Plant steroids and uses thereof

Abstract

The invention relates to a drug conjugate including a drug and a plant steroid. The drug conjugate may target the drug for intestinal cell delivery, and thus may be used to treat diseases, including intestinal diseases, or to affect intestinal metabolism. The invention therefore also relates to treating intestinal diseases and affecting intestinal metabolism with the drug conjugate.

1 . A drug conjugate of formula (I),
   D-L-P  (I)
   wherein   D is a drug constituent;   L is a linkage; and   P is a plant steroid constituent.   
     
     
         2 . The compound of  claim 1 , wherein D is prednisone. 
     
     
         3 . A drug conjugated according to  claim 1 , selected from the group consisting of:
 prednisolone stigmasteroltrisethyleneglycolalcohol succinate;   prednisolone stigmasterol succinate; and   prednisolone stigmasteroltrisethyleneglycol acetate.   
     
     
         4 . The drug conjugate of  claim 1 , wherein P is a phytosterol or phytostanol constituent. 
     
     
         5 . The drug conjugate of  claim 4 , wherein P is stigmasterol, campesterol, 24(S),25-epoxycholesterol, or 5-6-epoxycampesterol. 
     
     
         6 . The drug conjugate of  claim 1 , wherein D is selected from the group consisting of an anti-inflammatory drug, a glucocorticoid, a LXR agonist, a TNFa inhibitor, a NF-KB inhibitor or agonist, a selective COX-2 inhibitor, a non-selective non-steroidal anti-inflammatory drug (NSAID), methotrexate, leflunomide, mesalamine, balsalaside, osalazine, sulfasalazine, an amino salicylate, cyclosporine, mercaptopurine, azathioprine, atropine, a microsomal triglyceride transfer protein (MTP) inhibitor, an acyl CoA:cholesterol acyltransferase-2 (ACAT 2) inhibitor, a farnesoid X receptor (FXR) agonist, a diacylglycerol actyltransferase (DGAT) inhibitor, a glucagon-like peptide-1 (GLP-1) agonist, an ileal bile acid transport (IBAT) inhibitor, an antibiotic, and an antiviral. 
     
     
         7 . The drug conjugate of  claim 6 , wherein D is a glucocorticoid or a LXR agonist constituent. 
     
     
         8 . The drug conjugate of  claim 7 , where the glucocorticoid is budesonide and the LXR agonist is GW-3965 or TO-901317. 
     
     
         9 . The drug conjugate of  claim 1 , wherein L is a bond. 
     
     
         10 . The drug conjugate of  claim 1 , wherein L comprises at least one chemical functional group selected from the group consisting of an ether, amide, sulfonamide, and ester. 
     
     
         11 . The drug conjugate of  claim 1 , wherein L comprises at least 3 atoms. 
     
     
         12 . The drug conjugate of  claim 11 , wherein L comprises at least 10 atoms. 
     
     
         13 . A drug conjugate according to  claim 1 , selected from the group consisting of:
 a campesterol/budesonide drug conjugate;   a 24(S),25-epoxycholesterol/budesonide drug conjugate;   a campesterol/GW-3965 drug conjugate;   a campesterol/TO-901317 drug conjugate;   a 24(S),25-epoxycholesterol/GW-3965 drug conjugate; and   a 24(S),25-epoxycholesterol/TO-901317 drug conjugate.   
     
     
         14 . A compound comprising a plant steroid and a drug, wherein the plant steroid is attached to the drug. 
     
     
         15 . The compound of  claim 14 , wherein the attachment is a conjugated bond or an amine bond. 
     
     
         16 . The compound of  claim 14 , wherein the drug is selected from the group consisting of an anti-inflammatory drug, a glucocorticoid, a LXR agonist, a TNFa inhibitor, a NF-κB inhibitor or agonist, a selective COX-2 inhibitor, a non-selective non-steroidal anti-inflammatory drug (NSAID), methotrexate, leflunomide, mesalamine, balsalaside, osalazine, sulfasalazine, an amino salicylate, cyclosporine, mercaptopurine, azathioprine, atropine, a microsomal triglyceride transfer protein (MTP) inhibitor, an acyl CoA:cholesterol acyltransferase-2 (ACAT 2) inhibitor, a farnesoid X receptor (FXR) agonist, a diacylglycerol actyltransferase (DGAT) inhibitor, a glucagon-like peptide-1 (GLP-1) agonist, an ileal bile acid transport (IBAT) inhibitor, an antibiotic, and an antiviral. 
     
     
         17 . The compound of  claim 16 , wherein the drug is prednisone. 
     
     
         18 . The compound of  claim 14 , wherein the plant steroid is a sterol selected from the group consisting of a phytosterol and a phytostanol. 
     
     
         19 . The compound of  claim 18 , wherein the sterol is selected from the group consisting of stigmasterol, brassicasterol, campestenol, and campesterol. 
     
     
         20 . A compound comprising cholesterol and a drug, wherein the cholesterol is attached to the drug. 
     
     
         21 . A method for lowering cholesterol levels, comprising administering an oxyphytostanol to a mammal in need thereof.