WO2008080443A2

WO2008080443A2 - Cosmetic composition for the treatment and/or prevention of skin stretch marks

Info

Publication number: WO2008080443A2
Application number: PCT/EP2007/009253
Authority: WO
Inventors: Daniela Montanari; Manuela Guglielmo
Original assignee: Labo Cosprophar AG
Current assignee: Labo Cosprophar AG
Priority date: 2007-01-04
Filing date: 2007-10-24
Publication date: 2008-07-10
Anticipated expiration: 2009-07-04
Also published as: WO2008080443A3; EP2101879A2; CH696659A5; CH696659A9

Abstract

The present invention relates to a cosmetic composition for the treatment and/or prevention of skin stretch marks based on the synergic association of a base formulation containing matrikine (s), rutin and Phaseolus extract, with one or more active principles of a natural origin selected from real aloe extract, vitamin E, sericin, Delesseria sanguinea extract, Saccharomices lysate, Chlorella alga extract, lipopeptide comprising the amino-acid sequence Lys-Thr-Thr-Lys-Ser.

Description

COSMETIC COMPOSITION FOR THE TREATMENT AND/OR PREVENTION OF SKIN STRETCH MARKS

The present invention relates to a cosmetic composi- tion for the treatment and/or prevention of skin stretch marks .

The present invention derives from the cosmetic field and in particular the section of formulations with an anti- stretch mark action. Stretch-marks, also known as "striae distensae" or "striae atrophicae" , are a type of atrophy of the skin characterized by linear depressions, well-defined, of a generally asymptomatic nature particularly widespread in female individuals. The striae can appear in any part of the body, except the face and endpoints. They generally arise bilaterally. They are mainly formed in areas subject to rapid tension over a short period of time, following lacerations of the connective tissue of the derma. The area most frequently struck by striae is the abdominal region where the arrangement varies as the direction of maximum skin tension is not constant and can undergo changes for various reasons (pre- and post-pregnancy) ; on the hips they are often transversal; on the thighs they are more or less oblique with respect to the internal surface; in the lumbosacral region they are horizontal. They also frequently appear on the breast.

They appear as linear bands, separated by areas of healthy skin, with distinct edges. They are various cen- timeters long and from 3 to 10 mm wide. From a histological point of view the striae correspond to a thinning of the epidermis with atrophy of the collagen strips of the derma, associated with a reduction in the elastic fibres which, at the edges of the stretch marks, appear re- tracted and thinned. This area of the atrophy is not vascularized.

Their appearance is generally asymptomatic, even if at times it can be accompanied by slight itching. The colour depends on their development phase: at the begin- ning, when the inflammatory component is prevalent, the colour varies from pink, to pinkish-purple, or reddish- blue, whereas subsequently, in the cicatricial phase, the striae are thinner, curved and become whitish.

Stretch marks strike females with a frequency which is twice that of males; they can appear at any age but mostly during puberty.

In pregnancy, approximately 55-90% of women are affected.

The main physiological states which can cause the appearance of stretch marks are the following: puberty, pregnancy, more or less intensive practicing of sports for developing the muscles, rapid weight loss and/or increase. Mechanical distension induced by a rapid and sudden trauma, either small or repeated, can also cause the formation of striae.

Little is still known of the physiopathological mechanism for the formation of striae. It appears, however, that the triggering causes can be mainly attributed to i) a biochemical-hormonal factor and ii) a mechanical stretching factor, i.e. an exaggerated tensioning of the skin due to a sudden variation both in excess and in defect of the adipose panniculus or of some parts of the body such as the abdomen, glutei and thighs.

The hormonal factor causes a loss in elasticity and a decrease in the connective fibres ; hormones (essentially corticosteroids) do in fact interfere with the activity of the fibroblasts, the quality and quantity of collagen and elastic fibres, the characteristics of the fundamental substance and functionality of the microcir- cle. The mechanical stretch factor acts on this area causing the breakage of the collagen fibres.

Repeated local microtraumas or progressive elongation of the skin also cause a stretching of the dermal capillaries, with a consequent reduced blood flow to the cutaneous structures and a consequent district ischemia; a reduction in the oxygen supply and nutritive substances causes metabolic suffering increasing the atrophy.

The formation of stretch marks essentially takes place in three different moments: - a pre-clinical (or inflammatory) phase characterized by a blockage of the fibroblast function and a physico- chemical modification of the fundamental substance (decrease in the mucopolysaccharides and reduced activity of the glycolytic enzymes) , with a consequent alteration in the collagen and elastic fibres; a regenerative phase, clinically corresponding to striae rubrae, characterized by the restarting of the enzymatic activity, with a reactivation of the fibroblasts, increase in the mast cells, restarting of the production of mucopolysaccharides;

- a healing phase, clinically corresponding to striae al- bai, consisting of the normalization of the enzymatic activity of the fibroblasts, regeneration firstly of the collagen fibres and then of the elastic fibres with res- toration of the damaged connective tissue. The histological aspect of the striae differs according to their development phase. In the preclinical phases and very initial lesions, the epidermis does not appear modified. The biochemical alterations of the fun- damental substance and fibrous component, which create the conditions for the formation of stretch marks, are revealed on the part of the procollagen type I and III and fibronectin. In striae rubrae, the collagen fibres are not yet compact and are separate from the derma, they are arranged parallel to the skin surface and their structure appears almost normal. The elastic fibres are more elongated. A discreet perivascular lymphocytary infiltration with mononucleate cells is also revealed together with an increase in the Langherans cells in the derma. The mast cells appear degranulated and the release of tripsin and chemotripsin causes collagenolysis and elastolysis particularly at the centre of the forming stretch mark. The epidermis subsequently becomes thin and flattened and with a loss in the papillary design. The derma also becomes thin and is also considerably altered in the collagen and elastic component. In the intermediate and deep derma there is a marked elastolysis relating to the fact that the macrophages release elastase . The collagen consists, in the upper part of the derma, of thin, elongated strips parallel to the surface of the skin, whereas below, the strips are compacted, thicker and irregularly arranged. The fibroblasts are in quiescence phase. This compacting is linked to a reduction in the fundamental amorphous substance of the connective, due to the low production of acid mucopolysaccharides. The elastic tissue can appear differently depending on whether the biopsy has been effected in a precocious or late phase. In general, the elastic fibres are elongated and arranged parallel to the epidermis in the surface part of the derma. In the underlying derma they are more rarefied and fragmented, smaller than usual but more numerous than in integral skin.

Today stretch marks can no longer be considered as being indelible lesions even if the possibility of a re- gression often remains limited and in any case conditioned by the period of the formation of striae and stage of their cicatrisation process .

Numerous cosmetic formulations with an anti-stretch mark action are currently available on the market. Some of these formulations with an anti-stretch mark action however contain active principles of a synthetic origin whose prolonged use can cause the formation of local and non-local side-effects.

Other anti-stretch mark formulations of the known type have a cosmetic efficacy which is not always satis- factory .

In the present state, the necessity is therefore felt for availing of new formulations for cosmetic use having a satisfactory capacity for the treatment and pre- vention of the formation of stretch marks.

One of the objectives of the present invention therefore consists in providing a cosmetic composition for local application capable of treating both stretch marks already present diminishing their visibility and also preventing their formation.

In particular, the Applicant has found that by associating a base formulation containing the active principles matrikine (s) , rutin, Phaseolus lunatus extract with at least another selected active principle having an ac- tivity on one of the components at the origin of stretch marks, a synergic attenuation effect is obtained of the visibility of stretch marks and limitation of their formation.

According to a first aspect of the present inven- tion, a cosmetic composition is therefore provided for the treatment/prevention of stretch marks comprising the association of matrikine (s) , rutin, Phaseolus extract, preferably of the lunatus kind with one or more active principles selected from real aloe extract, vitamin E, sericin, Delesseria sanguinea extract, Saccharomices lys- ate, Chlorella alga extract, lipopeptide comprising Lys- Thr-Thr-Lys-Ser .

In accordance with this aspect, the composition of the invention envisages a combination of base active principles (base formulation) , each of which has its specific activity, which works in synergy with one or more further active principles which, by acting on different or complementary means which lead to the formation of stretch marks, allow an intervention to be effected under various profiles with a complementary and synergic procedure .

The composition of the invention, by stimulating the cellular reproduction of the connective tissue and relative production of collagen fibre suitable for restoring the damaged tissue, is typically capable of mitigating the redness which accompanies the appearance of stretch marks, of elasticizing, hydrating, calming and smoothing the cutaneous area treated.

It has also been observed that the composition of the invention not only has the cosmetic properties indicated above but also the capacity of improving the microcirculation of the skin.

The composition of the invention can be typically presented in any formulation suitable for skin applica- tion such as creams, emulsions, gels, milks, oils, etc. The use of the composition of the invention envisages the local application of a cosmetically effective quantity on the area subject to stretch marks and on areas of the body which are most typically subject to their formation.

In the base formulation of the composition of the invention, the following products are conveniently present A) one or more matrikines, B) rutin and C) a Phaseolus extract of the lunatus kind. A) Matrikines are peptide fragments with a sequence of less than or equal to 20 amino acids. They are formed by the proteolysis of the extracellular matrix and are capable of regulating the cellular activity.

According to an embodiment, matrikines containing peptide fragments with 3 or 4 amino acids (tri- or tetrapeptide) are used in the composition of the invention.

Two matrikines are particularly suitable, Glycyl- Histidyl-Lysine peptides and Glycyl-Glutaminyl-Prolyl- Arginine peptides (both conveniently having a molecular weight of 200 ppm) , involved in the synthesis of the dermal matrix, in particular collagen, the main protein of the connective tissue, and of fibronectin, a molecule responsible for the connection between the extracellular matrix and the cellular surface. These two matrikines also promote the cellular proliferation of keratinocytes and fibroblasts and are consequently effective in the reconstruction of the extracellular dermal matrix. The former, glycine-histidine-Lysine tripeptide, derives from the α2 chain of collagen I. The biological activity of said tripeptide has been described in numerous in vitro studies which have shown an increase in the synthesis of collagen (+350%) and glycosaminoglycans (+46%), and also a reparative and protective action with respect to collagen.

The second matrikine, glycine-glutamine-prolme- arginine tetrapeptide is a natural fragment of the immunoglobulin IgG which has various biological activities especially immunological. The biological activity of this tetrapeptide has been described in numerous in vitro studies which have revealed a decrease in the secretion of interleukin 6 (IL6) on the part of keratinocytes, responsible for the inflammatory process. A test in vivo, on the other hand, has shown the toning (+19%) , elasti- cizing (+17%) and hydrating (+24%) activity of the tetrapeptide .

B) Rutin, the second component of the base formulation, has antioxidant properties, it stabilizes the mast cells and inhibits leukocyte elastase. The vegetable extract inhibits proteolytic enzymes such as tripsin and chemo- tripsin, released during the inflammatory phase which leads to the formation of stretch marks.

C) The third component of the base formulation is an extract, processed with traditional techniques, of the bean plant in particular of the species Phaseolus Luna- tus .

A test was effected in vitro in which tripsin, chemotripsin and elastase were incubated with the base formulation containing the three components described above at different concentrations.

The inhibition kinetics were monitored for several minutes. The combination of the two matrikines with Rutin and vegetable extract inhibits the proteolytic enzymes according to a dose-dependent trend.

At a concentration of 4% of the above combination, the inhibition of the activity of the enzymes are as follows: tripsin -58%, chemotripsin -15% and elastase -90%. A second test in vitro was effected incubating human fibroblasts with 2% of the combination of the three components described above. After incubation collagen I and the fibronectins produced by the cells are quantified by immunodosage and visualized with Immunofluorescence. The combination stimulates the neosynthesis of the macromole- cules of the matrix: collagen I +102% and fibronectin +91% with respect to the control.

A test in vivo was effected: 13 volunteers with problems of stretch marks due to weight increase applied a cream, twice a day, containing the base formulation A) two matrikines: glycine-histidine- lysine tripeptide and glycine-glutamine-proline-arginine tetrapeptide, B) Rutin and C) Phaseolus vegetable extract: the characterization of the stretch marks was effected by echography and with the evaluation of a dermatologist. The ultrasounds al- lowed the average increase in the thickness of the stretch-marked skin to be verified (+10.8%) and the reduction in the depression of the stretch marks (-72.5%) after the treatment. The dermatologist evaluated the variations in the colouring, protuberance and extent of the stretch marks assigning a mark from 0 to 10. After the treatment the average variations observed were: colour -21.7%, protuberance -21.9% and extent of the stretch marks -26.7%.

Real Aloe, an active principle used in an embodiment of the composition of the invention, has dereddening, soothing and hydrating properties . It also has very interesting cicatrizing properties for the treatment of stretch marks; application on artificial skin demonstrated that the glycoproteins contained therein are ca- pable of stimulating the formation of the epidermal tis- sue, promoting the formation of new cells. In the tissue in contact with the active principle, an increase is observed in the epidermal growth factor, fibronectin and keratin and cell receptors to which these substances are physiologically linked; there is an accelerated migration of keratinocytes and an increase in the expression of factors relating to cell proliferation.

The anti- inflammatory and antioxidant properties of aloe can be mainly attributed to the presence of isoen- zymes of superoxide dismutase, and also immunostimulting, thanks to the presence of acemmanan.

The rich polysaccharide composition of the real Aloe extracts can give cosmetic products hydrating properties. A study has allowed the effect of cosmetic formulation at different concentrations of lyophilized extract of real Aloe to be evaluated, through skin bioengineering techniques. The results obtained indicate that lyophilized real Aloe extract is a natural ingredient capable of improving skin hydration, probably through a mechanism of the moistening type.

Vitamin E, an active principle used in an embodiment of the composition of the invention, protects the lipids and lipoproteins of the cell membranes and consequently has a beneficial effect on the water-binding capacity of the skin. It improves the barrier functions of the epi- dermis by reducing the Trans Epidermal Water Loss (TEWL) . It is therefore considered a natural moisturizing substance for the skin and is ideal for dry skin.

It has an anti-inflammatory action. In particular, the hydrophilic derivative of γ-tocopherol significantly inhibits the production of prostaglandins E2 (PGE2), secondary messengers of the inflammation signal and the production of cyclo-oxygenase 2 (COX-2) , a key enzyme required for the synthesis of PGE2. Sericin, used in an embodiment of the composition of the invention, represents the second silk protein, after fibroin. It is a globular protein whose amino acid composition is the following: alanine, glycine, isoleucine, leucine, proline, valine, tyrosine, asparagine, gluta- mine, arginine, histidine, lysine, serine, threonine.

Applied on the skin in aqueous solution, it initially forms a viscous film which, after drying, gives a smooth, velvety, healing sensation of the skin. The fil- mogen capacity increases with an increase in the molecu- lar weight. Due to the conformation and presence of numerous hydrophilic and oligosaccharide chain areas, Sericin is capable of improving the skin hydration structure. The dynamic measurement of the Trans Epidermal Water Loss, relating to humidity exchanges between the skin and outside environment, has given satisfactory results: Sericin has a marked hydrating effect, with a prolonged action of increasing the epidermal barrier. The hydrating action is mainly linked to the filmogen effect, without occlusion. Sericin has also proved to have a marked smoothing effect on skin irregularity. Imprints were effected of skin prominences both before and 21 days after treatment with Sericin cream: the results showed a clear mitigation of skin irregularity.

It is known that Sericin increases the adhesion and growth of fibroblasts under culture.

The effect of Sericin on cultures of human fibroblasts was recently examined to test its application on lesion of the skin. It was verified that when human fibroblasts were cultivated with 2.5 or 25 micr/cm² of Sericin, the cell count after 72 hours of cultivation was equal to 150% more with respect to the negative control. The adhesion and consequent proliferation of fibroblasts can have an important role in the cicatrisation of wounds and therefore be validly applied in the field of the treatment of stretch marks.

Delesseria sanguinea, used as extract in an embodiment of the composition of the invention, is a red alga of the Rodoficee group.

It grows in the North Sea and in the north Atlantic. Delesseria sanguinea extract, used as active princi- pie in an embodiment of the invention, is typically obtained by means of a procedure which comprises the following phases :

- collection of the algae - selection of the algae

- deep-freezing at -20⁰C

- drying

- osmotic shock with the addition of water

- percolation of the solvent - recirculation of the solvent for about 1.5 hours

- concentration and formation of the end-product.

Delesseria extract has positive effects on the subcutaneous microcirculation. The effect of Delesseria extract was evaluated using a carbopol gel at 5% of extract and application on the forearm of 15 volunteers twice a day for 28 days. The test was carried out against placebo. The surface microcirculation was measured by thermal conductivity measurements using a thermal probe applied directly to the skin. It is known that the thermal conductivity is directly proportional to the skin microcirculation. 28 days after application twice a day, the placebo had not modified the microcirculation (+0.11+/- 0.12 mW/cm°C) , whereas the gel containing 5% of Delesseria extract significantly increased the skin microcircu- lation (+0.48 +/-0.21 mW/cm°C) . This effect was observed in 80% of the volunteers. Saccharomices lysate, used in an embodiment of the composition of the invention, typically contains low molecular weight active substances which derive from yeast cultures, produced under aerobic conditions, of the species "Saccharomices cerevisiae" . This lysate reactivates cell tissue regeneration. The following amino acids are typically included in its composition: aspartic acid, threonine, serine, glutamic acid, proline, glycine, alanine, valine, methionine, isoleucine, leucine, tyrosine, phenylalanine, lysine, histidine, arginine, cystine.

For the production of lysate, the following production phases can be followed: 1. preculture

2. aerobic fermentation

3. cell collection

4. selective cell lysis

5. subcell fractionation 6. separation of the insoluble fragments

7. formation of the raw fraction

8. selective precipitation

9. purification

10. concentration of the active fraction 11. filtration through a membrane 12. formation of the purified active fraction

13. sterilizing filtration

An evaluation study was effected on the stimulation of the cell turnover using the dansyl chloride technique. A vaseline oil solution at 5% of dansyl chloride was applied on the forearm of 12 volunteers, in 3 different areas, in a quantity of about 4 mg/cm². A non-occlusive bandage was placed above each area. The bandages were removed after 24 hours and the treated areas were examined using a specific lamp for monitoring the fluorescence intensity. The 3 sites of each forearm were treated with the product, twice a day. On days 1, 7, 10 and all the subsequent days, the subjects were examined and the variation in the fluorescence intensity due to the dansyl chloride, was evaluated. The endpoints (elimination of all the colour) were determined and the percentage increase in the cell renewal rate was then calculated.

The "Saccharomices cerevisiae" lysate produced an increase percentage of the cell turnover of 17% with 3% of active principle and 25% with 5% of active principle.

Chlorella alga extract, used in an embodiment of the composition of the invention, is obtained from cultivations of a unicellular green microalga, Chlorella alga.

The alga is cultivated in polyethylene tubes which allow a preservation of monospecific cultures. The main processing phases for obtaining Chlorella extract comprise:

1. solubilization of Chlorella in water

2. separation of the soluble and insoluble phases by fil- tration

3. sterilizing filtration of the soluble part

Chlorella alga extract has a high content of trace elements (iron, copper, zinc, manganese), minerals (sodium, potassium, calcium) and amino acids, 60% of which is represented by essential amino acids (isoleucine, methionine, phenylalanine, threonine, tryptophan, valine, arginine, histidine) .

Among amino acids, arginine, present in a high quantity, is a precursor of ornithine in turn a precursor of spermine and spermidine, the latter non-peptide growth factors which have the capacity of stimulating cell division and activating protein synthesis.

Finally, the high content of hydrosoluble vitamins (Bl, B2, B12, PP) effectively intervenes on the protein synthesis. By acting as mediators, in fact, they promote the release of energy in the form of ATP, both directly by means of the Krebs cycle (Vitamin Bl) and by means of the respiratory chain (vitamin B2 , PP) . This energy is rapidly reused for reintegrating the protein synthesis . From in vitro tests carried out on Chlorella alga extract it has been demonstrated that it is capable of stimulating cell proliferation. By using cell cultures under sub-optimal conditions, i.e. which simulate a deficiency state of growth factors and nutritive elements, a strong multiplication activity of the cells treated, with respect to the non- treated cells, is observed.

A further component, present in an embodiment of the composition of the invention consists of a synthesis Ii- popeptide, having the sequence Lys-Thr-Thr-Lys-Ser (typi- cally 100 ppm) . In vitro studies show that this lipopep- tide induces the cells to synthesize collagen and glyco- saminoglycanes .

Said lipopeptide carries a molecule of palmitic acid connected to the sequence of amino acids described above, to increase its affinity towards the skin and its bioavailability.

In vitro tests were effected on said lipopeptide, as described hereunder. In vitro tests The test adopted showed the capacity of the Peptide of stimulating the neo-synthesis of collagen type IV, particularly important for the dermal-epidermal joining of the skin (the latter associated with skin elasticity) ; after cultivating human fibroblasts with and without the Peptide at different concentrations, the proteins neo- synthesized in the culture medium were collected. At the concentrations tested, the Peptide caused an increase in the production of collagen IV equal to 50% with respect to the control (culture of fibroblasts without Peptide) . The production of soluble collagen IV increased by a factor ranging from 2 to 4 , on the basis of the concentration of Peptide.

Another important category of molecules whose production is stimulated by the Peptide is that represented by glycosaminoglycanes .

Human fibroblasts were incubated for 24 hours with and without the Peptide in the presence of a radio-marked precursor, 3H-glucosamine, which is incorporated in the freshly synthesized glycosaminoglycanes . These GAGs are secreted from the fibroblasts and deposited in the culture medium. The Peptide significantly increased the synthesis of GAG: +267% with respect to the control medium at a concentration of 2%.

A particularly preferred embodiment of the invention envisages the association of the base formulation containing matrikines, rutin and Phaseolus extract, preferably of the lunatus kind with real aloe extract, vitamin E, Sericin, Delesseria sanguinea extract, Saccharomices lysate, Chlorella alga extract, lipopeptide of the amino acid sequence lysine-threonine-threonine-lysine-serine (Lys -Thr-Thr-Lys -Ser) .

According to another aspect of the present invention, a method is provided for the treatment and/or prevention of stretch marks comprising application on the body area to be treated of a cosmetically effective quantity of a composition comprising matrikines (s) , rutin, lunatus Phaseolus extract, associated with one or more active principles selected from real aloe extract, vitamin E, Sericin, Delesseria sanguinea extract, Saccharomi- ces lysate, Chlorella alga extract, lipopeptide comprising Lys-Thr-Thr-Lys-Ser.

It has been observed that the use of a cosmetic composition of this type produces the following effects :

1. reactivation of the fibroblast activity to re-start the production of collagen, fibronectin and elastin and inhibition of the proteolytic enzymes responsible for the degradation of the dermal matrix, thanks to the activity of the matrikines together with rutin and vegetable extract. The new fibres reconstruct the damaged connective tissue with a reduction in the inflammation.

2. stimulation of the proliferation of the fibroblasts and production of the fundamental amorphous substance of the derma for restoring the thickness of the derma, which has thinned during the development of the stretch marks thanks to the presence of Chlorella alga extract and Palmitoyl-Lys-Thr-Thr-Lys-Ser Peptide.

3. re-establishment of the local subcutaneous microcircu- lation and consequent supply of nutritive substances and oxygen with a consequent improvement in the trophism of the area subject to stretch marks, thanks to the Delesseria sanguinea extract .

4. lenitive and dereddening action, important especially during the inflammation phase of the stretch mark thanks to the presence of Aloe. Aloe is also important as it stimulates the formation of the epidermal tissue.

5. hydrating and softening action of vitamin E, it helps to restore the elasticity of the skin which in this way is more resistant to stretching and mechanical stress .

6. smoothing action on skin irregularity thanks to the silk proteins; the skin is soft and smooth. It also contribute to the hydration of the skin.

7. releasing of the surface skin layer consisting of dead cells, thanks to "Saccaromices cerevisiae" lysate which smoothes the skin making it smoother and more compact, and at the same time it improves the penetra- tion capacity of the cosmetic product applied. For the preparation of the cosmetic compositions of the invention, the equipment normally at the disposal of the technologies according to procedures known to experts in the field, is used. The active principles are added and dispersed inside a physiologically acceptable container following procedures known to experts in the field, conveniently adding one or more additive substances such as stabilizers, emulsifying agents, excipients, preservatives, perfumes and suspending agents.

The cosmetic compositions of the invention are conveniently suitable for local application and can comprise additives and excipients commonly used in cosmetic preparations, such as preservatives, bactericide agents, sta- bilizers, emulsifying agents, buffers, dyes and other excipients .

The following examples are provided for purely illustrative purposes of the present invention and should not be considered as limiting the protection scope, as specified in the enclosed claims. EXAMPLE 1

Formulation of cosmetic compositions according to the invention: glyceryl stearate 1-5% cetylstearyl (12) OE 1-5% polysorbate 80 0.5-1% cetyl alcohol 1-3% octyldodecanol 1-3% cetylstearylisononanoate 1-3%

C₈-Io triglyceride 10-20% diemthylpolysilyloxane 0.01-0.1% wheat germ oil 0.8% tocopheryl acetate 0.1% real aloe 0.010% matrikines : Glycyl-Histidyl-Lysine and Glycyl-Glutaminyl-Prolyl-Arginine 0.001% rutin 0.001%

Phaseolus lunatus extract 0.02% sericin 0.1% delesseria sanguinea extract 0.08%

Chlorella alga extract 0.08%

Peptide (Lys-Thr-Thr-Lys-Ser) 0.002% saccharoraices lysate 0.04% antioxidants and preservatives as sufficient water complement to 100

EXAMPLE 2

Formulation of cosmetic emulsions according to the inven tion: glyceryl stearate 2-5% cetylstearyl (12) OE 3-5% polysorbate 80 0.5-1% cetyl alcohol 2-3% octyldodecanol 3-4% butyl alcohol (26) OP (26) OE 0.8% cetylstearylisononanoate 2-3%

C_8-I₀ triglyceride 15-20% diemthylpolysilyloxane 0.08% wheat germ oil 0.8% tocopheryl acetate 0.2% real aloe 0.06% matrikines : Glycyl-Histidyl-Lysine and Glycyl-Glutaminyl-Prolyl-Arginine 0.001% rutin 0.01%

Phaseolus lunatus extract 0.02% sericin 0.2% delesseria sanguinea extract 0.25%

Chlorella alga extract 0.3%

Peptide (Lys-Thr-Thr-Lys-Ser) 0.001% saccharomices lysate 0.35% citric acid 0.2% antioxidants and preservatives as sufficient water complement to 100 perfume

EXAMPLE 3 glyceryl stearate 4% cetylstearyl (12) OE 4% polysorbate 80 0.5% cetyl alcohol 3.5% octyldodecanol 2.8% butyl alcohol (26) OP (26) OE 3% cetylstearylisononanoate 2.5%

C₈-Io triglyceride 14% diemthylpolysilyloxane 0.08% wheat germ oil 1.0% tocopheryl acetate 0.35% real aloe 0.1% matrikines : Glycyl-Histidyl-Lysine and Glycyl-Glutaminy1-Prolyl-Arginine 0.002% rutin 0.01%

Phaseolus lunatus extract 0.03% sericin 0.5% delesseria sanguinea extract 0.5%

Chlorella alga extract 0.2%

Peptide (Lys-Thr-Thr-Lys-Ser) 0.001% saccharomices lysate 0.65% citric acid 0.2% antioxidants and preservatives as sufficient water complement to 100 perfume

EXAMPLE 4 Effectiveness test

A study in vivo was effected on the cosmetic preparation of Example 3, under medical-dermatological control, for evaluating the cosmetic effectiveness in the treatment of stretch marks .

20 women aged between 18 and 45 years with recently formed stretch marks (striae rubrae) , were included in the study. The volunteers used two different types of emulsion, one as local treatment on the stretch mark to be used with a specific precision applier and one as integration product.

The procedure of use of the products was as follows: apply in the evening, for 30 consecutive days, approximately 2 ml of product for local treatment directly on the striae to be treated, with the specific precision applier. Let the product act for 10 minutes, then massage the stretch mark until complete absorption. The following morning, apply the integration product on the stretch marks, delicately massaging until complete absorption. The cosmetic effectiveness was evaluated with a subjective evaluation on the part of the volunteers participating in the experiment, who, after 4 weeks of treatment, expressed their opinion according to the following statements : - the product reduces the stretch marks - the product makes the stretch marks less evident

- the product lightens the colour of the stretch marks

- the product makes the skin more elastic

- the product makes the skin more hydrated - the product makes the skin smoother

After the first 28 days of treatment, the results were the following:

- 45% of the volunteers declared that the products being tested reduce the stretch marks; - 60% of the volunteers declared that the products being tested makes the stretch marks less evident;

- 60% of the volunteers declared that the products being tested lighten the colour of the stretch marks ;

- 60% of the volunteers declared that the products be- ing tested makes the skin more elastic;

- 100% of the volunteers declared that the products being tested makes the skin more hydrated;

- 100% of the volunteers declared that the products being tested makes the skin smoother. After 8 weeks of treatment the opinions of the volunteers were the following:

- 75% of the volunteers declared that the products being tested reduce the stretch marks;

75% of the volunteers declared that the products be- ing tested makes the stretch marks less evident; - 75% of the volunteers declared that the products being tested lighten the colour of the stretch marks;

- 75% of the volunteers declared that the products being tested makes the skin more elastic; - 100% of the volunteers declared that the products being tested makes the skin more hydrated;

- 100% of the volunteers declared that the products being tested makes the skin smoother.

A second test was also effected, i.e. a self- evaluation test on a sample of 91 women with recently formed stretch marks who applied the two products with the same procedure described above.

At the end of the test, after 4 weeks, the sample of women was subjected to a brief self-evaluation test. To the question "With the application of the preparation, did you notice a reduction in the stretch marks of the skin?" ²A of the women (74.7%) who took part in the research declared that they had noticed a reduction in the stretch marks after the application of the two prod- ucts being tested.

To the question "Do you think that with the application of the preparation, the skin is more elastic and smoother?" almost all of the sample (98.9%) replied that the application of the product is useful for obtaining a more elastic and smoother skin. To the question "Do you find that the application procedure of the preparation above the line of the stretch mark with a syringe and cannula is easy, complex but functional, complex or difficult?" almost 42% of the sample considered the application procedure easy, whereas 31.9% considered it complex but functional. BIBLIOGRAPHICAL REFERENCES

- "Cryptic sites and matrikines : cellular effects of fi- bronectin and laminin peptides", Labat-Robert J., J.Soc.Biol. 2003; 197(1): 45-51.

- "An introduction to matrikines : extracellular matrix- derived peptides which regulate cell activity. Implication in tumor invasion", Maquart FX, Pasco S, Ramont L, Hornebeck W, Monboisse JC, Crit. Rev. Oncol. Hematol . 2004 Mar., 49(3): 199-202.

- "Regulation of cell activity by the extracellular matrix: the concept of matrikines", Maquart FX, Simeon A, Pasco S, Morboisse JC, J.Soc.Biol. 1999; 193(4-5): 423-8.

- "Matrix metalloproteinases and matrikines in angiogene- sis", Bellon G, Martiny L, Robinet A,

Crit. Rev. Oncol. Hematol. 2004 Mar; 49(3): 203-20.

- "Elastin as a matricine" , Duca L, Floquet N, Alix AJ, Haye B, Crit .Rev. Oncol .Hematol 2004 Mar,- 49(3): 235-44.

- "Matrikines in the regulation of extracellular matrix degradation", Maquart FX, Bellon G, Pasco S, Monboisse JC, Biochimie 2005 Mar-Apr; 87(3-4) : 353-60

Claims

1. A cosmetic composition for the treatment and/or prevention of stretch marks of the skin comprising the asso- ciation of a base formulation comprising matrikine (s) , rutin, Phaseolus extract with one or more active principles selected from real aloe extract, vitamin E, sericin, Delesseria sanguinea extract, Saccharomices lysate, Chlorella alga extract, peptide comprising the amino-acid sequence Lys-Thr-Thr-Lys-Ser and a cosmetically acceptable carrier.

2. The cosmetic composition according to claim 1, wherein said matrikine is a peptide of Glycyl-Histidyl- Lysine or Glycyl-Glutaminyl-Prolyl-Arginine or a mixture thereof .

3. The cosmetic composition according to claim 1 or 2 , wherein said Phaseolus is of the Phaseolus lunatus kind.

4. The cosmetic composition according to any of claims 1-3, wherein comprising the matrikines Glycyl-Histidyl- Lysine and Glycyl-Glutaminyl-Prolyl-Arginine, rutin, Phaseolus lunatus extract, real aloe extract, vitamin E, sericin, Delesseria sanguinea extract, Saccharomices lysate, Chlorella alga extract, peptide with the amino-acid sequence Lys-Thr-Thr-Lys-Ser and a cosmetically accept- able carrier.

5. The cosmetic composition according to any of claims 1-4 having the following formulation: glyceryl stearate 1-5% cetylstearyl (12) OE 1-5% polysorbate 80 0.5-1% cetyl alcohol 1-3% octyldodecanol 1-3% cetylstearylisononanoate 1-3%

C_8-I0 triglyceride 10-20% diemthylpolysilyloxane 0.01-0.1% wheat germ oil 0.8% tocopheryl acetate 0.1% real aloe 0.010% matrikines : Glycyl-Histidyl-Lysine and Glycyl-Glutaminyl-Prolyl-Arginine 0.001% rutin 0.001%

Phaseolus lunatus extract 0.02% sericin 0.1% delesseria sanguinea extract 0.08% Chlorella alga extract 0.08%

Peptide (Lys-Thr-Thr-Lys-Ser) 0.002% saccharomices lysate 0.04% antioxidants and preservatives as sufficient water complement to 100

6. The cosmetic composition according to any of claims 1-4 having the following formulation: glyceryl stearate 2-5% cetylstearyl (12) OE 3-5% polysorbate 80 0.5-1% cetyl alcohol 2-3% octyldodecanol 3-4% butyl alcohol (26) OP (26) OE 0.8% cetylstearylisononanoate 2-3%

C_8-10 triglyceride 15-20% diemthylpolysilyloxane 0.08% wheat germ oil 0.8% tocopheryl acetate 0.2% real aloe 0.06% matrikines : Glycyl-Histidyl-Lysine and Glycyl-Glutaminyl-Prolyl-Arginine 0.001% rutin 0.01%

Phaseolus lunatus extract 0.02% sericin 0.2% delesseria sanguinea extract 0.25% Chlorella alga extract 0.3%

7. The cosmetic composition according to any of claims 1-4 having the following formulation: glyceryl stearate 4% cetylstearyl(12)OE 4% polysorbate 80 0.5% cetyl alcohol 3.5% octyldodecanol 2.8% butyl alcohol (26) OP (26) OE 3% cetylstearylisononanoate 2.5%

C_8-I₀ triglyceride 14% diemthylpolysilyloxane 0.08% wheat germ oil 1.0% tocopheryl acetate 0.35% real aloe 0.1% matrikines : Glycyl-Histidyl-Lysine and Glycyl-Glutaminyl-Prolyl-Arginine 0.002% rutin 0.01% Phaseolus lunatus extract 0.03% sericin 0.5% delesseria sanguinea extract 0.5% Chlorella alga extract 0.2% Peptide (Lys-Thr-Thr-Lys-Ser) 0.001% saccharomices lysate 0.65% citric acid 0.2% antioxidants and preservatives as sufficient water complement to 100 perfume

8. The cosmetic composition according to any of claims 1-7, in a form suitable for local application.

9. The cosmetic composition according to claim 8, in a form selected from emulsion, gel, cream, milk, oil, solution.

10. A cosmetic method for treating and/or preventing the formation of stretch marks on the skin comprising the local application of a cosmetically effective quantity of a composition according to any of the claims from 1 to 9.