Cationic lipids and preparation method thereof
The present invention provides cationic lipids and lipid nanoparticle formulations comprising these lipids, alone or in combination with other lipids. These lipid nanoparticles may be formulated with nucleic acids to facilitate their intracellular delivery both in vitro and for therapeutic applications. The present invention also provides methods of chemical synthesis of these lipids.
1 . A cationic lipid, or a salt, hydrate, solvate, polymorph, optical isomer, geometrical isomer, enantiomer, diastereomer, tautomer, isotope labeled compound or mixtures thereof, wherein the cationic lipid is represented by the structure of formula (IV):
wherein
R 1 -L- is
R 2 and R 3 are each independently C p alkylene-Z—C q alkyl;
Z, at each occurrence, is independently —O—C(═O)— or —C(═O)—O—;
p, at each occurrence, is independently an integer selected from 4, 5, 6, 7, 8, 9, or 10; and
q, at each occurrence, is independently an integer selected from 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22.
2 . The cationic lipid according to claim 1 , or a salt, hydrate, solvate, polymorph, optical isomer, geometrical isomer, enantiomer, diastereomer, tautomer, isotope labeled compound or mixtures thereof, wherein said cationic lipid has the following structure:
3 . The cationic lipid according to claim 1 , or a salt, hydrate, solvate, polymorph, optical isomer, geometrical isomer, enantiomer, diastereomer, tautomer, isotope labeled compound or mixtures thereof, wherein said cationic lipid has the following structure:
4 . A nanoparticle composition, comprising the cationic lipid according to claim 1 , or a salt, hydrate, solvate, polymorph, optical isomer, geometrical isomer, enantiomer, diastereomer, tautomer, isotope labeled compound or mixtures thereof.
5 . The nanoparticle composition of claim 4 ,
wherein said cationic lipid has the following structure:
6 . The nanoparticle composition of claim 4 , wherein said cationic lipid has the following structure:
7 . A pharmaceutical composition comprising the cationic lipid according to claim 1 , or a salt, hydrate, solvate, polymorph, optical isomer, geometrical isomer, enantiomer, diastereomer, tautomer, isotope labeled compound or mixtures thereof, and a pharmaceutically acceptable carrier.
8 . The pharmaceutical composition of claim 7 , wherein said cationic lipid has the following structure:
9 . The pharmaceutical composition of claim 7 , wherein said cationic lipid has the following structure:
10 . A pharmaceutical composition comprising the nanoparticle composition according to claim 4 and a pharmaceutically acceptable carrier.
11 . The pharmaceutical composition of claim 10 , wherein said cationic lipid has the following structure:
12 . The pharmaceutical composition of claim 10 , wherein said cationic lipid has the following structure: