Lek Pharmaceutical and Chemical Company D.d.

Lek, Tovarna Farmacevtskih in Kemicnih Izdelkov, D.d.

Lek, Tovarna Farmacevtskih

Lek, Tovarna Farmacevtskih in Kemicnih Izdelkov, D.d., Ljubljana

Lek Pharmaceuticals D.d.

Mateja Kovacic

Janko Zmitek

Darja Fercej-Temeljotov

Katarina Verhnjak

Sonja Kotnik

Breda Bole-Vunduk

Breda Husu-Kovacevic

Anton Lavric

Bojan Kofler

A liquid aqueous pharmaceutical suspension formulation containing as amoxycillin trihydrate, potassium clavulanate and microcrystalline cellulose filler is provided.

Pharmaceutical suspension formulation comprising amoxycillin clavulanic acid and cellulose

Inclusion complexes of racemic ibuproxam and of optically active

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.-CD derivative such as heptakis-(2,3,6-tri-O-acetyl)-.beta.-CD in at least equimolar ratio with regard to clavulanic acid. The resulting novel inclusion complexes of clavulanic acid and hydrophobic .beta.-CD 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.-CD derivatives and with hydrophobic .beta.-CD 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.

Inclusion complexes of clavulanic acid and of alkali salts thereof with

Described is a new process for the preparation of alkali clavulanate from an aqueous solution of pure clavulanic acid and of pharmaceutically acceptable potassium 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.-CD derivative such as heptakis-(2,3,6-tri-O-acetyl)-.beta.-CD in equimolar amount or up to 10% excess with regard to clavulanic acid. The resulting novel inclusion complexes of clavulanic acid and hydrophobic .beta.-CD derivative in a molar ratio about 1:1 are isolated, purified with water and then converted with potassium 2-ethyl hexanate to the potassium clavulanate, which is isolated. Furthermore, there are described new inclusion complexes of clavulanic acid and of its pharmaceutically acceptable potassium salt both with hydrophilic .beta.-CD derivatives and with hydrophobic .beta.-CD 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.

Inclusion complexes of clavulanic acid and of potassium salts thereof

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Ljubljana, Slovenia

Mateja Kovacic