Cationic lipid for nucleic acid delivery

Patent metadata

Field	Value
Publication number	US-10092655-B2
Application number	US-201515504239-A
Country	US
Kind code	B2
Filing date	Aug 7, 2015
Priority date	Aug 18, 2014
Publication date	Oct 9, 2018
Grant date	Oct 9, 2018

Abstract

The invention provides a cationic lipid capable of achieving higher intracellular delivery efficiency than conventional cationic lipids, when used as a lipid membrane structure which is a carrier for delivering functional nucleic acid. The cationic lipid is represented by the formula (1):

wherein each symbol is as defined herein.

First claim

The invention claimed is:

1. A cationic lipid represented by the formula (1):

wherein any 4 of X 1 -X 6 are each independently a group represented by the formula (X a ), a group represented by the formula (X b ) or a hydroxyl group (provided that said 4 are not hydroxyl groups at the same time), and the remaining 2 are each independently a group represented by the formula (X c ) or a hydroxyl group (provided that said 2 are not hydroxyl groups at the same time))
—Y 1 —R 1   (X a )

wherein R 1 is an aliphatic hydrocarbon group having 8-22 carbon atoms or an acyl group having 8-22 carbon atoms; Y 1 is —O— or —NH—)

wherein R 2 is a sterol residue or a liposoluble vitamin residue; Z 1 is an alkylene group having 2 or 3 carbon atoms; Y 2 is —O—CO— or —NH—CO—)

wherein R 3 and R 4 are each independently an alkyl group having 1-6 carbon atoms, R 3 and R 4 are optionally bonded to form a ring; Z 2 is an alkylene group having 1-6 carbon atoms; Y 3 is —O—, —O—CO— or —NH—CO—; n is 0 or 1.

2. The cationic lipid according to claim 1 , wherein any 4 of X 1 -X 6 are each independently a group represented by the formula (X a ) or a group represented by the formula (X b ), and the remaining 2 are each independently a group represented by the formula (X c ).

3. The cationic lipid according to claim 1 , wherein any 4 of X 1 -X 6 are each independently a group represented by the formula (X a ), and the remaining 2 are each independently a group represented by the formula (X c ).

4. The cationic lipid according to claim 1 , wherein R 1 is an aliphatic hydrocarbon group having 10-20 carbon atoms or an acyl group having 10-20 carbon atoms.

5. The cationic lipid according to claim 1 , wherein R 1 is an aliphatic hydrocarbon group having an unsaturated bond and 10-20 carbon atoms or an acyl group having 10-20 carbon atoms.

6. The cationic lipid according to claim 1 , wherein Y 1 is —O—.

7. The cationic lipid according to claim 1 , wherein any 4 of X 1 -X 6 are each independently a group represented by the formula (X b ), and the remaining 2 are each independently a group represented by the formula (X c ).

8. A lipid membrane structure comprising the cationic lipid according to claim 1 .

9. A nucleic acid-introducing agent comprising the lipid membrane structure according to claim 8 and a nucleic acid.

Assignees

• Nof Corp
• Univ Hokkaido Nat Univ Corp

Inventors

• Sasaki Shota
• Ota Masaki
• Kubo Kazuhiro
• Harashima Hideyoshi
• Akita Hidetaka
• Hatakeyama Hiroto
• Noguchi Yuki
• Tange Kota
• Nakai Yuta
• Shimizu Nayuta

Classifications

• C07C229/12

  to carbon atoms of acyclic carbon skeletons · CPC title

• Y02P20/55

  Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups · CPC title

• A61K9/107

  Emulsions {; Emulsion preconcentrates; Micelles (composition of emulsions A61K47/00)} · CPC title

• A61K47/543 Primary

  Lipids, e.g. triglycerides; Polyamines, e.g. spermine or spermidine · CPC title

• A61K9/127

  Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant · CPC title