FR2734478A1 - Cosmetic and pharmaceutical compsn. with anti-radical and Uv filtering properties - Google Patents

Abstract

Cosmetic and pharmaceutical compsn. for topical or oral admin. comprises a protecting agent with anti-radical and UV filtering properties comprising in a carrier: (i) at least one monomer and/or oligomer of a catechin-type phenol of plant origin; and (ii) at least one hydroxycinnamic acid of plant origin. The extract is prepd. by extracting with warm water, precipitating tannins from the aq. phase by addn. of an inorganic salt pref. sodium chloride and filtering, treating the filtrate with EtOAc, concentrating the organic phase under reduced pressure, adding distilled water, eliminating EtOAc by evapn. under reduced pressure and at not more than 50 deg C, washing the aq. phase with chlorinated polar solvent, eliminating the solvent pref. under reduced pressure evaporation at not more than 50 deg C and drying.

Description

COSMETIC OR PHARMACEUTICAL COMPOSITION
TOPIC OR ORAL USING
ANTI-RADICAL PROPERTIES AND A FILTERING POWER
VIS-A-VIS UV.

 The present invention relates to a cosmetic or pharmaceutical composition that can be used topically or orally and has antiradical properties, in particular against free oxygen radicals, and ultraviolet (UV) filtering power.

 It is known that oxygenated free radicals, involved in many vital processes of the living organism, can have an endogenous origin or an exogenous origin. The endogenous origin is essentially enzymatic: indeed, radical enzymatic reactions are involved in many normal processes such as cellular respiration, prostaglandin synthesis and phagocytosis. These radical active oxygen species can also be initiated by ionizing radiation such as the ultraviolet component of sunlight in our environment.

Although the normal values of these radical entities in any living being are unknown for the moment, we know that their modification is always accompanied by changes in the vital functions in which the entities are involved. These functional changes can manifest themselves in various forms, including: - the oxidative destruction of macromolecules, such as collagen or elastin - the accumulation of metabolically inert intermediates from
for example, oxidative polymerization of unsaturated lipids; - alteration of the membrane structures of certain elements of the
such as mitochondria and lysosomes, following the
lipid peroxidation.

These dysfunctions of normal oxidative processes are implicated in certain diseases such as cancer, atherosclerosis, hypertension, cellular aging which causes, in particular, the formation of wrinkles.

 Nature has provided an endogenous system of defense against radical aggressions under purely enzymatic control, notably thanks to superoxide dismutase (SOD) and glutathione peroxidase. However, in some cases, these defenses may be overwhelmed and require an external reinforcement that can act either as a stimulator of the endogenous system or as an antioxidant trapping free radicals.

 Solar light, an environmental factor to which everyone is exposed, is responsible for certain bodily injuries such as burns, inflammation and skin cancer, one cause of which is the presence of oxygen-free radicals induced by the ultraviolet component of the skin. solar light. The most harmful radiation corresponds to the region between 280 and 400 nm, which cosmetologists designate as zone of UVB and UVA. In general, cosmetic preparations for protecting against these UV rays currently contain, as protective agents, essentially synthetic organic products often associated with mineral products such as zinc oxide or titanium oxide. micronized; the protection offered is only due to a filter effect by absorption of UV radiation. It is therefore an immediate effect and the product must be applied immediately before aggression. In addition, these synthetic products generally have very narrow absorption spectra with maxima located either in the UVB region or in the UVA region.

It would therefore be desirable to be able to use a protective agent that makes it possible to protect against UV aggressions by combined effect of antiradical properties and filtering properties, having a very broad absorption spectrum covering the zone comprised between 270 and 360 nm and comprising two maxima. located one, in the area of
UVB around 290 nm and the other in the UVA region around 330 nm. By the filter effect, the protective agent would thus provide a good immediate protection against both UVA and UVB. Its antiradical properties give it, moreover, a preventive and curative effect obtained either by trapping the free radicals or by stimulating the endogenous defenses of the organism. Such a product could therefore be used before, during, or after exposure to UV rays.

According to the present invention, it has been found that the desired result can be achieved by using a protective agent containing both
1) catechol-type phenolic monomers and / or oligomers derived from plant extracts,
2) hydroxycinnamic acids from plant extracts.

 This protective agent can be used both preventive and curative. It has the advantage of being entirely of plant origin and being soluble in water.

 In a known manner, catechin-type phenolic monomers or oligomers have a good absorption of ultraviolet rays with maxima in the zone of 280 nm, corresponding to UVB, but above all effectively trap oxygen free radicals; this antiradical activity results either from stimulation of the endogenous cellular defenses or from inhibition of lipid peroxidation. Hydroxycinnamic acids offer good uptake of UV with maxima in the 310 to 330 nm region corresponding to UVA but low or no antiradical properties. According to the present invention, it has been found that the combination of the phenolic monomers and / or oligomers and the hydroxycinnamic acids has a synergistic effect with regard to the antiradical properties, as shown in the examples given hereinafter.

The subject of the present invention is therefore a cosmetic or pharmaceutical composition which can be used topically or orally and which contains, in a suitable support, a protective agent having antiradical properties and ultraviolet filtering power, characterized in that the protective agent comprises
1) at least one catechin-type phenol monomer and / or oligomer of plant origin, and
2) at least one hydroxycinnamic acid of plant origin.

 Catechol-type phenol monomers and / or oligomers constitute a fraction of catechin tannins contained in different plant sources, among which mention may be made of green tea, various plant sources, among which mention may be made of green tea, potentilla roots, Grape seeds and pine bark and can therefore be extracted from these plants.

Extracts containing said monomers and / or catechin-type phenol oligomers can be prepared from these plants by methods described in the following published patents.
FR-A-1,427,100, FR-A-2 092 743, FR-A-2 372 823, FR-A-2 643 073,
US Pat. No. 4,698,360 and EP-A-348,741. The method described in French Patent Application No. 94 08615, filed on July 12, 1994 by the applicant, is preferably used. This process is characterized by the following steps: following
a) the plant is extracted with hot water,
b) the tannins of the aqueous phase obtained are precipitated by the addition of a mineral salt, in particular sodium chloride, and the tannins are filtered,
c) the salt filtrate obtained is treated with ethyl acetate,
d) the organic phase obtained is concentrated under reduced pressure;
e) distilled water is added,
f) the ethyl acetate is removed by evaporation under reduced pressure at a temperature not exceeding, preferably, 50.degree.
g) the aqueous phase obtained is washed at least once with a chlorinated polar solvent, in particular chloroform or methylene chloride,
h) removing the residual chlorinated polar solvent from the washed aqueous phase, in particular by evaporation under reduced pressure at a temperature not exceeding about 50 ° C., and
i) the aqueous concentrate obtained is dried to obtain an extract.

In the case where green tea is extracted by the process described above, a relatively high purity extract consisting of about 75% of catechin-type phenol monomers can be obtained in the proportions by weight indicated in the table below.

<tb> (+) - catechin <SEP> 3% <SEP>
<tb> (-) - epicatechin <SEP> 7% <SEP>
<tb> (-) - epicatechin-3-0-gal <SEP> Loyalty <SEP> 7 <SEP>%
<tb> (+ <SEP>) -gallocatechin <SEP> 13 <SEP>%
<tb> (-) - epigallocatechin <SEP> 17 <SEP>%
<tb>(<SEP> + <SEP>) -gallocatechin-3-0-galloylate <SEP> 27 <SEP>%
<Tb>
The remainder consists essentially of oligomers of the above compounds.

 When extracted by the process described above grape seeds or pine bark, the extract contains mostly oligomers and a lower proportion of monomers, this small proportion can be controlled.

 According to the invention, the extracts of green tea, pine bark or grape seed obtained by the process described in the French patent application 94 08615 are preferably used.

 Among the hydroxycinnamic acids, mention may be made of p-coumaric acid, ferulic acid, caffeic acid, sinapic acid and also chlorogenic acids such as 3-caffeylquinic acid and 4-caffeylquinic acid. 5-caffeylquinic acid, 3,4-caffeylquinic acid, 3,5-dicaféylquinic acid, 4,5-dicaféylquinine acid, 4-feruloylquinic acid and 5-feruloylquinic acid.

 These various hydroxycinamic acids, more particularly mixtures of these acids, can be obtained at a higher or lower degree of purity by extraction of different plants, such as certain dicotyledonous plants. According to the invention, use is preferably made of a green coffee extract, more particularly that containing more than 90% by weight of chlorogenic acids, generally about 95%, the preparation of which is described in the French patent application filed on same day by the Applicant under the title "Preparation of a plant extract having total screen properties vis-a-vis UV, plant extract obtained, its use and cosmetic or pharmaceutical composition containing said extract".

According to this process, dried green coffee beans are milled with a fat and caffeine solvent, for example chloroform or methylene chloride; the ground product is extracted for example with an aqueous polar solvent of chlorogenic acids, in particular aqueous methanol, more particularly in a volume proportion of 7/3; the polar solvent is evaporated under reduced pressure at a temperature not exceeding 50 ° C. The remaining aqueous phase is exhaustively extracted with a solvent of the chlorogenic acids that is immiscible with water, in particular ethyl acetate; under reduced pressure the organic phase obtained at a temperature not exceeding 50 ° C; The residue is taken up in distilled water and dried to obtain the dry extract. According to the invention, the green coffee extract obtained by the process described above is preferably used as a source of hydroxycinnamic acids.

 According to the present invention, the hydroxycinnamic acid (s) and the catechol type phenol monomer (s) and / or oligomer (s) are used in the form of a crude extract, in the form of mixture of crude extracts of different origins or in purified form obtained from one or more crude extract (s). Since these products are water-soluble, they can be used in the form of an aqueous solution.

 In order to obtain a homogeneous mixture of the extracts or products used, all the constituents are preferably dissolved in water and then the mixture is dried, for example by nebulization or freeze-drying. However, any known mixing method can be used.

 In the mixture constituting the protective agent, the proportion by weight of the innamidic hydroxycompound (s) relative to the catechol-type phenol monomer (s) and / or oligomer (s) is preferably between 1/9 and 4, but could be higher or lower.

 In cosmetic or pharmaceutical compositions, the protective agent according to the invention is present in an amount sufficient for there to be a filter effect and an antiradical effect. The amounts used are generally between 0.01 and 50% by weight relative to the total weight of the composition.

 The example given below, purely illustrative and non-limiting, will better understand the invention.

EXAMPLE
A) Preparation of extracts
I) Preparation of a green coffee extract
1 kg of dry commercial green coffee is crushed. The powder obtained is treated with 5 liters of chloroform with stirring for 1 hour. The operation is repeated once more so as to obtain a delipidated and decaffeinated product. The delipidated product was extracted with 5 liters of a methanol / water mixture in a volume ratio of 7/3. The organic phase obtained is then concentrated under a reduced pressure of 10 mbar at a temperature not exceeding 500C until complete elimination of methanol. About 1 liter of aqueous phase remains, which is extracted with an equivalent amount of ethyl acetate (1 liter). The organic phase obtained is evaporated to dryness under a reduced pressure of approximately 10 mbar, at a temperature of 40 ° C to give a residue The residue is taken up in 400 ml of distilled water and dried by lyophilization.

 An extract containing 94.5% by weight of chlorogenic acids, of which 50% by weight of 5-caffeylquinic acid is obtained.

2) Preparation of a green tea extract
1 kg of green tea is placed in a flask and 8 liters of hot water are added at 80 ° C. and allowed to stir for extraction for 60 minutes with gentle stirring while maintaining the temperature.

We filter; 3 kg of sodium chloride are added to the resulting solution to precipitate the tannins and filter the tannins. The salted filtrate is treated with 6 liters of ethyl acetate. The organic phase is concentrated at 50 ° C. under a reduced pressure of 10 mbar When 300 ml of concentrate are added, 1 liter of distilled water is added, the ethyl acetate is evaporated off at 50 ° C. under a reduced pressure of 10 mbar.

800 ml of an aqueous phase are obtained which are washed with 300 ml of chloroform. The chloroform is then removed at a temperature of 40 ° C. under a reduced pressure of 10 mbar Finally, the residue obtained is nebulized to obtain a dry extract.

This extract consists of about 75% by weight of the following monomers in the weight proportions indicated below

<tb> (+) - catechin <SEP> 3% <SEP>
<tb> (-) - epicatechin <SEP> 7% <SEP>
<tb> (-) - epicatechin-3-0-galloylate <SEP> 7 <SEP>% <SEP>
<tb> (+) - gallocatechin <SEP> 13 <SEP>%
<tb> (-) - epigallocatechin <SEP> 17 <SEP>%
<tb>(<SEP> + <SEP>) -gallocatechin-3-0-galloylate <SEP> 27 <SEP>%
<Tb>
The remaining percentage consists essentially of oligomers of these monomers.

3) Preparation of a grape seed extract
1 kg of grape seed is placed in a flask and 8 liters of hot water are added at 80 ° C. and allowed to boil for extraction for 60 minutes with gentle stirring while maintaining the temperature.

We filter; 3 kg of sodium chloride are added to the resulting solution to precipitate the tannins and filter the tannins. The salted filtrate is treated with 6 liters of ethyl acetate. The organic phase is concentrated at 500 ° C. under a reduced pressure of 10 mbar. When 300 ml of concentrate is obtained, 1 liter of distilled water is added. Ethyl acetate is removed by evaporation at 50 ° C under a reduced pressure of 10 mbar.

800 ml of an aqueous phase are obtained which are washed with 300 ml of chloroform. The chloroform is then removed at a temperature of 40 ° C. under a reduced pressure of 10 mbar Finally, the residue obtained is nebulized to obtain a dry extract.

4) Preparation of a mixture of green coffee extracts and green tea
Equal weights of the green coffee extract and the green tea extract prepared above were dissolved in distilled water and spray-dried.

5) Preparation of a mixture of green coffee extracts and grape seed extracts
Equal weights of green coffee extract and grape seed extract were mixed as in 4) above.

B) Study of the filtering power
a) Absorption spectrum
Extracts and mixtures of extracts prepared in A) were prepared with 0.1 mg / ml solutions in water and the asterption spectrum and the transmission were measured in a HITACHI U-2000 type apparatus. .

1) Green coffee extract has an absorption spectrum that covers
an area between 270 to 360 nm with a maximum at 323 nm
and a shoulder at 281 nm. The solution allows only one
transmission less than 10% for wavelengths included
between 270 and 350 nm.

2) Green tea extract has an absorption spectrum that covers
an area between 270 and 290 nm with a maximum around
280 nm. The solution allows only a transmission lower than
10% for wavelengths between 270 and 290 nm.

3) Grape seed extract has an absorption spectrum between
270 and 290 nm with a maximum at about 280 nm. The solution
allows a transmission of less than 10% for lengths
between 270 and 290 nm.

4) The mixture weight for weight of green coffee extract and extract of
green tea has an absorption spectrum between 270 nm and 360 nm
with two distinct maxima respectively at 285 and 325 nm. The
transmission is less than 10% for wavelengths
between 270 and 350 nm.

5) The mixture weight for weight of green coffee extract and extract of
Grape seed has an absorption spectrum covering the area
between 270 and 360 nm with two respective maxima at 285 and 325 nm.

Transmission is less than 10% for wavelengths
between 270 and 350 nm.

b) Sun protection factor (SPC)
The protection afforded by the various extracts or mixture of extracts has been estimated in vitro according to the technique described by DIFFEY and ROBSON (J. Soc Cosmet 40 127-133, 1989).

The protective formula studied was prepared from mixtures A and B having the following formulation
Mixture A
Vaseline officinale 2 g
Stearic acid 3 g
Stearic alcohol 2 g
Propyl paraben 0.015 g
Mix B
Distilled water 70.410 g
Extract or mixture of extracts 10 g
Propylene glycol 12 g
Sodium lauryl sulphate 0.5 g
Disodium salt of ethylene acid
diamine tetracetic
(Disodium EDTA) 0.05 g
Methyl paraben 0.025 g
Mixtures A and B are heated separately at 80 ° C with stirring until clear liquids are obtained Mixture A is then added slowly to Mixture B with stirring, stirring is continued until the resulting gel is obtained. at room temperature (20 ° C).

 The preparation obtained contains 10% by weight of extract or mixture of extracts; it is applied in vitro on a non-delipidated human stratum corneum.

The following values of in vitro CPS were obtained for the mixtures of extracts 4 and 5 4 - Green coffee extracts + green tea .. .. .. 33.7 + 6.8 5 - Green coffee extracts + pips of grape. . 18.5 + 4.8
These tests show that the protective agents containing hydroxycinnamic acids and catechol type monomers and / or oligomers of phenol are total screen type filters.

c) Study of the free radical potential of extracts or mixture of extracts
The antiradical potential for free radicals generated by UV was investigated on human fibroblasts grown from skin foreskin neonates or mammoplasties.

In order to overcome the protection by filter effect already highlighted, the extract or mixture of extracts was introduced into the medium
before and after UV irradiation (preventive and curative effect). Solutions in water of 0.1 mg / ml or 10 micrograms per ml have been
applied and the UVB dose used was 290 mJ / cm2.

The following protective activities were obtained

<tb><SEP> 100 <SEP> yg / ml <SEP> 10 <SEP> Imi <SEP>
<tb> Extract <SEP> of <SEP> coffee <SEP> green <SEP> O <SEP>% <SEP> 17 <SEP>%
<tb> Extract <SEP> of <SEP> tea <SEP> green <SEP> - <SEP> 14 <SEP>%
<tb> Extract <SEP> from <SEP> seeds <SEP> from <SEP> grape <SEP> 32 <SEP>% <SEP>
<tb> Extracts <SEP> of <SEP> coffee <SEP> green <SEP> + <SEP> tea <SEP> green <SEP> - <SEP> 40 <SEP>%
<tb> Extracts <SEP> of <SEP> coffee <SEP> green <SEP> + <SEP> seeds <SEP> of <SEP> grapes <SEP> 50 <SEP>% <SEP>
These results show that when using, according to the invention, a mixture of an extract containing hydroxycinnamic acids and an extract containing catechol-type phenol monomers and / or oligomers, there is a synergy with regard to the antiradical potential.

Claims (11)

 1 - A cosmetic or pharmaceutical composition that can be used topically or orally and contains, in a suitable support, a protective agent having antiradical properties and an ultraviolet filtering power, characterized in that the protective agent includes  1) at least one catechol-type phenol monomer and / or oligomer of plant origin, and  2) at least one hydroxycinnamic acid of plant origin.  2 - Composition according to Claim 1, characterized in that the catechol-type phenol monomer (s) and / or oligomer (s) are (are) extracted from green tea, from potentilla roots, grape seeds or pine bark.  3 - Composition according to Claim 2, characterized in that the monomer (s) and / or the catechol-type phenol oligomer (s) are (are) extracted by a process comprising the following steps  a) the plant is extracted with hot water,  b) the tannins of the aqueous phase obtained are precipitated by the addition of a mineral salt, in particular sodium chloride, and the tannins are filtered,  c) the salt filtrate obtained is treated with ethyl acetate,  d) the organic phase obtained is concentrated under reduced pressure;  e) distilled water is added,  f) the ethyl acetate is removed by evaporation under reduced pressure at a temperature not exceeding about 50 ° C.,  g) washing at least once the aqueous phase obtained with a chlorinated polar solvent,  h) removing the residual chlorinated polar solvent from the washed aqueous phase, in particular by evaporation under reduced pressure at a temperature not exceeding about 50 ° C., and  i) the aqueous concentrate obtained is dried to obtain an extract.  4 - Composition according to one of claims 2 or 3, the (s) manomere (s) and / or oligomer (s) of catechetical type is (are) extracted (s) green tea, characterized in that the green tea extract consists of about 75% by weight of catechin-type phenol monomers in the following proportions by weight

the remainder essentially consisting of catechol-type phenol oligomers. <tb> (+) - Gallocatechin-3-0-Galloylate <SEP> 27 <SEP>% <tb> (-) - epigallocatechin <SEP> 17 <SEP>% <tb> (+) - gallocatechin <SEP> 13 <SEP>% <tb> (-) - ep <SEP> icatech <SEP> ine-3-O-galloylate <SEP> 7 <SEP>% <tb> (-) - epicatechin <SEP> 7% <tb> (+) - catechin <SEP> 3%  5 - Composition according to one of claims 1 to 4, characterized in that the (s) hydroxycinnamic acid (s) is (are) chosen from the group formed by p-coumaric acid, ferulic acid, sinapic acid and chlorogenic acids.  6-Composition according to one of claims 1 to 5, characterized in that the (s) hydroxycinnamic acid (s) is (are) extracted (s) green coffee.  7 - Composition according to claim 6, characterized in that the green coffee extract contains more than 90% of chlorogenic acids.  8 - Composition according to one of claims 6 or 7, characterized in that the green coffee extract is obtained by a method according to which treated green coffee beans milled using a grease solvent and caffeine, the product obtained is extracted with an aqueous polar solvent chlorogenic acids, the polar solvent is evaporated under reduced pressure at a temperature not exceeding 50 C, the remaining aqueous phase is depleted by a solvent of non-chlorogenic acids miscible with water, concentrated under reduced pressure the organic phase obtained at a temperature not exceeding 50 ° C, the residue is taken up in distilled water and dried to obtain the dry extract.  9 - Composition according to one of claims 1 to 8, characterized in that the (s) hydroxycinnamic acid (s) and the monomer (s) and / or oligomer (s) phenol type Catechism are in the form of an aqueous solution.  10 - Composition according to one of claims 1 to 9, characterized in that in the mixture constituting the protective agent, the weight proportion of the (s) hydroxycinnamic acid (s) relative to the (x) monomer ( s) and / or catechol type phenol oligomer (s) is between 1/9 and 4.  11-Composition according to one of claims 1 to 10, characterized in that it contains between 0.01 and 50% by weight of protective agent relative to the total weight of the composition.