a cyclized, truncated cone-shaped oligosaccharide comprising 8 monomers of D-(+)glucopyranose joined together with a, 1-4 glucosidic bonds.

[0045] The abbreviation D.E. contained in this patent is an abbreviation for ‘dry extract’.

[0046] The abbreviation E.G. contained in this patent is an abbreviation for ‘glyceric extract’ .

[0047] - Herein, the terms ‘active ingredients’, ‘active compounds’, ‘active ingredients’ or sometimes ‘compounds’ refer similarly and indifferently to the families of shogaols and gingerols contained in ginger and its dry and glyceric extracts.

[0048] - According to the present invention, by gingerols is meant the family of aldols comprising [6]-gingerol, [8]-gingerol,

[0010] -gingerol,

[0012] -gingerol.

[0049] - According to the present invention, shogaols means the family of enones comprising [4]- shogaol, [6]-shogaol, [8]-shogaol,

[0010] -shogaol,

[0012] -shogaol.

[0050] The term ‘alkyl’ or ‘alkyl chain’ or ‘alkyl fragment’ or ‘lipid tail’ or ‘alkyl tail’ refers to a carbon chain longer than 3 units, linear or branched, which may have heteroatoms (e.g. oxygen ‘O’) and alkenyl or alkynyl unsaturations within it.

[0051] Detailed Description

[0052] The present invention relates to a novel composition comprising ginger extract and y- cyclodextrins, capable of conveying the active ingredients contained in ginger through the gastric tract, protecting them from oxidation and chemical degradation and promoting their release in the intestine.

[0053] The transport of shogaols and gingerols through the digestive tract is mediated by a family of cyclodextrins, i.e. y-cyclodextrins, which act in effect as shuttle systems. The y-cyclodextrins, by means of the truncated cone-shaped apolar cavity made up of 8 glucosidic units, act as carriers and take in the molecules of interest, transport them to the intestine and allow their absorption.

[0054] Shogaols and gingerols represent two rather large classes of molecules. Given the size of these compounds, the maximum diameter of approximately 0.95 nm attained by the truncated cone structure of y-cyclodextrins is sufficiently large to allow these active compounds to be incorporated. Within each class, the different structural characteristics of the compounds, especially at the alkyl chain level, modulate the conformation and geometry of inclusion in y- cyclodextrins.

[0055] Thus, the ability of y-cyclodextrins to retain the active ingredients of ginger is not only- dependent on the diameter of the oligosaccharide ring, but also on the conformation, size and spatial distribution of the atoms of the active compounds.

[0056] The advantages of these inclusion systems are manifold.

[0057] Firstly, cyclodextrins, through the formation of host-guest complexes, greatly increase the solubility of the lipophilic compounds of ginger, i.e. gingerols and shogaols, avoiding their aggregation into lipophilic insoluble agglomerates.

[0058] Then, as also pointed out in the art note, the marked acidity to which nutrients are subjected in the stomach may cause decomposition, alteration or hydrolysis of said active ingredients. Encapsulation of the latter within chemically stable oligosaccharide rings offers protection from the aggressive environment, lowering the contact surface with the gastric juice and minimising the likelihood of degradation. A further advantage is closely linked to the intrinsic nature of y-cyclodextrins. Indeed, for the same amount (by mass) of sweetener administered, a single unit of y-cyclodextrin incorporates 8 glucoside units. The result of this is that for the same mass of sugar excipient contained in the composition, the use of y-cyclodextrins drastically lowers the molarity of the administered solution.

[0059] This results in a lowering of the osmotic pressure of the composition, which at the gastric level, leads to a reduced water uptake and therefore a shorter residence time in the stomach. Shorter residence times in the stomach result in a reduced likelihood of observing degradation of shogaols and gingerols, and thus a higher dosage of active ingredients will be able to reach the intestinal epithelium.

[0060] Finally, as a further advantage, the encapsulation of the active ingredients of interest within the oligosaccharide rings prevents the taste buds from detecting and coming into contact with gingerols and shogaols, thus masking the perception of the ‘spicy’ and ‘pungent’ taste characteristic of ginger.

[0061] It was also experimentally observed that in order to increase the stability of the inclusion complex between y-cyclodextrin and active ingredient, it is required that the molar ratio between the y-cyclodextrins and active compounds present in the ginger is greater than 1.

[0062] In an embodiment the composition according to the invention comprises y-cyclodextrin and ginger extract in a solvent suitable for food use, preferably water. The weight ratio in the composition between the y-cyclodextrin and the ginger extract is in the range of 0.1-3, preferably 0.333.

[0063] It is therefore an object of the present invention to provide a composition comprising y- cyclodextrin and ginger extract in which the weight ratio between the tw?o is in the range 0.1- 3.

[0064] In a preferred embodiment, the composition according to the present invention further comprises at least one thickener, preferably xanthan and / or acacia gum.

[0065] The thickening agent, especially xanthan, is able to assist the suspension of any particles that are not perfectly dissolved and then promote their assimilation through an ‘encapsulation’ effect of the active ingredients in its gelling matrix.

[0066] The use of xanthan also increases the consistency of the product favouring, for example, its administration in drops.

[0067] In a preferred embodiment, the composition further comprises at least one of:

[0068] - preservatives; - pH modulators;

[0069] - natural extracts;

[0070] - vitamins;

[0071] - sweeteners and / or sugars.

[0072] Particular favourites are lactic acid, citric acid and sodium lactate.

[0073] Among the vitamins particularly preferred is vitamin B6.

[0074] In a preferred form of embodiment, the composition comprises water, fructose, ginger glyceric extract (E.G.), chamomile D.E., lactic acid, y-cyclodextrin, citric acid, sodium lactate, vitamin B6, xanthan and acacia gum.

[0075] In this preferred embodiment, the use of a solvent more lipophilic than water, such as glycerol, for the extraction of the active ingredients of ginger enables the concentration of active ingredients in the ginger E G. to be increased and the antioxidant activity' of the bioactive ginger compounds to be preserved. The presence of glycerol further increases the vi scosity of the final composition. Glycerol therefore acts as a rheological modifier, increasing the flow resistance between adjacent fluid layers and minimising mixing. The resulting technical effect is a surprising protection of the active ingredients contained within the composition, which are thus safeguarded from the digestive process. Further details on this can be found in the Examples section (Example 1 ) of this detailed description, where the polyphenol content of ginger glyceric extracts was analysed.

[0076] The results of the experiment show that glycerol plays a significant role in protecting the antioxidant activity of ginger phenolic compounds, even under oxidative and thermal stress conditions. As the concentration of glycerol increases, greater conservation of total polyphenols is observed, demonstrating how unexpectedly glycerol acts as a stabiliser for the bioactive properties of ginger. This protective effect is particularly evident when comparing the glyceric extracts with the glycerol-free control, where the polyphenol content is significantly reduced due to oxidation. The use of glycerol as an alternative and protective solvent is an effective strategy to preserve the functional properties of plant matrices during processing and storage.

[0077] In particular, the composition according to the present invention comprises:

[0078] - Water in an amount of between 30% and 60%

[0079] - Fructose in an amount of between 0.00001% and 40%

[0080] - E.G. ginger in an amount between 4% and 16% - y-cyclodextrin in an amount between 0.1% and 5%

[0081] - D.E. Chamomile in an amount between 0.00001% and 8%

[0082] - Lactic acid in an amount between 0. 1% and 1.5%

[0083] - Citric acid in an amount between 0.5% and 1.8%

[0084] - Sodium lactate in an amount between 0.5% and 1.8%

[0085] - Vitamin B6 in an amount between 0.00001% and 0.02%

[0086] - Xanthan in an amount between 0.00001% and 4%

[0087] - Acacia gum in an amount between 0.00001% and 0,05%,

[0088] Further, the composition according to the present invention may comprise dry extract (D.E.) of ginger in an amount between 0.00001% and 1%.

[0089] Preferably, the composition according to the present invention is administered orally.

[0090] Preferably, the composition according to the present invention is formulated in liquid or gel form.

[0091] Preferably, the composition according to the present invention possesses a pH between 3.2 and 4.9, preferably between 3.3 and 3.7, most preferably 3.5.

[0092] Particularly preferred is a composition comprising:

[0093] - water 48.84%

[0094] - fructose 32.56%

[0095] - D.E. ginger 0.54%

[0096] - E.G. ginger 8.14%

[0097] - y-cyclodextrin 2.71%

[0098] - D.E. chamomile 4.07%

[0099] - lactic acid 0.70%

[0100] - citric acid 1 . 16%

[0101] - sodium lactate 1.16%

[0102] - vitamin B6 0.005% - xanthan 0.10%

[0103] - acacia gum 0.02%.

[0104] Advantageously, in contrast to JP 2015 231979 A which claims that a combination of two different cyclodextrins, y-cyclodextrin and maltosyl-cyclodextrin, must be used to avoid precipitation and bring a ginger extract, specifically black ginger extract, into solution, the present invention demonstrates that in reality, the use of y-cyclodextrin alone is sufficient to form stable complexes with the ginger actives.

[0105] ESEAIPI

[0106] The contents of the present paragraph, the examples given, and the method of preparation are intended as purely illustrative descriptions, which are not intended to limit the scope of the present invention.

[0107] The general method of preparing the composition according to the present invention is described below.

[0108] The composition according to the present invention can be made either by slavishly following the method described below or by slight modifications thereof.

[0109] Said slight modifications, to be considered within the reach of an average technician in the art, may relate to mixing times, order of addition of ingredients, temperature, and any other variable known to the person skilled in the art, without altering the result or extending the scope of the invention itself.

[0110] Molecular dynamics simulation of the inclusion of ginger active ingredients into y- cyclodextrins.

[0111] In order to evaluate the efficacy of molecular inclusion of active ginger compounds within y- cyclodextrins, in silico molecular dynamics experiments were prepared, choosing as a model a system (simulation cube) that included gamma-cyclodextrins and ginger compounds in a 1 : 1 ratio.

[0112] In more detail, the following were included in the simulation cube: y-cyclodextrins, [6]- gingerol, [6]-shogaol, [8]-gingerol, [8]-shogaol,

[0010] -gingerol,

[0010] -shogaol, water and ions. (Figure 3) The system was simulated for a total time of 150 ns allowing the molecular species to interact and aggregate.

[0113] At the end of the simulation, all ginger compounds were found to be suitable for interacting with gamma-cyclodextrins, forming stable complexes and showing different abilities to penetrate the oligosaccharide ring.

[0114] The stability is due to the hydrophobic properties of gingerols and shogaols, which, to avoid contact with water, penetrate into the (also hydrophobic) ring of cyclodextrins.

[0115] The results of the molecular dynamics model show that, [6]-gingerol and [6]-shogaol (Scheme 1), interact with y-cyclodextrins only at the level of the methoxyphenolic head. In fact, Figures 2 and 3 for [6]-gingerol and [6]-shogaol, respectively, show that the aromatic head remains trapped in the oligosaccharide ring while the alkyl chain remains exposed to the solvent instead.

[0116] Scheme 1: Left [6]-gingerol, right [6]-shogaol

[0117] As depicted in Figure 4, similar behavior in terms of the shape of the inclusion complex is found with [8]-gingerol (Scheme 2) while, contrary to expectations, [8]-shogaol (Scheme 2) generates a rather anomalous and unexpected interaction geometry' with y-cyclodextrin.

[0118] Scheme 2: Left [8]-gingerol, right [8]-shogaol

[0119] In fact, as shown in Figure 5, the cis unsaturation at position 8 of [8]-shogaol ensures the lipid tail a better twist, allowing the entire molecule to be housed in the ring.

[0120] Interaction differences also occur for the two structural analogs

[0010] -gingerol and

[0010] -shogaol (Scheme 3), which although similar as carbonaceous skeleton, show' totally different inclusion geometry.

[0121] Scheme 3: Left

[0010] -gingerol, right

[0010] -shogaol

[0122] In fact,

[0010] -gingerol totally penetrates inside the y-cyclodextrin ring and the interaction, as shown in Figure 6, occurs just below the head of the compound.

[0123] In contrast, in the case of

[0010] -shogaol, stabilization occurs exclusively through the tail end. (Figure 7)

[0124] Molecular dynamics simulation for evaluating the solubility of the active ingredients of ginger with and without y-cyclodextrins.

[0125] To test the ability of cyclodextrins to solubilize ginger compounds in water, three different simulations (System 1, System 2 and System 3) were developed with increasing concentration of gamma cyclodextrins.

[0126] • System 1 consisting of [6]-gingerol, [6]-shogaol, [8]-gingerol, [8]-shogaol,

[0010] -gingerol,

[0010] -shogaol, water and ions. System therefore in the absence of y-cyclodextrins.

[0127] • System 2 consisting of y-cyclodextrins, [6]-gingerol, [6]-shogaol, [8]-gingerol, [8]- shogaol,

[0010] -gingerol,

[0010] -shogaol, water and ions. In this system, active ingredients of ginger and y-cyclodextrins were added in 1 : 1 molar ratio.

[0128] • System 3 consisting of y-cyclodextrins, [6]-gingerol, [6]-shogaol, [8]-gingerol, [8]- shogaol,

[0010] -gingerol,

[0010] -shogaol, water, and ions. In this system, active ingredients of ginger and y-cyclodextrins were added in 1 :4 molar ratio.

[0129] All three systems were simulated under the same isotropic conditions for a total duration of 50 ns, after which it was found that:

[0130] In system 1, the ginger compounds tend to agglomerate into a hydrophobic core to avoid contact with water. In fact, as shown in Figures 8A and 8B, at the end of 50 ns of simulation, the formation of molecular aggregates is clearly visible.

[0131] In system 2, as shown in Figures 9A and 9B, the y-cyclodextrins manage to form inclusion complexes with both gingerols and shogaols, but the 1 : 1 ratio is not sufficient to avoid the formation of hydrophobic nuclei. Indeed, at the end of 50 ns, the formation of a molecular aggregate of ginger compounds with y-cyclodextrin inclusions only on the surface is still evident.

[0132] In system 3, the 4: 1 ratio of y-cyclodextrins to ginger compounds prevents the formation of the hydrophobic core observed in the other two systems. As shown in Figures 10A, 10B and 10C, at the end of 50 ns of simulation, no molecular aggregates are evident and the compounds are well distributed in the three-dimensional network of y-cyclodextrins. In fact, the excess amount of y-cyclodextrins allows the formation of both open and closed inclusion complexes.

[0133] In open ones, a host molecule interacts with a single y-cyclodextrin molecule, as shown in Figures 11 A and 1 IB.

[0134] In contrast, in closed ones, as well depicted in Figures 12A and 12B, a host molecule interacts with two y-cyclodextrins that enclose it within a “capsule.” It is precisely the second type of interaction that allows greater solubilization of the active compounds because it prevents interaction with other hydrophobic molecules.

[0135] In any case, dynamics allows us to verify that the three-dimensional network of y- cyclodextrins is a fluid, ever-changing system with inclusion complexes (y-cyclodextrin + host molecule) moving freely in the medium. At the macroscopic level, this ensures that the solution remains liquid, although locally aggregates of y-cyclodextrins are created.

[0136] Example 1

[0137] Evaluation of the effect of glycerol

[0138] Glyceric extracts were prepared using a fixed concentration of dried ginger (rhizome) of 5% (w / v). Glycerol was used at varying concentrations in water:

[0139] - 10% glyceric extract (E.G. 10)

[0140] - 50% glyceric extract (E.G. 50)

[0141] - 90% glyceric extract (E.G. 90)

[0142] Glycerol-free aqueous extract was used as a control to monitor oxidation of bioactive components (CTRL).

[0143] Briefly, 2.5 g of ginger (rhizome) was dissolved in a final volume of 50 mL, according to the above glycerol / water proportions, and kept stirring for one hour at room temperature. Subsequently, the samples were centrifuged, and the supernatant was transferred to a new 50 mL Falcon. In order to create an oxidizing action environment, 200 pL of 30% hydrogen peroxide (H2O2) was added to each sample. The extracts were then placed inside a climate chamber under the following conditions: temperature 40°C, humidity 75%, light 8:00-16:00. Reducing-acting polyphenols were quantified using the Folin-Ciocalteau method. The Folin- Ciocalteau (F-C) reaction is an electron transfer-based antioxidant assay that measures the reducing capacity of an antioxidant compound. The assay is widely used for the determination of total phenol / polyphenol content in foods of plant origin. The oxidizing reagent F-C reacts with reducing agents to form a vivid blue soluble complex, which can be translated into a numerical value by spectrophotometric measurement of absorbance at a wavelength of 760 nm. Absorbance is directly proportional to polyphenol content (Perez et al., 2023). Extracts were analyzed before being subjected to the above conditions (TO), after 4 days (T4) and after 7 days (T7) of treatment. Analysis of the content of total polyphenols in the samples tested showed differences in relation to the concentration of glycerol present. Figure 13 shows the trend in total polyphenol content (%) over time for each glyceric extract (E.G. 10, E.G. 50, E.G. 90). It is clearly observed that as the concentration of glycerol increases, the content of polyphenols with reducing activity tends to decrease more and more at day 4 (T4) and day 7 of treatment (T7) compared with freshly prepared extracts (TO). This finding suggests that glycerol exerts a protective action on the antioxidant activity of the polyphenols in ginger, which, in the absence of glycerol and under pro-oxidant conditions, would not be able to reduce the F-C reagent, since they are already oxidized.

[0144] The percentage differences in total polyphenols for each glyceric extract and control, between TO and T4 (beginning and mid-treatment) and between TO and T7 (beginning and end of treatment), are shown in Table 1.

[0145] Table 1. Percentage decrease in total polyphenol content from TO to T4 and from TO to T7 for each glyceric extract, including control.

[0146] After 4 days, there is a variable reduction in total polyphenol content for all samples: the higher the concentration of glycerol in the extract, the lower the loss compared to TO. This trend is further confirmed by treatment data after 7 days (T7), which show a percentage decrease in total polyphenols almost double that observed at T4. These numerical results visually support what has already been shown in Figure 13.

[0147] Preparation method

[0148] The operational steps for making the composition in liquid / gel form according to the present invention include in order:

[0149] • Load the required amount of water into the mixer, 30% of the total max.

[0150] • Turn on agitation and heating of the mixer.

[0151] • Add to the mixer: sodium lactate, lactic acid, citric acid, chamomile D.E.

[0152] • Mix Ginger E.G. (and ginger D.E., if any) separately with y-cyclodextrins for 10' and let stand for 20'.

[0153] The mixture should have a creamy consistency. If necessary, add water in amounts of 10% by weight to the total. Repeat addition of water until desired consistency is obtained.

[0154] • Add the newly obtained mixture of ginger extract and y-cyclodextrins to the blender.

[0155] • Under stirring, wait until the temperature reaches about 62°C and keep the mixer at this temperature for 30 minutes.

[0156] • Add fructose, xanthan and acacia gum to the mixer.

[0157] • Cool under stirring until the temperature reaches 30°C.

[0158] • Then take 500 ml of product from the mixer and dissolve the previously and appropriately weighed vitamin B6 in it.

[0159] • Leave it stirring for about 30 minutes until the desired product is obtained

[0160] Materials and methods

[0161] In order to execute the present invention and obtain the preferred embodiments according to the claimed scope of protection, it is necessary to be in possession of common laboratory glassware (e.g., beakers of various capacities), a homogenizer (30000 rpm max, 500 W) or the like, and a propeller mixer or the like. An expert in the field will have no difficulty in identifying similar instrumentation for carrying out the invention. Preparation of molecular dynamics systems

[0162] Systems were modeled using Chimera X software [1] and the dedicated online server Charmm-GUI [2], A random scattering of components with equal distribution of species in the simulation space was recreated for the initial positions of the molecules.

[0163] Molecular Dynamics Simulation

[0164] Molecular Dynamics simulations were performed with GROMACS 2020 software [3-4-5] in an isothermal-isobaric (NPT) ensemble and periodic boundary conditions. The CHARMM36 force field [6] was applied for ginger compounds, cyclodextrins, ions, and water molecules.

[0165] For each system, energy minimizations were first performed to eliminate unfavorable contacts with imposed positional constraints.

[0166] A two-stage simulation protocol was then applied: 1) equilibration phase (totaling 250 ps) at constant volume (NVT) with the application of Berendsen's thermostat [7] for temperature control; 2) production phase (totaling 50 ns) in the NPT ensemble with the application of Berendsen's algorithm for temperature and pressure coupling. The positional constraints to the gingerols, shogaols, and cyclodextrins, which were necessary in the equilibration phase to allow the water molecules to distribute properly in the system, were released during the production phase. The SETTLE [8] and LINCS [9] constraints were applied to the covalent bonds, and the timestep was set to 2 fs. Electrostatic interactions were calculated with the Ewald particle-mesh algorithm (PME)

[0010] with a cutoff in real space of 1.0 nm.

[0167] The temperature was maintained at 303.15 K for all 50 ns by applying the Nose-Hoover method [11-12] and the pressure was kept constant at 1 bar by isotropic coupling to a Parrinello-Rahman barostat

[0013] with compressibility set at 4.5 x 10'5bar'1.

[0168] Data Analysis

[0169] Analysis of the simulation data was conducted using the tools implemented by Gromacs.

[0170] Visual Molecular Dynamics software (VMD)

[0014] and UCSF Chimera X, (developed by the Resource for Biocomputing, Visualization, and Informatics, University of California, San Francisco, with support from the National Institutes of Health R01-GMJ29325 and the Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases) were used for dynamics visualizations and image export. Preferred example of composition

[0171] A preferred embodiment of the present invention is a composition comprising water 48.84%, fructose 32.56%, D.E. ginger 0.54%, E.G. ginger 8.14%, y-cyclodextrin 2.71%, D.E. Chamomile 4.07%, lactic acid 0.70%, citric acid 1.16%, sodium lactate 1.16%, vitamin B6 0.005%, xanthan 0.10%, acacia gum 0.02%.

[0172] References

[0173] [1] UCSF ChimeraX: Tools for structure building and analysis. Meng EC, Goddard TD, Pettersen EF, Couch GS, Pearson ZJ, Morris JH, Ferrin TE. Protein Sci. 2023 Nov;32(ll):e4792.

[0174] [2] S. Jo, T. Kim, V.G. Iyer, and W. Im (2008) CHARMM-GUI: A Web-based Graphical User Interface for CHARMM. J. Comput. Chem. 29:1859-1865.

[0175] [3] H. Bekker, H.J.C. Ber endsen, E.J. Dijkstra, S. Achterop, R. van Drunen, D. van der Spoel, A. Sijbers, and H. Keegstra et al., “Gromacs: A parallel computer for molecular dynamics simulations” ; pp. 252-256 in Physics computing 92. Edited by R. A. de Groot and J. NadrchaL World Scientific, Singapore, 1993

[0176] [4] M. J. Abraham, T. Murtola, R. Schulz, S. Pall, J. C. Smith, B. Hess, E. Lindahl GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers SoftwareX 1 (2015) pp. 19-25

[0177] [5] S. Pall, M. J. Abraham, C. Kutzner, B. Hess, E. Lindahl Tackling Exascale Software Challenges in Molecular Dynamics Simulations with GROMACS In S. Markidis & E. Laure (Eds.), Solving Software Challenges for Exascale 8759 (2015) pp. 3-27

[0178] [6] CHARMM: The Biomolecular Simulation Program. J. Comput. Chem. 30:1545-1614 J. Lee, X. Cheng, J.M. Swails, M.S. Yeom, P.K. Eastman, J. A. Lemkul, S. Wei, J. Buckner, J.C. Jeong, Y. Qi, S. Jo, V.S. Pande, D.A. Case, C.L. Brooks HI, A.D. MacKerell Jr, J.B. Klauda, and W. Im (2016) [7] Ber endsen, H. J. C, Postma, J. P. M., Vangunsteren, W. E, Dinola,A. & Haak, J. R. Molecular-dynamics with coupling to an external bath. J. Chem. Phys. 81, 3684- 3690 (1984).

[0179] [8] Miyamoto, S. & Kollman, P. A. Settle — an analytical version of the shake and rattle algorithmfor rigidwater models. J. Comput. Chem. 13, 952 962 (1992).

[0180] [9] Hess,B., Bekker,H., Ber endsen, H. J. C. & Fraaije, J. G.E.M. LINCS:a linear constraint solver for molecular simulations. J. Comput.Chem. 18, 1463 1472 (1997).

[0181]

[0010] Essmann, U. et al. A smooth particle mesh Ewald method. J. Chem.Phys. 103, 8577 8593 (1995).

[0182]

[0011] Braga, Carlos; Travis, Karl P. (2005-09-30). "A configurational temperature Nose- Hoover thermostat". The Journal of Chemical Physics. 123 (13): 134101. Bibcode:2005JChPh.l23m4101B. doi: 10.1063 / 1.2013227

[0183]

[0012] Patra, P. K.; Bhattacharya, B. (2014-02-11). "A deterministic thermostat for controlling temperature using all degrees of freedom ". The Journal of Chemical Physics. 140 (6): 064106. Bibcode : 2014JChPh.l40f4106P. doi: 10.1063 / 1.4864204

[0184]

[0013] Parrinello, M. & Rahman, A. Polymorphic transitions in single-crystals — a new molecular-dynamics method. J. AppL Phys. 52, 7182 7190 (1981).

[0185]

[0014] ffl. Humphrey, A. Dalke, and K. Schulten, J. Mol. Graph. 14, 33 (1996). https: / / doi.org / ! 0.1016 / 0263-7855(96)00018-5 http: / / www.ks.uiuc.edu / Research / vmd /

Claims

Claims1. Composition comprising y-cyclodextrin and ginger extract in a solvent suitable for food use wherein the weight ratio in the composition between said y-cyclodextrin and said ginger extract is in the range of 0.1-3, preferably 0.333, and said ginger extract is a glyceric extract in an amount preferably between 4% and 16%.

2. Composition according to claim 1 wherein the solvent is water.

3. Composition according to any one of the preceding claims further comprising at least one thickener.

4. Composition according to any one of the preceding claims further comprising at least one of preservatives, pH modulators, vitamins, natural extracts, sweeteners and / or sugars.

5. Composition according to any one of the preceding claims having a pH between 3.2 and 4.9, preferably between 3.3 and 3.7, preferably 3.5.

6. Composition according to any of the preceding claims formulated in liquid or gel form.

7. Composition according to any of the preceding claims wherein the solvent is water, the ginger extract is a glyceric extract and further comprising fructose, chamomile D.E., lactic acid, citric acid, sodium lactate, vitamin B6, xanthan and acacia gum.

8. Composition according to the preceding claim comprising:- Water in an amount between 30% and 60%- Fructose in an amount between 0.00001% and 40%- E.G. ginger in an amount between 4% and 16%- y-cyclodextrin in an amount between 0.1% and 5%D.E. chamomile in an amount between 0.00001% and 8%- Lactic acid in an amount between 0.1% and 1.5%Citric acid in an amount between 0.5% and 1.8%Sodium lactate in an amount between 0.5% and 1.8%Vitamin B6 in an amount between 0.00001% and 0.02%Xanthan in an amount between 0.00001% and 4%Acacia gum in an amount between 0.00001% and 0.05%.

9. Composition according to any one of the preceding claims further comprising D.E. ginger in an amount between 0.00001% and 1%.

10. Composition according to any of the preceding claims comprising:- water 48.84% fructose 32.56%D.E. ginger 0.54%- E.G. ginger 8.14%- y-cyclodextrin 2.71%D.E. chamomile 4.07% lactic acid 0.70% citric acid 1.16% sodium lactate 1.16%- vitamin B6 0.005%- xanthan 0.10% acacia gum 0.02%.

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