Metal compositions and methods of use thereof

Inventors: Mingdi Yan (Bedford, MA); William Ndugire (Lowell, MA); Olof Ramstrom (Lowell, MA); N. G. Hasitha Raviranga (Lowell, MA)

Assignee: UNIVERSITY OF MASSACHUSETTS

A61K31/7135 A61K33/242 A61K45/06 A61K47/20 A61P31/04

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Quick Facts

Patent No.: US 12691136
App. No.: 17/997,493
Granted: Jul 28, 2026
Kind: B2

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Abstract

Compositions comprising metal entities in combination with an activating agent, or pharmaceutically acceptable salts thereof are disclosed. Certain compositions are active as antibacterial, antiviral, antifungal, anti-protozoal, and/or anti-worm agents. The disclosure provides pharmaceutical compositions containing the compositions. Methods of using the composition to treat bacterial infections are disclosed.

Claims (28)

1 . A composition comprising: a metal entity and an activating agent, or pharmaceutically acceptable salts thereof, wherein:

the composition comprises a synergistic amount of the activating agent and the metal entity;

the activating agent comprises thiourea; and

the metal entity comprises at least one of auranofin, gold nanoclusters, or a combination thereof, wherein the gold nanoclusters comprise at least one of Au 101 Mal, Au 101 Tre, Au 101 Glc, AuCitrate, Au 18 SG 14 , Au 22 SG 18 , Au 25 SG 18 , Au 101 TPPMS, Au(TPPMS) 2 , [AuTPPMS]Cl, [Au 9 (TPPMS) 8 ]Cl 3 , Au 101 (TPPMS) 21 Cl 5 , HAuCl 4 (Au 3+ ), Au 101 (TPPMS) 19 (Ac 4 Glc) 2 Cl 5 , Au 101 (TPPMS) 14 (Ac 4 Glc) 7 Cl 5 , Au 101 (TPPMS) 11 (Ac 4 Glc) 10 C 15 , Au 101 (TPPMS) 7 (Ac 4 Glc) 14 Cl 5 , or a combination thereof.

2 . The composition of claim 1 , wherein the gold nanoclusters comprise an average diameter of up to 3 nm, the gold nanoclusters comprise an average diameter of greater than 3 nm, or a combination thereof.

3 . The composition of claim 1 , wherein the gold nanoclusters comprise at least one of Au 101 Mal, Au 101 Tre, Au 101 Glc, AuCitrate, Au 18 SG 14 , Au 22 SG 18 , Au 25 SG 18 , Au 101 TPPMS, Au(TPPMS) 2 , [AuTPPMS]Cl, [Au 9 (TPPMS) 8 ]Cl 3 , Au 101 (TPPMS) 21 Cl 5 , HAuCl 4 (Au 3+ ), Au 101 (TPPMS) 19 (Ac 4 Glc) 2 Cl 5 , Au 101 (TPPMS) 14 (Ac 4 Glc) 7 Cl 5 , Au 101 (TPPMS) 11 (Ac 4 Glc) 10 Cl 5 , Au 101 (TPPMS) 7 (Ac 4 Glc) 14 Cl 5 , or a combination thereof.

4 . The composition of claim 1 , wherein the gold nanoclusters comprise at least one of Au 101 Mal, Au 101 Tre, Au 101 Glc, or a combination thereof.

5 . The composition of claim 1 , wherein the gold nanoclusters comprise AuCitrate.

6 . The composition of claim 1 , wherein the metal entity comprises auranofin.

7 . The composition of claim 1 , further comprising a pharmaceutically acceptable carrier.

8 . The composition of claim 1 , wherein the gold nanoclusters comprise at least one of Au 18 SG 14 , Au 22 SG 18 , Au 25 SG 18 , or a combination thereof.

9 . The composition of claim 1 , wherein the gold nanoclusters comprise at least one of [Au 9 (TPPMS) 8 ]Cl 3 , Au 101 (TPPMS) 21 Cl 5 , or a combination thereof.

10 . The composition of claim 1 , wherein the gold nanoclusters comprise at least one of Au 101 (TPPMS) 19 (Ac 4 Glc-S) 2 Cl 5 , Au 101 (TPPMS) 14 (Ac 4 Glc-S) 7 Cl 5 , Au 101 (TPPMS) 11 (Ac 4 Glc-S) 10 Cl 5 , Au 101 (TPPMS) 7 (Ac 4 Glc-S) 14 Cl 5 or a combination thereof.

11 . A composition comprising:

an activating agent that comprises a thiourea; and

a metal compound comprising auranofin or gold nanoclusters, wherein the gold nanoclusters comprise Au 101 Mal, Au 101 Tre, Au 101 Glc, AuCitrate, Au 18 SG 14 , Au 22 SG 18 , Au 25 SG 18 , Au 101 TPPMS, Au(TPPMS) 2 , [AuTPPMS]Cl, [Au 9 (TPPMS) 8 ]Cl 3 , Au 101 (TPPMS) 21 Cl 5 , HAuCl 4 (Au 3+ ), Au 101 (TPPMS) 19 (Ac 4 Glc) 2 Cl 5 , Au 101 (TPPMS) 14 (Ac 4 Glc) 7 Cl 5 , Au 101 (TPPMS) 11 (Ac 4 Glc) 10 Cl 5 , or Au 101 (TPPMS) 7 (Ac 4 Glc) 14 Cl 5 , wherein the composition comprises a synergistic amount of the activating agent and the metal compound.

12 . A method of treating a bacterial infection in a patient comprising administering a therapeutically effective amount of a composition according to claim 1 .

13 . The method of claim 12 , wherein

the bacterial infection is caused by a gram-negative bacterium, a gram-positive bacterium, an ESKAPE pathogen, Escherichia sp., mycobacteria, Pseudomonas sp., Burkholderia sp., Helicobacter sp., Borrelia sp., or a combination thereof;

the method further comprises administering a therapeutically effective amount of an antibacterial agent;

or a combination thereof.

14 . A method of inhibiting the growth of a bacterium in vitro or in vivo comprising contacting a bacterium, virus, parasite, fungus, protozoa, or worm with a composition according to claim 1 .

15 . The method of claim 14 , wherein

the bacterium is a gram-negative bacterium, a gram-positive bacterium, mycobacterium , ESKAPE pathogen, Escherichia sp., Escherichia coli, Pseudomonas sp., Helicobacter sp., Burkholderia sp., Borrelia sp., or a combination thereof;

the method further comprises administering a therapeutically effective amount of an antibacterial agent;

or a combination hereof.

16 . The method of claim 14 , wherein contacting the bacterium with the composition comprises administering a therapeutically effective amount of the composition to a patient with a biofilm infection, wherein the composition is effective at treating the biofilm infection.

17 . The method of claim 14 , wherein contacting the bacterium with the composition comprises contacting a biofilm with the composition in vitro or in vivo, wherein the composition is effective at inhibiting the growth of the biofilm.