Absorbable auxiliary material and preparation method thereof

Abstract

The invention discloses an absorbable auxiliary material and a preparation method thereof. The preparation method comprises the following steps: mixing a high polymer material serving as a base material with an inorganic material to form a composite material; putting the composite material into a dissolving agent, and mixing to obtain a uniformly dispersed mixed solution; adding nano-particles into the mixed solution to obtain a composite solution containing the nano-particles; spinning the composite solution into a nanofiber net-shaped structure through electrostatic spinning equipment, putting the nanofiber net-shaped structure into a crosslinking furnace, carrying out crosslinking curing treatment on the nanofiber net-shaped structure in a nitrogen atmosphere, and soaking the nanofiber net-shaped structure in an acid solution to carry out hydrolysis reaction, so as to obtain a nanofiber net-shaped structure; the absorbable auxiliary material is prepared by covering a biocompatible coating on the surface of a nano-fiber net-shaped composite material subjected to hydrolysis reaction through a chemical vapor deposition technology and then carrying out cleaning and vacuum drying treatment. By optimizing raw material selection, improving the preparation process and finely controlling the material structure, the performance of the absorbable auxiliary material is remarkably improved.

Description

Technical Field

[0001] The present application relates to the technical field of absorbable auxiliary materials, and in particular to an absorbable auxiliary material and a preparation method thereof. Background Art

[0002] With the widespread application of biomedical materials, especially in the field of wound repair and tissue engineering, absorbable excipients (such as degradable dressings, implants, etc.) have become an important treatment method. Existing absorbable excipients are in the form of a composite of polymer materials and inorganic substances to achieve ideal biodegradability and mechanical properties.

[0003] However, the absorbable excipients in the prior art have some limitations in many aspects, especially in terms of uniformity, degradation rate and biocompatibility of the material, and still cannot meet certain clinical needs. Specifically, the prior art is to compound polymer materials with inorganic fillers by simple physical mixing or melting method. Although this method can improve the mechanical properties and biodegradability of the material to a certain extent, due to the poor compatibility between polymer materials and inorganic substances, the performance of the composite material is often unstable, and physical properties are prone to decline during use. In addition, since most polymer materials and inorganic materials are combined in a rough manner, the microstructure of the composite material is uneven, which affects the overall performance of the material, especially in terms of absorbability, controllability of degradation rate and biocompatibility. Therefore, the existing composite excipients often have problems such as unstable performance and unadjustable degradation rate in practical applications, which limits their promotion and application in clinical practice. Summary of the invention

[0004] The purpose of the present application is to provide an absorbable auxiliary material and a preparation method thereof, so as to solve the technical problems of unstable material properties and difficult control in the preparation process of the existing absorbable auxiliary materials.

[0005] To achieve this goal, this application adopts the following technical solutions: A method for preparing an absorbable auxiliary material, comprising: Mixing a polymer material as a base material with an inorganic material, and heating the mixture to form a composite material; The composite material is placed in a solvent for mixing, and dispersed evenly by ultrasonic vibration to obtain a uniformly dispersed mixed solution; Adding nanoparticles to the mixed solution to obtain a composite solution containing nanoparticles, wherein the surfaces of the nanoparticles are modified by a surface modifier; The composite solution is spun into a nanofiber mesh structure by an electrostatic spinning device, the nanofiber mesh structure is placed in a cross-linking furnace, and the nanofiber mesh structure is cross-linked and cured under a nitrogen atmosphere to obtain a nanofiber mesh composite material; The nanofiber mesh composite material is immersed in an acidic solution to perform a hydrolysis reaction, and a biocompatible coating is coated on the surface of the nanofiber mesh composite material after the hydrolysis reaction by chemical vapor deposition technology; The nanofiber mesh composite material is placed in an organic solvent for washing to obtain a pure composite material, and the pure composite material is subjected to vacuum drying to prepare an absorbable auxiliary material.

[0006] Furthermore, the polymer material is at least one of gelatin, chitosan or hyaluronic acid, and the inorganic material is at least one of hydroxyapatite or nano-silicon. Calculated by weight percentage, in the composite material, the polymer material accounts for 70-90%, and the inorganic material accounts for 10-30%.

[0007] Furthermore, the solvent is at least one of chloroform, dichloromethane or ethanol. Calculated by mass percentage, in the mixed solution, the solvent accounts for 5-15%, and the rest is the composite material.

[0008] Furthermore, the nanoparticles are at least one of zinc oxide, nano-silicon dioxide or nano-cellulose, and the surface modifier is aminosilane.

[0009] Furthermore, the step of placing the composite material into a solvent for mixing, and dispersing it uniformly by ultrasonic vibration to obtain a uniformly dispersed mixed solution comprises: Cutting the composite material into a predetermined size range to obtain composite material particles, wherein the size range is 50-500 microns; The composite material particles and the dissolving agent are mixed and soaked for 1 to 2 hours to obtain a preliminary soaking mixed solution, and the soaking mixed solution is placed in an ultrasonic oscillation device, the ultrasonic oscillation frequency is set to 20 to 40 kHz, the oscillation power is set to 150 to 300 W, and the oscillation time is controlled to be 15 to 30 minutes to obtain a preliminary dissolved solution; The preliminary dissolved solution is heated to a temperature range of 40-60° C. and kept at a constant temperature for 20-60 minutes to obtain a pre-treated uniformly dispersed solution; Performing a particle size distribution test on the uniformly dispersed solution based on a dynamic light scattering method to determine whether the particle size dispersion in the uniformly dispersed solution is less than 10%; If both are positive, a uniformly dispersed mixed solution is obtained; if both are negative, the ultrasonic oscillation time and power are adjusted until the particle size dispersion in the uniformly dispersed solution is less than 10%.

[0010] Furthermore, the step of adding nanoparticles to the mixed solution to obtain a composite solution containing nanoparticles, wherein the surface of the nanoparticles is modified by using a surface modifier, comprises: The nanoparticles are immersed in a solution containing ethanol and deionized water for ultrasonic cleaning to remove pollutants and impurities that may exist on the surface of the particles, thereby obtaining nanoparticles with preliminarily cleaned surfaces; Dispersing the washed nanoparticles into an acetonitrile solution, adding the surface modifier, the modification time is 2 to 4 hours, and stirring so that the modifier is uniformly adsorbed on the surface of the nanoparticles to obtain surface-modified nanoparticles; The surface-modified nanoparticles are added to the mixed solution, and the mixed solution is stirred using a magnetic stirrer for 1 to 2 hours to obtain a composite solution containing surface-modified nanoparticles, wherein the nanoparticles account for 1% to 5% by mass, and the rest is the mixed solution.

[0011] Furthermore, the step of spinning the composite solution into a nanofiber mesh structure through an electrospinning device, placing the nanofiber mesh structure in a cross-linking furnace, and cross-linking and curing the nanofiber mesh structure under a nitrogen atmosphere to obtain a nanofiber mesh composite material comprises: The composite solution is sprayed through an electrospinning device, the spray voltage of the electrospinning device is controlled to be 15-30 kV, the electrode spacing is 10-20 cm, and the spray flow rate is 0.1-0.5 mL / h, and the composite solution is spun to obtain a pre-spun nanofiber mesh structure; The nanofiber network structure is placed in an oven at a temperature of 50-80° C. for heat treatment for 2-4 hours, and the heat-treated nanofiber network structure is immersed in a crosslinking agent solution for 30-60 minutes, so that the crosslinking agent reacts with the functional groups on the surface of the nanofibers to obtain a pre-crosslinked nanofiber network structure, wherein the crosslinking agent solution is polyisocyanate or polyol, and the concentration of the crosslinking agent is 5-20 wt% calculated by mass ratio percentage; The pre-crosslinked nanofiber mesh structure is placed in a crosslinking furnace and cured in a nitrogen atmosphere. The furnace temperature is controlled at 120-180° C. and the curing time is 2-4 hours to obtain a crosslinked and cured nanofiber mesh composite material.

[0012] Furthermore, after the step of obtaining the cross-linked and cured nanofiber mesh composite material, the process further comprises: The nanofiber mesh composite material is cleaned in an anhydrous ethanol solution using an ultrasonic cleaning technique. The cleaning time is 10-20 minutes, and the frequency is 40-45 kHz; The cleaned nanofiber mesh composite material is subjected to surface conductive treatment by a gold plating process, the gold plating thickness is set to 5-10 nm, and the coating uniformity is treated by a DC magnetron sputtering method; Analyzing the surface morphology and fiber structure of the nanofiber mesh composite material based on a scanning electron microscope, obtaining a surface morphology image of the nanofiber mesh composite material, and calculating the fiber diameter distribution based on the surface morphology image to obtain fiber diameter data; The fiber diameter data is subjected to a normality test and the standard deviation is calculated to determine whether the uniformity of the fiber diameter distribution meets a preset value. If not, the parameters of the electrospinning device are adjusted until the uniformity of the fiber diameter distribution meets the preset value.

[0013] Furthermore, the step of immersing the nanofiber mesh composite material in an acidic solution for hydrolysis reaction, and covering the surface of the nanofiber mesh composite material after the hydrolysis reaction with a layer of biocompatible coating by chemical vapor deposition technology comprises: The nanofiber mesh composite material is immersed in an acidic solution with a pH value of 1 to 3 to perform a hydrolysis reaction; The nanofiber mesh composite material is reacted with a precursor gas through chemical vapor deposition to form a thin film on the surface of the nanofiber mesh composite material, wherein the precursor gas is at least one of silicon tetrachloride, dimethyldichlorosilane, and triethoxysilane.

[0014] The present application also discloses an absorbable excipient, which is prepared by the preparation method of the absorbable excipient as described in any of the above items, and the absorbable excipient includes: a polymer material, an inorganic material and nanoparticles. Calculated by mass percentage, the polymer material accounts for 66~81%, the inorganic material accounts for 9~27%, and the nanoparticles account for 5~10%.

[0015] Compared with the prior art, this application has the following beneficial effects: The preparation method of the absorbable auxiliary material of the present application adopts the steps of mixing the polymer material with the inorganic material and performing a heat treatment, which can effectively improve the compatibility of the composite material, put the composite material into a dissolving agent, mix it by ultrasonic oscillation method, make the mixture uniformly dispersed, add nanoparticles in the uniformly dispersed mixed solution, modify the nanoparticles by surface modifier, so that the nanoparticles can be more evenly dispersed in the composite solution, and enhance its interaction with the polymer material and the inorganic material, further spin the composite solution into a nanofiber mesh structure by electrostatic spinning technology, improve the surface area and porosity of the composite material, cover the surface of the nanofiber mesh composite material with a layer of biocompatible coating by hydrolysis reaction and chemical vapor deposition technology, significantly improve the biocompatibility of the material, and obtain the absorbable auxiliary material by washing with organic solvent and vacuum drying. In general, the preparation method provided by the present application significantly improves the performance of the absorbable auxiliary material by optimizing the selection of raw materials, improving the preparation process and finely controlling the material structure, and solves the problems of unstable material performance, uncontrollable degradation rate and poor biocompatibility existing in the prior art. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative labor.

[0017] The structures, proportions, sizes, etc. illustrated in the drawings of this specification are only used to match the contents disclosed in the specification so as to facilitate understanding and reading by persons familiar with this technology. They are not used to limit the conditions under which this application can be implemented, and therefore have no substantive technical significance. Any structural modification, change in proportion or adjustment of size, without affecting the effects and purposes that can be achieved by this application, should still fall within the scope of the technical contents disclosed in this application.

[0018] Figure 1 The figure is a schematic diagram of the overall steps of the preparation method of the absorbable excipient; Figure 2 A schematic diagram of the steps of an embodiment of a method for preparing an absorbable auxiliary material; Figure 3 The present invention is a schematic diagram of the steps of another embodiment of a method for preparing an absorbable auxiliary material. DETAILED DESCRIPTION

[0019] In order to make the purpose, features, and advantages of the invention of this application more obvious and easy to understand, the technical solutions in the embodiments of this application will be clearly and completely described below in conjunction with the drawings in the embodiments of this application. Obviously, the embodiments described below are only part of the embodiments of this application, not all of them. Based on the embodiments in this application, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of this application.

[0020] In the description of the present application, it should be understood that the terms "upper", "lower", "top", "bottom", "inside", "outside", etc., indicating the orientation or positional relationship, are based on the orientation or positional relationship shown in the drawings, and are only for the convenience of describing the present application and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as a limitation on the present application. It should be noted that when a component is considered to be "connected" to another component, it may be directly connected to the other component or there may be a centrally arranged component at the same time.

[0021] The technical solution of the present application is further explained below with reference to the accompanying drawings and through specific implementation methods.

[0022] refer to Figures 1 to 3 The present application provides a method for preparing an absorbable excipient, comprising: S1: Mixing a polymer material as a base material with an inorganic material, and heating the mixture to form a composite material; In step S1, a suitable polymer material (such as gelatin, chitosan or hyaluronic acid) is first selected as the substrate, and a suitable inorganic material such as hydroxyapatite or nano-silicon is selected to enhance the hardness and mechanical strength of the composite material. These polymer materials and inorganic materials are uniformly mixed in a certain proportion, for example, according to the mass ratio of polymer material: inorganic material = 70:30~90:10, so as to make the compatibility and uniform distribution between the components. After mixing, it is heated to a certain temperature (such as 150°C) to soften the polymer material, facilitate the combination with the inorganic material, and enhance the physical properties of the composite material by heat treatment. The heating process also helps to improve the interfacial adhesion between the polymer and the inorganic particles.

[0023] S2: putting the composite material into a solvent for mixing, and dispersing it uniformly by ultrasonic vibration to obtain a uniformly dispersed mixed solution; In step S2, select suitable solvent to dissolve or disperse the composite material. By selecting the polarity of the solvent and the property of the composite material, the material can be effectively dissolved or dispersed. The ultrasonic vibration method is further promoted to uniformly disperse the components in the composite material. The ultrasonic vibration can break the large particles or agglomerates in the composite material by producing cavitation effect, so that the large particles or agglomerates in the composite material are evenly distributed in the solution, so that subsequent nanoparticles are added and electrostatic spinning is processed. Through this step, the dispersibility of the composite material in the solvent is optimized, and the precipitation of nanoparticles is avoided, ensuring the stability and uniformity of the material in the spinning process.

[0024] S3: adding nanoparticles to the mixed solution to obtain a composite solution containing nanoparticles, wherein the surface of the nanoparticles is modified by a surface modifier; In step S3, select nanoparticle to add in the composite solution as strengthening component, nanoparticle has larger specific surface area and unique physical and chemical property, can significantly improve mechanical property, biocompatibility and cell adhesion ability of composite material.But the dispersibility of nanoparticle is poor, easily gathers.Therefore, before mixing with mixed solution, nanoparticle surface is carried out modification treatment, and modification method at least comprises and uses surface modifiers such as amino compound, quaternary ammonium salt, improves the compatibility of particle and base material, prevents the reunion of nanoparticle, improves its dispersibility in solution.Through this step, nanoparticle can be evenly distributed in the composite solution, forms stable composite solution.

[0025] S4: spinning the composite solution into a nanofiber mesh structure through an electrospinning device, placing the nanofiber mesh structure into a cross-linking furnace, and cross-linking and curing the nanofiber mesh structure under a nitrogen atmosphere to obtain a nanofiber mesh composite material; In step S4, the composite solution containing nanoparticles is converted into a nanofiber mesh structure by electrospinning technology. Electrospinning is a technology that stretches a polymer solution into fine fibers under high voltage. In this process, the composite solution is stretched to form fibers by the action of electric field force. The diameter of the fiber is at the nanometer scale. By adjusting the voltage, the distance between the nozzle and the collecting plate, and the flow rate of the solution, the diameter of the fiber and the tightness of the mesh structure can be controlled. The formation of the nanofiber mesh structure has multiple advantages, including a large specific surface area, which is conducive to the attachment, proliferation and differentiation of cells. The nanofiber mesh structure obtained by electrospinning is placed in a cross-linking furnace for curing. The purpose of cross-linking curing is to cause the polymer material to undergo a cross-linking reaction by heating, thereby improving the mechanical properties and chemical stability of the composite material. The cross-linking process is carried out under a nitrogen atmosphere to prevent oxidation reactions and ensure the stability of the material. The cross-linking treatment can enhance the structural stability of the nanofibers, so that the composite material has stronger mechanical strength, heat resistance and corrosion resistance, and also makes it easier to control the degradation rate of the material in the body. It is worth noting that the nitrogen atmosphere refers to creating an oxygen-deficient environment by introducing nitrogen in a closed reaction environment.

[0026] S5: immersing the nanofiber mesh composite material in an acidic solution for hydrolysis reaction, and covering a biocompatible coating on the surface of the nanofiber mesh composite material after the hydrolysis reaction by chemical vapor deposition technology; In step S5, the cross-linked and cured nanofiber mesh composite material is immersed in an acidic solution for a hydrolysis reaction. Through the action of the acidic solution, certain functional groups or small molecules in the composite material are removed, exposing structures or functional groups that are more conducive to cell attachment. After hydrolysis, the surface of the composite material will have more hydrophilicity and biocompatibility, providing favorable conditions for the subsequent deposition of biocompatible coatings. Then, a layer of biocompatible coating, such as polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP), etc., is deposited on the surface of the hydrolyzed nanofibers using chemical vapor deposition (CVD) technology. These coatings can significantly improve the biocompatibility of the composite material, reduce the immune response in the body, and promote cell attachment and proliferation.

[0027] S6: washing the nanofiber mesh composite material in an organic solvent to obtain a pure composite material, and subjecting the pure composite material to vacuum drying to prepare an absorbable auxiliary material.

[0028] In step S6, the nanofiber mesh composite material after surface coating treatment needs to be cleaned to remove excess solvent, chemical reaction residues and incompletely reacted substances. Organic solvents such as ethanol and acetone can be used for cleaning to ensure that there is no residue on the surface and achieve a pure effect. The cleaned composite material needs to be vacuum dried to remove moisture and solvent inside the material to ensure that it is dry, stable and convenient for storage. Ultimately, the material after vacuum drying will be made into an absorbable auxiliary material, which is suitable for various biomedical or environmentally friendly purposes. This step ensures the purity and stability of the final material obtained, and provides a guarantee for its effect in practical applications.

[0029] In steps S1-S6, the present application adopts the steps of mixing polymer materials with inorganic materials and performing heat treatment, which can effectively improve the compatibility of composite materials, make good combination between polymer substrate and inorganic materials, put the composite material into a solvent, mix it by ultrasonic vibration method, make the mixture uniformly dispersed, avoid phase separation or uneven phenomenon that may occur in traditional methods, and significantly improve the uniformity and stability of the composite material. Nanoparticles are added to the uniformly dispersed mixed solution, and the nanoparticles are modified by surface modifiers so that the nanoparticles can be more evenly dispersed in the composite solution, and enhance its interaction with polymer materials and inorganic materials, thereby improving the overall performance of the composite material. The composite solution is spun into a nanofiber mesh structure by electrostatic spinning technology, which increases the surface area and porosity of the composite material, improves the adsorption capacity of the material, and regulates its degradation rate to a certain extent. In particular, in the cross-linking and curing step, by cross-linking under a nitrogen atmosphere, the structure of the nanofiber can be effectively fixed, and its mechanical properties and biodegradability can be improved, so that the obtained nanofiber mesh composite material not only performs better in mechanical properties, but also can achieve a more controllable degradation rate. Then, by hydrolysis reaction and chemical vapor deposition technology, a layer of biocompatible coating is covered on the surface of the nanofiber mesh composite material, which can significantly improve the biocompatibility of the material and avoid the immune response or biological rejection problems that may occur when the traditional composite material is used in vivo. The coating coverage enables the composite material to better interact with the surrounding tissue in the organism and promote the process of wound repair or tissue regeneration. Finally, by organic solvent cleaning and vacuum drying treatment, the purity and stability of the composite material are ensured, so that it has higher safety and reliability in clinical applications. In general, the preparation method provided by the present application significantly improves the performance of absorbable excipients by optimizing raw material selection, improving preparation technology and finely controlling material structure, solves the problems of unstable material performance, uncontrollable degradation rate and poor biocompatibility in the prior art, and has broad application prospects, especially suitable for wound repair, tissue engineering and other biomedical materials.

[0030] In one embodiment, the polymer material is at least one of gelatin, chitosan or hyaluronic acid, and the inorganic material is at least one of hydroxyapatite or nano-silicon. According to the mass ratio percentage, the polymer material accounts for 70-90% of the composite material, and the inorganic material accounts for 10-30%. The dissolving agent is at least one of chloroform, dichloromethane or ethanol. According to the mass ratio percentage, the dissolving agent accounts for 5-15% of the mixed solution, and the rest is the composite material. The nanoparticles are at least one of zinc oxide, nano-silicon dioxide or nano-cellulose, and the surface modifier is aminosilane. Through the above ratio and selection, the composite material can have good biocompatibility and suitable mechanical strength, while maintaining the degradability of the material. In the preparation process, by accurately controlling the proportion of each component and the reaction conditions, an absorbable excipient with specific properties can be obtained to meet the needs of different clinical applications. For example, a mixture of gelatin and chitosan can provide a good cell attachment and proliferation environment, while the addition of hydroxyapatite can enhance the mechanical properties of the material and promote the growth of bone tissue. By optimizing the ratio of these components, absorbable excipients suitable for different tissue engineering applications can be prepared, such as bone repair, soft tissue regeneration, etc. In addition, by adjusting the types of nanoparticles and surface modifiers, the surface properties of the material, such as hydrophilicity and antibacterial properties, can be further improved, thereby broadening its application range in the biomedical field.

[0031] In one embodiment, the step of placing the composite material into a solvent for mixing, and dispersing it uniformly by ultrasonic vibration to obtain a uniformly dispersed mixed solution comprises: S21: cutting the composite material into a predetermined size range to obtain composite material particles, wherein the size range is 50-500 microns; S22: mixing the composite material particles and the dissolving agent and soaking them for 1 to 2 hours to obtain a preliminary soaking mixed solution, placing the soaking mixed solution into an ultrasonic oscillation device, setting the ultrasonic oscillation frequency to 20 to 40 kHz, the oscillation power to 150 to 300 W, and controlling the oscillation time to 15 to 30 minutes to obtain a preliminary dissolved solution; S23: heating the preliminary dissolved solution to a temperature range of 40-60° C. and maintaining the constant temperature for 20-60 minutes to obtain a pretreated uniformly dispersed solution; S24: performing a particle size distribution test on the uniformly dispersed solution based on a dynamic light scattering method to determine whether the particle size dispersion in the uniformly dispersed solution is less than 10%; S25: If both are yes, a uniformly dispersed mixed solution is obtained; if both are no, the ultrasonic oscillation time and power are adjusted until the particle size dispersion in the uniformly dispersed solution is less than 10%.

[0032] In step S21-S25, the composite material is cut to a predetermined size range to obtain composite material particles of 50 to 500 microns in size, so that the composite material can effectively contact with the solvent in the subsequent dissolution and dispersion process, which helps it to produce a uniform dispersion effect during the ultrasonic oscillation process. The composite material particles cut to this size range are not only convenient for the penetration and dissolution of the solvent, but also make the particles more easily dispersed during ultrasonic oscillation. If the particles are too large, it may cause uneven dispersion, thereby affecting the uniformity of the final solution. If the particles are too small, precipitation may occur, affecting the ultrasonic oscillation effect. The cut composite material particles are mixed with the solvent and soaked for 1 to 2 hours to obtain a preliminary soaking mixed solution, so that the composite material particles can fully contact with the solvent, gradually dissolve or disperse, break the molecular structure inside the composite material, and make it easier to disperse evenly in subsequent ultrasonic oscillations. The soaking time of 1 to 2 hours is set as an equilibrium time, so that the solvent can penetrate into the composite material particles, but will not cause excessive dissolution or incomplete dispersion, and the preliminary soaked mixed solution is placed in an ultrasonic oscillation device for further processing. The frequency of ultrasonic oscillation is set to 20~40 kHz, the oscillation power is set to 150~300 W, and the oscillation time is set to 15~30 minutes. The cavitation effect is generated by high-frequency vibration waves, resulting in rapid dispersion of composite material particles. High frequency and moderate power can produce strong cavitation, thereby effectively breaking the agglomeration and aggregation between composite material particles and promoting uniform dispersion of particles. The experimental conditions can be optimized to ensure that a uniformly dispersed mixed solution is obtained. After the initial dissolution solution is subjected to ultrasonic oscillation, it is heated to 40~60℃ and is kept at this temperature for 20~60 minutes. The purpose of the heating treatment is to further accelerate the dissolution or dispersion of composite material particles and ensure that the dissolution effect of the solvent is fully exerted. Appropriate temperature can increase solubility, promote interaction between particles, and enhance dispersibility. During the heating process, the isothermal reaction time is controlled between 20 and 60 minutes. This time range ensures the balance of the dissolution process, which can not only avoid the volatilization or degradation of the solvent due to too long a time, but also ensure the full dispersion of the material in the solution. Finally, the obtained solution is tested for particle size distribution. Dynamic light scattering (DLS) is used to analyze the particle size distribution of the solution to determine whether the dispersion of the particles in the obtained solution is less than 10%. DLS technology can accurately measure the size and distribution of particles in liquids. If the test results show that the particle size dispersion is less than 10%, it indicates that the particles in the solution are evenly dispersed and can proceed to the subsequent steps. If the particle size dispersion is greater than 10%, the time or power of the ultrasonic oscillation needs to be adjusted until the ideal dispersion effect is achieved. The purpose of adjusting the oscillation time and power is to further increase the intensity of the ultrasonic oscillation so that the particles can be dispersed more effectively, thereby improving the uniformity and stability of the solution.

[0033] In one embodiment, the step of adding nanoparticles to the mixed solution to obtain a composite solution containing nanoparticles, wherein the surface of the nanoparticles is modified by a surface modifier, comprises: The nanoparticles are immersed in a solution containing ethanol and deionized water for ultrasonic cleaning to remove pollutants and impurities that may exist on the surface of the particles, thereby obtaining nanoparticles with preliminarily cleaned surfaces; Dispersing the washed nanoparticles into an acetonitrile solution, adding the surface modifier, the modification time is 2 to 4 hours, and stirring so that the modifier is uniformly adsorbed on the surface of the nanoparticles to obtain surface-modified nanoparticles; The surface-modified nanoparticles are added to the mixed solution, and the mixed solution is stirred using a magnetic stirrer for 1 to 2 hours to obtain a composite solution containing surface-modified nanoparticles, wherein the nanoparticles account for 1% to 5% by mass, and the rest is the mixed solution.

[0034] In this embodiment, the surface of the nanoparticles may be attached with oil, dust or other reactive substances. These impurities will affect the surface characteristics of the nanoparticles and further affect their dispersibility in the composite solution. The nanoparticles are immersed in a solution containing ethanol and deionized water for ultrasonic cleaning to remove the pollutants and impurities that may exist on the surface of the nanoparticles. Ethanol has good dissolving power and can remove grease and other organic pollutants, while deionized water helps to clean water-soluble impurities. The effect of ultrasonic cleaning is to promote the removal of impurities on the surface of the particles through the cavitation effect generated by high-frequency vibration, while preventing the agglomeration between particles. The surface of the cleaned nanoparticles is modified by adding a surface modifier to the acetonitrile solution. The main purpose of the surface modification is to improve the dispersibility of the nanoparticles, enhance their stability in the solution, and optimize their interaction with other components (such as composite materials). By adding a surface modifier to the acetonitrile solution, the modifier can react chemically or physically with the surface of the nanoparticles, thereby changing the surface properties of the nanoparticles. The selection of the modifier depends on the type of nanoparticles and their application requirements. Surfactants, polymers, inorganic molecules, etc. can be selected. These modifiers can be fixed on the surface of the nanoparticles by electrostatic adsorption, coordination or chemical bonding. The surface-modified nanoparticles are added to the prepared mixed solution, and the mixed solution is stirred using a magnetic stirrer for 1 to 2 hours to ensure that the nanoparticles are evenly dispersed in the solution. The role of magnetic stirring is to ensure that the nanoparticles are evenly distributed in the solution and to avoid agglomeration of the nanoparticles. Through stirring, the surface-modified nanoparticles can form a stable dispersion system in the mixed solution to obtain a composite solution containing surface-modified nanoparticles.

[0035] In one embodiment, the step of spinning the composite solution into a nanofiber mesh structure through an electrospinning device, placing the nanofiber mesh structure in a cross-linking furnace, and cross-linking and curing the nanofiber mesh structure under a nitrogen atmosphere to obtain a nanofiber mesh composite material comprises: S41: spraying the composite solution through an electrospinning device, controlling the spraying voltage of the electrospinning device to be 15-30 kV, the electrode spacing to be 10-20 cm, and the spraying flow rate to be 0.1-0.5 mL / h, and spinning the composite solution to obtain a pre-spun nanofiber mesh structure; S42: placing the nanofiber network structure in an oven at a temperature of 50-80° C. for heat treatment for 2-4 hours, and immersing the heat-treated nanofiber network structure in a crosslinking agent solution for 30-60 minutes, so that the crosslinking agent reacts with the functional groups on the surface of the nanofibers to obtain a pre-crosslinked nanofiber network structure, wherein the crosslinking agent solution is polyisocyanate or polyol, and the concentration of the crosslinking agent is 5-20 wt% calculated by mass ratio percentage; S43: placing the pre-crosslinked nanofiber network structure into a crosslinking furnace, curing it in a nitrogen atmosphere, controlling the furnace temperature to 120-180° C., and the curing time to 2-4 hours, to obtain a crosslinked and cured nanofiber network composite material.

[0036] In this embodiment, the composite solution is sprayed through an electrospinning device to form a pre-spun nanofiber mesh structure. The working principle of electrospinning is to use a high voltage electric field to generate electrostatic force on the polymer chains in the solution, stretch and gradually solidify to form fine fibers. In this embodiment, the spray voltage is set to 15~30 kV. This voltage range can effectively spray the solution and form fine nanofibers. The electrode spacing is 10~20 cm. This spacing ensures the appropriate electric field strength, helps the stability of the spinning process, and controls the diameter of the fiber. The spray flow rate is 0.1~0.5 mL / h. Too fast a flow rate may cause uneven fibers or spinning failure, while too slow a flow rate may affect production efficiency. By controlling these parameters, a uniform and well-distributed nanofiber mesh structure can be obtained. The nanofiber mesh structure is placed in an oven at 50-80°C for heat treatment for 2~4 hours to remove the solvent residue on the fiber surface, help the fiber solidify and increase its stability. The selection of heat treatment temperature and time needs to be balanced to avoid excessive shrinkage or damage to the fiber. After heat treatment, the nanofiber mesh structure will be immersed in a crosslinking agent solution for pre-crosslinking, and the molecular chains between the nanofibers will be connected by chemical reaction, thereby improving the mechanical strength, thermal stability and chemical stability of the fiber. The crosslinking agent used is polyisocyanate or polyol, which can react with the functional groups on the fiber surface to form a crosslinked structure. The concentration of the crosslinking agent is 5-20 wt%, and the degree of crosslinking will vary depending on the concentration of the crosslinking agent and the reactivity of the surface functional groups of the fiber. The soaking time is controlled at 30-60 minutes so that the crosslinking agent can fully penetrate into the fiber surface and react with the functional groups on the fiber surface to ensure the uniformity of crosslinking. Finally, the pre-crosslinked nanofiber mesh structure is placed in a crosslinking furnace for curing. The curing process needs to be carried out in a nitrogen atmosphere, which is mainly to avoid oxygen interference with the crosslinking reaction and prevent the occurrence of oxidation reaction. The curing temperature is controlled between 120-180°C and the curing time is 2-4 hours. This temperature and time range is sufficient to ensure that the crosslinking reaction between the crosslinking agent and the fiber is completed, and the structure of the material is stabilized to obtain a crosslinked and cured nanofiber mesh composite material.

[0037] In one embodiment, after the step of obtaining the cross-linked and cured nanofiber mesh composite material, the method further comprises: The nanofiber mesh composite material is cleaned in an anhydrous ethanol solution using an ultrasonic cleaning technique. The cleaning time is 10-20 minutes, and the frequency is 40-45 kHz; The cleaned nanofiber mesh composite material is subjected to surface conductive treatment by a gold plating process, the gold plating thickness is set to 5-10 nm, and the coating uniformity is treated by a DC magnetron sputtering method; Analyzing the surface morphology and fiber structure of the nanofiber mesh composite material based on a scanning electron microscope, obtaining a surface morphology image of the nanofiber mesh composite material, and calculating the fiber diameter distribution based on the surface morphology image to obtain fiber diameter data; The fiber diameter data is subjected to a normality test and the standard deviation is calculated to determine whether the uniformity of the fiber diameter distribution meets a preset value. If not, the parameters of the electrospinning device are adjusted until the uniformity of the fiber diameter distribution meets the preset value.

[0038] In the present embodiment, after the nanofiber mesh composite material obtained by cross-linking and curing has formed a preliminary structure, it is cleaned using ultrasonic cleaning technology, and the high-frequency vibration of ultrasound is used to generate tiny bubbles. The strong impact generated by these bubbles when they break can remove impurities or solvent residues on the fiber surface and pores. This process is crucial for improving the surface cleanliness of nanofibers and removing possible pollutants. In the present embodiment, anhydrous ethanol solution is used for cleaning. Anhydrous ethanol can quickly dissolve and remove organic impurities that may exist on the fiber surface as a solvent. It is also a volatile solvent that can evaporate quickly after cleaning to avoid affecting subsequent processes. The cleaning time is controlled to 10 to 20 minutes, which can ensure the adequacy of cleaning and avoid damage to the material caused by too long cleaning. The ultrasonic frequency is 40 to 45kHz, and this frequency range can generate enough small bubbles to enhance the cleaning effect, but it will not produce too much mechanical force on the material. After cleaning, the nanofiber mesh composite material will be subjected to surface conductive treatment, and gold plating technology is used. Gold plating can provide good conductivity for nanofibers, which is very important for the electrical properties of nanofibers and subsequent experimental tests, especially in electrochemical sensors, electronic components or other applications that require conductive properties. The thickness of gold plating is 5~10 nm. This thickness range can effectively improve the conductivity of the fiber while maintaining the flexibility and transparency of the material. The gold plating process adopts the DC magnetron sputtering method. Through DC magnetron sputtering, the metal target will be sputtered and deposited on the surface of the material under the action of gas, which can evenly form a thin metal layer, with high deposition efficiency and good coating uniformity, which can ensure that the surface of the nanofiber mesh composite material is uniformly coated with a conductive coating, thereby improving its electrical properties. After the surface gold plating treatment is completed, based on scanning electron microscopy (SEM) analysis, SEM is a high-resolution imaging technology that can clearly display the surface morphology and structure of the nanofiber mesh composite material. Through scanning electron microscopy, the morphology of the fiber can be directly observed, the surface quality of the material and the uniformity of the fiber can be evaluated, and the SEM image can reveal whether the fiber has obvious defects, aggregation or inhomogeneity, and provide quantitative visual information. Based on the surface morphology image obtained by SEM, the diameter distribution of the nanofiber is analyzed, the diameter data of the fiber is calculated, and statistical analysis is performed on it, and the fiber diameter data is tested for normality to evaluate whether its distribution meets the expected uniformity requirements. The normality test is used to determine whether the data conforms to the normal distribution. If the fiber diameter distribution conforms to the normal distribution, it means that the size uniformity of the fiber is good, and its mechanical properties and surface properties are relatively stable. If it does not conform to the normal distribution, it means that there is a large fluctuation in the diameter of the fiber, and the process parameters need to be further adjusted. If the distribution of the fiber diameter does not meet the preset uniformity requirements, the embodiment points out that the parameters of the electrospinning equipment need to be adjusted.Multiple factors in the electrospinning process, such as voltage, jet flow rate, and electrode spacing, will affect the diameter and morphology of the fibers. If the diameter distribution of the fibers is uneven, the results can usually be optimized by adjusting these parameters. For example, increasing the voltage may help stretch the fibers and reduce the diameter; changing the jet flow rate can also affect the speed of fiber formation and thus regulate its size. It is worth noting that the preset uniformity requirements can be determined experimentally and set according to the needs of the specific application.

[0039] In one embodiment, the step of immersing the nanofiber mesh composite material in an acidic solution for hydrolysis reaction, and covering the surface of the nanofiber mesh composite material after the hydrolysis reaction with a biocompatible coating by chemical vapor deposition technology comprises: The nanofiber mesh composite material is immersed in an acidic solution with a pH value of 1 to 3 to perform a hydrolysis reaction; The nanofiber mesh composite material is reacted with a precursor gas through chemical vapor deposition to form a thin film on the surface of the nanofiber mesh composite material, wherein the precursor gas is at least one of silicon tetrachloride, dimethyldichlorosilane, and triethoxysilane.

[0040] In this embodiment, the nanofiber mesh composite material is immersed in an acidic solution for hydrolysis reaction, and the pH value ranges from 1 to 3, so as to chemically modify the surface of the nanofiber. The hydrolysis reaction promotes the generation or change of functional groups on the fiber surface through acid catalysis, thereby enhancing the hydrophilicity, surface activity and subsequent chemical reaction ability of the material, because in a strong acid environment, certain chemical bonds on the fiber surface (such as silicon oxygen bonds, ester bonds, etc.) will break and hydrolyze, which helps to expose more active groups and further improve the surface reactivity of the material. After the hydrolysis reaction is completed, the surface of the nanofiber mesh composite material has a high activity. Next, a biocompatible film is deposited on the fiber surface by chemical vapor deposition (CVD) technology. By introducing a gas precursor into the reaction chamber and under appropriate temperature and pressure conditions, the gas reacts with the substrate to form a solid film. The precursor gas includes silicon tetrachloride (SiCl 4), dimethyldichlorosilane (DMDCS) and triethoxysilane (TEOS), all of which contain silicon and are common precursors for depositing silicon-based coatings. Through chemical vapor deposition reactions, silicon-based gases react with the active sites after surface hydrolysis to form a uniform film. The main function of the film is to provide a biocompatible coating to enhance the biocompatibility of nanofibers, allowing them to exist in the biological environment for a long time without causing an immune response. The film deposited by the CVD reaction is not only biocompatible, but also improves the surface properties of the fiber. The biocompatible coating can effectively reduce the immune response of the fiber in the body and improve its stability and safety in the biological environment. This coating prevents the fiber from direct contact with other cells or tissues in the body, thereby reducing adverse reactions such as allergies and rejection.

[0041] It is worth noting that all the devices described in this application are achievable through the prior art, the algorithms described are all mature algorithms based on the prior art, and in the preparation process, the chemical substances and conditions used are within the safe range and will not cause harm to the operator or the environment. In addition, the prepared absorbable excipients have good degradation performance in vivo, and their degradation products are non-toxic to the human body and can be naturally absorbed by the human body or excreted from the body through metabolism. In practical applications, the excipients can be used in various medical fields such as surgical sutures, tissue engineering scaffolds, and drug sustained-release carriers, providing patients with safer and more effective treatment options.

[0042] The present invention also discloses an absorbable excipient, which is prepared by the preparation method of the absorbable excipient as described in any one of the above items. The absorbable excipient comprises: a polymer material, an inorganic material and nanoparticles. Calculated by mass percentage, the polymer material accounts for 66-81%, the inorganic material accounts for 9-27%, and the nanoparticles accounts for 5-10%.

[0043] As described above, the above embodiments are only used to illustrate the technical solutions of the present application, rather than to limit them. Although the present application has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present application.

Claims

1. A method for preparing an absorbable auxiliary material, characterized in that: include: Mixing a polymer material as a base material with an inorganic material, and heating the mixture to form a composite material; The composite material is placed in a solvent for mixing, and dispersed evenly by ultrasonic vibration to obtain a uniformly dispersed mixed solution; Adding nanoparticles to the mixed solution to obtain a composite solution containing nanoparticles, wherein the surfaces of the nanoparticles are modified by a surface modifier; The composite solution is spun into a nanofiber mesh structure by an electrostatic spinning device, the nanofiber mesh structure is placed in a cross-linking furnace, and the nanofiber mesh structure is cross-linked and cured under a nitrogen atmosphere to obtain a nanofiber mesh composite material; The nanofiber mesh composite material is immersed in an acidic solution to perform a hydrolysis reaction, and a biocompatible coating is coated on the surface of the nanofiber mesh composite material after the hydrolysis reaction by chemical vapor deposition technology; The nanofiber mesh composite material is placed in an organic solvent for washing to obtain a pure composite material, and the pure composite material is subjected to vacuum drying to prepare an absorbable auxiliary material.

2. The method for preparing the absorbable auxiliary material according to claim 1, characterized in that: The polymer material is at least one of gelatin, chitosan or hyaluronic acid, and the inorganic material is at least one of hydroxyapatite or nano-silicon. Calculated by weight percentage, in the composite material, the polymer material accounts for 70-90%, and the inorganic material accounts for 10-30%.

3. The method for preparing the absorbable auxiliary material according to claim 1, characterized in that: The solvent is at least one of chloroform, dichloromethane or ethanol. Calculated by weight percentage, the solvent accounts for 5-15% of the mixed solution, and the rest is the composite material.

4. The method for preparing the absorbable auxiliary material according to claim 1, characterized in that: The nanoparticles are at least one of zinc oxide, nano-silicon dioxide or nano-cellulose, and the surface modifier is aminosilane.

5. The method for preparing the absorbable auxiliary material according to claim 1, characterized in that: The step of placing the composite material into a solvent for mixing, and dispersing it uniformly by ultrasonic vibration to obtain a uniformly dispersed mixed solution comprises: Cutting the composite material into a predetermined size range to obtain composite material particles, wherein the size range is 50-500 microns; The composite material particles and the dissolving agent are mixed and soaked for 1 to 2 hours to obtain a preliminary soaking mixed solution, and the soaking mixed solution is placed in an ultrasonic oscillation device, the ultrasonic oscillation frequency is set to 20 to 40 kHz, the oscillation power is set to 150 to 300 W, and the oscillation time is controlled to be 15 to 30 minutes to obtain a preliminary dissolved solution; The preliminary dissolved solution is heated to a temperature range of 40-60° C. and kept at a constant temperature for 20-60 minutes to obtain a pre-treated uniformly dispersed solution; Performing a particle size distribution test on the uniformly dispersed solution based on a dynamic light scattering method to determine whether the particle size dispersion in the uniformly dispersed solution is less than 10%; If both are positive, a uniformly dispersed mixed solution is obtained; if both are negative, the ultrasonic oscillation time and power are adjusted until the particle size dispersion in the uniformly dispersed solution is less than 10%.

6. The method for preparing the absorbable auxiliary material according to claim 1, characterized in that: The step of adding nanoparticles to the mixed solution to obtain a composite solution containing nanoparticles, wherein the surface of the nanoparticles is modified by a surface modifier, comprises: The nanoparticles are immersed in a solution containing ethanol and deionized water for ultrasonic cleaning to remove pollutants and impurities that may exist on the surface of the particles, thereby obtaining nanoparticles with preliminarily cleaned surfaces; Dispersing the washed nanoparticles into an acetonitrile solution, adding the surface modifier, the modification time is 2 to 4 hours, and stirring so that the modifier is uniformly adsorbed on the surface of the nanoparticles to obtain surface-modified nanoparticles; The surface-modified nanoparticles are added to the mixed solution, and the mixed solution is stirred using a magnetic stirrer for 1 to 2 hours to obtain a composite solution containing surface-modified nanoparticles, wherein the nanoparticles account for 1% to 5% by mass, and the rest is the mixed solution.

7. The method for preparing the absorbable auxiliary material according to claim 1, characterized in that: The step of spinning the composite solution into a nanofiber mesh structure through an electrospinning device, placing the nanofiber mesh structure in a cross-linking furnace, and cross-linking and curing the nanofiber mesh structure under a nitrogen atmosphere to obtain a nanofiber mesh composite material comprises: The composite solution is sprayed through an electrospinning device, the spray voltage of the electrospinning device is controlled to be 15-30 kV, the electrode spacing is 10-20 cm, and the spray flow rate is 0.1-0.5 mL / h, and the composite solution is spun to obtain a pre-spun nanofiber mesh structure; The nanofiber network structure is placed in an oven at a temperature of 50-80° C. for heat treatment for 2-4 hours, and the heat-treated nanofiber network structure is immersed in a cross-linking agent solution for 30-60 minutes, so that the cross-linking agent reacts with the functional groups on the surface of the nanofibers to obtain a pre-cross-linked nanofiber network structure, wherein the cross-linking agent solution is polyisocyanate or polyol, and the concentration of the cross-linking agent is 5-20wt% calculated by mass ratio percentage; The pre-crosslinked nanofiber mesh structure is placed in a crosslinking furnace and cured in a nitrogen atmosphere. The furnace temperature is controlled at 120-180° C. and the curing time is 2-4 hours to obtain a crosslinked and cured nanofiber mesh composite material.

8. The method for preparing the absorbable auxiliary material according to claim 7, characterized in that: After the step of obtaining the cross-linked and cured nanofiber mesh composite material, the method further comprises: The nanofiber mesh composite material is cleaned in an anhydrous ethanol solution using an ultrasonic cleaning technique. The cleaning time is 10-20 minutes, and the frequency is 40-45 kHz; The cleaned nanofiber mesh composite material is subjected to surface conductive treatment by a gold plating process, the gold plating thickness is set to 5-10 nm, and the coating uniformity is treated by a DC magnetron sputtering method; Analyzing the surface morphology and fiber structure of the nanofiber mesh composite material based on a scanning electron microscope, obtaining a surface morphology image of the nanofiber mesh composite material, and calculating the fiber diameter distribution based on the surface morphology image to obtain fiber diameter data; The fiber diameter data is subjected to a normality test and the standard deviation is calculated to determine whether the uniformity of the fiber diameter distribution meets a preset value. If not, the parameters of the electrospinning device are adjusted until the uniformity of the fiber diameter distribution meets the preset value.

9. The method for preparing the absorbable auxiliary material according to claim 1, characterized in that: The step of immersing the nanofiber mesh composite material in an acidic solution for hydrolysis reaction, and covering the surface of the nanofiber mesh composite material after the hydrolysis reaction with a layer of biocompatible coating by chemical vapor deposition technology comprises: The nanofiber mesh composite material is immersed in an acidic solution with a pH value of 1 to 3 to perform a hydrolysis reaction; The nanofiber mesh composite material is reacted with a precursor gas through chemical vapor deposition to form a thin film on the surface of the nanofiber mesh composite material, wherein the precursor gas is at least one of silicon tetrachloride, dimethyldichlorosilane, and triethoxysilane.

10. An absorbable auxiliary material, characterized in that: The absorbable excipient is prepared by the preparation method of the absorbable excipient according to any one of claims 1 to 9, wherein the absorbable excipient comprises: a polymer material, an inorganic material and nanoparticles, and calculated by mass percentage, the polymer material accounts for 66-81%, the inorganic material accounts for 9-27%, and the nanoparticles accounts for 5-10%.

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