L-polylactic acid / nano-zinc oxide hybrid material as well as preparation method and application thereof

Abstract

The invention provides a poly-L-lactic acid / nano-zinc oxide hybrid material and a preparation method and application thereof, and belongs to the technical field of organic / inorganic composites.The hybrid material comprises poly-L-lactic acid and nano-zinc oxide, the preparation method comprises the following steps that nano-zinc oxide with the surface containing hydroxyl is used for in-situ initiation of ring-opening polymerization of L-lactide, and the poly-L-lactic acid / nano-zinc oxide hybrid material is obtained; the poly-L-lactic acid hybrid material combined with nano-zinc oxide through chemical bonds is prepared; the in-situ initiation polymerization reaction is carried out under the condition of a catalyst, and catalyst residues are removed by a method of dissolving with a solvent and re-precipitating in a precipitating agent before compounding with nano-zinc oxide; the polymerization mode is bulk polymerization or solution polymerization; the preparation method provided by the invention can be used for synthesizing the poly-L-lactic acid / nano-zinc oxide hybrid material, and solves the problems of poor compatibility between nanoparticles and a matrix interface, easy agglomeration and infirm combination when the poly-L-lactic acid / nano-zinc oxide composite material is prepared by a traditional physical blending method.

Description

Technical Field

[0001] This invention belongs to the field of organic / inorganic composite materials technology, specifically, it relates to a L-polylactic acid / nano zinc oxide hybrid material and its preparation method and application. Background Technology

[0002] Polylactic acid (PLLA), a typical representative of aliphatic polyesters, is derived from renewable plant resources. With its excellent biocompatibility and biodegradability, it is ultimately metabolized into carbon dioxide and water in the human body, avoiding the risk of secondary damage caused by long-term retention. Therefore, it occupies an important position in the field of high-end medical devices. Its high stereoregularity endows it with excellent crystallinity and mechanical strength, enabling it to withstand physiological loads and maintain structural integrity. It is widely used as a bone fixation material, tissue engineering scaffold, and other load-bearing implants. However, the degradation behavior of PLLA in the physiological environment exhibits significant nonlinear characteristics. Its ester bond hydrolysis process has an autocatalytic effect, and the degradation rate is difficult to match synchronously with the tissue regeneration process, often leading to mechanical support failure before the maturation of new tissue. More importantly, the degradation intermediate product lactic acid accumulates locally around the implant, significantly lowering the pH of body fluids and forming an acidic microenvironment. This not only accelerates the material's own degradation but also easily triggers aseptic inflammatory reactions, inhibits cell activity, and hinders tissue ingrowth. Furthermore, pure PLLA materials themselves lack bioactive functions and have limited interfacial integration capabilities with host tissues, making it difficult to actively promote osteoinduction or angiogenesis. Their surface hydrophobicity also hinders cell adhesion and proliferation, and they lack antibacterial capabilities, resulting in a high risk of infection after implantation. To address these shortcomings, introducing inorganic bioactive components has become an important modification strategy, with zinc oxide being particularly prominent. Under physiological conditions, nano-zinc oxide can slowly release zinc ions, penetrate bacterial cell walls to interfere with their metabolic enzyme systems and inhibit biofilm formation, exhibiting broad-spectrum antibacterial activity. Simultaneously, it promotes bone tissue repair through multi-dimensional synergistic effects by regulating osteogenic signaling pathways, inhibiting osteoclast differentiation, and promoting angiogenesis. However, when traditional physical blending methods disperse nano-zinc oxide in a PLLA matrix, poor interfacial compatibility easily leads to particle aggregation, resulting in uneven distribution, unstable functional performance, and weak interfacial bonding affecting the mechanical enhancement effect, making large-scale stable preparation difficult. Summary of the Invention

[0003] In view of this, the present invention provides a polylactic acid / nano zinc oxide hybrid material, its preparation method and application, which solves the problems of poor compatibility between nanoparticles and matrix interface, easy agglomeration and weak bonding when preparing polylactic acid / nano zinc oxide composite materials by traditional physical blending method.

[0004] This invention is implemented as follows:

[0005] This invention provides a polylactic acid / nano zinc oxide hybrid material and its preparation method, comprising the following steps:

[0006] L-lactide, nano zinc oxide and catalyst are directly subjected to bulk polymerization or in situ polymerization in organic solvents to obtain the polymerization product.

[0007] The polymerization product is dissolved in an organic solvent and then reprecipitated in a precipitant to remove residual catalyst, thereby obtaining purified L-polylactic acid / nano zinc oxide hybrid material.

[0008] The technical advantages of the L-polylactic acid / nano zinc oxide hybrid material and its preparation method provided by this invention are as follows: By directly polymerizing L-lactide, nano zinc oxide, and a catalyst in bulk or in situ, and combining this with a purification process involving solvent dissolution and precipitant reprecipitation, polymerization and compounding are completed in one step, significantly simplifying the complex process of traditional multi-step modification. This process ensures that nano zinc oxide is in full contact with and uniformly dispersed in the polylactic acid chain during polymerization. At the same time, the reprecipitation effectively removes residual catalyst, reduces the cytotoxicity of the material, and improves biocompatibility. The overall process is highly controllable, reproducible, and conducive to large-scale production.

[0009] Based on the above technical solution, the L-polylactic acid / nano zinc oxide hybrid material and its preparation method of the present invention can be further improved as follows:

[0010] The mass ratio of L-lactide, nano zinc oxide, and catalyst is 5000:1~2:2~30.

[0011] The beneficial effects of adopting the above-mentioned improved scheme are as follows: the mass ratio of L-lactide, nano zinc oxide and catalyst is 5000:1~2:2~30. This ratio range allows nano zinc oxide to maintain an appropriate loading in the polylactic acid matrix, which not only fully exerts its antibacterial, osteogenic induction and other biological activities, but also avoids nanoparticle agglomeration and material mechanical property deterioration caused by excessive content. At the same time, the amount of catalyst is sufficient to ensure that the polymerization reaction is fully initiated and effectively removed in the subsequent purification process, thus achieving a balance between material performance and process feasibility.

[0012] Furthermore, when the polymerization reaction is in situ polymerization, the mass ratio of the L-lactide to the volume of the organic solvent is 1~2.5g:1~10mL.

[0013] The beneficial effects of adopting the above-mentioned improved scheme are as follows: the mass ratio of L-lactide to organic solvent is 1~2.5g:1~10mL. This amount of solvent can reasonably adjust the viscosity of the reaction system, promote the full mixing and mass transfer of monomers, nanoparticles and catalysts, and ensure that the in-situ polymerization reaction proceeds uniformly. This ratio avoids the insufficient fluidity and uneven mixing of the system caused by too little solvent, and also prevents the decrease in reaction rate and the burden of subsequent solvent recovery caused by too much solvent, thus optimizing the reaction efficiency and process economy.

[0014] Furthermore, the organic solvent is selected from at least one of dichloromethane, chloroform, toluene, ethyl acetate, acetone, and tetrahydrofuran.

[0015] The beneficial effects of adopting the above-mentioned improved scheme are as follows: the selected organic solvents include at least one of dichloromethane, trichloromethane, toluene, ethyl acetate, acetone, and tetrahydrofuran. These solvents have good solubility for L-lactide monomer and the selected catalyst, and at the same time have good wettability for the surface of nano zinc oxide, which can form a uniform and stable reaction dispersion system; the solvents have moderate boiling points, are easy to remove by vacuum distillation or washing after the reaction is completed, and are compatible with the reprecipitation process, ensuring the purification effect of the final product.

[0016] Furthermore, the average particle size of the nano-zinc oxide is 5~100nm.

[0017] The beneficial effects of adopting the above-mentioned improved scheme are as follows: the average size range of the nano-zinc oxide particles used for in-situ initiation polymerization and composite is limited to 5~100nm. Nanoparticles in this size range have a large specific surface area and surface reactivity, which can fully contact and participate in the reaction with L-lactide monomer and polylactic acid segments, which is conducive to the formation of stable chemical bond connections. At the same time, this size range can avoid particle agglomeration caused by excessively small particle size and stress concentration effect caused by excessively large particle size, ensuring the uniformity of the microstructure and the stability of the macroscopic properties of the hybrid material.

[0018] Furthermore, the reaction temperature of the polymerization reaction is 80~140℃.

[0019] The beneficial effects of adopting the above-mentioned improved scheme are as follows: the in-situ polymerization reaction temperature is 80~140℃, which is higher than the melting point of L-lactide and provides sufficient activation energy for the catalyst, so that the polymerization reaction can be carried out at a reasonable rate; at the same time, the upper limit of the temperature is strictly controlled below the thermal degradation temperature of polylactic acid, which effectively avoids the breakage of polymer chains and the decrease in molecular weight during the polymerization process, ensures the molecular weight and structural integrity of the product, and achieves dual optimization of reaction kinetics and product quality.

[0020] Furthermore, the catalyst is selected from at least one of zinc oxide, zinc acetate, zinc octanoate, zinc isooctanoate, zinc trifluoromethanesulfonate, zinc L-carnosine, zinc acetylacetonate, β-diimine zinc complex, stannous octanoate, dibutyltin dilaurate, bismuth octanoate, aluminum acetylacetonate, magnesium acetylacetonate, calcium acetylacetonate, 1,8-diazabicycloundec-7-ene, 4-dimethylaminopyridine, and 1,5,7-triazabicyclo[4.4.0]dec-5-ene.

[0021] The beneficial effects of adopting the above-mentioned improved scheme are as follows: the catalyst is selected from at least one of zinc oxide, zinc acetate, zinc octanoate, zinc isooctanoate, zinc trifluoromethanesulfonate, zinc L-carnosine, zinc acetylacetonate, β-diimine zinc complex, stannous octanoate, dibutyltin dilaurate, bismuth octanoate, aluminum acetylacetonate, magnesium acetylacetonate, calcium acetylacetonate, 1,8-diazabicycloundec-7-ene, 4-dimethylaminopyridine, and 1,5,7-triazabicyclo[4.4.0]dec-5-ene. The catalyst system covers metal salts, metal complexes, and organic base catalysts. Among them, zinc catalysts have both polymerization catalysis and zinc ion introduction functions, organic base catalysts have the characteristics of mild reaction conditions and high efficiency, and metal catalysts such as tin and bismuth provide diversified process options, which significantly broadens the applicability and flexibility of the preparation method.

[0022] The present invention provides a polylactic acid / nano zinc oxide hybrid material, wherein the hybrid material is prepared by the above-described preparation method, the hybrid material comprises zinc oxide and polylactic acid, and the zinc oxide and polylactic acid are connected by chemical bonds.

[0023] The technical effects of the L-polylactic acid / nano zinc oxide hybrid material provided by this invention are as follows: In the L-polylactic acid / nano zinc oxide hybrid material, zinc oxide and L-polylactic acid are connected by chemical bonds. This structural feature effectively avoids the physical migration and aggregation of nanoparticles in the polymer matrix, significantly improving the structural stability of the hybrid material during storage and use. The chemically bonded interface structure enhances the compatibility between the inorganic and organic phases, improves stress transfer efficiency, and thus enhances the mechanical strength and toughness of the material. This hybrid material combines the biodegradability of polylactic acid with the antibacterial and osteogenic activity of nano zinc oxide, providing comprehensive performance advantages for biomedical materials.

[0024] This invention provides applications of polylactic acid / nano zinc oxide hybrid materials, the biomedical implant materials including bone fixation materials, bone repair materials, cartilage repair materials, cosmetic implants, dental implant materials, oral restoration materials, and cardiovascular stent materials.

[0025] The technical effects of the L-polylactic acid / nano zinc oxide hybrid material provided by this invention are as follows: In the preparation of bio-implantable materials such as bone fixation materials, bone repair materials, cartilage repair materials, cosmetic implants, dental implant materials, oral prosthetic materials, and cardiovascular stent materials, this material utilizes its biodegradable properties to gradually degrade in vivo and be replaced by new tissue, avoiding the need for secondary surgical removal. The nano zinc oxide endows the material with broad-spectrum antibacterial properties, effectively reducing the risk of post-implantation infection. Simultaneously, the release of zinc ions promotes osteoblast proliferation and differentiation, accelerating bone tissue repair and integration, meeting the clinical needs of multiple fields such as hard tissue repair, soft tissue reconstruction, and vascular interventional therapy.

[0026] Compared with existing technologies, the beneficial effects of the L-polylactic acid / nano zinc oxide hybrid material, its preparation method, and its application provided by this invention are as follows: This invention employs a strategy of directly polymerizing L-lactide, nano zinc oxide, and a catalyst in bulk or in situ in a solvent. This fundamentally solves the inherent defect of insufficient interfacial compatibility in physical blending methods. During the polymerization process, the hydroxyl groups on the surface of the nano zinc oxide particles participate in the ring-opening reaction of lactide, forming a chemically bonded hybrid structure. This significantly enhances the interfacial bonding strength between the inorganic and organic phases, effectively avoiding the migration and aggregation of nanoparticles, and ensuring the structural stability of the material during storage and use. This method simultaneously achieves monomer polymerization and inorganic composite in a one-step reaction, greatly simplifying the process, reducing production costs, and improving batch reproducibility. After the reaction, the purification method of solvent dissolution and precipitant reprecipitation can efficiently remove residual catalysts and unreacted monomers, reducing the cytotoxicity of the material and ensuring biosafety. In the resulting hybrid material, nano-zinc oxide is chemically anchored to the polylactic acid (PLLA) molecular chain, enabling controlled and sustained release of zinc ions in a physiological environment. This provides sustained antibacterial activity, reducing the risk of implantation infection, while simultaneously promoting osteoblast proliferation and differentiation and inhibiting osteoclast activity through appropriate zinc ion concentration, synergistically accelerating bone repair. The chemically bonded interfacial structure optimizes stress transfer efficiency, improves the material's mechanical toughness and strength, and the uniform dispersion of nanoparticles effectively regulates the degradation rate of PLLA, mitigating the problem of acidic product release caused by autocatalysis, thus better matching the material's degradation process with tissue regeneration needs. This preparation method features mild process conditions and strong operational controllability, making it suitable for the molding and processing of various biomedical implant materials. It provides a comprehensive solution combining bioactivity, antibacterial function, and mechanical reliability for fields such as bone fixation materials, bone repair scaffolds, cartilage repair materials, cosmetic implants, dental implant materials, oral prosthetic materials, and cardiovascular stents. Attached Figure Description

[0027] Figure 1 This is a schematic diagram of the synthesis route of the L-polylactic acid / nano zinc oxide hybrid material in an embodiment of the present invention;

[0028] Figure 2 Tensile test curves of L-polylactic acid / nano zinc oxide hybrid material and L-polylactic acid material in Comparative Example 1 are shown.

[0029] Figure 3 Scanning electron microscope image of the tensile fracture surface of a polylactic acid / nano zinc oxide hybrid material;

[0030] Figure 4 This is a scanning electron microscope image of the tensile cross-section of the L-polylactic acid material in Comparative Example 1 of this invention;

[0031] Figure 5UV spectra of L-polylactic acid / nano zinc oxide hybrid material after one month in a standard buffer solution at pH 7.4 and standard buffer solution at pH 7.4 containing standard L-lactic acid sample.

[0032] Figure 6 UV spectra of polylactic acid / nano zinc oxide hybrid material after one month in a standard buffer solution at pH 7.0 and standard buffer solution at pH 7.0 containing standard sample polylactic acid.

[0033] Figure 7 The pH changes of the L-polylactic acid / nano zinc oxide hybrid material over time in standard buffer solutions at pH=7.4 and pH=7.0, respectively;

[0034] Figure 8 The pH changes of nano zinc oxide in Comparative Example 2 of this invention after being placed in standard buffer solutions at pH=7.4 and pH=7.0 for 2 days are shown. Detailed Implementation

[0035] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings.

[0036] The present invention provides a polylactic acid / nano zinc oxide hybrid material and its preparation method, comprising the following steps:

[0037] L-lactide, nano zinc oxide and catalyst are directly subjected to bulk polymerization or in situ polymerization in organic solvents to obtain the polymerization product.

[0038] The polymerization product was dissolved in an organic solvent and then reprecipitated in a precipitant to remove residual catalyst, thereby obtaining purified L-polylactic acid / nano zinc oxide hybrid material.

[0039] The specific embodiments of the present invention mainly include two process routes: bulk polymerization and solution in-situ polymerization. Both methods obtain L-polylactic acid / nano zinc oxide hybrid materials through polymerization reaction and purification treatment.

[0040] The bulk polymerization method is as follows: Under inert gas protection, L-lactide monomer and nano-zinc oxide are thoroughly premixed, and the nanoparticles are uniformly dispersed in the molten monomer by mechanical stirring or ultrasonic dispersion. Then, a catalyst is added, and the mixture is heated to above the melting point in a vacuum or closed system to initiate a ring-opening polymerization reaction. During the reaction, continuous stirring is maintained to ensure uniform mass transfer, and the molecular weight is adjusted by controlling the reaction time and temperature. After the reaction, the resulting hybrid material bulk is cooled to room temperature, pulverized into particles of appropriate size, and dissolved in an organic solvent to form a homogeneous solution. The solution is then added dropwise to a precipitant under continuous stirring, causing the polymer chains to redefine and precipitate, while residual catalyst and small molecule impurities remain in the liquid phase. After filtration, washing, and drying, the purified hybrid material is obtained.

[0041] The solution in-situ polymerization method is as follows: A reaction solution is prepared by dissolving L-lactide monomer in an organic solvent. Nano-zinc oxide is added to the solution, and the nanoparticles are monodispersed in the solution through ultrasonic treatment and mechanical stirring. Subsequently, a catalyst is added and mixed thoroughly. The mixture is then heated to a set temperature in a reflux or closed reactor to carry out the in-situ polymerization reaction. During this process, the solvent effectively reduces the viscosity of the system, promoting full contact between the monomer and the nanoparticles, allowing lactide to undergo ring-opening polymerization at the active sites on the surface of the zinc oxide nanoparticles, forming a chemically bonded hybrid structure. After the reaction is complete, the reaction solution is cooled to room temperature, and a precipitant is added dropwise under continuous stirring for reprecipitation. The morphology of the precipitated particles is controlled by adjusting the precipitant addition rate and stirring intensity. After solid-liquid separation, washing, and vacuum drying, the target product is obtained.

[0042] In both of the above embodiments, inert gas protection effectively prevents oxidative degradation of monomers and polymers; the solid-liquid ratio should be controlled during the dissolution process to ensure complete dissolution; the precipitant should be miscible with the solvent but insoluble in the polymer, and efficient purification can be achieved through rapid mixing; vacuum drying is used in the drying process to avoid polymer degradation caused by high temperatures. The entire process achieves chemical bonding and uniform dispersion of nano-zinc oxide in the polylactic acid matrix through coordinated control of reaction parameters.

[0043] In the above technical solution, the mass ratio of L-lactide, nano zinc oxide and catalyst is 5000:1~2:2~30.

[0044] Furthermore, in the above technical solution, when the polymerization reaction is in-situ polymerization, the mass ratio of L-lactide to the volume ratio of organic solvent is 1~2.5g:1~10mL.

[0045] Furthermore, in the above technical solution, the organic solvent is selected from at least one of dichloromethane, chloroform, toluene, ethyl acetate, acetone, and tetrahydrofuran.

[0046] Furthermore, in the above technical solution, the average particle size of nano zinc oxide is 5~100nm.

[0047] Furthermore, in the above technical solution, the reaction temperature of the polymerization reaction is 80~140℃.

[0048] Furthermore, in the above technical solution, the catalyst is selected from at least one of zinc oxide, zinc acetate, zinc octanoate, zinc isooctanoate, zinc trifluoromethanesulfonate, zinc L-carnosine, zinc acetylacetonate, β-diimine zinc complex, stannous octanoate, dibutyltin dilaurate, bismuth octanoate, aluminum acetylacetonate, magnesium acetylacetonate, calcium acetylacetonate, 1,8-diazabicycloundec-7-ene, 4-dimethylaminopyridine, and 1,5,7-triazabicyclo[4.4.0]dec-5-ene.

[0049] The present invention provides a polylactic acid / nano zinc oxide hybrid material, wherein the hybrid material comprises zinc oxide and polylactic acid, and the zinc oxide and polylactic acid are connected by chemical bonds.

[0050] Biomedical implant materials include bone fixation materials, bone repair materials, cartilage repair materials, cosmetic implants, dental implant materials, oral restoration materials, and cardiovascular stent materials.

[0051] Specifically, the principle of this invention is as follows: The core technology of this invention lies in utilizing the abundant hydroxyl active sites on the surface of nano-zinc oxide as co-initiators or chain transfer sites in the in-situ ring-opening polymerization process of lactide monomers. Under the action of a catalyst, the L-lactide monomer undergoes a ring-opening reaction on the surface of nano-zinc oxide and initiates chain growth. The polymerization active center undergoes chain transfer or termination reactions with the hydroxyl groups on the particle surface, causing the polylactic acid molecular chains to be chemically bonded to the surface of nano-zinc oxide through covalent bonds or strong coordination bonds, forming an inorganic-organic hybrid network structure. This chemically bonded interface significantly improves the compatibility between polylactic acid and zinc oxide, eliminates the interface defects and phase separation phenomena present in traditional physical blending, and allows the nanoparticles to exhibit a nanoscale uniform dispersion in the matrix, thereby fully utilizing the nano-reinforcing effect. From the perspective of degradation regulation mechanisms, chemically bonded nano-zinc oxide neutralizes localized acidic degradation products during the initial stage of PLLA hydrolysis by releasing zinc ions, buffering the pH drop and inhibiting the chain reaction of autocatalytic degradation, thus making the degradation rate gradual and controllable. As the material gradually degrades, zinc ions are continuously released and participate in physiological metabolism, exerting antibacterial and osteogenic regulatory functions. In terms of mechanical properties, the chemically bonded interface ensures effective stress transfer between the organic and inorganic phases, avoiding premature failure caused by interfacial debonding in traditional blends, and significantly improving the material's toughness, strength, and fatigue durability. In summary, this invention constructs a structurally stable and functionally synergistic hybrid system through an in-situ chemical bonding strategy, achieving a unity of material preparation and functional design at the molecular scale, providing a reliable technical path for developing next-generation intelligent responsive biomedical implant materials.

[0052] Example 1: See Figure 1 This is a schematic diagram of the synthesis route of L-polylactic acid / nano zinc oxide hybrid material. This embodiment includes a method for preparing L-polylactic acid with nano zinc oxide at the chain end, comprising the following steps:

[0053] 20g of L-lactide with a purity of 99.9% was melted in a pressure-resistant bottle at 90℃ to obtain a melt of the polymerized monomer;

[0054] Add 71.4 mg (0.171 mmol) of stannous isooctanoate to the melt, and add 5.6 mg of nano zinc oxide powder while stirring vigorously. At the same time, raise the temperature to 150 °C and react for 1.5 h after the reaction system temperature reaches the set temperature.

[0055] After the reaction system cooled to room temperature, sufficient dichloromethane was added to a pressure-resistant flask to dissolve the obtained polylactic acid. The polylactic acid solution was then slowly added dropwise to vigorously stirred ethanol to obtain medical-grade L-polylactic acid. The weight-average molecular weight of polylactic acid in the obtained L-polylactic acid / nano zinc oxide hybrid material was 36.1 × 10⁻⁶. The molecular weight distribution is 1.59.

[0056] Example 2: This example includes a method for preparing L-polylactic acid with nano-zinc oxide at the chain ends, comprising the following steps:

[0057] 20g of L-lactide with a purity of 99.9% was dissolved in 50mL of toluene solution at 100℃ to obtain a monomeric solution of toluene.

[0058] Add 29.7 mg (0.069 mmol) of stannous isooctanoate to the solution, and add 5.6 mg of nano zinc oxide powder while stirring vigorously. At the same time, raise the temperature to 110 °C and react for 24 h after the reaction system temperature reaches the set temperature.

[0059] After the reaction system cooled to room temperature, sufficient dichloromethane was added to a pressure-resistant flask to dissolve the obtained polylactic acid. The polylactic acid solution was then slowly added dropwise to vigorously stirred ethanol to obtain L-polylactic acid. The weight-average molecular weight of polylactic acid in the obtained L-polylactic acid / nano zinc oxide hybrid material was 45.6 × 10⁻⁶. The molecular weight distribution is 1.74.

[0060] Example 3: This example provides a method for preparing L-polylactic acid with nano-zinc oxide at the chain ends. The specific steps are the same as in Example 2, except that the amount of catalyst and the choice of solvent are different, as shown in Table 1.

[0061] Table 1

[0062] Example 4: This example includes a method for preparing L-polylactic acid with nano-zinc oxide at the chain ends, comprising the following steps:

[0063] 23.0 g of L-lactide with a purity of 99.0% was dissolved in 20 mL of dichloromethane at 25 °C to obtain a monomeric solution of dichloromethane.

[0064] Add 5.6 mg of nano zinc oxide powder to the solution and stir to make the zinc oxide powder evenly distributed in the solution. Then, add 1.4 g of DBU to the solution while stirring vigorously. After three hours, add acetic acid to terminate the reaction.

[0065] A small amount of deionized water was added to the L-polylactic acid (PLA) solution obtained from the reaction. After thorough stirring, the mixture was allowed to stand for 1 hour. After phase separation, the upper aqueous phase was removed, and the lower organic phase was thoroughly dried to remove the solvent, yielding L-PLA. The weight-average molecular weight of the PLA in the obtained L-PLA / nano-zinc oxide hybrid material was 5.04 × 10⁻⁴ m³ / h. The molecular weight distribution is 1.56.

[0066] Example 5: This example provides a method for preparing L-polylactic acid with nano-zinc oxide at the chain ends. The specific steps are the same as in Example 1, except that the monomer purity, catalyst dosage, polymerization temperature, and polymerization time are different, as shown in Table 2.

[0067] Table 2

[0068]

[0069] Example 6: This example provides a method for preparing L-polylactic acid with nano-zinc oxide at the chain ends. The specific steps are the same as in Example 2, except that the monomer purity and catalyst dosage are different, as shown in Table 3.

[0070] Table 3

[0071]

[0072] Example 7: This example provides a method for preparing L-polylactic acid with nano-zinc oxide at the chain ends. The specific steps are the same as in Example 2, except that the solvent is ethyl acetate, and the monomer purity, monomer amount, catalyst amount, and initiator amount are selected differently, as shown in Table 4.

[0073] Table 4

[0074]

[0075] Comparative Example 1: 50g of L-lactide with a purity of 99.9% was dissolved in 100mL of ethyl acetate solution at 100℃ to obtain a monomeric solution of ethyl acetate.

[0076] Add 83.4 mg of stannous isooctanoate to the solution, and add 18.6 mg of benzyl alcohol while stirring vigorously. At the same time, raise the temperature to 110°C and react for 24 hours after the reaction system reaches the set temperature.

[0077] After the reaction system cooled to room temperature, sufficient dichloromethane was added to a pressure-resistant flask to dissolve the obtained polylactic acid. The polylactic acid solution was then slowly added dropwise to vigorously stirred ethanol to obtain L-polylactic acid. The weight-average molecular weight of the obtained L-polylactic acid was 31.0 × 10⁻⁶. The molecular weight distribution is 1.40.

[0078] Depend on Figure 2 It can be seen that, among materials with similar molecular weights (the weight-average molecular weight of L-polylactic acid in the L-polylactic acid / nano zinc oxide hybrid material is 31.0 × 10⁻⁶), The weight-average molecular weight of L-polylactic acid without zinc oxide is 33.5 × Under the conditions described, the mechanical properties of the L-polylactic acid / nano zinc oxide hybrid material obtained by ring-opening polymerization of L-lactide initiated by nano zinc oxide were slightly improved compared with those of L-polylactic acid obtained by ring-opening polymerization of L-lactide initiated by benzyl alcohol. Young's modulus increased from 101.7 MPa to 108.8 MPa; tensile strength increased from 57.6 MPa to 58.2 MPa; and elongation at break increased from 78.2% to 88.0%. This indicates that the chemical bonding of L-polylactic acid with nano zinc oxide does not lead to a decrease in the mechanical properties of L-polylactic acid, but rather has a certain improving effect.

[0079] Depend on Figure 3 It can be seen that nano-zinc oxide did not aggregate in the L-polylactic acid / nano-zinc oxide hybrid material. Figure 3 and Figure 4 The comparison shows that, under similar molecular weight conditions, the L-lactic acid / nano zinc oxide hybrid material obtained by ring-opening polymerization of L-lactide initiated by benzyl alcohol has more fracture surface textures and better fracture toughness than L-lactic acid obtained by ring-opening polymerization of L-lactide initiated by nano zinc oxide.

[0080] Depend on Figure 5 and Figure 6 It can be seen that the L-polylactic acid / nano zinc oxide hybrid material underwent L-polylactic acid degradation in both standard buffer solutions at pH 7.4 and pH 7.0, generating L-lactic acid (LLA), and the degradation rate was faster under alkaline conditions at pH 7.4.

[0081] Example 8: A small piece of the prepared polylactic acid / nano zinc oxide hybrid material was taken and added to 10 mL of standard buffer solutions with pH=7.4 and pH=7.0. The solutions were shaken in a 37°C water bath. The standard buffer solutions were changed every two days. The pH value of the extract after soaking for different days was measured with a pH meter. The solution was changed 24 hours before degradation, and the measurement results were the degradation effect within 24 hours. The presence of the degradation product polylactic acid in the extract after soaking for 30 days was measured with UV-Vis spectroscopy and compared with the standard substance polylactic acid.

[0082] Depend on Figure 7 The pH change curves show that the L-polylactic acid / nano zinc oxide hybrid material obtained by the ring-opening polymerization of L-lactide initiated by nano zinc oxide tends to stabilize the pH of the solution in standard buffer solutions at pH 7.4 and pH 7.0. This is because the lactic acid produced by the degradation of L-polylactic acid causes the pH to decrease, but the lactic acid can be neutralized by the zinc oxide released from the degradation, thus stabilizing the pH of the solution.

[0083] Comparative Example 2: 10 mg of nano zinc oxide was added to 10 mL of standard buffer solutions with pH=7.4 and pH=7.0 respectively, and the pH value of the extract was measured with a pH meter after soaking for two days.

[0084] Depend on Figure 8 It can be seen that when nano zinc oxide is placed in standard buffer solutions at pH 7.4 and pH 7.0 and shaken in a water bath at 37°C, the pH values ​​increase to 10.34 and 7.24 respectively after 2 days, further verifying that nano zinc oxide has the ability to neutralize acidic substances and prevent the pH value from decreasing.

[0085] The above description is merely a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any changes or substitutions that can be easily conceived by those skilled in the art within the scope of the technology disclosed in the present invention should be included within the scope of protection of the present invention.

Claims

1. A method for preparing a polylactic acid / nano zinc oxide hybrid material, characterized in that, Includes the following steps: L-lactide, nano zinc oxide and catalyst are directly subjected to bulk polymerization or in situ polymerization in organic solvents to obtain the polymerization product. The polymerization product is dissolved in an organic solvent and then reprecipitated in a precipitant to remove residual catalyst, thereby obtaining purified L-polylactic acid / nano zinc oxide hybrid material. The catalyst is selected from at least one of zinc oxide, zinc acetate, zinc octanoate, zinc isooctanoate, zinc trifluoromethanesulfonate, zinc L-carnosine, zinc acetylacetonate, zinc β-diimine complex, stannous octanoate, dibutyltin dilaurate, bismuth octanoate, aluminum acetylacetonate, magnesium acetylacetonate, calcium acetylacetonate, 1,8-diazabicycloundec-7-ene, 4-dimethylaminopyridine, and 1,5,7-triazabicyclo[4.4.0]dec-5-ene.

2. The method for preparing a polylactic acid / nano zinc oxide hybrid material according to claim 1, characterized in that, The mass ratio of L-lactide, nano zinc oxide, and catalyst is 5000:1~2:2~30.

3. The method for preparing a polylactic acid / nano zinc oxide hybrid material according to claim 2, characterized in that, When the polymerization reaction is in situ polymerization, the mass ratio of the L-lactide to the volume of the organic solvent is 1~2.5g:1~10mL.

4. The method for preparing a polylactic acid / nano zinc oxide hybrid material according to claim 3, characterized in that, The organic solvent is selected from at least one of dichloromethane, chloroform, toluene, ethyl acetate, acetone, and tetrahydrofuran.

5. The method for preparing a polylactic acid / nano zinc oxide hybrid material according to claim 4, characterized in that, The average particle size of the nano-zinc oxide is 5~100nm.

6. The method for preparing a L-polylactic acid / nano zinc oxide hybrid material according to claim 5, characterized in that, The polymerization reaction temperature is 80~140℃.

7. A L-polylactic acid / nano zinc oxide hybrid material, characterized in that, The hybrid material is prepared by any one of claims 1 to 6, wherein the hybrid material comprises zinc oxide and polylactic acid (PLA), and the zinc oxide and PLA are connected by chemical bonds.

8. Application of L-polylactic acid / nano zinc oxide hybrid materials, characterized in that, This includes the application of the L-polylactic acid / nano zinc oxide hybrid material as described in claim 7 in biomedical implant materials, which include bone fixation materials, bone repair materials, cosmetic implants, dental implant materials, oral restoration materials, and cardiovascular stent materials.

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