FR2612776A1 - Process and composition for tanning in two phases - Google Patents

Abstract

Process and composition for skin tanning in two phases, a supply of reconstituted pigment and a transfer of melanogenesis constituents.

Description

 The present invention relates to a tanning process and compositions for carrying out this process and processes for their manufacture.

 The prior art knows innumerable methods and tanning compositions but we come up against a lot of problems because even the natural tan raises due to the particular harmful nature of certain wavelengths of solar radiation, mainly in the ultraviolet.

 On the other hand, even products of natural origin, such as carotene or psoralens, which exist in many fruits and vegetables have disadvantages; some because of the inesthesic colorations that they cause the others suspected of harmfulness (up to being considered, for some, as carcinogens).

 Many researches are therefore oriented towards very different solutions based in particular on interventions in melanogenesis.

 Here we must recall the principles of this natural melanogenesis.

Melanins are brown or black pigments found not only in the cells of the melanocytic system of the skin, but also in the neurons of the central nervous system or the adrenal medulla. These melanins are polymers of rather complex structure, still rather poorly known, but of high molecular weight.

They are insoluble in most solvents and have a high chemical inertness.

In the melanocyte cell occur a number of reactions essentially from tyrosine

This is obtained in particular by hydroxylation of phenylalanine.

 Phenylalanine is therefore a precursor of tyrosine allowing from a raw material external to the cell to create this essential component tyrosine in the production of melanin in the mucosomes. It is at the level of pre-melanosomes contained in the cell that the various syntheses leading to melanin begin.

Tyrosine is hydroxylated to dihydrophenylalanine (DOPA) in the presence of tyrosinase and oxygen.

This irreversible hydroxylation can also take place in the presence of peroxidase and / or Cu ions
Tyrosinase also catalyzes the oxidation of DOPA to DOPA-quinone in the presence of a reducing agent such as ascorbic acid and / or Cu ion

 It will be recalled that the tyrosinase enzyme is a phenoloxidase-type complexproproprotein, specific for tyrosinase and DOPA.

 The Cu ++ ion plays an essential role in the action of tyrosinase, which can be inhibited in particular by compounds with a thiol group such as glutathione, the concentration of which varies from one race to another (it is therefore lower among blacks only in whites). It has been noted above that peroxidase can also oxidize tyrosine to DOPA.

 The other melanogenesis reactions take place in the absence of enzyme or catalyst.

The DOPA quinone is cyclized to leuco DOPA chromium, which is then oxidized to DOPA chromium (that is to say, to the quinone corresponding to leuco DOPA chromium

et qui est associé à une structure protéique (mélanoprotéine).DOPA chromium is a red compound with maximum absconds at 305 and 475
The three compounds of reactions (5) above can give melanin by polymerization and / or polycondensation, melanin being a polymer whose linkon is of the form

and which is associated with a protein structure (melanoprotein).

DOPA chromium can be decarboxylated to give 5-6-dihydroxyindole which oxidizes to indole 5-6 quinone, yellow compound (with absoption maxima at 300 and 450

 5-6-dihydroxynidole can also be polymerized to melanin. Melanin absorbs radiation in a wide range from 200 to 2,400 m without really sharp maxima.

Pheomelanins, which are yellow and red pigments can also derive from tyrosine from DOPA quinone and / or
DOPA chromium and / or 5-6 dihydroxy indole
Melanosomes consisting mainly of melanin migrate to the dendrites that the melanocyte presents to cross the wall and penetrate the keratinocytes thus colored.

 In the prior art, it has been proposed to use tyrosine associated with amino acids to give a natural peptide. Thus the hardly soluble tyrosine gives rise to this peptide which has the advantage of being soluble, the amino acids synergistically intervening in the melanocyte to obtain pigmentation. However, experience has shown that these compositions have the serious disadvantage of increasing the mitotic index and may be suspected of promoting carcinogenesis.

 The present invention aims to provide both a fast tanning and durable without the disadvantages encountered in the prior art.

 To do this, the process according to the invention essentially comprises two successive phases by firstly ensuring artificial pigmentation by penetration of the components into the superficial layer of the skin, and their reaction with the amino acids of the superficial layers of the skin. epidermis, and then relaying by a natural pigmentation induced during the first phase, the two phases being provided preferably with a composition in a particular dosage form.

 To do this, the invention uses inter alia phenylalanine (or its derivatives or substituted) which is as we have seen a precursor of tyrosine, optionally associated with tyrosine itself and aspartic acid or its derivatives or substituted; but phenylalanine, tyrosine and aspartic acid are not water soluble; or the implementation of processes to obtain the compositions according to the invention through the intervention of an alkali metal or alkaline earth in the basic state or aspartate.

 Aspartic acid increases cellular respiration and oxidative phosphorylation. In addition, and experience has demonstrated remarkably, this acid and its derivatives promote the metabolism of certain components according to the invention and in particular amino acids.

 According to a first example of a process, tyrosine and phenylalanine in hydrochloric acid form are brought into the presence of sodium aspartate; it results in a sodium chelation, which makes the whole water-soluble.

 According to a second variant, in a sodium hydroxide solution, tyrosine and phenylalanine are dissolved and the aspartic acid is gradually added. The set has an alkaline pH. With the aid of a pH regulator, a stable microcolloid is obtained, based on a mixed aspartate of tyrosine and phenylalanine. These compositions are associated with escin which, a known anti-inflammatory and vasodilator, improves the permeability of the cell membrane and will facilitate the penetration of the compositions.

Cu (OH) 2 or a Cu salt is also added to create the excess of
Cu ++ whose utility has been emphasized above, for example gluconate.

 It is also possible, according to a preferred embodiment of the invention, to protect the transformations brought about by the compositions in accordance with the invention, and in particular the action of tyrosinase, by means of collagen hydrolyzate which presents in addition the advantage of maintaining the hydration of the skin, to promote the transit of the compositions, to protect the tyrosine and to facilitate the transfer of melanin.

In the process of melanogenesis intervene various hormones ensuring a regulation of the operation of which one can possibly foresee the addition and in particular the MSH (Melanocyte Stimulating
Hormone) which acts in conjunction with ultraviolet light and ACTH (Hormone Adreno Cortico Trophine Pituitary) to promote the passage of melanin in keratinocytes, which controls skin pigmentation. The preceding assembly thus makes it possible to induce and reinforce natural melanogenesis, the effects of which occur during the second phase of the tanning process.

 With regard to the first phase of the process, the invention uses compounds such as dihydroxyacetone, carrot oleoresin, St. John's wort extract or nut kernel extract, which have the advantage to stop type B ultraviolet (UVB).

 To better understand the technical characteristics and the advantages of the present invention, embodiments will be described, it being understood that these are not limiting as to their mode of implementation and the applications that can be used. make.

Example 1
The equivalent of 50 g of tyrosine and 25 g of phenylalanine are mixed in a vessel containing 50 ml of 5'-hydrochloric acid to ensure their hydrochlorination. The equivalent of 25 g of aspartic acid in the form of sodium aspartate is slowly added. . Stirred for 30 minutes at room temperature, then adjusted to pH 5 with a basic solution
Example 2
In 100 ml of sodium hydroxide solution at pH 12, 55 g of L tyrosine and 15 g of phenylalanine are added. Then 30 g of aspartic acid are gradually added. After stirring at a temperature of 350 ° C., for 30 minutes the citric acid is added in an amount sufficient to lower the pH to 6.5. A stable microcolloid is obtained.
Examples 3 to 14
The following compositions are prepared in which the nine overhead components according to the invention are integrated with the others under the conventional conditions with the aqueous phases and the oily phases prepared separately and then combined, always by any conventional means.
Tyrosine, phenylalanine and aspartic acid are integrated in the form of aqueous solution (composition according to Example 1) or microcolloidal (composition according to Example 2). Composition 3 is in the form of a milk that is particularly suitable as a tanning preservative; composition 4 as an adaptation cream; 5 as an intensifying cream and 6 as a tanning cream. The compositions 7, 8, 9 and 10 are creams that are particularly suitable for the induction of tanning. The compositions 11, 12, 13 and 14 are very good tanning activation creams.

<SEP>% <SEP> by weight <SEP> Comp <SEP> 3 <SEP> Comp <SEP> 4 <SEP> Comp <SEP> 5 <SEP> Comp <SEP> 6 <SEP> Comp <SEP> 7 <SEP > Comp <SEP> 8 <SEP> Comp <SEP> 9 <SEP> Comp10 <SEP> Comp11 <SEP> Comp12 <SEP> Comp13 <SEP> Comp14
<tb> L <SEP> tyrosine <SEP> 0.2 <SEP> 2 <SEP> 2 <SEP> 0.4 <SEP> 0.3 <SEP> 1 <SEP> 0.3 <SEP> 1 <SEP> 0.3 <SEP> 1 <SEP > 0.3 <SEP> 1
<tb> phenylalanine <SEP> 0.1 <SEP> 1 <SEP> 0.5 <SEP> 0.2 <SEP> 0.1 <SEP> 0.3 <SEP> 0.1 <SEP> 0.3 <SEP> 0.1 <SEP> 0.3 <SEP> 0.1 <SEP > 0.3
<tb> acid <SEP> aspartic <SEP> 0.1 <SEP> 1 <SEP> 1 <SEP> 0.2 <SEP> 0.15 <SEP> 0.5 <SEP> 0.15 <SEP> 0.5 <SEP> 0.15 <SEP> 0.5 <SEP > 0.15 <SEP> 0.5
<tb> escin <SEP> 0.05 <SEP> 0.5 <SEP> 0.3 <SEP> 0.1 <SEP> 0.05 <SEP> 0.1 <SEP> 0.05 <SEP> 0.1 <SEP> 0.05 <SEP> 0.1 <SEP> 0.05 <SEP > 0.1
<tb> Gluconate <SEP> of <SEP> Cu <SEP> 0.01 <SEP> 0.01 <SEP> 0.01 <SEP> 0.01 <SEP> 0.01 <SEP> 0.01 <SEP> 0.01 <SEP> 0.01 <SEP> 0.01 <SEP > 0.01 <SEP> 0.01 <SEP> 0.01
<tb> hydrolyzed collagen <SEP><SEP> 1.5 <SEP> 2.5 <SEP> 1.5 <SEP> 1.5 <SEP> - <SEP> - <SEP> - <SEP> - <SEP> - <SEP> - <SEP > - <SEP> oleoresin <SEP> of <SEP> carrot <SEP> 0.15 <SEP> 0.15 <SEP> 0.15 <SEP> 0.15 <SEP> 0.05 <SEP> 0.15 <SEP> 0.05 <SEP> 0.15 <SEP> 0.05 <SEP> 0.15 <SEP> 0.05 <SEP> 0.15
<tb> extract <SEP> husk <SEP> from <SEP> walnuts <SEP> and <SEP> St. John's Wort <SEP> 1 <SEP> 0.5 <SEP> 1 <SEP> 1 <SEP> 0.5 <SEP> 0.5 <SEP > 0.5 <SEP> 0.5 <SEP> 0.5 <SEP> 0.5 <SEP> 0.5 <SEP> 0.5
<tb> dihydroxy <SEP> acetone <SEP> 0.5 <SEP> 1.5 <SEP> 1 <SEP> 0.5 <SEP> - <SEP> - <SEP> - <SEP> - <SEP> - <SEP> - <SEP> - <SEP> acid <SEP> 18 <SEP> beta <SEP> glycyrrhetinic <SEP> 0.01
<tb> alcohol <SEP> Cetyl <SEP> 1 <SEP> 2 <SEP> 2 <SEP> 2
<tb> borax <SEP> 0.3 <SEP> 0.3 <SEP> 0.3
<tb> cholesterol <SEP> 0.1 <SEP> 0.1 <SEP> 0.1
<tb> wax <SEP> of bees <SEP> 2 <SEP> 2 <SEP> 2
<tb> dyes <SEP> 1.6 <SEP> 1.6
<tb> preservatives <SEP> 3 <SEP> 0.3 <SEP> 0.3 <SEP> 0.3
<tb> emulsifiers <SEP> and <SEP> agents <SEP> of <SEP> consistency <SEP> 4 <SEP> 10 <SEP> 10 <SEP> 10 <SEP> 10 <SEP> 10 <SEP> 9 <SEP > 9 <SEP> 9 <SEP> 9 <SEP> 9 <SEP> 9
<tb> extract <SEP> unsaponifiable <SEP> from <SEP> alfalfa <SEP> 0.1 <SEP> 0.1
<tb> solar <SEP> filters <SEP> 5 <SEP> 5 <SEP> 4 <SEP> 4 <SEP> 5 <SEP> 5 <SEP> 2.5 <SEP> 2.5 <SEP> 4 <SEP> 4
<tb> avocado oil <SEP><SEP> 1 <SEP> 1 <SEP> 0.5 <SEP> 0.5 <SEP> 0.5 <SEP> 0.5 <SEP> 0.5 <SEP> 0.5 <SEP> 0.5 <SEP> 0.5
<tb> oil <SEP> of <SEP> germ <SEP> of <SEP> wheat <SEP> 0.5 <SEP> 0.5 <SEP> 0.5 <SEP> 0.5 <SEP> 0.5 <SEP> 0.5 <SEP> 0.5 <SEP > 0.5 <SEP> 0.5 <SEP> 0.5 <SEP> 0.5
<tb> oil <SEP> of <SEP> petrolatum <SEP> 15 <SEP> 14 <SEP> 14 <SEP> 14 <SEP> 22 <SEP> 22 <SEP> 21 <SEP> 21 <SEP> 23.5 <SEP > 23.5 <SEP> 23 <SEP> 23
<tb> lanolin <SEP> 3 <SEP> 27 <SEP> 27 <SEP> 27 <SEP> 27 <SEP> 27 <SEP> 27 <SEP> 27 <SEP> 27
<tb> palmitate <SEP> of <SEP> cetyl
<tb> palmitate <SEP> of <SEP> vitamin <SEP> A <SEP> 0.1 <SEP> 0.1 <SEP> 0.1 <SEP> 0.1 <SEP> 0.1 <SEP> 0.1 <SEP> 0.1 <SEP> 0.1 <SEP > 0.1 <SEP> 0.1 <SEP> 0.1
<tb> perfume <SEP> 0.5 <SEP> 0.5 <SEP> 1 <SEP> 1 <SEP> 1 <SEP> 1
<tb> propylene <SEP> glycol <SEP> 1.2
<tb> Stearin <SEP> 3 <SEP> 2.5 <SEP> 2.5 <SEP> 2
<tb> triethanolamine <SEP> to <SEP> 85 <SEP>% <SEP> 1 <SEP> 0.2 <SEP> 0.2 <SEP> 1
<tb> Vitamin <SEP> F <SEP> 0.3 <SEP> 0.3 <SEP> 0.2 <SEP> 0.2 <SEP> 0.2 <SEP> 0.2 <SEP> 0.2 <SEP> 0.2 <SEP> 0.2 <SEP> 0.2
<tb> Vaseline <SEP> 35 <SEP> 35 <SEP> 35 <SEP> 35 <SEP> 35 <SEP> 35 <SEP> 35 <SEP> 35
<tb> water <SEP> demineralized <SEP> qs <SEP> qs <SEP> qs <SEP> qs <SEP> qs <SEP> qs <SEP> qs <SEP> qs <SEP> qs <SEP> qs <SEP > qs <SEP> qs
<Tb>
All of these compositions have been tested on animals and on humans under the conditions defined below. No adverse effects, and even more so, no toxic effects, have been found.

First series of experiments
Compositions 3 to 14 were tested on agouti mouse tails. The sections were examined after conventional staining with hematoxylin and saffron escin. Special stains were performed: melanocyte-specific Masson-melanine staining and S100 protein-specific immunoperoxidase research, which is also found in melanocyte cells. In these two series of trials, the assessment is quantitative as to the melanocyte richness of the epidermal layer.

In all cases we note the absence of dermal lesion and alteration of keratotic maturation. The conclusions were drawn after two weeks of testing, the first week corresponding to the initial phase mentioned above.

Composition 3 increase in melanocyte richness at the level of the basal layers with some melanocytes at the intermediate layers (Masson melanine and protein S 100 (++))
Composition 4 increase in the number of melanocytes in the basal layers with the presence of migrating melanocytes in the intermediate layers (Masson melanine and protein S 100 (+++))
Composition 5 increase in the number of melanocytes in the deep epidermal layers with the presence of some migrating melanocytes at the intermediate layers. No alteration of the keratotic maturation; absence of dermal lesion (Masson melanine and S100 protein (+++))
Composition 6: increase in the number of melanocyte cells at the level of the deep epidermal layers with the presence of melanocytes during migration in the intermediate layers; no alteration of keratotic maturation; absence of underlying dermal lesions (Masson melanine and protein S100 (++))
Compositions 7, 9 and 11 increase in the number of melanocytes at the level of the deep epidermal layers with the presence of melanocytes migrating at the level of the intermediate cells; absence of alterations in keratotic maturation; absence of dermal lesions (Masson melanine and pro tein sioe (+++))
Compositions 8, 10 and 12 increase of the proportion of melanocytes at the level of the deep epidermal layers with increase of the mitotic index. Presence of melanocytes in migration at the level of the cells. intermediate.

No impairment of keratotic maturation (Masson melanine and S100 protein (+++))
Compositions 13 and 14 presence of an increase in the proportion of melanocytes in the deep epidermal layers with increased mitotic index. Presence of melanocytes at the intermediate layers; absence of alterations in keratotic maturation (masson melanin and protein SIC (+++))
In all cases, there was no increase in the mitotic index.

Second series of tests
Compositions 3 to 14 were tested on human groups of 6 people: 3 men (1 from 20 to 35 years old, one from 36 to 50 years, one over 51 years old) and 3 women in the same age ranges . One arm was subjected to daily digital application of the composition and the other to daily digital application of a compositionequivalent but not containing the first nine components of the table above, that is to say the components within the scope of the present invention. These control applications therefore contained the same solar protective filters.

The tests were conducted for two weeks for each pair of composition (according to the invention and control composition), in summer, in usual sunshine in the French Mediterranean south.

The treated arms according to the invention all had a first phase of superficial coloration (as indicated above) extending over a week or so, the increase in the melanocyte richness corresponding to the second phase, appearing between 5 to 8 days. cleared the start of treatment, according to the subjects and their ability to tan checked on the control arm.

In all cases, melanogenesis was accelerated and enhanced on the test arm compared to the control arm, and the results intersected those of the animal tests.

No lesions or alterations in keratotic maturation were observed
The reactions of the various subjects (six by composition) made it possible to define more precisely the effectiveness of each composition and to choose the technical field of application mentioned above.

In addition, it has been found that, in the case of women of the two lower age ranges, with more sensitive skin than average, the particular quality of the results obtained with compositions 9, 10, 13 and 14 is found.

Other tests were carried out with different compositions which allow us to conclude that, approximately, compared to the
Tyrosine, the phenylalanine content can vary between 0 and 80% with the best results between 20 and 60%, that of aspartic acid between 30 and 70% with the best results between 45 and 65% *
The total weight content in this set L tyrosinase, phenylalanine and aspartic acid, relative to the final compositions, is preferably approximately between 0.1 and 10% and the best results are obtained between 0.25 and 6%.

The contents by weight relative to the final composition are preferably approximately as follows: 0.01 to 1% Cu gluconate 0.001 to 0.10% Core oleoresin 0.01 to 0.40% Walnut extract and St. John's wort 0.1 to 2% hydrolyzed collagen from 0 to 5% di-hydroxy acetone from 0 to 3%
It should be noted that carrot oleoresin can be substituted for 0.5 to 4% of carotene 3 relative to carrot oleoresin, which gives from 0.005 to 0.16% of carotene ss relative to the total composition, but preferably limited to 0.10%.

It is also noted that walnut and St. John's wort extract containing naphthoquinone tructure compounds (juglon and tannins, hypericine and flavone compounds) it is possible to replace this extract with one or more of these active substances.

Comparative tests were carried out with compositions of the prior art which demonstrated the superior effectiveness of the compositions according to the invention, the non-increase of the mitotic index. In fact, the first phase of the process according to the invention provides the skin with a reconstituted pigment having an effect equivalent to that of melanin while during the second phase, the transfer of constituents inducing, assisting or reinforcing melanogenesis takes place. natural.

It will also be noted that the presence of Cu ++ ions and other components such as collagen reinforce and protect these actions while certain compounds of the prior art are avoided. For example it is common to use sulfur compounds such as glutathione which has a well-known inhibitory effect in the chain of melanogenesis reactions.

It will also be mentioned that the pH of the water-soluble compositions such as those of Examples 1 and 2 is preferably between 4.5 and 6.9.

Claims (18)

 A method for the hydrosolubilization of tyrosine, phenylalanine and aspartic acid characterized in that sodium in the salt base state is added and the pH adjusted to a value in the range of 4.5 to 6 9  2. Method according to claim 1 characterized in that tyrosine and phenylalanine are added hydrochloric acid which ensures their hydrochlorination then sodium aspartate, the pH is then adjusted to give an acid solution  3. Method according to claim 1 characterized in that tyrosine and phenylalanine are added to sodium hydroxide solution, aspartic acid is then added with stirring; the pH being anus to give a stable and acidic microcolloid  4. Composition for skin tanning comprising tyrosine and aspartic acid characterized in that it contains phenylalanine forming with tyrosinase and aspartic acid a water-soluble combination; this combination being itself supplemented by at least one reconstituted pigment ensuring the coloration during a first phase, before transfer of the constituents of the association  5. Composition according to Claim 4, characterized in that the water-soluble combination is obtained by the process according to one of Claims 1 to 3.  6. Composition according to one of claims 4 to 5 characterized in that it contains escin  7.Composition according to one of claims 4 to 6 characterized in that it contains Cu ++ ions  8. Composition according to one of claims 4 to 7 characterized in that it contains collagen  9. Composition according to one of claims 4 to 8 characterized in that it contains dihydroxy acetone  10. Composition according to one of claims 4 to 9 characterized in that it contains oleoresin carrot  11. Composition according to one of claims 4 to 10 characterized in that it contains walnut extract extract  12.Composition according to one of claims 4 to 11 characterized by the fact that it contains St. John's wort extract  13. Composition according to one of claims 4 to 12 characterized in that the weight content of phenylalanone relative to tyrosine is between 0 and 80%  14. Composition according to one of claims 4 to 13 characterized in that the weight content of aspartic acid relative to tyrosinase is between 45 and 65%  15. Composition according to one of claims 4 to 14, characterized in that the tyrosinase is L tyrosine  16. Composition according to one of claims 4 to 15 characterized in that the combination tyrosine, phenulalanine, aspartic acid is 0.25 to 6% by weight of the final composition  17. Skin tanning process characterized in that it comprises a first reconstituted pigment supply phase and a second component transfer phase inducing, assisting or reinforcing the natural melanogenesis.  18. The method of claim 17 characterized in that it uses a composition according to one of claims 4 to 16.