# US 11,304,902 B2 · Pharmaceutical compositions, preparation and uses thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,304,902 B2 - Document ID: US11304902B2 - Status: Granted - Kind: B2 - Application number: 15/529,097 - Filed: 2015-11-24 - Published: 2017-09-14 - Granted: 2022-04-19 - Earliest claimed: 2014-11-25 - Assignees: Curadigm SAS - Applicants: Curadigm SAS - Inventors: Agnes Pottier; Matthieu Germain; Laurence Poul; Marion Paolini; Marie-Edith Meyre - Web page: https://patentgrep.com/patent/US11304902B2 ## CPC - A61K 9/1271: Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers (liposomes as conjugates {A61K47/6911}) - A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)} - A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration} - A61K 9/51: Nanocapsules; {Nanoparticles; (nanotubes A61K9/0092; polymeric micelles A61K9/1075; polymersomes A61K9/1273; pure drug nanoparticles A61K9/14; drug nanoparticles with adsorbed surface modifiers A61K9/141; conjugates, e.g. between drug and non-active nanoparticles, A61K47/50; preparations for in vivo diagnosis A61K49/00; with radioactive substances A61K51/00)} - A61K 9/513: {Organic macromolecular compounds; Dendrimers} - A61K 31/37: Coumarins, e.g. psoralen - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61P 17/06: Antipsoriatics - A61P 31/10: Antimycotics - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - C07D 491/14: Ortho-condensed systems - A61K 2121/00: Preparations for use in therapy - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) ## 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. ## Claims ### Claim 1 A therapeutic or prophylactic method comprising a step of administering at least one pharmaceutical compound to a subject in need thereof and a distinct step of administering at least one biocompatible nanoparticle to said subject, wherein the at least one biocompatible nanoparticle comprises bergamottin, 6′,7′-dihydroxybergamottin (DHB) or a mixture thereof, the longest dimension of said at least one biocompatible nanoparticle is at least 4 nm and less than 100 nm, the at least one biocompatible nanoparticle is not used as the therapeutic or prophylactic compound, wherein the at least one pharmaceutical compound is a substrate of the human CYP3A4 and/or CYP2B6 enzymes, and wherein said at least one biocompatible nanoparticle is administered separately to the subject between 5 minutes and about 72 hours before the at least one pharmaceutical compound, the at least one biocompatible nanoparticle and the at least one pharmaceutical compound being both administered to the subject through an intravenous (IV) injection route. ### Claim 2 (depends on 1) The method according to claim 1, wherein the administration of the biocompatible nanoparticle(s) and of the at least one pharmaceutical compound allows a reduction of at least 20% of the administered at least one pharmaceutical compound therapeutic dose when compared to the standard therapeutic dose of said at least one pharmaceutical compound while maintaining the same bioavailability. ### Claim 3 (depends on 1) The method according to claim 1, wherein the at least one nanoparticle is cleared from the subject to whom it has been administered within a period of one hour and six weeks after its administration to a subject in need of the at least one pharmaceutical compound. ### Claim 4 (depends on 1) The method according to claim 1, wherein said at least one pharmaceutical compound is selected from docetaxel, doxorubicin, paclitaxel, aprepitant, budesonide, buspirone, conivaptan, darifenacin, darunavir, dasatinib, dronedarone, eletriptan, eplerenone, everolimus, imatinib, indinavir, fluticasone, lopinavir, lurasidone, maraviroc, midazolam, nilotinib, nisoldipine, quetiapine, saquinavir, sildenafil, simvastatin, sirolimus, tolvaptan, tipranavir, triazolam, vardenafil and efavirenz. ### Claim 5 (depends on 1) The method according to claim 1, wherein said at least one pharmaceutical compound is docetaxel or paclitaxel. ### Claim 6 (depends on 5) The method according to claim 5, wherein said at least one pharmaceutical compound is docetaxel. ### Claim 7 (depends on 5) The method according to claim 5, wherein said at least one pharmaceutical compound is paclitaxel. ### Claim 8 (depends on 1) The method according to claim 1, wherein the at least one biocompatible nanoparticle comprises bergamottin. ### Claim 9 (depends on 1) The method according to claim 1, wherein the at least one biocompatible nanoparticle comprises 6′,7′-dihydroxybergamottin (DHB). ### Claim 10 (depends on 1) The method according to claim 1, wherein the at least one biocompatible nanoparticle comprises a mixture of bergamottin and 6′,7′-dihydroxybergamottin (DHB). ### Claim 11 (depends on 1) The method according to claim 1, wherein the at least one biocompatible nanoparticle further comprises retinol. ### Claim 12 A therapeutic or prophylactic method comprising a step of administering at least one pharmaceutical compound to a subject in need thereof and a distinct step of administering at least one biocompatible nanoparticle to said subject, wherein the at least one biocompatible nanoparticle comprises bergamottin, 6′,7′-dihydroxybergamottin (DHB) or a mixture thereof, the longest dimension of said at least one biocompatible nanoparticle is at least 4 nm and less than 100 nm, the at least one biocompatible nanoparticle is not used as the therapeutic or prophylactic compound, wherein the least one pharmaceutical compound is a substrate of the human CYP3A4 and/or CYP2B6 enzymes, and wherein said at least one biocompatible nanoparticle is administered separately to the subject between 5 minutes and about 72 hours before the at least one pharmaceutical compound, the at least one biocompatible nanoparticle and the at least one pharmaceutical compound being both administered to the subject through an intravenous (IV) injection route, and wherein the method further comprises a step of administering a second biocompatible nanoparticle comprising at least one natural compound which is an inhibitor of a human CYP enzyme, the longest dimension of the second biocompatible nanoparticle being of at least 4 nm and less than 100 nm, and wherein the at least one (first) and/or second biocompatible nanoparticle(s) comprise(s) an agent enhancing nanoparticle(s)′ recognition by enterocytes and/or by hepatocytes. ### Claim 13 (depends on 12) The method according to claim 12, wherein the at least one (first) and/or the second biocompatible nanoparticle comprises at least one inhibitor of a human CYP enzyme and said inhibitor is encapsulated in, trapped in, absorbed in, adsorbed on, linked on, conjugated to, attached to or bound to the at least one and/or to the second nanoparticle. ### Claim 14 (depends on 12) The method according to claim 12, wherein the first and second biocompatible nanoparticles are administered separately in an additional distinct step, or simultaneously, in a subject in need of the at least one pharmaceutical compound, and before said at least one pharmaceutical compound. ### Claim 15 (depends on 12) The method according to claim 12, wherein each of the at least one (first) and/or second biocompatible nanoparticles is further covered with a biocompatible coating. ### Claim 16 (depends on 12) The method according to claim 12, wherein the agent enhancing the nanoparticle(s)′ recognition by hepatocytes comprises a saccharide. ### Claim 17 (depends on 12) The method according to claim 12, wherein the at least one biocompatible nanoparticle comprises bergamottin. ### Claim 18 (depends on 12) The method according to claim 12, wherein the at least one biocompatible nanoparticle comprises 6′,7′-dihydroxybergamottin (DHB). ### Claim 19 (depends on 12) The method according to claim 12, wherein the at least one biocompatible nanoparticle comprises a mixture of bergamottin and 6′,7′-dihydroxybergamottin (DHB).