WO2006015774A1 - Physiologically acceptable composition containing alpha-lipoic acid, creatine, and a phosphatide - Google Patents

Abstract

Disclosed is a novel physiologically acceptable composition substantially containing a-lipoic acid, creatine and a phosphatide and/or one of the suitable derivatives thereof. Said composition preferably contains 0.01 to 80 percent by weight of the lipoic acid component, 1.0 to 99.9 percent of the creatine component, and 0.01 to 80 percent by weight of the phosphatide component and is used mainly for slowing down degenerative and particularly progressive modifications of the brain. Forms of administration such as food supplements, food, beverages, medicaments, cosmetics are particularly suitable. In general, the disclosed composition is used in individual doses ranging between 10 mg and 10 g. The inventive combination makes it possible to obtain results which additively exceed the effects of the individual compounds while representing cases of application that were unknown for the individual compounds.

Description

 Physiologically acceptable composition containing alpha lipoic acid, creatine and a phospholipid

description

The present invention describes a novel physiologically acceptable composition and its use.

α-lipoic acid (thioctic acid, l, 2-dithiolane-3-pentanoic acid) has been known for about 50 years as a growth factor from microorganisms; however, it also occurs as an R - (+) - enantiomer in low concentrations in higher plants and animals. Alpha-lipoic acid acts physiologically in hydrophilic and lipophilic media as coenzyme of the oxidative decarboxylation of α-ketocarboxylic acids (eg pyruvate, α-ketoglutarate). In addition, α-lipoic acid is also involved in the degradation of certain amino acids as a cofactor. In addition, it contributes to the regeneration of vitamin C, vitamin E, glutathione and coenzyme QlO. α-lipoic acid and its associated redox partner dihydrolipoic acid have strongly antioxidative and sometimes also pro-oxidative properties, which is why α-lipoic acid is also referred to as a "universal antioxidant." As a pharmaceutical active ingredient or as a food additive, racemic α-lipoic acid comes both as a pure solid in admixture with other components , in solid galenic formulations but also in infusion solutions for use.

Creatine, naturally abundant in meat, fish or breast milk, is crucial for muscle movement, metabolism and energy balance, and is therefore of similar importance as proteins, fats, carbohydrates, vitamins or minerals. More than 95% of the body's total creatine is in skeletal muscle tissue; but creatine is also detectable in the heart or brain. The endergonic phosphorylation of creatine in the mitochondria of the cells leads to a very high-energy compound Phosphocreatine, which as a buffer increases the amount of readily available energy (as ATP derived from ADP in the cytosol). Because it boosts the muscle's ability to absorb sugar, the creatine built up or taken up in muscle also enhances the hypoglycemic effect of insulin. In the human body, creatine in the liver and kidney is formed enzymatically from the amino acids glycine, arginine and methionine (as S-adenosyl-methionine); however, more than 50% of their own needs must be met by creatine intake via the diet or as a food supplement.

Phospholipids are important building blocks of cell membranes. Their amphiphilic character, which enables them to form the lipid bilayer of the cell walls, is due to the combination of a hydrophilic head group (a phosphate ester group at the central glycerol moiety) with a lipophilic long carbon chain chain of fatty acids. Ethern or sphingosinen lipidkerte formed. In addition to the structural function, many phospholipids also fulfill central metabolic functions, such as key molecules for signal transduction mechanisms, membrane fusions or membrane anchors for proteins. Various phospholipid fractions are used in the pharmaceutical industry primarily as surface-active substances since they can be used as emulsion or dispersion formers, as solubilizers or dissolution accelerators and as plasticizers. Accordingly, there are a number of applications in skin creams, ointments, aerosols and suppositories, in galenic forms of retardation as well as in parenteral or enteral nutrition. Phosphatidylserine (PS) is a low-abundant natural constituent of soya lecithin and is produced enzymatically. PS performs various structural and regulatory functions, including the stabilization of cell membranes, the repair of old or damaged cells, the absorption of calcium into the cell, the release of the messenger acetylcholine, and the activation of cell membrane-bound proteins ( eg protein kinase C, ATPase, tyrosine hydroxylase). Phosphatidylcholine (PC) is an essential component of the life and functioning of all human cells, especially liver cells. Racemic α-lipoic acid is approved for the treatment of liver diseases and neuropathies (eg diabetic polyneuropathy); their use as an effective inhibitor of the replication of HTV-1 viruses has been discussed (see Klin. Wochenschr., 1991, 69 (15), 722-724). The R-enantiomer of α-lipoic acid has been in clinical use in Germany since December 2000 and in the US since May 2001 IL A randomized, double-blind and placebo-controlled study of the administration of deprenyl and lipoic acid to HIV-viral infections was reported in Neurology 1998 , 50 (3), 645-651, with no improvement in cognitive ability observed for lipoic acid alone. The use of lipoic acid to treat schizophrenia has been described in Osp. psichiat, Nap 1957, 25 (2), 221-8 and AMA Arch. Internals! Med. 1959, 103, 726-9. In the latter study, five out of six patients were diagnosed with high-dose lipoic acid administration. WO 99/51097 describes the combination of creatine, creatine phosphate or creatine analogs with a neuroprotective agent such as lipoic acid for the treatment of nervous system disorders. WO 96/14063 A1 describes the sole use of creatine, creatine phosphate or creatine analogues for the treatment of such disorders of the nervous system. A study on the use of lipoic acid as a co-medication for patients with dementia of the Alzheimer's type can be found in Arch. Gerontol Geriatr. 2001, 32 (3), 275-282. WO 00/61537 A1 teaches the synthesis of lipoic acid-containing formulations and their use in the treatment of oxidative stress and endothelial dysfunction without creatine and / or phospholipids being included in the corresponding formulations. WO 01/32168 A1 combines L-carnitine with a physiologically active antioxidant (including lipoic acid) for the treatment of mild forgetfulness. Annais of the New York Academy of Sciences 1994, 717, 122-8 describes the beneficial effect of lipoic acid on the perception of rodents, and according to Pharmacol. Biochem. Behav.1993, 46 (4), 799-805, lipoic acid delivery improves the memory of mice. In the

4220851 Al was the administration of S - (-) - α-lipoic acid to rats and the resulting positive effect on the excitation of the central nervous system described. WO 00/53176 Al describes the use of novel pharmaceutical, dietary or cosmetic formulations based on lipoic acid and cysteine and their use in compensating for changes in the anaerobic and aerobic energy balance and in the treatment of complications due to oxidative stress. According to J. Rev. Medico-chirurgic. Malad. Foie 1966, 41 (1), 7-18 was able to treat acute liver atrophy with a formulation containing lipoic acid and coenzyme A. In FASEB J. 1999, 13 (2), 411-8, the administration of R - (+) - lipoic acid in aged rats was found to improve mitochondrial function and reduce the extent of oxidative damage. DE 198 30 768 A1 describes a creatine and lipoic acid containing, but phospholipid-free medicinal tea for the treatment of muscular dystrophy, and WO 01/21208 Aldie preparation of lipoic acid and carnitine containing beverages, instant powders, puddings and bars with optional addition of creatine. WO 00/10408 A1 describes the preparation of food additives with lipoic acid and creatine with a third component (preferably dextrose) for athletes to increase individual strength and muscle size. According to US 6,277,842 Bl, the supply of L-carnitine, chromium picolinate, coenzyme Q10, creatine, lipoic acid, niacin, pyravate, riboflavin and thiamine should be a prerequisite for a reduction in body weight and fat reduction. From phosphatidylserine, it is known from a number of studies that its supplementation in the form of a food supplement can increase memory and concentration ability as well as improve associated cognitive abilities. In a critical evaluation of the antioxidant properties of lipoic acid and dihydrolipoic acid, Free Radicάl Res. 1994, 20 (2), 119-33 found inhibition of lipid peroxidation in phospholipid liposomes in the brains of oxen.

The combination of the three described compounds lipoic acid (and / or derivative), creatine (or analogs) and phospholipid, for example. In a pharmaceutical, dietetic or cosmetic dosage form, however, is not yet known or described.

Object of the present invention, it was thus, by such Combining the advantages of the respective components in a common composition and to overcome existing shortcomings of previously known dosage forms of the individual components or combinations of at most two of these components. Synergistic, quantitatively enhanced or even qualitatively novel relationships between the components were not to be expected per se.

The lability of racemic or enantiomerically pure α-lipoic acid to light and temperature and a general tendency to polymerize is known to be a considerable disadvantage. However, a combination with creatine analogues and phospholipids in the context of the present invention surprisingly results in a considerable stabilization of α-lipoic acid towards light- or temperature-induced decomposition or polymerization. Although racemic or enantiomerically pure dihydrolipoic acid is resistant to polymerization under normal conditions of use, it has a high affinity for oxygen or other mild or strong oxidizing agents. On the other hand, in dosage forms according to the invention, a considerably increased oxidation stability of dihydrolipoic acid in the presence of air or an enriched oxygen atmosphere is unexpectedly recorded. Creatine cyclized in aqueous solution with a half-life in the lower hour range to the physiological renal excretion creatinine; This is surprisingly also effectively prevented in the dosage forms according to the invention. In many application examples it was found that the compositions according to the invention exceeded in their activity the corresponding summed efficiencies of the individual components (in the same dosage), which indicates synergistic mechanisms of action between the individual components. In some cases, even effects were achieved that could not previously be attributed to any of the three components. Further advantages of the present disclosure result from the simplicity of the preparation of the corresponding compositions, the uncomplicated application and the universality of possible applications.

As lipoic acid component (a) come for the claimed composition according to the invention, in particular racemic α-lipoic acid, enantiomerically pure R-

(+) - or S - (-) - α-lipoic acid or any mixtures thereof, as well as racemic dihydrolipoic acid (6,8-dimercaptooctanoic acid), enantiomerically pure R- (-) - or S - (+) - dihydrolipoic acid or any mixtures it. Furthermore, the α-lipoic acid or dihydrolipoic acid may also be wholly or partly in the form of their salts.

As a particularly suitable creatine component (b) have compounds from the

Creatine, creatine monohydrate, creatinine, creatine ascorbate, creatine dihydroascorbate, creatine / citric acid compounds in the molar ratio

1: 1 to 5: 1, preferably 1: 1 to 3: 1, creatine α-ketoglutarate, creatine pyruvate, creatine phosphate, creatine acetate, creatine folate, creatine dihydrolipoate, creatine lipoate, creatinol, their salts and derivatives such as e.g. Creatine ester proved.

As phospholipid component (c) are compounds from the class of phosphatidic acids, glycerol phospholipids (glycerol phosphatides),

Sphingophospholipids or plasmalogens are preferred, with phosphatidylserine (PS), phosphatidylcholine (PC), phosphatidylethanolamine (PE), cardiolipin, 3-phosphatidylglycerol (PG), 3-phosphatidylglycerol-1-P or phosphatidylinositol (PI) being considered particularly suitable.

The preparation, isolation and / or purification of racemic α-lipoic acid, enantiomerically pure or enantiomerically enriched R - (+) - or S - (-) - α-lipoic acid and their salts and mixtures as well as creatine, creatine phosphate or creatine analogues and phospholipids takes place in a known or analogous manner.

The lipoic acid component (a) should in proportions of 0.01 to 80 wt .-%, preferably in proportions of 0.1 to 50.0 wt .-% and particularly preferably in proportions of 1.0 to 25.0 wt .-%, in each case based on the total weight of the components (a), (b) and (c) in the composition. All parts by weight given here with respect to component (a) are racemic or optically pure α-lipoic acid. This means that when using lipoic acid derivatives or salts, the stated amounts of dosages correspond to those of the free lipoic acid, and thus have to be adapted to the changed molecular weight. The creatine component (b) should be present in proportions of I ₅ O to 99.9% by weight, preferably in proportions of 5.0 to 99.0% by weight and more preferably in fractions of 25.0 to 90, 0% by weight, again in each case based on the total weight of components (a), (b) and (c) in the composition. All parts by weight given in relation to component (b) are based on pure creatine, which means that when creatine monohydrate or creatine salts are used, the stated amounts of the dosages correspond to those of free creatine and must therefore be adapted to the changed molecular weight. The phospholipid component (c) should be present in proportions of from 0.01 to 80.0% by weight, preferably in proportions of from 0.1 to 50.0% by weight and more preferably in fractions of from 1.0 to 25, 0 wt .-%, in each case based on the total weight of components (a), (b) and (c) are used in the composition, wherein stated weight proportions with respect to component (c) directly to the respective used phospholipid or mixture of phospholipids Respectively.

In addition, the use of other conventional auxiliaries, such as binders (eg ethylcellulose, hydroxyethylcellulose, carboxymethylcellulose, starch, gelatin, polyglycols, polyacrylates, polyvinylpyrrolidone, polyvinyl alcohols and their copolymers, alginates, sucrose, glucose or polysaccharides such as pectin, gum arabic , Guar gum), fillers (such as cellulose or cellulose derivatives, glucose, fructose, sucrose, calcium phosphates, calcium sulfates, calcium carbonates, starch or modified starch, mannitol or sorbitol), disintegrants (such as cellulose or cellulose derivatives, alginates, starch or modified starch), wetting agents (such as sodium salts of aliphatic sulfonic acids such as sodium lauryl sulfate, sodium diocryl sulfosuccinate or polysorbates), flow aids (such as colloidal silica, talc or magnesium stearate), lubricants (such as magnesium stearate, calcium stearate, stearic acid, DL-leucine, talc, polyglycols, fatty alcohols or waxes) or counter-adhesives (such as starch or modified starch, magnesium stearate, Talc or DL-leucine) within the scope of the invention described herein, individually or in combinations.

The composition according to the invention can preferably be administered in medicaments, as nutritional supplements, foods, drinks and / or in cosmetics, in particular by means of peroral, dermal, parenteral, enteral, rectal, vaginal or topical application. The proposed

Composition can i.a. in gels, semi-solid formulations or solid

Solutions as well as beverages, effervescent or instant powders, puddings, yoghurts or bars. In addition, it is expressly suitable for use in a supplementary or combination therapy.

The administration of the composition according to the invention is ideally carried out in a single dose between 10 mg and 10 g, preferably between 0.5 and 5.0 g. The daily dose of the composition according to the invention should be between 30 mg and 50 g, preferably between 1.0 and 20 g. The proportion of the three components (a), (b) and (c) of the composition according to the invention can be varied within the specified limits.

The person skilled in the art is sufficiently familiar with suitable examination methods and assays for testing possible somatic and psychological effects with regard to the bioactivity of the mixtures and salts according to the invention. For example, arteriosclerotic or vasodilatory effects as well as circulatory disorders can be determined with the aid of flow-mediated progression (flow-induced dilation, FMD). Extensive measurement methods are available for determining the blood glucose value (eg oral glucose tolerance test, OGTT), hyperlipoproteinemia (eg lipoprotein electrophoresis with subsequent ultracentrifugation) as well as insulin sensitivity and insulin resistance (eg insulin glucose tolerance test, IGTT). For the qualitative and quantitative determination of oxidative stress, for example, the effect of reactive oxygen and nitrogen compounds on redox-active enzymes by means of enzyme kinetic and structural analysis of body-own proteins can be used. To determine the mitochondrial function In particular, the content of cardiolipin as a parameter is suitable (compare, for example, Neurochem., 1994, 25, 295-300). The damaging extent of photodermatoses can be categorized by comparative observations, identification of the skin flora, and determination of relative skin hydration. General and specific parameters are used to determine aging effects (activity, appearance, wrinkling, wound healing, renal function), dementia disorders (memory, forgetfulness, thinking, judgment, intelligence, orientation ability), psychosis (delusions, hallucinations) and other cognitive factors (irritability, stubbornness) , Hypersensitivity, anxiety, mental disability, guilt, speech disorders, psychomotor disorders, ambivalence, agitation, melancholy, stereotypies, autism). There are also methods for the diagnosis of neurodegenerative deficits and cerebral dysfunctions, such as epilepsy (anamnesis, electroencephalography (EEG), magnetic resonance imaging) or phenylketonuria (Guthrie test in neonates, heterozygote detection). In Alzheimer's disease - the fourth leading cause of death in industrialized countries (5 - 20% of 65 to 80 year olds are affected) - is a diagnosis of living people after the onset of typical symptoms (initially memory disorders, later increasingly restlessness Forgetfulness, poor concentration, spatial disturbances), on the other hand, can only be achieved by excluding similar diseases. A definitive diagnosis can only be made post-mortem. In neurological examination, extrapyrimidal syndromes or pyramidal tract signs occur in rare cases.

The present invention also generally includes the ability to use the claimed composition to produce an agent that is suitable for slowing down degenerative and, in particular, progressive brain changes. Alternatively or additionally, the use for the preparation of an agent for the treatment and alleviation of complications and symptoms associated with schizophrenia, dementia, organic psychosis or cognitive dissonance in question. In addition, the present invention provides the possibility of the composition for the preparation of an agent for the treatment of dementia infantilis, phenylketonuria, Alzheimer's Disease, Huntington's disease (Huntington's disease), epilepsy, Pick's disease, Binswanger's disease, Friedreich's ataxia, ParMnson's syndrome, Down syndrome, HIV disease, or Creutzfeldt-Jakob disease, or for the preparation of an agent for treatment of metabolic or degenerative diseases of the cerebral nerve tissue, in particular for the treatment of cerebral atrophy and brain-localized atrophy due to local circulatory disorders.

Also included is the alternative of use for the preparation of an agent for treating complications associated with

Aging phenomena of cell structures, in particular for the treatment of

Age brain, producing a remedy for mitochondrial

Function, and / or the preparation of an agent for the treatment of

Complications related to type II diabetes, hyperglycemia and / or compensated or decompensated insulin resistance.

As another related alternative use, the present invention contemplates the preparation of an agent for the treatment of complications associated with atherosclerosis, an agent for treating complications associated with endothelial dysfunction, an agent for the treatment of complications associated with oxidative stress, an agent for the treatment of Complications associated with impaired lipid metabolism, as well as the production of a scar tissue treatment agent.

Furthermore, the possibility is taken to use the composition for the preparation of an agent used before, during and after radiotherapy or X-ray examination, as well as for the treatment of effects caused by ionizing radiation or for the preparation of an agent for treating symptoms in the body Related to somatogenic, endogenous, psychogenic or pharmacogenic depression, for the preparation of an agent for the improvement of cognitive functions and for the treatment of mental or memory disorders and as anorectic. However, it is also the use of the composition for the preparation of an agent for the treatment of dystrophies and mitochondrial, metabolic or endocrine myopathies, in particular Duchenne-type x-linked recessive dystrophies and myotonic dystrophies (Curschmann-Steinert-Batten syndrome), hyperthyroidism, Hypothyroidism and Cushing syndrome I as well as mitochondrial encephalomyopathies, as well as the use for the preparation of an agent for the prevention or support of therapeutic measures during healing, convalescence, remission, regeneration or rehabilitation after open or closed grade 1 to 4 fractures Framework of reduction, retention, immobilization, occupational therapy or physiotherapy.

The following examples illustrate the advantages of the claimed composition and its application.

Belspiele

Example 1: 500 mg gelatin capsules each containing: (±) -α-lipoic acid 60 mg

Creatine monohydrate 400 mg

Phosphatidylserine 40 mg

These gelatine capsules are used to increase brain function and, in particular, memory performance, administered orally three times a day. The daily dose of the dosage form is 1.5 g.

Example Z. Gelatin capsules with a sustained action of 500 mg each, containing: (±) -dihydrolipoic acid 50 mg

Creatine citrate 300 mg

Phosphatidylserine 50 mg

Excipients 100 mg

These gelatin capsules for invigorating and even memory enhancement are administered orally twice a day. The daily dose of

Dosage form is 0.8 g.

Example 3:

50 g of a effervescent powder containing S - (+) - α-lipoic acid (80% ee) 5.0 g

Creatine monohydrate 25.0 g

Phosphatidylglycerol 5.0 g

Excipients 15.0 g

The effervescent powder is dissolved in 2 g portions in water or stirred into yogurt and absorbed orally. The daily dose of the dosage form for

Increasing the mental fitness is 10 g.

Examples 4 to 6 also serve to increase attention and Brain Power:

Example 4:

Gelatin capsules of 400 mg each, containing: (±) -dihydrolipoic acid 50 rag

Creatine monohydrate 300 mg

Phosphatidylcholine 50 mg

These gelatin capsules are administered orally three times a day. The daily dose of the dosage form is 1.2 g.

Example 5:

One 600 mg tablet containing: R - (+) - α-lipoic acid (99% ee) 150 mg

Creatine Monohydrate 400 mg Phosphatidylserine 50 mg

These tablets are administered orally four times a day. The daily dose of the dosage form is 2.4 g.

Example 6: 400 mg gelatin capsules containing:

(±) -α-lipoic acid 50 mg

Creatine pyruvate 300 mg

Phosphatidylinositol 50 mg

Excipients 100 mg These gelatin capsules are administered orally four times a day. The daily dose of the dosage form is 1.6 g.

Example 7:

10g of a skin cream containing:

(±) -α-lipoic acid 1.0 g

Creatine citrate 6.0 g

Phosphatidylserine 0.5 g

Excipients 2.5 g The skin cream is applied to skin areas exposed to sunlight. The daily dose of the dosage form is about 5 g.

The data from respective applications of the dosage forms according to the invention on isolated cells, animals and humans show an overall reduced formation of reactive oxygen particles, reduced oxidative stress and reduced aging effects such as e.g. increased muscular activity, delayed fatigue or increased activity. When administered to humans, the ability to concentrate, think and remember is increased; in pathological cases of somatogenic, psychogenic or pharmacogenic depression, there is a significant improvement in affectivity (such as a positive mood of grandeur, the elimination of joylessness, passivity and inferiority, reduction of irritability, hypersensitivity and grief reactions). In parallel, this is often accompanied by a reduction in appetite, a reduction in the amount of food consumed and a reduction in weight.

Furthermore, in particular in the case of peroral or intravenous administration of the dosage form according to the invention, antihyperglycemic effects as well as an increased insulin sensitivity and reduced insulin resistance are associated. Flow-mediated dilatation (FMD) also has positive effects after administration of the pharmaceutical dosage forms according to the invention described in the examples. Hypolipoproteinemias, hypercholesterolemias and lipidoses are significantly reduced. The wound closure of wounded or destroyed tissue and the regeneration of granulation or scar tissue in the course of wound healing are significantly accelerated, especially in the reparative phase. After topical application of a cosmetic or pharmaceutical dosage form according to the invention, skin redness, sunburn and other photodermatoses, efflorescences, eczema and emphysema as well as other effects attributable to the action of ionizing radiation (in the context of radiotherapy, X-ray examinations or permanent or temporary exposure to cosmic radiation) are significantly reduced.

Claims

claims 1. Physiologically acceptable composition comprising (a) α-lipoic acid and / or one of its derivatives, (b) creatine and / or one of its derivatives and (c) a phospholipid. 2. Composition according to claim 1, characterized in that the component comprises (a) a racemic lipoic acid, an enantiomerically pure R - (+) - or S - (-) - α-lipoic acid or any mixtures thereof. 3. The composition according to claim 1, characterized in that the component (a) is a racemic dihydrolipoic acid, an enantiomerically pure R - (-) - or S - (+) - α ~ Dihydroliponsäure or any mixtures thereof. 4. Composition according to one of claims 1 to 3, characterized in that the α-lipoic acid or dihydrolipoic acid is present wholly or partly in the form of their salts. 5. Composition according to one of claims 1 to 4, characterized in that component (b) at least one compound from the group creatine, creatine monohydrate, creatinine, creatine ascorbate, creatine dihydro ascorbate, creatine / citric acid compounds in a molar ratio 1: 1 up to 3: 1, creatine α-ketoglutarate, creatine pyruvate, creatine phosphate, creatine acetate, creatine folate, creatine dihydrolipoate, creatine lipoate, creatinol, their salts and derivatives such as Creatine ester is. 6. The composition according to any one of claims 1 to 5, characterized in that component (c) at least one compound from the class of phosphatidic acids, glycerol phospholipids, such as phosphatides, plasmalogens or sphingophospholipids. 7. The composition according to any one of claims 1 to 6, characterized in that component (c) at least one compound from the group phosphatidylcholine (PC), phosphatidylserine (PS) ₅ phosphatidylethanolamine (PE), phosphatidylinositol (PI), cardiolipin, 3-phosphatidylglycerol-1-P or 3-phosphatidylglycerol (PG). 8. The composition according to any one of claims 1 to 7, characterized in that the lipoic acid component (a) in proportions of 0.01 to 80.0 wt .-%, preferably in proportions of 0.1 to 50.0 wt. %, particularly preferably in proportions of from 1.0 to 25.0% by weight, based in each case on the total weight of components (a), (b) and (c), of the composition. 9. Composition according to one of claims 1 to 8, characterized in that the creatine component (b) in proportions of 1.0 to 99.9 wt .-%, preferably in proportions of 5.0 to 99.0 wt. %, particularly preferably in proportions of from 25.0 to 90.0% by weight, in each case based on the total weight of components (a), (b) and (c), of the composition. 10. The composition according to any one of claims 1 to 9, characterized in that the phospholipid component (c) in proportions of 0.01 to 80.0 wt .-%, preferably in proportions of 0.1 to 50.0 wt. -%, particularly preferably in proportions of 1.0 to 25.0 wt .-%, each based on the total weight of components (a), (b) and (c) is contained in the composition. 11. Use of the composition according to any one of claims 1 to 10 for the preparation of an agent for the slowing down of degenerative and especially progressive brain changes. 12. Use of the composition according to any one of claims 1 to 10 for the manufacture of an agent for the treatment and alleviation of complications and symptoms associated with schizophrenia, dementia, organic Psychosis or cognitive dissonance. 13. Use of the composition according to any one of claims 1 to 10 for the manufacture of an agent for the treatment of infantile dementia, phenylketonuria, Alzheimer's disease, Huntington's chorea (Veitstanz), Epilepsy, Pick's disease, Binswanger's disease, Friedreich's ataxia, Parkinson's syndrome, Down syndrome, HIV disease or Creutzfeldt-Jakob disease. 14. Use of the composition according to any one of claims 1 to 10 for the preparation of an agent for the treatment of metabolic or degenerative diseases of the cerebral nerve tissue, in particular for the treatment of cerebral atrophy and brain-localized atrophy due to local circulatory disorders. 15. Use of the composition according to one of claims 1 to 10 for the preparation of an agent for the treatment of complications associated with aging phenomena of cell structures, in particular for the treatment of geriatric brain. 16. Use of the composition according to any one of claims 1 to 10 for the preparation of an agent for improving mitochondrial function. 17. Use of the composition according to any one of claims 1 to 10 for the preparation of an agent for the treatment of complications in Related to type II diabetes, hyperglycemia and / or compensated or decompensated insulin resistance. 18. Use of the composition according to any one of claims 1 to 10 for the preparation of an agent for the treatment of complications in Related to arteriosclerosis. 19. Use of the composition according to one of claims 1 to 10 for Preparation of an agent for the treatment of complications associated with endothelial dysfunction. 20. Use of the composition according to any one of claims 1 to 10 for the preparation of an agent for the treatment of complications in Related to oxidative stress. 21. Use of the composition according to any one of claims 1 to 10 for the manufacture of an agent for the treatment of complications associated with a disturbed lipid metabolism. 22. Use of the composition according to any one of claims 1 to 10 for the manufacture of a means for the treatment of scarred tissue. 23. Use of the composition according to any one of claims 1 to 10 for the preparation of an agent which is used before, during and after radiotherapy or X-ray examination and for the treatment of effects caused by ionizing radiation. 24. Use of the composition according to any one of claims 1 to 10 for the preparation of a Mittelis for the treatment of symptoms associated with somatogenic, endogenous, psychogenic or pharmacogenic depression. 25. Use of the composition according to one of claims 1 to 10 for the preparation of an agent for improving cognitive functions and for Treatment of mental or memory disorders. 26. Use of the composition according to any one of claims 1 to 10 as an anorectic. 27. Use of the composition according to any one of claims 1 to 10 for the preparation of an agent for the treatment of dystrophies and mitochondrial, metabolic or endocrine myopathies, in particular x- Duchenne-type chromosomal recessive dystrophy and myotonic dystrophy (Curschmann-Steinert-Batten syndrome), hyperthyroidism, hypothyroidism and Cushing syndrome I, and mitochondrial encephalomyopathies. 28. Use of the composition according to any one of claims 1 to 10 for the preparation of an agent for the prevention or support of therapeutic measures during healing, convalescence, remission, regeneration or rehabilitation after open or closed fractures of grade 1 to 4 in the context of reduction , Retention, Immobilization, occupational therapy or physiotherapy. 29. Use according to any one of claims 11 to 28, wherein the amount of the composition is between 10 mg and 10 g, preferably between 0.5 and 5.0 g per single dose. 30. Use according to any one of claims 11 to 28, wherein the amount of the composition is between 30 mg and 50 g, preferably between 1.0 and 20 g per daily dose. 31. Use according to one of claims 1 to 10 as dietary supplements, foods, drinks, in medicines and / or in cosmetics. 32. Use according to claim 31 in peroral, dermal, parenteral, enteral, rectal, vaginal or local (topical) applications. 33. Use according to any one of claims 31 and 32 in gels, semi-solid dosage forms or solid solutions and in beverages, effervescent or instant powders, puddings, yoghurts or bars. 34. Use of the composition according to any one of claims 1 to 10 in the context of a supplementary or combination therapy.