CN109988292B - Preparation method of degradable aliphatic copolyester - Google Patents

Preparation method of degradable aliphatic copolyester Download PDF

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CN109988292B
CN109988292B CN201910245271.6A CN201910245271A CN109988292B CN 109988292 B CN109988292 B CN 109988292B CN 201910245271 A CN201910245271 A CN 201910245271A CN 109988292 B CN109988292 B CN 109988292B
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copolyester
diol
degradable aliphatic
aliphatic copolyester
aliphatic
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CN109988292A (en
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屠迎锋
万雪婷
徐思源
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Suzhou University
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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
    • C08G63/12—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds derived from polycarboxylic acids and polyhydroxy compounds
    • C08G63/16—Dicarboxylic acids and dihydroxy compounds
    • 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
    • C08G63/66—Polyesters containing oxygen in the form of ether groups
    • C08G63/668—Polyesters containing oxygen in the form of ether groups derived from polycarboxylic acids and polyhydroxy compounds
    • C08G63/672—Dicarboxylic acids and dihydroxy compounds
    • 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
    • C08G63/68—Polyesters containing atoms other than carbon, hydrogen and oxygen
    • C08G63/682—Polyesters containing atoms other than carbon, hydrogen and oxygen containing halogens
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Abstract

The invention discloses a preparation method of degradable aliphatic copolyester, which comprises the steps of taking aliphatic macrolide as a monomer and diol as an initiator, and preparing the degradable aliphatic copolyester by in-situ ring-opening-condensation cascade polymerization reaction in the presence of a catalyst; the diol is a small molecule diol or a large molecule diol. The copolyester disclosed by the invention has higher molecular weight and higher content of functional groups, and the content of the functional groups in the copolyester can reach 75% by mass; the copolyester has degradability, and the degradation speed is controlled by conditions of temperature, enzyme and the like.

Description

Preparation method of degradable aliphatic copolyester
Technical Field
The invention belongs to the field of preparation of high polymer materials, and particularly relates to preparation of degradable aliphatic copolyester.
Background
At present, polymer materials synthesized based on olefin have the characteristics of stable property and difficult degradation in nature, and cause serious 'white pollution' problem. With the increasing attention on environmental issues and health conditions, environmentally friendly materials have been rapidly developed in recent years. Among these materials, aliphatic polyesters have many unique advantages, such as being prepared from renewable bio-based derivatives, being recyclable, and having biocompatibility, biodegradability, etc. In addition, the amphiphilic aliphatic polyester-based block copolymer can be self-assembled in water to form micelles, and drugs which are difficult to dissolve in water can be entrapped in the micelles, and the amphiphilic aliphatic polyester-based block copolymer has the characteristics of good biocompatibility, biodegradability and the like, so that the amphiphilic polyester-based block copolymer has wide application prospects in the fields of medical drug loading, controlled release and the like. However, the existing synthetic aliphatic polyester has the problems of low polymer molecular weight, difficult functionalization, low biological activity and the like.
Currently, aliphatic polyesters mainly include polylactic acid, polycaprolactone, and aliphatic polydiol esters (e.g., polyethylene glycol adipate). The former two are synthesized by ring-opening polymerization method, but it is difficult to prepare copolyester with higher molecular weight and higher content of functional group. Generally, if a high molecular weight copolyester is desired, the ratio of the monomer to the initiator is increased, but the decrease of the relative dosage of the initiator results in the decrease of the content of the functional group in the copolyester, and here, the requirement of high molecular weight and the requirement of high content of the functional group are a pair of spearheads. In addition, the ring-opening polymerization method generally obtains di-and tri-block copolymers, and is difficult to form multi-block copolymers; the aliphatic diacid diol ester is synthesized by condensation polymerization of aliphatic diacid and diol, so that side reactions are more in the polymerization process, and high-molecular-weight polyester is not easy to obtain.
At present, an effective method for introducing functional groups with higher content into degradable copolyester is lacked, and researches on synthesis and performance of degradable aliphatic copolyester are very few. In order to adapt to the development step of society, a universal method is urgently needed to be developed, functional groups are introduced into environment-friendly degradable copolyester, the functionalized aliphatic copolyester and the aliphatic multi-block copolyester can be prepared, and the method is simple and easy to implement and low in cost.
Disclosure of Invention
The invention aims to provide degradable aliphatic copolyester and a preparation method thereof. The degradable aliphatic copolyester based on poly (1, 13-ethylene tridecanedioate) (PEB) is synthesized by adopting aliphatic macrolide musk T (1, 13-ethylene tridecanedioate) as a monomer and diol as an initiator through in-situ ring-opening-condensation cascade polymerization in the presence of a catalyst. The invention adopts a new polymerization method, namely an in-situ ring-opening condensation cascade polymerization method, and carries out the ring-opening polymerization reaction and the condensation polymerization reaction in the same system in a cascade way to synthesize the aliphatic copolyester.
In order to achieve the purpose and the effect, the invention is realized by the following technical scheme:
a preparation method of degradable aliphatic copolyester comprises the following steps of taking aliphatic macrolide as a monomer and diol as an initiator, and preparing the degradable aliphatic copolyester by in-situ ring-opening-condensation cascade polymerization reaction in the presence of a catalyst.
In the invention, the aliphatic macrolide is musk T; according to the invention, macrolide which is different from micromolecule cyclic ester in the prior art is used as a monomer for the first time, and the degradable aliphatic copolyester or the degradable aliphatic polyester block copolymer is prepared through cascade polymerization, so that the molecular weight and the content of functional groups are substantially improved.
In the invention, the diol is a micromolecular diol or a macrodiol, preferably, the molecular weight of the micromolecular diol is 30-400 g per mole; the macrodiol contains a polymer segment, preferably a polyester segment or a polyether segment. The chemical formula of the diol is HOROH, when R is alkyl or fluorocarbon chain group, the diol is small molecular alcohol, preferably decanediol, 2,3,3,4, 4-hexafluoro-1, 5-pentanediol and the like; when R is a polymer segment, the diol is a macroalcohol, preferably a polyester diol or polyether diol.
In the invention, the catalyst is a titanate compound; preferably n-butyl titanate; according to the mass ratio, the feeding ratio of the monomer to the initiator can be adjusted as required, generally in the range of 1-100, and the amount of the catalyst is 0.03-2.00% of the total feeding amount of the monomer and the initiator. In the invention, the temperature of the in-situ ring-opening condensation cascade polymerization reaction is 180-260 ℃; the polymerization reaction time is 10-240 minutes; the in-situ ring-opening-condensation cascade polymerization reaction is carried out in a nitrogen atmosphere or under a vacuum condition; after the reaction is finished, the product of the degradable aliphatic copolyester can be obtained without purification.
The chemical structural formula of the degradable aliphatic copolyester disclosed by the invention is as follows:
Figure 100002_DEST_PATH_IMAGE001
wherein R is derived from an initiator, x is 10-250, and y is 2-100.
The degradable aliphatic copolyester is degradable copolyester based on aliphatic polyester, and the preparation method can be as follows:
at room temperature, adding musk T serving as a monomer and diol serving as an initiator into a reaction device, introducing nitrogen, mechanically stirring, heating to 180-260 ℃, adding a catalyst after reactants are uniformly mixed, continuously introducing nitrogen or vacuumizing, and polymerizing for 30-240 minutes to obtain the degradable aliphatic copolyester based on poly (1, 13-ethylene glycol tridecanedioate) (PEB). Or at room temperature, adding musk T serving as a monomer and diol serving as an initiator into a reaction device, then adding a catalyst, heating to 180-260 ℃, mechanically stirring, introducing nitrogen or vacuumizing, and polymerizing for 10-180 minutes to obtain the degradable aliphatic copolyester based on poly (1, 13-ethylene tridecanedioate) (PEB).
The aliphatic macrolide monomer adopted in the invention is musk T, namely 1, 13-tridecanedioic acid glycol lactone, can be conveniently obtained on the market, is low in price, and can be polymerized to obtain copolyester based on poly (1, 13-tridecanedioic acid glycol ester) (PEB); the diol initiator is a small-molecule diol or a macrodiol initiator, wherein the small-molecule diol is preferably a diol initiator containing a functional group, such as decanediol containing an alkyl chain, 2,3,3,4, 4-hexafluoro-1, 5-pentanediol containing a fluorocarbon chain and the like, and the macrodiol initiator is preferably a polyether diol or a polyester diol with a hydroxyl group at the end, such as polyethylene adipate diolEster diol (PEA), polyethylene glycol (PEO), polytetrahydrofuran diol (PTMO), or polyethylene glycol-block-polypropylene glycol-block-polyethylene glycol triblock copolymer diol (PEO-b-PPO-bPEO), and the like. The copolyester obtained by polymerization has the following structure:
Figure 142659DEST_PATH_IMAGE002
in the invention, the polymerization mechanism is an in-situ ring-opening-condensation cascade polymerization process, namely, a diol initiator firstly carries out ring-opening polymerization on musk T to obtain copolyester with a hydroxyl end group, and the copolyester can continuously initiate ring-opening polymerization of the musk T and also can carry out condensation polymerization with each other to generate copolyester with higher molecular weight; the reaction product is the degradable aliphatic copolyester, and purification and separation are not needed.
The molecular weight of the degradable aliphatic copolyester can be controlled by polymerization time and polymerization temperature, the molecular weight can reach 70.0 kg per mole, and the mass content of the functional group in the copolyester can reach 75 percent, so that the problems that the molecular weight of the polyester serving as a biological material is low and the functional group is difficult to introduce in the prior art are effectively solved.
The copolyester of the invention has degradability, and the degradation speed is controlled by conditions of temperature, enzyme and the like. The mass and the molecular weight of the compound slowly decrease with time in phosphate buffer solution (pH 7.2-7.4) at normal temperature or 37 ℃, the mass and the molecular weight of the compound rapidly decrease in phosphate buffer solution (pH 7.2-7.4) containing lipase at normal temperature or 37 ℃, and the mass and the molecular weight of the compound are basically unchanged under the refrigeration condition of 4 ℃.
The in-situ ring-opening condensation cascade polymerization method provided by the invention aims to carry out ring-opening polymerization reaction and condensation polymerization reaction in the same system in a cascade manner, so as to prepare aliphatic polyester with higher functional group content and higher molecular weight, and also can prepare multi-block copolymer with higher molecular weight and containing aliphatic polyester. The aliphatic polyester/copolyester prepared by ring-opening polymerization of cyclic ester in the prior art cannot realize high molecular weight and simultaneously has high content of functional groups. The method has the advantages of simple reaction steps, high and controllable molecular weight, no need of post-treatment, capability of large-scale synthesis and the like. The aliphatic polyester/copolyester prepared by the invention has degradability, and the degradation can be adjusted by temperature, enzyme content and the like, and the technical effects are shown in the examples. Thus, the invention discloses a preparation method of the degradable aliphatic copolyester.
The invention synthesizes the copolyester based on poly (1, 13-ethylene glycol tridecanedioate) by an in-situ ring-opening condensation cascade polymerization method, solves the problems that the traditional polymerization method is difficult to synthesize high molecular weight polyester with high functional group content and synthesize multi-block aliphatic copolyester, and has the advantages of simple reaction steps, high and controllable molecular weight, no need of post-treatment, large-scale synthesis and the like; the adopted musk T monomer can be purchased in large quantity, and the price is very cheap, so that the cost of the synthesized copolyester is very low; functional aliphatic copolyester can be conveniently prepared by introducing functional groups into diol; when polyether glycol or polyester glycol is used as a macroinitiator, the multi-block copolyester can be conveniently synthesized; the synthesized copolyester is a bio-based polyester material, has degradable performance, is a green environment-friendly material and has a great application value.
The above description is only an overview of the present invention. In order to make the technical means of the present invention more clearly understood and to make the same practical in accordance with the contents of the specification, the following is a detailed description of the embodiments of the present invention with reference to the accompanying drawings.
Drawings
FIG. 1 is a synthesis scheme of the degradable aliphatic copolyester of the present invention;
FIG. 2 is a volume exclusion chromatogram of a copolyester (PEBDB) obtained by mixing decanediol and musk T for in-situ ring-opening-condensation cascade polymerization and reacting at 200 ℃ for different times under nitrogen;
FIG. 3 is a graph showing the change of the molecular weight of a copolyester (PEBDB) obtained by mixing decamethylene glycol and musk T and carrying out in-situ ring-opening condensation cascade polymerization and reacting at 200 ℃ for different times under nitrogen with time;
FIG. 4 is a graph showing the change of the molecular weight of a copolyester (PEBDB) obtained by mixing decamethylene glycol and musk T and carrying out in-situ ring-opening condensation cascade polymerization at 240 ℃ under nitrogen for different times with time;
FIG. 5 is a volume exclusion chromatogram of a copolyester (PEBDB) obtained by mixing decanediol and musk T for in-situ ring-opening-condensation cascade polymerization and reacting at 200 ℃ for 30 minutes under vacuum;
FIG. 6 is a graph of the molecular weight of a copolyester (PEBFB) prepared by mixing 2,2,3,3,4, 4-hexafluoro-1, 5-pentanediol and musk T and reacting at 220 deg.C for various times under nitrogen as a function of time in an in-situ ring-opening condensation cascade polymerization;
FIG. 7 shows a multi-block copolyester (PEB-b-PEA-b-PEB)nA plot of molecular weight versus time of (a);
FIG. 8 shows multi-block copolyester (PEB-b-PEO-b-PEB)nVolume exclusion chromatograms of (1);
FIG. 9 shows a multi-block copolyester (PEB-b-PTMO-b-PEB)nVolume exclusion chromatograms of (1);
FIG. 10 shows a triblock copolymer of polyethylene glycol-block-polypropylene glycol-block-polyethylene glycol (PEO-b-PPO-bPEO) and musk T are mixed to carry out in-situ ring-opening condensation cascade polymerization, and the mixture reacts at 220 ℃ under nitrogen for different time to obtain multi-block copolyester (PEB-b-PEO-b-PPO-b-PEO-b-PEB)nA plot of molecular weight versus time of (a);
FIG. 11 shows a triblock copolymer of polyethylene glycol-block-polypropylene glycol-block-polyethylene glycol (PEO-b-PPO-bPEO) and musk T for in situ ring openingCondensation cascade polymerization, multiblock copolyesters obtained by reaction at 220 ℃ for 45 minutes under vacuum (PEB-b-PEO-b-PPO-b-PEO-b-PEB)nVolume exclusion chromatograms of (1);
FIG. 12 is an aliphatic multi-block copolyester (PEB-b-PEO-b-PPO-b-PEO-b-PEB)nA degradation profile of mass in phosphate buffered saline without lipase and with lipase at 37 degrees celsius as a function of time;
FIG. 13 shows aliphatic multi-block copolyester (PEB-b-PEO-b-PPO-b-PEO-b-PEB)nA degradation profile of molecular weight in phosphate buffered saline without lipase and with lipase at 20 degrees celsius as a function of time;
FIG. 14 is an aliphatic multi-block copolyester (PEB-b-PEO-b-PPO-b-PEO-b-PEB)nDegradation profile of molecular weight as a function of time in phosphate buffered saline without lipase and with lipase at 37 degrees celsius.
Detailed Description
The invention will be described in detail below with reference to the accompanying drawings and examples.
Referring to fig. 1, the preparation method of the degradable aliphatic copolyester of the present invention is shown, that is, the copolyester is prepared by an in-situ ring-opening-condensation cascade polymerization method, and comprises two processes, 1) the diol performs a ring-opening polymerization reaction on a macrolide monomer musk T to generate the copolyester diol, 2) the copolyester diol can continue to perform a ring-opening polymerization reaction on musk T, and also can perform condensation polymerization with each other to obtain a series of aliphatic copolyesters based on poly (1, 13-ethylene tridecanedioate).
EXAMPLE 1 in situ Ring opening-condensation Cascade polymerization of decamethylene glycol and Musk T mixtures to degradable aliphatic copolyesters (PEBDB)
Decamethylene glycol (0.05 g) and musk T (5.00 g) were added into a 100 ml three-neck flask, nitrogen was introduced to remove oxygen, the three-neck flask was placed in a salt bath pan and heated to 200 ℃ and mechanically stirred, then 10.1. mu.l of n-butyl titanate was slowly added through a microsyringe, and in-situ ring-opening-condensation cascade polymerization was carried out under nitrogen atmosphere to give the corresponding polymer. Samples were taken every 30 minutes during the reaction and the reaction was stopped after 120 minutes.
The volume exclusion chromatogram and the time-dependent change of the molecular weight of the copolyester are shown in fig. 2 and fig. 3, which prove the successful synthesis of the target product, and the molecular weight can be controlled by controlling the polymerization time. The functional group is calculated to be present in the copolyester in an amount of about 1% by weight.
EXAMPLE 2 in situ Ring opening-condensation Cascade polymerization of decamethylene glycol and Musk T mixtures to degradable aliphatic copolyesters (PEBDB)
Decamethylene glycol (0.50 g) and musk T (5.00 g) were added into a 100 ml three-neck flask, nitrogen was introduced to remove oxygen, the three-neck flask was placed in a salt bath pan and heated to 240 ℃ with mechanical stirring, then 11.0. mu.l of n-butyl titanate was slowly added through a microsyringe, and in-situ ring-opening-condensation cascade polymerization was carried out under nitrogen atmosphere to give the corresponding polymer. Samples were taken every 30 minutes during the reaction and the reaction was stopped after 120 minutes.
The time-dependent change of the molecular weight of the copolyester is shown in fig. 4, which demonstrates the successful synthesis of the target product, and the molecular weight can be controlled by controlling the polymerization time. The functional groups are calculated to be present in the copolyester in an amount of about 9% by weight.
EXAMPLE 3 in situ Ring opening-condensation Cascade polymerization of decamethylene glycol and Musk T mixtures to degradable aliphatic copolyesters (PEBDB)
In a 100 ml one-neck flask were added decanediol (3.00 g) and musk T (10.0 g), and 26.0. mu.l of n-butyl titanate was slowly added through a microsyringe. And (3) placing the single-neck flask into a salt bath kettle, heating to 200 ℃, mechanically stirring, reacting for 10 minutes under the nitrogen atmosphere, and then carrying out vacuum polymerization for 30 minutes to finally generate the corresponding polymer.
The volume exclusion chromatogram is shown in fig. 5, and the measured molecular weight is 20.3 kg per mole, demonstrating successful synthesis of the target product. The functional group content in the copolyester was calculated to be about 23% by weight.
EXAMPLE 4 in situ Ring opening-condensation cascade polymerization of 2,2,3,3,4, 4-hexafluoro-1, 5-pentanediol in combination with Musk T to produce a degradable aliphatic copolyester (PEBFB)
A100 ml three-neck flask was charged with 2,2,3,3,4, 4-hexafluoro-1, 5-pentanediol (0.25 g) and musk T (5.00 g), purged with nitrogen to remove oxygen, placed in a salt bath pan and heated to 220 ℃ and mechanically stirred, followed by slowly adding 10.5. mu.l of n-butyl titanate through a microsyringe to conduct an in situ ring-opening condensation cascade polymerization under nitrogen atmosphere to give the corresponding polymer. Samples were taken every 30 minutes during the reaction and the reaction was stopped after 180 minutes.
The graph of the molecular weight of the copolyester as a function of time is shown in fig. 6, which demonstrates the successful synthesis of the desired product. The functional group is calculated to be present in the copolyester at about 5% by weight.
Example 5 in situ Ring opening-condensation Cascade polymerization of polyethylene glycol adipate diol (PEA) and Moschus T to form degradable aliphatic Multi-Block copolyester (PEB-b-PEA-b-PEB)n
A100 ml three-necked flask was charged with polyethylene glycol adipate glycol (molecular weight 3.81 kg/mol, 1.00 g) and musk T (1.00 g), and purged with nitrogen to remove oxygen. The three-neck flask is placed in a salt bath pot and heated to 220 ℃, and mechanically stirred, and then 4.00 microliters of n-butyl titanate is slowly added through a microsyringe, and the in-situ ring-opening-condensation cascade polymerization reaction is carried out under the nitrogen atmosphere, so as to generate the corresponding polymer. Samples were taken every 30 minutes during the reaction and the reaction was stopped after 120 minutes.
The change of the molecular weight of the copolyester with time is shown in figure 7, which proves the successful synthesis of the target product. The functional groups are calculated to be present in the copolyester in an amount of about 50% by weight.
Example 6 in situ Ring opening-condensation cascade polymerization of polyethylene glycol (PEO) and Moschus T to obtain degradable aliphatic multi-block copolyester (PEB-b-PEO-b-PEB)n
Polyethylene glycol (molecular weight 2.00 kg per mole, 1.00 g) and musk T (1.00 g) were added to a 100 ml single-neck flask, and 4.00 μ l of n-butyl titanate was slowly added by means of a microsyringe. And (3) placing the single-neck flask into a salt bath kettle, heating to 220 ℃, mechanically stirring, reacting for 5 minutes under the nitrogen atmosphere, and then carrying out vacuum polymerization for 20 minutes, 30 minutes and 90 minutes to finally generate the corresponding polymer.
Volume exclusion chromatogram see fig. 8, molecular weight 18.4 kg per mole measured for 20 minutes of polymerization, 25.7 kg per mole measured for 30 minutes, and 50.3 kg per mole measured for 90 minutes, demonstrating successful synthesis of the target product. The functional groups are calculated to be present in the copolyester in an amount of about 50% by weight.
Example 7 formation of degradable aliphatic segmented copolyesters (PEB-b-PTMO-b-PEB)n
In a 100 ml single neck flask were added polytetrahydrofuran diol (molecular weight 2.90 kg per mole, 7.50 g) and musk T (2.50 g), and 20.0 μ l of n-butyl titanate was slowly added by means of a microsyringe. And (3) placing the single-neck flask into a salt bath kettle, heating to 220 ℃, mechanically stirring, reacting for 15 minutes under the nitrogen atmosphere, and then carrying out vacuum polymerization for 30 minutes to finally generate the corresponding polymer.
The volume exclusion chromatogram is shown in fig. 9, and the measured molecular weight is 68.7 kg per mole, demonstrating successful synthesis of the target product. The functional group is calculated to be present in the copolyester at about 75% by weight.
Example 8 preparation of a polyethylene glycol-block-polypropylene glycol-block-polyethylene glycol triblock copolymer glycol (PEO-b-PPO-bPEO) and musk T are mixed and subjected to in-situ ring-opening condensation cascade polymerization to generate degradable aliphatic multi-block copolyester (PEB-b-PEO-b-PPO-b-PEO-b-PEB)n
A100 ml three-necked flask was charged with polyethylene glycol-block-polypropylene glycol-block-polyethylene glycol triblock copolymer glycol (molecular weight: 2.00 kg/mol, PEO content: 10%, 5.00 g) and musk T (5.00 g), and nitrogen gas was introduced to remove oxygen. The three-neck flask is placed in a salt bath pot and heated to 220 ℃, and mechanically stirred, and then 20.0 microliter of n-butyl titanate is slowly added through a microsyringe, and the in-situ ring-opening-condensation cascade polymerization reaction is carried out under the nitrogen atmosphere, so as to generate the corresponding polymer. Samples were taken every 30 minutes during the reaction and the reaction was stopped after 150 minutes.
The graph of the molecular weight of the copolyester as a function of time is shown in FIG. 10, demonstrating the successful synthesis of the desired product. The functional groups are calculated to be present in the copolyester in an amount of about 50% by weight.
Example 9 preparation of a triblock copolymer glycol from polyethylene glycol-block-polypropylene glycol-block-polyethylene glycol (PEO-b-PPO-bPEO) and musk T are mixed and subjected to in-situ ring-opening condensation cascade polymerization to generate degradable aliphatic multi-block copolyester (PEB-b-PEO-b-PPO-b-PEO-b-PEB)n
Into a 100 ml single-neck flask were charged polyethylene glycol-block-polypropylene glycol-block-polyethylene glycol triblock copolymer glycol (molecular weight 2.90 kg per mole, PEO content 30%, 15.0 g) and musk T (15.0 g), and 60.0 μ l of n-butyl titanate was slowly added by a microsyringe. And (3) placing the single-neck flask into a salt bath kettle, heating to 220 ℃, mechanically stirring, reacting for 15 minutes under the nitrogen atmosphere, and then vacuumizing and polymerizing for 45 minutes to finally generate the corresponding polymer.
The volume exclusion chromatogram is shown in fig. 11, and the measured molecular weight is 40.6 kg per mole, demonstrating successful synthesis of the target product. The functional groups are calculated to be present in the copolyester in an amount of about 50% by weight.
Example 10 aliphatic multiblock copolyester (PEB-b-PEO-b-PPO-b-PEO-b-PEB)nDegradation testing in phosphate buffered saline at 37 degrees Celsius
The phosphate buffer saline solution has pH of 7.2-7.4, wherein the components comprise 80.0 g/L sodium chloride, 2.00 g/L potassium chloride, 36.3 g/L disodium hydrogen phosphate dodecahydrate and 2.40 g/L potassium dihydrogen phosphate; the phosphate-buffered saline solution was divided into a lipase-free group andcontaining lipase (lipase name: Pseudomonas cepacia lipase, enzyme activity: 30.0X 10)3Unit per gram, optimum pH: 7.0) group.
Aliphatic multi-block copolyester (PEB-b-PEO-b-PPO-b-PEO-b-PEB)nA sample (prepared in example 9, sample starting molecular weight 40.6 kg/mol) was immersed in about 1.00 ml of a phosphate buffered saline solution containing a lipase (concentration: 1.00 mg/ml), and the sample was placed in an environment at 37 ℃ for degradation experiments. A separate set of control experiments was performed in phosphate buffered saline without lipase, and other conditions were unchanged. And when the number of days reaches a preset number, taking out the sample, leaching with distilled water, filtering, airing, and weighing the mass change by using an electronic balance.
Aliphatic multi-block copolyester (PEB-b-PEO-b-PPO-b-PEO-b-PEB)nThe degradation profile of the degraded mass as a function of time is shown in FIG. 12. As can be seen, the aliphatic copolyester (PEB-b-PEO-b-PPO-b-PEO-b-PEB)nIn phosphate buffered saline solution at 37 ℃, the mass is not reduced under the condition of not containing lipase; and its mass becomes smaller and smaller under the action of lipase, and the remaining mass at 8 days of degradation is about 43% (mass after degradation/initial mass × 100%). And the residual mass of the polylactic acid is about 75 percent when the polylactic acid is degraded for 8 days under the same condition. Description of aliphatic copolyesters (PEB-b-PEO-b-PPO-b-PEO-b-PEB)nHas good degradability.
Example 11 aliphatic multiblock copolyester (PEB-b-PEO-b-PPO-b-PEO-b-PEB)nDegradation test at 20 ℃ in phosphate buffered saline, without Lipase and with Lipase
About 10.0 mg of aliphatic multi-block copolyester (PEB-b-PEO-b-PPO-b-PEO-b-PEB)nThe sample (prepared in example 8, sample starting molecular weight 21.3 kg/mol) was immersed to about 1.00 ml of a lipase (concentration: 1.00 mg/ml) containing phosphate bufferAnd (4) in a saline solution, placing the sample in an environment of 20 ℃ for degradation experiment. A separate set of control experiments was performed in phosphate buffered saline without lipase, and other conditions were unchanged. And when the number of days reaches a preset number, taking out the sample, leaching with distilled water, filtering, airing, and testing the molecular weight of the sample by using a gel permeation chromatograph.
Aliphatic multi-block copolyester (PEB-b-PEO-b-PPO-b-PEO-b-PEB)nThe degradation profile of the molecular weight of the remaining part of the sample, which was insoluble in water after degradation, as a function of time is shown in FIG. 13. As can be seen, the aliphatic copolyester (PEB-b-PEO-b-PPO-b-PEO-b-PEB)nIn phosphate buffered saline solution at 20 ℃, the degradation speed is very slow under the condition of not containing lipase, the molecular weight is slightly reduced, the degradation speed is accelerated under the action of the lipase, and the molecular weight is reduced from 21.3 kilograms per mole to 15.1 kilograms per mole within 8 days. Under the same experimental conditions, the sample is placed under the refrigeration condition of 4 ℃ for 30 days, and the molecular weight is kept unchanged within the error range of instrumental measurement, which indicates that the aliphatic copolyester has good stability at the temperature.
Example 12 aliphatic multiblock copolyester (PEB-b-PEO-b-PPO-b-PEO-b-PEB)nDegradation testing at 37 ℃ in phosphate buffered saline, without Lipase and with Lipase
About 10.0 mg of aliphatic multi-block copolyester (PEB-b-PEO-b-PPO-b-PEO-b-PEB)nA sample (prepared in example 8, sample starting molecular weight 21.3 kg/mol) was immersed in about 1.00 ml of a phosphate buffered saline solution containing a lipase (concentration: 1.00 mg/ml), and the sample was placed in an environment at 37 ℃ for degradation experiments. A separate set of control experiments was performed in phosphate buffered saline without lipase, and other conditions were unchanged. And when the number of days reaches a preset number, taking out the sample, leaching with distilled water, filtering, airing, and testing the molecular weight of the sample by using a gel permeation chromatograph.
Aliphatic multi-block copolyester (PEB-b-PEO-b-PPO-b-PEO-b-PEB)nThe degradation profile of the degraded molecular weight as a function of time is shown in FIG. 14. As can be seen, the aliphatic copolyester (PEB-b-PEO-b-PPO-b-PEO-b-PEB)nIn phosphate buffered saline solution at 37 ℃, the molecular weight is slightly reduced under the condition of not containing lipase, and the phosphate buffered saline solution can be rapidly degraded under the action of the lipase. Comparing with fig. 13, it is demonstrated that the degradation speed of the aliphatic multi-block copolyester can be adjusted by changing the temperature, and the degradation is faster after the temperature is increased to 37 ℃.
The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims (7)

1. A preparation method of degradable aliphatic copolyester is characterized in that the degradable aliphatic copolyester is prepared by taking aliphatic macrolide musk T as a monomer and diol as an initiator through in-situ ring-opening-condensation cascade polymerization reaction in the presence of a titanate compound catalyst; the diol is small molecular diol or macromolecular diol; the macrodiol contains a polymer segment.
2. The method for preparing degradable aliphatic copolyester according to claim 1, wherein the molecular weight of the small molecular diol is 30 to 400 g per mole; the polymer chain segment contained in the macroglycol is a polyester chain segment or a polyether chain segment; the titanate compound is n-butyl titanate or isobutyl titanate.
3. The method for preparing the degradable aliphatic copolyester according to claim 1, wherein the chemical structural formula of the degradable aliphatic copolyester is as follows:
Figure DEST_PATH_IMAGE001
wherein R is derived from an initiator diol, x is 10 to 250, and y is 2 to 100.
4. The method for preparing degradable aliphatic copolyester according to claim 1, wherein the in-situ ring-opening-condensation cascade polymerization reaction is performed in a nitrogen atmosphere or under vacuum condition; no purification is required after the reaction is finished.
5. The method for preparing the degradable aliphatic copolyester according to claim 1, wherein the temperature of the in-situ ring-opening-condensation cascade polymerization reaction is 180-260 ℃, and the polymerization reaction time is 10-240 minutes.
6. The method for preparing the degradable aliphatic copolyester according to claim 1, wherein the feeding ratio of the monomer to the initiator is 1-100, and the amount of the catalyst is 0.03-2% of the total feeding amount of the monomer and the initiator.
7. The degradable aliphatic copolyester prepared by the preparation method of the degradable aliphatic copolyester according to claim 1 has the following chemical structural formula:
Figure 293983DEST_PATH_IMAGE001
wherein R is derived from an initiator diol, x is 10 to 250, and y is 2 to 100.
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