Pharmaceutical compositions, preparation and uses thereof

Inventors

Pottier, Agnes • Germain, Matthieu • Poul, Laurence • PAOLINI, MARION • Meyre, Marie-Edith

Assignees

Nanobiotix SA

Abstract

The present disclosure generally relates to the field of medicine. The present invention more specifically relates to a pharmaceutical composition comprising the combination of (i) at least one biocompatible nanoparticle comprising, or consisting in, at least one natural compound which is an inhibitor of a human CYP enzyme, the longest dimension of said nanoparticle being of at least 4 nm and less than 100 nm, and (ii) at least one compound of interest, typically at least one pharmaceutical compound, to be administered to a subject in need of such at least one compound of interest, wherein the combination of the at least one biocompatible nanoparticle and of the at least one compound of interest potentiates the at least one compound of interest's bioavailability. The at least one biocompatible nanoparticle is to be administered to the subject separately from the at least one compound of interest (preferably before), typically with an interval of between at least about 5 minutes (preferably more than about 5 minutes) and about 72 hours.

Core Innovation

The invention relates to pharmaceutical compositions and therapeutic or prophylactic methods that administer at least one pharmaceutical compound and, in a distinct step, at least one biocompatible nanoparticle comprising natural CYP-inhibitor compounds. The biocompatible nanoparticle comprises bergamottin, 6′,7′-dihydroxybergamottin (DHB), or a mixture thereof, and is characterized by a nanoparticle longest dimension of at least 4 nm and less than 100 nm.

In the method, the biocompatible nanoparticle is administered separately from the pharmaceutical compound through an intravenous (IV) injection route. The nanoparticle is administered between 5 minutes and about 72 hours before the pharmaceutical compound, such that bioavailability is potentiated for the pharmaceutical compound.

The invention also includes embodiments with a second biocompatible nanoparticle, where the second nanoparticle comprises at least one natural compound that is an inhibitor of a human CYP enzyme. Additionally, the biocompatible nanoparticles may comprise an agent enhancing nanoparticle recognition by enterocytes and/or by hepatocytes, and the recognition-enhancing agent is described as comprising saccharides for hepatocyte/enterocyte recognition.

Example embodiments include hyaluronic acid-coated nanoparticles, optional second nanoparticles, and sequential administration. The document describes in vitro and in vivo evidence using DHB micelles with docetaxel, including HepaRG metabolism inhibition and improved survival in an HT-29 tumor xenograft mouse model.

Claims Coverage

The partial content includes two independent claims covering a therapeutic or prophylactic method using distinct IV administration steps for a CYP3A4/CYP2B6 substrate pharmaceutical compound and a biocompatible nanoparticle comprising bergamottin and/or 6′,7′-dihydroxybergamottin (DHB), administered within a 5 minute to about 72 hour window before the pharmaceutical compound. The second independent claim further adds an additional second biocompatible nanoparticle and recognition-enhancing functionality for enterocytes and/or hepatocytes.

Overall, the claims cover IV sequential administration in which a biocompatible nanoparticle comprising bergamottin and/or DHB (not used as the therapeutic/prophylactic compound) is given separately within a 5 minute to about 72 hour window before a CYP3A4/CYP2B6 substrate pharmaceutical compound, using nanoparticles sized with a longest dimension of at least 4 nm and less than 100 nm, and optionally adding a second CYP-inhibitor nanoparticle and enterocyte/hepatocyte recognition-enhancing agents.

Stated Advantages

Documented Applications