Suture with instant long-lasting analgesic function and preparation method thereof

Abstract

This invention belongs to the field of biomaterials and relates to a suture with immediate, sustained, and long-lasting analgesic function and its preparation method. The preparation method includes the following steps: using elastic fibers in a stretched state as the receiving substrate, electrospinning is performed on the fibers with an electrospinning solution containing analgesic drugs; the stretching force on the elastic fibers is then removed to obtain a yarn with a surface wrinkled topology; the yarn with the surface wrinkled topology is sequentially heat-set and cool-set to fix the surface wrinkled topology; the elastic fibers in the yarn with the surface wrinkled topology are extracted to obtain a hollow nanofiber; and the yarn is impregnated to obtain the suture with immediate, sustained, and long-lasting analgesic function. The prepared suture with immediate, sustained, and long-lasting analgesic function avoids the initial burst release of the drug, maintains the mechanical integrity of the suture, prevents knot slippage, displacement, and drug inactivation, and achieves the immediate, sustained, and long-lasting analgesic function of the suture.

Description

Technical Field

[0001] This invention belongs to the field of biomaterials and relates to a suture with immediate, continuous and long-lasting analgesic function and its preparation method. Background Technology

[0002] Surgical sutures, as one of the most widely used medical devices in clinical surgery, play a crucial role in the closure and healing of damaged tissues and organs after surgery. They can be used for various surgical incisions, severed blood vessels, and any form of traumatic tissue, such as tendons, nerves, and muscles. Sutures have undergone changes in both materials and structure, significantly improving their mechanical support properties and biosafety during tissue closure. However, they cannot alleviate pain generated during wound healing. Especially during postoperative wound healing, nerve traction and inflammatory responses cause wound pain, and pain lasting 72 hours or more can delay wound healing, increase the risk of complications, and severely impact patients' quality of life. However, existing sutures themselves do not possess analgesic properties, forcing patients to rely on other analgesic methods in clinical practice.

[0003] To alleviate postoperative pain, clinical practice typically employs intravenous analgesics, local infiltration anesthetics, or oral analgesics. Intravenous injection offers the fastest onset of action but is prone to systemic side effects and the risk of addiction; local infiltration anesthesia provides precise analgesia with fewer local side effects, but its duration of action is short and dosage control is difficult; oral medications are convenient but have a slow onset of action and may impose a gastrointestinal burden. All these methods have significant limitations; therefore, integrating analgesia directly into the suture becomes the ideal solution.

[0004] Currently, electrospun nanofibers can be used to prepare composite sutures: functional nanofibers are wrapped around a core yarn as a sheath to form a core-spun yarn. Based on this technology, researchers have attempted to prepare drug-loaded sutures. For example, patent application CN117531037A discloses a surgical suture composed of a porous drug-loaded nanofiber functional coating layer and a core yarn support layer. The drug is loaded in the porous sheath, and controlled drug release is achieved by using volatile oils to create pores. The core layer is a healing-promoting material. However, this porous drug-loaded structure has significant drawbacks: First, the porous structure has closed pores and a large specific surface area, leading to severe initial burst release of the drug and an inability to release it smoothly; second, the porous structure disrupts the compactness and mechanical integrity of the fiber body, resulting in a significant loss of suture strength; third, the drug is prone to recrystallization or inactivation when stored in the nanopores, resulting in poor long-term stability; fourth, the smooth porous surface has low friction with tissue, making it prone to suture slippage and displacement in humid environments, and is not suitable for tissues with high tension or soft and fragile tissues.

[0005] Therefore, there is an urgent need for a suture that can prevent initial drug release, maintain the mechanical integrity of the suture, prevent drug recrystallization or inactivation, and enhance surface friction to prevent suture slippage and displacement. Summary of the Invention

[0006] The purpose of this invention is to solve the problems in the prior art and provide a suture with immediate, continuous and long-lasting analgesic function and its preparation method.

[0007] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0008] A method for preparing a suture with immediate, continuous, and long-lasting analgesic function includes the following steps:

[0009] (a) Using elastic fibers in a stretched state as the receiving substrate, electrospinning is performed on them with an electrospinning solution containing analgesic drugs, and the stretching force on the elastic fibers is removed to obtain a yarn with a surface wrinkled topology.

[0010] (b) The yarn with the surface wrinkle topology is heat-set and cool-set in sequence to fix the surface wrinkle topology;

[0011] (c) Extract the elastic fibers from the yarn with a surface wrinkled topology to obtain a nano-yarn with a hollow structure;

[0012] (d) After impregnating the hollow nanofibers in a solution containing analgesic drugs, post-processing is performed to obtain sutures with immediate, continuous and long-lasting analgesic function.

[0013] The principle of this invention is as follows:

[0014] In step (a), after the stretching force on the elastic fiber is removed, the elastic fiber retracts, causing it to generate compressive stress and buckle, thereby obtaining a yarn with a surface wrinkled topology. This wrinkled topology forms an open surface groove structure, in which the drug is mainly loaded and released mainly through surface diffusion, which can avoid the initial burst release of the drug and achieve rapid onset of action. At the same time, the wrinkled topology does not destroy the compactness of the fiber body, and the mechanical integrity is maintained after drug loading. This open surface groove structure does not spatially restrict the analgesic drug molecules, making the analgesic drug molecules evenly distributed and less likely to reach the supersaturation critical concentration, thereby avoiding the recrystallization or inactivation of the analgesic drug molecules and maintaining long-term stability and effectiveness.

[0015] Step (b) permanently fixes the surface wrinkle topology through heat setting and cooling setting to prevent structural deformation during subsequent processing or use. At the same time, the surface wrinkle topology increases the specific surface area and friction between the suture and the tissue, preventing the suture knot from slipping and displacement in a humid environment.

[0016] Step (c) extracts the elastic fiber to obtain a nanofiber with a hollow structure. This hollow structure increases the drug storage space and connects with the surface wrinkled topology to form a multi-level release channel.

[0017] Step (d) involves impregnating the hollow nanofibers in a solution containing analgesic drugs and then performing post-treatment to load the analgesic drugs onto the hollow structures and folds, thus achieving secondary drug loading.

[0018] In the suture thus prepared, which has immediate, continuous and long-lasting analgesic functions, the drug loaded during electrospinning and the drug loaded during impregnation are released sequentially: the former provides immediate analgesia, and the latter provides continuous and long-lasting analgesia, thus achieving the function of immediate, continuous and long-lasting analgesia.

[0019] As a preferred technical solution:

[0020] The method for preparing a suture with immediate, continuous, and long-lasting analgesic function as described above allows for the use of elastic fibers made from natural rubber, recombinant elastin, synthetic biodegradable polyester materials such as poly(glycerol-sebate) ester (PGS), or bio-based thermoplastic elastomers such as bio-based polyurethane (Bio-TPU), which possess excellent elasticity. The stretching ratio of the elastic fibers in the stretched state is 100% to 250%, preferably 150% to 200%, and this parameter determines the size of the folds. When the stretching ratio exceeds 200% (e.g., 220%, 250%), although a folded topology can still be formed, excessively high recoil force may cause microcracks or local structural damage in the cortex, which in turn increases the cumulative release rate of the analgesic drug at various time points, especially in the initial stage. Therefore, the stretching ratio of the present invention is preferably controlled within the range of 150% to 200%, within which a more stable cumulative release curve can be obtained.

[0021] The method for preparing a suture with immediate, continuous and long-lasting analgesic function as described above, wherein the electrospinning solution containing analgesic drugs comprises 10wt%~25wt% analgesic drugs, 10wt%~25wt% polymeric materials and solvents;

[0022] The polymer materials are polylactic acid-glycolic acid copolymer (PLGA), polyvinyl alcohol (PVA), polycaprolactone (PCL), polyvinylidene fluoride (PVDF), chitosan, gelatin, or hyaluronic acid;

[0023] The solvent can be a mixture of dichloromethane and hexafluoroisopropanol.

[0024] The method for preparing a suture with immediate, continuous and long-lasting analgesic function as described above includes an electrospinning device comprising a core yarn unwinding motor, an unwinding roller, two needle devices, two syringes, a high-voltage power supply, and a collecting roller; the two needle devices are arranged opposite each other on both sides of the elastic fiber running path, the two syringes are respectively connected to the two needle devices, and the positive and negative terminals of the high-voltage power supply are respectively connected to the two needle devices.

[0025] The preparation method of the suture with immediate, continuous and long-lasting analgesic function as described above includes the following electrospinning process parameters: linear speed of the unwinding roller 1 mm / min, syringe injection speed 0.01~0.02 mL / min, rotation speed of the trumpet-shaped fiber collector 20~60 r / min, positive electrode working voltage of the high-voltage power supply 6~12 kV, negative electrode working voltage of the high-voltage power supply -6~-12 kV, and linear speed of the collecting roller 2.1~3.5 mm / min. The degree of stretching of the elastic fiber can be adjusted by adjusting the linear speed of the unwinding roller and the linear speed of the collecting roller. The stretching rate of the elastic fiber in the stretching state is = [(linear speed of the collecting roller - linear speed of the unwinding roller) / linear speed of the unwinding roller] × 100%.

[0026] The method for preparing a suture with immediate, continuous and long-lasting analgesic function as described above involves a heat setting temperature of 35~75℃, which aims to better eliminate the internal stress generated in the yarn cortex during the wrinkle formation process and better ensure the permanent fixation of the surface wrinkle topology; and a cooling setting temperature of 0~4℃, which aims to better ensure that the yarn cortex hardens and resists collapse.

[0027] As described above, a method for preparing a suture with immediate, continuous, and long-lasting analgesic function involves first soaking the hollow-structured nano-yarn in an ethanol-water solution (7:3 volume ratio of ethanol and water) before impregnating it with a solution containing analgesic drugs. Then, the hollow-structured nano-yarn is naturally air-dried. This step aims to remove any residual grease or processing impurities from the yarn surface, allowing ethanol molecules to adsorb onto the yarn surface and temporarily convert it from a hydrophobic to a hydrophilic state. This facilitates the rapid, low-resistance, bubble-free entry of the analgesic drug solution into the hollow cavity via capillary action, allowing it to penetrate and fill the troughs of the folds.

[0028] The method for preparing a suture with immediate, continuous and long-lasting analgesic function as described above involves impregnating hollow nanofibers in a solution containing analgesic drugs for 2 to 3 cycles to ensure that the analgesic drugs are fully impregnated into the hollow cavities and the troughs of the pleated topology; the post-treatment is vacuum drying at room temperature (25°C); the impregnation temperature is 25 to 60°C, and the impregnation time for a single cycle is 30 to 90 minutes.

[0029] The method for preparing a suture with immediate, continuous and long-lasting analgesic function as described above involves a solution containing analgesic drugs with a content of 5-15 wt%, and the solvent being an aqueous ethanol solution.

[0030] The method for preparing a suture with immediate, continuous and long-lasting analgesic function as described above, wherein all analgesic drugs are selected from at least one of ropivacaine, bupivacaine, tetracaine and ketoprofen, and ropivacaine may be base ropivacaine or ropivacaine hydrochloride.

[0031] The present invention also provides a suture with immediate, continuous and long-lasting analgesic function, which is prepared by the preparation method of a suture with immediate, continuous and long-lasting analgesic function as described in any of the preceding claims;

[0032] The cumulative release rates of sutures with immediate, continuous, and long-lasting analgesic functions in vitro in PBS (phosphate-buffered saline, pH 7.4, 37°C) were 7.49%–19.76% at 0.5 h, 11.94%–24.12% at 1 h, 17.44%–34.89% at 2 h, 23.53%–41.93% at 6 h, 29.75%–49.14% at 12 h, 38.69%–59.50% at 24 h, 50.46%–75.91% at 3 days, 68.46%–87.60% at 7 days, 81.34%–94.82% at 14 days, and 94.30%–98.63% at 21 days.

[0033] The suture with immediate, continuous and long-lasting analgesic function has a surface roughness of 2.5~8.0μm, a wet dynamic friction coefficient of 0.21~0.90, a maximum friction force of 0.43~1.81N, a breaking strength of 4.8~9.7N, a knot breaking strength (i.e., the breaking strength at the knot after the suture is tied) of 8.7~19.4N, and a displacement of 0.5~3.6mm after 200 cycles of loading in a humid environment.

[0034] Beneficial effects:

[0035] (1) The preparation method of the present invention uses elastic fibers in a stretched state as receiving substrates. After electrospinning, the stretching force is removed to form a surface wrinkled topology. The structure is then fixed by heat setting and cooling setting. The elastic fibers are extracted to obtain hollow nanofibers. Finally, the drug is loaded for secondary loading through impregnation. The above steps work together to make the drug loaded during electrospinning and the drug loaded during impregnation release in a gradient. The former provides immediate analgesia, and the latter provides continuous long-acting analgesia, thereby achieving both immediate and continuous long-acting analgesia for postoperative wounds.

[0036] (2) The preparation method of the present invention adopts a combination of surface wrinkled topology and hollow structure. The surface wrinkled topology increases the specific surface area and friction between the suture and the tissue, effectively preventing the suture knot from slipping and displacement in a humid environment. The hollow structure serves as an additional drug reservoir and is connected with the surface wrinkled topology to form a multi-level release channel, which increases the total drug load and achieves gradient release of peaks and troughs.

[0037] (3) The suture with immediate, continuous and long-lasting analgesic function of the present invention is prepared by the above preparation method. Its surface wrinkle topology is an open groove structure, which does not destroy the compactness of the fiber body. The mechanical integrity is maintained after drug loading. Moreover, the open groove structure avoids drug recrystallization or inactivation and maintains the long-term stability of the drug. At the same time, the suture has no initial burst release in in vitro release, the cumulative release rate is stable, and it has good breaking strength, knot breaking strength and resistance to cyclic loading displacement. Attached Figure Description

[0038] Figure 1 This is a schematic diagram of an electrospinning device. The dashed arrows represent the direction of fiber output in electrospinning, the circular arrows represent the rotation direction of the trumpet-shaped fiber collector, the horizontal solid arrows represent the running direction of the elastic fibers, and the vertical solid arrows represent the running direction of the stretched elastic fiber-coated nanofiber yarn (stretched elastic fiber-coated nanofiber yarn refers to the state in which the surface of the stretched elastic fiber has been coated with a nanofiber layer by electrospinning and is in the state before shrinkage).

[0039] Figure 2 This is a flowchart illustrating the preparation method of sutures with immediate, continuous, and long-lasting analgesic functions. The horizontal arrows represent the stretching direction of the elastic fibers, the vertical arrows represent the preparation process of the hollow nanofibers, and the dashed lines represent the positions of the elastic fibers.

[0040] Figure 3 yes Figure 2 Enlarged view of section I;

[0041] Figure 4 These are the cumulative analgesic drug release rate curves of the sutures prepared in Examples 1-4 and Examples 7-9;

[0042] Figure 5 This is the cumulative release rate curve of analgesic drug from the sutures prepared in Example 1, Comparative Example 1, and Comparative Example 2;

[0043] In the diagram, 1 is the core yarn unwinding motor, 2 is the unwinding roller, 3 is the yarn guiding device, 4 is the trumpet-shaped fiber collector, 5 is the first needle device, 6 is the second needle device, 7 is the first syringe, 8 is the second syringe, 9 is the positive terminal of the high-voltage power supply, 10 is the negative terminal of the high-voltage power supply, 11 is the collecting roller, and 12 is the collecting roller speed control device. Detailed Implementation

[0044] The present invention will be further described below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Furthermore, it should be understood that after reading the teachings of this invention, those skilled in the art can make various alterations or modifications to the invention, and these equivalent forms also fall within the scope defined by the appended claims.

[0045] The following are the test methods for the relevant performance indicators in each embodiment:

[0046] (1) Cumulative release rate

[0047] First, a standard curve for ropivacaine hydrochloride was established. Using a UV-Vis spectrophotometer (Shanghai Yuanxi Instrument Co., Ltd., model X-6, with a 1cm path length for the cuvettes), the test was performed according to the requirements of the UV-Vis spectrophotometry method in General Chapter 0401 of the 2025 edition of the Pharmacopoeia of the People's Republic of China. Specifically, 102.0 mg of ropivacaine hydrochloride standard (Aladdin, purity 98%, CAS No.: 84057-95-4) was accurately weighed. After purity correction, the actual content of ropivacaine hydrochloride was 100.0 mg. A stock solution with a concentration of 1000 μg / mL of ropivacaine hydrochloride was prepared using PBS as a solvent (PBS formulation: NaCl 8.0 g, KCl 0.2 g, Na2HPO4 1.44 g, KH2PO4 0.2 g). 0.24g was added to distilled water and brought to a final volume of 1000mL. After mixing thoroughly, the pH was adjusted to 7.4 using hydrochloric acid or sodium hydroxide at 37°C. Unless otherwise specified, all PBS used in this invention follows this formulation, and the operating temperature is set according to specific experimental requirements. Testing showed that the pH of this PBS at 25°C is approximately 7.43~7.44 (small changes in the pH of PBS have no substantial effect on the UV absorption of ropivacaine hydrochloride). This stock solution was then serially diluted to obtain a series of standard solutions of 50, 100, 200, 300, 500, and 800 μg / mL. Three parallel standard solutions were prepared for each concentration point and tested at 25°C. Using PBS as a reference blank, the absorbance values ​​of each standard solution were recorded at 262 nm, and the arithmetic mean was taken. The concentration was plotted on the x-axis (x, μg / mL), and the average absorbance on the y-axis. Linear fitting was performed using the least squares method to obtain the regression equation: y = 0.0050 + 0.0010x, R0 2 =0.9990;

[0048] Secondly, the ropivacaine hydrochloride release assay was performed using the static release method. Specifically, a 5.0 cm suture sample was weighed and placed in a release system containing 10 mL of PBS. The sample was then incubated in a 37°C constant-temperature shaker wrapped in aluminum foil to protect it from light. The shaker was used for horizontal reciprocating oscillation at a speed of 60 rpm. At preset time points (0.5 h, 1 h, 2 h, 6 h, 12 h, 24 h, 3 d, 7 d, 14 d, 21 d), 3 mL of the release solution was collected (at each time point, solids in the release system were avoided or filtered out to ensure the collected release solution remained clear). Simultaneously, an equal volume of preheated PBS (37°C) was added to correct for any dilution effect. After cooling the collected 3 mL of release solution to 25°C, it was analyzed using a UV-Vis spectrophotometer at 262 nm. At a wavelength of 25°C and with blank PBS as a reference, the absorbance of the released solution was measured at each time point, and the concentration of ropivacaine hydrochloride was calculated based on the standard curve. If the sample concentration exceeded the range of the standard curve, it was appropriately diluted with PBS before testing, and the dilution factor was recorded and included in the calculation. The release amount was calculated based on the standard curve, and the cumulative release rate was calculated using the following formula:

[0049] ; ;

[0050] In the formula, The current sampling number ( (Numbered in chronological order of sampling time).

[0051] For the first The concentration of ropivacaine hydrochloride in the release solution at the time of the first sampling is expressed in μg / mL.

[0052] The total volume of the release system (10 mL);

[0053] For the first The concentration of ropivacaine hydrochloride in the released solution at the time of the second sampling ( );

[0054] The volume of each sample taken is 3 mL.

[0055] As of the end of the The cumulative release of ropivacaine hydrochloride at each sampling time is expressed in μg, and its calculation takes into account the loss caused by multiple sampling.

[0056] The total load of ropivacaine hydrochloride in the suture sample ( Determination method: Take a 5.0 cm sample of the same batch of sutures, place it in 10 mL of PBS and sonicate at 25 °C until the ropivacaine hydrochloride in the suture sample is completely released and dissolved. After dissolution, centrifugation and filtration are not required. After standing, take the supernatant directly to measure the absorbance and calculate the total load of ropivacaine hydrochloride in the suture sample according to the standard curve (unit: μg).

[0057] Three parallel samples were made for each suture sample, and the arithmetic mean of the cumulative release rate at each time point was taken as the final result.

[0058] (2) Surface roughness (characterized by the arithmetic mean deviation of the profile Ra): The surface roughness profiler (Shenzhen Zhongtu Instrument Co., Ltd., model SJ5800-100) was used for testing in accordance with standards GB / T 10610-2009 and GB / T3505-2009. Measurement parameters: stylus tip curvature radius was 2μm, measuring force was 2mN, sampling length lr was 2.5mm, and evaluation length ln was 12.5mm (including 5 consecutive sampling lengths). The measurement direction was perpendicular to the suture axis (the arithmetic mean deviation Ra measured in this direction is the largest). Before measurement, the sample surface was gently wiped with a cotton swab soaked in anhydrous ethanol and allowed to air dry naturally at 25℃ and 50% relative humidity. The suture was fixed straight on the stage to avoid stretching. Three sutures were taken from each sample group, and five test points were evenly selected along the length of each suture (avoiding the two ends by 1cm). First, calculate the arithmetic mean of the profile arithmetic mean deviation Ra of 5 test points on each suture line, and use it as the representative value of the profile arithmetic mean deviation Ra of that suture line; then calculate the arithmetic mean of the representative values ​​of the profile arithmetic mean deviation Ra of the 3 suture lines, and use it as the final measurement result of the profile arithmetic mean deviation Ra of the group of suture lines.

[0059] (3) Wet dynamic friction coefficient: Referencing YY / T 1536-2017 "Standard Test Model for Evaluating the Sliding Performance of Non-Intravascular Catheters", GB / T 10006-2021 "Method for Determining the Coefficient of Friction of Plastic Films and Sheets" (Calculation Method Part) and ASTM D1894-14 (Principle of Friction Coefficient Calculation), the PMT-05 catheter sliding performance tester was used for testing. The test conditions were as follows: the abrasive material was a silicone sheet with a Shore A hardness of 55, the normal load was 3N, the test speed was 200mm / min, the traction distance was 200mm, and the sensor range did not exceed 10N. The wet environment was achieved by immersing the suture and the abrasive material in 37℃ physiological saline for 5min. The sodium chloride concentration in the physiological saline was 0.9% by mass and volume. The entire test was conducted in a water bath containing 37℃ physiological saline, with the liquid surface covering the suture. Three sutures were taken from each group, and five test points were evenly selected along the length of each suture (avoiding the two ends by 1 cm). The average force value within the sliding displacement range of 50 mm to 150 mm recorded by the instrument was taken as the average force value of the stable sliding segment at that test point. First, calculate the average force value of the stable sliding segment at 5 test points along each suture line. The arithmetic mean of the values ​​is used as the average force value of the stable sliding segment of the suture. Representative value; then calculate the average force value of the stable sliding segment of the three sutures. The arithmetic mean of the representative values ​​is used to calculate the wet dynamic friction coefficient of the suture group. :

[0060] ;

[0061] In the formula, The average force (N) of the stable sliding section. The normal load is 3 N.

[0062] (4) Maximum friction force: The test was conducted using a medical suture friction tester (Shanghai Xinxian Instrument Co., Ltd., model XF-1A). Specifically, the first suture (denoted as suture 1) with a length of 20cm was first knotted into a loop; then the second suture (denoted as suture 2) with a length of 20cm was passed through the loop formed by suture 1 and knotted into a loop, with suture 1 and suture 2 interlocked to form an interlocked structure; next, one end of the third suture (denoted as suture 3) with a length of 15cm was tied to a 20cN weight, and the other end was vertically clamped to the sensing clamp of the medical suture friction tester; the interlocked structure was placed on suture 3, and the interlocked structure was allowed to slide freely in the vertical direction. During the test, the interlocked structure moved vertically downward at a speed of 75mm / min, and the friction force curve between suture 3 and the interlocked structure was recorded. The peak friction force (maximum force value) was read from the friction force curve. Each type of suture was tested 5 times (using a new suture 1, suture 2, and suture 3 each time, for a total of 15 sutures). The arithmetic mean of the 5 peak friction forces was calculated as the maximum friction force (unit: cN) of that type of suture. The test was conducted at a temperature of 25℃ and a relative humidity of 50%±5%.

[0063] (5) Breaking strength: The test was conducted according to Appendix B of YY 1116-2020 "Absorbable Surgical Sutures" to evaluate the mechanical properties of the sutures. Specifically, a single knot was tied in the middle of the suture and tightened. The two ends of the suture were fixed in the upper and lower clamps of an electronic universal testing machine (Xieqiang Instrument Manufacturing (Shanghai) Co., Ltd., model CTM2050). The distance between the clamps (gauge length) was set to 100 mm, and the tensile speed was set to 200 mm / min. The suture was pulled to break at this tensile speed, and the maximum force value was recorded as the single-strand breaking strength value (unit: N). Five sutures were taken from each group, and each suture was tested once. The arithmetic mean of the five single-strand values ​​was calculated as the breaking strength of the suture group. All tests were conducted at a temperature of 25℃ and a relative humidity of 50%±5%.

[0064] (6) Knot breaking strength: The breaking strength test was conducted according to the method specified in Appendix B of YY 1116-2020 Absorbable Surgical Sutures. This test was used to evaluate the strength of the knot, i.e., whether the knot itself would slip or break after the suture was tied. Specifically, an electronic universal testing machine (Xieqiang Instrument Manufacturing (Shanghai) Co., Ltd., model CTM2050) was used for the test. Before the test, a 20cm length of the suture to be tested was taken and wrapped around a cylindrical iron clamp (15mm in diameter). Then, two surgical square knots were tied at both ends of the suture (each knot was wrapped twice and then tightened) to form a suture loop, ensuring that the knot was located in the middle of the cylinder. The suture was stretched at a constant speed of 50mm / min until it broke at the knot. The maximum tensile force was recorded as the knot breaking strength of the suture (unit: N). Five sutures were taken from each group, and each suture was tested once. The arithmetic mean of the knot breaking strength of these five tests was calculated, which is the final result of the knot breaking strength of the suture group. All tests were conducted in an environment with a temperature of 25℃ and a relative humidity of 50%±5%, and the sutures were equilibrated in this environment for 24 hours before the test.

[0065] (7) Cumulative residual displacement after 200 cycles of loading in a humid environment: The cumulative residual displacement was tested using an electronic universal testing machine (CTM2050, manufactured by Xieqiang Instruments (Shanghai) Co., Ltd.) to evaluate the fatigue resistance and anti-slipping performance of the suture knots. Before testing, the suture was immersed in PBS at 37°C for 3 minutes, and the surface liquid was gently wiped off after removal. The two ends of the suture with standard surgical knots were fixed to the winding fixture of the electronic universal testing machine. The initial gauge length was set to 120 mm, ensuring that the knot was in the center of the fixture and that the loading axis was aligned. The control mode was force control, the waveform was a sine wave, the frequency was 1 Hz, and the force range was 5 N to 50 N. The specific cycle method was as follows: loading from 0 N to 5 N (lower limit) at a rate of 0.5 N / s, then loading from 5 N to 50 N, and then unloading back to 5 N, which constituted a complete cycle. The waveform was symmetrical, and the force control accuracy was within ±0.5%. The sampling frequency was set to 200Hz, and the software accompanying the electronic universal testing machine synchronously recorded time, real-time force, and real-time displacement. The peak displacement of each cycle was defined as the displacement corresponding to the upper limit force of 50N, and the residual displacement was defined as the displacement when unloaded back to the lower limit force of 5N. Five independent suture samples were tested in each group (destructive testing, one test per suture), and the cumulative residual displacement at the end of 200 cycles was recorded, which is the final result of the cumulative residual displacement after 200 cycles of loading in a humid environment. PBS was continuously added during the cyclic loading process to maintain a humid environment.

[0066] Example 1

[0067] A method for preparing a suture with immediate, continuous, and long-lasting analgesic function, such as Figure 1 , Figure 2 and Figure 3 As shown, the specific steps are as follows:

[0068] (1) Raw material preparation

[0069] Elastic fiber: Thermoplastic polyurethane elastomer (TPU) monofilament, the linear density of the monofilament is 100D, and the manufacturer of the monofilament is Shengfang Special Fiber (Shanghai) Co., Ltd.

[0070] Polymer material: Polylactic acid-glycolic acid copolymer (PLGA), manufactured by Evonik Industries AG (Germany), brand name RESEROMER. ® RG 756 S (monomer molar ratio D,L-lactide:glycol = 75:25, ester-terminated, intrinsic viscosity 0.71~1.0 dL / g);

[0071] Dichloromethane;

[0072] Hexafluoroisopropanol;

[0073] Ethanol;

[0074] Water: Deionized water;

[0075] Analgesic drug: Ropivacaine hydrochloride, manufactured by Shanghai Yien Chemical Technology Co., Ltd., brand name Ron Reagent, catalog number R014284-25g;

[0076] (2) Preparation of electrospinning solution containing analgesic drugs

[0077] The polymer material and analgesic drug were placed in a spinning bottle, a solvent was added, and the mixture was stirred at 270 r / min for 5 hours. After stirring, the mixture was allowed to stand for 30 minutes to remove air bubbles, thus obtaining an electrospinning solution containing analgesic drug.

[0078] The components and contents of the electrospinning solution containing analgesic drugs are as follows: 25 wt% analgesic drugs, 25 wt% polymer materials and the balance solvent, which is a homogeneous mixture of dichloromethane and hexafluoroisopropanol in a volume ratio of 2:1.

[0079] (3) Electrospinning

[0080] like Figure 1 As shown, the electrospinning device includes a core yarn unwinding motor 1, an unwinding roller 2, a yarn guiding device 3, a trumpet-shaped fiber collector 4, a first needle device 5, a second needle device 6, a first syringe 7, a second syringe 8, a positive terminal of a high-voltage power supply 9, a negative terminal of a high-voltage power supply 10, a collecting roller 11, and a collecting roller speed regulating device 12.

[0081] The unwinding roller 2 is connected to the core yarn unwinding motor 1, which drives the unwinding roller 2 to rotate. The trumpet-shaped fiber collector 4 is set vertically below the yarn guiding device 3. The upper opening diameter of the trumpet-shaped fiber collector 4 is larger than the lower opening diameter. The elastic fiber is drawn out from the unwinding roller 2 and, after being guided by the yarn guiding device 3, runs vertically into the trumpet-shaped fiber collector 4. After the elastic fiber passes through the lower opening of the trumpet-shaped fiber collector 4, it continues to run vertically downward to the collecting roller 11. The collecting roller 11 is connected to the collecting roller speed regulating device 12, which regulates the rotation of the collecting roller 11.

[0082] The first needle device 5 and the second needle device 6 are arranged opposite each other on the left and right sides of the vertical running path of the elastic fiber. The midpoint of the line connecting the first needle device 5 and the second needle device 6 is located directly below the trumpet-shaped fiber collector 4. The positive terminal 9 and the negative terminal 10 of the high voltage power supply are connected to the first needle device 5 and the second needle device 6, respectively.

[0083] The prepared electrospinning solution containing analgesic drugs is loaded into the first syringe 7 and the second syringe 8 respectively. The first syringe 7 and the second syringe 8 are then connected to the first needle device 5 and the second needle device 6 respectively by threaded knobs. The first syringe 7 and the second syringe 8 are then pushed in. The rotation of the trumpet-shaped fiber collector 4 collects and twists the fibers sprayed from the first needle device 5 and the second needle device 6, and covers the outer peripheral surface of the elastic fiber, which serves as the receiving substrate. The distance between the first needle device 5 and the second needle device 6 is 25 cm, and the vertical distance between the line connecting the first needle device 5 and the second needle device 6 and the collecting roller 11 is 50 cm. The capacity of the first syringe 7 and the second syringe 8 is 10 mL.

[0084] During the spinning process, the linear speeds of the unwinding roller 2 and the collecting roller 11 are fixed. The difference in linear speed between the unwinding roller 2 and the collecting roller 11 will generate a constant stretching force on the elastic fiber, so that the elastic fiber is in a stretched state, forming a stretched elastic fiber covering nano yarn, which is then wound onto the collecting roller 11.

[0085] After winding, the collecting roller 11 is disassembled, transferred to a fume hood and placed at 23±2℃ for 4 hours to remove the residual solvent of the stretched elastic fiber-coated nano yarn, and the collecting roller 11 with the stretched elastic fiber-coated nano yarn is obtained.

[0086] The electrospinning process parameters are as follows: the linear speed of the unwinding roller 2 is 1 mm / min, the rotation speed of the trumpet-shaped fiber collector 4 is 40 r / min, the pushing speed of the first syringe 7 and the second syringe 8 is 0.018 mL / min, the working voltage of the positive terminal 9 of the high voltage power supply is 8.84 kV, the working voltage of the negative terminal 10 of the high voltage power supply is -8.45 kV, the linear speed of the collecting roller 11 is 2.4 mm / min, and the stretching rate of the elastic fiber in the stretching state is 140%. The above process parameters together determine the amount of nano-yarn coating on the surface of the stretching elastic fiber.

[0087] (4) The collecting roller 11 with the drawn elastic fiber-coated nano yarn is mounted on the yarn unwinding motor (the yarn unwinding motor is not shown in the figure). One end of the drawn elastic fiber-coated nano yarn on the collecting roller 11 is fixed manually. As the yarn unwinding motor unwinds at a uniform speed, the stretching force of the elastic fiber is removed, and a yarn with a surface wrinkled topology is obtained. The rotation speed of the yarn unwinding motor and the rotation speed of the core yarn unwinding motor 1 are kept consistent.

[0088] (5) Heat setting and cooling setting are performed on the yarn with surface wrinkle topology in sequence to fix the surface wrinkle topology; the heat setting temperature is 75℃ and the cooling setting temperature is 4℃.

[0089] (6) Extract the elastic fibers from the yarn with the surface wrinkled topology to obtain nano yarn with a hollow structure;

[0090] (7) The hollow nano-yarn is soaked in an ethanol-water solution composed of ethanol and water in a volume ratio of 7:3 and then air-dried. Soaking in the ethanol-water solution will not cause significant elution or loss of the analgesic drug loaded on the electrospinning, because the analgesic drug is wrapped inside the fiber by the polymer material during electrospinning and does not come into direct contact with the ethanol-water solution.

[0091] (8) The hollow nano-yarn that has been air-dried is immersed in a solution containing analgesic drugs. The immersion is carried out in 3 cycles, the immersion temperature is 25℃, and the immersion time for each cycle is 90min.

[0092] The components and contents of the solution containing analgesic drugs are as follows: 15 wt% analgesic drugs and the balance solvent, which is a homogeneous mixture of ethanol and water in a volume ratio of 7:3.

[0093] (9) The impregnated nano-yarn with hollow structure is vacuum dried at a temperature of 25°C, an absolute pressure of 0.01 MPa, and a drying time of 30 min to obtain a suture with immediate, continuous and long-lasting analgesic function.

[0094] The cumulative release rate curve of the prepared suture with immediate, continuous, and long-lasting analgesic function in in vitro PBS (pH=7.4, 37℃) is shown in the figure below. Figure 4 As shown, the cumulative release rate was 11.87% at 0.5h, 21.30% at 1h, 28.44% at 2h, 36.52% at 6h, 43.15% at 12h, 57.79% at 24h, 72.45% at 3d, 84.01% at 7d, 93.05% at 14d, and 97.11% at 21d.

[0095] The suture with immediate, continuous and long-lasting analgesic function has a surface roughness of 4.2 μm, a wet dynamic friction coefficient of 0.47, a maximum friction force of 1.04 N, a breaking strength of 8.3 N, a knot breaking strength of 15.9 N, and a displacement of 1.2 mm after 200 cycles of loading in a humid environment.

[0096] Comparative Example 1

[0097] A method for preparing a suture thread differs from Example 1 only in that: in step (3), the linear speed of the unwinding roller is 1 mm / min, the linear speed of the collecting roller is 1 mm / min, and the stretching rate of the elastic fiber is 0%, that is, unstretched elastic fiber is used.

[0098] The cumulative release rate curve of the analgesic drug from the prepared suture in PBS (pH=7.4, 37℃) in vitro is shown in the figure below. Figure 5 As shown, the cumulative release rate was 25.55% at 0.5h, 38.85% at 1h, 48.90% at 2h, 59.51% at 6h, 65.66% at 12h, 79.18% at 24h, 88.70% at 3d, 95.44% at 7d, 98.93% at 14d, and 99.10% at 21d.

[0099] The suture has a surface roughness of 0.5 μm, a wet dynamic friction coefficient of 0.14, a maximum friction force of 0.30 N, a breaking strength of 6.5 N, a knot breaking strength of 12.2 N, and a displacement of 5.0 mm after 200 cycles of loading in a humid environment.

[0100] Compared with Example 1, the analgesic drug in the suture of Comparative Example 1 showed a large release of analgesic drugs in the early stage, a significantly increased cumulative release rate over 6 hours, reduced surface roughness, reduced wet dynamic friction coefficient, reduced maximum friction force, decreased mechanical strength, and significantly increased displacement after 200 cycles of loading in a humid environment. This is because the only difference between Comparative Example 1 and Example 1 is whether or not stretching is applied to the elastic fiber core yarn. This difference leads to a comprehensive deterioration of Comparative Example 1 in several key performance dimensions: In terms of analgesic drug release, no stretching means that no compressive stress can be generated after the core yarn is pulled out, the cortex fibers do not buckle, and cannot form... The wrinkled topology results in the direct exposure of analgesics to the surface with a very short diffusion path, leading to a large release of analgesics in the early stages. This also results in a smooth surface with reduced surface roughness, which in turn leads to the absence of edge effects. The smooth surface cannot form a mechanical interlock with the mating material during sliding, resulting in a significant reduction in both the wet dynamic friction coefficient and the maximum friction force. In terms of mechanical strength, the absence of stretching means that the molecular chains are unoriented, the internal structure of the fiber is loose, and the breaking strength and knot breaking strength are reduced. In terms of anti-slip ability, the absence of wrinkles and low friction result in weak knot anchoring, making it easy to slip under cyclic loading, and the displacement increases after 200 cycles of loading.

[0101] Comparative Example 2

[0102] A method for preparing a suture thread, which differs from Example 1 only in that step (6) is omitted, and the nano-yarn with a hollow structure used in step (7) is replaced with the yarn with a surface wrinkled topology obtained in step (5), that is, the elastic fiber is no longer extracted.

[0103] The cumulative release rate curve of the analgesic drug from the prepared suture in PBS (pH=7.4, 37℃) in vitro is shown in the figure below. Figure 5 As shown, the cumulative release rate was 24.86% at 0.5h, 36.43% at 1h, 47.68% at 2h, 57.46% at 6h, 63.71% at 12h, 76.45% at 24h, 85.43% at 3d, 93.67% at 7d, 97.15% at 14d, and 98.73% at 21d.

[0104] The surface roughness of the suture is 4.1 μm, the wet dynamic friction coefficient is 0.37, the maximum friction force is 0.75 N, the breaking strength is 8.1 N, the knot breaking strength is 15.5 N, and the displacement after 200 cycles of loading in a humid environment is 1.3 mm.

[0105] Compared with Example 1, the surface roughness, wet dynamic friction coefficient, maximum friction force, breaking strength, knot breaking strength, and cyclic loading displacement of the suture in Comparative Example 2 did not change significantly. However, the cumulative release rate of analgesic drugs in the initial stage (e.g., 0.5h, 6h, and 24h) was significantly increased. This is because, in terms of analgesic drug release, not extracting elastic fibers means that the elastic fibers permanently occupy the center of the suture, and cannot form a hollow cavity as a "reservoir" for analgesic drugs. The analgesic drugs can only be distributed in the limited space of the skin folds, resulting in a decrease in the total drug load and a single release channel, which leads to a significant increase in the cumulative release rate of analgesic drugs in the initial stage.

[0106] Example 2

[0107] A method for preparing a suture with immediate, continuous, and long-lasting analgesic function, comprising the following specific steps:

[0108] (1) Raw material preparation

[0109] Elastic fiber: thermoplastic polyurethane elastomer monofilament, the linear density of the monofilament is 100D, and the manufacturer of the monofilament is Shengfang Special Fiber (Shanghai) Co., Ltd.

[0110] Polymer material: Polycaprolactone is manufactured by Shanghai Aladdin Biochemical Technology Co., Ltd. (Aladdin), product number P579406-5g. The number average molecular weight is 80,000~100,000 g / mol and the molecular weight distribution (PDI) is 1.5~2.0, as determined by gel permeation chromatography (GPC).

[0111] Dichloromethane;

[0112] Hexafluoroisopropanol;

[0113] Ethanol;

[0114] Water: Deionized water;

[0115] Analgesic drug: Ropivacaine hydrochloride, manufactured by Shanghai Yien Chemical Technology Co., Ltd., brand name Ron Reagent, catalog number R014284-25g;

[0116] (2) Preparation of electrospinning solution containing analgesic drugs

[0117] The polymer material and analgesic drug were placed in a spinning bottle, a solvent was added, and the mixture was stirred at 270 r / min for 5 hours. After stirring, the mixture was allowed to stand for 30 minutes to remove air bubbles, thus obtaining an electrospinning solution containing analgesic drug.

[0118] The components and contents of the electrospinning solution containing analgesic drugs are as follows: 20 wt% analgesic drugs, 21 wt% polymer materials and the balance solvent, which is a homogeneous mixture of dichloromethane and hexafluoroisopropanol in a volume ratio of 1:1.

[0119] (3) Electrospinning

[0120] The electrospinning apparatus and electrospinning process are the same as in Example 1, and a collection roller with nanofibers wrapped with stretched elastic fibers is obtained.

[0121] The electrospinning process parameters are as follows: the linear speed of the unwinding roller is 1 mm / min, the rotation speed of the trumpet-shaped fiber collector is 20 r / min, the pushing speed of both the first and second syringes is 0.015 mL / min, the positive terminal working voltage of the high-voltage power supply is 7.56 kV, the negative terminal working voltage of the high-voltage power supply is -7.04 kV, the linear speed of the collecting roller is 2.1 mm / min, and the draw ratio of the elastic fiber in the drawn state is 110%.

[0122] (4) The collecting roller with the drawn elastic fiber-coated nano yarn is installed on the yarn unwinding motor. One end of the drawn elastic fiber-coated nano yarn on the collecting roller is fixed manually. As the yarn unwinding motor unwinds at a uniform speed, the stretching force of the elastic fiber is removed. The speed of the yarn unwinding motor and the speed of the core yarn unwinding motor are kept consistent to obtain a yarn with a surface wrinkled topology.

[0123] (5) Heat setting and cooling setting are performed on the yarn with surface wrinkle topology in sequence to fix the surface wrinkle topology; the heat setting temperature is 55℃ and the cooling setting temperature is 2℃.

[0124] (6) Extract the elastic fibers from the yarn with the surface wrinkled topology to obtain nano yarn with a hollow structure;

[0125] (7) Soak the hollow nanofibers in an ethanol-water solution composed of ethanol and water in a volume ratio of 7:3, and then air dry them naturally.

[0126] (8) The hollow nano-yarn that has been air-dried is impregnated in a solution containing analgesic drugs. Three vacuum cycles are performed during impregnation. The impregnation temperature is 30°C and the impregnation time for each cycle is 60 min.

[0127] The components and contents of the solution containing analgesic drugs are as follows: 10 wt% analgesic drugs and the balance solvent, which is a homogeneous mixture of ethanol and water in a volume ratio of 7:3.

[0128] (9) The impregnated nano-yarn with hollow structure is vacuum dried at a temperature of 25°C, an absolute pressure of 0.01 MPa, and a drying time of 30 min to obtain a suture with immediate, continuous and long-lasting analgesic function.

[0129] The cumulative release rate of the prepared suture with immediate, continuous, and long-lasting analgesic function in in vitro PBS (pH=7.4, 37℃) is shown in the figure below. Figure 4 As shown, the cumulative release rate was 13.25% at 0.5h, 22.19% at 1h, 30.57% at 2h, 37.97% at 6h, 45.99% at 12h, 58.93% at 24h, 73.94% at 3d, 84.80% at 7d, 91.59% at 14d, and 96.67% at 21d.

[0130] The suture with immediate, continuous and long-lasting analgesic function has a surface roughness of 3.6 μm, a wet dynamic friction coefficient of 0.44, a maximum friction force of 0.80 N, a breaking strength of 8.1 N, a knot breaking strength of 15.7 N, and a displacement of 1.5 mm after 200 cycles of loading in a humid environment.

[0131] Example 3

[0132] A method for preparing a suture with immediate, continuous, and long-lasting analgesic function, comprising the following specific steps:

[0133] (1) Raw material preparation

[0134] Elastic fiber: thermoplastic polyurethane elastomer monofilament, the linear density of the monofilament is 100D, and the manufacturer of the monofilament is Shengfang Special Fiber (Shanghai) Co., Ltd.

[0135] Polymer material: Chitosan, manufactured by Shanghai Aladdin Biochemical Technology Co., Ltd. (Aladdin), product number C105799-25g, degree of deacetylation ≥95%, viscosity 100~200mPa·s (viscosity is determined according to the 2020 edition of the Pharmacopoeia of the People's Republic of China, Part IV, General Chapter 0633, Method III, by taking 1.0g of this product, adding 100mL of 1% glacial acetic acid solution, and measuring it at 20℃ using an NDJ-1 type rotary viscometer).

[0136] Dichloromethane;

[0137] Hexafluoroisopropanol;

[0138] Ethanol;

[0139] Water: Deionized water;

[0140] Analgesic drug: Ropivacaine hydrochloride, manufactured by Shanghai Yien Chemical Technology Co., Ltd., brand name Ron Reagent, catalog number R014284-25g;

[0141] (2) Preparation of electrospinning solution containing analgesic drugs

[0142] The polymer material and analgesic drug were placed in a spinning bottle, a solvent was added, and the mixture was stirred at 270 r / min for 5 hours. After stirring, the mixture was allowed to stand for 30 minutes to remove air bubbles, thus obtaining an electrospinning solution containing analgesic drug.

[0143] The components of the electrospinning solution containing analgesic drugs include 17.5 wt% analgesic drugs, 12 wt% polymeric materials, and the balance solvent, which is a homogeneous mixture of dichloromethane and hexafluoroisopropanol in a volume ratio of 1:2.

[0144] (3) Electrospinning

[0145] The electrospinning apparatus and electrospinning process are the same as in Example 1, and a collection roller with nanofibers wrapped with stretched elastic fibers is obtained.

[0146] The electrospinning process parameters are as follows: the linear speed of the unwinding roller is 1 mm / min, the rotation speed of the trumpet-shaped fiber collector is 50 r / min, the pushing speed of both the first and second syringes is 0.01 mL / min, the positive terminal working voltage of the high-voltage power supply is 6 kV, the negative terminal working voltage of the high-voltage power supply is -6 kV, the linear speed of the collecting roller is 3.2 mm / min, and the draw ratio of the elastic fiber in the drawn state is 220%.

[0147] (4) The collecting roller with the drawn elastic fiber-coated nano yarn is installed on the yarn unwinding motor. One end of the drawn elastic fiber-coated nano yarn on the collecting roller is fixed manually. As the yarn unwinding motor unwinds at a uniform speed, the stretching force of the elastic fiber is slowly removed. The speed of the yarn unwinding motor and the speed of the core yarn unwinding motor are kept consistent to obtain a yarn with a surface wrinkled topology.

[0148] (5) Heat setting and cooling setting are performed on the yarn with surface wrinkle topology in sequence to fix the surface wrinkle topology; the heat setting temperature is 60℃ and the cooling setting temperature is 1℃.

[0149] (6) Extract the elastic fibers from the yarn with the surface wrinkled topology to obtain nano yarn with a hollow structure;

[0150] (7) Soak the hollow nanofibers in an ethanol-water solution composed of ethanol and water in a volume ratio of 7:3, and then air dry them naturally.

[0151] (8) The hollow nano-yarn that has been air-dried is impregnated in a solution containing analgesic drugs. Two vacuum cycles are performed during impregnation. The impregnation temperature is 42.5℃ and the impregnation time for each cycle is 40min.

[0152] The components and contents of the solution containing analgesic drugs are as follows: 8 wt% analgesic drugs and the balance solvent, which is a homogeneous mixture of ethanol and water in a volume ratio of 7:3.

[0153] (9) The impregnated nano-yarn with hollow structure is vacuum dried at a temperature of 25°C, an absolute pressure of 0.01 MPa, and a drying time of 30 min to obtain a suture with immediate, continuous and long-lasting analgesic function.

[0154] The cumulative release rate of the prepared suture with immediate, continuous, and long-lasting analgesic function in in vitro PBS (pH=7.4, 37℃) is shown in the figure below. Figure 4 As shown, the cumulative release rate was 17.90% at 0.5h, 23.83% at 1h, 34.41% at 2h, 40.38% at 6h, 48.59% at 12h, 58.97% at 24h, 75.23% at 3d, 85.37% at 7d, 92.93% at 14d, and 95.74% at 21d.

[0155] The suture with immediate, continuous and long-lasting analgesic function has a surface roughness of 3.0 μm, a wet dynamic friction coefficient of 0.26, a maximum friction force of 0.55 N, a breaking strength of 6.0 N, a knot breaking strength of 10.8 N, and a displacement of 2.6 mm after 200 cycles of loading in a humid environment.

[0156] Example 4

[0157] A method for preparing a suture with immediate, continuous, and long-lasting analgesic function, comprising the following specific steps:

[0158] (1) Raw material preparation

[0159] Elastic fiber: thermoplastic polyurethane elastomer monofilament, the linear density of the monofilament is 100D, and the manufacturer of the monofilament is Shengfang Special Fiber (Shanghai) Co., Ltd.

[0160] Polymer material: Gelatin, manufactured by Shanghai Aladdin Biochemical Technology Co., Ltd. (Aladdin), catalog number G108396, pharmaceutical grade, type B gelatin (alkaline extraction, isoelectric point pI of 4.7~5.2), gel strength 240 Bloom g (tested according to GB6783-2013 standard by Bloom test, test conditions: 6.67% (w / v) gelatin solution, set at 10℃ for 17 hours), weight average molecular weight 10000~70000 g / mol (determined by gel permeation chromatography);

[0161] Dichloromethane;

[0162] Hexafluoroisopropanol;

[0163] Ethanol;

[0164] Water: Deionized water;

[0165] Analgesic drug: Ropivacaine hydrochloride, manufactured by Shanghai Yien Chemical Technology Co., Ltd., brand name Ron Reagent, catalog number R014284-25g;

[0166] (2) Preparation of electrospinning solution containing analgesic drugs

[0167] The polymer material and analgesic drug were placed in a spinning bottle, a solvent was added, and the mixture was stirred at 270 r / min for 5 hours. After stirring, the mixture was allowed to stand for 30 minutes to remove air bubbles, thus obtaining an electrospinning solution containing analgesic drug.

[0168] The components and contents of the electrospinning solution containing analgesic drugs are as follows: 10 wt% analgesic drugs, 10 wt% polymer materials and the balance solvent, which is a homogeneous mixture of dichloromethane and hexafluoroisopropanol in a volume ratio of 1:3.

[0169] (3) Electrospinning

[0170] The electrospinning apparatus and electrospinning process are the same as in Example 1, and a collection roller with nanofibers wrapped with stretched elastic fibers is obtained.

[0171] The electrospinning process parameters are as follows: the linear speed of the unwinding roller is 1 mm / min, the rotation speed of the trumpet-shaped fiber collector is 60 r / min, the pushing speed of both the first and second syringes is 0.02 mL / min, the positive working voltage of the high-voltage power supply is 12 kV, the negative working voltage of the high-voltage power supply is -12 kV, the linear speed of the collecting roller is 3.5 mm / min, and the draw ratio of the elastic fiber in the drawn state is 250%.

[0172] (4) The collecting roller with the drawn elastic fiber-coated nano yarn is installed on the yarn unwinding motor. One end of the drawn elastic fiber-coated nano yarn on the collecting roller is fixed manually. As the yarn unwinding motor unwinds at a uniform speed, the stretching force of the elastic fiber is slowly removed. The speed of the yarn unwinding motor and the speed of the core yarn unwinding motor are kept consistent to obtain a yarn with a surface wrinkled topology.

[0173] (5) Heat setting and cooling setting are performed on the yarn with surface wrinkle topology in sequence to fix the surface wrinkle topology; the heat setting temperature is 35℃ and the cooling setting temperature is 0℃.

[0174] (6) Extract the elastic fibers from the yarn with the surface wrinkled topology to obtain nano yarn with a hollow structure;

[0175] (7) Soak the hollow nanofibers in an ethanol-water solution composed of ethanol and water in a volume ratio of 7:3, and then air dry them naturally.

[0176] (8) The hollow nano-yarn after natural drying is impregnated in a solution containing analgesic drugs. Two vacuum cycles are performed during impregnation. The impregnation temperature is 60℃ and the impregnation time for each cycle is 30min.

[0177] The components and contents of the solution containing analgesic drugs are as follows: 5 wt% analgesic drugs and the balance solvent, which is a homogeneous mixture of ethanol and water in a volume ratio of 7:3.

[0178] (9) The impregnated nano-yarn with hollow structure is vacuum dried at a temperature of 25°C, an absolute pressure of 0.01 MPa, and a drying time of 30 min to obtain a suture with immediate, continuous and long-lasting analgesic function.

[0179] The cumulative release rate curve of the prepared suture with immediate, continuous, and long-lasting analgesic function in in vitro PBS (pH=7.4, 37℃) is shown in the figure below. Figure 4 As shown, the cumulative release rate was 19.76% at 0.5h, 24.12% at 1h, 33.98% at 2h, 41.93% at 6h, 48.72% at 12h, 59.50% at 24h, 75.91% at 3d, 87.60% at 7d, 94.82% at 14d, and 98.33% at 21d.

[0180] The suture with immediate, continuous and long-lasting analgesic function has a surface roughness of 2.8 μm, a wet dynamic friction coefficient of 0.21, a maximum friction force of 0.43 N, a breaking strength of 4.9 N, a knot breaking strength of 8.7 N, and a displacement of 3.6 mm after 200 cycles of loading in a humid environment.

[0181] Example 5

[0182] A method for preparing a suture with immediate, continuous, and long-lasting analgesic function differs from Example 1 only in that the linear speed of the collecting roller is changed so that the draw ratio is 100%, while the other parameters are exactly the same.

[0183] The sutures with immediate, continuous, and long-lasting analgesic effects showed the following cumulative release rates in in vitro PBS (pH=7.4, 37℃): 14.22% at 0.5h, 22.98% at 1h, 31.43% at 2h, 38.60% at 6h, 45.74% at 12h, 59.01% at 24h, 74.80% at 3d, 85.00% at 7d, 92.05% at 14d, and 96.00% at 21d.

[0184] The suture with immediate, continuous and long-lasting analgesic function has a surface roughness of 3.0 μm, a wet dynamic friction coefficient of 0.38, a maximum friction force of 0.76 N, a breaking strength of 7.71 N, a knot breaking strength of 14.3 N, and a displacement of 1.49 mm after 200 cycles of loading in a humid environment.

[0185] Example 6

[0186] A method for preparing a suture with immediate, continuous, and long-lasting analgesic function differs from Example 1 only in that the linear speed of the collecting roller is changed so that the draw ratio is 130%, while the other parameters are exactly the same.

[0187] The sutures with immediate, continuous, and long-lasting analgesic effects exhibited the following cumulative release rates in in vitro PBS (pH=7.4, 37℃): 12.49% at 0.5 h, 21.96% at 1 h, 29.54% at 2 h, 37.50% at 6 h, 45.48% at 12 h, 58.07% at 24 h, 72.92% at 3 days, 84.70% at 7 days, 91.22% at 14 days, and 97.91% at 21 days.

[0188] The suture with immediate, continuous and long-lasting analgesic function has a surface roughness of 4.0 μm, a wet dynamic friction coefficient of 0.45, a maximum friction force of 0.83 N, a breaking strength of 8.15 N, a knot breaking strength of 15.8 N, and a displacement of 1.4 mm after 200 cycles of loading in a humid environment.

[0189] Example 7

[0190] A method for preparing a suture with immediate, continuous, and long-lasting analgesic function differs from Example 1 only in that the linear speed of the collecting roller is changed so that the draw ratio is 150%, while the other parameters are exactly the same.

[0191] The cumulative release curve of the prepared suture with immediate, continuous, and long-lasting analgesic function in PBS (pH=7.4, 37℃) in vitro is shown in the figure below. Figure 4 As shown, the cumulative release rate was 8.63% at 0.5h, 14.75% at 1h, 20.48% at 2h, 27.19% at 6h, 33.20% at 12h, 42.13% at 24h, 56.57% at 3d, 68.46% at 7d, 88.15% at 14d, and 96.09% at 21d.

[0192] The suture with immediate, continuous and long-lasting analgesic function has a surface roughness of 7.1 μm, a wet dynamic friction coefficient of 0.84, a maximum friction force of 1.63 N, a breaking strength of 9.1 N, a knot breaking strength of 18.29 N, and a displacement of 0.72 mm after 200 cycles of loading in a humid environment.

[0193] Example 8

[0194] A method for preparing a suture with immediate, continuous, and long-lasting analgesic function differs from Example 1 only in that the linear speed of the collecting roller is changed so that the draw ratio is 175%, while the other parameters are exactly the same.

[0195] The cumulative release curve of the prepared suture with immediate, continuous, and long-lasting analgesic function in in vitro PBS (pH=7.4, 37℃) is shown below. Figure 4 As shown, the cumulative release rate was 7.50% at 0.5h, 12.79% at 1h, 17.44% at 2h, 23.53% at 6h, 30.85% at 12h, 39.37% at 24h, 50.46% at 3d, 68.91% at 7d, 82.40% at 14d, and 95.15% at 21d.

[0196] The suture with immediate, continuous and long-lasting analgesic function has a surface roughness of 8.0 μm, a wet dynamic friction coefficient of 0.9, a maximum friction force of 1.81 N, a breaking strength of 9.7 N, a knot breaking strength of 19.4 N, and a displacement of 0.5 mm after 200 cycles of loading in a humid environment.

[0197] Example 9

[0198] A method for preparing a suture with immediate, continuous, and long-lasting analgesic function differs from Example 1 only in that the linear speed of the collecting roller is changed so that the draw ratio is 200%, while the other parameters are exactly the same.

[0199] The cumulative release curve of the prepared suture with immediate, continuous, and long-lasting analgesic function in in vitro PBS (pH=7.4, 37℃) is shown below. Figure 4 As shown, the cumulative release rate was 7.49% at 0.5h, 11.94% at 1h, 17.85% at 2h, 25.46% at 6h, 29.75% at 12h, 38.69% at 24h, 50.73% at 3d, 70.17% at 7d, 81.34% at 14d, and 94.30% at 21d.

[0200] The suture with immediate, continuous and long-lasting analgesic function has a surface roughness of 7.5 μm, a wet dynamic friction coefficient of 0.82, a maximum friction force of 1.67 N, a breaking strength of 8.9 N, a knot breaking strength of 18.1 N, and a displacement of 0.73 mm after 200 cycles of loading in a humid environment.

[0201] Example 10

[0202] A method for preparing a suture with immediate, continuous, and long-lasting analgesic function differs from Example 1 only in that the linear speed of the collecting roller is changed so that the draw ratio is 220%, while the other parameters are exactly the same.

[0203] The sutures with immediate, continuous, and long-lasting analgesic effects exhibited the following cumulative release rates in in vitro PBS (pH=7.4, 37℃): 14.96% at 0.5 h, 23.13% at 1 h, 31.90% at 2 h, 39.57% at 6 h, 45.13% at 12 h, 58.13% at 24 h, 74.12% at 3 days, 85.64% at 7 days, 93.20% at 14 days, and 98.63% at 21 days.

[0204] The suture with immediate, continuous and long-lasting analgesic function has a surface roughness of 2.6 μm, a wet dynamic friction coefficient of 0.35, a maximum friction force of 0.60 N, a breaking strength of 7.2 N, a knot breaking strength of 13.6 N, and a displacement of 3.5 mm after 200 cycles of loading in a humid environment.

[0205] Example 11

[0206] A method for preparing a suture with immediate, continuous, and long-lasting analgesic function differs from Example 1 only in that the linear speed of the collecting roller is changed so that the draw ratio is 250%, while the other parameters are exactly the same.

[0207] The sutures with immediate, continuous, and long-lasting analgesic effects exhibited the following cumulative release rates in in vitro PBS (pH=7.4, 37℃): 18.00% at 0.5 h, 24.02% at 1 h, 34.89% at 2 h, 41.01% at 6 h, 49.14% at 12 h, 58.48% at 24 h, 75.36% at 3 days, 86.20% at 7 days, 94.17% at 14 days, and 98.40% at 21 days.

[0208] The suture with immediate, continuous and long-lasting analgesic function has a surface roughness of 2.5 μm, a wet dynamic friction coefficient of 0.34, a maximum friction force of 0.55 N, a breaking strength of 4.8 N, a knot breaking strength of 9.0 N, and a displacement of 3.6 mm after 200 cycles of loading in a humid environment.

Claims

1. A method for preparing a suture with immediate, continuous, and long-lasting analgesic function, characterized in that, Includes the following steps: (a) Using elastic fibers in a stretched state as the receiving substrate, electrospinning is performed on them with an electrospinning solution containing analgesic drugs, and the stretching force on the elastic fibers is removed to obtain a yarn with a surface wrinkled topology. (b) The yarn with the surface wrinkle topology is heat-set and cool-set in sequence to fix the surface wrinkle topology; (c) Extract the elastic fibers from the yarn with a surface wrinkled topology to obtain a nano-yarn with a hollow structure; (d) After impregnating the hollow nanofibers in a solution containing analgesic drugs, post-processing is performed to obtain sutures with immediate, continuous and long-lasting analgesic function.

2. The method for preparing a suture with immediate, continuous, and long-lasting analgesic function according to claim 1, characterized in that, The stretching rate of elastic fibers in a stretched state is 100%~250%.

3. The method for preparing a suture with immediate, continuous, and long-lasting analgesic function according to claim 1, characterized in that, Electrospinning solutions containing analgesic drugs include 10wt%~25wt% analgesic drugs, 10wt%~25wt% polymer materials and solvents; The polymer materials are polylactic acid-glycolic acid copolymer, polyvinyl alcohol, polycaprolactone, polyvinylidene fluoride, chitosan, gelatin or hyaluronic acid.

4. The method for preparing a suture with immediate, continuous, and long-lasting analgesic function according to claim 1, characterized in that, The device used for electrospinning includes a core yarn unwinding motor, an unwinding roller, two needle devices, two syringes, a high-voltage power supply, and a collecting roller. The two needle devices are arranged opposite each other on both sides of the elastic fiber running path. The two syringes are connected to the two needle devices respectively. The positive and negative terminals of the high-voltage power supply are connected to the two needle devices respectively.

5. A method for preparing a suture with immediate, continuous, and long-lasting analgesic function according to claim 4, characterized in that, The process parameters for electrospinning include: the linear speed of the unwinding roller is 1 mm / min, the rotation speed of the trumpet-shaped fiber collector is 20~60 r / min, the syringe push speed is 0.01~0.02 mL / min, the positive working voltage of the high voltage power supply is 6~12 kV, the negative working voltage of the high voltage power supply is -6~-12 kV, and the linear speed of the collecting roller is 2.1~3.5 mm / min.

6. The method for preparing a suture with immediate, continuous, and long-lasting analgesic function according to claim 1, characterized in that, The heat setting temperature is 35~75℃, and the cooling setting temperature is 0~4℃.

7. The method for preparing a suture with immediate, continuous, and long-lasting analgesic function according to claim 1, characterized in that, When the hollow nanofibers are impregnated in a solution containing analgesic drugs, the process is repeated 2 to 3 times; the impregnation temperature is 25 to 60°C, and the impregnation time for each cycle is 30 to 90 minutes.

8. A method for preparing a suture with immediate, continuous, and long-lasting analgesic function according to claim 1, characterized in that, The analgesic drug content in the solution is 5-15 wt%.

9. A method for preparing a suture with immediate, continuous, and long-lasting analgesic function according to claim 1, characterized in that, All analgesics are selected from at least one of ropivacaine, bupivacaine, tetracaine, and ketoprofen.

10. A suture with immediate, continuous, and long-lasting analgesic function, characterized in that, The suture is prepared using the method for preparing a suture with immediate, continuous and long-lasting analgesic function as described in any one of claims 1 to 9; The cumulative release rates of sutures with immediate, continuous, and long-lasting analgesic functions in vitro in PBS were 7.49%–19.76% at 0.5 h, 11.94%–24.12% at 1 h, 17.44%–34.89% at 2 h, 23.53%–41.93% at 6 h, 29.75%–49.14% at 12 h, 38.69%–59.50% at 24 h, 50.46%–75.91% at 3 days, 68.46%–87.60% at 7 days, 81.34%–94.82% at 14 days, and 94.30%–98.63% at 21 days. The suture with immediate, continuous and long-lasting analgesic function has a surface roughness of 2.5~8.0μm, a wet dynamic friction coefficient of 0.21~0.90, a maximum friction force of 0.43~1.81N, a breaking strength of 4.8~9.7N, a knot breaking strength of 8.7~19.4N, and a displacement of 0.5~3.6mm after 200 cycles of loading in a humid environment.

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