Gradient-antibacterial absorbable suture and its preparation process

Abstract

This invention discloses a gradient antibacterial absorbable suture and its preparation process, belonging to the field of medical polymer materials. It addresses the technical problem that the mechanical properties and gradient antibacterial properties of absorbable sutures in the prior art need to be further improved. This invention constructs a core storage structure, an interlayer transition structure, and a surface functional configuration in the suture sequentially, so that triclosan forms a gradient distribution and continuous delivery path from the inside to the outside in the radial direction. This takes into account the initiation of surface antibacterial activity, continuous release in vivo, and maintenance of interface stability. While ensuring the strength of the absorbable suture, it achieves a coordinated unity of antibacterial function and structural performance.

Description

Technical Field

[0001] This invention relates to the field of medical polymer materials technology, specifically to gradient antibacterial absorbable sutures and their preparation process. Background Technology

[0002] Absorbable sutures are typically made from biodegradable polymers such as polyglycolic acid, polylactic acid, polydioxanone, and polyglycolic acid-lactide copolymer. They are used for wound closure, tissue suturing, and implantation fixation. To reduce the risk of suture-related infections, existing technologies also introduce antibacterial components such as triclosan onto the surface or inside of absorbable sutures. Common methods include surface coating, impregnation loading, co-extrusion, secondary finishing, and multi-layer coating, so that the suture has both antibacterial function and basic suturing performance after implantation.

[0003] However, conventional antibacterial absorbable sutures often exhibit either concentrated surface loading or uniform dispersion of antibacterial components. When concentrated surface loading occurs, antibacterial components tend to migrate rapidly from the outer surface in the early stages, resulting in a significant initial release, but their subsequent maintenance capacity is relatively limited. When uniformly dispersed, the internal components have a longer migration path to the outside, and the effective expression on the surface in the early stages is often insufficient. Therefore, it is often difficult to achieve both rapid surface onset and sustained maintenance in the middle and later stages within the same suture, and there is room for further optimization of the continuity of antibacterial function at different stages.

[0004] Furthermore, the introduction of antibacterial components also involves the synergistic stability of the suture matrix, surface treatment layer, and interlayer interfaces. If the loading position, coating structure, or treatment sequence of the antibacterial components is not properly controlled, insufficient stability of the surface functional area, uneven interlayer bonding, or fluctuations in the migration behavior of the antibacterial components may occur during use under conditions of liquid absorption, bending, friction, and knotting. This makes it difficult to form a stable coordination relationship between the antibacterial expression and mechanical maintenance of the suture, affecting the consistency of the material's function under actual use.

[0005] To address this technical deficiency, a solution is proposed. Summary of the Invention

[0006] The purpose of this invention is to provide a gradient antibacterial absorbable suture and its preparation process, in order to solve the technical problem that the mechanical properties and gradient antibacterial properties of absorbable sutures in the prior art need to be further improved.

[0007] The objective of this invention can be achieved through the following technical solution: a process for preparing gradient antibacterial absorbable sutures, comprising the following steps:

[0008] Step 1: Mix and react the antibacterial agent, ring-opening polymerizable monomer, and catalyst to obtain antibacterial low-polymer polyester;

[0009] Step 2: The absorbable polyester substrate, the antibacterial low-polymer polyester and the catalyst are mixed and then reacted and extruded into filaments to obtain gradient antibacterial composite core filaments.

[0010] Step 3: Place the gradient antibacterial composite core fiber in an alkaline reaction solution containing catecholamine compounds for surface deposition reaction to obtain controlled-release coated core fiber;

[0011] Step 4: The controlled-release coated core filament is placed in a reaction solution containing film-forming material and antibacterial components for impregnation reaction, and then post-treated to obtain a gradient antibacterial absorbable suture.

[0012] Further, in step one, the preparation method of the antibacterial low-polyester is as follows: triclosan and ε-caprolactone are added to a reaction vessel and stirred. After mixing evenly, glycolide is added and stirring is continued until evenly dispersed. Stannous octoate is then added. Subsequently, the reaction vessel is heated to 140-150℃ and stirred for 4-6 hours. Afterward, vacuum is applied for 20-40 minutes, and the temperature is lowered to 100-115℃ before discharging. The antibacterial low-polyester is then obtained through post-treatment.

[0013] Furthermore, in the preparation of antibacterial low-polyester, the ratio of triclosan, ε-caprolactone, glycolide, and stannous octoate is 5-7g:30-40mL:15-21g:0.04-0.07mL. Post-processing includes: pouring the output material into a mold for cooling, chopping it into 2-4mm particles, and then transferring the particles to a drying oven at 35-45℃ for vacuum drying for 4-6 hours to obtain the antibacterial low-polyester.

[0014] Furthermore, in step two, the preparation method of the gradient antibacterial composite core wire is as follows: add polydioxanone to a mixer and stir, then add antibacterial low polyester and continue mixing. After mixing evenly, add stannous octoate, then add the mixture to a reaction extruder, heat it in sections to 155-170℃ and keep it at that temperature for 8-12 minutes, and then perform post-treatment to obtain the gradient antibacterial composite core wire.

[0015] Furthermore, in the preparation of the gradient antibacterial composite core wire, the ratio of poly(p-dioxanone), antibacterial low-polyester, and stannous octoate is 88-96g:6-10g:0.01-0.03mL, wherein the cross-sectional radius of the gradient antibacterial composite core wire is 0.05-0.7mm. The post-processing includes: after heat preservation, extruding the wire into filaments through a spinneret, cooling the extruded filaments at 20-25℃, then stretching them 3.0-3.8 times at 45-55℃, and then winding them to obtain the gradient antibacterial composite core wire.

[0016] Furthermore, in step three, the controlled-release coated core fiber is prepared as follows: purified water and tris(hydroxymethyl)aminomethane are added to a reaction vessel and stirred. After mixing evenly, 5-8 wt% hydrochloric acid aqueous solution is added to adjust the pH value of the system to 8.4-8.6. Then, dopamine hydrochloride is added and stirring is continued until completely dissolved. Subsequently, gradient antibacterial composite core fiber is added, the reaction vessel is heated to 20-30℃, and stirred for 3-5 hours. The controlled-release coated core fiber is obtained after post-treatment.

[0017] Furthermore, in the process of preparing the controlled-release coated core fiber, the ratio of purified water, tris(hydroxymethyl)aminomethane, dopamine hydrochloride, and gradient antibacterial composite core fiber is 900-1100mL:1.0-1.4g:1.6-2.4g:10-14g. The post-treatment includes: after the reaction is completed, the fiber is taken out, rinsed with purified water 2-4 times, and then placed in a drying oven at 35-45℃ for vacuum drying for 1.5-3.0h to obtain the controlled-release coated core fiber.

[0018] Further, in step four, the preparation method of the gradient antibacterial absorbable suture is as follows: purified water and glacial acetic acid are added to a reaction vessel and stirred. After mixing evenly, chitosan is added and stirred continuously until dissolved. Then, 1-3 wt% sodium hydroxide aqueous solution is added to adjust the pH value of the system to 5.4-5.8. Subsequently, 20 wt% chlorhexidine gluconate aqueous solution is added and stirred continuously. After mixing evenly, controlled-release coated core wire is added. The reaction vessel is heated to 25-35℃ and kept warm for 15-25 minutes. The gradient antibacterial absorbable suture is then obtained through post-treatment.

[0019] Furthermore, in the preparation of chitosan-chlorhexidine surface antibacterial composite sutures, the ratio of purified water, glacial acetic acid, chitosan, 20wt% chlorhexidine gluconate aqueous solution, and controlled-release coated core filaments is 90-110mL:0.8-1.2mL:0.5-0.7g:0.5-0.8mL:10-14g. The post-treatment includes: curing the impregnated filaments at 40-50℃ for 30-60min, then quickly rinsing 1-2 times, followed by vacuum drying in a drying oven at 30-40℃ for 3-5h, stretching and shaping by 1.2-1.5 times, then winding, sterilizing, and sealing the sutures to obtain gradient antibacterial absorbable sutures.

[0020] The present invention also discloses a gradient antibacterial absorbable suture, which is prepared using the above-mentioned gradient antibacterial absorbable suture preparation process.

[0021] The present invention has the following beneficial effects:

[0022] 1. After the drug-rich surface layer formed by the first modification is placed on the outside of the absorbable suture matrix, when the suture enters the service environment, the drug components first establish an exchange interface with the external medium along the outer surface, so that the functional expression starts from the surface layer. The sustained-release transition layer located inside it does not repeat the surface layer configuration, but forms a continuous and progressive drug-loading area between the drug-rich surface layer and the absorbable suture matrix, so that after the surface release is initiated, the interior still maintains the basis for continued outward delivery. The outer fixation layer formed by the third modification maintains the interlayer adhesion state and the migration rhythm during operation, so that the drug presents a more coherent distribution relationship in the initial release, sustained release and subsequent decay process, thereby helping to improve the release regulation performance and sustained drug release performance of the suture.

[0023] 2. The sustained-release transition layer formed after the second modification is located between the drug-rich surface layer and the absorbable suture matrix. Its configuration allows the suture to not only form an active interface earlier when in contact with external microorganisms, but also maintain a continuous supply relationship below the interface. Specifically, the drug-rich surface layer first participates in the functional presentation of the outer surface, so that a drug-accessible area is formed at the initial contact stage; the sustained-release transition layer then maintains the connection between the expression on the outer surface and the internal drug migration, thereby avoiding the initial effect being only a short-term exposure; the outer fixation layer formed after the third modification further maintains the surface configuration and interlayer adhesion relationship, so that the suture maintains a relatively stable functional interface state during liquid absorption, bending and knotting operations, thereby helping to improve the antibacterial properties, antibacterial persistence and antibacterial stability of the suture during use.

[0024] 3. The absorbable suture matrix constitutes the main load-bearing structure of the suture. The drug-rich surface layer formed by the first modification, the sustained-release transition layer formed by the second modification, and the outer fixation layer formed by the third modification are all attached to and configured on this main structure. The drug-rich surface layer is responsible for the expression of the outer surface function, but its configuration does not cause obvious discontinuity in the outer layer of the suture. The sustained-release transition layer is located between the functional configuration and the main matrix, further coordinating the interlayer transition relationship, so that each layer maintains a relatively consistent compatibility when there is local bending, compression, and nodule formation. The outer fixation layer keeps the aforementioned functional units stably attached during use, thereby keeping the functional configuration and the continuity of the suture structure in the same system, which helps to improve the mechanical stability, structural integrity, and clinical reliability of the suture. Attached Figure Description

[0025] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0026] Figure 1 SEM images of the gradient antibacterial absorbable sutures prepared in Example 3 of the present invention are shown. Detailed Implementation

[0027] The technical solution of the present invention will be clearly and completely described below with reference to the embodiments. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0028] In this application, the polydioxanone used was purchased from Shanghai Maclean Biochemical Technology Co., Ltd., with the product number P693431.

[0029] Example 1

[0030] This embodiment provides a method for preparing a gradient antibacterial absorbable suture, including the following steps:

[0031] Step 1: Preparation of antibacterial low-polyester

[0032] Weigh out 5.0g of triclosan and 30.0mL of ε-caprolactone and add them to the reaction vessel. Stir until the mixture is uniform, then add 15.0g of glycolide and continue stirring until it is evenly dispersed. Add 0.04mL of stannous octoate, then heat the reaction vessel to 140℃ and stir for 4 hours. After that, evacuate the vacuum for 20 minutes, cool down to 100℃ and discharge the material. Pour the discharged material into a mold to cool, cut it into 2mm particles, and then transfer the particles to a drying oven at 35℃ and vacuum dry for 4 hours to obtain antibacterial low-polyester.

[0033] The reaction principle for preparing antibacterial low-polyester is as follows:

[0034] Under stannous octoate catalysis, ε-caprolactone undergoes coordination activation and ring-opening with the cyclic ester structure of glycolide, gradually generating oligomeric segments containing repeating ester bonds. The phenolic hydroxyl groups in the triclosan molecule can participate in initiation or chain transfer-related processes and chemically link with the ring-opened monomer segments, thus entering the oligopolyester system. As the reaction proceeds, caprolactone and glycolide units continuously insert to achieve chain growth, forming a oligopolyester component composed of both types of units. The chemical nature of this process can be attributed to a cyclic ester ring-opening copolymerization reaction catalyzed by stannous octoate.

[0035] Step 2: Preparation of gradient antibacterial composite core wire

[0036] Weigh out 88.0g of polydioxanone and add it to the mixer and stir. Then add 6.0g of antibacterial low polyester and continue mixing. After mixing evenly, add 0.01mL of stannous octoate and then add the mixture to the reaction extruder. Heat the mixture in sections to 155℃ and hold for 8 minutes. After the holding time is completed, extrude the mixture into filaments through the spinneret. Cool the extruded filaments at 20℃ and then stretch them 3.0 times at 45℃. Then wind them to obtain a gradient antibacterial composite core filament with a cross-sectional radius of 0.3mm.

[0037] The reaction principle for preparing gradient antibacterial composite core wire is as follows:

[0038] Under thermal conditions and in the presence of stannous octoate, poly(p-dioxanone) and antibacterial low-polyester form a melt composite system. The molecular chains of the two molecules come into contact and become entangled in the melt state, which may be accompanied by a certain degree of transesterification or chain segment rearrangement, thereby enhancing the bonding between different components. During the extrusion process, the material is affected by the temperature field, shear field, and flow field. The antibacterial low-polyester can form a relatively non-uniform spatial distribution inside the filament. After subsequent cooling and stretching, this distribution state is maintained, and the resulting filament exhibits a composite structure with radial compositional differences. Essentially, this is a reaction composite and filament shaping process of polyester materials under melt processing conditions.

[0039] Step 3: Preparation of controlled-release coated core fibers

[0040] Weigh out 900.0 mL of purified water and 1.0 g of tris(hydroxymethyl)aminomethane and add them to the reaction vessel. Stir and mix well. Then add 5 wt% hydrochloric acid aqueous solution to adjust the pH of the system to 8.4. Add 1.6 g of dopamine hydrochloride and continue stirring until completely dissolved. Then add 10.0 g of gradient antibacterial composite core fiber. Heat the reaction vessel to 20°C and keep it at that temperature for 3 hours. After the reaction is complete, take out the fiber material, rinse it twice with purified water, and then place it in a drying oven at 35°C for vacuum drying for 1.5 hours to obtain controlled-release coated core fiber.

[0041] The reaction principle for preparing controlled-release coated core fibers is as follows:

[0042] In a weakly alkaline aqueous system buffered by tris(hydroxymethyl)aminomethane, after the dissociation of dopamine hydrochloride, its catechol structure can be oxidized to generate the corresponding quinone intermediate. Subsequently, it undergoes transformations such as intramolecular cyclization, intermolecular condensation, and coupling to gradually form polydopamine components. The above process is accompanied by interfacial interactions between functional groups such as catechol groups and quinone groups and the surface of the filament, causing the generated polydopamine to be deposited on the surface of the gradient antibacterial composite core filament and form a coating layer. The chemical nature of this process can be described as the oxidative self-polymerization of dopamine under weakly alkaline conditions and its surface deposition process.

[0043] Step 4: Prepare graded antibacterial absorbable sutures

[0044] Weigh out 90.0 mL of purified water and 0.8 mL of glacial acetic acid and add them to the reaction vessel. Stir until well mixed, then add 0.5 g of chitosan and continue stirring until dissolved. Add 1 wt% sodium hydroxide aqueous solution to adjust the pH of the system to 5.4. Then add 0.5 mL of 20 wt% chlorhexidine gluconate aqueous solution and continue stirring until well mixed. Add 10.0 g of controlled-release coated core filament. Heat the reaction vessel to 25°C and keep it warm for 15 min. Cure the impregnated filament at 40°C for 30 min, then rinse it once quickly. Then place it in a drying oven at 30°C and vacuum dry for 3 h. Perform 1.2 times stretching and shaping, then wind, sterilize and seal the package to obtain gradient antibacterial absorbable suture.

[0045] The reaction principle for preparing gradient antibacterial absorbable sutures is as follows:

[0046] In glacial acetic acid aqueous solution, the amino groups in chitosan molecules are protonated and dispersed in the system. After adjusting to weakly acidic conditions with sodium hydroxide, the interaction state between chitosan molecular chains changes, and the system becomes ready for further deposition and film formation. After adding chlorhexidine gluconate, its molecules can form hydrogen bonds and other intermolecular interactions with chitosan segments, and undergo interfacial adsorption and intermolecular interactions with the polydopamine layer on the surface of the controlled-release coated core filament. This causes the chitosan and chlorhexidine gluconate-related components to adhere to the outer layer of the filament. After curing and drying, the surface components further approach and rearrange, forming a relatively stable surface composite coating structure.

[0047] Example 2

[0048] This embodiment provides a method for preparing a gradient antibacterial absorbable suture, including the following steps:

[0049] Step 1: Preparation of antibacterial low-polyester

[0050] Weigh out 7.0g of triclosan and 40.0mL of ε-caprolactone and add them to the reaction vessel. Stir until the mixture is uniform, then add 21.0g of glycolide and continue stirring until it is evenly dispersed. Add 0.07mL of stannous octoate, then heat the reaction vessel to 150℃ and stir for 6 hours. After that, evacuate the vacuum for 40 minutes, cool down to 115℃ and discharge the material. Pour the discharge into a mold to cool, cut it into 4mm particles, and then transfer the particles to a drying oven at 45℃ and vacuum dry for 6 hours to obtain antibacterial low-polyester.

[0051] Step 2: Preparation of gradient antibacterial composite core wire

[0052] Weigh out 96.0g of polydioxanone and add it to the mixer and stir. Then add 10.0g of antibacterial low polyester and continue mixing. After mixing evenly, add 0.03mL of stannous octoate and then add the mixture to the reactive extruder. Heat the mixture in sections to 170℃ and hold for 12min. After holding, extrude the mixture into filaments through the spinneret. Cool the extruded filaments at 25℃ and then stretch them 3.8 times at 55℃. Then wind them to obtain a gradient antibacterial composite core filament with a cross-sectional radius of 0.3mm.

[0053] Step 3: Preparation of controlled-release coated core fibers

[0054] Weigh out 1100.0 mL of purified water and 1.4 g of tris(hydroxymethyl)aminomethane and add them to the reaction vessel. Stir and mix well. Then add 8 wt% hydrochloric acid aqueous solution to adjust the pH of the system to 8.6. Add 2.4 g of dopamine hydrochloride and continue stirring until completely dissolved. Then add 14.0 g of gradient antibacterial composite core fiber. Heat the reaction vessel to 30°C and keep it at that temperature for 5 h. After the reaction is complete, take out the fiber material, rinse it 4 times with purified water, and then place it in a drying oven at 45°C for vacuum drying for 3.0 h to obtain controlled-release coated core fiber.

[0055] Step 4: Prepare graded antibacterial absorbable sutures

[0056] Weigh out 110.0 mL of purified water and 1.2 mL of glacial acetic acid and add them to the reaction vessel. Stir until the mixture is homogeneous, then add 0.7 g of chitosan and continue stirring until dissolved. Add 3 wt% sodium hydroxide aqueous solution to adjust the pH of the system to 5.8. Then add 0.8 mL of 20 wt% chlorhexidine gluconate aqueous solution and continue stirring until homogeneous. Add 14.0 g of controlled-release coated core filament. Heat the reaction vessel to 35°C and keep it warm for 25 min. Cure the impregnated filament at 50°C for 60 min, then rinse it twice quickly. Then place it in a drying oven at 40°C and vacuum dry for 5 h. Perform 1.5 times stretching and shaping, then wind it, sterilize and seal it to obtain gradient antibacterial absorbable suture.

[0057] Example 3

[0058] This embodiment provides a method for preparing a gradient antibacterial absorbable suture, including the following steps:

[0059] Step 1: Preparation of antibacterial low-polyester

[0060] Weigh out 6.0g of triclosan and 35.0mL of ε-caprolactone and add them to the reactor. Stir until the mixture is homogeneous, then add 18.0g of glycolide and continue stirring until evenly dispersed. Add 0.06mL of stannous octoate, then heat the reactor to 145℃ and stir for 5 hours. After that, evacuate the reactor for 30 minutes, cool it down to 108℃, and then discharge the material. Pour the discharged material into a mold to cool, cut it into 3mm particles, and then transfer the particles to a drying oven at 40℃ and vacuum dry for 5 hours to obtain antibacterial low-polyester.

[0061] Step 2: Preparation of gradient antibacterial composite core wire

[0062] Weigh out 92.0g of polydioxanone and add it to the mixer and stir. Then add 8.0g of antibacterial low polyester and continue mixing. After mixing evenly, add 0.02mL of stannous octoate and then add the mixture to the reactive extruder. Heat the mixture in sections to 163℃ and hold for 10min. After holding, extrude the mixture into filaments through the spinneret. Cool the extruded filaments at 23℃ and then stretch them 3.4 times at 50℃. Then wind them to obtain a gradient antibacterial composite core filament with a cross-sectional radius of 0.3mm.

[0063] Step 3: Preparation of controlled-release coated core fibers

[0064] Weigh 1000.0 mL of purified water and 1.2 g of tris(hydroxymethyl)aminomethane and add them to the reaction vessel. Stir and mix well. Then add 7 wt% hydrochloric acid aqueous solution to adjust the pH of the system to 8.5. Add 2.0 g of dopamine hydrochloride and continue stirring until completely dissolved. Then add 12.0 g of gradient antibacterial composite core fiber. Heat the reaction vessel to 25°C and keep it at that temperature for 4 hours. After the reaction is complete, take out the fiber material, rinse it three times with purified water, and then place it in a drying oven at 40°C for vacuum drying for 2.3 hours to obtain controlled-release coated core fiber.

[0065] Step 4: Prepare graded antibacterial absorbable sutures

[0066] Weigh out 100.0 mL of purified water and 1.0 mL of glacial acetic acid and add them to the reaction vessel. Stir until well mixed, then add 0.6 g of chitosan and continue stirring until dissolved. Add 2 wt% sodium hydroxide aqueous solution to adjust the pH of the system to 5.6. Then add 0.7 mL of 20 wt% chlorhexidine gluconate aqueous solution and continue stirring until well mixed. Add 12.0 g of controlled-release coated core filament. Heat the reaction vessel to 30°C and keep it warm for 20 min. Cure the impregnated filament at 45°C for 45 min, then rinse it twice quickly. Then place it in a drying oven at 35°C and vacuum dry for 4 h. Perform 1.4 times stretching and shaping, then wind, sterilize and seal the package to obtain gradient antibacterial absorbable suture.

[0067] Comparative Example 1

[0068] The difference between this comparative example and Example 3 is that triclosan was omitted in step one.

[0069] Comparative Example 2

[0070] The difference between this comparative example and Example 3 is that step three is omitted.

[0071] Comparative Example 3

[0072] The difference between this comparative example and Example 3 is that step four is omitted.

[0073] Performance testing:

[0074] The gradient antibacterial absorbable sutures prepared in Examples 1-3 and Comparative Examples 1-3 were used as test samples. Unless otherwise specified, the same specification sutures were used in each group of samples. Parallel samples were set up for each test. The gradient release / controlled release performance, antibacterial time performance and mechanical practical performance were measured. The breaking strength after knotting was measured according to YY1116-2020 "Absorbable Surgical Sutures"; the sample preparation for the release test was carried out in accordance with GB / T 16886.12-2023 "Biological Evaluation of Medical Devices Part 12: Sample Preparation and Reference Materials"; the 10-minute rapid antibacterial rate was measured according to the principle of oscillation contact and viable bacteria counting in GB / T 20944.3-2008 "Evaluation of Antibacterial Properties of Textiles Part 3: Oscillation Method".

[0075] The graded antibacterial absorbable sutures prepared in Examples 1-3 and Comparative Examples 1-3 were used to measure the amount of triclosan released from their surfaces over 4 hours. The results were expressed in μg / cm³. 2 The procedure involved taking six sutures, each 10.0 cm in length, from each group, and calculating the result based on the suture's outer surface area. Each sample was placed in a stoppered glass bottle, and 10.0 mL of release medium (pH 7.4 phosphate buffer / ethanol = 80 / 20, V / V) was added. The samples were then placed in a constant-temperature shaker at 37.0 ± 0.5 °C and shaken at 60 rpm for 4 hours. After the shake, the released liquid was collected, filtered through a 0.22 μm filter, and analyzed by high-performance liquid chromatography (HPLC). The chromatographic conditions were: C18 column (250 mm × 4.6 mm, 5 μm), mobile phase acetonitrile / water = 75 / 25 (V / V), detection wavelength 280 nm, flow rate 1.0 mL / min, column temperature 30 °C, injection volume 10 μL. A standard curve was established using triclosan as a reference standard. The triclosan content in the released liquid was calculated and converted to μg / cm² based on the sample surface area. 2 ;

[0076] The graded antibacterial absorbable sutures prepared in Examples 1-3 and Comparative Examples 1-3 were used to determine their 14-day maintenance release levels. The results were expressed in μg / cm³. 2The procedure involved taking six additional sutures, each 10.0 cm long, from each group and placing them in 10.0 mL of the same release medium. Extraction was performed continuously at 37.0 ± 0.5 °C and 60 r / min. The release medium was completely replaced every 24 hours starting from day 1. After replacing with fresh medium on day 13, extraction continued until day 14. The release solution from day 13 to day 14 was collected, and the triclosan content was determined using the aforementioned high-performance liquid chromatography conditions. The resulting solution was then converted to the 14-day maintenance release amount based on the sample surface area.

[0077] The graded antibacterial absorbable sutures prepared in Examples 1-3 and Comparative Examples 1-3 were used to determine the residual amount of triclosan after 21 days. The results were expressed in μg / cm³. 2 The procedure involved removing the sutures after the 21-day release test, gently rinsing the surface with purified water, aspirating the liquid, and vacuum drying at 25°C to constant weight. Three dried samples from each group were cut into small pieces and placed in stoppered centrifuge tubes. 10.0 mL of a methanol / tetrahydrofuran (90 / 10, V / V) extraction buffer was added, and the samples were ultrasonically extracted at 40°C for 30 min. After standing, the supernatant was collected. This extraction was repeated once more. The extracts were combined and brought to a final volume of 25.0 mL. After filtration through a 0.22 μm filter, the triclosan content was determined using the aforementioned high-performance liquid chromatography (HPLC) conditions and converted to μg / cm² based on the sample surface area. 2 .

[0078] The gradient antibacterial absorbable sutures prepared in Examples 1-3 and Comparative Examples 1-3 were used to determine their rapid antibacterial rate over 10 minutes. The results are expressed as a percentage (%). This project followed the oscillation method principle of GB / T 20944.3-2008. Without changing the basic principles of oscillation contact and viable cell counting, the bacterial suspension contact time was fixed at 10 minutes. Staphylococcus aureus ATCC 6538 was selected as the test bacterium, and the initial concentration of the bacterial suspension was controlled at 3.0 × 10⁻⁶. 5 CFU / mL, take 0.20g±0.01g of suture sample for each group, cut it into short segments of about 1cm in length and place them in a 50mL Erlenmeyer flask, add 20.0mL of bacterial suspension, and shake at 150r / min for 10min in a constant temperature shaker at 37℃. Immediately after contact, add 20.0mL of neutralizing solution to terminate the antibacterial effect, shake thoroughly to mix, and then dilute stepwise and determine the number of surviving bacteria using the plate count method.

[0079] Calculate the rapid antibacterial rate using the following formula:

[0080] Rapid antibacterial rate (%) = (B−A) / B×100%, where A is the number of colonies recovered after 10 min in the sample group and B is the number of colonies recovered after 10 min in the blank control group. This item is used to characterize the immediate antibacterial ability of the outermost layer of the suture.

[0081] The graded antibacterial absorbable sutures prepared in Examples 1-3 and Comparative Examples 1-3 were used to determine their tensile strength after knotting. The results are expressed as N. This test was conducted in accordance with YY 1116-2020 "Absorbable Surgical Sutures". Ten sutures were taken from each group. After being taken out of the packaging, a simple knot was tied in the middle and tightened so that the knot was located in the middle of the sample. Tensile tests were performed using an electronic universal testing machine. The gauge length between the clamps was set to 130 mm ± 5 mm, and the tensile speed was set to 300 mm / min ± 10 mm / min. During the test, both ends of the suture were clamped in the upper and lower clamps respectively, so that the knot was located in the middle of the two clamps. The suture was stretched uniformly along the axial direction until it broke. The maximum force value was recorded as the tensile strength after knotting of the sample. If the break point was within 1 cm from the edge of the clamp, the result was invalidated and a retest was conducted. The final test result was expressed as the average value of 10 parallel samples. The specific data are shown in Table 1.

[0082] Table 1 - Performance Test Data for Each Sample

[0083]

[0084] Data Analysis:

[0085] A comparative analysis of the data in Table 1 reveals that the 4-hour surface triclosan release of the gradient antibacterial absorbable suture prepared in this invention is 5.9 μg·cm³. -2 The sustained release rate after 14 days was 6.1 μg·cm³. -2 The residual amount of triclosan after 21 days was 0.35 μg·cm³. -2 The rapid antibacterial rate within 10 minutes was 96.2%, and the tensile strength after knotting was 15.4N. All data were superior to the comparative example, indicating that:

[0086] In the sample obtained in Comparative Example 1, an endogenous functional storage region that integrates with the main matrix was not established inside the line body. As a result, the system lacked a progressive distribution foundation from the inside to the outside in the radial direction. Consequently, after the outer layer function initially participated, it was difficult for the sample to achieve continuous replenishment through the internal structure, which weakened the coupling relationship between the surface expression and the internal support. Furthermore, the continuous transmission path that should have been composed of the core, transition region and outer layer was weakened, the stage continuity of the system in the time dimension decreased, and the gradient consistency in the spatial dimension was also destroyed. As a result, the sample could not simultaneously take into account the initial effect, continuous maintenance and subsequent retention, and ultimately showed a systematic decline in the overall composite effect.

[0087] In the sample obtained in Comparative Example 2, there is a lack of a stable intermediate transition interface between the composite core filament and the outer functional structure. This results in the failure to form an effective interlayer connection mechanism between the internal drug-loading region and the external surface action region. In this case, although the system still has a certain functional basis between the inner and outer layers, the transmission relationship between the two tends to be separated, making it difficult to form a continuous and controllable migration channel. Consequently, there is a significant disconnect between the front-end surface expression and the subsequent internal continuation. At the same time, due to the lack of coordination between the intermediate interface and the interlayer adhesion state and structural synergy, the filament is more prone to local interface fluctuations under wet, bent, and nodular conditions, which further reduces the uniformity and stability of the overall functional output. Therefore, the composite performance shows a significant decline.

[0088] In the sample obtained in Comparative Example 3, no effective surface functional configuration was formed on the outer side of the line, resulting in a lack of an interface basis between the outermost layer of the system and the usage environment that could directly participate in the interaction. As a result, although the sample still retains the internal storage structure and interlayer progression relationship, the internal function needs to go through a longer diffusion and migration path when it is transferred outward, which limits the efficiency of the establishment of the external surface response and makes it difficult to form a stable interface interaction state in a timely manner. Furthermore, after the outer layer configuration is missing, the original hierarchical synergistic mode of "surface initiation-internal continuation-overall maintenance" is destroyed, making it difficult to achieve synchronous matching between the external surface expression and the internal gradient configuration, thereby weakening the overall performance of the system in terms of structural integrity, functional coherence and operational stability, and ultimately causing a decrease in the overall composite effect of the sample.

[0089] In conclusion, the material behavior of the sample in this application is not determined by the local contribution of a single functional layer, but is jointly shaped by a continuous system consisting of core storage, interlayer transition, and surface configuration arranged in the process sequence. This system enables the functional components to form a progressive distribution in the radial direction, and during operation, it forms a transmission relationship of surface initiation, inner layer continuation, and interface maintenance, and maintains a certain consistency of the above relationship under conditions of liquid absorption, bending, and nodulation. After weakening different links in the continuous system in the comparative model, the sample showed corresponding changes in stage connection, interface stability, and overall coordination. It can be seen that the scheme of this application is closer to a systematic material configuration formed by multi-step organization.

[0090] The preferred embodiments of the present invention disclosed above are merely illustrative of the invention. These preferred embodiments do not exhaustively describe all details, nor do they limit the invention to specific implementations. Clearly, many modifications and variations can be made based on the content of this specification. This specification selects and specifically describes these embodiments to better explain the principles and practical applications of the invention, thereby enabling those skilled in the art to better understand and utilize the invention. The invention is limited only by the claims and their full scope and equivalents.

Claims

1. A process for preparing graded antibacterial absorbable sutures, characterized in that, Includes the following steps: Step 1: Mix and react the antibacterial agent, ring-opening polymerizable monomer, and catalyst to obtain antibacterial low-polymer polyester; Step 2: The absorbable polyester substrate, the antibacterial low-polymer polyester and the catalyst are mixed and then reacted and extruded into filaments to obtain gradient antibacterial composite core filaments; Step 3: Place the gradient antibacterial composite core fiber in an alkaline reaction solution containing catecholamine compounds for surface deposition reaction to obtain controlled-release coated core fiber; Step 4: The controlled-release coated core filament is placed in a reaction solution containing film-forming material and antibacterial components for impregnation reaction, and then post-treated to obtain a gradient antibacterial absorbable suture.

2. The preparation process of the gradient antibacterial absorbable suture according to claim 1, characterized in that, In step one, the preparation method of the antibacterial low-polyester is as follows: triclosan and ε-caprolactone are added to a reaction vessel and stirred. After mixing evenly, glycolide is added and stirring is continued until evenly dispersed. Stannous octoate is then added. Subsequently, the reaction vessel is heated to 140-150℃ and stirred for 4-6 hours. Afterward, vacuum is applied for 20-40 minutes, and the temperature is lowered to 100-115℃ before discharging. The antibacterial low-polyester is obtained after post-treatment.

3. The preparation process of the gradient antibacterial absorbable suture according to claim 2, characterized in that, In the preparation of antibacterial low-polyester, the ratio of triclosan, ε-caprolactone, glycolide, and stannous octoate is 5-7g:30-40mL:15-21g:0.04-0.07mL.

4. The preparation process of the gradient antibacterial absorbable suture according to claim 1, characterized in that, In step two, the preparation method of the gradient antibacterial composite core wire is as follows: add polydioxanone to a mixer and stir, then add antibacterial low polyester and continue mixing. After mixing evenly, add stannous octoate, then add the mixture to a reaction extruder, heat it in sections to 155-170℃ and keep it at that temperature for 8-12 minutes, and then perform post-treatment to obtain the gradient antibacterial composite core wire.

5. The preparation process of the gradient antibacterial absorbable suture according to claim 4, characterized in that, In the process of preparing gradient antibacterial composite core wire, the ratio of poly(p-dioxanone), antibacterial low-polyester, and stannous octoate is 88-96g:6-10g:0.01-0.03mL, wherein the cross-sectional radius of the gradient antibacterial composite core wire is 0.05-0.7mm.

6. The preparation process of the gradient antibacterial absorbable suture according to claim 1, characterized in that, In step three, the controlled-release coated core fiber is prepared as follows: purified water and tris(hydroxymethyl)aminomethane are added to a reaction vessel and stirred. After mixing evenly, 5-8 wt% hydrochloric acid aqueous solution is added to adjust the pH value of the system to 8.4-8.

6. Then, dopamine hydrochloride is added and stirring is continued until completely dissolved. Gradient antibacterial composite core fiber is then added. The reaction vessel is heated to 20-30℃ and kept at this temperature for 3-5 hours. The controlled-release coated core fiber is then obtained through post-treatment.

7. The preparation process of the gradient antibacterial absorbable suture according to claim 6, characterized in that, In the process of preparing the controlled-release coated core fiber, the ratio of purified water, tris(hydroxymethyl)aminomethane, dopamine hydrochloride, and gradient antibacterial composite core fiber is 900-1100mL:1.0-1.4g:1.6-2.4g:10-14g.

8. The preparation process of the gradient antibacterial absorbable suture according to claim 1, characterized in that, In step four, the preparation method of the gradient antibacterial absorbable suture is as follows: purified water and glacial acetic acid are added to a reaction vessel and stirred. After mixing evenly, chitosan is added and stirred continuously until dissolved. Then, 1-3 wt% sodium hydroxide aqueous solution is added to adjust the pH value of the system to 5.4-5.

8. Subsequently, 20 wt% chlorhexidine gluconate aqueous solution is added and stirred continuously. After mixing evenly, controlled-release coated core wire is added. The reaction vessel is heated to 25-35℃ and kept warm for 15-25 minutes. The gradient antibacterial absorbable suture is obtained after post-treatment. The ratio of purified water, glacial acetic acid, chitosan, 20 wt% chlorhexidine gluconate aqueous solution, and controlled-release coated core wire is 90-110 mL: 0.8-1.2 mL: 0.5-0.7 g: 0.5-0.8 mL: 10-14 g.

9. A graded antibacterial absorbable suture, characterized in that, The gradient antibacterial absorbable suture is prepared using the preparation process of the gradient antibacterial absorbable suture as described in any one of claims 1-8.

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