CN115449062B - Polyethylene glycol-polyester block copolymer containing sulfobetaine end group and preparation method thereof - Google Patents

Polyethylene glycol-polyester block copolymer containing sulfobetaine end group and preparation method thereof Download PDF

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CN115449062B
CN115449062B CN202211205306.1A CN202211205306A CN115449062B CN 115449062 B CN115449062 B CN 115449062B CN 202211205306 A CN202211205306 A CN 202211205306A CN 115449062 B CN115449062 B CN 115449062B
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block copolymer
polyester block
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sulfobetaine
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孙宇澄
王凯
刘宝良
于目顺
赵英杰
鲁在君
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Shandong Baositai Medical Materials Co ltd
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Abstract

The invention discloses a polyethylene glycol-polyester block copolymer containing a sulfobetaine end group and a preparation method thereof. Firstly, preparing an anionic polymerization initiator by taking N, N-dialkyl ethanolamine containing hydroxyl end groups and a metal organic compound as raw materials; then ethylene oxide and epoxy ester monomers are used as raw materials, an anionic sequential charging method is used for preparing a polyethylene glycol-polyester block copolymer containing N, N-dialkylamino end groups, and then the polyethylene glycol-polyester block copolymer containing the sulfobetaine end groups is prepared by carrying out ring opening reaction on the N, N-dialkylamino end groups and sultone; experimental results prove that the polyethylene glycol-polyester block copolymer containing the sulfobetaine end group is successfully synthesized, and the yield is up to 95%. The polyethylene glycol-polyester block polymer containing the sulfobetaine end group has stronger water absorption, water molecules repel the approach of immunoglobulin, immune reaction is avoided, and great development potential is expected in the field of biomedical materials.

Description

Polyethylene glycol-polyester block copolymer containing sulfobetaine end group and preparation method thereof
Technical Field
The invention belongs to the technical field of high polymer materials, and particularly relates to a polyethylene glycol-polyester block copolymer containing a sulfobetaine end group and a preparation method thereof.
Background
Zwitterionic groups are groups that have both positively and negatively charged regions. Zwitterionic groups have the strongest hydration known to date (each zwitterionic group can adsorb at least 7 to 8 water molecules, whereas each repeat unit of polyethylene glycol can only attract 1 water molecule by hydrogen bonding). When in vivo, the unique hydrophilicity can form a firm hydration layer on the surface of the zwitterionic groups, and the water molecule layer has a repulsive effect on proteins, so that the adsorption of immunoglobulin is blocked, and immune response is not caused. Therefore, the zwitterionic group has potential and wide application prospect in the fields of biological pharmacy and the like.
There are three common zwitterionic groups: the sulfonic acid betaines (SB), carboxylic acid betaines (CB) and Phosphorylcholine (PC) are found to have the most excellent hydrophilic properties.
Polyethylene glycol (PEG) is the first synthetic polymer to be approved by the FDA for use in biological medicine with the lowest level of cellular absorption and excellent biocompatibility. The polyester material is also a synthetic polymer material authenticated by FDA and has biodegradability. The polyethylene glycol-polyester block polymer integrates the advantages of polyethylene glycol and polyester, and is the block copolymer with the application potential in organisms.
The block copolymer containing the zwitterion is a high polymer which combines the zwitterion and the block copolymer together at the molecular level, and the high hydrophilicity and the nonspecific immunity of the zwitterion are introduced on the basis of the performance of the block polymer. Currently, there are reports on zwitterionic containing block copolymer materials. Peng et al (Peng Bin, shen Chong, meng Qin, et al; swelling factor of DA-P123 hydrogels and their use for removal of heavy metal ions from solution [ J ]. University chemical engineering report, 2017,31 (6): 7.) reported a block copolymer PS-b-SBMA having zwitterionic groups in the side groups, by synthesis of a polystyrene macroinitiator (PS-Br) having bromo-end groups, followed by polymerization with methacrylate monomers (SBMA) having betaine zwitterionic side groups to form a block copolymer PS-b-SBMA having betaine zwitterionic side groups; zhang et al (Zhang Q, tang X, wang T, et al thermo-sensitive zwitterionic block copolymers via ATRP [ J ]. RSC Advances,2014,4 (46): 24240.) reported that esterification of an alpha-bromoisobutyryl bromide monomer with a monomethoxy polyethylene glycol produced a polyethylene glycol macroinitiator (MPEG-Br) containing a bromine end group, followed by atom transfer radical polymerization with a methacrylate monomer (SBMA) containing a sulfobetaine zwitterionic pendant group to produce a block copolymer MPEG-b-PSMB containing a zwitterionic group pendant group; zhang et al (W Du, Q Lu, M Zhang, et al, synthesis and Characterization of Folate-Modified Cell Membrane Mimetic Copolymer Micelles for Effective Tumor Cell Internalization [ J ]. ACS Applied Bio Materials,2021,4 (4)) reported that poly (dimethylaminoethyl methacrylate) was used as the monomer and mercaptoethanol was used as the chain transfer agent, and free radical polymerization was employed to prepare a poly (dimethylaminoethyl methacrylate) having a hydroxyl group at the end, which was then reacted with caprolactone under stannous octoate catalysis to synthesize a dimethylaminoethyl methacrylate-polycaprolactone block copolymer, which was further ring-opened with 1,3 propane sultone to synthesize a poly (dimethylaminoethyl methacrylate-polycaprolactone block copolymer having a sulfobetaine side group.
In conclusion, the reported sulfobetaine groups are all positioned on the side groups of the block copolymer, and the literature report of the block copolymer with the sulfobetaine groups positioned at the molecular chain ends is not yet seen.
Disclosure of Invention
Aiming at the problems in the prior art, the invention provides a polyethylene glycol-polyester segmented copolymer containing a sulfobetaine end group and a preparation method thereof.
The first aspect of the invention provides a polyethyleneglycol-polyester block copolymer containing sulfobetaine end groups, which has a general structure shown in the following formula (1):
Figure BDA0003871595230000021
wherein x is an integer of 10 to 5000 and y is an integer of 10 to 5000; r is R 1 is-CH 3 、-CH 2 CH 3 or-CH (CH) 3 ) 2 ；R 2 A linear alkylene group having 3 to 8 carbon atoms; r is R 3 is-CH 2 -、-CH(CH 3 ) -or- (CH) 2 ) 5 -。
The second aspect of the invention provides a preparation method of the polyethylene glycol-polyester block copolymer containing the sulfobetaine end group, which comprises the following steps:
s1, performing electrophilic substitution reaction on N, N-dialkylethanolamine containing hydroxyl end groups and a metal organic compound to obtain an anionic polymerization initiator;
s2, carrying out anionic polymerization reaction on the obtained anionic polymerization initiator, ethylene oxide and epoxy ester monomers to obtain a polyethylene glycol-polyester block copolymer with N, N-dialkylamino end groups;
s3, carrying out ring-opening reaction on the obtained polyethylene glycol-polyester block copolymer with the N, N-dialkyl amino end group and sultone to obtain the polyethylene glycol-polyester block copolymer with the sultaine end group.
Preferably, in step S2, the raw material feeding sequence of the anionic polymerization reaction is as follows: sequentially adding ethylene oxide and epoxy ester monomers into the obtained anionic polymerization initiator.
Preferably, in step S3, the conditions of the ring-opening reaction are as follows: the reaction temperature is between-10 and 100 ℃ and the reaction time is between 2 and 24 hours.
Preferably, the metal organic compound is any one of potassium hydroxide, naphthalene potassium, benzhydryl potassium, tert-butyl potassium alkoxide, sodium hydroxide, naphthalene sodium, benzhydryl sodium, and tert-butyl sodium alkoxide.
Preferably, the epoxy ester monomer is one or more than two of glycolide, lactide and caprolactone.
Preferably, the sultone is any one of propane sultone, butane sultone, pentane sultone, hexane sultone, heptane sultone and octane sultone.
Preferably, in step S3, the process of the ring-opening reaction is terminated with a terminating agent, and the terminating agent is any one of alcohols, acids, amines and water.
The invention has the following beneficial effects:
(1) In the invention, firstly, N-dialkyl ethanolamine containing hydroxyl end groups and metal organic compounds are taken as raw materials, and an anionic polymerization initiator is synthesized through electrophilic substitution reaction; then using ethylene oxide and epoxy ester monomers as raw materials, synthesizing a polyethylene glycol-polyester block copolymer containing N, N-dialkylamino end groups by a (active) anion sequential charging method, and then carrying out ring-opening reaction on the N, N-dialkylamino end groups and sultone to synthesize the polyethylene glycol-polyester block copolymer containing the sultaine end groups; wherein, the sultaine zwitterionic end group is synthesized by adopting the efficient ring-opening reaction of sultone, and the end group functionalization yield is high (up to 95%). The invention has the advantages of rich raw material sources, simple synthesis steps, high batch stability and easy realization of industrialized stable production.
(2) Compared with the traditional polyethylene glycol-polyester block copolymer containing methoxy end groups, the polyethylene glycol-polyester block copolymer containing the sulfobetaine end groups has stronger water absorption capacity due to the introduction of the sulfobetaine end groups (the water absorption capacity is strongest in the zwitterionic groups), is more beneficial to forming a hydration layer in organisms, and water molecules repel the approach of immunoglobulin so as to avoid causing immune reaction, and is expected to have potential and huge development prospect in the field of biomedical materials.
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In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings that are needed in the embodiments will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a GPC chart of N-PEG-b-PLA1 in example 1;
FIG. 2 is an infrared spectrum of S-PEG-b-PLA1 of example 1;
FIG. 3 is a nuclear magnetic resonance hydrogen spectrum of S-PEG-b-PLA1 of example 1.
Detailed Description
In the following description, for purposes of explanation and not limitation, specific details are set forth such as the particular system architecture, techniques, etc., in order to provide a thorough understanding of the embodiments of the present invention. It will be apparent, however, to one skilled in the art that the present invention may be practiced in other embodiments that depart from these specific details.
The present invention provides a polyethylene glycol-polyester block copolymer containing a sulfobetaine end group and a preparation method thereof, which are described in detail below with reference to examples, all of which are necessarily performed under anhydrous and anaerobic conditions, but which are not to be construed as limiting the scope of the present invention.
Example 1
Preparation of a block copolymer (S-PEG-b-PLA 1) containing a sulfobetaine end group, and the specific reaction scheme is shown as follows:
Figure BDA0003871595230000041
the method comprises the following specific steps: adopting two double-connection single-port bottles connected by two 250ml single-port bottles to form an A bottle and a B bottle respectively, baking at 120 ℃ for 3 hours, while the bottle is hot, connecting the A, B bottle to a vacuum tube, introducing argon gas, vacuumizing, baking by an alcohol lamp while cooling the bottle, introducing argon gas, repeating for three times, adding 6.525g of lactide into the B bottle under the argon gas atmosphere, adding stirring magnetons into the A, B bottle, adding 15ml of Tetrahydrofuran (THF) into the A bottle under the ice water bath condition, adding 2.34ml of initiator (N, N-dimethyl ethanolamine potassium), 5ml of ethylene oxide, stirring the A bottle for 24 hours in the ice water bath, stirring for 12 hours at room temperature to form brownish red viscous liquid, and extracting reaction liquid (PEG) to measure M n The mixture is quickly poured into a B bottle and stirred at room temperature for 1.5 to 2 hours to obtain N, N-dialkylamino-terminated polyethylene glycol-polylactide (N-PEG-B-PLA 1), 1.2g of propane sultone is then added, the mixture is stirred at room temperature for 6 hours, 1ml of methanol is added and stirred for 30 minutes, the reaction is terminated, 1ml of 1M HCl and 2ml of ultrapure water are added and stirred for 2 hours, the mixture is poured into an absolute ethanol solution, a white viscous solid is obtained by suction filtration, and the white powdery solid is obtained by drying in a vacuum drying oven for 24 hours, wherein the yield is 95.9 percent. GPC: M n =2000, pdi=1.2. The specific structure characterization results are shown in figures 1-3.
As is clear from the results of FIG. 1, the GPC curve of the N-PEG-b-PLA block copolymer was significantly shifted to the high molecular weight side as compared with the PEG block curve, and the flow-out curve was unimodal, indicating that the N-PEG-b-PLA block copolymer was obtained.
As can be seen from the results of FIG. 2, 3577cm -1 The peak at which is the hydroxyl (-OH) peak, 1723cm -1 The peak at which is carbonyl (-C=O-) peak, 1181cm -1 、956m -1 、723cm -1 The peaks appear at the sulfonic acid groups (-SO) 3 (-) and antisymmetric stretching vibration peaks, thereby demonstrating that this example successfully synthesized S-PEG-b-PLA1.
From the results of fig. 3, it can be seen that the chemical shift δ=3.61 ppm is PEG segment-CH 2 CH 2 Proton peak of O-methylene, proton peak of polylactic acid segment-CH-methylene at chemical shift δ=5.32 ppm, chemistryThe displacement delta=1.20 ppm is polylactic acid chain segment-CH 3 Proton peak of methyl group, its area percentage is equal to about 6:1:3, basically consistent with the feeding amount; formants at 4.2ppm and 3.25ppm are respectively assigned to S-CH 2 (h)、CH 3 -N-CH 3 The integral area ratio of the protons in (1): 3.04, to theory ratio 1:3, and thus, the successful synthesis of S-PEG-b-PLA1 by this example. The end group content is calculated by nuclear magnetism H spectrum contrast of integral ratio of methylene g, H and f on sulfonic group and two methyl groups i and j connected with N according to the following formula:
the sulfobetaine end group content = [ sum of integrated areas of g, h, f/sum of integrated areas of i, j ] ×100% was finally calculated to give a yield of 95% of sulfobetaine end groups.
Example 2
The preparation method of the block copolymer (S-PEG-b-PLA 2) containing the sulfobetaine end group comprises the following steps:
adopting two double-connection single-mouth bottles connected by two 250ml single-mouth bottles to form an A bottle and a B bottle respectively, baking at 120 ℃ for 3 hours, while the bottle is hot, connecting the A, B bottle to a vacuum tube, introducing argon gas, vacuumizing, baking by an alcohol lamp while cooling the bottle, introducing argon gas, repeating for three times, adding 6.525g of lactide into the B bottle under the argon gas atmosphere, adding stirring magnetons into the A, B bottle, adding 15ml of Tetrahydrofuran (THF) into the A bottle under the ice water bath condition, adding 1.42ml of initiator (N, N-diethyl ethanolamine potassium), 5ml of ethylene oxide, stirring the A bottle for 24 hours in the ice water bath, stirring for 12 hours at room temperature to form brownish red viscous liquid, and extracting the reaction liquid (PEG) to measure M n =2500, quickly pouring into a B bottle, stirring at room temperature for 1.5-2 h, then adding 1.2g of butanesultone, stirring at room temperature for 6h, adding 1ml of methanol, stirring for 30 min, stopping the reaction, adding 1ml of 1m HCl, 2ml of ultrapure water, stirring for 2h, pouring into an absolute ethanol solution, suction-filtering to obtain a white viscous solid, and drying in a vacuum drying oven for 24h to obtain a white powdery solid with the yield of 94.2%. GPC: m is M n ＝5000，PDI＝1.2。
Example 3
The preparation steps of the block copolymer (S-PEG-b-PLA 3) containing the sulfobetaine end group are as follows:
adopts self-controlTwo 250ml single-mouth bottles are connected to form a bottle A and a bottle B respectively, baking is carried out at 120 ℃ for 3 hours, while the bottle A, B is connected to a vacuum tube, argon is introduced into the vacuum tube, after the bottle is cooled, vacuumizing is carried out, baking is carried out by an alcohol lamp while vacuumizing, after cooling, argon is introduced into the bottle B, repeating for three times, under argon atmosphere, 6.525g of lactide is added into the bottle B, stirring magnetic seeds are respectively added into the bottle A, B, 15ml of Tetrahydrofuran (THF) is added into the bottle A under ice water bath condition, 5.71ml of initiator (N, N-dimethyl ethanolamine potassium) is added into the bottle A, 2ml of ethylene oxide is stirred for 24 hours in ice water bath, stirring is carried out for 12 hours at room temperature, a brownish red viscous liquid is formed, and M is measured by extracting reaction liquid (PEG) n =500, quickly pouring into a B bottle, stirring at room temperature for 1.5-2 h, then adding 0.75g of heptanesultone, stirring at room temperature for 6h, adding 1ml of methanol, stirring for 30 min, stopping the reaction, adding 1ml of 1m HCl, 2ml of ultrapure water, stirring for 2h, pouring into an absolute ethanol solution, suction-filtering to obtain a white viscous solid, and drying in a vacuum drying oven for 24h to obtain a white powdery solid with a yield of 93.6%. GPC: m is M n ＝1000，PDI＝1.2。
Example 4
The preparation method of the block copolymer (S-PEG-b-PLA 4) containing the sulfobetaine end group comprises the following steps:
adopting two double-connection single-mouth bottles connected by two 250ml single-mouth bottles to form an A bottle and a B bottle respectively, baking at 120 ℃ for 3 hours, while the bottle is hot, connecting the A, B bottle to a vacuum tube, introducing argon gas, vacuumizing, baking by an alcohol lamp while cooling the bottle, introducing argon gas, repeating for three times, adding 6.525g of lactide into the B bottle under the argon gas atmosphere, adding stirring magnetons into the A, B bottle, adding 15ml of Tetrahydrofuran (THF) into the A bottle under the ice water bath condition, adding 0.12ml of initiator (N, N-dimethyl ethanolamine potassium), 20ml of ethylene oxide, stirring the A bottle for 24 hours in the ice water bath, stirring the A bottle for 12 hours at room temperature to form brownish red viscous liquid, and extracting the reaction liquid (PEG) to measure M n =110000, rapidly pouring into a B bottle, stirring at room temperature for 1.5-2 h, then adding propane sultone 1.45g, stirring at room temperature for 6h, adding 1ml methanol, stirring for 30 min, stopping the reaction, adding 1m HCl 1ml,2ml ultra-pure water, stirring for 2h, pouring into an absolute ethanol solution, suction-filtering to obtain a white viscous solid, and drying in a vacuum drying oven for 24h to obtain a white powdery solid with a yield of 94.2%. GPC:M n ＝220000，PDI＝1.2。
example 5
The preparation method of the block copolymer (S-PEG-b-PCL 1) containing the sulfobetaine end group comprises the following steps:
adopting two double-connection single-port bottles connected by two 250ml single-port bottles to form an A bottle and a B bottle respectively, baking at 120 ℃ for 3 hours, connecting the A, B bottles to a vacuum tube while being hot, introducing argon gas, vacuumizing while baking by an alcohol lamp after the bottles are cooled, introducing argon gas after cooling, repeating for three times, adding 5.135g caprolactone into the B bottle under the argon gas atmosphere, adding 15ml Tetrahydrofuran (THF) into the A bottle under the condition of ice water bath, adding 0.87ml of initiator (N, N-dimethyl ethanolamine potassium), 5ml of ethylene oxide, stirring the A bottle for 24 hours in the ice water bath, stirring the A bottle for 12 hours at room temperature to form brownish red viscous liquid, and extracting the reaction liquid (PEG) to measure M n =4000, rapidly pouring into a B bottle, stirring at room temperature for 1.5-2 h, then adding propane sultone 1.2g, stirring at room temperature for 6h, adding 1ml methanol, stirring for 30 min, stopping the reaction, adding 1m HCl 1ml,2ml ultra-pure water, stirring for 2h, pouring into an absolute ethanol solution, suction-filtering to obtain a white viscous solid, and drying in a vacuum drying oven for 24h to obtain a white powdery solid with a yield of 93.4%. GPC: m is M n ＝8000，PDI＝1.2。
Example 6
The preparation method of the block copolymer (S-PEG-b-PCL 2) containing the sulfobetaine end group comprises the following steps:
adopting two double-connection single-port bottles connected by two 250ml single-port bottles to form an A bottle and a B bottle respectively, baking at 120 ℃ for 3 hours, while the bottle is hot, connecting the A, B bottle to a vacuum tube, introducing argon, vacuumizing, baking by an alcohol lamp while cooling, introducing argon, repeating for three times, adding 5.135g caprolactone into the B bottle under the argon atmosphere, adding stirring magnetrons into the A, B bottle, adding 15ml Tetrahydrofuran (THF) into the A bottle under the ice water bath condition, adding 0.87ml of initiator (N, N-diethyl ethanolamine potassium), 5ml of ethylene oxide, stirring the A bottle for 24 hours in the ice water bath, stirring the A bottle for 12 hours at room temperature to form brownish red viscous liquid, and extracting the reaction liquid (PEG) to measure M n =4000, rapidly pouring into a B bottle, stirring at room temperature for 1.5-2 h, then adding 1.2g of pentasultone, stirring at room temperature for 6h, adding1ml of methanol was added and stirred for 30 minutes, the reaction was terminated, 1ml of 1M HCl, 2ml of ultrapure water was added and stirred for 2 hours, and the mixture was poured into an absolute ethanol solution, and a white viscous solid was obtained by suction filtration and dried in a vacuum drying oven for 24 hours, to obtain a white powdery solid with a yield of 95.3%. GPC: m is M n ＝8000，PDI＝1.2。
Example 7
The preparation method of the block copolymer (S-PEG-b-PCL 3) containing the sulfobetaine end group comprises the following steps:
adopting two double-connection single-port bottles connected by two 250ml single-port bottles to form an A bottle and a B bottle respectively, baking at 120 ℃ for 3 hours, while the bottle is hot, connecting the A, B bottle to a vacuum tube, introducing argon gas, vacuumizing, baking by an alcohol lamp while cooling the bottle, introducing argon gas, repeating for three times, adding 5.135g of caprolactone into the B bottle under the argon gas atmosphere, adding stirring magnetrons into the A, B bottle respectively, adding 15ml of Tetrahydrofuran (THF) into the A bottle under the ice water bath condition, adding 0.7ml of initiator (N, N-dimethyl ethanolamine potassium), 5ml of ethylene oxide, stirring the A bottle for 24 hours in the ice water bath, stirring the A bottle at room temperature for 12 hours to form brownish red viscous liquid, and extracting the reaction liquid (PEG) to measure M n =5000, rapidly pouring into a B bottle, stirring at room temperature for 1.5-2 h, then adding 0.75g of butanesultone, stirring at room temperature for 6h, adding 1ml of methanol, stirring for 30 min, stopping the reaction, adding 1ml of 1m HCl, 2ml of ultrapure water, stirring for 2h, pouring into an absolute ethanol solution, suction-filtering to obtain a white viscous solid, and drying in a vacuum drying oven for 24h to obtain a white powdery solid with a yield of 94.4%. GPC: m is M n ＝10000，PDI＝1.2。
Example 8
The preparation method of the block copolymer (S-PEG-b-PCL 4) containing the sulfobetaine end group comprises the following steps:
adopting two double-connection single-mouth bottles connected by two self-made 250ml single-mouth bottles to form an A bottle and a B bottle respectively, baking at 120 ℃ for 3 hours, while the bottle is hot, connecting the A, B bottle to a vacuum tube, introducing argon gas, vacuumizing, baking by an alcohol lamp while vacuumizing, cooling, introducing argon gas, repeating for three times, adding 5.135g caprolactone into the B bottle under the argon gas atmosphere, adding 15ml Tetrahydrofuran (THF), 7ml of initiator (N, N-dimethyl ethanolamine potassium) and 5ml epoxy into the A bottle under the ice water bath condition, wherein 5.135g caprolactone is added into the B bottle under the A, B bottle under the argon gas atmosphereEthane, A bottle ice water bath stirring 24h, room temperature stirring 12h, forming brownish red viscous liquid, extracting reaction liquid (PEG) to obtain M n =500, quickly pouring into a B bottle, stirring at room temperature for 1.5-2 h, then adding 1.45g of octasultone, stirring at room temperature for 6h, adding 1ml of methanol, stirring for 30 min, stopping the reaction, adding 1ml of 1m HCl, 2ml of ultrapure water, stirring for 2h, pouring into an absolute ethanol solution, suction-filtering to obtain a white viscous solid, and drying in a vacuum drying oven for 24h to obtain a white powdery solid with the yield of 93.1%. GPC: m is M n ＝1000，PDI＝1.2。
Example 9
The preparation method of the block copolymer (S-PEG-b-PGA 1) containing the sulfobetaine end group comprises the following steps:
adopting two double-connection single-port bottles connected by two 250ml single-port bottles to form an A bottle and a B bottle respectively, baking at 120 ℃ for 3 hours, while the bottle is hot, connecting the A, B bottle to a vacuum tube, introducing argon, vacuumizing, baking by an alcohol lamp while cooling, introducing argon, repeating for three times, adding 2.32g glycolide into the B bottle under the argon atmosphere, adding stirring magnetons into the A, B bottles respectively, adding 15ml Tetrahydrofuran (THF) into the A bottle under the ice water bath condition, adding 1.4ml of initiator (N, N-dimethylethanolamine potassium) and 5ml of ethylene oxide into the A bottle, stirring for 24 hours in the ice water bath, stirring for 12 hours at room temperature to form brownish red viscous liquid, and extracting reaction liquid (PEG) to measure M n =2500, quickly pouring into a B bottle, stirring at room temperature for 1.5-2 h, then adding 1.45g of octasultone, stirring at room temperature for 6h, adding 1ml of methanol, stirring for 30 min, stopping the reaction, adding 1ml of 1m HCl, 2ml of ultrapure water, stirring for 2h, pouring into an absolute ethanol solution, suction-filtering to obtain a white viscous solid, and drying in a vacuum drying oven for 24h to obtain a white powdery solid with the yield of 95.1%. GPC: m is M n ＝5000，PDI＝1.2。
Example 10
The preparation method of the block copolymer (S-PEG-b-PGA 2) containing the sulfobetaine end group comprises the following steps:
adopting two double-connection single-mouth bottles connected by two self-made 250ml single-mouth bottles to form an A bottle and a B bottle respectively, baking at 120 ℃ for 3 hours, connecting a A, B bottle to a vacuum tube while the bottle is hot, introducing argon, vacuumizing after the bottle is cooled, and baking by an alcohol lamp while vacuumizingAfter cooling, argon is introduced, the process is repeated three times, under the argon atmosphere, 2.32g glycolide is added into a B bottle, stirring magnetons are respectively added into a A, B bottle, 15ml Tetrahydrofuran (THF) is added into an A bottle under the ice water bath condition, 3.5ml of initiator (N, N-dimethylethanolamine potassium) and 5ml of ethylene oxide are added into the A bottle, the A bottle is stirred for 24 hours in the ice water bath, the room temperature is stirred for 12 hours, a brownish red viscous liquid is formed, and M is measured by extracting reaction liquid (PEG) n =1500, rapidly pouring into a B bottle, stirring at room temperature for 1.5-2 h, then adding 0.75g of butanesultone, stirring at room temperature for 6h, adding 1ml of methanol, stirring for 30 min, stopping the reaction, adding 1ml of 1m HCl, 2ml of ultrapure water, stirring for 2h, pouring into an absolute ethanol solution, suction-filtering to obtain a white viscous solid, and drying in a vacuum drying oven for 24h to obtain a white powdery solid with a yield of 94.6%. GPC: m is M n ＝3000，PDI＝1.2。
Example 11
The preparation method of the block copolymer (S-PEG-b-PGA 3) containing the sulfobetaine end group comprises the following steps:
adopting two double-connection single-port bottles connected by two 250ml single-port bottles to form an A bottle and a B bottle respectively, baking at 120 ℃ for 3 hours, while the bottle is hot, connecting the A, B bottle to a vacuum tube, introducing argon, vacuumizing, baking by an alcohol lamp while pumping, cooling, introducing argon, repeating for three times, adding 2.32g glycolide into the B bottle under the argon atmosphere, adding stirring magnetons into the A, B bottles respectively, adding 15ml Tetrahydrofuran (THF) into the A bottle under the ice water bath condition, adding 1.4ml of initiator (N, N-dimethylethanolamine sodium) and 5ml of ethylene oxide into the A bottle, stirring for 24 hours in the ice water bath, stirring for 12 hours at room temperature to form brownish red viscous liquid, and extracting reaction liquid (PEG) to measure M n =2500, quickly pouring into a B bottle, stirring at room temperature for 1.5-2 h, then adding 0.75g of butanesultone, stirring at room temperature for 6h, adding 1ml of methanol, stirring for 30 min, stopping the reaction, adding 1ml of 1m HCl, 2ml of ultrapure water, stirring for 2h, pouring into an absolute ethanol solution, suction-filtering to obtain a white viscous solid, and drying in a vacuum drying oven for 24h to obtain a white powdery solid with the yield of 93.9%. GPC: m is M n ＝5000，PDI＝1.2。
Example 12
The preparation method of the block copolymer (S-PEG-b-PGA 4) containing the sulfobetaine end group comprises the following steps:
adopting two double-connection single-port bottles connected by two 250ml single-port bottles to form an A bottle and a B bottle respectively, baking at 120 ℃ for 3 hours, while the bottle is hot, connecting the A, B bottle to a vacuum tube, introducing argon, vacuumizing, baking by an alcohol lamp while pumping, cooling, introducing argon, repeating for three times, adding 2.32g glycolide into the B bottle under the argon atmosphere, adding stirring magnetons into the A, B bottles respectively, adding 15ml Tetrahydrofuran (THF) into the A bottle under the ice water bath condition, adding 0.7ml of initiator (N, N-dimethylethanolamine sodium) and 5ml of ethylene oxide into the A bottle, stirring for 24 hours in the ice water bath, stirring for 12 hours at room temperature to form brownish red viscous liquid, and extracting reaction liquid (PEG) to measure M n =5000, rapidly pouring into a B bottle, stirring at room temperature for 1.5-2 h, then adding propane sultone 0.75g, stirring at room temperature for 6h, adding 1ml methanol, stirring for 30 min, stopping the reaction, adding 1m HCl 1ml,2ml ultra-pure water, stirring for 2h, pouring into an absolute ethanol solution, suction-filtering to obtain a white viscous solid, and drying in a vacuum drying oven for 24h to obtain a white powdery solid with a yield of 94.1%. GPC: m is M n ＝10000，PDI＝1.2。
The present invention is not limited to the above-described specific embodiments, and various modifications may be made by those skilled in the art without inventive effort from the above-described concepts, and are within the scope of the present invention.

Claims (8)

1. A polyethyleneglycol-polyester block copolymer containing sulfobetaine end groups, which is characterized by having a general structure of the following formula (1):
Figure FDA0003871595220000011
wherein x is an integer of 10 to 5000 and y is an integer of 10 to 5000; r is R 1 is-CH 3 、-CH 2 CH 3 or-CH (CH) 3 ) 2 ；R 2 A linear alkylene group having 3 to 8 carbon atoms; r is R 3 is-CH 2 -、-CH(CH 3 ) -or- (CH) 2 ) 5 -。
2. A process for the preparation of a polyethyleneglycol-polyester block copolymer containing sulfonic acid betaine end groups according to claim 1, comprising the steps of:
s1, performing electrophilic substitution reaction on N, N-dialkylethanolamine containing hydroxyl end groups and a metal organic compound to obtain an anionic polymerization initiator;
s2, carrying out anionic polymerization reaction on the obtained anionic polymerization initiator, ethylene oxide and epoxy ester monomers to obtain a polyethylene glycol-polyester block copolymer with N, N-dialkylamino end groups;
s3, carrying out ring-opening reaction on the obtained polyethylene glycol-polyester block copolymer with the N, N-dialkyl amino end group and sultone to obtain the polyethylene glycol-polyester block copolymer with the sultaine end group.
3. The method for preparing a polyethyleneglycol-polyester block copolymer containing end groups of sulfobetaine according to claim 2, wherein in the step S2, the raw material addition sequence of the anionic polymerization reaction is as follows: sequentially adding ethylene oxide and epoxy ester monomers into the obtained anionic polymerization initiator.
4. The method for preparing a polyethyleneglycol-polyester block copolymer containing end groups of sulfobetaine according to claim 2, wherein in the step S3, the conditions of the ring-opening reaction are as follows: the reaction temperature is between-10 and 100 ℃ and the reaction time is between 2 and 24 hours.
5. The method for preparing a polyethyleneglycol-polyester block copolymer containing sulfonic acid betaine end groups according to claim 2, wherein the metal organic compound is any one of potassium hydroxide, potassium naphthalene, potassium benzhydryl, potassium tert-butoxide, sodium hydroxide, sodium naphthalene, sodium benzhydryl and sodium tert-butoxide.
6. The method for preparing a polyethyleneglycol-polyester block copolymer containing sulfobetaine end groups according to claim 2, wherein the epoxy ester monomer is one or a combination of more than two of glycolide, lactide and caprolactone.
7. The method for preparing a polyethyleneglycol-polyester block copolymer containing the terminal end of sulfobetaine according to claim 2, wherein the sultone is any one of propane sultone, butane sultone, pentane sultone, hexane sultone, heptane sultone and octane sultone.
8. The method for preparing a polyethyleneglycol-polyester block copolymer containing sulfonic acid betaine end groups according to claim 2, wherein in the step S3, the progress of the ring-opening reaction is terminated by a terminator, and the terminator is any one of alcohols, acids, amines and water.
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