Absorbable antibacterial barb thread and preparation method thereof

Abstract

The invention relates to the technical field of barb threads, and particularly discloses an absorbable antibacterial barb thread and a preparation method thereof. An absorbable antibacterial barb line comprises a barb line body, and the barb line body is provided with a same-direction or reverse-direction barb structure. The gel layer is wrapped on the surface of the barb line; and the antibacterial layer is wrapped outside the gel layer. The preparation method comprises the following steps: S1, coating the gel layer: dipping the barb line in a gel solution, carrying out gelation treatment, and pulling out the barb line along the barb direction to obtain the barb line coated with the gel layer; s2, wrapping with an antibacterial layer. The antibacterial barb thread can be used for wound suture, weight reduction and thread embedding and the like, and has the advantages of being excellent in antibacterial performance, low in sensitivity and the like.

Description

Technical Field

[0001] This application relates to the technical field of barbed threads. More specifically, it relates to an absorbable antibacterial barbed thread and its preparation method. Background Art

[0002] The PDO barbed thread is made of polydioxanone, which is a synthetic absorbable material. After being implanted into the human body, it is gradually degraded into carbon dioxide and water through hydrolysis, without toxic residues and with excellent biocompatibility. Therefore, it has unparalleled advantages in the field of surgical suture, has received more and more attention, and has become the development direction of medical suture threads. The barbed thread mainly relies on the geometric barbed structure distributed on the surface to achieve higher tissue grasping force, so as to reduce the tension at the suture site.

[0003] Currently, the barbed thread has the following problems: due to the barbed structure, the barbed thread has a larger contact area with tissues, and it is more likely to cause incision infection. Since the barbed thread is sutured in the dermis layer, some patients may have a rejection reaction to the absorbable protein thread, resulting in incision swelling, exudation, etc. Therefore, it is of great significance to prepare a barbed thread with good biocompatibility, no adverse reactions in the human body, and long-lasting antibacterial properties. Summary of the Invention

[0004] In order to improve the biocompatibility and antibacterial properties of the barbed thread, this application provides an absorbable antibacterial barbed thread and its preparation method, and adopts the following technical solutions:

[0005] In the first aspect, this application provides an absorbable antibacterial barbed thread, including:

[0006] A barbed thread with a same-direction or reverse-direction barbed structure on it;

[0007] A gel layer wrapped on the surface of the barbed thread;

[0008] An antibacterial layer wrapped outside the gel layer.

[0009] By adopting the above technical solutions, preferably, a gel layer and an antibacterial layer are sequentially arranged outside the barbed thread. First, the gel layer has a structure similar to the human skin structure and has better compatibility with the human body, which can reduce the probability of the occurrence of rejection between the barbed thread and the skin.

[0010] Secondly, the setting of the gel layer can increase the thickness of the barbed thread, effectively improve the strength of the barbed thread, and reduce the possibility of the barbed thread breaking during the suture process.

[0011] Finally, an antibacterial layer is wrapped outside the gel layer. The antibacterial layer can make the barbed thread not easily contaminated and carry bacteria during use, and can continuously play an antibacterial effect after suture, effectively inhibiting phenomena such as wound swelling.

[0012] Optionally, the gel layer comprises a fibrin gel.

[0013] By adopting the above technical solution, when a wound heals, a blood clot is usually generated. The main constituent protein in the blood clot is fibrin. Preferably, a fibrin gel is used as the gel layer, which can reduce the rejection phenomenon and can reduce the formation of excessive fibrin at the wound to form a scar, being beneficial to the healing of the wound.

[0014] Optionally, the fibrin gel consists of fibrinogen and thrombin.

[0015] Optionally, the gel layer further comprises a polyacrylic acid hydrogel or a polypeptide hydrogel.

[0016] By adopting the above technical solution, preferably, a polyacrylic acid hydrogel or a polypeptide hydrogel is added to the gel layer. Both the polyacrylic acid hydrogel and the polypeptide hydrogel have relatively excellent water content and good compatibility with the skin, can cooperate with the fibrin gel to synergistically improve the mechanical strength of the barbed wire, and can further reduce the rejection phenomenon between the barbed wire and the skin.

[0017] Optionally, the antibacterial layer comprises an antibacterial inner layer and an antibacterial outer layer. The antibacterial inner layer comprises any one or more of gallic acid, catechin, ferulic acid, and caffeic acid.

[0018] By adopting the above technical solution, preferably, gallic acid, catechin, ferulic acid or caffeic acid is used as the antibacterial inner layer. Gallic acid etc. all have strong free radical scavenging effects, good antibacterial activities and the ability to chelate metal ions. After the antibacterial inner layer contacts with the gel layer, it can effectively inhibit the oxidation of the gel layer, thereby inhibiting the oxidation of the sulfhydryl groups and disulfide bonds of the proteins in the gel layer and maintaining the state and crosslinking ability of the proteins. At the same time, due to the high water content in the polyacrylic acid hydrogel and the polypeptide hydrogel, it can promote the dispersion of the antibacterial inner layer into the gel layer, and can further prevent the unfolding and change of the side chain structure of the protein, making the gel layer stable and playing a role in reducing the rejection reaction and reducing the formation of scars.

[0019] Optionally, the antibacterial outer layer comprises silk fibroin.

[0020] By adopting the above technical solution, silk fibroin has good biocompatibility and no obvious immunogenicity. Silk fibroin mainly has three secondary structures: helical structure, folded structure and random coil structure, and thus has excellent adsorption, bonding effects and crosslinked porous structures, and silk fibroin has excellent antibacterial properties. Using silk fibroin as the antibacterial outer layer can fully wrap the antibacterial inner layer and further improve the antibacterial effect of the barbed wire.

[0021] Optionally, the antibacterial outer layer further includes an additive, and the additive includes any one or more of berberine, gentamicin, and artemisinin.

[0022] By adopting the above technical solution, preferably, berberine, gentamicin, and artemisinin are used as additives and added to the antibacterial outer layer. The additives all have advantages such as good antibacterial effects and low toxicity, and can be loaded by the porous structure of silk fibroin, so that the additives can be slowly released from silk fibroin, thereby enabling the barbed wire to obtain a long-lasting antibacterial effect.

[0023] Through the setting of the antibacterial inner layer and the antibacterial outer layer, a double-layer antibacterial layer is obtained outside the barbed wire, which can greatly improve the antibacterial persistence of the barbed wire and enable the barbed wire to obtain a long-lasting antibacterial effect. The antibacterial inner layer inhibits the oxidation of the gel layer through free radical scavenging, enabling the gel layer to obtain lasting and stable low biocompatibility and strength. The setting of the antibacterial outer layer can not only wrap the antibacterial inner layer and the gel layer so that the antibacterial layer and the gel layer can firmly adhere to the surface of the barbed wire, but also introduce a potent antibacterial agent to further improve the strength of the barbed wire. Therefore, through the cooperation of the antibacterial inner layer and the antibacterial outer layer, the barbed wire obtains excellent and long-lasting antibacterial effects.

[0024] Optionally, the mass ratio of the silk fibroin to the additive is 10:0.5 - 1.5.

[0025] By adopting the above technical solution, the contents of the silk fibroin and the additive are optimized. Under the appropriate addition amount, the additive can be fully loaded by the silk fibroin and is not likely to block the porous structure of the silk fibroin, enabling the antibacterial outer layer to obtain excellent antibacterial properties and sustained release effects.

[0026] In a second aspect, the present application provides a preparation method for an absorbable antibacterial barbed wire, adopting the following technical solution:

[0027] A preparation method for an absorbable antibacterial barbed wire includes the following steps:

[0028] S1. Gel layer wrapping: Immerse the barbed wire in a gel solution, perform gelation treatment, and pull out the barbed wire along the barbed direction to obtain a barbed wire wrapped with a gel layer;

[0029] S2. Antibacterial layer wrapping: Coat an antibacterial solution on the barbed wire wrapped with the gel layer, repeat the coating, and dry to obtain an antibacterial barbed wire.

[0030] By adopting the above technical solution, the step of gel layer wrapping is optimized. Pulling out the barbed wire along the barbed direction is not likely to damage the barbed structure, and can also wrap the gel layer more evenly on the surface of the barbed wire, enabling the barbed wire to obtain stable mechanical strength.

[0031] Optionally, the number of times of repeated coating is 5 - 10 times.

[0032] By adopting the above technical solution and coating several times repeatedly, the thickness of the antibacterial layer is appropriate, which can achieve excellent antibacterial effects and can gradually dissolve and expose the gel layer, so that the gel layer can further promote wound healing.

[0033] In summary, the present application has the following beneficial effects:

[0034] 1. Since the present application preferably arranges a gel layer and an antibacterial layer in sequence outside the barbed wire. First of all, the gel layer has a structure similar to the human skin structure and has better compatibility with the human body, which can reduce the probability of the occurrence of rejection between the barbed wire and the skin. Secondly, the setting of the gel layer can increase the thickness of the barbed wire, effectively improve the strength of the barbed wire, and reduce the possibility of the barbed wire breaking during the suture process. Finally, an antibacterial layer is wrapped outside the gel layer. The antibacterial layer can make the barbed wire not easily contaminated and carry bacteria during use, and can continuously play an antibacterial effect after suture, effectively inhibiting phenomena such as wound swelling.

[0035] 2. When the wound in the present application heals, blood clots are usually generated. The main constituent protein in the blood clot is fibrin. Preferably using fibrin gel as the gel layer can reduce the rejection phenomenon and can reduce the formation of excessive fibrin at the wound to form scars, which is beneficial to wound healing.

[0036] 3. The present application preferably uses gallic acid, catechin, ferulic acid or caffeic acid as the antibacterial inner layer. Gallic acid and the like all have strong free radical scavenging effects, good antibacterial activities and the ability to chelate metal ions. After the antibacterial inner layer contacts the gel layer, it can effectively inhibit the oxidation of the gel layer, thereby inhibiting the oxidation of the sulfhydryl groups and disulfide bonds of the proteins in the gel layer and maintaining the state and crosslinking ability of the proteins. At the same time, due to the high water content in the acrylic hydrogel and the polypeptide hydrogel, it can promote the dispersion of the antibacterial inner layer into the gel layer, and can further prevent the side chain structure of the protein from unfolding and changing, etc., so that the gel layer can stably play the role of reducing the rejection reaction and reducing scar formation. Specific embodiments

[0037] The following further elaborates on the present application with reference to embodiments.

[0038] Preparation examples

[0039] Preparation example of acrylic hydrogel

[0040] Preparation example 1

[0041] Take a polyacrylic acid solution and a silk fibroin solution (mass fraction of 4%) and mix them in a mass ratio of 8:2 to obtain a mixed solution. Add 0.03 g of N,N'-methylenebisacrylamide to the mixed solution, stir well, defoam by ultrasonic treatment, and irradiate and cure under ultraviolet light with a wavelength of 365 nm at 500 mW / cm 2 to obtain a polyacrylic acid gel.

[0042] Preparation Example 2

[0043] First, weigh approximately 0.5 g of dichloro resin into a solid-phase synthesis tube, then add 10 mL of dichloromethane to the tube to fully swell the resin. After 5 minutes, squeeze out the solvent. Weigh 0.5 mmol of lysine (234 mg) into a vial, add 1 mmol of DIEA (200 μL) and 10 mL of dichloromethane to the vial to fully dissolve the amino acid, and then transfer it to the solid-phase synthesis tube for reaction for 2 hours. After the reaction, squeeze out the reaction solution, wash the resin with dichloromethane 5 times, with each washing time being 1 minute (the same hereinafter). Then add 10 mL of a pre-prepared blocking solution (DCM:CH3OH:DIEA = 17:2:1) to the synthesis tube to block the unreacted active chloride ions on the dichloro resin, and the blocking time is 30 minutes.

[0044] After blocking, first wash the resin with DCM 5 times, then wash the resin with DMF 5 times. Then use 10 mL of 20% piperidine (piperidine:DMF = 1:4) to remove the Fmoc protecting group on the amino acid, and react for 30 minutes. Drop the reacted 20% piperidine into clear water. If a large amount of white flocculent substances immediately appear, it indicates that the Fmoc has been removed. Wash the dichloro resin with DMF 5 times to remove the excess piperidine. Then weigh 1 mmol of tyrosine (459 mg) and 1 mmol of HBTU (379.25 mg) into a vial, add 2 mmol of DIEA (400 μL) and 10 mL of DMF to the vial and stir until the amino acid is completely dissolved, and then drop it into the solid-phase synthesis tube for reaction for 2 hours. Take 1 drop of the solvent in the synthesis tube and add it to a small amount of ninhydrin reagent, heat it in a water bath at 37 °C for 30 seconds, and observe the color change. If it is colorless or yellow, it indicates that the tyrosine residue has been successfully linked to the peptide chain. Wash the resin with DMF 5 times, and add 10 mL of 20% piperidine to the synthesis tube and react for 30 minutes to remove the Fmoc protecting group.

[0045] Repeat the above steps of DMF washing - amino acid reaction - Fmoc deprotection - DMF washing until the last serine. After deprotecting the Fmoc of the last serine, weigh 1 mmol of p-sulfobenzoic acid (202.18 mg) and 1 mmol of HBTU (379.25 mg) into a vial. Add 10 mL of DMF and 2 mmol of DIEA (400 μL) to the vial to fully dissolve p-sulfobenzoic acid, and then add it to the solid-phase synthesis tube for reaction overnight. After the reaction, wash the resin with DMF 5 times first, then wash the resin with DCM 5 times to remove the excess DMF. Finally, cut the peptide chain from the dichloro resin with 10 mL of pre-prepared 95% TFA (TFA:TIS:H2O = 95%:2.5%:2.5%), and the action time after adding TFA is 30 minutes. Transfer the solution containing the polypeptide chain cut by TFA to a pear-shaped flask, and use a rotary evaporator to vacuum evaporate to remove the TFA in the solution. During this period, rinse the solid-phase synthesis tube with DCM several times and transfer the rinsed solution to the pear-shaped flask for multiple evaporations until a viscous polypeptide solution is obtained. Add an appropriate amount of anhydrous ether to precipitate the polypeptide, let it stand for 30 minutes, then centrifuge and remove the supernatant to obtain the crude polypeptide product, which is stored at 4 °C for purification.

[0046] Purification: Dissolve the crude polypeptide product obtained by solid-phase synthesis with a small amount of DMSO and methanol solution to make its concentration 100 mg / mL. Filter the solution with a 0.22 μm filter membrane to remove impurities. Purify the polypeptide by high-performance liquid chromatography, with an injection volume of 100 μL each time, and the liquid phase program is 70 - 30 (70:95% H2O + 5% CH3OH + 0.05% TFA; 30:CH3OH + 0.05% TFA). Collect the solution at the sample peak with a pear-shaped flask, vacuum evaporate and then freeze-dry with a freeze dryer to obtain the pure polypeptide.

[0047] Mix 5 g of the pure polypeptide with 1 L of water and place it at room temperature to obtain a polypeptide hydrogel. It should be noted that the manganese source includes but is not limited to manganese carbonate, manganese dioxide, manganese phosphate, and manganese oxalate. At the same time, the manganese source can be a combination of one or more of the above materials.

[0048] Example

[0049] Example 1

[0050] On the one hand, the present application provides an absorbable antibacterial barbed wire, including:

[0051] A barbed wire with a same-direction or reverse-direction barbed structure on it;

[0052] A gel layer wrapped on the surface of the barbed wire;

[0053] An antibacterial layer, the antibacterial layer being wrapped outside the gel layer.

[0054] Among them, the gel layer is a fibrin gel layer, the antibacterial layer includes an antibacterial inner layer and an antibacterial outer layer, the antibacterial inner layer is gallic acid, and the antibacterial outer layer is silk fibroin.

[0055] On the other hand, the present application provides a preparation method of an absorbable antibacterial barbed wire, including the following steps:

[0056] S1. Gel layer wrapping: Mix fibrinogen at 3.5 mg / mL with thrombin at 10 IU / mL to obtain a fibrin gel solution; immerse the barbed wire in the gel solution, perform gelation treatment for 40 min, pull out the barbed wire along the barbed direction to obtain a barbed wire wrapped with a gel layer, and dry it to obtain a barbed wire wrapped with a gel layer;

[0057] S2. Antibacterial layer wrapping: First spray a gallic acid solution (the mass concentration of gallic acid is 0.2%) outside the barbed wire wrapped with a gel layer, spray it 3 times repeatedly, and dry it. Then brush a silk fibroin solution (7% w / v) on the surface of the barbed wire, brush it three times repeatedly, and dry it to obtain an antibacterial barbed wire.

[0058] Example 2

[0059] On the one hand, the present application provides an absorbable antibacterial barbed wire, including:

[0060] A barbed wire, the barbed wire having a same-direction or reverse-direction barbed structure;

[0061] A gel layer, the gel layer being wrapped on the surface of the barbed wire;

[0062] An antibacterial layer, the antibacterial layer being wrapped outside the gel layer.

[0063] Among them, the gel layer includes a fibrin gel layer and a hydrogel layer, the antibacterial layer includes an antibacterial inner layer and an antibacterial outer layer, the antibacterial inner layer is gallic acid, and the antibacterial outer layer is silk fibroin.

[0064] On the other hand, the present application provides a preparation method of an absorbable antibacterial barbed wire, including the following steps:

[0065] S1. Gel layer wrapping: Mix fibrinogen at 3.5 mg / mL with thrombin at 10 IU / mL to obtain a fibrin gel solution; immerse the barbed wire in the gel solution, perform gelation treatment for 40 min, pull out the barbed wire along the barbed direction to obtain an intermediate product, immerse the intermediate product in the acrylic hydrogel prepared in Preparation Example 1 for 20 min to obtain a barbed wire wrapped with a gel layer, and dry it to obtain a barbed wire wrapped with a gel layer;

[0066] S2. Antibacterial layer wrapping: First, spray gallic acid solution (the mass concentration of gallic acid is 0.2%) on the barbed wire wrapped with the gel layer, spray three times repeatedly, dry, then brush the silk fibroin solution (7% w / v) on the surface of the barbed wire, brush three times repeatedly, and dry to obtain the antibacterial barbed wire.

[0067] Example 3

[0068] On the one hand, the present application provides an absorbable antibacterial barbed wire, including:

[0069] A barbed wire with a same-direction or reverse-direction barbed structure on it;

[0070] A gel layer wrapped on the surface of the barbed wire;

[0071] An antibacterial layer wrapped outside the gel layer.

[0072] Among them, the gel layer includes a fibrin gel layer and a hydrogel layer, the antibacterial layer includes an antibacterial inner layer and an antibacterial outer layer, the antibacterial inner layer is gallic acid, and the antibacterial outer layer is silk fibroin.

[0073] On the other hand, the present application provides a preparation method of an absorbable antibacterial barbed wire, including the following steps:

[0074] S1. Gel layer wrapping: Mix fibrinogen at 3.5 mg / mL with thrombin at 10 IU / mL to obtain a fibrin gel solution; immerse the barbed wire in the gel solution, perform gelation treatment for 40 minutes, pull out the barbed wire along the barbed direction to obtain an intermediate product, immerse the intermediate product in the polypeptide hydrogel prepared in Preparation Example 2 for 20 minutes to obtain a barbed wire wrapped with a gel layer, and dry to obtain a barbed wire wrapped with a gel layer;

[0075] S2. Antibacterial layer wrapping: First, spray gallic acid solution (the mass concentration of gallic acid is 0.2%) on the barbed wire wrapped with the gel layer, spray three times repeatedly, dry, then brush the silk fibroin solution (7% w / v) on the surface of the barbed wire, brush three times repeatedly, and dry to obtain the antibacterial barbed wire.

[0076] Example 4

[0077] On the one hand, the present application provides an absorbable antibacterial barbed wire, including:

[0078] A barbed wire with a same-direction or reverse-direction barbed structure on it;

[0079] A gel layer wrapped on the surface of the barbed wire;

[0080] An antibacterial layer wrapped outside the gel layer.

[0081] Among them, the gel layer includes a fibrin gel layer and a hydrogel layer, the antibacterial layer includes an inner antibacterial layer and an outer antibacterial layer, the inner antibacterial layer is gallic acid, and the outer antibacterial layer is silk fibroin.

[0082] On the other hand, the present application provides a preparation method of an absorbable antibacterial barbed wire, including the following steps:

[0083] S1. Gel layer wrapping: Mix fibrinogen at 3.5 mg / mL with thrombin at 10 IU / mL to obtain a fibrin gel solution; immerse the barbed wire in the gel solution, perform gelation treatment for 40 min, pull out the barbed wire along the direction of the barbs to obtain an intermediate product, immerse the intermediate product in the acrylic hydrogel prepared in Preparation Example 1 for 20 min to obtain a barbed wire wrapped with a gel layer, and dry it to obtain a barbed wire wrapped with a gel layer;

[0084] S2. Antibacterial layer wrapping: First spray a gallic acid solution (the mass concentration of gallic acid is 0.2%) on the barbed wire wrapped with the gel layer, spray it 3 times repeatedly, and dry it. Then brush the outer antibacterial layer solution on the surface of the barbed wire, brush it three times repeatedly, and dry it to obtain an antibacterial barbed wire.

[0085] Preparation of the outer antibacterial layer solution: Mix berberine powder with water to obtain a berberine solution at 4 mg / mL, mix silk fibroin with water to prepare a 7% (w / v) silk fibroin solution, then add glycerol to the silk fibroin solution, and the mass ratio of glycerol is 30%. Mix the berberine solution and the silk fibroin solution so that the mass ratio of berberine to silk fibroin is 0.5:10 to obtain the outer antibacterial layer solution.

[0086] Example 5

[0087] On the one hand, the present application provides an absorbable antibacterial barbed wire, including:

[0088] A barbed wire with a same-direction or reverse-direction barb structure on the barbed wire;

[0089] A gel layer wrapped on the surface of the barbed wire;

[0090] An antibacterial layer wrapped outside the gel layer.

[0091] Among them, the gel layer is a fibrin gel layer, the antibacterial layer includes an inner antibacterial layer and an outer antibacterial layer, the inner antibacterial layer is gallic acid, and the outer antibacterial layer is silk fibroin.

[0092] On the other hand, the present application provides a preparation method of an absorbable antibacterial barbed wire, including the following steps:

[0093] S1. Gel layer wrapping: Mix fibrinogen at 3.5 mg / mL with thrombin at 10 IU / mL to obtain a fibrin gel solution; Immerse the barbed wire in the gel solution, conduct gelation treatment for 40 min, pull out the barbed wire along the barbed direction to obtain an intermediate product, immerse the intermediate product in the acrylic hydrogel prepared in Preparation Example 1 for 20 min to obtain a barbed wire wrapped with a gel layer, and dry it to obtain a barbed wire wrapped with a gel layer;

[0094] S2. Antibacterial layer wrapping: First spray gallic acid solution (the mass concentration of gallic acid is 0.2%) on the barbed wire wrapped with a gel layer, repeat spraying 3 times, and dry it. Brush the antibacterial outer layer solution on the surface of the barbed wire, repeat brushing three times, and dry it to obtain an antibacterial barbed wire.

[0095] Preparation of the antibacterial outer layer solution: Mix berberine powder with water to obtain a berberine solution at 4 mg / mL, mix silk fibroin with water to prepare a 7% (w / v) silk fibroin solution, then add glycerol to the silk fibroin solution, and the mass ratio of glycerol is 30%. Mix the berberine solution and the silk fibroin solution so that the mass ratio of berberine to silk fibroin is 1:10 to obtain the antibacterial outer layer solution.

[0096] Example 6

[0097] On the one hand, the present application provides an absorbable antibacterial barbed wire, including:

[0098] A barbed wire with a same-direction or reverse-direction barbed structure on it;

[0099] A gel layer wrapped on the surface of the barbed wire;

[0100] An antibacterial layer wrapped outside the gel layer.

[0101] Among them, the gel layer is a fibrin gel layer, the antibacterial layer includes an antibacterial inner layer and an antibacterial outer layer, the antibacterial inner layer is gallic acid, and the antibacterial outer layer is silk fibroin.

[0102] On the other hand, the present application provides a preparation method for an absorbable antibacterial barbed wire, including the following steps:

[0103] S1. Gel layer wrapping: Mix fibrinogen at 3.5 mg / mL with thrombin at 10 IU / mL to obtain a fibrin gel solution; Immerse the barbed wire in the gel solution, conduct gelation treatment for 40 min, pull out the barbed wire along the barbed direction to obtain an intermediate product, immerse the intermediate product in the acrylic hydrogel prepared in Preparation Example 1 for 20 min to obtain a barbed wire wrapped with a gel layer, and dry it to obtain a barbed wire wrapped with a gel layer;

[0104] S2. Antibacterial layer wrapping: First, spray gallic acid solution (the mass concentration of gallic acid is 0.2%) outside the barbed wire wrapped with the gel layer, spray three times repeatedly, dry, brush the antibacterial outer layer solution on the surface of the barbed wire, brush three times repeatedly, and dry to obtain the antibacterial barbed wire.

[0105] Preparation of the antibacterial outer layer solution: Mix berberine powder with water to obtain a berberine solution with a concentration of 4 mg / mL. Mix silk fibroin with water to prepare a 7% (w / v) silk fibroin solution, and then add glycerol to the silk fibroin solution, with the mass ratio of glycerol being 30%. Mix the berberine solution and the silk fibroin solution so that the mass ratio of berberine to silk fibroin is 1.5:10 to obtain the antibacterial outer layer solution.

[0106] Example 7

[0107] On the one hand, the present application provides an absorbable antibacterial barbed wire, including:

[0108] A barbed wire with a same-direction or reverse-direction barbed structure on it;

[0109] A gel layer wrapped on the surface of the barbed wire;

[0110] An antibacterial layer wrapped outside the gel layer.

[0111] Among them, the gel layer is a fibrin gel layer, the antibacterial layer includes an antibacterial inner layer and an antibacterial outer layer, the antibacterial inner layer is gallic acid, and the antibacterial outer layer is silk fibroin.

[0112] On the other hand, the present application provides a preparation method for an absorbable antibacterial barbed wire, including the following steps:

[0113] S1. Gel layer wrapping: Mix fibrinogen with a concentration of 3.5 mg / mL and thrombin with 10 IU / mL to obtain a fibrin gel solution; immerse the barbed wire in the gel solution, perform gelation treatment for 40 minutes, pull out the barbed wire along the barbed direction to obtain an intermediate product, immerse the intermediate product in the acrylic hydrogel prepared in Preparation Example 1 for 20 minutes to obtain a barbed wire wrapped with a gel layer, and dry to obtain a barbed wire wrapped with a gel layer;

[0114] S2. Antibacterial layer wrapping: First, spray ferulic acid solution (the mass concentration of ferulic acid is 0.2%) outside the barbed wire wrapped with the gel layer, spray three times repeatedly, dry, brush the antibacterial outer layer solution on the surface of the barbed wire, brush three times repeatedly, and dry to obtain the antibacterial barbed wire.

[0115] Preparation of the antibacterial outer layer solution: Gentamicin powder was mixed with water to obtain a 4 mg / mL gentamicin solution. Silk fibroin was mixed with water to prepare a 7% (w / v) silk fibroin solution. The gentamicin solution and the silk fibroin solution were mixed so that the mass ratio of gentamicin to silk fibroin was 1.5:10, obtaining the antibacterial outer layer solution.

[0116] Comparative example

[0117] Comparative example 1

[0118] The difference between this comparative example and Example 1 is that no gel layer was set in this comparative example, and an antibacterial barbed wire was prepared.

[0119] Comparative example 2

[0120] The difference between this comparative example and Example 1 is that no antibacterial layer was set in this comparative example.

[0121] Comparative example 3

[0122] The difference between this comparative example and Example 1 is that no antibacterial inner layer was set in this comparative example.

[0123] Performance detection test

[0124] (1) Viscosity test: Different suture samples were cut into 200 mm in length, and an Instron material testing machine was used to test the tensile and knotting strengths of the sutures. For the tensile strength test, the sample was clamped at both ends of the material testing machine, the tensile speed was 300 mm / min, the clamping length was set to 125 mm, the test environmental temperature: 20 ± 2°C, relative humidity: 65 ± 2%; for the knotting strength test, a simple free knot needed to be tied for the test sample, the sample was clamped at both ends of the material testing machine, the free knot was in the middle of the two chucks, and the suture between the chucks was tightened, the tensile speed was 300 mm / min, the clamping length was set to 125 mm, the test environmental temperature: 20 ± 2°C, relative humidity: 65 ± 2%.

[0125] (2) Antibacterial performance: Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli were selected as the test bacteria species. Evaluation was carried out according to the antibacterial activity, and the evaluation standard was ISO20645:2004. The experimental method was to cut different suture samples into 5 cm in length, inoculate about 1 mL of bacterial suspension (1×108 CFU / mL) on the agar culture plate for the sample, and place it in an incubator at 37°C for 18 - 24 h. If the inhibitory concentration was reached, there would be no growth of microorganisms, and an obvious antibacterial zone would appear around the circular sample.

[0126] Table 1 Performance detection

[0127]

[0128] Similarly, the barbed wire in Example 1 was tested for cytocompatibility (live / dead cell staining test). Within 2 days, there was a trend of increased cell proliferation and no difference in viability. The barbed wire in Comparative Example 1 was tested for cytocompatibility (live / dead cell staining test). Within 2 days, there was a trend of increased cell proliferation and there were certain differences in viability. Compared with the barbed wire in Example 1, the cell viability was poorer.

[0129] Combined with the performance detection and comparison in Table 1, it can be found that:

[0130] 1. By comparing Example 1 with Comparative Examples 1-2, it can be found that: the antibacterial effect and mechanical strength of the barbed wire prepared in Example 1 have both increased. This shows that in this application, the gel layer has a structure similar to the human skin structure and has better compatibility with the human body, which can reduce the probability of the occurrence of rejection between the barbed wire and the skin; secondly, the setting of the gel layer can increase the thickness of the barbed wire, effectively improve the strength of the barbed wire, and reduce the possibility of the barbed wire breaking during the suture process. Finally, an antibacterial layer is wrapped outside the gel layer. The antibacterial layer can make the barbed wire not easily contaminated and carry bacteria during use, and can continuously play an antibacterial effect after suture, effectively inhibiting phenomena such as wound swelling.

[0131] 2. By comparing Examples 2-3 with Example 1, it can be found that: the mechanical strength of the barbed wire prepared in Examples 2-3 has both increased. This shows that in this application, it is preferred to add acrylic hydrogel or polypeptide hydrogel to the gel layer. Both acrylic hydrogel and polypeptide hydrogel have relatively excellent water content and good compatibility with the skin, can cooperate with fibrin gel to synergistically improve the mechanical strength of the barbed wire, and can further reduce the rejection phenomenon between the barbed wire and the skin.

[0132] 3. By comparing Examples 4-6 with Example 1, it can be found that: the antibacterial performance of the barbed wire prepared in Examples 4-6 has both increased. This shows that in this application, it is preferred to use berberine, gentamicin, and artemisinin as additives and add them to the antibacterial outer layer. The additives all have advantages such as good antibacterial effects and low toxicity, and can be loaded by the porous structure of silk fibroin, so that the additives can be slowly released from the silk fibroin, so that the barbed wire can obtain a long-term antibacterial effect.

[0133] 4. By comparing Example 7 with Example 1, it can be found that: the mechanical strength of the barbed wire prepared in Example 1 has decreased. This shows that in this application, it is preferred to add glycerol to the antibacterial outer layer. The presence of glycerol can promote the formation of the folded structure in silk fibroin, improve the loading amount and loading effect of silk fibroin on antibacterial materials such as berberine.

[0134] This specific embodiment is only an interpretation of the present application and does not limit the present application. After reading this specification, those skilled in the art can make modifications to this embodiment without creative contributions as needed, but as long as it is within the scope of the claims of the present application, it is protected by the patent law.

Claims

1. An absorbable antibacterial barbed thread, characterized in that: include: Barbed wire, wherein the barbed wire has a same-direction or reverse-direction barb structure; a gel layer, the gel layer being wrapped around the surface of the barbed wire; An antibacterial layer is wrapped around the gel layer.

2. The absorbable antibacterial barbed thread according to claim 1, characterized in that: The gel layer includes fibrin gel.

3. The absorbable antibacterial barbed thread according to claim 2, characterized in that: The fibrin gel is composed of fibrinogen and thrombin.

4. The absorbable antibacterial barbed thread according to claim 3, characterized in that: The gel layer further comprises polyacrylic acid hydrogel or polypeptide hydrogel.

5. The absorbable antibacterial barbed thread according to claim 1, characterized in that: The antibacterial layer includes an antibacterial inner layer and an antibacterial outer layer. The antibacterial inner layer includes any one or more of gallic acid, catechin, ferulic acid, and caffeic acid.

6. The absorbable antibacterial barbed thread according to claim 5, characterized in that: The antimicrobial outer layer includes silk fibroin.

7. The absorbable antibacterial barbed thread according to claim 6, characterized in that: The antibacterial outer layer further comprises additives, and the additives comprise any one or more of berberine, gentamicin, and artemisinin.

8. The absorbable antibacterial barbed thread according to claim 7, characterized in that: The mass ratio of the silk fibroin to the additive is 10:0.5-1.

5.

9. The method for preparing an absorbable antibacterial barbed thread according to any one of claims 1 to 8, characterized in that: The following steps are involved: S1, gel layer wrapping: immersing the barbed wire in a gel solution, gelling the barbed wire, and pulling the barbed wire along the barb direction to obtain a barbed wire wrapped with a gel layer; S2. Antibacterial layer wrapping: coating the outside of the barbed wire wrapped with the gel layer with an antibacterial solution, repeating the coating, and drying to obtain an antibacterial barbed wire.

10. The absorbable antibacterial barbed thread according to claim 9, characterized in that: The number of repeated coatings is 5-10 times.

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