Polypeptide ester etheramine random polymer, as well as method for preparing and using the same.

Abstract

This invention provides polypeptide ester etheramine random polymers and methods for preparing them. [Solution] The polypeptide ester etheramine random polymer of the present invention is a random copolymer of an amino acid monomer and an alkylene oxide. In the present invention, copolymerization of an amino acid monomer and an alkylene oxide monomer is achieved by a one-step method of mixed monomers using a transition metal or rare earth metal salt as a catalyst. The random copolymer product has a controllable molecular weight, a narrow molecular weight distribution, and an adjustable copolymer composition. Furthermore, the random copolymer product has excellent solubility, is biodegradable, easily modifiable with functional groups, has excellent processability, and has 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 the preparation of medical polymer materials, and specifically relates to polypeptide ester ether amine random polymers, as well as their preparation methods and uses.

Background Art

[0002] The structural unit of poly-α-amino acid (PAA: poly(amino acid)) is an α-amino acid residue, which is the same as or similar to the α-amino acid repeating unit structure of protein peptide chains in vivo, has excellent biocompatibility, and can be used as a biomedical polymer material. The commonly used method for the synthesis of poly-α-amino acid is the ring-opening polymerization method of α-amino acid-N-carboxylic acid anhydride (NCA) (Chem. Soc. Rev., 2013, 42, 7373-7390). Currently, the random copolymerization of amino acid-based monomers mainly focuses on the copolymerization of different amino acid-based monomers, and there are no reports on the random copolymerization with other non-nitrogen-based monomers. As a result, the main chains of the copolymerization products are all linked by rigid amide bonds (peptide bonds), and the possibility of structural design for specific applications is limited. Even the only report on the polymerization of lactide and γ-benzyl glutamate-NCA mixed monomers shows that the two monomers polymerize independently in sequence to produce a block polymer rather than a random polymer (Macromolecules 2024, 57, 5691-5701).

[0003] Alkylene oxide is a common industrial product, the basic raw material of epoxy resin, and is widely used in binders, paints and composite materials. Alkylene oxide is an excellent copolymerization monomer because it has a rich variety, is inexpensive, and is easy to functionalize and modify. However, currently, there are still no reports on the copolymerization of amino acid-based monomers and alkylene oxide. The main reason is that the activities of the nitrogen-terminal chain growth center generated during the polymerization of amino acid-based monomers and the oxygen-terminal center of non-nitrogen-based monomers are greatly different, making it difficult to achieve random copolymerization. [Overview of the Initiative] [Problems that the invention aims to solve]

[0004] This invention addresses the challenge of difficulty in polymerizing amino acid monomers and non-nitrogen monomers, and proposes for the first time a polypeptide ester etheramine polymer obtained by random copolymerization of amino acid monomers and alkylene oxides. This copolymer has several advantages, including controllable molecular weight, a narrow molecular weight distribution, excellent solubility, biodegradability, ease of functionalization modification, excellent processability, and excellent biocompatibility. [Means for solving the problem]

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

[0006] Polypeptide ester etheramine random polymers have the following general structural formula. [ka] (In the formula, R1 and R2 are independently selected from 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 hydroxy-protected C1-C6 hydroxyalkyl group, a hydroxy-protected hydroxybenzyl group, an alkyl sulfide group, an alkyl indolyl group, a carboxy-protected C1-C6 carboxyalkyl group, or a amine-protected C1-C6 aminealkyl group; or R1 and R2 together are tetrahydropyrrole, and the substituent is any one of hydroxy-protected hydroxytetrahydropyrrole.) R3 and R4 are independently selected from hydrogen, a C1-C9 saturated aliphatic hydrocarbon group, or a C1-C9 unsaturated aliphatic hydrocarbon; or R3 and R4 together constitute one of cyclohexane, a methyl group, an ethyl group, or a vinyl group-substituted cyclohexane, where x is selected from 0.30 to 0.99 and n is selected from 10 to 500.

[0007] In some embodiments, the polypeptide ester etheramine 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 etheramine random polymer has a number-average molecular weight of 1 to 50 kg / mol.

[0008] The random copolymers provided in this invention simultaneously possess amide bonds (peptide bonds), ester bonds, ether bonds, and amine groups in their main chain, improving properties such as water solubility, biodegradability, and biocompatibility. They are also easily functionalized, have controllable molecular weights, a narrow molecular weight distribution, and allow for adjustment of the copolymer composition. Through structural design, copolymers that meet the needs of various applications can be obtained.

[0009] The present invention also involves 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 to obtain the polypeptide ester etheramine random polymer. The present invention provides a method for preparing a polypeptide ester etheramine random polymer, wherein M in 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 enables random copolymerization of α-amino acid-N-carboxylic acid anhydride monomers and alkylene oxides using a transition metal or rare earth metal salt as a catalyst. Here, the transition metal salt cannot directly catalyze the polymerization of the amino acid-N-carboxylic acid anhydride monomer; the copolymerization of the two must proceed smoothly in the presence of the alkylene oxide. This method avoids multi-step reactions by introducing ester, ether, and amine groups into the polyamide, providing a novel and simple synthesis method for functionalizing polyamides. This method is versatile for various α-amino acid-N-carboxylic acid anhydride monomers and alkylene oxides.

[0010] Research has shown that various substituents in α-amino acid-NCA monomers that do not contain active hydrogen, such as alkyl groups, aromatic groups, ethers, thioethers, amide groups, and ester groups, have little effect on the performance of the five-membered ring-opening polymerization reaction in the monomer structure. 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 shown by formula (I-1), and the structural formula of the alkylene oxide monomer is shown by formula (I-2). [ka] (Here, R1 and R2 are independently selected from 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 hydroxy-protected C1-C6 hydroxyalkyl group, a hydroxy-protected hydroxybenzyl group, an alkyl sulfide group, an alkyl indolyl group, a carboxy-protected C1-C6 carboxyalkyl group, or a amine-protected C1-C6 aminealkyl group; or R1 and R2 together are tetrahydropyrrole, and the substituent is any one of hydroxy-protected hydroxytetrahydropyrrole.) R3 and R4 are independently selected from hydrogen, a C1-C9 saturated aliphatic hydrocarbon group, or a C1-C9 unsaturated aliphatic hydrocarbon, or R3 and R4 together constitute one of cyclohexane, a methyl group, an ethyl group, or a vinyl group-substituted cyclohexane.

[0011] In some embodiments, the α-amino acid-N-carboxylic acid anhydride monomer includes one or more of the following: sarcosine-NCA, N-substituted glycine-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, 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 C2-C12 saturated aliphatic hydrocarbon groups, C2-C12 unsaturated aliphatic hydrocarbon groups, aromatic hydrocarbon groups, alkyl ether groups, alkyl sulfide groups, C1-C6 carboxyalkyl groups with protected carboxyl groups, and C1-C6 amine alkyl groups with protected amino groups.)

[0013] The structural formulas for 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 monomer includes one or more of ethylene oxide, 1,2-propylene oxide, butylene oxide, 1,2-epoxy-3-methoxypropane, epichlorohydrin, cyclohexene oxide, and 1,2-epoxy-4-vinylcyclohexane.

[0015] In some embodiments, catalyst ML comprises one or more of the following: 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(III) p-toluenesulfonate, and zinc chloride.

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

[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 it is preferable to use a larger amount. 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, in terms of the total molar amount of the monomers, the molar ratio of the catalyst to the monomers 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 a time of 1 to 72 h.

[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, and chloroform.

[0020] The present invention also provides the use of polypeptide ester etheramine random polymers as, for example, emulsifiers, surfactants, and solubilizers for lipid-soluble drugs in the preparation of water-soluble and biodegradable medical materials. These random copolymers have excellent solubility, are biodegradable, easily functionalized, processable, and biocompatible, and can be processed into nanoparticles and hydrogels, making them promising 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 medical-grade polyethylene glycol. [Effects of the Invention]

[0021] Compared to the prior art, the present invention has the following beneficial effects.

[0022] (1) The present invention is the first to realize random copolymerization of amino acid monomers and alkylene oxides, and synthesizes polypeptide ester etheramine polymers by one-step polymerization of the mixed monomers. The random copolymer product has a controllable molecular weight, a narrow molecular weight distribution, and an adjustable copolymer composition. More importantly, the random copolymer product has excellent solubility, is biodegradable, easily modifiable with functional groups, has excellent processability, and is biocompatible, and can be processed into nanoparticles and hydrogels, and is expected to have future applications in the biomedical field.

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

[0024] [Figure 1]This is the NMR spectrum of poly(sarcosine-r-cyclohexene oxide), a random copolymer prepared in Example 1. [Figure 2] This is the NMR spectrum of (sarcosine-r-1,2-epoxy-3-methoxypropane), a random copolymer poly prepared in Example 2. [Figure 3] This is the gel permeation chromatography curve of the enzymatic degradation experiment of the random copolymer prepared in Example 2. [Figure 4] This is a dynamic light scattering diagram of the aqueous solution of the random copolymer prepared in Example 11. [Modes for carrying out the invention]

[0025] To further clarify the object, technical solution, and advantages of the present invention, 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 illustrative purposes only and do not limit the present invention. Any modifications or equivalent substitutions made by those skilled in the art, without departing from the spirit and scope of the technical solution, should all be within the scope of protection of the present invention.

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

[0027] The hydrodynamic diameter of polymer nanomicelles in solution is detected using a Zetasizer Nano Series (Malvern Instruments) detector at a measurement wavelength of 657 nm and a fixed angle of 90°. Each sample is measured three times in parallel. 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, and the molar ratio of sarcosine-NCA, cyclohexene oxide, and catalyst was 100:200:1. After shaking well, the mixture was reacted in an oil bath at 60°C for 2 days. The polymerization solution was precipitated in ethyl ether, filtered, and vacuum-dried until a constant weight was obtained to obtain polypeptide ester etheramine copolymer. The test 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 rate of sarcosine-NCA monomer was 99%, and the molecular weight distribution was 1.64. 1 The 1H NMR spectrum (CDCl3) is shown in Figure 1. The assignment of each signal was clear, and the structure was clearly characterized, indicating that the obtained product is a polypeptide ester etheramine polymer copolymerized from sarcosine and cyclohexene oxide. Example 2

[0029] The preparation process was the same as in Example 1, except that cyclohexene oxide was replaced with an equal molar amount of 1,2-epoxy-3-methoxypropane to copolymerize sarcosine-NCA and 1,2-epoxy-3-methoxypropane, and the molar ratio of sarcosine-NCA, 1,2-epoxy-3-methoxypropane to the 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 an amino acid monomer conversion rate of 99%. 1 The 1H NMR spectrum (DMSO-d6) is shown in Figure 2. The assignment of each signal was clear, the structure was clearly characterized, and the obtained product was found to be a polypeptide ester etheramine product of sarcosine-NCA and 1,2-epoxy-3-methoxypropane. The test results showed that this copolymer has excellent water solubility (>800 g / L) and is lipase-degradable, making it a promising alternative to medical-grade polyethylene glycol. In this example, 30 mg of the copolymer prepared 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 easily degraded by lipase. The copolymer prepared in this invention has high water solubility and lipase degradation properties, and can be used as a substitute for polyethylene glycol to prepare medical auxiliary materials with superior water solubility and biodegradability. Example 3

[0030] The preparation process was the same as in Example 1, except that sarcosine-NCA was replaced with γ-benzyl glutamate-NCA, γ-benzyl glutamate-NCA was copolymerized with cyclohexene oxide, and the molar ratio of γ-benzyl glutamate-NCA, cyclohexene oxide, and catalyst was 30:60:1. The test results showed that 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 of 1.32, and an amino acid monomer conversion rate of 99%. Example 4

[0031] The preparation process was the same as in Example 1, except that cyclohexene oxide was replaced with propylene oxide to copolymerize sarcosine-NCA and propylene oxide, and the ratio of sarcosine-NCA, propylene oxide, and catalyst was 100:200:1. The test results showed that 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 rate of 99%. Example 5

[0032] The preparation process was the same as in Example 1, except that sarcosine-NCA was replaced with 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. The test results showed that 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, an ε-benzyloxycarbonyllysine residue molar content of 0.85, a molecular weight distribution of 1.48, and an amino acid monomer conversion rate 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. The test results showed that 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%, a N-benzylglycine residue molar content of 44%, a molecular weight distribution of 1.20, and an amino acid monomer conversion rate of 99%. Example 7

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

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

[0036] The preparation process was the same as in Example 1, except that scandium(III) trifluoromethanesulfonate was used as a catalyst in the same molar amount as lutetium(III) trifluoromethanesulfonate, and the solution polymerization temperature was set to 80°C and the reaction was carried out for 2 days to obtain a random copolymer. The test results showed that 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 rate of 99%. Example 10

[0037] The preparation process was the same as in Example 1, except that iron(III) trifluoromethanesulfonate was used as a catalyst in the same molar amount as lutetium(III) trifluoromethanesulfonate, and the solution polymerization temperature was set to 80°C and the reaction was carried out for 2 days to obtain a random copolymer. The test results showed that the polymerization product prepared in this example had an SEC number-average molecular weight of 19.8 kg / mol, a cyclohexene oxide molar content of 0.13, a sarcosine residue molar content of 0.87, a molecular weight distribution of 1.53, and an amino acid monomer conversion rate of 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 cyclohexene oxide molar content was 0.34, the sarcosine residue molar content was 0.66, the sarcosine-NCA monomer conversion rate was 99%, and the molecular weight distribution was 1.77.

[0039] As shown in Figure 4, this polymerization product (hydrophilic-lipophilic balance value (HLB) = 11.7) can form nanoparticles with a particle size of approximately 400 nm in water and is useful as a solubilizer for lipid-soluble drugs. While the above embodiments are preferred embodiments of the present invention, the embodiments of the present invention are not limited to those above, and any other modifications, alterations, substitutions, combinations, or simplifications made without departing from the spirit and principles of the present invention are equivalent substitutions and are all within the scope of protection of the present invention.

Claims

1. A polypeptide ester etheramine random polymer characterized by having the following general structural formula. 【Chemistry 1】 (In the formula, R １ , R ２ R is independently one selected from 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 hydroxy-protected C1-C6 hydroxyalkyl group, a hydroxy-protected hydroxybenzyl group, an alkyl sulfide group, an alkyl indolyl group, a carboxy-protected C1-C6 carboxyalkyl group, or a amine-protected C1-C6 aminealkyl group, or R １ , R ２ The compound is tetrahydropyrrole, and the substituent is one of the hydroxy-protected hydroxytetrahydropyrrole compounds. R ３ , R ４ R is independently one of the following: hydrogen, a C1-C9 saturated aliphatic hydrocarbon group, or a C1-C9 unsaturated aliphatic hydrocarbon, or R ３ , R ４ (These two groups together constitute one of cyclohexane, a methyl group, an ethyl group, or a vinyl group-substituted cyclohexane, where x is selected from 0.30 to 0.99 and n is selected from 10 to 500.)

2. The polypeptide ester etheramine random polymer according to claim 1, characterized in that the polypeptide ester etheramine 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, a raw material containing an α-amino acid-N-carboxylic acid anhydride monomer and an alkylene oxide monomer is solution polymerized to obtain the polypeptide ester etheramine random polymer. A method for preparing a polypeptide ester etheramine random polymer according to claim 1 or 2, characterized in that M in 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.

4. The method for preparing a polypeptide ester etheramine random polymer according to claim 3, characterized in that the structure of the α-amino acid-N-carboxylic acid anhydride monomer is shown by formula (I-1), and the structural formula of the alkylene oxide monomer is shown by formula (I-2). 【Chemistry 2】 (Here, R １ , R ２ is independently any one selected from 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 in which the hydroxy group is protected, a hydroxybenzyl group in which the hydroxy group is protected, an alkyl sulfide group, an alkyl indolyl group, a C1-C6 carboxyalkyl group in which the carboxy group is protected, a C1-C6 amine alkyl group in which the amine group is protected, or R １ , R ２ are jointly any one of tetrahydropyrrole and hydroxytetrahydropyrrole in which the hydroxy group is protected, R ３ , R ４ R is independently one of the following: hydrogen, a C1-C9 saturated aliphatic hydrocarbon group, or a C1-C9 unsaturated aliphatic hydrocarbon, or R ３ , R ４ (These two compounds together constitute one of the following: cyclohexane, methyl group, ethyl group, or vinyl group-substituted cyclohexane.)

5. The α-amino acid-N-carboxylic acid anhydride monomer includes one or more of the following: sarcosine-NCA, N-substituted glycine-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-benzyllevodoper-NCA. The method for preparing a polypeptide ester etheramine 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】 (Here, R ５ These are selected from C2-C12 saturated aliphatic hydrocarbon groups, C2-C12 unsaturated aliphatic hydrocarbon groups, aromatic hydrocarbon groups, alkyl ether groups, alkyl sulfide groups, C1-C6 carboxyalkyl groups with protected carboxyl groups, and C1-C6 aminealkyl groups with protected amino groups. (and / or, the alkylene oxide monomer includes one or more of ethylene oxide, 1,2-propylene oxide, butylene oxide, 1,2-epoxy-3-methoxypropane, epichlorohydrin, cyclohexene oxide, and 1,2-epoxy-4-vinylcyclohexane.)

6. The method for preparing a polypeptide ester etheramine random polymer according to claim 3, characterized in that the catalyst ML contains one or more of the following: 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(III) p-toluenesulfonate, and zinc chloride.

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

10. Use of the polypeptide ester etheramine random polymer according to claim 1 or 2 in the preparation of water-soluble biodegradable medical materials.

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