Means and methods for increasing antibiotic activity

Patent metadata

Field	Value
Publication number	US-2016331708-A1
Application number	US-201515110936-A
Country	US
Kind code	A1
Filing date	Jan 9, 2015
Priority date	Jan 9, 2014
Publication date	Nov 17, 2016
Grant date	—

Abstract

The disclosure provides means and methods for increasing the activity of antibiotics. This enables the use of lower antibiotic dosages and the treatment of multidrug-resistant bacteria.

First claim

1 . A method of treating a subject suffering from or at risk of suffering from a bacterial infection, the method comprising:
administering to the subject an antibiotic and anthranilic acid, or an antibiotic and a pharmaceutically acceptable salt, ester, hydrate, solvate or functional derivative of anthranilic acid, so as to treat the subject suffering from or at risk of suffering from a bacterial infection.

2 . A method for counteracting bacterial activity and/or growth, the method comprising exposing bacteria to:
an antibiotic; and anthranilic acid, or a pharmaceutically acceptable salt, ester, hydrate, solvate or functional derivative thereof.

3 . A method for treating a subject suffering from, or at risk of suffering from, a bacterial infection, the method comprising administering to the subject:
an antibiotic; and anthranilic acid, or a pharmaceutically acceptable salt, ester, hydrate, solvate or functional derivative thereof.

4 . The method according to claim 3 , wherein the subject is a human individual.

5 . The method according to claim 3 , wherein the individual is a child with an age below 18 years or an elderly person with an age above 50 years or an immune-compromised individual.

6 . The method according to claim 3 , comprising:
measuring whether a sample from the subject comprises pathogenic bacteria, proteins from pathogenic bacteria, nucleic acid from pathogenic bacteria, or antibodies against pathogenic bacteria; and administering to the subject an antibiotic and anthranilic acid, or an antibiotic and a pharmaceutically acceptable salt, ester, hydrate, solvate or functional derivative of anthranilic acid, if the sample comprises pathogenic bacteria or proteins from pathogenic bacteria or a nucleic acid molecule from pathogenic bacteria or antibodies against pathogenic bacteria.

7 . A method of increasing the antibacterial activity of an antibiotic, the method comprising:
utilizing anthranilic acid, or a pharmaceutically acceptable salt, ester, hydrate, solvate or functional derivative thereof, for increasing the antibacterial activity of an antibiotic.

8 . The method according to claim 7 , wherein the minimum inhibitory concentration (MIC) of the antibiotic is decreased.

9 . The method according to claim 7 , wherein the antibiotic is used against antibiotic-resistant bacteria.

10 . The method according to claim 7 , wherein an amount of the antibiotic is used that is at most half the amount required for killing bacteria in the absence of anthranilic acid or a pharmaceutically acceptable salt, ester, hydrate, solvate or functional derivative of anthranilic acid.

11 . A composition or kit of parts, comprising:
anthranilic acid, or a pharmaceutically acceptable salt, ester, hydrate, solvate or functional derivative thereof; and an antibiotic in a unit dose that is at most half the amount required for killing bacteria in the absence of anthranilic acid or a pharmaceutically acceptable salt, ester, hydrate, solvate or functional derivative of anthranilic acid.

12 . The kit of parts according to claim 11 , wherein the antibiotic is selected from the group consisting of antibiotics that inhibit bacterial protein synthesis, antibiotics that inhibit cell wall synthesis, antibiotics that disrupt peptidoglycan cross-linkage, antibiotics that inhibit bacterial DNA synthesis and antibiotics that inhibit bacterial RNA synthesis.

13 . The kit of parts of claim 11 , wherein the antibiotic is selected from the group consisting of streptomycin, neomycin, kanamycin, gentamycin, clindamycin, penicillin G, cephalexin, actinomycin and pharmaceutically acceptable salts, esters, hydrates and solvates thereof.

14 . A method for culturing a micro-organism, the method comprising:
culturing the micro-organism in the presence of a plant-derived compound; and determining whether the micro-organism produces a compound with antimicrobial activity and/or a compound that reduces the resistance of bacteria to an antibiotic.

15 . The method according to claim 14 , wherein the plant-derived compound is a plant hormone.

16 . The method according to claim 15 , wherein the plant hormone is a jasmonate.

17 . The method according to claim 16 , wherein the jasmonate is jasmonic acid, methyl jasmonate or jasmone.

18 . The method according to claim 9 , wherein the antibiotic-resistant bacteria is a multidrug-resistant bacteria.

Assignees

• Univ Leiden

Inventors

• Kim Hye Kyong
• Van Der Meij Anne
• Verpoorte Robert
• Choi Young Hae
• Van Wezel Gilles Philippus

Classifications

• A61K31/00

  Medicinal preparations containing organic active ingredients · CPC title

• A61K31/7036

  having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins · CPC title

• A61K38/14

  Peptides containing saccharide radicals; Derivatives thereof {, e.g. bleomycin, phleomycin, muramylpeptides or vancomycin} · CPC title

• A61K31/196 Primary

  the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil · CPC title

• A61K31/545

  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} · CPC title