Liposome Drug Delivery

Abstract

This invention comprises pharmaceutical compositions for administering a biologically active compound to an animal. Particularly provided are proliposomal compositions that are advantageously used to deliver biologically active compounds to the gastrointestinal tract after oral administration.

1 - 13 . (canceled) 
   
   
       14 . A pharmacological composition comprising a proliposomal preparation of a biologically active compound, where the biologically active compound is a nutrient, hormone, nucleic acid, antibiotic drug, enzyme, antigen, antiviral drug, antineoplastic, antiproliferative, peptide or a protein, in a capsule or tablet comprising an enteric coating, a particle lubricant, and a protective coating in between the proliposomal preparation and the enteric coating, wherein the proliposomal preparation comprises a positively charged phospholipid and a neutral lipid, and wherein the protective coating further comprises a plasticizer. 
   
   
       15 . A pharmacological composition according to  claim 14  wherein the enteric coating is cellulose acetate phthalate or a poly(acrylate, methacrylate) copolymer. 
   
   
       16 . A pharmacological composition according to  claim 14  wherein the protective coating is hydroxypropyl methylcellulose, polyethylene glycol or ethylcellulose. 
   
   
       17 . A pharmacological composition according to  claim 14  wherein the neutral lipid is cholesterol. 
   
   
       18 . A pharmacological composition according to  claim 14  wherein the positively charged phospholipid is a phosphatidylcholine, sphingosine, ceramide, or stearylamine. 
   
   
       19 . A pharmacological composition according to  claim 14  wherein the plasticizer is triethylcitrate or polyvinyl pyrrolidine. 
   
   
       20 . A pharmacological composition according to  claim 14  wherein the particle lubricant is talc, lactose, corn starch, ethyl cellulose, fatty acids or salts thereof, agar, pectin, gelatin or acacia. 
   
   
       21 . A pharmacological composition according to  claim 14  wherein the biologically active compound is aspirin, ibuprofen, erythromycin, vasopressin insulin, dideoxyinosine, cyclosporine, taxol, heparin, halofantrine, ethopropazine, griseofulvin, propofol, furosemide, carbamazepine, diazepam, candesartan or cilexetil. 
   
   
       22 . A pharmacological composition according to  claim 14  wherein the neutral lipid is cholesterol and the positively charged phospholipid is a phosphatidylcholine, a phosphatidylethanolamine, sphingosine, ceramide, or stearylamine. 
   
   
       23 . A pharmacological composition according to  claim 22  wherein the phosphatidylcholine is distearylphosphatidylcholine, dimyristylphosphatidylcholine or a mixture thereof. 
   
   
       24 . A method for increasing the bioavailability of a biologically active compound, said method comprising orally administering to a human in need thereof a pharmaceutical composition of  claim 14 . 
   
   
       25 . A method according to  claim 24  wherein the biologically active compound is aspirin, ibuprofen, erythromycin, vasopressin insulin, dideoxyinosine, cyclosporine, taxol, heparin, halofantrine, ethopropazine, griseofulvin, propofol, furosemide, carbamazepine, diazepam, candesartan or cilexetil; the enteric coating is cellulose acetate phthalate or a poly(acrylate, methacrylate) copolymer; the protective coating is hydroxypropyl methylcellulose, polyethylene glycol or ethylcellulose; the plasticizer is triethylcitrate or polyvinyl pyrrolidine; and wherein the particle lubricant is talc, lactose, corn starch, ethyl cellulose, fatty acids or salts thereof, agar, pectin, gelatin or acacia. 
   
   
       26 . A method of treating Crohn's disease, irritable bowel syndrome, celia sprue, diverticulitis, immunoproliferative small intestine disease, liver disease, diseases and disorders of the gall bladder, disorders that are consequent to the removal of the gall bladder, pancreatitis, Schwachman's syndrome, steatorrhea, Whipple's disease, parasitic infection, malabsorption as a consequence of chronic laxative use or abuse, pancreatic enzyme deficiency, disaccharidase deficiency, or defects in fat absorption consequent to surgical gastrectomy or other surgical interventions in the gastrointestinal tract, said method comprising administering a composition of  claim 14  to human in need thereof. 
   
   
       27 . A method according to  claim 26  wherein the biologically active compound is aspirin, ibuprofen, erythromycin, vasopressin insulin, dideoxyinosine, cyclosporine, taxol, heparin, halofantrine, ethopropazine, griseofulvin, propofol, furosemide, carbamazepine, diazepam, candesartan or cilexetil. 
   
   
       28 . A method according to  claim 27 , wherein the enteric coating is cellulose acetate phthalate or a poly(acrylate, methacrylate) copolymer; the protective coating is hydroxypropyl methylcellulose, polyethylene glycol or ethylcellulose; the plasticizer is triethylcitrate or polyvinyl pyrrolidine; and wherein the particle lubricant is talc, lactose, corn starch, ethyl cellulose, fatty acids or salts thereof, agar, pectin, gelatin or acacia. 
   
   
       29 . A method according to  claim 28  wherein the neutral lipid is cholesterol and the positively charged phospholipid is a phosphatidylcholine, a phosphatidylethanolamine, sphingosine, ceramide, or stearylamine. 
   
   
       30 . A method according to  claim 29 , wherein the phosphatidylcholine is distearylphosphatidylcholine, dimyristylphosphatidylcholine or a mixture thereof. 
   
   
       31 . A method for delivering a biologically active compound to the intestine or colon, said method comprising orally administering to human in need thereof a composition of  claim 14 . 
   
   
       32 . A method according to  claim 31  wherein the biologically active compound is aspirin, ibuprofen, erythromycin, vasopressin insulin, dideoxyinosine, cyclosporine, taxol, heparin, halofantrine, ethopropazine, griseofulvin, propofol, furosemide, carbamazepine, diazepam, candesartan or cilexetil. 
   
   
       33 . A method according to  claim 32 , wherein the enteric coating is cellulose acetate phthalate or a poly(acrylate, methacrylate) copolymer; the protective coating is hydroxypropyl methylcellulose, polyethylene glycol or ethylcellulose; and the plasticizer is triethylcitrate or polyvinyl pyrrolidine; and wherein the particle lubricant is talc, lactose, corn starch, ethyl cellulose, fatty acids or salts thereof, agar, pectin, gelatin or acacia. 
   
   
       34 . A method according to  claim 33  wherein the neutral lipid is cholesterol and the positively charged phospholipid is a phosphatidylcholine, a phosphatidylethanolamine, sphingosine, ceramide, or stearylamine. 
   
   
       35 . A method according to  claim 34 , wherein the phosphatidylcholine is distearylphosphatidylcholine, dimyristylphosphatidylcholine or a mixture thereof.