Nanofiber-based skin patch for alleviating pain, swelling, and inflammation and fabrication method thereof

Abstract

A nanofiber-based skin patch for alleviating pain, swelling, and inflammation comprising a skin adhesive layer, a nanofibrous layer comprising at least one macromolecule and a composition of natural active agents comprising a mint extract, a rose madder extract, a rosemary extract, a lavender extract, a clove extract, an arnica extract, a ginger extract, a sage extract, a ginseng extract, a garlic extract, curcumin, bromelain, honey, royal jelly, propolis, a non-woven layer configure to connect the nanofibrous layer to the skin adhesive layer such that the nanofibrous scaffold is fabricated on a top surface of non-woven layer, and a protective layer configure to protect the nanofibrous layer. The developed nanofiber-based skin patch can relieve pain, reduce swelling, and mitigate inflammation in different areas of a subject's bod without causing side effects.

Description

NANOFIBER-BASED SKIN PATCH FOR ALLEVIATING PAIN, SWELLING, AND INFLAMMATION AND FABRICATION METHOD THEREOFCROSS REFERENCE TO RELATED APPLICATION

[0001] This application claims the benefit of priority from US Provisional Application No. 63 / 617,084, filed on January 3, 2024, entitled “HERBAL NANOFIBER SKIN PATCHES FOR USE IN DIFFERENT PARTS OF THE BODY”, which is incorporated herein by reference in its entirety.TECHNICAL FIELD

[0002] The present disclosure is generally related to an exemplary nanofiber-based skin patch for alleviating pain, swelling, and inflammation, more particularly to an exemplary nanofiber-based skin patch comprising a nanofibrous layer comprising a plurality of natural active agents for alleviating pain, swelling, and inflammation, and a fabrication method thereof.BACKGROUND

[0003] Pain, swelling, and inflammation are inherent physiological responses that arise from physical injuries, such as wounds and trauma, and / or occur during the progression of various illnesses and surgical procedures, and persist throughout the post-operative period and the recovery phase. Patients frequently seek effective solutions to manage and alleviate clinical symptoms such as pain, swelling, and inflammation. In many cases, this involves the use of a plurality of painkillers or potent narcotics for rapid relief. However, their use may also lead to adverse side effects, including osteoporosis, ocular issues, memory impairment, gastrointestinal complications and damages, increased appetite, and reduced immune resistance to infections, among others. As a result of concerns regarding the challenges and potential harmful side effects associated with these treatments, there is a growing emphasis on the identification and development of alternative methods.

[0004] In recent years, there has been growing interest in the treatments based on natural and herbal substances. Consequently, the market for natural and herbal products, both in the form of herbal medicines available in pharmacies and as bulk raw materials, has been experiencing continuous growth. Additionally, the adoption of advanced non-invasive drug delivery methods, such as nanotechnology, which enables the targeted delivery of drugs and natural substances through the skin, has gained significant interest and acceptance in the field.

[0005] Therefore, a cost effective, safe, and easy-to-use nanofiber-based skin patch comprising a plurality of natural substance has been developed to alleviate pain, swelling as well as inflammation.SUMMARY

[0006] This summary is intended to provide an overview of the subject matter of the present disclosure, and is not intended to identify essential elements or key elements of the subject matter, nor is it intended to be used to determine the scope of the claimed implementations. Its sole purpose is to present some concepts of one or more exemplary aspects in a simplified form as a prelude to the more detailed description that is presented later. The proper scope of the present disclosure may be ascertained from the claims set forth below in view of the detailed description below and the drawings.

[0007] One or more exemplary embodiments describe a nanofiber-based skin patch for alleviating pain, swelling, and inflammation. Exemplary nanofiber-based skin patch may comprise a nanofibrous layer, a skin adhesive layer, a non-woven layer, and a protective layer.

[0008] In an exemplary embodiments, exemplary nanofibrous layer may comprise at least one macromolecule and at least one natural active agent. In one or more exemplary embodiments, the at least one macromolecule comprises polylactic acid (PLA), polyvinyl alcohol (PVA), polycaprolactone (PCL), chitosan, cellulose acetate, collagen, silk, starch, gelatin, pectin, chitin, hyaluronic acid, Aloe Vera, fibrin, or a combination thereof. In one or more exemplaryembodiments, exemplary natural active agent may comprise a mint extract, a rose madder extract, a rosemary extract, a lavender extract, a clove extract, an arnica extract, a ginger extract, a sage extract, a ginseng extract, a garlic extract, curcumin, bromelain, honey, royal jelly, propolis, or a combination thereof.

[0009] In one or more exemplary embodiments, exemplary nanofibrous layer may comprise at least one macromolecule and a plurality of natural active agents. In one or more exemplary embodiments, exemplary plurality of natural active agents may comprise a composition of a mint extract, a rose madder extract, a rosemary extract, a lavender extract, a clove extract, an arnica extract, a ginger extract, a sage extract, a ginseng extract, a garlic extract, curcumin, bromelain, honey, royal jelly, and propolis. In an exemplary embodiment, an exemplary loading amount of exemplary plurality of natural active agents may be in a range of 50 mg to 300 mg.

[0010] In an exemplary embodiment, exemplary nanofibrous layer may be fabricated on an exemplary top surface of exemplary non-woven layer and exemplary non-woven layer may be connected to exemplary skin adhesive layer. Furthermore, in one or more exemplary embodiments, exemplary protective layer may configure to protect exemplary nanofibrous layer.

[0011] This Summary may introduce a number of concepts in a simplified format; the concepts are further disclosed within the “Detailed Description” section. This Summary is not intended to configure essential / key features of the claimed subject matter, nor is intended to limit the scope of the claimed subject matter.BRIEF DESCRIPTION OF THE DRAWINGS

[0012] The novel features which are believed to be characteristic of the present disclosure, as to its structure, organization, use and method of operation, together with further objectives and advantages thereof, will be better understood from the following drawings in which anexemplary embodiment will now be illustrated by way of example. It is expressly understood, however, that the drawings are for the purpose of illustration and description only and are not intended as a definition of the limits of the present disclosure. Exemplary embodiments will now be described by way of example in association with the accompanying drawings in which:

[0013] FIG. 1 illustrates a schematic view of an exemplary nanofiber-based skin patch for alleviating pain, swelling, and inflammation, consistent with one or more exemplary embodiments of the present disclosure;

[0014] FIG. 2 illustrates a flowchart of an exemplary fabrication method for producing an exemplary nanofibrous layer of an exemplary nanofiber-based skin patch, consistent with one or more exemplary embodiments of the present disclosure;

[0015] FIG. 3 illustrates a FTIR spectra of an exemplary nanofibrous layer of an exemplary nanofiber-based skin patch, consistent with one or more exemplary embodiments of the present disclosure;

[0016] FIG. 4 illustrates scanning electron microscope (SEM) images of an exemplary nanofibrous layer of an exemplary nanofiber-based skin patch, consistent with one or more exemplary embodiments of the present disclosure;

[0017] FIG. 5 illustrates a water contact angel of an exemplary nanofibrous layer of an exemplary nanofiber-based skin patch, consistent with one or more exemplary embodiments of the present disclosure;

[0018] FIG. 6 illustrates a release profile of an exemplary plurality of natural active agents from an exemplary nanofibrous layer of an exemplary nanofiber-based skin patch in phosphate buffered saline (PBS), consistent with one or more exemplary embodiments of the present disclosure;

[0019] FIG. 7 illustrates a cell viability result of an exemplary nanofibrous layer of an exemplary nanofiber-based skin patch via MTT assay after 24 hours, consistent with one or more exemplary embodiments of the present disclosure;

[0020] FIG. 8 illustrates a score pain plot of animals without treatment (control group) and treatment with an exemplary nanofibrous layer of an exemplary nano -fiber based skin patch and an exemplary commercial analgesic drug, consistent with one or more exemplary embodiments of the present disclosure;

[0021] FIG. 9 illustrates a paw edema thickness plot of animals without treatment (control group) and treatment with an exemplary nanofibrous layer of an exemplary nano-fiber based skin patch and an exemplary commercial anti-inflammation drug, consistent with one or more exemplary embodiments of the present disclosure; and

[0022] FIG. 10 illustrates a TGF-P gene expression plot of animals without treatment (control group) and treatment with an exemplary nanofibrous layer of an exemplary nano-fiber based skin patch, an exemplary commercial analgesic drug, and an exemplary commercial antiinflammation drug, consistent with one or more exemplary embodiments of the present disclosure.DETAILED DESCRIPTION

[0023] In the following detailed description, numerous specific details are set forth by way of examples to provide a thorough understanding of the relevant teachings related to the exemplary embodiments. However, it should be apparent that the present teachings may be practiced without such details. In other instances, well known methods, procedures, components, and / or circuitry have been described at a relatively high-level, without detail, in order to avoid unnecessarily obscuring aspects of the present teachings.

[0024] The following detailed description is presented to enable a person skilled in the art to make and use the methods and devices disclosed in one or more exemplary embodimentsof the present disclosure. For purposes of explanation, specific nomenclature is set forth to provide a thorough understanding of the present disclosure. However, it will be apparent to one skilled in the art that these specific details are not required to practice the disclosed exemplary embodiments. Descriptions of specific exemplary embodiments are provided only as representative examples. Various modifications to the exemplary implementations will be plain to one skilled in the art, and the general principles defined herein may be applied to other implementations and applications without departing from the scope of the present disclosure. The present disclosure is not intended to be limited to the implementations shown, but is to be accorded the widest possible scope consistent with the principles and features disclosed herein.

[0025] Disclosed herein is an exemplary cost-effective and easy-to-use nanofiber-based skin patch comprising an exemplary nanofibrous layer for alleviating pain, swelling, and inflammation. In an exemplary embodiment, “nanofibrous layer” may refer to a layer comprising a plurality of fibers that have an average diameter less than 1000 nm, particularly less than 500 nm, and more particularly less than 150 nm. In an exemplary embodiment, an exemplary composition of an exemplary plurality of natural active agents may be used to fabricate exemplary nanofibrous layer. In an exemplary embodiment, “natural active agent” may refer to an herbal active ingredient, a natural active ingredient, and / or a combination thereof than can reduce pain, swelling as well as inflammation of a wound after surgery. Using an exemplary plurality of natural active agents can result in fabrication of an exemplary nontoxic, biocompatible, and biodegradable skin patch with immediate effectiveness in relieving pain and reducing inflammation and swelling without any side effects.

[0026] FIG. 1 illustrates an exemplary nanofiber-based skin patch 100 for alleviating pain, swelling, and inflammation, consistent with one or more exemplary embodiments of the present disclosure. In an exemplary embodiment, as illustrated in FIG.l, exemplary nanofiberbased skin patch 100 may comprise at least four main layers. An exemplary first layer maycomprise a skin adhesive layer 102 and an exemplary second layer may comprise a non-woven layer 104. In an exemplary embodiment, an exemplary third layer may comprise an exemplary nanofibrous layer 106 such that exemplary nanofibrous layer 106 may be fabricated on an exemplary first surface of exemplary non-woven layer and an exemplary second surface of exemplary non-woven layer may be connected to exemplary skin adhesive layer 102. Furthermore, in an exemplary embodiment, exemplary nanofiber-based skin patch 100 may comprise an exemplary protective layer 108 as an exemplary fourth layer that may configure to protect exemplary nanofibrous layer 106.

[0027] In an exemplary embodiment, exemplary skin adhesive layer 102 may made of, for example, but is not limited to, an exemplary natural macromolecule with an exemplary adhesive property, an exemplary synthetic macromolecule with an exemplary adhesive property, and / or an exemplary combination thereof. In one or more exemplary embodiments, , exemplary skin adhesive layer 102 may made of, for example, but is not limited to, gum Arabic, gelatin, polyethylene (PE), polypropylene (PP), starch, plant-based gums, silicone, acrylic macromolecule, polyvinyl alcohol, an exemplary combination thereof, or other type of materials with adhesive property that are well-known for those skilled in the art. In one or more exemplary embodiments, exemplary skin adhesive layer 102 may be configured to adhere to an exemplary skin of an exemplary subject. In an exemplary embodiment, “subject” may refer to mammals, more particularly human. In an exemplary embodiment, exemplary skin adhesive layer 102 may be configured to adhere to an exemplary skin of exemplary human subjects with male or female sexuality. In one or more exemplary embodiments, exemplary skin adhesive layer 102 may be further configured to stick exemplary nanofibrous layer 106 to an exemplary wound site during an exemplary period of exemplary skin patch 100 use and prevent exemplary nanofibrous layer 106 from separating.

[0028] In an exemplary embodiment, exemplary non-woven layer 104 may be made of, an exemplary synthetic macromolecule, an exemplary natural fiber, an exemplary combination thereof. In one or more exemplary embodiments, exemplary non-woven layer 104 may be made of, for example, but is not limited to, propylene (PP), an exemplary polyester, polyethylene (PE), polyethylene terephthalate, cotton, silk, wool, an exemplary combination thereof, or other types of natural fibers and / or synthetic macromolecules that are well-known for those skilled in the art.

[0029] In an exemplary embodiment, exemplary nanofibrous layer 106 may comprise at least one exemplary macromolecule and at least one exemplary natural active agent. In one or more exemplary embodiment, exemplary macromolecule may comprise, for example, but is not limited to, polylactic acid (PLA), polyvinyl alcohol (PVA), poly caprolactone (PCL), chitosan, cellulose acetate, collagen, silk, starch, gelatin, pectin, chitin, hyaluronic acid, Aloe Vera, fibrin, an exemplary combination thereof, and / or other type of macromolecules that are well-known for those skilled in the art. In an exemplary embodiment, at least one exemplary natural active agent may comprise, for example, but is not limited to, an exemplary mint extract, an exemplary rose madder extract, an exemplary rosemary extract, an exemplary lavender extract, an exemplary clove extract, an exemplary arnica extract, an exemplary ginger extract, an exemplary sage extract, an exemplary ginseng extract, an exemplary garlic extract, an exemplary chamomile extract, an exemplary calendula extract, an exemplary Boswellia extract, an exemplary capsicum extract, an exemplary nettle extract, an exemplary liquorice extract, curcumin, bromelain, honey, royal jelly, propolis, an exemplary combination thereof, and / or other type of natural active agents that are well-known for those skilled in the art. In an exemplary embodiment, an exemplary loading amount of at least one exemplary natural active agent may be in a range of 50 mg to 300 mg.

[0030] In some exemplary embodiments, exemplary nanofibrous layer 106 may comprise at least one exemplary macromolecule and an exemplary plurality of natural active agents. In this exemplary embodiments, exemplary plurality of natural active agents may comprise a composition of an exemplary mint extract, an exemplary rose madder extract, an exemplary rosemary extract, an exemplary lavender extract, an exemplary clove extract, an exemplary arnica extract, an exemplary ginger extract, an exemplary sage extract, an exemplary ginseng extract, an exemplary garlic extract, curcumin, bromelain, honey, royal jelly, propolis. In an exemplary embodiment, an exemplary loading amount of exemplary composition of exemplary plurality of natural active agents may be in a range of 50 mg to 300 mg. In an exemplary embodiment, at least one exemplary macromolecule may comprise an exemplary mixture of polylactic acid (PLA), polyvinyl alcohol (PVA), polycaprolactone (PCL), chitosan, cellulose acetate, collagen, silk, starch, gelatin, pectin, chitin, hyaluronic acid, Aloe Vera, fibrin, an exemplary combination thereof, and / or other type of macromolecules that are well-known for those skilled in the art.

[0031] In one or more exemplary embodiments, exemplary “mint extract” may refer to an exemplary concentrated form of an exemplary bioactive component that may be extracted from at least one or a mixture of leaves, flowers, and / or stems of an exemplary mint plant utilizing an exemplary extracting method. In one or more exemplary embodiments, “mint plant” may refer to an exemplary flowering plant in mint family that is also known as menthe.

[0032] In one or more exemplary embodiments, exemplary “rose madder extract” may refer to an exemplary an exemplary concentrated form of an exemplary bioactive component that may be extracted from at least one or a mixture of leaves, flowers, and / or root of an exemplary rose madder plant utilizing an exemplary extracting method. In one or more exemplary embodiments, exemplary “rose madder plant” may refer to an herbaceous perennialplant that belongs to Rubiaceae family and also is known as common madder or dyer's madder with the scientific name of Rubia tinctorum.

[0033] In one or more exemplary embodiments, exemplary “rosemary extract” may refer to an exemplary concentrated form of an exemplary bioactive component that may be extracted from the leaves of an exemplary rosemary plant utilizing an exemplary extraction method, for instance, but not limited to, an exemplary solvent extraction, an exemplary steam distillation, or an exemplary combination thereof. In one or exemplary embodiments, “rosemary plant” may refer to an aromatic and evergreen herb native to the Mediterranean region that belongs to the mint family ((Lamiaceae)) with the scientific name of salvia rosmarinus.

[0034] In one or more exemplary embodiments, exemplary “lavender extract” may refer to an exemplary concentrated form of an exemplary bio active component that may be extracted from least one or a mixture of the leaves and flowers of an exemplary rosemary plant utilizing an exemplary extracting method, for instance, but not limited to, an exemplary solvent extraction, an exemplary steam distillation, or an exemplary combination thereof. In one or more exemplary embodiments, “rosemary plant” may refer to an exemplary fragrant, flowering plant native to the Eurasia region that belongs to the mint family (Lamiaceae) with the scientific name of Lavandula and is well-known for its aromatic flowers.

[0035] In one or more exemplary embodiments, exemplary “clove extract” may refer to an exemplary concentrated form of an exemplary bio active component that may be extracted from cloves utilizing an exemplary extracting method, for instance, but not limited to, an exemplary solvent extraction, an exemplary steam distillation, or an exemplary combination thereof. In one or more exemplary embodiments, “cloves” may refer to aromatic flower buds of a tree in the Myrtaceae, family native to the Maluku Islands in Indonesia and with the scientific name of Syzygium aromaticum.

[0036] In one or more exemplary embodiments, exemplary “arnica extract” may refer to an exemplary concentrated form of an exemplary bio active component that may be extracted from flowers of the mountain arnica plant utilizing an exemplary extracting method, for instance, but not limited to, an exemplary solvent extraction, an exemplary steam distillation, or an exemplary combination thereof. In one or more exemplary embodiments, “mountain arnica” may refer to a flowering plant in the daisy family Asteraceae, native to the to Europe and parts of North America with the scientific name of Arnica montana.

[0037] In one or more exemplary embodiments, exemplary “sage extract” may refer to an exemplary concentrated form of an exemplary bio active component that may be extracted from saga plant utilizing an exemplary extracting method, for instance, but not limited to, an exemplary solvent extraction, an exemplary steam distillation, or an exemplary combination thereof. In one or more exemplary embodiments, “saga” may refer to a fragrant, perennial evergreen subshrub native to the Mediterranean region, belonging to the mint family (Lamiaceae), with the scientific name of Salvia officinalis.

[0038] In one or more exemplary embodiments, exemplary “ginseng extract” may refer to an exemplary concentrated form of an exemplary bioactive component that may be extracted from the ginseng plant, typically form roots of the ginseng plant, utilizing an exemplary extracting method. In one or more exemplary embodiments, “ginseng plant” may refer to a perennial herb native to the East Asia and North America, belonging to the Araliaceae family, with the scientific name of Panax.

[0039] In one or more exemplary embodiments, exemplary “ginger extract” may refer to an exemplary concentrated form of an exemplary bioactive component that may be extracted from ginger plant, typically form the roots or rhizomes of the ginger plant, utilizing an exemplary extracting method such as a solvent extraction, and / or a steam distillation. In one or more exemplary embodiments, “ginger plant” may refer to a flowering plant that belongs tothe Zingiberaceae family, native to Southeast Asia, with the scientific name of Zingiber officinale.

[0040] In an exemplary embodiment, exemplary protective layer 108 may be made of an exemplary flexible material. In one or more exemplary embodiments, exemplary protective layer 108 may be made of, for example, but is not limited to, silicon, polyethylene (PE), polypropylene (PP), polyethylene terephthalate (PET), an exemplary combination thereof, or other types of materials that are well-known for those skilled in the art. In an exemplary embodiment, exemplary nano-fibrous layer 106 may be protected from any damage utilizing exemplary protective layer 108 such that exemplary protective layer 108 may be mounted on an exemplary second surface of exemplary nano-fibrous layer. Furthermore, in an exemplary embodiment, exemplary protective layer may be configured to prevent contamination as well as maintain an exemplary integrity of exemplary analgesic active agent contained within exemplary nanofibrous layer 106.

[0041] In one or more exemplary embodiments, an exemplary fabrication method may be used to fabricate exemplary nanofibrous layer 106 of exemplary nanofiber-based skin patch 100. FIG.2 illustrates an exemplary flowchart of an exemplary fabrication method 200 for producing exemplary nanofibrous layer 106, consistent with one or more exemplary embodiments of the present disclosure. In an exemplary embodiment, an exemplary method 200 may comprise: obtaining an exemplary first solution by dissolving at least one exemplary macromolecule to an exemplary solvent (step 202), preparing an exemplary second solution by adding an exemplary composition of an exemplary plurality of analgesic active agents to an exemplary first solution (step 204), and fabricating exemplary nanofibrous layer 106 by electrospinning of an exemplary second solution on exemplary non-woven layer 104 at an exemplary plurality of electrospinning conditions (step 206).

[0042] In further detail with respect to step 202, step 202 may comprise obtaining an exemplary first solution by dissolving at least one macromolecule to an exemplary solvent. In an exemplary embodiment, dissolving at least one macromolecule to an exemplary solvent may comprise adding an exemplary pre-determined amount of at least one exemplary macromolecule to an exemplary pre-determined volume of an exemplary polar solvent, in an exemplary container. In an exemplary embodiment, exemplary container may include, but is not limited to, beakers, tins, flasks, tanks, bottles, buckets, basins, bowls, vials, tubes, barrels, cannisters, etc. In an exemplary embodiment, adding an exemplary pre-determined amount of at least one exemplary macromolecule to an exemplary pre-determined volume of an exemplary polar solvent, in an exemplary container may comprise adding at least one exemplary macromolecule selected from a group of polylactic acid (PLA), polyvinyl alcohol (PVA), polycaprolactone (PCL), chitosan, cellulose acetate, collagen, silk, starch, gelatin, pectin, chitin, hyaluronic acid, Aloe Vera, and fibrin with an exemplary amount in a range of 5 g to 25 g to 100 ml of an exemplary polar solvent, in an exemplary vial, while stirring, e.g., using a magnetic stirrer or an agitation machine (with a speed between about 300 rpm and 400 rpm), for a time duration of about 4 hours to 6 hours at a room temperature. In an exemplary embodiment, exemplary polar solvent may include, for example, but is not limited to, acetic acid, ethanol, ethyl acetate, propanol, butyl alcohol, methanol, an exemplary combination thereof, an exemplary combination thereof with water, and / or other type of polar solvents that are well-known for those skilled in the art.

[0043] In further detail with respect to step 204, step 204 may comprise preparing an exemplary second solution by adding an exemplary composition of an exemplary plurality of analgesic active agents to exemplary first solution. In an exemplary embodiment, adding an exemplary composition of an exemplary plurality of analgesic active agents to exemplary first solution may comprise adding an exemplary pre-determined amount of an exemplarycomposition of exemplary plurality of analgesic active agents to exemplary first solution, in an exemplary container. An exemplary container may comprise, but is not limited to, beakers, tins, flasks, tanks, bottles, buckets, basins, bowls, vials, tubes, barrels, cannisters, etc. In an exemplary embodiment, each of exemplary plurality of analgesic active agents may be used in an exemplary form of, for example, but is not limited to, an exemplary liquid form, an exemplary powder from, an exemplary, encapsulated form, and / or an exemplary combination bthereof. In an exemplary embodiment, adding an exemplary pre-determined amount of an exemplary composition of exemplary plurality of analgesic active agents to exemplary first solution, in an exemplary container may comprise adding an exemplary composition of exemplary plurality of analgesic active agents selected form a group of an exemplary mint extract, an exemplary rose madder extract, an exemplary rosemary extract, an exemplary lavender extract, an exemplary clove extract, an exemplary arnica extract, an exemplary ginger extract, an exemplary sage extract, an exemplary ginseng extract, an exemplary garlic extract, curcumin, bromelain, honey, royal jelly, and propolis with an exemplary concentration in a range of 0.1 %^IN to 5.0 %^IN, more particularly 1.0 %^IN to 3.0 %^IN, to exemplary first solution, in an exemplary vial, while stirring, e.g., using a magnetic stirrer or an agitation machine with an exemplary speed between about 300 rpm and 400 rpm at a room temperature for a time duration of about 2-3 hours.

[0044] In further detail with respect to step 206, step 206 may comprise fabricating exemplary nanofibrous layer 106 by electrospinning of an exemplary second solution on exemplary non-woven layer 104 at an exemplary plurality of electrospinning conditions. In an exemplary embodiment, electrospinning of an exemplary second solution on exemplary nonwoven layer 104 at an exemplary plurality of electrospinning conditions may comprise transferring exemplary second solution to an exemplary injection tool and electrospinning exemplary second solution within exemplary injection tool utilizing an exemplaryelectrospinning machine by adjusting an exemplary plurality of electrospinning parameters. In an exemplary embodiment, an exemplary plurality of electrospinning parameters may include, for example, but is not limited to, an exemplary voltage, an exemplary flow rate, an exemplary tip (of injection tool) to an exemplary collector distance, and an exemplary collector speed. In an exemplary embodiment, electrospinning exemplary second solution within exemplary injection tool utilizing an exemplary electrospinning machine by adjusting an exemplary plurality of electrospinning parameters may comprise electrospinning of exemplary solution of at least one exemplary macromolecule and exemplary plurality of analgesic active agents on an exemplary non-woven layer that may be mounted on an exemplary static collector at an exemplary voltage in a range of 10 kV to 25 kV, an exemplary flow rate in a range of 0.5 ml / h to 1.0 ml / h at an exemplary tip to collector distance in a range of 10 cm to 20 cm.

[0045] In an exemplary embodiment, exemplary nanofibrous layer may have a plurality of fibers with an exemplary average diameter in a range of 100 nm to 150 nm, more particularly in a range of 120 nm to 130 nm.

[0046] In an exemplary embodiment, exemplary nanofiber-based skin patch may be designed to relieve pain, reduce swelling, and mitigate inflammation in different areas of an exemplary subject's body, for example, but not limited to, the nose, face, knees, back, abdomen, and muscles.EXAMPLES

[0047] Hereinafter, one or more exemplary embodiments will be described in further detail with reference to examples. It will be obvious to a person having ordinary skill in the art that these examples may be for illustrative purposes only and are not to be interpreted to limit the scope of the present disclosure.Example 1: Fabrication of Nanofibrous Layer

[0048] In this example, exemplary nanofibrous layer was fabricated based an exemplary process similar to method 200. To fabricate nanofibrous layer, first an exemplary first solution was prepared in a vial. In an exemplary embodiment, exemplary first solution was prepared by dissolving an exemplary mixture of polylactic acid (PLA), polyvinyl alcohol (PVA), polycaprolactone (PCL), chitosan, cellulose acetate, collagen, silk, starch, gelatin, pectin, chitin, hyaluronic acid, Aloe Vera, fibrin in the acetic acid (70%-90%) such that exemplary final concentration of exemplary mixture of polylactic acid (PLA), polyvinyl alcohol (PVA), polycaprolactone (PCL), chitosan, cellulose acetate, collagen, silk, starch, gelatin, pectin, chitin, hyaluronic acid, Aloe Vera, and fibrin was in a range of 5%w / v to 25%w / v, followed by stirring at about 300-400 rpm for about 4-6 hours at a room temperature. Afterward, an exemplary second solution was obtained by adding an exemplary natural active agent. In an exemplary embodiment, to obtain exemplary second solution, an exemplary mixture of a mint extract, a rose madder extract, a rosemary extract, a lavender extract, a clove extract, an arnica extract, a ginger extract, a sage extract, a ginseng extract, a garlic extract, curcumin, bromelain, honey, royal jelly, and propolis was added to exemplary produced exemplary first solution such that an exemplary concentration of exemplary mixture of mint extract, rose madder extract, rosemary extract, lavender extract, clove extract, arnica extract, ginger extract, sage extract, ginseng extract, garlic extract, curcumin, bromelain, honey, royal jelly, and propolis was in a range of 0.1%w / v to 5%w / v, followed by stirring at about 300-400 rpm for about 2-3 hours at a room temperature.

[0049] Then, exemplary nanofibrous layer was fabricated using electrospinning. To fabricate exemplary nanofibrous layer, produced exemplary second solution was fed at 0.5- 1.0 mL / h by a syringe pump into a steel sheet covered by a non-woven layer. A high voltage in a range of 10 kV and 10 cm to 20 cm distance between exemplary tip to exemplary collector were adjusted to fabricate exemplary nanofibrous layer. The obtained exemplary nanofibrouslayer was then dried at a temperature of 40-50 °C for 2-6 hours till a residual acetic acid as a solvent evaporated.Example 2: Characterization of Nanofibrous Layer

[0050] In this example, exemplary produced nanofibrous layer in “Example 1” were characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), contact angle, mechanical test, in vitro cytotoxicity assessment, natural active agents release study, and animal assessment.

[0051] The FTIR spectra of exemplary nanofibrous layer was shown in Fig. 3. As it can be seen in Fig. 3, appearance a broad peak at 3000 cm1to 3600 cm1represent stretching vibration of -NH and -OH bonds in exemplary mixture of polymers as well as mixture of natural active agents, which are involved in hydrogen bonding. Also, a peak at 1708 cm1attributed to stretching vibration of -CH bonds in chitosan. The stretching vibration of -C=O and -COOH were observed at a wavenumber range of 1500 cm1tO 1600 cm1. Furthermore, peaks at 1200 cm-1 to 1400 cm-1 is attributed to amide bonds and peaks at a wavenumber of 900 cm-1 to 1000 cm-1 is related to -CH stretching vibration of aliphatic groups. The observed evidence demonstrates the synergistic interaction of exemplary mixture of natural active agents and exemplary polymeric mixture incorporated into produced exemplary nanofibrous layer, facilitated by the non-covalent and weak bonds, such as hydrogen bonding, formed during obtaining exemplary second solution and mixing of exemplary mixture of natural active agents and polymers.

[0052] Scanning electron microscopy (SEM) images 400 of exemplary produced nanofibrous layer in two different magnifications (1 and 5 pm) are shown in Fig. 4. Exemplary produced nanofibrous layer showed no beads or defect, and displayed a random morphology of exemplary nanofibers. An exemplary mean diameter of 120+35 nm was measured for exemplary nanofibers in produced exemplary nanofibrous layer.

[0053] Hydrophilicity of electrospun scaffolds has an impact on their performance as well as controlling drug delivery. FIG. 5 illustrates exemplary water contact angle 500 of exemplary nanofibrous layer containing exemplary mixture of natural active agents compare to an exemplary nanofibrous layer without exemplary mixture of natural active agents as a blank, consistent with one or more exemplary embodiments of the present disclosure. As illustrated in FIG. 5, an exemplary water contact angle of exemplary nanofibrous layer containing exemplary mixture of natural active agents is about 30 degree, while an exemplary water contact angle of exemplary blank is about 50 degree that indicated exemplary nanofibrous layer containing exemplary mixture of natural active agents have more hydrophilicity due to its composition as well as presence of exemplary natural active agents.

[0054] Release profile 600 of exemplary mixture of natural active agents from exemplary nanofibrous layer in PBS is shown in FIG. 6. Exemplary natural active agents exhibited an initial burst release of approximately 70% from exemplary nanofibrous layer within the first 30 minutes, followed by a prolonged and controlled release over time. This exemplary result indicate that exemplary nanofibrous layer can provide analgesic active agents to a targeted area in the initial hours, effectively preventing pain, swelling, and inflammation in that area. Furthermore, the rapid initial release of exemplary mixture of analgesic active agents from exemplary nanofibrous provides further indication of the presence of weak intermolecular interactions among exemplary constituent materials (polymers and natural active agents).

[0055] The cytotoxicity and cytocompatibility of the fabricated exemplary nanofibrous layer were assessed through the viability of fibroblast cells cultured on its surface using the MTT assay after 24 hours. The evaluation of fibroblast cell (L929) viability 700 demonstrated a survival rate exceeding 76% after 24 hours (FIG.7), indicating that exemplary nanofibrous layer exhibits no cytotoxic effects. This result highlights the biocompatibility of exemplarycomposition (polymers as well as natural active agents) used in fabrication of exemplary nanofibrous layer.

[0056] Furthermore, a skin sensitization test was conducted using a rat model (Wistar male rats) in compliance with ISO 10993 standards, which are required for all skin-related medical products. The exemplary results (as set forth in Table.1) indicated no skin sensitization, as evidenced by a zero response in terms of edema and erythema upon contact with fabricated exemplary nanofibrous layer. Consequently, fabricated exemplary nanofibrous layer demonstrated lack of skin sensitization.Table.l: Skin Sensitization Results for Exemplary Nanofibrous Layer Extract

[0057] Additionally, exemplary results of a skin irritation test using Wistar male rat model in compliance with the ISO 10993 standard indicated no skin irritation, as demonstrated by a zero response (Table.2) in terms of edema and erythema upon contact with fabricated exemplary nanofibrous layer. These exemplary results confirms exemplary nanofibrous layer has a non-irritating nature.Table.2: Skin Irritation Results for Exemplary Nanofibrous Layer

[0058] In addition, exemplary results of an acute systemic toxicity test conducted on aWistar male rat model in accordance with the ISO 10993 standard, demonstrated the absence of acute systemic toxicity of exemplary nanofibrous layer, as exemplary clinical evaluations of the skin's response to exemplary extract of fabricated exemplary nanofibrous layer showed no adverse reactions (Table.3).Table.3 Acute Systemic Toxicity Results for Exemplary Nanofibrous Layer Extract

[0059] Exemplary results set forth in Table. 4 indicated the absence of genotoxic effects of exemplary nano fibrous layer extract based on a genotoxicity assessment, utilizing the Comet assay (alkaline comet assay) on a Wistar male rat model in accordance with the ISO 10993 standard. These exemplary results confirmed fabricated exemplary nanofibrous layer does not induce toxicity or damage at the genomic (DNA) level.Table.4: Genotoxicity Results for Exemplary Nanofibrous Layer Extract

[0060] Also, to demonstrate the efficacy and functionality of fabricated exemplary nanofibrous layer containing exemplary mixture of natural active agents for pain reduction, an exemplary pain assessment test was performed using a Wistar male rat model. Exemplary pain assessment test subjects included animals administered with formalin, to evaluate exemplary nanofibrous layer performance under induced pain conditions compared to a control group (group without treatment with analgesic drugs) as well as an exemplary commercial analgesic drugs (opioids). FIG. 8 shows a score pain plot 800 of animals without treatment (control group) and treatment with exemplary nanofibrous layer and opioids, consistent with one or more exemplary embodiments of the present disclosure. As illustrated in FIG. 8, exemplary nanofibrous layer exhibited a substantial reduction in pain within 1 hour of application on exemplary animal model, significantly outperforming the control group. These exemplary results were comparable to those achieved with exemplary commercially analgesic drugs (opioids). Furthermore, exemplary nanofibrous layer demonstrated superior analgesic efficacy during the initial phase of the application, reducing pain twice times more than exemplary commercial counterpart, thereby confirming its enhanced analgesic capabilities.

[0061] In Addition, to demonstrate the efficacy and performance of exemplary nanofibrous layer containing exemplary mixture of natural active agents for reducing edema (swelling) and inflammation, an exemplary edema reduction test and anti-inflammatory test, respectively, were conducted on a Wistar male rat model. Both exemplary edema and inflammation reduction tests subject paw of included animals administered with exemplary inflammation and swelling-inducing agents, for example, carrageenan.

[0062] Exemplary edema reduction test evaluates exemplary nanofibrous layer performance under induced swelling conditions compared to a control group (group without treatment with anti-inflammation drugs) as well as an exemplary commercial drugs, for example indomethacin. FIG. 9 illustrates a paw edema thickness plot 900 of animals withouttreatment (control group) and treated with exemplary nanofibrous layer and indomethacin, consistent with one or more exemplary embodiments of the present disclosure. As can be seen in FIG. 9, exemplary nanofibrous layer statistically reduced skin edema (swelling) induced by carrageenan injection compared to exemplary control group. Although the swelling reduction achieved by exemplary nanofibrous layer appeared to outperform exemplary commercial indomethacin and the difference was not significant. Nonetheless, it can be concluded that exemplary nanofibrous layer performed comparably to exemplary commercially available drug, demonstrating slightly enhanced efficacy.

[0063] TGF-P is an inflammatory mediator and regulatory protein, the expression of which is elevated during the inflammatory process. As a pro-inflammatory factor, a reduction in TGF-P levels may indicate a reduction in inflammation within the body. FIG. 10 illustrates a TGF-P gene expression plot 1000 of animals without treatment (control group) and treated with exemplary nanofibrous layer, opioids as an exemplary commercial analgesic drug, and indomethacin as an exemplary commercial anti-inflammation drug, consistent with one or more exemplary embodiments of the present disclosure. As can be seen in FIG.10, the control group showed an increment of the TGF-P expression due to the carrageenan injection, leading to inflammation. Also, the animals that received only the opioid drug as treatment, the expression of this protein was elevated and similar to the control group. These exemplary results suggest that exemplary opioid drug is ineffective in reducing inflammation, while it’s effective for pain relief. In contrast, the animals treated with exemplary nanofibrous layer as well as exemplary commercial anti-inflammatory drug (indomethacin) exhibited a significant reduction in the expression of inflammation factor. Therefore, produced nanofibrous layer containing exemplary mixture of natural active agents effectively reduced exemplary inflammatory marker, demonstrating its anti-inflammatory properties and indicating its potential to compete with exemplary commercial product.

[0064] While the foregoing has described what are considered to be the best mode and / or other examples, it is understood that various modifications may be made therein and that the subject matter disclosed herein may be implemented in various forms and examples, and that the teachings may be applied in numerous applications, only some of which have been described herein. It is intended by the following claims to claim any and all applications, modifications and variations that fall within the true scope of the present teachings.

[0065] Unless otherwise stated, all measurements, values, ratings, positions, magnitudes, sizes, and other specifications that are set forth in this specification, including in the claims that follow, are approximate, not exact. They are intended to have a reasonable range that is consistent with the functions to which they relate and with what is customary in the art to which they pertain.

[0066] The scope of protection is limited solely by the claims that now follow. That scope is intended and should be interpreted to be as broad as is consistent with the ordinary meaning of the language that is used in the claims when interpreted in light of this specification and the prosecution history that follows and to encompass all structural and functional equivalents. Notwithstanding, none of the claims are intended to embrace subject matter that fails to satisfy the requirement of Sections 101, 102, or 103 of the Patent Act, nor should they be interpreted in such a way. Any unintended embracement of such subject matter is hereby disclaimed.

[0067] Except as stated immediately above, nothing that has been stated or illustrated is intended or should be interpreted to cause a dedication of any component, step, feature, object, benefit, advantage, or equivalent to the public, regardless of whether it is or is not recited in the claims.

[0068] It will be understood that the terms and expressions used herein have the ordinary meaning as is accorded to such terms and expressions with respect to their corresponding respective areas of inquiry and study except where specific meanings have otherwise been setforth herein. Relational terms such as first and second and the like may be used solely to distinguish one entity or action from another without necessarily requiring or implying any actual such relationship or order between such entities or actions. An element proceeded by “a” or “an” does not, without further constraints, preclude the existence of additional identical elements in the process, method, article, or apparatus that comprises the element.

[0069] Unless otherwise stated, all measurements, values, ratings, positions, magnitudes, sizes, and other specifications that are set forth in this specification, are approximate, not exact. They are intended to have a reasonable range that is consistent with the functions to which they relate and with what is customary in the art to which they pertain.

[0070] It will be understood that the terms and expressions used herein have the ordinary meaning as is accorded to such terms and expressions with respect to their corresponding respective areas of inquiry and study, except where specific meanings have otherwise been set forth herein. Relational terms such as “first” and “second” and the like may be used solely to distinguish one entity or action from another without necessarily requiring or implying any actual such relationship or order between such entities or actions.

[0071] The Abstract of the Disclosure is provided to allow the reader to quickly ascertain the nature of the technical disclosure. It is submitted with the understanding that it will not be used to interpret or limit the scope or meaning of the claims. In addition, in the foregoing Detailed Description, it may be seen that various features are grouped together in various implementations. This is for purposes of streamlining the disclosure, and is not to be interpreted as reflecting an intention that the claimed implementations require more features than are expressly recited in each claim. Rather, as the following claims reflect, inventive subject matter lies in less than all features of a single disclosed implementation. Thus, the following claims are hereby incorporated into the Detailed Description, with each claim standing on its own as a separately claimed subject matter.

[0072] While various implementations have been described, the description is intended to be exemplary, rather than limiting and it will be apparent to those of ordinary skill in the art that many more implementations and implementations are possible that are within the scope of the implementations. Although many possible combinations of features are shown in the accompanying figures and discussed in this detailed description, many other combinations of the disclosed features are possible. Any feature of any implementation may be used in combination with or substituted for any other feature or element in any other implementation unless specifically restricted. Therefore, it will be understood that any of the features shown and / or discussed in the present disclosure may be implemented together in any suitable combination. Accordingly, the implementations are not to be restricted except in light of the attached claims and their equivalents. Also, various modifications and changes may be made within the scope of the attached claims.

Claims

What is claimed is:

1. A nanofiber-based skin patch for alleviating pain, swelling, and inflammation comprising a nanofibrous layer comprising at least one macromolecule and at least one natural active agent.

2. The nanofiber-based skin patch of claim 1, wherein the at least one macromolecule comprises polylactic acid (PLA), polyvinyl alcohol (PVA), polycaprolactone (PCL), chitosan, cellulose acetate, collagen, silk, starch, gelatin, pectin, chitin, hyaluronic acid, Aloe Vera, fibrin, or a combination thereof.

3. The nanofiber-based skin patch of claim 1, wherein the at least one natural active agent comprises a mint extract, a rose madder extract, a rosemary extract, a lavender extract, a clove extract, an arnica extract, a ginger extract, a sage extract, a ginseng extract, a garlic extract, curcumin, bromelain, honey, royal jelly, propolis, or a combination thereof.

4. The nanofiber-based skin patch of claim 1, wherein a loading amount of at least one natural active agent is in a range of 50 mg to 300 mg.

5. The nanofiber-based skin patch of claim 1, further comprising: a skin adhesive layer; a non-woven layer, wherein the nanofibrous scaffold may be fabricated on the nonwoven layer and the non-woven layer is connected to the skin adhesive layer; and a protective layer configure to protect the nanofibrous scaffold.

6. A nanofiber-based skin patch for alleviating pain, swelling, and inflammation comprising: a skin adhesive layer; a nanofibrous layer comprising at least one macromolecule and a composition of natural active agents comprising a mint extract, a rose madder extract, a rosemary extract, alavender extract, a clove extract, an arnica extract, a ginger extract, a sage extract, a ginseng extract, a garlic extract, curcumin, bromelain, honey, royal jelly, propolis; a non-woven layer configure to connect the nanofibrous layer to the skin adhesive layer, wherein the nanofibrous scaffold is fabricated on a top surface of non-woven layer; and a protective layer configure to protect the nanofibrous layer.

7. The nanofiber-based skin patch of claim 6, wherein the at least one macromolecule comprises polylactic acid (PLA), polyvinyl alcohol (PVA), polycaprolactone (PCL), chitosan, cellulose acetate, collagen, silk, starch, gelatin, pectin, chitin, hyaluronic acid, Aloe Vera, fibrin, or a combination thereof.

8. The nanofiber-based skin patch of claim 6, wherein a loading amount of the composition of natural active agents is in a range of 50 mg to 300 mg.

9. A fabrication method for producing a nanofibrous layer of a nanofiber-based skin patch, the fabrication method comprising: obtaining a first solution by dissolving at least one macromolecule to at least one solvent; preparing a second solution by adding a composition of a plurality of analgesic active agents selected from a group of a mint extract, a rose madder extract, a rosemary extract, a lavender extract, a clove extract, an arnica extract, a ginger extract, a sage extract, a ginseng extract, a garlic extract, curcumin, bromelain, honey, royal jelly, propolis; and fabricating the nanofibrous layer by electrospinning of the second solution on a nonwoven layer at a voltage in a range of 10 kV to 25 kV and a flow rate in a range of 0.5 ml / h to 1.0 ml / h.

10. The fabrication method of claim 9, wherein at least one macromolecule comprises polylactic acid (PLA), polyvinyl alcohol (PVA), polycaprolactone (PCL), chitosan, cellulose acetate,collagen, silk, starch, gelatin, pectin, chitin, hyaluronic acid, Aloe Vera, fibrin, or a combination thereof.

11. The Fabrication method of claim 9, wherein the at least one solvent is a polar solvent.The fabrication method of claim 9, wherein the at least one solvent comprises acetic acid, ethanol, ethyl acetate, propanol, butyl alcohol, methanol, a combination thereof, or a combination thereof with water.

12. The fabrication method of claim 9, wherein a concentration of the at least one macromolecule in the first solution is in range of 5%w / v to 25%w / v.

13. The fabrication method of claim 9, wherein a concentration of the at least one analgesic active agent in the second solution is in range of 0.1%w / v to 5.0%w / v.

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