Nitrogen-containing heterocycle-branched cationic lipid

Abstract

Provided in the present invention is a nitrogen-containing heterocycle-branched cationic lipid. The structure thereof is as represented by general formula (1), wherein the definition of each symbol is consistent with that described herein. The nitrogen-containing heterocycle-branched cationic lipid has a nitrogen-containing heterocycle as a branched core, an amino acid or an amino acid derivative as a linker arm, and a saturated or unsaturated hydrocarbon group as a tail chain; and has the advantages of low toxicity, low immunogenicity and high biocompatibility. In the new cationic lipid of the present invention, the electropositivity of the nitrogen on the nitrogen-containing heterocycle is delocalized to the whole ring, so that the cationic lipid shows higher transfection efficiency and lower cytotoxicity. The new cationic lipid of the present invention contains one or more biodegradable groups between the nitrogen-containing heterocycle and the hydrophobic tail, and the presence of the degradable groups enables a lipid nanoparticle (LNP) prepared from the cationic lipid to be timely degraded in the endosome, such that the problem in the prior art whereby LNPs prepared from a non-degradable lipid accumulate in the endosome and acidify the endosomal environment, thereby hindering the endosomal escape of a drug molecule (such as a nucleic acid) and thus the drug delivered into a cell not being able to function is solved.

Description

A nitrogen heterocycle-branched cationic lipid Technical Field The present invention belongs to the field of drug delivery, and specifically relates to a nitrogen heterocycle-branched cationic lipid as a pharmaceutical carrier, and a lipid composition, a lipid drug composition, and their preparations and applications containing the cationic lipid. Background Art Effective in vivo delivery is a key factor for nucleic acid drugs to achieve therapeutic effects. Exogenous RNA drugs must penetrate the lipid membrane barrier to enter the cytoplasm and then be successfully translated into functional proteins. There are two obstacles in delivering RNA drugs into cells: enzymatic degradation during delivery and membrane barriers caused by electrostatic repulsion. An ideal delivery system needs to meet the following conditions: effectively encapsulate and protect the drug before reaching the target to maintain its stability; help the drug enter the cell efficiently; release the drug into the cytoplasm in a timely manner before the drug reaches the lysosome, and transcribe and translate it into functional proteins in the cytoplasm. Currently, a variety of delivery carriers have been developed to promote the cellular uptake of nucleic acid drugs and protect them from degradation. The main non-viral carriers include protamine, lipid nanoparticles (LNPs), dendritic cells, inorganic nanoparticles, etc. Among them, LNP is a relatively mature delivery technology currently used to deliver protein, nucleic acid, polypeptide drugs or gene editing tools. LNPs usually include ionizable cationic lipids, cholesterol, phospholipids, and polyethylene glycolated lipids. Among them, the ionizable cationic lipid with the largest molar proportion plays a major role in protecting nucleic acids from nuclease degradation. In addition, auxiliary lipids such as phospholipids and cholesterol can promote the stability of the preparation and membrane fusion. Ionizable cationic lipids have a nearly neutral charge at physiological pH and are easily protonated and positively charged at low pH, and can bind to the negatively charged phosphate groups on nucleic acids through electrostatic interactions. After administration at neutral or physiological pH, LNPs enter cells through endocytosis. The ionizable cationic lipids are protonated and positively charged in the acidic environment of the endosomal cavity and interact with the negative charges on the endosomal membrane, thereby disrupting the endosomal membrane and promoting the endosomal escape and release of the encapsulated nucleic acids into the cytoplasm. In the prior art WO2023232147A1, there are amino acid-branched cationic lipids, but the amino acids are used as the central core part of the entire cationic lipid. There is still a need in the art to develop novel nitrogen heterocycle-branched cationic lipids containing amino acid linkers. Summary of the Invention The present invention provides a novel nitrogen-containing heterocyclic branched cationic lipid, a preparation method thereof, a lipid composition containing the cationic lipid, a lipid drug composition and its preparation containing the lipid composition, a liposome or lipid nanoparticle containing the lipid composition, especially an LNP-nucleic acid drug composition and its preparation containing the lipid composition, which have the advantages of high delivery efficiency, low safety and toxicity, and high biocompatibility, and can improve the therapeutic and / or prophylactic effect of drugs. The above object of the present invention is achieved by the following technical solutions: An embodiment of the present invention provides a cationic lipid: A cationic lipid, characterized in that its structure is shown in the general formula (1): Or its salt, tautomer, stereoisomer, deuterated compound or solvate; Wherein, Core is a nitrogen-containing heterocyclic nucleus; L is a divalent linking group L d , said L d Selected from -(CH2) tm -, -Z-, -(CH2) tm Z-, -Z(CH2) tm -, -Z(CH2) tm Z-, -(CH2) tm Z(CH2) tm -, -Z(CH2) tm Z(CH2) tm -, -(CH2) tm Z(CH2) tm Z- and -(CH2) tm Z(CH2) tm Z(CH2) tm - any one of them, wherein, tm is independently an integer from 1 to 12 each time it appears; Z is independently -C(=O)-, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -O-, -S-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -, -NR c C(=O)NR c -, -OC(=O)NR c -, -NR c C(=O)O-, -SC(=O)NR c - and -NR c C(=O)S- any one of them, wherein, R c Is independently H or C 1-12 Alkyl; AA is a residue of aspartic acid, glutamic acid or the aforementioned amino acid derivatives; Each occurrence of B1 and B2 is independently a linking bond or C 1-20 alkylene; Each occurrence of L1, L2, L3 and L4 is independently a linking bond or a divalent linking group L a ; said L a selected from -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -NH-, -O(CH2) s O-, -S-, -S-S-, -C(=O)S-, -SC(=O)-, -NHC(=O)-, -C(=O)NH-, -NHC(=O)NH-, -OC(=O)NH-, -NR c C(=O)O-, -SC(=O)NH-, -NHC(=O)S-, -C(=S)-, -OC(=S)-, -C(=S)O-, -OC(=S)O-, -NHC(=S)-, -C(=S)NH-, -NHC(=S)NH-, -OC(=S)NH- and -NHC(=S)O-, where s is 1, 2, 3 or 4; L1 and L3 are not simultaneously a linking bond; L2 and L4 are not simultaneously a linking bond; Each occurrence of R1 and R2 is independently a C 5-30 hydrocarbyl or C 5-30 hydrocarbyl derivative; a and b are independently 1 or 2; when the -B1-L1-R1 and / or -B2-L2-R2 fragment is derived from the amino terminus of an amino acid and its derivatives, a and b are independently 1 or 2; when the -B1-L1-R1 and / or -B2-L2-R2 fragment is derived from the carboxyl terminus of an amino acid and its derivatives, a and b are independently 1; when a and b are 2, the two -B1-L1-R1 and / or -B2-L2-R2 fragments are independently the same or different; c is 2, 3 or 4. The present invention also provides a lipid composition, and the embodiments are as follows: A lipid composition containing a cationic lipid having the structure shown in formula (1). The present invention also provides a lipid pharmaceutical composition, and the embodiments are as follows: A lipid pharmaceutical composition containing a lipid composition and a drug, and the lipid composition contains a cationic lipid having the structure shown in formula (1), and the drug is selected from any one of nucleic acid drugs, gene vaccines, anti-tumor drugs, small molecule drugs, polypeptide drugs or protein drugs. The present invention also provides a preparation of a lipid pharmaceutical composition, and the embodiments are as follows: A lipid drug composition preparation, containing the aforementioned lipid drug composition and a pharmaceutically acceptable diluent or excipient. The present invention also provides a liposome or lipid nanoparticle, and the embodiments are as follows: A liposome or lipid nanoparticle, containing a lipid composition, and the lipid composition contains a cationic lipid having the structure shown in formula (1). Compared with the prior art, the present invention has the following beneficial effects: The novel cationic lipid of the present invention uses a nitrogen-containing heterocycle as the branched core, an amino acid or amino acid derivative as the linker arm, and a saturated or unsaturated hydrocarbon group as the tail chain. The cationic lipid of the present invention complexes with negatively charged drugs such as nucleic acids through electrostatic interaction, so as to effectively deliver drugs such as nucleic acids into cells. In addition, the present invention uses an amino acid or amino acid derivative with good biocompatibility as the linker arm, further improving the biocompatibility of the cationic lipid, and the raw materials of the amino acid or amino acid derivative are simple and easy to obtain, can be obtained naturally or synthesized simply, and have the advantages of simplicity, safety, and cost saving in production. The amino acid part contained in the novel cationic lipid of the present invention can also provide a tertiary amine structure while serving as a secondary branched core, and together with the nitrogen-containing heterocyclic central core, it constitutes a multi-stage tertiary amine structure, increasing the number of tertiary amines that can ionize positive charges. When preparing LNP, the dosage of the cationic lipid is less, safer, and the translation efficiency of nucleic acids is improved. One or more biodegradable groups are contained between the nitrogen-containing heterocycle and the hydrophobic tail of the novel cationic lipid of the present invention. The presence of the biodegradable groups enables the LNP-drug composition prepared therefrom to degrade in a timely manner in the body and have low cytotoxicity, solving the problem that the LNP-drug composition prepared from a cationic lipid that cannot degrade or has poor degradation performance in the prior art will accumulate in endosomes, acidify the endosomal environment, resulting in blocked endosomal escape of drugs (such as mRNA), and the drugs delivered into cells cannot fully play their roles. At the same time, these biodegradable groups are stable at physiological pH and can be hydrolyzed by enzymes in living tissue cells to form multiple low-toxicity small molecule acids, alcohols, amines, and amino acids, etc., thereby further reducing the cytotoxicity of the lipid and improving the delivery efficiency. The positive charge of the nitrogen on the nitrogen-containing heterocycle in the novel cationic lipid of the present invention will delocalize over the entire ring, making the cationic lipid show higher transfection efficiency and lower cytotoxicity. The novel cationic lipid of the present invention has strong gene complexing ability, and the cationic liposome nucleic acid drug composition prepared therefrom shows high gene transfection effect in vivo. Specifically, it can be applied to the delivery of nucleic acid drugs, gene vaccines, anti-tumor drugs, small molecule drugs, polypeptide drugs, or protein drugs, etc., so as to improve the therapeutic and / or diagnostic effects of these drugs as prophylactic agents and / or therapeutic agents. Description of the Drawings Figure 1 is the 1 1H NMR spectrum of the cationic lipid E1-1 prepared in Example 1. Figure 2 is the 1 1H NMR spectrum of the cationic lipid E2-1 prepared in Example 2. Figure 3 is the 1 1H NMR spectrum of the cationic lipid E16-1 prepared in Example 16. Figure 4 is the 1 1H NMR spectrum of the cationic lipid E30-1 prepared in Example 30. Figure 5 shows the results of high performance liquid chromatography (HPLC) test of the cationic lipid E1-1 prepared in Example 1. Figure 6 shows the results of cytotoxicity test of the LNP-mRNA pharmaceutical composition L-1 prepared in Example 33. Figure 7 shows the imaging results after injection of the LNP-mRNA pharmaceutical composition L-1 prepared in Example 33 into mice. Embodiments Term Explanation In the present invention, unless otherwise described, all technical and scientific terms used herein have the same meanings as those commonly understood by those of ordinary skill in the art. The disclosures of all patents and other publications cited herein are incorporated herein by reference in their entirety. In the case of any conflict between any description or interpretation of the terms herein and any document incorporated herein by reference, the following description and interpretation of the terms shall prevail. In the present invention, when the structures involved have isomers, any one of the isomers may be used without special designation. For example, for a structure with cis-trans isomers, it may be either the cis structure or the trans structure; for a structure with E / Z isomers, it may be either the E structure or the Z structure; when there is optical activity, it may be either the left-handed or right-handed form. In the present invention, the interpretation of numerical ranges includes not only the numerical ranges marked with a short dash (such as 0-12), but also the numerical ranges marked with a tilde (such as 0~12), and the numerical ranges marked with "to" (such as 0 to 12, 1 to 12). In the present invention, unless otherwise specified, an integer range marked in interval form can represent the set composed of all integers within the range, and the range includes both endpoints. For example, the integer range 0-12 represents the set composed of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12. The numerical ranges in the present invention include, but are not limited to, numerical ranges represented by integers, non-integers, percentages, and fractions, and include both endpoints unless otherwise specified. In the present invention, numerical values involving "about" or "around" generally refer to a numerical range of ±10%, and in some cases, it can be enlarged to ±15%, but not exceeding ±20%, based on the preset numerical value. For example, if the molar percentage of steroid lipid in the total lipid in a solution containing a solvent is about 40%, it generally can be considered to include the case where the molar percentage of steroid lipid is 30% - 50%. In the present invention, unless otherwise specified, "any" includes any one, any two, and any two or more. In the present invention, unless otherwise specified, the terms "comprise", "include", "contain" and similar expressions shall be interpreted in an open and inclusive sense as "including but not limited to" in this specification and claims. When two or more objects in the present invention are "each independently preferably", when there are multiple levels of preference, it is not required that they are all selected from the same level of preferred groups. One can be a preference in a large range, one can be a preference in a small range, or one can be the maximum range and the other can be any preferred case, or they can be selected from the same level of preference. In the present invention, "each independently at each occurrence being" not only means that different groups can each independently be any option in the definition, but also means that when occurring at different positions in the same group, they can also each independently be any option in the definition. For example, "each independently being a linking bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -NH-, -O(CR c R c ) s O-, -S-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -, -NR c C(=O)NR c -, -OC(=O)NR c -, -NR c C(=O)O-, -SC(=O)NR c - and -NR c C(=O)S- among any one, where R c each independently at each occurrence being a hydrogen atom or C 1-12 alkyl", in the group "-NR c C(=O)NR c -", the two Rs c each independently being a hydrogen atom or C 1-12 alkyl, that is, the two Rs c can be the same or different. In the present invention, for a divalent linking group such as an alkylene group, an alkylidene group, an arylene group, an amide bond, etc., when there is no particular limitation, either of the two linking ends can be selected when it links to other groups. For example, when an amide bond is used as the divalent linking group between Group A and Group B, it can be Group A-C(=O)NH-Group B or Group B-NHC(=O)-Group A. In the present invention, when the end groups of the linking group in the structural formula are prone to confusion with the substituents contained in the linking group, is used to mark the positions where other groups are linked in the linking group. For example, in the structural formula , the is used to mark the two positions where other groups are linked in the divalent linking group. The aforementioned two structural formulas respectively represent -CH(CH2CH2CH3)2- and -CH2CH2CH(CH3)2-CH2CH2-. In the present invention, the range of the number of carbon atoms in a group is marked in subscript form at the subscript position of C, indicating the number of carbon atoms that the group has. For example, C 1-12 represents "having 1 to 12 carbon atoms", and C 1-30 represents "having 1 to 30 carbon atoms". "Substituted C 1-12 alkyl" refers to a compound obtained by substituting the hydrogen atoms of C 1-12 alkyl. "C 1-12 substituted alkyl" refers to a compound having 1 - 12 carbon atoms obtained after substituting the hydrogen atoms of the alkyl. For another example, when a group can be selected from C 1-12 alkylene, it can be any alkylene with the number of carbon atoms within the range indicated by the subscript, that is, it can be selected from any one of C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 alkylene. In the present invention, unless otherwise specified, the subscripts marked in interval form all indicate that any integer within the range can be selected, and this range includes both endpoints. In the present invention, "group" can be referred to as "bond" without changing the meaning. For example, an ether group (-O-) can also be referred to as an ether bond, and an ester group (-OC(=O)- or -C(=O)O-) can also be referred to as an ester bond. In the present invention, the "carbon chain length" between two groups refers to the shortest number of carbon atoms excluding the groups themselves. For example, for -OC(=O)CH2CH2OC(=O)- and -OC(=O)CH(CH3)CH2OC(=O)-, the carbon chain length between the two ester bonds is both 2 (which can also be referred to as C2), and for -OC(=O)CH2CH2OCH2CH2OC(=O)-, the carbon chain length between the two ester bonds is C4 (which can also be referred to as C4). In the present invention, the heteroatom is not particularly limited and includes, but is not limited to, O, S, N, P, Si, F, Cl, Br, I, B, etc. In the present invention, the heteroatom used for substitution is referred to as a "substituting atom", and any group used for substitution is referred to as a "substituent". In the present invention, "substituted" means that at least one hydrogen atom of any of the above groups (for example, an aliphatic hydrocarbon group, a hydrocarbon group, an alkyl group or an alkylene group) is replaced by a bond connected to a non-hydrogen atom, and the non-hydrogen atom is, for example, but not limited to: halogen atoms such as F, Cl, Br and I; an oxo group (=O); a hydroxyl group (-OH); a hydrocarbyloxy group (-OR d , where R d is a C 1-12 alkyl group); a carboxyl group (-COOH); an amine group (-NR c R c , and the two Rs c are each independently H, C 1-12 alkyl group); C 1-12 alkyl group and cycloalkyl group. In some embodiments, the substituent is a C 1-12 alkyl group. In other embodiments, the substituent is a cycloalkyl group. In other embodiments, the substituent is a halogenated group, such as fluoro. In other embodiments, the substituent is an oxo group. In other embodiments, the substituent is a hydroxyl group. In other embodiments, the substituent is a hydrocarbyloxy group. In other embodiments, the substituent is a carboxyl group. In other embodiments, the substituent is an amine group. In the present invention, "optional" or "optionally" (for example, optionally substituted) means that the subsequent described situation or event may or may not occur, and the description includes examples where the event or situation occurs and examples where the event or situation does not occur. For example, "optionally substituted hydrocarbon group" means that the hydrocarbon group may or may not be substituted, and the description includes substituted hydrocarbon groups and unsubstituted hydrocarbon groups. In the present invention, for a compound or a group, it can be simultaneously substituted and hybridized. For example, a nitro phenyl group substitutes a hydrogen atom, or -CH2-CH2-CH2- is replaced by -CH2-S-CH(CH3)-. In the present invention, the "linking bond" only serves as a connecting function and does not contain any atoms. When a certain group is defined as a linking bond, it means that this group may not exist. In the present invention, a "group" contains at least one atom and refers to a radical formed by a compound losing one or more atoms. A group formed after a compound loses some groups is also called a residue. The valence state of the group is not particularly limited. By way of example, it can be classified into monovalent groups, divalent groups, trivalent groups, tetravalent groups,..., 100-valent groups, etc. Among them, groups with a valence state of 2 or more are collectively called linking groups. A linking group can also contain only one atom, such as an oxygen group or a sulfur group. In the present invention, "hydrocarbon" refers to a hydrocarbon compound composed of carbon atoms and hydrogen atoms. In the present invention, according to the type of hydrocarbon group, hydrocarbons are divided into two types: aliphatic hydrocarbons and aromatic hydrocarbons. A hydrocarbon that does not contain a benzene ring or any structure in a benzene ring substituted by a hydrocarbon group is defined as an aliphatic hydrocarbon. A hydrocarbon that contains at least one benzene ring or a benzene ring substituted by a hydrocarbon group is defined as an aromatic hydrocarbon. And aromatic hydrocarbons can contain an aliphatic hydrocarbon group structure, such as toluene, diphenylmethane, indan, etc. In the present invention, according to the saturation situation, hydrocarbons are divided into two types: saturated hydrocarbons and unsaturated hydrocarbons. All aromatic hydrocarbons are unsaturated hydrocarbons. Saturated aliphatic hydrocarbons are also called alkanes. The degree of unsaturation of unsaturated aliphatic hydrocarbons is not particularly limited. By way of example, it includes but is not limited to alkenes (containing double bonds), alkynes (containing triple bonds), dienes (containing conjugated double bonds), etc. When the aliphatic hydrocarbon part in an aromatic hydrocarbon is a saturated structure, it is also called an arylalkane, such as toluene. In the present invention, there is no particular restriction on the structure of hydrocarbons, which can be in the form of a straight-chain structure without side chains, a branched-chain structure with side chains, a cyclic structure, a dendritic structure, a comb-like structure, a hyperbranched structure, etc. In the absence of a special definition, a straight-chain structure without side chains, a branched-chain structure with side chains, and a cyclic structure are preferably selected, corresponding to straight-chain hydrocarbons, branched-chain hydrocarbons, and cyclic hydrocarbons respectively. Among them, hydrocarbons without a cyclic structure are collectively called open-chain hydrocarbons, including but not limited to a straight-chain structure without side chains and a branched-chain structure with side chains. Open-chain hydrocarbons belong to aliphatic hydrocarbons. Therefore, straight-chain hydrocarbons can also be called straight-chain aliphatic hydrocarbons. Branched-chain hydrocarbons can also be called branched-chain aliphatic hydrocarbons. In the present invention, a "hydrocarbon group" refers to a residue formed after a hydrocarbon loses at least one hydrogen atom. According to the number of hydrogen atoms lost, it can be divided into monovalent hydrocarbon groups (losing one hydrogen atom), divalent hydrocarbon groups (losing two hydrogen atoms, also called sub-hydrocarbon groups), trivalent hydrocarbon groups (losing three hydrogen atoms), etc. By analogy, when losing n hydrogen atoms, the valence state of the formed hydrocarbon group is n. Unless otherwise specifically stated in this specification, the hydrocarbon group in the present invention specifically refers to a monovalent hydrocarbon group. Unless otherwise clearly stated in this specification, the hydrocarbon group is optionally substituted. In the present invention, the source of the hydrocarbon group is not particularly limited. For example, it can be derived from aliphatic hydrocarbons or aromatic hydrocarbons, can also be derived from saturated hydrocarbons or unsaturated hydrocarbons, can also be derived from straight-chain hydrocarbons, branched-chain hydrocarbons or cycloalkanes, and can also be derived from hydrocarbons or heterohydrocarbons, etc. From the perspective of saturation, for example, it can be derived from alkanes, alkenes, alkynes, dienes, etc.; for cycloalkanes, for example, it can be derived from alicyclic hydrocarbons or aromatic hydrocarbons, monocyclic hydrocarbons or polycyclic hydrocarbons; for heterocyclic hydrocarbons, for example, it can be derived from aliphatic heterocyclic hydrocarbons or aromatic heterocyclic hydrocarbons. In the present invention, an "aliphatic hydrocarbon group" refers to a residue formed after an aliphatic hydrocarbon loses at least one hydrogen atom. Without special designation, the aliphatic hydrocarbon group in the present invention specifically refers to a monovalent aliphatic hydrocarbon group. The aliphatic hydrocarbon group includes a saturated aliphatic hydrocarbon group and an unsaturated aliphatic hydrocarbon group. Unless otherwise clearly stated in this specification, the aliphatic hydrocarbon group is optionally substituted. In the present invention, an "alkyl group" refers to a hydrocarbon group formed from an alkane. Without special designation, it refers to a hydrocarbon group formed by losing a hydrogen atom at any position, which can be straight-chain or branched-chain, and can be substituted or unsubstituted. Specifically, for example, propyl refers to any one of n-propyl and isopropyl, and propylene refers to any one of 1,3-propylene, 1,2-propylene, and isopropylene. Unless otherwise clearly stated in this specification, the alkyl group is optionally substituted. In the present invention, an "unsaturated hydrocarbon group" refers to a hydrocarbon group formed after an unsaturated hydrocarbon loses a hydrogen atom. The hydrocarbon group formed after an unsaturated hydrocarbon loses a hydrogen atom on an unsaturated carbon can be classified into alkenyl groups, alkynyl groups, diene groups, etc. In the present invention, an "alkenyl group" refers to a straight-chain or branched-chain hydrocarbon group containing at least one carbon-carbon double bond formed by losing a hydrogen atom at any position of an alkene. For example, "C 2-15 alkenyl" means a straight-chain or branched-chain alkenyl group including 2 to 15 carbon atoms and at least one carbon-carbon double bond, that is, the alkenyl group can include one, two, three, four or more carbon-carbon double bonds. Unless otherwise specifically stated, the alkenyl groups described herein refer to both unsubstituted and substituted alkenyl groups. Unless otherwise clearly stated in this specification, the alkenyl group is optionally substituted. In the present invention, an "alkynyl group" refers to a straight-chain or branched-chain hydrocarbon group containing at least one carbon-carbon triple bond formed by losing a hydrogen atom at any position of an alkyne. For example, "C 2-15 alkynyl" means a straight-chain or branched-chain alkynyl group including 2 to 15 carbon atoms and at least one carbon-carbon triple bond. The alkynyl group can include one, two, three, four or more carbon-carbon triple bonds. Unless otherwise specifically stated, the alkynyl groups described herein refer to both unsubstituted and substituted alkynyl groups. Unless otherwise clearly stated in this specification, the alkynyl group is optionally substituted. In the present invention, a "subhydrocarbon group" or "subhydrocarbon chain" refers to a straight-chain or branched-chain divalent hydrocarbon chain that connects the remaining part of the molecule to a radical group, which consists only of carbon and hydrogen and is saturated or unsaturated. For example, a subhydrocarbon group (C1-24 (alkylene), alkylene having one to twelve carbon atoms (C 1-12 alkylene), specifically, for example, methylene, ethylene, propylene, n-butylene, vinyl, propenyl, n-butenyl, propynyl, n-butynyl, etc. Unless otherwise specifically stated in this specification, the alkylene is optionally substituted. In the present invention, "alkylene" is also a divalent alkyl group, including an open-chain alkylene and a divalent cycloalkyl group. The open-chain alkylene refers to a divalent alkyl group without a cyclic structure, and the divalent cycloalkyl group refers to a divalent alkyl group with a cyclic structure. Unless otherwise specifically stated in this specification, the alkylene is optionally substituted. In the present invention, "molecular weight" characterizes the mass of a compound molecule, and "average molecular weight" characterizes the mass of the components of a general formula compound in a macroscopic substance. When there is no special regulation, the molecular weight of a polymer refers to the "average molecular weight", generally referring to the "number-average molecular weight" M n . For the number-average molecular weight, it can be either the molecular weight of a polydisperse block or substance, or the molecular weight of a monodisperse block or substance. When not specifically stated, the measurement unit of "molecular weight" and "average molecular weight" is Dalton, Da. A polymer can be represented by the "degree of polymerization" indicating the number of repeating units (such as the ethylene oxide unit, EO unit in PEG) in the molecule. Correspondingly, the "average degree of polymerization", "number-average degree of polymerization" or "number of EO units" is used to characterize the average value and number average value of the number of repeating units; when there is no special regulation, it refers to the number-average degree of polymerization. In the present invention, for percentages, "about" generally means ±0.5%. In the present invention, the "stable existence" and "degradability" of a group are a pair of relative concepts. For detailed examples of stable existence groups and degradable groups, see

[0134] -

[0145] section in CN113402405A. In the present invention, "hydroxy protecting group" includes all groups that can be used as the protecting group of a normal hydroxyl group. The hydroxy protecting group is preferably an alkanoyl group (such as acetyl, tert-butylcarbonyl), an aralkanoyl group (such as benzoyl), benzyl, trityl, trimethylsilyl, tert-butyldimethylsilyl, allyl, acetal group or ketal group. The removal of acetyl is generally carried out under alkaline conditions, and the most commonly used are the ammonolysis of NH3 / MeOH and the methanolysis catalyzed by methanol anions; benzyl can be easily removed by palladium-catalyzed hydrogenolysis in a neutral solution at room temperature, and can also be reductively cleaved with metallic sodium in ethanol or liquid ammonia; trityl is generally removed by catalytic hydrogenolysis; trimethylsilyl is usually removed using a fluoride ion-containing reagent (such as tetrabutylammonium fluoride / anhydrous THF, etc.); tert-butyldimethylsilyl ether is relatively stable and can withstand the ester hydrolysis conditions of alcoholic potassium hydroxide and mild reduction conditions (such as Zn / CH3OH, etc.), and can be removed with fluoride ions (such as Bu4N + F- ) It can be removed in a tetrahydrofuran solution or with acetic acid containing water at room temperature. In the present invention, the "carboxyl protecting group" refers to a protecting group that can be converted into a carboxyl group through hydrolysis or a deprotection reaction of the carboxyl protecting group. The carboxyl protecting group is preferably an alkyl group (such as methyl, ethyl, tert-butyl) or an aralkyl group (such as benzyl), more preferably tert-butyl (tBu), methyl (Me) or ethyl (Et). In the present invention, the "protected carboxyl group" refers to a group formed after the carboxyl group is protected by a suitable carboxyl protecting group, preferably methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, benzyloxycarbonyl. The carboxyl protecting group can be removed by hydrolysis under the catalysis of an acid or a base, and occasionally can also be removed by a pyrolysis reaction. For example, tert-butyl can be removed under mild acidic conditions, and benzyl can be removed by hydrogenolysis. The reagent for removing the carboxyl protecting group is selected from TFA, H2O, LiOH, NaOH, KOH, MeOH, EtOH and their combinations, preferably the combination of TFA and H2O, the combination of LiOH and MeOH, or the combination of LiOH and EtOH. The protected carboxyl group is deprotected to produce the corresponding free acid, and the deprotection is carried out in the presence of a base, and the base and the free acid formed by the deprotection form a pharmaceutically acceptable salt. In the present invention, the "amino protecting group" includes all groups that can be used as the protecting group of a normal amino group, such as aryl C 1-6 alkyl, C 1-6 alkoxy C 1-6 alkyl, C 1-6 alkoxycarbonyl, aryloxycarbonyl, C 1-6 alkylsulfonyl, arylsulfonyl or silyl, etc. The amino protecting group is preferably Boc tert-butoxycarbonyl, Moz p-methoxybenzyloxycarbonyl or Fmoc 9-fluorenylmethyloxycarbonyl. The reagent for removing the amino protecting group is selected from TFA, H2O, LiOH, MeOH, EtOH and their combinations, preferably the combination of TFA and H2O, the combination of LiOH and MeOH, or the combination of LiOH and EtOH. The reagent for removing the Boc protecting group is TFA or HCl / EA; preferably TFA. The deprotecting agent used for the reaction of removing the Fmoc protecting group is a solution of N,N-dimethylformamide (DMF) containing 20% piperidine. In the present invention, "cationic lipid" refers to a lipid that contains a net positive charge or an ionizable lipid. Among them, "cationic" means that the corresponding structure permanently or non-permanently carries a positive charge in response to certain conditions (such as pH). Therefore, cations include both permanent cations and cationizable ones. A permanent cation means that the corresponding compound, group or atom carries a positive charge at any pH value or hydrogen ion activity in its environment. Typically, a positive charge is generated due to the presence of a quaternary ammonium atom. When a compound carries multiple such positive charges, it can be called a permanent cation. Cationizable means that a compound, group or atom carries a positive charge at a lower pH and does not carry a charge at a higher pH in its environment. Additionally, in a non-aqueous environment where the pH value cannot be measured, a cationizable compound, group or atom carries a positive charge at a high hydrogen ion concentration and does not carry a charge at a low hydrogen ion concentration or activity. It depends on the individual properties of the cationizable or polycationizable compound, especially the pKa of the corresponding cationizable group or atom, at which it carries a charge or does not carry a charge at the said pH or hydrogen ion concentration. In a dilute aqueous environment, the so-called Henderson-Hasselbalch equation can be used to estimate the fraction of the cationizable compound, group or atom carrying a positive charge, which is well-known to those skilled in the art. For example, in some embodiments, if a compound or moiety is cationizable, preferably, it carries a positive charge at a pH value of about 1 to 9, preferably 4 to 9, 5 to 8 or even 6 to 8, more preferably at a pH value equal to or lower than 9, equal to or lower than 8, equal to or lower than 7, and most preferably at a physiological pH value (such as about 7.3 to 7.4), that is, under physiological conditions, especially under the physiological conditions of cells in vivo. In other embodiments, preferably, the cationizable compound or moiety is mainly neutral at a physiological pH value (such as about 7.0 - 7.4), but becomes positively charged at a lower pH value. In some embodiments, the preferred range of the pKa of the cationizable compound or moiety is about 5 to about 7. In the present invention, lipid nanoparticles, cationic peptides, proteins, polysaccharides, lipids or polymers are uncharged, have a neutral charge or are electrically neutral under physiological conditions, especially under the physiological conditions of cells in vivo. The cationic peptide or protein preferably contains a relatively large amount of cationic amino acids, such as Arg, His, Lys or Orn in a larger number than other amino acid residues (especially more cationic amino acids than anionic amino acid residues such as Asp or Glu), or contains a component mainly formed by cationic amino acid residues. The term "cationic" can also refer to a "poly-cationic" component / cationic component / compound, and can also refer to a cationic lipid capable of carrying a positive charge. For example, a cationic lipid contains one or more amine groups with a positive charge, and the preferred cationic lipid is ionizable so that they can exist in a positively charged form or a neutral form according to the pH. The ionization of the cationic lipid affects the surface charge of the lipid nanoparticle (LNP) under different pH conditions. This charge state can affect plasma protein absorption, blood clearance and tissue distribution, as well as the ability to form a non-bilayer structure crucial for intracellular delivery of nucleic acids. In the present invention, "PEGylated lipid" refers to a molecule containing a lipid moiety and a polyethylene glycol moiety. In the present invention, "neutral lipid" refers to any of many lipid substances that exist in an uncharged or neutral zwitterionic form at a selected pH, preferably a phospholipid, which can be synthetic or of natural origin. In the present invention, "steroid lipid" is a steroid or a steroid analogue. In the present invention, "amino acid residue" includes an amino acid from which a hydrogen atom is removed from the amino group and / or a hydroxyl group is removed from the carboxyl group and / or a hydrogen atom is removed from the mercapto group and / or the amino group is protected and / or the carboxyl group is protected and / or the mercapto group is protected. Loosely speaking, an amino acid residue can be called an amino acid. The source of the amino acid in the present invention is not particularly limited without special indication, and can be either a natural source, a non-natural source, or a mixture of both. The structural type of the amino acid in the present invention is not particularly limited without special indication, and can refer to the L-type, the D-type, or a mixture of both. In another embodiment of the present invention, the amino acid is a hydrophilic amino acid selected from any one of glutamic acid (Glu) and aspartic acid (Asp). The variant in the present invention refers to a structural form that can be transformed into a target reactive group through any one of chemical change processes such as oxidation, reduction, hydration, dehydration, electron rearrangement, structural rearrangement, salt complexation and dissociation, ionization, protonation, deprotonation, substitution, deprotection, and change of leaving group. In the present invention, the "variant form of a reactive group" refers to a form that remains active (is still a reactive group) after undergoing at least one chemical change process such as oxidation, reduction, hydration, dehydration, electronic rearrangement, structural rearrangement, salt complexation and dissociation, ionization, protonation, deprotonation, substitution, deprotection, or change of a leaving group, or a non-active form after being protected. In the present invention, "any suitable linker", "any suitable reactive group", etc., the "any suitable" means a structure that conforms to the basic principles of chemical structure and enables the smooth implementation of the preparation method of the present invention. The chemical structure described in this way can be regarded as having a clear and definite scope. In the present invention, when at least two structural types are listed, the "any combination" of the listed structural types refers to the combination of any two or more of the aforementioned related structural types; and there is no limitation on the number of structural units. The number of any one structural unit can be zero, one, or more than one. When the number of the same type of structural units is more than 1, they can be structural units with the same or different chemical structures, and the total number of constituent units is at least 2. For example, examples of any combination of alkylene, divalent cycloalkyl, divalent cycloalkenyl, divalent cycloalkynyl, divalent cyclo-dienyl, arylene, carbon-carbon double bond, carbon-carbon triple bond, conjugated carbon-carbon double bond, divalent heteroatom-containing aliphatic ring linker, divalent heteroatom-containing aromatic ring linker, and carbon chain linker with a heteroatom in the side chain include -Ph-CH2-Ph- (arylene-alkylene-arylene), -CH2-Ph-CH2CH2- (alkylene-arylene-alkylene, where the number of alkylene is 2 and has different chemical structures), or the benzene ring in the aforementioned examples is replaced with a cyclohexane ring, a diazahexane ring, or the structure of 1-(2-pyridyl)hexahydro-1H-1,4-diazepine. Another example is that cycloalkenyl hydrocarbon group = cycloalkenyl + alkylene group = cycloalkenyl as a substituent of the hydrocarbon group, and cyclo-dienyl hydrocarbon group = cyclo-dienyl as a substituent of the hydrocarbon group. In the present invention, the "N / P ratio" refers to the molar ratio of nitrogen atoms in the cationic lipid to phosphoric acid in the nucleic acid. In the present invention, "nucleic acid" refers to DNA or RNA or a modified form thereof, which contains purine or pyrimidine bases present in DNA (adenine "A", cytosine "C", guanine "G", thymine "T") or purine or pyrimidine bases present in RNA (adenine "A", cytosine "C", guanine "G", uracil "U"). In the present invention, "RNA" refers to ribonucleic acid that may be naturally occurring or non-naturally occurring. For example, RNA may include modified and / or non-naturally occurring components, such as one or more nucleobases, nucleosides, nucleotides, or linkers. RNA may include a cap structure, a chain-terminating nucleoside, a stem-loop, a polyadenylation sequence, and / or a polyadenylation signal. RNA may be a nucleotide sequence encoding a specific polypeptide and may be messenger RNA (mRNA). Translating the mRNA encoding a specific polypeptide, for example, translating the mRNA in vivo inside mammalian cells can produce the encoded polypeptide. RNA may be selected from any of the following: small interfering RNA (siRNA), asymmetric interfering RNA (aiRNA), microRNA (miRNA), Dicer-substrate RNA (dsRNA), short hairpin RNA (shRNA), mRNA, single-stranded guide RNA (sgRNA), self-amplifying RNA (saran), circular RNA (circRNA), cas9 mRNA, and mixtures thereof. In the present invention, an antisense oligonucleotide or small interfering RNA (siRNA) can inhibit the expression of a target gene and a target protein in vitro or in vivo. In the present invention, FLuc mRNA can express luciferase protein, which emits bioluminescence in the presence of a luciferin substrate, so FLuc is commonly used in mammalian cell culture to measure gene expression and cell viability. In the present invention, "inhibiting the expression of a target gene" refers to the ability of a nucleic acid to silence, reduce, or inhibit the expression of a target gene. To test the degree of gene silencing, a test sample (e.g., a cell sample in a culture medium expressing the target gene) is contacted with a nucleic acid that inhibits the expression of the target gene. The expression of the target gene in the test sample or test animal is compared with the expression of the target gene in a control sample (e.g., a cell sample in a culture medium expressing the target gene) that has not been contacted or administered the nucleic acid. The expression of the target gene in the control sample may be designated as a value of 100%. In a particular embodiment, when the expression level of the target gene in the test sample is about 95%, 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, 50%, 45%, 40%, 35%, 30%, 25%, 20%, 15%, 10%, 5%, or 0% relative to the expression level of the target gene in the control sample or control mammal, the inhibition of the expression of the target gene is achieved. In the present invention, methods for determining the expression level of a target gene include, but are not limited to, dot blot, northern blot, in situ hybridization, ELISA, immunoprecipitation, enzymatic action, and phenotypic assays. In the present invention, "transfection" refers to the introduction of a species (e.g., RNA) into a cell. Transfection can occur, for example, in vitro, ex vivo, or in vivo. In the present invention, an "antigen" typically refers to a substance that can be recognized by the immune system, preferably by the adaptive immune system, and is capable of triggering an antigen-specific immune response, such as by forming antibodies and / or antigen-specific T cells as part of the adaptive immune response. Typically, an antigen can be or can comprise a peptide or protein that can be presented by MHC to T cells. In the context of the present invention, an antigen can be the translation product of the provided nucleic acid molecule (preferably mRNA as defined herein). In this context, fragments, variants, and derivatives of peptides and proteins that contain at least one epitope are also understood as antigens. In the present invention, "delivery" refers to providing an entity to a target. For example, delivering a drug and / or therapeutic agent and / or prophylactic agent to a subject, which is a tissue and / or cell of a human and / or other animal. In the present invention, a "pharmaceutically acceptable carrier" refers to a diluent, adjuvant, excipient or vehicle administered together with a therapeutic agent, and is suitable, within the scope of reasonable medical judgment, for contact with the tissues of humans and / or other animals without excessive toxicity, irritation, allergic response or other problems or complications commensurate with a reasonable benefit / risk ratio. Pharmaceutically acceptable carriers that can be used in the pharmaceutical compositions of the present invention include, but are not limited to, sterile liquids such as water and oils, including those of petroleum, animal, vegetable or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil, etc. When the pharmaceutical composition is administered intravenously, water is an exemplary carrier. Physiological saline and aqueous solutions of glucose and glycerol can also be used as liquid carriers, especially for injection solutions. Suitable pharmaceutical excipients include starch, glucose, lactose, sucrose, gelatin, maltose, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, skim milk powder, glycerol, propylene glycol, water, ethanol, etc. The composition may also optionally contain small amounts of wetting agents, emulsifying agents or pH buffering agents. Oral formulations may contain standard carriers such as pharmaceutical grade mannitol, lactose, starch, magnesium stearate, saccharin sodium, cellulose, magnesium carbonate, etc. Specifically, for example, excipients include, but are not limited to, anti-adhesion agents, antioxidants, binders, coatings, compression aids, disintegrants, dyes (pigments), demulcents, emulsifying agents, fillers (diluents), film formers or coatings, flavoring agents, fragrances, glidants (flow enhancers), lubricants, preservatives, printing inks, adsorbents, suspending or dispersing agents, sweetening agents, and water for hydration. More specifically, excipients include, but are not limited to, butylated hydroxytoluene (BHT), calcium carbonate, dibasic calcium phosphate, calcium stearate, croscarmellose sodium, crospovidone, citric acid, crospovidone, cysteine, ethyl cellulose, gelatin, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, lactose, magnesium stearate, maltitol, mannitol, methionine, methyl cellulose, methylparaben, microcrystalline cellulose, polyethylene glycol, polyvinylpyrrolidone, povidone, pregelatinized starch, phenylparaben, retinyl palmitate, shellac, silica, sodium carboxymethyl cellulose, sodium citrate, sodium starch glycolate, sorbitol, starch (corn), stearic acid, sucrose, talc, titanium dioxide, vitamin A, vitamin E (α-tocopherol), vitamin C, xylitol. In the present invention, a vaccine is a prophylactic or therapeutic material that provides at least one antigen or antigen function. The antigen or antigen function can stimulate the adaptive immune system of the body to provide an adaptive immune response. In the present invention, "treatment" refers to the treatment and care of a patient for the purpose of combating a disease, disorder or condition, and is intended to include delaying the progression of the disease, disorder or condition, alleviating or mitigating symptoms and complications, and / or curing or eliminating the disease, disorder or condition. The patient to be treated is preferably a mammal, especially a human. 1. Cationic lipid One embodiment of the present invention: A cationic lipid, characterized in that the structure is as shown in the general formula (1): Or its salt, tautomer, stereoisomer, deuterated compound or solvate; Wherein, Core is a nitrogen-containing heterocyclic nucleus; L is a divalent linking group L d , said L d is selected from -(CH2) tm -, -Z-, -(CH2) tm Z-, -Z(CH2) tm -, -Z(CH2) tm Z-, -(CH2) tm Z(CH2) tm -, -Z(CH2) tm Z(CH2) tm -, -(CH2) tm Z(CH2) tm Z- and -(CH2) tm Z(CH2) tm Z(CH2) tm - any one of them, wherein, tm is independently an integer from 1 to 12 each time it appears; Z is independently -C(=O)-, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -O-, -S-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -, -NR c C(=O)NR c -, -OC(=O)NR c -, -NR c C(=O)O-, -SC(=O)NR c -, and -NR c C(=O)S- any one of them, wherein, R c is independently H or C 1-12 alkyl each time it appears; AA is a residue of aspartic acid, glutamic acid or the aforementioned amino acid derivative; B1 and B2 are each independently a linking bond or C 1-20 alkylene each time they appear; L1, L2, L3, and L4 are each independently a linking bond or a divalent linking group L a ; said L aSelected from -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -NH-, -O(CH2) s O-, -S-, -S-S-, -C(=O)S-, -SC(=O)-, -NHC(=O)-, -C(=O)NH-, -NHC(=O)NH-, -OC(=O)NH-, -NR c C(=O)O-, -SC(=O)NH-, -NHC(=O)S-, -C(=S)-, -OC(=S)-, -C(=S)O-, -OC(=S)O-, -NHC(=S)-, -C(=S)NH-, -NHC(=S)NH-, -OC(=S)NH- and -NHC(=S)O-, where s is 1, 2, 3 or 4; L1 and L3 are not both a linking bond at the same time; L2 and L4 are not both a linking bond at the same time; Each occurrence of R1 and R2 is independently a C 5-30 hydrocarbyl group or a C 5-30 hydrocarbyl derivative; a and b are each independently 1 or 2; when the -B1-L1-R1 and / or -B2-L2-R2 fragment is derived from the amino terminus of an amino acid and its derivatives, a and b are each independently 1 or 2; when the -B1-L1-R1 and / or -B2-L2-R2 fragment is derived from the carboxyl terminus of an amino acid and its derivatives, a and b are each independently 1; when a and b are 2, the two -B1-L1-R1 and / or -B2-L2-R2 fragments are each independently the same or different; c is 2, 3 or 4. 1.1.Core In the present invention, Core is a nitrogen-containing heterocyclic nucleus. In a specific embodiment of the present invention, the aforementioned Core is where n is 1 or 2; preferably Core is Most preferably it is 1.2.L In the present invention, L is a divalent linking group L d . In a specific embodiment of the present invention, the L is -(CH2) tm -, -(CH2) tm O-, -(CH2) tm C(=O)-, -(CH2) tm C(=O)O-, -(CH2) tm OC(=O)-, -(CH2) tm C(=O)NH-, -(CH2)tm NHC(=O)-, -(CH2) tm OC(=O)O-, -(CH2) tm NHC(=O)O-, -(CH2) tm OC(=O)NH-, -(CH2) tm NHC(=O)NH-, -C(=O)(CH2) tm C(=O)-, -C(=O)(CH2) tm C(=O)(CH2) tm -, -(CH2) tm O(CH2) tm -, -(CH2) tm C(=O)(CH2) tm -, -(CH2) tm C(=O)O(CH2) tm -, -(CH2) tm OC(=O)(CH2) tm -, -(CH2) tm C(=O)NH(CH2) tm -, -(CH2) tm NHC(=O)(CH2) tm -, -(CH2) tm OC(=O)O(CH2) tm -, -(CH2) tm NHC(=O)O(CH2) tm -, -(CH2) tm C(=O)O(CH2) tm O(CH2) tm -, -(CH2) tm NH-, -(CH2) tm O(CH2) tm NH-, -(CH2) tm OC(=O)NH(CH2) tm - and -(CH2) tm NHC(=O)NH(CH2) tm any one of -, and the left end is connected to a nitrogen-containing heterocycle; preferably -(CH2) tm O-, -(CH2) tm NH-, -(CH2) tm C(=O)-, -(CH2) tm O(CH2) tm -, -(CH2) tm C(=O)O(CH2) tm -, -(CH2) tmOC(=O)(CH2) tm -, -(CH2) tm O(CH2) tm NH-, -(CH2) tm NHC(=O)(CH2) tm -, -(CH2) tm C(=O)O(CH2) tm O(CH2) tm Any one of -; preferably, L is any one of -CH2C(=O)-, -CH2C(=O)O(CH2)4-, -CH2C(=O)O(CH2)3-, -CH2C(=O)O(CH2)2O(CH2)2-, -(CH2)2O-, -(CH2)2NH-, -(CH2)2NHC(=O)(CH2)3-, -(CH2)2OC(=O)(CH2)3- and -(CH2)2O(CH2)2NH-, and the left end is connected to the nitrogen-containing heterocycle. 1.3.AA In the present invention, AA is a residue of aspartic acid, glutamic acid or the aforementioned amino acid derivatives. In a specific embodiment of the present invention, the AA is wherein, R a is independently a linking bond, H or C 1-6 alkyl each time it appears, and the C 1-6 alkyl is preferably methyl, ethyl, propyl or isopropyl; t3 is 0 or 1; Or AA is in the case where one or two carbonyl groups are each independently capped with an oxygen atom or a secondary amine atom, and is selected from any one of the following structures: More preferably, AA is any one of the following structures: wherein, R a is C 1-6 alkyl; Most preferably, AA is 1.4.B1, B2 In the present invention, B1 and B2 are each independently a linking bond or C 1-20 alkylene. In a specific embodiment of the present invention, the B1 and B2 are any one of the following cases: Case (1): B1 and B2 are each independently C 1-20An alkylene group, more preferably, each of B1 and B2 is independently a C 2-10 alkylene group; the C 2-10 alkylene group is preferably any one of ethylene, propylene, butylene, pentylene, hexylene, heptylene, and octylene; Case (2): One of B1 and B2 is a linking bond, and the other is a C 1-20 alkylene group; Case (3): Both B1 and B2 are linking bonds; More preferably, B1 and B2 are selected from the aforementioned case (1) or case (3). 1.5. L1, L2 In the present invention, each occurrence of L1 and L2 is independently a linking bond or a divalent linking group L a , the L a is selected from -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -NH-, -O(CH2) s O-, -S-, -S-S-, -C(=O)S-, -SC(=O)-, -NHC(=O)-, -C(=O)NH-, -NHC(=O)NH-, -OC(=O)NH-, -NHC(=O)O-, -SC(=O)NH-, -NHC(=O)S-, -C(=S)-, -OC(=S)-, -C(=S)O-, -OC(=S)O-, -NHC(=S)-, -C(=S)NH-, -NHC(=S)NH-, -OC(=S)NH-, and -NHC(=S)O-; where s is 1, 2, 3, or 4. In a specific embodiment of the present invention, L1 and L2 are any one of the following cases: Case (1): L1 and L2 are each independently selected from L a ; Case (2): One of L1 and L2 is a linking bond, and the other is L a ; Case (3): Both L1 and L2 are linking bonds; Preferably, L1 and L2 are each independently a linking bond, -C(=O)-, -O-, -NH-, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -OC(=O)NH-, -NHC(=O)O-, -NHC(=O)-, and -C(=O)NH-; More preferably, L1 and L2 are the same and are both a linking bond, -O-, -NH-, -OC(=O)-, or -C(=O)O-. 1.6. L3, L4 In the present invention, each occurrence of L3 and L4 is independently a linking bond or a divalent linking group L a . In a specific embodiment of the present invention, each occurrence of L3 and L4 is independently any one of a linking bond, -O-, -NH-, -C(=O)-, and -C(=O)O-; preferably, one of L3 and L4 is a linking bond, and the other is -O-, -NH-, -C(=O)-, -C(=O)O-; more preferably, L3 and L4 are the same and are selected from any one of a linking bond, -O-, and -NH-. 1.7.R1, R2 In the present invention, R1 and R2 are each independently a C 5-30 linear hydrocarbon group, a C 5-30 branched hydrocarbon group, or a C 5-30 hydrocarbon group derivative, and the C 5-30 hydrocarbon group derivative is represented as The linear hydrocarbon group and the branched hydrocarbon group are each independently substituted or unsubstituted, and the substitution is preferably by a C 1-6 alkyl group, a halogen, or a hydroxyl group. In a specific embodiment of the present invention, the linear hydrocarbon group is a linear alkyl group, a linear alkenyl group, or a linear alkynyl group; more preferably, it is a C 5-25 linear hydrocarbon group. In a specific embodiment of the present invention, the branched hydrocarbon group is a branched alkyl group, a branched alkenyl group, or a branched alkynyl group, and each independently is represented as Among the aforementioned R1 and R2, t is an integer from 0 to 12, t1 and t2 are each independently an integer from 0 to 5, t3 and t4 are each independently 0 or 1, and t1, t2, t3, and t4 are not simultaneously 0; R e , R f are each independently a C 1-15 alkyl group, a C 2-15 alkenyl group, and a C 2-15 alkynyl group; R e , R f are more preferably each independently selected from any one of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, vinyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl, nonenyl, decenyl, ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl, nonynyl, and decynyl; R e , R f are more preferably each independently selected from any one of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, and decyl. In a specific embodiment of the present invention, R1 and R2 are preferably any one of the following cases: Case (1): R1 and R2 are each independently C 5-30 linear hydrocarbon group; Case (2): One of R1 and R2 is C 5-30 linear hydrocarbon group, and the other is C 5-30 branched hydrocarbon group Case (3): R1 and R2 are each independently C 5-30 branched hydrocarbon group Case (4): R1 and R2 are each independently Case (5): One of R1 and R2 is C 5-30 linear hydrocarbon group or C 5-30 branched hydrocarbon group and the other is In a more specific embodiment of the present invention, R1 and R2 satisfying the above cases are further preferably each independently selected from any one of the following structures: 1,8 - B1 - L1 - R1 and - B2 - L2 - R2 fragments In a specific embodiment of the present invention, each occurrence of the - B1 - L1 - R1 and - B2 - L2 - R2 fragments is independently selected from any one of the following structures: 1.9. Examples of structural formulas In a specific embodiment of the present invention, according to the Core described in 1.1 and the AA described in 1.3, the structure of the cationic lipid of the present invention is selected from any one of the following general formulas: wherein, t3 is 0 or 1; R a is H or C 1-6 alkyl; L1, L2, L3, L4, B1, B2 are not all linker bonds; the definitions of the other symbols are the same as those in formula (1); Preferably, L in formula (2 - A), formula (2 - B), and formula (2 - C) is -(CH2) tm Z(CH2) tm - or -(CH2) tm Z(CH2) tm Z(CH2) tm-, wherein each occurrence of Z is independently any one of -OC(=O)-, -C(=O)O-, -OC(=O)O-, -NHC(=O)-, -C(=O)NH-, -NHC(=O)O-, -OC(=O)NH-, -O-, -NH-, and L is more preferably -(CH2) tm O-, -(CH2) tm NH-, -(CH2) tm C(=O)-, -(CH2) tm O(CH2) tm -, -(CH2) tm C(=O)O(CH2) tm -, -(CH2) tm OC(=O)(CH2) tm -, -(CH2) tm O(CH2) tm NH-, -(CH2) tm NHC(=O)(CH2) tm -, -(CH2) tm C(=O)O(CH2) tm O(CH2) tm -; In a specific embodiment of the present invention, the structure of the aforementioned cationic lipid preferably satisfies any one of the following general formulas: Wherein, * represents the same structure as in [], and Z in formulas (3-1) to (3-24) is -C(=O)O-, -OC(=O)-, -C(=O)NH-, -NHC(=O)-, -OC(=O)NH- or -NHC(=O)O-; In all of the aforementioned general formulas, it is preferred that L1 and L2 are each independently any one of -C(=O)-, -O-, -NH-, -C(=O)O-, -OC(=O)-, -OC(=O)O-, -C(=O)NH-, -NHC(=O)-, -OC(=O)NH-, -NHC(=O)O-; more preferably, L1 and L2 are each independently any one of -O-, -NH-, -C(=O)-, -C(=O)O-, -OC(=O)-, -OC(=O)O-; More preferably, the structure of the cationic lipid satisfies any one of formulas (3-1) to (3-6), where Z is -C(=O)O-, -OC(=O)-, -C(=O)NH-, or -NHC(=O)-; L1 and L2 are each independently any one of -O-, -NH-, -C(=O)O-, -OC(=O)-, -OC(=O)O-; L3 and L4 are each independently -O- or -NH-. 1.10. Specific structural examples In one embodiment of the present invention, the structure of the preferred cationic lipid is selected from any one of the following structures: Or the structure of the cationic lipid is any one of the following structures: Or the structure of the cationic lipid is any one of the following structures: Or the structure of the cationic lipid is any one of the following structures: Or the structure of the cationic lipid is any one of the following structures: 2. Preparation of cationic lipids 2.1. The intermediates / raw materials involved in the preparation process of the present invention include but are not limited to CORE0, IM-N, IM-AA’, IM-AA, and CORE-AA’. The preparation process of the present invention may involve an initial raw material CORE0 containing a nitrogen-containing heterocyclic nucleus, where CORE0 contains c identical functional groups F0, and F0 is preferably protected or unprotected -OH, -COOH, -NH2, -NH-, -Br, and c is 2, 3, or 4. CORE0 can be obtained by purchase or by further modification of a nitrogen-containing heterocyclic compound, and the modification refers to preparation by any suitable single-step or multi-step chemical reaction. For example, in Example 1, S1-1 and S1-2 CORE0 can be obtained through substitution reaction In the present invention, CORE0 is selected from any one of the following structures: In the preparation process of the present invention, it may involve a small molecule intermediate IM-N containing a reactive group and a hydrophobic hydrocarbon tail chain, and its structure is represented as F C -B1-L1-R1, F C -B2-L2-R2, where F C is a group capable of reacting with the end group of an amino acid or an amino acid derivative, preferably protected or unprotected -OH, protected or unprotected -NH2, and the definitions of the other symbols are the same as those described in the general formula (1). IM-N can be obtained by purchase or prepared through any suitable chemical reaction, and the any suitable chemical reaction includes single-step or multi-step reactions such as simple esterification, amidation, alkylation, addition or substitution. For example, in Example 2, S2-1 and S2-2 A small molecule intermediate IM-N can be obtained through a condensation reaction followed by removal of the TBS protecting group In the present invention, the structure of the aforementioned IM-N is preferably F C -R1, F C -R2, F C -L1-R1, F C -L2-R2, F C -B1-L1-R1, F C -B2-L2-R2, and specifically, more preferably IM-N is selected from any one of the following structures: In the preparation process of the present invention, it may involve an intermediate IM-AA' containing a reactive amino acid end group and at least two hydrophobic hydrocarbon tail chains, and its structure is represented as where AA' contains a reactive amino acid end group, and the definitions of the other symbols are the same as those described in the general formula (1). IM-AA' can be obtained by performing single-step or multi-step identical or different hydrophobic hydrocarbon tail chain modifications on an amino acid or its derivative. For example, in Example 1, S1-4 and S1-5 A small molecule intermediate IM-AA' can be obtained through a condensation reaction followed by removal of the Boc protecting group In the present invention, the structure of the aforementioned IM-AA' is preferably any one of them. Specifically, more preferably, IM-AA' is selected from any one of the following structures: The preparation process of the present invention may involve an intermediate IM-AA containing one amino acid residue and at least two hydrophobic hydrocarbon chains, and the structure is represented as wherein, L n is any suitable divalent linking group, F2 is a reactive group capable of reacting with F0 of CORE0, and the definitions of the other symbols are the same as those described in the general formula (1). IM-AA can be obtained by functionalizing the amino acid end group that can react with IM-AA'. In the present invention, the structure of the aforementioned IM-AA is preferably any one of them. Specifically, more preferably, IM-AA is selected from any one of the following structures: The preparation process of the present invention may involve an intermediate CORE-AA' containing a nitrogen-containing heterocycle, and the structure is represented as wherein, AA' contains two identical or different reactive amino acid end groups, and the definitions of the other symbols are the same as those described in the general formula (1). CORE-AA' can be obtained by reacting CORE0 with an amino acid or its derivative in one or more identical or different steps. In the present invention, preferably, CORE-AA' is selected from any one of the following structures: In the present invention, the cationic lipid can be prepared by reacting any one of the aforementioned CORE0 with any one of IM-AA' or IM-AA; it can also be obtained by reacting any one of the aforementioned CORE-AA' with any one of IM-N. 2.2. Description of related raw materials and / or steps in the preparation process 2.2.1. Condensing agent, oxidizing agent, reducing agent In the present invention, the condensing agent used in the reaction is not limited, but N,N'-diisopropylcarbodiimide (DIC), N,N'-dicyclohexylcarbodiimide (DCC), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl, EDCI), 2-(7-azabenzotriazol)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU), benzotriazol-N,N,N',N'-tetramethyluronium hexafluorophosphate (HBTU) are preferred, and DCC is most preferred. An appropriate catalyst (such as 4-dimethylaminopyridine) can be added to this reaction. In the present invention, the oxidizing agent used in the reaction is not particularly limited, as long as it is a compound or a combination of multiple compounds that can increase the valence of the substrate. Preferred are phenyl iodide bis(trifluoroacetate), 1,4-benzoquinone, benzyltrimethylammonium tribromide, pyridinium dichromate, potassium dichromate, ozone, oxygen, hypofluorous acid, sodium hypochlorite, cobalt(III) acetate, cobalt(II) acetate, manganese(II) acetate, palladium(II) acetate, copper(II) acetate, monoperoxyphthalic acid, iodine, N-iodosuccinimide, iodobenzene, 2-iodoxybenzoic acid, dimethyldioxirane, dimethyl sulfoxide-oxalyl chloride, dimethyl sulfoxide-acetic anhydride, DDQ, dichloro(tris(triphenylphosphine))ruthenium, manganese dioxide, diacetoxyiodobenzene, periodic acid, sodium periodate, sodium periodate-osmium tetroxide, potassium permanganate, sodium metaborate, peroxybenzoic acid, benzoyl peroxide, nickel peroxide, hydrogen peroxide, cumene hydroperoxide, tert-butyl hydroperoxide, peracetic acid, m-chloroperoxybenzoic acid, N-chlorosuccinimide, pyridinium chlorochromate, palladium(II) chloride-copper(II) chloride, urea hydrogen peroxide complex, triphenylmethyl tetrafluoroborate, tributyltin oxide, cobalt(III) fluoride, vanadyl trifluoride, chromium(III) oxide, manganese(III) acetate, TEMPO, ammonium cerium(IV) nitrate, bromine, N-oxidopyridine, silver oxide, O-ethyl peroxycarbonate, manganese(II) acetylacetonate, vanadyl acetylacetonate, aluminum isopropoxide, potassium peroxymonosulfate, dichloroiodobenzene, etc., or a combination thereof. More preferred is a combination of one or more of oxygen, sodium hypochlorite, hydrogen peroxide, dichloroiodobenzene, potassium peroxymonosulfate, etc. In the present invention, the reducing agent used in the reaction is not particularly limited, as long as it can reduce the Schiff base formed by ammonia and aldehyde or ketone to an amino group; preferred are sodium borohydride, sodium cyanoborohydride, lithium aluminum hydride, borane, diborane, diisobutylaluminum hydride, diisopinocampheylborane, lithium borohydride, zinc borohydride, borane-pyridine, borane-methyl sulfide, borane-tetrahydrofuran, etc., or a combination thereof; more preferred is sodium cyanoborohydride. In the present invention, the solvent for the reaction can be a solvent-free or aprotic solvent. Aprotic solvents include toluene, benzene, xylene, acetonitrile, ethyl acetate, diethyl ether, methyl tert-butyl ether, tetrahydrofuran, chloroform, dichloromethane, dimethyl sulfoxide, dimethylformamide or dimethylacetamide. Preferred are tetrahydrofuran, dichloromethane, dimethyl sulfoxide, dimethylformamide. In the present invention, the base used in the reaction is an inorganic base or an organic base, preferably an organic base (such as triethylamine, pyridine, 4-dimethylaminopyridine, imidazole or diisopropylethylamine); preferably triethylamine and pyridine. 2.2.2. "Protection" and "deprotection" of related groups involved in the reaction process In the present invention, there are "protection" and "deprotection" processes of related groups involved in the reaction process. To prevent the functional group from affecting the reaction, the functional group is usually protected. Moreover, when there are two or more functional groups, only the target functional group is selectively made to react, so other functional groups are protected. The protecting group not only stably protects the target functional group, but also needs to be easily removed as needed. Therefore, in organic synthesis, it is important to deprotect only the protecting group bonded to the specified functional group under appropriate conditions. In the present invention, the definitions of "carboxyl protecting group" and "amino protecting group" are the same as those in the "Term Explanation" section, and will not be elaborated here. In the present invention, the hydroxyl group protected by the hydroxyl protecting group is not particularly limited. For example, it can be a hydroxyl group such as an alcohol hydroxyl group or a phenolic hydroxyl group. Among them, the amino group of the amino protecting group is not particularly limited. For example, it can come from a primary amine, a secondary amine, a hydrazine, an amide, etc. The amino group in the present invention is not particularly limited, including but not limited to a primary amino group, a secondary amino group, a tertiary amino group, and a quaternary ammonium ion. In the present invention, the deprotection of the protected hydroxyl group is related to the type of the hydroxyl protecting group. The type of the hydroxyl protecting group is not particularly limited. Taking the protection of the terminal hydroxyl group with a benzyl group, a silyl ether, or a tert-butyl group as an example, the corresponding deprotection methods are as follows: A: Deprotection of the benzyl protecting group The deprotection of the benzyl group can be achieved by the hydrogenation of a hydrogenation reducing agent and a hydrogen donor. The water content in this reaction system should be less than 1% for the reaction to proceed smoothly. The hydrogenation reduction catalyst is not limited. Palladium and nickel are preferred, but the carrier is not limited. However, alumina or carbon is preferred, and carbon is more preferred. The dosage of palladium is 1 to 100 wt% of the compound containing the protected hydroxyl group, preferably 1 to 20 wt% of the compound containing the protected hydroxyl group. The reaction solvent is not particularly limited as long as both the raw materials and the products can be dissolved. However, methanol, ethanol, ethyl acetate, tetrahydrofuran, and acetic acid are preferred; methanol is more preferred. The hydrogen donor is not particularly limited, but hydrogen, cyclohexene, 2-propanol, ammonium formate, etc. are preferred. The reaction temperature is preferably 25 to 40 °C. The reaction time is not particularly limited. The reaction time is negatively correlated with the dosage of the catalyst, and is preferably 1 to 5 hours. B: Deprotection of the silyl ether protecting group Compounds used for such hydroxyl protection include trimethylsilyl ether, triethylsilyl ether, dimethyl tert-butylsilyl ether, tert-butyldiphenylsilyl ether, etc. The deprotection of such silyl ethers is carried out by fluoride-containing compounds, preferably tetrabutylammonium fluoride, tetraethylammonium fluoride, hydrofluoric acid, potassium fluoride, more preferably tetrabutylammonium fluoride, potassium fluoride. The dosage of the fluorine-containing reagent is 5 to 20 times the molar equivalent of the protected hydroxyl group, preferably 8 to 15 times the initiator. If the dosage of fluorine is less than 5 times the molar equivalent of the protected hydroxyl group, incomplete deprotection will occur; when the dosage of the deprotection reagent is greater than 20 times the molar equivalent of the protected hydroxyl group, the excessive reagent or compound will cause trouble in purification and may be mixed into subsequent steps, thus causing side reactions. There is no particular limitation on the reaction solvent, as long as it can dissolve the reactants and products, preferably aprotic solvents, more preferably tetrahydrofuran, dichloromethane. The reaction temperature is preferably 0 to 30 °C. When the temperature is lower than 0 °C, the reaction rate is slow and the protecting group cannot be completely removed. C: Deprotection of tert-butyl protecting group The deprotection of tert-butyl is carried out under acidic conditions, and the solution pH is preferably 0 to 4. The acid is not particularly limited, but preferably acetic acid, phosphoric acid, sulfuric acid, hydrochloric acid, nitric acid, more preferably hydrochloric acid. There is no particular limitation on the reaction solvent, as long as it can dissolve the reactants and products, preferably water. The reaction temperature is preferably 0 to 30 °C. 2.2.3. Alkylation reaction The alkylation reaction of the present invention is preferably a reaction based on the alkylation of hydroxyl, mercapto or amino groups, corresponding to the formation of ether bonds, thioether bonds, secondary amino or tertiary amino groups in turn. Examples are as follows: 2.2.3.1. Alkylation of substrate alcohol with sulfonate, halide In the presence of a base, an ether intermediate is obtained by nucleophilic substitution of a substrate alcohol with a sulfonate derivative, halide. Among them, the molar equivalent of the sulfonate, halide is 1 to 50 times that of the substrate alcohol, preferably 1 to 5 times. When the molar equivalent of the sulfonate, halide is less than 1 times the molar equivalent of the substrate alcohol, the reaction substitution is incomplete and difficult to purify. When the molar equivalent of the sulfonate, halide is greater than 50 times that of the substrate alcohol, the excessive reagent causes trouble in purification and may be mixed into subsequent steps, thus resulting in an increase in side reactions in the next step and an increase in the purification difficulty. The obtained product is a mixture of an ether intermediate and excessive sulfonate, halide, which can be purified by anion exchange resin, osmosis, ultrafiltration, etc. Among them, the anion exchange resin is not particularly limited, as long as the target product can undergo ion exchange and adsorption on the resin, preferably an ion exchange resin of tertiary amine or quaternary ammonium salt with dextran, agarose, polyacrylate, polystyrene, polydiphenylstyrene, etc. as the backbone. The solvents for osmosis and ultrafiltration are not limited, generally water or organic solvents. Among them, the organic solvents are not particularly limited, as long as the product can be dissolved in them, preferably dichloromethane, chloroform, etc. The reaction solvent is not limited, and aprotic solvents are preferred, such as toluene, benzene, xylene, acetonitrile, ethyl acetate, tetrahydrofuran, chloroform, dichloromethane, dimethyl sulfoxide, dimethylformamide or dimethylacetamide, and dimethylformamide, dichloromethane, dimethyl sulfoxide or tetrahydrofuran are more preferred. The base includes organic bases (such as triethylamine, pyridine, 4-dimethylaminopyridine, imidazole or diisopropylethylamine) or inorganic bases (such as sodium carbonate, sodium hydroxide, sodium bicarbonate, sodium acetate, potassium carbonate or potassium hydroxide), organic bases are preferred, and triethylamine and pyridine are more preferred. The molar amount of the base is 1 to 50 times the molar equivalent of the sulfonate or halide, preferably 1 to 10 times. 2.2.3.2. Alkylation of the substrate amine with sulfonate and halide In the presence of a base, an amine intermediate is obtained by nucleophilic substitution of the substrate amine with a sulfonate derivative or a halide. Among them, the molar equivalent of the sulfonate or halide is 1 to 50 times that of the substrate amine, preferably 1 to 5 times. When the molar equivalent of the sulfonate or halide is less than 1 times the molar equivalent of the substrate amine, the reaction substitution is incomplete and difficult to purify. When the molar equivalent of the sulfonate or halide is greater than 50 times that of the substrate amine, the excess reagent causes trouble in purification and may be mixed into subsequent steps, resulting in an increase in side reactions in the next step and an increase in purification difficulty. The obtained product is a mixture of an amine intermediate and excess sulfonate and halide, which can be purified by column chromatography, anion exchange resin, osmosis, ultrafiltration, etc. Among them, the anion exchange resin is not particularly limited as long as the target product can undergo ion exchange and adsorption on the resin, and ion exchange resins of tertiary amines or quaternary ammonium salts with skeletons such as dextran, agarose, polyacrylate, polystyrene, polydiphenylethylene, etc. are preferred. The solvents for osmosis and ultrafiltration are not limited, generally water or organic solvents, and the organic solvents are not particularly limited as long as the product can be dissolved in them, and dichloromethane, chloroform, etc. are preferred. The reaction solvent is not limited, and aprotic solvents are preferred, such as toluene, benzene, xylene, acetonitrile, ethyl acetate, tetrahydrofuran, chloroform, dichloromethane, dimethyl sulfoxide, dimethylformamide or dimethylacetamide, and dimethylformamide, dichloromethane, dimethyl sulfoxide or tetrahydrofuran are more preferred. The base includes organic bases (such as triethylamine, pyridine, 4-dimethylaminopyridine, imidazole or diisopropylethylamine) or inorganic bases (such as sodium carbonate, sodium hydroxide, sodium bicarbonate, sodium acetate, potassium carbonate or potassium hydroxide), organic bases are preferred, and triethylamine and pyridine are more preferred. The molar amount of the base is 1 to 50 times the molar equivalent of the sulfonate or halide, preferably 1 to 10 times, and more preferably 3 to 5 times. 2.2.3.3. Alkylation reaction of the substrate amine with aldehyde derivatives After obtaining an imine intermediate from the reaction of a substrate amine with an aldehyde derivative, an amine intermediate is obtained under the action of a reducing agent. Among them, the molar equivalent of the aldehyde derivative is 1 to 20 times that of the substrate amine, preferably 1 to 2 times, more preferably 1 to 1.5 times. When the molar equivalent of the aldehyde derivative is greater than 20 times that of the substrate amine, the excess reagent causes trouble in purification, may be mixed into subsequent steps, and increases the purification difficulty. When the molar equivalent of the aldehyde derivative is less than 1 time that of the substrate amine, the reaction is incomplete and the purification difficulty increases. Among them, the reaction product can be purified by means such as cation exchange resin, osmosis, ultrafiltration, etc. The cation exchange resin is not particularly limited as long as it can exchange with quaternary ammonium cations to achieve a separation effect. The solvents for osmosis and ultrafiltration are not limited. Generally, water or organic solvents can be used. The organic solvents are not particularly limited as long as the product can be dissolved in them. Dichloromethane, chloroform, etc. are preferred. The reaction solvent is not restricted, and organic solvents are preferred, such as methanol, ethanol, water, toluene, benzene, xylene, acetonitrile, ethyl acetate, tetrahydrofuran, chloroform, dichloromethane, dimethyl sulfoxide, dimethylformamide or dimethylacetamide, etc.; more preferably water and methanol. The reducing agent is not particularly restricted as long as it can reduce the imine to an amine. Sodium borohydride, lithium aluminum hydride, sodium cyanoborohydride, Zn / AcOH, etc. are preferred, and sodium cyanoborohydride is more preferred. Generally, the dosage of the reducing agent is 0.5 to 50 times the amount of substance of the aldehyde derivative, and more preferably 1 - 10 times. 3.1. Lipid Composition In the present invention, a lipid composition contains any one of the cationic lipids having the structure as shown in the general formula (1) described above. In a specific embodiment of the present invention, preferably, the lipid composition contains, in addition to the cationic lipid having the structure as shown in the general formula (1), one or more of phospholipids, steroid lipids, and polyethylene glycolated lipids, selected from any one of the following situations: Situation (1): Also contains phospholipids; Situation (2): Also contains steroid lipids; Situation (3): Also contains polyethylene glycolated lipids; Situation (4): Also contains phospholipids and steroid lipids; Situation (5): Also contains phospholipids and polyethylene glycolated lipids; Situation (6): Also contains steroid lipids and polyethylene glycolated lipids; Situation (7): Also contains phospholipids, steroid lipids, and polyethylene glycolated lipids; Situation (8): Also contains phospholipids, steroid lipids, polyethylene glycolated lipids, and another cationic lipid; Situation (9): Also contains phospholipids, steroid lipids, polyethylene glycolated lipids, and anionic lipids; More preferably, it also contains three kinds of lipids, namely neutral lipid, steroid lipid and polyethylene glycolated lipid, at the same time. In a specific embodiment of the present invention, the phospholipid in the lipid composition is preferably 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC), 1,2-dimyristoyl-sn-glycero-phosphocholine (DMPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-doundecanoyl-sn-glycero-phosphocholine (DUPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1,2-di-O-octadecenyl-sn-glycero-3-phosphocholine (18:0 Diether PC), 1-oleoyl-2-cholesteryl succinyl-sn-glycero-3-phosphocholine (OChemsPC), 1-hexadecyl-sn-glycero-3-phosphocholine (C16 Lyso PC), 1,2-dilinolenoyl-sn-glycero-3-phosphocholine, 1,2-diarachidonoyl-sn-glycero-3-phosphocholine, 1,2-didocosahexaenoyl-sn-glycero-3-phosphocholine, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), 1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine (ME 16.0PE), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, 1,2-dilinoleoyl-sn-glycero-3-phosphoethanolamine, 1,2-dilinolenoyl-sn-glycero-3-phosphoethanolamine, 1,2-diarachidonoyl-sn-glycero-3-phosphoethanolamine, 1,2-didocosahexaenoyl-sn-glycero-3-phosphoethanolamine, 1,2-dioleoyl-sn-glycero-3-phospho-rac-(1-glycerol) sodium salt (DOPG), dioleoyl phosphatidylserine (DOPS), dipalmitoyl phosphatidylglycerol (DPPG), palmitoyl oleoyl phosphatidylethanolamine (POPE), distearoyl-phosphatidylethanolamine (DSPE), dipalmitoyl phosphatidylethanolamine (DPPE), dimyristoyl phosphoethanolamine (DMPE), 1-stearoyl-2-oleoyl-stearoyl ethanolamine (SOPE), 1-stearoyl-2-oleoyl-phosphatidylcholine (SOPC), sphingomyelin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidic acid, palmitoyl oleoyl phosphatidylcholine, lysophosphatidylcholine and lysophosphatidylethanolamine (LPE), any one of them and their compositions. In a specific embodiment of the present invention, the sterol lipid in the lipid composition is preferably any one of cholesterol, coprosterol, sitosterol, ergosterol, campesterol, stigmasterol, brassicasterol, tomatidine, ursolic acid, α-tocopherol and their combinations. In a specific embodiment of the present invention, the polyethylene glycolylated lipid in the lipid composition is preferably any one of polyethylene glycol-1,2-dimyristoyl glycerol (PEG-DMG), polyethylene glycol-distearoyl phosphatidylethanolamine (PEG-DSPE), PEG-cholesterol, polyethylene glycol-diacylglycerol (PEG-DAG), polyethylene glycol-dialkoxypropyl (PEG-DAA), specifically including polyethylene glycol 500-dipalmitoyl phosphatidylcholine, polyethylene glycol 2000-dipalmitoyl phosphatidylcholine, polyethylene glycol 500-stearoyl phosphatidylethanolamine, polyethylene glycol 2000-distearoyl phosphatidylethanolamine, polyethylene glycol 500-1,2-dioleoyl phosphatidylethanolamine, polyethylene glycol 2000-1,2-dioleoyl phosphatidylethanolamine and polyethylene glycol 2000-2,3-dimyristoyl glycerol (PEG-DMG) and their combinations. In a specific embodiment of the present invention, the polyethylene glycolylated lipid in the lipid composition is preferably any one of the following structures and their combinations: Wherein, n1 is an integer from 20 to 300. In a specific embodiment of the present invention, another cationic lipid in the lipid composition is selected from any one of 1,2-dioleoyl-3-trimethylammonium-propane (methyl sulfate) (DOTAP), 1,2-bis(octadecenoxy)-3-methylammonium propane chloride (DOTMA), 1-[2-(oleoyloxy)ethyl]-2-oleyl-3-(2-hydroxyethyl)imidazoline chloride (DOTIM), 1,2-dioleoyl-3-dimethylamino-propane (DODMA), 2,3-bis(tetradecanoyloxy)propyltrimethylammonium chloride (DMTAP), didodecyldimethylammonium chloride (DDAC), didodecyldimethylammonium bromide (DDAB), N,N-dioleyl-N,N-dimethylammonium chloride (DODAC), N-(4-carboxybenzyl)-N,N-dimethyl-2,3-bis(oleoyloxy)propyl-1-ammonium (DOBAQ), 3,6-bis{4-[bis(2-hydroxydodecyl)amino]butyl}piperazine-2,5-dione (cKK-E12), 1,1'-((2-(4-(2-((2-(bis(2-hydroxydodecyl)amino)ethyl)(2-hydroxydodecyl)amino)ethyl)piperazin-1-yl)ethyl)azanediyl)bis(dodecan-2-ol) (C12-200), 4-(N,N-dimethylamino)butyric acid (dilinoleoyl)methyl ester (DLin-MC3-DMA), 1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine (EPC), ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate) (ALC-0315), 8-[(2-hydroxyethyl)(6-oxo-6-(undecyloxy)hexyl)amino]octanoic acid (heptadec-9-yl) ester (SM-102), and ((2-(2-hydroxyethoxy)ethyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate) (DHA-1). In a specific embodiment of the present invention, the anionic lipid in the lipid composition is selected from any one of 1,2-dioleoyl-sn-glycero-3-phosphate sodium salt (18:1PA), 1,2-dimyristoyl-sn-glycero-3-phosphate sodium salt (14:0PA), bis(monooleoylglycerol) phosphate ammonium salt (18:1BMP), and cardiolipin (CL). In a specific embodiment of the present invention, it contains 20-80% of the cationic lipid represented by formula (1), 5-16% of phospholipid, 25-55% of steroid lipid, and 0.5-10% of polyethylene glycolated lipid, and the percentages are the molar percentages of each lipid in the total lipid in the solution containing the solvent. In a specific embodiment of the present invention, preferably, any of the foregoing lipid compositions contains 20-80% of the cationic lipid represented by formula (1), 5-16% of phospholipid, 25-55% of steroid lipid, and 0.5-10% of polyethylene glycolated lipid, and the percentages are the molar percentages of each lipid in the total lipid in the solution containing the solvent. In a specific embodiment of the present invention, preferably, in any of the foregoing lipid compositions, the molar percentage of the cationic lipid in the total lipid in the solution containing the solvent is 30-65%; more preferably, it is any one of about 35%, 40%, 45%, 46%, 47%, 48%, 49%, 50%, 55%. In a specific embodiment of the present invention, preferably, in any of the foregoing lipid compositions, the molar percentage of the phospholipid in the total lipid in the solution containing the solvent is about 7.5-16%; more preferably, it is any one of about 8%, 9%, 10%, 11%, 12%, 16%. In a specific embodiment of the present invention, preferably, in any of the foregoing lipid compositions, the molar percentage of the steroid lipid in the total lipid in the solution containing the solvent is 35-50%, and more preferably, it is any one of about 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%. In a specific embodiment of the present invention, preferably, in any of the foregoing lipid compositions, the molar percentage of the polyethylene glycolated lipid in the total lipid in the solution containing the solvent is 0.5-5%; preferably, it is 1-3%; more preferably, it is any one of about 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2.0%, 2.5%. 3.2. Preparation of lipid composition In the present invention, the lipid composition can be prepared by the following methods, including but not limited to ethanol injection method, microfluidic method, T-tube mixing method, and membrane extrusion method. Preferably, the ethanol injection method and the microfluidic method are used. 4. Lipid drug composition and its preparation 4.1. Lipid drug composition In an embodiment of the present invention, a lipid drug composition contains any of the foregoing lipid compositions and a drug. Among them, the lipid composition contains any of the foregoing cationic lipids having a structure as shown in general formula (1), and the drug is selected from any one of nucleic acid drugs, gene vaccines, anti-tumor drugs, small molecule drugs, polypeptide drugs, or protein drugs. In a specific embodiment of the present invention, in the lipid drug composition, the nucleic acid drug is selected from any one of RNA, DNA, antisense nucleic acid, plasmid, interfering nucleic acid, aptamer, antagomir and ribozyme, and the RNA is selected from any one of mRNA, saRNA, circRNA, miRNA and siRNA; preferably, the nucleic acid drug is any one of DNA, mRNA, miRNA and siRNA. In a specific embodiment of the present invention, the lipid drug composition is preferably used as a drug and is selected from any one of the following drugs: antitumor agent, antiviral agent, antifungal agent and vaccine. In a specific embodiment of the present invention, the drugs in the lipid drug composition include but are not limited to doxorubicin, mitoxantrone, camptothecin, cisplatin, bleomycin, cyclophosphamide, streptozotocin, actinomycin D, vincristine, vinblastine, cytosine arabinoside, anthracycline, nitrogen mustard, thiotepa, chlorambucil, razoxane, melphalan, carmustine, lomustine, busulfan, dibromomannitol, mitomycin C, cis-dichlorodiammineplatinum(II), methotrexate, 6-mercaptopurine, 6-thioguanine, cytarabine, 5-fluorouracil, dacarbazine, dibucaine, chlorpromazine, propranolol, timolol, labetalol, clonidine, hydralazine, imipramine, amitriptyline, doxepin, phenytoin, diphenhydramine, chlorpheniramine, promethazine, gentamicin, ciprofloxacin, cefoxitin, miconazole, terconazole, econazole, isoconazole, butoconazole, clotrimazole, itraconazole, nystatin, naftifine, amphotericin B, antiparasitic agent, hormone, hormone antagonist, immunomodulator, neurotransmitter antagonist, antiglaucoma drug, vitamin, sedative, imaging agent, taxol, cytochalasin B, gramicidin D, ethidium bromide, emetine, mitomycin, etoposide, teniposide, colchicine, daunorubicin, mitoxantrone, mithramycin, 1-dehydrotestosterone, glucocorticoid, procaine, tetracaine, lidocaine, puromycin, maytansine. In a specific embodiment of the present invention, the N / P ratio of the lipid composition to the nucleic acid is preferably (0.1-100):1, more preferably (0.2-30):1, and most preferably (0.5-20):1. 4.1. Lipid Drug Composition Preparation In a specific embodiment of the present invention, the drug in the lipid drug composition is a nucleic acid drug, and the working solution of the lipid drug composition preparation is deionized water, ultrapure water, phosphate buffer or physiological saline, more preferably phosphate buffer or physiological saline, and most preferably physiological saline; preferably, lipid composition:working solution = (0.05-20) g:100 mL, more preferably (0.1-10) g:100 mL, and most preferably (0.2-5) g:100 mL. In a specific embodiment of the present invention, a lipid drug composition preparation contains the aforementioned lipid drug composition and a pharmaceutically acceptable diluent or excipient. The diluent or excipient is preferably any one of deionized water, ultrapure water, phosphate buffer solution, and physiological saline, more preferably phosphate buffer solution or physiological saline, and most preferably physiological saline. In the present invention, the preparation of the lipid drug composition preparation includes the following steps: (1) Equilibrate the lipid composition in the diluent or excipient; (2) Add the nucleic acid drug to the mixture of the equilibrated lipid composition and the diluent or excipient for complexation; Among them, preferably, the equilibration time is 0.1 - 12 h, preferably 0.2 - 6 h, and more preferably 0.5 - 3 h; preferably, the complexation time is 0.1 - 12 h, preferably 0.2 - 5 h, and more preferably 0.5 - 2 h. 5. Liposomes or lipid nanoparticles and their preparation 5.1. Liposomes or lipid nanoparticles In a specific embodiment of the present invention, a liposome or lipid nanoparticle contains any one of the aforementioned lipid drug compositions. In a specific embodiment of the present invention, preferably, the aforementioned lipid nanoparticle is an LNP - drug composition, an LPP - drug composition, or a PNP - drug composition; preferably an LNP - drug composition; more preferably an LNP - nucleic acid drug composition; and more preferably an LNP - mRNA drug composition. 5.2. Preparation of liposomes or lipid nanoparticles In a specific embodiment of the present invention, liposomes can be prepared by the following methods, including but not limited to thin - film dispersion method, ultrasonic dispersion method, reverse - phase evaporation method, freeze - drying method, freeze - thaw method, multiple - emulsion method, and injection method, preferably the thin - film dispersion method, ultrasonic dispersion method, and / or reverse - phase evaporation method. In a specific embodiment of the present invention, lipid nanoparticles can be prepared by the following methods, including but not limited to microemulsion method, multiple - emulsion method, high - shear homogenization ultrasonic method, thin - film hydration extrusion method, and microfluidic method. In a specific embodiment of the present invention, liposomes are prepared by the thin - film dispersion method, and the thin - film dispersion method includes the following steps: (1) Weigh cationic lipid, steroid lipid, neutral lipid, and polyethylene glycol - modified lipid, dissolve them fully in an organic solvent, shake well, remove the organic solvent by rotary evaporation under reduced pressure to form an oil film, and dry it with a vacuum pump to remove the organic solvent; (2) Add phosphate buffer solution containing a cryoprotectant, and perform water - bath ultrasonic treatment to form a semi - transparent emulsion; (3) Add the emulsion to a high-pressure homogenizer for overpressure, and then add the overpressurized emulsion to a liposome extruder for membrane filtration to form liposomes; (4) Optionally, dry the liposomes in a freeze dryer to form liposome powder. In a specific embodiment of the present invention, in the method for preparing liposomes, the ratio of liposomes to phosphate buffer solution dissolved with cryoprotectant can be 1 mg:(0.1 - 100) mL, preferably 1 mg:(0.3 - 50) mL, more preferably 1 mg:(0.5 - 5) mL. In a specific embodiment of the present invention, preferably, lipid nanoparticles are prepared by microfluidics, vortex or simple mixing methods, and the steps are as follows: (1) Dissolve each lipid component in an organic solvent to obtain a lipid composition dissolved in the organic phase; the organic phase is preferably ethanol; (2) Add the nucleic acid drug to a buffer solution to obtain an aqueous solution; the aqueous phase is preferably citrate buffer salt or sodium acetate buffer solution; (3) Mix the organic phase solution and the aqueous solution through a microfluidic device, vortex or pipette to form a lipid nanoparticle composition, and purify it by ultrafiltration, etc. to remove organic solvents and free nucleic acid molecules. The preparation method of the present invention includes any protection and deprotection processes for specific groups required by the reaction. The intermediates and end products prepared in the present invention can be purified by methods including but not limited to extraction, recrystallization, adsorption treatment, precipitation, antprecipitation, thin film dialysis, supercritical extraction, column chromatography (including gel column, ion column, silica gel column, etc.). The characterization of the structure, molecular weight and purity of the intermediates and end products can be carried out by methods including but not limited to 1 H NMR, electrophoresis, ultraviolet-visible spectrophotometer, FTIR, AFM, GPC, HPLC, MALDI-TOF MS and circular dichroism spectrometry, etc. In the present invention, the structure of the cationic lipid end product is characterized by nuclear magnetic resonance, and the molecular weight is confirmed by mass spectrometry; the molecular weight (by default, the number average molecular weight Mn) and polydispersity index (PDI) of the polymer are determined by gel permeation chromatography (GPC), and the degree of polymerization of the polymer (by default, the number average degree of polymerization) is calculated according to its molecular weight. The following describes in further detail the preparation methods of cationic lipids, lipid compositions, lipid drug compositions, lipid drug composition preparations and the biological activity tests of lipid drug compositions with some specific examples. The specific examples are to further illustrate the present invention in detail and do not limit the protection scope of the present invention. Example 1: Cationic lipid E1-1 The preparation process is as follows: Step a: Dissolve piperazine-1,4-diacetic acid (S1-1, 0.61 g, 3.0 mmol) in acetonitrile (30 mL), add N,N'-diisopropylcarbodiimide (DIC, 1.51 g, 12.0 mmol), and then sequentially add 4-dimethylaminopyridine (DMAP, 0.55 g, 4.5 mmol) and 4-bromo-1-butanol (S1-2, 1.84 g, 12.0 mmol) to the solution. Stir the reaction mixture at room temperature overnight. After the reaction is completed, filter, concentrate the filtrate, dissolve the residue in dichloromethane (30 mL), and wash the resulting solution with water (10 mL * 2) and brine (30 mL * 1) in sequence. Combine the organic phases, dry over anhydrous magnesium sulfate, filter, concentrate, and purify the crude product by column chromatography to obtain S1-3 (1.34 g, 94.3%). Step b: Sequentially add Boc-N(Me)Glu-OH (S1-4, 2.09 g, 8.0 mmol), p-toluenesulfonic acid (TsOH, 1.51 g, 8.8 mmol), and anhydrous toluene (20 mL) to a 250 mL reaction flask, then heat the reaction solution to 135 °C and reflux for 3 h. After the reaction is completed, cool the reaction solution to room temperature, add linolenyl alcohol (S1-5, 4.47 g, 16.8 mmol) in batches, and heat to 135 °C and reflux overnight. After the reaction is completed, concentrate the reaction solution, dissolve the residue in dichloromethane, wash with water twice, saturated sodium bicarbonate aqueous solution twice, and saturated brine once in sequence, and finally dry over anhydrous magnesium sulfate, filter, concentrate the filtrate, and purify the crude product by column chromatography to obtain the esterified product with secondary amino Boc protection (3.75 g). Remove the Boc protecting group. In a dry and clean round-bottom flask, prepare a solution of trifluoroacetic acid / dichloromethane (1:2, v / v), and slowly add a dichloromethane solution of the above esterified product (3.03 g, 4.0 mmol) dropwise under ice bath conditions and react at room temperature for 2 h. After the reaction is completed, add water to the reaction solution, stir evenly, extract, dry the organic phase over anhydrous magnesium sulfate, filter, concentrate the filtrate, and recrystallize to obtain S1-6 (2.44 g). Step c: Under nitrogen protection, dissolve the above compound S1-6 (1.45 g, 2.2 mmol) in acetonitrile (20 mL), sequentially add S1-3 (0.47 g, 1.0 mmol) and N,N-diisopropylethylamine (DIPEA, 0.28 g, 2.2 mmol) under slow stirring, and stir at room temperature for about 20 h. After the reaction is completed, concentrate the reaction solution, then dissolve it in dichloromethane, extract with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution in sequence, combine the organic phases, dry over anhydrous magnesium sulfate, filter, concentrate the filtrate, and purify the crude product by column chromatography to obtain the cationic lipid E1-1 (1.17 g). 11H NMR (400 MHz, CDCl3) δ: 5.45 - 5.26 (m, 16H, -CH=CH-), 4.17 - 4.00 (m, 12H, -C(=O)OCH2-), 3.28 - 3.22 (m, 2H, >NCH<), 3.20 (s, 4H, pip-CH2-), 2.77 (t, 8H, -CH=CHCH2CH=CH-), 2.65 (s, 8H, pip-H), 2.60 - 2.43 (m, 4H, >NCH2-), 2.41 - 2.34 (m, 4H, >CHCH2CH2-), 2.26 (s, 6H, >NCH3), 2.09 - 1.91 (m, 20H; 4H, >CHCH2-; 16H, -CH=CHCH2-), 1.64 - 1.25 (m, 80H, -CH2CH2CH2-, -CH2CH3), 0.89 (t, 12H, -CH2CH3). MS (ESI): m / z = 1626.3 ([M+H] + )。 Example 2: Cationic Lipid E2-1 The preparation process is as follows: Step a: Under nitrogen protection, add N,N'-dicyclohexylcarbodiimide (DCC, 6.34 g, 30.8 mmol) to a round-bottom flask containing undecanol (S2-2, 2.89 g, 16.8 mmol), 6-hydroxyhexanoic acid with Boc-protected hydroxyl group (S2-1, 3.44 g, 14.0 mmol), and DMAP (0.43 g, 3.5 mmol) dissolved in dichloromethane (100 mL), and react at room temperature for 16 h. After the reaction is completed, remove the precipitate by filtration, concentrate the filtrate, and purify the crude product by column chromatography to obtain S2-3 (4.67 g). Step b: Dissolve the above compound S2-3 (4.41 g, 11.0 mmol) in THF (30 mL) solution, place it in a flask under nitrogen protection, add TBAF solution (30 mL, 1 M), and react overnight to remove the TBS protection. After the reaction is completed, concentrate, extract, combine the organic phases, dry over anhydrous magnesium sulfate, filter and concentrate, and purify by column chromatography to obtain S2-4 (2.81 g, 88.4%). Step c: Add S1-4 (1.04 g, 4.0 mmol), TsOH (0.76 g, 4.4 mmol) and anhydrous toluene (20 mL) into a 250 mL reaction flask in sequence. Subsequently, heat the reaction solution to 135 °C and reflux for 3 h. After the reaction is completed, cool the reaction solution to room temperature, add S2-4 (2.40 g, 8.4 mmol) in batches, and heat to 135 °C for reflux overnight. After the reaction is completed, concentrate the reaction solution, dissolve the residue in dichloromethane, wash twice with water, twice with saturated sodium bicarbonate aqueous solution, once with saturated brine, and finally dry with anhydrous magnesium sulfate, filter, concentrate the filtrate, and purify the crude product by column chromatography to obtain the esterified product with secondary amino Boc protection (2.01 g). Remove the Boc protecting group. In a dry and clean round-bottomed flask, prepare a solution of trifluoroacetic acid / dichloromethane (1:2, v / v), and slowly add the dichloromethane solution of the above esterified product (1.76 g, 2.2 mmol) dropwise under ice bath conditions, and react at room temperature for 2 h. After the reaction is completed, add water to the reaction solution, stir evenly, extract, dry the organic phase with anhydrous magnesium sulfate, filter, concentrate the filtrate, and recrystallize to obtain S2-5 (1.43 g). Step d: Under nitrogen protection, dissolve the above compound S2-5 (1.23 g, 1.8 mmol) in acetonitrile (20 mL), and sequentially add S1-3 (0.38 g, 0.8 mmol) and DIPEA (0.23 g, 1.8 mmol) under slow stirring, and stir at room temperature for about 20 h. After the reaction is completed, concentrate the reaction solution, then dissolve it in dichloromethane, extract with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution in sequence, combine the organic phases, dry with anhydrous magnesium sulfate, filter, concentrate the filtrate, and purify the crude product by column chromatography to obtain the cationic lipid E2-1 (1.00 g). 1 H NMR (400 MHz, CDCl3) δ: 1 H NMR (400 MHz, CDCl3) δ: 4.14 - 4.02 (m, 20H, -C(=O)OCH2-), 3.27 - 3.22 (m, 2H, >NCH<), 3.20 (s, 4H, pip-CH2-), 2.65 (s, 8H, pip-H), 2.59 - 2.54 (m, 2H, >NCH2-), 2.48 - 2.42 (m, 2H, >NCH2-), 2.40 - 2.34 (m, 4H, >CHCH2CH2-), 2.31 (t, 8H, -CH2C(=O)O-), 2.25 (s, 6H, >NCH3), 2.00 - 1.91 (m, 4H, >CHCH2-), 1.68 - 1.22 (m, 104H, -CH2CH2CH2-,-CH2CH3), 0.87 (t, 12H, -CH2CH3). MS (ESI): m / z=1706.3 ([M+H]+ )。 Example 3: Cationic Lipid E3-1 The preparation process is as follows: Step a: Under nitrogen protection, DCC (4.53 g, 22.0 mmol) was added to a round-bottom flask containing 4-(tert-butyldimethylsilyl)oxy-1-butanol (S3-1, 2.45 g, 12.0 mmol), 2-decenoic acid (S3-2, 1.70 g, 10.0 mmol), and DMAP (0.31 g, 2.5 mmol) dissolved in dichloromethane (80 mL), and the reaction was carried out at room temperature for 16 h. After the reaction was completed, the precipitate was removed by filtration, the filtrate was concentrated, and the crude product was purified by column chromatography to obtain S3-3 (2.93 g). Step b: The above compound S3-3 (2.85 g, 8.0 mmol) was dissolved in THF (20 mL) solution, placed in a flask under nitrogen protection, and TBAF solution (20 mL, 1 M) was added. The reaction was carried out overnight to remove the TBS protection. After the reaction was completed, the mixture was concentrated, extracted, and the organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and concentrated. The crude product was purified by column chromatography to obtain S3-4 (1.71 g, 88.4%). Step c: S1-4 (0.78 g, 3.0 mmol), TsOH (0.57 g, 3.3 mmol), and anhydrous toluene (20 mL) were successively added to a 250 mL reaction flask. Subsequently, the reaction solution was heated to 135 °C and refluxed for 3 h. After the reaction was completed, the reaction solution was cooled to room temperature, and S3-4 (1.44 g, 6.3 mmol) was added in batches, and the temperature was raised to 135 °C and refluxed overnight. After the reaction was completed, the reaction solution was concentrated, and the residue was dissolved in dichloromethane, washed twice with water, twice with saturated sodium bicarbonate aqueous solution, once with saturated brine, and finally dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. The crude product was purified by column chromatography to obtain the esterified product with secondary amino Boc protection (1.34 g). The Boc protecting group was removed. In a dry and clean round-bottom flask, a solution of trifluoroacetic acid / dichloromethane (1:2, v / v) was prepared, and the dichloromethane solution of the above esterified product (1.21 g, 1.7 mmol) was slowly added dropwise under ice bath conditions, and the reaction was carried out at room temperature for 2 hours. After the reaction was completed, water was added to the reaction solution and stirred evenly, extracted, the organic phase was dried over anhydrous magnesium sulfate, filtered, the filtrate was concentrated, and recrystallized to obtain S3-5 (0.96 g). Step d: Under nitrogen protection, dissolve the above compound S3-5 (0.81 g, 1.3 mmol) in acetonitrile (10 mL). While stirring slowly, add S1-3 (0.28 g, 0.6 mmol) and DIPEA (0.17 g, 1.3 mmol) successively, and stir the reaction at room temperature for about 20 h. After the reaction is completed, concentrate the reaction solution, then dissolve it with dichloromethane, extract it successively with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution, combine the organic phases, dry them with anhydrous magnesium sulfate, filter, concentrate the filtrate, and purify the crude product by column chromatography to obtain the cationic lipid E3-1 (0.67 g). 1 H NMR(400MHz,CDCl3)δ:7.06-6.99(m,4H,-CH=CHCH2-),5.84-5.78(m,4H,-CH=CHCH2-),4.14-4.04(t,20H,-C(=O)OCH2-),3.26-3.22(m,2H,>NCH<),3.21(s,4H,pip-CH2-),2.64(s,8H,pip-H),2.61-2.43(m,4H,>NCH2-),2.40-2.25(m,10H;4H,>CHCH2CH2-;6H,>NCH3),2.10-1.91(m,12H;4H,>CHCH2-;8H,-CH=CHCH2-),1.62-1.22(m,64H,-CH2CH2CH2-,-CH2CH3),0.87(t,12H,-CH2CH3). MS(ESI):m / z=1530.0([M+H] + )。 Example 4: Cationic lipid E4-1 The preparation process is as follows: Step a: Under nitrogen protection, add DCC (4.53 g, 22.0 mmol) to a round-bottom flask containing 4-nonyne-1-ol (S4-2, 2.74 g, 10.0 mmol), hydroxy Boc-protected 8-hydroxyoctanoic acid (S4-1, 1.68 g, 12.0 mmol) and DMAP (0.31 g, 2.5 mmol) dissolved in dichloromethane (50 mL), and react at room temperature for 16 h. After the reaction is completed, remove the precipitate by filtration, concentrate the filtrate, and purify the crude product by column chromatography to obtain S4-3 (3.26 g). Step b: Dissolve the above compound S4-3 (3.18 g, 8.0 mmol) in THF (20 mL) solution, place it in a flask under nitrogen protection, add TBAF solution (20 mL, 1 M), react overnight to remove the TBS protection. After the reaction, concentrate, extract, and combine the organic phases, dry over anhydrous magnesium sulfate, filter and concentrate, and purify by column chromatography to obtain S4-4 (1.98 g, 87.9%). Step c: Add S1-4 (0.78 g, 3.0 mmol), TsOH (0.57 g, 3.3 mmol) and anhydrous toluene (20 mL) to a 250 mL reaction flask in sequence, then heat the reaction solution to 135 °C and reflux for 3 h. After the reaction is completed, cool the reaction solution to room temperature, add S4-4 (1.78 g, 6.3 mmol) in batches, and heat to 135 °C and reflux overnight. After the reaction, concentrate the reaction solution, dissolve the residue in dichloromethane, wash twice with water, twice with saturated sodium bicarbonate aqueous solution, once with saturated brine, and finally dry over anhydrous magnesium sulfate, filter, concentrate the filtrate, and purify the crude product by column chromatography to obtain the esterified product with secondary amino Boc protection (1.49 g). Remove the Boc protecting group. In a dry and clean round-bottomed flask, prepare a solution of trifluoroacetic acid / dichloromethane (1:2, v / v), and slowly add the dichloromethane solution of the above esterified product (1.42 g, 1.8 mmol) dropwise under ice bath conditions, and react at room temperature for 2 h. After the reaction, add water to the reaction solution and stir evenly, extract, dry the organic phase over anhydrous magnesium sulfate, filter, concentrate the filtrate, and recrystallize to obtain S4-5 (1.15 g). Step d: Under nitrogen protection, dissolve the above compound S4-5 (0.91 g, 1.3 mmol) in acetonitrile (10 mL), and sequentially add S1-3 (0.28 g, 0.6 mmol) and DIPEA (0.17 g, 1.3 mmol) under slow stirring, and stir at room temperature for about 20 h. After the reaction, concentrate the reaction solution, then dissolve it in dichloromethane, extract with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution in sequence, combine the organic phases, dry over anhydrous magnesium sulfate, filter, concentrate the filtrate, and purify the crude product by column chromatography to obtain the cationic lipid E4-1 (0.74 g). 11H NMR (400 MHz, CDCl3) δ: 4.14 - 4.04 (m, 20H, -C(=O)OCH2-), 3.27 - 3.22 (m, 2H, >NCH<), 3.20 (s, 4H, pip-CH2-), 2.66 (s, 8H, pip-H), 2.61 - 2.42 (m, 4H, >NCH2-), 2.27 - 2.20 (m, 26H; 8H, -C≡CCH2CH2CH2OC(=O)-; 4H, >CHCH2CH2-; 8H, -CH2C(=O)O-; 6H, >NCH3), 2.17 - 2.10 (m, 8H, -C≡CCH2CH2CH2CH3), 2.01 - 1.91 (m, 4H, >CHCH2-), 1.84 - 1.76 (m, 8H, -C(=O)OCH2CH2CH2C≡C-), 1.62 - 1.22 (m, 64H, -CH2CH2CH2-, -CH2CH3), 0.86 (t, 12H, -CH2CH3). MS (ESI): m / z = 1689.7 ([M+H] + )。 Example 5: Cationic Lipid E5-1 The preparation process is as follows: Step a: Add N-Boc protected methyl aspartic acid (S5-1, 0.74 g, 3.0 mmol), TsOH (0.57 g, 3.3 mmol) and anhydrous toluene (30 mL) to a 250 mL reaction flask in sequence. Then heat the reaction solution to 135 °C and reflux for 3 h. After the reaction is completed, cool the reaction solution to room temperature, add S1-5 (1.68 g, 6.3 mmol) in batches, and heat to 135 °C and reflux overnight. After the reaction is over, concentrate the reaction solution, dissolve the residue in dichloromethane, wash it twice with water, twice with saturated sodium bicarbonate aqueous solution, once with saturated brine, and finally dry it with anhydrous magnesium sulfate, filter, concentrate the filtrate, and purify the crude product by column chromatography to obtain the N-Boc protected ester (1.42 g). Remove the Boc protecting group. In a dry and clean round-bottom flask, prepare a solution of trifluoroacetic acid / dichloromethane (1:2, v / v), and slowly add the dichloromethane solution of the above ester (1.34 g, 1.8 mmol) dropwise under ice bath conditions, and react at room temperature for 2 h. After the reaction is completed, add water to the reaction solution and stir evenly, extract, dry the organic phase with anhydrous magnesium sulfate, filter, concentrate the filtrate, and recrystallize to obtain S5-2 (1.09 g). Step b: Under nitrogen protection, dissolve the above compound S5-2 (0.85 g, 1.3 mmol) in acetonitrile (10 mL). While stirring slowly, sequentially add S1-3 (0.28 g, 0.6 mmol) and DIPEA (0.17 g, 1.3 mmol), and stir the reaction at room temperature for about 20 h. After the reaction is completed, concentrate the reaction solution, then dissolve it in dichloromethane, and extract it successively with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution. Combine the organic phases, dry them with anhydrous magnesium sulfate, filter, concentrate the filtrate, and purify the crude product by column chromatography to obtain the cationic lipid E5-1 (0.71 g). 1 H NMR (400 MHz, CDCl3) δ: 5.45 - 5.26 (m, 16H, -CH=CH-), 4.14 - 4.04 (m, 12H, -C(=O)OCH2-), 3.83 - 3.78 (m, 2H, >NCH<), 3.21 (s, 4H, pip-CH2-), 2.85 - 2.70 (m, 10H; 2H, >CHCH2-; 8H, -CH=CHCH2CH=CH-), 2.64 (s, 8H, pip-H), 2.61 - 2.41 (m, 6H; 2H, >CHCH2-; 4H, >NCH2-), 2.36 (s, 6H, >NCH3), 2.03 - 1.97 (m, 16H, -CH=CHCH2-), 1.62 - 1.22 (m, 80H, -CH2CH2CH2-, -CH2CH3), 0.88 (t, 12H, -CH2CH3). MS (ESI): m / z=1597.30 ([M+H] + )。 Example 6: Cationic Lipid E6-1 The preparation process is as follows: Step a: Add S5-1 (0.74 g, 3.0 mmol), TsOH (0.57 g, 3.3 mmol) and anhydrous toluene (20 mL) into a 250 mL reaction flask in sequence. Subsequently, heat the reaction solution to 135 °C and reflux for 3 h. After the reaction is completed, cool the reaction solution to room temperature, add S2-4 (1.54 g, 6.3 mmol) in batches, and heat to 135 °C for reflux overnight. After the reaction is completed, concentrate the reaction solution. The residue is dissolved in dichloromethane, washed twice with water, twice with saturated sodium bicarbonate aqueous solution, once with saturated brine, and finally dried over anhydrous magnesium sulfate, filtered, and the filtrate is concentrated. The crude product is purified by column chromatography to obtain the esterified product with secondary amino Boc protection (1.51 g). Remove the Boc protecting group. In a dry and clean round-bottom flask, prepare a solution of trifluoroacetic acid / dichloromethane (1:2, v / v). Slowly add the dichloromethane solution of the above esterified product (1.15 g, 1.8 mmol) dropwise under ice bath conditions and react at room temperature for 2 h. After the reaction is completed, add water to the reaction solution, stir evenly, extract, dry the organic phase over anhydrous magnesium sulfate, filter, concentrate the filtrate, and recrystallize to obtain S6-1 (1.15 g). Step b: Under nitrogen protection, dissolve the above compound S6-1 (0.90 g, 1.3 mmol) in acetonitrile (10 mL). Slowly add S1-3 (0.28 g, 0.6 mmol) and DIPEA (0.17 g, 1.3 mmol) in sequence under slow stirring, and stir at room temperature for about 20 h. After the reaction is completed, concentrate the reaction solution, then dissolve it with dichloromethane, extract with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution in sequence, combine the organic phases, dry over anhydrous magnesium sulfate, filter, concentrate the filtrate, and purify the crude product by column chromatography to obtain the cationic lipid E6-1 (0.74 g). 1 H NMR (400 MHz, CDCl3) δ: 4.14 - 4.04 (t, 20H, -C(=O)OCH2-), 3.83 - 3.78 (m, 2H, >NCH<), 3.20 (s, 4H, pip-CH2-), 2.84 - 2.78 (m, 2H, >CHCH2-), 2.66 (s, 8H, pip-H), 2.60 - 2.42 (m, 6H; 2H, >CHCH2-; 4H, >NCH2-), 2.36 (s, 6H, >NCH3), 2.23 (t, 8H, -CH2C(=O)O-), 1.62 - 1.22 (m, 104H, -CH2CH2CH2-,-CH2CH3), 0.88 (t, 12H, -CH2CH3). MS (ESI): m / z=1677.3 ([M+H] + )。 Example 7: Cationic Lipid E7-1 The preparation process is as follows: Step a: Add S5-1 (0.74 g, 3.0 mmol), TsOH (0.57 g, 3.3 mmol) and anhydrous toluene (20 mL) into a 250 mL reaction flask in sequence. Subsequently, heat the reaction solution to 135 °C and reflux for 3 h. After the reaction is completed, cool the reaction solution to room temperature, add S3-4 (1.44 g, 6.3 mmol) in batches, and heat to 135 °C for reflux overnight. After the reaction is over, concentrate the reaction solution. The residue is dissolved in dichloromethane, washed twice with water, twice with saturated sodium bicarbonate aqueous solution, once with saturated brine, and finally dried with anhydrous magnesium sulfate, filtered, the filtrate is concentrated, and the crude product is purified by column chromatography to obtain the esterified product with secondary amino Boc protection (1.31 g). Remove the Boc protecting group. In a dry and clean round-bottomed flask, prepare a solution of trifluoroacetic acid / dichloromethane (1:2, v / v), and slowly dropwise add the dichloromethane solution of the above esterified product (1.25 g, 1.8 mmol) under ice bath conditions, and react at room temperature for 2 h. After the reaction is completed, add water to the reaction solution, stir evenly, extract, dry the organic phase with anhydrous magnesium sulfate, filter, concentrate the filtrate, and recrystallize to obtain S7-1 (1.01 g). Step b: Under nitrogen protection, dissolve the above compound S7-1 (0.79 g, 1.3 mmol) in acetonitrile (10 mL), and sequentially add S1-3 (0.28 g, 0.6 mmol) and DIPEA (0.17 g, 1.8 mmol) under slow stirring, and stir at room temperature for about 20 h. After the reaction is completed, concentrate the reaction solution, then dissolve it in dichloromethane, extract with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution in sequence, combine the organic phases, dry with anhydrous magnesium sulfate, filter, concentrate the filtrate, and purify the crude product by column chromatography to obtain the cationic lipid E7-1 (0.66 g). 11H NMR (400 MHz, CDCl3) δ: 7.06 - 6.99 (m, 4H, -CH=CHCH2-), 5.83 - 5.79 (m, 4H, -CH=CHCH2-), 4.14 - 4.04 (t, 20H, -C(=O)OCH2-), 3.83 - 3.78 (m, 2H, >NCH<), 3.22 (s, 4H, pip-CH2-), 2.84 - 2.78 (m, 2H, >CHCH2-), 2.65 (s, 8H, pip-H), 2.61 - 2.43 (m, 6H; 2H, >CHCH2-; 4H, >NCH2-), 2.36 (s, 6H, >NCH3), 2.09 - 1.90 (m, 8H, -CH=CHCH2-), 1.62 - 1.22 (m, 64H, -CH2CH2CH2-,-CH2CH3), 0.89 (t, 12H, -CH2CH3). MS (ESI): m / z=1501.0 ([M+H] + )。 Example 8: Cationic Lipid E8-1 The preparation process is as follows: Step a: Add S5-1 (0.74 g, 3.0 mmol), TsOH (0.57 g, 3.3 mmol) and anhydrous toluene (20 mL) into a 250 mL reaction flask in sequence. Then heat the reaction solution to 135 °C and reflux for 3 h. After the reaction is completed, cool the reaction solution to room temperature, add S4-4 (1.78 g, 6.3 mmol) in batches, and heat to 135 °C for reflux overnight. After the reaction is over, concentrate the reaction solution. The residue is dissolved in dichloromethane, washed twice with water, twice with saturated sodium bicarbonate aqueous solution, once with saturated brine, and finally dried with anhydrous magnesium sulfate, filtered, and the filtrate is concentrated. The crude product is purified by column chromatography to obtain the esterified product with secondary amino Boc protection (1.49 g). Remove the Boc protecting group. In a dry and clean round-bottom flask, prepare a solution of trifluoroacetic acid / dichloromethane (1:2, v / v). Slowly add the dichloromethane solution of the above esterified product (1.40 g, 1.8 mmol) dropwise under ice bath conditions and react at room temperature for 2 h. After the reaction is completed, add water to the reaction solution, stir evenly, extract, dry the organic phase with anhydrous magnesium sulfate, filter, concentrate the filtrate, and recrystallize to obtain S8-1 (1.14 g). Step b: Under nitrogen protection, dissolve the above compound S8-1 (0.89 g, 1.3 mmol) in acetonitrile (10 mL). While stirring slowly, sequentially add S1-3 (0.28 g, 0.6 mmol) and DIPEA (0.17 g, 1.3 mmol). Stir the reaction mixture at room temperature for about 20 h. After the reaction is completed, concentrate the reaction solution, then dissolve it in dichloromethane, and extract it successively with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution. Combine the organic phases, dry them over anhydrous magnesium sulfate, filter, concentrate the filtrate, and purify the crude product by column chromatography to obtain the cationic lipid E8-1 (0.74 g). 1 H NMR (400 MHz, CDCl3) δ: 4.14 - 4.04 (m, 20H, -C(=O)OCH2-), 3.83 - 3.78 (m, 2H, >NCH<), 3.22 (s, 4H, pip-CH2-), 2.84 - 2.78 (m, 2H, >CHCH2-), 2.65 (s, 8H, pip-H), 2.62 - 2.42 (m, 6H; 2H, >CHCH2-; 4H, >NCH2-), 2.36 (s, 6H, >NCH3), 2.27 - 2.23 (m, 16H; 8H, -C≡CCH2CH2CH2OC(=O)-; 8H, -CH2C(=O)O-), 2.17 - 2.10 (m, 8H, -C≡CCH2CH2CH2CH3), 1.84 - 1.76 (m, 8H, -C(=O)OCH2CH2CH2C≡C-), 1.62 - 1.22 (m, 64H, -CH2CH2CH2-, -CH2CH3), 0.88 (t, 12H, -CH2CH3). MS (ESI): m / z=1661.1 ([M+H] + )。 Example 9: Cationic lipid E9-1 The preparation process is as follows: Step a: Dissolve S1-1 (0.61 g, 3.0 mmol) in acetonitrile (30 mL), and add DIC (1.51 g, 12.0 mmol). Then, sequentially add DMAP (0.55 g, 4.5 mmol) and bromo-diglycol (S9-1, 2.56 g, 12.0 mmol) to the solution. Stir the reaction mixture at room temperature overnight. After the reaction is completed, filter, concentrate the filtrate, dissolve the residue in dichloromethane (30 mL), and wash the resulting solution successively with water (10 mL * 2) and brine (30 mL * 1). Combine the organic phases, dry them over anhydrous magnesium sulfate, filter, concentrate, and purify the crude product by column chromatography to obtain S9-2 (1.44 g, 95.1%). Step b: Under nitrogen protection, dissolve the above compound S9-2 (0.89 g, 1.8 mmol) in acetonitrile (20 mL). Sequentially add S1-6 (0.53 g, 0.8 mmol) and DIPEA (0.23 g, 1.8 mmol) under slow stirring, and stir the reaction at room temperature for about 20 h. After the reaction is completed, concentrate the reaction solution, then dissolve it with dichloromethane, extract it successively with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution, combine the organic phases, dry with anhydrous magnesium sulfate, filter, concentrate the filtrate, and purify the crude product by column chromatography to obtain the cationic lipid E9-1 (0.98 g). 1 H NMR (400 MHz, CDCl3) δ: 5.45 - 5.26 (m, 16H, -CH=CH-), 4.25 (t, 4H, -C(=O)OCH2CH2O-), 4.14 - 4.04 (t, 8H, -C(=O)OCH2-), 3.67 - 3.62 (m, 4H, -C(=O)OCH2CH2O-), 3.55 - 3.49 (m, 4H, -OCH2CH2N<-), 3.28 - 3.22 (m, 2H, >NCH<), 3.20 (s, 4H, pip-CH2-), 2.78 - 2.70 (m, 12H; 4H, >NCH2-; 8H, -CH=CHCH2CH=CH-), 2.66 (s, 8H, pip-H), 2.40 - 2.34 (m, 4H, >CHCH2CH2-), 2.26 (s, 6H, >NCH3), 2.09 - 1.89 (m, 20H; 4H, >CHCH2-; 16H, -CH=CHCH2-), 1.63 - 1.22 (m, 72H, -CH2CH2CH2-, -CH2CH3), 0.87 (t, 12H, -CH2CH3). MS (ESI): m / z=1657.3 ([M+H] + )。 Example 10: Cationic lipid E10-1 The preparation process is as follows: Under nitrogen protection, dissolve the compound S9-2 (0.89 g, 1.8 mmol) in acetonitrile (20 mL). Sequentially add S2-5 (0.56 g, 0.8 mmol) and DIPEA (0.23 g, 1.8 mmol) under slow stirring, and stir the reaction at room temperature for about 20 h. After the reaction is completed, concentrate the reaction solution, then dissolve it with dichloromethane, extract it successively with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution, combine the organic phases, dry with anhydrous magnesium sulfate, filter, concentrate the filtrate, and purify the crude product by column chromatography to obtain the cationic lipid E10-1 (1.01 g). 11H NMR (400 MHz, CDCl3) δ: 4.25 (t, 4H, -C(=O)OCH2CH2O-), 4.14 - 4.04 (m, 16H, -C(=O)OCH2-), 3.67 - 3.62 (m, 4H, -C(=O)OCH2CH2O-), 3.55 - 3.49 (m, 4H, -OCH2CH2N<-), 3.28 - 3.22 (m, 2H, >NCH<), 3.21 (s, 4H, pip-CH2-), 2.78 - 2.70 (m, 4H, >NCH2-), 2.67 (s, 8H, pip-H), 2.40 - 2.34 (m, 4H, >CHCH2CH2-), 2.32 (t, 8H, -CH2C(=O)O-), 2.25 (s, 6H, >NCH3), 2.00 - 1.91 (m, 4H, >CHCH2-), 1.62 - 1.22 (m, 96H, -CH2CH2CH2-,-CH2CH3), 0.87 (t, 12H, -CH2CH3). MS (ESI): m / z=1737.3 ([M+H] + )。 Example 11: Cationic Lipid E11-1 Replace the raw material S2-5 in Example 10 with raw material S3-5 (0.49 g, 0.8 mmol), and prepare according to the same reaction steps to obtain cationic lipid E11-1 (0.91 g). 1 1H NMR (400 MHz, CDCl3) δ: 7.06 - 6.99 (m, 4H, -CH=CHCH2-), 5.84 - 5.77 (m, 4H, -CH=CHCH2-), 4.25 (t, 4H, -C(=O)OCH2CH2O-), 4.14 - 4.04 (m, 16H, -C(=O)OCH2-), 3.67 - 3.62 (m, 4H, -C(=O)OCH2CH2O-), 3.55 - 3.49 (m, 4H, -OCH2CH2N<-), 3.26 - 3.22 (m, 2H, >NCH<), 3.20 (s, 4H, pip-CH2-), 2.78 - 2.70 (m, 4H, >NCH2-), 2.64 (s, 8H, pip-H), 2.40 - 2.25 (m, 10H; 4H, >CHCH2CH2-; 6H, >NCH3), 2.08 - 1.91 (m, 12H; 4H, >CHCH2-; 8H, -CH=CHCH2-), 1.62 - 1.22 (m, 56H, -CH2CH2CH2-,-CH2CH3), 0.86 (t, 12H, -CH2CH3). MS (ESI): m / z=1561.0 ([M+H]+ )。 Example 12: Cationic Lipid E12-1 Replace the raw material S2-5 in Example 10 with raw material S4-5 (0.55 g, 0.8 mmol), and prepare according to the same reaction steps to obtain cationic lipid E12-1 (1.00 g). 1 H NMR(400MHz,CDCl3)δ:4.25(t,4H,-C(=O)OCH2CH2O-),4.14-4.04(m,16H,-C(=O)OCH2-),3.67-3.62(m,4H,-C(=O)OCH2CH2O-),3.55-3.49(m,4H,-OCH2CH2N<-),3.28-3.22(m,2H,>NCH<),3.21(s,4H,pip-CH2-),2.78-2.70(m,4H,>NCH2-),2.66(s,8H,pip-H),2.27-2.20(m,26H;8H,-C≡CCH2CH2CH2OC(=O)-;4H,>CHCH2CH2-;8H,-CH2C(=O)O-;6H,>NCH3),2.17-2.10(m,8H,-C≡CCH2CH2CH2CH3),2.00-1.92(m,4H,>CHCH2-),1.84-1.76(m,8H,-C(=O)OCH2CH2CH2C≡C-),1.62-1.22(m,56H,-CH2CH2CH2-,-CH2CH3),0.88(t,12H,-CH2CH3). MS(ESI):m / z=1721.2([M+H] + )。 Example 13: Cationic Lipid E13-1 Replace the raw material S2-5 in Example 10 with raw material S5-2 (0.52 g, 0.8 mmol), and prepare according to the same reaction steps to obtain cationic lipid E13-1 (0.95 g). 11H NMR (400 MHz, CDCl3) δ: 5.45 - 5.26 (m, 16H, -CH=CH-), 4.25 (t, 4H, -C(=O)OCH2CH2O-), 4.14 - 4.04 (m, 8H, -C(=O)OCH2-), 3.83 - 3.78 (m, 2H, >NCH<), 3.67 - 3.62 (m, 4H, -C(=O)OCH2CH2O-), 3.55 - 3.49 (m, 4H, -OCH2CH2N<-), 3.22 (s, 4H, pip-CH2-), 2.85 - 2.70 (m, 14H; 2H, >CHCH2-; 8H, -CH=CHCH2CH=CH-; 4H, >NCH2-), 2.64 (s, 8H, pip-H), 2.60 - 2.53 (m, 2H, >CHCH2-), 2.36 (s, 6H, >NCH3), 2.03 - 1.97 (m, 16H, -CH=CHCH2-), 1.62 - 1.22 (m, 72H, -CH2CH2CH2-, -CH2CH3), 0.90 (t, 12H, -CH2CH3). MS (ESI): m / z=1629.3 ([M+H] + )。 Example 14: Cationic Lipid E14-1 Replace the raw material S2-5 in Example 10 with raw material S6-1 (0.55 g, 0.8 mmol), and prepare according to the same reaction steps to obtain cationic lipid E14-1 (1.00 g). 1 1H NMR (400 MHz, CDCl3) δ: 4.25 (t, 4H, -C(=O)OCH2CH2O-), 4.14 - 4.04 (m, 16H, -C(=O)OCH2-), 3.83 - 3.78 (m, 2H, >NCH<), 3.67 - 3.62 (m, 4H, -C(=O)OCH2CH2O-), 3.55 - 3.49 (m, 4H, -OCH2CH2N<-), 3.22 (s, 4H, pip-CH2-), 2.84 - 2.78 (m, 2H, >CHCH2-), 2.77 - 2.70 (m, 4H, >NCH2-), 2.66 (s, 8H, pip-H), 2.60 - 2.53 (m, 2H, >CHCH2-), 2.36 (s, 6H, >NCH3), 2.23 (t, 8H, -CH2C(=O)O-), 1.62 - 1.22 (m, 96H, -CH2CH2CH2-, -CH2CH3), 0.87 (t, 12H, -CH2CH3). MS (ESI): m / z=1709.3 ([M+H] + )。 Example 15: Cationic Lipid E15-1 Replace the raw material S2-5 in Example 10 with raw material S7-1 (0.48 g, 0.8 mmol), and prepare according to the same reaction steps to obtain cationic lipid E15-1 (0.89 g). 1 H NMR (400 MHz, CDCl3) δ: 7.06 - 6.99 (m, 4H, -CH=CHCH2-), 5.85 - 5.79 (m, 4H, -CH=CHCH2-), 4.25 (t, 4H, -C(=O)OCH2CH2O-), 4.14 - 4.04 (m, 16H, -C(=O)OCH2-), 3.67 - 3.62 (m, 4H, -C(=O)OCH2CH2O-), 3.55 - 3.49 (m, 4H, -OCH2CH2N<-), 3.83 - 3.78 (m, 2H, >NCH<), 3.24 (s, 4H, pip-CH2-), 2.84 - 2.79 (m, 2H, >CHCH2-), 2.78 - 2.70 (m, 4H, >NCH2-), 2.66 (s, 8H, pip-H), 2.60 - 2.53 (m, 2H, >CHCH2-), 2.36 (s, 6H, >NCH3), 2.10 - 1.91 (m, 8H, -CH=CHCH2-), 1.62 - 1.22 (m, 56H, -CH2CH2CH2-,-CH2CH3), 0.85 (t, 12H, -CH2CH3). MS (ESI): m / z=1533.0 ([M+H] + )。 Example 16: Cationic Lipid E16-1 Replace the raw material S2-5 in Example 10 with raw material S8-1 (0.54 g, 0.8 mmol), and prepare according to the same reaction steps to obtain cationic lipid E16-1 (0.98 g). 11H NMR (400 MHz, CDCl3) δ: 4.25 (t, 4H, -C(=O)OCH2CH2O-), 4.15 (t, 8H, -C(=O)OCH2CH2CH2C≡C-), 4.12 - 4.08 (m, 4H, >CHCH2C(=O)OCH2-), 4.05 (t, 4H, >CHC(=O)OCH2-), 3.83 - 3.78 (m, 2H, >NCH<), 3.67 - 3.62 (m, 4H, -C(=O)OCH2CH2O-), 3.55 - 3.49 (m, 4H, -OCH2CH2N<-), 3.25 (s, 4H, pip-CH2-), 2.85 - 2.79 (m, 2H, >CHCH2-), 2.78 - 2.70 (m, 4H, >NCH2-), 2.65 (s, 8H, pip-H), 2.60 - 2.53 (m, 2H, >CHCH2-), 2.36 (s, 6H, >NCH3), 2.22 - 2.27 (m, 8H, -C≡C(CH2)3OC(=O)CH2-), 2.27 - 2.20 (m, 8H, -C≡CCH2CH2CH2OC(=O)-), 2.17 - 2.10 (m, 8H, -C≡CCH2CH2CH2CH3), 1.84 - 1.25 (m, 64H, -CH2CH2CH2-, -CH2CH3), 0.90 (t, 12H, -CH2CH3). MS (ESI): m / z = 1694.1 ([M+H] + )。 Example 17: Cationic Lipid E17-1 The preparation process is as follows: Step a: Dissolve 4-bromobutyric acid (S17-2, 1.32 g, 3.6 mmol) in dichloromethane, then successively add DIPEA (0.46 g, 3.6 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 0.69 g, 3.6 mmol) and 1-hydroxybenzotriazole (HOBt, 0.49 g, 3.6 mmol), stir at room temperature for 10 minutes, then add S17-1 (0.24 g, 1.2 mmol) to the mixture, and react at room temperature for 12 h. After the reaction is completed, the reaction solution is washed twice with an appropriate amount of water, twice with 10% aqueous citric acid solution, and once with saturated brine. The organic phases are combined, dried over anhydrous magnesium sulfate, filtered, and the filtrate is concentrated. The crude product is purified by column chromatography to obtain S17-3 (1.26 g). Step b: Under nitrogen protection, dissolve compound S17-3 (0.83 g, 1.8 mmol) in acetonitrile (20 mL). Sequentially add S1-6 (0.53 g, 0.8 mmol) and DIPEA (0.23 g, 1.8 mmol) under slow stirring, and stir the reaction at room temperature for about 20 h. After the reaction is completed, concentrate the reaction solution, then dissolve it with dichloromethane, extract it successively with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution, combine the organic phases, dry with anhydrous magnesium sulfate, filter, concentrate the filtrate, and purify the crude product by column chromatography to obtain cationic lipid E17-1 (0.95 g). 1 H NMR(400MHz,CDCl3)δ:5.45-5.26(m,16H,-CH=CH-),4.17-4.00(m,8H,-C(=O)OCH2-),3.46-3.33(m,4H,-CH2NH-),3.27-3.22(m,2H,>NCH<),2.78(t,8H,-CH=CHCH2CH=CH-),2.71-2.64(m,4H,pip-CH2-),2.59-2.54(m,2H,>NCH2-),2.51-2.43(m,10H;2H,>NCH2-;8H,pip-H),2.41-2.35(m,4H,>CHCH2CH2-),2.25(s,6H,>NCH3),2.20-2.13(m,4H,-NHC(=O)CH2-),2.08-1.91(m,20H;4H,>CHCH2-;16H,-CH=CHCH2-),1.62-1.22(m,76H,-CH2CH2CH2-,-CH2CH3),0.88(t,12H,-CH2CH3). MS(ESI):m / z=1623.4([M+H] + )。 Example 18: Cationic lipid E18-1 The preparation process is as follows: Under nitrogen protection, dissolve compound S17-3 (0.83 g, 1.8 mmol) in acetonitrile (20 mL). Sequentially add S2-5 (0.56 g, 0.8 mmol) and DIPEA (0.23 g, 1.8 mmol) under slow stirring, and stir the reaction at room temperature for about 20 h. After the reaction is completed, concentrate the reaction solution, then dissolve it with dichloromethane, extract it successively with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution, combine the organic phases, dry with anhydrous magnesium sulfate, filter, concentrate the filtrate, and purify the crude product by column chromatography to obtain cationic lipid E18-1 (1.00 g). 11H NMR (400 MHz, CDCl3) δ: 4.14 - 4.03 (m, 16H, -C(=O)OCH2-), 3.46 - 3.33 (m, 4H, -CH2NH-), 3.27 - 3.23 (m, 2H, >NCH<), 2.71 - 2.64 (m, 4H, pip-CH2-), 2.59 - 2.54 (m, 2H, >NCH2-), 2.53 - 2.42 (m, 10H; 2H, >NCH2-; 8H, pip-H), 2.40 - 2.34 (m, 4H, >CHCH2CH2-), 2.30 (t, 8H, -CH2C(=O)O-), 2.25 (s, 6H, >NCH3), 2.20 - 2.13 (m, 4H, -NHC(=O)CH2-), 2.01 - 1.91 (m, 4H, >CHCH2-), 1.62 - 1.22 (m, 100H, -CH2CH2CH2-, -CH2CH3), 0.90 (t, 12H, -CH2CH3). MS(ESI): m / z=1703.3 ([M+H] + )。 Example 19: Cationic Lipid E19-1 Replace the raw material S2-5 in Example 18 with raw material S3-5 (0.49 g, 0.8 mmol), and prepare according to the same reaction steps to obtain cationic lipid E19-1 (0.89 g). 1 1H NMR (400 MHz, CDCl3) δ: 7.06 - 6.99 (m, 4H, -CH=CHCH2-), 5.84 - 5.79 (m, 4H, -CH=CHCH2-), 4.14 - 4.04 (m, 16H, -C(=O)OCH2-), 3.46 - 3.33 (m, 4H, -CH2NH-), 3.27 - 3.21 (m, 2H, >NCH<), 2.71 - 2.64 (m, 4H, pip-CH2-), 2.59 - 2.54 (m, 2H, >NCH2-), 2.53 - 2.42 (m, 10H; 2H, >NCH2-; 8H, pip-H), 2.40 - 2.25 (m, 10H; 4H, >CHCH2CH2-; 6H, >NCH3), 2.20 - 2.13 (m, 4H, -NHC(=O)CH2-), 2.09 - 1.90 (m, 12H; 4H, >CHCH2-; 8H, -CH=CHCH2-), 1.62 - 1.22 (m, 60H, -CH2CH2CH2-, -CH2CH3), 0.88 (t, 12H, -CH2CH3). MS(ESI): m / z=1527.1 ([M+H] + )。 Example 20: Cationic Lipid E20-1 Replace the raw material S2-5 in Example 18 with raw material S4-5 (0.55 g, 0.8 mmol), and prepare according to the same reaction steps to obtain cationic lipid E20-1 (0.99 g). 1 H NMR (400 MHz, CDCl3) δ: 4.14 - 4.04 (m, 16H, -C(=O)OCH2-), 3.46 - 3.33 (m, 4H, -CH2NH-), 3.29 - 3.22 (m, 2H, >NCH<), 2.71 - 2.64 (m, 4H, pip-CH2-), 2.61 - 2.43 (m, 12H; 2H, >NCH2-; 8H, pip-H), 2.27 - 2.21 (m, 26H; 8H, -C≡CCH2CH2CH2OC(=O)-; 4H, >CHCH2CH2-; 8H, -CH2C(=O)O-; 6H, >NCH3), 2.20 - 2.10 (m, 12H; 8H, -C≡CCH2CH2CH2CH3; 4H, -NHC(=O)CH2-), 2.00 - 1.92 (m, 4H, >CHCH2-), 1.84 - 1.76 (m, 8H, -C(=O)OCH2CH2CH2C≡C-), 1.62 - 1.22 (m, 60H, -CH2CH2CH2-, -CH2CH3), 0.87 (t, 12H, -CH2CH3). MS (ESI): m / z = 1687.2 ([M+H] + )。 Example 21: Cationic Lipid E21-1 Replace the raw material S2-5 in Example 18 with raw material S5-2 (0.52 g, 0.8 mmol), and prepare according to the same reaction steps to obtain cationic lipid E21-1 (0.94 g). 11H NMR (400 MHz, CDCl3) δ: 5.45 - 5.26 (m, 16H, -CH=CH-), 4.14 - 4.04 (m, 8H, -C(=O)OCH2-), 3.83 - 3.78 (m, 2H, >NCH<), 3.46 - 3.33 (m, 4H, -CH2NH-), 2.85 - 2.71 (m, 10H; 2H, >CHCH2-; 8H, -CH=CHCH2CH=CH-), 2.70 - 2.64 (m, 4H, pip-CH2-), 2.61 - 2.42 (m, 14H; 8H, pip-H; 2H, >CHCH2-; 4H, >NCH2-), 2.36 (s, 6H, >NCH3), 2.20 - 2.13 (m, 4H, -NHC(=O)CH2-), 2.03 - 1.97 (m, 16H, -CH=CHCH2-), 1.62 - 1.22 (m, 76H, -CH2CH2CH2-, -CH2CH3), 0.87 (t, 12H, -CH2CH3). MS (ESI): m / z = 1595.3 ([M+H] + )。 Example 22: Cationic Lipid E22-1 Replace the raw material S2-5 in Example 18 with raw material S6-1 (0.55 g, 0.8 mmol), and prepare according to the same reaction steps to obtain cationic lipid E22-1 (0.99 g). 1 1H NMR (400 MHz, CDCl3) δ: 4.14 - 4.04 (m, 16H, -C(=O)OCH2-), 3.83 - 3.78 (m, 2H, >NCH<), 3.46 - 3.33 (m, 4H, -CH2NH-), 2.84 - 2.78 (m, 2H, >CHCH2-), 2.71 - 2.64 (m, 4H, pip-CH2-), 2.61 - 2.41 (m, 14H; 8H, pip-H; 2H, >CHCH2-; 4H, >NCH2-), 2.36 (s, 6H, >NCH3), 2.23 (t, 8H, -CH2C(=O)O-), 2.20 - 2.13 (m, 4H, -NHC(=O)CH2-), 1.62 - 1.22 (m, 100H, -CH2CH2CH2-, -CH2CH3), 0.90 (t, 12H, -CH2CH3). MS (ESI): m / z = 1675.3 ([M+H] + )。 Example 23: Cationic Lipid E23-1 Replace the raw material S2-5 in Example 18 with the raw material S7-1 (0.48 g, 0.8 mmol), and prepare according to the same reaction steps to obtain the cationic lipid E23-1 (0.88 g). 1 H NMR (400 MHz, CDCl3) δ: 7.06 - 6.99 (m, 4H, -CH=CHCH2-), 5.84 - 5.80 (m, 4H, -CH=CHCH2-), 4.14 - 4.04 (m, 16H, -C(=O)OCH2-), 3.83 - 3.78 (m, 2H, >NCH<), 3.46 - 3.33 (m, 4H, -CH2NH-), 2.84 - 2.78 (m, 2H, >CHCH2-), 2.71 - 2.64 (m, 4H, pip-CH2-), 2.61 - 2.42 (m, 14H; 8H, pip-H; 2H, >CHCH2-; 4H, >NCH2-), 2.36 (s, 6H, >NCH3), 2.20 - 2.13 (m, 4H, -NHC(=O)CH2-), 2.09 - 1.92 (m, 8H, -CH=CHCH2-), 1.62 - 1.22 (m, 60H, -CH2CH2CH2-, -CH2CH3), 0.88 (t, 12H, -CH2CH3). MS(ESI): m / z=1499.1 ([M+H] + )。 Example 24: Cationic lipid E24-1 Replace the raw material S2-5 in Example 18 with the raw material S8-1 (0.54 g, 0.8 mmol), and prepare according to the same reaction steps to obtain the cationic lipid E24-1 (0.97 g). 11H NMR (400 MHz, CDCl3) δ: 4.14 - 4.04 (m, 16H, -C(=O)OCH2-), 3.83 - 3.78 (m, 2H, >NCH<), 3.46 - 3.33 (m, 4H, -CH2NH-), 2.84 - 2.78 (m, 2H, >CHCH2-), 2.71 - 2.64 (m, 4H, pip-CH2-), 2.63 - 2.42 (m, 14H; 8H, pip-H; 2H, >CHCH2-; 4H, >NCH2-), 2.36 (s, 6H, >NCH3), 2.27 - 2.23 (m, 16H; 8H, -C≡CCH2CH2CH2OC(=O)-; 8H, -CH2C(=O)O-), 2.20 - 2.10 (m, 12H; 8H, -C≡CCH2CH2CH2CH3; 4H, -NHC(=O)CH2-), 1.84 - 1.76 (m, 8H, -C(=O)OCH2CH2CH2C≡C-), 1.62 - 1.22 (m, 60H, -CH2CH2CH2-, -CH2CH3), 0.89 (t, 12H, -CH2CH3). MS (ESI): m / z = 1659.2 ([M+H] + )。 Example 25: Cationic Lipid E25-1 The preparation process is as follows: Step a: Dissolve N,N'-bis(2-hydroxyethyl)piperazine (S25-1, 0.52 g, 3.0 mmol) in acetonitrile (30 mL), add DIC (1.51 g, 12.0 mmol), then sequentially add DMAP (0.55 g, 4.5 mmol) and S17-2 (2.00 g, 12.0 mmol) to the solution. Stir the reaction mixture at room temperature overnight. After the reaction is completed, filter, concentrate the filtrate, dissolve the residue in dichloromethane (30 mL), and wash the resulting solution with water (10 mL * 2) and brine (30 mL * 1) in sequence. Combine the organic phases, dry with anhydrous magnesium sulfate, filter, concentrate, and purify the crude product by column chromatography to obtain S25-2 (1.32 g, 93.2%). Step b: Under nitrogen protection, dissolve compound S25-2 (0.83 g, 1.8 mmol) in acetonitrile (20 mL). Sequentially add S1-6 (0.53 g, 0.8 mmol) and DIPEA (0.23 g, 1.8 mmol) under slow stirring, and stir the reaction at room temperature for about 20 h. After the reaction is completed, concentrate the reaction solution, then dissolve it with dichloromethane, extract it successively with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution, combine the organic phases, dry with anhydrous magnesium sulfate, filter, concentrate the filtrate, and purify the crude product by column chromatography to obtain cationic lipid E25-1 (0.95 g). 1 H NMR (400 MHz, CDCl3) δ: 5.45 - 5.26 (m, 16H, -CH=CH-), 4.18 (t, 4H, pip-CH2CH2-), 4.17 - 4.00 (m, 8H, -C(=O)OCH2-), 3.28 - 3.22 (m, 2H, >NCH<), 2.77 (t, 8H, -CH=CHCH2CH=CH-), 2.66 - 2.42 (m, 20H; 4H, pip-CH2-; 8H, pip-H; 4H, -CH2(CH2)2N<; 4H, >NCH2-), 2.41 - 2.34 (m, 4H, >CHCH2CH2-), 2.25 (s, 6H, >NCH3), 2.08 - 1.91 (m, 20H; 4H, >CHCH2-; 16H, -CH=CHCH2-), 1.62 - 1.22 (m, 76H, -CH2CH2CH2-, -CH2CH3), 0.87 (t, 12H, -CH2CH3). MS (ESI): m / z=1625.3 ([M+H] + )。 Example 26: Cationic lipid E26-1 The preparation process is as follows: Under nitrogen protection, dissolve compound S25-2 (0.83 g, 1.8 mmol) in acetonitrile (20 mL). Sequentially add S2-5 (0.56 g, 0.8 mmol) and DIPEA (0.23 g, 1.8 mmol) under slow stirring, and stir the reaction at room temperature for about 20 h. After the reaction is completed, concentrate the reaction solution, then dissolve it with dichloromethane, extract it successively with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution, combine the organic phases, dry with anhydrous magnesium sulfate, filter, concentrate the filtrate, and purify the crude product by column chromatography to obtain cationic lipid E26-1 (0.99 g). 11H NMR (400 MHz, CDCl3) δ: 4.18 (t, 4H, pip-CH2CH2-), 4.15 - 4.02 (m, 16H, -C(=O)OCH2-), 3.25 - 3.22 (m, 2H, >NCH<), 2.66 - 2.42 (m, 20H; 4H, pip-CH2-; 8H, pip-H; 4H, -CH2(CH2)2N<; 4H, >NCH2-), 2.40 - 2.34 (m, 4H, >CHCH2CH2-), 2.31 (t, 8H, -CH2C(=O)O-), 2.25 (s, 6H, >NCH3), 2.00 - 1.90 (m, 4H, >CHCH2-), 1.62 - 1.22 (m, 100H, -CH2CH2CH2-, -CH2CH3), 0.89 (t, 12H, -CH2CH3). MS (ESI): m / z = 1705.3 ([M+H] + )。 Example 27: Cationic Lipid E27-1 Replace the raw material S2-5 in Example 26 with raw material S3-5 (0.49 g, 0.8 mmol), and prepare according to the same reaction steps to obtain cationic lipid E27-1 (0.89 g). 1 1H NMR (400 MHz, CDCl3) δ: 7.06 - 6.99 (m, 4H, -CH=CHCH2-), 5.82 - 5.79 (m, 4H, -CH=CHCH2-), 4.18 (t, 4H, pip-CH2CH2-), 4.14 - 4.04 (m, 16H, -C(=O)OCH2-), 3.27 - 3.21 (m, 2H, >NCH<), 2.66 - 2.42 (m, 20H; 4H, pip-CH2-; 8H, pip-H; 4H, -CH2(CH2)2N<; 4H, >NCH2-), 2.40 - 2.25 (m, 10H; 4H, >CHCH2CH2-; 6H, >NCH3), 2.09 - 1.91 (m, 12H; 4H, >CHCH2-; 8H, -CH=CHCH2-), 1.62 - 1.22 (m, 60H, -CH2CH2CH2-, -CH2CH3), 0.86 (t, 12H, -CH2CH3). MS (ESI): m / z = 1529.1 ([M+H] + )。 Example 28: Cationic Lipid E28-1 Replace the raw material S2-5 in Example 26 with raw material S4-5 (0.55 g, 0.8 mmol), and prepare according to the same reaction steps to obtain cationic lipid E28-1 (1.00 g). 1 H NMR (400 MHz, CDCl3) δ: 4.18 (t, 4H, pip-CH2CH2-), 4.14 - 4.04 (m, 16H, -C(=O)OCH2-), 3.27 - 3.23 (m, 2H, >NCH<), 2.66 - 2.42 (m, 20H; 4H, pip-CH2-; 8H, pip-H; 4H, -CH2(CH2)2N<; 4H, >NCH2-), 2.27 - 2.20 (m, 26H; 8H, -C≡CCH2CH2CH2OC(=O)-; 4H, >CHCH2CH2-; 8H, -CH2C(=O)O-; 6H, >NCH3), 2.17 - 2.10 (m, 8H, -C≡CCH2CH2CH2CH3), 2.00 - 1.91 (m, 4H, >CHCH2-), 1.84 - 1.76 (m, 8H, -C(=O)OCH2CH2CH2C≡C-), 1.62 - 1.22 (m, 60H, -CH2CH2CH2-, -CH2CH3), 0.88 (t, 12H, -CH2CH3). MS (ESI): m / z=1689.2 ([M+H] + )。 Example 29: Cationic Lipid E29-1 Replace the raw material S2-5 in Example 26 with raw material S5-2 (0.52 g, 0.8 mmol), and prepare according to the same reaction steps to obtain cationic lipid E29-1 (0.94 g). 11H NMR (400 MHz, CDCl3) δ: 5.45 - 5.26 (m, 16H, -CH=CH-), 4.18 (t, 4H, pip-CH2CH2-), 4.14 - 4.04 (m, 8H, -C(=O)OCH2-), 3.83 - 3.78 (m, 2H, >NCH<), 2.85 - 2.70 (m, 10H; 2H, >CHCH2-; 8H, -CH=CHCH2CH=CH-), 2.66 - 2.42 (m, 22H; 2H, >CHCH2-; 4H, pip-CH2-; 8H, pip-H; 4H, -CH2(CH2)2N<; 4H, >NCH2-), 2.36 (s, 6H, >NCH3), 2.03 - 1.97 (m, 16H, -CH=CHCH2-), 1.62 - 1.22 (m, 76H, -CH2CH2CH2-, -CH2CH3), 0.88 (t, 12H, -CH2CH3). MS (ESI): m / z=1597.3 ([M+H] + )。 Example 30: Cationic Lipid E30-1 Replace the raw material S2-5 in Example 26 with the raw material S6-1 (0.55 g, 0.8 mmol), and prepare according to the same reaction steps to obtain the cationic lipid E30-1 (0.98 g). 1 1H NMR (400 MHz, CDCl3) δ: 4.18 (t, 4H, pip-CH2CH2-), 4.14 - 4.02 (m, 16H, -C(=O)OCH2-), 3.75 (t, 2H, >NCH<), 2.84 - 2.76 (m, 2H, >CHCH2-), 2.66 - 2.42 (m, 18H; 2H, >CHCH2-; 4H, pip-CH2-; 8H, pip-H; 4H, -CH2(CH2)2N<), 2.35 - 2.25 (m, 18H; 8H, -CH2C(=O)O-; 6H, >NCH3; 4H, >NCH2-), 1.79 - 1.72 (m, 4H, -CH2CH2N<), 1.67 - 1.60 (m, 96H, -CH2CH2CH2-, -CH2CH3), 0.88 (m, 12H, -CH2CH3). MS (ESI): m / z=1678.2 ([M+H] + )。 Example 31: Cationic Lipid E31-1 Replace the raw material S2-5 in Example 26 with raw material S7-1 (0.48 g, 0.8 mmol), and prepare according to the same reaction steps to obtain cationic lipid E31-1 (0.88 g). 1 H NMR (400 MHz, CDCl3) δ: 7.06 - 6.99 (m, 4H, -CH=CHCH2-), 5.83 - 5.79 (m, 4H, -CH=CHCH2-), 4.18 (t, 4H, pip-CH2CH2-), 4.14 - 4.04 (m, 16H, -C(=O)OCH2-), 3.83 - 3.78 (m, 2H, >NCH<), 2.84 - 2.78 (m, 2H, >CHCH2-), 2.66 - 2.42 (m, 22H; 2H, >CHCH2-; 4H, pip-CH2-; 8H, pip-H; 4H, -CH2(CH2)2N<), 2.36 (s, 6H, >NCH3), 2.09 - 1.91 (m, 8H, -CH=CHCH2-), 1.62 - 1.22 (m, 60H, -CH2CH2CH2-, -CH2CH3), 0.88 (t, 12H, -CH2CH3). MS (ESI): m / z=1501.0 ([M+H] + )。 Example 32: Cationic Lipid E32-1 Replace the raw material S2-5 in Example 26 with raw material S8-1 (0.54 g, 0.8 mmol), and prepare according to the same reaction steps to obtain cationic lipid E32-1 (0.97 g). 11H NMR (400 MHz, CDCl3) δ: 4.18 (t, 4H, pip-CH2CH2-), 4.14 - 4.04 (m, 16H, -C(=O)OCH2-), 3.83 - 3.78 (m, 2H, >NCH<), 2.84 - 2.78 (m, 2H, >CHCH2-), 2.66 - 2.42 (m, 22H; 2H, >CHCH2-; 4H, pip-CH2-; 8H, pip-H; 4H, -CH2(CH2)2N<), 2.36 (s, 6H, >NCH3), 2.27 - 2.23 (m, 16H; 8H, -C≡CCH2CH2CH2OC(=O)-; 8H, -CH2C(=O)O-), 2.17 - 2.10 (m, 8H, -C≡CCH2CH2CH2CH3), 1.84 - 1.76 (m, 8H, -C(=O)OCH2CH2CH2C≡C-), 1.62 - 1.22 (m, 60H, -CH2CH2CH2-, -CH2CH3), 0.88 (t, 12H, -CH2CH3). MS (ESI): m / z = 1661.1 ([M + H] + )。 Example 33: Preparation of LNP-mRNA Pharmaceutical Composition and Testing of Its Physicochemical Properties Example 33.1: Preparation of LNP-mRNA Pharmaceutical Composition In this example, an LNP-mRNA pharmaceutical composition (LNP-mRNA) containing Fluc-mRNA was prepared. The phospholipids it contained were all DSPC, the sterol lipids were all cholesterol, and the polyethylene glycolated lipids were all PEG2k-DMG. The difference was the molar ratio of the cationic lipid to each lipid. The preparation method of LNP-mRNA is as follows: Step a: Pipette a certain amount of the stock solutions of the cationic lipid, DSPC, cholesterol, and polyethylene glycolated lipid. Dissolve the cationic lipid, DSPC, cholesterol, and polyethylene glycolated lipid in ethanol to obtain an ethanol-phase solution (the cationic lipids used in the control groups LCT-1, LCT-2, and LCT-3 were the cationic lipids of the prior art, and the cationic lipids of the experimental groups L-1 to L-34 were all the nitrogen-containing heterocyclic cationic lipids in Examples 1 - 32 of the present invention; among them, the lipid molar ratios used in LCT-1, LCT-2, L-1 to L-32 were 35:16:46.5:2.5, and the lipid molar ratios used in LCT-3, L-33 to L-34 were 50:10:38:1.5). Among them, the cationic lipid used in LCT-1 and LCT-3 is C-1, which is prepared by referring to the method disclosed in the patent literature CN115010681A. The cationic lipid used in LCT-2 is C-2, which is prepared by referring to the method disclosed in the patent literature US20220040308A1. The structures of C-1 and C-2 are as follows: C-1: C-2: Step b: Add Fluc-mRNA to a 10 - 50 mM citrate buffer (pH = 4) to obtain an aqueous solution. Step c: Mix the ethanol solution and the aqueous solution (1:3, v / v) to prepare LNP-mRNA, and wash it by ultrafiltration with DPBS multiple times to remove ethanol and free molecules. Finally, pass it through a 0.2 μm sterile filter and set aside. Example 33.2: Physicochemical property test of LNP-mRNA pharmaceutical composition Determination of encapsulation efficiency: Use the Quant-it Ribogreen RNA quantification kit to determine the encapsulation efficiency of the LNP-mRNA composition. The results show that the lipid compositions (L-1 to L-34) of the present invention have a high encapsulation efficiency for nucleic acid drugs (mRNA), all within the range of 80% - 96%, and most of the encapsulation efficiencies are within the range of 90% - 96%. The results indicate that the cationic lipids containing nitrogen heterocycles in each experimental group can encapsulate mRNA well, showing an encapsulation efficiency equivalent to or better than that of C-1 and C-2. There are also differences in the encapsulation efficiencies of the cationic lipids containing nitrogen heterocycles with different structures. Particle size determination: In this example, the particle size of LNP-mRNA is determined by dynamic light scattering (DLS). The measured LNP-mRNA has a high size uniformity, and its PDI is less than 0.3. The particle size of LNP-mRNA prepared from the lipid composition of the present application is within the range of 90 - 120 nm, meeting the requirements for the particle size of a gene carrier. Table 1: Summary table of the formulations of each lipid composition and the particle size and encapsulation efficiency of the LNP-mRNA prepared therefrom Example 34: Biological activity test of LNP-mRNA pharmaceutical composition (1) Serum stability evaluation The above LNP-mRNA was added to a medium containing 10% fetal bovine serum (FBS) and stirred at 37°C. Samples were taken at regular intervals to measure the particle size change of LNP-mRNA, and the serum stability of the nucleic acid drug formulation was analyzed by testing its particle size change. The experimental results showed that within 7 days, the particle size change of the experimental group was 0-13%, and that of the experimental group was 3-8%. These results indicate that the presence of the amino acid linker arm and the degradable group in the nitrogen heterocyclic branched cationic lipid of the present invention does not significantly affect the serum stability of the prepared LNP-nucleic acid drug composition. (2) Cytotoxicity evaluation Prepare DMEM high-glucose complete medium (containing 10% FBS). The samples (L-1 to L34 and L-CT1 to L-CT3) were respectively formulated into working solutions of 0.1, 0.15, 0.2, 0.25, and 0.3 μg / 100 μL using the complete medium and stored for later use. Take 293T cells in the logarithmic growth phase and inoculate them into 96-well plates at 7×103 / well and 100 μL / well. Both the control group and the experimental group were set with 6 replicates. After incubating in a 5% CO2, 37°C constant temperature incubator for 24 h, the original medium was retained. The control group was added with 100 μL / well of complete medium, and the sample group was added with 100 μL / well of the working solution. After continuing to incubate for 24 h, 100 μL / well of medium containing 10% CCK-8 was added and cultured in a 5% CO2, 37°C constant temperature incubator for 2 h. The absorbance value at 450 nm was detected by an enzyme-labeled instrument. Calculate the relative viability of the cells according to the following formula: Relative viability % = (absorbance value of the sample group - background absorbance value) / (absorbance value of the control group - background absorbance value) × 100%; where the background absorbance value is the absorbance of adding only the CCK-8 reagent and the medium. The experimental results showed that the LNP-mRNA drug composition prepared with the cationic lipid of the present invention did not produce obvious cytotoxicity at 5 concentration gradients, and the cell survival rate was greater than 95%. Specifically, for example, the result of the experimental group L-1 is shown in Figure 6. (3) Evaluation of in vitro transfection effect To investigate the mRNA transfection efficiency of each group of LNP-mRNA compositions prepared in Example 33 of the present invention at the cellular level, Luciferase bioluminescence was used for testing. The LNP-mRNA composition preparation was dissolved in the culture medium to prepare the required dose. Using 293T cells as the cell model, with an inoculation density of 6,000 cells / well, 100 μL / well of the cell suspension was inoculated into a 96-well plate with a black-edged transparent bottom. After inoculation, it was incubated in a cell culture incubator for 24 h, and then administered at a dose of 0.2 μg mRNA per well. The blank control group was added with the corresponding dose of free Fluc-mRNA. After 24 hours of transfection, the old culture medium was removed and replaced with a new culture medium containing the substrate of sodium D-luciferin (1.5 mg / mL), and after incubating for 5 minutes, the bioluminescence was detected using a microplate reader. The stronger the fluorescence, the more Fluc-mRNA was transported into the cytoplasm and translated into the corresponding fluorescent protein. The experimental results are shown in Table 2, where the relative fluorescence intensity value is the ratio of the fluorescence intensity value of each group to the fluorescence intensity of the blank control group. The results show that the LNP-mRNA pharmaceutical compositions prepared by the present invention all have excellent in vitro transfection effects, that is, the LNPs in the experimental groups are all effective nucleic acid delivery vectors. This may be because the cationic lipids of the present application contain multiple ionizable tertiary amine structures, and the transfection efficiency of the LNPs prepared therefrom is better than that of L-CT1, L-CT2, and L-CT3 groups prepared from nitrogen-containing heterocyclic cationic lipids in the prior art. Comparing the experimental groups L-2, L-3, and L-4, it can be seen that the saturation degree of the hydrophobic hydrocarbon tail chain affects the transfection efficiency of the LNP-mRNA pharmaceutical composition. Introducing unsaturated bonds can improve the fluidity of the membrane, thereby increasing cell uptake and improving the transfection efficiency of nucleic acids; comparing L-1 and L-5, L-2 and L-6, L-3 and L-7, L-4 and L-8, L-9 and L-13, L-10 and L-14, L-11 and L-15, L-12 and L-16, it can be seen that the carbon chain length between the tertiary amine and the linking group ester bond affects the ionizability of the tertiary amine. Within a certain range, the longer the carbon chain length, the stronger its ionizability and the higher the transfection efficiency. For example, the carbon chain lengths between the tertiary amine on glutamate of E1-1 and the three ester bonds are C4, C0, and C2 respectively, and the carbon chain length between the tertiary amine on glutamate of E5-1 and the ester bond is C4, C0, and C1 respectively, and the transfection efficiency of L-1 is higher than that of L-5; the type and number of degradable groups contained in the hydrophobic hydrocarbon tail chain also affect the transfection effect of the LNP-mRNA pharmaceutical composition. In some cases, increasing the number of degradable groups can improve the transfection efficiency. The influence of the type and number of degradable groups contained in the hydrophobic hydrocarbon tail chain on the performance of the LNP-mRNA pharmaceutical composition is relatively complex and further research is needed. In addition, LNP-mRNAs prepared with different molar ratios also showed certain differences. When preparing LNP-mRNA with a molar ratio of 35:16:46.5:2.5 (L-CT1) using cationic lipid C-1, its transfection efficiency was worse than that of the group with a molar ratio of 50:10:38:1.5 (L-CT3). This may be because only the piperazine ring in C-1 provides an effective ionizable tertiary amine and it only contains two linear hydrophobic tail chains. This structure is not conducive to forming a conical geometry, thus resulting in a lower transfection rate. When comparing L-1 and L-33, and L-2 and L-34, the transfection effects of the two groups of LNP-mRNAs with molar ratios prepared using cationic lipids E1-1 and E2-1 were equivalent or the group with a molar ratio of 35:16:46.5:2.5 was slightly better. This shows that the cationic lipids of the present invention can also exhibit excellent transfection effects with a lower molar ratio, which can greatly reduce the dosage of cationic lipids. Table 2: Results of cell transfection tests (4) Evaluation of in vivo transfection effect Lipid nanoparticles L-1 were delivered to 6-8-week-old female BALB / c mice by tail vein injection at a dose of 10 μg / mouse, and in vivo fluorescence imaging of the mice was performed at 6, 12, and 24 hours after administration. After imaging at the last time point, the mice were euthanized, and the main organs heart, liver, spleen, lung, and kidney (from left to right in the figure) were imaged. 0.2 mL of D-luciferin sodium (15 mg / mL) was intraperitoneally injected 10-15 min before imaging. The experimental results (Figure 7) showed that the lipid nucleic acid drug composition prepared with the cationic lipid of the present invention can achieve efficient in vivo delivery of nucleic acid drugs, and the LNP-mRNA drug composition delivered into the body was mainly distributed in the liver and spleen. The above are only the embodiments of the present invention, and thus do not limit the patent scope of the present invention. Any equivalent structural or equivalent process transformations made using the content of the specification of the present invention, or directly or indirectly applied in other related technical fields, are similarly included in the patent protection scope of the present invention. For those skilled in the art, without departing from the purpose and scope of the present invention and without the need for unnecessary experiments, the present invention can be implemented within a relatively wide range under equivalent parameters, concentrations, and conditions. Although the present invention gives specific embodiments, it should be understood that the present invention can be further improved. In short, according to the principle of the present invention, this application intends to include any changes, uses, or improvements to the present invention, including changes made using conventional techniques known in the art that are outside the scope disclosed in this application.

Claims

1. A cationic lipid, characterized in that, The structure is as shown in the general formula (1): or a salt, tautomer, stereoisomer, deuterated compound or solvate thereof; wherein Core is a nitrogen-containing heterocyclic nucleus; L is a divalent linking group L d , said L d is selected from -(CH2) tm -, -Z-, -(CH2) tm Z-, -Z(CH2) tm -, -Z(CH2) tm Z-, -(CH2) tm Z(CH2) tm -, -Z(CH2) tm Z(CH2) tm -, -(CH2) tm Z(CH2) tm Z- and -(CH2) tm Z(CH2) tm Z(CH2) tm -, any one of them, wherein tm is independently an integer from 1 to 12 each time it appears; Z is independently -C(=O)-, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -O-, -S-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -, -NR c C(=O)NR c -, -OC(=O)NR c -, -NR c C(=O)O-, -SC(=O)NR c -, and -NR c C(=O)S-, any one of them, wherein R c is independently H or C 1-12 alkyl; AA is a residue of aspartic acid, glutamic acid or a derivative of the foregoing amino acid; Each occurrence of B1 and B2 is independently a linking key or C 1-20 an alkylene group; Each occurrence of L1, L2, L3, and L4 is independently a linking bond or a divalent linking group L a ; said L a is selected from -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -NH-, -O(CH2) s O-, -S-, -S-S-, -C(=O)S-, -SC(=O)-, -NHC(=O)-, -C(=O)NH-, -NHC(=O)NH-, -OC(=O)NH-, -NR c C(=O)O-, -SC(=O)NH-, -NHC(=O)S-, -C(=S)-, -OC(=S)-, -C(=S)O-, -OC(=S)O-, -NHC(=S)-, -C(=S)NH-, -NHC(=S)NH-, -OC(=S)NH- and -NHC(=S)O-, where s is 1, 2, 3 or 4; L1 and L3 are not simultaneously a linking bond; L2 and L4 are not simultaneously a linking bond; Each occurrence of R1 and R2 is independently a C 5-30 hydrocarbyl group or a C 5-30 hydrocarbyl derivative; a and b are each independently 1 or 2; when the -B1-L1-R1 and / or -B2-L2-R2 fragment is derived from the amino terminus of an amino acid and its derivative, a and b are each independently 1 or 2; when the -B1-L1-R1 and / or -B2-L2-R2 fragment is derived from the carboxyl terminus of an amino acid and its derivative, a and b are each independently 1; when a and b are 2, the two -B1-L1-R1 and / or -B2-L2-R2 fragments are each independently the same or different; c is 2, 3 or 4.

2. The cationic lipid according to claim 1, wherein The Core is where n is 1 or 2; preferably, the Core is Most preferably, it is 3. The cationic lipid according to claim 1, wherein Said L is -(CH2) tm -, -(CH2) tm O-, -(CH2) tm C(=O)-, -(CH2) tm C(=O)O-, -(CH2) tm OC(=O)-, -(CH2) tm C(=O)NH-, -(CH2) tm NHC(=O)-, -(CH2) tm OC(=O)O-, -(CH2) tm NHC(=O)O-, -(CH2) tm OC(=O)NH-, -(CH2) tm NHC(=O)NH-, -C(=O)(CH2) tm C(=O)-, -C(=O)(CH2) tm C(=O)(CH2) tm -, -(CH2) tm O(CH2) tm -, -(CH2) tm C(=O)(CH2) tm -, -(CH2) tm C(=O)O(CH2) tm -, -(CH2) tm OC(=O)(CH2) tm -, -(CH2) tm C(=O)NH(CH2) tm -, -(CH2) tm NHC(=O)(CH2) tm -, -(CH2) tm OC(=O)O(CH2) tm -, -(CH2) tm NHC(=O)O(CH2) tm -, -(CH2) tm C(=O)O(CH2) tm O(CH2) tm -, -(CH2) tm NH-, -(CH2) tm O(CH2) tm NH-, -(CH2) tm OC(=O)NH(CH2) tm - and -(CH2) tm NHC(=O)NH(CH2) tm Any one of -, and the left end is connected to the nitrogen-containing heterocycle; preferably -(CH2) tm O-, -(CH2) tm NH-, -(CH2) tm C(=O)-, -(CH2) tm O(CH2) tm -, -(CH2) tm C(=O)O(CH2) tm -, -(CH2) tm OC(=O)(CH2) tm -, -(CH2) tm O(CH2) tm NH-, -(CH2) tm NHC(=O)(CH2) tm -, -(CH2) tm C(=O)O(CH2) tm O(CH2) tm Any one of -; preferably, L is any one of -CH2C(=O)-, -CH2C(=O)O(CH2)4-, -CH2C(=O)O(CH2)3-, -CH2C(=O)O(CH2)2O(CH2)2-, -(CH2)2O-, -(CH2)2NH-, -(CH2)2NHC(=O)(CH2)3-, -(CH2)2OC(=O)(CH2)3- and -(CH2)2O(CH2)2NH-, and the left end is connected to the nitrogen-containing heterocycle.

4. The cationic lipid according to claim 1, wherein The AA is wherein R a is independently, each time it appears, a linking group, H or C 1-6 alkyl, and the C 1-6 alkyl is preferably methyl, ethyl, propyl or isopropyl; t3 is 0 or 1; Or AA is In the case where one or two of the carbonyl groups are each independently capped with an oxygen atom or a secondary amine atom, it is selected from any one of the following structures: More preferably, AA is any of the following structures: Among them, R a is C 1-6 alkyl; Most preferably, AA is Or 5. The cationic lipid according to claim 1, wherein The B1 and B2 are any one of the following cases: Case (1): B1 and B2 are each independently C 1-20 an alkylene group, more preferably B1 and B2 are each independently C 2-10 an alkylene group; the C 2-10 alkylene group is preferably any one of ethylene, propylene, butylene, pentylene, hexylene, heptylene, and octylene; Case (2): One of B1 and B2 is a linking bond and the other is C 1-20 Alkylene; Case (3): B1 and B2 are both a linking bond; More preferably, B1 and B2 are selected from the foregoing Case (1) or Case (3).

6. The cationic lipid according to claim 1, wherein The L1 and L2 are any one of the following cases: Case (1): L1 and L2 are each independently L a ; Case (2): One of L1 and L2 is a connection key, and the other is L a ; Case (3): L1 and L2 are both a linking bond; Preferably, L1 and L2 are each independently a linking bond, -C(=O)-, -O-, -NH-, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -OC(=O)NH-, -NHC(=O)O-, -NHC(=O)- or -C(=O)NH-; More preferably, L1 and L2 are the same, and are both a linking bond, -O-, -NH-, -OC(=O)- or -C(=O)O-.

7. The cationic lipid according to claim 1, wherein Each occurrence of L3 and L4 is independently a linking bond, -O-, -NH-, -C(=O)- or -C(=O)O-; preferably, one of L3 and L4 is a linking bond, and the other is -O-, -NH-, -C(=O)-, -C(=O)O-; more preferably, L3 and L4 are the same and are selected from a linking bond, -O-, -NH-.

8. The cationic lipid according to claim 1, wherein The R1 and R2 are each independently C 5-30 linear hydrocarbon group, C 5-30 branched hydrocarbon group or C 5-30 hydrocarbon derivative, and the C 5-30 hydrocarbon derivative is represented as The linear hydrocarbon group and the branched hydrocarbon group are each independently substituted or unsubstituted, and the substitution is preferably by C 1-6 alkyl group, halogen or hydroxyl group; The straight-chain hydrocarbon group is a straight-chain alkyl group, a straight-chain alkenyl group or a straight-chain alkynyl group; more preferably, it is a C 5-25 straight-chain hydrocarbon group; The branched hydrocarbon group is a branched alkyl group, a branched alkenyl group or a branched alkynyl group, and each independently represents as Among them, t is an integer from 0 to 12, t1 and t2 are each independently an integer from 0 to 5, t3 and t4 are each independently 0 or 1, and t1, t2, t3, and t4 are not all 0 at the same time; R e and R f are each independently any one of C 1-15 alkyl, C 2-15 alkenyl, and C 2-15 alkynyl; R e and R f are more preferably each independently selected from any one of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, vinyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl, nonenyl, decenyl, ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl, nonynyl, and decynyl; R e and R f are more preferably each independently selected from any one of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, and decyl.

9. The cationic lipid according to claim 8, wherein The R1 and R2 are any one of the following cases: Case (1): R1 and R2 are each independently C 5-30 a linear hydrocarbon group; Case (2): One of R1 and R2 is a C 5-30 linear hydrocarbon group, and the other is a C 5-30 branched hydrocarbon group Case (3): R1 and R2 are each independently C 5-30 branched hydrocarbon group Case (4): R1 and R2 are each independently Case (5): One of R1 and R2 is C 5-30 a linear hydrocarbon group or C 5-30 a branched hydrocarbon group Another one is R1 and R2 satisfying the above conditions are further preferably each independently selected from any one of the following structures:

10. The cationic lipid according to any one of claims 1-9, characterized in that, The -B1-L1-R1 and -B2-L2-R2 segments are each independently selected from any one of the following structures each time they appear:

11. The cationic lipid according to claim 1, wherein The structure of the cationic lipid satisfies any one of the following general formulas: wherein, t3 is 0 or 1; R a is H or C 1-6 alkyl; L1, L2, L3, L4, B1, and B2 are not a linking bond; Preferably, in formula (2-A), formula (2-B), and formula (2-C), L is -(CH2) tm Z(CH2) tm - or -(CH2) tm Z(CH2) tm Z(CH2) tm -, where Z is independently, each time it appears, any one of -OC(=O)-, -C(=O)O-, -OC(=O)O-, -NHC(=O)-, -C(=O)NH-, -NHC(=O)O-, -OC(=O)NH-, -O-, -NH-; more preferably, L is -(CH2) tm O-, -(CH2) tm NH-, -(CH2) tm C(=O)-, -(CH2) tm O(CH2) tm -、-(CH2) tm C(=O)O(CH2) tm -、-(CH2) tm OC(=O)(CH2) tm -、-(CH2) tm O(CH2) tm NH-、-(CH2) tm NHC(=O)(CH2) tm -、-(CH2) tm C(=O)O(CH2) tm O(CH2) tm - any one of; More preferably, the structure of the cationic lipid satisfies any of the following general formulas: wherein, * represents the same structure as in [], and Z in Formula (3-1) to Formula (3-24) is -C(=O)O-, -OC(=O)-, -C(=O)NH-, -NHC(=O)-, -OC(=O)NH- or -NHC(=O)O-; In all the foregoing general formulas, preferably, L1 and L2 are each independently -C(=O)-, -O-, -NH-, -C(=O)O-, -OC(=O)-, -OC(=O)O-, -C(=O)NH-, -NHC(=O)-, -OC(=O)NH-, -NHC(=O)O-; more preferably, L1 and L2 are each independently -O-, -NH-, -C(=O)-, -C(=O)O-, -OC(=O)-, -OC(=O)O-; Preferably, the structure of the cationic lipid satisfies any one of formulas (3-1) to (3-6), where Z is -C(=O)O-, -OC(=O)-, -C(=O)NH-, or -NHC(=O)-; L1 and L2 are each independently any one of -O-, -NH-, -C(=O)O-, -OC(=O)-, -OC(=O)O-; L3 and L4 are each independently -O- or -NH-.

12. The cationic lipid according to claim 1, wherein Its structure is selected from any of the following structures:

13. A lipid composition, characterized in that, Containing the cationic lipid described in any one of claims 1-12.

14. The lipid composition according to claim 13, wherein It further contains one or more of phospholipids, sterol lipids, and polyethylene glycolated lipids; selected from any one of the following situations: Situation (1): It further contains phospholipids; Situation (2): It further contains sterol lipids; Situation (3): It further contains polyethylene glycolated lipids; Situation (4): It further contains phospholipids and sterol lipids; Situation (5): It further contains phospholipids and polyethylene glycolated lipids; Situation (6): It further contains sterol lipids and polyethylene glycolated lipids; Situation (7): It further contains phospholipids, sterol lipids, and polyethylene glycolated lipids; Situation (8): It further contains phospholipids, sterol lipids, polyethylene glycolated lipids, and another cationic lipid; Situation (9): It further contains phospholipids, sterol lipids, polyethylene glycolated lipids, and anionic lipids; More preferably, it also contains three lipids, namely phospholipids, sterol lipids, and polyethylene glycolated lipids, simultaneously.

15. The lipid composition according to claim 14, characterized in that, The phospholipids are selected from any one of 1,2-dilinoleoyl-sn-glycero-3-phosphocholine, 1,2-dimyristoyl-sn-glycero-phosphocholine, 1,2-dioleoyl-sn-glycero-3-phosphocholine, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, 1,2-distearoyl-sn-glycero-3-phosphocholine, 1,2-dielaidoyl-sn-glycero-phosphocholine, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, 1,2-di-O-octadecenoyl-sn-glycero-3-phosphocholine, 1-oleoyl-2-cholesteryl succinyl-sn-glycero-3-phosphocholine, 1-hexadecyl-sn-glycero-3-phosphocholine, 1,2-dilinolenoyl-sn-glycero-3-phosphocholine, 1,2-diarachidonoyl-sn-glycero-3-phosphocholine, 1,2-didocosahexaenoyl-sn-glycero-3-phosphocholine, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, 1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, 1,2-dilinoleoyl-sn-glycero-3-phosphoethanolamine, 1,2-dilinolenoyl-sn-glycero-3-phosphoethanolamine, 1,2-diarachidonoyl-sn-glycero-3-phosphoethanolamine, 1,2-didocosahexaenoyl-sn-glycero-3-phosphoethanolamine, 1,2-dioleoyl-sn-glycero-3-phospho-rac-(1-glycerol) sodium salt, dioleoyl phosphatidylserine, dipalmitoyl phosphatidylglycerol, palmitoyl oleoyl phosphatidylethanolamine, distearoyl-phosphatidylethanolamine, dipalmitoyl phosphatidylethanolamine, dimyristoyl phosphoethanolamine, 1-stearoyl-2-oleoyl-stearoylethanolamine, 1-stearoyl-2-oleoyl-phosphatidylcholine, sphingomyelin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidic acid, palmitoyl oleoyl phosphatidylcholine, lysophosphatidylcholine and lysophosphatidylethanolamine and their combinations; or the steroid lipids are selected from any one of cholesterol, coprosterol, sitosterol, ergosterol, campesterol, stigmasterol, brassicasterol, tomatine, ursolic acid, α-tocopherol and their combinations; Or the polyethylene glycolated lipid is selected from polyethylene glycol-1,2-dimyristoyl glycerol, polyethylene glycol-distearoyl phosphatidylethanolamine, PEG-cholesterol, polyethylene glycol-diacylglycerol, polyethylene glycol-dialkoxypropyl, specifically including any one of polyethylene glycol 500-dipalmitoyl phosphatidylcholine, polyethylene glycol 2000-dipalmitoyl phosphatidylcholine, polyethylene glycol 500-distearoyl phosphatidylethanolamine, polyethylene glycol 2000-distearoyl phosphatidylethanolamine, polyethylene glycol 500-1,2-dioleoyl phosphatidylethanolamine, polyethylene glycol 2000-1,2-dioleoyl phosphatidylethanolamine, and polyethylene glycol 2000-2,3-dimyristoyl glycerol and its compositions; Or the structure of the polyethylene glycolated lipid is selected from any one of the following structural formulas and their compositions: Wherein, n1 is an integer from 20 to 250; Or the other cationic lipid is selected from any one of 1,2-dioleoyl-3-trimethylammonium-propane (methyl sulfate), 1,2-bis(octadecenoxy)-3-methylammonium propane chloride, 1-[2-(oleoyloxy)ethyl]-2-oleyl-3-(2-hydroxyethyl)imidazoline chloride, 1,2-dioleoyl-3-dimethylamino-propane, 2,3-bis(tetradecanoyloxy)propyltrimethylammonium chloride, didodecyldimethylammonium chloride, didodecyldimethylammonium bromide, N,N-dioleyl-N,N-dimethylammonium chloride, N-(4-carboxybenzyl)-N,N-dimethyl-2,3-bis(oleoyloxy)propan-1-ammonium, 3,6-bis{4-[bis(2-hydroxydodecyl)amino]butyl}piperazine-2,5-dione, 1,1'-((2-(4-(2-((2-(bis(2-hydroxydodecyl)amino)ethyl)(2-hydroxydodecyl)amino)ethyl)piperazin-1-yl)ethyl)azanediyl)bis(dodecan-2-ol), 4-(N,N-dimethylamino)butyric acid (dilinoleoyl) methyl ester, 1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine, ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate), 8-[(2-hydroxyethyl)(6-oxo-6-(undecyloxy)hexyl)amino]octanoic acid (nonadec-9-yl) ester, and ((2-(2-hydroxyethoxy)ethyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate) and its compositions; Or the anionic lipid is selected from any one of 1,2-dioleoyl-sn-glycero-3-phosphate sodium salt, 1,2-dimyristoyl-sn-glycero-3-phosphate sodium salt, bis(monooleoylglycerol) phosphate ammonium salt, and cardiolipin and its compositions.

16. The lipid composition according to any one of claims 14 - 15, characterized in that, Containing 20-80% of cationic lipid, 5-16% of phospholipid, 25-55% of steroid lipid, and 0.5-10% of polyethylene glycolated lipid, and the percentages are the molar percentages of each lipid in the total lipid in the solution containing the solvent.

17. The lipid composition according to claim 16, wherein, The molar percentage of the cationic lipid in the total lipids in the solution containing the solvent is 30 - 65%; more preferably any one of 35%, 40%, 45%, 46%, 47%, 48%, 49%, 50%, 55%; or the molar percentage of the phospholipid in the total lipids in the solution containing the solvent is 7.5 - 16%; more preferably any one of 8%, 9%, 10%, 11%, 12%, 16%; or the molar percentage of the steroid lipid in the total lipids in the solution containing the solvent is 35 - 50%, more preferably any one of 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%; or the molar percentage of the polyethylene glycolated lipid in the total lipids in the solution containing the solvent is 0.5 - 5%; preferably 1 - 3%; more preferably any one of 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2.0%, 2.5%.

18. A lipid pharmaceutical composition, characterized in that, Containing the lipid composition and the drug according to any one of claims 13 - 17, the drug being selected from any one of nucleic acid drugs, gene vaccines, anti-tumor drugs, small molecule drugs, polypeptide drugs or protein drugs.

19. The lipid pharmaceutical composition according to claim 18, wherein The nucleic acid drug is selected from any one of RNA, DNA, antisense nucleic acid, plasmid, interfering nucleic acid, aptamer, antagomir and ribozyme, and the RNA is selected from any one of mRNA, saRNA, circRNA, miRNA and siRNA; preferably the nucleic acid drug is any one of DNA, mRNA, miRNA and siRNA.

20. The lipid pharmaceutical composition according to any one of claims 18-19, characterized in that, The pharmaceutical composition is used as a drug and is selected from any one of the following drugs: anti-tumor agent, antiviral agent, anti-fungal agent and vaccine.

21. A lipid pharmaceutical composition preparation, characterized in that, Containing the lipid pharmaceutical composition according to claim 20 and a pharmaceutically acceptable diluent or excipient, the diluent or excipient being preferably any one of deionized water, ultrapure water, phosphate buffer solution and physiological saline, more preferably phosphate buffer solution or physiological saline, and most preferably physiological saline.

22. A liposome or lipid nanoparticle, characterized in that, Containing the lipid composition according to any one of claims 13 - 17.

23. The liposome or lipid nanoparticle according to claim 22, wherein The lipid nanoparticle is an LNP-drug composition, an LPP-drug composition or a PNP-drug composition; preferably an LNP-drug composition; more preferably an LNP-nucleic acid drug composition; more preferably an LNP-mRNA drug composition.

Images