Ala and salt formulation

Abstract

The addition of a salt to an ALA formulation that is dissolved in the mouth unexpectedly significantly reduces the degree of burning or irritation from ALA exposure during administration. This invention is particularly useful for an oral dissolved form of administration due to the extended time of ALA exposure that is possible with such formulations. The salt-inclusive formulations of the invention can increase efficacy of the ALA administration, reduce negative side effects, or both.

1 . A method of increasing the concentration of alpha-lipoic acid in the blood of a patient diagnosed as suffering from a disease or condition treatable by an increased bloodstream concentration of alpha-lipoic acid comprising lingually administering a dissolvable tablet comprising alpha-lipoic acid and a physiologically acceptable salt to the patient and instructing the patient to maintain the tablet in the patient's mouth until the tablet is fully dissolved, thereby causing the alpha-lipoic acid to be lingually absorbed and the concentration of alpha-lipoic acid in the patient's bloodstream to be increased to a level associated with treating the disease or condition and wherein the inclusion of the salt increases the number of patients that find the tablet tolerable for use. 
     
     
         2 . The method of  claim 1 , wherein the alpha-lipoic acid is the primary or only pharmaceutically active ingredient in the tablet known to have a therapeutic effect on the disease or condition. 
     
     
         3 . The method of  claim 2 , wherein the weight/weight ratio of the alpha-lipoic acid to the salt in the tablet is in the range of 20% to 100%. 
     
     
         4 . The method of  claim 3 , wherein the concentration of alpha-lipoic acid in the tablet is at least 30%. 
     
     
         5 . The method of  claim 4 , wherein the concentration of alpha lipoic acid in the tablet does not exceed 47.5%. 
     
     
         6 . The method of  claim 5 , the salt is formulated as a separate component from the alpha-lipoic acid in the tablet. 
     
     
         7 . The method of  claim 5 , wherein the tablet comprises a conjugate of the alpha-lipoic acid and the salt. 
     
     
         8 . The method of  claim 6 , wherein the salt comprises a sodium cation. 
     
     
         9 . The method of  claim 7 , wherein the salt comprises a sodium cation. 
     
     
         10 . The method of  claim 8 , wherein the salt is sodium chloride. 
     
     
         11 . The method of  claim 9 , wherein the salt is sodium chloride. 
     
     
         12 . The method of  claim 8 , wherein the alpha-lipoic acid comprises a mixture of both S- and R-alpha-lipoic acid (S-ALA and R-ALA) molecules. 
     
     
         13 . The method of  claim 12 , wherein the ratio of the concentration of S-ALA to the concentration of R-ALA in the tablet is not 1:1. 
     
     
         14 . The method of  claim 1 , wherein the alpha-lipoic acid comprises a mixture of both S- and R-alpha-lipoic acid (S-ALA and R-ALA) molecules. 
     
     
         15 . The method of  claim 14 , wherein the ratio of the concentration of S-ALA to the concentration of R-ALA in the tablet is not 1:1. 
     
     
         16 . The method of  claim 1 , wherein the alpha-lipoic acid comprises a single enantiomer of alpha lipoic acid. 
     
     
         17 . The method of  claim 8 , wherein the alpha-lipoic acid comprises a single enantiomer of alpha lipoic acid. 
     
     
         18 . The method of  claim 6 , wherein the tablet comprises an amount of a sugar in an amount that detectably enhances lingual absorption of the alpha-lipoic acid, detectably enhances uptake of the alpha-lipoic acid in the bloodstream, increases the number of patients that can tolerate dissolving the entire tablet in the mouth, or a combination of any or all thereof. 
     
     
         19 . The method of  claim 7 , wherein the tablet comprises an amount of a sugar in an amount that detectably enhances lingual absorption of the alpha-lipoic acid, detectably enhances uptake of the alpha-lipoic acid in the bloodstream, increases the number of patients that can tolerate dissolving the entire tablet in the mouth, or a combination of any or all thereof. 
     
     
         20 . The method of  claim 18 , wherein the sugar is a monosaccharide or a disaccharide. 
     
     
         21 . The method of  claim 20 , wherein the sugar comprises glucose. 
     
     
         22 . The method of  claim 19 , wherein the sugar is a monosaccharide or a disaccharide. 
     
     
         23 . The method of  claim 22 , wherein the sugar comprises glucose. 
     
     
         24 . The method of  claim 21 , wherein the tablet is formed by a method comprising compressing the alpha-lipoic acid and other tablet ingredients without heating the alpha-lipoic acid and the other compressed ingredients of the tablet to a temperature at which any of the other compressed ingredients of the tablet melt. 
     
     
         25 . The method of  claim 23 , wherein the tablet is formed by a method comprising compressing the alpha-lipoic acid and other tablet ingredients without heating the alpha-lipoic acid and the other compressed ingredients of the tablet to a temperature at which any of the other compressed ingredients of the tablet melt. 
     
     
         26 . The method of  claim 24 , wherein a majority of patients treated with the tablet find completely dissolving the tablet in the mouth to be tolerable. 
     
     
         27 . The method of  claim 25 , wherein a majority of patients treated with the tablet find completely dissolving the tablet in the mouth to be tolerable. 
     
     
         28 . The method of  claim 1 , wherein a majority of patients treated with the tablet find completely dissolving the tablet in the mouth to be tolerable. 
     
     
         29 . The method of  claim 26 , wherein the disease or condition comprises diabetic neuropathy. 
     
     
         30 . The method of  claim 27 , wherein the disease or condition comprises diabetic neuropathy. 
     
     
         31 . The method of  claim 1 , wherein the disease or condition comprises diabetic neuropathy. 
     
     
         32 . The method of  claim 29 , wherein alpha-lipoic acid is the only active pharmaceutical ingredient in the tablet. 
     
     
         33 . The method of  claim 30 , wherein alpha-lipoic acid is the only active pharmaceutical ingredient in the tablet. 
     
     
         34 . The method of  claim 31 , wherein alpha-lipoic acid is the only active pharmaceutical ingredient in the tablet. 
     
     
         35 . The method of  claim 1 , wherein the method comprises testing the patient's reaction to one or more tablets and determining an administration regimen for the patient comprising the concentration of one or more tablets and the frequency of administration of each tablet or tablets.