FR2746008A1 - Compositions containing vitamin C and protease inhibitor - Google Patents

Abstract

Compositions comprising (a) at least one vitamin C derivative, and (b) a protease inhibitor selected from rutin, mulberry leaf concentrate and/or vitamin E acetate, are new.

Description

 The present invention relates to a composition for topical application for preventing or treating skin aging.

 The applicant has developed a composition that simultaneously increases the production of collagen while protecting it from the destructive action of dermal proteases and various free radicals.

A composition according to the invention comprises in combination at least one vitamin C derivative and at least one protease inhibiting agent chosen from rutin, a concentrate of mulberry leaves,
Vitamin E acetate, and mixtures thereof.

 Preferably, the vitamin C derivative contains silicon, and consists of monomethylsilanetriol ascorbate. In a preferred composition, another vitamin C derivative such as ascorbyl palmitate is associated with the silicon-containing derivative.

 A composition according to the invention advantageously comprises a lipoamino acid derived from an amino acid and a fatty acid; a preferred lipoamino acid is hydroxyproline dipalmitate.

The most appropriate proportions of each of the constituents of the composition defined above are the following, these proportions being expressed in percentage by weight relative to the weight of the composition.
- derivative (s) of vitamin C: 2.0 to 10.5%
protease inhibiting agent: 0.7 to 4%
lipoamino acid: 1 and 5%
When the composition comprises a vitamin C derivative which contains silicon, the proportion of the latter is preferably between 2 and 10% by weight relative to the weight of the composition.

A composition of the invention makes it possible, through the action of its combined components, to create a balance between the process of destruction or catabolism, and the process of tissue reconstruction or anabolism, by obtaining the following effects
* increased synthesis of connective macromolecules, in particular collagen,
* Protection of collagen and elastin networks against the destructive action of endogenous proteases, in particular with respect to collagenase and elastase,
inhibition of the glycation phenomena which lead to the formation of unscheduled bonds between the collagen molecules resulting in a loss of their functional properties,
* neutralization of free radicals.

 Another subject of the invention is a cosmetic preparation comprising a composition as defined above.

 The choice of active ingredients made according to the invention also makes it possible to obtain stable cosmetic compositions and preparations, in particular with regard to oxidation.

The objects of the invention are now described in more detail and their properties illustrated in the following Examples 1 to 4 and Figures 1 to 4 which are rat skin cutting photographs and according to which
Figure 1 corresponds to untreated skin and before enzymatic action of collagenase,
Figure 2 corresponds to untreated skin and after enzymatic action of collagenase,
FIG. 3 corresponds to a skin treated with the M3 composition of the invention, and before the enzymatic action of collagenase,
FIG. 4 corresponds to a skin treated with the M3 composition of the invention, and after enzymatic action of collagenase,
EXAMPLE 1 In Vitro Comparison of the Anti-Protease Effect on Elastase, a Composition of the Invention and Known Cosmetic Compositions
Only the associations of water-soluble compounds could be studied in vitro.

 3 compositions that have been shown to be very effective in inhibiting elastase activity in vitro, are compared and the results are summarized in the table below.

M10 is a composition which is the subject of the French patent application published under No. 2,594,690, and which is marketed under the trademark Derm Repaire by ESTHEDERM
M8bis is an active ingredient consisting of a hydrolyzate of marine proteins of the Aosa alga, used in so-called "anti-aging" compositions and marketed by SECMA under the trademark AosaïneB; and
M3 is a composition of the invention.

TABLE 1

<tb><SEP> Compositions <SEP>% <SEP> final <SEP> in <SEP> Inhibition
<tb><SEP> buffer <SEP> in <SEP>%
<tb><SEP> M10 <SEP> 5% <SEP> 15% <SEP>
<tb><SEP> M8bis <SEP> 5 <SEP>% <SEP> 10 <SEP>% <SEP>
<tb><SEP> M3:
<tb><SEP> Ascorbosilane <SEP> C <SEP> 4 <SEP>%
<tb><SEP> + <SEP> Rutin <SEP> 0.1 <SEP>% <SEP> 12 <SEP>%
<tb> + <SEP> Conc.Feuil.Mûrier <SEP> 1 <SEP>%
<Tb>
EXAMPLE 2 Inhibition of In Vitro Collagenase of a Composition of the Invention
The same 3 preparations of Example 1 exerted an inhibitory action on the activity of collagenase in vitro.

It emerges from Examples 1 and 2 that
The Derm Repaire combination, the most effective in the inhibition of elastase in vitro, is also of interest in the inhibition of collagenase in vitro,
the composition M3 comprising a combination of ascorbosilane C, rutin and a concentrate of mulberry leaf develops in vitro an anti-elastase and anti-collagenase activity of first order,
- Aosain develops an in vitro anti-elastase and anticollagenase activity of less importance.

EXAMPLE 3 In Vitro Comparison of the Protection of the Elastin and Collagen Substrates by a Composition of the Invention and by Known Cosmetic Compositions
Only Aosain8 has a protective activity against the enzymatic degradation of elastin. But this effect is not found in vivo.

 4 compositions exert a collagen protective activity against collagenase degradation. The comparative results are presented in the following Table 2.

TABLE 2 * Esculosaponin 1% 40% inhibition * Ascorbosilane C + rutin + conc. sheet. mulberry 27% inhibition * "AE" complex at 5% 25% inhibition
(anti-elastase complex marketed by SOLABIA) * Derm Repaire 17% inhibition
+ Escine at 1%
EXAMPLE 4 In Vivo Studies
a) In vivo anti-elastase effect of a composition of the invention
The anti-elastase effect of the compositions M10 (Derm Repaire) and M8bis (AosaïneB) of Example 1 is not found in vivo.

 The anti-elastase effect of the composition M3 according to the invention and described in Example 1 is observed in vivo.

b) In vivo anti-collagenase effect of a composition of the invention
The inhibitory action of the collagenase activity is found in vivo only for the composition M3 corresponding to the combination of ascorbosilane C, rutin, and concentrate of mulberry leaves as illustrated in FIGS. 4.

 According to FIG. 1, which is a photograph of a section of the skin of a rat not treated with the M3 composition of the invention and before the action of collagenase, dense and normally arranged collagen bundles are clearly distinguished.

 According to FIG. 2 which is a photograph of a section of the skin of a rat not treated with the M3 composition of the invention and after the action of collagenase, the collagen bundles appear faded, with fuzzy outlines, less dense and in a much smaller proportion.

 According to FIG. 3, which is a photograph of a section of the skin of a rat treated with the M3 composition of the invention and before the action of collagenase, there are well-dense and normally structured collagen bundles comparable to those of Figure 1.

 According to FIG. 4 which is a photograph of a section of the skin of a rat treated with the M3 composition of the invention and after the action of collagenase, the collagen is seen to be fairly dense, covering a large part of the surface. of the cup. In the middle dermis the bundles are a little fuzzy, but as a whole, the collagen is much less degraded than that shown in Figure 2.

c) Protective effect of elastin and collagen in vivo
The protective effect of Aosaïne8 observed in vitro is not found in vivo.

In addition, among the four compositions mentioned in
Table 2 above, only the protective activity of the ascorbosilane mixture
C, rutin and mulberry leaf concentrate is stored in vivo.

d) In vivo morphological studies
Before the action of collagenase, only 3% AUC, a collagen III synthesis stimulation agent marketed by Merck, seems to stimulate the biosynthesis of collagen, the difference with respect to the untreated batches being nevertheless only slightly superior. at 1%. It is therefore necessary to relativize the scope of this result, considering also that in 3 out of 4 cases, the excipient alone has also proved effective.

After the action of collagenase, a protective effect of substrate has been demonstrated for two neighboring mixtures * Composition IVD
Hydroxyproline dipalmitate (DPHP) 2%
Ascorbyl palmitate 1%
0.2% vitamin E acetate
Ascorbosilane C 4%
Rutin 0.1%
Conc. sheet. mulberry 1%
Escine 1% * Composition VIG
It has the same composition as the IVD composition, with the exception of the escin that it does not contain.

DPHP blend, ascorbyl palmitate, vitamin acetate
E, ascorbosilane C, rutin, mulberry leaf concentrate, is the only one to exert an inhibitory action of endogenous proteases both in vitro and in vivo.

 This composition is therefore of major interest for the development of a range of products intended to prevent and treat aging of the skin.

 EXAMPLE 5 An effective preparation in the prevention and treatment of aging of the skin preferably responds to the following formulation.

Anti-protease and anti-radical constituents
Rutin 0,1 - 1
Concentrate of mulberry leaves 0,5 - 2
Vitamin E acetate 0.1 - 1
Vitamin C derivatives
Monomethylsilanetriol Ascorbate 2 - 10
Ascorbyl Palmitate 0.5
lipoaminoacid
Hydroxyproline dipalmitate 1 - 5
Components of the excipient
Demineralized water qs 100
Cetearyl heptanoate 8 - 10
Hexadecyl potassium phosphate 3
Beeswax 3-5
Polymers of Acrylic Acid 0.7 - 1
Triethanolamine 1.15
Butyl hydroxy toluene 0.05
Disodium EDTA 0.2
Iron oxides 0.004 - 0.008
conservatives
Parabens, Phenoxyethanol 0.55

Claims (12)

 A composition comprising in combination at least one vitamin C derivative and at least one protease inhibiting agent selected from rutin, a mulberry leaf concentrate, vitamin acetate E, and mixtures thereof.  2. Composition according to claim 1, characterized in that the protease inhibiting agent consists of a mixture of rutin, mulberry leaf concentrate, and vitamin E acetate.  3. Composition according to claim 1 or 2, characterized in that the vitamin C derivative contains silicon.  4. Composition according to claim 3, characterized in that the vitamin C derivative containing silicon is monomethylsilanetrio ascorbate.  5. Composition according to claim 3 or 4, characterized in that it contains another vitamin C derivative which is ascorbyl palmitate.  6. Composition according to any one of the preceding claims, characterized in that it further contains a lipoamino acid derived from an amino acid and a fatty acid.  7. Composition according to claim 6, characterized in that the lipoamino acid is hydroxyproline dipalmitate.  8. Composition according to any one of the preceding claims, characterized in that the proportion of the vitamin C derivative is between 2.0 and 10.5% by weight relative to the weight of the composition.  9. Composition according to claims 3 or 4 and 8, characterized in that the proportion of the vitamin C derivative containing silicon is between 2 and 10% by weight relative to the weight of the composition.  10. Composition according to any one of the preceding claims, characterized in that the proportion of the protease inhibiting agent is between 0.7 and 4% by weight relative to the weight of the composition.  11. The composition of claim 6 or 7, characterized in that the proportion of lipoamino acid is between 1 and 5% by weight relative to the weight of the composition.  12. Cosmetic preparation comprising a composition according to any one of the preceding claims.