Lipid analogs and liposomes comprising same

Patent metadata

Field	Value
Publication number	US-10730976-B2
Application number	US-201616064498-A
Country	US
Kind code	B2
Filing date	Dec 22, 2016
Priority date	Dec 22, 2015
Publication date	Aug 4, 2020
Grant date	Aug 4, 2020

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, and a sphingolipid, and/or
b) 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.

2. The polymeric compound of claim 1 , wherein Y is a substituted or unsubstituted alkylene unit.

3. The polymeric compound of claim 2 , wherein Y has the formula —CR 4 R 5 —CR 6 D-, wherein:
when Y is a backbone unit which is not attached to said L or said Z, D is R 7 ; and when Y is a backbone unit which is attached to said L or said Z, D is a covalent bond or a linking group attaching Y to said L or said Z, said linking group being selected from the group consisting of —O—, —S—, alkylene, arylene, sulfinyl, sulfonyl, phosphate, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, urea, thiourea, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamido, and amino; and
R 4 -R 7 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, cyano, nitro, azide, azo, phosphate, phosphonyl, phosphinyl, oxo, carbonyl, thiocarbonyl, urea, thiourea, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamido, and amino.

4. The polymeric compound of claim 1 , wherein A is a substituted or unsubstituted hydrocarbon from 1 to 4 carbon atoms in length.

5. The polymeric compound of claim 1 , wherein n is at least 3.

6. The polymeric compound of claim 1 , wherein at least a portion of said Y, said L and/or said Z comprise at least one targeting moiety.

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

8. The polymeric compound of claim 1 , wherein X has said general formula III.

9. The polymeric compound of claim 8 , wherein at least one of W 1 and W 2 is alkyl, alkenyl, alkynyl or acyl, being from 10 to 30 carbon atoms in length.

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

11. A liposome comprising at least one lipid bilayer according to claim 10 .

12. The liposome of claim 11 , further comprising at least one functional moiety or agent, bound to a surface of the liposome and/or within a lipid bilayer and/or core of the liposome.

13. A lubricant composition comprising liposomes according to claim 11 and a carrier.

14. The lubricant composition of claim 13 , being for lubricating a physiological surface, wherein said carrier is a physiologically acceptable carrier.

15. A method of reducing a friction coefficient of a surface, the method comprising contacting the surface with liposomes according to claim 11 .

16. The method of claim 15 , further comprising contacting the surface with a water-soluble polymer.

17. The method of claim 15 , wherein said surface is a physiological surface, the method being effected by contacting the surface with a composition comprising said liposomes and a physiologically acceptable carrier.

18. A method of treating a synovial joint disorder associated with an increased friction coefficient of an articular surface in the synovial joint in a subject in need thereof, the method comprising administering to the subject the liposome of claim 11 .

19. A method of inhibiting biofilm formation on a surface of a substrate, the method comprising contacting the substrate with a composition which comprises liposomes according to claim 11 .

20. An article of manufacture comprising a composition-of-matter, the composition-of-matter comprising a substrate coated, on at least a portion of a surface thereof, by a lipid bilayer according to claim 10 .

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