EP4565185A1 - Article comprising a natural polymer-based patch product and corresponding production method - Google Patents

Abstract

The present invention concerns an article comprising a patch product disposed on a base support and which contains a membrane substrate absorbable by the skin formed by at least one electrospun fiber composed of a first compound to be electrospun and an electrospinning promoter.

Description

“ARTICLE COMPRISING A NATURAL POLYMER-BASED PATCH PRODUCT AND CORRESPONDING PRODUCTION METHOD”

FIELD OF THE INVENTION The present invention concerns an article containing a product. More in particular, the invention concerns a patch product absorbable by the skin and based on biocompatible polymer compounds, which is composed of fibers, in particular nanofibers, obtained preferably by means of electrospinning, which are deposited on a support and packaged. The support is also based on biocompatible polymer compounds, despite not being absorbable by the skin.

BACKGROUND OF THE INVENTION

Products to be applied directly on the skin are widely known, which are formulated in various forms compatible with the skin and/or which are absorbed by the skin, such as for example emulsions, creams, lotions, serums, gels, powders, oils, sunscreens and suchlike, or other formulations.

However, these products can sometimes be laborious to apply on the skin, sometimes requiring prolonged application times or a prolonged massage for a complete absorption into the dermis, and sometimes leaving residues on the fingers or hands or on any applicators used. There are also products, in particular cosmetics, applied by means of a physical support, generally fibrous, which facilitates their application on the skin, such as in particular make-up remover wipes, which are soaked in a special detergent composition.

One disadvantage of this type of products lies in the need to also dispose, after use, of the fibrous physical support, as well as of the package, the former having no function other than that of support.

Furthermore, known fibrous physical supports have a specific surface that does not allow a suitable transport and release of the active ingredients.

The question also arises that, generally, cosmetic compositions for the skin, for example those to be spread, such as cream, or in general pastes, provide the use of compounds which are functional for the skin and compounds which are exclusively functional for the structure of the formulation.

The compounds which are functional for the skin are partly, or completely, absorbed by the skin and benefit the treated body parts. In general, this type of compounds represents the so-called active ingredients.

The compounds which are exclusively functional for the structure of the formulation contribute to obtaining the composition to be applied, whether it is an emulsion, a serum or fluid, an oleolite, a water, or a gel.

The effects of a compound that is exclusively functional for the structure of the formulation can affect the way the composition is stored, or the consistency of the composition before its use and/or at the time of use, therefore when it is spread on the skin to be treated. For example, a compound that is exclusively functional for the structure of the formulation can make the composition soft, fluid or viscous; it can allow to obtain a gel, or prevent a separation between the oily and aqueous compounds in an emulsion. Moreover, exclusively functional compounds allow the preservation of the composition, especially in the presence of water. The problem arises that numerous compounds used, since they are functional for the structure of the formulation, do not however bring any benefit to the skin, indeed they can even lead to a further worsening of the treated skin. In fact, a part of the compounds that are exclusively functional for the structure of the formulation remain indifferent to the skin, or may cause, for example, further dryness, pore closure, or development of allergies, dermatitis, or suchlike.

Among the compounds that are exclusively functional for the structure of the formulation it is possible to identify, for example, silicones, petroleum products (for example paraffin), alcohols, perfumes, stabilizers, preservatives, emulsifiers, whose main function is to give the formulation of the composition a “silky effect” consistency in contact with the skin and/or to give stability to the oily parts, or to increase the viscosity of gel formulations and/or to increase the emollient and humectant effect of the emulsions.

For example, a problem that arises with such compounds that are exclusively functional for the structure of the formulation is the lack of dermo compatibility, preventing the skin from breathing even leading, for example, to its progressive drying, pore closure and/or increased sensitization.

It is also known that the presence of alcohols and preservatives allow on the one hand the preservation of the composition, yet on the other hand they increase the sensitization of the skin in developing dermatitis, allergies, or similar pathologies.

An article is known from WO 2021/161256 comprising a cosmetic patch product based on fibers made of biocompatible material absorbable by the skin, which are deposited on a support made of heat-sealable plastic material, in particular polybutylene succinate adipate PBSA or polylactic acid PLA.

Such a patch product solves some of the problems mentioned above, but still does not fully meet the needs of the industry, because the material used is not fully biodegradable. Moreover, it has a stiffness such that it does not allow a good application of the product, in particular on some areas of the face where the surface is not flat, such as the nose area.

There is therefore the need to perfect a product that can overcome at least one of the disadvantages of the state of the art.

In particular, one purpose of the present invention is to provide a product which can be applied simply and quickly on the skin in any area of the body. Another purpose of the present invention is to provide a product which is provided with a biodegradable physical support.

Another purpose is to provide a product which has a specific surface such as to optimize the transport and release of active ingredients, if present.

The Applicant has devised, tested and embodied the present invention to overcome the shortcomings of the state of the art and to obtain these and other purposes and advantages.

SUMMARY OF THE INVENTION

The present invention is set forth and characterized in the independent claims. The dependent claims describe other characteristics of the present invention or variants to the main inventive idea.

In accordance with the above purposes and to resolve the technical problem disclosed above in a new and original way, also achieving considerable advantages compared to the state of the prior art, an article according to the present invention comprises a patch product containing a membrane substrate absorbable by the skin formed by at least one electrospun fiber composed of a first compound to be electrospun and an electrospinning promoter, and a base support on which the patch product is deposited.

In accordance with one aspect of the present invention, the base support comprises a polysaccharide-based biodegradable film not absorbable by the skin. Preferably, the film is made of polysaccharide, that is, the polysaccharide is the material which constitutes the film. Advantageously, the polysaccharide is a starch.

In a particularly advantageous manner, the base support consists of a polysaccharide-based biodegradable film not absorbable by the skin.

Doing so achieves at least the advantage of having a base support that is biodegradable and compostable. The support in polysaccharide is by nature adaptable and shapeable when applied to the skin, in part due to its degree of water absorption which alters its rigidity and makes it softer. This allows to improve the application of the patch product on the skin in areas that have many reliefs, such as the nose area for example, and in any case ensures that the entire surface of the membrane substrate adheres to the skin, increasing its absorption rate. The base support at the base of the present invention is therefore also particularly useful on curved, convex or concave areas such as the forehead, temples, cheekbones, cheeks, eye contours or suchlike. As another advantage, since the support is in polysaccharide, it comprises numerous hydroxyl -OH groups which make it suitable for hydrating the skin. This hydrating effect combines with the hydrating effect of the membrane substrate, which dissolves and enters the skin with greater ease than a same membrane substrate placed on a support made of a conventional material.

Furthermore, the polysaccharide film, in particular made of starch, has good barrier properties, making it suitable to form a package for the patch product.

In accordance with some embodiments of the present invention, the starch is selected from corn starch, potato starch, rice starch, wheat starch, tapioca starch and mixtures thereof. Preferably, the ingredients of this group are not genetically modified.

Preferably, the starch has a high amylose content, that is, it has an amylose concentration greater than 50% by weight on the weight of the starch itself, more preferably the amylose concentration is greater than 60% by weight, even more preferentially greater than 70% by weight on the weight of the starch. Due to its more linear and longer structure, compared to amylopectin, amylose allows to facilitate the formation of starch-based films.

In accordance with other embodiments of the present invention, the polysaccharide-based film has a thickness of less than 1mm, preferably less than 0.5 mm.

In accordance with other embodiments of the present invention, the first compound to be electrospun is a polymer suitable to be electrospun and selected from a group consisting of a first polysaccharide, collagen, gelatin, albumin, elastin and derivatives thereof. Favorably, the first polysaccharide is selected from a group consisting of xanthan gum, pectin, chitin, chitosan, dextran, carrageenan, guar gum, agar, cellulose derivatives, starch, gelatin, [3-glucans, glycosaminoglycans, mucopolysaccharides, water-soluble polysaccharides and their derivatives. Preferably, the cellulose derivatives are selected from hydroxypropyl methylcellulose HPMC, hydroxypropyl cellulose HPC, hydroxyethyl cellulose HEC, sodium carboxymethyl cellulose Na-CMC. The glycosaminoglycans GAGs or mucopolysaccharides can be selected from chondroitin sulphate, dermatan sulphate, heparin, heparan sulphate and hyaluronic acid HA. The water-soluble polysaccharides can be selected from galactomannans, xylans, gum arabic, gum ghatti, glucomannan, acemannan, soluble dietary fibers, glycogen, amylose and polysaccharides derived from plants, bacteria and fungi.

According to other embodiments of the present invention, the spinning promoter is a vector polymer, possibly even without filler, selected from a group consisting of a second polysaccharide, chemically different from the first polysaccharide, possibly in the presence of poly(oxyethylene) PEG. Favorably, the vector polymer, possibly even without filler, is also biocompatible.

Preferably, the electrospinning promoter is selected from pullulan and alginate, possibly mixed with poly (oxy ethylene). The promoter can also comprise a mixture of pullulan and alginate. More preferably, the promoter is chemically different from the first compound to be electrospun, that is, the first compound to be electrospun is not pullulan or alginate.

In accordance with other embodiments of the present invention, the fiber is also composed of a surfactant. The surfactant is advantageously a biosurfactant, that is, a surfactant of biological and organic origin. In particular, the surfactant is obtained by fermentation of gram positive microorganisms. Such a surfactant has biological origins, which makes it biocompatible. Preferably, the surfactant is selected from lipopeptides, in particular obtained from Bacillus sp. More preferably, the surfactant is selected from the Surfactin family, in particular from the group consisting of Surfactins, Pumilacidins and Lichenysins. Advantageously, the surfactant is concentrated between 0.1 and 5%, more advantageously between 0.2 and 2%, even more advantageously between 0.5 and 1 % by weight on the total weight of the fiber.

In accordance with some embodiments of the present invention, the electrospun fiber has a flat ribbon shape. That is, the fiber has a section with an oblong, rather than circular, shape.

In accordance with some embodiments, the membrane substrate is in the form of a non-woven fabric.

In accordance with other embodiments, the membrane substrate contains one or more active ingredients selected from cosmetic active ingredients, pharmaceutical active ingredients and nutritional active ingredients. By the expression “active ingredients” we mean, here and in the present description, compounds that are functional for the body, or parts of it, which are partly or completely absorbed by the skin and bring benefits to the treated body parts.

Advantageously, the one or more active ingredients are selected from one or more peptides and their metabolites or derivatives. A class of peptides which can be used as active ingredients is the class of tetrapeptides and their metabolites or derivatives, preferably acetyl tetrapeptides and their metabolites or derivatives. Among acetyl tetrapeptides we can mention, for example, acetyl tetrapeptide-9 and acetyl tetrapeptide- 11, which are two anti-ageing active compounds that act, respectively, on the skin matrix to improve its structure and on the elasticity and firming of the skin.

In accordance with some embodiments, the one or more active ingredients comprise a humectant, such as mannitol for example, a pH adjuster, such as sodium hydroxide for example, and/or an anti-wrinkles compound, such as aminobutyric acid for example.

One advantage of the article according to the embodiments described here is that the patch product contained therein is completely absorbed by the skin, together with the active ingredient present, for example a cosmetic, pharmaceutical or nutritional active ingredient. In addition to being complete, the absorption is also fast, it has been verified that the total absorption of a patch product of the article according to the invention occurs in very few minutes from its application on the skin. Another advantage is that the form in which the article is presented does not imply formulations that require the presence of compounds which are exclusively functional for the structure, since the active ingredients are carried and conveyed by the membrane substrate and the latter is completely biocompatible and absorbable by the skin, without involving any risk or damage to the skin itself. Another advantage of the article with cosmetic, pharmaceutical or nutritional product lies in the possibility of reaching much higher topical concentrations of the compound of interest than those obtainable with traditional formulations. It is practically impossible to reach high concentrations, even with polysaccharides, collagen, gelatin, albumin, elastin and their low molecular weight derivatives, since the viscosity of the product increases too much and it is not possible to exceed

5-10% by weight. With this article, the cosmetic, pharmaceutical or nutritional products allow to apply concentrations of up to 50% by weight of the compound of interest on the skin.

According to another aspect of the present invention, a method for producing an article containing a patch product disposed on a base support comprises a step of electrospinning a composition comprising a first compound to be electrospun and an electrospinning promoter in order to obtain an electrospun fiber, wherein the electrospun fiber is directly deposited on a base support comprising a polysaccharide-based biodegradable film not absorbable by the skin, preferably made of starch.

In a particularly advantageous manner, the base support consists of the polysaccharide-based biodegradable film not absorbable by the skin.

In accordance with some embodiments of the present invention, the starch is selected from com starch, potato starch, rice starch, wheat starch, tapioca starch and mixtures thereof. Preferably, the ingredients of this group are not genetically modified.

Preferably, the starch has a high amylose content, that is, it has an amylose concentration greater than 50% by weight on the weight of the starch itself, more preferably the amylose concentration is greater than 60% by weight, even more preferably greater than 70% by weight on the weight of the starch. Due to its more linear and longer structure, compared to amylopectin, amylose allows to facilitate the formation of starch-based films. In accordance with other embodiments of the present invention, the polysaccharide-based film has a thickness of less than 1mm, preferably less than 0.5 mm.

Advantageously, the biocompatible polymer material to be electrospun and/or the electrospinning promoter are as indicated above. In accordance with some embodiments, the composition also comprises a surfactant.

The surfactant is advantageously a biosurfactant, that is, a surfactant of biological and organic origin. In particular, the surfactant is obtained by fermentation of gram positive microorganisms. Such a surfactant has biological origins, which makes it biocompatible.

Preferably, the surfactant is selected from lipopeptides, in particular obtained from Bacillus sp. More preferably, the surfactant is selected from the Surfactin family, in particular from the group consisting of Surfactins, Pumilacidins and Lichenysins. Advantageously, the surfactant is concentrated between 0.1 and 5%, more advantageously between 0.2 and 2%, even more advantageously between 0.5 and 1% by weight on the total weight of the fiber.

In accordance with other embodiments, the composition contains one or more active ingredients, selected from cosmetic active ingredients, pharmaceutical active ingredients and nutritional active ingredients.

Advantageously, the one or more active ingredients are selected from one or more peptides and their metabolites or derivatives. A class of peptides which can be used as active ingredient is the class of tetrapeptides and their metabolites or derivatives, preferably acetyl tetrapeptides and their metabolites or derivatives. Among acetyl tetrapeptides we can mention, for example, acetyl tetrapeptide-9 and acetyl tetrapeptide- 11 , which are two anti-ageing active compounds that act, respectively, on the skin matrix to improve its structure and on the elasticity and firming of the skin. In accordance with some embodiments, the one or more active ingredients comprise mannitol, a pH adjuster, such as sodium hydroxide for example, and/or an anti- wrinkles compound, such as aminobutyric acid for example.

According to another aspect of the present invention, a primary packaging comprises a hermetically closed sachet inside which there is enclosed an article as described above. According to some embodiments, the sachet is composed of two sheets of heat-sealable material which are reciprocally welded. Advantageously, the two sheets are welded in correspondence with a circumference thereof, in such a way as to form an internal space suitable to contain the article. According to another aspect of the present invention, a secondary packaging comprises a box and a plurality of primary packagings as above enclosed inside the box.

DESCRIPTION OF THE DRAWINGS

These and other aspects, characteristics and advantages of the present invention will become apparent from the following description of one embodiment, given as a non-restrictive example with reference to the attached drawings wherein:

- fig. 1 is a graphic representation of the evolution of skin hydration with the application of an article of the invention containing a patch product, and with the application of a placebo product; - fig. 2 is a graphic representation of the evolution of skin elasticity with the application of an article of the invention containing a patch product, and with the application of a placebo product;

- fig. 3 is a graphic representation of the evolution of collagen density in the skin with the application of an article of the invention containing a patch product, and with the application of a placebo product;

- figs. 4 and 5 are graphic representations of the evolution of the presence of collagen in the skin treated with an article of the invention containing a patch product, and the comparison with untreated skin.

We must clarify that in the present description the phraseology and terminology used, as well as the figures in the attached drawings also as described, have the sole function of better illustrating and explaining the present invention, their function being to provide a non-limiting example of the invention itself, since the scope of protection is defined by the claims. To facilitate comprehension, the same reference numbers have been used, where possible, to identify identical common elements in the drawings. It is understood that elements and characteristics of one embodiment can be conveniently combined or incorporated into other embodiments without further clarifications. DESCRIPTION OF SOME EMBODIMENTS OF THE PRESENT INVENTION Unless otherwise defined, all the technical and scientific terms used here and hereafter have the same meaning as commonly understood by a person with ordinary experience in the field of the art to which the present invention belongs. Even if methods and materials similar or equivalent to those described here can be used in practice and in the trials of the present invention, the methods and materials are described hereafter as an example. In the event of conflict, the present application shall prevail, including its definitions. The materials, methods and examples have a purely illustrative purpose and shall not be understood restrictively. All measurements are carried out at 25°C (ambient temperature) and at atmospheric pressure, unless otherwise indicated. All temperatures are in degrees Celsius, unless otherwise indicated.

All percentages and ratios reported here shall be understood to refer to the weight of the total composition (w/w), unless otherwise indicated. All percentage ranges reported here are given with the provision that the sum with respect to the overall composition is 100%, unless otherwise indicated.

All the intervals reported here shall be understood to include the extremes, including those that report an interval “between” two values, unless otherwise indicated. The present description also includes the intervals that derive from uniting or overlapping two or more intervals described, unless otherwise indicated.

The present description also includes the intervals that can derive from the combination of two or more values taken at different points, unless otherwise indicated. Where water is mentioned, this is to be understood as distilled water, unless otherwise specified.

An article according to the present invention comprises a patch product disposed on a base support. The patch product is to be applied on the skin and comprises an electrospun membrane substrate consisting of at least one electrospun fiber, in particular at least one nanofiber, in the form of a non-woven fabric. This form is obtained by the progressive deposit of the fiber, during the electrospinning, on a base support. The fiber is progressively deposited on several layers that gradually overlap. Multiple fibers can be provided, which can be for example delivered simultaneously on the same support.

The base support consists of a biodegradable film made of starch, in particular non-genetically modified com starch. Alternatively, starch from other ingredients, such as potato, wheat, tapioca, rice or suchlike, can be used, in particular if they are not genetically modified. It can also be provided that the base support has other layers of other materials associated with the biodegradable starch film.

The starch used may be of the high amylose content type. By high amylose content starch we mean a starch in which the amylose is at more than 50% by weight on the weight of the starch, in particular at more than 60%, more than 75%.

For example, the starch can contain about 80% by weight of amylose and 17% by weight of amylopectin. Please note that a “normal” starch contains about 17% amylose and 80% amylopectin.

The higher concentration in amylose, which has a substantially linear (unbranched) molecular structure and is longer than amylopectin, favors the formation of a more robust and stable film.

Typically, the starch film to be used for the base support can have a thickness comprised between 45pm and 110pm, in particular between 50pm and 100pm, be light in color and be provided in the form of reels having a width of about Im. The film has a density comprised between 1.35 and 1.45 g/cm³ (measured according to the ASTM D 792 standard), a Vicat softening temperature between 130°C and 135°C (measured according to the ASTM D 1525 standard), a glass transition temperature between 130°C and 135°C (measured with the DMA method at 50% humidity) and/or a water activity comprised between 0.50 and 0.65 (measured according to the PTM 03 method). Such a water activity value suggests that the starch film has a tendency to absorb water, which causes it to at least partly soften, which favors its deformation to better adhere to the skin in non-planar areas.

The film advantageously has an elastic modulus between 2000MPa and 3500MPa, preferably between 2800MPa and 3000MPa, a tensile strength between 25MPa and 60MPa, preferably between 35MPa and 50MPa, and a breaking stress greater than 20%. These values were measured in the machine direction (MD) according to the ASTM D882 standard. The film has a static friction coefficient between 0.15 and 0.25, preferably 0.21, and a dynamic friction coefficient between 0.10 and 0.25, preferably equal to 0.17. These friction coefficients are measured according to the STM D 1894 standard.

The film also has a water vapor transmission rate between 100 and 180g/m²/24 hours, preferably 140g/m²/24 hours at 38°C and 75% humidity (measured according to the ASTM E9600 standard), and an oxygen transmission rate between

1 and 2cc.25pm/m²/atm/day, preferably equal to 1.60cc.25pm/m²/atm/day at 50% humidity (measured according to the ASTM DI 434 standard).

Advantageously, the base support is transparent and allows to visualize the dissolution and absorption of the membrane substrate in the skin during application. Obviously, this assumes that the membrane substrate is not transparent. Advantageously, the film has a transparency between 3 and 20%, preferably between 6 and 10% (measured according to the ASTM DI 003 standard), a 60° specular gloss between 70% and 90%, preferably between 80% and 85% (measured according to the ASTM D2457 standard) and an optical transparency greater than 85%, preferably greater than 90%, more preferably between 95% and 98% (measured according to the ASTM DI 003 standard).

The electrospinning takes place by feeding a special composition under an electric field, through an electrospinning head. The fiber exiting from the electrospinning head is then deposited on a base support comprising a film made of starch. The non-woven fabric form can be obtained by means of a relative movement between the electrospinning head and the base support.

Preferably, the fiber is continuous, homogeneous in composition and with a substantially smooth surface. The fiber is also preferably defect-free, that is, free of accumulations or droplets of substrate that can form during the electrospinning. The electrospun fiber can have a flat ribbon shape, that is, have an oblongshaped cross-section.

Advantageously, the electrospun fiber has a section the maximum lateral size of which is of the order of a nanometer and a micrometer, yet still less than 100 pm, more preferably less than 50 pm, even more preferably less than 25 pm, at most of the order of 10 pm. The fibers of the substrate can have lateral sizes starting from ten nanometers, for example 50 nm. Please note that the lateral size remains substantially unchanged along the entire fiber. By substantially unchanged lateral size, it is meant that the diameter may undergo variations that, however, do not exceed 30% of the average measured value.

Fibers with this shape and these sizes have a greater surface/volume ratio than known fibers, which typically have a diameter greater than 100 pm, as well as greater mechanical and structural properties that offer greater efficiency and performance compared to industry standards. The large specific surface of the fibers obtained makes them particularly suitable for the transport and release of active ingredients. The obtained nanofibers allow to have a specific surface between 1 and 30 m²/g, preferably between 2 and 20 m²/g.

These fibers allow to obtain membrane substrates which are typically white in color, or in any case light

The membrane substrate is made of a biocompatible polymer material able to be electrospun selected from xanthan gum, pectins, chitin, chitosan, dextran, carrageenan, guar gum, agar, hydroxypropyl methyl cellulose HPMC, hydroxypropyl cellulose HPC, hydroxyethyl cellulose HEC, sodium carboxymethyl cellulose Na-CMC, albumin, starch, gelatin, collagen, elastin, [3- glucans, chondroitin sulfate, dermatan sulfate, heparin, heparan sulfate, Hyaluronic acid HA, galactomannans, xylans, gum arabic, gum ghatti, glucomannan, acemannan, soluble dietary fibers, glycogen, amylose and polysaccharides derived from plants, bacteria and fungi, and their derivatives. Such compounds or classes of compounds have as their properties the possibility of modifying the viscosity of liquids, which makes them suitable to form regular electrospun fibers with good mechanical and absorption properties. They are also all biocompatible, of natural origin, and can be used in the food, pharmaceutical and/or cosmetic sectors. In particular, xanthan gum, dextran, carrageenan, Na-CMC, starch, gelatin and gum ghatti are used as a thickener, stabilizer and possibly also as a gelling agent in the food sector. In addition, xanthan gum is used as a stabilizer for suspensions and emulsions in the pharmaceutical and cosmetic sectors, guar gum is used as a thickener and gelling agent also in the pharmaceutical and cosmetic sector, carrageenan is used as an inactive excipient in the pharmaceutical sector. Dextran is also used as a thickener in the pharmaceutical sector.

Chitosan is used in the food sector, in low-calorie diets, and in the pharmaceutical sector as an excipient, in particular for products to be inhaled. Pectin, on the other hand, is used as a gelling agent in the food sector and as a dietary and probiotic agent in the pharmaceutical sector.

Agar agar, galactomannans and glucomannan are used as a gelling agent in the nutritional sector. Among cellulose derivatives, HPMC is used as a stabilizer and viscosity regulator in the food sector, and as an eye drop or excipient for oral medicines in the pharmaceutical sector. HPC is used as a food additive, and as an eye drop or tablet binder in the pharmaceutical sector. HEC is used as a thickener and gelling agent in the pharmaceutical and cosmetic sectors. p-glucans are normally used as dietary fibers, as are xylans. Chondroitin sulfate is used as a dietary supplement, and also in the treatment of osteoarthritis symptoms. Dermatan sulfate, heparin and heparan sulfate are known as anticoagulants in the pharmaceutical sector.

Gum arabic is used in the food sector as a stabilizing excipient and viscosity modifier. Acemannan, on the other hand, is known in the pharmaceutical sector for its immunostimulant properties.

It should be noted that some of these compounds have their own functions in the cosmetic, pharmaceutical or food sectors, such as for example starch, elastin, hyaluronic acid, heparin, collagen, pectin, p-glucans, chondroitin sulfate, dermatan sulfate, heparan sulfate and their derivatives, among others. It is therefore advantageous to electrospin these compounds, since the application of the corresponding fibers will allow these compounds to be applied in greater doses than in known solutions, to the advantage of their greater effectiveness.

If the biocompatible polymer material to be electrospun is hyaluronic acid, it can be of the linear or cross-linked type, and can have a high mass, for example of the order of one million Daltons or even more, or alternatively have a low mass, typically of the order of 10000 Daltons or less. It is also possible to provide a mixture of linear hyaluronic acid with cross-linked hyaluronic acid, so as to modulate the stiffness of the yam which will be obtained, as well as the three- dimensional structure of a film obtainable by depositing the yarn on a support.

Also included in the composition of the membrane substrate is at least one electrospinning promoter which is a favorably biocompatible uncharged vector polymer. This is selected from alginate, possibly in the presence of PEO, and pullulan. The spinning promoter is preferably pullulan, since it allows to achieve the best results.

If the alginate is mixed with the PEO, they may be diluted separately in aqueous or aqueous-based solutions, at a concentration comprised between 0.1% and 30% by weight, preferably between 1% and 20% by weight, more preferably between 5% and 15% by weight. The alginate:PEO mixture, if this latter present, is made in weight ratios preferably comprised between 5:1 and 1 :5, more preferably between 2:1 and 1:2. The best electrospinning results were achieved with ratios equal to 1 : 1 by weight. The pullulan can be diluted in aqueous or aqueous-based solution preferably at a concentration comprised between 0.1% to 30% by weight, preferably between 1% and 20% by weight, more preferably between 5% and 15% by weight.

The polymer material to be electrospun and the promoter are mixed in ratios (first compound): promoter preferably comprised between 10: 1 and 1:10, more preferably between 5:1 and 1 :5, even more preferably between 2: 1 and 1 :2 by weight. It was possible to verify that the best results are achievable with compositions in which the weight ratio between first compound and promoter is equal to 1 :1.

The membrane substrate also contains a surfactant, selected from biosurfactants, that is, surfactants of biological and organic origin, as opposed to surfactants of bacterial origin.

In particular, the surfactants of the composition are advantageously obtained by fermentation of gram-positive microorganisms.

More precisely, the biosurfactant is selected from lipopeptides, in particular those originating from the fermentation of organisms of the species Bactillus, more in particular those with low molecular weight, for example whose molecular weight is at most 10000 g/mol, preferably at most 5000 g/mol, more preferably at most 2500 g/mol. Among these lipopeptides are several families, such as Surfactins, Iturins, Fengycins, Kurstatins and Locillomycins. These families of lipopeptides are distinguished from each other by the type and sequence of amino acid residues, the nature of the peptide cycle, and the nature, length, and branching of the fatty acid chain. All, however, have surfactant properties.

Preferably, the biosurfactant of the composition is selected from the family of Surfactins.

In the Surfactin family there are Surfactins themselves, which can be produced through different branches of the Bacillus species, especially B. subtilis, but also others, such as B. natto or B. circulans. Their structure comprises a lactone ring formed by seven amino acids with a characteristic chiral sequence (L-Glu, L-Leu, D-Leu, L-Val, L-Asp, D-Leu and L-Leu in which the first and last amino acid are linked by an ester linkage to form the lactone ring). Surfactins have a chain of P- hydroxy fatty acid with a length of thirteen to sixteen carbon atoms. Although more than 30 congeners are known among Surfactins, they all have the same LLDLLDL chiral sequence of amino acids in the lactone ring. Congeners indicate molecules of the same genus but not isomers.

The family of Surfactins also comprises Pumilacidins, obtainable by means of the B. pumilus branch with variants A-F. Compared to Surfactins, the amino acids in position 7 are substituted with L-Val or L-Ile.

Finally, the family of Surfactins comprises Lichenysins, obtained mainly from B. licheniformis, which differ from Surfactins due to the substitution in position 1 of the lactone ring of L-glutamic acid with L-glutamine.

Surfactins, Pumilacidins and Lichenysins comprise five hydrophobic residues (Leu, Vai or He) and a long secondary aliphatic chain that give them powerful surfactant properties. In fact, it has been verified that a high purity Surfactin family compound is able to lower the surface tension of water from 72 to 27 mN/m at a concentration of 0.0005% by weight. Surfactins are stable and soluble in water over a wide range of pHs (5-13) and temperatures, making them particularly suitable to be electrospun in aqueous solutions.

Preferably, the biosurfactant is a surfactin or biosurfactin.

Generally, the biosurfactant is present at a concentration of less than 5%, preferably less than 2%, more preferably comprised between 0.5% and 1% by weight on the weight of the composition.

Preferably, the composition also comprises at least one active ingredient, of the pharmaceutical, nutritional and/or cosmetic type.

It should be noted that the active ingredients can have various types of functions, regardless of their field of action.

The cosmetic active ingredient can be of the following types: anti-seborrheic (e.g. sebacic acid, azelaic acid), anti-sebum (e.g. coal dust), antimicrobial (for example climbazole, pyroctone olamine), antioxidant (e.g. ascorbic acid, tocopherol, co-enzyme Q10, resveratrol, glutathione), antiperspirant (e.g. aluminium chlorohydrate, aluminium sesquichloro hydrate), astringent (e.g. Citrus aurantifolia flower extract, calcium lactate), bleaching (e.g. glabridin, ammonium persulphate), make-up remover (e.g. sodium cocoyl glutamate), deodorant (e.g. triethyl citrate, zinc ricinoleate), exfoliant (e.g. glycolic acid, malic acid, mandelic acid), flavorings (e.g. citral, honey), fragrance (e.g. d, 1-limonene, coumarin), humectant (e.g. glycerin, propanediol), keratolytic (e.g. chloroacetic acid, salicylic acid), moisturizer (e.g. Aloe arborescens leaf extract), fragrant (e.g. geraniol, linalool), emollient (e.g. triolein, squalene), refreshing (e.g. menthol, menthyl lactate), skin moisturizer (e.g. panthenol, allantoin), skin protection (e.g. sphingolipids, zinc oxide), smoothing (e.g. Ricinus communis seed oil), soothing (e.g. extracts of Hamamelis virginiana, extracts of Chamomile Retrotic, bisabolol) or tonic (e.g. arnica montana, Capsicum frutescens extract), UV filter (for example methylene bis-benzotriazolyl tetramethylbutylphenol, ethylhexyl methoxycinnamate, caffeine, theine, theobromine, theophylline), anti-wrinkles (e.g. aminobutyric acid), one or more peptides and their metabolites and derivatives (e.g. essential and branched amino acids, tetrapeptides).

The pharmaceutical active ingredient can be of the following types: 5-alpha- reductase inhibitor (e.g. finasteride), 5-aminosalicylates (e.g. mesalamine), 5HT3 receptor antagonist (e.g. ondansetron), ACE inhibitor with calcium channel blocker (e.g. amlodipine/benazepril), ACE inhibitor with thiazide (e.g. hydrochlorothiazide), adamantane antivirals (e.g. amantadine), adrenal corticosteroid inhibitor (e.g. aminoglutethimide), adrenergic bronchodilator (e.g. albuterol), agent for hypertensive emergencies (e.g. diazoxide), pulmonary hypertension agent (e.g. treprostinil), aldosterone receptor antagonist (e.g. spironolactone), alkylating agent (e.g. cyclophosphamide), allergens (e.g. house dust mite allergen extracts), alpha-glucosidase inhibitor (e.g. miglitol), amebicides (e.g. metronidazole), aminoglycosides (e.g. tobramycin), aminopenicillins (e.g. amoxicillin), amino salicylates (e.g. amino salicylic acid), AMPA receptor antagonist (e.g. perampanel), amylin analogues (e.g. pramlintida), analgesics (e.g. acetaminophen), androgenic and anabolic steroids (e.g. testosterone), angiotensin converting enzyme inhibitor (e.g. ramipril), angiotensin II inhibitor with calcium channel blocker (e.g. amlodipine/olmesartan), angiotensin II inhibitor with thiazides (e.g. hydrochlorothiazide/olmesartan), angiotensin receptor blockers (e.g. valsartan), angiotensin receptor blocker and neprilysin inhibitor (e.g. sacubitril/valsartan), anorectal preparations (e.g. hydrocortisone/pramoxin), anorectics (e.g. phentermine), antacids (e.g. magnesium hydroxide), anthelmintics (e.g. pyrantel), anti-angiogenic ophthalmic agents (e.g. aflibercept), anti-CTLA-4 monoclonal antibody (e.g. ipilimumab), anti-PD-1 monoclonal antibody (e.g. nivolumab), anti-adrenergic agent (central) with thiazides (e.g. hydrochlorothiazide/methyldopa), anti-adrenergic agent (peripheral) with thiazides (e.g. polythiazide/prazosin), centrally acting anti- adrenergic agent (e.g. guanfacine), anti-adrenergic agent, peripherally acting (e.g. tamsulosin), antiandrogens (e.g. enzalutamide), antianginal agent (e.g. nitroglycerin, dyphyllin/guaifenesin), antibiotics (e.g. metronidazole), antibiotics/antineoplastics (e.g. doxorubicin), anticholinergic antiemetics (e.g. diphenhydramine), anticholinergic antiparkinsonian agent (e.g. procyclidine), anticholinergic bronchodilators (e.g. thiotropin), for example anticholinergic/antispasmodic (e.g. hyoscyamine), anticoagulant agent (e.g. phytonadione), anticonvulsant (e.g. lacosamide), antidepressant (e.g. bupropion), antidiarrheal (e.g. loperamide), antidiuretic hormone (e.g. desmopressin), antidote (e.g. naltrexone dronabinol), antifungal (e.g. griseofulvin), antigonadotropic agent (e.g. danazol), antigout agent (e.g. colchicine), antihistamine (e.g. cetirizine), anti-hyperlipidemic agent and combinations (e.g. ezetimibe/simvastatin), antihyperuricemic agent (e.g. febuxostat), antimalarial (e.g. doxycycline), antimalarial combination, antimalarial quinoline (e.g. hydroxychloroquine), antimanic agent (e.g. lithium), antimetabolite (e.g. capecitabine), antimigraine agent (e.g. rizatriptan), antineoplastic (e.g. isotretinoin), antineoplastic combination (e.g. letrozole/ribociclib), antineoplastic detoxifying agent (e.g. amifostine), antineoplastic interferon (e.g. interferon alfa- 2b), antipseudomonal penicillin (e.g. carbenicillin), antipsoriatic (e.g. acitretin), antipsychotic agent (e.g. haloperidol), antirheumatic (e.g. adalimumab), antiseptic and germicide, antithyroid agent (e.g. potassium iodide), antitoxin and antiviral (e.g. antivenin (Crotalidae) polyvalent), antitussive (e.g. dextromethorphan), antiviral booster (e.g. ritonavir), antiviral interferon (e.g. peginterferon alfa-2a), aromatase inhibitor (e.g. anastrozole)), atypical antipsychotic (e.g. aripiprazole), azole antifungal (e.g. fluconazole), bacterial vaccine (e.g. 13-val ent pneumococcal vaccine), barbiturate anticonvulsant (e.g. primidone), barbiturate (e.g. phenobarbital), BCR- tyrosine kinase inhibitor ABL (e.g. imatin), benzodiazepine anticonvulsant (e.g. diazepam), benzodiazepine (e.g. clonazepam), beta blocker with thiazides (e.g. bisoprolol/hydrochlorothiazide), beta-lactamase inhibitor (e.g. clavulanic acid), bile acid sequestrant (e.g. colesevelam), bisphosphonate (e.g. zoledronic acid), BTK inhibitor (e.g. ibrutinib), calcimimetic (e.g. cinacalcet), calcineurin inhibitor (e.g. tacrolimus), calcitonin, calcium channel blocker (e.g. verapamil), carbamate anticonvulsant (e.g. felbamate), carbapenem (e.g. doripenem), carbapenem/beta-lactamase inhibitor (e.g. meropenem/vaborbactam), carbonic anhydrase inhibitor anticonvulsant (e.g. topiramate), carbonic anhydrase inhibitor (e.g. acetazolamide), regenosadase stressor, cardio selective beta- blockers (e.g. nebivolol), catecholamines (e.g. epinephrine), monoclonal antibody CD20 (e.g. ocrelizumab), monoclonal antibody CD30 (e.g. brentuximab), monoclonal antibody CD33 (e.g. gemtuzumab), monoclonal antibody CD38 (e.g. monoclonal CD52, alemtuzumab), CDK 4/6 inhibitor (e.g. palbociclib), cephalosporin/beta-lactamase inhibitor (e.g. avibactam/ceftazidime), cerumenolytics (e.g. carbamide peroxide), CFTR combination (ivacaftor/lumacaftor), CFTR enhancer (e.g. ivacaftor), CGRP inhibitor (e.g. erenumab), chelating agent (e.g. deferasirox), chemokine receptor antagonist (e.g. maraviroc), chloride channel activator (e.g. lubiprostone), cholesterol absorption inhibitor (e.g. ezetimibe), cholinergic agonist (e.g. cevimeline), cholinergic muscle stimulant (e.g. pyridostigmine), cholinesterase inhibitor (e.g. donepezil), central nervous system stimulant (e.g. phentermine), colony-stimulating factor (e.g. filgrastim), contraceptive (e.g. levonorgestrel), corticotropin, coumarins and indandions (e.g. warfarin), cox-2 inhibitor (e.g. celecoxib), decongestant (e.g. pseudoephedrine), diarylquinolines, benzodiazepine anticonvulsant (e.g. carbamazepine), digestive enzyme (e.g. lactase), dipeptidyl peptidase 4 inhibitor (e.g. sitagliptin), dopaminergic antiparkinsonian agent (e.g. ropinirole), drug used in alcohol dependence (e.g. acamprosate), echinocandins (e.g. caspofungin) inhibitor (e.g. erlotinib), estrogen receptor antagonist (e.g. fulvestrant), estrogen (e.g. estradiol), expectorant (e.g. guaifenesin), factor Xa inhibitor (e.g. rivaroxaban), drug-derived anticonvulsant fatty acids (e.g. divalproex sodium), fibric acid derivative (e.g. fenofibrate), 1st generation cephalosporins (e.g. cephalexin), 4th generation cephalosporins (e.g. cefepime), gallstone solubilizing agent (e.g. ursodiol), gamma-aminobutyric acid analogue (e.g. gabapentin), gamma-aminobutyric acid reuptake inhibitor (e.g. tiagabine), general anesthetic (e.g. propofol), GI stimulant (e.g. metoclopramide), glucocorticoids (e.g. budesonide), glucose-elevating agent (e.g. glucagon), glycopeptide antibiotic (e.g. vancomycin), platelet glycoprotein inhibitor (e.g. tirofiban), glycylcycline (e.g. tigecycline), gonadotropin-releasing hormone (e.g. leuprolide), gonadotropinreleasing hormone antagonist (e.g. elagolix), gonadotropin (e.g. chorionic gonadotropin), group I antiarrhythmic (e.g. phenytoin), group II antiarrhythmic (e.g. propranolol), group III antiarrhythmic (e.g. dronedarone), group IV antiarrhythmic (e.g. verapamil), group V antiarrhythmic (e.g. digoxin), growth hormone receptor blocker (e.g. pegvisomant), growth hormone (e.g. somatropin), guanylate cyclase-C agonist (e.g. linaclotide), H. pylori eradication agent (e.g. bismuth subcitrate potassium/metronidazole/tetracyclines), H2 antagonist (e.g. ranitidine), hedgehog pathway inhibitor (e.g. vismodegib), heparin antagonist (e.g. protamine), HER2 inhibitor (e.g. neratinib), herbal product (e.g. neratinib). 5- hydroxytryptophan, aloe vera), histone deacetylase inhibitor (e.g. romidepsin), hormone/antineoplastic (e.g. medroxyprogesterone), hydantoin anticonvulsant (e.g. phenytoin), hydrazide derivative (e.g. isoniazid), immunoglobulin, impotence agent (e.g. sildenafil), incretin mimetic (e.g. liraglutide), inotropic agent (e.g. digoxin), insulin and derivatives (e.g. insulin glargine), insulin-like growth factor (e.g. mecasermin), interferon (e.g. interferon beta- la), interleukin inhibitor (e.g. dupilumab), interleukin (e.g. aldesleukin), iron product (e.g. ferrous sulfate), ketolide (e.g. telithromycin), laxative (e.g. bisacodyl), leprostatic (e.g. clofazimine), leukotriene modifier (e.g. montelukast), lincomycin derivative (e.g. clindamycin), loop diuretic (e.g. furosemide), lysosomal enzyme (e.g. imiglucerase), macrolide (e.g. azithromycin), mast cell stabilizer (e.g. cromolyn), meglitinide (e.g. repaglinide), melanocortin receptor agonist (e.g. bremelanotide), methylxanthine (e.g. theocortic), mineral corticoid (e.g. fludrocortisone), mineral and electrolyte (e.g. citric acid/potassium citrate), various antivirals (e.g. baloxavir marboxil), various anxiolytics, sedatives and hypnotics (e.g. zolpidem), various bone resorption inhibitors (e.g. denosumab), various cardiovascular agents (e.g. midodrine), various central nervous system agents (e.g. dalfampridine), various coagulation modifiers (e.g. tranexamic acid), various diuretics (e.g. pamabrom), various genitourinary tract agents (e.g. phenazopyridine), various gastrointestinal agents (e.g. misoprostol), various metabolic agents (e.g. burosumab), various respiratory agents (e.g. alpha 1 -proteinase inhibitor), various topical agents (e.g. sodium hyaluronate), various vaginal agents (e.g. estradiol), mitotic inhibitor (e.g. vincristine), monoamine oxidase inhibitor (e.g. phenelzine), mouth and throat product (e.g. fluoride), mTOR inhibitor (e.g. everolimus), mucolytic (e.g. acetylcysteine), multikinase inhibitor (e.g. sorafenib), combination narcotic analgesic (e.g. buprenorphine/naloxone), narcotic analgesic (e.g. fentanyl), natural penicillin (e.g. penicillin v potassium), neuraminidase inhibitor (e.g. oseltamivir), neuronal potassium channel opener (e.g. ezogabine), new generation cephalosporins (e.g. ceftaroline), NHE3 inhibitor (e.g. ceftaroline), nicotinic acid (e.g. ethionamide), NK1 receptor antagonist (e.g. aprepitant), NNRTIs (e.g. efavirenz), non-cardioselective beta blocker (e.g. carvedilol), non-sulfonylureas (e.g. metformin), nonsteroidal anti-inflammatory drug (e.g. diclofenac), NS5A inhibitor (e.g. daclatasvir), nucleoside reverse transcriptase inhibitor (NRTI) (e.g. tenofovir), nutraceutical product (e.g. omega-3 polyunsaturated fatty acids), oral dietary supplement (e.g. arginine), other immunostimulants (e.g. glatiramer), other immunosuppressants (e.g. omalizumab), oxazolidinedione anticonvulsant (e.g. trimethadione), oxazolidinone antibiotic (e.g. linezolid), PTH and analogues (e.g. teriparatide), PARP inhibitor (e.g. niraparib), PCSK9 inhibitor (e.g. evolocumab), penicillinase resistant penicillin (e.g. oxacillin), peripheral opioid receptor antagonist (e.g. naloxegol), mixed peripheral opioid receptor agonists (agonist/antagonist eluxadoline), peripheral vasodilator (e.g. isoxsuprine), peripherally acting anti-obesity agent (e.g. orlistat), phenothiazine antiemetic (e.g. promethazine), phenothiazine antipsychotic (e.g, prochlorperazine), phenylpiperazine antidepressant (e.g. trazodone), potassium phosphate inhibitor (e.g. trazoderrone, idelalisib), platelet aggregation inhibitor (e.g. aspirin), platelet stimulating agent (e.g. eltrombopag), polyene (e.g. nystatin), potassium-sparing diuretic (e.g. spironolactone), probiotic (e.g. lactobacillus acidophilus), modulator receptor inhibitor (e.g. ulipristal), progestogen levonorgestrel), prolactin inhibitor (e.g. cabergoline), protease inhibitor (e.g. telaprevir), protease-activated receptor- 1 antagonist (e.g. vorapaxar), proteasome inhibitor (e.g. for example bortezomib), proton pump inhibitor (e.g. omeprazole), psoralens (e.g. methoxsalen), purine nucleoside (e.g. valaciclovir), pyrrolidine anticonvulsant (e.g. levetiracetam), quinolones (e.g. ciprofloxacin), recombinant human erythropoietin (e.g. epoetin alfa), renin inhibitor (e.g. aliskiren), rifamycin derivative (e.g. rifampicin), salicylate (e.g. aspirin), second generation cephalosporin (e.g. selective cefuroxime receptor), modulator (e.g. ospemifene), selective immunosuppressant (e.g. natalizumab), selective phosphodiesterase-4 inhibitor (e.g. roflumilast), selective serotonin reuptake inhibitor (e.g. escitalopram), serotoninnorepinephrine reuptake inhibitor (e.g. duloxetine), serotoninergic neuroenteric modulators (e.g. tegaserod), SGLT-2 inhibitor (e.g. empagliflozin), skeletal muscle relaxant (e.g. onabotulinumtoxinA), smoking cessation agent (e.g. nicotine analogue somatostat, octreotide), statin (e.g. lovastatin), streptogramin (e.g. dalfopristin/quinupristin), streptomyces derivative (e.g. capreomycin), anticonvulsant succinimide (e.g. ethosuximide), sulfonamide (e.g. sulfamethoxazole), sulphonylurea stimulant (e.g. glimepistole, clomiphene), tetracyclic antidepressant (e.g. mirtazapine), tetracyclines (e.g. minocycline), thiazide diuretics (e.g. hydrochlorothiazide), thiazolidinedione (e.g. pioglitazone), thioxanthene (e.g. thiothixene), third generation cephalosporin (e.g. ceftriaxone), thrombin inhibitor (e.g. dabigatazone), streptolytic (e.g. levothyroxine), TNF alpha inhibitor (e.g. adalimumab), tocolytic agent (e.g. terbutaline), topical acne agent (e.g. tretinoin), topical anesthetic (e.g. lidocaine), topical anti-infective (e.g. malathion), topical anti-rosacea agent (e.g. ivermectin), topical antibiotic (e.g. silver sulfadiazine), topical antifungal (e.g. econazole), topical antihistamine (e.g. diphenhydramine), topical antineoplastic (e.g. imiquimod), topical anti-psoriatic (e.g. tazarotene), topical antivirals (e.g. penciclovir), topical astringent (e.g. hazelnut), topical debridement agent (e.g. collagenase), topical depigmenting agent (e.g. hydroquinone), topical emollient (e.g. emollients), topical keratolytics (e.g. salicylic acid), topical non-steroidal anti-inflammatory (e.g. diclofenac), topical photochemistry (e.g. aminolevulinic acid), topical rubefacient (e.g. menthol), topical steroid (e.g. betamethasone), topical steroid with anti-infectives (e.g. acyclovir/hydrocortisone), transthyretin stabilizer (e.g. tafamidis), triazine anticonvulsant (e.g. lamotrigine), tricyclic antidepressant (e.g. amitriptyline), urea cycle disruptor (e.g. sodium phenylbutyrate), urinary anti-infective (e.g. nitrofurantoin), urinary antispasmodic (e.g. amitriptyline) modifier (e.g. potassium citrate), uterotonic agent (e.g. dinoprostone), vaginal anti-infective (e.g. clindamycin), vasodilator (e.g. alprostadil), vasopressin antagonist (e.g. conivaptan), vasopressor (e.g. epinephrine), VEGF/VEGFR inhibitor (e.g. pazopan), viral vaccine, vitamin and mineral combination, vitamin (e.g. cyanocobalamin), VMAT2 inhibitor (e.g. valbenazine). The nutritional active ingredient can be of the following types: vitamin (e.g. vitamins A, B, C, D, E, K, folic acid, biotin), mineral (e.g. potassium, chlorine, sodium, calcium, phosphorus, magnesium, iron, zinc, manganese, copper, iodine, chromium, molybdenum, selenium, cobalt, fluoride), amino acid, peptide and protein and their metabolites and derivatives (e.g. essential and branched-chain amino acids, carnosine, enzymes and enzyme complexes, lactoferrin, N- acetylcysteine, proteins of animal or plant foods), fatty acid (e.g. omega-3, omega- 6, omega-9 fatty acids), natural product manufactured using intact sources or substances extracted or derived from plants, animals, algae, fungi, lichens or bacteria (e.g. phytosterol, echinacea, green tea extract, garlic, aloe vera, fish oil, spirulina, chlorella, digestive enzymes derived from mushrooms), sugar and polysaccharide (e.g. mannose, ribose, trehalose, dextrose, glucuronolactone, dextrin), probiotic (e.g. live microorganisms such as Lactobacillus spp, Bifidobacterium spp, Sacc boulardii), prebiotic (e.g. fructans, such as fructooligosaccharides and inulins, galactans, such as galactooligosaccharides and xylooligosaccharides), antioxidant (e.g. lipoic acid, coenzyme Q10, flavonoids, glutathione, resveratrol, catechins), other substances with a nutritional or physiological effect (e.g. betaine, caffeine theobromine, theophylline, CDP- choline, choline, creatine, phospholipids, GABA, glucosamine, inositol, melatonin, methylsulfonylmethane, nucleotides, squalene).

The inclusion of the active ingredient in the electrospun fiber can be obtained by co-electrospinning the active ingredient with the biocompatible polymer material, the promoter and the surfactant, if present. In this case, a mixture of polymer material to be electrospun and the electrospinning promoter with the active ingredient can be prepared, possibly also in the presence of the surfactant, and the mixture obtained is electrospun.

Alternatively, it can be provided to electrospin the biocompatible polymer material, the promoter and the surfactant at first, and subsequently to integrate the active ingredient into the fiber obtained. Depending on applications, it can be provided that the active ingredient is absorbed into the electrospun fiber, or that it is trapped in the three-dimensional structure obtained with the electrospun fiber.

For example, the polymer material to be electrospun can comprise a mixture of linear hyaluronic acid with cross-linked hyaluronic acid. The cross-linked hyaluronic acid has the effect of increasing the stiffness of the nanometric fibers obtained, but also of increasing the complexity of the three-dimensional structure of a film obtained by means of the continuous deposit of the fibers obtained on multiple layers. In particular, the presence of cross-linked hyaluronic acid causes the formation of cavities in the film, cavities that allow to house the active ingredient molecules.

According to another example, the active ingredient is a non-steroidal antiinflammatory, to be applied for example on a skin burn. It can also be provided to add, as additional active ingredients, one or more analgesics to soothe the pain caused by the burn. For this type of application, it is particularly advantageous that the biocompatible polymer material is of the type that is regenerating for the skin, such as hyaluronic acid.

The article according to the invention can be advantageously used in the treatment of skin bums. It is advantageous because it results in rapid absorption of the active ingredient and also of the first compound into the wound. Moreover, the product obtainable by electrospinning the composition can be applied directly on the burnt area. This improves the effectiveness of the treatment.

Advantageously, the active ingredient is present at a concentration comprised between 0.1% and 30% by weight, more preferably between 0.2% and 20% by weight, even more preferably between 0.5% and 10% by weight.

Please note that hyaluronic acid, as a compound to be electrospun, is a good candidate to be combined with several active ingredients, of each of the three types indicated above. For example, among cosmetic active ingredients, the following can be mentioned: anti-seborrheic (sebacic acid, azelaic acid), antioxidants (ascorbic acid, tocopherol, retinol, retinal), anti-stain (glabridin, ammonium persulfate), emollients (extract of Hamamelis virginiana, bisabolol) and humectants (e.g. glycerin, propanediol), anti-wrinkles (e.g. aminobutyric acid) and the one or more peptides and their metabolites and derivatives (e.g. essential and branched amino acids, tetrapeptides).

Among the preferred nutritional active ingredients are natural products manufactured using intact sources or substances extracted or derived from plants, animals, algae, fungi, lichens or bacteria (phytosterol, echinacea, green tea extract, garlic, aloe vera, fish oil, spirulina, chlorella, fungal-derived digestive enzymes), vitamins (e.g. vitamins A, B, C, D, E, K, folic acid, biotin) and antioxidants (e.g. lipoic acid, coenzyme Q10, flavonoids, glutathione, resveratrol, catechins).

The most advantageous pharmaceutical active ingredients are androgens and anabolic steroids (e.g. testosterone), anti-CTLA-4 monoclonal antibodies (e.g. ipilimumab), anti-PD-1 monoclonal antibodies (e.g. nivolumab), antianginal agents (e.g. nitroglycerin), anti-asthmatic combinations (e.g. diphylline/guaifenesin), antibiotics (e.g. metronidazole), antibiotics/antineoplastics (e.g. doxorubicin), antineoplastics (e.g. isotretinoin) and antineoplastic combinations (e.g. letrozole/ribociclib). An example of a patch product comprises a membrane substrate composed of an electrospun fiber obtained from a composition comprising sodium hyaluronate, as a source of hyaluronic acid, together with pullulan serving as an electrospinning promoter, as well as mannitol, sodium surfactine as a surfactant, aminobutyric acid, acetyl tetrapeptide-9 and acetyl tetrapeptide- 11. Such a patch product is particularly suitable for application on the skin of the face, in particular to rejuvenate the skin.

Please note that such active ingredients may advantageously be combined with other compounds to be electrospun such as, for example, xanthan gum, guar gum, chondroitin sulfate, collagen or starch.

Another example of a patch product is based on heparin as a compound to electrospin and a pharmaceutical active ingredient, for example an allergen extract or a platelet stimulating agent, such as eltrombopag. According to some embodiments, the patch product also comprises a stabilizer, which is preferably a cross-linkable polymer. An example of a stabilizer is sodium alginate, which should be added to pullulan as a promoter. Preferably, the ratio of pullulan: alginate is comprised between 3:1.5 and 3:0.5, more preferably it is 3:1.

Once the article is made, it can be closed by applying a covering sheet on the base support. The covering sheet is attached to the base support, for example by gluing or welding. The sheet can be of the same material as the base support, or it can be made with another polysaccharide or another starch, or it can be made of materials already known in the field, such as for example poly butylene succinate adipate PBSA or polylactic acid PLA. It can also be provided to package the article, that is, the membrane substrate and base support assembly, in a sachet of a known type made for example with two sheets of heat-sealable material, such as PBSA or PLA, reciprocally welded so as to form a hermetically sealed internal space, in which the article is enclosed.

The article can be packaged in secondary packagings, for example boxes, which contain a plurality of sachets each enclosing a respective article as described above.

The use of the article provides, in a preliminary step, to humidify the area of the skin on which the product should be applied. The sachet is then opened, and the patch product is removed, taking care to only touch the polysaccharide support in order to avoid damaging the membrane substrate, and then the patch product is applied on the humidified area of the skin, with the membrane substrate in direct contact with the skin. Because of the hydrating effect given by the polysaccharide support, which combines with the hydrating effect of the membrane substrate, and the adaptability of the shape of the support, the membrane substrate is quickly and totally absorbed into the skin. The support is kept on the skin for a few seconds, the amount of time for the absorption of the membrane substrate to be completed, and then it is removed. Please note that in this period of time, even if short, the polysaccharide support produces a hydrating effect on the skin.

EXAMPLES An evaluation was carried out on thirty volunteers, who were asked to apply a cosmetic patch product of an article according to the invention, and a placebo.

Each volunteer applied both the cosmetic product and also the placebo, each on a respective arm, in particular on the palm area of the forearm, at the rate of one application per day for a period of four months.

The cosmetic product and the placebo were supplied in the form of sheets of electrospun fibers, approximately 10cm² in size, on a non-genetically modified corn starch base support with a high amylose content.

The cosmetic product used comprises Hyaluronic acid HA as a biocompatible polymer material to be electrospun and pullulan as an electrospinning promoter.

The electrospun solution was prepared by dissolving 25g of hyaluronic acid, 12.5g of pullulan and 1g of biosurfactin in 30-50mL of water, and bringing the volume to lOOmL for dilution, controlling the pH and possibly correcting it by adding a IM NaOH solution so as to obtain a pH of 5.5-6. The placebo, on the other hand, contains only pullulan, without hyaluronic acid.

Similarly to what indicated for the cosmetic product, 15g of pullulan are dissolved in 30-50 mL of water, and brought to lOOmL for dilution, controlling the pH and possibly correcting it by adding a IM NaOH solution so as to obtain a pH of 5.5- 6. The solution obtained was then electrospun. The effects of the treatment were measured through instrumental methods, in particular to assess skin hydration, skin elasticity and collagen density. Measurements were performed before the start of the treatment (TO), and after 1 (Tl), 2 (T2) and 3 months (T3) of treatment.

Evaluation of skin hydration Skin hydration was measured with a Derma Unit SSC 3 device from

Courage+Khazaka, to which a Corneometer® hydration probe was added. The probe is constructed with a series of golden metal tracks to function as plates of a capacitor. The plates are electrically insulated by an electrical insulator, called dielectric. After connection to an electric power supply, electrons flow between the plates creating an electric field: the amount of charge stored by the capacitor is called capacitance. Most materials have a dielectric constant greater than the vacuum, so that any material between the capacitor plates will increase the capacitance. The water present in the skin causes a variation in the capacitance proportional to its content, giving a measure of skin hydration in arbitrary units.

Evaluation of skin elasticity

The measurement of skin elasticity was performed with a DermaLab Combo Skinlab elasticity probe, from the company Cortex. The probe is equipped with a chamber in which a vacuum is applied, and which allows suction to be applied on the surface of the skin. The suction method includes a skin elevation step and a skin retraction step, which are controlled by infrared sensors in the probe chamber. One of the parameters related to skin elasticity is Retraction Time, which represents the time expressed in milliseconds that is necessary for the skin to retract by 1.5 mm after it has been taken to the point of maximum elevation. Young, elastic skin quickly returns to its initial state when it is elevated, while less elastic skin will have longer retraction times. Therefore, a reduction in retraction time is an indication of an increase in skin elasticity.

Evaluation of collagen density High-resolution images of deeper layers of the skin were obtained using a DermaLab Combo Skinlab ultrasonic probe (Cortex). The technique is based on measuring the acoustic response of the skin, when an acoustic pulse at a known frequency is sent to the skin itself. This acoustic pulse hits the different structures of the skin and is partly reflected. The part of the signal that is reflected is picked up by an ultrasound transducer and processed in order to provide a cross-section image of the skin. The intensity of the reflected signal is indicated with a color scale, in which the darkest zones represent the zones with low response (those in which the density of the structures is low or not), while the lighter areas represent the areas with higher density. This technique allows to reconstruct the image of the skin up to a depth of 3.4 mm with a resolution of 0.06 mm, highlighting the structure of the epidermis, dermis and subcutaneous layer. An image processing software provides a value of the intensity of the echogenic response that is directly correlated to the density of the collagen. The energy of the acoustic pulses used is very low and has no negative effect on the skin and other tissues. Analyses

The measurements were carried out in a temperature-controlled environment, at 21 ± 2°C, and with a humidity of approximately 50%. Volunteers were acclimatized for 15 minutes before each measurement. The application of the cosmetic product and the placebo provides to humidify the skin in correspondence with the area to be treated, apply the product sheet with the base support facing upward, leave the product to humidify so that it adheres well to the skin, remove the base support, and possibly lightly tap the treated area so that the product is completely absorbed, if necessary.

Results

The results of the treatments in terms of skin hydration are summarized in Table

1 below and in the graphs of fig. 1. The skin hydration measurements, expressed in arbitrary comeometry units, are reported as the average value of the values recorded during the test, as the difference and percentage variation between the initial values (TO) and the values recorded after 1 month (Tl), 2 months (T2) and 3 months (T3). An area of the skin that was not treated (with either cosmetic or placebo) was arbitrarily determined as a control zone.

Cosmetic product Placebo Control

The treatment with the cosmetic product showed a significant increase in skin hydration after 1, 2 and 3 months, equal to 6.8%, 18.9% and 17.9% respectively. No significant change was observed with the placebo and in the control zone.

The results in terms of skin elasticity are summarized in Table 2, and represented in the graphs of fig. 2. The elasticity data, expressed in milliseconds (msec), are reported as the average value of the values recorded during the test, as the difference and percentage variation between the initial values (TO) and the values recorded after 1 month (Tl), 2 months (T2) and 3 months (T3). An area of the skin that was not treated (with either cosmetic or placebo) was arbitrarily determined as a control zone.

Cosmetic Product Placebo Control

For the treatment with the cosmetic product, a slight but significant increase in skin elasticity was found after 2 and 3 months, equal to 3.7% and 3.8% respectively. An increase was also found after 1 month; however, this is not significant. No significant increase in skin elasticity was observed with the placebo and in the control zone.

The results in terms of collagen density are summarized in Table 3 and in the graphs of fig. 3. The collagen density data are reported as the average value of the values recorded during the test, as the difference and percentage variation between the initial values (TO) and the values recorded after 1 month (Tl), 2 months (T2) and 3 months (T3). An area of the skin that was not treated (with either cosmetic or placebo) was arbitrarily determined as a control zone.

Cosmetic Product Placebo Control T3 60.1 ± 3.9 47.4 ± 3.8 46.6 ± 3.5

The treatment with the cosmetic product allowed to find a significant increase in collagen density after 1, 2 and 3 months, equal to 18.4%, 29.1% and 32.4% respectively. No significant increase in skin elasticity was observed with the placebo and in the control zone.

Another study was conducted to evaluate the effect of the cosmetic product on collagen density. The application modes of the cosmetic product were the same as those indicated above, but the treatment was done over 8 weeks. Figs. 4 and 5 represent a cross-section image of the skin of one of the volunteers, processed starting from the data collected by the instrument used, indicated above. The white zones indicate the presence of collagen.

Fig. 4 shows the section of an area of skin treated with the cosmetic product, at the beginning of the treatment (TO, left) and after 1 month (Tl), 2 months (T2) and 3 months (T3) of treatment. Fig. 5 instead shows an area of skin treated with the placebo, at the beginning of the treatment (TO, left) and after 1 month (Tl), 2 months (T2) and 3 months (T3) of treatment.

In the area treated with the cosmetic product, there is visually an increase in collagen in the skin at the end of the treatment, this increase not being found in the untreated area. In conclusion, on the basis of the tests reported above, it was found that the application of the cosmetic product over continuous periods of 3 months allows to significantly increase the hydration of the skin for the first two months of application by up to 18.9%, with clearly visible results already after 1 month of application; it allows to slightly, yet significantly, increase the elasticity of the skin after 2 and 3 months by up to 3.7% and 3.8%; and to progressively and significantly increase collagen density by up to 32.4%, with evidence of effectiveness already from the first month of application.

It is clear that modifications and/or additions of parts may be made to the article and to the method as described heretofore, without departing from the field and scope of the present invention, as defined by the claims. It is also clear that, although the present invention has been described with reference to some specific examples, a person of skill in the art will be able to achieve other equivalent forms of article containing a patch product and corresponding production method, having the characteristics as set forth in the claims and hence all coming within the field of protection defined thereby. In the following claims, the sole purpose of the references in brackets is to facilitate their reading and they must not be considered as restrictive factors with regard to the field of protection defined by the same claims.

Claims

1. Article comprising a patch product disposed on a base support, wherein said patch product contains a membrane substrate absorbable by the skin formed by at least one electrospun fiber composed of a first compound to be electrospun and an electrospinning promoter, characterized in that said base support comprises a polysaccharide-based biodegradable film not absorbable by the skin.

2. Article as in claim 1, characterized in that said film not absorbable by the skin is starch-based, in particular com starch-based.

3. Article as in claim 1 or 2, characterized in that said starch has an amylose concentration greater than 50% by weight on the weight of the starch.

4. Article as in any claim hereinbefore, characterized in that said film has a thickness of less than 1mm.

5. Article as in any claim hereinbefore, characterized in that said first compound to be electrospun is selected from xanthan gum, pectin, chitin, chitosan, dextran, carrageenan, guar gum, agar, cellulose derivatives, albumin, starch, gelatin, collagen, elastin, P-glucans, glycosaminoglycans, mucopolysaccharides, water- soluble polysaccharides and their derivatives.

6. Article as in claim 5, characterized in that said electrospun compound is selected from starch, elastin, hyaluronic acid, heparin, collagen, pectin, P-glucans, chondroitin sulfate, dermatan sulfate, heparan sulfate and their derivatives.

7. Article as in any claim hereinbefore, characterized in that said electrospinning promoter is selected from alginate, pullulan and a mixture thereof.

8. Article as in any claim hereinbefore, characterized in that said membrane substrate also comprises, as a surfactant, a lipopeptide obtained from Bacillus sp.

9. Article as in claim 8, characterized in that said surfactant is selected from

Surfactins, Pumilacidins and Lichenysins.

10. Article as in any claim hereinbefore, characterized in that said membrane substrate also comprises one or more active ingredients selected from peptides and their metabolites and derivatives.

11. Article as in claim 10, characterized in that said one or more active ingredients are selected from tetrapeptides, in particular from acetyl tetrapeptides.

12. Article as in claim 11, characterized in that said one or more active ingredients are selected from acetyl tetrapeptide-9, acetyl tetrapeptide- 11 and a mixture thereof.

13. Method for producing an article comprising a patch product disposed on a base support, comprising a step of electrospinning a composition comprising a first compound to be electrospun and an electrospinning promoter in order to obtain an electrospun fiber, wherein said electrospun fiber is directly deposited on said base support, characterized in that said base support comprises a polysaccharide- based film not absorbable by the skin.

14. Method as in claim 13, characterized in that said film not absorbable by the skin is starch-based, in particular corn starch-based.

15. Method as in claim 14, characterized in that said starch has an amylose concentration greater than 50% by weight on the weight of the starch.

16. Method as in claim 13, 14 or 15, characterized in that said film has a thickness of less than 1mm.

17. Primary packaging comprising a hermetically closed sachet containing inside it an article as in any claim from 1 to 12.

18. Primary packaging as in claim 17, characterized in that said sachet is composed of two sheets of heat-sealable material reciprocally joined by welding.

19. Secondary packaging comprising a box which contains inside it a plurality of primary packagings as in claim 17 or 16.