Inclusion complexes of clavulanic acid and of alkali salts thereof with hydrophilic and hydrophobic beta-cyclodextrin derivatives, a process for the preparation thereof and the use thereof

Described is a new process for the preparation of alkali clavulanate from an aqueous solution of crude clavulanic acid, which is obtained in a conventional manner after the fermentation with a clavulanic-acid-producing microorganism, extracted with an ethyl acetate solution of a hydrophobic beta -cyclodextrin derivative such as heptakis-(2,3,6-tri-O-acetyl)- beta -cyclodextrin in at least equimolar ratio with regard to clavulanic acid. The resulting novel inclusion complexes of clavulanic acid and hydrophobic beta -cyclodextrin derivative in a molar ratio about 1:1 are isolated, purified and then converted with an alkali base or alkali alkanoate to the desired alkali clavulanate, which is isolated. Furthermore, there are described new inclusion complexes of clavulanic acid and of its pharmaceutically acceptable alkali salts both with hydrophilic beta -cyclodextrin derivatives and with hydrophobic beta -cyclodextrin derivatives, processes for the preparation thereof and the use thereof for the preparation of galenic forms with immediate as well as with sustained action, in combination with amoxicillin trihydrate, which are valuable medicaments in the therapy of infectious diseases.