SK15442000A3 - Composition comprising l-carnitine or an alkanoyl l-carnitine and nadh and/or nadph - Google Patents

Abstract

A composition is disclosed which comprises L-carnitine or an alkanoyl L-carnitine or the pharmacologically acceptable salt thereof and NADH and/or NADPH, useful as a dietary supplement for individuals engaging in strenuous physical exercise or asthenic subjects and, as a medicament, for treating the chronic fatigue syndrome and Parkinson's disease.

Description

Technical field

The present invention relates to a composition that has an effect on metabolism as well as on the performance of skeletal muscle energy and on regulation of muscle movement and coordination at the central level by enhancing effects at the level of both peripheral muscles and the central nervous system. Accordingly, the composition may take form and act as a dietary supplement or topical drug depending on the supportive or preventive action, or explicitly therapeutic action, wherein the composition is utilized in relation to the individual to whom it is administered.

BACKGROUND OF THE INVENTION

Especially as a dietary supplement or preventive agent, the composition of the invention is particularly suitable for facilitating the adaptation of skeletal muscles of individuals contributing to intense, long-term physical activity and alleviating muscle fatigue and exhaustion in asthenic persons, even in the total absence of any form of more or less intense physical activity.

Anyone who carries out sports activities, whether professionally or as an amateur, wishes to achieve and then maintain as much as possible a degree of skeletal muscle adaptation to cope with intense physical activity for as long as possible. Finding this optimal condition may lead to inappropriate use of drugs, especially steroids. It is well known that such drugs can enhance protein synthesis and consequently promote muscle growth to a greater extent than can be achieved by training or diet. However, the use of these drugs is illegal and undoubtedly harmful when practiced in professional sports.

Clearly, the only way to achieve the above goal is to properly complete the appropriate training program associated with the respective diets, multiplied by delivering the appropriate dietary supplements.

As used herein, the term "asthenia" refers to a diffuse group of non-specific syndromes typical of stressful living conditions usually prevalent in most urban and suburban areas and built-up areas, and encompassing large numbers of people, regardless of age and social-related factors characterized by deficiency or loss. muscle strength with slight fatigue and inadequate reaction to irritation.

When expressly used as a therapeutic agent, one important application of the composition of the invention is the treatment of chronic fatigue syndrome and Parkinson's disease and idiopathic parkinsonism-like syndrome caused by the administration of illicit drugs.

Chronic Exhaustion Syndrome (CFS), officially described for the first time in 1988 in the Annals of Internal Medicine, is a disease characterized by a degree of fatigue not explained by any other cause, often much more intense than it occurs in very serious diseases such as tumors and AIDS, and to such an extent that it causes more than a 50% reduction in work activity and normal social relationships for more than 6 months.

According to the criterion outlined in the Annals of Internal Medicine (December 1994) for diagnosing chronic fatigue syndrome, at least four of the following eight symptoms must be present in the patient for a period of 6 months:

1. neuropsychological disorders such as memory loss, excessive irritability, mental confusion, difficulty in thinking and concentration;

2. Pharyngitis;

3. palpable painful cervical or axillary lymph nodes;

4. muscle pain;

5. Migraine joint pain but without any swelling of the joints;

6. general headache of different types, characteristic and severe pain for each headache in the patient prior to the disease;

7. sleep disorders characterized by insomnia or hypersomnia;

8. total fatigue and malaise lasting 24 hours or more after physical activity at a level that was previously easily tolerated.

It is well known that Parkinson's disease is generally considered to be an idiopathic condition, and the symptoms of parkinsonism may be based on excessive uptake of drugs such as phenothiazine. butyrophenones and reserpine. Recently, Parkinsonism has been investigated in the overexpression of drugs by injecting them with meperidine-like compounds, an increased synthesis of which was produced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenyl-propoxy- piperidine (MPPP).

In fact, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP or NMPTP) and 1-methyl-4-phenyl-propoxy-piperidine (MPPP) selectively destroy dopaminergic neurons in the nigra subtantia and induce human and non-human primates, which may be completely similar to idiopathic Parkinson's disease with respect to its clinical, pathological and biochemical aspects, and its pharmacological responses.

The similarity between idiopathic Parkinson's disease and MPTP-induced parkinsonism is so great that it has been determined as a postulate (Burns et al .: The neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the monkey and man Can. J. Neur. Sci., 1J., N.1 (supplement), 166-168, February 1984), so that this parkinsonism "could produce more than a model." MPTP-induced parkinsonism suggests an apparent toxic cause in Parkinson's disease. ”

The choice of therapy for managing Parkinson's disease is commonly based on the administration of levo-dopa (L-dopa), a metabolic precursor of dopamine that itself is unable to cross the blood barriers in the brain.

Since levo-dopa is extensively metabolised before being able to reach sites of action in the brain, it should be administered at very high doses. Thus, L-dopa is co-administered with cardidopa, an inhibitor of dopecarboxylase, which prevents systemic metabolism of levodopa before the latter reaches the brain.

When levodopa is administered alone, side effects such as e.g. anorexia, nausea and vomiting or orthostatic hypotension, which are, however, significantly less severe when carbidopa is also administered.

However, after several months of L-dopa therapy, the dyskinetic movements of the face, torso and limbs are possible and frequent, even when co-administered with a decarboxylation inhibitor. The onset of such movements indicates in most cases that the dose of the drug has reached a critical value which must not be exceeded.

Then, there is a strong need for a support / preventive / therapeutic agent which, as a result of its efficacy, substantial non-toxicity and loss of side effects, can be safely used by such a wide range of users in cases where an appropriate dietary supplement is simply needed. pathological conditions.

SUMMARY OF THE INVENTION

These multiple objectives - the creation of a supportive, preventive and explicitly therapeutic agent - are achieved by a composition according to the invention which consists, as will be described in more detail below, of a novel combination comprising L-carnitine or lower C2-C6 alkanoyl L-carnitine as its constituent; their pharmacologically acceptable salts and nicotinamide adenine dinucleotide (NADH) or a precursor of NADH and / or nicotinamide adenine dinucleotide phosphate, reduced form (NADPH).

Many decades have passed since the basic discovery (Fritz IB: The metabolic consequences of carnitine effects on long-chain fatty acid oxidation. Ed. FC Gran, New York, Academic Press, 1968, pp. 39-63) that L-carnitine it is specific in playing a vital physiological role as a long-chain fatty acid carrier across the inner mitochondrial membrane into the mitochondrial matrix that is the site of their oxidation and since the primary L-carnitine deficiency was first identified (Engel and Angelini, Science, 1973, 179: 899 -902) as the cause of some, sometimes fatal, albeit extraordinary form of myopathy (lipid deposition myopathy), has been a huge advance in our understanding of the pathological consequences of primary and secondary L-carnitine deficiency, and vice versa, the therapeutic and nutritional value of exogenous L- carnitine.

Carnitine is present in all biological tissues at relatively high concentrations as free carnitine and lower concentrations in the form of acylcarnitines, which are metabolic products of the reversible reaction.

acyl CoA + carnitine acylcarnitine + CoASH catalyzed by three groups of enzymes, i. transferases, which differ from each other according to their specificity for the reaction substrates: a carnitine acetyl transferase (CAT) group whose substrate is short-chain acyl groups (such as acetyl and propionyl); a carnitine octanoyl transferase (COT) group whose substrate comprises medium chain acyl groups; and a carnitine palmitoyl transferase (CPT) group whose substrate comprises long-chain acyl groups.

The important role of carnitine in auxiliary metabolism, with a significant reference to its limited biosynthesis, serves to explain how carnitine deficiency can occur as a secondary case in various pathological functions involving different organs and systems. The widening of the clinical spectrum is reflected in an increase in the number of therapeutic options for the deficiency of this natural compound; the full extent and impact of the deficiency was revealed when it was observed that L-carnitine replacement therapy dramatically reversed the clinical picture in patients suffering from lipid deposition myopathy. The Food and Drug Administration (FDA) disagrees not only with the inclusion of L-carnitine as a "solitary drug", but also includes it in the list of "life-saving" drugs.

Advancing our knowledge of the pathological consequences of primary and secondary L-carnitine deficiency has been accompanied by a very substantial increase in scientific and patent publications mainly focused on L-carnitine and to a much lesser extent on some acylcarnitines.

Pursuant to a partial investigation of the patent situation, the use of L-carnitine in the cardiovascular area for the treatment of cardiac arrhythmias and insufficient cardiac perfusion (US 4,656,191), ischemic heart disease and cardiac anoxia has been suggested (US 4,649,159); in the field of lipid metabolism disorders for the treatment of hyperlipidemia and hyperlipoproteinemia (US 4,315,944) and for the normalization of non-normal HDL: LDL: VLDL ratios (US 4,255,449); in the field of total parenteral nutrition (US 4,254,147 and US 4,320,145); in nephrology against myasthenia and at the onset of muscle cramps due to carnitine loss in dialysis in chronic uraemia patients undergoing regular hemodialysis treatment (US 4,272,549); against toxic effects induced by anticancer agents such as adriamycin (US 4 400 371 and US 4 713 370) and halogenated anesthetics such as halothane (US 4 780 308); for the treatment of venostasis (US 4,415,589); against worsening of a large number of biochemical and behavioral parameters in the elderly (US 4,474,812); for normalizing triglyceride factor and tumor necrosis factor (TNF-α) levels in AIDS patients and in asymptomatic HIV-positive patients.

It has also been suggested to use L-carnitine in combination with other active ingredients, such as the combination of L-carnitine with coenzyme Q10 with a broad spectrum of metabolic / antisclerotic activity (US 4,599,232).

With respect to alkanoyl L-carnitine, the use of acetyl L-carnitine is known in the treatment of diseases of the central nervous system, in particular Alzheimer's disease (US 4,346,107) and in the treatment of diabetic neuropathy (US 4,751,242), whereas

L-carnitine has been suggested for the treatment of peripheral vasculopathy (US 4,343,816) and cardiac insufficiency (US 4,194,006).

Equally part of the complex is the activity exhibited by nicotinamide adenine dinucletide coenzyme (NADH), whose role at energy level is well known.

Its function in the respiratory chain is essential for electron transfer in the mitochondrial system and in the ATP unit. Two NADH dehydrogenases were isolated from the internal mitochondrial matrix. One of them with a lower molecular weight (molecular weight 78,000), which is probably a subunit of a larger complex (molecular weight about 300,000), appears to be a naturally occurring functional form of this system.

The various complexes found in the inner mitochondrial membrane form a chain of oxidation systems that pass under the name cytochrome and coenzyme Q10 and allow electrons to be transferred from a lower potential system to a higher potential system using oxygen and an ATP unit. It is in fact from the respiratory chain that it is obtained from oxidative phosphorylation that leads from NADH to the formation of ATP.

NADH along with cytochrome Q10 coenzyme complexes are the elements necessary for energy transformation to ATP and NADH, which is considered the beginning of this chain for the major conditioning element in this process.

The enzymatic function of NADH is quite detectable in the energy type reaction in the ATP unit, but it has recently been shown that NADH acts as a coenzyme required for quinodihydroxy-pteridine reductase (DHPR) to undergo H4biopterin biosynthesis.

The possibility of stimulating H4-biopterin biosynthesis and increasing its brain concentration has recently been suggested as a method of increasing L-dopa and thus dopamine, whose deficiencies are found in diseases such as parkinsonism, these deficiencies being considered to cause parkinsonism neuropathy. If L-dopa can act as a precursor of dopamine and then metabolically transforms into the latter, the same will not be the case for tyrosine, which may also be considered as a precursor capable of producing L-dopa in the absence of tyrosine hydroxylase. In fact, a reduction in this enzyme was found in people suffering from parkinsonism at the nigra subtance level. In addition, the reduction in hydroxytyrosine could be accompanied by a strong reduction in H4-biopterin, a consensus required for the synthesis of hydroxytyrosine. Since H4-biopterin does not cross the blood barriers in the brain and therefore direct administration of H4-biopterin is not possible, it seems to be useful to use stimulation of H4-biopterin formation by administering the coenzyme required for quinodihydroxy-pteridine reductase (DHPR) activity. it is known to be performed by NADH. Thus, administration of NADH activates DHPR leading to the generation of H4-biopterin required in turn to activate tyrosine hydroxylase to achieve dopamine novosynthesis.

Clinical trials based on intravenous administration of NADH to individuals suffering from Parkinson's disease confirm the validity of theoretical assumptions with

outlined above, showing a marked improvement in the symptoms of Parkinson's disease in subjects so treated.

Extensive comparable results were obtained with oral administration of NADH, in which gastrointestinal capsules were released over a prolonged period to avoid the acidic environment of the stomach, which may lead to rapid reduction in NADH levels.

Clinical improvements in Alzheimer's disease and chronic fatigue syndrome (CFS) have also been reported with administration of NADH (Birkmayer J.G., Annals Clin. Lb. Sci., 26, 1, 1996).

Based on the properties of the compounds described above, the possibility of interaction between them was determined by means of a series of tests performed on combinations of Lcarnitine or its alkanoyl derivatives and NADH and / or NADPH. By means of these tests performed on these new combinations, surprisingly unexpected synergistic interactions have been observed between the components of the combinations which are absolutely unpredictable based on our pharmacological knowledge of L-carnitine or its alkanoyl derivatives and NADH and NADPH.

The composition of the invention comprises the following components in combination:

a) L-carnitine or alkanoyl L-carnitine in which the straight or branched chain alkanoyl group has 2-8 carbon atoms, and preferably 2-6 carbon atoms, or one of its pharmacologically acceptable salts;

b) NADH or a precursor of NADH and / or NADPH; and

c) a pharmacologically acceptable excipient.

Preferably, the NADH precursor is nicotinamide.

The weight ratio of a) to b) is generally in the range of 1: 0.01 to 1: 1, and more preferably it should be from 1: 0.05 to 1: 0.5, for example, the weight ratio may be 1: 0.1 .

The alkanoyl L-carnitine should preferably be selected from the group consisting of acetyl L-carnitine, propionyl L-carnitine, butyryl L-carnitine, valeryl L-carnitine and isovaleryl Larmarmine. Acetyl L-carnitine and propionyl L-carnitine are highly preferred.

For the purposes of this invention, it is understood that L-carnitine, acetyl L-carnitine, propionyl L-carnitine and isovaleryl L-carnitine in these compounds are in the form of inner salts.

Pharmacologically acceptable salts of L-carnitine or alkanoyl L-carnitine are any acid salts thereof that do not give rise to undesirable toxic or side effects. These acids are well known to pharmacologists and pharmacists.

Non-limiting examples of such salts are: choride, bromide, iodide, aspartate, aspartic acid, citrate, citric acid, tartrate, phosphate, phosphoric acid, fumarate, fumaric acid, glycerophosphate, glucose phosphate, lactate, maleate, maleic acid, orotate, oxalate, oxalic acid, sulfuric acid, trichloroacetate, trifluoroacetate and methanesulfonate.

A list of FDA approved pharmacologically acceptable salts has been reported in Int. J. Pharm. 33, (1986), 201-217, which is incorporated herein by reference.

The composition of the invention may further comprise vitamins, coenzymes, minerals and antioxidants.

The composition of the invention in unit dosage form contains, for example, 100-500 mg of a) L-carnitine or alkanoyl L-carnitine or an equivalent amount of one of their pharmacologically acceptable salts and a weight amount of b) NADH or NADPH such that weight ratio a): b) it is in the range from 1: 0.01 to 1.Ί, and preferably from 1: 0.02 to 1: 0.2.

For the sake of simplicity, only the combination of L-carnitine and NADH will be referred to hereinafter, but it is to be understood that the combination of L-carnitine and NADPH or the abovementioned

ΙΟ alkanoyl L-carnitines and NADH and / or NADPH are equally effective, fully achieving the objectives of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

Toxicological tests

Carnitine and NADH are known to have only limited toxicity and good tolerance. These favorable properties were confirmed by intravenous administration of the combination to 100 mg / kg of L-carnitine and 5 mg / kg of NADH to rats and mice. In long-term toxicity tests, a combination of 250 mg / kg L-carnitine and 10 mg NADH was well tolerated and was not the cause of either mortality or toxicity or intolerance in the treated animals. Blood tests and histological examinations of various organs at the end of treatment revealed no abnormalities compared to control animals, confirming the good tolerance of the combination studied.

Tests to increase muscle enzymes after long-term exercise

To determine the effect of carnitine and NADH as well as the combination of these two on muscle performance concentration of mitochondrial enzymes, tests were performed to determine whether the activity of these mitochondrial enzymes in the gastrocnome muscle of rats undergoing long-term muscle performance could be increased compared to control animals due to larger energy requirements necessary for long-term muscular effort. At the end, a group of Wistar rats were subjected to muscle exercise by placing them in a Rotaroid apparatus (Basile, Como, Italy) at a speed of 20 m / min for 120 minutes per day (Benzi G., J. Appl. Physiol., 38, 565, 1975). . Muscle enzyme activity was determined after seven or thirty days of exercise, gastrocnome muscle was isolated and homogenized in each rat (Oscai L.B., J. Biol. Med., 245, 6968, 1971). The enzymes determined were citrate synthetase, isocitrate dehydrogenase and succinate dehydrogenase.

The results obtained in these tests showed that the combination of carnitine and NADH was able to induce a very significant increase in enzyme activity after only seven days of exercise, whereas in this observation no changes induced by either carnitine or NADH alone were found compared to control muscles.

II

Strong synergistic effect thirty days of exercise: these two products was perhaps more obvious treatment Number of days citrate isocitrate succinate exercises synthetase dehydrogenase dehydrogenase inspection 0 20.9 ± 1.4 2.25 ± 0.31 3.70 ± 0.22 inspection 7 22.1 ± 1.6 2.30 ± 0.20 3.90 ± 0.19 inspection 30 29.9 ± 2.1 3.33 ± 0.20 5.20 ± 0.30 Carmtine 250 mg / kg 0 20.8 ± 0.95 3.05 ± 0.19 3.35 ± 0.35 Carnitine 250 mg / kg 7 22.6 ± 1.9 2.85 ± 0.31 3.85 ± 0.45 Camitin 250 mg / kg 30 30.1 ± 0.95 2.98 ± 0.16 4.90 ± 0.33 NADH 10 mg / kg 0 21.5 ± 1.4 2.35 ± 0.29 3.60 ± 0.21 NADH 10 mg / kg 7 30.5 ± 2.5 3.65 ± 0.55 4.15 ± 0.45 NADH 10 mg / kg 30 33.6 ± 2.1 3.55 ± 0.36 5.40 ± 0.45 Carnitine 250 mg / kg + NADH 10 mg / kg 0 21.4 ± 1.9 2.15 ± 0.18 3.80 ± 0.22 Carnitine 250 mg / kg + NADH 10 mg / kg 7 47.7 ± 3.92 5.1 ± 0.29 7.15 ± 0.30 Carnitine 250 mg / kg + NADH 10 mg / kg 30 75.9 ± 3.51 6.3 ± 0.5 9.25 ± 0.65

(*) Enzymatic activity is expressed as pmol of substrate used per min / g of tissue weight

Assays for Increasing ATP Concentrations After Hypoxia in Rabbit Papillary Muscles These tests were used to determine whether L-carnitine and NADH, or a combination thereof, is capable of maintaining ATP concentrations in the papillary muscle of the rabbit heart after exposure to rabbits known to result in hypoxia. draining this energy compound. The tests were performed in New Zealand rabbits receiving both intravenous injections of L-carnitine (100 mg / kg) and NADH (10 mg / kg) administered alone, as well as combinations of the two agents daily for three consecutive days.

Another group consisted of a control group receiving no treatment. At the end of the third day of treatment, all animals were sacrificed, their hearts were extracted, and portions of the papillary muscle that were 1 mm in diameter and 4.5 mm thick were isolated. The tissues thus isolated were washed in a thermostatic bath with 100% saturated oxygen solution. Experimental hypoxia was then created by introducing 100% nitrogen into the bath instead of oxygen. The ATP content of the papillary muscle was analyzed using the method described by Strehler B.L. (Strehler B. L., Methods in Enzymology III, New York Acad. Press, 871, 1957). The analysis was performed on tissue samples maintained under normal washing for 90 minutes and after a period of hypoxia also lasting 90 minutes.

These tests showed that ATP concentrations differed significantly in control animals and in animals treated with either carnitine or NADH alone. On the other hand, animals treated with a combination of carnitine and NADH were found to fully protect against the reduction of ATP induced by hypoxia.

These tests then revealed the ability of the combination of L-carnitine and NADH to protect the ATP present in the papillary muscle against reduction induced by hypoxia to an extent that could not be achieved by single L-carnitine or single NADH, but which surprisingly can be achieved by their combination.

ATP concentration (mol / g tissue)

treatment Before hypoxia After hypoxia inspection 1.54 ± 0.31 0.40 ± 0.051 Carnitine 100 mg / kg 1.65 ± 0.26 0.55 ± 0.031 NADH 10 mg / kg 1.60 ± 0.30 0.65 ± 0.044 Carnitine 100 mg / kg + NADH 10 mg / kg 1.90 ± 0.37 1.52 ± 0.061

Assays for the ability of L-carnitine and NADH to stimulate dopamine production

These assays were performed on neuroblastoma cell cultures with a cell concentration ranging from 15-30 to 60 million, with 200 µg NADH / ml or 2 mg / ml L-carnitine, or a combination of the two.

NADH and L-carnitine induced dopamine formation was analyzed by HPLC according to the Mayer method (Mayer GS, Strong RF, Current separation 4, 44, 1982) modified by Jonsson and Keller (Jonsson G., Holman H., Adams RN, Central Adrenaline Neurones. De Fuxe Pergamon Press, 59, 1980; Keller, R., Oke, A., Mefford, L., Life Sciences, 19, 995 (1976). The results of these assays show that the addition of NADH to the cell culture effectively induces an increase in dopamine production relative to the number of cells present.

However, a significantly greater increase was obtained when single L-carnitine, which produces only a very subtle effect, is added to the NADH solution. The synergistic effect is then also considerable in these tests.

Percentage increase in dopamine synthesis in cultures of neuroblastoma cells incubated with NADH or carnitine as a function of the number of cells incubated (in millions)

Number of cells % Number of cells % Number of cells % treatment (Millions) increase (Millions) increase (Millions) increase NADH 100 pg / ml 15 4.5 30 31.5 60 45.5 NADH 200 pg / ml 15 11.8 30 40.6 60 55.6 Carnitine 1 pg / ml 15 - 30 2.1 60 5.6 Carnitine 2 pg / ml 15 - 30 3.3 60 6.6 NaDH 100 pg / ml + Carnitine 1 pg / ml 15 6.6 30 45.2 60 50.6 NADH 200 µg / ml + NADH 100 pg / ml 15 18.4 30 56.4 60 70.5

MTPT (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) test

The use of MTPT as a neurotoxin particularly active at the level of the neuroskeleton system may be a significant experimental model for the study of parkinsonism and its biochemical and clinical pathogenesis.

In both monkey and mouse, high doses of MPTP (40 mg / kg) induce hypokinetic and bradykinetic symptoms typical of Parkinson's disease accompanied by an increasing reduction in dopa and its metabolites. In these assays, it was investigated whether MPTP-induced behavioral and mobility impairment in mice, as well as dopamine concentrations, could be modified and adjusted by administering NADH or L-carnitine administered alone or a combination of both.

C57 BE / 6 black mice weighing 20 g were used for these tests; one group of these mice was maintained as a control, while the other groups received two subcutaneous injections of 40 mg / kg MPTP at 24 hour intervals. Three weeks after the MPTP injection, the motility of all treated animals and control animals was evaluated. Dopa content analysis was also performed after three weeks of MPTP treatment. Treatment with NADH and carnitine was performed just before the start of the mobility test; mobility was analyzed using a plexiglass chamber through which two infrared rays were transversely passed at two different heights according to the procedure described by Archer (Archer T., Frederikson A., Psychopharmacology, 88, 141, 1986).

MTPT-induced motility reduction was greater than 80% in control mice, and motility with NADH and L-carnitine alone was reduced by about 60% and 70%, with the combination of these two being brought back to virtually normal levels (20% reduction). ). Also of interest were the dopa concentrations in the striated muscles, which were reduced by about 90% in MPTP-treated control mice, but were almost normal in the treated mice. Also in these assays, while the effect of self-administered L-carnitine was almost negligible and at NADH was equal to 40%, the combination reverted back to levels very close to those normally found in tissue.

Some examples of compositions of the invention are listed below:

1) L-carnitine inner salt 200 mg NADH 5 mg 2) L-carnitine inner salt 200 mg NADH 10 mg 3) Acetyl L-carnitine inner salt 250 mg NADH 5 mg 4) Acetyl L-carnitine inner salt 500 mg NADH 10 mg 5) Propionyl L-carnitine inner salt 250 mg NADH 5 mg 6) L-carnitine inner salt 200 mg NADH 5 mg Coenzyme Q10 20 mg pyridoxine 3 mg selenium 20 mg zinc 2 mg 7) L-carnitine inner salt 200 mg NADH 5 mg Coenzyme Q10 20 mg taurine 10 mg inosine 100 mg Creatine 100 mg Piruvic acid 10 mg

¾ / modified

Claims (12)

1. A composition comprising: (a) alkanoyl L-carnitine, wherein the alkanoyl group, straight or branched, has 2 to 8 carbon atoms, preferably 2 to 6 carbon atoms, or pharmacologically acceptable salts thereof; b) nicotinamide selected from the group consisting of nicotinamide, nicotinamide adenine dinucleotide, reduced shape (NADH) and nicotinamide adenine dinucleotide phosphate, reduced shape (NADPH); and c) a pharmacologically acceptable excipient. Composition according to claim 1, characterized in that the weight ratio (b) is from 1: 0.01 to 1: 1. The composition of claim 2, wherein the weight ratio of a): b) is from T 0.02 to 1: 0.2. The composition of claim 3, wherein the weight ratio a): b) is 1: 0.1. Composition according to claims 1 to 4, characterized in that the alkanoyl Lcarnitine is selected from the group comprising acetyl L-carnitine, propionyl L-carnitine, butyryl L-carnitine, valeryl L-carnitine and isovaleryl L-carnitine. Composition according to any one of the preceding claims, characterized in that the pharmacologically acceptable salts are selected from the group consisting of: chloride, bromide, iodide, aspartate, aspartic acid, citrate, citric acid, tartrate, phosphate, phosphoric acid, fumarate, fumaric acid, glycerophosphate, glucose phosphate, lactate, maleate, maleic acid, orotate, oxalate, oxalic acid, sulfuric acid, trichloroacetate, trifluoroacetate, and methanesulfonate. The composition of any preceding claim, further comprising vitamins, coenzymes, minerals, and antioxidants. The composition of claim 1, in unit dosage form comprising 100 500 mg of a) alkanoyl L-carnitine or an equivalent amount of its pharmacologically acceptable salts and an amount of b) nicotinamide adenine dinucleotide, precursor mcotinamide adenine dinucleotide or nicotinamide adenine dinucleotide phosphate such that the weight ratio a); b) is from 1: 0.01 to 1: 1. The composition of claim 3, in unit dosage form comprising 100 500 mg of a) alkanoyl L-carnitine or an equivalent amount of its pharmacologically acceptable salts and an amount of b) nicotinamide adenine dinucleotide, precursor nicotinamide adenine dinucleotide or nicotinamide adenine dinucleotide phosphate such that the weight ratio of a): b) is from 1: 0.02 to 1: 0.2. The composition of any preceding claim, administered orally and in the form of a dietary supplement. The composition of any preceding claim, administered orally or parenterally in the form of a medicament. 12. Use (a) L-carnitine or alkanoyl L-carnitine, in which the alkanoyl group, straight or branched, has 2 to 8 carbon atoms, preferably 2 to 6 carbon atoms, or pharmacologically acceptable salts thereof; b) nicotinamide selected from the group consisting of nicotinamide, nicotinamide adenine dinucleotide, reduced shape (NADH) and nicotinamide adenine dinucleotide phosphate, reduced shape (NADPH); and c) a pharmacologically acceptable excipient, for the preparation of a composition for the treatment of Parkinson's disease and illicit parkinsonism-inducing drugs.