Absorbable antibacterial barbed suture and preparation method thereof

Abstract

The application relates to the technical field of barbed wires, and particularly discloses absorbable antibacterial barbed wire and a preparation method thereof. The absorbable antibacterial barbed wire comprises a barbed wire, which is provided with same-direction or reverse barb structures; a gel layer, which is wrapped on the surface of the barbed wire; and an antibacterial layer, which is wrapped outside the gel layer. The preparation method comprises the following steps: S1, gel layer wrapping: the barbed wire is immersed in a gel solution, gelatinization treatment is carried out, the barbed wire is pulled out along the barb direction, and the barbed wire wrapped with the gel layer is obtained; and S2, antibacterial layer wrapping. The antibacterial barbed wire can be used for wound suture, weight reduction buried line and the like, and has the advantages of excellent antibacterial performance, low sensitivity and the like.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of barbed wire, more particularly, it relates to an absorbable antibacterial barbed wire and a preparation method thereof. BACKGROUND

[0002] PDO barbed wire 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 has excellent biocompatibility. Therefore, it has unparalleled advantages in surgical suturing, receives more and more attention, and becomes the development direction of medical suturing thread. Barbed wire mainly relies on the geometric barb structure distributed on the surface to achieve higher tissue holding force, so as to reduce the tension at the suture.

[0003] At present, the barbed wire has the following problems: due to the barb structure, the contact area between the barbed wire and the tissue is larger, and incision infection is more likely to occur. Since the barbed wire is sutured in the dermis layer, some patients may have rejection reaction to absorbable protein thread, causing incision redness, exudation, etc. Therefore, it is of great significance to prepare barbed wire with good biocompatibility, no adverse reaction in the human body, and persistent antibacterial property. SUMMARY

[0004] In order to improve the biocompatibility and antibacterial property of the barbed wire, the present application provides an absorbable antibacterial barbed wire and a preparation method thereof, which adopts the following technical scheme:

[0005] In a first aspect, the present application provides an absorbable antibacterial barbed wire, comprising:

[0006] The barbed wire has same or opposite barb structure on the surface;

[0007] The gel layer is wrapped on the surface of the barbed wire;

[0008] The antibacterial layer is wrapped outside the gel layer.

[0009] By adopting the above technical scheme, preferably, the gel layer and the antibacterial layer are sequentially arranged outside the barbed wire. First, the gel layer has a structure similar to that of human skin, has good compatibility with the human body, and can reduce the probability of rejection between the barbed wire and the skin;

[0010] 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 breaking of the barbed wire during suturing.

[0011] Finally, the antibacterial layer is wrapped outside the gel layer. The antibacterial layer can prevent the barbed wire from being contaminated and carrying bacteria during use, and can continuously play an antibacterial effect after suturing, effectively inhibiting the redness of the wound.

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

[0013] By adopting the above technical scheme, when the wound heals, blood clots are usually generated, the main component protein in the blood clots is fibrin, and the fibrin gel is preferably adopted as the gel layer, so that the rejection phenomenon can be reduced, and too much fibrin is prevented from being generated at the wound to form a scar, thereby facilitating the healing of the wound.

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

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

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

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

[0018] By adopting the above technical scheme, gallic acid, catechin, ferulic acid or coffee acid is preferably adopted as the antibacterial inner layer, gallic acid and the like have strong free radical scavenging effect, good antibacterial activity and the ability to chelate metal ions, after the antibacterial inner layer contacts the gel layer, the oxidation of the gel layer can be effectively inhibited, so that the oxidation of the sulfhydryl and disulfide bond of the protein in the gel layer is inhibited, the state and cross-linking ability of the protein are maintained. At the same time, due to the high water content in the polyacrylic hydrogel and the polypeptide hydrogel, the antibacterial inner layer can be dispersed into the gel layer, which can further hinder the unfolding and change of the side chain structure of the protein, so as to stabilize the gel layer and reduce the rejection reaction and the formation of a scar.

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

[0020] By adopting the above technical scheme, the silk fibroin has good biocompatibility and no obvious immunogenicity. The silk fibroin mainly has three secondary structures: helical structure, folded structure and random coil structure, thereby having excellent adsorption, bonding effect and cross-linked porous structure, and the silk fibroin has excellent antibacterial performance. The silk fibroin is used as the antibacterial outer layer, can fully wrap the antibacterial inner layer, and further improves the antibacterial effect of the barbed line.

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

[0022] By adopting the above technical solution, preferably berberine, gentamicin, and artemisinin are added as additives to the antibacterial outer layer, and the additives have good antibacterial effect, low toxicity, and the like, and can be loaded by the porous structure of silk fibroin, so that the additives can be slowly released from the silk fibroin, thereby enabling the barbed suture to have long-acting antibacterial effect.

[0023] By arranging the antibacterial inner layer and the antibacterial outer layer, the barbed suture is provided with a double-layer antibacterial layer, which can greatly improve the antibacterial durability of the barbed suture and enable the barbed suture to have long-acting antibacterial effect. The antibacterial inner layer inhibits oxidation of the gel layer by free radical scavenging, so that the gel layer has persistent and stable low rejection and strength. The arrangement of the antibacterial outer layer not only enables the antibacterial layer and the gel layer to be firmly attached to the surface of the barbed suture, but also introduces a strong antibacterial agent, thereby further improving the strength of the barbed suture. Therefore, by cooperation of the antibacterial inner layer and the antibacterial outer layer, the barbed suture has excellent and long-acting antibacterial effect.

[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 content of the silk fibroin and the additive is optimized. Under a suitable additive amount, the additive can be fully loaded by the silk fibroin, and the porous structure of the silk fibroin is not easily blocked, so that the antibacterial outer layer has excellent antibacterial property and slow-release effect.

[0026] In a second aspect, the application provides a preparation method of the absorbable antibacterial barbed suture, which adopts the following technical solution:

[0027] The preparation method of the absorbable antibacterial barbed suture comprises the following steps:

[0028] S1, gel layer wrapping: dipping the barbed suture in a gel solution, gelatinizing, and pulling out the barbed suture in the barb direction to obtain the barbed suture wrapped with a gel layer;

[0029] S2, antibacterial layer wrapping: coating an antibacterial solution on the barbed suture wrapped with the gel layer, repeating the coating, and drying to obtain the antibacterial barbed suture.

[0030] By adopting the above technical solution, the step of wrapping the gel layer is optimized. The barbed suture is pulled out in the barb direction, so that the barb structure is not easily damaged, and the gel layer can be uniformly wrapped on the surface of the barbed suture, thereby enabling the barbed suture to have stable mechanical strength.

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

[0032] By adopting the technical scheme, the thickness of the antibacterial layer is appropriate after repeated coating several times, excellent antibacterial effect can be achieved, and the exposed gel layer can be gradually dissolved to further promote wound healing.

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

[0034] 1. Since the present application preferably adopts a gel layer and an antibacterial layer arranged in turn outside the barbed suture, firstly, the gel layer has a structure similar to that of human skin, has good compatibility with the human body, and can reduce the probability of occurrence of rejection between the barbed suture and the skin; secondly, the setting of the gel layer can increase the thickness of the barbed suture, effectively improve the strength of the barbed suture, and reduce the possibility of breakage of the barbed suture during suturing. Finally, the antibacterial layer wrapped outside the gel layer can make the barbed suture not easy to be contaminated and carry bacteria during use, and can continuously play an antibacterial effect after suturing, effectively inhibiting the occurrence of redness and other phenomena in the wound.

[0035] 2. In the present application, when the wound heals, blood clots are usually produced, and the main component protein in the blood clots is fibrin. Preferably, fibrin gel is used as the gel layer, which can reduce rejection and reduce the formation of scars due to excessive fibrin in the wound, which is beneficial to wound healing.

[0036] 3. The present application preferably uses gallic acid, catechin, ferulic acid or coffee acid as the antibacterial inner layer. Gallic acid and the like have strong free radical scavenging effect, good antibacterial activity and 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 and disulfide bond of the protein in the gel layer, maintaining the state and cross-linking ability of the protein. At the same time, since the water content in the acrylic acid hydrogel and the polypeptide hydrogel is high, the antibacterial inner layer can be dispersed into the gel layer, which can further hinder the unfolding and change of the side chain structure of the protein, so as to stabilize the gel layer and reduce rejection and scar formation. DETAILED DESCRIPTION

[0037] The present application will be further described in detail below in combination with examples.

[0038] Preparation Example

[0039] Preparation Example of Acrylic Acid Hydrogel

[0040] Preparation Example 1

[0041] The polyacrylic acid solution and the silk fibroin solution (mass fraction of 4%) were mixed in a mass ratio of 8:2 to obtain a mixed solution, 0.03 g of N,N'-methylenebisacrylamide was added to the mixed solution, and the mixture was stirred thoroughly, defoamed by ultrasonic, and cured by irradiation of ultraviolet light at a wavelength of 365 nm and a power of 500 mW / cm 2 to obtain a polyacrylic acid gel.

[0042] Preparation Example 2

[0043] First, about 0.5 g of dichloride resin was weighed on an electronic balance in a solid-phase synthesis tube, and then 10 mL of dichloromethane was added to the resin to swell the resin fully, and the solvent was squeezed out after 5 minutes. 0.5 mmol of lysine (234 mg) was weighed on an electronic balance in a Schlenk flask, 1 mmol of DIEA (200 μL) and 10 mL of dichloromethane were added to the flask to dissolve the amino acid fully, and then the mixture was transferred to the solid-phase synthesis tube for reaction for 2 hours. After the reaction was completed, the reaction solution was squeezed out, and the resin was washed with dichloromethane for 5 times, each time for 1 minute (the same below), and then 10 mL of a blocking solution (DCM:CH3OH:DIEA=17:2:1) prepared in advance was added to the synthesis tube to block the active chlorine ions on the dichloride resin that were not completely reacted, and the blocking was performed for 30 minutes.

[0044] After the blocking was completed, the resin was washed with DCM for 5 times, and then washed with DMF for 5 times, and then 10 mL of 20% piperidine (piperidine:DMF=1:4) was used to remove the Fmoc protecting group on the amino acid, and the reaction was performed for 30 minutes. The 20% piperidine after the reaction was added dropwise to clear water, and a large amount of white flocculent substance was immediately generated, indicating that the Fmoc was removed. The dichloride resin was washed with DMF for 5 times to remove the excess piperidine, and then 1 mmol of tyrosine (459 mg) and 1 mmol of HBTU (379.25 mg) were weighed on an electronic balance in a Schlenk flask, 2 mmol of DIEA (400 μL) and 10 mL of DMF were added to the flask, and the mixture was stirred until the amino acid was dissolved completely, and then the mixture was added dropwise to the solid-phase synthesis tube, and the reaction was performed for 2 hours. One drop of the solvent in the synthesis tube was added to a small amount of ninhydrin reagent, heated in a 37°C water bath for 30 seconds, and the color change was observed. If the color was colorless or yellow, it indicated that the tyrosine residue was successfully connected to the peptide chain. The resin was washed with DMF for 5 times, 10 mL of 20% piperidine was added dropwise to the synthesis tube, and the Fmoc protecting group was removed by reaction for 30 minutes.

[0045] The above-mentioned DMF washing-amino acid reaction-Fmoc deprotection-DMF washing steps were repeated until the last serine. After the Fmoc of the last serine was removed, 1 mmol of p-toluenesulfonic acid (202.18 mg) and 1 mmol of HBTU (379.25 mg) were weighed in a vial, 10 mL of DMF and 2 mmol of DIEA (400 μL) were added to the vial to dissolve the p-toluenesulfonic acid, and then added to the solid-phase synthesis tube for overnight reaction. After the reaction was completed, the resin was first washed with DMF for 5 times, and then washed with DCM for 5 times to remove the excess DMF, and finally 10 mL of 95% TFA (TFA: TIS: H2O = 95%: 2.5%: 2.5%) prepared in advance was used to cut the peptide chain from the dichloromethane resin, and the reaction time after adding TFA was 30 minutes. The solution containing the polypeptide chain cut by TFA was transferred to a flask, and a rotary evaporator was used to remove TFA in the solution under vacuum, and the solid-phase synthesis tube was rinsed with DCM for several times, and the rinsed solution was transferred to the flask for several times of rotary evaporation until a viscous polypeptide solution was obtained. An appropriate amount of anhydrous ether was added to precipitate the polypeptide, and after standing for 30 minutes, centrifugation was performed and the supernatant was removed to obtain a crude polypeptide product, which was stored at 4°C for purification.

[0046] Purification: The crude polypeptide product obtained by solid-phase synthesis was dissolved in a small amount of DMSO and methanol solution to make its concentration 100 mg / mL. The solution was filtered with a 0.22 μm filter membrane to remove impurities. High performance liquid chromatography was used for purification of the polypeptide, and the sample injection amount was 100 μL each time. The liquid phase program was 70-30 (70: 95% H2O + 5% CH3OH + 0.05% TFA; 30: CH3OH + 0.05% TFA). The solution at the sample peak was collected with a flask, vacuum evaporated, and then freeze-dried to obtain a pure polypeptide product.

[0047] 5 g of the pure polypeptide product was mixed with 1 L of water and placed at room temperature to obtain a polypeptide hydrogel. It is worth noting that the manganese source includes but is not limited to manganese carbonate, manganese dioxide, manganese phosphate, and manganese oxalate, and the manganese source can be a combination of one or more of the above materials.

[0048] Example

[0049] Example 1

[0050] In one aspect, the present application provides an absorbable antibacterial barbed wire, comprising:

[0051] The barbed wire has same-direction or reverse barb structures on the surface of the barbed wire;

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

[0053] an antibacterial layer, which is wrapped outside the gel layer.

[0054] The gel layer is a fibrin gel layer, the antibacterial layer comprises 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] In another aspect, the application provides a preparation method of the absorbable antibacterial barbed wire, comprising the following steps:

[0056] S1, gel layer wrapping: 3.5 mg / mL fibrinogen and 10 IU / mL thrombin are mixed to obtain a fibrin gel solution; the barbed wire is immersed in the gel solution, and the barbed wire is pulled out along the barb direction after gelation treatment for 40 min to obtain the barbed wire wrapped with the gel layer, which is dried to obtain the barbed wire wrapped with the gel layer;

[0057] S2, antibacterial layer wrapping: gallic acid solution (0.2% gallic acid) is first sprayed on the barbed wire wrapped with the gel layer, and the spraying is repeated for three times, and then the silk fibroin solution (7% w / v) is brushed on the surface of the barbed wire, and the brushing is repeated for three times, and then the barbed wire is dried to obtain the antibacterial barbed wire.

[0058] Example 2

[0059] In one aspect, the application provides an absorbable antibacterial barbed wire, comprising:

[0060] a barbed wire, which has same-direction or reverse barb structures on the barbed wire;

[0061] a gel layer, which is wrapped on the surface of the barbed wire;

[0062] an antibacterial layer, which is wrapped outside the gel layer.

[0063] The gel layer comprises a fibrin gel layer and a hydrogel layer, the antibacterial layer comprises 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] In another aspect, the application provides a preparation method of the absorbable antibacterial barbed wire, comprising the following steps:

[0065] S1, gel layer wrapping: 3.5 mg / mL fibrinogen and 10 IU / mL thrombin are mixed to obtain a fibrin gel solution; the barbed wire is immersed in the gel solution, and the barbed wire is pulled out along the barb direction after gelation treatment for 40 min to obtain the barbed wire wrapped with the gel layer, which is dried to obtain the barbed wire wrapped with the gel layer;

[0066] S2, antibacterial layer wrapping: first spray gallic acid solution (0.2% mass concentration of gallic acid) on the barbed wire wrapped with the gel layer, repeat spraying 3 times, dry, brush silk fibroin solution (7% w / v) on the surface of the barbed wire, repeat brushing three times, dry, to get antibacterial barbed wire.

[0067] Example 3

[0068] In one aspect, the application provides an absorbable antibacterial barbed wire, comprising:

[0069] The barbed wire has a same direction or reverse barbed structure on the barbed wire;

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

[0071] The antibacterial layer is wrapped outside the gel layer.

[0072] Wherein, the gel layer is a gel layer comprising a fibrin gel layer and a hydrogel layer, the antibacterial layer comprises 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] In another aspect, the application provides a preparation method of an absorbable antibacterial barbed wire, comprising the following steps:

[0074] S1, gel layer wrapping: mix 3.5 mg / mL fibrinogen with 10 IU / mL thrombin to obtain a fibrin gel solution; immerse the barbed wire in the gel solution, gelatinize for 40 min, pull out the barbed wire along the barbed direction, obtain an intermediate product, immerse the intermediate product in the polypeptide hydrogel prepared in Preparation Example 2, immerse for 20 min, obtain the barbed wire wrapped with the gel layer, dry, obtain the barbed wire wrapped with the gel layer;

[0075] S2, antibacterial layer wrapping: first spray gallic acid solution (0.2% mass concentration of gallic acid) on the barbed wire wrapped with the gel layer, repeat spraying 3 times, dry, brush silk fibroin solution (7% w / v) on the surface of the barbed wire, repeat brushing three times, dry, to get antibacterial barbed wire.

[0076] Example 4

[0077] In one aspect, the application provides an absorbable antibacterial barbed wire, comprising:

[0078] The barbed wire has a same direction or reverse barbed structure on the barbed wire;

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

[0080] The antibacterial layer is wrapped outside the gel layer.

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

[0082] In another aspect, the application provides a preparation method of the absorbable antibacterial barbed wire, comprising the following steps:

[0083] S1, gel layer wrapping: 3.5 mg / mL fibrinogen is mixed with 10 IU / mL thrombin to obtain a fibrin gel solution; the barbed wire is immersed in the gel solution, and the gelation treatment is performed for 40 min, the barbed wire is pulled out along the barb direction to obtain an intermediate product, the intermediate product is immersed in the acrylic acid hydrogel prepared in Preparation Example 1 for 20 min to obtain the barbed wire wrapped with the gel layer, and the barbed wire wrapped with the gel layer is dried.

[0084] S2, antibacterial layer wrapping: gallic acid solution (the mass concentration of gallic acid is 0.2%) is first sprayed on the barbed wire wrapped with the gel layer, the spraying is repeated for three times, and the antibacterial outer layer solution is brushed on the surface of the barbed wire, the brushing is repeated for three times, and the antibacterial barbed wire is obtained after drying.

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

[0086] Example 5

[0087] In one aspect, the application provides an absorbable antibacterial barbed wire, comprising:

[0088] The barbed wire has a same-direction or reverse barb structure.

[0089] The gel layer is wrapped on the surface of the barbed wire.

[0090] The antibacterial layer is wrapped outside the gel layer.

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

[0092] In another aspect, the application provides a preparation method of the absorbable antibacterial barbed wire, comprising the following steps:

[0093] S1, gel layer wrapping: 3.5 mg / mL fibrinogen and 10 IU / mL thrombin were mixed to obtain a fibrin gel solution; the barbed wire was immersed in the gel solution, and the gel was treated for 40 min, then the barbed wire was pulled out along the barb direction to obtain an intermediate product, the intermediate product was immersed in the acrylic hydrogel prepared in Preparation Example 1 for 20 min to obtain a barbed wire wrapped with a gel layer, and then dried to obtain a barbed wire wrapped with a gel layer;

[0094] S2, antibacterial layer wrapping: gallic acid solution (0.2% gallic acid) was first sprayed on the barbed wire wrapped with a gel layer, repeated 3 times, dried, and then an antibacterial outer layer solution was brushed on the surface of the barbed wire, repeated 3 times, dried, to obtain an antibacterial barbed wire.

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

[0096] Example 6

[0097] In one aspect, the present application provides an absorbable antibacterial barbed wire, comprising:

[0098] a barbed wire having same-direction or reverse barb structures on the surface of the barbed wire;

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

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

[0101] The gel layer is a fibrin gel layer, the antibacterial layer comprises 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] In another aspect, the present application provides a preparation method of an absorbable antibacterial barbed wire, comprising the following steps:

[0103] S1, gel layer wrapping: 3.5 mg / mL fibrinogen and 10 IU / mL thrombin were mixed to obtain a fibrin gel solution; the barbed wire was immersed in the gel solution, and the gel was treated for 40 min, then the barbed wire was pulled out along the barb direction to obtain an intermediate product, the intermediate product was immersed in the acrylic hydrogel prepared in Preparation Example 1 for 20 min to obtain a barbed wire wrapped with a gel layer, and then dried 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%) on the barbed wire wrapped with the gel layer, repeat spraying 3 times, dry, brush antibacterial outer layer solution on the surface of the barbed wire, repeat brushing three times, dry, get antibacterial barbed wire.

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

[0106] Example 7

[0107] In one aspect, the application provides an absorbable antibacterial barbed wire, comprising:

[0108] The barbed wire has same direction or reverse barb structure on the surface;

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

[0110] The antibacterial layer is wrapped outside the gel layer.

[0111] 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] In another aspect, the application provides a preparation method of an absorbable antibacterial barbed wire, comprising the following steps:

[0113] S1, gel layer wrapping: mix 3.5mg / mL fibrinogen with 10IU / mL thrombin to get fibrin gel solution; dip the barbed wire in the gel solution, gelatinize for 40min, pull out the barbed wire along the barb direction to get the intermediate product, dip the intermediate product in the acrylic hydrogel prepared in preparation example 1 for 20min to get the barbed wire wrapped with the gel layer, dry to get the barbed wire wrapped with the gel layer;

[0114] 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, repeat spraying 3 times, dry, brush antibacterial outer layer solution on the surface of the barbed wire, repeat brushing three times, dry, get 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 obtain a 7% (w / v) silk fibroin solution, and the gentamicin solution was mixed with the silk fibroin solution so that the mass ratio of gentamicin to silk fibroin was 1.5:10, thereby obtaining the antibacterial outer layer solution.

[0116] Comparative Example

[0117] Comparative Example 1

[0118] This comparative example differs from Example 1 in that no gel layer was provided in the comparative example, and an antibacterial barbed suture was prepared.

[0119] Comparative Example 2

[0120] This comparative example differs from Example 1 in that no antibacterial layer was provided in the comparative example.

[0121] Comparative Example 3

[0122] This comparative example differs from Example 1 in that no antibacterial inner layer was provided in the comparative example.

[0123] Performance detection test

[0124] (1) Viscosity test: different suture samples were cut to a length of 200 mm, and an Instron material testing machine was used to test the tensile and knot strength of the suture. 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 environment temperature was 20±2°C, and the relative humidity was 65±2%; for the knot strength test, a simple free knot was required for the test sample, the sample was clamped at both ends of the material testing machine, the free knot was located in the middle of the two clamps, and the suture between the clamps was taut, the tensile speed was 300 mm / min, the clamping length was set to 125 mm, the test environment temperature was 20±2°C, and the relative humidity was 65±2%.

[0125] (2) Antibacterial performance: gram-positive Staphylococcus aureus and gram-negative Escherichia coli were selected as test strains. The evaluation standard was ISO 20645:2004 according to the antibacterial activity. The experimental method was to cut different suture samples to a length of 5 cm, inoculate about 1 mL of bacterial suspension (1 x 108CFU / mL) on an agar plate, and place it in a 37°C incubator for 18-24 h. If the inhibitory concentration is reached, there will be no growth of microorganisms, and a clear antibacterial zone will appear around the circular sample.

[0126] Table 1 Performance detection

[0127]

[0128] Similarly, the barbed wire in Example 1 was tested for cell compatibility (live / dead cell staining test), and within 2 days, the cell proliferation had a growth trend, and the viability had no difference. The barbed wire in Comparative Example 1 was tested for cell compatibility (live / dead cell staining test), and within 2 days, the cell proliferation had a growth trend, and the viability had a certain difference, and compared with the barbed wire in Example 1, the cell viability was poorer.

[0129] It can be found from the performance test comparison in Table 1 that:

[0130] 1. It can be found from the comparison of Example 1 and Comparative Examples 1-2 that the antibacterial effect and mechanical strength of the barbed wire prepared in Example 1 are improved, which indicates that the gel layer in the present application has a structure similar to that of human skin and has good compatibility with the human body, which can reduce the probability of the occurrence of the rejection phenomenon 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 breaking of the barbed wire during suturing. Finally, the antibacterial layer wrapped outside the gel layer can make the barbed wire not easy to be contaminated and carry bacteria during use, and can continuously play an antibacterial effect after suturing, effectively inhibiting the redness and swelling of the wound.

[0131] 2. It can be found from the comparison of Example 2-3 and Example 1 that the mechanical strength of the barbed wire prepared in Example 2-3 is improved, which indicates that in the present application, the acrylic hydrogel or the polypeptide hydrogel is preferably added to the gel layer, and the acrylic hydrogel and the polypeptide hydrogel both have excellent water content and good compatibility with the skin, which can cooperate with the fibrin glue to improve the mechanical strength of the barbed wire, and further reduce the rejection phenomenon between the barbed wire and the skin.

[0132] 3. It can be found from the comparison of Example 4-6 and Example 1 that the antibacterial performance of the barbed wire prepared in Example 4-6 is improved, which indicates that in the present application, berberine, gentamicin, and artemisinin are preferably used as additives and added to the antibacterial outer layer, and the additives all have good antibacterial effect, low toxicity, etc., and can be loaded by the porous structure of silk fibroin, so that the additives can be slowly released from the silk fibroin, thereby making the barbed wire obtain long-acting antibacterial effect.

[0133] 4. It can be found from the comparison of Example 7 and Example 1 that the mechanical strength of the barbed wire prepared in Example 1 is decreased, which indicates that in the present application, glycerol is preferably added to the antibacterial outer layer, and the presence of glycerol can promote the formation of the folding structure in the silk fibroin, improve the loading capacity and loading effect of the silk fibroin on the antibacterial materials such as berberine.

[0134] The embodiments are only illustrative of the present application, and are not intended to limit the present application, and those skilled in the art can make modifications to the embodiments without creative contribution after reading the specification, but as long as the modifications are within the scope of the claims of the present application, they are protected by the patent law.

Claims

1. An absorbable antibacterial barbed suture, characterized in that, include: The barbed line has barbs that are oriented in the same direction or in opposite directions. A gel layer, the gel layer being wrapped around the surface of the barb line; An antibacterial layer, which wraps around the gel layer; The gel layer comprises fibrin gel; The fibrin gel is composed of fibrinogen and thrombin; The gel layer further includes polyacrylic acid hydrogel or polypeptide hydrogel; The antibacterial layer comprises an antibacterial inner layer and an antibacterial outer layer, wherein the antibacterial inner layer comprises any one or more of gallic acid, catechin, ferulic acid, and caffeic acid; The antibacterial outer layer includes silk fibroin; The antibacterial outer layer also includes additives, which include any one or more of berberine, gentamicin, and artemisinin.

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

5.

3. A method for preparing an absorbable antibacterial barbed thread according to any one of claims 1-2, characterized in that, Includes the following steps: S1. Gel layer coating: The barbed wire is immersed in the gel solution and gelled. The barbed wire is then pulled out along the barb direction to obtain a barbed wire coated with a gel layer. S2. Antibacterial layer coating: Apply antibacterial solution to the outside of the barbed line coated with gel layer, repeat coating, and dry to obtain antibacterial barbed line.

4. The absorbable antibacterial barbed suture according to claim 3, characterized in that: The coating is repeated 5-10 times.

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