Degradable non-woven fabric and preparation process thereof

Abstract

The invention relates to the technical field of biomedical materials, and discloses a degradable non-woven fabric and a preparation process thereof, the non-woven fabric is prepared from polylactic acid, polycaprolactone, periodate, a copolyester oligomer containing a cis-1, 2-cyclohexanediol structural unit, and a solid biocompatible weakly alkaline salt; the preparation process comprises the following steps: mixing the components, and performing melt blending and melt-blowing spinning to prepare the non-woven fabric. The periodate and the copolyester oligomer are used as latent reaction precursors, the alkalescent salt is used as a pH regulating agent, when the non-woven fabric is in contact with an aqueous environment, the alkalescent salt is dissolved out to establish an alkalescent microenvironment, the periodate is promoted to carry out oxidative cracking on the copolyester oligomer, and thus the aldehyde compound with antibacterial activity is generated in situ. According to the invention, the on-demand generation of antibacterial substances is realized, so that the non-woven fabric has high antibacterial rate and low cytotoxicity, and the technical problem that the activity and safety of a traditional antibacterial material are difficult to balance is solved.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biomedical materials, in particular to a degradable non-woven fabric and a preparation process thereof. BACKGROUND

[0002] Degradable polymer materials, such as polylactic acid (PLA) and polycaprolactone (PCL), are widely used in the preparation of non-woven fabrics due to their good biocompatibility and degradability, and are used as medical products such as wound dressings and tissue engineering scaffolds. In these applications, the antibacterial performance of the material is crucial to prevent bacterial infection.

[0003] Currently, the technical approach to achieving antibacterial function of degradable non-woven fabric is usually to directly add or blend antibacterial agents in the polymer matrix. These antibacterial agents include silver ions, quaternary ammonium salts, triclosan and other substances. This method relies on the migration and release of antibacterial agents from the material matrix to the surface of the material or the surrounding environment to inhibit or kill microorganisms through direct contact. However, this technical approach has inherent technical defects. The added antibacterial agents, while exerting antibacterial effects, may also release components that are toxic to human tissue cells, thereby affecting the normal repair and regeneration of tissues, leading to a contradiction between the antibacterial effectiveness and biocompatibility of the material.

[0004] In addition, the release process of the antibacterial agent is usually difficult to accurately control, often showing an initial burst release of a large amount and a rapid decay in the later period. The initial high concentration can exacerbate the risk of cytotoxicity, while the insufficient concentration in the later period can lead to ineffective antibacterial effect, and even induce bacterial resistance. At the same time, some antibacterial agents may decompose or become inactive under high-temperature processing conditions such as melt spinning of the material, which not only reduces the final antibacterial performance of the product, but also may introduce uncertain degradation products, affecting the safety of the material. Therefore, there is still an urgent need for a degradable non-woven fabric that can provide stable and effective antibacterial function while ensuring biological safety. SUMMARY

[0005] The technical problem to be solved by the present application is that the existing degradable materials with antibacterial function obtained by directly adding antibacterial agents generally have the technical contradiction that antibacterial activity and biocompatibility are difficult to balance.

[0006] To solve the above problems, the present application provides the following technical solutions:

[0007] In a first aspect, the present application provides a degradable non-woven fabric, which adopts the following technical solutions:

[0008] A degradable non-woven fabric is made of components containing the following weight parts:

[0009] Polylactic acid: 58-68 parts;

[0010] Polycaprolactone: 25-29 parts;

[0011] Periodate: 1-5 parts;

[0012] Copolyester oligomer containing cis-1,2-cyclohexanediol structural units: 2-8 parts;

[0013] Solid-state biocompatible weakly basic salt: 1-3 parts.

[0014] By adopting the above technical scheme, the periodate as a latent precursor, the copolyester oligomer containing cis-1,2-cyclohexanediol structural units, and the solid-state biocompatible weakly basic salt as a pH regulator and catalyst are physically coated and immobilized in the degradable polymer matrix composed of polylactic acid and polycaprolactone through a melt blending process, thereby effectively isolating the highly active reactants from the external biological environment. When the non-woven fabric contacts with the aqueous environment, a series of slow, controllable and microcosmic synergistic chemical reactions occur on the surface of the fiber material:

[0015] Firstly, the solid-state biocompatible weakly basic salt is dissolved and hydrolyzed from the polymer matrix, temporarily adjusting the local microenvironment pH value on the surface of the material fiber to weakly basic, as a key catalytic condition to start the subsequent oxidative cleavage reaction.

[0016] Then, under the above weakly basic condition, the periodate performs oxidative cleavage reaction on the cis-1,2-cyclohexanediol structural units on the molecular chain of the copolyester oligomer.

[0017] Finally, the oxidative cleavage reaction breaks the carbon-carbon single bond on the cis-1,2-cyclohexanediol structural units and generates two aldehyde groups in situ at the breaking point, thereby generating and releasing aldehyde compounds with antibacterial activity in situ in the non-woven fabric.

[0018] The technical scheme realizes the on-demand and in-situ generation of antibacterial active substances by constructing a latent reaction system composed of two inert precursors and a pH regulator in the polymer matrix. The system ingeniously uses the wound exudate as a natural reaction trigger signal, making the generation rate of the antibacterial substance positively related to the wetness of the wound surface (i.e. the infection or inflammation state), thereby realizing the on-demand response and intelligent regulation of antibacterial activity. This design not only avoids the biological toxicity that may be caused by directly adding high-concentration active antibacterial agents, but also automatically reduces the reaction rate as the exudate decreases in the later healing period, avoiding potential toxicity to the newly formed tissue. At the same time, the local and temporary weakly basic environment created by the pH regulator improves the rate and efficiency of the in-situ chemical reaction, enabling the non-woven fabric to exhibit low cytotoxicity while achieving high antibacterial rate.

[0019] Preferably, the non-woven fabric is made of components including the following weight parts: polylactic acid 60-65 parts; polycaprolactone 25-30 parts; periodate 2-4 parts; copolyester oligomer containing cis-1,2-cyclohexanediol structural units 4-6 parts; and solid biocompatible weakly basic salt 1.5-2.5 parts.

[0020] By adopting the above technical solution, the ratio of each component is further optimized. This ratio range ensures the processing flowability in the melt spinning process, while enabling the non-woven fabric to generate sufficient concentration of aldehyde substances after contacting the aqueous environment, to achieve an antibacterial rate higher than 99.9%, and maintain a cytotoxicity level of Grade 1.

[0021] Preferably, the copolyester oligomer containing cis-1,2-cyclohexanediol structural units is prepared by polycondensation reaction of cis-1,2-cyclohexanediol and adipic acid, and has a number average molecular weight of 1500-5000 g / mol.

[0022] By adopting the above technical solution, the source and molecular weight of the copolyester oligomer as the reaction substrate are limited. This molecular weight range ensures that the oligomer is in a solid state at room temperature, easy to mix with other powder components and disperse in the polymer matrix, while ensuring that each molecular chain contains sufficient reaction sites (cis-1,2-cyclohexanediol units) and does not affect the melt processing performance of the material due to excessively high molecular weight.

[0023] Preferably, the solid biocompatible weakly basic salt is arginine bicarbonate and / or trisodium citrate.

[0024] By adopting the above technical solution, the specific substance of the pH regulator is specified. Arginine bicarbonate and trisodium citrate are both solid salts with biocompatibility, which can stably provide a weakly basic buffer system in an aqueous environment.

[0025] Preferably, the periodate is potassium periodate.

[0026] By adopting the above technical solution, the specific substance of the oxidizing agent is specified. Potassium periodate is a stable and easily accessible solid oxidizing agent with thermal stability at melt processing temperature, which can effectively oxidize 1,2-diol in an aqueous environment.

[0027] In a second aspect, the present application provides a process for preparing the above-mentioned degradable non-woven fabric, adopting the following technical solution:

[0028] A process for preparing a degradable non-woven fabric, comprising the following steps:

[0029] Mixing polylactic acid, polycaprolactone, periodate, a copolyester oligomer containing cis-1,2-cyclohexanediol structural units, and a solid biocompatible weak base salt to obtain a mixture;

[0030] Melt blending and melt blowing and spinning the mixture to obtain superfine fibers;

[0031] Collecting the superfine fibers into a net to obtain a non-woven fabric.

[0032] By adopting the above technical solution, the reaction components are uniformly coated and dispersed in the fiber matrix composed of polylactic acid and polycaprolactone in a dry state by using the waterless processing technology of melt blending and melt blowing and spinning. Since water is needed as a medium for in-situ chemical reaction, no chemical reaction occurs between the components during the entire high-temperature melt processing, thereby achieving the goal of stably immobilizing the complete latent chemical reaction system inside the non-woven fabric fibers. The process flow is simple and suitable for large-scale industrial production.

[0033] Preferably, before mixing, a step of ball milling the periodate is further included.

[0034] By adopting the above technical solution, the particle size of the periodate is reduced by pretreatment, which can make it more uniformly dispersed in the polymer melt in the subsequent melt blending step, thereby ensuring that the internal reaction site distribution of the final obtained fiber is uniform, and the overall antibacterial performance of the non-woven fabric is stable.

[0035] Preferably, in the step of melt blending and melt blowing and spinning, the melt temperature is 195-215℃, and the hot air temperature is 200-230℃.

[0036] By adopting the above technical solution, the key process temperature range is limited. This temperature range not only ensures the sufficient plasticization and low viscosity of polylactic acid and polycaprolactone to facilitate the formation of superfine fibers, but also avoids the thermal degradation of the polymer matrix or functional additives due to excessively high temperature.

[0037] Preferably, after collecting into a net, a step of heat pressing the non-woven fabric is further included, and the heat pressing temperature is 95-110℃.

[0038] By adopting the above technical solution, the heat pressing treatment increases the bonding points between the fibers, improves the mechanical strength and structural compactness of the non-woven fabric, and makes it more suitable for practical application.

[0039] In summary, the present application includes at least one of the following beneficial technical effects:

[0040] 1. The degradable nonwoven fabric of the present application immobilizes the periodate salt as a chemical precursor and the copolyester oligomer in an inert state in the polymer matrix. The antibacterial active substance is not directly added, but is generated on demand by in-situ chemical reaction between the precursors after the nonwoven fabric contacts with the aqueous environment. This design avoids the direct addition of free high-activity antibacterial agents in the material, so that the material exhibits high antibacterial rate while the in-vitro cytotoxicity grade of its leaching solution is grade 1, solving the technical problem that the antibacterial performance and biocompatibility of the material are difficult to be balanced in the prior art.

[0041] 2. The degradable nonwoven fabric of the present application introduces a solid-state biocompatible weakly basic salt in the composition. This component can adjust the microenvironment around the material to weakly basic when it contacts with the aqueous environment, and this pH condition can effectively accelerate the oxidative cleavage reaction of the periodate salt on the copolyester oligomer. Test results show that the generation rate and final antibacterial rate of the antibacterial active substance of the material containing this component are significantly higher than those of the system without this component, confirming the catalytic function of this component on the in-situ chemical reaction, and through the synergistic effect of the components in the system, the effective realization of the antibacterial function of the material is ensured.

[0042] 3. The preparation process of the present application uses melt blending and melt blowing spinning technology. Since water is needed as a medium to trigger the in-situ chemical reaction, during the entire water-free high-temperature melt processing process, the reaction components can be uniformly dispersed and coated in the polymer fibers in a chemically inert state. This process ensures the stability of the latent reaction system during preparation and storage, and can prepare nonwoven fabric products with uniform performance and controllable triggered antibacterial function through mature industrialized methods. DETAILED DESCRIPTION

[0043] The sources and specifications of the main raw materials and reagents used in the following examples and comparative examples are as follows, and the reagents not specifically explained are commercially available analytical pure or higher grade products.

[0044] Polylactic acid (PLA), CAS number: 26100-51-6, the weight average molecular weight of the PLA used in the examples of the present application ranges from 150000 to 250000 g / mol.

[0045] Polycaprolactone (PCL), CAS number: 24980-41-4, the weight average molecular weight of the PCL used in the examples of the present application ranges from 70000 to 100000 g / mol.

[0046] 1,2-cyclohexanediol-adipic acid copolyester oligomer, which is a self-made material of the present application, its specific preparation method is described in the following preparation examples. The material is a linear copolyester oligomer prepared from cis-1,2-cyclohexanediol (CAS No.: 1792-81-0) and adipic acid (CAS No.: 124-04-9) through polycondensation reaction, and its chemical structure contains adjacent diol structure units derived from cis-1,2-cyclohexanediol and adipate structure units derived from adipic acid. The oligomer is a brittle solid at room temperature (25°C) and is colorless to light yellow, and its number average molecular weight ranges from 1500 to 5000 g / mol.

[0047] Preparation Examples 1-2:

[0048] Preparation Example 1:

[0049] The present preparation example provides a preparation method of 1,2-cyclohexanediol-adipic acid copolyester oligomer (B-1), which comprises the following steps:

[0050] 1) In a 1000 mL three-necked flask equipped with a mechanical stirring device, a thermometer, a nitrogen protection pipe and a Dean-Stark water separator, adipic acid 146.14 g (1.0 mol), cis-1,2-cyclohexanediol 127.78 g (1.1 mol), p-toluenesulfonic acid monohydrate 1.4 g as a catalyst, and 400 mL of toluene as a water-carrying agent were added.

[0051] 2) Turn on the mechanical stirring (200 rpm) and introduce nitrogen to replace the air in the system. Heat the reaction mixture to 150°C and maintain this temperature to make toluene reflux. The water generated during the reaction forms an azeotrope with toluene, which is separated in the water separator and collected after condensation. Continue the reaction for 8 hours, and when the amount of water collected approaches the theoretical value (1.0 mol, about 18 mL), stop heating and naturally cool the reaction system to room temperature.

[0052] 3) Transfer the reaction product to a rotary evaporator and evaporate the toluene under the conditions of a 65°C water bath and vacuum. Dissolve the obtained viscous liquid in 500 mL of dichloromethane, wash with 200 mL of saturated sodium bicarbonate aqueous solution twice, and then wash with 200 mL of deionized water until neutral. Separate the organic phase and dry it with anhydrous magnesium sulfate for 12 hours.

[0053] 4) After removing the drying agent by filtration, remove most of the dichloromethane from the filtrate by rotary evaporation, and finally place it in a 70°C vacuum drying oven for 36 hours to constant weight to obtain the product B-1.

[0054] The product B-1 is a light yellow brittle solid. Its number average molecular weight is 2150 g / mol and its polydispersity index is 1.62, as determined by gel permeation chromatography (GPC, tetrahydrofuran as mobile phase, polystyrene as standard).

[0055] Preparation Example 2:

[0056] This preparation example provides a method for preparing 1,2-cyclohexanediol-adipic acid copolyester oligomer (B-2), as follows:

[0057] The basic operation steps are the same as those in Preparation Example 1. The difference is that the feeding amount of the raw materials is as follows: adipic acid 146.14 g (1.0 mol), cis-1,2-cyclohexanediol 121.97 g (1.05 mol). The reaction time is extended to 10 hours to obtain a higher degree of polymerization.

[0058] The finally obtained product B-2 is a light yellow brittle solid. Its number average molecular weight is 4680 g / mol and its polydispersity index is 1.85, as determined by gel permeation chromatography (GPC, tetrahydrofuran as mobile phase, polystyrene as standard).

[0059] Examples 1-4:

[0060] Example 1: This example provides a preparation process of a degradable non-woven fabric, comprising the following steps:

[0061] 1. Raw material preparation and mixing:

[0062] According to the weight fraction, the following components are weighed: polylactic acid (PLA) 63 parts, polycaprolactone (PCL) 27 parts, ball-milled potassium periodate 3 parts, 1,2-cyclohexanediol-adipic acid copolyester oligomer (B-1) prepared in Preparation Example 1 5 parts, and arginine bicarbonate 2 parts.

[0063] The weighed PLA and PCL particles are dried in a vacuum drying oven at 80°C for 10 hours; the potassium periodate, oligomer B-1 and arginine bicarbonate are dried in a vacuum drying oven at 70°C for 5 hours.

[0064] All the dried materials are placed in a high-speed mixer and mixed at room temperature for 15 minutes to uniformly disperse the components.

[0065] 2. Melt blending and melt-blowing spinning:

[0066] The above mixture is uniformly fed into a co-rotating twin-screw extruder through a loss weight feeder. The temperature of each zone of the extruder is set as follows: feeding zone 170°C, compression zone 190°C, metering zone and die 200°C. The screw rotation speed is set to 150 rpm.

[0067] The melt is plasticized and uniformly mixed in the extruder, and then enters the melt-blowing die. The melt-blowing process parameters are set as follows: melt temperature 205°C, hot air temperature 215°C, hot air pressure 0.3 MPa, and receiving distance 30 cm. The melt stream is drawn into ultrafine fibers by high-speed hot air.

[0068] 3. Web formation and post-processing:

[0069] The ultrafine fibers are collected on a web curtain under negative pressure suction, and form a uniform nonwoven fabric web after cooling.

[0070] The web is subjected to calendering treatment by hot calender rollers with a linear pressure of 3 MPa and a temperature of 95°C, so as to increase the surface flatness and mechanical strength thereof.

[0071] The prepared nonwoven fabric is cut, sealed and packaged, and then subjected to final sterilization by using ethylene oxide, so as to obtain a finished product.

[0072] Example 2: This example provides a preparation process of a degradable nonwoven fabric, which comprises the following steps:

[0073] 1. Raw material preparation and mixing:

[0074] The following components are weighed according to the weight fraction: polylactic acid (PLA) 67.2 parts, polycaprolactone (PCL) 28.8 parts, ball-milled high-potassium periodate 1 part, 1,2-cyclohexanediol-adipic acid copolyester oligomer (B-1) prepared in Preparation Example 1 2 parts, and arginine bicarbonate 1 part.

[0075] The weighed PLA and PCL particles are dried in a vacuum drying oven at 80°C for 12 hours; the high-potassium periodate, the oligomer B-1 and the arginine bicarbonate are dried in a vacuum drying oven at 70°C for 6 hours.

[0076] All the dried materials are placed in a high-speed mixer and mixed at room temperature for 20 minutes, so as to uniformly disperse the components.

[0077] 2. Melt blending and melt-blowing spinning:

[0078] The above mixed materials are uniformly fed into a co-rotating twin-screw extruder through a loss-in-weight feeder. The temperature of each zone of the extruder is set as follows: feeding zone 160°C, compression zone 180°C, metering zone and die 190°C. The screw rotation speed is set as 100 rpm.

[0079] The melt is plasticized and uniformly mixed in the extruder, and then enters the melt-blowing die. The melt-blowing process parameters are set as follows: melt temperature 195°C, hot air temperature 200°C, hot air pressure 0.2 MPa, and receiving distance 40 cm. The melt stream is drawn into ultrafine fibers by high-speed hot air.

[0080] 3. Web formation and post-processing:

[0081] The ultrafine fibers are collected on a web curtain under negative pressure suction, and form a uniform nonwoven fabric web after cooling.

[0082] The prepared nonwoven fabric is cut, sealed and packaged, and finally sterilized by cobalt-60 irradiation (dose 25 kGy) to obtain a finished product.

[0083] Example 3: This example provides a preparation process of a degradable nonwoven fabric, comprising the following steps:

[0084] 1. Raw material preparation and mixing:

[0085] According to the weight fraction, the following components are weighed: polylactic acid (PLA) 58.8 parts, polycaprolactone (PCL) 25.2 parts, ball-milled potassium periodate 5 parts, 1,2-cyclohexanediol-adipic acid copolymer oligomer (B-1) prepared in Preparation Example 1 8 parts, and arginine bicarbonate 3 parts.

[0086] The weighed PLA and PCL particles are dried in a vacuum drying oven at 90°C for 8 hours; the potassium periodate, oligomer B-1 and arginine bicarbonate are dried in a vacuum drying oven at 80°C for 4 hours.

[0087] All the dried materials are placed in a high-speed mixer and mixed at room temperature for 10 minutes to uniformly disperse the components.

[0088] 2. Melt blending and melt blowing spinning:

[0089] The above mixture is uniformly fed into a co-rotating twin-screw extruder through a loss-in-weight feeder. The temperature of each zone of the extruder is set as follows: feeding zone 180°C, compression zone 200°C, metering zone and die 210°C. The screw rotation speed is set to 200 rpm.

[0090] After the melt is plasticized and uniformly mixed in the extruder, it enters the melt-blowing die. The melt-blowing process parameters are set as follows: melt temperature 215°C, hot air temperature 230°C, hot air pressure 0.4 MPa, and receiving distance 20 cm. The melt stream is drawn into ultrafine fibers by high-speed hot air.

[0091] 3. Web formation and post-treatment:

[0092] The ultrafine fibers are collected on a web curtain under negative pressure suction, and form a uniform nonwoven fabric web after cooling.

[0093] The web is subjected to calendering treatment by hot calender rollers with a linear pressure of 5 MPa and a temperature of 110°C.

[0094] The prepared nonwoven fabric is cut, sealed and packaged, and finally sterilized by ethylene oxide to obtain a finished product.

[0095] Example 4: This example provides a preparation process of a degradable nonwoven fabric, comprising the following steps:

[0096] 1. Raw material preparation and mixing:

[0097] The following components were weighed according to the weight fraction: polylactic acid (PLA) 63 parts, polycaprolactone (PCL) 27 parts, ball-milled potassium periodate 3 parts, 1,2-cyclohexanediol-adipic acid copolyester oligomer (B-2) prepared in Preparation Example 2 5 parts, and trisodium citrate 2 parts.

[0098] The drying step of each component was the same as in Example 1.

[0099] All the dried materials were placed in a high-speed mixer and mixed at room temperature for 15 minutes to uniformly disperse each component.

[0100] 2. Melt blending and melt-blow spinning:

[0101] The process steps and parameters were the same as in Example 1. That is, the mixed material was fed into an extruder (temperature setting: 170 / 190 / 200°C; screw rotation speed: 150 rpm), and then passed through a melt-blow system (parameter setting: melt temperature 205°C, hot air temperature 215°C, hot air pressure 0.3 MPa, receiving distance 30 cm) to prepare ultrafine fibers.

[0102] 3. Webbing and post-processing:

[0103] The process steps and parameters were the same as in Example 1. That is, after webbing the fibers, hot pressing was performed (95°C, 3 MPa), and finally cutting, packaging and sterilization were performed to obtain the finished product.

[0104] Comparative Examples 1-5:

[0105] Comparative Example 1:

[0106] Compared with Example 1, the difference is that the formula of this comparative example does not contain potassium periodate, 1,2-cyclohexanediol-adipic acid copolyester oligomer (B-1), and arginine bicarbonate. Its formula is composed of polylactic acid (PLA) 70 parts and polycaprolactone (PCL) 30 parts, and the rest of the preparation process and parameters are the same as in Example 1.

[0107] Comparative Example 2:

[0108] Compared with Example 1, the difference is that the formula of this comparative example does not contain arginine bicarbonate as a pH regulator and catalyst. Its formula is composed of polylactic acid (PLA) 63 parts, polycaprolactone (PCL) 27 parts, potassium periodate 3 parts, and 1,2-cyclohexanediol-adipic acid copolyester oligomer (B-1) 5 parts, and the rest of the preparation process and parameters are the same as in Example 1.

[0109] Comparative Example 3:

[0110] Comparative Example 3 is different from Example 1 in that the formulation of Comparative Example 3 does not contain 1,2-cyclohexanediol-adipic acid copolyester oligomer (B-1) as a reaction substrate. Its formulation consists of polylactic acid (PLA) 63 parts, polycaprolactone (PCL) 27 parts, potassium periodate 3 parts, and arginine bicarbonate 2 parts, and the rest of the preparation process and parameters are the same as Example 1.

[0111] Comparative Example 4:

[0112] Comparative Example 4 is different from Example 1 in that the formulation of Comparative Example 4 does not contain potassium periodate as a latent oxidant. Its formulation consists of polylactic acid (PLA) 63 parts, polycaprolactone (PCL) 27 parts, 1,2-cyclohexanediol-adipic acid copolyester oligomer (B-1) 5 parts, and arginine bicarbonate 2 parts, and the rest of the preparation process and parameters are the same as Example 1.

[0113] Comparative Example 5:

[0114] Comparative Example 5 is different from Example 1 in that it uses a conventional antibacterial agent in the prior art to replace the self-activated antibacterial system of the present application. Its formulation does not contain potassium periodate, 1,2-cyclohexanediol-adipic acid copolyester oligomer (B-1), and arginine bicarbonate, but 1 part of polyhexamethylene biguanide (PHMB) is additionally added during the melt blending stage, and the rest of the preparation process and parameters are the same as Example 1.

[0115] Test Examples 1-4:

[0116] Test Example 1:

[0117] The purpose of this test example is to verify the function of the degradable non-woven fabric prepared in the embodiment of the present application to adjust the pH value of the environment to the weak alkaline range in an acidic aqueous solution environment.

[0118] The experimental steps are as follows:

[0119] 1. Solution preparation: Use potassium dihydrogen phosphate and sodium hydrogen phosphate to prepare a phosphate buffered saline solution (PBS) with a concentration of 0.1 mol / L, and use phosphoric acid to adjust its initial pH value to 5.5±0.1 to simulate an acidic microenvironment.

[0120] 2. Sample processing: Take the non-woven fabric prepared in Example 1, Comparative Example 1 and Comparative Example 2, respectively, and cut them into square samples with a mass of 1.0 g under sterile conditions.

[0121] 3. Soaking experiment: Each of the above samples was placed in a sterile beaker containing 20 mL of the above PBS solution at pH 5.5, ensuring complete submersion of the sample. The beaker was sealed with parafilm and placed in a constant temperature environment at 37°C.

[0122] 4. pH measurement: At five time points, 0 hour, 1 hour, 4 hours, 8 hours and 24 hours after the start of the soaking, the pH of the solution in each beaker was measured using a pH meter calibrated at three points (pH 4.01, 7.00, 10.01). Three parallel samples were set up for each sample group, and the results were averaged.

[0123] The data of the pH of each sample in the pH 5.5 buffer solution over time is recorded in Table 1 below.

[0124] Table 1: pH of each sample in the pH 5.5 buffer solution over time data:

[0125] The test data in Table 1 shows that the non-woven sample of Example 1, after being immersed in an acidic buffer solution with an initial pH of 5.51, the pH of the solution rapidly rises to 7.38 within 1 hour, and continues to rise in the subsequent time, and stabilizes at 8.11 after 24 hours. In contrast, the non-woven samples of Comparative Example 1 (blank substrate) and Comparative Example 2 (lack of pH control and catalyst) do not show significant changes in the pH of the solution during the entire 24-hour test period, and remain in the range of 5.5 to 5.7.

[0126] The above results are attributed to the presence of arginine bicarbonate in the composition of Example 1. When the non-woven is in contact with the aqueous solution, the solid weakly basic salt component is dissolved from the polymer matrix into the solution. The bicarbonate ions (HCO3 - ) produced by its hydrolysis react with hydrogen ions (H + ) in the solution, while the functional groups of the arginine molecules themselves participate in proton balance, together consuming the acidic substances in the solution. This process converts the acidic environment into a weakly basic buffer environment composed of arginine and carbonate systems.

[0127] The test results of Comparative Example 1 and Comparative Example 2 confirm that the matrix material composed of polylactic acid and polycaprolactone, potassium periodate and 1,2-cyclohexanediol-adipic acid copolyester oligomer itself does not have the function of adjusting the pH of the solution. Therefore, this test clearly shows that the addition of a solid biocompatible weakly basic salt in the non-woven fabric of the present invention gives the material the functional property of actively adjusting the acidic pH environment to a weakly basic state when it is in contact with an aqueous environment, which is the result of the synergistic effect of the inherent components of the material.

[0128] Test Example 2:

[0129] The present test example aims to quantitatively verify that the degradable non-woven fabric prepared in the embodiment of the present application can generate and release aldehyde compounds in situ through chemical reaction of its internal components after contacting with an aqueous solution.

[0130] The experimental steps are as follows:

[0131] 1. Preparation of standard solution and reagent:

[0132] A hexanedial standard was weighed and used to prepare a series of standard working solutions with concentration gradients (0, 5, 10, 15, 20, 25 μg / mL) using simulated body fluid (SBF).

[0133] An MBTH (3-methyl-2-benzothiazolinone hydrazone hydrochloride) detection reagent was prepared, which is used to react with aldehyde compounds and develop color.

[0134] 2. Sample extraction:

[0135] 1.0 g of each sample of the non-woven fabric prepared in Example 1, Comparative Example 2, Comparative Example 3 and Comparative Example 4 was weighed under sterile conditions.

[0136] Each sample was placed in a sterile container containing 20 mL of SBF solution, sealed and placed in a constant temperature environment at 37°C for extraction.

[0137] 3. Sample collection and detection:

[0138] 1.0 mL of the extraction solution was taken from each container at 4 hours, 8 hours and 24 hours after the start of extraction.

[0139] The extracted extraction solution was added with the MBTH detection reagent, and the color development reaction was carried out according to the standard colorimetric method procedure.

[0140] The absorbance of the solution after reaction was measured at a wavelength of 650 nm using a UV-visible spectrophotometer.

[0141] 4. Concentration calculation:

[0142] The same operation as step 3 was performed on the hexanedial standard working solution to measure its absorbance, and a standard working curve of absorbance-concentration was drawn.

[0143] The concentration of aldehyde substances in the extraction solution was calculated from the absorbance value of each sample extraction solution through the standard working curve. Three parallel samples were set for each sample group, and the average value was taken as the result.

[0144] The concentration of aldehyde substances detected at different time points in SBF solution for each sample is recorded in Table 2 below.

[0145] Table 2: Aldehyde concentration (μg / mL) in the leachate of each sample:

[0146] The data in Table 2 recorded the aldehyde concentration released by each sample in the simulated body fluid. The aldehyde concentration in the leachate of the sample of Example 1 increased continuously over time after soaking, reaching 22.8 μg / mL at 24 hours. The generation of aldehyde was also detected for the sample of Comparative Example 2, but its concentration was significantly lower than that of Example 1 at all time points, only 4.1 μg / mL at 24 hours. The aldehyde concentration in the leachate of the samples of Comparative Examples 3 and 4 remained at the detection baseline level throughout the test period.

[0147] The above results were due to the oxidative cleavage reaction between the internal potassium periodate (inert precursor A) and 1,2-cyclohexanediol-adipic acid copolymer oligomer (inert precursor B) of the non-woven fabric of Example 1 after contacting with the aqueous medium, thereby generating adipaldehyde in situ. The comparison of the data of Example 1 and Comparative Example 2 directly showed the function of the arginine bicarbonate component: the weak alkaline microenvironment established by this component in Example 1 made the generation rate of aldehyde much higher than that of Comparative Example 2 triggered by water only, confirming its acceleration effect on the in-situ chemical reaction.

[0148] The negative results of Comparative Examples 3 (lacking precursor B) and 4 (lacking precursor A) confirmed that the generation of aldehyde must rely on the simultaneous presence of the two precursors, which are the material basis for the in-situ chemical synthesis reaction. In summary, this test confirmed the feasibility of the technical solution of the present application: through the compounding of specific components, active substances can be synthesized in situ according to a predetermined chemical path when the material contacts with water, and the pH regulating component can effectively improve the efficiency of the synthesis process.

[0149] Test Example 3:

[0150] This test example aimed to quantitatively evaluate the in-vitro antibacterial activity of the degradable non-woven fabric prepared by the inventive example and each comparative example against Staphylococcus aureus and Escherichia coli.

[0151] The experimental procedure was as follows:

[0152] 1. Strain and bacterial suspension preparation: Staphylococcus aureus (ATCC 6538) and Escherichia coli (ATCC 8739) were inoculated in nutrient broth medium respectively and incubated at 37°C with 150 rpm for 18 hours. The bacterial solution in the logarithmic growth phase was diluted with phosphate buffered saline solution (PBS) to adjust its concentration to 1×10 5 -1×10 6 CFU / mL as the bacterial suspension to be tested.

[0153] 2. Sample preparation: The nonwoven fabrics prepared in Examples 1 to 4 and Comparative Examples 1 to 5 were cut into test samples of 0.4 g in weight under aseptic conditions.

[0154] 3. Co-culture test: Each of the test samples was placed in a sterile conical flask containing 20 mL of a bacterial suspension to be tested.

[0155] 4. Shaking culture: After all the conical flasks were sealed, they were placed in a constant-temperature shaking incubator at 37°C and 150 rpm for 24 hours of co-culture.

[0156] 5. Viable cell count: After the culture was completed, 1 mL of the bacterial solution was taken from each conical flask and diluted by 10 times in gradient with PBS. 100 μL of the bacterial solution of an appropriate dilution was uniformly spread on a nutrient agar plate. After the plate was inverted and incubated in a constant-temperature incubator at 37°C for 24 hours, the colonies on the plate were counted.

[0157] 6. Calculation of antibacterial rate: Comparative Example 1 (blank substrate) was used as a negative control group, and the antibacterial rate of each sample against the two strains was calculated according to the following formula. Three parallel samples were set for each sample group, and the results were averaged. Antibacterial rate (%) = [(control group viable cell count - experimental group viable cell count) / control group viable cell count] x 100%.

[0158] The antibacterial rate data of each sample against the two test strains are recorded in Table 3 below.

[0159] Table 3: Antibacterial rates of each sample against Staphylococcus aureus and Escherichia coli

[0160] The test data in Table 3 records the antibacterial rates of each sample against Staphylococcus aureus and Escherichia coli. The nonwoven fabrics prepared in Examples 1, 2, 3, and 4 all exhibit an antibacterial rate of more than 99.7% against the two test strains, and the antibacterial rates of Examples 1, 3, and 4 are more than 99.9%. As controls, the antibacterial rates of Comparative Example 1 (blank substrate), Comparative Example 3 (lacking oligomers), and Comparative Example 4 (lacking potassium periodate) are all less than 5.0%. The antibacterial rate of Comparative Example 2 (lacking arginine bicarbonate) is between 61.2% and 65.7%. The antibacterial rates of Comparative Example 5 (containing PHMB) against the two strains are 99.53% and 99.21%, respectively.

[0161] The above results prove the antibacterial effectiveness of the technical solution of the present application. The high antibacterial rates of Examples 1-4 are derived from the in-situ generated aldehyde compound in the aqueous environment, which inhibits the physiological activity of the bacteria by reacting with the bacterial proteins. The test results of Comparative Examples 3 and 4 are close to the blank control, which clearly indicates that the realization of the antibacterial function must rely on the coexistence of the two precursor components, i.e., potassium periodate and 1,2-cyclohexanediol-adipic acid copolymer oligomers, which are the material basis for the in-situ chemical reaction of the antibacterial substance.

[0162] The difference in antibacterial rate data between Example 1 and Comparative Example 2 reveals the function of pH regulation and catalyst component. In Comparative Example 2, which lacks this component, the antibacterial rate of the material is significantly lower than that of Example 1, which contains this component. This result corresponds to the data on the generation rate of aldehyde substances in Test Example 2, proving that the weak alkaline environment established by arginine bicarbonate accelerates the in-situ chemical reaction, thereby improving the generation efficiency of the antibacterial substance, and ultimately enabling the material to exhibit higher antibacterial activity. In addition, the data show that even Example 2, which uses a lower component content (antibacterial rate of 99.75%-99.81%), has a higher antibacterial rate value than Comparative Example 5, which uses a conventional antibacterial agent (antibacterial rate of 99.21%-99.53%), proving the effectiveness of this technical solution.

[0163] Test Example 4:

[0164] This test example aims to evaluate the in-vitro cytotoxicity of the leaching solution of the degradable non-woven fabric prepared in the examples and comparative examples of the present application to L929 fibroblasts according to the ISO 10993-5:2009 standard using the MTT method.

[0165] The experimental steps are as follows:

[0166] 1. Preparation of leaching solution:

[0167] Take the non-woven fabrics prepared in Examples 1-4 and Comparative Examples 1-5, respectively, and add them to sterile containers containing high-glucose DMEM complete medium (containing 10% fetal bovine serum and 1% penicillin-streptomycin) at a ratio of 0.2 g / mL (material weight / culture medium volume) under sterile conditions.

[0168] Place the containers in a cell culture incubator at 37°C with 5% CO2 and leach for 24 hours.

[0169] After the leaching is complete, filter the leaching solution through a 0.22 μm filter to remove bacteria and obtain the leaching solution of each sample. At the same time, use complete medium without samples as a negative control solution and complete medium containing 0.1% phenol as a positive control solution.

[0170] 2. Cell Culture and Seeding: L929 mouse fibroblasts in logarithmic growth phase were digested and counted. After adjusting the cell density, they were seeded into 96-well cell culture plates at a density of 5 × 10⁶ cells per well. 3 One cell was placed in a cell culture incubator at 37°C and 5% CO2 for 24 hours until the cells were fully adhered to the incubator.

[0171] 3. Cell treatment: Remove the original culture medium from the 96-well plate, and add 100 μL of the prepared sample extract, negative control solution, and positive control solution to each well. Set up 6 replicates for each group.

[0172] 4. MTT assay: Return the culture plate to the incubator and continue incubation for 24 hours. Then, add 20 μL of 5 mg / mL MTT solution to each well and continue incubation for 4 hours. After incubation, carefully aspirate the liquid from the wells and add 150 μL of dimethyl sulfoxide (DMSO) to each well. Shake slowly on a shaker for 10 minutes to completely dissolve the formazan crystals.

[0173] 5. Data Acquisition and Calculation: The absorbance (OD value) of each well was measured at a wavelength of 490 nm using a microplate reader. The relative cell proliferation rate (RGR) was calculated using the following formula: RGR(%) = (OD value of experimental group / OD value of negative control group) × 100%;

[0174] The relative cell proliferation rate (RGR) and cytotoxicity grade of each sample after treatment with extract are recorded in Table 4 below. Cytotoxicity grading criteria: RGR≥100%, Grade 0; 75%≤RGR<100%, Grade 1; 50%≤RGR<75%, Grade 2; 25%≤RGR<50%, Grade 3; RGR<25%, Grade 4.

[0175] Table 4. Relative cell proliferation rate (RGR) and cytotoxicity grade of extracts for each sample:

[0176] Table 4 shows that after treatment with the extracts of Examples 1, 2, 3, and 4, the relative cell growth rate (RGR) was above 88%, corresponding to a cytotoxicity grade of 1. The RGR values ​​of Comparative Examples 1, 2, 3, and 4 were also above 92%, with a toxicity grade of 1. In contrast, the RGR value of Comparative Example 5 was 68.4%, corresponding to a cytotoxicity grade of 2. The RGR value of the positive control group was 18.7%, exhibiting grade 4 toxicity.

[0177] The above results show that the nonwoven fabric compositions of Examples 1-4, including potassium periodate, oligomer and pH control agent, do not cause significant cytotoxicity in their leachates. The mechanism of action is that the active antimicrobial species is generated in situ by chemical reaction upon contact of the material with an aqueous environment, and its concentration is regulated by reaction kinetics. The reactants are present in solid form in the polymer matrix, avoiding the initial burst release of high concentrations of active species. This on-demand generation and controlled release mechanism allows the material as a whole to exhibit low cytotoxicity.

[0178] The RGR value of Comparative Example 5 is 68.4%, showing a cytotoxicity level of 2 (slight). In combination with the antibacterial rate data of Test Example 3, it can be seen that: Comparative Example 5, which directly adds conventional antibacterial agent PHMB, has a higher cytotoxicity level while achieving antibacterial activity comparable to the examples. While the technical solutions of Examples 1-4 maintain a cytotoxicity level of 1 while achieving an antibacterial rate of more than 99.7%. This comparison confirms that the technical solution of the present application, i.e. the approach of generating active species in situ from latent precursors in a specific environment, can effectively balance the antimicrobial functionality and biocompatibility of the material.

[0179] Although embodiments of the present application have been shown and described, it is to be understood that various modifications, substitutions, replacements and variations can be made to these embodiments without departing from the principles and spirit of the present application, and the scope of the present application is defined by the appended claims and their equivalents.

Claims

1. A degradable nonwoven fabric, characterized by, The non-woven fabric is made of components comprising the following weight parts: Polylactic acid: 58-68 parts; Polycaprolactone: 25-29 parts; Peroxydisulfate: 1-5 parts; Copolyester oligomer containing cis-1,2-cyclohexanediol structural units: 2-8 parts; Solid biocompatible weakly basic salt: 1-3 parts.

2. The degradable nonwoven fabric according to claim 1, characterized by The non-woven fabric is made of components comprising the following weight parts: Polylactic acid: 60-65 parts; Polycaprolactone: 25-30 parts; Peroxydisulfate: 2-4 parts; Copolyester oligomer containing cis-1,2-cyclohexanediol structural units: 4-6 parts; Solid biocompatible weakly basic salt: 1.5-2.5 parts.

3. The degradable nonwoven fabric according to claim 1, characterized by The copolyester oligomer containing cis-1,2-cyclohexanediol structural units is prepared by polycondensation reaction of cis-1,2-cyclohexanediol and adipic acid, and has a number average molecular weight of 1500-5000 g / mol.

4. The degradable nonwoven fabric according to claim 1, wherein The solid biocompatible weakly basic salt is arginine bicarbonate and / or trisodium citrate.

5. The degradable nonwoven fabric according to claim 1, wherein The peroxydisulfate is potassium peroxydisulfate.

6. A process for the production of a degradable nonwoven fabric as claimed in any one of claims 1 to 5, characterized in that, The method comprises the following steps: Mixing polylactic acid, polycaprolactone, peroxydisulfate, copolyester oligomer containing cis-1,2-cyclohexanediol structural units, and solid biocompatible weakly basic salt to obtain a mixture; Melt blending and melt blowing the mixture to obtain ultrafine fibers; Collecting the ultrafine fibers into a net to obtain a non-woven fabric.

7. The manufacturing process of claim 6, wherein, Before the mixing, the method further comprises a step of ball milling the peroxydisulfate.

8. The manufacturing process of claim 6, wherein, In the step of melt blending and melt blowing, the melt temperature is 195-215°C, and the hot air temperature is 200-230°C.

9. The manufacturing process of claim 8, wherein, The step of melt blending is performed in a twin-screw extruder, and the temperature of the metering zone and the die of the extruder is 190-210°C, and the screw rotation speed is 100-200 rpm.

10. The manufacturing process of claim 6, wherein, After the collecting into a net, the method further comprises a step of heat pressing the non-woven fabric, and the temperature of the heat pressing is 95-110°C.

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