Basic alpha lipoic acid solution and its uses

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A solution is disclosed having a pH 7.0 to 9.5, comprising alpha lipoic acid or its enantiomer, an inorganic compound and a solvent, said solvent being a mixture of water and a polyol. Said solution presents high stability of the alpha lipoic acid over time, as well as high edibility and bioavailability.

The present invention concerns a solution having a pH 7.0 to 9.5, comprising alpha lipoic acid or its enantiomer, an inorganic compound selected from hydroxide, carbonate, bicarbonate and mixtures thereof, of sodium, potassium, calcium, magnesium, ammonium and mixtures thereof, and a solvent, said solvent being a mixture of water and a polyol selected from propylene glycol, glycerol, polyethylene glycol, polypropylene glycol, and mixtures thereof. Said solution presents high stability of the alpha lipoic acid over time, as well as high edibility and bioavailability.

From this reaction scheme it can be seen that the oxidising agent is the NAD+ and that the reaction produces an equivalent of NADH. The reaction takes place in the mitochondria and is essential for initiating Krebs cycle reactions.

The a-LA, previously in racemic form and, in more recent preparations, in enantiomeric form R, is widely used as a food supplement, and in some Countries, as a medicine for the treatment of diabetic polyneuropathy. The basis of the pharmacological action of a-lipoic acid are not yet entirely clear, although various hypotheses have been proposed in this regard. In particular, it has been hypothesised that in neuropathic processes, a-lipoic acid has a protective action due to its redox properties that are capable of neutralising, at least in part, the damage caused by the free radicals that are generated in the peripheral nervous system of the diabetic patient.

The antioxidant action of α-lipoic acid is also in part due to its ability to restore the endogenous levels of glutathione, the values of which are drastically reduced in neuropathic patients as a result of the reduction processes of excess glucose to sorbitol and of the latter's successive reoxidation to fructose. A large number of free radicals are generated in both . these reactions and it has recently been demonstrated that in the diabetic patient, these free radicals generated by the redox reactions involving glucose, lead to destruction of the nitric oxide (NO), a known vasodilator, therefore responsible for a correct supply to the peripheral nerves. A dramatic decrease of NO results into a vasoconstriction and, consequently, into an insufficient supply to the nerve tissue. It is therefore possible that this is the main cause of the damage that the excess glucose causes in the peripheral nerves of the diabetic patient. Furthermore, even the non-enzymatic glycation of a number of proteins, caused by the excess glucose, by determining a loss of protein functions, contributes to the neuropathic damage (Packer L et al., "Molecular aspects of lipoic acid in the prevention of diabetes complications", Nutrition, 2001 ; 17:888-895).

The literature (Amenta et al.; "Pharmacokinetics of different formulations of tioctic (alpha lipoic) acid in healthy volunteers", Clinical and Experimental Hypertension, 2008 30:767-775) confirms that pharmacokinetic studies have been carried out on humans, with the administration of lipoic acid by oral route at the doses normally used in food supplements and in pharmacological preparations (600 mg). Extremely variable values have been reported, particularly depending on the type of formulation used, however an extremely reduced bioavailability (less than 30%) was always observed. Some solid, delayed release forms were also prepared, however none of them significantly increased bioavailability and the time the lipoic acid lasts in the plasma.

The easiness with which alpha lipoic acid is metabolised by oxidation (particularly beta-oxidation) has been believed so far to be the main cause of its unfavourable pharmacokinetic characteristics. The R-enantiomer of a-LA, which is less toxic and is pharmacologically more active than the corresponding raceme, however presents the same unfavourable, pharmacokinetic characteristics as racemic a-LA. It is therefore the object of this invention to find a way to stabilise the alpha lipoic acid in solution so as to optimise the bioavailability and increase its preservation over time.