CN111068100A - Medical silk braided suture line and preparation method thereof - Google Patents
Medical silk braided suture line and preparation method thereof Download PDFInfo
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- CN111068100A CN111068100A CN201911194562.3A CN201911194562A CN111068100A CN 111068100 A CN111068100 A CN 111068100A CN 201911194562 A CN201911194562 A CN 201911194562A CN 111068100 A CN111068100 A CN 111068100A
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Abstract
The invention discloses a medical real silk braided suture line and a preparation method thereof. The medical real silk braided suture line has good mechanical property and degradation property, has antibacterial property, enables the antibacterial property to achieve stable and lasting effect, can effectively promote wound healing, and reduces infection of operation parts.
Description
Technical Field
The invention relates to the technical field of medical sutures, in particular to a medical real silk braided suture and a preparation method thereof.
Background
The natural silk contains 18 kinds of amino acids, and after being sewed into human body, the natural silk can produce many amino acids required by human body under the decomposition action of enzyme and microbe, so that the natural silk is absorbed by human body, is harmless to human body and provides useful nutrients. Compared with the medical suture made of chemical fiber materials with the same thread size, the real silk suture is also very excellent in the aspects of softness, knotting flexibility and the like; meanwhile, the silk suture has good hygroscopicity, can rapidly expand when being infiltrated by blood to fill needle holes, reduces the blood seepage from the needle holes, and has good operation quality; the strength of the silk suture is superior to that of common natural suture such as cotton thread and catgut; therefore, silk suture becomes an indispensable suture material in modern surgical operations, especially in operations such as blood vessel ligation and gastrointestinal tract operations.
The silk suture line is used as a natural protein material and is widely used in surgical operations due to good mechanical property. But because the weaving structure of the suture and the nature of animal protein provide a good growing environment for the growth of bacteria, and meanwhile, the suture of wound tissues can generate capillary action, so that the bacteria are adhered and planted on the surface of the suture, and a biological film which is difficult to cure is formed. Therefore, the preparation of the antibacterial suture line with good antibacterial performance has important clinical significance.
Medical sutures must have the following performance requirements:
(1) has higher strength, is not influenced by body fluid to deform within a certain period of time, and has no great change in mechanical property before wound healing.
(2) The flexibility of the fiber is good, the hooking strength is high, the suture can easily pass through human tissues during the suture, the operation is convenient during the ligation, and the knot holding performance after the knotting is good.
(3) Good biocompatibility and no influence on the healing and growth of wound tissues.
(4) For an absorbent suture, it should be completely absorbed after tissue repair without leaving foreign matter in the human body.
(5) The product has stable and reliable quality, can be stored for a long time, and is easy to disinfect without denaturation.
(6) Has no toxicity, anaphylaxis, electrolysis, pyotoxicity, carcinogenicity and capillarity.
The medical silk suture line becomes one of the suture lines widely used in the society at present due to the characteristics of stability and easy operation. However, the real silk suture line serving as a non-absorbable suture line has no bacteriostatic action on bacteria, viruses and the like, and the gaps of the braided structure and the single fiber gaps inside the silk line provide hidden places for the bacteria, so that the probability of infection of the operation part is increased. In order to endow the silk suture with good antibacterial performance, the contact between bacteria and an operation incision is isolated within a certain range, so that the occurrence probability of operation site infection is reduced. Therefore, the research on the medical real silk suture line with antibacterial performance has important clinical application value.
Disclosure of Invention
The invention aims to solve the technical problem of providing a preparation method of a medical real silk braided suture line with high and durable antibacterial performance, slow release, no toxicity, safety and excellent physical and mechanical properties.
The preparation method of the medical real silk braided suture line comprises the steps of firstly loading lysine polyester hydrogel on the real silk braided suture line, and secondly preparing the antibacterial coating on the real silk braided suture line loaded with the lysine polyester hydrogel.
The process of loading the lysine polyester hydrogel on the real silk braided suture comprises the following steps:
(1) dissolving 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride in MES buffer solution with pH of 5.5-6.5 and concentration of 0.05-0.2 mol/L to obtain solution with concentration of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride of 0.1-0.2 g/mL;
(2) immersing 2-4 g of a real silk braided suture in 30-50 mL of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride solution with the concentration of 0.1-0.2 g/mL under an ice bath condition, and stirring and activating for 24-36 hours to obtain a mixed solution I;
(3) weighing lysine polyester ammonia water gel, dispersing in water to prepare a hydrogel solution with the concentration of 1-3 mg/mL, and filtering by using a needleless filter with the pore diameter of 0.22-0.45 mu m to obtain a mixed solution II;
(4) adding 8-15 mL of mixed solution II into the mixed solution I obtained in the step (2), and stirring for grafting reaction for 12-24 hours under an ice bath condition; and after the reaction is finished, washing with water to remove hydrogel which is not grafted on the surface of the real silk braided suture line, and drying at the temperature of 20-30 ℃ to constant weight to obtain the medical real silk braided suture line.
The preparation process of the lysine polyester ammonia water gel comprises the following steps: dissolving 0.7-1.2 g of p-nitrophenyl adipate and 0.8-1.0 g of lysine dibutylene glycol ester in 2.0-3.0 g of dimethylacetamide, adding a mixed solution consisting of 0.1-0.15 g of triclosan and 0.6-0.8 g of triethylamine, and reacting at 60-80 ℃ for 0.5-1 hour to obtain hydrogel; soaking the hydrogel for 2-4 hours by using acetone, wherein the mass ratio of the acetone to the hydrosol is (10-20): 1, and then washing by using water to remove water-soluble impurities in the hydrogel; slicing the washed hydrogel to prepare a hydrogel slice; dissolving trypsin in a PBS buffer solution to obtain a trypsin solution with the enzyme concentration of 0.1-0.5 mg/mL; and (3) slicing the hydrogel at the temperature of 35-37 ℃ in a solid-to-liquid ratio of 1: (10-20) immersing the solution in a trypsin solution, stirring for 4-7 days, dialyzing the obtained degradation solution by using a dialysis bag with the molecular weight of 8-10 ten thousand, and removing enzyme and inorganic salt in a PBS buffer solution; and (3) carrying out vacuum freeze drying on the obtained dialysate at the temperature of-70 to-50 ℃ for 48 to 72 hours to remove water in the hydrogel, thus obtaining the lysine polyester ammonia water gel.
Furthermore, the mass ratio of the p-nitrophenyl adipate to the lysine dibutylene glycol ester is (0.7-1.1): 1.
The lysine-based polyester ammonia gel is prepared by the polymerization reaction of two monomers which are generated by the reaction of L-lysine hydrochloride and 1, 4-butanediol and the chemical reaction of adipoyl chloride and p-nitrophenol under certain conditions. Compared with the common hydrogel, the hydrogel has the advantages of simpler and more convenient synthesis steps and good biocompatibility. The lysine polyurethane hydrogel can rapidly swell to an equilibrium volume within 24 hours in water and still can keep the shape and the three-dimensional space network structure, and is a functional polymer material integrating water absorption, water retention and slow release. By adjusting the mass ratio of two reaction monomers of p-nitrophenyl adipate and lysine dibutylene glycol, hydrogel systems with different performances can be prepared. Meanwhile, the hydrogel has a biodegradation function, and can be degraded into nano hydrogel with uniform shape and narrow particle size distribution under the degradation action of trypsin.
The method utilizes the characteristics of natural protein materials of the real silk suture line to activate free carboxyl on the surface of the real silk suture line; the characteristic that the surface of the nano hydrogel degraded by the lysine-based polyester ammonia water gel is rich in free amino after the lysine-based polyester ammonia water gel is biodegraded is utilized; the nano hydrogel loaded with the antibacterial agent is grafted on the surface of the natural silk suture by adopting a chemical grafting method, so that the silk suture has an excellent long-acting antibacterial function under the condition of keeping excellent physical and mechanical properties of the silk suture.
In some technical schemes of the invention, the process for preparing the antibacterial coating on the real silk braided suture loaded with the lysine polyester hydrogel comprises the following steps: preparing a curcumin water solution with the curcumin concentration of 3-5 mg/mL; soaking the lysine polyester hydrogel-loaded real silk braided suture line in a curcumin aqueous solution at 50-60 ℃, wherein the solid-to-liquid ratio of the lysine polyester hydrogel-loaded real silk braided suture line to the curcumin aqueous solution is 1 (10-30) (g/mL), washing with water after soaking for 60-100 minutes, and drying at 20-30 ℃ to constant weight to obtain the medical real silk braided suture line.
As a more optimized technical scheme, the antibacterial coating is a composite coating and comprises a long-acting antibacterial inner layer and a functional antibacterial outer layer.
In some technical schemes of the invention, the process for preparing the antibacterial coating on the real silk braided suture loaded with the lysine polyester hydrogel comprises the following steps:
(1) preparing a curcumin water solution with the curcumin concentration of 3-5 mg/mL; soaking the lysine polyester hydrogel-loaded real silk braided suture line in a curcumin aqueous solution at 50-60 ℃, wherein the solid-to-liquid ratio of the lysine polyester hydrogel-loaded real silk braided suture line to the curcumin aqueous solution is 1 (10-30) (g/mL), washing with water after soaking for 60-100 minutes, drying at 20-30 ℃ to constant weight, and preparing an antibacterial long-acting inner layer on the surface of the lysine polyester hydrogel-loaded real silk braided suture line;
(2) preparing a curcumin aqueous solution with the curcumin concentration of 3-5 mg/mL and a coating carrier aqueous solution with the coating carrier concentration of 6-9 mg/mL; mixing a curcumin aqueous solution and a coating carrier aqueous solution in a volume ratio of 1 (5-7) to obtain a mixed solution; soaking the real silk braided suture line loaded with the antibacterial long-acting inner layer into the mixed solution at room temperature in a solid-to-liquid ratio of 1 (10-20) (g/mL), and drying at 20-30 ℃ to constant weight after soaking for 40-80 minutes; treating the dried real silk braided suture line with water vapor at the temperature of 50-60 ℃ for 6-10 hours; and drying the real silk braided suture line to constant weight at 20-30 ℃ after treatment to obtain the medical real silk braided suture line simultaneously loaded with the long-acting antibacterial inner layer and the functional antibacterial outer layer.
In some technical schemes of the invention, the process for preparing the antibacterial coating on the real silk braided suture loaded with the lysine polyester hydrogel comprises the following steps:
(1) preparing a curcumin water solution with the curcumin concentration of 3-5 mg/mL; soaking the lysine polyester hydrogel-loaded real silk braided suture line in a curcumin aqueous solution at 50-60 ℃, wherein the solid-to-liquid ratio of the lysine polyester hydrogel-loaded real silk braided suture line to the curcumin aqueous solution is 1 (10-30) (g/mL), washing with water after soaking for 60-100 minutes, drying at 20-30 ℃ to constant weight, and preparing an antibacterial long-acting inner layer on the surface of the lysine polyester hydrogel-loaded real silk braided suture line;
(2) preparing a curcumin aqueous solution with the curcumin concentration of 3-5 mg/mL and a coating carrier aqueous solution with the coating carrier concentration of 6-9 mg/mL; uniformly mixing the coating carrier aqueous solution and glycerol in a mass ratio of (3-4) to 1 to obtain a coating carrier glycerol solution; mixing a curcumin aqueous solution and a coating carrier glycerol solution in a volume ratio of 1 (7-8) to obtain a mixed solution; the silk braided suture line loaded with the long-acting antibacterial inner layer is soaked in the mixed solution at room temperature in a solid-to-liquid ratio of 1 (10-20) (g/mL), and after soaking for 40-60 minutes, the silk braided suture line is dried to constant weight at 50-60 ℃ to obtain the medical silk braided suture line simultaneously loaded with the long-acting antibacterial inner layer and the functional antibacterial outer layer.
Further, the coating carrier is silk fibroin and/or mulberry twig bark cellulose nanowhiskers. Preferably, the coating carrier is a mixture of silk fibroin and mulberry twig bark cellulose nanowhiskers in a mass ratio of 1: 1.
The invention also provides a medical real silk braided suture line which is processed by using any one of the preparation methods of the medical real silk braided suture line.
The medical real silk braided suture line has good mechanical property and degradation property, has antibacterial property, enables the antibacterial property to achieve stable and lasting effect, can effectively promote wound healing, and reduces infection of operation parts.
Detailed Description
The raw materials in the examples are as follows:
MES buffer with pH 5.5 and concentration 0.05mol/L, Beijing Merribo Biotech Co., Ltd.
A silk braided suture, from Jinan Treng commercial Co., Ltd.
Trypsin, Zhengzhou Hongxiang chemical Co., Ltd., enzyme activity 5 ten thousand U/g.
PBS buffer, pH 7.5, 0.05mol/L from Nanjing Senega Biotech Co.
Preparation of p-nitrophenyl adipate: sequentially adding 110g of p-nitrophenol, 71.88g of triethylamine and 450mL of acetone into a reaction device, and stirring and mixing at room temperature; under the conditions of temperature of minus 78 ℃ and stirring, adding 60.405g of adipoyl chloride and 150mL of acetone mixed solution by using a constant-pressure dropping funnel, completing dropping within 1 hour, and fully reacting for 4 hours; after the reaction is complete, the reaction product is washed by water and dried to constant weight in vacuum at 55 ℃ to remove the water contained in the product and obtain the p-nitrophenyl adipate.
Preparation of lysine dibutylene glycol ester: weighing 85.12g of L-lysine hydrochloride and 20g of 1, 4-butanediol, sequentially putting into a reaction device, mixing, adding 3g of p-toluenesulfonic acid monohydrate and 25mL of toluene, and stirring and reacting for 2 hours at 125 ℃; after complete reaction, pouring out toluene, continuously adding 500mL of isopropanol, and stirring at 70 ℃ until the isopropanol is dissolved; after the reaction product is completely dissolved, placing the mixed solution generated by the reaction in an environment with the temperature of-19 ℃ for low-temperature storage for 12 hours, drying in vacuum at the temperature of 55 ℃ to constant weight, and collecting lysine dibutylene glycol ester.
Curcumin, a five-hundred technology ltd, Hebei, manufacturer.
Silk fibroin, a manufacturer, new tencel biotechnology limited, lazhou.
Ramulus mori skin cellulose nanowhiskers, prepared according to example 1 of application No. 201611202906.7, having a diameter of 40nm and a length of 130 nm.
In the case where the present invention is not specifically described, the stirring speed is 100 rpm.
In the case where the present invention is not specifically described, the room temperature is 20 to 25 ℃.
Example 1
The preparation method of the medical real silk braided suture line comprises the steps of firstly loading lysine polyester hydrogel on the real silk braided suture line, and secondly preparing the antibacterial coating on the real silk braided suture line loaded with the lysine polyester hydrogel.
The process of loading the lysine polyester hydrogel on the real silk braided suture comprises the following steps:
(1) dissolving 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) in MES buffer (pH 5.5) at a concentration of 0.05mol/L to obtain a solution of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) at a concentration of 0.1 g/mL;
(2) immersing 3g of a real silk braided suture in 40mL of a solution with the concentration of 0.1g/mL of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) under the ice bath condition, and stirring and activating for 24 hours to obtain a mixed solution I;
(3) weighing lysine polyester ammonia water gel, dispersing in water to prepare a hydrogel solution with the concentration of 2mg/mL, and filtering by using a needleless filter with the pore diameter of 0.45 mu m to obtain a mixed solution II;
(4) adding 10mL of mixed solution II into the mixed solution I obtained in the step (2), and stirring for grafting reaction for 24 hours under the ice bath condition; after the reaction is finished, the hydrogel which is not grafted on the surface of the real silk braided suture is removed by washing with water, and the medical real silk braided suture loaded with the lysine polyester hydrogel is prepared by drying at 30 ℃ to constant weight.
The preparation process of the lysine polyester ammonia water gel comprises the following steps: dissolving 0.76g of p-nitrophenyl adipate and 1.0g of lysine dibutylene glycol ester in 2.0g of dimethylacetamide, adding a mixed solution consisting of 0.12g of triclosan and 0.65g of triethylamine, and reacting at 60 ℃ for 0.5 hour to obtain hydrogel; soaking the hydrogel for 2 hours by using acetone, wherein the mass ratio of the acetone to the hydrosol is 15:1, and then washing by using water to remove water-soluble impurities in the hydrogel; slicing the washed hydrogel to obtain hydrogel slices with length, width and height of 0.5cm × 0.5cm × 0.2 cm; dissolving trypsin in a PBS buffer solution to obtain a trypsin solution with the enzyme concentration of 0.1 mg/mL; at 37 ℃, slicing the hydrogel in a solid-to-liquid ratio of 1: immersing 10g/mL of the mixed solution in a trypsin solution, stirring for 7 days, dialyzing the obtained degradation solution by using a dialysis bag with the molecular weight of 10 ten thousand, and removing enzyme and inorganic salt in a PBS buffer solution; freeze-drying the obtained dialysate at-50 deg.C under 100Pa absolute pressure for 72 hr to remove water in hydrogel, and making into lysine polyester ammonia water gel.
The process for preparing the antibacterial coating on the real silk braided suture loaded with the lysine polyester hydrogel comprises the following steps: preparing a curcumin water solution with the curcumin concentration of 4 mg/mL; soaking the lysine polyester hydrogel-loaded real silk braided suture line in a curcumin aqueous solution at 60 ℃, wherein the solid-to-liquid ratio of the lysine polyester hydrogel-loaded real silk braided suture line to the curcumin aqueous solution is 1:15(g/mL), washing the real silk braided suture line with water 100 times the weight of the real silk braided suture line after soaking for 100 minutes, and drying the real silk braided suture line at 30 ℃ to constant weight to obtain the medical real silk braided suture line.
Example 2
The preparation method of the medical real silk braided suture line comprises the steps of firstly loading lysine polyester hydrogel on the real silk braided suture line, and secondly preparing the antibacterial coating on the real silk braided suture line loaded with the lysine polyester hydrogel.
The process of loading the lysine polyester hydrogel on the real silk braided suture comprises the following steps:
(1) dissolving 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) in MES buffer (pH 5.5) at a concentration of 0.05mol/L to obtain a solution of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) at a concentration of 0.1 g/mL;
(2) immersing 3g of a real silk braided suture in 40mL of a solution with the concentration of 0.1g/mL of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) under the ice bath condition, and stirring and activating for 24 hours to obtain a mixed solution I;
(3) weighing lysine polyester ammonia water gel, dispersing in water to prepare a hydrogel solution with the concentration of 2mg/mL, and filtering by using a needleless filter with the pore diameter of 0.45 mu m to obtain a mixed solution II;
(4) adding 10mL of mixed solution II into the mixed solution I obtained in the step (2), and stirring for grafting reaction for 24 hours under the ice bath condition; after the reaction is finished, the hydrogel which is not grafted on the surface of the real silk braided suture is removed by washing with water, and the medical real silk braided suture loaded with the lysine polyester hydrogel is prepared by drying at 30 ℃ to constant weight.
The preparation process of the lysine polyester ammonia water gel comprises the following steps: dissolving 0.9g of p-nitrophenyl adipate and 1.0g of lysine dibutylene glycol ester in 2.0g of dimethylacetamide, adding a mixed solution consisting of 0.12g of triclosan and 0.65g of triethylamine, and reacting at 60 ℃ for 0.5 hour to obtain hydrogel; soaking the hydrogel for 2 hours by using acetone, wherein the mass ratio of the acetone to the hydrosol is 15:1, and then washing by using water to remove water-soluble impurities in the hydrogel; slicing the washed hydrogel to obtain hydrogel slices with length, width and height of 0.5cm × 0.5cm × 0.2 cm; dissolving trypsin in a PBS buffer solution to obtain a trypsin solution with the enzyme concentration of 0.1 mg/mL; at 37 ℃, slicing the hydrogel in a solid-to-liquid ratio of 1: immersing 10g/mL of the mixed solution in a trypsin solution, stirring for 7 days, dialyzing the obtained degradation solution by using a dialysis bag with the molecular weight of 10 ten thousand, and removing enzyme and inorganic salt in a PBS buffer solution; freeze-drying the obtained dialysate at-50 deg.C under 100Pa absolute pressure for 72 hr to remove water in hydrogel, and making into lysine polyester ammonia water gel.
The process for preparing the antibacterial coating on the real silk braided suture loaded with the lysine polyester hydrogel comprises the following steps: preparing a curcumin water solution with the curcumin concentration of 4 mg/mL; soaking the lysine polyester hydrogel-loaded real silk braided suture line in a curcumin aqueous solution at 60 ℃, wherein the solid-to-liquid ratio of the lysine polyester hydrogel-loaded real silk braided suture line to the curcumin aqueous solution is 1:15(g/mL), washing the real silk braided suture line with water 100 times the weight of the real silk braided suture line after soaking for 100 minutes, and drying the real silk braided suture line at 30 ℃ to constant weight to obtain the medical real silk braided suture line.
Example 3
The preparation method of the medical real silk braided suture line comprises the steps of firstly loading lysine polyester hydrogel on the real silk braided suture line, and secondly preparing the antibacterial coating on the real silk braided suture line loaded with the lysine polyester hydrogel.
The process of loading the lysine polyester hydrogel on the real silk braided suture comprises the following steps:
(1) dissolving 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) in MES buffer (pH 5.5) at a concentration of 0.05mol/L to obtain a solution of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) at a concentration of 0.1 g/mL;
(2) immersing 3g of a real silk braided suture in 40mL of a solution with the concentration of 0.1g/mL of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) under the ice bath condition, and stirring and activating for 24 hours to obtain a mixed solution I;
(3) weighing lysine polyester ammonia water gel, dispersing in water to prepare a hydrogel solution with the concentration of 2mg/mL, and filtering by using a needleless filter with the pore diameter of 0.45 mu m to obtain a mixed solution II;
(4) adding 10mL of mixed solution II into the mixed solution I obtained in the step (2), and stirring for grafting reaction for 24 hours under the ice bath condition; after the reaction is finished, the hydrogel which is not grafted on the surface of the real silk braided suture is removed by washing with water, and the medical real silk braided suture loaded with the lysine polyester hydrogel is prepared by drying at 30 ℃ to constant weight.
The preparation process of the lysine polyester ammonia water gel comprises the following steps: dissolving 1.02g of p-nitrophenyl adipate and 1.0g of lysine dibutylene glycol ester in 2.0g of dimethylacetamide, adding a mixed solution consisting of 0.12g of triclosan and 0.65g of triethylamine, and reacting at 60 ℃ for 0.5 hour to obtain hydrogel; soaking the hydrogel for 2 hours by using acetone, wherein the mass ratio of the acetone to the hydrosol is 15:1, and then washing by using water to remove water-soluble impurities in the hydrogel; slicing the washed hydrogel to obtain hydrogel slices with length, width and height of 0.5cm × 0.5cm × 0.2 cm; dissolving trypsin in a PBS buffer solution to obtain a trypsin solution with the enzyme concentration of 0.1 mg/mL; at 37 ℃, slicing the hydrogel in a solid-to-liquid ratio of 1: immersing 10g/mL of the mixed solution in a trypsin solution, stirring for 7 days, dialyzing the obtained degradation solution by using a dialysis bag with the molecular weight of 10 ten thousand, and removing enzyme and inorganic salt in a PBS buffer solution; freeze-drying the obtained dialysate at-50 deg.C under 100Pa absolute pressure for 72 hr to remove water in hydrogel, and making into lysine polyester ammonia water gel.
The process for preparing the antibacterial coating on the real silk braided suture loaded with the lysine polyester hydrogel comprises the following steps: preparing a curcumin water solution with the curcumin concentration of 4 mg/mL; soaking the lysine polyester hydrogel-loaded real silk braided suture line in a curcumin aqueous solution at 60 ℃, wherein the solid-to-liquid ratio of the lysine polyester hydrogel-loaded real silk braided suture line to the curcumin aqueous solution is 1:15(g/mL), washing the real silk braided suture line with water 100 times the weight of the real silk braided suture line after soaking for 100 minutes, and drying the real silk braided suture line at 30 ℃ to constant weight to obtain the medical real silk braided suture line.
The tensile strength performance of the medical real silk braided suture line is as follows: for experimental reference standard YY0167-2005, YG (B)026G medical textile strength instrument manufactured by Wenzhou Darong textile instruments Limited company is selected as a strength test instrument of real silk suture. Under the conditions of constant temperature and constant humidity, the initial stretching distance of the sample is 125mm, the sample is clamped on a chuck of a stretching instrument, and a suture line between the clamps is tightened, wherein the stretching speed is 300 mm/min. Each sample was tested 4 times and the average was taken.
The specific tests are shown in table 1.
TABLE 1 tensile Strength Performance test
Example 4
The preparation method of the medical real silk braided suture line comprises the steps of firstly loading lysine polyester hydrogel on the real silk braided suture line, and secondly preparing the antibacterial coating on the real silk braided suture line loaded with the lysine polyester hydrogel.
The process of loading the lysine polyester hydrogel on the real silk braided suture comprises the following steps:
(1) dissolving 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) in MES buffer (pH 5.5) at a concentration of 0.05mol/L to obtain a solution of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) at a concentration of 0.1 g/mL;
(2) immersing 3g of a real silk braided suture in 40mL of a solution with the concentration of 0.1g/mL of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) under the ice bath condition, and stirring and activating for 24 hours to obtain a mixed solution I;
(3) weighing lysine polyester ammonia water gel, dispersing in water to prepare a hydrogel solution with the concentration of 2mg/mL, and filtering by using a needleless filter with the pore diameter of 0.45 mu m to obtain a mixed solution II;
(4) adding 10mL of mixed solution II into the mixed solution I obtained in the step (2), and stirring for grafting reaction for 24 hours under the ice bath condition; after the reaction is finished, the hydrogel which is not grafted on the surface of the real silk braided suture is removed by washing with water, and the medical real silk braided suture loaded with the lysine polyester hydrogel is prepared by drying at 30 ℃ to constant weight.
The preparation process of the lysine polyester ammonia gel is the same as that of example 2.
The process for preparing the antibacterial coating on the real silk braided suture loaded with the lysine polyester hydrogel comprises the following steps:
(1) preparing a curcumin water solution with the curcumin concentration of 4 mg/mL; soaking the lysine polyester hydrogel-loaded real silk braided suture line in a curcumin aqueous solution at 60 ℃, wherein the solid-to-liquid ratio of the lysine polyester hydrogel-loaded real silk braided suture line to the curcumin aqueous solution is 1:15(g/mL), washing the real silk braided suture line with water 100 times of the weight of the real silk braided suture line after soaking for 100 minutes, drying the real silk braided suture line to constant weight at 30 ℃, and preparing an antibacterial long-acting inner layer on the surface of the lysine polyester hydrogel-loaded real silk braided suture line;
(2) preparing a curcumin aqueous solution with curcumin concentration of 4mg/mL and a silk fibroin aqueous solution with silk fibroin concentration of 7 mg/mL; mixing a curcumin aqueous solution and a silk fibroin aqueous solution in a volume ratio of 1:6 to obtain a mixed solution; soaking the real silk braided suture line loaded with the antibacterial long-acting inner layer in a solid-to-liquid ratio of 1:10(g/mL) in the mixed solution at room temperature for 60 minutes, and drying at 30 ℃ to constant weight; treating the dried real silk braided suture line with water vapor at 60 ℃ for 6 hours; and drying the real silk braided suture line at 30 ℃ to constant weight after treatment to obtain the medical real silk braided suture line simultaneously loaded with the long-acting antibacterial inner layer and the functional antibacterial outer layer.
Example 5
The preparation method of the medical real silk braided suture line comprises the steps of firstly loading lysine polyester hydrogel on the real silk braided suture line, and secondly preparing the antibacterial coating on the real silk braided suture line loaded with the lysine polyester hydrogel.
The process of loading the lysine polyester hydrogel on the real silk braided suture comprises the following steps:
(1) dissolving 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) in MES buffer (pH 5.5) at a concentration of 0.05mol/L to obtain a solution of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) at a concentration of 0.1 g/mL;
(2) immersing 3g of a real silk braided suture in 40mL of a solution with the concentration of 0.1g/mL of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) under the ice bath condition, and stirring and activating for 24 hours to obtain a mixed solution I;
(3) weighing lysine polyester ammonia water gel, dispersing in water to prepare a hydrogel solution with the concentration of 2mg/mL, and filtering by using a needleless filter with the pore diameter of 0.45 mu m to obtain a mixed solution II;
(4) adding 10mL of mixed solution II into the mixed solution I obtained in the step (2), and stirring for grafting reaction for 24 hours under the ice bath condition; after the reaction is finished, the hydrogel which is not grafted on the surface of the real silk braided suture is removed by washing with water, and the medical real silk braided suture loaded with the lysine polyester hydrogel is prepared by drying at 30 ℃ to constant weight.
The preparation process of the lysine polyester ammonia gel is the same as that of example 2.
The process for preparing the antibacterial coating on the real silk braided suture loaded with the lysine polyester hydrogel comprises the following steps:
(1) preparing a curcumin water solution with the curcumin concentration of 4 mg/mL; soaking the lysine polyester hydrogel-loaded real silk braided suture line in a curcumin aqueous solution at 60 ℃, wherein the solid-to-liquid ratio of the lysine polyester hydrogel-loaded real silk braided suture line to the curcumin aqueous solution is 1:15(g/mL), washing the real silk braided suture line with water 100 times of the weight of the real silk braided suture line after soaking for 100 minutes, drying the real silk braided suture line to constant weight at 30 ℃, and preparing an antibacterial long-acting inner layer on the surface of the lysine polyester hydrogel-loaded real silk braided suture line;
(2) preparing a curcumin aqueous solution with curcumin concentration of 4mg/mL and a silk fibroin aqueous solution with silk fibroin concentration of 7 mg/mL; uniformly mixing silk fibroin aqueous solution and glycerol in a mass ratio of 3:1 to obtain silk fibroin glycerol solution; mixing a curcumin aqueous solution and a silk fibroin glycerol solution in a volume ratio of 1:8 to obtain a mixed solution; and (3) soaking the silk braided suture line loaded with the long-acting antibacterial inner layer in a solid-to-liquid ratio of 1:10(g/mL) in the mixed solution at room temperature for 60 minutes, and drying at 60 ℃ to constant weight to obtain the medical silk braided suture line simultaneously loaded with the long-acting antibacterial inner layer and the functional antibacterial outer layer.
Comparative example 1
The preparation method of the medical real silk braided suture line comprises the steps of firstly loading lysine polyester hydrogel on the real silk braided suture line, and secondly preparing the antibacterial coating on the real silk braided suture line loaded with the lysine polyester hydrogel.
The process of loading the lysine polyester hydrogel on the real silk braided suture comprises the following steps:
(1) dissolving 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) in MES buffer (pH 5.5) at a concentration of 0.05mol/L to obtain a solution of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) at a concentration of 0.1 g/mL;
(2) immersing 3g of a real silk braided suture in 40mL of a solution with the concentration of 0.1g/mL of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) under the ice bath condition, and stirring and activating for 24 hours to obtain a mixed solution I;
(3) weighing lysine polyester ammonia water gel, dispersing in water to prepare a hydrogel solution with the concentration of 2mg/mL, and filtering by using a needleless filter with the pore diameter of 0.45 mu m to obtain a mixed solution II;
(4) adding 10mL of mixed solution II into the mixed solution I obtained in the step (2), and stirring for grafting reaction for 24 hours under the ice bath condition; after the reaction is finished, the hydrogel which is not grafted on the surface of the real silk braided suture is removed by washing with water, and the medical real silk braided suture loaded with the lysine polyester hydrogel is prepared by drying at 30 ℃ to constant weight.
The preparation process of the lysine polyester ammonia gel is the same as that of example 2.
The process for preparing the antibacterial coating on the real silk braided suture loaded with the lysine polyester hydrogel comprises the following steps: preparing a curcumin aqueous solution with curcumin concentration of 4mg/mL and a silk fibroin aqueous solution with silk fibroin concentration of 7 mg/mL; mixing a curcumin aqueous solution and a silk fibroin aqueous solution in a volume ratio of 1:6 to obtain a mixed solution; soaking the real silk braided suture line loaded with the antibacterial long-acting inner layer in a solid-to-liquid ratio of 1:10(g/mL) in the mixed solution at room temperature for 60 minutes, and drying at 30 ℃ to constant weight; treating the dried real silk braided suture line with water vapor at 60 ℃ for 6 hours; and drying the real silk braided suture line at 30 ℃ to constant weight after treatment to obtain the medical real silk braided suture line.
Comparative example 2
The preparation method of the medical real silk braided suture line comprises the steps of firstly loading lysine polyester hydrogel on the real silk braided suture line, and secondly preparing the antibacterial coating on the real silk braided suture line loaded with the lysine polyester hydrogel.
The process of loading the lysine polyester hydrogel on the real silk braided suture comprises the following steps:
(1) dissolving 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) in MES buffer (pH 5.5) at a concentration of 0.05mol/L to obtain a solution of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) at a concentration of 0.1 g/mL;
(2) immersing 3g of a real silk braided suture in 40mL of a solution with the concentration of 0.1g/mL of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) under the ice bath condition, and stirring and activating for 24 hours to obtain a mixed solution I;
(3) weighing lysine polyester ammonia water gel, dispersing in water to prepare a hydrogel solution with the concentration of 2mg/mL, and filtering by using a needleless filter with the pore diameter of 0.45 mu m to obtain a mixed solution II;
(4) adding 10mL of mixed solution II into the mixed solution I obtained in the step (2), and stirring for grafting reaction for 24 hours under the ice bath condition; after the reaction is finished, the hydrogel which is not grafted on the surface of the real silk braided suture is removed by washing with water, and the medical real silk braided suture loaded with the lysine polyester hydrogel is prepared by drying at 30 ℃ to constant weight.
The preparation process of the lysine polyester ammonia gel is the same as that of example 2.
The process for preparing the antibacterial coating on the real silk braided suture loaded with the lysine polyester hydrogel comprises the following steps: preparing a curcumin aqueous solution with curcumin concentration of 4mg/mL and a silk fibroin aqueous solution with silk fibroin concentration of 7 mg/mL; uniformly mixing silk fibroin aqueous solution and glycerol in a mass ratio of 3:1 to obtain silk fibroin glycerol solution; mixing a curcumin aqueous solution and a silk fibroin glycerol solution in a volume ratio of 1:8 to obtain a mixed solution; and (3) soaking the real silk braided suture line loaded with the antibacterial long-acting inner layer in a solid-to-liquid ratio of 1:10(g/mL) in the mixed solution at room temperature for 60 minutes, and drying at 60 ℃ to constant weight to obtain the medical real silk braided suture line.
Example 6
The preparation method of the medical real silk braided suture line comprises the steps of firstly loading lysine polyester hydrogel on the real silk braided suture line, and secondly preparing the antibacterial coating on the real silk braided suture line loaded with the lysine polyester hydrogel.
The process of loading the lysine polyester hydrogel on the real silk braided suture comprises the following steps:
(1) dissolving 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) in MES buffer (pH 5.5) at a concentration of 0.05mol/L to obtain a solution of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) at a concentration of 0.1 g/mL;
(2) immersing 3g of a real silk braided suture in 40mL of a solution with the concentration of 0.1g/mL of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) under the ice bath condition, and stirring and activating for 24 hours to obtain a mixed solution I;
(3) weighing lysine polyester ammonia water gel, dispersing in water to prepare a hydrogel solution with the concentration of 2mg/mL, and filtering by using a needleless filter with the pore diameter of 0.45 mu m to obtain a mixed solution II;
(4) adding 10mL of mixed solution II into the mixed solution I obtained in the step (2), and stirring for grafting reaction for 24 hours under the ice bath condition; after the reaction is finished, the hydrogel which is not grafted on the surface of the real silk braided suture is removed by washing with water, and the medical real silk braided suture loaded with the lysine polyester hydrogel is prepared by drying at 30 ℃ to constant weight.
The preparation process of the lysine polyester ammonia gel is the same as that of example 2.
The process for preparing the antibacterial coating on the real silk braided suture loaded with the lysine polyester hydrogel comprises the following steps:
(1) preparing a curcumin water solution with the curcumin concentration of 4 mg/mL; soaking the lysine polyester hydrogel-loaded real silk braided suture line in a curcumin aqueous solution at 60 ℃, wherein the solid-to-liquid ratio of the lysine polyester hydrogel-loaded real silk braided suture line to the curcumin aqueous solution is 1:15(g/mL), washing the real silk braided suture line with water 100 times of the weight of the real silk braided suture line after soaking for 100 minutes, drying the real silk braided suture line to constant weight at 30 ℃, and preparing an antibacterial long-acting inner layer on the surface of the lysine polyester hydrogel-loaded real silk braided suture line;
(2) preparing a curcumin aqueous solution with curcumin concentration of 4mg/mL and a mulberry twig bark cellulose nanowhisker aqueous solution with mulberry twig bark cellulose nanowhisker concentration of 7 mg/mL; mixing a curcumin aqueous solution and a mulberry twig bark cellulose nanowhisker aqueous solution in a volume ratio of 1:6 to obtain a mixed solution; soaking the real silk braided suture line loaded with the antibacterial long-acting inner layer in a solid-to-liquid ratio of 1:10(g/mL) in the mixed solution at room temperature for 60 minutes, and drying at 30 ℃ to constant weight; treating the dried real silk braided suture line with water vapor at 60 ℃ for 6 hours; and drying the real silk braided suture line at 30 ℃ to constant weight after treatment to obtain the medical real silk braided suture line simultaneously loaded with the long-acting antibacterial inner layer and the functional antibacterial outer layer.
Example 7
The preparation method of the medical real silk braided suture line comprises the steps of firstly loading lysine polyester hydrogel on the real silk braided suture line, and secondly preparing the antibacterial coating on the real silk braided suture line loaded with the lysine polyester hydrogel.
The process of loading the lysine polyester hydrogel on the real silk braided suture comprises the following steps:
(1) dissolving 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) in MES buffer (pH 5.5) at a concentration of 0.05mol/L to obtain a solution of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) at a concentration of 0.1 g/mL;
(2) immersing 3g of a real silk braided suture in 40mL of a solution with the concentration of 0.1g/mL of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) under the ice bath condition, and stirring and activating for 24 hours to obtain a mixed solution I;
(3) weighing lysine polyester ammonia water gel, dispersing in water to prepare a hydrogel solution with the concentration of 2mg/mL, and filtering by using a needleless filter with the pore diameter of 0.45 mu m to obtain a mixed solution II;
(4) adding 10mL of mixed solution II into the mixed solution I obtained in the step (2), and stirring for grafting reaction for 24 hours under the ice bath condition; after the reaction is finished, the hydrogel which is not grafted on the surface of the real silk braided suture is removed by washing with water, and the medical real silk braided suture loaded with the lysine polyester hydrogel is prepared by drying at 30 ℃ to constant weight.
The preparation process of the lysine polyester ammonia gel is the same as that of example 2.
The process for preparing the antibacterial coating on the real silk braided suture loaded with the lysine polyester hydrogel comprises the following steps:
(1) preparing a curcumin water solution with the curcumin concentration of 4 mg/mL; soaking the lysine polyester hydrogel-loaded real silk braided suture line in a curcumin aqueous solution at 60 ℃, wherein the solid-to-liquid ratio of the lysine polyester hydrogel-loaded real silk braided suture line to the curcumin aqueous solution is 1:15(g/mL), washing the real silk braided suture line with water 100 times of the weight of the real silk braided suture line after soaking for 100 minutes, drying the real silk braided suture line to constant weight at 30 ℃, and preparing an antibacterial long-acting inner layer on the surface of the lysine polyester hydrogel-loaded real silk braided suture line;
(2) preparing a curcumin aqueous solution with curcumin concentration of 4mg/mL and a coating carrier aqueous solution with coating carrier concentration of 7 mg/mL; mixing a curcumin aqueous solution and a coating carrier aqueous solution in a volume ratio of 1:6 to obtain a mixed solution; soaking the real silk braided suture line loaded with the antibacterial long-acting inner layer in a solid-to-liquid ratio of 1:10(g/mL) in the mixed solution at room temperature for 60 minutes, and drying at 30 ℃ to constant weight; treating the dried real silk braided suture line with water vapor at 60 ℃ for 6 hours; and drying the real silk braided suture line at 30 ℃ to constant weight after treatment to obtain the medical real silk braided suture line simultaneously loaded with the long-acting antibacterial inner layer and the functional antibacterial outer layer.
The coating carrier is a mixture of silk fibroin and mulberry twig bark cellulose nanowhiskers in a mass ratio of 1: 1.
Test example 1
The mechanical performance of the medical silk braided suture line is tested as follows:
and (3) testing knotting strength and tensile property: the suture samples were cut to 200mm length and tested for tensile and knot strength using an Instron materials tester.
And (3) tensile strength test: the sample is clamped at two ends of a material testing machine, the stretching speed is 300mm/min, the clamping length is set to be 125mm, the testing environment temperature is 20 +/-2 ℃, and the relative humidity is 65 +/-2%.
And (3) testing knotting strength: a simple free knot needs to be tied on a test sample, the sample is clamped at two ends of a material testing machine, the free knot is positioned between two chucks, a suture line between the chucks is tightened, the stretching speed is 300mm/min, the clamping length is set to be 125mm, the test environment temperature is 20 +/-2 ℃, and the relative humidity is 65 +/-2%.
And (3) bending testing: the bending rigidity of the suture is measured by adopting a cantilever beam method, a coating suture sample of 5cm is accurately sheared, one end of the coating suture is fixed on a plane by using an adhesive tape, the fixed length of the extending plane is 1cm, a certain force F is applied to the end point of the suture, the deflection F of the head end of the suture is measured, the bending degree of the suture is calculated by a formula, and five parallel samples are arranged in each sample.
B＝F×L3/3f×100
Wherein F is the external force at the end of the suture; l-the fixed length of suture extension; f-the flexibility of the suture head end.
The specific test results are shown in table 2.
TABLE 2 mechanical Property test Table
The results show that the knotting strength, the tensile strength and the bending rigidity of the medical silk braided suture line loaded with the long-acting antibacterial inner layer and the functional antibacterial outer layer are improved, and the coating strengthens the bonding and cohesion capacity between fibers, so that the physical and mechanical properties of the suture line are improved.
Test example 2
The antibacterial performance test of the medical real silk braided suture line:
gram-positive staphylococcus aureus and gram-negative escherichia coli were selected as test species. Evaluation according to antibacterial activity, evaluation standard ISO 20645: 2004. the experimental procedure was to cut samples of different sutures to 5cm in length and inoculate the samples with approximately 1mL of bacterial suspension (1X 10)8CFU/mL) in agar plates, and placing the plates in an incubator at 37 ℃ for 18-24h, if the inhibitory concentration is reached, no microorganism will grow, and an obvious bacteriostatic area appears around the round sample. At least 3 measurements were made for each sample, and the average was taken as the test result.
Calculation formula of the inhibition zone: h ═ D/2
In the formula: h-the width of the zone of inhibition in millimeters (mm); d is the average of the outer diameter of the zone in millimeters (mm); d is the sample diameter in millimeters (mm).
The specific test results are shown in table 3.
TABLE 3 antibacterial Property test Table
Test example 3
Testing the in-vitro degradation performance of the medical real silk braided suture: the experimental sample is a medical silk braided suture, a high-temperature sterilized glass bottle is used, a buffer solution prepared from disodium hydrogen phosphate and potassium dihydrogen phosphate is used as a simulated body fluid (the pH value is 7.3, and is close to the pH value of an electrolyte solution in a human body), degradation is carried out under the condition of an incubator at 37 ℃, sampling tests are carried out by taking 0 day, 7 days, 21 days and 42 days as time points, and knotting strength in the degradation process of the suture is mainly analyzed.
Wherein the measure of the knotting strength is the strength retention rate, and the strength of the suture before soaking is F0(N), suture strength after soaking F1(N), calculating the strength change in the degradation process according to the formula: strength retention (%) ═ F1/F0×100。
The specific test results are shown in table 4.
TABLE 4 degradation Property test Table
It should be understood that although the present description refers to embodiments, not every embodiment may contain only a single embodiment, and such description is for clarity only, and those skilled in the art will be able to make the description as a whole, and the embodiments may be appropriately combined to form other embodiments as will be appreciated by those skilled in the art.
Claims (10)
1. The preparation method of the medical real silk braided suture line is characterized in that lysine polyester hydrogel is loaded on the real silk braided suture line firstly, and then the antibacterial coating is prepared on the real silk braided suture line loaded with the lysine polyester hydrogel.
2. The method for preparing the medical silk braided suture line according to claim 1, wherein the process of loading the lysine polyester hydrogel on the silk braided suture line comprises the following steps:
(1) dissolving 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride in MES buffer solution with pH of 5.5-6.5 and concentration of 0.05-0.2 mol/L to obtain solution with concentration of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride of 0.1-0.2 g/mL;
(2) immersing 2-4 g of a real silk braided suture in 30-50 mL of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride solution with the concentration of 0.1-0.2 g/mL under an ice bath condition, and stirring and activating for 24-36 hours to obtain a mixed solution I;
(3) weighing lysine polyester ammonia water gel, dispersing in water to prepare a hydrogel solution with the concentration of 1-3 mg/mL, and filtering by using a needleless filter with the pore diameter of 0.22-0.45 mu m to obtain a mixed solution II;
(4) adding 8-15 mL of mixed solution II into the mixed solution I obtained in the step (2), and stirring for grafting reaction for 12-24 hours under an ice bath condition; and after the reaction is finished, washing with water to remove hydrogel which is not grafted on the surface of the real silk braided suture, and drying at the temperature of 20-30 ℃ to constant weight to obtain the medical real silk braided suture loaded with the lysine polyester hydrogel.
3. The method for preparing a medical silk braided suture line according to claim 2, wherein the lysine polyester ammonia water gel is prepared by the following steps: dissolving 0.7-1.2 g of p-nitrophenyl adipate and 0.8-1.0 g of lysine dibutylene glycol ester in 2.0-3.0 g of dimethylacetamide, adding a mixed solution consisting of 0.1-0.15 g of triclosan and 0.6-0.8 g of triethylamine, and reacting at 60-80 ℃ for 0.5-1 hour to obtain hydrogel; soaking the hydrogel for 2-4 hours by using acetone, wherein the mass ratio of the acetone to the hydrosol is (10-20): 1, and then washing by using water to remove water-soluble impurities in the hydrogel; slicing the washed hydrogel to prepare a hydrogel slice; dissolving trypsin in a PBS buffer solution to obtain a trypsin solution with the enzyme concentration of 0.1-0.5 mg/mL; and (3) slicing the hydrogel at the temperature of 35-37 ℃ in a solid-to-liquid ratio of 1: (10-20) immersing the solution in a trypsin solution, stirring for 4-7 days, dialyzing the obtained degradation solution by using a dialysis bag with the molecular weight of 8-10 ten thousand, and removing enzyme and inorganic salt in a PBS buffer solution; and (3) carrying out vacuum freeze drying on the obtained dialysate at the temperature of-70 to-50 ℃ for 48 to 72 hours to remove water in the hydrogel, thus obtaining the lysine polyester ammonia water gel.
4. The preparation method of the medical silk braided suture line according to claim 3, wherein the mass ratio of the p-nitrophenyl adipate to the lysine dibutylene glycol ester is (0.7-1.1): 1.
5. The method for preparing the medical silk braided suture line according to claim 1, wherein the process for preparing the antibacterial coating on the silk braided suture line loaded with the lysine polyester hydrogel comprises the following steps: preparing a curcumin water solution with the curcumin concentration of 3-5 mg/mL; soaking the lysine polyester hydrogel-loaded real silk braided suture line in a curcumin aqueous solution at 50-60 ℃, wherein the solid-to-liquid ratio of the lysine polyester hydrogel-loaded real silk braided suture line to the curcumin aqueous solution is 1 (10-30) (g/mL), washing with water after soaking for 60-100 minutes, and drying at 20-30 ℃ to constant weight to obtain the medical real silk braided suture line.
6. The method for preparing a medical silk braided suture line according to claim 1, wherein the antibacterial coating is a composite coating and comprises a long-acting antibacterial inner layer and a functional antibacterial outer layer.
7. The method for preparing the medical silk braided suture line according to claim 1, wherein the process for preparing the antibacterial coating on the silk braided suture line loaded with the lysine polyester hydrogel comprises the following steps:
(1) preparing a curcumin water solution with the curcumin concentration of 3-5 mg/mL; soaking the lysine polyester hydrogel-loaded real silk braided suture line in a curcumin aqueous solution at 50-60 ℃, wherein the solid-to-liquid ratio of the lysine polyester hydrogel-loaded real silk braided suture line to the curcumin aqueous solution is 1 (10-30) (g/mL), washing with water after soaking for 60-100 minutes, drying at 20-30 ℃ to constant weight, and preparing an antibacterial long-acting inner layer on the surface of the lysine polyester hydrogel-loaded real silk braided suture line;
(2) preparing a curcumin aqueous solution with the curcumin concentration of 3-5 mg/mL and a coating carrier aqueous solution with the coating carrier concentration of 6-9 mg/mL; mixing a curcumin aqueous solution and a coating carrier aqueous solution in a volume ratio of 1 (5-7) to obtain a mixed solution; soaking the real silk braided suture line loaded with the antibacterial long-acting inner layer into the mixed solution at room temperature in a solid-to-liquid ratio of 1 (10-20) (g/mL), and drying at 20-30 ℃ to constant weight after soaking for 40-80 minutes; treating the dried real silk braided suture line with water vapor at the temperature of 50-60 ℃ for 6-10 hours; and drying the real silk braided suture line to constant weight at 20-30 ℃ after treatment to obtain the medical real silk braided suture line simultaneously loaded with the long-acting antibacterial inner layer and the functional antibacterial outer layer.
8. The method for preparing the medical silk braided suture line according to claim 1, wherein the process for preparing the antibacterial coating on the silk braided suture line loaded with the lysine polyester hydrogel comprises the following steps:
(1) preparing a curcumin water solution with the curcumin concentration of 3-5 mg/mL; soaking the lysine polyester hydrogel-loaded real silk braided suture line in a curcumin aqueous solution at 50-60 ℃, wherein the solid-to-liquid ratio of the lysine polyester hydrogel-loaded real silk braided suture line to the curcumin aqueous solution is 1 (10-30) (g/mL), washing with water after soaking for 60-100 minutes, drying at 20-30 ℃ to constant weight, and preparing an antibacterial long-acting inner layer on the surface of the lysine polyester hydrogel-loaded real silk braided suture line;
(2) preparing a curcumin aqueous solution with the curcumin concentration of 3-5 mg/mL and a coating carrier aqueous solution with the coating carrier concentration of 6-9 mg/mL; uniformly mixing the coating carrier aqueous solution and glycerol in a mass ratio of (3-4) to 1 to obtain a coating carrier glycerol solution; mixing a curcumin aqueous solution and a coating carrier glycerol solution in a volume ratio of 1 (7-8) to obtain a mixed solution; the silk braided suture line loaded with the long-acting antibacterial inner layer is soaked in the mixed solution at room temperature in a solid-to-liquid ratio of 1 (10-20) (g/mL), and after soaking for 40-60 minutes, the silk braided suture line is dried to constant weight at 50-60 ℃ to obtain the medical silk braided suture line simultaneously loaded with the long-acting antibacterial inner layer and the functional antibacterial outer layer.
9. The method for preparing a medical silk braided suture line according to claim 7 or 8, wherein the coating carrier is silk fibroin and/or ramulus mori skin cellulose nanowhiskers.
10. The medical real silk braided suture line is characterized by being processed by the preparation method of the medical real silk braided suture line according to any one of claims 1 to 9.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113046884A (en) * | 2021-03-25 | 2021-06-29 | 台州市中心医院（台州学院附属医院） | Antibacterial degradable medical suture |
| CN113730644A (en) * | 2021-09-13 | 2021-12-03 | 苏州大学 | Suture line with gel coating and preparation method thereof |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104857556A (en) * | 2015-05-15 | 2015-08-26 | 东华大学 | Chemical grafted type long-acting sustained-release silk suture with antibacterial function and preparation method of silk suture |
| CN107599544A (en) * | 2017-09-13 | 2018-01-19 | 江苏科技大学 | Ramulus Mori fiber fibroin albumen multilayer complex films and preparation method thereof |
| CN107897205A (en) * | 2017-11-16 | 2018-04-13 | 重庆市畜牧科学院 | Modified ramulus mori bastuse nano silver Synergistic antimicrobial material and preparation method thereof |
| CN108853563A (en) * | 2018-06-26 | 2018-11-23 | 常州市蒽盗钟情生物科技有限公司 | A kind of preparation method of absorbable suture |
| CN108904869A (en) * | 2018-07-20 | 2018-11-30 | 南通纺织丝绸产业技术研究院 | A kind of suture and preparation method thereof with natural antibacterial drug slow release function |
| CN110124091A (en) * | 2019-05-27 | 2019-08-16 | 南通大学附属医院 | Suture and preparation method thereof |
| CN209286263U (en) * | 2018-05-14 | 2019-08-23 | 淮安市晨光医疗器械有限公司 | A kind of absorbable suture |
| CN110327493A (en) * | 2019-08-07 | 2019-10-15 | 重庆市畜牧科学院 | A kind of compound bio bracket and preparation method |
-
2019
- 2019-11-28 CN CN201911194562.3A patent/CN111068100B/en active Active
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104857556A (en) * | 2015-05-15 | 2015-08-26 | 东华大学 | Chemical grafted type long-acting sustained-release silk suture with antibacterial function and preparation method of silk suture |
| CN107599544A (en) * | 2017-09-13 | 2018-01-19 | 江苏科技大学 | Ramulus Mori fiber fibroin albumen multilayer complex films and preparation method thereof |
| CN107897205A (en) * | 2017-11-16 | 2018-04-13 | 重庆市畜牧科学院 | Modified ramulus mori bastuse nano silver Synergistic antimicrobial material and preparation method thereof |
| CN209286263U (en) * | 2018-05-14 | 2019-08-23 | 淮安市晨光医疗器械有限公司 | A kind of absorbable suture |
| CN108853563A (en) * | 2018-06-26 | 2018-11-23 | 常州市蒽盗钟情生物科技有限公司 | A kind of preparation method of absorbable suture |
| CN108904869A (en) * | 2018-07-20 | 2018-11-30 | 南通纺织丝绸产业技术研究院 | A kind of suture and preparation method thereof with natural antibacterial drug slow release function |
| CN110124091A (en) * | 2019-05-27 | 2019-08-16 | 南通大学附属医院 | Suture and preparation method thereof |
| CN110327493A (en) * | 2019-08-07 | 2019-10-15 | 重庆市畜牧科学院 | A kind of compound bio bracket and preparation method |
Non-Patent Citations (5)
| Title |
|---|
| 何小维: "《医药用碳水化合物》", 31 January 2016, 中国轻工业出版社 * |
| 刘琳: "用桑枝皮提取果胶及制备的纳米纤维素晶须在丝素复合膜中的应用", 《蚕业科学》 * |
| 尉霞: "《产业用纺织品设计与生产》", 31 August 2009, 上海：东华大学出版社 * |
| 徐孝旭: "《无机纳粹粒子 柞蚕丝素复合膜的制备、结构及性能研究》", 31 December 2012, 辽宁科学出版社 * |
| 贺超恒: "丝素蛋白载药抗菌医用缝合线的制备和性能研究", 《中国优秀硕士学位论文全文数据库 医药卫生科技辑》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113046884A (en) * | 2021-03-25 | 2021-06-29 | 台州市中心医院（台州学院附属医院） | Antibacterial degradable medical suture |
| CN113730644A (en) * | 2021-09-13 | 2021-12-03 | 苏州大学 | Suture line with gel coating and preparation method thereof |
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