RU2299724C1 - Agent improving physiological state of skin cells - Google Patents

Abstract

FIELD: cosmetology, medicine, dermatology.

SUBSTANCE: invention relates to agents showing favorable effects of function of cutaneous tissue cells. Proposed agent improving physiological state of skin cells comprises alpha-lipoic acid R-form and/or its derivatives, and/or its metabolic precursors as an active component of cosmetic and/or dermatological agents wherein the content of the proposed agent is from 0.1 to 10.0 weight%, and an acceptable carrier also. The proposed agent recoveries and maintains homeostasis of cutaneous tissue and allows improving physiological state of cutaneous tissues, protecting its against unfavorable and damage effects and to prolong active youth of cells.

EFFECT: valuable medicinal and cosmetic properties of agent.

2 cl, 9 dwg, 2 ex

Description

The invention relates to the field of cosmetology and dermatology and relates to appropriate agents that positively affect the functioning of skin tissue cells.

The skin is the outer protective cover of the body and performs a variety of physiological functions: protective, receptor, metabolic.

The metabolic functions of the skin (excretory, absorbing, respiratory) actively provide its main task: to be a protective barrier of the body, to maintain the constancy of its internal environment or homeostasis. The skin is involved in respiration, produces vitamin D and stores vitamin A. It plays a significant role in the metabolism of carbohydrates, lipids, and proteins. By the intensity of water, mineral and carbon metabolism, the skin is only slightly inferior to the liver and muscles.

With age and with the adverse effects of the external and internal environment in the skin, the processes of epidermal regeneration decrease, the content of water and cellular elements in the dermis decreases, the susceptibility to the action of damaging factors increases; metabolic processes in skin tissues slow down, the functioning of skin tissue cells is disrupted; the skin loses elasticity, the relief of the epidermis changes.

Numerous cosmetic and dermatological products are known for normalizing the impaired functions of skin tissues.

For example, dermatological and cosmetic anti-aging compositions are known which contain emulsifying agents, polyethylene glycol mono- or distearate, polyglycol esters of saturated or unsaturated fatty acids, cetyl alcohol, sodium versenate and antioxidizing agents (vitamins of group F, tocopherol derivatives), bacteriostatic and anti-mold agents (methyl or propyl p-hydroxybenzoate), active ingredients (collagens, esurosamine, elastin, amino acids, peptides, mucopolysaccharides) and purified in ode. The base and excipients of the composition have stabilizing activity with respect to active ingredients that undergo decomposition under environmental conditions [RF Patent 2.076.693, A61K 7/00, 1994].

A face cream is described that is effective for dry, aging skin, has regenerative ability and activates metabolic processes and blood microcirculation, which contains water-alcohol extract of aloe, honey, water extract of rose petals, mink fat [RF Patent 2.170.081, A61K 7/48, 2000].

Known cream for face and body skin, normalizing metabolic processes in the skin and stimulating local immunity, which contains a mixture of biologically active polypeptides extracted from koumiss [RF Patent 2.137.467, A61K 7/48, 1999].

A cosmetic product with immunomodulating and anti-aging effects has been patented, which includes therapeutic mud, sapropel, blue clay and kaolin [RF Patent 2.180.213, A61K 7/48, 2002].

However, as a rule, all known means designed to normalize impaired skin functions are aimed at stimulating individual processes that occur in it, and not at optimizing metabolic processes in general, which can lead to unilateral depletion of its reserves and, ultimately, to violation of her homeostasis. In addition, stimulation of pathological processes occurring in the skin is possible.

The technical task of the present invention is to create cosmetic and / or dermatological products that restore and maintain homeostasis of the skin by optimizing the metabolic processes in the skin tissue, updating the composition of cells and extracellular components of the skin. All this allows you to improve the physiological condition of the skin, protect them from the adverse effects of damaging factors and extend the active youth of the cells.

The problem was solved as a result of using the R-form of alpha-lipoic acid and / or its derivatives and / or its metabolic precursors as the active ingredient in cosmetics.

The outer layer of the skin - the epidermis is completely renewed (regenerates) on average every 52-75 days. An individual cell needs an average of 28 days to go the whole way of differentiation or specialized development from birth in the deepest - basal layer of the epidermis to death and desquamation in the stratum corneum.

To maintain homeostasis of the skin or physiological equilibrium of the epidermis, it is necessary to maintain a balance between the proliferation or multiplication of cells in the basal layer of the epidermis and the process of differentiation or specialization of cells to perform their functions on the skin surface. Any deviation in one or the other direction under the influence of damaging external and internal factors leads to the development of pathological processes. For example, increased proliferation without accompanying support by differentiation processes can lead to psoriasis, and, conversely, the predominance of differentiation over proliferation processes to hyperkeratosis.

With age, the level of metabolic processes that characterize the homeostasis of a young organism gradually decreases. This is accompanied by a decrease in the total energy supply of the body or the amount of ATP synthesized in the mitochondria of cells, an increase in the level of free radicals, and a decrease in the severity of intracellular structures responsible for the synthesis of new molecules. As a result, the epidermis regeneration process slows down, new cells form less and less, they do not replace the old ones, which linger longer and longer on the surface of the skin. The process of natural desquamation or desquamation of horny scales slows down.

The general ratio of old and new cells in the epidermis shifts toward the former, moreover, the ratio of the thickness of the epidermis layers shifts toward a decrease in the layer of living cells. The surface of the skin becomes uneven, its elasticity and hydration deteriorate, its barrier functions fall sharply.

As the studies of the applicant have shown, the use in cosmetic and / or dermatological products of the R-form of alpha-lipoic acid and / or its derivatives and / or its metabolic precursors allows not only to regulate and maintain homeostasis, but also to restore its level characteristic of a young and healthy organism.

Under the derivatives of the R-form of alpha-lipoic acid refers to its chemical derivatives containing various reactive groups.

As examples that do not exhaust all the options, we can cite the most famous derivatives of alpha lipoic acid - its salts (especially alkali metal salts), esters (especially fatty acid esters) and amides (especially isolated from natural lipoamides or their analogues), as well as the reduced form of alpha lipoic acid - dihydrolipoic acid and its salts, esters and amides.

Currently, it is known to use alpha lipoic acid in cosmetology, which is used as an antioxidant and anti-inflammatory drug, treat acne and scars from it (US Patent No. 6365623, 2002), erythema, protect the skin from ultraviolet radiation and its effects ( U.S. Patent No. 6,752,999, 2004)

It is known to use alpha lipoic acid as an oral drug. In medicine, it is used to treat vitamin deficiency, diabetes, diabetic neuropathy, multiple sclerosis, hyperlipidemia and hyperlipoproteinemia (US Patent No. 6,518,300, 2003), stimulate blood circulation after hypoxia (Hagen, T, Ingersoll R, et al. R-lipoic acid-supplemented old rats have improved mitochondrial function, decrease oxidative damage, and increase metabolic rate. FASEB 13: 411-418, 1999), used as a hepatoprotector for cirrhosis, treat various viral infections, including AIDS.

In bodybuilding, lipoic acid is used to build muscle (US Patent No. 6,620,425, 2003).

Alpha-lipoic acid (α-lipoic acid) was discovered in 1948, isolated in 1951. It is formed as a result of biosynthesis in plant and animal cells, found in spinach, potatoes, tomatoes, and broccoli. It is synthesized by mammalian body cells. With age and under the influence of adverse environmental factors, its amount in the body becomes insufficient. The consequence of this is an increased sensitivity of the body to adverse external and internal factors.

α-lipoic acid has the general formula C ₈ H ₁₄ O ₂ S ₂ . Its structural formula:

α-lipoic acid has two stereoisomers - R- and S-enantiomers. The R-form is a natural stereoisomer and differs in biochemical properties from the S-form.

Until recently, only the racemic mixture of two isomers of lipoic acid was widely used. However, it has been shown that, when used internally, the mixture of isomers has a tens of times less pronounced effect than the pure R-form (US Patent No. 5728735, 1998). Moreover, in some cases, the S-form when using a racemate even inhibits the activity of the R-form.

Based on these facts, the applicant suggested that the use of the R-form of α-lipoic acid for cutaneous use would also be more effective than using a mixture of isomers. However, as a result of experimental studies carried out by the applicant, not only the great efficiency of using the R-form of α-lipoic acid was confirmed, but a number of effects not previously described with cutaneous application of α-lipoic acid were identified and confirmed.

So, the R-form of α-lipoic acid protects skin cells from various pathological manifestations, and the combination of enhanced cellular respiration and protection against possible negative oxidative properties of oxygen has a positive effect on the condition of the skin. The R-form of α-lipoic acid normalizes the structural and functional state of the energy system of skin cells and creates the prerequisites for enhancing protein synthesis. In general, the physiological state of the skin improves, its qualitative and quantitative composition is optimized both at the cellular and intercellular levels.

All this allows you to restore and maintain homeostasis of the skin, its new level, characteristic of a young and healthy body, regardless of chronological age.

To confirm the above, the applicant conducted the following studies:

1. The intensity of proliferation (mitotic index) and death (apoptotic index) of cultured human keratinocytes when exposed to different forms of α-lipoic acid are compared. The predominant effect of the R-form compared to the racemate on the possibility of accelerating the renewal of the cellular composition of the epidermis is shown.

2. The energy state of mitochondria in epidermal cultured cells stained with a voltage-dependent dye (rhodamine 123) under the action of various forms of α-lipoic acid was studied by luminescent microscopy. It was shown that it is the R-form of α-lipoic acid that creates a high energy level in all cells of the population.

3. The method of light microscopy was used to study the structure of the skin of mice after applying emulsions containing different forms of α-lipoic acid to the skin. The predominant effect of the R-form of α-lipoic acid on increasing the thickness of the layers of living cells in the epidermis and extracellular matrix in the dermis, as well as the number of organelles involved in protein synthesis, was found. These data indicate an improvement in the qualitative and quantitative composition of skin cells and an increase in their physiological activity.

The following is a description of in vitro and in vivo studies and the results obtained.

1. The intensity of proliferation and death of cultured human keratinocytes of the A431 line under the influence of different forms of α-lipoic acid (R- and R, S-forms) is compared. A431 culture was grown on DMEM medium supplemented with 10% fetal cattle serum and 80 μg / ml gentamicin at 37 ° C. Cells were removed from the glass with Versen's solution and trypsin (3: 1), suspended in fresh medium and planted on coverslips in Petri dishes. After 24 hours, the sodium salt of the R- or R, S-form of α-lipoic acid (100 μM) was introduced into the culture medium. As a control, cells cultured without administration of α-lipoic acid were used.

After 24 hours, the cells were fixed with methanol (-20 ° C) and stained with hematoxylin for subsequent statistical processing. The stained cells were placed in running water for 5 minutes, then transferred to distilled water, 70 °, 96 °, 100 ° alcohols, then placed in xylene and enclosed in Canadian balsam to obtain permanent preparations.

When calculating the mitotic and apoptotic index, the calculation was carried out on 1000 cells from two different glasses for each type of treatment. Statistical analysis was performed in Microsoft Excel.

Counting the number of mitotic cells showed that the action of all forms of α-lipoic acid used by us in this experiment does not affect the intensity of cell division: the mitotic index averages 4.5%. But when analyzing the ratio of different phases of mitosis, a clear decrease in the proportion of prometaphase cells was detected under the action of the R-form of α-lipoic acid (Figure 1 shows the effect of various forms of α-lipoic acid on the phase ratio of mitotic cell division of A431 keratinocytes culture.

Legend:

R-Na - sodium salt of the R-form of α-lipoic acid

RS-Na is the sodium salt of the R, S-form of α-lipoic acid).

This means accelerating the passage of this most energy-consuming and vulnerable phase of mitosis, in which complex processes of formation of the spindle of division and the alignment of chromosomes in the metaphase plate take place. The data obtained indicate that under the action of the R-form of α-lipoic acid, not only the energy supply of the cell in mitosis improves, but also there is a qualitative change in the process of cell division.

The study of the nature of cell death showed that both in the control culture and under the action of various forms of α-lipoic acid, cells die by apoptosis. Calculation of the number of apoptotic cells showed that the effect of α-lipoic acid on cells in these experimental conditions is not toxic, since the proportion of dying cells remains at a low level - about 1%. However, at the same time, the stimulating effect of R - α-lipoic acid is revealed both in comparison with the control and with the R, S-form on this process (Figure 2 shows the percentage of apoptotic cells when exposed to various forms of α-lipoic acid on culture cells keratinocytes A431.

Legend:

R-Na - sodium salt of the R-form of α-lipoic acid

RS-Na is the sodium salt of the R, S-form of α-lipoic acid).

This means that the action of the R-form of α-lipoic acid can accelerate the process of updating the keratinocyte population by removing damaged cells from its composition.

2. The method of luminescence microscopy was used to study the state of mitochondria in cultured epidermal cells of the SPEV line stained with a voltage-dependent dye, rhodamine 123 under the action of the R and R, S forms of α-lipoic acid. For this, culture cells were grown on medium 199 with the addition of 10% cattle serum and 80 μg / ml gentamicin at 37 ° C. Cells were removed from the glass with Versen's solution and trypsin (3: 1), suspended in fresh medium and planted on coverslips in Petri dishes. After 24 hours, the R- or R, S-form of α-lipoic acid (100 μM) was introduced into the culture medium, and cells cultured without α-lipoic acid were used as a control. After another 24 hours, the cells were stained with Rhodamine 123, an intravital voltage-dependent mitochondrial dye that reflects their high energy activity.

Rhodamine 123 was introduced into the culture medium at a concentration of 10 μg / ml for 10 minutes at 37 ° C. Next, the coverslip with cells was washed in fresh medium for 5 min at 37 ° C.

Photographing was carried out using an Opton Photo III microscope (lens 100).

Photo processing was carried out using the program Adobe Photoshop.

It was found that if in the control cultures some of the cells are weakly stained with rhodamine 123 and the effect of the R, S-form of α-lipoic acid does not change the situation, then under the action of the R-form all cells are intensively stained (Figure 3 shows the effect of the effects of various forms of α -lipoic acid on the state of the respiratory system (mitochondria) of SPEV culture cells.

Samples 1 and 2 - DMSO (control); samples 3 and 4 — R, S-form of α-lipoic acid; Samples 5 and 6 — R-form of α-lipoic acid.

Samples 1, 3, and 5 — phase contrast; samples 2, 4 and 6 — intravital staining of mitochondria by Rhodamine 123. Thus, the effect on the cell’s energy system depends on the form of α-lipoic acid: only the R-form of α-lipoic acid is able to create a high energy level in all cells of the population, regardless of its initial heterogeneity. It should be emphasized that a high bioenergetic potential of tissue cells is a necessary condition for a high level of metabolic processes in it.

3. The method of light microscopy was used to study the skin structure of the line of CBA mice after application of emulsions containing different forms of α-lipoic acid (R- and RS-) to the back surface in the region above the shoulder blades. In the work, 26 sexually mature males (4 months) and 3 old females (2 years) of the CBA line were used. The weight of males ranged from 21 to 25 grams. The weight of females is from 35 to 40 gr. Animals were kept in individual cages. Processing was carried out daily at the same time for 10 days.

The males were divided into groups of 5 animals: group No. 1 — control without applying cosmetic emulsion; group No. 2 - control with the application of an emulsion without α-lipoic acid; Group; No. 3 - application of an emulsion with 5% R, S-form of α-lipoic acid in the form of potassium salt; Group; No. 4 - applying an emulsion with a 5% R-form of α-lipoic acid in the form of potassium salt; group No. 5 - applying an emulsion with a 5% R-form of α-lipoic acid in the form of a plant extract. Two old females were treated with an emulsion containing 5% R-form of α-lipoic acid in the form of a plant extract, one female was treated as a control with an emulsion without α-lipoic acid.

Skin samples were fixed with 4% paraformaldehyde in PBS phosphate buffer at + 4 ° C, performed according to standard procedures, and enclosed in histoplast. Sections were stained with hematoxylin-eosin. Photographing was carried out using an Axiovert microscope (X20, X63, X100 lenses).

Photo processing was carried out using the program Adobe Photoshop.

) из группы №1 (без нанесения эмульсионной основы). Образец 1 - объектив Х20, образцы 2-4 - объектив Х63.Figure 4 shows skin sections of control adult animals (

) from group No. 1 (without applying an emulsion base). Sample 1 - lens X20, samples 2-4 - lens X63.

Illustrations for the study of the group of control animals No. 1.

Sample 1 of FIG. 4 shows a skin section of a control animal with a small increase (vol. X20). You can see a thin layer of the epidermis, dermis and hair follicles. On samples 2; 3 and 4, a large increase in the areas of the epidermis is given (vol. X63). The basal layer of flattened cells is traced, two layers of spiky cells are above it and horny scales are visible, but the granular and shiny layers are not clearly visible.

) из группы №2 (эмульсионная основа без липоевой кислоты). Образец 1 - объектив Х20, образцы 2-4 - объектив Х63.Figure 5 - shows skin sections of control adult animals (

) from group No. 2 (emulsion base without lipoic acid). Sample 1 - lens X20, samples 2-4 - lens X63.

Illustrations for the study of the group of control animals No. 2.

Sample 1 shows a small increase in the cut of the skin (vol. X20), in sample 2, 3 and 4, a large increase in the areas of the epidermis (vol. X63) is given. As in control No. 1, no more than three layers of cells are traced in the epidermis, followed by horny scales. Thus, the application of an emulsion base that does not contain α-lipoic acid did not lead to a change in the thickness of the epidermis and the number of cell layers in it.

However, the thickness of the dermis layer slightly increased. A significant increase in the dermis layer (up to 30% under the action of the R-form) was found when applying emulsions containing different forms of α-lipoic acid (illustrations not shown).

) из группы №3 (R,S-форма альфа-липоевой кислоты в виде калиевой соли в составе эмульсии). Образец 1 - объектив Х20, образцы 2-4 - объектив Х63, квадрат 5 - объектив Х100.Figure 6 - shows sections of the skin of adult animals (

) from group No. 3 (R, S-form of alpha-lipoic acid in the form of potassium salt in the composition of the emulsion). Sample 1 - lens X20, samples 2-4 - lens X63, square 5 - lens X100.

Illustrations for the study of animal group No. 3 treated with the R, S-form of α-lipoic acid.

On sample 1, you can see a noticeable increase in the thickness of the epidermis (vol. X20). On samples 2, 3, 4 (vol. X63) it can be seen that the basal layer is represented not only by flattened, but also by cylindrical cells. In the epidermis, there are 6-7 layers of cells, and not only the basal and spiky layers are visible, but also the granular and shiny layer (samples 4 and 5). In addition, a large number of mitotic cells are found in the epidermis (sample 5, vol. X100).

) из группы №4 (R-форма альфа-липоевой кислоты в виде калиевой соли в составе эмульсии). Образец 1 - объектив Х20, образцы 2-4 - объектив Х63, образец 5 - объектив Х100.7 shows sections of the skin of adult animals (

) from group No. 4 (R-form of alpha-lipoic acid in the form of potassium salt in the emulsion). Sample 1 - lens X20, samples 2-4 - lens X63, sample 5 - lens X100.

Illustrations for the study of animal group No. 4, treated with the R-form of α-lipoic acid in the form of potassium salt (sample 1 - vol. X20, samples 2, 3, 4 - vol. X63). As in the previous version, the epidermis is represented by large cells and a large number of layers, but when counting the layers, there are from 6 to 8, depending on the area of the skin. Mitotic figures are also visible - sample 5 (vol. X100).

) из группы №5 (R-форма α-липоевой кислоты в виде растительного экстракта в составе эмульсии). Образец 1 - объектив Х20, образцы 2-4 - объектив Х63, образец 5 - объектив Х100.On Fig shows sections of the skin of adult animals (

) from group No. 5 (R-form of α-lipoic acid in the form of a plant extract in the emulsion). Sample 1 - lens X20, samples 2-4 - lens X63, sample 5 - lens X100.

Illustrations for the study of a group of animals No. 5 treated with the R-form of α-lipoic acid in the form of a plant extract.

Even at a small increase (sample 1 - vol. X20), an even larger increase in the thickness of the epidermis is striking: the number of layers can reach 10. Moreover, up to three layers of cells can be counted in the granular layer (samples 3, 4 - about X63, sample - 5 - vol. X100). The cells of the prickly layer have large nuclei with a large number of nucleoli (sample 3). A large number of mitoses are observed in the basal and spiky layers, in almost every field of view of the microscope (samples 4, 5).

) (R-форма α-липоевой кислоты в виде растительного экстракта в составе эмульсии). Образец 1 - объектив Х20, образцы 2-4 - объектив Х63. На кожу наносили эмульсию, которая содержала R - форму α-липоевой кислоты в виде растительного экстракта. На малом (образец 1 - об. Х20) и большом увеличениях (образцы 2, 3 и 4 - об. Х63) видно такое же, как у самцов, утолщение эпидермиса - число слоев достигает 8-9. Также видны митотические клетки - образцы 2, 3.Figure 9 shows sections of the skin of old animals (old females) (

) (R-form of α-lipoic acid in the form of a plant extract in the composition of the emulsion). Sample 1 - lens X20, samples 2-4 - lens X63. An emulsion was applied to the skin, which contained the R - form of α-lipoic acid in the form of a plant extract. At small (sample 1 - vol. X20) and high magnifications (samples 2, 3 and 4 - vol. X63) the same thickening of the epidermis is seen as in males - the number of layers reaches 8-9. Mitotic cells are also visible - samples 2, 3.

Thus, the study showed that local application of any form of α-lipoic acid to the skin surface of mice leads to an increase in proliferative activity in the basal and prickly layers of the epidermis and, as a result, to an increase in the number of layers of living actively functioning cells. Moreover, simultaneously with increased proliferation in the epidermis, differentiation of cellular elements occurs and, in contrast to control groups, all structural layers are pronounced in the tissue of animals exposed to α-lipoic acid. The presence in the epidermis of large cells with nuclei having several nucleoli indicates an increase in protein synthesis and the activation of synthetic processes in general.

The described structural and functional changes in the skin are detected not only in adult males, but also in old females, which indicates that exposure to α-lipoic acid establishes a new physiological balance in the skin (homeostasis), characteristic of a young healthy body, regardless of chronological age experimental animals and their gender.

It should be emphasized that the R-form of α-lipoic acid is significantly more effective than the R, S-form.

The absolute content of the R-form of α-lipoic acid and / or its derivatives and / or its metabolic precursors in the cosmetic and / or dermatological agent can be within wide limits, but in the optimal case is from 0.1 to 10.0 wt.%.

Cosmetics containing the R-form of α-lipoic acid and / or its derivatives and / or its metabolic precursors can be prepared in the form of traditional cosmetic forms such as creams, masks, lotions and the like. For their preparation, bases and auxiliary substances conventionally used for such purposes can be used.

Other biologically active substances, for example vitamins, fruit acids, glycolic acid, etc., can be included in the composition of cosmetics containing the R-form of α-lipoic acid and / or its derivatives and / or its metabolic precursors.

Testing of cosmetics containing the R-form of α-lipoic acid, showed their high efficiency.

The following Examples merely illustrate the substance of the proposal and cannot be restrictive.

Example 1

To prepare 100 kg of cosmetic cream for aging skin, 46.06 kg of water is heated, with the addition of 1.5 kg of a 10% KOH solution, to 70 ° C. At the same time, an emulsion is prepared, for which 14.0 kg of stearic acid, 2 kg of cetyl stearyl alcohol, 1 kg of propylene glycol isostearate are mixed. The mixture is heated in a melting pot to a temperature of 70 ° C and stirred until a homogeneous mass. Water with a 10% KOH solution and an oil phase are poured into the reactor, water circulation and a homogenizer are turned on. After cooling the emulsion to 30 degrees, 1 kg of germaben II and a solution of the R-form of α-lipoic acid (5 kg of the R-form of α-lipoic acid in 29.44 kg of a 5% KOH solution) are introduced into the reactor. The contents are mixed until smooth. Adjust the pH to 6.8 with a 10% KOH solution.

Example 2

To prepare 100 kg of cosmetic gel, antistress is poured onto the surface of 28.65 kg of water, 0.6 kg of Carbopol Ultrez 10. 50 kg of water are poured into the reactor, the mixer is turned on and 1 kg of germaben II, 0.05 kg of EDTA, 2 kg of glycerin are added, 1.5 kg of butylene glycol include a low-speed mixer and 0.6 kg of PEG-40 hydrogenated castor oil is added. Stir until homogeneous and add a solution of Carbopol Ultrez 10, a solution of the R-form of α-lipoic acid (5 kg of the R-form of α-lipoic acid in 10 kg of ethyl alcohol). Stirred for 10 minutes and add 0.6 kg of a 10% KOH solution. The contents are mixed until smooth. Adjust the pH to 6.8 with a 10% KOH solution.

Claims (2)

1. A tool that improves the physiological state of skin cells, containing an acceptable carrier and an active principle, characterized in that as an active principle it contains the R-form of alpha-lipoic acid and / or its derivatives and / or its metabolic precursors. 2. The tool according to claim 1, characterized in that the content of the R-form of alpha-lipoic acid and / or its derivatives, and / or its metabolic precursors in it is from 0.1 to 10.0 wt.%.

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