WO1997028814A1 - Use of uva ursi and/or lespedeza capitata plant extracts and cosmetic and pharmaceutical compositions containing same - Google Patents

Abstract

The use of Uva Ursi and/or Lespedeza Capitata plant extracts, and cosmetic and pharmaceutical compositions containing same, are disclosed. The use of an Uva Ursi plant extract and/or a Lespedeza Capitata plant extract as the active ingredient in a topical cosmetic and/or pharmaceutical composition for the skin, said extracts advantageously being present in a fraction by weight of 0.0001-5 %, is also disclosed.

Description

 Use of extracts of the Uva Ursi plant and / or of the Lespedeza Capitata plant and cosmetic and pharmaceutical compositions comprising such extracts

The present invention relates to the field of cosmetology, in particular skin care, and relates to the use for cosmetic or pharmaceutical applications of an extract of the Uva Ursi plant and / or of an extract of the Lespedeza plant. Capitata and a corresponding cosmetic and / or pharmaceutical composition.

The reaction of reducing sugars (glucose or xylose) with proteins during the sterilization of food was observed as early as 1912 by L. MAILLARD (CR Acad. Se 1912, 154: 68-68) in the form of a browning reaction . In 1981 (Science, 1981, 21 1, 491-493), A. CERAMI described protein glycation or non-enzymatic glycosylation in opposition to enzymatic glycosylation by glycosyltranferase. He mentioned the possible role of this glycation in the aging of tissues.

The biochemical mechanism of this reaction is well known and has two phases:

- an early phase: reaction of reducing sugars (glucose, fructose) with the terminal or lateral amino functions of tissue constitutive proteins to produce compounds called "Schiff Bases". These compounds are then stabilized by rearrangement of Amadoπ into cetoamine. - a late phase: the cetoamine functions are oxidized to deoxyosone in the presence of oxygen and react with other basic amino acids such as arginine or lysine belonging to other proteins (albumin, lipoproteins, immunoglobulin). The result is the formation of complexes with final bridges of the pentosidine or 2 furoyl 6.3 type. furon \ l 1.4 imidazole.

The glycation of proteins causes the formation of inter and intra molecular bridges at the level of proteins with slow renewal, then the browning and the insolubility of these proteins.

Proteins damaged by glycation in the skin are: fibronectme, laminin and especially elastin and the different types of collagen (I and IV). In normal skin, glycated proteins are eliminated metabolically and by cellular digestion by macrophages resulting in reshaping of the dermis.

But this elimination decreases with age, leading to an accumulation of these glycated proteins and an aggravated aging of the dermis by the addition of several phenomena ^• resistance to renewal proteases and reduction of fibrogenesis of collagen and therefore of its renewal, reduction of its filtering activity in the extra-cellular matrix and in particular in the dermo-epidermal junction after fixation of foreign proteins (LDL, cholesterol, albumin) causing its thickening

These various cumulative phenomena lead in particular to the production of oxygenated free radicals, aggravated by UV-A, resulting in degradation of collagen, activation of non-specific harmful proteases, activation of macrophages and secretion of cytokines (TNFa). final implications of the above actions may consist of inflammation of the skin, leading to fibrosis and lipofuscin deposits

The foregoing presentation highlights the advantage of using substances with an anti-glycation effect, in particular in the fight and prevention of skin aging in cosmetics.

Various substances of this nature have already been listed to date.

Thus, substances are known which reduce the level of fixed proteins and inhibit complex bridging such as aminoguadimne, hydrazine (see in particular EP-A-0 322 402) or various basic amino acids, in particular lysine, 1 argimne or histidine (see in particular EP-A-0 222 313)

In addition, hypoglycemia reduces, in known manner, glycation and elimination of glycated proteins can be increased by activation of macrophages under the effect of cytokines, however, these methods are difficult to implement and are outside the scope of the invention. cosmetic application

Furthermore, various substances with anti-glycation activity are already known, including in particular aminoguanidine, the use of the latter being however limited to medical therapy since, in the case of a drug B, it is also known to use different acids amines (His, Lys,

Arg) consisting of constituents of NMF (Lys, Arg) or precursors of urocanic acids (His), these however lacking in effectiveness, originality and specificity in terms of anti-glycation activity

In addition, there is also a silicone derivative having an anti-glycation activity, without however the latter reaching significant values likely to cause visible effects, especially in the short or medium term.

In addition, anti-radical substances, already widely used in cosmetics, are known to protect collagen from damage caused by free radicals. Thus, certain flavonoids, by their ability to fix on collagen, are liable to protect the latter against free radicals (VILJANEN-TARIFA E CR Soc Biol, 187, 263-267, 1993)

Furthermore, it is also known that the leaves of the Uva Ursi plant mainly contain hydroquinone derivatives, such as the following compounds

- arbutoside (hydroqumone-β-O-glucoside 6 or 10% arbutin),

- methylarbutoside,

- galbutic acid esters of arbutin,

- gallic and ellagic tannins (15 to 20%) - flavonoids (quercitπne, isoquercitπne, myπcetine),

- phenol-carboxylic acids,

- pentacychic tπterpenes (ursolic lupeol, amyπne) In pharmacies, extracts of Uva Ursi (leaves) are known and used as astringents, diuretics and antiseptics uπnaires The depigmenting activity of arbutoside and its derivatives is also well known Indeed, 1 arbutoside releases by diprolysis a diphenol s which immediately oxidizes to hydroquinone, a skin depigmenting reference substance

Similarly, it is known that the main chemical compounds present in the extracts of aerial parts of Lespedeza Capitata are flavonoids of tannins and acid-phenols, their relative proportions varying according to the nature of the extracts (See on this subject EP-A- 0 054 486)

Analysis of the latter revealed the presence of a very complex composition of flavonoids, comprising at least 23 heterosides of flavonoids (see in particular LINARD A., DELA VEAU P, PARIS RR medicinal plants and phytotherapy No. 2, 12 1978, p 144-147) Thus, an analysis of extracts of Lespedeza Capitata, carried out by the inventors, made it possible to highlight in particular the following substances:

- luteolin derivatives,

- apigenin derivatives, - chysoeriol derivatives,

- orientin,

- isoorientine,

- di-glycosyl apigenin,

- rutoside, - di-glycosyl luteolin,

- phenolic acids.

In pharmacies, the compounds and / or extracts of Lespedeza Capitata are used for their hypoazotemic, diuretic, hypocholesterolemic properties. Their anti-tumor and anti-viral activities are also known.

The object of the present invention is therefore to provide substances having an intensity of anti-glycation efficacy substantially equivalent or comparable to that of aminoguanidine, while being able to be used both in cosmetics and in pharmacy. In addition, these new anti-glycation substances must be of natural origin, if possible vegetable, non-toxic, easily tolerable and of an acceptable cost price.

However, the inventors of the present invention have found, unexpectedly and surprisingly, that extracts of the plant Uva Ursi and / or of the plant Lespedeza Capitata exhibited, owing to their particular compositions, in particular in flavonoids, an anti - pronounced glycation of protein molecules.

Thus, the main object of the present invention relates to the use of an extract of the Uva Ursi plant and / or of an extract of the Lespedeza Capitata plant as an active agent with anti-glycation action on protein molecules in a cosmetic and / or pharmaceutical composition for topical use for the skin, making it possible to prevent and combat skin aging.

The corresponding dermatological compositions may for example be solid or liquid and may be in the dermatological forms commonly used, such as for example creams, gels, ointments, lotions, skin milks, shampoos and various products rinsed or under form of liposomes. They are prepared according to the usual galenic methods. The compositions of the invention may contain, in addition to extracts of Uva-Ursi and / or Lespedeza, other active compounds having particular skin properties. The cosmetic compositions according to the invention can be in any form used in cosmetology. creams or gels in jars or tubes, milk or lotion in glass or plastic bottle and possibly in dosing bottles, ampoules, aerosols

The invention relates to cosmetic compositions characterized in that they are in the form of a cream, gel, milk, lotion, emulsion, liquid soap, dermatological bread or shampoo.

They are preferably presented in one of the following forms

- aqueous gels, fatty gels, - simple emulsions, water in oil,

- simple emulsions, oil in water,

- multiple emulsions, for example water in oil in water, or oil in water in oil,

- a triple emulsion, water in oil in water, - a triple emulsion, oil in water in oil,

- pseudoemulsions,

- microemulsions, oil in water in oil.

The various cosmetic forms mentioned above can be obtained according to the usual methods used in this field. The present invention relates very particularly to the compositions as defined above, characterized in that their excipients are suitable for application to the face, the neck, the hands and the body.

According to a characteristic of the invention, the extract of the Uva Ursi plant or of the Lespedeza Capitata plant is advantageously obtained from the aerial parts of said plants, namely leaves and / or stems.

As an example of an extraction process from the Uva Ursi plant. i! can be implemented a method consisting in carrying out successively, on the one hand, an extraction on a reflux apparatus using a suitable solvent, in particular a polar solvent such as ethanol, methanol or an aqueous solvent, on the other hand firstly, evaporation of the solvent under vacuum, and finally drying in an oven at 40-50 ° C (process no. 1) As a variant, the extract can also be obtained by using a solvent consisting half of ethanol and water and by successively carrying out a reflux extraction for approximately one hour, with stirring in a flask, then filtration through a standard container. Buchner, then evaporation of the solvent under vacuum and, finally, drying in an oven at 40 ° C - 50 ° C, or by lyophilization or by atomization (process n ° 2).

According to a second alternative embodiment, the extract can be obtained by using methanol as solvent and by successively carrying out the steps consisting of: extraction on a reflux apparatus, filtration of the methanolic extract of green color on a filter activated carbon, rinsing the filter with clean methanol, a mixture of the resulting brown filtrates, evaporation of the solvent in vacuo and drying in an oven at 40-50 ° C (process 3)

According to a third alternative embodiment, the extract can be obtained by using methanol as solvent and by successively carrying out the stages consisting of: extraction in a reactor of 1 kg of powder in 5 liters of solvent (with stirring), a extraction at reflux for 1 hour in the solvent, cooling to ambient temperature, filtration through Buchner, filtration of the methanolic extract (extract 1) of green color on activated carbon filter, rinsing of the filter with methanol, combination of filtrates (extract 2), evaporation of the solvent under vacuum, drying in an oven at 40-50 ° C, extraction of the residue with two new methanol charges and identical treatments of the resulting extracts (process no. 4 )

The conditions for implementing these processes, the raw materials and the solvent used, as well as the extraction yield and the appearance of the extract obtained are summarized, for different embodiments of the invention, in the table. 1 below Table 1

A titre d'exemple de mise en oeuvre d'un procédé d'obtention d'un extrait de la plante Lespedeza Capitata, il peut être prévu, en utilisant comme solvant de l'ethanol à 60 %, de réaliser les étapes successives suivantes, consistant en : une extraction pendant I h à reflux, sous agitation dans un réacteur ; un refroidissement à température ambiante, une filtration sur Buchner, une réextraction du résidu par 10 volumes de solvant (traitement identique), un mélange des deux filtrats, une evaporation du solvant sous vide à 55° C et une lyophilisation de l'extrait concentré.

By way of example of implementation of a process for obtaining an extract of the Lespedeza Capitata plant, provision may be made, using 60% ethanol as solvent, to carry out the following successive steps, consisting of: extraction for 1 h at reflux, with stirring in a reactor; cooling to room temperature, filtration on Buchner, re-extraction of the residue with 10 volumes of solvent (identical treatment), a mixture of the two filtrates, evaporation of the solvent in vacuo at 55 ° C and freeze-drying of the concentrated extract.

According to a second alternative embodiment, a process for obtaining an extract of the Lespedeza Capitata plant, using water as the solvent, can comprise the following successive stages consisting of: extraction for 1 h at 80 ° C., with stirring in a reactor; cooling to room temperature, centrifugation and filtration of the supernatant, reextraction of the residue twice with 10 volumes of solvent (identical treatment), mixing of the supernatants, concentration of the mixture 20 times by evaporation under vacuum at 40 ° C. and lyophilization of the concentrated extracts.

The conditions for carrying out these two processes, the raw materials and the solvents used, as well as the extraction yield are summarized in Table 2 below. Table 2

The anti-glycation activity of Uva Ursi plant extracts (or

Arctostaphylos Uva Ursi Sprengel or Bearberry) from the Ericaceae family or from the Lespedeza Capitata plant has been demonstrated by a biochemical method, by comparison with a reference anti-glycation substance, namely aminoguanidine, by implementing the steps consisting in

- dissolve human collagen I (SIGMA) at 4 mg / ml in acetic acid at 1/1000 (0.02N) (stir overnight at room temperature), - mix the collagen I solution (1 ml) with 1 ml glucose to

4% in water, 1 ml of 0.2 M phosphate buffer pH = 7.4 (with and without 0.2% albumin) and 1 ml of test substance dissolved in water (if the solution has particles, filter to 0.22 μm),

- incubate 21 days at 45 ° C, - mix the suspension by vigorous shaking then centrifuge at 5000 rpm for 30 min,

- recover the supernatant and carry out fluorescence measurements (excitation at 350 nm, emission at 430 nm)

During each test, the results were expressed as a percentage relative to a sample or a control dose with glucose (100% = control with glucose)

After three tests, the mean and the standard deviation were calculated for each dose tested and were used to draw up the graphical representations of Figures 1, 2, 3 and 4 of the accompanying drawings. In these figures, C represents collagen , Am represents aminoguanidine and A represents albumin

Collagen glycation tests in the presence of albumin were performed to assess the role of foreign proteins (elastin, fibronectin, proteoglycans) on the aging process of the dermis (Figures 1A, 2A, 3A and 4A)

The tests, the results of which served as the basis for establishing the comparative parts of the graphic representations of FIGS. 2 and 4 of the annexed drawings, were respectively carried out by means of test doses 8 containing, with various concentrations indicated, an extract of the Uva Ursi plant corresponding to the reference (2) in Table 1 (Uva Ursi *) and an extract of the Lespedeza Capitata plant corresponding to the reference (1) in Table 2 (Lespedeza *)

A comparative study of the graphic representations of FIGS. 2 and 4 compared to the representations of FIG. 1 shows very clearly and obviously the anti-glycation activity of the plant extracts mentioned above. Table 3

référence du produit testé à 0,1 % selon tableau 1

reference of the product tested at 0.1% according to table 1

The comparison of the anti-glycation activity results in Table 3 above demonstrates that the extracts of Uva-Ursi prepared according to various extraction methods summarized in Table 1 (without limiting the extraction method) have a activity equal to or even greater than aminoguanidine (reference substance) and arbutin alone, a component of Uva Ursi extract.

The present invention also relates, on the one hand, to a cosmetic composition or product intended to prevent and combat the effects of skin aging, characterized in that it (it) contains by way of active agent a cosmetically effective amount of extract of Uva Ursi and / or Lespedeza and. on the other hand, a composition or a pharmaceutical product in particular with dermatological application and with anti-glycation effect, characterized in that it (it) contains as active agent a pharmacologically effective amount of extract of Uva Ursi and / or ^extract of Lespedeza Capitata.

Advantageously, the aforementioned compositions can comprise between 0.0001% and 5% by weight of extract of Uva Ursi obtained according to any one of the methods previously described, of extract of Lespedeza Capitata, or of a mixture of these two extracts When the two aforementioned plant extracts (from Uva Ursi and from Lespedeza Capitata) are present simultaneously, in combination, in the aforementioned products or compositions, with a total weight percentage of the two extracts of between 0.0001% and 5.0000% by weight, preferably between 0.01% and 5.00% by weight (relative to the product or the composition), it may have been composed of a synergy of action of the two extracts, greater whose effect is greater than the actions of the two extracts taken separately.

In the presence of a mixture of the two aforementioned extracts in a composition or a product, each of said extracts may constitute between 50% and 90% by weight of the total amount of the mixture of extracts present (the remainder consisting of other of said two extracts).

It was also found that, in addition to 1 anti-glycation action, the abovementioned plant extracts also exhibited anti-free radical, anti-inflammatory and anti-protease properties. These properties reinforce the interest of using extracts of Uva-Ursi and / or Lespedeza Capitata to prevent or to fight against skin aging

The present invention also relates to a cosmetic treatment method for combating aging of the skin, characterized in that a sufficient amount of a cosmetic composition as defined above is applied to the skin.

By way of non-limiting examples of practical embodiments of the invention, the following will be described various cosmetic or dermatological products or preparations, comprising extracts from the plant Uva Ursi and / or from the plant Lespedeza Capitata Example 1

A cosmetic product in the form of a lotion in accordance with the invention may, for example, have a weight composition as indicated below.

- PEG-40 - Hydrogenated Castor Oil 0.600% - Perfume 0.100%

- Glycerin 10.00%

- LS 48 type stabilizer (Serobiological Laboratories) 0.300%

a Ursi (Référence 9 - tableau 1 ) 0,02 %- Extract

a Ursi (Reference 9 - table 1) 0.02%

- Distilled water qs 100% The process for preparing the aforementioned lotion consists in dissolving the stabilizer in water and glycerin at 30 ° C with stirring, then adding the extract of Uva Ursi (with stirring), to add then the PEG-40 - Oil mixture of hydrogenated castor oil + perfume (with stirring) and, finally, to filter the resulting mixture. Example 2:

A cosmetic product in the form of an oily cream in water, with anti-aging action, in accordance with the invention may, for example, have a weight composition as indicated below.

- Cetyl alcohol 5,000%

- Caprylic / Capric Triglyceride 9,000%

- Paraffin oil 6,750% - Glycerol stearate 2,000%

- Dimethicone 0.250%

- Octyl-2-dodecanol 0.500%

- Lipodermol LS (Serobiological Laboratories) 1,500%

- Distilled water 50,000% - Elestab 41 12 (Serobiological Laboratories) 0.400%

- Glycerin 3,500%

- potassium cetyl phosphate 3,000%

- Uva Ursi extract (Reference 2 - table 1) 2,000%

- Lespedeza Capitata extract (Reference 2 - table 2) 0, 100% - Distilled water qs 100

- Sq fragrance

The process for the preparation of the above-mentioned product consists in melting the various components of the fatty phase together (at 80 ° C.), then in preparing the aqueous phase (distilled water + glycerin + Elestab 41 12 + potassium ketyl phosphate) and in stirring at 80 ° C. until complete dissolution, then pour the fatty phase into the aqueous phase and continue stirring while gradually cooling, adding with stirring the two active extracts of Uva Ursi and Lespedeza Capitata, previously dispersed in their weight propylene glycol, and finally continuing agitation ^until the return to ambient temperature. Example 3:

A cosmetic product in the form of a gel with anti-aging action with Uva Ursi liposomes, in accordance with the invention may, for example, have a weight composition as indicated below.

- Distilled water 71, 40% - LS 48 stabilizer (Serobiological Laboratories) 0.27%

- Glycerin 3.20%

- Sodium hyaluronate 0.10% - Xanthan gum 0.35%

- Distilled water 9.65%

- LS 48 stabilizer (Serobiological Laboratories) 0.03%

- Phospholipid liposomes with 1% Uva Ursi extract (Ref 9) 15.00% The process for preparing the above-mentioned gel may consist in first dissolving the stabilizer in distilled water (stirring for one hour at room temperature) , then add the glycerin and adjust the pH value, if necessary, to around 6.5, then introduce the sodium hyaluronate with turbine stirring and the Xanthan gum gel prepared separately, add the liposomes of Uva Ursi and, finally, continue stirring at room temperature until perfect product homogeneity is obtained

Of course, the invention is not limited to the embodiments described. Modifications remain possible, in particular from the point of view of the constitution of the various elements or by substitution of technical equivalents, without however departing from the field of protection of the invention

Claims

1. Use of an extract of the Uva Ursi plant and / or of an extract of the Lespedeza Capitata plant as an active agent with anti-glycation action of protein molecules in a cosmetic and / or pharmaceutical composition for topical use for the skin. 2. Use according to claim 1, characterized in that the plant extract is obtained from the aerial parts of said plants, namely leaves and / or stems. 3. Use according to any one of claims 1 and 2, characterized in that the plant extract is obtained by extraction using a polar solvent, such as ethanol, methanol or an aqueous solvent. 4. Cosmetic composition intended to prevent and combat the effects of skin aging, characterized in that it contains, as active agent, a cosmetically effective amount of extract of Uva Ursi and / or Lespedeza Capitata. 5. Cosmetic composition according to claim 4, characterized in that it comprises between 0.0001% and 5% by weight of extract of Uva Ursi, extract of Lespedeza Capitata, or a mixture of these two extracts. 6. Pharmaceutical composition, in particular for dermatological application and with anti-glycation effect, characterized in that it contains, as active agent, a pharmacologically effective amount of Uva Ursi extract and / or Lespedeza Capitata extract. 7. Pharmaceutical composition according to claim 6, characterized in that it comprises between 0.0001% and 5% by weight of extract of Uva Ursi, of extract of Lespedeza Capitata, or of a mixture of these two extracts . 8. Cosmetic treatment method for fighting against aging of the skin, characterized in that it consists in applying to the skin a sufficient amount of a cosmetic composition according to any one of claims 4 and 5.