WO1992000720A1

WO1992000720A1 - Agent and process for stimulating growth and regeneration of hair and nails

Info

Publication number: WO1992000720A1
Application number: PCT/EP1991/001297
Authority: WO
Inventors: Martin Schmidt-Achert
Original assignee: Schmidt Achert Martin
Priority date: 1990-07-12
Filing date: 1991-07-10
Publication date: 1992-01-23
Also published as: DE4022288A1

Abstract

The invention discloses an agent and a process for stimulating the growth and regeneration of hair and nails. An effective quantity of one or more amino acids or a mixture thereof selected from the group consisting of L-leucine, L-isoleucine and L-valine is administered.

Description

Means and methods for stimulating hair and nail growth and regeneration

The invention relates to an agent and a method for stimulating the growth and regeneration of hair in humans, which can also be used in veterinary medicine for pets or as an active ingredient for the quantitative promotion of hair growth in farm animals.

It is known that age-related and disease-related damage and manipulations such as washing, brushing, blow drying, coloring and shaping, which are common in daily life, can lead to premature hair loss and to inhibition of hair growth. There are different types of hair loss, most of which can be called "effluvium"; with visible hair loss one speaks of an "alopecia", in which baldness occurs mainly in men. Herd-shaped, diffuse and total alopecias are differentiated morphologically, the prognosis being differentiated into irreversible and reversible alopecias. Irreversible alopecia is characterized by the absence or destruction of the hair or the regression of the terminal hair to lanugo hair (balding, for example, due to pressure and tension or, as a rule, with alopezia androgenetica).

Both human and animal hair go through a life cycle which comprises three phases, firstly the anagen phase, secondly the catagen phase and thirdly the telogenic phase. The anagen phase represents a period of active hair growth and as far as the scalp hair is concerned, this period lasts 3 to 5 years. The catagen phase is a short transition phase between the anagen and telogen phases, which lasts only 1 to 2 weeks. The subsequent telogenic phase can also be referred to as the resting phase, in which all growth stops and the hair is rejected if necessary. Head hair in the telogenic phase has a very short life of about 3 to 4 months before it is rejected and new hair growth begins.

Under normal hair growth conditions, approximately 80% of the scalp hair is in the anagen phase, only 1% remains in the catagen phase and the rest in the telogen phase. With the occurrence of hair loss, as has been established, a larger proportion of the hair is in the telogenic phase, so that the proportion of actively growing hair in the anagen phase decreases.

Another result of alopecia is a large reduction in hair follicles. A person with hair loss has about 306 follicles per qcm, while a person with normal hair growth in the same age group has an average of 460 follicles per qcm. It is therefore assumed that balding is caused by a combination of different factors: regression of the terminal hair to Laugua hair, increasing number of hair in the te¬ logical phase, and loss of hair follicles. Other reasons which lead to hair loss include functional disorders of the thyroid gland, the adrenal cortex, the pancreas, metabolic disorders, infections, medications and poisoning.

For many years, scientists have been trying to slow down hair loss or stimulate hair growth even after balding with a variety of different developments.

A large number of agents and treatment methods, which relate both to external and / or internal use, were first tried out on animals and then also on humans. However, previous attempts have shown that the successes achieved in part were mostly bought with damage to health.

The agents for hair loss that have been commercially available up to now and the agents offered to stimulate hair growth are mostly built up from birch water, panthenol, zinc compounds, etc. Some of them also contain amino acids as active ingredients, such as S-carboxymethylcysteine, but this is very sensitive to oxidation and is easily dehydrated to the amino acid cystine.

There is also the possibility of promoting hair growth by additionally administering sulfur and sulfur-containing amino acids, in particular cysteine but also methionine.

Furthermore, it has long been known to temporarily increase hair growth by means of adrenal hormones, sex hormones or their antagonists. But because of hardly Avoidable serious side effects such treatments are rarely carried out and only under constant strict medical supervision. However, these are exclusively active substance applications in the form of medicaments, so that use as a hair growth and hair care product, cosmetic or food additive is out of the question.

From "The Lancet", May 7, 1988, 1016-1018 it is known to administer branched-chain amino acids to the patient orally for the treatment of muscle atrophy. These received daily doses of 12 g L-leucine, 8 g L-isoleucine and 6.4 g L-valine over a total period of 1 year. According to the literature site mentioned, this amino acid administration should stabilize the patient's neurological status, which should have a positive effect on the clinical picture. However, this has not yet been confirmed.

It is also known to apply the amino acid L-valine as a medicament for infusion solutions for IV administration to hepatic coma. In addition, solutions for the supply of amino acids in parenteral nutrition are used clinically.

The invention has for its object to provide a physiological hair restorer that is able to stimulate the growth and regeneration of the hair due to its physicochemical and biochemical properties, so that the quantitative hair growth and the quality of hair formation is improved, without being toxic Stress or danger to the organism arises. At the same time, the hair should be made more resistant to environmental influences and stresses. Finally, a method for stimulating hair growth and regeneration is to be made available.

These tasks are solved by the characterizing features of claims 1 and 11 respectively.

The invention is further developed by the features of the subclaims.

The invention is based on the surprising knowledge of the trophic effect of the branched-chain essential amino acids L-valine, L-isoleucine and L-leucine as active ingredients for a qualitative and quantitative promotion of hair growth in humans. By using the hair product according to the invention by daily treatment within a period of 12 months, the hair loss is stopped and the hair follicles are regenerated, so that the hair loss is slowed down and the hair growth is stimulated again. This affects "non-sexual" testosterone-independent hair such as scalp hair, eyebrows, eyelashes.

In addition, increased growth of the fingernails and toenails was observed.

In the present invention, an optimal amino acid mixture consisting of L-leucine, L-isoleucine and L-valine is used. It is known that the need for the other branched-chain amino acids increases due to an excess of a single branched-chain amino acid, so that a balanced mixture ratio is sought.

In this mixture, the ratio of the amino acids L-valine: L-isoleucine: L-leucine was chosen to be approximately equal to 1: 0.74 to 1.25: 1.86 to 1.875, a ratio in which the keratin build-up was in place and site is optimally stimulated. A ratio of L-valine: L-isoleucine: L-leucine = 1: 1.25: 1.875 is particularly favorable. This creates the biochemical precursor for the synthesis of keratin.

60% of the amino acids in portal blood that pass into the systemic circulation from the liver are branched-chain essential amino acids. These therefore play a disproportionately decisive role in the protein metabolism, one in particular, L-leucine, having a stimulatory effect on protein synthesis. Utilization of other amino acids is disturbed by a relative lack of branched chain amino acids.

Because the fact that the body carries out the synthesis of this keratin on the spot, it follows that the essential amino acids mentioned here must be present for these purposes.

In addition, the branched chain amino acids are important for the anabolic insulin effect in the muscle; Filling the protein stores in the muscle postprandially is a function of the uptake of branched chains Amino acids.

The use according to the invention of the amino acid mixture consisting of L-leucine, L-isoleucine and L-valine, which is suitable for oral and / or topical administration for the treatment of hair loss, is likely to continue - in addition to the regeneration of the hair follicles - The growth rate of the hair increased and the anagen phase of the hair cycle extended.

The novel agent according to the invention can be administered orally in the form of tablets, liquids, powders or capsules. In the tablets or capsules, the amino acid concentration of one or more or a mixture of the amino acids from the group consisting of L-leucine, L-isoleucine and L-valine is in the range between 0.1 and 25% by weight. In addition to the active constituents, the agent according to the invention can also contain the customary auxiliaries, carriers, diluents and additives.

Foodstuffs, in particular dietary foodstuffs, come into consideration as carriers. Dairy products such as yogurt, buttermilk, curd cheese, etc. are advantageously used as carriers. It is also possible to add the amino acid mixture according to the invention to dietary formulations. Depending on the application, the proportion of the respective amino acid may predominate and is not restricted to the above-mentioned ratio. The hair growth agent administered according to the invention contains, as an active ingredient, one or more or a mixture of highly purified amino acids from the group of branched-chain essential amino acids, consisting of L-leucine, L-isoleucine and L-valine. However, it is also possible to use pa-quality amino acids which have a lower degree of purity.

However, the agent according to the invention can also be formulated as a topical lotion, cream, ointment, conditioning preparation or as a shampoo. The amino acid concentration of one or more or of a mixture of the amino acids according to the invention in these formulations can be in the range between 0.1 and 25% by weight. The shampoos can contain the usual detergents or soaps and other substances. Additions of surfactants such as polyoxyethylene sorbitan oleate and lecithin to these topical formulations give advantageous effects. To improve blood circulation, ethyl nicotinic acid or its salts can also be added to the hair product.

In the case of therapeutic enteral use, the "recommended daily allowances" for essential amino acids are clearly exceeded (RDA about 0.2 to 0.4 mmol / kg body weight in adults; significantly higher in children); with a balanced diet, however, an upper limit for the intake of the essential amino acids is not known. The use of the active compounds according to the invention means that no side effects are to be expected and have not been observed with a physiologically adapted dosage.

Conceivable contraindications are congenital disorders of the valine and leucine metabolism (leucinosis) such as "branched chain disease" (maple syrup disease); A reduction in the amino acid intake with a changed ratio of the branched-chain to aromatic amino acids is indicated in the case of hepatic encephalopathy, renal insufficiency and disorders in urea synthesis.

The use of the agent according to the invention is not only limited to humans, but can also be used in veterinary medicine for pets and can be used to support the physiological hair growth in livestock by nutritional use as a feed additive. As described above, the agent according to the invention is used in the livestock, preferably as a feed additive (nutritive) by admixing with the feed or by producing feed enriched with the agent, for example by pelleting. Depending on the species of animal, the application dose can be in the range from about 0.2 to 0.4 mol of the amino acid mixture according to the invention / kg of body weight. Depending on the diet of the respective animal species, the dose is administered either continuously or discontinuously. The invention will now be described in more detail by means of examples.

Example 1:

8 to 10 patients were treated with a daily dose of 12 g L-leucine, 8 g L-isoleucine, 6.4 g L-valine each over a period of 12 months, with the patients taking this daily dose orally in four divided doses had. After 6 to 12 months there was a pronounced promotion of hair formation and an increased quantitative hair growth, as well as a growth of the nails.

Example 2:

The powdery amino acid mixture administered according to Example 1 can also be administered in the form of tablets which have the following composition:

Active components:

L-leucine, L-isoleucine, L-valine 17.86% by weight

Lactose 37.14% by weight

Cereal starch 14.28% by weight

Microcrystalline cellulose 28.57% by weight

Talc 1.79% by weight

Magnesium stearate 0.36% by weight The active ingredients were mixed with lactose and granulated using a cereal starch paste. The remaining constituents listed above were then mixed in and the resulting mass was pressed in tablet form. The tablets produced in this way can be provided with a water-soluble or water-swellable lacquer layer.

Such tablets can be administered orally to the patient as described in Example 1 so that the daily dose listed in Example 1 of 12 g L-leucine, 8 g L-isoleucine and 6.4 L-valine is achieved.

Example 3:

The amino acid mixture according to the invention can also be used as a food substitute to promote hair formation. For this purpose, 3.0 g of L-leucine, 2.0 g of L-isoleucine and 1.6 g of L-valine are added to 93.4 g of yoghurt and mixed, so that a homogeneous mixture is formed. Such a dose was administered to 8 to 10 patients four times a day over a period of 30 days. The total treatment period was 12 months, after which the patients showed significantly increased, quantitative hair and nail growth.

Example 4:

The effects described in Example 1 can also be achieved with a daily dose, each consisting of 10.86 g L-leucine, 4.35 g L-isoleucine and 5.82 g L-valine and is administered orally in three divided doses.

Example 5:

The daily dose given in Example 4 can also be administered in the form of tablets or coated tablets according to Example 2.

Example 6

The daily dose given in Example 4 can also be used in the form of a food substitute according to Example 3. So z. B. 3.62 g of L-leucine, 1.45 g of L-isoleucine and 1.94 g of L-valine are added to 93 g of yoghurt and mixed so that a homogeneous mixture is formed. This mixture is administered analogously to Example 3, but only three times a day.

Claims

Claims:

1. Agent for stimulating the growth and regeneration of hair and nails, characterized in that it contains one or more of the amino acids L-leucine, L-isole leucine, L-valine.

2. Composition according to claim 1, characterized in that it contains a mixture of the amino acids L-leucine, L-isoleucine and L-valine.

3. Composition according to claim 2, characterized in that the proportion of an amino acid predominates in the mixture depending on the application.

4. Composition according to claims 2 and 3, characterized in that the ratio of the amino acids L-valine to L-isoleucine to L-leucine in the mixture is approximately equal to 1: 0.74 to 1.25: 1.86 to 1.875 .

5. Composition according to claims 1 to 4, characterized in that it contains the usual auxiliaries, carriers, diluents and additives in addition to the active ingredients.

6. Composition according to claims 1 to 5, characterized in that it is for oral administration as a tablet, liquid speed, powder or capsule.

7. Composition according to claim 6, characterized in that the amino acid concentration of the preparations for oral administration is in the range between 0.1 and 25 wt .-%.

8. Composition according to claims 1 to 5, characterized in that it is formulated as a topical lotion, cream, ointment, conditioning preparation or as a shampoo.

9. Composition according to claim 8, characterized in that the amino acid concentration of the formulations is in the range between 0.1 and 25 wt .-%.

10. A composition according to claim 5, characterized in that foods, in particular dietetic foods, are used as carriers.

11. A method of stimulating the growth and regeneration of hair and nails, characterized in that an effective amount of one according to any of the

Claims 1 to 10 designated agent is administered.

12. The method according to claim 11, characterized in that the administration orally in the form of tablets, fluids. liquids, powders or capsules and / or topically by adding to hair tonics, shampoos, cosmetics or care products or to the bath water.

13. The method according to any one of claims 11 or 12, characterized in that an amino acid mixture is administered orally in a daily dose of 12 g L-leucine, 8 g L-isoleucine and 6.4 g L-valine.

14. The method according to any one of claims 11 or 12, characterized in that an amino acid mixture is administered orally ^' in a daily dose of about 10.86 g L-leucine, 4.35 g L-isoleucine and 5.82 g L-valine.