Lipid analogs and liposomes comprising same

Patent metadata

Field	Value
Publication number	US-11396563-B2
Application number	US-202016919138-A
Country	US
Kind code	B2
Filing date	Jul 2, 2020
Priority date	Dec 22, 2015
Publication date	Jul 26, 2022
Grant date	Jul 26, 2022

Abstract

A polymeric compound is disclosed herein, having the general formula I:

wherein m, n, X, Y, Z and L are as defined herein. Further disclosed herein are lipid bilayers comprising at least one bilayer-forming lipid and the aforementioned polymeric compound, and liposomes comprising such a bilayer, as well as methods, uses and compositions utilizing such bilayers and/or liposomes for reducing a friction coefficient of a surface and/or for inhibiting biofilm formation.

First claim

What is claimed is:

1. A polymeric compound having the general formula I:

wherein:
m is zero or a positive integer;
n is an integer which is at least 1, wherein when X does not comprise a phosphate group, n is at least 2;
X is a lipid moiety;
Y is a backbone unit which forms a polymeric backbone;
L is absent or is a linking moiety; and
Z has the general formula II:

wherein:
A is a substituted or unsubstituted hydrocarbon;
B is an oxygen atom or is absent; and
R 1 -R 3 are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, heteroalicyclic, aryl and heteroaryl,
and wherein:
a) said lipid is selected from the group consisting of a fatty acid, a monoglyceride, a glycerophospholipid, a sphingolipid, and a sterol; and/or
b) said lipid moiety comprises at least one fatty acid moiety selected from the group consisting of lauroyl, myristoyl, palmitoyl, and stearoyl.

2. The polymeric compound of claim 1 , wherein n is in a range of from 5 to 50, and m is in a range of from 0 to 50.

3. The polymeric compound of claim 1 , having the general formula Ib:

wherein:
T is a unit of said Y which comprises at least one targeting moiety;
X and T are attached to distal termini of the polymeric compound; and
X, Y, L, Z, n and m are as defined for general formula I, with the proviso that m is a positive integer.

4. The polymeric compound of claim 1 , wherein said lipid is selected from the group consisting of a fatty acid, a monoglyceride, a glycerophospholipid, a sphingolipid, and a sterol.

5. The polymeric compound of claim 4 , wherein said glycerophospholipid is selected from the group consisting of a phosphatidyl ethanolamine, a phosphatidyl serine, a phosphatidyl glycerol and a phosphatidyl inositol.

6. The polymeric compound of claim 1 , wherein X has the general formula III:

wherein:
W 1 and W 2 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl and acyl, wherein at least one of W 1 and W 2 is not hydrogen;
J is —P(═O)(OH)—O— or absent;
K is a substituted or unsubstituted hydrocarbon from 1 to 10 carbon atoms in length;
M is a linking group selected from the group consisting of —O—, —S—, amino, sulfinyl, sulfonyl, phosphate, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, urea, thiourea, carbamyl, thiocarbamyl, amido, carboxy, and sulfonamide, or absent; and
Q is a substituted or unsubstituted hydrocarbon from 1 to 10 carbon atoms in length, or absent,
wherein when M is absent, Q is also absent.

7. The polymeric compound of claim 6 , wherein J is —P(═O)(OH)—O— and K is selected from the group consisting of an ethanolamine moiety, a serine moiety, a glycerol moiety and an inositol moiety.

8. The polymeric compound of claim 6 , wherein M is amido.

9. The polymeric compound of claim 6 , wherein Q is dimethylmethylene (—C(CH 3 ) 2 —).

10. The polymeric compound of claim 6 , wherein J, M and Q are each absent.

11. The polymeric compound of claim 10 , wherein K is —C(═O)—C(CH 3 ) 2 —.

12. The polymeric compound of claim 1 , wherein said lipid moiety comprises at least one fatty acid moiety selected from the group consisting of lauroyl, myristoyl, palmitoyl, and stearoyl.

13. A lipid bilayer comprising at least one bilayer-forming lipid and the polymeric compound of claim 1 .

14. The lipid bilayer of claim 13 , wherein a molar ratio of said bilayer-forming lipid and said polymeric compound is in a range of from 5:1 to 5,000:1.

15. A liposome comprising at least one lipid bilayer according to claim 13 .

16. A method of reducing a friction coefficient of a surface, the method comprising contacting the surface with liposomes according to claim 15 .

17. The method of claim 16 , being effected by contacting the surface with a composition comprising said liposomes and a carrier which comprises an aqueous liquid.

18. The method of claim 16 , wherein said surface is a hydrogel surface.

19. The method of claim 16 , wherein said surface is a contact lens surface.

20. The method of claim 17 , wherein said surface is an articular surface of a synovial joint, and said carrier is a physiologically acceptable carrier.

Assignees

• Yeda Res & Dev

Inventors

• Klein Jacob
• Lin Weifeng
• Goldberg Ronit

Classifications

• C08F2438/01

  Atom Transfer Radical Polymerization [ATRP] or reverse ATRP · CPC title

• C08F130/02 Primary

  containing phosphorus · CPC title

• C07F9/11

  with hydroxyalkyl compounds without further substituents on alkyl · CPC title

• A61K47/6911

  the form being a liposome · CPC title

• A61K47/58

  obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin · CPC title