Cationic lipids for therapeutic agent delivery formulations

Patent metadata

Field	Value
Publication number	US-9963424-B2
Application number	US-201615005569-A
Country	US
Kind code	B2
Filing date	Jan 25, 2016
Priority date	Jun 8, 2011
Publication date	May 8, 2018
Grant date	May 8, 2018

Abstract

Here described are compounds of formula I:

wherein R 1 and R 2 are independently selected from C 10 to C 18 alkyl, C 12 to C 18 alkenyl, and oleoyl; R 3 and R 4 are independently selected from C 1 to C 6 alkyl and C 2 to C 6 alkanol; X is selected from —CH 2 —, —S—, and —O—, or X is absent; Y is selected from —(CH 2 ) n , —S(CH 2 ) n —, —O(CH 2 ) n —, -thiophene-, —SO 2 (CH 2 ) n —, and ester; n=1-4; a=1-4; b=1-4; c=1-4; and Z − is a counterion. Also described herein are compositions and pharmaceutical formulations including compounds of formula I which are useful for the delivery of therapeutic agents, and methods of using these compositions and formulations.

First claim

What is claimed:

1. A composition comprising a retinoid and/or retinoid conjugate, and a cationic lipid of formula I

wherein
R 1 and R 2 are independently selected from C 10 to C 18 alkyl, C 12 to C 18 alkenyl, and oleoyl;
R 3 and R 4 are independently selected from C 1 to C 6 alkyl and C 2 to C 6 alkanol;
X is selected from —CH 2 —, —S—, and —O—, or X is absent;
Y is selected from —(CH 2 ) n —, —S(CH 2 ) n —, —O(CH 2 ) n —, -thiophene-, —SO 2 (CH 2 ) n —, and -ester-;
n=1-4;
a=1-4; b=1-4; c=1-4; and
Z − is a counterion.

2. The composition of claim 1 , wherein the composition is a liposomal composition.

3. The composition of claim 1 , wherein the retinoid conjugate comprises a retinoid-linker-retinoid molecule and/or a retinoid-linker-lipid molecule.

4. The composition of claim 3 , wherein the linker comprises a PEG moiety.

5. The composition of claim 3 , wherein the retinoid-linker-retinoid molecule comprises a compound of formula II:

wherein q, r, and s are each independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; or an enantiomer, diastereomer, or mixture of stereoisomers thereof.

6. The composition of claim 5 , wherein the retinoid-linker-retinoid molecule is

7. The composition of claim 1 , wherein the cationic lipid is at a concentration of 5 mol % to 50 mol %.

8. The composition of claim 1 , wherein the cationic lipid is selected from the group consisting of

9. The composition of claim 8 , wherein the cationic lipid is

10. The composition of claim 1 , wherein the composition further comprises a PEG-lipid.

11. The composition of claim 10 , wherein the PEG-lipid is at a concentration of 1 to 10 mol %.

12. The composition of claim 1 , wherein the composition further comprises an ionizable cationic lipid.

13. The composition of claim 12 , wherein the ionizable cationic lipid is

14. The composition of claim 12 , wherein the ionizable cationic lipid is present at a concentration of 5 to 45 mol %.

15. The composition of claim 1 , wherein the composition further comprises a non-cationic lipid.

16. The composition of claim 15 , wherein the non-cationic lipid comprises a phospholipid and/or cholesterol.

17. The composition of claim 1 , further comprising a drug.

18. The composition of claim 17 , wherein the drug is a nucleic acid.

Assignees

• Nitto Denko Corp

Inventors

• Niitsu Yoshiro
• Knopov Victor
• Payne Joseph E
• Hou Zheng
• Gaudette John A
• Akopian Violetta
• Witte Richard P
• Ahmadian Mohammad
• Perelman Loren A
• Tanaka Yasunobu
• Karmali Priya
• Nagarajan Sridhar C

Classifications

• A61K9/0019 Primary

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61K9/10

  Dispersions; Emulsions · CPC title

• C07C333/04

  having nitrogen atoms of thiocarbamic groups bound to hydrogen atoms or to acyclic carbon atoms · CPC title

• A61K9/1271

  Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers (liposomes as conjugates {A61K47/6911}) · CPC title

• C07C237/08 Primary

  having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms · CPC title