University System of Maryland

Cristalia Productos Quimicos Farmaceuticos Ltda.

Roberto Takashi Sudo

Edson X Albuquerque

Yasco Aracava

Gisele Zapata Sudo

Newton Goncalves De Castro

Francois Germain Noel

Eliezer J De Barreiro

Claudia Lucia Martins Da Silva

Valter F T Russo

Wagner Monteiro Cintra

Patricia Dias Fernandes

Carlos Alberto Manssour Fraga

Elisa M S Russo

Paulo De Assis Melo

Ana Luisa Palhares De Miranda

The present invention describes a new method for the separation of bupivacaine enantiomers consisting in a continuous separation process performed without heating, by the selective precipitation of their diastereomeric salts with tartaric acid. This heatless process avoids the degradation of the reagents granting a continuous process feature to the procedure. Another embodiment of the present invention is related to the enantiomeric manipulation of bupivacaine enantiomers in order to obtain pharmaceutical compositions presenting several enantiomeric excess of levobupivacaine to quantify and determinate the role of the dextrobupivacaine on its anesthetic and cardiotoxic effects. These enantiomeric manipulated compositions showed to present an expressive improvement on its anesthetic properties that had shown to be similar to racemic bupivacaine presenting a cardiotoxic profile similar to enantiomeric pure levobupivacaine.

Use of a non-racemic mixture of bupivacaine enantiomers, for improving the anesthesia profile

The invention discloses a compound having the formula (I) wherein Ris selected from the group consisting of hydrogen, alkyl of 1 to 6 carbon atoms, unsubstituted phenyl, and substituted phenyl; Ris selected from the group consisting of H, alkene, un-substituted phenol, and substituted phenyl; and pharmaceutically acceptable salts thereof, having digitalis-like properties. The invention further discloses a novel method to synthesize 3,4-methylenedioxybenzoyl-2-thienylhydrazone (LASSBio-294). LASSBio-294 produces positive inotropic effect on cardiac and skeletal muscle. The invention is useful for the treatment of congestive heart failure and muscle fatigue. It lacks toxic effects seen in digitalis glycosides.

Thienylhydrazon with digitalis-like properties (positive inotropic effects)

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Rio de Janeiro, Brazil

Roberto Takashi Sudo