A multifunctional analgesic suture and its preparation method and application

Abstract

The present invention discloses a multifunctional analgesic suture and its preparation method and application. The covalent polymer polycaprolactone is used as a material, and the local anesthetic drug ropivacaine is wrapped. The suture fiber is based on a microfluidic platform, and the cured polycaprolactone fiber suture with a porous structure is made by a microfluidic solution extraction method. Due to the characteristics of solution extraction during the curing process, ropivacaine smoothly enters the polycaprolactone suture and fills the pores of the suture. The suture has excellent mechanical properties and a drug sustained release function of up to 3 days. Suturing operations such as pulling and knotting can be performed, and the thickness and pore size of the fiber can be finely changed by adjusting the solution concentration, microfluidic parameters, etc., so that the fiber mechanical properties and drug release rate can be regulated. The preparation method of the present invention has the advantages of being reusable, low cost, easy to operate, convenient and reliable.

Description

Technical Field

[0001] The invention belongs to the field of biomaterials, and in particular relates to a multifunctional analgesic suture thread and a preparation method and application thereof. Background Art

[0002] Sutures are ubiquitous fibrous materials used in surgical procedures for tissue layer fixation, wound closure, and vascular ligation. Although they can effectively approximate wound edges, they are insufficient in addressing pain, infection, and other issues that may hinder wound healing. Postoperative incision pain lasting for more than 72 hours will delay functional recovery, increase the risk of complications, and affect the patient's quality of life. Currently, the main treatments for postoperative pain include intravenous analgesia and local injection of local anesthetics (LA) at the surgical site. The former activates pain-related receptors such as opioids or COX receptors through systemic administration, inhibits the upward conduction of pain signals in the central nervous system pathway, or reduces the synthesis of prostaglandins PGE2 in the peripheral nervous system to achieve analgesia; the latter reversibly inhibits nerve conduction and thus relieves pain by binding to voltage-gated sodium channels (Na v) on the plasma membrane of peripheral nerves. Although these methods all have certain analgesic effects, systemic administration can cause side effects such as respiratory depression, central depression, gastrointestinal reactions, and addiction tendency, while local injection analgesia has a short duration. Therefore, there is an urgent need to explore a safe and long-lasting wound suture analgesia strategy.

[0003] The encapsulation of narcotic analgesics in functional microfibers and their application in postoperative analgesia are less common. The harsh forming conditions required for current commercial sutures, such as high temperature conditions, have an adverse effect on drug loading, and high temperature can lead to degradation and destruction of thermally unstable drugs. Summary of the invention

[0004] Purpose of the invention: The technical problem to be solved by the present invention is to provide a method for preparing a multifunctional analgesic suture in view of the deficiencies in the prior art, so as to solve the shortcomings of the traditional suture itself that lacks therapeutic function and has a short efficacy of local anesthetic drugs.

[0005] In order to solve the above technical problems, the technical solution adopted by the present invention is as follows:

[0006] A method for preparing a multifunctional analgesic suture comprises the following steps:

[0007] (1) coaxially nesting the inner phase capillary in the outer phase capillary to construct a microchannel kit of a microfluidic chip;

[0008] (2) preparing a fiber precursor solution containing polycaprolactone and analgesic drugs as an inner core liquid, and a continuous phase solution as an outer sheath liquid;

[0009] (3) The inner phase core liquid and the outer phase sheath liquid configured in step (2) are simultaneously and continuously injected into the microchannel kit of the microfluidic chip in step (1), and the inner phase solution solute is solidified in the microchannel through the extraction effect of the outer phase sheath liquid on the inner phase core liquid solvent to obtain a continuous solid fiber.

[0010] Specifically, in step (1), the inner phase capillary is a glass capillary with a diameter of 100 μm to 300 μm; and the outer phase capillary is a glass capillary with a diameter of 580 to 750 μm.

[0011] Specifically, the microfluidic chip uses cylindrical glass capillaries with smaller inner diameter and larger inner diameter (World Precision Instruments, Sarasota, USA) as the microchannels of the inner phase and the outer phase, respectively. The inner phase capillary is coaxially nested in the outer phase capillary to obtain a microchannel chip kit (such as Figure 1 The specific steps are as follows: coaxially nest the core liquid glass capillary and the sheath liquid glass capillary and fix them on the glass slide with AB glue; align the center of the pin plug bottom and the entrance of the inner and outer phase glass capillary respectively, and pay attention to the fit between the groove and the glass tube; finally, use a large amount of AB glue to seal the connection between the dispensing needle and the glass slide. Repeatedly wash with anhydrous ethanol and ultrapure water to obtain a microchannel chip.

[0012] Specifically, in step (2), the solutes of the inner phase core liquid are polycaprolactone (PCL) and analgesics; in the inner phase core liquid, the mass concentration of polycaprolactone is 6% to 10%, and the mass concentration of the analgesics is 5% to 10%.

[0013] Specifically, the analgesic drug is an aminoamide local anesthetic, preferably ropivacaine; the solvent of the inner phase core liquid is any one of N,N-dimethylformamide, dimethyl sulfoxide, and 2,2,2-trifluoroethanol, preferably N,N-dimethylformamide.

[0014] Specifically, in step (2), the solute of the external sheath liquid is polyethylene glycol, and the solvent of the external sheath liquid is deionized water (ddH2O); in the external sheath liquid, the mass concentration of polyethylene glycol ester is 6% to 8%.

[0015] Specifically, in step (3), the flow rates of the outer phase sheath liquid and the inner phase core liquid are controlled to be 100:50 μL / min to 500:50 μL / min.

[0016] Specifically, in step (3), the inner phase solution solute is solidified in the microchannel of the microfluidic chip at room temperature, and the outer phase sheath liquid is also used as a room temperature water bath liquid for collecting the solid fibers.

[0017] In the present invention, microfluidic spinning technology has many advantages, such as: it is universal in the selection of solutions and encapsulated additives; the microchannel can handle most fluids; and it avoids the restrictions of other technical conditions, such as avoiding high temperature requirements (high temperature will cause degradation of thermally unstable drugs), etc. By using this method, microfibers with various functions can be produced, such as microfibers with controlled drug delivery functions, and microfibers used as tissue engineering scaffolds for cell encapsulation, fixation and proliferation.

[0018] Polycaprolactone has excellent biocompatibility, degradability and excellent mechanical properties, which can meet the needs of drug delivery and suture preparation. Ropivacaine is an aminoamide local anesthetic drug. Due to its lipophilicity and hydrophobicity and mild coagulation mode, it is easy to achieve the purpose of encapsulation in polycaprolactone during the spinning process. Finally, using the unique capabilities of microfluidics, continuous fibers with a wide range of mechanical properties can be manufactured by changing the microfluidic channel size, PCL concentration, and the flow rate ratio of the sheath and core fluids.

[0019] Furthermore, the multifunctional analgesic suture prepared by the above preparation method is also within the protection scope required by the present invention.

[0020] Specifically, the outer part of the suture thread of the present invention is a biocompatible and degradable polymer material, and the inner part is wrapped with analgesic drugs. The polycaprolactone fiber is loaded with local anesthetic drugs and can be slowly released, and the mechanical properties of the fiber can meet the requirements of wound suture.

[0021] Furthermore, the present invention also claims to protect the use of the multifunctional analgesic suture thread in suturing biological skin and deep tissue.

[0022] Beneficial effects:

[0023] (1) The multifunctional analgesic suture of the present invention can wrap local anesthetic drugs, achieve drug sustained release, prolong the analgesic duration of the drugs, and has strong practicality. It can suture the skin and deep tissues, realizing a surgical suture that integrates analgesia and suture functions.

[0024] (2) The drug-loaded microfibers obtained by the microfluidic spinning technology of the present invention have the mechanical strength required for suturing. Microfluidics can process covalently bonded polycaprolactone (PCL). Polycaprolactone has excellent biocompatibility, degradability and excellent mechanical properties, and can meet the needs of drug delivery and suture preparation at the same time. Ropivacaine is an aminoamide local anesthetic drug. Due to its lipophilicity and hydrophobicity and mild coagulation mode, it is easy to achieve the purpose of encapsulation in polycaprolactone during the spinning process. Finally, the unique ability of microfluidics is used to manufacture continuous fibers with a wide range of mechanical properties by changing the microfluidic channel size, PCL concentration, and the flow rate ratio of the sheath layer and the core layer fluid. At the same time, the preparation method is simple, easy to operate, low-cost, does not require very high technical requirements, and it is easy to control the morphology and properties of the fiber. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] The present invention will be further described in detail below in conjunction with the accompanying drawings and specific embodiments, and the above and / or other advantages of the present invention will become more clear.

[0026] Figure 1 Actual photo (A) and schematic diagram (B) of the microfluidic microchannel chip.

[0027] Figure 2 Stereomicroscope images and digital photographs of sutures.

[0028] Figure 3 Application of multifunctional analgesic sutures.

[0029] Figure 4 The morphology of the sutures prepared with different flow rate ratios. Electron microscope images of the flow rate ratio of 100:50 (A) and 500:50 (B). DETAILED DESCRIPTION

[0030] The present invention can be better understood with reference to the following examples.

[0031] The preparation method of the multifunctional analgesic suture of the present invention comprises the following steps:

[0032] (1) Preparation steps of microfluidic microchannel chip:

[0033] The microfluidic chip uses cylindrical glass capillaries with smaller inner diameter and larger inner diameter (World Precision Instruments, Sarasota, USA) as the microchannels of the inner phase and the outer phase, respectively. The inner phase capillary is coaxially nested in the outer phase capillary to obtain a microchannel chip kit (such as Figure 1The specific steps are as follows: coaxially nest the core liquid glass capillary and the sheath liquid glass capillary and fix them on the glass slide with AB glue; align the center of the pin plug bottom and the entrance of the inner and outer phase glass capillary respectively, and pay attention to the fit between the groove and the glass tube; finally, use a large amount of AB glue to seal the connection between the dispensing needle and the glass slide. Repeatedly wash with anhydrous ethanol and ultrapure water to obtain a microchannel chip.

[0034] (2) Preparation steps of the main solution:

[0035] Prepare fiber precursor solution and continuous phase solution as inner phase solution and outer phase solution respectively. The inner phase solution solute is polycaprolactone (PCL, Mn=230,000) and ropivacaine, the inner phase solution solvent is N,N-dimethylformamide (DMF), the outer phase solution solute is polyethylene glycol, and the outer phase solution solvent is deionized water (ddH2O); wherein the outer phase sheath solution is also used as a water bath for collecting solid fibers. Prepare the solution at room temperature.

[0036] (3) Preparation steps of multifunctional analgesic suture

[0037] The prepared fluid is introduced into the injection pump of the microchannel, and the internal phase liquid solute is solidified in the glass capillary microchannel through the extraction of the external phase aqueous solution and the internal phase aqueous solvent to obtain a continuous solid fiber suture (such as Figure 2 As shown). The specific steps are: using a dual-drive syringe pump, the core liquid and the sheath liquid are introduced into the microchannel at the same time; the core fluid enters the channel through the needle opening connected to the inner phase capillary at the upper end, while the sheath fluid enters through the needle opening connected to the outer phase capillary at the lower end. The shear force between the core liquid and the sheath liquid dynamically concentrates the core liquid fluid in the center of the microchannel, and the shear force arranges the polymer chains along the final fiber flow direction. Here, solvent extraction is a phase inversion process: the solution in the core liquid is replaced by the solution of the sheath liquid, and the solute is insoluble in the sheath liquid, and they will solidify into fibers downstream of the channel; a solute of appropriate concentration is added to the sheath liquid to achieve a viscosity that matches the viscosity of the core liquid, so that the sheath liquid and the bath liquid act on the core liquid. The sheath liquid shear force is concentrated; during the entire process, the channel is placed vertically, and the produced fibers directly enter the water bath. The fibers are stable in the water bath and are easy to handle and collect, and finally a suture that can be sutured is obtained (such as Figure 3 ).

[0038] According to the above-mentioned microchannel chip preparation method, the inner glass capillary diameter is selected to be 100 μm to 300 μm, the outer glass capillary diameter is selected to be 580 to 750 μm, and the microchannel chip kit is made by nesting three combinations of 100-580, 100-750 and 300-750. The suture fiber produced by the device with the inner diameter combination of 100-750 has good mechanical properties and suitable fiber diameter size, and the maximum breaking force is obtained by testing the tensile force with a universal testing machine.

[0039] According to the above-mentioned method for preparing the main solution of the multifunctional analgesic suture, the concentration of polycaprolactone in the inner phase liquid is 6% to 10%, the concentration of ropivacaine is 5% to 10%, and the concentration of polyethylene glycol ester in the outer phase liquid is 6% to 8%. It is characterized in that the multifunctional analgesic suture can change the thickness of the suture and the pores on the suture by adjusting the solute concentration of the inner phase liquid. Under the conditions of a 100-750 combined device and a controlled flow rate of 100:50 μL / min, the 10% concentration of polycaprolactone produces a suture fiber with a diameter of 230.16±5.23 μm and a fiber surface pore diameter of 1.12±0.37 μm.

[0040] According to the above main easy preparation method, the concentration of polycaprolactone in the internal phase liquid is 6% to 10%, the concentration of ropivacaine is 5% to 10%, and the concentration of polyethylene glycol ester in the external phase liquid is 6% to 8%. The suture can change the analgesic efficacy and duration by adjusting the solute concentration of the internal phase liquid, and the mechanical withdrawal threshold of the plantar of mice with incision pain using this multifunctional labor pain suture is measured.

[0041] Example 1

[0042] (1) Preparation steps of microfluidic microchannel chip:

[0043] The microfluidic chip uses cylindrical glass capillaries with smaller and larger inner diameters (World Precision Instruments, Sarasota, USA) as microchannels for the inner and outer phases, respectively. The inner phase capillary is coaxially nested in the outer phase capillary to obtain a microchannel chip kit. The diameter of the inner phase glass capillary is 100 μm, and the diameter of the outer phase glass capillary is 750 μm. The specific steps are: coaxially nest the core liquid glass capillary and the sheath liquid glass capillary and fix them on the glass slide with AB glue; align the center of the bottom of the needle plug with the entrance of the inner and outer phase glass capillaries, respectively, and pay attention to the fit of the groove with the glass tube; finally, use a large amount of AB glue to seal the connection between the dispensing needle and the glass slide. Figure 1 The microchannel chip was obtained by repeated washing with anhydrous ethanol and ultrapure water.

[0044] (2) Preparation steps of inner phase liquid and outer phase liquid:

[0045] Prepare fiber precursor solution and continuous phase solution as inner phase solution and outer phase solution respectively. The inner phase solution solute is polycaprolactone (PCL, Mn=230,000) and ropivacaine, the inner phase solution solvent is N,N-dimethylformamide (DMF), the outer phase solution solute is polyethylene glycol, and the outer phase solution solvent is deionized water (ddH2O); the concentration of polycaprolactone in the inner phase solution is 10%, the concentration of ropivacaine is 5%, and the concentration of polyethylene glycol ester in the outer phase solution is 6% to 8%. The outer phase sheath solution is also used as a water bath for collecting solid fibers. Prepare the solution at room temperature.

[0046] (3) Preparation steps of multifunctional analgesic suture

[0047] The prepared fluid is introduced into the injection pump of the microchannel, and the internal phase liquid solute is solidified in the glass capillary microchannel through the extraction of the external phase aqueous solution and the internal phase aqueous solvent to obtain a continuous solid fiber suture. The specific steps are: using a dual-drive injection pump, the core liquid and the sheath liquid are introduced into the microchannel at the same time. The core fluid enters the channel through the needle opening connected to the internal phase capillary at the upper end, while the sheath fluid enters the needle opening connected to the external phase capillary at the lower end; the shear force between the core liquid and the sheath liquid dynamically concentrates the core liquid fluid in the center of the microchannel, and the shear force arranges the polymer chain along the final fiber flow direction. Here, solvent extraction is the process of phase inversion: the solution in the core liquid is replaced by the solution of the sheath liquid, and the solute is not dissolved in the sheath liquid. They will solidify into fibers downstream of the channel; during the whole process, the channel is placed vertically, and the generated fibers directly enter the water bath. The fibers are stable in the water bath and easy to handle and collect. The pumping parameters of the microfluidic injection pump are 50μL / min for the internal phase liquid and 100μL / min for the external phase liquid. The fiber diameter produced by this pumping parameter is 230.16±5.23μm, the pore diameter on the fiber is 1.12±0.37μm, and the number of pores is large; the maximum breaking force is 0.289±0.01 Newton. The fiber analgesic lasts for up to 3 days, and the pain threshold on the third day is 75.18±16.85% of the baseline value. Figure 4 -A.

[0048] Example 2

[0049] (1) Preparation steps of microfluidic microchannel chip:

[0050] The microfluidic chip uses cylindrical glass capillaries with smaller and larger inner diameters (World Precision Instruments, Sarasota, USA) as the microchannels of the inner phase and outer phase, respectively. The inner phase capillary is coaxially nested in the outer phase capillary to obtain a microchannel chip kit. The diameter of the inner phase glass capillary is selected to be 100 μm, and the diameter of the outer phase glass capillary is selected to be 750 μm. The specific steps are: coaxially nest the core liquid glass capillary and the sheath liquid glass capillary and fix them on the slide with AB glue; align the center of the bottom of the needle plug and the entrance of the inner and outer phase glass capillaries respectively, and pay attention to the fit of the groove and the glass tube; finally, use a large amount of AB glue to seal the connection between the dispensing needle and the slide. Repeatedly wash with anhydrous ethanol and ultrapure water to obtain a microchannel chip.

[0051] (2) Preparation steps of inner phase liquid and outer phase liquid:

[0052] Prepare fiber precursor solution and continuous phase solution as inner phase solution and outer phase solution respectively. The inner phase solution solute is polycaprolactone (PCL, Mn=230,000) and ropivacaine, the inner phase solution solvent is N,N-dimethylformamide (DMF), the outer phase solution solute is polyethylene glycol, and the outer phase solution solvent is deionized water (ddH2O); the concentration of polycaprolactone in the inner phase solution is 10%, the concentration of ropivacaine is 10%, and the concentration of polyethylene glycol ester in the outer phase solution is 6% to 8%. The outer phase sheath solution is also used as a water bath for collecting solid fibers. Prepare the solution at room temperature.

[0053] (3) Preparation steps of multifunctional analgesic suture

[0054] The formulated fluid is introduced into the syringe pump of the microchannel, and the solute of the internal phase liquid is solidified in the glass capillary microchannel through the extraction of the external phase aqueous solution and the internal phase aqueous solvent to obtain a continuous solid fiber suture. Using a dual-drive syringe pump, the core liquid and the sheath liquid are introduced into the microchannel at the same time. The core fluid enters the channel through the needle opening connected to the internal phase capillary at the upper end, while the sheath fluid enters the needle opening connected to the external phase capillary at the lower end. The shear force between the core liquid and the sheath liquid dynamically concentrates the core liquid fluid in the center of the microchannel, and the shear force arranges the polymer chains along the final fiber flow direction. Here, solvent extraction is the process of phase inversion: the solution in the core liquid is replaced by the solution of the sheath liquid, and the solute is not dissolved in the sheath liquid. They will solidify into fibers downstream of the channel. During the whole process, the channel is placed vertically, and the produced fibers directly enter the water bath. The fibers are stable in the water bath and easy to handle and collect. The pumping parameters of the microfluidic syringe pump are 50μL / min for the internal phase liquid and 100μL / min for the external phase liquid. The fiber diameter, pore size and mechanical properties produced by this pumping parameter were similar to those in Example 1, but the analgesic duration was as long as 4 days, and the pain threshold on the 3rd day was 97.86±22.68% of the baseline value.

[0055] Example 3

[0056] (1) Preparation steps of microfluidic microchannel chip:

[0057] The microfluidic chip uses cylindrical glass capillaries with smaller and larger inner diameters (World Precision Instruments, Sarasota, USA) as the microchannels of the inner phase and outer phase, respectively. The inner phase capillary is coaxially nested in the outer phase capillary to obtain a microchannel chip kit. The diameter of the inner phase glass capillary is selected to be 100 μm, and the diameter of the outer phase glass capillary is selected to be 750 μm. The specific steps are: coaxially nest the core liquid glass capillary and the sheath liquid glass capillary and fix them on the slide with AB glue; align the center of the bottom of the needle plug and the entrance of the inner and outer phase glass capillaries respectively, and pay attention to the fit of the groove and the glass tube; finally, use a large amount of AB glue to seal the connection between the dispensing needle and the slide. Repeatedly wash with anhydrous ethanol and ultrapure water to obtain a microchannel chip.

[0058] (2) Preparation steps of inner phase liquid and outer phase liquid:

[0059] Prepare fiber precursor solution and continuous phase solution as inner phase solution and outer phase solution respectively. The inner phase solution solute is polycaprolactone (PCL, Mn=230,000) and ropivacaine, the inner phase solution solvent is N,N-dimethylformamide (DMF), the outer phase solution solute is polyethylene glycol, and the outer phase solution solvent is deionized water (ddH2O); the concentration of polycaprolactone in the inner phase solution is 10%, the concentration of ropivacaine is 10%, and the concentration of polyethylene glycol ester in the outer phase solution is 6% to 8%. The outer phase sheath solution is also used as a water bath for collecting solid fibers. Prepare the solution at room temperature.

[0060] (3) Preparation steps of multifunctional analgesic suture

[0061] The formulated fluid is introduced into the syringe pump of the microchannel, and the solute of the internal phase liquid is solidified in the glass capillary microchannel through the extraction of the external phase aqueous solution and the internal phase aqueous solvent to obtain a continuous solid fiber suture. Using a dual-drive syringe pump, the core liquid and the sheath liquid are introduced into the microchannel at the same time. The core fluid enters the channel through the needle opening connected to the internal phase capillary at the upper end, while the sheath flow enters the needle opening connected to the external phase capillary at the lower end. The shear force between the core liquid and the sheath liquid dynamically concentrates the core liquid fluid in the center of the microchannel, and the shear force arranges the polymer chains along the final fiber flow direction. Here, solvent extraction is the process of phase inversion: the solution in the core liquid is replaced by the solution of the sheath liquid, and the solute is not dissolved in the sheath liquid. They will solidify into fibers downstream of the channel. During the whole process, the channel is placed vertically, and the produced fibers directly enter the water bath. The fibers are stable in the water bath and easy to handle and collect. The pumping parameters of the microfluidic syringe pump are 50μL / min for the internal phase liquid and 150μL / min for the external phase liquid.

[0062] The fiber diameter of the multifunctional suture produced in this case was 210.13±5.05μm, the pore diameter on the fiber was 0.87±0.29μm, and the maximum breaking force was 0.221±0.01 Newton. The analgesic duration lasted for 3 days, and the pain threshold on the 3rd day was 78.04±10.77% of the baseline value.

[0063] Example 4

[0064] (1) Preparation steps of microfluidic microchannel chip:

[0065] The microfluidic chip uses cylindrical glass capillaries with smaller and larger inner diameters (World Precision Instruments, Sarasota, USA) as the microchannels of the inner phase and outer phase, respectively. The inner phase capillary is coaxially nested in the outer phase capillary to obtain a microchannel chip kit. The diameter of the inner phase glass capillary is selected to be 100 μm, and the diameter of the outer phase glass capillary is selected to be 750 μm. The specific steps are: coaxially nest the core liquid glass capillary and the sheath liquid glass capillary and fix them on the slide with AB glue; align the center of the bottom of the needle plug and the entrance of the inner and outer phase glass capillaries respectively, and pay attention to the fit of the groove and the glass tube; finally, use a large amount of AB glue to seal the connection between the dispensing needle and the slide. Repeatedly wash with anhydrous ethanol and ultrapure water to obtain a microchannel chip.

[0066] (2) Preparation steps of inner phase liquid and outer phase liquid:

[0067] Prepare fiber precursor solution and continuous phase solution as inner phase solution and outer phase solution respectively. The inner phase solution solute is polycaprolactone (PCL, Mn=230,000) and ropivacaine, the inner phase solution solvent is N,N-dimethylformamide (DMF), the outer phase solution solute is polyethylene glycol, and the outer phase solution solvent is deionized water (ddH2O); the concentration of polycaprolactone in the inner phase solution is 10%, the concentration of ropivacaine is 10%, and the concentration of polyethylene glycol ester in the outer phase solution is 6% to 8%. The outer phase sheath solution is also used as a water bath for collecting solid fibers. Prepare the solution at room temperature.

[0068] (3) Preparation steps of multifunctional analgesic suture

[0069] The formulated fluid is introduced into the syringe pump of the microchannel, and the solute of the internal phase liquid is solidified in the glass capillary microchannel through the extraction of the external phase aqueous solution and the internal phase aqueous solvent to obtain a continuous solid fiber suture. Using a dual-drive syringe pump, the core liquid and the sheath liquid are introduced into the microchannel at the same time. The core fluid enters the channel through the needle opening connected to the internal phase capillary at the upper end, while the sheath flow enters the needle opening connected to the external phase capillary at the lower end. The shear force between the core liquid and the sheath liquid dynamically concentrates the core liquid fluid in the center of the microchannel, and the shear force arranges the polymer chains along the final fiber flow direction. Here, solvent extraction is the process of phase inversion: the solution in the core liquid is replaced by the solution of the sheath liquid, and the solute is not dissolved in the sheath liquid. They will solidify into fibers downstream of the channel. During the whole process, the channel is placed vertically, and the produced fibers directly enter the water bath. The fibers are stable in the water bath and easy to handle and collect. The pumping parameters of the microfluidic syringe pump are 50μL / min for the internal phase liquid and 200μL / min for the external phase liquid.

[0070] The fiber diameter of the multifunctional suture produced in this case was 196.56±7.68μm, the pore diameter on the fiber was 0.68±0.30μm, and the maximum breaking force was 0.184±0.01 Newton. The analgesic duration lasted for 3 days, and the pain threshold on the 3rd day was 55.54±6.45% of the baseline value.

[0071] Example 5

[0072] (1) Preparation steps of microfluidic microchannel chip:

[0073] The microfluidic chip uses cylindrical glass capillaries with smaller and larger inner diameters (World Precision Instruments, Sarasota, USA) as the microchannels of the inner phase and outer phase, respectively. The inner phase capillary is coaxially nested in the outer phase capillary to obtain a microchannel chip kit. The diameter of the inner phase glass capillary is selected to be 100 μm, and the diameter of the outer phase glass capillary is selected to be 750 μm. The specific steps are: coaxially nest the core liquid glass capillary and the sheath liquid glass capillary and fix them on the slide with AB glue; align the center of the bottom of the needle plug and the entrance of the inner and outer phase glass capillaries respectively, and pay attention to the fit of the groove and the glass tube; finally, use a large amount of AB glue to seal the connection between the dispensing needle and the slide. Repeatedly wash with anhydrous ethanol and ultrapure water to obtain a microchannel chip.

[0074] (2) Preparation steps of inner phase liquid and outer phase liquid:

[0075] Prepare fiber precursor solution and continuous phase solution as inner phase solution and outer phase solution respectively. The inner phase solution solute is polycaprolactone (PCL, Mn=230,000) and ropivacaine, the inner phase solution solvent is N,N-dimethylformamide (DMF), the outer phase solution solute is polyethylene glycol, and the outer phase solution solvent is deionized water (ddH2O); the concentration of polycaprolactone in the inner phase solution is 10%, the concentration of ropivacaine is 10%, and the concentration of polyethylene glycol ester in the outer phase solution is 6% to 8%. The outer phase sheath solution is also used as a water bath for collecting solid fibers. Prepare the solution at room temperature.

[0076] (3) Preparation steps of multifunctional analgesic suture

[0077] The formulated fluid is introduced into the syringe pump of the microchannel, and the solute of the internal phase liquid is solidified in the glass capillary microchannel through the extraction of the external phase aqueous solution and the internal phase aqueous solvent to obtain a continuous solid fiber suture. Using a dual-drive syringe pump, the core liquid and the sheath liquid are introduced into the microchannel at the same time. The core fluid enters the channel through the needle opening connected to the internal phase capillary at the upper end, while the sheath fluid enters the needle opening connected to the external phase capillary at the lower end. The shear force between the core liquid and the sheath liquid dynamically concentrates the core liquid fluid in the center of the microchannel, and the shear force arranges the polymer chains along the final fiber flow direction. Here, solvent extraction is the process of phase inversion: the solution in the core liquid is replaced by the solution of the sheath liquid, and the solute is not dissolved in the sheath liquid. They will solidify into fibers downstream of the channel. During the whole process, the channel is placed vertically, and the produced fibers directly enter the water bath. The fibers are stable in the water bath and easy to handle and collect. The pumping parameters of the microfluidic syringe pump are 50μL / min for the internal phase liquid and 500μL / min for the external phase liquid.

[0078] The fiber diameter of the multifunctional analgesic suture produced in this case was 163.40±6.39μm, the pore diameter on the fiber was 0.51±0.19μm, and the maximum breaking force was 0.108±0.005 Newton. The fiber had almost no analgesic effect, and the pain threshold on the third day was 30.98±6.94% of the baseline value. Figure 4 -B.

[0079] The present invention provides a multifunctional analgesic suture and its preparation method and application ideas and methods. There are many methods and ways to implement the technical solution. The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the protection scope of the present invention. All components not specified in this embodiment can be implemented by existing technologies.

Claims

1. A method for preparing a multifunctional analgesic suture, characterized in that: The steps include: (1) The inner phase capillary is coaxially nested in the outer phase capillary to construct a microchannel kit of the microfluidic chip; (2) preparing a fiber precursor solution containing polycaprolactone and analgesic drugs as the inner core liquid, and a continuous phase solution as the outer sheath liquid; (3) the inner phase core liquid and the outer phase sheath liquid prepared in step (2) are simultaneously and continuously injected into the microchannel set of the microfluidic chip in step (1), and the inner phase solution solute is solidified in the microchannel through the extraction effect of the outer phase sheath liquid on the inner phase core liquid solvent to obtain a continuous solid fiber; The solutes of the inner phase core liquid are polycaprolactone and analgesic drugs. In the inner phase core liquid, the mass concentration of polycaprolactone is 6% to 10%, and the mass concentration of the analgesic drugs is 5% to 10%; The analgesic drug is an aminoamide local anesthetic drug, including ropivacaine; the solvent of the inner phase core liquid is any one of N,N-dimethylformamide, dimethyl sulfoxide, and 2,2,2-trifluoroethanol; In step (2), the solute of the external phase sheath liquid is polyethylene glycol, and the solvent of the external phase sheath liquid is deionized water; the mass concentration of polyethylene glycol in the external phase sheath liquid is 6% to 8%; In step (3), the flow rates of the outer phase sheath liquid and the inner phase core liquid are controlled to be 100 μL / min:50 μL / min to 200 μL / min:50 μL / min.

2. The method for preparing the multifunctional analgesic suture according to claim 1, characterized in that: In step (1), the inner phase capillary is a glass capillary with a diameter of 100 μm to 300 μm; and the outer phase capillary is a glass capillary with a diameter of 580 μm to 750 μm.

3. The method for preparing the multifunctional analgesic suture according to claim 1, characterized in that: In step (3), the inner phase solution solute is solidified in the microchannel of the microfluidic chip at room temperature, and the outer phase sheath liquid is also used as a room temperature water bath liquid for collecting the solid fibers.

4. The multifunctional analgesic suture prepared by the preparation method according to any one of claims 1 to 3.

5. The multifunctional analgesic suture according to claim 4, characterized in that: The outer part of the suture is a biocompatible and degradable polymer material, and the inner part is wrapped with analgesic drugs.

6. Use of the multifunctional analgesic suture thread according to claim 4 in preparing products for suturing biological skin and deep tissues.

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