A kind of polypeptide ester ether amine random polymer and its preparation method and application

Abstract

The present invention discloses a random polymer of polypeptide ester ether amine and a preparation method and application thereof. The random polymer of polypeptide ester ether amine is a random copolymer of amino acid monomers and alkylene oxide. In the present invention, a transition metal or rare earth metal salt is used as a catalyst, and a mixed monomer one-step method is used to realize the copolymerization of amino acid monomers and alkylene oxide monomers. The molecular weight of the random copolymer product is controllable, the molecular weight distribution is narrow, and the copolymer composition is adjustable. The random copolymer product has good solubility, biodegradability, easy functionalization modification, good processing performance, and good biocompatibility, and has broad application prospects in the biomedical field.

Description

Technical Field

[0001] The invention relates to the technical field of preparation of medical polymer materials, and in particular to a polypeptide ester ether amine random polymer and a preparation method and application thereof. Background Art

[0002] The structural unit of poly-α-amino acid (PAA) is α-amino acid residue, which is the same or similar to the α-amino acid repeating unit structure of protein peptide chains in organisms. It has excellent biocompatibility and can be used as biomedical polymer materials. The commonly used method for synthesizing poly-α-amino acid is the α-amino acid-N-carboxylic anhydride (NCA) ring-opening polymerization method (Chem. Soc. Rev., 2013, 42, 7373-7390). At present, the random copolymerization of amino acid monomers mainly focuses on the copolymerization of different amino acid monomers, and there are no reports on random copolymerization with other non-nitrogen monomers. This results in the main chain of the copolymer product being rigidly connected by amide bonds (peptide bonds), which limits its structural design capabilities for specific applications. The only report on the polymerization of lactide and γ-benzyl glutamate-NCA mixed monomers is that the two monomers are polymerized independently in sequence to generate block polymers rather than random polymers (Macromolecules 2024, 57, 5691-5701).

[0003] Alkylene oxide is a common industrial product and the basic raw material of epoxy resin. It is widely used in adhesives, coatings and composite materials. Alkylene oxide is rich in variety, low in price, easy to functionalize and modify, and is an excellent copolymer monomer. However, there are no reports on the copolymerization of amino acid monomers and alkylene oxides. The main reason is that the activity of the nitrogen terminal chain growth center generated during the polymerization of amino acid monomers is quite different from that of the oxygen terminal center of non-nitrogen monomers, making it difficult to achieve random copolymerization. Summary of the invention

[0004] The present invention aims at the problem of difficulty in polymerizing amino acid monomers and non-nitrogen monomers, and for the first time proposes a polypeptide ester ether amine polymer of random copolymerization of amino acid monomers and alkylene oxide. The copolymer has controllable molecular weight, narrow molecular weight distribution, good solubility, biodegradability, easy functionalization modification, good processing performance, good biocompatibility and the like.

[0005] To achieve the above object, the technical solution adopted by the present invention is:

[0006] A polypeptide ester ether amine random polymer has the following general structural formula:

[0007] ;

[0008] In the formula, R1 and R2 are independently selected from any one of hydrogen, C1-C12 saturated aliphatic hydrocarbon group, C1-C12 unsaturated aliphatic hydrocarbon group, aromatic hydrocarbon group, alkyl ether group, hydroxyalkyl group, C1-C6 hydroxyalkyl group with protected hydroxyl group, hydroxybenzyl group with protected hydroxyl group, alkyl thioether group, alkyl indolyl group, C1-C6 carboxyalkyl group with protected carboxyl group, and C1-C6 aminoalkyl group with protected amine group; or R1 and R2 together form tetrahydropyrrole, and the substituent is any one of hydroxytetrahydropyrrole with protected hydroxyl group;

[0009] R3 and R4 are independently selected from any one of hydrogen, C1-C9 saturated aliphatic hydrocarbon group and C1-C9 unsaturated aliphatic hydrocarbon; or R3 and R4 together constitute cyclohexane, methyl, ethyl or vinyl substituted cyclohexane; x is selected from 0.30-0.99, and n is selected from 10-500.

[0010] In some embodiments, the number average molecular weight of the polypeptide ester ether amine random polymer is 1-100 kg / mol, and the molecular weight distribution is below 2.0. In some embodiments, the number average molecular weight of the polypeptide ester ether amine random polymer is 1-50 kg / mol.

[0011] The random copolymer provided in the present invention has amide bonds (peptide bonds), ester bonds, ether bonds and amine groups on the main chain, which can improve the water solubility, biodegradability and biocompatibility of the copolymer. The structure is easy to functionalize and modify, the molecular weight is controllable, the molecular weight distribution is narrow, and the copolymer composition is adjustable. Through structural design, copolymers that meet the needs of various scenarios can be obtained.

[0012] The present invention also provides a method for preparing the polypeptide ester ether amine random polymer, wherein ML is used as a catalyst to subject a raw material comprising an α-amino acid-N-carboxylic anhydride monomer and an alkylene oxide monomer to solution polymerization to obtain the polypeptide ester ether amine random polymer;

[0013] In the catalyst ML, M 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.

[0014] The present invention uses transition metal or rare earth metal salt as a catalyst to achieve random copolymerization of α-amino acid-N-carboxylic anhydride monomer and alkylene oxide. Among them, transition metal salt cannot directly catalyze the polymerization of amino acid-N-carboxylic anhydride monomer, and the copolymerization of the two must be carried out smoothly in the presence of alkylene oxide. This method introduces ester bonds, ether bonds and amine groups into polyamide, avoids multi-step reactions, and provides a novel and convenient synthesis method for the functionalization of polyamide. This method is universal to various α-amino acid-N-carboxylic anhydride monomers and alkylene oxides.

[0015] Studies have found that the alkyl, aromatic, ether, thioether, amide, ester and other substituents without active hydrogen on the α-amino acid-NCA monomer have little effect on the five-membered ring opening polymerization performance in the monomer structure. Therefore, the α-amino acid-NCA monomers with the above-mentioned different substituents are suitable for the polymerization reaction system of the present invention. In some embodiments, the structure of the α-amino acid-N-carboxylic anhydride monomer is shown in formula (I-1), and the structure of the alkylene oxide monomer is shown in formula (I-2);

[0016] (I-1), (I-2);

[0017] Wherein R1 and R2 are independently selected from any one of hydrogen, C1-C12 saturated aliphatic hydrocarbon group, C1-C12 unsaturated aliphatic hydrocarbon group, aromatic hydrocarbon group, alkyl ether group, hydroxyalkyl group, C1-C6 hydroxyalkyl group with protected hydroxyl group, hydroxybenzyl group with protected hydroxyl group, alkyl thioether group, alkyl indolyl group, C1-C6 carboxyalkyl group with protected carboxyl group, and C1-C6 aminoalkyl group with protected amine group; or R1 and R2 together form tetrahydropyrrole, and the substituent is any one of hydroxytetrahydropyrrole with protected hydroxyl group;

[0018] R3 and R4 are independently selected from any one of hydrogen, C1-C9 saturated aliphatic hydrocarbon group and C1-C9 unsaturated aliphatic hydrocarbon; or R3 and R4 together constitute cyclohexane, methyl, ethyl or vinyl substituted cyclohexane.

[0019] In some embodiments, the α-amino acid-N-carboxylic acid anhydride monomer includes 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-acetyl hydroxyproline-NCA, O-benzyl tyrosine-NCA, O-benzyldopa amino acid-NCA, and the like.

[0020] In some embodiments, the N-substituted glycine-NCA structure is shown in formula (I-3):

[0021] (I-3) ;

[0022] Wherein R5 is selected from C2~C12 saturated aliphatic hydrocarbon group, C2~C12 unsaturated aliphatic hydrocarbon group, aromatic hydrocarbon group, alkyl ether group, alkyl thioether group, C1~C6 carboxyalkyl group with protected carboxyl group, and C1~C6 aminealkyl group with protected amino group.

[0023] 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-benzyldopa-NCA are as follows:

[0024]

[0025]

[0026]

[0027]

[0028]

[0029] 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.

[0030] 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, copper (II) trifluoromethanesulfonate, iron (III) p-toluenesulfonate, yttrium (III) chloride, zinc p-toluenesulfonate, zinc trifluoroacetate, lutetium p-toluenesulfonate, and zinc chloride.

[0031] In some embodiments, the catalyst ML is 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 shows a higher alkylene oxide conversion rate.

[0032] 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 activity of the alkylene oxide monomer is relatively low, and a larger amount is preferably used. 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.

[0033] In some embodiments, the molar ratio of the catalyst to the monomer is 1:20 to 1:1000 based on the total molar amount of the monomer.

[0034] In some embodiments, the solution polymerization is carried out at a temperature of 10 to 100° C. and for a time of 1 to 72 hours.

[0035] 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.

[0036] The present invention also provides the use of the polypeptide ester ether amine random polymer in the preparation of water-soluble and degradable medical materials, such as emulsifiers, surfactants and solubilizers for fat-soluble drugs. The random copolymer product has good solubility, biodegradability, easy functionalization modification, good processing performance, and good biocompatibility. It can be prepared into nanoparticles and hydrogels, and has broad application prospects in the biomedical field. In particular, poly (sarcosine-r-1,2-epoxy-3-methoxypropane) has both high water solubility and biodegradability, and is a potential high-quality substitute for medical polyethylene glycol.

[0037] Compared with the prior art, the present invention has the following beneficial effects:

[0038] (1) The present invention realizes the random copolymerization of amino acid monomers and alkylene oxides for the first time, and synthesizes polypeptide ester ether amine polymers by one-step polymerization of mixed monomers. The molecular weight of the random copolymer product is controllable, the molecular weight distribution is narrow, and the copolymer composition is adjustable. More importantly, the random copolymer product has good solubility, biodegradability, easy functionalization modification, good processing performance, and good biocompatibility. It can be prepared into nanoparticles and hydrogels, and has broad application prospects in the biomedical field.

[0039] (2) The preparation method of the polypeptide ester ether amine polymer of the present invention has a wide range of raw material sources, is simple to operate, and has strong universality. It is applicable to most amino acids and alkylene oxides. Amino acids have biomass sources, and alkylene oxides are petroleum industry products. Both are cheap, easy to obtain, and rich in variety, and are suitable for large-scale industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] Figure 1This is the NMR spectrum of the random copolymer poly(sarcosine-r-cyclohexene oxide) prepared in Example 1.

[0041] Figure 2 This is the NMR spectrum of the random copolymer poly(sarcosine-r-1,2-epoxy-3-methoxypropane) prepared in Example 2.

[0042] Figure 3 This is a gel permeation chromatography curve of the random copolymer enzyme degradation experiment prepared in Example 2.

[0043] Figure 4 This is the dynamic light scattering diagram of the random copolymer aqueous solution prepared in Example 11. DETAILED DESCRIPTION

[0044] In order to make the purpose, technical scheme and advantages of the present invention clearer, the present invention is further described in detail below in conjunction with embodiment. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention. Those skilled in the art can make modifications or equivalent substitutions based on the understanding of the technical scheme of the present invention without departing from the spirit and scope of the technical scheme of the present invention, and all should be included in the protection scope of the present invention.

[0045] In the following specific embodiments, the molecular weight and molecular weight distribution of the polymer were determined by gel permeation chromatography (SEC, Waters 1515) (hexafluoroisopropanol containing 3 mg / L potassium trifluoroacetate, 40°C, flow rate 0.8 mL / min); H NMR ( 1 H NMR) was measured on a Bruker Avance DMX 400 instrument, using deuterated chloroform or deuterated dimethyl sulfoxide as solvent and tetramethylsilane as internal standard. Raw materials were purchased from the market unless otherwise specified.

[0046] The hydrodynamic diameter of the polymer nanomicelles in solution was detected by a Zetasizer Nano Series (Malvern Instruments) detector at a wavelength of 657 nm and a fixed angle of 90°. Each sample was tested three times in parallel.

[0047] Example 1

[0048] Dissolve 200 mg of sarcosine-NCA (1.74 mmol) and 10.8 mg of lutetium (III) trifluoromethanesulfonate (0.0174 mmol) in 1.4 mL of acetonitrile, and finally add 341 mg of cyclohexene oxide (3.48 mmol). The molar ratio of sarcosine-NCA, cyclohexene oxide and catalyst is 100:200:1. After shaking, place in a 60 °C oil bath for two days. The polymerization solution is precipitated in ether, filtered, and vacuum dried to constant weight to obtain a polypeptide ester ether amine copolymer.

[0049] After testing, the SEC number average molecular weight of the polymer 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 HNMR spectrum (CDCl3) Figure 1 As shown, the signals are clearly assigned and the structure is clearly characterized, indicating that the obtained product is a polypeptide ester ether amine polymer copolymerized with sarcosine and cyclohexene oxide.

[0050] Example 2

[0051] The preparation process of Example 1 is followed, except that cyclohexene oxide is replaced with an equal molar amount of 1,2-epoxy-3-methoxypropane to copolymerize sarcosine-NCA and 1,2-epoxy-3-methoxypropane. The molar ratio of sarcosine-NCA, 1,2-epoxy-3-methoxypropane and the catalyst is 100:200:1.

[0052] After testing, the SEC number average molecular weight of the polymer product prepared in this example is 9.6 kg / mol, the molar content of 1,2-epoxy-3-methoxypropane is 0.14, the molar content of sarcosine residues is 0.86, the molecular weight distribution is 1.33, and the amino acid monomer conversion rate is 99%. 1 HNMR spectrum (DMSO-d6) Figure 2 As shown, the signals are clearly assigned and the structure is clearly characterized, indicating that the obtained product is the polypeptide ester ether amine product of sarcosine-NCA and 1,2-epoxy-3-methoxypropane.

[0053] The test showed that the copolymer has excellent water solubility (>800g / L) and is biodegradable by lipase, making it a potential good substitute for medical polyethylene glycol.

[0054] 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 cultured at 37 °C for 15 days. The number average molecular weight was degraded from 9.6 kg / mol to 3.2 kg / mol. The gel permeation chromatography curve of the enzyme degradation experiment is shown in FIG. Figure 3 In the prior art, polyamino acids and polyethers themselves are not likely to be degraded by lipase. The copolymer prepared in the present invention has high water solubility and lipase degradability, and can be used as a substitute for polyethylene glycol to prepare medical auxiliary materials with better water solubility and biodegradability.

[0055] Example 3

[0056] The preparation process of Example 1 is followed, except that sarcosine-NCA is replaced by γ-benzyl glutamate-NCA, γ-benzyl glutamate-NCA is copolymerized with cyclohexene oxide, and the molar ratio of γ-benzyl glutamate-NCA, cyclohexene oxide and catalyst is 30:60:1.

[0057] After testing, the SEC number average molecular weight of the polymer product prepared in this example is 1.5 kg / mol, the molar content of cyclohexene oxide is 0.49, the molar content of γ-benzyl glutamate residue is 0.51, the molecular weight distribution is 1.32, and the amino acid monomer conversion rate is 99%.

[0058] Example 4

[0059] The preparation process of Example 1 is the same, except that cyclohexene oxide is used instead of propylene oxide to copolymerize sarcosine-NCA and propylene oxide. The ratio of sarcosine-NCA, propylene oxide and catalyst is 100:200:1.

[0060] After testing, the SEC number average molecular weight of the polymer product prepared in this example is 4.4 kg / mol, the molar content of propylene oxide is 0.11, the molar content of sarcosine residues is 0.89, the molecular weight distribution is 1.09, and the amino acid monomer conversion rate is 99%.

[0061] Example 5

[0062] The preparation process of Example 1 is the same, except that sarcosine-NCA is replaced by ε-benzyloxycarbonyllysine-NCA, and ε-benzyloxycarbonyllysine-NCA is copolymerized with cyclohexene oxide. The molar ratio of ε-benzyloxycarbonyllysine-NCA, cyclohexene oxide and catalyst is 100:200:1.

[0063] After testing, the SEC number average molecular weight of the polymer product prepared in this example is 1.6 kg / mol, the molar content of cyclohexene oxide is 0.15, the molar content of ε-benzyloxycarbonyllysine residue is 0.85, the molecular weight distribution is 1.48, and the amino acid monomer conversion rate is 99%.

[0064] Example 6

[0065] The preparation process of Example 1 is the same, except that N-benzylglycine-NCA and cyclohexene oxide are copolymerized, and the molar ratio of N-benzylglycine-NCA, cyclohexene oxide and catalyst is 30:90:1.

[0066] After testing, the SEC number average molecular weight of the polymer product prepared in this example is 1.5 kg / mol, the molar content of cyclohexene oxide is 56%, the molar content of N-benzylglycine residues is 44%, the molecular weight distribution is 1.20, and the amino acid monomer conversion rate is 99%.

[0067] Example 7

[0068] The preparation process of Example 1 was followed, except that an equal molar amount of zinc trifluoroacetate was used to replace lutetium (III) trifluoromethanesulfonate as the catalyst, the solution polymerization temperature was 80 °C, and the reaction time was two days to obtain a random copolymer.

[0069] After testing, the SEC number average molecular weight of the polymer product prepared in this example was 9.0 kg / mol, the molar content of cyclohexene oxide was 0.07, the molar content of sarcosine residues was 0.93, the molecular weight distribution was 1.16, and the amino acid monomer conversion rate was 99%.

[0070] Example 8

[0071] The preparation process of Example 1 was followed, except that an equal molar amount of iron (III) p-toluenesulfonate was used to replace lutetium (III) trifluoromethanesulfonate as the catalyst, the solution polymerization temperature was 80 °C, and the reaction time was two days to obtain a random copolymer.

[0072] After testing, the SEC number average molecular weight of the polymer product prepared in this example is 16.6 kg / mol, the molar content of cyclohexene oxide is 0.10, the molar content of sarcosine residues is 0.90, the molecular weight distribution is 1.55, and the amino acid monomer conversion rate is 99%.

[0073] Example 9

[0074] The preparation process of Example 1 was followed, except that an equal molar amount of scandium (III) trifluoromethanesulfonate was used instead of lutetium (III) trifluoromethanesulfonate as the catalyst, the solution polymerization temperature was 80 °C, and the reaction time was two days to obtain a random copolymer.

[0075] After testing, the SEC number average molecular weight of the polymer product prepared in this example is 11.1 kg / mol, the molar content of cyclohexene oxide is 0.12, the molar content of sarcosine residues is 0.88, the molecular weight distribution is 1.88, and the amino acid monomer conversion rate is 99%.

[0076] Example 10

[0077] The preparation process of Example 1 was followed, except that an equal molar amount of iron (III) trifluoromethanesulfonate was used instead of lutetium (III) trifluoromethanesulfonate as the catalyst, the solution polymerization temperature was 80 °C, and the reaction time was two days to obtain a random copolymer.

[0078] After testing, the SEC number average molecular weight of the polymer product prepared in this example is 19.8 kg / mol, the molar content of cyclohexene oxide is 0.13, the molar content of sarcosine residues is 0.87, the molecular weight distribution is 1.53, and the amino acid monomer conversion rate is 99%.

[0079] Embodiment 11

[0080] The preparation process of Example 1 is followed, except that the molar ratio of sarcosine-NCA, cyclohexene oxide and catalyst is 100:400:1.

[0081] After testing, 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 rate of sarcosine-NCA monomer was 99%, and the molecular weight distribution was 1.77.

[0082] like Figure 4 As shown, the polymerization product (hydrophile-lipophile balance (HLB) = 11.7) can form nanoparticles with a particle size of about 400 nm in water and can be used as a solubilizer for fat-soluble drugs.

[0083] The above embodiments are preferred implementation modes of the present invention, but the implementation modes of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications that do not deviate from the spirit and principles of the present invention should be equivalent replacement methods and are included in the protection scope of the present invention.

Claims

1. A polypeptide ester ether amine random polymer, characterized in that: It has the following general structural formula: ； In the formula, R1 and R2 are independently selected from any one of hydrogen, C1-C12 saturated aliphatic hydrocarbon group, C1-C12 unsaturated aliphatic hydrocarbon group, aromatic hydrocarbon group, alkyl ether group, hydroxyalkyl group, C1-C6 hydroxyalkyl group with protected hydroxyl group, hydroxybenzyl group with protected hydroxyl group, alkyl thioether group, alkyl indolyl group, C1-C6 carboxyalkyl group with protected carboxyl group, and C1-C6 aminoalkyl group with protected amine group; or R1 and R2 together form tetrahydropyrrole, and the substituent is any one of hydroxytetrahydropyrrole with protected hydroxyl group; R3 and R4 are independently selected from any one of hydrogen, C1-C9 saturated aliphatic hydrocarbon group and C1-C9 unsaturated aliphatic hydrocarbon; or R3 and R4 together constitute cyclohexane, methyl, ethyl or vinyl substituted cyclohexane; x is selected from 0.30-0.99, and n is selected from 10-500.

2. The polypeptide ester ether amine random polymer according to claim 1, characterized in that The number average molecular weight of the polypeptide ester ether amine random polymer is 1-100 kg / mol, and the molecular weight distribution is below 2.

0.

3. The method for preparing a polypeptide ester ether amine random polymer according to claim 1 or 2, characterized in that: Using ML as a catalyst, a raw material comprising an α-amino acid-N-carboxylic anhydride monomer and an alkylene oxide monomer is subjected to solution polymerization to obtain the polypeptide ester ether amine random polymer; In the catalyst ML, M 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 the polypeptide ester ether amine random polymer according to claim 3, characterized in that: The structure of the α-amino acid-N-carboxylic anhydride monomer is shown in formula (I-1), and the structure of the alkylene oxide monomer is shown in formula (I-2); (I-1), (I-2); Wherein R1 and R2 are independently selected from any one of hydrogen, C1-C12 saturated aliphatic hydrocarbon group, C1-C12 unsaturated aliphatic hydrocarbon group, aromatic hydrocarbon group, alkyl ether group, hydroxyalkyl group, C1-C6 hydroxyalkyl group with protected hydroxyl group, hydroxybenzyl group with protected hydroxyl group, alkyl thioether group, alkyl indolyl group, C1-C6 carboxyalkyl group with protected carboxyl group, and C1-C6 aminoalkyl group with protected amine group; or R1 and R2 together form tetrahydropyrrole, and the substituent is any one of hydroxytetrahydropyrrole with protected hydroxyl group; R3 and R4 are independently selected from any one of hydrogen, C1-C9 saturated aliphatic hydrocarbon group and C1-C9 unsaturated aliphatic hydrocarbon; or R3 and R4 together constitute cyclohexane, methyl, ethyl or vinyl substituted cyclohexane.

5. The method for preparing the polypeptide ester ether amine random polymer according to claim 3, characterized in that: The α-amino acid-N-carboxylic acid anhydride monomer includes 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-acetyl hydroxyproline-NCA, O-benzyl tyrosine-NCA, and O-benzyldopa amino acid-NCA; The structure of the N-substituted glycine-NCA is shown in formula (I-3): （I-3）； wherein R5 is selected from a C2~C12 saturated aliphatic hydrocarbon group, a C2~C12 unsaturated aliphatic hydrocarbon group, an aromatic hydrocarbon group, an alkyl ether group, an alkyl thioether group, a C1~C6 carboxyalkyl group with a protected carboxyl group, or a C1~C6 aminealkyl group with a protected amino group; 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 ether amine random polymer according to claim 3, characterized in that: The catalyst ML includes 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 a polypeptide ester ether amine random polymer according to claim 3, characterized in that: The molar ratio of the α-amino acid-N-carboxylic anhydride monomer to the alkylene oxide monomer is 1:0.01 to 1:

100.

8. The method for preparing a polypeptide ester ether amine random polymer according to claim 3, characterized in that: The molar ratio of the catalyst to the monomer is 1:20 to 1:1000 based on 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 temperature is 10-100° C. and the time is 1-72 hours.

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

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