Liposome Drug Delivery of Polycyclic, Aromatic, Antioxidant or Anti-Inflammatory Compounds

Abstract

This invention comprises pharmaceutical compositions for administering a polycyclic, aromatic, antioxidant or anti-inflammatory compound to an animal. Particularly provided are proliposomal compositions that are advantageously used to deliver polycyclic, aromatic, antioxidant or anti-inflammatory compounds to the gastrointestinal tract after oral administration.

1 - 39 . (canceled) 
   
   
       40 . A pharmacological composition in a tablet or capsule comprising a proliposomal preparation, an enteric coating, and a protective coating in between the proliposomal preparation and the enteric coating, wherein the proliposomal preparation consists of at least one phospholipid, a primary aliphatic amine, cholesterol, and one or a plurality of polycyclic aromatic antioxidant or anti-inflammatory compounds. 
   
   
       41 . A pharmacological composition according to  claim 40  wherein the polycyclic aromatic antioxidant or anti-inflammatory compound is cis-stilbene; trans-stilbene; 3-, 4-, or 4′-hydroxy, or (3,4′)- or (4′,5)-dihydroxy cis-stilbene; 3-, 4-, or 4′-hydroxy, or (3,4′)- or (4′,5)-dihydroxy trans-stilbene; carboxylated derivatives of cis-stilbene or trans-stilbene; halogenated derivatives of cis-stilbene or trans-stilbene; resveratrol (trans-3,5,4′-trihydroxystilbene); chrysin (5,7-dihydroxyflavone) or quercetin (3,3′,4′,5,7-pentahydroxyflavone), or biologically-active derivatives thereof. 
   
   
       42 . A pharmacological composition according to  claim 41  wherein the enteric coating is cellulose acetate phthalate or a poly(acrylate, methacrylate) copolymer. 
   
   
       43 . A pharmacological composition according to  claim 41  wherein the protective coating is hydroxypropyl methylcellulose, polyethylene glycol or ethylcellulose. 
   
   
       44 . A pharmacological composition according to  claim 40  wherein the protective coating further comprises a plasticizer. 
   
   
       45 . A pharmacological composition according to  claim 44  wherein the plasticizer is triethylcitrate or polyvinyl pyrrolidine. 
   
   
       46 . A pharmacological composition according to  claim 40  comprising a particle lubricant that is talc, lactose, corn starch, ethyl cellulose, fatty acids or salts thereof, agar, pectin, gelatin or acacia. 
   
   
       47 . A pharmacological composition according to  claim 41  wherein the polycyclic aromatic antioxidant or anti-inflammatory compound is resveratrol, quercetin or chrysin. 
   
   
       48 . A pharmacological composition according to  claim 40  wherein the phospholipid is a phosphatidylcholine, a phosphatidylethanolamine, sphingosine, ceramide, or a mixture thereof. 
   
   
       49 . A pharmacological composition according to  claim 48  wherein the phosphatidylcholine is distearylphosphatidylcholine, dimyristylphosphatidylcholine or a mixture thereof. 
   
   
       50 . A method for increasing the bioavailability of a polycyclic, aromatic antioxidant or anti-inflammatory compound, said method comprising orally administering to a human or an animal in need thereof a pharmaceutical composition according to claim  1 . 
   
   
       51 . A method according to  claim 50  wherein the polycyclic aromatic antioxidant or anti-inflammatory compound is cis-stilbene; trans-stilbene; 3-, 4-, or 4′-hydroxy, or (3,4′)- or (4′,5)-dihydroxy cis-stilbene; 3-, 4-, or 4′-hydroxy, or (3,4′)- or (4′,5)-dihydroxy trans-stilbene; carboxylated derivatives of cis-stilbene or trans-stilbene; halogenated derivatives of cis-stilbene or trans-stilbene; resveratrol (trans-3,5,4′-trihydroxystilbene); chrysin (5,7-dibydroxyflavone) or quercetin (3,3′,4′,5,7-pentahydroxyflavone), or biologically-active derivatives thereof. 
   
   
       52 . A method according to  claim 51  wherein the polycyclic aromatic antioxidant or anti-inflammatory compound is resveratrol, quercetin or chrysin. 
   
   
       53 . A method of preventing coronary heart disease, myocardial infarction, ischemia, stroke, thrombosis, pulmonary embolism, or cancer, said method comprising administering a composition of  claim 40  to human in need thereof. 
   
   
       54 . A method according to  claim 53  wherein the polycyclic aromatic antioxidant or anti-inflammatory compound is cis-stilbene; trans-stilbene; 3-, 4-, or 4′-hydroxy, or (3,4′)-or (4′,5)-dihydroxy cis-stilbene; 3-, 4-, or 4′-hydroxy, or (3,4′)- or (4′,5)-dihydroxy trans-stilbene; carboxylated derivatives of cis-stilbene or trans-stilbene; halogenated derivatives of cis-stilbene or trans-stilbene; resveratrol (trans-3,5,4′-trihydroxystilbene); chrysin (5,7-dihydroxyflavone) or quercetin (3,3′,4′,5,7-pentahydroxyflavone), or biologically-active derivatives thereof. 
   
   
       55 . A method according to  claim 54  wherein the polycyclic aromatic antioxidant or anti-inflammatory compound is resveratrol, quercetin or chrysin. 
   
   
       56 . A method for delivering a polycyclic, aromatic, antioxidant or anti-inflammatory compound to the intestine or colon, said method comprising orally administering to a human or animal in need thereof a said method comprising orally administering to an animal in need thereof a pharmaceutical composition according to  claim 40 . 
   
   
       57 . A method according to  claim 56  wherein the polycyclic aromatic antioxidant or anti-inflammatory compound is cis-stilbene; trans-stilbene; 3-, 4-, or 4′-hydroxy, or (3,4′)-or (4′,5)-dihydroxy cis-stilbene; 3-, 4-, or 4′-hydroxy, or (3,4′)- or (4′,5)-dihydroxy trans-stilbene; carboxylated derivatives of cis-stilbene or trans-stilbene; halogenated derivatives of cis-stilbene or trans-stilbene; resveratrol (trans-3,5,4′-trihydroxystilbene); chrysin (5,7-dihydroxyflavone) or quercetin (3,3′,4′,5,7-pentahydroxyflavone), or biologically-active derivatives thereof. 
   
   
       58 . A method according to  claim 57  wherein the polycyclic aromatic antioxidant or anti-inflammatory compound is resveratrol, quercetin or chrysin.