Ionizable lipid, preparation method thereof, and composition for preparing lipid nanoparticle

A composition for preparing a lipid nanoparticle, comprising:

• 30 to 75 parts by weight of an ionizable lipid;
• 5 to 20 parts by weight of a phospholipid compound;
• 19.5 to 60 parts by weight of a sterol compound;
• and
• 0.5 to 5 parts by weight of a polyethylene glycol lipid,
• wherein the ionizable lipid has a structure represented by the following formula (I):
• where Y is independently selected from a group consisting of —NH—, —O—, —S—, and a single bond;
• X is independently selected from —NR1R2 or a nitrogen-containing heteroaryl group;
• L1 and L2 are each independently selected from a group consisting of a C1-C10 alkylene group, a C2-C10 alkenylene group,
• R1 and R2 are each independently selected from a group consisting of H, a substituted or unsubstituted C1-C10 hydrocarbyl group, a substituted or unsubstituted C1-C10 heterohydrocarbyl group, a substituted or unsubstituted C6-C20 aryl group, and a substituted or unsubstituted C1-C20 heteroaryl group;
• R3 is a C5-C30 alkyl group;
• R4 is a C5-C30 alkyl group;
• n is an integer selected from 1 to 10;
• and
• m and p are each independently an integer selected from 1 to 20.

A preparation method of an ionizable lipid, comprising:

• forming an intermediate product from a diamine compound and a pan-lactone;
• mixing a carboxylic acid compound with the intermediate product to obtain a mixture;
• and
• esterifying the mixture to obtain the ionizable lipid,
• wherein the ionizable lipid has a structure represented by the following formula (II):
• where Y is independently selected from a group consisting of —NH—, —O—, —S—, and a single bond;
• L1 and L2 are each independently selected from a group consisting of a C1-C10 alkylene group, a C2-C10 alkenylene group,
• R1 and R2 are each independently selected from a group consisting of H, a substituted or unsubstituted C1-C10 hydrocarbyl group, a substituted or unsubstituted C1-C10 heterohydrocarbyl group, a substituted or unsubstituted C6-C20 aryl group, and a substituted or unsubstituted C1-C20 heteroaryl group;
• R3 is a C5-C30 alkyl group;
• R4 is a C5-C30 alkyl group;
• n is an integer selected from 1 to 10;
• and
• m and p are each independently an integer selected from 1 to 20.