Resveratrol-based composition

Abstract

A resveratrol-based composition is herein described, which shows a surprising increase of solubility and / dispersibility of resveratrol and of its permucosal absorption. In particular, a composition is described comprising resveratrol (from dry extract of Poligonum cuspidatum), hydroxypropylcellulose, maltodextrin and sucrose esters, obtained by dry co- grinding of its components.

Description

[0001] RESVERATROL-BASED COMPOSITION

[0002] FIELD OF THE INVENTION

[0003] T h e present invention relates to a resveratrol-based composition, which exhibits a surprising increase in the solubility and / or dispersibility of resveratrol and its permucosal absorption. In particular, it refers to a composition comprising resveratrol, hydroxypropylcellulose, maltodextrin and sucrose esters, obtained by dry co-grinding of its components.

[0004] BACKGROUND OF THE INVENTION

[0005] Resveratrol (trans-3,5,4'-trihydroxysystylbene) is a polyphenol with a stylbenic structure, contained in red grape and in higher concentration in the root of Polygonum cuspidatum, a plant used in traditional Chinese and Japanese medicine.

[0006] The discovery of the protective effects of red wine (the so-called "French paradox") in 1992 followed numerous pre-clinical and clinical research projects, which demonstrated the antioxidant, anti-inflammatory, cardioprotective, anti-cancer, neuroprotective and anti- angiogenic properties of resveratrol (see Baur J. A. et al., Nat. Rev. Drug Discov., 5(6), pp. 493-506, 2006; Smoliga J.M. et al., mol. Nutr. Food Res. Special issue: Resveratrol - 55, pp. 1129-1141, 2011; Vang O. et al., PLoS one, 6(6), 1-111-3, 2011). The reduction in glucose, triglyceride and inflammatory marker levels was observed by Timmers et al. which have hypothesized a correlation with the effects of caloric restriction (Timmers S. et al., Cell Metab., 14(5), pp. 612-22, 2011).

[0007] The low solubility of resveratrol limits its permucosal absorption (see Das S. et al., Pharm. RES., 12:29835, 2008). Moreover, resveratrol is rapidly converted into glucuronate and sulfated compounds: the poor bioavailability of resveratrol therefore affects its effectiveness and nutritional potential.

[0008] The improvement of the water solubility and therefore of the permucosal absorption of resveratrol appears to be a target necessary to express the healthy potential of this polyphenol.

[0009] Dry co-grinding is part of the grinding techniques traditionally used by the food industry and consists in associating an active ingredient with carefully selected food additives; this technique allows to reduce the size of the particles, increases the surface thereof and creates an organized mixture, in which the active ingredient physically interacts in a homogeneous manner with food additives. In particular, the hydrophilic components act in water, favoring the dispersibility of the active ingredient.

[0010] Dry co-grinding does not make use of solvents, requires short processing times and is carried out at room temperature, avoiding any degradation of the thermolabile nutrients / food ingredients.

[0011] This process, described in patent application W003 / 097012, allows to obtain ternary compositions made of active ingredient / carrier / auxiliary co-grinding substance, whose dispersibility and dissolution characteristics are significantly improved with respect to the corresponding binary active ingredient / carrier compositions.

[0012] Patent application W02007 / 009997 has shown that dry co-grinding of active substances poorly soluble in aqueous or organic environments with a hydrophilic substance or hydrophobic carrier, depending on the physico-chemical characteristics of the active substance under examination, in the presence of an auxiliary co-grinding substance, allows a considerable reduction in the co-grinding times and in the most mild operating grinding conditions, with undoubted advantages for the stability of the active ingredient. In particular, for antioxidant substances it has been found that the compositions obtained showed a significant increase in the antioxidant power with the same content of active ingredient in solution. This process applied to resveratrol allowed to obtain an increase in solubility with respect to resveratrol alone of about twice, using P-cyclodextrin and glycine in ternary or quaternary mixtures (see Table 3 of W02007 / 009997) with a resveratrol load of 15% by weight.

[0013] Co-grinding was subsequently used in particular to increase the solubility of CoQlO by dry grinding it with maltodextrin and sucrose esters (WO 2013 / 80028 corresponding to US 2014 / 322189) or with hydroxypropylcellulose (HPC) and sucrose esters (WO 2016 / 074800 corresponding to US 2017 / 319509), using polymeric additives.

[0014] EP 3193834 reports a water-soluble powder, comprising: a polyethylene glycol (PEG) derivative of vitamin E; a mixture of sugar fatty acid ester and a binder; and a non-polar ingredient, other than the PEG derivative of vitamin E. According to specific embodiments, the sugar fatty acid may be a sucrose ester, the binder may be a maltodextrin and the nonpolar ingredient may be resveratrol.

[0015] US 10898477 indicates a method of improving the bioavailability of nutraceutical compounds (such as for example resveratrol), comprising producing a mixture of the active compound with surfactants, oil and sustained release polymers (hydroxypropyl methyl cellulose or cyclodextrin). The composition is then converted into a water dispersible powder that can be formulated with other ingredients.

[0016] WO 2021 / 186471 reports stable, solid dosage forms comprising granules of polyphenol (such as for example resveratrol) and granules of transition metal ion (such as copper), each of the granules comprising at least one diluent (such as for example maltodextrin, cyclodextrins or cellulose derivatives).

[0017] A group of researchers from Perugia found that resveratrol supported on magnesium dihydroxide (Resv@MDH) represents an oral formulation of resveratrol with better gastric absorption and bioavailability than pure resveratrol (Rossana Giulietta langitti et al., Frontiers in Nutrition, vol. 7, 1-10, 2020).

[0018] Patent application EP40232461 relates to a solid composition containing an amorphous material poorly soluble in water (for example resveratrol), hydroxypropylmethylcellulose (HPMC) and a polysaccharide of five or more sugars other than HPMC, characterized by a series of properties detectable by X-ray diffractometry (XRD).

[0019] DESCRIPTION OF THE INVENTION

[0020] T h e main object of the present invention is to increase the dispersibility in water and the permucosal absorption of a dry extract of Polygonum cuspidatum titrated in resveratrol.

[0021] In particular, it has been found that by co-grinding the dry extract of Poligonum cuspidatum titrated in resveratrol with a combination of maltodextrin and hydroxypropylcellulose (HPC) in the presence of sucrose ester, a surprising increase in the dispersibility of resveratrol and its permucosal absorption is obtained.

[0022] It is therefore an object of the present invention a composition comprising resveratrol, hydroxypropylcellulose, maltodextrin and sucrose esters obtained by dry co-grinding of its components.

[0023] According to one aspect of the invention, each component is present in the dry co-ground composition of the present invention in an amount of between 2% and 50% by weight, preferably between 5% and 45% by weight.

[0024] In particular, resveratrol is preferably present in an amount of between 25% and 35% by weight. Hydroxypropylcellulose is preferably present in an amount of between 15% and 45% by weight.

[0025] Maltodextrin is preferably present in an amount of between 25% and 40% by weight.

[0026] The sucrose esters are preferably present in an amount ranging from 2% to 10% by weight. According to the present invention, the expression "dry extract of Poligonum cuspidatum titrated in resveratrol" refers to a dry extract of Poligonum cuspidatum with a resveratrol titer of between 20 and 98 weight percent.

[0027] According to a preferred aspect of the invention the dry extract of Poligonum cuspidatum is a titrated extract at 98% by weight in resveratrol, and is also indicated as resveratrol.

[0028] "Hydroxypropyl cellulose" (HPC) is considered an amphiphilic carrier.

[0029] The "sucrose esters" are compounds, which are obtained by esterification of the fatty acids or by trans-esterification of the methyl esters of the fatty acids with carbohydrates, in general sucrose and other polysaccharides. They are also referred to as sugar polyesters (or sugar poly esters) or saccharosic esters of fatty acids. Examples of sucrose esters are: sucrose monopalmitate, sucrose monostearate, sucrose dipalmitate, sucrose di stearate, sucrose alkylate or mixtures of two or more thereof.

[0030] "Maltodextrins" are polymers deriving from the starch hydrolysis process (usually corn starch). By means of industrial processes it is in fact possible to modify the chemical bonds that link monosaccharides in the polysaccharides, thus obtaining more or less complex carbohydrates. The maltodextrins thus obtained are soluble in water, have a pleasant taste and are easy to digest.

[0031] "Dry co-grinding" means a process, in which a mixture of the substances in the form of powders is dry ground, i.e. without the addition of solvents or mixtures thereof, in a suitable equipment, such as for example a ball mill, hammer mill, planetarium mill, vibrational mill, be it with a fixed body or with a rotating body. The powders can be premixed or mixed during the co-grinding itself. At the end of the dry co-grinding process, the obtained powder composition is discharged from the mill and optionally sieved, for example to eliminate any aggregates.

[0032] The compositions of the present invention may be used for the manufacture of food supplements, foods for special medical purposes, medical devices, nutri-cosmetic products, that is, those which combine oral administration with skin application.

[0033] A further object of the present invention is a food supplement containing the composition of the present invention in one of the previously illustrated forms.

[0034] The term "food supplement (FS)" means a food product intended to supplement the common diet and which constitutes a concentrated source of nutrients, such as vitamins and minerals, or other substances having a nutritional or physiological effect, in pre-dosed forms (see also Directive 2002 / 46 / EC of 10 June 2002 and DLG 21 May 2004 No 169 Art. 2).

[0035] It is also an object of the present invention to provide a food for special medical purposes (FSMP) containing the composition of the present invention in one of the previously illustrated forms.

[0036] The term "food for special medical purposes (FSMP)" means as defined in the EU Regulation (No 609 / 2013), as well as in the guidelines issued by EFSA (European Food Safety Authority), entitled "Scientific and technical guidance on food for special medicinal products in the context of Article 3 of Regulation (EU) No 609 / 2013" - EFSA Journal 2015; 13(11) :430. In particular, this standard definition is divided into three points:

[0037] 1 ) a food product expressly processed or formulated and intended for the dietetic management of patients, including infants, to be used "under medical supervision" (medical supervision);

[0038] 2) intended for the complete or partial feeding of patients with limited, disturbed or altered capacity to take, digest, absorb, metabolize or eliminate common foods or certain nutrients contained therein or metabolites, or with other nutritional requirements determined by clinical conditions;

[0039] 3) the dietary management of which cannot be carried out exclusively with the modification of the normal diet. To be proposed and framed as FSMP, a product must meet the three points of the previous definition.

[0040] For the purposes of the distinction with FS, it should also be pointed out that, while the latter products comply with the standard definition of Directive 2002 / 46 / EC, they have only "physiological" beneficial effects for the supply of substances other than nutrients without any involvement in the constitution of the food ration (for example, products based on plant extracts), FSMP must necessarily have a "nutritional" role as constituents of a food ration to meet the nutritional needs of patients under specific nutritional vulnerability conditions.

[0041] It is also an object of the present invention to provide a medical device containing the composition of the present invention in one of the previously illustrated forms.

[0042] The term "medical device" means a product, used alone or in combination intended by the manufacturer to be used on man for the purposes of:

[0043] • diagnosis, prevention, control, therapy or attenuation of a disease;

[0044] • diagnosis, control, therapy, attenuation or compensation of a wound or handicap;

[0045] • study, substitution or modification of the anatomy or of a physiological process; whose main action desired in or on the human body is not achieved by pharmacological, immunological or by metabolism means, but whose function can be assisted by these means (see Directive 93 / 42 / EEC of 14 June 1993 concerning medical devices and its subsequent amendments).

[0046] As regards the excipients and / or diluents usable in the compositions according to the invention to be put on the market, reference should be made to what is widely reported in the literature and well known to those skilled in pharmaceutical technologies.

[0047] The pre-dosed forms are meant to be the usual pharmaceutical forms or formulations [see for example principles of pharmaceutical technology, Paolo Colombo, Marco Adami, et al, CEA, 2015] made by mixing one or more substances with nutritional or physiological effect with suitable inert excipients to allow the technical realization of the finished product.

[0048] Considering the release time of the active components, they can also be classified in conventional, either immediate release, or modified release, i.e. prolonged, delayed or repeated.

[0049] Finally, the single dose and multidose pharmaceutical forms can be mentioned, which must be dosed by the patient by means of appropriate measuring or dropping measures.

[0050] In the embodiment of supplements, the composition of the present invention can also be associated, assembled or mixed with one or more substances such as, for example, nonlimiting, those belonging to the groups listed below:

[0051] - vitamins;

[0052] - minerals or metals;

[0053] - substances having nutritional or physiological effect;

[0054] - substances and / or preparations or plant extracts; and

[0055] - prebiotics and probiotics.

[0056] By the expression "associating", "assembling" or "mixing" it is meant that one or more of the substances belonging to the groups listed above are added to the compositions of the present invention, by the formulator skilled in the art desirous of obtaining a particular nutritional or physiological effect, so that the final formulation, to all the effects, is added to the compositions of the present invention. It comprises one of the compositions of the present invention itself and one or more substances belonging to the groups listed above.

[0057] A recent review (Leyane T. et al., in. J. mol. Sci., 23,7273, 2022) shows that the excessive production of ROS (Reactive Oxygen Species) results in the destruction of nucleic acids and proteins, altering the cell structure and limiting its functionality. The progression of the aging process and various chronic degenerative syndromes can be controlled by strengthening the antioxidant defense system and / or by counteracting the deleterious repercussions of high levels of ROS.

[0058] In the following examples we will show how the compositions of the present invention exhibit a surprisingly higher antioxidant activity than resveratrol.

[0059] The compositions of the invention therefore contribute to the creation of a "cellular antioxidant climate", which favors the action of complementary nutrients, such as, in particular, citicoline, acetyl -carnitine and lipoic acid.

[0060] The citicoline, consisting of ribose, cytosine, pyrophosphate and choline, is physiologically present in the cells, where it acts as an intermediate compound in the biosynthesis of phosphatidylcholine and acetylcholine:

[0061] - phosphatidylcholine represents one of the main components of the cell membranes, of which it regulates fluidity, integrity and permeability.

[0062] - acetylcholine is an important neurotransmitter that acts at the level of the central and peripheral nervous system.

[0063] Acetyl L-carnitine is the acetyl ester of L-camitine and is an important element in energy metabolism, since it transports fatty acids from the cytoplasm to the mitochondria, where they are transformed into ATP (Adenosine TriPhosphate) through oxidative phosphorylation. Acetyl L-carnitine improves cholinergic functions and performs an antioxidant action protecting the brain from the neurotoxicity of beta-amyloid. Numerous clinical studies show the efficacy of the use of acetyl L-camitine in cognitive disorders.

[0064] Lipoic acid is used in the prevention of diabetes, in polyneuropathy and as scavenger of ROS, it restores intracellular levels of glutathione which tend to decrease with aging.

[0065] The following examples illustrate the invention without limiting it and refer to the following tables. Comparative examples of resveratrol co-ground with only one or two components are also reported to demonstrate the unexpected advantages of the present invention over such compositions. EXAMPLES

[0066] The dry extract of Poligonum cuspidatum titrated to 98% in resveratrol (the parts of which are those authorized by Annex 1 to DM 10 August 2018, as amended by the Executive Decree 26 July 2019), hereinafter referred to as resveratrol, has been obtained from usual suppliers / dealers [such as, by way of example only, not exhaustive: Farezis Pharma Sri of Milan; Nutraceutica di Monterenzio (BO)].

[0067] The excipients have also been obtained from usual suppliers / dealers [such as by way of example only not exhaustive: Products Gianni Sri, Milano; A.C.E.F. Spa Chemical and pharmaceutical Company, Fiorenzuola d'Arda (PC)].

[0068] EXAMPLE 1

[0069] Resveratrol / HPC / maltodextrin / sucrose ester in weight percent ratio

[0070] 25 / 45 / 25 / 5

[0071] For the preparation of the composition of this example, 30 g of a mixture containing resveratrol (7.5 g) / HPC (13.5 g) / maltodextrin (7.5 g) / sucrose ester (1.5 g), obtained using a rotary-body mixer, were loaded into ajar of a planetary mill and co-ground for 30 minutes at a speed of 200 rpm. At the end of the process, the product in the form of fine powder was discharged and sieved. A co-milled resveratrol / HPC / maltodextrin / sucrose ester was obtained in a weight percent ratio of 25 / 45 / 25 / 5 with a resveratrol titer of 25% by weight.

[0072] EXAMPLE 2

[0073] Resveratrol / HPC / maltodextrin / sucrose ester composition in weight percent ratio

[0074] 30 / 35 / 33 / 2

[0075] For the preparation of the composition of this example, 30 g of a mixture containing resveratrol (9 g) / HPC (10.5 g) / maltodextrin (9.9 g) / sucrose ester (0.6 g), obtained using a rotary-body mixer, were loaded into a jar of a planetary mill and co-ground for 30 minutes at a speed of 200 rpm. At the end of the process, the product in the form of fine powder was discharged and sieved. A co-milled resveratrol / HPC / maltodextrin / sucrose ester in a weight percent ratio 30 / 35 / 33 / 2 was obtained with a resveratrol titer of 30% by weight.

[0076] EXAMPLE 3

[0077] Resveratrol / HPC / maltodextrin / sucrose ester ratio 35 / 20 / 35 / 10

[0078] For the preparation of the composition of this example, 30 g of a mixture containing resveratrol (10.5 g) / HPC (6 g) / maltodextrin (10.5 g) / sucrose ester (3.0 g), obtained using a rotary-body mixer, were charged into a jar of a planetary mill and co-ground for 30 minutes at a rate of 200 rpm. At the end of the process, the product in the form of fine powder was discharged and sieved. A co-milled resveratrol / HPC / maltodextrin / sucrose ester was obtained in a weight percent ratio of 35 / 20 / 35 / 10 with a resveratrol titer of 35% by weight.

[0079] EXAMPLE 4

[0080] Resveratrol / HPC / maltodextrin / sucrose ester ratio 35 / 15 / 40 / 10 For the preparation of the composition of this example, 30 g of a mixture containing resveratrol (10.5g) / HPC (4.5 g) / maltodextrin (12 g) / sucrose ester (3 g), obtained using a rotary-body mixer, were loaded into a jar of a planetary mill and co-ground for 30 minutes at a speed of 200 rpm. At the end of the process, the product in the form of fine powder was discharged and sieved. A co-milled resveratrol / HPC / maltodextrin / sucrose ester was obtained in a weight percent ratio of 35 / 15 / 40 / 10 with a resveratrol titer of 35% by weight.

[0081] COMPARATIVE EXAMPLE 1

[0082] Resveratrol / HPC / sucrose ester composition in a ratio 30 / 68 / 2

[0083] For the preparation of the composition of such example, 30 g of a mixture containing resveratrol (9 g) / HPC (20.4 g) / sucrose ester (0.6 g), obtained using a rotary-body mixer, were loaded into a jar of a planetary mill and co-ground for 30 minutes at a speed of 200 rpm. At the end of the process, the product in the form of fine powder was discharged and sieved. A co-ground resveratrol / HPC / sucrose ester was obtained in a percentage by weight ratio of 30 / 68 / 2 with a 30% by weight resveratrol title.

[0084] COMPARATIVE EXAMPLE 2

[0085] Resveratrol / maltodextrin / sucrose ester composition in a percentage by weight ratio of 30 / 68 / 2

[0086] For the preparation of the composition of this example, 30 g of a mixture containing resveratrol (9 g) / maltodextrin (20.4 g) / sucrose ester (0.6 g), obtained using a rotary-body mixer, were loaded into a jar of a planetary mill and co-ground for 30 minutes at a speed of 200 rpm. At the end of the process, the product in the form of fine powder was discharged and sieved. A co-milled resveratrol / HPC / maltodextrin / sucrose ester was obtained in a weight percent ratio of 30 / 68 / 2 with a resveratrol titer of 30% by weight.

[0087] COMPARATIVE EXAMPLE 3

[0088] Resveratrol / maltodextrin composition in weight percent ratio 30 / 70

[0089] For the preparation of the composition of this example, 30 g of a resveratrol-containing mixture (9 g) / maltodextrin (21 g), obtained using a rotary-body mixer, were loaded into ajar of a planetary mill and co-ground for 30 minutes at a speed of 200 rpm. At the end of the process, the product in the form of fine powder was discharged and sieved. A co-ground resveratrol / maltodextrin was obtained in weight percent ratio 30 / 70 with a resveratrol titer of 30% by weight.

[0090] COMPARATIVE EXAMPLE 4

[0091] Resveratrol / HPC ratio 30 / 70 for the preparation of the composition of such example, 30 g of a mixture containing resveratrol (9 g) / HPC(21 g), obtained using a rotary -body mixer, were loaded into a jar of a planetary mill and co-ground for 30 minutes at a speed of 200 rpm. At the end of the process, the product in the form of fine powder was discharged and sieved. A resveratrol / HPC co-ground was obtained in weight percent ratio 30 / 70 with a resveratrol titer of 30% by weight.

[0092] COMPARATIVE EXAMPLE 5

[0093] Resveratrol / HPC / maltodextrin composition in weight percent ratio 30 / 5 / 65

[0094] For the preparation of the composition of such example, 30 g of a mixture containing resveratrol (9 g) / HPC (1.5 g) / maltodextrin (19.5 g), obtained using a rotary-body mixer, were loaded into a jar of a planetary mill and co-ground for 30 minutes at a speed of 200 rpm. At the end of the process, the product in the form of fine powder was discharged and sieved. A co-milled resveratrol / HPC / maltodextrin was obtained in a weight percent ratio of 30 / 65 / 5 with a resveratrol titer of 30% by weight.

[0095] COMPARATIVE EXAMPLE 6

[0096] Resveratrol / HPC / maltodextrin ratio 30 / 65 / 5

[0097] For the preparation of the composition of such example, 30 g of a mixture containing resveratrol (9 g) / HPC (19.5 g) / sucrose ester (1.5 g), obtained using a rotary-body mixer, were loaded into a jar of a planetary mill and co-ground for 30 minutes at a speed of 200 rpm. At the end of the process, the product in the form of fine powder was discharged and sieved. A co-milled resveratrol / HPC / maltodextrin was obtained in a weight percent ratio of 30 / 65 / 5 with a resveratrol titer of 30% by weight.

[0098] EXAMPLE 5

[0099] Determination of water dispersibility

[0100] The water dispersibility at 25°C of some compositions of the present invention was evaluated with respect to some comparative compositions containing only some of the excipients.

[0101] The determination of dispersibility is a significant element of the present invention, in view of the fact that some compositions do not disperse well in water at times compatible with their use in forms, such as water-soluble sachets, orosoluble or stick packs, which are gaining a growing favor from consumers, but just put in water tend to form agglomerates, which then tend to disperse within 60 minutes. Other compositions, on the other hand, poured into water are dispersed immediately forming a stable milky emulsion, without agglomerates or precipitates.

[0102] The dispersibility determination was therefore carried out by placing an excess of the sample in water at 25°C, such as to form a bottom body, keeping it under stirring with a magnetic anchor.

[0103] Moreover, after 2 minutes and after 60 minutes the quantity of resveratrol is determined, which passes into solution, by centrifuging, filtering and possibly diluting the samples, if necessary.

[0104] The following Table 1 shows the amounts of resveratrol in pg / ml found in the aqueous solution after 2 minutes and after 60 minutes of stirring. The increase of this quantity with respect to the resveratrol as such is also reported. A visual evaluation of the dispersibility of the compositions in water is also indicated after 2 minutes of stirring. For each tested composition 75 mg equivalent resveratrol were poured into 20 ml water. TABLE 1

[0105] 75 mg resveratrol equivalents in 20 ml water

[0106] From the data reported in Table 1 it emerges that the best results in terms of solubility at 60 minutes and at 2 minutes and of visual dispersibility evaluation are obtained with the quaternary compositions, i.e. comprising resveratrol, hydroxypropylcellulose (HPC), maltodextrin (MDX) and sucrose ester. With such compositions it is possible to obtain surprisingly an increase in the solubility of at least about 4 times with respect to the resveratrol, guaranteeing a dispersibility in water even after 2 minutes more than satisfactory even with high percentages of resveratrol "load" (up to 35%).

[0107] EXAMPLE 6

[0108] Evaluation of the antioxidant activity

[0109] The antioxidant activity of the composition prepared in EXAMPLE 2 (hereinafter also called "Resveplus") was determined in comparison with the resveratrol as such, after evaluating the phenolic content (TPC) expressed as gallic acid equivalent (GAE), with the following tests, using doses of equimolecular Resveplus with respect to resveratrol as such:

[0110] DPPH Test (l, l-diphenyl-2-picrylidrazil) as described by Kumaran A. et al. (Food Chemistry, 97, pp. 109-1 14, 2006). The Resveplus samples were added to 2 mL of 0.1 mm DPPH solution. After stirring for 10 seconds, the mixtures were incubated at room temperature in the dark for 30 minutes; subsequently the absorbance at nm 517 was measured. The trolox calibration curve (Trolox is 6-hydroxy-2,5,7,8-tetramethylchroman-2- carboxylic acid) was plotted as a function of the percentage of free radical scavenging activity of DPPH. The results were expressed as milligrams of TE (Trolox Equivalents - a unit of measure of the antioxidant force based on Trolox) per gram of dry weight of the sample (mg TE / g DW).

[0111] CUprac Test as developed by Apak R. et al. (Method. J. Agric. Food Chem. 2004, 52, pp. 7970-7981, 2004). The Resveplus samples were added to 10 mL of 10 mm copper chloride, 7.5 mm neocuproine and 1 M ammonium acetate to pH 7. 1 ml of distilled water was immediately added to the mixture to bring the final volume to 4.1 ml. After 30 minutes of incubation at room temperature, the absorbance at 450nm was read.

[0112] ABTS test as described by Miller N. et al. (Clin. Skiing. (1993) 84 (4), pp. 407-412, 1993) based on the production of the ABTS radical cation by activation of methymoglobin with hydrogen peroxide in the presence of ABTS [2,2'-azinobis-(3-ethylbenzothiazolin-6-sulfonic acid)], with or without antioxidants. Thus, the antioxidants stop the ABTS+radical [2,2-azino- bis(ethylbenzene-thiazolin-6-sulfonic acid)], leading to a decrease in absorbance, which is detected by the antioxidant combination of the antioxidant with the radicals at different times. This test completes the previous tests, since, being carried out in an aqueous environment, it excludes any bias due to the presence of organic solvents.

[0113] The following Table 2 summarizes the results obtained:

[0114] TABLE 2

[0115] From the evaluation of the data reported in Table 2, it emerges that the antioxidant activity of Resveplus with respect to that of resveratrol is significantly and surprisingly superior in the three models of antioxidant activity considered. EXAMPLE 9

[0116] Evaluation of the kinetics.

[0117] Permucosal absorption of Resveplus in comparison with the resveratrol as such [CAS 501360] was tested on human oral epithelium reconstituted, in triplicate, at three times (6, 24 and 48 hours) with Franz cells.

[0118] The determination was carried out only in the cellular subnatant by HPLC / DAD analysis.

[0119] At the end of the exposure, the membrane integrity was evaluated by evaluating the passage of a fluorescent marker with respect to the untreated control.

[0120] The two products (Resveplus and Resveratrol) were applied to the human oral epithelium reconstituted in vitro at the same concentration calculated on the basis of the actual resveratrol concentration in Resveplus. Since resveratrol in Resveplus is 30%, resveratrol was applied as 300 mg / cm2, while Resveplus was applied to the concentration of 1 g / cm2. Above the two powders an artificial saliva volume was aliquoted.

[0121] Bearing in mind that the passages through the reconstituted human oral epithelium of resveratrol are below 1% of the amount applied, the evaluation of the permucosal absorption kinetics is based on the evaluation of the Resveplus passage difference with respect to this intrinsic limit of resveratrol; the significance of the data relating to the passage of Resveplus with respect to the data relating to the passage of resveratrol must therefore be evaluated.

[0122] The amounts of resveratrol absorbed (in pg / cm2) as it passes through the reconstituted human oral epithelium at the three measurement times are shown in Table 3 below. For each time 4 measurements were made.

[0123] TABLE 3 The average values of the measurements for each time reported in Table 3 are reported in the following Table 4 together with the respective standard deviations.

[0124] TABLE 4

Claims

CLAIMS1. A composition comprising resveratrol, hydroxy propyl cellulose, maltodextrin and sucrose esters, obtained by dry co-grinding of its components.

2. The composition according to claim 1, wherein each component is present at an amount comprised between 2% and 50% by weight, optionally between 5% and 45% by weight.

3. The composition according to claim 1, wherein resveratrol is present at an amount comprised between 25% and 35% by weight.

4. The composition according to claim 1, wherein hydroxy propyl cellulose is present at an amount comprised between 15% and 45% by weight.

5. The composition according to claim 1, wherein the maltodextrin is present at an amount comprised between 25% and 40% by weight.

6. The composition according to claim 1, wherein sucrose esters are present at an amount comprised between 2% and 10% by weight.

7. The composition according to claim 1, wherein resveratrol is present in a dry extract of Poligonum cuspidatum having a content in resveratrol comprised between 20% and 98% by weight.

8. The composition according to claim 1, comprising a dry extract of Poligonum cuspidatum having a content in resveratrol of 98% by weight, hydroxy propyl cellulose, maltodextrin and sucrose esters, obtained by dry co-grinding of its components.

9. A food supplement comprising the composition according to anyone of the claims from 1 to 8.

10. A medical device comprising the composition according to anyone of the claims from 1 to 8.

11. A food for special medical purposes comprising the composition according to anyone of the claims from 1 to 8.

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