Lipids, lipid complexes and use thereof
The present invention is related to a compound according to formula (I), wherein R 1 and R 2 are each and independently selected from the group comprising alkyl; n is any integer between 1 and 4; R 3 is an acyl selected from the group comprising lysyl, ornithyl, 2,4-diaminobutyryl, histidyl and an acyl moiety according to formula (II), wherein m is any integer from 1 to 3 and Y − is a pharmaceutically acceptable anion.
1. A composition comprising a pharmaceutically acceptable carrier and a compound according to formula (I),
wherein R 1 and R 2 are each and independently selected from the group comprising alkyl;
n is any integer between 1 and 4;
R 3 is an acyl selected from the group comprising lysyl, ornithyl, 2,4-diaminobutyryl, histidyl and an acyl moiety according to formula (II),
wherein m is any integer from 1 to 3 and
Y − is a pharmaceutically acceptable anion.
2. The composition according to claim 1 , wherein R 1 and R 2 are each and independently selected from the group comprising lauryl, myristyl, palmityl and oleyl.
3. The composition according to claim 1 , wherein R 1 is lauryl and R 2 is myristyl; or R 1 is palmityl and R 2 is oleyl.
4. The composition according to claim 1 , wherein m is 1 or 2.
5. The composition according to claim 1 , wherein Y − is selected from the group consisting of halogenids, acetate, and trifluoroacetate.
6. The composition according to claim 1 , wherein the compound is selected from the group consisting of:
7. The composition according to claim 1 , wherein the composition further comprises a pharmaceutically active component selected from the group consisting of peptides, proteins, oligonucleotides, polynucleotides, and nucleic acids.
8. The composition according to claim 7 , further comprising at least one helper lipid component selected from the group consisting of phospholipids and steroids.
9. The composition according to claim 8 , wherein the helper lipid component is selected from the group consisting of 1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine and 1,2-dioleyl-sn-glycero-3-phosphoethanolamine.
10. The composition according to claim 8 , wherein the content of the helper lipid component is from about 20 mol % to about 80 mol % of the overall lipid content of the composition.
11. The composition according to claim 8 , wherein at least one helper lipid comprises a moiety which is selected from the group consisting of a PEG, a HEG, a polyhydroxyethyl starch (polyHES), and a polypropylene.
12. The composition according to claim 11 , wherein the helper lipid comprising the PEG moiety is selected from the group consisting of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, 1,2-dialkyl-sn-glycero-3-phosphoethanolamine, and Ceramide-PEG.
13. The composition according to claim 1 , comprising:
a) 50 mol % of β-arginyl-2,3-diamino propionic acid-N-palmityl-N-oleyl-amide trihydrochloride,
48 mol % of 1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine, and
2 mol % 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-PEG2000; or
b) β-arginyl-2,3-diamino propionic acid-N-palmityl-N-oleyl-amide trihydrochloride,
49 mol % 1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine, and
1 mol % 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-PEG2000.
14. The composition according to claim 7 , wherein the oligonucleotide is siRNA or siNA.
15. The composition according to claim 1 , said composition comprising:
a) 50 mol % of β-arginyl-2,3-diamino propionic acid-N-palmityl-N-oleyl-amide trihydrochloride,
48 mol % of 1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine, and
2 mol % N(Carbonyl-methoxypolyethylenglycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine; or
b) 50 mol % of β-arginyl-2,3-diamino propionic acid-N-palmityl-N-oleyl-amide trihydrochloride,
49 mol % 1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine, and
1 mol % N(Carbonyl-methoxypolyethylenglycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine.
16. The composition according to claim 1 , said composition comprising:
a) 50 mol % of β-L-arginyl-2,3-L-diamino propionic acid-N-palmityl-N-oleyl-amide trihydrochloride,
48 mol % of 1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine, and
2 mol % N(Carbonyl-methoxypolyethylenglycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine; or
b) 50 mol % of β-L-arginyl-2,3-L-diamino propionic acid-N-palmityl-N-oleyl-amide trihydrochloride,
49 mol % 1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine, and
1 mol % N(Carbonyl-methoxypolyethylenglycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine.
17. The composition according to claim 16 , said composition further comprising siRNA or siNA as a pharmaceutically active component.