Controlled release lipoic acid

Abstract

A controlled release formulation of lipoic acid is disclosed. The lipoic acid is combined with excipient materials in such a way that those materials provide for gradual release of the lipoic acid in a manner which makes it possible to substantially increase the period of time over which therapeutic levels of lipoic acid are maintained relative to a quick release formulation. These features make it possible to use lipoic acid to reduce serum glucose levels and maintain those levels over time thereby obtaining a range of desired therapeutic results.

1 .- 20 . (canceled)  
     
     
         21 . A controlled release oral dosage formulation, comprising: 
 a therapeutically effective amount of an orally active antidiabetic chosen from a sulfonylurea, a biguanide and a thiazolidinedione;    a therapeutically effective amount of lipoic acid; and    an excipient material.    
     
     
         22 . The formulation of  claim 21 , wherein the formulation is characterized by releasing the lipoic acid in a manner so as to increase a period of time over which a therapeutic level of lipoic acid is maintained as compared to a quick release formulation  
     
     
         23 . The formulation of  claim 22 , wherein the releasing is in an manner which maintains the therapeutic level of lipoic acid for a period which is 10% or more longer as compared to a quick release formulation.  
     
     
         24 . The formulation of  claim 22  wherein the releasing is in a manner which maintains the therapeutic level of lipoic acid for a period which is 50% or more longer as compared to a quick release formulation.  
     
     
         25 . The formulation of  claim 22 , wherein the releasing is in an manner which maintains the therapeutic level of lipoic acid for a period which is 100% or more longer as compared to a quick release formulation.  
     
     
         26 . The formulation of  claim 22 , wherein the releasing is in an manner which maintains the therapeutic level of lipoic acid for a period which is 200% or more longer as compared to a quick release formulation.  
     
     
         27 . The formulation of  claim 22 ,wherein the releasing is sufficiently slow that a maximum level of lipoic acid obtained is less as compared to a maximum level obtained with a quick release formulation.  
     
     
         28 . The formulation of  claim 21 , wherein the orally active antidiabetic is metformin hydrochloride.  
     
     
         29 . The formulation of  claim 22 , wherein the lipoic acid is present as a racemic mixture and the therapeutic level is maintained over a period of four hours or more.  
     
     
         30 . The formulation of  claim 22 , wherein the lipoic acid is present as substantially pure R-(+) enantiomer and the therapeutic level is maintained over a period of four hours or more.  
     
     
         31 . The formulation of  claim 22 , wherein the releasing of the lipoic acid is at a rate of about 25% or less per hour after an initial release rate within 30 minutes following administration as compared to a quick release formulation.  
     
     
         32 . The formulation of  claim 22 , wherein the releasing of the lipoic acid is at a rate of about 50% or less per hour after an initial release rate within 30 minutes following administration as compared to a quick release formulation.  
     
     
         33 . A method of treating a human patient, comprising: 
 administering to a human patient a controlled release formulation of an orally active antidiabetic chosen from a sulfonylurea, a biguanide and a thiazolidinedione, and lipoic acid.    
     
     
         34 . The method of  claim 33 , wherein the formulation is characterized by maintaining a therapeutic level of lipoic acid in the patient's circulatory system over a period of time greater than that obtained with a quick release formulation.  
     
     
         35 . The method of  claim 34 , further comprising: 
 repeating the administering on three or more consecutive days thereby maintain a therapeutic level of lipoic acid in the patient's circulatory system over a therapeutically effective period of time on three or more consecutive days.    
     
     
         36 . The method of  claim 34 , wherein the therapeutic level is maintained over a period of time which is 10% or more than that obtained with a quick release formulation and further wherein the repeating is over thirty or more consecutive days.  
     
     
         37 . The method of  claim 34 , wherein the therapeutic level is maintained over a period of time which is 100% or more than that obtained with a quick release formulation and further wherein the repeating is over thirty or more consecutive days.  
     
     
         38 . The method of  claim 34 , wherein the therapeutic level is a level sufficient to obtain measurable vasodilation in a human patient.  
     
     
         39 . The method of  claim 34 , wherein the therapeutic level is a level sufficient to obtain a measurable reduction in a human patient's serum glucose level.  
     
     
         40 . A method of reducing a human patient's serum glucose level, comprising: 
 administering a therapeutically effective amount of an orally active antidiabetic selected from the group consisting of a sulfonylurea, a biguanide and a thiazolidinedione; and    administering an oral controlled release formulation of lipoic acid.    
     
     
         41 . The method of  claim 40 , further comprising: 
 repeatedly administering the antidiabetic and the lipoic acid on a daily basis for three or more days.    
     
     
         42 . The method of  claim 41 , wherein the antidiabetic is metformin hydrochloride which is administered in an amount in a range of about 500 mg to about 1,000 mg per day.