DE202005021598U1 - Dermatological formulation - Google Patents

Abstract

dermatological Formulation containing an active substance complex comprising N-biotinyl-Gly-His-Lys, oleanolic acid, Apigenin, diosgenin, trigonelline and L-arginine.

Description

The The invention relates to a formulation, especially for care of skin, nails and hair, for promotion of hair growth, to delay hair loss and support in hair transplants, is suitable.

hair loss can be attributed to a variety of factors. Some of these factors are stress, disorders thyroid function and taking medications. Another factor is, besides the inflammatory Appearances and infections of the scalp, for example, by Bacteria or fungi are caused, the hormone-induced failure. This is mostly due to the formation of dihydrotestosterone (DHT) conditioned and is also referred to as hereditary hair loss. An increased Concentration of DHT in the hair follicles leads to an increased mitotic rate and to a shortening the growth of the hair. The hair and the follicle become at each Hair loss thinner or smaller, until finally only small Lanugohaare be produced. Usually the hair growth phase is hair two to six years, while in pre-dawned Fall to about a year. Overall, a hair can only be 10 to 12 regrow, so it comes in this way premature to the final failure of the hair. In this phase, the blood supply to the hair root by constriction cut off with connective tissue and the hair follicle disappears after the failure of the hair.

in addition come factors like malnutrition The hair roots, which are usually due to poor circulation returns as well as the poor anchoring of the hair in the scalp. Often enough comes a variety of factors that shape the overall picture. to Slowing down and avoiding hair loss or stimulation In hair growth, a variety of remedies have been developed.

The most means to combat However, hair loss is due to the topical application of a hair loss Variety of active ingredients. These include formulations that z. B. amino acids and their derivatives, vitamin supplements and also a number of circulation-enhancing and nutrient-supplying Contain substances that are topically applied or massaged.

hair loss however, is usually a drag on for long periods of time Process to which many factors contribute. A possible cause of hair loss and restricted Hair growth can, as already stated, a shortage of Hair follicles with necessary nutrients be attributed, for example, to a poor circulation can. A limitation the metabolic balance of the hair follicles and thus the hair leads then to a fault intracellular and intercellular signaling pathways. The ongoing shortage the hair with nutrients as well as the disorder the signaling pathways requires a long-lasting shortage Death of hair follicles.

by virtue of The above factors therefore have a need for a formulation for peroral application, which is able to simultaneously several or all of these factors are positive in the sense of preventive support, care and / or to promote Hair growth and delay to contribute to the hair loss and regularly if necessary on a longer Period can be taken.

These Task is solved with a formulation containing an active ingredient complex including wheat germ meal, fenugreek seed extract and millet seed extract in a physiologically effective amount.

Further There is a need for an active system that favors the hair follicles and Hair applied perorally as well as topically supplied with nutrients, anti-inflammatory works and in both the qualitative and the quantitative Composition is optimally matched.

These Task is solved by an active system, the peroral invention Formulation together with a dermatological formulation which an active ingredient complex of N-biotinyl-Gly-His-Lys, apigenin, oleanolic acid, L-arginine, Diosgenin and Trigonelline includes.

This Effective system contributes when used together with the oral formulation and the dermatological Formulation in particular to positively influence the preventive support, care and / or to promote Hair growth and delay hair loss. The active system can also be used together over a longer period of time become.

Preferably, the peroral formulation according to the invention contains the wheat germ meal, the Bocks horn clover seed extract and the millet seed extract in the active ingredient complex in a ratio of 0.75-1.25: 1.75-2.25: 3.75-4.25 based on the respective weight of the components. Particularly preferred is a ratio of 1: 2: 4 with a fluctuation range of ± 0.1.

Of the The aforementioned active ingredient complex is preferably high-dose in the Formulation introduced. High concentration is a concentration of at least 20% by weight, for example up to 70% by weight elevated can be, in particular 30 wt .-% to 50 wt .-%, preferably in order 40% by weight understood, the formulation by other active ingredients, Additives and / or auxiliaries to 100 wt .-% is added.

The inventive formulation contains in the simplest variant, the aforementioned active substance complex in the specified quantities. Other basic, auxiliary and active ingredients can be added if necessary.

Of the Active substance complex is characterized by the fact that it is made of all-natural Plant extracts or plant constituents, which naturally the necessary nutrients and active ingredients. The wheat germ meal is rich in high quality Protein. The semiessentielle amino acid Arginine is in increased concentration, up to 2500 mg per 100 g of wheat germ. This semiessentielle amino acid will for the Protein structure needed and therefore has a positive effect on hair growth. Moreover, in the wheat germ also folic acid contain a central role in cell growth and cell renewal plays. As averages for the ingredients are based on 100% - 30% protein, 6% germ oil, 45.5% Carbohydrates, 9.5 dietary fiber, 4.5% minerals and 5.0% moisture - stated.

Of the Millet seed extract is a natural one Source for Silica. Contains millet seed extract a high proportion of this acid, the for the construction of hair and nails of the human body is essential. silica is important for the elasticity and firmness of hair. Furthermore It is an important component of keratin, one of the most important protein components involved in hair restoration. Usual millet seed extract preparations are diluted to 10: 1 and contain about 11.25% by weight of silica. The millet seed extract as well as siliceous Excipients are added to the tablet formulation until Silica content per tablet is from 20 to 30 mg, in particular 20 to 25 mg. One Content of, for example, 23.2 mg of silica per tablet a silicon content of 10.3 mg.

The particular properties of fenugreek seed extract from his composition. The seeds of fenugreek contain to about 28% mucilages (glycomanans), are partially in the Literature up to 45% indicated. These glycomans are predominantly from galactomanans. 0.13% is trigonelline, a nicotinic acid derivative, which is converted into nicotinamide (vitamin PP). In The literature is the amino acid composition of the protein in the seeds of fenugreek (g each 16 g N) as follows indicated: alanine 4; Arginine 9.2; Aspartic acid 10.9; Cystine n.b; histidine 2.0; Isoleucine, 4,5; Leucine 6,8; Lysine 6.0; Proline 4.6; serine; 5.2; Threonine 3.0; Tryptophan 1.6. Other important ingredients of the Fenugreek seeds are the vitamin C, which is up to 200 mg per 100 g may be contained, vitamin E and sapogenin glycosides, Flavonoids and a high content of essential oils.

Of the active ingredient complex according to the invention is in its nutrient and mineral composition optimally to the needs of hair, skin and nails Voted. The particular advantage of the active substance complex lies in its combination of nutrient and minerals suppliers and the presentation of these nutrient and Minerals in the form of their natural Sources. The aforementioned nutrient and minerals are special because of their natural occurrence bioavailable and compatible. Need something like that some of these natural nutrients, Mineral and active ingredients provide improved stabilization to one Decomposition and / or reduced release of naturally present nutrients, Active ingredients and / or minerals after prolonged storage of the formulation to prevent.

In addition to The above-mentioned compounds, the inventive formulation further Active ingredients and auxiliaries, in particular an influence to have hair growth and / or to adjust the properties contribute to the formulation.

An active ingredient that supports the moisture retention capacity of the skin and the scalp, ie acts as a moisturizing factor, is panthenol. A derivative of panthenol is, for example, DL-ethyl panthenol, which is metabolized to pantothenic acid and forms an important building block of coenzyme A. Furthermore, pantothenic acid is involved in the metabolic process and plays a central role in hair growth. Pantothenic acid promotes hair growth and ensures the pigmentation of the hair. Dexpanthenol, also known as panthenol or ProVitamin 5. In addition to panthenol, derivatives of panthenol, as the pantothenic acid, panthenyl ethyl ether, panthenyl ethyl ether, Panthenyltriacetat other panthenol analogues, especially physiologically acceptable salts, such as alkaline earth or alkali metal salts of pantothenic acid in the formulation are used.

Prefers Calcium pantothenate is used. The calcium pantothenate is in the skin to pantothenic acid metabolized and is, as stated above, an important building block coenzyme A. The derivatives of panthenol, in particular the salts, most preferably the calcium pantothenate is in an amount of 0.5 to 5 wt .-%, in particular 1 to 2 wt .-% in the formulation.

One Another active substance is niacin, which is also known as nicotinamide or Vitamin PP is known. Related to the pure niacin it is with 0.5 to 5 wt .-%, in particular with 1 to 2 wt .-% in the formulation in front. When using niacin preparations containing about 33% by weight of niacin will be 1 to 10% by weight, especially 2 to 5 wt .-% of the preparation used. Niacin causes an expansion of the blood vessels, so that an improved supply of specific nutrients through improved circulation he follows.

When further active, nutri- and mineral supplements the following compounds are the formulation in view of needs hair, nails and skin.

The vitamin B ₁₂ is based on the pure active ingredient with 1 × 10 ^-4 to 2 × 10 ^-1 wt .-%, in particular with 1 × 10 ^-4 to 5 × 10 ^-4 wt .-%. When using depleted vitamin B ₁₂ preparations with, for example, a vitamin B ₁₂ content of 0.1%, this composition is introduced at 0.1 to 1.0 wt .-% in the formulation. Vitamin B ₁₂ is necessary for hair health and hair regrowth.

Behind The collective term vitamin E hides tocopherols. vitamin E stands for derivatives of 2-methyl-6-hydroxychromans with different numbers of methyl radicals in the ring system and isoprenic side chain. The tocopherols have the Property to easily oxidize and thereby lose their biological Function. In the formulation, the vitamin E, in particular as Vitamin E acetate introduced. The vitamin E promotes blood circulation and prevents blood clotting and lumps in the blood. The improved Circulation causes improved nutrient transport in the scalp. The vitamin E and its derivatives are in the form of the pure active ingredient with 0.05 to 5 wt .-%, in particular 0.5 to 1.5 wt .-% in the formulation brought in. In the form of a 50% composition is the vitamin E-containing composition, for example with vitamin E acetate too 0.5 to 2.5 wt .-% used.

Of the Active ingredient biotin (vitamin H) is involved in protein metabolism and will build up the protein structure the hair needed. Furthermore, biotin accelerates the development of keratinocytes, the keratin-forming cells. Keratin is a horny and a Basic building block of the hair. The biotin is based on the pure active ingredient to 0.001 to 0.5 wt .-%, in particular 0.01 to 0.05 wt .-% in of the formulation. Using an example 1% biotin-containing composition will be 1 to 5 wt .-%, in particular 2 to 3 wt .-% of this composition introduced into the formulation.

Folic acid is additionally added to the folic acid already contained in the fenugreek seed extract in an amount of 0.001 to 0.1% by weight, in particular 0.01 to 0.05% by weight, relative to the pure active ingredient of the formulation. The body needs folic acid for cell division and wound healing. Together with the vitamin B ₁₂ , the folic acid ensures a rapid development of the red blood cells and thus indirectly ensures the oxygen supply to the body and thus the scalp and the hair follicles.

zinc is an essential trace element and involved in the formation of keratin and involved in the formation and cross-linking of collagen. Collagen anchors, on the one hand, the hair in the skin and is also responsible for the hair structure significant. A zinc deficiency presses For example, in the form of circular hair loss (Alopecia Areata). Preferably, the zinc is as slightly soluble physiologically compatible Salt, for example as zinc chloride or zinc citrate, in particular introduced as zinc citrate trihydrate in the formulation. The zinc salt, in particular, the zinc citrate trihydrate is used in an amount of 0.01 to 3 wt .-%, in particular 0.5 to 1.5 wt .-% added. At 100 % By weight is added by addition of the active substance complex and / or other auxiliaries set.

The the aforesaid selection of nutrient, Active ingredients and minerals are specially tailored to the nutritional needs of hair, skin and nails, especially for the care of skin, nails and hair, for promotion of hair growth, to delay hair loss and support tuned for hair transplants when given orally.

Preferably is the formulation of the invention in the form of an orally administrable tablet. Nevertheless, you can they are also prepared as a drinkable tablet, what the formulation an elevated one Contains proportion of disintegrant.

The inventive formulation contains preferably by weight, the active ingredient complex comprising wheat germ meal 0.75 to 1.25% by weight to fenugreek seed extract 1.75 to 2.25 Wt .-% and millet seed extract to 3.75 to 4.25 wt .-% in the ratio, respectively based on their weight. The active substance complex itself is preferred with 30 wt .-% to 50 wt .-%, in particular about 40 wt .-% based used on 100% of the formulation.

to Stabilization of the active substance complex are adjuvants with pronounced swelling capacity used. Of particular note here are the ones present in fenugreek seeds Galactomanans, which over a very good swelling capacity feature. additionally microcrystalline cellulose was incorporated into the formulation. The galactomanans found in fenugreek seed extract act at the later dissolution of the Tablet in a liquid as a gelling agent. By the hydration of galactomanans takes place at the interface Liquid / tablet a gelation, which forms a gel barrier. Initially disabled this the contact of the drugs enclosed by it with the Dissolving liquid. As time progresses, the volume of the tablet body increases Outside moistened to the inside, with a total of a swollen matrix formed. This releases the active ingredients and nutrients both from the entrance of the liquid in the system, as well as by the diffusion rate of the active ingredients through the gel layer dependent. The release of the active ingredients and nutrients takes place during the body passage now by diffusion and removal of the outer layers by mechanical Abrasion. By using natural Gelling agent, the galactomanane will get a tablet containing a uniform, of pH and enzyme ratios largely independent Liberation of several hours. As fillers or extenders are conventional auxiliaries like corn, potato and wheat starch as well as various lactoses, such as lactose monohydrate or lactose derivatives into consideration.

By the stabilization according to the invention the active ingredient complex and / or the additional active ingredients and nutrients is also after a three-month storage of the formulation at 40 ° C and 75% relative humidity almost unchanged release, in particular a stabilization of individual and / or all active, nutrient and Minerals achieved.

The galactomanans naturally present in fenugreek seeds stabilize not only the active ingredient complex as such before decomposition but also the temperature-sensitive and in some cases moisture-sensitive nutrients and vitamins such as vitamin B ₁₂ , niacin, vitamin E and / or biotin due to the high concentration of fenugreek seed extract.

The mentioned in the beginning, in particular on the peroral formulation, dermatological formulation preferably contains a drug complex by weight comprising N-biotinyl-Gly-His-Lys, oleanolic acid, apigenin, Diosgenin, trigonelline and L-arginine 0.1 to 5.0%, ethanol 5 to 50%, isopropanol 5.5 to 10.0% an acid or base for adjustment a pH in the range of 6.8 to 7.8 and water ad 100%.

Of the Content of diosgenin and / or trigonelline varies in the extract, conditionally through the natural Origin of the active ingredients strong. In the extracts is usually a concentration of at least 0.3 g / L demonstrated. An appropriate one Extract is preferably from 1 to 5, preferably 2% by weight of a formulation added. At a level of about 2% by weight, a content of diosgenin would be and / or trigonelline of at least 0.0006% by weight. Of the Concentration range of trigonelline and diosgenin is preferably in the range of 0.00015 to 0.003 wt% in the formulation.

The Composition according to the invention contains in the simplest embodiment the abovementioned constituents in the stated amounts. Other ingredients can be present. The difference to 100 wt .-% consists of water, in usually demineralized water. All weights are in Wt .-%.

The N-Biotinyl-Gly-His-Lys is a biotinyl tripeptide whose use has already been described in hair lotions. The biotinyl tripeptide is a vitaminizing peptide that is capable of firming the anchoring of hair in the scalp, in particular by its influence on follicle and cell growth. Apigenin is a flavonoid that occurs naturally in citrus fruits, but also in the sharply. Apigenin promotes the circulation of the scalp and especially the hair root. This will provide the nutrient supply the hair root improves and thereby promotes hair growth. Oleanolic acid, as a natural component in olive tree leaves, is a triterpene-type, which can penetrate the scalp and counteract the formation of the hydrotestosterone responsible for hereditary alopecia. These three agents are usually present at significantly less than 1%, based on the weight of the formulation. In fact, the effectiveness of the active ingredients is generally from 1 to 1000 ppm, in particular from 2 to 500 ppm. The L-arginine is preferably present at a level of from 0.1 to 5.0%, especially 2.0 to 4.0, especially 3.0% in the formulation. L-arginine is an essential amino acid essential for hair growth. In addition, L-arginine is a precursor to nitric oxide NO, a messenger substance in cell metabolism that can stimulate hair growth. Also, L-arginine contributes to the secretion of growth hormones.

diosgenin is obtained by hydrolysis from steroidal saponoside. The steroidal Saponoside has a hypoglycemic Effectiveness and inhibits the proliferation of pathogenic bacteria. Trigonelline is an alkaloid. Both the diosgenin and the Trigonellin are included in the extract Trigonella foenom-Graecum. Other care and nutrients, such as lipids (oleic acid, linoleic acid), phytosterols, Proteins, lecithins, phytin (calcium and magnesium ionophosphates) and other alkaloids are included in the extract and are positive combined with the active ingredient complex in the dermatological formulation.

Of the Extract from Trigonella Foenom-Graecum has been used for a long time Mature skin uses and prevents skin aging. Furthermore acts Extract stimulating and repairing on cellular metabolism. He practices one cell-supporting influence and supports an intercellular exchange.

Also the extract is anti-inflammatory, Regenerates the skin and is an emollient that soothes the skin. This effect is due to the high content of mucus, lecithin and recycled organically bound phosphorus. The extract comprising Diosgenin and trigonelline are preferred in the range of 1 to 5%, in particular 1 to 3, preferably 2 wt .-% in the dermatological Formulation used. The content of diosgenin as well as trigonelline is in the range of over 0.3 g / L. Both diosgenin and trigonelline are preferred with 0.00015 to 0.003% or 0.003 to 0.012 wt .-%, in particular at 0.0006% by weight, each in the dermatological formulation contain.

Of the Active substance complex comprises an active ingredient concentrate of N-biotinyl-Gly-His-Lys, oleanolic acid, apigenin. The content of the active substance complex consisting of the above concentrate, L-arginine, diosgenin and trigonelline suitably with 5 to 15 wt .-% in the dermatological formulation before, preferably with 8 to 12 wt .-%, wherein the formulation by other active, nutrients, minerals and / or adjuvants is supplemented to 100 wt .-%. The active ingredient concentrate from N-Biotinyl-Gly-His-Lys, oleanolic acid and apigenin contains the listed active ingredients in the following concentrations - 200 ppm N-Biotinyl-Gly-His-Lys, 300 ppm oleanolic acid and 500 ppm apigenin - and is from 1 to 10, preferably from 2 to 6, in particular to 5 wt .-% included in the formulation.

The dermatological formulation preferably contains by weight N-biotinyl-Gly-His-Lys 5 to 100 ppm, oleanolic acid 2 to 300 ppm, each preferably 4 to 100 ppm; Apigenin 2 to 500 ppm, especially 20 to 100 ppm and 0.00015 to 0.003 wt .-% or 0.003 to 0.012 wt .-%, in particular 0.0006 wt .-% diosgenin and / or trigonelline as well as the usual ones Auxiliaries of a liquid dermatological formulation.

The invention is explained in more detail by the following formulation examples. Example 1: Calcium pantothenate 11,900 g Niacin 33.33% 31,400 g Vitamin B12 01,% 1,650 g Vitamin E acetate 50% 17.290 g Biotin 1% 25,820 g folic acid 0.290 g Zinc citrate trihydrate 8.450 g Wheat germ flour 50,000 g Fenugreek Seed Extract (FENULIEFE) 100,000 g Millet Seed Extract 10: 1 200,000 g silica 10.606 g magnesium stearate 5,800 g stearic acid 9,000 g Microcrystalline cellulose 135.300 g lactose 278,500 g hydroxypropyl 14,000 g Example 2: Calcium pantothenate 11,900 g Niacin 33.33% 31,400 g Vitamin B ₁₂ 01,% 1,650 g Vitamin E acetate 50% 17.290 g Biotin 1% 25,820 g folic acid 0.290 g Zinc citrate trihydrate 8.450 g Wheat germ flour 37.500 g Fenugreek Seed Extract (FENULIEFE) 125,000 g Millet Seed Extract 10: 1 150,000 g silica 10.606 g magnesium stearate 5,800 g stearic acid 9,000 g Microcrystalline cellulose 155.300 g lactose 296,500 g hydroxypropyl 14,000 g Example 3: Calcium pantothenate 11,900 g Niacin 33.33% 31,400 g Vitamin B12 01,% 1,650 g Vitamin E acetate 50% 17.290 g Biotin 1% 25,820 g folic acid 0.290 g Zinc citrate trihydrate 8.450 g Wheat germ flour 62.500 g Fenugreek Seed Extract (FENULIEFE) 125,000 g Millet Seed Extract 10: 1 250,000 g silica 10.606 g magnesium stearate 5,800 g stearic acid 9,000 g Microcrystalline cellulose 130,000 g lactose 296,000 g hydroxypropyl 14,000 g

In In all three examples, the batch size is based on 900 g. The pill is preferred twice a day in the morning and evening before the Meals are taken with plenty of water.

Example 4:

• 1. denaturierter Alkohol 25%
• 2. Isopropanol 3,0%
• 3. Wirkstoffkomplex bestehend zu 5% aus einem Wirkstoffkonzentrat, 3% L-Arginin und 2% Trigonella Foenom-Graecum
• 4. Zitronensäure 1,2% ggf. Farbstoffe, Geruchsstoffe sowie weitere Hilfsstoffe
• 5. Wasser ad 100%

For the dermatological formulation, the following ingredients were mixed by weight:

• 1. denatured alcohol 25%
• 2. isopropanol 3.0%
• 3. Active substance complex consisting of 5% of an active substance concentrate, 3% L-arginine and 2% Trigonella Foenom-Graecum
• 4. Citric acid 1.2% optionally dyes, odors and other auxiliaries
• 5. Water ad 100%

The Contains active ingredient concentrate at 5% 200 ppm biotinyl tripeptide, 300 ppm oleanolic acid and 500 ppm apigenin combined with butylene glycol, PPG-26-buteth-26 and PEG-40 hydrogenated castor oil, 1% each in a mixture of water, alcohol and isopropyl alcohol to 100 g of concentrate.

Of the Extract Trigonella Foenom-Graecum contains at least 0.3 g / L of Diosgenin and at least 0.3 g / L of trigonelline and at least 5 g / L of sugars. It is understood that the said extract by the type of processing, by dilution or concentration significantly fluctuating levels of diosgenin and may have trigonelline. Depending on the specification of the manufacturer the extract is therefore added so that in each case 0.00015 to 0.003% or 0.003 to 0.012, preferably about 0.0006 wt .-% of diosgenin and Trigonellin are included in the dermatological formulation.

Example 5:

One Kit in the form of an active system includes a peroral formulation according to example 2 and a dermatological formulation according to Example 4.

Claims (12)

Dermatological formulation containing a Active substance complex comprising N-biotinyl-Gly-His-Lys, oleanolic acid, apigenin, Diosgenin, trigonelline and L-arginine. Formulation according to claim 1, characterized in that that the dermatological formulation after a drug complex after Weight comprising N-biotinyl-Gly-His-Lys, oleanolic acid, apigenin, Diosgenin, trigonelline and L-arginine 0.1 to 5.0%, ethanol 5 to 50%, isopropanol 5.5 to 10.0%, one Acid or Base for adjusting a pH in the range of 6.8 to 7.8 and water ad 100%. Formulation according to Claim 1 or 2, characterized that they contain diosgenin and / or trigonelline with a content of 0.00015 to 0.003 wt .-% contains. Formulation according to one of claims 1 or 3, characterized that by weight N-biotinyl-Gly-His-Lys to 5 to 100 ppm, oleanolic acid to 2 to 300 ppm and apigenin to 2 to 500 ppm. Formulation according to one of Claims 1 to 4, characterized that the active substance complex with 5 to 15% in the dermatological Formulation is present and the formulation by further active, Nutrients, minerals and / or adjuvants is supplemented to 100 wt .-%. Kit in the form of an active system consisting of a dermatological formulation according to one of claims 1 to 5 and a peroral formulation comprising a drug complex Wheat germ meal, fenugreek seed extract and millet seed extract in a physiologically effective amount. Kit according to claim 6, characterized in that the active ingredient complex of the peroral formulation the wheat germ meal, the fenugreek seed extract and the millet seed extract in the ratio of 0.75-1.25: 1.75-2.25: 3.75-4.25 on her weight. Kit according to claim 6 or 7, characterized that the active substance complex of the peroral formulation with 30-50 wt .-% is present in the formulation and the formulation by further Active, nutrient, Minerals and / or excipients to 100 wt .-% is added. Kit according to one of claims 6 to 8, characterized in that the peroral formatting as white tere active ingredients, nutrients and minerals pantothenol and / or a derivative of pantothenol, a salt of pantothenic acid with 0.5 to 5 wt .-%; Niacin at 0.5 to 5% by weight; Vitamin B ₁₂ at 1 × 10 ^-4 - 2 × 10 ^-1 % by weight; Vitamin E and / or derivatives of Vitamin E at 0.05 to 5 wt .-%; Biotin at 0.001 to 0.5% by weight; Folic acid with 0.001 to 0.1 wt .-% and / or zinc salts with 0.01 to 3 wt .-% in addition to the active ingredient complex, which is supplemented with excipients to 100 wt .-%. Kit according to one of claims 6 to 8, characterized in that the peroral formulation as further active ingredients, nutrients and minerals calcium pantothenate with 1 to 2 wt .-%; a 33.3% niacin preparation at 1 to 10 wt%; a 0.1% vitamin B ₁₂ preparation at 0.1 to 1.0% by weight; a 50% vitamin E or vitamin E acetate preparation at 0.5 to 2.5% by weight; a 1% biotin preparation to 1.0 to 5.0 wt .-% folic acid at 0.001 to 0.1 wt .-% and / or a zinc chloride, zinc citrate, in particular zinc citrate trihydrate to 0.01 to 3 wt. -% in addition to the active ingredient complex, which is supplemented with excipients to 100 wt .-%. Kit according to one of claims 6 to 10, characterized that the peroral formulation is a consistent release of the active substance complex after a three-month storage at 40 ° C and 75% relative humidity has. Kit according to one of claims 6 to 11, characterized that the peroral formulation is a nearly constant release of all active substances after three months storage at 40 ° C and 75% relative humidity has.