MXPA99008998A - Cosmetic and/or dermatological composition containing a derivative of methylated silanol and a derivative of hydrolysed plant protein - Google Patents

Abstract

The invention relates to a dermatological and/or cosmetic composition for treating symptoms of skin ageing comprising a combination of at least one derivative of methylated silanol and at least one derivative of hydrolysed plant protein. More particularly, the derivative of methylated silanol is methylsilanol mannuronate and the derivative of hydrolysed plant protein is an extract of hydrolysed wheat protein. The composition can also further contain (a) vitamin C and/or one or a plurality of its derivatives, for example magnesium ascorbyl phosphate, (b) vitamin E and/or one or a plurality of its derivatives and/or, (c) vitamin A and/or one or a plurality of its derivatives and/or, (d) oligopeptides or their derivatives and/or, (e) vegetable oils extracted from Helianthus annuus and/or Hedera helix and/or, (f) phytic acid.

Description

COSMETIC AND DERMATOLOGICAL COMPOSITION THAT CONTAINS A METHYLED SILANOL DERIVATIVE AND A DERIVATIVE OF HYDROLYZED VEGETABLE PROTEIN The invention relates to the treatment of the skin for example to treat the symptoms of skin aging by preventing irreversible crosslinks of connective tissue proteins and to minimize the effects of air pollution.

Aging is a natural process which results from the progressive decay of the function of an organism. During aging, extensive modifications occur in each organ, particularly in the connective tissue.

For example, collagen, the most abundant protein in the human body, begins to become more insoluble, more resistant to digestion, thermal breakdown and mechanical stress. In the case of aging of the skin, these modifications of the physicochemical properties of collagen contribute to the development of long-term complications, such as loss of elasticity, flexibility and normal elastic tension.

Collagen is a fibrous protein composed of three polypeptide chains (tropocollagen filaments) wound in a triple helix. These polypeptide chains are equal in length and each of these chains has approximately one thousand amino acid groups. These mainly contain residues with 35 percent glycine, 21 percent proline, 12 percent hydroxyproline and 11 percent alanine.

-X-ray diffraction analysis has shown that each polypeptide chain of tropocollagen itself forms a triple helix. These also have cross-links between these formed by hydrogen bonds and an unusual type of covalent bond, which is only found in collagen (formed between the two-chain lysine residues). Tropocollagen also contains carbohydrate side chains attached to hydroxylysine hydroxyl groups.

The synthesis of collagen molecules within the cell in a complex process and requires major post-translational changes intracellular and extracellular. In the intracellular space, during biosynthesis, some lysine and proline residues are hydroxylated, and these hydroxylated residues are glycosylated by means of an enzyme. "Glycosylation" 'means the bond of a sugar having six carbon atoms with the free amino group of a protein. The link is also known in the art with the name glycosylation or glycation. These reactions of hydroxylation and glycosylation of the tropocollagen are necessary for them to be secreted out of the cell. Once secreted into the extracellular space, the tropocollagen chains are joined with covalent bonds and form fibrillar networks with cross-links.

In addition to the enzymatic glycosylation of the tropocollagen amino acid groups, non-enzymatic glycosylation of certain lysine and hydroxylysine residues in the extracellular space may also occur. In fact, the nonenzymatic addition of any sugar that has six carbon atoms to the free amino acid groups of the protein causes structural and functional modifications of the tissue. In the case of collagen, this causes the formation of irreversible cross-links between the collagen fibers, which ultimately cause a hardening of the tissue and a loss of elasticity of the skin (Cerami et al 1987).

The non-enzymatic glycosylation of proteins and their chemical consequences have been known for a long time, and in reference to the so-called Maillard or Browning reactions of sugars in food chemistry. These reactions cause the condensation of a glycoaldehyde or a ketone with a free amino group of a protein, producing a glycosylamine (base - Schiffs). The resulting product may undergo a rearrangement Amadori to form the most stable Amadori product. This product can then start a series of dehydrations and rearrangements to form highly reactive carbonyl compounds identified by their fluorophoric and chromophoric properties. The fluorophores and chromophores that result from these chain reactions have been designated by the names of end products developed in the glycosylation (EPEG) of developed Browning products or Maillard products (in food chemistry). The reactive carbonyl groups of EPEG are capable of forming irreversible bonds with other amino groups of the protein, increasing the decrease in solubility of the protein, which is one of the causes of the aging process (Ceramide et al 1987, Brownlee et al 1986, Shin et al 1988).

The prevention of the formation of irreversible bonds between collagen fibers by non-enzymatic glycosylation is the goal of all "anti-aging" treatments. One of the methods used is to inactivate the glycosylation products at any previous stage (the Schiff base and the addition products resulting from an Amadori arrangement) by blocking their reactive carbonyls groups. In this field, some investigations have been carried out with a nucleophilic hydrazine compound, aminoguanidine (Cerami, et al 1987, Brownlee et al 1986) and its derivative, guanobenzoacetate (Igaki et al 1991). Another experiment focused on preventing the formation of links between proteins in connection with anti-aging treatment consists in removing the EPEG products by activating microphages (Cerami et al, 1987).

Currently the skin is exposed to air pollution in the form of, for example, emissions from motor vehicles or tobacco smoke. These emissions can cause a reduction in the moisture of the skin and can cause undesirable dermatological effects. Therefore there is a need for dermatological and cosmetic compositions that prevent the adverse consequences of exposure to air pollution. The present invention proposes the provision of dermatological and cosmetic compositions.

This invention is mainly related to the combination of methylated silanol derivatives with hydrolyzed vegetable protein derivatives to prevent the consequences of skin aging symptoms to avoid irreversible links of connective tissue proteins and to prevent the consequences of exposure to atmospheric pollution.

The invention therefore relates to the dermatological and cosmetic composition for treating the symptoms of skin aging and for preventing the consequences of exposure to atmospheric pollution comprising a combination of at least one methylated silanol derivative and at least one derived from hydrolyzed vegetable protein.

Another objective of this invention is the use of the combination of methylated silanol derivatives, the hydrolyzed vegetable protein extract, and vitamin C (and / or) its derivatives, particularly ascorbyl magnesium phosphate to prevent the consequences of the aging symptoms of the skin by stimulating the synthesis of new collagen and by maintaining the degree of glycosylation in the collagen synthesized again at a constant value and preventing the consequences of exposure to atmospheric contamination.

Therefore the invention also relates to a dermatological and cosmetic composition as mentioned above and which also contains vitamin C and / or one or a plurality of its derivatives.

-The compositions of the present invention which additionally contains extracts of oils from vegetable sources such as Helianthus annus and Hederá helix and / or phytic acid for example extracted from rice bran which has particular utility in the treatment of the consequences of exposure to the atmospheric pollution.

Therefore the present invention also relates to a dermatological and cosmetic composition as mentioned above and which also contains extracts of oils from plant sources such as Helianthus annus and Hederá helix and / or phytic acid for example extracted from rice bran.

The compositions of the present invention additionally contain at least one oligopeptide or derivative thereof that provides additional antiglycation properties. Suitable oligopeptides or derivatives thereof include the palmitoyl oligopeptide wherein the oligopeptide is comprised with glycine, histidine and lysine or arginine radicals, glycine aspartic acid and serine radicals.

The present invention therefore also relates to a dermatological and cosmetic composition as mentioned above which also contains an oligopeptide or a derivative thereof.

Another object of this invention is the use of the combination of methylated silanol derivatives, the extract of hydrolyzed vegetable proteins (particularly the extract of hydrolyzed wheat proteins), vitamin C (and / or its derivatives, particularly ascorbyl magnesium phosphate), and vitamin E (and / or skin by inhibiting the production of free radicals).

The invention therefore also relates to a dermatological and cosmetic composition comprising one or a plurality of methylated silanol derivatives, an extract of hydrolyzed vegetable proteins (particularly a hydrolyzed wheat protein extract), vitamin C (and / or its derivatives, particularly ascorbyl magnesium phosphate), and vitamin E (and / or derivatives).

In particular, the compositions of this invention, which are judged useful for the treatment of the symptoms of aging for the prevention of the consequences of exposure to atmospheric pollution, are constituted by the combination of two or more of the anti-aging agents. above-mentioned glycosylation, vitamin C and / or its derivatives, and optionally, vitamin E and / or its derivatives, and vitamin A and / or its derivatives and / or extracts of oils from vegetable sources such as Helianthus annus and Hederá helix and / or phytic acid for example extracted from rice bran.

With respect to this, the invention relates to a dermatological and cosmetic composition as previously defined and which further contains vitamin E and / or one or a plurality of its derivatives, or vitamin A and / or one or a plurality of Their derivatives.

The invention also relates to the local or topical application of the composition of the invention as well as to a method for treating the symptoms of skin aging, which consists of applying locally to the skin and for the prevention of consequences of exposure to air pollution in the body areas of a mammal to be treated, an amount of one of the aforementioned compositions.

The invention also relates to the use of the aforementioned compositions as a medicinal product and to the use of these compositions for the preparation of a medicinal product for the treatment of the symptoms of skin aging and for the prevention of the consequences of the exposure to air pollution.

Other advantages and features of the invention will be understood more clearly with the following description and in reference to the -figures here: Figure 1 provides the anti-glycation activity of methylsilanol mannuronate (Algisium C), Figure 2 provides "the anti-glycosylation activity of a hydrolyzed wheat protein extract (Integrissyma), Figure 3 provides the anti-glycosylation activity of the combination of methylsilanol mannuronate (Algisium C) and an extract of the protein of hydrolyzed wheat (Integrissyma), Figure 4 provides the effect of various dermatological compositions on collagen synthesis by cultures of human fibroblast cells, and Figure 5 provides the effect of various dermatological compositions of collagen glycosylation produced by cultures of human fibroblast cells.

Detailed Description of the Invention Methylated Silanol Derivatives Various compounds can be used as methylated silanol derivatives, which include the following compounds, - the contiguous list is not complete: methylsilanol sodium mannuronate (Algisium, Exsymol) methylsilanol manure (Algisium C®, Exsymol) Nilon-12 methylsilanol manureate ( Algisium C powder®, Exsymol) ascorbylmethylsilanol (C® Ascorbosilane concentrate, Exsymol) Ascorbylmethylsilanol pectinate (Ascorbosilane C®, Exsymol) dimethyloxobenzosilane (DSBC®, Exsymol) Nylon-12 dimethyloxobenzosilane (DSBC powder®, Exsymol) Dimethylsilanol sodium hyaluronate (DSH®, Exsymol) Dimethylsilanol Hyaluronate (DSHC®, Exsymol) Methylsilanol glycyrrhizinate (Glysinol®, Exsymol) M-tilanylhydroxyproline (Hydroxyprosilane®, Exsymol) Methylsilanehydroxyproline Aspartate (Hydroxyprosilane C®, Exsymol Methylsilanol sodium lactate (Lasilium®, Exsymol) Elastinate of lactoylmethylsilanol (Lasilium C®, Exsymol) Dioleyl tocopheryl methylsilanol (Liposiliol C®, Exsymol) Methylsilanol acetylmethionate (Methiosilane®, Exsymol) Elastinate of acetylmethionylmethylsilanol (Metiosilane C®, Exsymol) Methylsilanol Glycerylcocoate PEG 7 (Monosiliol®, Exsymol) Methylsilanol Triglycerylcocoate PEG 7 (Monosiliol C®, Exsymol) Methylsilanol elastinate (Proteosilane C®, Exsymol) Pyrrolidone caustic carboxylate of methylsilanol (Silhydrate®, Exsymol) Pyrrolidone cuprous carboxylate of methylsilanol (Silhydrate®, Exsymol) Methylsilane-1-carboxymethyl-teeophylline (Theophillisilane®, Exsymol) Methylsilanecarboxymethylteophylline alginate (Theophillisilane C®, Exsymol) Methylsilanolacetyl tyrosine (Tyrosine®, Exsymol) or Methylsilanol acetyl tyrosinate copper (Tyrosilane C®, Exsymol) Among the preferred methylated silanol derivatives in the context of this invention are Methylsilanol sodium mannuronate, Methylsilanol manuronate, Ascorbylmethylsilanol, Ascorbylmethylsilane pectinate, Methylsilanol hydroxyproline, Methylsilanol hydroxyproline aspartate, or Methylsilanelacetyltyrosine.

A particularly preferred derivative of methylsilanol is methylsilanol mannuronate.

The ethylsilanol derivatives identified above are commercially available from indicated sources. For example, methylsilanol manuronate is commercially available from Exsymol under the trademark of Algisium C.

This commercial product is an aqueous solution containing 1% methylsilanol mannuronate.

The amount of the commercial product contains the methylated silanol derivative which may be included in the formulations of the present invention generally ranges from 1 to 20 weight percent, the normally preferred concentrations being in the range between 2 and 7 weight percent of the total weight of the composition. The compositions will therefore contain 0.01 to 0.2%, preferably 0.02 to 0.07%, of the methylated silanol derivative.

Derivatives of hydrolyzed vegetable proteins Various protein derivatives of hydrolyzed plants, more particularly proteins of hydrolyzed plants of cereal origin (eg, barley, wheat, oats) in combination with the methylated silanol derivative can be used to form the compositions of the invention. The choice of the derivative can easily be made by a person skilled in the art. These products include extracts of wheat proteins hydrolyzed by an enzyme and containing two peptide groups of different molecular weights.

Suitable derivatives of hydrolyzed vegetable proteins are commercially available. For example, a hydrolysed wheat protein is commercially available under the trademark of Intergrissyme. This commercial product is an aqueous preparation containing (20%) of hydrolyzed wheat protein (5%) of polysorbate 20 and (5%) of glycerin.

The amount of the commercial product containing the hydrolyzed vegetable protein generally varies between 0.25 and 5 weight percent of the total weight of the composition, the preferred concentrations have a range between 0.5 and 3 weight percent. The compositions will therefore contain 0.05 to 1%, preferably 0.1 to 0.6% hydrolyzed vegetable protein.

Vitamin C Vitamin C and its derivatives have an effect on the synthesis and secretion of collagen outside the cells. In this process, vitamin C has main functions: (1) vitamin C is the cofactor of the two enzymes, lysyl and prolyl hydroxylase, which are responsible for the formation of hydroxylation of tropocollagen aimed at initiating its secretion out of the cell (Freiberger et al 1980, Murad et al 1981 and 1983, Tajima and Pinnell 1982). (2) Vitamin C controls the duplication of three genes (proai, proa2, and proa3) placed - in different chromosomes to initiate collagen biosynthesis (Pinnell et al 1987).

The combination of vitamin C and its derivatives (eg, magnesium ascorbyl phosphate) with the composition of the invention can further improve the anti-glycosylation agents to improve the anti-aging treatment method, since, with these compounds, it is It is possible to stimulate the synthesis of connective tissue collagen while protecting these against non-enzymatic glycosylation.

It has been demonstrated by means of in vitro biochemical tests and cell culture tests that the use of a combination of the aforementioned compounds particularly methylsilanol manuronate, hydrolyzed vegetable proteins and, optionally, magnesium ascorbyl phosphate, in an aqueous solution or in creams with the effective amount to treat the symptoms of skin aging.

Hydrolyzed vitamin C or ascorbic acid can be extracted from plants or chemically synthesized. It has relatively high power and, in aqueous solution, is very sensitive to oxidation in the presence of molecular oxygen, alkalis, metals and under certain pH conditions. This is because it is preferred when this substance is used in its molecular form, that is in acidic conditions of pH preferably between 2.5 and 4.

In addition, there are also more stable derivatives of the substance, such as ascorbyl salts or ascorbyl esters and the encapsulated forms of vitamin C: magnesium ascorbate (Vitacedone® UCIB) or magnesium ascorbyl phosphate (Nikkol VC-PMG®, Jan Dekker) or ascorbyl and sodium sulfate (Nikkol VC-SS®, Jan Dekker) or ascorbyl palmitate or acid polypeptide Ascorbic J (Vitazyma C®, Brooks) or ascorbylmethylsilanol pectinate (Ascorbilane®, Exsymol) or microspheres of which the wall is made of atelocollagen that encapsulates magnesium ascorbyl phosphate (Thallaspheres Coletica). Yes, for example, the magnesium ascorbyl phosphate is used, the pH of the aqueous phase is preferably between 7 and 8, for the stability of the substance in aqueous medium.

The use of at least one of the aforementioned forms of vitamin C or its derivatives or its encapsulated forms is effective in an aqueous solution or in a cream with an amount of 0.25 to 30 percent. If two or more different forms of vitamin C are used in combination, it is preferred that the total concentration of the compounds does not exceed 20 weight percent of the composition.

Vegetable extracts Plant sources from which suitable oils can be obtained include Helianthus annuus (sunflower) and Hederá helix. Phytic acid can be extracted from the rice bran. The compositions of the present invention may contain 0.005 to 0.05%, preferably 0.01 to 0.04%, of each of the oils are extracted from Helianthus annuus, the oil is extracted from the Hederá helix and the phytic acid is extracted from the rice bran. . An aqueous composition contains an extract of Helianthus annuus (3%), an extract of Hederá helix (2%) phytic acid from rice bran (2%), glycerin (40%), PEG-8 (15%), caprylyl glycol ( 4.5%), ether of PPG-1 / PEG-9 / lauryl glycol (3%), "butylene glycol (3%) and sodium polyacrylate (0.5%) is commercially available by Sederma under the trademark of Osmopur. used in the compositions of the present invention at a level of 0.5 to 2%, preferably about 1% of the total composition.

Oligopeptides and derivatives The oligopeptide or derivative is preferably palmitoyl oligopeptide. This material is present in commercially available materials such as: Bipéptido CL (Sederma) which contains glyceryl polymethacrylate, propylene glycol, and a palmitoyl oligopeptide wherein the olig-opeptide is composed of glycine, histidine and lysine radicals. FN biopeptide (Sederma) which contains glyceryl polymethacrylate, butylene glycol, and a palmitoyl oligopeptide wherein the oligopeptide is composed of arginine, glycine, aspartic acid and serine radicals. 7 Amadorin (Solavia) which is a polypeptide composed of arginine and lysine radicals. Citogard (Pentapharm) which is a polypeptide saccharomyse.

The amount of the commercial product (eg Biopeptide CL) which can be included in the formulations of the present invention generally ranges from 20 preferably 2 to 7% by weight of the total weight of the composition.

Vitamin E -Vitamin E and its derivatives can be used in various ways, the choice of this can be made without difficulty by the person experienced in the art. For example, DL-tocopherol tocopherol acetate is preferred The concentration of vitamin E in the compositions of this invention generally varies between 0.05 and 2% by weight of the total weight of the composition.

Vitamin A Vitamin A and its derivatives can also be used in various ways the choice of this can be made without difficulty by the person skilled in the art. For example, retinol, retinyl acetate, or retinyl palmitate are preferred.

The concentration of vitamin A in the compositions of this invention generally ranges from 0.02 to 1 weight percent of the total weight of the composition.

Formulation of the composition The combination of the aforementioned compounds can preferably be incorporated into a water-in-oil emulsion (including water-in-silicone oil emulsion), an oil-in-water emulsion or a water-in-oil-in-water multiple emulsion or a pseudo-emulsion (dispersion of two immiscible phases, an oily phase in an aqueous phase, using thickening agents).

Preferably, the compositions of this invention are in the form of any water-in-oil emulsion, an oil-in-water emulsion, or a water-in-oil-in-water multiple emulsion or a pseudo-emulsion. These emulsions or pseudoemulsions may comprise the following materials: (a) Oily phase The oily phase of the emulsions of this invention may contain, for example: hydrocarbon oils such as paraffin or mineral oils such as isohexadecane, natural oils such as sunflower oil, primrose oil, jojoba oil, hydrogenated castor oil, avocado oil or hydrogenated palm oil, natural triglycerides such as caprylic / capric triglyceride, caprylic / capric / linoleic triglyceride or caprylic / capric triglyceride / succinic, silicone oil such as cyclomethicone, dimethicone or dimethiconol, esters of fatty acids such as myristyl myristate or isopropyl myristate, alcohols, fatty acids such as hexadecyl alcohol or stearyl alcohol, waxes such as beeswax, paraffin wax, carnauba wax or ozokerite, lanolin and its derivatives (oil, alcohol, waxes), or mixtures of these.

Particularly preferred is the water-in-oil emulsion, or the oil-in-water emulsion or other medium comprising the composition of this invention, the aqueous phase represents from about 5 to about 30 percent, and preferably from about 10 to about 20 percent in weight of these compositions. (b) Emulsifiers Emulsifiers that can be used in the compositions of this invention can be selected from emulsifiers known in the art that can be used in water-in-oil or oil-in-water emulsions.

The water-in-oil and oil-in-water compositions can be prepared by using an emulsifier selected from among emulsifiers suitable for cosmetics including: sesquioleates such as sorbitan sesquioleate, emulsifiers based on silicon oil such as silicone polyols, sorbitan esters and ethoxylated sorbitan esters such as sorbitan stearate or polysorbate, glyceryl esters such as glycerate stearate or glyceryl isostearate, sucrose esters such as sucrose cocoate and sucrose distearate, ethoxylated fatty alcohols such as ethoxylated hexadecyl alcohol or ethoxylated stearyl alcohol, ethoxylated soy steels, or mixtures of the aforementioned emulsifiers.

The amount of emulsifier may be present in the oil-in-water, water-in-oil composition is preferably in the range of from about 0.5 to about 15 weight percent * of the composition. The amount of emulsifier that may be present in the water-in-oil-in-water multiple emulsion of this invention is preferably in the range of from about 7 to about 20 weight percent of the composition. (c) Other compounds of the formulation The compositions of this invention may further comprise one or more other compounds that are known to those skilled in the art, for example: electrolytes for stabilizing emulsions such as sodium chloride or magnesium sulfate or sodium citrate, preferably in an amount the range from about 0.2 to about 4 weight percent of the composition, humectants such as glycerin, propylene glycol, polyethylene glycol, (PEG) or sorbitol, preferably in an amount in the range from about 1 to about weight percent of the composition, thickeners such as xanthate gum, cellulose derivatives, carbomers, acrylic acid copolymers, sclerosum gum, preferably in an amount in the range of about 0.05 to about 1 weight percent of the composition, chelants such as tetrasodium EDTA, preferably in an amount in the range of about 0.01 to about 0.5 weight percent of the composition, softening agents such as fatty acid ether or fatty acid esters, preferably in an amount in the range from about 0.5 to about 10 weight percent of the composition, moisturizing agent such as D-panthenol, hyaluronic acid, sodium pyrrolidonecarboxylate, preferably in an amount in the range of about 0.01 to about percent by weight of the composition, film-forming agents to facilitate spraying on the surface of the skin, such as polymethacrylates, preferably in an amount in the range of about 0.05 to about 3 weight percent of the composition, blockers sunscreens such as methoxycinnamate, butylmethoxydibenzoylmethane, isoamyl methoxycinnamate, octyldimethyl PABA, octyl salicylate, benzophenone 3, octyl triazone, ethyl 4-polyethoxy-5-aminobenzoate, 4-dibenzoyl-methanisopropyl, 2-phenyl-benzimidazole-5- sulfonic acid, 2-hydroxy-4-methoxy-benzophenone-5-sulfonic acid, preferably in an amount in the range of about 0.5 to about 5 weight percent of the composition, insoluble pigments such as titanium dioxide, rutile dioxide titanium, octahedrite of titanium dioxide, sunscreens for example microfino pyrogenic titanium dioxide such as P 25®, Degussa, titanium dioxide micr ofino such as Sun Veil® Ikeda, microfine titanium dioxide with surface treated with silicones, or by amino acids, or by lecithin, or by metal stearates, microfine iron oxide, iron oxide with surface treated with silicones, or by amino acids, or by lecithin, or by metal stearates, zinc oxide, microfine zinc oxide such as UFZO® (Cosmo Trends Corporation), mica coated with titanium oxide, preferably in an amount in the range from about 0.5 to about 5 weight percent of the composition, preservatives such as methyl p-hydroxybenzoate, propyl p-hydroxybenzoate, phenoxyethanol, 2-bromo-2-nitropropane-1, 3-diol or mixtures thereof, preferably in an amount ranging from about 0.05 to about 3 weight percent of the composition, perfumes, preferably in an amount in the range from about 0.05 to about 0.6 weight percent of the composition, dyes, preferably in an amount in the range of about 3 × 10 ~ 3 weight percent of the composition, or mixtures thereof.

The invention is illustrated by means of the following Examples which are given as an example medium only. In the following Examples, the amount of each component is expressed as a percentage by weight of the total composition.

Example 1: night cream (water emulsion in silicone oil) Table 1 Composition of the oily phase Ingredient% _ Cyclomethicone "~ 5 Copolyol cyclomethicone / dimethicone 10 Dimethicone and dimethiconol 5 Ether of PPG-3 myristyl 1.5 Tocopherol acetate 0.5 Retinyl Palmitate (Note 1) 0.15 Beethic ester dimethicone 1 Table 2 Composition of the aqueous phase Ingredient% _ Tetrasodium EDTA 0.05 Sodium chloride 0.8 Glycerin 5 PEG-8 1.5 methyl p-hydroxybenzoate 0.25 propyl p-hydroxybenzoate 0.15 Phenoxiatanol 1 Magnesium ascorbyl phosphate (Note 2) (Nikkol VC-PMG) Aqueous preparation containing 0.5 protein hydrolyzed wheat (20%) polysorbate 20 (5%) and glycerin (5%) (Note 2) (Integrissyme) Aqueous solution 1% methylsilanol mannuronate (Note 2) (Algisium C) Red FD &C No. 40 1.5xl0"3 Perfume (Note 2) 0.15 Water Quantity Sufic.

Notes for Tables 1 and 2 (1) -It is preferred not to heat the retinyl palmitate with other compounds of the oily phase to prevent its oxidation. It is preferred to incorporate this in the phase at the beginning of the emulsification. (2) Heat sensitive compound.

The oily and aqueous phases, with the exception of the aforementioned heat-sensitive compounds, were heated separately at 50 + 1 ° C. They were then mixed with vigorous stirring by means of a microvortex-type stirrer (Rayneri®, France). Stirring was maintained at constant speed until the temperature of the emulsion dropped to 30 ° C. In this step, the homogenization rate was reduced and the heat sensitive ingredients were incorporated. The emulsification continued until the cream was homogenized completely.

Example 2: Day cream (multiple emulsion water in oil in water) Table 3 Composition of the primary emulsion Ingredient% _ Oily Phase Isohexadecane 2 Cetyl Octanoate 5 Cyclomethicone 3.5 Copolyol of cetildimethicone 4.2 Octyl methoxycinnamate 2 Butylmethoxydibenzoylmethane 0.5 Topoferol acetate 0.5 Retinyl Palmitate 0.15 Aqueous Phase Sodium Citrate 0.4 Magnesium sulfate 0.5 Tetrasodium EDTA 0.1 Xanthate rubber 0.1 Magnesium ascorbyl phosphate (Nikkol 1 VC-PGM) Pantenol 1 Propylene glycol 2.5 PEG-8 2 methyl p-hydroxybenzoate 0.2 propyl p-hydroxybenzoate 0.1 2-bromo-2-nitropropan-l, 3-diol 0.05 Perfume 0.15 Water 44 Table 4 Composition of the external aqueous phase Ingredient% _ Sodium hyaluronate 0. 03 PEG-8 2 methyl p-hydroxybenzoate 0. 2 propyl p-hydroxybenzoate 0. 1 2-bromo-2-nitropropan-l, 3-diol 0. 05 Polyglycerylmethacrylate / 5 Propylene Glycol / PVM / MA Red FD &C No. 40 1.5xl0"3 copolymer Ceteth-20 2.1 Sterol PEG-25 of soy 0.9 1% Aqueous solution of metiisilanol manuronate (Algisium C) Aqueous preparation containing 0.5 hydrolyzed wheat protein (20%) polysorbate 20 (5%) and glycerin (5%) (Integrissyme) Polymethyl methacrylate 0.8 Water Sufic.

The multiple emulsion was prepared using the two-step emulsion method as previously described in Tokgoz 1996. In this method the first water-in-oil emulsion was prepared and the emulsion was dispersed in the external aqueous phase containing hydrophilic emulsifiers, an aqueous emulsion agent. thickened, activating agents and other ingredients. In the first emulsification step to prepare the first water-in-oil emulsion, the phases (the oily and aqueous phases) were heated and mixed with in Example 1. However, in the second step, the first emulsion was incorporated dropwise to drop (incorporation time = 20 min) in the external phase at room temperature and agitation was performed at very low speed (homogenization time = 10 min).

Example 3: Day cream (oil in water emulsion containing a crystalline liquid phase) Table 5 Composition of the oily phase Ingredient%, Cyclomethicone 5 Dioctyl Succinate 3 Polyacrylamide (45%) / Isoparaffin 3 C13, C14 (25%) / Lauret-7 (8%) (Sepigel 305) Hydrogenated Lecithin 2 Topoferol Acetate 0.5 Retinyl Palmitate 0.15 Palmitic Acid 1 Alcohols C12, C16 1 Table 6 Composition of the aqueous phase Ingredient% Nilon-12 2 Gum of Esclerotiu 0.3 Tetrasodium EDTA 0.05 PEG-8 1.5 methyl p-hydroxybenzoate 0.25 propyl p-hydroxybenzoate 0.15 O-Cimen-5-ol 0.1 Magnesium ascorbyl phosphate 1 (Nikkol VC-PMG) An aqueous preparation containing 0.5 hydrolyzed wheat protein (20%) polysorbate 20 (5%) and glycerin (5%) (Integrissyme) Aqueous solution 1% methylsilanol manuronate (Algisium C) Red FD & C No. 40 1.5xl0"3 Perfume 0.40 Water Quantity Sufic.

The same preparation method was used for the preparation of Example 1.

Example 4: Lotion for the body (oil in water emulsion) Table 7 Composition of the oil phase Ingredient Isohexadecane 8 Mineral oil 5 Sorbitan stearate 2 Ceteth 20 2 Topoferol acetate 0. 5 Retinyl Palmitate 0. 15 Cyclomethicone 1 Hexadecyl alcohol 0. 5 Table 8 Compositions of the oily phase Ingredient Glycerin 5 Propylene glycol 5 methyl p-hydroxybenzoate 0.25 p-hydroxybenzoate -propyl 0.15 Sodium carbomer 0.35 Magnesium ascorbyl phosphate (Nikkol VC-PMG) An aqueous preparation containing 0.5 hydrolyzed wheat protein (20%) polysorbate 20 (5%) and glycerin (5%) (Integrissyme) Aqueous solution 1% methylsilanol mannuronate (Algisium C) Red FD &C No. 40 1.5xl0"3 Perfume 0.15 Water Quantity Sufic.

The same preparation method was used for the preparation of Example 1.

Example 5: day cream (oil-in-water emulsion without emulsifier) Table 9 Composition of the oily phase * Ingredient Isohexadecane 15 Miristyl myristate 3 Beeswax 1.5 Squalene 0.075 Titanium dioxide 1 Tocopherol acetate 0.5 Retinyl palmitate 0.15 Soybean sterol 0.5 Macadamia oil 0.2 Cyclomethicone 2 Hexadecyl alcohol 1.5 Table 10 Compositions of the aqueous phase Ingredient PoligliceriImetacrilato 4.8 Propylene glycol 0.12 PEG-8 3-p-hydroxybenzoate "methyl 0.25 p-hydroxybenzoate propyl 0.15 O-cimen-5-ol 0.1 2-Bromo-2-nitropropan-l, 3-diol 0.05 Tetrasodium EDTA 0.05 Sodium carbomer 0.35 Magnesium ascorbyl phosphate 1 (Nikkol VC-PMG) An aqueous preparation containing 0.5 hydrolyzed wheat protein (20%) polysorbate 20 (5%) and glycerin (5%. (Integrissyme) Aqueous solution 1% ethyl silanol manuronate (Algisium C) Red FD & C No. 40 1.5xl0"3 Perfume 0.15 Water Quantity Sufic.

The same preparation method was used for the preparation of Example 1.

Example 6 Table 11 Composition of the oily phase Ingredient Caprilic / Capric Triglyceride 3 Catearyl octonoate 4 Stearic Acid 1.5 Cetyl alcohol 1 Glyceryl stearate 2 Cyclomethicone 2 Tocopheryl acetate 0.5 Retinyl Palmitate 0.15 Sterol PEG-10 soy 1 Beeswax (Cera alba) 1.2 Cetyl Palmitate 3 Table 12 Compositions of the aqueous phase Ingredient% Tetrasodium EDTA 0.05 Gluceth-20 methyl 3 Glicereth-26 2 Acrylated polymers / 0.2 C10-30 alkyl acrylates (Pemuten TRI) Biosaccharide goma-1 (Fucogel 1000 pp) PEG-8 1.5 methyl p-hydroxybenzoate 0.3 p- propyl hydroxybenzoate 0.2 0-cimen-5-ol 0.1 Phenoxyethanol 0.90 Sodium hyaluronate 0.1 Sodium hydroxide 0.22 Magnesium ascorbyl phosphate 1 (Nikkol VC-PMG) Glycerin An aqueous preparation containing 0.5 hydrolyzed wheat protein (20%) polysorbate 20 (5%) and glycerin (5%) (Integrissyme) Aqueous solution 1% metilsilanol manuronate (Algisium C) An aqueous preparation containing glycerin (40%), PEG-18 (15%), Caprililglicol (4.5%), extract of Helianthus annuus (3%), ether of PPG-l-PEG-9 lauryl glycol (3%), butylene glycol (3%), Hederá helix extract (2%), phytic acid extract from rice bran (2%) and polyacrylate (0.5%) (Osmopur) Perfume Amount Sufic.

Water Quantity Sufic.

- The same preparation method was used for the preparation of Example 1.

In vitro glycosylation inhibition tests The methylated silanol derivatives (a Algisium C®), hydrolysed wheat proteins (Integrissyme®) and the compositions of the invention comprising these derivatives were initially subjected to a series of in vitro biochemical analyzes to determine their effectiveness. The test protocol used is known from the literature (Rosenberg et al 1979, Schinder and Kohn 1980) and is a simple test designed to induce non-enzymatic glycosylation of proteins under laboratory conditions.

The in vi tro analysis used consists of incubating serum albumin serum (BSA) and D-glucose and a sample of an active compound in a phosphate buffer (pH 7.4 at 37 ° C) for three weeks. This incubation gives a BSA with cross-links. Once glycosylated, BSA- is subjected to an acid hydrolysis reaction to release the reactive carbonyl groups of 5-hydroxymethylfuraldehyde (HMF). After precipitation and removal of the BSA from the medium, the addition of thiobarbituric acid (TBA) causes a coloration reaction to determine the amount of amine / hexose bonds that is proportional to the amount of glycosylated proteins. Anti-glycosylation compounds effectively reduce the amount of free HMF in the medium or, in other words, the amount of glycosylation.

The results of these tests are given in Figures 1 to 3. In these figures the percentage of glycosylation is shown as a function of the concentration of the active compound used. For Figure 1, only the active material is methylsilanol manure (Algisium C). For Figure 2, only the hydrolysed wheat protein extract (Integrissyme) is used. Figure 3 gives the results obtained using compositions comprising only methylsilanol manure (Algisium C concentration at 3 percent), or only hydrolyzed wheat protein extract (Integrissyme concentration 0.5 percent), or a mixture of methylsilanol manurate ( Algisium C concentration at 3 percent), and hydrolysed wheat protein extract (Integrissyme, concentration 0.5 percent).

As shown in Figures 1, 2 and 3, the combination of the two anti-glycosylation agents as described in the present application prevents glycosylation more effectively than if only one compound were used in large amounts.

In fact, the anti-glycosylation activity of hydrolyzed wheat protein extract (Integrissyme®) appears to be greater than that of methylsilanol manuronate (Algisium C®) when tested alone. With Algisium C®, only a significant decrease in glycosylation is obtained with concentrations greater than 7 percent. Algisium C® is ineffective when used at a 3 percent concentration. However, the combination of Algisium C® (3 percent) with Integrissyme® (0.5 percent) significantly reduces HMF in the medium.

Effect of the compositions of the invention of collagen synthesis in vi The effect of a composition of the present invention (comprising two anti-glycosylation agents with magnesium ascorbyl phosphate) on the stimulation of collagen synthesis and the limitation of the formation of irreversible bonds was evaluated in vitro in human fibroblast cells. between the collagen fibers.

The cells used were normal human fibroblasts (NHDF 784) used in the fourth step (R4) and were cultured at 37 ° C, under a 5% C02 atmosphere, in the following culture medium: MEM / M199, 3/1 (Gibco 31570021/2115130), sodium bicarbonate (gibco 25080060) 1.87mg / ml, L-glutamine (Gibco 25030024) 2 mmol / l, penicillin (polylabo 60703) 50 IU / ml, and fetal calving serum (v / v) Gibco 10106151) 10 percent.

- Six preparations were made in a sterile culture medium as follows: preparation 1: vitamin C (1 mg / ml) (Vit-C), preparation 2: magnesium ascorbyl phosphate (Nikkol VC-PMG 1 percent) preparation 3: D-glucose (1 percent) preparation 4: magnesium ascorbyl phosphate (Nikkol VC-PMG 1 percent) + metilsilanol manuronate (Algisium C 3 percent) (mixture 1), preparation 5: magnesium ascorbyl phosphate (Nikkol VC-PMG 1 percent) + hydrolyzed wheat protein (Integrissyme 0.5 percent) (mixture 2), and preparation 6: magnesium ascorbyl phosphate (Nikkol VC- PMG-1 percent) + metilsilanol manuronate (Algisium C 3 percent) + hydrolysed wheat protein (Integrissyme 0.5 percent) (mix 3), The fibroblasts were distributed in four plates of twenty wells (two plates for the synthesis of collagen, two plates for glycation) at a ratio of 9 x 104 cells / well and cultured for 24 h before the distribution of the products ( > 80 percent confluence).

The mixtures used in the study were in 1/40 dilutions in these evaluated solutions prepared in the sterile culture medium. These were non-cytotoxic doses, according to preliminary tests. Vitamin C was tested at the final concentration of 20 μg / ml (113 μmol / 1). This concentration is optimal for stimulating the synthesis of procollagen in vi tro (Freiberger et al 1980). The glucose was tested at the final concentration of 0.1, which is equivalent to twice the amount of "cold" glucose in the medium. Each of the experimental conditions was carried out in triplicate (three culture wells). The control wells received only 1.2 ml of the culture medium.

The incubation lasted 72 h, with renewal of the culture medium with intervals of 24 h. Metabolic localization was carried out during the last 24 h with 40 μCi per well (33.3 μCi / ml) of 1- [2, 3-3 H] -proline, 44 Ci / mmol (16.3 TBq / mol, Amersham, TRK628) or D- [5-3H] -glucose, 14.3 Ci / mmol (503 GBq / mmol, Amersham, TRK290).

At the end of the incubation, the plates containing the culture medium were subjected to a freeze / melt cycle. Sampling was taken of the middle of each of the wells (1.2ml), and each well was washed twice with 1ml of ice water. The culture medium and the washed solutions of each of the wells were added together. These were stored free of radioactivity and radioactivity incorporated in soluble cellular and extracellular proteins. The bottom of each well containing the insoluble material was washed again and the plates were stored on ice. Proteins from the soluble fraction were then precipitated in 0.3 by volume at 10 percent w / v trichloroacetic acid (TCA), and then washed twice with 3 percent TCA (remove free radioactivity). The proteins were purified by centrifugation in 42 individual columns (Micro-spin G-25, Pharmacia). This operation serves to remove any remaining trace of free radioactivity and to remove the TCA present in the samples (collagenase inhibitor).

Samples of soluble and insoluble proteins were then subjected to digestion by means of five units of ultrapure collagenase (Sigma, C0775) in a Tris-HCl 50 mmol / l, CaCl2 5mmol / l buffer (final concentrations), for 3 h at 37 ° C. The collagenase used contained 1390 units of collagenase / mg per 0.2 units / mg of neutral protease activity (caseinase). Aliquots were taken to count the radioactivity incorporated in the proteins and a final precipitation was performed with TCA to separate the material digested by the collagenase (collagenic origin) of the material insensitive to collagenase. The incorporated radioactivity was counted by polarizing the liquid before the accumulation of the soluble / insoluble protein fractions in a Rackbeta LKB 1211 counter.

The results of these tests show that the combination of the two anti-glycosylation agents (Algisium C® and Integrissyme®) with magnesium ascorbyl phosphate significantly increases the synthesis of the new collagen molecules, this is the incorporation of the radiellated proline. in the molecules of collagen synthesized "(Figure 4) .In addition, this fact is not accompanied by an increase of the glycosylated collagen in the medium, that is the incorporation of the radiolabelled glucose in the collagen matrix (Figure 5).

It appears in Figure 4 that vitamin C (alone), magnesium ascorbyl phosphate (alone), Mixture 2 and Mixture 3 stimulate collagen synthesis, that is, the amount of radiolabeled "proline" in the neosynthesized collagen was increased significantly. The best results were obtained with the combination of the two anti-glycosylation agents and the magnesium ascorbyl phosphate (mixture 3).

In contrast, mixture 1 had virtually no effect on the stimulation of collagen synthesis, and this caused an increase in the amount of irreversible bonds formed between the collagens (Figure 5). These results could be explained by a synergistic effect between the two anti-glycosylation agents preferably combined with magnesium ascorbyl phosphate.

In conclusion, collagen neosynthesis induced by mixture 3 was not accompanied by an increase in glycation rate. In other words, the glycation rate remains the same for different amounts of collagen. However, mixture 3 does not exhibit glycation strictly speaking, therefore an important effect can be inferred in collagen neosynthesis and a control (with limitation) of glycation.

Anti-pollution activity of the compositions of the present invention The anti-contamination activity of the compositions of the present invention was demonstrated in the following test.

Twenty volunteers with ages between 21 and 57 took part in the test. Three areas were selected on the forearm of each volunteer. "Example 6 of the product was applied in a first zone with a proportion of 2μl / cm2. A second zone of similar composition was applied as in Example 6 except that it did not contain the methylsilanol manuronate (Algisium C), the hydrolyzed wheat protein (Integrissyme), the magnesium ascorbyl phosphate (Nikkol VC-PMG) or the aqueous preparation It contains extracts of Helianthus annuus and Hederá helix and phytic acid (Osmopur) with a proportion of 2μl / cm2. The third zone was not treated. After twenty minutes a suspension of carbon was applied to each zone with a proportion of 2μl / cm2. Forty minutes later the areas were rinsed with water, dried with a tissue paper and allowed to dry in the air. Ten minutes later each area is scraped by the application of the adhesive tape to remove any remnant of carbon in the skin in each of the areas. The adhesive tapes were then examined with a video microscope to determine the amount of carbon remaining in each zone. The results were expressed as a percentage of protection P where P was calculated by means of the following formula P = [(ZNT - ZT) / ZNT] x 100 where ZNT is the amount of carbon remaining in the zone without treatment and ZT is the amount of carbon remaining in each zone. The average value of P calculated for the first zones of all the volunteers was 74% and the average value of P calculated for the second zones was 57%. These results were statistically significant (p <0.001 for student's t test). Increasing the P value increases the effectiveness of the composition by preventing the harmful consequences of exposure to air pollution.

References Lehninger A.L. Principies of biochemistry Worth Publications Inc 3rd Edition, 1984 Cerami A. Vlassara H. * and Brownlee M. Pour Science, July 72-79 (1987) Brownlee M., Vlassara H., Kooney A., Ulrich P. And Cerami A., Science, June, 1629-1631 ( 1986) Shin D. H., Hayase F. And Kato H., Agrie. Biol Chem., 5_2 1451-1458 (1988) Igaki N., Yamada H., Oimomi M. and Kasuga M., Clinic Chimica Acta, 199 113-116 (1991) Freiberger H., Grove D., Sivarajah A. and Pinnell S., J. Invest. Derrnatol. 7_5 425-430 (1980) Murad S., Sivarajah A. and Pinnell S., Biochem. BioPhys. Res. Commun. 101 868-875 (1981) Murad S., Tajima S., Sivarajah A. and Pinnell S., J. Invest. Derrnatol. , 8_1 158-162 (1983) Pinnell S., Murad S. and Darr D., Arch. Derrnatol. , 123 1684-1687 (1987) Tokgoz N.S., Doctoral Thesis in Pharmaceutical Science of the University of Paris-Sud, Paris XI, France, 1996 Rosenberg H., Modrak J.B., Hassing J.M., Al-Turk W.A. and Stohs S.J., Biochem Biophys Res Commun., 91_ 498-501 (1979) Schinder S.L. and Kohn R.R. J .. Clin. Invest. , \ 66 1179-1181 (1980) It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present invention.

Having described the invention as above, the content of the following is claimed as property.

Claims (22)

Claims

1. The dermatological and / or cosmetic composition for the treatment of symptoms of skin aging is characterized in that it comprises a combination of 0.01 to 0.2% by weight of the total composition of at least one methylated silanol derivative and 0.05 to 1% by weight of the total composition of at least one hydrolyzed vegetable protein derivative which is hydrolyzed barley protein, hydrolyzed wheat protein or hydrolyzed oat protein.

2. The composition of claim 1 is characterized in that the methylated silanol derivative is methylsilanol mannuronate.

3. The composition of claim 1 is characterized in that the hydrolyzed vegetable protein derivative is a hydrolyzed wheat protein extract.

4. The composition of any of claims 1 to 3 is characterized in that it also contains vitamin C and / or one or a plurality of its derivatives.

5. The composition of claim 4 is characterized in that the vitamin C derivative is magnesium ascorbyl phosphate.

6. The composition of any of claims 1 to 5 is characterized in that it also contains one or more oils extracted from vegetable sources and / or phytic acid.

7. The composition of claim 6 is characterized in that one or more of the oils are extracted from Helianthus annuus and / or Hederá helix and the phytic acid is extracted from the rice bran.

8. The composition of any one of claims 1 to 7 is characterized in that it further comprises an oligopeptide or a derivative thereof.

9. The composition of claim 8 is characterized in that the oligopeptide derivative is a polyoxylope oligopeptide wherein the oligopeptide is composed of glycine, histidine and lysine radicals or arginine, glycine, aspartic acid and serine radicals; the oligopeptide is a polypeptide composed of arginine and lysine radicals or the oligopeptide is a polypeptide of saccharomyces.

10. The composition of any one of claims 1 to 9 is characterized in that it also contains vitamin E and / or one or a plurality of its derivatives.

11. The composition of claim 10, characterized in that vitamin E or its derivative is DL-tocopherol or tocopheryl acetate.

12. The composition of any of claims 1 to 11 is characterized in that it also contains vitamin A and / or one or a plurality of its derivatives.

13. The composition of claim 12 is characterized in that the vitamin A or its derivative is retinol, retinyl acetate, or retinyl palmitate.

14. The composition of claim 4 or claim 5 is characterized in that vitamin C and / or its derivative is present in an amount from 0.25 to 30 weight percent of the composition.

15. A composition as claimed in claim 6 or claim 7, is characterized in that each or more of the vegetable oils and / or phytic acid are present in an amount from about 0.005 to 0.05% of the composition.

16. A composition as claimed in claim 7, characterized in that the oil extracted from Helianthus annuus is present in an amount from about 0.01 to 0.04% of the composition, the oil extracted from Hederá helix is present in an amount from about 0.01 to 0.04. % of the composition and phytic acid (if present) is present in an amount from about 0.01 to 0.04% of the composition.

17. The composition of claim 10 or claim 11 is characterized in that the vitamin E and / or its derivatives are present in an amount from about 0.05 to 2 weight percent of the composition.

18. The composition of claim 12 or claim 13 is characterized in that the vitamin A and / or its derivatives are present in an amount from about 0.02 to 1 weight percent of the composition.

19. The composition of any of claims 1 to 18 is characterized in that the composition is in the form of a water / oil emulsion, a water / oil silicone emulsion, an oil / water emulsion, a water / oil / water multiple emulsion or a pseudo ulsion

20. The composition of claim 19 is characterized in that the composition is in the form of a water / oil silicone emulsion or in the form of multiple water / oil / water emulsion.

21. The use of a composition of any of claims 1 to 20 as a medicinal product.

22. The use of a combination of 0.01% to 0.2% by weight of the total composition of at least one methylated silanol derivative and 0.05 to 1% by weight of the total composition of at least one hydrolyzed vegetable protein derivative which is barley protein hydrolyzed, hydrolyzed wheat protein or hydrolyzed oat protein for the preparation of a medicinal product as claimed in any of the claims 20 for the treatment of the symptoms of skin aging or for the treatment of the consequences of exposure to air pollution.