# US 11,304,974 B2 · Nanosystems comprising silver and antibiotics and their use for the treatment of bacterial infections

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- Number: US 11,304,974 B2
- Document ID: US11304974B2
- Status: Granted
- Kind: B2
- Application number: 16/489,207
- Filed: 2018-04-09
- Published: 2020-10-22
- Granted: 2022-04-19
- Earliest claimed: 2017-04-10
- Assignees: Laboratorios Enosan, S.L.
- Applicants: Luis Jesús Lostao Camón
- Inventors: Luis Jesús Lostao Camón
- Web page: https://patentgrep.com/patent/US11304974B2

## CPC

- A61K 9/501: {Inorganic compounds}
- A61K 33/38: Silver; Compounds thereof
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 9/08: Solutions {(composition of solutions A61K47/00)}
- A61K 9/14: Particulate form, e.g. powders, {Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles (microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51)}
- A61K 9/1611: {Inorganic compounds}
- A61K 9/1676: {having a drug-free core with discrete complete coating layer containing drug (adsorbates of liquid drug formulations on inert powders without simultaneous granulation step A61K9/141; with further drug-free outer coating A61K9/5078; drug conjugated to non-active particles A61K47/6921)}
- A61K 31/165: having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K 31/351: not condensed with another ring
- A61K 31/4178: not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
- A61K 31/43: Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula [IMAGE cpc-sch-A61K-0952.gif], e.g. penicillins, penems
- A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
- A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol
- A61K 31/545: Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula: [IMAGE cpc-sch-A61K-0953.gif] , e.g. cephalosporins, {cefaclor, or cephalexine}
- A61K 31/575: substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
- A61K 31/65: Tetracyclines
- A61K 31/665: having oxygen as a ring hetero atom, e.g. fosfomycin
- A61K 31/7056: containing five-membered rings with nitrogen as a ring hetero atom
- A61K 38/12: Cyclic peptides {, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C (A61K38/043 - A61K38/046 take precedence)}
- A61K 38/14: Peptides containing saccharide radicals; Derivatives thereof {, e.g. bleomycin, phleomycin, muramylpeptides or vancomycin}
- A61K 47/02: Inorganic compounds
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- 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)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

A composition including metallic silver nanoparticles is supported on a carrier, wherein the carrier is in the form of particles. The carrier is selected from an inert carrier or an antibiotic. The composition further includes at least one antibiotic in the case the carrier is an inert carrier. A related nanosystem includes a composition having metallic silver nanoparticles or a mixture of silver nanoparticles and at least one antibiotic for use in the treatment of an infection caused by at least one strain of bacteria resistant to at least one antibiotic. Pharmaceutical compositions and methods for the preparation of these compositions and nanosystems are also used for the treatment of bacterial infections.

## Claims

### Claim 1

A composition, comprising metallic silver nanoparticles supported on a carrier, the carrier being in the form of particles, wherein the carrier is an antibiotic.

### Claim 2 (depends on 1)

The composition according to claim 1, the particles having a mean diameter between 0.1 and 200 micrometers.

### Claim 3 (depends on 1)

The composition according to claim 1, wherein the antibiotic is selected from penicillins, cephalosporins, monobactams, beta lactamase inhibitors, carbapenems, aminoglucosides, quinolones, tetracyclines, glicopeptides, colistin, sulfamethoxazole/trimethoprim, fosfomycin, nitrofurantoin, chloramphenicol, clindamycin, fusidic acid, linezolid, mupirocin, daptomycin, clindamycin and rifampicin.

### Claim 4 (depends on 1)

The composition according to claim 1, wherein the weight ratio of silver with respect to the total amount of antibiotics is between 10:100 and 0.1:100.

### Claim 5 (depends on 1)

The composition according to claim 1, wherein the mean particle size of the metallic silver nanoparticles is comprised between 1 and 100 nanometers.

### Claim 6 (depends on 1)

A nanosystem comprising a composition according to claim 1 or a mixture of silver nanoparticles and at least one antibiotic, for use in the treatment of an infection caused by at least one strain of bacteria resistant to at least one antibiotic.

### Claim 7 (depends on 6)

The nanosystem according to claim 6, wherein the infection is caused by at least one strain of gram negative bacteria, resistant to at least one antibiotic.

### Claim 8 (depends on 6)

The nanosystem according to claim 6, which comprises a mixture of silver nanoparticles and an antibiotic, wherein the antibiotic is selected from penicillins, cephalosporins, monobactams, beta lactamase inhibitors, carbapenems, aminoglucosides, quinolones, tetracyclines, glicopeptides, colistin, sulfamethoxazole/trimethoprim, fosfomycin, nitrofurantoin, chloramphenicol, clindamycin, fusidic acid, linezolid, mupirocin, daptomycin, clindamycin and rifampicin.

### Claim 9 (depends on 8)

The nanosystem according to claim 8, comprising colloidal silver nanoparticles and at least one antibiotic, for use in the treatment of an infection caused by at least one strain of bacteria resistant to at least one antibiotic.

### Claim 10 (depends on 8)

The nanosystem according to claim 8, wherein the silver nanoparticles are used in a weight ratio with respect to the total amount of antibiotics between 1:100 and 0.1:100.

### Claim 11 (depends on 1)

A preparation process of a composition according to claim 1, the process including the following steps:
a) preparing a dissolution of a silver ion;
b) adding said silver ion dissolution to a carrier in the form of particles, wherein the carrier is an antibiotic; and
c) adding a reducing agent to the mixture obtained in b), to obtain metallic silver supported on said carrier.

### Claim 12 (depends on 1)

A pharmaceutical composition which comprises at least one pharmaceutically acceptable excipient and a composition according to claim 1, for use as a medicament.

### Claim 13 (depends on 1)

A pharmaceutical composition which comprises at least one pharmaceutically acceptable excipient and a composition according to claim 1, for use in the treatment of an infection.

### Claim 14 (depends on 1)

A pharmaceutical composition which comprises at least one pharmaceutically acceptable excipient and a composition according to claim 1, for oral use in the treatment of an infection.

### Claim 15 (depends on 1)

The composition according to claim 1, wherein the mean particle size of the metallic silver nanoparticles is comprised between 10 and 90 nanometers.

### Claim 16 (depends on 1)

The composition according to claim 1, wherein the mean particle size of the metallic silver nanoparticles is comprised between 10 and 70 nanometers.

### Claim 17 (depends on 1)

The composition according to claim 1, wherein the mean particle size of the metallic silver nanoparticles is comprised between 10 and 50 nanometers.

### Claim 18 (depends on 1)

The composition according to claim 1, wherein the mean particle size of the metallic silver nanoparticles is comprised between 20 and 30 nanometers.