CH682453A5 - Use of compounds based on nucleic acids and / or derivatives thereof for preparing pharmaceutical or cosmetic compositions. - Google Patents

Abstract

The invention relates to a cyto-photo-protector agent for protecting the skin, specially the Langerhans cells. Said agent is characterized in that it is comprised of at least one compound selected amongst the group of nucleic compounds and derivatives including: A - ribonucleic acids, as well as their derivatives, preferably their salts, with mineral or organic bases, preferably complex salts of basic proteides, basic aminoacids or basic peptides; and B - ribonucleotides as well as their derivatives of the salt type, with mineral or organic bases including complex salts with basic proteides, basic aminoacids or basic peptides; and C - ribonucleosides. It is thus possible to prepare cosmetic and/or dermopharmaceutical compositions for topical utilization and which have a photoprotecting activity on teguments, but more particularly on living cells of the derm and the epiderm, thus providing for a cytoprotection of the skin, particularly epiderm immunocompetent cells; Langerhans cells sensitive to solar radiation and also by contact with certain compounds frequently used as conventional solar filters.

Description

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Description

The invention relates to the use of compounds based on nucleic complexes: ribonucleoproteins, ribonucleotides, ribonucleosides, for the preparation of cosmetic or der-pharmaceutical compositions. These compounds are intended for topical use. The invention also relates to such compositions and to new compounds constituted, for example, by associations with preferably biological photo-protectors, particularly those existing in the epidermis having a direct photo-protective action such as keratin, urocanates, certain amino acids, either an indirect action such as tyrosine compositions, tryptophan stimulators of melanin biosynthesis (which is recognized as one of the best natural photo-protective agents against the harmful effects of solar or UV radiation).

Numerous photo-protective agents for the skin are already known in the prior art. For example, document FR-A 2 026 267 describes the use of combination with uracil, cytosine, gua-nine and / or 5-chloro-uracil as photo-protective agents for the skin. , photo-protection control tests being given by determining the "average protection factor" according to SCHULZE (Parfumerie und Kosmetik 2L 310/365 (1956)). In the latter document, combinations of these substances are also described, which are purine, pyrimidine bases with conventional photoprotective agents such as cinnamates, in particular ethylhexyl pmethoxycinnamate.

However, these purine or pyrimidine bases are little or not soluble in water.

Also known from the prior document of the applicant EP-B 10 483 are accelerating tanning agents, thus resulting in photo-protection of 1 skin, based on arginine tyrosinate and providing combinations with urocanic acid or urocanates. arginine. Tanning accelerators have a photo-protective effect by stimulating the formation of melanin. Also described in FR-A 2,579,461 are amides of urocanic acid as a sunscreen.

Document FR-A 2,511,243 also discloses the use of highly polymerized DNA mainly in cosmetic compositions such as creams, milks or lotions, to improve elasticity or cell regeneration. It is mentioned in this document a possibility of protecting the skin from the harmful rays of the sun. However, in the context of sun milk, it is proposed to add an ultraviolet resistant sun filter which it is indicated that it must be non-sensitizing.

None of them has been described by the author.

Furthermore, various nucleic acid derivatives have been described as such, in certain cases with a therapeutic application mainly for combating asthenia of hepatic insufficiency (see FR-A 2 329 289; FR-A 2 181 220; US -A 3 326 892; AU-B 461 034; FR-A 1 440 795; FR-A 2 354 774; FR-A 2 113 774; BSM-A 3 932; BSM-A 5 032 and BSM-A 4 811 ).

All known photo-protective agents are intended to protect the skin against the dangers of excessive or chronic sun exposure, the harmful effects of which are well known to be mainly linked to ultraviolet radiation, such as UVB and UVA. We know that these harmful effects are manifested by acute manifestations ranging from simple solar perythema to skin necrosis, passing through burns of different degrees; late effects resulting from prolonged and repeated exposures leading to early skin aging; finally long-term skin carcinogenic effects, following chronic UVR exposures.

Photo-protection has therefore long appeared as a necessity to guard against the harmful effects of solar radiation.

Thus, many so-called solar cosmetic products have been marketed which must provide a guarantee against the harmful effects of the sun, applied topically and containing various varieties of photo-protective agents or sunscreen agents, of which representative examples are given by the documents mentioned above.

For consumers, the photo-protective efficacy of these “solar” products is specified on the products by the indication of photo-protection index or S.P.F. (Sun Protecting Factor) determined by photobiologists on series of voluntary subjects of current phototypes, according to official methods.

These methods are based in particular on the visual determination of the MED (Minimum Erythemal Dosis) corresponding to the smallest dose of UVR irradiation capable of producing, using a solar simulator, a visible erythema, with sharp edges, 24 h after irradiation.

But it appeared by histological checks that, well before the onset of the appearance of preliminary erythemes, cell damage was already occurring at UVR doses much lower than the MED. The SPF value is therefore not suitable for cytophoto-protection. Thus, it has been possible to observe the appearance in the epidermis of completely characteristic “sunburn cells” corresponding to epidermal keratinocytes damaged by UVR at doses lower than the MED, therefore without the appearance of erythema has been noted. Thus, if cellular damage in the skin can appear at UVR doses lower than those producing a visible erythema, there is a manifest interest in not being satisfied with providing photo-protection making it possible to avoid solar erythema, but also to ensure real photo-protection of the living cells of the epidermis and dermis, which do not or badly bring sun filters aligned on a simple MED of average value, moreover generally unknown to users and more scalable.

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Among these living cells which may suffer damage by UVR, there may be mentioned mainly:

* For the epidermis:

- epidermal keratinocytes, essential for the protection of the skin, and in particular,

- Langerhans cells, a fundamental element of the cutaneous immune defense system. They play a fundamental role in the capture and processing of antigens:

. exogenous antigens: for example viruses, toxic substances, sensitizing substances,

. endogenous antigens: abnormal or transformed or even malignant epidermal cells.

According to B. GILCHREST (Barbara A. GILCHREST - SKIN * AGING PROCESSES - CRC Press - 1984

- pages 73, 87, 102, 103), if the number of Langerhans cells and their functionality (explored by the DNCB test) decreases with age in covered areas (physiological aging), this reduction is even more significant with l age in exposed areas compared to covered areas (actinic aging).

This alteration with age in the number and function of Langerhans cells, mainly linked to repeated sun exposure, leads to a decrease in the cutaneous immune defense system and in particular promotes skin and photo-carcinogenesis.

- other epidermal cells concerned: MERCKEL cells and melanocytes, the number and vitality of which decrease with age, which decreases the skin's self-photo-protection capacity by melanin pigments.

* For the dermis:

- fibroblasts-fibrocytes, responsible for the biosynthesis of the constituent elements of the dermis.

Furthermore, the present inventors wished to verify whether the sun preparations and possibly the conventional sun filters, such as cinnamates and PABA esters, would not be capable of having a cytotoxic or photo-cytotoxic effect on living cells. of the epidermis and / or dermis of which they must provide photo-protection, and in particular on the Langerhans cells which constitute the essential element of the cutaneous immune capital.

However, the present inventors were able to unexpectedly discover that the filters tested, brought into contact with live epidermal and dermal cells, under in vivo and in vitro conditions were not only poorly tolerated, but exhibited a non-negligible cytotoxicity, particularly in in-control vitro. With regard to Langerhans cells, the filters commonly used behave like haptens and, therefore, block or alter the essential immunological response function of Langerhans cells. This process manifests itself inter alia by blocking the HLADR site which plays a crucial role in the recognition and presentation of antigens.

However, cyto-photo-protection becomes aberrant if the photo-protective agent is itself cytotoxic or disrupts function.

The finding of cytotoxicity of known sunscreens tested on contact with the abovementioned living cells suggests that the risk exists not only in cell culture, but in vivo in the event that these filters could cross the skin by simple topical use.

However, recent work, carried out on various cinnamic esters, which are common photo-protective agents, demonstrate that, when they are introduced into solar cosmetic excipients, these filters penetrated relatively quickly into the skin, but in addition were present in circulating blood (see the pharmacy thesis of Mr CLAUS Denis presented at the University of Strasbourg FRANCE (1982), entitled "Study of photochemical stability and skin penetration of para-methoxycinnamic acid esters" ).

Similarly, other publications report sensitization and allergic reactions (among others the book of J. Foussereau having for title "Allergic eczemas, in the chapter: Anti-suns" published by MASSON editions in 1987, in particular pages 312-319, and the article by MAYBACH published in Contact Dermatitis 1978, pages 1665-1666, entitled "Allergy Contact Photo-dermatitis to PABA; the article by JEANMOUGIN published in Photo-dermatoses, page 180 concerning allergies and photo -Allergies of Contact; the article by DAVIES published in Contact dermatitis 1982, g, pages 190-192 entitled "Acute Photo-sentivity from sunscreen 2, EE PMC; the article by Horio published in Dermatologica 1978, 156. pages 124-128, entitled “Photo Contact Dermatitis from PABA”, the article by THOMSON and MAIBACH published in Arch Dermatology, 1977, 113. pages 1252-1253, also.

The present invention therefore has the pure aim of solving the new technical problem consisting in the supply of new specific cyto-photo-protective agents which can be used topically for long periods, cyto-compatible, and well tolerated in current topical use, even prolonged, as for products called “anti-aging” for daily use, preferably without the use of conventional sun filters.

The present invention also aims to solve the new technical problem consisting in the supply of new photo-protective agents having a specific activity of cellular photo-protection called cyto-photo-protection, in particular for essential cells of the epidermis and dermis, such as keratinocytes, fibroblasts, and especially Langerhans cells.

The present invention also aims to solve the new technical problem consisting in the supply of new cytoprotective agents not behaving or essentially not behaving like haptens, therefore not blocking the essential immunological response function of Langerhans cells.

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The present invention also aims to solve these new technical problems stated above by providing such new skin photo-protective agents, which are also compatible and stable in most cosmetic or dermatological preparations, while being of preferably water-soluble, thus allowing better penetration into the epidermal layers, which makes it possible to differentiate the bio-cyto-photo-protective agents from conventional sun filters.

These new technical problems are solved for the first time by the present invention, in a simultaneous manner, usable on an industrial scale.

The objects of the present invention correspond to the definitions given in the appended set of claims.

Thus, the present invention provides, according to a first aspect, a cutaneous photo-protective agent, of biological or biotechnological origin, in particular having a photo-protective activity of functional skin cells, in particular Langerhans cells, of preferably not containing a synthetic cytotoxic sunscreen, in particular of the cinnamate or PABA type or their derivatives, characterized in that it comprises at least one compound chosen from the group of nucleic compounds and derivatives comprising:

A - Ribonucleic acids, as well as their derivatives, in particular their salts, with mineral or organic bases, and preferably complex salts of basic proteins, basic amino acids or basic peptides;

B - Ribonucleotides, as well as their salt type derivatives, with mineral or preferably organic bases including complex salts with basic proteins, basic amino acids or basic peptides; and

C - Ribonucleosides.

According to a particular embodiment, the ribonucleic acids are in the form of salts with mineral bases, advantageously chosen from NaOH, KOH, NH4OH, or organic bases, in particular ethanolamines.

According to another particular embodiment, the ribonucleic acids are in the form of their salts with basic proteins, such as:

- Histones or microproteins of molecular weight between 11,000 and 24,000 approximately, highly basic due to their richness in basic amino acids like Arginine and Lysine, which constitute up to 25% of the amino residues of these molecules. Preferred histones are those of the H1, H2A, H3, H4 type which are, for example, reported on page 818 of the book by A. LEHNINGER. Such histones are found in particular in the sperm of certain fish, leukocytes, the thymus and more generally in all cell nuclei;

- globins whose molecular weights are between approximately 15,000 and approximately 70,000, and which are rich in basic amino acids constituting the Histidine type (5 to 9%) and lysine.

According to another particular embodiment, the ribonucleic acids are in the form of their complex salts with basic amino acids, preferably chosen from L-histidine, L-argi-nine, L-lysine, ia L-hydroxylysine, L-ornithine.

According to another variant, the ribonucleic acids are in the form of their salts with basic peptides.

In addition, it should be observed that the complex salts of the abovementioned ribonucleic acids have the advantage of being water-soluble, of having good diffusibility in the epidermis and that they can be used at concentrations which make it possible to preferably obtain Bio-compatible pH between 5.8 and 8, the interstitial liquid medium being at a pH close to 7.4.

According to another particular embodiment of the invention, the aforementioned ribonucleotides are chosen from the group of natural mono-ribonucleotides, that is to say the normal constituents of the corresponding nucleic acids which have a strong UV absorbing power in the lengths d from 250 to 280 nm.

The preferred ribonucleotides are:

Preferably, the abovementioned ribonucleotides are used in the form of their salts with bases, which makes it possible to obtain pH values of the order of 5.8 to 8 which are biocompatible.

According to a particular embodiment, the abovementioned ribonucleotides are in the form of their salts with mineral bases, preferably chosen from NaOH, KOH, NH4OH, or with bases or-

AMP ADP

GMP GDP

CMP CDP

UMP UDP

IMP IDP

XMP XDP

ATP

GTP

CTP

UTP

ITP

XTP

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ganiques, in particular ethanolamines. An example of a particularly preferred salt is the sodium salt of ATP for its photo-cyto-protective effect specific to Langerhans cells.

According to another particular embodiment, the abovementioned ribonucleotides are in the form of their salts with basic proteins, such as:

- Histones or microproteins of molecular weight between 11,000 and 24,000 approximately. In particular, these are histones type H1, H2A, H3B, H3, H4 defined above.

- the globins or proteins formed by coupling hemoglobins and myoglobins whose molecular weights are between approximately 15,000 and approximately 70,000.

According to another particular embodiment of the invention, the abovementioned ribonucleotides are in the form of their salts with basic amino acids, in particular one or more basic amino acids chosen from the group consisting of L-histidine, L-arginine, L-ornithine, L-hydroxyly-sine, L-lysine.

According to another variant, the ribonucleotides are in the form of their salts with basic peptides.

According to another particular embodiment, the abovementioned ribonucleosides are chosen from the group consisting of natural monoribonucleosides, which are the normal constituents of the corresponding nucleic acids which have a strong UV absorbing power in the wavelengths of 250 to 280 nm, preferably :

RIBONUCLEOSIDES. Adenosine. Cytidine. Guanosine. Inosine. Uridine. Xanthosine

The advantage of ribonucleosides is that most of the time they directly present pHs compatible with cutaneous cellular physiology, therefore not a priori requiring the formation of salts, complexes or biochemical combinations with basic proteins, basic peptides and basic amino acids.

These nucleosides can, according to certain particular embodiments, be associated or combined with one or more of the abovementioned nucleoprotides or ribonucleotides as well as their salts, in proportions calculated for obtaining biocompatible pH between 5.8 and 8.

It will be understood that, according to the invention, it is preferred to use water-soluble cyto-photo-protective agents having good diffusibility in the epidermis, at concentrations allowing to obtain biocompatible pH or between 5.8 and 8.

It should be noted that the nature of the RNA nucleic acid or of the poly-ribonucleotides used for the formation of the derivatives according to the invention can be arbitrary. Indeed, it can be poly-ribo-nu-cleotides starting whose secondary or tertiary structure is conserved, but also ribonucleic acids resulting from the more or less partial denaturation of poly-ribo-nucleotides, because this denaturation more or less partial is not annoying. It is thus possible to use acids whose primary structure can be kept to the maximum, or the product of the denaturation-degradation, more or less managed of these primary structures, resulting in fragments of primary structure, ranging from poly- to oligo- and to mono-nucleotides and / or to the corresponding poly-, oligo- or mono-ribonucleosides.

This more or less partial denaturation is not a problem for the formation of the derivatives according to the invention used as cyto-photo-protective agents, because this use is above all not intended to translate the original genetic message of the RNA used for the preparation of the derivatives according to the invention.

It follows from the above that the purpose of the topical use of the derivatives according to the invention is to exert cyto-photo-protective effects by depositing the compounds according to the invention on or in the skin surface layers.

They thus play the role of chromophores or more advanced passive targets which will absorb or trap the energy of the radiation, competitively and preferentially, preventing the radiations from reaching the potential targets which it is really necessary to protect from radiation damage, constituted by active cell organelles and constituent macro-molecules.

In addition, the presence of the compounds according to the invention in large quantities, comprising poly-, oligo- and mono-ribonucleotides, salts, complexes, combinations and derivatives of poly-, oligo- and mono-ribonucleosides, is perfectly tolerated by cells since we naturally find a high percentage between 5 and 15% compared to the dry weight of living cells, and that we normally find in horny epidermal layers.

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The compounds according to the invention are therefore biological substances which are homologous or analogous to the substances naturally present in the epidermis.

It is preferred to use derivatives of ribonucleic acid or RNA constituents over DNA derivatives due to the fact that:

- RNA and derivative constituents are naturally present in eukaryotic cells at concentrations usually 2 to 8 times higher than DNA derivatives and thus come closer to the physiological cellular and tissue environment,

- RNA and ribonucleoderivatives appear to be less sensitive to UVB irradiation,

- RNAs are more labile to depoiymerisation and partial hydrolysis into nucleotides of their molecule than DNA, which is favorable for cyto-photo-protection of the skin,

- RNA are as essential to the normal functioning of skin cells as are DNA and proteins from these same cells.

According to another particular embodiment of the invention, the skin photo-protective agents according to the invention are characterized in that they also comprise derivatives of urocanic acid or urocanoprotides, since these derivatives have a synergistic effect with the preceding compounds ribonucleoprotides, ribonucleotides and ribonucleosides.

These derivatives of urocanic acid or urocanoprotides are simple or complex salts of urocanic acid or derivatives of urocanic acid with certain proteins, peptides, amino acids.

These derivatives of urocanic acid or urocanoprotides in the form of complex salts are preferably obtained by a combination of urocanic acid with:

a) basic proteins, advantageously histones or globins, in particular, as previously defined;

b) ribonucleotides such as AMP, ADP, ATP;

c) basic peptides,

d) basic amino acids, preferably L-histidine, L-arginine, L-lysine, L-hydroxylysine, L-orni-thine, taken alone or in combinations.

It will be understood that the aim of these biochemical combinations is to produce hydrosolubic biological complex salts unlike urocanic acid which is little or insufficiently and more cyto-compatible than the urocanates of Na, K.

These urocanic derivatives develop a very strongly UVR absorbing effect, in particular in the bands 265, 290 to 320 nm, these compounds being all the more UV absorbent as they are associated with ribonucleotides, proteins, peptides, amino acids themselves. same photo-absorbents in the absorption band extending from 265 to 320 nm.

They are interesting, because they are soluble, clearly substantive and their solutions can be adjusted to physiological pH from 6.0 to 8.0, depending on the proportions of each of the constituents.

Another particularly advantageous, unexpected effect of the cyto-photo-protective agents of the invention lies in the fact that the combination of the derivatives of urocanic acid with the cyto-photo-protective agents of the invention carried out a natural process skin photo-defense. It can be observed that the proportion of urocanic salts and complexes increases considerably, up to 10 times, in the epidermis and particularly in the reservoir part of the stratum corneum after the solar irradiations and following the thermal stimuli of the sweat glands by the solar infrared radiation.

According to the invention, preference is given in the urocanic derivatives to the urocanoprotidic complexes, namely the urocanohistones, urocano-peptides, basic urocano-amino acids and urocano-nu-cleotides more cytophilic than the alkaline or alkaline mineral derivatives or salts. earthy.

According to another particular embodiment of the invention, the cytoprotective agents for the skin according to the invention also comprise amino acids and peptides or proteins.

Advantageously, these amino acids and these peptides and proteins are chosen from:

1) one or more of the 20 amino acids which occur naturally in proteins, the list of which follows:

. Amino acids involved in the complexes, aforementioned combinations L-histidine, L-arginine, L-lysine, L-citrulline, L-ornithine, L-hydroxylysine.

. Aromatic amino acids L-tyrosine, L-phenylalanine, L-tryptophan. Very advantageous, since they themselves have a significant absorbing UVR effect in the 280 nm band.

. Dicarboxylic amino acids: L-glutamic acid, L-aspartic acid.

. Cyclic amino acids: L-proline * (L-hydroxyproline).

. Monocarboxylic amino acids: glycine, alanine, L-valine *, L-leucine *, L-isoleucine.

. Amino acids "alcohol": L-serine *, L-threonine *.

. "Amidated" amino acids: L-glutamine *, L-asparagine.

. Sulfur amino acids and sulfur oligo-peptides: L-cysteine *, L-methionine *, cystine *,

'' Epidermal amino acids abundant in keratin, the photoprotective power of which is known.

2) One or more of the usual peptides and proteins of cells and / or peptides resulting from acid, basic or enzymatic hydrolysis, of polypeptides and / or scleroprotein proteins and soluble proteins.

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For example: GLUTATHION: perfectly water-soluble tripeptide and usually present in all living tissues at high concentration (5 mM) and which plays an important role in the intracellular transport of amino acids and in biological redox reactions.

Hormonal peptides are excluded from the present invention. By cons are advantageously complementary, the. Scleroproteins and their partial hydrolysates.

For example:

- silk fibroin concentrations from 1 to 10%

- collagen concentrations from 1 to 10%

- elastin concentrations from 1 to 10%

- hydrophilic keratins

. Soluble proteins and their partial hydrolysates:

For example: (in concentrations of 0.10 to 10%)

- histones

- globins (hemoglobins and myoglobins)

- plasma proteins (eg serum albumin, serum globulin)

- partially hydrolyzed plasma proteins (enzymatic pathway), ie blood plasma rich in proteins (about 8%) and usable as synergistic biological solvent for photo-protection and biological transporter vehicle, thanks to the osmotic pressure that it develops, particularly active and at its original pH 7.4 to dissolve and diffuse the aforementioned ribonucleo-derivatives.

The advantage of these peptides and proteins is that they themselves have a photo-absorbing power in the ultraviolet spectrum:

- in the 250 to 300 nm zone (absorption resulting mainly from the presence of the 3 aromatic amino acids: tyrosine-tryptophanephenylalanine,

- in the 210 to 250 nm zone (absorption due in particular to amino acids: cysteine, methionine, histidine),

- in the zone less than 210 nm (absorption due to peptide bonds),

and that they can be used in synergy with all the aforementioned nucleoprotides and all the aforementioned urocanoprotides reinforcing the cyto-photo-protective power of the preceding ones.

The present invention covers, according to a second aspect, the cosmetic or dermo-pharmaceutical compositions with cyto-photo-protective activity of the skin, in particular with cellular photoprotective activity and early cutaneous anti-aging, in particular protective of Langerhans cells, characterized in that 'They include at least one cyto-photo-protective agent as defined above.

In these cosmetic or dermo-pharmaceutical compositions according to the invention, the total concentration of photo-protecting agents according to the invention is usually similar to the concentrations of previously known photo-protecting agents used for photo-protecting the skin. This concentration of active principle (s) according to the invention will advantageously be between 0.01% and 10% by weight, preferably 0.1 to 3%, relative to the total weight of the cosmetic or dermal composition. pharmaceutical.

Any type of usual excipient of such cosmetic or dermo-pharmaceutical compositions can be used for topical use.

The present invention also relates, according to a third aspect, to new compounds, characterized in that they are the compounds chosen from the group consisting of:

A - The simple or complex salts of the ribonucleic acids previously stated with organic bases, chosen from the consisting groups of basic proteins such as histone, globin, basic peptides, or peptides such as glutathione.

B - The simple or complex salts of the ribonucleotides previously described, with the organic bases chosen from the groups consisting of basic proteins and basic peptides mentioned above.

According to a variant, the ribonucleotides are chosen from:

Finally, according to a fourth aspect, the present invention also relates to a process for the preparation of a cyto-photo-protective agent for the skin, in particular Langerhans cells, characterized in that one uses, as cyto agent -photo-protector, at least one compound chosen from the group consisting of

AMP ADP

GMP GDP

CMP CDP

UMP UDP

IMP IDP

XMP XDP

ATP

GTP

CTP

UTP

ITP

XTP

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sisting of the compounds and derivatives nuciéoprotidiques and ribonucleoside previously defined. The particular embodiments for the preparation of these cyto-photo-protective agents for the skin also resulting from the preceding description.

According to a particular embodiment of the preparation process according to the invention, the salts of the ribonucleic acids are prepared with mineral or organic bases, or better still the complex salts with basic proteins, amino acids or basic peptides as defined above, according to a classic complete acid or base reaction, or partial, in the case of complex salts.

According to another embodiment of the method according to the invention, the salts of the ribonucleotides are prepared with mineral or organic bases including complex salts with basic proteins, basic amino acids or basic peptides, as defined above, also according to a classic acid-base reaction.

The present invention also relates to a process for the preparation of cosmetic and / or dermo-pharmaceutical compositions, characterized in that at least one cyto-photo-protective agent of the skin is incorporated as previously defined in a cosmetologically excipient, vehicle or support and / or pharmaceutically compatible.

Other objects, characteristics and advantages of the invention will appear clearly in the light of the explanatory description which will follow, given with reference to multiple examples of the invention, given simply by way of illustration and which in no way can be how to limit the scope of the invention. In the present description, in particular the examples, all the percentages are given by weight, unless otherwise indicated.

EXAMPLE 1

Preparation of a mineral base ribonucleate.

For example, a potassium ribonucleate is prepared in the following manner:

5.7 ml of 0.5 N KOH are used to dissolve 1 g of RNA previously dispersed in 2 g of distilled water.

A solution is thus obtained at pH: 6.85.

This addition of ribonucleic acid is carried out with vigorous stirring for a few minutes. The potassium ribonucleate thus prepared is separated in the following manner:

to obtain the potassium ribonucleate in the form of a pale yellow-white powder, it is sufficient to lyophilize this solution quickly. The following physicochemical characteristics are obtained:

- ultraviolet spectrum (distilled water) = maximum 260 nm,

- pH (aqueous solution) prepared as above = 6.85.

The sodium or ammonium ribonucleates are prepared in the same way from the corresponding mineral bases NaOH, NH4OH.

EXAMPLE 2

Protein ribonucleate

The histone ribonucleate is prepared using, for example, RNA (commercial quality.

An aqueous solution of histone (type IV very rich in Arginine) is prepared.

To this aqueous solution, the RNA is added with stirring in small quantities,

stir until completely dissolved and a pH of 6.8 is obtained.

The separation of the histone ribonucleate obtained is done: by lyophilization, or by thanol at 96 °. Centrifugation - washing with anhydrous ethanol - drying under vacuum.

Ultraviolet spectrum wavelength: 258-262 nm.

EXAMPLE 3

Basic amino acid ribonucleate

Arginine, histidine and lysine 3 - A ribonucleates are prepared - A - Arainine ribonucleate

- In an Erlenmeyer flask, 0.665 g of L-arginine are dissolved by stirring in 100 ml of distilled water.

- 1.335 g of CODEX RNA is added gradually, in small fractions, with stirring, at laboratory temperature.

- Continue stirring until complete dissolution (approximately 1 hour).

- The liquid obtained is filtered and dehydrated for example by lyophilization: obtaining a white powder.

CODEX) available, then precipitation continues with the

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(yield: about 95%).

. Ultraviolet spectrum (distilled water): maximum 258 nm. pH (distilled water): 6.3.

3 - B - Histidine ribonucleate

- In an Erlenmeyer flask, 0.947 g of L-histidine is dissolved by stirring in 100 ml of distilled water.

- 1.053 g of CODEX RNA is added gradually, in small fractions, with stirring, at laboratory temperature.

- Continue stirring until complete dissolution (around 12 hrs).

- The liquid obtained is filtered and dehydrated for example by lyophilization: obtaining a white powder.

(Yield: about 95%).

. Ultraviolet spectrum (distilled water): maximum 258 nm. pH (distilled water): 6.4

3 - C - Ivonin's ribonucleate

- In an Erlenmeyer flask, 0.619 g of L-lysine are dissolved by stirring in 100 ml of distilled water.

- 1.481 g of CODEX RNA is added gradually, in small fractions, with stirring, at laboratory temperature.

- Continue stirring until complete dissolution (approximately 1 hour).

- The liquid obtained is filtered and dehydrated, for example by lyophilization: obtaining a white powder.

(Yield: about 95%).

. Ultraviolet spectrum (distilled water): maximum 258 nm. pH (distilled water): 6.2

EXAMPLE 4

Mineral base ribonucleotidate

By proceeding generally as described in Example 1, the following mineral base ribonucleotides are prepared:

4-A. Sodium cytidine monophosphate

4-B. Uridine sodium monophosphate

4-C. Inosine sodium monophosphate

4-D. Sodium adenosine diphosphate

4-E. Adenosine sodium triphosphate

4-F. Guanosine sodium monophosphate

4-G. Sodium adenosine monophosphate

EXAMPLE 5

Protein ribonucleotidate

The following protein ribonucleotidates are prepared according to the following procedure:

- Histone monophosphate cytidine.

The preparation takes place as follows, the cytidine monophosphate being very soluble in water, as well as the histone, it suffices to prepare respective solutions of 1% and to mix them until a pH of between 6 and 7, then lyophilize the preparation obtained.

Average UV absorption = 270 nm.

EXAMPLE 6

Peptide ribonucleotidate

The following peptide ribonucleotidates are prepared:

- Protidine cytidine monophosphate according to the same process as in Example 5.

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EXAMPLE 7

Amino acid ribonucleotidate

The following basic amino acid ribonucleotides are prepared:

7 - A - Cvtidine arainine monophosphate

- In an Erlenmeyer flask, 0.857 g of L-arginine is dissolved by stirring in 100 ml of distilled water.

- 1.143 g of cytidine monophosphate is added gradually, in small fractions, with stirring, at laboratory temperature.

- Continue stirring until complete dissolution.

- The solute obtained is filtered and dehydrated, for example by lyophilization.

- Obtaining a beige powder (Yield: about 95%)

. Ultraviolet spectrum (distilled water): maximum 272 nm

. pH (distilled water): 6.2.

7 - B - Cvtidine histidine monophosphate

- In an Erlenmeyer flask, 1.07 g of L-histidine is dissolved by stirring in 100 ml of distilled water.

- 0.93 g of cytidine monophosphate is added gradually in small fractions, with stirring, at laboratory temperature.

- Continue stirring until complete dissolution.

- The solute obtained is filtered and dehydrated, for example by lyophilization.

- Obtaining a beige powder (Yield: about 95%).

. Ultraviolet spectrum (distilled water): maximum 272 nm

. pH (distilled water): 6.2.

7 - C - Adenosine arginine triphosphate

- In an Erlenmeyer flask, 0.966 g of L-arginine is dissolved by stirring in 100 ml of distilled water.

- 2.034 g of sodium adenosine triphosphate are added gradually in small fractions, with stirring, at laboratory temperature.

- Continue stirring until complete dissolution.

- The solute obtained is filtered and dehydrated, for example by lyophilization.

- Obtaining a beige powder (Yield: about 95%).

. Ultraviolet spectrum (distilled water): maximum 260 nm

. pH (distilled water): 6.7.

7 - D - Histidine adenosine triphosphate

- In an Erlenmeyer flask, 1 g of L-histidine is dissolved by stirring in 100 ml of distilled water.

- 1 g of sodium adenosine triphosphate is added gradually, in small fractions, with stirring, at laboratory temperature.

- Continue stirring until complete dissolution (approximately 1 hour).

- The solute obtained is filtered and dehydrated, for example by lyophilization.

- Obtaining a beige powder (Yield: about 95%).

. Ultraviolet spectrum (distilled water): maximum 259 nm

. pH (distilled water): 6.6.

EXAMPLE 8 Ribonucleosides

The following ribonucleosides are commercially available:

8-A

. Adenosine

8-P

. Cytidine

8-C

. Inosine

8-D

. Uridine

8-E

. Uridine / cytidine (50/50)

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EXAMPLE 9 Uride protein

The histone urocanate is prepared by operating in a similar manner to the preparation of the Protamine urocanate set out in Example 10, but operating at a temperature <50 ° C.

EXAMPLE 10

Peptide urocanate

Protamine urocanate is prepared in the following manner:

- In an Erlenmeyer flask, 1.40 g of protamine is dissolved by stirring in 100 ml of distilled water.

- 1.40 g of urocanic acid is added gradually.

- Continue stirring at 70 ° C, until complete dissolution.

- Filter and dehydrate, for example by lyophilization.

- Obtaining a beige powder (Yield: around 90%).

. Ultraviolet spectrum (distilled water): maximum 269 nm.

EXAMPLE 11

Basic amino acid urocanate

The arginine and histidine urocanates are prepared in the following manner:

. Arainine urocanate

- Introduce into a reactor fitted with a reflux device 720 g of methanol, 135 g of distilled water, and add with stirring 69 g of urocanic acid and 87 g of arginine.

- Slowly heat the reaction mixture, continue heating until reflux; maintain agitation until complete precipitation.

- Cool the mixture, then centrifuge and dry (Yield: around 90%).

. Ultraviolet spectrum (distilled water): maximum 267 nm

. pH (distilled water): 7.4.

. Histidine urocanate previously described

- Introduce into a reactor fitted with a reflux device 720 g of methanol, 135 g of distilled water and add, with stirring, 69 g of urocanic acid and 78.57 g of histidine.

- Slowly heat the reaction mixture, continue heating until reflux; maintain agitation until complete precipitation.

- Cool the mixture, then centrifuge and dry (Yield: around 90%)

. Ultraviolet spectrum (distilled water): from 260 to 268 nm.

Following are a series of examples of compositions in the form of a soluble amorphous powder making it possible to produce hydrosolutes in distilled water at various concentrations having biocompatible pHs for example between 6 and 7.5.

EXAMPLE 12 of a composition

Histidine ribonucleate 31.65

Histidine hydrochloride 18.33 Partial lyophilized collagen hydrolyzate 50.02

Ultraviolet spectrum (distilled water) from 260 to 268 nm, depending on the nature of the collagen pH

6.0-6.8.

EXAMPLE 13

Composition in amorphous powder form

Histidine ribonucleate Cytidine / uridine Histidine hydrochloride

31.65 16.65 18.33

Dehydrated collagen hydrolyzate 33.37

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EXAMPLE 14

EXAMPLE 15

EXAMPLE 16

EXAMPLE 17

Composition

Composition

Composition in amorphous powder form

Histidine ribonucleate 47.83

Sodium ribonucleate 8.15

Arginine urocanate 16.66

Uridine / cytidine 1.32

Dehydrated collagen hydrolyzate 26.04

amorphous powder form

Arginine ribonucleate 26.00

Histidine urocanate 15.63

Arginine hydrochloride 1.03

Histidine hydrochloride 24.67

Dehydrated collagen hydrolyzate 17.02

Uridine / cytidine 16.65

amorphous powder form

Histidine ribonucleate 31.65

Histidine 18.33

Arginine urocanate 16.65

Uridine / cytidine 16.65

Dehydrated collagen hydrolyzate 16.72

Composition in amorphous powder form

Histidine ribonucleate 31.65

Histidine 18.33

Arginine urocanate 16.65

Lyophilized collagen hydrolyzate 33.37

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EXAMPLE 18

Composition in amorphous powder form

Arginine ribonucleate

37.50

Arginine urocanate

35.67

Histidine urocanate

20.00

Glutathione

1.25

L-tyrosine

3.00

L-phenylalanine

0.50

L-tryptophan

0.75

L-histidine CLH

1.33

pH in distilled water = 6.5-7

EXAMPLE 19

Composition in amorphous powder form

Arginine ribonucleate 37.50

Arginine urocanate 35.67

Histidine urocanate 20.00

Glutathione 1.25

L-tyrodise / L-phenylalanine / L-tryptophan 4.25

Histidine hydrochloride 1.33

EXAMPLE 20

Composition in amorphous powder form

Adenosine 0.04

Guanosine 0.04

Inosine 0.04

Cytidine 0.04

Uridine 0.04

Glucose 9.40

Arginine urocanate 15.00

Lyophilized blood plasma hydrolyzate 75.04

EXAMPLE 21

Sodium ribonucleate 20.00

CMP, arginine 1.70

GMP, histidine 1.70

UMP, sodium salt 1.00

Glucose 2.50

Keratin hydrolyzate 73.10

The basic compositions constitute compositions of cyto-photo-protective agents of the invention

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and can be incorporated as active ingredients in doses of between 0.01% and 5%, exceptionally + 10% and preferably 0.10-3% in dermatological, cosmetological and dermal preparations pharmaceutical, to form cosmetic or dermo-pharmaceutical compositions according to the invention.

This incorporation is carried out in an extremely simple manner, usually by dissolving in the aqueous phase of these preparations, at temperatures between 20 ° C and 70 ° C.

Any type of usual excipient can be used for such cosmetic or dermo-pharmaceutical compositions containing water. They can be aqueous lotions, aqueous gels, emulsions, ointments, creams, ointments, presentation in capsules, capsules.

In addition, these active ingredients can be incorporated into liposomes, micelles and other forms of microencapsulation to accelerate or delay penetration.

An example of the preparation of a cosmetic and / or dermo-pharmaceutical-pharmaceutical composition containing one of the abovementioned compositions forming the subject of the invention is given below.

It is understood that the same can be done with the other compositions.

For example, the composition according to Example 13 is incorporated at a dose of 1% in the following emulsion:

EXPERIMENTAL RESULTS

In order to illustrate and demonstrate the advantages of the biological photo-protective agents according to the invention, experimental work has been carried out on them, compared with conventional photo-protective agents, aimed at:

- on the one hand to assess their own cyto-toxicity,

- on the other hand their cyto-photo-protective power in contact with the cells.

Thus the results obtained for some compounds cited in the examples of the preceding pages are grouped in the following three tables.

It should be noted that, from the point of view of the cutaneous photo-protection capacity of these compounds compared to the SCHULTZE methods or variants based on the MED, therefore the irradiation dose for the appearance of a limited erythema, the sun protection forces obtainable, would be in low to medium indices.

On the other hand, from the point of view of appreciation of cyto-photo-protection by in vitro contact, the cyto-photo-protective agents, subject of the present claims, are devoid of cyto-toxicity at useful concentrations and exert a real cyto- solar and essentially UV-B photo-protection, at radiation levels normally tolerable by each user, sator, in relation to their MED.

It should also be noted that a comparative test carried out with a sodium salt of deoxyribonu-cleic acid does not provide significant cyto-photo-protection. It is therefore surprising and quite not obvious to those skilled in the art that the organic derivatives of ribonucleic acid according to the invention have on the other hand a cyto-photo-protective effect.

- It is also known that UV-B causes morphological and functional degradation of Langerhans cells, and it is known that common sunscreens, cinnamate type, PABA do not prevent this degradation.

- Similarly, it is known that UV-B causes a fall in the ATP-asic activity of Langerhans cells, and that this degradation cannot be prevented by the aforementioned sun filters.

- These same filters have no action to ensure the protection of Langerhans cells against degradation and negativation of the response to the immunological test to DNFB by UV-B.

Propylene glycol stearate SE Paraffin oil Stearin

Stearyl alcohol Glycerin Carbomer 934 Triethanolamine Preservative Distilled water

1.00 7.70 1.50 0.40 4.00 0.10 0.80 qs qs 100.00.

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PROTOCOL type I

LD50 on MRC5 fibroblasts, in vitro

. The Fibroblast MRC5 cells are seeded on EMEM medium, supplemented with fetal calf serum (5%).

. 24 h later, the medium is replaced by a saline solution (PBS) of the product to be tested (in the case of PMCEH and PABEH filters, a mother solution is prepared).

. A sufficient number of dishes is prepared, by introducing increasing dilutions of the test substance (from 0.01% to 0.03%), so as to carry out a range of explorations.

. All dishes are then incubated at 37 ° C for 2 h.

. The saline solution is then replaced by the usual growth medium (EMEM + 5% FCS). . 72 h later, the cell cultures are stained.

. The number of living cells is evaluated by measuring the intensity of coloring of each dish with the Electronic Image Analyzer.

. The LD50 corresponds to the just sufficient dose of test product, inhibiting the cell growth rate by 50%, compared to the control.

PROTOCOL type II

MRC5 fibroblast toxicity

. The MRC5 cells are seeded on conventional culture medium.

. 24 h later, brought into contact with the product to be tested, previously dissolved in PBS.

. Then the solution is replaced by the growth medium = EMEM + 5% SVF.

. 3 days later, the growth rate is evaluated:

- by measuring the coloration with the Electronic Image Analyzer or

- by measuring the intracellular ATP level.

PROTOCOL type III

LD50 on epidermal keratinocytes, in vitro

. The isolated epidermal keratinocytes are cultured on dishes (culture of the 1st explantation) in DMEM medium at 10% FCS.

. 24 h later, the previous culture medium is replaced by a saline solution enriched in amino acids (= DMEM) of the product to be tested.

. A sufficient number of dishes is prepared so as to make a range of increasing dilutions of the test substance.

. All dishes are incubated at 37 ° C for 3 days.

. Then, the intracellular adenosine triphosphate * is extracted and dosed in each box, by bioluminescence technique.

. The toxicity of each substance studied is estimated as a percentage, compared to the control medium (DMEM).

. The lethal dose (LD50) is determined graphically, as being the minimum dose of product which reduces the ATP level by 50% compared to the control.

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STUDY OF DLso CYTOTOXICITY

REFERENCE

Ex. No.

MRC 5 fibroblasts in culture (in vitro)

Epidermal keratinocytes in culture (in vitro)

DLso in g%

Standard Protocol

DUo in g%

Standard Protocol

Ethyl 4-methoxycinnamate-2-hexyl (PMCEH)

0.015

I

0.038

III

Ethyl 2-hexyl 4-dimethylaminobenzoate (PABEH)

<0.01

I

0.014

III

Potassium ribonucleate

1

> 1

II

> 2

III

Arginine ribonucleate

3 A

> 2

II

> 2

III

Histidine ribonucleate

3 B

> 2

II

> 2

III

ATP, Na

4 E

> 0.5

II

0.2

III

Cytidine histidine monophosphate

7 B

1

II

0.76

III

Inosine

8 C

> 2

II

> 2

III

Composition, Ex. 13

13

> 3

11

> 2

III

Composition, Ex. 18

18

1.2

II

1.25

III

16

O) o en en

Ol o

45 ”. in

4 *. o

G) in fo in

IV) o

STUDY OF CYTOTOXICITY on LANGERHANS CELLS (L.C.)

REFERENCE

Ex.

0

not

Concentration

X

Cytotoxicity as a percentage of L.C. destroyed

Standard protocol

. Cytotoxicity on L.C. is evaluated in the form of a percentage of the number of negativated cells relative to the initial number of L.C. HLADR + in the presence of the test substance.

. This test is carried out on a suspension of L.C. from an immediately treated epidermal biopsy, given the difficulties in cultivating L.C.

CALCULATION of CYTOTOXICITY (see Protocol V)

N-lot 1 - N-lot 3

- - - x 100

Ethyl 4-methoxycinnamate-2-hexyl (PMCEH)

0.03

79 - 80%

V

Ethyl 2-hexyl 4-dimethylaminobenzoate (PABEH)

0.01

35%

V

Potassiun Ribonucleate

1

1

17%

V

Arginine ribonucleate

3 A

1

32%

V

Histidine ribonucleate

3 B

5

? y.

V

ATP, Na

4 E

0.2

10%

V

Cytidine histidine monophosphate

7 B

0.5

34 y.

V

lnosine

8 C

1

33%

V

Composition, Ex. 13

13

3

32 y.

V

Composition, Ex. 18

, 8

0.5

6%

V

N-lot 1

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PROTOCOL IV

Evaluation of the photo-protective power of substances in contact with firbroblasts MRC5

. The aim of this study is to assess the photoprotective capacities of various substances on the growth of MRC5 fibroblasts, in in vitro culture, when they are irradiated by a UVB source.

. The cells are seeded at a low rate.

. 24 hours later, the MRC5 cells are covered with a solution of the substance to be studied in PBS, then irradiated with a defined dose (in mJ / cm2) of UVB.

. Then the saline solution is replaced by the EMEM growth medium + 5% FCS.

. 72 hours later, the cell cultures are stained, and the growth rate is evaluated by Electronic Image Analysis.

PROTOCOL type V

Study of the cyto-photo-protective power of substances in contact with Langerhans cells.

Microscopic enumeration of Langerhans HLA-DR + cells

. From a skin biopsy, a suspension of epidermal cells is prepared.

. This cell suspension is divided into 2:

1 / part serves as a control, added only with PBS buffer

a) 1st batch not irradiated

b) 2nd batch irradiated by UVB (x mJ / cm2)

2 / the other party receives the substance to be studied in solution in PBS buffer:

a) 3rd batch not irradiated

b) 4th batch irradiated with UVB (x mJ / cm2)

. The aforementioned 4 batches of epidermal cells containing the Langerhans cells are then labeled by immunocytochemistry (labeling of the HLA-DR specific antigenic sites of the Langerhans cells).

. For each of the 4 batches, the HLA-DR cells are then counted by microscopic counting.

. Results:

- the 1st batch: Corresponds to the initial number of intact L.C. (control) HLA-DR + per unit of volume.

- the 2nd batch: irradiation at a determined dose of UVB results in a reduction in the initial number of

L.C.-HLA-DR + per unit of volume

The remaining number of L.C.-HLADR + = N-lot 2.

- the 3rd batch: the substance presumed to be photo-protective for L.C. can possibly exert a specific cytotoxicity at a given concentration. The value used is that of the remaining number of L.C.-HLADR + per unit of volume in contact with the substance at the concentration studied. The corresponding number L.C.-HLADR + = N-Lot 3.

- the 4th batch: used to determine the number of L.C.-HLADR + in contact with the test substance at a concentration identical to the 3rd batch and after UVB irradiation at the same dose as the 2nd batch. The number of L.C.-HLADR + remaining per unit of volume = N-Lot 4.

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STUDY OF CYTOPHOTOPROTECTION IN CONTACT

REFERENCE Ex. Lanqerhans cells not included - MRC 5 Fibroblasts in culture n ° pension HLA-DR + SITES (in vitro) (in vitro)

Concen- Cyto- Power Protocol Concen- Cyto- Protocol Protocol photoprotective tration photoprotective tration type * *

Ethyl 4-methoxycinnamate-2-hexyl (PMCEH)

0.03%

0

V

0.03%

1.8% NS

IV

Ethyl 4-dimethylaminobenzoate-2-hexyl

(PABEH)

0.01% 0.03%

+ 8% 0

V

0.02%

0

IV

Potassium ribonucleate

1

1%

+ 100%

V

1%

100%

IV

Arginine ribonucleate

3A

1%

+ 65%

V

0.3%

58%

IV

Histidine ribonucleate

3B

5%

+ 100%

V

0.5%

96%

IV

ATP, Na

4E

0.2% 1%

+ 47% + 100%

V

V

0.50%

46%

IV

Cytidine histidine monophosphate

7B

0.5%

+ 24%

V

0.12%

77%

IV

Inosine

8C

1%

+ 100%

V

1%

74%

IV

Composition, Ex. 13

13

3%

+ 53%

V

2.70%

99%

IV

Composition, Ex. 18

18

0.5%

+ 81%

V

0.50%

100%

IV

Claims (34)

Claims 1. Use of a compound chosen from the group of nucleic acid compounds and derivatives mentioned below: A) ribonucleic acids and their salts with mineral or organic bases, B) ribonucleotides as well as their salt type derivatives, with mineral or organic bases: and C) ribonucleosides for the preparation of medicaments for the photo-protection of skin cells, in particular Langerhans cells. 2. Use of a compound chosen from the group of nucleic acid compounds and derivatives mentioned below: A) ribonucleic acids and their salts with mineral or organic bases, B) ribonucleotides as well as their salt type derivatives, with mineral or organic bases: and C) ribonucleosides for the preparation of cosmetic compositions for the photo-protection of skin cells. 3. Use according to one of claims 1 or 2, characterized in that one does not use a synthetic cyto-toxic sunscreen of the cinnamate or PABA type or their derivatives. 4. Use according to one of claims 1 to 3, characterized in that at least one compound is chosen from the group of complex salts of ribonucleic acids with basic proteins, basic amino acids or basic peptides and complex salts of ribonucleotides with basic proteins, basic amino acids or basic peptides. 5. Use according to one of claims 1 to 3, characterized in that the ribonucleic acids are in the form of their salts with mineral bases or with organic bases. 6. Use according to claim 5, characterized in that the ribonucleic acids are in the form of their salts with NaOH, KOH, NH4OH or an ethanolamine. 7. Use according to one of claims 1 to 3, characterized in that the ribonucleic acids are in the form of their salts or complexes with - histones or microproteins of molecular weight between 11,000 and 24,000, or - globins whose molecular weights are between 15,000 and 70,000. 8. Use according to one of claims 1 to 3, characterized in that the ribonucleic acids are in the form of their complex salts with L-histidine, L-arginine, L-lysine, L-ornithine, or L-hy-droxylysine . 9. Use according to one of claims 1 to 8, characterized in that the ribonucleotides are chosen from the group of natural monoribonucleotides. 19 5 10 15 20 25 30 35 40 45 50 55 CH 682 453 A5 10. Use according to one of claims 1 to 8, characterized in that the ribonucleotides are chosen from the group AMP, ADP, ATP, GMP, GDP, GTP, CMP, CDP, CTP, UMP, UDP, UTP, IMP, IDP, ITP, XMP, XDP and XTP. 11. Use according to claim 9 or 10, characterized in that the ribonucleotides are used in the form of their salts with bases, which makes it possible to obtain pHs of 5.8 to 8 which are biocompatible. 12. Use according to claim 11, characterized in that the ribonucleotides are used in the form of their salts with NaOH, KOH, NH4OH, or with organic bases, or with an ethanol-amine. 13. Use according to claim 11, characterized in that the ribonucleotides are used in the form of their salts with: - histones or microproteins of molecular weight between 11,000 and 24,000, - globins or protein copulas of hemoglobins and myoglobins whose molecular weights are between 15,000 and 70,000. 14. Use according to claim 11, characterized in that the ribonucleotides are used in the form of their salts with L-histidine, L-arginine, L-lysine, L-ornithine and L-hydroxylysine. 15. Use according to claim 11, characterized in that the ribonucleotides are used in the form of their salts with basic peptides. 16. Use according to one of claims 1 to 15, characterized in that the ribonucleosides are chosen from the group of natural monoribonucleosides. 17. Use according to one of claims 1 to 15, characterized in that the ribonucleosides are chosen from the group adenosine, cytidine, guanosine, inosine, uridine and xanthosine. 18. Use according to one of claims 1 to 15, characterized in that the ribonucleosides used are associated or combined with one or more of the nucleoproteins or ribonucleotides or their salts in proportions for obtaining biocompatible pH between 5.8 and 8. 19. Use according to one of claims 1 to 18, characterized in that additional use is made of derivatives of urocanic acid or urocanoprotides in the form of simple or complex salts of urocanic acid or acid derivatives urocanic with proteins, peptides, amino acids. 20. Use according to claim 19, characterized in that the derivatives of urocanic acid or urocanoprotides in the form of complex salts are obtained by a combination of urocanic acid with: a) basic proteins; b) ribonucleotides; c) basic peptides, d) basic amino acids, taken alone or in combinations. 21. Use according to claim 20, characterized in that urocanic acid is combined with histones or globins, AMP, ADP or ATP, L-histidine, L-arginine, L-lysine, L-hydroxylysine and L-ornithine. 22. Use according to claim 20, characterized in that the derivatives of urocanic acid are complexes of urocanic acid with histones, peptides, basic amino acids and nucleotides, which are more cytophilic than the derivatives or salts alkaline or alkaline earth minerals. 23. Use according to one of claims 1 to 22, characterized in that one uses additonnelle-ment amino acids and peptides or proteins. 24. Use according to claim 23, characterized in that the aforementioned amino acids and peptides and proteins are chosen from: A) one or more of the following amino acids: . L-histidine, L-arginine, L-lysine, L-citrulline, L-ornithine and L-hydroxylysine, . L-tyrosine, L-phenylalanine and L-tryptophan, L-glutamic, L-aspartic acid, L-proline, L-hydroxy-proline, . glycine, aianine, L-valine, L-leucine, L-isoleucine, . L-serine and L-threonine, . L-glutamine and L-asparagine, . L-cysteine, L-methionine and cystine, ß) one or more of the peptides and proteins which are naturally present in the cells and / or peptides resulting from the acid, basic or enzymatic hydrolysis of polypeptides and / or proteins, scleroproteins and soluble proteins. 25. Use according to claim 24, characterized in that the peptides and proteins are chosen from: - silk fibroin in a concentration of 1 to 10% - collagen in concentration from 1 to 10% - elastin in concentrations of 1 to 10% - hydrophilic keratins - histones in concentrations of 0.1 to 10% 20 5 10 15 20 25 30 35 40 45 50 55 60 65 CH 682 453 A5 - globins, for example hemoglobins and myoglobins, in a concentration of 0.1 to 10% - plasma proteins, for example serum albumin, serum globulin, in a concentration of 0.1 to 10% - plasma proteins partially hydrolyzed by the enzymatic route, ie blood plasma rich in proteins, around 8%, in a concentration of 0.1 to 10%. 26. Use according to one of claims 1 to 25, characterized in that the concentration of the compound for protecting the cells is between 0.01% and 10%, by weight relative to the total weight of the drug or of the cosmetic composition . 27. Use according to claim 26, characterized in that the concentration is between 0.01% and 3%, by weight. 28. Compound, chosen from the group comprising simple or complex salts of ribonucleotides with organic bases, chosen from basic proteins and basic peptides. 29. Compound according to claim 28, characterized in that the protein is histone or globin, and the peptide is glutathione. 30. Compound according to claim 28 or 29, characterized in that the ribonucleotides are chosen from the group AMP, ADP, ATP, GMP, GDP, GTP, CMP, CDP, CTP, UMP, UDP, UTP, IMP, IDP, ITP , XMP, XDP and XTP. 31. Dermo-pharmaceutical composition comprising a compound chosen from the group comprising: A) the simple or complex salts of ribonucleic acids with organic bases, chosen from basic proteins, and B) the simple or complex salts of the ribonucleotides with organic bases chosen from basic proteins and basic peptides, in a pharmaceutically compatible excipient, vehicle or support. 32. Cosmetic composition comprising a compound chosen from the group comprising: A) the simple or complex salts of ribonucleic acids with organic bases, chosen from basic proteins, and B) the simple or complex salts of the ribonucleotides with organic bases chosen from basic proteins and basic peptides, in a cosmetically compatible excipient, vehicle or support. 33. Composition according to claim 31 or claim 32, characterized in that the concentration of the mentioned compound is from 0.01 to 10% relative to the weight of the composition. 34. Composition according to one of claims 31 to 33, characterized in that the protein is histone or globin and the peptide is glutathione. 21