Electrospinning composition
Patent Information
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2023-03-08
- Publication Date
- 2026-03-16
AI Technical Summary
Current electrospinning compositions face challenges in producing nanofibers on an industrial scale in water without affecting the environment, and they struggle to maintain consistent fiber diameters and prevent defects.
The composition includes a biocompatible polymer, a spinning accelerator, and a biosurfactant. The spinning accelerator stabilizes the electrospinning process, while the biosurfactant reduces surface tension and conductivity, enhancing discharge rates and preventing defects.
This composition allows for the production of continuous nanofibers with consistent diameters and high yields, maintaining ecological sustainability and improving industrial scalability.
Abstract
Description
[Technical field]
[0001] The present invention relates to an electrospinning composition, i.e. a composition that allows the production of nanofibers by electrospinning, more particularly to a type based on electrospun polymers, preferably biocompatible polymers. [Background technology]
[0002] Electrospinning processes are known that allow the production of nanofibers, i.e. continuous fibers with diameters on the order of nanometers, by subjecting compositions based on electrospinning polymer compounds to an electric field. Depending on the type of electrospinning compound, the resulting nanofibers can be applied in a variety of industries, for example in the medical, military defense, environmental, biotechnology, energy and cosmetic industries.
[0003] For environmental reasons, electrospinning tends to be carried out in environmentally friendly solvents, especially water. However, electrospinning of polymers in pure water is not straightforward due to its surface tension and the viscosity of the resulting compounds.
[0004] To overcome this problem, attempts have been made to reduce the surface tension and viscosity of water, for example by electrospinning in aqueous ammonium solutions, then in high pH solutions, and even in dimethylformamide (DMF)-containing water at 40°C. Tests have also been performed with hexafluoroisopropanol (HFIP) and ethanol. However, by doing so, the ecological aspect is lost.
[0005] Electrospinning compositions based on biocompatible polymers, which also contain electrospinning promoters, have been proposed that allow electrospinning in water. However, with the compositions described so far, the production of fibers on an industrial scale can be further improved, especially in terms of productivity.
[0006] Therefore, there is a need to develop an electrospinning composition that can overcome at least one of the shortcomings of the current state of the art.
[0007] For this purpose, it is necessary to solve the technical problem of electrospinning compositions that allow the electrospinning process to produce electrospun fibers on an industrial scale without impacting the environment.
[0008] In particular, one object of the present invention is to provide an electrospinning composition that can be electrospun in water with acceptable yields and on an industrial scale.
[0009] Another object of the present invention is to provide an electrospinning composition that allows for the production of continuous nanofibers, or at any rate fibers, of constant or nearly constant diameter and without defects.
[0010] Yet another object is to develop a method for preparing the above composition for electrospinning.
[0011] 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 objects and advantages. Summary of the Invention [Means for solving the problem]
[0012] The invention is set forth and characterized in the independent claims. The dependent claims describe further features of the invention or modifications to the main technical idea.
[0013] In accordance with the above objectives, in order to solve the above technical problems in a new and original way and to achieve considerable advantages compared to the current state of the art, the electrospinning composition according to the present invention comprises a first compound for electrospinning, a spinning promoter and a surfactant. The function of the spinning promoter is to facilitate the spinning of the first compound, in particular to stabilize the electrospinning process to obtain a certain fiber. The surfactant instead has the function of improving the electrospinning process to allow a higher discharge speed and thus obtain a higher yield, while avoiding the formation of defects in the fiber. This improvement is achieved by reducing the surface tension of the composition, which also reduces the electrical conductivity. In particular, it has been found that the surfactant makes it possible to avoid the phenomenon of dripping during electrospinning.
[0014] The first compound for electrospinning is a biocompatible polymer suitable for being electrospun 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, glycosaminoglycan, mucopolysaccharides, water-soluble polysaccharides and derivatives thereof.
[0015] Preferably, the cellulose derivative is selected from hydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose (HPC), hydroxyethylcellulose (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.
[0016] The spin enhancer is a polymeric carrier, possibly uncharged and selected from the group consisting of a second polysaccharide that is chemically different from the first polysaccharide, possibly together with poly(oxyethylene) (PEO). Advantageously, the polymeric carrier, although possibly uncharged, is biocompatible.
[0017] Preferably, the electrospinning enhancer is selected from pullulan and alginate, possibly mixed with poly(oxyethylene). The enhancer may consist of a mixture of pullulan and alginate. More preferably, the enhancer is chemically different from the first compound for electrospinning, i.e. the first compound for electrospinning is not pullulan or alginate.
[0018] The surfactant is preferably a biosurfactant, i.e. a surfactant of biological and organic origin, in particular obtained by fermentation of gram-positive bacteria, and such surfactants are biocompatible due to their biological origin.
[0019] Preferably, the surfactant is chosen among lipopeptides, in particular those obtained from the genus Bacillus.More preferably, the surfactant is chosen from the surfactin family, in particular from the group consisting of surfactin, pumilacidin and lichenisin.
[0020] Preferably, the surfactant is present at a concentration of 0.1 to 5% by weight, more preferably 0.2 to 2% by weight, and even more preferably 0.5 to 1% by weight, based on the total weight of the composition.
[0021] According to an embodiment, the pH of the composition is maintained at a slightly basic value, in particular between 6 and 7. To achieve this, it is preferable to add a basic compound to the composition, for example NaOH.
[0022] According to an embodiment, the composition also comprises an active ingredient, which may be selected, for example, from cosmetic active ingredients, pharmaceutical active ingredients and nutritional active ingredients.
[0023] According to an embodiment, the composition also comprises a stabilizer suitable for improving the stability of the fibers obtained after electrospinning. Preferably, the stabilizer is a crosslinkable polymer.
[0024] The advantage of the above composition lies in the possibility of creating cosmetic, pharmaceutical or nutritional products based on natural polymers with much higher local concentrations of the target compound than can be obtained with conventional formulations. This is due to the precise incorporation of the target compound into the structure of the final product. With known compositions, it is virtually impossible to reach high concentrations, even with polysaccharides, collagen, gelatin, albumin, elastin and their low molecular weight derivatives, since the viscosity of the product becomes too high and cannot exceed 5-10% by weight. With the present composition, it is possible to obtain applicable products with a concentration of the target compound up to 50% by weight.
[0025] It should be noted that, depending on the electrospun compound and depending on the active ingredient, different types of use can be envisaged for the composition according to the invention, in particular for use in the cosmetic, pharmaceutical or nutritional industry. More precisely, cosmetic applications can provide for topical skin applications as described above, while pharmaceutical and nutritional applications can instead provide for the release of active ingredients, drugs and / or supplements in the body.
[0026] According to one aspect, a method of preparing an electrospinning composition is also provided, in which a first compound for electrospinning, a spin enhancer, and a surfactant are mixed.
[0027] The first compound for electrospinning is a biocompatible polymer suitable for being electrospun and is selected from the group consisting of a first polysaccharide, collagen, albumin, gelatin, 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, β-glucan, glycosaminoglycan, mucopolysaccharides, water-soluble polysaccharides and derivatives thereof. Preferably, the cellulose derivative is selected from hydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose (HPC), hydroxyethylcellulose (HEC), sodium carboxymethylcellulose (Na-CMC). The glycosaminoglycan (GAG) or mucopolysaccharide may be selected from chondroitin sulfate, dermatan sulfate, heparin, heparan sulfate and hyaluronic acid (HA). The water soluble polysaccharides may be selected from galactomannan, xylan, gum arabic, gum ghatti, glucomannan, acemannan, water soluble dietary fibre, glycogen, amylose and polysaccharides of plant, bacterial and fungal origin.
[0028] The spin enhancer is an uncharged polymeric carrier selected from the group consisting of a second polysaccharide that is chemically different from the first polysaccharide, possibly together with poly(oxyethylene) (PEO). Preferably, the uncharged polymeric carrier is also biocompatible. Preferably, the second polysaccharide of the composition is selected from alginate and pullulan.
[0029] Surfactants are biosurfactants, i.e. surfactants of biological and organic origin. In particular, biosurfactants are obtained by fermentation of gram-positive bacteria. As such surfactants are of biological origin, they are biocompatible.
[0030] Preferably, the surfactant is selected from among lipopeptides, especially those obtained from the genus Bacillus. More preferably, the surfactant is selected from the surfactin family, especially the group consisting of surfactin, pumilacidin and lichenisin.
[0031] According to an embodiment, the method includes adding a surfactant before starting electrospinning of the composition to stabilize the production. For example, the method can include dissolving the first compound, the electrospinning facilitator and the surfactant in water, preferably in separate aliquots of water, and mixing them.
[0032] According to an embodiment, the method envisages maintaining the pH of the composition at a slightly basic value, i.e. between 6 and 7, by the addition of a basic compound. The addition may be any base, for example NaOH.
[0033] According to an embodiment, the method comprises adding an active ingredient, which may be selected, for example, from cosmetic active ingredients, pharmaceutical active ingredients and nutritional active ingredients.
[0034] According to an embodiment, the method also provides for adding a stabilizing agent suitable for improving the stability of the fibers obtained after electrospinning. Preferably, the stabilizing agent is a crosslinkable polymer.
[0035] According to another aspect, a patch product is provided that is preferentially applied to the skin and is composed of a membrane substrate that can be absorbed by the skin. The membrane substrate is electrospun. The electrospun membrane substrate is composed of at least one fiber, preferably nanofiber, in particular in the form of a nonwoven fabric.
[0036] At least one of the fibers forming the membrane substrate also comprises a first electrospinning compound, an electrospinning facilitator, and a surfactant, these compounds being of the type defined above in the Compositions and Methods.
[0037] According to an embodiment, the fibers have a flattened shape, i.e. a flat cross section. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0038] Unless otherwise defined, all technical and scientific terms used herein and hereinafter have the same meaning as commonly understood by those skilled in the art to which this invention belongs. Methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, which methods and materials are described below as examples. 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.
[0039] All measurements were made at 25°C (room temperature) and atmospheric pressure unless otherwise noted. All temperatures are in degrees Celsius unless otherwise noted.
[0040] All percentages and ratios given are intended to indicate weight (w / w) of the total composition unless otherwise specified.
[0041] Percentage ranges provided herein are assumed to total 100% for all components unless otherwise noted.
[0042] All ranges set forth herein are intended to include the extreme values as well as convey a range "between" two values, unless otherwise specified.
[0043] The present disclosure also includes ranges resulting from the overlap or joining of two or more disclosed ranges, unless specifically stated otherwise.
[0044] The present disclosure also includes ranges that may result from combinations of two or more disclosed point values, unless otherwise stated.
[0045] Where water is listed, it is distilled water unless otherwise noted.
[0046] The composition comprises a first compound for electrospinning which is a biocompatible polymer suitable for electrospinning and is selected from 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, fungi, and derivatives thereof.
[0047] Such compounds or classes of compounds have the property of being able to modify the viscosity of the liquid, are suitable for forming certain electrospun fibers with good mechanical and absorption properties, and are all biocompatible, naturally occurring, and can be used in the food, pharmaceutical and / or cosmetic industries.
[0048] In particular, xanthan gum, dextran, carrageenan, Na-CMC, starch, gelatin and ghatti gum are used as thickeners, stabilizers and sometimes gelling agents in the food industry. Furthermore, xanthan gum is used as a stabilizer for suspensions and emulsions in the pharmaceutical and cosmetic industries, guar gum is used as a thickener and gelling agent in the pharmaceutical and cosmetic industries, and carrageenan is used as an inert excipient in the pharmaceutical industry. Dextran is also used as a thickener in the pharmaceutical industry.
[0049] Chitosan is used in the food industry in low-calorie diets and in the pharmaceutical industry as an excipient, especially in inhalation products, while pectin is used in the food industry as a gelling agent and in the pharmaceutical industry as a nutritional supplement and probiotic.
[0050] Agar, galactomannan and glucomannan are used as gelling agents in the nutritional industry.
[0051] 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 medicines 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.
[0052] Beta-glucans, like xylans, are used as dietary fiber. Chondroitin sulfate is used as a dietary supplement and to treat osteoarthritis. Dermatan sulfate, heparin, and heparan sulfate are known in the pharmaceutical industry as anticoagulants.
[0053] Gum arabic is used in the food industry as a stabilizing excipient and viscosity modifier. Acemannan is known in the pharmaceutical industry for its immunostimulatory properties.
[0054] It should be noted that some of these compounds have unique functions in the cosmetic, pharmaceutical or food industry, such as starch, elastin, hyaluronic acid, heparin, collagen, pectin, β-glucan, chondroitin sulfate, dermatan sulfate, heparan sulfate and their derivatives. Therefore, it is advantageous to electrospin these compounds, because by applying the corresponding fibers, these compounds can be applied in higher doses than known solutions, resulting in a higher effect.
[0055] When the first compound for electrospinning is hyaluronic acid, it can be linear or crosslinked, with a high molecular weight, for example, 1 million daltons or more, or with a low molecular weight, typically 10,000 daltons or less. It is also possible to provide a mixture of linear and crosslinked hyaluronic acid, which allows the stiffness of the resulting spun yarn and the three-dimensional structure of the film obtained by depositing the spun yarn on a support to be adjusted.
[0056] The first compound is advantageously diluted in water or a water-based solution, for example at a concentration of 0.1-30% by weight, preferably 1-20% by weight, more preferably 5-15% by weight.
[0057] The electrospinning composition also contains a spinning aid, which is a biocompatible, uncharged polymeric carrier, selected from alginate, possibly with PEO, or pullulan, preferably pullulan, as this gives the best results.
[0058] When alginate is mixed with PEO, they can be diluted separately in water or a water-based solution at a concentration of 0.1-30% by weight, preferably 1-20% by weight, more preferably 5-15% by weight. Alginate:PEO mixtures, when the latter is present, are preferably produced in weight ratios ranging from 5:1 to 1:5, more preferably 2:1 to 1:2. The best electrospinning results were obtained with a ratio equal to 1:1 by weight.
[0059] Pullulan may be diluted in a water-based or aqueous solution, preferably at a concentration of 0.1-30% by weight, preferably 1-20% by weight, more preferably 5-15% by weight.
[0060] The first compound and accelerator for electrospinning 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 are obtained with a composition having a weight ratio of first compound:accelerator of 1:1.
[0061] The composition also includes a surfactant, which is selected from biosurfactants, ie, surfactants of biological and organic origin, as opposed to bacterially derived surfactants.
[0062] In particular, the surfactant of the composition is advantageously obtained by fermentation of a gram-positive bacterium.
[0063] More precisely, the biosurfactant is chosen from lipopeptides, in particular those derived from the fermentation of organisms of the Bacillus genus, more particularly those with a low molecular weight, for example those whose molecular weight is at most 10 000 g / mol, preferably at most 5 000 g / mol and more preferably at most 2 500 g / mol.
[0064] Among these lipopeptides, there are several families, such as surfactins, iturins, fengycins, crustatins, rocillomycins, etc. 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 chains, but all have surfactant properties.
[0065] Preferably, the biosurfactant of the composition is selected from the family of surfactins.
[0066] The surfactin family includes surfactin itself, which is produced by various branches of the Bacillus genus, especially B. subtilis, but also by other branches such as B. natto and B. circulans. Its structure consists of 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, L-Leu, the first and last amino acids are linked by an ester bond to form a lactone ring). Surfactins have a β-hydroxy fatty acid chain with 13 to 16 carbon atoms. More than 30 congeners of surfactin are known, but all have the same chiral sequence of amino acids in the lactone ring, LLDLLDL. Congeners are molecules of the same genus, but are not isomers.
[0067] The surfactin family also includes pumilacidins, which are derived from the variant AF of the B. pumilus branch. Compared to surfactin, the amino acid at position 7 is substituted with L-Val or L-Ile.
[0068] The surfactin family ultimately includes lichenisins, obtained primarily from B. licheniformis, which differ from surfactins in that position 1 of the lactone ring of L-glutamic acid is replaced by L-glutamine.
[0069] Surfactin, pumilacidin and lichenisin contain five hydrophobic residues (Leu, Val or Ile) and long secondary aliphatic chains, and have strong surface active properties. In fact, it has been confirmed that highly purified surfactin family compounds can reduce the surface tension of water from 72 mN / m to 27 mN / m at a concentration of 0.0005 wt%. Surfactin is particularly suitable for electrospinning in aqueous solutions, since it is stable and soluble in water over a wide pH range (5-13) and temperature.
[0070] Preferably, the biosurfactant is surfactin. In particular, surfactin or biosurfactin has a solubility in water at 20° C. of 548 g / L, a critical micelle concentration (CMC) of 0.0003 wt%, a hydrophilic to hydrophobic ratio (HLB) of 10-17, more preferably 15.9-16.5 (taking into account the carbon chain of a β-hydroxy fatty acid of length C13-C15) or 10-12, a critical packing parameter (CPP) of less than 0.33, more preferably 0.12-0.16, and / or a pKa value of 4.271-3.727.
[0071] It should be noted that the above HLB values are calculated using the Griffin method.
[0072] Generally, the biosurfactant will be present at a concentration of less than 5% by weight, preferably less than 2% by weight, more preferably from 0.5 to 1% by weight of the composition.
[0073] The composition also comprises at least one active ingredient of pharmaceutical, nutritional and / or cosmetic type.
[0074] It should be noted that an active ingredient can have different types of functions, regardless of its field of action.
[0075] Cosmetic active ingredients can be of the following types: antiseborrheic agents (e.g., sebacic acid, azelaic acid), antisebum agents (e.g., charcoal powder), 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), cleaning agents (e.g., sodium cocoyl glutamate), deodorants (e.g., triethyl citrate, zinc ricinoleate), scrubbing agents (e.g., glycolic 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), perfumes (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 oil), soothing agents (e.g. witch hazel extract, chamomile extract, bisabolol) or tonics (e.g. arnica montana, capsicum extract), UV filters (e.g. methylene bisbenzotriazolyl tetramethylbutylphenol, ethylhexyl methoxycinnamate, caffeine, theine, theobromine, theophylline).
[0076] 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 antagonists (e.g., amlodipine / benazepril), ACE inhibitors with thiazides (e.g., hydrochlorothiazide), adamantane antiviral drugs (e.g., amantadine), adrenal corticosteroid inhibitors (e.g., aminoglutethimide), adrenergic bronchodilators (e.g., albuterol), hypertensive emergency medications (e.g., diazoxide), pulmonary hypertension drugs (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), amebicide (e.g., metronidazole), aminoglycosides (e.g., tobramycin), aminopenicillins (e.g., amoxicillin), aminosalicylates (e.g., aminosalicylic acid), AMPA receptor antagonists (e.g., penicillin), rampanel), amylin analogues (e.g., pramlintide), analgesics (e.g., acetaminophen), androgenic and anabolic steroids (e.g., testosterone), angiotensin-converting enzyme inhibitors (e.g., ramipril), angiotensin II inhibitors with calcium channel antagonists (e.g., amlodipine / olmesartan), angiotensin II inhibitors with thiazides (e.g., hydrochlorothiazide / olmesartan), angiotensin receptor blockers (e.g., valsartan), angiotensin and neprilysin receptor antagonist inhibitors (e.g., sacubitril / valsartan), anorectal medications (e.g., hydrocortisone / pramoxine), appetite suppressants (e.g., phentermine), antacids (e.g., magnesium hydroxide), anthelmintics (e.g., pyrantel), antiangiogenic eye drops (e.g., aflibercept), anti-CTLA-4 monoclonal antibodies (e.g., ipilimumab), monoclonal anti-PD-1 antibodies (e.g., nivolumab), thiazide-containing (central) antiadrenergics (e.g., hydrochlorothiazide / methyldopa),Thiazide-containing (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), e.g. 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), for example anticholinergic / antispasmodics (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), antigonadotropic hormones (e.g. danazol), antigout drugs (e.g. colchicine), antihistamines (e.g. cetirizine), antihyperlipidemic drugs, and Combinations thereof (e.g., ezetimibe / simvastatin), antihyperuricemia drugs (e.g., febuxostat), antimalarials (e.g., doxycycline), combination antimalarials, antimalarial quinolinic drugs (e.g., hydroxychloroquine), antimanic drugs (e.g., lithium), metabolic antagonists (e.g., capecitabine), antimigraine drugs (e.g., rizatriptan), antineoplastic drugs (e.g., isotretinoin), combination antineoplastic drugs (e.g., letrozole / ribociclib), antineoplastic antidotes (e.g., amifostine), antineoplastic interferon drugs (e.g., indole), terferon α-2b), antipseudomonal penicillins (e.g., carbenicillin), antipsoriatics (e.g., acitretin), antipsychotics (e.g., haloperidol), antirheumatics (e.g., adalimumab), antiseptics and disinfectants, antithyroid drugs (e.g., potassium iodide), antitoxins and antivirals (e.g., polyvalent antivenom (viper)), antitussives (e.g., dextromethorphan), antiviral boosters (e.g., ritonavir), antiviral interferons (e.g., peginterferon 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), anticonvulsants Barbiturates (e.g., primidone), barbiturates (e.g., phenobarbital), BCR-ABL tyrosine kinase inhibitors (e.g., imatinib), anticonvulsants 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., colsevelam), bisphosphonates (e.g., zoledronic acid), BTK inhibitors (e.g., ibrutinib), calcium receptor agonists (e.g., cinacalcet), calcineurin inhibitors (e.g., tacrolimus), calcitonin, calcium channel antagonists (e.g., verapamil), carbamate anticonvulsants (e.g., felbamate), carbapenems (e.g., doripenem), carbapenem / β-lactamase inhibitors (e.g., meropenem / vaborbactam), anticonvulsants Carbonic anhydrase inhibitors (e.g., Topiramate), carbonic anhydrase inhibitors (e.g., acetazolamide), regenosidase stress drugs, β-cardiac selective β-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, anti-CD52 monoclonal antibodies (e.g., alemtuzumab), CDK4 / 6 inhibitors (e.g., palbociclib), cephalosporins Phosphate / β-lactamase inhibitors (e.g., avibactam / ceftazidime), ceruminoleptics (e.g., urea peroxide), CFTR combination drugs (e.g., ivacaftor / lumacaftor), CFTR enhancers (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), corticotropins, coumarins and indandione (e.g. warfarin), cox-2 inhibitors (e.g. celecoxib), decongestants (e.g. pseudoephedrine), diarylquinolines (e.g. ), anticonvulsants dibenzazepines (e.g. carbamazepine), digestive enzymes (e.g. lactase), dipeptidyl peptidase 4 inhibitors drugs (e.g. sitagliptin), dopaminergic antiparkinson 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), anticonvulsant fatty acid derivatives (e.g. divalproex sodium), fibric acid derivatives (e.g. phenobarbital), fibrates), first generation cephalosporins (e.g., cephalexin), fourth generation 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), antibiotics (e.g., vancomycin), platelet glycoprotein inhibitors (e.g., tirofiban), glucagon inhibitors (e.g., cephalosporins), cephalosporins ... Lysylcyclines (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), H2 antagonists (e.g., ranitidine), Helicobacter pylori eradication drugs (e.g., bismuth subcitrate potassium / metronidazole / tetracycline), hedgehog pathway inhibitors (e.g., vismodegib), heparin antagonists (e.g., protamine), HER2 inhibitors (e.g., neratinib), herbal products (e.g., 5-hydroxytryptophan, aloe vera), histone deacetylase inhibitors (e.g., romidepsin), hormones / antineoplastic agents (e.g., metoprolol), proxyprogesterone), 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., ferrous sulfate), 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), methylxanes steroids (e.g., theocorticoids), mineralocorticoids (e.g., fludrocortisone), minerals and electrolytes (e.g., citric acid / potassium citrate), various antiviral drugs (e.g., baloxavir marboxil), various anxiolytics, sedatives, and 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 drugs (e.g., misoprostol), various metabolic drugs (e.g., burosumab), various respiratory drugs (e.g., α1-proteinase inhibitors), various topical drugs (e.g., sodium hyaluronate), various vaginal drugs (e.g., estradiol), mitotic inhibitors (e.g., vincristine), monoamine oxidase inhibitors (e.g., phenelzine), pharyngeal and oral products (e.g., fluorides), MTOR inhibitors (e.g., everolimus), mucolytics (e.g., acetylcysteine), multitinase 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-cardiac selective beta blockers (e.g., carvedilol), non-sulfonylurea drugs (e.g., metformin), Nonsteroidal anti-inflammatory drugs (e.g., diclofenac), NS5A inhibitors (e.g., daclatasvir), nucleoside reverse transcriptase inhibitors (NRTIs) (e.g., tenofovir), nutritional supplements (e.g., omega-3 polyunsaturated fatty acids), oral nutritional supplements (e.g., arginine), other immunostimulants (e.g., glatiramer), other immunosuppressants (e.g., omalizumab), anticonvulsants oxazomib Zolidinediones (e.g., trimethadione), antibiotic oxazolidineones (e.g., linezolid), parathormone and analogues (e.g., teriparatide), PARP inhibitors (e.g., niraparib), PCSK9 inhibitors (e.g., evolocumab), penicillinase-resistant penicillins (e.g., oxacillin), peripheral opioid receptor antagonists (e.g., naloxegol), mixed peripheral opioid receptor antagonists (e.g., eluxadoline), agonists / antagonists), 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), progesterone receptor modulators (e.g., ulipristal), progestins (e.g., 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., ophthalmidine), meprazole), psoralens (e.g., methoxsalen), purine nucleosides (e.g., valacyclovir), pyrrolidine anticonvulsants (e.g., levetiracetam), quinolones (e.g., ciprofloxacin), recombinant 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 receptor selective), modulators (e.g., ospemifene), selective immunosuppressants (e.g., , natalizumab), selective phosphodiesterase-4 inhibitors (e.g., roflumilast), selective serotonin reuptake inhibitors (e.g., escitalopram), serotonin-norepinephrine reuptake inhibitors (e.g., duloxetine), serotonergic enteric neuromodulators (e.g., tegaserod), SGLT2 inhibitors (e.g., empagliflozin), skeletal muscle relaxants (e.g., onabotulinumtoxin-A), smoking cessation aids (e.g., nicotine analogues somatostatin) (e.g., octreotide), statins (e.g., lovastatin), streptogramins (e.g. dalfopristin / quinupristin), Streptomyces derivatives (e.g. capreomycin), anticonvulsants succinamides (e.g. ethosuximide), sulfonamides (e.g. sulfamethoxazole), psychostimulants sulfonylureas (e.g. glimepiride, 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., dabigatazone), streptococcal agents (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., ecoxin), topical antihistamines (e.g., diphenhydramine), topical antineoplastics (e.g., imiquimod), topical antipsoriatics (e.g., tazarotene), topical antivirals (e.g., penciclovir), topical astringents (e.g., hazelnut), topical exfoliants (e.g., collagenase), topical bleaching agents (e.g., hydroquinone), topical emollients (e.g., emollients), topical keratolytics (e.g., salicylic acid), topical nonsteroidal anti-inflammatory agents (e.g., diclofenac), topical photochemotherapy (e.g., psoriasis), topical dermatological agents ... medications (e.g., aminolevulinic acid), topical rubefacients (e.g., menthol), 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 ( For example, amitriptyline), regulators (for example, potassium citrate), uterotonics (for example, dinoprostone), bacterial vaginosis drugs (for example, clindamycin), vasodilators (for example, alprostadil), vasopressin antagonists (for example, conivaptan), vasoconstrictors (for example, epinephrine), VEGF / VEGFR inhibitors (for example, pazopanib), viral vaccines, vitamin / mineral combinations, vitamins (for example, cyanocobalamin), VMAT2 inhibitors (for example, valbenazine).
[0077] Nutritional active ingredients are of the vitamin type (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, animal or vegetable dietary proteins), fatty acids (e.g. omega-3, omega-6, omega-9 fatty acids), natural products produced using raw materials or extracted or derived from plants, animals, algae, fungi, lichens or bacteria (phytosterols, echinacea, green tea extract, garlic, aloe vera, fish oil, spirulina, chlorella, digestive tract from fungi). enzymes, sugars, polysaccharides (e.g. mannose, ribose, trehalose, dextrose, glucuronolactone, dextrin), probiotics (e.g. live microorganisms such as Lactobacillus, Bifidobacterium, Saccharomyces boulardii, etc.), prebiotics (e.g. fructans such as fructooligosaccharides and inulin, galactans such as galactooligosaccharides and xylooligosaccharides, etc.), antioxidants (e.g. lipoic acid, coenzyme Q10, flavonoids, glutathione, resveratrol, catechins), 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).
[0078] The inclusion of the active ingredient in the electrospun fibers can be achieved by electrospinning the active ingredient together with the first compound, in which case a mixture of the first compound for electrospinning, the electrospinning promoter, and the active ingredient can be prepared, and the resulting mixture is electrospun.
[0079] Alternatively, it is envisaged to electrospin only the first compound and then incorporate the active ingredient into the resulting fibre. Depending on the application, it is expected that the active ingredient will be absorbed into the electrospun fibre or entrapped in the three-dimensional structure obtained with the electrospun fibre.
[0080] For example, the first compound for electrospinning may consist of a mixture of linear and cross-linked hyaluronic acid. The cross-linked hyaluronic acid has the effect of increasing the stiffness of the resulting nanometric fibers, but also of increasing the complexity of the three-dimensional structure of the film obtained by successively depositing the resulting fibers in several layers. In particular, the presence of cross-linked hyaluronic acid causes the formation of cavities in the film, which allow the cavities to accommodate molecules of the active ingredient.
[0081] According to another embodiment, the active ingredient is a non-steroidal anti-inflammatory agent, for example, applied to skin burns.Also, one or more analgesics can be added as additional active ingredients to relieve pain caused by burns.For this type of application, it is particularly advantageous that the first compound is a skin regenerating type, such as hyaluronic acid.
[0082] The use of the composition according to the present invention in the treatment of skin burns is beneficial because it provides the active ingredient and the first compound to be absorbed quickly into the wound.Furthermore, the product obtained by electrospinning the composition can be directly applied to the burned area, which improves the therapeutic effect.
[0083] Advantageously, the active ingredient is present in a concentration ranging 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.
[0084] It should be noted that hyaluronic acid is a good candidate for combining with the three different types of active ingredients listed above as a compound for electrospinning.
[0085] For example, cosmetic active ingredients can include antiseborrheic agents (sebacic acid, azelaic acid), antioxidants (ascorbic acid, tocopherol, retinol, retinal), anti-spot agents (glabridin, ammonium persulfate), emollients (witch hazel extract, bisabolol), and moisturizers (glycerin, propanediol, etc.).
[0086] Among the preferred nutritional active ingredients are natural products (phytosterols, echinacea, green tea extract, garlic, aloe vera, fish oil, spirulina, chlorella, digestive enzymes from fungi), vitamins (e.g., vitamins A, B, C, D, E, K, folic acid, biotin), antioxidants (e.g., lipoic acid, coenzyme Q10, flavonoids, glutathione, resveratrol, catechin) produced from intact sources or using substances extracted or derived from plants, animals, algae, fungi, lichens, or bacteria.
[0087] The most preferred medicament active substances are androgens and anabolic steroids (e.g. testosterone), anti-CTLA-4 monoclonal antibodies (e.g. ipilimumab), anti-PD-1 monoclonal antibodies (e.g. nivolumab), anti-anginal drugs (e.g. nitroglycerin), anti-asthmatic combinations (e.g. dyphylline / guaifenesin), antibiotics (e.g. metronidazole), antibiotics / antineoplastic drugs (e.g. doxorubicin), antineoplastic drugs (e.g. isotretinoin), antineoplastic combinations (e.g. letrozole / ribociclib).
[0088] 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.
[0089] Another example of a composition is heparin as a compound for electrospinning and an active pharmaceutical ingredient, for example an allergen extract or a platelet stimulating agent such as eltrombopag.
[0090] According to an embodiment, the composition also contains a stabilizer, which is 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:alginate is 3:1.5 to 3:0.5, more preferably 3:1.
[0091] This application also intends to protect the method for preparing the composition described above, said process providing for mixing the components of the composition together in water or an aqueous solution. It may provide for mixing all the components simultaneously or adding them one after the other. It may also be possible to dissolve each component separately in an aliquot of water and then mix the aliquots to obtain the composition, or an aliquot of one or two components.
[0092] The surfactant is preferably added some time before electrospinning to make the electrospinning more stable, resulting in more consistent and defect-free electrospun fibers.
[0093] Electrospinning the composition according to the above method results in the realization of one or more electrospun fibers, in particular nanofibers, that form a membrane substrate. Such a membrane substrate may be in the form of a nonwoven fabric.
[0094] The fibers produced are substantially composed of the compounds of the composition described above. In particular, the fibers are composed of a first compound for electrospinning, an electrospinning facilitator and a surfactant. If provided in the composition, the fibers also include an active ingredient and / or a stabilizer.
[0095] With particular reference to active ingredients, it should be noted that the active ingredient may be electrospun with the remainder of the composition, resulting in it being integrated into the fiber, or it may be separate from the fiber and inserted into the membrane substrate.
[0096] Electrospun fibers have been observed to have a flat ribbon shape, i.e., a flat or oblate cross section. EXAMPLES
[0097] The following compositions were electrospinned using industrial equipment:
[0098] [Table 1]
[0099] The composition was prepared by dissolving hyaluronic acid in 100 g water, pullulan in 100 g water, and the surfactant and base in 36.5 g water.
[0100] Three aliquots of water containing each component were mixed and the resulting solution was loaded into an industrial device. An A4 size fiber layer could be produced in 2 hours. The resulting fibers were observed to be uniform, defect-free, and substantially ribbon-shaped, i.e., with a flat or flattened cross section.
[0101] It will be apparent that modifications and / or additions of parts or steps may be made to the compositions and preparation methods as hereinbefore described without departing from the field and scope of the present invention as defined by the claims.
[0102] Furthermore, although the present invention has been described with reference to some specific examples, it is clear that a person skilled in the art can certainly realize other equivalent forms of electrospinning compositions having the properties as described in the claims, and therefore can realize everything that falls within the scope of protection defined by the claims.
Claims
1. A first compound for electrospinning selected from xanthan gum, pectin, chitin, chitosan, dextran, carrageenan, guar gum, agar, cellulose derivatives, albumin, starch, gelatin, collagen, elastin, β-glucan, glycosaminoglycan, mucopolysaccharides, water-soluble polysaccharides and their derivatives, The electrospinning accelerator comprises alginates, pullulan, and mixtures thereof, An electrospinning composition characterized by containing biological and organic surfactants obtained by fermentation of Gram-positive bacteria.
2. The electrospinning composition according to claim 1, characterized in that the surfactant is a lipopeptide obtained by a Bacillus species.
3. The electrospinning composition according to claim 2, characterized in that the surfactant is selected from surfactin, pumiracidine, and lichenisin.
4. The electrospinning composition according to claim 1, characterized in that the surfactant is present in a concentration of 0.1 to 5% by weight relative to the total weight of the electrospinning composition.
5. The electrospinning composition according to claim 4, characterized in that the pH is 6 to 7.
6. The electrospinning composition according to claim 5, characterized in that it contains a basic compound at a concentration of less than 2% by weight relative to the total weight of the electrospinning composition.
7. The electrospinning composition according to any one of claims 1 to 6, characterized in that the weight ratio of the first compound for electrospinning to the electrospinning accelerator is between 2:1 and 1:
2.
8. The process includes the step of mixing a first compound for electrospinning with an electrospinning accelerator and a surfactant. The first compound for electrospinning is selected from xanthan gum, pectin, chitin, chitosan, dextran, carrageenan, guar gum, agar, cellulose derivatives, albumin, starch, gelatin, collagen, elastin, β-glucan, glycosaminoglycan, mucopolysaccharides, water-soluble polysaccharides and their derivatives. The electrospinning accelerator is selected from alginates, pullulan, and mixtures thereof. A method for preparing an electrospinning composition, wherein the surfactant is of biological and organic origin obtained by fermentation of Gram-positive bacteria.
9. The method according to claim 8, characterized in that the surfactant is a lipopeptide obtained by a Bacillus species.
10. The method according to claim 9, characterized in that the surfactant is selected from surfactin, pumiracidine, and lichenisin.
11. The method according to claim 8, characterized in that the first compound for electrospinning, the electrospinning accelerator, and the surfactant are each mixed in separate aliquots of water, and then the aliquots of water are combined.
12. The method according to any one of claims 8 to 11, characterized in that a basic compound is mixed with the first compound for electrospinning, the electrospinning accelerator, and the surfactant so as to maintain the pH of the mixture between 6 and 7.
13. It contains a membrane substrate that can be absorbed by the skin, The film substrate is formed by at least one electrospinning fiber based on a first compound for electrospinning, an electrospinning accelerator, and a surfactant. The first compound for electrospinning is selected from xanthan gum, pectin, chitin, chitosan, dextran, carrageenan, guar gum, agar, cellulose derivatives, albumin, starch, gelatin, collagen, elastin, β-glucan, glycosaminoglycan, mucopolysaccharides, water-soluble polysaccharides and their derivatives. The electrospinning accelerator is selected from alginates, pullulan, and mixtures thereof. The patch product is characterized in that the surfactant is of biological and organic origin, obtained by fermentation of Gram-positive bacteria.
14. The patch product according to claim 13, characterized in that the at least one electrospinning fiber has a flat, ribbon-like shape.
15. The patch product according to claim 13 or 14, characterized in that the surfactant is a lipopeptide obtained by a Bacillus species.
16. The patch product according to claim 15, characterized in that the surfactant is selected from surfactin, pumiracidine, and lichenicin.