WO2009047618A1

WO2009047618A1 - Cosmetic and/or dermatological compositions and use thereof for depigmentation

Info

Publication number: WO2009047618A1
Application number: PCT/IB2008/002657
Authority: WO
Inventors: Florent Yvergnaux; Lucie Couturier
Original assignee: Societe La Biochimie Appliquee Solabia S.A.
Priority date: 2007-10-11
Filing date: 2008-10-07
Publication date: 2009-04-16
Also published as: FR2922102B1; FR2922102A1

Abstract

The invention relates to the field of life needs and more particularly to the field of cosmetics and/or dermatology. The invention more particularly relates to cosmetic and/or dermatological compositions having depigmentation properties, characterised in that they contain as an active ingredient a pseudoceramid having a fatty acid fraction derived from an unsaturated and mainly poly-unsaturated fatty acid. The invention also relates to the use of pseudoceramids of the general formula I as a depigmentation agent.

Description

Cosmetic and / or dermatological compositions and their use for depigmentation

The present invention relates to the field of the necessities of life, and particularly to the cosmetic and / or dermatological fields.

It more particularly relates to cosmetic compositions and / or dermatological depigmenting action whose active ingredient is a pseudoceramide whose fatty part is a monounsaturated fatty acid or poly unsaturated.

It concerns specifically:

1 °) cosmetic and / or dermatological compositions, characterized in that they contain as active ingredient at least one compound corresponding to the formula (Ic):

in combination or mixed with an inert, non-toxic vehicle suitable for topical application.

2 °) cosmetic and / or dermatological compositions characterized in that they contain, as active ingredient, at least one compound corresponding to the formula (Ib):

3 °) cosmetic and / or dermatological compositions characterized in that they contain as active ingredient a mixture formed of the compound of formula la

in the proportion 2/3 and the compound of formula Ic

1/3 in combination or mixed with an inert vehicle, non-toxic, suitable for topical application.

The subject of the invention is also cosmetic and / or dermatological compositions containing, as active ingredient, at least one compound corresponding to formula (I):

in which :

m is an integer selected from values 1 and 2;

n is an integer selected from the values 0, 1 and 2;

X is chosen from hydrogen and a hydrocarbon chain containing from 1 to 4 carbon atoms;

- R1 and R3 are carbon chains, saturated or unsaturated, having from 4 to 25 carbon atoms and optionally 1 to 2 hydroxyl groups borne by separate carbons;

- R2 is chosen from hydrogen and an alkyl chain having from 1 to 4 carbon atoms, linear or branched, and may comprise a hydroxyl group;

R 4 is chosen from the groups -H, -OH, -SH, -COOH and a linear or branched, saturated or unsaturated carbon chain containing from 1 to 22 carbon atoms terminated by a group chosen from -H, -OH; , -SH and -COOH.

The invention also relates to the use of these compositions for depigmenting purposes.

The invention relates specifically to the use, as in formula (I), R1 is an unsaturated fatty acid chain, especially oleic, linoleic, alpha-linolenic, gamma-linolenic, punicic, eicosapentaenoic or docosahexaenoic.

- in which :

m is an integer selected from values 1 and 2;

n is an integer chosen from the values O, 1 and 2;

X is chosen from hydrogen and a hydrocarbon chain containing from 1 to 4 carbon atoms; - R1 and R3 are carbon chains, saturated or unsaturated, having from 4 to 25 carbon atoms and optionally 1 to 2 hydroxyl groups borne by separate carbons.

R 4 is chosen from the groups -H, -OH, -SH, -COOH and a linear or branched, saturated or unsaturated carbon chain containing from 1 to 22 carbon atoms terminated with a group chosen from -H, -OH, -SH and -COOH, for the purpose of producing a depigmenting preparation to be applied to the body surface, as depigmenting agents

The pigmentation of human skin is one of the major areas of research in the skin field. The fields of application are varied and include in particular cosmetics and dermopharmacy.

Depending on the desired applications it may be interesting to increase or limit the production of melanin, which is the main cause of skin pigmentation.

For the depigmentation it is possible to act at different levels, from the stages prior to the production of melanin until the destruction of the melanin produced (Pigment CeII Res., 2006, 19, 550; Cosmet. ScL Technol. Ser., 2006, 30, 205, Pigment CeII Res., 2003, 16, 101).

Tyrosinase, which is the enzyme responsible for pigmentation, is obtained at the cellular level in various stages (Pigment CeII Res. 2006, 19, 3).

When tyrosinase is synthesized, many molecules can act directly on this enzyme. Its inhibition leads to a moderate to strong decrease in melanin production. Among the most known inhibitory molecules, mention may be made of kojic acid, hydroquinone, arbutin, compounds with phenolic rings such as polyphenols, flavonoids, chlorogenic acid, p-hydroxyvanillic acid, etc. However, some of these molecules can no longer be used for cosmetic applications because of their toxicity or their mutagenic potential. During the synthesis phase of melanin, the inhibition of the formation of peroxides, especially by phenols or polyphenols, can also be used to minimize pigmentation. Anti-free radical compounds are also used for cosmetic and dermocosmetic applications. Among these are hydrophilic molecules such as ascorbic acid, lipophilic molecules such as vitamin E or alpha-tocopherol or modified hydrophilic compounds such as ascorbyl palmitate.

Other molecules have properties to limit pigmentation but their role is not yet fully known. This is the case with azelaic acid (Case Rep. Clin, Pract., Rev., 2002, 3, 204).

Of the compounds that can affect skin pigmentation, fatty acids are another family of molecules. In particular, linoleic acid has lightening properties (Archives of Dermatological Research, 1998, 290, 375, Journal of SCCJ, 1993, 27, 415, Fragrance Journal, 1990, 18, 86, Pigment CeII Research, 1990, 3, 200 JP63284109). However, these depigmenting properties are limited in direct involvement with tyrosinase, since one publication indicates that linoleic acid does not reduce tyrosinase activity to non-cytotoxic concentrations (Journal of the Society of Cosmetic Chemists, 1991, 42, 361).

It has recently been shown that fatty acids regulate skin pigmentation by degradation of tyrosinase, a hypothesis previously mentioned in two publications (Journal of Lipid Research 1999, 40, 1312, Nippon Shokukin Kagaku Kaishi 1998, 45, 295). More recently, it has been shown that polyunsaturated fatty acids such as linoleic acid and alpha-linolenic acid limit the formation of melanin, while saturated fatty acids such as palmitic or stearic acid increased pigmentation (Biochem J. , 2006, 394, 43, The Journal of Biological Chemistry, 2004, 15, 15427). It should be noted that all these publications concern fatty acids in free form.

For fatty acid esters, the literature does not mention a relevant publication concerning depigmentation. A menthyl linoleate is contained in a cream having inhibiting properties of melanin formation (JP2007161591). Esters of acids polyunsaturated fats with mono- or dihydroxy alcohols are also mentioned, associated with phenolic core molecules (JP03209305). A cosmetic formula containing vitamin E acetate, citric acid and polyunsaturated fatty acids or their esters is also described as a lightening composition (JP 01093520). Lipophilic derivatives of kojic acid, esterified with organic acids such as linoleic acid have also shown a depigmenting skin effect (JP 56079616). In all these publications, the goal is to make a lipophilic molecule already highly or moderately depigmenting to promote its skin penetration. This has also been shown with fatty acid esters of kojic acid (EP 1 566 168).

Hydroxy acids, such as, for example, malic acid, have also been made lipophilic by esterification with fatty acid anhydrides or halogenated fatty acids. These molecules can then have a depigmenting character (US5869069).

A cosmetic formulation containing the depigmenting molecules octadecenoic and thioctic acids, supplemented with an anti-UV and with ethyl linoleate, tested on 20 women led to a significant reduction in melanosis after 2 months of treatment (International Journal of Cosmetic Science, 2006, 28, 263).

The use of fatty acid amides for depigmenting or lightening applications is even more restricted or nonexistent. Phosphate fatty derivatives (phosphatidyl ester or lysophosphatidyl ester) which may or may not have an amide linkage have been presented as a cutaneous bleaching agent (JP8133944). Phospholipids having a linoleic acid at the 2-position also showed a bleaching effect at the cutaneous level (JP2005272444). Phosphated sphingosine has also been presented as a pigment-limiting molecule (J. CeII Sci., 2003, 116, 1699).

In the category of saturated fatty acid amides, mention may be made of lauroyl derivatives of aminophenols (WO 9932077). For amides derived from polyunsaturated fatty acids and their application in direct depigmentation, the literature reveals no publication.

The Applicant has found that compounds bearing an ester group and an amide group, corresponding to formula (I):

in which :

m is an integer selected from values 1 and 2;

n is an integer selected from the values 0, 1 and 2;

R1 and R3 are saturated or unsaturated carbon chains containing from 4 to 25 carbon atoms and optionally from 1 to 2 hydroxyl groups borne by distinct carbons;

R 4 is chosen from the groups -H, -OH ₁ -SH, -COOH and a linear or branched, saturated or unsaturated carbon chain of 1 to 22 carbons, terminated with a group chosen from -H, -OH, SH and -COOH showed significant depigmenting activity.

Particular importance must be given to the parameters m and n according to its value, the compounds of formula (I) are derivatives of aminoethanol or aminopropanol or aminobutanol. The aminobutanol derivatives are the ones that show the most important efficacy.

Excellent results are also obtained when R4 is a -OH group or a linear or branched, saturated or unsaturated carbon chain, of 1 to 22 carbon atoms, terminated by an -OH group.

Among the compounds of general formula (I), there may be mentioned preferably the compound of formula (Ia), the compound of formula (Ib) and the compound of formula (Ic):

The results obtained by these compounds in depigmentation tests are far superior to those of linoleic acid used alone or even in ester form, such as ethyl ester. Examples of total depigmentation have been obtained.

In the current state of knowledge on the subject, the mode of action of these molecules is not fully defined. It is likely that they intervene on several factors of the depigmentation, and in particular on the degradation of tyrosinase via the ubiquitin proteasome system. Free linoleic acid has a lightening mode of action for similar reasons (Journal of Hiological Chemistry, 2004, 279, 15427).

This category of compounds is totally new in the field of depigmentation. Indeed, the presence of a saturated fatty chain at R3 leads to particularly interesting results. This seems paradoxical, because according to all the data in the literature, the presence of saturated fatty acid and especially palmitic acid or their derivatives should greatly increase pigmentation. The compounds of formula (I) can be synthesized by methods known from the literature. It is particularly possible to cite the process described in patent application EP1644318, which consists in subjecting an aminoethanol, butanol or propanol to the action of a specific lipase to carry out the esterification of the hydroxyl group and then the amidation of the function. aminated with a fatty acid derivative.

According to a preferred form of the invention, m is equal to 1.

According to a preferred form of the invention, n is equal to 1.

According to a preferred form of the invention, X is a hydrogen atom.

According to a preferred form of the invention, R2 is a hydrogen atom.

According to a preferred form of the invention, R 1 is a mono- or polyunsaturated fatty acid chain, especially oleic, linoleic, alpha-linolenic, gamma-linolenic, punicic, eicosapentaenoic, docosahexaenoic. More preferably, R 1 is the linoleic acid chain.

According to a preferred form of the invention, R3 is chosen from linoleic or oleic acids for unsaturated fatty acids and palmitic or stearic acids for saturated carbon chain fatty acids. According to one preferred form of the invention, R4 is an -OH group.

Preferably, the content of the compositions of compounds of formula (I) ranges from 0.001 to 20% relative to the total weight of the composition and in particular from 1 to 10% relative to the total weight of the composition.

The compositions according to the invention are intended for topical application. They comprise an inert, non-toxic, cosmetically or dermatologically acceptable carrier, in combination or in admixture with the active ingredient. They may contain adjuvants commonly used in the cosmetics field, such as, for example, softening agents, gelling agents, antioxidants, solvents, filters, preserving agents, pigments or perfumes. The compositions according to the invention are in a form compatible with topical application, such as an aqueous, hydroalcoholic, hydroglycolic or oily solution, a dispersion, a suspension, an oil-in-water or water-in-oil emulsion, an aqueous or oily gel. , a cream, a milk, an ointment, a lotion, a paste, a mousse or an aerosol.

The compositions according to the invention are intended for skin depigmentation. In a nonlimiting manner, they may for example be used for one to several applications per day over part or the entire surface of the body and face to obtain a uniform skin tone.

Examples:

Evaluation of the depigmenting activity

The test is performed on the epidermis from a frozen mammoplasty of a 27-year-old woman. The epidermis are separated by incubation in 2N NaBr

1 hr. At 37 ° C.

They are then fixed in a buffered formaldehyde fixative, rinsed and brought into contact with the mixture of a L-DOPA solution with the test formulation (1: 1 v / v).

After incubation, they are rinsed and mounted between blade and cover with liquid Mounting

Medium.

The observation was performed by optical microscopy at x10 objective. shots are stored using the Leica IM 1000 data archiving software.

For each batch, several microscopic fields were analyzed using the LEICA Qwin image analysis software.

For each field, positive DOPA melanocytes were counted and the area area was measured to determine the number of melanocytes per mm ² . The results are reported in Table 1:

Table 1 Example 1 Depigmenting Activity of the Reference Compositions

Formula of compositions used:

Placebo is the emulsion without the active ingredient.

Since it was known that free linoleic acid had a lightening power, the latter was included in the test to evaluate comparatively the lightening power of the compounds of formula (I).

This result has also been compared to derivatives of linoleic acid, here in the form of ethyl ester.

As a positive control, the reference molecule in cosmetics represented by kojic acid was used.

The results are given as a percentage of pigmentation or depigmentation compared to placebo in the table below:

Table 2 Figure 1a (in the appendix) illustrates the result obtained from the L-DOPA control.

Figure 1b illustrates the result obtained from the placebo alone.

Figure 1c illustrates the result obtained from the composition containing 1% kojic acid.

Figure 1d illustrates the result obtained from the composition containing 1% linoleic acid.

Figure 1e illustrates the result obtained from the composition containing 1% of ethyl linoleate.

In this study for comparison, amides, and in particular the amide obtained between linoleic acid and aminoglycerol, of formula (II), were also included.

Table 3

Figure 1f illustrates the result obtained from the composition containing 1% amide of formula (II). Example 2 Depigmenting Activity of a Composition Containing Compound (la)

A composition containing 1% of compound of formula (Ia) was tested (same formula as in Example 1). The results are given as a percentage of pigmentation or depigmentation compared to placebo in the table below:

Table 4

FIG. 2 illustrates the result obtained from the composition containing 1% of compound of formula (Ia)

Example 3 Depigmenting Activity of a Composition Containing the Compound (Ib)

A composition containing 1% of compound of formula (Ib) was tested (same formula as in Example 1). The results are given as a percentage of pigmentation or depigmentation compared to placebo in the table below:

Table 5

FIG. 3 illustrates the result obtained from the composition containing 1% of compound of formula (Ib).

EXAMPLE 4 Depigmenting Activity of a Composition Containing Compounds (Ia) and

Proportion 2/3

+

Proportion 1/3 A composition containing 1% of mixture of the compounds of formula (la) and (1c) (ratio 2: 1) was tested (same formula as in example 1). The results are given as a percentage of pigmentation or depigmentation compared to placebo in the table below:

Table 6

Figure 4 illustrates the result obtained from the composition containing 1% 2: 1 mixture of compounds (Ia) and (Ic).

Example 5

Lightening composition containing the compound (la):

Example 6

Lightening composition containing the compound (Ib):

Example 7

Lightening composition containing the mixture (la) / (lc) (2: 1)

Example 8

Demonstration of the depigmenting activity of the products on human skin explants maintained in survival

Protocol:

The products to be tested were applied locally using a small spatula every day at the rate of 2 mg of preparation per explant.

The explants are subjected to irradiation with UVA / UVB performed at a dose of 1.125 J / cm ² from the ^6th day. The tests are carried out comparatively with the kojic acid taken as a reference substance, with an untreated control and with a placebo cream.

The melanin present at J 0, J 6 and J 12 is read.

The obtained results are coded from (-) (no effect or negative effect) to (+) (very low or very few spots), (++), few or moderate effect to (+++) (many spots or net effect).

FIG. 5 reproduces the effects on explant sections thus treated at times TO, J6 and

J12.

The attached table 7 summarizes the results obtained on the one hand with non-irradiated samples and the same samples subjected to irradiation.

Table 7

In this table: T symbolizes witnesses

R test with kojic acid E trial with a placebo

P1 test with compound-based preparation

Table 8 summarizes the results obtained after irradiation with UV rays at J12

table 8

A depigmenting effect visualization test was performed by performing a visualization of the explants by expression of T RP1 which in particular reflects the degree of maturation of the melanosomes. These results are summarized in Table 9

Table 9 This test shows that without UV action, the application of the formulations containing the product of the invention induces a clear decrease in the expression of TRP 1, reflecting an inhibition of the maturation of melanosomes. This activity is similar to that obtained with kojic acid. After UV action, a clear inhibitory action is observed with the composition containing the product of the invention. This action is of the same order of magnitude as that obtained with kojic acid.

A third test was performed on human skin explants by evaluating the melanin levels. Table 10 and Figures 6 and 7 summarize the results obtained.

Table 10

Claims

1. Cosmetic and / or dermatological compositions, characterized in that they contain as active principle at least one compound corresponding to formula (Ia):

in combination or in combination with an inert, non-toxic vehicle suitable for topical application

2. Cosmetic and / or dermatological compositions, characterized in that they contain, as active ingredient, at least one compound corresponding to formula (Ib):

3. Compositions according to claim 1, characterized in that they contain as active principle, at least one mixture formed of the compound corresponding to the formula

(Ic):

and the compound of formula la in the proportion 1/3 2/3

4. Cosmetic and / or dermatological compositions intended for topical application, characterized in that they contain, as active ingredient, at least one compound corresponding to formula (I):

in which :

m is an integer selected from values 1 and 2;

n is an integer selected from the values 0, 1 and 2;

R4 is chosen from the groups -H, -OH, -SH, -COOH and a linear or branched, saturated or unsaturated carbon chain containing from 1 to 22 carbon atoms terminated by a group chosen from -H, -OH; , -SH and -COOH, in combination or in admixture with an inert, non-toxic vehicle suitable for topical application.

5. Compositions according to claim 4, such as in the formula (I), R1 is an unsaturated fatty acid chain, in particular oleic, linoleic, alpha-linolenic, gamma-linolenic, punicic, eicosapentaenoic, docosahexaenoic.

6. Compositions according to claim 4 as in formula (I), R3 is selected from linoleic, oleic, palmitic or stearic acids.

7. Compositions according to one of the preceding claims, such that in formula (I), m is equal to 1.

8. Compositions according to one of the preceding claims, such that in formula (I), n is equal to 1.

9. Compositions according to one of the preceding claims, such that in formula (I), X is a hydrogen atom.

10. Compositions according to one of the preceding claims, such that in formula (I), R2 is a hydrogen atom.

11. Compositions according to one of the preceding claims, such that in formula (I), R4 is a linear or branched, linear or branched, saturated or unsaturated -OH or carbon chain having from 1 to 22 carbons, terminated by a grouping. -OH.

12. Compositions according to claim 4, such as in the formula (I), R4 is a group -OH.

13. Compositions according to one of the preceding claims, such that the content of compound of formula (I), la, Ib and / or Ic varies from 0.001 to 20% relative to the total weight of the composition.

14. Use of the compositions containing as active ingredient at least one compound of formula (I)

according to claims 1, 2, 3 or 4 for the production of a depigmenting preparation.