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 preparation comprising one or more compounds, each individually having a structure defined by formula (I) or a pharmaceutically acceptable salt thereof,
wherein
each X a and X b , for each occurrence, is independently C 1-6 alkylene;
n is 0, 1, 2, 3, 4 or 5; each R is independently H,
wherein at least n+2 of the R moieties in at least about 80% of the molecules of the compound of formula (I) in the preparation are not H;
m is 1, 2, 3 or 4; Y is O, NR 2 , or S;
R 1 is alkyl, alkenyl or alkynyl; each of which is optionally substituted with one or more substituents; and
R 2 is H, alkyl, alkenyl or alkynyl, each of which is optionally substituted with one or more substituents;
provided that, if n=0, then at least n+3 of the R moieties are not H.
2 . A compound of formula (X),
wherein
R 1 and R 2 are each independently H, C 1 -C 6 alkyl, optionally substituted with 1-4 R 5 , C 2 -C 6 alkenyl, optionally substituted with 1-4 R 5 , or C(NR 6 )(NR 6 ) 2 ;
R 3 and R 4 are each independently alkyl, alkenyl, alkynly, each of which is optionally substituted with fluoro, chloro, bromo, or iodo;
L 1 and L 2 are each independently —NR 6 C(O)—, —C(O)NR 6 —, —OC(O)—, —C(O)O—, —S—S—, —N(R 6 )C(O)N(R 6 )—, —OC(O)N(R 6 )—, —N(R 6 )C(O)O—, —O—N═C—, OR, —OC(O)NH—N═C—, or —NHC(O)NH—N═C—,
L 1 -R 3 and L 2 -R 4 can be taken together to form an acetal, a ketal, or an orthoester, wherein R 3 and R 4 are defined as above and can also be H or phenyl;
R 5 is fluoro, chloro, bromo, iodo, —OR 7 , —N(R 8 )(R 9 ), —CN, SR 10 , S(O)R 10 , S(O) 2 R 10
R 6 is H, C 1 -C 6 alkyl,
R 7 is H or C 1 -C 6 alkyl;
each R 8 and R 9 are independently H or C 1 -C 6 alkyl;
R 10 is H or C 1 -C 6 alkyl;
m is 1, 2, 3, 4, 5, or 6;
n is 0, 1, 2, 3, 4, 5, or 6;
or a pharmaceutically acceptable salt thereof.
3 . A preparation comprising a compound of claim 2 .
4 . An association complex comprising a preparation of claim 1 .
5 . An association complex comprising a preparation of claim 3 .
6 . The association complex of claim 4 , further comprising a therapeutic agent.
7 . The association complex of claim 6 , wherein the therapeutic agent is nucleic acid.
8 . The association complex of claim 6 , wherein the therapeutic agent is siRNA.
9 . The association complex of claim 6 , wherein the therapeutic agent is mRNA.
10 . The association complex of claim 5 , further comprising a therapeutic agent.
11 . The association complex of claim 10 , wherein the therapeutic agent is nucleic acid.
12 . The association complex of claim 10 , wherein the therapeutic agent is siRNA.
13 . The association complex of claim 10 , wherein the therapeutic agent is mRNA.
14 . A method of treating a mammal comprising administering to said mammal a therapeutic amount of an association complex of claim 6 .
15 . A method of treating a mammal comprising administering to said mammal a therapeutic amount of an association complex of claim 10 .
16 . A compound of formula (XV):
wherein;
each L 1 and L 2 are independently a bond or C(O);
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 alkylC(O)NH—; or —C(O)C 1-3 alkylC(O)O—;
m is an integer from 0-11 and
n is an integer from 1-500.