Cationic lipid comprising nitrogen-containing heterocycle and glycine

Abstract

The present invention provides a glycine-containing cationic lipid. The structure of the glycine-containing cationic lipid is shown as general formula (1-A), wherein the definition of each symbol is consistent with that in the description. The glycine-branched cationic lipid has a nitrogen-containing heterocycle as a central branched core, has glycine as a secondary branched core, and has a saturated or unsaturated hydrocarbon group as a tail chain, and has the advantages of low toxicity, low immunogenicity, and high biocompatibility. Glycine contained in the novel cationic lipid of the present invention can provide a tertiary amine structure while serving as the secondary branched core, and form a multi-stage tertiary amine structure together with the nitrogen-containing heterocycle central core, increasing the number of tertiary amines capable of being ionized to produce positive charges. When preparing an LNP, the amount of cationic lipid used is less, which is safer and improves the translation efficiency of nucleic acids.

Description

A cationic lipid containing a nitrogen heterocycle and glycine Technical Field The present invention belongs to the field of drug delivery, and particularly relates to a cationic lipid containing a nitrogen heterocycle and glycine as a pharmaceutical carrier, a lipid composition containing the cationic lipid, a lipid drug composition and its preparation and application. Background Art Bioactive substances such as small molecule drugs, polypeptides, proteins and nucleic acids, especially nucleic acid drugs, are difficult to be effectively delivered into cells because they are easily degraded by nucleases and have a short half-life. Although chemical modification can significantly improve the stability of nucleic acids and avoid immune recognition, the space for chemical modification is limited, so a delivery system is usually required to achieve the effective delivery of nucleic acid drugs. The delivery system can improve the effectiveness and safety of nucleic acid drug therapy. Currently, lipid nanoparticles (LNPs) are the most commonly used nucleic acid drug delivery system. Lipid nanoparticles formed by cationic lipids and other lipid components (such as cholesterol, phospholipids, PEGylated lipids) and nucleic acid drugs can avoid the degradation of nucleic acids in plasma and promote the cellular uptake of nucleic acids. In the LNP delivery system, the nucleic acid structure, the cationic lipid structure and each lipid component are crucial for the effectiveness of the delivery system. In particular, the cationic lipid with the highest molar ratio significantly affects the effectiveness of the delivery system. Although mature cationic lipids such as MC3, SM102 and ALC-0315 have been applied in the prior art, there is still a need in the art to develop other cationic lipids that can be used to deliver nucleic acids, so as to achieve better delivery effects, such as protecting nucleic acids from being degraded and cleared in serum, having good tolerance, providing a sufficient therapeutic index, etc. Although the prior art has disclosed cationic lipids branched with nitrogen heterocycles, such as the compounds disclosed in CN115010681A and US20220040308A1, they do not contain an amino acid (such as glycine) linker, or do not contain a degradable group, or the number of degradable groups contained is limited, and cannot meet the requirements of all delivery systems. Therefore, there is still a need in the art to develop novel cationic lipids containing a nitrogen heterocycle and an amino acid (such as glycine) linker. Summary of the Invention The present invention provides a novel cationic lipid containing a nitrogen heterocycle and glycine, 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 as shown in the general formula (1-A): 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 (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 -, where 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-, -NH-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c (=O)-, -NR c C(=O)NR c (=O)-, -OC(=O)NR c (=O)-, -NR c C(=O)O-, -SC(=O)NR c (=O)- and -NR c C(=O)S- each time it appears, where R c is independently H or C 1-12 alkyl each time it appears; p is an integer from 1 to 4; B1 and B2 are independently a linking bond or C 1-20 alkylene each time they appear; L1, L2, L3, and L4 are independently a linking bond or a divalent linking group -(CH2) tn L a (CH2) tn (CH2) aSelected from -OC(=O)-, -C(=O)O-, -OC(=O)O-, -CH(OH)-, -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-; wherein s is 1, 2, 3 or 4; tn is independently an integer from 0 to 12 each time it appears; 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; R1 and R2 are each independently a C 5-30 hydrocarbyl group or a C 5-30 hydrocarbyl derivative; c is 2, 3 or 4. The present invention also provides a lipid composition, and the embodiment is as follows: A lipid composition containing a cationic lipid having the structure shown in formula (1-A). The present invention also provides a lipid drug composition, and the embodiment is as follows: A lipid drug composition containing a lipid composition and a drug, and the lipid composition contains a cationic lipid having the structure shown in formula (1-A), 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 lipid drug composition preparation, and the embodiment is 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 embodiment is 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-A). 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 (such as glycine or a glycine 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 a negatively charged drug or nucleic acid through electrostatic interaction, thereby effectively delivering the nucleic acid into cells. In addition, the present invention uses an amino acid or an amino acid derivative with good biocompatibility as the linker arm, further improving the biocompatibility of the cationic lipid. Moreover, the amino acid or amino acid biological raw materials are simple and easy to obtain, can be obtained naturally or synthesized simply, and have the advantages of simplicity, safety, and cost savings in production. The amino acid moiety 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-level tertiary amine structure, increasing the number of tertiary amines that can ionize positive charges. When preparing LNP, less cationic lipid is used, which is safer and improves the translation efficiency of nucleic acids. 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 being unable to fully exert their effects. 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 exhibit higher transfection efficiency and lower cytotoxicity. Brief 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 E13-1 prepared in Example 13. Figure 3 is the 1 1H NMR spectrum of the cationic lipid E14-1 prepared in Example 14. Figure 4 is the 1 1H NMR spectrum of the cationic lipid E25-1 prepared in Example 25. Figure 5 is the 1 1H NMR spectrum of the cationic lipid E28-1 prepared in Example 28. Figure 6 shows the high performance liquid chromatography (HPLC) test results of the cationic lipid E13-1 prepared in Example 13. Figure 7 is the mass spectrometry (MS) of the cationic lipid E13-1 prepared in Example 13. Figure 8 shows the cytotoxicity test results of the LNP-mRNA pharmaceutical composition L-15 prepared in Example 47. Figure 9 shows the imaging results after injection of the LNP-mRNA pharmaceutical composition L-15 prepared in Example 47 into mice. Embodiments Term Explanation In the present invention, unless otherwise described, all technical and scientific terms used herein have the same meaning as 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 event of any conflict between the description and interpretation of any term herein and any document incorporated herein by reference, the following description and interpretation of the term shall prevail. In the present invention, when the structure involved has isomers, without special designation, any one of the isomers may be used. 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 of this interval, and this 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, the 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 is generally 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 "comprising", "including" and "containing" and similar expressions shall be construed in an open and inclusive sense as "including but not limited to" in this specification and the claims. In the present invention, when two or more objects are "each independently preferably", in the case of having 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 kind of preference, 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 in different groups, they can each independently be any option in the definition, but also means that when they occur 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- and any one of them, wherein, R c each independently at each occurrence being a hydrogen atom or a C 1-12 alkyl", in the group "-NR c C(=O)NR c -", the two Rs c each independently being a hydrogen atom or a 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., without special limitation, when it connects to other groups, either of the two connecting ends can be selected. For example, when an amide bond is used as the divalent linking group between GroupA and GroupB, it can be GroupA-C(=O)NH-GroupB or GroupB-NHC(=O)-GroupA. In the present invention, when the end groups of the linking group in the structural formula are liable to be confused with the substituents contained in the linking group, to label the positions in the linking group where other groups are linked. For example, in the structural formula , the are used to label the two positions in the divalent linking group where other groups are linked. The above two structural formulas respectively represent -CH(CH2CH2CH3)2- and -CH2CH2CH(CH3)2-CH2CH2-. In the present invention, the number range of carbon atoms in a group is marked in subscript form at the subscript position of C, indicating the number of carbon atoms in the group. 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 selected from any alkylene having the number of carbon atoms within the range indicated by the subscript, that is, it can be selected from C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 any one of the alkylene. In the present invention, unless otherwise specified, the subscripts marked in interval form all represent any integer that can be selected within the range, and this range includes both endpoints. In the present invention, "group" can be called "bond" without changing the meaning. For example, the ether group (-O-) can also be called an ether bond, and the ester group (-OC(=O)- or -C(=O)O-) can also be called an ester bond. In the present invention, the "carbon chain length" between two groups refers to the shortest number of carbons 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 called C2), and the carbon chain length between the two ester bonds of -OC(=O)CH2CH2OCH2CH2OC(=O)- is C4 (which can also be called C4). In the present invention, the heteroatoms are not particularly limited and include but are not limited to O, S, N, P, Si, F, Cl, Br, I, B, etc. In the present invention, the heteroatom used for substitution is called a "substituting atom", and any group used for substitution is called a "substituent". In the present invention, "substituted" means that at least one hydrogen atom in any of the above groups (e.g., aliphatic hydrocarbon group, hydrocarbon group, alkyl group or 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; oxo group (=O); hydroxyl group (-OH); alkoxy group (-OR d , where R d is C 1-12 alkyl); carboxyl group (-COOH); amine group (-NR c R c , and two R c are each independently H, C 1-12 alkyl); C 1-12 alkyl and cycloalkyl. In some embodiments, the substituent is C 1-12 alkyl. In other embodiments, the substituent is cycloalkyl. 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 an alkoxy 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" (e.g., optionally substituted) means that the subsequent described situation or event may or may not occur, and this 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 this description includes substituted hydrocarbon groups and unsubstituted hydrocarbon groups. In the present invention, for a compound or a group, it can be both substituted and hybridized at the same time. For example, a nitro phenyl group replaces a hydrogen atom, or -CH2-CH2-CH2- is replaced by -CH2-S-CH(CH3)-. In the present invention, a "linking bond" only serves as a connection and does not contain any atoms. When a certain group is defined as a linking bond, it also means that this group may not exist. In the present invention, a "group" contains at least 1 atom and refers to a radical formed by a compound losing one or more atoms. Relative to a compound, the group formed after losing a partial group is also called a residue. The valence state of a group is not particularly limited. By way of example, it can be divided into monovalent groups, divalent groups, trivalent groups, tetravalent groups,..., 100-valent groups, etc. Among them, groups with a valence state greater than or equal to 2 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, hydrocarbons are classified into two types, aliphatic hydrocarbons and aromatic hydrocarbons, according to the type of hydrocarbon group. Hydrocarbons that do not contain a benzene ring or any structure in which the benzene ring is substituted by a hydrocarbon group are defined as aliphatic hydrocarbons. Hydrocarbons that contain at least one benzene ring or a benzene ring substituted by a hydrocarbon group are defined as aromatic hydrocarbons. And aromatic hydrocarbons can contain aliphatic hydrocarbon group structures, such as toluene, diphenylmethane, indane, etc. In the present invention, according to the saturation situation, hydrocarbons are classified 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, and without limitation, include 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 limitation on the structure of hydrocarbons, which can be in the form of a straight-chain structure without side groups, a branched-chain structure with side groups, 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 groups, a branched-chain structure with side groups, 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 groups and a branched-chain structure with side groups. 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, "hydrocarbon group" refers to the 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 alkylene groups), trivalent hydrocarbon groups (losing three hydrogen atoms), and so on. By analogy, when losing n hydrogen atoms, the valence state of the formed hydrocarbon group is n. In the absence of a special designation, the hydrocarbon group in the present invention specifically refers to a monovalent hydrocarbon group. Unless otherwise expressly 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, or from saturated hydrocarbons or unsaturated hydrocarbons, or from straight-chain hydrocarbons, branched-chain hydrocarbons or cyclic hydrocarbons, or from hydrocarbons or heterohydrocarbons, etc. From the perspective of saturation, for example, it can be derived from alkanes, alkenes, alkynes, dienes, etc.; for cyclic hydrocarbons, 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 alicyclic heterocyclic hydrocarbons or aromatic heterocyclic hydrocarbons. In the present invention, "aliphatic hydrocarbon group" refers to the residue formed after an aliphatic hydrocarbon loses at least one hydrogen atom. In the absence of a special designation, the aliphatic hydrocarbon group in the present invention specifically refers to a monovalent aliphatic hydrocarbon group. Aliphatic hydrocarbon groups include saturated aliphatic hydrocarbon groups and unsaturated aliphatic hydrocarbon groups. Unless otherwise expressly stated in this specification, the aliphatic hydrocarbon group is optionally substituted. In the present invention, "alkyl" refers to a hydrocarbon group formed from an alkane. Without special specification, 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 either n-propyl or isopropyl, and propylene refers to any one of 1,3-propylene, 1,2-propylene, and isopropylene. Unless otherwise explicitly stated in this specification, the alkyl group is optionally substituted. In the present invention, "unsaturated hydrocarbon group" refers to a hydrocarbon group formed by an unsaturated hydrocarbon losing a hydrogen atom. The hydrocarbon group formed by an unsaturated hydrocarbon losing a hydrogen atom on an unsaturated carbon can be classified into alkenyl, alkynyl, diene group, etc. In the present invention, "alkenyl" refers to a straight-chain or branched-chain hydrocarbon group containing at least one carbon-carbon double bond formed by an alkene losing a hydrogen atom at any position. For example, "C 2-15 alkenyl" means a straight-chain or branched-chain alkenyl group containing 2 - 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 explicitly stated in this specification, the alkenyl group is optionally substituted. In the present invention, "alkynyl" refers to a straight-chain or branched-chain hydrocarbon group containing at least one carbon-carbon triple bond formed by an alkyne losing a hydrogen atom at any position. For example, "C 2-15 alkynyl" means a straight-chain or branched-chain alkynyl group containing 2 - 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 explicitly stated in this specification, the alkynyl group is optionally substituted. In the present invention, "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 (C 1-24 subhydrocarbon group) having one to twenty-four carbon atoms, a subhydrocarbon group (C 1-12 subhydrocarbon group) having one to twelve carbon atoms. Specifically, for example, methylene, ethylene, propylene, n-butylene, vinylidene, propenylene, n-butylene, propynylene, n-butynylene, etc. Unless otherwise explicitly stated in this specification, the subhydrocarbon group 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 explicitly stated in this specification, the alkylene group 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 general formula compound components 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" Mn. 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" which indicates 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 the percentage, "about" generally means ±0.5%. In the present invention, "stable existence" and "degradability" of a group are a pair of relative concepts. For detailed examples of groups that can stably exist and groups that can be degraded, see section

[0134] -

[0145] 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 basic conditions, and the most commonly used are the ammonolysis of NH3 / MeOH and the methanolysis catalyzed by methoxide anion; benzyl can be easily removed by palladium-catalyzed hydrogenolysis at room temperature in a neutral solution, or 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 - ) in a tetrahydrofuran solution, or can also be removed 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, the tert-butyl group can be removed under mild acidic conditions, and the benzyl group can be removed by hydrogenolysis. The reagent for removing the carboxyl protecting group is selected from TFA, H2O, LiOH, NaOH, KOH, MeOH, EtOH and combinations thereof, preferably a combination of TFA and H2O, a combination of LiOH and MeOH, or a 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 protecting groups for 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-fluorenylmethoxycarbonyl). The reagent for removing the amino protecting group is selected from TFA, H2O, LiOH, MeOH, EtOH and combinations thereof, preferably a combination of TFA and H2O, a combination of LiOH and MeOH, or a 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 bears 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 bears 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 bears a positive charge at a lower pH and does not bear 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 bears a positive charge at a high hydrogen ion concentration and does not bear 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 bears a charge or does not bear 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 bearing 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 bears 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 / cationized 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 comprising 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 has been removed from the amino group and / or a hydroxyl group has been removed from the carboxyl group and / or a hydrogen atom has been 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 acids in the present invention is not particularly limited without special indication, and can be either of natural origin, non-natural origin, or a mixture of both. The structural type of the amino acids in the present invention is not particularly limited without special indication, and can refer to L-type, D-type, or a mixture of both. In one embodiment of the present invention, the amino acid is a hydrophilic amino acid, glycine (Gly). The variant form in the present invention refers to a structural form that can be transformed into a target reactive group through any one of the chemical change processes such as oxidation, reduction, hydration, dehydration, electronic rearrangement, structural rearrangement, salt complexation and decomplexation, ionization, protonation, deprotonation, substitution, deprotection, changing the leaving group, etc. 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 decomplexation, 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 preparation method of the present invention to be smoothly implemented. 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 the number of structural units is not limited, and 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 heteroalicyclic linker, divalent heteroaromatic 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, diazahexane ring, 1-(2-pyridyl)hexahydro-1H-1,4-diazepine structure. 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 one of the following: small interfering RNA (siRNA), asymmetric interfering RNA (aiRNA), microRNA (miRNA), Dicer-substrate RNA (dsRNA), small 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 certain embodiments, inhibition of the expression of the target gene is achieved when the level of expression 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 level of expression of the target gene in the control sample or control mammal. In the present invention, methods for determining the level of expression 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 (such as 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 an adaptive immune response. Typically, an antigen can be or can contain 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. Normal 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, skimmed 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 preparations 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-adhesives, 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, cross-linked polyvinylpyrrolidone, 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 antigenic function. The antigen or antigenic 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 to combat 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 its structure is shown in the general formula (1-A): 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 -; 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-, -NH-, -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-; wherein, R c is independently H or C 1-12 alkyl each time it appears; p is an integer from 1 to 4; B1 and B2 are independently a linking bond or C 1-20 alkylene each time they appear; L1, L2, L3, and L4 are independently a linking bond or a divalent linking group -(CH2) tn L a (CH2) tn -; said La Selected from -OC(=O)-, -C(=O)O-, -OC(=O)O-, -CH(OH)-, -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-; wherein, s is 1, 2, 3 or 4; tn is independently an integer from 0 to 12 each time it appears; L1 and L3 are not simultaneously a linking bond; L2 and L4 are not simultaneously a linking bond; R1 and R2 are each independently a C 5-30 hydrocarbyl group or a C 5-30 hydrocarbyl derivative each time they appear; c is 2, 3 or 4. 1.1. In a specific embodiment of the present invention, a cationic lipid is characterized in that its structure is as shown in the general formula (1-A-1): wherein, tm is independently an integer from 1 to 5 each time it appears; Z is -O- or -NH-, and the definitions of the other symbols are the same as those in formula (1-A). 1.2. Core In the present invention, Core is a nitrogen-containing heterocyclic nucleus. In a specific embodiment of the present invention, the aforementioned Core is wherein, n is 1 or 2; preferably Core is Most preferably it is 1.3. 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)NH-, -(CH2) tm OC(=O)NH-, -(CH2) tm NHC(=O)NH-, -(CH2) tm O(CH2) tm-, -(CH2) tm C(=O)(CH2) tm -, -(CH2) tm C(=O)O(CH2) tm -, -C(=O)(CH2) tm C(=O)(CH2) tm -, -(CH2) tm C(=O)O(CH2) tm O-, -(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 OC(=O)NH(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 -, -(CH2) tm NHC(=O)NH(CH2) tm - and -(CH2) tm O(CH2) tm O- any one of them, and the left end is connected to the nitrogen-containing heterocycle; preferably -(CH2) tm O(CH2) tm -, -(CH2) tm C(=O)O(CH2) tm -, -(CH2) tm O-, -(CH2) tm C(=O)O(CH2) tm O-, -(CH2) tm NH-, -(CH2) tm C(=O)O(CH2) tm O(CH2) tm -, -(CH2)tm O(CH2) tm NH-, -(CH2) tm OC(=O)(CH2) tm - and -(CH2) tm O(CH2) tm Any one of O-; preferably, L is any one of -(CH2)C(=O)O(CH2)4-, -(CH2)C(=O)O(CH2)3-, -(CH2)C(=O)O(CH2)2O(CH2)2-, -(CH2)2O-, -(CH2)2NH-, -(CH2)2O(CH2)2NH-, -(CH2)C(=O)O(CH2)2O- and -(CH2)2O(CH2)2O-, and the left end is connected to the nitrogen-containing heterocycle. 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, B1 and B2 are any one of the following situations: Situation (1): B1 and B2 are each independently C 1-20 alkylene, more preferably C 2-10 alkylene; Situation (2): One of B1 and B2 is a linking bond and the other is C 1-20 alkylene; Situation (3): B1 and B2 are both linking bonds; More preferably, B1 and B2 are selected from the aforementioned situation (1) or situation (3); Among them, the aforementioned C 2-10 alkylene is preferably any one of ethylene, propylene, butylene, pentylene, hexylene, heptylene, octylene. 1.5.L1, L2 In the present invention, each occurrence of L1 and L2 is independently a linking bond or L a , and the L a is selected from -OC(=O)-, -C(=O)O-, -OC(=O)O-, -CH(OH)-, -C(=O)-, -O-, -NH-, -O(CH2) sAny one of 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-. In a specific embodiment of the present invention, preferably, 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; More preferably, L1 and L2 are each independently a linking bond, -C(=O)-, -O-, -NH-, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -CH(OH)-, -OC(=O)NH-, -NHC(=O)O-, -NHC(=O)- and -C(=O)NH-. 1.6. L3, L4 In the present invention, each occurrence of L3 and L4 is independently a linking bond, -L a -, -(CH2) tn L a -, -L a (CH2) tn -, -(CH2) tn L a (CH2) tn -, where tn is an integer from 1 to 12. In a specific embodiment of the present invention, preferably, L3 and L4 are each independently -(CH2) tn C(=O)-, -(CH2) tn C(=O)O-, -(CH2) tn OC(=O)-, -(CH2) tn OC(=O)O-, -(CH2) tn OC(=O)NH-, -(CH2) tnAny one of NHC(=O)O-, the right end of which is connected to B1 or B2; preferably, each of L3 and L4 is independently any one of a linking bond, -CH2CH(OH)-, -(CH2)2C(=O)NH-, -C(=O)- and -C(=O)O-; more preferably, L3 and L4 are the same and are a linking bond, -CH2CH(OH)- or -(CH2)2C(=O)NH-. 1.7.R1, R2 In the present invention, each of R1 and R2 is independently C 5-30 a straight-chain hydrocarbon group, C 5-30 a branched-chain hydrocarbon group or C 5-30 a hydrocarbon group derivative, and the C 5-30 hydrocarbon group derivative is represented as The straight-chain hydrocarbon group and the branched-chain hydrocarbon group are each independently substituted or unsubstituted, and the substitution is preferably by C 1-6 an alkyl group, a halogen or a hydroxyl group; the hydrocarbon group is preferably an alkyl group, an alkenyl group or an alkynyl group. In a specific embodiment of the present invention, 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. In a specific embodiment of the present invention, the branched-chain hydrocarbon group is a branched-chain alkyl group, a branched-chain alkenyl group or a branched-chain alkynyl group, and each is independently 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 C 1-15 an alkyl group, C 2-15 an alkenyl group and C 2-15 an 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 a C 5-30 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 a C 5-30 branched hydrocarbon group Case (4): R1 and R2 are each independently Case (5): One of R1 and R2 is a C 5-30 linear hydrocarbon group or a 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 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 - L3 - B1 - L1 - R1 and - L4 - 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, the structure of the cationic lipid of the present invention is selected from any one of the following general formulas: wherein, L1, L2, L3, L4, B1, and B2 are not linker bonds; the definitions of other symbols are the same as those in formula (1 - A). In a specific embodiment of the present invention, the structure of the aforementioned cationic lipid preferably satisfies any one of the following general formulas: More preferably, the structure of the cationic lipid satisfies any one of the following general formulas: Most preferably, the structure of the cationic lipid satisfies any one of the following general formulas: In all of the foregoing general formulas, it is preferred that each occurrence of L1 and L2 is 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 independently any one of -C(=O)-, -C(=O)O-, -OC(=O)-, -OC(=O)O-. More preferably, the structure of the cationic lipid satisfies any one of formulas (4-1) to (4-3); preferably, in formula (4-1), L3 and L4 are each independently -CH2CH(OH)-, and L1 and L2 are any one of -C(=O)O-, -OC(=O)-, -OC(=O)O-; in formula (4-3), R1 and R2 are each independently C 5-25 alkenyl or C 5-25 alkynyl. 1.10. Specific structural examples In one embodiment of the present invention, it is preferred that the structure of the 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', and CORE-AA'. The preparation process of the present invention may involve a raw material CORE0 containing a nitrogen-containing heterocyclic nucleus, where CORE0 contains c identical functional groups F0, and F0 is a group capable of reacting with the end group of an amino acid or an amino acid derivative, preferably a protected or unprotected -OH, -COOH, -NH2, -NH-, and c is 2, 3 or 4. CORE0 can be obtained by purchase or by further modifying 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 12, S12-1 and S12-2 CORE0 can be obtained by a substitution reaction followed by removal of the Boc protecting group In the present invention, CORE0 is selected from any one of the following structures: The preparation process of the present invention may involve a small molecule intermediate IM-N containing a reactive group and a hydrophobic hydrocarbon tail chain, and the structure is represented as F C -B1-L1-R1, F N -B2-L2-R2, where F C and F N are groups capable of reacting with the end group of an amino acid or an amino acid derivative, preferably -OH, -COOH, -Br, -CHO, -CH=CH-, and the definitions of the remaining symbols are the same as those described in the general formula (1-A). IM-N can be prepared by any suitable chemical reaction, and the any suitable chemical reaction includes single-step or stepwise reactions such as simple esterification, amidation, alkylation, addition or substitution. For example, in Example 1, S1-4 and S1-5 The small molecule intermediate IM-N is obtained by a condensation reaction In the present invention, the structure of the aforementioned IM-N is preferably F C -R1, F N -R2, F C -L1-R1, F N -L2-R2, F C -B1-L1-R1, F N -B2-L2-R2, and specifically, more preferably, IM-N is selected from any one of the following structures: The preparation process of the present invention may involve an intermediate IM-AA', which contains a reactive amino acid end group and at least two hydrophobic hydrocarbon tails, and its structure is represented as wherein, AA' contains a reactive amino acid end group, and the definitions of other symbols are the same as those described in the general formula (1-A). IM-AA' can be obtained by performing one-step or multi-step identical or different modifications of IM-N on an amino acid or its derivative. In the present invention, the structure of the aforementioned IM-AA' is preferably any one of them. Specifically, IM-AA' is more preferably selected from any one of the following structures: The preparation process of the present invention may involve an intermediate IM-AA, which contains an amino acid residue and at least two hydrophobic hydrocarbon chains, and its 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 other symbols are the same as those described in the general formula (1-A). IM-AA can be obtained by functionalizing the reactive amino acid end group of IM-AA'. In the present invention, the structure of the aforementioned IM-AA is preferably any one of them. Specifically, IM-AA is more preferably 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 its structure is represented as wherein, AA' contains a reactive amino acid end group, and the definitions of each symbol are the same as those described in the general formula (1-A). CORE-AA' can be obtained by performing one-step or stepwise identical or different reactions of CORE0 with an amino acid or its derivative. For example, in Example 1, S1-1 and S1-2 can obtain the small molecule intermediate CORE-AA' through a condensation reaction and then removing the Boc protecting group In the present invention, 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; or it can also be obtained by reacting any one of the aforementioned CORE-AA’ with any one of IM-N. 2.2. Description of relevant raw materials and / or steps during the preparation process 2.2.1. Condensing agents, oxidizing agents, reducing agents 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, vanadium oxytrifluoride, chromium(III) oxide, manganese(III) acetate, TEMPO, ammonium cerium(IV) nitrate, bromine, N-oxidopyridine, silver oxide, O-ethyl peroxycarbonate, manganese(III) acetylacetonate, vanadium(IV) 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 from ammonia and aldehyde or ketone to an amino group; preferably, it is one or a combination of sodium borohydride, sodium cyanoborohydride, lithium aluminum hydride, borane, diborane, diisobutylaluminum hydride, diisopinocampheylborane, lithium borohydride, zinc borohydride, borane-pyridine, borane-methyl sulfide, borane-tetrahydrofuran, etc.; more preferably, it is sodium cyanoborohydride. In the present invention, the solvent for the reaction can be a solvent-free or aprotic solvent. The aprotic solvents include toluene, benzene, xylene, acetonitrile, ethyl acetate, ether, methyl tert-butyl ether, tetrahydrofuran, chloroform, dichloromethane, dimethyl sulfoxide, dimethylformamide or dimethylacetamide. Preferably, they 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, they are triethylamine and pyridine. 2.2.2. "Protection" and "deprotection" of relevant groups involved in the reaction process In the present invention, there are "protection" and "deprotection" processes of relevant groups involved in the reaction process. To prevent the functional group from affecting the reaction, the functional group is usually protected. And when there are two or more functional groups, only the target functional group is selectively reacted, so other functional groups are protected. The protecting group not only stably protects the functional group as the object, but also needs to be easily removed as required. 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 hydrogenating reducing agent and a hydrogen donor. The water content in this reaction system should be less than 1% for the reaction to proceed smoothly. There is no restriction on the hydrogenation reduction catalyst, and palladium and nickel are preferred. However, the carrier is not restricted, but alumina or carbon is preferred, and carbon is more preferred. The amount of palladium used is 1 to 100 wt% of the hydroxy compound to be protected, preferably 1 to 20 wt% of the hydroxy compound to be protected. There is no particular restriction on the reaction solvent, 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. There is no particular restriction on the hydrogen donor, but hydrogen, cyclohexene, 2-propanol, ammonium formate, etc. are preferred. The reaction temperature is preferably 25 to 40 °C. There is no particular restriction on the reaction time, and the reaction time is negatively correlated with the amount of the catalyst used. It is preferably 1 to 5 hours. B: Deprotection of silyl ether protecting groups Compounds used for such hydroxy 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 ion-containing compounds, preferably tetrabutylammonium fluoride, tetraethylammonium fluoride, hydrofluoric acid, potassium fluoride, and tetrabutylammonium fluoride and potassium fluoride are more preferred. The amount of the fluorine-containing reagent used is 5 to 20 times the molar equivalent of the hydroxy group to be protected, preferably 8 to 15 times the initiator. If the amount of fluorine used is less than 5 times the molar equivalent of the hydroxy group to be protected, incomplete deprotection will occur; when the amount of the deprotection reagent used is greater than 20 times the molar equivalent of the hydroxy group to be protected, the excess reagent or compound will cause trouble in purification and may be mixed into subsequent steps, thus causing side reactions. There is no particular restriction on the reaction solvent, as long as it can dissolve the reactants and products. Aprotic solvents are preferred, and tetrahydrofuran and dichloromethane are more preferred. 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 groups The deprotection of the tert-butyl group is carried out under acidic conditions, and the solution pH is preferably 0 to 4. The acid is not particularly restricted, but acetic acid, phosphoric acid, sulfuric acid, hydrochloric acid, and nitric acid are preferred, and hydrochloric acid is more preferred. There is no particular restriction on the reaction solvent, as long as it can dissolve the reactants and products. Water is preferred. 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 a hydroxy group, a mercapto group, or an amino group, corresponding to the formation of an ether bond, a thioether bond, a secondary amino group, or a tertiary amino group in turn. Examples are as follows: 2.2.3.1. Alkylation of substrate alcohols with sulfonates and halides In the presence of a base, an ether intermediate is obtained by nucleophilic substitution of a substrate alcohol 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 alcohol, 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 alcohol, 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 alcohol, 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 ether intermediate and excess sulfonate and halide, which can be purified by anion exchange resin, osmosis, ultrafiltration, etc. Among them, there is no particular limitation on the anion exchange resin, as long as the target product can undergo ion exchange and adsorption on the resin. Ion exchange resins of tertiary amines or quaternary ammonium salts with skeletons such as dextran, agarose, polyacrylate, polystyrene, and polydiphenylethylene are preferred. There is no limitation on the solvent for osmosis and ultrafiltration. Generally, water or an organic solvent can be used. There is no particular limitation on the organic solvent as long as the product can be dissolved in it. Dichloromethane, chloroform, etc. are preferred. The reaction solvent is not limited, and an aprotic solvent is preferred, such as toluene, benzene, xylene, acetonitrile, ethyl acetate, tetrahydrofuran, chloroform, dichloromethane, dimethyl sulfoxide, dimethylformamide, or dimethylacetamide. Dimethylformamide, dichloromethane, dimethyl sulfoxide, or tetrahydrofuran are more preferred. The base includes an organic base (such as triethylamine, pyridine, 4-dimethylaminopyridine, imidazole, or diisopropylethylamine) or an inorganic base (such as sodium carbonate, sodium hydroxide, sodium bicarbonate, sodium acetate, potassium carbonate, or potassium hydroxide). An organic base is 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 a sulfonate and a halide A. Alkylation of the substrate amine with a sulfonate and a halide In the presence of a base, an amine intermediate is obtained by nucleophilic substitution of a 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 resulting product is a mixture of amine intermediates and excess sulfonate esters or halides, which can be purified by methods such as column chromatography, anion exchange resin, dialysis, ultrafiltration, etc. Among them, there is no particular limitation on the anion exchange resin, as long as the target product can undergo ion exchange and adsorption on the resin. Ion exchange resins of tertiary amines or quaternary ammonium salts with skeletons such as dextran, agarose, polyacrylate, polystyrene, and polydiphenylethylene are preferred. There is no limitation on the solvents for dialysis and ultrafiltration. Generally, water or organic solvents can be used. There is no particular limitation on the organic solvents as long as the product can dissolve in them. 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. 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 ester or halide, preferably 1 to 10 times, and more preferably 3 to 5 times. 2.2.3.3. Alkylation reaction of substrate amine with aldehyde derivatives After an imine intermediate is obtained by reacting the 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, and 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, increasing the purification difficulty. Among them, the reaction product can be purified by means such as cation exchange resin, dialysis, ultrafiltration, etc. There is no particular limitation on the said cation exchange resin, as long as it can achieve separation by exchanging with quaternary ammonium cations. There is no limitation on the solvents for dialysis and ultrafiltration. Generally, water or organic solvents can be used. There is no particular limitation on the organic solvents as long as the product can dissolve in them. Dichloromethane, chloroform, etc. are preferred. The reaction solvent is not limited, 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.; water and methanol are more preferred. The reducing agent is not particularly limited as long as it can reduce imine to amine. Sodium borohydride, lithium aluminum hydride, sodium cyanoborohydride, Zn / AcOH, etc. are preferred, and sodium cyanoborohydride is more preferred. Generally, the amount of the reducing agent used is 0.5 to 50 times the amount of the aldehyde derivative substance, and more preferably 1 to 10 times. 3.1. Lipid composition In the present invention, a lipid composition contains any one of the cationic lipids having the structure shown by the general formula (1-A) as described above. In a specific embodiment of the present invention, preferably, the lipid composition, in addition to containing the cationic lipid having the structure shown by the general formula (1-A), further contains one or more of phospholipids, steroid lipids, and polyethylene glycolated lipids, selected from any one of the following situations: Situation (1): Further contains phospholipids; Situation (2): Further contains steroid lipids; Situation (3): Further contains polyethylene glycolated lipids; Situation (4): Further contains phospholipids and steroid lipids; Situation (5): Further contains phospholipids and polyethylene glycolated lipids; Situation (6): Further contains steroid lipids and polyethylene glycolated lipids; Situation (7): Further contains phospholipids, steroid lipids, and polyethylene glycolated lipids; Situation (8): Further contains phospholipids, steroid lipids, polyethylene glycolated lipids, and another cationic lipid; Situation (9): Further contains phospholipids, steroid lipids, polyethylene glycolated lipids, and anionic lipids; More preferably, it also contains three lipids, namely neutral lipids, steroid lipids, and polyethylene glycolated lipids, at the same time. In a specific embodiment of the present invention, the phospholipid in the lipid composition is preferably any one of 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-stearoylethanolamine (SOPE), 1-stearoyl-2-oleoyl-phosphatidylcholine (SOPC), sphingomyelin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidic acid, palmitoyl oleoyl phosphatidylcholine, lysophosphatidylcholine and lysophosphatidylethanolamine (LPE) and their combinations. 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, tomatine, ursolic acid, α-tocopherol and their combinations. In a specific embodiment of the present invention, the polyethylene glycolated lipid in the lipid composition is preferably 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 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 (PEG-DMG) and its composition. In a specific embodiment of the present invention, the polyethylene glycolated lipid in the lipid composition is preferably any one of the following structures and its composition: Wherein, n1 is an integer from 25 to 300, and more preferably n1 is any one of 44, 45, 46, 47, 48. 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)propan-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 (nonadec-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 lipid composition contains 20-80% of the cationic lipid represented by formula (1-A), 5-16% of phospholipids, 25-55% of steroid lipids, and 0.5-10% of polyethylene glycolated lipids, and the percentages are the molar percentages of each lipid in the total lipids in the solution containing the solvent. 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, any of the aforementioned lipid compositions is preferably used, and the molar percentage of the cationic lipid in the total lipids 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, in any of the aforementioned lipid compositions, the molar percentage of the phospholipid in the total lipids 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, in any of the aforementioned lipid compositions, the molar percentage of the steroid lipid in the total lipids 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, in any of the aforementioned lipid compositions, the molar percentage of the polyethylene glycolated lipid in the total lipids 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, and preferably the ethanol injection method and the microfluidic method. 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 aforementioned lipid compositions and a drug, wherein the lipid composition contains any of the aforementioned cationic lipids having a structure as shown in the general formula (1-A), 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 drugs are 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 drugs are 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: anti-tumor agent, antiviral agent, anti-fungal 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 agents, hormones, hormone antagonists, immunomodulators, neurotransmitter antagonists, antiglaucoma drugs, vitamins, sedatives, and imaging agents, taxol, cytochalasin B, gramicidin D, ethidium bromide, emetine, mitomycin, etoposide, teniposide, colchicine, daunorubicin, mitoxantrone, mithramycin, 1-dehydrotestosterone, glucocorticoids, procaine, tetracaine, lidocaine, puromycin, maytansinoids. In a specific embodiment of the present invention, it is preferred that the N / P ratio of the lipid composition to the nucleic acid is (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 solution, or physiological saline, more preferably phosphate buffer solution or physiological saline, and most preferably physiological saline; it is preferred that 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, and 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 to 12 h, preferably 0.2 to 6 h, more preferably 0.5 to 3 h; preferably, the complexation time is 0.1 to 12 h, preferably 0.2 to 5 h, more preferably 0.5 to 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 lipid drug compositions described above. In a specific embodiment of the present invention, preferably, the aforementioned lipid nanoparticles are LNP-drug compositions, LPP-drug compositions or PNP-drug compositions; preferably LNP-drug compositions; more preferably LNP-nucleic acid drug compositions; more preferably LNP-mRNA drug compositions. 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 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, 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 glycolated lipid, fully dissolve them 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 dissolved with cryoprotectant, and perform water bath ultrasonic treatment to form a semi-transparent emulsion; (3) Add the emulsion into a high-pressure homogenizer for overpressure, and then add the overpressurized emulsion into 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 preparation method of liposomes in the present invention, 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, the 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 or sodium acetate buffer; (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 the organic solvent 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, antisolvent precipitation, membrane 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 1H 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 (default is 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 (default is the number-average degree of polymerization) of the polymer is calculated according to its molecular weight. The preparation methods of cationic lipids, lipid compositions, lipid drug compositions, lipid drug composition preparations and the bioactivity tests of lipid drug compositions are further described below in combination 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: Boc-glycine (S1-2, 1.47 g, 8.4 mmol), p-toluenesulfonic acid (TsOH, 0.76 g, 4.4 mmol) and anhydrous toluene (20 mL) were successively added to a round-bottom 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 1,4-bis(2-hydroxyethyl)piperazine (S1-1, 0.70 g, 4.0 mmol) was added in batches. Then the temperature was raised to 135 °C and refluxed overnight. After the reaction ended, the reaction solution was concentrated. The residue was dissolved in dichloromethane and washed twice with water, twice with saturated sodium bicarbonate aqueous solution, and once with saturated brine. Finally, it was dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. The crude product was purified by column chromatography to obtain the amino-Boc protected ester (1.00 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. The dichloromethane solution of the above ester (0.97 g, 2.5 mmol) was slowly added dropwise under ice bath conditions, and the reaction was carried out at room temperature for 2 h. After the reaction ended, water was added to the reaction solution and stirred evenly, and then extracted. The organic phase was dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. Recrystallization was carried out to obtain S1-3 with two naked amino groups (0.67 g). Step b: Under nitrogen protection, dicyclohexylcarbodiimide (DCC, 3.63 g, 17.6 mmol) was added to a round-bottom flask containing 8-bromooctanoic acid (S1-4, 1.78 g, 8.0 mmol), 4-nonyne-1-ol (S1-5, 1.34 g, 9.6 mmol) and 4-(dimethylamino)pyridine (DMAP, 0.24 g, 2.0 mmol) dissolved in dichloromethane (50 mL). The reaction was carried out at room temperature for 16 h. After the reaction ended, the precipitate was removed by filtration, and the filtrate was concentrated. The crude product was purified by column chromatography to obtain 4-nonyne-1-yl 8-bromooctanoate (S1-6, 2.25 g). Step c: Under nitrogen protection, compound S1-3 (0.29 g, 1.0 mmol) was dissolved in acetonitrile (30 mL). S1-6 (2.07 g, 6.0 mmol) and N,N-diisopropylethylamine (DIPEA, 0.65 g, 5.0 mmol) were successively added with slow stirring, and the reaction was stirred at room temperature for about 20 h. After the reaction ended, the reaction solution was concentrated, then dissolved in dichloromethane, and extracted successively with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution. The organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. The crude product was purified by column chromatography to obtain the cationic lipid E1-1 (1.09 g). 1HNMR (400 MHz, CDCl3) δ: 4.25 (s, 4H, pip-CH2CH2-), 4.18 - 4.11 (m, 8H, -C(=O)OCH2-), 3.35 (s, 4H, -OC(=O)CH2N<), 2.84 - 2.42 (m, 20H; 8H, pip-H; 4H, pip-CH2CH2-; 8H, >NCH2CH2-), 2.33 - 2.20 (m, 16H, -CH2C≡CCH2(CH2)2CH3), 2.18 - 2.11 (m, 8H, -CH2CH2C(=O)O-), 1.84 - 1.76 (m, 8H, -C(=O)OCH2CH2CH2-), 1.64 - 1.23 (m, 56H, -CH2CH2CH2-, -CH2CH3), 0.89 (t, 12H, -CH2CH3). MS (ESI): m / z = 1345.6 ([M+H] + )。 Example 2: Cationic Lipid E2-1 The preparation process is as follows: Under ice bath conditions, dissolve S1-3 (0.58 g, 2.0 mmol) in dichloromethane solution (30 mL). With vigorous stirring, add (9Z,12Z)-octadeca-9,12-dienal (S2-1, 1.58 g, 6.0 mmol), and then add sodium triacetoxyborohydride (NaBH(OAc)3, 1.27 g, 6.0 mmol) in three portions within 10 minutes. Warm the reaction system to room temperature and continue the reaction for 2 h. After the reaction is completed, add NaOH aqueous solution (1 M, 10 mL). Stir the reaction solution for 15 minutes and then dilute it with water. Extract the reaction solution twice with dichloromethane (15 mL * 2), combine the organic phases, wash with brine (15 mL), dry over anhydrous magnesium sulfate, filter, concentrate, and purify the crude product by column chromatography to obtain cationic lipid E2-1 (2.38 g, 92.9%). 11H NMR (400 MHz, CDCl3) δ: 5.45 - 5.24 (m, 16H, -CH=CH-), 4.24 (t, 4H, pip-CH2CH2-), 3.32 (s, 4H, -OC(=O)CH2N<), 2.82 - 2.43 (m, 28H; 8H, pip-H; 4H, pip-CH2CH2-; 8H, >NCH2CH2-; 8H, -CH=CHCH2CH=CH-), 2.03 - 1.97 (m, 16H, -CH=CHCH2-), 1.64 - 1.22 (m, 72H, -CH2CH2CH2-, -CH2CH3), 0.89 (t, 12H, -CH2CH3). MS (ESI): m / z = 1281.2 ([M+H] + )。 Example 3: Cationic Lipid E3-1 The preparation process is as follows: Step a: (9Z,12Z)-9,12-Octadecadien-1-ol (S3-1, 2.39 g, 9.0 mmol) and triethylamine (2.59 g, 26.7 mmol) were successively added to a dichloromethane solution (50 mL) at 0 °C. Subsequently, a dichloromethane (10 mL) solution containing acryloyl chloride (S3-2, 1.23 g, 13.5 mmol) was added dropwise to the reaction system, and the reaction solution was stirred at 20 °C for 2 h. After the reaction, the solid precipitated in the reaction solution was filtered, the filtrate was collected, washed successively with water and 5% hydrochloric acid by mass fraction, the organic phase was dried over anhydrous magnesium sulfate, filtered, concentrated, and the crude product was purified by column chromatography to obtain the compound (9Z,12Z)-9,12-dienyloctadecane acrylate (S3-3, 2.17 g). Step b: S1-3 (0.27 g, 1.0 mmol) was dissolved in isopropanol, an adequate amount of anhydrous potassium carbonate was added with stirring, and the mixture was stirred at room temperature until the reaction solution became alkaline. Then S3-3 (1.93 g, 6.0 mmol) was added to the reaction solution, and the reaction solution was placed in a reflux device (90 °C) and stirred for another 36 h. After the reaction, the reaction solution was concentrated, and the crude product was purified by column chromatography to obtain the cationic lipid E3-1 (1.20 g). 11H NMR (400 MHz, CDCl3) δ: 5.44 - 5.25 (m, 16H, -CH=CH-), 4.24 (t, 4H, pip-CH2CH2-), 4.17 - 4.08 (m, 8H, -C(=O)OCH2-), 3.35 (s, 4H, -OC(=O)CH2N<), 2.84 - 2.43 (m, 28H; 8H, pip-H; 4H, pip-CH2CH2-; 8H, >NCH2CH2-; 8H, -CH=CHCH2CH=CH-), 2.17 - 2.10 (m, 8H, -CH2CH2C(=O)O-), 2.03 - 1.97 (m, 16H, -CH=CHCH2-), 1.84 - 1.76 (m, 8H, -C(=O)OCH2CH2CH2-), 1.65 - 1.22 (m, 64H, -CH2CH2CH2-, -CH2CH3), 0.89 (t, 12H, -CH2CH3). MS (ESI): m / z=1569.3 ([M + H] + )。 Example 4: Cationic Lipid (E4-1) The preparation process is as follows: Dissolve S1-3 (0.35 g, 1.2 mmol) in isopropanol, add sufficient anhydrous potassium carbonate under stirring, and stir at room temperature until the reaction solution becomes alkaline. Then add N-dodecylacrylamide (S4-1, 1.72 g, 7.2 mmol) to the reaction solution, and place the reaction solution in a reflux device (90 °C) and continue stirring for 36 h. After the reaction is completed, concentrate the reaction solution, and the crude product is purified by column chromatography to obtain cationic lipid E4-1 (1.13 g). 1 1H NMR (400 MHz, CDCl3) δ: 4.24 (t, 4H, pip-CH2CH2-), 3.28 (dd, 8H, -C(=O)NHCH2-), 3.24 (s, 4H, -OC(=O)CH2N<), 2.81 - 2.62 (m, 20H; 8H, pip-H; 4H, pip-CH2CH2-; 8H, >NCH2CH2-), 2.39 (t, 8H, -CH2C(=O)NH-), 1.64 - 1.22 (m, 80H, -CH2CH2CH2-, -CH2CH3), 0.87 (t, 12H, -CH2CH3). MS (ESI): m / z=1245.1 ([M + H] + )。 Example 5: Cationic Lipid (E5-1) The preparation process is as follows: Step a: Under nitrogen protection, DCC (3.63 g, 17.6 mmol) was added to a round-bottom flask containing 4-hydroxybutyl acrylamide (S5-1, 1.14 g, 8.0 mmol), nonanoic acid (S5-2, 1.52 g, 9.6 mmol), and DMAP (0.24 g, 2.0 mmol) dissolved in dichloromethane (50 mL). 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 S5-3 (1.86 g). Step b: S1-3 (0.29 g, 1.0 mmol) was dissolved in isopropanol. Anhydrous potassium carbonate in sufficient amount was added with stirring, and the mixture was stirred at room temperature until the reaction solution became alkaline. Then S5-3 (1.70 g, 6.0 mmol) was added to the reaction solution, and the reaction solution was placed in a reflux apparatus (90 °C) and stirred for 36 h. After the reaction was completed, the reaction solution was concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E5-1 (1.08 g). 1 H NMR (400 MHz, CDCl3) δ: 4.24 (t, 4H, pip-CH2CH2-), 4.16 - 4.14 (t, 8H, -C(=O)OCH2-), 3.28 (dd, 8H, -C(=O)NHCH2-), 3.25 (s, 4H, -OC(=O)CH2N<), 2.82 - 2.62 (m, 20H; 8H, pip-H; 4H, pip-CH2CH2-; 8H, >NCH2CH2-), 2.39 (t, 8H, -CH2C(=O)NH-), 2.18 - 2.11 (m, 8H, -CH2CH2C(=O)O-), 1.85 - 1.76 (m, 8H, -C(=O)OCH2CH2CH2-), 1.64 - 1.23 (m, 56H, -CH2CH2CH2-, -CH2CH3), 0.88 (t, 12H, -CH2CH3). MS (ESI): m / z=1421.0 ([M+H] + )。 Example 6: Cationic lipid (E6-1) The preparation process is as follows:[[]]END]] S1-3 (0.35 g, 1.2 mmol) was dissolved in isopropanol. Anhydrous potassium carbonate in sufficient amount was added with stirring, and the mixture was stirred at room temperature until the reaction solution became alkaline. Then dodecyl acrylate (S6-1, 1.73 g, 7.2 mmol) was added to the reaction solution, and the reaction solution was placed in a reflux apparatus (90 °C) and stirred for 36 h. After the reaction was completed, the reaction solution was concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E6-1 (1.13 g). 11H NMR (400 MHz, CDCl3) δ: 4.24 (t, 4H, pip-CH2CH2-), 4.16 - 4.09 (m, 8H, -C(=O)OCH2-), 3.36 (s, 4H, -OC(=O)CH2N<), 2.85 - 2.43 (m, 20H; 8H, pip-H; 4H, pip-CH2CH2-; 8H, >NCH2CH2-), 2.18 - 2.11 (m, 8H, -CH2CH2C(=O)O-), 1.83 - 1.76 (m, 8H, -C(=O)OCH2CH2CH2-), 1.64 - 1.22 (m, 72H, -CH2CH2CH2-, -CH2CH3), 0.89 (t, 12H, -CH2CH3). MS (ESI): m / z = 1249.0 ([M+H] + )。 Example 7.1: Cationic Lipid (E7-1) The preparation process is as follows: S1-3 (0.35 g, 1.2 mmol) and DIPEA (0.46 g, 3.6 mmol) were successively added to a methanol solution of 1,2-epoxydodecane (S7-1, 1.32 g, 7.2 mmol), and the reaction solution was placed in a reflux device (90 °C) and stirred for 24 h. After the reaction, the reaction solution was concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E7-1 (0.83 g). 1 1H NMR (400 MHz, CDCl3) δ: 4.23 (t, 4H, pip-CH2CH2-), 3.51 - 3.41 (m, 4H, -CH(OH)-), 3.32 (s, 4H, -OC(=O)CH2N<), 2.78 - 2.31 (m, 20H; 4H, pip-CH2CH2-; 8H, pip-H; 8H, >CHCH2N<), 1.44 - 1.23 (m, 72H, -CH2CH2CH2-, -CH2CH3), 0.88 (t, 12H, -CH2CH3). MS (ESI): m / z = 1024.9 ([M+H] + )。 Example 7.2: Cationic Lipid (E7-2) The raw material S7-1 in Example 7.1 was replaced with raw material 1,2-epoxytetradecane (S7-2, 1.53 g, 7.2 mmol), and the preparation was carried out according to the same reaction steps to obtain cationic lipid E7-2 (0.93 g). 11H NMR (400 MHz, CDCl3) δ: 4.22 (t, 4H, pip-CH2CH2-), 3.52 - 3.41 (m, 4H, -CH(OH)-), 3.33 (s, 4H, -OC(=O)CH2N<), 2.78 - 2.30 (m, 20H; 4H, pip-CH2CH2-; 8H, pip-H; 8H, >CHCH2N<), 1.45 - 1.22 (m, 88H, -CH2CH2CH2-, -CH2CH3), 0.88 (t, 12H, -CH2CH3). MS (ESI): m / z = 1137.0 ([M+H] + )。 Example 7.3: Cationic Lipid (E7-3) Replace the raw material S7-1 in Example 7.1 with the raw material 1,2-epoxyhexadecane (S7-3, 1.73 g, 7.2 mmol), and prepare according to the same reaction steps to obtain the cationic lipid E7-3 (1.02 g). 1 1H NMR (400 MHz, CDCl3) δ: 4.24 (t, 4H, pip-CH2CH2-), 3.51 - 3.42 (m, 4H, -CH(OH)-), 3.35 (s, 4H, -OC(=O)CH2N<), 2.78 - 2.31 (m, 20H; 4H, pip-CH2CH2-; 8H, pip-H; 8H, >CHCH2N<), 1.42 - 1.22 (m, 104H, -CH2CH2CH2-, -CH2CH3), 0.87 (t, 12H, -CH2CH3). MS (ESI): m / z = 1249.2 ([M+H] + )。 Example 8: Cationic Lipid (E8-1) The preparation process is as follows: Step a: Under nitrogen protection, add DCC (3.63 g, 17.6 mmol) to a round-bottom flask containing undecanol (S8-2, 1.65 g, 9.6 mmol), 8-bromooctanoic acid (S8-1, 1.56 g, 8.0 mmol), and DMAP (0.24 g, 2.0 mmol) dissolved in dichloromethane (30 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 undecyl 6-bromohexanoate (S8-3, 2.30 g). Step b: Under nitrogen protection, dissolve compound S1-3 (0.29 g, 1.0 mmol) in acetonitrile (30 mL). Sequentially add S8-3 (2.09 g, 6.0 mmol) and DIPEA (0.65 g, 5.0 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 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 cationic lipid E8-1 (1.11 g). 1 H NMR (400 MHz, CDCl3) δ: 4.24 (t, 4H, pip-CH2CH2-), 4.16 - 4.09 (m, 8H, -C(=O)OCH2-), 3.36 (s, 4H, -OC(=O)CH2N<), 2.84 - 2.43 (m, 20H; 8H, pip-H; 4H, pip-CH2CH2-; 8H, >NCH2CH2-), 2.18 - 2.10 (m, 8H, -CH2CH2C(=O)O-), 1.84 - 1.76 (m, 8H, -C(=O)OCH2CH2CH2-), 1.64 - 1.22 (m, 88H, -CH2CH2CH2-, -CH2CH3), 0.89 (t, 12H, -CH2CH3). MS (ESI): m / z = 1361.1 ([M+H] + )。 Example 9: Cationic Lipid (E9-1) The preparation process is as follows: Step a: Add 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 2.87 g, 15.0 mmol) and 1-hydroxybenzotriazole (HOBt, 2.03 g, 15.0 mmol) successively to a round-bottom flask containing S1-2 (2.63 g, 15.0 mmol) and DIPEA (1.94 g, 15.0 mmol) dissolved in dichloromethane. React at room temperature for 10 minutes, then add 1,4-piperazinediethylamine (S9-1, 0.88 g, 5.0 mmol) in batches, and stir the reaction solution at room temperature for 12 h. After the reaction is completed, add saturated NaHCO3 (10 mL) to quench the reaction. Extract the aqueous phase with dichloromethane three times (20 mL * 3). Dry the organic phase with anhydrous magnesium sulfate, filter, concentrate the filtrate, and purify the crude product by column chromatography to obtain S9-2 (1.41 g). Step b: Removal of the Boc protecting group. In a dry and clean round-bottom flask, a solution of trifluoroacetic acid / dichloromethane (1:2, v / v) was prepared. The dichloromethane solution of S9-2 (0.97 g, 2.0 mmol) was slowly added dropwise under an ice bath, 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, followed by extraction. The organic phase was dried over anhydrous magnesium sulfate, filtered, the filtrate was concentrated, and recrystallization was performed to obtain S9-3 with an exposed amino group (0.53 g, 92.5%). Step c: Dissolve S9-3 (0.29 g, 1.0 mmol) in isopropanol, add a sufficient amount of anhydrous potassium carbonate under stirring, and stir at room temperature until the reaction solution becomes alkaline. Then add S6-1 (1.44 g, 6.0 mmol) to the reaction solution, and place the reaction solution in a reflux device (90 °C) and continue to stir and react for 36 h. After the reaction was completed, the reaction solution was concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E9-1 (0.95 g). 1 H NMR (400 MHz, CDCl3) δ: 4.15 - 4.08 (m, 8H, -C(=O)OCH2-), 3.46 - 3.33 (m, 4H, pip-CH2CH2-), 3.03 (s, 4H, -NHC(=O)CH2-), 2.84 - 2.43 (m, 20H; 8H, pip-H; 4H, pip-CH2CH2-; 8H, >NCH2CH2-), 2.18 - 2.10 (m, 8H, -CH2CH2C(=O)O-), 1.84 - 1.76 (m, 8H, -C(=O)OCH2CH2-), 1.62 - 1.22 (m, 72H, -CH2CH2CH2-, -CH2CH3), 0.88 (t, 12H, -CH2CH3). MS (ESI): m / z=1247.1 ([M+H] + )。 Example 10: Cationic lipid (E10-1) The preparation process is as follows: S9-3 (0.34 g, 1.2 mmol) and DIPEA (0.46 g, 3.6 mmol) were successively added to the methanol solution of S7-1 (1.32 g, 7.2 mmol), and the reaction solution was placed in a reflux device (90 °C) and continued to stir and react for 24 h. After the reaction was completed, the reaction solution was concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E10-1 (0.82 g). 11H NMR (400 MHz, CDCl3) δ: 3.51 - 3.33 (m, 8H; 4H, -CH(OH)-; 4H, pip-CH2CH2-), 3.04 (s, 4H, -NHC(=O)CH2-), 2.78 - 2.31 (m, 20H; 4H, pip-CH2CH2-; 8H, pip-H; 8H, >CHCH2N<), 1.45 - 1.22 (m, 72H, -CH2CH2CH2-, -CH2CH3), 0.88 (t, 12H, -CH2CH3). MS (ESI): m / z = 1022.9 ([M+H] + )。 Example 11: Cationic Lipid (E11-1) The preparation process is as follows: Under nitrogen protection, compound S9-3 (0.29 g, 1.0 mmol) was dissolved in acetonitrile (30 mL). S8-3 (2.09 g, 6.0 mmol) and DIPEA (0.65 g, 5.0 mmol) were successively added under slow stirring, and the mixture was stirred at room temperature for about 20 h. After the reaction was completed, the reaction solution was concentrated, then dissolved in dichloromethane, and extracted successively with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution. The organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. The crude product was purified by column chromatography to obtain cationic lipid E11-1 (1.12 g). 1 1H NMR (400 MHz, CDCl3) δ: 4.18 - 4.10 (m, 8H, -C(=O)OCH2-), 3.46 - 3.33 (m, 4H, pip-CH2CH2-), 3.04 (s, 4H, -NHC(=O)CH2-), 2.78 - 2.31 (m, 20H; 4H, pip-CH2CH2-; 8H, pip-H; 8H, >NCH2CH2-), 2.18 - 2.10 (m, 8H, -CH2CH2C(=O)O-), 1.84 - 1.76 (m, 8H, -C(=O)OCH2CH2-), 1.64 - 1.22 (m, 88H, -CH2CH2CH2-, -CH2CH3), 0.89 (t, 12H, -CH2CH3). MS (ESI): m / z = 1359.2 ([M+H] + )。 Example 12: Cationic Lipid (E12-1) The preparation process is as follows: Step a: Dissolve N-Boc-2-(2-bromoethoxy)ethylamine (S12-2, 5.36 g, 20.0 mmol) and piperazine (S12-1, 0.69 g, 8.0 mmol) in acetonitrile (100 mL). After adding potassium carbonate (7.73 g, 56.0 mmol) to the above system, heat it to 60 °C and stir for reaction for 3 h. After the reaction is completed, filter the reaction solution after it cools to room temperature, concentrate the filtrate, and purify the residue by column chromatography to obtain S12-3 (2.09 g). Step b: 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 a dichloromethane solution of S12-3 (1.84 g, 4.0 mmol) dropwise under an ice bath condition, and react at room temperature for 2 hours. 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 S12-4 (0.96 g, 92.2%) containing a naked amino group. Step c: To a round-bottom flask containing S1-2 (1.57 g, 9.0 mmol) and DIPEA (1.61 g, 9.0 mmol) dissolved in dichloromethane, add EDCI (1.72 g, 9.0 mmol) and HOBt (1.22 g, 9.0 mmol) in sequence, react at room temperature for 10 minutes, and then add S12-4 (0.78 g, 3.0 mmol) in batches, and stir the reaction solution at room temperature for 12 h. After the reaction is completed, add saturated NaHCO3 (10 mL) to quench the reaction, extract the aqueous phase with dichloromethane three times (20 mL * 3), dry the organic phase with anhydrous magnesium sulfate, filter, concentrate the filtrate, and purify the crude product by column chromatography to obtain S12-5 (0.98 g). Step d: 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 a dichloromethane solution of S12-5 (0.69 g, 1.2 mmol) dropwise under an ice bath condition, and react at room temperature for 2 hours. 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 S12-6 (0.42 g, 93.1%) containing a naked amino group. Step e: Dissolve S12-6 (0.30 g, 0.8 mmol) in isopropanol, add sufficient anhydrous potassium carbonate under stirring, and stir at room temperature until the reaction solution becomes alkaline. Add S6-1 (1.15 g, 4.8 mmol) to the reaction solution, and place the reaction solution in a reflux device (90 °C) and continue to stir and react for 36 h. After the reaction is completed, concentrate the reaction solution, and purify the crude product by column chromatography to obtain the cationic lipid E12-1 (0.82 g). 11H NMR (400 MHz, CDCl3) δ: 4.17 - 4.11 (m, 8H, -C(=O)OCH2-), 3.58 (t, 4H, -C(=O)NHCH2CH2O-), 3.51 (t, 4H, pip-CH2CH2-), 3.48 - 3.41 (m, 4H, -C(=O)NHCH2CH2O-), 3.03 (s, 4H, -NHC(=O)CH2-), 2.76 - 2.47 (m, 12H; 8H, pip-H; 4H, pip-CH2CH2-), 2.45 - 2.43 (m, 8H, >NCH2CH2-), 2.29 (t, 8H, -CH2C(=O)O-), 1.84 - 1.76 (m, 8H, -C(=O)OCH2CH2-), 1.68 - 1.23 (m, 72H, -CH2CH2CH2-, -CH2CH3), 0.87 (t, 12H, -CH2CH3). MS (ESI): m / z = 1335.1 ([M + H] + )。 Example 13: Cationic Lipid (E13-1) The preparation process is as follows: S12-6 (0.45 g, 1.2 mmol) and DIPEA (0.46 g, 3.6 mmol) were successively added to the methanol solution of S7-1 (1.32 g, 7.2 mmol), and the reaction solution was placed in a reflux device (90 °C) and continuously stirred for reaction for 24 h. After the reaction was completed, the reaction solution was concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E13-1 (0.91 g). 1 1H NMR (400 MHz, CDCl3) δ: 3.70 - 3.18 (m, 20H; 8H, -CH2OCH2-; 4H, -CH(OH)-; 4H, -CH2NHC(=O)-; 4H, -NHC(=O)CH2-), 2.77 - 2.31 (m, 20H; 4H, pip-CH2CH2-; 8H, pip-H; 8H, >CHCH2N<), 1.44 - 1.23 (m, 72H, -CH2CH2CH2-, -CH2CH3), 0.88 (t, 12H, -CH2CH3). MS (ESI): m / z = 1112.0 ([M + H] + )。 Example 14: Cationic Lipid (E14-1) The preparation process is as follows: Under nitrogen protection, compound S12-6 (0.37 g, 1.0 mmol) was dissolved in acetonitrile (30 mL). Under slow stirring, S8-3 (2.09 g, 6.0 mmol) and DIPEA (0.65 g, 5.0 mmol) were added successively, and the reaction was stirred at room temperature for about 20 h. After the reaction was completed, the reaction solution was concentrated, then dissolved in dichloromethane, and extracted successively with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution. The organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. The crude product was purified by column chromatography to obtain cationic lipid E14-1 (1.18 g). 1 H NMR (400 MHz, CDCl3) δ: 4.05 (t, 8H, -C(=O)OCH2-), 3.59 (t, 4H, -C(=O)NHCH2CH2O-), 3.52 (t, 4H, pip-CH2CH2-), 3.49 - 3.41 (m, 4H, -C(=O)NHCH2CH2O-), 3.03 (s, 4H, -NHC(=O)CH2-), 2.76 - 2.46 (m, 12H; 8H, pip-H; 4H, pip-CH2CH2-), 2.45 - 2.43 (m, 8H, >NCH2CH2-), 2.29 (t, 8H, -CH2C(=O)O-), 1.66 - 1.23 (m, 96H, -CH2CH2CH2-, -CH2CH3), 0.88 (t, 12H, -CH2CH3). MS (ESI): m / z = 1448.1 ([M+H] + )。 Example 15: Cationic Lipid (E15-1) The preparation process is as follows: Step a: 5-Bromopentanol (S15-1, 0.84 g, 5.0 mmol) was dissolved in 40 mL of dichloromethane, DMAP (1.22 g, 10 mmol) was added, and then phenyl chloroformate p-nitro (1.11 g, 5.5 mmol) was added in batches. The reaction was stirred at room temperature for 3 h. S8-2 (0.97 g, 5.6 mmol) was added to the reaction solution, and the reaction was continued to stir at room temperature overnight. After the reaction was completed, 20 mL of dichloromethane was added for dilution, and then washed with 30 mL of saturated brine. The organic phase was dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. The crude product was purified by column chromatography to obtain 5-bromopentyl undecyl carbonate (S15-2, 2.11 g). Step b: Under nitrogen protection, dissolve compound S1-3 (0.23 g, 0.8 mmol) in acetonitrile (30 mL). Sequentially add S15-2 (1.75 g, 4.8 mmol) and DIPEA (0.52 g, 4.0 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, and extract it sequentially 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 cationic lipid E15-1 (0.94 g). 1 H NMR (400 MHz, CDCl3) δ: 4.24 (t, 4H, pip-CH2CH2-), 4.15 - 4.10 (m, 16H, -CH2OC(=O)OCH2-), 3.36 (s, 4H, -OC(=O)CH2N<), 2.85 - 2.43 (m, 20H; 8H, pip-H; 4H, pip-CH2CH2-; 8H, >NCH2CH2-), 1.62 - 1.22 (m, 96H, -CH2CH2CH2-, -CH2CH3), 0.88 (t, 12H, -CH2CH3). MS (ESI): m / z=1425.1 ([M+H] + )。 Example 16: Cationic Lipid (E16-1) The preparation process is as follows: Step a: Dissolve S8-2 (2.06 g, 12.0 mmol) in dichloromethane (40 mL). Sequentially add triethylamine (5 mL) and N,N'-carbonyldiimidazole (CDI, 1.94 g, 12.0 mmol), and react at 50 °C for 1.5 h. Then add 4-amino-1-butanol (S16-1, 1.60 g, 18.0 mmol), and continue to react at 50 °C for 16 h. After the reaction is completed, cool the reaction solution to room temperature, wash it sequentially with 5% citric acid (20 mL * 2) and saturated brine (10 mL). Dry the organic phase with anhydrous magnesium sulfate, filter, and concentrate to obtain the crude product. Add dichloromethane (20 mL) to the crude product, stir for 10 min, filter, wash the residue with a small amount of dichloromethane, and concentrate to obtain compound S16-2 (2.26 g). Step b: Dissolve S16-2 (1.72 g, 6.0 mmol) in dichloromethane (80 mL), add triphenylphosphine (PPh3, 2.36 g, 9.0 mmol), and add carbon tetrabromide (CBr4, 2.98 g, 9.0 mmol) portionwise under an ice bath. React for 20 min under the ice bath. After the reaction is completed, add 10 mL of methanol to quench the reaction, directly concentrate to obtain the crude product, and purify the crude product by column chromatography to obtain the product S16-3 (1.23 g). Step c: Under nitrogen protection, dissolve compound S1-3 (0.14 g, 0.5 mmol) in acetonitrile (20 mL), and successively add S16-3 (1.05 g, 3.0 mmol) and DIPEA (0.32 g, 2.5 mmol) with slow stirring. Stir and react at room temperature for about 20 h. After the reaction is completed, concentrate the reaction solution, then dissolve it with 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 with anhydrous magnesium sulfate, filter, concentrate the filtrate, and purify the crude product by column chromatography to obtain the cationic lipid E16-1 (0.58 g). 1 H NMR (400 MHz, CDCl3) δ: 4.25 (t, 4H, pip-CH2CH2-), 4.11 (t, 8H, -NHC(=O)OCH2-), 3.35 (s, 4H, -OC(=O)CH2N<), 3.15 (t, 8H, -CH2NHC(=O)O-), 2.84 - 2.44 (m, 20H; 8H, pip-H; 4H, pip-CH2CH2-; 8H, >NCH2CH2-), 1.65 - 1.22 (m, 96H, -CH2CH2CH2-, -CH2CH3), 0.88 (t, 12H, -CH2CH3). MS (ESI): m / z = 1421.2 ([M+H] + )。 Example 17: Cationic Lipid (E17-1) The preparation process is as follows: Step a: Under nitrogen protection, add DCC (3.63 g, 17.6 mmol) to a round-bottom flask containing 2-decen-1-ol (S17-1, 1.36 g, 9.6 mmol), S8-1 (1.56 g, 8.0 mmol), and DMAP (0.24 g, 2.0 mmol) dissolved in dichloromethane (20 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 S17-2 (2.11 g). Step b: Under nitrogen protection, dissolve compound S1-3 (0.29 g, 1.0 mmol) in acetonitrile (30 mL). Sequentially add S17-2 (1.91 g, 6.0 mmol) and DIPEA (0.65 g, 5.0 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, and 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 (1.01 g). 1 H NMR(400MHz,CDCl3)δ:5.82-5.71(m,4H,-C(=O)OCH2CH=CH-),5.56-5.54(m,4H,-C(=O)OCH2CH=CH-),4.24(t,4H,pip-CH2CH2-),4.55(t,8H,-C(=O)OCH2CH=CH-),3.36(s,4H,-OC(=O)CH2N<),2.85-2.43(m,20H;8H,pip-H;4H,pip-CH2CH2-;8H,>NCH2CH2-),2.18-2.10(m,8H,-CH2CH2C(=O)O-),2.06-1.99(m,8H,-CH=CHCH2CH2-),1.64-1.22(m,56H,-CH2CH2CH2-,-CH2CH3),0.88(t,12H,-CH2CH3). MS(ESI):m / z=1241.0([M+H] + )。 Example 18: Cationic Lipid (E18-1) Replace the raw material S1-3 in step b of Example 15 with the raw material S9-3 (0.29 g, 1.0 mmol), and prepare according to the same reaction steps to obtain cationic lipid E18-1 (1.18 g). 1 H NMR(400MHz,CDCl3)δ:4.15-4.10(m,16H,-CH2OC(=O)OCH2-),3.46-3.33(m,4H,pip-CH2CH2-),3.04(s,4H,-NHC(=O)CH2-),2.78-2.32(m,20H;4H,pip-CH2CH2-;8H,pip-H;8H,>NCH2CH2-),1.60-1.22(m,96H,-CH2CH2CH2-,-CH2CH3),0.89(t,12H,-CH2CH3). MS(ESI):m / z=1423.2([M+H]+ )。 Example 19: Cationic Lipid (E19-1) Replace the raw material S1-3 in step c of Example 16 with raw material S9-3 (0.29 g, 1.0 mmol), and prepare according to the same reaction steps to obtain cationic lipid E19-1 (1.17 g). 1 H NMR (400 MHz, CDCl3) δ: 4.11 (t, 8H, -NHC(=O)OCH2-), 3.46 - 3.33 (m, 4H, pip-CH2CH2-), 3.28 (s, 4H, -NHC(=O)CH2-), 3.15 (t, 8H, -CH2NHC(=O)O-), 2.84 - 2.42 (m, 20H; 8H, pip-H; 4H, pip-CH2CH2-; 8H, >NCH2CH2-), 1.62 - 1.22 (m, 96H, -CH2CH2CH2-,-CH2CH3), 0.89 (t, 12H, -CH2CH3). MS(ESI): m / z=1419.2([M+H] + )。 Example 20: Cationic Lipid (E20-1) Replace the raw material S1-3 in step b of Example 17 with raw material S9-3 (0.37 g, 1.0 mmol), and prepare according to the same reaction steps to obtain cationic lipid E20-1 (1.03 g). 1 H NMR (400 MHz, CDCl3) δ: 5.82 - 5.70 (m, 4H, -C(=O)OCH2CH=CH-), 5.56 - 5.53 (m, 4H, -C(=O)OCH2CH=CH-), 4.55 (t, 8H, -C(=O)OCH2CH=CH-), 3.46 - 3.33 (m, 4H, pip-CH2CH2-), 3.27 (s, 4H, -NHC(=O)CH2-), 2.85 - 2.43 (m, 20H; 8H, pip-H; 4H, pip-CH2CH2-; 8H, >NCH2CH2-), 2.18 - 2.10 (m, 8H, -CH2CH2C(=O)O-), 2.06 - 1.99 (m, 8H, -CH=CHCH2CH2-), 1.64 - 1.22 (m, 56H, -CH2CH2CH2-,-CH2CH3), 0.89 (t, 12H, -CH2CH3). MS(ESI): m / z=1239.0([M+H] + )。 Example 21: Cationic Lipid (E21-1) Replace the raw material S1-3 in step b of Example 15 with the raw material S12-6 (0.37 g, 1.0 mmol), and prepare according to the same reaction steps to obtain the cationic lipid E21-1 (1.26 g). 1 H NMR (400 MHz, CDCl3) δ: 4.15 - 4.10 (m, 16H, -CH2OC(=O)OCH2-), 3.59 (t, 4H, -C(=O)NHCH2CH2O-), 3.52 (t, 4H, pip-CH2CH2-), 3.49 - 3.41 (m, 4H, -C(=O)NHCH2CH2O-), 3.03 (s, 4H, -NHC(=O)CH2-), 2.76 - 2.47 (m, 12H; 8H, pip-H; 4H, pip-CH2CH2-), 2.46 - 2.43 (m, 8H, >NCH2CH2-), 1.62 - 1.22 (m, 96H, -CH2CH2CH2-, -CH2CH3), 0.88 (t, 12H, -CH2CH3). MS (ESI): m / z=1511.2 ([M+H] + ) Example 22: Cationic Lipid (E22-1) Replace the raw material S1-3 in step c of Example 16 with the raw material S12-6 (1.37 g, 1.0 mmol), and prepare according to the same reaction steps to obtain the cationic lipid E22-1 (1.24 g). 1 H NMR (400 MHz, CDCl3) δ: 4.10 (t, 8H, -NHC(=O)OCH2-), 3.59 (t, 4H, -C(=O)NHCH2CH2O-), 3.52 (t, 4H, pip-CH2CH2-), 3.49 - 3.41 (m, 4H, -C(=O)NHCH2CH2O-), 3.15 (t, 8H, -CH2NHC(=O)O-), 3.03 (s, 4H, -NHC(=O)CH2-), 2.77 - 2.47 (m, 12H; 8H, pip-H; 4H, pip-CH2CH2-), 2.46 - 2.43 (m, 8H, >NCH2CH2-), 1.62 - 1.22 (m, 96H, -CH2CH2CH2-, -CH2CH3), 0.88 (t, 12H, -CH2CH3). MS (ESI): m / z=1507.3 ([M+H] + ) Example 23: Cationic Lipid (E23-1) Replace the raw material S1-3 in step b of Example 17 with the raw material S12-6 (0.37 g, 1.0 mmol), and prepare according to the same reaction steps to obtain the cationic lipid E23-1 (1.10 g). 1 H NMR (400 MHz, CDCl3) δ: 5.82 - 5.71 (m, 4H, -C(=O)OCH2CH=CH-), 5.56 - 5.54 (m, 4H, -C(=O)OCH2CH=CH-), 4.55 (t, 8H, -C(=O)OCH2CH=CH-), 3.59 (t, 4H, -C(=O)NHCH2CH2O-), 3.52 (t, 4H, pip-CH2CH2-), 3.48 - 3.42 (m, 4H, -CH2NHC(=O)-), 3.04 (s, 4H, -NHC(=O)CH2-), 2.76 - 2.48 (m, 12H; 8H, pip-H; 4H, pip-CH2CH2-), 2.46 - 2.43 (m, 8H, >NCH2CH2-), 2.28 (t, 8H, -CH2C(=O)O-), 2.07 - 1.99 (m, 8H, -CH=CHCH2CH2-), 1.62 - 1.22 (m, 56H, -CH2CH2CH2-,-CH2CH3), 0.88 (t, 12H, -CH2CH3). MS (ESI): m / z=1327.0 ([M+H] + )。 Example 24: Cationic Lipid (E24-1) The preparation process is as follows: Step a: Dissolve 2-(2-bromoethoxy)ethanol (S24-1, 2.54 g, 15.0 mmol) and S12-1 (0.52 g, 6.0 mmol) in acetonitrile (80 mL). After adding potassium carbonate (5.80 g, 42.0 mmol) to the above system, heat to 60 °C and stir for 3 h. After the reaction is completed, filter the reaction solution after cooling to room temperature, concentrate the filtrate, and purify the residue by column chromatography to obtain S24-2 (0.90 g). Step b: Add S24-2 (0.79 g, 3.0 mmol), p-toluenesulfonic acid (0.57 g, 3.3 mmol) and anhydrous toluene (20 mL) into a round-bottom flask. 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 S1-2 (1.10 g, 6.3 mmol) in batches, and heat to 135 °C for 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, dry it with anhydrous magnesium sulfate, filter, concentrate the filtrate, and purify the crude product by column chromatography to obtain compound S24-3 (1.12 g). Step c: Remove the Boc protecting group. Prepare a solution of trifluoroacetic acid / dichloromethane (1:2, v / v) in a dry and clean round-bottom flask. Slowly add a dichloromethane solution of S24-3 (0.69 g, 1.2 mmol) dropwise under an ice bath condition 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 S24-4 (0.42 g, 92.9%) with an exposed amino group. Step d: Under nitrogen protection, dissolve compound S24-4 (0.38 g, 1.0 mmol) in acetonitrile (30 mL), and successively add S17-2 (1.91 g, 6.0 mmol) and DIPEA (0.65 g, 5.0 mmol) with 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, 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 cationic lipid E24-1 (1.10 g). 11H NMR (400 MHz, CDCl3) δ: 5.82 - 5.70 (m, 4H, -C(=O)OCH2CH=CH-), 5.56 - 5.54 (m, 4H, -C(=O)OCH2CH=CH-), 4.55 (t, 8H, -C(=O)OCH2CH=CH-), 4.25 (t, 4H, -OCH2CH2OC(=O)-), 3.70 - 3.54 (m, 8H; 4H, -OCH2CH2OC(=O)-; 4H, pip-CH2CH2-), 3.44 (s, 4H, -OC(=O)CH2N<), 2.98 (t, 8H, >NCH2(CH2)4-), 2.84 - 2.34 (t, 12H; 4H, pip-CH2CH2-; 8H, pip-H), 2.29 (t, 8H, -CH2C(=O)O-), 2.06 - 1.99 (m, 8H, -CH=CHCH2CH2-), 1.65 - 1.22 (m, 56H, -CH2CH2CH2-,-CH2CH3), 0.89 (t, 12H, -CH2CH3). MS (ESI): m / z=1329.0 ([M+H] + )。 Example 25: Cationic Lipid (E25-1) The preparation process is as follows: Dissolve S24-4 (0.38 g, 1.0 mmol) in isopropanol, add sufficient anhydrous potassium carbonate under stirring, and stir at room temperature until the reaction solution becomes alkaline. Then add S6-1 (1.44 g, 6.0 mmol) to the reaction solution, and place the reaction solution in a reflux device (90 °C) and continue stirring for 36 h. After the reaction is completed, concentrate the reaction solution, and the crude product is purified by column chromatography to obtain cationic lipid E25-1 (1.04 g). 1 1H NMR (400 MHz, CDCl3) δ: 4.24 (t, 4H, -OCH2CH2OC(=O)-), 4.05 (t, 8H, -C(=O)OCH2), 3.70 - 3.54 (m, 8H; 4H, -OCH2CH2OC(=O)-; 4H, pip-CH2CH2-), 3.44 (s, 4H, -OC(=O)CH2N<), 2.98 (t, 8H, >NCH2CH2C(=O)O-), 2.84 - 2.34 (t, 20H; 8H, -CH2C(=O)O-; 4H, pip-CH2CH2-; 8H, pip-H), 1.63 - 1.26 (m, 80H, -CH2CH2CH2-,-CH2CH3), 0.88 (t, 12H, -CH2CH3). MS (ESI): m / z=1337.9 ([M+H]+ )。 Example 26: Cationic Lipid (E26-1) The preparation process is as follows: Step a: Under nitrogen protection, DCC (3.63 g, 17.6 mmol) was added to a round-bottom flask containing 5-hexen-1-ol (S26-2, 1.38 g, 8.0 mmol), n-decanoic acid (S26-1, 0.96 g, 9.6 mmol) and DMAP (0.24 g, 2.0 mmol) dissolved in dichloromethane (30 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 S26-3 (1.65 g). Step b: Compound S26-3 (1.27 g, 5.0 mmol) was dissolved in 20 mL of dichloromethane, and m-chloroperbenzoic acid (m-CPBA, 1.29 g, 7.5 mmol) was added under ice bath conditions. After stirring for 15 min, the ice bath was removed and the reaction was stirred overnight. After the reaction was completed, an excess of saturated sodium bisulfite solution was added to consume the unreacted m-CPBA, and dichloromethane was removed by concentration. Then, 20 mL of ethyl acetate and 20 mL of saturated sodium bicarbonate solution were added successively and washed 3 times, and 20 mL of saturated sodium chloride solution was washed once. The organic phase was dried over anhydrous magnesium sulfate, filtered, the reaction solution was concentrated, and the crude product was purified by column chromatography to obtain compound S26-4 (1.00 g). Step c: S1-3 (0.29 g, 1.0 mmol) and DIPEA (0.39 g, 3.0 mmol) were successively added to the methanol solution of S26-4 (1.62 g, 6.0 mmol), and the reaction solution was placed in a reflux device (90 °C) and stirred for 24 h. After the reaction was completed, the reaction solution was concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E26-1 (0.92 g). 11H NMR (400 MHz, CDCl3) δ: 4.24 (t, 4H, pip-CH2CH2-), 4.17 - 4.14 (t, 8H, -CH2OC(=O)-), 3.51 - 3.42 (m, 4H, -CH(OH)-), 3.33 (s, 4H, -OC(=O)CH2N<), 2.78 - 2.31 (m, 20H; 4H, pip-CH2CH2-; 8H, pip-H; 8H, >CHCH2N<), 2.18 - 2.10 (m, 8H, -CH2CH2C(=O)O-), 1.84 - 1.76 (m, 8H, -C(=O)OCH2CH2-), 1.64 - 1.22 (m, 72H, -CH2CH2CH2-, -CH2CH3), 0.87 (t, 12H, -CH2CH3). MS (ESI): m / z = 1369.1 ([M+H] + )。 Example 27: Cationic Lipid (E27-1) The preparation process is as follows: S9-3 (0.34 g, 1.2 mmol) and DIPEA (0.46 g, 3.6 mmol) were successively added to the methanol solution of S26-4 (1.94 g, 7.2 mmol), and the reaction solution was placed in a reflux device (90 °C) and continuously stirred for reaction for 24 h. After the reaction was completed, the reaction solution was concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E27-1 (1.09 g). 1 1H NMR (400 MHz, CDCl3) δ: 4.17 - 4.14 (m, 8H, -CH2OC(=O)-), 3.51 - 3.33 (m, 8H; 4H, -CH(OH)-; 4H, pip-CH2CH2-), 3.04 (s, 4H, -NHC(=O)CH2-), 2.79 - 2.31 (m, 20H; 4H, pip-CH2CH2-; 8H, pip-H; 8H, >CHCH2N<), 2.18 - 2.10 (m, 8H, -CH2CH2C(=O)O-), 1.84 - 1.76 (m, 8H, -C(=O)OCH2CH2-), 1.64 - 1.22 (m, 72H, -CH2CH2CH2-, -CH2CH3), 0.88 (t, 12H, -CH2CH3). MS (ESI): m / z = 1367.1 ([M+H] + )。 Example 28: Cationic Lipid (E28-1) Replace the raw material S9-3 in Example 27 with raw material S12-6 (1.51 g, 7.2 mmol), and prepare according to the same reaction steps to obtain cationic lipid E28-1 (1.19 g). 1 H NMR (400 MHz, CDCl3) δ: 4.07 - 4.00 (m, 8H, -CH2OC(=O)-), 3.72 - 3.39 (m, 16H; 8H, -CH2OCH2-; 4H, -CH(OH)-; 4H, -CH2NHC(=O)-), 3.31 - 3.19 (m, 4H, -NHC(=O)CH2-), 2.82 - 2.33 (m, 20H; 4H, pip-CH2CH2-; 8H, >CHCH2N<; 8H, pip-H), 2.27 (t, 8H, -CH2C(=O)O-), 1.67 - 1.19 (m, 80H, -CH2CH2CH2-,-CH2CH3), 0.88 (t, 12H, -CH2CH3). MS(ESI): m / z=1455.8 ([M+H] + )。 Example 29: Cationic Lipid (E29-1) Replace the raw material S1-3 in step c of Example 1 with raw material S9-3 (0.29 g, 1.0 mmol), and prepare according to the same reaction steps to obtain cationic lipid E29-1 (1.09 g). 1 H NMR (400 MHz, CDCl3) δ: 4.17 - 4.11 (m, 8H, -C(=O)OCH2-), 3.46 - 3.33 (m, 4H, pip-CH2CH2-), 3.03 (s, 4H, -NHC(=O)CH2-), 2.84 - 2.42 (m, 20H; 8H, pip-H; 4H, pip-CH2CH2-; 8H, >NCH2CH2-), 2.33 - 2.20 (m, 16H, -CH2C≡CCH2(CH2)2CH3), 2.18 - 2.11 (m, 8H, -CH2CH2C(=O)O-), 1.84 - 1.76 (m, 8H, -C(=O)OCH2CH2CH2-), 1.64 - 1.22 (m, 56H, -CH2CH2CH2-,-CH2CH3), 0.89 (t, 12H, -CH2CH3). MS(ESI): m / z=1343.1 ([M+H] + )。 Example 30: Cationic Lipid (E30-1) Replace the raw material S1-3 in step c of Example 1 with raw material S12-6 (0.37 g, 1.0 mmol), and prepare according to the same reaction steps to obtain cationic lipid E30-1 (1.17 g). 1 H NMR (400 MHz, CDCl3) δ: 4.18 - 4.10 (m, 8H, -C(=O)OCH2-), 3.59 (t, 4H, -C(=O)NHCH2CH2O-), 3.52 (t, 4H, pip-CH2CH2-), 3.48 - 3.42 (m, 4H, -CH2NHC(=O)-), 3.04 (s, 4H, -NHC(=O)CH2N<), 2.84 - 2.42 (m, 20H; 8H, pip-H; 4H, pip-CH2CH2-; 8H, >NCH2CH2-), 2.33 - 2.20 (m, 16H, -CH2C≡CCH2(CH2)2CH3), 2.18 - 2.11 (m, 8H, -CH2CH2C(=O)O-), 1.84 - 1.76 (m, 8H, -C(=O)OCH2CH2CH2-), 1.64 - 1.21 (m, 56H, -CH2CH2CH2-,-CH2CH3), 0.89 (t, 12H, -CH2CH3). MS (ESI): m / z=1431.1 ([M+H] + )。 Example 31: Cationic lipid (E31-1) Replace the raw material S1-3 in Example 2 with raw material S9-3 (0.29 g, 1.0 mmol), and prepare according to the same reaction steps to obtain cationic lipid E31-1 (1.19 g). 1 H NMR (400 MHz, CDCl3) δ: 5.45 - 5.26 (m, 16H, -CH=CH-), 3.46 - 3.33 (m, 4H, pip-CH2CH2-), 3.03 (s, 4H, -NHC(=O)CH2-), 2.82 - 2.43 (m, 28H; 8H, pip-H; 4H, pip-CH2CH2-; 8H, >NCH2CH2-; 8H, -CH=CHCH2CH=CH-), 2.03 - 1.97 (m, 16H, -CH=CHCH2-), 1.64 - 1.22 (m, 72H, -CH2CH2CH2-,-CH2CH3), 0.89 (t, 12H, -CH2CH3). MS (ESI): m / z=1279.2 ([M+H] + )。 Example 32: Cationic lipid (E32-1) Replace the raw material S1-3 in Example 2 with the raw material S12-6 (0.37 g, 1.0 mmol), and prepare according to the same reaction steps to obtain the cationic lipid E32-1 (1.26 g). 1 H NMR (400 MHz, CDCl3) δ: 5.45 - 5.24 (m, 16H, -CH=CH-), 3.59 (t, 4H, -C(=O)NHCH2CH2O-), 3.52 (t, 4H, pip-CH2CH2-), 3.48 - 3.42 (m, 4H, -CH2NHC(=O)-), 3.04 (s, 4H, -NHC(=O)CH2-), 2.81 - 2.43 (m, 28H; 8H, pip-H; 4H, pip-CH2CH2-; 8H, >NCH2CH2-; 8H, -CH=CHCH2CH=CH-), 2.05 - 1.97 (m, 16H, -CH=CHCH2-), 1.64 - 1.22 (m, 72H, -CH2CH2CH2-,-CH2CH3), 0.89 (t, 12H, -CH2CH3). MS(ESI): m / z=1367.3 ([M+H] + )。 Example 33: Cationic lipid (E33-1) Replace the raw material S1-3 in step b of Example 3 with the raw material S9-3 (0.29 g, 1.0 mmol), and prepare according to the same reaction steps to obtain the cationic lipid E33-1 (1.21 g). 1 H NMR (400 MHz, CDCl3) δ: 5.45 - 5.24 (m, 16H, -CH=CH-), 4.16 - 4.09 (m, 8H, -C(=O)OCH2-), 3.46 - 3.34 (m, 4H, pip-CH2CH2-), 3.03 (s, 4H, -NHC(=O)CH2-), 2.83 - 2.43 (m, 28H; 8H, pip-H; 4H, pip-CH2CH2-; 8H, >NCH2CH2-; 8H, -CH=CHCH2CH=CH-), 2.23 (t, 8H, -CH2CH2C(=O)O-), 2.03 - 1.97 (m, 16H, -CH=CHCH2-), 1.84 - 1.76 (m, 8H, -C(=O)OCH2CH2CH2-), 1.64 - 1.22 (m, 64H, -CH2CH2CH2-,-CH2CH3), 0.89 (t, 12H, -CH2CH3). MS(ESI): m / z=1567.3 ([M+H] + )。 Example 34: Cationic Lipid (E34-1) Replace the raw material S1-3 in step b of Example 3 with raw material S12-6 (0.37 g, 1.0 mmol), and prepare according to the same reaction steps to obtain cationic lipid E34-1 (1.28 g). 1 H NMR (400 MHz, CDCl3) δ: 5.44 - 5.24 (m, 16H, -CH=CH-), 4.16 - 4.10 (m, 8H, -C(=O)OCH2-), 3.59 (t, 4H, -C(=O)NHCH2CH2O-), 3.52 (t, 4H, pip-CH2CH2-), 3.48 - 3.42 (m, 4H, -CH2NHC(=O)-), 3.04 (s, 4H, -NHC(=O)CH2-), 2.81 - 2.43 (m, 28H; 8H, pip-H; 4H, pip-CH2CH2-; 8H, >NCH2CH2-; 8H, -CH=CHCH2CH=CH-), 2.23 (t, 8H, -CH2CH2C(=O)O-), 2.03 - 1.97 (m, 16H, -CH=CHCH2-), 1.82 - 1.76 (m, 8H, -C(=O)OCH2CH2CH2-), 1.64 - 1.20 (m, 64H, -CH2CH2CH2-,-CH2CH3), 0.87 (t, 12H, -CH2CH3). MS (ESI): m / z=1655.4 ([M+H] + )。 Example 35: Cationic Lipid (E35-1) Replace the raw material S1-3 in Example 4 with raw material S9-3 (0.29 g, 1.0 mmol), and prepare according to the same reaction steps to obtain cationic lipid E35-1 (0.94 g). 1 H NMR (400 MHz, CDCl3) δ: 3.46 - 3.33 (m, 4H, pip-CH2CH2-), 3.28 (dd, 8H, -C(=O)NHCH2(CH2) 10-), 3.03 (s, 4H, -NHC(=O)CH2N<), 2.82 - 2.62 (m, 20H; 8H, pip-H; 4H, pip-CH2CH2-; 8H, >NCH2CH2-), 2.37 (t, 8H, >NCH2CH2-), 1.65 - 1.22 (m, 80H, -CH2CH2CH2-, -CH2CH3), 0.89 (t, 12H, -CH2CH3). MS(ESI): m / z=1243.1 ([M+H] + )。 Example 36: Cationic Lipid (E36-1) Replace the raw material S1-3 in Example 4 with raw material S12-6 (0.37 g, 1.0 mmol), and prepare according to the same reaction steps to obtain cationic lipid E36-1 (1.00 g). 1 H NMR(400MHz,CDCl3)δ: 3.59 (t, 4H, -C(=O)NHCH2CH2O-), 3.52 (t, 4H, pip-CH2CH2-), 3.48 - 3.42 (m, 4H, -CH2NHC(=O)-), 3.28 (dd, 8H, -C(=O)NHCH2(CH2) 10 -), 3.04 (s, 4H, -NHC(=O)CH2N<), 2.81 - 2.62 (m, 20H; 8H, pip-H; 4H, pip-CH2CH2-; 8H, >NCH2CH2-), 2.39 (t, 8H, >NCH2CH2-), 1.64 - 1.22 (m, 80H, -CH2CH2CH2-, -CH2CH3), 0.86 (t, 12H, -CH2CH3). MS(ESI): m / z=1331.2 ([M+H] + )。 Example 37: Cationic Lipid (E37-1) Replace the raw material S1-3 in step b of Example 5 with raw material S9-3 (0.29 g, 1.0 mmol), and prepare according to the same reaction steps to obtain cationic lipid E37-1 (1.09 g). 11H NMR (400 MHz, CDCl3) δ: 4.17 - 4.11 (m, 8H, -C(=O)OCH2-), 3.46 - 3.33 (m, 4H, pip-CH2CH2-), 3.28 (dd, 8H, -C(=O)NHCH2(CH2)3-), 3.03 (s, 4H, -NHC(=O)CH2N<), 2.82 - 2.62 (m, 20H; 8H, pip-H; 4H, pip-CH2CH2-; 8H, >NCH2CH2-), 2.39 (t, 8H, -CH2C(=O)NH-), 2.18 - 2.11 (m, 8H, -CH2CH2C(=O)O-), 1.84 - 1.76 (m, 8H, -C(=O)OCH2CH2CH2-), 1.64 - 1.22 (m, 56H, -CH2CH2CH2-, -CH2CH3), 0.89 (t, 12H, -CH2CH3). MS (ESI): m / z=1419.1 ([M+H] + )。 Example 38: Cationic Lipid (E38-1) Replace the raw material S1-3 in step b of Example 5 with raw material S12-6 (0.37 g, 1.0 mmol), and prepare according to the same reaction steps to obtain cationic lipid E38-1 (1.16 g). 1 1H NMR (400 MHz, CDCl3) δ: 4.18 - 4.12 (m, 8H, -C(=O)OCH2-), 3.59 (t, 4H, -C(=O)NHCH2CH2O-), 3.52 (t, 4H, pip-CH2CH2-), 3.48 - 3.42 (m, 4H, -CH2NHC(=O)-), 3.28 (dd, 8H, -C(=O)NHCH2(CH2)3-), 3.03 (s, 4H, -NHC(=O)CH2N<), 2.81 - 2.62 (m, 20H; 8H, pip-H; 4H, pip-CH2CH2-; 8H, >NCH2CH2-), 2.39 (t, 8H, >NCH2CH2-), 2.18 - 2.11 (m, 8H, -CH2CH2C(=O)O-), 1.84 - 1.76 (m, 8H, -C(=O)OCH2CH2CH2-), 1.642 - 1.20 (m, 56H, -CH2CH2CH2-, -CH2CH3), 0.89 (t, 12H, -CH2CH3). MS (ESI): m / z=1507.1 ([M+H] + )。 Example 39: Cationic Lipid (E39-1) The preparation process is as follows: Step a: Under nitrogen protection, DCC (6.80 g, 33.0 mmol) was added to a round-bottom flask containing S39-1 (1.52 g, 5.0 mmol, S39-1 was obtained by reacting 1,4,7-triazacyclononane with bromoacetic acid , tert-butyldimethylsilylethoxymethanol (S39-2, 3.08 g, 17.5 mmol) and DMAP (0.49 g, 4.0 mmol) dissolved in dichloromethane (100 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, the residue was dissolved in THF (10 mL), under nitrogen protection, TBAF (10 mL, 1 M) was added, and 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, the filtrate was concentrated, and the crude product was purified by column chromatography to obtain S39-3 (1.62 g). Step b: Under nitrogen protection, DCC (4.08 g, 19.8 mmol) was added to a round-bottom flask containing S39-3 (1.31 g, 8.0 mmol), S1-2 (1.84 g, 10.5 mmol) and DMAP (0.29 g, 2.4 mmol) dissolved in dichloromethane (50 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, the residue was dissolved in dichloromethane solution, and slowly added dropwise to the prepared trifluoroacetic acid / dichloromethane (1:2, v / v) solution under ice bath conditions, and the reaction was carried out at room temperature for 2 h. 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 S39-4 (1.33 g). Step c: S39-4 (0.61 g, 1.0 mmol) was dissolved in isopropanol, sufficient anhydrous potassium carbonate was added with stirring, and stirred at room temperature until the reaction solution was alkaline. S6-1 (2.16 g, 9.0 mmol) was added to the reaction solution, and the reaction solution was placed in a reflux device (90 °C) and stirred for reaction for 36 h. After the reaction was completed, the reaction solution was concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E39-1 (1.55 g). 1 H NMR (400 MHz, CDCl3) δ: 4.27 - 4.09 (m, 24H; 12H, -C(=O)OCH2CH2OC(=O)-; 12H, -C(=O)OCH2(CH2) 10-), 3.36 (s, 6H, -OC(=O)CH2N<), 3.20 (s, 6H, Ring-CH2-), 2.84 - 2.43 (m, 24H; 12H, Ring-H; 12H, >NCH2CH2-), 2.18 - 2.10 (m, 12H, -CH2CH2C(=O)O-), 1.84 - 1.76 (m, 12H, -C(=O)OCH2CH2CH2-), 1.64 - 1.22 (m, 108H, -CH2CH2CH2-, -CH2CH3), 0.89 (t, 18H, -CH2CH3). MS(ESI): m / z=2047.5 ([M+H] + )。 Example 40: Cationic Lipid (E40-1) The preparation process is as follows: Under nitrogen protection, dissolve compound S39-4 (0.61 g, 1.0 mmol) in acetonitrile (30 mL). Sequentially add S8-3 (3.14 g, 9.0 mmol) and DIPEA (1.03 g, 8.0 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, and 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 E40-1 (1.11 g). 1 H NMR(400 MHz, CDCl3) δ: 4.27 - 4.09 (m, 24H; 12H, -C(=O)OCH2CH2OC(=O)-; 12H, -C(=O)OCH2(CH2) 10 -), 3.36 (s, 6H, -OC(=O)CH2N<), 3.20 (s, 6H, Ring-CH2-), 2.84 - 2.43 (m, 24H; 12H, Ring-H; 12H, >NCH2CH2-), 2.18 - 2.10 (m, 12H, -CH2CH2C(=O)O-), 1.84 - 1.76 (m, 12H, -C(=O)OCH2CH2CH2-), 1.64 - 1.22 (m, 132H, -CH2CH2CH2-, -CH2CH3), 0.89 (t, 18H, -CH2CH3). MS(ESI): m / z=2215.7 ([M+H] + )。 Example 41: Cationic Lipid (E41-1) The preparation process is as follows: S39-4 (0.73 g, 1.2 mmol) and DIPEA (0.70 g, 5.4 mmol) were successively added to a methanol solution of S7-1 (1.98 g, 10.8 mmol), and the reaction solution was placed in a reflux device (90 °C) and continuously stirred for reaction for 24 h. After the reaction was completed, the reaction solution was concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E41-1 (1.38 g). 1 HNMR (400 MHz, CDCl3) δ: 4.27 - 4.09 (m, 12H, -C(=O)OCH2CH2OC(=O)-), 3.51 - 3.41 (m, 6H, -CH(OH)-), 3.34 (s, 6H, -OC(=O)CH2N<), 3.20 (s, 6H, Ring-CH2-), 2.84 - 2.43 (m, 24H; 12H, Ring-H; 12H, >CHCH2N<), 1.44 - 1.23 (m, 108H, -CH2CH2CH2-, -CH2CH3), 0.89 (t, 18H, -CH2CH3). MS (ESI): m / z=1711.4 ([M+H] + )。 Example 42: Cationic lipid (E42-1) The preparation process is as follows: Under nitrogen protection, compound S39-4 (0.30 g, 0.5 mmol) was dissolved in acetonitrile (20 mL), and S16-3 (1.58 g, 4.5 mmol) and DIPEA (0.52 g, 4.0 mmol) were successively added under slow stirring, and the reaction was stirred at room temperature for about 20 h. After the reaction was completed, the reaction solution was concentrated, then dissolved in dichloromethane, and extracted successively with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution. The organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. The crude product was purified by column chromatography to obtain cationic lipid E42-1 (0.94 g). 11H NMR (400 MHz, CDCl3) δ: 4.27 - 4.09 (m, 24H; 12H, -C(=O)OCH2CH2OC(=O)-; 12H, -NHC(=O)OCH2-), 3.36 (s, 6H, -OC(=O)CH2N<), 3.20 (s, 6H, Ring-CH2-), 3.15 (t, 12H, -CH2NHC(=O)O-), 2.84 - 2.43 (m, 24H; 12H, Ring-H; 12H, >NCH2CH2-), 1.62 - 1.22 (m, 144H, -CH2CH2CH2-, -CH2CH3), 0.88 (t, 18H, -CH2CH3). MS (ESI): m / z = 2305.8 ([M+H] + )。 Example 43: Cationic Lipid (E43-1) The preparation process is as follows: Step a: Under nitrogen protection, DCC (9.06 g, 44.0 mmol) was added to a round-bottom flask containing S43-1 (2.02 g, 5.0 mmol), S39-2 (4.4 g, 25.0 mmol) and DMAP (0.61 g, 5.0 mmol) dissolved in dichloromethane (150 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, the residue was dissolved in THF (15 mL), and TBAF (15 mL, 1 M) was added under nitrogen protection, and 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, and the crude product was purified by column chromatography to obtain S43-2 (2.13 g). Step b: Under nitrogen protection, DCC (5.44 g, 26.4 mmol) was added to a round-bottom flask containing S43-2 (1.74 g, 8.0 mmol), S1-2 (2.63 g, 15.0 mmol) and DMAP (0.37 g, 3.0 mmol) dissolved in dichloromethane (50 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, the residue was dissolved in dichloromethane solution, and it was slowly added dropwise to the prepared trifluoroacetic acid / dichloromethane (1:2, v / v) solution under ice bath conditions, and the reaction was carried out at room temperature for 2 h. 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 S43-3 (1.76 g). Step c: Dissolve S43-3 (0.81 g, 1.0 mmol) in isopropanol, add an adequate amount of anhydrous potassium carbonate under stirring, and stir at room temperature until the reaction solution becomes alkaline. Add S6-1 (2.88 g, 12.0 mmol) to the reaction solution, and place the reaction solution in a reflux apparatus (90 °C) and continue stirring for reaction for 36 h. After the reaction is completed, concentrate the reaction solution, and the crude product is purified by column chromatography to obtain cationic lipid E43-1 (1.99 g). 1 H NMR (400 MHz, CDCl3) δ: 4.27 - 4.07 (m, 32H; 16H, -C(=O)OCH2CH2OC(=O)-; 16H, -C(=O)OCH2(CH2) 10 -), 3.36 (s, 8H, -OC(=O)CH2N<), 3.21 (s, 8H, Ring-CH2-), 2.84 - 2.43 (m, 32H; 16H, Ring-H; 16H, >NCH2CH2-), 2.19 - 2.10 (m, 16H, -CH2CH2C(=O)O-), 1.84 - 1.76 (m, 16H, -C(=O)OCH2CH2CH2-), 1.65 - 1.22 (m, 144H, -CH2CH2CH2-, -CH2CH3), 0.86 (t, 24H, -CH2CH3). MS (ESI): m / z=2730.1 ([M+H] + )。 Example 44: Cationic lipid (E44-1) The preparation process is as follows: Under nitrogen protection, dissolve compound S43-3 (0.81 g, 1.0 mmol) in acetonitrile (60 mL), and successively add S8-3 (4.19 g, 12.0 mmol) and DIPEA (1.29 g, 10.0 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 with 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 with anhydrous magnesium sulfate, filter, concentrate the filtrate, and the crude product is purified by column chromatography to obtain cationic lipid E44-1 (2.39 g). 1 H NMR (400 MHz, CDCl3) δ: 4.25 - 4.09 (m, 32H; 16H, -C(=O)OCH2CH2OC(=O)-; 16H, -C(=O)OCH2(CH2) 10-), 3.36 (s, 8H, -OC(=O)CH2N<), 3.19 (s, 8H, Ring-CH2-), 2.85 - 2.43 (m, 32H; 16H, Ring-H; 16H, >NCH2CH2-), 2.18 - 2.10 (m, 16H, -CH2CH2C(=O)O-), 1.84 - 1.76 (m, 16H, -C(=O)OCH2CH2CH2-), 1.64 - 1.56 (m, 16H, -OC(=O)CH2CH2-), 1.52 - 1.21 (m, 160H, -CH2CH2CH2-, -CH2CH3), 0.88 (t, 24H, -CH2CH3). MS(ESI): m / z=2954.3 ([M+H] + )。 Example 45: Cationic Lipid (E45-1) The preparation process is as follows: S43-3 (0.97 g, 1.2 mmol) and DIPEA (0.93 g, 7.2 mmol) were successively added to the methanol solution of S7-1 (2.65 g, 14.4 mmol), and the reaction solution was placed in a reflux device (90 °C) and continuously stirred for reaction for 24 h. After the reaction was completed, the reaction solution was concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E45-1 (1.87 g). 1 1H NMR (400 MHz, CDCl3) δ: 4.25 - 4.09 (m, 16H, -C(=O)OCH2CH2OC(=O)-), 3.52 - 3.41 (m, 8H, -CH(OH)-), 3.33 (s, 8H, -OC(=O)CH2N<), 3.20 (s, 8H, Ring-CH2-), 2.84 - 2.43 (m, 32H; 16H, Ring-H; 16H, >CHCH2N<), 1.46 - 1.23 (m, 144H, -CH2CH2CH2-, -CH2CH3), 0.87 (t, 24H, -CH2CH3). MS(ESI): m / z=2281.8 ([M+H] + )。 Example 46: Cationic Lipid (E46-1) The preparation process is as follows: Under nitrogen protection, compound S43-3 (0.41 g, 0.5 mmol) was dissolved in acetonitrile (30 mL). Under slow stirring, S16-3 (2.10 g, 6.0 mmol) and DIPEA (0.65 g, 5.0 mmol) were added successively, and the reaction was stirred at room temperature for about 20 h. After the reaction was completed, the reaction solution was concentrated, then dissolved in dichloromethane, and extracted successively with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution. The organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. The crude product was purified by column chromatography to obtain cationic lipid E46-1 (1.24 g). 1 H NMR (400 MHz, CDCl3) δ: 4.26 - 4.09 (m, 32H; 16H, -C(=O)OCH2CH2OC(=O)-; 16H, -NHC(=O)OCH2-), 3.34 (s, 8H, -OC(=O)CH2N<), 3.21 (s, 8H, Ring-CH2-), 3.15 (t, 16H, -CH2NHC(=O)O-), 2.83 - 2.42 (m, 32H; 16H, Ring-H; 16H, >NCH2CH2-), 1.61 - 1.22 (m, 192H, -CH2CH2CH2-, -CH2CH3), 0.88 (t, 24H, -CH2CH3). MS(ESI): m / z=3074.4 ([M+H] + )。 Example 47: Preparation of LNP-mRNA Pharmaceutical Composition and Testing of Its Physicochemical Properties Example 47.1: 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 steroid 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 cationic lipid, DSPC, cholesterol, and polyethylene glycolylated lipid stock solutions. Dissolve the cationic lipid, DSPC, cholesterol, and polyethylene glycolylated lipid in ethanol to obtain an ethanol-phase solution (the cationic lipids used in the control groups LCT-1, LCT-2, LCT-3, and LCT-4 are the cationic lipids of the prior art, and the cationic lipids of the experimental groups L-1 to L-50 are all nitrogen-containing heterocyclic cationic lipids in Examples 1-46 of the present invention; among them, the lipid molar ratios used in LCT-1, LCT-2, LCT-3, and L-1 to L-48 are 35:16:46.5:2.5, and the lipid molar ratios used in LCT-4, L-49 to L-50 are 50:10:38:1.5). Among them, the cationic lipid used in LCT-1 is C-1, which is prepared by referring to the method disclosed in the patent document CN115010681A. The cationic lipid used in LCT-2 is C-2, which is prepared by referring to the method disclosed in the patent document US20220040308A1. The cationic lipid used in LCT-3 is 244cis, which is prepared by referring to the method disclosed in "Kim, Minjeong, et al. Novel piperazine-based ionizable lipid nanoparticles allow the repeated dose of mRNA to fibrotic lungs with improved potency and safety. Bioengineering & Translational Medicine 8.6 (2023): e10556." The structures of C-1, C-2, and 244cis are as follows: C-1: C-2: 244cis: Step b: Add Fluc-mRNA to a 10-50 mM citrate buffer solution (pH = 4) to obtain an aqueous-phase solution. Step c: Mix the ethanol-phase solution and the aqueous-phase 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 for standby. Example 47.2: Physicochemical property test of LNP-mRNA pharmaceutical composition Determination of encapsulation efficiency: The encapsulation efficiency of the LNP-mRNA composition was determined using the Quant-it Ribogreen RNA quantification kit. The results showed that the lipid compositions (L-1 to L-50) of the present invention had a high encapsulation efficiency for nucleic acid drugs (mRNA), all within the range of 80% - 96%, and most of the encapsulation efficiencies were within the range of 90% - 96%. The results indicated that the cationic lipids containing nitrogen heterocycles in each experimental group could well encapsulate mRNA, showing an encapsulation efficiency equivalent to or better than that of C-1, C-2, and 244cis. There were 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 was determined by dynamic light scattering (DLS). The measured LNP-mRNA had a high size uniformity, and its PDI was less than 0.3. The particle size of LNP-mRNA prepared from the lipid composition of the present application was 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 48: Biological activity test of the LNP-mRNA pharmaceutical composition (1) Serum stability evaluation The LNP-mRNA pharmaceutical composition 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 change in the particle size of LNP-mRNA, and the serum stability of the LNP-mRNA pharmaceutical composition formulation was analyzed by testing the change in its particle size. The experimental results showed that within 7 days, the change in particle size of both the control group and the experimental groups was less than 10%, and the change in particle size of all biological experimental groups was less than 5%, indicating that the LNP-mRNA pharmaceutical composition formulation prepared from the cationic lipids of the present invention had good serum stability. (2) Study on cytotoxicity (biocompatibility) Prepare DMEM high-glucose complete medium containing 10% FBS. Respectively prepare working solutions of 0.1, 0.15, 0.2, 0.25, and 0.3 μg / 100 μL of the samples (L-1 to L-50 and L-CT1 to L-CT4) using the complete medium, and store for later use. Take 293T cells in the logarithmic growth phase and inoculate them into 96-well plates at 7×10³ cells / well and 100 μL / well. Both the control group and the experimental group are set with 6 replicates. After incubating in a 5% CO₂, 37 °C constant temperature incubator for 24 h, retain the original medium, add 100 μL / well of the complete medium to the control group, and add 100 μL / well of the working solution to the sample group. After continuing to incubate for 24 h, add 100 μL / well of the medium containing 10% CCK-8 and culture in a 5% CO₂, 37 °C constant temperature incubator for 2 h. Use an enzyme-linked immunosorbent assay (ELISA) reader to detect the absorbance value at 450 nm. 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 show that the LNP-mRNA pharmaceutical composition prepared with the cationic lipid of the present invention does not produce obvious cytotoxicity at 5 concentration gradients, and the cell survival rate is greater than 95%. Specifically, for example, the results of the experimental group L-15 are shown in Figure 8. (3) Evaluation of in vitro transfection effect To investigate the mRNA transfection efficiency of each group of LNP-mRNA pharmaceutical compositions prepared in Example 47.1 of the present invention at the cellular level, Luciferase bioluminescence was used for testing. The LNP-mRNA pharmaceutical composition was dissolved in the culture medium to prepare the required dose. Using 293T cells as the cell model, with an inoculation density of 6000 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 h of transfection, the old culture medium was removed and replaced with a new culture medium containing the substrate D-luciferin sodium (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. Among them, 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 rates of the LNPs prepared therefrom are all superior to those of L-CT1, L-CT2, and L-CT3 groups prepared from nitrogen-containing heterocyclic cationic lipids in the prior art. The relative fluorescence values of the experimental groups L-1, L-3, L-15, L-16, L-19, L-26, L-27, L-28, L-30, L-32, and L-36 are relatively high. At the same time, there are differences in the fluorescence intensity of each experimental group, which may be due to the following differences in each cationic lipid: the type and / or number of biodegradable linkers, and / or the type of hydrophobic hydrocarbon tail chain, and / or the saturation of the hydrophobic hydrocarbon tail chain, and / or the carbon chain length between the linker and the tertiary amine, and / or the number of ionizable tertiary amines. Specifically, compared with E8-1 (L-10), E9-1 (L-11), and E35-1 (L-37), E8-1 and E9-1 with a linker in the hydrophobic hydrocarbon tail chain have higher transfection rates, and the transfection rate of E8-1 with an ester bond as the linker is higher than that of E9-1 with an amide bond as the linker. This may be because the biodegradable ester bond can avoid the endosomal accumulation of LNP-mRNA and promote the endosomal escape of LNP-mRNA, and the mRNA is released into the cytoplasm to exert its efficacy; compared with E1-1 (L-1), E17-1 (L-19), and E6-1 (L-6), E1-1 and E17-1 with unsaturated hydrophobic hydrocarbon tail chains have higher transfection rates, which may be because the unsaturated hydrocarbon chain can increase the membrane fluidity and improve cell uptake.Compared with E2-1 (L-2), E3-1 (L-3), and E31-1 (L-33), which also contain unsaturated hydrocarbon chains, the transfection efficiency order is E3-1 > E2-1 > E31-1, further indicating that introducing an ester bond in the hydrophobic hydrocarbon tail chain shows better delivery effects and faster in vivo liver and plasma elimination. In this application, the cationic lipids used in groups L-41 to L-48 are nitrogen-containing heterocyclic nuclei with more tertiary amines than piperazine rings, which can effectively transfect cells with nucleic acids. Although they contain a relatively large number of tertiary amines, they do not have the optimal transfection efficiency. This may be because the molar ratios used in this application are more suitable for cationic lipids containing piperazine rings, and the formulations of cationic lipids with more tertiary amines need to be further optimized. In addition, LNP-mRNAs prepared with different molar ratios also showed certain differences. When using cationic lipid C-1 to prepare LNP-mRNA with a molar ratio of 35:16:46.5:2.5 (L-CT1), its transfection efficiency was only 75% of that of LNP-mRNA with a molar ratio of 50:10:38:1.5 (L-CT4). This may be because only the piperazine ring in C-1 provides effective ionizable tertiary amines, and it only contains two linear hydrophobic hydrocarbon tail chains. This structure is not conducive to forming a conical geometry, thus resulting in a lower transfection efficiency. Comparing L-15 and L-49, L-27 and L-50, the transfection effects of the two groups of LNP-mRNAs prepared with cationic lipids E13-1 and E25-1 are comparable, or the group with a molar ratio of 35:16:46.5:2.5 is slightly better, indicating that the cationic lipids of the present invention can also exhibit excellent transfection effects at a lower molar ratio, which can greatly reduce the dosage of cationic lipids. Table 2: Results of cell transfection tests (5) Evaluation of in vivo transfection effect Lipid nanoparticles L-15 were delivered to 6-8-week-old female BALB / c mice at a dose of 10 μg / mouse via tail vein injection, 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 9) showed that the lipid nucleic acid drug composition prepared with the cationic lipids of the present invention can achieve efficient in vivo delivery of nucleic acid drugs, and the LNP-mRNA drug composition delivered into the body is mainly distributed in the liver and spleen. The above are only embodiments of the present invention, and do not limit the patent scope of the present invention accordingly. Any equivalent structure or equivalent process transformation made by using the content of the specification of the present invention, or directly or indirectly applied in other related technical fields, is 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 unnecessary experiments, the present invention can be implemented within a relatively wide range under equivalent parameters, concentrations and conditions. Although specific embodiments of the present invention are given, 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 cover any changes, uses or improvements to the present invention, including those that depart from the scope disclosed in this application and are made by using conventional techniques known in the art.

Claims

1. A cationic lipid, characterized in that, The structure is as shown in the general formula (1-A): 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, where 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-, -NH-, -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, where R c is independently H or C 1-12 alkyl each time it appears; p is an integer from 1 to 4; Each occurrence of B1 and B2 is independently a linking bond 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 -(CH2) tn L a (CH2) tn -; said L a is selected from any one of -OC(=O)-, -C(=O)O-, -OC(=O)O-, -CH(OH)-, -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-; wherein, s is 1, 2, 3 or 4; each occurrence of tn is independently an integer from 0 to 12; 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; c is 2, 3 or 4.

2. The cationic lipid according to claim 1, wherein The structure of the cationic lipid is shown in the general formula (1-A-1): wherein, tm is independently an integer from 1 to 5 each time it appears; Z is -O- or -NH-.

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

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 C 2-10 alkylene group; Case (2): One of B1 and B2 is a linking bond and the other is C 1-20 alkylene; Case (3): Both B1 and B2 are linking bonds; More preferably, B1 and B2 are selected from the aforementioned Case (1) or Case (3); Among them, the aforementioned C 2-10 The alkylene group is preferably any one of ethylene group, propylene group, butylene group, pentylene group, hexylene group, heptylene group, and octylene group.

6. The cationic lipid according to claim 1, wherein Each occurrence of L1 and L2 is independently a linking bond or L a ; said L a is selected from any one of -OC(=O)-, -C(=O)O-, -OC(=O)O-, -CH(OH)-, -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-; More preferably, 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 connection key, and the other is L a ; Case (3): Both L1 and L2 are linking bonds; More preferably, L1 and L2 are each independently a linking bond, -C(=O)-, -O-, -NH-, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -CH(OH)-, -OC(=O)NH-, -NHC(=O)O-, -NHC(=O)- and -C(=O)NH-.

7. The cationic lipid according to claim 1, wherein Each occurrence of L3 and L4 is independently a linking bond, -L a -, -(CH2) tn L a -, -L a (CH2) tn -, -(CH2) tn L a (CH2) tn -, where tn is an integer from 1 to 12; preferably, L3 and L4 are each independently -(CH2) tn C(=O)-, -(CH2) tn C(=O)O-, -(CH2) tn OC(=O)-, -(CH2) tn OC(=O)O-, -(CH2) tn OC(=O)NH-, -(CH2) tn Any one of NHC(=O)O-, the right end of which is connected to B1 or B2; preferably, L3 and L4 are each independently any one of a linking bond, -CH2CH(OH)-, -(CH2)2C(=O)NH-, -C(=O)-, and -C(=O)O-; more preferably, L3 and L4 are the same and are a linking bond, -CH2CH(OH)-, or -(CH2)2C(=O)NH-.

8. The cationic lipid according to claim 1, wherein Each of R1 and R2 is independently C 5-30 a linear hydrocarbon group, C 5-30 a branched hydrocarbon group or C 5-30 a hydrocarbon group derivative, and the C 5-30 hydrocarbon group derivative is represented as Each of the linear hydrocarbon group and the branched hydrocarbon group is independently substituted or unsubstituted, and the substitution is preferably by C 1-6 an alkyl group, a halogen or a 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 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 is represented 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 straight-chain hydrocarbon group, and the other is a C 5-30 branched-chain hydrocarbon group Case (3): Each of R1 and R2 is 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 straight-chain hydrocarbon group or C 5-30 a branched-chain hydrocarbon group Another one is R1 and R2 satisfying the above conditions are further preferably each independently any one of the following structures:

10. The cationic lipid according to any one of claims 1-9, characterized in that, -L3-B1-L1-R1 and -L4-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, L1, L2, L3, L4, B1 and B2 are not linking bonds; Preferably, the structure of the cationic lipid satisfies any one of the following general formulas: More preferably, the structure of the cationic lipid satisfies any of the following general formulas: wherein, * represents the same structure as in [ ]; In all the aforementioned 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- each time they appear; more preferably, L1 and L2 are each independently -C(=O)-, -C(=O)O-, -OC(=O)-, -OC(=O)O-. The structure of the preferred cationic lipid satisfies any one of formulas (4-1) to (4-3); preferably, in formula (4-1), L3 and L4 are each independently -CH2CH(OH)-, and L1 and L2 are any one of -C(=O)O-, -OC(=O)-, -OC(=O)O-; in formula (4-3), R1 and R2 are each independently C 5-25 alkenyl or C 5-25 alkynyl.

12. The cationic lipid according to claim 1, wherein Its structure is any one 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, characterized in that, It further contains one or more of phospholipid, steroid lipid and polyethylene glycolated lipid; selected from any one of the following cases: Case (1): It further contains phospholipid; Case (2): It further contains steroid lipid; Case (3): It further contains polyethylene glycolated lipid; Case (4): It further contains phospholipid and steroid lipid; Case (5): It further contains phospholipid and polyethylene glycolated lipid; Case (6): It further contains steroid lipid and polyethylene glycolated lipid; Case (7): It further contains phospholipid, steroid lipid and polyethylene glycolated lipid; Case (8): It further contains phospholipid, steroid lipid, polyethylene glycolated lipid and another cationic lipid; Case (9): It further contains phospholipid, steroid lipid, polyethylene glycolated lipid and anionic lipid; More preferably, it further contains three lipids of phospholipid, steroid lipid and polyethylene glycolated lipid 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 hemisuccinyl-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 composition; or the structure of the polyethylene glycolated lipid is selected from any one of the following structures and their combinations: Wherein, n1 is an integer from 25 to 300, and more preferably n1 is any one of 44, 45, 46, 47, 48; 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)prop-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 (dilinoleyl) 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 composition; 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 composition.

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, it is 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, it is 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, it is 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, it is 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, 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.

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, and 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.

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.

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