Biodegradable compound, lipid particle, composition containing lipid particle, and kit

Patent metadata

Field	Value
Publication number	US-10639279-B2
Application number	US-201815918397-A
Country	US
Kind code	B2
Filing date	Mar 12, 2018
Priority date	Sep 13, 2017
Publication date	May 5, 2020
Grant date	May 5, 2020

Abstract

The compound according to the present embodiment is represented by the following formula (1):

Q-L-CHR 2   (1)

(wherein,
Q is a non-cationic aliphatic group that does not contain nitrogen but contains oxy; L is a single bond or an aliphatic group containing no nitrogen; Rs are C 12 -C 24 aliphatic group, the same or different; and at least one R contains, in the main chain or side chain thereof, a linking group L R selected from the group consisting of —C(═O)—O—, —O—C(═O)—, —O—C(═O)—O—, —S—C(═O)—, —C(═O)—S—, —C(═O)—NH—, and —NH—C(═O)—).

First claim

The invention claimed is:

1. A compound represented by the following formula (1):
Q-L-CHR 2   (1)

wherein,
Q is a non-cationic aliphatic group which is represented by the following formula (1B-1):
Q 0 -[(CH 2 ) b1 —O-] b2 -  (1B-1)

wherein
Q 0 is hydrogen, halogen, alkyl, or alkenyl;
b1 is a number from 0 to 3;
b2 is a number from 1 to 3; and
the total number of carbon atoms contained in the formula (1B-1) is 6 or less;

L is an aliphatic group which is represented by the following formula (1A):
-L A a -L 0 -L A a -  (1A)

wherein
L A is alkylene or cycloalkylene that is optionally substituted independently with oxygen;
L 0 is an ester structure selected from the group consisting of —C(═O)—O—, —O—C(═O)—, —O—C(═O)—O—, —S—C(═O)—, and —C(═O)—S—, and a is independently a number from 0 to 6);

Rs are C 12 -C 24 aliphatic groups, the same or different; and at least one R contains, in the main chain or side chain thereof, a linking group L R selected from the group consisting of —C(═O)—O—, —O—C(═O)—, —O—C(═O)—O—, —S—C(═O)—, —C(═O)—S—, —C(═O)—NH—, and —NH—C(═O)—.

2. The compound according to claim 1 , wherein the L contains an ester structure selected from the group consisting of —C(═O)—O—, —O—C(═O)—, —O—C(═O)—O—, —C(═S)—O—, —O—C(═S)—, —O—C(═S)—O—, —S—C(═O)—, and —C(═O) S—.

3. The compound according to claim 1 , wherein the Q is represented by the following formula (1B-2):
Q 1 -L B -  (1B-2)

wherein,
Q 1 is a cyclo ether; and
L B is alkylene.

4. The compound according to claim 1 , wherein the at least one R is represented by the following formula (1C):
-L C1 -C(═O)—O-L C2   (1C)

wherein,
L C1 is alkylene; and
L C2 is alkenyl.

5. The compound according to claim 4 , wherein the L C1 and the L C2 are represented by the following formulae (1C-1) and (1C-2) respectively:
—(CH 2 ) c1 -(1C-1)

—CH 2 —CH═CH—(CH 2 ) c2 —H(1C-2)

wherein
c1 is a number from 1 to 10; and
c2 is a number from 1 to 10.

6. The compound according to claim 5 , wherein the c1 is a number from 4 to 8.

7. The compound according to claim 1 , wherein the longest molecular chain contained in the R has 8 or more atoms.

8. The compound according to claim 1 , wherein is said compound is a compound presented by one of the following formulae (1-01), (1-02), (1-05) to (1-12), and (1-14) to (1-20)

9. A lipid particle comprising the compound according to claim 1 .

10. The lipid particle according to claim 9 , further comprising a membrane-forming lipid and an aggregation-reducing lipid.

11. The lipid particle according to claim 10 , wherein the membrane-forming lipid is selected from the group consisting of
1,2-dioleoyl-sn-glycero-3-phosphoethanol amine (DOPE),
1,2-stearoyl-sn-glycero-3-phosphoethanol amine (DSPE),
1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC),
1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC),
1,2-di-O-octadecyl-3-trimethylammonium propane (DOTMA),
1,2-dioleoyl-3-dimethylammonium propane (DODAP),
1,2-dimyristoyl-3-di methylammonium propane (14:0 DAP),
1,2-dipalmitoyl-3-dimethylammonium propane (16:0 DAP),
1,2-distearoyl-3-dimethylammonium propane (18:0 DAP),
N-(4-carboxybenzyl)-N,N-dimethyl-2,3-bis(oleoyloxy)propane (DOBAQ),
1,2-dioleoyl-3-trimethylammonium propane (DOTAP),
1,2-dioleoyl-sn-glycero-3-phosphochlorine (DOPC),
1,2-dilinoleoyl-sn-glycero-3-phosphochlorine (DLPC),
1,2-dioleoyl-sn-glycero-3-phospho-L-serine (DOPS), cholesterol, and the like; and
wherein the aggregation-reducing lipid is a polyethylene glycol (PEG)-modified lipid.

12. The lipid particle according to claim 9 , further comprising an active agent.

13. The lipid particle according to claim 12 , wherein the active agent is a nucleic acid selected from the group consisting of plasmids, oligonucleotides, polynucleotides, siRNAs, micro RNAs, DNAs, aptamers, and ribozymes.

14. The lipid particle according to claim 13 , further comprising a compound that binds to a nucleic acid.

15. The lipid particle according to claim 14 , wherein the compound that binds to a nucleic acid is a basic protein or a basic peptide.

16. The lipid particle according to claim 14 , wherein the compound that binds to a nucleic acid is a protamine or a histone.

17. The lipid particle according to claim 14 , further comprising a compound that regulates the expression of a nucleic acid in a cell.

18. A composition comprising the lipid particle according to claim 9 and a carrier.

19. A kit comprising the lipid particle according to claim 9 and a composition containing an incorporation agent for incorporating the lipid particle into a cell.

20. A compound represented by the following formula (1):
Q-L-CHR 2   (1)

wherein,
Q is a non-cationic aliphatic group that does not contain nitrogen but contains oxy;
L is a single bond or an aliphatic group containing no nitrogen;
Rs are C 12 -C 24 aliphatic groups, the same or different; and at least one R is represented by the following formula (1C):
—(CH 2 ) c1 —C(═O)—O—CH 2 —CH═CH—(CH 2 ) c2 —H  (1C)

wherein,
c1 is a number from 1 to 10; and
c2 is a number from 1 to 10.

21. The compound according to claim 20 , wherein the L contains an ester structure selected from the group consisting of —C(═O)—O—, —O—C(═O)—, —O—C(═O)—O—, —C(═S)—O—, —O—C(═S)—, —O—C(═S)—O—, —S—C(═O)—, and —C(═O) S—.

22. The compound according to claim 20 , wherein the L is represented by the following formula (1A):
-L A a -L 0 -L A a -  (1A)

wherein
L A is alkylene or cycloalkylene that is optionally substituted independently with oxygen;
L 0 is an ester structure selected from the group consisting of —C(═O)—O—, —O—C(═O)—, —O—C(═O)—O—, —S—C(═O)—, and —C(═O)—S—, and a is independently a number from 0 to 6.

23. The compound according to claim 22 , wherein the Q is represented by the following formula (1B-1):
Q 0 -[(CH 2 ) b1 —O—] b2 -  (1B-1)

wherein
Q 0 is hydrogen, halogen, alkyl, or alkenyl;
b1 is a number from 0 to 3;
b2 is a number from 1 to 3; and
the total number of carbon atoms contained in the formula (1B-1) is 6 or less.

24. The compound according to claim 22 , wherein the Q is represented by the following formula (1B-2):
Q 1 -L B -  (1B-2)

wherein,
Q 1 is a cyclo ether; and
L B is alkylene.

25. The compound according to claim 20 , wherein the c1 is a number from 4 to 8.

26. The compound according to claim 20 , wherein the longest molecular chain contained in the R has 8 or more atoms.

27. The compound according to claim 20 , wherein said compound is a compound presented by one of the following formulae (1-01) to (1-12) and (1-14) to (1-20)

Assignees

• Toshiba Kk

Inventors

• Ishihara Mitsuko
• Akahoshi Eiichi
• Naito Katsuyuki

Classifications

• A61K9/1275

  Lipoproteins or protein-free species thereof, e.g. chylomicrons; Artificial high-density lipoproteins [HDL], low-density lipoproteins [LDL] or very-low-density lipoproteins [VLDL]; Precursors thereof · CPC title

• A61K47/6911

  the form being a liposome · CPC title

• C07C69/732

  of unsaturated hydroxy carboxylic acids · CPC title

• C07F9/00

  Compounds containing elements of Groups 5 or 15 of the Periodic Table · CPC title

• C07C327/32

  having sulfur atoms of esterified thiocarboxyl groups bound to carbon atoms of hydrocarbon radicals substituted by carboxyl groups · CPC title