Novel amino acid-based cationic lipid and use thereof

Abstract

The present application provides a novel amino acid-based cationic lipid, the structure of which is represented by formula (1), wherein the definition of each symbol is consistent with that described herein. The amino acid-based cationic lipid is a pharmaceutically acceptable, biodegradable, or highly biocompatible lipid, and has the advantages of low toxicity, low immunogenicity, and high biocompatibility. The amino acid or amino acid derivative used as a starting material in the preparation process is simple and readily available, and can be obtained from natural sources or by simple synthesis, offering the advantages of simplicity, safety, and reduced production cost. The novel amino acid-based cationic lipid of the present application comprises a degradable group between an amino acid residue and a lipophilic tail chain, enabling a lipid nanoparticle (LNP) prepared therefrom to be degraded timely within endosomes. This solves the problem in the prior art that LNPs prepared from non-degradable lipids tend to accumulate in endosomes and acidify the endosomal environment, hindering the endosomal escape of drug molecules (such as nucleic acids) and resulting in drugs delivered into cells failing to exert their effects.

Description

A novel amino acid nucleocation lipid and its application Technical Field This application belongs to the field of drug delivery, specifically relating to a pharmaceutical carrier containing an amino acid core of cationic lipid, as well as lipid compositions, lipid pharmaceutical compositions, their formulations and applications containing the cationic lipid. Background Technology Nucleic acid drugs are functional biomolecules based on oligonucleotides (DNA / RNA) that achieve therapeutic effects by regulating gene expression, encompassing various forms such as siRNA, antisense nucleic acids, mRNA, and gene editing elements. Among them, messenger RNA (mRNA), as a medium for transmitting genetic information, can be directly translated into functional proteins in the host cell cytoplasm after in vitro transcription synthesis. It boasts significant advantages such as short development cycles and no risk of genome integration, and has demonstrated significant application value in vaccine development, protein replacement therapy, and tumor immunotherapy. However, the inherent phosphodiester backbone of mRNA molecules is susceptible to nuclease degradation, its negative charge leads to cell membrane penetration barriers, and its poor in vivo stability, severely hindering its clinical translation. Therefore, chemical modification strategies and delivery system development have become two core pathways to overcome the bottlenecks in mRNA drug development. In the field of delivery systems, while viral vectors offer high transfection efficiency, their potential risks of genome insertion, pre-existing immunogenicity, and vector capacity limitations have led to increasingly stringent safety evaluation standards for clinical applications. In contrast, non-viral vectors, with their controllable physicochemical properties and good biocompatibility, are gradually becoming the mainstream development direction for nucleic acid delivery technology. In particular, lipid nanoparticle (LNP) systems, which self-assemble cationic lipids, structural lipids (such as DSPC), cholesterol, and PEG-modified lipids in specific proportions to form core-shell structured nanocomposites, are currently the only FDA-approved mRNA vaccine delivery platform. In this delivery system, cationic lipids are linked to nucleic acids through electrostatic interactions, and their molecular structure directly affects key performance parameters of LNPs, such as encapsulation efficiency, endosome escape ability, and targeting. Although commercially available cationic lipids such as MC3, ALC-0315, and SM-102 have shown promise in some applications, different research systems may yield different optimal cationic lipids, and there remains a need for selectable cationic lipids suitable for routine therapeutic use. Existing technology WO2023133089A1 discloses a cationic lipid containing an amide bond, but each hydrophobic hydrocarbon tail chain contains only one linker, which hinders its in vivo degradation and easily leads to cytotoxicity. Therefore, there is still a need in the art for improved cationic lipids suitable for routine therapeutic use. Summary of the Invention This application provides a novel cationic lipid (shown in formula (1)) and its preparation method, a lipid composition containing the cationic lipid, a lipid drug composition containing the lipid composition and its formulation, a liposome or lipid nanoparticle containing the lipid composition, especially an LNP-nucleic acid drug composition containing the lipid composition and its formulation, which has the advantages of high delivery efficiency, safety and low toxicity, and high biocompatibility, and can improve the therapeutic and / or preventive effects of drugs. The above-mentioned objectives of this application are achieved through the following technical solutions: One embodiment of this application provides a cationic lipid: A cationic lipid, characterized in that it has the structure shown in formula (1): Or its salts, tautomers, stereoisomers, deuterated derivatives or solvates; Where g is an integer from 1 to 6, f is 0 or 1, and n is 1 or 2; L e It is -CH(OH)- or -C(=O)-; N g The portion containing tertiary amines is selected from -NR. a R b Or -N r , where R a R b Each of the Cs can be substituted independently. 1-3 Alkyl groups, where Nr is a heterocyclic group containing a tertiary amine, are represented as... Nr contains at least one nitrogen atom as a cyclic atom, and optionally also contains one oxygen atom, one sulfur atom, or another nitrogen atom as a cyclic atom, with the remaining cyclic atoms being carbon atoms. R c These are groups drawn from the cyclic atom, selected from H, hydroxyl, and -(CH2). tg OH, C 1-6 Alkyl, C 1-6 Any of the alkoxy groups, tg is an integer from 1 to 6; p is R c The quantity, selected from integers from 1 to 6; L1 and L2 are each independently -C(=O)O- or -C(=O)NH-; the right ends of L1 and L2 are connected to B1 and B2 respectively; B1 and B2 are each independently optional substitutes for C. 1-8 Alkylene; L3 and L4 are each independently selected from -C(=O)-, -O-, and -O(CH2). sAny one of O-, -S-, -SS-, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -CH(OH)-, -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)O-, -OC(=S)O-, -NHC(=S)NH-, -NHC(=S)NH-, -OC(=S)NH- and -NHC(=S)O-, where s is 1, 2, 3 or 4; R1 and R2 are each independently C 1-30 Straight-chain hydrocarbon group, C 1-30 Branched hydrocarbon group, C 1-30 hydrocarbon derivative residues or Where t is an integer from 0 to 12, R e R f Each independently is C 1-15 Alkyl, C 2-15 alkenyl and C 2-15 Any of the alkynyl groups; R is C 1-30 Hydrocarbon group or C-aryl group interrupted by ester bond 1-30 hydrocarbon group; The term "optionally substituted" includes both "substituted" and "unsubstituted," and "substituted" means that at least one hydrogen atom is substituted by a substituent selected from -OH, -(CH2). g OH, -R d -C(=O)OR d -OC(=O)R d Any one of -X, where R d C 1-6 Alkyl group, where X is a halogen selected from -F, -Cl, -Br, and -I. This application also provides a lipid composition, wherein the embodiment is as follows: A lipid composition comprising a cationic lipid having the structure shown in formula (1). This application also provides a lipid pharmaceutical composition, the embodiments of which are as follows: A lipid pharmaceutical composition comprising a lipid composition and a drug, wherein the lipid composition comprises a cationic lipid having the structure shown in formula (1), and the drug is selected from any one of nucleic acid drugs, gene vaccines, antitumor drugs, small molecule drugs, polypeptide drugs or protein drugs. This application also provides a lipid pharmaceutical composition formulation, the implementation of which is as follows: A lipid pharmaceutical composition formulation comprising the aforementioned lipid pharmaceutical composition and a pharmaceutically acceptable diluent or excipient. This application also provides a liposome or lipid nanoparticle, implemented as follows: A liposome or lipid nanoparticle containing a lipid composition, wherein the lipid composition contains a cationic lipid with the structure shown in formula (1). Compared with the prior art, this application has the following beneficial effects: This application discloses a novel cationic lipid containing an amino acid core, which constructs a multi-tailed molecular structure with a specific spatial configuration by introducing multiple linear or branched hydrophobic hydrocarbon tail chains. Compared with single-tailed lipids, the cationic lipid containing an amino acid core in this application has an increased cross-sectional area at the hydrophobic end, forming a cone-shaped molecular geometry that promotes membrane fusion and content release. The head group undergoes protonation in an acidic endosome environment (pH 5.0-6.5), forming a positively charged enriched region that can interact with negatively charged components on the cell membrane, generating strong electrostatic attraction, triggering lipid flipping and membrane structure remodeling, enhancing endosome escape, and thus improving nucleic acid release efficiency. The novel cationic lipid containing an amino acid core of this application uses a tertiary amine as the head group, an amino acid as the core, and a saturated or unsaturated hydrocarbon group as the tail chain. Its positive charge binds to negatively charged drugs (such as nucleic acids) through electrostatic interactions, thereby increasing the stability of the drug or nucleic acid in blood circulation. Furthermore, this application uses glutamic acid or aspartic acid, which have good biocompatibility, as the core, further improving the biocompatibility of the cationic lipid. The amino acids and their derivatives are readily available and can be obtained naturally or through simple synthesis, offering advantages such as simplicity, safety, and cost-effective production. The novel cationic lipid of this application contains multiple biodegradable groups at its hydrophobic tail. The presence of these biodegradable groups enables the LNP-drug composition prepared from it to degrade in vivo in a timely manner with low cytotoxicity. This solves the problem in the prior art where LNP-drug compositions prepared from cationic lipids that cannot be degraded or have poor degradation performance accumulate in vivo and acidify the in vivo environment, thus hindering the in vivo escape of drugs (e.g., mRNA) and preventing the drugs delivered into cells from exerting their full effect. Attached Figure Description Figure 1 shows the cytotoxicity test results of the LNP-mRNA drug composition L-9 prepared in Example 31. Figure 2 shows the imaging results of mice after injection of the LNP-mRNA drug composition L-9 prepared in Example 31. Implementation Terminology Explanation In this application, unless otherwise described, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. All patent and other publication disclosures cited herein are incorporated herein in their entirety by reference. In the event of any conflict between any description or interpretation of terms herein and any document incorporated herein by reference, the description and interpretation of the terms below shall prevail. In this application, when the structure involved has isomers, it can be any one of them unless otherwise specified. For example, for a structure with cis-trans isomers, it can be either the cis or trans structure; for a structure with E / Z isomers, it can be either the E or Z structure; and when it is optically active, it can be either levorotatory or dextrorotatory. In this application, the definition of a numerical range includes not only ranges marked with a hyphen (e.g., 0-12), but also ranges marked with a wavy line (e.g., (0~12)) and ranges marked with "to / to" (e.g., 0 to 12, 1 to 12). In this application, unless otherwise specified, integer ranges marked as intervals can represent groups of all integers within that range, and the range includes two endpoints. For example, the integer range 0-12 represents the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12. The numerical ranges in this application, including but not limited to ranges of integers, non-integers, percentages, and fractions, all include two endpoints unless otherwise specified. The numerical values ​​used in this application, when referring to "about" or "around," generally refer to a range of ±10%, which may be increased to ±15% in some cases, but not exceeding ±20%. A preset value is used as the base. For example, if steroid lipids account for approximately 40% of the total lipids, it can generally be considered that the molar percentage of steroid lipids includes 30%-50%. In this application, unless otherwise specified, "any" includes any one, any two, or any two or more. In this application, unless otherwise specified, the terms “comprising,” “including,” and “containing,” as well as similar expressions, shall be interpreted in an open and inclusive sense as “including but not limited to.” In this application, two or more objects are "independently preferred". When there are multiple levels of preferred options, it is not required that they are all selected from the same level of preferred options. One can be a wide range of preferred options and the other a narrow range of preferred options, or one can be the widest range and the other any preferred option, or they can be selected from the same level of preferred options. In this application, "each occurrence independently constitutes" not only refers to different groups being able to independently constitute any option in the definition, but also indicates that when appearing at different positions within the same group, they can also independently constitute any option in the definition, such as "each occurrence independently constitutes a linking bond, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -C(=O)-, -O-, -NH-, -O(CR)-, -OC(=O ... c R c ) s O-, -S-, -C(=O)S-, -SC(=O)-, -NR c C(=O)-、-C(=O)NR c -、-NR c C(=O)NR c -、-OC(=O)NR c -、-NR c C(=O)O-、-SC(=O)NR c -and-NR c Any one of C(=O)S-, where R c Each time it appears, it is independently a hydrogen atom or a carbon atom. 1-12 alkyl group, in the group "-NR" c C(=O)NR c In the "-", there are two R's c Each is independently a hydrogen atom or a carbon atom. 1-12 Alkyl, i.e., two Rs c They can be the same or different. In this application, the divalent linking group, such as alkylene group, arylene group, amide bond, etc., can be selected from either of the two linking ends when it is linked to other groups unless otherwise specified. For example, when an amide bond is used as the divalent linking group between Group A and Group B, it can be GroupA-C(=O)NH-GroupB or GroupB-NHC(=O)-GroupA. In this application, when the end group of the linking group in the structural formula is easily confused with the substituents contained in the linking group, the following method is adopted: To mark the positions where other groups are attached in the linker, such as in the structural formula. In, the method adopted The two positions in the divalent linker that connect to other groups are marked. The two structural formulas mentioned above represent -CH(CH2CH2CH3)2- and -CH2CH2CH(CH3)2-CH2CH2-, respectively. In this application, the range of carbon atoms in a group is indicated by a subscript at the subscript position of C, representing the number of carbon atoms in the group, for example, C1-12 Indicates "having 1 to 12 carbon atoms", C 1-30 It indicates "having 1 to 30 carbon atoms". "Substituted C" 1-12 "alkyl" refers to C 1-12 Compounds obtained by substituting hydrogen atoms of alkyl groups. "C" 1-12 "Substituted alkyl" refers to compounds in which the hydrogen atoms of an alkyl group are substituted, resulting in compounds with 1-12 carbon atoms. For example, when a group can be selected from C... 1-12 When alkylene is used, it can be selected from any number of carbon atoms in the range indicated by the subscript, i.e., selected from C1, C2, C3, C4, C5, C6, C7, C8, C9, ... 10 C 11 C 12 Any alkylene group. In this application, unless otherwise specified, subscripts in the form of intervals indicate any integer selected from the range, which includes both endpoints. In this application, "base" can be referred to as "bond" without changing its meaning. For example, an ether group (-O-) can also be called an ether bond, and an ester group (-OC(=O)- or -C(=O)O-) can also be called an ester bond. In this application, the "carbon chain length" between two groups refers to the shortest number of carbons excluding the group itself. For example, the carbon chain length between the two ester bonds of -OC(=O)CH2CH2OC(=O)- and -OC(=O)CH(CH3)CH2OC(=O)- is 2 (also referred to as C2), and the carbon chain length between the two ester bonds of -OC(=O)CH2CH2OCH2CH2OC(=O)- is C4 (also referred to as C4). In this application, heteroatoms are not specifically limited, including but not limited to O, S, N, P, Si, F, Cl, Br, I, B, etc. In this application, the heteroatom used for substitution is referred to as a "substituent atom", and any group used for substitution is referred to as a "substituent". In this application, "substituted" means any of the aforementioned groups (e.g., aliphatic hydrocarbon group, hydrocarbon group, alkyl group, or alkylene group) in which at least one hydrogen atom is substituted by a bond connected to a non-hydrogen atom, such as, but not limited to: halogen atoms such as F, Cl, Br, and I; oxo groups (=O); hydroxyl groups (-OH); alkyloxy groups (-OR). d , where R d C 1-12 Alkyl group; Carboxyl group (-COOH); Amine group (-NR) c R c Two Rs c Each independently represents H and C. 1-12 Alkyl); C 1-12Alkyl and cycloalkyl. In some embodiments, the substituent is C. 1-12 Alkyl group. In other embodiments, the substituent is cycloalkyl. In other embodiments, the substituent is a halogenated group, such as a fluorinated group. In other embodiments, the substituent is an oxogroup. 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 this application, "optional" or "optionally" (e.g., optionally substituted) means that the event described thereafter may or may not occur, and the description includes instances where the event or condition occurs and instances where the event or condition does not occur. For example, "optionally substituted hydrocarbon group" means that the hydrocarbon group may or may not be substituted, and the description includes substituted hydrocarbon groups and unsubstituted hydrocarbon groups. In this application, a compound or a group can be simultaneously substituted and hybridized, for example, a hydrogen atom can be substituted by a nitrophenyl group, or -CH2-CH2-CH2- can be replaced by -CH2-S-CH(CH3)-. In this application, "linking bond" refers to a bond that only serves a connecting function and does not contain any atoms. When a group is defined as a linking bond, it means that the group may not exist. In this application, a "group" containing at least one atom refers to a free radical formed by the loss of one or more atoms from a compound. A group formed after the loss of a portion of a compound is also called a residue. The valence state of a group is not particularly limited, but can be categorized as monovalent, divalent, trivalent, tetravalent, ..., 100valent groups, etc. Groups with a valence of 2 or greater are collectively referred to as linking groups. Linking groups can also contain only one atom, such as oxygen or thio groups. In this application, "hydrocarbon" refers to hydrocarbons composed of carbon atoms and hydrogen atoms. In this application, hydrocarbons are classified into two types according to the hydrocarbon group: aliphatic hydrocarbons and aromatic hydrocarbons. Hydrocarbons that do not contain any type of benzene ring or substituted benzene group are defined as aliphatic hydrocarbons. Hydrocarbons containing at least one benzene ring or substituted benzene group are defined as aromatic hydrocarbons. Aromatic hydrocarbons may contain aliphatic hydrocarbon groups, such as toluene, diphenylmethane, and 2,3-dihydroindene. In this invention, hydrocarbons are classified into two types based on their degree of saturation: 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. Examples include, but are not limited to, alkenes (containing double bonds), alkynes (containing triple bonds), and dienes (containing conjugated double bonds). When the aliphatic portion of an aromatic hydrocarbon is saturated, it is also called an aromatic alkane, such as toluene. In this application, there are no particular restrictions on the structure of the hydrocarbon, which can be a straight-chain structure without side groups, a branched structure with side groups, a cyclic structure, a dendritic structure, a comb-like structure, a hyperbranched structure, etc. Unless otherwise defined, straight-chain structures without side groups, branched structures with side groups, and cyclic structures are preferred, corresponding to straight-chain hydrocarbons, branched hydrocarbons, and cyclic hydrocarbons, respectively. Hydrocarbons without cyclic structures are collectively referred to as open-chain hydrocarbons, including but not limited to straight-chain structures without side groups and branched structures 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 this application, "hydrocarbon group" refers to a residue formed after a hydrocarbon loses at least one hydrogen atom. Based on the number of hydrogen atoms lost, hydrocarbon groups can be classified as monovalent (losing one hydrogen atom), divalent (losing two hydrogen atoms, also called a hydrocarbon subgroup), trivalent (losing three hydrogen atoms), and so on. When n hydrogen atoms are lost, the valence state of the resulting hydrocarbon group is n. Unless otherwise specified, "hydrocarbon group" in this application specifically refers to a monovalent hydrocarbon group. Unless otherwise explicitly stated in this specification, hydrocarbon groups are optionally substituted. In this application, the source of the hydrocarbon group is not particularly limited. For example, it can originate from aliphatic or aromatic hydrocarbons, saturated or unsaturated hydrocarbons, straight-chain hydrocarbons, branched-chain hydrocarbons, or cyclic hydrocarbons, as well as hydrocarbons or heterocyclic hydrocarbons, etc. From the perspective of saturation, it can originate from alkanes, alkenes, alkynes, dienes, etc.; for cyclic hydrocarbons, it can originate from alicyclic or aromatic hydrocarbons, monocyclic or polycyclic hydrocarbons; for heterocyclic hydrocarbons, it can originate from alicyclic heterocyclic hydrocarbons or aromatic heterocyclic hydrocarbons. In this application, "aliphatic hydrocarbon group" refers to a residue formed after an aliphatic hydrocarbon loses at least one hydrogen atom. Unless otherwise specified, "aliphatic hydrocarbon group" in this application specifically refers to a monovalent aliphatic hydrocarbon group. Aliphatic hydrocarbon groups include saturated aliphatic hydrocarbon groups and unsaturated aliphatic hydrocarbon groups. Unless otherwise expressly stated in this specification, aliphatic hydrocarbon groups are optionally substituted. In this application, "alkyl" refers to a hydrocarbon group formed from an alkane. Unless otherwise specified, it refers to a hydrocarbon group formed by losing a hydrogen atom at any position, and can be straight-chain or branched, substituted or unsubstituted. Specifically, propyl refers to either n-propyl or isopropyl, and propylene refers to either 1,3-propylene, 1,2-propylene, or isopropylene. Unless otherwise expressly stated in this specification, alkyl groups are optionally substituted. In this application, "unsaturated hydrocarbon group" refers to the hydrocarbon group formed by the loss of hydrogen atoms from an unsaturated hydrocarbon. Hydrocarbon groups formed by the loss of hydrogen atoms from unsaturated carbon atoms in unsaturated hydrocarbons can be classified into alkenyl, alkynyl, dienyl, etc. In this application, "alkenyl" refers to a straight-chain or branched-chain hydrocarbon group containing at least one carbon-carbon double bond formed by the loss of a hydrogen atom at any position of an alkene. For example, "C 2-15"Alkenyl" means a straight-chain or branched alkenyl group comprising 2-15 carbon atoms and at least one carbon-carbon double bond; that is, an alkenyl group can include one, two, three, four, or more carbon-carbon double bonds. Unless otherwise specifically stated, alkenyl groups as used herein refer to both unsubstituted and substituted alkenyl groups. Unless otherwise expressly stated in this specification, alkenyl groups are optionally substituted. In this application, "alkynyl" refers to a straight-chain or branched-chain hydrocarbon group containing at least one carbon-carbon triple bond formed by the loss of a hydrogen atom at any position in an alkyne. For example, "C 2-15 "Alynyl" means a straight-chain or branched alkynyl group comprising 2-15 carbon atoms and at least one carbon-carbon triple bond. An alkynyl group may include one, two, three, four, or more carbon-carbon triple bonds. Unless otherwise specified, the alkynyl group referred to herein means both unsubstituted and substituted alkynyl groups. Unless otherwise expressly stated in this specification, the alkynyl group is optionally substituted. In this application, "hydroalkyl group" or "hydroalkyl group chain" refers to a straight or branched divalent hydrocarbon chain in which the remainder of a molecule is attached to a free radical group, consisting only of carbon and hydrogen, and may be saturated or unsaturated. For example, a hydroalkyl group (C1) having one to twenty-four carbon atoms. 1-24 Hydroxyl group (C1-C2), having one to twelve carbon atoms. 1-12 (Hydroxyyl groups), specifically, for example, methylene, ethylene, propylene, n-butylene, vinylene, propenylene, n-butenylene, propynylene, n-butynylene, etc. Unless otherwise expressly stated in this specification, hydroxyyl groups are optionally substituted. In this application, "alkylene" refers to a divalent alkyl group, including open-chain alkylene and divalent cycloalkyl. Open-chain alkylene refers to a divalent alkyl group that does not contain a cyclic structure, and divalent cycloalkyl refers to a divalent alkyl group that contains a cyclic structure. Unless otherwise expressly stated in this specification, alkylene is optionally substituted. In this application, "molecular weight" represents the mass of a compound molecule, and "average molecular weight" represents the mass of a general formula compound component in a macroscopic substance. Unless otherwise specified, the molecular weight of a polymer refers to the "average molecular weight," generally meaning "number-average molecular weight" M. n The number-average molecular weight can refer to the molecular weight of either polydisperse blocks or substances, or monodisperse blocks or substances. Unless otherwise specified, the unit of measurement for "molecular weight" and "average molecular weight" is Daltons (Da). The degree of polymerization of polymers can be used to represent the number of repeating units in the molecule (e.g., vinyl oxide units and EO units in PEG). Accordingly, the average degree of polymerization, number-average degree of polymerization, or number of EO units is used to characterize the average or number-mean of the number of repeating units; unless otherwise specified, the exponential degree of polymerization is used. In this application, percentages, "about", generally refer to ±0.5%. In this application, the terms "stable" and "degradable" for a functional group are relative concepts. Detailed examples of stable and degradable functional groups can be found in CN113402405A.

[0134] -

[0145] part. In this application, "hydroxyl protecting group" includes all groups that can be used as protecting groups for the hydroxyl group in general. Preferably, the hydroxyl protecting group is an alkyl acyl (e.g., acetyl, tert-butyryl), aralkyl acyl (e.g., benzyl), benzyl, triphenylmethyl, trimethylsilyl, tert-butyldimethylsilyl, allyl, acetal, or ketal. The removal of the acetyl group is generally carried out under alkaline conditions, most commonly by ammonolysis of NH3 / MeOH and methanololysis catalyzed by methanol anion; benzyl is easily removed by palladium-catalyzed hydrogenolysis in neutral solution at room temperature, or by reduction cleavage with metallic sodium in ethanol or liquid ammonia; triphenylmethyl is generally removed by catalytic hydrogenolysis; trimethylsilyl is usually removed using reagents containing fluoride ions (e.g., tetrabutylamine fluoride / anhydrous THF); tert-butyldimethylsilyl ether is relatively stable and can withstand the ester hydrolysis conditions of alcoholic potassium hydroxide and mild reducing conditions (e.g., Zn / CH3OH), and can be removed by fluoride ions (e.g., Bu4N). + F - It can be removed in tetrahydrofuran solution, or it can be removed with aqueous acetic acid at room temperature. In this application, "carboxyl protecting group" refers to a protecting group that can be converted into a carboxyl group through hydrolysis or deprotection reaction. The carboxyl protecting group is preferably alkyl (e.g., methyl, ethyl, tert-butyl) or aralkyl (e.g., benzyl), more preferably tert-butyl (tBu), methyl (Me), or ethyl (Et). In this application, "protected carboxyl group" refers to the group formed after the carboxyl group is protected by a suitable carboxyl protecting group, preferably methoxycarbonyl, ethoxycarbonyl, tert-butyloxycarbonyl, or benzyloxycarbonyl. The carboxyl protecting group can be removed by hydrolysis under acid or base catalysis, and occasionally by thermal decomposition. For example, tert-butyl can be removed under mild acidic conditions, and benzyl can be removed by hydrogenolysis. The reagent for removing the carboxyl protecting group is selected from TFA, H2O, LiOH, NaOH, KOH, MeOH, EtOH, and combinations thereof, preferably a combination of TFA and H2O, a combination of LiOH and MeOH, or a combination of LiOH and EtOH. The protected carboxyl group is deprotected to produce the corresponding free acid, 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 this application, "amino protecting group" includes all groups that can be used as protecting groups for amino groups in general, such as aryl C. 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkyl, C 1-6Alkoxycarbonyl, aryloxycarbonyl, C 1-6 Alkyl sulfonyl, aryl sulfonyl, or silyl groups are preferred. The amino protecting group is preferably Boc tert-butoxycarbonyl, Moz p-methoxybenzyloxycarbonyl, or Fmoc 9-fluorene-methoxycarbonyl. The reagent for removing the amino protecting group is selected from TFA, H2O, LiOH, MeOH, EtOH, and combinations thereof, preferably combinations of TFA and H2O, LiOH and MeOH, or LiOH and EtOH. The reagent for removing the Boc protecting group is TFA or HCl / EA; TFA is preferred. The deprotecting agent used in the Fmoc protecting group removal reaction is a solution of N,N-dimethylformamide (DMF) containing 20% ​​piperidine. In this application, "cationic lipid" refers to lipids that contain a positive charge or are ionizable in their entirety. "Cation" refers to a corresponding structure that is permanently or non-permanently positively charged in response to certain conditions (e.g., pH). Therefore, cations include both permanent cations and cationizable cations. A permanent cation is a compound, group, or atom that carries a positive charge at any pH or hydrogen ion activity in its environment. Typically, a positive charge arises from the presence of quaternary ammonium atoms. When a compound carries multiple such positive charges, it can be called a permanent cation. A cationizable cation is a compound, group, or atom that carries a positive charge at lower pH and no charge at higher pH in its environment. Additionally, in non-aqueous environments where pH cannot be determined, cationizable compounds, groups, or atoms carry a positive charge at high hydrogen ion concentrations and no charge at low hydrogen ion concentrations or activity. It depends on the individual properties of the cationizable or polycationizable compound, particularly the pKa of the corresponding cationizable group or atom, which determines whether it carries a charge or no charge at the stated pH or hydrogen ion concentration. In a diluted aqueous environment, the so-called Henderson-Hasselbalch equation, well known to those skilled in the art, can be used to estimate the fraction of positively charged cationizable compounds, groups, or atoms. For example, in some embodiments, if a compound or portion is cationizable, it is preferably positively charged at a pH of about 1 to 9, preferably 4 to 9, 5 to 8, or even 6 to 8, more preferably at a pH equal to or below 9, equal to or below 8, equal to or below 7, and most preferably at physiological pH (e.g., about 7.3 to 7.4), i.e., under physiological conditions, particularly under physiological conditions of cells in vivo. In other embodiments, it is preferred that the cationizable compound or portion is primarily neutral at physiological pH (e.g., about 7.0-7.4) but becomes positively charged at lower pH values. In some embodiments, the preferred range of the pKa of the cationizable compound or portion is about 5 to about 7. In this application, lipid nanoparticles, cationic peptides, proteins, polysaccharides, lipids, or polymers are uncharged, neutrally charged, or electrically neutral under physiological conditions, particularly under in vivo cellular conditions. Cationic peptides or proteins preferably contain a large number of cationic amino acids, such as Arg, His, Lys, or Orn (especially more cationic amino acids than anionic amino acid residues like Asp or Glu) or contain components primarily composed of cationic amino acid residues. The term "cationic" can also refer to "polycationic" components / chemical cationic components / compounds, and can also refer to cationic lipids capable of carrying a positive charge. For example, cationic lipids contain one or more positively charged amine groups, and preferably cationic lipids are ionizable, allowing them to exist in a positively charged or neutral form depending on pH. The ionization of cationic lipids affects the surface charge of lipid nanoparticles (LNPs) under different pH conditions. This charge state can influence plasma protein uptake, blood clearance and tissue distribution, and the ability to form non-bilayer structures crucial for intracellular nucleic acid delivery. In this application, "polyethylene glycol lipid" refers to a molecule that includes both a lipid portion and a polyethylene glycol portion. In this application, "neutral lipid" refers to any of a number of lipid substances that exist in the form of a neutral or neutral zwitterion at a selected pH, preferably phospholipids, which may be synthetic or of natural origin. In this application, "steroid lipids" refers to steroids or steroid analogues. In this application, "amino acid residue" includes amino acids with a hydrogen atom removed from the amino group and / or a hydroxyl group removed from the carboxyl group and / or a hydrogen atom removed from the thiol group and / or the amino group protected and / or the carboxyl group protected and / or the thiol group protected. Loosely speaking, an amino acid residue may be referred to as an amino acid. The source of the amino acids in this application is not particularly limited unless specifically specified; they can be of natural origin, non-natural origin, or a mixture of both. The structural type of the amino acids in this application is not particularly limited unless specifically specified; they can refer to L-type, D-type, or a mixture of both. In one embodiment of this application, the amino acids are polar amino acids, specifically aspartic acid (Asp) and glutamic acid (Glu). The variations in this application refer to any chemical change process, such as oxidation, reduction, hydration, dehydration, electron rearrangement, structural rearrangement, salt complexation and decomplexation, ionization, protonation, deprotonation, substitution, deprotection, or alteration of the leaving group, that can transform the structure of the target functional group. In this application, "variable form of functional group" refers to a functional group that remains active (still a functional group) after undergoing at least one chemical change process, such as oxidation, reduction, hydration, dehydration, electron rearrangement, structural rearrangement, salt complexation and decomplexation, ionization, protonation, deprotonation, substitution, deprotection, or change of leaving group, or an inactive form after being protected. In this application, "any suitable linker," "any suitable functional group," etc., refers to a structure that conforms to the basic principles of chemical structure and enables the preparation method of this application to be successfully implemented. Chemical structures described in this way can be regarded as having a clear and definite scope. In this application, when at least two structural types are listed, the “arbitrary combination” of the listed structural types refers to the combination of any two or more structures among the aforementioned related structural types; and there is no limitation on the number of structural units. The number of any structural unit can be zero, one or more. When the number of structural units of the same type is greater than one, they can be structural units with the same or different chemical structures, and the total number of constituting units is at least two. For example, any combination of alkylene, divalent cycloalkyl, divalent cycloalkenyl, divalent cycloynyl, divalent cyclodienyl, aromatic, carbon-carbon double bond, carbon-carbon triple bond, conjugated carbon-carbon double bond, divalent alicyclic linker, divalent aromatic heterocyclic linker, and carbon chain linker with heteroatom-containing side group. Examples include -Ph-CH2-Ph-(aromatic-alkylene-aromatic), -CH2-Ph-CH2CH2-(alkylene-aromatic-alkylene, where the number of alkylene groups is 2 and they have different chemical structures), or the structure where the benzene ring is replaced by a hexane, diazahexane, or 1-(2-pyridyl)hexahydro-1H-1,4-diazaphene. Another example is cycloalkenyl hydrocarbon group = cycloalkenyl + alkylene group = cycloalkenyl as a substituent of the hydrocarbon group, and cyclodienyl hydrocarbon group = cyclodienyl as a substituent of the hydrocarbon group. In this application, "N / P ratio" refers to the molar ratio of nitrogen atoms in cationic lipids to phosphate in nucleic acids. In this application, "nucleic acid" refers to DNA or RNA or a modified form thereof, which contains purine or pyrimidine bases present in DNA (adenine "A", cytosine "C", guanine "G", thymine "T") or purine or pyrimidine bases present in RNA (adenine "A", cytosine "C", guanine "G", uracil "U"). In this application, "RNA" refers to ribonucleic acid, which 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 cap structures, chain-terminating nucleosides, stem-loops, polyadenylated sequences, and / or polyadenylated signals. RNA may be a nucleotide sequence encoding a specific polypeptide, or it may be messenger RNA (mRNA). Translation of mRNA encoding a specific polypeptide, for example, in vivo translation of mRNA within mammalian cells, can produce the encoded polypeptide. RNA may be selected from any of the following: small interfering RNA (siRNA), asymmetric interfering RNA (aiRNA), microRNA (miRNA), Dicer-substrate RNA (dsRNA), small hairpin RNA (shRNA), mRNA, single-stranded guide RNA (sgRNA), self-amplifying RNA (saran), circular RNA (circRNA), Cas9 mRNA, and mixtures thereof. In this application, antisense oligonucleotides or small interfering RNA (siRNA) can inhibit the expression of target genes and target proteins in vitro or in vivo. In this application, FLuc mRNA can express luciferase protein, which emits bioluminescence in the presence of luciferin substrate. Therefore, FLuc is often used in mammalian cell culture to measure gene expression and cell activity. In this application, "inhibition of target gene expression" refers to the ability of nucleic acid to silence, reduce, or inhibit the expression of a target gene. To test the degree of gene silencing, a test sample (e.g., a cell sample in a culture medium expressing the target gene) is exposed to nucleic acid that inhibits target gene expression. The expression of the target gene in the test sample or test animal is compared to the expression of the target gene in a control sample (e.g., a cell sample in a culture medium expressing the target gene) that has not been exposed to or treated with nucleic acid. The expression of the target gene in the control sample can be specified as a value of 100%. In a particular embodiment, inhibition of target gene expression is achieved when the target gene expression level in the test sample is approximately 95%, 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, 50%, 45%, 40%, 35%, 30%, 25%, 20%, 15%, 10%, 5%, or 0% relative to the target gene expression level in the control sample or control mammal. In this application, the methods for determining the expression level of target genes include, but are not limited to, dot blot, northern blot, in situ hybridization, ELISA, immunoprecipitation, enzyme action, and phenotypic determination. In this application, "transfection" refers to the introduction of a species (e.g., RNA) into a cell. Transfection can occur, for example, in vitro, outside the body, or in vivo. In this application, "antigen" typically refers to a substance that can be recognized by the immune system, preferably by the adaptive immune system, and capable of triggering an antigen-specific immune response, for example, by forming antibodies and / or antigen-specific T cells as part of an adaptive immune response. Typically, an antigen can be or may contain a peptide or protein that can be presented to T cells by the MHC. In the sense of this application, an antigen can be the translation product of a 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 as antigens. In this application, "delivery" means providing an entity to a target. For example, delivering a drug and / or a therapeutic and / or preventative agent to a subject, said subject being tissues and / or cells of a human and / or other animal. In this application, "pharmaceutically acceptable carrier" refers to a diluent, excipient, vehicle, or medium that is administered co-administered with a therapeutic agent and is suitable, to the extent of reasonable medical judgment, for contact with human and / or other animal tissues without excessive toxicity, irritation, allergic reactions, or other problems or complications commensurate with a reasonable benefit / risk ratio. Pharmaceutically acceptable carriers that may be used in the pharmaceutical compositions of this application include, but are not limited to, sterile liquids such as water and oils, including those of petroleum, animal, plant, or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil, etc. Water is an exemplary carrier when the pharmaceutical composition is administered intravenously. Physiological saline and aqueous solutions of glucose and glycerol may also be used as liquid carriers, particularly for injectable solutions. Suitable pharmaceutical excipients include starch, glucose, lactose, sucrose, gelatin, maltose, chalk, silica gel, sodium stearate, glyceryl monostearate, talc, sodium chloride, skim milk powder, glycerol, propylene glycol, water, ethanol, etc. The compositions may also contain small amounts of wetting agents, emulsifiers, or pH buffers as needed. Oral formulations may contain standard carriers such as pharmaceutical-grade mannitol, lactose, starch, magnesium stearate, sodium saccharin, cellulose, and magnesium carbonate. Specifically, excipients include, but are not limited to, anti-adhesion agents, antioxidants, binders, coatings, compression aids, disintegrants, dyes (pigments), modifiers, emulsifiers, fillers (diluents), film-forming agents or coatings, flavorings, fragrances, flow enhancers, lubricants, preservatives, printing inks, adsorbents, suspending or dispersing agents, sweeteners, 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, croscarmellose polyvinylpyrrolidone, citric acid, crospovidone, cysteine, ethyl cellulose, gelatin, hydroxypropyl cellulose, hydroxypropyl methylcellulose, lactose, magnesium stearate, maltitol, mannitol, methionine, methylcellulose, methylparaben, microcrystalline cellulose, polyethylene glycol, polyvinylpyrrolidone, povidone, pregelatinized starch, phenylparaben, retinyl palmitate, shellac, silica, sodium carboxymethyl cellulose, sodium citrate, sodium glycolate starch, sorbitol, starch (corn), stearic acid, sucrose, talc, titanium dioxide, vitamin A, vitamin E (α-tocopherol), vitamin C, and xylitol. In this application, the vaccine is a prophylactic or therapeutic material that provides at least one antigen or antigenic function. The antigen or antigenic function can stimulate the body's adaptive immune system to provide an adaptive immune response. In this application, "treatment" refers to the handling and care of a patient in order to combat a disease, obstacle, or symptom, intended to include delaying the progression of the disease, obstacle, or symptom, alleviating or mitigating symptoms and complications, and / or curing or eliminating the disease, obstacle, or symptom. The patient to be treated is preferably a mammal, especially a human. 1. Cationic lipids One implementation method of this application: A cationic lipid having the structure shown in formula (1), Or its salts, tautomers, stereoisomers, deuterated derivatives or solvates; Where g is an integer from 1 to 6, f is 0 or 1, and n is 1 or 2; L e It is -CH(OH)- or -C(=O)-; N g The portion containing tertiary amines is selected from -NR. a R b Or -N r , where R a R b Each of the Cs can be substituted independently. 1-3 Alkyl groups, where Nr is a heterocyclic group containing a tertiary amine, are represented as... Nr contains at least one nitrogen atom as a cyclic atom, and optionally also contains one oxygen atom, one sulfur atom, or another nitrogen atom as a cyclic atom, with the remaining cyclic atoms being carbon atoms. R c These are groups drawn from the cyclic atom, selected from H, hydroxyl, and -(CH2). tg OH, C 1-6 Alkyl, C 1-6 Any of the alkoxy groups, tg is an integer from 1 to 6; p is R c The quantity, selected from integers from 1 to 6; L1 and L2 are each independently -C(=O)O- or -C(=O)NH-; the right ends of L1 and L2 are connected to B1 and B2 respectively; B1 and B2 are each independently optional substitutes for C. 1-8 Alkylene; L3 and L4 are each independently selected from -C(=O)-, -O-, and -O(CH2). s Any one of O-, -S-, -SS-, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -CH(OH)-, -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)O-, -OC(=S)O-, -NHC(=S)NH-, -NHC(=S)NH-, -OC(=S)NH- and -NHC(=S)O-, where s is 1, 2, 3 or 4; R1 and R2 are each independently C 1-30 Straight-chain hydrocarbon group, C 1-30 Branched hydrocarbon group, C 1-30 hydrocarbon derivative residues or Where t is an integer from 0 to 12, R e R f Each independently is C 1-15 Alkyl, C 2-15 alkenyl and C 2-15 Any of the alkynyl groups; R is C 1-30 Hydrocarbon group or C-aryl group interrupted by ester bond 1-30 hydrocarbon group; The term "optionally substituted" includes both "substituted" and "unsubstituted," and "substituted" means that at least one hydrogen atom is substituted by a substituent selected from -OH, -(CH2). g OH, -R d -C(=O)OR d -OC(=O)R d Any one of -X, where R d C 1-6 Alkyl group, where X is a halogen selected from -F, -Cl, -Br, and -I. 1 . 1.N g In this application, N g It contains the tertiary amine portion. In one embodiment of this application, the N g Selected from Any one of them; preferably Any one of them; more preferably Any one of them. 1.2. R1, R2 In this application, R1 and R2 are each independently C. 5-30 Straight-chain hydrocarbon group, C 5-30 Branched hydrocarbon group, C 5-30 hydrocarbon derivative residues or The C 5-30 The branched hydrocarbon group is C 5-30 Branched alkyl, C 5-30 Branched alkenyl or C5-30 Branched alkynyl groups, each independently represented as The C 5-30 Hydrocarbon derivative residues are represented as Where t is an integer from 0 to 12, t1 and t2 are each independent integers from 0 to 5, t3 and t4 are each independent integers of 1, and each R e R f Independently for C 1-15 Alkyl, C 2-15 alkenyl or C 2-15 alkynyl group; the C 5-30 Straight-chain hydrocarbon group, C 5-30 Each branched hydrocarbon group is independently substituted or unsubstituted, and the substitution is preferably C. 1-6 Alkyl, halogen or hydroxyl substitution. In one embodiment of this application, the C 5-30 The straight-chain hydrocarbon group is C 5-30 straight-chain alkyl, C 5-30 Straight-chain alkenyl or C 5-30 Straight-chain alkynyl group; more preferably C 5-25 Straight-chain hydrocarbon group, more preferably C 5-17 Straight-chain hydrocarbon group. In one embodiment of this application, each of the aforementioned R is more preferred. e R f Independently for C 1-15 Alkyl, C 2-15 alkenyl or C 2-15 alkynyl group; R e R f More preferably, each is independently selected from any one of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, vinyl, propenyl, pentenyl, hexenyl, heptenyl, octenyl, nonenyl, decenyl, ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptenyl, octenyl, nonynyl, and decynyl; R e R f More preferably, each is independently selected from any one of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, and decyl. In one embodiment of this application, R1 and R2 are any one of the following: Case (1): R1 and R2 are each independently C 5-30 Straight-chain hydrocarbon groups; Case (2): Either R1 or R2 is chosen as C. 5-30 The other is a straight-chain hydrocarbon group, and the other is C. 5-30 Branched hydrocarbon group Case (3): R1 and R2 are each independently C 5-30 Branched hydrocarbon group Case (4): R1 and R2 are each independent of each other. Case (5): Either R1 or R2 is chosen as C. 5-30 Straight-chain hydrocarbon group or C 5-30 Branched hydrocarbon group Another one is Case (6): Either R1 or R2 is chosen as The other is C 5-30 Straight-chain hydrocarbon group, C 5-30 Branched hydrocarbon group Case (7): R1 and R2 are each independent of each other. In one embodiment of this application, R1 and R2 that satisfy the above conditions are further preferably, C 5-30 The straight-chain hydrocarbon group is selected from any of the following structures: Preferably, the C 5-30 The branched hydrocarbon group is selected from any of the following structures: Preferably, the Choose from any of the following structures: Preferably, the Choose from any of the following structures: Furthermore, it is preferable that t in R1 and R2 mentioned above is 0, 1 or 2. 1.3.R In this application, R is C 5-30 Hydrocarbon group or C-aryl group interrupted by ester bond 5-30 hydrocarbon group, represented as Among them, B R It is any one of propylidene, butylidene, pentylidene, hexylidene, heptaylidene, and octylidene; L R For connecting key, -C(=O)O- or -OC(=O)-; R R For linear or branched C 5-18 Hydrocarbon group. In one embodiment of this application, the... Preferably, any one of the following structures is selected: 1.4. L3, L4 In this application, each L3 and L4 is independently any one of -C(=O)-, -C(=O)O-, -OC(=O)-, -OC(=O)O-, -NHC(=O)O-, and -NHC(=O)-; each B1 and B2 is independently any one of butylene, pentylene, hexylene, heptylene, and octylene. 1.5. Excerpt In one embodiment of this application, each of the above is preferred. Independently, it can be any of the following structures: 1.6. Combination of Variables In one embodiment of this application, the definitions of the variables involved in the various general formulas in section 1. are independent of each other. Any definition of these variables can be combined with each other in any way; that is, the definitions of any variable can be combined with the definitions of any other one or more variables to form different embodiments of this application. For example, any two or more of the following variables can be combined: N in section 1.1. g R1 and R2 in section 1.2, R in section 1.3, L3 and L4 in section 1.4, and L4 in section 1.5. The cationic lipid structures obtained after each combination scheme are shown in all the examples. 1.7. Examples of structural formulas In one embodiment of this application, When f is 0, L e When the carbon is -C (=O)-, the structural formula of the cationic lipid is (1-A); When f is 1, L e When the form is -CH(OH)-, the structure of the cationic lipid satisfies the corresponding formula (1-B); Preferably, the structure of the cationic lipid satisfies formulas (2-1)-(2-4): More preferably, the structure of the cationic lipid satisfies any one of the following general formulas: Preferably, B1 and B2 are each independently selected from butylene, pentylene, hexylene, heptylene, and octylene; R is C 5-30Hydrocarbon group or C-aryl group interrupted by ester bond 5-30 hydrocarbon group, represented as Among them, B R It is any one of propylidene, butylidene, pentylidene, hexylidene, heptaylidene, and octylidene; L R For connecting key, -C(=O)O- or -OC(=O)-; R R For linear or branched C 5-18 Hydrocarbon group. 1.8. Examples of specific structures In one embodiment of this application, the structure of the cationic lipid is preferably selected from any of the following structures: Alternatively, the structure of the cationic lipid may be any of the following: 2. Preparation of cationic lipids 2.1. In one embodiment of this application, the preparation process of the cationic lipid represented by formula (1) is as follows: The intermediates / raw materials involved in the preparation process of the cationic lipids in this application include, but are not limited to, CORE0, IM-FL, Nr0, CORE0-(Tail)2, Nr-(Tail)2, Nr-CORE0, IM-EPO, and Nr-OH. The preparation process of the cationic lipids of this application may involve amino acids or their derivatives COREO, wherein COREO contains one protected or unprotected -NH2 and two protected or unprotected -COOH groups. In one embodiment of this application, CORE0 is selected from any of the following structures: When COREO contains protected amino or carboxyl groups, it must undergo deprotection treatment before participating in the reaction. The preparation process of the cationic lipid in this application may involve a linear intermediate IM-FL containing one functional group, with the structure represented as F3-B1- L3-R1, F4-B2-L4-R2, wherein functional groups F3 and F4 are groups that can react with the carboxyl group in CORE0, selected from -OH or -NH2, and the definitions of the other symbols are consistent with those in formula (1). IM-FL can be prepared by any suitable chemical reaction, including single-step or stepwise reactions such as esterification, amidation, alkylation, addition, or substitution. For example, in Example 1.1, S1-1 The hydroxyl group, after being protected by TBS, reacts with S1-3 Esterification followed by removal of the TBS protecting group yields the small molecule intermediate S1-4. Corresponding small molecule intermediate IM-FL). In one embodiment of this application, IM-FL is selected from any of the following structures: The preparation process of the cationic lipids in this application involves a small molecule intermediate Nr0 containing a tertiary amine moiety, the structure of which is represented as follows: The Nr0 contains one reactive group F. q Among them, F q The group that can react with -NH2 in CORE0 is selected from -Br, -CHO, and -CH=CH-, and the definitions of the other symbols are consistent with those in formula (1). Nr0 can be prepared by any suitable chemical reaction, including single-step or stepwise reactions such as esterification, amidation, alkylation, addition, or substitution. For example, in Example 1.2, S1-10 With S1-11 The substitution reaction yields the small molecule intermediate S1-12 ( Corresponding to the small molecule intermediate Nr0). In one embodiment of this application, Nr0 is selected from any of the following structures: The preparation of the cationic lipids in this application may involve an intermediate COREO-(Tail)2 containing -NH2 and two linear or branched hydrophobic tails, structurally represented as follows: The definitions of the other symbols are consistent with those in equation (1). CORE0-(Tail)2 can be obtained by performing a single or multiple identical or different reactions between IM-FL and CORE0. For example, S1-4 in Example 1.1 ( Corresponding to IM-FL) and S1-5 ( The corresponding CORE0) undergoes esterification, followed by removal of the Boc protecting group to obtain S1-6 ( Corresponding to CORE0-(Tail)2). In one embodiment of this application, CORE0-(Tail)2 is selected from any of the following structures: The preparation process of the cationic lipid in this application involves an intermediate Nr-(Tail)2 containing a tertiary amine moiety, a secondary amine moiety, and four hydrophobic tails, with the structure represented as follows: The definitions of the other symbols are consistent with those in equation (1). Nr-(Tail)2 can be obtained by performing single or multiple identical or different reactions between Nr0 and CORE0-(Tail)2. For example, in Example 1.1, S1-7 ( Corresponding to Nr0) and S1-6 ( The substitution reaction of CORE0-(Tail)2 yields S1-8 ( Corresponding to Nr-(Tail)2). In one embodiment of this application, Nr-(Tail)2 is selected from any of the following structures: The preparation process of the cationic lipid in this application involves an intermediate Nr-CORE0 containing a tertiary amine moiety, a secondary amine moiety, and two carboxyl groups, with the structure represented as follows: The definitions of the other symbols are consistent with those in equation (1). Nr-CORE0 can be obtained by a single-step or multi-step reaction between Nr0 and CORE0. In one embodiment of this application, Nr-CORE0 is selected from any of the following structures: The preparation process of the cationic lipids in this application may involve a substituted or unsubstituted reactive group F. c The hydrophobic hydrocarbon tail chain IM-EPO, structurally represented as The F c -COOH, -C(=O)Cl, Any one of them, and the definitions of the other symbols are consistent with those in formula (1). IM-EPO can be obtained by purchase or prepared by any suitable chemical reaction, including single-step or stepwise reactions such as esterification, amidation, alkylation, addition, or substitution. For example, in Example 5, S5-1 With S5-2 S5-4 can be obtained through esterification followed by epoxidation. (Corresponding to IM-EPO). In one embodiment of this application, the IM-EPO is selected from any of the following structures: The preparation of the cationic lipids in this application may involve an Nr-OH containing a hydrophobic tail, wherein the Nr-OH also contains a tertiary amine moiety and an amino acid or its derivative COREO, the structure of which is represented as follows: The definitions of each symbol are consistent with those in equation (1). Nr-OH is obtained by a single-step or stepwise reaction of Nr-COREO containing a tertiary amine moiety with IM-EPO. In one embodiment of this application, Nr-OH is selected from any of the following structures: In one embodiment of this application, the cationic lipid can be prepared by any of the following methods: Method (1): React any of the aforementioned CORE0 with two identical or different IM-FLs to obtain CORE0-(Tail)2, then react CORE0-(Tail)2 with Nr0 to obtain Nr-(Tail)2, and then react Nr-(Tail)2 with IM-EPO in a single step or stepwise reaction to obtain the target product; Method (2): React any of the aforementioned CORE0 with any of the Nr0 to obtain Nr-CORE0. Then, Nr-CORE0 reacts with two identical or different IM-FLs in a single step or stepwise reaction to obtain Nr-(Tail)2. Then, Nr-(Tail)2 reacts with IM-EPO in a single step or stepwise reaction to obtain the target product. Method (3): React any of the aforementioned Nr-CORE0 with any of the IM-EPO to obtain Nr-OH, and then react with two identical or different IM-FLs in a single step or stepwise reaction to obtain the target product. Nr-CORE0 is obtained by reacting Nr0 with any of the CORE0. 2.2. Description of relevant raw materials and / or steps in the preparation process 2.2.1. Condensing agents, oxidizing agents, reducing agents In this application, the condensing agent used in the reaction is not limited, but N,N'-diisopropylcarbodiimide (DIC), N,N'-dicyclohexylcarbonyldiimide (DCC), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl, EDCI), 2-(7-azobenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate (HATU), benzotriazole-N,N,N',N'-tetramethylurea hexafluorophosphate (HBTU), and most preferably DCC. A suitable catalyst (such as 4-dimethylaminopyridine) can be added to this reaction. In this application, there are no particular limitations on the oxidant used in the reaction, as long as it is a compound or combination of compounds that can increase the oxidation state of the substrate. Preferred oxidants include phenyl iodide di(trifluoroacetate), 1,4-benzoquinone, benzyltrimethylammonium tribromide, pyridinium dichromate, potassium dichromate, ozone, oxygen, hypofluoride, sodium hypochlorite, cobalt acetate, cobalt acetate, manganese acetate, palladium acetate, copper acetate, monoperoxyphthalic acid, iodine, N-iodosuccinimide, iodobenzoic acid, 2-iodobenzoic acid, dimethyl dioxane, dimethyl sulfoxide-oxalyl chloride, dimethyl sulfoxide-acetic anhydride, DDQ, ruthenium dichlorotris(triphenylphosphine)dioxide, manganese dioxide, diacetoxyiodobenzoin, periodic acid, sodium periodate, sodium periodate-osmium tetroxide, and permanganate. Potassium, sodium perborate, peroxybenzoic acid, benzoyl peroxide, nickel peroxide, hydrogen peroxide, cumene hydroperoxide, tert-butanol peroxide, peracetic acid, m-chloroperoxybenzoic acid, N-chlorosuccinimide, pyridine chlorochromate, palladium chloride-copper chloride, urea-hydrogen peroxide complex, triphenylmethyltetrafluoroborate, tributyltin oxide, cobalt trifluoride, vanadium trifluorooxyfluoride, chromium trioxide, manganese triacetate, TEMPO, cerium ammonium nitrate, bromine, N-pyridine oxide, silver oxide, O-ethylperoxycarbonate, manganese acetylacetone, vanadium acetylacetone, aluminum isopropoxide, potassium peroxymonosulfate, dichloroiodobenzene, etc., or combinations thereof, more preferably oxygen, sodium hypochlorite, hydrogen peroxide, dichloroiodobenzene, potassium peroxymonosulfate, etc., or combinations thereof. In this application, there are no particular limitations on the reducing agent used in the reaction, as long as it can reduce the Schiff base formed by ammonia and aldehyde or ketone to an amino group; preferably, one or a combination of sodium borohydride, sodium cyanoborohydride, lithium aluminum hydride, borane, diborane, diisobutylaluminum hydride, diisopineborneol borane, lithium borohydride, zinc borohydride, borane-pyridine, borane-methyl sulfide, borane-tetrahydrofuran, etc.; more preferably, sodium cyanoborohydride. In this application, the solvent for the reaction can be a solvent-free solvent or an aprotic solvent. The aprotic solvent includes toluene, benzene, xylene, acetonitrile, ethyl acetate, diethyl ether, methyl tert-butyl ether, tetrahydrofuran, chloroform, dichloromethane, dimethyl sulfoxide, dimethylformamide, or dimethylacetamide, preferably tetrahydrofuran, dichloromethane, dimethyl sulfoxide, or dimethylformamide. In this application, 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); triethylamine and pyridine are preferred. 2.2.2. The reaction process involves the "protection" and "deprotection" of relevant functional groups. In this application, the reaction process involves the "protection" and "deprotection" of relevant functional groups. To prevent the functional group from affecting the reaction, it is typically protected. Furthermore, when there are two or more functional groups, only the target functional group is selectively reacted, thus protecting the other functional groups. Protecting groups not only stably protect the target functional group but also need to be easily removed as needed. Therefore, in organic synthesis, it is important to deprotect only the protecting groups bonded to the specified functional group under appropriate conditions. In this application, the definitions of "carboxyl protecting group" and "amino protecting group" are consistent with those in the "Terminology Explanation" section, and will not be repeated here. In this application, the hydroxyl group protected by the hydroxyl protecting group is not particularly limited, and can be, for example, an alcohol hydroxyl group, a phenolic hydroxyl group, etc. The amino group protected by the amino protecting group is not particularly limited, and can be, for example, derived from primary amines, secondary amines, hydrazines, amides, etc. The amino group in this application is not particularly limited, and includes, but is not limited to, primary amino groups, secondary amino groups, tertiary amino groups, and quaternary ammonium ions. In this application, the deprotection of the protected hydroxyl group is related to the type of hydroxyl protecting group. There is no particular limitation on the type of hydroxyl protecting group; taking benzyl, silyl ether, and tert-butyl groups for protecting terminal hydroxyl groups as examples, the corresponding deprotection methods include: A: Deprotection of the benzyl protecting group Benzyl deprotection can be achieved by hydrogenation of a hydrogen 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, but palladium and nickel are preferred. The support 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 protected hydroxyl compound, preferably 1 to 20 wt% of the protected hydroxyl compound. The reaction solvent is not particularly limited, as long as it can dissolve both the raw materials and the product, but 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, and ammonium formate are preferred. The reaction temperature is preferably 25 to 40°C. The reaction time is not particularly limited, but it is negatively correlated with the amount of catalyst used, and is preferably 1 to 5 hours. B: Deprotection of the silyl ether protecting group Compounds used for this type of hydroxyl protection include trimethylsilyl ether, triethylsilyl ether, dimethyl tert-butylsilyl ether, and tert-butyldiphenylsilyl ether. Deprotection of these silyl ethers is achieved using fluoride-containing compounds, preferably tetrabutylammonium fluoride, tetraethylammonium fluoride, hydrofluoric acid, and potassium fluoride, more preferably tetrabutylammonium fluoride and potassium fluoride. The amount of fluoride-containing reagent is 5 to 20 times the molar equivalent of the protected hydroxyl group, preferably 8 to 15 times the initiator. If the amount of fluoride is less than 5 times the molar equivalent of the protected hydroxyl group, incomplete deprotection will occur; if the amount of deprotecting reagent is greater than 20 times the molar equivalent of the protected hydroxyl group, excess reagent or compound will cause purification problems, may be introduced into subsequent steps, and thus cause side reactions. There are no particular restrictions on the reaction solvent, as long as it can dissolve the reactants and products. Aprotic solvents are preferred, more preferably tetrahydrofuran and dichloromethane. The reaction temperature is preferably 0 to 30°C. When the temperature is below 0°C, the reaction rate is slow and the protecting group cannot be completely removed. C: Deprotection of the tert-butyl protecting group The deprotection of the tert-butyl group is carried out under acidic conditions, preferably with a solution pH of 0 to 4. The acid is not particularly limited, but acetic acid, phosphoric acid, sulfuric acid, hydrochloric acid, and nitric acid are preferred, with hydrochloric acid being more preferred. The reaction solvent is not particularly limited, as long as it can dissolve both the reactants and products; water is preferred. The reaction temperature is preferably 0 to 30°C. 2.2.3. Alkylation reaction The alkylation reaction in this application is preferably based on the alkylation of hydroxyl, mercapto, or amino groups, corresponding sequentially to the formation of ether bonds, thioether bonds, secondary amino groups, or tertiary amino groups. Examples are as follows: 2.2.3.1. Alkylation of substrate alcohols with sulfonates and halogenated derivatives In the presence of a base, an ether intermediate is obtained by nucleophilic substitution of the substrate alcohol with a sulfonate derivative and a halide. The molar equivalents of the sulfonate and halide are 1 to 50 times that of the substrate alcohol, preferably 1 to 5 times. When the molar equivalents of the sulfonate and halide are less than one molar equivalent of the substrate alcohol, the substitution reaction is incomplete, making purification difficult. Conversely, when the molar equivalents of the sulfonate and halide are greater than 50 times that of the substrate alcohol, excess reagents complicate purification, potentially contaminating subsequent steps and increasing the likelihood of side reactions, thus further complicating purification. The resulting product is a mixture of an ether intermediate and excess sulfonate and halogenated derivatives, which can be purified by anion exchange resin, permeation, ultrafiltration, etc. The anion exchange resin is not particularly limited, as long as the target product can undergo ion exchange and adsorption on the resin. Preferably, it is an ion exchange resin with tertiary amines or quaternary ammonium salts as the backbone, such as dextran, agarose, polypropylene ester, polystyrene, or polystyrene. The solvents for permeation and ultrafiltration are not limited; generally, water or organic solvents are acceptable. The organic solvent is not particularly limited, as long as the product can dissolve in it. Preferred solvents include dichloromethane and trichloromethane. The reaction solvent is not limited, but aprotic solvents are preferred, such as toluene, benzene, xylene, acetonitrile, ethyl acetate, tetrahydrofuran, chloroform, dichloromethane, dimethyl sulfoxide, dimethylformamide or dimethylacetamide, and more preferably dimethylformamide, dichloromethane, dimethyl sulfoxide or tetrahydrofuran. The base includes organic bases (such as triethylamine, pyridine, 4-dimethylaminopyridine, imidazole, or diisopropylethylamine) or inorganic bases (such as sodium carbonate, sodium hydroxide, sodium bicarbonate, sodium acetate, potassium carbonate, or potassium hydroxide), preferably organic bases, and more preferably triethylamine or pyridine. The molar amount of the base is 1 to 50 times the molar equivalent of the sulfonate or halogenated product, preferably 1 to 10 times. 2.2.3.2. Alkylation of substrate amines with sulfonates and halogenated derivatives A. Alkylation of the substrate amine with sulfonates and halogens In the presence of a base, an amine intermediate is obtained by nucleophilic substitution of the substrate amine with a sulfonate derivative and a halide. The molar equivalent of the sulfonate and halide is 1 to 50 times that of the substrate amine, preferably 1 to 5 times. When the molar equivalent of the sulfonate and halide is less than one molar equivalent of the substrate amine, the substitution reaction is incomplete, making purification difficult. Conversely, when the molar equivalent of the sulfonate and halide is greater than 50 times that of the substrate amine, excess reagents complicate purification, potentially contaminating subsequent steps and increasing the likelihood of side reactions, thus further complicating purification. The resulting product is a mixture of amine intermediates and excess sulfonates and halogenated derivatives, which can be purified by column chromatography, anion exchange resins, permeation, and ultrafiltration. The anion exchange resin is not particularly limited, as long as the target product can undergo ion exchange and adsorption on the resin. Preferably, it is an ion exchange resin with tertiary amines or quaternary ammonium salts as the backbone, such as dextran, agarose, polypropylene ester, polystyrene, or polystyrene. The solvents for permeation and ultrafiltration are not limited; generally, water or organic solvents are acceptable. The organic solvent is not particularly limited, as long as the product can dissolve in it. Preferred solvents include dichloromethane and trichloromethane. The reaction solvent is not limited, but aprotic solvents are preferred, such as toluene, benzene, xylene, acetonitrile, ethyl acetate, tetrahydrofuran, chloroform, dichloromethane, dimethyl sulfoxide, dimethylformamide or dimethylacetamide, and more preferably dimethylformamide, dichloromethane, dimethyl sulfoxide or tetrahydrofuran. The base includes organic bases (such as triethylamine, pyridine, 4-dimethylaminopyridine, imidazole, or diisopropylethylamine) or inorganic bases (such as sodium carbonate, sodium hydroxide, sodium bicarbonate, sodium acetate, potassium carbonate, or potassium hydroxide), preferably organic bases, and more preferably triethylamine or pyridine. 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 amines with aldehyde derivatives The reaction of a substrate amine with an aldehyde derivative yields an imine intermediate, which is then reacted with a reducing agent to obtain an amine intermediate. The molar equivalent of the aldehyde derivative is 1 to 20 times that of the substrate amine, preferably 1 to 2 times, and more preferably 1 to 1.5 times. When the molar equivalent of the aldehyde derivative is greater than 20 times that of the substrate amine, excess reagent complicates purification, potentially contaminating subsequent steps and increasing purification difficulty. When the molar equivalent of the aldehyde derivative is less than 1 times that of the substrate amine, the reaction is incomplete, further increasing purification difficulty. The product after the reaction can be purified using cation exchange resins, permeation, ultrafiltration, etc. The cation exchange resin is not particularly limited, as long as it can exchange with quaternary ammonium cations to achieve separation. The solvents for permeation and ultrafiltration are not limited; generally, water or organic solvents are acceptable. The organic solvent is not particularly limited, as long as the product can dissolve in it; dichloromethane and trichloromethane are preferred. The reaction solvent is not limited, but organic solvents are preferred, such as methanol, ethanol, water, toluene, benzene, xylene, acetonitrile, ethyl acetate, tetrahydrofuran, chloroform, dichloromethane, dimethyl sulfoxide, dimethylformamide, or dimethylacetamide; water and methanol are more preferred. There are no particular limitations on the reducing agent, as long as it can reduce imine to amine. Sodium borohydride, lithium aluminum hydride, sodium cyanoborohydride, Zn / AcOH, etc. are preferred, with sodium cyanoborohydride being more preferred. Generally, the amount of reducing agent used is 0.5 to 50 times the amount of the aldehyde derivative, more preferably 1 to 10 times. 3. Lipid composition In this application, a lipid composition is provided, comprising a cationic lipid represented by formula (1). In one embodiment of this application, the lipid composition contains a cationic lipid represented by formula (1), and further contains one or more of phospholipids, steroid lipids, polyethylene glycol lipids, another cationic lipid, and anionic lipids; preferably, the lipid composition further contains any one of phospholipids, steroid lipids, and polyethylene glycol lipids; more preferably, the lipid composition further contains any two of phospholipids, steroid lipids, and polyethylene glycol lipids; even more preferably, the lipid composition further contains phospholipids, steroid lipids, and polyethylene glycol lipids; most preferably, the lipid composition further contains phospholipids, steroid lipids, polyethylene glycol lipids, and another cationic lipid; or the lipid composition further contains phospholipids, steroid lipids, polyethylene glycol lipids, and anionic lipids. The aforementioned lipid composition includes the following cases: the lipid composition; Case (1): The lipid composition further contains phospholipids; or, Case (2): The lipid composition further contains steroid lipids; or, Case (3): The lipid composition further contains polyethylene glycol lipids; or, Case (4): The lipid composition further contains phospholipids and steroid lipids; or, Case (5): The lipid composition further contains phospholipids and polyethylene glycol lipids; or, Case (6): The lipid composition further contains steroid lipids and polyethylene glycol lipids; or, Case (7): The lipid composition further contains phospholipids, steroid lipids, and polyethylene glycol lipids; or, Case (8): The lipid composition further contains phospholipids, steroid lipids, polyethylene glycol lipids, and another cationic lipid; or, Case (9): The lipid composition further contains phospholipids, steroid lipids, polyethylene glycol lipids and anionic lipids. In one embodiment of this application, the phospholipids in the lipid composition are preferably 1,2-dilinoleoyl-sn-glycerol-3-phosphocholine (DLPC), 1,2-dimyristoyl-sn-glycerol-3-phosphocholine (DMPC), 1,2-dioleoyl-sn-glycerol-3-phosphocholine (DOPC), 1,2-dipalmitoyl-sn-glycerol-3-phosphocholine (DPPC), 1,2-distearateoyl-sn-glycerol-3-phosphocholine (DSPC), 1,2-diundecanoyl-sn-glycerol-3-phosphocholine (DUPC), 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (POPC), or 1,2-di-O-octadecenyl-sn-glycerol-3-phosphocholine (18:0Diether). 1,2-Dilinoleoyl-sn-glycerol-3-phosphate choline (OChemsPC), 1-hexadecyl-sn-glycerol-3-phosphate choline (C16 Lyso PC), 1,2-dilinoleoyl-sn-glycerol-3-phosphate choline, 1,2-disarachidonicoyl-sn-glycerol-3-phosphate choline, 1,2-bis(docohexanoyl-sn-glycerol-3-phosphate choline), 1,2-dioleoyl-sn-glycerol-3-phosphate ethanolamine (DOPE), 1,2-diphydanyl-sn-glycerol-3-phosphate ethanolamine (ME) 16.0PE), 1,2-distearate-sn-glycerol-3-phosphate ethanolamine, 1,2-dilinoleoyl-sn-glycerol-3-phosphate ethanolamine, 1,2-dilinoleoyl-sn-glycerol-3-phosphate ethanolamine, 1,2-diarachidonicoyl-sn-glycerol-3-phosphate ethanolamine, 1,2-bis(docosahexaenooyl-sn-glycerol-3-phosphate ethanolamine), 1,2-dioleoyl-sn-glycerol-3-phosphate-rac-(1-glycerol) sodium salt (DOPG), dioleoylphosphatidylserine The following are any one of the following: (DOPS), dipalmitoylphosphatidylglycerol (DPPG), palmitoyloleoylphosphatidylethanolamine (POPE), distearate-phosphatidyl-ethanolamine (DSPE), dipalmitoylphosphatidylethanolamine (DPPE), dimyristoylphosphatidylethanolamine (DMPE), 1-stearoyl-2-oleoylphosphatidylcholine (SOPC), sphingomyelin, phosphatidylinositol, phosphatidic acid, palmitoyloleoylphosphatidylcholine, lysophosphatidylcholine and lysophosphatidylethanolamine (LPE) and combinations thereof. In one embodiment of this application, the steroid lipids in the lipid composition are preferably any one of cholesterol, coprosterol, sitosterol, ergosterol, campesterol, stigmasterol, rapeseed sterol, tomatine, ursolic acid, and α-tocopherol, or combinations thereof. In one embodiment of this application, the polyethylene glycol lipid in the lipid composition is preferably polyethylene glycol-1,2-dimyristoyl glyceride (PEG-DMG), polyethylene glycol-distearyl phosphatidylethanolamine (PEG-DSPE), PEG-cholesterol, polyethylene glycol-diacylglycerol (PEG-DAG), polyethylene glycol-dialkoxypropyl (PEG-DAA), specifically including any one of polyethylene glycol 500-dispalmitoylphosphatidylcholine, polyethylene glycol 2000-dispalmitoylphosphatidylcholine, polyethylene glycol 500-distearyl phosphatidylethanolamine, polyethylene glycol 2000-distearyl phosphatidylethanolamine, polyethylene glycol 500-1,2-dioleoylphosphatidylethanolamine, polyethylene glycol 2000-1,2-dioleoylphosphatidylethanolamine and polyethylene glycol 2000-2,3-dimyristoyl glycerol (PEG-DMG) and combinations thereof. In one embodiment of this application, the polyethylene glycol lipid in the lipid composition is preferably any one of the following structures and combinations thereof: Wherein, n1 is an integer between 25 and 300, and more preferably n1 is any one of 44, 45, 46, 47, and 48. In one embodiment of this application, another cationic lipid in the lipid composition is selected from 1,2-dioleoyl-3-trimethylammonium-propane (methyl sulfate) (DOTAP), 1,2-bis(octadecyloxy-3-methylammonium-propane) chloride (DOTMA), 1-[2-(oleoyloxy)ethyl]-2-oleo-3-(2-hydroxyethyl)imidazoline chloride (DOTIM), 1,2-dioleoyl-3-dimethylamino-propane (DODMA), 2,3- Di(tetradecanoyloxy)propyltrimethylazone chloride (DMTAP), bis(decyl)dimethylammonium chloride (DDAC), bis(decyl)dimethylammonium bromide (DDAB), N,N-dioleoyl-N,N-dimethylammonium chloride (DODAC), N-(4-carboxybenzyl)-N,N-dimethyl-2,3-bis(oleoyloxy)prop-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(dodecane-2-ol)(C12-200), methyl 4-(N,N-dimethylamino)butyrate (dilinyl) ester (DLin-MC3-DMA), 1,2-dimyristoyl-sn-glycerol-3-ethylphosphocholine (EP) C), any one of ((4-hydroxybutyl)azadiyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate) (ALC-0315), 8-[(2-hydroxyethyl)(6-oxo-6-(undecapoxy)hexyl)amino]octanoate (heptadecane-9-yl) ester (SM-102) and ((2-(2-hydroxyethoxy)ethyl)azadialkyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate) (DHA-1) and combinations thereof. In one embodiment of this application, the anionic lipid in the lipid composition is selected from any one of 1,2-dioleoyl-sn-glycerol-3-phosphate sodium salt (18:1PA), 1,2-dimyristoyl-sn-glycerol-3-phosphate sodium salt (14:0PA), bis(monooleoylglycerol)ammonium phosphate (18:1BMP), and cardiolipin (CL) and combinations thereof. In one embodiment of this application, the lipid comprises 20-80% cationic lipids of formula (1), 5-16% phospholipids, 25-55% steroid lipids and 0.5-10% polyethylene glycol lipids, wherein the percentages are the molar percentages of each lipid in the total lipids. In one embodiment of this application, the preferred lipid composition is that the cationic lipid accounts for 30-65% of the total lipid molar percentage; more preferably, it is any one of about 35%, 40%, 45%, 46%, 47%, 48%, 49%, 50%, and 55%. In one embodiment of this application, preferably, in any of the aforementioned lipid compositions, the phospholipids account for about 7.5-16% of the total lipids in molar percentage; more preferably, it is any one of about 8%, 9%, 10%, 11%, 12%, or 16%. In one embodiment of this application, preferably, in any of the aforementioned lipid compositions, the steroid lipids account for 35-50% of the total lipids in molar percentage, more preferably, about 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, or 50%. In one embodiment of this application, in any of the aforementioned lipid compositions, polyethylene glycol lipids account for 0.5-5% of the total lipids; more preferably 1-3%; and more preferably any one of about 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2.0%, and 2.5%. 4. Lipid-based pharmaceutical compositions In one embodiment of this application, a lipid pharmaceutical composition comprises any of the lipid compositions and pharmaceuticals described above, wherein the lipid composition comprises any of the cationic lipids with the structure shown in Formula (1) described above, and the pharmaceuticals are selected from any of the nucleic acid pharmaceuticals, gene vaccines, antitumor pharmaceuticals, small molecule pharmaceuticals, polypeptide pharmaceuticals or protein pharmaceuticals. In one embodiment of this application, the nucleic acid drug in the lipid drug composition is selected from any one of RNA, DNA, antisense nucleic acid, plasmid, interfering nucleic acid, aptamer, antagomir, and ribozyme, and the RNA is selected from any one of mRNA, saRNA, circRNA, miRNA, and siRNA; preferably, the nucleic acid drug is any one of DNA, mRNA, miRNA, and siRNA. In one embodiment of this application, the preferred lipid pharmaceutical composition is preferably used to prepare a drug, said drug being selected from any one of antitumor agents, antiviral agents, antifungal agents, and vaccines. In one embodiment of this application, the drugs in the lipid pharmaceutical 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, lactamase, mefenamic acid, carmustine, romustine, busulfan, dibromomannitol, mitomycin C, cisdichlorodiamine cycloplatin(II), methotrexate, 6-mercaptopurine, 6-thioguanine, cytarabine, 5-fluorouracil dacarbazine, debucaine, chlorpromazine, propranolol, dimorol, labetalol, clonidine, hydralazine, imipramine, amitriptyline, and more. The following medications are listed: chlorpheniramine, phenytoin, diphenhydramine, chlorpheniramine, promethazine, gentamicin, ciprofloxacin, cefoxitin, miconazole, terconazole, econazole, isoconazole, butonazole, clotrimazole, itraconazole, nystatin, neftifine, amphotericin B, antiparasitic agents, hormones, hormone antagonists, immunomodulators, neurotransmitter antagonists, antiglaucoma medications, vitamins, sedatives and imaging agents, paclitaxel, cytochalasin B, bacitracin D, ethidium bromide, emetine, mitomycin, etoposide, teniposide, colchicine, daunorubicin, dihydroxyanthraquinone, safflowerin, 1-dehydrotestosterone, glucocorticoids, procaine, tetracaine, lidocaine, puromycin, and serotonin. In one embodiment of this application, the N / P ratio of the lipid composition to the nucleic acid is preferably (0.1-100):1, more preferably (0.2-30):1, and most preferably (0.5-20):1. 5. Liposomes or lipid nanoparticles and their preparation 5.1. Liposomes or lipid nanoparticles In one embodiment of this application, a liposome or lipid nanoparticle contains any of the lipid pharmaceutical compositions described above. In one embodiment of this application, the aforementioned lipid nanoparticles are preferably LNP-drug compositions, LPP-drug compositions, or PNP-drug compositions; preferably LNP-drug compositions; more preferably LNP-nucleic acid drug compositions; and even more preferably LNP-mRNA drug compositions. 5.2. Preparation of liposomes or lipid nanoparticles In one embodiment of this application, liposomes can be prepared by methods including but not limited to thin film dispersion, ultrasonic dispersion, reverse phase evaporation, freeze drying, freeze-thaw, double emulsion, and injection, preferably thin film dispersion, ultrasonic dispersion, and / or reverse phase evaporation. In one embodiment of this application, lipid nanoparticles can be prepared by methods including, but not limited to, microemulsion, double emulsion, high-shear homogenization ultrasonication, thin film hydration extrusion, and microfluidic methods. In one embodiment of this application, liposomes are prepared using a thin-film dispersion method, which includes the following steps: (1) Weigh cationic lipids, steroid lipids, neutral lipids and polyethylene glycol lipids, 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, sonicate in water bath to form a semi-transparent emulsion; (3) The emulsion is added to a high-pressure homogenizer and then pressed. After pressing, the emulsion is added to a liposome extruder and passed through a membrane to form liposomes. (4) Optionally, the liposomes are dried in a freeze dryer to form liposome powder. In one embodiment of this application, in the method for preparing liposomes, 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, and more preferably 1 mg: (0.5-5) mL. In one embodiment of this application, lipid nanoparticles are preferably prepared using microfluidic, vortex, or simple mixing methods, as follows: (1) Dissolve each lipid component in an organic solvent to obtain a lipid composition soluble in an organic phase; the organic phase is preferably ethanol; (2) Add the nucleic acid drug to the buffer solution to obtain an aqueous solution; the aqueous phase is preferably citrate buffer or sodium acetate buffer. (3) The organic phase solution and the aqueous phase solution are mixed by microfluidic device, vortex or pipette to form a lipid nanoparticle composition, and purified by ultrafiltration to remove organic solvents and free nucleic acid molecules. 6. Lipid-based pharmaceutical composition formulations In one embodiment of this application, a lipid pharmaceutical composition formulation contains any of the lipid pharmaceutical compositions in any of the preceding 4. parts, any of the liposomes or lipid nanoparticles in any of the preceding 5. parts, and further contains a pharmaceutically acceptable diluent or excipient, wherein the diluent or excipient is preferably any one of deionized water, ultrapure water, phosphate buffer, and physiological saline, more preferably phosphate buffer or physiological saline, and most preferably physiological saline. The preparation methods described in this application include any protection and deprotection processes performed on specific groups as required by the reaction. The intermediates and final products prepared in this application can be purified by methods including, but not limited to, extraction, recrystallization, adsorption treatment, precipitation, reverse precipitation, thin-film dialysis, supercritical extraction, and column chromatography (including gel columns, ion columns, silica gel columns, etc.). Characterization of the structure, molecular weight, and purity of the intermediates and final products can be achieved using methods including, but not limited to, […]. 1Methods used included 1H NMR, electrophoresis, UV-Vis spectrophotometry, FTIR, AFM, GPC, HPLC, MALDI-TOF MS, and circular dichroism spectroscopy. In this application, the cationic lipid final product was characterized structurally by NMR and its molecular weight was confirmed by mass spectrometry; the polymer structure was confirmed by NMR, and the polymer molecular weight (default number-average molecular weight M) was determined. n The polydispersity index (PDI) was determined by gel permeation chromatography (GPC), and the degree of polymerization of the polymer (default number-average degree of polymerization) was calculated based on its molecular weight. The following specific embodiments further describe the preparation methods of cationic lipids, lipid compositions, lipid pharmaceutical compositions, lipid pharmaceutical composition formulations, and bioactivity testing of lipid pharmaceutical compositions. These specific embodiments are for further detailed explanation of this application and are not intended to limit the scope of protection of this application. Example 1: Preparation of cationic lipids E1-1, E1-2, E1-3 and E1-4 Example 1.1: Preparation of cationic lipid E1-1 The preparation process is as follows: Step a: Under nitrogen protection, tert-butyldimethylchlorosilane (2.49 g, 16.5 mmol) was added to a round-bottom flask containing 7-hydroxyheptanoic acid (S1-1, 2.19 g, 15.0 mmol) dissolved in DMF (70 mL) and imidazole (2.55 g, 37.5 mmol). The reaction solution was stirred overnight at 50 °C. After the reaction was completed, the mixture was cooled to room temperature, diluted with water, extracted three times with ethyl acetate, and the organic phases were combined, washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, concentrated, and purified by column chromatography to obtain S1-2 (3.56 g). Step b: Under nitrogen protection, N,N'-dicyclohexylcarbodiimide (DCC, 3.21 g, 15.6 mmol) was added to a round-bottom flask containing S1-2 (3.12 g, 12.0 mmol), 9-heptadecyl alcohol (S1-3, 3.69 g, 14.4 mmol), and 4-dimethylaminopyridine (DMAP, 0.37 g, 3.0 mmol) dissolved in dichloromethane (120 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 (30 mL), and then 30 mL of TBAF tetrahydrofuran solution (1 M) was added. The reaction was carried out overnight to remove TBS protection. After the reaction was completed, the mixture was concentrated and extracted. The organic phase was dried over anhydrous magnesium sulfate, filtered, concentrated, and the crude product was purified by column chromatography to obtain compound S1-4 (3.02 g). Step c: Under nitrogen protection, DCC (1.36 g, 6.6 mmol) was added to a round-bottom flask containing (tert-butyloxycarbonyl)glutamic acid (S1-5, 0.74 g, 3.0 mmol), S1-4 (2.89 g, 7.5 mmol), and DMAP (0.15 g, 1.2 mmol) dissolved in dichloromethane (50 mL). The reaction was carried out at room temperature for 16 h. After the reaction was completed, the precipitate was removed by filtration, and the reaction solution was concentrated to obtain the crude product. The crude product was then dissolved in dichloromethane, TFA was added to a final concentration of 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 organic phase was dried over anhydrous magnesium sulfate, filtered, concentrated, and purified by column chromatography to obtain S1-6 (2.01 g). Step d: Under nitrogen protection, compound S1-6 (1.32 g, 1.5 mmol) was dissolved in acetonitrile (20 mL). (3-bromopropyl)dimethylamine (S1-7, 0.37 g, 2.3 mmol) and DIPEA (0.39 g, 3.0 mmol) were added sequentially with slow stirring. The reaction mixture was stirred at room temperature for approximately 20 h. After the reaction was complete, the reaction solution was concentrated and dissolved in dichloromethane. The solution was then washed sequentially with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution. The organic phase was dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. Compound S1-8 (1.37 g) was purified by column chromatography. Step e: At room temperature, S1-8 (1.02 g, 1.0 mmol), triethylamine (0.51 g, 5.0 mmol), and DMAP (0.21 g, 1.7 mmol) were dissolved sequentially in toluene (20 mL). Then, a toluene solution of nonanoyl chloride (S1-9, 0.23 g, 1.3 mmol) was slowly added dropwise. After the addition was complete, the reaction mixture was stirred overnight at room temperature. After the reaction was complete, methanol (20 mL) was added to the reaction mixture to remove excess acyl chloride. The reaction mixture was concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E1-1 (0.87 g). 1H NMR(400MHz, CDCl3)δ:4.90-4.82(m,2H,-C(=O)OCH<),4.40-4.16(m,1H,>NCH<),4.05(t,4H,-C (=O)OCH2CH2CH2-),3.20-3.10(m,2H,(CH3)2NCH2CH2CH2-),2.50-2.33(m,4H;2H,>CHCH2CH2-;2 H,(CH3)2NCH2-),2.31-2.26(m,6H;4H,-CH2C(=O)OCH<;2H,>NC(=O)CH2-),2.21-1.98(m,8H;2H, >CHCH2CH2-;6H,(CH3)2N-),1.72-1.19(m,86H,-CH2CH2CH2-,-CH2CH3),0.90(t,15H,-CH2CH3). MS(ESI):m / z=1105.0([M+H] + ). Example 1.2: Preparation of cationic lipid E1-2 The preparation process is as follows: Step a: S1-10 (0.38 g, 5.0 mmol), 1,3-dibromopropane (S1-11, 1.52 g, 7.5 mmol), and sodium carbonate (Na2CO3, 0.27 g, 2.5 mmol) were dissolved sequentially in THF (20 mL) solution and refluxed at 70 °C for 12 h. After the reaction was completed, the reaction solution was cooled to room temperature, filtered, and the filtrate was concentrated. The residue was dissolved in 2N hydrochloric acid, washed twice with ethyl acetate (10 mL * 2), and the pH of the aqueous phase was adjusted to 10 with 2N NaOH solution. Then, it was extracted three times with ethyl acetate (10 mL * 3). The organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and concentrated to obtain S1-12 (0.92 g). Step b: Under nitrogen protection, compound S1-6 (1.32 g, 1.5 mmol) was dissolved in acetonitrile (20 mL). S1-12 (0.44 g, 2.3 mmol) and DIPEA (0.39 g, 3.0 mmol) were added sequentially with slow stirring. The reaction mixture was stirred at room temperature for approximately 20 h. After the reaction was complete, the reaction solution was concentrated and dissolved in dichloromethane. The solution was then washed sequentially with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution. The organic phase was dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. Compound S1-13 (1.36 g) was purified by column chromatography. Step c: At room temperature, S1-13 (1.00 g, 1.0 mmol), triethylamine (0.51 g, 5.0 mmol), and DMAP (0.21 g, 1.7 mmol) were dissolved sequentially in toluene (20 mL). Then, a toluene solution of S1-9 (0.23 g, 1.3 mmol) was slowly added dropwise. After the addition was complete, the reaction mixture was stirred overnight at room temperature. After the reaction was complete, methanol (20 mL) was added to the reaction mixture to remove excess acyl chloride. The reaction mixture was concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E1-2 (0.88 g). 1 H NMR(400MHz, CDCl3)δ:4.92-4.80(m,2H,-C(=O)OCH<),4.42-4.15(m,1H,>NCH<),4.07(t,4H,-C(=O)OCH2CH 2CH2-),3.54(t,2H,HOCH2CH2-),3.20-3.10(m,2H,(CH3)2NCH2CH2CH2-),2.50-2.34(m,6H;2H,>CHCH2CH2- ;2H,HOCH2CH2-;2H,HOCH2CH2N(CH3)CH2-),2.30-2.26(m,6H;4H,-CH2C(=O)OCH<;2H,>NC(=O)CH2-),2.20- 1.97(m,5H;2H,>CHCH2CH2-;3H,>NCH3),1.71-1.20(m,86H,-CH2CH2CH2-,-CH2CH3),0.89(t,15H,-CH2CH3). MS(ESI):m / z=1135.0([M+H] + ). Example 1.3: Preparation of cationic lipid E1-3 The preparation process is as follows: Step a: S1-14 (0.53 g, 5.0 mmol), S1-11 (1.52 g, 7.5 mmol), and Na2CO3 (0.27 g, 2.5 mmol) were dissolved sequentially in THF (20 mL) solution and refluxed at 70 °C for 12 h. After the reaction was completed, the reaction solution was cooled to room temperature, filtered, and the filtrate was concentrated. The residue was dissolved in 2N hydrochloric acid, washed twice with ethyl acetate (10 mL * 2), and the pH of the aqueous phase was adjusted to 10 with 2N NaOH solution. Then, it was extracted three times with ethyl acetate (10 mL * 3). The organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and concentrated to obtain S1-15 (1.06 g). Step b: Under nitrogen protection, compound S1-6 (1.32 g, 1.5 mmol) was dissolved in acetonitrile (20 mL). S1-15 (0.51 g, 2.3 mmol) and DIPEA (0.39 g, 3.0 mmol) were added sequentially with slow stirring. The reaction mixture was stirred at room temperature for approximately 20 h. After the reaction was complete, the reaction solution was concentrated and dissolved in dichloromethane. The solution was then washed sequentially with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution. The organic phase was dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. Compound S1-16 (1.41 g) was purified by column chromatography. Step c: At room temperature, S1-16 (1.03 g, 1.0 mmol), triethylamine (0.51 g, 5.0 mmol), and DMAP (0.21 g, 1.7 mmol) were dissolved sequentially in toluene (20 mL). Then, a toluene solution of S1-9 (0.23 g, 1.3 mmol) was slowly added dropwise. After the addition was complete, the reaction mixture was stirred overnight at room temperature. After the reaction was complete, methanol (20 mL) was added to the reaction mixture to remove excess acyl chloride. The reaction mixture was concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E1-3 (0.92 g). 1 H NMR(400MHz, CDCl3)δ:4.90-4.81(m,2H,-C(=O)OCH<),4.42-4.14(m,1H,>NCH<),4.05(t,4H,-C(=O)OC H2CH2CH2-),3.60(t,4H,HOCH2CH2-),3.20-3.10(m,2H,(CH3)2NCH2CH2CH2-),2.51-2.32(m,8H;2H,>CH CH2CH2-;4H,HOCH2CH2-;2H,(HOCH2CH2)2NCH2-),2.29-2.25(m,6H;4H,-CH2C(=O)OCH<;2H,>NC(=O)CH2 -),2.20-1.98(m,2H,>CHCH2CH2-),1.72-1.18(m,86H,-CH2CH2CH2-,-CH2CH3),0.88(t,15H,-CH2CH3). MS(ESI):m / z=1165.0([M+H] + ). Example 1.4: Preparation of cationic lipid E1-4 The preparation process is as follows: Step a: S1-17 (0.53 g, 5.0 mmol), S1-11 (1.52 g, 7.5 mmol), and Na2CO3 (0.27 g, 2.5 mmol) were dissolved sequentially in THF (20 mL) solution and refluxed at 70 °C for 12 h. After the reaction was completed, the reaction solution was cooled to room temperature, filtered, and the filtrate was concentrated. The residue was dissolved in 2N hydrochloric acid, washed twice with ethyl acetate (10 mL * 2), and the pH of the aqueous phase was adjusted to 10 with 2N NaOH solution. Then, it was extracted three times with ethyl acetate (10 mL * 3). The organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and concentrated to obtain S1-18 (0.96 g). Step b: Under nitrogen protection, compound S1-6 (1.32 g, 1.5 mmol) was dissolved in acetonitrile (20 mL). S1-18 (0.46 g, 2.3 mmol) and DIPEA (0.39 g, 3.0 mmol) were added sequentially with slow stirring. The reaction mixture was stirred at room temperature for approximately 20 h. After the reaction was complete, the reaction solution was concentrated and dissolved in dichloromethane. The solution was then washed sequentially with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution. The organic phase was dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. Compound S1-19 (1.37 g) was purified by column chromatography. Step c: At room temperature, S1-19 (1.00 g, 1.0 mmol), triethylamine (0.51 g, 5.0 mmol), and DMAP (0.21 g, 1.7 mmol) were dissolved sequentially in toluene (20 mL). Then, a toluene solution of S1-9 (0.23 g, 1.3 mmol) was slowly added dropwise. After the addition was complete, the reaction mixture was stirred overnight at room temperature. After the reaction was complete, methanol (20 mL) was added to the reaction mixture to remove excess acyl chloride. The reaction mixture was concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E1-4 (0.91 g). 1H NMR(400MHz, CDCl3)δ:4.92-4.83(m,2H,-C(=O)OCH<),4.43-4.15(m,1H,>NCH<),4.04(t,4H,- C(=O)OCH2CH2CH2-),3.20-3.10(m,2H,MEP-CH2CH2CH2-),2.50-2.33(m,2H,>CHCH2CH2-),2.29 -2.26(m,6H;4H,-CH2C(=O)OCH<;2H,>NC(=O)CH2-),2.22-2.14(m,8H;4H,-N(CH2CH2)2-;2H,M EP-CH2-;2H,>CHCH2CH2-),1.73-1.22(m,92H,-CH2CH2CH2-,-CH2CH3),0.87(t,15H,-CH2CH3). MS(ESI):m / z=1145.0([M+H] + ). Example 2: Preparation of cationic lipid E2-1 The preparation process is as follows: Step a: Under nitrogen protection, 2-hexylundecanoic acid (S2-2, 2.56 g, 10.0 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 2.88 g, 15.0 mmol), 1,6-hexanediol (S2-1, 5.90 g, 50 mmol), DMAP (0.61 g, 5.0 mmol), and DIPEA (2.58 g, 20.0 mmol) were sequentially dissolved in dichloromethane (150 mL), and the reaction mixture was stirred at room temperature for 18 h. After the reaction was complete, the reaction mixture was washed with saturated sodium bicarbonate aqueous solution, the organic phase was separated and washed with brine, dried over anhydrous magnesium sulfate, filtered, concentrated, and the residue was purified by column chromatography to obtain S2-3 (3.21 g). Step b: Under nitrogen protection, DCC (1.36 g, 6.6 mmol) was added to a round-bottom flask containing S1-5 (0.74 g, 3.0 mmol), S2-3 (2.80 g, 7.5 mmol), and DMAP (0.15 g, 1.2 mmol) dissolved in dichloromethane (50 mL). The reaction was carried out at room temperature for 16 h. After the reaction was completed, the precipitate was removed by filtration, and the reaction solution was concentrated to obtain the crude product. The crude product was then dissolved in dichloromethane, TFA was added to a final concentration of 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 organic phase was dried over anhydrous magnesium sulfate, filtered, concentrated, and purified by column chromatography to obtain S2-4 (1.91 g). Step c: Under nitrogen protection, compound S2-4 (1.24 g, 1.5 mmol) was dissolved in acetonitrile (20 mL). S1-7 (0.37 g, 2.3 mmol) and DIPEA (0.39 g, 3.0 mmol) were added sequentially with slow stirring. The reaction mixture was stirred at room temperature for approximately 20 h. After the reaction was complete, the reaction solution was concentrated and dissolved in dichloromethane. The solution was then washed sequentially with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution. The organic phase was dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. Compound S2-5 (1.24 g) was purified by column chromatography. Step d: At room temperature, S2-5 (0.91 g, 1.0 mmol), triethylamine (0.51 g, 5.0 mmol), and DMAP (0.21 g, 1.7 mmol) were dissolved sequentially in toluene (20 mL). Then, a toluene solution of S1-9 (0.23 g, 1.3 mmol) was slowly added dropwise. After the addition was complete, the reaction mixture was stirred overnight at room temperature. After the reaction was complete, methanol (20 mL) was added to the reaction mixture to remove excess acyl chloride. The reaction mixture was concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E2-1 (0.83 g). 1 H NMR(400MHz, CDCl3)δ:4.41-4.15(m,1H,>NCH<),4.06(t,8H,-C(=O)OCH2CH2CH2-),3.20 -3.10(m,2H,(CH3)2NCH2CH2CH2-),2.52-2.33(m,4H;2H,>CHCH2CH2-;2H,(CH3)2NCH2-) ,2.31-2.26(m,4H;2H,-CH2OC(=O)CH<;2H,>NC(=O)CH2-),2.21-1.99(m,8H;2H,>CHCH2C H2-;6H,(CH3)2N-),1.71-1.21(m,78H,-CH2CH2CH2-,-CH2CH3),0.89(t,15H,-CH2CH3). MS(ESI):m / z=1048.9([M+H] + ). Example 3: Preparation of cationic lipid E3-1 The preparation process is as follows: At room temperature, calcium trifluoromethanesulfonate (Ca(OTf)2, 0.17 g, 0.5 mmol) was added to an acetonitrile solution of S1-8 (1.02 g, 1.0 mmol) and 1,2-epoxydodecane (S3-1, 0.18 g, 1.0 mmol), and the mixture was stirred at room temperature for 24 h. After the reaction was completed, the reaction solution was concentrated, the residue was dissolved in purified water, extracted with dichloromethane, the organic phase was dried over anhydrous magnesium sulfate, filtered, concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E3-1 (1.11 g). 1 H NMR(400MHz, CDCl3)δ:4.93-4.82(m,2H,-C(=O)OCH<),4.42-4.13(m,1H,>NCH<),4.06(t,4H,-C(=O)OCH2C H2CH2-),3.51-3.42(m,1H,-CH(OH)-),2.63(dd,1H,-CH(OH)CH2N<),2.50-2.32(m,7H;2H,>CHCH2CH2-;2H, (CH3)2NCH2-;1H,-CH(OH)CH2N<;2H,(CH3)2NCH2CH2CH2-),2.29-2.27(m,4H,-CH2C(=O)OCH<),2.20-2.00 (m,8H;2H,>CHCH2CH2-;6H,(CH3)2N-),1.72-1.20(m,92H,-CH2CH2CH2-,-CH2CH3),0.85(t,15H,-CH2CH3). MS(ESI):m / z=1149.1([M+H] + ). Example 4: Preparation of cationic lipid E4-1 Step a: Under ice bath conditions, (9Z,12Z)-octadec-9,12-dienal (S4-1, 2.64 g, 10.0 mmol), DL-proline (0.35 g, 3.0 mmol), and N-chlorosuccinimide were added to acetonitrile (40 mL), and the mixture was stirred at 0 °C for 2 h. After the reaction was complete, the reaction solution was diluted with anhydrous ethanol (30 mL), and sodium borohydride (0.53 g, 14.0 mmol) was added. The mixture was then stirred at 0 °C for another 4 h. After the reaction was complete, water (20 mL) was added to quench the reaction, and the mixture was extracted with methyl tert-butyl ether. The organic phase was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated to obtain compound (9Z,12Z)-2-chloro-octadec-9,12-dien-1-ol (S4-2, 2.81 g), which was used directly in the next reaction without purification. Step b: At room temperature, S4-2 (2.41 g, 8.0 mmol) and NaOH aqueous solution (5 M, 32 mL) were added to 1,4-dioxane (30 mL), and the reaction mixture was stirred at 35 °C for 2 h. After the reaction was completed, the reaction mixture was separated by a separatory funnel, the organic phase was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, concentrated, and purified by column chromatography to obtain compound S4-3 (1.56 g). Step c: At room temperature, Ca(OTf)₂ (0.34 g, 1.0 mmol) was added to an acetonitrile solution of S1-8 (2.03 g, 2.0 mmol) and S4-3 (0.53 g, 2.0 mmol), and the mixture was stirred at room temperature for 24 h. After the reaction was completed, the reaction solution was concentrated, the residue was dissolved in purified water, extracted with dichloromethane, the organic phase was dried over anhydrous magnesium sulfate, filtered, concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E4-1 (2.37 g). 1 H NMR(400MHz, CDCl3)δ:5.40-5.31(m,4H,-CH=CHCH2CH=CH-),4.92-4.80(m,2H,-C(=O)OCH<),4.41-4.15(m,1H,>NCH<),4.07(t,4 H,-C(=O)OCH2CH2CH2-),3.51-3.41(m,1H,-CH(OH)-),2.77(t,2H,-CH=CHCH2CH=CH-),2.64(dd,1H,-CH(OH)CH2N<),2.50-2.33(m ,7H;2H,>CHCH2CH2-;2H,(CH3)2NCH2-;1H,-CH(OH)CH2N<;2H,(CH3)2NCH2CH2CH2-),2.30-2.27(m,4H,-CH2C(=O)OCH<),2.23-1.9 9(m,12H;2H,>CHCH2CH2-;6H,(CH3)2N-;4H,-CH=CHCH2CH2-),1.70-1.18(m,90H,-CH2CH2CH2-,-CH2CH3),0.91(t,15H,-CH2CH3). MS(ESI):m / z=1229.1([M+H] + ). Example 5: Preparation of cationic lipid E5-1 The preparation process is as follows: Step a: Under nitrogen protection, DCC (1.34 g, 6.5 mmol) was added to a round-bottom flask containing 7-octenic acid (S5-1, 0.71 g, 5.0 mmol), n-hexanol (S5-2, 0.61 g, 6.0 mmol), and DMAP (0.15 g, 1.3 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, the filtrate was concentrated, and the crude product was purified by column chromatography to obtain S5-3 (0.93 g). Step b: S5-3 (0.68 g, 3.0 mmol) was dissolved in 20 mL of dichloromethane. Under ice bath conditions, m-chloroperoxybenzoic acid (m-CPBA, 0.78 g, 4.5 mmol) was added, and the mixture was stirred for 15 min. The ice bath was then removed, and the reaction was allowed to proceed overnight. After the reaction was complete, excess saturated sodium bisulfite solution was added to quench the reaction. The mixture was extracted with ethyl acetate (20 mL). The organic phase was washed successively with saturated sodium bicarbonate solution (20 mL x 3) and saturated sodium chloride solution (20 mL). The organic phase was dried over anhydrous magnesium sulfate, filtered, concentrated, and purified by column chromatography to obtain compound S5-4 (0.54 g). Step c: At room temperature, Ca(OTf)₂ (0.17 g, 0.5 mmol) was added to an acetonitrile solution of S1-8 (1.02 g, 1.0 mmol) and S5-4 (0.24 g, 1.0 mmol), and the mixture was stirred at room temperature for 24 h. After the reaction was completed, the reaction solution was concentrated, the residue was dissolved in purified water, extracted with dichloromethane, the organic phase was dried over anhydrous magnesium sulfate, filtered, concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E5-1 (1.18 g). 1H NMR(400MHz, CDCl3)δ:4.88-4.80(m,2H,-C(=O)OCH<),4.41-4.15(m,1H,>NCH<),4.07(t,6H,-C(=O)OCH2CH2CH2-) ,3.51-3.41(m,1H,-CH(OH)-),2.63(dd,1H,-CH(OH)CH2N<),2.50-2.34(m,7H;2H,>CHCH2CH2-;2H,(CH3)2NCH2-;1 H,-CH(OH)CH2N<;2H,(CH3)2NCH2CH2CH2-),2.31-2.26(m,6H;4H,-CH2C(=O)OCH<;2H,-(CH2)4CH2C(=O)OCH2-),2. 19-1.97(m,8H;2H,>CHCH2CH2-;6H,(CH3)2N-),1.70-1.19(m,90H,-CH2CH2CH2-,-CH2CH3),0.86(t,15H,-CH2CH3). MS(ESI):m / z=1245.1([M+H] + ). Example 6: Preparation of cationic lipid E6-1 The preparation process is as follows: Step a: Under nitrogen protection, DCC (1.34 g, 6.5 mmol) was added to a round-bottom flask containing S5-1 (0.71 g, 5.0 mmol) dissolved in dichloromethane (50 mL), pentadecane-7-ol (S6-1, 1.37 g, 6.0 mmol), and DMAP (0.15 g, 1.3 mmol). The reaction was carried out at room temperature for 16 h. After the reaction was completed, the precipitate was removed by filtration, the filtrate was concentrated, and the crude product was purified by column chromatography to obtain S6-2 (1.47 g). Step b: S6-2 (1.06 g, 3.0 mmol) was dissolved in 20 mL of dichloromethane. m-CPBA (0.78 g, 4.5 mmol) was added under ice bath conditions. The mixture was stirred for 15 min, then the ice bath was removed, and the reaction was allowed to proceed overnight. After the reaction was complete, excess saturated sodium bisulfite solution was added to quench the reaction. The mixture was extracted with ethyl acetate (20 mL). The organic phase was washed successively with saturated sodium bicarbonate solution (20 mL x 3) and saturated sodium chloride solution (20 mL). The organic phase was dried over anhydrous magnesium sulfate, filtered, concentrated, and purified by column chromatography to obtain compound S6-3 (0.83 g). Step c: At room temperature, Ca(OTf)₂ (0.17 g, 0.5 mmol) was added to an acetonitrile solution of S1-8 (1.02 g, 1.0 mmol) and S6-3 (0.37 g, 1.0 mmol), and the mixture was stirred at room temperature for 24 h. After the reaction was completed, the reaction solution was concentrated, the residue was dissolved in purified water, extracted with dichloromethane, the organic phase was dried over anhydrous magnesium sulfate, filtered, concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E6-1 (1.30 g). 1 H NMR(400MHz, CDCl3)δ:4.89-4.800(m,3H,-C(=O)OCH<),4.42-4.14(m,1H,>NCH<),4.04(t,4H,-C(=O)OCH2C H2CH2-),3.51-3.41(m,1H,-CH(OH)-),2.63(dd,1H,-CH(OH)CH2N<),2.50-2.32(m,7H;2H,>CHCH2CH2-;2H, (CH3)2NCH2-;1H,-CH(OH)CH2N<;2H,(CH3)2NCH2CH2CH2-),2.32-2.25(m,6H,-CH2C(=O)OCH<),2.20-1.96( m,8H;2H,>CHCH2CH2-;6H,(CH3)2N-),1.70-1.20(m,106H,-CH2CH2CH2-,-CH2CH3),0.87(t,18H,-CH2CH3). MS(ESI):m / z=1333.2([M+H] + ). Example 7: Preparation of cationic lipid E7-1 The preparation process is as follows: At room temperature, Ca(OTf)₂ (0.17 g, 0.5 mmol) was added to an acetonitrile solution of S₂-5 (0.91 g, 1.0 mmol) and S₃-1 (0.18 g, 1.0 mmol), and the mixture was stirred at room temperature for 24 h. After the reaction was complete, the reaction solution was concentrated, the residue was dissolved in purified water, extracted with dichloromethane, the organic phase was dried over anhydrous magnesium sulfate, filtered, concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E7-1 (1.07 g). 1H NMR(400MHz, CDCl3)δ:4.43-4.11(m,1H,>NCH<),4.06(t,8H,-C(=O)OCH2CH2CH2-),3.50-3.41(m,1 H,-CH(OH)-),2.63(dd,1H,-CH(OH)CH2N<),2.50-2.35(m,7H;2H,>CHCH2CH2-;2H,(CH3)2NCH2-;1H, -CH(OH)CH2N<;2H,(CH3)2NCH2CH2CH2-),2.31-2.26(m,2H,-OC(=O)CH(CH2)2-),2.22-1.97(m,8H; 2H,>CHCH2CH2-; 6H,(CH3)2N-),1.73-1.22(m,84H,-CH2CH2CH2-,-CH2CH3),0.90(t,15H,-CH2CH3). MS(ESI):m / z=1093.0([M+H] + ). Example 8: Preparation of cationic lipid E8-1 The preparation process is as follows: At room temperature, Ca(OTf)₂ (0.17 g, 0.5 mmol) was added to an acetonitrile solution of S₂-5 (0.91 g, 1.0 mmol) and S₄-3 (0.26 g, 1.0 mmol), and the mixture was stirred at room temperature for 24 h. After the reaction was complete, the reaction solution was concentrated, the residue was dissolved in purified water, extracted with dichloromethane, the organic phase was dried over anhydrous magnesium sulfate, filtered, concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E8-1 (1.13 g). 1H NMR(400MHz, CDCl3)δ:5.42-5.31(m,4H,-CH=CHCH2CH=CH-), 4.43-4.12(m,1H,>NCH<), 4.04(t,8H,-C(=O)OCH2CH2CH2-), 3.51-3.41(m,1H,-CH(OH)-),2.77(t,2H,-CH=CHCH2CH=CH-),2.63(dd,1H,-CH(OH)CH2N<),2.49-2.32(m,7H;2H,>CHCH2CH 2-;2H,(CH3)2NCH2-;1H,-CH(OH)CH2N<2H,(CH3)2NCH2CH2CH2-),2.30-2.25(m,2H,-OC(=O)CH(CH2)2-),2.21-2.00(m,12 H;2H,>CHCH2CH2-;6H,(CH3)2N-;4H,-CH=CHCH2CH2-),1.73-1.19(m,82H,-CH2CH2CH2-,-CH2CH3),0.89(t,15H,-CH2CH3). MS(ESI):m / z=1173.0([M+H] + ). Example 9: Preparation of cationic lipid E9-1 The preparation process is as follows: At room temperature, Ca(OTf)₂ (0.17 g, 0.5 mmol) was added to an acetonitrile solution of S₂-5 (0.91 g, 1.0 mmol) and S₅-4 (0.24 g, 1.0 mmol), and the mixture was stirred at room temperature for 24 h. After the reaction was completed, the reaction solution was concentrated, the residue was dissolved in purified water, extracted with dichloromethane, the organic phase was dried over anhydrous magnesium sulfate, filtered, concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E9-1 (1.11 g). 1H NMR(400MHz, CDCl3)δ:4.42-4.16(m,1H,>NCH<),4.03(t,10H,-C(=O)OCH2CH2CH2-),3.51-3.41(m,1H,-CH( OH)-),2.64(dd,1H,-CH(OH)CH2N<),2.50-2.32(m,7H;2H,>CHCH2CH2-;2H,(CH3)2NCH2-;1H,-CH(OH)CH2N<; 2H,(CH3)2NCH2CH2CH2-),2.32-2.28(m,4H; 2H,-OC(=O)CH(CH2)2-; 2H,-(CH2)4CH2C(=O)OCH2-),2.20-1.9 6(m,8H;2H,>CHCH2CH2-;6H,(CH3)2N-),1.73-1.22(m,82H,-CH2CH2CH2-,-CH2CH3),0.89(t,15H,-CH2CH3). MS(ESI):m / z=1151.0([M+H] + ). Example 10: Preparation of cationic lipid E10-1 The preparation process is as follows: At room temperature, Ca(OTf)₂ (0.17 g, 0.5 mmol) was added to an acetonitrile solution of S₂-5 (0.91 g, 1.0 mmol) and S₆-3 (0.37 g, 1.0 mmol), and the mixture was stirred at room temperature for 24 h. After the reaction was completed, the reaction solution was concentrated, the residue was dissolved in purified water, extracted with dichloromethane, the organic phase was dried over anhydrous magnesium sulfate, filtered, concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E10-1 (1.23 g). 1H NMR(400MHz, CDCl3)δ:4.91-4.80(m,1H,-C(=O)OCH<),4.39-4.12(m,1H,>NCH<),4.07(t,8H,-C(=O)OCH2CH2CH2- ),3.51-3.41(m,1H,-CH(OH)-),2.63(dd,1H,-CH(OH)CH2N<),2.50-2.32(m,7H;2H,>CHCH2CH2-;2H,(CH3)2NCH2- ;1H,-CH(OH)CH2N<;2H,(CH3)2NCH2CH2CH2-),2.32-2.25(m,4H; 2H,-OC(=O)CH(CH2)2-;2H,-CH2C(=O)OCH<),2.2 3-1.99(m,8H;2H,>CHCH2CH2-;6H,(CH3)2N-),1.74-1.19(m,98H,-CH2CH2CH2-,-CH2CH3),0.91(t,18H,-CH2CH3). MS(ESI):m / z=1277.1([M+H] + ). Example 11: Preparation of cationic lipid E11-1 The preparation process is as follows: Step a: Under nitrogen protection, DCC (3.22 g, 15.6 mmol) was added to a round-bottom flask containing S11-1 (2.94 g, 12.0 mmol), S1-3 (3.69 g, 14.4 mmol), and DMAP (0.37 g, 3.0 mmol) dissolved in dichloromethane (150 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 reaction solution was concentrated to obtain the crude product. The crude product was then dissolved in dichloromethane, TFA was added to a final concentration of 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 organic phase was dried over anhydrous magnesium sulfate, filtered, concentrated, and purified by column chromatography to obtain S11-2 (3.52 g). Step b: Dissolve S1-5 (1.24 g, 5.0 mmol) in 150 mL of anhydrous dichloromethane, add NHS (1.73 g, 15.0 mmol), and then add DCC (3.09 g, 15.0 mmol). Add DMAP (0.24 g, 2.0 mmol) to 50 mL of dichloromethane solution containing S11-2 (4.80 g, 12.5 mmol). Mix the two solutions and stir at room temperature for 24 h. After the reaction is complete, add saturated NaHCO3 (10 mL) to quench the reaction, remove the precipitate by filtration, extract three times with dichloromethane (50 mL * 3), combine the organic phases, dry with anhydrous magnesium sulfate, filter, concentrate, and obtain the crude product. The crude product was dissolved in dichloromethane, TFA was added to 0.1M, the reaction was carried out for 4 hours, the pH was adjusted to neutral, the reaction solution was concentrated, purified water was added, and the mixture was extracted with dichloromethane. The organic phase was dried with anhydrous magnesium sulfate, filtered, concentrated, and purified by column chromatography to obtain S11-3 (3.03 g). Step c: Under nitrogen protection, compound S11-3 (1.32 g, 1.5 mmol) was dissolved in acetonitrile (20 mL). S1-7 (0.37 g, 2.3 mmol) and DIPEA (0.39 g, 3.0 mmol) were added sequentially with slow stirring. The reaction mixture was stirred at room temperature for approximately 20 h. After the reaction was complete, the reaction solution was concentrated and dissolved in dichloromethane. The solution was then washed sequentially with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution. The organic phase was dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. Compound S11-4 (1.32 g) was purified by column chromatography. Step d: At room temperature, S11-4 (0.96 g, 1.0 mmol), triethylamine (0.51 g, 5.0 mmol), and DMAP (0.21 g, 1.7 mmol) were dissolved sequentially in toluene (20 mL). Then, a toluene solution of S1-9 (0.23 g, 1.3 mmol) was slowly added dropwise. After the addition was complete, the reaction mixture was stirred overnight at room temperature. After the reaction was complete, methanol (20 mL) was added to the reaction mixture to remove excess acyl chloride. The reaction mixture was concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E11-1 (0.87 g). 1H NMR(400MHz, CDCl3)δ:4.91-4.83(m,2H,-C(=O)OCH<),4.73-4.69(m,1H,>NCH<),3.28(dd,4H, -C(=O)NHCH2-),3.20-3.10(m,2H,(CH3)2NCH2CH2CH2-),2.82-2.35(m,4H;2H,>CHCH2CH2-;2H, (CH3)2NCH2-),2.33-2.27(m,6H;4H,-CH2C(=O)OCH<;2H,>NC(=O)CH2-),2.22-2.01(m,8H;2H,> CHCH2CH2-;6H,(CH3)2N-),1.72-1.19(m,86H,-CH2CH2CH2-,-CH2CH3),0.90(t,15H,-CH2CH3). MS(ESI):m / z=1103.0([M+H] + ). Example 12: Preparation of cationic lipid E12-1 The preparation process is as follows: At room temperature, Ca(OTf)₂ (0.17 g, 0.5 mmol) was added to an acetonitrile solution of S₁₁₄ (0.96 g, 1.0 mmol) and S₃₁ (0.18 g, 1.0 mmol), and the mixture was stirred at room temperature for 24 h. After the reaction was completed, the reaction solution was concentrated, the residue was dissolved in purified water, extracted with dichloromethane, the organic phase was dried over anhydrous magnesium sulfate, filtered, concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E₁₂₁ (1.21 g). 1H NMR(400MHz, CDCl3)δ:4.92-4.83(m,2H,-C(=O)OCH<),4.73-4.69(m,1H,>NCH<),3.50-3.41(m,1H,-CH (OH)-),3.29(dd,4H,-C(=O)NHCH2-),2.82-2.35(m,8H;2H,>CHCH2CH2-;1H,-CH(OH)CH2N<;2H,(CH3)2 NCH2-;1H,-CH(OH)CH2N<;2H,(CH3)2NCH2CH2CH2-),2.31-2.27(m,4H,-CH2C(=O)OCH<),2.20-1.97(m, 8H; 2H, > CHCH2CH2-; 6H, (CH3)2N-), 1.75-1.20 (m, 92H, -CH2CH2CH2-, -CH2CH3), 0.87 (t, 15H, -CH2CH3). MS(ESI):m / z=1147.1([M+H] + ). Example 13: Preparation of cationic lipid E13-1 The preparation process is as follows: At room temperature, Ca(OTf)₂ (0.17 g, 0.5 mmol) was added to an acetonitrile solution of S₁₁₄ (0.96 g, 1.0 mmol) and S₅₄ (0.24 g, 1.0 mmol), and the mixture was stirred at room temperature for 24 h. After the reaction was complete, the reaction solution was concentrated, the residue was dissolved in purified water, extracted with dichloromethane, the organic phase was dried over anhydrous magnesium sulfate, filtered, concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E13-1 (1.18 g). 1H NMR(400MHz, CDCl3)δ:4.90-4.81(m,2H,-C(=O)OCH<),4.73-4.69(m,1H,>NCH<),4.06(t,2H,-C(=O)OCH2CH2CH2-),3.51- 3.40(m,1H,-CH(OH)-),3.28(dd,4H,-C(=O)NHCH2-),2.63(dd,),2.82-2.36(m,8H;2H,>CHCH2CH2-;1H,-CH(OH)CH2N<;2H, (CH3)2NCH2-;1H,-CH(OH)CH2N<2H,(CH3)2NCH2CH2CH2-),2.32-2.27(m,6H;4H,-CH2C(=O)OCH<2H,-(CH2)4CH2C(=O)OCH 2-),2.20-2.00(m,8H;2H,>CHCH2CH2-;6H,(CH3)2N-),1.69-1.21(m,90H,-CH2CH2CH2-,-CH2CH3),0.86(t,15H,-CH2CH3). MS(ESI):m / z=1205.1([M+H] + ). Example 14: Preparation of cationic lipid E14-1 The preparation process is as follows: Step a: Under nitrogen protection, glycerol (S14-1, 3.71 g, 18.0 mmol) containing a TBS-protected hydroxyl group, potassium carbonate (K2CO3, 7.45 g, 54.0 mmol), and bromohexane (S14-2, 3.27 g, 19.8 mmol) were successively dissolved in 150 mL of DMF, and the reaction solution was stirred at 110 °C for 16 h. After the reaction was completed, the reaction solution was poured into water (100 mL) to precipitate, and then filtered. The obtained solid was dissolved in tetrahydrofuran (30 mL), and then 30 mL of TBAF tetrahydrofuran solution (1 M) was added. The reaction was allowed to proceed overnight to remove the TBS protection. After the reaction was completed, the solution was concentrated and extracted. The organic phase was dried over anhydrous magnesium sulfate, filtered, concentrated, and the crude product was purified by column chromatography to obtain compound S14-3 (4.06 g). Step b: Under nitrogen protection, DCC (3.22 g, 15.6 mmol) was added to a round-bottom flask containing S14-3 (3.74 g, 14.4 mmol), S1-2 (3.12 g, 12.0 mmol), and DMAP (0.37 g, 3.0 mmol) dissolved in dichloromethane (100 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 (30 mL), and then 30 mL of TBAF tetrahydrofuran solution (1 M) was added. The reaction was carried out overnight to remove TBS protection. After the reaction was completed, the mixture was concentrated and extracted. The organic phase was dried over anhydrous magnesium sulfate, filtered, concentrated, and the crude product was purified by column chromatography to obtain compound S14-4 (3.56 g). Step c: Under nitrogen protection, DCC (1.36 g, 6.6 mmol) was added to a round-bottom flask containing S1-5 (0.74 g, 3.0 mmol), S14-4 (2.92 g, 7.5 mmol), and DMAP (0.15 g, 1.2 mmol) dissolved in dichloromethane (50 mL). The reaction was carried out at room temperature for 16 h. After the reaction was completed, the precipitate was removed by filtration, and the reaction solution was concentrated to obtain the crude product. The crude product was then dissolved in dichloromethane, TFA was added to a final concentration of 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 organic phase was dried over anhydrous magnesium sulfate, filtered, concentrated, and purified by column chromatography to obtain S14-5 (2.18 g). Step d: Under nitrogen protection, compound S14-5 (1.43 g, 1.5 mmol) was dissolved in acetonitrile (20 mL). S1-7 (0.37 g, 2.3 mmol) and DIPEA (0.39 g, 3.0 mmol) were added sequentially with slow stirring. The reaction mixture was stirred at room temperature for approximately 20 h. After the reaction was complete, the reaction solution was concentrated and dissolved in dichloromethane. The solution was then washed sequentially with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution. The organic phase was dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. Compound S14-6 (1.32 g) was purified by column chromatography. Step e: At room temperature, S14-6 (0.97 g, 1.0 mmol), triethylamine (0.51 g, 5.0 mmol), and DMAP (0.21 g, 1.7 mmol) were dissolved sequentially in toluene (20 mL). Then, a toluene solution of S1-9 (0.23 g, 1.3 mmol) was slowly added dropwise. After the addition was complete, the reaction mixture was stirred overnight at room temperature. After the reaction was complete, methanol (20 mL) was added to the reaction mixture to remove excess acyl chloride. The reaction mixture was concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E14-1 (0.88 g). 1H NMR(400MHz, CDCl3)δ:5.16-5.02(m,2H,>CH(CH2OCH2)2-),4.38-4.14(m,1H,>NCH<),4.04(t,4H,-C(=O)OCH2CH2CH 2-),3.58-3.52(m,8H,>CH(CH2OCH2)2-),3.48-3.41(m,8H,>CH(CH2OCH2)2-),3.20-3.10(m,2H,(CH3)2NCH2CH2CH2 -),2.50-2.32(m,4H;2H,>CHCH2CH2-;2H,(CH3)2NCH2-),2.31-2.26(m,6H;4H,-CH2C(=O)OCH<;2H,>NC(=O)CH2-),2 .23-1.97(m,8H;2H,>CHCH2CH2-;6H,(CH3)2N-),1.74-1.22(m,62H,-CH2CH2CH2-,-CH2CH3),0.88(t,15H,-CH2CH3). MS(ESI):m / z=1112.9([M+H] + ). Example 15: Preparation of cationic lipid E15-1 The preparation process is as follows: At room temperature, Ca(OTf)₂ (0.17 g, 0.5 mmol) was added to an acetonitrile solution of S14-6 (0.97 g, 1.0 mmol) and S3-1 (0.18 g, 1.0 mmol), and the mixture was stirred at room temperature for 24 h. After the reaction was completed, the reaction solution was concentrated, the residue was dissolved in purified water, extracted with dichloromethane, the organic phase was dried over anhydrous magnesium sulfate, filtered, concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E15-1 (1.16 g). 1H NMR(400MHz, CDCl3)δ:5.16-5.02(m,2H,>CH(CH2OCH2)2-),4.41-4.14(m,1H,>NCH<),4.03(t,4H,-C(=O)OCH2CH2CH2-),3. 58-3.53(m,8H,>CH(CH2OCH2)2-),3.51-3.41(m,9H;1H,-CH(OH)-;8H,>CH(CH2OCH2)2-),2.63(dd,1H,-CH(OH)CH2N<),2.52 -2.34(m,7H;2H,>CHCH2CH2-;2H,(CH3)2NCH2-;1H,-CH(OH)CH2N<;2H,(CH3)2NCH2CH2CH2-),2.30-2.25(m,4H,-CH2C(=O)O CH<),2.18-1.96(m,8H;2H,>CHCH2CH2-;6H,(CH3)2N-),1.70-1.18(m,68H,-CH2CH2CH2-,-CH2CH3),0.86(t,15H,-CH2CH3). MS(ESI):m / z=1157.0([M+H] + ). Example 16: Preparation of cationic lipid E16-1 The preparation process is as follows: At room temperature, Ca(OTf)₂ (0.17 g, 0.5 mmol) was added to an acetonitrile solution of S14-6 (0.97 g, 1.0 mmol) and S5-4 (0.24 g, 1.0 mmol), and the mixture was stirred at room temperature for 24 h. After the reaction was completed, the reaction solution was concentrated, the residue was dissolved in purified water, extracted with dichloromethane, the organic phase was dried over anhydrous magnesium sulfate, filtered, concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E16-1 (1.19 g). 1H NMR(400MHz, CDCl3)δ:5.16-5.02(m,2H,>CH(CH2OCH2)2-),4.43-4.12(m,1H,>NCH<),4.06(t,6H,-C(=O)OCH2CH2CH2-),3.58-3.52 (m,8H,>CH(CH2OCH2)2-),3.51-3.41(m,9H;1H,-CH(OH)-;8H,>CH(CH2OCH2)2-),2.63(dd,1H,-CH(OH)CH2N<),2.51-2.32(m,7H;2H ,>CHCH2CH2-;2H,(CH3)2NCH2-;1H,-CH(OH)CH2N<;2H,(CH3)2NCH2CH2CH2-),2.30-2.25(m,6H;4H,-CH2C(=O)OCH<;2H,-(CH2)4CH2 C(=O)OCH2-),2.19-1.99(m,8H;2H,>CHCH2CH2-;6H,(CH3)2N-),1.70-1.19(m,66H,-CH2CH2CH2-,-CH2CH3),0.85(t,15H,-CH2CH3). MS(ESI):m / z=1215.0([M+H] + ). Example 17: Preparation of cationic lipid E17-1 The preparation process is as follows: Step a: At room temperature, S1-2 (2.60 g, 10.0 mmol), di-n-octylamine (S17-1, 5.30 g, 22.0 mmol), DIPEA (7.74 g, 60.0 mmol), and N,N,N',N'-tetramethylurea hexafluorophosphate (HATU, 9.88 g, 26.0 mmol) were successively dissolved in 250 mL of dichloromethane, and the reaction mixture was stirred overnight at room temperature. After the reaction was completed, saturated NaHCO3 (30 mL) was added to quench the reaction, and the mixture was extracted three times with ethyl acetate (100 mL * 3). The combined organic phases were dried over anhydrous magnesium sulfate, filtered, concentrated, and the crude product was dissolved in tetrahydrofuran (30 mL). Then, 30 mL of TBAF tetrahydrofuran solution (1 M) was added, and the reaction was allowed to proceed overnight to remove TBS protection. After the reaction was completed, the product was concentrated and extracted. The organic phase was dried with anhydrous magnesium sulfate, filtered, concentrated, and the crude product was purified by column chromatography to obtain compound S17-2 (3.00 g). Step b: Under nitrogen protection, DCC (1.36 g, 6.6 mmol) was added to a round-bottom flask containing S1-5 (0.74 g, 3.0 mmol), S17-2 (2.78 g, 7.5 mmol), and DMAP (0.15 g, 1.2 mmol) dissolved in dichloromethane (50 mL). The reaction was carried out at room temperature for 16 h. After the reaction was completed, the precipitate was removed by filtration, and the reaction solution was concentrated to obtain the crude product. The crude product was then dissolved in dichloromethane, TFA was added to a final concentration of 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 organic phase was dried over anhydrous magnesium sulfate, filtered, concentrated, and purified by column chromatography to obtain S17-3 (1.98 g). Step c: Under nitrogen protection, compound S17-3 (1.30 g, 1.5 mmol) was dissolved in acetonitrile (20 mL). S1-7 (0.37 g, 2.3 mmol) and DIPEA (0.39 g, 3.0 mmol) were added sequentially with slow stirring. The reaction mixture was stirred at room temperature for approximately 20 h. After the reaction was complete, the reaction solution was concentrated and dissolved in dichloromethane. The solution was then washed sequentially with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution. The organic phase was dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. Compound S17-4 (1.29 g) was purified by column chromatography. Step d: At room temperature, S17-4 (0.95 g, 1.0 mmol), triethylamine (0.51 g, 5.0 mmol), and DMAP (0.21 g, 1.7 mmol) were dissolved sequentially in toluene (20 mL). Then, a toluene solution of S1-9 (0.23 g, 1.3 mmol) was slowly added dropwise. After the addition was complete, the reaction mixture was stirred overnight at room temperature. After the reaction was complete, methanol (20 mL) was added to the reaction mixture to remove excess acyl chloride. The reaction mixture was concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E17-1 (0.86 g). 1H NMR(400MHz, CDCl3)δ:4.43-4.17(m,1H,>NCH<),4.04(t,4H,-C(=O)OCH2CH2CH2-),3.28-3.10 (m,10H;8H,-N(CH2CH2)2-;2H,(CH3)2NCH2CH2CH2-),2.50-2.33(m,4H;2H,>CHCH2CH2-;2H,(CH 3)2NCH2-),2.30-2.26(m,2H,>NC(=O)CH2-),2.24(t,4H,-CH2C(=O)N<),2.18-1.97(m,8H;2H,> CHCH2CH2-;6H,(CH3)2N-),1.71-1.20(m,78H,-CH2CH2CH2-,-CH2CH3),0.88(t,15H,-CH2CH3). MS(ESI):m / z=1075.0([M+H] + ). Example 18: Preparation of cationic lipid E18-1 The preparation process is as follows: At room temperature, Ca(OTf)₂ (0.17 g, 0.5 mmol) was added to an acetonitrile solution of S17-4 (0.95 g, 1.0 mmol) and S3-1 (0.18 g, 1.0 mmol), and the mixture was stirred at room temperature for 24 h. After the reaction was completed, the reaction solution was concentrated, the residue was dissolved in purified water, extracted with dichloromethane, the organic phase was dried over anhydrous magnesium sulfate, filtered, concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E18-1 (1.06 g). 1H NMR(400MHz, CDCl3)δ:4.42-4.15(m,1H,>NCH<),4.06(t,4H,-C(=O)OCH2CH2CH2-),3.51-3.41(m,1H,-CH (OH)-),3.28-3.19(m,8H,-N(CH2CH2)2-),2.63(dd,1H,-CH(OH)CH2N<),2.50-2.33(m,7H;2H,>CHCH2CH2 -;2H,(CH3)2NCH2-;1H,-CH(OH)CH2N<2H,(CH3)2NCH2CH2CH2-),2.25(t,4H,-CH2C(=O)N<),2.21-1.97( m,8H;2H,>CHCH2CH2-;6H,(CH3)2N-),1.73-1.21(m,84H,-CH2CH2CH2-,-CH2CH3),0.89(t,15H,-CH2CH3). MS(ESI):m / z=1119.1([M+H] + ). Example 19: Preparation of cationic lipid E19-1 The preparation process is as follows: At room temperature, Ca(OTf)₂ (0.17 g, 0.5 mmol) was added to an acetonitrile solution of S17-4 (0.95 g, 1.0 mmol) and S4-3 (0.26 g, 1.0 mmol), and the mixture was stirred at room temperature for 24 h. After the reaction was completed, the reaction solution was concentrated, the residue was dissolved in purified water, extracted with dichloromethane, the organic phase was dried over anhydrous magnesium sulfate, filtered, concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E19-1 (1.14 g). 1H NMR(400MHz, CDCl3)δ:5.40-5.32(m,4H,-CH=CHCH2CH=CH-),4.42-4.13(m,1H,>NCH<),4.06(t,4H,-C(=O)OCH2CH2CH2-),3.51- 3.40(m,1H,-CH(OH)-),3.28-3.20(m,8H,-N(CH2CH2)2-),2.76(t,2H,-CH=CHCH2CH=CH-),2.63(dd,1H,-CH(OH)CH2N<),2.50-2. 32(m,7H;2H,>CHCH2CH2-;2H,(CH3)2NCH2-;1H,-CH(OH)CH2N<;2H,(CH3)2NCH2CH2CH2-),2.23(t,4H,-CH2C(=O)N<),2.20-1.97( m,12H;2H,>CHCH2CH2-;6H,(CH3)2N-;4H,-CH=CHCH2CH2-),1.712-1.23(m,82H,-CH2CH2CH2-,-CH2CH3),0.89(t,15H,-CH2CH3). MS(ESI):m / z=1199.1([M+H] + ). Example 20: Preparation of cationic lipid E20-1 The preparation process is as follows: At room temperature, Ca(OTf)₂ (0.17 g, 0.5 mmol) was added to an acetonitrile solution of S17-4 (0.95 g, 1.0 mmol) and S5-4 (0.24 g, 1.0 mmol), and the mixture was stirred at room temperature for 24 h. After the reaction was completed, the reaction solution was concentrated, the residue was dissolved in purified water, extracted with dichloromethane, the organic phase was dried over anhydrous magnesium sulfate, filtered, concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E20-1 (1.12 g). 1H NMR(400MHz, CDCl3)δ:4.39-4.12(m,1H,>NCH<),4.04(t,6H,-C(=O)OCH2CH2CH2-),3.51-3.41(m,1H,-CH(OH)-),3. 28-3.19(m,8H,-N(CH2CH2)2-),2.63(dd,1H,-CH(OH)CH2N<),2.50-2.33(m,7H;2H,>CHCH2CH2-;2H,(CH3)2NCH2-;1H ,-CH(OH)CH2N<;2H,(CH3)2NCH2CH2CH2-),2.30-2.27(m,2H,-(CH2)4CH2C(=O)OCH2-),2.25(t,4H,-CH2C(=O)N<),2 .22-1.96(m,8H;2H,>CHCH2CH2-;6H,(CH3)2N-),1.68-1.19(m,90H,-CH2CH2CH2-,-CH2CH3),0.87(t,15H,-CH2CH3). MS(ESI):m / z=1177.1([M+H] + ). Example 21: Preparation of cationic lipid E21-1 The preparation process is as follows: Step a: Under nitrogen protection, compound S1-6 (1.32 g, 1.5 mmol) was dissolved in acetonitrile (20 mL), and 1-(2-bromoethyl)-4-methylpiperazine (S21-1, 0.47 g, 2.3 mmol, S21-1 was obtained by adding N-methylpiperazine) sequentially with slow stirring. With 1,2-dibromoethane The reaction mixture (prepared by reaction) and DIPEA (0.39 g, 3.0 mmol) were stirred at room temperature for about 20 h. After the reaction was completed, the reaction solution was concentrated and dissolved in dichloromethane, then washed successively with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution. The organic phase was dried with anhydrous magnesium sulfate, filtered, and the filtrate was concentrated and purified by column chromatography to obtain compound S21-2 (1.37 g). Step b: At room temperature, S21-2 (1.01 g, 1.0 mmol), triethylamine (0.51 g, 5.0 mmol), and DMAP (0.21 g, 1.7 mmol) were dissolved sequentially in toluene (20 mL). Then, a toluene solution of S1-9 (0.23 g, 1.3 mmol) was slowly added dropwise. After the addition was complete, the reaction mixture was stirred overnight at room temperature. After the reaction was complete, methanol (20 mL) was added to the reaction mixture to remove excess acyl chloride. The reaction mixture was concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E21-1 (0.90 g). 1 H NMR(400MHz, CDCl3)δ:4.90-4.81(m,2H,-C(=O)OCH<),4.42-4.16(m,1H,>NCH<),4.06(t,4H,-C (=O)OCH2CH2CH2-),3.20-3.10(m,2H,pip-CH2CH2-),2.62-2.33(m,15H;8H,pip-H;2H,pip-CH2C H2-;3H,pip-CH3;2H,>CHCH2CH2-),2.30-2.24(m,6H;4H,-CH2C(=O)OCH<;2H,>NC(=O)CH2-),2.2 1-1.98(m,2H,>CHCH2CH2-), 1.68-1.19(m,84H,-CH2CH2CH2-,-CH2CH3), 0.88(t,15H,-CH2CH3). MS(ESI):m / z=1146.0([M+H] + ). Example 22: Preparation of cationic lipid E22-1 The preparation process is as follows: Step a: Under nitrogen protection, compound S2-4 (1.24 g, 1.5 mmol) was dissolved in acetonitrile (20 mL). S21-1 (0.47 g, 2.3 mmol) and DIPEA (0.39 g, 3.0 mmol) were added sequentially with slow stirring. The reaction mixture was stirred at room temperature for approximately 20 h. After the reaction was complete, the reaction solution was concentrated and dissolved in dichloromethane. The solution was then washed sequentially with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution. The organic phase was dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. Compound S22-1 (1.30 g) was purified by column chromatography. Step b: At room temperature, S22-1 (0.95 g, 1.0 mmol), triethylamine (0.51 g, 5.0 mmol), and DMAP (0.21 g, 1.7 mmol) were dissolved sequentially in toluene (20 mL). Then, a toluene solution of S1-9 (0.23 g, 1.3 mmol) was slowly added dropwise. After the addition was complete, the reaction mixture was stirred overnight at room temperature. After the reaction was complete, methanol (20 mL) was added to the reaction mixture to remove excess acyl chloride. The reaction mixture was concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E22-1 (0.85 g). 1 H NMR(400MHz, CDCl3)δ:4.42-4.17(m,1H,>NCH<),4.06(t,8H,-C(=O)OCH2CH2CH2-),3.20 -3.10(m,2H,pip-CH2CH2-),2.64-2.32(m,15H; 8H,pip-H; 2H,pip-CH2CH2-; 3H,pip-CH3 ;2H,>CHCH2CH2-),2.30-2.25(m,4H;2H,-CH2OC(=O)CH<;2H,>NC(=O)CH2-),2.18-1.97( m,2H,>CHCH2CH2-),1.72-1.20(m,76H,-CH2CH2CH2-,-CH2CH3),0.89(t,15H,-CH2CH3). MS(ESI):m / z=1090.0([M+H] + ). Example 23: Preparation of cationic lipid E23-1 The preparation process is as follows: At room temperature, Ca(OTf)₂ (0.17 g, 0.5 mmol) was added to an acetonitrile solution of S₂₂-1 (0.95 g, 1.0 mmol) and S₃₁ (0.18 g, 1.0 mmol), and the mixture was stirred at room temperature for 24 h. After the reaction was completed, the reaction solution was concentrated, the residue was dissolved in purified water, extracted with dichloromethane, the organic phase was dried over anhydrous magnesium sulfate, filtered, concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E₂₃-1 (1.12 g). 1H NMR(400MHz, CDCl3)δ:4.38-4.16(m,1H,>NCH<),4.06(t,8H,-C(=O)OCH2CH2CH2-),3.51-3.41 (m,1H,-CH(OH)-),2.64(dd,1H,-CH(OH)CH2N<),2.61-2.32(m,18H;8H,pip-H;4H,pip-CH2CH2- ;2H,>CHCH2CH2-;1H,-CH(OH)CH2N<;3H,pip-CH3),2.30-2.25(m,2H,-OC(=O)CH(CH2)2-),2.19 -1.98(m,2H,>CHCH2CH2-),1.70-1.22(m,82H,-CH2CH2CH2-,-CH2CH3),0.89(t,15H,-CH2CH3). MS(ESI):m / z=1134.0([M+H] + ). Example 24: Preparation of cationic lipid E24-1 The preparation process is as follows: At room temperature, Ca(OTf)₂ (0.17 g, 0.5 mmol) was added to an acetonitrile solution of S₂₂-1 (0.95 g, 1.0 mmol) and S₄₃ (0.26 g, 1.0 mmol), and the mixture was stirred at room temperature for 24 h. After the reaction was completed, the reaction solution was concentrated, the residue was dissolved in purified water, extracted with dichloromethane, the organic phase was dried over anhydrous magnesium sulfate, filtered, concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E₂₄-1 (1.18 g). 1H NMR(400MHz, CDCl3)δ:5.40-5.31(m,4H,-CH=CHCH2CH=CH-),4.37-4.16(m,1H,>NCH<),4.05(t,8H,-C(=O)OCH2CH2CH2 -),3.51-3.41(m,1H,-CH(OH)-),2.76(t,2H,-CH=CHCH2CH=CH-),2.63(dd,1H,-CH(OH)CH2N<),2.61-2.33(m,18H;8H,p ip-H;4H,pip-CH2CH2-;2H,>CHCH2CH2-;1H,-CH(OH)CH2N<;3H,pip-CH3),2.31-2.27(m,2H,-OC(=O)CH(CH2)2-),2.17 -1.98(m,6H;2H,>CHCH2CH2-;4H,-CH=CHCH2CH2-),1.73-1.19(m,80H,-CH2CH2CH2-,-CH2CH3),0.89(t,15H,-CH2CH3). MS(ESI):m / z=1214.1([M+H] + ). Example 25: Preparation of cationic lipid E25-1 The preparation process is as follows: At room temperature, Ca(OTf)₂ (0.17 g, 0.5 mmol) was added to an acetonitrile solution of S22-1 (0.95 g, 1.0 mmol) and S5-4 (0.24 g, 1.0 mmol), and the mixture was stirred at room temperature for 24 h. After the reaction was complete, the reaction solution was concentrated, the residue was dissolved in purified water, extracted with dichloromethane, the organic phase was dried over anhydrous magnesium sulfate, filtered, concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E25-1 (1.13 g). 1H NMR(400MHz, CDCl3)δ:4.43-4.13(m,1H,>NCH<),4.07(t,10H,-C(=O)OCH2CH2CH2-),3.51-3.41(m,1H, -CH(OH)-),2.64(dd,1H,-CH(OH)CH2N<),2.62-2.34(m,18H;8H,pip-H;4H,pip-CH2CH2-;2H,>CHCH2CH2 -;1H,-CH(OH)CH2N<3H,pip-CH3),2.31-2.27(m,4H;2H,-OC(=O)CH(CH2)2-;2H,-(CH2)4CH2C(=O)OCH2 -),2.21-1.99(m,2H,>CHCH2CH2-),1.72-1.23(m,80H,-CH2CH2CH2-,-CH2CH3),0.87(t,15H,-CH2CH3). MS(ESI):m / z=1192.0([M+H] + ). Example 26: Preparation of cationic lipid E26-1 The preparation process is as follows: Step a: Under nitrogen protection, compound S14-5 (1.43 g, 1.5 mmol) was dissolved in acetonitrile (20 mL). S1-18 (0.47 g, 2.3 mmol) and DIPEA (0.39 g, 3.0 mmol) were added sequentially with slow stirring. The reaction mixture was stirred at room temperature for approximately 20 h. After the reaction was complete, the reaction solution was concentrated and dissolved in dichloromethane. The solution was then washed sequentially with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution. The organic phase was dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. Compound S26-1 (1.41 g) was purified by column chromatography. Step b: At room temperature, Ca(OTf)₂ (0.17 g, 0.5 mmol) was added to an acetonitrile solution of S26-1 (1.03 g, 1.0 mmol) and S3-1 (0.18 g, 1.0 mmol), and the mixture was stirred at room temperature for 24 h. After the reaction was completed, the reaction solution was concentrated, the residue was dissolved in purified water, extracted with dichloromethane, the organic phase was dried over anhydrous magnesium sulfate, filtered, concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E26-1 (1.23 g). 1H NMR(400MHz, CDCl3)δ:5.16-5.02(m,2H,>CH(CH2OCH2)2-),4.43-4.16(m,1H,>NCH<),4.06(t,4H,-C(=O)OCH2CH2CH 2-),3.58-3.52(m,8H,>CH(CH2OCH2)2-),3.51-3.41(m,9H;1H,-CH(OH)-;8H,>CH(CH2OCH2)2-),2.63(dd,1H,-CH(OH) )CH2N<),2.61-2.26(m,15H;2H,mep-CH2-;4H,mep-H;2H,>CHCH2CH2-;1H,-CH(OH)CH2N<;2H,mep-CH2CH2CH2-;4H,- CH2C(=O)OCH<),2.21-1.97(m,2H,>CHCH2CH2-),1.71-1.22(m,74H,-CH2CH2CH2-,-CH2CH3),0.86(t,15H,-CH2CH3). MS(ESI):m / z=1197.0([M+H] + ). Example 27: Preparation of cationic lipid E27-1 The preparation process is as follows: Step a: Under nitrogen protection, compound S17-3 (1.30 g, 1.5 mmol) was dissolved in acetonitrile (20 mL). S1-18 (0.47 g, 2.3 mmol) and DIPEA (0.39 g, 3.0 mmol) were added sequentially with slow stirring. The reaction mixture was stirred at room temperature for approximately 20 h. After the reaction was complete, the reaction solution was concentrated and dissolved in dichloromethane. The solution was then washed sequentially with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution. The organic phase was dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. Compound S27-1 (1.44 g) was purified by column chromatography. Step b: At room temperature, S27-1 (1.06 g, 1.0 mmol), triethylamine (0.51 g, 5.0 mmol), and DMAP (0.21 g, 1.7 mmol) were dissolved sequentially in toluene (20 mL). Then, a toluene solution of S1-9 (0.23 g, 1.3 mmol) was slowly added dropwise. After the addition was complete, the reaction mixture was stirred overnight at room temperature. After the reaction was complete, methanol (20 mL) was added to the reaction mixture to remove excess acyl chloride. The reaction mixture was concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E27-1 (0.88 g). 1H NMR(400MHz, CDCl3)δ:4.43-4.17(m,1H,>NCH<),4.05(t,4H,-C(=O)OCH2CH2CH2-),3.2 8-3.11(m,10H;8H,-N(CH2CH2)2-;2H,mep-CH2CH2CH2-),2.62-2.26(m,10H;2H,mep-CH2 -;4H,mep-H;2H,>CHCH2CH2-;2H,>NC(=O)CH2-),2.25(t,4H,-CH2C(=O)N<),2.22-1.99( m,2H,>CHCH2CH2-),1.71-1.21(m,84H,-CH2CH2CH2-,-CH2CH3),0.88(t,15H,-CH2CH3). MS(ESI):m / z=1115.0([M+H] + ). Example 28: Preparation of cationic lipid E28-1 The preparation process is as follows: At room temperature, Ca(OTf)₂ (0.17 g, 0.5 mmol) was added to an acetonitrile solution of S27-1 (1.06 g, 1.0 mmol) and S3-1 (0.18 g, 1.0 mmol), and the mixture was stirred at room temperature for 24 h. After the reaction was completed, the reaction solution was concentrated, the residue was dissolved in purified water, extracted with dichloromethane, the organic phase was dried over anhydrous magnesium sulfate, filtered, concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E28-1 (1.09 g). 1 H NMR(400MHz, CDCl3)δ:4.40-4.15(m,1H,>NCH<),4.05(t,4H,-C(=O)OCH2CH2CH2-),3.51-3.42(m,1H, -CH(OH)-),3.28-3.18(m,8H,-N(CH2CH2)2-),2.63(dd,1H,-CH(OH)CH2N<),2.62-2.31(m,11H;2H,mep -CH2-;4H,mep-H;2H,>CHCH2CH2-;1H,-CH(OH)CH2N<;2H,mep-CH2CH2CH2-),2.25(t,4H,-CH2C(=O)N< ),2.20-1.98(m,2H,>CHCH2CH2-),1.72-1.22(m,90H,-CH2CH2CH2-,-CH2CH3),0.90(t,15H,-CH2CH3). MS(ESI):m / z=1159.1([M+H] + ). Example 29: Preparation of cationic lipid E29-1 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 Boc-aspartic acid (S29-1, 0.70 g, 3.0 mmol), S1-4 (2.89 g, 7.5 mmol), and DMAP (0.15 g, 1.2 mmol) dissolved in dichloromethane (50 mL). The reaction was carried out at room temperature for 16 h. After the reaction was completed, the precipitate was removed by filtration, and the reaction solution was concentrated to obtain the crude product. The crude product was then dissolved in dichloromethane, TFA was added to a final concentration of 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 organic phase was dried over anhydrous magnesium sulfate, filtered, concentrated, and purified by column chromatography to obtain S29-2 (1.98 g). Step b: Under nitrogen protection, compound S29-2 (1.73 g, 2.0 mmol) was dissolved in acetonitrile (30 mL). S1-18 (0.62 g, 3.0 mmol) and DIPEA (0.52 g, 4.0 mmol) were added sequentially with slow stirring. The reaction mixture was stirred at room temperature for approximately 20 h. After the reaction was complete, the reaction solution was concentrated and dissolved in dichloromethane. The solution was then washed sequentially with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution. The organic phase was dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. Compound S29-3 (1.79 g) was purified by column chromatography. In step c, at room temperature, Ca(OTf)₂ (0.17 g, 0.5 mmol) was added to an acetonitrile solution of S29-3 (0.99 g, 1.0 mmol) and S3-1 (0.18 g, 1.0 mmol), and the mixture was stirred at room temperature for 24 h. After the reaction was complete, the reaction solution was concentrated, the residue was dissolved in purified water, extracted with dichloromethane, the organic phase was dried over anhydrous magnesium sulfate, filtered, concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E29-1 (1.10 g). 1H NMR(400MHz, CDCl3)δ:4.90-4.81(m,2H,-C(=O)OCH<),4.05(t,4H,-C(=O)OCH2CH2CH2-),3.9 0(t,1H,>NCH<),3.51-3.41(m,1H,-CH(OH)-),2.82-2.75(m,2H,>CHCH2-),2.63(dd,1H,-CH( OH)CH2N<),2.60-2.28(m,13H;2H,mep-CH2-;4H,mep-H;1H,-CH(OH)CH2N<;2H;mep-CH2CH2CH 2-;4H,-CH2C(=O)OCH<),1.73-1.23(m,98H,-CH2CH2CH2-,-CH2CH3),0.90(t,15H,-CH2CH3). MS(ESI):m / z=1175.1([M+H] + ). Example 30: Preparation of cationic lipid E30-1 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 S29-1 (0.70 g, 3.0 mmol), S2-3 (2.80 g, 7.5 mmol), and DMAP (0.15 g, 1.2 mmol) dissolved in dichloromethane (50 mL). The reaction was carried out at room temperature for 16 h. After the reaction was completed, the precipitate was removed by filtration, and the reaction solution was concentrated to obtain the crude product. The crude product was then dissolved in dichloromethane, TFA was added to a final concentration of 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 organic phase was dried over anhydrous magnesium sulfate, filtered, concentrated, and purified by column chromatography to obtain S30-1 (1.85 g). Step b: Under nitrogen protection, compound S30-1 (1.62 g, 2.0 mmol) was dissolved in acetonitrile (30 mL). S1-18 (0.62 g, 3.0 mmol) and DIPEA (0.52 g, 4.0 mmol) were added sequentially with slow stirring. The reaction mixture was stirred at room temperature for approximately 20 h. After the reaction was complete, the reaction solution was concentrated and dissolved in dichloromethane. The solution was then washed sequentially with 0.6 M hydrochloric acid / 10% sodium chloride solution and saturated sodium bicarbonate solution. The organic phase was dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. Compound S30-2 (1.69 g) was purified by column chromatography. Step c: At room temperature, S30-2 (0.94 g, 1.0 mmol), triethylamine (0.51 g, 5.0 mmol), and DMAP (0.21 g, 1.7 mmol) were dissolved sequentially in toluene (20 mL). Then, a toluene solution of S1-9 (0.23 g, 1.3 mmol) was slowly added dropwise. After the addition was complete, the reaction mixture was stirred overnight at room temperature. After the reaction was complete, methanol (20 mL) was added to the reaction mixture to remove excess acyl chloride. The reaction mixture was concentrated, and the crude product was purified by column chromatography to obtain cationic lipid E30-1 (0.85 g). 1 H NMR(400MHz, CDCl3)δ:4.53(t,1H,>NCH<),4.05(t,8H,-C(=O)OCH2CH2CH2-),3.30 (dd,1H,>CHCH2C(=O)O-),3.20-3.10(m,2H,mep-CH2CH2CH2-),2.72-2.65(m,1H,>C HCH2C(=O)O-),2.61-2.25(m,10H;2H,mep-CH2-;4H,mep-H;2H,-CH2OC(=O)CH<;2H, >NC(=O)CH2-),1.71-1.21(m,84H,-CH2CH2CH2-,-CH2CH3),0.88(t,15H,-CH2CH3). MS(ESI): m / z = 1074.9 ([M+H]) + ). Example 31: Preparation and Physicochemical Properties Testing of LNP-mRNA Drug Compositions Example 31.1: Preparation of LNP-mRNA Drug Composition In this embodiment, an LNP-mRNA pharmaceutical composition (LNP-mRNA) containing Fluc-mRNA was prepared. The phospholipids contained in the composition were all DSPC, the steroid lipids contained in the composition were all cholesterol, and the polyethylene glycol lipids contained in the composition were all PEG2k-DMG. The difference was that the composition was cationic lipid. The detailed formulations of each composition are summarized in Table 1. The method for preparing LNP-mRNA is as follows: Step a: Weigh a certain amount of cationic lipids, DSPC, cholesterol, and polyethylene glycol lipid stock solution. Dissolve the cationic lipids, DSPC, cholesterol, and polyethylene glycol lipids in ethanol at a molar ratio of 50:10:38:1.5 to obtain an ethanol phase solution. The cationic lipids used in the control groups LCT-1 and LCT-2 are C-1 and C-2, respectively. The cationic lipids used in the experimental groups L-1-1 to L-30 are all those with amino acid cores from Examples 1-30 of this application. C-1 is prepared according to the method disclosed in patent document WO2023240156A1, and C-2 is prepared according to the method disclosed in patent document WO2024022263A1. The structures of C-1 and C-2 are as follows: Step b: Add Fluc-mRNA to 10-50 mM citrate buffer (pH=4) to obtain an aqueous solution. Step c: Prepare LNP-mRNA by mixing the ethanol phase solution and the aqueous phase solution (1:3 v / v), and wash repeatedly with DPBS ultrafiltration to remove ethanol and free molecules. Finally, pass the solution through a 0.2 μm sterile filter for later use. Example 31.2: Physicochemical property testing of LNP-mRNA drug composition Encapsulation efficiency determination: The encapsulation efficiency of the LNP-mRNA composition prepared in Example 31.1 was determined using the Quant-it Ribogreen RNA quantification kit, and the results are summarized in Table 1. The results show that the lipid compositions (L-1-1 to L-30) of this application have high encapsulation efficiencies for nucleic acid drugs (mRNA), all within the range of 85%-96%, with most encapsulation efficiencies within the range of 90%-96%. The results indicate that the cationic lipids of the amino acid cores in each experimental group can effectively encapsulate mRNA, showing encapsulation efficiencies comparable to or better than C-1 or C-2. Differences also exist in the encapsulation efficiencies of the cationic lipids of different amino acid core structures. Particle size determination: In this embodiment, the particle size of LNP-mRNA was determined by dynamic light scattering (DLS). The measured LNP-mRNA showed high size uniformity, with a PDI of less than 0.3 for all samples. The LNP-mRNA prepared by the lipid composition of this application has a particle size in the range of 85-110 nm, which meets the requirements for particle size as a gene vector. Table 1: Summary of formulations of various lipid compositions and the particle size and encapsulation efficiency of the LNP-mRNA prepared from them. Example 32: Biological activity test of LNP-mRNA drug composition (1) Serum stability evaluation The LNP-mRNA drug composition prepared in Example 31.1 was added to a culture medium containing 10% fetal bovine serum (FBS) and stirred at 37°C. Samples were taken periodically to measure the particle size change of the LNP-mRNA, and the serum stability of the LNP-mRNA drug composition was analyzed by testing the particle size change. The experimental results showed that within 7 days, the particle size change in both the control and experimental groups was less than 10%, and the particle size change in all biological experimental groups was less than 5%, indicating that the LNP-mRNA drug composition prepared by cationic lipids in this application has excellent serum stability. (2) Cytotoxicity (biocompatibility) studies Prepare DMEM high-glucose complete medium containing 10% FBS. Prepare working solutions (0.1, 0.15, 0.2, 0.25, and 0.3 μg / 100 μL) for samples (L-1-1 to L-30, L-CT1, and L-CT2) using complete medium, respectively, and store for later use. Seed 293T cells in logarithmic growth phase at 7 × 10³ cells / well, 100 μL / well into 96-well plates. Both control and experimental groups have 6 replicates. After incubation for 24 h in a 5% CO2, 37°C incubator, retain the original medium. Add 100 μL / well of complete medium to the control group and 100 μL / well of working solution to the sample groups. Continue incubation for another 24 h, then add 100 μL / well of medium containing 10% CCK-8 and incubate for 2 h in a 5% CO2, 37°C incubator. Measure the absorbance at 450 nm using a microplate reader. Calculate the relative viability of cells using the following formula: Relative activity % = (sample absorbance value - background absorbance value) / (control group absorbance value - background absorbance value) × 100%; where the background absorbance value is the absorbance with only CCK-8 reagent and culture medium added. Experimental results showed that the LNP-mRNA drug composition prepared using the cationic lipids of this application did not produce significant cytotoxicity at any of the five concentration gradients, and the cell viability was greater than 95% in all cases. Figure 1 shows the cytotoxicity test results of L-9. (3) Evaluation of in vitro transfection effect To investigate the mRNA transfection rate at the cellular level of the LNP-mRNA drug compositions prepared in Example 31.1 of this application, Luciferase bioluminescence was used for testing. The LNP-mRNA drug compositions were dissolved in culture medium to prepare the required dosage. Using 293T cells as a cell model, 100 μL of cell suspension per well was seeded into 96-well plates with black edges and transparent bottoms at a seeding density of 6000 cells / well. After seeding, the cells were incubated in a cell culture incubator for 24 h. Then, 0.2 μg of mRNA was administered per well. The blank control group received 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 D-fluorescein sodium (1.5 mg / mL) substrate. After incubation for 5 minutes, bioluminescence was detected using a microplate reader. Stronger fluorescence indicated that more Fluc-mRNA was transported into the cytoplasm and translated into the corresponding fluorescent protein. The experimental results are shown in Table 2, where the relative fluorescence intensity is the ratio of the fluorescence intensity of each group to that of the blank control group. The results show that the LNP-mRNA drug compositions prepared in this application all exhibit excellent in vitro transfection effects, meaning that the LNPs in the experimental groups are all effective nucleic acid delivery carriers. The transfection efficiency of LNPs prepared by cationic lipids in this application is superior to that of L-CT1 and L-CT2 prepared by cationic lipids in the prior art. This may be because the cationic lipids with amino acid cores in this application contain more degradable linkers compared to C-1, avoiding endosome accumulation of lipids and promoting endosome escape of nucleic acids, thus showing better delivery effects. Compared to C-2, which contains two hydrocarbon tail chains, the cationic lipids in this application contain three hydrocarbon tail chains, and each of the three hydrocarbon tail chains is independently linear or branched, making it easier to form a cone-shaped structure, promoting lipid fusion with the endosome membrane, and thus promoting nucleic acid drug release. Some cationic lipids in this application have a hydroxyl group in one hydrocarbon tail chain, which enhances the hydrogen bond interaction between the lipid molecule and the phosphate backbone of the nucleic acid drug, helping to improve the stability of the LNP core after encapsulation, thereby improving the drug loading capacity of the LNP. As shown in Table 2 below, experimental groups L-1-2, L-1-3, L-1-4, L-3, L-4, L-5, L-10, L-6, L-7, L-8, L-9, L-10, L-17, L-18, L-19, and L-20 showed relatively high fluorescence values. At the same time, there were differences in fluorescence intensity among the experimental groups, which may be due to the following differences among the cationic lipids: the type and / or number of degradable linkers, and / or the type of hydrophobic hydrocarbon tail chain, and / or the saturation of the hydrophobic hydrocarbon tail chain, and / or the number of hydroxyl groups.Specifically, compared to E12-1 (L-12), E3-1, with its ester group as the linker between the hydrophobic hydrocarbon tail chain and the amino acid nucleus, showed a higher transfection rate than E12-1, which had an amide bond as the linker. This is likely because the degradable ester bond can prevent endosome accumulation of LNP-mRNA and promote endosome escape. Furthermore, E5-1, with its ester group in the hydrophobic hydrocarbon tail chain derived from the amino terminus of the amino acid nucleus, was superior to E3-1, further demonstrating that introducing an ester bond into the hydrophobic hydrocarbon tail chain results in better delivery. Comparing E1-1 (L-1-1), E1-2 (L-1-2), and E1-3 (L-1-3), the transfection rate was in the order E1-3 > E1-2 > E1-1. E1-3 contains two hydroxyl groups at its head, which can interact with phosphate groups on the nucleic acid through hydrogen bonding, thereby improving delivery efficiency. E3-1, which contains hydroxyl groups in its hydrophobic hydrocarbon tail chain, is superior to E1-1, further demonstrating that introducing hydroxyl groups into the hydrophobic hydrocarbon tail chain also improves the transfection rate. Table 2: Cell transfection test results (5) Evaluation of in vivo transfection effect Lipid nanoparticles L-9 were delivered to 6-8 week old female BALB / c mice via tail vein injection at a dose of 10 μg / mouse. In vivo fluorescence imaging was performed at 6, 12, and 24 hours after administration. After imaging at the last time point, the mice were euthanized, and imaging of the major organs (heart, liver, spleen, lung, and kidney) was performed (from left to right in the figure). 0.2 mL of D-fluorescein sodium (15 mg / mL) was injected intraperitoneally 10-15 min before imaging. The experimental results (Figure 2) show that the cationic lipid-based nucleic acid drug composition of this application can achieve efficient in vivo delivery of nucleic acid drugs, and the delivered LNP-mRNA drug composition is mainly distributed in the liver and spleen.

Claims

1. A cationic lipid having the structure shown in formula (1), Or its salts, tautomers, stereoisomers, deuterated derivatives or solvates; in, g is an integer from 1 to 6, f is 0 or 1, and n is 1 or 2; L e It is -CH(OH)- or -C(=O)-; N g The portion containing tertiary amines is selected from -NR. a R b Or -N r , where R a R b Each of the Cs can be substituted independently. 1-3 Alkyl groups, where Nr is a heterocyclic group containing a tertiary amine, are represented as... Nr contains at least one nitrogen atom as a cyclic atom, and optionally also contains one oxygen atom, one sulfur atom, or another nitrogen atom as a cyclic atom, with the remaining cyclic atoms being carbon atoms. R c These are groups drawn from the cyclic atom, selected from H, hydroxyl, and -(CH2). tg OH, C 1-6 Alkyl, C 1-6 Any of the alkoxy groups, tg is an integer from 1 to 6; p is R c The quantity, selected from integers from 1 to 6; L1 and L2 are each independently -C(=O)O- or -C(=O)NH-; the right ends of L1 and L2 are connected to B1 and B2 respectively; B1 and B2 are each independently optional substitutes for C. 1-8 Alkylene; L3 and L4 are each independently selected from -C(=O)-, -O-, and -O(CH2). s Any one of O-, -S-, -SS-, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -CH(OH)-, -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)O-, -OC(=S)O-, -NHC(=S)NH-, -NHC(=S)NH-, -OC(=S)NH- and -NHC(=S)O-, where s is 1, 2, 3 or 4; R1 and R2 are each independently C 1-30 Straight-chain hydrocarbon group, C 1-30 Branched hydrocarbon group, C 1-30 hydrocarbon derivative residues or Where t is an integer from 0 to 12, R e R f Each independently is C 1-15 Alkyl, C 2-15 alkenyl and C 2-15 Any of the alkynyl groups; R is C 1-30 Hydrocarbon group or C-aryl group interrupted by ester bond 1-30 hydrocarbon group; The term "optionally substituted" includes both "substituted" and "unsubstituted," and "substituted" means that at least one hydrogen atom is substituted by a substituent selected from -OH, -(CH2). g OH, -R d -C(=O)OR d -OC(=O)R d Any one of -X, where R d C 1-6 Alkyl group, where X is a halogen selected from -F, -Cl, -Br, and -I.

2. The cationic lipid according to claim 1, characterized in that, The N g Selected from Any one of them; preferably Any one of them; more preferably Any one of them.

3. The cationic lipid according to claim 1, characterized in that, R1 and R2 are each independently C 5-30 Straight-chain hydrocarbon group, C 5-30 Branched hydrocarbon group, C 5-30 hydrocarbon derivative residues or The C 5-30 The branched hydrocarbon group is C 5-30 Branched alkyl, C 5-30 Branched alkenyl or C 5-30 Branched alkynyl groups, each independently represented as The C 5-30 Hydrocarbon derivative residues are represented as Where t is an integer from 0 to 12, t1 and t2 are each independent integers from 0 to 5, t3 and t4 are each independent integers of 1, and each R e R f Independently for C 1-15 Alkyl, C 2-15 alkenyl or C 2-15 alkynyl group; the C 5-30 Straight-chain hydrocarbon group, C 5-30 Each branched hydrocarbon group is independently substituted or unsubstituted, and the substitution is preferably C. 1-6 Alkyl, halogen, or hydroxyl substitutions; The C 5-30 The straight-chain hydrocarbon group is C 5-30 straight-chain alkyl, C 5-30 Straight-chain alkenyl or C 5-30 Straight-chain alkynyl group; more preferably C 5-25 Straight-chain hydrocarbon group, more preferably C 5-17 Straight-chain hydrocarbon groups; More preferably, each of the aforementioned R e R f Independently for C 1-15 Alkyl, C 2-15 alkenyl or C 2-15 alkynyl group; R e R f More preferably, each is independently selected from any one of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, vinyl, propenyl, pentenyl, hexenyl, heptenyl, octenyl, nonenyl, decenyl, ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptenyl, octenyl, nonynyl, and decynyl; R e R f More preferably, each is independently selected from any one of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, and decyl.

4. The cationic lipid according to claim 3, characterized in that, R1 and R2 are any one of the following: Case (1): R1 and R2 are each independently C 5-30 Straight-chain hydrocarbon groups; Case (2): Either R1 or R2 is chosen as C. 5-30 The other is a straight-chain hydrocarbon group, and the other is C. 5-30 Branched hydrocarbon group Case (3): R1 and R2 are each independently C 5-30 Branched hydrocarbon group Case (4): R1 and R2 are each independent of each other. Case (5): Either R1 or R2 is chosen as C. 5-30 Straight-chain hydrocarbon group or C 5-30 Branched hydrocarbon group Another one is Case (6): Either R1 or R2 is chosen as The other is C 5-30 Straight-chain hydrocarbon group, C 5-30 Branched hydrocarbon group Case (7): R1 and R2 are each independent of each other. R1 and R2 that satisfy the above conditions are further preferably, wherein C 5-30 The straight-chain hydrocarbon group is selected from any of the following structures: Preferably, the C 5-30 The branched hydrocarbon group is selected from any of the following structures: Preferably, the Choose from any of the following structures: Preferably, the Choose from any of the following structures: Furthermore, it is preferable that t in R1 and R2 mentioned above is 0, 1 or 2.

5. The cationic lipid according to any one of claims 1-4, characterized in that, The R is C 5-30 Hydrocarbon group or C-aryl group interrupted by ester bond 5-30 hydrocarbon group, represented as Among them, B R It is any one of propylidene, butylidene, pentylidene, hexylidene, heptaylidene, and octylidene; L R For connecting key, -C(=O)O- or -OC(=O)-; R R For linear or branched C 5-18 hydrocarbon group; Furthermore, the aforementioned Preferably, any one of the following structures is selected:

6. The cationic lipid according to any one of claims 1-4, characterized in that, Each L3 and L4 is independently any one of -C(=O)-, -C(=O)O-, -OC(=O)-, -OC(=O)O-, -NHC(=O)O-, and -NHC(=O)-; each B1 and B2 is independently any one of butylene, pentylene, hexylene, heptylene, and octylene. Furthermore, each of the above is preferred. Independently, it can be any of the following structures:

7. The cationic lipid according to claim 1, characterized in that, When f is 0, L e When the carbon is -C (=O)-, the structural formula of the cationic lipid is (1-A); When f is 1, L e When the form is -CH(OH)-, the structure of the cationic lipid satisfies the corresponding formula (1-B); Preferably, B1 and B2 are each independently selected from butylene, pentylene, hexylene, heptylene, and octylene; R is C 5-30 Hydrocarbon group or C-aryl group interrupted by ester bond 5-30 hydrocarbon group, represented as Among them, B R It is any one of propylidene, butylidene, pentylidene, hexylidene, heptaylidene, and octylidene; L R For connecting key, -C(=O)O- or -OC(=O)-; R R For linear or branched C 5-18 Hydrocarbon group.

8. The cationic lipid according to claim 1, characterized in that, Its structure is selected from any of the following structures: Alternatively, the structure of the cationic lipid may be any of the following:

9. A lipid composition, characterized in that, The cationic lipid contained in any one of claims 1-8.

10. The lipid composition according to claim 9, characterized in that, The lipid composition further comprises one or more of phospholipids, steroid lipids, polyethylene glycol lipids, another cationic lipid, and anionic lipids; preferably, the lipid composition further comprises any one of phospholipids, steroid lipids, and polyethylene glycol lipids; more preferably, the lipid composition further comprises any two of phospholipids, steroid lipids, and polyethylene glycol lipids; even more preferably, the lipid composition further comprises phospholipids, steroid lipids, and polyethylene glycol lipids; most preferably, the lipid composition further comprises phospholipids, steroid lipids, polyethylene glycol lipids, and another cationic lipid; or the lipid composition further comprises phospholipids, steroid lipids, polyethylene glycol lipids, and anionic lipids; Preferably, the phospholipid is selected from 1,2-dilinoleoyl-sn-glycerol-3-phosphate choline, 1,2-dimyristoyl-sn-glycerol-3-phosphate choline, 1,2-dioleoyl-sn-glycerol-3-phosphate choline, 1,2-dipalmitoyl-sn-glycerol-3-phosphate choline, 1,2-distearateoyl-sn-glycerol-3-phosphate choline, 1,2-diundecanoyl-sn-glycerol-3-phosphate choline, and 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphate choline. Base, 1,2-di-O-octadecenyl-sn-glycerol-3-phosphate choline, 1-oleoyl-2-cholesterolylhemisuccinoyl-sn-glycerol-3-phosphate choline, 1-hexadecyl-sn-glycerol-3-phosphate choline, 1,2-dilinolenoyl-sn-glycerol-3-phosphate choline, 1,2-disarachidonicoyl-sn-glycerol-3-phosphate choline, 1,2-bis(docosahexaenoyl)-sn-glycerol-3-phosphate choline, 1,2-dioleoyl-sn-glycerol -3-phosphoethanolamine, 1,2-diphydanoyl-sn-glycerol-3-phosphoethanolamine, 1,2-distearatel-sn-glycerol-3-phosphoethanolamine, 1,2-dilinoleoyl-sn-glycerol-3-phosphoethanolamine, 1,2-dilinolenoyl-sn-glycerol-3-phosphoethanolamine, 1,2-diarachidonicoyl-sn-glycerol-3-phosphoethanolamine, 1,2-bis(docohexanoyl-sn-glycerol-3-phosphoethanolamine), 1,2-dioleoyl-s Sodium n-glycerol-3-phosphate-rac-(1-glycerol) salt, dioleoylphosphatidylserine, dipalmitoylphosphatidylglycerol, palmitoyloleoylphosphatidylethanolamine, distearate-phosphatidyl-ethanolamine, dipalmitoylphosphatidylethanolamine, dimyristoylphosphatidylethanolamine, 1-stearoyl-2-oleoylphosphatidylcholine, sphingomyelin, phosphatidylinositol, phosphatidic acid, palmitoyloleoylphosphatidylcholine, lysophosphatidylcholine and lysophosphatidylethanolamine, any one of the following and combinations thereof; Preferably, the steroid lipids are selected from any one of cholesterol, coccosterol, sitosterol, ergosterol, campesterol, stigmasterol, rapeseed sterol, tomatine, ursolic acid, α-tocopherol, and combinations thereof. Preferably, the polyethylene glycol lipid is selected from polyethylene glycol-1,2-dimyristoylglycerol, polyethylene glycol-distearylphosphatidylethanolamine, PEG-cholesterol, polyethylene glycol-diacylglycerol, polyethylene glycol-dialkoxypropyl, specifically including polyethylene glycol 500-dispalmitoylphosphatidylcholine, polyethylene glycol 2000-dispalmitoylphosphatidylcholine, polyethylene glycol 500-distearylphosphatidylethanolamine, polyethylene glycol 2000-distearylphosphatidylethanolamine, polyethylene glycol 500-1,2-dioleoylphosphatidylethanolamine, polyethylene glycol 2000-1,2-dioleoylphosphatidylethanolamine and polyethylene glycol 2000-2,3-dimyristoylglycerol and combinations thereof, or the polyethylene glycol lipid is selected from any one of the following structures and combinations thereof: Wherein, n1 is an integer between 25 and 300, and more preferably n1 is any one of 44, 45, 46, 47, and 48; Preferably, the other cationic lipid is selected from 1,2-dioleoyl-3-trimethylammonium-propane (methyl sulfate), 1,2-bisoctadecenoxy-3-methylammonium propane chloride, 1-[2-(oleoyloxy)ethyl]-2-oleo-3-(2-hydroxyethyl)imidazoline chloride, 1,2-dioleoyl-3-dimethylamino-propane, 2,3-bis(tetradecanoyloxy)propyltrimethylazone chloride, bisdecyldimethylammonium chloride, bisdecyldimethylammonium bromide, N,N-dioleo-N,N-dimethylammonium chloride, N-(4-carboxybenzyl)-N,N-dimethyl-2,3-bis(oleoyloxy)prop-1-ammonium, 3,6-bis{4-[bis(2-hydroxydodecyl)amino]butyl}piperazine-2,5-dione, 1,1'-( Any one of (2-(4-(2-((2-(bis(2-hydroxydodecyl)amino)ethyl)(2-hydroxydodecyl)amino)ethyl)piperazine-1-yl)ethyl)azadiyl)bis(dodecane-2-ol), methyl 4-(N,N-dimethylamino)butyrate (dilinoleyl) ester, 1,2-dimyristoyl-sn-glycerol-3-ethylphosphocholine, ((4-hydroxybutyl)azadiyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate), 8-[(2-hydroxyethyl)(6-oxo-6-(undecyloxy)hexyl)amino]octanoate (heptadecane-9-yl) ester and ((2-(2-hydroxyethoxy)ethyl)azadiyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate) and combinations thereof; Preferably, the anionic lipid is selected from any one of 1,2-dioleoyl-sn-glycerol-3-phosphate sodium salt, 1,2-dimyristoyl-sn-glycerol-3-phosphate sodium salt, bis(monooleoylglycerol) phosphate ammonium salt and cardiolipin, and combinations thereof.

11. The lipid composition according to claim 10, characterized in that, It contains 20-80% cationic lipids, 5-16% phospholipids, 25-55% steroid lipids and 0.5-10% polyethylene glycol lipids, where the percentages are the molar percentages of each lipid in the total lipids. Preferably, the cationic lipids account for 30-65% of the total lipids; more preferably, they are any one of 35%, 40%, 45%, 46%, 47%, 48%, 49%, 50%, and 55%. Preferably, the phospholipids account for 7.5-16% of the total lipids; more preferably, they are any one of 8%, 9%, 10%, 11%, 12%, and 16%. Preferably, the steroid lipids account for 35-50% of the total lipids in molar percentage, more preferably any one of 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, and 50%. Preferably, the polyethylene glycol lipid accounts for 0.5-5% of the total lipid molar percentage; more preferably 1-3%; and even more preferably any one of 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2.0%, and 2.5%.

12. A lipid pharmaceutical composition, characterized in that, The lipid composition and drug comprising any one of claims 9-11, wherein the drug is selected from any one of nucleic acid drugs, gene vaccines, antitumor drugs, small molecule drugs, peptide drugs or protein drugs; wherein the nucleic acid drug is selected from any one of RNA, DNA, antisense nucleic acid, plasmid, interfering nucleic acid, aptamer, antagomir and ribozyme; preferably the RNA is selected from any one of mRNA, saRNA, circRNA, miRNA and siRNA; more preferably the nucleic acid drug is any one of DNA, mRNA, miRNA and siRNA.

13. The lipid pharmaceutical composition according to claim 12, characterized in that, The lipid pharmaceutical composition is used to prepare a drug, which is selected from any one of antitumor agents, antiviral agents, antifungal agents, and vaccines.

14. A liposome or lipid nanoparticle, characterized in that, A lipid composition comprising any one of claims 9-11.

15. A lipid pharmaceutical composition formulation, characterized in that, The pharmaceutical composition, liposomes, or lipid nanoparticles contained in any one of claims 12-14 further contain a pharmaceutically acceptable diluent or excipient, wherein the diluent or excipient is preferably any one of deionized water, ultrapure water, phosphate buffer, and physiological saline, more preferably phosphate buffer or physiological saline, and most preferably physiological saline.

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