Asymmetric cationic lipid containing multiple tertiary amines

Abstract

The present invention belongs to the field of drug delivery. Provided is an asymmetric cationic lipid containing multiple tertiary amines, of which the structure is shown as a general formula (1), wherein the definition of each symbol is consistent with that in the description. In the present invention, a degradable group is introduced into a proper position of the cationic lipid, and the presence of the degradable group enables an LNP-drug composition prepared from the cationic lipid to be degradable in endosomes at a proper time and to have small cytotoxicity, thereby solving the problem that in the prior art, LNP-drug compositions prepared from non-degradable lipids will accumulate in endosomes and acidify the endosomal environment, which hinders the endosomal escape of drugs (such as mRNAs) and causes that the drugs delivered into cells fail to sufficiently exert the therapeutic effects. The cationic lipid in the present invention uses a heterofunctionalized piperazine-containing small molecule as a raw material, involves a simple preparation process and a lower cost, and is more green and environmentally-friendly. An LNP-mRNA composition prepared from the cationic lipid has the advantages of low toxicity, high biocompatibility, high cell transfection, etc.

Description

An asymmetric cationic lipid containing a multi-stage tertiary amine Technical Field The present invention belongs to the field of drug delivery, and particularly relates to an asymmetric cationic lipid containing a multi-stage tertiary amine in a pharmaceutical carrier, and more particularly to an asymmetric cationic lipid branched with a piperazine ring, a lipid composition, a lipid drug composition, and a preparation and application thereof containing the cationic lipid. Background Art Nucleic acid drugs are a general term for oligoribonucleotides (RNA) or oligodeoxyribonucleotides (DNA) with different functions, which act at the gene level, including but not limited to: siRNA, miRNA, antisense nucleic acid, aptamer, DNA, messenger RNA (mRNA), etc. Among them, mRNA is a single-stranded ribonucleic acid transcribed from one strand of DNA as a template, carrying genetic information and capable of guiding protein synthesis. In recent years, due to the advantages of mRNA when used as a drug or vaccine, such as translation in the cytoplasm, simple production process, rapid synthesis, low cost, and conducive to large-scale production, mRNA has been applied to the prevention and treatment research of different types of diseases, especially in the vaccine field. mRNA has the disadvantages of easy degradation, instability, and difficulty in entering cells, and these defects can be overcome by optimizing its own chemical structure and selecting a suitable delivery system. Currently, the mRNA delivery system is one of the most critical technologies restricting the development of mRNA drugs. The mRNA delivery system mainly includes viral vectors and non-viral vectors. Viral vectors have the risk of integrating into the host genome and may produce varying degrees of humoral or cellular immune responses, so their clinical use is restricted. Non-viral vectors mainly include liposomes, lipid nanoparticles (LNP), inorganic nanoparticles, polymers, and proteins. Lipid nanoparticles are currently the most concerned and studied delivery systems. Lipid nanoparticles are usually composed of cationic lipids, neutral lipids, steroid lipids, and polyethylene glycolated lipids compounded under appropriate conditions. Among them, cationic lipids are connected to nucleic acids through electrostatic interactions, and the cationic lipid component has a significant impact on the delivery performance of lipid nanoparticles. Existing maturely applied cationic lipids include MC3, ALC-0315, SM-102, etc. However, the lipid nanoparticle delivery technology for mRNA still faces many challenges. Different research systems will have different optimal cationic lipids and / or lipid formulation ratios. Therefore, there is still a need for improved cationic lipids suitable for conventional therapeutic uses in this field. Summary of the Invention To solve the above problems, the present invention provides a piperazine ring-branched asymmetric cationic lipid and its preparation method, a lipid composition containing the cationic lipid, a lipid drug composition and its preparation containing the lipid composition, and a liposome or lipid nanoparticle containing the lipid composition, especially an LNP-nucleic acid drug composition and its preparation containing the cationic lipid, which have the advantages of high delivery efficiency, low safety and toxicity, high biocompatibility, and reduced cationic lipid dosage, and can improve the therapeutic and / or prophylactic effect of drugs. The above object of the present invention is achieved by the following technical solutions: An embodiment of the present invention provides a cationic lipid: A cationic lipid, characterized in that its structure is shown in the general formula (1): Or its salt, tautomer, stereoisomer, deuterated compound or solvate; Wherein, L d Is -(CH2) ta N<, the left end of which is connected to the piperazine ring, ta is an integer of 1-6, and a is 2; L e Is C 1-12 Alkylene or -CH2CH(OH)-(CH2) tb -, tb is an integer of 1-10, and the left end of -CH2CH(OH)-(CH2) tb - is connected to the piperazine ring; M is any one of -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -NH-, -O(CH2) s O-, -S-, -S-S-, -C(=O)S-, -SC(=O)-, -NHC(=O)-, -C(=O)NH-, -NHC(=O)NH-, -OC(=O)NH-, -NHC(=O)O-, -SC(=O)NH-, -NHC(=O)S-, -C(=S)-, -OC(=S)-, -C(=S)O-, -OC(=S)O-, -NHC(=S)-, -C(=S)NH-, -NHC(=S)NH-, -OC(=S)NH- and -NHC(=S)O-; R is Wherein, tm is an integer of 0-6; B1, B2, B3 are each independently a linking bond or C 1-20 Alkylene; L1, L2, L3 are each independently a linking bond or L c , L cSelected from -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -NH-, -O(CH2) s O-, -S-, -S-S-, -C(=O)S-, -SC(=O)-, -NHC(=O)-, -C(=O)NH-, -NHC(=O)NH-, -OC(=O)NH-, -NHC(=O)O-, -SC(=O)NH-, -NHC(=O)S-, -C(=S)-, -OC(=S)-, -C(=S)O-, -OC(=S)O-, -NHC(=S)-, -C(=S)NH-, -NHC(=S)NH-, -OC(=S)NH- and -NHC(=S)O-; each occurrence of R1, R2, R3 is independently a linear or branched C 5-30 hydrocarbyl group; when B1, B2, L1, L2 are all linking bonds, L e is -CH2CH(OH)-(CH2) tb -; s is 1, 2 or 3; R g is H or C 1-6 alkyl group. 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). 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), and the drug is selected from any one of nucleic acid drugs, gene vaccines, anti-tumor drugs, small molecule drugs, polypeptide drugs or protein drugs. The present invention also provides a preparation of a lipid drug composition, and the embodiment is as follows: A preparation of a lipid drug composition 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). Compared with the prior art, the present invention has the following beneficial effects: The present invention provides a new cationic lipid compound, which enriches the types of cationic lipid compounds and provides more optional cationic lipids for the delivery of nucleic acid drugs, gene vaccines, small molecule drugs, polypeptides and protein drugs, etc. The cationic lipid of the present invention introduces a piperazine ring structure into the hydrophilic head, contains multiple ionizable tertiary amines, which can strengthen its interaction with nucleic acids, and thus load more nucleic acids. The cationic lipid containing a piperazine ring of the present invention introduces a biodegradable group into the hydrophobic hydrocarbon tail. The presence of the biodegradable group enables the LNP-drug composition prepared therefrom to be degraded in a timely manner in vivo, solving the problem in the prior art that the LNP-drug composition prepared from non-degradable lipids accumulates in endosomes and acidifies the endosomal environment, resulting in hindered endosomal escape of drugs (such as mRNA) and the inability of the drugs delivered into cells to fully exert their effects; at the same time, the biodegradable group causes the cationic lipid to degrade into non-toxic metabolites under the action of intracellular enzymes, having the advantages of high safety and low cytotoxicity. The cationic lipid containing a piperazine ring of the present invention contains 3 ionizable tertiary amines, which are positively charged in an acidic environment and almost uncharged in a neutral environment. In an acidic buffer system, it binds to negatively charged nucleic acid drugs through electrostatic interaction. After entering the neutral environment in vivo, the lipid-nucleic acid drug composition (such as lipid nanoparticles) is electrically neutral, which can effectively avoid the adsorption of the lipid-nucleic acid drug composition by plasma proteins, thereby achieving higher delivery efficiency and safety. The cationic lipid containing a piperazine ring of the present invention uses a hetero-functionalized raw material containing a piperazine ring, and the preparation process is simple, with lower cost and more environmentally friendly. The LNP-mRNA composition prepared therefrom has effects such as low toxicity, high biocompatibility, and high cell transfection. Description of the Drawings Figure 1 is the 1 1H NMR spectrum of the cationic lipid E1-3 prepared in Example 1.3. Figure 2 is the 1 1H NMR spectrum of the cationic lipid E1-4 prepared in Example 1.4. Figure 3 is the 1 1H NMR spectrum of the cationic lipid E5-1 prepared in Example 5. Figure 4 is the 1 1H NMR spectrum of the cationic lipid E6-1 prepared in Example 6. Figure 5 is the 1 1H NMR spectrum of the cationic lipid E30-1 prepared in Example 30. Figure 6 shows the high performance liquid chromatography (HPLC) test results of the cationic lipid E1-3 prepared in Example 1.3. Figure 7 is the mass spectrum (MS) of the cationic lipid E1-3 prepared in Example 1.3. Figure 8 shows the cytotoxicity test results of the LNP-mRNA drug composition L-1-3 prepared in Example 34. Figure 9 shows the imaging results after injection of the LNP-mRNA drug composition L-1-3 prepared in Example 34 into mice. Embodiment Term Explanation In the present invention, unless otherwise specified, each term has the following meanings. In the present invention, when the structure involved has isomers, without special designation, it can be any one of the isomers. For example, for a structure with cis-trans isomers, it can be either the cis structure or the trans structure; for a structure with E / Z isomers, it can be either the E structure or the Z structure; when there is optical activity, it can be either levorotatory or dextrorotatory. In the present invention, the interpretation of a numerical range includes both the numerical range marked with a short dash (such as 1-6) and the numerical range marked with a tilde (such as 1~6). In the present invention, without special explanation, 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 1-6 represents the set composed of 1, 2, 3, 4, 5, and 6. The numerical ranges in the present invention include, but are not limited to, numerical ranges represented by integers, non-integers, percentages, and fractions, and all include both endpoints without special explanation. 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, "pharmaceutically acceptable salts" refer to salts of the compounds of the present invention that are recognized for use in animals, and more particularly in humans, including salts formed from the compounds represented by formula (1) and inorganic or organic acids. For example, see S.M. Berge et al., "Pharmaceutical Salts", J. Pharm. Sci. 1977, 66, 1-19. Among them, inorganic acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, phosphoric acid or nitric acid, etc.; organic acids such as formic acid, acetic acid, acetoacetic acid, pyruvic acid, trifluoroacetic acid, propionic acid, butyric acid, hexanoic acid, heptanoic acid, undecanoic acid, lauric acid, benzoic acid, salicylic acid, 2-(4-hydroxybenzoyl)-benzoic acid, camphoric acid, cinnamic acid, cyclopentanepropionic acid, digluconic acid, 3-hydroxy-2-naphthoic acid, nicotinic acid, pamonic acid, pectinic acid, 3-phenylpropionic acid, picric acid, pivalic acid, 2-hydroxyethanesulfonic acid, itaconic acid, aminosulfonic acid, trifluoromethanesulfonic acid, dodecylsulfuric acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, methanesulfonic acid, 2-naphthalenesulfonic acid, naphthalenedisulfonic acid, camphorsulfonic acid, citric acid, tartaric acid, stearic acid, lactic acid, oxalic acid, malonic acid, succinic acid, malic acid, adipic acid, alginic acid, maleic acid, fumaric acid, D-gluconic acid, mandelic acid, ascorbic acid, glucoheptonic acid, glycerophosphoric acid, aspartic acid, sulfosalicylic acid, etc. For example, pharmaceutically acceptable salts can be formed from HCl (or hydrochloric acid), HBr (or hydrobromic acid solution), methanesulfonic acid, sulfuric acid, tartaric acid or fumaric acid and the compounds represented by formula (1). In the present invention, "solvate" refers to a complex formed by combining a compound of formula (1) or a pharmaceutically acceptable salt thereof and a solvent (such as ethanol or water). It should be understood that any solvate of the compound of formula (1) used in the treatment of diseases or disorders, although it may provide different properties (including pharmacokinetic properties), once absorbed into the subject, the compound of formula (1) will be obtained, such that the use of the compound of formula (1) respectively encompasses the use of any solvate of the compound of formula (1). It should be further understood that the compound of formula (1) or a pharmaceutically acceptable salt thereof can be separated in the form of a solvate, and thus any such solvate is included within the scope of the present invention. For example, the compound of formula (1) or a pharmaceutically acceptable salt thereof can exist in an unsolvated form and in a solvated form formed with a pharmaceutically acceptable solvent (such as water, ethanol, etc.). In the present invention, unless otherwise specified, the terms "comprising", "including" and "containing" and similar expressions should be interpreted in an open and inclusive sense as "including but not limited to" in the present specification and claims. In the present invention, for two or more objects, "each independently preferably", when there are multiple levels of preference cases, it is not required that they are all selected from the same-level preferred groups. One can be a preference in a large range, one can be a preference in a small range, one can be the maximum range, and the other can be any preference case, or they can be selected from the same-level preferences. In the present invention, for the "divalent linking group", such as alkylene, alkylidene, arylene, amide bond, etc., without special limitation, when connecting other groups, either of the two connecting ends can be selected. For example, when using an amide bond as the divalent linking group between C-CH2CH2- and -CH2-D, it can be C-CH2CH2-C(=O)NH-CH2-D or C-CH2CH2-NHC(=O)-CH2-D. In the present invention, when the end groups of the linking group in the structural formula are prone to confusion with the substituents contained in the linking group, is used to mark the positions where other groups are connected in the linking group. For example, in the structural formula in, the is used to mark the two positions where other groups are connected in the divalent linking group. The above two structural formulas respectively represent -CH(CH2CH2CH3)2- and -CH2CH2CH(CH3)2-CH2CH2-. In the present invention, the range of the number of carbon atoms in the group is marked in subscript form at the subscript position of C, indicating the number of carbon atoms possessed by 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 the group obtained by substituting the hydrogen atoms of C 1-12 alkyl. "C 1-12 substituted alkyl" refers to the group obtained after substituting the hydrogen atoms of the alkyl and having 1 - 12 carbon atoms. Another example is that when a group can be selected from C 1-12 alkylene, it can be selected from any alkylene with the number of carbon atoms in the range indicated by the subscript, that is, it can be selected from any one of C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C 11 , C 12 alkylene. In the present invention, without special explanation, the subscripts marked in interval form all indicate that any integer within the range can be selected, and this range includes both endpoints. In the present invention, "group" can be 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 carbon atoms excluding the groups themselves. For example, for -OC(=O)CH2CH2OC(=O)- and -OC(=O)CH(CH3)CH2OC(=O)-, the carbon chain length between the two ester bonds is both 2 (which can also be referred to as C2), and for -OC(=O)CH2CH2OCH2CH2OC(=O)-, the carbon chain length between the two ester bonds is C4 (which can also be referred to as C4). In the present invention, the heteroatom is not particularly limited and includes, but is not limited to, O, S, N, P, Si, F, Cl, Br, I, B, etc. In the present invention, the heteroatom used for substitution is referred to as the "substituting atom", and any group used for substitution is referred to as the "substituent". In the present invention, "substituted" means that at least one hydrogen atom of any group (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 the 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 simultaneously substituted and hybridized. For example, a nitro phenyl group substitutes a hydrogen atom, or -CH2-CH2-CH2- is replaced by -CH2-S-CH(CH3)-. In the present invention, a "linking bond" is a connecting part that only serves as a connection and does not contain any atoms. When a certain group is defined as a linking bond, it means that this group can be absent. In the present invention, "each occurrence is independently" not only means that different groups can independently be any option in the definition, but also means that when the same group appears at different positions, it can also independently be any option in the definition. For example, -Z-L 6 In -Z-, "Z each occurrence is independently -C(=O)-, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -O-, -S-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-, -C(=O)NR c -, -NR c C(=O)NR c -, -OC(=O)NR c -, -NR c C(=O)O-, -SC(=O)NR c -, and -NR c C(=O)S- any one of them, where R c each occurrence is independently a hydrogen atom or C 1-12 alkyl", in "-Z-L 6 -Z-", the two Z groups can be the same or different. In the group "-NR c C(=O)NR c -", the two R c can be the same or different, and each is independently a hydrogen atom or C 1-12 alkyl. In the present invention, a "group" contains at least 1 atom, referring to a radical formed by a compound losing one or more atoms. Relative to a compound, the group formed after losing a part of the group is also called a residue. The valence state of the 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, according to the type of hydrocarbon group, hydrocarbons are classified into two types: aliphatic hydrocarbons and aromatic hydrocarbons. Hydrocarbons that do not contain a benzene ring or any structure of a benzene ring 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 olefins (containing double bonds), alkynes (containing triple bonds), dienes (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 cycloalkanes 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, compounds formed by substituting any carbon atom in a hydrocarbon with a heteroatom are collectively called hetero-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 n hydrogen atoms are lost, 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 explicitly stated in this specification, the hydrocarbon group is optionally substituted. In the present invention, there is no particular limitation on the source of the hydrocarbon group. 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 cycloalkanes, or from hydrocarbons or hetero-hydrocarbons, etc. From the perspective of saturation, for example, it can be derived from alkanes, olefins, alkynes, dienes, etc.; for cycloalkanes, for example, it can be derived from cycloaliphatic hydrocarbons or aromatic hydrocarbons, monocyclic hydrocarbons or polycyclic hydrocarbons; for heterocyclic hydrocarbons, for example, it can be derived from aliphatic heterocyclic hydrocarbons or aromatic heterocyclic hydrocarbons. In the present invention, "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. The aliphatic hydrocarbon group includes saturated aliphatic hydrocarbon groups and unsaturated aliphatic hydrocarbon groups. Unless otherwise explicitly stated in this specification, the aliphatic hydrocarbon group is optionally substituted. In the present invention, "alkyl group" refers to a hydrocarbon group formed from an alkane. Without specific designation, it refers to a hydrocarbon group formed by removing a hydrogen atom at any position, which can be straight-chain or branched-chain, and can be substituted or unsubstituted. Specifically, for example, propyl group refers to either n-propyl group or isopropyl group, and propylene group refers to any one of 1,3-propylene group, 1,2-propylene group, and isopropylene group. Unless otherwise specifically stated in this specification, the alkyl group is optionally substituted. In the present invention, "unsaturated hydrocarbon group" refers to a hydrocarbon group formed by removing a hydrogen atom from an unsaturated hydrocarbon. The hydrocarbon group formed by removing a hydrogen atom from an unsaturated carbon of an unsaturated hydrocarbon can be classified into alkenyl group, alkynyl group, diene group, etc. In the present invention, "alkenyl group" refers to a straight-chain or branched-chain hydrocarbon group containing at least one carbon-carbon double bond formed by removing a hydrogen atom at any position of an alkene. For example, "C 2-15 alkenyl group" means a straight-chain or branched-chain alkenyl group including 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 specifically stated in this specification, the alkenyl group is optionally substituted. In the present invention, "alkynyl group" refers to a straight-chain or branched-chain hydrocarbon group containing at least one carbon-carbon triple bond formed by removing a hydrogen atom at any position of an alkyne. For example, "C 2-15 alkynyl group" means a straight-chain or branched-chain alkynyl group including 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 specifically 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 group, ethylene group, propylene group, n-butylene group, vinylidene group, propenylene group, n-buteneylene group, propynylene group, n-butynylene group, etc. Unless otherwise specifically stated in this specification, the subhydrocarbon group is optionally substituted. In the present invention, "alkylene group", which is also a divalent alkyl group, includes an open-chain alkylene group and a divalent cycloalkyl group. The open-chain alkylene group refers to a divalent alkyl group without a cyclic structure, and the divalent cycloalkyl group refers to a divalent alkyl group with a cyclic structure. Unless otherwise specifically stated in this specification, the alkylene 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" indicating the number of repeating units (such as the ethylene oxide unit, EO unit in PEG) in the molecule. Correspondingly, the "average degree of polymerization", "number-average degree of polymerization", or "number of EO units" is used to characterize the average value and number-average value of the number of repeating units; when not specifically regulated, it refers to the number-average degree of polymerization. In the present invention, for percentages, "about" generally means ±0.5%. In the present invention, the "stable existence" and "degradability" of a group are relative concepts. For detailed examples of groups that can stably exist and degradable groups, see

[0134] -

[0145] section in CN113402405A. In the present invention, "hydroxy protecting group" includes all groups that can be used as the protecting group for a normal hydroxyl group. Hydroxy protecting groups are preferably alkanoyl groups (such as acetyl, tert-butylcarbonyl), aralkanoyl groups (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 ammonolysis with NH3 / MeOH and methanolysis catalyzed by methoxide anion; benzyl can be easily removed by palladium-catalyzed hydrogenolysis at room temperature in a neutral solution, and can also be cleaved by reduction with sodium metal 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 aqueous acetic acid at room temperature. In the present invention, "carboxyl protecting group" refers to a protecting group that can be converted into a carboxyl group through hydrolysis or the deprotection reaction of the carboxyl protecting group. Carboxyl protecting groups are preferably alkyl groups (such as methyl, ethyl, tert-butyl) or aralkyl groups (such as benzyl), more preferably tert-butyl (tBu), methyl (Me) or ethyl (Et). In the present invention, the "protected carboxyl group" refers to the group formed after the carboxyl group is protected by a suitable carboxyl protecting group, preferably methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, or 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 the combination of TFA and H2O, the combination of LiOH and MeOH, or the combination of LiOH and EtOH. The protected carboxyl group is deprotected to produce the corresponding free acid, and the deprotection is carried out in the presence of a base, and the base and the free acid formed by the deprotection form a pharmaceutically acceptable salt. In the present invention, the "amino protecting group" includes all groups that can be used as the protecting group of a normal amino group, such as aryl C 1-6 alkyl, C 1-6 alkoxy C 1-6 alkyl, C 1-6 alkoxycarbonyl, aryloxycarbonyl, C 1-6 alkylsulfonyl, arylsulfonyl, or silyl, etc. The amino protecting group is preferably Boc (tert-butoxycarbonyl), Moz (p-methoxybenzyloxycarbonyl), or Fmoc (9-fluorenylmethoxycarbonyl). The reagent for removing the amino protecting group is selected from TFA, H2O, LiOH, MeOH, EtOH, and combinations thereof, preferably the combination of TFA and H2O, the combination of LiOH and MeOH, or the combination of LiOH and EtOH. The reagent for removing the Boc protecting group is TFA or HCl / EA; preferably TFA. The deprotecting agent used for the reaction of removing the Fmoc protecting group is a solution of N,N-dimethylformamide (DMF) containing 20% piperidine. In the present invention, "cationic lipid" refers to a lipid that contains a positive charge or an ionizable lipid as a whole. 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 pH or hydrogen ion concentration it bears a charge or does not bear a charge. 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 greater 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" may also refer to a "poly-cationic" component / cationic component / compound. The cationic lipid may also refer to a cationic lipid capable of carrying a positive charge. For example, the cationic lipid contains one or more amine groups carrying a positive charge. 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 nanoparticles (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 a number of 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, a variant form refers to a structural form that can be transformed into a target reactive group through any one of chemical change processes such as oxidation, reduction, hydration, dehydration, electronic rearrangement, structural rearrangement, salt complexation and decomplexation, ionization, protonation, deprotonation, substitution, deprotection, change of 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 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, change of leaving group, etc. of a reactive group, or an inactive form after being protected. In the present invention, "micro-modification" refers to a chemical modification process that can be completed through a simple chemical reaction process. The simple chemical reaction process mainly refers to chemical reaction processes such as deprotection, salt complexation and decomplexation, ionization, protonation, deprotonation, transformation of leaving group, etc. The "micro-variant form" corresponds to "micro-modification" and refers to a structural form that can form a target reactive group after experiencing simple chemical reaction processes such as deprotection, salt complexation and decomplexation, ionization, protonation, deprotonation, transformation of leaving group, etc. The transformation of the leaving group, such as the transformation from an ester form to an acyl chloride form. In the present invention, the "N / P ratio" refers to the molar ratio of ionizable 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. 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, chain-terminating nucleosides, stem-loops, polyadenylation sequences, and / or polyadenylation signals. RNA may be a nucleotide sequence encoding a specific polypeptide and may be messenger RNA (mRNA). Translating mRNA encoding a specific polypeptide, for example, translating mRNA inside mammalian cells in vivo can produce the encoded polypeptide. RNA may be selected from any of the following: small interfering RNA (siRNA), asymmetric interfering RNA (aiRNA), microRNA (miRNA), Dicer-substrate RNA (dsRNA), short hairpin RNA (shRNA), mRNA, single-guide RNA (sgRNA), self-amplifying RNA (saran), circular RNA (circRNA), cas9 mRNA, and mixtures thereof. In the present invention, FLuc mRNA can express luciferase protein, which emits bioluminescence in the presence of luciferin substrate, so FLuc is commonly used in mammalian cell culture to measure gene expression and cell viability. In the present invention, the methods for determining the expression level of a target gene include, but are not limited to, dot blot, northern blot, in situ hybridization, ELISA, immunoprecipitation, enzymatic action, and phenotypic determination. In the present invention, "transfection" refers to the introduction of a substance (such as RNA) into a cell. Transfection can occur, for example, in vitro, ex vivo, or in vivo. In the present invention, "antigen" refers to a substance that can be recognized by the immune system, preferably by the adaptive immune system, and is capable of triggering an antigen-specific immune response, such as by forming antibodies and / or antigen-specific T cells as part of the adaptive immune response. Typically, an antigen can be or can 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 containing at least one epitope are also understood to be 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 which is suitable, within the scope of reasonable medical judgment, for contact with the tissues of humans and / or other animals without excessive toxicity, irritation, allergic response or other problems or complications commensurate with a reasonable benefit / risk ratio. Pharmaceutically acceptable carriers that can be used in the pharmaceutical compositions of the present invention include, but are not limited to, sterile liquids such as water and oils, including those of petroleum, animal, vegetable or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil, etc. When the pharmaceutical composition is administered intravenously, water is an exemplary carrier. Physiological saline and aqueous solutions of glucose and glycerol can also be used as liquid carriers, especially for injection solutions. Suitable pharmaceutical excipients include starch, glucose, lactose, sucrose, gelatin, maltose, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, 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 formulations may contain standard carriers such as pharmaceutical grade mannitol, lactose, starch, magnesium stearate, saccharin sodium, cellulose, magnesium carbonate, etc. Specifically, for example, excipients include, but are not limited to, anti-adhesion agents, antioxidants, binders, coatings, compression aids, disintegrants, dyes (pigments), demulcents, emulsifying agents, fillers (diluents), film formers or coatings, flavoring agents, fragrances, glidants (flow enhancers), lubricants, preservatives, printing inks, adsorbents, suspending or dispersing agents, sweetening agents, and water for hydration. More specifically, excipients include, but are not limited to, butylated hydroxytoluene (BHT), calcium carbonate, dicalcium hydrogen phosphate, calcium stearate, croscarmellose sodium, crospovidone, citric acid, crospovidone, cysteine, ethyl cellulose, gelatin, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, lactose, magnesium stearate, maltitol, mannitol, methionine, methyl cellulose, methylparaben, microcrystalline cellulose, polyethylene glycol, polyvinylpyrrolidone, povidone, pregelatinized starch, phenylparaben, retinyl palmitate, shellac, silica, sodium carboxymethyl cellulose, sodium citrate, sodium starch glycolate, sorbitol, starch (corn), stearic acid, sucrose, talc, titanium dioxide, vitamin A, vitamin E (α-tocopherol), vitamin C, xylitol. In the present invention, the pharmaceutical compositions can act systemically and / or locally. For this purpose, they can be administered by suitable routes, such as by injection (e.g., intravenous, intra-arterial, subcutaneous, intraperitoneal, intramuscular injection, including infusion) or transdermal administration; or by oral, buccal, nasal, transmucosal, topical, in the form of ophthalmic preparations or by inhalation. For these administration routes, the pharmaceutical compositions of the present invention can be administered in suitable dosage forms. The dosage forms include but are not limited to tablets, capsules, lozenges, pastilles, powders, sprays, creams, ointments, suppositories, gels, pastes, lotions, ointments, aqueous suspensions, injectable solutions, elixirs, syrups. 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. Detailed Description of the Invention 1. Cationic Lipids One embodiment of the present invention: A cationic lipid, characterized in that its structure is shown in the general formula (1): Or its salt, tautomer, stereoisomer, deuterated compound or solvate; Wherein, L d Is -(CH2) ta N<, the left end of which is connected to the piperazine ring, ta is an integer from 1 to 6, and a is 2; L e Is C 1-12 Alkylene or -CH2CH(OH)-(CH2) tb -, tb is an integer from 1 to 10, and the left end of -CH2CH(OH)-(CH2) tb - is connected to the piperazine ring; M is -OC(=O)-, -C(=O)O-, -OC(=O)O-, -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-; R is wherein tm is an integer from 0 to 6; each occurrence of B1, B2, B3 is independently a linking bond or C 1-20 alkylene; each occurrence of L1, L2, L3 is independently a linking bond or L c , L c selected from -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -NH-, -O(CH2) s O-, -S-, -S-S-, -C(=O)S-, -SC(=O)-, -NHC(=O)-, -C(=O)NH-, -NHC(=O)NH-, -OC(=O)NH-, -NHC(=O)O-, -SC(=O)NH-, -NHC(=O)S-, -C(=S)-, -OC(=S)-, -C(=S)O-, -OC(=S)O-, -NHC(=S)-, -C(=S)NH-, -NHC(=S)NH-, -OC(=S)NH- and -NHC(=S)O-; each occurrence of R1, R2, R3 is independently a linear or branched C 5-30 hydrocarbyl; when B1, B2, L1, L2 are all linking bonds, L e is -CH2CH(OH)-(CH2) tb -; s is 1, 2 or 3; R g is H or C 1-6 alkyl. 1.1. B1, B2, B3 In the present invention, B1, B2, B3 are each independently a linking bond or C 1-20 alkylene. In a specific embodiment of the present invention, B1, B2, B3 are selected from any one of the following situations: Situation (1): B1, B2, B3 are each independently C 1-20 alkylene; Situation (2): B1, B2 are linking bonds, and each occurrence of B3 is independently C 1-20 alkylene; Case (3): B1 and B2 are each independently C 1-20 an alkylene group, and B3 is a linking bond; Case (4): B1, B2, and B3 are all linking bonds; The aforementioned C 1-20 The alkylene group is preferably C 1-10 an alkylene group, more preferably any one of methylene, ethylene, propylene, butylene, pentylene, hexylene, and heptylene. 1.2. L1, L2, L3 In the present invention, each occurrence of L1, L2, and L3 is independently a linking bond or L c , where the L c is selected from any one of -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -NH-, -O(CH2) s O-, -S-, -S-S-, -C(=O)S-, -SC(=O)-, -NHC(=O)-, -C(=O)NH-, -NHC(=O)NH-, -OC(=O)NH-, -NHC(=O)O-, -SC(=O)NH-, -NHC(=O)S-, -C(=S)-, -OC(=S)-, -C(=S)O-, -OC(=S)O-, -NHC(=S)-, -C(=S)NH-, -NHC(=S)NH-, -OC(=S)NH-, and -NHC(=S)O-. In a specific embodiment of the present invention, L1, L2, and L3 are any one of the following cases: Case (1): L1, L2, and L3 are each independently L c ; Case (2): Optionally one of L1, L2, and L3 is a linking bond, and the other two are each independently L c ; preferably L3 is a linking bond, and L1 and L2 are each independently L c ; Case (3): Optionally two of L1, L2, and L3 are linking bonds, and the other one is L c ; preferably L1 and L2 are linking bonds, and L3 is L c ; Case (4): L1, L2, and L3 are all linking bonds; More preferably, L1, L2, and L3 are any one of the following cases: Case (a): L1, L2, and L3 are each independently any one of -OC(=O)-, -C(=O)O-, -C(=O)NH-, -NHC(=O)-, -OC(=O)O-, -NHC(=O)O-, -OC(=O)NH-; Case (b): L3 is a linking group, and each of L1 and L2 is independently any one of -OC(=O)-, -C(=O)O-, -C(=O)NH-, -NHC(=O)-, -OC(=O)O-, -NHC(=O)O-, -OC(=O)NH-; Case (c): L1 and L2 are linking groups, and L3 is selected from any one of -OC(=O)-, -C(=O)O-, -C(=O)NH-, -NHC(=O)-, -OC(=O)O-, -NHC(=O)O-, -OC(=O)NH-. 1.3. R1, R2, R3 In the present invention, each of R1, R2, and R3 is independently a linear or branched C 5-30 hydrocarbon group, and the hydrocarbon group is preferably an alkyl group, an alkenyl group or an alkynyl group. In a specific embodiment of the present invention, the linear C 5-30 hydrocarbon group is any one of a straight-chain alkyl group, a straight-chain alkenyl group, and a straight-chain alkynyl group; preferably each is independently a straight-chain alkyl group, a straight-chain alkenyl group, and a straight-chain alkynyl group; the linear C 5-30 hydrocarbon group is more preferably any one of the following structures: 5-30 5-30 5-25 5-25 2-25 5-30 5-30 5-30 5-30 5-30 e f In a specific embodiment of the present invention, the branched C 5-30 hydrocarbon group is a branched-chain C 5-30 alkyl group, a branched-chain C 5-30 alkenyl group or a branched-chain C 5-30 alkynyl group, and is independently represented as wherein tn is an integer from 0 to 12; R e , R f are each independently any one of a C 1-15 alkyl group, a C 2-15 alkenyl group and a C 2-15 alkynyl group, preferably R e , R f are each independently selected from any one of butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, pentenyl, hexenyl, heptenyl, octenyl, nonenyl, decenyl; the branched C 5-30 hydrocarbon group is most preferably any one of the following structures: In a specific embodiment of the present invention, R1, R2, and R3 are selected from any one of the following cases: Case (1): R1, R2, and R3 are all linear C 5-30 hydrocarbyl groups; Case (2): R1, R2, and R3 are all branched C 5-30 hydrocarbyl groups; Case (3): Any one of R1, R2, and R3 is a linear C 5-30 hydrocarbyl group, and the other two are branched C 5-30 hydrocarbyl groups; Case (4): Two of R1, R2, and R3 selected at random are linear C 5-30 hydrocarbyl groups, and the other one is a branched C 5-30 hydrocarbyl group; Preferably, R1, R2, and R3 are all linear C 5-30 hydrocarbyl groups. 1.4.R In a specific embodiment of the present invention, R is selected from any one of the following structures: 1.5. -B3-L3-R3 fragment In a specific embodiment of the present invention, the -B3-L3-R3 fragment is independently selected from any one of the following structures: 1.6. Examples of structural general formulas In a specific embodiment of the present invention, the structure of the cationic lipid satisfies any one of the following general formulas: Wherein, in general formula (1-A), L1 and L2 are divalent linking groups; wherein, M is -OC(=O)- or -C(=O)O-; the definitions of the other symbols are the same as those in formula (1). 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, in the aforementioned general formulas (1-1)-(1-10), B1 and B2 are the same, being a linking bond or C 1-12 alkylene; L1 and L2 are the same, being any one of -O-, -OC(=O)-, -C(=O)O-, -NHC(=O)-, -C(=O)NH-, -OC(=O)O-; in general formulas (1-1)-(1-20), R1 and R2 are the same, being linear C 5-30 hydrocarbyl groups; R3 is linear C 5-30 hydrocarbyl groups. 1.7. Examples of specific structures In one embodiment of the present invention, the structure of the cationic lipid is preferably selected from 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. In a specific embodiment of the present invention, the preparation process of the cationic lipid shown in formula (1) is as follows: The intermediates / raw materials involved in the preparation process of the present invention include but are not limited to PIP0, IM-N, IM-C, PIP-N, and PIP-C. In the preparation process of the present invention, the initial raw material PIP0 containing a piperazine ring may be involved. PIP0 contains the same or different functional groups F q and F0, and the structure is represented as wherein, F q is H, protected or unprotected -OH, -COOH, and F0 is protected or unprotected -NH2. The definitions of other symbols are the same as those described in general formula (1). In the present invention, PIP0 is selected from any one of the following structures: In the preparation process of the present invention, the small molecule intermediate IM-N containing a reactive group and a hydrophobic tail chain may be involved. The structure is represented as F B -B3-L3-R3, wherein, F B is a reactive group capable of reacting with F0, preferably -OH, -COOH, -F, -Cl, -Br, -CHO, -CH=CH-, and the definitions of other symbols are the same as those described in general formula (1). IM-N can be obtained by purchase or prepared by any suitable chemical reaction. The any suitable chemical reaction includes single-step or multi-step reactions such as simple esterification, amidation, alkylation, addition, or substitution. For example, in Example 8, S8-1 and S8-2 A small molecule intermediate IM-N is obtained through a substitution reaction In the present invention, the structure of the aforementioned IM-N is preferably F B -B3-L3-R3, F B -L3-R3, F B Any one of -R3. Specifically, IM-N is selected from any one of the following structures: The preparation process of the present invention may involve an intermediate IM-C containing a reactive group and a hydrophobic tail chain with carbon branching, and the structure can be represented as Or Wherein, F2 or F N Is a reactive group capable of reacting with F in PIP0 q F2 is preferably protected or unprotected -OH, -COOH, and F N Is preferably -Br, -CHO, -CH=CH-, When B1, B2, L1, and L2 are all linking bonds, F N Is The definitions of the other symbols are the same as those described in the general formula (1). IM-C can be obtained through single-step or multi-step reactions such as simple esterification, amidation, alkylation, addition, or substitution. For example, in Example 5, S5-1 And S5-2 An IM-C intermediate can be obtained through an esterification reaction followed by deprotection In the present invention, the structure of the aforementioned IM-C is preferably Any one of them. Specifically, PIP-C is selected from any one of the following structures: The preparation process of the present invention may involve an intermediate PIP-N containing a piperazine ring, a reactive group, and a hydrophobic tail chain with nitrogen branching, and the structure can be represented as Wherein, F CThe reactive groups capable of reacting with F2 of IM-C are preferably -OH and -COOH; the definitions of the other symbols are the same as those described in the general formula (1). PIP-N can be obtained by a one-step or multi-step reaction of PIP0 with IM-N. For example, in Example 1, S1-1 and S1-2 The PIP-N intermediate can be obtained by an addition reaction followed by deprotection In the present invention, the structure of the aforementioned PIP-N is preferably any one of them. Specifically, PIP-N is selected from any one of the following structures: In the preparation process of the present invention, the intermediate PIP-C containing a piperazine ring, a primary amino group, and a hydrophobic tail chain with carbon branching may be involved, and the structure is represented as The definitions of the other symbols are the same as those described in the general formula (1). PIP-C can be obtained by reacting the intermediate IM-C with the starting material PIP0. For example, in Example 30, the intermediate IM-C and PIP0 The intermediate PIP-C is obtained by an esterification reaction In the present invention, the structure of PIP-C is any one of them. Specifically, PIP-C is selected from any one of the following structures: In the present invention, the preparation of the cationic lipid can be achieved by reacting any one of the aforementioned IM-N with any one of PIP0 to obtain PIP-N, and then reacting PIP-N with IM-C; or by reacting any one of the aforementioned IM-C with any one of PIP0 to obtain PIP-C, and then reacting PIP-C with IM-N. 2.2. Description of relevant raw materials and / or steps in 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'-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 perborate, perbenzoic acid, benzoyl peroxide, nickel peroxide, hydrogen peroxide, cumene hydroperoxide, tert-butyl hydroperoxide, peracetic acid, m-chloroperbenzoic acid, N-chlorosuccinimide, pyridinium chlorochromate, palladium(II) chloride-copper(II) chloride, urea hydrogen peroxide complex, triphenylmethyl tetrafluoroborate, tributyltin oxide, cobalt(III) fluoride, vanadyl trifluoride, chromium(III) oxide, manganese(III) acetate, TEMPO, ammonium cerium(IV) nitrate, bromine, N-oxidopyridine, silver oxide, O-ethyl peroxycarbonate, manganese(III) acetylacetonate, vanadyl acetylacetonate, aluminum isopropoxide, potassium peroxymonosulfate, dichloroiodobenzene, etc., or a combination of one or more of them. More preferred are a combination of one or more of oxygen, sodium hypochlorite, hydrogen peroxide, dichloroiodobenzene, potassium peroxymonosulfate, etc. In the present invention, the reducing agent used in the reaction is not particularly limited, as long as it can reduce the Schiff base formed by ammonia and aldehyde or ketone to an amino group; preferred are sodium borohydride, sodium cyanoborohydride, lithium aluminum hydride, borane, diborane, diisobutylaluminum hydride, diisopinocampheylborane, lithium borohydride, zinc borohydride, borane-pyridine, borane-methyl sulfide, borane-tetrahydrofuran, etc., or a combination of one or more of them; more preferred is sodium cyanoborohydride. In the present invention, the solvent for the reaction can be a solvent-free or aprotic solvent. Aprotic solvents include toluene, benzene, xylene, acetonitrile, ethyl acetate, ether, methyl tert-butyl ether, tetrahydrofuran, chloroform, dichloromethane, dimethyl sulfoxide, dimethylformamide or dimethylacetamide. Preferred are tetrahydrofuran, dichloromethane, dimethyl sulfoxide, dimethylformamide. In the present invention, the base used in the reaction is an inorganic base or an organic base, preferably an organic base (such as triethylamine, pyridine, 4-dimethylaminopyridine, imidazole or diisopropylethylamine); preferably triethylamine and pyridine. 2.2.2. "Protection" and "deprotection" of 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. Moreover, when there are two or more functional groups, only the target functional group is selectively made to react, so other functional groups are protected. The protecting group not only stably protects the functional group as the object, but also needs to be easily removed as required. Therefore, in organic synthesis, it is very 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 be from a primary amine, a secondary amine, a hydrazine, an amide, etc. The amino group in the present invention is not particularly limited, including but not limited to a primary amino group, a secondary amino group, a tertiary amino group, and a quaternary ammonium ion. In the present invention, the deprotection of the protected hydroxyl group is related to the type of the hydroxyl protecting group. The type of the hydroxyl protecting group is not particularly limited. Taking the protection of the terminal hydroxyl group with a benzyl group, a silyl ether, or a tert-butyl group as an example, the corresponding deprotection methods are as follows: A: Deprotection of the benzyl protecting group The deprotection of the benzyl group can be achieved by the hydrogenation of a hydrogenation reducing agent and a hydrogen donor. The water content in this reaction system should be less than 1% for the reaction to proceed smoothly. The hydrogenation reduction catalyst is not limited. Palladium and nickel are preferred, but the carrier is not limited, but alumina or carbon is preferred, and carbon is more preferred. The amount of palladium used is 1 to 100 wt% of the compound containing the protected hydroxyl group, preferably 1 to 20 wt% of the compound containing the protected hydroxyl group. The reaction solvent is not particularly limited as long as both the raw material and the product can be dissolved. However, methanol, ethanol, ethyl acetate, tetrahydrofuran, and acetic acid are preferred; methanol is more preferred. The hydrogen donor is not particularly limited, but hydrogen, cyclohexene, 2-propanol, ammonium formate, etc. are preferred. The reaction temperature is preferably 25 to 40 °C. The reaction time is not particularly limited. The reaction time is negatively correlated with the amount of the catalyst used, and is preferably 1 to 5 hours. B: Deprotection of the silyl ether protecting group Compounds used for such hydroxyl protection include trimethylsilyl ether, triethylsilyl ether, dimethyl tert-butylsilyl ether, tert-butyldiphenylsilyl ether, etc. The deprotection of such silyl ethers is carried out by fluoride-containing compounds, preferably tetrabutylammonium fluoride, tetraethylammonium fluoride, hydrofluoric acid, potassium fluoride, more preferably tetrabutylammonium fluoride, potassium fluoride. The dosage of the fluorine-containing reagent is 5 to 20 times the molar equivalent of the protected hydroxyl group, preferably 8 to 15 times the initiator. If the dosage of fluorine is less than 5 times the molar equivalent of the protected hydroxyl group, incomplete deprotection will occur; when the dosage of the deprotection reagent is greater than 20 times the molar equivalent of the protected hydroxyl group, the excessive reagent or compound will cause trouble in purification and may be mixed into subsequent steps, thus causing side reactions. There is no particular limitation on the reaction solvent, as long as it can dissolve the reactants and products, preferably aprotic solvents, more preferably tetrahydrofuran, dichloromethane. The reaction temperature is preferably 0 to 30 °C. When the temperature is lower than 0 °C, the reaction rate is slow and the protecting group cannot be completely removed. C: Deprotection of tert-butyl protecting group The deprotection of tert-butyl is carried out under acidic conditions, and the solution pH is preferably 0 to 4. The acid is not particularly limited, but acetic acid, phosphoric acid, sulfuric acid, hydrochloric acid, nitric acid are preferred, and hydrochloric acid is more preferred. There is no particular limitation on the reaction solvent, as long as it can dissolve the reactants and products, preferably water. The reaction temperature is preferably 0 to 30 °C. 2.2.3. Alkylation reaction The alkylation reaction of the present invention is preferably a reaction based on the alkylation of hydroxyl, mercapto or amino groups, corresponding to the formation of ether bond, thioether bond, secondary amino or tertiary amino group in turn. Examples are as follows: 2.2.3.1. Alkylation of substrate alcohol with sulfonate, halide In the presence of a base, an ether intermediate is obtained by nucleophilic substitution of the substrate alcohol with a sulfonate derivative, halide. Among them, the molar equivalent of the sulfonate, halide is 1 to 50 times that of the substrate alcohol, preferably 1 to 5 times. When the molar equivalent of the sulfonate, halide is less than 1 times the molar equivalent of the substrate alcohol, the reaction substitution is incomplete and difficult to purify. When the molar equivalent of the sulfonate, halide is greater than 50 times that of the substrate alcohol, the excessive reagent causes trouble in purification and may be mixed into subsequent steps, 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 excessive sulfonate, halide, and it can be purified by anion exchange resin, osmosis, ultrafiltration, etc. Among them, the anion exchange resin is not particularly limited, as long as the target product can undergo ion exchange and adsorption on the resin, preferably an ion exchange resin of tertiary amine or quaternary ammonium salt with dextran, agarose, polyacrylate, polystyrene, polydiphenylstyrene, etc. as the backbone. The solvent for osmosis and ultrafiltration is not limited, generally water or organic solvents. Among them, the organic solvent is not particularly limited, as long as the product can be dissolved in it, preferably dichloromethane, chloroform, etc. The reaction solvent is not limited, and aprotic solvents are preferred, such as toluene, benzene, xylene, acetonitrile, ethyl acetate, tetrahydrofuran, chloroform, dichloromethane, dimethyl sulfoxide, dimethylformamide or dimethylacetamide, and dimethylformamide, dichloromethane, dimethyl sulfoxide or tetrahydrofuran are more preferred. The bases include organic bases (such as triethylamine, pyridine, 4-dimethylaminopyridine, imidazole or diisopropylethylamine) or inorganic bases (such as sodium carbonate, sodium hydroxide, sodium bicarbonate, sodium acetate, potassium carbonate or potassium hydroxide), organic bases are preferred, and triethylamine and pyridine are more preferred. The molar amount of the base is 1 to 50 times the molar equivalent of the sulfonate or halide, preferably 1 to 10 times. 2.2.3.2. Alkylation of the substrate amine with sulfonate and halide A. Alkylation of the substrate amine with sulfonate and halide In the presence of a base, an amine intermediate is obtained by nucleophilic substitution of the substrate amine with a sulfonate derivative or 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 brings trouble to purification and may be mixed into subsequent steps, resulting in an increase in side reactions in the next step and an increase in purification difficulty. The obtained product is a mixture of an amine intermediate and excess sulfonate and halide, which can be purified by column chromatography, anion exchange resin, dialysis, ultrafiltration, etc. Among them, the anion exchange resin is not particularly limited as long as the target product can undergo ion exchange and adsorption on the resin, and ion exchange resins of tertiary amines or quaternary ammonium salts with dextran, agarose, polyacrylate, polystyrene, polydiphenylethylene, etc. as the backbone are preferred. The solvents for dialysis and ultrafiltration are not limited, and generally can be water or organic solvents. The organic solvents are not particularly limited as long as the product can be dissolved in them, and dichloromethane, chloroform, etc. are preferred. The reaction solvent is not limited, and aprotic solvents are preferred, such as toluene, benzene, xylene, acetonitrile, ethyl acetate, tetrahydrofuran, chloroform, dichloromethane, dimethyl sulfoxide, dimethylformamide or dimethylacetamide, and dimethylformamide, dichloromethane, dimethyl sulfoxide or tetrahydrofuran are more preferred. The bases include organic bases (such as triethylamine, pyridine, 4-dimethylaminopyridine, imidazole or diisopropylethylamine) or inorganic bases (such as sodium carbonate, sodium hydroxide, sodium bicarbonate, sodium acetate, potassium carbonate or potassium hydroxide), organic bases are preferred, and triethylamine and pyridine are more preferred. The molar amount of the base is 1 to 50 times the molar equivalent of the sulfonate or halide, preferably 1 to 10 times, and more preferably 3 to 5 times. 2.2.3.3. Alkylation reaction of substrate amine with aldehyde derivatives After the reaction of the substrate amine with the aldehyde derivative to obtain an imine intermediate, an amine intermediate is obtained under the action of a reducing agent. Among them, the molar equivalent of the aldehyde derivative is 1 to 20 times that of the substrate amine, preferably 1 to 2 times, more preferably 1 to 1.5 times. When the molar equivalent of the aldehyde derivative is greater than 20 times that of the substrate amine, the excessive reagent brings trouble to purification, may be mixed into subsequent steps, and increases the purification difficulty. When the molar equivalent of the aldehyde derivative is less than 1 time that of the substrate amine, the reaction is incomplete and the purification difficulty increases. Among them, the reaction product can be purified by means such as cation exchange resin, osmosis, ultrafiltration, etc. The cation exchange resin has no special limitation, as long as it can exchange with quaternary ammonium cations to achieve a separation effect. The solvents for osmosis and ultrafiltration are not limited, generally water or organic solvents. The organic solvents have no special limitation, as long as the product can be dissolved in them, preferably dichloromethane, chloroform, etc. The reaction solvent is not limited, preferably organic solvents such as methanol, ethanol, water, toluene, benzene, xylene, acetonitrile, ethyl acetate, tetrahydrofuran, chloroform, dichloromethane, dimethyl sulfoxide, dimethylformamide or dimethylacetamide, etc.; more preferably water and methanol. The reducing agent has no special limitation, as long as it can reduce the imine to an amine, preferably sodium borohydride, lithium aluminum hydride, sodium cyanoborohydride, Zn / AcOH, etc., more preferably sodium cyanoborohydride. Generally, the dosage of the reducing agent is 0.5 to 50 times the amount of the aldehyde derivative substance, more preferably 1 - 10 times. 3.1. Lipid composition In the present invention, a lipid composition contains any one of the cationic lipids having the structure as shown in the general formula (1) described above. In a specific embodiment of the present invention, preferably, the lipid composition, in addition to containing the cationic lipid having the structure as shown in the general formula (1), 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; Case (9): It also contains phospholipids, steroid lipids, polyethylene glycolated lipids and anionic lipids; More preferably, it also contains three kinds of 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-diundecanoyl-sn-glycero-phosphocholine (DUPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1,2-di-O-octadecenyl-sn-glycero-3-phosphocholine (18:0Diether 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-bis-docosahexaenoyl-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-bis-docosahexaenoyl-sn-glycero-3-phosphoethanolamine, 1,2-dioleoyl-sn-glycero-3-phospho-rac-(1-glycerol) sodium salt (DOPG), dioleoyl phosphatidylserine (DOPS), dipalmitoyl phosphatidylglycerol (DPPG), palmitoyl oleoyl phosphatidylethanolamine (POPE), distearoyl-phosphatidylethanolamine (DSPE), dipalmitoyl phosphatidylethanolamine (DPPE), dimyristoyl phosphoethanolamine (DMPE), 1-stearoyl-2-oleoyl-stearoyl ethanolamine (SOPE), 1-stearoyl-2-oleoyl-phosphatidylcholine (SOPC), sphingomyelin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidic acid, palmitoyl oleoyl phosphatidylcholine, lysophosphatidylcholine and lysophosphatidylethanolamine (LPE) and their compositions. In a specific embodiment of the present invention, the steroid lipid in the lipid composition is preferably any one of cholesterol, coprosterol, sitosterol, ergosterol, campesterol, stigmasterol, brassicasterol, tomatidine, ursolic acid, α-tocopherol and their combinations. In a specific embodiment of the present invention, the polyethylene glycolated lipid in the lipid composition is preferably any one of polyethylene glycol-1,2-dimyristoyl glycerol (PEG-DMG), polyethylene glycol-distearoyl phosphatidylethanolamine (PEG-DSPE), PEG-cholesterol, polyethylene glycol-diacylglycerol (PEG-DAG), polyethylene glycol-dialkoxypropyl (PEG-DAA), specifically including polyethylene glycol 500-dipalmitoyl phosphatidylcholine, polyethylene glycol 2000-dipalmitoyl phosphatidylcholine, polyethylene glycol 500-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 their combinations. 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 their combinations: 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)propyl-1-ammonium (DOBAQ), 3,6-bis{4-[bis(2-hydroxydodecyl)amino]butyl}piperazine-2,5-dione (cKK-E12), 1,1'-((2-(4-(2-((2-(bis(2-hydroxydodecyl)amino)ethyl)(2-hydroxydodecyl)amino)ethyl)piperazin-1-yl)ethyl)azanediyl)bis(dodecan-2-ol) (C12-200), 4-(N,N-dimethylamino)butyric acid (dilinoleoyl) methyl ester (DLin-MC3-DMA), 1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine (EPC), ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate) (ALC-0315), 8-[(2-hydroxyethyl)(6-oxo-6-(undecyloxy)hexyl)amino]octanoic acid (heptadec-9-yl) ester (SM-102), and ((2-(2-hydroxyethoxy)ethyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate) (DHA-1). In a specific embodiment of the present invention, the anionic lipid in the lipid composition is selected from any one of 1,2-dioleoyl-sn-glycero-3-phosphate sodium salt (18:1PA), 1,2-dimyristoyl-sn-glycero-3-phosphate sodium salt (14:0PA), ammonium bis(monooleoylglycerol) phosphate (18:1BMP), and cardiolipin (CL). In a specific embodiment of the present invention, it contains 20 - 80% of the cationic lipid represented by formula (1), 5 - 16% of phospholipid, 25 - 55% of steroid lipid, and 0.5 - 10% of polyethylene glycolated lipid, and the percentages are the molar percentages of each lipid in the total lipid in the solution containing the solvent. In a specific embodiment of the present invention, 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. The ethanol injection method and the microfluidic method are preferred. 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. Among them, the lipid composition contains any of the aforementioned cationic lipids having a structure as shown in the general formula (1), and the drug is selected from any one of nucleic acid drugs, gene vaccines, anti-tumor drugs, small molecule drugs, polypeptide drugs, or protein drugs. In a specific embodiment of the present invention, in the lipid drug composition, the nucleic acid 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, paclitaxel, 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; preferably, lipid composition:working solution = (0.05 - 20) g:100 mL, more preferably (0.1 - 10) g:100 mL, and most preferably (0.2 - 5) g:100 mL. In a specific embodiment of the present invention, a lipid drug composition preparation contains the aforementioned lipid drug composition and a pharmaceutically acceptable diluent or excipient, 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 compounding 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 aforementioned lipid drug compositions. 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 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 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, dissolve them fully in an organic solvent, shake well, remove the organic solvent by rotary evaporation under reduced pressure to form an oil film, and dry it with a vacuum pump to remove the organic solvent; (2) Add phosphate buffer solution containing cryoprotectant, and perform ultrasonic bath to form a semi-transparent emulsion; (3) Add the emulsion to a high-pressure homogenizer for overpressure, and then add the overpressurized emulsion to a liposome extruder for membrane filtration to form liposomes; (4) Optionally, dry the liposomes in a freeze dryer to form liposome powder. In a specific embodiment of the preparation method of liposomes in the present invention, the ratio of liposomes to phosphate buffer solution containing 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 a method of microfluidics, vortex or simple mixing, and the steps are as follows: (1) Dissolve each lipid component in an organic solvent to obtain a lipid composition dissolved in the organic phase; the organic phase is preferably ethanol; (2) Add the nucleic acid drug to a buffer solution to obtain an aqueous solution; the aqueous phase is preferably citrate buffer salt or sodium acetate buffer solution; (3) Mix the organic phase solution and the aqueous solution through a microfluidic device or vortex or pipette to form a lipid nanoparticle composition, and purify it by ultrafiltration or the like 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 H NMR, electrophoresis, ultraviolet-visible spectrophotometer, FTIR, AFM, GPC, HPLC, MALDI-TOF MS and circular dichroism spectrometry and other methods. 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 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 number average degree of polymerization) of the polymer is calculated according to its molecular weight. The preparation methods of the cationic lipid, lipid composition, lipid drug composition, lipid drug composition preparation and the bioactivity test of the lipid drug composition 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 1.1: Cationic lipid (E1-1) The preparation process is as follows: Step a: Dissolve tert-butyl 4-(2-aminoethyl)piperazine-1-carboxylate (S1-1, 0.69 g, 3.0 mmol) in isopropanol. Add a sufficient amount of anhydrous potassium carbonate under stirring and stir at room temperature until the reaction solution becomes alkaline. Add dodecyl acrylate (S1-2, 2.16 g, 9.0 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 to obtain a crude product. The crude product is then dissolved in dichloromethane, add TFA to 0.1 M, react for 4 hours, adjust the pH to neutral, concentrate the reaction solution, add purified water, extract with dichloromethane, dry the extract with anhydrous magnesium sulfate, filter, concentrate the filtrate, and recrystallize to obtain the amino-exposed intermediate S1-3 (1.34 g). Step b: Under nitrogen protection, add N,N'-dicyclohexylcarbodiimide (DCC, 2.27 g, 11.0 mmol) to a round-bottom flask containing 2-hexyldecanoic acid (S1-4, 1.28 g, 5.0 mmol), 5-hexen-1-ol (S1-5, 0.6 g, 6.0 mmol) and 4-dimethylaminopyridine (DMAP, 0.15 g, 1.3 mmol) dissolved in dichloromethane (50 mL), and react at room temperature for 16 h. After the reaction is completed, remove the precipitate by filtration, concentrate the filtrate, and purify the obtained crude product by column chromatography to obtain S1-6 (1.39 g). Step c: Dissolve S1-6 (0.68 g, 2.0 mmol) in 20 mL of dichloromethane. Add m-chloroperbenzoic acid (m-CPBA, 0.52 g, 3.0 mmol) under ice bath conditions, stir for 15 min, then remove the ice bath and stir overnight. After the reaction is completed, add an excess of saturated sodium bisulfite solution and concentrate to remove dichloromethane. The residue is washed 3 times with ethyl acetate (20 mL) and saturated sodium bicarbonate solution (20 mL) and once with saturated sodium chloride solution (20 mL). The organic phase is dried with anhydrous magnesium sulfate, filtered, concentrated, and purified by column chromatography to obtain compound S1-7 (0.53 g). Step d: Add S1-3 (0.49 g, 0.8 mmol) and N,N-diisopropylethylamine (DIPEA, 0.08 g, 0.6 mmol) successively to the methanol solution of S1-7 (0.43 g, 1.2 mmol), and place the reaction solution in a reflux device (90 °C) and continue stirring for 24 h. After the reaction is completed, concentrate the reaction solution, and purify the crude product by column chromatography to obtain the cationic lipid E1-1 (0.56 g). 11H NMR (400 MHz, CDCl3) δ: 4.09 - 4.00 (m, 6H, -C(=O)OCH2-), 3.68 - 3.60 (m, 1H, -CH(OH)-), 2.80 (t, 4H, >NCH2CH2C(=O)O-), 2.69 - 2.35 (m, 19H; 4H, >NCH2CH2C(=O)O-; 1H, >CHC(=O)O-; 4H, pip-CH2CH2-; 8H, pip-H; 2H, pip-CH2CH2-), 1.63 - 1.21 (m, 70H, -CH2CH2CH2-, -CH2CH3), 0.87 (t, 12H, -CH2CH3). MS (ESI): m / z = 963.9 ([M+H] + )。 Example 1.2: Cationic Lipid (E1-2) The preparation process is as follows: Step a: Under nitrogen protection, DCC (2.27 g, 11.0 mmol) was added to a round-bottom flask containing 6-heptenoic acid (S1-9, 0.64 g, 5.0 mmol), 9-heptadecanol (S1-8, 1.54 g, 6.0 mmol) and DMAP (0.15 g, 1.3 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, and the crude product obtained was purified by column chromatography to obtain S1-10 (1.49 g). Step b: S1-10 (0.73 g, 2.0 mmol) was dissolved in 20 mL of dichloromethane, and m-CPBA (0.52 g, 3.0 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, and dichloromethane was removed by concentration. The residue was washed 3 times with ethyl acetate (20 mL) and saturated sodium bicarbonate solution (20 mL), and once with saturated sodium chloride solution (20 mL). The organic phase was dried over anhydrous magnesium sulfate, filtered, the filtrate was concentrated, and the compound S1-11 (0.57 g) was obtained by column chromatography purification. Step c: S1-3 (0.49 g, 0.8 mmol) and DIPEA (0.08 g, 0.6 mmol) were successively added to a methanol solution of S1-11 (0.46 g, 1.2 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 E1-2 (0.58 g). 11H NMR (400 MHz, CDCl3) δ: 4.90 - 4.81 (m, 1H, >CHOC(=O)-), 4.09 - 4.00 (m, 4H, -C(=O)OCH2-), 3.68 - 3.60 (m, 1H, -CH(OH)-), 2.80 (t, 4H, >NCH2CH2C(=O)O-), 2.69 - 2.35 (m, 18H; 2H, >CHOC(=O)CH2-; 4H, >NCH2CH2C(=O)O-; 4H, pip-CH2CH2-; 8H, pip-H; 2H, pip-CH2CH2-), 1.63 - 1.21 (m, 74H, -CH2CH2CH2-, -CH2CH3), 0.87 (t, 12H, -CH2CH3). MS (ESI): m / z = 991.9 ([M+H] + )。 Example 1.3: Cationic Lipid (E1-3) The preparation process is as follows: Step a: Under nitrogen protection, DCC (3.17 g, 15.4 mmol) was added to a round-bottom flask containing 6-bromohexanoic acid (S1-12, 1.37 g, 7.0 mmol), undecanol (S1-13, 1.44 g, 8.4 mmol), and DMAP (0.21 g, 1.8 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 obtained was purified by column chromatography to obtain S1-14 (1.98 g). Step b: Under nitrogen protection, compound S1-1 (0.46 g, 2.0 mmol) was dissolved in acetonitrile (20 mL), and S1-14 (1.75 g, 5.0 mmol) and DIPEA (0.52 g, 4.0 mmol) were successively added with slow stirring, and the reaction was stirred at room temperature for about 20 h. After the reaction was completed, the reaction solution was concentrated and dissolved in dichloromethane, and then extracted successively with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution. Then the organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated, and the compound S1-15 (1.05 g) was obtained by column chromatography purification. Step c: S1-15 (0.53 g, 0.8 mmol) and DIPEA (0.08 g, 0.6 mmol) were successively added to the methanol solution of S1-7 (0.43 g, 1.2 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 the cationic lipid E1-3 (0.59 g). 11H NMR (400 MHz, CDCl3) δ: 4.09 - 4.00 (m, 6H, -C(=O)OCH2-), 3.68 - 3.60 (m, 1H, -CH(OH)-), 2.71 - 2.24 (m, 23H; 4H, >NCH2CH2-; 4H, -CH2C(=O)O-; 1H, >CHC(=O)O-; 4H, pip-CH2CH2-; 8H, pip-H; 2H, pip-CH2CH2N<), 1.63 - 1.21 (m, 78H, -CH2CH2CH2-, -CH2CH3), 0.87 (t, 12H, -CH2CH3). MS (ESI): m / z = 1020.7 ([M+H] + )。 Example 1.4: Cationic Lipid (E1-4) The preparation process is as follows: S1-15 (0.53 g, 0.8 mmol) and DIPEA (0.08 g, 0.6 mmol) were successively added to the methanol solution of S1-11 (0.46 g, 1.2 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 E1-4 (0.61 g). 1 1H NMR (400 MHz, CDCl3) δ: 4.90 - 4.81 (m, 1H, >CHOC(=O)-), 4.05 (t, 4H, -C(=O)OCH2-), 3.71 - 3.61 (m, 1H, -CH(OH)-), 2.76 - 2.24 (m, 24H; 8H, pip-H; 4H, pip-CH2CH2-; 2H, pip-CH2CH2N<; 4H, >NCH2CH2-; 6H, -CH2C(=O)O-), 1.66 - 1.23 (m, 82H, -CH2CH2CH2-, -CH2CH3), 0.89 (t, 12H, -CH2CH3). MS (ESI): m / z = 1048.7 ([M+H] + )。 Example 2: Cationic Lipid (E2-1) The preparation process is as follows: Step a: At room temperature, add 4,4 - diethoxybutyronitrile (S2 - 1, 1.88 g, 12.0 mmol) and 2 - octen - 1 - ol (S2 - 2, 4.61 g, 36.0 mmol) to a round - bottom flask containing pyridinium p - toluenesulfonate (PPTS, 0.15 g, 0.6 mmol), and react the mixture at 105 °C for 20 h. After the reaction is completed, cool the reaction solution to room temperature. Purify by column chromatography to obtain compound S2 - 3 (1.62 g). Step b: Dissolve S2 - 3 (1.29 g, 4.0 mmol) in ethanol (20 mL), then add an aqueous solution of potassium hydroxide (KOH, 0.56 g, 10.0 mmol) dropwise to the mixture, and react the reaction solution at 110 °C for 24 h. After the reaction is completed, cool the reaction solution to room temperature, adjust the pH = 5 by adding 1 N HCl, extract twice with hexane (10 mL * 2), combine the organic phases, wash with water and brine, dry with anhydrous magnesium sulfate, filter, concentrate the filtrate, and purify by column chromatography to obtain the target compound S2 - 4 (1.30 g, 95%). Step c: Under nitrogen protection, add DCC (1.36 g, 6.6 mmol) to a round - bottom flask containing S2 - 4 (1.02 g, 3.0 mmol), 6 - bromo - 1 - hexanol (S2 - 5, 0.65 g, 3.6 mmol) and DMAP (0.09 g, 0.8 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 obtained crude product by column chromatography to obtain S2 - 6 (1.23 g). Step d: Under nitrogen protection, dissolve compound S1 - 3 (0.61 g, 1.0 mmol) in acetonitrile (20 mL), and successively add S2 - 6 (0.66 g, 1.3 mmol) and DIPEA (0.17 g, 1.3 mmol) with slow stirring, and stir and react at room temperature for about 20 h. After the reaction is completed, concentrate the reaction solution, dissolve it in dichloromethane, then extract successively with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution, then combine the organic phases, dry with anhydrous magnesium sulfate, filter, concentrate the filtrate, and purify by column chromatography to obtain cationic lipid E2 - 1 (0.84 g). 11H NMR (400 MHz, CDCl3) δ: 5.41 - 5.26 (m, 4H, -CH=CH-), 4.63 (t, 1H, >CH(OCH2)2-), 4.09 - 4.00 (m, 6H, -C(=O)OCH2-), 3.52 - 3.36 (m, 4H, >CH(OCH2)2-), 2.80 (t, 4H, >NCH2CH2C(=O)O-), 2.69 - 2.36 (m, 20H; 2H, >CHCH2CH2C(=O)O-; 4H, >NCH2CH2C(=O)O-; 4H, pip-CH2CH2-; 8H, pip-H; 2H, pip-CH2CH2N<), 2.11 - 1.82 (m, 10H; 2H, -CH2CH(OCH2)2-; 8H, -CH2CH2CH=CH-), 1.63 - 1.21 (m, 56H, -CH2CH2CH2-,-CH2CH3), 0.87 (t, 12H, -CH2CH3). MS (ESI): m / z=1031.9 ([M+H] + )。 Example 3: Cationic Lipid (E3-1) The preparation process is as follows: Step a: Glycerol (S3-1, 0.37 g, 4.0 mmol) was adsorbed on silica gel of the same weight by vigorous stirring for 30 minutes, then nonanoic acid (S3-2, 1.26 g, 8.0 mmol), immobilized lipase R. miehei (0.10 g) and molecular sieve (0.28 g) were successively added to the preparation, and the mixture was suspended in diethyl ether (30 mL) and stirred at room temperature for 48 h. After the reaction, the lipase and silica gel were separated by filtration, the filtrate was concentrated, and the obtained crude product was recrystallized from methanol to obtain the target compound S3-3 (1.21 g). Step b: Under nitrogen protection, DCC (0.91 g, 4.4 mmol) was added to a round-bottom flask containing 6-bromohexanoic acid (S1-12, 0.39 g, 2.0 mmol), S3-3 (0.90 g, 2.4 mmol) and DMAP (0.06 g, 0.6 mmol) dissolved in dichloromethane (20 mL), and the reaction was carried out at room temperature for 16 h. After the reaction, the precipitate was removed by filtration, the filtrate was concentrated, and the obtained crude product was purified by column chromatography to obtain S3-4 (0.93 g). Step c: Under nitrogen protection, dissolve compound S1-3 (0.61 g, 1.0 mmol) in acetonitrile (20 mL). While stirring slowly, sequentially add S3-4 (0.72 g, 1.3 mmol) and DIPEA (0.17 g, 1.3 mmol). Stir the reaction at room temperature for about 20 h. After the reaction is completed, concentrate the reaction solution, dissolve it in dichloromethane, and then extract it successively with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution. Then combine the organic phases, dry over anhydrous magnesium sulfate, filter, and concentrate the filtrate. Purify it by column chromatography to obtain cationic lipid E3-1 (0.89 g). 1 H NMR (400 MHz, CDCl3) δ: 5.37 - 5.31 (m, 1H, -C(=O)OCH<), 4.38 - 4.29 (m, 2H, >CH(CH2OC(=O))2-), 4.19 - 4.13 (m, 2H, >CH(CH2OC(=O))2-), 4.09 - 4.00 (m, 4H, -C(=O)OCH2-), 2.80 (t, 4H, >NCH2CH2C(=O)O-), 2.69 - 2.35 (m, 24H; 4H, >CHCH2OC(=O)CH2-; 2H, >CHOC(=O)CH2-; 4H, >NCH2CH2C(=O)O-; 4H, pip-CH2CH2-; 8H, pip-H; 2H, pip-CH2CH2N<), 1.63 - 1.21 (m, 70H, -CH2CH2CH2-, -CH2CH3), 0.87 (t, 12H, -CH2CH3). MS (ESI): m / z=1077.9 ([M+H] + )。 Example 4.1: Cationic Lipid (E4-1) The preparation process is as follows: Step a: Add freshly activated magnesium turnings (0.79 g, 33.1 mmol) and 2 mL of anhydrous diethyl ether to a clean round-bottom flask. Dissolve the bromide 9-bromo-1-nonene (S4-1, 5.46 g, 26.6 mmol) in anhydrous diethyl ether (80 mL) and add it to a dropping funnel. Under ice bath conditions, slowly add the bromide diethyl ether solution dropwise to the magnesium turnings. After addition is complete, allow the reaction mixture to react at 35 °C for 1 h, then cool in an ice bath. Dissolve ethyl formate (0.89 g, 12.0 mmol) in anhydrous diethyl ether (8 mL), add it to the dropping funnel, and add it to the reaction mixture with stirring. After the reaction mixture starts to reflux, quickly add the remaining ether solution of the formate. Stir the reaction mixture at room temperature for an additional 1 h. Quench the reaction by slowly adding 5 mL of acetone and ice water (15 mL). Treat the reaction mixture with aqueous H2SO4 (10% by volume, 100 mL) until the solution becomes homogeneous, and let it stand for phase separation. Extract the aqueous phase with diethyl ether (50 mL × 2), combine the organic phases, dry over anhydrous magnesium sulfate, filter, concentrate the filtrate, and purify the crude product by column chromatography to obtain compound S4-2 (3.02 g, 90%). Step b: Dissolve S4-2 (2.80 g, 10.0 mmol) in a mixed solution of dichloromethane (30 mL) and acetonitrile (30 mL), then add ruthenium(III) chloride (RuCl3, 0.37 g, 1.8 mmol). Cool the mixture to 10 °C and slowly add an aqueous solution of sodium periodate (0.22 g, 1.0 mmol) dropwise, and stir the reaction at 10 °C for 20 h. After the reaction is complete, dilute the reaction mixture with water, separate the organic and aqueous phases. Add saturated brine to the organic phase with stirring, and then slowly add 3% sodium sulfide solution for decolorization. Separate the organic and aqueous phases, dry the organic phase over anhydrous magnesium sulfate, filter, concentrate the filtrate, and obtain compound S4-3 (2.72 g). Step c: Under a nitrogen atmosphere, add tert-butyldimethylchlorosilane (1.16 g, 7.7 mmol) to a round-bottom flask containing S4-3 (2.21 g, 7.0 mmol) and imidazole (1.19 g, 17.5 mmol) dissolved in DMF (50 mL). Stir the reaction mixture at 50 °C overnight. After the reaction is complete, cool to room temperature, dilute the reaction mixture with water, extract three times with ethyl acetate, combine the organic phases and wash once with saturated brine, dry the organic phase over magnesium sulfate, filter, concentrate the filtrate, and purify by column chromatography to obtain the diacid with the hydroxyl group protected by TBS (S4-4, 2.72 g, 90%). Step d: Under nitrogen protection, DCC (1.85 g, 9.0 mmol) was added to a round-bottom flask containing 2-nonen-1-ol (S4-5, 0.71 g, 5.0 mmol), S4-4 (0.86 g, 2.0 mmol) and DMAP (0.12 g, 1.0 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, and the filtrate was concentrated. The residue was dissolved in tetrahydrofuran (10 mL), and then 10 mL of a TBAF tetrahydrofuran solution (1 M) was added, and the reaction was carried out overnight to remove the TBS protection. After the reaction was completed, the organic phase was concentrated, extracted, combined, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated to obtain the crude product of S4-6, which was further purified by column chromatography to obtain compound S4-6 (0.86 g). Step e: S4-7 (0.75 g, 4.0 mmol) was dissolved in isopropanol, and a sufficient amount of anhydrous potassium carbonate was added with stirring at room temperature until the reaction solution became alkaline. Then S1-2 (2.88 g, 12.0 mmol) was added to the reaction solution, and the reaction solution was placed in a reflux apparatus (90 °C) and stirred for reaction for 36 h. After the reaction was completed, the reaction solution was concentrated to obtain the crude product, which was purified by column chromatography to obtain compound S4-8 (1.95 g). Step f: Under nitrogen protection, DCC (0.45 g, 2.2 mmol) was added to a round-bottom flask containing S4-8 (0.67 g, 1.0 mmol), S4-6 (0.68 g, 1.2 mmol) and DMAP (0.03 g, 0.3 mmol) dissolved in dichloromethane (20 mL), and the reaction was carried out at room temperature for 16 h. After the reaction was completed, the precipitate was removed by filtration, and the filtrate was concentrated. The obtained crude product was purified by column chromatography to obtain the cationic lipid E4-1 (1.01 g). 11H NMR (400 MHz, CDCl3) δ: 5.82 - 5.71 (m, 2H, -C(=O)OCH2CH=CH-), 5.56 - 5.54 (m, 2H, -C(=O)OCH2CH=CH-), 4.93 - 4.87 (m, 1H, -C(=O)OCH<), 4.55 (t, 4H, -C(=O)OCH2CH=CH-), 4.04 (t, 4H, >N(CH2)2C(=O)OCH2-), 3.16 (s, 2H, pip-CH2C(=O)O-), 2.80 (t, 4H, >NCH2CH2C(=O)O-), 2.63 - 2.38 (m, 16H; 8H, pip-H; 2H, pip-CH2CH2-; 2H, pip-CH2CH2-; 4H, >NCH2CH2C(=O)O-), 2.18 - 2.09 (m, 4H, -OC(=O)CH2(CH2)6-), 2.06 - 1.99 (m, 4H, -CH=CHCH2CH2-), 1.64 - 1.22 (m, 80H, -CH2CH2CH2-, -CH2CH3), 0.88 (t, 12H, -CH2CH3). MS (ESI): m / z = 1214.0 ([M+H] + ). Example 4.2: Cationic Lipid (E4-2) The preparation process is as follows: Step a: Under nitrogen protection, DCC (1.85 g, 9.0 mmol) was added to a round-bottom flask containing 1-nonanol (S4-9, 0.72 g, 5.0 mmol), S4-4 (0.86 g, 2.0 mmol) and DMAP (0.12 g, 1.0 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 and the filtrate was concentrated. The residue was dissolved in tetrahydrofuran (10 mL), and then 10 mL of TBAF tetrahydrofuran solution (1 M) was added, and the reaction was carried out overnight to remove the TBS protection. After the reaction was completed, the organic phase was concentrated, extracted, combined, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated to obtain the crude product of S4-10, which was further purified by column chromatography to obtain compound S4-10 (0.88 g). Step b: Under nitrogen protection, DCC (0.45 g, 2.2 mmol) was added to a round-bottom flask containing S4-8 (0.67 g, 1.0 mmol), S4-10 (0.68 g, 1.2 mmol) and DMAP (0.03 g, 0.3 mmol) dissolved in dichloromethane (20 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 obtained was purified by column chromatography to obtain cationic lipid E4-2 (1.02 g). 1 H NMR (400 MHz, CDCl3) δ: 4.93 - 4.87 (m, 1H, -C(=O)OCH<), 4.04 (t, 8H; 4H, >N(CH2)2C(=O)OCH2-; 4H, -C(=O)OCH2(CH2)7-), 3.16 (s, 2H, pip-CH2C(=O)O-), 2.80 (t, 4H, >NCH2CH2C(=O)O-), 2.63 - 2.38 (m, 16H; 8H, pip-H; 2H, pip-CH2CH2-; 2H, pip-CH2CH2-; 4H, >NCH2CH2C(=O)O-), 2.29 (t, 4H, -(CH2)6CH2C(=O)O-), 1.84 - 1.76 (m, 8H, -C(=O)OCH2CH2-), 1.64 - 1.22 (m, 76H, -CH2CH2CH2-, -CH2CH3), 0.86 (t, 12H, -CH2CH3). MS (ESI): m / z=1218.1 ([M+H] + )。 Example 5: Cationic Lipid (E5-1) The preparation process is as follows: Step a: Under nitrogen protection, DCC (1.85 g, 9.0 mmol) was added to a round-bottom flask containing S5-2 (0.47 g, 2.0 mmol), linoleic acid (S5-1, 1.40 g, 5.0 mmol) and DMAP (0.12 g, 1.0 mmol) dissolved in dichloromethane (30 mL). The reaction was carried out at room temperature for 16 h. After the reaction was completed, the precipitate was removed by filtration, and the filtrate was concentrated. The residue was dissolved in tetrahydrofuran (10 mL), and then 10 mL of TBAF tetrahydrofuran solution (1 M) was added. The reaction was carried out overnight to remove the TBS protection. After the reaction was completed, the mixture was concentrated, extracted, and the organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated to obtain the crude product of S5-3, which was further purified by column chromatography to obtain compound S5-3 (1.00 g). Step b: Under nitrogen protection, DCC (0.45 g, 2.2 mmol) was added to a round-bottom flask containing S4-8 (0.67 g, 1.0 mmol), S5-3 (0.77 g, 1.2 mmol) and DMAP (0.03 g, 0.3 mmol) dissolved in dichloromethane (20 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 obtained was purified by column chromatography to obtain cationic lipid E5-1 (1.09 g). 1 H NMR (400 MHz, CDCl3) δ: 5.46 - 5.29 (m, 8H, -CH=CH-), 5.17 - 5.08 (m, 1H, -C(=O)OCH<), 4.19 - 4.01 (m, 8H, -C(=O)OCH2-), 3.19 (s, 2H, pip-CH2C(=O)O-), 2.87 - 2.74 (m, 8H; 4H, -CH=CHCH2CH=CH-; 4H, >NCH2CH2C(=O)O-), 2.73 - 2.35 (m, 16H; 8H, pip-H; 2H, pip-CH2CH2-; 2H, pip-CH2CH2-; 4H, >NCH2CH2C(=O)O-), 2.29 (t, 4H; >CH(CH2)2OC(=O)CH2-), 2.10 - 1.99 (m, 8H, -CH=CHCH2-), 1.97 - 1.89 (m, 4H, >CHCH2-), 1.66 - 1.22 (m, 72H, -CH2CH2CH2-, -CH2CH3), 0.88 (t, 12H, -CH2CH3). MS (ESI): m / z=1294.8 ([M+H] + )。 Example 6: Cationic lipid (E6-1) The preparation process is as follows: Step a: Under nitrogen protection, DCC (1.85 g, 9.0 mmol) was added to a round-bottom flask containing S4-4 (0.86 g, 2.0 mmol), 3-decyn-1-ol (S6-1, 0.72 g, 5.0 mmol) and DMAP (0.12 g, 1.0 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, and the filtrate was concentrated. The residue was dissolved in tetrahydrofuran (10 mL), and then 10 mL of TBAF tetrahydrofuran solution (1 M) was added, and the reaction was carried out overnight to remove the TBS protection. After the reaction was completed, it was concentrated, extracted, the organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated to obtain the crude product of S6-2, which was further purified by column chromatography to obtain compound S6-2 (0.90 g). Step b: Under nitrogen protection, DCC (0.45 g, 2.2 mmol) was added to a round-bottom flask containing S4-8 (0.67 g, 1.0 mmol), S6-2 (0.71 g, 1.2 mmol) and DMAP (0.03 g, 0.3 mmol) dissolved in dichloromethane (20 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 obtained was purified by column chromatography to obtain cationic lipid E6-1 (1.03 g). 1 1H NMR (400 MHz, CDCl3) δ: 4.93 - 4.87 (m, 1H, -C(=O)OCH<), 4.12 (t, 4H, -C≡CCH2CH2OC(=O)-), 4.04 (t, 4H, >NCH2CH2C(=O)OCH2-), 3.16 (s, 2H, pip-CH2C(=O)O-), 2.80 (t, 4H, >NCH2CH2C(=O)O-), 2.63 - 2.38 (m, 20H; 8H, pip-H; 2H, pip-CH2CH2-; 2H, pip-CH2CH2-; 4H, >NCH2CH2C(=O)O-; 4H, -C≡CCH2CH2OC(=O)-), 2.30 (t, 4H, -(CH2)4CH2C≡C-), 2.15 - 2.09 (m, 4H, -OC(=O)CH2(CH2)6-), 1.64 - 1.23 (m, 80H, -CH2CH2CH2-, -CH2CH3), 0.88 (t, 12H, -CH2CH3). MS (ESI): m / z=1239.0 ([M+H] + )。 Example 7: Cationic lipid (E7-1) The preparation process is as follows: Step a: 2-(4-(2-Aminoethyl)piperazin-1-yl)ethanol (S7-1, 0.52 g, 3.0 mmol) was dissolved in isopropanol. Under stirring, a sufficient amount of anhydrous potassium carbonate was added, and the mixture was stirred at room temperature until the reaction solution became alkaline. Then S1-2 (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 to obtain a crude product, which was purified by column chromatography to obtain compound S7-2 (1.46 g). Step b: Under ice bath conditions, dissolve S7-3 (0.60 g, 5.0 mmol) in dichloromethane solution, then add DCC (1.13 g, 5.5 mmol) and DMAP (0.31 g, 2.5 mmol). After stirring the mixture for 10 minutes, slowly add tert-butanol (t-BuOH, 0.66 g, 7.5 mmol), and stir the reaction overnight at room temperature. After the reaction is completed, filter the reaction solution through diatomaceous earth, wash it three times with ether and once with saturated brine. Combine the organic phases, dry over anhydrous magnesium sulfate, filter, concentrate the filtrate to obtain the crude product of S7-4, and purify it by column chromatography to obtain S7-4 (0.80 g, 90.8%). Step c: Under nitrogen protection, add DCC (1.85 g, 9.0 mmol) to a round-bottom flask containing S7-4 (0.35 g, 2.0 mmol), S5-1 (1.40 g, 5.0 mmol) and DMAP (0.12 g, 1.0 mmol) dissolved in dichloromethane (30 mL), and react at room temperature for 16 h. After the reaction is completed, remove the precipitate by filtration and concentrate the filtrate to obtain the crude product. In a dry and clean round-bottom flask, prepare a solution of trifluoroacetic acid / dichloromethane (1:2, v / v), and slowly add the dichloromethane solution of the above crude product dropwise under ice bath conditions, and react at room temperature for 2 h. After the reaction is completed, concentrate the reaction solution, add purified water, extract with dichloromethane, dry the extract over anhydrous magnesium sulfate, filter, concentrate the filtrate, and recrystallize to obtain compound S7-5 (1.03 g). Step d: Under nitrogen protection, add DCC (0.45 g, 2.2 mmol) to a round-bottom flask containing S7-5 (0.65 g, 1.0 mmol), S7-2 (0.78 g, 1.2 mmol) and DMAP (0.03 g, 0.3 mmol) dissolved in dichloromethane (20 mL), and react at room temperature for 16 h. After the reaction is completed, remove the precipitate by filtration and concentrate the filtrate. The obtained crude product is purified by column chromatography to obtain the cationic lipid E7-1 (1.07 g). 11H NMR (400 MHz, CDCl3) δ: 5.45 - 5.25 (m, 8H, -CH=CH-), 4.39 - 4.29 (m, 4H, >CH(CH2OC(=O)2-), 4.24 (t, 2H, pip-CH2CH2OC(=O)-), 4.05 (t, 4H, -C(=O)OCH2-), 3.02 (q, 1H, >CHC(=O)OCH2-), 2.80 (t, 4H, >NCH2CH2C(=O)O-), 2.63 - 2.38 (m, 22H; 8H, pip-H; 4H, pip-CH2CH2-; 2H, pip-CH2CH2N<; 4H, >NCH2CH2C(=O)O-; 4H, -CH=CHCH2CH=CH-), 2.29 (t, 4H, -CH2C(=O)OCH2CH<), 2.03 - 1.97 (m, 8H, -CH=CHCH2-), 1.65 - 1.23 (m, 72H, -CH2CH2CH2-, -CH2CH3), 0.86 (t, 12H, -CH2CH3). MS (ESI): m / z = 1280.1 ([M+H] + )。 Example 8: Cationic Lipid (E8-1) The preparation process is as follows: Step a: At 0 °C, add (9Z,12Z)-9,12-octadecadien-1-ol (S8-1, 2.93 g, 11.0 mmol) and triethylamine (2.59 g, 31.4 mmol) to dichloromethane (30 mL). Subsequently, slowly add a solution of acryloyl chloride (S8-2, 1.50 g, 16.5 mmol) in dichloromethane (15 mL) to the reaction system. The reaction mixture is stirred at 20 °C for 2 h. After the reaction is completed, filter to remove the precipitate. The filtrate is washed successively with water and 5% hydrochloric acid by mass, and the organic phase is dried over magnesium sulfate. Filter, concentrate the filtrate, and then purify the residue by column chromatography to obtain the target compound (9Z,12Z)-9,12-diene octadecyl acrylate (S8-3, 2.65 g). Step b: Dissolve S1-1 (0.57 g, 2.5 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 S8-3 (2.41 g, 7.5 mmol) to the reaction solution, and place the reaction solution in a reflux device (90 °C) and continue stirring for reaction for 36 h. After the reaction is completed, concentrate to remove the solvent to obtain a crude product. The crude product is then dissolved in dichloromethane, add TFA to 0.1 M, react for 4 hours, adjust the pH to neutral, concentrate the reaction solution, add purified water, extract with dichloromethane, dry the extract with anhydrous magnesium sulfate, filter, concentrate the filtrate, and recrystallize to obtain intermediate S8-4 (1.41 g). Step c: Add S8-4 (0.77 g, 1.0 mmol) and DIPEA (0.10 g, 0.8 mmol) successively to the methanol solution of S1-11 (0.57 g, 1.5 mmol), and place the reaction solution in a reflux device (90 °C) and continue stirring for reaction for 24 h. After the reaction is completed, concentrate the reaction solution, and purify the crude product by column chromatography to obtain cationic lipid E8-1 (0.84 g). 1 H NMR (400 MHz, CDCl3) δ: 5.45 - 5.25 (m, 8H, -CH=CH-), 4.90 - 4.81 (m, 1H, >CHOC(=O)-), 4.05 (t, 4H, -C(=O)OCH2-), 3.71 - 3.61 (m, 1H, -CH(OH)-), 2.84 - 2.24 (m, 28H; 8H, pip-H; 4H, pip-CH2CH2-; 2H, pip-CH2CH2-; 4H, >NCH2CH2-; 6H, -CH2C(=O)O-; 4H, -CH=CHCH2CH=CH-), 2.03 - 1.97 (m, 8H, -CH=CHCH2-), 1.84 - 1.76 (m, 4H, -C(=O)OCH2CH2-), 1.65 - 1.23 (m, 66H, -CH2CH2CH2-, -CH2CH3), 0.89 (t, 12H, -CH2CH3). MS (ESI): m / z=1152.0 ([M+H] + )。 Example 9: Cationic Lipid (E9-1) The preparation process is as follows: Under nitrogen protection, compound S8-4 (0.77 g, 1.0 mmol) was dissolved in acetonitrile (20 mL). Under slow stirring, S2-6 (0.66 g, 1.3 mmol) and DIPEA (0.17 g, 1.3 mmol) were added successively, and the mixture was stirred at room temperature for about 20 h. After the reaction was completed, the reaction solution was concentrated, dissolved in dichloromethane, and then extracted successively with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution. Then the organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. Cationic lipid E9-1 (0.99 g) was obtained by column chromatography purification. 1 H NMR (400 MHz, CDCl3) δ: 5.45 - 5.25 (m, 12H, -CH=CH-), 4.63 (t, 1H, >CH(OCH2)2-), 4.09 - 4.00 (m, 6H, -C(=O)OCH2-), 3.52 - 3.36 (m, 4H, >CH(OCH2)2-), 2.84 - 2.24 (m, 28H; 8H, pip-H; 4H, pip-CH2CH2-; 2H, pip-CH2CH2N<; 4H, >NCH2CH2-; 6H, -CH2C(=O)O-; 4H, -CH=CHCH2CH=CH-), 2.11 - 1.76 (m, 24H; 2H, -CH2CH(OCH2)2-; 16H, -CH2CH2CH=CH-; 6H, -C(=O)OCH2CH2-), 1.65 - 1.23 (m, 46H, -CH2CH2CH2-, -CH2CH3), 0.86 (t, 12H, -CH2CH3). MS (ESI): m / z=1192.0 ([M+H] + )。 Example 10: Cationic Lipid (E10-1) The preparation process is as follows: Under nitrogen protection, compound S8-4 (0.77 g, 1.0 mmol) was dissolved in acetonitrile (20 mL). Under slow stirring, S3-4 (0.72 g, 1.3 mmol) and DIPEA (0.17 g, 1.3 mmol) were added successively, and the mixture was stirred at room temperature for about 20 h. After the reaction was completed, the reaction solution was concentrated, dissolved in dichloromethane, and then extracted successively with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution. Then the organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. Cationic lipid E10-1 (1.03 g) was obtained by column chromatography purification. 11H NMR (400 MHz, CDCl3) δ: 5.45 - 5.25 (m, 9H; 8H, -CH=CH-; 1H, -C(=O)OCH<), 4.38 - 4.29 (m, 2H, >CH(CH2OC(=O))2-), 4.19 - 4.13 (m, 2H, >CH(CH2OC(=O))2-), 4.09 - 4.00 (m, 4H, -C(=O)OCH2-), 2.80 (t, 4H, >NCH2CH2C(=O)O-), 2.69 - 2.35 (m, 28H; 4H, >CHCH2OC(=O)CH2-; 2H, >CHOC(=O)CH2-; 4H, >NCH2CH2C(=O)O-; 4H, -CH=CHCH2CH=CH-; 4H, pip-CH2CH2-; 8H, pip-H; 2H, pip-CH2CH2N<), 2.03 - 1.97 (m, 8H, -CH=CHCH2-), 1.84 - 1.76 (m, 4H, -C(=O)OCH2CH2-), 1.63 - 1.21 (m, 62H, -CH2CH2CH2-, -CH2CH3), 0.87 (t, 12H, -CH2CH3). MS (ESI): m / z = 1238.0 ([M+H] + )。 Example 11: Cationic Lipid (E11-1) The preparation process is as follows: Step a: Dissolve S4-7 (0.56 g, 3.0 mmol) in isopropanol, add sufficient anhydrous potassium carbonate under stirring, and stir at room temperature until the reaction solution becomes alkaline. Then add S8-3 (2.89 g, 9.0 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 to obtain a crude product, and purify it by column chromatography to obtain compound S11-1 (1.87 g). Step b: Under nitrogen protection, add DCC (0.45 g, 2.2 mmol) to a round-bottom flask containing S11-1 (0.83 g, 1.0 mmol), S4-10 (0.68 g, 1.2 mmol), and DMAP (0.03 g, 0.3 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 obtained crude product by column chromatography to obtain cationic lipid E11-1 (1.14 g). 11H NMR (400 MHz, CDCl3) δ: 5.45 - 5.25 (m, 8H, -CH=CH-), 4.90 - 4.81 (m, 1H, >CHOC(=O)-), 4.05 (t, 8H, -C(=O)OCH2-), 3.16 (s, 2H, pip-CH2C(=O)O-), 2.84 - 2.24 (m, 28H; 8H, pip-H; 2H, pip-CH2CH2-; 2H, pip-CH2CH2-; 4H, >NCH2CH2-; 8H, -CH2C(=O)O-; 4H, -CH=CHCH2CH=CH-), 2.03 - 1.97 (m, 8H, -CH=CHCH2-), 1.84 - 1.76 (m, 8H, -C(=O)OCH2CH2-), 1.64 - 1.23 (m, 80H, -CH2CH2CH2-, -CH2CH3), 0.89 (t, 12H, -CH2CH3). MS (ESI): m / z=1378.2 ([M+H] + ). Example 12: Cationic Lipid (E12-1) The preparation process is as follows: Under nitrogen protection, DCC (0.45 g, 2.2 mmol) was added to a round-bottom flask containing S11-1 (0.83 g, 1.0 mmol), S5-3 (0.77 g, 1.2 mmol) and DMAP (0.03 g, 0.3 mmol) dissolved in dichloromethane (20 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 obtained was purified by column chromatography to obtain cationic lipid E12-1 (1.20 g). 11H NMR (400 MHz, CDCl3) δ: 5.46 - 5.29 (m, 16H, -CH=CH-), 5.17 - 5.08 (m, 1H, -C(=O)OCH<), 4.19 - 4.00 (m, 8H, -C(=O)OCH2-), 3.19 (s, 2H, pip-CH2C(=O)O-), 2.87 - 2.74 (m, 12H; 8H, -CH=CHCH2CH=CH-; 4H, >NCH2CH2C(=O)O-), 2.73 - 2.35 (m, 16H; 8H, pip-H; 2H, pip-CH2CH2-; 2H, pip-CH2CH2-; 4H, >NCH2CH2C(=O)O-), 2.29 (t, 4H; >CH(CH2)2OC(=O)CH2-), 2.10 - 1.99 (m, 16H, -CH=CHCH2-), 1.97 - 1.89 (m, 4H, >CHCH2-), 1.66 - 1.22 (m, 68H, -CH2CH2CH2-, -CH2CH3), 0.88 (t, 12H, -CH2CH3). MS (ESI): m / z=1454.2 ([M+H] + )。 Example 13: Cationic Lipid (E13-1) The preparation process is as follows: Under nitrogen protection, DCC (0.45 g, 2.2 mmol) was added to a round-bottom flask containing S11-1 (0.83 g, 1.0 mmol), S6-2 (0.71 g, 1.2 mmol) and DMAP (0.03 g, 0.3 mmol) dissolved in dichloromethane (20 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 obtained was purified by column chromatography to obtain cationic lipid E13-1 (1.16 g). 11H NMR (400 MHz, CDCl3) δ: 5.46 - 5.29 (m, 8H, -CH=CH-), 4.93 - 4.87 (m, 1H, -C(=O)OCH<), 4.12 (t, 4H, -C≡CCH2CH2OC(=O)-), 4.04 (t, 4H, >NCH2CH2C(=O)OCH2-), 3.16 (s, 2H, pip-CH2C(=O)O-), 2.87 - 2.74 (m, 8H; 4H, -CH=CHCH2CH=CH-; 4H, >NCH2CH2C(=O)O-), 2.63 - 2.38 (m, 20H; 8H, pip-H; 2H, pip-CH2CH2-; 2H, pip-CH2CH2-; 4H, >NCH2CH2C(=O)O-; 4H, -C≡CCH2CH2OC(=O)-), 2.30 (t, 4H, -(CH2)4CH2C≡C-), 2.18 - 1.99 (m, 12H; 8H, -CH=CHCH2-; 4H, -OC(=O)CH2(CH2)6-), 1.65 - 1.23 (m, 76H, -CH2CH2CH2-, -CH2CH3), 0.86 (t, 12H, -CH2CH3). MS (ESI): m / z = 1398.1 ([M+H] + )。 Example 14: Cationic Lipid (E14-1) The preparation process is as follows: Step a: Dissolve S7-1 (0.52 g, 3.0 mmol) in isopropanol, add sufficient anhydrous potassium carbonate under stirring, and stir at room temperature until the reaction solution becomes alkaline. Then add S8-3 (2.89 g, 9.0 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 to obtain a crude product, and purify it by column chromatography to obtain compound S14-1 (1.83 g). Step b: Under nitrogen protection, add DCC (0.45 g, 2.2 mmol) to a round-bottom flask containing S7-5 (0.65 g, 1.0 mmol), S14-1 (0.98 g, 1.2 mmol), and DMAP (0.03 g, 0.3 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 obtained crude product by column chromatography to obtain cationic lipid E14-1 (1.18 g). 11H NMR (400 MHz, CDCl3) δ: 5.45 - 5.25 (m, 16H, -CH=CH-), 4.39 - 4.29 (m, 4H, >CH(CH2OC(=O)2-), 4.24 (t, 2H, pip-CH2CH2OC(=O)-), 4.05 (t, 4H, -C(=O)OCH2-), 3.02 (q, 1H, >CHC(=O)OCH2-), 2.80 (t, 4H, >NCH2CH2C(=O)O-), 2.63 - 2.38 (m, 26H; 8H, pip-H; 4H, pip-CH2CH2-; 2H, pip-CH2CH2N<; 4H, >NCH2CH2C(=O)O-; 8H, -CH=CHCH2CH=CH-), 2.29 (t, 4H, -CH2C(=O)OCH2CH<), 2.03 - 1.97 (m, 16H, -CH=CHCH2-), 1.65 - 1.23 (m, 68H, -CH2CH2CH2-, -CH2CH3), 0.90 (t, 12H, -CH2CH3). MS (ESI): m / z = 1440.2 ([M+H] + ). Example 15: Cationic Lipid (E15-1) The preparation process is as follows: Step a: Dissolve S1-1 (0.57 g, 2.5 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 (S15-1, 1.79 g, 7.5 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 to obtain a crude product. The crude product is then dissolved in dichloromethane, add TFA to 0.1 M, react for 4 hours, adjust the pH to neutral, concentrate the reaction solution, add purified water, extract with dichloromethane, dry the extract with anhydrous magnesium sulfate, filter, concentrate the filtrate, and recrystallize to obtain the amino-exposed intermediate S15-2 (1.11 g). Step b: Add S15-2 (0.61 g, 1.0 mmol) and DIPEA (0.10 g, 0.8 mmol) successively to the methanol solution of S1-7 (0.53 g, 1.5 mmol), and place the reaction solution in a reflux device (90 °C) and continue stirring for 24 h. After the reaction is completed, concentrate the reaction solution, and purify the crude product by column chromatography to obtain the cationic lipid E15-1 (0.70 g). 11H NMR (400 MHz, CDCl3) δ: 4.09 - 4.00 (m, 2H, -C(=O)OCH2-), 3.68 - 3.60 (m, 1H, -CH(OH)-), 3.28 (dd, 4H, -C(=O)NHCH2-), 2.82 - 2.35 (m, 23H; 4H, >NCH2CH2C(=O)NH-; 1H, >CHC(=O)O-; 4H, pip-CH2CH2-; 8H, pip-H; 2H, pip-CH2CH2-; 4H, >NCH2CH2-), 1.63 - 1.21 (m, 70H, -CH2CH2CH2-, -CH2CH3), 0.87 (t, 12H, -CH2CH3). MS (ESI): m / z=961.9 ([M+H] + )。 Example 16: Cationic Lipid (E16-1) The preparation process is as follows: Under nitrogen protection, dissolve compound S15-2 (0.61 g, 1.0 mmol) in acetonitrile (20 mL). Add S2-6 (0.66 g, 1.3 mmol) and DIPEA (0.17 g, 1.3 mmol) successively with slow stirring, and stir the reaction at room temperature for about 20 h. After the reaction is completed, concentrate the reaction solution, dissolve it with dichloromethane, then extract it successively with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution. Then combine the organic phases, dry with anhydrous magnesium sulfate, filter, concentrate the filtrate, and purify it by column chromatography to obtain cationic lipid E16-1 (0.85 g). 1 1H NMR (400 MHz, CDCl3) δ: 5.41 - 5.26 (m, 4H, -CH=CH-), 4.63 (t, 1H, >CH(OCH2)2-), 4.09 - 4.00 (m, 2H, -C(=O)OCH2-), 3.52 - 3.36 (m, 4H, >CH(OCH2)2-), 3.28 (dd, 4H, -C(=O)NHCH2-), 2.80 - 2.35 (m, 24H; 2H, >CHCH2CH2C(=O)O-; 4H, pip-CH2CH2-; 8H, pip-H; 2H, pip-CH2CH2N<; 4H, >NCH2CH2-; 4H, >NCH2CH2C(=O)NH-), 2.11 - 1.82 (m, 10H; 2H, -CH2CH(OCH2)2-; 8H, -CH2CH2CH=CH-), 1.63 - 1.21 (m, 56H, -CH2CH2CH2-, -CH2CH3), 0.87 (t, 12H, -CH2CH3). MS (ESI): m / z=1029.9 ([M+H]+ )。 Example 17: Cationic Lipid (E17-1) The preparation process is as follows: Under nitrogen protection, compound S15-2 (0.61 g, 1.0 mmol) was dissolved in acetonitrile (20 mL). Under slow stirring, S3-4 (0.72 g, 1.3 mmol) and DIPEA (0.17 g, 1.3 mmol) were successively added, and the mixture was stirred at room temperature for about 20 h. After the reaction was completed, the reaction solution was concentrated, dissolved in dichloromethane, and then extracted successively with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution. Then the organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. The cationic lipid E17-1 (0.90 g) was obtained by column chromatography purification. 1 H NMR (400 MHz, CDCl3) δ: 5.37 - 5.31 (m, 1H, -C(=O)OCH<), 4.38 - 4.29 (m, 2H, >CH(CH2OC(=O))2-), 4.19 - 4.13 (m, 2H, >CH(CH2OC(=O))2-), 3.28 (dd, 4H, -C(=O)NHCH2-), 2.80 - 2.35 (m, 28H; 4H, >CHCH2OC(=O)CH2-; 2H, >CHOC(=O)CH2-; 4H, -CH2C(=O)NH-; 4H, >NCH2CH2-; 4H, pip-CH2CH2-; 8H, pip-H; 2H, pip-CH2CH2N<), 1.63 - 1.21 (m, 70H, -CH2CH2CH2-, -CH2CH3), 0.88 (t, 12H, -CH2CH3). MS (ESI): m / z=1075.9 ([M+H] + )。 Example 18: Cationic Lipid (E18-1) The preparation process is as follows: Step a: Dissolve S4-7 (0.75 g, 4.0 mmol) in isopropanol. With stirring, add a sufficient amount of anhydrous potassium carbonate and stir at room temperature until the reaction solution becomes alkaline. Then add S15-1 (2.87 g, 12.0 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 to obtain a crude product, and the compound S18-1 (1.94 g) is obtained by column chromatography purification. Step b: Under nitrogen protection, DCC (0.45 g, 2.2 mmol) was added to a round-bottom flask containing S18-1 (0.67 g, 1.0 mmol), S4-6 (0.68 g, 1.2 mmol) and DMAP (0.03 g, 0.3 mmol) dissolved in dichloromethane (20 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 obtained was purified by column chromatography to obtain cationic lipid E18-1 (1.01 g). 1 H NMR (400 MHz, CDCl3) δ: 5.82 - 5.71 (m, 2H, -C(=O)OCH2CH=CH-), 5.56 - 5.54 (m, 2H, -C(=O)OCH2CH=CH-), 4.93 - 4.87 (m, 1H, -C(=O)OCH<), 4.55 (t, 4H, -C(=O)OCH2CH=CH-), 3.28 (dd, 4H, -C(=O)NHCH2-), 3.16 (s, 2H, pip-CH2C(=O)O-), 2.80 - 2.38 (m, 20H; 4H, >NCH2CH2-; 8H, pip-H; 2H, pip-CH2CH2-; 2H, pip-CH2CH2-; 4H, -CH2C(=O)NH-), 2.18 - 2.09 (m, 4H, -OC(=O)CH2(CH2)6-), 2.06 - 1.99 (m, 4H, -CH=CHCH2CH2-), 1.64 - 1.22 (m, 80H, -CH2CH2CH2-, -CH2CH3), 0.87 (t, 12H, -CH2CH3). MS (ESI): m / z=1212.1 ([M+H] + )。 Example 19: Cationic lipid (E19-1) The preparation process is as follows: Step a: 5-Bromopentanol (S19-1, 1.34 g, 8.0 mmol) was dissolved in 50 mL of dichloromethane, DMAP (2.06 g, 16.0 mmol) was added, and then phenyl chloroformate p-nitro (1.77 g, 8.8 mmol) was added in batches. The reaction was stirred at room temperature for 3 h. S1-3 (1.54 g, 9.0 mmol) was added to the reaction solution, and the mixture was stirred 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, the filtrate was concentrated, and purified by column chromatography to obtain 5-bromopentyl undecyl carbonate (S19-2, 2.11 g). Step b: Under nitrogen protection, dissolve compound S1-1 (0.46 g, 2.0 mmol) in acetonitrile (30 mL). Sequentially add S19-2 (1.83 g, 5.0 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, dissolve it with dichloromethane, and then extract it successively with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution. Then combine the organic phases, dry over anhydrous magnesium sulfate, filter, and concentrate the filtrate to obtain the crude product. Dissolve the crude product in dichloromethane again, add TFA to 0.1 M, react for 4 hours, adjust the pH to neutral, concentrate the reaction solution, add purified water, extract with dichloromethane, dry the extract over anhydrous magnesium sulfate, filter, concentrate the filtrate, and recrystallize to obtain the amino-exposed intermediate S19-3 (1.11 g). Step c: Sequentially add S19-3 (0.70 g, 1.0 mmol) and DIPEA (0.10 g, 0.8 mmol) to the methanol solution of S1-11 (0.57 g, 1.5 mmol), and place the reaction solution in a reflux device (90 °C) and continue to stir the reaction for 24 h. After the reaction is completed, concentrate the reaction solution, and purify the crude product by column chromatography to obtain the cationic lipid E19-1 (0.78 g). 1 H NMR (400 MHz, CDCl3) δ: 4.90 - 4.81 (m, 1H, >CHOC(=O)-), 4.15 - 4.10 (m, 8H, -CH2OC(=O)OCH2-), 3.71 - 3.61 (m, 1H, -CH(OH)-), 2.84 - 2.24 (m, 20H; 8H, pip-H; 4H, pip-CH2CH2-; 2H, pip-CH2CH2N<; 4H, >NCH2CH2-; 2H, -CH2C(=O)O-), 1.66 - 1.23 (m, 82H, -CH2CH2CH2-, -CH2CH3), 0.89 (t, 12H, -CH2CH3). MS (ESI): m / z = 1079.9 ([M+H] + )。 Example 20: Cationic Lipid (E20-1) The preparation process is as follows: Under nitrogen protection, compound S19-3 (0.70 g, 1.0 mmol) was dissolved in acetonitrile (20 mL). Under slow stirring, S2-6 (0.66 g, 1.3 mmol) and DIPEA (0.17 g, 1.3 mmol) were added successively, and the mixture was stirred at room temperature for about 20 h. After the reaction was completed, the reaction solution was concentrated, dissolved in dichloromethane, and then extracted successively with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution. Then the organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. Cationic lipid E20-1 (0.93 g) was obtained by column chromatography purification. 1 H NMR (400 MHz, CDCl3) δ: 5.41 - 5.26 (m, 4H, -CH=CH-), 4.63 (t, 1H, >CH(OCH2)2-), 4.15 - 4.10 (m, 8H, -CH2OC(=O)OCH2-), 4.09 - 4.00 (m, 2H, -C(=O)OCH2-), 3.52 - 3.36 (m, 4H, >CH(OCH2)2-), 2.80 - 2.35 (m, 20H; 4H, >NCH2CH2-; 2H, >CHCH2CH2C(=O)O-; 4H, pip-CH2CH2-; 8H, pip-H; 2H, pip-CH2CH2N<), 2.11 - 1.82 (m, 10H; 2H, -CH2CH(OCH2)2-; 8H, -CH2CH2CH=CH-), 1.63 - 1.21 (m, 64H, -CH2CH2CH2-, -CH2CH3), 0.87 (t, 12H, -CH2CH3). MS (ESI): m / z=1119.9 ([M+H] + )。 Example 21: Cationic Lipid (E21-1) Under nitrogen protection, compound S19-3 (0.70 g, 1.0 mmol) was dissolved in acetonitrile (20 mL). Under slow stirring, S3-4 (0.72 g, 1.3 mmol) and DIPEA (0.17 g, 1.3 mmol) were added successively, and the mixture was stirred at room temperature for about 20 h. After the reaction was completed, the reaction solution was concentrated, dissolved in dichloromethane, and then extracted successively with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution. Then the organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. Cationic lipid E21-1 (0.97 g) was obtained by column chromatography purification. 11H NMR (400 MHz, CDCl3) δ: 5.37 - 5.31 (m, 1H, -C(=O)OCH<), 4.38 - 4.29 (m, 2H, >CH(CH2OC(=O))2-), 4.19 - 4.13 (m, 2H, >CH(CH2OC(=O))2-), 4.15 - 4.10 (m, 8H, -CH2OC(=O)OCH2-), 2.80 - 2.35 (m, 24H; 4H, >NCH2CH2-; 4H, >CHCH2OC(=O)CH2-; 2H, >CHOC(=O)CH2-; 4H, pip-CH2CH2-; 8H, pip-H; 2H, pip-CH2CH2N<), 1.63 - 1.21 (m, 78H, -CH2CH2CH2-, -CH2CH3), 0.87 (t, 12H, -CH2CH3). MS (ESI): m / z = 1165.9 ([M+H] + )。 Example 22: Cationic Lipid (E22-1) The preparation process is as follows: Step a: Under nitrogen protection, dissolve compound S4-7 (0.37 g, 2.0 mmol) in acetonitrile (30 mL). While stirring slowly, successively add S19-2 (1.83 g, 5.0 mmol) and DIPEA (0.52 g, 4.0 mmol), and stir the reaction at room temperature for about 20 h. After the reaction is completed, concentrate the reaction solution, dissolve it with dichloromethane, then extract it successively with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution. Then combine the organic phases, dry with anhydrous magnesium sulfate, filter, concentrate the filtrate, and purify it by column chromatography to obtain compound S22-1 (1.26 g). Step b: Under nitrogen protection, add DCC (0.45 g, 2.2 mmol) to a round-bottom flask containing S22-1 (0.76 g, 1.0 mmol), S4-6 (0.68 g, 1.2 mmol) and DMAP (0.03 g, 0.3 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 obtained crude product by column chromatography to obtain cationic lipid E22-1 (1.09 g). 11H NMR (400 MHz, CDCl3) δ: 5.82 - 5.71 (m, 2H, -C(=O)OCH2CH=CH-), 5.56 - 5.54 (m, 2H, -C(=O)OCH2CH=CH-), 4.93 - 4.87 (m, 1H, -C(=O)OCH<), 4.55 (t, 4H, -C(=O)OCH2CH=CH-), 4.15 - 4.10 (m, 8H, -CH2OC(=O)OCH2-), 3.16 (s, 2H, pip-CH2C(=O)O-), 2.80 - 2.38 (m, 16H; 4H, >NCH2CH2-; 8H, pip-H; 2H, pip-CH2CH2-; 2H, pip-CH2CH2-), 2.18 - 2.09 (m, 4H, -OC(=O)CH2(CH2)6-), 2.06 - 1.99 (m, 4H, -CH=CHCH2CH2-), 1.64 - 1.22 (m, 88H, -CH2CH2CH2-, -CH2CH3), 0.91 (t, 12H, -CH2CH3). MS (ESI): m / z = 1302.1 ([M+H] + )。 Example 23: Cationic Lipid (E23-1) The preparation process is as follows: Step a: Dissolve S1-3 (2.58 g, 15.0 mmol) in dichloromethane (80 mL), successively add triethylamine (5 mL) and N,N'-carbonyldiimidazole (CDI, 2.43 g, 15.0 mmol), and react at 50 °C for 1.5 h. Then add 5-amino-1-butanol (S23-1, 2.32 g, 22.5 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 successively with 5% citric acid (40 mL * 2) and saturated brine (40 mL), dry the organic phase over anhydrous magnesium sulfate, filter, concentrate the filtrate to obtain the crude product. Add dichloromethane (40 mL) to the crude product, stir for 10 min, filter, wash the filter cake with a small amount of dichloromethane, and concentrate to obtain the product S23-2 (2.96 g). Step b: Dissolve S23-2 (2.41 g, 8.0 mmol) in dichloromethane (100 mL), add triphenylphosphine (PPh3, 3.14 g, 12.0 mmol), and under ice bath, add carbon tetrabromide (CBr4, 3.97 g, 12.0 mmol) in batches, and react under ice bath for 20 min. 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 S23-3 (1.71 g). Step c: Under nitrogen protection, dissolve compound S4-7 (0.28 g, 1.5 mmol) in acetonitrile (20 mL). Sequentially add S23-3 (1.37 g, 3.8 mmol) and DIPEA (0.39 g, 3.0 mmol) under slow stirring, and stir the reaction at room temperature for about 20 h. After the reaction is completed, concentrate the reaction solution, dissolve it with dichloromethane, then extract it successively with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution. Then combine the organic phases, dry over anhydrous magnesium sulfate, filter, concentrate the filtrate, and purify by column chromatography to obtain compound S23-4 (0.95 g). Step d: Under nitrogen protection, add DCC (0.45 g, 2.2 mmol) to a round-bottom flask containing S23-4 (0.75 g, 1.0 mmol), S4-10 (0.68 g, 1.2 mmol), and DMAP (0.03 g, 0.3 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 obtained crude product by column chromatography to obtain cationic lipid E23-1 (1.07 g). 1 H NMR (400 MHz, CDCl3) δ: 4.93 - 4.87 (m, 1H, -C(=O)OCH<), 4.11 (t, 4H, -NHC(=O)OCH2-), 4.04 (t, 4H, -C(=O)OCH2-), 3.16 (s, 2H, pip-CH2C(=O)O-), 3.15 (t, 4H, -CH2NHC(=O)O-), 2.80 - 2.38 (m, 16H; 4H, >NCH2CH2-; 8H, pip-H; 2H, pip-CH2CH2-; 2H, pip-CH2CH2-), 2.29 (t, 4H, -(CH2)6CH2C(=O)O-), 1.84 - 1.76 (m, 4H, -C(=O)OCH2CH2-), 1.64 - 1.22 (m, 96H, -CH2CH2CH2-,-CH2CH3), 0.88 (t, 12H, -CH2CH3). MS (ESI): m / z=1304.1 ([M+H] + )。 Example 24: Cationic Lipid (E24-1) The preparation process is as follows: Under nitrogen protection, DCC (0.45 g, 2.2 mmol) was added to a round-bottom flask containing S23-4 (0.75 g, 1.0 mmol), S5-3 (0.77 g, 1.2 mmol) and DMAP (0.03 g, 0.3 mmol) dissolved in dichloromethane (20 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 obtained was purified by column chromatography to obtain cationic lipid E24-1 (1.15 g). 1 H NMR (400 MHz, CDCl3) δ: 5.46 - 5.29 (m, 8H, -CH=CH-), 5.17 - 5.08 (m, 1H, -C(=O)OCH<), 4.19 - 4.00 (m, 8H; 4H, -C(=O)OCH2-; 4H, -NHC(=O)OCH2-), 3.19 (s, 2H, pip-CH2C(=O)O-), 3.15 (t, 4H, -CH2NHC(=O)O-), 2.87 - 2.74 (m, 4H, -CH=CHCH2CH=CH-), 2.73 - 2.35 (m, 16H; 4H, >NCH2CH2-; 8H, pip-H; 2H, pip-CH2CH2-; 2H, pip-CH2CH2-), 2.29 (t, 4H; >CH(CH2)2OC(=O)CH2-), 2.10 - 1.99 (m, 8H, -CH=CHCH2-), 1.97 - 1.89 (m, 4H, >CHCH2-), 1.66 - 1.22 (m, 80H, -CH2CH2CH2-, -CH2CH3), 0.88 (t, 12H, -CH2CH3). MS (ESI): m / z=1380.2 ([M+H] + )。 Example 25: Cationic Lipid (E25-1) The preparation process is as follows:[[]]END]] Under nitrogen protection, DCC (0.45 g, 2.2 mmol) was added to a round-bottom flask containing S23-4 (0.75 g, 1.0 mmol), S6-2 (0.71 g, 1.2 mmol) and DMAP (0.03 g, 0.3 mmol) dissolved in dichloromethane (20 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 obtained was purified by column chromatography to obtain cationic lipid E25-1 (1.09 g). 11H NMR (400 MHz, CDCl3) δ: 4.93 - 4.87 (m, 1H, -C(=O)OCH<), 4.12 (t, 4H, -C≡CCH2CH2OC(=O)-), 4.11 (t, 4H, -NHC(=O)OCH2-), 3.17 (s, 2H, pip-CH2C(=O)O-), 3.15 (t, 4H, -CH2NHC(=O)O-), 2.80 - 2.38 (m, 20H; 4H, >NCH2CH2-; 8H, pip-H; 2H, pip-CH2CH2-; 2H, pip-CH2CH2-; 4H, -C≡CCH2CH2OC(=O)-), 2.30 (t, 4H, -(CH2)4CH2C≡C-), 2.18 - 2.09 (m, 4H, -OC(=O)CH2(CH2)6-), 1.65 - 1.23 (m, 88H, -CH2CH2CH2-, -CH2CH3), 0.88 (t, 12H, -CH2CH3). MS (ESI): m / z = 1324.1 ([M+H] + )。 Example 26: Cationic Lipid (E26-1) The preparation process is as follows: Step a: Under nitrogen protection, dissolve compound S7-1 (0.35 g, 2.0 mmol) in acetonitrile (30 mL). While stirring slowly, sequentially add S23-3 (1.82 g, 5.0 mmol) and DIPEA (0.52 g, 4.0 mmol). Stir the reaction at room temperature for about 20 h. After the reaction is completed, concentrate the reaction solution, dissolve it in dichloromethane, and then extract it successively with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution. Then combine the organic phases, dry with anhydrous magnesium sulfate, filter, and concentrate the filtrate. Purify the product by column chromatography to obtain compound S26-1 (1.24 g). Step b: Under nitrogen protection, add DCC (0.45 g, 2.2 mmol) to a round-bottom flask containing S7-5 (0.65 g, 1.0 mmol), S26-1 (0.89 g, 1.2 mmol), and DMAP (0.03 g, 0.3 mmol) dissolved in dichloromethane (20 mL). React at room temperature for 16 h. After the reaction is completed, remove the precipitate by filtration, concentrate the filtrate, and purify the obtained crude product by column chromatography to obtain cationic lipid E26-1 (1.13 g). 11H NMR (400 MHz, CDCl3) δ: 5.45 - 5.25 (m, 8H, -CH=CH-), 4.39 - 4.29 (m, 4H, >CH(CH2OC(=O)2-), 4.24 (t, 2H, pip-CH2CH2OC(=O)-), 4.11 (t, 4H, -NHC(=O)OCH2-), 3.15 (t, 4H, -CH2NHC(=O)O-), 3.02 (q, 1H, >CHC(=O)OCH2-), 2.80 - 2.38 (m, 22H; 4H, >NCH2CH2-; 8H, pip-H; 4H, pip-CH2CH2-; 2H, pip-CH2CH2N<; 4H, -CH=CHCH2CH=CH-), 2.29 (t, 4H, -CH2C(=O)OCH2CH<), 2.03 - 1.97 (m, 8H, -CH=CHCH2-), 1.65 - 1.23 (m, 80H, -CH2CH2CH2-, -CH2CH3), 0.88 (t, 12H, -CH2CH3). MS (ESI): m / z = 1366.2 ([M+H] + )。 Example 27: Cationic Lipid (E27-1) The preparation process is as follows: Step a: Dissolve S1-1 (0.46 g, 2.0 mmol) in dichloromethane solution (20 mL) and cool it to 0 °C in an ice bath. Under vigorous stirring, add (9Z,12Z)-octadeca-9,12-dienal (S27-1, 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. Remove the ice bath and stir the reaction solution at room temperature 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 product twice with dichloromethane (10 mL * 2), wash the combined organic phase with brine (10 mL), dry it with anhydrous magnesium sulfate, filter, concentrate the filtrate to obtain the crude product. Dissolve the crude product in dichloromethane again, add TFA to 0.1 M, react for 4 hours, adjust the pH to neutral, concentrate the reaction solution, add purified water, extract with dichloromethane, dry the extract with anhydrous magnesium sulfate, filter, concentrate the filtrate, and recrystallize to obtain the amino-exposed intermediate S27-2 (1.15 g, 91.8%). Step b: S27-2 (0.63 g, 1.0 mmol) and DIPEA (0.10 g, 0.8 mmol) were successively added to a methanol solution of S1-11 (0.57 g, 1.5 mmol), and the reaction mixture was placed in a reflux apparatus (90 °C) and stirred for an additional 24 h. After the reaction was completed, the reaction mixture was concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E27-1 (0.74 g). 1 H NMR (400 MHz, CDCl3) δ: 5.45 - 5.25 (m, 8H, -CH=CH-), 4.90 - 4.81 (m, 1H, >CHOC(=O)-), 3.71 - 3.61 (m, 1H, -CH(OH)-), 2.84 - 2.24 (m, 24H; 8H, pip-H; 4H, pip-CH2CH2-; 2H, pip-CH2CH2N<; 4H, >NCH2CH2-; 4H, -CH=CHCH2CH=CH-; 2H, -CH2C(=O)O-), 2.03 - 1.97 (m, 8H, -CH=CHCH2-), 1.66 - 1.23 (m, 70H, -CH2CH2CH2-, -CH2CH3), 0.89 (t, 12H, -CH2CH3). MS (ESI): m / z=1008.0 ([M+H] + )。 Example 28: Cationic Lipid (E28-1) The preparation process is as follows: Under nitrogen protection, compound S27-2 (0.63 g, 1.0 mmol) was dissolved in acetonitrile (20 mL). S2-6 (0.66 g, 1.3 mmol) and DIPEA (0.17 g, 1.3 mmol) were successively added with slow stirring, and the mixture was stirred at room temperature for about 20 h. After the reaction was completed, the reaction mixture was concentrated, dissolved in dichloromethane, and then extracted successively with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution. Then the organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. The product was purified by column chromatography to obtain cationic lipid E28-1 (0.87 g). 11H NMR (400 MHz, CDCl3) δ: 5.45 - 5.25 (m, 12H, -CH=CH-), 4.63 (t, 1H, >CH(OCH2)2-), 4.09 - 4.00 (m, 2H, -C(=O)OCH2-), 3.52 - 3.36 (m, 4H, >CH(OCH2)2-), 2.80 - 2.35 (m, 24H; 4H, >NCH2CH2-; 2H, >CHCH2CH2C(=O)O-; 4H, pip-CH2CH2-; 8H, pip-H; 2H, pip-CH2CH2N<; 4H, -CH=CHCH2CH=CH-), 2.11 - 1.82 (m, 18H; 2H, -CH2CH(OCH2)2-; 16H, -CH2CH2CH=CH-), 1.63 - 1.21 (m, 56H, -CH2CH2CH2-, -CH2CH3), 0.87 (t, 12H, -CH2CH3). MS (ESI): m / z = 1048.0 ([M+H] + ). Example 29: Cationic Lipid (E29-1) The preparation process is as follows: Under nitrogen protection, dissolve compound S27-2 (0.63 g, 1.0 mmol) in acetonitrile (20 mL). Add S3-4 (0.72 g, 1.3 mmol) and DIPEA (0.17 g, 1.3 mmol) successively under slow stirring, and stir the reaction at room temperature for about 20 h. After the reaction is completed, concentrate the reaction solution, dissolve it with dichloromethane, then extract it successively with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution. Then combine the organic phases, dry with anhydrous magnesium sulfate, filter, concentrate the filtrate, and purify it by column chromatography to obtain cationic lipid E29-1 (0.92 g). 11H NMR (400 MHz, CDCl3) δ: 5.45 - 5.25 (m, 9H; 1H, -C(=O)OCH<; 8H, -CH=CH-), 4.38 - 4.29 (m, 2H, >CH(CH2OC(=O))2-), 4.19 - 4.13 (m, 2H, >CH(CH2OC(=O))2-), 2.80 - 2.35 (m, 28H; 4H, >NCH2CH2-; 4H, >CHCH2OC(=O)CH2-; 2H, >CHOC(=O)CH2-; 4H, pip-CH2CH2-; 8H, pip-H; 2H, pip-CH2CH2N<; 4H, -CH=CHCH2CH=CH-), 2.03 - 1.97 (m, 8H, -CH=CHCH2-), 1.63 - 1.21 (m, 66H, -CH2CH2CH2-, -CH2CH3), 0.87 (t, 12H, -CH2CH3). MS (ESI): m / z = 1094.0 ([M+H] + ). Example 30: Cationic Lipid (E30-1) The preparation process is as follows: Step a: Under nitrogen protection, dissolve S4-7 (0.75 g, 4.0 mmol) and NaOH (0.16 g, 4.0 mmol) in the prepared 1,4-dioxane / water (2:1, v / v) mixed solution (10 mL), and cool the reaction solution to 0 °C to obtain reaction solution A. Dissolve di-tert-butyl dicarbonate (Boc2O, 1.40 g, 6.4 mmol) in the prepared 1,4-dioxane / water (2:1, v / v) mixed solution (10 mL) to obtain reaction solution B, then slowly add reaction solution B dropwise to reaction solution A, and slowly warm up to room temperature, and react overnight. After the reaction is completed, concentrate the reaction solution, dissolve the residue in water, wash it three times with ethyl acetate (5 mL * 3), adjust the pH to 1 - 2 with HCl (1 M), extract it three times with ethyl acetate (10 mL * 3), combine the organic phases and dry them with anhydrous magnesium sulfate, filter, and concentrate the filtrate to obtain compound S30-1 (1.14 g, 99%), which can be directly used for the next reaction without further purification. Step b: Under nitrogen protection, DCC (1.36 g, 6.6 mmol) was added to a round-bottom flask containing S4-6 (2.03 g, 3.6 mmol), S30-1 (0.86 g, 3.0 mmol) and DMAP (0.09 g, 0.8 mmol) dissolved in dichloromethane (30 mL). The reaction was carried out at room temperature for 16 h. After the reaction was completed, the precipitate was removed by filtration, and the filtrate was concentrated to obtain a crude product. The crude product was dissolved in dichloromethane, TFA was added to 0.1 M, and the reaction was carried out for 4 h. The pH was adjusted to neutral, the reaction solution was concentrated, purified water was added, and the mixture was extracted with dichloromethane. The extract was dried over anhydrous magnesium sulfate, filtered, the filtrate was concentrated, and recrystallization was carried out to obtain compound S30-2 (1.74 g). Step c: S30-2 (1.47 g, 2.0 mmol) and DIPEA (0.15 g, 1.2 mmol) were successively added to a methanol solution of 1,2-epoxytetradecane (S30-3, 1.27 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 E30-1 (1.84 g). 1 H NMR (400 MHz, CDCl3) δ: 5.82 - 5.71 (m, 2H, -C(=O)OCH2CH=CH-), 5.60 - 5.50 (m, 2H, -C(=O)OCH2CH=CH-), 4.93 - 4.86 (m, 1H, -C(=O)OCH<), 4.54 - 4.46 (m, 4H, -C(=O)OCH2CH=CH-), 3.63 - 3.49 (m, 2H, >CHOH), 3.15 (s, 2H, pip-CH2C(=O)O-), 2.93 - 2.32 (m, 16H; 4H, >NCH2CH<; 8H, pip-H; 2H, pip-CH2CH2-; 2H, pip-CH2CH2-), 2.29 (t, 4H, -OC(=O)CH2CH2-), 2.08 - 2.00 (m, 4H, -CH=CHCH2CH2-), 1.65 - 1.19 (m, 84H, -CH2CH2CH2-,-CH2CH3), 0.88 (t, 12H, -CH2CH3). MS (ESI): m / z=1158.9 ([M+H] + )。 Example 31: Cationic lipid (E31-1) The preparation process is as follows: Step a: Under nitrogen protection, DCC (1.36 g, 6.6 mmol) was added to a round-bottom flask containing S6-2 (2.12 g, 3.6 mmol), S30-1 (0.86 g, 3.0 mmol) and DMAP (0.09 g, 0.8 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 to obtain a crude product. The crude product was dissolved in dichloromethane, TFA was added to 0.1 M, the reaction was carried out for 4 h, the pH was adjusted to neutral, the reaction solution was concentrated, purified water was added, extracted with dichloromethane, the extract was dried over anhydrous magnesium sulfate, filtered, the filtrate was concentrated, and recrystallized to obtain compound S31-1 (1.79 g). Step b: Under nitrogen protection, compound S31-1 (1.52 g, 2.0 mmol) was dissolved in acetonitrile (50 mL). S1-14 (1.75 g, 5.0 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 and then dissolved in dichloromethane, and then extracted successively with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution. Then the organic phases were combined, dried over anhydrous magnesium sulfate, filtered, the filtrate was concentrated, and purified by column chromatography to obtain cationic lipid E31-1 (2.16 g). 1 H NMR (400 MHz, CDCl3) δ: 4.93 - 4.87 (m, 1H, -C(=O)OCH<), 4.12 (t, 4H, -C≡CCH2CH2OC(=O)-), 4.04 (t, 4H, >NCH2CH2C(=O)OCH2-), 3.16 (s, 2H, pip-CH2C(=O)O-), 2.80 - 2.38 (m, 28H; 4H, >NCH2CH2-; 8H, pip-H; 2H, pip-CH2CH2-; 2H, pip-CH2CH2-; 8H, -CH2C(=O)O-; 4H, -C≡CCH2CH2OC(=O)-), 2.30 (t, 4H, -(CH2)4CH2C≡C-), 1.84 - 1.76 (m, 4H, -C(=O)OCH2CH2CH2-), 1.65 - 1.23 (m, 84H, -CH2CH2CH2-, -CH2CH3), 0.89 (t, 12H, -CH2CH3). MS (ESI): m / z=1294.1 ([M+H] + )。 Example 32: Cationic lipid (E32-1) The preparation process is as follows: Dissolve S30-2 (1.47 g, 2.0 mmol) in dichloromethane solution (20 mL) and cool it to 0 °C in an ice bath. With vigorous stirring, add S27-1 (1.58 g, 6.0 mmol), and then add NaBH(OAc)3 (1.27 g, 6.0 mmol) in three portions within 10 minutes. Remove the ice bath and stir the reaction mixture at room temperature for 2 h. After the reaction is completed, add NaOH aqueous solution (1 M, 10 mL), stir the reaction mixture for 15 minutes, and then dilute it with water. Extract the product twice with dichloromethane (10 mL * 2), wash the combined organic phases with brine (10 mL), dry over anhydrous magnesium sulfate, filter, concentrate the filtrate, and purify by column chromatography to obtain cationic lipid E32-1 (2.23 g, 92.8%). 1 H NMR (400 MHz, CDCl3) δ: 5.82 - 5.71 (m, 2H, -C(=O)OCH2CH=CH-), 5.56 - 5.54 (m, 2H, -C(=O)OCH2CH=CH-), 5.45 - 5.25 (m, 8H, -(CH2)7CH=CH(CH2)4-), 4.93 - 4.87 (m, 1H, -C(=O)OCH<), 4.55 (t, 4H, -C(=O)OCH2CH=CH-), 3.16 (s, 2H, pip-CH2C(=O)O-), 2.80 - 2.38 (m, 20H; 4H, >NCH2CH2-; 8H, pip-H; 2H, pip-CH2CH2-; 2H, pip-CH2CH2-; 4H, -CH=CHCH2CH=CH-), 2.18 - 2.09 (m, 4H, -OC(=O)CH2(CH2)6-), 2.06 - 1.99 (m, 12H, -CH=CHCH2CH2-), 1.64 - 1.22 (m, 72H, -CH2CH2CH2-,-CH2CH3), 0.91 (t, 12H, -CH2CH3). MS (ESI): m / z=1202.1 ([M+H] + )。 Example 33: Cationic Lipid (E33-1) The preparation process is as follows: Dissolve S31-1 (1.52 g, 2.0 mmol) in dichloromethane solution (20 mL) and cool it to 0 °C in an ice bath. With vigorous stirring, add S27-1 (1.58 g, 6.0 mmol), and then add NaBH(OAc)3 (1.27 g, 6.0 mmol) in three portions within 10 minutes. Remove the ice bath and stir the reaction mixture at room temperature for 2 h. After the reaction is completed, add NaOH aqueous solution (1 M, 10 mL), stir the reaction mixture for 15 minutes, and then dilute it with water. Extract the product twice with dichloromethane (10 mL * 2), wash the combined organic phases with brine (10 mL), dry over anhydrous magnesium sulfate, filter, concentrate the filtrate, and purify by column chromatography to obtain cationic lipid E33-1 (2.28 g, 93.1%). 1 H NMR (400 MHz, CDCl3) δ: 5.45 - 5.25 (m, 8H, -CH=CH-), 4.93 - 4.87 (m, 1H, -C(=O)OCH<), 4.12 (t, 4H, -C≡CCH2CH2OC(=O)-), 3.16 (s, 2H, pip-CH2C(=O)O-), 2.80 - 2.38 (m, 24H; 4H, >NCH2CH2-; 8H, pip-H; 2H, pip-CH2CH2-; 2H, pip-CH2CH2-; 4H, -CH=CHCH2CH=CH-; 4H, -C≡CCH2CH2OC(=O)-), 2.30 (t, 4H, -(CH2)4CH2C≡C-), 2.18 - 2.09 (m, 4H, -OC(=O)CH2(CH2)6-), 2.03 - 1.97 (m, 8H, -CH=CHCH2-), 1.65 - 1.23 (m, 72H, -CH2CH2CH2-, -CH2CH3), 0.90 (t, 12H, -CH2CH3). MS (ESI): m / z=1226.1 ([M+H] + )。 Example 34: Preparation of LNP-mRNA Pharmaceutical Composition and Testing of Its Physicochemical Properties Example 34.1: Preparation of LNP-mRNA Pharmaceutical Composition In this example, an LNP-mRNA pharmaceutical composition (LNP-mRNA) containing Fluc-mRNA was prepared. The phospholipids it contains are all DSPC, the sterol lipids it contains are all cholesterol, and the polyethylene glycolated lipids it contains are all PEG2k-DMG. The difference lies in the cationic 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 at a molar ratio of 50:10:38:1.5 to obtain an ethanol-phase solution (the lipid formulations of each group are shown in Table 1 specifically. The cationic lipids used in the control groups L-CT1 and L-CT2 are the cationic lipids of the prior art, and the cationic lipids of the experimental groups L-1-1 to L-33 are the cationic lipids containing piperazine rings of the present invention); Among them, the cationic lipid used in LCT-1 is C-1, which is prepared by referring to the method disclosed in the patent literature CN115010681A. The cationic lipid used in LCT-2 is C-2, which is prepared by referring to the method disclosed in the patent literature US20220040308A1. The structures of C-1 and C-2 are as follows: 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. Table 1: Summary table of the cationic lipids used in each lipid composition and the particle size and encapsulation efficiency of the LNP-mRNA prepared Example 34.2: Physicochemical property test of the LNP-mRNA pharmaceutical composition Determination of encapsulation efficiency: Use the Quant-it Ribogreen RNA quantification assay kit to determine the encapsulation efficiency of the LNP-mRNA composition. The results show that the lipid compositions of the present invention (L-1-1 to L-33) have a high encapsulation efficiency for nucleic acid drugs (mRNA), all within the range of 80% - 95%, and most of the encapsulation efficiencies are within the range of 90% - 95%. The results indicate that the cationic lipids containing nitrogen heterocycles in each experimental group can encapsulate mRNA well, and most show better encapsulation efficiencies than C-1 and C-2. There are also differences in the encapsulation efficiencies of the cationic lipids containing nitrogen heterocycles with different structures. Determination of particle size: In this example, the particle size of LNP-mRNA is measured by dynamic light scattering (DLS). The measured LNP-mRNA has a high size uniformity, and its PDI is less than 0.3. The particle size of the LNP-mRNA prepared by the lipid composition of the present application is within the range of 80 - 120 nm, meeting the requirements for the particle size of a nucleic acid delivery carrier. Example 35: Biological activity test of the LNP-mRNA pharmaceutical composition (1) Serum stability evaluation Add the above LNP-mRNA into the medium containing 10% fetal bovine serum (FBS), stir at 37 °C, and take samples regularly to measure the particle size change of LNP-mRNA. Analyze the serum stability of the nucleic acid drug preparation by testing its particle size change. The experimental results show that within 7 days, the particle size change of the experimental group is 0-14%, and the particle size change of the experimental group is 2-8%. These results indicate that the LNP-mRNA drug composition prepared with the cationic lipid of the present invention has good serum stability. (2) Cytotoxicity evaluation Prepare a complete DMEM high-glucose medium containing 10% FBS, and prepare working solutions of 0.1, 0.15, 0.2, 0.25, and 0.3 μg / 100 μL of the sample group LNP-mRNA lipid drug compositions (L-1-1 to L-33 and L-CT1 to L-CT2) 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 7×10 3 / well, 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 drug compositions prepared with the cationic lipid of the present invention do 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-1-3 are shown in Figure 8. (3) Evaluation of in vitro transfection effect To investigate the mRNA transfection efficiency of each group of LNP-mRNA compositions prepared in Example 34 of the present invention at the cellular level, luciferase bioluminescence was used for testing. The LNP-mRNA composition preparation was dissolved in the culture medium to prepare the required dose. HeLa cells were used as the cell model, and the cell suspension was inoculated into a 96-well plate with a black-edged transparent bottom at a seeding density of 6,000 cells / well at a dose of 100 μL / well. After inoculation, the cells were incubated in a cell culture incubator for 24 h, and then administered at a dose of 0.2 μg mRNA per well. The blank control group was added with the corresponding dose of free Fluc-mRNA. After 24 hours of transfection, the old culture medium was removed and replaced with a new culture medium containing the substrate of sodium D-luciferin (1.5 mg / mL), and after incubating for 5 minutes, the bioluminescence was detected using a microplate reader. The stronger the fluorescence, the more Fluc-mRNA was transported into the cytoplasm and translated into the corresponding fluorescent protein. The experimental results are shown in Table 2. 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 carriers. This may be because the cationic lipid of the present application contains 3 ionizable tertiary amine structures, and the transfection efficiency of the LNPs prepared therefrom is better than that of L-CT1 and L-CT2 groups prepared from nitrogen-containing heterocyclic cationic lipids in the prior art; comparing the experimental groups L-1-1, L-1-2, L-1-3 and L-1-4, it can be seen that the carbon chain length between the tertiary amine and the linking group ester bond affects the ionizability of the tertiary amine. Within a certain range, the longer the carbon chain length, the higher the transfection efficiency. This may be because the stronger the ionizability, the more nucleic acids are bound and the higher the transfection rate. For example, the carbon chain length between the non-piperazine ring tertiary amine and the ester bond of the cationic lipids E1-1 and E1-2 in L-1-1 and L-1-2 is C2, and the carbon chain length between the non-piperazine ring tertiary amine and the ester bond of the cationic lipids E1-3 and E1-4 in L-1-3 and L-1-4 is C5. Therefore, L-1-3 and L-1-4 show better encapsulation efficiency and transfection rate; in addition, although the groups L-27, L-28, L-29, L-32 and L-33 show relatively high encapsulation efficiency, their transfection rates are not optimal. This may be because E27-1, E28-1, E29-1, E32-1 and E33-1 contain fewer degradable groups, resulting in hindered endosomal escape of mRNA and a lower transfection rate than L-1-3; comparing L-6 and L-8, it can be seen that E8-1 containing a hydroxyl group shows better encapsulation efficiency and transfection rate than E6-1 without a hydroxyl group. This may be because the hydroxyl group can interact with the phosphate group on the nucleic acid through hydrogen bonding, thereby improving the delivery efficiency. Table 2: Results of cell transfection test (4) Evaluation of in vivo transfection effect Lipid nanoparticles L-1-3 were delivered to 6-8-week-old female BALB / c mice at a dose of 10 μg / mouse by 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) show that the lipid nucleic acid drug composition prepared from the cationic lipid of the present invention can achieve efficient in vivo delivery of nucleic acid drugs, and the LNP-mRNA drug composition delivered into the body is mainly distributed in the liver and spleen. The above are only the 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, shall be 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 the present invention gives specific embodiments, it should be understood that the present invention can be further improved. In short, according to the principle of the present invention, this application intends to include any changes, uses, or improvements to the present invention, including 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): or its salt, tautomer, stereoisomer, deuterated compound or solvate; Among them, L d is -(CH2) ta N<, its left end is connected to the piperazine ring, ta is an integer from 1 to 6, and a is 2; L e is C 1-12 alkylene or -CH2CH(OH)-(CH2) tb -, tb is an integer from 1 to 10, -CH2CH(OH)-(CH2) tb the left end of - is connected to the piperazine ring; M is any one of -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -NH-, -O(CH2) s O-, -S-, -S-S-, -C(=O)S-, -SC(=O)-, -NHC(=O)-, -C(=O)NH-, -NHC(=O)NH-, -OC(=O)NH-, -NHC(=O)O-, -SC(=O)NH-, -NHC(=O)S-, -C(=S)-, -OC(=S)-, -C(=S)O-, -OC(=S)O-, -NHC(=S)-, -C(=S)NH-, -NHC(=S)NH-, -OC(=S)NH- and -NHC(=S)O-; R is wherein, tm is an integer from 0 to 6; each occurrence of B1, B2, and B3 is independently a linking bond or C 1-20 alkylene; each occurrence of L1, L2, and L3 is independently a linking bond or L c , L c selected from any one of -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -NH-, -O(CH2) s O-, -S-, -S-S-, -C(=O)S-, -SC(=O)-, -NHC(=O)-, -C(=O)NH-, -NHC(=O)NH-, -OC(=O)NH-, -NHC(=O)O-, -SC(=O)NH-, -NHC(=O)S-, -C(=S)-, -OC(=S)-, -C(=S)O-, -OC(=S)O-, -NHC(=S)-, -C(=S)NH-, -NHC(=S)NH-, -OC(=S)NH- and -NHC(=S)O-; each occurrence of R1, R2, and R3 is independently a linear or branched C 5-30 hydrocarbyl group, and the hydrocarbyl group is an alkyl group, an alkenyl group or an alkynyl group; when B1, B2, L1, and L2 are all linking bonds, L e is -CH2CH(OH)-(CH2) tb -; s is 1, 2 or 3; R g is H or C 1-6 alkyl group.

2. The cationic lipid according to claim 1, wherein The B1, B2, and B3 are selected from any one of the following situations: Case (1): B1, B2, and B3 are each independently C 1-20 an alkylene group; Case (2): B1 and B2 are linking keys, and each occurrence of B3 is independently C 1-20 alkylene; Case (3): B1 and B2 are each independently C 1-20 an alkylene group, and B3 is a linking bond; Situation (4): B1, B2, and B3 are all linking bonds; The aforementioned C 1-20 The alkylene group is preferably C 1-10 alkylene group, and more preferably any one of methylene, ethylene, propylene, butylene, pentylene, hexylene, and heptylene.

3. The cationic lipid according to claim 1, wherein L1, L2, and L3 are any one of the following situations: Case (1): L1, L2, and L3 are each independently L c ; Case (2): One selected from L1, L2, and L3 is a connecting key, and the other two are each independently L c ; preferably, L3 is the connecting key, and L1 and L2 are each independently L c ; Case (3): Any two of L1, L2, and L3 are connection keys, and the other is L c ; Preferably, L1 and L2 are connection keys, and L3 is L c ; Situation (4): L1, L2, and L3 are all linking bonds; More preferably, L1, L2, and L3 are any one of the following situations: Situation (a): L1, L2, and L3 are each independently -OC(=O)-, -C(=O)O-, -C(=O)NH-, -NHC(=O)-, -OC(=O)O-, -NHC(=O)O-, -OC(=O)NH-; Situation (b): L3 is a linking bond, and L1 and L2 are each independently -OC(=O)-, -C(=O)O-, -C(=O)NH-, -NHC(=O)-, -OC(=O)O-, -NHC(=O)O-, -OC(=O)NH-; Situation (c): L1 and L2 are linking bonds, and L3 is selected from -OC(=O)-, -C(=O)O-, -C(=O)NH-, -NHC(=O)-, -OC(=O)O-, -NHC(=O)O-, -OC(=O)NH-; 4. The cationic lipid according to claim 1, wherein The linear C 5-30 hydrocarbyl group is C 5-30 a straight-chain alkyl group, C 5-30 a straight-chain alkenyl group, C 5-30 a straight-chain alkynyl group; preferably each independently is C 5-25 a straight-chain alkyl group, C 5-25 a straight-chain alkenyl group, C 2-25 a straight-chain alkynyl group; the linear C 5-30 hydrocarbyl group is more preferably any one of the following structures: The branched C 5-30 hydrocarbyl group is a branched C 5-30 alkyl group, a branched C 5-30 alkenyl group or a branched C 5-30 alkynyl group, each independently represented as wherein, tn is an integer from 0 to 12; R e , R f are each independently one of C 1-15 alkyl, C 2-15 alkenyl, and C 2-15 alkynyl, preferably R e , R f are each independently selected from any one of butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, pentenyl, hexenyl, heptenyl, octenyl, nonenyl, decenyl; the branched C 5-30 hydrocarbyl is most preferably selected from any one of the following structures:

5. The cationic lipid according to claim 1, wherein, The R1, R2, and R3 are selected from any one of the following situations: Case (1): R1, R2, and R3 are all linear C 5-30 hydrocarbyl groups; Case (2): R1, R2, and R3 are all branched C 5-30 hydrocarbyl groups; Case (3): Any one of R1, R2, and R3 is a linear C 5-30 hydrocarbon group, and the other two are branched C 5-30 hydrocarbon groups; Case (4): Any two of R1, R2, and R3 are linear C 5-30 hydrocarbon groups, and the other is a branched C 5-30 hydrocarbon group; Preferably, R1, R2, and R3 are all linear C 5-30 hydrocarbyl groups.

6. The cationic lipid according to claim 1, wherein The R is selected from any one of the following structures:

7. The cationic lipid according to claim 1, wherein -B3-L3-R3 is independently selected from any one of the following structures:

8. The cationic lipid according to claim 1, wherein The structure of the cationic lipid satisfies any one of the following general formulas: Among them, in general formula (1-A), L1 and L2 are divalent linking groups, and in general formula (1-B), B1, B2, L1, and L2 are all linking bonds at the same time; among them, M is -OC(=O)- or -C(=O)O-; More preferably, the structure of the cationic lipid satisfies any of the following general formulas: Preferably, in the aforementioned general formulas (1-1)-(1-20), B1 and B2 are the same and are a linking bond or C 1-12 alkylene; L1 and L2 are the same and are any one of a linking bond, -O-, -OC(=O)-, -C(=O)O-, -NHC(=O)-, -C(=O)NH-, -OC(=O)O-; R1 and R2 are the same and are linear C 5-30 hydrocarbon group; R3 is a linear C 5-30 hydrocarbon group.

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

10. A lipid composition, characterized in that, Containing the cationic lipid described in any one of claims 1-9.

11. The lipid composition according to claim 10, characterized in that, It also contains one or more of phospholipids, steroid lipids, and polyethylene glycolated lipids; selected from any one of the following situations: Situation (1): It also contains phospholipids; Situation (2): It also contains steroid lipids; Situation (3): It also contains polyethylene glycolated lipids; Situation (4): It also contains phospholipids and steroid lipids; Situation (5): It also contains phospholipids and polyethylene glycolated lipids; Situation (6): It also contains steroid lipids and polyethylene glycolated lipids; Situation (7): It also contains phospholipids, steroid lipids, and polyethylene glycolated lipids; Situation (8): It also contains phospholipids, steroid lipids, polyethylene glycolated lipids, and another cationic lipid; Situation (9): It also contains phospholipids, steroid lipids, polyethylene glycolated lipids, and anionic lipids; More preferably, it also contains three lipids: phospholipids, steroid lipids, and polyethylene glycolated lipids at the same time.

12. The lipid composition according to claim 11, wherein The phospholipids are selected from any one of 1,2-dilinoleoyl-sn-glycero-3-phosphocholine, 1,2-dimyristoyl-sn-glycero-phosphocholine, 1,2-dioleoyl-sn-glycero-3-phosphocholine, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, 1,2-distearoyl-sn-glycero-3-phosphocholine, 1,2-dielaidoyl-sn-glycero-phosphocholine, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, 1,2-di-O-octadecenoyl-sn-glycero-3-phosphocholine, 1-oleoyl-2-cholesteryl succinyl-sn-glycero-3-phosphocholine, 1-hexadecyl-sn-glycero-3-phosphocholine, 1,2-dilinolenoyl-sn-glycero-3-phosphocholine, 1,2-diarachidonoyl-sn-glycero-3-phosphocholine, 1,2-didocosahexaenoyl-sn-glycero-3-phosphocholine, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, 1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, 1,2-dilinoleoyl-sn-glycero-3-phosphoethanolamine, 1,2-dilinolenoyl-sn-glycero-3-phosphoethanolamine, 1,2-diarachidonoyl-sn-glycero-3-phosphoethanolamine, 1,2-didocosahexaenoyl-sn-glycero-3-phosphoethanolamine, 1,2-dioleoyl-sn-glycero-3-phospho-rac-(1-glycerol) sodium salt, dioleoyl phosphatidylserine, dipalmitoyl phosphatidylglycerol, palmitoyl oleoyl phosphatidylethanolamine, distearoyl phosphatidylethanolamine, dipalmitoyl phosphatidylethanolamine, dimyristoyl phosphoethanolamine, 1-stearoyl-2-oleoyl-stearoylethanolamine, 1-stearoyl-2-oleoyl-phosphatidylcholine, sphingomyelin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidic acid, palmitoyl oleoyl phosphatidylcholine, lysophosphatidylcholine and lysophosphatidylethanolamine and their combinations; or the steroid lipids are selected from any one of cholesterol, coprosterol, sitosterol, ergosterol, campesterol, stigmasterol, brassicasterol, tomatine, ursolic acid, α-tocopherol and their combinations; Or the polyethylene glycolated lipid is selected from polyethylene glycol-1,2-dimyristoyl glycerol, polyethylene glycol-distearoyl phosphatidylethanolamine, PEG-cholesterol, polyethylene glycol-diacylglycerol, polyethylene glycol-dialkoxypropyl, specifically including any one of polyethylene glycol 500-dipalmitoyl phosphatidylcholine, polyethylene glycol 2000-dipalmitoyl phosphatidylcholine, polyethylene glycol 500-distearoyl phosphatidylethanolamine, polyethylene glycol 2000-distearoyl phosphatidylethanolamine, polyethylene glycol 500-1,2-dioleoyl phosphatidylethanolamine, polyethylene glycol 2000-1,2-dioleoyl phosphatidylethanolamine, and polyethylene glycol 2000-2,3-dimyristoyl glycerol and its compositions, or the polyethylene glycolated lipid is selected from any one of the following structures and its compositions: wherein, n1 is an integer from 25 to 300, and more preferably n1 is any one of 44, 45, 46, 47, 48; or said another 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)propyl-1-ammonium, 3,6-bis{4-[bis(2-hydroxydodecyl)amino]butyl}piperazine-2,5-dione, 1,1'-((2-(4-(2-((2-(bis(2-hydroxydodecyl)amino)ethyl)(2-hydroxydodecyl)amino)ethyl)piperazin-1-yl)ethyl)azanediyl)bis(dodecan-2-ol), 4-(N,N-dimethylamino)butyric acid (dilinoleoyl) methyl ester, 1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine, ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate), 8-[(2-hydroxyethyl)(6-oxo-6-(undecyloxy)hexyl)amino]octanoic acid (nonadec-9-yl) ester, and ((2-(2-hydroxyethoxy)ethyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate) and its compositions; or said anionic lipid is selected from any one of 1,2-dioleoyl-sn-glycero-3-phosphate sodium salt, 1,2-dimyristoyl-sn-glycero-3-phosphate sodium salt, bis(monooleoylglycerol) phosphate ammonium salt, and cardiolipin and its compositions.

13. The lipid composition according to any one of claims 11 - 12, characterized in that, comprising 20-80% of cationic lipid, 5-16% of phospholipid, 25-55% of steroid lipid, and 0.5-10% of polyethylene glycolated lipid, and said percentages are mole percentages of each lipid in the total lipid.

14. The lipid composition according to claim 13, characterized in that, The mole percentage of said cationic lipid in the total lipid is 30-65%; more preferably any one of 35%, 40%, 45%, 46%, 47%, 48%, 49%, 50%, 55%; or the mole percentage of said phospholipid in the total lipid is 7.5-16%; more preferably any one of 8%, 9%, 10%, 11%, 12%, 16%; or the mole percentage of said steroid lipid in the total lipid is 35-50%, more preferably any one of 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%; or the mole percentage of said polyethylene glycolated lipid in the total lipid is 0.5-5%; preferably 1-3%; more preferably any one of 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2.0%, 2.5%.

15. A lipid pharmaceutical composition, characterized in that, Comprising the lipid composition and a drug according to any one of claims 10 - 14, wherein the drug is selected from any one of nucleic acid drugs, gene vaccines, anti-tumor drugs, small molecule drugs, polypeptide drugs or protein drugs.

16. The lipid pharmaceutical composition according to claim 15, characterized in that, 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.

17. The lipid pharmaceutical composition according to any one of claims 15-16, 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.

18. A lipid pharmaceutical composition preparation, characterized in that, Comprising the lipid drug composition according to any one of claims 15 - 17 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.

19. A liposome or lipid nanoparticle, characterized in that, Comprising the lipid composition according to any one of claims 10 - 14.

20. The liposome or lipid nanoparticle according to claim 19, wherein The 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.

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