Inhibitors and enhancers of uridine diphosphate-glucuronosyltransferase 2b (ugt2b)

Abstract

A UGT2B inhibitor capable of increasing the bio-availability of a drug, is a compound in a free base or a pharmaceutically acceptable salt form that is selected from the group consisting of: capillarisin, isorhamnetin,β-naphthoflavone, α-naphthoflavone, hesperetin, terpineol, (+)-limonene, β-myrcene, swertiamarin, eriodictyol, cineole, apigenin, baicalin, ursolic acid, isovitexin, lauryl alcohol, puerarin, trans-cinnamaldehyde, 3-phenylpropyl acetate, isoliquritigenin, paeoniflorin, gallic acid, genistein, glycyrrhizin, protocatechuic acid, ethyl myristate, umbelliferone, PEG (Polyethylene glycol) 400, PEG 2000, PEG 4000, Tween 20, Tween 60, Tween 80, BRIJ® 58, BRIJ® 76, Pluronic® F68, Pluronic® F127, and a combination thereof. A UGT2B enhancer capable of enhancing a clearance rate of morphine-like analgesic agents, is a compound in a free base or a pharmaceutically acceptable salt form that is selected from the group consisting of: nordihydroguaiaretic acid, wogonin, trans-cinnamic acid, baicalein, quercetin, daidzein, oleanolic acid, homoorientin, hesperetin, narigin, neohesperidin, (+)-epicatechin, hesperidin, liquiritin, eriodictyol, formononetin, quercitrin, genkwanin, kaempferol, isoquercitrin, (+)-catechin, naringenin, daidzin, (−)-epicatechin, luteolin-7-glucoside, ergosterol, rutin, luteolin, ethyl myristate, apigenin, 3-phenylpropyl acetate, umbelliferone, glycyrrhizin, protocatechuic acid, poncirin, isovitexin, 6-gingerol, cineole, genistein, trans-cinnamaldehyde, and a combination thereof.

What is claimed is: 
     
         1 . A pharmaceutical composition capable of increasing a bio-availability of morphine-like analgesic agents, including:
 an active ingredient as an Uridine diphosphate (UDP)-glucuronosyltransferases 2B (UGT2B) inhibitor that is a compound in a free base or a pharmaceutically acceptable salt form that is selected from the group consisting of: swertiamarin, ursolic acid, 3-phenylpropyl acetate, isoliquritigenin, paeoniflorin, gallic acid, glycyrrhizin, protocatechuic acid, ethyl myristate, PEG (Polyethylene glycol) 400, PEG 2000, PEG 4000, Tween 20, Tween 60, polyoxyethylene acyl ether (BRIJ 58), polyoxyethylene 10 stearyl ether (BRIJ 76), Polyethylene-Polypropylene Glycol (Pluronic F68), and Poloxamer 407 (Pluronic F127);   a pharmaceutically effective amount of morphine-like analgesic agents including at least one selected from the group consisting of: naloxone, nalorphine, oxymorphone, hydromorphone, dihydromorphine, codeine, naltrindole, nalbuphine and buprenorphine; and   a pharmaceutically acceptable inert ingredient.   
     
     
         2 . A method for increasing an oral bioavailability of morphine-like analgesic agents in a patient, comprising:
 orally administering a pharmaceutically effective amount of Uridine diphosphate (UDP)-glucuronosyltransferases 2B (UGT2B) inhibitor and a pharmaceutically effective amount of morphine-like analgesic agent which is metabolized by UGT2B to said patient in need thereof,   wherein said UGT2B inhibitor includes at least one selected from the group consisting of: swertiamarin, ursolic acid, 3-phenylpropyl acetate, isoliquritigenin, paeoniflorin, gallic acid, glycyrrhizin, protocatechuic acid, ethyl myristate, PEG (Polyethylene glycol) 400, PEG 2000, PEG 4000, Tween 20, Tween 60, polyoxyethylene acyl ether (BRIJ 58), polyoxyethylene 10 stearyl ether (BRIJ 76), Polyethylene-Polypropylene Glycol (Pluronic F68), Poloxamer 407 (Pluronic F127), and trans-cinnamaldehye; and   wherein said morphine-like agents which is at least one selected from the group consisting of: naloxone, nalorphine, oxymorphone, hydromorphone, dihydromorphone, codeine, nalbuphine and buprenorphine.