Antimicrobial cationic polycarbonates

Patent metadata

Field	Value
Publication number	US-9631050-B2
Application number	US-201615154948-A
Country	US
Kind code	B2
Filing date	May 14, 2016
Priority date	Apr 9, 2013
Publication date	Apr 25, 2017
Grant date	Apr 25, 2017

Abstract

Antimicrobial cationic polymers having one or two cationic polycarbonate chains were prepared by organocatalyzed ring opening polymerization. One antimicrobial cationic polymer has a polymer chain consisting essentially of cationic carbonate repeat units linked to one or two end groups. The end groups can comprise a covalently bound form of biologically active compound such as cholesterol. Other antimicrobial cationic polymers have a random copolycarbonate chain comprising a minor mole fraction of hydrophobic repeat units bearing a covalently bound form of a vitamin E and/or vitamin D2. The cationic polymers exhibit high activity and selectivity against Gram-negative and Gram-positive microbes and fungi.

First claim

What is claimed is:

1. An antimicrobial cationic polymer of formula (12):
Z c —P b —C′—P b —Z c   (12),

wherein
C′ is a C 2 -C 15 divalent linking group joining polymer chains P b , wherein C′ comprises i) a first heteroatom linked to a first polymer chain P b , wherein the first heteroatom is selected from the group consisting of nitrogen, oxygen, and sulfur, and ii) a second heteroatom linked to a second polymer chain P b , wherein the second heteroatom is selected from the group consisting of nitrogen, oxygen, and sulfur,
each Z c is an independent monovalent end group selected from the group consisting of hydrogen and C 1 -C 15 moieties,
each polymer chain P b consists essentially of cationic carbonate repeat units, wherein i) the cationic polymer comprises a total of 5 to about 45 cationic carbonate repeat units, ii) each of the cationic carbonate repeat units comprises a) a backbone portion of the polymer chain comprising an aliphatic carbonate group, and b) a cationic side chain linked to the backbone portion, and iii) the cationic side chain comprises a positive-charged heteroatom Q′ of a quaternary ammonium group and/or quaternary phosphonium group,
about 25% to 100% of all the cationic carbonate repeat units of the cationic polymer, designated first cationic carbonate repeat units, have a structure selected from the group consisting of

and combinations thereof, wherein X − is a negative-charged ion, and
0% to about 75% of the cationic carbonate repeat units of the cationic polymer, designated second cationic carbonate repeat units, have a cationic side chain comprising 6 to 9 carbons.

2. The cationic polymer of claim 1 , wherein the second cationic carbonate repeat units have a cationic side chain comprising 6 to 12 carbons.

3. The cationic polymer of claim 1 , wherein the first cationic repeat units have the structure

4. The cationic polymer of claim 1 , wherein the first cationic repeat units have the structure

5. The cationic polymer of claim 1 , wherein the first cationic carbonate repeat units have the structure

6. The cationic polymer of claim 1 , wherein the first cationic repeat units have the structure

7. The cationic polymer of claim 1 , wherein the cationic polymer is effective in killing a microbe selected from the group consisting of Staphylococcus epidermidis ( S. epidermidis ), Staphylococcus aureus ( S. aureus ), Escherichia coli ( E. coli ), Pseudomonas aeruginosa ( P. aeruginosa ), Candida albicans ( C. albicans ), Methicillin-resistant Staphylococcus aureus (MRSA), Vancomycin-resistant Enterococcus (VRE), Acinetobacter baumannii ( A. baumannii ), Cryptococcus neoformans ( C. neoformans ), Klebsiella pneumoniae ( K. pneumoniae ), and combinations thereof.

8. An antimicrobial cationic polymer of formula (14):
Z c —P b —C″—P b —Z c   (14),

wherein
C″ is a divalent linking group joining polymer chains P b , wherein C″ comprises i) a first heteroatom linked to a first polymer chain P b , wherein the first heteroatom is selected from the group consisting of nitrogen, oxygen, and sulfur, ii) a second heteroatom linked to a second polymer chain P b , wherein the second heteroatom is selected from the group consisting of nitrogen, oxygen, and sulfur, and iii) a covalently bound form of a compound selected from the group consisting of steroids, non-steroid hormones, vitamins, and drugs,
each Z c is an independent monovalent end group selected from the group consisting of hydrogen and C 1 -C 15 moieties,
each polymer chain P b consists essentially of cationic carbonate repeat units, wherein i) the cationic polymer comprises a total of 5 to about 45 cationic carbonate repeat units, ii) each of the cationic carbonate repeat units comprises a) a backbone portion of the polymer chain comprising an aliphatic carbonate group, and b) a C 6 -C 25 cationic side chain linked to the backbone portion, and iii) the cationic side chain comprises a positive-charged heteroatom Q′ of a quaternary ammonium group and/or quaternary phosphonium group,
about 25% to 100% of the cationic carbonate repeat units of the cationic polymer, designated first cationic carbonate repeat units, have a structure selected from the group consisting of

and combinations thereof, wherein X − is a negative-charged ion, and
0% to about 75% of the cationic carbonate repeat units of the cationic polymer, designated second cationic carbonate repeat units, have a cationic side chain group comprising 6 to 9 carbons.

9. The cationic polymer of claim 8 , wherein C″ comprises a cholesteryl group.

10. The cationic polymer of claim 8 , wherein C″ comprises a covalently bound form of vitamin.

11. The cationic polymer of claim 8 , wherein the vitamin is selected from the group consisting of vitamin E compounds, vitamin D compounds, and combinations thereof.

12. An antimicrobial cationic random copolymer of formula (16):
Z c —P c —C′—P c —Z c   (16),

wherein
C′ is a C 2 -C 15 divalent linking group joining polymer chains P b , wherein C′ comprises i) a first heteroatom linked to a first polymer chain P b , wherein the first heteroatom is selected from the group consisting of nitrogen, oxygen, and sulfur, and ii) a second heteroatom linked to a second polymer chain P b , wherein the second heteroatom is selected from the group consisting of nitrogen, oxygen, and sulfur,
each Z c is an independent monovalent end group selected from the group consisting of hydrogen and C 1 -C 15 moieties,
each P c is a polymer chain consisting essentially of I) about 85 mol % to 99.9 mol % of cationic carbonate repeat units, and II) 0.1 mol % to about 15 mol % of a carbonate repeat unit comprising a covalently bound form of a steroid and/or a vitamin compound, designated H′, wherein i) the cationic polymer has a total number of repeat units of about 5 to about 45, ii) each of the cationic carbonate repeat units comprises a) a polymer backbone portion comprising an aliphatic carbonate group, and b) a C 6 -C 25 cationic side chain portion linked to the polymer backbone portion, and iii) each cationic side chain portion comprises a positive-charged heteroatom Q′ of a quaternary ammonium group and/or quaternary phosphonium group,
about 25% to 100% of the cationic carbonate repeat units of the cationic polymer, designated first cationic carbonate repeat units, have a structure selected from the group consisting of

and combinations thereof, wherein X − is a negative-charged ion, and
0% to about 75% of the cationic carbonate repeat units of the cationic polymer, designated second cationic carbonate repeat units, have a cationic side chain group comprising 6 to 9 carbons.

13. The random copolymer of claim 12 , wherein H′ is a covalently bound form of alpha-tocopherol.

14. The random copolymer of claim 12 , wherein H′ is a covalently bound form of ergocalciferol.

15. An antimic

Assignees

• IBM
• Agency Science Tech & Res

Inventors

• Coady Daniel J
• Dipietro Richard A
• Engler Amanda C
• Hedrick James L
• Ng Victor W L
• Ong Zhan-Yuin
• Tan Jeremy P K
• Yang Yi Yan

Classifications

• A01N43/50 Primary

  1,3-Diazoles; Hydrogenated 1,3-diazoles · CPC title

• C08G64/0233

  containing halogens · CPC title

• A01N33/12

  Quaternary ammonium compounds · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• A01N57/34

  having phosphorus-to-halogen bonds; Phosphonium salts · CPC title