Drug-loaded nanofiber membrane / polylactic acid absorbable surgical suture and preparation method thereof

Abstract

This invention belongs to the field of suture technology, specifically relating to a drug-loaded suture and its preparation method. The drug-loaded suture provided by this invention includes a matrix and a drug loaded on the surface of the matrix; the matrix has a core-skin structure, the core layer of the matrix being polylactic acid filaments; the skin layer of the matrix is ​​a nanofiber membrane, the nanofiber membrane being composed of polycaprolactone and polyglycolic acid; the polyglycolic acid accounts for 10-90% of the mass percentage of the nanofiber membrane. The skin layer of the drug-loaded suture provided by this invention is prepared from two biodegradable materials with different degradation rates, polycaprolactone and polyglycolic acid. By limiting the ratio of polycaprolactone and polyglycolic acid in the skin layer, this invention can control the degradation cycle and drug release cycle of the drug-loaded suture, thereby adapting to different types of wounds with different healing times. Simultaneously, the core-skin structure of the drug-loaded suture provided by this invention provides excellent mechanical properties.

Description

Technical Field

[0001] This invention belongs to the field of suture technology, specifically relating to a drug-loaded suture and its preparation method. Background Technology

[0002] Polylactic acid (PLA) surgical sutures are widely used in the medical industry due to the abundant availability of raw materials, good biocompatibility and biodegradability, and their close similarity to the human body's pH. However, infection frequently occurs during the wound healing process after suturing. When infection occurs, the most common approach is to administer oral anti-inflammatory and analgesic drugs. However, because this involves systemic drug administration, it can cause significant side effects on tissues and organs other than the wound. Current solutions address this issue by drug-loaded sutures during manufacturing. Existing drug loading methods include the following:

[0003] 1. Direct impregnation method for drug delivery:

[0004] This method involves immersing the polylactic acid sutures directly in the medication solution before surgery. While this achieves drug delivery, the total drug release time of the sutures is only a few hours, which is too short to achieve the goal of continuous drug release.

[0005] 2. Drug delivery mode using microcapsules:

[0006] Drugs and other carrier materials are prepared into microspheres, which are then loaded onto sutures through other processing methods to obtain drug-loaded microsphere sutures. Although this drug loading method achieves the purpose of drug loading, the drug loading is not strong enough. When the suture is subjected to friction, the microspheres will detach, thereby reducing the drug loading capacity.

[0007] 3. Surface coating method for drug delivery:

[0008] After preparing the drug-loaded finishing solution, the suture is directly coated to achieve the effect of drug loading. This drug loading method simply involves mixing the drug with the polymer and then applying it to the suture surface, making it difficult to control the amount of drug loaded and the drug dispersion effect.

[0009] Existing drug-loaded polylactic acid (PLA) surgical sutures have exhibited adverse effects such as excessively rapid drug release and difficulty in controlling drug loading. The drug release rate of drug-loaded PLA sutures must be appropriate in terms of speed and cycle. Release that is too fast or too slow will affect the wound healing process. Therefore, the drug release rate of the suture needs to be controlled during the manufacturing process to match the healing time of the sutured wound.

[0010] To slow down drug release rates, researchers investigated drug-loaded spinning methods: drugs are electrospun into the fibers to achieve drug loading. This method allows for slow drug release as the fibers degrade, but the release cycle is unpredictable, and this method also affects the mechanical properties of drug-loaded polylactic acid fibers.

[0011] The preparation of drug-loaded polylactic acid sutures with both good mechanical properties and good drug release behavior is a technical problem that urgently needs to be solved. Summary of the Invention

[0012] In view of this, the present invention provides a drug-loaded suture and its preparation method. The drug-loaded suture provided by the present invention has a degradation rate that can adapt to wounds of different types and at different times, while also having good mechanical properties.

[0013] To address the aforementioned technical problems, the present invention provides a drug-loaded suture, comprising a matrix and a drug loaded on the surface of the matrix; the matrix has a core-skin structure, the core layer of the matrix being polylactic acid filaments; the skin layer of the matrix being a nanofiber membrane, the nanofiber membrane being composed of polycaprolactone and polyglycolic acid; the polyglycolic acid accounts for 10-90% of the mass percentage of the nanofiber membrane.

[0014] Preferably, the polyglycolic acid comprises 20-80% of the nanofiber membrane by mass.

[0015] Preferably, the mass ratio of the core layer to the skin layer is 6-8:2-4.

[0016] Preferably, the drug is an antibacterial and anti-inflammatory drug;

[0017] The mass ratio of the drug to the nanofiber membrane is 1 to 3:100.

[0018] The present invention also provides a method for preparing the drug-loaded suture described in the above technical solution, comprising the following steps:

[0019] Polycaprolactone and polyglycolic acid were dissolved in a mixed solution of dichloromethane and N,N-dimethylformamide to obtain a matrix solution;

[0020] The matrix solution and the drug are mixed to obtain a spinning solution;

[0021] The drug-loaded suture is obtained by spinning polylactic acid filament as the core yarn using the spinning solution.

[0022] Preferably, the total mass percentage of polycaprolactone and polyglycolic acid in the matrix solution is 10-20%.

[0023] Preferably, the mass ratio of dichloromethane to N,N-dimethylformamide in the mixed solution of dichloromethane and N,N-dimethylformamide is 1:0.25 to 6.

[0024] Preferably, the dissolution is carried out under stirring conditions, the stirring speed is 500-800 r / min, and the stirring time is 12-24 h.

[0025] Preferably, the mixing is carried out under stirring conditions, the stirring speed is 500-800 r / min, and the stirring time is 8-20 h.

[0026] Preferably, the spinning is electrospinning, and the voltage of the electrospinning is 12.5 to 20.5 kV.

[0027] This invention provides a drug-loaded suture, comprising a matrix and a drug loaded on the surface of the matrix; the matrix has a core-skin structure, the core layer of the matrix being polylactic acid filaments; the skin layer of the matrix is ​​a nanofiber membrane, the nanofiber membrane being composed of polycaprolactone and polyglycolic acid; the polyglycolic acid accounts for 10-90% of the mass percentage of the nanofiber membrane. The skin layer of the drug-loaded suture provided by this invention is prepared from two biodegradable materials with different degradation rates, polycaprolactone and polyglycolic acid. By limiting the ratio of polycaprolactone and polyglycolic acid in the skin layer, this invention can control the degradation and drug release cycles of the drug-loaded suture, thereby adapting to different types of wounds with different healing times. Simultaneously, the core-skin structure of the drug-loaded suture provided by this invention provides excellent mechanical properties. The drug-loaded suture provided by this invention uses polylactic acid as the core yarn and coats the drug-loaded nanofiber membrane with strong extensibility and elasticity, providing excellent mechanical properties for the suture. Attached Figure Description

[0028] Figure 1 This is a schematic diagram of the electrospinning process in the embodiment;

[0029] Figure 2 SEM images of the side surfaces of the drug-loaded sutures prepared in Examples 1-6;

[0030] Figure 3 SEM images of the cross-sections of the drug-loaded sutures prepared in Examples 2-6 and the polylactic acid filaments used in the examples;

[0031] Figure 4 The mechanical properties of the drug-loaded sutures prepared in Examples 1-9 are shown in the dot-line diagrams, where (a) is a dot-line diagram comparing the breaking strength and (b) is a dot-line diagram comparing the breaking elongation.

[0032] Figure 5SEM images of the drug-loaded sutures prepared in Examples 1, 3-5 and 8 after degradation at different times;

[0033] Figure 6 The graph shows the mass loss of the drug-loaded sutures in Examples 1-5 and 8 after different degradation times.

[0034] Figure 7 The graph shows the linear relationship of degradation fitting of the drug-loaded sutures prepared in Examples 1, 3-6 and 8;

[0035] Figure 8 The cumulative drug release curves of the drug-loaded sutures prepared in Examples 2-5 at different times are shown.

[0036] Figure 9 SEM images of the sides of the sutures prepared in Examples 10-14 and Comparative Example 1;

[0037] Figure 10 The following are comparative dot-line diagrams of the mechanical properties of the sutures prepared in Examples 10-14, where (a) is a comparative dot-line diagram of breaking strength and (b) is a comparative dot-line diagram of breaking elongation.

[0038] Figure 11 The images show the antibacterial properties of the sutures prepared in Examples 10, 12, 14 and Comparative Example 1. The top row shows the antibacterial properties against Escherichia coli, and the bottom row shows the antibacterial properties against Staphylococcus aureus.

[0039] Figure 12 SEM images of the drug-loaded sutures prepared in Examples 10, 12, 14 and Comparative Example 1 after degradation over different time periods;

[0040] Figure 13 The diagram shows the mass loss of the drug-loaded sutures prepared in Examples 10-14 and Comparative Example 1 after degradation over different time periods.

[0041] Figure 14 The graph shows the linear relationship between the degradation of the sutures prepared in Examples 10-14 and Comparative Example 1.

[0042] Figure 15 The cumulative drug release curves of the drug-loaded sutures prepared in Examples 10, 12 and 14 at different times are shown. Detailed Implementation

[0043] This invention provides a drug-loaded suture, comprising a matrix and a drug loaded on the surface of the matrix; the matrix has a core-skin structure, the core layer of the matrix being polylactic acid filaments; the skin layer of the matrix being a nanofiber membrane, the nanofiber membrane being composed of polycaprolactone and polyglycolic acid; the polyglycolic acid accounts for 10-90% of the mass percentage of the nanofiber membrane, preferably 20-80%.

[0044] In this invention, the mass ratio of the core layer to the skin layer is preferably 6-8:2-4, and more preferably 7:3.

[0045] In this invention, the drug is preferably an antibacterial and anti-inflammatory drug; the antibacterial and anti-inflammatory drug is preferably ciprofloxacin. In this invention, the mass ratio of the drug to the nanofiber membrane is preferably 1-3:100, more preferably 1.5-2.5:100.

[0046] In this invention, polycaprolactone (PCL) and polyglycolic acid (PGA) are biodegradable materials and harmless to the human body; and polyglycolic acid (C4H4O4) n ) and polycaprolactone ((C6H 10 O2) n The degradation rates of poly(lactic acid) vary. This invention uses nanofiber membranes prepared with different ratios of polycaprolactone and polyglycolic acid as the outer layer, allowing for control over the degradation rate, i.e., controllable degradation. In this invention, polylactic acid (C3H4O2) is used... n It possesses excellent biological properties. In this invention, the polylactic acid exhibits excellent biocompatibility and biodegradability, and has the advantage of being close to the acid-base balance of the human body.

[0047] The present invention also provides a method for preparing the drug-loaded suture described in the above technical solution, comprising the following steps:

[0048] Polycaprolactone and polyglycolic acid were dissolved in a mixed solution of dichloromethane and N,N-dimethylformamide to obtain a matrix solution;

[0049] The matrix solution and the drug are mixed to obtain a spinning solution;

[0050] The drug-loaded suture is obtained by spinning polylactic acid filament as the core yarn using the spinning solution.

[0051] This invention involves dissolving polycaprolactone and polyglycolic acid in a mixed solution of dichloromethane and N,N-dimethylformamide to obtain a matrix solution. In this invention, the mass ratio of dichloromethane to N,N-dimethylformamide in the mixed solution is preferably 1:0.25–6, more preferably 1:0.25–2.3. In this invention, the mixed solution of dichloromethane and N,N-dimethylformamide serves as a solvent that readily dissolves polycaprolactone and polyglycolic acid.

[0052] In this invention, the percentage content of polycaprolactone and polyglycolic acid in the total mass of the matrix solution is preferably 10-20%, more preferably 12-18%.

[0053] In this invention, the dissolution is preferably carried out under stirring conditions, the stirring speed is preferably 500-800 r / min, more preferably 600-700 r / min; the stirring time is preferably 12-24 h, more preferably 15-20 h.

[0054] After obtaining the matrix solution, the present invention mixes the matrix solution with the drug to obtain a spinning solution. In the present invention, the mixing is preferably carried out under stirring conditions, the stirring speed is preferably 500-800 r / min, more preferably 300-700 r / min; the stirring time is preferably 8-20 h, more preferably 10-15 h.

[0055] After obtaining the spinning solution, the present invention uses polylactic acid filament as the core yarn and spins it using the spinning solution to obtain the drug-loaded suture. In the present invention, the fineness of the polylactic acid filament is preferably 95-105 dtex, more preferably 100 dtex. In the present invention, the number of individual polylactic acid filaments is preferably 50. The present invention preferably twists the polylactic acid filament before spinning; the twisting method is preferably Z-twist, and the twisting coefficient is preferably 100. In the present invention, after twisting, the process preferably includes: heat setting, sterilization, and drying the twisted product sequentially. In the present invention, the heat setting temperature is preferably 55-65℃, more preferably 60℃; the heat setting time is preferably 25-35 min, more preferably 30 min. In the present invention, the heat setting is preferably carried out in a vacuum oven. In the present invention, the sterilization is preferably by immersing the heat-set product in medical alcohol; the immersion time is preferably 9-11 min, more preferably 10 min. In this invention, the drying temperature is preferably 35-45°C, more preferably 40°C; the drying time is preferably 55-65 min, more preferably 60 min.

[0056] In this invention, the spinning is preferably electrospinning. In this invention, Figure 1This is a schematic diagram of the electrospinning process. Specifically, positive and negative electrodes are drawn from the generating device of a DC high-voltage generator and connected to two syringes (containing spinning solution). The distance between the two needles of the two syringes, the distance between the two needles and the bell mouth, and the distance from the bell mouth to the winding roller are adjusted. The polylactic acid core yarn is drawn out and wound onto the winding roller to achieve continuous winding. In this invention, the injection speed of the spinning solution is preferably 0.01-0.08 mL / min, more preferably 0.02-0.07 mL / min; the rotation speed of the annular collector for electrospinning is preferably 300-600 r / min, more preferably 350-550 r / min; the winding speed of electrospinning is preferably 1-6 cm / min, more preferably 2-5 cm / min. In this invention, the voltage for electrospinning is preferably 12.5-20.5 kV, more preferably 15-20 kV.

[0057] In this invention, the process after spinning preferably further includes drying the spun product. In this invention, the drying temperature is preferably 40–50°C, more preferably 40–45°C; the drying time is preferably 3–5 hours, more preferably 3–4 hours.

[0058] To further illustrate the present invention, the technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0059] The embodiments of the present invention do not limit the amount or weight of the raw materials used; the drug-loaded sutures can be prepared according to the mass ratio.

[0060] The sources of the raw materials used in the examples are shown in Table 1.

[0061] Table 1 shows the sources of the raw materials used in the examples.

[0062]

[0063]

[0064] Example 1

[0065] Polyglycolic acid (PGA) and polycaprolactone (PCL) were dissolved in a mixed solution of dichloromethane and N,N-dimethylformamide in a mass ratio of 7:3 at a mass ratio of 80:20 (stirred for 20 h at a speed of 650 r / min) to obtain a matrix solution with a total mass concentration of 12% of polycaprolactone and polyglycolic acid.

[0066] The matrix solution and ciprofloxacin (the total mass of polycaprolactone and polyglycolic acid and the mass ratio of ciprofloxacin were 100:2) were stirred and mixed at a speed of 650 r / min for 15 h to obtain the spinning solution.

[0067] Polylactic acid filaments with a fineness of 100 dtex and 50 monofilaments were used as core yarns. The polylactic acid filaments were twisted, with Z-twist and a twist coefficient of 100. The twisted polylactic acid filaments were heat-set in a vacuum oven at 60°C for 30 minutes, then immersed in medical alcohol for 10 minutes for sterilization. The sterilized product was then placed in a forced-air drying oven and dried at 40°C for 60 minutes.

[0068] The spinning solution was placed in two syringes, and the positive and negative terminals of the DC high voltage generator were drawn out and connected to the two syringes respectively. The distance between the two needles, the distance between the two needles and the bell mouth, and the distance between the bell mouth and the winding roller were adjusted. The polylactic acid core yarn was drawn out and wound onto the winding roller for electrospinning. The electrospinning conditions were as follows: injection speed of 0.08 mL / min, ring collector rotation speed of 300 r / min, winding speed of 6 cm / min, and voltage of ±12.5 kV. The spun product was dried at 40℃ for 3 h to obtain the drug-loaded suture.

[0069] Example 2

[0070] The drug-loaded suture was prepared according to the method of Example 1, except that the mass ratio of polyglycolic acid to polycaprolactone (PGA / PCL) was 70:30.

[0071] Example 3

[0072] The drug-loaded suture was prepared according to the method of Example 1, except that the mass ratio of polyglycolic acid to polycaprolactone was 60:40.

[0073] Example 4

[0074] The drug-loaded suture was prepared according to the method of Example 1, except that the mass ratio of polyglycolic acid to polycaprolactone was 50:50.

[0075] Example 5

[0076] The drug-loaded suture was prepared according to the method of Example 1, except that the mass ratio of polyglycolic acid to polycaprolactone was 40:60.

[0077] Example 6

[0078] The drug-loaded suture was prepared according to the method of Example 1, except that the mass ratio of polyglycolic acid to polycaprolactone was 30:70.

[0079] Example 7

[0080] The drug-loaded suture was prepared according to the method of Example 1, except that the mass ratio of polyglycolic acid to polycaprolactone was 90:10.

[0081] Example 8

[0082] The drug-loaded suture was prepared according to the method of Example 1, except that the mass ratio of polyglycolic acid to polycaprolactone was 20:80.

[0083] Example 9

[0084] The drug-loaded suture was prepared according to the method of Example 1, except that the mass ratio of polyglycolic acid to polycaprolactone was 10:90.

[0085] The lateral surfaces of the drug-loaded sutures prepared in Examples 1-6 were examined using scanning electron microscopy (SEM), and SEM images were obtained, as shown below. Figure 2 As shown. By Figure 2 It can be seen that with the continuous increase of polyglycolic acid (PEG) content, the disorder of the drug-loaded suture surface decreases, the fiber orientation gradually increases, the fiber bundles on the surface become more regular, and the surface beads also gradually decrease with the increase of PEG content. This is because high molecular weight PEG is easier to draw into fibers and has better directionality, thus improving the suture surface morphology with increasing PEG content. This has a certain influence on the mechanical properties of the suture due to the different carrier ratios. In addition, the presence of the core yarn improves the collection effect when collecting the fiber membrane of the sheath, resulting in higher quality yarn with more uniform diameter.

[0086] The cross-sections of the drug-loaded sutures prepared in Examples 2-6 and the polylactic acid filaments used in the examples were examined using scanning electron microscopy (SEM), and SEM images were obtained, as shown below. Figure 3 As shown. By Figure 3 It can be seen that the skin layer coating effect of each carrier ratio is good, and they can all be uniformly wrapped on the core yarn, indicating that a core-coated suture with a skin-core structure can be successfully prepared under the experimental conditions. With the increase of polyglycolic acid content, the thickness of the skin layer gradually increases, and the yarn diameter gradually increases. This is because polyglycolic acid forms fibers at a faster rate during spinning. Therefore, under the same collection and winding rates, the spinning solution with a higher polyglycolic acid content has a thicker fiber coating on the core yarn, resulting in a larger diameter drug-loaded suture. This phenomenon also affects the mechanical properties of the suture.

[0087] The mechanical properties of the drug-loaded sutures prepared in Examples 1-9 were tested using an electronic single yarn tensile tester. The data of elongation at break and tensile strength at break were recorded on the electronic display screen. The tests were performed three times, and the average value was taken. The results are listed in Table 2.

[0088] Table 2 Mechanical properties of drug-loaded sutures prepared in Examples 1-9

[0089] Example Fracture strength (cN / tex) Elongation at break (%) Example 1 22.92 30.27 Example 2 22.535 27.18 Example 3 21.47 26.99 Example 4 20.5 25.63 Example 5 20.41 26.64 Example 6 22.68 27.56 Example 7 23.05 30.41 Example 8 22.78 27.57 Example 9 23.36 30.93

[0090] Based on the data in Table 2, a line graph comparing the mechanical properties of the drug-loaded sutures prepared in Examples 1-9 was plotted, as shown. Figure 4 As shown, (a) is a line graph comparing fracture strength, and (b) is a line graph comparing fracture elongation. Figure 4 It is evident that the ratio of polycaprolactone (PCL) to polyglycolic acid (PGA) has a significant impact on the mechanical properties of the suture. When the ratio of PGA to PCL is 40:60 (PCL content in the dermis is 40% by mass), the suture's tensile strength reaches its lowest value. When the ratio is 50:50 (PCL content in the dermis is 50% by mass), the suture's elongation at break reaches its lowest value. When the ratio is less than 40:60 (PCL content in the dermis is less than 40% by mass), the suture shows a trend of gradually decreasing tensile strength and elongation at break as the amount of PGA increases. Conversely, when the ratio is greater than 50:50 (PCL content in the dermis is greater than 50% by mass), the suture shows a trend of gradually increasing tensile strength and elongation at break as the amount of PGA increases. This phenomenon indicates that increasing the amount of poly(lactic acid) lactone (PEL) is beneficial to improving the mechanical properties of the suture. However, due to the poor spinning effect during the preparation process of sutures with a low PEL content, their mechanical properties are somewhat affected. When the PEL content reaches 40%, the spinning and coating effect gradually improves, thus enhancing the mechanical properties. Furthermore, comparing the mechanical properties of pure polylactic acid (PLA) fibers, it can be seen that the mechanical properties of core-spun yarn sutures are stronger than those of PLA filament core yarns, indicating that the core-spun yarn structure is beneficial to improving the mechanical properties of the suture.

[0091] Verify the effect of different ratios of polycaprolactone and polyglycolic acid on degradation performance:

[0092] Construction of the in vitro degradation system: To better simulate the environment within the human body, a phosphate buffer solution was selected as the degradation solution, mainly containing Na₂HPO₄, KH₂PO₄, NaCl, and KCl at concentrations of 1.56 g / L, 0.20 g / L, 8.00 g / L, and 0.20 g / L, respectively. After preparing the degradation solution, a certain mass of coreless sutures with different carrier ratios and drug loadings were weighed, vacuum dried, labeled, and placed in centrifuge bottles containing 30 mL of degradation solution. Each centrifuge bottle was then placed in a water bath at 37°C and 100 rpm. Samples were taken every week, washed three times with deionized water, and then dried in a vacuum oven at 45°C to constant weight before performance testing and characterization.

[0093] 1) Changes in surface morphology during degradation:

[0094] The drug-loaded sutures prepared in Examples 1, 3-5, and 8 were degraded in the above-described in vitro degradation system. Scanning electron microscopy (SEM) images of the products after 2, 6, and 10 weeks of degradation were obtained, as shown below. Figure 5 As shown. By Figure 5 It can be seen that the surface morphology of cored yarn sutures with different ratios of polycaprolactone and polyglycolic acid (PGA) all exhibited a certain degree of degradation with prolonged degradation time: the fiber bundles on the surface gradually became disordered, the fiber diameter became thinner, and some fiber surfaces developed voids or even broke. When degradation reached 10 weeks, the diameter of the surface fibers in both PGA and PGA cored yarn sutures with different ratios showed a significant decrease, and most fiber surfaces became blurred, developed voids, and even experienced significant breakage. Furthermore, with the continuous increase of PGA content, the degree of surface morphology degradation of the sutures continuously increased, indicating that the degradation rate of fibers in sutures with different carrier ratios continuously increased with the increase of PGA content. This is because PGA has a faster degradation rate, and its increased proportion leads to a continuously increasing fiber degradation rate, thus accelerating the degradation rate of the sutures and shortening the degradation cycle.

[0095] 2) Mass loss during degradation:

[0096] After the sutures had degraded for a certain period of time, they were removed and repeatedly washed with deionized water. After washing, they were placed in a vacuum oven to dry, and then the mass of the dried sutures was measured using a precision electronic balance and the data was recorded. The results are listed in Table 3.

[0097] Table 3. Mass loss of drug-loaded sutures in Examples 1, 3-6 and 8 after different degradation times.

[0098]

[0099] Based on Table 3, plot the mass loss of the drug-loaded sutures in Examples 1-5 and 8 after different degradation times using dot plots. Figure 6 As shown. (Combined with Table 3 and...) Figure 6 Comprehensive analysis shows that cored yarn sutures with different polycaprolactone and polyglycolic acid ratios all underwent a certain degree of degradation with the extension of degradation time, and the quality of the sutures decreased continuously with the increase of degradation time. With the increase of polyglycolic acid content, the quality loss rate of the sutures continuously increased, indicating that the sutures with higher polyglycolic acid content had a more obvious degradation effect, that is, a faster degradation rate and greater quality loss.

[0100] To further investigate the degradation patterns of cored yarn sutures with different polycaprolactone and polyglycolic acid ratios, linear fitting was performed based on existing data. The curve of the suture mass (represented by y) changing with degradation time (represented by x) during the degradation process was fitted, and the corresponding fitting equation was obtained. The time for complete degradation of cored yarn sutures with different carrier ratios was then inferred from the equation. The results are listed in Table 4. Figure 7 The graph shows the linear relationship of degradation fitting of the drug-loaded sutures prepared in Examples 1, 3-6 and 8.

[0101] Table 4. Degradation fitting equations for the drug-loaded sutures prepared in Examples 1, 3-6 and 8.

[0102] Example (PGA / PCL) Fitting equation <![CDATA[R 2 ]]> Complete degradation time / week Example 8 (20 / 80) y = -1.1287x + 150.3014 0.9808 133.16 Example 6 (30 / 70) y = -1.4824x + 159.1144 0.9736 107.34 Example 5 (40 / 60) y = -1.7527x + 152.6118 0.9889 87.07 Example 4 (50 / 50) y = -2.1056x + 156.5369 0.9866 74.34 Example 3 (60 / 40) y = -2.3484x + 155.8989 0.9833 66.39 Example 1 (80 / 20) y = -2.5107x + 158.2204 0.9545 63.02

[0103] Combine Table 4 and Figure 7 It can be seen that the drug-loaded suture provided by the present invention can control the degradation time by limiting different ratios of polycaprolactone and polyglycolic acid.

[0104] Effect of different polycaprolactone and polyglycolic acid ratios on drug release performance:

[0105] Weigh 0.20g of KCl solid, 0.20g of KH2PO4 solid, 1.56g of Na2HPO4 solid, and 8.00g of NaCl solid using an electronic balance. Dissolve the solids and transfer them to a 1000mL volumetric flask. Make up to the mark and adjust the pH to 7.2–7.4 to obtain PBS buffer solution to simulate the internal environment of the human body.

[0106] The maximum absorption wavelength of ciprofloxacin was determined to be 271 nm by measuring the UV-Vis absorption of the ciprofloxacin solution. Then, a standard curve for ciprofloxacin was obtained by fitting the curve to Origin, yielding the linear equation y = 0.019x + 98.2, R0. 2 ≈0.982, where y is absorbance and x is concentration. R 2The value is close to 1, indicating a good linear relationship between absorbance y and concentration x. After obtaining the standard curve, 0.1 g samples of coreless yarn sutures with different carrier ratios and drug loadings were weighed. After drying, the samples were placed in centrifuge bottles containing 50 mL of PBS buffer, and then placed in a water bath at 100 r / min and 37 °C. At 5 h, 10 h, 15 h, 20 h, 25 h, 30 h, 35 h, 45 h, 55 h, and 65 h after sample addition, 3 mL of solution was taken from the conical flask, and 3 mL of PBS buffer was added simultaneously to ensure that the original sustained-release system was not disrupted. The absorbance of the 3 mL solution was measured using a UV spectrophotometer at a wavelength of 271 nm. The concentration of ciprofloxacin in the 3 mL solution was calculated using PBS buffer as a reference. This yielded the ciprofloxacin content in the solution at different times. The cumulative drug release was then calculated, and a cumulative drug release curve was plotted. The drug release rate at different times was calculated, and the results are listed in Table 5.

[0107] Table 5. Drug release rates of the drug-loaded sutures prepared in Examples 3-6 at different times.

[0108]

[0109] Based on Table 5, plot the cumulative drug release curves of the drug-loaded sutures prepared in Examples 3-6 at different times, as shown below. Figure 8 As shown.

[0110] Combined with Table 5 and Figure 8 It can be seen that the ratio of polycaprolactone to polyglycolic acid (PEG) has a significant impact on the drug release rate of the drug-loaded suture. The slope of the drug release curve for sutures with a PEG content exceeding 50% is larger in each time period than that for sutures with a PEG content below 50%, indicating that the drug release is faster with a higher PEG content. This is because sutures with a higher PEG content degrade faster, meaning more drug is released from the nanofiber membrane, resulting in higher cumulative drug release. Furthermore, the curve slope is very steep in the first 10 hours of degradation, indicating a rapid drug release rate. Within 10 hours, the cumulative drug release rate of sutures with various carrier ratios all reached over 20%.

[0111] Example 10

[0112] The drug-loaded suture was prepared according to the method of Example 2, except that the total mass ratio of polycaprolactone and polyglycolic acid to ciprofloxacin was 100:1.

[0113] Example 11

[0114] The drug-loaded suture was prepared according to the method of Example 10, except that the total mass ratio of polycaprolactone and polyglycolic acid to ciprofloxacin was 100:1.5.

[0115] Example 12

[0116] The drug-loaded suture was prepared according to the method of Example 10, except that the total mass ratio of polycaprolactone and polyglycolic acid to ciprofloxacin was 100:2.

[0117] Example 13

[0118] The drug-loaded suture was prepared according to the method of Example 10, except that the total mass ratio of polycaprolactone and polyglycolic acid to ciprofloxacin was 100:2.5.

[0119] Example 14

[0120] The drug-loaded suture was prepared according to the method of Example 10, except that the total mass ratio of polycaprolactone and polyglycolic acid to ciprofloxacin was 100:3.

[0121] Comparative Example 1

[0122] The drug-loaded suture was prepared according to the method of Example 10, except that ciprofloxacin was not added and the matrix solution was used directly as the spinning solution.

[0123] Effect of different drug loading on drug-loaded sutures

[0124] 1) Effect of different drug loading on the surface morphology of drug-loaded sutures

[0125] The lateral surfaces of the sutures prepared in Examples 10-14 and Comparative Example 1 were observed using a scanning electron microscope (SEM), and SEM images (×100) were obtained. Figure 9 As shown. By Figure 9 It is known that as the drug loading increases, the morphology of the suture surface gradually deteriorates. The fiber bundles exhibit some orientation, but the overall surface morphology is relatively chaotic, and the diameter of the suture increases. This phenomenon is mainly due to two reasons. Firstly, the addition of the drug affects the fiber-forming state during electrospinning, leading to a greater impact on fiber collection and poorer winding effect when the fibers are wound into yarn, resulting in a more chaotic surface morphology. The higher the drug content, the more chaotic the fiber morphology on the suture surface. Secondly, after the drug is added to the electrospinning solution, the viscosity increases. At the same injection speed, under high-voltage electrospinning, the higher the drug content of the spinning solution, the more fibers are drawn into fibers. Therefore, the collector collects more fibers in the same amount of time, resulting in a thicker yarn and a larger suture diameter.

[0126] 2) Effect of different drug loading on the mechanical properties of sutures

[0127] The mechanical properties of the drug-loaded sutures prepared in Examples 10-14 were tested using an electronic single yarn tensile tester. The data of elongation at break and tensile strength at break were recorded on the electronic display screen. The tests were performed three times and the average value was taken. The results are listed in Table 6.

[0128] Table 6 Mechanical properties of the drug-loaded sutures prepared in Examples 10-14

[0129] Example (Drug Loading) Fracture strength (cN / tex) Elongation at break (%) Example 10 (1%) 23.26 30.27 Example 11 (1.5%) 23.54 30.63 Example 12 (2%) 23.07 30.04 Example 13 (2.5%) 22.62 29.78 Example 14 (3%) 21.97 29.02 Comparative Example 1(0) 21.88 29.62

[0130] Based on the data in Table 6, a dotted line graph comparing the mechanical properties of the sutures prepared in Examples 10-14 was plotted, as shown. Figure 10 As shown, (a) is a line graph comparing fracture strength, and (b) is a line graph comparing fracture elongation. Figure 10 It is evident that the amount of drug loading has a significant impact on the mechanical properties of drug-loaded sutures. The breaking strength and elongation at break of cored yarn sutures with different drug loadings initially increase and then decrease with increasing drug content. When the drug content exceeds 1.5%, the mechanical properties of the cortex decrease sharply. This is partly due to the fact that the addition of a large amount of drug disrupts the original structure of the polymer material, greatly reducing the intermolecular interaction forces and resulting in poor fiber condition and loose structure on the suture surface. On the other hand, when a large amount of drug is added, the drug dispersion is relatively poor, which also greatly affects the spinning effect during the electrospinning process, resulting in poor suture surface quality and thus affecting its mechanical properties.

[0131] Effects of different drug loading on the antibacterial properties of sutures

[0132] Preparation of culture medium: Weigh 2.5g beef extract, 5g peptone and 2.5g sodium hydroxide into a 1L beaker, add 500mL deionized water and stir quickly with a glass rod until it becomes a bright yellow transparent solution. Adjust the pH of the culture medium to between 7.5 with sodium hydroxide solution, and sterilize in an autoclave at 512-15℃ for 305 minutes.

[0133] Preparation of PBS buffer: Weigh 1.36g of potassium dihydrogen phosphate (KH2PO4) and 2.84g of sodium dihydrogen phosphate (Na2HPO4) and dissolve them in 1000mL of deionized water. Adjust the pH to 7.4 with sodium hydroxide solution and sterilize at high temperature for 30min before use.

[0134] Bacterial culture: Gram-negative bacteria Escherichia coli (E. coli) and Gram-positive bacteria Staphylococcus aureus (S. aureus) were selected. 250 mL of culture medium was placed in an Erlenmeyer flask and the bacteria were incubated in liquid culture medium at 37°C for 24 h for later use.

[0135] Inhibition band method: First, prepare sterile culture medium. Pour 25 mL of agar medium into a sterile Petri dish and allow it to solidify. Pour 200 μL of cultured bacteria into each Petri dish of prepared sterile medium and allow it to solidify. The inoculated agar dishes should be used within 1 hour. Using sterile forceps, place the sample and control sample in the center of the Petri dish respectively, pressing them evenly onto the agar medium until there is good contact between the sample and the agar medium. After placing the sample on the agar medium, immediately place it in an incubator at 37°C for 18-24 hours, ensuring that the sample and agar medium remain in contact throughout the incubation period.

[0136] Calculation and evaluation of results: At least 3 measurements were taken for each sample, and the width of the antibacterial band of the sample was calculated according to formula (1).

[0137] H=(Dd) / 2 (1)

[0138] In formula (1):

[0139] H represents the width of the antibacterial band, measured in millimeters (mm).

[0140] D is the average outer diameter of the antibacterial zone, in millimeters (mm);

[0141] D is the diameter of the sample, in millimeters (mm).

[0142] After determining the inhibition zone, the antibacterial effect of each sample was evaluated according to Table 3.3 based on the presence or absence of bacterial growth and the width of the inhibition zone. (Refer to standard GB / T 20944.1—2007)

[0143] Table 3.3 Evaluation Criteria for Antibacterial Effect

[0144]

[0145]

[0146] When all samples meet the "good effect" requirement in the table, the sample is considered to have antibacterial effect.

[0147] The antibacterial properties of sutures with different drug loadings were tested using the antibacterial band method. *Escherichia coli* and *Staphylococcus aureus* were selected as target bacteria, and sutures with 0% drug loading were selected as a blank control. The test results are as follows: Figure 11 As shown, the top row contains images of the antibacterial properties against *Escherichia coli*, and the bottom row contains images of the antibacterial properties against *Staphylococcus aureus*. Figure 11 It can be seen that the antibacterial properties of drug-loaded cored yarn sutures are far superior to those of unloaded yarns. The antibacterial bands in both cases meet the conditions for good efficacy, and the antibacterial bands of the sutures become wider as the amount of drug loaded increases.

[0148] Effect of different drug loading on suture degradation properties:

[0149] The degradation performance was tested according to the method described above for verifying the effect of different ratios of polycaprolactone and polyglycolic acid on degradation performance.

[0150] 1) Changes in surface morphology during degradation

[0151] The drug-loaded sutures prepared in Examples 10-14 and Comparative Example 1 were subjected to the above-described in vitro degradation system. Scanning electron microscopy (SEM) images were obtained after 2, 6, and 10 weeks of degradation. Figure 12 As shown. By Figure 12 It can be seen that the surface morphology of cored yarn sutures with different drug loadings undergoes a certain degree of degradation with prolonged degradation time: the fiber bundles on the surface gradually become disordered, the fiber diameter becomes thinner, and some fiber surfaces develop voids or even break. During the fiber degradation process, more water molecules enter the fibers of the cored yarn, resulting in greater water absorption. This is due to the presence of the core-sheath structure, which creates more gaps between the fibers, making it easier for water molecules to enter the suture and thus accelerating degradation and increasing the degradation rate.

[0152] 2) Mass loss during degradation:

[0153] After the sutures degraded for a certain period of time, they were removed and repeatedly washed with deionized water. After washing, they were placed in a vacuum oven to dry, and then the mass of the dried sutures was measured and the data was recorded using a precision electronic balance. The results are listed in Table 7.

[0154] Table 7. Mass loss of drug-loaded sutures from Examples 10-14 after different degradation times.

[0155]

[0156]

[0157] Based on Table 7, plot the mass loss of the drug-loaded sutures in Examples 10-14 and Comparative Example 1 after different degradation times as shown in the dot plot. Figure 13 As shown. (Combined with Table 7 and...) Figure 13 Comprehensive analysis shows that, during the degradation process, all cored yarn sutures with different drug loadings underwent degradation over time. Compared with unmedicated sutures, drug-loaded sutures showed a relatively lower mass loss rate over time. The amount of drug loading was not linearly related to the degradation rate of the suture, but the addition of drug slowed down the degradation process.

[0158] To further investigate the degradation patterns of cored yarn sutures with different drug loadings, linear fitting was performed based on existing data. The curve of the suture mass (represented by y) changing with degradation time (represented by x) during the degradation process was fitted, and the corresponding fitting equation was obtained. The time for complete degradation of cored yarn sutures with different drug loadings was then inferred from the equation. The results are listed in Table 8. Figure 14 The graph shows the linear relationship between the degradation of the sutures prepared in Examples 10-14 and Comparative Example 1.

[0159] Table 8. Degradation fitting equations of the drug-loaded sutures prepared in Examples 10-14 and Comparative Example 1.

[0160] Example (Drug Loading) Fitting equation <![CDATA[R 2 ]]> Complete degradation time / week Comparative Example 1(0) y = -1.9159x + 170.2093 0.9854 88.84 Example 10 (1%) y = -1.8589x + 153.2114 0.9816 82.42 Example 11 (1.5%) y = -1.7404x + 154.4436 0.9486 88.74 Example 12 (2%) y = -2.1347x + 155.1874 0.9726 72.70 Example 13 (2.5%) y = -1.6872x + 150.1897 0.9694 89.02 Example 14 (3%) y = -1.1582x + 149.3309 0.9788 128.93

[0161] Combined with Table 8 and Figure 14 It can be seen that the drug-loaded suture provided by the present invention can regulate the degradation time by limiting the amount of drug loaded.

[0162] Effect of different drug loading on drug release performance:

[0163] The drug release performance was tested according to the above-mentioned method for detecting the effect of different polycaprolactone and polyglycolic acid ratios on drug release performance, and the drug release rates at different times were obtained. The results are listed in Table 9.

[0164] Table 9. Drug release rates of the drug-loaded sutures prepared in Examples 10, 12, and 14 at different time points.

[0165]

[0166] Based on Table 9, plot the cumulative drug release curves of the drug-loaded sutures prepared in Examples 10, 12, and 14 at different times, as shown. Figure 15 As shown.

[0167] Combining Table 9 and Figure 15 It can be seen that different drug loading capacities have a significant impact on the drug release of the cored yarn sutures. The cumulative drug release curve of the suture with a higher drug loading capacities has a steeper slope over the same time period compared to the curve with a lower drug loading capacities. This indicates that the higher drug loading capacities release the drug faster. This is partly because the sutures with higher drug loading capacities degrade faster, and partly because they carry more drug, resulting in a relatively larger release. Specifically, more drug is released from the nanofibers in the dermis, leading to a higher cumulative drug concentration in the environment. Figure 15 It can also be observed that the drug release rate is relatively fast in the first 10 hours of degradation. Furthermore, in the first 10 hours, the cumulative drug release rate of sutures with different drug loadings all reached more than 40%. After 24 hours, the drug release rate of the cored yarn sutures tended to be slow and stable, indicating that the prepared cored yarn sutures with different drug loadings have a good sustained-release effect.

[0168] Although the above embodiments have provided a detailed description of the present invention, they are only some embodiments of the present invention, and not all embodiments. People can obtain other embodiments based on these embodiments without creative effort, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A drug-loaded suture, characterized in that, The invention comprises a matrix and a drug loaded on the surface of the matrix; the matrix has a core-skin structure, wherein the core layer of the matrix is ​​polylactic acid filaments; the skin layer of the matrix is ​​a nanofiber membrane, wherein the nanofiber membrane is composed of polycaprolactone and polyglycolic acid; the polyglycolic acid accounts for 10-30% or 70-90% of the mass percentage of the nanofiber membrane; and the mass ratio of the core layer to the skin layer is 6-8:2-4. The mass ratio of the drug to the nanofiber membrane is 1~3:100; The method for preparing the drug-loaded suture includes the following steps: Polycaprolactone and polyglycolic acid were dissolved in a mixed solution of dichloromethane and N,N-dimethylformamide to obtain a matrix solution; The matrix solution and the drug are mixed to obtain a spinning solution; The drug-loaded suture is obtained by spinning polylactic acid filament as the core yarn using the spinning solution. The total mass percentage of polycaprolactone and polyglycolic acid in the matrix solution is 10-20%. The mass ratio of dichloromethane to N,N-dimethylformamide in the mixed solution of dichloromethane and N,N-dimethylformamide is 1:0.25~6; The spinning is electrospinning, and the voltage of the electrospinning is 12.5~20.5kV.

2. The drug-loaded suture according to claim 1, characterized in that, The drug in question is an antibacterial and anti-inflammatory drug.

3. A method for preparing the drug-loaded suture according to claim 1 or 2, comprising the following steps: Polycaprolactone and polyglycolic acid were dissolved in a mixed solution of dichloromethane and N,N-dimethylformamide to obtain a matrix solution; The matrix solution and the drug are mixed to obtain a spinning solution; The drug-loaded suture is obtained by spinning polylactic acid filament as the core yarn using the spinning solution. The total mass percentage of polycaprolactone and polyglycolic acid in the matrix solution is 10-20%. The mass ratio of dichloromethane to N,N-dimethylformamide in the mixed solution of dichloromethane and N,N-dimethylformamide is 1:0.25~6; The spinning is electrospinning, and the voltage of the electrospinning is 12.5~20.5kV.

4. The preparation method according to claim 3, characterized in that, The dissolution is carried out under stirring conditions, the stirring speed is 500~800 r / min, and the stirring time is 12~24 h.

5. The preparation method according to claim 3, characterized in that, The mixing is carried out under stirring conditions, the stirring speed is 500~800 r / min, and the stirring time is 8~20 h.

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