Potassium clavulanate

Description

Clavulanate is a β-lactamase inhibitor that is effective against Ambler class A β-lactamases (IC₅₀ values range from 12 to 60 nM). While it is not an effective antibiotic by itself, clavulanate is commonly used with other antibiotics that would be inactivated by β-lactamases secreted by bacteria. It is often combined with amoxicillin and other penicillin-based antibiotics.

Chemical properties

Pale Yellowish Solid

Originator

Clavulanate ,potassium Lek

The Uses of Potassium clavulanate

A -Lactamase inhibitor, typically added to amoxicillin to increase its effectiveness

The Uses of Potassium clavulanate

Clavulanic Acid is a β-lactamase inhibitor, typically added to amoxicillin to increase its effectiveness.

The Uses of Potassium clavulanate

Clavulanic acid is a β-lactam antibiotic produced by several species of Streptomyces. The free acid degrades and is isolated and maintained as either the sodium or potassium salt. Clavulanate is a weak antibiotic, but is a potent inhibitor of β-lactamases. In combination with penicillin and cephalosporins, it shows potent synergistic activity. Clavulanic acid is a suicide inhibitor, covalently binding to a serine residue in the active site of the β-lactamase.

What are the applications of Application

Clavulanic acid potassium salt is a β-Lactamase inhibitor effective against Ambler class A β-lactamases.

Definition

ChEBI: A potassium salt having clavulanate as the counterion. It acts as a suicide inhibitor of bacterial beta-lactamase enzymes and has only weak anitbiotic activity when administered alone. However it can be used in combination with amoxicillin trihydrate (under the trade name Augmentin) for treatment of a variety of bacterial infections, where it prevents antibiotic inactivation by microbial lactamases.

Manufacturing Process

Clavulanic acid may be obtained by aerobic cultivation of Streptomyces clavuligerus in conventional nutrient media at, for example, about 25°-30°C under roughly neutral conditions.
Cultivation of Streptomyces clavuligeru: Streptomyces clavuligerus was cultivated at 26°C on agar slopes containing 1% Yeatex (yeast extract) ("Yeatex" is a Registered Trade mark), 1% glucose and 2% Oxoid agar No. 3, pH 6.8. A sterile loop was used to transfer mycelium and spores from the slope into 100 ml of a liquid medium in a 500 ml Ehrlenmeyer flask. The liquid medium had the following composition: Oxoid Malt Extract 10g/L, Oxoid Bacteriological Peptone 10g/L, Glycerol 20 g/L, Tap water 1 L.
The medium was adjusted to pH 7.0 with sodium hydroxide solution and 100 ml volumes dispensed into flasks which were closed with foam plugs prior to autoclaving at 15 lb/sq.in. for 20 min. An inoculated seed flask was shaken for 3 days at 26°C on a rotary shaker with a 2 inch throw and a speed of 240 r.p.m.
Production stage flasks containing the liquid medium described above were inoculated with 5% vegetative inoculum and grown under the same conditions as the seed flask.
Clavulanic acid may be extracted from the culture medium. Normally the cells of the Streptomyces clavuligerus are first removed from culture medium by filtration or centrifugation. Then clavulanic acid is extracted into an organic solvent, for example, n-butanol or ethyl acetate, or n-butyl acetate, or methyl isobutyl ketone. Then n-butanol fraction are treated with new aqueous phase using potassium hydrogen carbonate and then this aqueous phase is washed with n-butanol. This aqueous extract, after separation of the phases, is concentrated under reduced pressure. Freeze-drying at -20°C may also be
employed to provide a solid crude preparation of the potassium Z-(2R,5R)-3- (β-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3,2,0]heptane-2-carboxylate (clavulanate potassium).

Therapeutic Function

Beta-lactamase inhibitor