ENZYMATIC MOLECULE MIMIMATING ANTIOXIDANT ACTIVITY

Abstract

Semiconductor colloids covalently grafted with an antioxidant, colloids being semiconductor colloids consisting of at least one element selected from the group comprising C, Si, Ge, Sn, S, Se, Te, B, N, P, As, Al, Sb, Ga, In, Cd, Zn, O, Cu, Cl, Pb, Tl, Bi, Ti, U, Ba, Sr, Li, Nb, La, I, Mo, Mn, Ca, Fe, Ni, Eu, Cr, Br, Ag, Pt, Hg, and their assemblages.

Description

The present invention relates to a complex in the form of an antioxidant grafted onto an electron reservoir that self-regenerates in the presence of photons. This may in particular be zinc oxide colloids that have been grafted with an antioxidant. The field of use of these colloids concerns in particular cosmetics, for example sunscreen, anti-aging compositions and food supplements. This can involve topical protection against the harmful effects of smoking, a diet rich in sugars or induced by exposure to ultraviolet radiation and / or polluting molecules present in the atmosphere. The skin is a constantly renewing organ that is subject to the effects of time. As the skin ages, skin cell renewal slows down. Older cells accumulate and give the appearance of a dull complexion, the skin dries out and thins. At the same time, changes occur in the dermis, a loss of fatty and muscle tissue, and therefore a loss of support. This is the process of skin aging. From a molecular perspective, skin aging is linked to an alteration in cell repair mechanisms. It is determined, on the one hand, by a genetically programmed individual "biological clock"; and on the other hand, by the cell's ability to resist oxidative damage caused by toxic substances called free radicals. This is intrinsic aging. At the same time, extrinsic aging is induced by environmental factors and behaviors specific to each individual. For example, these extrinsic factors include smoking, natural or artificial air pollutants, stress, sun exposure, alcohol consumption, and a diet high in sugar. Natural air pollutants refer to polluting molecules and particles generated by natural activities (volcanoes, minerals, oceans, etc.), such as sulfur dioxide or ozone. Artificial air pollutants are molecules and particles pollutants generated by human activities (factories, car engines, etc.) such as polycyclic aromatic hydrocarbons, heavy metals and pesticides. Some of these polluting molecules can cause inflammation, accelerated cellular aging, and even certain skin cancers. Among these compounds, persistent organic pollutants are among the most dangerous atmospheric pollutants for health. They generally attach to the surface of the skin. Following their absorption, a phenomenon of oxidative stress sets in and accelerates the skin aging process. Similarly, UV radiation leads, directly or indirectly, to the appearance of an imbalance between pro-oxidant elements and antioxidants, leading to the appearance of a phenomenon of oxidative stress within cells, for example skin cells. A diet high in sugars can lead to the formation of glycated proteins that cannot be destroyed or released from the cell. This results in increased production of free radicals, creating an imbalance in favor of prooxidant activity and thus physiological aging of the body. Alcohol and / or tobacco consumption alters cell metabolism and increases the production of free radicals, which creates an imbalance between the quantity of these free radicals produced and the antioxidant defense system. A free radical can be defined as a chemical species (molecule or atom) possessing one or more unpaired electrons in its outer shell. The most common are hydroxyl radicals (OH*), superoxide radicals (O2*), nitric oxide radicals (NO*), thiol radicals (RS*) or peroxyl radicals (RO2*'). If the atom of the free radical corresponds to an oxygen, the radicals will be called "reactive oxygen species" (ROS), such as singlet oxygen (^2) or the superoxide anion (O2-). Free radicals are unstable chemical molecules due to the unpaired electron(s) which gives them a high reactivity towards molecules surroundings. A free radical is a pro-oxidant element that is neutralized to the detriment of the neighboring molecule which in turn becomes a free radical and so on. The phenomenon spreads by chain reactions; this is oxidative stress. In practice, each pro-oxidant molecule requires the contribution of at least one or even two or three electrons to stabilize, that is to say to be neutralized. Every day, the skin is exposed to environmental aggressions. To defend itself against these attacks, the human body has developed defense systems through the use of enzymatic and / or non-enzymatic antioxidant agents. However, when an excessive amount of free radicals is generated, an imbalance sets in and the antioxidant defense system is overwhelmed, leading to damage to the skin tissue. Antioxidants can be defined as any substance which, present at low concentration relative to the oxidizable substrate, is capable of slowing down, at least, the oxidation of this substrate. This functional definition applies to a large number of substances, including enzymes with specific catalytic properties, but also small hydrophilic or liposoluble molecules. This great physicochemical variety allows the presence of antioxidants in all compartments of the organism, whether intracellular, membrane-bound or extracellular. For example, among the enzymatic antioxidants are listed superoxide dismutase or glutathione peroxidase and among the non-enzymatic antioxidants, we find vitamins (A, C, E), trace elements (selenium) or even proteins (ferritin). The activity of antioxidant agents slows down, delays, or prevents the prooxidant chain reaction initiated by free radicals. They are therefore prevention or termination agents capable of avoiding or trapping free radicals. In other words, antioxidants transform radicals into more stable compounds and block the propagation phase via the transfer of multi-electrons to prooxidant elements to partially or completely stabilize them. The complex of the invention exhibits antioxidant activity mimicking that of superoxide dismutase (SOD). SOD activity corresponds to a catalytic activity of the dismutation of the superoxide anion (O2*), into dioxygen (O2) and hydrogen peroxide (H2O2). The products of this reaction are considered free oxygen radicals, even though they do not have unpaired electrons, and turn out to be very reactive and harmful. For example, in the presence of iron, hydrogen peroxide will decompose and produce a hydroxyl radical OH* which is very toxic to most organic structures. These elements are then considered as secondary ROS produced by the reaction of the dismutation of the superoxide anion. Under physiological conditions, this dismutation is slow and leads to a prolonged half-life of the superoxide anion producing a deleterious oxidation of biological macromolecules by the production of said secondary ROS. However, the toxicity of these ROS is much higher than that of the superoxide anion. SOD will catalyze and therefore accelerate the dismutation of the superoxide anion to reduce the half-life of this element and therefore limit the pro-oxidant effects of the ROS produced secondary to the reaction of the dismutation of the superoxide anion. In addition, SOD will also allow the elimination of other ROS, for example, ^2 or ROO. Indeed, SOD is an enzyme capable of reducing a prooxidant by multi-electron transfer. In other words, SOD can react with all ROS to stabilize them and prevent or neutralize their prooxidant activity. This protein therefore provides a catalytic activity essential to the mechanism of elimination of ROS and therefore of oxidative stress. In cosmetics, many products aim to produce an antioxidant effect, also called an anti-free radical effect, to combat aging of intrinsic and / or extrinsic origin. Protection against oxidative stress, particularly induced by extrinsic factors, is currently based on the exploitation of antioxidant properties, for example, of plant extracts. However, these formulations are complex and involve a very large number of ingredients, including solvents and preservatives, whose safety is not always proven in the short or long term. Thus, despite their formulation, it appears that the effectiveness of the vast majority of the proposed solutions is not sufficient. Derivatives of antioxidant molecules are more commonly used in pharmaceutical formulations. However, they have the disadvantage of being less effective and less available compared to antioxidants in their native state and at equivalent doses. Conventional solutions for combating free radicals and their consequences require frequently renewed application to ensure a regular and continuous protective and / or restorative effect over time. Currently, no cosmetic composition offers a formulation comprising an enzymatic molecule whose activity is stable over time, to oxidize all types of ROS and reduce or eliminate oxidative stress. To solve this problem, the Applicant developed a complex mimicking the effect of SOD. This complex results from the combination of an antioxidant and colloids, serving as an electron reservoir, thus making it possible to fight against the harmful effects of all free radicals. More specifically, the present invention relates to semiconducting colloids covalently grafted, i.e. via at least one covalent bond, with an antioxidant. These semiconductor colloids advantageously consist of at least one element chosen from the group comprising C, Si, Ge, Sn, S, Se, Te, B, N, P, As, Al, Sb, Ga, In, Cd, Zn, O, Cu, Cl, Pb, Tl, Bi, Ti, U, Ba, Sr, Li, Nb, La, I, Mo, Mn, Ca, Fe, Ni, Eu, Cr, Br, Ag, Pt, Hg, and their assemblies. Advantageously, the semiconductor colloids according to the invention comprise two or three of these elements. These are: preferentially zinc oxide colloids, ZnO. Generally speaking, the term "semiconductor colloid" refers to a compound having an energy difference between the valence band and the conduction band that is small enough for an electron to pass from one to the other. For the purposes of the invention, "antioxidant" means an organic molecule capable of donating at least 1 electron or H* to a chemical species. According to the invention, this antioxidant carries at least one function capable of reacting with an available function present on the surface of the semiconductor colloids to create the complex according to the invention. Antioxidant grafting does not correspond to the formation of a shell. It is a grafting by the formation of covalent chemical bond(s) between the colloids and the antioxidant. The complex of the invention comprises two elements, respectively, a colloid and an antioxidant. The colloid acts as an electron reservoir, i.e. it is capable of transferring an electron to the antioxidant, due to its proximity, as long as the reservoir contains one and as long as the antioxidant is in demand. The electron thus transferred makes it possible to regenerate the anti-radical function of the antioxidant element. The complex of the invention thus exhibits an activity mimicking that of SOD, i.e. it is capable of reducing a pro-oxidant agent by means of several electrons. According to another feature, in the case of topical application, by means of exposure to electromagnetic radiation, for example ultraviolet (UV) rays, in particular between 280 and 400 nm in the UV-A and UV-B range, there will be electronic regeneration of the colloid by conversion of photonic energy into electrons. This means that the reservoir will have the capacity to indefinitely donate electrons to the antioxidant element. In synthesis, colloids constitute a reservoir of electrons allowing the regeneration of the anti-radical activity of the antioxidant which can thus react with as many free radicals as there are electrons available in the colloids and / or to oxidize and therefore neutralize all the radical compounds. This effect is linked to the proximity between the colloids and the antioxidant. Indeed, in the absence of grafting, the antioxidant, AntiOx, is not regenerated even when colloids are present in the reaction medium. Colloids, also referred to as "Col", are crystalline particles (non-amorphous form) with semiconducting properties resulting from the ordered stacking of molecules, for example ZnO molecules. These colloids can also be called "quantum dots" or nanocrystals. They can be in the form of a dispersion or a suspension of colloids in an aqueous medium. Colloids can be synthesized using conventional techniques, for example, the so-called "bottom-up" precursor growth approach. This synthesis route, commonly used in the field of nanomaterials, involves a nucleation step and a growth step from isolated atoms. It allows the size of the colloids to be controlled. For clarity, the term “Col / AntiOx” is used to designate the colloids according to the invention, i.e. colloids, for example of zinc oxide, grafted with an antioxidant. In addition, “AntiOx” designates the antioxidant grafted onto the colloids. The concept of grafting, or functionalization, of colloids is part of the general knowledge of those skilled in the art. Grafting, or functionalization, corresponds to the formation of covalent bonds between the antioxidant and the surface of the colloids. As already mentioned, these are not core / shell type colloids. Grafting provides the proximity necessary for multi-electron transfer from colloids to the antioxidant. Col / AntiOx colloids have the advantage of conferring a self-regenerating antioxidant effect in the presence of organic molecules, for example organic radicals or free radicals. Advantageously, the grafted AntiOx antioxidant is more stable. In other words, the half-life of the AntiOx antioxidant is increased. The presence of Col / AntiOx colloids prevents the formation of radical species secondary to the reaction, in particular singlet oxygen and / or peroxide. hydrogen. On the contrary, the compositions of the prior art do not block the formation of secondary radical compounds, which results in the formation of an imbalance between pro-oxidant and antioxidant agents, producing “secondary” oxidative stress and cellular damage. In other words, the Col / AntiOx colloids according to the invention neutralize any primary and / or secondary prooxidation activity. Generally speaking, colloids have an average size of the order of a few nanometers to a few tens of nanometers. Thus, the colloids have a size advantageously between 0.5 nm and 1000 nm, more advantageously between 10 nm and 100 nm, and even more advantageously of the order of 30 nm, the size being measured by DRX. XRD (X-ray diffraction) is a technique conventionally used to measure the size of crystals in the solid state. By size, we mean the largest dimension of the colloids (Col or Col / AntiOx), for example the diameter in the case of spherical colloids. This is the average size of grafted (Col / AntiOx) or non-grafted (Col) colloids. Indeed, the size of grafted Col / AntiOx colloids is generally included in the ranges of values ​​given above. If necessary, the person skilled in the art will be able to adapt the size of the non-grafted Col colloids. The Col and / or Col / AntiOx colloids are advantageously spherical in shape. Of course, grafting is not limited to grafting a single molecule of a single antioxidant onto a colloid. It involves grafting a multitude of molecules of at least one type of antioxidant AntiOx onto each nanocrystal, for example zinc oxide. The antioxidant AntiOx is a molecule capable of donating at least one electron. It can in particular be chosen from the group of compounds comprising at least one hydroxyl group (-OH) on at least one aromatic ring. Advantageously, the antioxidant AntiOx is a phenol, that is to say a phenyl comprising at least one hydroxyl group (-OH), or one of its derivatives or their complexes. The antioxidant AntiOx can in particular be chosen from the group comprising the compounds or their derivatives designated by the following INCI names: octadecyl di-t-butyl-4-hydroxyhydrocinnamate ; pentaerythrityl tetra-di-t-butyl hydroxyhydrocinnamate ; 2,6-Bis(l,l-dimethylethyl)-4-methylphenol ; bis-ethylhexyl hydroxydimethoxy benzylmalonate ; manganèse dioxide ; colloidal platinum ; tert-butylhydroquinone ; tetrabutyl ethylidenebisphenol ; sodium bisulfite ; sodium metabisulfite ; thioglycolic acid ; thiotaurine ; thioctic acid ; dilauryl thiodipropionate ; aminoethanesulfinic acid ; triethyl citrate ; sodium erythorbate ; sorbityl furfiiral ; erythorbic acid ; perillyl alcohol ; pyridyloxide t-butylnitrone ; ergothioneine ; melatonin ; acetyl cysteine ; cysteine ; lysine hydrochloride ; carnosic acid ; tyrosyl histidine HCl ; histidine hydrochloride ; pyridoxine serinate ; superoxide dismutase ; aminopropyl ascorbyl phosphate ; ascorbic acid ; ascorbic acid polypeptide ; ascorbyl dipalmitate ; ascorbyl glucoside ; ascorbyl linoleate ; ascorbyl methylsilanol pectinate ; ascorbyl palmitate ; ascorbyl tetraisopalmitate ;ascorbyl tocopheryl maleate ; trisodium ascorbyl palmitate phosphate ; disodium ascorbyl sulfate ; calcium ascorbate ; methylsilanol ascorbate ; sodium ascorbate ; sodium ascorbyl phosphate ; sodium ascorbyl / cholesteryl phosphate ; tetrahexyldecyl ascorbate ; magnésium ascorbyl phosphate ; tocopherol ; tocopheryl acetate ; tocopheryl linoleate ; tocopheryl linoleate / oleate ; tocopheryl nicotinate ; tocopheryl retinoate ; sodium tocopheryl phosphate ; dioleyl tocopheryl methylsilanol ; potassium ascorbyl tocopheryl phosphate ; dodecyl gallate ; epigallocatechin gallate EGCG ; propyl gallate ; ethyl ferulate ; ethylhexyl ferulate ; chitosan ascorbate ; chitosan glycolate ; apigenin ; tiliroside ; alpha-arbutin ; arbutin ; baicalin ; quercetin ; quercetin caprylate ; isoquercetin = isoquercitrin ; isoquercitrin ; diethylhexyl syringylidenemalonate ; dihydroxy methylchromone ; dimethoxy di-p-cresol ; dimethylmethoxy chromanol ; ethylbisiminomethylguaiacol manganèse chloride ;hesperidin methyl chalcone; kojic acid; kojic dipalmitate; madecassoside; asiaticoside; magnolol (5,5'-diallyl-2,2'-dihydroxybiphenyl); nordihydroguaiaretic acid; phenylethyl resorcinol; resveratrol; troxerutin (3',4',7-tris(hydroxyethyl)rutin); glucosylrutin; rutin (4H-l-benzopyran-4-one); disodium rutinyl disulfate; tetrahydrobisdemethoxydiferuloylmethane; ; tetrahydrodemethoxydiferuloylmethane; tetrahydrodiferuloylmethane; tococysteamide; totarol; hydroxydecyl ubiquinone; ubiquinone = coenz Q 10; carotenoids; lycopene; gallic acid; caffeic acid. The grafting can be carried out by reaction between an aldehyde group (-CHO) of the antioxidant agent AntiOx and the available functions present on the surface of said colloids Col. For example, the precursor of the antioxidant AntiOx can be 3-hy droxyb enzaldéhy de. According to another embodiment, the precursor of the antioxidant AntiOx may be caffeic acid or gallic acid. Advantageously, the colloids grafted with an antioxidant according to the invention are ZnO colloids grafted with 3-hydroxybenzaldehyde. Covalent grafting of the antioxidant AntiOx is carried out conventionally by reaction between a function of the antioxidant AntiOx or a precursor of the antioxidant AntiOx and functions available on the surface of the Col colloids. Colloids are not doped. Optionally, they may include a transition metal which is introduced during the synthesis of the colloids. Doping refers to the incorporation of an element into an already formed material. Incorporating an element during the synthesis of a material, i.e., before the material is formed, is not considered doping. The present invention also relates to the use of colloids grafted with at least one antioxidant. Col / AntiOx colloids can be used in a topical composition, for example a cosmetic composition but also in a cosmetic composition for non-therapeutic use. This composition is advantageously hydrophilic, micellar or Pickering (reverse form of a micellar composition). When the composition is for topical use, the formulation is advantageously free of lipophilic or hydrophilic, mineral or organic sunscreens. Indeed, their presence would lead to blocking the passage of necessary and essential UV rays. to achieve the antioxidant and self-regenerating effects as described. The cosmetic composition according to the invention may also comprise the usual adjuvants in the field considered. Of course, the person skilled in the art will take care to choose this, or these possible additional adjuvants or excipients, and / or their quantity, in such a way that the advantageous properties of the composition according to the invention are not, or not substantially, altered by the envisaged addition. Col / AntiOx colloids can also be used in a dietary supplement, for example a probiotic. When the complexes are used as a dietary supplement, the antioxidant element is only regenerated to the extent of the electron content of the reservoir, i.e., the colloid. Indeed, in this case, the colloids are not exposed to ultraviolet radiation, which prevents their regeneration. On the other hand, the AntiOx antioxidant benefits from the electron reservoir formed by the colloids, thus increasing its half-life and effectiveness. The dietary supplement containing Col / AntiOx may contain conventional excipients. It may, in particular, be in the form of capsules or tablets. The invention and the advantages resulting therefrom will emerge more clearly from the following figures and examples given to illustrate the invention and not in a limiting manner. DESCRIPTION OF FIGURES Figure 1 represents the diffractogram of ZnO colloids before functionalization with the antioxidant. The lines are indexed with the planes corresponding to the hexagonal ZnO structure. Figure 2 represents the DPPH kinetics for colloids functionalized with the antioxidant (Col / AntiOx) and for the antioxidant alone. Figure 3 represents the percentage of ABTS substrate degraded by colloids according to the invention exposed to UV rays or kept in the dark. Figure 4 illustrates the antioxidant activity of colloids functionalized with the antioxidant (Col / AntiOx) according to the invention compared to tocopherol, placed in the dark or exposed to UV. Figure 5 illustrates the antioxidant activity of colloids functionalized with an antioxidant (Col / AntiOx) according to the invention compared to other antioxidants. Figure 6 illustrates the inhibition of any primary and / or secondary prooxidation activity of the colloids functionalized with the antioxidant (Col / AntiOx) according to the invention compared to other antioxidants. EXAMPLES OF CARRYING OUT THE INVENTION 1 / Synthesis of colloids A zinc oxide precursor, such as zinc acetate, is mixed with a solvent or mixture of solvents, including benzyl alcohol, phenol, oleyl alcohol, butanol, propanol, isopropanol, water, tetrahydrofuran, ethanol, methanol, acetonitrile, toluene, PGMEA, PGPE, PGME, 2-methyl-l-propanol, or triethylene glycol monomethyl ether and sealed in an autoclave. The reaction mixture is heated to a temperature between 250 and 350°C. Once the reaction mixture reaches the set temperature, the temperature is maintained until ZnO crystallizes. Spherical zinc oxide nanocrystals of 7 nm diameter are harvested. 2 / Preparation of Col / AntiOx colloids (ZnO / 3-hydroxy benzaldehyde) Colloids according to the invention were prepared from the zinc oxide (ZnO) colloids obtained above and the antioxidant precursor 3-hydroxy benzaldehyde. ZnO / 3-hydroxy benzaldehyde particles are thus obtained. The small size of ZnO particles allows for a larger area to be covered and therefore allows for a greater number of antioxidant molecules to be grafted onto the surface. of each of the particles. The diameter of the ZnO colloids was measured using an X-ray diffractometer (XRD). The wavelength produced by the diffractometer corresponds to the Cu-Ka line equal to 1.54 Å. The other parameters used correspond to an accelerating voltage of 40 kV, an electric current of 40 mA and a Bragg-Brentano geometry. The diffractograms were measured on powder with a Cu-Ka source DRX in transmission. The diffractogram of colloids before functionalization (grafting) with the antioxidant is represented by Figure 1. 3 / Comparison of the kinetic time of the antioxidant activity of the Col / AntiOx colloids (ZnO / 3-hydroxy benzaldehyde) with that of a free antioxidant agent (3-hydroxy benzaldehyde) The rate of action of Col / AntiOx colloids was estimated by measuring the decomposition kinetics of 2,2-diphenyl-l-picrylhydrazyl (DPPH). DPPH is a molecule that retains its free radical status stably. This radical species absorbs light at 520 nm (violet color of the solution) and becomes colorless or pale yellow after neutralization by an antioxidant. It is thus possible to monitor the neutralization reaction by measuring the intensity of the absorption of the radical DPPH as a function of time. For this, two solutions in ethanol are prepared as follows: - a control solution containing DPPH with a concentration [DPPH]0 of 0.1 mol / L. - a test solution containing DPPH with a concentration [DPPH]0 of 0.1 mol / L and an antioxidant at a concentration such that 90% of DPPH is consumed after 2 hours (determination from IC50 measurements). Absorbance is measured using a UV / VIS / NIR spectrophotometer. 2.5 mL of solution is poured into a polystyrene tank (optical path length = 1 cm). The UV / visible absorption spectrum between 310 and 700 nm is measured for 300 seconds. The absorbance value at 520 nm allows the concentration of radical DPPH to be determined at a given time according to the Beer-Lambert equation: A520nm(T) - SdPPH-1-[DPPH]t According to this equation, A corresponds to the measured absorbance, 8dpph corresponds to the mass coefficient of DPPH, 1 (cm) corresponds to the optical path length through the sample and [DPPH]T (g / L) corresponds to the mass concentration of the sample. The curves obtained are refined according to a kinetic model which allows us to go back to the kinetic constant k and the half-life constant 1½ of the reaction. The graph demonstrating the speed of action of colloids functionalized with an antioxidant (ZnO / 3-hydroxy benzaldehyde) and that of the free antioxidant (3-hydroxy benzaldehyde), i.e. not grafted, is represented by figure 2. The results show that the ZnO / 3-hydroxy benzaldehyde antioxidant reacts more rapidly with DPPH than free 3-hydroxy benzaldehyde. 4 / Evaluation of the regeneration of the antioxidant activity of Col / AntiOx colloids 4.1 / Evaluation over time An 8 mM stock solution of ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) is incubated, at equal volume, with a 3 mM solution comprising metmyoglobin and hydrogen peroxide to produce a cationic ABTS radical. The resulting solution is diluted with phosphate buffer (0.2 M, pH 7.4) containing 150 mM NaCl to obtain an absorbance of 1.5 at 734 nm. Samples of 30 pL of ZnO / 3-hydroxy benzaldehyde (example 2 / ) dispersed at 240 g / L in water are added to 2970 pL of the 0.07 mM ABTS cationic solution in water, then stirred in the dark. After 30 minutes of incubation, ABTS is completely degraded. The solution obtained after this step of degradation of the entire ABTS substrate is separated: one part of the solution is placed in the dark, the other part is placed under UV irradiation. After 30 minutes of exposure (in the dark or under UV), 30 pL of a concentrated ABTS solution (7 mM) are added, then the solutions are again placed in the dark with stirring for 5 hours. The absorption is then measured every 30 minutes. The data are represented in Figure 3. The results show that the solution containing ZnO / 3-hydroxy benzaldehyde colloids and exposed to UV rays has a significantly higher ABTS degradation capacity than the solution containing ZnO / 3-hydroxy benzaldehyde colloids but kept in the dark. The ABTS degradation activity observed for the solution placed in the dark corresponds to the residual anti-radical activity inherent to the ZnO / 3-hydroxy benzaldehyde complex. Thus, after 120 minutes, 65% of ABTS is degraded by the solution exposed to UV radiation compared to 18% for the solution kept in the dark. In conclusion, the ZnO / 3-hydroxy benzaldehyde colloids according to the invention have the capacity to regenerate their antioxidant activity when exposed to UV radiation. 4.2 / Comparison with tocopherol The protocol for preparing solutions according to point 4.1 / was repeated with a concentration of ZnO / 3-hydroxy benzaldehyde colloids of 0.5 g / L and a concentration of tocopherol of 1.5 g / L. The solutions obtained are separated: one part of the solution is placed in the dark, the other part is placed under UV irradiation. After 30 minutes of exposure (in the dark or under UV), 30 pL of a concentrated ABTS solution (7 rnM) is added, and then the absorption is measured. The data are represented in Figure 4. The results show that the solution containing tocopherol exhibits the same ABTS degradation capacity (22%) after UV or dark exposure. The solution containing ZnO / 3-hydroxy benzaldehyde colloids exposed to darkness shows a capacity for degrading ABTS much higher than tocopherol (76%). This activity is further increased after UV exposure (89%). In conclusion, the ZnO / 3-hydroxy benzaldehyde colloids according to the invention possess a more effective anti-radical activity than a conventional antioxidant and an ability to regenerate the antioxidant activity when exposed to UV radiation. 5 / Evaluation of the antioxidant activity of colloids functionalized with antioxidants (ZnO / 3-hydroxy benzaldehyde) according to the invention The antioxidant activity of ZnO / 3-hydroxy benzaldehyde colloids was estimated by measuring the decomposition of 2,2-diphenyl-l-picrylhydrazyl (DPPH). The results are expressed in IC50 and / or in mg or pmol equivalent of the selected antioxidant sample. This method demonstrates the ability of a molecule to trap free radicals by transfer of electrons and / or protons resulting from oxidation phenomena. The protocol is as follows: - an ethanolic DPPH solution is prepared at 0.1 mM, - the samples (antioxidant) to be tested are prepared at different masses between 4 mg and 40 mg, - in a PMMA (poly(methyl methacrylate)) tank, 3900 pL of DPPH solution are mixed with 100 pL of the sample to be tested. The reaction is carried out under incubation at room temperature for 2 hours, then the absorbance at 515 nm is measured, - the percentage of antioxidant activity is plotted as a function of the concentration of the sample considered (in pM). The percentage of antioxidant activity is determined according to the following formula: % antioxidant activity = 1- (Aech / Abianc) x 100 Aech corresponds to the absorbance of the sample while Abianc corresponds to the absorbance of a solution without sample (100 pL ethanol + 3900 pL of a DPPH / ethanol solution). The resulting curve has a linear part and an asymptotic part. The linear area is of the form % AO = 7 / [sample]. This formula makes it possible to determine the sample concentration which allows 50% of the radicals present to be trapped, or to determine the IC50 in g / L (minimum inhibitory concentration at 50%) of the sample considered: CI50 =50 / X X representing the slope of the linear regression. The antioxidant activity of the colloids according to Example 2 (ZnO / 3-hydroxy benzaldehyde) was compared with that of conventional antioxidant agents listed below: - Sample of 30 pL diluted to 0.5 g / L are placed in 2970 L of a 0.07 mM ABTS solution, - Green tea extract containing more than 40% epigallocatechin gallate (EGCG), - 87.3% a-tocopherol + 12.7% soybean oil, - 100% L-ascorbic acid (Vitamin C), - 100% propyl gallate The results are shown in Figure 5. Figure 5 shows that the colloids according to the invention have an IC50 of approximately 0.03 g / L, which is much lower than that of conventional antioxidant agents. In other words, the concentration of ZnO / 3-hydroxy benzaldehyde according to the invention required to trap 50% of free radicals is lower than that of conventional antioxidants. Furthermore, an antioxidant activity higher than that of other antioxidants at concentration less than or equal to 0.15 g / L and similar at concentration greater than 0.15 g / L is observed. The antioxidant activity of ZnO / 3-hydroxy benzaldehyde is therefore superior to that of other antioxidant agents tested. 6 Evaluation of the protective power of the composition according to the invention against the generation of primary and secondary free radicals The study is carried out by the spin trapping method coupled with Electron Paramagnetic Resonance (EPR) spectroscopy to perform competitive trapping experiments using DIPPMPO (5-(Diisopropoxyphosphoryl)-5- methyl-l-pyrroline-N-oxide) as a trap molecule. This compound is conventionally used to detect and study the superoxide radical by this technique. The evolution of the signal intensity of the DIPPMPO-OOH adduct was monitored as a function of time in the presence or absence of creams. The method was evaluated by studying the 5 decomposition kinetics of a model radical (TEMPOL or l-Oxyl-2,2,6,6-tetramethyl-4-hydroxypiperidine) in the presence or absence of creams. Over the duration of the study, i.e. 20 minutes, no loss of TEMPOL signal was observed for the 4 experiments (control + 3 samples). Also, control analyses in the presence of Superoxide Dismutase (SOD) were carried out. Cream Inhibition at 3 minutes Inhibition at 5 minutes Inhibition at 10 minutes Inhibition at 15 minutes Sample A Complex according to the invention (ZnO / 3-hydroxybenzaldehyde) 100% 100% 100% 100% Sample B Mixture of antioxidants: squalane + tocopherol acetate + magnesium ascorbyl phosphate 48% 50% 45% 53% Sample C Mixture of antioxidants: tocopherol acetate + tocopherol + ergothioneine 20% 23% 37% 44% 10 Table 2: Percentage inhibition of the DIPPMPO-OOH signal as a function of time. The values ​​reported in the table are the average of 3 identical experiments (fluctuations being less than 10%). The inhibition kinetics are shown in Figure 6. Different superoxide radical scavenging properties are observed for each sample. Sample B shows a 48% decrease at 3 minutes (53% at 5 minutes) in the DIPPMPO-OOH adduct signal, suggesting a half inhibition of the oxidative activity. Sample C shows a 20% decrease at 3 minutes (44% at 5 minutes) in the DIPPMPO-OOH adduct signal, suggesting less effective inhibition than sample B. For the complex according to the invention, i.e. sample A (ZnO / 3-hydroxybenzaldehyde colloids), no signal corresponding to the DIPPMPO-OOH adduct is observed. Thus, all the superoxide radical produced has been trapped. During these experiments, the formation of an additional radical was observed (except for the sample according to the invention). According to the Applicant, it appears that this new radical originates from a Haber Weiss or Fenton reaction involving the presence of transition metal salts available to react with the superoxide radical or hydrogen peroxide (generated by the spontaneous dismutation of the superoxide radical). Thus, the hydroxyl radical would be generated and would react with the constituents of the cream to produce a new radical, called a secondary radical, observed in the form of an adduct on DIPPMPO. In conclusion, the colloids according to the invention have a superior capacity, compared to other compounds tested, to trap free radicals of the superoxide type. Also, no production of secondary radical species is observed with the colloids according to the invention, demonstrating total effectiveness in inhibiting ROS and therefore oxidative stress.

Claims

CLAIMS 1. Semiconductor colloids covalently grafted with an antioxidant, the colloids being semiconductor colloids consisting of at least one element selected from the group consisting of C, Si, Ge, Sn, S, Se, Te, B, N, P, As, Al, Sb, Ga, In, Cd, Zn, O, Cu, Cl, Pb, Tl, Bi, Ti, U, Ba, Sr, Li, Nb, La, I, Mo, Mn, Ca, Fe, Ni, Eu, Cr, Br, Ag, Pt, Hg, and assemblies thereof.

2. Colloids according to claim 1, characterized in that they have a size between 0.5 and 1000 nm, advantageously between 10 and 100 nm.

3. Colloids according to one of claims 1 to 2, characterized in that the antioxidant is chosen from the group comprising phenol or one of its derivatives and their complexes.

4. Colloids according to one of claims 1 to 3, characterized in that the antioxidant is chosen from the group comprising the compounds or their derivatives designated by the following INCI names: octadecyl di-t-butyl-4-hydroxyhydrocinnamate; pentaerythrityl tetra-di-t-butyl hydroxyhydrocinnamate; 2,6-Bis(1,1-dimethylethyl)-4-methylphenol; bis-ethylhexyl hydroxydimethoxy benzylmalonate; manganese dioxide; colloidal platinum; tert-butylhydroquinone; tetrabutyl ethylidenebisphenol; sodium bisulfite; sodium metabisulfite; thioglycolic acid; thiotaurine; thioctic acid; dilauryl thiodipropionate; aminoethanesulfmic acid; triethyl citrate; sodium erythorbate; sorbityl furfiiral; erythorbic acid; perillyl alcohol; pyridyloxide t-butylnitrone; ergothioneine; melatonin; acetyl cysteine; cysteine; lysine hydrochloride; carnosic acid; tyrosyl histidine HCl; histidine hydrochloride; pyridoxine serinate; superoxide dismutase; aminopropyl ascorbyl phosphate;ascorbic acid ; ascorbic acid polypeptide ; ascorbyl dipalmitate ; ascorbyl glucoside ; ascorbyl linoleate ; ascorbyl methylsilanol pectinate ; ascorbyl palmitate ; ascorbyl tetraisopalmitate ; ascorbyl tocopheryl maleate ; trisodium ascorbyl palmitate phosphate ; disodium ascorbyl sulfate ; calcium ascorbate ; methylsilanol ascorbate ; sodium ascorbate ; sodium ascorbyl phosphate ; sodium ascorbyl / cholesteryl phosphate ; tetrahexyldecyl ascorbate ; magnésium ascorbyl phosphate ; tocopherol ; tocopheryl acetate ; tocopheryl linoleate ; tocopheryl linoleate / oleate ; tocopheryl nicotinate ; tocopheryl retinoate ; sodium tocopheryl phosphate ; dioleyl tocopheryl methylsilanol ; potassium ascorbyl tocopheryl phosphate ; dodecyl gallate ; epigallocatechin gallate EGCG ; propyl gallate ; ethyl ferulate ; ethylhexyl ferulate ; chitosan ascorbate ; chitosan glycolate ; apigenin ; tiliroside ; alpha-arbutin ; arbutin ; baicalin ; quercetin ; quercetin caprylate ; isoquercetin = isoquercitrin ; isoquercitrin ; diethylhexyl syringylidenemalonate ; dihydroxy methylchromone ; dimethoxy di-p-cresol ; dimethylmethoxy chromanol ; ethylbisiminomethylguaiacol manganèse chloride ; hesperidin methyl chalcone ; kojic acid ; kojic dipalmitate ; madecassoside ; asiaticoside ; magnolol (5,5’-diallyl-2,2’-dihydroxybiphenyl) ; nordihydroguaiaretic acid ;phenylethyl resorcinol; resveratrol; troxerutin (3',4',7-tris(hydroxyethyl)rutin); glucosylrutin; rutin (4H-l-benzopyran-4-one); disodium rutinyl disulfate; tetrahydrobisdemethoxydiferuloylmethane; tetrahydrodemethoxydiferuloylmethane; tetrahydrodiferuloylmethane; tococysteamide; totarol; hydroxydecyl ubiquinone; ubiquinone = coenz Q 10; carotenoids; lycopene.

5. Colloids according to one of claims 1 to 4, characterized in that the colloids are ZnO colloids.

6. Colloids according to one of claims 1 to 5, characterized in that they are ZnO colloids grafted with 3-hydroxybenzaldehyde.

7. Topical composition comprising colloids according to one of claims 1 to 6.

8. Topical composition for non-therapeutic use comprising colloids according to one of claims 1 to 6.

9. Topical composition according to claim 7 or 8, characterized in that it is free of hydrophilic and / or lipophilic, mineral and / or organic sun filters.

10. Topical composition according to one of claims 7 to 9, characterized in that 5 whether it is in aqueous, micellar or Pickering form.

11. Food supplement comprising colloids according to one of claims 1 to 6.

Images