A shape memory nasal cavity support, its preparation method and usage method

Abstract

This invention provides a shape memory nasal stent, its preparation method, and its usage method, belonging to the field of medical device technology. The stent includes a nasal stent body and a hydrogel layer, with the hydrogel layer covering the outer side of the nasal stent body. The nasal stent body has a mesh-like three-dimensional structure and is made of shape memory polymer. The shape memory nasal stent includes a temporary shape and an initial shape. Both the initial and temporary shapes are cylindrical, with the diameter of the initial shape being larger than that of the temporary shape. When the shape memory nasal stent is stimulated by external factors, it transforms from the temporary shape to the initial shape. The shape memory nasal stent provided by this invention, after implantation into the nasal cavity, provides excellent fit to the nasal mucosa, offering greater softness and comfort. Furthermore, the transformation between the temporary and initial shapes before and after implantation avoids damage to the nasal cavity.

Description

Technical Field

[0001] This invention relates to the field of medical device technology, and more specifically, to a shape memory nasal cavity stent and its preparation and usage methods. Background Technology

[0002] Swelling of the nasal mucosa, also known as nasal mucosal enlargement, is commonly seen in rhinitis and is caused by inflammation of the nasal mucosa leading to swelling. Nasal mucosal swelling or edema is one of the main causes of nasal congestion. If nasal mucosal swelling is not effectively treated, it can seriously affect people's normal lives, mainly manifesting as dizziness, fatigue, low-grade fever, excessive nasal discharge, blood-tinged nasal discharge, and sleep apnea.

[0003] To alleviate the symptoms of nasal mucosal swelling, a nasal stent can be implanted in the nasal cavity. However, the existing nasal stents have a relatively simple shape and are usually not flexible enough to fit the nasal mucosa well. Furthermore, the implantation and removal of the nasal stent can easily cause friction in the nasal cavity, thus damaging it. Summary of the Invention

[0004] The problem addressed by this invention is how to provide a shape-memory nasal support that can fit well to the nasal mucosa while avoiding damage to the nasal cavity.

[0005] To address the aforementioned issues, this invention provides a shape memory nasal support, comprising a nasal support body and a hydrogel layer, wherein the hydrogel layer covers the outer side of the nasal support body, and wherein the nasal support body has a mesh-like three-dimensional structure and is made of a shape memory polymer.

[0006] The shape memory nasal support includes a temporary shape and an initial shape. Both the initial shape and the temporary shape of the shape memory nasal support are cylindrical. The initial shape of the shape memory nasal support matches the size of the nasal cavity, and the diameter of the initial shape of the shape memory nasal support is larger than the diameter of the temporary shape of the shape memory nasal support. When the shape memory nasal support is stimulated by external factors, it is used to transform from the temporary shape to the initial shape.

[0007] Preferably, the frame grid unit of the mesh three-dimensional structure is a rhombus or a rhombus variant with curved four sides.

[0008] Preferably, the shape memory polymer includes one or more of the following: polylactic acid-based, polycaprolactone-based, polyethylene glycol-based, alginate-based, polydopamine-based, gelatin-based, polydopamine-based, polyvinyl alcohol-based, hydroxymethyl cellulose-based, polyacrylamide-based, and polyacrylate-based shape memory polymers.

[0009] Preferably, the shape memory nasal stent further includes a drug loaded on the nasal stent body or the hydrogel layer, the drug including one or more of aspirin, metamizole, acetaminophen, indomethacin, piroxicam, ketorolac, cortisone, hydrocortisone, dexamethasone, or aminoglycoside broad-spectrum antibiotics.

[0010] Preferably, the inner wall surface of the nasal cavity support body has a biomimetic micro-nano structure based on gecko skin, damselfly wings, dragonfly wings, cicada wings, or lotus leaves.

[0011] Preferably, the shape memory nasal cavity support further includes bee venom, turmeric extract, and zinc dioxide powder, wherein the turmeric extract and the zinc dioxide powder are uniformly distributed on the nasal cavity support body, and the bee venom is distributed at the tip of the biomimetic micro / nano structure.

[0012] This invention comprises a nasal cavity support body made of shape memory polymer and a hydrogel layer, forming a shape memory nasal cavity support. The nasal cavity support body possesses shape memory properties, enabling it to transform between a temporary and an initial shape under external stimuli (temperature, magnetic field, or light). The nasal cavity support body made of shape memory polymer exhibits excellent mechanical properties, providing good support when implanted in the nasal cavity, allowing it to adhere to the nasal mucosa. The hydrogel layer covering the outer surface is relatively soft and reduces stress when adhering to the nasal mucosa. The shape memory nasal stent alleviates the feeling of a foreign body in the nasal cavity. Furthermore, when in its temporary shape, it is small in size, facilitating implantation. Due to its shape memory properties, applying external stimulation to the stent after implantation allows it to revert to its initial shape. Because of its mesh-like three-dimensional structure, the stent conforms well to the nasal mucosa, providing excellent support and resisting swelling and deformation of the nasal mucosa under complex mechanical conditions, thus preventing serious complications such as breathing difficulties or even apnea caused by nasal mucosal swelling. The shape memory nasal stent provided by this invention provides excellent conformation to the nasal mucosa after implantation, and avoids damage to the nasal cavity by transitioning between its temporary and initial shapes before and after implantation.

[0013] In addition, the present invention also provides a method for preparing a shape memory nasal cavity support, which is used to prepare the shape memory nasal cavity support as described above, including the following steps:

[0014] Step S1: Construct a three-dimensional structural model of the initial shape of the shape memory nasal cavity support;

[0015] Step S2: Prepare shape memory polymer, and print the shape memory polymer according to the three-dimensional structural model using 4D printing method to obtain the nasal cavity support body with the initial shape;

[0016] Step S3: Prepare hydrogel, coat the hydrogel onto the outside of the nasal cavity support body of the initial shape, and form a hydrogel layer on the outside of the nasal cavity support body to obtain the shape memory nasal cavity support of the initial shape.

[0017] Step S4: Heat the initial shape of the shape memory nasal cavity support to above the glass transition temperature, apply external force, and then cool it to below room temperature to obtain a temporary shape of the shape memory nasal cavity support.

[0018] Preferably, one or more of the following are added during the preparation of the shape memory polymer and the hydrogel: iron oxide, iron oxide, gold nanoparticles, silver nanoparticles, polypyrrole, graphene, or graphene oxide.

[0019] Preferably, step S3 includes:

[0020] Step S31: Dissolve 300 parts of N-isopropylacrylamide in 500 parts of water to form an N-isopropylacrylamide solution, remove air bubbles under vacuum, dissolve 100 parts of linear methylcellulose in 800 parts of water to form a linear methylcellulose solution, remove air bubbles under vacuum, mix the N-isopropylacrylamide solution and the linear methylcellulose solution evenly, add 0.167 parts of N,N'-methylenebisacrylamide, put it in a container and seal it, and shake it in an ultrasonic cleaner for 6 hours to remove air bubbles, to obtain a mixed solution;

[0021] Step S32: The mixed solution is coated on the outer side of the nasal cavity support body of the initial shape to form a coating with a thickness of about 0.5 mm. The coating is polymerized for 5 h under nitrogen atmosphere at 10°C and ultraviolet light at 360 nm-370 nm to form a hydrogel layer, thereby obtaining the shape memory nasal cavity support of the initial shape.

[0022] The method for preparing the shape memory nasal cavity support provided by this invention has the same beneficial effects as the prior art, and will not be repeated here.

[0023] The present invention also provides a method for using a shape memory nasal cavity support, which, based on the above-mentioned shape memory nasal cavity support, includes:

[0024] Step T1: Before implantation into the nasal cavity, apply temperature, electromagnetic or light stimulation to the initial shape memory nasal cavity support, and use external force to transform the initial shape shape memory nasal cavity support into a temporary shape shape memory nasal cavity support.

[0025] Step T2: The temporary shape memory nasal support is implanted into the user's nasal cavity. Stimulation is applied to the temporary shape memory nasal support to restore it to the initial shape until it fits the user's nasal mucosa.

[0026] Step T3: When it is necessary to remove the shape memory nasal support from the nasal cavity, apply the same stimulation to the shape memory nasal support again, and use external force to transform the shape memory nasal support into the temporary shape, and then remove it.

[0027] The method of using the shape memory nasal stent provided by this invention involves deforming the shape memory nasal stent into a smaller temporary shape before implantation to avoid damage to the nasal mucosa during the implantation process. After implantation, the shape memory nasal stent can be transformed back to its initial shape by applying stimulation until it adheres to the nasal mucosa, providing good support for the nasal mucosa and resisting complications such as breathing difficulties and sleep apnea caused by swelling and deformation of the nasal mucosa. Because it uses shape memory material, the shape memory nasal stent can gradually degrade within the nasal cavity. If it needs to be removed midway, the shape memory nasal stent can be restored to its temporary shape by stimulating it again and applying external force, avoiding secondary harm during the removal process. Attached Figure Description

[0028] Figure 1 This is a schematic diagram of the shape memory nasal cavity support structure with the initial shape in an embodiment of the present invention;

[0029] Figure 2 This is a schematic diagram of the structure of the shape memory nasal cavity support with a temporary shape in an embodiment of the present invention;

[0030] Figure 3 This is a schematic diagram of the shape memory nasal cavity support structure after implantation in an embodiment of the present invention;

[0031] Figure 4 This is a schematic diagram of the frame grid unit of the shape memory nasal cavity support in an embodiment of the present invention;

[0032] Figure 5 This is a schematic flowchart of the method for preparing the shape memory nasal cavity support in an embodiment of the present invention;

[0033] Figure 6 This is a flowchart illustrating the method of using the shape memory nasal cavity support in an embodiment of the present invention. Detailed Implementation

[0034] To make the above-mentioned objects, features and advantages of the present invention more apparent and understandable, specific embodiments of the present invention will be described in detail below.

[0035] It should be noted that, unless otherwise specified, the features in the embodiments of this invention can be combined with each other. The terms "comprising," "including," "containing," and "having" are non-limiting, meaning that other steps and other components that do not affect the results can be added. The above terms cover the terms "composed of" and "substantially composed of." Unless otherwise specified, the materials, equipment, and reagents are commercially available.

[0036] This invention provides a shape memory nasal support, comprising a nasal support body and a hydrogel layer, wherein the hydrogel layer covers the outer side of the nasal support body, and the nasal support body has a mesh-like three-dimensional structure and is made of a shape memory polymer.

[0037] The shape memory nasal support includes a temporary shape and an initial shape. Both the initial shape and the temporary shape of the shape memory nasal support are cylindrical. The initial shape of the shape memory nasal support matches the size of the nasal cavity, and the diameter of the initial shape of the shape memory nasal support is larger than the diameter of the temporary shape of the shape memory nasal support. When the shape memory nasal support is stimulated by external factors, it is used to transform from the temporary shape to the initial shape.

[0038] The nasal scaffold body made of shape memory polymer has good mechanical properties and can switch between temporary and initial shapes under stimulation; the hydrogel layer is composed of hydrogel, which is a three-dimensional biomaterial with high water content and high permeability. It can carry stem cells and drugs and has a sustained-release drug function. Its tissue adhesion properties can simulate the biological and chemical properties of human soft tissue, and provide better tissue adhesion and softness when in contact with the nasal mucosa.

[0039] In one embodiment, the hydrogel layer is made of shape memory hydrogel, which is an excellent biomaterial that can temporarily fix and restore its shape under external stimuli, and work better with the nasal cavity support body.

[0040] This embodiment utilizes a nasal cavity scaffold composed of a hydrogel layer made of shape memory polymer. The nasal cavity scaffold possesses shape memory properties, enabling it to transform between a temporary and initial shape under external stimuli. The shape memory polymer-made nasal cavity scaffold body exhibits excellent mechanical properties, providing good support when implanted into the nasal cavity, allowing it to conform to the nasal mucosa. The outer hydrogel layer is relatively soft, reducing the foreign body sensation in the nasal cavity when in contact with the nasal mucosa. Furthermore, when the shape memory nasal stent is in its temporary shape, its small size facilitates implantation into the nasal cavity. Due to its shape memory properties, applying external stimulation to the implanted stent allows it to revert to its initial shape. Because the shape memory nasal stent has a mesh-like three-dimensional structure, it can conform to the nasal mucosa under the influence of nasal resistance, providing excellent support. It resists swelling and deformation of the nasal mucosa under complex mechanical conditions, avoiding serious complications such as breathing difficulties or even apnea caused by nasal mucosal swelling. The shape memory nasal stent provided in this embodiment can achieve good conformation to the nasal mucosa after implantation, and avoids damage to the nasal cavity by transitioning between its temporary and initial shapes before and after implantation.

[0041] For example, external stimuli such as temperature, light, or magnetic field can be applied to the shape memory nasal stent to cause it to deform.

[0042] Figures 1-3 These are the initial shape, temporary shape, and shape after implantation into the nasal cavity of the shape memory nasal stent provided in this embodiment of the invention. Before implantation, the shape memory nasal stent has an initial shape, as shown in the following structure. Figure 1 As shown, the initial shape memory nasal implant's dimensions match the user's nasal cavity dimensions, especially the diameter and length, ensuring a good fit after implantation. To prevent friction between the implant and the nasal cavity during implantation, the initial shape memory nasal implant is stimulated and subjected to external force, then rapidly cooled to below room temperature to form a temporary shape memory nasal implant, as shown in the diagram. Figure 2 As shown, the temporary shape memory nasal stent has a small diameter, avoiding damage caused by friction with the nasal cavity during implantation. After implantation, stimulation can restore the temporary shape memory nasal stent to its initial shape. During the restoration process, constrained by the nasal cavity, the shape memory nasal stent fully adheres to the nasal mucosa and does not deform further. The structure is as follows. Figure 3As shown, the shape memory nasal cavity support fits well with the nasal mucosa at this time, and can resist the swelling and deformation of the nasal mucosa under complex mechanical service environment, avoiding serious complications such as difficulty breathing or even sleep apnea caused by swelling of the nasal mucosa.

[0043] In one embodiment, the stiffness of the nasal stent body can be adjusted to provide appropriate support and pressure at different stages of treatment after the shape memory nasal stent is implanted into the nasal cavity. This can be achieved by adding support rods of different densities and shapes to the mesh-like three-dimensional structure of the nasal stent body.

[0044] In one embodiment, the frame mesh unit of the mesh three-dimensional structure is a rhombus or a rhombus variant with curved quadrilaterals. By designing the frame mesh unit of the nasal stent body as a rhombus or a rhombus variant with curved quadrilaterals, the shape memory nasal stent can easily transform between its initial and temporary shapes. After implantation into the nasal cavity, the deformed shape memory nasal stent can form a shape that conforms to the nasal mucosa and can withstand the radial load caused by swelling of the nasal mucosa.

[0045] Furthermore, the structure of the frame mesh unit of the mesh three-dimensional structure is as follows: Figure 4 As shown, the coordinates of the points through which the central spline curve of the frame mesh unit passes are (2, 2), (2.5, 3), (3, 2.5), (3.5, 2) and (4, 3), and four splines are arrayed around the central point (3.5, 1.5) at a 90° angle.

[0046] Furthermore, the frame mesh unit of the mesh three-dimensional structure can also be a rhomboid variant: the four corners of this rhomboid variant are the center point (3.5, 1.5) and array points (2.5, 2), (4.5, 2) and (3.5, 3) of the frame mesh unit, respectively. The diagonal length of this rhomboid variant is 2.24 mm, which is smaller than the length of the spline curve of the center of the frame mesh unit (3.35 mm). Therefore, this variant can increase the detail of the mesh structure and improve the stability and biocompatibility of the scaffold.

[0047] It can also be a four-sided curved rhomboid variant: this variant is a further deformation of the original rhomboid variant, with all four corners curved, the curves passing through the center point and array points of the rhomboid variant. This variant can further increase the surface area and detail of the stent, improving the contact area and stability between the stent and the nasal mucosa. Simultaneously, the four-sided curved shape of this variant allows the stent to better conform to the curved shape of the nasal cavity, reducing pressure on the nasal cavity and alleviating patient discomfort.

[0048] In other words, by designing frame grid unit structures of different shapes and sizes, the embodiments of the present invention can further optimize the performance of the stent and improve its stability, biocompatibility and comfort.

[0049] Shape memory polymers are intelligent polymer materials that can sense environmental changes and have a shape memory effect. By placing a shape memory polymer with a certain initial shape in a special environment (such as external stimuli such as high temperature, magnetic field, electric field, light, etc.), it can be programmed into different temporary shapes such as shape, volume and strain. When the shape memory polymer in the temporary shape is placed in the same environmental conditions as the programming process again, it will slowly recover the initial shape.

[0050] Shape memory polymers used to prepare the nasal cavity support body include one or more of the following: polylactic acid-based, polycaprolactone-based, polyethylene glycol-based, alginate-based, polydopamine-based, gelatin-based, polydopamine-based, polyvinyl alcohol-based, hydroxymethyl cellulose-based, polyacrylamide-based, and polyacrylate-based shape memory polymers.

[0051] Polyacrylate-based shape memory polymers are special polymers possessing shape memory properties. These properties can be modulated by adjusting their chemical structure; that is, they can transform from an initial shape to a predetermined shape in response to external stimuli (such as heat, light, or electricity), and then return to the initial shape upon further stimulation. The shape memory properties of polyacrylate-based shape memory polymers can be regulated by adjusting the types, proportions, and molecular weights of their monomers. These polymers can be used to control drug release, embedding drugs within the polymer and controlling the release rate and time through shape memory regulation, thereby enhancing therapeutic efficacy.

[0052] Wound dressings are a crucial tool in the healing process of chronic wounds caused by slow-healing tissue damage. Active dressings are the latest type of modern wound dressings produced based on biomaterials, inherently biocompatible, biodegradable, and non-toxic. Active dressings are typically incorporating biological substances (such as growth factors and drugs) as well as antibacterial agents to combat infection and promote wound healing, especially for chronic wounds caused by rhinitis.

[0053] In one embodiment, the shape memory nasal stent further includes a drug loaded on the nasal stent body or the hydrogel layer. The drug includes one or more of aspirin, metamizole, acetaminophen, indomethacin, piroxicam, ketorolac, cortisone, hydrocortisone, dexamethasone, broad-spectrum aminoglycoside antibiotics, tumor necrosis factor inhibitors, growth factors, and immunomodulators. The drug is added at a mass ratio of 0-15% of the nasal stent body.

[0054] Among them, aspirin is an antipyretic, analgesic, and anti-inflammatory drug that can inhibit platelet aggregation and prevent thrombosis; aminopyrine has antipyretic, analgesic, and antirheumatic effects; acetaminophen can reduce the synthesis and release of prostaglandins PGE1, bradykinin, and histamine by inhibiting prostaglandin synthase in the hypothalamic thermoregulatory center, making it suitable for patients who are allergic or intolerant to aspirin; piroxicam works by inhibiting cyclooxygenase, reducing the synthesis of prostaglandins in local tissues, and inhibiting leukocyte chemotaxis and the release of lysosomal enzymes; ketorolac is a prostaglandin synthase inhibitor with analgesic, anti-inflammatory, antipyretic, and platelet aggregation-inhibiting effects, with few toxic side effects and no addictive properties; cortisone has anti-inflammatory, anti-allergic, and anti-granulation effects; hydrocortisone has 1.25 times the anti-inflammatory effect of cortisone. It has inhibitory effects on both infectious and non-infectious inflammation. It can increase vascular tone, reduce congestion, and decrease capillary permeability, thereby reducing exudation and edema. It can also relieve symptoms such as redness, swelling, heat, and pain by inhibiting the aggregation of inflammatory cells at the site of inflammation, inhibiting the function of phagocytes, stabilizing lysosomal membranes, and preventing complement from participating in the inflammatory response and the synthesis and release of inflammatory chemical mediators. Aminoglycoside broad-spectrum antibiotics work by binding to bacterial ribosomes and interfering with bacterial protein synthesis. They are a class of bactericidal agents that operate in the stationary phase and are mainly used for infections caused by susceptible aerobic Gram-negative bacilli. In particular, they have a long-lasting post-antibacterial effect against common Gram-negative bacilli such as Pseudomonas aeruginosa, Klebsiella spp., and Escherichia coli. Therefore, they can be used to treat severe nasal tract infections caused by aerobic Gram-negative bacilli. By adding tumor necrosis factor inhibitors, growth factors, or immunomodulators, shape memory nasal stents can exert a wider range of effects. Among them, the addition of tumor necrosis factor inhibitors can reduce inflammatory response and tissue damage, promote wound healing, and make nasal stents more suitable for the treatment of inflammatory diseases; the addition of growth factors can promote tissue regeneration and repair, and accelerate the wound healing process; the addition of immunomodulators can regulate immune response, prevent adverse reactions such as rejection and immunosuppression, thereby improving treatment efficacy and safety.

[0055] Furthermore, tumor necrosis factor inhibitors include one or more of TNF-α inhibitors, IL-1β inhibitors, and IL-6 inhibitors; growth factors include one or more of VEGF, FGF, and TGF-β; and immunomodulators include one or more of IL-2, IL-10, and PD-L1.

[0056] The drug can be added as a raw material to the nasal cavity stent body and / or hydrogel layer preparation material, or it can be placed on the surface of the nasal cavity stent body and / or hydrogel layer by coating or other methods.

[0057] When a nasal stent is implanted in the nasal cavity, bacteria can easily adhere to the surface of the stent when breathing air. Simply using the drug-loaded stent to inhibit bacteria can easily lead to the development of drug resistance during the reproduction process, increasing the difficulty of subsequent antibacterial treatment.

[0058] Inspired by the antibacterial models of nanostructured biological surfaces, such as insect wings and gecko skin, nanostructures with a specific aspect ratio have been shown to effectively inhibit bacterial growth on modified surfaces. This is based on a physical micro / nanostructure-based antibacterial mechanism. In other words, without the addition of chemical bactericides, the bacterial cell walls attached to the nanopillars within the micro / nanostructure are subjected to physical tearing forces exceeding their tolerance, leading to bacterial cell rupture and death. Compared to traditional chemical bactericides, antibacterial surfaces relying entirely on physical structures are safer, more stable, and longer-lasting because they do not depend on any harmful biochemical reagents. Furthermore, by tearing bacteria apart solely through physical structures, the risk of inducing drug resistance can be effectively avoided.

[0059] In one embodiment, the inner wall surface of the nasal cavity support body has a biomimetic micro / nano structure based on gecko (Lucasium steindachneri) skin, damselfly wings, dragonfly wings, cicada wings, or lotus leaves. This can reduce the adhesion and reproduction of airborne bacteria on the shape memory nasal cavity support surface during respiration.

[0060] Specifically, the fabrication method of biomimetic micro / nano structures includes the following steps:

[0061] Collect gecko skin, damselfly wings, dragonfly wings, cicada wings, or lotus leaves, and spread them out on a glass slide with a film of water.

[0062] Using a syringe, silicone rubber is coated onto gecko skin, damselfly wings, dragonfly wings, cicada wings, or lotus leaves and quickly cured to form a rubber mold. After standing for 5 minutes, the gecko skin, damselfly wings, dragonfly wings, cicada wings, or lotus leaves are peeled off the mold with tweezers to obtain a biomimetic micro-nano structure mold.

[0063] The mold is attached to the planar unfolded shape of the inner wall of the nasal cavity stent body, heated to 176℃, held for 5 minutes, and then cooled to room temperature, so that the inner wall surface of the nasal cavity stent body has a biomimetic micro-nano structure.

[0064] In one embodiment, the shape memory nasal support further includes bee venom, turmeric extract, and zinc dioxide powder, wherein the turmeric extract and the zinc dioxide powder are uniformly distributed on the nasal support body, and the bee venom is distributed at the tip of the biomimetic micro / nano structure.

[0065] Bee venom is distributed only at the tip of the biomimetic micro-nano structure, which can effectively exert its bactericidal, anti-inflammatory and analgesic effects, while avoiding unnecessary harm to human health. The use of shape memory materials based on biomimetic micro-nano structures can improve the fit and stability of the support to the nasal cavity wall, thereby better supporting and stabilizing the nasal cavity.

[0066] For example, when a polylactic acid-based shape memory polymer is used, the mass ratio of polylactic acid, polyethylene glycol, graphene oxide, zinc dioxide powder, turmeric extract, and bee venom is 70:15:5:5:3.1:1.9.

[0067] Bee venom can inhibit the development of 20-30 Gram-negative and Gram-positive pathogenic microorganisms and is effective against penicillin-resistant Staphylococcus aureus. Bee venom is one of the most potent anti-inflammatory substances known to humankind, with an anti-inflammatory activity 100 times that of hydrocortisone. Turmeric extract is a diketone compound extracted from the rhizomes of some plants in the ginger and araceae families, possessing excellent anti-inflammatory and anti-cancer properties. Turmeric extract exerts its anti-cancer effects by inducing differentiation and apoptosis of malignant tumor cells and by inhibiting various stages of tumor growth. The anti-inflammatory activity of turmeric extract is comparable to that of steroidal and non-steroidal drugs, such as indomethacin and phenylbutazone, and is safe in most cases. Macrophages are crucial to the wound healing process by releasing factors that attract inflammatory cells to the wound site, stimulate granulation tissue formation, and enhance cell migration. By combining zinc dioxide and turmeric extract as alternative materials for wound dressings, studies have shown that this combination can accelerate the inflammatory phase of wound healing by increasing macrophage expression and decreasing the expression of Toll-like receptor 2, nuclear factor κB, and tumor necrosis factor α.

[0068] Combining bee venom, curcumin, and zinc dioxide powder in the preparation of wound dressings can produce the following synergistic effects:

[0069] Anti-inflammatory: Both bee venom and turmeric extract have excellent anti-inflammatory effects, which can effectively reduce inflammatory reactions and pain, while zinc dioxide powder can form a protective layer on the wound surface to prevent infection and further development of inflammation;

[0070] Accelerating healing: Both bee venom and turmeric extract can promote wound healing, stimulate wound tissue regeneration and repair, while zinc dioxide powder can help keep wounds moist and promote healing.

[0071] Antibacterial: Bee venom can inhibit the growth and reproduction of various bacteria, while turmeric extract can prevent pathogen infection, and zinc dioxide powder can also have a certain inhibitory effect on various microorganisms;

[0072] Therefore, the combination of these three materials can exhibit more outstanding effects in anti-inflammatory, accelerated healing and antibacterial properties, and is more effective than using any one of the materials alone.

[0073] In one embodiment, a method for preparing turmeric extract includes:

[0074] Fresh turmeric rhizomes harvested from 12-month-old turmeric plants are rinsed with tap water, drained, and cut into 5mm thick slices. They are then exposed to direct sunlight for 5 days to completely dehydrate, ground into turmeric rhizome powder, and then soaked in 99% ethanol. Hydrate 500 parts of turmeric rhizome powder with 500 parts of solvent (96% ethanol) in a beaker, flatten it, and mix it with the solvent until it is dissolved in 3000 parts of ethanol. After sealing, shake it on a digital display shaker at 50 rpm for 24 hours to obtain a liquid extract. Filter the liquid extract through a filter cloth and put it into a conical tube. Redissolve it in 3000 parts of ethanol for 24 hours. Mix the results of the first and second extractions together and evaporate them using a rotary evaporator at 60℃ for 6 hours until all the ethanol solvent has been separated. Finally, soak the extract in a water bath at 37℃ for 2 hours to obtain turmeric extract. Pour the turmeric extract into a beaker and concentrate it using a rotary evaporator until the volume is reduced to about 1 / 10 or 1 / 20 of the original volume. Transfer the concentrated turmeric extract to a desiccator and dry it at room temperature until the solvent is completely evaporated to obtain turmeric extract.

[0075] In addition, other methods for preparing turmeric extract include supercritical fluid extraction, microwave-assisted extraction, enzymatic extraction, or ultrasonic extraction.

[0076] Supercritical fluid extraction is a method that uses supercritical fluids (such as carbon dioxide) as solvents for extraction, and is characterized by high efficiency and environmental friendliness. Microwave-assisted extraction uses microwave radiation to heat plant samples and utilizes the resonance effect between microwaves and solvents to promote the extraction of substances, which can greatly improve extraction efficiency. Enzymatic extraction uses enzymes to hydrolyze and dissociate the active ingredients in turmeric, thereby improving extraction efficiency. Ultrasonic extraction utilizes the high energy, high frequency, and high amplitude characteristics of ultrasound to exert physical, chemical, and biological effects on the sample, thereby improving extraction efficiency.

[0077] Supercritical fluid extraction (SFE) is a highly efficient extraction method that utilizes the properties of supercritical fluids to extract target compounds from solid or liquid matrices under supercritical conditions. The following are the specific operational steps for supercritical fluid extraction of curcumin:

[0078] Equipment preparation: supercritical fluid extraction equipment, supercritical fluid storage tank, high-pressure pump, constant temperature water bath, data acquisition instrument, etc.

[0079] Sample preparation: Grind the turmeric sample into a fine powder and dry it to remove moisture and impurities, thus obtaining turmeric powder;

[0080] Sample loading: The dried turmeric powder is loaded into the extraction chamber of the supercritical fluid extractor;

[0081] Injecting supercritical fluid: CO 2 The gas is compressed and heated by a high-pressure pump, and then injected into a supercritical extractor to contact with turmeric powder and form supercritical CO2. 2 ;

[0082] Extraction process: Under certain temperature and pressure conditions, supercritical CO2... 2 It can extract the target components from turmeric powder; the extraction process takes a certain amount of time, usually several hours.

[0083] Separation and Collection: The material after supercritical extraction is passed through a pressure reducing device to remove supercritical CO2. 2 The target component was then separated from the sample. The target component was then collected in a collection bottle.

[0084] Evaporation to remove solvent: The resulting extract needs to be evaporated to remove supercritical CO2. 2 The final turmeric extract was obtained.

[0085] The specific steps for microwave-assisted extraction of curcumin are as follows:

[0086] The turmeric sample was ground into a fine powder, and the powder with uniform particles was sieved to obtain turmeric powder.

[0087] Mix turmeric powder and extract (such as ethanol, water, etc.) in a 5:8 ratio until homogeneous, and then pack into a sealed container.

[0088] Place the sealed container into the microwave-assisted extraction device and set appropriate extraction parameters, such as temperature, time, and microwave power.

[0089] Microwave power: typically set to 200-1000 watts, temperature: between 60-100℃, time: 30 minutes;

[0090] Turn on the microwave equipment to start the extraction. During the extraction process, the active ingredients in turmeric will be excited by microwave radiation and quickly dissolve into the extract.

[0091] After extraction, the sealed container is removed, and solid particles are filtered out with filter paper to obtain pure turmeric extract liquid. The extract is then concentrated and dried to obtain turmeric extract in powder or liquid form.

[0092] The specific steps for enzymatic extraction of turmeric are as follows:

[0093] Preparation of turmeric: First, peel the fresh turmeric and cut it into small pieces. Then wash it with water and cut it into fine turmeric powder for later use.

[0094] Enzyme selection: Choose the appropriate type of enzyme, commonly used ones include cellulase, amylase, protease, etc.

[0095] Preparation of hydrolysate: Add an appropriate amount of water to the enzymatic hydrolysis tank, and adjust the pH and temperature according to the characteristics of the selected enzyme;

[0096] Enzymatic hydrolysis: Add turmeric powder to the enzymatic hydrolysis tank, adjust the enzymatic hydrolysis conditions, add enzyme solution, and stir. The enzymatic hydrolysis time is usually 1-24 hours, depending on the experimental requirements.

[0097] Separation: After enzymatic hydrolysis, the mixture is filtered or centrifuged to obtain turmeric extract;

[0098] Purification: Unwanted impurities are precipitated with alcohol solvents, filtered, and then rinsed with distilled water to obtain pure turmeric extract;

[0099] Concentration: The extract was concentrated to the desired concentration using a rotary evaporator;

[0100] It is important to note that the specific settings for enzymatic hydrolysis conditions and steps need to be adjusted according to the characteristics of the selected enzyme and the experimental requirements.

[0101] The specific steps for ultrasonic extraction of turmeric are as follows:

[0102] Prepare turmeric samples: Grind the turmeric samples into powder, and then screen out particles within the target particle size range;

[0103] Prepare the extraction solution: Add the required extraction solvent (such as water, ethanol, etc.) to the extraction flask. The solvent ratio is usually 1:10-1:50 (sample mass / solvent volume).

[0104] Add turmeric sample: Add the turmeric sample to the extraction flask;

[0105] Ultrasonic treatment: Place the extraction bottle in an ultrasonic cleaner, set the appropriate ultrasonic power and treatment time. The power range is usually 100-500W and the treatment time is 10-60min.

[0106] Extraction separation: The liquid portion of the treated solution is separated using filter paper or a centrifuge;

[0107] Repeated extraction: If it is necessary to increase the extraction rate, steps 3-5 can be repeated multiple times;

[0108] Concentrate the extract: Concentrate the extract to the desired concentration using a rotary evaporator or other methods;

[0109] Further processing: If necessary, the target compound can be further purified by methods such as column chromatography, thin-layer chromatography, and high-performance liquid chromatography.

[0110] In another embodiment, the outer and inner sides of the nasal cavity support body are both covered with hydrogel layers, that is, the outer side of the nasal cavity support body is covered with a first hydrogel layer and the inner side is covered with a second hydrogel layer. The first hydrogel layer can improve the adhesion performance when in contact with the nasal cavity, and the surface of the second hydrogel layer is provided with a biomimetic micro-nano structure of Australian gecko skin, which can better achieve the physical protection function.

[0111] In one embodiment, the initial shape of the nasal support body has a thickness of 0.2-0.4 mm, a diameter of 5-10 mm, and a length of 13-16 mm. The size of the hydrogel layer matches the size of the nasal support body, and the thickness of the hydrogel layer is 0.5 mm.

[0112] It should be understood that the size of the nasal support body can be adjusted according to the specific condition of the user's nasal cavity.

[0113] Another embodiment of the present invention provides a method for fabricating a shape memory nasal cavity support, used to fabricate the shape memory nasal cavity support as described above, such as... Figure 5 As shown, it includes the following steps:

[0114] Step S1: Construct a three-dimensional structural model of the initial shape of the shape memory nasal cavity support;

[0115] Step S2: Prepare shape memory polymer, and print the shape memory polymer according to the three-dimensional structural model using 4D printing method to obtain the nasal cavity support body with the initial shape;

[0116] Step S3: Prepare hydrogel, coat the hydrogel onto the outside of the nasal cavity support body of the initial shape, and form a hydrogel layer on the outside of the nasal cavity support body to obtain the shape memory nasal cavity support of the initial shape.

[0117] Step S4: Heat the initial shape of the shape memory nasal cavity support to above the glass transition temperature, apply external force, and then cool it to below room temperature to obtain a temporary shape of the shape memory nasal cavity support.

[0118] In step S1, three-dimensional structural data is obtained by precisely scanning the user's nasal cavity. The model is then created using UG 3D modeling software. First, the three-dimensional geometric shape of the user's nasal mucosa tissue in its normal state is determined, and a shell structure without holes is designed. Then, based on the deformation behavior of the shape memory nasal stent during implantation, the shape of the frame grid unit is designed, such as a rhombus or a rhombus variant with four curved sides, to obtain an initial structure that is easy to implant and can withstand the radial load caused by mucosal swelling after implantation.

[0119] 4D printing refers to 3D printing using shape memory materials. Relying on the controllable dynamic evolution of smart materials such as shape memory polymers, it is possible to obtain dynamic products whose shape changes according to the design under different environmental conditions.

[0120] In step S2, the shape memory polymer is printed according to the three-dimensional structural model using either fused deposition modeling (FDM) or direct write printing (DIW) to obtain the nasal cavity support body with the initial shape.

[0121] In the fused deposition method, shape memory polymer filaments are fed into a nozzle using a hydraulic or electric motor-controlled clamp. The filaments are then heated to a molten state and extruded through the nozzle onto a platform using mechanical force to create planar layers. The next planar layer is extruded onto the previous planar layer to form a three-dimensional structure. The structure of each extruded layer is solidified through mechanisms such as crystallization, rearrangement, chain take-off, non-covalent bond recovery, or chemical cross-linking.

[0122] When using the direct-write printing method, shape memory polymer ink is extruded through a nozzle under pressure, and the geometric shape is created layer by layer under computer control. The extruded ink is then cured by photopolymerization or thermal curing.

[0123] In one embodiment, the printing temperature is 240°C, the printing speed is 20 mm / s, the print bed temperature is 40°C, the layer height is 0.8 mm, and the fill rate is 60%. During the printing process, the cooling fan is turned on to accelerate the cooling of the printed object to avoid problems such as deformation or warping.

[0124] In one embodiment, to facilitate the coating of a hydrogel layer on the nasal cavity support body, the unfolded shape of the nasal cavity support body under the initial shape is first obtained by 4D printing.

[0125] Furthermore, to enhance the physical antibacterial properties of the shape memory nasal cavity stent, a biomimetic micro / nanostructure mold can be created by collecting naturally shed skin from Australian geckos. The unfolded shape of the nasal cavity stent body is then attached to the mold, heated and kept at a constant temperature, and finally cooled to room temperature, resulting in a planar unfolded shape with a biomimetic micro / nanostructure on its surface.

[0126] In one embodiment, in step S3, a hydrogel is prepared using N-isopropylacrylamide, linear methylcellulose, and N,N'-methylenebisacrylamide. The hydrogel is coated on the side of the unfolded planar shape that does not have biomimetic micro / nano structures, and then the unfolded planar shape is rolled up to form a shape memory nasal cavity support of the initial shape.

[0127] Specifically, step S3 includes:

[0128] Step S31: Dissolve 300 parts of N-isopropylacrylamide in 500 parts of water to form an N-isopropylacrylamide solution, remove air bubbles under vacuum, dissolve 100 parts of linear methylcellulose in 800 parts of water to form a linear methylcellulose solution, remove air bubbles under vacuum, mix the N-isopropylacrylamide solution and the linear methylcellulose solution evenly, add 0.167 parts of N,N'-methylenebisacrylamide, put it in a container and seal it, and shake it in an ultrasonic cleaner for 6 hours to remove air bubbles, to obtain a mixed solution;

[0129] Step S32: The mixed solution is coated on the outer side of the nasal cavity support body of the initial shape to form a coating with a thickness of about 0.5 mm. The coating is polymerized for 5 h under nitrogen atmosphere at 10°C and ultraviolet light at 360 nm-370 nm to form a hydrogel layer, thereby obtaining the shape memory nasal cavity support of the initial shape.

[0130] To enable the shape memory nasal stent to deform not only under temperature stimulation but also under magnetic field and / or light stimulation, one or more of the following are added during the preparation of the shape memory polymer and the hydrogel: iron(II,III) oxide, iron oxide, gold nanoparticles, silver nanoparticles, polypyrrole, graphene, or graphene oxide. These substances are magnetic or photosensitive, and their addition enables the shape memory nasal stent to deform under magnetic field or light stimulation. Among them, gold nanoparticles and silver nanoparticles are inorganic photothermal agents. When the frequency of vibration of a large number of freely conducted electrons in the particles is the same as the frequency of the incident light wave, a plasma oscillation effect will occur, resulting in a strong absorption peak. Polypyrrole is an organic polymer photothermal agent with excellent photothermal effect and photostability. Graphene and graphene oxide have a light absorption rate of up to 40% in the far-infrared and microwave bands. When graphene or graphene oxide absorbs light, the generated electron-hole pairs will quickly interact with other electron-hole pairs, leading to an increase in the overall temperature of the electrons. Since the human body has a low absorption rate of near-infrared light, near-infrared light can be used as a laser source for stimulation, thereby reducing damage to the nasal cavity.

[0131] For example, the mass ratio of magnetic and / or photosensitive substances added to the shape memory polymer and hydrogel is 5-10%.

[0132] It should be understood that, in order to enable the shape memory nasal stent to deform synchronously when stimulated, it is preferable to add the same substance to both the shape memory polymer and the hydrogel, and maintain the same addition ratio.

[0133] In step S4, the shape memory nasal cavity support is heated to above the glass transition temperature, or stimulated by a magnetic field or light to apply external force to form a temporary shape memory nasal cavity support. The support is then rapidly cooled to below room temperature to solidify the temporary shape memory nasal cavity support.

[0134] It should be noted that the term "temporary shape" does not mean temporary or short-lived. It refers to the ability of a technology to maintain a temporary shape without external stimuli. The term is used to distinguish the initial shape from the shape after implantation into the nasal cavity.

[0135] This invention also provides a method for using a shape memory nasal cavity support, based on the above-described shape memory nasal cavity support, such as... Figure 6 As shown, it includes:

[0136] Step T1: Before implantation into the nasal cavity, apply temperature, electromagnetic or light stimulation to the initial shape memory nasal cavity support, and use external force to transform the initial shape shape memory nasal cavity support into a temporary shape shape memory nasal cavity support.

[0137] Step T2: The temporary shape memory nasal support is implanted into the user's nasal cavity. Stimulation is applied to the temporary shape memory nasal support to restore it to the initial shape until it fits the user's nasal mucosa.

[0138] Step T3: When it is necessary to remove the shape memory nasal support from the nasal cavity, apply the same stimulation to the shape memory nasal support again, and use external force to transform the shape memory nasal support into the temporary shape, and then remove it.

[0139] The method of using the shape memory nasal stent provided in this invention involves deforming the shape memory nasal stent into a smaller temporary shape before implantation to avoid damage to the nasal mucosa during implantation. After implantation, the shape memory nasal stent can be transformed back to its initial shape by applying stimulation until it adheres to the nasal mucosa, providing good support and resisting complications such as breathing difficulties and sleep apnea caused by swelling and deformation of the nasal mucosa. Because it uses shape memory material, the shape memory nasal stent can gradually degrade within the nasal cavity. If it needs to be removed midway, the shape memory nasal stent can be restored to its temporary shape by stimulating it again and applying external force, avoiding secondary harm during removal.

[0140] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Experimental methods in the following embodiments, unless otherwise specified, are generally performed according to the conditions recommended by the manufacturer.

[0141] Example 1

[0142] 1.1 Mix 70% polylactic acid, 15% polyethylene glycol, 5% iron oxide, and 10% hydrocortisone according to the mass ratio. Preheat the extruder to 180°C, adjust the traction machine speed, and draw out a filament with a diameter of 1.75mm. Install the collected filament onto the 3D printer and print the planar unfolded shape of the nasal cavity support body under the initial shape using the DIW method.

[0143] 1.2 Collect naturally shed skin from Australian geckos and spread it onto a glass slide with a water film. Use a syringe to apply silicone rubber to the Australian gecko skin and allow it to solidify rapidly to form a rubber mold. After five minutes, use a pair of tweezers to peel the Australian gecko skin off the mold to obtain a biomimetic micro-nano structure mold. Attach the mold to the above-mentioned planar unfolded shape, heat it to 176°C, hold it for 5 minutes, and cool it to room temperature to obtain a planar unfolded shape with a biomimetic micro-nano structure on the surface.

[0144] 1.3 Dissolve 300 parts of N-isopropylacrylamide in 500 parts of water to form an N-isopropylacrylamide solution. Remove air bubbles under vacuum. Dissolve 100 parts of linear methylcellulose in 800 parts of water to form a linear methylcellulose solution. Remove air bubbles under vacuum. Mix the two solutions evenly. Add 0.167 parts of N,N'-methylenebisacrylamide. Place the mixture in a sealed container and agitate in an ultrasonic cleaner for 3 hours to remove air bubbles. Then, coat the mixed solution onto the side of the planar unfolded shape without biomimetic micro / nano structures to form a coating with a thickness of 0.5 mm. Polymerize under a nitrogen atmosphere at 10°C and under 365 nm ultraviolet light for 5 hours to form a hydrogel layer.

[0145] 1.4. The structure obtained in step 1.3 is rolled up on both sides so that the hydrogel layer is on the outside and the biomimetic micro-nano structure is on the inside. The hydrogel layer is melted and bonded together using a resistance wire heater to form a shape memory nasal cavity support with the initial shape.

[0146] 1.5. Heat the initial shape memory nasal cavity support to 60°C, apply external force, and quickly cool it to below room temperature to obtain a temporary shape memory nasal cavity support.

[0147] Example 2

[0148] 2.1 Mix 70% polylactic acid, 15% polyethylene glycol, 5% gold nanoparticles, and 10% aspirin according to the mass ratio. Preheat the extruder to 180°C, adjust the traction machine speed, and draw out a filament with a diameter of 1.75 mm. Install the collected filament onto the 3D printer and print the planar unfolded shape of the nasal cavity support body under the initial shape using the FDM method.

[0149] 2.2 Collect naturally shed skin from Australian geckos and spread it onto a glass slide with a water film. Use a syringe to apply silicone rubber to the Australian gecko skin and allow it to solidify rapidly to form a rubber mold. After five minutes, use a pair of tweezers to peel the Australian gecko skin off the mold to obtain a biomimetic micro-nano structure mold. Attach the mold to the above-mentioned planar unfolded shape, heat it to 176°C, hold it for 5 minutes, and cool it to room temperature to obtain a planar unfolded shape with a biomimetic micro-nano structure on the surface.

[0150] 2.3 Dissolve 300 parts of N-isopropylacrylamide in 500 parts of water to form an N-isopropylacrylamide solution. Remove air bubbles under vacuum. Dissolve 100 parts of linear methylcellulose in 800 parts of water to form a linear methylcellulose solution. Remove air bubbles under vacuum. Mix the two solutions evenly. Add 0.167 parts of N,N'-methylenebisacrylamide. Place the mixture in a sealed container and agitate in an ultrasonic cleaner for 3 hours to remove air bubbles. Then, coat the mixed solution onto the side of the planar unfolded shape without biomimetic micro / nano structures to form a coating with a thickness of 0.5 mm. Polymerize under a nitrogen atmosphere at 10°C and under 365 nm ultraviolet light for 5 hours to form a hydrogel layer.

[0151] 2.4. The structure obtained in step 2.3 is rolled up on both sides so that the hydrogel layer is on the outside and the biomimetic micro-nano structure is on the inside. The hydrogel layer is melted and bonded together using a resistance wire heater to form a shape memory nasal cavity support with the initial shape.

[0152] 2.5. Heat the initial shape memory nasal cavity support to 60°C, apply external force, and quickly cool it to below room temperature to obtain a temporary shape memory nasal cavity support.

[0153] Example 3

[0154] 3.1 Mix 70% polylactic acid, 15% polyethylene glycol, 5% graphene oxide, and 10% ketorolac according to the mass ratio. Preheat the extruder to 180°C, adjust the traction machine speed, and draw out a filament with a diameter of 1.75 mm. Install the collected filament onto the 3D printer and print the planar unfolded shape of the nasal cavity support body under the initial shape using the DIW method.

[0155] 3.2 Collect naturally shed skin from Australian geckos and spread it onto a glass slide with a water film. Use a syringe to apply silicone rubber to the Australian gecko skin and allow it to solidify rapidly to form a rubber mold. After five minutes, use a pair of tweezers to peel the Australian gecko skin off the mold to obtain a biomimetic micro-nano structure mold. Attach the mold to the above-mentioned planar unfolded shape, heat it to 176°C, hold it for 5 minutes, and cool it to room temperature to obtain a planar unfolded shape with a biomimetic micro-nano structure on the surface.

[0156] 3.3 Dissolve 300 parts of N-isopropylacrylamide in 500 parts of water to form an N-isopropylacrylamide solution. Remove air bubbles under vacuum. Dissolve 100 parts of linear methylcellulose in 800 parts of water to form a linear methylcellulose solution. Remove air bubbles under vacuum. Mix the two solutions evenly. Add 0.167 parts of N,N'-methylenebisacrylamide. Place the mixture in a sealed container and agitate in an ultrasonic cleaner for 3 hours to remove air bubbles. Then, coat the mixed solution onto the side of the planar unfolded shape without biomimetic micro / nano structures to form a coating with a thickness of 0.5 mm. Polymerize under a nitrogen atmosphere at 10°C and under 365 nm ultraviolet light for 5 hours to form a hydrogel layer.

[0157] 3.4. The structure obtained in step 3.3 is rolled up on both sides so that the hydrogel layer is on the outside and the biomimetic micro-nano structure is on the inside. The hydrogel layer is melted and bonded together using a resistance wire heater to form a shape memory nasal cavity support with the initial shape.

[0158] 3.5. Heat the initial shape memory nasal cavity support to 60°C, apply external force, and quickly cool it to below room temperature to obtain a temporary shape memory nasal cavity support.

[0159] Example 4

[0160] 4.1 Mix 70% polylactic acid, 15% polyethylene glycol, 5% graphene oxide and 10% zinc dioxide powder according to the mass ratio, preheat the extruder to 180°C, adjust the traction machine speed, and draw out a filament with a diameter of 1.75mm. Install the collected filament onto the 3D printer and print the planar unfolded shape of the nasal cavity support body under the initial shape using the DIW method.

[0161] 4.2. Attach the naturally shed skin of an Australian gecko onto a planar unfolded shape, heat it to 176℃, hold for 5 minutes, and cool it to room temperature to obtain a planar unfolded shape with a biomimetic micro-nano structure on the surface.

[0162] 4.3 Dissolve 300 parts of N-isopropylacrylamide in 500 parts of water to form an N-isopropylacrylamide solution. Remove air bubbles under vacuum. Dissolve 100 parts of linear methylcellulose in 800 parts of water to form a linear methylcellulose solution. Remove air bubbles under vacuum. Mix the two solutions evenly. Add 0.167 parts of N,N'-methylenebisacrylamide. Place the mixture in a sealed container and agitate in an ultrasonic cleaner for 3 hours to remove air bubbles. Then, coat the mixed solution onto the side of the planar unfolded shape without biomimetic micro / nano structures to form a coating with a thickness of 0.5 mm. Polymerize under a nitrogen atmosphere at 10°C and under 365 nm ultraviolet light for 5 hours to form a hydrogel layer.

[0163] 4.4. The structure obtained in step 4.3 is rolled up on both sides so that the hydrogel layer is on the outside and the biomimetic micro-nano structure is on the inside. The hydrogel layer is melted and bonded together using a resistance wire heater to form a shape memory nasal cavity support with the initial shape.

[0164] 4.5. Heat the initial shape memory nasal cavity support to 60°C, apply external force, and quickly cool it to below room temperature to obtain a temporary shape memory nasal cavity support.

[0165] Example 5

[0166] 5.1 Mix 70 parts polylactic acid, 15 parts polyethylene glycol, 5 parts graphene oxide, 5 parts zinc dioxide powder and 3.1 parts turmeric extract according to the mass ratio. Preheat the extruder to 180°C, adjust the traction machine speed, and pull out a filament with a diameter of 1.75 mm. Install the collected filament onto the 3D printer and print the planar unfolded shape of the nasal cavity support body under the initial shape using the DIW method.

[0167] 5.2. Naturally shed skin from an Australian gecko is attached to a planar unfolded shape, heated to 176℃ and held for 5 minutes, then cooled to room temperature to obtain a planar unfolded shape with a biomimetic micro / nano structure on its surface. The resulting planar unfolded shape with the biomimetic micro / nano structure is then sterilized under an ultraviolet germicidal lamp.

[0168] 5.3 Dilute the bee venom with 96% ethanol to adjust the concentration to 0.05 mg / mL;

[0169] 5.4. According to the ratio, drop the prepared bee venom solution onto the tip of the biomimetic micro / nano structure in a planar unfolded shape, and let it diffuse and penetrate naturally to the tip of the biomimetic micro / nano structure.

[0170] 5.5 Dissolve 300 parts of N-isopropylacrylamide in 500 parts of water to form an N-isopropylacrylamide solution. Remove air bubbles under vacuum. Dissolve 100 parts of linear methylcellulose in 800 parts of water to form a linear methylcellulose solution. Remove air bubbles under vacuum. Mix the two solutions evenly. Add 0.167 parts of N,N'-methylenebisacrylamide. Place the mixture in a sealed container and place it in an ultrasonic cleaner for 3 hours to remove air bubbles. Coat the other side of the flat, unfolded shape with the obtained hydrogel layer to form a hydrogel layer with a thickness of 0.5 mm.

[0171] 5.6. Curl up both sides of the structure obtained in step 5.5 so that the tip of the biomimetic micro-nano structure faces the hydrogel layer. Melt it with a resistance wire heater and bond it together to form a shape memory nasal cavity support with the initial shape.

[0172] 5.7. Heat the initial shape memory nasal cavity support to 60°C, apply external force, and quickly cool it to below room temperature to obtain a temporary shape memory nasal cavity support.

[0173] While the disclosure is as stated above, its scope of protection is not limited thereto. Those skilled in the art can make various changes and modifications without departing from the spirit and scope of this disclosure, and all such changes and modifications will fall within the protection scope of this invention.

Claims

1. A shape memory nasal cavity support, characterized in that, The device includes a nasal cavity support body and a hydrogel layer, the hydrogel layer covering the outer side of the nasal cavity support body. The nasal cavity support body has a mesh-like three-dimensional structure and is made of shape memory polymer. The shape memory nasal cavity support includes a temporary shape and an initial shape. Both the initial shape and the temporary shape of the shape memory nasal cavity support are cylindrical. The initial shape of the shape memory nasal cavity support matches the size of the nasal cavity, and the diameter of the initial shape of the shape memory nasal cavity support is larger than the diameter of the temporary shape of the shape memory nasal cavity support. When the shape memory nasal cavity support is stimulated by external factors, it transforms from the temporary shape to the initial shape. The inner wall surface of the nasal cavity support body has a biomimetic micro-nano structure based on gecko skin, damselfly wings, dragonfly wings, cicada wings or lotus leaves. The shape memory nasal cavity support also includes bee venom, turmeric extract and zinc dioxide powder, wherein the turmeric extract and the zinc dioxide powder are uniformly distributed on the nasal cavity support body, and the bee venom is distributed at the tip of the biomimetic micro-nano structure.

2. The shape memory nasal cavity support according to claim 1, characterized in that, The frame grid units of the mesh three-dimensional structure are rhomboid or rhomboid variants with curved four sides.

3. The shape memory nasal cavity support according to claim 1, characterized in that, The shape memory polymer includes one or more of the following: polylactic acid-based, polycaprolactone-based, polyethylene glycol-based, alginate-based, polydopamine-based, gelatin-based, polydopamine-based, polyvinyl alcohol-based, hydroxymethyl cellulose-based, polyacrylamide-based, and polyacrylate-based shape memory polymers.

4. The shape memory nasal cavity support according to claim 1, characterized in that, It also includes a drug loaded on the nasal stent body or the hydrogel layer, the drug including one or more of aspirin, metamizole, acetaminophen, indomethacin, piroxicam, ketorolac, cortisone, hydrocortisone, dexamethasone, aminoglycoside broad-spectrum antibiotics, tumor necrosis factor inhibitors, growth factors and immunomodulators.

5. A method for preparing a shape memory nasal cavity stent, used to prepare the shape memory nasal cavity stent as described in any one of claims 1-4, characterized in that, Includes the following steps: Step S1: Construct a three-dimensional structural model of the initial shape of the shape memory nasal cavity support; Step S2: Prepare shape memory polymer, and print the shape memory polymer according to the three-dimensional structural model using 4D printing method to obtain the nasal cavity support body with the initial shape; Step S3: Prepare hydrogel, coat the hydrogel onto the outside of the nasal cavity support body of the initial shape, and form a hydrogel layer on the outside of the nasal cavity support body to obtain the shape memory nasal cavity support of the initial shape. Step S4: Heat the initial shape of the shape memory nasal cavity support to above the glass transition temperature, apply external force, and then cool it to below room temperature to obtain a temporary shape of the shape memory nasal cavity support.

6. The method for preparing the shape memory nasal cavity support according to claim 5, characterized in that, One or more of the following are added during the preparation of the shape memory polymer and the hydrogel: iron oxide, iron oxide, gold nanoparticles, silver nanoparticles, polypyrrole, graphene, or graphene oxide.

7. The method for preparing the shape memory nasal cavity support according to claim 5, characterized in that, Step S3 includes: Step S31: Dissolve 300 parts of N-isopropylacrylamide in 500 parts of water to form an N-isopropylacrylamide solution, remove air bubbles under vacuum, dissolve 100 parts of linear methylcellulose in 800 parts of water to form a linear methylcellulose solution, remove air bubbles under vacuum, mix the N-isopropylacrylamide solution and the linear methylcellulose solution evenly, add 0.167 parts of N,N'-methylenebisacrylamide, put it in a container and seal it, and shake it in an ultrasonic cleaner for 6 hours to remove air bubbles, to obtain a mixed solution; Step S32: The mixed solution is coated on the outer side of the nasal cavity support body of the initial shape to form a coating with a thickness of about 0.5 mm. The coating is polymerized for 5 hours under nitrogen atmosphere at 10°C and ultraviolet light at 360 nm-370 nm to form a hydrogel layer, thereby obtaining the shape memory nasal cavity support of the initial shape.

Images