CN113881021B - Terpolymer, suture and preparation method and application thereof - Google Patents

Terpolymer, suture and preparation method and application thereof Download PDF

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CN113881021B
CN113881021B CN202111220472.4A CN202111220472A CN113881021B CN 113881021 B CN113881021 B CN 113881021B CN 202111220472 A CN202111220472 A CN 202111220472A CN 113881021 B CN113881021 B CN 113881021B
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terpolymer
glycolide
mol
suture
caprolactone
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CN113881021A (en
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徐家林
凤鹏举
范义飞
刘逸涵
毛秦岑
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Huangpu Institute of Materials
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    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
    • C08G63/02—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds
    • C08G63/06—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds derived from hydroxycarboxylic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L17/00—Materials for surgical sutures or for ligaturing blood vessels ; Materials for prostheses or catheters
    • A61L17/06—At least partially resorbable materials
    • A61L17/10—At least partially resorbable materials containing macromolecular materials
    • A61L17/12—Homopolymers or copolymers of glycolic acid or lactic acid
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
    • C08G63/78—Preparation processes
    • D—TEXTILES; PAPER
    • D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01D—MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
    • D01D5/00—Formation of filaments, threads, or the like
    • D01D5/08—Melt spinning methods
    • D01D5/098—Melt spinning methods with simultaneous stretching
    • D—TEXTILES; PAPER
    • D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01F—CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
    • D01F6/00—Monocomponent artificial filaments or the like of synthetic polymers; Manufacture thereof
    • D01F6/78—Monocomponent artificial filaments or the like of synthetic polymers; Manufacture thereof from copolycondensation products
    • D01F6/84—Monocomponent artificial filaments or the like of synthetic polymers; Manufacture thereof from copolycondensation products from copolyesters

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Textile Engineering (AREA)
  • Medicinal Chemistry (AREA)
  • Polymers & Plastics (AREA)
  • Organic Chemistry (AREA)
  • Surgery (AREA)
  • Materials Engineering (AREA)
  • General Chemical & Material Sciences (AREA)
  • Vascular Medicine (AREA)
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  • General Health & Medical Sciences (AREA)
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Abstract

The invention relates to a terpolymer, which is prepared by copolymerizing 60-78 mol% of glycolide, 2-20 mol% of L-lactide and 20mol% of caprolactone under the catalysis of stannous octoate in terms of mole percentage. The terpolymer is obtained by ring-opening polymerization of glycolide, L-lactide and caprolactone, has good degradability and thermal property, and further, the terpolymer is melt-spun to obtain a suture thread with good mechanical property, so that the terpolymer is suitable for the biomedical field.

Description

Terpolymer, suture and preparation method and application thereof
Technical Field
The invention relates to the technical field of absorbable medical materials, in particular to a terpolymer, a suture line, a preparation method and application thereof.
Background
The absorbable medical material is widely applied to the processes of suturing wounds, ligating lumen, closing tissues, fixing implants, repairing wound surfaces and the like. The chemical composition of the water-soluble polymer is mainly biodegradable polymer, and the water-soluble polymer can be finally degraded into water and carbon dioxide which are nontoxic and harmless to human body after maintaining the mechanical strength of the human body for a certain time, and is discharged out of the body through metabolism.
L-lactide (LLA) and Glycolide (GA) have been used in the fields of controlled drug release, tissue scaffolds, bone fixation, etc. due to their controlled degradability and good biocompatibility. However, their mechanical properties of homopolymers (polylactic acid (PLLA), polyglycolic acid (PGA)) and copolymers (PLGA) are not ideal, affecting their use in the biomedical field.
Polycaprolactone (PCL) is a flexible polymer, and has been widely applied to tissue engineering and drug delivery applications due to rubbery elasticity and biocompatibility, and particularly PCL-based materials have very broad application prospects in biomedical applications.
The traditional method is to prepare the poly L-lactide-poly (glycolide/caprolactone) multiblock copolymer by respectively preparing the poly L-lactide oligomer into a hard phase and the poly (glycolide/caprolactone) copolymer into a soft phase and coupling the hard phase and the soft phase to prepare the poly L-lactide-poly (glycolide/caprolactone) multiblock copolymer, wherein the prepared copolymer has biodegradability, but the copolymer has lower tensile modulus and cannot be melt spun to prepare the suture line.
Disclosure of Invention
Based on this, it is necessary to provide a terpolymer capable of improving thermodynamic properties and a preparation method thereof, and a suture prepared by using the terpolymer and a preparation method and application thereof.
The invention provides a terpolymer, which is prepared by copolymerizing 60-78 mol% of glycolide, 2-20 mol% of L-lactide and 20mol% of caprolactone under the catalysis of stannous octoate in terms of mole percentage.
In one embodiment, the polymer is produced by copolymerizing 60 to 70mol% of the glycolide, 10 to 20mol% of the L-lactide, and 20mol% of the caprolactone, in terms of mole percent, under the catalysis of the stannous octoate.
In one embodiment, the polymer is produced by copolymerizing 72 to 78mol% of the glycolide, 2 to 8mol% of the L-lactide, and 20mol% of the caprolactone, in terms of mole percent, under the catalysis of the stannous octoate.
The invention also provides a preparation method of the terpolymer, which comprises the following steps:
weighing 60-78 mol% of glycolide, 2-20 mol% of L-lactide and 20mol% of caprolactone according to the mol percentage;
mixing part of the glycolide, the L-lactide and the caprolactone, and heating and reacting under a negative pressure state by taking stannous octoate as a catalyst to generate a prepolymer, wherein the ratio of the mass of part of the glycolide to the mass of the caprolactone is 45:55-55-45;
and adding the rest glycolide into the prepolymer, and continuing the heating reaction to obtain the terpolymer.
In one embodiment, a glycol initiator is also added during the step of forming the prepolymer.
In one embodiment, the ratio of the amount of the substance of the ester groups in the glycolide, the L-lactide, and the caprolactone to the amount of the substance of the glycol initiator is (10000 to 30000): 1.
in one embodiment, the ratio of the amount of ester group material in the glycolide, the L-lactide, and the caprolactone to the amount of stannous octoate material is (2000-5000): 1.
in one embodiment, the operation of heating the prepolymer includes: firstly, heating to 120-130 ℃, keeping the temperature until the materials are melted, continuously heating to 145-170 ℃, keeping the materials capable of stirring, and reacting for 3-6 h; and/or
The operation of the heating reaction in the formation of the terpolymer includes: heating to 190-210 deg.c and maintaining the temperature for 2-4 hr.
The invention also provides a preparation method of the suture, and the terpolymer prepared by the preparation method of any one of the above embodiment or the terpolymer prepared by the preparation method of any one of the above embodiment is melt spun.
In one embodiment, the melt temperature of the melt spinning is 150 ℃ to 180 ℃; and/or
The draft ratio of the melt spinning is 4:1-9:1; and/or
The drafting temperature of the melt spinning is 50-80 ℃.
The invention also provides a suture, which is prepared by the preparation method of the suture in any embodiment.
In one embodiment, the suture has a diameter of 100um to 149um.
The invention also provides a biomedical use of the suture according to any of the embodiments described above.
In one embodiment, the suture is used in biomedical applications for non-therapeutic purposes.
The terpolymer is obtained by ring-opening polymerization of glycolide, L-lactide and caprolactone, has good degradability and thermodynamic properties, and further, the terpolymer is melt-spun to obtain a suture thread with good mechanical properties, so that the terpolymer is suitable for the biomedical field.
Drawings
FIG. 1 is a schematic representation of a terpolymer according to one embodiment;
FIG. 2 is a physical view of a suture thread obtained by melt spinning the terpolymer of FIG. 1;
FIG. 3 is a DSC of the terpolymer of FIG. 1;
FIG. 4 is a TGA spectrum of the terpolymer of FIG. 1;
FIG. 5 is a schematic illustration of the terpolymer of FIG. 1 1 HNMR spectra.
Detailed Description
In order that the invention may be readily understood, a more complete description of the invention will be rendered by reference to the appended drawings. Preferred embodiments of the present invention are shown in the drawings. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The term "and/or" as used herein includes any and all combinations of one or more of the associated listed items.
An embodiment of the invention provides a terpolymer, which is prepared by copolymerizing 60-78 mol% of glycolide, 2-20 mol% of L-lactide and 20mol% of caprolactone under the catalysis of stannous octoate in terms of mole percentage. As shown in fig. 1, the terpolymer provided in this example was in the form of white fibers.
The terpolymer composed of the components has high purity and good degradability and thermal property.
In a specific example, the polymer is produced by copolymerizing 60 to 70mol% glycolide, 10 to 20mol% L-lactide, and 20mol% caprolactone, in terms of mole percent, under the catalysis of stannous octoate.
In a specific example, the polymer is produced by copolymerizing 72mol% to 78mol% of glycolide, 2mol% to 8mol% of L-lactide, and 20mol% of caprolactone, in terms of mole percent, under the catalysis of stannous octoate.
The embodiment of the invention also provides a preparation method of the terpolymer, which comprises the following steps S110 to S130.
S110: weighing 60-78 mol% of glycolide, 2-20 mol% of L-lactide and 20mol% of caprolactone according to the mol percentage.
In a specific example, 60mol% to 70mol% glycolide, 10mol% to 20mol% L-lactide, and 20mol% caprolactone are weighed in mole percent.
In a specific example, 72mol% to 78mol% glycolide, 2mol% to 8mol% L-lactide, and 20mol% caprolactone are weighed in mole percent.
S120: mixing part of glycolide, L-lactide and caprolactone, and heating and reacting under a negative pressure state by taking stannous octoate as a catalyst to generate a prepolymer, wherein the ratio of the amount of the substance of the part of glycolide to the amount of the substance of the caprolactone is 45:55-55:45. Stannous octoate can catalyze glycolide, L-lactide and caprolactone to carry out polymerization reaction, so that the reaction rate is improved. Part of glycolide is added to form prepolymer, which is favorable for avoiding self-polymerization of glycolide and reducing the generation of byproducts. Preferably, the ratio of the amount of partial glycolide material to the amount of caprolactone material is 50:50.
In a specific example, the ratio of the amount of ester group material in glycolide, L-lactide, and caprolactone to the amount of stannous octoate material is (2000-5000): 1. further, the ratio of the amount of the substance of the ester group in glycolide, L-lactide and caprolactone to the amount of the substance of stannous octoate is (4000 to 5000): 1.
in a specific example, a glycol initiator is also added during the step of forming the prepolymer. Wherein the diol initiator can initiate ester monomers such as glycolide, L-lactide, caprolactone and the like to carry out polymerization reaction. The glycol initiator may be, but is not limited to, one or more of 1, 4-butanediol, diethylene glycol, pentanediol, and lauryl alcohol.
In a specific example, the ratio of the amount of the substance of the ester group in glycolide, L-lactide and caprolactone to the amount of the substance of the glycol initiator is (10000 to 30000): 1. further, the ratio of the amount of the substance of the ester group in glycolide, L-lactide and caprolactone to the amount of the substance of the diol initiator is (10000 to 25000): 1.
in a specific example, the operation of heating the reaction during formation of the prepolymer includes: heating to 120-130 ℃, keeping the temperature until the materials are melted, continuously heating to 145-170 ℃, keeping the materials capable of stirring, and reacting for 3-6 h. The temperature of the material is raised to be higher than the melting temperature of the glycolide, the L-lactide and the caprolactone during melting, and then the material is gradually raised after the material is completely melted, so that the material with high reactivity is prevented from being excessively high in reactivity, for example, the glycolide is prevented from being excessively high in reactivity, and if the temperature is raised too fast, the glycolide can be subjected to self-polymerization, and byproducts are increased.
S130: adding the rest glycolide into the prepolymer, and continuing the heating reaction to obtain the terpolymer.
The prepolymer and the remaining glycolide are melted separately prior to adding the remaining glycolide. If the prepolymer is not solidified after step S120, the prepolymer does not need to be subjected to a melting step, and if solidification of the prepolymer occurs, the prepolymer is melted first. The operation of melting the prepolymer includes: the prepolymer is heated to 170 ℃ to 190 ℃ and kept at the temperature until the prepolymer is melted.
In one specific example, the operation of heating the reaction to form the terpolymer includes: heating to 190-210 deg.c and maintaining the temperature for 2-4 hr.
Further, step S140 may be further included.
S140: purifying the terpolymer to obtain the high-purity terpolymer.
In one specific example, the operation of purifying the terpolymer includes: adding a first organic solvent into the terpolymer to dissolve the terpolymer, filtering, settling the filtrate with a second organic solvent, filtering again, and drying the filter residue for 24-48 h under the vacuum condition of 100-120 ℃.
Wherein the first organic solvent can be one or a mixture of more of hexafluoroisopropanol, trifluoroacetic acid, tetrachloroethane and dimethyl sulfoxide.
The second organic solvent may be, but is not limited to, one or more of methanol, ethanol, isopropanol, and butanol.
In a specific example, when the terpolymer is dissolved with the first organic solvent, the ratio of the weight of the terpolymer to the volume of the first organic solvent is 1g: (5-10) mL.
The invention also provides a preparation method of the suture, and the terpolymer or the terpolymer prepared by the preparation method of the terpolymer in any specific example is subjected to melt spinning.
In a specific example, the melt temperature of the melt spinning is 150 ℃ to 180 ℃.
In a specific example, the draw ratio of the melt spinning is 4:1 to 9:1.
In a specific example, the draw temperature of the melt spinning is 50 ℃ to 80 ℃.
As shown in FIG. 2, the invention further provides a suture, which is prepared by the preparation method of the suture in any specific example.
In one specific example, the suture thread has a diameter of 100um to 149um. The suture has good toughness and is not easy to break, and meets the requirements of national standard YY1116-2020 on breaking strength of B-class (single strand) sutures.
The invention also provides the use of a suture according to any of the examples above in biomedical applications. It will be appreciated that the above described suture may be used in biomedical applications for non-therapeutic purposes.
The high-purity terpolymer is obtained by ring-opening polymerization of glycolide, L-lactide and caprolactone, and has good degradation performance and thermal performance, and furthermore, the terpolymer is melt-spun to obtain a suture thread with good mechanical performance, so that the high-purity terpolymer is suitable for the biomedical field.
The following are specific examples. In the following examples, all materials are commercially available unless otherwise specified.
Example 1:
the mass ratio of glycolide to L-lactide to caprolactone=60% to 20% terpolymer and suture were prepared.
Step one: 11.61g of glycolide (0.1 mol, molecular weight: 116.07 g/mol), 14.41g L-lactide (0.1 mol, molecular weight: 144.13 g/mol), 11.41g of caprolactone (0.1 mol, molecular weight: 114.14 g/mol), 1.8mg of 1, 4-butanediol (0.02 mmol, molecular weight: 90.12 g/mol), 40.5mg of stannous octoate (0.1 mmol, molecular weight: 405.1 g/mol) were accurately weighed, and three ester monomers, glycol initiators, and catalysts were added to the three-necked flask.
Step two: repeatedly introducing nitrogen into the three-mouth bottle and extracting for 5 times, placing the three-mouth bottle in an oil bath after extracting, mechanically stirring, heating to 130 ℃ to enable the ester monomer to be completely melted to a clear and transparent state, heating the system to 145 ℃, observing an experimental state during the process, and continuously heating to be capable of stirring if the viscosity of the material is too high and difficult to stir, and reacting for 6 hours to form the prepolymer.
Step three: heating to 170 ℃ to melt the prepolymer, adding 23.21g (0.2 mol) of melted glycolide monomer, heating to 200 ℃ to react for 2 hours after the mixture is completely melted to obtain the terpolymer, and crushing the terpolymer by a three-necked bottle when the terpolymer is cooled to a room temperature state.
Step four: crushing the terpolymer by using a crusher, adding hexafluoroisopropanol according to the proportion of the weight of the terpolymer to the volume of the first organic solvent of 1g to 10mL, mechanically stirring until the terpolymer is completely dissolved, filtering the solution by using a sand core funnel, settling the filtrate into a methanol solution to obtain white filiform fibers, and drying the white filiform fibers under the vacuum condition of 100 ℃ for 24 hours to constant weight to obtain the purified terpolymer.
Step five: and (3) carrying out melt spinning on the purified terpolymer, wherein the melting temperature is 170 ℃, the draft ratio is 9:1, the draft temperature is 60 ℃, and the suture line is obtained after heat setting.
Example 2:
the mass ratio of glycolide to L-lactide to caprolactone=75 mol% to 5mol% to 20mol% terpolymer and suture were prepared.
Step one: 4.64g of glycolide (0.04 mol, molecular weight: 116.07 g/mol), 1.44g L-lactide (0.01 mol, molecular weight: 144.13 g/mol), 4.58g of caprolactone (0.04 mol, molecular weight: 114.14 g/mol), 1.8mg of 1, 4-butanediol (0.02 mmol, molecular weight: 90.12 g/mol), 16.2mg of stannous octoate (0.04 mmol, molecular weight: 405.1 g/mol) and a catalyst were accurately weighed into a three-necked flask.
Step two: step two of example 1 was repeated.
Step three: heating to 170 ℃ to melt the prepolymer, adding 12.77g (0.11 mol) of melted glycolide monomer, heating to 200 ℃ to react for 2 hours after the mixture is completely melted to obtain the terpolymer, and crushing the terpolymer by a three-necked bottle when the terpolymer is cooled to a room temperature state.
Step four: step four of example 1 was repeated.
Step five: step five of example 1 was followed.
Example 3:
the mass ratio of glycolide to L-lactide to caprolactone=70 mol%:10mol%:20mol% of the terpolymer and the suture were prepared.
Step one: 4.64g of glycolide (0.04 mol, molecular weight: 116.07 g/mol), 2.88g L-lactide (0.02 mol, molecular weight: 144.13 g/mol), 4.58g of caprolactone (0.04 mol, molecular weight: 114.14 g/mol), 1.8mg of 1, 4-butanediol (0.02 mmol, molecular weight: 90.12 g/mol), 16.2mg of stannous octoate (0.04 mmol, molecular weight: 405.1 g/mol) and a catalyst were accurately weighed into a three-necked flask.
Step two: step two of example 1 was repeated.
Step three: heating to 170 ℃ to melt the prepolymer, adding 11.61g (0.1 mol) of melted glycolide monomer, heating to 200 ℃ to react for 2 hours after the mixture is completely melted to obtain the terpolymer, and crushing the terpolymer by a three-necked bottle when the terpolymer is cooled to a room temperature state.
Step four: step four of example 1 was repeated.
Step five: step five of example 1 was followed.
Comparative example 1:
the mass ratio of glycolide to L-lactide to caprolactone=80 mol%:10mol% of the terpolymer and the suture were prepared.
Step one: 5.80g of glycolide (0.05 mol, molecular weight: 116.07 g/mol), 7.21g L-lactide (0.05 mol, molecular weight: 144.13 g/mol), 5.71g of caprolactone (0.05 mol, molecular weight: 114.14 g/mol), 1.8mg of 1, 4-butanediol (0.02 mmol, molecular weight: 90.12 g/mol), 40.5mg of stannous octoate (0.1 mmol, molecular weight: 405.1 g/mol) and a catalyst were accurately weighed into a three-necked flask.
Step two: step two of example 1 was repeated.
Step three: heating to 170 ℃ to melt the prepolymer, adding 40.6g (0.35 mol) of melted glycolide monomer, heating to 200 ℃ to react for 2 hours after the mixture is completely melted to obtain the terpolymer, and crushing the terpolymer by a three-necked bottle when the terpolymer is cooled to a room temperature state.
Step four: step four of example 1 was repeated.
Step five: step five of example 1 was followed.
Comparative example 2:
the mass ratio of glycolide to L-lactide to caprolactone=60% to 10% to 30% terpolymer and suture were prepared.
Step one: 17.41g of glycolide (0.15 mol, molecular weight: 116.07 g/mol), 7.21g L-lactide (0.05 mol, molecular weight: 144.13 g/mol), 17.12g of caprolactone (0.15 mol, molecular weight: 114.14 g/mol), 1.8mg of 1, 4-butanediol (0.02 mmol, molecular weight: 90.12 g/mol), 40.5mg of stannous octoate (0.1 mmol, molecular weight: 405.1 g/mol) and a catalyst were accurately weighed into a three-necked flask.
Step two: step two of example 1 was repeated.
Step three: heating to 170 ℃ to melt the prepolymer, adding 17.41g (0.15 mol) of melted glycolide monomer, heating to 200 ℃ to react for 2 hours after the mixture is completely melted to obtain the terpolymer, and crushing the terpolymer by a three-necked bottle when the terpolymer is cooled to a room temperature state.
Step four: step four of example 1 was repeated.
Step five: step five of example 1 was followed.
Comparative example 3:
the mass ratio of glycolide to L-lactide to caprolactone=90% to 10% terpolymer and suture were prepared.
Step one: 5.8g of glycolide (0.05 mol, molecular weight: 116.07 g/mol), 7.21g L-lactide (0.05 mol, molecular weight: 144.13 g/mol), 5.71g of caprolactone (0.05 mol, molecular weight: 114.14 g/mol), 1.8mg of 1, 4-butanediol (0.02 mmol, molecular weight: 90.12 g/mol), 40.5mg of stannous octoate (0.1 mmol, molecular weight: 405.1 g/mol) were accurately weighed, and three ester monomers, glycol initiators, and catalyst were added to the three-necked flask.
Step two: step two of example 1 was repeated.
Step three: heating to 170 ℃ to melt the prepolymer, adding 46.42g (0.4 mol) of melted glycolide monomer, heating to 200 ℃ to react for 2 hours after the mixture is completely melted to obtain the terpolymer, and crushing the terpolymer by a three-necked bottle when the terpolymer is cooled to a room temperature state.
Step four: step four of example 1 was repeated.
Step five: step five of example 1 was followed.
Comparative example 4:
the mass ratio of glycolide to L-lactide to caprolactone=99.8 mol% to 0.1mol% was used for the preparation of the terpolymer and the suture.
Step one: 0.12g of glycolide (0.001 mol, molecular weight: 116.07 g/mol), 0.14g L-lactide (0.001 mol, molecular weight: 144.13 g/mol), 0.14g of caprolactone (0.001 mol, molecular weight: 114.14 g/mol), 1.8mg of 1, 4-butanediol (0.02 mmol, molecular weight: 90.12 g/mol), 40.5mg of stannous octoate (0.1 mmol, molecular weight: 405.1 g/mol) were accurately weighed, and three ester monomers, glycol initiators, and catalysts were added to the three-necked flask.
Step two: step two of example 1 was repeated.
Step three: heating to 170 ℃ to melt the prepolymer, adding 115.7g (0.997 mol) of melted glycolide monomer, heating to 200 ℃ to react for 2 hours after the mixture is completely melted to obtain the terpolymer, and crushing the terpolymer by a three-necked bottle when the terpolymer is cooled to a room temperature state.
Step four: step four of example 1 was repeated.
Step five: step five of example 1 was followed.
Comparative example 5:
the ratio of the amounts of the substances was glycolide to L-lactide to caprolactone=33.3 mol%:33.3mol%:33.4mol% terpolymer and suture preparation.
Step one: 11.6g of glycolide (0.1 mol, molecular weight: 116.07 g/mol), 14.4. 14.4g L-lactide (0.1 mol, molecular weight: 144.13 g/mol), 11.4g of caprolactone (0.1 mol, molecular weight: 114.14 g/mol), 1.8mg of 1, 4-butanediol (0.02 mmol, molecular weight: 90.12 g/mol), 40.5mg of stannous octoate (0.1 mmol, molecular weight: 405.1 g/mol) were accurately weighed, and three ester monomers, glycol initiators, and catalysts were added to the three-necked flask.
Step two: repeatedly introducing nitrogen into the three-mouth bottle and extracting for 5 times, placing the three-mouth bottle into an oil bath after extracting, mechanically stirring, heating to 130 ℃ to enable the ester monomer to be completely melted to a clear and transparent state, heating the system to 200 ℃ to react for 2 hours, and crushing the three-mouth bottle to obtain the terpolymer when cooling to a room temperature state.
Step three: step four of example 1 was repeated.
Step four: step five of example 1 was followed.
Comparative example 6:
the ratio of the amounts of the substances is the synthesis of the copolymer of glycolide to L-lactide to caprolactone=60 mol%:20mol% and the preparation of the monofilament absorbable suture product
Step one: 34.8g of glycolide (0.3 mol, molecular weight: 116.07 g/mol), 14.4g of lactide (0.1 mol, molecular weight: 144.13 g/mol), 11.4g of caprolactone (0.1 mol, molecular weight: 114.41 g/mol), 1.8mg of 1, 4-butanediol (0.08 mmol, molecular weight: 90.12 g/mol), 40.5mg of stannous octoate (0.4 mmol, molecular weight: 405.1 g/mol) were accurately weighed, and three ester monomers, a glycol initiator, and a catalyst were added to the three-necked flask.
Step two: repeatedly introducing nitrogen into the three-mouth bottle and extracting for 5 times, placing the three-mouth bottle into an oil bath after extracting, mechanically stirring, heating to 130 ℃ to enable the ester monomer to be completely dissolved into a clear and transparent state, heating the system to 200 ℃ to react for 2 hours, and crushing the three-mouth bottle when cooling to a room temperature state to take out a crude product.
Step three: step four of example 1 was repeated.
Step four: step five of example 1 was followed.
Comparative example 7:
the mass ratio of glycolide to L-lactide to caprolactone=60% to 20% terpolymer and suture were prepared.
Step one: 11.61g of glycolide (0.1 mol, molecular weight: 116.07 g/mol), 14.41g L-lactide (0.1 mol, molecular weight: 144.13 g/mol), 11.41g of caprolactone (0.1 mol, molecular weight: 114.14 g/mol), 1.8mg of 1, 4-butanediol (0.02 mmol, molecular weight: 90.12 g/mol), 48.8mg of zirconium acetylacetonate (0.1 mmol, molecular weight: 487.7 g/mol) and a catalyst were accurately weighed into a three-necked flask.
Step two: step two of example 1 was repeated.
Step three: heating to 170 ℃ to melt the prepolymer, adding 23.21g (0.2 mol) of melted glycolide monomer, heating to 200 ℃ to react for 2 hours after the mixture is completely melted to obtain the terpolymer, and crushing the terpolymer by a three-necked bottle when the terpolymer is cooled to a room temperature state.
Step four: step four of example 1 was repeated.
Step five: step five of example 1 was followed.
Comparative example 8:
the mass ratio of glycolide to L-lactide to caprolactone=60% to 20% terpolymer and suture were prepared.
Step one: 14.41. 14.41g L-lactide (0.1 mol, molecular weight: 144.13 g/mol), 1.8mg (0.02 mmol, molecular weight: 90.12 g/mol) of 1, 4-butanediol, 40.51mg (0.1 mmol, molecular weight: 405.1 g/mol) of stannous octoate, L-lactide, diol initiator and catalyst were accurately weighed into a three-necked flask. Repeatedly introducing nitrogen into the three-mouth bottle and extracting for 5 times, placing the three-mouth bottle into an oil bath after extracting, mechanically stirring, heating to 130 ℃ to enable the ester monomer to be completely melted to a clear and transparent state, heating the system to 200 ℃ to react for 2 hours, and crushing the three-mouth bottle to take out the L-lactide oligomer when cooling to a room temperature state.
Step two: 11.61g of glycolide (0.1 mol, molecular weight: 116.07 g/mol), 11.41g of caprolactone (0.1 mol, molecular weight: 114.14 g/mol), 1.8mg (0.02 mmol, molecular weight: 90.12 g/mol), 40.5mg of stannous octoate (0.1 mmol, molecular weight: 405.1 g/mol) were accurately weighed, and two ester monomers, a glycol initiator, and a catalyst were added to a three-necked flask. Repeatedly introducing nitrogen into the three-mouth bottle and extracting for 5 times, placing the three-mouth bottle into an oil bath after extracting, mechanically stirring, heating to 130 ℃ to enable the ester monomer to be completely melted to a clear and transparent state, heating the system to 200 ℃ to react for 2 hours, and crushing the three-mouth bottle when cooling to a room temperature state to take out the glycolide-caprolactone copolymer.
Step three: mixing the polymer obtained in the first step and the second step in a three-mouth bottle, repeatedly introducing nitrogen into the three-mouth bottle and extracting for 5 times, placing the three-mouth bottle in an oil bath after the extraction is finished, mechanically stirring while heating to 130 ℃ to enable the ester monomer to be completely melted to a clear and transparent state, heating the system to 200 ℃ to react for 2 hours, and crushing the three-mouth bottle when cooling to a room temperature state to take out the terpolymer.
Step four: step four of example 1 was repeated.
Step five: step five of example 1 was followed.
Comparative example 9:
the mass ratio of glycolide to L-lactide to caprolactone=60% to 20% terpolymer and suture were prepared.
Step one: step one of example 1 is followed.
Step two: step two of example 1 was repeated.
Step three: heating to 170 ℃ to dissolve the prepolymer, adding 23.21g (0.2 mol) of melted glycolide monomer, heating to 220 ℃ to react for 6 hours after the mixture is completely melted to obtain the terpolymer, and crushing the terpolymer by a three-necked bottle when the terpolymer is cooled to a room temperature state.
Step four: step four of example 1 was repeated.
Step five: step five of example 1 was followed.
The DSC spectrum of the terpolymer prepared in the embodiment 1 is shown in figure 3, and the terpolymer has a melting point which is not fixed due to random copolymerization, has a glass transition temperature Tg of 32.5 ℃ which is lower than the body temperature of a human body, and is easy to degrade in the human body.
The TGA spectrum of the terpolymer prepared in the embodiment 1 is shown in fig. 4, and the temperature of the terpolymer at 10% of thermal weight loss is 295 ℃, so that the terpolymer has better thermal property.
The terpolymer obtained in example 1 1 As shown in FIG. 5, the HNMR spectrum calculated according to the formants and peak areas thereof shows that the mass ratio of glycolide, lactide and caprolactone is 62mol percent to 22mol percent to 16mol percent, which is basically consistent with the feeding ratio of the first embodiment.
The terpolymers and sutures prepared in examples 1 to 3 and comparative examples 1 to 9 were subjected to performance tests, and the test results are shown in table 1 below.
Wherein the terpolymer is characterized byThe viscosity number test method comprises the following steps: a hexafluoroisopropanol solution of the copolymer was prepared at a concentration c of 0.1g/dL, and the solution time T at 25℃and the blank solvent time T were measured using a Ubbelohde viscometer 0 According to the approximation formula η=ln (T/T 0 ) And/c, calculating the intrinsic viscosity eta.
The method for testing the diameter of the suture comprises the following steps: reference is made to the method of the annex A line diameter measurement test in national standard YY 1116-2020.
The test method of the breaking strength of the suture comprises the following steps: reference is made to the test method of the breaking strength and the needle and line connection strength of annex B in national standard YY 1116-2020.
Figure BDA0003312398540000161
Figure BDA0003312398540000171
Comparing examples 1 to 3 with comparative examples 1 to 4, it is clear that when the three ester monomers are out of the range of 60 to 78mol% of glycolide, 2 to 20mol% of L-lactide and 20mol% of caprolactone, a suture with breaking strength of not less than 4N cannot be prepared, and the requirements of national standard YY1116-2020 on breaking strength of B-class (single strand) 6-0 suture cannot be met.
Comparing example 1 with comparative example 5 and comparative example 6, it can be seen that the prepared terpolymer has low intrinsic viscosity and difficult spinning by directly mixing all reactants for reaction.
Comparing example 1 with comparative example 7, it can be seen that although the suture line meeting the requirements of national standard YY1116-2020 on breaking strength of class B (single strand) 6-0 suture can be prepared by using zirconium acetylacetonate as a catalyst, zirconium element has cytotoxicity and limits the application thereof.
Comparing example 1 with comparative example 8, it can be seen that the terpolymer prepared by copolymerizing two of the ester monomers and then polymerizing the third ester monomer has low intrinsic viscosity and is difficult to spin.
Comparing example 1 with comparative example 9, it can be seen that too high a reaction temperature and too long a time can result in darkening of the terpolymer, partial degradation, and a decrease in viscosity, failing to meet the spinning requirements.
The technical features of the above-described embodiments may be arbitrarily combined, and all possible combinations of the technical features in the above-described embodiments are not described for brevity of description, however, as long as there is no contradiction between the combinations of the technical features, they should be considered as the scope of the description.
The above examples illustrate only a few embodiments of the invention, which are described in detail and are not to be construed as limiting the scope of the invention. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the invention, which are all within the scope of the invention. Accordingly, the scope of protection of the present invention is to be determined by the appended claims.

Claims (11)

1. A suture is characterized in that the suture is prepared by melt spinning of a terpolymer;
the terpolymer is prepared by copolymerizing 60-70 mol% of glycolide, 10-20 mol% of L-lactide and 20mol% of caprolactone under the catalysis of stannous octoate according to the mole percentage;
the step of copolymerizing to form the terpolymer comprises: mixing part of the glycolide, the L-lactide and the caprolactone, and heating and reacting under a negative pressure state by taking stannous octoate as a catalyst to generate a prepolymer, wherein the ratio of the mass of part of the glycolide to the mass of the caprolactone is 45:55-55:45;
adding the rest glycolide into the prepolymer, and continuing to carry out heating reaction to obtain the terpolymer;
the diameter of the suture line is 100-149 mu m.
2. The suture thread of claim 1, wherein a glycol initiator is further added during the step of forming the prepolymer.
3. The suture thread according to claim 2, wherein the ratio of the amount of ester group substance in the glycolide, the L-lactide and the caprolactone to the amount of glycol initiator substance is (10000 to 30000): 1.
4. the suture thread according to any one of claims 1 to 3, wherein a ratio of an amount of an ester group substance in the glycolide, the L-lactide, and the caprolactone to an amount of a stannous octoate substance is (2000 to 5000): 1.
5. a suture thread according to any one of claims 1 to 3 wherein the heating reaction during formation of the prepolymer comprises: firstly, heating to 120-130 ℃, keeping the temperature until the materials are melted, continuously heating to 145-170 ℃, keeping the materials capable of stirring, and reacting for 3-6 hours; and/or
The operation of the heating reaction in the formation of the terpolymer includes: and heating to 190-210 ℃, and keeping the temperature for reaction for 2-4 hours.
6. A method of making a suture, comprising the steps of:
providing a terpolymer;
melt spinning the terpolymer;
the terpolymer is prepared by copolymerizing 60-70 mol% of glycolide, 10-20 mol% of L-lactide and 20mol% of caprolactone under the catalysis of stannous octoate according to the mole percentage;
the step of copolymerizing to form the terpolymer comprises: mixing part of the glycolide, the L-lactide and the caprolactone, and heating and reacting under a negative pressure state by taking stannous octoate as a catalyst to generate a prepolymer, wherein the ratio of the mass of part of the glycolide to the mass of the caprolactone is 45:55-55:45;
adding the rest glycolide into the prepolymer, and continuing to carry out heating reaction to obtain the terpolymer;
the diameter of the suture line is 100-149 mu m.
7. The method for producing a suture thread according to claim 6, wherein the melt temperature of the melt spinning is 150 ℃ to 180 ℃.
8. The method for producing a suture thread according to claim 6, wherein the draw ratio of melt spinning is 4:1 to 9:1.
9. The method for producing a suture thread according to claim 6, wherein the drawing temperature of the melt spinning is 50 ℃ to 80 ℃.
10. Use of a suture according to any one of claims 1 to 5 or a suture prepared by a method according to any one of claims 6 to 9 in biomedical science.
11. Use of the suture according to claim 10 in biomedical non-therapeutic purposes.
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WO2009034975A1 (en) * 2007-09-14 2009-03-19 Gunze Limited GLYCOLIDE/ ε -CAPROLACTONE COPOLYMER, SUTURES MADE BY USING THE SAME, AND PROCESSES FOR PRODUCTION OF BOTH

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US4045418A (en) * 1975-01-28 1977-08-30 Gulf Oil Corporation Copolymers of D,L-lactide and epsilon caprolactone
CN1133680C (en) * 1999-04-26 2004-01-07 中国科学院化学研究所 Biodegradable three-element copolymerized ester and its processing process
KR101177656B1 (en) * 2011-09-23 2012-08-27 주식회사 메타바이오메드 Biodegradable polymer for suture and making method of it
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