CH649987A5 - QUATERNARY DIBENZOYLMETHANE DERIVATIVES, THEIR USE AS SOLAR FILTERING AGENT AND COSMETIC COMPOSITION CONTAINING THEM. - Google Patents

Description

The present invention relates to quaternary dibenzoylmethane derivatives, to their application as a solar filtering agent and to the compositions containing these des-40 compounds, in particular to be used in the protection of the skin against UV radiation.

We know that light radiation between 290 and 400 nanometers (nm) allows browning of the human epidermis and that the area between 290 and 320 nm 45 known under the name UV.B causes erythema and burns the severity of which increases rapidly with the duration of the exposure. However, it has been found that if UV.A radiation, having a wavelength between 320 and 400 nm, causes browning of the skin, it can cause changes in the skin, in particular for sensitive skin or continuously exposed skin. to solar radiation. Furthermore, it has been found that UV.A radiations could potentiate the action of UV.B as has been described by several groups of authors and more particularly by J. WILLIS, A. KLIGMAN and J.EPSTEIN (The Journal of Investigative Dermatology Vol. 59 No. 6 page 416.1073) under the name of Photo augmentation.

It therefore appeared desirable to also try to filter UV.A radiation. 60 Dibenzoylmethane or its derivatives substituted by an alkyl or alkoxy group have already been used in non-aqueous vehicles.

Solubility in water is also a sought-after criterion for certain sunscreens, since in certain cases 65 protection is desired obtained simultaneously for the aqueous phase and for the fatty phase of the compositions in the form of emulsions frequently used in this. field. Such a distribution makes it possible to optimize the absorption of UV radiation.

3

649,987

Finally, it is known that the components of certain cosmetic preparations, in particular certain dye dyes, colored hairsprays, shampoos, styling lotions, or tinted creams do not always have sufficient light stability and that they degrade under the action of light radiation.

Consequently, it is desirable to incorporate into these preparations compounds capable of filtering light radiation and which must therefore have, in addition to the good filtering qualities, good stability and sufficient solubility in the media usually used in cosmetics and in particular in the media. aqueous.

The licensee has now discovered a new family of compounds derived from dibenzoylmethane having good filtering properties with respect to UV radiation and in particular with respect to UV.A radiation. This family of compounds also exhibits excellent solubility in an aqueous medium, good photochemical and thermal stability, good substantivity with respect to the skin so as not to be eliminated or degraded by perspiration. These compounds also have the advantage of not being toxic or irritating and of having no harmful effect on the skin.

These compounds are distributed uniformly in conventional cosmetic supports capable of forming a continuous film and can therefore be easily applied to the skin to form an effective protective film.

The invention therefore relates to new quaternary derivatives of dibenzoylmethane.

It also relates to the application as a solar filtering agent in particular with respect to UV.A radiation of these compounds and the cosmetic compositions containing i5 these compounds as a solar filtering agent.

The compounds in accordance with the present invention are essentially characterized in that they correspond to the general formula:

(RJ

3 n in which:

Ri and R2 represent a lower alkyl or hydroxyalkyl radical,

R3 represents a lower alkyl or lower alkoxy radical, n is an integer from 0 to 3,

(I)

r,

. ©

x

X "is an anion derived from a mineral or organic acid. The compounds of formula (I) above can also be in the following tautomer form (la):

H.

0

h

R

1

R,

r.

(the)

JP1

in which the different substituents have the same meaning as that indicated above.

It is understood in the following description that when talking about the compounds of formula (I), we will also include the tautomeric form of these compounds of formula (la) above.

The alkyl radical in formula (I) above preferably denotes a radical having between 1 and 4 carbon atoms and more particularly a methyl, ethyl, propyl radical, the alkyloxy radical more particularly denotes a methoxy or ethoxy butoxy radical, X "designates in particular a sulfate, methosulfate, halide anion such as chloride or bromide, as well as any other cosmetically acceptable anion. The quaternary ammonium group is preferably in position 4 of the benzene ring.

The cosmetic compositions intended to protect the epidermis against ultraviolet radiation in particular against UV.A radiation in accordance with the present invention can be in the various forms usually used for this type of composition. They can in particular be presented in solution in the form of a lotion, in emulsion in the form of cream, or gel milk, or be packaged in aerosol in the form of foam or spray.

They can contain the cosmetic adjuvants usually used in this type of composition, such as thickeners, softeners, superfatters, emolients, wetting agents, surfactants, preservatives, anti-foaming agents, oils, waxes, dyes and / or pigments having the function of coloring the composition

649 987 4

itself or the skin, preservatives, and any other sunscreen ingredients. They can in particular be associated with dient usually used in cosmetics. sun filters selectively filtering radiation

The compounds according to the invention are present from UV.B. Mention may be made for this purpose as a solar filtering agent preferably in proportions by weight of between 0.05 of water-soluble filtering agents such as derivatives of and 10% relative to the total weight of the composition as 5 benzylidene camphor described in the patent or request for bre-

Solubilization solvent, water, a French monoalvet 2 199 971, from the holder and more particularly cool or lower polyalcohol or a hydroalcoholic solution, methyl (sulfate of (oxo -2- bornylidene -3methyl) -4-) can be used. phenyl-

The more particularly preferred mono or polyalcohols are trimethylammonium,

chosen from ethanol, isopropanol, propylene glycol or The compounds according to the invention can also be as-

glycerin. 10 associated with liposoluble compounds or oils having

Among the particularly preferred embodiments, solar filtering properties such as in particular oil, mention may be made of sun creams or milks, additionally comprising coffee. As lipophilic solar filtering agent, mention may be made of the compounds in accordance with the invention, fatty alcohols, derivatives of salicylic acid such as 2-ethyl salicylate.

oxyethylenated fatty alcohols, esters of fatty acids, hexyl oils, homomenthyl salicylate, natural or synthetic acid derivatives, waxes in the presence of water. Cinnamics such as ethylhexyl -2-p-methoxycinnamate,

Another embodiment consists of lo-2-ethoxy-ethyl-p-methoxycinnamate, acid derivatives such as oleoalcoholic lotions based on para-aminobenzoic alcohol such as amyl paraaminobenzoate,

such as ethanol, polyethylene glycol and / or octyl para dimethylaminobenzoate, benzo- derivatives

glycerin. phenone such as 2-hydroxy -4- methoxybenzophenone,

The process for protection against ul- 2,2'-dihydroxy -4- methoxybenzophenone radiation, derivatives of cam-

traviolets of cosmetic compositions consists essentially of phre such as (methyl -4- benzylidene) -3- associated camphor

ment to introduce into these cosmetic compositions, optionally with isopropyl -4- dibenzoylmethane, at least one compound corresponding to the above-mentioned formula (I) 3-benzylidene camphor.

in the proportions indicated above. Such compositions can be constituted in particular by the compounds. It goes without saying that this list of filters which can be used in hair combinations such as hair sprays, lotions with the compounds according to the present invention is not to be styled. plasticizers, treatment-limiting styling lotions.

The detergents or detanglers, shampoos, color shampoos, etc. The compounds according to the invention are new and may be dyes, dye compositions for hair, preparations prepared by quaternization of known or new products.

make-up, treatment creams for the epidermis or calves prepared by adaptation of known methods such as as well as any other cosmetic composition which may, for example, those described in French patent 2 326 405.

Because of these constituents, they feel problems of stability at the end. One can essentially use two diagrammatic processes storage in the light. by the following reactions:

The compositions in accordance with the invention may also. The following examples are intended to illustrate the invention, in addition to containing compounds of formula (I), others without, however, being limiting in nature.

Method 1.

(1) HBr

(2) Br2

f.Vi C-H.ONa 2 to

(4) Ho0, HCl then neutralization

R-

-CR

•not

0

ii c

® / R1 R Y

# v / 1 R-, x

N-R ,,

R.,

X

G

Method 2

5

649,987

0

FL

io * -

R ~

where

ch. + c.hccx; o j 2

O

/

not

\

R

1

Na-NR,

claisen condensation

>

CH-

r-

The groups Rb R2, R3, Xe having the meanings indicated above.

Example 1

Preparation of 4-trimethylammonio-dibenzoylmethane methosulfate.

A) Method 1

1st step: Preparation of 4-dimethylamino benzylidene acetophenone. In a 4-liter reactor equipped with a thermometer, an addition funnel, a condenser and a stirrer, 1 liter of a 10% aqueous sodium hydroxide solution, 800 ml of ethanol and 240 g of acetophenone. The mixture is cooled to 20-25 ° C and 298 g of p-dimethylami-nobenzaldehyde are added at this temperature for 2 hours.

The reaction mixture is stirred for 48 hours and the solid obtained is filtered, washed with water, dried and recrystallized from isopropyl alcohol. 481 g of chalcone are obtained having a degree of purity greater than 99%. Melting point = 113 ° C.

2nd step: Preparation of 4-dimethylamino dibenzoylmethane. In a 4 liter reactor equipped, 251 g of chalcone and 1 liter of etanol are charged. 250 ml of an alcoholic solution of HBr 4.2 N are added with stirring at room temperature. Stirring is continued for 30 minutes, the alcohol is removed under vacuum and the solid washed with isopropyl alcohol. After drying, 327 g of chalcone hydrobromide are obtained.

The dosage gives a purity greater than 99%.

In a 2 liter reactor, 327 g of chalcone hydrobromide are dissolved in 600 ml of chloroform. 174.2 g of bromine in 200 ml of chloroform are added over approximately 2 hours while maintaining the temperature between 15 and 20 ° C.

After addition, the mixture is left to stand overnight and then precipitated with 5 liters of isopropyl ether. The solid is washed several times with isopropyl ether, drained and dried under vacuum. 500 g of brominated product are obtained which are dissolved in 400 ml of alcohol.

Then 1.51 sodium ethylate (prepared from 80 g of sodium in 1.6 liters of ethanol) is added over 20 minutes and the mixture is brought to reflux for 1 hour 45 minutes the mixture is neutralized by addition concentrated hydrochloric acid (about 50 ml), brought to reflux for 5 to 10 minutes and then add 500 ml of water. By cooling the product precipitates, it is drained, dried under vacuum and recrystallized from ethyl acetate.

112 g of dibenzoylmethane are obtained. Melting point = 150 ° C.

40% theory C 76.39 H 6.41 N 5.24% found C 76.43 H 6.40 N 5.07 NMR (dcei3) consistent with the structure.

3rd step: Preparation of 4-trimethylammonio-dibenzoylmethane methosulfate. In a 2 liter 45 equipped reactor, a mixture of 112 g of the above product and 950 ml of ethyl acetate are brought to 80 ° C. until dissolved. 386 ml of dimethyl sulphate are introduced over 5 minutes and the mixture is heated at 80-100 "C for 20 hours.

The mixture is cooled to 10 ° C., the quaternary is drained, 50 washed with ethyl acetate and dried under vacuum.

155 g of quaternized dibenszoylmethane are obtained. Melting point 170-180 ° C.

% theory C 58.01 H 5.89 N3.56% found C 58.00 H 5.93 N3.54 55 max (EtOH) = 345 nm (s = 15600).

The compound thus obtained corresponds to the formula:

ch3 so4

©

• ch.

649987

6

B) Method 2

7.8 g of sodium amide in suspension in 50 ml of toluene are placed in a reactor equipped and maintained under nitrogen. 12 g of acetophenone in solution in 20 ml of toluene are introduced over approximately 10 minutes. After 1 hour of stirring 40 g of p. ethyl dimethylaminobenzoate dissolved in 120 ml of toluene are introduced to their whole. The mixture is stirred at room temperature for 48 hours.

After adding 200 ml of toluene and then 11 of dilute hydrochloric acid, the organic phase is separated, dried and concentrated in vacuo.

The residue is recrystallized from ethyl acetate to obtain 12.5 g of 4-dimethylamino-dibenzoylmethane. The compound thus obtained is quaternized under the same conditions as in step 3 of process 1.

The preparations of the compounds of Examples 2 and 3 are identical to those of Example 1.

Example 4

Preparation of 4-trimethylammonio dibenzoylmethane chloride. 100 g of trimethyl ammonio-4 dibenzoylmethane methosulfate are dissolved in a mixture of 150 ml of water and 150 ml of ethanol.

250 g of IRA 400 resin in the form of CI9 are placed in a column to be chromatographed and then rinsed with 1 liter of 50/50 water-ethanol mixture.

The previously prepared solution is poured onto the resin until it fully penetrates it. After 1 hour of waiting the elution is started with a flow rate of about 50 drops / min using the 50/50 ethanol-water mixture. The recovered solution is evaporated in vacuo and the residue taken up in ethyl acetate. The crystals obtained are drained, washed with ethyl acetate and dried under vacuum, to obtain 75 g of trimethylammonium chloride -4-dibenzoylmethane.

Table 1 brings together the characteristics of these molecules.

Table 1

C - CHo-C-

2 II

0

/ \\

CH.

NOT

- CH ^; X °

ch3

Ex Ri

2

3

4

Position of R3

-CH3 4 -OCH3 4 H 4

Xmax

CH3S04 345

8 = 25500 (ethanol) CH3S04- 350

8 = 29000 (ethanol) Cl "345

e = 21100 (ethanol)

Molar mass Melting point 407.49 169

423.49 148

317.82 180

These 3 products are soluble in water, ethanol. e = molar extinction coefficient

Table II

Examples 5 to 7 The compounds of Table II below are prepared in the same way as that described in Example 1 using method 2.

Ex. R3 R'3 R?

5 oc4h9 H CH3

X ©

CH3S04e x®

Elementary analysis * Absorption Theory Found (solvent) imax

C 57.13 H 6.41 N 2.90 S 6.61

57.55 6.7 3.01 6.23

359 nm £ = 19300 (Ethanol)

Melting point ° C

151

Table II (continued)

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649,987

Ex. R}

R'3

R,

X @ Elementary analysis' Absorption

Found Theory (solvent) Xmax

Melting point ° C

6

h h

ch2-ch2-oh

Bre

C55.6

55.8

350 nm

h 5.8

5.66

s = 13200

N 3.4

3.6

(Ethanol)

Brl9.5

10.1

7

och3

och3

ch3

ch3so4q

C53.5

53.3

366 nm

h 5.72

6.06

8 = 6000

N 2.97

2.95

(Water)

s 6.78

6.3

127

163

* These products crystallize with a molecule of water.

Examples of compositions

Composition 1

Solar cream

Cetylstearyl alcohol + oxyethylated oleocetyl alcohol born with 25 moles of ethylene oxide 7.00 g

Glycerol monostearate 2.00 g

Vaseline hijiile 15.00 g

Dimethylpolysiloxane 1.50 g

Ceyl alcohol 1.50 g

3-benzylidene camphor 2.50 g

Glycerin 20.00 g

Compound of Example 1 2.00 g

Preservatives 0.30 g

Perfume 0.60 g

Sterile demineralized water ... q.s.p 100 g

This emulsion is produced according to conventional techniques. The camphor 3-benzylidene is dissolved beforehand in the fatty phase and the compound of Example 1 in the aqueous phase contains the glycerin and the emulsion is prepared.

Composition 2

Sun milk

Cetylstearyl alcohol + oxyethylated oleocetyl alcohol born with 25 moles of ethylene oxide 5.00 g

Vaseline oil 6.00 g

Isopropyl myristate 3.00 g

Silicone oil 1.00 g

Cetyl alcohol 1.00 g

30% aqueous solution of 3- (4-trimethylammonio-benzylidene) camphor methosulfate (UV.B filter) 13.33 g Compound of Example 1 2.00 g

Preservatives 0.30 g

Perfume 0.50 g

Sterile demineralized water ... q.s.p 100 g

The two foilers are dissolved in the aqueous phase: the emulsion is produced according to conventional techniques.

Composition 3

Solar cream

Oxyethylenated cetylearyl alcohol with 16 moles of ethylene oxide 2.00 g

Mixture of mono and glycerol distearate 4.00 g

Cetyl alcohol 4.00 g

Butyl stearate 5.00 g

Vaseline oil 5.00 g

1-2-propane-diol 7.00 g p-dimethylamino octyl benzoate 2.00 g

Silicone oil 0.125 g

25

Compound of Example 4 2.00 g

Preservatives 0.30 g

Perfume 0.60 g

Sterile demineralized water ... q.s.p 100 g

Octyl p-dimethylamino benzoate is dissolved in the fatty phase and the compound according to the invention in water.

Composition 4 Aerosol foam 3o Sipol wax Vaseline oil Isopropyl palmitate Glycerin Preservatives 35 Compound of Example 1 Perfume

Sterile demineralized water ...

3.50 g 6.00 g 3.00 g 10.00 g 0.30 g 2.00 g 0.50 g 100 g

This composition is conditioned in an aerosol container in proportions of 87% of composition and 13% of Freon F12.

Composition 5

Oleo alcoholic lotion Glycerin 5.00 g

45 Polyethylene glycol 400 0.50 g

Perfume 2.00 g

Compound of Example 1 2.00 g

Ethanol at 96 ° 50.00 g

Sterile demineralized water ... q.s.p 100.00 g

50

Composition 6

Solar cream

Cetylstearyl alcohol + oxyethylenated oleocetyl alcohol with 25 moles of ethylene oxide 7.00 g 55 Glycerol monostearate 2.00 g Vaseline oil 15.00 g Dimethylpolysiloxane 1.50 g Cetyl alcohol 1.50 g 3-benzylidene camphor 2 , 50 g n / a Glycerin 20.00 g Compound of Example 5 2.00 g Preservatives 0.30 g Perfumes 0.60 g Sterile demineralized water ... qs 100 g 65 This emulsion is produced according to conventional techniques. The camphor 3-benzylidene is dissolved beforehand in the fatty phase and the compound of Example 5 in the aqueous phase containing the glycerin and the emulsion is prepared.

649,987

Composition 7 Aerosol foam Sipol wax Vaseline oil Isopropyl palmitate Glycerin Preservatives Compound of example 6 Perfume

Sterile demineralized water ...

This tion is conditioned in an aerosol container in proportions of 87% of Freon F12 composition.

3.50 g 6.00 g 3.00 g 10.00 g 0.30 g 2.00 g 0.50 g

Composition 8 Sun milk

Cetylstearyl alcohol + oxyethyl oleocetyl alcohol

born with 25 moles of ethylene oxide s Vaseline oil Isopropyl myristate Silicone oil Cetyl alcohol

30% aqueous solution of 3- (4-trimethylammonio-

100 g io benzylidene) camphor methosulfate (UV.B filter)

compound and 13% of

5.00 g 6.00 g 3.00 g 1.00 g 1.00 g

Composed of Example 7 Perfume Preservatives

Sterile demineralized water ... q.s.p 15 The two filters are dissolved in the aqueous phase: Va.-emulsion is produced according to conventional techniques.

13.33 g 2.00 g 0.30 g 0.50 g 100 g

VS

Claims (8)

649987 CLAIMS I. Derivative of dibenzoylmethane characterized in that it corresponds to the formula: or its tautomeric form r, AT" in which Rj and R2 represent an lower alkyl or hydroxyalkyl radical, R3 represents the lower alkyl or lower alkyl radical, n is an integer from 0 to 3, X is an anion derived from a mineral or organic acid. 2. Denzenzoyl methane derivative according to claim 1, characterized in that it is chosen from: 4-trimethylammonio-dibenzoylmethane methosulfate, trimethylammonio-4-methyl-4 'dibenzoylmethane methosulfate, 4-trimethylammonio-4-methoxy-methoxy-dibenzoylmethane methosulfate, trimethylammonio-4 dibenzoylmethane chloride, 4-trimethylammonio-2-butoxy-2'-dibenzoylmethane methosulfate, (dimethyl, P-hydroxyethyl) 4-ammonio-dibenzoylmethane bromide, trimethylammonio-4, dimethoxy-2 ', 4' dibenzoylmethane methosulfate. 3. Cosmetic composition, characterized in that it contains at least one compound as defined in claim 1 or 2 in a cosmetically acceptable medium. 4. Composition according to claim 3, characterized in that it is in the form of solution, lotion, emulsion, cream, gel, foam or milk optionally packaged in aerosol form. 5. Composition according to one of claims 3 or 4, characterized in that it contains thickeners, softeners, superfatters, emollients, humectants, surfactants, preservatives, anti-foaming agents, coulourants and / or pigments, oils, waxes, perfumes. 6. Composition according to one of claims 4 to 5, characterized in that the compound of formula (I) is present in the proportions of between 0.05 and 10% by weight relative to the total weight of the composition. 7. Composition according to one of claims 4 to 6, characterized in that it also contains other water-soluble or liposoluble solar filtering agents having a filtering action with respect to UV.B radiation. 8. Method for protecting cosmetic compositions containing components sensitive to UV radiation, characterized in that at least one compound as defined in claim! Is introduced into these compositions. 35