Methods of use comprising a biocidal polyamine
Compounds, compositions, and methods comprising a polyamine compound are described, which may be used to kill, disperse, treat, reduce biofilms, and/or inhibit or substantially prevent biofilm formation. In certain aspects, the present invention relates to compounds, compositions, and methods comprising polyamine compounds that have antimicrobial or dispersing activity against a variety of bacterial strains capable of forming biofilms.
1. A method for dispersing or killing a biofilm, the method comprising a step of contacting the biofilm with an anti-biofilm composition, thereby dispersing or killing the biofilm;
wherein the anti-biofilm composition comprises a biocidal polyamine compound selected from the group consisting of:
and a salt thereof;
wherein:
each R a is an independently selected group of the formula:
each R m is a member independently selected from the group consisting of —CR 2a R 2b —, —C(R 2a )═(R 2b )—, —CC—, and —C(R 2a )(R 2b )-L-C(R 2c )(R 2d )—;
each m is an integer independently selected from 1 to 10;
each R 2a , R 2b , R 2c , and R 2d is a member independently selected from the group consisting of hydrogen, alkyl, fluoroalkyl, alkenyl, alkynyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl; alternatively, a pair of R 2 members from the same R a group independently selected from the group consisting of the pair R 2a and R 2b and the pair R 2c and R 2d join to form a member independently selected from the group consisting of spirocycloalkyl, spiroheterocycyl, and oxo; or, alternatively, an R 2a and an R 2c from the same R a group join to form a ring independently selected from the group consisting of cycloalkyl and heterocycyl;
each L is a member independently selected from the group consisting of a bond, —O—, —C(O)O—, —NR 4 —, —NR 4 C(O)—, and —C(O)NR 4 —;
each R 3 is a member independently selected from the group consisting of —Z 1 —Y 1 —R 4 and —Z—Y 1 —Y 2 —R 4 ;
each R 4 is a member independently selected from the group consisting of hydrogen, alkyl, fluoroalkyl, alkenyl, alkynyl, arylalkyl, and heteroarylalkyl; or, alternatively, for a —N(R 4 ) 2 group, one of the two R 4 in the group is a member selected from the group consisting of —(CO)OR 6a —, (CO)N(R 6a )(R 6b ), and —C(NR 6a )N(R 6b )(R 6c );
each Y 1 and Y 2 is an independently selected group of the formula:
each Z 1 and Z 2 is an independently selected NR 4 ; and
each R 6a , R 6b , and R 6c is a member independently selected from the group consisting of hydrogen, alkyl, and fluoroalkyl; or, alternatively, two R 6 members R 6a and R 6b or R 6a and R 6c join to form an additional heterocycyl ring;
wherein the biocidal polyamine compound comprises at least four primary or secondary amino groups.
2. The method of claim 1 , wherein the biocidal polyamine compound comprises at least six primary or secondary amino groups.
3. The method of claim 1 , wherein the biocidal polyamine compound is selected from the group consisting of:
and a salt thereof.
4. The method of claim 3 , wherein m is 1 or 2; and wherein R m is —CH 2 —.
5. The method of claim 4 , wherein the biocidal polyamine salt is a hydrochloride.
6. The method of claim 4 , wherein R 4 is selected from the group consisting of hydrogen and alkyl.
7. The method of claim 6 , wherein R 4 is isobutyl.
8. The method of claim 4 , wherein the biocidal polyamine compound is selected from the group consisting of
and a salt thereof.
9. The method of claim 1 , wherein the biocidal polyamine compound is selected from the group consisting of:
and a salt thereof.
10. The method of claim 9 , wherein m is 1 or 2; and wherein R m is —CH 2 —.
11. The method of claim 10 , wherein the biocidal polyamine salt is a hydrochloride.
12. The method of claim 10 , wherein R 4 is selected from the group consisting of hydrogen and alkyl.
13. The method of claim 12 , wherein R 4 is isobutyl.
14. The method of claim 10 , wherein the biocidal polyamine compound is selected from the group consisting of
and a salt thereof.
15. The method of claim 1 , wherein the step of treating the biofilm with an anti-biofilm composition disperses the biofilm.
16. The method of claim 1 , wherein the biofilm comprises an antibiotic-resistant bacterial species.
17. The method of claim 1 , wherein the method comprises a step of treating a contact lens with the anti-biofilm composition.
18. The method of claim 1 , wherein the method comprises a step of treating a pipe with the anti-biofilm composition.
19. The method of claim 1 , wherein the method comprises a step of treating a heating or cooling tower with the anti-biofilm composition.
20. The method of claim 1 , wherein the method comprises a step of coating an object with the anti-biofilm composition.
21. The method of claim 1 , wherein the anti-biofilm composition is a paint.
22. The method of claim 1 , wherein the method comprises a step of treating a patient with a biofilm-related disorder.
23. A method for inhibiting formation of a biofilm, the method comprising a step of treating planktonic bacteria with an anti-biofilm composition of claim 1 , thereby inhibiting incorporation of the planktonic bacteria into the biofilm.