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.

Abstract: Disclosed are a multifunctionalized polyethylene glycol derivative and a preparation method therefor. The derivative has an H-shaped structure as represented by formula (1) and comprises one linear core LPEG and four PEG branch chains, where n1, n2, n3, and n4 respectively are the degrees of polymerization of the branch chains, U1 and U2 are trivalent branching groups connecting the core LPEG to two of the PEG branch chains, F1 and F2 contain a functional group or a protected form R01 thereof and may or may not contain a branched group G, correspondingly, the number of R01 is one or more, F1 and F2 are either identical or different, any one linking group in the molecule or any linking group formed with an adjacent heteroatom group can either remain stable or be degraded, and any one PEG segment in the molecule is discretely polydispersed or monodispersed.

Abstract: The monofunctional branched poly(ethylene glycol) (PEG) has a general formula shown in formula (1), and the bio-related substance modified by the monofunctional branched PEG has a general formula shown in formula (2), wherein X1 and X2 are each independently a hydrocarbon group having 1 to 20 carbon atoms, n1 and n2 are each independently an integer selected from 1 to 1000, n3 is an integer selected from 11 to 1000, L1, L2 are each independently a linking group, p is 0 or 1, q is 0 or 1, R1 is a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms, D is a bio-related substance, Z is a linking group, and Z can react with the bio-related substance to form a residue group L3. The PEG-modified bio-related substance maintains good biological activity, and has better solubility and a longer half-life in vivo.

Abstract: Disclosed are an 8-arm polyethylene glycol (PEG) derivative (formula 1), manufacturing method and modified bio-related substance thereby, wherein a tetravalent group U and four trivalent groups Ec form a highly symmetric octavalent central structure CORE0 together, Lc connects the octavalent center to eight PEG arms having polydiversity or monodiversity and having n1-n8 as the degrees of polymerization thereof. The terminal of one PEG chain is connected to at least one functional group F (k?1), and said PEG chain and F can be directly connected (g=0) or connected with a divalent linking group L0 connected with a terminal branched group G (g=1) therebetween. The latter provides more reacting sites to combine more pharmaceutical molecules, thereby increasing the drug loading capacity.

Abstract: Disclosed are an 8-arm polyethylene glycol (PEG) derivative (formula 1), manufacturing method and modified bio-related substance thereby, wherein a tetravalent group U and four trivalent groups Ec form a highly symmetric octavalent central structure CORE0 together, Lc connects the octavalent center to eight PEG arms having polydiversity or monodiversity and having n1-n8 as the degrees of polymerization thereof. The terminal of one PEG chain is connected to at least one functional group F (k?1), and said PEG chain and F can be directly connected (g=0) or connected with a divalent linking group L0 connected with a terminal branched group G (g=1) therebetween. The latter provides more reacting sites to combine more pharmaceutical molecules, thereby increasing the drug loading capacity.

Abstract: Disclosed are an eight-arm polyethylene glycol (PEG) derivative (formula I), production method therefor and modified bio-related substance thereby. Wherein, one tetravalent group U together with four trivalent groups Ec form a highly symmetrical octavalent group CORE0; Lc connects the octavalent group to eight PEG chains having polydispersity or monodispersity and having n1 to n8 as the degree of polymerization thereof; the terminal of one PEG chain is connected to at least one functional group F (k?1); said PEG chain and F therebetween can be directly connected (g=0) or be indirectly connected via a linking group L0 to a terminal end-branching group G (g=1); the latter provides more reactive sites for binding more drug molecules and increases the drug loading.

Abstract: Disclosed are an eight-arm polyethylene glycol (PEG) derivative (formula I), production method therefor and modified bio-related substance thereby. Wherein, one tetravalent group U together with four trivalent groups Ec form a highly symmetrical octavalent group CORE0; Lc connects the octavalent group to eight PEG chains having polydispersity or monodispersity and having n1 to n8 as the degree of polymerization thereof; the terminal of one PEG chain is connected to at least one functional group F (k?1); said PEG chain and F therebetween can be directly connected (g=0) or be indirectly connected via a linking group L0 to a terminal end-branching group G (g=1); the latter provides more reactive sites for binding more drug molecules and increases the drug loading.

Abstract: Disclosed are a multifunctionalized polyethylene glycol derivative and a preparation method therefor. The derivative has an H-shaped structure as represented by formula (1) and comprises one linear core LPEG and four PEG branch chains, where n1, n2, n3, and n4 respectively are the degrees of polymerization of the branch chains, U1 and U2 are trivalent branching groups connecting the core LPEG to two of the PEG branch chains, F1 and F2 contain a functional group or a protected form R01 thereof and may or may not contain a branched group G, correspondingly, the number of R01 is one or more, F1 and F2 are either identical or different, any one linking group in the molecule or any linking group formed with an adjacent heteroatom group can either remain stable or be degraded, and any one PEG segment in the molecule is discretely polydispersed or monodispersed.

Abstract: The monofunctional branched poly(ethylene glycol) (PEG) has a general formula shown in formula (1), and the bio-related substance modified by the monofunctional branched PEG has a general fomula shown in formula (2), wherein X1 and X2 are each independently a hydrocarbon group having 1 to 20 carbon atoms, n1 and n2 are each independently an integer selected from 1 to 1000, n3 is an integer selected from 11 to 1000, L1, L2 are each independently a linking group, p is 0 or 1, q is 0 or 1, R1 is a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms, D is a bio-related substance, Z is a linking group, and Z can react with the bio-related substance to form a residue group L3. The PEG-modified bio-related substance maintains good biological activity, and has better solubility and a longer half-life in vivo.