Composition comprising selenazol or thiazolone derivatives and silver and method of treatment therewith

• US 10,058,542 B1
• Filed: 09/10/2015
• Issued: 08/28/2018
• Est. Priority Date: 09/12/2014
• Status: Active Grant

• Current Assignee: Thioredoxin System AB
• Original Assignee: Thioredoxin System AB
• Inventors: Holmgren, Arne, Lu, Jun
• Primary Examiner(s): Pipic, Alma
• Application Number:
  US14/850,567
• Time in Patent Office: 1,083 Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/41 having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
• CPC Class Codes: A61K 31/437 the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 31/444 containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
• CPC Class Codes: A61K 33/38 Silver; Compounds thereof
• CPC Class Codes: C12Q 1/18 Testing for antimicrobial activity of a material
• CPC Class Codes: 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

Abstract

A method for treating a prokaryotic infection in an animal or human by administering a pharmaceutically acceptable composition, comprising administering a source of silver ions and a benzoisoselenazol derivative, e.g., an ebselen derivative.

Claims

1. A composition for treating a prokaryotic infection in an animal or human, comprising a unit dosage form adapted for administration enterally or by application to skin or mucous membranes, of:

at least one compound according to Formula I or a pharmaceutically acceptable salt thereof, in an amount of at least 25 mg;

2. The composition according to claim 1, wherein the at least one compound according to Formula I or a pharmaceutically acceptable salt thereof is present in a therapeutically amount of between 25 mg and 1000 mg, and the effective amount of the source of the at least one metal ion comprises a dissolvable silver salt present in a therapeutically effective amount to provide between 20 mg and 100 mg of silver ions.

3. The composition according to claim 1, wherein X is selenium.

4. The composition according to claim 1, wherein Formula I is ebselen.

5. The composition according to claim 1, wherein Formula I is ebsulfur-23.

12. The composition according to claim 1, wherein the at least one compound according to Formula I is a benzoisoselenazol or a pharmaceutically acceptable salt thereof.

13. The composition according to claim 1, wherein the at least one compound according to Formula I is a benzoisothiazol or a pharmaceutically acceptable salt thereof.

14. The composition according to claim 1, wherein the effective amount of the source of the at least at least one metal ion comprises a silver salt or a silver complex of the at least one compound according to Formula I.

16. The composition according to claim 1, wherein the source of the at least one metal ion comprises at least one of silver ions;

a silver colloid, and an organo-silver complex.

17. The composition according to claim 1, wherein the source of the at least one metal ion is provided by an insoluble source of metal ions which release the metal ions for an extended duration at a constant rate.

6. A composition for treating a prokaryotic infection in an animal or human, comprising a pharmaceutically acceptable unit dosage form comprising:

an effective amount of at least one compound according to Formula I or a pharmaceutically acceptable salt thereof to treat the prokaryotic infection;

7. The composition according to claim 6, wherein the compound according to Formula I or a pharmaceutically acceptable salt thereof is present in a therapeutically effective amount of between 25 mg and 1000 mg, and the source of the at least one metal ion comprises a source of silver ions present in a therapeutically effective amount to provide between 20 mg and 100 mg of silver ions.

8. The composition according to claim 6, wherein X is selenium.

9. The composition according to claim 6, wherein Formula I is ebselen or a pharmaceutically acceptable salt thereof.

10. The composition according to claim 6, wherein Formula I is ebsulfur-23 or a pharmaceutically acceptable salt thereof.

11. The composition according to claim 6:

wherein X is selenium or sulfur,

wherein R is selected from the group consisting of;

aryl or heteroaryl which is optionally substituted with C₁-C₅ alkyl, OH, alkoxyl, SH, NH₂, N-alkylamino, N,N-dialkylamino, COOH, CHO, NO₂, F, Cl, Br, and I,

wherein A represents a polyunsaturated 6 member carbon chain.

15. The composition according to claim 6, wherein the at least one compound according to Formula I is a benzoisothiazol or a pharmaceutically acceptable salt thereof and comprises ebsulfur-23.

18. A method of treating a prokaryotic infection in an animal or human having a systemic infection with the prokaryotic organism, comprising:

obtaining a microbiological sample from a patient comprising the prokaryotic organism; and

determining a sensitivity of the prokaryotic organism to a range of pharmaceutically acceptable treatments with at least one composition of claim 6, wherein the range of pharmaceutically acceptable treatments comprise systemic administration of at least one compound according to Formula I and the at least one metal ion in a respective amount to produce a synergistic inhibition of a prokaryotic thioredoxin reductase of the prokaryotic organism; and

treating the patient with a pharmaceutically acceptable treatment with the at least one compound according to Formula I, and the source of the at least one metal ion in a respective amount to produce a synergistic inhibition of a prokaryotic thioredoxin reductase of the prokaryotic organism, which achieves inhibition of growth of the prokaryotic organism in the animal or human, based on the determined sensitivity.

19. The composition according to claim 6, wherein the at least one compound according to Formula I or a pharmaceutically acceptable salt thereof comprises ebselen and the source of the at least one metal ion comprises silver nitrate.