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EP-3519812-B1 - ALA AND SALT FORMULATION

EP3519812B1EP 3519812 B1EP3519812 B1EP 3519812B1EP-3519812-B1

Inventors

  • BENJAMIN, Jeffery, Lee
  • ZOLENTROFF, William, C

Dates

Publication Date
20260506
Application Date
20170927

Claims (15)

  1. An orally dissolvable tablet comprising (a) non-polymerized alpha-lipoic acid in a weight concentration of 12%-45% and (b) a physiologically acceptable salt in a weight concentration such that the weight concentration ratio of the salt to the alpha-lipoic acid in the tablet is in the range between 5% and 200%, and wherein the tablet upon administration is suitable for being maintained in a recipient's mouth until fully dissolved.
  2. The orally dissolvable tablet of claim 1, wherein the salt is an inorganic salt.
  3. The orally dissolvable tablet of claim 2, wherein the salt comprises a sodium cation.
  4. The orally dissolvable tablet of claim 3, wherein the salt is sodium chloride.
  5. The orally dissolvable tablet of claim 3, wherein the tablet further comprises a sugar that increases the bioavailability of the alpha-lipoic acid.
  6. The orally dissolvable tablet of claim 5, wherein the sugar is selected from the list consisting of sucrose, dextrose, fructose, and maltose.
  7. An orally dissolvable tablet comprising a non-polymerized alpha-lipoic acid molecule comprising a hydrogen substitution with a cationic atom or group in a weight concentration of 12%-45%.
  8. The orally dissolvable tablet of claim 7, wherein the cationic atom or group is sodium chloride.
  9. The orally dissolvable tablet of claim 8, wherein the tablet further comprises a sugar that increases the bioavailability of the alpha-lipoic acid.
  10. The orally dissolvable tablet of claim 9, wherein the sugar is selected from the list consisting of sucrose, dextrose, fructose, and maltose.
  11. An orally administered and orally dissolving formulation comprising alpha-lipoic acid and a salt comprising a cation and anion, wherein the formulation upon administration is suitable for being maintained in a recipient's mouth until fully dissolved.
  12. The orally administered and orally dissolving formulation of claim 11, wherein the formulation is a compressed tablet, the alpha-lipoic acid is non-polymerized, the weight concentration of the alpha-lipoic acid in the formulation is in the range 12% to 45% and the salt-to-alpha lipoic acid weight concentration is in the range 5% to 200%.
  13. The orally dissolvable tablet or orally dissolving formulation according to any one of the preceding claims, for use in a method of therapy wherein the tablet or formulation is maintained in the recipient's mouth until fully dissolved.
  14. The orally dissolvable tablet or orally dissolving formulation according to any one of claims 1 to 12 for use in treatment of pain associated with diabetic neuropathy.
  15. The orally dissolvable tablet for the use according to claim 14, wherein most subjects receiving the tablet find dissolving the tablet completely in the mouth to be adequate, satisfactory, or agreeable for daily use.

Description

BACKGROUND OF THE INVENTION Alpha lipoic acid or ALA has two chiral enantiomers. It is found as R-(+)-lipoic acid (RLA) and S-(-)-lipoic acid (SLA), and quite commonly, ALA is found as a racemic mixture of the two R/S-Lipoic acids. Additionally, each of these thioctic acid enantiomers exist in reduced (dihydro-lipoic acid) and oxidized forms. The disclosures herein are generally effective for any and/or all of the above ALA variants. The term thioctic acid, alpha lipoic acid, or ALA refers to all of these various species of lipoic acid, unless specifically referred to otherwise. ALA is commonly used as a health supplement and also is helpful in treating a variety of diseases, particularly those involving blood sugar problems such as type II diabetes and diabetic neuropathy. The IV delivery of ALA has proven to be more effective than the ingested supplement, particularly for diabetic neuropathy. However, on an ongoing basis, particularly weekly or daily is impractical. US 9,265,753 and US 15/050,462, published as US 2016-0235709 A1, have disclosed that a lozenge or tablet that dissolves in the mouth releasing ALA can provide ALA to the bloodstream in quantities more similar to IV than the supplements. The problem is the releasing too much ALA at any given time will oral irritation and burning. To solve this US 9,265,753 and US 15/050,462 provide for a slow steady dissolution of the formulation and appropriate, fairly low, concentrations of ALA. The limitation to this solution is that it can take longer than desired to get a large dose of ALA, for example 600 mg. US 2007/0196442 A1 describes a method for improving the oral administration of alpha-lipoic acid. BRIEF SUMMARY OF THE INVENTION The present invention provides an orally dissolvable tablet comprising (a) alpha-lipoic acid in a weight concentration of 12%-45% and (b) a physiologically acceptable salt in a weight concentration such that the weight concentration ratio of the salt to the alpha-lipoic acid in the tablet is in the range between 5% and 200%, and wherein the tablet upon administration is suitable for being maintained in a recipient's mouth until fully dissolved. In one embodiment, the salt is an inorganic salt, preferably the salt comprises a sodium cation, more preferably the salt is sodium chloride. In one embodiment, the tablet further comprises a sugar that increases the bioavailability of the alpha-lipoic acid, preferably the sugar is selected from the list consisting of sucrose, dextrose, fructose, and maltose. The present invention also provides an orally dissolvable tablet comprising an alpha-lipoic acid molecule comprising a hydrogen substitution with a cationic atom or group in a weight concentration of 12%-45%. In one embodiment, the cationic atom or group is sodium chloride. In a preferred embodiment, the tablet further comprises a sugar that increases the bioavailability of the alpha-lipoic acid, preferably the sugar is selected from the list consisting of sucrose, dextrose, fructose, and maltose. The present invention also provides an orally administered and orally dissolving formulation comprising alpha-lipoic acid and a salt comprising a cation and anion, wherein the formulation upon administration is suitable for being maintained in a recipient's mouth until fully dissolved. In one embodiment, the formulation is a compressed tablet, the alpha-lipoic acid is non-polymerized, the weight concentration of the alpha-lipoic acid in the formulation is in the range 12% to 45% and the salt-to-alpha lipoic acid weight concentration is in the range 5% to 200%. The present invention also provides the orally dissolvable tablet or orally dissolving formulation according to the present invention for use in a method of therapy, wherein the tablet or formulation is maintained in the recipient's mouth until fully dissolved. The present invention also provides the orally dissolvable tablet or orally dissolving formulation according to the present invention for use in treatment of pain associated with diabetic neuropathy. In one embodiment, most subjects receiving the tablet find dissolving the tablet completely in the mouth to be adequate, satisfactory, or agreeable for daily use. The addition of a salt to an ALA formulation reduces the degree of burning or irritation from ALA exposure during administration. This is particularly useful for an oral dissolve form of administration due to the extended time of ALA exposure. This salt-inclusive formulation either increases the efficacy of the ALA administration, reduces negative side effects, or both. This occurs because the formulation can have higher concentrations of ALA or faster dissolution times than a formulation without NaCl. In turn this allows larger amounts of ALA to be released more rapidly, which means larger amounts of ALA enter the bloodstream more rapidly without causing undue irritation. This can also reduce the time required to take the formulation and/or reduce the size (or numbe