A flexible, strong and tough drainage member with high biocompatibility, drainage device

Abstract

This invention provides a flexible, strong, and highly biocompatible drainage component and device, relating to the technical field of medical products. The drainage component has an overall strip-like or tubular structure, and its inner wall has a repeating array structure, including but not limited to conical microgrooves extending in the same direction. The drainage component is composed of a hydrophilic phase made of chain-like polymer and ordered submicron hydrophobic microparticles therein. The microgroove structure in the drainage component is obtained through in-situ polymerization using a solution method and a replica template. After demolding, it undergoes in-situ toughening treatment to oriented the hydrophobic microregions, ultimately obtaining a drainage component and device that combines flexibility, strength, and high biocompatibility. The flexible, strong, and highly biocompatible drainage component and device provided in this application solves the problems of difficulty in achieving both flexibility and strength in existing hydrogel microstructure catheter fabrication technologies, as well as difficulties in demolding during the molding process.

Description

Technical Field

[0001] This invention relates to the technical field of medical devices, and in particular to a flexible, strong, and highly biocompatible drainage component and drainage device. Background Technology

[0002] Draining exudate, blood, and other biological fluids from wounds is an unavoidable part of clinical treatment. Although wound exudate can provide nutrients and a microenvironment for cell growth, excessive exudate can macerate the wound, promote bacterial growth, and further worsen the wound condition. Therefore, wound dressings are necessary to drain wound exudate, isolate the wound from external bacteria, microorganisms, and other foreign substances, and provide a favorable environment for wound healing.

[0003] Clinically, large-area wounds or surgical wounds that generate a large amount of biological fluid are often encountered. Absorbent wound dressings based on fibers, gels, and foams cannot handle such wounds due to their limited absorption capacity. Clinically, drainage tubes with external negative pressure suction devices are commonly used to drain these wounds. The external negative pressure device creates a pressure gradient at both ends of the drainage tube, enabling directional drainage of wound exudate from the wound to the outside. However, such devices rely on an external negative pressure generator, resulting in poor portability, high energy consumption, intense pain, and the potential for improper negative pressure to damage wound tissue and further worsen the wound. Currently, a type of drainage tube based on surface microstructures has been reported. It can achieve drainage without external energy, can drain exudates with higher viscosity, and does not require a closed environment like negative pressure drainage devices. However, constructing the microstructure within the drainage tube is very difficult, often relying on 3D printing, which results in poor flexibility. Using materials to create templates is another method, but the microstructure is easily damaged during demolding, and the material has poor strength and is prone to breakage.

[0004] Therefore, there is an urgent need to provide drainage devices that can meet clinical treatment needs, do not require negative pressure drainage, and are biocompatible, flexible, and strong. Summary of the Invention

[0005] The purpose of this application is to provide a flexible, strong, and highly biocompatible drainage device that combines flexibility, strength, and good biocompatibility.

[0006] Another object of this application is to provide a drainage device.

[0007] Firstly, based on the aforementioned technical problems, this application provides a flexible, strong, and highly biocompatible drainage device. The drainage device is a strip-shaped or tubular structure, and at least one surface of the drainage device is arrayed with a plurality of conical microstructures inclined in the same direction. The drainage device material includes a continuous hydrophilic phase and ordered distributed hydrophobic microregions, wherein the hydrophilic phase gel skeleton presents an ordered strip shape, and the hydrophobic microregions are attached to the hydrophilic strips and distributed in an ordered strip shape. Wherein, the hydrophilic phase is a gel skeleton formed by the polymerization of hydrophilic chain polymers, and the hydrophobic micro-regions are micro-regions formed by submicron-sized hydrophobic phase particles distributed on the gel skeleton; The water content of the drainage component when it is fully swollen in water is 31%-51%, the tensile strength is not less than 2.1 MPa, and the elongation at break is 350%-560%.

[0008] Furthermore, in some embodiments provided in this application, the diameter of the hydrophobic phase microregion is less than 3 μm and the interval between adjacent hydrophobic phase microregions is less than 10 μm in the strip-shaped direction; in the direction perpendicular to the strip, the interval between adjacent hydrophobic phase microregions is not higher than 10 μm.

[0009] Furthermore, in some embodiments provided in this application, in the fully swollen draining element, the mass fraction of the hydrophilic phase is 5%-40%, the mass fraction of the hydrophobic phase is 20%-45%, and the mass ratio of the hydrophilic phase to the hydrophobic phase is 2:1 to 1:3.

[0010] Furthermore, in some embodiments provided in this application, the hydrophilic phase is selected from one or more of polyvinyl alcohol, sodium alginate, hyaluronic acid, and gelatin; the hydrophobic phase is selected from one or more of medical-grade anhydrous lanolin, food-grade beeswax, medical silicone gel, polyolefin elastomer, plant-based glyceryl stearate, petrolatum, long-chain alkanes, and solid oils.

[0011] Furthermore, in some embodiments provided in this application, when the hydrophilic phase is a non-amphiphilic polymer, the drainage material further includes a biocompatible surfactant, wherein the surfactant satisfies the following conditions: HLB value of 8.0-14.0; cytotoxicity level of no greater than grade 1 according to ISO 10993-5:2009; and hemolysis rate of less than 5% as tested according to ISO 10993-4:2017.

[0012] Furthermore, in some embodiments provided in this application, the surfactant is selected from one or more of the following: lecithin, phosphatidylcholine, phosphatidylethanolamine, Tween 80, Tween 20, gelatin derivatives, and albumin.

[0013] Furthermore, in some embodiments provided in this application, the draining element does not include any of the initiators or catalysts.

[0014] Furthermore, in some embodiments provided in this application, the drainage element does not contain water-soluble compounds with a molecular weight not exceeding 500.

[0015] Furthermore, in some embodiments provided in this application, the hydrophilic phase is cured by physical crosslinking or ionic crosslinking.

[0016] Furthermore, in some embodiments provided in this application, the cross-section of the wound drainage material is smooth and flat when observed under an electron microscope at 2000x magnification, and no pore structure is observed.

[0017] Furthermore, in some embodiments provided in this application, the drainage element material is obtained by polymerizing a prepolymer liquid comprising the following components: With the mass fraction of the prepolymer liquid being 100%, the mass fraction of the hydrophobic phase in the prepolymer liquid is 5%~25%; the mass fraction of the aqueous phase is 75~95%; and the mass percentage of the hydrophilic chain polymer material in the aqueous phase of the prepolymer liquid is not higher than 20%.

[0018] Furthermore, in some embodiments provided in this application, the conical microstructure is obtained by in-situ polymerization of the material of the drain element on a template with the corresponding microstructure, and the loss rate during demolding and toughening processes when the drain element is formed is not higher than 4.2%.

[0019] Furthermore, in some embodiments provided in this application, the length of the conical microstructure in the direction of the tube axis of the drainage element is 200μm~500μm, and the length in the direction perpendicular to the tube axis is 120μm~300μm.

[0020] Secondly, this application also provides a drainage device, including the flexible, strong, and highly biocompatible drainage element described in the first aspect.

[0021] This application provides a drainage device that can achieve active drainage using Laplace pressure, eliminating the need for a separate drainage power supply device and eliminating reliance on the device's placement and installation method. Furthermore, the drainage device utilizes a highly biocompatible hydrophilic phase to form a gel framework, along with hydrophobic particles distributed within the gel framework, creating a unique gel structure with a continuous aqueous phase framework and discontinuously dispersed hydrophobic particles. This not only solves the problem of difficult demolding of aqueous gels in existing technologies but also improves the gel's strength and flexibility, achieving a combination of flexibility, strength, moldability, and biocompatibility. The drainage device provided in this application is a flexible drainage device, causing minimal irritation to the wound, exhibiting good flexibility, and being resistant to breakage and damage. This is because the drainage component uses an emulsion formed from a biocompatible hydrophobic phase and an aqueous phase, which is solidified through freezing and thawing without a crosslinking agent to obtain the molded drainage tube and the microstructure on the drainage tube. There is no need to set up a separate device or step for forming the microstructure, which solves the disadvantage of the existing technology that uses crosslinking agent polymerization, resulting in the difficulty of demolding and thus the difficulty in maintaining the microstructure. This improves the consistency of the microstructure in the drainage component. In addition, the gel volume change is small during the molding, curing and toughening process of this preparation method, which is conducive to the maintenance of the microstructure during the toughening process and avoids the high deformation rate caused by volume change during the toughening process, which would affect the active drainage effect of the drainage component. Attached Figure Description To more clearly illustrate the technical solutions in the specific embodiments of this application or the prior art, the drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of this application. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0022] Figure 1 This is a schematic diagram of the flexible, strong, and highly biocompatible drainage device and its inner wall obtained in Example 1 of this application. Figure 2 Scanning electron microscope (SEM) images of the drainage material obtained in Comparative Example 1, Comparative Example 2, and Example 1, respectively, showing the drainage material with flexible, strong, and highly biocompatible properties. Figure 3 This is a confocal microscope image of the bulk microstructure of the wound drainage material obtained in Example 1 of this application; Figure 4 The changes in the microstructure of the gel materials obtained in Example 8 and Comparative Example 1 of this application before and after toughening are shown. Figure 5 This is a bar chart showing the elastic modulus of the drainage element materials obtained in Embodiment 8, Comparative Example 1, and Comparative Example 2 of this application; Figure 6 This is a bar chart showing the tensile strength of the drainage element materials obtained in Examples 1 to 5 and Comparative Example 7 of this application; Figure 7 This is a bar chart showing the tensile strength of the drainage element materials obtained in Examples 1, 6-8, and Comparative Example 8 of this application; Figure 8 The tensile strength histograms of the drainage element materials obtained in Examples 9-11, Comparative Examples 9 and 12 of this application are shown. Figure 9 The bar charts are of the mass changes of the drainage element materials obtained in Examples 1, 6-8, and Comparative Examples 1 and 8 of this application before and after toughening. Figure 10 The bar chart shows the volume change of the drainage material before and after toughening in Examples 1, 6-8, and Comparative Examples 1 and 8 of this application. Figure 11 The bar chart shows the cell viability at 24h and 48h obtained from the biosafety test (CCK-8 staining method) of the drainage devices obtained in Example 1, Comparative Example 1, and Comparative Example 2 of this application. Figure 12 Fluorescence images obtained at 24h and 48h from the biosafety test (cell live / dead staining method) of the drainage devices obtained in Example 1, Comparative Example 1, and Comparative Example 2 of this application. Detailed Implementation

[0023] The technical solutions of this application will be clearly and completely described below with reference to the embodiments. Obviously, the described embodiments are only some embodiments of this application, not all embodiments. Based on the embodiments of this application, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this application.

[0024] The technical solution of the present invention will be clearly and completely described below with reference to the embodiments. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0025] The following disclosure provides many different embodiments or examples for implementing different structures of this application. To simplify the disclosure, specific examples of components and arrangements are described below. Of course, these are merely examples and are not intended to limit the scope of this application. Furthermore, reference numerals and / or letters may be repeated in different examples; such repetition is for simplification and clarity and does not in itself indicate a relationship between the various embodiments and / or arrangements discussed. In addition, examples of various specific materials are provided in this application, but those skilled in the art will recognize the application of other processes and / or the use of other materials.

[0026] The existing active drainage methods include the following: (1) using the water absorption property of the material itself to generate suction drainage, such as gauze, to achieve active drainage; (2) using the surface structure design of the material to achieve liquid drainage, such as capillary effect drainage, and the Laplace pressure difference formed by micro-nano structure design to achieve directional movement of liquid. Among them, the construction of microstructure design that can generate Laplace pressure difference on the material is a key link to achieve the active drainage effect. When a tubular drainage component is used, the complex microstructure is set on the inner wall of the tube, and the diameter of the drainage tube is small. It is extremely difficult to enter the tube for fine processing after the tube is formed. Therefore, it is preferred that the formation of the drainage tube and the microstructure are formed at the same time. The existing methods for constructing tubular materials with complex microstructure inner wall are mainly 3D printing direct construction or template replication method. However, the applicant discovered that currently, when using 3D printing technology to directly construct drainage components, rigid resins are mainly used. When using flexible resins to construct drainage components, if a microcavity structure needs to be formed on a surface, the formed microcavity structure is very easy to become clogged. Moreover, drainage components made of rigid resins, especially tubular drainage tubes, have poor flexibility, which limits their practical use. When using chemically cross-linked materials for template replication, such as photocatalytic cross-linked gels, the material is prone to forming certain valence bonds with the surface of the 3D printing template during molding, leading to difficulty in demolding and easy demolding damage. When choosing physically cross-linked materials for replication, if the material's elastic modulus is too high, the molded tube will generate a large frictional force with the microstructure on the template during demolding, hindering demolding and easily damaging the tube and surface microstructure. If the material's elastic modulus is too low, the prepared drainage tube is easily damaged during use.

[0027] Based on this, this application provides a flexible, strong, and highly biocompatible drainage device, such as... Figure 1 As shown, the drainage element is a strip-shaped or tubular structure, and at least one surface of the drainage element is arrayed with a plurality of conical microstructures inclined in the same direction; the drainage element material includes continuous hydrophilic and hydrophobic microregions, wherein the hydrophilic gel skeleton presents an ordered strip shape, and the hydrophobic microregions are attached to the hydrophilic strips and distributed in an ordered strip shape. Wherein, the hydrophilic phase is a gel skeleton formed by the polymerization of hydrophilic chain polymers, and the hydrophobic micro-regions are micro-regions formed by submicron-sized hydrophobic phase particles distributed on the gel skeleton; The water content of the drainage component when it is fully swollen in water is 31%-51%, the tensile strength is not less than 2.1 MPa, and the elongation at break is 350%-560%.

[0028] In this application, the hydrophobic microregions are formed by hydrophobic particles with a diameter of less than 3 μm. The diameter of each hydrophobic microregion is also less than 3 μm, and the spacing between adjacent hydrophobic microregions in the band-like direction is less than 10 μm; in the direction perpendicular to the band, the spacing between adjacent hydrophobic microregions is no higher than 10 μm. The diameter of the hydrophobic particles constituting the hydrophobic microregions should not be too high, and the formed hydrophobic microregions should not be too large. This is because excessively large-diameter hydrophobic microregions are larger than the width of the gel skeleton and cannot adhere uniformly to the gel skeleton, leading to a decrease in the strength and stability of the material. Furthermore, the spacing between the hydrophobic microregions in the band-like direction should not be too high, because excessively high spacing represents an excessively high continuous area of ​​the hydrophilic phase containing water. During the dehydration-swelling toughening process, the volume change is too drastic, resulting in excessive loss of surface microstructure.

[0029] In this application, the hydrophobic microregions are formed by several hydrophobic microregions attached to a gel skeleton with a certain orderly distribution, giving it a visual band-like effect, rather than a long strip-like structure of hydrophobic phase. The spacing between adjacent hydrophobic microregions is preferably controlled within the range of 1μm to 5μm, which prevents the volume change during the dehydration, swelling, and toughening process of the gel material from being too drastic, resulting in a significant improvement in mechanical properties after toughening.

[0030] The mass ratio of the hydrophilic phase to the hydrophobic phase is 2:1 to 1:3, preferably 1:1 to 1:3, and more preferably 1:1 to 1:2. In this application, the mass ratio of the hydrophilic phase to the hydrophobic phase should not be too high or too low. An excessively high mass ratio will lead to excessive loss of surface microstructures during the toughening process, while an excessively low mass ratio will result in reduced material strength or even prevent it from being formed.

[0031] The hydrophobic phase is a hydrophobic biocompatible polymer that exists in a solid state below 40°C. This allows it to not only have good biocompatibility but also to form in a solid state within the hydrophilic phase. During the curing process of the hydrophilic phase, it does not need to undergo curing but is simply fixed by the cured hydrophilic phase, forming a stable embedded microstructure.

[0032] The hydrophilic phase is selected from one or more of polyvinyl alcohol, sodium alginate, hyaluronic acid, and gelatin; the hydrophobic phase is selected from one or more of medical-grade anhydrous lanolin, food-grade beeswax, medical silicone gel, polyolefin elastomer, plant-based glyceryl stearate, petrolatum, long-chain alkanes, and solid oils. It should be noted that in this application, the hydrophilic phase is defined as excluding water in the drainage element, drainage material, or reaction system, and is only a hydrophilic polymer; while the aqueous phase is defined as a phase including both hydrophilic polymer and water. In this application, the hydrophobic phase is defined the same as the oil phase, which is hydrophobic polymer particles.

[0033] In some embodiments, the drainage element does not include either an initiator or a catalyst, in order to avoid the initiator and catalyst remaining as free small molecules inside the material after synthesis, entering the wound with the water phase during the drainage process, and causing biotoxicity.

[0034] In some embodiments, the drainage element does not contain water-soluble compounds with a molecular weight not exceeding 500.

[0035] In this application, the hydrophilic phase can be cured by physical crosslinking or ionic crosslinking. In this application, the curing and crosslinking of the hydrophilic phase is not crosslinking by forming strong chemical bonds such as covalent bonds, but by using relatively weak bonds such as hydrogen bonds and ionic bonds. This can provide the material with strong and tough mechanical properties without the need to introduce additives such as initiators and catalysts, thus avoiding the addition of free small chemical molecules in the bulk phase that could cause biotoxicity.

[0036] In this application, the cross-section of the drainage material is smooth and flat when observed under an electron microscope at 2000x magnification, and no pore structure is observed. That is, the drainage material provided in this application does not contain pores with a diameter greater than 1μm.

[0037] In this application, the drainage element material is obtained by polymerizing a prepolymer liquid comprising the following components: With the mass fraction of the prepolymer liquid being 100%, the mass fraction of the hydrophobic phase in the prepolymer liquid is 5%~25%; the mass fraction of the aqueous phase is 75~95%; and the mass percentage of the hydrophilic chain polymer material in the aqueous phase of the prepolymer liquid is not higher than 20%.

[0038] The conical microstructure is obtained by in-situ polymerization of the flow guide material on a template with a corresponding microstructure. The loss rate during the flow guide molding, demolding and toughening process is no higher than 4.2%.

[0039] The conical microstructure has a length of 200 μm to 500 μm in the direction of the tube axis of the drainage device, and a length of 120 μm to 300 μm in the direction perpendicular to the tube axis.

[0040] The conical microstructure is obtained by in-situ polymerization of the flow guide material on a template with a corresponding microstructure. The loss rate during the flow guide molding, demolding and toughening process is no higher than 4.2%.

[0041] To facilitate better implementation of this application by those skilled in the art, this application also provides a method for preparing a flexible, strong, and highly biocompatible drainage component. The method involves casting an oil-water emulsion prepolymer onto a template, followed by solidification through physical cross-linking processes such as freezing and melting. After demolding, a drying-swelling process is performed to achieve secondary toughening of the material. The preparation process requires no cross-linking agents, and no polymerization initiated by ultraviolet light or high temperatures. The resulting gel tube is easy to demold and maintains its inner wall microstructure while possessing high flexibility. Furthermore, the gel tube prepared by this application uses an oil-water gel. The addition of the aqueous polymer phase provides material molding and stability to the oil-water emulsion, while the addition of the hydrophobic phase improves the volume change rate during the secondary toughening process of the gel tube, reduces microstructure deformation, and maintains the microstructure morphology.

[0042] The wound drainage device is prepared by a method including the following steps: A prepolymer solution is provided, the prepolymer solution comprising a hydrophobic phase and an aqueous phase; Emulsify the prepolymer to obtain an emulsion; An emulsion is applied to a template, which is tubular and has several conical microgrooves arranged in an array on its inner wall, extending in the same direction. A template coated with emulsion was frozen and thawed to solidify the emulsion. The template was then peeled off to obtain a primary gel material with several conical microstructures arrayed on its surface. After the primary gel material is dehydrated in the atmosphere, it is swollen with an aqueous fluid to obtain a tubular wound drainage device with conical microstructures on the inner wall.

[0043] It should be noted that the hydrophobic phase is a phase in the system that is not easily soluble in water, such as monomers, oligomers, and polymers of hydrophobic compounds. The aqueous phase is a phase in the system that is well compatible with water, such as oligomers and polymers of chain-like hydrophilic compounds. In this application, the hydrophobic phase is an oligomer of a hydrophobic gel; the aqueous phase is a solution formed by water and the oligomer of the hydrophilic gel.

[0044] It should also be noted that "melting" in this application does not refer to the material being melted into a fluid state, but rather to the state in which the aqueous phase of the oil-hydrogel material melts from ice to water after it has left its frozen state.

[0045] The hydrophobic phase is introduced into the aqueous phase and then mixed to obtain a prepolymer solution.

[0046] In the prepolymer solution, the mass ratio of the aqueous phase to the hydrophobic phase is (2:1) to (1:3), and the mass fraction of the hydrophilic chain polymer in the aqueous phase is 5% to 17.5%. Preferably, the mass ratio of the aqueous phase to the hydrophobic phase is (1:1) to (1:3), and the mass fraction of the oligomers of the hydrophilic gel in the aqueous phase is 7.5% to 15%. More preferably, the mass fraction of the oligomers of the hydrophilic gel in the aqueous phase is 10% to 12.5%.

[0047] The concentration of the aqueous phase polymer in the prepolymer should not be too high or too low. This is because an excessively high concentration of chain-like hydrophilic polymers will result in high viscosity and poor flowability of the oil-water emulsion, making it difficult to coat the template and thus preventing replication. Conversely, an excessively low concentration of chain-like hydrophilic polymers will prevent the gel from curing. Furthermore, the mass percentage of the hydrophobic phase in the prepolymer should not be too high or too low. An excessively high percentage of hydrophobic phase will prevent the gel from curing, while an excessively low percentage of hydrophobic phase will result in insufficient strength of the drainage element, a large volume change rate before and after swelling, and a high microstructure deformation rate.

[0048] The hydrophilic chain polymer compound has a molecular weight of 10,000-100,000. The hydrophobic phase is a hydrophobic polymer that is solid below 40°C. The mass ratio of the hydrophilic polymer to the hydrophobic phase is 2:1 to 1:3. Furthermore, since this application is intended for use in wounds, both the oleogel and the chain hydrophilic polymer material selected are biocompatible gel materials. In addition, the applicant has found that the hydrophobic gel material and the chain hydrophilic polymer material selected in this application are specific materials. The oleogel is preferably a mixture of one or more of petrolatum, PDMS (polydimethylsiloxane), and silicone oil; while the chain hydrophilic polymer material is preferably a mixture of one or more of polyvinyl alcohol, sodium alginate, hyaluronic acid, and gelatin. The applicant has found that the above-mentioned oleogel and chain hydrophilic polymer material can be cured without crosslinking agents and ultraviolet light initiation. The emulsion formed by the emulsification of the two can be cured during the freeze-thaw process, and the volume change rate after curing and swelling is small. In addition, it has good demolding performance, and the tensile strength of the resulting drainage part is also excellent.

[0049] More preferably, the hydrophilic gel is polyvinyl alcohol, and the oleogel is petrolatum.

[0050] In some embodiments, the emulsification temperature is 60°C-80°C, which can reduce the viscosity of the polymer solution and liquefy hydrophobic substances, or a hydrophobic monomer prepolymer can be used, followed by polymerization after emulsification. Hydrophilic polymers not only provide strength as a skeletal support during gel formation but also act as surfactants to stabilize the emulsion during emulsification. The emulsification method can be ultrasonic emulsification or existing emulsification methods such as stirring emulsification.

[0051] In some embodiments, the freezing and thawing process can be repeated multiple times to enhance the initial strength of the material, preferably repeated 2 to 3 times.

[0052] Specifically, the freezing and thawing process includes: Place the template coated with emulsion in an environment of 0-80℃ for 4-24 hours to freeze, and then place it in an environment of 20-30℃ for 2-24 hours to thaw.

[0053] Preferably, the freezing temperature is -20°C and the freezing time is 12 hours; the thawing temperature is 25°C and the thawing time is 4 hours.

[0054] When the freezing and melting process involves multiple freezing and melting processes, the freezing time in the first freezing and melting process shall not be less than 4 hours to ensure the solidification degree of the emulsion and to maintain its morphology as much as possible during subsequent processing.

[0055] After the gel tube has solidified and formed, it can be peeled off from the template, at which point an array of conical microstructures has formed on the inner wall of the gel tube. After the microstructures are formed on the gel tube, the drainage tube undergoes a secondary toughening treatment.

[0056] In this application, the secondary toughening treatment is a swelling toughening process, specifically involving: placing the gel tube in an atmospheric environment to completely dehydrate it, then completely immersing it in an aqueous fluid to induce swelling. The swelling treatment time is 12-24 hours, and the swelling treatment temperature is 25°C; the aqueous fluid is deionized water.

[0057] The swelling process can further increase the tensile strength of the gel tube, thereby achieving better flexibility.

[0058] It should be noted that during the dehydration process, the volume shrinkage rate of the primary gel material is no higher than 80%; during the swelling treatment, the volume expansion rate of the primary gel material is no more than 100%, so that the deformation rate of the formed microstructure is smaller.

[0059] The volume shrinkage rate and swelling volume change rate during the dehydration process are (initial material volume - volume after complete dehydration) / initial material volume. The volume change rate of the wound drainage component before and after soaking in deionized water for 1 hour is also described. The volume expansion rate during the reswelling process is (re-swelling volume of material - dehydrated volume of material) / dehydrated volume of material.

[0060] Secondly, this application also provides a drainage device, which includes a flexible, strong, and highly biocompatible drainage device prepared by the method for preparing the flexible, strong, and highly biocompatible drainage device described in the first aspect or the flexible, strong, and highly biocompatible drainage device described in the second aspect.

[0061] The technical solution of the present invention will be clearly and completely described below with reference to the embodiments. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0062] Example 1 This embodiment provides a method for preparing a flexible, strong, and highly biocompatible drainage device, which specifically includes the following steps: S1: Preparation of prepolymer solution Take 5g of PVA (polyvinyl alcohol) with a molecular weight of 50,000 and a degree of alcoholysis of 98% and dissolve it in 45g of deionized water to obtain a PVA aqueous solution; take 5g of petrolatum (purchased from Haisheng Hainuo Company, model: white petrolatum, melting point: 40-60℃, weight average molecular weight: 209.3) and add it to the PVA aqueous solution to obtain a prepolymer solution; S2: Preparing the emulsion The prepolymer solution was sonicated using a cell disruptor with a total power of 750W, 80% power, a temperature of 80℃, a frequency of 25KHz, a single sonication time of 6s (2s on, 2s off), and a total sonication time of 3min to obtain the emulsion. S3: Preparation of primary gel materials Templates are provided, comprising: square grooves with a 45° angled micro-cones arrayed on the surface, the grooves being 1.0-3.0 mm deep, 30 mm-200 mm long, and 10 mm-200 mm wide, with the micro-cones approximately 0.3 mm high; or cylinders with a 45° angled micro-cones arrayed in a ring on the surface, the outer perimeter being isolated by hollow cylinders of the same height, the diameter of the cylinders being 1 mm-5 mm, the inner diameter of the hollow cylinders being 3 mm-10 mm, the outer diameter being 5 mm-12 mm, and the inner diameter being... The emulsion is at least 2 mm larger than the diameter of the cylinder, with a 2 mm difference between the inner and outer diameters. It is applied to a template, ensuring the emulsion completely covers the square grooves or completely fills the tubular space separating the hollow cylinder and the cylinder with the array of microstructures. The template is then placed in a -20°C freezer for 12 hours, removed, and allowed to thaw at 25°C for 2 hours. This process is repeated, resulting in a primary gel material with an array of conical microgrooves on its surface. S4: Prepare wound drainage devices The primary gel material was completely dehydrated at 25°C in an atmospheric environment. The dehydrated gel material was then placed in deionized water at 25°C, ensuring that the deionized water completely submerged the gel material, and soaked for 12 hours to obtain a wound drainage device.

[0063] Example 2 Compared to Example 1, the PVA in the PVA aqueous solution of the prepolymer used in step S1 has a mass fraction of 5%, while the remaining steps are the same as in Example 1, resulting in a wound drainage device.

[0064] Example 3 Compared to Example 1, the PVA mass fraction in the PVA aqueous solution of the prepolymer used in step S1 is 7.5%, and the remaining steps are the same as in Example 1, resulting in a wound drainage device.

[0065] Example 4 Compared to Example 1, the PVA mass fraction in the PVA aqueous solution of the prepolymer used in step S1 is 12.5%, and the remaining steps are the same as in Example 1, resulting in a wound drainage device.

[0066] Example 5 Compared to Example 1, the PVA mass fraction in the PVA aqueous solution of the prepolymer used in step S1 is 15%, and the remaining steps are the same as in Example 1, resulting in a wound drainage device.

[0067] Example 6 Compared to Example 1, the amount of hydrophobic phase in the prepolymer solution used in this embodiment is 6.25g in step S1, and the remaining steps are the same as in Example 1, resulting in a wound drainage device.

[0068] Example 7 Compared to Example 1, the amount of hydrophobic phase in the prepolymer solution used in this embodiment is 8.3g in step S1, and the remaining steps are the same as in Example 1, resulting in a wound drainage device.

[0069] Example 8 Compared to Example 1, the amount of hydrophobic phase in the prepolymer solution used in this embodiment is 12.5g in step S1, and the remaining steps are the same as in Example 1, resulting in a wound drainage device.

[0070] Example 9 Compared to Example 1, in this embodiment, the aqueous phase of the prepolymer solution used in step S1 is PVA aqueous solution, the hydrophobic phase is PDMS, and the amount of hydrophobic phase is 10.0g. The remaining steps are the same as in Example 1, and a wound drainage device is obtained.

[0071] Example 10 Compared to Example 1, in this embodiment, the hydrophobic phase in the prepolymer solution used in step S1 is replaced with PDMS prepolymer solution, and the amount of hydrophobic phase is 12.5g. The remaining steps are the same as in Example 1, and a wound drainage device is obtained.

[0072] Example 11 Compared to Example 1, in this embodiment, the hydrophobic phase in the prepolymer solution used in step S1 is replaced with PDMS prepolymer solution, and the amount of hydrophobic phase is 16.7g. The remaining steps are the same as in Example 1, and a wound drainage device is obtained.

[0073] Example 12 Compared to Example 8, step S4 in this embodiment is repeated twice, while the remaining steps are the same as in Example 8, resulting in a wound drainage device.

[0074] Comparative Example 1 Compared to Example 1, only 5g of PVA (polyvinyl alcohol) with a weight average molecular weight of 1700 was dissolved in 45mL of deionized water to obtain an aqueous PVA solution. Step S4 was omitted, and the remaining steps were the same as in Example 1 to obtain a wound drainage device.

[0075] Comparative Example 2 Compared to Example 1, step S4 is omitted, while the remaining steps are the same as in Example 1, resulting in a wound drainage device.

[0076] Comparative Example 3 Compared to Example 1, in step S1 of this comparative example, only 5g of PVA (polyvinyl alcohol) with a weight-average molecular weight of 1700 was dissolved in 45mL of deionized water to obtain a PVA aqueous solution; the remaining steps were the same as in Example 1 to obtain the comparative wound drainage device 1.

[0077] Comparative Example 4 Compared to Example 1, in step S1 of this comparative example, only pure petroleum jelly was used; the remaining steps were the same as in Example 1, resulting in a comparative wound drainage device.

[0078] Comparative Example 5 Compared to Example 1, in step S1 of this comparative example, only pure PDMS prepolymer solution was used; the remaining steps were the same as in Example 1, resulting in a comparative wound drainage device.

[0079] Comparative Example 6 Compared to Example 1, the PVA mass fraction in the PVA aqueous solution of the prepolymer used in this comparative example is 2.5%, and the remaining steps are the same as in Example 1, to obtain a wound drainage device.

[0080] Comparative Example 7 Compared to Example 1, the PVA in the PVA aqueous solution of the prepolymer used in this comparative example has a mass fraction of 20%, and the remaining steps are the same as in Example 1, resulting in a wound drainage device.

[0081] Comparative Example 8 Compared to Example 1, the amount of hydrophobic phase in the prepolymer used in step S1 is 25.0g, and the remaining steps are the same as in Example 1, resulting in a wound drainage device.

[0082] Comparative Example 9 Compared to Example 1, in this embodiment, the hydrophobic phase in the prepolymer solution used in step S1 is replaced with PDMS prepolymer solution, and the amount of hydrophobic phase is 25.0g. The remaining steps are the same as in Example 1, and a wound drainage device is obtained.

[0083] Comparative Example 10 Compared to Example 1, this comparative example uses AM (acrylamide) monomer in the aqueous phase at a mass fraction of 10%, and step S3 is replaced with photopolymerization crosslinking for 30 minutes at a wavelength of 405 nm. The remaining steps are the same as in Example 1, resulting in a comparative drainage device.

[0084] Comparative Example 11 Compared to Example 1, the aqueous phase of the prepolymer solution used in step S1 is AM (acrylamide) aqueous solution, and the hydrophobic phase is LMA (lauryl methacrylate). Step S3 is changed to photopolymerization crosslinking for 30 min at a wavelength of 405 nm. The remaining steps are the same as in Example 1, and a wound drainage device is obtained.

[0085] Comparative Example 12 Compared to Example 1, the amount of hydrophobic phase in the prepolymer used in step S1 is 50.0g, and the remaining steps are the same as in Example 1, resulting in a wound drainage device.

[0086] The drainage tubes obtained in Examples 1-12 and Comparative Examples 1-11 were tested for microstructure deformation rate, tensile strength, elongation at break, elastic modulus, drying volume shrinkage rate, swelling volume expansion rate, and water content. The specific testing methods are as follows: (1) Microstructure deformation rate An emulsion was applied to a 3D template with an array of microstructured protrusions. After a freeze-thaw cycle, the gel was exfoliated from the template to obtain a primary gel material with a microstructured surface. The primary gel material was toughened by a dry-swell cycle, and the surface microstructure morphology was characterized using a macro camera. The total number of microgroove structures N0 and the number of distorted microgroove structures N1 were recorded.

[0087] Microstructure deformation rate = N1 / N0*100.

[0088] (2) Characterization of the morphology of the hydrophilic and hydrophobic phases on the surface of the drainage component material.

[0089] The final material of the drainage component was frozen with liquid nitrogen and then freeze-dried to completely dehydrate it while preserving the surface microstructure to the greatest extent possible. The material was fabricated into a 5mm*5mm*2mm block, fixed to the sample stage with conductive adhesive, and then sputter-coated with gold to increase surface conductivity. The surface morphology was observed under a scanning electron microscope, and the diameter and number of hydrophobic microregions in the image at 5000x magnification were counted. The average diameter and spacing of the hydrophobic microregions were calculated.

[0090] The hydrophilic phase of the drainage material was stained with 0.01% Rhodamine 123, and the hydrophobic phase was stained with 0.02% Perylene Red. Rhodamine 123 exhibited green fluorescence under 488 nm excitation, while Perylene Red fluoresced red under 561 nm excitation. Observation of the material under a confocal fluorescence microscope revealed a clear continuous green hydrophilic phase and banded hydrophobic microregions. The spacing between the hydrophobic microregion bands in the 100x image was statistically analyzed, and the average spacing of the hydrophobic microregion bands was calculated.

[0091] (3) Tensile strength, elongation at break and modulus of elasticity.

[0092] Fix both ends of the final material of the drainage component onto the clamps of the universal testing machine. Tighten the clamps and adjust the distance between the two ends of the material until the material is under stress. Record the distance *l* between the two ends of the clamp at this point, and measure the width *w* and thickness *th* of the material. Set the force collected by the force sensor to zero, fix the lower clamp, and move the upper clamp at a speed of 5 mm / min. Record the real-time reading *F* of the force sensor and the real-time movement distance *d* of the clamp. Continue until the material fractures, and record the reading *F* of the force sensor at this point. end The distance d that the clamp moves end .

[0093] Tensile strength = F end / w*th Elongation at break = d end / l*100 Elastic modulus: Plot a curve with the force F when the elongation of the material is between 5% and 10% as the vertical axis and the elongation as the horizontal axis. Use fitting to calculate the slope of the curve. The value of the slope is the elastic modulus of the material.

[0094] (4) Drying volume shrinkage rate and swelling volume growth rate Measure the length l0, width w0, and thickness th0 of the primary gel material, and calculate the volume V0 = l0 * w0 * th0. After the gel is completely dried in air, measure the length l1, width w1, and thickness th1 of the dried gel material, and calculate the volume V1 = l1 * w1 * th1. Place the dried gel in sufficient deionized water and allow it to swell for 24 hours. Then measure the length l2, width w2, and thickness th2 of the gel material, and calculate the volume V2 = l2 * w2 * th2.

[0095] Drying volume shrinkage rate = V1 / V0 * 100 Swelling volume growth rate = (V2 - V1) / V1 * 100 The test results are shown in Table 1.

[0096] Table 1

[0097] from Figure 3 As can be seen, in the drainage element provided in this application, the hydrophobic phase is dispersed in the hydrophilic phase gel skeleton in a particulate state, forming several hydrophobic phase microregions dispersed in the hydrophilic phase gel skeleton. From Table 1, and... Figures 5-8 It can be seen that the drainage material prepared in this application can increase the Young's modulus by up to 356 times and the tensile strength by up to 53 times compared to pure polyvinyl alcohol hydrogel, and has an elongation at break that is similar to or even better than that of pure polydimethoxysilane (PDMS) gel; compared to pure polydimethoxysilane (PDMS) gel, the Young's modulus can be increased by up to 1.7 times, the tensile strength by up to 3.0 times, and the elongation at break by up to 3.3 times; compared to the prepared primary gel material, the secondary toughening process can increase the Young's modulus by 24 times, the tensile strength by 14 times, and the elongation at break by 1.4 times. Figure 4 , Figure 9 , Figure 10 It can be seen that, compared with the secondary toughening process using pure polyvinyl alcohol, the drying volume shrinkage rate of this material can be reduced by up to 40%, and the swelling volume growth rate can be reduced by up to 280%, thereby reducing the microstructure loss rate to 0.3%. The mechanical properties of the material can be controlled by adjusting the mass fraction of the aqueous polyvinyl alcohol and the mass ratio of the aqueous and hydrophobic phases. Furthermore, by adjusting the mass ratio of the aqueous and hydrophobic phases, the drying volume shrinkage rate and swelling volume growth rate during the secondary toughening process can be improved, thus improving the microstructure deformation rate of the flexible wound drainage component during its fabrication.

[0098] To investigate the superior properties of the drainage tube obtained in this application, such as microstructure deformation rate and tensile strength, the applicant also observed the bulk phases of the gel materials obtained in Example 1, Comparative Example 1, and Comparative Example 2 under an electron microscope. The SEM images are shown below. Figure 2As shown, from Figure 2 As can be seen, no hydrogel channels can be observed in the drainage material provided in this application at 2000x magnification, indicating that its molecules are tightly bound together and there are almost no pores larger than 1μm, resulting in higher mechanical strength.

[0099] In addition, to study the biocompatibility of the drainage tubes provided in this application, the applicant extracted the drainage tubes obtained in Example 1, Comparative Example 1, and Comparative Example 2 into DEME medium for 24 h, cultured mouse fibroblast L929 cells in the extract, and cultured them at 37°C for 24 and 48 h. The fluorescence intensity of live cells after CCK-8 staining and the distribution of live and dead cells were detected, and the results are as follows. Figure 11 , Figure 12 As shown. From Figure 11 , Figure 12 It can be seen that the drainage tube provided in this application has good biocompatibility.

[0100] In summary, the method for preparing the wound drainage tube provided in this application can produce a wound drainage tube with low microstructure deformation rate and high tensile strength, avoiding the technical problem in the prior art where the microstructure of the drainage tube using Laplace pressure is easily deformed during molding, thus affecting its drainage effect.

[0101] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of this application, and are not intended to limit them. Although this application has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features therein. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of this application.

Claims

1. A flexible, strong, and highly biocompatible drainage device, characterized in that: The drainage element is a strip-shaped or tubular structure, and at least one surface of the drainage element is arrayed with a plurality of conical microstructures inclined in the same direction. The drainage component includes a continuous hydrophilic phase and ordered hydrophobic microregions therein, wherein the hydrophilic phase gel skeleton presents an ordered strip shape, and the hydrophobic microregions are attached to the hydrophilic strips and are distributed in an ordered strip shape; the hydrophilic phase is a gel skeleton polymerized from hydrophilic chain polymers, and the hydrophobic microregions are microregions formed by submicron-sized hydrophobic phase particles distributed on the gel skeleton. The drainage component, when fully swollen in water, has a water content of 31%-51%, a tensile strength of not less than 2.1 MPa, and an elongation at break of 350%-560%; the deformation rate of the conical microstructure is 0.6-4.2%. The drainage device is prepared by a method including the following steps: A prepolymer solution is provided, the prepolymer solution comprising a hydrophobic phase and an aqueous phase; Emulsify the prepolymer to obtain an emulsion; An emulsion is applied to a template, which is tubular and has several conical microgrooves arranged in an array on its inner wall, extending in the same direction. A template coated with emulsion was frozen and thawed to solidify the emulsion. The template was then peeled off to obtain a primary gel material with several conical microstructures arrayed on its surface. After the primary gel material is dehydrated in the atmosphere, it is swollen with an aqueous fluid to obtain a tubular drainage device with conical microstructures on its inner wall.

2. The flexible, strong, and highly biocompatible drainage device according to claim 1, characterized in that, The diameter of the hydrophobic microregion is less than 3 μm, and the interval between adjacent hydrophobic microregions in the band-shaped direction is less than 10 μm; in the direction perpendicular to the band, the interval between adjacent hydrophobic microregions is no higher than 10 μm.

3. The flexible, strong, and highly biocompatible drainage device according to claim 1, characterized in that, In the fully swollen draining element, the mass fraction of the hydrophilic phase is 5%-40%, the mass fraction of the hydrophobic phase is 20%-45%, and the mass ratio of the hydrophilic phase to the hydrophobic phase is 2:1 to 1:

3.

4. The flexible, strong, and highly biocompatible drainage device according to claim 1, characterized in that, The hydrophilic phase is selected from one or more of polyvinyl alcohol, sodium alginate, hyaluronic acid, and gelatin; the hydrophobic phase is selected from one or more of medical-grade anhydrous lanolin, medical silicone gel, plant-based glyceryl stearate, and petrolatum.

5. The flexible, strong, and highly biocompatible drainage device according to claim 1, characterized in that, When the hydrophilic phase is a non-amphiphilic polymer, the material of the drainage element also includes a biocompatible surfactant, which meets the following requirements: HLB value of 8.0-14.0; cytotoxicity level of no more than grade 1 according to ISO 10993-5:2009; and hemolysis rate of less than 5% according to ISO 10993-4:2017.

6. The flexible, strong, and highly biocompatible drainage device according to claim 5, characterized in that, The surfactant is selected from one or more of the following: lecithin, phosphatidylcholine, phosphatidylethanolamine, Tween 80, Tween 20, gelatin derivatives, and albumin.

7. The flexible, strong, and highly biocompatible drainage device according to claim 1, characterized in that, The drainage element does not include any of the initiators or catalysts.

8. The flexible, strong, and highly biocompatible drainage device according to claim 1, characterized in that, The hydrophilic phase is cured through physical crosslinking or ionic crosslinking.

9. The flexible, strong, and highly biocompatible drainage device according to claim 1, characterized in that, When the cross-section of the drainage component is observed under an electron microscope at a magnification of 2000x, the surface is smooth and flat, and no pore structure is visible.

10. The flexible, strong, and highly biocompatible drainage device according to claim 1, characterized in that, The material of the drainage element is obtained by polymerizing a prepolymer containing the following components: With the mass fraction of the prepolymer liquid being 100%, the mass fraction of the hydrophobic phase in the prepolymer liquid is 5%~25%; the mass fraction of the aqueous phase is 75~95%; and the mass percentage of the hydrophilic chain polymer material in the aqueous phase of the prepolymer liquid is not higher than 20%.

11. The flexible, strong, and highly biocompatible drainage device according to claim 1, characterized in that, The conical microstructure is obtained by in-situ polymerization of the material of the flow guide on a template with a corresponding microstructure. The loss rate during demolding and toughening of the flow guide is no higher than 4.2%.

12. The flexible, strong, and highly biocompatible drainage device according to claim 1, characterized in that, The conical microstructure has a length of 200 μm to 500 μm in the direction of the tube axis of the drainage device, and a length of 120 μm to 300 μm in the direction perpendicular to the tube axis.

13. A drainage device, characterized in that, Includes the flexible, strong, and highly biocompatible drainage device as described in any one of claims 1 to 12.

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