Laboratori Baldacci S.p.a.

Laboratori Balducci S.p.a.

Universita Di Bologna

Universita' Di Bologna - Dipartimento Di Patologia Sperimentale

Universita' Di Bologna Dipartimento Di Patologia

Luigi Fiume

Alessandro Mattioli

Corrado Busi

Massimo Baldacci

Giuseppina Di Stefano

Guiseppina Di Stefano

Marcella Lanza

Giuseppina D Stefano

A procedure is described for conjugating the hydrazone derivatives of doxorubicin having a maleimide terminal group to lactosaminated human albumin (L-HSA). The procedure is based on the use of trialkyiphosphines to reduce the disulfide bonds of the protein and make its SH groups available for the formation of the thioether bond. In comparison with the conjugation obtained by using thiol reducing agents, such as dithiothreitol, this has the advantage that even when it is performed under very simple conditions, specifically without using an inert atmosphere, in the absence of oxygen, and without preliminary purification of the 'reduced' L-HSA, it does not bring about the formation of a precipitate in the reaction means. In comparison with conjugation to L-HSA thiolated by using iminothiolane, the novel procedure has the advantage of greater simplicity and of not introducing exogenous molecules into the L-HSA in order to make the SH groups available.

Process for the preparation of doxorubicin conjugates with lactosaminated human albumin

The present invention refers to conjugated compounds of antiviral drugs having hepatotropic activity, methods of making these compounds, and compositions thereof.

Hepatotropic conjugates of antiviral drugs carriers thereof and pharmaceutical compositions containing them

Hepatotropic conjugates of antiviral drugs carriers thereof and

Process of conjugation of antiviral nucleosides with lactosaminated

For the preparation of conjugates of adenine-9-beta-D-arabinofuranoside 5'monophosphate (ara-AMP) with lactosaminated human albumin (L-HSA) aqueous solutions of the two components to be conjugated are brought into contact in the presence of 1-ethyl-3-(dimethylaminopropyl)-carbodiimide, by adjusting the pH in the range from slightly acidic to alkaline and by carrying out the conjugate separation. The resulting conjugate, wherein the molar ratio, as determined through spectrophotometric route, between ara-AMP and L-HSA does vary between 5 and 20, remains soluble after lyophilization even at room temperature and shows biological activity at least equivalent to that of the conjugate as prepared according to the known art.

Method for the preparation of conjugates of

A conjugate of 9-(2-hydroxyethoxymethyl)-guanine with lactosaminated human albumin is therapeutically more efficacious than the free drug in the treatment of chronical hepatitis induced from Virus B. For the preparation of the conjugate an aqueous solution of 9-(2-hydroxyethoxymethyl)-guanine in form of a derivative, particularly monophosphate, and an aqueous solution of lactosaminated human albumin are reacted in the presence of 1-ethyl-3-(dimethylaminopropyl)-carbodiimide, by adjusting the pH to the value of 7.5 and by maintaining the reaction mixture for 24 hours under stirring and in the dark.

Conjugate of 9-(2-hydroxyethoxymethyl)-guanine with lactosaminated human

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Bologna, Italy

Luigi Fiume