Cationic lipid, liposome containing cationic lipid, and nucleic-acid pharmaceutical composition containing liposome and formulation and application thereof

A cationic lipid, wherein, the structure is represented by the general formula (1):

• wherein N is the nitrogen-atom branching center;
• wherein one of L1 and L2 is —OC(═O)—, —C(═O)O—, or —OC(═O)O—, the other is —C(═O)O—, —OC(═O)O—, or —C(═O)—;
• wherein;
• L3 is selected from the group consisting of a linking bond, -L4-, —Z-L4-, -L4-Z—, —Z-L4-Z—, -L4-Z-L5-, —Z-L4-Z-L5-, and -L4-Z-L5-Z—;
• wherein, said L4 and L5 are carbon-chain linking groups, each independently represented by —(CRaRb)t—(CRaRb)o—(CRaRb)p—;
• wherein t, o, and p are each independently an integer from 0 to 12, not being 0 simultaneously;
• wherein Ra and Rb are, at each occurrence, independently a hydrogen atom or a C1-6 alkyl group;
• wherein said Z is, at each occurrence, independently selected from the group consisting of —C(═O)—, —OC(═O)—, —C(═O)O—, —OC(═O)O—, —O—, —S—, —C(═O)S—, —SC(═O)—, —NRcC(═O)—, —C(═O)NRc—, —NRcC(═O)NRc—, —OC(═O)NRc—, —NRcC(═O)O—, —SC(═O)NRc—, —NRcC(═O)S—, and
• and wherein Rc is, at each occurrence, independently a hydrogen atom or a C1-12 alkyl group;
• wherein B1 and B2 are each independently a linking bond or a C1-30 alkylene group;
• wherein R1 and R2 are each independently a C5-30 aliphatic group or
• wherein t is an integer from 0 to 12;
• wherein t1 and t2 are each independently an integer from 0 to 5;
• wherein;
• t3 and t4 are each 1;
• and wherein Re and Rf are each independently selected from the group consisting of a C1-15 alkyl group, a C2-15 alkenyl group, and a C2-15 alkynyl group;
• wherein R3 comprises H, —(CH2)tOH, —(CH)tSH, —OCH3, —OCH2CH3, —(CH2)tNH2, —(CH2)tC(═O)OH, —C(═O)(CH2)tC(═O)OH, —C(═O)CH3, —(CH2)tN3, —C(═O)CH2CH3, —C(═O)OCH3, —OC(═O)OCH3, —C(═O)OCH2CH3, —OC(═O)OCH2CH3, —(CH2)tN(CH3)2, —(CH2)tCHO,
• wherein t is an integer from 0 to 12;
• wherein A is —CH2CH2O— or —OCH2CH2—, and n is an integer from 2 to 6;
• and
• wherein said alkyl group, alkylene group, alkoxy group, and aliphatic hydrocarbon group are each independently substituted or unsubstituted.