Articles including natural polymer-based patch products and methods of making same

Abstract

The present invention relates to an article comprising a patch product comprising a skin-absorbable membrane substrate disposed on a base support and formed by at least one electrospun fiber comprised of an electrospun first compound and an electrospinning enhancer.

Description

[Technical Field]

[0001] The present invention relates to an article containing a product. More particularly, the present invention relates to a patch product in which fibers, in particular nanofibers, preferably obtained by electrospinning, based on a skin-absorbable, biocompatible polymeric compound are deposited on a support and packaged. The support is also based on a biocompatible polymeric compound, even though it is not absorbed by the skin. [Background technology]

[0002] Products for direct application to the skin are widely known and are formulated in a variety of forms that are compatible with and / or absorbed by the skin, such as emulsions, creams, lotions, serums, gels, powders, oils, sunscreens, etc.

[0003] However, these products can be tedious to apply to the skin, can require extended application or prolonged massage to ensure complete absorption into the dermis, and can leave residue on fingers, hands, or application tools used.

[0004] Some products, especially cosmetics, are applied by means of a physical support, generally fibrous, that facilitates application to the skin, such as makeup remover wipes saturated with special detergent compositions.

[0005] One drawback of this type of product is that after use the fibrous physical support and packaging must be discarded, the former having no other function than support.

[0006] Furthermore, known fibrous physical supports have a specific surface area that does not allow adequate transport and release of the active ingredient.

[0007] The question also arises that, in general, cosmetic compositions for the skin, such as those applied as creams or common pastes, provide for the use of compounds that are functional on the skin and compounds that are functional only in the structure of the formulation.

[0008] Skin-functional compounds are absorbed partially or completely by the skin and provide a benefit to the treated body area. Generally, compounds of this type are so-called active ingredients.

[0009] The compounds functional only in the structure of the formulation contribute to obtaining the composition to be applied, whether it be a milk, serum or liquid, oleolite, water or gel.

[0010] The effect of compounds that are functional only on the structure of the formulation may affect how the composition is stored or the consistency of the composition before and / or during use, and therefore when applied to the skin to be treated.

[0011] For example, compounds that are solely functional in the structure of the formulation can make the composition soft, fluid, or viscous, allow for the formation of a gel, or prevent the separation of oily and aqueous compounds in an emulsion. Furthermore, the solely functional compounds can allow for the preservation of the composition, especially in the presence of water.

[0012] The problem arises that many of the compounds used, being functional in the structure of the formulation, do not bring any benefit to the skin and may actually lead to further deterioration of the treated skin.In fact, some of the compounds that are only functional in the structure of the formulation may remain irrelevant to the skin or may cause, for example, further dryness, blockage of pores, or the development of allergies, dermatitis, etc.

[0013] Among the compounds that are solely functional in the structure of the formulation, it is possible to identify, for example, silicones, petroleum products (e.g. paraffin), alcohols, fragrances, stabilizers, preservatives, emulsifiers, whose main function is to give the formulation of the composition its "silky effect" consistency in contact with the skin and / or to provide stability to the oily part, or to increase the viscosity of a gel formulation and / or to increase the emollient and moisturizing effect of an emulsion.

[0014] For example, a problem that arises with compounds that are only functional in the structure of such formulations is a lack of skin compatibility, which prevents the skin from breathing and leads, for example, to increased dryness, blocked pores and / or even increased sensitization.

[0015] It is also known that the presence of alcohol and preservatives, on the one hand allowing the composition to be preserved, but on the other hand increases the sensitization of the skin, leading to the development of dermatitis, allergies or similar conditions.

[0016] From WO 2021 / 161256 an article is known that comprises a cosmetic patch product based on fibres made of a biocompatible material absorbable by the skin, deposited on a support made of a heat-sealable plastic material, in particular polybutylene succinate adipate (PBSA) or polylactic acid (PLA). [Prior art documents] [Patent documents]

[0017] [Patent Document 1] WO2021 / 161256

[0018] While such patch products address some of the problems discussed above, they still do not fully meet the needs of the industry because the materials used are not fully biodegradable, and are stiff enough that they do not adhere well to uneven areas of the face, especially the nose area.

[0019] Therefore, it is necessary to complete a product that can overcome at least one of the shortcomings of the state-of-the-art technology.

[0020] In particular, one object of the present invention is to provide a product that can be easily and quickly applied to the skin anywhere on the body.

[0021] Another object of the present invention is to provide an article with a biodegradable physical support.

[0022] Another objective is to provide a product with a specific surface area that optimizes the transport and release of active ingredients, if any.

[0023] Applicant has conceived, tested and embodied the present invention to overcome the shortcomings of the state of the art and to obtain these and other objects and advantages. Summary of the Invention

[0024] The invention is set forth and characterized in the independent claims, while the dependent claims describe other features of the invention or variants to the main inventive idea.

[0025] In accordance with the above objectives, in order to solve the technical problems disclosed above in a new and original way, and to achieve significant advantages over the prior art, the article according to the present invention comprises a patch product comprising a membrane substrate absorbable by the skin, formed by at least one electrospun fiber composed of an electrospun first compound and an electrospinning promoter, and a base support on which the patch product is deposited.

[0026] According to one aspect of the present invention, the base support comprises a polysaccharide-based biodegradable film that is not absorbed by the skin. Preferably, the film is made of a polysaccharide, i.e., the polysaccharide is the material that constitutes the film. Advantageously, the polysaccharide is starch.

[0027] In a particularly advantageous embodiment, the base support comprises a polysaccharide-based biodegradable film that is not absorbed by the skin.

[0028] This achieves at least the advantage of having a biodegradable and compostable base support. Polysaccharide supports change rigidity and soften depending on their water absorption, making them inherently conformable and shapeable when applied to the skin. This improves adhesion to uneven areas of the skin, such as the nose, ensuring that the entire surface of the film support adheres to the skin and increasing absorption. Therefore, the base support of the base of the present invention is particularly useful for curved, convex, or concave areas, such as the forehead, temples, cheekbones, cheeks, and eye contours. Another advantage is that the polysaccharide support contains numerous hydroxyl (-OH) groups, making it suitable for moisturizing the skin. This moisturizing effect, combined with the moisturizing effect of the film support, allows the film support to dissolve and penetrate the skin more easily than if the same film support were placed on a support made of a conventional material.

[0029] Furthermore, polysaccharide films, particularly those made from starch, have excellent barrier properties and are therefore suitable for packaging patches.

[0030] According to 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 in this group are not genetically modified.

[0031] Preferably, the starch has a high amylose content, i.e., an amylose concentration of greater than 50% by weight relative to the weight of the starch itself, more preferably greater than 60% by weight, and even more preferably greater than 70% by weight relative to the weight of the starch. Compared to amylopectin, amylose has a more linear and elongated structure, which can facilitate the formation of starch-based films.

[0032] According to another embodiment of the invention, the polysaccharide-based film has a thickness of less than 1 mm, preferably less than 0.5 mm.

[0033] According to another embodiment of the invention, the first compound to be electrospun is a polymer suitable for electrospinning and is selected from the group consisting of a first polysaccharide, collagen, gelatin, albumin, elastin and derivatives thereof. Advantageously, the first polysaccharide is selected from the group consisting of xanthan gum, pectin, chitin, chitosan, dextran, carrageenan, guar gum, agar, cellulose derivatives, starch, gelatin, β-glucan, glycosaminoglycans, mucopolysaccharides, water-soluble polysaccharides and derivatives thereof.

[0034] Preferably, the cellulose derivative is selected from hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC), and sodium carboxymethylcellulose (Na-CMC). The glycosaminoglycan (GAG) or mucopolysaccharide can be selected from chondroitin sulfate, dermatan sulfate, heparin, heparan sulfate, and hyaluronic acid (HA). The water-soluble polysaccharide can be selected from galactomannan, xylan, gum arabic, gum ghatti, glucomannan, acemannan, water-soluble dietary fiber, glycogen, amylose, and polysaccharides derived from plants, bacteria, and fungi.

[0035] According to another embodiment of the present invention, the spinning facilitator is an optionally filler-free vector polymer selected from the group consisting of a second polysaccharide chemically distinct from the first polysaccharide, optionally with the presence of poly(oxyethylene) (PEO). Advantageously, the vector polymer is biocompatible, even optionally without a filler.

[0036] Preferably, the electrospinning enhancer is selected from pullulan and alginate, optionally mixed with poly(oxyethylene). The enhancer can also include a mixture of pullulan and alginate. More preferably, the enhancer is chemically different from the first compound to be electrospun, i.e., the first compound to be electrospun is not pullulan or alginate.

[0037] According to another embodiment of the present invention, the fibers also include a surfactant.

[0038] The surfactants are preferably biosurfactants, i.e. surfactants of biological and organic origin. In particular, surfactants are obtained by fermentation of gram-positive microorganisms. Such surfactants are of biological origin and therefore biocompatible.

[0039] Preferably, the surfactant is selected from lipopeptides, in particular from Bacillus sp. More preferably, the surfactant is selected from the surfactin family, in particular from the group consisting of surfactin, pumilacidin and lichenisin.

[0040] Advantageously, the surfactant is concentrated between 0.1 and 5% by weight, more advantageously between 0.2 and 2% by weight, and even more advantageously between 0.5 and 1% by weight relative to the total weight of the fibers.

[0041] According to some embodiments of the present invention, the electrospun fibers have a flat ribbon shape, i.e., the fibers have an oblong cross section rather than a circular one.

[0042] According to some embodiments, the membrane substrate is in the form of a nonwoven fabric.

[0043] According to another embodiment, the film substrate comprises one or more active ingredients selected from cosmetic active ingredients, pharmaceutical active ingredients and nutritional active ingredients. The expression "active ingredient" means in the present invention and in the present specification a compound that is functional for the body or parts thereof, is partially or completely absorbed by the skin and provides a benefit to the treated body part.

[0044] Advantageously, the one or more active ingredients are selected from one or more peptides and their metabolites or derivatives.The class of peptides that 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 the acetyl tetrapeptides, mention may be made, for example, of acetyl tetrapeptides-9 and acetyl tetrapeptide-11, which are two anti-aging active compounds that act on the skin matrix to improve its structure and affect skin elasticity and firmness, respectively.

[0045] According to some embodiments, the one or more active ingredients include a moisturizing agent, such as, for example, mannitol, a pH adjusting agent, such as, for example, sodium hydroxide, and / or an anti-wrinkle compound, such as, for example, aminobutyric acid.

[0046] One advantage of the articles according to the embodiments described herein is that the patch product contained therein, along with any active ingredients present, such as cosmetic actives, pharmaceutical actives, or nutritional actives, is completely absorbed into the skin. In addition to being complete, absorption is also rapid, with total absorption of the patch product of the articles according to the present invention being observed to occur within minutes of application to the skin.

[0047] Another advantage is that the form in which the product is provided does not involve a formulation that requires the presence of functional compounds only in its structure, since the active ingredient is retained and delivered by the membrane substrate, which is completely biocompatible and absorbed into the skin, without any risk or damage to the skin itself.

[0048] Another advantage of using cosmetic, pharmaceutical, or nutritional products is the possibility of achieving much higher local concentrations of the target compound than can be achieved with conventional formulations. Even with polysaccharides, collagen, gelatin, albumin, elastin, and their low molecular weight derivatives, achieving high concentrations is virtually impossible because the viscosity of the product becomes too high and cannot exceed 5-10% by weight. This article allows cosmetic, pharmaceutical, or nutritional products to be applied to the skin with concentrations of the target compound up to 50% by weight.

[0049] According to another aspect of the present invention, a method for manufacturing an article comprising a patch product disposed on a base support comprises the step of electrospinning a composition comprising a first compound to be electrospun and an electrospinning enhancer to obtain electrospun fibers, wherein the electrospun fibers are deposited directly on a base support made of a polysaccharide-based biodegradable film, preferably starch, that is not absorbed by the skin.

[0050] In a particularly advantageous embodiment, the base support consists of a polysaccharide-based biodegradable film that is not absorbed by the skin.

[0051] According to 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 in this group are not genetically modified.

[0052] Preferably, the starch has a high amylose content, i.e., an amylose concentration of greater than 50% by weight relative to the weight of the starch itself, more preferably greater than 60% by weight, and even more preferably greater than 70% by weight relative to the weight of the starch. Compared to amylopectin, amylose has a more linear and elongated structure, which can facilitate the formation of starch-based films.

[0053] According to another embodiment of the invention, the polysaccharide-based film has a thickness of less than 1 mm, preferably less than 0.5 mm.

[0054] Advantageously, the biocompatible polymeric material to be electrospun and / or the electrospinning facilitating agent are as described above.

[0055] According to some embodiments, the composition also comprises a surfactant.

[0056] The surfactants are preferably biosurfactants, i.e. surfactants of biological and organic origin. In particular, surfactants are obtained by fermentation of gram-positive microorganisms. Such surfactants are of biological origin and therefore biocompatible.

[0057] Preferably, the surfactant is selected from lipopeptides, in particular from Bacillus sp. More preferably, the surfactant is selected from the surfactin family, in particular from the group consisting of surfactin, pumilacidin and lichenisin.

[0058] Advantageously, the surfactant is concentrated between 0.1 and 5% by weight, more advantageously between 0.2 and 2% by weight, and even more advantageously between 0.5 and 1% by weight relative to the total weight of the fibers.

[0059] According to another embodiment, the composition comprises one or more active ingredients selected from cosmetic active ingredients, pharmaceutical active ingredients and nutritional active ingredients.

[0060] Advantageously, the one or more active ingredients are selected from one or more peptides and their metabolites or derivatives.The class of peptides that 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 the acetyl tetrapeptides, mention may be made, for example, of acetyl tetrapeptides-9 and acetyl tetrapeptide-11, which are two anti-aging active compounds that act on the skin matrix to improve its structure and affect skin elasticity and firmness, respectively.

[0061] According to some embodiments, the one or more active ingredients include a moisturizing agent, such as, for example, mannitol, a pH adjusting agent, such as, for example, sodium hydroxide, and / or an anti-wrinkle compound, such as, for example, aminobutyric acid.

[0062] According to another aspect of the invention, the primary packaging comprises a sealed pouch in which the article as described above is enclosed. According to some embodiments, the pouch comprises two sheets of heat-sealable material welded together. Advantageously, the two sheets are welded together around their peripheries to form an interior space suitable for enclosing the article.

[0063] According to another aspect of the present invention, the secondary packaging includes a box and a plurality of the above-described primary packages enclosed within the box. [Brief explanation of the drawings]

[0064] These and other aspects, features and advantages of the present invention will become apparent from the following description of one embodiment, given as a non-limiting example with reference to the accompanying drawings, in which: [Figure 1] FIG. 1 is a graph showing the change in skin moisturization when an article of the present invention including a patch product and a placebo product are applied. [Figure 2] FIG. 2 is a graph showing the change in skin elasticity when an article of the present invention including a patch product and a placebo product are applied. [Figure 3]FIG. 3 is a graph showing the change in collagen density in the skin when an article of the present invention including a patch product and a placebo product are applied. [Figure 4] FIG. 4 is a graphical representation of the change in collagen presence in skin treated with an article of the present invention, including a patch product, compared to untreated skin. [Figure 5] FIG. 5 is a graphical representation of the change in collagen presence in skin treated with an article of the present invention, including a patch product, compared to untreated skin.

[0065] It is to be made clear that the expressions and terms used in this specification, as well as the figures depicted in the accompanying drawings, all have the sole function of making the description of this specification easier to understand and of better explaining the invention, which is to provide a non-limiting example of the invention itself, the scope of protection of which is defined by the claims.

[0066] To facilitate understanding, the same reference numbers have been used wherever possible to identify identical common elements in the figures, and it will be understood that elements and features of one embodiment may be conveniently combined with or incorporated into other embodiments without the need for further description. DETAILED DESCRIPTION OF THE INVENTION

[0067] Unless otherwise defined, all technical and scientific terms used herein and hereinafter have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, such methods and materials are described below by way of example. In case of conflict, the present application, including definitions, will control. The materials, methods, and examples are intended to be illustrative only and are not to be construed as limiting.

[0068] All measurements were made at 25°C (room temperature) and atmospheric pressure unless otherwise noted. All temperatures are in degrees Celsius unless otherwise noted.

[0069] All percentages and ratios given are intended to indicate weight by weight (w / w) of the total composition unless otherwise specified.

[0070] Percentage ranges shown herein are assumed to total 100% for all components unless otherwise specified.

[0071] All ranges set forth herein are intended to include the extreme values ​​as well as convey a range "between" two values ​​unless otherwise specified.

[0072] The present disclosure also includes ranges that can be derived by overlapping or combining two or more disclosed ranges, unless otherwise indicated.

[0073] The present disclosure also includes ranges that may be derived from the combination of two or more values ​​measured at different points, unless otherwise specified.

[0074] Where water is listed, it is distilled water unless otherwise specified.

[0075] An article according to the present invention includes a patch product disposed on a base support.

[0076] The patch product is applied to the skin and consists of an electrospun membrane substrate in the form of a nonwoven fabric, containing at least one electrospun fiber, particularly at least one nanofiber. This form is obtained by gradually depositing the fiber onto a base support during electrospinning. The fiber is gradually deposited in multiple overlapping layers. Multiple fibers can be provided, and multiple fibers can be simultaneously applied to the same support, for example.

[0077] The base support is comprised of a biodegradable film made from starch, particularly non-genetically modified corn starch. Alternatively, starch from other sources, such as potato, wheat, tapioca, or rice, can be used, particularly as long as it is not genetically modified. The base support can also have other layers of other materials associated with the biodegradable starch film.

[0078] The starch used may be of the high amylose content type. High amylose starch means a starch having an amylose content of 50% or more by weight, particularly 60% or more by weight, or 75% or more by weight, based on the weight of the starch. For example, the starch may contain about 80% by weight of amylose and 17% by weight of amylopectin. "Normal" starch contains about 17% by weight of amylose and about 80% by weight of amylopectin.

[0079] Higher concentrations of amylose, which is substantially linear (unbranched) and has a longer molecular structure than amylopectin, favor the formation of stronger, more stable films.

[0080] Typically, the starch film used for the base support has a thickness between 45 μm and 110 μm, especially between 50 μm and 100 μm, is light in color, and can be provided in the form of a reel with a width of about 1 m. The film has a density of 1.35 to 1.45 g / cm. 3 (measured according to ASTM D792 standard), a Vicat softening temperature of 130°C to 135°C (measured according to ASTM D1525 standard), a glass transition temperature of 130°C to 135°C (measured by the DMA method at 50% humidity), and / or a water activity of 0.50 to 0.65 (measured according to the PTM 03 method). Such a water activity value indicates that the starch film has a tendency to absorb water, which at least partially softens it and favors its deformation to better adhere to the skin in uneven areas.

[0081] Advantageously, the film has a modulus of elasticity between 2000 MPa and 3500 MPa, preferably between 2800 MPa and 3000 MPa, a tensile strength between 25 MPa and 60 MPa, preferably between 35 MPa and 50 MPa, and a stress at break of more than 20%, these values ​​being measured in the machine direction (MD) according to the ASTM D882 standard.

[0082] The static friction coefficient of the film is 0.15 to 0.25, preferably 0.21, and the dynamic friction coefficient is 0.10 to 0.25, preferably 0.17. These friction coefficients are measured according to the ASTM D1894 standard.

[0083] The film also has a water vapor transmission rate of 100-180g / m2 at 38°C and 75% humidity. 2 / 24 hours, preferably 140g / m 2 / 24 hours (measured according to ASTM E9600 standard) and oxygen permeability of 1-2 (cc. 25 μm / m 2 / atm / day), preferably under 50% humidity conditions, 1.60 (cc. 25 μm / m 2 / atm / day) (measured according to ASTM D1434 standard).

[0084] Advantageously, the base support is transparent, allowing visualization of the dissolution and absorption of the film substrate on the skin during application. Obviously, this assumes that the film substrate is not transparent. Advantageously, the film has a transparency (measured according to the ASTM D1003 standard) of 3 to 20%, preferably 6 to 10%, a 60° specular gloss (measured according to the ASTM D2457 standard) of 70% to 90%, preferably 80% to 85%, and a light transmittance (measured according to the ASTM D1003 standard) of greater than 85%, preferably greater than 90%, more preferably 95% to 98%.

[0085] Electrospinning is achieved by feeding a special composition through an electrospinning head under an electric field. The fibers emerging from the electrospinning head are deposited onto a base support made of a starch film. Relative motion between the electrospinning head and the base support results in the formation of a nonwoven fabric.

[0086] Preferably, the fibers are continuous, homogeneous in composition, and have a substantially smooth surface. The fibers are also preferably defect-free, i.e., free of substrate buildup or droplets that may form during electrospinning.

[0087] Electrospun fibers can have a flat ribbon-like or oval cross section.

[0088] Advantageously, the cross section of the electrospun fiber has a maximum transverse size on the order of nanometers and micrometers, and is less than 100 μm, more preferably less than 50 μm, even more preferably less than 25 μm, and most preferably on the order of 10 μm. The transverse size of the substrate fiber can start from 10 nanometers, for example, 50 nm. It should be noted that the transverse size does not vary substantially along the entire fiber. By substantially not varying transverse size, it is meant that the diameter can vary by no more than 30% of the average measurement.

[0089] Fibers with this shape and these sizes have a larger surface / volume ratio than known fibers, generally with diameters above 100 μm, and also have higher mechanical and structural properties, resulting in higher efficiency and performance compared to the industry standard. The large specific surface area of ​​the resulting fibers is particularly suitable for the transport and release of active ingredients. The resulting nanofibers have a diameter of 1-30 m. 2 / g, preferably 2 to 20m 2 / g specific surface area.

[0090] These fibers make it possible to obtain membrane substrates that are generally white, or in any case light in color.

[0091] The membrane substrate is composed of an electrospinnable biocompatible polymeric material selected from the group consisting of xanthan gum, pectin, chitin, chitosan, dextran, carrageenan, guar gum, agar, hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC), sodium carboxymethylcellulose (Na-CMC), albumin, starch, gelatin, collagen, elastin, β-glucan, chondroitin sulfate, dermatan sulfate, heparin, heparan sulfate, hyaluronic acid (HA), galactomannan, xylan, gum arabic, gum ghatti, glucomannan, acemannan, water-soluble dietary fiber, glycogen, amylose, polysaccharides derived from plants, bacteria, and fungi, and derivatives thereof.

[0092] These compounds or classes of compounds have the property of being able to modify the viscosity of liquids and are suitable for forming regular electrospun fibers with good mechanical and absorption properties, all of which are biocompatible, naturally occurring, and can be used in the food, pharmaceutical, and / or cosmetic sectors.

[0093] In particular, xanthan gum, dextran, carrageenan, Na-CMC, starch, gelatin, and ghatti gum are used in the food industry as thickeners, stabilizers, and sometimes gelling agents. Furthermore, xanthan gum is used in the pharmaceutical and cosmetic industries as a stabilizer for suspensions and emulsions, guar gum as a thickener and gelling agent, and carrageenan as an inert excipient in pharmaceuticals. Dextran is also used as a thickener in pharmaceuticals.

[0094] Chitosan is used in the food sector in low-calorie diets and in the pharmaceutical sector as an excipient, especially in inhaled products, while pectin is used in the food sector as a gelling agent and in the pharmaceutical sector as a nutritional supplement and probiotic agent.

[0095] Agar, galactomannan and glucomannan are used as gelling agents in the nutritional field.

[0096] Among cellulose derivatives, HPMC is used as a stabilizer and viscosity modifier in the food industry and as an excipient for eye drops and oral medications in the pharmaceutical industry. HPC is used as a food additive and as a binder for eye drops and tablets in the pharmaceutical industry. HEC is used as a thickener and gelling agent in the pharmaceutical and cosmetic industries.

[0097] Beta-glucans, like xylans, are commonly used as dietary fiber. Chondroitin sulfate is used as a nutritional supplement and as a treatment for osteoarthritis. Dermatan sulfate, heparin, and heparan sulfate are known in the pharmaceutical field as anticoagulants.

[0098] Gum arabic is used in the food industry as a stabilizing excipient and viscosity modifier, while acemannan is known in the pharmaceutical industry for its immunostimulatory properties.

[0099] It should be noted that some of these compounds have unique functions in the cosmetic, pharmaceutical or food fields, such as starch, elastin, hyaluronic acid, heparin, collagen, pectin, β-glucan, chondroitin sulfate, dermatan sulfate, heparan sulfate and their derivatives, etc. Therefore, it is advantageous to electrospin these compounds, since by applying the corresponding fibers, these compounds can be applied in larger amounts than in known solutions, resulting in a greater effect.

[0100] When the biocompatible polymeric material to be electrospun is hyaluronic acid, it can be linear or cross-linked, and can have a high mass, for example, 1 million daltons or more, or a low mass, typically 10,000 daltons or less. It is also possible to provide a mixture of linear and cross-linked hyaluronic acid, thereby adjusting the stiffness of the resulting yarn and the three-dimensional structure of the film obtained by depositing the yarn on a support.

[0101] The membrane substrate composition also includes at least one electrospinning facilitator, which is a highly biocompatible, uncharged vector polymer selected from alginate, optionally in the presence of PEO, and pullulan. The spinning facilitator is preferably pullulan, as this provides the best results.

[0102] When alginate is mixed with PEO, they can be diluted separately in water or a water-based solution at concentrations of 0.1% to 30% by weight, preferably 1% to 20% by weight, and more preferably 5% to 15% by weight. The alginate:PEO mixture, if present, is preferably prepared in a weight ratio of 5:1 to 1:5, more preferably 2:1 to 1:2. The best electrospinning results have been achieved with a weight ratio equal to 1:1.

[0103] Pullulan can be diluted in water or a water-based solution at a concentration of 0.1% to 30% by weight, preferably 1% to 20% by weight, more preferably 5% to 15% by weight.

[0104] The polymeric material to be electrospun and the accelerator are preferably mixed in a weight ratio of (first compound): accelerator of 10:1 to 1:10, more preferably 5:1 to 1:5, and even more preferably 2:1 to 1:2. It has been found that best results can be achieved with compositions in which the weight ratio of first compound to accelerator is equal to 1:1.

[0105] The membrane substrate also includes a biosurfactant, ie, a surfactant selected from surfactants of biological and organic origin, as opposed to surfactants of bacterial origin.

[0106] In particular, the surfactant of the composition is advantageously obtained by fermentation of a gram-positive microorganism.

[0107] More precisely, the biosurfactant is chosen from lipopeptides, in particular those derived from the fermentation of organisms of the genus Bacillus, more particularly those with a low molecular weight, for example those with a molecular weight of at most 10,000 g / mol, preferably at most 5,000 g / mol, more preferably at most 2,500 g / mol.

[0108] Among these lipopeptides, there are several families, including surfactins, iturins, fengicins, crustatins, and rocillomycins. These lipopeptide families 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. However, all of them have surfactant properties.

[0109] Preferably, the biosurfactant of the composition is selected from the family of surfactins.

[0110] The surfactin family includes surfactin itself, which is produced by various branches of the Bacillus genus, particularly B. subtilis, but also by other branches such as B. natto and B. circulans. Its structure contains a lactone ring formed by a characteristic chiral sequence of seven amino acids (L-Glu, L-Leu, D-Leu, L-Val, L-Asp, D-Leu, L-Leu, with the first and last amino acids joined by an ester bond to form the lactone ring). Surfactins contain a β-hydroxy fatty acid chain with 13 to 16 carbon atoms. More than 30 congeners of surfactin are known, all of which share the same chiral sequence of amino acids in the lactone ring, LLDLLDL. Congeners refer to molecules of the same genus but are not isomers.

[0111] The surfactin family also includes pumilacidins, which are derived from the variant AF of the B. pumilus branch. Compared to surfactins, the amino acid at position 7 is substituted with L-Val or L-Ile.

[0112] Finally, the surfactin family includes lichenisins, which are obtained primarily from B. licheniformis, and which differ from surfactins in that position 1 of the lactone ring of L-glutamic acid is replaced by L-glutamine.

[0113] Surfactins, pumilacidins, and lichenicins contain five hydrophobic residues (Leu, Val, or Ile) and long secondary aliphatic chains, giving them strong surface-active properties. In fact, highly purified surfactin family compounds have been shown to reduce the surface tension of water from 72 mN / m to 27 mN / m at a concentration of 0.0005 wt%. Surfactins are particularly suitable for electrospinning in aqueous solutions because they are stable and soluble in water over a wide pH range (5–13) and temperature.

[0114] Preferably, the biosurfactant is a surfactin or a biosurfactin.

[0115] Generally, the biosurfactant will be present at a concentration of less than 5% by weight, preferably less than 2% by weight, more preferably between 0.5% and 1% by weight of the composition.

[0116] Preferably, the composition also comprises at least one active ingredient of pharmaceutical, nutritional and / or cosmetic type.

[0117] It should be noted that an active ingredient can have different types of functions, regardless of its field of action.

[0118] Cosmetic active ingredients can be of the following types: antiseborrheic agents (e.g., sebacic acid, azelaic acid), antisebum agents (e.g., coal dust), antibacterial agents (e.g., climbazole, piroctone olamine), antioxidants (e.g., ascorbic acid, tocopherol, coenzyme Q10, resveratrol, glutathione), antiperspirants (e.g., aluminum chlorohydrate, aluminum sesquichlorohydrate), astringents (e.g., Mexican lime flower extract, calcium lactate), bleaching agents (e.g., glabridin, ammonium persulfate), makeup removers (e.g., sodium cocoyl glutamate), deodorants (e.g., triethyl citrate, zinc ricinoleate), exfoliants (e.g., glycerin ... Cholic acid, malic acid, mandelic acid), fragrances (e.g., citral, honey), perfumes (e.g., d,l-limonene, coumarin), humectants (e.g., glycerin, propanediol), keratolytic agents (e.g., chloroacetic acid, salicylic acid), moisturizers (e.g., aloe arborescens leaf extract), fragrances (e.g., geraniol, linalool), emollients (e.g., triolein, squalene), cooling agents (e.g., menthol, menthyl lactate), skin moisturizers (e.g., panthenol, allantoin), skin protectants (e.g., sphingolipids, zinc oxide), smoothing agents (e.g., castor bean seed oil), soothing agents (e.g., Hamamelis virginiana), virginiana extract, Chamomile Retrotic extract, Bisabolol) or tonics (e.g., Arnica montana, Capsicum frutescens extract), UV filters (e.g., Methylenebisbenzotriazolyltetramethylbutylphenol, Ethylhexyl methoxycinnamate, Caffeine, Theine, Theobromine, Theophylline), anti-wrinkle agents (e.g., aminobutyric acid, etc.), one or more peptides and their metabolites and derivatives (e.g., essential amino acids and branched amino acids, tetrapeptides).

[0119] The active pharmaceutical ingredient may be the following: 5-α-reductase inhibitors (e.g., finasteride), 5-aminosalicylates (e.g., mesalamine), 5-HT3 receptor antagonists (e.g., ondansetron), ACE inhibitors with calcium channel blockers (e.g., amlodipine / benazepril), thiazide ACE inhibitors (e.g., hydrochlorothiazide), adamantane antiviral drugs (e.g., amantadine), adrenocortical hormone inhibitors (e.g., aminoglutethimide), adrenergic bronchodilators (e.g., albuterol), and drugs for treating hypertensive emergencies (e.g., diazoxide). ), drugs for treating pulmonary hypertension (e.g., treprostinil), aldosterone receptor antagonists (e.g., spironolactone), alkylating agents (e.g., cyclophosphamide), allergens (e.g., house dust mite allergen extract), α-glucosidase inhibitors (e.g., miglitol), amebicides (e.g., metronidazole), aminoglycosides (e.g., tobramycin), aminopenicillins (e.g., amoxicillin), aminosalicylates (e.g., aminosalicylic acid), AMPA receptor antagonists (e.g., perampanel), amylase inhibitors (e.g., ceftazidime), ceftazidime, ... androgens and anabolic steroids (e.g., testosterone), angiotensin-converting enzyme inhibitors (e.g., ramipril), angiotensin II inhibitors with calcium channel blockers (e.g., amlodipine / olmesartan), thiazide angiotensin II inhibitors (e.g., hydrochlorothiazide / olmesartan), angiotensin receptor blockers (e.g., valsartan), angiotensin receptor blockers and neprilysin inhibitors. Anti-inflammatory drugs (e.g., sacubitril / valsartan), anorectal medications (e.g., hydrocortisone / pramoxine), appetite suppressants (e.g., phentermine), antacids (e.g., magnesium hydroxide), anthelmintics (e.g., pyrantel), anti-angiogenic eye drops (e.g., aflibercept), anti-CTLA-4 monoclonal antibodies (e.g., ipilimumab), anti-PD-1 monoclonal antibodies (e.g., nivolumab), thiazide (central) antiadrenergics (e.g., hydrochlorothiazide / methyldopa), thiazide (peripheral) antiadrenergics (e.g.,polythiazide / prazosin), centrally acting antiadrenergics (e.g., guanfacine), peripherally acting antiadrenergics (e.g., tamsulosin), antiandrogens (e.g., enzalutamide), antianginals (e.g., nitroglycerin, dyphylline / guaifenesin), antibiotics (e.g., metronidazole), antibiotics / antineoplastics (e.g., doxorubicin), anticholinergic antiemetics (e.g., diphenhydramine), anticholinergic antiparkinsonian drugs (e.g., procyclidine), anticholinergic bronchodilators (e.g., tiotropicin), e.g., Anticholinergics / anticonvulsants (e.g., hyoscyamine), anticoagulants (e.g., phytonadione), antiepileptics (e.g., lacosamide), antidepressants (e.g., bupropion), antidiarrheals (e.g., loperamide), antidiuretic hormones (e.g., desmopressin), antidotes (e.g., naltrexone, dronabinol), antifungals (e.g., griseofulvin), antigonadotropins (e.g., danazol), antigout drugs (e.g., colchicine), antihistamines (e.g., cetirizine), hypolipidemic drugs and their combinations (e.g., ezetimibe / simvastatin), Antihyperuricemia drugs (e.g., febuxostat), antimalarials (e.g., doxycycline), antimalarial combination drugs, antimalarial quinolines (e.g., hydroxychloroquine), antimanic drugs (e.g., lithium), antimetabolites (e.g., capecitabine), antimigraine drugs (e.g., rizatriptan), antineoplastic drugs (e.g., isotretinoin), antineoplastic combination drugs (e.g., letrozole / ribociclib), antineoplastic antidotes (e.g., amifostine), antineoplastic interferon drugs (e.g., interferon α-2b), antipseudomonal penicillin drugs (e.g., carbenicillin), antipsoriatic drugs (e.g., acitretin), antipsychotic drugs (e.g., haloperidol), antirheumatic drugs (e.g., adalimumab), antiseptics and disinfectants, antithyroid drugs (e.g., potassium iodide), antitoxins and antivirals (e.g., polyvalent antivenom serum (pit viper)), antitussives (e.g., dextromethorphan), antiviral boosters (e.g., ritonavir), antiviral interferons (e.g., pegylated interferon α-2a), aromatase inhibitors (e.g., anastrozole), atypical antipsychotics (e.g., aripiprazole),Azole antifungals (e.g., fluconazole), bacterial vaccines (e.g., 13-valent pneumococcal vaccine), barbiturates (e.g., primidone), barbiturates (e.g., phenobarbital), BCR tyrosine kinase inhibitors (ABL) (e.g., imatinib), benzodiazepines (e.g., diazepam), benzodiazepines (e.g., clonazepam), thiazide beta-blockers (e.g., bisoprolol / hydrochlorothiazide), beta-lactamase inhibitors (e.g., clavulanic acid), bile acid absorption inhibitors (e.g., cocaine, rusevelam), bisphosphonates (e.g., zoledronic acid), BTK inhibitors (e.g., ibrutinib), calcium receptor agonists (e.g., cinacalcet), calcineurin inhibitors (e.g., tacrolimus), calcitonin, calcium channel blockers (e.g., verapamil), carbamate anticonvulsants (e.g., felbamate), carbapenems (e.g., doripenem), carbapenem / β-lactamase inhibitors (e.g., meropenem / vaborbactam), carbonic anhydrase inhibitors (e.g., topiramate), carbonic anhydrase inhibitors (e.g., acetazolamide ), stress factors regenosidase, cardioselective beta-blockers (e.g., nebivolol), catecholamines (e.g., epinephrine), anti-CD20 monoclonal antibodies (e.g., ocrelizumab), anti-CD30 monoclonal antibodies (e.g., brentuximab), anti-CD33 monoclonal antibodies (e.g., gemtuzumab), anti-CD38 monoclonal antibodies (e.g., anti-CD52 monoclonal antibody alemtuzumab), CDK4 / 6 inhibitors (e.g., palbociclib), cephalosporins / beta-lactamase inhibitors (e.g., avibactam / ceftazidime), Ceruminoleptics (e.g., urea peroxide), CFTR combination drugs (e.g., ivacaftor / lumacaftor), CFTR potentiators (e.g., ivacaftor), CGRP inhibitors (e.g., erenumab), chelating agents (e.g., deferasirox), chemokine receptor antagonists (e.g., maraviroc), chloride channel activators (e.g., lubiprostone), cholesterol absorption inhibitors (e.g., ezetimibe), cholinergic agonists (e.g., cevimeline), cholinergic muscle stimulants (e.g., pyridostigmine), cholinesterase inhibitors (e.g., donepezil),Central nervous system stimulants (e.g., phentermine), colony-stimulating factors (e.g., filgrastim), contraceptives (e.g., levonorgestrel), corticotropin, coumarins and indanediones (e.g., warfarin), COX-2 inhibitors (e.g., celecoxib), decongestants (e.g., pseudoephedrine), diarylquinolines, benzodiazepine anticonvulsants (e.g., carbamazepine), digestive enzymes (e.g., lactase), dipeptidyl peptidase 4 inhibitors (e.g., sitagliptin), dopaminergic antiparkinsonian drugs (e.g., , ropinirole), drugs used for alcohol dependence (e.g., acamprosate), echinocadins (e.g., caspofungin), inhibitors (e.g., erlotinib), estrogen receptor antagonists (e.g., fulvestrant), estrogens (e.g., estradiol), expectorants (e.g., guaifenesin), factor XA inhibitors (e.g., rivaroxaban), drug-derived anticonvulsants (e.g., divalproex sodium), fibric acid derivatives (e.g., fenofibrate), first-generation cephalosporins (e.g., cephalexin, cephalosporins (e.g., cefepime), gallstone dissolving agents (e.g., ursodiol), gamma-aminobutyric acid analogues (e.g., gabapentin), gamma-aminobutyric acid reuptake inhibitors (e.g., tiagabine), general anesthetics (e.g., propofol), GI stimulants (e.g., metoclopramide), glucocorticoids (e.g., budesonide), glucose-elevating agents (e.g., glucagon), glycoprotein antibiotics (e.g., vancomycin), platelet glycoprotein inhibitors (e.g., tirofiban), glycylcyclines (e.g., tigecycline) , gonadotropin-releasing hormones (e.g., leuprolide), gonadotropin-releasing hormone antagonists (e.g., elagolix), gonadotropins (e.g., chorionic gonadotropin), Group I antiarrhythmics (e.g., phenytoin), Group II antiarrhythmics (e.g., propranolol), Group III antiarrhythmics (e.g., dronedarone), Group IV antiarrhythmics (e.g., verapamil), Group V antiarrhythmics (e.g., digoxin), growth hormone receptor antagonists (e.g., pegvisomant), growth hormones (e.g., somatropin),Guanylate cyclase-C agonists (e.g., linaclotide), Helicobacter pylori eradication drugs (e.g., bismuth subcitrate potassium / metronidazole / tetracycline), H2 antagonists (e.g., ranitidine), hedgehog pathway inhibitors (e.g., vismodegib), heparin antagonists (e.g., protamine), HER2 inhibitors (e.g., neratinib), herbal products (e.g., neratinib), 5-hydroxytryptophan, aloe vera), histone deacetylase inhibitors (e.g., romidepsin), hormones / antineoplastic agents (e.g., medroxyprogesterone) , hydantoin anticonvulsants (e.g., phenytoin), hydrazide derivatives (e.g., isoniazid), immunoglobulins, impotence drugs (e.g., sildenafil), incretin mimetics (e.g., liraglutide), cardiac inotropes (e.g., digoxin), insulin and its derivatives (e.g., insulin glargine), insulin-like growth factors (e.g., mecasermin), interferons (e.g., interferon beta-1A), interleukin inhibitors (e.g., dupilumab), interleukins (e.g., aldesleukin), iron preparations (e.g., I sulfate iron), ketolides (e.g., telithromycin), laxatives (e.g., bisacodyl), antileprosy drugs (e.g., clofazimine), leukotriene modifiers (e.g., montelukast), lincomycin derivatives (e.g., clindamycin), loop diuretics (e.g., furosemide), lysosomal enzymes (e.g., imiglucerase), macrolides (e.g., azithromycin), mast cell stabilizers (e.g., cromolyn), meglitinides (e.g., repaglinide), melanocortin receptor agonists (e.g., bremelanotide), methylxanthines (e.g., teocorticoids), steroids), mineralocorticoids (e.g., fludrocortisone), minerals and electrolytes (e.g., citric acid / potassium citrate), various antiviral drugs (e.g., baloxavir marboxil), various anxiolytics, sedatives, hypnotics (e.g., zolpidem), various bone resorption inhibitors (e.g., denosumab), various cardiovascular drugs (e.g., midodrine), various central nervous system drugs (e.g., dalfampridine), various coagulation regulators (e.g., tranexamic acid), various diuretics (e.g., pamabrom), various urogenital system drugs (e.g., phenazopyridine), various gastrointestinal system drugs (e.g.,misoprostol), various metabolic drugs (e.g., burosumab), various respiratory system drugs (e.g., α1-proteinase inhibitors), various topical medications (e.g., sodium hyaluronate), various vaginal medications (e.g., estradiol), mitotic inhibitors (e.g., vincristine), monoamine oxidase inhibitors (e.g., phenelzine), pharyngeal and oral products (e.g., fluoride), mTOR inhibitors (e.g., everolimus), mucolytics (e.g., acetylcysteine), mutansase inhibitors (e.g., sorafenib), narcotic analgesic combinations (e.g., buprenorphine / nalox), buprenorphine / naloxone), narcotic analgesics (e.g., fentanyl), natural penicillins (e.g., penicillin v potassium), neuraminidase inhibitors (e.g., oseltamivir), neuronal potassium channel openers (e.g., ezogabine), new generation cephalosporins (e.g., ceftaroline), NHE3 inhibitors (e.g., ceftaroline), nicotinic acid derivatives (e.g., ethionamide), NK1 receptor antagonists (e.g., aprepitant), NNRTIs (e.g., efavirenz), non-cardioselective beta-blockers (e.g., carvedilol), non-sulfonylureas (e.g., metformin), non-steroidal anti-inflammatory drugs (e.g., diclofenac), NS5A inhibitors (e.g., daclatasvir), nucleoside reverse transcriptase inhibitors (NRTIs) (e.g., tenofovir), dietary supplements (e.g., omega-3 polyunsaturated fatty acids), oral nutritional supplements (e.g., omega-3 polyunsaturated fatty acids), arginine), other immunostimulants (e.g., glatiramer), other immunosuppressants (e.g., omalizumab), oxazolidinedione anticonvulsants (e.g., trimethadione), oxazolidinedione antibiotics (e.g., linezolid), PTH and analogs (e.g., teriparatide), PARP inhibitors (e.g., niraparib), PCSK9 inhibitors (e.g., evolocumab), penicillinase-resistant penicillins (e.g., oxacillin), peripheral opioid receptor agonists (e.g., naloxegol), mixed peripheral opioid receptor antagonists (e.g., , agonist / antagonist eluxadoline), peripheral vasodilators (e.g., isoxsuprine), peripherally acting antiobesity drugs (e.g., orlistat), phenothiazine antiemetics (e.g., promethazine), phenothiazine antiemetics (e.g., promethazine), phenothiazine antipsychotics (e.g., prochlorperazine), phenylpiperazine antidepressants (e.g., trazodone), potassium phosphate inhibitors (e.g., trazoderone), (e.g., idelalisib), platelet aggregation inhibitors (e.g., aspirin), platelet stimulants (e.g., eltrombopag), polyenes (e.g.,nystatin), potassium-sparing diuretics (e.g., spironolactone), probiotics (e.g., Lactobacillus acidophilus), modulator receptor inhibitors (e.g., ulipristal), progestins (levonorgestrel), prolactin inhibitors (e.g., cabergoline), protease inhibitors (e.g., telaprevir), protease-activated receptor-1 antagonists (e.g., vorapaxar), proteasome inhibitors (e.g., bortezomib), proton pump inhibitors (e.g., omeprazole), psoralens (e.g., methoxsalen), purine nucleosides (e.g., valacyclovir), pyrrolidine anticonvulsants (e.g., levetiracetam), quinolones (e.g., ciprofloxacin), genetic recombinants Human erythropoietin (e.g., epoetin alfa), renin inhibitors (e.g., aliskiren), rifamycin derivatives (e.g., rifampicin, salicylates (e.g., aspirin), second-generation cephalosporins (e.g., cefuroxime), selective receptor modulators (e.g., ospemifene), selective immunosuppressants (e.g., natalizumab), selective phosphodiesterase-4 inhibitors (e.g., roflumilast), selective serotonin reuptake inhibitors (e.g., escitalopram), serotonin ... receptor modulators (e.g., escitalopram), serotonin receptor agonists (e.g., escitalopram), serotonin receptor agonists (e.g., escitalopram), serotonin receptor agonists (e.g., escitalopram), serotonin receptor agonists (e.g., escital norepinephrine reuptake inhibitors (e.g., duloxetine), serotonergic enteric neuromodulators (e.g., tegaserod), SGLT-2 inhibitors (e.g., empagliflozin), skeletal muscle relaxants (e.g., onabotulinumtoxinA), smoking cessation aids (e.g., nicotine analogs somatostatin) (e.g., octreotide), statins (e.g., lovastatin), streptogramins (e.g., dalfopristin / quinupristin), streptomycin derivatives (e.g., capreomycin), Anticonvulsants succinamides (e.g., ethosuximide), sulfonamides (e.g., sulfamethoxazole), sulfonylurea stimulants (e.g., glimepistol, clomiphene), tetracyclic antidepressants (e.g., mirtazapine), tetracycline antibiotics (e.g., minocycline), thiazide diuretics (e.g., hydrochlorothiazide), thiazolidinediones (e.g., pioglitazone), thioxanthenes (e.g., thiothixene), third-generation cephalosporins (e.g., ceftriaxone),Thrombin inhibitors (e.g., dabigatran), streptolytics (e.g., levothyroxine), TNFα inhibitors (e.g., adalimumab), tocolytics (e.g., terbutaline), topical acne medications (e.g., tretinoin), local anesthetics (e.g., lidocaine), topical anti-infectives (e.g., malathion), topical rosacea medications (e.g., ivermectin), topical antibiotics (e.g., silver sulfadiazine), topical antifungals (e.g., econazole), topical antihistamines (e.g., diazepam ... phenhydramine), topical antineoplastic agents (e.g., imiquimod), topical antipsoriatic agents (e.g., tazarotene), topical antiviral agents (e.g., penciclovir), topical astringents (e.g., hazelnut), topical debridement agents (e.g., collagenase), topical bleaching agents (e.g., hydroquinone), topical emollients (e.g., emollients), topical keratolytic agents (e.g., salicylic acid), topical nonsteroidal anti-inflammatory agents (e.g., diclofenac), topical photochemical agents (e.g., aminole topical steroids (e.g., betamethasone), topical steroids including anti-infectives (e.g., acyclovir / hydrocortisone), transthyretin stabilizers (e.g., tafamidis), triazine anticonvulsants (e.g., lamotrigine), tricyclic antidepressants (e.g., amitriptyline), urea cycle disorder agents (e.g., sodium phenylbutyrate), urinary tract anti-infectives (e.g., nitrofurantoin), urinary tract antispasmodics ... mitriptyline), regulators (e.g., potassium citrate), uterotonics (e.g., dinoprostone), bacterial vaginosis medications (e.g., clindamycin), vasodilators (e.g., alprostadil), vasopressin antagonists (e.g., conivaptan), vasoconstrictors (e.g., epinephrine), VEGF / VEGFR inhibitors (e.g., pazopanib), viral vaccines, vitamin / mineral combinations, vitamins (e.g., cyanocobalamin), VMAT2 inhibitors (e.g., valbenazine).

[0120] Nutritional active ingredients can be of the following types: vitamins (e.g., vitamins A, B, C, D, E, K, folic acid, biotin), minerals (e.g., potassium, chlorine, sodium, calcium, phosphorus, magnesium, iron, zinc, manganese, copper, iodine, chromium, molybdenum, selenium, cobalt, fluoride), amino acids, peptides, proteins 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 origin), fatty acids (e.g., omega-3, omega-6, omega-9 fatty acids), natural products produced using raw materials or substances extracted or derived from plants, animals, algae, fungi, lichens, or bacteria (phytosterols, echinacea, green tea extract, garlic, aloe vera, fish oil, spirulina, chlorella, mushroom-derived). digestive enzymes), sugars, polysaccharides (e.g., mannose, ribose, trehalose, dextrose, glucuronolactone, dextrin), probiotics (e.g., live microorganisms such as Lactobacillus, Bifidobacterium, Saccharomyces boulardii), prebiotics (e.g., fructans such as fructooligosaccharides and inulin, galactans such as galactooligosaccharides and xylooligosaccharides), antioxidants (e.g., lipoic acid, coenzyme Q10, flavonoids, glutathione, resveratrol, catechin), other substances with nutritional or physiological effects, e.g., betaine, caffeine, theobromine, theophylline, CDP-choline, choline, creatine, phospholipids, GABA, glucosamine, inositol, melatonin, methylsulfonylmethane, nucleotides, squalene)

[0121] Incorporation of the active ingredient into the electrospun fibers can be achieved by co-electrospinning the active ingredient with the biocompatible polymeric material, the facilitator, and the surfactant, if present. In this case, a mixture of the polymeric material to be electrospun, the electrospinning facilitator, and the active ingredient, optionally in the presence of the surfactant, can be prepared, and the resulting mixture is electrospun.

[0122] Alternatively, it is possible to first electrospin the biocompatible polymeric material, enhancer, and surfactant, and then incorporate the active ingredient into the resulting fiber. Depending on the application, it is also possible to provide that the active ingredient is absorbed into the electrospun fiber or entrapped in the resulting three-dimensional structure of the electrospun fiber.

[0123] For example, the electrospun compound can consist of a mixture of linear hyaluronic acid and cross-linked hyaluronic acid. The cross-linked hyaluronic acid increases the stiffness of the resulting nanometer fibers, but also increases the complexity of the three-dimensional structure of the resulting film obtained by successively depositing multiple layers of the resulting fibers. In particular, the presence of cross-linked hyaluronic acid causes the formation of cavities in the film, which can accommodate molecules of active ingredients.

[0124] According to another embodiment, the active ingredient is a non-steroidal anti-inflammatory agent, for example, for use in treating burns on the skin. One or more analgesics can also be added as additional active ingredients to relieve pain from burns. For this type of application, it is particularly advantageous for the biocompatible polymeric material to be of a skin-regenerating type, such as hyaluronic acid.

[0125] The article according to the present invention can be advantageously used for treating skin burns. It is advantageous because it allows the active ingredient and the first compound to be rapidly absorbed into the wound. Furthermore, the product obtained by electrospinning the composition can be applied directly to the burned area, thereby improving the therapeutic effect.

[0126] Advantageously, the active ingredient is present in a concentration of from 0.1 to 30% by weight, more preferably from 0.2 to 20% by weight, even more preferably from 0.5 to 10% by weight.

[0127] It should be noted that hyaluronic acid is a good candidate for electrospinning compounds in combination with several active ingredients from each of the three types listed above.

[0128] For example, cosmetic active ingredients can include antiseborrheic agents (sebacic acid, azelaic acid), antioxidants (ascorbic acid, tocopherol, retinol, retinal), anti-blemish agents (glabridin, ammonium persulfate), emollients (witch hazel extract, bisabolol), moisturizers (glycerin, propanediol, etc.), anti-wrinkle agents (e.g., aminobutyric acid), and one or more peptides and their metabolites and derivatives (e.g., essential fatty acids).

[0129] Among the preferred nutritional active ingredients are natural products (phytosterols, echinacea, green tea extract, garlic, aloe vera, fish oil, spirulina, chlorella, fungal digestive enzymes) made using intact sources or substances extracted or derived from plants, animals, algae, fungi, lichens, or bacteria, vitamins (e.g., vitamins A, B, C, D, E, K, folic acid, biotin), antioxidants (e.g., lipoic acid, coenzyme Q10, flavonoids, glutathione, resveratrol, catechins).

[0130] The most preferred active pharmaceutical 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), antiasthmatic combinations (e.g., dyphylline / guaifenesin), antibiotics (e.g., metronidazole), antibiotic / antineoplastic agents (e.g., doxorubicin), antineoplastic agents (e.g., isotretinoin), antineoplastic combinations (e.g., letrozole / ribociclib).

[0131] An example of a patch product includes a membrane substrate composed of electrospun fibers obtained from a composition containing sodium hyaluronate as a source of hyaluronic acid, pullulan as an electrospinning enhancer, mannitol, sodium surfactin as surfactants, aminobutyric acid, acetyl tetrapeptide-9, and acetyl tetrapeptide-11. Such a patch product is particularly suitable for application to facial skin, and is particularly suitable for skin rejuvenation.

[0132] It should be noted that such active ingredients may be advantageously combined with other compounds to be electrospun, such as, for example, xanthan gum, guar gum, chondroitin sulfate, collagen, starch, and the like.

[0133] Another example of a patch product is based on heparin as the electrospun compound and an active pharmaceutical ingredient, such as an allergen extract or a platelet stimulating agent like eltrombopag.

[0134] According to some embodiments, the patch product also contains a stabilizer, preferably a crosslinkable polymer. An example of a stabilizer is sodium alginate, which should be added to pullulan as a promoter. Preferably, the ratio of pullulan to alginate is 3:1.5 to 3:0.5, more preferably 3:1.

[0135] Once the article is made, it can be closed by placing a cover sheet over the base support. The cover sheet is attached to the base support by, for example, gluing or welding. This sheet can be made of the same material as the base support, or it can be made of another polysaccharide, another starch, or a material already known in the art, such as polybutylene succinate adipate (PBSA) or polylactic acid (PLA).

[0136] The article, i.e., the composite of film substrate and base support, can also be enclosed in a pouch of the familiar type made by welding two sheets of a heat-sealable material, such as PBSA or PLA, together to form a sealed interior space.

[0137] The items may be packaged in a secondary package, such as a box, which contains a number of pouches, each enclosing a respective item, as described above.

[0138] The use of this article serves as a preliminary step to moisturize the area of ​​skin to which the product is to be applied.Then, the pouch is opened, and the patch product is taken out, carefully touching only the polysaccharide support so as not to damage the film substrate.The patch product is then applied to the moisturized area of ​​the skin with the film substrate in direct contact with the skin.Due to the moisturizing effect of the polysaccharide support, the moisturizing effect of the film substrate, and the shape adaptability of the support, the film substrate is quickly and completely absorbed into the skin.The support is left on the skin for a few seconds, which is the time it takes for the absorption of the film substrate to be completed, and then it is peeled off.It should be noted that during this time, even for a short period of time, the polysaccharide support provides a moisturizing effect to the skin. [Example]

[0139] Thirty volunteers were asked to apply the cosmetic patch product of the present invention and a placebo and the results were evaluated.

[0140] Each volunteer applied both the cosmetic and a placebo to each arm, particularly the palm area of ​​the forearm, once a day for four months.

[0141] The cosmetics and placebo were placed on a non-genetically modified cornstarch-based support with a high amylose content, approximately 10 cm 2 The electrospun fibers were supplied in the form of sheets measuring 1000 x 1000 mm.

[0142] The cosmetic product used contained hyaluronic acid (HA) as the biocompatible polymer material to be electrospun and pullulan as the electrospinning enhancer. The electrospinning solution was prepared by dissolving 25 g of hyaluronic acid, 12.5 g of pullulan, and 1 g of biosurfactin in 30-50 mL of water, diluting to a volume of 100 mL, and controlling the pH to 5.5-6 by adding 1 M NaOH solution, if necessary.

[0143] The placebo contained only pullulan, without hyaluronic acid. As in the cosmetics section, 15 g of pullulan was dissolved in 30–50 mL of water, diluted to 100 mL, and the pH was adjusted to 5.5–6 with 1 M NaOH solution. The resulting solution was then electrospun.

[0144] The effects of the treatment were measured by instrumental methods, particularly assessing skin moisture, skin elasticity, and collagen density. Measurements were performed before the start of treatment (T0), and after 1 month (T1), 2 months (T2), and 3 months (T3) of treatment.

[0145] Skin moisture assessment Skin hydration was measured using a Courage+Khazaka Derma Unit SSC 3 device with the addition of a Corneometer® Hydration Probe. The probe consists of a series of gold-colored metal tracks that function as the plates of a capacitor. The plates are electrically isolated by an electrical insulator called a dielectric. When connected to a power source, electrons flow between the plates, creating an electric field. The amount of charge stored in a capacitor is called capacitance. Because most materials have a dielectric constant greater than that of a vacuum, any material between the capacitor plates increases its capacitance. Water content in the skin changes capacitance in proportion to its content, allowing skin hydration to be measured in arbitrary units.

[0146] Skin elasticity assessment Skin elasticity was measured using a Cortex DermaLab Combo Skinlab Elasticity Probe. This probe is equipped with a vacuum chamber, allowing suction to be applied to the skin surface. The suction method, which includes a skin elevation step and a skin retraction step, is controlled by an infrared sensor inside the probe chamber. One parameter related to skin elasticity is the "retraction time," which is the time, in milliseconds, required for the skin to retract 1.5 mm after being elevated to its maximum point. Young, elastic skin quickly returns to its initial state after lifting, while less elastic skin takes longer to retract. Therefore, a shorter retraction time indicates increased skin elasticity.

[0147] Assessment of collagen density High-resolution images of deep skin layers were obtained using the DermaLab Combo Skinlab ultrasound probe (Cortex). This technology is based on sending acoustic pulses of known frequencies into the skin itself and measuring the skin's acoustic response. These acoustic pulses strike various structures in the skin and are partially reflected. A portion of the reflected signal is picked up by the ultrasound transducer and processed to obtain a cross-sectional image of the skin. The intensity of the reflected signal is displayed on a color scale, with the darkest zones representing low-response zones (zones with low or no structure density) and lighter areas representing high-density zones. This technology allows for the reconstruction of images of the skin to a depth of 3.4 mm with a resolution of 0.06 mm, highlighting the structures of the epidermis, dermis, and subcutaneous layers. Image processing software provides values ​​for the intensity of the echo response, which directly correlate to collagen density. The acoustic pulses used are very low energy and do not adversely affect the skin or other tissues.

[0148] analysis Measurements were performed in a temperature-controlled environment of 21 ± 2°C and approximately 50% humidity. Before each measurement, volunteers were allowed to acclimate for 15 min.

[0149] To apply the cosmetics and placebo, moisten the skin according to the area to be treated, apply the product sheet with the base support facing up, moisten the skin and leave it to allow the product to adhere well to the skin, remove the base support, and gently tap the treatment area as needed to ensure complete absorption of the product.

[0150] result The treatment results for skin moisturization are summarized in Table 1 below and in the graph in Figure 1. Skin moisturization measurements are expressed in arbitrary corneometry units and are reported as the mean of the values ​​recorded during the study, the difference between the initial value (T0) and the values ​​recorded after 1 month (T1), 2 months (T2), and 3 months (T3), and as the percentage of change. An area of ​​skin that was not treated (with either cosmetic or placebo) was arbitrarily determined as the control zone.

[0151] [Table 1]

[0152] Cosmetic treatment significantly increased skin moisture by 6.8%, 18.9%, and 17.9% after 1, 2, and 3 months, respectively. No significant changes were observed in the placebo and control zones.

[0153] The results regarding skin elasticity are summarized in Table 2 and depicted graphically in Figure 2. Elasticity data are expressed in milliseconds (msec) and reported as the mean of the values ​​recorded during the study, the difference between the initial value (T0) and the values ​​recorded after 1 month (T1), 2 months (T2), and 3 months (T3), and as the percentage of change. An area of ​​skin that was not treated (with either cosmetic or placebo) was arbitrarily determined as the control zone.

[0154] [Table 2]

[0155] Cosmetic treatment resulted in a small but significant increase in skin elasticity of 3.7% and 3.8% after two and three months, respectively. Increases were also observed after one month, but were not significant. No significant increases in skin elasticity were observed in the placebo and control zones.

[0156] The collagen density results are summarized in Table 3 and graphed in Figure 3. Collagen density data are reported as the mean of the values ​​recorded during the study, the difference between the initial value (T0) and the values ​​recorded after 1 month (T1), 2 months (T2), and 3 months (T3), and as the percentage change. An area of ​​skin that was not treated (with either cosmetic or placebo) was arbitrarily determined as the control zone.

[0157] [Table 3]

[0158] Cosmetic treatment significantly increased collagen density after 1, 2, and 3 months by 18.4%, 29.1%, and 32.4%, respectively. No significant increase in skin elasticity was observed in the placebo and control zones.

[0159] Another study was conducted to evaluate the effect of cosmetics on collagen density. The application method was the same as that shown above, but treatment was administered over an 8-week period. Figures 4 and 5 show cross-sectional images of the skin of one of the volunteers, processed from data collected with the device used above. The white zones indicate the presence of collagen.

[0160] Figure 4 shows cross-sections of an area of ​​skin treated with cosmetic product at the start of treatment (T0, left) and after 1 month (T1), 2 months (T2) and 3 months (T3) of treatment. Figure 5 instead shows an area of ​​skin treated with placebo at the start of treatment (T0, left) and after 1 month (T1), 2 months (T2) and 3 months (T3) of treatment.

[0161] In cosmetically treated areas, there is a visible increase in skin collagen at the end of treatment, but this increase is not seen in untreated areas.

[0162] In conclusion, based on the studies reported above, it was found that continuous application of the cosmetic for three months significantly increased skin moisture by up to 18.9% in the first two months, with clearly visible results already visible one month after application, slightly but significantly increased skin elasticity by up to 3.7% and 3.8% after two and three months, and gradually and significantly increased collagen density by up to 32.4%, with effects already visible from the first month.

[0163] It will be apparent that modifications and / or additions of parts may be made to the articles and methods as hereinbefore described without departing from the field and scope of the present invention as defined by the claims.

[0164] It is also clear that although the present invention has been described with reference to some specific examples, a person skilled in the art can realize other equivalent forms of articles, including patch products, having the characteristics as set out in the claims and corresponding manufacturing methods, and therefore all fall within the field of protection defined thereby.

[0165] In the following claims, the sole purpose of reference signs in parentheses is to facilitate their reading and comprehension and they shall not be considered as limiting elements with regard to the field of protection defined by the same claims.

Claims

1. A patch product disposed on a base support, The patch product includes a skin-absorbable membrane substrate formed by at least one electrospun fiber composed of an electrospun first compound and an electrospinning enhancer; An article, wherein the base substrate comprises a polysaccharide-based biodegradable film that is not absorbed by the skin.

2. 2. The article according to claim 1, characterized in that the film that is not absorbed by the skin is starch-based, in particular corn starch-based.

3. 3. The article of claim 1 or 2, wherein the starch has an amylose concentration greater than 50% by weight relative to the weight of the starch.

4. 4. The article of claim 1, wherein the film has a thickness of less than 1 mm.

5. 5. The article of claim 1, wherein the 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, β-glucan, glycosaminoglycans, mucopolysaccharides, water-soluble polysaccharides, and derivatives thereof.

6. 6. The article of claim 5, wherein the electrospinning compound is selected from starch, elastin, hyaluronic acid, heparin, collagen, pectin, β-glucan, chondroitin sulfate, dermatan sulfate, heparan sulfate, and derivatives thereof.

7. 7. The article of claim 1, wherein the electrospinning facilitating agent is selected from alginates, pullulan, and mixtures thereof.

8. 8. The article according to any one of claims 1 to 7, characterized in that the membrane substrate also contains, as a surfactant, a lipopeptide obtained from the genus Bacillus.

9. 9. The article of claim 8, wherein the surfactant is selected from surfactin, pumilacidin, and lichenisin.

10. 10. An article according to any one of claims 1 to 9, characterized in that the membrane substrate also contains one or more active ingredients selected from peptides and their metabolites and derivatives.

11. 11. The article according to claim 10, characterized in that the one or more active ingredients are selected from tetrapeptides, in particular acetyl tetrapeptides.

12. 12. The article of claim 11, wherein the one or more active ingredients are selected from acetyl tetrapeptide-9, acetyl tetrapeptide-11, and mixtures thereof.

13. 1. A method for manufacturing an article comprising a patch product disposed on a base support, comprising: Electrospinning a composition comprising a first compound to be electrospun and an electrospinning facilitating agent to obtain electrospun fibers, wherein the electrospun fibers are directly deposited on the base support; The method according to claim 1, wherein the base support comprises a polysaccharide-based film that is not absorbed by the skin.

14. 14. The method according to claim 13, characterized in that the film that is not absorbed by the skin is starch-based, in particular corn starch-based.

15. 15. The method of claim 14, wherein the starch has an amylose concentration greater than 50% by weight based on the weight of the starch.

16. 16. The method of claim 13, 14 or 15, wherein the film has a thickness of less than 1 mm.

17. A primary packaging comprising a sealed pouch containing an article according to any one of claims 1 to 12.

18. 18. A primary package according to claim 17, characterized in that the pouch is made up of two heat-sealable sheets welded together by welding.

19. A secondary packaging body comprising a box containing a plurality of the primary packaging bodies according to claim 17 or 18.

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