Lipid containing formulations
Compositions and methods useful in administering nucleic acid based therapies, for example association complexes such as liposomes and lipoplexes are described.
1. A compound having the formula (XV):
wherein
L 1 and L 2 are both a bond;
each R 1 and R 2 are independently alkyl, alkenyl, or alkynyl, each of which is optionally substituted with one or more substituents;
X is —C(O)NH—, C(S)NH, —C(O)—C 1-3 alkyl-C(O)NH—, or —C(O)—C 1-3 alkyl-C(O)O—;
m is an integer from 0-11; and
n is an integer from 1-500.
2. The compound of claim 1 , wherein R 1 and R 2 are independently unsubstituted C 6 -C 28 alkyl.
3. The compound of claim 1 , wherein R 1 and R 2 are independently unsubstituted C 10 -C 18 alkyl.
4. The compound of claim 1 , wherein the substituents for R 1 and R 2 are selected from alkyl, cycloalkyl, haloalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, alkenyl, alkynyl, cycloalkenyl, heterocycloalkenyl, alkoxy, haloalkoxy, halo, hydroxy, carboxy, carboxylate, cyano, nitro, amino, alkyl amino, SO 3 H, sulfate, phosphate, methylenedioxy (—O—CH 2 —O— wherein oxygens are attached to same carbon (geminal substitution) atoms), ethylenedioxy, oxo, thioxo, imino, S(O) n alkyl (where n of S(O) n alkyl is 0-2), S(O) n aryl (where n of S(O), n aryl is 0-2), S(O) n heteroaryl (where n of S(O) n heteroaryl is 0-2), S(O) n heterocyclyl (where n of S(O) n heterocyclyl is 0-2), amine, ester, amide, and sulfonamide.
5. A compound having the formula
wherein
L 1 and L 2 are both a bond;
each R 1 and R 2 are independently alkyl, alkenyl, or alkynyl; each of which is optionally substituted with one or more substituents;
m is an integer from 0-11 and
n is an integer from 1-500.
6. The compound of claim 5 , wherein the substituents for R 1 and R 2 are selected from alkyl, cycloalkyl, haloalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, alkenyl, alkynyl, cycloalkenyl, heterocycloalkenyl, alkoxy, haloalkoxy, halo, hydroxy, carboxy, carboxylate, cyano, nitro, amino, alkyl amino, SO 3 H, sulfate, phosphate, methylenedioxy (—O—CH 2 —O— wherein oxygens are attached to same carbon (geminal substitution) atoms), ethylenedioxy, oxo, thioxo, imino, S(O) n alkyl (where n of S(O) n alkyl is 0-2), S(O) n aryl (where n of S(O) n aryl is 0-2), S(O) n heteroaryl (where n of S(O) n heteroaryl is 0-2), S(O) n heterocyclyl (where n of S(O) n heterocyclyl is 0-2), amine, ester, amide, and sulfonamide.
7. The compound of claim 5 , wherein R 1 and R 2 are independently unsubstituted C 6 -C 28 alkyl.
8. The compound of claim 5 , wherein R 1 and R 2 are independently unsubstituted C 10 -C 18 alkyl.
9. The compound of claim 7 , wherein R 1 and R 2 are straight chain alkyl having the same length.
10. The compound of claim 8 , wherein R 1 and R 2 are straight chain alkyl having the same length.
11. The compound of claim 5 , wherein R 1 and R 2 are unsubstituted C 14 alkyl.
12. The compound of claim 5 , wherein R 1 and R 2 are unsubstituted C 18 alkyl.
13. The compound of claim 5 , wherein m is 2.
14. The compound of claim 5 , wherein n is from 40 to 400.
15. The compound of claim 5 , wherein n is from 40 to 50.
16. The compound of claim 5 , wherein n is from 42 to 47.
17. The compound of claim 5 , wherein L 1 and L 2 are both bonds, R 1 and R 2 are both alkyl, and n is an integer from about 40-400.
18. The compound of claim 17 , wherein R 1 and R 2 are unsubstituted C 6 -C 28 alkyl.
19. The compound of claim 17 , wherein R 1 and R 2 are unsubstituted C 10 -C 18 alkyl.
20. The compound of claim 17 , wherein R 1 and R 2 are unsubstituted C 14 alkyl.
21. The compound of claim 5 , wherein the compound has the formula:
wherein each R is C 14 H 29 and n is from 42 to 47.
22. The compound of claim 21 , wherein the average molecular weight of the PEG moiety is 2000.
23. The compound of claim 5 , wherein the compound has the formula:
wherein each R is C 18 H 37 and n is from 42 to 47.
24. The compound of claim 23 , wherein the average molecular weight of the PEG moiety is 2000.
25. The compound of claim 5 , wherein the compound has the formula:
wherein n is an integer from 1-500.
26. The compound of claim 25 , wherein n is between 42 and 47.
27. A lipid particle comprising a compound of claim 5 .
28. The compound of claim 1 , wherein, each of R 1 and R 2 are independently C 6 -C 28 alkyl or C 6 -C 30 alkenyl and X is —C(O)NH—.