Oral formulation of lipid soluble thiamine, lipoic acid, creatine derivative, and L-arginine alpha-ketoglutarate
A formulation comprised of four active components which are a lipid soluble thiamine, lipoic acid, arginine α-ketoglutarate, and a creatine derivative for oral administration is disclosed. The active components may be combined with excipient materials in such a way that those materials provide for an immediate release of a first portion of the active ingredients from the formulation following by a gradual release of any remaining active ingredients in a manner which makes it possible to (1) quickly obtain a therapeutic level of the active ingredients; and (2) substantially increase the period of time over which therapeutic levels of the active ingredients are maintained relative to a quick release formulation. These features make it possible to use the formulation to obtain a range of beneficial effects including reducing serum glucose levels and maintaining those reduced glucose levels over time to treat diabetic polyneuropathy as well as improving circulation and increasing muscle performance.
1 . An oral dosage formulation, comprising:
an excipient material and any two or more of active components chosen from:
a therapeutically effective amount of arginine α-ketoglutarate;
a therapeutically effective amount of a creatine derivative;
a therapeutically effective amount of lipoic acid; and
a therapeutically effective amount of a lipid soluble thiamine.
2 . The formulation of claim 1 , wherein the lipoic acid comprises a racemic mixture of enantiomers.
3 . The formulation of claim 1 , wherein the creatine derivative is a creatine ester.
4 . The formulation of claim 3 , wherein the creatine ester is creatine ethyl ester.
5 . The formulation of claim 1 , wherein the formulation is characterized by releasing a first portion of the lipoic acid sufficient to obtain a therapeutic level at a first rate substantially equivalent to a release rate of a quick release formulation and releasing a remaining portion of the lipoic acid at a controlled rate which is below a release rate of a quick release formulation.
6 . The formulation of claim 5 , wherein the first portion of the lipoic acid is from about 10% to about 50% of the lipoic acid in the formulation.
7 . The formulation of claim 1 , wherein the formulation comprises any three of the active components.
8 . The formulation of claim 1 , wherein the formulation comprises all four of the active components.
9 . The formulation of claim 1 , wherein the lipid soluble thiamine is chosen from benfotiamine and prosultamine.
10 . The formulation of claim 8 , further comprising an orally active antidiabetic chosen from a sulfonylurea, a biguanide and a thiazolidinedione.
11 . The formulation of claim 8 , further comprising metformin hydrochloride.
12 . The formulation of claim 1 , wherein the lipoic acid is present as a racemic mixture of R-(+) and S-(−) enantiomers and the therapeutic level is maintained over a period of four hours or more.
13 . The formulation of claim 1 , 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 and further wherein the lipid soluble thiamine is chosen from benfotiamine and prosultamine.
14 . A method of treatment, comprising:
orally administering to a patient a formulation comprising two or more active components chosen from a lipid soluble thiamine, lipoic acid, arginine α-ketoglutarate and a creatine derivative; and
repeating the administering on three or more consecutive days thereby maintain a therapeutic level of active components in the patient's circulatory system over a therapeutically effective period of time on three or more consecutive days.
15 . The method of claim 14 , 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.
16 . The method of claim 14 , 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.
17 . The method of claim 16 , wherein one of the active components is lipoic acid and the therapeutic level of lipoic acid is a level sufficient to obtain measurable vasodilation in a human patient.
18 . The method of claim 17 , wherein the therapeutic level is a level sufficient to obtain a measurable reduction in a human patient's serum glucose level of 10% or more compared to a level prior to administering the formulation.
19 . The method of claim 14 , further comprising:
repeatedly administering the formulation on a daily basis for five or more days.
20 . A method of treating a human patient, comprising:
administering to a human patient a formulation comprising active components of a lipid soluble thiamine, lipoic acid, arginine α-ketoglutarate, and a creatine derivative which formulation is characterized by maintaining a therapeutic level of the active components in the patient's circulatory system over a therapeutically effective period of time; and
repeating the administering on three or more consecutive days thereby maintaining a therapeutic level of the active components in the patient's circulatory system over a therapeutically effective period of time on three or more consecutive days.