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 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.