# US 10,440,955 B2 · Methods comprising a biocidal polyamine

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- Number: US 10,440,955 B2
- Document ID: US10440955B2
- Status: Granted
- Kind: B2
- Application number: 15/806,701
- Filed: 2017-11-08
- Published: 2018-05-10
- Granted: 2019-10-15
- Earliest claimed: 2013-05-22
- Assignees: Curza Global, LLC; University of Utah Research Foundation
- Applicants: Curza Global, LLC; University of Utah Research Foundation
- Inventors: Ryan Looper; Dustin Williams; Sujeevini Jeyapalina; Travis Haussener; Paul R. Sebahar; Hariprasada R. Kanna Reddy
- Web page: https://patentgrep.com/patent/US10440955B2

## CPC

- A01N 47/28: Ureas or thioureas containing the groups >N—CO—N< or >N—CS—N< (isoureas, isothioureas A01N47/42)
- A01N 33/04: Nitrogen directly attached to aliphatic or cycloaliphatic carbon atoms
- A01N 33/08: containing oxygen or sulfur
- A01N 33/10: having at least one oxygen or sulfur atom directly attached to an aromatic ring system
- A01N 37/18: containing the group —CO—N<, e.g. carboxylic acid amides or imides; Thio analogues thereof
- A01N 37/30: containing the groups —CO—N< and [IMAGE cpc-sch-A01N-0938.gif], both being directly attached by their carbon atoms to the same carbon skeleton, e.g. H2N—NH—CO—C6H4—COOCH3; Thio-analogues thereof
- A01N 37/40: having at least one carboxylic group or a thio analogue, or a derivative thereof, and one oxygen or sulfur atom attached to the same aromatic ring system
- A01N 43/10: with sulfur as the ring hetero atom
- A01N 43/30: with two oxygen atoms in positions 1,3, condensed with a carbocyclic ring
- A01N 43/40: six-membered rings
- A01N 43/54: 1,3-Diazines; Hydrogenated 1,3-diazines
- A01N 43/56: 1,2-Diazoles; Hydrogenated 1,2-diazoles
- A01N 43/84: six-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,4
- A01N 47/12: containing a —O—CO—N< group, or a thio analogue thereof, neither directly attached to a ring nor the nitrogen atom being a member of a heterocyclic ring
- A61K 8/41: Amines
- A61K 8/42: Amides
- A61K 8/49: containing heterocyclic compounds
- A61K 8/4926: {having six membered rings}
- A61K 8/494: {with more than one nitrogen as the only hetero atom}
- A61K 8/4953: {containing pyrimidine ring derivatives, e.g. minoxidil}
- A61K 8/4973: {with oxygen as the only hetero atom}
- A61K 8/4986: {with sulfur as the only hetero atom}
- A61K 31/135: having aromatic rings {, e.g. ketamine, nortriptyline (methadone A61K31/137)}
- A61K 31/166: having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
- A61L 2/232: layered or coated
- A61L 29/14: Materials characterised by their function or physical properties {, e.g. lubricating compositions}
- A61L 31/14: Materials characterised by their function or physical properties {, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials}
- A61Q 5/02: Preparations for cleaning the hair
- A61Q 15/00: Anti-perspirants or body deodorants (deodorisation of air A61L9/00)
- A61Q 19/007: {Preparations for dry skin}
- A61Q 19/10: Washing or bathing preparations
- C07C 211/27: having amino groups linked to the six-membered aromatic ring by saturated carbon chains
- C07C 211/29: the carbon skeleton being further substituted by halogen atoms or by nitro or nitroso groups
- C07C 217/58: with amino groups and the six-membered aromatic ring, or the condensed ring system containing that ring, bound to the same carbon atom of the carbon chain
- C07C 233/78: with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
- C07C 271/20: to carbon atoms of hydrocarbon radicals substituted by nitrogen atoms not being part of nitro or nitroso groups
- C07C 275/14: being further substituted by nitrogen atoms not being part of nitro or nitroso groups
- C07D 295/135: with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
- C07D 317/58: Radicals substituted by nitrogen atoms (nitro radicals C07D317/52)
- C09D 5/14: Paints containing biocides, e.g. fungicides, insecticides or pesticides (C09D5/16 takes precedence)
- A61L 2/18: Liquid substances
- A61L 2/22: Phase substances, e.g. smokes or aerosols
- A61L 2/235: cellular, porous or foamed
- A61L 12/14: Organic compounds not covered by groups A61L12/10 or A61L12/12
- A61L 2103/05: Living organisms or biological materials
- A61L 2103/06: The human body
- A61L 2103/15: Laboratory, medical or dentistry appliances, e.g. catheters or sharps
- C07C 2601/14: The ring being saturated
- C08K 5/17: Amines; Quaternary ammonium compounds
- A01N: PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF (preservation of food or foodstuff A23); BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES (preparations for medical, dental or toiletry purposes which kill or prevent the growth or proliferation of unwanted organisms A61K); PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K)
- A61Q: SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- C09D: COATING COMPOSITIONS, e.g. PAINTS, VARNISHES OR LACQUERS; FILLING PASTES; CHEMICAL PAINT OR INK REMOVERS; INKS; CORRECTING FLUIDS; WOODSTAINS; PASTES OR SOLIDS FOR COLOURING OR PRINTING; USE OF MATERIALS THEREFOR (cosmetics A61K; processes for applying liquids or other fluent materials to surfaces, in general, B05D; staining wood B27K5/02; glazes or vitreous enamels C03C; natural resins, French polish, drying-oils, driers, turpentine, per se, C09F; polishing compositions other than French polish, ski waxes C09G; adhesives or use of materials as adhesives C09J; materials for sealing or packing joints or covers C09K3/10; materials for stopping leaks C09K3/12; processes for the electrolytic or electrophoretic production of coatings C25D)
- C08K: Use of inorganic or non-macromolecular organic substances as compounding ingredients (paints, inks, varnishes, dyes, polishes, adhesives C09)

## Abstract

Compounds, compositions, and methods comprising a polyamine compound are described, which may be used to kill, disperse, treat, or reduce biofilms, or to 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.

## Claims

### Claim 1

A method for dispersing or killing a biofilm on a subject, the method comprising a step of topically, orally, transmucosally, vaginally, or rectally administering an anti-biofilm composition to a surface of the subject, thereby effectively dispersing or killing the biofilm;
wherein the anti-biofilm composition comprises
(i) a pharmaceutically acceptable carrier; and
(ii) a therapeutically effective amount of a biocidal polyamine compound;
wherein the biocidal polyamine compound is selected from the group consisting of:
and a salt thereof;
wherein:
each Ra is independently a group of Formula II:
each of the An members is independently selected from the group consisting of CRa and CR5; or, alternatively, a pair of adjacent An members join to form a cycloalkyl, aryl, heterocyclyl, or heterocycloaryl ring; wherein at least one An member and at most three An members are independently selected CRa,
each R1a and R1b is a member independently selected from the group consisting of hydrogen, fluoro, alkyl, and fluoroalkyl;
each R2a, R2b, R2c, and R2d is a member independently selected from the group consisting of hydrogen, alkyl, fluoroalkyl, alkenyl, alkynyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl; alternatively, a pair of R2n members from the Ra group independently selected from the group R2a and R2b, and R2c and R2d join to form a ring independently selected from the group consisting of spirocycloalkyl and spiroheterocycyl; or, alternatively, the R2a and the R2c from the Ra group join to form a ring independently selected from the group consisting of cycloalkyl and heterocycyl;
each Rm is a member independently selected from the group consisting of —CR2aR2b—, —CR2cR2d—, —C(R2a)=(R2b)—, —CC— and —C(R2a)(R2b)-L2-C(R2c)(R2d)—;
m is 1;
each L1 and L2 is a member independently selected from the group consisting of a bond, —O—, —C(O)O—, —NR4—, —NR4C(O)—, and C(O)NR4—;
each R3 is a member independently selected from the group consisting of —Z1—Y1—R4 and —Z1—Y1—Y2—R4;
each R4 is a member independently selected from the group consisting of hydrogen, alkyl, fluoroalkyl, alkenyl, alkynyl, aryl, heteroaryl, arylalkyl, and heteroarylalkyl; or, alternatively, for a —N(R4)2 group, one of the two R4 in the group is a member selected from the group consisting of —(CO)OR6a—, (CO)N(R6a)(R6b), and —C(NR6a)N(R6b)(R6c);
each R5 is a member independently selected from the group consisting of hydrogen, alkyl, hydroxyl, alkoxy, alkylamino, alkenyl, alkynyl, aryl, aryloxy, arylamino, cycloalkyl, cycloalkoxy, cycloalkylamino, heterocyclyl, heterocycyloxy, heterocycylamino, halo, haloalkyl, fluoroalkyloxy, heteroaryl, heteroaryloxy, heteroarylamino, arylalkyl, arylalkyloxy, arylalkylamino, heteroarylalkyl, heteroarylalkyloxy, heteroarylalkylamino; hydroxyalkyl, aminoalkyl, and alkylaminoalkyl;
each Y1 and Y2 is an independently selected group of Formula IA:
each Z1 and Z2 is an independently selected NR4; and
each R6a, R6b, and R6c is a member independently selected from the group consisting of hydrogen, alkyl, fluoroalkyl, alkenyl, alkynyl, aryl, heteroaryl, arylalkyl, cycloalkyl, and heteroarylalkyl; or, alternatively, two R6n members R6a and R6b or R6a and R6c form a heterocycyl ring;
wherein the biocidal polyamine compound comprises at least two primary or secondary amino groups.

### Claim 2 (depends on 1)

The method of claim 1, wherein:
each R2a, R2b, R2c, and R2d is a member independently selected from the group consisting of hydrogen, alkyl, fluoroalkyl, alkenyl, alkynyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl.

### Claim 3 (depends on 2)

The method of claim 2, wherein:
each R1a and R1b is a member independently selected from the group consisting of hydrogen and alkyl.

### Claim 4 (depends on 1)

The method of claim 1, wherein the biocidal polyamine compound comprises at least four primary or secondary amino groups.

### Claim 5 (depends on 1)

The method of claim 1, wherein the biocidal polyamine compound is selected from the group consisting of
and a salt thereof;
wherein each An member is an independently selected CR5.

### Claim 6 (depends on 5)

The method of claim 5, wherein the biocidal polyamine compound is selected from the group consisting of
and a salt thereof; and
wherein Ra is an independently selected group of Formula VII:

### Claim 7 (depends on 5)

The method of claim 5, wherein Ra is —CH2[NH(CH2)n]pNH2;
wherein each n is an integer independently selected from 3 to 12; and
wherein each p is an integer independently selected from 1 to 3.

### Claim 8 (depends on 5)

The method of claim 5, wherein the biocidal polyamine compound is selected from the group consisting of
and a salt thereof.

### Claim 9 (depends on 1)

The method of claim 1, wherein the anti-biofilm composition is a liquid, a gel, a paste, or a powder.

### Claim 10 (depends on 1)

The method of claim 1, wherein the biofilm comprises an antibiotic-resistant bacterial species.

### Claim 11 (depends on 1)

The method of claim 1, wherein the anti-biofilm composition is an aerosol spray, a solution, a suspension, a gel, a paste, a cream, or a foam.

### Claim 12 (depends on 11)

The method of claim 11, wherein the anti-biofilm composition is the cream.

### Claim 13 (depends on 1)

The method of claim 1, wherein the anti-biofilm composition is a tablet, a pill, a troche, or a capsule.

### Claim 14 (depends on 1)

The method of claim 1, the surface is a dermal surface, a mucosal surface, an oral surface, a urinary tract surface, a vaginal tract surface, or a lung surface.

### Claim 15 (depends on 1)

The method of claim 1, wherein the surface is skin or soft tissue that has been compromised by dermatitis, ulcers, a burn injury, or trauma.

### Claim 16 (depends on 1)

The method of claim 1, wherein the method comprises a step of treating a patient with a biofilm-related disorder.

### Claim 17 (depends on 16)

The method of claim 16, wherein the biofilm-related disorder is an infection, pneumonia, cystic fibrosis, otitis media, a urinary tract disorder, a periodontal disease, bronchiectasis, dental caries, or acne.