Phosphorylated pyrone analogs and methods

Abstract

The invention relates to phosphorylated polyphenols, phosphorylated flavonoids, and phosphorylated pyrone analogs. Methods and compositions for the modulation of side effects of substances using such phosphorylated compounds are described. Methods and compositions are described for the modulation of blood-tissue barrier (BTB) transporter activity to increase the efflux of drugs and other compounds out of a physiological compartment and into an external environment. In particular, the methods and compositions disclosed herein provide lowered side effects when phosphorylated pyrone analogs are coadministered with therapeutic agents.

1 - 94 . (canceled) 
     
     
         95 . A method for reducing or eliminating a side effect associated with the administration of a therapeutic agent to an animal comprising administering to the animal an effective amount of quercetin-3′-O-phosphate. 
     
     
         96 . The method of  claim 95 , wherein the quercetin-3′-O-phosphate or pharmaceutically acceptable salt has a purity of about 85% to about 100%. 
     
     
         97 . The method of  claim 95 , wherein the quercetin-3′-O-phosphate or pharmaceutically acceptable salt has a purity of greater than about 90%. 
     
     
         98 . The method of  claim 95 , wherein the quercetin-3′-O-phosphate or pharmaceutically acceptable salt has a purity of greater than about 98%. 
     
     
         99 . The method of  claim 95 , wherein the quercetin-3′-O-phosphate or pharmaceutically acceptable salt has a purity of greater than about 99%. 
     
     
         100 . The method of  claim 95 , wherein the quercetin-3′-O-phosphate or pharmaceutically acceptable salt has a purity of greater than about 99.8%. 
     
     
         101 . The method of  claim 95 , wherein the therapeutic agent is an immunosuppressant, antiviral, antibiotic, antineoplastic, amphetamine, antihypertensive, vasodilator, barbiturate, membrane stabilizer, cardiac stabilizer, glucocorticoid, antilipedemic, antiglycemic, cannabinoid, antidipressant, antineuroleptic, antiinfective, immunomodulator or chemotherapeutic agent. 
     
     
         102 . The method of  claim 95 , wherein the therapeutic agent is an immunosuppressant. 
     
     
         103 . The method of  claim 95 , wherein the therapeutic agent is a calcineurin inhibitor. 
     
     
         104 . The method of  claim 95 , wherein the therapeutic agent is tacrolimus, sirolimus, mycophenolate, methadone, cyclosporin, prednisone, voclosporin, oxycodone, gabapentin, pregabalin, hydrocodone, fentanyl, hydromorphone, levorphenol, morphine, methadone, mycophenolate, tramadol, hydromorphine, topiramate, diacetyl morphine, codeine, olanzapine, hydrocortisone, prednisone, sufentanyl, alfentanyl, carbamazapine, lamotrigine, doxepin, or haloperidol. 
     
     
         105 . The method of  claim 95 , wherein the therapeutic agent is tacrolimus, sirolimus, mycophenolate, methadone, cyclosporin, prednisone, or voclosporin. 
     
     
         106 . The method of  claim 95 , wherein the therapeutic agent is tacrolimus. 
     
     
         107 . The method of  claim 95 , wherein the therapeutic agent is cyclosporin. 
     
     
         108 . The method of  claim 95 , wherein the quercetin-3′-O-phosphate or pharmaceutically acceptable salt and the therapeutic agent are administered to the animal separately. 
     
     
         109 . The method of  claim 95 , wherein the quercetin-3′-O-phosphate or pharmaceutically acceptable salt and the therapeutic agent are administered to the animal simultaneously. 
     
     
         110 . The method of  claim 95 , wherein the quercetin-3′-O-phosphate or pharmaceutically acceptable salt is administered to the animal before or concurrently with the administration of the therapeutic agent. 
     
     
         111 . The method of  claim 95 , wherein the side effect is drowsiness, impaired concentration, sexual dysfunction, a sleep disturbance, habituation, dependence, alteration of mood, respiratory depression, nausea, vomiting, lowered appetite, lassitude, lowered energy, dizziness, memory impairment, neuronal dysfunction, neuronal death, visual disturbance, impaired mentation, tolerance, addiction, hallucinations, lethargy, myoclonic jerking, an endocrinopathy, or a combination thereof. 
     
     
         112 . The method of  claim 95 , wherein the side effect is hyperglycemia. 
     
     
         113 . The method of  claim 106 , wherein the side effect is hyperglycemia.