Abstract: A novel cationic lipid has a structure as represented by general formula (1) and specifically relates to a nitrogen-branched cationic lipid, and a liposome containing the cationic lipid, and a nucleic-acid pharmaceutical composition containing the liposome, a preparation method and application thereof, wherein, the definition of each symbol in the formula (1) is as defined herein. The cationic liposome containing the cationic lipid as represented by formula (1) can improve the loading rate and transport efficiency of nucleic-acid drugs. The formulation of the cationic liposome nucleic-acid pharmaceutical composition has good cell compatibility and higher gene transfection capability, and can improve the treatment and/or prevention effects of nucleic-acid drugs.

Abstract: An improved method for preparing polyethylene glycol acetal and aldehyde derivative, and the polyethylene glycol acetal derivative is represented by formula (1) or formula (2) used to preparing a series of linear and nonlinear polyethylene glycolaldehyde derivatives with a single aldehyde group or multiple aldehyde groups, and with high yield, high purity and high terminal substitution, using a small-molecule cyclic acetal derivative and a polyethylene glycol derivative as raw materials in the presence of a base reagent derivative.

Abstract: A novel amino acid-based cationic lipid contains unsaturated bonds, represented by the general formula (1). The amino acids or derivatives used as starting materials in the preparation process are simple and easily obtainable, offering simplicity, safety, and cost-effectiveness. The amino acid-based cationic lipid of this invention features unsaturated hydrocarbon tails and a tertiary amine moiety derived from an amino acid residue. The lipid nanoparticles (LNPs) prepared from this lipid exhibit enhanced membrane fluidity, which improves membrane fusion and facilitates cellular uptake. As a result, the delivery efficiency of the amino acid-based cationic lipid containing unsaturated bonds as a delivery material is significantly improved.

Abstract: The present invention discloses a non-linear PEGylated lipid, including the structure represented by the Formula (1); wherein, B1 and B2 are linking bonds or alkylene groups; L1 and L2 are linking bonds or divalent linking groups; Lx, Y, and Ld are divalent linking groups; R1 and R2 are C4-50 hydrocarbon groups or C4-50 residues of hydrocarbon derivative containing 1-4 heteroatoms; X is —CH< or n1, n2, and n3 are integers in the range of 4-250; T is a terminal group. Compared with linear PEGylated lipids, the non-linear PEGylated lipid provided herein can realize better protective effects toward the modified LNPs. The lipid pharmaceutical composition of the present invention exhibits high efficiency of drug encapsulation, appropriate particle size, non-toxicity, and good stability in serum. The LNP-nucleic acid pharmaceutical composition of the present invention demonstrates an excellent ability to complex with nucleic acids and shows high transfection activity.

Abstract: A non-linear PEGylated lipid of the Formula (1) contains a tertiary amine; wherein, B1 and B2 are linking bonds or alkylene groups; L1, L2, Ld, and Lx are linking bonds or divalent linking groups; R1 and R2 are C1-50 aliphatic hydrocarbon groups or C1-50 residues of aliphatic hydrocarbon derivatives, each containing 0-10 heteroatoms; y is 2 or 3; X is C or CH; XPEG is a polyethylene glycol component. Compared with linear PEGylated lipids, the PEGylated lipid can realize better surface modification of LNP, better protective effects, extended systemic circulation of LNP, and significantly reduced biological toxicity of LNP. The LNP pharmaceutical composition shows excellent drug delivery capabilities. The lipid-nucleic acid pharmaceutical composition and its formulation exhibit higher pharmaceutical efficacy, especially the LNP-nucleic acid pharmaceutical composition.

Abstract: A nitrogen-branched non-linear PEGylated lipid containing a tertiary amine, which is represented by the Formula (1); wherein, B1 and B2 are linking bonds or alkylene groups; L1, L2, Ld and Lx are linking bonds or divalent linking groups L; R1 and R2 are C1-50 aliphatic hydrocarbon groups or C1-50 residues of aliphatic hydrocarbon derivative, each containing 0-10 heteroatoms; Ncore is a multivalent group of valence y+1 and contains a trivalent nitrogen-atom branching core connected to Ld; y is 2, 3, 4, 5, 6, 7, 8, 9, or ?10; XPEG are polyethylene glycol components. Compared with linear PEGylated lipids, the nitrogen-branched PEGylated lipid herein can realize better surface modification of LNP. The present invention also provides a lipid pharmaceutical composition and its formulation containing the PEGylated lipid, which can enhance the targeting ability of drugs and improve the transfection efficiency of nucleic acid drugs.

Abstract: A nitrogen-branched non-linear PEGylated lipid of Formula (1), wherein, X is —CRa< or (Ra is H or a C1-12 alkyl group); B1 and B2 are linking bonds or C1-20 alkylene groups; L1 and L2 are linking bonds or divalent linking groups; R1 and R2 are C1-50 aliphatic hydrocarbon groups or C1-50 residues of aliphatic hydrocarbon derivative, each containing 0-10 heteroatoms; Ld is a linking bond or a divalent linking group; Ncore is a multivalent group of valence y+1, and contains a trivalent nitrogen-atom branching core connected to Ld; y is 2, 3, 4, 5, 6, 7, 8, 9, or ?10; Lx is a linking bond or a divalent linking group; XPEG is a polyethylene glycol component. The non-linear PEGylated lipid herein can realize better surface modification of LNP. The lipid nanoparticle pharmaceutical composition and its formulation exhibit higher drug efficacy, especially for nucleic acid drugs.

Abstract: A novel type of cationic lipid and PEGylated derivative thereof, a cationic liposome and a cationic liposome-nucleic acid pharmaceutical composition containing the cationic lipid and formulation thereof include an ionizable lipid compound of the general formula (1). This compound is slightly ionized or neutral at physiological pH but undergoes greater ionization under acidic conditions, exhibiting lower toxicity in the systemic circulation and improved endosomal escape ability. The compound's polar head contains an ionizable tertiary amine group along with a side chain containing functional groups, while the tail chains may include linking groups that are easily degraded. Cationic liposomes containing the compound have a better ability to complex with nucleic acid drugs, higher stability in serum, no apparent cytotoxicity, and high transfection efficiency.

Abstract: A novel cationic lipid has a structure as represented by general formula (1) and specifically relates to a nitrogen-branched cationic lipid, and a liposome containing the cationic lipid, and a nucleic-acid pharmaceutical composition containing the liposome, a preparation method and application thereof, wherein, the definition of each symbol in the formula (1) is as defined herein. The cationic liposome containing the cationic lipid as represented by formula (1) can improve the loading rate and transport efficiency of nucleic-acid drugs. The formulation of the cationic liposome nucleic-acid pharmaceutical composition has good cell compatibility and higher gene transfection capability, and can improve the treatment and/or prevention effects of nucleic-acid drugs.

Abstract: A novel cationic lipid having a structure as represented by general formula (1), which specifically relates to a nitrogen-containing cationic lipid, and also relates to a liposome containing the cationic lipid, a liposome pharmaceutical composition containing said cationic lipid, preparation and application thereof. A cationic liposome containing the cationic lipid represented by formula (1), can improve the loading rate and transport rate of drugs, particularly nucleic acid drugs. The terminus of the novel cationic lipid can contain a fluorescent group or a targeting group, so that the cationic liposome pharmaceutical composition containing the cationic lipid can have fluorescent or targeting function.

Abstract: A novel PEGylated lipid and preparation methods thereof, a cationic liposome containing the PEGylated lipid, a pharmaceutical composition containing the liposome, a formulation and application thereof. The PEGylated lipid can be used for modifying a liposome, and it can be further modified and coupled with a targeting group, and then used for modifying a liposome to obtain a liposome with the targeting group. Due to the presence of a long-chain PEG and the targeting group on the lipid, the modified liposome can avoid being removed by the reticuloendothelial system in a human body and realize a targeting function. Therefore, when the modified liposome delivers an active drug to cells or a patient, especially when delivering a nucleic acid or anti-tumor drug, the liposome can realize long circulation in vivo and improve the transport efficiency of drug, and has a targeting unction so the therapeutic effect of a drug is improved.

Abstract: A novel PEGylated lipid and preparation methods thereof, a cationic liposome containing the lipid, a pharmaceutical composition containing the liposome, a formulation and application thereof. The PEGylated lipid can be used for modifying a liposome, and can be further modified and coupled with a targeting group and then used for modifying a liposome to obtain a liposome having the targeting group. Due to the presence of a long-chain PEG and the targeting group on the lipid, the modified liposome can avoid being removed by the reticuloendothelial system in a human body and realize a targeting function. Therefore, when the modified liposome delivers an active drug to cells or a patient, especially when delivering a nucleic acid or anti-tumor drug, the liposome can realize long circulation in vivo and improve the transport efficiency of drug, and has a targeting function, so the therapeutic effect of a drug is improved.