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 reducing lipid content in a cell or plasma membrane of a cell in a patient suffering from a condition 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, said method comprising administering to the patient an effective amount of a compound which reduces cellular or plasma membrane lipid content for treating, inhibiting, preventing, or ameliorating said condition, or a symptom or sign thereof. 
     
     
         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 ABCA1, 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 . The method of  claim 1  wherein the compound is selected from the group consisting of a cyclodextrin, a derivative or analog of a cyclodextrin, a modulator of ABCA1, a recombinant ApoA1, an ApoA1 mimetic peptide, a modulator of SMPDL3b, and an HDL mimetic. 
     
     
         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 2-20 mg/kg/day to about 4,000-20,000 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 or derivative or analog 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 or derivative or analog of a cyclodextrin, and a second active ingredient which is not a cyclodextrin or derivative or analog of a cyclodextrin. 
     
     
         14 . The method of  claim 13 , 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 ABCA1 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, incretin analogue, DPP4 inhibitor, VEG-interfering agent, growth factor, antinflammatory, vitamin D derivative, RAS system blocker, an aldosterone blocker, and a biologic. 
     
     
         15 . A composition for treating, inhibiting, preventing, or ameliorating a symptom or related condition caused by cellular accumulation of cholesterol said composition comprising an effective amount of a cyclodextrin or derivative of cyclodextrin. 
     
     
         16 . The composition of  claim 15 , wherein the composition consists essentially of one or more cyclodextrin or derivative of cyclodextrin as an active pharmaceutical ingredient in the composition and optionally one or more pharmaceutically acceptable excipient or vehicle. 
     
     
         17 . The composition of  claim 15 , wherein the composition further comprises a second active pharmaceutical ingredient which is not a cyclodextrin or a derivative of 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 ABCA1 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, incretin analogue, DPP4 inhibitor, VEG-interfering agent, growth factor, antinflammatory, vitamin D derivative, 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 or a derivative of a cyclodextrin, 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.