Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q19/00—Preparations for care of the skin
  • A61Q19/08—Anti-ageing preparations
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
  • A61K36/02—Algae
  • A61K36/05—Chlorophycota or chlorophyta (green algae), e.g. Chlorella
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
  • A61K36/06—Fungi, e.g. yeasts
  • A61K36/062—Ascomycota
  • A61K36/064—Saccharomycetales, e.g. baker's yeast
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
  • A61K36/18—Magnoliophyta (angiosperms)
  • A61K36/185—Magnoliopsida (dicotyledons)
  • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
  • A61K36/18—Magnoliophyta (angiosperms)
  • A61K36/88—Liliopsida (monocotyledons)
  • A61K36/886—Aloeaceae (Aloe family), e.g. aloe vera
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K38/00—Medicinal preparations containing peptides
  • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
  • A61K38/08—Peptides having 5 to 11 amino acids
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/60—Sugars; Derivatives thereof
  • A61K8/602—Glycosides, e.g. rutin
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
  • A61K8/645—Proteins of vegetable origin; Derivatives or degradation products thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/67—Vitamins
  • A61K8/678—Tocopherol, i.e. vitamin E
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
  • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
  • A61K8/9706—Algae
  • A61K8/9722—Chlorophycota or Chlorophyta [green algae], e.g. Chlorella
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
  • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
  • A61K8/9783—Angiosperms [Magnoliophyta]
  • A61K8/9789—Magnoliopsida [dicotyledons]
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
  • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
  • A61K8/9783—Angiosperms [Magnoliophyta]
  • A61K8/9794—Liliopsida [monocotyledons]

Definitions

• 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”
• striae distensae or “striae atrophicae”
• 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.
• 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.
• Stretch marks strike females with a frequency which is twice that of males; they can appear at any age but mostly during puberty.
• 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.
• a biochemical-hormonal 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• a cosmetic composition 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 .
• 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 .
• 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.
• composition of the invention not only has the cosmetic properties indicated above but also the capacity of improving the microcirculation of the skin.
• 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.
• the following products are conveniently present
• 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.
• matrikines containing peptide fragments with 3 or 4 amino acids 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
• 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.
• IL6 interleukin 6
• a test in vivo has shown the toning (+19%) , elasti- cizing (+17%) and hydrating (+24%) activity of the tetrapeptide .
• 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.
• 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 .
• 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.
• 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
• 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.
• 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.
• TEWL Trans Epidermal Water Loss
• hydrophilic derivative of ⁇ -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.
• PGE2 prostaglandins E2
• COX-2 cyclo-oxygenase 2
• 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.
• Sericin 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.
• Sericin 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.
• Sericin increases the adhesion and growth of fibroblasts under culture.
• Delesseria sanguinea used as extract in an embodiment of the composition of the invention, is a red alga of the Rodoficee group.
• 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 :
• 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) .
• 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.
• 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:
• 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) .
• 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.
• hydrosoluble vitamins Bl, B2, B12, PP
• they 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 .
• 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) .
• Lys-Thr-Thr-Lys-Ser typi- cally 100 ppm
• 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.
• glycosaminoglycanes Another important category of molecules whose production is stimulated by the Peptide is that represented by glycosaminoglycanes .
• 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) .
• a method 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.
• matrikines s
• rutin 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.
• Aloe is also important as it stimulates the formation of the epidermal tissue.
• vitamin E helps to restore the elasticity of the skin which in this way is more resistant to stretching and mechanical stress .
• 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 .
• 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%
• 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 3 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 .
• 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 makes the skin more hydrated - the product 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.

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