Multilayer-based cosmetic products, method of production and use thereof

Abstract

The present invention falls within the area of polymeric materials based on ultrafine fibres applied to the cosmetics and pharmaceutical sector, the latter relating to the method and application thereof for the production of solid products with high cosmetic efficiency in multilayer format manufactured by electro-hydrodynamic, aero-hydrodynamic processing techniques or any combination of the two.

Description

[0001] DESCRIPTION

[0002] Multi-layered cosmetic products, their preparation procedure and use

[0003] TECHNICAL SECTOR

[0004] The present invention falls within the area of ​​polymeric materials based on ultra-fine fibers applied to the cosmetic sector, referring to its process and application for manufacturing solid products of high cosmetic efficiency in multi-layer format manufactured using electro-hydrodynamic, aero-hydrodynamic processing techniques or any combination of both.

[0005] BACKGROUND OF THE INVENTION

[0006] Cosmetic ingredients, also known as bioactive compounds, are compounds that include biomolecules, enzymes, liposomes, anti-inflammatory agents, probiotics, prebiotics, symbiotics, antioxidants, cell regenerators, anti-wrinkle agents, anti-shine agents, etc.

[0007] Conventional cream formulations face challenges when combining various ingredients to achieve a stable, effective, and safe composition. These challenges include ingredient compatibility, proper emulsification, preservation, stability, texture, appearance, bioactivity of active ingredients, skin penetration and absorption, allergens and irritation, and regulatory compliance. The use of solid creams in the form of micron- or submicron-sized fibers can overcome several of these problems.

[0008] The formation of ultrafine fibers prepared by electro-hydrodynamic or aero-hydrodynamic processing, e.g., electrospinning, also known as electro-spinning, allows the design of products for, for example, the immediate and deep absorption of cosmetic bioactives through the skin or to absorb skin oil more efficiently. In the electrospinning technique, the effect of voltage on the solution causes the solvent to evaporate rapidly, causing the fibers to form immediately and act as a cosmetic ingredient per se and / or efficiently trap the cosmetic ingredient in the fibers. In the latter case, the result is optimal encapsulation of the cosmetic ingredient within the fiber structure, as well as a reduction in the ability of its molecules to crystallize, thus maintaining an amorphous or quasi-morphous state, which facilitates its dissolution, diffusion, and adsorption.The micro / nano structure of these materials provides a higher surface area / volume ratio and improved mechanical properties compared to other techniques for generating, for example, cosmetic films that disappear into the skin. Furthermore, it allows for the preparation of cosmetic formulations in a solid state, without water or oils, and potentially without any preservatives or other stabilizing or emulsifying additives. By generating solid creams, the water activity is also very low, eliminating the need for time-consuming testing to ensure the absence of microbiological contamination. These techniques increase the sustainability of the cosmetic product by reducing weight and volume and also simplifying packaging.However, polymers and active compounds may be partially retained on the substrates and therefore not be optimally and completely released onto the skin, require separate encapsulation in cosmetic formulations and / or create their bioactive or more bioactive form in situ during application to the skin.

[0009] The present invention aims to solve the difficulties previously raised by formulating multilayers based on fibers processed by electro-hydrodynamic or aero-hydrodynamic techniques for their advantageous cosmetic use.

[0010] DESCRIPTION OF THE INVENTION

[0011] The present invention proposes a multi-layered cosmetic product (e.g., for making cosmetic patches or masks), configured for application to the skin, capable of completely releasing bioactive agents and / or creating in-situ bioactive agents beneficial to the skin. The cosmetic product is manufactured primarily using electrohydrodynamic, aerohydrodynamic, or any combination of processing techniques. The products can be manufactured monoaxial, coaxial, by co-deposition, or layer-by-layer, and contain one or more bioactive agents and / or bioactive agent precursors encapsulated therein. Each layer is composed of micrometric and / or submicrometric fibers.The bioactive agent or its precursors are encapsulated using solutions, dispersions, or emulsions of the polymers and the bioactive agents or their precursors, which will form a solid product made of ultra-fine fibers that facilitate homogeneous and controlled release and / or the instant creation of bioactive agents on the skin.

[0012] Generally, the products of the invention are composed of between two and three layers of fibers based on water-soluble polymers, which are supported by a substrate or support layer made of electrospun fibers of any known polymer or combination of polymers, or of any woven or nonwoven material (also called TNT or nonwoven). The support layer can also be a continuous film, which can be transparent, colored or opaque, as well as a perforated film (see Figure 1).

[0013] A first aspect of the present invention relates to a self-adhesive cosmetic product that optimally and completely contains and releases bioactive agents and / or precursors of bioactive agents on moistened skin, said product comprising or consisting of:

[0014] - a layer of polymeric fibers (A) being the layer that comes into contact with the skin, said layer comprising at least one encapsulated bioactive agent and / or a precursor of a bioactive agent, the fibers having an average diameter size between 50 nm and 5 nm, more preferably between 100 nm and 3 nm, and even more preferably between 200 nm and 1 nm, measured by scanning electron microscopy (SEM); preferably the layer of fibers has a surface density of at least 0.01 g / m 2 , more preferably between 0.1 and 300 g / m 2 , and even more preferably between 0.1 and 50 g / m 2and where the polymeric fibers are made up of at least one water-soluble polymer selected from proteins or polysaccharides, as well as any mixture of the above.

[0015] - and a sacrificial layer (B) of polymeric fibers arranged immediately above the layer (A), said layer optionally comprising at least one encapsulated bioactive agent and / or a precursor of a bioactive agent, the fibers having an average diameter size between 50 nm and 5 nm, more preferably between 100 nm and 3 | im , and even more preferably between 200 nm and 1 | m, measured by scanning electron microscopy (SEM); the fiber layer preferably has a surface density of at least 0.01 g / m 2 , more preferably between 0.1 and 300 g / m 2 , and even more preferably between 0.1 and 50 g / m 2and where the polymeric fibers are made up of at least one water-soluble polymer selected from proteins or polysaccharides, as well as any mixture of the above. This layer (B) is called sacrificial, since most of it is not absorbed into the skin during application, but ensures that the bioactive agents and / or precursors of the bioactive agents present in layer (A) are released in the most optimal and complete way onto the skin; and

[0016] - a support or substrate layer (S), characterized in that the substrate comprises a material that is insoluble in water or has a lower solubility than layers B and A, on which the polymer fiber layers (B) and (A) are located, thus forming an ABS structure from the skin outwards. This substrate layer (S) must preferably have a surface density of at least 0.1 g / m 2 ; more preferably between 1 and 10,000 g / m 2; and even more preferably between 1 and 500 g / m 2 .

[0017] The characteristics and specific composition of this cosmetic product allow it to adhere and dissolve quickly on moistened skin, providing an inherent cosmetic firming, soothing / anti-irritation, anti-wrinkle and moisturizing effect, which will be reinforced or complemented by bioactive agents and / or precursors of encapsulated bioactive agents that are released and / or generate bioactive agents on the skin to generate together and optimally an enhanced anti-wrinkle, firming, soothing / anti-irritation, antibacterial, cleansing, nourishing, decongestant, antioxidant, depigmenting, regenerating, rejuvenating / anti-aging, moisturizing, emollient, illuminating, sebum-regulating, etc. effect.Additionally, because it is made of very fine fibers, the high surface area / volume ratio of these fibers generates a homogeneous application on the skin, mimicking its topology and thus facilitating its application, the immediate release and / or creation of bioactive agents, improving their adsorption on the skin and, therefore, their effectiveness. Furthermore, by having a sacrificial layer, we ensure that the bioactive agents and / or precursors of the bioactive agents incorporated into the cosmetic product are deposited mostly or completely on the skin.

[0018] In a preferred embodiment, the product of the invention comprises a layer of polymeric fibers (A') between layers (A) and (B), wherein said layer comprises at least one bioactive agent and / or a precursor of the encapsulated bioactive agent, the fibers having an average diameter size between 50 nm and 5 nm, more preferably between 100 nm and 3 nm, and even more preferably between 200 nm and 1 nm, measured by scanning electron microscopy (SEM); the layer of fibers preferably has a surface density of at least 0.01 g / m 2 , more preferably between 0.1 and 300 g / m 2 , and even more preferably between 0.1 and 50 g / m 2 and where the polymeric fibers are made up of at least one water-soluble polymer selected from proteins or polysaccharides, as well as any mixture of the above.

[0019] According to the present invention, "fiber" refers to elongated elements whose length is greater than their width (diameter). The average diameter of the fibers described in the present invention is measured by scanning electron microscopy (SEM).

[0020] The polysaccharides that make up the polymeric fibers of any of the layers (A), (A') or (B) can be selected independently of each layer, without limitation, from: modified pectin, alginic acid, hyaluronic acid, agar-agar, agaropectin, alpha cellulose, alpha glucan, amylopectin, amylose, beta glucan, callose, carrageenan, cellulose, oxidized cellulose, dextran, dextin, ficoll, fructosan, fucoidan, galactogen, galactomannan, glycosoaminoglycan, glucan, glycogen, glucomannan, gum arabic, cassia gum, sterculia gum, gellan gum, guar gum, karaya gum, tragacanth gum, cashew gum, xanthan gum, hemicellulose, kefiran, lentinan, levan polysaccharide, lipopolysaccharide, maltodextrin, pectin, polydextrose, pullulan, keratan sulfate, chitin, chitosan, sinistrin, xanthan, xylan, xyloglucan, fructans, microbial polysaccharides such as and without limitation fucopol (fucose-rich polyanionic polysaccharide), as well as any mixture of the above.

[0021] The proteins that make up the polymeric fibers of any of the layers (A), (A') or (B) can be selected independently of each layer, but not limited to, from: collagen, gelatin, zein, amaranth protein, hemp protein, keratin and its hydrolyzate, whey protein and its hydrolyzate, pea protein and its hydrolyzate, wheat protein and its hydrolyzate, soy protein and its hydrolyzate, elastin or any combination thereof.In a preferred embodiment, the polymeric fibers, of layers (A), (B) or (A') independently each one, in addition to the water-soluble polymer selected from proteins, polysaccharides, or any mixture thereof, are formed by a polymer selected from PEG (polyethylene glycol) (also called PEO (polyethylene oxide), hereinafter referred to as PEG to any PEG polymer (low molecular weight liquids) or PEO (high molecular weight solids)), polyglyceryl-4-caprate, natural deep eutectic solvents (NADES) and any combination thereof.

[0022] In a preferred embodiment, the NADEs will be selected without limitation from: lactic acid:sucrose, lactic acid:sucrose:water, citric acid:propylene glycol, fructose:glucose:sucrose:water, choline chloride:urea:water and any combination thereof.

[0023] In a preferred embodiment, the polymeric fibers of layers (A), (B) or (A'), each independently, are composed of pullulan, fructan, fucopol, cashew gum, elastin, collagen, as well as any mixture of the foregoing. More preferably, these fibers may also be composed of other polymers selected from PEG, NADES, polyglyceryl-4-caprate, and any combination thereof.

[0024] In a more preferred embodiment, the polymeric fibers of layers (A), (B), or (A'), each independently, are composed of at least pullulan. More preferably, pullulan or pullulan and elastin.

[0025] In a preferred embodiment, the polymeric fibers, of layers (A), (B) or (A') independently each one, are formed by a pullulan / elastin mixture where the percentage by weight of elastin in the polymeric composition is less than 10%, the rest would correspond to pullulan (up to 100% by weight of the polymeric mixture).

[0026] In another preferred embodiment, the polymeric fibers of layers (A), (B) or (A'), each independently, are formed by a pullulan / PEG mixture where the percentage by weight of PEG in the polymeric composition is less than 30%, the remainder would correspond to pullulan (up to 100% by weight of the polymeric mixture). In another preferred embodiment, the polymeric fibers of layers (A), (B) or (A'), each independently, are formed by a pullulan / polyglyceryl-4-caprate mixture where the percentage by weight of polyglyceryl-4-caprate in the polymeric composition is less than 6%, the remainder would correspond to pullulan (up to 100% by weight of the polymeric mixture).

[0027] In another preferred embodiment, the polymeric fibers, of layers (A), (B) or (A') independently each one, are formed by a pullulan / collagen mixture where the percentage by weight of collagen in the polymeric composition is less than 50%, the rest would correspond to pullulan (up to 100% by weight of the polymeric mixture).

[0028] In another preferred embodiment, the polymeric fibers, of layers (A), (B) or (A') independently each one, are formed by a pullulan / collagen / polyglyceryl-4-caprate mixture where the percentage by weight of collagen in the polymeric composition is less than 50%, where the percentage by weight of polyglyceryl-4-caprate in the polymeric composition is less than 6%, the rest would correspond to pullulan (up to 100% by weight of the polymeric mixture).

[0029] In another preferred embodiment, the polymeric fibers, of layers (A), (B) or (A') independently each one, are formed by a pullulan / elastin / collagen mixture where the percentage by weight of elastin is less than 10%, that of collagen is less than 50%, the rest would correspond to pullulan (up to 100% by weight of the polymeric mixture).

[0030] Preferably, in any of the aforementioned embodiments, the elastin is of plant origin (vegetable elastin), more preferably, the elastin is hydrolyzed wheat protein.

[0031] Preferably, in any of the aforementioned embodiments, the collagen is of non-animal origin such as collagen of microbial origin with or without genetic modification.

[0032] Preferably, in any of the aforementioned embodiments, the PEG is PEG 400, PEG-10, PEG-40 and PEG-60 hydrogenated castor oils, PEG-40 and PEG-100 stearates or PEG-20 oleate.

[0033] In a preferred embodiment, the polymeric fibers of layer (B) are formed from polymer blends selected from the list consisting of: pullulan / elastin; pullulan / polyethylene glycol (PEG); pullulan / elastin / collagen; or pullulan alone. The presence of bioactive agents in layer (B) is optional, and may contain the same or different bioactive agents and / or bioactive agent precursors as layer (A) and / or (A').

[0034] In a more preferred embodiment, the polymeric fibers of layer (B) are formed from a pullulan / elastin blend or from pullulan alone and do not comprise bioactive agents or precursors of bioactive agents. More preferably, the polymeric fibers of layers (A) and / or (A') are formed from pullulan / elastin.

[0035] In a preferred embodiment, the support layer (S) is formed by at least one layer of woven fibers, or non-woven fabrics (TNT) or a continuous film of one or more hydrophilic and / or hydrophobic polymers.

[0036] In a preferred embodiment, the support layer (S) comprises or consists of a continuous film based on polyvinyl alcohol (PVOH) and / or polysaccharides, with or without reinforcing additives or nanoadditives, preferably the support layer comprises or consists of starch or cellulose, for example and not limited to cellulose acetate; or in fabrics or nonwoven fabrics of PCL or PHA, as well as any combination of the above.

[0037] In an even more preferred embodiment, the support layer (S) comprises or consists of a biodegradable, compostable, transparent, continuous film based on starch with or without reinforcing additives or nanoadditives, where the starch content is greater than 80% by weight. In an even more preferred embodiment, the starch is enriched in amylose.

[0038] In the present invention, the areal density, typically expressed in g / m 2For each layer, the density is calculated by weighing a sample with known dimensions. This weight is then divided by the sample's surface area. This process is performed on at least five samples from each layer in order to obtain an average surface density value for the entire layer. In the present invention, the term "encapsulation" refers to the highly dispersed and distributed incorporation of the bioactive into the polymer fibers that make up each of the layers of the product containing it, either by forming a separate core-shell phase or by constituting a physical mixture with the fiber's polymeric material, including what are known as solid solutions or dispersions; the bioactive can therefore be found both inside and on the surface of said fibers, or even in the interstitial spaces between them.

[0039] In a preferred embodiment, the product of the invention consists of a layer of polymeric fibers (A) carrying bioactive agents and / or precursors of bioactive agents that will come into contact with the skin, a layer (B) immediately above layer (A), and a support layer (S). These will be multilayer structures: ABS.

[0040] In another preferred embodiment, the product of the invention consists of a layer of polymeric fibers (A) carrying bioactive agents and / or precursors of bioactive agents that will come into contact with the skin, a second layer of polymeric fibers (A') carrying bioactive agents and / or precursors of bioactive agents, a third layer of polymeric fibers (B) and a support layer (S) on which the previous layers are located. They will be multilayer structures: A-A'-BS.

[0041] In a preferred embodiment, the surface density of layer (A) or the sum of the surface densities of layers (A) and (A') is equal to or greater than the surface density of layer (B).

[0042] In the present invention, the term “bioactive” refers, without limitation, to any natural or synthetic substance that is beneficial to the skin and, more preferably, for use in cosmetics.

[0043] The bioactive agents that can be used in the products of the present invention are selected, without limitation, from any cosmetic bioactive that fulfills any of the following functions or combination of functions:

[0044] Anti-wrinkle: such as peptides, botox-like bioactives (for example and in a limited sense, botulinum toxin type A, spilanthes acmella also known as biobotox, dermatorelaxants such as some polypeptides (tri, tetra, penta, octapeptides), marine derivatives such as DMAE (dimethylaminoethanol), Tsubaki oil, acetyl hexapeptide-8 (also known as argireline (Acetyl Hexapeptide-3)), or an improved version of the latter, known as SNAP-8, wakame seaweed extract, bakuchiol, etc.

[0045] • Firming: such as dimethylaminoethanol (DMAE), niacinamide (vitamin B3), collagen, elastin, etc.

[0046] • Soothing / Anti-irritation: such as Vitamin B12, cannabidiol (CBD), aloe vera extract, ceramides, etc.

[0047] • Antibacterials: such as azelaic acid, salicylic acid, melic acid, tea tree oil, etc.

[0048] • Cleanser: such as surfactants, betaine, coco glycosides, saponins, etc.

[0049] • Nutritious: such as shea butter, almond oil, argan oil, vitamin E, etc.

[0050] • Decongestant: such as caffeine, guarana extract, ginseng extract, ginger extract, etc.

[0051] • Antioxidants: such as carotenoids, isoflavones, vitamin C, phytosterols, etc.

[0052] • Depigmentants: such as glycolic acid, kojic acid, hydroxytyrosol, arbutin, etc.

[0053] • Regenerators: such as centella asiatica, epidermal growth factors, retinol, retinal, etc.

[0054] • Rejuvenating or anti-aging: such as coenzyme Q10, jojoba oil, royal jelly, rosehip extract, etc.

[0055] • Moisturizing: such as hyaluronic acid, mucopolysaccharides, squalane, provitamin B, etc.

[0056] • Emollient: such as oat extract, coconut oil, cucumber extract, sesame oil, etc.

[0057] • Illuminator: such as vitamin C, ferulic acid, lactic acid, mandelic acid, etc.

[0058] • Anti-glare: such as activated carbon, silica, clays such as bentonites, volcanic rock, etc.

[0059] • Sebum regulator: azeloglycine, silicon, witch hazel extract, benzoyl peroxide, etc. Aromatizers: essential oils of Lemon, Tea Tree, Lavender, Mint, Rosemary, etc.

[0060] In another preferred embodiment, the bioactive agents and precursors of the bioactive agents used are of synthetic, natural, biotechnological origin, such as, for example, by fermentation and / or recombinant, and may be, without limitation, pure, mixed, liposomal or dissolved in natural deep eutectic solvents (NADES), as well as any mixture of all of the above.

[0061] In another preferred embodiment, the bioactive agents and precursors of the bioactive agents used are derivatives or extracts of biomass, waste or agri-food by-products, or any combination of the above.

[0062] In another preferred embodiment, the bioactive agents used are derived from by-products of olive oil production rich in hydroxytyrosol.

[0063] In the present invention, the term “precursor of the bioactive agent” refers to any substance that reacts with moistened skin to create in situ the bioactive agent with cosmetic power or at least two substances that, being encapsulated in the polymeric fibers, are released together (from the same layer) or separately (from different layers) and react with themselves to create in situ on moistened skin the bioactive agent with cosmetic power.

[0064] The precursors of bioactive agents that can be used in the products of the present invention are selected, without limitation, from any biological substrate, preferably natural, for example and without limitation enzymes, coenzymes and microorganisms or their products such as exosomes or extracellular vesicles that are transformed or react with any type of molecule, preferably of natural origin, to give rise to one or several bioactive substances with cosmetic functionality.

[0065] In a preferred embodiment, the precursor substances of bioactive agents that are encapsulated in the polymeric fibers of layer (A) are enzymes and those that are encapsulated in the polymeric fibers of layer (A') are natural extracts, or vice versa, which react when released onto the skin and generate one or more bioactive agents with cosmetic functionality.

[0066] In an even more preferred embodiment, the precursor substance encapsulated in the polymeric fibers of layer (A) is the enzyme myrosinase, and the precursor substance encapsulated in the polymeric fibers of layer (A') is any extract of cruciferous plants rich in the glucosinolate called glucoraphanin, or vice versa, which react in the skin to form in situ the bioactive molecule sulforaphane with cosmetic power. The amount of enzyme used in the product for the "in situ" creation on the skin of the bioactive molecule sulforaphane is that which leads to the greatest antioxidant capacity.

[0067] In the present invention, the term "polymer" refers to macromolecular materials of natural, synthetic or biotechnological origin, both in their pure ex-reactor state and as additives and post-processed in commercial formulas typically used by the chemical industry, more commonly known as plastic grades. Process additives, solubility and biodegradability promoters or stability enhancers, or other types of filler-type additives, may additionally be added to any of the polymers or plastic grades, either in micro, submicro or nanometric form, to improve their physicochemical properties or their capacity for retention and controlled release of bioactive agents and / or precursors of bioactive agents. Such additives may be of the chemical, fiber, sheet or particle type.

[0068] In another preferred embodiment, any of the layers of the product of the invention may comprise aromatic substances or aroma enhancers.

[0069] The product of the invention may also comprise a logo-type printing pigment or ink, either multicolor or monochrome, as a differentiating element on the sides of the product. In this case, the inks or pigments used are non-toxic, biocompatible, with good organoleptic properties, and do not affect the integrity of the product or the encapsulated bioactive. Any type of printing or stamping may be used, as long as it does not affect the integrity of the product's materials or the encapsulated bioactive. It may also have some type of texture.

[0070] On the other hand, the product of the invention can have any size and shape or flat pattern, made by any conventional cutting process, whether manual, using a die-cutting system, or laser cutting.

[0071] As for the manufacture of the fibers that make up the layers of the product of the invention, it is preferably carried out by any of the known electro-hydrodynamic and aero-hydrodynamic techniques for obtaining fibers, more preferably by electrodrawing (electrospinning), direct beam printing by electro-hydrodynamic processing (electrohydrodynamic direct writing), electrodrawing from the melt (melt electrospinning), stretching by blowing (solution blow spinning), as well as by any combination and / or vahant thereof. However, any other method for obtaining fibers may also be used, such as stretching by centrifugal beam (centrifugal jet spinning) or the combination of this and the aforementioned.Electrohydrodynamic and aerohydrodynamic techniques are based on the formation of polymeric micro or submicrofibers at room temperature or below, from a polymeric solution, suspension, or emulsion to which an electric field or gas pressure is applied. The fact that it can be processed in liquid form makes it highly versatile, allowing for the simultaneous incorporation of various substances. At the same time, its processability at room temperature avoids certain problems such as the degradation of the bioactive agent or its precursors.

[0072] In a preferred embodiment, the product of the invention is manufactured using the electrospinning technique. In an even more preferred embodiment, electrospinning is carried out using multi-outlet or multi-emitter injectors, whether needle-type or similar, or made of porous materials. The advantage of these injectors over so-called free-surface injectors that do not have a controlled outlet, also known as needleless electrospinning or free-surface electrospinning, is greater control over the diameter and distribution of the fiber diameter, as well as homogeneity along the thickness. Control over fiber diameter distribution facilitates reproducibility in release kinetics and, therefore, cosmetic certification.

[0073] In a preferred embodiment, the variation in fiber diameter is less than 35%, i.e., the variation in fiber diameter is less than ±17.5% of the mean value. This value is measured by scanning electron microscopy (SEM). In another preferred embodiment, the variation in fiber diameter for a given system with a multi-outlet injector is at least 15% less than that which would occur with uncontrolled outlet injectors.

[0074] In another even more preferred embodiment, the variation in fiber diameter for a given system with a multi-outlet injector is at least 5% less than that which would occur with uncontrolled outlet injectors.

[0075] Using these techniques and the aforementioned polymers, the present invention encapsulates the bioactive agent(s) and / or the precursor(s) of the bioactive agents in such a way that their release can also be sustained. To carry out this encapsulation, techniques are used, including, but not limited to: core-shell technology, co-deposition, surface modification electrospinning, side-by-side electrospinning to generate Janus-type structures, direct mixing, emulsion techniques, particle pre-encapsulation, layer-by-layer deposition, etc.

[0076] In the present invention, core-shell technology is used in the case of electrospinning and solution blow spinning, making use of a concentric nozzle through which one or more vapors of bioactive agents and / or one or more vapors of precursors of the bioactive agents in solution are supplied through the inner tube with or without encapsulating polymers, while the same or other encapsulating polymers and optionally the same and / or other bioactive agents and / or precursors of bioactive agents, are passed through the outer tube, or vice versa. The use of nozzles with more than two concentric tubes (triaxial or similar) can give rise to more combinations of bioactives, precursors and polymers. In any case, this technology can give rise to tubular fibers that can contain different bioactive agents and / or different precursors of bioactive agents in the inner layer and in the outer layer of the coaxial or multiaxial fiber.It also allows, depending on the design, to create fibers with controlled release profiles of bioactive agents or bioactive agent precursors. In the present invention, co-deposition consists of a deposition process in which two injectors simultaneously deposit identical or different fibers, for example, on the one hand, a polymer solution with one or more bioactive agents and / or with one or more bioactive agent precursors and, on the other hand, the same or another polymer solution with the same or other bioactive agents and / or bioactive agent precursors. This technique is used to separate incompatible or potentially reactive bioactive agents or bioactive agent precursors and / or to control their release.It is also used by depositing two solutions containing different types of polymers, thus generating different fiber sizes and morphologies within a single membrane, and therefore a different release profile of the bioactive agent(s) and precursors. Co-deposition can also be performed using fibers, particles, and / or mixtures of the two. Therefore, co-deposition or simultaneous electrospinning allows for the combination of various compositions and properties within the same layer.

[0077] In the present invention, the direct mixing can be, without limitation, the encapsulant and the encapsulating agent, or a suspension of particles containing the pre-encapsulated bioactive or precursor and the encapsulating agent, by means of monoaxial electrospinning, resulting in cylindrical fibers in which the bioactive or precursor is embedded and dispersed within the fiber. This mixture can be a homogeneous solution or a heterogeneous suspension.

[0078] In the present invention, emulsion techniques refer to any emulsion, without limitation, of solvents or components, which result in an encapsulation with various phases and are processed by processes known as electrohydrodynamic or aerohydrodynamic emulsion processing. An emulsion is a dispersion of a liquid (dispersed phase) in the form of tiny droplets within another liquid (continuous phase) with which it is generally not miscible. Emulsions can be direct, inverse, or multiple. Direct emulsions are those in which the dispersed phase is a lipophilic substance and the continuous phase is hydrophilic. These emulsions are usually referred to as L / H or O / W. Inverse emulsions, on the other hand, are those in which the dispersed phase is a hydrophilic substance and the continuous phase is lipophilic. These emulsions are usually abbreviated as H / L or W / O. They can also be 0 / 0 emulsions, with two immiscible organic phases.Multiple emulsions are those that, for example, contain an inverse emulsion as the dispersed phase and an aqueous liquid as the continuous phase. Multiple emulsions can be H / L / H or W / O / W or O / W / O. Emulsions can also be formulated using so-called Pickering emulsions, which use particles to separate and stabilize the phases, and any other type of emulsion technology. In this way, the bioactive agent and / or the bioactive agent precursor are encapsulated within the fibers in one of the phases, typically in the organic phase, and the release can also occur in a controlled manner.

[0079] In the present invention, use may also be made of pre-incorporation technologies for the functionalization, stabilization or separation of active agents and / or precursors of bioactive agents within liposomes, nanoliposomes, NADES, solid lipid particles and nanoparticles, or inclusion complexes, for example in cyclodextrins. Additionally, pre-encapsulation may also make use of any other encapsulation process that produces particles such as, and not limited to, electrospray, air-assisted electrospray (EAPG), coacervation, emulsion-evaporation / emulsion-extraction, hot melt, interfacial polycondensation, complexation, gelation, fluid bed, atomization, lyophilization, extrusion, electrostatic proplet generation, supercritical fluids, TROMS, etc., and mixtures thereof.These particles with bioactive ingredients and / or precursors are typically added, in the case of direct mixing, to a solution of the selected biopolymer or polymers, such that, after any of the aforementioned processes, fibers with particles inside are obtained. In this case, the controlled release procedure from the encapsulation is carried out by dissolution, diffusion, or opening of the particles and fibers, or even by combining vapors of the above mechanisms.

[0080] In the present invention, the layer-by-layer deposition method consists of using a process in which the layers are deposited sequentially. Thus, initially, layer (B) is deposited on the support layer (S) until the desired surface density is reached and then the following layers (A') and (A) are deposited, obtaining a multilayer product in situ.

[0081] Therefore, another aspect of the invention relates to a process for obtaining the product described in the present invention, where said process is based on the electrospinning technique (i.e., electrospinning) comprising: preparation of each layer of fibers from a solution, suspension or emulsion of the polymer or mixture of polymers that will form the fibers where the polymer or mixture of polymers is at a concentration of between 0.1 and 60% by weight; the voltage of the emitter used is between 0.01 and 500 kV and a voltage at the collector of between 0 kV and -500 kV, with a flow rate of between 0.0001 and 50,000 ml / h, at a temperature of between 1 e C and 100 e C, more preferably between 20 and 40 e C; and a relative humidity between 10 and 60% and more preferably between 15 and 40%.

[0082] When the layers carry bioactive agents and / or precursors of bioactive agents, these are added to the solution, suspension or emulsion of the polymer or polymer mixture. Preferably, the bioactive agent(s) and / or the precursor(s) of bioactive agents are present in a total concentration of between 0.0001 and 70% by weight in said solution, suspension or emulsion.

[0083] Preferably, a solution of the polymer or polymer mixture is prepared, choosing a solvent in which the polymers are soluble at the temperature at which the process is carried out. Preferred solvents are water and alcohols, such as methane, ethanol, isopropanol, butanol, and thiofluoroethanol, or any mixture thereof; more preferably, the solvent used is water.

[0084] When the polymer that makes up the fibers is not chemically compatible with the bioactive agent or precursor to be encapsulated (there is no physical-chemical interaction between them) or these have low or very low solubility in the solvent or solvents of the biopolymer necessary to carry out the manufacturing process of the product, then any known emulsion route can be used to encapsulate the bioactive agent(s) and / or the precursor(s) of the active agents, instead of the direct dissolution or suspension of these. The solvents are preferably water or alcohols (such as methane, ethanol, isopropanol, butanol and thiofluoroethanol), or any mixture of the above.

[0085] In a preferred embodiment, the layers of polymeric fibers are prepared layer by layer in the following order: first layer (B) on the substrate layer (S), then layer (A') and finally layer (A). The substrate (S) is as defined above. Alternatively, the various layers can also be obtained separately, and laminated to obtain the product of the invention, ABS or A-A'-BS, using any known lamination process. The present invention also relates to the cosmetic use of the cosmetic product of the present invention based on water-soluble polymers which by themselves already produce an inherently beneficial effect of cosmeticity on the skin, as well as to the complete or almost complete delivery of one or more bioactive agent vapors and / or of one or more bioactive agent precursor vapors present in the product, into the skin.

[0086] The term "inherently beneficial cosmetic effect" implies that the product itself, even if based solely on water-soluble polymers, is capable of producing a beneficial cosmetic effect on the skin. A "beneficial cosmetic effect" refers to a smoothing, firming, soothing, anti-irritation, anti-wrinkle, and moisturizing effect.

[0087] Therefore, another aspect of the present invention relates to the cosmetic use of the product defined in the present invention as a patch or mask to produce a beneficial cosmetic effect on moistened skin and for the controlled release of one or more bioactive agent vapors and / or one or more precursor vapors of bioactive agents on the moistened skin.

[0088] Another aspect of the invention relates to a cosmetic method for using the product described in the present invention for its preferred application on the skin: where the method comprises: (i) moistening or spraying the skin with any type of water, including thermal waters, at any temperature or with a cosmetic mist, (ii) the product is then applied to the skin by bringing layer (A) into contact with it, (iii) the product is then kept on the skin for a few seconds, at least 3 seconds, preferably between 3 and 5 seconds, and (iv) finally, layer (S) is carefully removed and discarded.

[0089] The term "moistened skin" refers in the present invention to the skin treated according to step (i) of the method described above. In a preferred embodiment, the skin is moistened with a cosmetic mist.

[0090] Preferably during the application process, layers (A) and (A') will be mostly or completely absorbed onto the skin releasing the bioactive agents and / or precursors of the bioactive agents and the sacrificial layer (B) will be mostly retained on the substrate (S) and layer (B) could be removed together with layer (S).

[0091] Another aspect of the invention relates to a kit comprising the cosmetic product described above and a water-based spray container (also known as a mist) with or without other cosmetic, balsamic, and / or fragrance products. The spray device allows the skin to be moistened before applying the cosmetic product so that it adheres to the skin easily and dissolves on its surface.

[0092] Throughout the description and claims, the word "comprise" and its variants are not intended to exclude other technical features, additives, components, or steps. For those skilled in the art, other objects, advantages, and features of the invention will be apparent in part from the description and in part from the practice of the invention. The following examples and figures are provided for illustrative purposes only and are not intended to limit the scope of the present invention.

[0093] BRIEF DESCRIPTION OF THE FIGURES

[0094] Fig. 1. Shows the different multi-layer configurations of the product of the invention.

[0095] Fig. 2. Shows patches of the cosmetic product described in example 1.

[0096] Fig. 3. Shows a mask of the cosmetic product described in example 1.

[0097] Fig. 4. Shows the viability of the keratinocyte cell line (HaCaT) after 24 hours of incubation according to the Resazuhna test in contact with the patch of example 1.

[0098] Fig. 5. Shows the quantification of reactive oxygen species (ROS) in the form of arbitrary fluorescence units (AFU) per microgram of total protein of the keratinocyte cell line (HaCaT) after 24 hours in contact with the patch of example 1.

[0099] EXAMPLES

[0100] The invention will now be illustrated by some examples provided by the inventors, which demonstrate the effectiveness of the product of the invention.

[0101] Example 1: Multi-layer cosmetic product of pullulan / elastin (B), pullulan / elastin / hydroxytyrosol-rich extract (A) on a starch-based substrate film (S).

[0102] The hydrophilic fibers with encapsulated bioactive were deposited on the starch-based film (100 µm thick) placed on a rotating collector (200 rpm). This manufacturing was carried out using the electrospinning technique in a 5-needle linear multi-outlet injector, at a temperature of 30 ° C. e C and a relative humidity of 30%.

[0103] To do this, a solution of pullulan at 14.55% by weight (wt.%), 0.45% of hydrolyzed wheat protein (vegetable elastin) in deionized water was used to generate a first layer (B) with a surface density of 2 g / m 2 To produce the fiber mesh, an emitter voltage of 28kV was used, as well as a collector voltage of -25k, and a flow rate of 5 ml / h.

[0104] On top of the previous layer, a second layer of fibers (A) was deposited starting from a 14.55% by weight (wt.%) pullulan solution, 0.45% hydrolyzed wheat protein (vegetable elastin), and 0.2688% of a hydroxytyrosol-rich extract, in deionized water. In this polymer solution, the polymer:bioactive ratio was 98.24:1.76. For this purpose, an emitter voltage of 28 kV was used, as well as a collector voltage of - 25 kV, and a flow rate of 5 ml / h, with a surface density of 3 g / m 2 .

[0105] The product in this example was cut into different shapes to be applied to different parts of the facial skin as shown in Figures 2 and 3. Using HPLC it was found that after applying the product to the forehead skin of three volunteers for three seconds moistened with a mist, less than 10% of the hydroxytyrol in the patch was retained on the substrate (S).

[0106] Figure 4 indicates, through in vitro testing, that the cosmetic product is not cytotoxic to the skin, as keratinocyte viability is not reduced after 24 hours of contact with the dissolved material of the cosmetic patch. Figure 5 indicates that the cosmetic product has a significant capacity to reduce the production of reactive oxygen species and therefore has an anti-aging effect.

[0107] Example 2: Multi-layer cosmetic product of pullulan (B), pullulan / elastin / hydroxytyrosol-rich extract and hyaluronic acid (A) on a starch-based substrate film (S).

[0108] Hydrophilic fibers with encapsulated bioactive were deposited on the starch film (100 µm thick) placed on a rotating collector (200 rpm). This manufacturing was carried out using the electrospinning technique in a 5-needle linear multi-outlet injector, at a temperature of 30 ° C. eC and a relative humidity of 30%.

[0109] To do this, a 15% by weight (wt.%) pullulan solution in deionized water was used to generate a first layer B with a surface density of 2 g / m 2 To produce the fiber mesh, an emitter voltage of 28 kV was used, as well as a collector voltage of -25 kV, and a flow rate of 5 ml / h.

[0110] Another layer of fibers was deposited on the previous layer, starting from a solution of pullulan at 14.55% by weight (wt.%), 0.45% hydrolyzed wheat protein (vegetable elastin), 0.271% of an extract rich in hydroxytyrosol and 0.155% hyaluronic acid of 5 kDa molecular weight, in deionized water. In this solution, the polymer:bioactive ratio was 97.24:2.76. To produce this second layer of fibers (A), an emitter voltage of 28 kV was used, as well as a collector voltage of -25 kV, and a flow rate of 5 ml / h, with a surface density of 3 g / m 2 .

[0111] Example 3: Multilayer cosmetic product of pullulan / elastin (B), pullulan / elastin / broccoli extract (A') and pullulan / elastin / myrosinase (A) on a starch-based substrate film (S).

[0112] Hydrophilic fibers with encapsulated bioactive were deposited on the starch film (100 µm thick) placed on a rotating collector (200 rpm). This manufacturing was carried out using the electrospinning technique in a 5-needle linear multi-outlet injector, at a temperature of 30 ° C. e C and a relative humidity of 30%.

[0113] To do this, a solution of pullulan at 14.55% by weight (wt.%), 0.45% of hydrolyzed wheat protein (vegetable elastin) in deionized water was used to generate a first layer B with a surface density of 3 g / m 2. To produce the fiber mat, an emitter voltage of 28 kV was used, as well as a collector voltage of -25 kV, and a flow rate of 5 ml / h. On top of the previous layer, another layer of fibers (A') was deposited starting from a solution of pullulan at 14.55% by weight (wt.%), 0.45% hydrolyzed wheat protein (vegetable elastin) and 3.52% broccoli extract, in deionized water. In this solution, the polymer:bioactive ratio was 96.47:3.53. To produce this second layer of fibers (A'), an emitter voltage of 28 kV was used, as well as a collector voltage of -25 kV, and a flow rate of 5 ml / h, with a surface density of 3.2 g / m 2 .

[0114] Another layer of fibers (A) was deposited on the previous layer, starting from a solution of 14.55% by weight (wt.%) pullulan, 0.45% hydrolyzed wheat protein (vegetable elastin), and 0.5% of the myrosinase enzyme, in deionized water. In this solution, the polymer:bioactive ratio was 99.994:0.006. To produce this second layer of fibers (A), an emitter voltage of 28 kV was used, as well as a collector voltage of -25 kV, and a flow rate of 5 ml / h, with a surface density of 0.8 g / m 2 The amount of enzyme used for the in situ creation of the antioxidant bioactive molecule on the skin was optimized to obtain the highest antioxidant value measured according to the in vitro DPPH method.

[0115] In this type of patch, the water-soluble layers containing the two precursors, extract and enzyme, are solubilized in moistened skin to react and create the bioactive molecule sulforaphane "in situ."

Claims

CLAIMS 1. A self-adhesive cosmetic product for application to moistened skin, wherein the product comprises: - a layer of polymeric fibers (A) which is the layer in contact with the skin, where the fibers have an average diameter size between 50 nm and 5 pm; and are made up of at least one water-soluble polymer selected from polysaccharides, proteins, and any mixtures thereof and, where it additionally comprises at least one bioactive agent and / or at least one precursor of a bioactive agent encapsulated in the layer (A), - a sacrificial layer of polymeric fibers (B), where the fibers have an average diameter size between 50 nm and 5 pm; and are made up of at least one water-soluble polymer selected from polysaccharides, proteins, and any mixtures thereof and where it optionally comprises at least one bioactive agent and / or at least one precursor of a bioactive agent encapsulated in the layer (B), and - a support layer or substrate (S), characterized in that the substrate comprises a material that is insoluble in water or has a lower solubility than the layers (B) and (A), and on which the layers of polymeric fibers (B) and (A) are located, thus forming a structure, from the skin outwards, (A)-(B)-(S).

2. The cosmetic product according to claim 1, wherein the product additionally comprises a layer of polymeric fibers (A'), arranged between layers (A) and (B), where the fibers have an average diameter size between 50 nm and 5 pm; and are made up of at least one water-soluble polymer selected from polysaccharides, proteins, and any mixtures thereof and which additionally comprises at least one bioactive agent and / or at least one precursor of a bioactive agent encapsulated in layer (A').

3. The cosmetic product, according to claim 1 or 2, wherein the polymeric fibers, of layers (A), (B) or (A') independently each one, are made up of pullulan, fructan, fucopol, cashew gum, elastin, collagen or any of their combinations.

4. The cosmetic product according to any one of claims 1 to 3, wherein the polymeric fibers of the layers (A), (B) or (A') independently each, Additionally, they are made up of a polymer selected from PEG, NADES, polyglyceryl-4-caprate and any of their combinations.

5. The cosmetic product according to any of claims 1 to 4, wherein the polymeric fibers of at least one of the layers (A), (A') and (B) are formed by a pullulan / elastin mixture where the percentage by weight of elastin in the polymeric composition is less than 10% and the remainder corresponds to pullulan.

6. The cosmetic product according to any of claims 1 to 4, wherein the polymeric fibers of at least one of the layers (A), (A') and (B) are formed by a pullulan / PEG mixture where the percentage by weight of PEG in the polymeric composition is less than 30% and the remainder corresponds to pullulan.

7. The cosmetic product according to any of claims 1 to 4, wherein the polymeric fibers of at least one of the layers (A), (A') and (B) are formed by a pullulan / collagen mixture where the percentage by weight of collagen in the polymeric composition is less than 50% and the remainder corresponds to pullulan.

8. The cosmetic product according to any of claims 1 to 4, wherein the polymeric fibers of at least one of the layers (A), (A') and (B) are formed by a pullulan / collagen / polyglyceryl-4-caprate mixture where the percentage by weight of collagen in the polymeric composition is less than 50%, where the percentage by weight of polyglyceryl-4-caprate in the polymeric composition is less than 6% and the remainder would correspond to pullulan.

9. The cosmetic product according to any of claims 1 to 4, wherein the polymeric fibers of at least one of the layers (A), (A') and (B) are formed by a pullulan / elastin / collagen mixture and the percentage by weight of elastin in the polymeric mixture is less than 10%, that of collagen is less than 50% and the remainder corresponds to pullulan.

10. The cosmetic product according to any of claims 1 to 4, wherein the polymeric fibers of layer (B) are formed by a pullulan / elastin mixture or only by pullulan and do not comprise bioactive agents or precursors of bioactive agents. 1 1. The cosmetic product according to any of claims 3, 5, 9 and 10, wherein the elastin is vegetable elastin.

12. The cosmetic product according to claim 11, wherein the vegetable elastin is hydrolyzed wheat protein.

13. The cosmetic product according to any of claims 1 to 12, wherein the support or substrate layer (S) consists of a continuous biodegradable, compostable and transparent film comprising more than 80% by weight of starch.

14. The cosmetic product according to any of claims 1 to 13, wherein the fibers of any of the layers are obtained by electro-hydrodynamic, aero-hydrodynamic techniques or a combination thereof.

15. The cosmetic product according to claim 14, wherein the fibers of any of the layers are obtained by electro-stretching.

16. The cosmetic product according to any one of claims 1 to 15, wherein the surface density of the layer (A) or the sum of the surface densities of the layers (A) and (A') is equal to or greater than the surface density of the layer (B).

17. Cosmetic product according to any of claims 2 to 16, wherein the precursor substance of the bioactive agent comprising the polymeric fibers of layer (A) is the enzyme myrosinase, and the one comprising the polymeric fibers of layer (A') is a cruciferous extract containing glucoraphanin, or vice versa.

18. Method for obtaining the cosmetic product defined in any of claims 1 to 17, wherein said method is based on the electrospinning technique comprising: preparing each layer of fibers from a solution, suspension or emulsion of the water-soluble polymer or mixture of polymers that will form the fibers where the polymer or mixture of polymers is at a concentration of between 0.1 and 60% by weight; the voltage of the emitter used is between 0.01 and 500 kV and a voltage in the collector of between 0 kV and -500 kV, with a flow rate of between 0.0001 to 50,000 ml / h, at a temperature between 1 and 100 e C and a relative humidity between 10 and 60%; and adding to the solution, suspension or emulsion of layer (A) at least one agent bioactive, at least one bioactive agent precursor or any combination thereof at a total concentration between 0.0001 and 70% by weight in said solution, suspension or emulsion.

19. Method according to claim 18, wherein at least one bioactive agent, at least one bioactive agent precursor or any combination thereof is added to the solution, suspension or emulsion of layer (A') and / or (B) at a total concentration between 0.0001 and 70% by weight in said solution, suspension or emulsion.

20. Method according to claim 18 or 19, wherein the fiber layers (B), (A') and (A) are prepared layer by layer on a substrate layer (S).

21. Method according to any of claims 18 to 20, wherein controlled output, multi-output or multi-emitter injectors are used.

22. Cosmetic use of the product defined in any of claims 1 to 17 as a patch or mask to produce a beneficial cosmetic effect on moistened skin.

23. Cosmetic use of the product defined in any of claims 1 to 17, as a patch or mask for the controlled release of one or more bioactive agent vapors and / or one or more precursor vapors of bioactive agents on moistened skin.

24. Cosmetic method for using the product defined in any of claims 1 to 17, comprising: (i) moistening or spraying the skin with water, (ii) then applying the product to the skin (i) bringing the layer (A) into contact with it, (iii) then keeping the product on the skin for at least 3 seconds, preferably between 3 and 5 seconds, and (iv) removing the layer (S) and discarding it.

25. Kit comprising a cosmetic product, as described in any of claims 1 to 17, and a spray container comprising water or water with at least one cosmetic, balsamic, odorant product or any combination thereof.