WO1996028008A2

WO1996028008A2 - Novel cosmetic or dermatological compositions for controlling skin ageing

Info

Publication number: WO1996028008A2
Application number: PCT/FR1996/000811
Authority: WO
Inventors: Catherine Heusele; Jacques Le Blay
Original assignee: Guerlain S.A.
Priority date: 1996-03-19
Filing date: 1996-05-30
Publication date: 1996-09-19
Also published as: AU6227796A; WO1996028008A3; FR2746316A1; FR2746316B1

Abstract

Novel compositions for controlling skin ageing and/or increasing skin elasticity are disclosed. The compositions include two active principles of which one affects the formation of Amadori products while the other inhibits elastase activity. Said novel compositions are particularly suitable for cosmetic or dermatological use.

Description

NEW COSMETIC OR DERMATOLOGICAL COMPOSITIONS

The invention relates to a new cosmetic or dermatological composition intended to combat aging of the skin and / or to increase the elasticity of the skin.

The aging of the skin is a complex phenomenon, involving many more or less slow reactions and which lead to a decrease in skin elasticity and the appearance of wrinkles.

These changes in biomechanical properties are mainly due to the evolution of two of the main macromolecules of the dermis, collagen and elastin.

It is in fact known that collagen is renewed more slowly at the time of aging and that the replacement of aged fibers becomes more difficult, in particular due to the appearance of internal cross links forming bridges between the collagen fibers.

These connections, the number of which increases with age, participate in the stiffening and stiffening of the tissues, which are characteristic phenomena of an aging tissue.

It has also been shown that these bridging bonds originate in particular from a fixation of glucose on the collagen, in particular on the lysine and hydroxylysine residues of the latter (ref. 1).

This non-enzymatic fixation of glucose is known under the name of glycation and has been demonstrated for a long time, in particular by the work of Maillard. Since then, the fixation of other sugars, such as fructose or ribose, has also been shown.

The binding of glucose to proteins involves a series of reactions including the formation of unstable Schiff bases which rearrange into more stable products, known as Amadori products. Over time, these Amadori products can then react with a variety of molecules, to finally give irreversible structures after rearrangement. In the case of glucose, experiments have shown that one of the irreversible products ultimately formed is [2- (2-furoyl) -4 (5) - (2-furanyl) -1H- imidazole].

This product is yellowish brown and fluorescent.

In the case of glucose, a correlation has been established between the increase in the glycation rate and the increase in the tensile strength of collagen (ref. 2) as well as a decrease in its solubility (ref. 3) , establishing the harmful role of these glycation products in the mechanical properties of collagen.

It is also known that the fixation of glucose on proteins leads, in the presence of oxygen, to the formation of free radicals (ref. 4). The destructive effects of free radicals on the various constituents of the skin are well known: lipid peroxidation, cutting of proteins and glycosaminoglycans, bridging between tyrosine residues and proteins, etc. Due to these degradations, the appearance of free radicals also constitutes an aging factor of the skin tissue.

Finally, if the glycation of collagen takes place in an oxidizing medium, other types of bypass are also formed. For example, fructolysine is itself degraded into N- (carboxymethyl) lysine or is transformed, after reaction with an arginine residue, to finally give pentosidine.

These bypasses resulting from protein glycoxyation also increase with age in humans (ref. 5).

It was then proposed to use substances preventing Amadori products from rearranging over time into irreversible products. It has been shown in particular that aminoguanidine decreases the crosslinking of proteins contained in the arterial walls of diabetic subjects. Aminoguanidine works by blocking the transformation of Amadori products resulting from the rearrangement of glucose and a protein into [2- (2-furoyl) -4 (5) - (2-furanyl) -1H-imidazole] (ref . 6). In addition, it has long been known that elastases are the enzymes responsible for the degradation of elastin by hydrolysis (ref. 7) and that therefore elastases also contribute to the degradation of the elastic properties of the skin.

Two types of elastases can be found in the skin. First of all, the leukocyte elastase is released by polymorphonuclear cells following the exposure of the skin to tension or stress, in particular ultraviolet radiation, pollution, infection, etc. (ref. 8). On the other hand, elastases belonging to the class of metalloproteases are synthesized by fibroblasts of the dermis and this in an increasing manner with age (ref. 9).

The bridging of collagen by glycation and the stiffening of the fibers which results therefrom on the one hand, the destruction of the elastin fibers under the effect of the elastases on the other hand, are two phenomena whose conjugation causes a loss of elasticity of the dermis which leads to the formation of wrinkles and fine lines. It is therefore important to act simultaneously on the two phenomena to restore adequate skin elasticity and combat the appearance of wrinkles.

Although the use of compounds such as aminoguanidine already shows an anti-glycation action, the inventors of the present patent application have sought to improve the results obtained.

The main aim of the present invention is therefore to provide a new cosmetic or dermatological composition with improved anti-glycation and anti-elastase combined action and making it possible to avoid the formation of free radicals.

Another object of the present invention relates to the use of anti-glycation compounds and anti-elastase compounds for the preparation of a cosmetic composition.

The composition according to the present invention, with a view to combating aging and / or increasing the elasticity of the skin, is characterized in that it comprises a first active principle chosen from natural or synthetic compounds capable of inhibiting the formation of Amadori products by reaction non-enzymatic of sugars, in particular glucose, with the collagen of the skin, said first active principle consisting of a single compound or of a mixture of several compounds; and in that it comprises a second active principle chosen from natural or synthetic compounds capable of inhibiting the activity of skin elastases, said second active principle consisting of a single compound or of a mixture of several compounds .

The present invention results from the surprising discovery that certain products can block the glycation of proteins at a stage prior to that of the formation of Amadori products.

In this way, the mechanism of degradation of collagen by glycation, can be blocked even earlier than before and thus allows to obtain better results on the elasticity of the skin.

According to the invention, the first active principle is chosen in particular from amino acids, preferably basic, in particular lysine, arginine, histidine; peptides, preferably those containing one or more basic amino acids; allantoin; vitamin E; vitamin B ₁ ; vitamin B ₆ ; thiourea; dithiothreitol; organic silicon derivatives and / or derivatives of these products.

According to a preferred embodiment of the present invention, the amino acid derivatives include in particular lysine pyrrolidone carboxylate, arginine pyrrolidone carboxylate, arginine aspartate.

According to the invention, the second active principle is chosen from compounds capable of blocking the action of leukocyte elastase and / or elastases synthesized by fibroblasts. It is chosen in particular from plant extracts rich in tannins, in anthocyanosides, procyanidolic oligomers, soy extract, in particular soy protein extracts, α-1-anti-trypsin, algae extracts, especially hydrolysates of green algae proteins and micro algae extracts, polysaccharides, in particular sulfated polysaccharides, ceramides. According to the invention, the composition comprises, as a percentage by weight relative to the total weight of the composition, from approximately 0.01% to approximately 50% by weight of said first active principle, preferably from approximately 0.1% to about 10% by weight, more preferably from about 0.2% to about 5% by weight and from about 0.01% to about 50% by weight of said second active ingredient, preferably from about 0.1% to about 10% by weight, more preferably from about 0.5% to about 5% by weight.

According to a preferred embodiment of the present invention, the composition further comprises at least one natural or synthetic compound activating the synthesis of collagen, in particular an extract of Centella asiatica, ascorbic acid, peptides, β-glucans or seaweed or oat extracts containing them, or derivatives of these products.

Advantageously, the concentration of compound activating the synthesis of collagen varies from approximately 0.01% to approximately 10% by weight, preferably from approximately 0.05% to approximately 5% by weight relative to the total weight of the composition. .

According to another preferred embodiment of the present invention, the composition further comprises at least one natural or synthetic compound capable of preventing the production of free radicals, thus improving the inhibitory properties of the formation of free radicals of the first active principle.

Mention will be made, by way of illustration of compounds capable of preventing the formation of free radicals which can be used in the context of the present patent application, vitamin E or its esters, vitamin C, plant extracts rich in flavonoids or polyphenols, such as Ginkgo biloba, green tea, thistle, etc., caffeic acid, ferulic acid, glutathione, enzymes such as superoxide dismutase, glutathione reductase and glutathione peroxidase, zinc salts, mannitol or a derivative of these products.

Advantageously, the concentration of compound inhibiting the production of free radicals varies from approximately 0.01% to approximately 20% by weight, preferably from about 0.1% to about 5% by weight relative to the total weight of the composition.

According to another preferred embodiment of the present invention, the composition further comprises at least one natural or synthetic hydrating compound, in particular polyols, a constituent of the natural hydration factor

(Natural Moisturing Factor or NMF) such as urea, an amino acid, a honey extract, hyaluronic acid, a mucopolysaccharide, one of the constituents of intercellular cement such as ceramides, fatty acids, cholesterol , etc., phospholipids or a derivative of these products.

Advantageously, the concentration of hydrating compound varies from approximately 0.1% to approximately 30% by weight, preferably from approximately 0.5% to approximately

10% by weight relative to the total weight of the composition.

Advantageously, the composition according to the invention also comprises one or more preservatives, sun filters, excipients, stabilizing agents and / or perfumes such as those conventionally used in the cosmetics industry.

According to a preferred embodiment of the present invention, the composition comprises, in percentage by weight relative to the total weight of the composition:

- from about 0.1% to about 10% of lysine pyrrolidone carboxylate;

- from about 0.1% to about 5% of a soy extract having anti-elastase activity;

- from about 0.1% to about 5% of a mixture of plants with anti-elastase activity.

According to another preferred embodiment of the present invention, the composition comprises, in percentage by weight relative to the total weight of the composition:

- from about 0.1% to about 10% of arginine aspartate;

- from approximately 0.01% to approximately 2% of procyanidolic oligomers. According to another preferred embodiment of the present invention, the composition comprises, in percentage by weight relative to the total weight of the composition:

- from about 0.1% to about 5% of L-histidine;

- from about 0.1% to about 5% of a soy extract with anti-elastase activity;

from about 0.1% to about 5% of an algae extract with anti-elastase effect.

- from about 0.1% to about 5% of L-lysine pyrrolidone carboxylate;

- from about 0.1% to about 5% of arginine aspartate;

- from about 0.1% to about 10% of a soy extract with anti-elastase effect.

The compositions according to the invention are particularly well suited for cosmetic or dermatological use. As such, they can be in all the dosage forms usually used for these products, namely in particular aqueous, alcoholic or hydroalcoholic solution, water-in-oil or oil-in-water emulsion, composition in aerosol form, powder. , microgranulate, dispersion, lotion, ointment. These compositions are prepared according to the usual methods of the fields considered.

The compositions according to the invention notably constitute cleaning, protection, treatment or care compositions for the face, for the hands or for the body, for example day cream, night cream, make-up remover cream, anti-aging serum , body milk, cleansing milk, after-sun milk, cleansing milk, sun cream or oil, face or body gel, regenerating anti-wrinkle product, makeup composition, self-tanning composition, bath composition. The compositions according to the invention can also consist of solid preparations such as soaps or cleaning bars.

They can also be used in various compositions for the hair, in particular shampoos, styling lotions, treating lotions, styling creams or gels, dye compositions, lotions or hair loss gels.

Additional advantages and characteristics of the present invention will become apparent in the light of the more detailed description which follows of particular embodiments of the invention, given by way of illustration and not limitation.

Example 1.

Preparation of a face cream

A composition comprising the following ingredients (in percentage by weight relative to the total weight of the composition) is prepared as described below.

Preparation:

After mixing the various constituents which compose it, phase 1 is heated to 80 ° C. with stirring in a melter.

The Carbomer contained in phase 2 is dispersed in water at 90 ° C with stirring then is poured into a mixer where it is neutralized by triethanolamine. The other constituents of phase 2 are then added and the mixture is brought to 80 ° C. with stirring.

Phase 1 is poured onto phase 2 in the mixer with vigorous stirring, then the mixture is cooled with stirring. The various constituents of phase 3 are mixed and then phase 3 thus obtained, previously homogenized, is added at 60 ° C. Finally, phase 4 is prepared by mixing its constituents and then is introduced into the mixer at 40 ° C. Agitation is stopped when the product temperature reaches 25 ° C.

Example 2.

Preparation of a cream for the night. A composition comprising the following ingredients (in percentage by weight relative to the total weight of the composition) is prepared as described below.

Preparation:

The gelling agents contained in phase 2 are dispersed in water at 90 ° C with stirring then the gel formed is poured into a mixer. The other constituents of phase 2 are added and the mixture is brought to 80 ° C. with stirring.

Phase 1 is poured onto phase 2 in the mixer with vigorous stirring, then the mixture is cooled with stirring. Phase 3 previously prepared and homogenized is added at 60 ° C. Finally, phase 4 is prepared by mixing its constituents and then is introduced into the mixer at 40 ° C. Agitation is stopped when the product temperature reaches 25 ° C.

Example 3.

Preparation of a face cream.

The method of preparation is identical to that described in Example 1. Experimental results,

a) Demonstration of the anti-glycation action.

In this experiment, the binding of glucose to collagen and bovine serum albumin is studied.

To do this, 0.25 mg / ml of collagen or 0.25 mg / ml of bovine serum albumin are incubated for 0, 4 and 10 days, with amounts of radioactive glucose of 0, 5, 50 and 200 mM at 37 ° C in a total volume of 4 ml of 50 mM phosphate buffer pH 7.4, in closed sterile tubes. At the end of the incubation period, the Schiff bases obtained by reaction between glucose and the amino residues of collagen or bovine serum albumin are reduced by adding 1 ml of a 2 mM solution of sodium borohydride tritiate. The reaction mixture obtained is then dialyzed at 4 ° C for 48 hours against distilled water, to remove the glucose and NaBH ₄ not attached to the proteins.

Radioactivity bound to proteins after dialysis is counted using a liquid scintillation counter.

The same experiment is carried out in parallel by adding 200 mM of L-lysine hydrochloride to the starting collagen or bovine albumin serum.

Tables I and II appearing in the appendix to this patent application illustrate the results. It appears from Table I that the fixation of glucose alone on serum albumin increases over time, passing from a measured radioactivity value of 4920 cpm at tO to a value of 11350 cpm after 10 days.

The addition of lysine hydrochloride prevents the fixation of glucose, the radioactivity measured passing from a value of 4320 cpm at tO to a value of 4515 cpm after 10 days.

The results are identical in Table II which shows that the addition of lysine hydrochloride prevents the binding of glucose to the collagen.

The results obtained therefore show that, in the tubes not containing L-lysine, the glucose fixes itself on the collagen or on the bovine serum albumin whereas in the tubes where L-lysine was added to the proteins, the fixation glucose on collagen or bovine serum albumin is completely inhibited.

b) Effects of the compositions of the invention on the aging and elasticity of the skin.

The effect of composition 1 on the aging of the skin has been studied.

In this test, the viscoelastic characteristics of the skin were measured.

The biomechanical properties of the skin are evaluated using a Dermal Torque Meter measuring device (company Diastron, Great Britain). This device includes a probe which allows torsion to be exerted on the skin with constant torque, the angle formed being measured as a function of time. The recording is also performed after the constraint is released.

Composition 1 is applied to the forearm of 20 volunteers, the other forearm serving as a control. The dose of product applied to the skin corresponds to the normal dose for use and is between 1 and 2 mg / cm ² .

The measurements are carried out before application of the composition and after 15 days, 30 days and 45 days of daily treatment.

The biomechanical properties are evaluated 12 to 15 hours after application of the composition.

The viscoelastic behavior of the skin can be determined by the following characteristics.

U _E : Instantaneous angular deviation (at 0.05 seconds) corresponding to the elastic extensibility of the skin subjected to a constant torque of 1 lmNm.

U _V : Viscoelastic extensibility of the skin corresponding to the plastic deformation of the skin between 0.05 and 30 seconds.

U _F : Total extensibility of the skin including elastic extensibility (U _E ) and viscoelastic extensibility (U _V ). This total extensibility value is measured 30 seconds after the start of the application of a torque of 11mNm.

U _R : Immediate elastic recovery after the torsion applied to the skin has stopped.

The results, expressed in relation to time and to the control, are given in Tables III to V appearing in the appendix to this patent application.

Referring to Table III, it appears that the elastic extensibility (U _E ) of the skin is significantly improved during the treatment, reaching an increase of + 41.3% after 45 days.

Referring now to Table IV, it appears that the U _V / U _E ratio decreases, signifying that the skin firmness during the application of the stress is also improved, decreasing to a value of - 24.2% at after 45 days. Referring finally to Table V, it appears that composition 1 also improves skin firmness after stress is stopped, the U _R / U _F ratio increasing by 12.4% after 45 days.

The daily use of composition 1 therefore makes it possible to significantly improve the viscoelastic properties of the skin: the skin is firmed while remaining supple and hydrated.

By way of comparison, composition 3 is tested under the same conditions as composition 1, after 15 days and 30 days of treatment.

The experimental results are illustrated in Tables VI, VII and VIII appearing in the appendix to this patent application.

Table VI clearly shows a decrease in the elastic extensibility of the skin throughout the treatment.

Table VII shows that the skin does not become firmer during the treatment and that simply a slowdown in the decrease in the firmness of the skin can be observed.

Table VIII also shows that the skin does not become firmer, the values measured after 15 days and 30 days being very close to each other.

It therefore appears that composition 3, which does not contain an anti-glycation principle, produces only a negligible effect on the elasticity and firmness of the skin, in comparison with the results obtained with composition 1.

c) Anti-wrinkle effect of the compositions of the invention.

The anti-wrinkle effect of composition 2 was studied as follows. 20 volunteers aged 40 to 55 applied composition 2 to the face for four weeks, an untreated crow's feet serving as a control.

Silicone impressions of crow's feet are taken before and after treatment, then observed under a confocal microscope.

The densities of the surface microrelief of the skin (0-54 μm), medium wrinkles (56-110 μm) and deep wrinkles (112-400 μm) are measured on each impression. The results are expressed as a percentage change with respect to tO (before treatment) and with respect to the untreated control zone.

The results (average over 20 subjects) were as follows:

- Increase in microrelief: 6%;

- Reduction of medium wrinkles: 6%;

- Reduction of deep wrinkles: 59%.

The increase in microrelief constitutes a positive result generally indicating an improvement in the level of hydration of the skin.

It goes without saying that the present invention is not limited to the preferred embodiments which have just been described in the foregoing, but on the contrary embraces all variants.

A person skilled in the art will in fact be able to make modifications to the present invention, without going beyond the scope of its characteristic elements, as defined in the claims which follow.

Bibliographic references.

1. Biochem. Biophys. Res. Commun, 48, 1972, p 76-84

2. Biochem. Biophys. Acta, 677, 1981, p 313-317

3. Biochem. Journal, 225, 1985, p 745-752

4. Diabetes and Metabolism, 14, 1988, p 25-30

5. J. Clin. Invest., 91.1993, p 2463-2469

6. Science, 232, 1986, p 1629-1632

7. Biochim. Biophys. Acta, 77, p 1963, 676

8. J. Invest. Dermatol., 99, 1992, p 306-309

9. J. Invest. Dermatol., 91, 1988, p 472-477

Annex.

Annex (continued).

Annex (continuation and end).

Claims

Claims.

1. Cosmetic or dermatological composition, with a view to slowing the aging of the skin and / or increasing the elasticity of the skin, characterized in that it comprises a first active principle chosen from natural or synthetic compounds capable of inhibit the formation of Amadori products by non-enzymatic reaction of sugars, in particular glucose, with the collagen of the skin, said first active principle consisting of a single compound or of a mixture of several compounds; and in that it comprises a second active principle chosen from natural or synthetic compounds capable of inhibiting the activity of skin elastases, said second active principle consisting of a single compound or of a mixture of several compounds .

2. Composition according to claim 1, characterized in that said first active principle is chosen in particular from amino acids, preferably basic, peptides, preferably those containing one or more basic amino acids, allantoin, vitamin E, vitamin B ₁ , vitamin B ₆ , thiourea, dithiothreitol, organic silicon derivatives and / or derivatives of these products.

3. Composition according to claim 2, characterized in that the amino acids include in particular lysine, arginine, histidine.

4. Composition according to claim 2, characterized in that the amino acid derivatives include in particular lysine pyrrolidone carboxylate, arginine pyrrolidone carboxylate, arginine aspartate.

5. Composition according to claim 1, characterized in that said second active principle is chosen from compounds capable of blocking the action of leukocyte elastase and / or elastases synthesized by fibroblasts.

6. Composition according to claim 5, characterized in that said second active principle is chosen in particular from plant extracts rich in tannins, in anthocyanosides, procyanidolic oligomers, soy extract, α-1-anti-trypsin, algae extracts, polysaccharides, in particular sulfated polysaccharides, ceramides.

7. Composition according to any one of claims 1 to

6, characterized in that it further comprises at least one natural or synthetic compound activating the synthesis of collagen, in particular an extract of Centella asiatica, ascorbic acid, peptides, β glucans or extracts of algae or oats containing it or the derivatives of these products.

8. Composition according to any one of claims 1 to

7, characterized in that it additionally comprises at least one natural or synthetic compound capable of inhibiting the production of free radicals, in particular vitamin E or its esters, vitamin C, plant extracts rich in flavonoids or polyphenols, such as Ginkgo biloba, green tea, milk thistle, caffeic acid, ferulic acid, glutathione, enzymes such as superoxide dismutase, glutathione reductase and glutathione peroxidase, zinc salts, mannitol or a derivative of these products.

9. Composition according to any one of claims 1 to

8, characterized in that it further comprises at least one natural or synthetic hydrating compound, in particular polyols, a constituent of NMF such as urea, an amino acid, a honey extract, hyaluronic acid, a mucopolysaccharide, one of the constituents of intercellular cement such as ceramides, fatty acids, cholesterol, phospholipids or a derivative of these products.

10. Composition according to any one of claims 1 to 9, characterized in that it further comprises one or more preservatives, sun filters, excipients, stabilizing agents and / or perfumes.

11. Composition according to any one of claims 1 to 10, characterized in that it comprises from approximately 0.01% to approximately 50% by weight of said first active principle, preferably from approximately 0.1% to approximately 10% by weight, more preferably from about 0.2% to about 5% by weight relative to the total weight of the composition.

12. Composition according to any one of claims 1 to 11, characterized in that it comprises from approximately 0.01% to approximately 50% by weight of said second active principle, preferably from approximately 0.1% to approximately 10% by weight, more preferably from about 0.5% to about 5% by weight relative to the total weight of the composition.

13. Composition according to any one of claims 1 to

12, characterized in that it comprises from approximately 0.01% to approximately 10% by weight, preferably from approximately 0.05% to approximately 5% by weight of compound activating the synthesis of collagen relative to the weight total of the composition.

14. Composition according to any one of claims 1 to

13, characterized in that it comprises from approximately 0.01% to approximately 20% by weight, preferably from approximately 0.1% to approximately 5% by weight of the compound inhibiting the production of free radicals relative to the weight total of the composition.

15. Composition according to any one of claims 1 to

14, characterized in that it comprises from approximately 0.1% to approximately 30% by weight, preferably from approximately 0.5% to approximately 10% of hydrating compound relative to the total weight of the composition.

16. Composition according to any one of claims 1 to

15, characterized in that it comprises in percentage by weight relative to the total weight of the composition:

- from about 0.1% to about 10% of lysine pyrrolidone carboxylate;

- from about 0.1% to about 5% of a soy extract having anti-elastase activity;

17. Composition according to any one of claims 1 to 15, characterized in that it comprises in percentage by weight relative to the total weight of the composition:

- from about 0.1% to about 10% of arginine aspartate; - from approximately 0.01% to approximately 2% of procyanidolic oligomers.

18. Composition according to any one of claims 1 to 15, characterized in that it comprises in percentage by weight relative to the total weight of the composition:

- from about 0.1% to about 5% of L-histidine;

- from about 0.1% to about 5% of a soy extract with anti-elastase activity;

- from about 0.1% to about 5% of an algae extract with anti-elastase effect.

19. Composition according to any one of claims 1 to

- from about 0.1% to about 5% of L-lysine pyrrolidone carboxylate;

- from about 0.1% to about 5% of arginine aspartate;

- from about 0.1% to about 10% of a soy extract with anti-elastase effect.

20. Use of one or more natural or synthetic compounds capable of inhibiting the formation of Amadori products by non-enzymatic reaction of sugars, in particular glucose, with the collagen of the skin and of one or more natural or synthetic compounds capable of inhibiting the activity of skin elastases, as active principles for the preparation of a cosmetic composition intended to combat aging of the skin and / or to increase the elasticity of the skin.

21. Use according to claim 20, in which said compounds are as defined in any one of claims 1 to 10.