EP3923903A1

EP3923903A1 - Cosmetic and/or dermatological composition for combating stretch marks

Info

Publication number: EP3923903A1
Application number: EP20705238.2A
Authority: EP
Inventors: Jacques Peyrot; Jean-Marie Lefevre; Philippe Humbert
Original assignee: Dermaconcept JMC SARL
Current assignee: Laboratoires Noreva Led
Priority date: 2019-02-12
Filing date: 2020-01-23
Publication date: 2021-12-22
Also published as: WO2020165514A1; FR3092493A1

Abstract

The present invention relates to a cosmetic and/or dermatological composition for topical application, comprising: - hyaluronic acid, or a salt thereof, having a molecular weight of at most 1000 kDa, - ascorbic acid or a derivative thereof, and - an extract of Peucedanum graveolens.

Description

Title of the invention: Cosmetic and / or dermatological composition for combating stretch marks

The present invention relates to a cosmetic and / or dermatological composition intended for preventing and / or treating the appearance of stretch marks on the skin.

Stretch marks are cutaneous streaks which appear in particular following an exaggerated distension of the skin, for example during weight gain, pregnancy, and / or a hormonal change, for example during puberty, and concern especially women.

Stretch marks can be localized on the front of the abdomen, on the breasts, thighs and hips.

They form parallel and elongated cutaneous streaks, the color of which can vary from pale pink to purplish red (immature or inflammatory stretch marks). They tend to change color over time and take on a pearly white appearance (mature stretch marks). They then become less noticeable, but the scar may remain.

As indicated above, stretch marks can arise under the effect of too rapid and sudden stretching of the skin: it is therefore the dermal tissue that is damaged, the target cell of these attacks being the fibroblast.

There are many dermatological and / or cosmetic compositions intended for combating stretch marks. In this regard, mention may be made of application WO 00/19974 comprising an anti-stretch mark agent which may be soybean peptides or tripeptides consisting of the amino acids glycine, histidine and lysine.

However, despite the various dermatological and / or cosmetic compositions available, there still exists a need to be able to have available new alternative compositions having new beneficial effects. As such, a new cosmetic and / or dermatological composition has been discovered by the Applicant. The first subject of the present invention is a composition

cosmetic and / or dermatological, in particular for topical application, comprising:

- hyaluronic acid, or a salt thereof, having a molecular weight of at most 1000 kDa,

- ascorbic acid or one of its derivatives, and

- an extract of Peucedanum graveolens.

Preferably, the composition of the first object can be used, in particular in non-therapeutic use, for the prevention and / or treatment of stretch marks on the skin.

A second subject of the present invention is a composition for its application as a medicament for the prevention and / or treatment of stretch marks on the skin, comprising:

- ascorbic acid or one of its derivatives, and

- an extract of Peucedanum graveolens.

Preferably, the composition of the second object can be formulated for topical application.

The composition according to the invention advantageously makes it possible to prevent and / or treat the appearance of stretch marks on the skin, while guaranteeing non-irritant properties for the skin.

In the present invention, the expression “prevention of stretch marks on the skin” is understood to mean an action making it possible to reduce, or even avoid, the formation of stretch marks in the context of a cosmetic and / or dermatological treatment, by application. of the composition, before and during an event known to cause the appearance of stretch marks.

In the present invention, the expression “treatment of stretch marks on the skin” is understood to mean an action making it possible to regress, or even to absorb, in the context of a cosmetic and / and dermatological treatment, in a visible and measurable manner, stretch marks already formed

The reduction or absorption of stretch marks is more particularly an action on their length, their width and / or their depth. Thus, the composition used according to the invention can be applied topically to areas of the skin liable to form stretch marks, comprising stretch marks in the course of formation or even comprising stretch marks already formed. These areas are well known to those skilled in the art, and may correspond to the area of the stomach, hips, buttocks, thighs and / or breasts.

Hyaluronic acid or one of its salts

Hyaluronic acid is a natural glycosaminoglycan-type disaccharide-based polymer comprising D-glucuronic acid and N-acetylglucosamine units linked by glucosidic linkage.

It can be in free, hydrolyzed form, or else in the form of one of its salts, such as alkali metal and alkaline earth metal salts, for example sodium, potassium, calcium or magnesium hyaluronate.

The hyaluronic acid usable in the invention is commercially available in various forms suitable according to the intended uses. It can be produced industrially in large quantities by extraction from animal tissues such as rooster ridges, or by bacterial fermentation, or else by biotechnological process from plant substances, for example wheat.

The properties of hyaluronic acid vary greatly depending on its molecular weight. Hyaluronic acid, or a salt thereof, by weight

molecular weight of at most 1000 kDa (i.e. low molecular weight) has the advantage of being able to cross the barrier of the stratum corneum and thus stimulate

CD44 receptors responsible for the neosynthesis of hyaluronic acid in the dermis.

Hyaluronic acid, or one of its salts, can have a weight

molecular weight of at least 50 kDa, preferably at least 100 kDa, and preferably at least 300 kDa.

Hyaluronic acid, or one of its salts, can also have a molecular weight of at most 800 kDa, and preferably at most 500 kDa.

Particularly preferably, hyaluronic acid, or one of its salts, can have a molecular weight ranging from 300 kDa to 500 kDa. The studies carried out by the Applicant have shown that the choice of a hyaluronic acid meeting this condition allows an action in the epidermis, leading to an improvement in keratinocyte function, without directly affecting the dermis.

The composition of the invention may comprise an effective amount of hyaluronic acid or one of its salts, the effective amount being that which is necessary to obtain the effects expected according to the invention.

By way of example, the composition of the invention may comprise from 0.01% to 5% by weight of hyaluronic acid or one of its salts, and of

preferably from 0.1% to 1% by weight of hyaluronic acid or one of its salts, relative to the total weight of the composition.

Ascorbic acid or one of its derivatives

Ascorbic acid (or vitamin C) is an organic acid,

usually in L form (i.e. L-ascorbic acid), as it is usually extracted from natural products such as lemons, oranges, etc.

The ascorbic acid derivatives can be chosen from salts, such as in particular sodium ascorbate, magnesium or sodium ascorbylphosphate; esters, such as in particular acetic esters,

propionic or palmitic; sugars, such as in particular glycosylated ascorbic acid; and one of their mixtures.

Ascorbic acid, or a derivative thereof, is preferably in a stabilized form. In other words, ascorbic acid, or one of its derivatives, is in a substantially non-oxidizable form, and in particular a form which can be transported by a lipid.

As an example of stabilized ascorbic acid (i.e. stable derivative of ascorbic acid), mention may be made of ethyl-ascorbic acid.

The composition of the invention may comprise an effective amount of ascorbic acid or one of its derivatives, the effective amount being that which is necessary to obtain the effects expected according to the invention.

By way of example, the composition of the invention may comprise from 0.01% to 5% by weight of ascorbic acid or one of its derivatives, and of preferably 0.1% to 2% of ascorbic acid or a derivative thereof, relative to the total weight of the composition.

Peucedanum qraveolens extract

A peucedanum graveolens extract is an extract from a plant of the genus Peucedanum graveolens, a plant also known as dill. The extract can be the plant as a whole, and / or one or more constituent elements of the plant such as a flower, a seed, a root, a rhizome, a stem, a fruit and / or a leaf. . The plant and / or the constituent elements of the plant can be prepared by grinding or chemical extraction well known to those skilled in the art.

In a preferred embodiment, the extract of Peucedanum

graveolens can be an extract from the fruit of Peucedanum graveolens.

Such compounds may also be isolated from the plant by using extraction procedures well known to those skilled in the art, for example using organic solvents such as lower alcohols, Ci-C ₈ alkyl polyols -C -C ₈ alkyl ketones, Ci-C _8, alkyl ethers Ci-C ₈ alkyl esters of Ci-C ₈ of acetic acid and chloroform, and / or by using inorganic solvents such as water, inorganic acids such as hydrochloric acid, and inorganic bases such as sodium hydroxide. The solvent for the extraction procedures is preferably an inorganic solvent, and particularly preferably water: the extract of Peucedanum graveolens can thus advantageously be an aqueous extract.

A particularly suitable extract of Peucedanum graveolens can be a product commercially available from BASF Beauty Care Solutions, under the reference Lys'Lastine, this product comprising an extract of Peucedanum graveolens in an amount of 5% to 10% by weight per relative to the total weight of said product.

The composition of the invention may comprise an effective amount of extract of Peucedanum graveolens, the effective amount being that which is necessary to obtain the effects expected according to the invention. By way of example, the composition of the invention may comprise from 0.001% to 2% by weight of extract of Peucedanum graveolens, and of

preferably from 0.005% to 1% by weight of Peucedanum graveolens extract, relative to the total weight of the composition of the invention.

The compositions in accordance with the present invention can be presented in the forms conventionally used for topical application, that is to say in the form of a gel, lotion, emulsion (in particular cream or milk), spot-on, serum (or essence), mask or ointment, containing the usual compatible and pharmaceutically acceptable excipients and carriers. They may also be in the form of patches, tulles or controlled-release dressings, or of wipes soaked in a composition according to the invention.

These topical administration forms are prepared by techniques well known to those skilled in the art, and for example, in the case of a cream, by dispersing a fatty phase in an aqueous phase to obtain an oil emulsion. in water, or vice versa to prepare a water-in-oil emulsion.

The composition according to the invention may comprise one or more usual excipients, suitable in particular for external topical administration, in particular dermatologically and / or cosmetologically acceptable excipients.

These excipients suitable for the formulation are well known to those skilled in the art, and can be chosen, for example, from one or more of the compounds i to xv listed below:

i. antioxidant vitamins, other than vitamin C or a derivative thereof, such as vitamin E, for example tocopherol acetate or tocotrienol; natural polyphenols;

ii. buffers, such as citric acid or a salt thereof; sodium hydroxide;

iii. vegetable oils such as for example Kukui oil, Calophyllum Inophyllum oil, Helichrysum oil,

Macadamia, Inca inchi oil, prickly pear oil, oil argan;

iv. gelling agents and / or thickeners, such as natural gums such as xanthan gum; synthetic polymers, for example

polyacrylamides of the Carbopol type, crosslinked acrylate polymers and cellulose derivatives; sodium acrylate copolymers;

v. emulsifiers and co-emulsifiers, such as arachidyl glucoside;

cetearyl glucoside; behenyl alcohol; cetearyl alcohol; cetostearyl alcohol; cetyl alcohol, steareth-2; steareth-21; isostearyl isostearate;

isopropyl myristate, sorbitan esters and polysorbates; hydrophilic polymer of acrylic acid (e.g. carbomer);

vi. emollients and surfactants, such as octyl dodecanol; isononyl isononanoate; capric / caprylic triglycerides; cetearyl octanoate; isopropyl myristate; cetearyl isononanoate; polyglyceryl 3-diisostearate; hydrogenated polyisobutene; cetyl palmitate; cetyl phosphate; vegetable oils such as macadamia oil; lecithin; glyceryl caprylate;

vii. silicones such as dimethicone, cyclomethicone;

viii. humectants / moisturizers, such as glycerin; butylene glycol; propylene glycol;

ix. preservatives, such as phenoxyethanol, dehydroacetic acid; benzoic acid; potassium sorbate; sodium benzoate; methyl or ethyl parahydroxybenzoates; chlorophenesin;

x. agents for protecting against ultraviolet rays, such as hydrophilic or lipophilic UV-A and UV-B sunscreens, chosen from

benzophenone or a benzophenone derivative such as 2-hydroxy-4-methoxy-benzophenone; an ester of cinnamic acid, and more particularly octyl methoxycinnamate and ethyl-2-hexyl methoxycinnamate, or alternatively a cyano-b, b-diphenylacrylate such as octo-crylene, 4-methylbenzylidene camphor , and dibenzoylmethane derivatives such as 4-isopropyl dibenzoylmethane, t-butyl-methoxy dibenzoylmethane, and 4-methoxy-dibenzoylmethane; or such as pigments forming a UV screen; xi. exfoliating powders; fruit powders; or powders

mattifying agents such as methyl methacrylate copolymer; xii. neutralizing agents;

xiii. solubilizers;

xiv. dyes; and or

xv. perfumes.

The composition according to the invention can also comprise one or more usual additional active agents, suitable in particular for a

external topical administration, in particular active ingredients which are dermatologically and / or cosmetologically acceptable.

These complementary active agents suitable for the formulation are well known to those skilled in the art, and can be, for example, anti-aging agents, soothing active ingredients, purifying active ingredients, moisturizing active ingredients, antimicrobial active ingredients, etc.

A third subject of the present invention is a use of an extract of Peucedanum graveolens, and more particularly a non-therapeutic use of an extract of Peucedanum graveolens, for the prevention and / or treatment of stretch marks on the skin. Preferably, said extract is used in topical application.

Other characteristics and advantages of the present invention will become apparent in the light of the examples which follow, said examples being given by way of illustration and in no way limiting.

Exem pies

1. Evaluation of the effect of the composition of the invention on fibroblasts of red stretch marks in the GlasBox ^plus® system

Comparative tests were carried out to show the effect of the composition according to the invention on the contractile forces of fibroblasts with red stretch marks (immature or inflammatory stretch marks).

1.1. Procedure

1.1.1. Active compounds

The active compounds are collated in Table 1 below:

[Table 1]

Your blea u 1

(*) The Lys'Lastine compound mainly comprises water and approximately 7.5% by weight of Peucedanum graveolens extract relative to the total weight of said compound.

The assets are diluted directly in a culture medium as described below.

1.1.2. Obtaining and culturing fibroblasts

A 2 mm diameter biopsy was taken from a red stretch mark from a 22-year-old man.

The classic explantation technique is used for the extraction of fibroblasts. The explant is cultured in "Dulbecco's modified Eagle's medium" medium supplemented with 10% fetal calf serum (FCS), 40 mg / l of gentamicin and 2 mg / l of fungizone (DMEMc) at 37 ° C. , in a humid atmosphere and in the presence of 5% C0 ₂ . Gradually, in about ten days, the fibroblasts migrate outside the explant. The culture medium is renewed twice a week. When the fibroblasts are in sufficient quantity, they are detached under the action of trypsin-EDTA, subcultured and amplified under the same culture conditions.

1.2. Study of isometric forces in the GlasBox ^plus® system

1.2.1. Overview of the GlasBox ^{plus® System} The equivalent dermis develop in a culture dish which consists of eight rectangular tanks. In each of them plunge two flexible blades, the lower parts of which are made up of grids on which the equivalent dermis clings during its polymerization. The equivalent dermis develops between two blades to result in a shape

rectangular slightly narrowed in the center. This shape in classical mechanics is referred to as a "diabolo" shape.

Under the influence of contractile forces (or contraction forces) developed by fibroblasts, the laminae become deformed. Their deformation is measured using optical fibers. This deformation is proportional to the force developed within the equivalent dermis. The measurements are carried out in real time using a PC acquisition card and suitable software.

1.2.2. Preparation of equivalent dermis under tension and measurement of isometric forces

The fibroblasts cultured in a monolayer and treated or not are trypsinized and then counted to bring the cell suspension to

8105 cells / ml. A medium for manufacturing equivalent dermis is prepared by mixing:

- 6 volumes of 1.76X medium (DMEMc, NaHCO3, NaOH, antibiotics, SVF),

- 3 volumes of rat tail type I collagen (2 mg / ml), and

- 1 volume of cell suspension (8105 cells / ml).

The mixture is poured into the rectangular tanks of the GlasBox ^plus® . In a few minutes at 37 ° C, a gel is formed. The culture medium containing or not the active compounds is added and the isometric forces are measured for 24 hours.

The test groups are as follows:

- Control (i.e. culture medium without active compound);

- AH (0.1%);

- AA (0.1%);

- PG (0.1%);

- Comparative mixture (Mixture C): HA (0.1%) + AA (0.1%); and - Mixture according to the invention (Mixture I): AH (0.1%) + AA (0.1%) + PG

(0.1%).

The amounts expressed in parentheses correspond to amounts by weight relative to the total weight of the culture medium.

1.2.3. Statistical calculations and analyzes

Values are expressed as the mean ± standard error of the distribution of means (wk).

For the study of contractile forces, curves presenting the contractile forces as a function of time were obtained, the areas under the curves (AUC) are calculated as well as the maximum of contraction (Max), all using the software GraphPad Prism ^® . AUC provides information on the overall effect of treatment on contractile forces. The maximum contraction corresponds to the plateau of the curves. For these data, a one-way analysis of variance is performed, followed if necessary by a Fisher test.

1.3. Study of the contractile forces of red stretch mark fibroblasts

1.3.1. Study of the effect of AH

The results are collated in Table 2 below:

[Table 2]

Your blea u 2

The AUC and the Max are not significantly modified in the presence of 0.1% by weight of HA relative to the Control (decrease of approximately 4%).

1.3.2. Study of the effect of AA

The results are collated in Table 3 below:

[Table 3]

Your blea u 3

The AUC and the Max are not significantly modified in the presence of 0.1% by weight of AA relative to the Control (decrease of approximately 1%).

1.3.3. Study of the effect of the compound based on PG

The results are collated in Table 4 below:

[Table 4]

Your skin 4

The AUC and the Max are not significantly modified in the presence of 0.1% by weight of PG relative to the Control (decrease of approximately 4.5%).

1.3.4. Study of the effect of Mixture C

The results are collated in Table 5 below:

[Table 5]

Your skin 5 The AUC and the Max are not significantly modified in the presence of Mixture C (AH (0.1%) + AA (0.1%)) relative to the Control (decrease of approximately 4.5%).

1.3.5. Study of the effect of Mixture I

The results are collated in Table 6 below:

[Table 6]

Table 6

A significant decrease in AUC and Max is observed in the presence of Mixture I (HA (0.1%) + AA (0.1%) + PG (0.1%)) compared to Control (decrease in about 14%).

1.3.6. Conclusion

The active compounds AA, AH or PG used alone have little or no effect on the contractile forces of red stretch mark fibroblasts. Mixture C also has very little effect on the development of contractile forces.

On the other hand, Mixture I in accordance with the invention allows a very significant reduction in contractile forces and thus significantly limits or even prevents the rupture of stretch mark fibroblasts. Thus, Mixture I has significant anti-stretch mark properties.

2. Cosmetic and / or dermatological composition based on an extract of

Peucedanum qraveolens, according to the invention According to conventional techniques, a gel based on a composition according to the invention is prepared, the constituents of this composition being collated in Table 7 below:

[Table 7]

Your blea u 7

The amounts of the various constituents of the composition in Table 7 are expressed in% by weight relative to the total weight of the composition.

The origin of the constituents of the composition of Table 7 is as follows:

- Hyaluronic acid is a hyaluronic acid of 450 kDa, marketed by the company Soliance, under the reference Primalhyal 450;

- Ascorbic acid is vitamin C stabilized in the form of ethyl-ascorbic acid, marketed by the company Safic-Alcan under the reference ET-VC

; and - Compound based on an extract of Peucedanum graveolens is the compound marketed by the company BASF Beauty Care Solutions, under the reference Lys'Lastine, this compound comprising approximately 7.5% by weight of extract of Peucedanum graveolens relative to the weight total of said compound; this compound further comprises solvents (water in an amount of 67% by weight, and penthylene glycol in an amount of 7.5% by weight), 0.5% by weight

thickener and 17.5% by weight of humectant, relative to the total weight of said compound.

The other constituents cited in Table 7, such as: humectant, emollient, thickener, emulsifier, preservative and buffer, are conventional excipients such as, for example, those mentioned in the present invention.

This gel can be easily applied in particular to the stomach, hips, buttocks, thighs and / or breasts.

To treat stretch marks, this gel can be applied two to three times a day, preferably every 8 hours, and for at least 8 weeks, until satisfactory results are obtained.

To prevent the appearance of stretch marks, the gel described above can be applied at least once or twice a day, for example in the morning and / or in the evening, for at least 12 weeks, and preferably for at least 24 weeks. .

Claims

[Claim 1] Cosmetic and / or dermatological composition, for

topical application, comprising:

- hyaluronic acid, or a salt thereof, with a molecular weight of not more than 1000 kDa,

- ascorbic acid or one of its derivatives, and

- an extract of Peucedanum graveolens.

[Claim 2] Composition for its application as a medicament for the prevention and / or treatment of stretch marks on the skin,

including:

- ascorbic acid or one of its derivatives, and

- an extract of Peucedanum graveolens.

[Claim 3] A composition according to claim 2 formulated for topical application.

[Claim 4] Composition according to any one of the preceding claims, characterized in that the hyaluronic acid, or a salt thereof, has a molecular weight of at least 50 kDa.

[Claim 5] Composition according to any one of the preceding claims, characterized in that the hyaluronic acid, or a salt thereof, has a molecular weight of at most 800 kDa.

[Claim 6] Composition according to any one of the preceding claims, characterized in that it comprises from 0.01% to 5% by weight of hyaluronic acid or a salt thereof, relative to the total weight of the composition.

[Claim 7] Composition according to any one of the preceding claims, characterized in that it comprises from 0.01% to 5% by weight of ascorbic acid or one of its derivatives, relative to the total weight of the composition.

[Claim 8] Composition according to any one of the preceding claims, characterized in that it comprises from 0.001% to 2% by weight of extract of Peucedanum graveolens, and preferably from 0.005% to 1% by weight of extract of Peucedanum graveolens, relative to the total weight of the composition.

[Claim 9] Composition according to any one of the preceding claims, characterized in that the ascorbic acid derivative is chosen from salts of ascorbic acid, esters of acid

ascorbic, and a mixture thereof.

[Claim 10] Composition according to any one of the preceding claims, characterized in that the extract of Peucedanum graveolens is an extract of the fruit of Peucedanum graveolens.

[Claim 1 1] Composition according to any one of the preceding claims, characterized in that the extract of Peucedanum graveolens is an aqueous extract.

[Claim 12] Non-therapeutic use of the composition according to any one of claims 1, 4 to 11, for the prevention and / or treatment of stretch marks on the skin.

[Claim 13] Non-therapeutic use of an extract of Peucedanum graveolens for the prevention and / or treatment of stretch marks on the skin, preferably topically.