CN111840630A - Bacteriostatic absorbable medical soft tissue suture line and preparation method and application thereof - Google Patents
Bacteriostatic absorbable medical soft tissue suture line and preparation method and application thereof Download PDFInfo
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Abstract
The invention discloses a bacteriostatic absorbable medical soft tissue suture line and a preparation method and application thereof. According to the invention, carboxymethyl chitosan is used as a main carrier, carbon-supported copper and low-molecular-weight aldehyde chitosan are used as chelating agents to prepare chitosan copper-based hydrogel, and the chitosan copper-based hydrogel is mechanically stretched or injected by an injector to prepare the bacteriostatic absorbable medical soft tissue suture line with the diameter of 0.01-3 mm. The invention provides a method for preparing a soft tissue suture from a hyper-stretched hydrogel for the first time, the suture has good mechanical property, high biocompatibility and antibacterial property of a conventional suture, and also has excellent water-absorbing swelling property, and can reduce the occurrence of inflammatory reaction, the formation of scar tissue, tissue tearing and secondary damage to a patient caused by suture removal.
Description
Technical Field
The invention belongs to the technical field of medical sutures, and particularly relates to a bacteriostatic absorbable medical soft tissue suture as well as a preparation method and application thereof.
Background
In recent years, attention has been paid to repair of soft tissue injuries such as liver, kidney, ovary, and lung. The traditional clinical treatment method is dressing such as suture or biological adhesive. Depending on the length of time the suture is degraded in vivo, it can be divided into absorbable and non-absorbable sutures. The absorbable suture is easy to degrade in vivo, and has the defects of poor mechanical property, easy inflammation and easy slipping of knots. The appearance of synthetic non-absorbable suture greatly improves the mechanical property of the suture and solves the problem that suture knots are easy to fall off, but the rigid mechanical property and the weaker stretching deformation capability of the suture easily cause tissue tearing. In addition, regenerated tissue grows along the suture, creating severe scar tissue. Some wound dressings are also used for repairing soft tissues in the recent years, but no external stent or suture material is used for fixing the tissues, and the problem of insufficient mechanical strength of the wound dressings commonly exists. Moreover, most wound dressings are hydrogel materials, and are difficult to store and store due to water loss, so that the wound dressings are not suitable for large-scale application.
Therefore, the development of a new material for repairing soft tissue injury, which integrates the advantages of biological suture and wound dressing, is urgent.
Disclosure of Invention
In order to overcome the defects and shortcomings in the prior art, the invention aims to provide a preparation method of a bacteriostatic absorbable medical soft tissue suture. Carboxymethyl chitosan is used as a main carrier, and carbon-supported copper and low-molecular-weight aldehyde chitosan are used as chelating agents to prepare the absorbable soft tissue suture line with antibacterial property.
The invention also aims to provide the bacteriostatic absorbable medical soft tissue suture prepared by the method.
The invention further aims to provide application of the bacteriostatic absorbable medical soft tissue suture line in preparation of medicines.
The purpose of the invention is realized by the following technical scheme:
a preparation method of a bacteriostatic absorbable medical soft tissue suture comprises the following steps:
(1) sequentially adding p-aldehyde benzoic acid, 4-Dimethylaminopyridine (DMAP) and Dicyclohexylcarbodiimide (DCC) into a chitosan solution at room temperature under the protection of nitrogen or inert gas, reacting, purifying, drying and dialyzing to obtain aldehyde chitosan;
(2) Dispersing the aldehyde chitosan into water, then adding the dispersed aldehyde chitosan into a carboxymethyl chitosan solution, and uniformly mixing to obtain a carboxymethyl chitosan-aldehyde chitosan mixed solution;
(3) adding the carbon-loaded copper suspension into the carboxymethyl chitosan-aldehyde chitosan mixed solution under the stirring state, continuously stirring in a dark place, standing in a dark place to form a gel state, solidifying to obtain chitosan copper-based hydrogel, and preparing the chitosan copper-based hydrogel into a copper hydrogel wire material with the diameter of 0.05-3 mm to obtain the antibacterial absorbable medical soft tissue suture;
in the step (3), the mass ratio of the carboxymethyl chitosan, the aldehyde chitosan and the carbon-supported copper is (20-1120): (5-187): (2-16); more preferably 187 to 1120: 93-187: 2 to 6.
Preferably, the mass ratio of the p-aldehyde benzoic acid, the 4-Dimethylaminopyridine (DMAP), the Dicyclohexylcarbodiimide (DCC) and the chitosan in the step (1) is (450.39-900.75): (1.22-12.2): (0.21-20.6): 1000, parts by weight; more preferably 600: 4: 2: 1000.
preferably, in the chitosan solution in the step (1), the ratio of chitosan to solvent is (0.6-9.6) g: (5-100) ml.
Preferably, in the chitosan solution in the step (1), the molecular weight of the chitosan is 800-5000.
Preferably, the reaction temperature in the step (1) is room temperature, and the reaction time is 10-24 h.
Preferably, the purification in step (1) is to add water to the reaction product of step (1) to precipitate the product, filter, and then wash with water several times.
Preferably, the drying in step (1) is a drying operation conventional in the art.
Preferably, the dialysis in step (1) refers to dialyzing the reaction product in water for 3 days by using a dialysis bag with molecular weight of 1000 to obtain the aldehyde chitosan.
Preferably, the solvent of the chitosan solution in step (1) is at least one of dichloromethane, pyridine, dimethyl sulfoxide, tetrahydrofuran and dimethylformamide.
Preferably, the aldehyde chitosan in the step (2) is dispersed in water by ultrasonic, and the ultrasonic time is 10-30 min.
Preferably, the ratio of the aldehyde chitosan in the step (2) to water is 0.1-8 g/10 ml; more preferably 0.2 to 1.2g/10 ml.
Preferably, the mass ratio of the aldehyde chitosan to the carboxymethyl chitosan in the step (2) is (1-4): (4-20); more preferably (1-2): (4-12).
Preferably, in the carboxymethyl chitosan solution in the step (2), the ratio of the carboxymethyl chitosan to water is (0.2-2) g/(10-40) ml; more preferably (0.2 to 1.2) g/10 ml.
Preferably, the rotation speed of the uniform mixing in the step (2) is 300-800 rpm, and the time is 2-5 h.
Preferably, the carbon-supported copper in the carbon-supported copper suspension in the step (3) is prepared by the following method: mixing chitosan and citric acid according to a mass ratio of 10: 1, adding the mixture into a glacial acetic acid aqueous solution, and reacting for 2h at 100 ℃ to obtain a citric acid carbon point solution; adding a copper acetate solution and sodium hydroxide to obtain a mixed solution; adding 35% hydrazine hydrate aqueous solution by mass, stirring for 2h at 50 ℃, centrifuging, and drying to obtain carbon-supported copper; wherein the proportion of chitosan to citric acid, copper acetate, sodium hydroxide and hydrazine hydrate is 100 mg: 10 mg: 2 mmol: 80 mg: 49 mg.
More preferably, the volume percentage of the glacial acetic acid in the glacial acetic acid aqueous solution is 1%; the mass concentration of the chitosan in the glacial acetic acid aqueous solution is 1g/100 ml; the concentration of the copper acetate solution is 0.1 mol/L; the centrifugation is as follows: the centrifugation was carried out at 9800rpm for 15min each time, and the centrifugation was repeated 6 times.
Preferably, the particle size of the copper-loaded carbon in the copper-loaded carbon suspension in the step (3) is 1-500 nm.
Preferably, in the copper-loaded carbon suspension in the step (3), the ratio of the copper-loaded carbon to water is 1-8 mg/ml; more preferably 1 to 3 mg/ml.
Preferably, the volume ratio of the copper-supported carbon suspension to the carboxymethyl chitosan-aldehyde chitosan mixed solution in the step (3) is 2: (5-40); more preferably 2: 14.
preferably, in the step (3), the carbon-supported copper suspension is added into the carboxymethyl chitosan-aldehyde chitosan mixed solution within 10-20 min.
Preferably, in the step (3), the stirring speed is 300-1200 rpm, and the stirring time in a dark state is 8-16 h.
Preferably, the light-shielding standing time in the step (3) is 6-24 h.
Preferably, the bacteriostatic absorbable medical soft tissue suture prepared in the step (3) is prepared by the following method: and (3) filling the gel liquid obtained after the continuous light-proof stirring into an injector, standing in the dark to form a gel state, solidifying to obtain the chitosan copper-based hydrogel, injecting the chitosan copper-based hydrogel into glycerol, dehydrating, washing and drying to obtain the antibacterial absorbable medical soft tissue suture.
Preferably, the size of the chitosan copper-based hydrogel in the step (3) is about 10mm × 5mm × 3 mm.
Preferably, the chitosan copper-based hydrogel in the step (3) is stretched to prepare a copper hydrogel wire material, the stretching speed is 5-20 mm/min, and the stretching strain is 2000-4000%.
More preferably, the stretching is performed in the axial direction by using a universal stretcher.
The antibacterial absorbable medical soft tissue suture prepared by the method.
The application of the bacteriostatic absorbable medical soft tissue suture line in the preparation of medicines.
Preferably, the bacteriostatic absorbable medical soft tissue suture is applied to preparation of medicines as a carrier.
Compared with the prior art, the invention has the following advantages and beneficial effects:
(1) the invention provides a new means for preparing a suture, and provides a method for preparing a soft tissue suture from a hyper-stretched hydrogel for the first time, wherein the suture has good mechanical properties, high biocompatibility and antibacterial property of a conventional suture.
(2) The suture provided by the invention has high tissue suitability, can absorb water and swell when meeting tissue fluid to fill a large pore passage caused by a needle head during suture, forms a tissue fixing effect, and can greatly reduce the problem that the suture is not fixed and is easy to cause tissue strain due to large suture passage and thin suture; and the suture has better absorbability, and can avoid secondary injury to patients caused by suture removal.
(3) The invention provides an application of preparing bacteriostatic absorbable suture, which can be used for repairing soft tissues such as liver, ovary and abdominal wall; the good antibacterial property can reduce the generation of inflammatory reaction and the formation of scar tissues; the excellent fit can prevent the formation of tissue tears; the absorbable performance can reduce the secondary damage to the patient caused by the stitch removal.
Drawings
FIG. 1 is a schematic drawing of the suture prepared in example 1, the left being before drawing and the right being after drawing.
FIG. 2 is a graph showing the swelling ratio in water of the suture prepared in example 2.
FIG. 3 is a graph showing the suture effect of the suture prepared in example 4 on mouse liver, wherein Blank is a sham-operated group, i.e., an abdominal wall only-incised group, control is a liver only-incised group, cotton is a cotton suture group, and Cu-hydrogel is a gel suture group.
Detailed Description
The present invention will be described in further detail with reference to examples and drawings, but the embodiments of the present invention are not limited thereto.
Those who do not specify specific conditions in the examples of the present invention follow conventional conditions or conditions recommended by the manufacturer. The raw materials, reagents and the like which are not indicated for manufacturers are all conventional products which can be obtained by commercial purchase.
The preparation method of the carbon-supported copper in the embodiment of the invention comprises the following steps: mixing 1g of chitosan and 0.1g of citric acid, dissolving in 1% glacial acetic acid solution by volume percentage, fixing the volume to 100mL, transferring to a polytetrafluoroethylene hydrothermal reaction kettle, and reacting at 100 ℃ for 2h to obtain 100mL of citric acid carbon point solution; adding 80mg of sodium hydroxide into 20mL0.1mol/L of copper acetate solution, mixing with 10mL of citric acid carbon point solution to obtain carbon point solution, and metering the volume to 80mL to obtain mixed solution; adding 0.14mL of 35% hydrazine hydrate in percentage by mass, stirring for 2h at 50 ℃, after the reaction is finished, centrifuging for 15min at 9800rpm for 6 times, separating, and drying in vacuum at normal temperature to obtain the carbon-supported copper powder (namely the carbon-supported mesomorphic copper powder).
Example 1
A preparation method of a bacteriostatic absorbable suture comprises the following steps:
(1) dissolving 2.5g of chitosan (molecular weight is 1000) in 40ml of dimethyl sulfoxide (DMSO), adding 1.5g of p-aldehyde benzoic acid, 10mg of 4-Dimethylaminopyridine (DMAP) and 5mg of dicyclohexylcarbodiimide under the protection of nitrogen, reacting for 24h at room temperature and 25 ℃, adding water for precipitation, filtering, washing with water for multiple times, drying, and dialyzing for 3 days by using a dialysis bag with molecular weight of 1000 to obtain the grafted and modified aldehyde chitosan;
(2) dissolving 0.6g carboxymethyl chitosan powder in 10ml deionized water, stirring at 800rpm for 4h to completely dissolve to form a light yellow solution;
(3) dispersing 0.1g of graft-modified aldehyde chitosan into 5ml of deionized water, performing ultrasonic treatment for 10min to uniformly disperse the aldehyde chitosan, slowly adding the aldehyde chitosan into a carboxymethyl chitosan solution, and stirring the mixture at 800rpm for 2h to obtain a uniform solution, thereby obtaining a carboxymethyl chitosan-graft-modified aldehyde chitosan solution;
(4) dissolving 2mg of carbon-supported mesomorphic copper powder (with particle size of 1-500nm) in 2ml of water, performing ultrasonic treatment for 15min, and uniformly dispersing to form a suspension;
(5) and (3) dropwise adding 2ml of the carbon-supported copper suspension prepared in the step (4) into 14ml of carboxymethyl chitosan-graft modified aldehyde chitosan solution under stirring for 15min under the condition of 1200rmp, stirring for 12h in the dark, pouring into a rectangular polytetrafluoroethylene mold with the length and the thickness of 10mm multiplied by 5mm multiplied by 3mm, standing for 6h in the dark, and longitudinally stretching by using a universal testing machine at a stretching rate of 20mm/min as shown in figure 1.
Example 2
A preparation method of a bacteriostatic absorbable suture comprises the following steps:
(1) dissolving 2.5g of chitosan (molecular weight is 1000) in 40ml of dimethyl sulfoxide (DMSO), adding 1.5g of p-aldehyde benzoic acid, 10mg of 4-Dimethylaminopyridine (DMAP) and 5mg of dicyclohexylcarbodiimide under the protection of nitrogen, reacting for 24h at room temperature and 25 ℃, adding water for precipitation, filtering, washing with water for multiple times, drying, and dialyzing for 3 days by using a dialysis bag with molecular weight of 1000 to obtain the grafted and modified aldehyde chitosan;
(2) respectively dissolving 0.4 g, 0.6 g, 0.8 g, 1.0 g and 1.2g of carboxymethyl chitosan powder in 10ml of deionized water, and stirring at 800rpm for 4 hours to completely dissolve to form a light yellow solution;
(3) dispersing 0.1g of graft-modified aldehyde chitosan into 5ml of deionized water, performing ultrasonic treatment for 10min to uniformly disperse the aldehyde chitosan, slowly adding the aldehyde chitosan into a carboxymethyl chitosan solution, and stirring the mixture at 800rpm for 2h to obtain a uniform solution, thereby obtaining a carboxymethyl chitosan-graft-modified aldehyde chitosan solution;
(4) dissolving 2mg of carbon-supported mesomorphic copper powder (with particle size of 1-500nm) in 2ml of water, performing ultrasonic treatment for 15min, and uniformly dispersing to form a suspension;
(5) under the state of stirring (1200rmp), dropwise adding 2ml of carbon-supported copper suspension prepared in the step (4) into 14ml of carboxymethyl chitosan-graft modified aldehyde chitosan solution for 12 hours in a dark place, pouring the mixture into a rectangular polytetrafluoroethylene mold with the length and the width of 10mm multiplied by 5mm multiplied by 3mm, standing the mixture for 6 hours in a dark place, performing longitudinal stretching by using a universal testing machine at a stretching rate of 10mm/min, stopping stretching when the strain reaches 2000-4000% and the formed gel line has a uniform diameter of about 0.1mm, removing the gel at two ends of the clamp, keeping the gel line at the middle section, and for convenience of observation, quickly leaching and dyeing the gel line by using methylene blue solution, and immediately drying the gel line in an oven at 50 ℃ for 2 hours;
(6) Removing the gel thread dyed in the step (5), penetrating the gel thread into a PVA tube with the diameter of 1mm, closing an opening at one end of the gel thread by using an aluminum thread, and slowly adding deionized water into the PVA tube from the other end by using an injection with the diameter of 1mm, wherein the PVA tube simulated tissue suture is a large pore passage caused by a needle head; the gel line was a suture line, deionized water simulated tissue fluid, and was found to fill the entire PVA tube after 4 min. The gel thread is proved to have high tissue suitability, and is expected to reduce the tissue stretching caused by the traditional suture.
Example 3
A preparation method of a bacteriostatic absorbable suture comprises the following steps:
(1) dissolving 2.5g of chitosan (molecular weight is 1000) in 40ml of dimethyl sulfoxide (DMF), adding 1.5g of p-aldehyde benzoic acid, 10mg of 4-Dimethylaminopyridine (DMAP) and 5mg of dicyclohexylcarbodiimide under the protection of nitrogen, reacting at room temperature of 25 ℃ for 24h, adding water for precipitation, filtering, washing with water for multiple times, drying, and dialyzing for 3 days by using a dialysis bag with molecular weight of 1000 to obtain the grafted and modified aldehyde chitosan;
(2) 1.2g of carboxymethyl chitosan powder is dissolved in 10ml of deionized water, and is stirred at 800rpm for 4 hours to be completely dissolved to form a light yellow solution;
(3) dispersing 0.2g of graft-modified aldehyde chitosan into 5ml of deionized water, performing ultrasonic treatment for 10min to uniformly disperse the aldehyde chitosan, slowly adding the aldehyde chitosan into a carboxymethyl chitosan solution, and stirring the mixture at 800rpm for 2h to obtain a uniform solution, thereby obtaining a carboxymethyl chitosan-graft-modified aldehyde chitosan solution;
(4) Dissolving 6mg of carbon-supported mesomorphic copper powder (with particle size of 1-500nm) in 2ml of water, performing ultrasonic treatment for 15min, and uniformly dispersing to form a suspension;
(5) and (3) under the stirring (1200rmp) state, dropwise adding 2ml of the carbon-supported copper suspension prepared in the step (4) into 14ml of carboxymethyl chitosan-graft modified aldehyde chitosan solution for 12h under the condition of keeping out of the sun, pouring into a 5ml syringe, standing for 6h under the condition of keeping out of the sun, injecting the gel into a beaker filled with glycerol by using the syringe, and leaching and drying the gel with 75% of ethanol for multiple times to obtain the gel suture with the diameter of 0.1mm-1mm after the gel is completely dehydrated.
Example 4
A preparation method of antibacterial absorbable suture and the repair capability thereof in soft tissues comprise the following steps:
(1) dissolving 2.5g of chitosan (molecular weight is 1000) in 40ml of dimethyl sulfoxide (DMSO), adding 1.5g of p-aldehyde benzoic acid, 10mg of 4-Dimethylaminopyridine (DMAP) and 5mg of dicyclohexylcarbodiimide under the protection of nitrogen, reacting for 24h at room temperature and 25 ℃, adding water for precipitation, filtering, washing with water for multiple times, drying, and dialyzing for 3 days by using a dialysis bag with molecular weight of 1000 to obtain the grafted and modified aldehyde chitosan;
(2) dissolving 0.2g carboxymethyl chitosan powder in 10ml deionized water, stirring at 800rpm for 4h to completely dissolve to form a light yellow solution;
(3) Dispersing 0.1g of graft-modified aldehyde chitosan into 5ml of deionized water, performing ultrasonic treatment for 10min to uniformly disperse the aldehyde chitosan, slowly adding the aldehyde chitosan into a carboxymethyl chitosan solution, and stirring the mixture at 800rpm for 2h to obtain a uniform solution, thereby obtaining a carboxymethyl chitosan-graft-modified aldehyde chitosan solution;
(4) dissolving 2mg of carbon-supported mesomorphic copper powder (with particle size of 1-500nm) in 2ml of water, performing ultrasonic treatment for 15min, and uniformly dispersing to form a suspension;
(5) under the state of stirring (1200rpm), dropwise adding 2ml of the carbon-supported copper suspension prepared in the step (4) into 14ml of carboxymethyl chitosan-graft modified aldehyde chitosan solution for 12 hours in a dark stirring manner, pouring the mixture into a rectangular polytetrafluoroethylene mold with the length and the width of 10mm multiplied by 5mm multiplied by 3mm, standing the mixture for 6 hours in a dark manner, longitudinally stretching the mixture by using a universal testing machine at a stretching rate of 10mm/min, stopping stretching when the strain reaches 2000-3000% and the uniform diameter of a formed gel line is about 0.1mm, removing gels at two ends of a clamp, keeping gel lines at middle sections, placing the gel lines in a culture dish, and irradiating the gel lines for 2 hours by using an ultraviolet lamp under an aseptic operating platform for convenient use;
(6) 20 female Wistar rats aged 18 to 20 weeks and having an average body weight of 160g were selected. The group 4 is a pseudo operation group (only an abdominal wall opening group, namely a pseudo operation group); the group of simple liver cutting; control group (cotton group); experimental group (gel line group i.e. material group); they were starved for 24 hours both before and after surgery. Animals received no antibiotic prophylaxis treatment. All experiments were performed under semi-sterile conditions. After anesthetizing the rat, all hairs on the abdominal wall were shaved, the skin was cleaned with iodine, the skin was entered into the abdomen through a 3 cm median incision, a part with a side length of 1 cm was cut from the lower edge of the left lobe, only the peritoneum was cut in the sham operation group and sutured, the liver of the rat was cut in the simple injury group and sutured without suture, the experimental group was sutured with a gel suture, and the control group was sutured with cotton. After 7 days after the operation, HE staining, Masoon staining and immunohistochemistry for liver regeneration index of Proliferating Cell Nuclear Antigen (PCNA) were performed on the liver tissues. 20 mice with average body weight of about 160g are taken, blood is taken from the heart of the rat, and the blood liver function index and the blood routine index are detected. The results showed (FIG. 3) that the gel-stitch group had the lowest aspartate Aminotransferase (AST) and phenylalanine Aminotransferase (ALT) levels (P < 0.05). In addition, there were no significant statistical differences in white blood cell count (WBC), red blood cell count (RBC), and hemoglobin concentration (HGB) in the 4 groups of rats 7 days after surgery. The 7d rats were scored for tissue adhesion and histopathology using the Knodell HAI scoring system for the livers of the 7d rats, wherein the lower the score the better, the sham group is the score of normal liver tissue, and the closer the sham group score is, the better the repair is. As shown in table 1, the tissue adhesion of the gel line was lower than that of the liver cut group and the cotton line group, and the histological score was superior to that of the liver cut group and the cotton line group.
TABLE 1 adhesion and histology scores for each group of materials in example 3
Example 5
An abdominal wall repair of bacteriostatic absorbable suture lines, comprising the following steps:
(1) dissolving 2.5g of chitosan (molecular weight is 1000) in 40ml of dimethyl sulfoxide (DMSO), adding 1.5g of p-aldehyde benzoic acid, 10mg of 4-Dimethylaminopyridine (DMAP) and 5mg of dicyclohexylcarbodiimide under the protection of nitrogen, reacting for 24h at room temperature and 25 ℃, adding water for precipitation, filtering, washing with water for multiple times, drying, and dialyzing for 3 days by using a dialysis bag with molecular weight of 1000 to obtain the grafted and modified aldehyde chitosan;
(2) 1g of carboxymethyl chitosan powder is dissolved in 10ml of deionized water, and is stirred at 800rpm for 4 hours to be completely dissolved to form a light yellow solution;
(3) dispersing 0.1g of graft-modified aldehyde chitosan into 5ml of deionized water, performing ultrasonic treatment for 10min to uniformly disperse the aldehyde chitosan, slowly adding the aldehyde chitosan into a carboxymethyl chitosan solution, and stirring the mixture at 800rpm for 2h to obtain a uniform solution, thereby obtaining a carboxymethyl chitosan-graft-modified aldehyde chitosan solution;
(4) dissolving 4mg of carbon-supported mesomorphic copper powder (with the particle size of 1-500 nm) in 2ml of water, and performing ultrasonic treatment for 15min to uniformly disperse the carbon-supported mesomorphic copper powder to form a suspension;
(5) under the state of stirring (1200rmp), dropwise adding 2ml of the carbon-supported copper suspension prepared in the step (4) into 14ml of carboxymethyl chitosan-graft modified aldehyde chitosan solution for 12 hours in a dark stirring manner, pouring the mixture into a rectangular polytetrafluoroethylene mold with the length and the width of 10mm multiplied by 5mm multiplied by 3mm, standing the mixture for 6 hours in a dark manner, and longitudinally stretching the mixture by using a universal testing machine at a stretching rate of 10mm/min, when the strain reaches 2000-3000%, and the uniform diameter of a formed gel line is about 0.1mm, stopping stretching, removing the gel at the two ends of the clamp, keeping a gel line at the middle section, placing the gel line in a culture dish, and irradiating the gel line by using an ultraviolet lamp for 2 hours under an aseptic operation table for convenient use;
(6) 20 female Wistar rats aged 18 to 20 weeks and having an average body weight of 160 g were selected. Dividing into 3 groups which are only abdominal wall opening groups respectively; a cotton thread sewing group; a gel thread suture group; rats were starved for 24 hours both before and after surgery, and animals received no antibiotic prophylaxis treatment. All experiments were performed under semi-sterile conditions. After anesthetizing the rat, shaving all hairs on the abdominal wall, cleaning the skin by using iodine, then cutting a median incision of 2 cm in the middle section of the abdomen, observing the healing condition of the abdominal wall incision 7 days after the operation, and finding that only the abdominal wall opening group is not completely healed and has partial infection phenomenon; the healing degree of abdominal wall incision of the cotton suture group is about 76%, partial infection exists, and the incision scar is obvious; the healing degree of the abdominal wall incision of the gel suture group is 84%, and few infections and scars are not obvious.
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.
Claims (10)
1. A preparation method of a bacteriostatic absorbable medical soft tissue suture is characterized by comprising the following steps:
(1) adding p-aldehyde benzoic acid, 4-dimethylaminopyridine and dicyclohexylcarbodiimide into a chitosan solution at room temperature under the protection of nitrogen or inert gas, reacting, purifying, drying and dialyzing to obtain aldehyde chitosan;
(2) dispersing the aldehyde chitosan into water, then adding the dispersed aldehyde chitosan into a carboxymethyl chitosan solution, and uniformly mixing to obtain a carboxymethyl chitosan-aldehyde chitosan mixed solution;
(3) adding the carbon-loaded copper suspension into the carboxymethyl chitosan-aldehyde chitosan mixed solution under the stirring state, continuously stirring in a dark place, standing in a dark place to form a gel state, solidifying to obtain chitosan copper-based hydrogel, and preparing the chitosan copper-based hydrogel into a copper hydrogel wire material with the diameter of 0.05-3 mm to obtain the antibacterial absorbable medical soft tissue suture;
in the step (3), the mass ratio of the carboxymethyl chitosan, the aldehyde chitosan and the carbon-supported copper is (20-1120): (5-187): (2-16).
2. The method for preparing the bacteriostatic absorbable medical soft tissue suture line according to claim 1, wherein the p-aldehyde benzoic acid, the 4-dimethylaminopyridine and the dicyclohexylcarbodiimide in the step (1) are sequentially added into the chitosan solution;
The mass ratio of the p-aldehyde benzoic acid, the 4-dimethylaminopyridine, the dicyclohexylcarbodiimide and the chitosan in the step (1) is (450.39-900.75): (1.22-12.2): (0.21-20.6): 1000, parts by weight; the mass ratio of the aldehyde chitosan to the carboxymethyl chitosan in the step (2) is (1-4): (4-20).
3. The method for preparing the bacteriostatic absorbable medical soft tissue suture line according to claim 1, wherein the reaction temperature in the step (1) is room temperature and the reaction time is 10-24 h; in the step (3), the carbon-loaded copper suspension is added into the carboxymethyl chitosan-aldehyde chitosan mixed solution within 10-20 min; and (4) standing in a dark place for 6-24 hours.
4. The method for preparing a bacteriostatic absorbable medical soft tissue suture line according to claim 1, 2 or 3, wherein the chitosan solution in the step (1) has a molecular weight of 800-5000; and (3) the particle size of the copper-loaded carbon in the copper-loaded carbon suspension is 1-500 nm.
5. The method for preparing a bacteriostatic absorbable medical soft tissue suture line according to claim 4, wherein in the chitosan solution of step (1), the ratio of chitosan to solvent is (0.6-9.6) g: (5-100) ml;
The ratio of the aldehyde chitosan to water in the step (2) is 0.1-8 g/10 ml; in the carboxymethyl chitosan solution, the ratio of carboxymethyl chitosan to water is (0.2-2) g/(10-40) ml;
in the carbon-supported copper suspension in the step (3), the ratio of the carbon-supported copper to the water is 1-8 mg/ml; the volume ratio of the carbon-supported copper suspension to the carboxymethyl chitosan-aldehyde chitosan mixed solution is 2: (5-40).
6. The method for preparing the bacteriostatic absorbable medical soft tissue suture line according to claim 4, wherein the rotation speed for mixing in the step (2) is 300-800 rpm for 2-5 h; in the step (3), the stirring speed is 300-1200 rpm, and the time for continuously stirring in a dark place is 8-16 h.
7. The method according to claim 4, wherein the bacteriostatic absorbable medical soft tissue suture obtained in step (3) is prepared by the following steps: filling the gel liquid obtained after continuously stirring in the dark place into an injector, standing in the dark place to form a gel state, solidifying to obtain chitosan copper-based hydrogel, injecting the chitosan copper-based hydrogel into glycerol, dehydrating, washing and drying to obtain the antibacterial absorbable medical soft tissue suture line;
And (3) stretching the chitosan copper-based hydrogel to prepare a copper hydrogel wire material, wherein the stretching speed is 5-20 mm/min, and the stretching strain is 2000-4000%.
8. The method for preparing a bacteriostatic absorbable medical soft tissue suture according to claim 4, wherein the solvent of the chitosan solution in step (1) is at least one of dichloromethane, pyridine, dimethyl sulfoxide, tetrahydrofuran and dimethylformamide; and (3) dispersing the aldehyde chitosan in water by ultrasonic for 10-30 min.
9. A bacteriostatic absorbable soft tissue suture prepared by the method of any one of claims 1 to 8.
10. The use of a bacteriostatic absorbable soft tissue suture according to claim 9 in the manufacture of a medicament.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112940295A (en) * | 2021-03-19 | 2021-06-11 | 华南农业大学 | Recyclable and reusable green hydrogel at room temperature and preparation method and application thereof |
| CN113024894A (en) * | 2021-04-06 | 2021-06-25 | 华南农业大学 | Sowable multifunctional gel mulching film for inhibiting weed growth and preparation and application thereof |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040143180A1 (en) * | 2001-11-27 | 2004-07-22 | Sheng-Ping Zhong | Medical devices visible under magnetic resonance imaging |
| WO2010070458A2 (en) * | 2008-12-19 | 2010-06-24 | Sofradim Production | Polysaccharide-based adhesive |
| CN102105494A (en) * | 2008-07-23 | 2011-06-22 | 的里雅斯特大学 | Nanocomposite materials based on metallic nanoparticles stabilized with branched polysaccharides |
| CN104145993A (en) * | 2014-08-04 | 2014-11-19 | 太原理工大学 | Method for preparing complex antimicrobial agent by blending chitosan and silver copper |
| CN108653796A (en) * | 2018-06-19 | 2018-10-16 | 佛山皖阳生物科技有限公司 | A kind of preparation method of antibacterial suture |
| CN108864494A (en) * | 2017-05-09 | 2018-11-23 | 中国科学院大学 | A kind of dynamic crosslinking double-network hydrogel and the preparation method and application thereof |
| CN109912850A (en) * | 2019-03-11 | 2019-06-21 | 同济大学 | Contain the self-healing hydrogel and its preparation method and application of excretion body |
| CN110591166A (en) * | 2019-08-20 | 2019-12-20 | 华南农业大学 | Self-driven artificial intelligence material, preparation method and application in imaging analysis and detection and drug controlled release |
| US10517988B1 (en) * | 2018-11-19 | 2019-12-31 | Endomedix, Inc. | Methods and compositions for achieving hemostasis and stable blood clot formation |
-
2020
- 2020-07-21 CN CN202010702439.4A patent/CN111840630B/en active Active
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040143180A1 (en) * | 2001-11-27 | 2004-07-22 | Sheng-Ping Zhong | Medical devices visible under magnetic resonance imaging |
| CN102105494A (en) * | 2008-07-23 | 2011-06-22 | 的里雅斯特大学 | Nanocomposite materials based on metallic nanoparticles stabilized with branched polysaccharides |
| WO2010070458A2 (en) * | 2008-12-19 | 2010-06-24 | Sofradim Production | Polysaccharide-based adhesive |
| CN104145993A (en) * | 2014-08-04 | 2014-11-19 | 太原理工大学 | Method for preparing complex antimicrobial agent by blending chitosan and silver copper |
| CN108864494A (en) * | 2017-05-09 | 2018-11-23 | 中国科学院大学 | A kind of dynamic crosslinking double-network hydrogel and the preparation method and application thereof |
| CN108653796A (en) * | 2018-06-19 | 2018-10-16 | 佛山皖阳生物科技有限公司 | A kind of preparation method of antibacterial suture |
| US10517988B1 (en) * | 2018-11-19 | 2019-12-31 | Endomedix, Inc. | Methods and compositions for achieving hemostasis and stable blood clot formation |
| CN109912850A (en) * | 2019-03-11 | 2019-06-21 | 同济大学 | Contain the self-healing hydrogel and its preparation method and application of excretion body |
| CN110591166A (en) * | 2019-08-20 | 2019-12-20 | 华南农业大学 | Self-driven artificial intelligence material, preparation method and application in imaging analysis and detection and drug controlled release |
Non-Patent Citations (5)
| Title |
|---|
| GANG-BIAO JIANG ET AL.: "Stable nanomicelles based on chitosan derivative: In vitro antiplatelet aggregation and adhesion properties", 《CARBOHYDRATE POLYMERS》 * |
| JIN LI ET AL.: "In situ polymerization induced supramolecular hydrogels of chitosan and poly(acrylic acid-acrylamide) with high toughness", 《MATERIALS CHEMISTRY FRONTIERS》 * |
| LUKAS GRITSCH ET AL.: "Fabrication and characterization of copper(II)-chitosan complexes as antibiotic-free antibacterial biomaterial", 《CARBOHYDRATE POLYMERS》 * |
| NISRINE HAMMI ET AL.: "Supramolecular Chemistry-Driven Preparation of Nanostructured, Transformable, and Biologically Active Chitosan-Clustered Single，Binary, and Ternary Metal Oxide Bioplastics", 《AMERICAN CHEMICAL SOCIETY》 * |
| 苏秀榕等: "用壳聚糖制备可吸收性手术缝合线的研究", 《辽宁师范大学学报(自然科学版)》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112940295A (en) * | 2021-03-19 | 2021-06-11 | 华南农业大学 | Recyclable and reusable green hydrogel at room temperature and preparation method and application thereof |
| CN113024894A (en) * | 2021-04-06 | 2021-06-25 | 华南农业大学 | Sowable multifunctional gel mulching film for inhibiting weed growth and preparation and application thereof |
| CN113024894B (en) * | 2021-04-06 | 2022-06-28 | 华南农业大学 | Sowing type multifunctional gel mulching film for inhibiting weed growth and preparation and application thereof |
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