Utilizing polymers and antibiotics to enhance antimicrobial activity and inhibit antibiotic resistance

Patent metadata

Field	Value
Publication number	US-11766451-B2
Application number	US-202017136709-A
Country	US
Kind code	B2
Filing date	Dec 29, 2020
Priority date	Sep 27, 2018
Publication date	Sep 26, 2023
Grant date	Sep 26, 2023

Abstract

Techniques regarding treating one or more microbe infections with combination therapy are provided. For example, one or more embodiments described herein can comprise a method, which can comprise enhancing an antimicrobial activity of an antibiotic by a combination therapy. The combination therapy can comprise the antibiotic and a polycarbonate polymer functionalized with a guanidinium functional group.

First claim

What is claimed is:

1. A method for treating a bacteria infection, comprising:
contacting the bacteria infection with a combination therapy comprising an antibiotic and a polyionene polymer comprising a terephthalamide structure, wherein the polyionene polymer and the antibiotic in combination provide a synergistic antimicrobial effect comprising an enhancement in an antimicrobial activity of the antibiotic.

2. The method of claim 1 , wherein the polyionene polymer comprises a quaternary ammonium cation.

3. The method of claim 1 , further comprising:
generating, by the polyionene polymer, a hole in a biological membrane of a microbe of the bacteria infection based on the contacting.

4. The method of claim 3 , wherein the microbe is selected from the first group consisting of: Acinetobacter baumannii, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa , and Klebsiella pneumoniae , and wherein the antibiotic is selected from the second group consisting of: rifampicin, tetracycline, azithromycin, ciprofloxacin, ceftazidime, penicillin, gentamicin, imipenem and colistin.

5. The method of claim 4 , wherein the polyionene polymer is characterized by a chemical structure:

wherein “A” is a cation;
wherein “X” is a spacer structure selected from the first group consisting of a first alkyl group and a first aryl group;
wherein “R 3 ” is a hydrophobic functional group selected from the second group consisting of a second alkyl group and a second aryl group; and
wherein “m” is an integer greater than or equal to two and less than or equal to 1000.

6. The method of claim 4 , wherein the polyionene polymer is characterized by a chemical structure:

wherein “m” is an integer greater than or equal to two and less than or equal to 1000.

7. A method for reducing a minimum inhibitory concertation of an antibiotic in association with treating a bacteria infection of a subject, comprising:
administering a combination therapy to the subject, the combination therapy comprising the antibiotic and a polyionene polymer comprising a terephthalamide structure, wherein the polyionene polymer and the antibiotic in combination provide a synergistic antimicrobial effect comprising an enhancement in an antimicrobial activity of the antibiotic.

8. The method of claim 7 , wherein the bacteria infection is caused by a microbe selected from the group consisting of: Acinetobacter baumannii, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa , and Klebsiella pneumoniae.

9. The method of claim 8 , wherein the antibiotic is selected from the group consisting of: rifampicin, tetracycline, azithromycin, ciprofloxacin, ceftazidime, penicillin, gentamicin, imipenem and colistin.

10. The method of claim 7 , wherein the polyionene polymer comprises a quaternary ammonium cation.

11. The method of claim 7 , further comprising:
generating, by the polyionene polymer, a hole in a biological membrane of a microbe of the bacteria infection based on the administering.

12. The method of claim 7 , wherein the polyionene polymer is characterized by a chemical structure:

wherein “A” is a cation;
wherein “X” is a spacer structure selected from the first group consisting of a first alkyl group and a first aryl group;
wherein “R 3 ” is a hydrophobic functional group selected from the second group consisting of a second alkyl group and a second aryl group; and
wherein “m” is an integer greater than or equal to two and less than or equal to 1000.

13. The method of claim 7 , wherein the polyionene polymer is characterized by a chemical structure:

wherein “m” is an integer greater than or equal to two and less than or equal to 1000.

14. A method for inhibiting a development of a resistance to an antibiotic by a bacterium, comprising:
administering, to the bacterium, a mixture of the antibiotic and a polyionene polymer comprising a terephthalamide structure, wherein the polyionene polymer and the antibiotic in combination provide a synergistic antimicrobial effect comprising an enhancement in an antimicrobial activity of the antibiotic.

15. The method of claim 14 , wherein the bacterium is selected from the group consisting of: Acinetobacter baumannii, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa , and Klebsiella pneumoniae.

16. The method of claim 15 , wherein the antibiotic is selected from the group consisting of: rifampicin, tetracycline, azithromycin, ciprofloxacin, ceftazidime, penicillin, gentamicin, imipenem and colistin.

17. The method of claim 14 , wherein the polyionene polymer comprises a quaternary ammonium cation.

18. The method of claim 14 , further comprising:
generating, by the polyionene polymer, a hole in a biological membrane of the bacterium based on the administering.

19. The method of claim 14 , wherein the polyionene polymer is characterized by a chemical structure:

wherein “A” is a cation;
wherein “X” is a spacer structure selected from the first group consisting of a first alkyl group and a first aryl group;
wherein “R 3 ” is a hydrophobic functional group selected from the second group consisting of a second alkyl group and a second aryl group; and
wherein “m” is an integer greater than or equal to two and less than or equal to 1000.

20. The method of claim 14 , wherein the polyionene polymer is characterized by a chemical structure:

wherein “m” is an integer greater than or equal to two and less than or equal to 1000.

Assignees

• IBM
• Agency Science Tech & Res

Inventors

• Hedrick James L
• Bianco Simone
• Kunitomi Mark
• Yang Yi Yan
• Ding Xin
• Yang Chuan
• Liang zhen chang
• De Sessions Paola Florez
• Periaswamy Balamurugan

Classifications

• A61K31/785 Primary

  Polymers containing nitrogen · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• A61K31/407

  condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine · CPC title

• A61K31/43

  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 · CPC title

• A61K31/496

  Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin · CPC title