Polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer and preparation method and application thereof

Abstract

The present invention belongs to the technical field of polymer synthesis, and in particular to a kind of polyethylene glycol monomethyl ether itaconic acid polyester polyethylene glycol monomethyl ether amphiphilic block copolymer and its preparation method and application. The present invention uses the purification of commercial 1,1,3,3-tetramethylguanidine, synthesizes itaconic acid polyester by adding dibasic halide and itaconic acid monomer, and then reacts itaconic acid polyester with carboxylic acid-terminated polyethylene glycol monomethyl ether and controls the reaction time. The reaction conditions are mild, and no protective gas is needed to successfully prepare an amphiphilic triblock copolymer with a narrow molecular weight distribution (D < 1.26) and controllable structure, i.e., polyethylene glycol monomethyl ether itaconic acid polyester polyethylene glycol monomethyl ether amphiphilic block copolymer. Utilizing the synthesized amphiphilic triblock copolymer, the present invention also self-assembles the self-assembled structure of more than 95% of nano micelles. The synthetic method of the present invention is simple and feasible to operate, and raw materials are cheap and easy to obtain, with certain economic benefits.

Description

Technical Field

[0001] The invention belongs to the technical field of polymer synthesis, and particularly relates to a polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer and a preparation method and application thereof. Background Art

[0002] Block copolymers generally refer to linear polymers composed of two homopolymers of different compositions linked by chemical bonds, combining the properties of both homopolymers. Compared to linear homopolymers, block copolymers possess many unique properties and are widely used in surfactants, emulsifiers, compatibilizers, nanomedicine, and other fields. Polyethylene glycol (PEG) has a wide molecular weight range, a wide selection, is non-toxic, has good hydrophilicity, and is non-antigenic and non-immunogenic. It has been approved by the US Federal Drug Administration (FDA) for human use and is widely used in biomedical materials. Itaconic acid is present in mammalian macrophages and is a metabolite with important immunoregulatory functions, making it a potential therapeutic target for a variety of diseases. Furthermore, itaconic acid is an endogenous metabolite produced by cells, making it a potential drug candidate without causing serious side effects. Itaconic acid also exhibits excellent anti-inflammatory, antibacterial, and antiviral effects. Polyester is a well-known biodegradable polymer with excellent processability, low cytotoxicity, and drug penetrance, leading to its widespread use in gene delivery, tissue engineering scaffolds, and marine antifouling materials.

[0003] Polyethylene glycol monomethyl ether-itaconyl polyester-polyethylene glycol monomethyl ether (mPEG-DHB-ITA-mPEG) possesses unique properties such as hydrophilicity, flexibility, biodegradability, cell affinity, and antibacterial properties. Based on the condensation polymerization method for synthesizing polyesters, the synthesis of poly(ethylene glycol) monomethyl ether-itaconyl polyester-poly(ethylene glycol) monomethyl ether) triblock copolymers typically involves transesterification of dimethyl itaconate with a polyol to produce an itaconyl polyester. Block copolymers are then prepared by esterification of the terminal carboxyl groups of the modified polyethylene glycol (PEG) with the hydroxyl groups of the itaconyl polyester. This method offers a wider range of monomer options, allowing the synthesis of a wider range of polyester block copolymers. However, these polyesters typically require high polymerization conditions, such as high temperature and high pressure. Furthermore, the molecular weight of the resulting polymers is not easily controllable, and the molecular weight distribution is generally broad. In addition, the reaction of the terminal carboxyl group of polyethylene glycol (PEG) with the terminal hydroxyl group of polyester is also an esterification reaction. The preparation of high molecular weight copolymers also needs to be carried out at a relatively high temperature. During this process, side reactions such as transesterification may occur, resulting in changes in the polymer structure. In the field of biomedicine, especially for controlled drug release, block copolymers are required to have a clear molecular weight and a narrow molecular weight distribution. Therefore, when synthesizing novel polyethylene glycol monomethyl ether-itaconyl polyester-polyethylene glycol monomethyl ether triblock copolymers, it is necessary to improve the above-mentioned synthesis method. Summary of the Invention

[0004] In view of the defects and shortcomings in the prior art, the primary purpose of the present invention is to provide a method for preparing a structure-controllable polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer.

[0005] Another object of the present invention is to provide a polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether amphiphilic triblock copolymer with narrow molecular weight distribution prepared by the above preparation method.

[0006] Another object of the present invention is to provide an application of the above-mentioned polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether amphiphilic triblock block copolymer.

[0007] To achieve the above-mentioned purpose, the present invention is implemented through the following technical solutions:

[0008] A method for preparing a polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer comprises the following steps:

[0009] Itaconic acid, 1,1,3,3-tetramethylguanidine, a dibasic halide, and a solvent are mixed and heated, and after the reaction is complete, polyethylene glycol monomethyl ether with a single carboxyl end is added to continue the reaction, and after the reaction is completed, precipitation, dialysis, and drying are performed to obtain a polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer;

[0010] The molar ratio of itaconic acid, dibasic halide, 1,1,3,3-tetramethylguanidine and polyethylene glycol monomethyl ether is 1-3:2-6:1.5-3.5:1-3.

[0011] Preferably, the reaction equation for preparing the polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer is shown in Formula 1 below:

[0012]

[0013] In formula 1, 46 is the degree of polymerization of polyethylene glycol monomethyl ether, and n is the degree of polymerization of itaconic acid-based polyester in the final block polymer.

[0014] The present invention uses the purification of commercial 1,1,3,3-tetramethylguanidine, synthesizes itaconic acid-based polyester by adding dibasic halide and itaconic acid monomer, and then reacts the itaconic acid-based polyester with carboxylic acid-terminated polyethylene glycol monomethyl ether and controls the reaction time. The reaction conditions are mild and no protective gas is required to successfully prepare a polymer with a narrow molecular weight distribution. The structure-controllable amphiphilic triblock copolymer, namely polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer, utilizes the synthesized amphiphilic triblock copolymer to self-assemble more than 95% of the nano micelles.

[0015] The present invention primarily utilizes the click chemistry reaction between carboxylic acids and halogens. Under the action of tetramethylguanidine, the carboxylic acid first forms a carboxylate anion, which then only contributes to the α-carbon of the halide. Simultaneously with the formation of the ester group, the halogen atom is removed and reacts with tetramethylguanidine to form the corresponding tetramethylguanidine hydrogen halide salt. The characteristics of click chemistry enable a mild reaction and eliminate the need for protective gas. By controlling the different carboxylic acid and halogen structures, structural control is achieved.

[0016] Preferably, the 1,1,3,3-tetramethylguanidine is purified before use.

[0017] As a further preference, the 1,1,3,3-tetramethylguanidine is purified twice before use and stored in an argon atmosphere.

[0018] As a further preference, the purification step comprises: stirring with calcium hydride (CaH2) overnight, and then purifying by reduced pressure distillation.

[0019] Preferably, the dihalide is any one of 1,4-dibromobutane, 1,6-dibromohexane, 1,4-dichlorobutane and 1,4-dichlorohexane.

[0020] Preferably, the solvent is any one or more of dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, methyltetrahydrofuran, toluene, benzene, acetonitrile and dioxane.

[0021] Preferably, the molecular weight of the polyethylene glycol monomethyl ether is M n =2000,

[0022] Preferably, the reaction time during the process of mixing itaconic acid, 1,1,3,3-tetramethylguanidine, dihalide and solvent and heating is 3 to 24 hours.

[0023] Preferably, the heating reaction temperature is 10-70°C.

[0024] Preferably, the reaction time after adding the polyethylene glycol monomethyl ether having a single carboxyl terminal is 6 to 24 hours.

[0025] The polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer prepared by the preparation method described above.

[0026] The above-mentioned polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer is used in the fields of drug transport and release, nanoreactor and nanocatalysis.

[0027] Therefore, the present invention has the following beneficial effects:

[0028] The present invention uses the purification of commercial 1,1,3,3-tetramethylguanidine, synthesizes itaconic acid-based polyester by adding dibasic halide and itaconic acid monomer, and then reacts the itaconic acid-based polyester with carboxylic acid-terminated polyethylene glycol monomethyl ether and controls the reaction time. The reaction conditions are mild and no protective gas is required to successfully prepare a polymer with a narrow molecular weight distribution. The present invention discloses a structurally controllable amphiphilic triblock copolymer, namely, a polyethylene glycol monomethyl ether-itaconyl polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer. Using the synthesized amphiphilic triblock copolymer, the present invention also self-assembles over 95% of the nanomicelles. The synthesis method of the present invention is simple and feasible, and the raw materials are readily available and inexpensive, resulting in considerable economic benefits. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 This is the H NMR spectrum of the polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer in Example 1.

[0030] Figure 2 This is the infrared spectrum of the polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer in Example 1. DETAILED DESCRIPTION

[0031] The present invention will be further described below in conjunction with the accompanying drawings and specific embodiments. Those skilled in the art will be able to implement the present invention based on these descriptions. Furthermore, the embodiments of the present invention described below are generally only a portion of the embodiments of the present invention, rather than all of the embodiments. Therefore, all other embodiments derived by those skilled in the art based on the embodiments of the present invention without inventive effort should fall within the scope of protection of the present invention.

[0032] Example 1

[0033] This embodiment provides a method for preparing a polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer.

[0034] A method for preparing a polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer comprises the following steps:

[0035] (S.1) Weigh 130 mg (1 mmol) of itaconic acid (ITA) into a sample vial and react at room temperature (25°C). Then, add 5 mL of dimethylformamide (DMF) until the itaconic acid is completely dissolved. Add 230 mg (2 mmol) of 1,1,3,3-tetramethylguanidine (TMG) as a catalyst. After the exotherm ends, add 448 mg (2 mmol) of 1,6-dibromohexane dropwise using a constant pressure funnel to continue the reaction. After 12 hours of reaction, add 2 g (1 mmol) of polyethylene glycol monomethyl ether carboxylate (mPEG-COOH2000) and continue the reaction for another 12 hours to obtain a reaction mixture.

[0036] (S.2) The reaction mixture obtained in step (S.1) was precipitated with glacial ether, dialyzed in water, and freeze-dried to obtain a light yellow solid, which is polyethylene glycol monomethyl ether-itaconyl polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer (mPEG-DHB-ITA-mPEG), and the product was analyzed by nuclear magnetic resonance and gel permeation chromatography (GPC). The nuclear magnetic hydrogen spectrum of the polyethylene glycol monomethyl ether-itaconyl polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer in this embodiment is as follows: Figure 1 As shown. Among them, Figure 1In the figure: a represents the methoxy group at the end of the mPEG block, b represents the methylene group on the PEG main chain, c represents the methylene group at the end of the mPEG, d and e represent the double bond of the itaconic acid polyester side chain, f represents the methylene group connected to the double bond, g and l represent the methylene group connected to the ester group, and h, i, j, and k represent the individual methylene groups on the main chain. The infrared spectrum of the polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer in this example is shown in FIG. Figure 2 The H NMR and IR spectra of the polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer are as follows: 1HNMR (CDCl3, 400 MHz), chemical shift δ (ppm): ~6.31 ppm. ~5.70 ppm (-C=CH2, on the itaconic acid polyester side chain), ~4.17 ppm (-COOCH2-, on the itaconic acid polyester main chain), 4.09 ppm (-CH2-OOC-itaconic acid polyester main chain), 3 .67ppm (-CH2-O, on the mPEG main chain), 3.64ppm (-O-CH2-, on the mPEG main chain), 3.38ppm (-C-CH2-COO, on the itaconic acid polyester main chain), 3.33ppm (CH3-, methoxy group at the end of mPEG), 2.28ppm (-CH2-COO), methylene group at the end of the mPEG main chain), ~1.69ppm.1.64ppm.1.42ppm. (-CH2-, on the itaconic acid polyester main chain).

[0037] FTIR(KBr):~1731cm -1 (-C=O, on the itaconate polyester backbone), ~1125cm -1 (-CO-, on the PEG main chain), ~2923cm -1 、~2860cm -1 (-CH3, -CH2-).

[0038] Examples 2 to 5

[0039] A series of amphiphilic block copolymers of polyethylene glycol monomethyl ether (mPEG)-itaconic acid-based polyester (mPEG)-mPEG (mPEG-DHB-ITA-mPEG) were designed and designated A2, A3, A4, and A5. Specifically, A2, A3, A4, and A5 were all mPEG-DHB-ITA-mPEG, with a number-average molecular weight of PEG of 2000. The synthesis methods in Examples 2-5 were the same as in Example 1, except that the reaction times during the mixing and heating of itaconic acid, 1,1,3,3-tetramethylguanidine, 1,6-dibromohexane, and DMF solvent varied: 3 h, 6 h, 12 h, and 24 h, respectively. The raw material ratios and reaction times for each polymer are shown in Table 1.

[0040] Table 1: Raw material ratios, polymer molecular weights, and molecular weight distributions of a series of polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether (mPEG-DHB-ITA-mPEG) amphiphilic block copolymers

[0041]

[0042] From the data analysis in Table 1, it can be seen that the molecular weight distribution of the prepared amphiphilic block copolymers is relatively narrow. As the reaction time increases, the molecular weight increases accordingly, thus achieving the purpose of the present invention.

[0043] Example 6

[0044] This example provides a method for preparing a polyethylene glycol monomethyl ether-itaconate polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer (mPEG-DHB-ITA-mPEG), which is recorded as polymer A6.

[0045] The difference between this embodiment and embodiment 1 is that:

[0046] A method for preparing a polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer, wherein 115 mg (1 mmol) of 1,1,3,3-tetramethylguanidine (TMG) is added in step (S.1) to replace 230 mg (2 mmol) of 1,1,3,3-tetramethylguanidine (TMG). Other conditions are the same as those in Example 1. The number average relative molecular weight Mn of the polymer A6 finally prepared is 13500 g / mol, and the molecular weight dispersion is is 1.25, indicating that the purpose of our invention can be achieved under this condition.

[0047] Example 7

[0048] This example provides a method for preparing a polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer (mPEG-DHB-ITA-mPEG), which is recorded as polymer A7.

[0049] The difference between this embodiment and embodiment 1 is that:

[0050] A method for preparing a polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer, wherein 345 mg (3 mmol) of 1,1,3,3-tetramethylguanidine (TMG) is added in step (S.1) to replace 230 mg (2 mmol) of 1,1,3,3-tetramethylguanidine (TMG). Other conditions are the same as those in Example 1. The number average relative molecular weight Mn of the polymer A7 finally prepared is 12560 g / mol, and the molecular weight dispersion is 1. It is 1.52, indicating that excess catalyst will broaden the D of the polymer.

[0051] Example 8

[0052] This example provides a method for preparing a polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer (mPEG-DHB-ITA-mPEG), which is recorded as polymer A8.

[0053] The difference between this embodiment and embodiment 1 is that:

[0054] A method for preparing a polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer, wherein in step (S.1), 5 mL of purified tetrahydrofuran (THF) is used instead of 5 mL of dimethylformamide (DMF) as the solvent. All other conditions are the same as in Example 1. The number average relative molecular weight Mn of the polymer A8 finally prepared is 8460 g / mol. It is 1.21, indicating that using THF as the reaction solvent will reduce the reaction rate.

[0055] Example 9

[0056] This example provides a method for preparing a polyethylene glycol monomethyl ether-itaconate polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer (mPEG-DHB-ITA-mPEG), which is recorded as polymer A9.

[0057] The difference between this embodiment and embodiment 1 is that:

[0058] A method for preparing a polyethylene glycol monomethyl ether-itaconyl polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer, wherein in step (S.1), 5 mL of purified dimethyl sulfoxide (DMSO) is used instead of 5 mL of dimethylformamide (DMF) as the solvent. All other conditions are the same as in Example 1. The resulting polymer A9 has a number average relative molecular weight Mn of 13670 g / mol and a D of 1.19, demonstrating that the invention can be achieved using DMSO as the reaction solvent.

[0059] Example 10

[0060] This example provides a method for preparing a polyethylene glycol monomethyl ether-itaconate polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer (mPEG-DHB-ITA-mPEG), which is recorded as polymer A10.

[0061] The difference between this embodiment and embodiment 1 is that:

[0062] A method for preparing a polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer, wherein in step (S.1), "the reaction temperature is raised from room temperature to 40°C" replaces "reacting at room temperature (25°C)". All other steps are the same as in Example 1. The number average relative molecular weight Mn of the finally prepared polymer A10 is 12300 g / mol. It is 1.25, indicating that the reaction temperature of 40°C can also achieve our invention purpose.

[0063] Example 11

[0064] This example provides a method for preparing a polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer (mPEG-DHB-ITA-mPEG), which is recorded as polymer A11.

[0065] The difference between this embodiment and embodiment 1 is that:

[0066] A method for preparing a polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer, wherein in step (S.1), "reacting at room temperature (25°C)" is replaced by "reacting at room temperature (25°C)" All other steps are the same as in Example 1. The resulting polymer A11 has a number average relative molecular weight Mn of 7980 g / mol and a D of 1.29, indicating that a reaction temperature of 10°C reduces the reaction rate.

[0067] Example 12

[0068] This example provides a method for preparing a polyethylene glycol monomethyl ether-itaconate polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer (mPEG-DHB-ITA-mPEG), which is recorded as polymer A12.

[0069] The difference between this embodiment and embodiment 1 is that:

[0070] A method for preparing a polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer, wherein in step (S.1), "the reaction temperature is raised from room temperature (25°C) to 70°C" replaces "reacting at room temperature (25°C)". All other steps are the same as in Example 1. The number average relative molecular weight Mn of the finally prepared polymer A12 is 12650 g / mol. is 1.65, indicating that the reaction temperature of 70°C is not suitable for the present invention.

[0071] Example 13

[0072] This example provides a method for preparing a polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer (mPEG-DHB-ITA-mPEG), which is recorded as polymer A13.

[0073] The difference between this embodiment and embodiment 1 is that:

[0074] A method for preparing a polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer, wherein, in step (S.1), 130 mg (1 mmol) of itaconic acid (ITA) is weighed; 173 mg (1.5 mmol) of 1,1,3,3-tetramethylguanidine (TMG) is added; and 448 mg (2 mmol) of 1,6-dibromohexane is added dropwise to react. After reacting for 12 hours, 2 g (1 mmol) of polyethylene glycol monomethyl ether carboxyl (mPEG-COOH2000) is added and the reaction is continued for 12 hours to obtain a reaction mixed solution. The rest is the same as in Example 1. The number average relative molecular weight Mn of the polymer A13 finally prepared is 12890 g / mol, It is 1.26, indicating that the purpose of our invention can be achieved under this condition.

[0075] Example 14

[0076] This example provides a method for preparing a polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer (mPEG-DHB-ITA-mPEG), which is recorded as polymer A14.

[0077] The difference between this embodiment and embodiment 1 is that:

[0078] A method for preparing a polyethylene glycol monomethyl ether-itaconic acid-based polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer, wherein, in step (S.1), 390 mg (3 mmol) of itaconic acid (ITA) is weighed; 402 mg (3.5 mmol) of 1,1,3,3-tetramethylguanidine (TMG) is added; and 1.344 g (6 mmol) of 1,6-dibromohexane is added dropwise to react. After reacting for 12 hours, 6 g (3 mmol) of polyethylene glycol monomethyl ether carboxyl (mPEG-COOH2000) is added and the reaction is continued for 12 hours to obtain a reaction mixed solution. The rest is the same as in Example 1. The number average relative molecular weight Mn of the polymer A14 finally prepared is 12760 g / mol, is 1.31, and under this condition, our invention purpose can also be achieved.

[0079] Example 15

[0080] This embodiment provides an application of a polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer in the fields of drug transport and release, nanoreactors, and nanocatalysis.

[0081] In this example, polyethylene glycol monomethyl ether-itaconyl polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer A3 was prepared according to the synthesis method of Example 3. Further investigation of its self-assembly behavior in aqueous solution revealed that 95% of the polymer assembled into nanomicelles with a size of 200 nm.

[0082] Comparative Example 1

[0083] This comparative example provides a method for preparing a polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer (mPEG-DHB-ITA-mPEG), which is recorded as polymer A15.

[0084] The difference between this comparative example and Example 1 is:

[0085] A method for preparing a polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer, wherein the reaction time in step (S.1) is 1 hour, and the other conditions are the same as in Example 1. The number average relative molecular weight Mn of the polymer A15 finally prepared is 3980 g / mol, It is 1.20, indicating that the reaction time is too short and the reaction degree is low, which does not meet the experimental requirements.

[0086] Comparative Example 2

[0087] This comparative example provides a method for preparing a polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer (mPEG-DHB-ITA-mPEG), which is recorded as polymer A16.

[0088] The difference between this comparative example and Example 1 is:

[0089] A method for preparing a polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer, wherein the reaction time in step (S.1) is 36 hours, and the other conditions are the same as in Example 1. The number average relative molecular weight Mn of the polymer A16 finally prepared is 13250 g / mol, is 2.36, indicating that the block polymer obtained by the reaction time is too long Too large and not suitable for the present invention.

[0090] Comparative Example 3

[0091] This comparative example provides a method for preparing a polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer (mPEG-DHB-ITA-mPEG), which is recorded as polymer A17.

[0092] The difference between this comparative example and Example 1 is:

[0093] A method for preparing a polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer, wherein in step (S.1), "reacting at room temperature (25°C)" is replaced by "reaction temperature reduced from room temperature to 0°C." All other conditions are the same as in Example 1. The resulting polymer A17 has a number average relative molecular weight Mn of 5300 g / mol and a D of 1.21, indicating that the reaction temperature of 0°C is too low, resulting in a relatively slow reaction, and these reaction conditions cannot achieve the purpose of the invention.

[0094] Comparative Example 4

[0095] This comparative example provides a method for preparing a polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer (mPEG-DHB-ITA-mPEG), which is recorded as polymer A18.

[0096] The difference between this comparative example and Example 1 is:

[0097] A method for preparing a polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer, wherein in step (S.1), "the reaction temperature is increased from room temperature to 120°C" replaces "reacting at room temperature (25°C)". All other steps are the same as in Example 1. The number average relative molecular weight Mn of the finally prepared polymer A18 is 12700 g / mol. is 2.51, indicating that the reaction temperature of 120°C is too high. If the reaction temperature is too high, the reaction conditions cannot achieve the purpose of our invention.

[0098] The above description is only a detailed description of the preferred embodiments and principles of the present invention. For ordinary technicians in this field, based on the ideas provided by the present invention, there may be changes in the specific implementation methods, and these changes should also be considered as the scope of protection of the present invention.

Claims

1. A method for preparing a polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer, characterized in that: The method comprises the following steps: mixing itaconic acid, 1,1,3,3-tetramethylguanidine, a dibasic halide and a solvent and heating the mixture; adding polyethylene glycol monomethyl ether with a single carboxyl end and continuing the reaction after the reaction is complete; and performing precipitation, dialysis and drying after the reaction is complete to obtain a polyethylene glycol monomethyl ether itaconic acid-based polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer; the molar ratio of the itaconic acid, the dibasic halide, the 1,1,3,3-tetramethylguanidine and the polyethylene glycol monomethyl ether is 1-3:2-6:1.5-3.5:1-3; and during the process of mixing and heating the itaconic acid, the 1,1,3,3-tetramethylguanidine, the dibasic halide and the solvent, the heating reaction temperature is 10-70°C and the reaction time is 3-24 hours.

2. The method for preparing the polyethylene glycol monomethyl ether-itaconyl polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer according to claim 1, characterized in that: The 1,1,3,3-tetramethylguanidine is purified before use.

3. The method for preparing the polyethylene glycol monomethyl ether-itaconyl polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer according to claim 1, wherein: The dibasic halide is any one of 1,4-dibromobutane, 1,6-dibromohexane, 1,4-dichlorobutane and 1,4-dichlorohexane.

4. The method for preparing the polyethylene glycol monomethyl ether-itaconyl polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer according to claim 1, wherein: The solvent is any one or more of dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, methyltetrahydrofuran, toluene, benzene, acetonitrile and dioxane.

5. The method for preparing the polyethylene glycol monomethyl ether-itaconyl polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer according to claim 1, characterized in that: The molecular weight of the polyethylene glycol monomethyl ether is Mn=2000, and D=1.

03.

6. The method for preparing the polyethylene glycol monomethyl ether-itaconyl polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer according to claim 1, characterized in that: The reaction time after adding polyethylene glycol monomethyl ether having a single carboxyl terminal is continued for 6 to 24 hours.

7. The polyethylene glycol monomethyl ether-itaconate polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer prepared by the preparation method according to any one of claims 1 to 6.

8. Use of the polyethylene glycol monomethyl ether-itaconic acid polyester-polyethylene glycol monomethyl ether amphiphilic block copolymer according to claim 7 in the fields of nanoreactors and nanocatalysis.

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