DE19746654A1 - Use of 4,4-di:aryl-butadiene derivatives as photostable UV filter compounds - Google Patents

Abstract

The use of 4,4-diaryl-butadiene derivatives of formula (I), in which the diene system has Z,Z-, Z,E-, E,Z- or Z,Z-configuration (or a mixture of these), is claimed as photostable ultraviolet (UV) stabilisers in cosmetic or pharmaceutical preparations for protecting human skin against sunlight, (I) optionally being used in combination with known UV absorbers. R1,R2 = H; 1-20C alkyl, 2-10C alkenyl, 3-10C cycloalkyl, 3-10C cycloalkenyl, 1-12C alkoxy, 1-20C alkoxycarbonyl, mono- or di-(1-12C alkyl)-amino, aryl or heteroaryl (all optionally substituted); or water-solubilising substituents selected from carboxylate, sulphonate and ammonium; R3 = H or (all optionally substituted) COOR5, COR5, CONR5R6, CN, SO2R5, SO2OR5, P(O)(OR7)(OR8), 1-20C alkyl, 2-10C alkenyl, 3-10C cycloalkyl, 7-10C bicycloalkyl, 3-10C cycloalkenyl, 7-10C bicycloalkenyl, aryl or heteroaryl; R4 = as R3 but not H; R5-R8 = H or (all optionally substituted) 1-20C alkyl, 2-10C alkenyl, 3-10C cycloalkyl, 7-10C bicycloalkyl, 3-10C cycloalkenyl, 7-10C bicycloalkenyl, aryl or heteroaryl; or groups R3-R8 can together complete a 5- or 6-membered ring (optionally further fused). Also claimed are : (i) the use of (I) as photostable UV-A filters; (ii) the use of (I) as UV stabilisers in cosmetic and pharmaceutical compositions; (iii) cosmetic or pharmaceutical compositions for protecting the human epidermis or hair against UV light in the 280-400 nm region, comprising (I) and optionally known UV absorbers in a suitable carrier; (iv) (I) for use as medicament; and (v) pharmaceutical preparations containing (I).

Description

The invention relates to the use of 4,4-diarylbutadienes as photostable UV filters in cosmetic and pharmaceutical Preparations for the protection of the human epidermis or human Liche hair against UV radiation, especially in the range from 320 to 400 nm.

Used in cosmetic and pharmaceutical preparations th light stabilizers have the task of damaging influences to prevent or prevent sunlight from reaching human skin at least to reduce their effects. In addition, these serve Light stabilizers but also the protection of other ingredients Destruction or degradation by UV radiation. In hair cosmetic Formulations are said to cause damage to the keratin fiber UV rays are reduced.

The sunlight reaching the surface of the earth has a share UV-B (280 to 320 nm) and UV-A radiation (<320 nm), wel surface directly adjoins the area of visible light eat. The influence on human skin is special Noticeable in UV-B radiation through sunburn. Dementspre Accordingly, the industry offers a larger number of substances which absorb UV-B radiation and thus sunburn impede.

Now dermatological studies have shown that too UV-A radiation can cause skin damage and allergies can cause, for example, the keratin or elastin ge is damaged. This creates elasticity and water storage reduced capacity of the skin, d. H. the skin is less melted dig and tends to wrinkle. The strikingly high level of skin cancer frequency in areas of strong sunlight shows that of Damage to the genetic information in the cells can also be detected Sunlight, especially caused by UV-A radiation. All these findings therefore make development more efficient Filter substances appear necessary for the UV-A range.

There is a growing need for sunscreens for kosme table and pharmaceutical preparations, mainly used as UV-A filters can serve and their absorption maxima therefore in the Be should range from approx. 320 to 380 nm. To be able to to achieve the desired effect in the smallest possible amount, such light stabilizers should also have a highly specifi have cal extinction. In addition, light stabilizers must be used for cosmetic preparations have a variety of other requirements meet, for example good solubility in cosmetic oils, high stability of the emulsions made with them, toxicolo gical harmlessness as well as low inherent odor and low Inherent color.

Another requirement that light stabilizers must meet is is sufficient photostability. But this is with the up not available from UV-A absorbing sunscreens or insufficiently guaranteed.

In French patent specification No. 2 440 933 this is 4- (1,1-Dimethylethyl) -4'-methoxydibenzoylmethane as a UV-A filter described. It is suggested to use this special UV-A-Fil ter, which is available from GIVAUDAN under the name "PAR- SOL 1789 "is sold to be combined with various UV-B filters kidneys to absorb the total UV rays with a wavelength of 280 absorb up to 380 nm.

This UV-A filter is, however, when used alone or in combination tion is used with UV-B filters, not photochemically resistant dig enough to provide lasting skin protection during one to ensure prolonged sunbathing, resulting in repeated applications gen at regular and short intervals when using ei effective protection of the skin against all UV rays want to aim.

Therefore, according to EP-A-0 514 491, the insufficient photo stable UV-A filter through the addition of 2-cyan-3,3-diphenyla Acrylic acid esters are stabilized, even in the UV-B range serve as a filter.

Furthermore, it has already been proposed according to EP-A-0 251 398, Chromophores absorbing UV-A and UV-B radiation through a link to unite a molecule. This has the disadvantage that one on the other hand, there is no free combination of UV-A and UV-B filters in the cosmetic preparation is more possible and that difficulties in the chemical linkage of the chromophores only certain com allow binations.

No. 4,950,467 describes the use of 2,4-pentadienoic acid derivatives as UV absorbers in cosmetic preparations. The one in this Patent preferred monoaryl-substituted compound mentioned Applications also have the disadvantage that they do not have enough pho are extremely stable.

The object was therefore to find light stabilizers for cosmetic and to propose pharmaceutical purposes that are in the UV-A range absorb high absorbance, which are photostable, a low one Own color d. H. have a sharp band structure and depending on Substituent are soluble in oil or water.

This object was achieved according to the invention by using 4,4-diarylbutadienes of the formula I.

in which the diene system in the Z, Z; Z, E; E, Z or E, E configuration or a mixture thereof is present and in which the variables have the following meanings:
R ¹ and R ² independently of one another are hydrogen, C ₁ -C ₂₀ -alkyl, C ₂ -C ₁₀ -alkenyl, C ₃ -C ₁₀ -cycloalkyl, C ₃ -C ₁₀ -cycloalkenyl, C ₁ -C ₁₂ -alkoxy, C ₁ -C ₂₀ alkoxycarbonyl, C ₁ -C ₁₂ alkylamino, C ₁ -C ₁₂ dialkylamino, aryl, heteroaryl, optionally substituted, water-solubilizing substituents selected from the group consisting of carboxylate, sulfonate or ammonium radicals;
R ³ hydrogen, COOR ⁵ , COR ⁵ , CONR ⁵ R ⁶ , CN, O = S (-R ⁵ ) = O, O = S (-OR ⁵ ) = O, R ⁷ OP (-OR ⁸ ) = O, C ₁ -C ₂₀ alkyl, C ₂ -C ₁₀ alkenyl, C ₃ -C ₁₀ cycloalkyl, C ₇ -C ₁₀ bicloalkyl, C ₃ -C ₁₀ cycloalkenyl, C ₇ -C ₁₀ bicycloalkenyl, aryl , Heteroaryl, optionally substituted;
R ⁴ COOR ⁶ , COR ⁶ , CONR ⁵ R ⁶ , CN, O = S (-R ⁶ ) = O, O = S (-OR ⁶ ) = O, R ⁷ OP (-OR ⁸ ) = OC ₁ -C ₂₀ alkyl, C ₂ -C ₁₀ alkenyl, C ₃ -C ₁₀ cycloalkyl, C ₇ -C ₁₀ bicyclo alkyl, C ₃ -C ₁₀ cycloalkenyl, C ₇ -C ₁₀ bicycloalkenyl, aryl, heteroaryl, optionally substituted;
R ⁵ to R ⁸ independently of one another are hydrogen, C ₁ -C ₂₀ alkyl, C ₂ -C ₁₀ alkenyl, C ₃ -C ₁₀ cycloalkyl, C ₇ -C ₁₀ bicycloalkyl, C ₃ -C ₁₀ cycloalkenyl, C ₇ -C ₁₀ -bicycloalkenyl, aryl, heteroaryl, optionally substituted;
where the variables R ³ to R ⁸ with one another, in each case together with carbon atoms to which they are bonded, can together form a 5- or 6-ring, which can optionally be further fused,
as photostable UV filters in cosmetic and pharmaceutical preparations for protecting the human skin or human hair against sun rays, alone or together with compounds which are known per se for cosmetic and pharmaceutical preparations and absorb in the UV range.

As alkyl radicals R ¹ to R ⁸ , branched or unbranched C ₁ -C ₂₀ -alkyl chains, preferably methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, 2-methylpropyl, 1,1- Dimethyl ethyl, n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, n-hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2 -Methylpentyl, 3-methyl pentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1- Ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, 1-ethyl-2-methylpropyl, n-heptyl, n-octyl, n-nonyl , n-decyl, n-undecyl, n-dodecyl, n-tridecyl, n-tetradecyl, n-pentadecyl, n-hexadecyl, n-heptadecyl, n-octadecyl, n-nonadecyl or n-eico syl.

Alkenyl radicals R ¹ to R ⁸ are branched or unbranched C ₂ -C ₁₀ alkenyl chains, preferably vinyl, propenyl, isopropenyl, 1-butenyl, 2-butenyl, 1-pentenyl, 2-pentenyl, 2-methyl-1-butenyl, 2-methyl-2-butenyl, 3-methyl-1-butenyl, 1-hexenyl, 2-hexenyl, 1-heptenyl, 2-heptenyl, 1-octenyl or 2-octenyl.

Preferred cycloalkyl radicals for R ¹ to R ⁸ are branched or unbranched C ₃ -C ₁₀ cycloalkyl chains such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, 1-methylcyclopropyl, 1-ethylcyclopropyl, 1-propylcyclopropyl, 1-butylcyclopropyl, 1-butylcyclopropyl, , 1-methyl-1-butylcyclopropyl, 1,2-dimethylcyclypropyl, 1-methyl-2-ethylcyclopropyl, cyclooctyl, cyclononyl or cyclodecyl called.

Preferred cycloalkenyl radicals for R ¹ to R ⁸ are branched or unbranched, C ₃ -C ₁₀ cycloalkenyl chains with one or more double bonds, such as cyclopropenyl, cyclobutenyl, cyclopentene nyl, cyclopentadienyl, cyclohexenyl, 1,3-cyclohexadienyl, 1,4-cy clohexadienyl, cycloheptenyl, cycloheptatrienyl, cyclooctenyl, 1,5-cyclooctadienyl, cyclooctatetraenyl, cyclononenyl or cyclo decyl called.

The cycloalkenyl and cycloalkyl radicals can optionally with one or more, z. B. 1 to 3 radicals such as halogen z. B. fluorine, chlorine or bromine, cyano, nitro, amino, C ₁ -C ₄ -alkylamino, C ₁ -C ₄ -dialkylamino, hydroxy, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkoxy or other radicals be substituted or 1 to 3 heteroatoms such as sulfur, nitrogen, the free valences of _{which can be saturated by hydrogen or C 1} -C ₄ -alkyl or contain oxygen in the ring.

As bicycloalkyl or bicycloalkenyl radicals for R ³ to R ^{8 are} ge saturated or unsaturated C ₇ -C ₁₀ bicyclic ring systems, in particular special bicyclic terpenes such as pinane, pinene, bornane, camphor derivatives or adamantane.

Suitable alkoxy radicals for R ¹ and R ² are those with 1 to 12 carbon atoms, preferably with 1 to 8 carbon atoms.

Examples include:

Methoxy Ethoxy Isopropoxy n-propoxy 1-methylpropoxy n-butoxy n-pentoxy 2-methylpropoxy 3-methylbutoxy 1,1-dimethylpropoxy 2,2-dimethylpropoxy Hexoxy 1-methyl-1-ethylpropoxy Heptoxy Octoxy 2-ethylhexoxy

Alkoxycarbonyl radicals for R ¹ and R ² are, for. B. esters containing the above-mentioned alkoxy radicals or radicals of higher alcohols z. B. with up to 20 carbon atoms, such as iso-C ₁₅ alcohol.

Suitable mono- or dialkylamino ^{radicals for R 1} and R ² are those which contain alkyl radicals having 1 to 12 carbon atoms, such as. B. methyl, n-propyl, n-butyl, 2-methylpropyl, 1,1-dimethyl propyl, hexyl, heptyl, 2-ethylhexyl, isopropyl, 1-methylpro pyl, n- Pentyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-methyl-1-ethylpropyl and octyl.

Aryl is to be understood as meaning aromatic rings or ring systems with 6 to 18 carbon atoms in the ring system, for example phenyl or naphthyl, optionally with one or more radicals such as halogen, for. B. fluorine, chlorine or bromine, cyano, nitro, amino, C ₁ -C ₄ -alkylamino, C ₁ -C ₄ -dialkylamino, hydroxy, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkoxy or other radicals can be substituted. Any substituted phenyl, methoxyphenyl and naphthyl are preferred.

Heteroaryl radicals are advantageously simple or condensed based aromatic ring systems with one or more heteroaro matic 3- to 7-membered rings. As heteroatoms can be a or more nitrogen, sulfur and / or oxygen atoms in the Ring or ring system be included.

Hydrophilic, ie the water solubility of the compounds of the formula enabling radicals for R ¹ and R ² are z. B. carboxy and sulfo xyreste and especially their salts with any physiologically acceptable cations, such as the alkali salts or the trialkyl ammonium salts, such as tri- (hydroxyalkyl) ammonium salts or the 2-methylpropan-1-ol-2-ammonium salts. Ammonium, in particular alkylammonium, radicals with any physiologically acceptable anions are also suitable.

Those compounds of the formula I are preferred in which
R ¹ and R ² independently of one another are hydrogen, C ₁ -C ₁₂ -alkyl, C ₁ -C ₈ -alkoxy, C ₁ -C ₁₂ -alkylamino, C ₁ -C ₁₂ -dialkylamino, water-solubilizing substituents selected from the group consisting of from carboxylate, sulfonate or ammonium residues;
R ^{3 is} hydrogen, COOR ⁵ , COR ⁵ , CONR ⁵ R ⁶ , CN, C ₁ -C ₁₂ alkyl, C ₃ -C ₆ cycloalkyl, C ₇ -C ₁₀ bicycloalkyl, phenyl, naphthyl, thienyl, optionally substituted;
R ⁴ COOR ⁶ , COR ⁶ , CONR ⁵ R ⁶ , CN, C ₁ -C ₁₂ alkyl, C ₃ -C ₁₀ cycloalkyl, C ₇ -C ₁₀ bicycloalkyl, phenyl, naphthyl, thienyl, optionally substituted;
R ⁵ and R ⁶ independently of one another are hydrogen, C ₁ -C ₁₂ alkyl, C ₃ -C ₆ cycloalkyl, C ₇ -C ₁₀ bicycloalkyl, phenyl, naphthyl, optionally substituted,
means.

Particularly preferred C ₁ -C ₁₂ -alkyl radicals for R ¹ to R ⁶ are methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, n- Pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 2-ethylhexyl.

As cycloalkyl ^{radicals for R 3} to R ⁶ , branched or unbranched cyclopentyl and cyclohexyl are particularly preferred.

Particularly preferred mono- or dialkylamino radicals for R ¹ and R ² are methyl, ethyl, n-propyl, n-butyl, 2-methylpropyl, 1,1-dimethylpropyl, 2-ethylhexyl.

Particularly preferred bicycloalkyl radicals for R ³ to R ⁶ are cam pher derivatives.

The substituents R ¹ and R ² can each be bonded to the aromatic in the ortho, meta or para position. Particularly preferred are compounds of the formula I in which R ^{1 is the} same as R ² and both Re ste are in the para position.

The use of compounds of the formula I in which R ³ or R ^{4 may} not be H, CN, C ₁ -C ₂₀ -alkyl, C ₂ -C ₁₀ -alkenyl, aryl, heteroaryl, optionally substituted, is also particularly preferred, when R ⁴ or R ^{3 is} COOR ⁵ or COOR ⁶ .

Compounds of the formula I are very particularly preferred
R ¹ and R ² independently of one another are hydrogen, C ₁ -C ₁₂ -alkyl, C ₁ -C ₈ -alkoxy, water-solubilizing substituents selected from the group consisting of carboxylate, sulfonate or ammonium radicals;
R ^{3 is} hydrogen, COOR ⁵ , COR ⁵ , CONR ⁵ R ⁶ , CN, C ₃ -C ₆ cycloalkyl, C ₇ -C ₁₀ bicycloalkyl;
R ⁴ COOR ⁶ , COR ⁶ , CONR ⁵ R ⁶ , CN, C ₃ -C ₆ cycloalkyl, C ₇ -C ₁₀ bicycloalkyl,
where R ³ or R ^{4 may} not be COOR ⁵ or COOR ⁶ when R ^{4 is} CN or R ^{3 is} hydrogen or CN;
R ⁵ and R ⁶ independently of one another are hydrogen, C ₁ -C ₁₂ alkyl, C ₃ -C ₆ cycloalkyl, C ₇ -C ₁₀ bicycloalkyl, phenyl, naphthyl, optionally substituted,
means.

Furthermore, compounds of the formula I have particular photostable properties in which the substituents R ¹ to R ^{4 are present} in the combination specified in Table 1:

Table 1

Likewise very particularly preferred are those compounds of the formula I which are particularly photostable and at the same time colorless, in which
R ¹ and R ² independently of one another are hydrogen, C ₁ -C ₁₂ -alkyl, C ₁ -C ₈ -alkoxy, water-solubilizing substituents selected from the group consisting of carboxylate, sulfonate or ammonium radicals;
R ³ COOR ⁵ , COR ⁵ , CONR ⁵ R ⁶ ;
R ⁴ COOR ⁶ , COR ⁶ , CONR ⁵ R ⁶ ;
R ⁵ and R ⁶ independently of one another are hydrogen, C ₁ -C ₁₂ alkyl, C ₃ -C ₆ cycloalkyl, C ₇ -C ₁₀ bicycloalkyl, phenyl, naphthyl, optionally substituted,
means.

The compounds of the formula I to be used according to the invention can be prepared according to the equation

be prepared by condensation, where R ¹ to R ^{4 have} the meaning given in claim 1 to.

For example, the reaction of β-phenylcinnamaldehyde results in Diethyl malonate is compound 1 in Tab. 2.

In the event that R ³ ≠ R ⁴ , the compounds according to the invention of the formula I can in principle in their various geometric isomers, ie with a Z, Z; Z, E; E, Z and / or E, E-configured diene system are present. The all-E and / or all-Z isomers are preferred as cosmetic light protection agents, the all-E isomers are very particularly preferred.

If R ³ = R ⁴ , the CC double bond between C-3 and C-4 (in the position adjacent to the diaryl system) can be in the E and / or Z configuration, preferably in the Z configuration.

The cosmetic and pharmaceutical products containing light stabilizers cal preparations are usually based on a Trä gers, which contains at least one oil phase. But they are also closed preparations on an aqueous basis only when using Verbin Applications with hydrophilic substituents are possible. Come accordingly Oils, oil-in-water and water-in-oil emulsions, creams and pa sten, lip protection stick masses or fat-free gels into consideration.

Such sunscreen preparations can accordingly be liquid, pasty in water or solid form, for example as water-in-oil creams, Oil-in-water creams and lotions, aerosol foam creams, Gels, oils, grease pencils, powders, sprays or alcohol-based loos options.

Common oil components in cosmetics are, for example, paraf fin oil, glyceryl stearate, isopropyl myristate, diisopropyl adipate, Cetylstearyl 2-ethylhexanoate, hydrogenated polyisobutene, Va seline, caprylic acid / capric acid triglycerides, microcrystalline Wax, lanolin and stearic acid.

Usual cosmetic auxiliaries that can be used as additives men are z. B. co-emulsifiers, fats and waxes, stabilizers agents, thickeners, biogenic agents, film formers, Fragrances, dyes, pearlescent agents, preservatives, Pigments, electrolytes (e.g. magnesium sulfate) and pH regulators. Known W / O and in addition are preferably used as co-emulsifiers also O / W emulsifiers such as polyglycerol esters, sorbitan esters or partially esterified glycerides. Typical examples of Fats are glycerides; as waxes are inter alia. Beeswax, paraffin wax or micro waxes, optionally in combination with hydro phile waxes. Metal salts can be used as stabilizers Fatty acids such as B. magnesium, aluminum and / or zinc stea council are used. Suitable thickeners are at for example crosslinked polyacrylic acids and their derivatives, poly saccharides, in particular xanthan gum, guar guar, agar agar, algi nate and tylose, carboxymethyl cellulose and hydroxyethyl cellulose loose, also fatty alcohols, monoglycerides and fatty acids, polycry late, polyvinyl alcohol and polyvinyl pyrrolidone. Under biogenic Active ingredients are, for example, plant extracts, protein hydrolytes To understand sate and vitamin complexes. Common film formers are for example hydrocolloids such as chitosan, microcrystalline Chitosan or quaternized chitosan, polyvinylpyrrolidone, vinyl pyrrolidone-vinyl acetate copolymers, polymers of acrylic acid series, quaternary cellulose derivatives and similar compounds. Formaldehyde, for example, is suitable as a preservative solution, p-hydroxybenzoate or sorbic acid. As a pearlescent agent for example glycol distearic acid esters such as ethylene glycol cold distearate, but also fatty acids and fatty acid monoglycol esters into consideration. As dyes, those used for cosmetic purposes can be used Appropriate and approved substances are used as they are for example in the publication "Cosmetic colorants" Dye Coordination of the German Research Foundation, publ published by Verlag Chemie, Weinheim, 1984, compiled are. These dyes are usually used in concentrations of 0.001 to 0.1 wt .-%, based on the total mixture, incorporated puts.

The total amount of auxiliaries and additives can be 1 to 80, before preferably 6 to 40% by weight and the non-aqueous portion ("Aktiv substance ") 20 to 80, preferably 30 to 70 wt .-% - based on the means - amount. The preparation of the means can in itself known way, d. H. for example by hot, cold, Hot-hot / cold or PIT emulsification take place. This is it a purely mechanical process, a chemical reaction fin det does not take place.

Finally, others known per se in the UV-A range can be used Sorbing substances are also used, provided they are in the Ge complete system of the combination to be used according to the invention UV-B and UV-A filters are stable.

The present invention also relates to cosmetic products and pharmaceutical preparations containing 0.1 to 10% by weight preferably 1 to 7 wt .-%, based on the total amount of kos metallic and pharmaceutical preparation, one or more of the Compounds of the formula I together with per se for cosmetic and pharmaceutical preparations known in the UV-B range Sorbent compounds contain as light stabilizers, wherein the compounds of the formula I usually in a smaller amount can be used as the UV-B absorbing compounds.

Most of the sunscreens in the to protect the Cosmetic and pharmaceutical products used for human epidermis preparations consists of compounds that absorb UV light Absorb UV-B range d. H. in the range from 280 to 320 nm. At for example, the proportion is to be used according to the invention the UV-A absorber 10 to 90% by weight, preferably 20 to 50% by weight, based on the total amount of UV-B and UV-A absorbing sub punch.

As UV filter substances, which in combination with the erfindungsge are used according to compounds of the formula I to be used, Any UV-A and UV-B filter substances can be used.

Examples include:

Finally, micronized pigments such as titanium dioxide and To mention zinc oxide.

To protect human hair from UV rays, the inventions can proper light protection agent of the formula I in shampoos, lotions, Gels, hairsprays, aerosol foam creams or emulsions in con concentrations of 0.1 to 10% by weight, preferably 1 to 7% by weight be incorporated. The respective formulations can thereby i.a. used for washing, coloring and styling hair will.

The compounds to be used according to the invention are distinguished usually due to a particularly high absorption capacity in the bed rich in UV-A radiation with a sharp band structure. Further they are well soluble in cosmetic oils and can be easily incorporated into cosmetic formulations. The ones with the Compounds I produced emulsions stand out particularly due to their high stability, the connections I themselves due to their high photostability, and the preparations made with I through their pleasant feeling on the skin.

The UV filter effect of the compounds according to the invention of For mel I can also be used to stabilize active ingredients and auxiliaries in cosmetic and pharmaceutical formulations who exploited the.

The invention also relates to the compounds of the formula I for use as medicaments and pharmaceutical agents for preventive treatment of inflammation and allergies of the skin as well as for the prevention of certain types of skin cancers, which have an effective same amount of at least one compound of formula I as active ingredient contain.

The pharmaceutical agent according to the invention can be oral or to administered pisch. For oral administration that is pharmaceutical agents in the form of i.a. Lozenges, gelatine caps sugar, coated tablets, as a syrup, solution, emulsion or suspension.

The topical application of the pharmaceutical agent takes place at for example as an ointment, cream, gel, spray, solution or lotion.

Examples I. Manufacture example 1 Manufacturing instructions for the compound No. 1 in Table 2

0.1 mol of β-phenylcinnamaldehyde and 0.1 mol of diethyl malonate are dissolved in 100 ml of methanol, each with 1 ml of piperidine and ice added vinegar and heated to reflux for 5 h. Then with Diluted water and extracted with dichloromethane. The organic Phase is stirred up with activated charcoal. After filtering off the orga niche phase is dried over sodium sulfate and in vacuo constricted. The oily residue is recirculated from methanol / water installed. 12 g (33% of theory) of compound 1 are obtained Table 2 as colorless crystals. Purity: <99% (GC).

Compounds 2 to 6 in Table 2 are prepared analogous to example 1.

Example 2 Manufacturing instructions for the connection of No. 8 in Table 2

0.1 mol of camphor in 40 ml of xylene are mixed with 0.1 mol of KOH and heated to reflux. Then slowly one over 6 h A solution of 0.105 mol of β-phenylcinnamaldehyde in xylene was added dropwise.

After cooling to room temperature, water is added, which organic phase washed twice with water and then dried over sodium sulfate. After removing the solvent, the oily residue crystallized from methanol / water. Man he holds 22 g (64%) of colorless crystals of compound 19 of the table 1. Purity 99% (HPLC, isomer mixture).

Compound 7 of Table 2 is prepared by Um Settlement of β-phenylcinnamaldehyde with pinacolone as in Example 2.

Table 2

Example 3 Standardized method for determining photostability (Sun test)

A 5% strength by weight alcoholic solution of the light to be tested protective agent is applied to the Milling of a glass plate applied. Through the estate The solution is evenly distributed over the alcohol roughened glass surface. The applied amount corresponds to Amount of sunscreen used in sunscreens to achieve a medium sun protection factor is required. During the exam 4 glass plates are irradiated in each case. The evaporation time and the Irradiation is 30 minutes each. The glass slides are weh rend of irradiation through a water cooling system, which is located on the ground of the sun test device is slightly cooled. The temperature inside half of the Suntest device is 40 ° C during irradiation. After the samples have been irradiated, they are washed with ethanol a dark 50 ml volumetric flask and washed with the photometer measured. The blank samples are also placed on glass slides wear and evaporated for 30 minutes at room temperature. Like that on their samples are washed off with ethanol and made up to 100 ml diluted and measured.

Comparative tests with regard to photostability

General manufacturing instructions for the manufacture of emulsions for cosmetic purposes

All oil-soluble components are in a stirred tank Heated to 85 ° C. When all components are melted or as If the liquid phase is present, the water phase is homogenized incorporated. The emulsion is removed to approx. 40 ° C. with stirring cools, perfumes, homogenizes and then with constant stirring cooled to 25 ° C.

Preparations Example 4 Composition for lip care

Mass content
(Wt%)

ad 100 Eucerinum anhydricum
10.00 glycerin
10.00 titanium dioxide
5.00 Compound No. 1 of Table 2
8.00 octyl methoxycinnamate
5.00 zinc oxide
4.00 castor oil
4.00 Pentaerythrithil stearate / caprate / caprylate adipate
3.00 glyceryl stearate SE
2.00 beeswax
2.00 microcrystalline wax
2.00 Quaternium-18 bentonite
1.50 PEG-45 / dodecyl glycol copolymer

Example 5 Composition for lip care

Mass content
(Wt%)

ad 100 Eucerinum anhydricum
10.00 glycerin
10.00 titanium dioxide
5.00 Compound No. 1 of Table 2
8.00 octyl methoxycinnamate
5.00 zinc oxide
4.00 castor oil
4.00 Pentaerythrithil stearate / caprate / caprylate adipate
3.00 glyceryl stearate SE
2.00 beeswax
2.00 microcrystalline wax
2.00 Quaternium-18 bentonite
1.50 PEG-45 / dodecyl glycol copolymer

Example 6 Composition for sunblock with micropigments

Mass content
(Wt%)

ad 100 water
10.00 octyl methoxycinnamate
6.00 PEG-7 Hydrogenated Castor Oil
6.00 titanium dioxide
5.00 Compound No. 1 of Table 2
5.00 mineral oil
5.00 isoamyl p-methoxycinnamate
5.00 propylene glycol
3.00 jojoba oil
3.00 4-methylbenzylidene camphor
2.00 PEG-45 / dodecyl glycol copolymer
1.00 dimethicone
0.50 PEG-40-Hydrogenated Castor 01
0.50 tocopheryl acetate
0.50 phenoxyethanol
0.20 EDTA

Example 7 Composition for sunblock with micropigments

Mass content
(Wt%)

ad 100 water
10.00 octyl methoxycinnamate
6.00 PEG-7 Hydrogenated Castor Oil
6.00 titanium dioxide
5.00 Compound No. 1 of Table 2
5.00 mineral oil
5.00 isoamyl p-methoxycinnamate
5.00 propylene glycol
3.00 jojoba oil
3.00 jojoba oil
2.00 4-methylbenzylidene camphor
1.00 PEG-45 / Dodecyl Glycol Copolymer
0.50 dimethicone
0.50 PEG-40 Hydrogenated Castor Oil
0.50 tocopheryl acetate
0.20 phenoxyethanol
0.20 EDTA

Example 8 Fat-free gel

Mass content
(Wt%)

ad 100 water
8.00 octyl methoxycinnamate
7.00 titanium dioxide
5.00 Compound No. 1 of Table 2
5.00 glycerin
5.00 PEG-25 PABA
1.00 PEG-25 PABA
0.40 4-methylbenzylidene camphor
0.30 Acrylate C10-C30 Alkyl Acrylate Crosspolymer
0.25 imidazolidinyl urea
0.25 hydroxyethyl cellulose
0.20 sodium methyl paraben
0.15 disodium EDTA
0.15 fragrance
0.15 sodium propyl paraben
0.10 sodium hydroxide

Example 9 Fat-free gel

Mass content
(Wt%)

ad 100 water
8.00 octyl methoxycinnamate
7.00 titanium dioxide
5.00 Compound No. 1 of Table 2
5.00 glycerin
5.00 PEG-25 PABA
1.00 4-methylbenzylidene camphor
0.40 Acrylate C10-C30 alkyl acrylate cross polymer
0.30 imidazolidinyl urea
0.25 hydroxyethyl cellulose
0.25 sodium methyl paraben
0.20 disodium EDTA
0.15 fragrance
0.15 sodium propyl paraben
0.10 sodium hydroxide

Example 10 Sunscreen (SPF 20)

Mass content
(Wt%)

ad 100 water
8.00 octyl methoxycinnamate
8.00 titanium dioxide
6.00 PEG-7 Hydrogenated Castor Oil
5.00 Compound No. 1 of Table 2
6.00 mineral oil
5.00 zinc oxide
5.00 isopropyl palmitate
5.00 imidazolidinyl urea
3.00 jojoba oil
2.00 PEG-45 / dodecyl glycol copolymer
1.00 4-methylbenzylidene camphor
0.60 magnesium stearate
0.50 tocopheryl acetate
0.25 methyl paraben
0.20 disodium EDTA
0.15 propyl paraben

Example 11 Sunscreen (SPF 20)

Mass content
(Wt%)

ad 100 water
8.00 octyl methoxycinnamate
8.00 titanium dioxide
6.00 PEG-7 Hydrogenated Castor Oil
5.00 Compound No. 1 of Table 2
6.00 mineral oil
5.00 zinc oxide
5.00 isopropyl palmitate
5.00 imidazolidinyl urea
3.00 jojoba oil
2.00 PEG-45 / dodecyl glycol copolymer
1.00 4-methylbenzylidene camphor
0.60 magnesium stearate
0.50 tocopheryl acetate
0.25 methyl paraben
0.20 disodium EDTA
0.15 propyl paraben

Example 12 Waterproof sunscreen

Mass content
(Wt%)

ad 100 water
8.00 octyl methoxycinnamate
5.00 PEG-7 Hydrogenated Castor Oil
5.00 Propylene Glycol
4.00 isopropyl palmitate
4.00 Caprylic / Capric Triglyceride
5.00 Compound No. 1 of Table 2
4.00 glycerin
3.00 jojoba oil
2.00 4-methylbenzylidene camphor
2.00 titanium dioxide
1.50 PEG-45 / dodecyl glycol copolymer
1.50 dimethicone
0.70 magnesium sulfate
0.50 magnesium stearate
0.15 fragrance

Example 13 Waterproof sunscreen

Mass content
(Wt%)

ad 100 water
8.00 octyl methoxycinnamate
5.00 PEG-7 Hydrogenated Castor Oil
5.00 Propylene Glycol
4.00 isopropyl palmitate
4.00 Caprylic / Capric Triglyceride
5.00 Compound No. 1 of Table 2
4.00 glycerin
3.00 jojoba oil
2.00 4-methylbenzylidene camphor
2.00 titanium dioxide
1.50 PEG-45 / dodecyl glycol copolymer
1.50 dimethicone
0.70 magnesium sulfate
0.50 magnesium stearate
0.15 Fragance

Example 14 Sun milk (SPF 6)

Mass content
(Wt%)

ad 100 water
10.00 mineral oil
6.00 PEG-7 Hydrogenated Castor Oil
5.00 isopropyl palmitate
3.50 octyl methoxycinnamate
5.00 Compound No. 1 of Table 2
3.00 Caprylic / Capric Triglyceride
3.00 jojoba oil
2.00 PEG-45 / dodecyl glycol copolymer
0.70 magnesium sulfate
0.60 magnesium stearate
0.50 tocopheryl acetate
0.30 glycerin
0.25 methyl paraben
0.15 propyl paraben
0.05 tocopherol

Example 15 Sun milk (SPF 6)

Mass content
(Wt%)

ad 100 water
10.00 mineral oil
6.00 PEG-7 Hydrogenated Castor Oil
5.00 isopropyl palmitate
3.50 octyl methoxycinnamate
5.00 Compound No. 1 of Table 2
3.00 Caprylic / Capric Triglyceride
3.00 jojoba oil
2.00 PEG-45 / dodecyl glycol copolymer
0.70 magnesium sulfate
0.60 magnesium stearate
0.50 tocopheryl acetate
0.30 glycerin
0.25 methyl paraben
0.15 propyl paraben
0.05 tocopherol

Example 16 Waterproof sunscreen

Mass content
(Wt%)

ad 100 water
8.00 octyl methoxycinnamate
5.00 PEG-7 Hydrogenated Castor Oil
5.00 Propylene Glycol
4.00 isopropyl palmitate
4.00 Caprylic / Capric Triglyceride
5.00 Compound No. 1 of Table 2
4.00 glycerin
3.00 jojoba oil
2.00 4-methylbenzylidene camphor
2.00 titanium dioxide
1.50 PEG-45 / dodecyl glycol copolymer
1.50 dimethicone
0.70 magnesium sulfate
0.50 magnesium stearate
0.15 Fragance

Example 17 Suntan lotion

Mass content
(Wt%)

ad 100 water
10.00 mineral oil
6.00 PEG-7 Hydrogenated Castor Oil
5.00 isopropyl palmitate
3.50 octyl methoxycinnamate
5.00 Compound No. 1 of Table 2
3.00 Caprylic / Capric Triglyceride
3.00 jojoba oil
2.00 PEG-45 / dodecyl glycol copolymer
0.70 magnesium sulfate
0.60 magnesium stearate
0.50 tocopheryl acetate
0.30 glycerin
0.25 methyl paraben
0.15 propyl paraben
0.05 tocopherol

Claims (8)

1. Use of 4,4-diarylbutadienes of the formula I,
in which the diene system in the Z, Z; Z, E; E, Z or E, E configuration or a mixture thereof is available and in which the variables have the following meanings:
R ¹ and R ² independently of one another are hydrogen, C ₁ -C ₂₀ -alkyl, C ₂ -C ₁₀ -alkenyl, C ₃ -C ₁₀ -cycloalkyl, C ₃ -C ₁₀ -cycloalkenyl, C ₁ -C ₁₂ -alkoxy, C ₁ -C ₂₀ alkoxycarbonyl, C ₁ -C ₁₂ alkylamino, C ₁ -C ₁₂ dialkylamino, aryl, heteroaryl, optionally substituted, water-solubilizing substituents selected from the group consisting of carboxylate, sulfonate or ammonium radicals;
R ³ hydrogen, COOR ⁵ , COR ⁵ , CONR ⁵ R ⁶ , CN, O = S (-R ⁵ ) = O, O = S (-OR ⁵ ) = O, R ⁷ OP (-OR ⁸ ) = O, C ₁ -C ₂₀ alkyl, C ₂ -C ₁₀ alkenyl, C ₃ -C ₁₀ cycloalkyl, C ₇ -C ₁₀ bicycloalkyl, C ₃ -C ₁₀ cycloalkenyl, C ₇ -C ₁₀ bicycloalkenyl, aryl , Heteroaryl, optionally substituted;
R ⁴ COOR ⁶ , COR ⁶ , CONR ⁵ R ⁶ , CN, O = S (-R ⁶ ) = O, O = S (-OR ⁶ ) = O, R ⁷ OP (-OR ⁸ ) = O, C ₁ -C ₂₀ -alkyl, C ₂ -C ₁₀ -alkenyl, C ₃ -C ₁₀ -cycloalkyl, C ₇ -C ₁₀ -bi cycloalkyl, C ₃ -C ₁₀ -cycloalkenyl, C ₇ -C ₁₀ -bicycloalkenyl, aryl, heteroaryl , optionally substituted;
R ⁵ to R ⁸ independently of one another are hydrogen, C ₁ -C ₂₀ alkyl, C ₂ -C ₁₀ alkenyl, C ₃ -C ₁₀ cycloalkyl, C ₇ -C ₁₀ bicycloalkyl, C ₃ -C ₁₀ cycloalkenyl, C ₇ -C ₁₀ -Bicycloalkenyl, aryl, Heteroa ryl, optionally substituted;
where the variables R ³ to R ⁸ with one another, in each case together with the carbon atoms to which they are bound, can together form a 5- or 6-ring, which can optionally be further fused,
as photostable UV filters in cosmetic and pharmaceutical preparations for protecting the human skin or human hair against sun rays, alone or together with compounds that are known per se for cosmetic and pharmaceutical preparations and absorb in the UV range. 2. Use of compounds of formula I according to claim 1 as photostable UV-A filters. 3. Use of compounds of the formula I according to claims chen 1 and 2 as UV stabilizers in cosmetic and pharmaceuticals zeutic formulations. 4. Use of compounds of the formula I according to claims 1 to 3, where the substituents have the following meanings:
R ¹ and R ² independently of one another are hydrogen, C ₁ -C ₁₂ -alkyl, C ₁ -C ₈ -alkoxy, C ₁ -C ₁₂ -alkylamino, C ₁ -C ₁₂ -dialkylamino, water-solubilizing substituents selected from the group consisting of residues from carboxylate, sulfonate or ammonium;
R ^{3 is} hydrogen, COOR ⁵ , COR ⁵ , CONR ⁵ R ⁶ , CN, C ₁ -C ₁₂ alkyl, C ₃ -C ₆ cycloalkyl, C ₇ -C ₁₀ bicycloalkyl, phenyl, naphthyl, thienyl, optionally substituted;
R ⁴ COOR ⁶ , COR ⁶ , CONR ⁵ R ⁶ , CN, C ₁ -C ₁₂ alkyl, C ₃ -C ₆ cycloalkyl, C ₇ -C ₁₀ bicycloalkyl, phenyl, naphthyl, thienyl, optionally substituted;
R ⁵ and R ⁶ independently of one another are hydrogen, C ₁ -C ₁₂ alkyl, C ₃ -C ₆ cycloalkyl, C ₇ -C ₁₀ bicycloalkyl, phenyl, naphthyl, optionally substituted. 5. Cosmetic and pharmaceutical preparations containing light stabilizers for protecting the human epidermis or human hair against UV light in the range from 280 to 400 nm, characterized in that they are in a cosmetically and pharmaceutically suitable carrier, alone or together with per se for cosmetic and pharmaceutical preparations known in the UV range absorbing compounds, effective as photo-stable UV filters amounts of compounds of the formula I
contain, in which the variables have the meaning according to claim 1. 6. Cosmetic and pharmaceutical products containing light stabilizers Preparations according to claim 5, containing as UV-A filter Compounds of the formula I in which the variables have the meaning according to claim 4 have. 7. Compounds of the formula I for use as medicaments. 8. Pharmaceutical preparation, characterized in that it an effective amount of at least one of the compounds of the For mel I according to claim 1 contains.