Method of using cyclodextrin

Abstract

Described are methods for using cyclodextrin to treat, inhibit, prevent, ameliorate, or cure diabetes or conditions relating to diabetes.

1 . A method for treating or reducing the progression of a condition selected from the group consisting of diabetes (type 1), diabetes (type 2), prediabetes, obesity, metabolic syndrome, diabetic nephropathy, diabetic kidney disease, obesity related glomerulopathy, diabetic neuropathy, diabetic retinopathy, diabetes-related microvascular complication, diabetes-related macrovascular complications, atherosclerosis, peripheral vascular disease, coronary artery diseases, congestive heart failure, cardiac hypertrophy, myocardial infarction, endothelial dysfunction and hypertension, stroke, cerebrovascular accident, myocardial infarction, heart attack, cardiovascular accidents, fatty liver, steatohepatitis, NASH, and insulin resistance in a patient in need thereof, said method comprising administering to the patient an effective amount of a compound selected from the group consisting of a cyclodextrin as an active agent, a modulator of ABCA 1, a recombinant ApoA 1, an ApoA 1 mimetic peptide, a modulator of SMPDL3b, and an HDL mimetic. 
     
     
         2 . The method of  claim 1  wherein the compound modulates a cellular mechanism to redistribute or reduce cellular cholesterol accumulation, said mechanism selected from the group consisting of inhibiting a cellular influx mechanism, increasing a cellular efflux mechanism, modulating ABCA 1, and modulating a sphingolipid enzyme. 
     
     
         3 . The method of  claim 1  wherein the cell is in a central or peripheral organ affected by or responsible for development of diabetes. 
     
     
         4 . The method of  claim 3  wherein the organ is selected from the group consisting of pancreas and kidney. 
     
     
         5 . The method of  claim 1  wherein the compound further interferes with a cellular cholesterol synthetic pathway. 
     
     
         6 . (canceled) 
     
     
         7 . The method of  claim 1  wherein the compound is hydroxypropyl beta cyclodextrin. 
     
     
         8 . The method of  claim 1  wherein the compound is administered by a route selected from the group consisting of intramuscular, intraperitoneal, intravenous (systemic), subcutaneous, transdermal, oral, rectal, inhalation, topical, and intranasal. 
     
     
         9 . The method of  claim 8  wherein the administration route is subcutaneous. 
     
     
         10 . The method of  claim 1  wherein the compound is administered at a dose ranging from about 4-20,000 mg/kg/week. 
     
     
         11 . The method of  claim 1  wherein the compound is administered at least one time per week up to about three times per day. 
     
     
         12 . The method of  claim 1  wherein the compound is administered as a composition consisting essentially of at least one cyclodextrin and, optionally, at least one pharmaceutically acceptable excipient or vehicle. 
     
     
         13 . The method of  claim 1  wherein the compound is administered as a composition comprising a cyclodextrin and a second active agent which is not a cyclodextrin. 
     
     
         14 . The method of  claim 13 , wherein the second active agent is selected from the group consisting of an antidiabetic agent, a cholesterol biosynthesis inhibitor, a cholesterol absorption inhibitor, a bile acid sequestrant, niacin or niacin derivative, a fibrate, a cholesteryl ester transferase protein, and an acetyl-coenzyme A acetyltransferase inhibitor, an ABCA 1 modulator, a sphingolipid enzyme modulator, a recombinant ApoA1 or ApoA1 mimetic peptide, a HDL mimetic, a liver X receptor agonist, an immunosuppressive agent, insulin, sulphonylurea, gliptin, metformin, thiazolidinedione, insulin sensitizer, chromium picolinate, an incretin analogue, a DPP4 inhibitor, a VEG-interfering agent, a growth factor, an anti-inflammatory, a vitamin D derivative, a RAS system blocker, an aldosterone blocker, and a biologic. 
     
     
         15 . (canceled) 
     
     
         16 . A composition for treating, inhibiting, preventing, or ameliorating a symptom or related condition caused by cellular accumulation of cholesterol, wherein the composition consists essentially of an effective amount of a cyclodextrin as an active pharmaceutical agent, and optionally one or more pharmaceutically acceptable excipients or vehicles. 
     
     
         17 . The composition of  claim 16 , wherein the composition further comprises a second active pharmaceutical agent which is not a cyclodextrin. 
     
     
         18 . The composition of  claim 17 , wherein the second active ingredient is selected from the group consisting of an antidiabetic agent, a cholesterol biosynthesis inhibitor, a cholesterol absorption inhibitor, a bile acid sequestrant, niacin or niacin derivative, a fibrate, a cholesteryl ester transferase protein, and an acetyl-coenzyme A acetyltransferase inhibitor, an ABCA 1 modulator, a sphingolipid enzyme modulator, a recombinant ApoA1 or ApoA1 mimetic peptide, a HDL mimetic, a liver X receptor agonist, an immunosuppressive agent, insulin, sulphonylurea, gliptin, metformin, thiazolidinedione, insulin sensitizer, chromium picolinate, an incretin analogue, a DPP4 inhibitor, a VEG-interfering agent, growth factor, an anti-inflammatory, a vitamin D derivative, a RAS system blocker, an aldosterone blocker, and a biologic. 
     
     
         19 . An article of manufacture comprising a composition in a container, said composition comprising at least one cyclodextrin as an active agent, wherein the container is packaged with written instruction for use of the composition for treatment of a condition caused by, or symptom resulting from, cellular or plasma membrane accumulation of lipid. 
     
     
         20 . The article of manufacture of  claim 19 , wherein the condition is selected from diabetes (type 1), diabetes (type 2), prediabetes, obesity, metabolic syndrome, diabetic nephropathy, diabetic kidney disease, obesity related glomerulopathy, diabetic neuropathy, diabetic retinopathy, diabetes related microvascular complication, diabetes related macrovascular complications, atherosclerosis, peripheral vascular disease, coronary artery diseases, congestive heart failure, cardiac hypertrophy, myocardial infarction, endothelial dysfunction and hypertension, stroke, cerebrovascular accident, myocardial infarction, heart attack, cardiovascular accidents, fatty liver, steatohepatitis, NASH, and insulin resistance. 
     
     
         21 . The article of manufacture of  claim 20  wherein the cellular or plasma membrane lipid is cholesterol.