Da Volterra

Assistance Publique-hopitaux De Paris

Université Paris Diderot-Paris 7

Other

Centre National De La Recherche Scientifique

Université Paris-Sud 11

Centre Nationale De La Recherche Scientifique

Institut Pasteur

Antoine Andremont

Elias Fattal

Nicolas Tsapis

Patrick Couvreur

Patrice Courvalin

Sandrine Bourgeois

Helene-Celine Huguet

Helene Huguet

Etienne Ruppe

Hélène-Céline Huguet

Raymond Ruimy

Sylvie Bremont

Tsapis Nicolas

Hélène Huguet

Fattal Elias

Compositions which deliver adsorbents, alone or in combination with active drug 'degrading molecules,' in a site-specific manner to the intestine, and which eliminate or at least lower the concentration of residual unwanted material within the intestine, and methods of treatment using the compositions, are disclosed. The compositions are ideally designed to specifically release the adsorbents in a programmed manner at a specific site of the intestinal tract. Programmed delivery prevents adsorbents from interfering with the normal absorption process of a given molecule after oral absorption, until it reaches the lower part of the small intestine. The compositions can be used to adsorb, and therefore remove, any residual drug, metabolite thereof, or bacterial toxin after oral or parenteral administration which would otherwise cause adverse effects in the lower intestine and/or colon.

Site-specific intestinal delivery of adsorbents, alone or in combination with degrading molecules

Drug delivery systems for reducing the quantity of residual antibiotics reaching the colon following oral or parenteral antibiotic therapy, and for delivering metallo-dependent enzymes, and methods of use thereof, are disclosed. The drug delivery systems include pectin beads that encapsulate the active agent (which can be a metallo-dependent enzyme). The pectin is crosslinked with zinc or other divalent cations, and the pectin beads are coated with Eudragit&#xae;-type polymers. The delivery of the active agent can be modulated to occur at various pre-selected sites of delivery within the intestinal tract. A stable metallo-dependent enzyme formulation can be delivered to the lower intestine or colon. The use of zinc cations to crosslink the pectin is particularly preferred when the metallo-dependent enzymes are zinc dependent, where other cationic used to gel the pectin beads might adversely affect the activity of such metallo-dependent enzymes.

Colonic delivery of metallo-dependent enzymes

Orally administrable, site-specific (colonic), particulate delivery systems including adsorbents are disclosed. When delivered specifically to the colon, they can remove various substances present in, or as they reach, the colon. Methods of treatment using the delivery systems, and methods of preparing the delivery systems, are also disclosed. The particulate delivery systems are based on adsorbent matrices encapsulated into and/or onto particles, which selectively deliver the adsorbents to the colon. Representative drug delivery devices include pectin beads, which can optionally be crosslinked with metal ions such as zinc and/or calcium. The delivery system protects the adsorbent and prevents its adsorbing effect in the upper gastro-intestinal (GI) tract. When the particles are made from pectin, and the beads are administered to the colon, specific pectinolytic enzymes in the colon degrade the pectin, allowing the adsorbent to be released and to be fully active. Antibiotics, toxins, and other absorbable substances present in the colon will then be inactivated by adsorption into or onto the adsorbent.

Colonic delivery of adsorbents

Compositions which deliver adsorbents, alone or in combination with active drug 'degrading molecules,' in a site-specific manner to the intestine, and which eliminate or at least lower the concentration of residual unwanted material within the intestine, are disclosed. Methods of treatment using the compositions are also disclosed. The material to be eliminated can include residual active antibiotics, metabolites, bacterial or other toxins, and drugs which cause side effects in the gastrointestinal tract. The adsorbents can be formulated in capsules, tablets or any acceptable pharmaceutical composition, and are ideally designed to specifically release the adsorbents in a programmed manner at a specific site of the intestinal tract. The programmed delivery prevents adsorbents from interfering with the normal absorption process of a given molecule after oral absorption, until it reaches the lower part of the small intestine. The compositions can be used to adsorb, and therefore remove, any residual drug, metabolite thereof, or bacterial toxin after oral or parenteral administration which would otherwise cause adverse effects in the lower intestine and/or colon.

The invention concerns multiparticulate galenic formulations for oral administration and designed for colon targeted delivery of active principles selected from the group comprising enzymes capable of inactivating macrolides and the like, enzymes capable of inactivating quinolones and &#x3b2;-lactamases.

Galenic formulation for colon-targeted delivery of active ingredients

Forms of colonic delivery suited to be used orally and designed for colonic delivery of active ingredients selected from the group comprising enzymes capable of inactivating macrolide antibiotics and related compounds, enzymes capable of inactivating quinolones, and &#x3b2;-lactamases.

Galenic pectinate formulation for colon-targeted delivery of antibiotic-inactivating enzymes and method of use thereof

Growing community of inventors

Malakoff, France

Antoine Andremont