CN108530642B - Biodegradable triblock hetero-arm star-shaped amphiphilic polymer material and preparation method thereof - Google Patents
Biodegradable triblock hetero-arm star-shaped amphiphilic polymer material and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a biodegradable triblock hetero-arm star-shaped amphiphilic polymer material and a preparation method thereof, wherein cyclic esters such as polyethylene glycol monomethyl ether, L-lactide, glycolide, epsilon-caprolactone, trimethylene carbonate and delta-valerolactone are used as raw materials, a 'nucleus-first and arm-second' synthesis strategy is adopted, benzyl oxymethyl oxirane is firstly used for modifying the terminal hydroxyl group of the polyethylene glycol monomethyl ether, and then the benzyl oxymethyl oxirane is used as an initiator to sequentially initiate ring-opening polymerization of different monomers, so that the triblock hetero-arm star-shaped polymer material consisting of three different polymer chains is finally obtained, and the biodegradable triblock hetero-arm star-shaped amphiphilic polymer material with higher research value and application value is provided for a nano-drug delivery system.
Description
Technical Field
The invention belongs to the technical field of biomedical materials and biomedical engineering, and relates to a biodegradable multi-hybrid-arm star-shaped amphiphilic polymer material and a preparation method thereof.
Background
In recent ten years, the development of nano-drug delivery systems has provided a possibility to solve the serious toxic and side effects of chemotherapy, and biodegradable polymer materials have become an important nano-drug carrier due to good degradability and biocompatibility. The general polymer drug-loaded material is a nanoparticle with a shell-core structure formed by self-assembling amphiphilic (hydrophilic and lipophilic) polymers, and chemotherapeutic drugs can be loaded in a hydrophobic core of the polymer material. The high-molecular drug-loaded material can not only avoid phagocytosis of a human endothelial reticulum System (RES), but also passively target And gather to tumor tissues by utilizing the high Permeability And retention Effect (EPR) of tumor tissue blood vessels, thereby reducing the dosage And frequency of chemotherapeutic drugs, reducing toxic And side effects And improving the curative effect. The triblock hetero-arm star-shaped amphiphilic polymer material becomes a new hotspot for researching a high-polymer drug-carrying material due to the unique material morphology, lower viscosity, higher density of functional group distribution, smaller hydrodynamic radius, higher stability and higher drug-carrying capacity, but the preparation difficulty of the triblock hetero-arm star-shaped amphiphilic polymer material is larger than that of the traditional linear block amphiphilic polymer material due to the unique chemical structure of the triblock hetero-arm star-shaped amphiphilic polymer material.
Under the condition of the same number of arms, the difficulty of preparing the multi-arm star polymer material containing at least two same polymer arms is less than the difficulty of preparing the star polymer material with each arm completely different, so the multi-arm star polymer material prepared at present is mostly the multi-arm star polymer material containing at least two same polymer arms. The patent application No. CN201310685017.0 discloses a thermosensitive hetero-arm star-shaped polymer emulsifier and a preparation method thereof, wherein a synthesis method of 'arm first and core last' is adopted, and a Reversible Addition-Fragmentation Chain Transfer Polymerization (RAFT) method is adopted, so that a core crosslinking hetero-arm polymer emulsifier with thermosensitive property is prepared from a thermosensitive high-molecular linear arm and a water-soluble high-molecular linear arm through a heterogeneous Polymerization crosslinking agent; although a 10-arm star polymer material was prepared, actually two types of polymer arms (a heat-sensitive polymer linear arm and a water-soluble polymer linear arm) were present, and the number of each type of polymer arm was five. The application number of the patent application No. CN201310085237.X discloses a nuclear cross-linked multi-responsive hybrid arm star polymer and a preparation method thereof, wherein a method of synthesizing a core-first arm and a rear arm is adopted, and a Reversible Addition-Fragmentation Chain Transfer Polymerization (RAFT) method is adopted, a cross-linking agent is used as a core, a temperature-responsive arm and a pH-responsive arm are polymerized under the action of an initiator to obtain a nuclear cross-linked hybrid arm star polymer (the number of arms is 6-10) with temperature responsiveness and pH responsiveness, and actually, two types of polymer arms (a temperature-responsive arm and a pH-responsive arm) exist.
In a few patents for preparing star polymer materials with different arms, the star polymer materials mostly contain a non-biodegradable polymer chain, for example, the patent application No. CN200410017531.8 discloses An (ABC) S type hetero-arm star polymer and a preparation method thereof, and the star polymer is obtained by coupling three different polymer arms and lysine or a derivative thereof with three functional groups one by adopting a synthesis method of 'arm first and nucleus last'; on one hand, the adopted polymer arms have poor biocompatibility, so that the polymer arms have biodegradability, which limits the application of the polymer arms in the field of nano-drug delivery systems, and on the other hand, because the adopted synthesis strategy of 'arm first and nucleus second', the polymer arms need to be modified firstly and then coupled to lysine or derivatives thereof, and the preparation process is relatively complicated.
Disclosure of Invention
The invention aims to overcome the defects in the prior art and provide a biodegradable triblock hetero-arm star-shaped amphiphilic polymer material for a nano-drug delivery system, which consists of three sections of polymer chains with different structural units.
The invention also aims to provide a preparation method of the biodegradable triblock hetero-arm star-shaped amphiphilic polymer material, so as to simplify the preparation process and shorten the production period.
The biodegradable triblock hetero-arm star-shaped amphiphilic polymer material has the following chemical structure:
wherein the A chain is polyethylene glycol monomethyl ether, and the B chain and the C chain are homopolymers or copolymers of different biodegradable polyesters. The chain B and the chain C are grafted to the chain A through ring-opening polymerization reaction initiated by hydroxyl. The biodegradable triblock hetero-arm star-shaped amphiphilic polymer material provided by the invention has a hetero-arm star-shaped structure with three polymer chain structural units which are different, and has lower critical material concentration and higher drug loading after being formed into gel in water; meanwhile, polyethylene glycol monomethyl ether is a hydrophilic chain; the B chain and the C chain are formed by ring-opening polymerization of at least one monomer in cyclic esters such as L-lactide, glycolide, epsilon-caprolactone, trimethylene carbonate, delta-valerolactone and the like, and are hydrophobic chains, so that the amphiphilic property of the high polymer material is endowed, and therefore, the high polymer material is a high polymer drug-loaded material with high stability, high drug-loaded capacity and small particle size.
The invention relates to a preparation method of a biodegradable triblock hetero-arm star-shaped amphiphilic high polymer material, which takes cyclic ester monomers such as L-lactide, glycolide, epsilon-caprolactone, trimethylene carbonate, delta-valerolactone and the like and polyethylene glycol monomethyl ether (mPEG) as raw materials, adopts a strategy of 'nucleus first and arm last', and applies a ring-opening polymerization reaction method to prepare the biodegradable hetero-arm star-shaped high polymer material. Firstly, polyethylene glycol monomethyl ether reacts with benzyloxymethyl ethylene oxide, the benzyloxymethyl ethylene oxide is grafted to the hydroxyl of the polyethylene glycol monomethyl ether in a ring-opening manner, so that the end group modification is carried out on the polyethylene glycol monomethyl ether, and the benzyloxymethyl ethylene oxide grafted to the polyethylene glycol monomethyl ether sequentially initiates a first monomer (or a monomer composition consisting of the first monomer and a second monomer) and a third monomer (or a monomer composition consisting of the third monomer and a fourth monomer) to carry out a ring-opening polymerization reaction, so that a three-block hetero-arm star-shaped amphiphilic high polymer material is obtained; the method comprises the following specific steps:
(1) end group modification of mPEG
Under the protection of nitrogen, mixing an organic solution of polyethylene glycol monomethyl ether with the concentration of 0.05-0.27 g/mL with benzyloxymethyl ethylene oxide to obtain a first mixed solution, then, under the conditions of ice bath and stirring, dropwise adding an organic solution of triethylamine into the obtained first mixed solution, and after dropwise adding, stirring and reacting the obtained reaction system at 25-50 ℃ for 1-3 days; after the reaction is finished, carrying out rotary evaporation on the obtained reaction liquid to a viscous state to obtain a first viscous mixture, dripping the first viscous mixture into a second organic solvent for precipitation, and filtering and vacuum-drying the obtained precipitate to obtain solid powder; the molar ratio of the polyethylene glycol monomethyl ether, the benzyloxymethyl oxirane and the triethylamine in the reaction system is 1 (1-10) to 1-10;
(2) preparation of A-B diblock copolymers
Adding the solid product obtained in the step (1) and a first monomer or a monomer composition consisting of the first monomer and a second monomer into a closed reaction container, dropwise adding a stannous octoate toluene solution with the weight concentration of 0.05-2% into the closed reaction container, then carrying out vacuum drying to remove toluene, and carrying out stirring reaction at 90-200 ℃ for 1-3 days; after the reaction is finished, dissolving the obtained product in a third organic solvent, performing rotary evaporation on the obtained solution to a viscous state to obtain a second viscous mixture, dripping the second viscous mixture into a fourth organic solvent for precipitation, and filtering and vacuum-drying the obtained precipitate to obtain solid powder; the weight ratio of the solid product obtained in the step (1) to the first monomer or the monomer composition consisting of the first monomer and the second monomer is (1-10) - (10-1), and the weight of the stannous octoate toluene solution is 0.01-1% of the weight of the solid product obtained in the step (1) and the first monomer or the monomer composition consisting of the first monomer and the second monomer;
(3) protection of the B-terminal hydroxyl group
Under the conditions of ice bath and stirring, dropwise adding an acetyl chloride organic solution into the organic solution of the solid product obtained in the step (2) with the concentration of 0.08-0.25 g/mL, and stirring and reacting the obtained reaction system at 25-50 ℃ for 1-3 days after dropwise adding; after the reaction is finished, carrying out rotary evaporation on the obtained reaction liquid to a viscous state to obtain a third viscous mixture, dripping the third viscous mixture into a sixth organic solvent for precipitation, and filtering and vacuum-drying the obtained precipitate to obtain solid powder; the molar ratio of the solid product obtained in the step (2) to acetyl chloride in the reaction system is 1 (1-10);
(4) preparation of B-A-OH
Adding the organic solution of the solid product obtained in the step (3) with the concentration of 0.067-0.3 g/mL and the organic dispersion of palladium-carbon with the concentration of 0.002-0.06 g/mL into a reaction kettle, introducing 2-5atm hydrogen into the reaction kettle, stirring for reaction for 1-3 days, filtering out palladium-carbon in the obtained reaction liquid after the reaction is finished, and spin-drying and vacuum-drying the reaction liquid to obtain solid powder; the using amount of the palladium-carbon is 0.5-10% of the weight of the solid product obtained in the step (3);
(5) preparation of B-A-C triblock copolymers
Adding the solid product obtained in the step (4), a third monomer or a monomer composition consisting of the third monomer and a fourth monomer into a closed reaction container, dropwise adding a stannous octoate toluene solution with the weight concentration of 0.05-2% into the closed reaction container, then carrying out vacuum drying to remove toluene, and carrying out stirring reaction at 90-200 ℃ for 1-3 days; after the reaction is finished, dissolving the obtained product in a third organic solvent, performing rotary evaporation on the obtained solution to a viscous state to obtain a fourth viscous mixture, then dropping the fourth viscous mixture into the fourth organic solvent for precipitation, and purifying the obtained precipitate to obtain a biodegradable triblock heteroarm star-shaped amphiphilic high polymer material; the weight ratio of the solid product obtained in the step (4) to a third monomer or a monomer composition consisting of the third monomer and a fourth monomer is (1-10): (10:1), wherein the weight of the stannous octoate toluene solution is 0.01-1% of the weight of the solid product obtained in the step (4) and the third monomer or the monomer composition consisting of the third monomer and the fourth monomer.
The purpose of the step (1) is to modify a polyethylene glycol monomethyl ether terminal group, benzyl oxymethylene oxide is adopted to modify the polyethylene glycol monomethyl ether terminal group, benzyl oxymethylene oxide and polyethylene glycol monomethyl ether are subjected to ring-opening polymerization reaction, so that the benzyl oxymethylene oxide is grafted to hydroxyl at the polyethylene glycol monomethyl ether terminal, the benzyl oxymethylene oxide is used as a nucleus of a triblock polymer chain, and simultaneously the benzyl oxymethylene oxide is used as an initiator to sequentially initiate a first monomer (or a monomer composition consisting of the first monomer and a second monomer) or a third monomer (or a monomer composition consisting of the third monomer and a fourth monomer) to be subjected to polymerization reaction. In the step (1), the preparation process of the organic solution of the polyethylene glycol monomethyl ether comprises the following steps: under the protection of nitrogen, dissolving polyethylene glycol monomethyl ether obtained by vacuum drying in a first organic solvent to obtain an organic solution of polyethylene glycol monomethyl ether; the organic solution of triethylamine is obtained by uniformly mixing triethylamine and a first organic solvent, wherein the volume ratio of the triethylamine to the first organic solvent is 1: (2.4-26.8); the first organic solvent is one of dichloromethane, chloroform, dimethylformamide and tetrahydrofuran; the second organic solvent is diethyl ether or petroleum ether, and in order to ensure that the first viscous mixture is completely precipitated, the volume ratio of the second organic solvent to the first viscous mixture is more than or equal to 10: 1.
In the preparation method of the biodegradable triblock hetero-arm star-shaped amphiphilic polymer material, the step (2) aims to perform ring-opening polymerization reaction on a first monomer (or a monomer composition consisting of the first monomer and a second monomer) under the initiation action of a terminal hydroxyl group of a product obtained after the reaction of benzyloxymethyl ethylene oxide and polyethylene glycol monomethyl ether to obtain an A-B diblock copolymer. In order to avoid the influence of water, after the solid product obtained in the step (1), the first monomer or the monomer composition consisting of the first monomer and the second monomer is added into a closed reaction container, the mixture is dried in vacuum at 50-120 ℃ for 1-5 hours, and then stannous octoate toluene solution is dripped. The third organic solvent is one of dichloromethane, chloroform, dimethylformamide and tetrahydrofuran, and the dosage of the third organic solvent is that the obtained product is completely dissolved; the fourth organic solvent is one of methanol, ether and petroleum ether; in order to completely precipitate the second viscous mixture, the volume ratio of the fourth organic solvent to the second viscous mixture is more than or equal to 10: 1.
In the preparation method of the biodegradable triblock hetero-arm star-shaped amphiphilic polymer material, the step (3) aims to protect the hydroxyl at the end of the B chain in the A-B diblock copolymer obtained in the step (2), so that the hydroxyl obtained by reducing only benzyloxy initiates the third monomer (or the monomer composition consisting of the third monomer and the fourth monomer) to carry out ring-opening polymerization, thereby avoiding the condition that the hydroxyl at the end of the B chain initiates the monomer to carry out polymerization reaction to generate a triblock linear polymer material, and ensuring that the target product, namely the ABC type hetero-arm star-shaped polymer material, is obtained. In the step (3), the preparation process of the organic solution of the solid product obtained in the step (2) is as follows: under the protection of nitrogen, dissolving the solid obtained in the step (2) after vacuum drying in a fifth organic solvent to obtain the compound; the acetyl chloride organic solution in the step (3) is obtained by uniformly mixing acetyl chloride and a fifth organic solvent, wherein the volume ratio of the acetyl chloride to the fifth organic solvent is (1-17.5): 250 of (a); the fifth organic solvent is one of dichloromethane, chloroform, dimethylformamide and tetrahydrofuran; the sixth organic solvent is one of methanol, ether and petroleum ether, and in order to enable the third viscous mixture to be completely precipitated, the volume ratio of the sixth organic solvent to the third viscous mixture is more than or equal to 10: 1.
In the preparation method of the biodegradable triblock hetero-arm star-shaped amphiphilic polymer material, the step (4) is to reduce benzyloxy groups in the A-B diblock copolymer into hydroxyl groups so as to initiate ring-opening polymerization of the third monomer (or a monomer composition consisting of the third monomer and the fourth monomer). The invention adopts a hydrogen reduction method, the organic solution of the solid product obtained in the step (3) is obtained by dissolving the solid product obtained in the step (3) after vacuum drying in a seventh organic solvent, and the organic dispersion liquid of palladium carbon is obtained by dispersing the palladium carbon in the seventh organic solvent; the seventh organic solvent is one of dichloromethane, chloroform, dimethylformamide and tetrahydrofuran.
In the preparation method of the biodegradable triblock hetero-arm star-shaped amphiphilic polymer material, the step (5) aims to initiate ring-opening polymerization of a third monomer or a monomer composition consisting of the third monomer and a fourth monomer by hydroxyl groups reduced by hydrogen in the step (4) to obtain a B-A-C triblock star-shaped copolymer. In order to avoid the influence of water, adding the solid product obtained in the step (4), the third monomer or the monomer composition consisting of the third monomer and the fourth monomer into a closed reaction container, then carrying out vacuum drying for 1-5 h at 50-120 ℃, and then dropwise adding a stannous octoate toluene solution. The third organic solvent is one of dichloromethane, chloroform, dimethylformamide and tetrahydrofuran, and the dosage of the third organic solvent is that the obtained product is completely dissolved; the fourth organic solvent is one of methanol, ether and petroleum ether; in order to completely precipitate the fourth viscous mixture, the volume ratio of the fourth organic solvent to the fourth viscous mixture is more than or equal to 10: 1. In order to increase the purity of the product obtained, the precipitate obtained from the dope needs to be purified, in a specific manner: dissolving the obtained precipitate in tetrahydrofuran, dripping the obtained solution into water under stirring, continuously stirring until impurities are completely separated out, centrifuging to remove the impurities insoluble in water, and freeze-drying the obtained supernatant to obtain a biodegradable triblock heteroarm star-shaped amphiphilic polymer material; the tetrahydrofuran is used in an amount that the obtained precipitate is completely dissolved; the volume ratio of the water to the tetrahydrofuran is more than or equal to 10: 1. The product obtained by purification is a spongy solid, the spongy solid is a freeze-dried micelle of a biodegradable triblock hetero-arm star-shaped amphiphilic high polymer material, the micelle is used as a medicine carrying system and has lower critical material concentration and higher medicine carrying capacity, and the micelle is similar to viruses and lipoprotein in size, so that the phagocytosis of reticuloendothelial systems such as liver, spleen and the like can be effectively avoided, and the micelle exists in blood circulation for a longer time and releases the medicine, so that the half-life period of the medicine in vivo is prolonged to a certain extent.
In the preparation method of the biodegradable triblock hetero-arm star-shaped amphiphilic polymer material, the reaction containers adopted in the steps (2) and (5) are carried out in an oxygen-free closed reaction container, and a polymerization tube or a high-pressure reaction kettle can be selected; if a polymerization tube is adopted, the polymerization tube is sealed after toluene is removed in the step (2) and the step (5), and then the stirring reaction is carried out at the temperature of 90-200 ℃.
The preparation method of the biodegradable triblock hetero-arm star-shaped amphiphilic polymer material comprises the following steps of preparing a first monomer, a second monomer, a third monomer and a fourth monomer, wherein the first monomer, the second monomer, the third monomer and the fourth monomer are one of L-lactide, glycolide, epsilon-caprolactone, trimethylene carbonate and delta-valerolactone, and the first monomer and the third monomer are different monomers.
In the preparation method of the biodegradable triblock hetero-arm star-shaped amphiphilic polymer material, the first organic solvent, the third organic solvent and the fifth organic solvent in each step are the same or different, and the second organic solvent, the fourth organic solvent and the sixth organic solvent are the same or different.
The stirring reaction involved in each step of the preparation method of the biodegradable triblock hetero-arm star-shaped amphiphilic polymer material can be realized by magnetic stirring (placing a magnetic stirrer in a reaction vessel before reaction) in order to fully mix reaction liquid.
In the preparation method of the biodegradable triblock hetero-arm star-shaped amphiphilic polymer material, in the step (1) and the step (3), a catalyst is dripped under the ice bath condition, and the purpose is to reduce the initial reaction rate so as to achieve the purpose of preventing side reactions.
Compared with the prior art, the invention has the following beneficial effects:
1. the invention provides a triblock hetero-arm star-shaped amphiphilic polymer material which is a triblock hetero-arm star-shaped structure consisting of three polymer chains (an A chain, a B chain and a C chain) with different structural units, wherein the A chain is polyethylene glycol monomethyl ether and has hydrophilicity; the B chain and the C chain are homopolymers or copolymers of cyclic esters such as L-lactide, glycolide, epsilon-caprolactone, trimethylene carbonate, delta-lactone and the like, have hydrophobicity, are different from the C chain, and are all biodegradable high polymer materials A, B, C, so that a biodegradable tri-block hetero-arm star-shaped amphiphilic high polymer drug-carrying material with high research value and application value is provided for a nano drug delivery system;
2. according to the preparation method of the biodegradable triblock hetero-arm star-shaped amphiphilic polymer material, a synthesis strategy of 'nucleus first and arm last' is adopted, firstly, benzyloxymethyl ethylene oxide is grafted on terminal hydroxyl groups of polyethylene glycol monomethyl ether in a modified manner, the benzyloxymethyl ethylene oxide is taken as a nucleus, meanwhile, the benzyloxymethyl ethylene oxide is taken as an initiator, different monomers are sequentially initiated to carry out ring-opening polymerization, and finally the triblock hetero-arm star-shaped polymer material consisting of three different polymer chains is obtained; compared with the existing synthesis strategy of 'arm first and nucleus second', the preparation process is simplified, the production period is shortened, and the synthesis cost is reduced;
3. according to the preparation method of the biodegradable triblock hetero-arm star-shaped amphiphilic polymer material, provided by the invention, before the ring-opening polymerization of the monomer is initiated for the second time, the terminal hydroxyl group of the product obtained by the polymerization of the monomer initiated for the first time is protected, so that the condition that the terminal hydroxyl group of the polymer chain of the obtained product initiates the polymerization of the monomer to generate the triblock linear polymer material is avoided, and the structure correctness of the final target product is ensured.
Drawings
FIG. 1 is a synthetic route diagram of biodegradable triblock hetero-arm star amphiphilic polymer material prepared by the present invention.
FIG. 2 is the nuclear magnetic spectrum of the PCL-PEG-PLLA biodegradable triblock hetero-arm star-shaped amphiphilic polymer material obtained in the example.
FIG. 3 is an exclusion gel chromatogram of a biodegradable triblock hetero-arm star amphiphilic polymeric material of PCL-PEG-PLLA obtained in example.
Detailed Description
The technical solutions of the embodiments of the present invention will be described clearly and completely with reference to the accompanying drawings, and it is to be understood that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The synthetic route diagram for preparing the biodegradable triblock hetero-arm star-shaped amphiphilic high polymer material is shown in figure 1, firstly polyethylene glycol monomethyl ether reacts with benzyloxymethyl ethylene oxide, the benzyloxymethyl ethylene oxide is grafted to the hydroxyl of the polyethylene glycol monomethyl ether in a ring-opening manner so as to modify the terminal group of the polyethylene glycol monomethyl ether, and the benzyloxymethyl ethylene oxide grafted to the polyethylene glycol monomethyl ether sequentially initiates a ring-opening polymerization reaction of a first monomer (or a monomer composition consisting of the first monomer and a second monomer) and a third monomer (or a monomer composition consisting of the third monomer and a fourth monomer), so that the triblock hetero-arm star-shaped amphiphilic high polymer material is obtained. The following will clearly and completely describe the preparation process of the biodegradable triblock hetero-arm star-shaped amphiphilic polymer material in combination with examples 1 to 4.
Example 1
The PCL-PEG-PLLA biodegradable triblock hetero-arm star amphiphilic polymer material prepared by the embodiment is prepared by the following steps:
(1) end group modification of mPEG
Introducing nitrogen into a mouth-branched bottle for 5 minutes, then adding 6g of polyethylene glycol monomethyl ether (Mn ═ 2000) subjected to vacuum drying into the mouth-branched bottle under the protection of the nitrogen, adding 30ml of dichloromethane, and stirring until the dichloromethane is dissolved to obtain a dichloromethane solution of the polyethylene glycol monomethyl ether; then adding 2.29mL of benzyloxymethyl ethylene oxide into a dichloromethane solution of polyethylene glycol monomethyl ether, mixing to obtain a first mixed solution, then under the conditions of ice bath and magnetic stirring, dropwise adding a dichloromethane solution of triethylamine (obtained by uniformly mixing 4.17mL of triethylamine and 10mL of dichloromethane) into the obtained first mixed solution, after dropwise adding, moving the bottle with the mouth into an oil bath at 30 ℃, and carrying out magnetic stirring reaction for 3 days; after the reaction is finished, carrying out rotary evaporation on the obtained reaction liquid to a viscous state to obtain a first viscous mixture, dripping 15mL of the first viscous mixture into 200mL of diethyl ether for precipitation, and filtering and vacuum-drying the obtained precipitate to obtain 5.9g of white solid powder;
(2) preparation of PCL-mPEG diblock copolymer
Adding 3g of the solid product obtained in the step (1) and 3g of epsilon-caprolactone into a polymerization tube, carrying out vacuum drying for 1h in an oil bath at 80 ℃, removing the oil bath, dropwise adding 0.6mg of stannous octoate toluene solution with the weight concentration of 0.1 wt% into the polymerization tube, carrying out vacuum drying to remove toluene, sealing the polymerization tube, and carrying out magnetic stirring reaction for 2 days in the oil bath at 120 ℃; after the reaction is finished, dissolving the obtained product in 100mL of dichloromethane, then carrying out rotary evaporation on the obtained solution to a viscous state to obtain a second viscous mixture, dripping 5mL of the second viscous mixture into 150mL of methanol for precipitation, and filtering and vacuum-drying the obtained precipitate to obtain 5.8 white solid powder;
(3) protecting PCL terminal hydroxyl in PCL-mPEG
Introducing nitrogen into a bottle with a branch mouth for 5 minutes, then adding 5g of the solid (with the molecular weight of about 4000) obtained in the step (2) after vacuum drying into the bottle with the branch mouth under the protection of the nitrogen, adding 20mL of chloroform, and stirring until the chloroform is dissolved to obtain a chloroform solution of the solid obtained in the step (2); under the conditions of ice bath and magnetic stirring, dropwise adding a chloroform solution of acetyl chloride (obtained by uniformly mixing 0.1mL of acetyl chloride and 20mL of chloroform) into the chloroform solution of the solid product obtained in the step (2), and after dropwise adding, moving the bottle into an oil bath at 25 ℃ for reaction for 3 days; after the reaction is finished, carrying out rotary evaporation on the obtained reaction liquid to a viscous state to obtain a third viscous mixture, dripping 20mL of the third viscous mixture into 350mL of diethyl ether for precipitation, and filtering and vacuum-drying the obtained precipitate to obtain 4.6g of white solid powder;
(4) preparation of PCL-mPEG-OH
Dissolving 3g of the solid obtained in the step (3) in 10mL of dichloromethane, simultaneously uniformly dispersing 0.3g of palladium carbon in 10mL of dichloromethane, then adding the dichloromethane solution of the solid obtained in the step (3) and the dichloromethane dispersion liquid of the palladium carbon into a reaction kettle, introducing hydrogen into the reaction kettle until the pressure in the kettle is 3atm, then placing the reaction kettle on a magnetic stirrer to stir for 1 day, filtering out the palladium carbon in the obtained reaction liquid after the reaction is finished, and spin-drying and vacuum-drying the reaction liquid to obtain 2.7g of white solid powder;
(5) the preparation is PCL-PEG-PLLA biodegradable triblock hetero-arm star amphiphilic polymer material
Adding 2g of the solid product obtained in the step (4) and 1g L-lactide into a polymerization tube, dropwise adding 0.3mg of stannous octoate toluene solution with weight concentration of 0.1 wt% into the polymerization tube, then carrying out vacuum drying to remove toluene, sealing the polymerization tube, and carrying out magnetic stirring reaction in an oil bath at 120 ℃ for 2 days; after the reaction is finished, dissolving the obtained solid in 100mL of dichloromethane, then carrying out rotary evaporation on the obtained solution until the obtained solution is viscous to obtain a fourth viscous mixture, dripping 8mL of the fourth viscous mixture into 200mL of methanol for precipitation, finally dissolving the obtained precipitate in 30mL of tetrahydrofuran, dripping the obtained solution into 2000mL of water under the stirring state, continuously stirring until impurities are completely separated out, centrifuging to remove the impurities insoluble in water, and carrying out freeze drying on the obtained supernatant to obtain 2.6g of white spongy solid, namely the heteroarm star-shaped high polymer material.
The PCL-PEG-PLLA biodegradable triblock hetero-arm star-shaped amphiphilic polymer material obtained in the example is subjected to nuclear magnetic resonance testing (the testing condition is 400 MHz)1H NMR,CDCl3Solvent), the nuclear magnetic spectrum obtained is shown in fig. 2, and it can be seen from fig. 2 that the proton peaks at 3.35 and 3.7ppm of chemical shift belong to the hydrogen atom of the polyethylene glycol monomethyl ether segment, and the proton peaks of the PCL segment appear at 1.4, 1.7, 2.3 and 4.1 ppm; proton peaks for the PLLA segment occurred at 1.6 and 5.2 ppm. Calculating the molecular weight of the polymer material according to the proton peak integral area5979 is very similar to the molecular weight 6000 of PCL-PEG-PLLA, so it can be seen that the hetero-arm star polymer material obtained in example 1 meets the target product.
The molecular weight distribution of the PCL-PEG-PLLA biodegradable triblock hetero-arm star-shaped amphiphilic polymer material obtained in the embodiment is tested, and the obtained exclusion gel chromatogram is shown in FIG. 3, wherein the PDI (Polymer dispersion index) is 1.21, which shows that the molecular weight distribution is narrow and the influence on the performances such as drug loading capacity, particle size and the like of the polymer material is small.
Example 2
The preparation method of the PCL-PEG-PGA biodegradable triblock hetero-arm star-shaped amphiphilic polymer material comprises the following steps:
(1) end group modification of mPEG
Introducing nitrogen into a branch mouth bottle for 10 minutes, then adding 8g of polyethylene glycol monomethyl ether (Mn ═ 2000) after vacuum drying into the branch mouth bottle under the protection of the nitrogen, adding 30ml of chloroform, and stirring until the chloroform is dissolved to obtain a chloroform solution of the polyethylene glycol monomethyl ether; then adding 0.61mL of benzyloxymethyl ethylene oxide into chloroform solution of polyethylene glycol monomethyl ether, mixing to obtain a first mixed solution, then under the conditions of ice bath and magnetic stirring, dropwise adding a chloroform solution of triethylamine (obtained by uniformly mixing 0.56mL of triethylamine and 15mL of chloroform) into the obtained first mixed solution, after dropwise adding, moving the bottle into an oil bath at 50 ℃, and carrying out magnetic stirring reaction for 1 day; after the reaction is finished, carrying out rotary evaporation on the obtained reaction liquid to a viscous state to obtain a first viscous mixture, then dripping 20mL of the first viscous mixture into 500mL of diethyl ether for precipitation, and filtering and vacuum-drying the obtained precipitate to obtain 7.7g of white solid powder;
(2) preparation of PCL-mPEG diblock copolymer
Adding 4g of the solid product obtained in the step (1) and 40g of epsilon-caprolactone into a polymerization tube, carrying out vacuum drying for 1h in an oil bath at 120 ℃, removing the oil bath, dropwise adding 0.44g of stannous octoate toluene solution with the weight concentration of 0.05 wt% into the polymerization tube, carrying out vacuum drying to remove toluene, sealing the polymerization tube, and carrying out magnetic stirring reaction for 1 day in the oil bath at 200 ℃; after the reaction is finished, dissolving the obtained product in 600mL of dichloromethane, then carrying out rotary evaporation on the obtained solution until the obtained solution is viscous to obtain a second viscous mixture, dripping 50mL of the second viscous mixture into 750mL of diethyl ether for precipitation, and filtering and vacuum-drying the obtained precipitate to obtain 41.8 white solid powder;
(3) protecting PCL terminal hydroxyl in PCL-mPEG
Introducing nitrogen into a branch mouth bottle for 10 minutes, then adding 4.4g of the solid (with the molecular weight of about 22000) obtained in the step (2) after vacuum drying into the branch mouth bottle under the protection of the nitrogen, adding 30mL of DMF, and stirring until the DMF solution of the solid obtained in the step (2) is dissolved; under the conditions of ice bath and magnetic stirring, dripping a DMF solution of acetyl chloride (obtained by uniformly mixing 0.14mL of acetyl chloride and 10mL of DMF) into the DMF solution of the solid product obtained in the step (2), and after the dripping is finished, moving the bottle with the mouth into an oil bath at 40 ℃ for reaction for 3 days; after the reaction is finished, carrying out rotary evaporation on the obtained reaction liquid to a viscous state to obtain a third viscous mixture, dripping 10mL of the third viscous mixture into 150mL of diethyl ether for precipitation, and filtering and vacuum-drying the obtained precipitate to obtain 4.2g of white solid powder;
(4) preparation of PCL-mPEG-OH
Dissolving 4g of the solid obtained in the step (3) in 50mL of dichloromethane, simultaneously uniformly dispersing 0.2g of palladium carbon in 10mL of dichloromethane, then adding the dichloromethane solution of the solid obtained in the step (3) and the dichloromethane dispersion liquid of the palladium carbon into a reaction kettle, introducing hydrogen into the reaction kettle until the air pressure is 2atm, then placing the reaction kettle on a magnetic stirrer for stirring reaction for 3 days, filtering out the palladium carbon in the obtained reaction liquid after the reaction is finished, and spin-drying and vacuum-drying the reaction liquid to obtain 3.9g of white solid powder;
(5) preparation of PCL-PEG-PGA biodegradable triblock hetero-arm star-shaped amphiphilic polymer material
Adding 3g of the solid product obtained in the step (4) and 3g of glycolide into a polymerization tube, dropwise adding 0.06g of stannous octoate toluene solution with the weight concentration of 0.05 wt% into the polymerization tube, then carrying out vacuum drying to remove toluene, sealing the polymerization tube, and carrying out magnetic stirring reaction in an oil bath at 200 ℃ for 1 day; after the reaction is finished, dissolving the obtained solid in 150mL of dichloromethane, then carrying out rotary evaporation on the obtained solution until the obtained solution is viscous to obtain a fourth viscous mixture, dripping 18mL of the fourth viscous mixture into 250mL of diethyl ether for precipitation, finally dissolving the obtained precipitate in 60mL of tetrahydrofuran, dripping the obtained solution into 600mL of water under the stirring state, continuously stirring until impurities are completely separated out, centrifuging to remove the impurities insoluble in water, and carrying out freeze drying on the obtained supernatant to obtain 5.7g of white spongy solid, namely the heteroarm star-shaped high polymer material.
Example 3
The preparation method of the PVL-PEG-PLLA biodegradable triblock hetero-arm star-shaped amphiphilic polymer material comprises the following steps:
(1) end group modification of mPEG
Introducing nitrogen into a mouth-branched bottle for 3 minutes, then adding 5g of polyethylene glycol monomethyl ether (Mn ═ 5000) subjected to vacuum drying into the mouth-branched bottle under the protection of the nitrogen, adding 100ml of tetrahydrofuran, and stirring until the tetrahydrofuran is dissolved to obtain a tetrahydrofuran solution of the polyethylene glycol monomethyl ether; then adding 1.52mL of benzyloxymethyl ethylene oxide into the tetrahydrofuran solution of polyethylene glycol monomethyl ether, mixing to obtain a first mixed solution, then under the conditions of ice bath and magnetic stirring, dropwise adding the tetrahydrofuran solution of triethylamine (uniformly mixed by 1.39mL of triethylamine and 10mL of tetrahydrofuran) into the obtained first mixed solution, after dropwise adding, moving the bottle with the mouth into an oil bath at 25 ℃, and carrying out magnetic stirring reaction for 2 days; after the reaction is finished, carrying out rotary evaporation on the obtained reaction liquid to a viscous state to obtain a first viscous mixture, then dripping 7mL of the first viscous mixture into 200mL of petroleum ether for precipitation, and filtering and vacuum-drying the obtained precipitate to obtain 4.9g of white solid powder;
(2) preparation of PVL-mPEG diblock copolymer
Adding 4g of the solid product obtained in the step (1) and 0.8g of delta-valerolactone into a polymerization tube, carrying out vacuum drying for 5h in an oil bath at 50 ℃, removing the oil bath, dropwise adding 0.48mg of stannous octoate toluene solution with the weight concentration of 2 wt% into the polymerization tube, carrying out vacuum drying to remove toluene, sealing the polymerization tube, and carrying out magnetic stirring reaction for 3 days in the oil bath at 90 ℃; after the reaction is finished, dissolving the obtained product in 200mL tetrahydrofuran, then carrying out rotary evaporation on the obtained solution to a viscous state to obtain a second viscous mixture, dripping 10mL of the second viscous mixture into 200mL methanol for precipitation, and filtering and vacuum-drying the obtained precipitate to obtain 7.9 white solid powder;
(3) protection of PVL terminal hydroxyl groups in PVL-mPEG
Introducing nitrogen into a bottle with a branch mouth for 3 minutes, then adding 3g of the solid (with the molecular weight of about 6000) obtained in the step (2) after vacuum drying into the bottle with the branch mouth under the protection of the nitrogen, adding 30mL of chloroform, and stirring until the chloroform is dissolved to obtain a chloroform solution of the solid obtained in the step (2); under the conditions of ice bath and magnetic stirring, dropwise adding a chloroform solution of acetyl chloride (obtained by uniformly mixing 0.04mL of acetyl chloride and 10mL of chloroform) into the chloroform solution of the solid product obtained in the step (2), and after dropwise adding, moving the bottle into an oil bath at 50 ℃ for reaction for 1 day; after the reaction is finished, carrying out rotary evaporation on the obtained reaction liquid to a viscous state to obtain a third viscous mixture, dripping 10mL of the third viscous mixture into 100mL of methanol for precipitation, and filtering and vacuum-drying the obtained precipitate to obtain 2.8g of white solid powder;
(4) preparation of PVL-mPEG-OH
Dissolving 2g of the solid obtained in the step (3) in 30mL of DMF, simultaneously uniformly dispersing 0.01g of palladium-carbon in 5mL of DMF, then adding the DMF solution of the solid obtained in the step (3) and the DMF dispersion liquid of the palladium-carbon into a reaction kettle, introducing hydrogen into the reaction kettle until the air pressure is 5atm, then placing the reaction kettle on a magnetic stirrer for stirring reaction for 2 days, filtering out the palladium-carbon in the obtained reaction liquid after the reaction is finished, and spin-drying and vacuum-drying the reaction liquid to obtain 1.8g of white solid powder;
(5) the preparation is PVL-PEG-PLLA biodegradable triblock hetero-arm star-shaped amphiphilic polymer material
Adding 1g of the solid product obtained in the step (4) and 0.1g L-lactide into a polymerization tube, dropwise adding 0.11mg of stannous octoate toluene solution with the weight concentration of 2 wt% into the polymerization tube, then carrying out vacuum drying to remove toluene, sealing the polymerization tube, and carrying out magnetic stirring reaction in an oil bath at 90 ℃ for 3 days; after the reaction is finished, dissolving the obtained solid in 100mL of tetrahydrofuran, performing rotary evaporation on the obtained solution until the obtained solution is viscous to obtain a fourth viscous mixture, dripping 8mL of the fourth viscous mixture into 80mL of methanol for precipitation, finally dissolving the obtained precipitate in 20mL of tetrahydrofuran, dripping the obtained solution into 800mL of water under the stirring state, continuously stirring until impurities are completely separated out, centrifuging to remove the impurities insoluble in water, and performing freeze drying on the obtained supernatant to obtain 2.4g of white spongy solid, namely the heteroarm star-shaped high polymer material.
Example 4
The PCL-PEG-PLGA biodegradable triblock hetero-arm star-shaped amphiphilic polymer material prepared by the embodiment comprises the following preparation steps:
(1) end group modification of mPEG
Introducing nitrogen into a mouth-branched bottle for 5 minutes, then adding 6g of polyethylene glycol monomethyl ether (Mn ═ 2000) subjected to vacuum drying into the mouth-branched bottle under the protection of the nitrogen, adding 75ml of chloroform, and stirring until the chloroform is dissolved to obtain a chloroform solution of the polyethylene glycol monomethyl ether; then adding 3.66mL of benzyloxymethyl ethylene oxide into chloroform solution of polyethylene glycol monomethyl ether, mixing to obtain a first mixed solution, then under the conditions of ice bath and magnetic stirring, dropwise adding a chloroform solution of triethylamine (obtained by uniformly mixing 2.08mL of triethylamine and 5mL of chloroform) into the obtained first mixed solution, after dropwise adding, moving the bottle with the mouth into an oil bath at 30 ℃, and carrying out magnetic stirring reaction for 2 days; after the reaction is finished, carrying out rotary evaporation on the obtained reaction liquid to a viscous state to obtain a first viscous mixture, then dripping 16mL of the first viscous mixture into 250mL of diethyl ether for precipitation, and filtering and vacuum-drying the obtained precipitate to obtain 5.9g of white solid powder;
(2) preparation of PCL-mPEG diblock copolymer
Adding 5g of the solid product obtained in the step (1) and 5g of epsilon-caprolactone into a polymerization tube, carrying out vacuum drying for 2h in an oil bath at 90 ℃, removing the oil bath, dropwise adding 0.05g of stannous octoate toluene solution with the weight concentration of 1 wt% into the polymerization tube, carrying out vacuum drying to remove toluene, sealing the polymerization tube, and carrying out magnetic stirring reaction for 2 days in the oil bath at 150 ℃; after the reaction is finished, dissolving the obtained product in 250mL of dichloromethane, then carrying out rotary evaporation on the obtained solution until the obtained solution is viscous to obtain a second viscous mixture, dripping 15mL of the second viscous mixture into 3500mL of diethyl ether for precipitation, and filtering and vacuum-drying the obtained precipitate to obtain 4.8 white solid powder;
(3) protecting PCL terminal hydroxyl in PCL-mPEG
Introducing nitrogen into a bottle with a branch mouth for 3 minutes, then adding 4g of the solid (with the molecular weight of about 4000) obtained in the step (2) after vacuum drying into the bottle with the branch mouth under the protection of the nitrogen, adding 50mL of chloroform, and stirring until the solid is dissolved to obtain a chloroform solution of the solid obtained in the step (2); under the conditions of ice bath and magnetic stirring, dropwise adding a chloroform solution of acetyl chloride (obtained by uniformly mixing 0.7mL of acetyl chloride and 10mL of chloroform) into the chloroform solution of the solid product obtained in the step (2), and after dropwise adding, moving the bottle into an oil bath at 35 ℃ for reaction for 2 days; after the reaction is finished, carrying out rotary evaporation on the obtained reaction liquid to a viscous state to obtain a third viscous mixture, dripping 8mL of the third viscous mixture into 150mL of methanol for precipitation, and filtering and vacuum-drying the obtained precipitate to obtain 3.7g of white solid powder;
(4) preparation of PCL-mPEG-OH
Dissolving 3g of the solid obtained in the step (3) in 40mL of DMF, simultaneously uniformly dispersing 0.3g of palladium-carbon in 5mL of DMF, then adding the DMF solution of the solid obtained in the step (3) and the DMF dispersion liquid of the palladium-carbon into a reaction kettle, introducing hydrogen into the reaction kettle until the pressure is 4atm, then placing the reaction kettle on a magnetic stirrer for stirring reaction for 1 day, filtering the palladium-carbon in the obtained reaction liquid after the reaction is finished, and spin-drying and vacuum-drying the reaction liquid to obtain 2.9g of white solid powder;
(5) preparation of PCL-PEG-PLGA biodegradable triblock hetero-arm star-shaped amphiphilic polymer material
Adding 2.5g of the solid product obtained in the step (4), 1.5g of glycolide and 3.5g L-lactide into a polymerization tube, dropwise adding 0.0375g of a 1 wt% stannous octoate toluene solution into the polymerization tube, then carrying out vacuum drying to remove toluene, sealing the polymerization tube, and carrying out magnetic stirring reaction in an oil bath at 150 ℃ for 2 days; after the reaction is finished, dissolving the obtained solid in 150mL of dichloromethane, then carrying out rotary evaporation on the obtained solution until the obtained solution is viscous to obtain a fourth viscous mixture, dropping 20mL of the fourth viscous mixture into 200mL of diethyl ether for precipitation, finally dissolving the obtained precipitate in 60mL of tetrahydrofuran, dropping the obtained solution into 1800mL of water under the stirring state, continuing stirring until impurities are completely separated out, centrifuging to remove the impurities insoluble in water, and carrying out freeze drying on the obtained supernatant to obtain 7.2g of white spongy solid, namely the heteroarm star-shaped high polymer material.
Claims (8)
1. A preparation method of a biodegradable triblock hetero-arm star-shaped amphiphilic polymer material is characterized by comprising the following steps:
(1) end group modification of mPEG
Under the protection of nitrogen, mixing an organic solution of polyethylene glycol monomethyl ether with the mass concentration of 0.05-0.27 g/mL with benzyloxymethyl ethylene oxide to obtain a first mixed solution, then, under the conditions of ice bath and stirring, dropwise adding an organic solution of triethylamine into the obtained first mixed solution, and after dropwise adding, stirring and reacting the obtained reaction system at 25-50 ℃ for 1-3 days; after the reaction is finished, carrying out rotary evaporation on the obtained reaction liquid to a viscous state to obtain a first viscous mixture, dripping the first viscous mixture into a second organic solvent for precipitation, and filtering and vacuum-drying the obtained precipitate to obtain solid powder; the molar ratio of the polyethylene glycol monomethyl ether, the benzyloxymethyl oxirane and the triethylamine in the reaction system is 1 (1-10) to 1-10;
(2) preparation of A-B diblock copolymers
Adding the solid product obtained in the step (1) and a first monomer or a monomer composition consisting of the first monomer and a second monomer into a closed reaction container, dropwise adding a stannous octoate toluene solution with the weight concentration of 0.05-2% into the closed reaction container, then carrying out vacuum drying to remove toluene, and carrying out stirring reaction at 90-200 ℃ for 1-3 days; after the reaction is finished, dissolving the obtained product in a third organic solvent, performing rotary evaporation on the obtained solution to a viscous state to obtain a second viscous mixture, dripping the second viscous mixture into a fourth organic solvent for precipitation, and filtering and vacuum-drying the obtained precipitate to obtain solid powder; the weight ratio of the solid product obtained in the step (1) to the first monomer or the monomer composition consisting of the first monomer and the second monomer is (1-10) - (10-1), and the weight of the stannous octoate toluene solution is 0.01-1% of the weight of the solid product obtained in the step (1) and the first monomer or the monomer composition consisting of the first monomer and the second monomer;
(3) protection of the B-terminal hydroxyl group
Under the conditions of ice bath and stirring, dropwise adding an acetyl chloride organic solution into the organic solution of the solid product obtained in the step (2) with the concentration of 0.08-0.25 g/mL, and stirring and reacting the obtained reaction system at 25-50 ℃ for 1-3 days after dropwise adding; after the reaction is finished, carrying out rotary evaporation on the obtained reaction liquid to a viscous state to obtain a third viscous mixture, dripping the third viscous mixture into a sixth organic solvent for precipitation, and filtering and vacuum-drying the obtained precipitate to obtain solid powder; the molar ratio of the solid product obtained in the step (2) to acetyl chloride in the reaction system is 1 (1-10);
(4) preparation of B-A-OH
Adding the organic solution of the solid product obtained in the step (3) with the concentration of 0.067-0.3 g/mL and the organic dispersion of palladium-carbon with the concentration of 0.002-0.06 g/mL into a reaction kettle, introducing 2-5atm hydrogen into the reaction kettle, stirring for reaction for 1-3 days, filtering out palladium-carbon in the obtained reaction liquid after the reaction is finished, and spin-drying and vacuum-drying the reaction liquid to obtain solid powder; the using amount of the palladium-carbon is 0.5-10% of the weight of the solid product obtained in the step (3);
(5) preparation of B-A-C triblock copolymers
Adding the solid product obtained in the step (4), a third monomer or a monomer composition consisting of the third monomer and a fourth monomer into a closed reaction container, dropwise adding a stannous octoate toluene solution with the weight concentration of 0.05-2% into the closed reaction container, then carrying out vacuum drying to remove toluene, and carrying out stirring reaction at 90-200 ℃ for 1-3 days; after the reaction is finished, dissolving the obtained product in a third organic solvent, performing rotary evaporation on the obtained solution to a viscous state to obtain a fourth viscous mixture, then dropping the fourth viscous mixture into the fourth organic solvent for precipitation, and purifying the obtained precipitate to obtain a biodegradable triblock heteroarm star-shaped amphiphilic high polymer material; the weight ratio of the solid product obtained in the step (4) to a third monomer or a monomer composition consisting of the third monomer and a fourth monomer is (1-10): (10:1), wherein the weight of the stannous octoate toluene solution is 0.01-1% of the weight of the solid product obtained in the step (4) and the third monomer or the monomer composition consisting of the third monomer and the fourth monomer.
2. The method for preparing biodegradable triblock hetero-arm star-shaped amphiphilic polymer material according to claim 1, wherein in the step (1), the preparation process of the organic solution of polyethylene glycol monomethyl ether comprises the following steps: under the protection of nitrogen, dissolving polyethylene glycol monomethyl ether obtained by vacuum drying in a first organic solvent to obtain an organic solution of polyethylene glycol monomethyl ether; the organic solution of triethylamine is obtained by uniformly mixing triethylamine and a first organic solvent, wherein the volume ratio of the triethylamine to the first organic solvent is 1: (2.4-26.8); the first organic solvent is one of dichloromethane, chloroform, dimethylformamide and tetrahydrofuran; the second organic solvent is diethyl ether or petroleum ether.
3. The preparation method of the biodegradable triblock hetero-arm star-shaped amphiphilic polymer material according to claim 1, wherein in the step (2), the solid product obtained in the step (1), the first monomer or the monomer composition consisting of the first monomer and the second monomer is added into a closed reaction container, vacuum drying is carried out for 1-5 hours at 50-120 ℃, and then stannous octoate toluene solution is added dropwise; in the step (5), after the solid product obtained in the step (4) and the third monomer or the monomer composition consisting of the third monomer and the fourth monomer are added into a closed reaction container, vacuum drying is carried out for 1-5 hours at 50-120 ℃, and then a stannous octoate toluene solution is dropwise added.
4. The method for preparing biodegradable triblock hetero-arm star-shaped amphiphilic polymer material according to claim 3, wherein the third organic solvent in the step (2) and the step (5) is one of dichloromethane, chloroform, dimethylformamide and tetrahydrofuran, and the amount of the third organic solvent is that the obtained product is completely dissolved; the fourth organic solvent is one of methanol, ether and petroleum ether.
5. The method for preparing biodegradable triblock hetero-arm star-shaped amphiphilic polymer material according to claim 1, wherein in the step (3), the organic solution of the solid product obtained in the step (2) is prepared by the following steps: under the protection of nitrogen, dissolving the solid product obtained in the step (2) after vacuum drying in a fifth organic solvent to obtain the product; the acetyl chloride organic solution in the step (3) is obtained by uniformly mixing acetyl chloride and a fifth organic solvent, wherein the volume ratio of the acetyl chloride to the fifth organic solvent is (1-17.5): 250 of (a); the fifth organic solvent is one of dichloromethane, chloroform, dimethylformamide and tetrahydrofuran; the sixth organic solvent is one of methanol, diethyl ether and petroleum ether.
6. The method for preparing biodegradable triblock hetero-arm star-shaped amphiphilic polymer material according to claim 1, wherein in the step (4), the organic solution of the solid product obtained in the step (3) is obtained by dissolving the solid product obtained in the step (3) after vacuum drying in a seventh organic solvent, and the organic dispersion liquid of palladium-carbon is obtained by dispersing the palladium-carbon in the seventh organic solvent; the seventh organic solvent is one of dichloromethane, chloroform, dimethylformamide and tetrahydrofuran.
7. The method for preparing biodegradable triblock hetero-arm star-shaped amphiphilic polymer material according to claim 1, wherein in the step (5), the obtained precipitate is purified in a specific manner as follows: dissolving the obtained precipitate in tetrahydrofuran, dripping the obtained solution into deionized water under stirring, continuously stirring until impurities are completely separated out, centrifuging to remove the impurities insoluble in water, and freeze-drying the obtained supernatant to obtain a biodegradable triblock heteroarm star-shaped amphiphilic polymer material; the tetrahydrofuran is used in such an amount that the resulting precipitate is completely dissolved.
8. The method of claim 1, wherein the first, second, third and fourth monomers are one of L-lactide, glycolide, epsilon-caprolactone, trimethylene carbonate and delta-valerolactone, and the first and third monomers are different monomers.
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