Poly-beta amino ester compound, and composition and application thereof

Abstract

The invention discloses a poly-beta amino ester compound, and a composition and application thereof. The invention provides a compound shown as a formula I or pharmaceutically acceptable salt thereof. The compound as shown in the formula I can be used for preparing a delivery system. The prepared delivery system can deliver nucleic acid drugs, and can be used for delivering nucleic acid prophylactic and / or therapeutic agents to the lung and / or liver. # imgabs0 #

Description

[0001] This application claims the priority of Chinese patent application No. 2023112753519 filed on September 28, 2023. This application cites the entire text of the above Chinese patent application. Technical Field

[0002] The invention relates to a poly-β-amino lipid compound, a composition and application thereof. Background Art

[0003] Gene therapy refers to inserting normal or therapeutic exogenous genes into target cells to repair defective genes in target cells or replace defective genes, thereby achieving the purpose of treating diseases. Gene therapy has demonstrated excellent performance in the fields of genetic diseases, cancer and infectious diseases, and has played a role that traditional drugs cannot replace. After the outbreak of the COVID-19 pandemic, nucleic acid drugs have played an important role in the fields of vaccines and infectious diseases. For nucleic acid drugs, how to design suitable vectors to deliver them to target cells is one of the biggest challenges restricting the development of nucleic acid drugs. Currently, the vectors used for nucleic acid delivery include viral vectors and non-viral vectors. Although viral vectors have high delivery efficiency, due to the rapid clearance of antibodies in the body, limited vector size and other possible side effects, researchers have recently been committed to developing non-viral delivery vectors, such as liposomes, polymers, inorganic materials, etc. The success of onpattro, the first non-viral vector siRNA drug, has also brought confidence in the design and development of non-viral nucleic acid delivery vectors.

[0004] Cationic polymers poly(beta-amino esters), PBAEs, have been studied in the field of nucleic acid delivery for more than two decades and are one of the most common materials used for gene delivery. Their electrostatic interactions with negatively charged nucleic acids are conducive to the formation of stable nanoparticles to deliver nucleic acids to target cells. PBAEs are usually prepared by step-growth polymerization (such as Michael addition reaction) or ring-opening polymerization, of which Michael addition reaction is the most commonly used reaction. The tertiary amines on the PBAEs backbone can be protonated to make the polymer positively charged, allowing lysosomal escape. PBAE can adjust the chemical structure and properties by changing the diacrylate, side chain, and end-capping groups.

[0005] In addition to the common characteristics of ionizable cationic lipids: effective nucleic acid coating, rapid cell uptake, efficient endosomal escape, easy release of nucleic acids into cells, and low cytotoxicity, PBAE also has unique advantages such as simple synthesis, strong modifiability, rich cargo types, and high stability. Currently, PBAE has achieved effective in vivo delivery of various nucleic acids such as mRNA, circular mRNA, shRNA, and plasmid DNA, and has achieved good results in the fields of cancer treatment, tumor immunity, and gene editing.

[0006] However, although PBAE has shown great advantages in nucleic acid delivery, based on literature research and previous laboratory studies, we found that traditional PBAE-encapsulated nucleic acids are basically limited to lung targeted expression when injected into mice via the tail vein; and in vivo experimental results in mice show that its lethal dose is low, the safety window is narrow, and the back-end application is limited; in addition, the expression level of traditional PBAE in the liver is still very limited, which is still far from the effectiveness of marketed ionizable lipids. Summary of the invention

[0007] In order to solve the problems that the existing PBAE compounds have low lethal doses in mice, narrow safety windows or limited back-end applications, the present invention aims to provide a poly-β-amino lipid compound, a composition and an application thereof.

[0008] The present invention provides a compound as shown in Formula I or a pharmaceutically acceptable salt thereof,

[0009]

[0010] Wherein, n is 2-20 (n represents the average degree of polymerization);

[0011] R is -(CH 2 )m- or by one or more R a Substituted -(CH 2 )m-, the -(CH 2 )0 to 12 -CH in m- 2 -optionally independently O, S, -NR b -, Sub-C 6 -C 12 Aryl, C 3 -C 6 Cycloalkyl, 1 or more R c Substituted sub-C 6 -C 12 Aryl and 9,9-diphenylfluorenyl are substituted, and m is 1-40;

[0012] Each R a are independently hydroxyl, -NR b R b , C 1 -C 6 Alkyl, halogen or C 1 -C 4 heteroalkyl; said C 1 -C 4 The heteroatom species in the heteroalkyl group is selected from one or more of O, S and N, and the number of heteroatoms is 1, 2 or 3;

[0013] Each R b are independently hydrogen, C1 -C 6 Alkyl, C 6 -C 12 Aryl, 1 or more R c Substituted C 6 -C 12 Aryl or one or more R b1 Substituted C 1 -C 6 alkyl;

[0014] Each R c are independently hydroxy, nitro, cyano, C 1 -C 6 Alkyl, halogen or amino;

[0015] Each R b1 are independently hydroxyl groups;

[0016] R 1 C 1 -C 22 Alkyl, C 2 -C 22 Alkenyl, C 2 -C 22 Alkynyl, with one or more R 1-1 Substituted C 1 -C 22 Alkyl, with one or more R 1-2 Substituted C 2 -C 22 Alkenyl or one or more R 1-3 Substituted C 2 -C 22 Alkynyl; the C 1 -C 22 0 to 8 -CH 2 - are optionally independently substituted by O or S; said C 2 -C 22 0 to 8 -CH 2 - are optionally independently substituted by O or S; said C 2 -C 22 0 to 8 -CH 2 - optionally independently substituted with O or S;

[0017] Each R 1-1 , R 1-2 and R 1-3 Independently -NR b R b , hydroxyl, C 6 -C 12 Aryl or C 3 -C 6 Cycloalkyl;

[0018] R 2 C 1 -C 22 Alkyl, C 2 -C 22 Alkenyl, C 2 -C 22 Alkynyl, with one or more R 2-1 Substituted C 1 -C 22 Alkyl, with one or more R 2-2 Substituted C 2 -C 22 Alkenyl, one or more R 2-3 Substituted C 2 -C 22 Alkynyl, C 3 -C 6 Cycloalkyl, 1 or more R 2e Substituted C 3 -C 6 Cycloalkyl, "a 3-7 membered heterocycloalkyl group having 1, 2 or 3 heteroatoms selected from N, O and S" or "a 3-7 membered heterocycloalkyl group having 1, 2 or 3 heteroatoms ... 2f The substituted "heteroatom is selected from 1, 2 or 3 of N, O and S, and the number of heteroatoms is 1, 2 or 3 3-membered heterocycloalkyl", the C 2 -C 22 0 to 8 -CH 2 - optionally substituted by O or S;

[0019] Each R 2-1 , R 2-2 and R 2-3 Independently -NR b R b , hydroxyl, C 6 -C 12 Aryl, one or more R 2d3 Substituted C 6 -C 12 Aryl, C 3 -C 6 Cycloalkyl, with one or more R 2d3 Substituted C 3 -C 6 Cycloalkyl, "a 5-10 membered heteroaryl group having 1, 2 or 3 heteroatoms selected from N, O and S" or "a 5-10 membered heteroaryl group having 1, 2 or 3 heteroatoms ... 2d3 Substituted "5-10 membered heteroaryl group having 1, 2 or 3 heteroatoms selected from N, O and S";

[0020] Each R2d3 Independently for C 1 -C 6 Alkyl, halogen or halogenated C 1 -C 6 alkyl;

[0021] Each R 2e and R 2f are independently halogen, C 1 -C 6 Alkyl or halogenated C 1 -C 6 alkyl;

[0022] X is

[0023] R 3 For hydrogen, C 1 -C 22 Alkyl, C 2 -C 22 Alkenyl, C 2 -C 22 Alkynyl, with one or more R 3-1 Substituted C 1 -C 22 Alkyl, with one or more R 3-2 Substituted C 2 -C 22 Alkenyl, one or more R 3-3 Substituted C 2 -C 22 Alkynyl, C 3 -C 6 Cycloalkyl, C 6 -C 12 Aryl or "3-7 membered heterocycloalkyl group whose heteroatoms are selected from 1, 2 or 3 of N, O and S, and whose heteroatoms are 1, 2 or 3";

[0024] Each R 3-1 , R 3-2 and R 3-3 Independently -NR b R b , C 3 -C 6 Cycloalkyl or hydroxy.

[0025] In a preferred embodiment, the present invention provides a compound as shown in Formula I or a pharmaceutically acceptable salt thereof,

[0026]

[0027] in,

[0028] n is 2-20 (n represents the average degree of polymerization);

[0029] R is -(CH 2 )m- or by one or more R a Substituted -(CH 2 )m-, the -(CH 2 )0 to 10 -CH 2 -Optionally O, S, -NR b -, Sub-C 6 -C 12 Aryl, C 3 -C 6 Cycloalkyl and 1 or more R c Substituted sub-C 6 -C 12 Aryl, m is 1-30;

[0030] Each R a are independently hydroxyl, -NR b R b , C 1 -C 6 Alkyl, halogen or C 1 -C 4 heteroalkyl; said C 1 -C 4 The heteroatom species in the heteroalkyl group is selected from one or more of O, S and N, and the number of heteroatoms is 1, 2 or 3;

[0031] Each R b are independently hydrogen, C 1 -C 6 Alkyl, C 6 -C 12 Aryl or 1 or more R c Substituted C 6 -C 12 Aryl;

[0032] Each R c are independently hydroxy, nitro, cyano, C 1 -C 6 Alkyl, halogen or amino;

[0033] R 1 C 1 -C 22 Alkyl, C 2 -C 22 Alkenyl, C 2 -C 22 Alkynyl, with one or more R 1-1 Substituted C 1 -C 22 Alkyl, with one or more R 1-2 Substituted C 2 -C 22Alkenyl or one or more R 1-3 Substituted C 2 -C 22 Alkynyl;

[0034] Each R 1-1 , R 1-2 and R 1-3 Independently -NR b R b - or hydroxyl group;

[0035] R 2 C 1 -C 22 Alkyl, C 2 -C 22 Alkenyl, C 2 -C 22 Alkynyl, with one or more R 2-1 Substituted C 1 -C 22 Alkyl, with one or more R 2-2 Substituted C 2 -C 22 Alkenyl or one or more R 2-3 Substituted C 2 -C 22 Alkynyl;

[0036] Each R 2-1 , R 2-2 and R 2-3 Independently -NR b R b or hydroxyl;

[0037] X is

[0038] R 3 For hydrogen, C 1 -C 22 Alkyl, C 2 -C 22 Alkenyl, C 2 -C 22 Alkynyl, with one or more R 3-1 Substituted C 1 -C 22 Alkyl, with one or more R 3-2 Substituted C 2 -C 22 Alkenyl, one or more R 3-3 Substituted C 2 -C 22 Alkynyl, C 3 -C 6 Cycloalkyl, C 6 -C 12Aryl or a 3-7-membered heterocycloalkyl group optionally substituted by 1, 2 or 3 heteroatoms, wherein the heteroatoms are optionally one or more of N, O and S; the number of heteroatoms is 1, 2 or 3;

[0039] Each R 3-1 , R 3-2 and R 3-3 Independently -NR b R b , C 3 -C 6 Cycloalkyl or hydroxy.

[0040] Those skilled in the art will appreciate that the -(CH 2 )0 to 10 -CH 2 - is optionally substituted by O, etc., which has the same meaning as the -(CH 2 )0 to 10 -CH 2 - is optionally substituted by O, etc., the -(CH 2 )m- means "-(CH 2 )m-" and "by one or more R a Substituted -(CH 2 )m-" 2 )m-", does not specifically refer to unsubstituted -(CH 2 )m-.

[0041] In a preferred embodiment, such as in the compound of formula I, the definitions of certain groups may be as described below, and the definitions of other groups may be as described in any other embodiment (hereinafter referred to as "a preferred embodiment").

[0042] In a preferred embodiment, in R, the -(CH 2 )m-, m can be 1-27, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 12, 14, 15, 23 or 27.

[0043] In a preferred embodiment, in R, the a Substituted -(CH 2 )m-, the plurality is 2-14, for example, 2, 3, 4, 5, 6, 7, 8 or 12.

[0044] In a preferred embodiment, in R, the a Substituted -(CH 2 )m-, the plurality is 2-8, for example, 2, 3, 4, 5, 6, 7 or 8.

[0045] In a preferred embodiment, in R, the -(CH 2)0 to 12 -CH in m- 2 -Optionally independently O, S, -NR b -, Sub-C 6 -C 12 Aryl, C 3 -C 6 Cycloalkyl, 1 or more R c Substituted sub-C 6 -C 12 The aryl and 9,9-diphenylfluorenyl groups are replaced by the -(CH 2 )1 to 13 -CH in m- 2 - is optionally substituted by O, m may be 5-36, for example

[0046] In a preferred embodiment, in R, the -(CH 2 )0 to 10 -CH 2 -Optionally O, S, -NR b -, Sub-C 6 -C 12 Aryl and 1 or more R c Substituted sub-C 6 -C 12 Aryl is the -(CH 2 )1 to 6 -CH in m- 2 - optionally substituted with O, m may be 5-27, for example

[0047]

[0048] In a preferred embodiment, in R, the -(CH 2 )0 to 12 -CH in m- 2 -optionally independently O, S, -NR b -, Sub-C 6 -C 12 Aryl, C 3 -C 6 Cycloalkyl, 1 or more R c Substituted sub-C 6 -C 12 The aryl and 9,9-diphenylfluorenyl groups are replaced by the -(CH 2 )1 to 2 -CH in m- 2 - is optionally substituted by S, m may be 1-6, for example

[0049] In a preferred embodiment, in R, the -(CH 2 )0 to 10 -CH2 -Optionally O, S, -NR b -, Sub-C 6 -C 12 Aryl and 1 or more R c Substituted sub-C 6 -C 12 Aryl is the -(CH 2 )1 to 2 -CH in m- 2 - optionally substituted with S, m may be 1-6, for example

[0050] In a preferred embodiment, in R, the -(CH 2 )0 to 12 -CH in m- 2 -optionally independently O, S, -NR b -, Sub-C 6 -C 12 Aryl, C 3 -C 6 Cycloalkyl, 1 or more R c Substituted sub-C 6 -C 12 The aryl and 9,9-diphenylfluorenyl groups are replaced by the -(CH 2 )1 to 2 -CH in m- 2 -Optionally sub-C 6 -C 12 Aryl or 1 or more R c Substituted sub-C 6 -C 12 Aryl substitution, m can be 1-6, for example

[0051] In a preferred embodiment, in R, the -(CH 2 )0 to 10 -CH 2 -Optionally O, S, -NR b -, Sub-C 6 -C 12 Aryl and 1 or more R c Substituted sub-C 6 -C 12 Aryl is the -(CH 2 )1 to 2 -CH in m- 2 -Optionally sub-C 6 -C 12 Aryl and / or 1 or more R c Substituted sub-C 6 -C 12 Aryl substitution, m can be 1-6, for example

[0052] In a preferred embodiment, in R, the -(CH 2 )0 to 12 -CH in m- 2 -optionally independently O, S, -NR b -, Sub-C 6 -C 12 Aryl, C 3 -C 6 Cycloalkyl, 1 or more R c Substituted sub-C 6 -C 12 The aryl and 9,9-diphenylfluorenyl groups are replaced by the -(CH 2 )1 to 6 -CH in m- 2 -Optionally O and C 6 -C 12 Aryl substitution, e.g.

[0053]

[0054] In a preferred embodiment, in R, the -(CH 2 )0 to 10 -CH 2 -Optionally O, S, -NR b -, Sub-C 6 - C 12 Fang The base and is 1 or more R c Substituted sub-C 6 -C 12 Aryl is the -(CH 2 )1 to 6 -CH in m- 2 -Optionally O and C 6 -C 12 Aryl and / or 1 or more R c Substituted sub-C 6 -C 12 Aryl substitution, e.g.

[0055]

[0056] In a preferred embodiment, in R, the sub-C 6 -C 12 The aryl group is C 6 -C 10 An aryl group, for example, phenylene.

[0057] In a preferred embodiment, R a In the C 1 -C 6 The alkyl group is C 1 -C 4 The alkyl group, for example, methyl, ethyl.

[0058] In a preferred embodiment, R a In the above, the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine.

[0059] In a preferred embodiment, each Ra In the C 1 -C 4 The heteroatom type in the heteroalkyl group is O, S or N, such as O; the number of heteroatoms can be 2; for example

[0060] In a preferred embodiment, R a In the C 1 -C 4 The heteroalkyl group is C 4 of heteroalkyl.

[0061] In a preferred embodiment, R b In the C 1 -C 6 Alkyl is C 1 -C 4 Alkyl, for example, methyl or ethyl.

[0062] In a preferred embodiment, R b In the C 1 -C 6 The alkyl group is C 1 -C 4 An alkyl group, for example, a methyl group.

[0063] In a preferred embodiment, R b In the C 6 -C 12 The aryl group is C 6 -C 10 An aryl group, for example, a phenyl group.

[0064] In a preferred embodiment, R b In the above, the one or more R b1 Substituted C 1 -C 6 C in the alkyl group 1 -C 6 Alkyl is C 1 -C 4 An alkyl group; for example, ethyl.

[0065] In a preferred embodiment, R c In the C 1 -C 6 The alkyl group is C 1 -C 4 An alkyl group, for example, a methyl group.

[0066] In a preferred embodiment, R c In the above, the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine.

[0067] In a preferred embodiment, R 1 In the C1 -C 22 The alkyl group is C 2 -C 20 An alkyl group, preferably a straight chain C 2 -C 20 The alkyl group, for example,

[0068]

[0069] In a preferred embodiment, R 1 In the C 2 -C 22 Alkenyl is C 14 -C 22 Alkenyl, preferably a straight chain C 14 -C 22 Alkenyl, for example,

[0070] In a preferred embodiment, R 1 In the C 2 -C 22 Alkynyl is a straight chain C 2 -C 20 Alkynyl groups, for example,

[0071] In a preferred embodiment, R 1 In the C 2 -C 22 0 to 8 -CH 2 - optionally independently replaced by O or S as the C 2 -C 22 0 to 8 -CH 2 - is optionally substituted with O; for example,

[0072] In a preferred embodiment, R 1-1 In the C 6 -C 12 Aryl is phenyl.

[0073] In a preferred embodiment, R 1-1 In the C 3 -C 6 Cycloalkyl is cyclohexyl.

[0074] In a preferred embodiment, R 2 In the C 1 -C 22 The alkyl group is C 2 -C 20 The alkyl group, for example,

[0075]

[0076] In a preferred embodiment, R 2 In the C 1 -C 22 The alkyl group is C 2 -C 20 An alkyl group, preferably a straight chain C 2 -C 20 The alkyl group, for example,

[0077]

[0078] In a preferred embodiment, R 2 In the C 2 -C 22 The alkenyl groups are independently C 2 -C 22 Alkenyl, preferably a straight chain C 2 -C 10 Alkenyl, for example,

[0079]

[0080] In a preferred embodiment, R 2 In the C 2 -C 22 Alkenyl is C 14 -C 22 Alkenyl, preferably a straight chain C 14 -C 22 Alkenyl, for example,

[0081]

[0082]

[0083] In a preferred embodiment, R 2 In the C 2 -C 22 Alkynyl is C 2 -C 6 Alkynyl, preferably a straight chain C 2 -C 6 Alkynyl groups, for example,

[0084] In a preferred embodiment, R 2 In the C 2 -C 22 0 to 8 -CH 2 - optionally replaced by O or S 2 -C 220 to 8 -CH 2 - is optionally replaced by O; for example,

[0085] In a preferred embodiment, R 2 In the above, the one or more R 2-1 Substituted C 1 -C 22 The alkyl group may be 2-1 Substituted C 1 -C 6 Alkyl groups, for example,

[0086] In a preferred embodiment, R 2 In the above, the one or more R 2-1 Substituted C 1 -C 22 The alkyl group may be 2-1 Substituted C 3 -C 6 Alkyl groups, for example,

[0087] In a preferred embodiment, R 2 In the C 3 -C 6 Cycloalkyl is cyclohexyl.

[0088] In a preferred embodiment, R 2 In the heterocycloalkyl group of the 3-7 membered ring, the heteroatom is N or O; for example,

[0089] In a preferred embodiment, R 2-1 In the C 6 -C 12 Aryl is phenyl.

[0090] In a preferred embodiment, R 2-1 In the above, the one or more R 2d3 Substituted C 6 -C 12 Aryl is an aryl group consisting of one or more R 2d3 Substituted C 6 -C 12 Aryl; for example,

[0091] In a preferred embodiment, R 2-1 In the C 3 -C 6 Cycloalkyl is cyclohexyl.

[0092] In a preferred embodiment, R2-1 In the above, the “heteroatoms are selected from 1, 2 or 3 of N, O and S, and the number of heteroatoms is 1, 2 or 3 5-10 membered heteroaryl” is a 5-membered heteroaryl substituted by O, for example,

[0093] In a preferred embodiment, R 2d3 In the above, the halogen is fluorine, chlorine, bromine or iodine, for example, bromine.

[0094] In a preferred embodiment, R 2f In the C 1 -C 6 The alkyl groups are independently C 1 -C 4 An alkyl group; for example, a methyl group.

[0095] In a preferred embodiment, the halogenated C 1 -C 6 In the alkyl group, halo is substituted by halogen, wherein the halogen is fluorine, chlorine, bromine or iodine; 1 -C 6 Alkyl is C 1 -C 4 alkyl.

[0096] In a preferred embodiment, R 3 In the C 1 -C 22 The alkyl group may be C 1 -C 6 Alkyl groups, for example,

[0097] In a preferred embodiment, R 3 In the C 1 -C 22 The alkyl group may be C 1 -C 4 Alkyl groups, for example,

[0098] In a preferred embodiment, R 3 In the C 2 -C 22 Alkenyl is C 2 -C 4 Alkenyl, for example,

[0099] In a preferred embodiment, R 3 In the above, the one or more R 3-1 Substituted C 1 -C 22 The alkyl group may be 3-1 Substituted C 1 -C3 Alkyl groups, for example,

[0100] In a preferred embodiment, R 3-1 In, C 3 -C 6 The cycloalkyl group may be

[0101] In a preferred embodiment, n is 5-12.

[0102] In a preferred embodiment, n may be 8-11.

[0103] In a preferred embodiment, R is -(CH 2 )m- or by one or more R a Substituted -(CH 2 )m-; said-(CH 2 )0 to 12 -CH in m- 2 -Optionally O, S, C 6 -C 12 Aryl, 1 or more R c Substituted sub-C 6 -C 12 Aryl and 9,9-diphenylfluorenyl are substituted, and m is 1-27, for example,

[0104] Preferably, R is -(CH 2 )m- or by one or more R a Substituted -(CH 2 )m-; said-(CH 2 )m-satisfies any of the following conditions: (1)-(CH 2 )1 to 12 -CH in m- 2 - is optionally substituted by O; (2) the -(CH 2 )1 to 6 -CH in m- 2 - optionally independently O and C 6 -C 12 Aryl substitution; for example, R is

[0105]

[0106] For example, R is For example, R is

[0107] In a preferred embodiment, R is -(CH 2 )m-, the -(CH2 )0 -CH in m- 2 - has been replaced.

[0108] In a preferred embodiment, R is -(CH 2 )m- or by one or more R a Substituted -(CH 2 )m-; said-(CH 2 )0 to 10 -CH 2 -Optionally O, S, C 6 -C 12 Aryl and 1 or more R c Substituted sub-C 6 -C 12 Aryl substituted, m is 1-27, for example,

[0109] Preferably, R is -(CH 2 )m- or 1-4 R a Substituted -(CH 2 )m-; said-(CH 2 )0 to 4 -CH in m- 2 -Optionally O and C 6 -C 12 Aryl substituted, m is 3-11; for example, For example, For example, Further example,

[0110]

[0111] In a preferred embodiment, each R a are independently hydroxyl, C 1 -C 6 Alkyl, halogen or C 1 -C 4 heteroalkyl; said C 1 -C 4 The heteroatom species in the heteroalkyl group is O, S or N, and the number of heteroatoms is 1, 2 or 3; preferably, each R a are independently hydroxyl or C 1 -C 6 alkyl.

[0112] In a preferred embodiment, each R c are independently nitro or C 1 -C 6 alkyl.

[0113] In a preferred embodiment, R 1 C 1 -C 22 Alkyl, C 2 -C 22 Alkenyl, C 2 -C 22 Alkynyl or one or more R 1-1 Substituted C 1 -C 22 Alkyl, the C 2 -C 22 0 to 5 -CH 2 - is optionally substituted with O; for example,

[0114]

[0115] Preferably, R 1 C 8 -C 18 Alkyl, C 3 -C 18 Alkenyl, C 3 -C 18 Alkynyl or one or more R 1-1 Substituted C 1 -C 6 Alkyl, the C 2 -C 22 0 to 5 -CH 2 - is optionally substituted with O; for example,

[0116] More preferably, R 1 C 8 -C 18 Alkyl groups, such as R 1 for For example, R 1 for

[0117]

[0118] In a preferred embodiment, R 1 C 1 -C 22 Alkyl or C 2 -C 22 Alkenyl, for example,

[0119] Preferably, R 1 C 8 -C 18 Alkyl groups, for example,

[0120] In a preferred embodiment, each R 1-1 For-NR b R b , hydroxyl, C 6 -C 12 Aryl or C 3 -C 6 Cycloalkyl.

[0121] In a preferred embodiment, R 2 C 1 -C 22 Alkyl, C 2 -C 22 Alkenyl, C 2 -C 22 Alkynyl, with one or more R 2-1 Substituted C 1 -C 22 Alkyl, C 3 -C 6 Cycloalkyl, "a 3-7 membered heterocycloalkyl group having 1, 2 or 3 heteroatoms selected from N, O and S" or "a 3-7 membered heterocycloalkyl group having 1, 2 or 3 heteroatoms ... 2f The substituted "heteroatom is selected from 1, 2 or 3 of N, O and S, and the number of heteroatoms is 1, 2 or 3 3-membered heterocycloalkyl", the C 2 -C 22 0 to 5 -CH 2 - is optionally substituted with O; for example,

[0122] Preferably, R 2 C 1 -C 18 Alkyl, C 3 -C 18 Alkenyl, C 3 -C 18 Alkynyl, with one R 2 -1 Substituted C 1 -C 6 Alkyl, C 3 -C 6Cycloalkyl, "a 3-7 membered heterocycloalkyl group having 1, 2 or 3 heteroatoms selected from N, O and S" or "a 3-7 membered heterocycloalkyl group having 1, 2 or 3 heteroatoms ... 2f The substituted "heteroatom is selected from 1, 2 or 3 of N, O and S, and the number of heteroatoms is 1, 2 or 3 3-membered heterocycloalkyl", the C 2 -C 22 0 to 5 -CH 2 - is optionally substituted with O; for example,

[0123] More preferably, R 2 C 1 -C 22 Alkyl or one or more R 2-1 Substituted C 1 -C 22 Alkyl, each R 2-1 are independently hydroxyl.

[0124] In a preferred embodiment, R 2 C 1 -C 22 Alkyl, C 2 -C 22 Alkenyl or one or more R 2-1 Substituted C 1 -C 22 Alkyl groups, for example,

[0125]

[0126] Preferably, R 2 C 4 -C 18 Alkyl or an R 2-1 Substituted C 1 -C 5 Alkyl groups, for example,

[0127] In a preferred embodiment, R 2-1 For-NR b R b , hydroxyl, C 6 -C 12 Aryl, one or more R 2d3 Substituted C 6 -C 12 Aryl, C 3 -C 6Cycloalkyl or "a 5-10 membered heteroaryl group wherein the heteroatom is selected from 1, 2 or 3 of N, O and S and the number of the heteroatom is 1, 2 or 3".

[0128] In a preferred embodiment, R 2-1 For-NR b R b or hydroxyl.

[0129] In a preferred embodiment, each R b are independently hydrogen, C 1 -C 6 Alkyl, C 6 -C 12 Aryl or one or more R b1 Substituted C 1 -C 6 alkyl.

[0130] In a preferred embodiment, each R b are independently hydrogen or C 1 -C 6 alkyl.

[0131] In a preferred embodiment, each R 2d3 are independently halogen.

[0132] In a preferred embodiment, each R 2e and R 2f Independently for C 1 -C 6 alkyl.

[0133] In a preferred embodiment, X is For example, X is

[0134] In a preferred embodiment, X is Preferably, X is

[0135] In a preferred embodiment, R 3 For hydrogen, C 1 -C 22 Alkyl, with one or more R 3-1 Substituted C 1 -C 22 Alkyl or C 2 -C 22 alkenyl, for example, hydrogen, Preferably, R 3 For hydrogen, C 1 -C 22 Alkyl or C 2 -C 22 alkenyl, for example, hydrogen,

[0136] In a preferred embodiment, R 3 For hydrogen, C 1 -C 22 Alkyl or one or more R 3-1 Substituted C 1 -C 22 Alkyl groups, for example, For example, R 3 For hydrogen.

[0137] In a preferred embodiment, R 3-1 C 3 -C 6 Cycloalkyl.

[0138] In a preferred embodiment, n is 5-15, such as 8-15.

[0139] In a preferred embodiment, n is 5-12.

[0140] In a preferred embodiment, R is -(CH 2 )m- or by one or more R a Substituted -(CH 2 )m-; said-(CH 2 )0 to 12 -CH in m- 2 - are optionally independently substituted by O, m is 1-19, for example,

[0141] For example, Preferably, R is -(CH 2 )m-; m is 1-6, for example, For example,

[0142] In a preferred embodiment, R is -(CH 2 )m-, the -(CH 2 )0 to 3 -CH in m- 2 - is optionally substituted by O, m is 1-12; for example,

[0143] In a preferred embodiment, each R a Independently for C 1 -C 6 alkyl.

[0144] In a preferred embodiment, R is -(CH 2 )m- or 1-4 R a Substituted -(CH 2)m-; said-(CH 2 )0 to 4 -CH in m- 2 -Optionally O and C 6 -C 12 Aryl substituted, m is 3-11; for example, For example,

[0145] In a preferred embodiment, R is -(CH 2 )m-; said-(CH 2 )0 to 3 -CH in m- 2 - is optionally substituted with O, m is 4-11; for example, For example,

[0146] In a preferred embodiment, R is -(CH 2 )m-; said-(CH 2 )0 to 3 -CH in m- 2 - is optionally substituted with O, m is 4-11; for example,

[0147] In a preferred embodiment, R 1 C 1 -C 22 Alkyl or C 2 -C 22 Alkenyl; for example,

[0148] For example,

[0149]

[0150] Further, for example, More for example,

[0151] In a preferred embodiment, R 1 C 10 -C 16 Alkyl groups, for example,

[0152] In a preferred embodiment, R 2 C 1 -C 22 Alkyl, C 2 -C22 Alkenyl, C 2 -C 22 Alkynyl, with one R 2-1 Substituted C 1 -C 6 Alkyl, C 3 -C 6 Cycloalkyl, "a 3-7 membered heterocycloalkyl group having 1, 2 or 3 heteroatoms selected from N, O and S" or "a 3-7 membered heterocycloalkyl group having 1, 2 or 3 heteroatoms ... 2f Substituted "3-7 membered heterocycloalkyl group having 1, 2 or 3 heteroatoms selected from N, O and S"; for example,

[0153] Better, R 2 C 1 - C 12 Alkyl, C 2 -C 22 Alkenyl, C 2 -C 22 Alkynyl, with one R 2-1 Substituted C 1 -C 6 Alkyl, C 3 -C 6 Cycloalkyl or heteroatom Selected from N, 1, 2 or 3 of O and S, and 3- to 7-membered heterocycloalkyl having 1, 2 or 3 heteroatoms”; for example,

[0154] For example,

[0155] In a preferred embodiment, R 2 C 1 -C 22 Alkyl, C 2 -C 22 Alkenyl, C 2 -C 22 Alkynyl, with one R 2-1 Substituted C 1 -C 22 Alkyl, C 3 -C 6 Cycloalkyl or 1 or more R 2f Substituted "3-7 membered heterocycloalkyl group having 1, 2 or 3 heteroatoms selected from N, O and S"; for example,

[0156] In a preferred embodiment, R 2 C 1 -C 22 Alkyl, C 2 -C 22 Alkenyl, with one R 2-1 Substituted C1 -C 6 Alkyl or 1 or more R 2f Substituted "3-7 membered heterocycloalkyl group having 1, 2 or 3 heteroatoms selected from N, O and S"; for example,

[0157] In a preferred embodiment, R 2 C 1 -C 22 Alkyl, C 2 -C 22 Alkenyl or one or more R 2-1 Substituted C 1 -C 22 Alkyl; for example,

[0158] In a preferred embodiment, R 2-1 For-NR b R b , hydroxyl, C 6 -C 12 Aryl, one or more R 2d3 Substituted C 6 -C 12 Aryl or "a 5-10 membered heteroaryl group having 1, 2 or 3 heteroatoms selected from N, O and S"; for example, -NR b R b , hydroxyl, C 6 -C 12 Aryl or one or more R 2d3 Substituted C 6 -C 12 Aryl; also for example, -NR b R b .

[0159] In a preferred embodiment, each R b Independently for C 1 -C 6 alkyl.

[0160] In a preferred embodiment, R 2 C 4 -C 16 Alkyl or an R 2-1 Substituted C 1 -C 5 Alkyl groups, for example,

[0161] In a preferred embodiment, R 2-1 It is hydroxyl.

[0162] In a preferred embodiment, R 2 C 4 -C 16 Alkyl or an R 2-1 Substituted C 1 -C 5 Alkyl groups, for example,

[0163] In a preferred embodiment, n is 8-9.

[0164] In a preferred embodiment, R is -(CH 2 )m-; m is 4-6; for example,

[0165] In a preferred embodiment, R 1 C 14 -C 16 Alkyl groups, for example,

[0166] In a preferred embodiment, R 2 C 4 -C 16 Alkyl or an R 2-1 Substituted C 1 -C 5 Alkyl groups, for example,

[0167] For example, For example,

[0168] In a preferred embodiment, n is 9-10.

[0169] In a preferred embodiment, R is -(CH 2 )m-; said-(CH 2 )0 to 3 -CH in m- 2 - is optionally substituted with O, m is 4-11; for example,

[0170] In a preferred embodiment, R 1 C 8 -C 12 Alkyl groups, for example,

[0171] In a preferred embodiment, R 2 C 4 -C 10 Alkyl or an R 2-1 Substituted C 1 -C 5Alkyl groups, for example, For example,

[0172] In a preferred embodiment, the weight average molecular weight of the compound as shown in Formula I is 1000-10000.

[0173] In a preferred embodiment,

[0174] R is -(CH 2 )m-, m is 1-6; for example,

[0175] R 1 C 8 -C 18 Alkyl groups, such as R 1 for

[0176] In one plan,

[0177] R is -(CH 2 )m-, the -(CH 2 )0 to 6 -CH in m- 2 - are optionally independently substituted by O, m is 8-14, for example,

[0178] R 1 C 8 -C 18 Alkyl groups, such as R 1 for

[0179] In one scheme, n is 8-11;

[0180] R is -(CH 2 )m- or by one or more R a Substituted -(CH 2 )m-; said-(CH 2 )0 to 10 -CH 2 -Optionally O, S, C 6 -C 12 Aryl and 1 or more R c Substituted sub-C 6 -C 12 Aryl substituted, m is 1-27, for example,

[0181]

[0182] Each R a are independently hydroxyl, C1 -C 6 Alkyl, halogen or C 1 -C 4 heteroalkyl; said C 1 -C 4 The heteroatom type in the heteroalkyl group is O, S or N, and the number of heteroatoms is 1, 2 or 3;

[0183] Each R c are independently nitro or C 1 -C 6 alkyl;

[0184] R 1 C 1 -C 22 Alkyl or C 2 -C 22 Alkenyl, for example,

[0185]

[0186] R 2 C 1 -C 22 Alkyl, C 2 -C 22 Alkenyl or one or more R 2-1 Substituted C 1 -C 22 Alkyl groups, for example,

[0187] R 2-1 For-NR b R b or hydroxyl;

[0188] Each R b are independently hydrogen or C 1 -C 6 alkyl;

[0189] X is

[0190] R 3 For hydrogen, C 1 -C 22 Alkyl or one or more R 3-1 Substituted C 1 -C 22 Alkyl groups, for example,

[0191] R 3-1 C 3 -C6 Cycloalkyl;

[0192] Preferably, the weight average molecular weight of the compound as shown in Formula I is 2030-5460, preferably 2600-4200, for example, 2600, 2700, 2900, 3000, 3100, 3400, 3500, 4100 or 4200.

[0193] In one scheme, n is 8-11;

[0194] R is -(CH 2 )m- or 1-4 R a Substituted -(CH 2 )m-; said-(CH 2 )0 to 4 -CH in m- 2 -Optionally O and C 6 -C 12 Aryl substituted, m is 3-11; for example,

[0195] Each R a are independently hydroxyl or C 1 -C 6 alkyl;

[0196] R 1 C 8 -C 18 Alkyl groups, for example,

[0197] R 2 C 4 -C 18 Alkyl or an R 2-1 Substituted C 1 -C 5 Alkyl groups, for example,

[0198] R 2-1 For-NR b R b or hydroxyl;

[0199] Each R b are independently hydrogen or C 1 -C 6 alkyl;

[0200] X is

[0201] R 3 is hydrogen;

[0202] Preferably, the weight average molecular weight of the compound as shown in Formula I is 2030-5460, preferably 2600-4200, for example, 2600, 2700, 2900, 3000, 3100, 3400, 3500, 4100 or 4200.

[0203] In one scheme, n is 8-11;

[0204] R is -(CH 2 )m- or 1-4 R a Substituted -(CH 2 )m-; said-(CH 2 )0 to 4 -CH in m- 2 -Optionally O and C 6 -C 12 Aryl substituted, m is 3-11; for example,

[0205] Each R a are independently hydroxyl or C 1 -C 6 alkyl;

[0206] R 1 C 8 -C 18 Alkyl groups, for example,

[0207] R 2 C 4 -C 18 Alkyl or an R 2-1 Substituted C 1 -C 5 Alkyl groups, for example,

[0208] R 2-1 For-NR b R b or hydroxyl;

[0209] Each R b are independently hydrogen or C 1 -C 6 alkyl;

[0210] X is

[0211] R 3 is hydrogen;

[0212] Preferably, the weight average molecular weight of the compound as shown in Formula I is 1890-5330, preferably 2700-4100, for example, 2700, 3100, 3500 or 4100.

[0213] In one scheme, n is 8-11;

[0214] R is -(CH 2 )m- or 1-4 R a Substituted -(CH 2 )m-; said-(CH 2 )0 to 4 -CH in m- 2 -Optionally O and C 6 -C 12 Aryl substituted, m is 3-11; for example,

[0215] Each R a are independently hydroxyl or C 1 -C 6 alkyl;

[0216] R 1 C 8 -C 18 Alkyl groups, for example,

[0217] R 2 C 4 -C 18 Alkyl or an R 2-1 Substituted C 1 -C 5 Alkyl groups, for example,

[0218] R 2-1 For-NR b R b or hydroxyl;

[0219] Each R b are independently hydrogen or C 1 -C 6 alkyl;

[0220] X is

[0221] R 3 is hydrogen;

[0222] Preferably, the weight average molecular weight of the compound as shown in Formula I is 1890-4550, preferably 2700-3500, for example, 2700, 3100 or 3500.

[0223] In one scheme, n is 8-11;

[0224] R is -(CH 2 )m- or 1-4 R a Substituted -(CH 2 )m-; said-(CH 2 )0 to 4 -CH in m- 2 -Optionally O and C 6 -C 12 Aryl substituted, m is 3-11; for example,

[0225] Each R a are independently hydroxyl or C 1 -C 6 alkyl;

[0226] R 1 C 8 -C 18 Alkyl groups, for example,

[0227] R 2 C 4 -C 18 Alkyl or an R 2-1 Substituted C 1 -C 5 Alkyl groups, for example,

[0228] R 2-1 For-NR b R b or hydroxyl;

[0229] Each R b are independently hydrogen or C 1 -C 6 Alkyl; X is

[0230] R 3 For hydrogen.

[0231] In one plan,

[0232] n is 8-11;

[0233] R is -(CH 2 )m- or 1-4 R a Substituted -(CH 2 )m-; said-(CH 2 )0 to 4 -CH in m- 2 -Optionally O and C 6 -C 12Aryl substituted, m is 3-11; for example,

[0234] Each R a are independently hydroxyl or C 1 -C 6 alkyl;

[0235] R 1 C 8 -C 18 Alkyl groups, for example,

[0236] R 2 C 4 -C 18 Alkyl or an R 2-1 Substituted C 1 -C 5 Alkyl groups, for example,

[0237] R 2-1 For-NR b R b or hydroxyl;

[0238] Each R b are independently hydrogen or C 1 -C 6 alkyl;

[0239] X is

[0240] R 3 is hydrogen;

[0241] Preferably, the weight average molecular weight of the compound as shown in Formula I is 2030-5460, preferably 2600-4200, for example, 2600, 2700, 2900, 3000, 3100, 3400, 3500 or 4200.

[0242] In one scheme, n is 8-11;

[0243] R is -(CH 2 )m- or 1-4 R a Substituted -(CH 2 )m-; said-(CH 2 )0 to 4 -CH in m- 2 -Optionally O and C 6 -C 12 Aryl substituted, m is 3-11; for example,

[0244] Each R a are independently hydroxyl or C 1 -C 6 alkyl;

[0245] R 1 C 8 -C 18 Alkyl groups, for example,

[0246] R 2 C 4 -C 18 Alkyl or an R 2-1 Substituted C 1 -C 5 Alkyl groups, for example,

[0247]

[0248] R 2-1 For-NR b R b or hydroxyl;

[0249] Each R b are independently hydrogen or C 1 -C 6 alkyl;

[0250] X is

[0251] R 3 is hydrogen;

[0252] Preferably, the weight average molecular weight of the compound as shown in Formula I is 2030-5460, preferably 2600-4200, for example, 2600, 2900, 3000, 3100, 3400 or 4200.

[0253] In one scheme, n is 8-11;

[0254] R is -(CH 2 )m-; said-(CH 2 )0 to 3 -CH in m- 2 - is optionally substituted with O, m is 4-11; for example,

[0255] R 1 C 8 -C 18 Alkyl groups, for example,

[0256] R2 C 4 -C 18 Alkyl or an R 2-1 Substituted C 1 -C 5 Alkyl groups, for example,

[0257] R 2-1 For-NR b R b or hydroxyl;

[0258] Each R b are independently hydrogen or C 1 -C 6 alkyl;

[0259] X is

[0260] R 3 is hydrogen;

[0261] Preferably, the weight average molecular weight of the compound as shown in Formula I is 1890-5330, preferably 2700-4100, for example, 2700, 3100, 3500 or 4100.

[0262] In one scheme, n is 8-11;

[0263] R is -(CH 2 )m-; said-(CH 2 )0 to 3 -CH in m- 2 - is optionally substituted with O, m is 4-11; for example,

[0264] R 1 C 8 -C 18 Alkyl groups, for example,

[0265] In a preferred embodiment, R 2 C 4 -C 18 Alkyl or an R 2-1 Substituted C 1 -C 5 Alkyl groups, for example,

[0266] R 2-1 For-NR b R b or hydroxyl;

[0267] Each Rb are independently hydrogen or C 1 -C 6 alkyl;

[0268] X is

[0269] R 3 is hydrogen;

[0270] Preferably, the weight average molecular weight of the compound as shown in Formula I is 1890-4500, preferably 2700-3500, for example, 2700, 3100 or 3500.

[0271] In one scheme, n is 8-10;

[0272] R is -(CH 2 )m-; said-(CH 2 )0 to 3 -CH in m- 2 - is optionally substituted with O, m is 4-11; for example,

[0273] R 1 C 10 -C 16 Alkyl groups, for example,

[0274] R 2 C 4 -C 16 Alkyl or an R 2-1 Substituted C 1 -C 5 Alkyl groups, for example,

[0275] R 2-1 For-NR b R b or hydroxyl;

[0276] Each R b are independently hydrogen or C 1 -C 6 alkyl;

[0277] X is

[0278] R 3 is hydrogen;

[0279] Preferably, the weight average molecular weight of the compound as shown in Formula I is 2450-5330, preferably, 3500-4100, for example, 3500 or 4100.

[0280] In one scheme, n is 8-10;

[0281] R is -(CH 2 )m-; said-(CH 2 )0 to 3 -CH in m- 2 - is optionally substituted with O, m is 4-11; for example,

[0282] R 1 C 10 -C 16 Alkyl groups, for example,

[0283] R 2 C 4 -C 16 Alkyl or an R 2-1 Substituted C 1 -C 5 Alkyl groups, for example,

[0284] R 2-1 is hydroxyl group;

[0285] X is

[0286] R 3 is hydrogen;

[0287] Preferably, the weight average molecular weight of the compound as shown in Formula I is 2450-5330, preferably, 3500-4100, for example, 3500 or 4100.

[0288] In one scheme, n is 8-10;

[0289] R is -(CH 2 )m-; said-(CH 2 )0 to 3 -CH in m- 2 - is optionally substituted with O, m is 4-11; for example,

[0290] R 1 C 10 -C 16 Alkyl groups, for example,

[0291] R 2 C 4 -C 16 Alkyl or an R 2-1 Substituted C 1 -C 5 Alkyl groups, for example,

[0292] R 2-1 For-NR b R b or hydroxyl;

[0293] Each R b Independently for C 1 -C 6 alkyl;

[0294] X is

[0295] R 3 is hydrogen;

[0296] Preferably, the weight average molecular weight of the compound as shown in Formula I is 2450-5330, preferably 3500-4100, for example, 3500 or 4100.

[0297] In one scheme, n is 8-9;

[0298] R is -(CH 2 )m-; m is 4-6; for example,

[0299] R 1 C 14 -C 16 Alkyl groups, for example,

[0300] R 2 C 4 -C 16 Alkyl or an R 2-1 Substituted C 1 -C 5 Alkyl groups, for example,

[0301]

[0302] R 2-1 For-NR b R b or hydroxyl;

[0303] Each R b are independently hydrogen or C 1 -C 6 alkyl;

[0304] X is

[0305] R 3 is hydrogen;

[0306] Preferably, the weight average molecular weight of the compound as shown in Formula I is 2450-4550, for example, 3500.

[0307] In one scheme, n is 8-9;

[0308] R is -(CH 2 )m-; m is 4-6; for example, R 1 C 14 -C 16 Alkyl groups, for example, R 2 C 4 -C 16 Alkyl or an R 2-1 Substituted C 1 -C 5 Alkyl groups, for example,

[0309]

[0310] R 2-1 For-NR b R b or hydroxyl;

[0311] Each R b are independently hydrogen or C 1 -C 6 alkyl;

[0312] X is

[0313] R 3 is hydrogen;

[0314] Preferably, the weight average molecular weight of the compound as shown in Formula I is 2450-4550, for example, 3500.

[0315] In one scheme, n is 8-9;

[0316] R is -(CH 2 )m-; m is 4-6; for example, R 1 C 14 -C 16 Alkyl groups, for example, R 2 C 4 -C 16 Alkyl or an R 2-1 Substituted C 1 -C 5 Alkyl groups, for example,

[0317]

[0318] R 2-1 is hydroxyl group;

[0319] Rb is hydrogen;

[0320] X is

[0321] R 3 is hydrogen;

[0322] Preferably, the weight average molecular weight of the compound as shown in Formula I is 2450-4550, for example, 3500.

[0323] In one scheme, n is 9-10;

[0324] R is -(CH 2 )m-; said-(CH 2 )0 to 3 -CH in m- 2 - is optionally substituted with O, m is 4-11; for example,

[0325]

[0326] R 1 C 8 -C 12 Alkyl groups, for example, R 2 C 4 -C 10 Alkyl or an R 2-1 Substituted C 1 -C 5 Alkyl groups, for example,

[0327] R 2-1 For-NR b R b or hydroxyl;

[0328] Each R b are independently hydrogen or C 1 -C 6 Alkyl; X is R 3 is hydrogen;

[0329] Preferably, the weight average molecular weight of the compound as shown in Formula I is 2870-5330, for example, 4100.

[0330] In one scheme, n is 9-10;

[0331] R is -(CH 2 )m-; said-(CH 2 )0 to 3 -CH in m- 2 - is optionally substituted with O, m is 4-11; for example,

[0332]

[0333] R 1 C 8 -C 12 Alkyl groups, for example, R 2 C 4 -C 10 Alkyl groups, for example, X is

[0334] R 3 is hydrogen;

[0335] Preferably, the weight average molecular weight of the compound as shown in Formula I is 2870-5330, for example, 4100.

[0336] In a preferred embodiment, the compound as shown in Formula I or a pharmaceutically acceptable salt thereof is any one of the compounds in the following table:

[0337]

[0338]

[0339]

[0340]

[0341]

[0342]

[0343]

[0344]

[0345] In a preferred embodiment, the compound as shown in Formula I or a pharmaceutically acceptable salt thereof is any compound as shown in Table 1:

[0346] Table 1

[0347]

[0348]

[0349]

[0350]

[0351]

[0352]

[0353]

[0354]

[0355]

[0356] The present invention also provides a blank polymer-lipid nanoparticle, which includes an ionizable polymer PBAE, wherein the ionizable polymer PBAE is the compound shown in Formula I as described above or a pharmaceutically acceptable salt thereof.

[0357] In a preferred embodiment, the blank polymer-lipid nanoparticles further include a diluent, which can be an organic phase and an aqueous phase.

[0358] In a preferred embodiment, in the diluent, the organic phase can be selected from ethanol, acetone, tetrahydrofuran, acetonitrile, etc. that are miscible with water, preferably ethanol; the aqueous phase can be selected from sodium citrate buffer with pH=3 or sodium acetate buffer with pH=5, preferably sodium acetate.

[0359] In a preferred embodiment, in the diluent, the volume ratio of the organic phase to the aqueous phase may be 1:1-1:3, preferably 1:2 and 1:3.

[0360] In a preferred embodiment, the blank polymer-lipid nanoparticles further include auxiliary phospholipids.

[0361] In a preferred embodiment, the auxiliary phospholipid may be DSPC, DOPE, DOPC, DSPE and derivatives thereof, preferably DOPE.

[0362] In a preferred embodiment, the blank polymer-lipid nanoparticles further include sterol.

[0363] In a preferred embodiment, the sterol may be cholesterol and its derivatives, preferably cholesterol.

[0364] In a preferred embodiment, the blank polymer-lipid nanoparticles further include lipids that inhibit particle aggregation. In a preferred embodiment, the lipids that inhibit particle aggregation can be polyethylene glycol and its derivatives, preferably DMG-PEG.

[0365] In a preferred embodiment, the molar ratio of the ionizable polymer PBAE to the auxiliary phospholipid is 1:0.03-2.5, preferably 1:1 or 1:0.48.

[0366] In a preferred embodiment, the molar ratio of the ionizable polymer PBAE to sterol is 1:0.67-6.5, preferably 1:2 or 1:2.40.

[0367] In a preferred embodiment, the molar ratio of the ionizable polymer PBAE to the particle aggregation inhibiting lipid is 1:0.01-1, preferably 1:0.20 or 1:0.12.

[0368] In the present invention, the molar ratio means the percentage of a substance in the mass of the ionizable polymer PBAE substance, and the sum of the molar contents of each component in the blank polymer-lipid nanoparticles does not exceed 100 mol%.

[0369] In a preferred embodiment, the blank polymer-lipid nanoparticles are composed of the ionizable polymer PBAE and common lipids, wherein the common esters are auxiliary phospholipids, sterols and lipids that inhibit particle aggregation.

[0370] In a preferred embodiment, the blank polymer-lipid nanoparticles are composed of the ionizable polymer PBAE, DOPE, cholesterol and DMG-PEG, and the molar ratios of the ionizable polymer PBAE, DOPE, cholesterol and DMG-PEG are 23.8:23.8:47.6:4.8 and 25:12:60:3.

[0371] The present invention also provides a nucleic acid drug polymer-lipid nanoparticle, which comprises a nucleic acid drug and the aforementioned blank polymer-lipid nanoparticle.

[0372] In a preferred embodiment, the nucleic acid drug may be a conventional nucleic acid molecule in the art, and the nucleic acid molecule may be mRNA, saRNA, cirRNA, miRNA, shRNA, siRNA, dsDNA, pDNA, preferably mRNA.

[0373] In a preferred embodiment, the N / P ratio of the ionizable polymer PBAE and the nucleic acid molecule may be 5:1-50:1, preferably 25:1, 12.5:1 or 21:1.

[0374] In a preferred embodiment, the nucleic acid drug polymer-lipid nanoparticle further comprises a diluent, which can be an organic phase and an aqueous phase.

[0375] In a preferred embodiment, in the diluent, the organic phase can be selected from ethanol, acetone, tetrahydrofuran, acetonitrile, etc. that are miscible with water, preferably ethanol; the aqueous phase can be selected from sodium citrate buffer with pH=3 or sodium acetate buffer with pH=5, preferably sodium acetate.

[0376] In a preferred embodiment, in the diluent, the volume ratio of the organic phase to the aqueous phase may be 1:1-1:3.

[0377] The present invention provides an application of an ionizable polymer PBAE in the preparation of a delivery system, wherein the ionizable polymer PBAE is a compound as shown in Formula I or a pharmaceutically acceptable salt thereof, and the delivery system is a system for delivering a therapeutic agent and / or a preventive agent to the lungs and / or liver; and the therapeutic agent and / or the preventive agent is a nucleic acid drug.

[0378] In a preferred embodiment, the delivery is targeted delivery.

[0379] In a preferred embodiment, the delivery system is the blank polymer-lipid nanoparticles mentioned above.

[0380] In a preferred embodiment, the ionizable polymer PBAE, blank polymer-lipid nanoparticles and nucleic acid drugs are as described above.

[0381] The present invention provides an application of an ionizable polymer PBAE as a pharmaceutical excipient, wherein the ionizable polymer PBAE is a compound as shown in Formula I or a pharmaceutically acceptable salt thereof, and the functions of the pharmaceutical excipient include nucleic acid encapsulation, lung or / and liver targeted delivery, and promoting effective cell uptake or lysosomal escape.

[0382] The present invention provides an application of a composition A in preparing a delivery system or preparing a drug for treating and / or preventing a disease, wherein the disease is a lung or / and liver-related disease, the composition nucleic acid drug polymer-lipid nanoparticle comprises an ionizable polymer PBAE, the ionizable polymer PBAE is a compound as shown in formula I or a pharmaceutically acceptable salt thereof, and the delivery system is as described above.

[0383] In a preferred embodiment, the composition A also includes one or more of auxiliary phospholipids, sterols, lipids that inhibit particle aggregation and / or nucleic acid drugs, and the auxiliary phospholipids, sterols, lipids that inhibit particle aggregation and / or nucleic acid drugs in the composition A are as described above.

[0384] In a preferred embodiment, in the composition A, the ionizable polymer PBAE forms blank polymer-lipid nanoparticles as described above with one or more of the auxiliary phospholipids, sterols, and lipids that inhibit particle aggregation.

[0385] In a preferred embodiment, in the composition A, the blank polymer-lipid nanoparticles and the nucleic acid drug form the nucleic acid drug polymer-lipid nanoparticles as described above.

[0386] In a preferred embodiment, in the composition A, the average particle size of the blank polymer-lipid nanoparticles of the composition may be 30-200 nm, and the surface potential may be -20-+20 mV.

[0387] In a preferred embodiment, in the composition A, the average particle size of the nucleic acid drug polymer-lipid nanoparticles in the composition can be 50-300 nm, and the surface potential can be -20-+20 mV.

[0388] In the present invention, the -(CH 2 )m- in -CH 2 - optionally independently substituted, with (CH 2 )m- in -CH 2 - are optionally independently replaced and have the same meaning; all represent -CH 2 - was replaced.

[0389] Unless otherwise specified, the terms used in the present invention have the following meanings:

[0390] The term "pharmaceutically acceptable" means relatively non-toxic, safe, and suitable for use by patients.

[0391] The term "pharmaceutically acceptable salt" refers to a salt obtained by reacting a compound with a pharmaceutically acceptable acid or base. When a compound contains a relatively acidic functional group, a base addition salt can be obtained by contacting the compound with a sufficient amount of a pharmaceutically acceptable base in a suitable inert solvent. Pharmaceutically acceptable base addition salts include, but are not limited to, sodium salts, potassium salts, calcium salts, aluminum salts, magnesium salts, bismuth salts, ammonium salts, and the like. When a compound contains a relatively basic functional group, an acid addition salt can be obtained by contacting the compound with a sufficient amount of a pharmaceutically acceptable acid in a suitable inert solvent. Pharmaceutically acceptable acid addition salts include, but are not limited to, hydrochlorides, sulfates, mesylate salts, and the like. For details, see Handbook of Pharmaceutical Salts: Properties, Selection, and Use (P. Heinrich Stahl, Camille G. Wermuth, 2011, 2nd Revised Edition).

[0392] In the structure fragment It means that the structural fragment is connected to the rest of the molecule through this site.

[0393] A "-" at the end of a group means that the group is attached to the rest of the molecule through that site.

[0394] The term "alkyl" refers to a group having a specified number of carbon atoms (e.g. 1 ~C 22 Alkyl, C 1 ~C 6 The invention relates to a saturated, linear or branched, monovalent hydrocarbon group. Examples thereof include, but are not limited to, ethyl, propyl, butyl, and the like.

[0395] The term "alkenyl" refers to a linear or branched monovalent hydrocarbon radical (e.g., C 2 to C 22) of two to twenty-two carbon atoms having at least one site of unsaturation, i.e., a carbon-carbon sp2 double bond. 2 ~C 22 Examples of which include, but are not limited to: wait.

[0396] The term "alkynyl" refers to a straight or branched monovalent hydrocarbon radical of two to twenty-two carbon atoms having at least one site of unsaturation, ie, a carbon-carbon sp triple bond.

[0397] The term "cycloalkyl" refers to a monovalent hydrocarbon group which is monocyclic or polycyclic (eg, fused, spiro or bridged) in which each carbon atom is saturated. 1 ~C 6 The cycloalkyl group may specifically be a 3-, 4-, 5- or 6-membered cycloalkyl group, including cyclopropyl, cyclobutyl, cyclopentyl and the like.

[0398] The term "cycloalkylene" refers to a divalent group which is attached to the rest of the molecule by two single bonds, and the rest is the same as the definition of the term "cycloalkyl".

[0399] The term "heteroalkyl" refers to a group in which at least one carbon atom in an alkyl group is replaced by a heteroatom selected from N, O and S. 1 -C 4 The heteroalkyl group may specifically be a 1-, 2-, 3- or 4-membered heteroalkyl group.

[0400] The term "heterocycloalkyl" refers to a group in which at least one carbon atom in a cycloalkyl group is replaced by a heteroatom selected from N, O and S. The 3-7 membered heterocycloalkyl group may specifically be a 3-, 4-, 5-, 6- or 7-membered heterocycloalkyl group.

[0401] The term "aryl" refers to an aromatic carbocyclic ring in which each ring is aromatic, C 6 ~C 12 The aromatic ring may specifically be a benzene ring or a naphthalene ring.

[0402] The term "arylene" refers to a divalent group which is attached to the rest of the molecule by two single bonds, and the rest is the same as the definition of the term "aryl".

[0403] On the basis of being in accordance with the common sense in the art, the above-mentioned preferred conditions can be arbitrarily combined to obtain the preferred embodiments of the present invention.

[0404] The reagents and raw materials used in the present invention are commercially available.

[0405] The positive improvement effect of the present invention is that the poly-β-amino lipid compound of the present invention has at least any of the following advantages over the existing PBAE: (1) higher effectiveness, (2) higher targeting and (3) higher safety. BRIEF DESCRIPTION OF THE DRAWINGS

[0406] Figure 1 is the body weight change within 7 days after administration of 1C16X in Example 33;

[0407] Figure 2 The body weight change within 7 days after administration of 3C10X in Example 33. DETAILED DESCRIPTION

[0408] The present invention is further described below by way of examples, but the present invention is not limited to the scope of the examples. The experimental methods in the following examples without specifying specific conditions are carried out according to conventional methods and conditions, or selected according to the product specifications.

[0409] The present invention uses the following general reaction formula to synthesize the aforementioned compound of formula I for poly-β-amino ester. The naming rule of the compound of formula I is as follows: the compound is named according to the abbreviated number of the synthesized main chain B, side chain S and end cap E monomer structure number (for example: B is selected as the B1 main chain, S is selected as the C12 amine side chain and E is selected as the NH2 end capping group. The product obtained by the polymerization reaction is named "1C12NH2").

[0410] Reaction Formula I

[0411]

[0412] The main chain B and the side chain S are added in an equivalent ratio of 1.1:1, and reacted at 65-90°C overnight without solvent, and the reaction was monitored by nuclear magnetic hydrogen spectrum. After reaching the target degree of polymerization, the heating was stopped, B and S were dissolved in THF at a concentration of 200 mg / mL, and 10 times the equivalent of end capping E was added, and the reaction was allowed to proceed at room temperature for 24 hours. After the end capping reaction was completed, the polymer was precipitated by ether or ethanol precipitation method, and washed twice to obtain the product.

[0413] Where B is

[0414]

[0415]

[0416] Where S is

[0417]

[0418]

[0419] Where E is

[0420]

[0421] The blank polymer-lipid nanoparticles disclosed in the present invention contain ionizable polymers and common lipids, and are characterized by having an average particle size of 30-200 nm and a surface potential of -20-+20 mV. The ionizable polymer is PBAE, and the common lipids are divided into three types: auxiliary phospholipids, sterols, and lipids that inhibit particle aggregation.

[0422] The four components of blank polymer-lipid nanoparticles include:

[0423] a) Ionizable polymer PBAE

[0424] b) Auxiliary phospholipids: DSPC, DOPE, DOPC, DSPE and their derivatives, preferably DOPE

[0425] c) Sterols: cholesterol and its derivatives, preferably cholesterol

[0426] d) Lipids that inhibit particle aggregation: polyethylene glycol and its derivatives, preferably DMG-PEG

[0427] The molar ratio of ionizable polymer PBAE: auxiliary phospholipid: sterol: particle aggregation inhibiting lipid is: x:y:(100-xyz):z; wherein the range of x is 10-60 mol%, the range of y is 2-20 mol%, and the range of z is 0.5-10 mol%.

[0428] The blank polymer-lipid nanoparticle preparation method disclosed in the present invention is an organic solvent injection method, and a microfluidics method is selected for the amplified preparation.

[0429] The process of preparing blank polymer-lipid nanoparticles by organic solvent injection method is as follows:

[0430] Weigh appropriate amounts of ionizable polymer PBAE, auxiliary phospholipids, cholesterol and lipid-polyethylene glycol, and dilute them in an organic solvent (the organic solvent can be ethanol, acetone, tetrahydrofuran, acetonitrile, etc. that are miscible with water, preferably ethanol) according to the set molar ratio of the four components. Rapidly inject the organic phase into the aqueous phase (the aqueous phase can be sodium citrate buffer at pH = 3, sodium acetate buffer at pH = 5, preferably sodium acetate) at a volume ratio of 1:1-1:3, mix well, and after the sample is incubated on ice for 2-10 minutes, the components assemble to form blank nanoparticles.

[0431] The nucleic acid drug polymer-lipid nanoparticle disclosed by the invention contains nucleic acid drug and blank polymer-lipid nanoparticle, and is characterized by having an average particle diameter of 50-300nm and a surface potential of -20-+20mV.

[0432] The composition of nucleic acid drug polymer-lipid nanoparticles includes:

[0433] (1) Nucleic acid molecules. Including but not limited to mRNA, saRNA, cirRNA, miRNA, shRNA, siRNA, dsDNA, pDNA, preferably mRNA;

[0434] (2) Lipid composition.

[0435] The four components include:

[0436] a) Ionizable polymer PBAE

[0437] b) Auxiliary phospholipids: DSPC, DOPE, DOPC, DSPE and their derivatives, preferably DOPE

[0438] c) Sterols: cholesterol and its derivatives, preferably cholesterol

[0439] d) Lipids that inhibit particle aggregation: polyethylene glycol and its derivatives, preferably DMG-PEG

[0440] The molar ratio of ionizable polymer PBAE: auxiliary phospholipid: sterol: particle aggregation inhibiting lipid is: x:y:(100-xyz):z, wherein x ranges from 10-60 mol%, y ranges from 2-25 mol%, and z ranges from 0.5-10 mol%. The N / P ratio of ionizable polymer and nucleic acid molecule is 5:1-50:1.

[0441] The process of preparing mRNA polymer-lipid nanoparticles using the organic solvent injection method is as follows:

[0442] Weigh an appropriate amount of ionizable polymer PBAE, auxiliary phospholipids, cholesterol and lipid-polyethylene glycol, and dilute them in an organic solvent (the organic solvent can be ethanol, acetone, tetrahydrofuran, acetonitrile, etc. that are miscible with water, preferably ethanol) according to the set molar ratio of the four components. The mRNA is diluted in an aqueous solution (the aqueous phase can be sodium citrate buffer at pH = 3, sodium acetate buffer at pH = 5, preferably sodium acetate), wherein the nitrogen-phosphorus ratio of the ionizable polymer to the mRNA is 5:1-50:1. The organic phase is quickly injected into the aqueous solution with mRNA at a volume ratio of 1:1-1:3, mixed evenly, and after the sample is placed on ice for incubation for 2-10 minutes, the components are assembled to form mRNA polymer-lipid nanoparticles. If the nanoparticles are characterized in vitro, they can be used directly. For in vivo screening, they need to be dialyzed in 2000 times the volume of PBS at 4°C for 2 hours to remove the organic solvent and form the final nanoparticles.

[0443] Example 1

[0444] Polymer PBAE:

[0445]

[0446] According to the above reaction formula, the reaction was carried out with propane-1,3-diyl diacrylate (202.6 mg, 1.1 mmol) and octylamine (129.2 mg, 1.0 mmol) as raw materials. After stirring at 65°C without solvent for about 30 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n (polymerization degree n is the average degree of polymerization, the subsequent embodiments have the same meaning n = 8-10 (actual n = 9.55)), the heating was stopped, and the weight average molecular weight of the polymer was calculated to be about 2900, and the molar weight was 0.1144 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and octylamine (147.8 mg, 1.144 mmol) was added to cap the end, and the reaction was carried out at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product. The product was finally verified by nuclear magnetic resonance hydrogen spectrum, product: 165 mg, 45.67%. 1 H NMR(500MHz,Chloroform-d)δ4.15(t,J=6.4Hz,38H),2.82(t,J=6.94Hz,38H),2.52(t,J=7.3Hz,38H),2.4 5(t,J=6.96Hz,21H),1.99–1.94(m,19H),1.47–1.37(m,21H),1.31–1.23(m,106H),0.88(t,J=7.0Hz,31H). Mn=3894.

[0447] Example 2

[0448]

[0449] According to the above reaction formula, the reaction was carried out with propane-1,3-diyl diacrylate (202.6 mg, 1.1 mmol) and octylamine (129.2 mg, 1.0 mmol) as raw materials. After stirring at 65°C without solvent for about 30 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n=8-10 (actual n=9.55), the heating was stopped. The weight average molecular weight of the polymer was calculated to be about 2900, and the molar weight was 0.1144 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of dodecyl primary amine (212.0 mg, 1.144 mmol) was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product. The product was finally verified by nuclear magnetic resonance hydrogen spectrum, product: 170 mg, 45.43%.

[0450] Example 3

[0451]

[0452] According to the above reaction formula, the reaction was carried out with propane-1,3-diyl diacrylate (202.6 mg, 1.1 mmol) and octylamine (129.2 mg, 1.0 mmol) as raw materials. After stirring at 65°C without solvent for about 30 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n=8-10 (actual n=9.55), the heating was stopped. The weight average molecular weight of the polymer was calculated to be about 2900, and the molar weight was 0.1144 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of hexadecylamine (276.2 mg, 1.144 mmol) was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product. Product: 168 mg, 43.41%.

[0453] Example 4

[0454]

[0455] According to the above reaction formula, the reaction was carried out with propane-1,3-diyl diacrylate (202.6 mg, 1.1 mmol) and dodecyl primary amine (185.3 mg, 1.0 mmol) as raw materials. After stirring at 65°C without solvent for about 30 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n=8-10 (actual n=9), the heating was stopped. The weight average molecular weight of the polymer was calculated to be about 3100, and the molar weight was 0.1251 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of octylamine (161.6 mg, 1.251 mmol) was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product. Product: 176 mg, 41.88%.

[0456] Example 5

[0457]

[0458] According to the above reaction formula, the reaction was carried out with propane-1,3-diyl diacrylate (202.6 mg, 1.1 mmol) and dodecyl primary Amine (1853 mg 10 mmol) was used as the starting material and stirred at 65°C without solvent for about 30 hours. The hydrogen NMR Spectral monitoring reactionProcess, after the reaction reaches the target degree of polymerization n = 8-10 (actual n = 9), stop heating, calculate the weight average molecular weight of the polymer is about 3100, the molar weight is 0.1251mmol. The polymer is dissolved in THF at a concentration of 200mg / mL, and 10 times the molar amount of dodecyl primary amine (231.8mg, 1.251mmol) is added for end-capping, and reacted at room temperature for 24 hours. After the reaction is completed, the polymer is precipitated with 10 times the volume of ethanol and washed twice to obtain the product. Product: 185mg, 42.60%.

[0459] Example 6

[0460]

[0461] According to the above reaction formula, the reaction was carried out with propane-1,3-diyl diacrylate (202.6 mg, 1.1 mmol) and dodecyl primary amine (185.3 mg, 1.0 mmol) as raw materials. After stirring at 65°C without solvent for about 30 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n=8-10 (actual n=9), the heating was stopped. The weight average molecular weight of the polymer was calculated to be about 3100, and the molar weight was 0.1251 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of hexadecylamine (302.03 mg, 1.251 mmol) was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product. Product: 208 mg, 46.40%.

[0462] Example 7

[0463]

[0464] According to the above reaction formula, the reaction was carried out with propane-1,3-diyl diacrylate (202.6 mg, 1.1 mmol) and hexadecylamine (241.4 mg, 1.0 mmol) as raw materials. After stirring at 65°C without solvent for about 30 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n=8-10 (actual n=10.12), the heating was stopped. The weight average molecular weight of the polymer was calculated to be about 4200, and the molar weight was 0.1057 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of octylamine (136.6 mg, 1.057 mmol) was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product. Product: 232 mg, 49.22%.

[0465] Example 8

[0466]

[0467] According to the above reaction formula, the reaction was carried out with propane-1,3-diyl diacrylate (202.6 mg, 1.1 mmol) and hexadecylamine (241.4 mg, 1.0 mmol) as raw materials. After stirring at 65°C without solvent for about 30 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n=8-10 (actual n=10.12), the heating was stopped. The weight average molecular weight of the polymer was calculated to be about 4200, and the molar weight was 0.1057 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of dodecyl primary amine (195.9 mg, 1.057 mmol) was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product. Product: 238 mg, 49.26%.

[0468] Example 9

[0469]

[0470] According to the above reaction formula, the reaction was carried out with propane-1,3-diyl diacrylate (202.6 mg, 1.1 mmol) and hexadecylamine (241.4 mg, 1.0 mmol) as raw materials. After stirring at 65°C without solvent for about 30 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n=8-10 (actual n=10.12), the heating was stopped. The weight average molecular weight of the polymer was calculated to be about 4200, and the molar weight was 0.1057 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of hexadecylamine (255.2 mg, 1.057 mmol) was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product. Product: 249 mg, 50.30%. 1 H NMR(500MHz,Chloroform-d)δ4.14(t,J=6.4Hz,40H),2.82(t,J=6.95Hz,4.03+36.09H),2.52(t,J=6.95Hz,4.14+35.79H) ,2.46(t,J=6.85Hz,4.06+18.94H),1.99–1.94(m,20H),1.43–1.37(m,22H),1.31–1.23(m,289H),0.88(t,J=6.9Hz,33H).

[0471] Example 10

[0472]

[0473] According to the above reaction formula, 1,5-pentanediol diacrylate (233.5 mg, 1.1 mmol) and octylamine (129.2 mg, 1.0 mmol) were used as raw materials. After stirring at 65°C without solvent for about 30 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n = 8-10 (actual n = 8.1), the heating was stopped. The weight average molecular weight of the polymer was calculated to be about 2600, and the molar weight was 0.1395 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and octylamine (180.2 mg, 1.395 mmol) was added to cap the end, and the reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product. Product: 142 mg, 35.61%. 1 H NMR(500MHz,Chloroform-d)δ4.10–4.05(m,32H),2.83(t,J=6.9Hz,3.21+29.87H),2.52(t,J=7.2Hz,3.28+29.63H) ,2.47(t,J=7Hz,3.29+15.48H),1.69–1.63(m,32H),1.44–1.38(m,34H),1.31–1.23(m,91H),0.88(t,J=6.9Hz,27H). Mn:3987.

[0474] Embodiment 11

[0475]

[0476] According to the above reaction formula, 1,5-pentanediol diacrylate (233.5 mg, 1.1 mmol) and octylamine (129.2 mg, 1.0 mmol) were used as raw materials. After stirring at 65°C without solvent for about 30 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n = 8-10 (actual n = 8.1), the heating was stopped. The weight average molecular weight of the polymer was calculated to be about 2600, and the molar weight was 0.1395 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of dodecyl primary amine (258.5.0 mg, 1.395 mmol) was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product. Product: 170 mg, 41.02%.

[0477] Example 12

[0478]

[0479] According to the above reaction formula, 1,5-pentanediol diacrylate (233.5 mg, 1.1 mmol) and octylamine (129.2 mg, 1.0 mmol) were used as raw materials. After stirring at 65°C without solvent for about 30 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n = 8-10 (actual n = 8.1), the heating was stopped. The weight average molecular weight of the polymer was calculated to be about 2600, and the molar weight was 0.1395 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of hexadecylamine (336.8 mg, 1.395 mmol) was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product. Product: 178 mg, 41.39%.

[0480] Embodiment 13

[0481]

[0482] According to the above reaction formula, 1,5-pentanediol diacrylate (233.5 mg, 1.1 mmol) and dodecyl primary amine (185.3 mg, 1.0 mmol) were used as raw materials. After stirring at 65°C without solvent for about 30 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n=8-10 (actual n=8), the heating was stopped. The weight average molecular weight of the polymer was calculated to be about 3000, and the molar weight was 0.1396 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of octylamine (180.4 mg, 1.396 mmol) was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product. Product: 197 mg, 43.31%.

[0483] Embodiment 14

[0484]

[0485] According to the above reaction formula, 1,5-pentanediol diacrylate (233.5 mg, 1.1 mmol) and dodecyl primary amine (185.3 mg, 1.0 mmol) were used as raw materials. After stirring at 65°C without solvent for about 30 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n=8-10 (actual n=8), the heating was stopped. The weight average molecular weight of the polymer was calculated to be about 3000, and the molar weight was 0.1396 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of dodecyl primary amine (258.7 mg, 1.396 mmol) was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product. Product: 184 mg, 39.10%.

[0486] Embodiment 15

[0487]

[0488] According to the above reaction formula, 1,5-pentanediol diacrylate (233.5 mg, 1.1 mmol) and dodecyl primary amine (185.3 mg, 1.0 mmol) were used as raw materials. After stirring at 65°C without solvent for about 30 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n=8-10 (actual n=8), the heating was stopped. The weight average molecular weight of the polymer was calculated to be about 3000, and the molar weight was 0.1396 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of hexadecylamine (337.0 mg, 1.396 mmol) was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product. Product: 192 mg, 39.49%.

[0489] Example 16

[0490]

[0491] According to the above reaction formula, 1,5-pentanediol diacrylate (233.5 mg, 1.1 mmol) and hexadecylamine (241.4 mg, 1.0 mmol) were used as raw materials. After stirring at 65°C without solvent for about 30 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n=8-10 (actual n=8), the heating was stopped. The weight average molecular weight of the polymer was calculated to be about 3400, and the molar weight was 0.1397 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of octylamine (180.5 mg, 1.397 mmol) was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product. Product: 210 mg, 41.10%.

[0492] Embodiment 17

[0493]

[0494] According to the above reaction formula, 1,5-pentanediol diacrylate (233.5 mg, 1.1 mmol) and hexadecylamine (241.4 mg, 1.0 mmol) were used as raw materials. After stirring at 65°C without solvent for about 30 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n=8-10 (actual n=8), the heating was stopped. The weight average molecular weight of the polymer was calculated to be about 3400, and the molar weight was 0.1397 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of dodecyl primary amine (258.9 mg, 1.397 mmol) was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product. Product: 199 mg, 37.78%.

[0495] Embodiment 18

[0496]

[0497] According to the above reaction formula, 1,5-pentanediol diacrylate (233.5 mg, 1.1 mmol) and hexadecylamine (241.4 mg, 1.0 mmol) were used as raw materials. After stirring at 65°C without solvent for about 30 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n = 8-10 (actual n = 8.19), the heating was stopped. The weight average molecular weight of the polymer was calculated to be about 3400, and the molar weight was 0.1397 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of hexadecylamine (377.3 mg, 1.397 mmol) was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product. Product: 212 mg, 39.09%. 1 H NMR(500MHz,Chloroform-d)δ4.10-4.05(m,33H),2.83(t,J=7.0Hz,3.5+29.67H),2.52(t,J=7.3Hz,3.78+29.23H),2 .46(t,J=7.1Hz,3.92+15.05H),1.69–1.63(m,33H),1.45–1.37(m,35H),1.31–1.23(m,239H),0.88(t,J=6.9Hz,28H).

[0498] Embodiment 19

[0499]

[0500] According to the above reaction formula, 1,4-butanediol diacrylate (218.0 mg, 1.1 mmol) and octylamine (129.2 mg, 1.0 mmol) were used as raw materials. After stirring at 65°C without solvent for about 30 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n = 8-10 (actual n = 8.63), the heating was stopped. The weight average molecular weight of the polymer was calculated to be about 2700, and the molar weight was 0.1286 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and octylamine (147.8 mg, 1.286 mmol) was added to cap the end. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product. Product: 159 mg, 41.79%. 1 H NMR(500MHz,Chloroform-d)δ4.11–4.07(m,35H),2.83(t,J=7.00Hz,3.09+32.48H),2.53(t,J=7.2Hz,3.25+31.53H),2.47(t,J=7.3Hz,

[0501] 3.16+17.12H),1.71–1.69(m,35H),1.44–1.38(m,19H),1.31–1.22(m,96H),0.88(t,J=6.9Hz,29H). Mn:4138.

[0502] Embodiment 20

[0503]

[0504] According to the above reaction formula, 1,4-butanediol diacrylate (218.0 mg, 1.1 mmol) and octylamine (129.2 mg, 1.0 mmol) were used as raw materials. After stirring at 65°C without solvent for about 30 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n = 8-10 (actual n = 8.63), the heating was stopped. The weight average molecular weight of the polymer was calculated to be about 2700, and the molar weight was 0.1286 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of dodecyl primary amine (238.3 mg, 1.286 mmol) was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product. Product: 158 mg, 40.01%.

[0505] Embodiment 21

[0506]

[0507] According to the above reaction formula, 1,4-butanediol diacrylate (218.0 mg, 1.1 mmol) and octylamine (129.2 mg, 1.0 mmol) were used as raw materials. After stirring at 65°C without solvent for about 30 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n = 8-10 (actual n = 8.63), the heating was stopped. The weight average molecular weight of the polymer was calculated to be about 2700, and the molar weight was 0.1286 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of hexadecylamine (310.48 mg, 1.286 mmol) was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product. Product: 177 mg, 43.24%.

[0508] Embodiment 22

[0509]

[0510] According to the above reaction formula, 1,4-butanediol diacrylate (218.0 mg, 1.1 mmol) and dodecyl primary amine (185.3 mg, 1.0 mmol) were used as raw materials. After stirring at 65°C without solvent for about 30 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n = 8-10 (actual n = 8.63), the heating was stopped. The weight average molecular weight of the polymer was calculated to be about 3100, and the molar weight was 0.07623 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of octylamine (98.5 mg, 0.7623 mmol) was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product. Product: 189 mg, 44.68%.

[0511] Embodiment 23

[0512]

[0513] According to the above reaction formula, 1,4-butanediol diacrylate (218.0 mg, 1.1 mmol) and dodecyl primary amine (185.3 mg, 1.0 mmol) were used as raw materials. After stirring at 65°C without solvent for about 30 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n = 8-10 (actual n = 8.63), heating was stopped. The calculated weight-average molecular weight of the polymer was about 3100 and the molar weight was 0.07623 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of dodecyl primary amine was added. Amine (141.3 mg, 0.7623 mmol) was used for end-capping and reacted at room temperature for 24 hours. After the polymerization, the polymer was precipitated with 10 times the volume of ethanol. The mixture was washed twice to obtain the product. Product: 187 mg, 43.33%. 1 H NMR(500MHz,Chloroform-d)δ4.12–4.06(m,35H),2.83(t,J=7.00Hz,3.08+31.8H),2.52(t,J=7.3Hz,3.05+30.56H),2 .46(t,J=7.05Hz,3.07+16.81H),1.71–1.69(m,35H),1.44–1.38(m,19H),1.31–1.23(m,174H),0.88(t,J=6.9Hz,29H).

[0514] Embodiment 24

[0515]

[0516] According to the above reaction formula, 1,4-butanediol diacrylate (218.0 mg, 1.1 mmol) and dodecyl primary amine (185.3 mg, 1.0 mmol) were used as raw materials. After stirring at 65°C without solvent for about 30 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n = 8-10 (actual n = 8.63), the heating was stopped. The weight average molecular weight of the polymer was calculated to be about 3100, and the molar weight was 0.07623 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of hexadecylamine (184.0 mg, 0.7623 mmol) was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product. Product: 185 mg, 42.04%.

[0517] Embodiment 25

[0518]

[0519] According to the above reaction formula, 1,4-butanediol diacrylate (218.0 mg, 1.1 mmol) and hexadecylamine (241.4 mg, 1.0 mmol) were used as raw materials. After stirring at 65°C without solvent for about 30 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n = 8-10 (actual n = 8.49), the heating was stopped. The weight average molecular weight of the polymer was calculated to be about 3500, and the molar weight was 0.1313 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of octylamine (169.6 mg, 1.313 mmol) was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product. Product: 193 mg, 39.12%.

[0520] Embodiment 26

[0521]

[0522] According to the above reaction formula, 1,4-butanediol diacrylate (218.0 mg, 1.1 mmol) and hexadecylamine (241.4 mg, 1.0 mmol) were used as raw materials. After stirring at 65°C without solvent for about 30 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n = 8-10 (actual n = 8.49), the heating was stopped. The weight average molecular weight of the polymer was calculated to be about 3500, and the molar weight was 0.1313 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of dodecyl primary amine (243.3.0 mg, 1.313 mmol) was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product. Product: 200 mg, 40.55%.

[0523] Embodiment 27

[0524]

[0525] According to the above reaction formula, 1,4-butanediol diacrylate (218.0 mg, 1.1 mmol) and hexadecylamine (241.4 mg, 1.0 mmol) were used as raw materials. After stirring at 65°C without solvent for about 30 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n = 8-10 (actual n = 8.49), the heating was stopped. The weight average molecular weight of the polymer was calculated to be about 3500, and the molar weight was 0.1313 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of hexadecylamine (317.0 mg, 1.313 mmol) was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product. Product: 222 mg, 42.46%. 1 H NMR(500MHz,Chloroform-d)δ4.12–4.07(m,34H),2.83(t,J=6.90Hz,4.29+28.95H),2.52(t,J=7.3Hz,4.56+28.14H),2.46 (t,J=7.0Hz,4.2+15.12H),1.71–1.69(m,34H),1.43–1.38(m,19H),1.31–1.23(m,246H),0.88(t,J=6.9Hz,28H).Mn:4032.

[0526] Embodiment 28

[0527]

[0528] According to the above reaction formula, tetraethylene glycol diacrylate (332.55 mg, 1.1 mmol) and decylamine (157.3 mg, 1.0 mmol) were used as raw materials. After stirring at 65°C without solvent for about 24 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n = 8-10 (actual n = 9.78), the heating was stopped. The weight average molecular weight of the polymer was calculated to be about 4100, and the molar weight was 0.1195 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 1,3-propylenediamine (88.6 mg, 1.195 mmol) was added to cap the end. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product. Product: 210 mg, 36.30%.

[0529] Embodiment 29

[0530]

[0531] According to the above reaction formula, tetraethylene glycol diacrylate (332.55 mg, 1.1 mmol) and decylamine (157.3 mg, 1.0 mmol) were used as raw materials. After stirring at 65°C without solvent for about 24 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n = 8-10 (actual n = 9.78), the heating was stopped. The weight average molecular weight of the polymer was calculated to be about 4100, and the molar weight was 0.1195 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of N-methyl-1,3-propylenediamine (105.3 mg, 1.195 mmol) was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product. Product: 239 mg, 40.16%.

[0532] Embodiment 30

[0533]

[0534] According to the above reaction formula, tetraethylene glycol diacrylate (332.55 mg, 1.1 mmol) and decylamine (157.3 mg, 1.0 mmol) were used as raw materials. After stirring at 65°C without solvent for about 24 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n = 8-10 (actual n = 9.78), the heating was stopped. The weight average molecular weight of the polymer was calculated to be about 4100, and the molar weight was 0.1195 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of 3-dimethylaminopropylamine (122.1 mg, 1.195 mmol) was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product. Product: 225 mg, 36.77%.

[0535] Embodiment 31

[0536]

[0537] According to the above reaction formula, tetraethylene glycol diacrylate (332.55 mg, 1.1 mmol) and decylamine (157.3 mg, 1.0 mmol) were used as raw materials. After stirring at 65°C without solvent for about 24 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n = 8-10 (actual n = 9.78), the heating was stopped. The weight average molecular weight of the polymer was calculated to be about 4100, and the molar weight was 0.1195 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of n-butylamine (87.4 mg, 1.195 mmol) was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product. Product: 253 mg, 43.83%.

[0538] Embodiment 32

[0539]

[0540] According to the above reaction formula, tetraethylene glycol diacrylate (332.55 mg, 1.1 mmol) and decylamine (157.3 mg, 1.0 mmol) were used as raw materials. After stirring at 65°C without solvent for about 24 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n = 8-10 (actual n = 9.78), the heating was stopped. The weight average molecular weight of the polymer was calculated to be about 4100, and the molar weight was 0.1195 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and decylamine (188.0 mg, 1.195 mmol) was added to cap the end, and the reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 volumes of ethanol and washed twice to obtain the product. Product: 295 mg, 43.52%.

[0541] Example 33 7C8C8 n=5.3

[0542]

[0543] According to the above reaction formula, the reaction was carried out with propane-1,3-diyl diacrylate (122.1 mg, 1.1 eq) and octylamine (78.0 mg, 1.0 eq) as raw materials. After stirring at 75°C without solvent for about 3 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n (the degree of polymerization n is the average degree of polymerization, and the subsequent embodiments have the same meaning n=5-6 (actual n=5.36)), the heating was stopped. The calculated weight average molecular weight of the polymer was about 1549.552, and the molar weight was 0.129 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and octylamine (94.4 mg, 1.29 mmol) with a 10-fold molar amount thereof was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10-fold volume of methanol and washed twice to obtain the product. 1 H NMR (500MHz, CDCl3) δ4.26-4.13(m,21H),2.82(t,J=7.5Hz,21H),2.53(t,J=7.5Hz,21H),2. 47(t,J=7.5Hz,12H),1.99–1.84(m,11H),1.43–1.23(m,73H),0.88(t,J=5Hz,19H).Mn:2957.

[0544] Embodiment 34

[0545] 7C8C8 n=14.05

[0546]

[0547] According to the above reaction formula, the reaction was carried out with propane-1,3-diyl diacrylate (122.1 mg, 1.1 eq) and octylamine (78.0 mg, 1.0 eq) as raw materials. After stirring at 75°C without solvent for about 40 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n (the degree of polymerization n is the average degree of polymerization, and the subsequent embodiments have the same meaning n = 14-15 (actual n = 14.05)), the heating was stopped, and the weight average molecular weight of the polymer was calculated to be about 4271.26, and the molar weight was 0.047 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and octylamine (60.5 mg, 0.47 mmol) with a 10-fold molar amount thereof was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10-fold volume of ethanol and washed twice to obtain the product. 1 HNMR (500MHz, CDCl3) δ4.18-4.13(m,56H),2.82(t,J=7.5Hz,56H),2.52(t,J=7.5Hz,56H),2.4 6(t,J=7.5Hz,30H),1.99–1.94(m,28H),1.43–1.23(m,180H),0.88(t,J=5.0Hz,45H).Mn:5661

[0548] Example 35 7C8C4 n=9.6

[0549]

[0550] According to the above reaction formula, the reaction was carried out with propane-1,3-diyl diacrylate (122.1 mg, 1.1 eq) and octylamine (78.0 mg, 1.0 eq) as raw materials. After stirring at 75°C without solvent for about 7.5 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n (the degree of polymerization n is the average degree of polymerization, and the subsequent embodiments have the same meaning n = 9-10 (actual n = 9.6)), the heating was stopped, and the calculated polymer weight average molecular weight was about 2890.048, and the molar weight was 0.069 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of butylamine (50.6 mg, 0.69 mmol) was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product. 1H NMR (500MHz, CDCl3) δ4.18-4.13(m,39H),2.82(t,J=7.5Hz,38H),2.53(t,J=7.5Hz,38H),2.4 6(t,J=7.5Hz,21H),1.99–1.94(m,19H),1.43–1.22(m,112H),0.9(t,J=7.5Hz,31H).Mn:5321

[0551] Example 36 7C8C12 n=9.6

[0552]

[0553] According to the above reaction formula, the reaction was carried out with propane-1,3-diyl diacrylate (122.1 mg, 1.1 eq) and octylamine (78.0 mg, 1.0 eq) as raw materials. After stirring at 75°C without solvent for about 7.5 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n (the degree of polymerization n is the average degree of polymerization, and the subsequent embodiments have the same meaning n = 9-10 (actual n = 9.6)), the heating was stopped, and the calculated polymer weight average molecular weight was about 2890.048, and the molar weight was 0.069 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of dodecyl primary amine (128.27 mg, 0.69 mmol) was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product.

[0554] Example 37 7C8C16 n=9.6

[0555]

[0556] According to the above reaction formula, the reaction was carried out with propane-1,3-diyl diacrylate (122.1 mg, 1.1 eq) and octylamine (78.0 mg, 1.0 eq) as raw materials. After stirring at 75°C without solvent for about 7.5 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n (the degree of polymerization n is the average degree of polymerization, and the subsequent embodiments have the same meaning n = 9-10 (actual n = 9.6)), the heating was stopped, and the calculated polymer weight average molecular weight was about 2890.048, and the molar weight was 0.069 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of hexadecyl primary amine (167.1 mg, 0.69 mmol) was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product.

[0557] Example 38 7C4C8 n=9.34

[0558]

[0559] According to the above reaction formula, the reaction was carried out with propane-1,3-diyl diacrylate (221.62 mg, 1.1 eq) and butylamine (80.0 mg, 1.0 eq) as raw materials. After stirring at 75°C without solvent for about 7.5 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n (the degree of polymerization n is the average degree of polymerization, and the subsequent embodiments have the same meaning n = 9-10 (actual n = 9.34)), the heating was stopped, and the weight average molecular weight of the polymer was calculated to be about 2328.79, and the molar weight was 0.129 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of octylamine (166.6 mg, 1.29 mmol) was added for end-capping, and the reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product.

[0560] Example 39 7C12C8 n=9.96

[0561]

[0562] According to the above reaction formula, the reaction was carried out with propane-1,3-diyl diacrylate (163.96 mg, 1.1 eq) and dodecyl primary amine (150 mg, 1.0 eq) as raw materials. After stirring at 75°C without solvent for about 43 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n (the degree of polymerization n is the average degree of polymerization, and the subsequent embodiments have the same meaning n = 9-10 (actual n = 9.96)), the heating was stopped, and the calculated polymer weight average molecular weight was about 3492.92, and the molar weight was 0.090 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of octylamine (116.23 mg, 0.9 mmol) was added for end-capping, and the reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product. 1 H NMR (500MHz, CDCl3) δ4.18-4.13(m,40H),2.82(t,J=7.5Hz,39H),2.52(t,J=7.5Hz,39H),2.4 6(t,J=7.5Hz,21H),1.99–1.94(m,20H),1.43-1.22(m,213H),0.88(t,J=5.0Hz,33H).Mn:3794

[0563] Example 40 7C16C8 n=10.44

[0564]

[0565] According to the above reaction formula, the reaction was carried out with propane-1,3-diyl diacrylate (125.86 mg, 1.1 eq) and hexadecyl primary amine (150 mg, 1.0 eq) as raw materials. After stirring at 90°C without solvent for about 32 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n (the degree of polymerization n is the average degree of polymerization, and the subsequent embodiments have the same meaning n = 10-11 (actual n = 10.44)), the heating was stopped, and the weight average molecular weight of the polymer was calculated to be about 4199.384, and the molar weight was 0.066 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of octylamine (84.8 mg, 0.66 mmol) was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product. 1 H NMR (500MHz, CDCl3) δ4.18–4.13(m,42H),2.82(t,J=7.5Hz,42H),2.52(t,J=7.5Hz,42H),2.4 6(t,J=7.5Hz,23H),1.99–1.94(m,21H),1.43-1.23(m,296H),0.88(t,J=7.5Hz,35H).Mn:3855

[0566] Example 41 7C8G12 n=9.52

[0567]

[0568] According to the above reaction formula, the reaction was carried out with propane-1,3-diyl diacrylate (122.1 mg, 1.1 eq) and octylamine (78 mg, 1.0 eq) as raw materials. After stirring at 75°C without solvent for about 7.5 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n (degree of polymerization n is the average degree of polymerization, the subsequent embodiments have the same meaning n = 9-10 (actual n = 9.52)), the heating was stopped, and the calculated polymer weight average molecular weight was about 2852.464, and the molar weight was 0.07 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of N-dodecylmethylamine (139.8 mg, 0.7 mmol) was added for end-capping, and the reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product.

[0569] Example 42 7C8G14 n=9.52

[0570]

[0571] According to the above reaction formula, the reaction was carried out with propane-1,3-diyl diacrylate (122.1 mg, 1.1 eq) and octylamine (78 mg, 1.0 eq) as raw materials. After stirring at 75°C without solvent for about 7.5 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n (degree of polymerization n is the average degree of polymerization, the subsequent embodiments have the same meaning n = 9-10 (actual n = 9.52)), the heating was stopped, and the weight average molecular weight of the polymer was calculated to be about 2852.464, and the molar weight was 0.07 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of N-methylallylamine (49.8 mg, 0.7 mmol) was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product.

[0572] Example 43 7C8G15 n=9.52

[0573]

[0574] According to the above reaction formula, the reaction was carried out with propane-1,3-diyl diacrylate (122.1 mg, 1.1 eq) and octylamine (78 mg, 1.0 eq) as raw materials. After stirring at 75°C without solvent for about 7.5 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n (the degree of polymerization n is the average degree of polymerization, and the subsequent embodiments have the same meaning n = 9-10 (actual n = 9.52)), the heating was stopped, and the calculated polymer weight average molecular weight was about 2852.464, and the molar weight was 0.07 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of N-methylpropargylamine (48.4 mg, 0.7 mmol) was added for end-capping, and the reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product.

[0575] Example 44 7C8G16 n=9.52

[0576]

[0577] According to the above reaction formula, the reaction was carried out with propane-1,3-diyl diacrylate (122.1 mg, 1.1 eq) and octylamine (78 mg, 1.0 eq) as raw materials. After stirring at 75°C without solvent for about 7.5 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n (the degree of polymerization n is the average degree of polymerization, and the subsequent embodiments have the same meaning n = 9-10 (actual n = 9.52)), the heating was stopped, and the weight average molecular weight of the polymer was calculated to be about 2852.464, and the molar weight was 0.07 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of N,N,N'-trimethylethylenediamine (71.5 mg, 0.7 mmol) was added for end-capping, and the reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product.

[0578] Example 45 7C8G17 n=9.52

[0579]

[0580] According to the above reaction formula, the reaction was carried out with propane-1,3-diyl diacrylate (122.1 mg, 1.1 eq) and octylamine (78 mg, 1.0 eq) as raw materials. After stirring at 75°C without solvent for about 7.5 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n (degree of polymerization n is the average degree of polymerization, the subsequent embodiments have the same meaning n = 9-10 (actual n = 9.52)), the heating was stopped, and the weight average molecular weight of the polymer was calculated to be about 2852.464, and the molar weight was 0.07 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of N-methylphenylethylamine (94.6 mg, 0.7 mmol) was added for end-capping, and the reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product. 1 HNMR (500MHz, CDCl3) δ7.30-7.27(m,6H),7.20–7.18(m,4H),4.18-4.13(m,38H),2.82(t,J=7.5Hz,40H),2.53(t,J=7.5Hz,40H), 2.54–2.47(m,4H),2.39(t,J=7.5Hz,18H),2.31(s,4H),1.99–1.94(m,19H),1.43–1.25(m,108H),0.88(t,J=5.0Hz,26H).Mn:3761

[0581] Example 46 7C8G18 n=9.52

[0582]

[0583] According to the above reaction formula, the reaction was carried out with propane-1,3-diyl diacrylate (122.1 mg, 1.1 eq) and octylamine (78 mg, 1.0 eq) as raw materials. After stirring at 75°C without solvent for about 7.5 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n (the degree of polymerization n is the average degree of polymerization, and the subsequent embodiments have the same meaning n = 9-10 (actual n = 9.52)), the heating was stopped, and the weight average molecular weight of the polymer was calculated to be about 2852.464, and the molar weight was 0.07 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of N-methyl-4-bromobenzylamine (140.05 mg, 0.7 mmol) was added for end-capping, and the reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product. 1 H NMR (500MHz, CDCl3) δ7.43 (d, J = 5Hz, 4H), 7.17 (d, J = 10Hz, 4H), 4.17-4.12 (m, 38H), 2.82 (t, J = 7.5Hz, 38H), 2.54 (t ,J=7.5Hz,27H),2.52(t,J=7.5Hz,38H),1.99–1.95(m,20H),1.43–1.25(m,112H),0.88(t,J=5.0Hz,26H).Mn:3322

[0584] Example 47 7C8G19 n=9.52

[0585]

[0586] According to the above reaction formula, the reaction was carried out with propane-1,3-diyl diacrylate (122.1 mg, 1.1 eq) and octylamine (78 mg, 1.0 eq) as raw materials. After stirring at 75°C without solvent for about 7.5 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n (the degree of polymerization n is the average degree of polymerization, and the subsequent embodiments have the same meaning n = 9-10 (actual n = 9.52)), the heating was stopped, and the weight average molecular weight of the polymer was calculated to be about 2852.464, and the molar weight was 0.07 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 4-n-butylamino-1-butanol (101.67 mg, 0.7 mmol) with a 10-fold molar amount thereof was added for end-capping, and the reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10-fold volume of ethanol and washed twice to obtain the product. 1H NMR (500MHz, CDCl3) δ4.18-4.13(m,38H),2.82(t,J=7.5Hz,38H),2.57(t,J=7.5Hz,25H),2.5 2(t,J=7.5Hz,40H),1.99–1.94(m,19H),1.43–1.25(m,118H),0.9(t,J=5.0Hz,31H).Mn:4436

[0587] Example 48 7C8G20 n=9.52

[0588]

[0589] According to the above reaction formula, the reaction was carried out with propane-1,3-diyl diacrylate (122.1 mg, 1.1 eq) and octylamine (78 mg, 1.0 eq) as raw materials. After stirring at 75°C without solvent for about 7.5 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n (the degree of polymerization n is the average degree of polymerization, and the subsequent embodiments have the same meaning n = 9-10 (actual n = 9.52)), the heating was stopped, and the weight average molecular weight of the polymer was calculated to be about 2852.464, and the molar weight was 0.07 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of allylcyclohexylamine (97.46 mg, 0.7 mmol) was added for end-capping, and the reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product. 1 HNMR (500MHz, CDCl3) δ4.26–4.13(m,38H),2.83(t,J=7.5Hz,38H),2.52(t,J=7.5Hz,38H),2.4 6(t,J=7.5Hz,20H),2.06–1.94(m,19H),1.43–1.25(m,118H),0.88(t,J=5.0Hz,27H).Mn:5235

[0590] Example 49 7C8G21 n=9.52

[0591]

[0592] According to the above reaction formula, the reaction was carried out with propane-1,3-diyl diacrylate (122.1 mg, 1.1 eq) and octylamine (78 mg, 1.0 eq) as raw materials. After stirring at 75°C without solvent for about 7.5 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n (the degree of polymerization n is the average degree of polymerization, and the subsequent embodiments have the same meaning n = 9-10 (actual n = 9.52)), the heating was stopped, and the weight average molecular weight of the polymer was calculated to be about 2852.464, and the molar weight was 0.07 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of N-ethyltetrahydro-2H-pyran-4-amine (90.44 mg, 0.7 mmol) was added for end-capping, and the reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product. 1 H NMR (500MHz, CDCl3) δ4.26–4.13(m,39H),2.83(t,J=7.5Hz,38H),2.55(t,J=7.5Hz,38H),2.4 8(t,J=7.5Hz,21H),2.06–1.94(m,19H),1.43–1.25(m,120H),0.88(t,J=5.0Hz,30H).Mn:5452

[0593] Example 50 7C8G22 n=9.52

[0594]

[0595] According to the above reaction formula, the reaction was carried out with propane-1,3-diyl diacrylate (122.1 mg, 1.1 eq) and octylamine (78 mg, 1.0 eq) as raw materials. After stirring at 75°C without solvent for about 7.5 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n (degree of polymerization n is the average degree of polymerization, the subsequent embodiments have the same meaning n = 9-10 (actual n = 9.52)), the heating was stopped, and the weight average molecular weight of the polymer was calculated to be about 2852.464, and the molar weight was 0.07 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 1-methyl-4-(methylamino)piperidine (89.75 mg, 0.7 mmol) was added for end-capping, and the reaction was carried out at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product.

[0596] Example 51 7C8G23 n=9.52

[0597]

[0598] According to the above reaction formula, the reaction was carried out with propane-1,3-diyl diacrylate (122.1 mg, 1.1 eq) and octylamine (78 mg, 1.0 eq) as raw materials. After stirring at 75°C without solvent for about 7.5 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n (degree of polymerization n is the average degree of polymerization, the subsequent embodiments have the same meaning n = 9-10 (actual n = 9.52)), the heating was stopped, and the calculated polymer weight average molecular weight was about 2852.464, and the molar weight was 0.07 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of octadecyl mercaptan (200.59 mg, 0.7 mmol) was added for end-capping, and the reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product.

[0599] Example 52 7C8G24 n=9.52

[0600]

[0601] According to the above reaction formula, the reaction was carried out with propane-1,3-diyl diacrylate (122.1 mg, 1.1 eq) and octylamine (78 mg, 1.0 eq) as raw materials. After stirring at 75°C without solvent for about 7.5 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n (the degree of polymerization n is the average degree of polymerization, and the subsequent embodiments have the same meaning n = 9-10 (actual n = 9.52)), the heating was stopped, and the weight average molecular weight of the polymer was calculated to be about 2852.464, and the molar weight was 0.07 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and cyclohexanethiol (81.35 mg, 0.7 mmol) of 10 times the molar amount thereof was added for end-capping, and the reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product.

[0602] Example 53 7C8G25 n=9.52

[0603]

[0604] According to the above reaction formula, the reaction was carried out with propane-1,3-diyl diacrylate (122.1 mg, 1.1 eq) and octylamine (78 mg, 1.0 eq) as raw materials. After stirring at 75°C without solvent for about 7.5 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n (the degree of polymerization n is the average degree of polymerization, and the subsequent embodiments have the same meaning n = 9-10 (actual n = 9.52)), the heating was stopped, and the calculated polymer weight average molecular weight was about 2852.464, and the molar weight was 0.07 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and furan-2-methyl mercaptan (79.9 mg, 0.7 mmol) was added in a 10-fold molar amount for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10-fold volume of ethanol and washed twice to obtain the product.

[0605] Example 54 7G2G2 n=9.67

[0606]

[0607] According to the above reaction formula, the reaction was carried out with propane-1,3-diyl diacrylate (200.8 mg, 1.1 eq) and oleylamine (264.4 mg, 1.0 eq) as raw materials. After stirring at 90°C without solvent for about 27 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n (the degree of polymerization n is the average degree of polymerization, and the subsequent embodiments have the same meaning n = 9-10 (actual n = 9.67)), the heating was stopped. The calculated weight average molecular weight of the polymer was about 4097.4579, and the molar weight was 0.11 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and oleylamine (294.2 mg, 1.1 mmol) of 10 times the molar amount thereof was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product. 1 HNMR (500MHz, CDCl3) δ5.39–5.31(m,18H),4.18–4.13(m,39H),2.82(t,J=7.5Hz,39H),2.52(t,J=7.5Hz ,39H),2.46(t,J=7.5Hz,22H),1.98-1.94(m,22H),1.49–1.23(m,299H),0.88(t,J=5.0Hz,33H).Mn:4297

[0608] Example 55 7G3G3 n=8.45

[0609]

[0610] According to the above reaction formula, the reaction was carried out with propane-1,3-diyl diacrylate (199.5 mg, 1.1 eq) and propargylamine (54.2 mg, 1.0 eq) as raw materials. After stirring at 75°C without solvent for about 60 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n (the degree of polymerization n is the average degree of polymerization, and the subsequent embodiments have the same meaning n = 8-9 (actual n = 8.45)), the heating was stopped, and the calculated polymer weight average molecular weight was about 1965.524, and the molar weight was 0.13 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of propargylamine (71.6 mg, 1.3 mmol) was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product.

[0611] Example 56 7G4G4 n=10.86

[0612]

[0613] According to the above reaction formula, the reaction was carried out with propane-1,3-diyl diacrylate (99.8 mg, 1.1 eq) and propyne-pentaethylene glycol-amine (136.3 mg, 1.0 eq) as raw materials. After stirring at 90°C without solvent for about 25 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n (the degree of polymerization n is the average degree of polymerization, and the subsequent embodiments have the same meaning n=10-11 (actual n=10.86)), the heating was stopped. The calculated weight average molecular weight of the polymer was about 4711.9892, and the molar weight was 0.05 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of propyne-pentaethylene glycol-amine (137.9 mg, 0.5 mmol) was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product.

[0614] Example 57 7G5G5 n=9.0

[0615]

[0616] According to the above reaction formula, the reaction was carried out with propane-1,3-diyl diacrylate (200.3 mg, 1.1 eq) and 2-amino-5-diethylaminopentane (156.5 mg, 1.0 eq) as raw materials. After stirring at 75°C without solvent for about 50 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n (the degree of polymerization n is the average degree of polymerization, and the subsequent embodiments have the same meaning n = 9-10 (actual n = 9.0)), the heating was stopped, and the calculated polymer weight average molecular weight was about 2922.08, and the molar weight was 0.12 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 2-amino-5-diethylaminopentane (193.27 mg, 1.2 mmol) with a 10-fold molar amount thereof was added for end-capping, and the reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10-fold volume of ethanol and washed twice to obtain the product.

[0617] Example 58 7G6G6 n=9.58

[0618]

[0619] According to the above reaction formula, the reaction was carried out with propane-1,3-diyl diacrylate (199.9 mg, 1.1 eq) and N-(3-aminopropyl)-N-methylaniline (163.2 mg, 1.0 eq) as raw materials. After stirring at 75° C. without solvent for about 25 hours and at 90° C. for 1.5 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n (the degree of polymerization n is the average degree of polymerization, and the subsequent embodiments have the same meaning n=9-10 (actual n=9.58)), the heating was stopped, and the calculated weight average molecular weight of the polymer was about 3173.69, and the molar weight was 0.11 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of N-(3-aminopropyl)-N-methylaniline (187.9 mg, 1.1 mmol) was added for end-capping. The reaction was allowed to react at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product.

[0620] Example 59 7G7G7 n=10.04

[0621]

[0622] According to the above reaction formula, the reaction was carried out with propane-1,3-diyl diacrylate (200 mg, 1.1 eq) and N-(3-aminopropyl) diethanolamine (159.7 mg, 1.0 eq) as raw materials. After stirring at 75°C without solvent for about 4 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n (the degree of polymerization n is the average degree of polymerization, and the subsequent embodiments have the same meaning n=10-11 (actual n=10.04)), the heating was stopped. The calculated weight average molecular weight of the polymer was about 3313.81, and the molar weight was 0.11 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of N-(3-aminopropyl) diethanolamine (176.1 mg, 1.1 mmol) was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product.

[0623] Example 60 7G8G8 n=10.32

[0624]

[0625] According to the above reaction formula, the reaction was carried out with propane-1,3-diyl diacrylate (200.5 mg, 1.1 eq) and 6-amino-1-hexanol (115.6 mg, 1.0 eq) as raw materials. After stirring at 75°C without solvent for about 7.5 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n (the degree of polymerization n is the average degree of polymerization, and the subsequent embodiments have the same meaning n=10-11 (actual n=10.32)), the heating was stopped, and the weight average molecular weight of the polymer was calculated to be about 2991.17, and the molar weight was 0.11 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 6-amino-1-hexanol (123.6 mg, 1.1 mmol) with a 10-fold molar amount thereof was added for end-capping, and the reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10-fold volume of ethanol and washed twice to obtain the product.

[0626] Example 61 7G10G10 n=8.27

[0627]

[0628] According to the above reaction formula, the reaction was carried out with propane-1,3-diyl diacrylate (200.3 mg, 1.1 eq) and cyclohexylmethylamine (111.8 mg, 1.0 eq) as raw materials. After stirring at 90°C without solvent for about 30 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n (the degree of polymerization n is the average degree of polymerization, and the subsequent embodiments have the same meaning n=8-9 (actual n=8.27)), the heating was stopped, and the calculated polymer weight average molecular weight was about 2344.6513, and the molar weight was 0.13 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and cyclohexylmethylamine (150.5 mg, 1.3 mmol) with a 10-fold molar amount thereof was added for end-capping, and the reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10-fold volume of ethanol and washed twice to obtain the product.

[0629] Example 62 7G11G11 n=9.11

[0630]

[0631] According to the above reaction formula, the reaction was carried out with propane-1,3-diyl diacrylate (204.6 mg, 1.1 eq) and 4-phenylbutylamine (150.7 mg, 1.0 eq) as raw materials. After stirring at 75°C without solvent for about 30 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n (the degree of polymerization n is the average degree of polymerization, and the subsequent embodiments have the same meaning n = 9-10 (actual n = 9.11)), the heating was stopped, and the weight average molecular weight of the polymer was calculated to be about 2886.25, and the molar weight was 0.12 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 4-phenylbutylamine (183.7 mg, 1.2 mmol) with a 10-fold molar amount thereof was added for end-capping, and the reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10-fold volume of ethanol and washed twice to obtain the product.

[0632] Example 63B29C8C8 n=11.1

[0633]

[0634] According to the above reaction formula, 1,6-di(acryloyloxy)-2,2,3,3,4,4,5,5-octafluorohexane (157.65 mg, 1.1 eq) and octylamine (50 mg, 1.0 eq) were used as raw materials. After stirring at 90°C without solvent for about 9 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n (the degree of polymerization n is the average degree of polymerization, and the subsequent embodiments have the same meaning n=11-12 (actual n=11.1)), the heating was stopped. The calculated weight average molecular weight of the polymer was about 5413.524, and the molar weight was 0.04 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and octylamine (49.5 mg, 0.4 mmol) with a 10-fold molar amount thereof was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10-fold volume of ethanol and washed twice to obtain the product.

[0635] Example 64B31C8C8 n=11.33

[0636]

[0637] The reaction was carried out according to the above reaction formula, with α-(1-oxo-2-propenyl)-ω-[(1-oxo-2-propenyl)oxy]-poly[oxy(methyl-1,2-ethylene)] (298.1 mg, 1.1 eq) and octylamine (50 mg, 1.0 eq) as raw materials. After stirring at 90° C. without solvent for about 5.5 hours, the reaction progress was monitored by hydrogen nuclear magnetic resonance spectroscopy. After the reaction reached the target degree of polymerization n (the degree of polymerization n is the average degree of polymerization, and the subsequent embodiments have the same meaning of n=11-12 (actual n=11.33)), the heating was stopped, and the calculated weight average molecular weight of the polymer was about 9265.1195, and the molar weight was 0.04 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of octylamine (51.66 mg, 0.4 mmol) was added for end-capping. The reaction was allowed to react at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product.

[0638] Example 65B33C8C8 n=11.78

[0639]

[0640] According to the above reaction formula, the reaction was carried out with polyethylene glycol diacrylate (244.87 mg, 1.1 eq) and octylamine (50 mg, 1.0 eq) as raw materials. After stirring at 90°C without solvent for about 22 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n (the degree of polymerization n is the average degree of polymerization, and the subsequent embodiments have the same meaning n = 11-12 (actual n = 11.78)), the heating was stopped, and the weight average molecular weight of the polymer was calculated to be about 8165.737, and the molar weight was 0.04 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and octylamine (51.66 mg, 0.4 mmol) with a 10-fold molar amount thereof was added for end-capping, and the reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10-fold volume of ethanol and washed twice to obtain the product.

[0641] Embodiment 66

[0642] B34C8C8 n=9.18

[0643]

[0644] According to the above reaction formula, 9,9-bis[4-(2-acryloyloxyethoxy)phenyl]fluorene (232.78 mg, 1.1 eq) and octylamine (50 mg, 1.0 eq) were used as raw materials. After stirring at 90°C without solvent for about 4.5 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n (the degree of polymerization n is the average degree of polymerization, and the subsequent embodiments have the same meaning n=9-10 (actual n=9.18)), the heating was stopped. The calculated weight average molecular weight of the polymer was about 6194.2968, and the molar weight was 0.04 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and octylamine (51.66 mg, 0.4 mmol) with a 10-fold molar amount thereof was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10-fold volume of ethanol and washed twice to obtain the product.

[0645] Embodiment 67

[0646] B35C8C8 n=11.55

[0647]

[0648] According to the above reaction formula, the reaction was carried out with ethylene glycol diacrylate (72.45 mg, 1.1 eq) and octylamine (50 mg, 1.0 eq) as raw materials. After stirring at 75°C without solvent for about 7 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n (the degree of polymerization n is the average degree of polymerization, and the subsequent embodiments have the same meaning n = 11-12 (actual n = 11.55)), the heating was stopped, and the weight average molecular weight of the polymer was about 3588.05, and the molar weight was 0.034 mmol. The polymer was dissolved in THF at a concentration of 200 mg / mL, and octylamine (45 mg, 0.34 mmol) with a 10-fold molar amount thereof was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10-fold volume of ethanol and washed twice to obtain the product.

[0649] Embodiment 68

[0650] 3C8N n=10.62

[0651]

[0652] According to the above reaction formula, tetraethylene glycol diacrylate (302.32 mg, 1.1 eq) and octylamine (117.4 mg, 1.0 eq) were used as raw materials. After stirring at 75°C without solvent for about 7 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n (the degree of polymerization n is the average degree of polymerization, and the subsequent embodiments have the same meaning n = 10-11 (actual n = 10.62)), the heating was stopped. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of N, N-dimethyl-1, 3-diaminopropane (96.5 mg, 0.95 mmol) was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product. 1 H NMR (500MHz, CDCl3) δ4.41–4.08(m,42H),3.71–3.63(m,125H),2.88(td,J=6.5,2.7Hz,2H),2.77(t,J=7.3Hz,39H),2.71–2.50(m,7H),2.50–2.42( m,38H),2.42–2.35(m,19H),2.31(td,J=7.3,2.1Hz,2H),2.22(s,6H),1.4 0(p,J=7.6Hz,20H),1.33–1.18(m,122H),0.88(t,J=7.0Hz,31H).Mn=4489

[0653] Embodiment 69

[0654] 3C12N n=8.95

[0655]

[0656] According to the above reaction formula, tetraethylene glycol diacrylate (302.32 mg, 1.1 eq) and dodecyl primary amine (168.5 mg, 1.0 eq) were used as raw materials. After stirring at 75°C without solvent for about 9 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n (the degree of polymerization n is the average degree of polymerization, and the subsequent embodiments have the same meaning n = 8-9 (actual n = 8.95)), the heating was stopped. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of N, N-dimethyl-1, 3-diaminopropane (115 mg, 1.14 mmol) was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product. 1 H NMR (500MHz, CDCl3) δ4.28–4.18(m,35H),3.71–3.64(m,109H),2.88(td,J= 6.4,4.0Hz,2H),2.77(t,J=7.4Hz,34H),2.71–2.50(m,7H),2.47(t,J=7.3H z,34H),2.43–2.35(m,18H),2.31(td,J=7.0,2.1Hz,2H),2.26–2.15(m,5H) ,1.42–1.38(m,15H),1.33–1.18(m,194H),0.88(t,J=7.0Hz,26H).Mn=4907.

[0657] Embodiment 70

[0658] 3C16N n=9.00

[0659]

[0660] According to the above reaction formula, tetraethylene glycol diacrylate (302.32 mg, 1.1 eq) and hexadecylamine (219.5 mg, 1.0 eq) were used as raw materials. After stirring at 90°C without solvent for about 7 hours, the reaction progress was monitored by nuclear magnetic resonance hydrogen spectrum. After the reaction reached the target degree of polymerization n (the degree of polymerization n is the average degree of polymerization, and the subsequent embodiments have the same meaning n = 9-10 (actual n = 9.00)), the heating was stopped. The polymer was dissolved in THF at a concentration of 200 mg / mL, and 10 times the molar amount of N, N-dimethyl-1, 3-diaminopropane (82.5 mg, 0.82 mmol) was added for end-capping. The reaction was reacted at room temperature for 24 hours. After the reaction was completed, the polymer was precipitated with 10 times the volume of ethanol and washed twice to obtain the product. 1H NMR (500MHz, CDCl3) δ4.29–4.18(m,36H),3.71–3.64(m,113H),2.88(td,J =6.6,3.1Hz,3H),2.77(t,J=7.4Hz,34H),2.71–2.51(m,7H),2.47(t,J=7. 3Hz,34H),2.39(t,J=7.5Hz,17H),2.35–2.27(m,2H),2.22(s,6H),1.40(p ,J=7.3Hz,20H),1.25(t,J=3.6Hz,281H),0.88(t,J=7.0Hz,28H).Mn=4862

[0661] Embodiment 71

[0662] Preparation and Characterization of mRNA Polymer-Lipid Nanoparticles (PLNPs)

[0663] Preparation method:

[0664] Method 1: Weigh appropriate amounts of ionizable polymer PBAE, DOPE, cholesterol and DMG-PEG to prepare an ethanol solution, prepare an ethanol organic phase according to the molar ratio of PBAE: DOPE: cholesterol: DMG-PEG = 23.8: 23.8: 47.6: 4.8, and dilute mRNA in a sodium citrate solution at pH = 3 as the aqueous phase, where the nitrogen-phosphorus ratio of the ionizable polymer to mRNA is 25:1 for B1 and B3, and 12.5:1 for B2. Rapidly inject the organic phase into the aqueous phase solution with mRNA at a volume ratio of 1:2, mix evenly, and after the sample is incubated on ice for 5 minutes, the components assemble to form mRNA polymer-lipid nanoparticles. If the nanoparticles are to be characterized in vitro, they can be used directly. For in vivo screening, they need to be dialyzed in 2000 times the volume of PBS at 4°C for 2 hours to remove the organic solvent and form the final nanoparticles.

[0665] Method 2: Weigh appropriate amounts of ionizable polymer PBAE, DOPE, cholesterol and DMG-PEG to form an ethanol solution, prepare the ethanol organic phase according to the molar ratio of PBAE: DOPE: cholesterol: DMG-PEG = 25:12:60:3, and dilute mRNA in sodium acetate solution at pH = 5 as the aqueous phase, where the nitrogen-phosphorus ratio of the ionizable polymer to mRNA is 21:1. The organic phase is quickly injected into the aqueous phase solution with mRNA at a volume ratio of 1:3, mixed evenly, and after the sample is incubated on ice for 5 minutes, the components assemble to form mRNA polymer-lipid nanoparticles. If the nanoparticles are to be characterized in vitro, they can be used directly. For in vivo screening, they need to be dialyzed in 2000 times the volume of PBS at 4°C for 2 hours to remove the organic solvent and form the final nanoparticles.

[0666] The particle size, potential and polydispersity index (PDI) of the mRNA polymer-lipid nanoparticles prepared by method 1 are shown in Table 1

[0667] Table 1 Properties of mRNA polymer-lipid nanoparticles of the present invention

[0668]

[0669]

[0670]

[0671]

[0672]

[0673]

[0674] The above data show that the particle size of the mRNA polymer-lipid nanoparticles of the present invention is between 50-200 nm, which meets the particle size requirements of the nucleic acid delivery carrier; the polydispersity coefficient PDI is less than 0.2, indicating that the mRNA polymer-lipid nanoparticles prepared by the ethanol injection method are uniform in size and have strong consistency; the Zeta potential is between -10 and +10 mV, indicating that the prepared mRNA polymer-lipid nanoparticles can effectively encapsulate nucleic acids while shielding excessive potential to prevent binding to various proteins in the blood circulation and being rapidly cleared.

[0675] Embodiment 72

[0676] The polymer-lipid nanoparticles prepared by method 1 were used to mediate cell transfection of EGFP plasmid and green fluorescent protein mRNA (Suzhou Nearshore Protein Technology Co., Ltd., catalog number MR008).

[0677] Experimental methods: PLNPs were prepared by in vitro characterization of polymer-lipid nanoparticles. 150 ng / well of pEGFP (purchased from Addgene) or mEGFP (purchased from Suzhou Jinan Protein Technology Co., Ltd.) was used to transfect HEK293T (purchased from the Institute of Cell Biology, Chinese Academy of Sciences) in 96-well plates, and the fluorescence expression was observed 24 hours after transfection.

[0678] Table 2 Quantification of EGFP green fluorescence expression in HEK 293T cells transfected with pDNA polymer-lipid nanoparticles of the present invention

[0679]

[0680]

[0681] The above results show that most of the three main chain molecules show obvious green fluorescence signals, among which B2 has the highest expression efficiency, followed by B1, and B3 has the lowest. They all show stronger transfection effects under polar blocking groups, and the expression intensity also increases with the increase of hydrophobic side chain length, especially when transfecting mRNA. This rule is more obvious.

[0682] Table 3 Quantification of EGFP green fluorescence expression in HEK 293T cells transfected with polymer-lipid nanoparticles of the green fluorescent protein mRNA (Suzhou Jinan Protein Technology Co., Ltd., Catalog No. MR008)

[0683]

[0684]

[0685] The above results show that most of the six main chain molecules show obvious green fluorescence signals, among which B5, B7, B8 and B2 have higher expression efficiency, followed by B1 and B3. They all show stronger transfection effects under polar blocking groups, and the expression intensity also increases with the increase of hydrophobic side chain length, especially when transfecting mRNA. This rule is more obvious.

[0686] Embodiment 73

[0687] The polymer-lipid nanoparticles prepared by method 1 were used to mediate in vivo transfection of luciferase mRNA (Suzhou Nearshore Protein Technology Co., Ltd., catalog number MR009).

[0688] Experimental methods: PLNPs were prepared by the polymer-lipid nanoparticle method screened in vivo. The dialyzed nanoparticles were diluted to 0.02 mg / mL with PBS and stored on ice. Then, luciferase mRNA was injected into mice (ICR, 3 weeks, male, n=3) via the tail vein at a dose of 0.2 mg / kg. Six hours after administration, luciferase substrate solution (15 mg / mL dissolved in DPBS) was intraperitoneally injected at a dose of 10 μL / g of mouse body weight for in vivo imaging to detect bioluminescent signals. The effectiveness and targeting of various PBAEs were evaluated by the strength of in vivo bioluminescent signals and the expression distribution of various organs after dissection.

[0689] Table 4 Quantitative expression of mRNA polymer-lipid nanoparticles of the present invention in vivo

[0690]

[0691]

[0692] Table 4-1 Quantitative expression of mRNA polymer-lipid nanoparticles in various organs of the present invention

[0693]

[0694]

[0695]

[0696]

[0697]

[0698] The above experimental results show that all six main chain molecules show effective in vivo expression, among which B1, B5, B7, B8 and B35 have higher expression efficiency, followed by B3, and B2 has the lowest. In addition, the expression effect also shows a certain correlation with the side chain and the end-capping group: when the end-capping group is the same, the in vivo expression gradually increases with the increase of the side chain length; polymers with a carbon chain length of 8-16 are likely to have good in vivo expression, while the carbon chain length of 18 and less than 8 is the second best. When the main chain and side chain are the same, the in vivo expression shows partial enhancement as the polarity of the end-capping group decreases.

[0699] Embodiment 74

[0700] Hemolysis experiment of blank mRNA polymer-lipid nanoparticles with liver and lung specific targeting and prepared by method 1

[0701] Experimental method: Blood was collected from C57BL / 6 mice through the eye sockets and placed in a heparin-moistened EP tube. After centrifugation at 3500rpm and 4℃ for 10 minutes, the supernatant was discarded to obtain red blood cells. The red blood cells were then diluted to 5 times the volume of 10mM PBS (pH 7.4), washed 5 times, and finally resuspended in 5 times the volume of PBS. 15μL of the diluted red blood cell suspension was added to 135μL of PBS containing different concentrations of unloaded PLNPs or PLNPs loaded with mRNA (PBAE 100ug / mL, 200ug / mL and 400ug / mL). After incubation at 37℃ for 1 hour, the sample was centrifuged at 3500rpm for 5 minutes, 100μL of the supernatant was taken and placed in a 96-well plate, and the absorbance at 545nm was read by an enzyme reader. The degree of red blood cell hemolysis caused by PBAE is proportional to the absorbance. The percentage of red blood cell hemolysis is calculated using the following formula:

[0702]

[0703] Table 5 Evaluation of the hemolytic activity of blank and mRNA polymer-lipid nanoparticles of the present invention

[0704]

[0705]

[0706] The above experimental results show that when red blood cells are incubated with liver-targeted 1C16X PLNPs at different concentrations, regardless of whether they are loaded with nucleic acids, PBAE without terminal amino groups exhibits relatively weak red blood cell hemolysis (<10%), while PBAE with amino termini significantly increases the probability of red blood cell hemolysis. This contrast is more significant in lung-targeted 3C10X materials. 3C10X with terminal amino groups leads to a high hemolysis rate of 30%-60% at low concentrations of PBAE, while 3C10X without terminal amino groups has no obvious hemolysis events (<10%) even at high concentrations.

[0707] Embodiment 75

[0708] Cytotoxicity experiments of blank mRNA polymer-lipid nanoparticles prepared by method 1 for liver and lung specific targeting

[0709] Experimental methods: Different concentrations of empty PLNPs or PLNPs loaded with mRNA were prepared by the polymer-lipid nanoparticle method. The cell survival rate of HEK 293T cells incubated with empty PLNPs or PLNPs loaded with mRNA at low doses of 40ug / mL and high doses of 80ug / mL of PBAE for 24 hours was detected using the CCK-8 kit.

[0710] Table 6 Evaluation of cytotoxicity of blank and mRNA polymer-lipid nanoparticles transfected HEK 293T cells of the present invention

[0711]

[0712]

[0713] The above experimental results show that in the liver-targeted material 1C16X, PBAE without terminal amino groups had almost no detected cell growth inhibition, while PBAE with terminal amino groups had obvious cytotoxicity, and the toxicity increased in a dose-dependent manner. However, the lung-targeted 3C10X material did not produce significant differences in cytotoxicity related to end-capping, and the cell status was basically normal with or without nucleic acid encapsulation and high-dose PBAE.

[0714] Embodiment 76

[0715] In vivo tolerance test of blank polymer-lipid nanoparticles with liver and lung specific targeting

[0716] Experimental method: First, the highest tolerated dose of each PBAE structure was determined through preliminary experiments, and it was found that the mouse tolerated dose of the 1C16X series was higher than that of the 3C10X series. Based on this, three PBAE dose gradients of low, medium, and high were set to reflect the differences in the in vivo toxicity of empty PLNPs under different structures. After each type of PLNPs was injected into mice through the tail vein, the survival rate and weight changes of the mice were continuously observed and recorded within 7 days.

[0717] Table 7 In vivo tolerance dose determination of blank polymer-lipid nanoparticle 1C16X of the present invention

[0718]

[0719] Table 8 In vivo tolerance dose determination of blank polymer-lipid nanoparticle 3C10X of the present invention

[0720]

[0721]

[0722] The above experimental results show that the presence of terminal amino groups significantly increased the mortality rate of mice, whether it is the liver-targeted 1C16X series or the lung-targeted 3C10X series. Compared with PBAE without terminal amino groups, PBAE with terminal amino groups caused the death of mice at a lower dosage, and the mortality rate gradually increased with the increase of dosage. Even at the highest dosage set, mice of PBAE without terminal amino groups remained normal.

[0723] Embodiment 77

[0724] The weight changes of mice within 7 days after administration of blank polymer-lipid nanoparticles 1C16X and 3C10X of the present invention at different doses were recorded. The weight changes of surviving mice within 7 days after administration were recorded. Basically, most mice (except 3C10C10) lost weight on the first day after administration, among which PBAE with an amino group at the end had a greater weight loss, and then the weight gradually recovered. All mice were able to basically recover to their initial weight before administration within 7 days. The weight changes of 1C16X within 7 days after administration were as follows: Figure 1 , the body weight changes within 7 days after 3C10X administration were as follows Figure 2 .

Claims

1. A compound as shown in formula I or a pharmaceutically acceptable salt thereof, characterized in that: Wherein, n is 2-20; R is -(CH2)m- or is replaced by one or more R a Substituted -(CH2)m-, wherein 0 to 12 -CH2- in the -(CH2)m- are optionally independently replaced by O, S, -NR b -, Sub-C6-C 12 Aryl, C3-C6 cycloalkylene, 1 or more R c Substituted C6-C 12 Aryl and 9,9-diphenylfluorenyl are substituted, and m is 1-40; Each R a are independently hydroxyl, -NR b R b , C1-C6 alkyl, halogen or C1-C4 heteroalkyl; the heteroatom species in the C1-C4 heteroalkyl is selected from one or more of O, S and N, and the number of heteroatoms is 1, 2 or 3; Each R b are independently hydrogen, C1-C6 alkyl, C6-C 12 Aryl, 1 or more R c Substituted C6-C 12 Aryl or one or more R b1 Substituted C1-C6 alkyl; Each R c are independently hydroxy, nitro, cyano, C1-C6 alkyl, halogen or amino; Each R b1 are independently hydroxyl groups; R 1 C1-C 22 Alkyl, C2-C 22 Alkenyl, C2-C 22 Alkynyl, with one or more R 1-1 Substituted C1-C 22 Alkyl, with one or more R 1-2 Substituted C2-C 22 Alkenyl or one or more R 1-3 Substituted C2-C 22 Alkynyl; the C1-C 22 0 to 8 -CH2- in the alkyl group are optionally independently replaced by O or S; 22 0 to 8 -CH2- in the alkenyl group are optionally independently replaced by O or S; 22 0 to 8 -CH2- in the alkynyl group are optionally independently replaced by O or S; Each R 1-1 , R 1-2 and R 1-3 Independently -NR b R b , hydroxyl, C6-C 12 Aryl or C3-C6 cycloalkyl; R 2 C1-C 22 Alkyl, C2-C 22 Alkenyl, C2-C 22 Alkynyl, with one or more R 2-1 Substituted C1-C 22 Alkyl, with one or more R 2-2 Substituted C2-C 22 Alkenyl, one or more R 2-3 Substituted C2-C 22 Alkynyl, C3-C6 cycloalkyl, 1 or more R 2e Substituted C3-C6 cycloalkyl, "a 3-7 membered heterocycloalkyl having 1, 2 or 3 heteroatoms selected from N, O and S" or substituted by 1 or more R 2f The substituted "heteroatom is selected from 1, 2 or 3 of N, O and S, and the number of heteroatoms is 1, 2 or 3 3-membered heterocycloalkyl", the C2-C 22 0 to 8 -CH2- in the alkynyl group are optionally replaced by O or S; Each R 2-1 , R 2-2 and R 2-3 Independently -NR b R b , hydroxyl, C6-C 12 Aryl, one or more R 2d3 Substituted C6-C 12 Aryl, C3-C6 cycloalkyl, one or more R 2d3 Substituted C3-C6 cycloalkyl, "a 5-10 membered heteroaryl group having 1, 2 or 3 heteroatoms selected from N, O and S" or one or more R 2d3 Substituted "5-10 membered heteroaryl group having 1, 2 or 3 heteroatoms selected from N, O and S"; Each R 2d3 are independently C1-C6 alkyl, halogen or halogenated C1-C6 alkyl; Each R 2e and R 2f are independently halogen, C1-C6 alkyl or halogenated C1-C6 alkyl; X is R 3 is hydrogen, C1-C 22 Alkyl, C2-C 22 Alkenyl, C2-C 22 Alkynyl, with one or more R 3-1 Substituted C1-C 22 Alkyl, with one or more R 3-2 Substituted C2-C 22 Alkenyl, one or more R 3-3 Substituted C2-C 22 Alkynyl, C3-C6 cycloalkyl, C6-C 12 Aryl or "3-7 membered heterocycloalkyl group whose heteroatoms are selected from 1, 2 or 3 of N, O and S, and whose heteroatoms are 1, 2 or 3"; Each R 3-1 , R 3-2 and R 3-3 Independently -NR b R b , C3-C6 cycloalkyl or hydroxy.

2. The compound of formula I or a pharmaceutically acceptable salt thereof according to claim 1, characterized in that: Wherein, n is 2-20; R is -(CH2)m- or is replaced by one or more R a Substituted -(CH2)m-, wherein 0 to 10 -CH2- in the -(CH2)m- are optionally replaced by O, S, -NR b -, Sub-C6-C 12 Aryl, C3-C6 cycloalkylene and 1 or more R c Substituted C6-C 12 Aryl, m is 1-30; Each R a are independently hydroxyl, -NR b R b , C1-C6 alkyl, halogen or C1-C4 heteroalkyl; the heteroatom species in the C1-C4 heteroalkyl is selected from one or more of O, S and N, and the number of heteroatoms is 1, 2 or 3; Each R b are independently hydrogen, C1-C6 alkyl, C6-C 12 Aryl or 1 or more R c Substituted C6-C 12 Aryl; Each R c are independently hydroxy, nitro, cyano, C1-C6 alkyl, halogen or amino; R 1 C1-C 22 Alkyl, C2-C 22 Alkenyl, C2-C 22 Alkynyl, with one or more R 1-1 Substituted C1-C 22 Alkyl, with one or more R 1-2 Substituted C2-C 22 Alkenyl or one or more R 1-3 Substituted C2-C 22 Alkynyl; Each R 1-1 , R 1-2 and R 1-3 Independently -NR b R b or hydroxyl; R 2 C1-C 22 Alkyl, C2-C 22 Alkenyl, C2-C 22 Alkynyl, with one or more R 2-1 Substituted C1-C 22 Alkyl, with one or more R 2-2 Substituted C2-C 22 Alkenyl or one or more R 2-3 Substituted C2-C 22 Alkynyl; Each R 2-1 , R 2-2 and R 2-3 Independently -NR b R b or hydroxyl; X is R 3 is hydrogen, C1-C 22 Alkyl, C2-C 22 Alkenyl, C2-C 22 Alkynyl, with one or more R 3-1 Substituted C1-C 22 Alkyl, with one or more R 3-2 Substituted C2-C 22 Alkenyl, one or more R 3-3 Substituted C2-C 22 Alkynyl, C3-C6 cycloalkyl, C6-C 12 Aryl or a 3-7-membered heterocycloalkyl group optionally substituted by 1, 2 or 3 heteroatoms, wherein the heteroatoms are optionally one or more of N, O and S; the number of heteroatoms is 1, 2 or 3; Each R 3-1 , R 3-2 and R 3-3 Independently -NR b R b , C3-C6 cycloalkyl or hydroxy.

3. The compound of formula I or a pharmaceutically acceptable salt thereof according to claim 1 or 2, characterized in that: The compound as shown in formula I satisfies one or more of the following conditions: (1) In R, in the -(CH2)m-, m is 1-27, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 12, 14, 15, 23 or 27; (2) In R, the one or more R a In the substituted -(CH2)m-, the plurality is 2-8, for example, 2, 3, 4, 5, 6, 7 or 8; (3) In R, 0 to 10 -CH2- in the -(CH2)m- are optionally replaced by O, S, -NR b -, Sub-C6-C 12 Aryl and 1 or more R c Substituted C6-C 12 Aryl means that 1 to 6 -CH2- in the -(CH2)m- are optionally substituted by O, and m can be 5-27, for example (4) In R, 0 to 10 -CH2- in the -(CH2)m- are optionally replaced by O, S, -NR b -, Sub-C6-C 12 Aryl and 1 or more R c Substituted C6-C 12 Aryl means that 1 to 2 -CH2- in the -(CH2)m- are optionally substituted by S, and m can be 1-6, for example (5) In R, 0 to 10 -CH2- in the -(CH2)m- are optionally replaced by O, S, -NR b -, Sub-C6-C 12 Aryl and 1 or more R c Substituted C6-C 12 Aryl is 1 to 2 -CH2- in the -(CH2)m-, which are optionally replaced by C6-C 12 Aryl and / or 1 or more R c Substituted C6-C 12 Aryl substitution, m can be 1-6, for example (6) In R, 0 to 10 -CH2- in the -(CH2)m- are optionally replaced by O, S, -NR b -, Sub-C6-C 12 Aryl and 1 or more R c Substituted C6-C 12 The aryl group is 1 to 6 -CH2- in the -(CH2)m- group, which are optionally replaced by O and C6-C 12 Aryl and / or 1 or more R c Substituted C6-C 12 Aryl substitution, e.g. (7) In R, the sub-C6-C 12 The aromatic group is C6-C 10 an aryl group, for example, phenylene; (8)R a wherein the C1-C6 alkyl group is a C1-C4 alkyl group, for example, methyl, ethyl; (9)R a wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine; (10) Each R a In the C1-C4 heteroalkyl group, the heteroatom type is O, S or N, such as O; the number of heteroatoms can be 2; for example (11)R a wherein the C1-C4 heteroalkyl group is a C4 heteroalkyl group; (12)R b wherein the C1-C6 alkyl group is a C1-C4 alkyl group, for example, a methyl group; (13)R b In the C6-C 12 The aryl group is C6-C 10 an aryl group, for example, a phenyl group; (14)R c wherein the C1-C6 alkyl group is a C1-C4 alkyl group, for example, a methyl group; (15)R c wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine; (16)R 1 In the above, C1-C 22 The alkyl group is C2-C 20 The alkyl group is preferably a straight chain C2-C 20 The alkyl group, for example, (17)R 1 In the C2-C 22 Alkenyl is C 14 -C 22 Alkenyl, preferably a straight chain C 14 -C 22 Alkenyl, for example, (18)R 2 In the above, C1-C 22 The alkyl group is C2-C 20 The alkyl group is preferably a straight chain C2-C 20 The alkyl group, for example, (19)R 2 In the C2-C 22 Alkenyl is C 14 -C 22 Alkenyl, preferably a straight chain C 14 -C 22 Alkenyl, for example, (20)R 2 In the above, the one or more R 2-1 Substituted C1-C 22 Alkyl is an R 2-1 Substituted C3-C6 alkyl, for example, (21)R 3 In the above, C1-C 22 The alkyl group is a C1-C4 alkyl group, for example, (22)R 3 In the above, the one or more R 3-1 Substituted C1-C 22 Alkyl is an R 3-1 Substituted C1-C3 alkyl, for example, and (23)R 3-1 In the formula (C3-C6), the C3-C6 cycloalkyl group is 4. The compound of formula I or a pharmaceutically acceptable salt thereof according to claim 1, characterized in that: The compound as shown in formula I satisfies one or more of the following conditions: (1) R, wherein the a In the substituted -(CH2)m-, the plurality is 2-14, for example, 2, 3, 4, 5, 6, 7, 8 or 12; (2) In R, 0 to 12 -CH2- in the -(CH2)m- are optionally and independently replaced by O, S, -NR b -, Sub-C6-C 12 Aryl, C3-C6 cycloalkylene, 1 or more R c Substituted C6-C 12 The aryl group and the 9,9-diphenylfluorenyl group are replaced by 1 to 13 -CH2- in the -(CH2)m-, and m can be 5-36, for example (3) In R, 0 to 12 -CH2- in the -(CH2)m- are optionally and independently replaced by O, S, -NR b -, Sub-C6-C 12 Aryl, C3-C6 cycloalkylene, 1 or more R c Substituted C6-C 12 Aryl and 9,9-diphenylfluorenyl are substituted with 1 to 2 -CH2- in the -(CH2)m- being optionally substituted with S, and m can be 1-6, for example (4) In R, 0 to 12 -CH2- in the -(CH2)m- are optionally and independently replaced by O, S, -NR b -, Sub-C6-C 12 Aryl, C3-C6 cycloalkylene, 1 or more R c Substituted C6-C 12 The aryl and 9,9-diphenylfluorenyl groups are replaced by 1 to 2 -CH2- in the -(CH2)m- group, which are optionally replaced by C6-C 12 Aryl or 1 or more R c Substituted C6-C 12 Aryl substitution, m can be 1-6, for example (5) In R, 0 to 12 -CH2- in the -(CH2)m- are optionally and independently replaced by O, S, -NR b -, Sub-C6-C 12 Aryl, C3-C6 cycloalkylene, 1 or more R c Substituted C6-C 12 The aryl and 9,9-diphenylfluorenyl groups are substituted by 1 to 6 -CH2- in the -(CH2)m- group, which are optionally replaced by O and C6-C 12 Aryl substitution, e.g. (6)R b wherein the C1-C6 alkyl group is a C1-C4 alkyl group, for example, a methyl group or an ethyl group; (7) The one or more R b1 The C1-C6 alkyl in the substituted C1-C6 alkyl is a C1-C4 alkyl; for example, ethyl; (8)R 1 In the C2-C 22 Alkynyl is a straight chain C2-C 20 Alkynyl groups, for example, (9)R 1 In the C2-C 22 0 to 8 -CH2- in the alkynyl group are optionally independently replaced by O or S to form the C2-C 22 0 to 8 -CH2- in the alkynyl group are optionally replaced by O; for example, (10)R 1-1 In the C6-C 12 Aryl is phenyl; (11)R 1-1 wherein the C3-C6 cycloalkyl group is a cyclohexyl group; (12)R 2 In the above, C1-C 22 The alkyl group is C2-C 20 The alkyl group, for example, (13)R 2 In the C2-C 22 The alkenyl groups are independently C2-C 22 Alkenyl, preferably a straight chain C2-C 10 Alkenyl, for example, (14)R 2 In the C2-C 22 Alkynyl is C2-C6 alkynyl, preferably a straight-chain C2-C6 alkynyl, for example, (15)R 2 In the C2-C 22 0 to 8 -CH2- in the alkynyl group are optionally replaced by O or S to form the C2-C 22 0 to 8 -CH2- in the alkynyl group are optionally replaced by O; for example, (16)R 2 In the above, the one or more R 2-1 Substituted C1-C 22 The alkyl group may be 2-1 Substituted C1-C6 alkyl, for example, (17)R 2 wherein the C3-C6 cycloalkyl group is a cyclohexyl group; (18)R 2 In the heterocycloalkyl group of the 3-7 membered ring, the heteroatom is N or O; for example, (19)R 2-1 In the C6-C 12 Aryl is phenyl; (20)R 2-1 In the above, the one or more R 2d3 Substituted C6-C 12 Aryl is an aryl group consisting of one or more R 2d3 Substituted C6-C 12 Aryl; for example, (21)R 2-1 wherein the C3-C6 cycloalkyl group is a cyclohexyl group; (22)R 2-1 In the above, the "5-10 membered heteroaryl group having 1, 2 or 3 heteroatoms selected from N, O and S" is a 5-membered heteroaryl group substituted by O, for example, (23)R 2d3 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, bromine; (24)R 2f In the above, the C1-C6 alkyl group is independently a C1-C4 alkyl group; for example, a methyl group; (25) In the halogenated C1-C6 alkyl group, the halogenated group is substituted by halogen, and the halogenated group is fluorine, chlorine, bromine or iodine; the C1-C6 alkyl group is a C1-C4 alkyl group; (26)R 3 In the above, C1-C 22 The alkyl group may be a C1-C6 alkyl group, for example, and (27)R 3 In the C2-C 22 Alkenyl is C2-C4 alkenyl, for example, 5. The compound of formula I or a pharmaceutically acceptable salt thereof according to claim 1, characterized in that: The compound as shown in formula I satisfies one or more of the following conditions: (1) n is 5-12; (2) R is -(CH2)m- or is replaced by one or more R a substituted -(CH2)m-; wherein 0 to 12 -CH2- in said -(CH2)m- are optionally replaced by O, S, sub-C6-C 12 Aryl, 1 or more R c Substituted C6-C 12 Aryl and 9,9-diphenylfluorenyl are substituted, and m is 1-27, for example, Preferably, R is -(CH2)m- or is replaced by one or more R a Substituted -(CH2)m-; the -(CH2)m- satisfies any of the following conditions: (1) 1 to 12 -CH2- in -(CH2)m- are optionally replaced by O; (2) 1 to 6 -CH2- in the -(CH2)m- are optionally and independently replaced by O and C6-C 12 Aryl substitution; for example, R is For example, R is For example, R is (3)R 1 C1-C 22 Alkyl, C2-C 22 Alkenyl, C2-C 22 Alkynyl or one or more R 1-1 Substituted C1-C 22 Alkyl, the C2-C 22 0 to 5 -CH2- in the alkynyl group are optionally substituted by O; for example, Preferably, R 1 For C8-C 18 Alkyl, C3-C 18 Alkenyl, C3-C 18 Alkynyl or one or more R 1-1 Substituted C1-C6 alkyl, the C2-C 22 0 to 5 -CH2- in the alkynyl group are optionally substituted by O; for example, More preferably, R 1 For C8-C 18 Alkyl groups, such as R 1 for For example, R 1 for (4) Each R 1-1 For-NR b R b , hydroxyl, C6-C 12 Aryl or C3-C6 cycloalkyl; (5)R 2 C1-C 22 Alkyl, C2-C 22 Alkenyl, C2-C 22 Alkynyl, with one or more R 2-1 Substituted C1-C 22 Alkyl, C3-C6 cycloalkyl, "3-7 membered heterocycloalkyl having 1, 2 or 3 heteroatoms selected from N, O and S" or "substituted by 1 or more R 2f The substituted "heteroatom is selected from 1, 2 or 3 of N, O and S, and the number of heteroatoms is 1, 2 or 3 3-membered heterocycloalkyl", the C2-C 22 0 to 5 -CH2- in the alkynyl group are optionally substituted by O; for example, Preferably, R 2 C1-C 18 Alkyl, C3-C 18 Alkenyl, C3-C 18 Alkynyl, with one R 2-1 Substituted C1-C6 alkyl, C3-C6 cycloalkyl, "3-7 membered heterocycloalkyl having 1, 2 or 3 heteroatoms selected from N, O and S" or substituted by 1 or more R 2f The substituted "heteroatom is selected from 1, 2 or 3 of N, O and S, and the number of heteroatoms is 1, 2 or 3 3-membered heterocycloalkyl", the C2-C 22 0 to 5 -CH2- in the alkynyl group are optionally substituted by O; for example, (6)R 2-1 For-NR b R b , hydroxyl, C6-C 12 Aryl, one or more R 2d3 Substituted C6-C 12 Aryl, C3-C6 cycloalkyl or "a 5-10 membered heteroaryl group having 1, 2 or 3 heteroatoms selected from N, O and S"; (7) Each R b are independently hydrogen, C1-C6 alkyl, C6-C 12 Aryl or one or more R b1 Substituted C1-C6 alkyl; (8) Each R 2d3 are independently halogen; (9) Each R 2e and R 2f are independently C1-C6 alkyl; (10)X is For example, X is and (11)R 3 is hydrogen, C1-C 22 Alkyl, with one or more R 3-1 Substituted C1-C 22 Alkyl or C2-C 22 alkenyl, for example, hydrogen, Preferably, R 3 is hydrogen, C1-C 22 Alkyl or C2-C 22 alkenyl, for example, hydrogen, 6. The compound of formula I or a pharmaceutically acceptable salt thereof according to claim 1 or 2, characterized in that: The compound as shown in formula I satisfies one or more of the following conditions: (1) n is 8-11; (2) R is -(CH2)m- or is replaced by one or more R a substituted -(CH2)m-; wherein 0 to 10 -CH2- in said -(CH2)m- are optionally replaced by O, S, sub-C6-C 12 Aryl and 1 or more R c Substituted C6-C 12 Aryl substituted, m is 1-27, for example, Preferably, R is -(CH2)m- or is replaced by 1-4 R a substituted -(CH2)m-; wherein 0 to 4 -CH2- in said -(CH2)m- are optionally replaced by O and C6-C 12 Aryl substituted, m is 3-11; for example, For example, For example, Further example, (3) Each R a are independently hydroxyl, C1-C6 alkyl, halogen or C1-C4 heteroalkyl; the heteroatom species in the C1-C4 heteroalkyl is O, S or N, and the number of heteroatoms is 1, 2 or 3; preferably, each R a are independently hydroxyl or C1-C6 alkyl; (4) Each R c are independently nitro or C1-C6 alkyl; (5)R 1 C1-C 22 Alkyl or C2-C 22 Alkenyl, for example, Preferably, R 1 For C8-C 18 Alkyl groups, for example, (6)R 2 C1-C 22 Alkyl, C2-C 22 Alkenyl or one or more R 2-1 Substituted C1-C 22 Alkyl groups, for example, Preferably, R 2 C4-C 18 Alkyl or an R 2-1 Substituted C1-C5 alkyl, for example, (7)R 2-1 For-NR b R b or hydroxyl; (8) Each R b are independently hydrogen or C1-C6 alkyl; (9)X is Preferably, X is (10)R 3 is hydrogen, C1-C 22 Alkyl or one or more R 3-1 Substituted C1-C 22 Alkyl groups, for example, For example, R 3 is hydrogen; and (11)R 3-1 It is a C3-C6 cycloalkyl group.

7. The compound of formula I or a pharmaceutically acceptable salt thereof according to claim 1, characterized in that: The compound as shown in formula I satisfies one or more of the following conditions: (1) n is 5-15, for example 8-15; (2) R is -(CH2)m-, and 0 -CH2- in said -(CH2)m- are substituted; and (3)R 2 C1-C 22 Alkyl or one or more R 2-1 Substituted C1-C 22 Alkyl, each R 2-1 are independently hydroxyl.

8. The compound of formula I or a pharmaceutically acceptable salt thereof according to claim 1, characterized in that: The compound as shown in formula I satisfies one or more of the following conditions: (1) n is 5-12; (2) R is -(CH2)m- or is replaced by one or more R a Substituted -(CH2)m-; 0 to 12 -CH2- in said -(CH2)m- are optionally independently replaced by O, and m is 1-19, for example, For example, Preferably, R is -(CH2)m-; m is 1-6, for example, For example, (3) Each R a are independently C1-C6 alkyl; (4)R 1 C1-C 22 Alkyl or C2-C 22 Alkenyl; for example, For example, Further, for example, More for example, (5)R 2 C1-C 22 Alkyl, C2-C 22 Alkenyl, C2-C 22 Alkynyl, with one R 2-1 Substituted C1-C6 alkyl, C3-C6 cycloalkyl, "3-7 membered heterocycloalkyl having 1, 2 or 3 heteroatoms selected from N, O and S" or substituted by 1 or more R 2f Substituted "3-7 membered heterocycloalkyl group having 1, 2 or 3 heteroatoms selected from N, O and S"; for example, Better, R 2 C1-C 12 Alkyl, C2-C 22 Alkenyl, C2-C 22 Alkynyl, with one R 2-1 Substituted C1-C6 alkyl, C3-C6 cycloalkyl or "3-7 membered heterocycloalkyl having 1, 2 or 3 heteroatoms selected from N, O and S"; for example, For example, (6)R 2-1 For-NR b R b , hydroxyl, C6-C 12 Aryl, one or more R 2d3 Substituted C6-C 12 Aryl or "a 5-10 membered heteroaryl group having 1, 2 or 3 heteroatoms selected from N, O and S"; for example, -NR b R b , hydroxyl, C6-C 12 Aryl or one or more R 2d3 Substituted C6-C 12 Aryl; also for example, -NR b R b ; and (7) each R b are independently C1-C6 alkyl.

9. The compound of formula I or a pharmaceutically acceptable salt thereof according to claim 1, characterized in that: The compound as shown in formula I satisfies one or more of the following conditions: (1) R is -(CH2)m-, wherein 0 to 3 -CH2- in said -(CH2)m- are optionally replaced by O, and m is 1-12; for example, (2)R 2 C1-C 22 Alkyl, C2-C 22 Alkenyl, C2-C 22 Alkynyl, with one R 2-1 Substituted C1-C 22 Alkyl, C3-C6 cycloalkyl or one or more R 2f Substituted "3-7 membered heterocycloalkyl group having 1, 2 or 3 heteroatoms selected from N, O and S"; for example, (3) The weight average molecular weight of the compound represented by formula I is 1000-10000.

10. The compound of formula I or a pharmaceutically acceptable salt thereof according to claim 1, characterized in that: The compound as shown in formula I satisfies one or both of the following conditions: (1)R 2 C1-C 22 Alkyl, C2-C 22 Alkenyl, with one R 2-1 Substituted C1-C6 alkyl or 1 or more R 2f Substituted "3-7 membered heterocycloalkyl group having 1, 2 or 3 heteroatoms selected from N, O and S"; for example, and (2) R is -(CH2)m-, m is 1-6; for example, R 1 For C8-C 18 Alkyl groups, such as R 1 for 11. The compound of formula I or a pharmaceutically acceptable salt thereof according to claim 1, characterized in that: The compound as shown in formula I satisfies one or both of the following conditions: (1)R 2 C1-C 22 Alkyl, C2-C 22 Alkenyl or one or more R 2-1 Substituted C1-C 22 Alkyl; for example, and (2) R is -(CH2)m-, wherein 0 to 6 -CH2- in said -(CH2)m- are optionally independently replaced by O, and m is 8-14, for example, R 1 For C8-C 18 Alkyl groups, such as R 1 for 12. The compound of formula I or a pharmaceutically acceptable salt thereof according to claim 1 or 2, characterized in that: R is -(CH2)m- or 1-4 R a substituted -(CH2)m-; wherein 0 to 4 -CH2- in said -(CH2)m- are optionally replaced by O and C6-C 12 Aryl substituted, m is 3-11; for example, For example, 13. The compound of formula I or a pharmaceutically acceptable salt thereof according to claim 1 or 2, characterized in that: The compound as shown in formula I satisfies one or both of the following conditions: (1) n is 8-11; and (2) R is -(CH2)m-; 0 to 3 -CH2- in said -(CH2)m- are optionally substituted by O, and m is 4-11; for example, For example, 14. The compound of formula I or a pharmaceutically acceptable salt thereof according to claim 1 or 2, characterized in that: The compound of formula I satisfies one or more of the following conditions: (1) R is -(CH2)m-; 0 to 3 -CH2- in the -(CH2)m- are optionally substituted by O, and m is 4-11; for example, (2)R 1 C 10 -C 16 Alkyl groups, for example, (3)R 2 C4-C 16 Alkyl or an R 2-1 Substituted C1-C5 alkyl, for example, For example, and (4) R 2-1 It is hydroxyl.

15. The compound of formula I or a pharmaceutically acceptable salt thereof according to claim 1 or 2, characterized in that: R 2 C4-C 16 Alkyl or an R 2-1 Substituted C1-C5 alkyl, for example, 16. The compound of formula I or a pharmaceutically acceptable salt thereof according to claim 1 or 2, characterized in that: The compound as shown in Formula I satisfies one or more of the following conditions: (1) n is 8-9; (2) R is -(CH2)m-; m is 4-6; for example, (3)R 1 C 14 -C 16 Alkyl groups, for example, and (4) R 2 C4-C 16 Alkyl or an R 2-1 Substituted C1-C5 alkyl, for example, For example, For example, 17. The compound of formula I or a pharmaceutically acceptable salt thereof according to claim 1 or 2, characterized in that: The compound as shown in Formula I satisfies one or more of the following conditions: (1) n is 9-10; (2) R is -(CH2)m-; 0 to 3 -CH2- in said -(CH2)m- are optionally substituted by O, and m is 4-11; for example, (3)R 1 For C8-C 12 Alkyl groups, for example, and (4) R 2 C4-C 10 Alkyl or an R 2-1 Substituted C1-C5 alkyl, for example, For example, 18. The compound of formula I or a pharmaceutically acceptable salt thereof according to claim 1 or 2, characterized in that: The compound as shown in formula I satisfies any of the following schemes: Scenario 1: n is 8-11; R is -(CH2)m- or is replaced by one or more R a substituted -(CH2)m-; 0 to 10 -CH2- in said -(CH2)m- are optionally replaced by O, S, sub-C6-C 12 Aryl and 1 or more R c Substituted C6-C 12 Aryl substituted, m is 1-27, for example, Each R a are independently hydroxyl, C1-C6 alkyl, halogen or C1-C4 heteroalkyl; the heteroatom species in the C1-C4 heteroalkyl is O, S or N, and the number of heteroatoms is 1, 2 or 3; Each R c are independently nitro or C1-C6 alkyl; R 1 C1-C 22 Alkyl or C2-C 22 Alkenyl, for example, R 2 C1-C 22 Alkyl, C2-C 22 Alkenyl or one or more R 2-1 Substituted C1-C 22 Alkyl groups, for example, R 2-1 For-NR b R b or hydroxyl; Each R b are independently hydrogen or C1-C6 alkyl; X is R 3 is hydrogen, C1-C 22 Alkyl or one or more R 3-1 Substituted C1-C 22 Alkyl groups, for example, R 3-1 is a C3-C6 cycloalkyl group; Preferably, the weight average molecular weight of the compound as shown in Formula I is 2030-5460, preferably 2600-4200, for example, 2600, 2700, 2900, 3000, 3100, 3400, 3500, 4100 or 4200; Scenario 2: n is 8-11; R is -(CH2)m- or 1-4 R a substituted -(CH2)m-; wherein 0 to 4 -CH2- in said -(CH2)m- are optionally replaced by O and C6-C 12 Aryl substituted, m is 3-11; for example, Each R a are independently hydroxyl or C1-C6 alkyl; R 1 For C8-C 18 Alkyl groups, for example, R 2 C4-C 18 Alkyl or an R 2-1 Substituted C1-C5 alkyl, for example, R 2-1 For-NR b R b or hydroxyl; Each R b are independently hydrogen or C1-C6 alkyl; X is R 3 is hydrogen; Preferably, the weight average molecular weight of the compound as shown in Formula I is 2030-5460, preferably 2600-4200, for example, 2600, 2700, 2900, 3000, 3100, 3400, 3500, 4100 or 4200; Scenario 3: n is 8-11; R is -(CH2)m- or 1-4 R a substituted -(CH2)m-; wherein 0 to 4 -CH2- in said -(CH2)m- are optionally replaced by O and C6-C 12 Aryl substituted, m is 3-11; for example, Each R a are independently hydroxyl or C1-C6 alkyl; R 1 For C8-C 18 Alkyl groups, for example, R 2 C4-C 18 Alkyl or an R 2-1 Substituted C1-C5 alkyl, for example, R 2-1 For-NR b R b or hydroxyl; Each R b are independently hydrogen or C1-C6 alkyl; X is R 3 is hydrogen; Preferably, the weight average molecular weight of the compound as shown in Formula I is 1890-5330, preferably 2700-4100, for example, 2700, 3100, 3500 or 4100; Solution 4: n is 8-11; R is -(CH2)m- or 1-4 R a substituted -(CH2)m-; wherein 0 to 4 -CH2- in said -(CH2)m- are optionally replaced by O and C6-C 12 Aryl substituted, m is 3-11; for example, Each R a are independently hydroxyl or C1-C6 alkyl; R 1 For C8-C 18 Alkyl groups, for example, R 2 C4-C 18 Alkyl or an R 2-1 Substituted C1-C5 alkyl, for example, R 2-1 For-NR b R b or hydroxyl; Each R b are independently hydrogen or C1-C6 alkyl; X is R 3 is hydrogen; Preferably, the weight average molecular weight of the compound as shown in Formula I is 1890-4550, preferably 2700-3500, for example, 2700, 3100 or 3500; Solution 5: n is 8-11; R is -(CH2)m- or 1-4 R a substituted -(CH2)m-; wherein 0 to 4 -CH2- in said -(CH2)m- are optionally replaced by O and C6-C 12 Aryl substituted, m is 3-11; for example, Each R a are independently hydroxyl or C1-C6 alkyl; R 1 For C8-C 18 Alkyl groups, for example, R 2 C4-C 18 Alkyl or an R 2-1 Substituted C1-C5 alkyl, for example, R 2-1 For-NR b R b or hydroxyl; Each R b are independently hydrogen or C1-C6 alkyl; X is R 3 is hydrogen; Solution 6: n is 8-11; R is -(CH2)m- or 1-4 R a substituted -(CH2)m-; wherein 0 to 4 -CH2- in said -(CH2)m- are optionally replaced by O and C6-C 12 Aryl substituted, m is 3-11; for example, Each R a are independently hydroxyl or C1-C6 alkyl; R 1 For C8-C 18 Alkyl groups, for example, R 2 C4-C 18 Alkyl or an R 2-1 Substituted C1-C5 alkyl, for example, R 2-1 For-NR b R b or hydroxyl; Each R b are independently hydrogen or C1-C6 alkyl; X is R 3 is hydrogen; Preferably, the weight average molecular weight of the compound as shown in Formula I is 2030-5460, preferably 2600-4200, for example, 2600, 2700, 2900, 3000, 3100, 3400, 3500 or 4200; Solution 7: n is 8-11; R is -(CH2)m- or 1-4 R a substituted -(CH2)m-; wherein 0 to 4 -CH2- in said -(CH2)m- are optionally replaced by O and C6-C 12 Aryl substituted, m is 3-11; for example, Each R a are independently hydroxyl or C1-C6 alkyl; R 1 For C8-C 18 Alkyl groups, for example, R 2 C4-C 18 Alkyl or an R 2-1 Substituted C1-C5 alkyl, for example, R 2-1 For-NR b R b or hydroxyl; Each R b are independently hydrogen or C1-C6 alkyl; X is R 3 is hydrogen; Preferably, the weight average molecular weight of the compound as shown in Formula I is 2030-5460, preferably 2600-4200, for example, 2600, 2900, 3000, 3100, 3400 or 4200; Solution 8: n is 8-11; R is -(CH2)m-; 0 to 3 -CH2- in said -(CH2)m- are optionally substituted by O, and m is 4-11; for example, R 1 For C8-C 18 Alkyl groups, for example, R 2 C4-C 18 Alkyl or an R 2-1 Substituted C1-C5 alkyl, for example, R 2-1 For-NR b R b or hydroxyl; Each R b are independently hydrogen or C1-C6 alkyl; X is R 3 is hydrogen; Preferably, the weight average molecular weight of the compound as shown in Formula I is 1890-5330, preferably 2700-4100, for example, 2700, 3100, 3500 or 4100; Solution 9: n is 8-11; R is -(CH2)m-; 0 to 3 -CH2- in said -(CH2)m- are optionally substituted by O, and m is 4-11; for example, R 1 For C8-C 18 Alkyl groups, for example, R 2 C4-C 18 Alkyl or an R 2-1 Substituted C1-C5 alkyl, for example, R 2-1 For-NR b R b or hydroxyl; Each R b are independently hydrogen or C1-C6 alkyl; X is R 3 is hydrogen; Preferably, the weight average molecular weight of the compound as shown in Formula I is 1890-4500, preferably 2700-3500, for example, 2700, 3100 or 3500; Solution 10: n is 8-10; R is -(CH2)m-; 0 to 3 -CH2- in said -(CH2)m- are optionally substituted by O, and m is 4-11; for example, R 1 C 10 -C 16 Alkyl groups, for example, R 2 C4-C 16 Alkyl or an R 2-1 Substituted C1-C5 alkyl, for example, R 2-1 For-NR b R b or hydroxyl; Each R b are independently hydrogen or C1-C6 alkyl; X is R 3 is hydrogen; Preferably, the weight average molecular weight of the compound as shown in Formula I is 2450-5330, preferably, 3500-4100, for example, 3500 or 4100; Solution 11: n is 8-10; R is -(CH2)m-; 0 to 3 -CH2- in said -(CH2)m- are optionally substituted by O, and m is 4-11; for example, R 1 C 10 -C 16 Alkyl groups, for example, R 2 C4-C 16 Alkyl or an R 2-1 Substituted C1-C5 alkyl, for example, R 2-1 is hydroxyl group; X is R 3 is hydrogen; Preferably, the weight average molecular weight of the compound as shown in Formula I is 2450-5330, preferably, 3500-4100, for example, 3500 or 4100; Solution 12: n is 8-10; R is -(CH2)m-; 0 to 3 -CH2- in said -(CH2)m- are optionally substituted by O, and m is 4-11; for example, R 1 C 10 -C 16 Alkyl groups, for example, R 2 C4-C 16 Alkyl or an R 2-1 Substituted C1-C5 alkyl, for example, R 2-1 For-NR b R b or hydroxyl; Each R b are independently C1-C6 alkyl; X is R 3 is hydrogen; Preferably, the weight average molecular weight of the compound as shown in Formula I is 2450-5330, preferably 3500-4100, for example, 3500 or 4100; Solution 13: n is 8-9; R is -(CH2)m-; m is 4-6; for example, R 1 C 14 -C 16 Alkyl groups, for example, R 2 C4-C 16 Alkyl or an R 2-1 Substituted C1-C5 alkyl, for example, R 2-1 For-NR b R b or hydroxyl; Each R b are independently hydrogen or C1-C6 alkyl; X is R 3 is hydrogen; Preferably, the weight average molecular weight of the compound as shown in Formula I is 2450-4550, for example, 3500; Solution 14: n is 8-9; R is -(CH2)m-; m is 4-6; for example, R 1 C 14 -C 16 Alkyl groups, for example, R 2 C4-C 16 Alkyl or an R 2-1 Substituted C1-C5 alkyl, for example, R 2-1 For-NR b R b or hydroxyl; Each R b are independently hydrogen or C1-C6 alkyl; X is R 3 is hydrogen; Preferably, the weight average molecular weight of the compound as shown in Formula I is 2450-4550, for example, 3500; Solution 15: n is 8-9; R is -(CH2)m-; m is 4-6; for example, R 1 C 14 -C 16 Alkyl groups, for example, R 2 C4-C 16 Alkyl or an R 2-1 Substituted C1-C5 alkyl, for example, R 2-1 is hydroxyl group; X is R 3 is hydrogen; Preferably, the weight average molecular weight of the compound as shown in Formula I is 2450-4550, for example, 3500; Scheme 16: n is 9-10; R is -(CH2)m-; 0 to 3 -CH2- in said -(CH2)m- are optionally substituted by O, and m is 4-11; for example, R 1 For C8-C 12 Alkyl groups, for example, R 2 C4-C 10 Alkyl or an R 2-1 Substituted C1-C5 alkyl, for example, R 2-1 For-NR b R b or hydroxyl; Each R b are independently hydrogen or C1-C6 alkyl; X is R 3 is hydrogen; preferably, the weight average molecular weight of the compound as shown in Formula I is 2870-5330, for example, 4100; Solution 17: n is 9-10; R is -(CH2)m-; 0 to 3 -CH2- in said -(CH2)m- are optionally substituted by O, and m is 4-11; for example, R 1 For C8-C 12 Alkyl groups, for example, R 2 C4-C 10 Alkyl groups, for example, X is R 3 is hydrogen; Preferably, the weight average molecular weight of the compound as shown in Formula I is 2870-5330, for example, 4100.

19. The compound of formula I or a pharmaceutically acceptable salt thereof according to claim 1, characterized in that: The compound as shown in formula I is any one of the compounds in the following table, 20. The compound of formula I or a pharmaceutically acceptable salt thereof according to claim 1 or 2, characterized in that: The compound as shown in formula I is any one of the compounds in Table 1 below, Table 1 21. A blank polymer-lipid nanoparticle, characterized in that: It includes an ionizable polymer PBAE, and the ionizable polymer PBAE is a compound as shown in formula I as described in any one of claims 1 to 20 or a pharmaceutically acceptable salt thereof.

22. The blank polymer-lipid nanoparticle of claim 21, wherein: The blank polymer-lipid nanoparticles satisfy one or more of the following conditions: (1) The blank polymer-lipid nanoparticles further include a diluent; (2) the blank polymer-lipid nanoparticles further include auxiliary phospholipids; (3) the blank polymer-lipid nanoparticles further include sterol; and (4) the blank polymer-lipid nanoparticles further include lipids that inhibit particle aggregation.

23. The blank polymer-lipid nanoparticle of claim 22, wherein: The blank polymer-lipid nanoparticles satisfy one or more of the following conditions: (1) The diluent is an organic phase and an aqueous phase. Preferably, the organic phase is ethanol, acetone, tetrahydrofuran or acetonitrile miscible with water, preferably ethanol; the aqueous phase can be sodium citrate buffer with a pH of 3 or sodium acetate buffer with a pH of 5, preferably sodium acetate; (2) The auxiliary phospholipid is DSPC, DOPE, DOPC, DSPE and its derivatives, preferably DOPE; (3) The sterol is cholesterol and its derivatives, preferably cholesterol; (4) The lipid that inhibits particle aggregation can be polyethylene glycol and its derivatives, preferably DMG-PEG; (5) In the diluent, the volume ratio of the organic phase to the aqueous phase may be 1:1-1:3, preferably 1:2 and 1:3; (6) In the blank polymer-lipid nanoparticles, the molar ratio of the ionizable polymer PBAE to the auxiliary phospholipid is 1:0.03-2.5, preferably 1:1 or 1:0.48; (7) In the blank polymer-lipid nanoparticles, the molar ratio of the ionizable polymer PBAE to sterol is 1:0.67-6.5, preferably 1:2 or 1:2.40; and (8) in the blank polymer-lipid nanoparticles, the molar ratio of the ionizable polymer PBAE to the particle aggregation inhibiting lipid is 1:0.01-1, preferably 1:0.20 or 1:0.

12.

24. The blank polymer-lipid nanoparticle of claim 23, wherein: The blank polymer-lipid nanoparticles are composed of the ionizable polymer PBAE and common lipids, wherein the common esters are auxiliary phospholipids, sterols and lipids that inhibit particle aggregation; preferably, the blank polymer-lipid nanoparticles are composed of the ionizable polymer PBAE, DOPE, cholesterol and DMG-PEG, and the molar ratios of the ionizable polymer PBAE, DOPE, cholesterol and DMG-PEG are 23.8:23.8:47.6:4.8 and 25:12:60:

3.

25. A nucleic acid drug polymer-lipid nanoparticle, characterized in that: It includes a nucleic acid drug and a blank polymer-lipid nanoparticle as described in any one of claims 21-24. Preferably, the nucleic acid drug may be a conventional nucleic acid molecule in the art; for example, the nucleic acid molecule may be mRNA, saRNA, cirRNA, miRNA, shRNA, siRNA, dsDNA, pDNA, preferably mRNA.

26. The nucleic acid drug polymer-lipid nanoparticle of claim 25, wherein: The nucleic acid drug polymer-lipid nanoparticles also include a diluent.

27. The nucleic acid drug polymer-lipid nanoparticle of claim 26, wherein: The nucleic acid drug polymer-lipid nanoparticles meet one or more of the following conditions: (1) The diluent may be an organic phase and an aqueous phase. Preferably, the organic phase is ethanol, acetone, tetrahydrofuran, acetonitrile miscible with water, preferably ethanol; the aqueous phase is sodium citrate buffer at pH=3 or sodium acetate buffer at pH=5, preferably sodium acetate; (2) In the diluent, the volume ratio of the organic phase to the aqueous phase is 1:1-1:3; and (3) in the nucleic acid drug polymer-lipid nanoparticles, the N / P ratio of the ionizable polymer PBAE and the nucleic acid molecule may be 5:1-50:1, preferably 25:1, 12.5:1 or 21:1; Preferably, the nucleic acid drug polymer-lipid nanoparticles consist of the nucleic acid drug and the blank polymer-lipid nanoparticles.

28. Use of an ionizable polymer PBAE in preparing a delivery system, characterized in that: The ionizable polymer PBAE is a compound as shown in formula I as described in any one of claims 1 to 20 or a pharmaceutically acceptable salt thereof, and the delivery system is a system for delivering a therapeutic agent and / or a preventive agent to the lungs and / or liver; the therapeutic agent and / or the preventive agent is a nucleic acid drug.

29. Use of the ionizable polymer PBAE according to claim 28 in preparing a delivery system, characterized in that: It satisfies one or more of the following conditions: (1) The delivery is targeted delivery; (2) The delivery system is a blank polymer-lipid nanoparticle as described in any one of claims 12 to 15; and (3) the ionizable polymer PBAE, blank polymer-lipid nanoparticles and nucleic acid drugs are as described in any one of claims 1-18.

30. An application of an ionizable polymer PBAE as a pharmaceutical excipient, characterized in that: The ionizable polymer PBAE is a compound of formula I as described in any one of claims 1 to 20 or a pharmaceutically acceptable salt thereof, and the functions of the pharmaceutical excipient include nucleic acid encapsulation, lung and / or liver targeted delivery, promoting effective cell uptake or promoting lysosomal escape.

31. Use of composition A in preparing a delivery system or a drug for treating and / or preventing a disease, characterized in that: The disease is a lung or / and liver-related disease, the composition nucleic acid drug polymer-lipid nanoparticle includes an ionizable polymer PBAE, the ionizable polymer PBAE is a compound shown in Formula I or a pharmaceutically acceptable salt thereof, and the delivery system is as described in claim 28 or 29.

32. Use of the composition A as claimed in claim 31 in preparing a delivery system or a drug for treating and / or preventing a disease, characterized in that: The composition A also includes one or more of auxiliary phospholipids, sterols, lipids that inhibit particle aggregation and / or nucleic acid drugs. In the composition A, the auxiliary phospholipids, sterols, lipids that inhibit particle aggregation and / or nucleic acid drugs are as described in any one of claims 21-27.

33. Use of the composition A as claimed in claim 32 in preparing a delivery system or a drug for treating and / or preventing a disease, characterized in that: The composition A satisfies at least one of the following conditions: (1) In the composition A, the ionizable polymer PBAE and one or more of the auxiliary phospholipids, sterols, and lipids that inhibit particle aggregation form blank polymer-lipid nanoparticles as described in any one of claims 12 to 15; (2) In the composition A, the blank polymer-lipid nanoparticles and the nucleic acid drug form the nucleic acid drug polymer-lipid nanoparticles according to any one of claims 16 to 18; (3) In the composition A, the average particle size of the blank polymer-lipid nanoparticles of the composition may be 30-200 nm, and the surface potential may be -20-+20 mV; (4) In the composition A, the average particle size of the nucleic acid drug polymer-lipid nanoparticles in the composition can be 50-300 nm, and the surface potential can be -20-+20 mV.

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