Polypeptide ester ether amine random polymers and methods for their preparation and use

Abstract

Polypeptide ester ether amine random polymers and methods for their preparation are provided. [Solution] The polypeptide ester ether amine random polymer of the present invention is a random copolymer of an amino acid monomer and an alkylene oxide. In this invention, copolymerization of an amino acid monomer and an alkylene oxide monomer is achieved by a one-step method using a mixed monomer mixture using a transition metal or rare earth metal salt as a catalyst. The random copolymerization product has controllable molecular weight, narrow molecular weight distribution, and adjustable copolymer composition. Furthermore, the random copolymerization product has excellent solubility, biodegradability, easy functionalization, excellent processability, and excellent biocompatibility, making it promising for future applications in the biomedical field.

Description

[Technical Field]

[0001] The present invention relates to the technical field of preparation of medical polymeric materials, in particular to polypeptide ester ether amine random polymers, and their preparation methods and uses. [Background technology]

[0002] The structural unit of poly(α-amino acid) (PAA) is an α-amino acid residue, which is identical or similar to the α-amino acid repeating unit structure of in vivo protein peptide chains. This structure is highly biocompatible and can be used as a biomedical polymer material. The commonly used method for synthesizing poly(α-amino acid)s is the ring-opening polymerization of α-amino acid-N-carboxylic anhydrides (NCAs) (Chem. Soc. Rev., 2013, 42, 7373-7390). Currently, random copolymerization of amino acid-based monomers has primarily focused on copolymerization with different amino acid monomers, with no reports on random copolymerization with other non-nitrogen-based monomers. Consequently, the main chains of the copolymerized products are all linked by rigid amide bonds (peptide bonds), limiting the possibility of structural design for specific applications. The only reported polymerization of lactide and γ-benzylglutamate-NCA mixed monomers also showed that the two monomers polymerized independently and sequentially to produce a block polymer rather than a random polymer (Macromolecules 2024, 57, 5691-5701).

[0003] Alkylene oxides are common industrial products and basic raw materials for epoxy resins, widely used in binders, coatings, and composite materials. Alkylene oxides are versatile, inexpensive, and easily functionalized, making them excellent copolymerizable monomers. However, there have been no reports on the copolymerization of amino acid-based monomers with alkylene oxides. This is primarily due to the significant difference in activity between the nitrogen-terminated chain growth centers generated during the polymerization of amino acid-based monomers and the oxygen-terminated centers of non-nitrogen-based monomers, making random copolymerization difficult. Summary of the Invention [Problem to be solved by the invention]

[0004] This invention addresses the difficulty of polymerizing amino acid-based monomers and non-nitrogen-based monomers, and proposes for the first time a polypeptide ester ether amine polymer obtained by random copolymerization of amino acid-based monomers and alkylene oxides. This copolymer has advantages such as controllable molecular weight, narrow molecular weight distribution, excellent solubility, biodegradability, easy functionalization, excellent processability, and excellent biocompatibility. [Means for solving the problem]

[0005] To achieve the above objectives, the technical solutions adopted by the present invention are as follows:

[0006] The polypeptide ester ether amine random polymers have the following general structural formula: [ka] (wherein R1 and R2 are independently any one selected from the group consisting of hydrogen, a C1-C12 saturated aliphatic hydrocarbon group, a C1-C12 unsaturated aliphatic hydrocarbon group, an aromatic hydrocarbon group, an alkyl ether group, a hydroxyalkyl group, a C1-C6 hydroxyalkyl group having a protected hydroxy group, a hydroxybenzyl group having a protected hydroxy group, an alkyl sulfide group, an alkylindolyl group, a C1-C6 carboxyalkyl group having a protected carboxy group, and a C1-C6 aminealkyl group having a protected amine group; or R1 and R2 together represent any one of tetrahydropyrrole, and the substituent is hydroxytetrahydropyrrole having a protected hydroxy group; R3 and R4 are independently any one selected from hydrogen, a C1 to C9 saturated aliphatic hydrocarbon group, and a C1 to C9 unsaturated aliphatic hydrocarbon, or R3 and R4 together form one of cyclohexane, methyl group, ethyl group, or vinyl group-substituted cyclohexane, x is selected from 0.30 to 0.99, and n is selected from 10 to 500.

[0007] In some embodiments, the polypeptide ester ether amine random polymer has a number average molecular weight of 1 to 100 kg / mol and a molecular weight distribution of 2.0 or less. In some embodiments, the polypeptide ester ether amine random polymer has a number average molecular weight of 1 to 50 kg / mol.

[0008] The random copolymer provided by the present invention simultaneously has amide bonds (peptide bonds), ester bonds, ether bonds, and amine groups in the main chain, which can improve the copolymer's properties such as water solubility, biodegradability, and biocompatibility. The structure can be easily functionalized, the molecular weight can be controlled, the molecular weight distribution is narrow, and the copolymer composition can be adjusted. Through structural design, copolymers that meet the needs of various scenarios can be obtained.

[0009] The present invention also provides a method for producing the polypeptide ester ether amine random polymer by solution polymerization of a raw material containing an α-amino acid-N-carboxylic acid anhydride monomer and an alkylene oxide monomer using ML as a catalyst, The present invention provides a method for preparing the polypeptide ester ether amine random polymer, wherein M in the catalyst ML is a transition metal or rare earth metal element, and L is one or more of trifluoromethanesulfonate, p-toluenesulfonate, chlorine, bromine, iodine, trifluoroacetate, and acetate. This invention achieves the random copolymerization of α-amino acid-N-carboxylic anhydride monomers and alkylene oxides using transition metal or rare earth metal salts as catalysts. However, transition metal salts cannot directly catalyze the polymerization of amino acid-N-carboxylic anhydride monomers; the copolymerization of both must proceed smoothly in the presence of alkylene oxide. This method avoids multi-step reactions by introducing ester bonds, ether bonds, and amine groups into polyamides, providing a novel and simple synthetic method for functionalizing polyamides. This method is versatile and applicable to a variety of α-amino acid-N-carboxylic anhydride monomers and alkylene oxides.

[0010] Research has shown that various substituents without active hydrogen atoms contained in α-amino acid-NCA monomers, such as alkyl groups, aromatic groups, ethers, thioethers, amide groups, and ester groups, have little effect on the performance of the five-membered ring ring-opening polymerization reaction in the monomer structure, and therefore all α-amino acid-NCA monomers having such various substituents are suitable for the polymerization reaction system of the present invention. In some embodiments, the structure of the α-amino acid-N-carboxylic acid anhydride monomer is represented by formula (I-1), and the structural formula of the alkylene oxide monomer is represented by formula (I-2). [ka] (wherein R1 and R2 are independently any one selected from the group consisting of hydrogen, a C1-C12 saturated aliphatic hydrocarbon group, a C1-C12 unsaturated aliphatic hydrocarbon group, an aromatic hydrocarbon group, an alkyl ether group, a hydroxyalkyl group, a C1-C6 hydroxyalkyl group having a protected hydroxy group, a hydroxybenzyl group having a protected hydroxy group, an alkylsulfide group, an alkylindolyl group, a C1-C6 carboxyalkyl group having a protected carboxy group, and a C1-C6 aminealkyl group having a protected amine group; or R1 and R2 are jointly any one of tetrahydropyrrole, and the substituent is hydroxytetrahydropyrrole having a protected hydroxy group; R3 and R4 are independently any one selected from hydrogen, a C1-C9 saturated aliphatic hydrocarbon group, and a C1-C9 unsaturated aliphatic hydrocarbon, or R3 and R4 together form one of cyclohexane, cyclohexane substituted with a methyl group, an ethyl group, or a vinyl group.

[0011] In some embodiments, the α-amino acid-N-carboxylic acid anhydride monomer comprises one or more of sarcosine-NCA, N-substituted glycine-NCA, ε-benzyloxycarbonyl lysine-NCA, ε-trifluoroacetyl lysine-NCA, γ-methyl glutamate-NCA, γ-ethyl glutamate-NCA, γ-benzyl glutamate-NCA, β-benzyl aspartate-NCA, phenylalanine-NCA, valine-NCA, leucine-NCA, isoleucine-NCA, methionine-NCA, tert-butylserine-NCA, alanine-NCA, glycine-NCA, tryptophan-NCA, proline-NCA, threonine-NCA, O-acetylhydroxyproline-NCA, O-benzyltyrosine-NCA, O-benzyllevodopa-NCA, etc.

[0012] In some embodiments, the structure of the N-substituted glycine-NCA is represented by formula (I-3): [ka] (Here, R5 is selected from a C2 to C12 saturated aliphatic hydrocarbon group, a C2 to C12 unsaturated aliphatic hydrocarbon group, an aromatic hydrocarbon group, an alkyl ether group, an alkyl sulfide group, a C1 to C6 carboxyalkyl group in which the carboxy group is protected, and a C1 to C6 aminealkyl group in which the amino group is protected.)

[0013] The structural formulas of sarcosine-NCA, ε-benzyloxycarbonyllysine-NCA, ε-trifluoroacetyllysine-NCA, γ-methylglutamate-NCA, γ-ethylglutamate-NCA, γ-benzylglutamate-NCA, β-benzylaspartate-NCA, phenylalanine-NCA, valine-NCA, leucine-NCA, isoleucine-NCA, methionine-NCA, tert-butylserine-NCA, alanine-NCA, glycine-NCA, tryptophan-NCA, proline-NCA, threonine-NCA, O-acetylhydroxyproline-NCA, O-benzyltyrosine-NCA, and O-benzyllevodopa-NCA are as follows: [ka]

[0014] In some embodiments, the alkylene oxide monomers include one or more of ethylene oxide, 1,2-propylene oxide, butylene oxide, 1,2-epoxy-3-methoxypropane, epichlorohydrin, cyclohexene oxide, 1,2-epoxy-4-vinylcyclohexane.

[0015] In some embodiments, catalyst ML comprises one or more of lutetium(III) trifluoromethanesulfonate, iron(III) trifluoromethanesulfonate, zinc(II) trifluoromethanesulfonate, scandium(III) trifluoromethanesulfonate, nickel(II) trifluoromethanesulfonate, copper(II) trifluoromethanesulfonate, iron(III) p-toluenesulfonate, yttrium(III) chloride, zinc p-toluenesulfonate, zinc trifluoroacetate, lutetium p-toluenesulfonate, zinc chloride.

[0016] In some embodiments, the catalyst ML comprises one or more of lutetium(III) trifluoromethanesulfonate, iron(III) trifluoromethanesulfonate, zinc(II) trifluoromethanesulfonate, scandium(III) trifluoromethanesulfonate, nickel(II) trifluoromethanesulfonate, copper(II) trifluoromethanesulfonate, and when L is a trifluoroacetate, the reaction exhibits higher alkylene oxide conversion.

[0017] In some embodiments, the molar ratio of the α-amino acid-N-carboxylic acid anhydride monomer to the alkylene oxide monomer is 1:0.01 to 1:100. The alkylene oxide monomer has relatively low activity and is preferably used in larger amounts. In some embodiments, the molar ratio of the α-amino acid-N-carboxylic acid anhydride monomer to the alkylene oxide monomer is 1:1.5 to 1:50. In some embodiments, the molar ratio of catalyst to monomer, calculated in terms of the total molar amount of monomer, is 1:20 to 1:1000.

[0018] In some embodiments, the solution polymerization is carried out at a temperature of 10 to 100° C. for 1 to 72 hours.

[0019] In some embodiments, the solvent used in the solution polymerization includes one or more of acetonitrile, methyltetrahydrofuran, dioxane, N,N-dimethylformamide, N,N-dimethylacetamide, tetramethylurea, dimethyl sulfoxide, sulfolane, nitrobenzene, benzonitrile, N-methylpyrrolidone, toluene, dichloromethane, chloroform.

[0020] The present invention also provides the use of polypeptide ester ether amine random polymers in the preparation of water-soluble, degradable medical materials, for example, as emulsifiers, surfactants, and solubilizers for lipid-soluble drugs. These random copolymers have excellent solubility, biodegradability, ease of functionalization, processability, and biocompatibility, and can be processed into nanoparticles and hydrogels, making them promising candidates for future applications in the biomedical field. In particular, poly(sarcosine-r-1,2-epoxy-3-methoxypropane) possesses both high water solubility and biodegradability, making it a promising high-quality alternative to polyethylene glycol for medical use. [Effects of the Invention]

[0021] The present invention has the following advantageous effects compared to the prior art.

[0022] (1) This invention is the first to achieve random copolymerization of amino acid monomers and alkylene oxides, synthesizing polypeptide ester ether amine polymers through one-step polymerization of mixed monomers. The random copolymerization products have controllable molecular weights, narrow molecular weight distributions, and tunable copolymer compositions. More importantly, these random copolymerization products are highly soluble, biodegradable, easily functionalized, processable, and biocompatible. They can also be processed into nanoparticles and hydrogels, highlighting their potential for future applications in the biomedical field.

[0023] (2) The method for preparing polypeptide ester ether amine polymers of the present invention has a wide range of raw material sources, is simple to operate, and is highly versatile, and can be applied to most amino acids and alkylene oxides, where amino acids are derived from biomass and alkylene oxides are products of the petroleum industry, both of which are inexpensive, readily available, and available in a wide variety, making them suitable for large-scale industrial production. [Brief explanation of the drawings]

[0024] [Figure 1]1 is an NMR spectrum of the random copolymer poly(sarcosine-r-cyclohexene oxide) prepared in Example 1. [Figure 2] NMR spectrum of the random copolymer poly(sarcosine-r-1,2-epoxy-3-methoxypropane) prepared in Example 2. [Figure 3] 1 is a gel permeation chromatography curve of the enzymatic degradation experiment of the random copolymer prepared in Example 2. [Figure 4] FIG. 11 is a dynamic light scattering diagram of an aqueous solution of the random copolymer prepared in Example 11. DETAILED DESCRIPTION OF THE INVENTION

[0025] In order to make the objectives, technical solutions and advantages of the present invention clearer, the present invention will be described in more detail below based on examples. It should be understood that the specific examples described herein are for illustrating the present invention and do not limit the present invention. After those skilled in the art understand the technical solutions of the present invention, any modifications or equivalent substitutions made without departing from the spirit and scope of the technical solutions of the present invention should all be included in the protection scope of the present invention.

[0026] In the following specific embodiments, the molecular weight and molecular weight distribution of the polymers were measured by gel permeation chromatography (SEC, Waters 1515) (3 mg / L potassium trifluoroacetate in hexafluoroisopropanol, 40° C., flow rate 0.8 mL / min), and nuclear magnetic resonance hydrogen spectroscopy ( 1 H NMR) is measured on a Bruker Avance DMX 400 instrument using deuterated chloroform or deuterated dimethyl sulfoxide as solvent and tetramethylsilane as internal standard. Unless otherwise specified, all raw materials are commercially purchased.

[0027] The hydrodynamic diameter of the polymer nanomicelles in solution was measured using a Zetasizer Nano Series (Malvern Instruments) detector at a wavelength of 657 nm and a fixed angle of 90°. Each sample was measured in triplicate. Example 1

[0028] 1.4 mL of acetonitrile was dissolved in 200 mg of sarcosine-NCA (1.74 mmol) and 10.8 mg of lutetium(III) trifluoromethanesulfonate (0.0174 mmol). Finally, 341 mg of cyclohexene oxide (3.48 mmol) was added. The molar ratio of sarcosine-NCA, cyclohexene oxide, and catalyst was 100:200:1. After shaking well, the mixture was placed in a 60°C oil bath and reacted for 2 days. The polymerization solution was precipitated in ethyl ether, filtered, and vacuum dried to a constant weight to obtain a polypeptide ester ether amine copolymer. The results showed that the SEC number average molecular weight of the polymerization product was 11.5 kg / mol, the molar content of cyclohexene oxide was 0.27, the molar content of sarcosine residues was 0.73, the conversion of sarcosine-NCA monomer was 99%, and the molecular weight distribution was 1.64. 1 The H NMR spectrum (CDCl3) is shown in Figure 1. The signal assignments were clear and the structure was clearly characterized. The obtained product was found to be a polypeptide ester ether amine polymer in which sarcosine and cyclohexene oxide were copolymerized. Example 2

[0029] The same preparation process as in Example 1 was used, except that cyclohexene oxide was replaced with an equal molar amount of 1,2-epoxy-3-methoxypropane, sarcosine-NCA and 1,2-epoxy-3-methoxypropane were copolymerized, and the molar ratio of sarcosine-NCA, 1,2-epoxy-3-methoxypropane, and catalyst was 100:200:1. The test results showed that the polymer product prepared in this example had an SEC number average molecular weight of 9.6 kg / mol, a molar content of 1,2-epoxy-3-methoxypropane of 0.14, a molar content of sarcosine residues of 0.86, a molecular weight distribution of 1.33, and a conversion rate of amino acid monomers of 99%. 1 The H NMR spectrum (DMSO-d6) is shown in Figure 2. The signal assignments were clear, and the structure was clearly characterized. The resulting product was found to be a polypeptide ester ether amine product of sarcosine-NCA and 1,2-epoxy-3-methoxypropane. Testing showed that the copolymer had excellent water solubility (>800 g / L) and was degradable by lipase, making it a promising alternative to polyethylene glycol for medical use. 30 mg of the copolymer prepared in this example and 15 mg of porcine pancreatic lipase were dissolved in 2.7 mL of PBS solution (0.1 mol / L, pH 7.5), and 0.3 mL of ethanol was added. The mixture was incubated at a constant temperature of 37°C for 15 days. Degradation continued until the number-average molecular weight decreased from 9.6 kg / mol to 3.2 kg / mol. The gel permeation chromatography curve of the enzymatic degradation experiment is shown in Figure 3. In conventional techniques, polyamino acids and polyethers themselves are not susceptible to degradation by lipase. The copolymer prepared in this invention has high water solubility and lipase degradability, making it suitable as a substitute for polyethylene glycol to prepare medical auxiliary materials with excellent water solubility and biodegradability. Example 3

[0030] The preparation process was the same as in Example 1, except that sarcosine-NCA was changed to γ-benzyl glutamate-NCA, γ-benzyl glutamate-NCA and cyclohexene oxide were copolymerized, and the molar ratio of γ-benzyl glutamate-NCA, cyclohexene oxide, and catalyst was 30:60:1. As a result of the test, the polymerization product prepared in this example had an SEC number average molecular weight of 1.5 kg / mol, a cyclohexene oxide molar content of 0.49, a γ-benzyl glutamate residue molar content of 0.51, a molecular weight distribution (MwD) of 1.32, and an amino acid monomer conversion of 99%. Example 4

[0031] The preparation process was the same as in Example 1, except that cyclohexene oxide was changed to propylene oxide, sarcosine-NCA and propylene oxide were copolymerized, and the ratio of sarcosine-NCA, propylene oxide, and catalyst was 100:200:1. As a result of the test, the polymerization product prepared in this example had an SEC number average molecular weight of 4.4 kg / mol, a propylene oxide molar content of 0.11, a sarcosine residue molar content of 0.89, a molecular weight distribution of 1.09, and an amino acid monomer conversion of 99%. Example 5

[0032] The preparation process was the same as in Example 1, except that sarcosine-NCA was changed to ε-benzyloxycarbonyllysine-NCA, ε-benzyloxycarbonyllysine-NCA was copolymerized with cyclohexene oxide, and the molar ratio of ε-benzyloxycarbonyllysine-NCA, cyclohexene oxide, and catalyst was 100:200:1. As a result of the test, the polymerization product prepared in this example had an SEC number average molecular weight of 1.6 kg / mol, a cyclohexene oxide molar content of 0.15, a ε-benzyloxycarbonyl lysine residue molar content of 0.85, a molecular weight distribution (Mw) of 1.48, and an amino acid monomer conversion of 99%. Example 6

[0033] The preparation process was the same as in Example 1, except that N-benzylglycine-NCA and cyclohexene oxide were copolymerized, and the molar ratio of N-benzylglycine-NCA, cyclohexene oxide, and catalyst was 30:90:1. As a result of the test, the polymerization product prepared in this example had an SEC number average molecular weight of 1.5 kg / mol, a cyclohexene oxide molar content of 56%, an N-benzylglycine residue molar content of 44%, a molecular weight distribution of 1.20, and an amino acid monomer conversion of 99%. Example 7

[0034] The same preparation process as in Example 1 was used, except that the same molar amount of zinc trifluoroacetate was used as a catalyst instead of lutetium(III) trifluoromethanesulfonate, the solution polymerization temperature was set to 80°C, and the reaction was carried out for 2 days to obtain a random copolymer. As a result of the test, the SEC number average molecular weight of the polymerization product prepared in this example was 9.0 kg / mol, the cyclohexene oxide molar content was 0.07, the sarcosine residue molar content was 0.93, the molecular weight distribution was 1.16, and the amino acid monomer conversion rate was 99%. Example 8

[0035] The same preparation process as in Example 1 was used, except that the same molar amount of iron(III) p-toluenesulfonate was used as the catalyst instead of lutetium(III) trifluoromethanesulfonate, the solution polymerization temperature was set to 80°C, and the reaction was carried out for 2 days to obtain a random copolymer. As a result of the test, the SEC number average molecular weight of the polymerization product prepared in this example was 16.6 kg / mol, the cyclohexene oxide molar content was 0.10, the sarcosine residue molar content was 0.90, the molecular weight distribution was 1.55, and the amino acid monomer conversion was 99%. Example 9

[0036] The same preparation process as in Example 1 was used, except that the same molar amount of scandium(III) trifluoromethanesulfonate was used as the catalyst instead of lutetium(III) trifluoromethanesulfonate, the solution polymerization temperature was set to 80°C, and the reaction was carried out for 2 days to obtain a random copolymer. As a result of the test, the polymerization product prepared in this example had an SEC number average molecular weight of 11.1 kg / mol, a cyclohexene oxide molar content of 0.12, a sarcosine residue molar content of 0.88, a molecular weight distribution of 1.88, and an amino acid monomer conversion of 99%. Example 10

[0037] The same preparation process as in Example 1 was used, except that the same molar amount of iron(III) trifluoromethanesulfonate was used as a catalyst instead of lutetium(III) trifluoromethanesulfonate, the solution polymerization temperature was set to 80°C, and the reaction was carried out for 2 days to obtain a random copolymer. As a result of the test, the SEC number average molecular weight of the polymerization product prepared in this example was 19.8 kg / mol, the cyclohexene oxide molar content was 0.13, the sarcosine residue molar content was 0.87, the molecular weight distribution was 1.53, and the amino acid monomer conversion was 99%. Example 11

[0038] The preparation process was the same as in Example 1, except that the molar ratio of sarcosine-NCA, cyclohexene oxide, and catalyst was 100:400:1. The test results showed that the SEC number average molecular weight of the polymerization product was 8.9 kg / mol, the molar content of cyclohexene oxide was 0.34, the molar content of sarcosine residues was 0.66, the conversion of sarcosine-NCA monomer was 99%, and the molecular weight distribution was 1.77.

[0039] As shown in Figure 4, this polymerization product (hydrophilic-lipophilic balance (HLB) = 11.7) can form nanoparticles with a particle diameter of approximately 400 nm in water, making it useful as a solubilizer for lipid-soluble drugs. The above examples are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above examples. Any other changes, modifications, substitutions, combinations, and simplifications made without departing from the spirit and principles of the present invention are equivalent replacement forms, and all shall fall within the protection scope of the present invention.

Claims

1. A polypeptide ester ether amine random polymer having the following general structural formula: 【Chemistry 1】 (In the formula, R １ , R ２ are independently any one selected from hydrogen, a C1 to C12 saturated aliphatic hydrocarbon group, a C1 to C12 unsaturated aliphatic hydrocarbon group, an aromatic hydrocarbon group, an alkyl ether group, a hydroxyalkyl group, a C1 to C6 hydroxyalkyl group with a protected hydroxy group, a hydroxybenzyl group with a protected hydroxy group, an alkylsulfide group, an alkylindolyl group, a C1 to C6 carboxyalkyl group with a protected carboxy group, and a C1 to C6 aminealkyl group with a protected amine group; or R １ , R ２ are jointly a tetrahydropyrrole, and the substituent is one of a hydroxytetrahydropyrrole in which the hydroxy is protected, R ３ , R ４ are independently any one selected from hydrogen, a C1 to C9 saturated aliphatic hydrocarbon group, and a C1 to C9 unsaturated aliphatic hydrocarbon group, or R ３ , R ４ together constitute one of cyclohexane, methyl-, ethyl-, or vinyl-substituted cyclohexane, x is selected from 0.30 to 0.99, and n is selected from 10 to 500.

2. 2. The polypeptide ester ether amine random polymer according to claim 1, wherein the polypeptide ester ether amine random polymer has a number average molecular weight of 1 to 100 kg / mol and a molecular weight distribution of 2.0 or less.

3. using ML as a catalyst, solution polymerization of a raw material containing an α-amino acid-N-carboxylic acid anhydride monomer and an alkylene oxide monomer to obtain the polypeptide ester ether amine random polymer; 3. The method for preparing a polypeptide ester ether amine random polymer according to claim 1, wherein M in the catalyst ML is a transition metal or a rare earth metal element, and L is one or more of trifluoromethanesulfonate, p-toluenesulfonate, chlorine, bromine, iodine, trifluoroacetate, and acetate.

4. The method for preparing a polypeptide ester ether amine random polymer according to claim 3, characterized in that the structure of the α-amino acid-N-carboxylic acid anhydride monomer is represented by formula (I-1), and the structural formula of the alkylene oxide monomer is represented by formula (I-2). 【Chemistry 2】 (where R １ , R ２ are independently any one selected from hydrogen, a C1 to C12 saturated aliphatic hydrocarbon group, a C1 to C12 unsaturated aliphatic hydrocarbon group, an aromatic hydrocarbon group, an alkyl ether group, a hydroxyalkyl group, a C1 to C6 hydroxyalkyl group with a protected hydroxy group, a hydroxybenzyl group with a protected hydroxy group, an alkylsulfide group, an alkylindolyl group, a C1 to C6 carboxyalkyl group with a protected carboxy group, and a C1 to C6 aminealkyl group with a protected amine group; or R １ , R ２ are jointly tetrahydropyrrole, and the substituent is one of hydroxytetrahydropyrrole in which the hydroxy group is protected, R ３ , R ４ are independently any one selected from hydrogen, a C1 to C9 saturated aliphatic hydrocarbon group, and a C1 to C9 unsaturated aliphatic hydrocarbon group, or R ３ , R ４ together constitute one of cyclohexane, methyl-, ethyl-, or vinyl-substituted cyclohexane.

5. the α-amino acid-N-carboxylic acid anhydride monomers comprise one or more of sarcosine-NCA, N-substituted glycine-NCA, ε-benzyloxycarbonyl lysine-NCA, ε-trifluoroacetyl lysine-NCA, γ-methyl glutamate-NCA, γ-ethyl glutamate-NCA, γ-benzyl glutamate-NCA, β-benzyl aspartate-NCA, phenylalanine-NCA, valine-NCA, leucine-NCA, isoleucine-NCA, methionine-NCA, tert-butyl serine-NCA, alanine-NCA, glycine-NCA, tryptophan-NCA, proline-NCA, threonine-NCA, O-acetyl hydroxyproline-NCA, O-benzyl tyrosine-NCA, O-benzyl levodopa-NCA; The method for preparing a polypeptide ester ether amine random polymer according to claim 3, characterized in that the structure of the N-substituted glycine-NCA is represented by formula (I-3). 【Transformation 3】 (where R ５ is selected from a C2 to C12 saturated aliphatic hydrocarbon group, a C2 to C12 unsaturated aliphatic hydrocarbon group, an aromatic hydrocarbon group, an alkyl ether group, an alkyl sulfide group, a C1 to C6 carboxyalkyl group in which the carboxy group is protected, and a C1 to C6 aminealkyl group in which the amino group is protected; and / or the alkylene oxide monomers include one or more of ethylene oxide, 1,2-propylene oxide, butylene oxide, 1,2-epoxy-3-methoxypropane, epichlorohydrin, cyclohexene oxide, 1,2-epoxy-4-vinylcyclohexane.

6. 4. The method for preparing a polypeptide ester ether amine random polymer according to claim 3, wherein the catalyst ML comprises one or more of lutetium(III) trifluoromethanesulfonate, iron(III) trifluoromethanesulfonate, zinc(II) trifluoromethanesulfonate, scandium(III) trifluoromethanesulfonate, nickel(II) trifluoromethanesulfonate, copper(II) trifluoromethanesulfonate, iron(III) p-toluenesulfonate, yttrium(III) chloride, zinc p-toluenesulfonate, zinc trifluoroacetate, lutetium p-toluenesulfonate, and zinc chloride.

7. The method for preparing polypeptide ester ether amine random polymers according to claim 3, characterized in that the molar ratio of the α-amino acid-N-carboxylic acid anhydride monomer to the alkylene oxide monomer is 1:0.01 to 1:

100.

8. 4. The method for preparing a polypeptide ester ether amine random polymer according to claim 3, wherein the molar ratio of the catalyst to the monomer is 1:20 to 1:1000 in terms of the total molar amount of the monomer.

9. The method for preparing a polypeptide ester ether amine random polymer according to claim 3, characterized in that the solution polymerization is carried out at a temperature of 10 to 100°C for 1 to 72 hours.

10. Use of the polypeptide ester ether amine random polymer according to claim 1 or 2 in the preparation of a water-soluble degradable medical material.

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