EP2229169A1

EP2229169A1 - Preparation containing chromane-2-one derivatives

Info

Publication number: EP2229169A1
Application number: EP08870808A
Authority: EP
Inventors: Teresa Mujica-Fernaud; Sylvia EISENBERG
Original assignee: Merck Patent GmbH
Current assignee: Merck Patent GmbH
Priority date: 2008-01-17
Filing date: 2008-12-12
Publication date: 2010-09-22
Also published as: US20100291009A1; WO2009089880A1; JP2011509954A; CN101917989A

Abstract

The invention relates to preparations containing at least one compound of the formula (I), wherein the substituents R1 through R4 have a meaning disclosed in Claim 1, and to the salts and solvates thereof, and to the use thereof, and to selected compounds of the formula (I).

Description

Preparation containing chroman-2-one derivatives

The invention relates to a preparation containing at least one compound of the formula I.

, in which

R ¹ to R ^{3 are} each independently H, A, Y, OCOA or NHCOA,

R ^{4 is} H, A, Y \ OCOA or NHCOA,

R ² R ³ or R ¹ R ⁴ each independently together are methylenedioxy or ethylenedioxy,

Each independently of one another is a saturated or unsaturated, linear, branched or cyclic alkyl group having 1 to 18 C atoms, which is also denoted by OH, O-alkyl, CO-alkyl, COOH, COO-alkyl, NH ₂ ,

NH-alkyl, N (alkyl) ₂ , NHCO-alkyl, CONH ₂ , CONH-alkyl, sulfonate,

OSi (alkyl) ₃ , F, Cl or Br may be substituted,

Y is OH, OA, COA, COOH, COOA, NH ₂ , NHA, NA ₂ , NHCOA, CONH ₂ ,

CONHA, sulfonate, silyloxy, F, Cl, or Br means

Y ¹ OA, COA, COOH, COOA, NH ₂ , NHA, NA ₂ , NHCOA, CONH ₂ , CONHA, sulfonate, OSi (A) ₃ , F, Cl, or Br means and

Alkyl is a saturated or unsaturated, linear, branched or cyclic

Alkyl group having 1 to 18 carbon atoms, or their salts or solvates and their use and selected

Compounds of the formula I.

The chroman-2-ones of the formula I are in particular tyrosinase inhibitors, suitable for whitening human skin or for prophylaxis and / or Treatment of pigment disorders such as hyperpigmentation, freckles, age spots, sun spots and environmental aging.

Skin and hair color are dependent on the content, size and type of

Melanin (a nitrogenous dark dye) which is produced from melanocytes, the cells capable of melanin formation. Based on tyrosine and the help of various melanocyte-specific enzymes such as tyrosinase or tyrosinase-related proteins, melanin is produced within the melanosomes, with subsequent transformation of the melanosomes into keratinocytes.

Although the melanin in the skin is a suitable protection against UV radiation, darker or over-pigmented skin, as already mentioned, can affect the beauty and lead to serious aesthetic problems. Hyperpigmented skin conditions or lesions contain melasma (also called chloasma), i. irregularly shaped yellowish-brown spots.

In general, pigment spots are differentiated between freckles (ephelides), lentigines, so-called senile warts (verrucae seborrhoicea) and hyperpigmentation (for example, chloasma or melasma), and very often the sun plays an important role here. Especially people with very light skin and reddish hair tend to have freckles. Hyperpigmentation (chloasma), on the other hand, is common in those women who routinely deliver estrogen to their bodies.

You can prevent it especially by regular sunscreen with a high SPF. Once it has happened, however, various options are available, such as lasers, dermabrasion or other electrosurgical procedures, as well as so-called bleaching creams to remove the unsightly age spots. The latter alternative (bleaching creams) has the advantage that it is much cheaper for the patient than the electrosurgical procedures.

A large number of skin-whitening compounds for the treatment of pigmentation marks are available on the market.

These include compounds such as kojic acid, arbutin, aloesin or rucinol, which inhibit melamine production in the skin. They delay the conversion of tyrosine into melanin by blocking the enzyme tyrosinase.

However, these compounds have a number of disadvantages, such as e.g. low depigmentation efficiency, side effects such as skin irritation or skin exfoliation, cell damage, low penetration of the skin, or poor shelf-life of the formulations. Therefore, there is a need for new skin brighteners with higher efficiency.

Therefore, it was an object of the present invention to provide new formulations containing active ingredients which have the ability to brighten the skin.

The compounds of the formula I are known in part.

Dadak et al, Collection of Czechoslovak Chemical Communications 1973, 38 (8), 2313-19 describes the reduction products of 6-geranyl-7-hydroxycoumarin, for example 6- (3,7-dimethyloctyl) -3,4-dihydro-7-hydroxy -2H-1-benzopyran-2-one.

FR2293191 describes chroman-2-one derivatives whose substituents R ¹ to R ^{3 are} OH, OCH ₃ , OC ₂ H ₅ , CH ₃ , C ₂ H ₅ , H or halogen, which are suitable for hair treatment. WO 2001/16108 describes 6-alkylamino-chroman-2-one compounds, in particular 3,4-dihydro-6- (bis-2,2,2-trifluoroethyl) amino-4-trifluoromethylcoumarin in Example 217 as androgen receptor agonist as substitutes for the hormone replacement therapy.

The compounds of the formula Ia, a partial formula of the formula I,

^ where

R ^{4 is} a linear or cyclic alkyl group having 4-18 carbon atoms and their salts and solvates are novel and also the subject of the invention. Surprisingly, it has now been found that compounds of the formula I, as described below, have excellent skin lightening properties. They prevent the synthesis of melanin, prevent melanin overproduction and are therefore used to treat

Pigment spots of all kinds suitable. 0

Similar compounds, i. 6-Hydroxy-chroman-2-one derivatives with additional dialkyl groups at C-4 of the chroman-2-one skeleton are described in JP 2003321463, which compounds prevent melanogenesis by the induction of intracellular glutathione synthesis $ and none show direct inhibition of tyrosinase activity.

A first subject of the present invention is therefore a preparation containing at least one compound of formula I, 0

in which

R ¹ to R ^{3 are} each independently H, A, Y, OCOA or NHCOA,

R ^{4 is} H, A, Y ¹ , OCOA or NHCOA,

NH-alkyl, N (alkyl) ₂ , NHCO-alkyl, CONH ₂ , CONH-alkyl, sulfonate,

OSi (alkyl) ₃ , F, Cl or Br may be substituted,

Y is OH, OA, COA, COOH, COOA, NH ₂ , NHA, NA ₂ , NHCOA, CONH ₂ ,

CONHA, sulfonate, silyloxy, F, Cl, or Br means

Alkyl is a saturated or unsaturated, linear, branched or cyclic

Alkyl group having 1 to 18 carbon atoms, or their salts or solvates.

Solvates of the compounds of the formula I or Ia are understood to mean additions of inert solvent molecules to the compounds of the formula I or Ia which are formed on the basis of their mutual attraction. Solvates are, for example, mono- or dihydrate or addition compounds with alcohols, for example with methanol or ethanol. If the compounds of the formula I or Ia have at least one chiral center, they can occur in several stereoisomeric forms. All of these forms (eg, D and L forms) and their mixtures (eg, the DL forms) are included in the formula.

The radical R ² in formula I corresponds in a preferred embodiment to OH.

The radical R ⁴ in formula I corresponds in a preferred embodiment to H or A.

The radical R ³ in formula I corresponds in a preferred embodiment H.

In a particularly preferred embodiment, the at least one compound of the formula I is a compound of the formula Ia

wherein R ^{4 represents} a linear or cyclic alkyl group having 4-18 C atoms or one of their salts or solvates.

In the formulas I or Ia, A and alkyl each independently represent a saturated or unsaturated linear, branched or cyclic alkyl group, for example methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl or tert-butyl, furthermore also pentyl, 1-, 2- or 3-methylbutyl, 1, 1-, 1, 2- or 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1-, 2-, 3- or 4-methylpentyl, 1, 1-, 1, 2-, 1, 3-, 2,2-, 2,3- or 3,3-dimethylbutyl, 1- or 2-ethylbutyl, 1-ethyl-1-methylpropyl, 1-ethyl-2- methylpropyl, 1, 1, 2- or 1, 2,2-trimethylpropyl or alkyl groups and their isomers of Molar formulas C7H ₁₅ to C ₁₈ H ₃₇ , Alkenyigrupen or alkynyl groups having 1 to 18 carbon atoms, preferably, ethenyl, propenyl, butenyl, ethynyl, propynyl or butynyl or cycloalkyl having 3 to 9 carbon atoms, preferably cyclopentyl, cyclohexyl or cyclohepty! or cycloalkenyl having 5 to 9 C atoms, preferably cyclopentenyl, cyclohexenyl or cycloheptenyl.

A may optionally also be substituted, ie at least one H may, for example, be selected from a substituent selected from the group OH, O-alkyl CO-alkyl, COOH, CO-alkyl, NH ₂ , NH-alkyl, N (alkyl) ₂ , NHCO- Alkyl, CONH ₂ , CONH-alkyl, sulfonate, OSi (alkyl) ₃ , F, Cl or Br are substituted, wherein alkyl has one of the aforementioned or preferred meanings.

Alkyl particularly preferably denotes an alkyl group having 1 to 8 C atoms. Particularly preferred examples of the substituted A are hydroxyethyl, hydroxypropyl, aminoethyl, aminopropyl, alkoxyethyl (e.g.

Methoxyethyl, ethoxyethyl), alkoxypropyl (e.g. methoxypropyl, ethoxypropyl), carboxyalkyl (e.g. carboxymethyl, carboxyethyl), alkyloxycarbonylalkyl (e.g. methoxycarbonylmethyl, ethoxycarbonylmethyl, methoxycarbonylethyl, ethoxycarbonylethyl) or acylalkyl (e.g. acetylethyl).

R ⁴ in formula Ia is preferably a linear or cyclic alkyl group having 4-18 C atoms. R ⁴ in formula Ia particularly preferably represents butyl, hexyl, octyl, cyclohexyl, dodecyl, very particularly preferably hexyl.

Further preferred combinations of substituents are disclosed in the claims.

Particularly preferred compounds of the formula I or Ia are 6-hexyl-7-hydroxychroman-2-one, 6-ethyl-7-hydroxychroman-2-one, 7-hydroxychroman-2-one, 7-hydroxy-5-methyl-chroman-2-one,

5,7-dihydroxy-chroman-2-one,

6-butyl-7-hydroxychroman-2-one, β-cyclohexyl-hydroxychromanone, β-dodecyl-hydroxychromanone,

6-tert-octyl-7-hydroxychroman-2-one and its salts and solvates.

A special group of preferred compounds are the substances 6

Hexyl-7-hydroxychroman-2-one, 6-ethyl-7-hydroxychroman-2-one and 7-hydroxychroman-2-one. Most preferably, compound 6 is

Hexyl-7-hydroxy-chroman-2-one.

The compounds of the formula I and also the starting materials for their preparation are otherwise prepared by methods known per se, for example by condensation of hydroxy-substituted benzene with carboxylic acid derivatives (for example Synthesis, 2003, 1, 27-29).

However, another object of the invention is also a process for the preparation of compounds of formulas Ia and their salts and solvates, characterized in that

(a) a compound of formula IIa

wherein R ^{4 is} a previously stated or preferred

Meaning, implements with acrylic acid, and

(b) optionally converting a basic or acidic compound of formula Ia into one of its salts or solvates by treatment with an acid or base. The compounds of the formulas IIa are known compounds which are prepared by various methods or are in part also commercially available. For example, resorcinol or generally a hydroxyphenol with a

Carboxylic acid RCOOH are reacted in the presence of zinc chloride and the resulting condensate with zinc / amalgam / hydrochloric acid are reduced, analogous to Lille. J. Bitter et al., Inst. Slantsev 1969, 18, 127. Furthermore, resorcinol or generally a hydroxyphenol with an alcohol HO-CH ₂ -R in the presence of an aluminum catalyst at high temperatures of 200 to 400 ⁰ C can be prepared analogously to GB 1581428.

The complete disclosure of all applications, patents and publications cited above and below is incorporated by reference into this application.

A compound of the formula I can be converted with an acid into the associated acid addition salt, for example by reaction of equivalent amounts of the base and the acid in an inert

Solvents such as ethanol and subsequent evaporation. Particularly suitable acids for this reaction are those which yield physiologically acceptable salts. Thus, inorganic acids can be used, for example sulfuric acid, sulfurous acid, dithionic acid, nitric acid, hydrohalic acids such as hydrochloric acid or hydrobromic acid, phosphoric acids such as orthophosphoric acid, sulfamic acid, furthermore organic acids, in particular aliphatic, alicyclic, araliphatic, aromatic or heterocyclic mono- or polybasic carboxylic acids. , Sulfonic or sulfuric acids, eg formic acid, acetic acid, propionic acid, hexanoic acid, octanoic acid, decanoic acid, hexadecanoic acid, octadecanoic acid, pivalic acid, diethylacetic acid, malonic acid, succinic acid, pimelic acid, fumaric acid, maleic acid, Lactic acid, tartaric acid, malic acid, citric acid, gluconic acid, ascorbic acid, nicotinic acid, isonicotinic acid, methane- or ethanesulfonic acid, benzenesulfonic acid, trimethoxybenzoic acid, adamantanecarboxylic acid, p-toluenesulfonic acid, glycolic acid, embonic acid, chlorophenoxyacetic acid, aspartic acid, glutamic acid, proline,

Glyoxylic acid, palmitic acid, parachlorophenoxyisobutyric acid, cyclohexanecarboxylic acid, glucose-1-phosphate, naphthalene mono- and disulfonic acids or laurylsulfuric acid. Salts with physiologically unacceptable acids, e.g. Picrates, can be used for isolation and / or purification of the compounds of formula I.

On the other hand, compounds of formula I can be converted with bases (e.g., sodium or potassium hydroxide or carbonate) into the corresponding metal, especially alkali metal or alkaline earth metal, or into the corresponding ammonium salts.

Advantages of the compounds of the formula I or Ia as skin-lightening active ingredients or of compounds which are preferably specified may be in particular:

they are easily incorporated into preparations, they have an increased stability in preparations,

- they show no skin irritation,

- They show a high and long-lasting activity regarding their effect as skin-lightening agents.

In particular, the described compounds of the formula I or Ia are tyrosinase inhibitors, as demonstrated in the example section, and show the desired activity as skin brightener due to this property.

Another object of the present invention is a preparation or composition containing at least one compound of the formulas I or Ia, as described above, and at least one carrier suitable for topical applications. Suitable for topical purposes, means suitable for a local, in particular superficially applicable form.

The preparations are usually either topically applicable preparations, for example cosmetic, pharmaceutical or dermatological formulations, or foods or food supplements. The preparations in this case contain a cosmetically, pharmaceutically or dermatologically suitable carrier and, depending on the desired property profile, optionally further suitable ingredients. The topical preparations are preferably used as a cosmetic or dermatological preparation, particularly preferably as a cosmetic preparation. In the case of food supplements, a food of suitable carriers is used.

For the purposes of the present invention, in addition to the term preparation, the term agent, composition or formulation is used synonymously.

The compounds of the formulas I or Ia as described above are used according to the invention typically in amounts of from 0.01 to 20% by weight, preferably in amounts of from 0.05% by weight to 10% by weight, in the preparation. The expert does not have any difficulties in selecting the quantities according to the intended effect of the preparation.

Furthermore, it is recommended that the preparations according to the invention, in particular for use as a skin lightening preparation or as a cosmetic and / or pharmaceutical preparation for the prophylaxis and / or treatment of pigmentary disorders such as hyperpigmentation, freckles, age spots, sunspots and environmental Skin aging, one or more antioxidants and / or one or more vitamins.

Through the use of antioxidants, a protective effect against oxidative stress or against the action of radicals can generally be achieved, whereby the skilled person has no difficulty in selecting suitable fast or delayed-acting antioxidants.

There are many known and proven substances in the literature that can be used as antioxidants, e.g. Amino acids (eg glycine, histidine, tyrosine, tryptophan) and their derivatives, imidazoles, (eg urocanic acid) and derivatives thereof, peptides such as D, L-carnosine, D-carnosine, L-carnosine and their derivatives (eg anserine), carotenoids, Carotenes (eg α-carotene, β-carotene, lycopene) and their derivatives, chlorogenic acid and its derivatives, lipoic acid and derivatives thereof (eg dihydrolipoic acid), aurothioglucose, propylthiouracil and other thiols (eg thioredoxin, glutathione, cysteine, cystine, cystamine and their derivatives) Glycosyl, N-acetyl, methyl, ethyl, propyl, amyl, butyl and lauryl, palmitoyl, oleyl, γ-linoleyl, cholesteryl and glyceryl esters) and their salts, dilauryl thiodipropionate, distearyl thiodipropionate, thiodipropionic acid and their derivatives (esters, ethers, peptides, lipids, nucleotides, nucleosides and salts) as well as sulfoximine compounds (eg buthionine sulfoximines, homocysteinesulfoximine, buthionine sulfones, penta, hexa, heptathionine sulfoximine) in a very low tolerated dose ments (e.g. pmol to μmol / kg), furthermore (metal) chelators (eg α-hydroxyfatty acids, palmitic acid, phytic acid, lactoferrin), α-hydroxy acids (eg citric acid, lactic acid, malic acid), humic acid, bile acid, bile extracts, bilirubin, biliverdin , EDTA, EGTA and their derivatives, unsaturated fatty acids and their derivatives, vitamin C and derivatives (eg ascorbyl palmitate,

Magnesium ascorbyl phosphate, ascorbyl acetate), tocopherols and derivatives

(eg vitamin E acetate) and coniferyl benzoate of benzoin, rutin acid and its derivatives, α-glycosylrutin, ferulic acid, furfurylidene glucitol, carnosine, butylhydroxytoluene, butylhydroxyanisole, nordohydroguaretic acid, trihydroxybutyrophenone, quercitin, uric acid and its derivatives, mannose and its derivatives, zinc and its derivatives (eg ZnO, ZnSO ₄ ) , Selenium and its derivatives (eg selenium methionine), stilbenes and their derivatives (eg stilbene oxide, trans-stilbene oxide).

Suitable antioxidants are also described in WO 2006/111233 and WO 2006/111234.

Suitable antioxidants are also compounds of the general formulas A or B.

wherein

R ^{1 can be selected} from the group consisting of -C (O) CH ₃ , -CO ₂ R ³ , -C (O) NH ₂ and -C (O) N (R ⁴ ) ₂ , XO or NH,

R ^{2 is} linear or branched alkyl having 1 to 30 C atoms, R ^{3 is} linear or branched alkyl having 1 to 20 C atoms, R ^{4 are} each independently of one another H or linear or branched alkyl having 1 to 8 C atoms, s

R is linear or branched alkyl having 1 to 8 C atoms or linear or branched alkoxy having 1 to 8 C atoms and

R ⁶ denotes linear or branched alkyl having 1 to 8 C atoms, preferably derivatives of 2- (4-hydroxy-3,5-dimethoxybenzylidene) malonic acid and / or 2- (4-hydroxy-3,5-dimethoxybenzyl) - malonic acid, more preferably 2- (4-hydroxy-3,5-dimethoxybenzylidene) -malonic acid bis- (2-ethylhexyl) ester (for example Oxynex ^® ST Liquid) and / or 2- (4-hydroxy-3,5 dimethoxybenzy) malonic acid-bis (2-ethylhexyl) ester (example RonaCare ^® AP).

Mixtures of antioxidants are also suitable for use in the formulations of the invention. Known and purchasable

Mixtures mixtures are, for example comprising, as active ingredients, lecithin, L - (+) - ascorbyl palmitate and citric acid (for example (for example Oxynex ^® AP), natural tocopherols, L - (+) - ascorbyl palmitate, L - (+) -

Ascorbic acid and citric acid (for example Oxynex ^® K LIQUID), tocopherol extracts from natural sources, L - (+) - ascorbyl palmitate, L - (+) - ascorbic acid and citric acid (for example Oxynex ^® L LIQUID), DL-α-tocopherol , L - (+) - ascorbyl palmitate, citric acid and lecithin (for example Oxynex ^® LM) or butylhydroxytoluene (BHT), L - (+) - ascorbyl palmitate and citric acid (for example

Oxynex ^® 2004). Such antioxidants are with compounds of

Formula I or Ia in such compositions usually in

Percent weight ratios in the range of 1000: 1 to 1: 1000, preferably used in weight percent ratios of 100: 1 to 1: 100.

The preparations according to the invention may contain vitamins as further ingredients. Preference is given to vitamins and vitamin derivatives selected from vitamin A, vitamin A propionate, vitamin A palmitate, vitamin A acetate, retinol, vitamin B, thiamin chloride hydrochloride (vitamin B ₁ ), riboflavin (vitamin B ₂ ), nicotinamide , Vitamin C (ascorbic acid), Vitamin D, Ergocalciferol (Vitamin D ₂ ), Vitamin E, DL-α-Tocopherol, Tocopherol E-acetate, Tocopherol hydrogen succinate, Vitamin Ki, Esculin (Vitamin P active ingredient), Thiamine (Vitamin B ₁ ), Nicotinic acid (niacin), pyridoxine, pyridoxal, pyridoxamine, (vitamin B ₆ ), pantothenic acid, biotin, folic acid and cobalamin (vitamin Bi ₂ ) in the cosmetic preparations according to the invention, in particular preferably vitamin C and its derivatives, α-tocopherol, tocopherol E acetate, nicotinic acid, pantothenic acid and biotin. Vitamins are included Compounds of the formula I or Ia are usually employed in weight percent ratios in the range from 1000: 1 to 1: 1000, preferably in weight percent ratios of 100: 1 to 1: 100.

Among the phenols with antioxidant action are partially as

Naturally occurring polyphenols for pharmaceutical, cosmetic or nutritional applications particularly interesting. For example, the flavonoids or bioflavonoids, which are mainly known as plant dyes, frequently have an antioxidant potential. Effects of the substitution pattern of mono- and dihydoxy flavones are dealt with by K. Lemanska, H. Szymusiak, B. Tyrakowska, R. Zielinski, I. M. C. M. Rietjens; Current Topics in Biophysics 2000, 24 (2), 101-108. It is observed there that dihydroxyflavones having an OH group adjacent to the keto function or OH groups in the 3'4 'or 6,7 or 7,8 position have antioxidant properties, while other mono- and dihydroxyflavones have in part no antioxidant properties exhibit.

Quercetin (cyanidanol, cyanidolone 1522, meletin, sophoretine, ericin, 3,3 ', 4', 5,7-pentahydroxyflavone) is often cited as a particularly effective antioxidant (eg, CA Rice-Evans, NJ Miller, G. Paganga, Trends in Plant Science 1997, 2 (4), 152-159). K. Lemanska, H. Szymusiak, B. Tyrakowska, R. Zielinski, A.E. M.F. Soffers, I.M. CM. Rietjens; Free Radical Biology & Medicine 2001, 31 (7), 869-881 investigate the pH dependence of the antioxidant activity of

Hydroxyflavones. Quercetin shows the highest activity of the investigated structures over the entire pH range.

In order that the compounds of the formula I or Ia can develop their positive effect on the skin particularly well, it may be preferred

Let compounds of formula I or Ia penetrate deeper skin layers. There are several options available. On the one hand For example, the compounds of the formula I or Ia can have sufficient lipophilicity to be able to penetrate through the outer skin layer into epidermal layers. As a further possibility, appropriate means of transport, for example liposomes, can be provided in the preparation, which can transport the compounds of the formula I or

Ia allow through the outer skin layers. Finally, a systemic transport of the compounds of formula I or Ia is conceivable. The preparation is then, for example, designed to be suitable for oral administration.

It is also advantageous to present the compounds of formula I or Ia in encapsulated form, for. As encapsulated as cellulose or chitin capsules, in gelatin or wax matrices or with cyclodextrins.

Preparations preferred according to the invention also contain UV filters in addition to the at least one compound of the formulas I or Ia.

In principle, all UV filters are suitable for combination with the compounds of the formula I or Ia in the preparation according to the invention. Particularly preferred are those UV filters whose physiological harmlessness has already been demonstrated. For both UVA and UVB filters, there are many known and proven substances in the literature, e.g.

Benzylidenecamphor derivatives, such as 3- ^{(4'-methylbenzylidene)} -dl-camphor (for example Eusolex 6300), 3-benzylidenecamphor (for example Mexoryl® SD) ₁ polymers of N - {(2 and 4) - [(2-oxoborn-3- ylidene) methyl] benzyl} -acrylamide (eg Mexoryl® SW), N, N, N-trimethyl-4- (2-oxoborn-3-ylidenemethyl) anilinium methylsulfate (eg Mexoryl® SK) or (2-oxoborn-3-yl) yliden) toluene-4-sulfonic acid (eg Mexoryl® SL), Benzoyl or dibenzoylmethanes such as 1- (4-tert-butylphenyl) -3- (4-methoxyphenyl) propane-1,3-dione (eg Eusolex® 9020) or A-isopropyldibenzoylmethane (eg Eusolex® 8020),

Benzophenones such as 2-hydroxy-4-methoxybenzophenone (e.g., Eusolex®

4360) or 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid and its sodium salt (e.g., Uvinul® MS-40),

Methoxycinnamic acid esters such as octyl methoxycinnamate (e.g., Eusolex® 2292), isopentyl 4-methoxycinnamate, e.g. as a mixture of isomers (e.g., Neo Heliopan® E 1000),

Salicylate derivatives such as 2-ethylhexyl salicylate (e.g., Eusolex® OS), A-isopropylbenzyl salicylate (e.g., Megasol® or 3,3,5-trimethylcyclohexyl salicylate (e.g., Eusolex® HMS),

4-aminobenzoic acid and derivatives such as 4-aminobenzoic acid, 2-ethylhexyl A- (dimethylamino) benzoate (e.g., Eusolex® 6007), ethoxylated 4-aminobenzoic acid ethyl ester (e.g., Uvinul® P25),

Phenylbenzimidazole sulfonic acids, such as 2-phenylbenzimidazole-5-sulfonic acid and its potassium, sodium and triethanolamine salts (eg Eusolex® 232), 2,2- (1,4-phenylene) bisbenzimidazole-4,6-disulfonic acid or salts thereof ( eg Neoheliopan® AP) or 2,2- (1,4-phenylene) bisbenzimidazole-6-sulfonic acid;

and other substances like

2-ethylhexyl 2-cyano-3,3-diphenylacrylate (eg Eusolex® OCR), 3,3 ^' - (1,4-phenylenedimethylene) bis- (7,7-dimethyl-2-oxobicyclo- [2.2 .1] hept-1-ylmethanesulfonic acid and its salts (eg Mexoryl ^® SX) and

- 2,4,6-trianilino- (p-carbo-2 ^{^{'-ethylhexyl-1'}} -oxi) -1, 3,5-triazine (for example Uvinul ^® T 150) - 2- (4-diethylamino-2-hydroxy-benzoyl) -benzoic acid hexyl ester (Uvinul ^® example UVA Plus, BASF.).

The compounds listed in the list are examples only. Of course, other UV filters can be used.

These organic UV filters are usually incorporated in an amount of 0.5 to 10 weight percent, preferably 1-8 wt .-%, in cosmetic formulations.

Other suitable organic UV filters are e.g.

2- (2H-Benzotriazol-2-yl) -4-methyl-6- (2-methyl-3- (1,3,3,3-tetramethyl-1- (trimethylsilyloxy) disiloxanyl) propyl) phenol (INCI: Drometrizole

Trisiloxane, for example Mexoryl ^® XL)

α- (trimethylsilyl) -ω- [trimethylsilyl) oxy] poly [oxy (dimethyl) and about 6% methyl [2- [p- [2,2-bis (ethoxycarbonyl) vinyl] phenoxy] -1-methylenethyl] and about 1.5% methyl [3- [p- [2,2-bis (ethoxycarbonyl) vinyl] phenoxy) propenyl) and 0.1 to 0.4% (methylhydrogen] silylene]] (n »60) (CAS No. 207 574-

74-1) (INCI: Polysilicone-15, for example, Parsol ^® SLX) ₁

- 2,2 ^{'methylene-bis-} (6- (2H-benzotriazol-2-yl) -4- (1, 1, 3,3-tetramethyl- butyl) phenol) (CAS No. 103 597-45-. 1) (INCI: Methylene bis- benzotriazolyl Tetramethylbutylphenol, including Tinosorb M ^®). 2,2 '- (1,4-phenylene) bis (1H-benzimidazole-4,6-disulfonic acid, monosodium salt) (CAS No. 180 898-37-7),

2,4-bis - {[4- (2-ethyl-hexyloxy) -2-hydroxyl] -phenyl} -6- (4-methoxyphenyl) -

1, 3,5-triazine (CAS No. 103 597-45, 187 393-00-6) (INCI: Bis-

Ethylhexyloxyphenol Methoxyphenyl triazines, e.g. B. Tinosorb ^® S), or 4,4 ^' - [(6- [4- ((1,1-dimethylethyl) aminocarbonyl) phenylamino] -1,3,5-triazine-2,4-diyl) diimino] bis (benzoic acid 2-ethylhexyl ester) (INCI: diethylhexylbutamidotriazone Triazone such Uvasorb® ^® HEB).

Organic UV filters are usually in an amount of 0.5 to 20

Weight percent, preferably 1 to 15 wt .-%, incorporated into cosmetic formulations.

As inorganic UV filters are those from the group of titanium dioxides such as coated titanium dioxide (eg Eusolex®T-2000, Eusolex ^® T-AQUA, Eusolex ^® T-AVO), zinc oxides (eg Sachtotec®), iron oxides or cerium oxides conceivable. These inorganic UV filters are usually incorporated in an amount of 0.5 to 20 percent by weight, preferably 2 to 10 wt .-%, in cosmetic preparations.

By combining one or more compounds of formula I or Ia with other UV filters, the protective effect against harmful effects of UV radiation can be optimized. This results in broadband protection systems that can be supplemented by the addition of inorganic UV filters.

All mentioned UV filters can also be used in encapsulated form. In particular, it is advantageous to use organic UV filters in encapsulated form. In detail, there are the following advantages:

- The hydrophilicity of the capsule wall can be adjusted independently of the solubility of the UV filter. For example, hydrophobic UV filters can also be incorporated into purely aqueous preparations. In addition, the often perceived as unpleasant oily impression when applying the hydrophobic UV filter containing preparation is suppressed. Certain UV filters, in particular dibenzoylmethane derivatives, show only reduced photostability in cosmetic preparations. By encapsulating these filters or compounds that affect the photostability of these filters, such as cinnamic acid derivatives, the photostability of the entire formulation can be increased.

In the literature, the skin penetration through organic UV filters and the associated irritation potential during direct application to the human skin is discussed again and again. The encapsulation of the corresponding substances proposed here prevents this effect.

- Generally, by encapsulation of individual UV filters or other ingredients preparation problems caused by interaction of individual preparation components with each other, such as crystallization processes, precipitation and agglomeration can be avoided because the interaction is prevented.

Therefore, it is preferred if one or more of the above-mentioned UV filters are present in encapsulated form. It is advantageous if the capsules are so small that they can not be observed with the naked eye. To achieve the o.g. Effects it is still necessary that the capsules are sufficiently stable and donate the encapsulated active ingredient (UV filter) not or only to a small extent to the environment.

Suitable capsules may have walls of inorganic or organic polymers. For example, in US 6,242,099 B1 the

Preparation of suitable capsules with walls of chitin, chitin derivatives or polyhydroxylated polyamines described. Capsules which are particularly preferred for use in accordance with the invention have walls which can be obtained by a SolGel process, as described in applications WO 00/09652, WO 00/72806 and WO 00/71084.

Again, capsules whose walls are made up of silica gel (silica, undefined silicon oxide hydroxide) are preferred. The production corresponding capsules is known to those skilled in the art, for example, from the cited patent applications, whose content is expressly also part of the present application.

The capsules in preparations according to the invention are preferably present in amounts which ensure that the encapsulated UV filters are present in the preparation in the amounts indicated above.

The preparations according to the invention may also contain one or more further skin-lightening active ingredients. In principle, skin-lightening active ingredients can be all active ingredients known to the person skilled in the art. Examples of compounds with skin-lightening activity are hydroquinone, kojic acid, arbutin, aloesin or rucinol.

The preparations according to the invention can moreover be further

Anti-aging agents, anti-cellulite agents or conventional skin-friendly or skin-care agents included. Skin-sparing or skin-care active ingredients can, in principle, be all active ingredients known to the person skilled in the art.

Particularly preferred anti-aging agents are pyrimidinecarboxylic acids, aryloximes, bioflavonoids, bioflavonoid-containing extracts, chromones or retinoids.

Pyrimidinecarboxylic acids occur in halophilic microorganisms and play a role in the osmoregulation of these organisms (EA Galinski et al., Eur. J. Biochem., 149 (1985) page 135-139). In particular, ectoine ((S) -1, 4,5,6-tetrahydro-2-methyl-4-pyrimidinecarboxylic acid) and hydroxyectoine ((S ₁ S) -1,5,6-tetrahydro-5 are among the pyrimidinecarboxylic acids These compounds stabilize enzymes and other biomolecules in aqueous solutions and organic solvents. In particular, they stabilize enzymes against denaturing conditions such as salts, extreme pH, surfactants, urea, guanidinium chloride and other compounds.

Ectoine and ectoine derivatives such as hydroxyectoine can be used to advantage in medicines. In particular, hydroxyectoine can be used for the manufacture of a medicament for the treatment of skin diseases. Other uses of hydroxyectoine and other ectoine derivatives are typically in areas where e.g. Trehalose is used as an additive. So may ectoin derivatives, such as

Hydroxyectoin, as a protective substance in dried yeast and bacterial cells use. Also pharmaceutical products such as non-glycosylated, pharmaceutically active peptides and proteins e.g. t-PA can be protected with Ectoin or its derivatives.

Among the cosmetic applications, the use of ectoine and ectoine derivatives for the care of aged, dry or irritated skin should be mentioned in particular. For example, European Patent Application EP-A-0 671 161 describes that ectoine and hydroxyectoine are used in cosmetic preparations, such as powders, soaps, surfactant-containing

Cleaning products, lipsticks, blushes, make-ups, skin care creams and sunscreen preparations.

In this case, a pyrimidinecarboxylic acid according to the formula below is preferably used,

wherein R ¹ is a radical H or Ci _-8 alkyl, R ² is a radical H or C _1-4 alkyl and R ^3, R ^4, R ⁵ and R ⁶ each independently represent a radical from the group H, OH ₁ NH ₂ and Ci. ₄ alkyl. Preference is given to using pyrimidinecarboxylic acids in which R ^{2 is} a methyl or an ethyl group and R ¹ or R ⁵ and R ^{6 are} H. Particularly preferred are the pyrimidinecarboxylic acids ectoine ((S) -1, 4,5,6-tetrahydro-2-methyl-4-pyrimidinecarboxylic acid) and hydroxyectoine ((S, S) -1, 4,5,6- Tetrahydro-5-hydroxy-2-methyl-4-pyrimidine-carboxylic acid) used. The preparations according to the invention contain such pyrimidinecarboxylic acids, preferably in amounts of up to 15% by weight. The pyrimidinecarboxylic acids are preferably used in ratios by weight of 100: 1 to 1: 100 to the compounds of the formula I, weight percent ratios in the range from 1:10 to 10: 1 being particularly preferred.

Among the aryl oximes, 2-hydroxy-5-methyllaurophenone oxime, which is also referred to as HMLO, LPO or F5, is preferably used. Its suitability for use in cosmetic products is known for example from the German patent application DE-A-41 16 123. Preparations containing 2-hydroxy-5-methyllaurophenone oxime are accordingly suitable for the treatment of skin diseases which are associated with inflammation. The preparations preferably contain from 0.01 to 10% by weight of the aryloxime, and it is particularly preferred if the preparation contains from 0.05 to 5% by weight of aryloxime.

Known bioflavonoids are, for example, troxerutin, tiliroside, α-glucosylrutin, rutin or isoquercetin, the said selection not being intended to be restrictive.

Bioflavonoidhaltige extracts are for example Gingko Biloba or Emblica.

Known anti-aging substances are also chromones, as described, for example, in EP 1508327 or retinoids, for example retinol (vitamin A), Retinoic acid, retinaldehyde or synthetically modified compounds of vitamin A.

The described chromones and retinoids are also effective anti-cellulite agents. A well-known anti-cellulite

Active ingredient is caffeine.

The compositions may comprise or contain, consist essentially of or consist of the necessary or optional ingredients or ingredients mentioned. All connections or

Components that can be used in the formulations are either known and commercially available or can be synthesized by known methods.

The one or more compounds of the formula I or Ia, as described above, can be incorporated in the usual way into cosmetic or dermatological preparations. Suitable preparations for external use, for example as a cream, lotion, gel, or as a solution that can be sprayed on the skin. For internal use, administration formulas such as capsules, dragees, powders, tablet solutions or solutions are suitable.

As an application form of the preparations according to the invention are, for example: solutions, suspensions, emulsions, PIT emulsions, pastes, ointments, gels, creams, lotions, powders, soaps, surfactant-containing cleaning preparations, oils, aerosols and sprays. Other forms of application include sticks, shampoos and shower baths. Any customary carrier substances, adjuvants and optionally further active ingredients can be added to the preparation. Preferable excipients come from the group of preservatives, stabilizers, solubilizers, colorants, ie pigments or dyes or odor improvers.

Ointments, pastes, creams and gels may contain the usual excipients, e.g. animal and vegetable fats, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc and zinc oxide or mixtures of these substances.

Powders and sprays may contain the usual carriers, e.g.

Lactose, talc, silicic acid, aluminum hydroxide, calcium silicate and polyamide powder or mixtures of these substances. Sprays may additionally contain the usual propellants, e.g. Chlorofluorocarbons, propane / butane or dimethyl ether.

Solutions and emulsions may contain the usual excipients such as solvents, solubilizers and emulsifiers, e.g. Water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylglycol, oils, in particular cottonseed oil, peanut oil, corn oil, olive oil, castor oil and sesame oil, glycerin fatty acid esters, polyethylene glycols and fatty acid esters of sorbitan or mixtures contain these substances.

Suspensions may be the usual carriers such as liquid diluents, e.g. Water, ethanol or propylene glycol, suspending agents, e.g. ethoxylated isostearyl alcohols, polyoxyethylene sorbitol esters and polyoxyethylene sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth or mixtures of these substances.

Soaps may contain the usual excipients such as alkali salts of fatty acids, salts of fatty acid monoesters, fatty acid protein hydrolysates, isothionates, Lanolin, fatty alcohol, vegetable oils, plant extracts, glycerol, sugar or mixtures of these substances.

Surfactant-containing cleaning products may include the usual excipients such as salts of fatty alcohol sulfates, fatty alcohol ether sulfates, sulfosuccinic monoesters, fatty acid protein hydrolysates, isothionates, imidazolinium derivatives, methyl taurates, sarcosinates, fatty acid amide ether sulfates, alkyl amidobetaines, fatty alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable and synthetic oils, lanolin derivatives, ethoxylated glycerol - Contain fatty acid esters or mixtures of these substances.

Facial and body oils may contain the usual excipients such as synthetic oils such as fatty acid esters, fatty alcohols, silicone oils, natural oils such as vegetable oils and oily vegetable extracts, paraffin oils, lanolin oils or mixtures of these substances.

Other typical cosmetic application forms are also powder, emulsion and wax make-up as well as sunscreen, pre-sun and after-sun preparations.

The preferred preparation forms according to the invention include in particular emulsions.

Emulsions of the invention are advantageous and contain z. As mentioned fats, oils, waxes and other fatty substances, and water and an emulsifier, as it is commonly used for such a type of preparation.

The lipid phase can advantageously be chosen from the following substance group:

- mineral oils, mineral waxes - Oils such as triglycerides of capric or caprylic, further natural oils such. Castor oil;

Fats, waxes and other natural and synthetic fats, preferably esters of fatty acids with lower C-number alcohols, e.g. with isopropanol, propylene glycol or glycerol, or esters of fatty acids

Alcohols with low C-alkanoic acids or with fatty acids;

- Silicone oils such as dimethylpolysiloxanes, diethylpolysiloxanes, diphenylpolysiloxanes and mixed forms thereof.

The oil phase of the emulsions, oleogels or hydrodispersions or lipodispersions in the context of the present invention is advantageously selected from the group of esters of saturated and / or unsaturated, branched and / or unbranched alkanecarboxylic acids having a chain length of 3 to 30 carbon atoms and saturated and / or or unsaturated, branched and / or unbranched alcohols having a chain length of 3 to 30 carbon atoms, from the group of esters of aromatic carboxylic acid and saturated and / or unsaturated, branched and / or unbranched alcohols having a chain length of 3 to 30 carbon atoms. Such ester oils can then advantageously be selected from the group isopropyl myristate, isopropyl palmitate, isopropyl stearate, isopropyl oleate, n-butyl stearate, n-hexyl laurate, n-decyl oleate, isooctyl stearate, isononyl stearate, isononyl isononanoate, 2-ethylhexyl palmitate, 2-ethylhexyl laurate, 2-hexadecyl stearate, 2 Octyldodecyl palmitate, oleyl oleate, oleyl erucate, acyl oleate, erucyl erucate and synthetic, semi-synthetic and natural mixtures of such esters, eg. B. jojoba oil.

Furthermore, the oil phase can advantageously be selected from the group of branched and unbranched hydrocarbons and waxes, silicone oils, dialkyl ethers, the group of saturated or unsaturated, branched or unbranched alcohols, and fatty acid triglycerides, in particular the triglycerol esters of saturated and / or unsaturated, branched and / or unbranched alkanecarboxylic acids of one chain length from 8 to 24, in particular 12-18 C atoms. The fatty acid triglycerides can be selected, for example, advantageously from the group of synthetic, semi-synthetic and natural oils, for. For example, olive oil, sunflower oil, soybean oil, peanut oil, rapeseed oil, almond oil, palm oil, coconut oil, palm kernel oil and the like.

Any mixtures of such oil and wax components are also advantageous to use in the context of the present invention. It may also be advantageous, if appropriate, to use waxes, for example cetyl palmitate, as the sole lipid component of the oil phase.

The oil phase is selected from the group 2-ethylhexyl isostearate, octyldodecanol, isotridecyl isononanoate, isoeicosane, 2-ethylhexyl cocoate advantageous C-i2-i ₅ alkyl benzoate, caprylic capric triglyceride, dicapryl ether.

Particularly advantageous are mixtures of C-ι -i ₂ ₅ alkyl benzoate and 2-ethylhexyl isostearate, mixtures of C ₂ -i ₅ alkyl benzoate and isotridecyl isononanoate and mixtures of C ₂ -i ₅ alkyl benzoate, 2-ethylhexyl isostearate and isotridecyl isononanoate.

Of the hydrocarbons, paraffin oil, squalane and squalene are to be used advantageously in the context of the present invention.

Advantageously, the oil phase can also have a content of cyclic or linear silicone oils or consist entirely of such oils, although it is preferred to use an additional content of other oil phase components in addition to the silicone oil or silicone oils.

Advantageously, cyclomethicone (octamethylcyclotetrasiloxane) is used as the silicone oil to be used according to the invention. However, other silicone oils are also advantageous in the context of the present invention use, for example hexamethylcyclotrisiloxane, polydimethylsiloxane, poly (methylphenylsiloxane).

Also particularly advantageous are mixtures of cyclomethicone and Iso tridecylisononanoat, from cyclomethicone and 2-Ethylhexylisostearat.

If appropriate, the aqueous phase of the preparations according to the invention advantageously contains alcohols, diols or polyols of low C number, and also their ethers, preferably ethanol, isopropanol, propylene glycol, glycerol, ethylene glycol, ethylene glycol monoethyl or monobutyl ether,

Propylene glycol monomethyl, monoethyl or monobutyl ether, diethylene glycol monomethyl or monoethyl ether and analogous products, furthermore lower C number alcohols, e.g. As ethanol, isopropanol, 1, 2-propanediol, glycerol, and in particular one or more thickeners, which or which can be advantageously selected from the group

Silica, aluminum silicates, polysaccharides or their derivatives, e.g. Hyaluronic acid, xanthan gum, hydroxypropylmethylcellulose, particularly advantageous from the group of polyacrylates, preferably a polyacrylate from the group of so-called Carbopols, for example Carbopols types 980, 981, 1382, 2984, 5984, each individually or in combination.

In particular, mixtures of the abovementioned solvents are used. For alcoholic solvents, water can be another ingredient.

Emulsions of the invention are advantageous and contain z. As mentioned fats, oils, waxes and other fatty substances, and water and an emulsifier, as it is usually used for such a type of Formu- tion.

In a preferred embodiment, the preparations according to the invention contain hydrophilic surfactants. The hydrophilic surfactants are preferably selected from the group of alkylglucosides, acyl lactylates, betaines and cocoamphoacetates.

The alkylglucosides in turn are advantageously selected from the group of alkylglucosides, which are represented by the structural formula

in which R is a branched or unbranched alkyl radical

4 to 24 carbon atoms and wherein DP means a mean degree of glucosylation of up to 2.

The value DP represents the degree of glucosidation of the alkylglucosides used in the invention and is defined as

DP = 7 + 2 + 3 + ... = Σ i

100 100 100 100

In this case, pi, P2, P ₃ ... Or p 1 represent the proportion of products which are mono-, di-trisubstituted ... times glucosylated in weight percentages. According to the invention, products having degrees of glucosylation of 1-2, in particular advantageously of 1 , 1 to 1, 5, very particularly advantageously selected from 1, 2-1, 4, in particular from 1, 3. The value DP takes into account the fact that alkylglucosides, as a rule, are mixtures of mono- and oligoglucosides. Advantageously in accordance with the invention is a relatively high content of monoglucosides, typically of the order of 40-70% by weight.

Alkylglylcosides used particularly advantageously according to the invention are selected from the group octylglucopyranoside, nonylglucopyranoside, decylglucopyranoside, undecylglucopyranoside, dodecylglucopyranoside, tetradecylglucopyranoside and hexadecylglucopyranoside.

It is also advantageous, natural or synthetic raw materials and auxiliary materials or to use mixtures which are distinguished by an effective content of the active ingredients used according to the invention, for example Plantaren ^® 1200 (Henkel KGaA), Oramix NS ^® 10 (Seppic).

In turn, the acyl lactylates are advantageously selected from the group of substances which are defined by the structural formula

M®, wherein R ^{1 is} a branched or unbranched alkyl radical having 1 to 30 carbon atoms and M ^{+ is selected} from the group of alkali ions and the group of substituted with one or more alkyl and / or with one or more hydroxyalkyl radicals ammonium ions or half the equivalent of an alkaline earth metal equivalent.

Sodium is advantageous, for example isostearyllactylat, for example the product Pathionic ^® ISL from the American Ingredients Company. The betaines are advantageously selected from the group of substances which are defined by the structural formula

R ² -C-NH4CH ₂ 4-N-CH ₂ -C ^κ

CH ₃ _n , where R ^{2 is} a branched or unbranched alkyl radical having 1 to 30 carbon atoms.

Particularly advantageously, R ^{2 is} a branched or unbranched alkyl radical having 6 to 12 carbon atoms. 5

Capramidopropylbetaine, for example, is advantageous

Product Tego ^® betaine 810 from the company Th. Goldschmidt AG.

As inventively advantageous cocoamphoacetate example, sodium _Q is selected as under the name Miranol ^® Ultra C32 from Miranol Chemical Corp. is available.

The preparations according to the invention are advantageously characterized in that the hydrophilic or surfactant (s) in concentrations of ₅ 0.01-20 wt .-%, preferably 0.05-10 wt .-%, particularly preferably 0.1-5 wt .-%, in each case based on the total weight of the composition, is present or present.

For use, the cosmetic and dermatological preparations according to the invention are applied in sufficient quantity to the skin in the manner customary for cosmetics. Cosmetic and dermatological preparations according to the invention can be present in various forms. So they can z. For example, a solution, an anhydrous preparation, an emulsion or microemulsion of the water-in-oil (W / O) type or of the oil-in-water (O / W) type, a multiple emulsion, for example of the Waser-in type. oil-in-water

(W / O / W), a gel, a solid stick, an ointment or even an aerosol. It is also advantageous to present Ectoine in encapsulated form, e.g. In collagen matrices and other common encapsulating materials, e.g. As encapsulated cellulose, in gelatin, wax matrices or liposomally encapsulated. In particular wax matrices as described in DE-OS 43 08 282, have been found to be favorable. Preference is given to emulsions. O / W emulsins are especially preferred. Emulsions, W / O emulsions and O / W emulsions are available in the usual way.

As emulsifiers, for example, the known W / O and O / W emulsifiers can be used. It is advantageous to use further customary co-emulsifiers in the preferred O / W emulsions according to the invention.

According to the invention, suitable co-emulsifiers are, for example, O / W emulsifiers, primarily from the group of substances with HLB values of 11-16, very particularly advantageously with HLB values of 14.5-15.5, provided that the O / W emulsifiers have W emulsifiers have saturated radicals R and R ¹ . If the O / W emulsifiers have unsaturated radicals R and / or R ', or if isoalkyl derivatives are present, the preferred HLB value of such emulsifiers may also be lower or higher.

It is advantageous to choose the fatty alcohol ethoxylates from the group of ethoxylated stearyl alcohols, cetyl alcohols, cetylstearyl alcohols (cetearyl alcohols). Particularly preferred are: polyethylene glycol (13) stearyl ether (steareth-13), polyethylene glycol (14) stearyl ether (steareth-14), polyethylene glycol (15) stearyl ether (steareth-15), polyethylene glycol (16) stearyl ether (steareth-16), polyethylene glycol (17) stearyl ether (steareth-17), polyethylene glycol (18) stearyl ether (steareth-18), polyethylene glycol (19) stearyl ether (Steareth-19), polyethylene glycol (20) stearyl ether (steareth-20), polyethylene glycol (12) isostearyl ether (isosteareth-12), polyethylene glycol (13) isostearyl ether (isosteareth-13), polyethylene glycol (14) - isostearyl ether (isosteareth- 14), polyethylene glycol (15) isostearyl ether (isosteareth-15), polyethylene glycol (16) isostearyl ether (isosteareth-16), polyethylene glycol (17) isostearyl ether (isosteareth-17), polyethylene glycol (18) isostearyl ether (isosteareth-18), polyethylene glycol (19) isostearyl ether (isosteareth-19), polyethylene glycol (20) - isostearyl ether (isosteareth-20), polyethylene glycol (13) cetyl ether (ceteth-13), polyethylene glycol (14) cetyl ether (ceteth-14), polyethylene glycol (15) cetyl ether (Ceteth-15), polyethylene glycol (16) cetyl ether (ceteth-16), polyethylene glycol (17) cetyleth he (ceteth-17), polyethylene glycol (18) cetyl ether (ceteth-18), polyethylene glycol (19) cetyl ether (ceteth-19), polyethylene glycol (20) cetyl ether (ceteth-20), polyethylene glycol (13) isocetyl ether (Isoceteth-13), Polyethylene glycol (14) Isocetyl ether (Isoceteth-14), Polyethylene glycol (15) Isocetyl ether (Isoceteth-15), Polyethylene glycol (16) Isocetyl ether (Isoceteth-16), Polyethylene glycol (17) - Isocetyl ether (Isoceteth-17) , Polyethylene glycol (18) isocetyl ether (isoceteth-18), polyethylene glycol (19) isocetyl ether (isoceteth-19), polyethylene glycol (20) isocetyl ether (isoceteth-20), polyethylene glycol (12) oleyl ether (oleth-12), polyethylene glycol (13 oleyl ether (Oleth-13), polyethylene glycol (14) oleyl ether (Oleth-14), polyethylene glycol (15) oleyl ether (Oleth-15), polyethylene glycol (12) lauryl ether (laureth-12), polyethylene glycol (12) - isolauryl ether ( isololeth-12), polyethylene glycol (13) cetyl stearyl ether (ceteareth-13), polyethylene glycol (14) cetyl stearyl ether (ceteareth-14), polyethylene glycol (15) cetyl stearyl ether (C eteareth-15), polyethylene glycol (16) cetyl stearyl ether (ceteareth-16), polyethylene glycol (17) cetyl stearyl ether (ceteareth-17), polyethylene glycol (18) cetyl stearyl ether (Ceteareth-18), polyethylene glycol (19) cetyl stearyl ether (Ceteareth-19), polyethylene glycol (20) cetyl stearyl ether (Ceteareth-20).

It is also advantageous to choose the fatty acid ethoxylates of the following group:

Polyethylene glycol (20) stearate, polyethylene glycol (21) stearate, polyethylene glycol (22) stearate, polyethylene glycol (23) stearate, polyethylene glycol (24) stearate, polyethylene glycol (25) stearate, polyethylene glycol (12) isostearate, polyethylene glycol (13) isostearate, polyethylene glycol ( 14) isostearate, polyethylene glycol (15) isostearate, polyethylene glycol (16) isostearate, polyethylene glycol (17) isostearate, polyethylene glycol (18) isostearate, polyethylene glycol (19) isostearate, polyethylene glycol (20) isostearate, polyethylene glycol (21) isostearate, polyethylene glycol (22) isostearate, polyethylene glycol (23) isostearate, polyethylene glycol (24) isostearate, polyethylene glycol (25) isostearate, polyethylene glycol (12) oleate, polyethylene glycol (13) oleate, polyethylene glycol (14) oleate, polyethylene glycol (15) oleate, polyethylene glycol (16) oleate, Polyethylene glycol (17) oleate, polyethylene glycol (18) oleate, polyethylene glycol (19) oleate, polyethylene glycol (20) oleate,

As the ethoxylated alkyl ether carboxylic acid or its salt, the sodium laureth-11-carboxylate can be advantageously used. As the alkyl ether sulfate, sodium laureth-4 sulfate can be advantageously used. As the ethoxylated cholesterol derivative, polyethylene glycol (30) cholesteryl ether can be advantageously used. Also polyethylene glycol (25) soybean oil has been proven. As ethoxylated triglycerides, the polyethylene glycol (60) Evening Primrose Glycerides can advantageously be used (Evening Primrose = evening primrose). It is furthermore advantageous to use the polyethylene glycol glycerol fatty acid esters from the group consisting of polyethylene glycol (20) glyceryl laurate, polyethylene glycol (21) glyceryl laurate, polyethylene glycol (22) glyceryl laurate, polyethylene glycol (23) glyceryl laurate, polyethylene glycol (6) glyceryl caprate / citrate, polyethylene glycol (20 ) glyceryl oleate, polyethylene glycol (20) glyceryl isostearate, polyethylene glycol (18) glyceryl oleate (cocoate).

It is also favorable to choose the sorbitan esters from the group of polyethylene glycol (20) sorbitan monolaurate, polyethylene glycol (20) sorbitan monostearate, polyethylene glycol (20) sorbitan monoisostearate, polyethylene glycol (20) sorbitan monopalmitate, polyethylene glycol (20) sorbitan monooleate.

As optional, but according to the invention optionally advantageous VWO emulsifiers can be used:

Fatty alcohols having 8 to 30 carbon atoms, monoglycerol esters of saturated and / or unsaturated, branched and / or unbranched alkanecarboxylic acids having a chain length of 8 to 24, in particular 12-18 C atoms, diglycerol esters of saturated and / or unsaturated, branched and / or unbranched alkanecarboxylic acids a chain length of 8 to 24, in particular 12-18 C-atoms, monoglycerol ethers of saturated and / or unsaturated, branched and / or unbranched alcohols of a chain length of 8 to 24, in particular 12-18 C-atoms, diglycerol ethers saturated and / or unsaturated, branched and / or unbranched alcohols of a chain length of 8 to 24, in particular 12-18 C-atoms, propylene glycol esters of saturated and / or unsaturated, branched and / or unbranched alkanecarboxylic acids having a chain length of 8 to 24, in particular 12-18 C-atoms and sorbitan esters saturated and / or unsaturated, branched and / or unbranched alkanecarboxylic acids of a Chain length of 8 to 24, in particular 12-18 C atoms. Particularly advantageous W / O emulsifiers are glyceryl monostearate, glyceryl monoisostearate, glyceryl monomyristate, glyceryl monooleate, diglyceryl monostearate, diglyceryl monoisostearate, propylene glycol monostearate, propylene glycol monoisostearate, propylene glycol monocaprylate, propylene glycol monolaurate, sorbitan monoisostearate, sorbitan monolaurate,

Sorbitan monocaprylate, sorbitan monoisooleate, sucrose distearate, cetyl alcohol, stearyl alcohol, arachidyl alcohol, behenyl alcohol, isobehenyl alcohol, selachyl alcohol, chimyl alcohol, polyethylene glycol (2) stearyl ether (steareth-2), glyceryl monolaurate, glyceryl monocaprinate, glyceryl mono- caprylate or PEG-30 dipolyhydroxystearate.

The compositions or preparations described are particularly suitable for whitening human skin or for the prophylaxis and / or treatment of pigment disorders such as hyperpigmentation, freckles, age spots, sun spots and environmental aging of the skin. They are present in various dosage forms commonly used for this application. Thus, the preparation in particular as a lotion or emulsion, such as cream or milk (O / W, W / O, O / W / O, W / O / W), in the form of oily-alcoholic, oily-aqueous or aqueous-alcoholic Gels or solutions, be present as solid pens or formulated as an aerosol.

The preparation may contain cosmetic adjuvants which are commonly used in this type of preparation, e.g. Thickening agents, emollients, humectants, surfactants, emulsifiers, preservatives, antifoaming agents, perfumes, waxes, lanolin, propellants, dyes and / or pigments which color the agent itself or the skin, and other ingredients commonly used in cosmetics.

Dyes used are preferably approved dyes listed in the Cosmetics Regulation, Appendix 3 as a positive list. As preservatives preferably approved preservatives are used, which are listed in the Cosmetics Regulation, Appendix 6 as a positive list or antimicrobial pigments, as described for example in WO 2004/0092283 or WO 2004/091567.

Suitable preservatives are therefore also alkyl esters of p-hydroxybenzoic acid, hydantoin derivatives, propionate salts or a variety of ammonium compounds.

Very particularly preferred preservatives are methylparaben, propylparaben, imidazolidinyl urea, sodium dehydroxyacetate or benzyl alcohol. Preservatives are used in amounts between 0.5 to 2 wt .-%.

Emollients or plasticizers are often incorporated into cosmetic preparations. They are preferably used in 0.5 to 50 wt .-%, preferably between 5 and 30 wt .-% based on the total composition. In general, plasticizers can be classified into classes, such as the category of esters, fatty acids or fatty alcohols, polyols, hydrocarbons and oils containing at least one amide structure unit.

Representative oils containing at least one amide structure unit together with their synthesis are described in particular in EP 1044676 and EP 0928608. A particularly preferred compound is isopropyl N-lauroyl sarcosinate, which is commercially available under the product name Eldew SL-205 from Ajinomoto.

Among the esters, mono or diesters may be selected. Examples in this regard are dibutyl adipate, diethyl sebacate, diisopropyl dimerate or dioctyl succinate. Branched fatty acid esters are, for example, 2-ethyl hexyl myristate, isopropyl stearate or isostearyl palmitate. Tribasic esters are, for example, trisopropyl trilinoleate or trilauryl citrate. Straight-chain fatty acid esters are, for example, lauryl palmitate, myristyl lactate, oleyl eurcat or stearyl oleate. Preferred esters are coco-caprylates / caprate (= INCI name, esters of coconut oil fatty alcohols with saturated medium-chain fatty acids), propylene glycol myristyl ether acetate, diisopropyl adipate or cetyl octanoate.

Suitable fatty alcohols and acids are compounds having 10 to 20 carbon atoms. Particularly preferred compounds are cetyl, myristyl, palmitic or stearic alcohol or acid.

Suitable polyols are linear or branched-chain alkyl polyhydroxy compounds, for example propylene glycol, sorbitol or glycerol. However, it is also possible to use polymeric polyols, for example polypropylene glycol or polyethylene glycol. Butylene and propylene glycol are also particularly suitable compounds for enhancing the penetration.

Exemplary hydrocarbons as plasticizers are compounds that generally have 12 to 30 carbon atoms. Specific examples are arylalkyl benzoates, alkyl benzoates, mineral oils, petrolatum, squalene or isoparaffins.

Additional emollients or hydrophobizing agents are preferably C ₂ to C ₅ - alkyl benzoates, dioctyladipate, octyl stearate, octyldodecanol, hexyl laurate, octyldodecyl neopentanoate, cyclomethicone, Dicapryl ether, dimethicone, phenyl trimethicone, isopropyl myristate, Capriylic / capric glycerides, propylene glycol dicaprylate / dicaprate or decyl oleate.

Another category of functional ingredients of cosmetic preparations are thickening agents. Thickeners are in dr rule in amounts between 0.1 to 20 wt .-%, preferably between 0.5 to 10 wt .-% based on the total amount used. Exemplary of these compounds are crosslinked polyacrylate materials, available commercially under the Carbopol brand from BF Goodrich Company. Thickeners, such as xanthan gum, carrageenan, can also be used.

Gum, gelatin gum, karaya gum, pectin gum or locust bean gum.

In some circumstances, it is possible that a compound may be both a thickener and a plasticizer. Examples of these are silicone gums (kinematic viscosity> 10 centistokes), esters such as glycerol stearate or cellulose derivatives, for example hydroxypropyl cellulose.

It is possible to use as dispersion or solubilizing agent an oil, wax or other fatty substance, a low monoalcohol or a low polyol or mixtures thereof. Particularly preferred monoalcohols or polyols include ethanol, i-propanol, propylene glycol, glycerine and sorbitol.

A preferred embodiment of the invention is an emulsion which is present as a protective cream or milk and contains, for example, fatty alcohols, fatty acids, fatty acid esters, in particular triglycerides of fatty acids, lanolin, natural and synthetic oils or waxes and emulsifiers in the presence of water.

Further preferred embodiments are oily lotions based on natural or synthetic oils and waxes, lanolin, fatty acid esters, in particular triglycerides of fatty acids, or oily alcoholic lotions based on a lower alcohol, such as ethanol, or a glycerol, such as propylene glycol, and / or a polyol like glycerine, and oils, waxes and fatty acid esters, such as triglycerides of fatty acids.

The preparation of the invention may also be present as an alcoholic gel containing one or more lower alcohols or polyols, such as

Ethanol, propylene glycol or glycerin, and a thickening agent such as silica. The oily-alcoholic gels also contain natural or synthetic oil or wax.

The solid sticks consist of natural or synthetic waxes and oils, fatty alcohols, fatty acids, fatty acid esters, lanolin and other fatty substances.

If a preparation is formulated as an aerosol, the customary propellants, such as alkanes, fluoroalkanes and chlorofluoroalkanes, are generally used.

Further objects of the present invention are a process for the preparation of a preparation, which is characterized in that one or more compounds of the formula I or Ia with radicals as described above, with a carrier suitable for topical applications, for example a cosmetically, pharmaceutically or dermatologically suitable Carrier, is mixed.

The same applies to the preparation of a dietary supplement, characterized in that one or more compounds of the formula I or Ia with residues as described above, is mixed with a carrier suitable for food.

The preparations according to the invention can be prepared using techniques which are well known to the person skilled in the art. The mixing may result in dissolution, emulsification or dispersion of the at least one compound of formula I or Ia as described above in the carrier.

Equally positive are the properties of compounds of the formula I or Ia, as described above, for use in foods or as dietary supplements or as a "functional food." The further explanations given to foods apply mutatis mutandis to dietary supplements and "functional food ".

The foodstuffs include all materials which are suitable for consumption by animals or for human consumption, for example vitamins and provitamins thereof, fats, minerals or amino acids. "The foods may be solid or liquid, ie present as a beverage.

Further objects of the present invention are accordingly the use of at least one compound of the formula I or Ia as a food additive for human or animal nutrition and preparations which are food or dietary supplements and contain appropriate carriers.

For the purposes of the invention, foods are, for example, foodstuffs derived from a single natural source, e.g. Sugar, unsweetened juice, nectar or puree from a single plant species, e.g. unsweetened apple juice (eg also a mixture of different types of apple juice), grapefruit juice, orange juice, apple compote, apricot nectar, tomato juice, tomato sauce, tomato puree etc. Further examples of foods which can be enriched according to the present invention with one or more compounds of formula I or Ia , grain or cereal are a single plant species and

Materials made from such plant species, such as corn syrup, rye flour, wheat flour or oat bran. Also Mixtures of such foods are suitable, for example multi-vitamin preparations, mineral mixtures or sweetened juice. Other examples of foods include food preparations such as prepared cereals, biscuits, mixed drinks, foods specially formulated for children such as yoghurt, diet foods, low calorie foods or animal foods.

The foods thus include all edible combinations of carbohydrates, lipids, proteins, inorganic elements, trace elements, vitamins, water or active metabolites of plants and animals.

The foods are preferably administered orally, e.g. in the form of food, pills, tablets, capsules, powders, syrups, solutions or suspensions.

The foods of the invention can be prepared by techniques well known to those skilled in the art.

Due to their action compounds of formula I are also suitable as a drug ingredient.

In the following the invention is explained in more detail by means of examples, the invention is executable throughout the claimed range and not limited to the examples mentioned here.

Examples:

Example 1: Synthesis of 6-hexyl-7-hydroxychroman-2-one

To a light yellow suspension of 4-hexylresorcinol (257 mmol) in toluene (250 ml) is added acrylic acid (328 mmol). Subsequently, 3.5 g of Amberlyst-15 are added and the yellow reaction solution is heated for about 21 h under reflux at the water. The orange reaction solution is mixed with activated charcoal and heated for about 1 h at reflux. Amberlyst-15 and activated carbon are filtered off and the solvent is distilled off. 6-hexyl-7-hydroxychroman-2-one is obtained.

1 H NMR (DMSO-d6) δ 9.48 (s, 1H), 6.95 (s, 1H), 6.49 (s, 1H), 2.85 (dd, J = 7.6, 6.7 Hz, 2H), 2.74 (dd , J = 7.6, 5.5 Hz, 2H), 2.49 (t, J = 7.7 Hz, 2H), 1.57- 1.46 8m, 2H), 1.35-1.24 (m, 6H), 0.09 (t, J = 6.7 Hz , 3H). EI-MS: 248.1 (M +), 177.0, 149.0, 69.0

Example 2: Synthesis of 6-ethyl-7-hydroxychroman-2-one

Analogously to Example 1, 4-ethylresorcinol and acrylic acid are reacted.

1 H NMR (DMSO-d6) δ 9.51 (s, 1H), 6.97 (s, 1H), 6.49 (s, 1H), 2.86 (dd, J =

7.7, 6.6 Hz, 2H), 2.74 (m, 2H), 2.51 (q, J = 7.4 Hz, 2H), 1.13 (t, J = 7.4 Hz,

3H).

EI-MS: 192.1 (M +), 177.0, 149.0, 122.1, 107.0, 69.0.

Example 3: Synthesis of 7-hydroxychroman-2-one

Resorcinol and acrylic acid are reacted analogously to Example 1. 1 H NMR (DMSO-d6) δ 9.57 (s, 1H), 7.05 (d, J = 8.3Hz, 1H), 6.52 (dd, J = 8.2, 2.4Hz, 1H), 6.43 (d, J = 2.4 Hz, 1 H), 2.85 (dd, J = 7.7, 6.6 Hz, 2H), 2.74 (m, 2H). EI-MS: 164.1 (M +), 136.0, 122.0, 107.0, 94.0, 66.0.

Example 4: Synthesis of 7-hydroxy-5-methylchroman-2-one

Analogously to Example 1, 5-methylresorcinol and acrylic acid are reacted.

Example 5: Synthesis of 5,7-dihydroxychroman-2-one

Analogously to Example 1, phloroglucinol and acrylic acid are reacted.

Example 6: Synthesis of 6-butyl-7-hydroxychroman-2-one

Analogously to Example 1, 4-butylresorcinol and acrylic acid are reacted.

Example 7: Synthesis of 6-cyclohexyl-7-hydroxychroman-2-one

Analogously to Example 1, 4-cyclohexylresorcinol and acrylic acid are reacted.

Example 8: Synthesis of 6-dodecyl-7-hydroxychroman-2-one

Analogously to Example 1, 4-dodecylresorcinol and acrylic acid are reacted.

Example 9: Synthesis of β-tert-octyl-T-hydroxychromanone

Analogously to Example 1, 4-tert-octyl-resorcinol and acrylic acid are reacted.

Example 10 Synthesis 6-Hydroxy-4,4,5,8-tetramethylchroman-2-one

Comparative Example from JP 2003321463.

To a yellow solution of 2,5-dimethyl-p-benzoquinone (18.4 mmol) in diethyl ether (75 ml) is added a suspension of sodium dithionite (23.4 mmol) in water (38 ml) and stirred. The biphasic reaction mixture is filtered and then separated the biphasic filtrate in a separating funnel, the aqueous phase is extracted twice with diethyl ether and the solvent distilled off. 1.1 g of 2,5-dimethyl-1,6-benzene-diol are obtained.

The 2,5-dimethyl-1, 6-benzene-diol (7.2 mmol) is dissolved in 3-methylcrotonic acid (7.2 mmol), then methanesulfonic acid (8 mL) is added and the brown solution at 60 ⁰ C heated , After about 6 hours, the brown solution is added to ice (about 50 g) and extracted several times with ethyl acetate. The solvent is distilled off. 800 mg of 6-hydroxy-4,4,5,8-tetramethylchroman-2-one are obtained. 1 H NMR (DMSO-d6) δ 9.15 (s, 1H), 6.60 (s, 1H), 2.59 (s, 2H), 2.21 (s, 3H), 2.10 (s, 3H), 1.36 (s, 6H)

Example 11: Synthesis of 6-hydroxy-4,4,5,7,8-pentamethylchroman-2-one

Comparative Example from JP 2003321463.

The trimethylhydroquinone (6.6 mmol) is dissolved in 3-methylcrotonic acid (6.7 mmol), then methanesulfonic acid (8 mL) is added and the brown solution was heated at 60 ⁰ C. After about 6 hours, the brown solution is added to ice (about 50 g) and extracted several times with ethyl acetate. The solvent is distilled off. 930 mg of 6-hydroxy-4,4,5,7,8-pentamethylchroman-2-one are obtained.

1 H NMR (DMSO-d6) δ 2.56 (s, 2H), 2.26 (s, 3H), 2.10 (s, 3H), 2.09 (s, 3H), 1.32 (s, 6H)

EI-MS: 234.1 (M +), 219.1 192.0

Example A:

Tyrosinase assay

The effect of the compounds I or Ia as skin whitening agent is tested by their ability to inhibit the enzyme tyrosinase and thus the

To prevent melanin synthesis.

The inhibitory activity of the compounds of formula I or Ia against tyrosinase is assessed using fungal tyrosinase and L-DOPA as substrate.

The compounds as described in Examples 1 to 3 and the

Comparative compounds of Examples 10 and 11, and L-Dopa are for Pre-incubated for 10 minutes at 25 ° C in phosphate buffer (pH 6.8) and then fungal tyrosinase (16U) (Fluka) is added. The optical density of the samples is measured at 470 nm against a negative control (without active ingredient). Kojic acid is tested as a tyrosinase reference, ie positive control.

The results are shown in the following table expressed in the IC50 value (the concentration of the test compound in which 50% of the tyrosinase activity is inhibited).

Table: Test results of the tyrosinase assay

Example B:

Depigmentation activity on the skin

The depigmenting activity of compounds of the formula I or Ia are determined in vitro by using a reconstituted human tanned

Epidermis model "(SkinEthic Laboratories).

The tanned epidermal tissues (11 days old, size 0.5 cm ² ) are treated daily for 4 days with 5 μl of a phosphate buffer solution of the compound 6-hexyl-7-hydroxychroman-2-one. In parallel, a negative control (epidermal tissue dosed with pure phosphate buffer only) and a positive control are prepared for comparison. All skin cultures are incubated at 37 ° C for 6 days. After the treatments, all epidermal tissues are examined by visual inspection for cell morphology and cell developability. In addition, the melanin content was quantified.

Example C: Preparations

In the following, exemplary formulations for cosmetic preparations are given which contain compounds according to Examples 1 to 3. Otherwise, the INCI names of the commercial compounds are given.

UV-Pearl, OMC stands for the preparation with the INCI name:

Water (for EU: Aqua), ethylhexyl methoxycinnamate, silica, PVP,

Chlorphenesin, BHT; This preparation is commercially available under the

Name Eusolex ^® UV Pearl ™ OMC available from Merck KGaA, Darmstadt.

The other UV pearls listed in the tables are each assembled analogously, with OMC being replaced by the specified UV filters.

TABLE 1 W / O emulsions (numbers in% by weight)

Table 1 (continued)

Continuation of Table 2:

Claims

claims

1. A preparation containing at least one compound of the formula I.

R ³

in which

R ¹ to R ^{3 are} each independently H, A, Y, OCOA or NHCOA,

R ^{4 is} H, A, Y ¹ , OCOA or NHCOA, R ² R ³ or R ¹ R ⁴ each, independently of one another, together denote methylenedioxy or ethylenedioxy,

A is each independently a saturated or unsaturated, linear, branched or cyclic alkyl group having 1 to 18 C atoms, which, by OH, O-alkyl, CO-alkyl, COOH, COO-alkyl, NH _2, NH-alkyl N (alkyl) ₂ , NHCO-alkyl, CONH ₂ , CONH-alkyl, sulfonate, OSi (alkyl) ₃ , F, Cl or Br may be substituted, Y is OH, OA, COA, COOH, COOA, NH ₂ , NHA, NA ₂ , NHCOA, CONH ₂ ,

CONHA, sulfonate, silyloxy, F, Cl ₁ or Br, Y "OA, COA, COOH, COOA, NH ₂ , NHA, NA ₂ , NHCOA, CONH ₂ , CONHA, sulfonate, OSi (A) ₃ , F, Cl , or Br means and

Alkyl is a saturated or unsaturated, linear, branched or cyclic alkyl group having 1 to 18 carbon atoms, or their salts or solvates.

2. Preparation according to claim 1, characterized in that in compounds of formula I ₁ R ² OH.

3. Preparation according to claim 1 or 2, characterized in that in compounds of the formula IR ^{4 is} H or A.

4. Preparation according to one or more of claims 1 to 3, characterized in that in compounds of formula IR ^{3 is} H.

5. Preparation according to one or more of claims 1 to 4 containing at least one carrier suitable for topical applications.

6. Preparation according to one or more of claims 1 to 5, characterized in that it contains one or more compounds of formula I in an amount of 0.01 to 20 wt .-%, based on the total weight of the preparation.

7. Preparation according to one or more of claims 1 to 6, characterized in that one or more antioxidants and / or one or more vitamins are included.

8. Preparation according to one or more of claims 1 to 7, characterized in that one or more UV filters are included.

9. Preparation according to one or more of claims 1 to 8, characterized in that at least one further compound with skin-whitening activity is included.

10. A preparation according to claim 9, characterized in that the further compound having skin-whitening activity is selected from hydroquinone, kojic acid, arbutin, aloesin or rucinol.

11. A process for the preparation of a preparation according to one or more of claims 1 to 10, characterized in that a or more compounds of the formula I according to one or more of claims 1 to 4 is mixed with at least one carrier suitable for topical applications.

12. Use of at least one compound of the formula I.

R ³

in which

R ¹ to R ^{3 are} each independently H, A, Y, OCOA or NHCOA,

Each independently of one another is a saturated or unsaturated, linear, branched or cyclic alkyl group having 1 to 18 C atoms, which is also denoted by OH, O-alkyl, CO-alkyl, COOH, COO-alkyl, NH ₂ , NH-alkyl, N (alkyl) ₂ , NHCO-alkyl, CONH ₂ , CONH-alkyl, sulfonate,

OSi (alkyl) ₃ , F, Cl or Br may be substituted, Y is OH, OA, COA, COOH, COOA, NH ₂ , NHA, NA ₂ , NHCOA, CONH ₂ , CONHA, sulfonate, silyloxy, F, Cl, or Br means Y'OA, COA, COOH ₁ COOA, NH ₂ , NHA, NA ₂ , NHCOA, CONH ₂ , CONHA, sulfonate, OSi (A) ₃ , F, Cl, or Br and

Alkyl is a saturated or unsaturated, linear, branched or cyclic alkyl group having 1 to 18 carbon atoms, or their salts or solvates or a preparation according to one or more of claims 1 to 10 for the lightening of human skin.

13. Use of at least one compound of the formula I in which

R ¹ to R ^{3 are} each independently H, A, Y, OCOA or NHCOA,

OSi (alkyl) ₃ , F, Cl or Br may be substituted, Y is OH, OA, COA, COOH, COOA ₁ NH ₂ , NHA, NA ₂ , NHCOA, CONH ₂ , CONHA, sulfonate, silyloxy, F, Cl, or Br means

Alkyl is a saturated or unsaturated, linear, branched or cyclic alkyl group having 1 to 18 carbon atoms, or their salts or solvates as a tyrosinase inhibitor.

14. Use of at least one compound of the formula I.

R ³

in which R ¹ to R ^{3 are} each independently H, A ₁ Y ₁ OCOA or NHCOA,

R ⁴ H ₁ A ₁ Y \ OCOA or NHCOA means

R ² R ³ or R ¹ R ⁴ each, independently of one another, together denote methylenedioxy or ethylenedioxy,

Each independently of one another is a saturated or unsaturated, linear, branched or cyclic alkyl group having 1 to 18 C atoms, which is also denoted by OH, O-alkyl, CO-alkyl, COOH, COO-alkyl, NH ₂ , NH-alkyl, N (alkyl) ₂ , NHCO-alkyl, CONH ₂ , CONH-alkyl, sulfonate, OSi (alkyl) ₃ , F ₁ Cl or Br may be substituted,

Y is OH, OA, COA, COOH, COOA, NH ₂ , NHA ₁ NA ₂ , NHCOA ₁ CONH ₂ , CONHA ₁ sulfonate, silyloxy, F, Cl, or Br, Y ¹ OA, COA, COOH, COOA, NH ₂ , NHA, NA ₂ , NHCOA, CONH ₂ , CONHA, sulfonate, OSi (A) ₃ , F, Cl, or Br, and alkyl denotes a saturated or unsaturated, linear, branched or cyclic alkyl group having 1 to 18 C atoms, or their salts or solvates or a preparation according to one or more of claims 1 to 10 for the prophylaxis and / or treatment of pigment disorders such as hyperpigmentation, freckles, age spots, sunspots and environmental aging of the skin.

15. Compounds of the formula Ia

in which

R ^{4 is} a linear or cyclic alkyl group having 4-18 carbon atoms and their salts and solvates.

16. A process for the preparation of compounds of formula Ia and their salts and solvates, characterized in that (a) a compound of formula IIa

wherein R ^{4 has} a meaning given in claim 15, reacted with acrylic acid, and

(b) optionally converting a basic or acidic compound of formula I into one of its salts or solvates by treatment with an acid or base.