DE3129493A1 - Quaternary dibenzoylmethane derivatives, their use as sunscreen agents, and cosmetic agents which contain these derivatives - Google Patents

Description

The invention relates to quaternary dibenzoylmethane derivatives, their use as a sunlight filtering agent Agent, as well as means containing these compounds and in particular for protecting the skin against UV radiation be used.

It is known that light radiation between 290 and 400 nanometers (niti) causes the epidermis to tan and that the range between 290 and 320 nm, which is known as UV-B, causes reddening of the skin and Causes skin burns, the extent of which increases rapidly with the duration of the irradiation. It has also been found that if the UV radiation A, which comprises the wavelength range between 320 and 400 nm, the tanning causes the skin, it also changes the same, especially the sensitive skin or those areas of the skin, which are continuously exposed to solar radiation

are, can cause. It has also been determined / that the UV radiation A is able to intensify the effect of the UV radiation B, as stated by various groups of authors and in particular by J. Willis, A, Kligman and J. Epstein in "The Journal of Investigative Dermatology, Vol. 59, No. 6, page 416, 1073, under the name "Photo Augmentation" has been described.

It therefore seems desirable to try to filter UV radiation A as well.

Dibenzoylmethane or its derivatives, which by a Alkyl or alkoxy groups have been used as non-aqueous carriers.

The solubility in water is also a desired criterion for certain sun filters, because one would like in different cases at the same time in the 'aqueous phase as. also in the fat phase of the funds, which in often in the form of emulsions in this area, achieve protection. Such a distribution is allowed an optimization of the absorption of UV radiation.

It is also known that components of certain cosmetic preparations, in particular certain dyes in No dyes, colored hairsprays, shampoos, lotions for the water wave or colored creams always have sufficient stability against the action of light and that they are under the action of Decompose rays of light.

Consequently, it is desirable to use in these preparations

eiiipfxn ^ J-iGheh compounds to incorporate light filters, ',. ■■' which atTsser- their good filtering properties

excellent stability and sufficient solubility in the milieus which are usually

- are used, especially in an aqueous environment, '. exhibit. . '·

The; "- Applicant in" now has a new group of connections found which are derived from dibenzoylmethane and which are resistant to UV radiation and especially to UV ... ^ Radiation A, have good filtration properties. These The group of compounds also shows excellent solubility in an aqueous medium, a good photochemical one and thermal stability, good substantivity, towards .der H, aut in such a way that the means through perspiration cannot be eliminated or reduced. These compounds also have / the. Advantage on the fact that they are non-toxic or irritating and otherwise no;; show harmful effects on the skin.

- These connections are evenly distributed in the classic cosmetic carriers, which one form continuous film and they ^ can with ease to be distended on the skin where-they. an effective one Form a protective film.

. --The invention includes; give me new quaternary dibenzoylmethane derivatives. It also includes the use of these lanyards as the "agents that filter sunlight, especially

- especially against UV radiation A and cosmetic products, which these compounds act as sorineiifiltrating agents

--- 'included, a. ^x ^ f .- · .-; • r

The invention also comprises a method for protecting against solar radiation using these compounds. ■

Further features of the invention are described in the description can be found in the following examples.

The compounds according to the invention are essentially characterized according to the following general formula:

wherein R ₁ and R _{2 represent} a lower alkoyl or lower hydroxyalkoyl radical, R ^ represents a lower alkoyl or lower alkoyloxy radical, η represents an integer from 0 to 3, X represents an anion derived from an organic or inorganic acid.

The compounds of the above formula (I) can also are in the following tautomeric form (Ia):

wherein the various substituents have the same meaning as given above.

It can be assumed that when the compounds according to formula (I) are mentioned in the course of the description, these also include the tautomeric form of these compounds according to the above formula (Ia). ■■

The alkoyl radical in the above formula (I) preferably denotes a radical having 1 to 4 carbon atoms, particularly preferably a methyl, ethyl or propyl radical; the alkoyloxy radical is preferably a methoxy, Ethoxy or butoxy radical; X ~ denotes in particular a sulfate, methosulfate or halide anxon, such as chloride or bromide, as well as any other cosmetically acceptable anion. The quaternary ammonium group is preferably located in position 4 of the benzene ring.

The cosmetic means to protect the epidermis ultraviolet radiation, in particular against UV radiation A according to the invention, can in different Forms exist as they are common for this type of

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Funds are used. In particular, you can use * in the form a lotion, an emulsion in the form of a cream or milk, a gel, or in the form of a foam or a spray conditioned as an aerosol.

You can use cosmetic auxiliaries as they are usually in this type of agent used include, such as thickeners, emollients, superfatting agents, Emollients, humectants, surfactants Agents, preservatives, antifoams, oils, waxes, dyes and / or pigments, whose function it is is to color the product itself or the skin, preservatives, as well as all additives commonly used in cosmetics.

The compounds according to the invention are preferred in amounts by weight between 0.05 and 10%, based on the total weight of the agent; as a solubilizing solvent water, a lower monoalcohol or polyalcohol or an aqueous-alcoholic solution can be used will. Particularly preferred mono- or polyalcohols are ethanol, isopropanol, propylene glycol or glycerine.

Among the particularly preferred embodiments are to name the Sonnoncreines and Sonnenmilch, which besides the compounds according to the invention, fatty alcohols, oxyethylated Contains fatty alcohols, fatty acid esters, natural or synthetic oils, waxes, in the presence of water.

Lotions represent a further preferred embodiment represent how the oil-based alcoholic lotions

* as a solution

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a lower alcohol such as ethanol, polyethylene glycol and / or glycerine.

The procedure for protecting cosmetic products against ultraviolet radiation essentially consists in: that in these cosmetic agents at least one compound corresponding to the formula mentioned above (I) is incorporated in the proportions given above. Among these means, in particular capillary agents, such as hairsprays, lotions for plasticizing Water wave, water wave lotions for treatment or detangling,

Shampoos, tinting shampoos, hair dyes, Make-up products, creams for the treatment of the epidermis, and all other cosmetic products which have stability problems in terms of their constituents when stored in the light.

The agents according to the invention can, in addition to the compounds of the formula (I) contain other solar filters, they can be associated with such solar filters in particular be, which filter the UV radiation B selectively. Here, as the sunlight filtering agents are those water-soluble sun filters, such as the benzylidene camphor derivatives, as described in the French patent application or »the corresponding patent 21 99 971 * are, in particular (Oxo-2-bornyliden-3-methyl) -4-pheny 1 tr ime thy lanunonium-me thy I sulfate »

The compounds according to the invention can also be mixed with fat-soluble compounds or with oils that contain the Have sunlight filtering properties associated

* the applicant

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especially like with coffee oil. The following lipophilic agents that filter sunlight are: salicylic acid derivatives, such as 2-ethyl hexyl salicylate, homomenthyl salicylate, Cinnamic acid derivatives, such as ethylhexyl 2-p-methoxycinnamate, 2-ethoxy-ethyl-p-methoxycinnamate, paraaminobenzoic acid derivatives, such as amyl paraaminobenzoate, octylparadimethylaminobenzoate, Benzophenone derivatives, such as 2-hydroxy-4-methoxybenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone, Camphor derivatives, such as CMethyl-4-benzylidene) -3-camphor, possibly associated with isopropyl-4-dibenzoylmethane, 3-benzylidene camphor.

It goes without saying that this list is appropriate Filters as they can be used in association with the compounds according to the invention, not limiting should be.

The compounds according to the invention are new and can by quaternizing known products or by adapting known processes, such as those in the French Patent 23 26 405 are described.

Essentially two methods can be used: which are represented schematically by the following reactions:

The following examples are intended to explain the invention in more detail without restricting it.

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Procedure 1

> = -

(1) HBr

(2) Br ₂

(3) C ₂ H ₄ ONa

(4) H ₂ O ₅ HCl then neutralization

Procedure 2

-CH ₃ + C ₂ H ₅ OCO

ClaiserJ NaNH,

-Condensation

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The radicals R ₁ , R 1, R ₃ and X have the meanings given above.

example 1

Manufacture2_von_TrimethYlanmonio-4_dibenzoYliriethan2

(A) Procedure 1

1st step: Production of dimethylamino-4 benzylidene acetophenone. In a 4 liter reaction vessel equipped with a thermometer, an addition ampoule, a Cooling and a stirrer, 1 liter of an aqueous solution of 1O% sodium hydroxide, 800 ml of ethanol and 240 g of acetophenone mixed. The mixture is cooled to 20 to 25 ° C and 298 g of p-dimethylaminobenzaldehyde added within 2 hours at this temperature.

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, which has a degree of purity of over 99 % . Melting point: 113 ° C.

2nd step: Production of dimethylamino-4-dibenzoylmethane. In an appropriately equipped 4 liter reaction vessel 251 g of chalcone and 1 l of ethanol are added. 250 ml of an alcoholic HBr solution (4.2 N) are under

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Stirring added at room temperature. Stirring is continued for an additional 30 minutes, then the alcohol in vacuo evaporated and the solid washed with isopropyl alcohol. After drying, 327 g of chalcone bromohydrate are obtained.

The determination shows a degree of purity of over 99%.

327 g of chalcone bromohydrate are dissolved in a 2 liter reaction vessel in 600 ml of chloroform. There are 174.2 g of bromine in 200 ml of chloroform within about 2 hours while maintaining added at a temperature between 15 and 20 ° C. After the addition, the mixture is left for one night stand, then precipitated with 5 l of isopropyl ether. The pesticide is washed several times with isopropyl ether, centrifuged and dried in vacuo. 500 g of the brominated product are obtained, which is dissolved in 400 ml of alcohol dissolves.

Thereupon 1.5 l of sodium ethylate (prepared from 80 g of sodium in 1.6 l of ethanol) are added over the course of 20 minutes and then reflux the mixture for 1 hour and 45 minutes. The mixture becomes more concentrated by adding Hydrochloric acid (approx. 50 ml) neutralized, refluxed for 5 to 10 minutes, then 500 ml are added Water too. The product precipitates on cooling, it is centrifuged, dried in vacuo and dissolved in ethyl acetate recrystallized.

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

Analysis Values - Calculated (%) C 76.39 H 6.41 N 5.24

found (%) 76.43 6.40 5.07

RMN (CDCl ₃ ) according to the structure.

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3rd step: Manufacture of trimethylaitimonio-4-dibenzoylmethane methosulphate. In an equipped 2-liter reaction vessel, a mixture of 112 g of the above product and 950 ml of ethyl acetate is brought ^{to 80 ° C. until it dissolves.} 386 ml of dimethyl sulfate are then added over the course of 5 minutes; the mixture is heated to 80 to 100 ° C. for 20 hours.

The mixture is then cooled to 10 ° C, the quaternary Product is centrifuged, washed with ethyl acetate and dried in vacuo.

155 g of quaternized dibenzoylmethane are obtained. Melting point 170 to 180 ° C.

Analysis values - calculated (%) C 58.01 H 5.89 N 3.56

found (%) 58.00 5.93 3.54

max (EtOEI) = 345 run (£ = 15600).

The compound obtained in this way corresponds to the formula:

O O Il U C. C.

CH ₃ SO ₄

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(B) Procedure 2

7.8 g of sodium amide in suspension in 50 ml of toluene are placed in a suitably equipped reaction vessel which is kept under nitrogen. 12 g of acetophenone, dissolved in 20 ml of toluene, are added within approx. 10 minutes
brought in. After stirring for 1 hour, 40 g of ethyl p-dimethylaminobenzoate, dissolved in 120 ml of toluene, are added
once to. The mixture is stirred at room temperature for 48 hours.

After adding 200 ml of toluene and then 1 liter of dilute hydrochloric acid, the organic phase is separated off and dried and concentrated in vacuo.

The residue is recrystallized from ethyl acetate, 12.5 g of dimethylamino-4dibenzoylmethane being obtained. The compound obtained in this way is under
the same conditions as given in step 3 of method 1, quaternized.

The compounds of Examples 2 and 3 are prepared in the same way as in Example 1.

Example 4

chloride

10Og trimethylammonio-4-dibenzoylmethane-niethosulfat are in one Dissolved mixture of 150 ml of water and 150 ml of ethanol.

250 g of the resin IRA 400 in CI form are put into a chromatographic Given column and 1 1 of a water-ethanol mixture (50/50) rinsed.

The previously prepared solution is applied to the resin until it is completely absorbed by it. You wait 1 hour and start eluting with
a throughput

of approx. 50 drops per minute, using an ethanol-water mixture (50/50). The solution obtained
is evaporated in vacuo and the residue is taken up in ethyl acetate. The crystals obtained are centrifuged, washed with ethyl acetate and dried in vacuo, 75 g of trimethylammonio-4-dibenzoylmethane chloride being obtained.

In Table 1 are the properties of these molecules summarized.

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Table 1

E.g"
No. ^R 3 Position:
from R ₃ X P ^ max mol.
Dimensions Enamel
Point 2 -CH ₃ 4th CH ₃ SO ₄ " 345
£ = 25,500
(Ethanol) 407.49 169 3 -OCH ₃ 4th CH ₃ SO ₄ " 350
β = 29,000
(Ethanol) 423.49 148 4th H 4th Cl " 345
£ = 21,100
(Ethanol 317.82 180

These three products are soluble in water, ethanol. £ _ = molar extinction coefficient

Examples 5 to 7

Set up in the same way as in Example 1 using Method 2, the compounds listed in Table 2 below.

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Table 2

E.g. R. j V H _R. X ⁶ Elemental analysis * 57.13 ; found 55 absorption Enamel No. J calculated 6.41 7th (Solvent with point ⁰ C OC H 2.90 57, 01 tel) A. max 5 CH ₀ CH SO ' C. 6.61 6, 23 359 nm 151 H j H 55.6 3, 8th £ = 19300 N 5.8 6, 66 (Ethanol) H S. 3.4 55, 6th 6th -CH ₀ -CH ₀ -OH Br " C. 19.5 5, 1 350 nm 127 OCH ₀ 2 2 H 53.5 3, 3 i = 13200 ο N 5.72 20, 06 (Ethanol) OCH. Br 2.97 53 95 7th ■ CH ₀ CH ₀ SO. " C. 6.78 6, 3 366 nm 163 j H 2, £ = 6000 N ...... 6 / (Water) S.

These products crystallize with one molecule of water

CD-P-CD CO

Examples of the preparation of the agents according to the invention

Cetostearyl alcohol + oleocetyl alcohol,

oxyethylated with 25 moles of ethylene oxide 7.00 g

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

Glycerine 20.00 g

Compound of Example 1 2.00 g

Preservative 0.30 g

Perfume . 0.60 g

demineralized sterile water up to 100 g

This emulsion is processed according to classical methods.
You first dissolve 3-benzylidene camphor in the fat phase and
the compound of Example 1 in the aqueous phase, which contains the glycerine, and the emulsion is prepared.

Medium_2 £ _Sunmilk

Cetostearyl alcohol + oleocetyl alcohol,

oxyethylated with 25 moles of ethylene oxide 5.00 g

Vasilin oil 6.00 g

Isopropyl myristate 3.00 g

Silicone oil 1.00 g

Cetyl alcohol 1.00 g

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30% aqueous solution of 3- (4-

Trimethylammonio-benzylidene) fighter

methosulfate (filter UV-B) 13.33 g

Compound of Example 1 2.00 g

Preservatives 0.30 g

Perfume 0.50 g

Demineralized sterile water up to 100 g

The two filters are solubilized in the aqueous phase; the emulsion is prepared according to classic methods.

Medium_3 ^ _Suncream

Cetostearyl alcohol, oxyethylated with

16 moles of ethylene oxide 2.00 g

Mixture of glycerol mono- and di-

stearate 4.00 g

Cetyl alcohol .. 4.00 g

Butyl stearate, 5.00 g

Vaseline oil 5.00 g

1-2 propanediol 7.00 g

Octyl p-dimethylamino-benzoate 2.00 g

Silicone oil 0.125g

Compound of Example 4 2.00 g

Preservatives 0.30 g

Perfume 0.60 g

demineralized, sterile water up to 100 g

The octyl-p-dimethylamino-benzoate is in the fatty phase

and the compound according to the invention dissolved in water.

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i? ittel_4 ^ _Aerosol foam

Sipol wax 3.50 g

Vaseline oil 6.00 g

Isopropyl palmitate 3.00 g

Glycerine 10.00g

Preservatives 0.30 g

Compound of Example 1 2.00 g

Perfume 0.50 g

demineralized, sterile water up to 100 g

This agent is conditioned in an aerosol container in proportions of 87% of the agent and 13% of FreonFi2.

Medium_5: Oil-alcoholic lotion

Glycerin '- 5.00 g

Polyethylene glycol 400 - '0.50 g

Perfume 2.00 g

Compound of Example 1 2.00 g

Ethanol at 96 ° 50.00 g

demineralized, sterile water up to 100 g

Middle 1_6l_§ sun cream Cetylsteary alcohol 4- oleocetyl alcohol,

oxyethylated with 25 moles of ethylene oxide 7.00 g

Glycerol monostearate 2.00 g

Vaseline oil 15.00 g

Dimethylpolysiloxane 1.50 g

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Cetyl alcohol 1.50 g

3-benzylidene camphor 2.50 g

Glycerine. 20.00 g

Compound of Example 5 2.00 g

Preservatives 0.30 g

Perfumes 0.60 g

demineralized, sterile water up to 100 g

This emulsion is prepared using classic methods.
You first dissolve 3-benzylidene camphor in the fat phase and
the compound of Example 5 in the aqueous phase,
which contains the glycerine, and prepares the emulsion.

Medium_7 ^ _Aerosol foam

Sipol wax 3.50 g

Vaseline oil 6.00 g

Isopropyl palmate 3.00 g

Glycerine 10.00 g

Preservatives 0.30 g

Compound of Example 6 2.00 g

Perfume 0.50 g

Demineralized, sterile water up to 100 g

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

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Medium_§ £ _Sun milk

Cetostearyl alcohol + oleocetyl alcohol, oxyethylated with 25 moles of ethylene oxide

Vaseline oil 1 isopropyl myristate Silicone oil ceryl alcohol

30% aqueous solution of 3- (4-trimethylammonio-benzylidene) fighter methosulphate (Filter UV-B)

Compound of Example 7 Preservatives Perfume

demineralized sterile water except for

The two filters are solubilized in the aqueous phase; the emulsion is prepared according to classic methods.

5.00 G 6.00 G 3.00 G 1, 00 G 1, 00 G 13.33 G 2.00 G 0.30 G 0.50 G 100 G

Claims (1)

312 35 207 m / wa L'OREAL, PARIS / B ¹ FRANCE Quaternary dibenzoylmethane derivatives, their use as sun filter agents, and cosmetic agents which contain these derivatives PATENT CLAIMS Quaternary dibenzoylmethane derivatives corresponding to the formula and the corresponding tautomeric compound wherein R- and R _{2 represent} a lower alkoyl or lower hydroxyalkoyl radical, R _{3 represents} a lower alkoyl or lower alkoyloxy radical, η represents an integer from 0 to 3, X represents an anion derived from an inorganic or organic acid. 2. Quaternary Dibenzoylmethande'rivate, characterized in that they are composed of the following Connections can be selected: Trimethylammonio-4-dibenzoylmethane methosulfate, Trimethylammonio-4 methyl-4 'dibenzoylmethane methosulf at, trimethylammonio-4 methoxy-4 'dibenzoylmethane-methosulf ate, trimethylammonio-4-dibenzoylmethane chloride, Trimethylammonio-4 butoxy-2 'dibenzoylmethane methosulf ate, (dimethyl, ß-hydroxyethyl) ammonio-4 dibenzoylmethane bromide, Trimethylammonio-4, dimethoxy-2 ^f , 4 'dibenzoyl methane methosulfate. ο Cosmetic agent, characterized that there is at least one of the compounds defined in claims or 2 in an acceptable contains cosmetic medium. 4. Means according to claim 3, characterized in that that it is in the form of a solution, a lotion, an emulsion, a cream, a gel, a foam or a milk, optionally conditioned as an aerosol, is present. 5. Agent according to one or more of claims 3 or 4, characterized in that it Thickeners, softeners, superfatting agents, Softeners, humectants, surface-active agents Agents, preservatives, antifoams, dyes and / or pigments, oils, waxes and / or perfumes contains. β » Agent according to claim 4 or 5, characterized in that the compound of the formula (I) is present in amounts between 0.05 and 10% by weight, based on the total weight of the agent. 7. Agent according to one or more of claims 4 to 6f, characterized in that there are also other 'sun-filtering agents which are water- or fat-soluble and which are resistant to UV radiation B. -A- show a filtering effect contains. 8. Process for the protection of cosmetic agents which contain components sensitive to UV radiation, characterized in that at least one of the in claim 1 brings in defined connections. 9. A method for protecting the skin against UV radiation A, characterized in that one on the skin at least one of those defined in claim 1 Compounds in an acceptable cosmetic environment, which ensures an even distribution on the skin.