CN112516372A

CN112516372A - Composite drug-loaded fiber for absorbable surgical suture

Info

Publication number: CN112516372A
Application number: CN202011259609.2A
Authority: CN
Inventors: 吴焕岭; 李子银; 林玲
Original assignee: Yancheng Institute of Technology
Current assignee: Yancheng Institute of Technology
Priority date: 2020-11-12
Filing date: 2020-11-12
Publication date: 2021-03-19

Abstract

The existing absorbable suture line has few varieties and has the defect of difficult lifting, such as: naturally absorbable sutures are low in strength and risk producing rejection reactions, while synthetic absorbable sutures are degraded in vivo for too long. In order to solve the problems, the invention provides the composite drug-loaded fiber for the absorbable suture line, so as to make up the defects of the existing suture line, avoid the pain of the patient in removing the suture line after the operation and reduce the infection risk. The drug-loaded fiber is prepared by compounding a main material, a reinforcing material, a pore-forming agent, a coating material and an anti-inflammatory, antibacterial and anticoagulant drug and combining processes of spinning, coating and the like. The fiber has many beneficial effects: the surface structure is uniform and smooth; the diameter can be regulated; has a porous internal structure; the product has good mechanical strength, extensibility, toughness and tensile property; has excellent biocompatibility; has more ideal in vivo degradation time; has good drug slow release performance, and achieves the effects of anti-inflammation, antibiosis or anticoagulation in the early stage of wound suture.

Description

Composite drug-loaded fiber for absorbable surgical suture

Technical Field

The invention relates to the field of biomedical materials, in particular to a composite drug-loaded fiber for an absorbable surgical suture.

Background

Absorbable sutures are commonly used for suturing soft and intradermal tissues in gynecology, obstetrics, surgery, orthopedics, urology, pediatric surgery, stomatology, otorhinolaryngology, ophthalmic surgery, and the like. The absorbable suture is a novel suture material which can be degraded and absorbed by a human body after being implanted into human tissues in the process of surgical suture, does not need to be removed, and avoids the pain of removing the suture. At present, the absorbable catgut suture is divided into catgut suture, high molecular chemical synthetic suture and pure natural collagen suture according to the absorbable degree. Compared with non-absorbable suture, the absorbable suture has obvious advantages, can be absorbed and avoids the pain of removing the suture. The disadvantages are also evident: according to different materials, the biodegradation time is different, and the biodegradation time is different, namely the biodegradation time is one week, and the biodegradation time is more than 90 days; the strength is not enough, so that the suture is not suitable for tissues with larger suture tension; occasional rejection reactions for natural materials; less varieties, etc. Non-absorbable sutures present more potential problems: rough surface, easy swelling, easy adhesion, easy deformation, easy infection, easy secondary damage during stitch removal and the like. Therefore, there is an urgent need to develop new species with good biocompatibility, high mechanical properties and anti-infection properties to overcome the defects and shortcomings of the existing surgical sutures.

Collagen, sodium alginate, chitosan, chitin and the like are natural biomass which can be degraded in vivo, have good biocompatibility and can be degraded and absorbed in vivo; the novel materials such as Polycaprolactone (PCL) and a copolymer thereof, namely poly-L-lactide-caprolactone (PLCL), polylactic acid (PLA) and a copolymer thereof, namely polylactic-co-glycolic acid (PLGA), are chemically synthesized biodegradable high-molecular polymers, and the polyester synthetic materials can be degraded in a non-toxic manner in an ester hydrolysis manner and have good mechanical toughness. The composite drug-loaded fiber has high mechanical performance, good biocompatibility, excellent anti-inflammatory, antibacterial or anticoagulant performance and is suitable for absorbable suture, and a new idea is developed for the development and application of novel surgical sutures. The research on the aspect has not been reported, namely the invention content of the invention.

Disclosure of Invention

In order to alleviate the defects that the existing absorbable suture line is few in variety and difficult to promote, for example, the natural absorbable suture line is not enough in strength and not suitable for tissues with larger suture tension and has potential risks of generating rejection reaction, the in-vivo degradation time of the synthetic absorbable suture line is too long, potential biological safety hazards exist, and the development of new varieties of suture lines is urgently needed to make up the defects and shortcomings of the existing surgical suture lines. In order to solve the problems, the technical scheme to be solved by the invention is to provide the novel composite drug-loaded fiber capable of absorbing suture lines and having good biocompatibility, high mechanical property and anti-inflammatory, antibacterial and anticoagulant properties, and the preparation process thereof, so that the pain of patient in postoperative suture line removal is avoided, and the infection risk is reduced.

The composite drug-loaded fiber for the absorbable surgical suture is characterized by being prepared from a main material, a reinforcing material, a pore-forming agent, a coating material and an anti-inflammatory, antibacterial and anticoagulant drug which are compounded according to a certain proportion and combined with wet spinning, coating and in-situ generation processes; specifically, the main material is compounded by one or more of proteins such as in-vivo degradable natural biomass-type I Collagen (COL), silk Fibroin (fibriin) and the like and one or more of chemically synthesized biodegradable high molecular polymer-Polycaprolactone (PCL) and copolymer thereof poly L-lactide-caprolactone (PLCL), polylactic acid (PLA) and copolymer thereof polylactic acid-glycolic acid copolymer (PLGA); the reinforcing and toughening materials are nano carbon materials of Graphene Oxide (GO), single-walled carbon nanotube (SWNT) and fullerene (C)₆₀Or C₇₀) One or more of the following; the pore-forming agent is one or more of materials or medicaments with good biocompatibility, such as polyethylene glycol (PEG), Vitamin E Acetate (VEA), curcumin (Cur), lecithin (lecithin) and the like; the coating material is composed of one or more of Sodium Alginate (SA), Carboxylated Chitosan (CCTS) and the like; the anti-inflammatory, antibacterial and anticoagulant drugs carried in the coating material are Metronidazole (MNZ),One or more of Chloramphenicol (CAP), diclofenac sodium (DFS), Ciprofloxacin (CIP), Ketoprofen (KET), heparin (UFH), etc.

The invention also provides a preparation method of the composite drug-loaded fiber for absorbable surgical suture, which comprises the following steps:

step (1): preparing a spinning solution;

step (2): wet spinning;

and (3): preparing a drug-loaded coating solution, and performing coating finishing;

and (4): and carrying out subsequent treatment on the drug-loaded fiber after the coating is finished.

The preparation method is characterized in that in the step (1), each component of the spinning solution is prepared respectively, and then mixing and compounding are carried out, specifically, firstly, a mixed solvent of Hexafluoroisopropanol (HFIP) and trifluoroacetic acid (TFA) with a certain proportion is adopted to carry out normal temperature dissolution on one or more of Collagen (COL), silk Fibroin (fibriin) and the like which are natural biomass capable of being degraded in vivo, so as to obtain a No. 1 spinning solution with the concentration of 5-20% (w/v), and the 1 spinning solution is sealed and stored; dissolving one or more of Polycaprolactone (PCL) and a copolymer thereof (PLCL), polylactic acid (PLA) and a copolymer thereof (PLGA) which are chemically synthesized biodegradable high molecular polymers at normal temperature by using the same solvent to obtain a No. 2 spinning solution with the concentration of 8-15% (w/v), and sealing and storing; using the same solvent to make the reinforced and toughened materials of Graphene Oxide (GO), single-walled carbon nanotube (SWNT) and fullerene (C)₆₀Or C₇₀) One or more of the components are subjected to ultrasonic dispersion at normal temperature to form 3 # homogeneous dispersion liquid with the concentration of 5% (w/v), and the 3 # homogeneous dispersion liquid is sealed and stored; dissolving one or more of polyethylene glycol (PEG), Vitamin E Acetate (VEA), curcumin (Cur), lecithin (lecithin) and the like which are porogens with good biological safety in the same solvent at normal temperature to form a No. 4 porogenic agent solution with the concentration of 5% (w/v), and sealing and storing. Mixing No. 1 spinning solution, No. 2 spinning solution, No. 3 homogeneous dispersion solution and No. 4 pore-forming agent solution in a volume ratio of (10-20): (1-5): in a dense mannerMixing under sealed condition, stirring, sealing and storing.

The preparation method is characterized in that in the step (2), because the selected material is not suitable for melt-blowing, the fiber is prepared by adopting a wet spinning process, specifically, after the fiber is sprayed out from a spinneret orifice, the fiber firstly enters a first coagulating bath, then enters a second coagulating bath and then enters a third coagulating bath under the action of a drawing force, and in order to promote the bidirectional diffusion of a solvent, the first coagulating bath adopts a mixed system of methanol and water at 5 ℃ as the coagulating bath, wherein the volume ratio of the methanol to the water is (2: 1) - (4: 1); a mixed system of methanol and water at the temperature of 10-15 ℃ is adopted as a coagulation bath in the second coagulation bath, wherein the volume ratio of the methanol to the water is 1: 1; the third coagulating bath adopts pure water with the temperature of 25 ℃ as coagulating bath; the draft ratio of the three-stage draft is 1: (2-4): (4-10) winding the steel wire around a winding roller.

The preparation method is characterized in that in the step (3), the fiber in the step (2) is subjected to drug-loaded coating processing, the fourth bath is a drug-loaded coating bath, the fifth bath is used for coating fixation by adopting an in-situ generation principle and method, the drug-loaded coating fixation bath is short, and specifically, water is used as a solvent to carry out the following steps of (0-5): (5-0) preparing an aqueous solution with the concentration of 0.5-1% (w/v), mixing 0.25-0.5% (w/v) of a sodium carbonate aqueous solution according to the volume ratio of 1:1, uniformly mixing, adding one or more of anti-inflammatory antibacterial anticoagulant medicaments such as Metronidazole (MNZ), Chloramphenicol (CAP), Ciprofloxacin (CIP), Ketoprofen (KET), diclofenac sodium (DFS) and heparin (UFH) with the total volume of 5-10%, uniformly mixing, and placing the mixture as a drug-carrying coating bath in a fourth bath tank; the fifth bath, namely the drug-loaded coating fixation bath, consists of 0.25-0.5% (w/v) of calcium chloride or calcium phosphate aqueous solution, and is added with one or more of Metronidazole (MNZ), Chloramphenicol (CAP), Ciprofloxacin (CIP), Ketoprofen (KET), heparin (UFH) and the like which are the same as the fourth bath and have the total volume of 5-10%, the fiber directly enters the drug-loaded coating solution of the fourth bath from a winding roller after passing through the third coagulation bath, and then enters the coating fixation bath in the fifth bath, and the drafting ratio of the third, fourth and fifth winding rollers is 1: 1: winding the composite drug-loaded fiber on a winding roller to form wet composite drug-loaded fiber for absorbing surgical suture.

The preparation method is characterized in that in the step (4), the fibers finished by the medicine-carrying coating in the step (3) are subjected to subsequent treatment, specifically, the composite medicine-carrying fibers are subjected to subsequent suture line preparation, and then the composite medicine-carrying fibers can be subjected to ultraviolet sterilization and wet vacuum storage; and the dried product can also be stored in a dry state, and the method comprises the steps of drying the product in a vacuum constant-temperature drying oven at the temperature of 30-40 ℃ for 24-48 h, or putting the product in a freeze dryer for vacuum freeze drying for 24-48 h, and performing ultraviolet sterilization and vacuum storage.

Advantageous effects

Due to the adoption of the technical scheme, compared with the prior art, the invention has the following advantages and positive effects:

(1) the composite drug-loaded fiber for absorbable surgical sutures has a good, uniform and smooth fiber surface structure, is uniform in evenness, and can be regulated to have a fiber diameter within a range of 20-200 mu m according to a process; the porous material has a porous internal structure, and the internal aperture can be regulated and controlled within the range of 50-200 nm;

(2) the composite drug-loaded fiber for the absorbable surgical suture has good mechanical strength (more than or equal to 3.5 cN/dtex), extensibility (elongation of 8-15%), toughness and excellent tensile property;

(3) the composite drug-loaded fiber for the absorbable surgical suture can be prepared into a monofilament absorbable suture according to the requirements of suture tissue and mechanical strength, and can also be prepared into a multifilament single-strand or multifilament multi-strand absorbable suture by means of a textile technology;

(4) the composite drug-loaded fiber for absorbable surgical sutures has excellent biocompatibility, can be degraded and absorbed in human tissues without toxicity, the cytotoxic reaction is less than level I, the skin sensitization rate is 0 percent, and the hemolysis rate is less than 5 percent;

(5) the composite drug-loaded fiber for the absorbable surgical suture line has more ideal degradation time-30-60 days in vivo, the complete surface structure can enable the fiber to keep higher fiber mechanical strength performance at the initial stage of suturing, after 12-15 days, the surface structure of the fiber is almost completely degraded after the tissue is healed, and then the internal porous structure starts to be rapidly degraded or collapsed until the suture line is completely degraded within 30-60 days; the degradation time is 7-14 days longer than that of common pure natural biomass fibers, so that the potential risk that the suture is broken before tissue healing is avoided, and the degradation time is longer than that of a pure chemically synthesized degradable suture for more than 90 days;

(6) the composite drug-loaded fiber for absorbable surgical sutures has good drug slow-release performance, the drugs are released simultaneously along with the degradation of the coating and the self-diffusion of the drugs, the drug release time is 48-72 hours, and the anti-inflammatory, antibacterial or anticoagulant effects in the early stage of wound suturing can be achieved according to the treatment function of the loaded drugs.

Drawings

FIG. 1 is a scanning electron microscope image of a fiber section (internal porous structure) in the composite drug-loaded fiber in example 1 of the present invention;

fig. 2 is a scanning electron microscope image of the surface structure of the fibers in the composite drug-loaded fiber in example 1 of the present invention;

FIG. 3 is a photograph of the drug-loaded composite fiber bundles (30 bundles) in example 1 of the present invention;

fig. 4 is a drug release performance diagram of the composite drug-loaded fiber in example 1 of the present invention, and the drug release conditions are as follows: fiber 0.5 g, buffer pH =7.4 phosphate buffer.

Detailed Description

The invention is further described in the following with reference to specific examples, which are provided for the purpose of clarity and are not intended to limit the scope of the invention.

In the invention, all equipment, raw materials and the like are commercially available or commonly used raw materials in the industry. The related tests of the invention are all carried out according to national standards or industrial standards.

Example 1: an anti-inflammatory composite drug-loaded fiber for absorbable suture, namely an alginic acid/carboxylated chitosan/ketoprofen coating collagen/PLCL/graphene oxide composite drug-loaded fiber, which is abbreviated as: SA-CCTS-KET @ COL-PLCL-GO

The main material is compounded by in-vivo degradable natural biomass-type I Collagen (COL) and a chemically synthesized biodegradable high polymer-polycaprolactone copolymer (PLCL), the reinforcing and toughening material is a nano carbon material-Graphene Oxide (GO), the pore-forming agent is a material or a medicament with good biocompatibility, namely Vitamin E Acetate (VEA) and curcumin (Cur), the coating material is formed by mixing Sodium Alginate (SA) and Carboxylated Chitosan (CCTS), and the anti-inflammatory drug carried in the coating material is Ketoprofen (KET). The composite drug-loaded fiber capable of being used for absorbable surgical sutures is prepared by compounding the main material, the reinforcing material, the pore-forming agent, the coating material and the anti-inflammatory drug and combining wet spinning, coating and in-situ generation processes.

Step (1): and preparing spinning solution. Preparing each component of the spinning solution respectively, and then mixing and compounding. Specifically, firstly, a mixed solvent of Hexafluoroisopropanol (HFIP) and trifluoroacetic acid (TFA) is adopted to dissolve Collagen (COL) which is a natural biomass capable of being degraded in vivo at normal temperature to obtain a No. 1 spinning solution with the concentration of 10% (w/v), and the spinning solution is sealed and stored; dissolving high molecular polymer-polycaprolactone copolymer (PLCL) with the same solvent at normal temperature to obtain 10% (w/v) No. 2 spinning solution, and sealing for storage; ultrasonically dispersing the reinforcing and toughening material Graphene Oxide (GO) by using the same solvent to obtain a No. 3 homogeneous dispersion liquid with the concentration of 5% (w/v), and sealing and storing; dissolving pore-forming agent-Vitamin E Acetate (VEA) and curcumin (Cur) at room temperature at volume ratio of 2:1 with the same solvent to obtain 5% (w/v) 4 # pore-forming agent solution, sealing and storing. Mixing the No. 1 spinning solution, the No. 2 spinning solution, the No. 3 homogeneous dispersion solution and the No. 4 pore-forming agent solution in the volume ratio of 10: 20: 2: 2 under a sealed condition, uniformly stirring, and sealing for storage.

Step (2): and (4) wet spinning. Specifically, the spinning solution in the step (1) is prepared by a wet spinning process, the fiber is sprayed out from a spinneret orifice, and then enters a first coagulation bath, a second coagulation bath and a third coagulation bath under the action of a drafting force, in order to promote the bidirectional diffusion of a solvent, the first coagulation bath adopts a mixed system of methanol and water at 5 ℃ as the coagulation bath, wherein the volume ratio of the methanol to the water is 2: 1; the second coagulation bath adopts a mixed system of methanol and water at 15 ℃ as the coagulation bath, wherein the volume ratio of the methanol to the water is 1: 1; the third coagulating bath adopts pure water with the temperature of 25 ℃ as coagulating bath; the draft ratio of the three-stage draft is 1: 4: 10, winding onto a winding roller.

And (3): preparing a drug-loaded coating solution, and performing coating processing on the fiber filaments in the step (2). Specifically, Sodium Alginate (SA) and Carboxylated Chitosan (CCTS) are mixed by taking water as a solvent according to a mass ratio of 1:1 preparing an aqueous solution with the concentration of 0.5% (w/v), mixing 0.25% (w/v) of sodium carbonate aqueous solution according to the volume ratio of 1:1, uniformly mixing, then adding Ketoprofen (KET) which is an anti-inflammatory drug and accounts for 5% of the total volume, uniformly mixing, and placing the mixture in a fourth bath as a drug-loaded coating bath; and then the fiber enters a coating fixation bath in a fifth bath, the bath consists of 0.25-0.5% (w/v) of calcium chloride or calcium phosphate aqueous solution, Ketoprofen (KET) which is the same as the fourth bath and has the total volume of 5% of anti-inflammatory drug is added, the fiber directly enters the drug-loaded coating solution in the fourth bath from a winding roller after passing through a third coagulation bath and then enters the coating fixation bath in the fifth bath, and the drafting ratio of the third, fourth and fifth winding rollers is 1: 1: winding the composite drug-loaded fiber on a winding roller to form wet composite drug-loaded fiber for absorbing surgical suture.

And (4): and (4) carrying out subsequent treatment on the drug-loaded fiber after the coating is finished in the step (3). Specifically, the composite drug-loaded fiber is subjected to subsequent suture preparation, and then can be subjected to ultraviolet sterilization and wet vacuum storage; and the dried product can also be stored in a dry state, and the method comprises the steps of drying the product in a vacuum constant-temperature drying oven at the temperature of 30-40 ℃ for 24-48 h, or putting the product in a freeze dryer for vacuum freeze drying for 24-48 h, and performing ultraviolet sterilization and vacuum storage. .

The composite drug-loaded fiber has the beneficial effects that: the fiber has a good, uniform and smooth fiber surface structure, is uniform in evenness, and has a fiber diameter of 50-80 mu m; has a porous internal structure, and the internal pore diameter is about 100 nm; the product has good mechanical strength (3.8 cN/dtex), extensibility (elongation of 10%) and toughness, and excellent tensile property; the absorbable suture can be prepared into a single-filament absorbable suture, or can be prepared into a multifilament single-strand or multifilament multi-strand absorbable suture by means of a weaving technology; has excellent biocompatibility, can be non-toxic degraded and absorbed in human tissues, has the cytotoxicity reaction less than level I, the skin sensitization rate of 0 percent and the hemolysis rate of less than 5 percent; the degradation time in vivo is about 50 days, the complete surface structure can keep the fiber with higher mechanical strength performance at the initial stage of suture, after 15 days, the internal porous structure starts to degrade or collapse rapidly, and the suture degrades completely in 50 days; has good drug slow release performance, releases the drug simultaneously along with the degradation of the coating and the self-diffusion of the drug, has the drug release time of about 72 hours, and achieves the anti-inflammatory effect at the early stage of wound suture.

Example 2: an antibacterial composite drug-loaded fiber for absorbable suture-alginic acid/chloramphenicol coated collagen/PLGA/graphene oxide composite drug-loaded fiber, which is abbreviated as: SA-CAP @ COL-PLGA-GO

The main material is formed by compounding in vivo degradable natural biomass-type I Collagen (COL) and a chemically synthesized biodegradable high polymer-polylactic acid copolymer (PLGA), the reinforcing and toughening material is a nano carbon material-Graphene Oxide (GO), the pore-forming agent is a material or a medicament with good biocompatibility, namely Vitamin E Acetate (VEA) and curcumin (Cur), the coating material is Sodium Alginate (SA), and the antibacterial drug carried in the coating material is Chloramphenicol (CAP). The composite drug-loaded fiber capable of being used for absorbable surgical sutures is prepared by compounding the main material, the reinforcing material, the pore-forming agent, the coating material and the antibacterial drug and combining wet spinning, coating and in-situ generation processes.

Step (1): and preparing spinning solution. Preparing each component of the spinning solution respectively, and then mixing and compounding. Specifically, firstly, a mixed solvent of Hexafluoroisopropanol (HFIP) and trifluoroacetic acid (TFA) is adopted to dissolve Collagen (COL) which is a natural biomass capable of being degraded in vivo at normal temperature to obtain a No. 1 spinning solution with the concentration of 12% (w/v), and the spinning solution is sealed and stored; dissolving PLGA as high molecular polymer in the same solvent at normal temperature to obtain No. 2 spinning solution in 10% (w/v), sealing and storing; ultrasonically dispersing the reinforcing and toughening material Graphene Oxide (GO) by using the same solvent to obtain a No. 3 homogeneous dispersion liquid with the concentration of 5% (w/v), and sealing and storing; dissolving pore-forming agent-Vitamin E Acetate (VEA) and curcumin (Cur) at room temperature at volume ratio of 2:1 with the same solvent to obtain 5% (w/v) 4 # pore-forming agent solution, sealing and storing. Mixing the No. 1 spinning solution, the No. 2 spinning solution, the No. 3 homogeneous dispersion solution and the No. 4 pore-forming agent solution in the volume ratio of 10: 10: 1:1 under a sealed condition, uniformly stirring, and sealing for storage.

Step (2): and (4) wet spinning. Specifically, after the fibers are sprayed out of a spinneret orifice, the fibers firstly enter a first coagulating bath, then enter a second coagulating bath and then enter a third coagulating bath under the action of a drawing force, and in order to promote the bidirectional diffusion of a solvent, a mixed system of methanol and water at 5 ℃ is adopted as the coagulating bath in the first coagulating bath, wherein the volume ratio of the methanol to the water is 3: 1; the second coagulation bath adopts a mixed system of methanol and water at 15 ℃ as the coagulation bath, wherein the volume ratio of the methanol to the water is 1: 1; the third coagulating bath adopts pure water with the temperature of 25 ℃ as coagulating bath; the draft ratio of the three-stage draft is 1: 3: 9, winding onto a winding roller.

And (3): preparing a drug-loaded coating solution, and performing coating processing on the fiber filaments in the step (2). Specifically, Sodium Alginate (SA) is prepared into an aqueous solution with the concentration of 0.5% (w/v) by taking water as a solvent, then 0.5% (w/v) of sodium carbonate aqueous solution is mixed in according to the volume ratio of 1:1, after uniform mixing, Chloramphenicol (CAP) which is an antibacterial drug with the total volume of 5% is added, and after uniform mixing, the chloramphenicol and the CAP are taken as a drug-carrying coating bath and placed in a fourth bath; and then the fiber enters a coating fixation bath in a fifth bath, the bath consists of 0.25-0.5% (w/v) of calcium chloride or calcium phosphate aqueous solution, the same as the fourth bath and 5% of the total volume of the anti-inflammatory drug, namely Chloramphenicol (CAP), is added, the fiber passes through a third coagulation bath and then directly enters a drug-loaded coating solution in the fourth bath from a winding roller, and then enters the coating fixation bath in the fifth bath, and the drafting ratio of the third, fourth and fifth winding rollers is 1: 1: winding the composite drug-loaded fiber on a winding roller to form wet composite drug-loaded fiber for absorbing surgical suture.

And (4): and (4) carrying out subsequent treatment on the drug-loaded fiber after the coating is finished in the step (3). Specifically, the composite drug-loaded fiber is subjected to subsequent suture preparation, and then can be subjected to ultraviolet sterilization and wet vacuum storage; and the dried product can also be stored in a dry state, and the method comprises the steps of drying the product in a vacuum constant-temperature drying oven at the temperature of 30-40 ℃ for 24-48 h, or putting the product in a freeze dryer for vacuum freeze drying for 24-48 h, and performing ultraviolet sterilization and vacuum storage.

The composite drug-loaded fiber has the beneficial effects that: the fiber has a good, uniform and smooth fiber surface structure, is uniform in evenness, and has a fiber diameter of 50-100 mu m; has a porous internal structure, and the internal pore diameter is about 100 nm; the product has good mechanical strength (3.6 cN/dtex), extensibility (elongation of 12%) and toughness, and excellent tensile property; the absorbable suture can be prepared into a single-filament absorbable suture, or can be prepared into a multifilament single-strand or multifilament multi-strand absorbable suture by means of a weaving technology; has excellent biocompatibility, can be non-toxic degraded and absorbed in human tissues, has the cytotoxicity reaction less than level I, the skin sensitization rate of 0 percent and the hemolysis rate of less than 5 percent; the degradation time in vivo is about 50 days, the complete surface structure can keep the fiber with higher mechanical strength performance at the initial stage of suture, after 15 days, the internal porous structure starts to degrade or collapse rapidly, and the suture degrades completely in 50 days; has good drug slow release performance, releases the drug simultaneously along with the degradation of the coating and the self-diffusion of the drug, has the drug release time of about 70 hours, and achieves the effect of early antibiosis of wound suture.

Example 3: an anticoagulant composite drug-loaded fiber for absorbable suture-namely, a silk fibroin/PLGA/single-wall carbon nanotube composite drug-loaded fiber with a carboxylated chitosan/heparin coating, which is abbreviated as follows: CCTS-UFH @ fibriin-PLGA-SWNT

The main material is formed by compounding degradable natural biomass in vivo, namely silk Fibroin (fibriin), and a biodegradable high polymer synthesized by chemical engineering, namely polylactic acid copolymer (PLGA), the reinforcing and toughening material is a nano carbon material, namely a single-walled carbon nanotube (SWNT), the pore-forming agent is a material with good biocompatibility, namely polyethylene glycol (PEG), the coating material is Carboxylated Chitosan (CCTS), and the anticoagulant drug carried in the coating material is heparin (UFH). The composite drug-loaded fiber capable of being used for absorbable surgical sutures is prepared by compounding the main material, the reinforcing material, the pore-forming agent, the coating material and the anticoagulant drug and combining wet spinning, coating and in-situ generation processes.

Step (1): and preparing spinning solution. Preparing each component of the spinning solution respectively, and then mixing and compounding. Specifically, firstly, a mixed solvent of Hexafluoroisopropanol (HFIP) and trifluoroacetic acid (TFA) is adopted to dissolve Collagen (COL) which is a natural biomass capable of being degraded in vivo at normal temperature to obtain a No. 1 spinning solution with the concentration of 15% (w/v), and the spinning solution is sealed and stored; dissolving PLGA as high molecular polymer in the same solvent at normal temperature to obtain No. 2 spinning solution in 10% (w/v), sealing and storing; ultrasonic dispersing the single-walled carbon nanotube (SWNT) as the reinforcing and toughening material with the same solvent to obtain 3 # homogeneous dispersion liquid with the concentration of 5% (w/v), and sealing and storing; dissolving the pore-forming agent polyethylene glycol (PEG) at room temperature at a volume ratio of 2:1 with the same solvent to form a No. 4 pore-forming agent solution with a concentration of 5% (w/v), and sealing and storing. Mixing the No. 1 spinning solution, the No. 2 spinning solution, the No. 3 homogeneous dispersion solution and the No. 4 pore-forming agent solution in a volume ratio of 10: 20: 2:1 under a sealing condition, uniformly stirring, and sealing for storage.

Step (2): and (4) wet spinning. Specifically, after the fibers are sprayed out of a spinneret orifice, the fibers firstly enter a first coagulating bath, then enter a second coagulating bath and then enter a third coagulating bath under the action of a drawing force, and in order to promote the bidirectional diffusion of a solvent, a mixed system of methanol and water at 5 ℃ is adopted as the coagulating bath in the first coagulating bath, wherein the volume ratio of the methanol to the water is 4: 1; the second coagulation bath adopts a mixed system of methanol and water at 15 ℃ as the coagulation bath, wherein the volume ratio of the methanol to the water is 1: 1; the third coagulating bath adopts pure water with the temperature of 25 ℃ as coagulating bath; the draft ratio of the three-stage draft is 1: 4: 8, winding on a winding roller.

And (3): preparing a drug-loaded coating solution, and performing coating processing on the fiber filaments in the step (2). Specifically, Sodium Alginate (SA) is prepared into an aqueous solution with the concentration of 0.5% (w/v) by taking water as a solvent, then 0.5% (w/v) of sodium carbonate aqueous solution is mixed in according to the volume ratio of 1:1, after uniform mixing, anticoagulant drug heparin (UFH) with the total volume of 5% is added, and after uniform mixing, the mixture is used as a drug-carrying coating bath and is placed in a fourth bath; and then the fiber enters a coating fixation bath in a fifth bath, the bath consists of 0.25-0.5% (w/v) of calcium chloride or calcium phosphate aqueous solution, heparin (UFH) which is the same as the fourth bath and has 5% of anticoagulant drug in total volume is added, the fiber directly enters the drug-loaded coating solution in the fourth bath from a winding roller after passing through a third coagulation bath and then enters the coating fixation bath in the fifth bath, and the drafting ratio of the third, the fourth and the fifth winding rollers is 1: 1: winding the composite drug-loaded fiber on a winding roller to form wet composite drug-loaded fiber for absorbing surgical suture.

The composite drug-loaded fiber has the beneficial effects that: the fiber has a good, uniform and smooth fiber surface structure, is uniform in evenness, and has a fiber diameter of 80-100 mu m; has a porous internal structure, and the internal pore diameter is about 50 nm; the product has good mechanical strength (3.5 cN/dtex), extensibility (elongation of 11%) and toughness, and excellent tensile property; the absorbable suture can be prepared into a single-filament absorbable suture, or can be prepared into a multifilament single-strand or multifilament multi-strand absorbable suture by means of a weaving technology; has excellent biocompatibility, can be non-toxic degraded and absorbed in human tissues, has the cytotoxicity reaction less than level I, the skin sensitization rate of 0 percent and the hemolysis rate of less than 5 percent; the degradation time in vivo is about 60 days, the complete surface structure can keep the fiber with higher mechanical strength performance at the initial stage of suture, after 15 days, the internal porous structure starts to degrade or collapse rapidly, and the suture degrades completely in 60 days; has good drug slow release performance, releases the drug simultaneously along with the degradation of the coating and the self-diffusion of the drug, has the drug release time of about 65 hours, and achieves the effect of anticoagulation at the early stage of wound suture.

The embodiments 1 to 3 described in the present invention are only descriptions of preferred embodiments of the present invention, and do not limit the concept and scope of the present invention, and various modifications and improvements made to the technical solution of the present invention by engineering techniques in the art without departing from the design concept of the present invention shall fall within the protection scope of the present invention.

Claims

1. The composite drug-loaded fiber for the absorbable surgical suture is characterized by being prepared by compounding a main material, a reinforcing material, a pore-forming agent, a coating material and an anti-inflammatory, antibacterial and anticoagulant drug according to a certain proportion and combining wet spinning, coating and an in-situ generation process; specifically, the main material is compounded by one or more of proteins such as in-vivo degradable natural biomass-type I Collagen (COL), silk Fibroin (fibriin) and the like and one or more of chemically synthesized biodegradable high molecular polymer-Polycaprolactone (PCL) and copolymer thereof poly L-lactide-caprolactone (PLCL), polylactic acid (PLA) and copolymer thereof polylactic acid-glycolic acid copolymer (PLGA); the reinforcing and toughening materials are nano carbon materials of Graphene Oxide (GO), single-walled carbon nanotube (SWNT) and fullerene (C)₆₀Or C₇₀) One or more of the following; the pore-forming agent is one or more of materials or medicaments with good biocompatibility, such as polyethylene glycol (PEG), Vitamin E Acetate (VEA), curcumin (Cur), lecithin (lecithin) and the like; the coating material is composed of one or more of Sodium Alginate (SA), Carboxylated Chitosan (CCTS) and the like; the anti-inflammatory, antibacterial and anticoagulant drug contained in the coating material is Metronidazole (MNZ) or chlorineOne or more of mycin (CAP), diclofenac sodium (DFS), Ciprofloxacin (CIP), Ketoprofen (KET), heparin (UFH), etc.

2. The absorbable surgical suture composite drug-loaded fiber according to claim 1, which is prepared by a method comprising four steps:

step (1): preparing spinning solution, specifically, respectively preparing each component of the spinning solution, mixing and compounding, firstly adopting a mixed solvent of Hexafluoroisopropanol (HFIP) and trifluoroacetic acid (TFA) to dissolve one or more of natural biomass capable of being degraded in vivo, namely Collagen (COL), silk Fibroin (fibriin) and the like at normal temperature to obtain 1 # spinning solution with the concentration of 5-20% (w/v), and sealing and storing; dissolving one or more of Polycaprolactone (PCL) and a copolymer thereof (PLCL), polylactic acid (PLA) and a copolymer thereof (PLGA) which are chemically synthesized biodegradable high molecular polymers at normal temperature by using the same solvent to obtain a No. 2 spinning solution with the concentration of 8-15% (w/v), and sealing and storing; using the same solvent to make the reinforced and toughened materials of Graphene Oxide (GO), single-walled carbon nanotube (SWNT) and fullerene (C)₆₀Or C₇₀) One or more of the components are subjected to ultrasonic dispersion at normal temperature to form 3 # homogeneous dispersion liquid with the concentration of 5% (w/v), and the 3 # homogeneous dispersion liquid is sealed and stored; dissolving one or more materials or medicaments of pore-foaming agents with good biological safety, such as polyethylene glycol (PEG), Vitamin E Acetate (VEA), curcumin (Cur), lecithin (lecithin) and the like, at normal temperature by using the same solvent to form a No. 4 pore-foaming agent solution with the concentration of 5% (w/v), and sealing and storing; mixing the No. 1 spinning solution, the No. 2 spinning solution, the No. 3 homogeneous dispersion solution and the No. 4 pore-forming agent solution in a volume ratio of (10-20) to (1-5) under a sealing condition, uniformly stirring, and sealing and storing;

step (2): wet spinning, specifically, preparing fibers from the spinning solution in the step (1) by adopting a wet spinning process, wherein the fibers are sprayed out from a spinneret orifice, and then enter a first coagulation bath, a second coagulation bath and a third coagulation bath under the action of a drawing force, in order to promote the bidirectional diffusion of a solvent, the first coagulation bath adopts a mixed system of methanol and water at 5 ℃ as the coagulation bath, and the volume ratio of the methanol to the water is (2: 1) - (4: 1); a mixed system of methanol and water at the temperature of 10-15 ℃ is adopted as a coagulation bath in the second coagulation bath, wherein the volume ratio of the methanol to the water is 1: 1; the third coagulating bath adopts pure water with the temperature of 25 ℃ as coagulating bath; the draft ratio of the three-stage draft is 1: (2-4): (4-10) winding the steel wire around a winding roller;

and (3): preparing a drug-loaded coating solution, and performing coating finishing, specifically, performing coating processing on the fiber in the step (2), wherein the fourth bath is a drug-loaded coating bath, and the fifth bath is used for coating fixation by adopting an in-situ generation principle and method, and is called a drug-loaded coating fixation bath for short; specifically, one or more of Sodium Alginate (SA), Carboxylated Chitosan (CCTS) and the like is/are mixed according to the ratio of (0-5): (5-0) preparing an aqueous solution with the concentration of 0.5-1% (w/v), mixing 0.25-0.5% (w/v) of a sodium carbonate aqueous solution according to the volume ratio of 1:1, uniformly mixing, adding one or more of anti-inflammatory antibacterial anticoagulant medicaments such as Metronidazole (MNZ), Chloramphenicol (CAP), Ciprofloxacin (CIP), Ketoprofen (KET), diclofenac sodium (DFS) and heparin (UFH) with the total volume of 5-10%, uniformly mixing, and placing the mixture as a drug-carrying coating bath in a fourth bath tank; the fifth bath, namely the drug-loaded coating fixation bath, consists of 0.25-0.5% (w/v) of calcium chloride or calcium phosphate aqueous solution, and is added with one or more of Metronidazole (MNZ), Chloramphenicol (CAP), Ciprofloxacin (CIP), Ketoprofen (KET), heparin (UFH) and the like which are the same as the fourth bath and have the total volume of 5-10%, the fiber directly enters the drug-loaded coating solution of the fourth bath from a winding roller after passing through the third coagulation bath, and then enters the coating fixation bath in the fifth bath, and the drafting ratio of the third, fourth and fifth winding rollers is 1: 1: winding the composite drug-loaded fiber on a winding roller to form wet composite drug-loaded fiber for absorbing surgical suture lines;

and (4): carrying out subsequent treatment on the fiber finished by the drug-loaded coating in the step (3), specifically, preparing a subsequent suture line on the composite drug-loaded fiber, and then carrying out ultraviolet sterilization and wet vacuum storage; and the dried product can also be stored in a dry state, and the method comprises the steps of drying the product in a vacuum constant-temperature drying oven at the temperature of 30-40 ℃ for 24-48 h, or putting the product in a freeze dryer for vacuum freeze drying for 24-48 h, and performing ultraviolet sterilization and vacuum storage.