# US 11,298,561 B2 · Method of treating multi-drug resistance biofilm using targeted laser and antibiotics

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- Number: US 11,298,561 B2
- Document ID: US11298561B2
- Status: Granted
- Kind: B2
- Application number: 16/403,564
- Filed: 2019-05-05
- Published: 2019-08-22
- Granted: 2022-04-12
- Earliest claimed: 2013-05-23
- Assignees: The United States of America as represented by the Secretary of the Navy
- Applicants: The United States of America Represented by the Secretary of Navy
- Inventors: Nancy Millenbaugh
- Web page: https://patentgrep.com/patent/US11298561B2

## CPC

- A61N 5/062: {Photodynamic therapy, i.e. excitation of an agent}
- A61K 41/0052: {Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 47/6835: {the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site}
- A61K 47/6923: {the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb}
- A61N 5/0624: {for eliminating microbes, germs, bacteria on or in the body}
- A61N 5/067: using laser light
- A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B)
- 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)

## Abstract

This application describes a method of using gold nanoparticle (GNP)-targeted pulsed laser technology to enhance antibiotic efficacy against multidrug resistant biofilms. The application also teaches a method for treating topic wound infection using GNP-targeted laser therapy combined with antibiotics treatments.

## Claims

### Claim 1

A method for treating a wound infection, comprising:
a) introducing a composition into a wound, said composition comprising nanoparticles having an electron density that can couple with a photon wave of electromagnetic radiation, wherein said nanoparticles are capable of binding to one or more target microorganisms associated with wound infection;
b) irradiating said wound by said electromagnetic radiation; and
c) administering one or more therapeutic effective dose of an antimicrobial agent to said subject.

### Claim 2 (depends on 1)

The method according to claim 1, wherein said target microorganism is
a) an aerobic and facultative or anaerobic microorganism known to associates with wound infection; or
b) an aerobic or anaerobic isolates from said patient's wound.

### Claim 3 (depends on 2)

The method according to claim 2, wherein the aerobic and facultative or anaerobic microorganism known to associate with wound infection is selected from the group consisting of Streptococcus pyogenes, Staphylococcus aureus/A Methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Enterococci/Vancomycin-resistant Enterococci (VRE), Clostridium dificile, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Stenotrophomonas maltophilia, Burkholderia cepacia, and Ralstonia picketti.

### Claim 4 (depends on 1)

The method according to claim 1, wherein said antimicrobial agent is an antiseptic, or an antibiotics.

### Claim 5 (depends on 4)

The method according to claim 4, wherein said antibiotics is selected from the group consisting of Cephalexin, gentamicin, Augmentin, and amikacin.

### Claim 6 (depends on 4)

The method according to claim 4, wherein said antiseptics is selected from the group consisting of alcohols, quaternary ammonium compounds, chlorhexidine and other diguanides, antibacterial dyes, chlorine and hypochlorites, inorganic iodine compounds, metals, peroxides and permanganates, halogenated phenol derivatives, and quinolone derivatives.

### Claim 7 (depends on 1)

The method according to claim 1, wherein said nanoparticle is metal nanoparticle, a nanoparticle with a core-shell structure, or an electroceramic nanocomposite.

### Claim 8 (depends on 7)

The method according to claim 7, wherein said metal nanoparticle is a gold nanoparticle or a silica nanoparticle coated with a gold shell.

### Claim 9 (depends on 1)

The method according to claim 1, wherein irradiating said wound by said electromagnetic radiation comprises irradiating by a pulsed irradiation source, wherein said pulse of electromagnetic radiation having a pulse length in the range of 10-12 ns at a pulse rate at 1 pulse/second.

### Claim 10 (depends on 1)

The method according to claim 1, wherein said nanoparticles have antibodies, and/or aptamers that binds to said target microorganism.

### Claim 11

A method for eradicating a microbiological film from a surface, the method comprising:
a) introducing a composition into a microbiological film, the composition comprising nanoparticles having an electron density that can couple with a photon wave of electromagnetic radiation wherein said nanoparticles are capable of binding to one or more target microorganisms associated with the microbiological film;
b) irradiating said microbiological film by said electromagnetic radiation such as to generate mechanical force for locally disrupting said microbiological film; and
c) administering to said microbiological film one or more antimicrobial agent.

### Claim 12 (depends on 11)

The method according to claim 11, wherein irradiating said microbiological film by said electromagnetic radiation comprises irradiating the microbiological film by a pulsed irradiation source, said pulse of electromagnetic radiation having a pulse length in the range of 10-12 ns at a pulse rate at 1 pulse/second.

### Claim 13 (depends on 11)

The method according to claim 11, wherein said microbiological film is any group of microorganisms in which cells stick to each other and cells adhere to a surface.

### Claim 14 (depends on 11)

The method according to claim 11, wherein said target microorganism is a bacteria selected from the group consisting of Streptococcus pyogenes, Staphylococcus aureus/Methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Enterococci/Vancomycin-resistant Enterococci (VRE), Clostridium difficile, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Stenotrophomonas maltophilia, Burkholderia cepacia, and Ralstonia picketti.

### Claim 15 (depends on 11)

The method according to claim 11, wherein locally disrupting said microbiological film comprises disrupting the film such that cells become loosened from each other and/or from the surface.

### Claim 16 (depends on 11)

The method according claim 11, said nanoparticle is metal nanoparticle, a nanoparticle with a core-shell structure, or an electroceramic nanocomposite.

### Claim 17 (depends on 16)

The method of claim 16, wherein said metal nanoparticle is a gold nanoparticle or a silica nanoparticle coated with a gold shell.

### Claim 18 (depends on 11)

The method of claim 11, wherein said antimicrobial agent is an antiseptics or an antibiotics.

### Claim 19 (depends on 18)

The method of claim 18, wherein said antibiotics is selected from the group consisting of Cephalexin, gentamicin, Augmentin, and amikacin.

### Claim 20 (depends on 18)

The method of claim 18, wherein said antiseptic is selected from the group consisting of alcohols, quaternary ammonium compounds, chlorhexidine and other diguanides, antibacterial dyes, chlorine and hypochlorites, inorganic iodine compounds, metals, peroxides and permanganates, halogenated phenol derivatives, and quinolone derivatives.

### Claim 21 (depends on 11)

The method according to claim 11, wherein said nanoparticles have antibodies, or aptamer that binds to said target microorganism.

### Claim 22 (depends on 1, 11)

The method according to claims 1 or 11, wherein said composition further comprises an adjuvant or a carrier.

### Claim 23 (depends on 1, 11)

The method according to claim 1 or 11, wherein said antimicrobial agent is administered topically, subcutaneously, intravenously, intramuscularly or orally.
