Polycationic amphiphiles as antimicrobial agents

Patent metadata

Field	Value
Publication number	US-2016262384-A1
Application number	US-201415034375-A
Country	US
Kind code	A1
Filing date	Nov 5, 2014
Priority date	Nov 5, 2013
Publication date	Sep 15, 2016
Grant date	—

Abstract

The present disclosure provides an antimicrobial composition including a polycationic amphiphile compound, and the method of making and the method of using such a compound or composition. The compound having the formula (I) or (II) R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 10 , or R 11 is H or a C 1-12 alkyl unsubstituted or optionally substituted with a functional group such as —OH, —OR′, —NH 2 , —NHR′, —NR′ 2 , —N—C(0)R′, —N—C(0)CR′═CR′, —SH, —SR′, -0-C(0)R′, —C(0)R′, —CF 3 , —OCF 3 , halogen, benzyl, o-vinylbenzyl, m-vinylbenzyl, p-vinylbenzyl, phenyl, allyl, and substituted allyl. R 7 , R 8 or R 9 is a C 1-12 alkyl unsubstituted or optionally substituted with a functional group such as —OH, —OR′, —NH 2 , —NHR′, —NR′ 2 , —SH, —SR′, -0-C(0)R′, —C(0)R′, —CF 3 , and —OCF 3 . R′ is H or a C 1-4 alkyl. X or Y is a halogen, m and n are integers in the range from 1 to 25.

First claim

What is claimed is:

1 . An antimicrobial composition comprising a compound having the formula

wherein:
R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 10 , or R 11 is H or a C 1-12 alkyl unsubstituted or optionally substituted with a functional group selected from the group consisting of —OH, —OR′, —NH 2 , —NHR′, —NR′ 2 , —N—C(O)R′, —N—C(O)CR′═CR′, —SH, —SR′, —O—C(O)R′, —C(O)R′, —CF 3 , —OCF 3 , halogen, benzyl, o-vinylbenzyl, m-vinylbenzyl, p-vinylbenzyl, phenyl, allyl, and substituted allyl;
R 7 , R 8 or R 9 is a C 1-12 alkyl unsubstituted or optionally substituted with a functional group selected from the group consisting of —OH, —OR′, —NH 2 , —NHR′, —NR′ 2 , —SH, —SR′, —O—C(O)R′, —C(O)R′, —CF 3 , and —OCF 3 ;
R′ is H or a C 1-4 alkyl;
X or Y is a halogen; and
m and n are integers in the range from 1 to 25.

2 . The antimicrobial composition of claim 1 , wherein
R 7 , R 8 or R 9 is a C 2-5 alkyl unsubstituted or optionally substituted.

3 . The antimicrobial composition of claim 1 , wherein
R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 10 , or R 11 is H or a C 1-4 alkyl.

4 . The antimicrobial composition of claim 1 , wherein
at least one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 10 , or R 11 is a C 1-12 alkyl substituted with a functional group selected from the group consisting of —SH, allyl, and substituted allyl.

5 . The antimicrobial composition of claim 1 , wherein
X or Y is chlorine or bromine.

6 . The antimicrobial composition of claim 1 , wherein
m and n are integers in the range from 10 to 16.

7 . The antimicrobial composition of claim 1 , wherein
at least one of m and n is 12.

8 . The antimicrobial composition of claim 1 , wherein the compound has the formula

9 . The antimicrobial composition of claim 8 , wherein in the compound having the formula (I-2) or (I-3), at least one of R 1 and R 2 , and at least one of R 3 and R 4 , and at least one of R 5 and R 6 are methyl.

10 . The antimicrobial composition of claim 8 , wherein in the compound having the formula (I-3), m and n are 12, one of R 3 and R 4 is selected from a group consisting of ethyl, propyl and allyl, and the other groups among R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are methyl.

11 . The antimicrobial composition of claim 1 , wherein the compound has the formula

12 . The antimicrobial composition of claim 11 , wherein in the compound having the formula (II-2) or (II-3), at least one of R 1 and R 2 , and at least one of R 3 and R 4 , at least one of R 5 and R 6 , and at least one of R 10 and R 11 are methyl.

13 . The antimicrobial composition of claim 11 , wherein in the compound having the formula (II-2), m and n are 12, one of R 3 and R 4 is selected from a group consisting of ethyl, propyl and allyl, and the other groups among R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 10 , and R 11 are methyl.

14 . A method of making the antimicrobial composition of claim 1 comprising mixing an effective amount of a compound having the formula (I) or (II) and a carrier.

15 . A method of killing or inhibiting microbial growth, comprising applying the antimicrobial composition of claim 1 comprising a compound having the formula (I) or (II).

16 . The method of claim 15 , wherein the antimicrobial composition is used to kill or inhibit growth of at least one group of microorganisms selected from the group consisting of bacteria, viruses, yeast, fungi, and protozoa, or to inhibit formation of a biofilm or eradicate a pre-established biofilm.

17 . A film or coating comprising a compound

grafted onto a solid surface
wherein:
R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 10 , or R 11 is H or a C 1-12 alkyl unsubstituted or optionally substituted with a functional group selected from the group consisting of —OH, —OR′, —NH 2 , —NHR′, —NR′ 2 , —N—C(O)R′, —N—C(O)CR′═CR′, —SH, —SR′, —O—C(O)R′, —C(O)R′, —CF 3 , —OCF 3 , halogen, benzyl, o-vinylbenzyl, m-vinylbenzyl, p-vinylbenzyl, phenyl, allyl, and substituted allyl;
R 7 , R 8 or R 9 is a C 1-12 alkyl unsubstituted or optionally substituted with a functional group selected from the group consisting of —OH, —OR′, —NH 2 , —NHR′, —NR′ 2 , —SH, —SR′, —O—C(O)R′, —C(O)R′, —CF 3 , and —OCF 3 ;
R′ is H or a C 1-4 alkyl;
X or Y is a halogen; and
m and n are integers in the range from 1 to 25.

18 . The film or coating of claim 17 , wherein the compound grafted on a solid surface has a structure:

wherein L is a linker comprising a functional group.

19 . The film or coating of claim 18 , wherein R4 is a methylene group optionally substituted with a functional group selected from the group consisting of —OH, —OR′, —NH 2 , —NHR′, —NR′ 2 , —SH, —SR′, —O—C(O)R′, —C(O)R′, —CF 3 , and —OCF 3 ;

20 . The film or coating of claim 17 , wherein
R 7 , R 8 or R 9 is a C 2-5 alkyl unsubstituted or optionally substituted.

21 . The film or coating of claim 17 , wherein
R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 10 , or R 11 is H or a C 1-4 alkyl.

22 . The film or coating of claim 17 , wherein
at least one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 10 , or R 11 is a C 1-12 alkyl substituted with a functional group selected from the group consisting of —SH, allyl, and substituted allyl.

23 . The film or coating of claim 17 , wherein
X or Y is chlorine or bromine.

24 . The film or coating of claim 17 , wherein
m and n are integers in the range from 10 to 16.

25 . The film or coating of claim 17 , wherein
at least one of m and n is 12.

Assignees

• Univ Temple
• Univ Villanova

Inventors

• Wuest William
• Minbiole Kevin Patrick

Classifications

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• A61K31/132

  having two or more amino groups, e.g. spermidine, putrescine · CPC title

• A01N25/08

  containing solids as carriers or diluents · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• A01N33/12 Primary

  Quaternary ammonium compounds · CPC title