Abstract: 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.

Abstract: The present invention refers to the use of a conjugate of doxorubicin with lactosaminated human albumin for the preparation of a pharmaceutical composition useful in the treatment of hepatocellular carcinomas (HCCs) which do not express the asialoglycoprotein receptor (ASGP-R). The conjugate which was previously prepared and studied only for the treatment of HCCs expressing the ASGP-R, has now been shown to possess the potentiality of a beneficial use also in the treatment of the HCCs which do not have the receptor. Therefore, compositions containing the conjugate could be administered for treatment of all HCCs, without the need of a preliminary tumor biopsy to demonstrate the presence or the absence of the receptor.

Abstract: A procedure is described for conjugating the hydrazone derivatives of doxorubicin having a maleimide terminal group to lactosaminated human albumin (L-HAS). The procedure is based on the use of trialkylphosphines 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-HAS, it does not bring about the formation of a precipitate in the reaction means. In comparison with conjugation to L-HAS thiolated by using iminothiolane, the novel procedure has the advantage of greater simplicity and of not introducing exogenous molecules into the L-HAS in order to make the SH groups available.

Abstract: Pharmaceutical compositions containing as active compound conjugates of lactosaminated albumin with antiblastic nucleosides (and their analogs) are here described. These compositions are particularly useful to increase the efficacy of the antiblastic nucleosides (and their analogs) on liver micrometastases. They preferably consist of aqueous solutions administered by parenteral route, preferably by intravenous injection. The antiblastic nucleoside of choice is 5-fluoro-2′-deoxyuridine (FUdR).

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

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

Abstract: A conjugate of an antiviral nucleoside with a lactosaminated human albumin (L-HSA) and its method of preparation is described. The method of preparation involves the reaction of an antiviral phosphorylated nucleoside in the form of an imidizolide with L-HSA at a pH above 7.5 and running the reaction until the desired molar ratio of drug to L-HSA is obtained.

Abstract: 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.

Abstract: 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.