Lipid nanoparticle composition containing Vitis vinifera extract, cosmetic use of lipid nanoparticle composition containing Vitis vinifera extract, antioxidant skin cosmetic product, and skin aging prevention and skin care method

Abstract

The present invention aims to solve the constant problems of the prior art related to the lack of stability of lipid nanoparticles containing Vitis vinifera extracts, and develops a composition of stable lipid nanoparticles containing Vitis vinifera extracts and the use of nanoencapsulated Vitis vinifera L. extracts as active substances in cosmetic compositions, especially anti-aging compositions. In particular, the present invention comprises less than 2.5% w / w of Vitis extract and an encapsulation system, which allows a better stabilization. The present invention is in the field of cosmetic preparations for treating the skin, especially relating to liposomal compositions containing plant extracts.

Description

[Technical field]

[0001] The present invention relates to a lipid nanoparticle composition comprising an extract of Vitis vinifera, nanoparticles, a cosmetic composition comprising said nanoparticles and their cosmetic use.The present invention is in the field of cosmetic preparations for skin treatment, and in particular to a solid lipid nanoparticle composition involving a plant extract. [Background technology]

[0002] Skin is the largest and most visible organ of the human body and stands out because it plays a fundamental role in maintaining life. Among the multiple functions it performs, they include protection against various mechanical injuries, parasitic and microbial invasion, chemicals and radiation. Under radiation, the skin routinely exerts protection against solar (UV) rays.

[0003] Another important role is protection against fluid loss and thermoregulation.

[0004] As a consequence of its physiological function, the skin is damaged daily by exogenous factors, which favor the appearance of several undesirable conditions, such as, for example, pigmentation disorders, wrinkles, dehydration, among other attacks on the skin, which are further favored by different intrinsic factors, mainly induced with ageing.

[0005] Thus, there is a continuing need to develop cosmetic compositions that beneficially alter, treat, inhibit, or help prevent such undesirable skin conditions.

[0006] Currently, various active ingredients, chemical or biological, have been proposed for the treatment of various skin disorders.These active substances are routinely added to cosmetic product bases for topical use.On the market, the most common cosmetic product forms are creams, gel creams, gels, ointments, serums and lotions, which can vary from aqueous compositions to anhydrous compositions, and include several types of emulsions (oil-in-water or water-in-oil).

[0007] The active ingredients selected for use in cosmetic product forms tend to have anti-inflammatory properties, photoprotective properties (UVA and UVB), antioxidant properties, moisturizing properties, whitening properties and anti-wrinkle properties. Some promote increased skin elasticity, while others improve the feel of the skin. It is always desirable for cosmetic product actives to have physical and chemical stability. It is also desirable for them to have satisfactory skin absorption and / or to have improved stability, bioavailability and skin permeability when incorporated into cosmetic product bases.

[0008] Concerning biologically active ingredients, grape extract (belonging to the genus Vitis, species Vitis vinifera) is an active substance recognized for its ability to act advantageously in the cosmetic treatment of undesirable skin conditions. This ability of Vitis vinifera extract is related to the large amount of phenolic compounds, among which anthocyanins stand out, in addition to flavonoids, procyanidins, catechins and phenolic acids such as gallic acid. In addition, Vitis vinifera extract also contains, in addition to resveratrol, glycosides from the flavonoids quercetin, kaempferol, myricetin and isorhamnetin, as well as the presence of coumaric acid, caffeic acid, ferulic acid and caftaric acid. Malvidin 3-O-glycoside is also a compound present in the extract.

[0009] Thus, the extract has several protective and cosmetic benefits against various conditions such as pigmentation disorders, wrinkles, dehydration, melasma, acne vulgaris, redness, among others.

[0010] However, the use of Vitis vinifera extracts in beauty product bases is limited by constant technical challenges related to their low stability, as they are extracts sensitive to different environmental conditions (light, oxygen, temperature). The low stability is intrinsically related to the ability of said extracts to perform beneficial biological functions on the skin. For example, resveratrol, an active ingredient usually present in Vitis vinifera extracts, is a highly photosensitive molecule that is converted from the trans (active) to the cis (inactive) isomer upon exposure to light.

[0011] Typically, instability is observed in Vitis vinifera extracts, either alone or in cosmetic product bases. The instability can be observed by changes in organoleptic properties (especially color) and physicochemical properties (pH and density).

[0012] A search of the prior art in the scientific and patent literature has revealed the following documents relevant to the subject matter of the present invention:

[0013] WO2011116963, published in 2011, teaches that solid lipid particles (SLN - solid lipid nanoparticles) exhibit improved chemical stability properties of the encapsulated species when the SLN are coated with a polymer. The stability described in this international application relates to greater protection of the encapsulated species against degradation due to interactions with other components of the composition, as well as other chemical protection such as against hydrolysis, oxidation and light.

[0014] In application WO 2011116963 a series of active substances to be encapsulated is presented, with Vitis vinifera extract being only one of several suggested plant extracts.

[0015] Thus, from the research literature, the lipid nanoparticles of Vitis vinifera extracts described in the prior art still present the problem of lack of stability of the extract, since this lack of stability is present both in lipid nanoparticle compositions containing Vitis vinifera alone or when formulated in a cosmetic product base. In the prior art, there is also no effective solution for improving skin penetration. Therefore, there is still a need to provide lipid nanoparticle compositions whose ingredients, among other advantages, solve the lack of stability when encapsulating Vitis vinifera extracts and in particular improve skin penetration, so that the composition becomes viable for its cosmetic purposes. [Prior art documents] [Patent documents]

[0016] [Patent Document 1] International Publication No. 2011116963 Brochure Summary of the Invention [Problem to be solved by the invention]

[0017] The present invention aims to solve the persistent problems of the prior art related to the lack of stability of compositions of lipid nanoparticles containing Vitis vinifera extracts through the development of a composition of improved stability and to enable the use of nanoencapsulated Vitis vinifera L. extracts as active substances in cosmetic compositions, in particular anti-ageing compositions. [Means for solving the problem]

[0018] In a first aspect, the present invention relates to a lipid nanoparticle composition comprising an extract of Vitis vinifera in an amount of about 0.1% to 2.0% by weight relative to the total weight of the composition, more specifically about 1% by weight of an extract of Vitis vinifera relative to the total weight of the composition.

[0019] In a second aspect, the present invention relates to the cosmetic use of the lipid nanoparticle composition of the first aspect as an antioxidant and anti-aging agent in the prevention of skin aging. Surprisingly, it has been found that the composition of the present invention is efficient in improving skin penetration and promoting a reduction in oxidative stress in the skin, exerting a protective effect against the excessive increase in synthesis of free radicals induced by exposure to UV radiation.

[0020] In a third aspect, the present invention relates to a dermocosmetic product for preventing skin aging, acting as an antioxidant and anti-aging agent, comprising at least a lipid nanoparticle composition of the first aspect and a cosmetically acceptable excipient.

[0021] In a fourth aspect, the present invention relates to a method of skin care comprising topically applying a layer of a product as defined in the third aspect.

[0022] Furthermore, the inventive concept common to the described and claimed protection contexts is that they all relate to a stable composition of Vitis vinifera extract lipid nanoparticles, which is surprisingly and unexpectedly improved over the prior art by (i) remaining a homogeneous system, (ii) preserving its organoleptic properties even under stress conditions, (iii) exhibiting a high encapsulation index, (iv) improving skin penetration, (v) exerting an anti-aging effect, and (vi) exerting an antioxidant effect and protecting the skin from the harmful effects of exposure to solar radiation.

[0023] These and other objects of the present invention are set forth in the following description in sufficient detail to enable those skilled in the art to readily understand and embody them. [Brief description of the drawings]

[0024] In order to better define and clarify the contents of this patent application, the following figures are presented:

[0025] [Figure 1]Figure 1 shows a comparison of stability profiles between three compositions of Vitis vinifera extract lipid nanoparticles that are virtually identical when subjected to oven stability testing (24 hours at 52 °C). Composition A contains 1% extract, composition A' contains 1.5% and composition A'' contains 2%. [Diagram 2] Three compositions of virtually identical Vitis vinifera extract lipid nanoparticles containing 2.5%, 5.0% and 10.0% extract are shown, demonstrating the infeasibility of the comparative compositions due to the formation of clusters and high viscosity that hinders the acquisition of nanoparticles. [Diagram 3] A calibration curve for total polyphenols showing an encapsulation efficiency of 99.97% is shown. [Figure 4] Fluorescence microscopy evaluation of skin penetration in cultures of human skin fragments incubated with the evaluated products. AC - untreated skin fragments (baseline control); D-F - skin fragments incubated with the evaluated products NVAC VITIS VINI (blank) + fluorescein; GI - 0.1% extract solution + fluorescein; J-L - NVAC VITIS VINI 10%; MO - NVAC VITIS VINI 10% + fluorescein. Fluorescein is marked in red. The reference bar corresponds to 20 μm. [Diagram 5] Figure 1 shows the evaluation of skin permeation in cultures of human skin fragments with the evaluated products NVAC VITIS VINI 10%, NVAC VITIS VINI 10% + fluorescein, NVAC VITIS VINI (blank) + fluorescein and extract solution 0.1% + fluorescein. Data represent the mean ± standard deviation of 12 replicates (ANOVA-Bonferroni). [Figure 6]Fluorescence microscopy evaluation of the synthesis of free radicals (FRs) in cultures of human skin fragments incubated with the evaluated product and exposed to ultraviolet (UV) radiation. In this figure, AC - untreated skin fragments (baseline control); D - F - skin fragments only exposed to UV radiation; GI - skin fragments incubated with the evaluated product NVAC VITIS VINI (blank) + fluorescein and subjected to UV radiation; J - L - skin fragments incubated with the evaluated product Extract Solution 0.1% + fluorescein and subjected to UV radiation; MO - skin fragments incubated with the evaluated product NVAC VITIS VINI 10% and subjected to UV radiation; PR - skin fragments incubated with the evaluated product NVAC VITIS VINI 10% + fluorescein and subjected to UV radiation; S - U - skin fragments incubated with the comparative commercial product VIT C 10% MOISTURIZING CREAM and subjected to UV radiation. FR is marked in green mainly on the dermis, blue markings represent cell nuclei (DNA; DAPI). The reference bar corresponds to 50 μm. [Figure 7] Semiquantitative results of FR labeling / generation obtained from analysis of microscopic images are presented. [Figure 8] FIG. 8 shows the size and surface charge of nanoparticles according to the present invention. [Figure 9] FIG. 9 shows the size and surface charge of nanoparticles according to the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0026] The present invention relates to a stable composition of lipid nanoparticles containing an extract of Vitis vinifera and the use of a composition containing nanoencapsulated Vitis vinifera L. as an active substance in a dermocosmetic composition, in particular an antioxidant anti-aging composition.

[0027] For the purposes of the present invention, unless otherwise specified, percentage values ​​refer to weight / weight percentages (% w / w), thus referring to the weight of one or more components relative to the total weight of the composition.

[0028] In the present invention, the term "lipid nanoparticles" can be understood as systems for releasing active substances, which are spherical with a diameter of 1 to 1000 nanometers and whose matrix is ​​formed by lipids. Lipid nanoparticles are systems that encapsulate at least a Vitis vinifera extract. Furthermore, in the present invention, nanoparticles containing a Vitis vinifera extract are inputs into cosmetic compositions, in particular due to their cosmetically active properties.

[0029] In the present invention, the term "Vitis vinifera extract" can also be understood as "Vitis extract" or "grape extract" and is defined as an extract of part (skin or seeds) or all of grapes. Vitis extract can be obtained by any method known in the prior art to extract grape constituents, preferably a method that preserves the quality and quantity of the components so that the extract can perform its cosmetic function.

[0030] In a particular embodiment, the Vitis vinifera extract of the present invention comprises gallic acid, catechin, epicatechin, procyanidin B1 and procyanidin B2.

[0031] By way of non-limiting example, the process for obtaining said extract may involve water as a solvent or a mixture of water and other solvents, such as alcohol. The process may include different unit operations for the industrial conversion of part (seeds or skins) or all of the grapes into an extract, such as crushing, solvent extraction, filtration, concentration, drying, sieving and packaging.

[0032] "Extract" means a fraction obtained from Vitis vinifera, which fraction may be enriched with respect to particular compounds, e.g., phenolic compounds, resulting in a fraction not achievable naturally without human intervention.

[0033] The composition of the present invention is for preparing lipid nanoparticles containing a Vitis vinifera extract, which is notable for having an improved stability effect compared to other lipid nanoparticles containing the same extract. The stability of the composition of the present invention is given by its ability to maintain its homogeneity, its organoleptic properties and its physicochemical properties even when exposed to the stress conditions foreseen in the stability tests.

[0034] The stability of the nanoparticle compositions of the present invention is directly related to their quality and chemical and physical integrity, as well as their useful life and feasibility in incorporating into other cosmetic product bases.

[0035] The lipid nanoparticle composition of the present invention is composed of a lipid phase, also called lipid matrix, which allows the encapsulation / retention of components. The lipid phase is formed by at least one lipid selected from a range of compounds such as, but not limited to, mono-, di- and triglycerides, fatty acids, sterols and waxes. The lipid phase may contain only solid lipids, only liquid lipids, or a mixture of solids and liquids. The lipid phase may be stabilized by the presence of at least one surfactant, or may have a polymer coating.

[0036] The nanoparticles of the present invention can be produced by different processes known in the prior art, such as ultra-homogenization and high-pressure homogenization (which may involve heating or cooling), as well as the solvent evaporation method, multiple emulsions or spontaneous emulsions. Preferably, the nanoparticles are produced by a high-pressure homogenization process.

[0037] If a polymer coating is desired, an additional coating step is performed by deposition or coupling of a polymer, which may be isolated or mixed, on the surface. This deposition can be performed using low-energy methods such as simple homogenization with a magnetic mixer and paddle, or high-energy methods such as high-pressure homogenizers, ultrasound or ultra-homogenizers. Furthermore, deposition can be performed immediately after obtaining the lipid nanoparticles in an uncoated state or after a long time during the process of obtaining the nanoparticles. The coupling of the polymer can be achieved by chemical reaction on the surface of the nanoparticles, by simple and short mixing, or by long incubation.

[0038] The lipid nanoparticles of the present invention encapsulate ingredients within the lipid matrix. The encapsulated ingredients are Vitis extract and cosmetic adjuvants. Adjuvants refer to any ingredient that can provide additional beneficial effects to the skin or the composition itself.

[0039] Adjuvants are substances that may or may not have a cosmetic effect. If the adjuvant has a cosmetic effect, it can be an emollient, a moisturizer, an antioxidant, a chemical or physical filter for sun protection, but is not limited to only these functional substances.

[0040] In other cases, the adjuvant is a substance that has a stabilizing effect, for example a preservative, an antioxidant, a chelating agent.

[0041] Surfactants and / or solvents can be used to solubilize and stabilize the encapsulated components within the lipid matrix and to make it possible to obtain nanoparticles by stabilizing the interface between the lipid and the aqueous phase.

[0042] The substances encapsulated by the lipid nanoparticles of the present invention can be lipophilic, hydrophilic or amphiphilic and, depending on the preparation process selected, can be incorporated into the lipid matrix by dissolving or dispersing in the lipid, by adsorption onto the surface of the lipid or by dispersing the active ingredient in the form of an aqueous solution in the lipid.

[0043] In the present invention, the lipid nanoparticles are found in the form of an aqueous dispersion, the nanoparticle composition having at least 50% by weight relative to the total weight of the water composition.

[0044] The presence of significant amounts of water in the composition may favor the formation of condensates in the formulated product, especially when the composition is exposed to high temperatures, whereas such condensates are expected and do not adversely affect the stability of the composition.

[0045] In a first aspect, the present invention relates to a lipid nanoparticle composition comprising an extract of Vitis vinifera in an amount of about 0.1-2.0% w / w based on the total weight of the composition.

[0046] Preferably, the amount of Vitis extract in the composition is about 0.5-1.5% w / w, more preferably, the amount of Vitis extract in the composition is about 1.0% w / w.

[0047] Less than 2% w / w Vitis extract is technically important, since when subjected to a stability test in an oven (52°C / 24 hours), compositions of lipid nanoparticles containing amounts of about 2.0% or more are shown to be unfeasible, as shown in Figure 1. Higher amounts of Vitis extract in the composition increase the likelihood of the formation of clusters, the occurrence of phase separation, a technical problem that implies obtaining a heterogeneous system that characterizes the lack of stability of the prepared composition. For example, at levels of 5% and 10%, the composition becomes unfeasible, forming a paste that makes solubilization and encapsulation impossible (Figure 2).

[0048] The amount of Vitis extract of the present invention is different from the prior art knowledge, which does not teach or suggest a specific amount of Vitis extract, and according to the prior art knowledge, one can think that any encapsulated amount would benefit from the stability effect, which is not observed in industrial practice (Figure 1 and Figure 2).

[0049] Surprisingly, the extract of the present invention formulated in an amount of about 0.1-2.0% by weight remains as a homogeneous system, demonstrating its good physical stability even when exposed to a temperature of 52° C. for 24 hours, and such effect is enhanced at amounts approaching 1.0%. In addition, a high encapsulation index is observed at amounts of about 0.1-2.0%.

[0050] Another surprising aspect observed in the present invention is the softness of the resulting colors, ranging from soft purple to peach.

[0051] In another embodiment of the first aspect, the present invention is formulated with about 0.1 to about 3% of a preservative. Preservatives suitable for the present invention are phenoxyethanol, caprylyl glycol, BHT, disodium EDTA, sodium metabisulfite, parabens, honeysuckle (Lonicera japonica), honeysuckle (Lonicera caprifolium), hydroxyacetophenone, 1,2-hexanediol, 1,2-octanediol, tropolone, pentylene glycol, sodium benzoate, potassium sorbate, iodopropynyl-butylcarbamate, imidazolidinyl urea, polyaminopropyl biguanide, or mixtures thereof. Preferably, the composition of the first aspect comprises at least 0.1 to 2% imidazolidinyl urea, 0.1 to 2% phenoxyethanol, 0.1 to 2% caprylyl glycol, or combinations thereof.

[0052] The selection of the preservative system is important for the present invention because it affects the improvement of the stability of the formulated product. The preservative prevents the change of the sensory and physicochemical properties, such as coloration, of the composition. In addition, the preservative inhibits microbiological growth. Providing an efficient preservative system compatible with Vitis extract is a challenge in the prior art.

[0053] In one embodiment of this aspect, the preservative system used acts to maintain the stability of the composition and control microorganisms, and the preservative system comprises at least imidazolidinyl urea, or a combination of phenoxyethanol and caprylyl glycol, both at a concentration of about 1.5% w / w, approximately 1:1. The efficiency of these preservative systems of the present invention is monitored, for example, by stability testing and microbiological control (challenge testing). Even more preferably, the preservative system used in the present invention comprises a combination of phenoxyethanol and caprylyl glycol, both at a concentration of about 1.5% w / w. The preservative system added to the Vitis extract in the form of lipid nanoparticles in an amount of less than about 2.0% confers stability to the Vitis extract and the nanoparticles of the present invention.

[0054] The composition of the present invention comprises about 10%-40% w / w lipid to form a lipid matrix. The lipid used to form the matrix may be lipid in liquid, semi-liquid, solid state or mixtures thereof at room temperature. Without being limited thereto, the lipid may be selected from simple or complex fatty acids, long, medium or short chain triglycerides.

[0055] Preferably, the present invention uses about 10%-30% medium chain triglycerides, fatty acids and polypropylene glycol stearyl esters. More preferably, the present invention uses 5%-10% capric / caprylic triglycerides, 5%-10% oleic acid, 1%-10% linoleic acid and 1%-5% PPG-15 stearyl ether.

[0056] The composition of the first embodiment comprises about 1% to 10% of a surfactant, which may be chosen from hydrophilic and lipophilic, ionic and non-ionic compounds or mixtures thereof.

[0057] Preferably, the composition uses 1-10% of an ethoxylated surfactant such as steareth (stearyl alcohol ethoxylate) and a non-ionic surfactant selected from poloxamer 407 (an oxirane-containing polymer).More preferably, the composition uses 1-5% steareth-2 (stearyl alcohol ethoxylate), 1-5% poloxamer 407 (an oxirane-containing polymer) and 0.1-2% steareth-21 (stearyl alcohol ethoxylate).

[0058] A first aspect of the present invention relates to a composition comprising at least the following components: more than 50% water, about 10-40% lipid, about 1-10% surfactant, about 0.1-3% adjuvant and about 0.1-2% Vitis extract, preferably 1% Vitis extract.

[0059] In the present invention, the composition may further optionally comprise a polymer for coating the nanoparticles. The composition may comprise 0.5% to 5% of a hydrophobic polymer and a hydrophilic polymer. The polymer may be selected from acrylic acid derived polymers, polylactic acid derived polymers, polymethacrylates, copolymers of ethylene and vinyl acetate, vinylpyrrolidone derived polymers, non-ionic block copolymers of ethylene oxide and propylene oxide, cellulose hydroxypropyl methyl ether polymers, hydroxyethyl cellulose, hydroxypropyl cellulose, ethyl cellulose, cellulose acetate phthalates (phthalic anhydride polymers and cellulose acetate esters), carboxymethyl cellulose, cellulose acetate (cellulose polymers partially acetylated to different degrees).

[0060] In a second aspect, the present invention relates to the cosmetic use of a lipid nanoparticle composition of the first aspect for preventing skin ageing by exerting antioxidant and anti-ageing effects.

[0061] The cosmetic use of the second aspect of the present invention derives from the fact that the lipid nanoparticle composition containing Vitis extract has antioxidant, anti-aging, anti-inflammatory, whitening, photoprotective and gene-regulating activity.

[0062] The above effects are achieved through improved performance with regard to skin penetration.

[0063] The antioxidant effect of the composition of the first aspect was determined by the DPPH (2,2-diphenyl-1-picrylhydrazyl), SOD effect (superoxide dismutase) and DCFH-Da (2,7-dichlorodihydrofluorescein-diacetate) methods. Using each method, it was observed that the composition (i) had antioxidant capacity 4 times greater than resveratrol, (ii) 12 times greater than vitamin C, (iii) 24 times greater than vitamin E, (iv) exhibited SOD effect on free radical scavenging, and (v) exhibited the ability to scavenge and remove free radicals in the intracellular environment.

[0064] The anti-aging effect of the composition of the first embodiment was determined by a method for measuring the activity of elastase enzyme and the activity of metalloprotease (MMP) enzyme. Using each method, it was observed that the composition has (i) the ability to inhibit the activity of elastase, which vitamins C and E do not exhibit, and (ii) the ability to inhibit the activity of three different types of MMP (1, 3, and 12), which vitamins C and E do not exhibit.

[0065] The anti-inflammatory effect of the composition of the first invention was determined by evaluating the activity of cyclooxygenase-2 (COX-2) enzyme. By using the above method, it was observed that the composition inhibits the expression of COX-2 enzyme.

[0066] The whitening effect of the composition of the first embodiment was determined by evaluating the activity of tyrosinase enzyme.By using this method, it was observed that the composition reduces the activity of tyrosinase enzyme and shows results comparable to market references such as kojic acid and arbutin.

[0067] The photoprotective effect of the composition of the first embodiment was determined by microscopic evaluation of the integrity of reconstructed human skin subjected to UV radiation.By using this method, it was observed that the composition can protect cells from damage caused by UVA and UVB radiation.

[0068] The gene regulation effect of the composition of the first aspect is determined through a panel that includes several genes.More specifically, the gene regulation effect is evaluated by mRNA expression profiling using RT-qPCR technology.Extracted mRNA is analyzed using PCR designed to analyze target genes selected for their importance in skin biology.By using this method, it is observed that the composition of the present invention can regulate genes related to skin aging.

[0069] The skin permeation enhancing effect and antioxidant effect were also demonstrated by preclinical evaluation of the skin permeation and antioxidant effect of the products evaluated in an ex vivo human skin experimental model.

[0070] In a third aspect, the present invention relates to a product for preventing skin aging, which product is intended to have an antioxidant and anti-aging effect, comprising a lipid nanoparticle composition according to the first aspect and a cosmetically acceptable excipient.

[0071] The product of the third aspect may contain ingredients with or without cosmetically active function. Among the ingredients with cosmetic function, any ingredient that is formulated for the preparation of dermatological products is highlighted, such as, in non-limiting examples, moisturizers, whitening agents, emollients, anti-wrinkle agents, anti-imperfection agents that increase the firmness and elasticity of the skin and give the skin a smooth feel to the touch. Among the ingredients without cosmetic function, any ingredient that is intended to enable the desired cosmetic product form, be it liquid, semi-solid or solid, is mentioned.

[0072] When in liquid form, the products of the present invention can be formulated as lotions and serums.

[0073] In the case of semi-solid or solid form, the products of the invention can be formulated as oil-in-water or water-in-oil emulsions, preferably in cream or gel-cream form.

[0074] Additionally, the product may be a gel preparation.

[0075] In a fourth aspect, the present invention relates to a method of skin care comprising applying to the skin a layer of a product as defined in the fourth aspect. EXAMPLES

[0076] The examples presented herein are intended to illustrate some of the many ways to practice the present invention, however, to help demonstrate the technical effects in a straightforward and comparative manner, and are not intended to limit the scope of the invention.

[0077] A direct way of demonstrating the technical effect is by demonstrating that composition A (invention) is stable in different stability tests, especially tests in which the composition is subjected to stress conditions. An indirect way is through comparative compositions B-J, which, although similar to the base composition, did not pass the stability tests under stress conditions due to differences in the amount of Vitis extract and / or preservative system.

[0078] Example 1 - Lipid Nanoparticle Composition A (Invention) [Table 1]

[0079] [Table 2]

[0080] Example 2 - Stability Comparison of Composition A Containing 1% Vitis vinifera Extract with Compositions A' (1.5%) and A'' (2%) Compositions A, A' and A" shown in Figure 1 refer to three different compositions that are identical in qualitative aspects and fairly similar in quantitative aspects, with only slight adjustments in the amount of Vitis extract used in each. Composition A is as shown in Table 1 and contains 1% Vitis extract, A' contains 1.5% and composition A" contains 2.0%.

[0081] The initial stability of each prototype was tested in an oven test (conditions: 54°C, 24 hours). Tables 3 and 4 show the observed variations in appearance of the three samples.

[0082] [Table 3]

[0083] [Table 4]

[0084] In conclusion, composition A (Table 1) was observed to be the most promising, mainly because it did not present any precipitate after completion of the stability test in an oven at 54 °C / 24 hours. The precipitate observed in the samples of compositions A' and A" was purple in color, characterizing that the concentration of Vitis vinifera extract in these compositions was higher than the concentration the system could support. However, the pH did not change significantly during the test. The pH variation was 4.04-4.17 for sample A, 3.72-3.49 for sample A', and 3.62-3.66 for sample A".

[0085] FIG. 1 shows aspects of three compositions (A, A' and A") before and after testing in a 54° C. oven / 24 hours.

[0086] Example 3 - Further stability testing of lipid nanoparticle composition A After the previous stability test in oven at 54° C. / 24 hours, a further set of tests was carried out to further investigate the stability of the lipid nanoparticle composition Composition A. The tests follow good practice for cosmetic stability testing and consider the parameters defined in Table 2 as indicators of stability.

[0087] Test 1: Centrifugation at 6000 rpm / 30 min The stability of composition A of the lipid nanoparticles of the present invention was evaluated by a centrifugation test at 6000 rpm / 30 min, referred to herein as test 1. The method used involved conditioning a sample of the nanoparticles in an eppendorf, followed by exposure of the container to rotation at a speed of 6000 rpm for 30 min at 25° C. At the end of the test, the integrity of the sample was evaluated with respect to suspension or phase separation.

[0088] After carrying out the test, no phase separation was observed in the composition and the composition remained homogeneous.

[0089] Therefore, samples containing lipid nanoparticle composition A were considered stable given the simulation of stress conditions that may result in phase separation.

[0090] Test 2: 54°C oven / 24 hours The stability of composition A of the lipid nanoparticles of the invention was again evaluated by a 54°C / 24h oven test, referred to herein as test 2. The method used involved exposing a sample of composition A to a temperature of 54°C for 24h, at the end of which the sample was evaluated for its organoleptic properties and physicochemical aspects. As mentioned above, the criteria considered in the evaluation were suspension separation, presence of oil on the surface, presence of condensation water, presence of clusters, presence of sediment, coagulation, color change, odor change, viscosity change. For physicochemical parameters, in addition to pH variation, density variation was also evaluated.

[0091] The results of Test 2 for samples of lipid nanoparticle composition A are shown in Tables 5 and 6.

[0092] [Table 5]

[0093] [Table 6]

[0094] Tables 5 and 6 make it possible to conclude that the sensory and physicochemical parameters evaluated are within the expected ranges.

[0095] Test 3: Preliminary stability test: Thermal shock The stability of composition A of the lipid nanoparticles of the invention was evaluated by a test of sudden changes in temperature (thermal shock), referred to herein as test 3. The method used involved subjecting the samples to 7 cycles of thermal stress, each cycle corresponding to a period of 24 hours at 5°C followed by 24 hours at 40°C. At the end of each cycle, the organoleptic properties and physicochemical aspects were evaluated. The criteria taken into account in the evaluation, again in this test, were suspension separation, presence of oil on the surface, presence of condensed water, presence of clusters, presence of sediment, color change, odor change, viscosity change, pH and density.

[0096] The results of Test 3 for samples of lipid nanoparticle composition A are shown in Tables 7, 8 and 9.

[0097] [Table 7]

[0098] [Table 8]

[0099] [Table 9]

[0100] In Tables 8 and 9, C1 to C7 refer to the respective thermal shock cycles in Test 3.

[0101] Tables 7 and 8 demonstrate that the parameters of density and pH are as expected even after several heat shock cycles. Table 9 shows that there was a shift in viscosity from the second cycle of heat shock. However, there was no significant change, and the product remained fluid and had good flow. The presence of condensed water was also observed, which is expected due to the presence of water in the composition. Other sensory parameters remained unchanged. Therefore, the sample containing lipid nanoparticle composition A is stable in terms of test 3.

[0102] Tests 4 and 5: Exposure to different temperatures and sunlight The stability of composition A of the lipid nanoparticles of the invention was evaluated in terms of different temperatures (Test 4) and exposure to sunlight (Test 5) to simulate other stress situations.

[0103] For this purpose, samples were exposed to temperatures of 5° C., 25° C. and 40° C. for a period of 90 days. The sensory and physicochemical aspects of the samples were evaluated at days 0, 1, 7, 15, 30, 60 and 90.

[0104] In addition, the stability of lipid nanoparticle composition A was evaluated under sunlight. For this purpose, samples were exposed to sunlight for 90 days. Sensory properties and physicochemical aspects of the samples were evaluated on days 0, 1, 7, 15, 30, 60 and 90.

[0105] For Test 4 and Test 5, the results relate to suspension separation, presence of oil on the surface, presence of condensed water, presence of clusters, presence of sediment, color change, odor change, viscosity change, pH and density analysis.

[0106] For Test 4, the formation of condensed water was observed in all conditions, which was an expected change due to the presence of water in the formulation. When the samples were kept at 40°C, a slight change in viscosity was observed, and the product became less viscous. Within 15 days at 40°C, subtle phase separation occurred. However, when the samples were shaken, they became homogenous again. After 30 days at 40°C, the samples showed a subtle color change and became paler. After 60 days at 5°C, the samples were found to be slightly more viscous. Since phase separation and viscosity changes were not significant, lipid nanoparticle composition A was considered stable in terms of Test 4.

[0107] For Test 5, both a small precipitate and a subtle color change occurred after 60 days of exposure to light. Although the sample is considered stable from the standpoint of Test 5, it is recommended not to expose this product to light.

[0108] Completing the exam Tests 1-5 clearly demonstrated that lipid nanoparticle composition A is stable and exhibits the expected variations in pH and density under the conditions to which composition A is exposed. There is only a slight color change in samples exposed to light, suggesting that embodiments of the present invention should be packaged in opaque packaging and protected from light.

[0109] Example 4 - "Load Test" Samples of lipid nanoparticle composition A were then tested by a challenge test aimed at evaluating the effectiveness of the preservative system (phenoxyethanol and caprylyl glycol, 1:1 ratio), which is necessary for satisfactory protection of the product against microbial contamination from manufacture until expiry date. The challenge consisted of intentionally contaminating the samples with specific microorganisms and evaluating their growth at defined time intervals up to 28 days. The microorganisms used in the challenge tests were Staphylococcus aureus (ATCC 6538), Pseudomonas aeruginosa (ATCC 9027), Escherichia coli (ATCC 8739), Aspergillus brasiliensis (ATCC 16404), and Candida albicans (ATCC 10231).

[0110] The test results are shown in Table 10.

[0111] [Table 10]

[0112] After completion of the test, the preservative system analyzed (phenoxyethanol and caprylyl glycol, 1:1 ratio) was observed to have antimicrobial efficacy as it met the test specifications.

[0113] Example 5 - Lipid Nanoparticle Composition B (Comparative) [Table 11]

[0114] Example 6 - Lipid Nanoparticle Composition C (Comparative) [Table 12]

[0115] Example 7 - Lipid nanoparticle composition D (comparative) [Table 13]

[0116] Example 8 – Comparison of the stability of nanoparticle compositions A-D [Table 14]

[0117] Example 9 - Stability of nanoparticle compositions E and F, E' and F' (comparative) Lipid nanoparticle compositions E and F, E' and F' were all prepared with 1% by weight of Vitis extract relative to the total weight of the composition and have similar ingredients in their compositions. The stability of the compositions was tested for 30 days at room temperature (no stress conditions).

[0118] Compositions E and F are prepared without a preservative system. Qualitative and quantitative details of these comparative compositions are provided in Table 15.

[0119] [Table 15]

[0120] Compositions E' and F' are prepared with a preservative system. Qualitative and quantitative details of these comparative compositions are provided in Table 16.

[0121] [Table 16] * It is commercially available as SymSave H®. ** It is commercially available as Sym Diol 68®.

[0122] After 30 days at room temperature (without stress conditions), compositions E' and F' containing 0.25% hydroxyacetophenone and 1,2-hexanediol + 0.25% caprylyl glycol as preservatives have a change in their organoleptic properties, emphasizing that the color has changed to brown. Therefore, compositions E' and F' are excluded, indicating that the selection of an inappropriate preservative system has a negative impact on the stability of the compositions.

[0123] After 30 days at room temperature (no stress conditions), compositions E and F were evaluated. Composition E remained purple. However, composition E showed (inhomogeneous) phase separation and was therefore excluded. Composition F showed promising results for the 30-day stability test (no stress conditions).

[0124] Therefore, composition F was selected for testing at a temperature of 45° C. In this test, this composition exhibited brown coloration and (inhomogeneous) phase separation.

[0125] The bases of compositions E, F, E' or F' were also tested for compositions with Vitis extract at concentrations of 2.5%, 5% and 10% relative to the total weight of the composition. On the other hand, even before the test, the compositions showed unsatisfactory results, given the formation of a paste with clusters (Figure 2).

[0126] The conclusion of this example is that only composition F containing 1% Vitis extract is stable and homogeneous within quality parameters when not exposed to stress conditions. However, under stress conditions (45°C), this composition did not show stability. To verify the effect of the preservative system on the stability of composition F, other molecules with antibacterial activity other than hydroxyacetophenone and 1,2-hexanediol 0.25% + caprylyl glycol 0.25% (composition F') were tested to produce compositions G, H, I and J.

[0127] Example 10 –Stability of lipid nanoparticle composition F in different preservative systems While keeping the basis of lipid nanoparticle composition F described in Example 9, different preservative systems were tested, resulting in compositions G, H, I and J. The results are shown in Table 17.

[0128] [Table 17]

[0129] Composition F + imidazolidinyl urea 0.5% preservative, Composition J, was stable in preliminary stability studies and is shown in Table 18.

[0130] [Table 18]

[0131] Composition J was then tested at room temperature and in an oven. This composition was deemed stable for 90 days of testing for both conditions tested. The average particle size was 186.6 nm. This formulation showed no tendency to instability and its encapsulation efficiency was 99.81%.

[0132] When subjected to a stress test, composition J also passed.

[0133] Composition J is also an embodiment of the present invention due to its ability to remain stable under the test conditions. This composition exhibited long term stability (greater than 90 days) when compared to composition A, but is presented as a comparative example since it exhibited less stability than composition A.

[0134] Example 11 – Encapsulation Efficacy Testing The composition according to the present invention was centrifuged at 6000 rpm for 3 hours at room temperature using a microtube with a filter (Ultrafree-MC Durapore Membrane PDVF 0.1 μm). The filtrate was collected and analyzed by UV / Vis spectrophotometry technique.

[0135] 15 mL of purified water, 1 mL of Folin-Ciocalteu reagent and 1 mL of standard solution or 1 mL of sample to be quantified were added to a test tube. Then 3 ml of sodium carbonate 12.5% ​​were added. The solution was homogenized and placed in a water bath at 55° C. for 15 minutes. After this time, the samples were cooled and their absorbance was measured at a wavelength of 755 nm.

[0136] From the concentrations of the standard solutions and the final volumes of the solutions analyzed, the concentrations of gallic acid at each point of the calibration curve were recalculated in increasing order of 0.00025 mg / mL; 0.0005 mg / ml; 0.0025 mg / ml; 0.005 mg / ml; 0.0075 mg / ml and 0.0125 mg / ml.

[0137] After reading the absorbance for each concentration, a calibration curve was created for gallic acid. The coefficient of determination (r 2 ) was 0.9995. The resulting curve and equation are shown in the graph of FIG.

[0138] The absorbance values ​​of the solutions containing the samples were read and the concentrations of polyphenols expressed as gallic acid were calculated using the equation of the line.

[0139] After processing the data, the concentration of the total unencapsulated polyphenols expressed as gallic acid was found to be 0.002603 mg / mL. The composition tested has 1% active dried grape skin extract and, according to the analysis carried out, the concentration of total polyphenols in the dried grape skin extract is 99.8%.

[0140] In this sense, the composition according to the invention has a total polyphenol concentration of 9.98 mg / ml. The encapsulation efficiency was 99.97%.

[0141] Example 9 - Preclinical evaluation of skin permeation and antioxidant efficacy of products evaluated in an ex vivo human skin experimental model Skin permeation: Xenobiotics, including drugs, cosmetic product ingredients, pesticides and other products, can be absorbed through human skin and thus come into contact with the skin tissue layer or become systemically available. The consequences of this event include beneficial effects from drugs and cosmetic product ingredients that are applied topically to the skin, as well as harmful effects from compounds to which the skin is exposed (e.g., occupational exposure). Therefore, determining the absorption of individual compounds through human skin is of utmost importance for accurate prediction of benefits and risks.

[0142] Assessment of antioxidant activity: A very common event after exposure to UV radiation is the formation of free radicals such as superoxide and hydroxyl radicals by the process of oxidative phosphorylation, which cause damage to cellular components, namely lipids and proteins, and especially to nucleic acids. The balance between the production of FRs and the innate antioxidant defenses is essential for the maintenance of physiological homeostasis. When FRs overload the body's ability to neutralize them, a condition known as oxidative stress begins, increasing the susceptibility of skin tissues to diseases that are quickly manifested in aesthetic changes resulting from the formation of radical proteins.

[0143] Understanding the balance between the production and neutralization of free radicals has prompted the development of research on oxidative damage markers using chemical or biological systems to evaluate the effectiveness of antioxidants. Among the models used is the measurement of the fluorescence intensity emitted by the oxidation of the dichloro-dihydro-fluorescein diacetate probe (DCFH-DA) in 2'-7' dichlorofluorescein (DCF).

[0144] This technique allows the evaluation of the antioxidant effect of the formulation against the exogenous factors to which our skin is constantly exposed. Therefore, the early neutralization and / or inhibition of FRs can prevent the signaling cascades or chemical reactions that inevitably accelerate aging.

[0145] The samples analyzed were as follows: - NVAC VITIS VINI (10% concentration of nanoparticles of the present invention) - NVAC VITIS VINI 10% + Fluorescein - NVAC VITIS VINI (blank) + Fluorescein - Extract solution 0.1% + fluorescein

[0146] Human skin fragments obtained from elective plastic surgery were treated for 8 hours with the evaluated products NVAC VITIS VINI 10%, NVAC VITIS VINI 10% + fluorescein, NVAC VITIS VINI (blank) + fluorescein and extract solution 0.1% + fluorescein for the evaluation of subsequent skin penetration. Additionally, the fragments were treated for 48 hours with the evaluated products and market comparison product (benchmark) VIT C 10% MOISTURIZING CREAM for further exposure to UV light and evaluation of free radical synthesis using the fluorescent probe DCFH-DA (dichloro-dihydro-fluorescein diacetate).

[0147] The skin fragments used in this study were derived from three healthy individuals, female, phototype (skin type) III, aged 29, 32 and 38 years, who underwent elective plastic surgery (abdominoplasty) in the abdominal area. After the surgical procedure, the skin fragments were collected in plastic bottles containing 0.9% saline and kept under refrigeration for up to 24 hours. This project did not involve the storage of biological material for future use and the spare fragments were properly disposed of as infectious waste. The use of human skin fragments from elective surgery to carry out this study was in accordance with the Research Ethics Committee of Universidade Sao Francisco-SP under opinion 2,493,285 (Annex III), CAAE 82685618.9.0000.5514.

[0148] Cut the skin fragment into pieces of approximately 1.5 cm 2The cells were fractionated into fragments, placed in culture plates (Corning, USA) containing DMEM culture medium containing 10% fetal bovine serum (FBS) and 0.1% gentamicin, and maintained in an incubator at 37°C in the presence of 5% CO2.

[0149] To evaluate skin penetration, skin fragments were treated with 15 mg of the evaluated products NVAC VITIS VINI 10%, NVAC VITIS VINI 10% + fluorescein, NVAC VITIS VINI (blank) + fluorescein and extract solution 0.1% + fluorescein for 8 hours. The fragments were then collected and submitted to tissue sections for further analysis under fluorescence microscopy (Olympus, Japan - BX53) using CellSens software ((Copyright) 2010 OLYMPUS CORPORATION). Fluorescence intensity parameters emitted by fluorescein were evaluated. After obtaining images, the fluorescence intensity was quantified using ImageJ software (version 1.48, arbitrary units - AU).

[0150] For comparative evaluation of antioxidant activity, skin fragments were treated with 15 mg of the evaluated products and the market comparison product (benchmark) VIT C 10% MOISTURIZING CREAM. After 48 h of incubation, the skin specimens were irradiated with 10 J / cm using a UVA Cube 400, SOL 500 H1 filter and UV Meter (Honle UV America Inc., MA, USA) device. 2 The cultures were incubated with the evaluated products for an additional 24 hours and fragments were collected for labeling and semi-quantification of free radical synthesis using the DCFH-DA probe.

[0151] After the treatment period, skin fragments were embedded in Tissue-Tek® OCT™ and serial 12 micrometer tissue sections were then collected directly onto cryostat silanized slides (Leica, Germany - CRYOCUT 1800).

[0152] The sections were then washed with phosphate buffered saline (PBS) and incubated with a solution of dichloro-dihydro-fluorescein diacetate (DCFH-DA; Sigma, USA) (1:10,000 in phosphate buffer) for 1 min.

[0153] Immediately after this incubation, the slides were mounted using a specific mounting medium and analyzed under a microscope (Olympus, Japan - BX53) using CellSens software ((Copyright) 2010 Olympus). The fluorescence intensity parameters emitted by the oxidation of the DCFH-DA probe were evaluated. After obtaining images, the fluorescence intensity was quantified using ImageJ software (version 1.48, arbitrary units - AU).

[0154] To evaluate the semi-quantitative skin permeation and free radical synthesis using DCFH-DA, ANOVA test is used, which also allows the measurement of the variation of results by comparing the data between groups.Then, Bonferroni post-hoc test is applied, which strengthens the results presented in ANOVA test and makes them even more accurate.A significance level of 5% is used in both evaluations (GraphPad Prism v6).

[0155] Figure 4 shows the results obtained from the skin permeation of the evaluated products NVAC VITIS VINI (blank) + fluorescein; extract solution 0.1% + fluorescein; NVAC VITIS VINI 10% and NVAC VITIS VINI 10% + fluorescein in human skin cultures. As can be seen, the positive test control - NVAC VITIS VINI (blank) + fluorescein, as well as the evaluated products extract solution 0.1% + fluorescein and NVAC VITIS VINI 10% + fluorescein, showed an increase in fluorescence intensity compared to the baseline control. As expected, the evaluated product NVAC VITIS VINI 10% showed a low fluorescence intensity, similar to the baseline control.

[0156] Complementarily, Figure 5 shows the semi-quantitative results of fluorescence obtained from the analysis of the microscopic images. As can be seen, treatment with the evaluated products NVAC VITIS VINI (blank) + fluorescein; extract solution 0.1% + fluorescein and NVAC VITIS VINI 10% + fluorescein promoted an increase in fluorescence intensity (dermis + epidermis) of 21.19-fold, 11.79-fold and 17.70-fold, respectively, compared to the baseline control (P<0.001). It was also observed that the fluorescence intensity observed for the sections treated with extract solution 0.1% + fluorescein and NVAC VITS VINI 10% + fluorescein was considered statistically different (P<0.001) with respect to the sections treated with the evaluated product NVAC VITS VINI (blank) + fluorescein.

[0157] In addition, skin sections treated with the evaluated product NVAC VITIS VINI 10% + fluorescein showed higher fluorescence intensity (P<0.05) mainly in the viable epidermal area and dermis than sections treated with extract solution 0.1% + fluorescein (Figure 1 - G-I and M-O). In this sense, these results suggest that the encapsulated product showed a more pronounced skin penetration compared to the product in its free form.

[0158] Figure 6 shows the antioxidant effect of the evaluated products NVAC VITS VINI (blank) + fluorescein, extract solution 0.1% + fluorescein, NVAC VITS VINI 10% and NVAC VITS VINI 10% + fluorescein in human skin cultures subjected to UV radiation. As expected, radiation exposure led to an increase of 187.60% (P<0.001) in FR labeling / production compared to unexposed controls, thus contributing to the process of oxidative stress installation.

[0159] The evaluated product NVAC VITIS VINI (blank) + fluorescein, as expected, did not show a protective effect in preventing the formation of FRs when compared to the UV group, whereas the evaluated products Extract Solution 0.1% + fluorescein, NVAC VITIS VINI 10% and NVAC VITIS VINI 10% + fluorescein demonstrated a protective effect in preventing the formation of FRs.

[0160] Complementarily, in Figure 7, semi-quantitative results of FR labeling / production obtained from the analysis of microscopic images are shown. As can be seen, treatment with the evaluated products extract solution 0.1% + fluorescein, NVAC VITIS VINI 10% and NVAC VITIS VINI 10% + fluorescein promoted a 50.47%, 42.39% and 56.30% decrease in FR production, respectively, compared to the UV group (P<0.001).

[0161] Similarly, the market comparator product VIT C 10% MOISTURIZING CREAM promoted a 52.27% decrease in FR synthesis, also compared with the UV group (P<0.001).

[0162] The skin permeation results showed that the evaluated product NVAC VITIS VINI 10% + Fluorescein exhibited improved skin permeation compared to the product Extract Solution 0.1% + Fluorescein. In addition, the evaluated products Extract Solution 0.1% + Fluorescein, NVAC VITIS VINI 10% and NVAC VITIS VINI 10% + Fluorescein promoted a reduction in oxidative stress in the skin and exerted a protective effect against the excessive increase in the synthesis of free radicals induced by exposure to UV radiation. Similarly, the market comparison product VIT C 10% MOISTURIZING CREAM also promoted a reduction in the production of free radicals after exposure to UV radiation. Thus, these results reveal that the evaluated products exert antioxidant and anti-aging effects and protect the skin from the harmful effects of exposure to solar radiation.

[0163] Example 10 - Characterization - Results of using the Nano Zetasizer to evaluate size In analysis using a Nano Zetasizer for size assessment, the particles were observed to have a mean diameter of 362 nm, a monodisperse size distribution and an average surface charge of -30.9 mV. This result is considered to be within the scope of the present invention. The size and surface charge can be seen in Figures 8 and 9, respectively.

[0164] Example 11 –Gene Regulation Assays Within the scope of the present invention, the effect of gene modulation was determined by using a panel containing several genes. The effect of multiple UV radiations (UVA-6J / cm2) on gene expression profile in a full-thickness reconstructed skin model was evaluated. 2 (+UVB-310mJ / cm 2 ) × 4 days) upregulation and downregulation effects were observed.

[0165] Downregulation was observed in genes involved in extracellular matrix synthesis (COL1A1, COL3A1, ELN, FN1, FBN1), genes involved in cellular and oxidative stress responses (SEMA3A), genes involved in DNA repair (PCNA), genes involved in keratinocyte differentiation (CALML5, CASP14, FLG, KRT10, LOR, KRT1), genes involved in hydration (AQP3), genes involved in cell-cell junctions (DSC1, DSG1) and genes involved in desquamation (KLK7).

[0166] Upregulation was observed in genes involved in growth factors (NGF, EGF, FGF2), extracellular matrix degradation (MMP1, MMP3, PTGS2, TFPI2), cellular and oxidative stress response / inflammation (FOXO3, HMOX1, MT1E, MT1H, TXNRD1), DNA repair (XPA, ERCC3), keratinocyte differentiation (IVL, TGM1, TCHH), innate immunity (DEFB4A), keratinocyte proliferation (KRT19), and inflammation (IL1B, IL8).

[0167] The compositions of the present invention were also able to regulate genes associated with skin aging.

[0168] Those skilled in the art will be able, by utilizing the knowledge presented herein, to reproduce the invention in the presented embodiments and other variations that are covered by the scope of the appended claims.

Claims

1. A composition of lipid nanoparticles containing Vitis vinifera extract, comprising 0.1 to 2.0% by weight of Vitis vinifera extract based on the total weight of the composition, wherein the physical boundary of the nanoparticles is a lipid matrix.

2. The composition according to claim 1, comprising 0.5 to 1.5% by weight of Vitis vinifera extract based on the total weight of the composition.

3. The composition according to claim 2, comprising 1.0% by weight of Vitis vinifera extract based on the total weight of the composition.

4. The composition according to claim 1, wherein the Vitis vinifera extract comprises gallic acid, catechin, epicatechin, procyanidin B1 and procyanidin B2.

5. The composition according to claim 1, comprising 0.1 to 3% by weight of a preservative.

6. The preservative is selected from the group consisting of phenoxyethanol, caprylyl glycol, BHT, disodium EDTA, sodium metabisulfite, parabens, honeysuckle, honeysuckle, hydroxyacetophenone, 1,2 - hexanediol, 1,2 - octanediol, tropolone, pentylene glycol, sodium benzoate, potassium sorbate, iodopropynyl - butylcarbamate, imidazolidinyl urea, polyaminopropyl biguanide, or mixtures thereof. The composition according to claim 5.

7. The composition according to claim 1, comprising 0.1 to 2% of phenoxyethanol and 0.1 to 2% of caprylyl glycol.

8. The composition according to claim 7, wherein the preservative comprises a 1:1 combination of phenoxyethanol and caprylyl glycol.

9. The composition according to claim 1, comprising 10 to 40% w / w of lipid.

10. The composition according to claim 9, comprising 10 to 40% by weight of lipid based on the total weight of the composition, wherein the lipid is selected from simple or complex fatty acids, long - chain, medium - chain or short - chain triglycerides, polypropylene glycol stearyl ester or mixtures thereof.

11. The composition according to claim 10, characterized by containing 5% to 10% capric / caprylic triglyceride, 5% to 10% oleic acid, 1% to 10% linoleic acid, and 1% to 5% PPG-15 stearyl ether.

12. The composition according to claim 1, characterized by containing a surfactant selected from 1% to 10% of an ethoxylated nonionic surfactant such as stearyl alcohol ethoxylate, poloxamer, or a mixture thereof.

13. The composition according to claim 12, characterized by containing 1% to 5% of Steres-2 (stearyl alcohol ethoxylate), 1% to 5% of poloxamer 407 (a polymer having oxirane), and 0.1% to 2% of Steres-21 (stearyl alcohol ethoxylate).

14. The composition according to claim 1, characterized by having a soft purple to soft peach color.

15. The composition according to claim 1, characterized in that the particles have an average diameter of 300 to 420 nm.

16. The composition according to claim 15, characterized in that the particles have an average diameter of 360 nm.

17. The composition according to claim 1, characterized in that the particles have an average surface charge of -10 to -50 mV.

18. The composition according to claim 17, characterized in that the particles have an average surface charge of -30 mV.

19. The cosmetic use of a composition of lipid nanoparticles containing the Vitis vinifera extract according to any one of claims 1 to 18, for the preparation of a cosmetic product for preventing skin aging, which has an antioxidant effect, an anti-aging effect, an anti-inflammatory effect, a whitening effect, a light protection effect, a skin permeation effect, and a gene regulation effect related to skin aging.

20. Downregulation of genes involved in extracellular matrix synthesis (COL1A1, COL3A1, ELN, FN1, FBN1), genes involved in cellular stress response and oxidative stress response (SEMA3A), genes involved in DNA repair (PCNA), genes involved in keratinocyte differentiation (CALML5, CASP14, FLG, KRT10, LOR, KRT1), genes involved in hydration (AQP3), genes involved in cell-cell adhesion junctions (DSC1, DSG1) and genes involved in desquamation (KLK7), and upregulation of genes involved in growth factors (NGF, EGF, FGF2), genes involved in extracellular matrix degradation (MMP1, MMP3, PTGS2, TFPI2), genes involved in cellular stress response and oxidative stress response / inflammation (FOXO3, HMOX1, MT1E, MT1H, TXNRD1), genes involved in DNA repair (XPA, ERCC3), genes involved in keratinocyte differentiation (IVL, TGM1, TCHH), genes involved in innate immunity (DEFB4A), genes involved in keratinocyte proliferation (KRT19), genes involved in inflammation (IL1B, IL8), the use according to claim 19.

21. An antioxidant skin beauty product for preventing skin aging, comprising at least one composition of lipid nanoparticles according to any one of claims 1 to 18 and a cosmetically suitable excipient.

22. The product according to claim 21, characterized in that it is liquid, semi-solid or solid.

23. The product according to claim 22, characterized in that it is a lotion or serum.

24. The product according to claim 23, characterized in that it is an oil-in-water or water-in-oil emulsion.

25. The product according to claim 24, characterized in that it is used in the preparation of a cream or a gel cream.

26. The product according to claim 25, characterized in that it is for use in the preparation of a gel.

27. A skin care method, comprising the step of providing at least one layer of the product according to claim 21 to the skin in need thereof.

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