Arginine-based antibacterial polymers with UCST property

Patent metadata

Field	Value
Publication number	US-11827747-B2
Application number	US-202017609155-A
Country	US
Kind code	B2
Filing date	May 6, 2020
Priority date	May 6, 2019
Publication date	Nov 28, 2023
Grant date	Nov 28, 2023

Abstract

The present invention concerns a polymer comprising repetitive units having the following formula (I) wherein R 1 is H or Me; L is a linker; R 2 is the side chain of an α-amino acid being other than arginine; m is 0 or an integer comprised from 1 to 10; n is an integer comprised from 1 to 10; and X— is a counterion.

First claim

The invention claimed is:

1. A polymer comprising repetitive units having the following formula (I):

wherein:
R 1 is H or Me;
L is a linker;
R 2 is the side chain of an α-amino acid being other than arginine;
m is 0 or an integer comprised from 1 to 10;
n is an integer comprised from 1 to 10; and
X − is a counterion.

2. The polymer of claim 1 , wherein L is a linker having the following formula (II):
-A 1 -A 2 -A 3 -  (II)

wherein:
A 1 is a (C 1 -C 6 )alkylene group;
A 2 is a group obtained by alkyne-azide cycloaddition reaction; and
A 3 is a (C 1 -C 10 )alkylene group, optionally interrupted by one or several oxygen atoms.

3. The polymer of claim 2 , wherein A 2 is a triazole group.

4. The polymer of claim 1 , wherein L has the following formula:

5. The polymer of claim 1 , wherein m=0.

6. The polymer of claim 5 , further comprising repetitive units having the following formula (IV):

wherein:
p is an integer comprised from 1 to 10.

7. The polymer of claim 1 , having the following formula (V):

wherein:
R 1 , L, R 2 , X − , m, and n are as defined in claim 1 ;
R 3 represents an aliphatic or aromatic chain, optionally substituted by one or several functional groups and/or optionally interrupted by one or several oxygen atoms;
R 4 represents a group —S—C(═S)—Z, Z being the group controlling the reactivity of the C═S bond; and
q is comprised from 2 to 100.

8. The polymer of claim 6 , having the following formula (VI):

wherein:
R 3 represents an aliphatic or aromatic chain, optionally substituted by one or several functional groups and/or optionally interrupted by one or several oxygen atoms;
R 4 represents a group —S—C(═S)—Z, Z being the group controlling the reactivity of the C═S bond;
q is comprised from 2 to 100; and
r is comprised from 2 to 100.

9. The polymer of claim 1 , having the following formula (VII):

wherein:
L, R 2 , X − , m, and n are as defined in claim 1 , and
q is comprised from 2 to 100.

10. The polymer of claim 1 , having the following formula (VIII):

wherein:
X − and n are as defined in claim 1 ; and
q is comprised from 2 to 100.

11. A method for the preparation of a polymer of claim 1 , comprising a step of RAFT polymerization of a monomer having the following formula (IX):

wherein R 1 , L, R 2 , X − , m, and n are as defined in claim 1 .

12. The method of claim 11 , wherein m is 0, and comprising a step of RAFT polymerization of monomers having the following formulae (X) and (XI):

wherein p is an integer comprised from 1 to 10.

13. A monomer having one of the following formulae (IX) or (X):

wherein R 1 , L, R 2 , X − , m, and n are as defined in claim 1 .

14. A method for delivering a drug to a subject in need thereof, comprising
encapsulating the drug with the polymer of claim 1 , and
delivering the drug to the subject.

15. A method for treating a bacterial infection in a patient in need thereof, comprising
administering to the patient a pharmaceutically acceptable amount of the polymer of claim 1 .

Assignees

• Centre Nat Rech Scient
• Inst Nat Sante Rech Med
• Univ Strasbourg

Inventors

• Boulmedais Fouzia
• Chan-Seng Delphine
• Zydziak Nicolas
• Lavalle Philippe

Classifications

• C08G69/10 Primary

  Alpha-amino-carboxylic acids {(polysuccinimides C08G73/1092)} · CPC title

• C08G69/46

  Post-polymerisation treatment · CPC title

• C08F299/024

  the unsaturation being in acrylic or methacrylic groups · CPC title

• C08G69/06

  Solid state polycondensation · CPC title

• C08F2438/03

  Use of a di- or tri-thiocarbonylthio compound, e.g. di- or tri-thioester, di- or tri-thiocarbamate, or a xanthate as chain transfer agent, e.g . Reversible Addition Fragmentation chain Transfer [RAFT] or Macromolecular Design via Interchange of Xanthates [MADIX] · CPC title