CN113881021A - Terpolymer, suture line, preparation method and application thereof - Google Patents

Terpolymer, suture line, preparation method and application thereof Download PDF

Info

Publication number
CN113881021A
CN113881021A CN202111220472.4A CN202111220472A CN113881021A CN 113881021 A CN113881021 A CN 113881021A CN 202111220472 A CN202111220472 A CN 202111220472A CN 113881021 A CN113881021 A CN 113881021A
Authority
CN
China
Prior art keywords
mol
terpolymer
glycolide
caprolactone
lactide
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN202111220472.4A
Other languages
Chinese (zh)
Other versions
CN113881021B (en
Inventor
徐家林
凤鹏举
范义飞
刘逸涵
毛秦岑
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Huangpu Institute of Materials
Original Assignee
Huangpu Institute of Materials
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Huangpu Institute of Materials filed Critical Huangpu Institute of Materials
Priority to CN202111220472.4A priority Critical patent/CN113881021B/en
Publication of CN113881021A publication Critical patent/CN113881021A/en
Application granted granted Critical
Publication of CN113881021B publication Critical patent/CN113881021B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • 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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Textile Engineering (AREA)
  • Medicinal Chemistry (AREA)
  • Polymers & Plastics (AREA)
  • Materials Engineering (AREA)
  • Mechanical Engineering (AREA)
  • General Chemical & Material Sciences (AREA)
  • Surgery (AREA)
  • Vascular Medicine (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Materials For Medical Uses (AREA)
  • Polyesters Or Polycarbonates (AREA)

Abstract

The invention relates to a terpolymer which is prepared by copolymerizing 60-78 mol% of glycolide, 2-20 mol% of L-lactide and 20 mol% of caprolactone under the catalysis of stannous octoate according to the mol percentage. The glycolide, the L-lactide and the caprolactone are subjected to ring-opening polymerization to obtain the terpolymer which has good degradability and thermal properties, and further the terpolymer is subjected to melt spinning to obtain a suture with good mechanical properties, so that the terpolymer is suitable for the field of biomedicine.

Description

Terpolymer, suture line, preparation method and application thereof
Technical Field
The invention relates to the technical field of absorbable medical materials, in particular to a terpolymer and a suture as well as a preparation method and application thereof.
Background
The absorbable medical material is widely applied to the processes of suturing wounds, ligating cavity tubes, involuting tissues, fixing implants, repairing wound surfaces and the like. The chemical composition of the biodegradable carbon dioxide biodegradable polymer is mainly biodegradable polymer, and the biodegradable carbon dioxide can be finally degraded into water and carbon dioxide which are nontoxic and harmless to a human body after the mechanical strength of the biodegradable polymer is maintained for a certain time by the human body and discharged out of the human body through metabolism.
L-lactide (LLA) and Glycolide (GA) have been studied for their controlled degradation and good biocompatibility in the fields of controlled drug release, tissue scaffolds, bone fixation, etc. However, the mechanical properties of their homopolymers (polylactic acid (PLLA), polyglycolic acid (PGA)) and copolymers (PLGA) are not ideal, which affects their application in biomedical fields.
Polycaprolactone (PCL) is a flexible polymer that has been widely used in tissue engineering and drug delivery applications due to its rubbery elasticity and biocompatibility, especially PCL-based materials have a very broad application prospect in biomedical applications.
In the traditional method, poly-L-lactide oligomer is prepared into a hard phase, poly (glycolide/caprolactone) copolymer is prepared into a soft phase, and the hard phase and the soft phase are prepared into poly-L-lactide-poly (glycolide/caprolactone) multi-block copolymer by a coupling method.
Disclosure of Invention
Based on the above, there is a need for 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 20 mol% of caprolactone under the catalysis of stannous octoate according to the mol percentage.
In one embodiment, the copolymer is prepared by copolymerizing 60 mol% to 70 mol% of the glycolide, 10 mol% to 20 mol% of the L-lactide and 20 mol% of the caprolactone under catalysis of the stannous octoate in terms of mole percentage.
In one embodiment, the copolymer is prepared by copolymerizing 72 mol% to 78 mol% of the glycolide, 2 mol% to 8 mol% of the L-lactide and 20 mol% of the caprolactone under catalysis of the stannous octoate in terms of mol percentage.
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 20 mol% of caprolactone according to mol percentage;
mixing part of glycolide, L-lactide and caprolactone, heating and reacting to generate a prepolymer in a negative pressure state by taking stannous octoate as a catalyst, wherein the ratio of the amount of the part of glycolide to the amount of the caprolactone is 45: 55-45;
and adding the rest glycolide into the prepolymer, and continuing heating for reaction to obtain the terpolymer.
In one embodiment, a diol initiator is also added during the step of forming the prepolymer.
In one embodiment, the ratio of the amount of the substance of ester group in the glycolide, the L-lactide, and the caprolactone to the amount of the substance of the diol initiator is (10000 to 30000): 1.
in one embodiment, the ratio of the amount of ester group-containing substances in the glycolide, the L-lactide and the caprolactone to the amount of stannous octoate-containing substances is (2000-5000): 1.
in one embodiment, the heating reaction 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 h; and/or
In the process of forming the terpolymer, the heating reaction comprises: heating to 190-210 ℃, and keeping the temperature to react for 2-4 h.
The invention also provides a preparation method of the suture, which is to melt-spin the terpolymer described in any one of the above embodiments or the terpolymer prepared by the preparation method of the terpolymer described in any one of the above embodiments.
In one embodiment, the melt temperature of the melt spinning is 150 ℃ to 180 ℃; and/or
The draft ratio of 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 prepared by the preparation method of the suture in any embodiment.
In one embodiment, the suture has a diameter of 100 to 149 um.
The invention also provides a use of a suture according to any of the above embodiments in biomedicine.
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 property, and can be further melt-spun to obtain a suture with good mechanical property, so that the suture is suitable for the field of biomedicine.
Drawings
FIG. 1 is a pictorial representation of an embodiment of a terpolymer;
FIG. 2 is a representation of a suture thread melt spun from the terpolymer of FIG. 1;
FIG. 3 is a DSC spectrum of the terpolymer of FIG. 1;
FIG. 4 is a TGA profile of the terpolymer of FIG. 1;
FIG. 5 is a view of the terpolymer of FIG. 11HNMR spectrogram.
Detailed Description
To facilitate an understanding of the invention, the invention will now be described more fully with reference to the accompanying 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 in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed items.
One embodiment of the invention provides a terpolymer which is prepared by copolymerizing 60-78 mol% of glycolide, 2-20 mol% of L-lactide and 20 mol% of caprolactone under the catalysis of stannous octoate according to mol percentage. As shown in FIG. 1, this example provides a terpolymer 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 copolymer is prepared by copolymerizing 60 mol% to 70 mol% of glycolide, 10 mol% to 20 mol% of L-lactide and 20 mol% of caprolactone under the catalysis of stannous octoate according to mol percentage.
In a specific example, the copolymer is prepared by copolymerizing 72 mol% to 78 mol% of glycolide, 2 mol% to 8 mol% of L-lactide and 20 mol% of caprolactone under the catalysis of stannous octoate according to mol percentage.
An embodiment of the present invention further provides a method for preparing a terpolymer, including the following steps S110 to S130.
S110: weighing 60-78 mol% of glycolide, 2-20 mol% of L-lactide and 20 mol% of caprolactone according to mol percentage.
In a specific example, 60 mol% to 70 mol% glycolide, 10 mol% to 20 mol% L-lactide, and 20 mol% caprolactone are weighed in terms of mole percentage.
In a specific example, 72 mol% to 78 mol% glycolide, 2 mol% to 8 mol% L-lactide, and 20 mol% caprolactone are weighed in terms of mole percentage.
S120: mixing part of glycolide, L-lactide and caprolactone, heating and reacting to generate a prepolymer in a negative pressure state by taking stannous octoate as a catalyst, wherein the ratio of the amount of the part of glycolide to the amount of the caprolactone is 45: 55-55: 45. Stannous octoate can catalyze glycolide, L-lactide and caprolactone to carry out polymerization reaction, and the reaction rate is improved. Part of glycolide is added to generate a prepolymer, so that the glycolide can be prevented from self-polymerization, and the generation of byproducts is reduced. Preferably, the ratio of the amount of material of partial glycolide to the amount of material of caprolactone is 50: 50.
In one specific example, the ratio of the amount of the ester group in glycolide, L-lactide, and caprolactone to the amount of the stannous octoate is (2000-5000): 1. further, the ratio of the amount of ester group substances in glycolide, L-lactide and caprolactone to the amount of stannous octoate substances is (4000-5000): 1.
in one specific example, a diol-based initiator is also added in the step of forming the prepolymer. Wherein the diol initiator can initiate the polymerization reaction of ester monomers such as glycolide, L-lactide, caprolactone and the like. The diol initiator may be, but is not limited to, one or a mixture of 1, 4-butanediol, diethylene glycol, pentanediol, and lauryl alcohol.
In a specific example, the ratio of the amount of the substance of ester group to the amount of the substance of diol initiator in glycolide, L-lactide, and caprolactone is (10000 to 30000): 1. further, the ratio of the amount of the substance having an ester group in glycolide, L-lactide, and caprolactone to the amount of the substance having a diol initiator is (10000 to 25000): 1.
in one specific example, the heating reaction during the 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 h. The temperature of the materials is raised to be higher than the melting temperature of the glycolide, the L-lactide and the caprolactone during melting, and the materials are gradually raised after being completely melted, so that the phenomenon that the reactivity of the materials with high reactivity is too high, for example, the reactivity of the glycolide is high, and if the temperature raising rate is too high, the glycolide can be self-polymerized, and the number of byproducts is increased is avoided.
S130: and adding the rest glycolide into the prepolymer, and continuously heating for reaction to obtain the terpolymer.
The prepolymer and the remaining glycolide are melted separately before the remaining glycolide is added. If the prepolymer is not solidified after step S120, the prepolymer need not be subjected to a melting step, and if the prepolymer is solidified, the prepolymer is first melted. The operation of melting the prepolymer comprises: the prepolymer is heated to 170 ℃ to 190 ℃ and the temperature is maintained until the prepolymer is molten.
In one particular example, in forming the terpolymer, the act of heating the reaction comprises: heating to 190-210 ℃, and keeping the temperature to react for 2-4 h.
Further, step S140 may be further included.
S140: and purifying the terpolymer to obtain the high-purity terpolymer.
In one particular example, the operation of purifying the terpolymer comprises: adding a first organic solvent into the terpolymer to dissolve the terpolymer, filtering, settling the filtrate by using a second organic solvent, filtering again, and drying the filter residue for 24-48 h under the vacuum condition of 100-120 ℃.
The first organic solvent may be, but is not limited to, one or a mixture of hexafluoroisopropanol, trifluoroacetic acid, tetrachloroethane, and dimethyl sulfoxide.
The second organic solvent may be, but is not limited to, one or a mixture 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 any one of the specific examples is subjected to melt spinning.
In one specific example, the melt temperature of the melt spinning is 150 ℃ to 180 ℃.
In a specific example, the melt spinning draft ratio is 4:1 to 9: 1.
In one specific example, the draw down temperature for melt spinning is 50 ℃ to 80 ℃.
As shown in fig. 2, the present invention also provides a suture thread prepared by the method for preparing a suture thread according to any one of the above embodiments.
In one particular example, the suture has a diameter of 100 to 149 um. The suture line has good toughness and is not easy to break, and meets the requirement of national standard YY1116-2020 on breaking strength of B-type (single-strand) suture lines.
The invention also provides a use of a suture according to any of the above examples in biomedicine. It will be appreciated that the above sutures may be applied in biomedicine for non-therapeutic purposes.
The glycolide, the L-lactide and the caprolactone are subjected to ring-opening polymerization to obtain the high-purity terpolymer which has good degradation performance and thermal performance, and further, the terpolymer can be subjected to melt spinning to obtain a suture with good mechanical property, so that the high-purity terpolymer is suitable for the field of biomedicine.
The following are specific examples. In the following examples, all the starting materials are commercially available unless otherwise specified.
Example 1:
the amount ratio of the substances is 60 mol% of glycolide, L-lactide and caprolactone, 20 mol% of caprolactone and the preparation of the suture.
The method comprises the following steps: accurately weighed 11.61g of glycolide (0.1mol, molecular weight: 116.07g/mol), 14.41g L-lactide (0.1mol, molecular weight: 144.13g/mol), 11.41g of caprolactone (0.1mol, molecular weight: 114.14g/mol), 1.8mg of 1, 4-butanediol (0.02mmol, molecular weight: 90.12g/mol), 40.5mg of stannous octoate (0.1mmol, molecular weight: 405.1g/mol), and three ester monomers, a glycol initiator, and a catalyst were charged into a three-necked flask.
Step two: and (3) repeatedly introducing nitrogen into the three-mouth bottle and pumping out for 5 times, placing the three-mouth bottle in an oil bath after pumping, carrying out mechanical stirring, simultaneously heating to 130 ℃ to completely melt the ester monomer to a clear and transparent state, then heating the system to 145 ℃, observing an experimental state during the heating, if the viscosity of the material is too high and stirring is difficult, continuously heating until stirring can be carried out, and reacting for 6 hours to form a prepolymer.
Step three: heating to 170 ℃ to melt the prepolymer, adding 23.21g (0.2mol) of the melted glycolide monomer, heating to 200 ℃ after the mixture is completely melted to react for 2 hours to obtain the terpolymer, and crushing the three-necked bottle to take out the terpolymer after cooling to the room temperature.
Step four: smashing the terpolymer by using a grinder, adding hexafluoroisopropanol according to the ratio of the weight of the terpolymer to the volume of the first organic solvent being 1g: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 filamentous fibers, and drying the white filamentous fibers at 100 ℃ under a vacuum condition for 24 hours until the weight is constant to obtain the purified terpolymer.
Step five: and carrying out melt spinning on the purified terpolymer at the melting temperature of 170 ℃, the drafting ratio of 9:1 and the drafting temperature of 60 ℃, and carrying out heat setting to obtain the suture.
Example 2:
the amount ratio of the substances is 75 mol% of glycolide, L-lactide and caprolactone, 5 mol% and 20 mol% of the terpolymer and the preparation of the suture.
The method comprises the following steps: accurately weighed 4.64g of glycolide (0.04mol, molecular weight: 116.07g/mol), 1.44g L-lactide (0.01mol, molecular weight: 144.13g/mol), 4.58g of caprolactone (0.04mol, molecular weight: 114.14g/mol), 1.8mg of 1, 4-butanediol (0.02mmol, molecular weight: 90.12g/mol), 16.2mg of stannous octoate (0.04mmol, molecular weight: 405.1g/mol), and three ester monomers, a glycol initiator, and a catalyst were charged into a three-necked flask.
Step two: the same as step two in example 1.
Step three: heating to 170 ℃ to melt the prepolymer, adding 12.77g (0.11mol) of the melted glycolide monomer, heating to 200 ℃ after the mixture is completely melted to react for 2 hours to obtain the terpolymer, and crushing the three-necked bottle to take out the terpolymer after cooling to the room temperature.
Step four: the same procedure as in step four of example 1.
Step five: the same as step five in example 1.
Example 3:
the material amount ratio is 70 mol% of glycolide, L-lactide and caprolactone, 10 mol% and 20 mol% of terpolymer and suture.
The method comprises the following steps: accurately weighed 4.64g of glycolide (0.04mol, molecular weight: 116.07g/mol), 2.88g L-lactide (0.02mol, molecular weight: 144.13g/mol), 4.58g of caprolactone (0.04mol, molecular weight: 114.14g/mol), 1.8mg of 1, 4-butanediol (0.02mmol, molecular weight: 90.12g/mol), 16.2mg of stannous octoate (0.04mmol, molecular weight: 405.1g/mol), and three ester monomers, a glycol initiator, and a catalyst were charged into a three-necked flask.
Step two: the same as step two in example 1.
Step three: heating to 170 ℃ to melt the prepolymer, adding 11.61g (0.1mol) of the melted glycolide monomer, heating to 200 ℃ after the mixture is completely melted to react for 2 hours to obtain the terpolymer, and crushing the three-necked bottle to take out the terpolymer after cooling to the room temperature.
Step four: the same procedure as in step four of example 1.
Step five: the same as step five in example 1.
Comparative example 1:
the amount ratio of the substances is 80 mol% of glycolide, L-lactide and caprolactone, 10 mol% of caprolactone and the preparation of the suture.
The method comprises the following steps: accurately weighed 5.80g of glycolide (0.05mol, molecular weight: 116.07g/mol), 7.21g L-lactide (0.05mol, molecular weight: 144.13g/mol), 5.71g of caprolactone (0.05mol, molecular weight: 114.14g/mol), 1.8mg of 1, 4-butanediol (0.02mmol, molecular weight: 90.12g/mol), 40.5mg of stannous octoate (0.1mmol, molecular weight: 405.1g/mol), and three ester monomers, a glycol initiator, and a catalyst were added to a three-necked flask.
Step two: the same as step two in example 1.
Step three: heating to 170 ℃ to melt the prepolymer, adding 40.6g (0.35mol) of the melted glycolide monomer, heating to 200 ℃ after the mixture is completely melted to react for 2 hours to obtain the terpolymer, and crushing the three-necked bottle to take out the terpolymer after cooling to the room temperature.
Step four: the same procedure as in step four of example 1.
Step five: the same as step five in example 1.
Comparative example 2:
the amount ratio of the substances is 60 mol% of glycolide, L-lactide and caprolactone, 10 mol% and 30 mol% of the terpolymer and the preparation of the suture.
The method comprises the following steps: accurately weighed 17.41g of glycolide (0.15mol, molecular weight: 116.07g/mol), 7.21g L-lactide (0.05mol, molecular weight: 144.13g/mol), 17.12g of caprolactone (0.15mol, molecular weight: 114.14g/mol), 1.8mg of 1, 4-butanediol (0.02mmol, molecular weight: 90.12g/mol), 40.5mg of stannous octoate (0.1mmol, molecular weight: 405.1g/mol), and three ester monomers, a glycol initiator, and a catalyst were added to a three-necked flask.
Step two: the same as step two in example 1.
Step three: heating to 170 ℃ to melt the prepolymer, adding 17.41g (0.15mol) of the melted glycolide monomer, heating to 200 ℃ after the mixture is completely melted to react for 2 hours to obtain the terpolymer, and crushing the three-necked bottle to take out the terpolymer after cooling to the room temperature.
Step four: the same procedure as in step four of example 1.
Step five: the same as step five in example 1.
Comparative example 3:
the amount ratio of the substances is 90 mol% of glycolide, L-lactide and caprolactone, 10 mol% of caprolactone and the preparation of the suture.
The method comprises the following steps: accurately weighed 5.8g of glycolide (0.05mol, molecular weight: 116.07g/mol), 7.21g L-lactide (0.05mol, molecular weight: 144.13g/mol), 5.71g of caprolactone (0.05mol, molecular weight: 114.14g/mol), 1.8mg of 1, 4-butanediol (0.02mmol, molecular weight: 90.12g/mol), 40.5mg of stannous octoate (0.1mmol, molecular weight: 405.1g/mol), and three ester monomers, a glycol initiator, and a catalyst were added to a three-necked flask.
Step two: the same as step two in example 1.
Step three: heating to 170 ℃ to melt the prepolymer, adding 46.42g (0.4mol) of the melted glycolide monomer, heating to 200 ℃ after the mixture is completely melted to react for 2 hours to obtain the terpolymer, and crushing the three-necked bottle to take out the terpolymer after cooling to the room temperature.
Step four: the same procedure as in step four of example 1.
Step five: the same as step five in example 1.
Comparative example 4:
the amounts of the materials are 99.8 mol% of glycolide, 0.1 mol% of L-lactide and 0.1 mol% of caprolactone, and the preparation of the suture.
The method comprises the following steps: accurately weighed 0.12g of glycolide (0.001mol, molecular weight: 116.07g/mol), 0.14g L-lactide (0.001mol, molecular weight: 144.13g/mol), 0.14g of caprolactone (0.001mol, molecular weight: 114.14g/mol), 1.8mg of 1, 4-butanediol (0.02mmol, molecular weight: 90.12g/mol), 40.5mg of stannous octoate (0.1mmol, molecular weight: 405.1g/mol), and three ester monomers, a glycol initiator, and a catalyst were added to a three-necked flask.
Step two: the same as step two in example 1.
Step three: heating to 170 ℃ to melt the prepolymer, adding 115.7g (0.997mol) of the melted glycolide monomer, heating to 200 ℃ after the mixture is completely melted to react for 2 hours to obtain the terpolymer, and crushing the three-necked bottle to take out the terpolymer after cooling to the room temperature.
Step four: the same procedure as in step four of example 1.
Step five: the same as step five in example 1.
Comparative example 5:
the amounts of the materials are 33.3 mol% of glycolide, 33.3 mol% of L-lactide and caprolactone, 33.3 mol% of caprolactone and 33.4 mol% of the preparation of the terpolymer and the suture.
The method comprises the following steps: accurately weighed 11.6g of glycolide (0.1mol, molecular weight: 116.07g/mol), 14.4g L-lactide (0.1mol, molecular weight: 144.13g/mol), 11.4g of caprolactone (0.1mol, molecular weight: 114.14g/mol), 1.8mg of 1, 4-butanediol (0.02mmol, molecular weight: 90.12g/mol), 40.5mg of stannous octoate (0.1mmol, molecular weight: 405.1g/mol), and three ester monomers, a glycol initiator, and a catalyst were added to a three-necked flask.
Step two: and (3) repeatedly introducing nitrogen into the three-mouth bottle and pumping out for 5 times, placing the three-mouth bottle in an oil bath after the pumping is finished, carrying out mechanical stirring and simultaneously heating to 130 ℃ to completely melt the ester monomer to a clear and transparent state, then heating the system to 200 ℃ to react for 2 hours, and crushing the three-mouth bottle to obtain the terpolymer when the system is cooled to the room temperature state.
Step three: the same procedure as in step four of example 1.
Step four: the same as step five in example 1.
Comparative example 6:
synthesis of copolymer with the mass ratio of glycolide to L-lactide to caprolactone being 60 mol% to 20 mol% and preparation of monofilament absorbable suture line product
The method comprises the following steps: 34.8g of glycolide (0.3mol, molecular weight: 116.07g/mol), 14.4g of lactide (0.1mol, molecular weight: 144.13g/mol), 11.4g of caprolactone (0.1mol, molecular weight: 114.41g/mol), 1.8mg of 1, 4-butanediol (0.08mmol, molecular weight: 90.12g/mol), 40.5mg of stannous octoate (0.4mmol, molecular weight: 405.1g/mol) were accurately weighed, and the three ester monomers, the diol initiator, and the catalyst were charged into a three-necked flask.
Step two: and (3) repeatedly introducing nitrogen into the three-mouth bottle and pumping out for 5 times, placing the three-mouth bottle in an oil bath after the pumping is finished, carrying out mechanical stirring and simultaneously heating to 130 ℃ to completely dissolve the ester monomer to a clear and transparent state, then heating the system to 200 ℃ to react for 2 hours, and crushing the three-mouth bottle when the system is cooled to the room temperature state to take out a crude product.
Step three: the same procedure as in step four of example 1.
Step four: the same as step five in example 1.
Comparative example 7:
the amount ratio of the substances is 60 mol% of glycolide, L-lactide and caprolactone, 20 mol% of caprolactone and the preparation of the suture.
The method comprises the following steps: accurately weighed 11.61g of glycolide (0.1mol, molecular weight: 116.07g/mol), 14.41g L-lactide (0.1mol, molecular weight: 144.13g/mol), 11.41g of caprolactone (0.1mol, molecular weight: 114.14g/mol), 1.8mg (0.02mmol, molecular weight: 90.12g/mol) of 1, 4-butanediol, 48.8mg of zirconium acetylacetonate (0.1mmol, molecular weight: 487.7g/mol), and three ester monomers, a diol initiator, and a catalyst were charged into a three-necked flask.
Step two: the same as step two in example 1.
Step three: heating to 170 ℃ to melt the prepolymer, adding 23.21g (0.2mol) of the melted glycolide monomer, heating to 200 ℃ after the mixture is completely melted to react for 2 hours to obtain the terpolymer, and crushing the three-necked bottle to take out the terpolymer after cooling to the room temperature.
Step four: the same procedure as in step four of example 1.
Step five: the same as step five in example 1.
Comparative example 8:
the amount ratio of the substances is 60 mol% of glycolide, L-lactide and caprolactone, 20 mol% of caprolactone and the preparation of the suture.
The method comprises the following steps: 14.41g L-lactide (0.1mol, molecular weight: 144.13g/mol), 1.8mg (0.02mmol, molecular weight: 90.12g/mol) of 1, 4-butanediol, 40.51mg of stannous octoate (0.1mmol, molecular weight: 405.1g/mol) were accurately weighed, and L-lactide, a glycol initiator, and a catalyst were added to a three-necked flask. And repeatedly introducing nitrogen into the three-mouth bottle and pumping out for 5 times, placing the three-mouth bottle in an oil bath after the pumping is finished, carrying out mechanical stirring and simultaneously heating to 130 ℃ to completely melt the ester monomer to a clear and transparent state, then heating the system to 200 ℃ to react for 2 hours, and crushing the three-mouth bottle when the system is cooled to the room temperature state and taking out the L-lactide oligomer.
Step two: accurately weighed 11.61g of glycolide (0.1mol, molecular weight: 116.07g/mol), 11.41g of caprolactone (0.1mol, molecular weight: 114.14g/mol), 1.8mg of 1, 4-butanediol (0.02mmol, molecular weight: 90.12g/mol), 40.5mg of stannous octoate (0.1mmol, molecular weight: 405.1g/mol), and two ester monomers, a glycol initiator, and a catalyst were added to a three-necked flask. And repeatedly introducing nitrogen into the three-neck flask and pumping out for 5 times, placing the three-neck flask in an oil bath after the pumping is finished, carrying out mechanical stirring and simultaneously heating to 130 ℃ to completely melt the ester monomer to a clear and transparent state, then heating the system to 200 ℃ to react for 2 hours, and crushing the three-neck flask when the system is cooled to the room temperature state to take out the glycolide-caprolactone copolymer.
Step three: mixing the polymers obtained in the first step and the second step in a three-mouth bottle, repeatedly introducing nitrogen into the three-mouth bottle and pumping out for 5 times, placing the three-mouth bottle in an oil bath after pumping, carrying out mechanical stirring and simultaneously heating to 130 ℃ to completely melt the ester monomers to a clear and transparent state, then heating the system to 200 ℃ for reaction for 2 hours, and crushing the three-mouth bottle and taking out the terpolymer after cooling to a room temperature state.
Step four: the same procedure as in step four of example 1.
Step five: the same as step five in example 1.
Comparative example 9:
the amount ratio of the substances is 60 mol% of glycolide, L-lactide and caprolactone, 20 mol% of caprolactone and the preparation of the suture.
The method comprises the following steps: the same procedure as in example 1.
Step two: the same as step two in example 1.
Step three: heating to 170 ℃ to dissolve the prepolymer, adding 23.21g (0.2mol) of the melted glycolide monomer, heating to 220 ℃ after the mixture is completely melted to react for 6 hours to obtain the terpolymer, and crushing the three-necked bottle to take out the terpolymer after cooling to the room temperature.
Step four: the same procedure as in step four of example 1.
Step five: the same as step five in example 1.
The DSC spectrogram of the terpolymer prepared in the embodiment 1 is shown in figure 3, the terpolymer has no fixed melting point due to the random copolymerization reaction, the glass transition temperature Tg of the terpolymer is 32.5 ℃, the temperature of the terpolymer is lower than the body temperature of a human body, and the terpolymer is easy to degrade in the human body.
The TGA spectrum of the terpolymer prepared in the embodiment 1 is shown in figure 4, and the temperature of the terpolymer with 10% of thermal weight loss is 295 ℃, so that the terpolymer has better thermal property.
Process for preparing terpolymer of example 11The HNMR spectrum is shown in FIG. 5, and the calculated ratio of the amounts of glycolide, lactide and caprolactone is 62 mol%: 22 mol%: 16 mol% according to the resonance peak and the peak area, which substantially matches the charge ratio of the first example.
The terpolymers and suture prepared in examples 1 to 3 and comparative examples 1 to 9 were subjected to the performance test, and the test results are shown in the following table 1.
The method for testing the intrinsic viscosity of the terpolymer comprises the following steps: preparing hexafluoroisopropanol solution of copolymer with concentration c of 0.1g/dL, and testing solution time T and blank solvent time T at 25 ℃ by using Ubbelohde viscometer0According 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: refer to the measurement test method of the line diameter in appendix A of national standard YY 1116-2020.
The method for testing the fracture strength of the suture comprises the following steps: refer to the test method of appendix B breaking strength and needle and thread connecting strength in national standard YY 1116-2020.
Figure BDA0003312398540000161
Figure BDA0003312398540000171
Comparing examples 1-3 with comparative examples 1-4, it can be seen that when the three ester monomers are in the ranges of 60 mol% -78 mol% of glycolide, 2 mol% -20 mol% of L-lactide and 20 mol% of caprolactone by mole percentage, the suture with breaking strength of 4N or more cannot be prepared, and the requirement of national standard YY1116-2020 on the breaking strength of B-type (single strand) 6-0 suture is not met.
Comparing example 1 with comparative examples 5 and 6, it can be seen that the terpolymer prepared by directly mixing all reactants for reaction has low intrinsic viscosity and is difficult to spin.
Comparing example 1 with comparative example 7, it can be seen that although sutures meeting the breaking strength requirement of national standard YY1116-2020 for class B (single strand) 6-0 sutures can also be prepared using zirconium acetylacetonate as catalyst, the zirconium element is cytotoxic, limiting its application.
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 copolymerized monomers with 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 reaction temperature and too long reaction time can result in deepening the color of the terpolymer, partial degradation, and reduced viscosity, which can not meet the spinning requirement.
The technical features of the embodiments described above may be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the embodiments described above are not described, but should be considered as being within the scope of the present specification as long as there is no contradiction between the combinations of the technical features.
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.

Claims (14)

1. The terpolymer is characterized by being prepared by copolymerizing 60-78 mol% of glycolide, 2-20 mol% of L-lactide and 20 mol% of caprolactone under the catalysis of stannous octoate according to the mol percentage.
2. The terpolymer according to claim 1, wherein the copolymer is produced by copolymerizing 60 mol% to 70 mol% of the glycolide, 10 mol% to 20 mol% of the L-lactide, and 20 mol% of the caprolactone under catalysis of the stannous octoate in terms of mole percentage.
3. The terpolymer according to claim 1, wherein the copolymer is produced by copolymerizing 72 mol% to 78 mol% of the glycolide, 2 mol% to 8 mol% of the L-lactide, and 20 mol% of the caprolactone under catalysis of the stannous octoate in terms of mol percentage.
4. A method for preparing a terpolymer, comprising the steps of:
weighing 60-78 mol% of glycolide, 2-20 mol% of L-lactide and 20 mol% of caprolactone according to mol percentage;
mixing part of glycolide, L-lactide and caprolactone, heating and reacting to generate a prepolymer in a negative pressure state by taking stannous octoate as a catalyst, wherein the ratio of the amount of the part of glycolide to the amount of the caprolactone is 45: 55-55: 45;
and adding the rest glycolide into the prepolymer, and continuing heating for reaction to obtain the terpolymer.
5. The method of producing a terpolymer according to claim 4, wherein a diol initiator is further added in the step of forming the prepolymer.
6. The method according to claim 5, wherein the ratio of the amount of the ester group-containing substance in the glycolide, the L-lactide, and the caprolactone to the amount of the diol initiator is (10000 to 30000): 1.
7. the method for preparing the terpolymer according to any one of claims 4-6, wherein the ratio of the amount of the substance of ester group in the glycolide, the L-lactide and the caprolactone to the amount of the substance of the stannous octoate is (2000-5000): 1.
8. the method of producing the terpolymer according to any one of claims 4 to 6, wherein the heating reaction in the 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 h; and/or
In the process of forming the terpolymer, the heating reaction comprises: heating to 190-210 ℃, and keeping the temperature to react for 2-4 h.
9. A method for producing a suture, characterized by melt-spinning the terpolymer according to any one of claims 1 to 3 or the terpolymer produced by the method for producing a terpolymer according to any one of claims 4 to 8.
10. The method of claim 9, wherein the melt spinning has a melt temperature of 150 ℃ to 180 ℃; and/or
The draft ratio of melt spinning is 4: 1-9: 1; and/or
The drafting temperature of the melt spinning is 50-80 ℃.
11. A suture thread produced by the method for producing a suture thread according to any one of claims 9 to 10.
12. The suture of claim 11, wherein the suture has a diameter of 100 to 149 um.
13. Use of a suture according to any of claims 11 to 12 in biomedicine.
14. Use of the suture of claim 13 in biomedicine for non-therapeutic purposes.
CN202111220472.4A 2021-10-20 2021-10-20 Terpolymer, suture and preparation method and application thereof Active CN113881021B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202111220472.4A CN113881021B (en) 2021-10-20 2021-10-20 Terpolymer, suture and preparation method and application thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202111220472.4A CN113881021B (en) 2021-10-20 2021-10-20 Terpolymer, suture and preparation method and application thereof

Publications (2)

Publication Number Publication Date
CN113881021A true CN113881021A (en) 2022-01-04
CN113881021B CN113881021B (en) 2023-05-02

Family

ID=79003981

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202111220472.4A Active CN113881021B (en) 2021-10-20 2021-10-20 Terpolymer, suture and preparation method and application thereof

Country Status (1)

Country Link
CN (1) CN113881021B (en)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4045418A (en) * 1975-01-28 1977-08-30 Gulf Oil Corporation Copolymers of D,L-lactide and epsilon caprolactone
CN1271742A (en) * 1999-04-26 2000-11-01 中国科学院化学研究所 Biodegradable three-element copolymerized ester and its processing process
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
WO2013042870A1 (en) * 2011-09-23 2013-03-28 주식회사 메타바이오메드 Biodegradable polymer for a suture and method for manufacturing same
CN103992465A (en) * 2014-05-04 2014-08-20 电子科技大学 Biodegradable ternary copolymer

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4045418A (en) * 1975-01-28 1977-08-30 Gulf Oil Corporation Copolymers of D,L-lactide and epsilon caprolactone
CN1271742A (en) * 1999-04-26 2000-11-01 中国科学院化学研究所 Biodegradable three-element copolymerized ester and its processing process
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
WO2013042870A1 (en) * 2011-09-23 2013-03-28 주식회사 메타바이오메드 Biodegradable polymer for a suture and method for manufacturing same
CN103992465A (en) * 2014-05-04 2014-08-20 电子科技大学 Biodegradable ternary copolymer

Also Published As

Publication number Publication date
CN113881021B (en) 2023-05-02

Similar Documents

Publication Publication Date Title
US8309137B2 (en) DL-lactide-ε-caprolactone copolymers
JPH06122Y2 (en) Synthetic copolymer surgical suture
US8674033B2 (en) Biodegradable phase separated segmented multi block co-polymers
JP3218055B2 (en) Bioabsorbable segmented copolymer
EP0108912B1 (en) Poly(glycolic acid)/poly(alkylene glycol)block copolymers and method of manufacturing the same
JP3218148B2 (en) Copolymer of aromatic anhydride and aliphatic ester
EP2285863B1 (en) Absorbable copolyesters of poly(ethoxyethylene diglycolate) and glycolide
US6503991B2 (en) Copolyesters with minimized hydrolytic instability and crystalline absorbable copolymers thereof
JPH107772A (en) 6,6-dialkyl-1,4-dioxepan-2-one, and absorbent copolymer and blend produced from cyclic dimer or the same
US20040082755A1 (en) Monomer addition techniques to control manufacturing of bioabsorbable copolymers
US9446165B2 (en) Swellable fiber and microfiber forming polyether-esters and applications thereof
Lee et al. Synthesis and Properties of ABA Block Copoly (ester-ethers) Comprising Poly (L-lactide)(A) and Poly (oxypropylene-co-oxyethylene)(B) with Different Molecular Weights.
JPH082955B2 (en) Block copolymer and method for producing the same
CN113881021B (en) Terpolymer, suture and preparation method and application thereof
US8298260B2 (en) Compliant, long-lasting absorbable monofilament sutures
KR100348717B1 (en) Star-Shaped Glycolide/ε-Caprolactone Copolymers and Process for Their Preparation
CN116003745A (en) Polyglycolic acid resin for high molecular weight non-woven fabrics, preparation method and application thereof

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant