EP1656364A1 - Chromen-4-one derivatives - Google Patents

Abstract

The invention relates to compounds that are selected from the compounds of formulas (Ia)-(Ic) and to their production and use in cosmetic and dermatological products.

Description

 Chromen-4-one derivatives

The present invention relates to chromene-4-one derivatives, their preparation and use for the care, preservation or improvement of the general condition of the skin or hair and for the prophylaxis against time and / or light-induced aging processes of the human skin or human hair and for the prophylaxis and / or treatment of skin diseases. The invention further relates to preparations with an effective. Content of such chromene-4-one derivatives.

Human skin is subject to certain aging processes, which are partly due to intrinsic processes (chronoaging) and partly to exogenous factors (environmental, e.g. photoaging). In addition, temporary or permanent changes in the skin appearance can occur, such as acne, oily or dry skin, keratoses, rosaceae, photosensitive, inflammatory, erythematous, allergic or autoimmune-reactive reactions such as dermatoses and photodermatoses.

The exogenous factors include, in particular, sunlight or artificial radiation sources with a comparable spectrum, as well as compounds that can arise from the radiation, such as undefined reactive photo products, which can also be radical or ionic. These factors also include cigarette smoke and the reactive compounds it contains, such as ozone, free radicals, for example that

Hydroxyl radical, singlet oxygen and other reactive oxygen or nitrogen compounds that interfere with the natural physiology or morphology of the skin.

The influence of these factors can lead to direct effects

Damage to the DNA of the skin cells and the collagen,

Elastin or glycosaminoglycan molecules of the extracellular matrix, which are responsible for the firmness of the skin. In addition, the signal transduction chains can be influenced, at the end of which there is the activation of matrix-degrading enzymes. Important representatives of these enzymes are the matrix metalloproteinases (MMPs, e.g. Collagenases, gelatinases, stromelysins), the activity of which is additionally regulated by TIMPs (tissue inhibitor of matrix metalloproteinases).

The consequences of the above Aging processes are thinning of the skin, weaker interlocking of the epidermis and dermis, reduction of

Cell count and the supplying blood vessels. This leads to the formation of fine lines and wrinkles, the skin becomes single and pigment disorders can occur.

The same factors also affect hair, where there is also one

Damage can come. The hair becomes brittle, less elastic and lackluster. The surface structure of the hair is damaged.

Cosmetic or dermatological care products with properties that counteract the described or comparable processes or that are intended to reduce or reverse the harmful effects are often characterized by the following specific properties - radical-catching, antioxidative, anti-inflammatory or moisturizing. Among other things, they prevent or reduce the activity of the matrix-degrading enzymes or regulate the new synthesis of

Collagen, elastin or proteoglycans.

The use of antioxidants or radical scavengers in cosmetic preparations is known per se. The use of antioxidant vitamin E in sunscreen formulations is common. However, the effect achieved here still falls far short of the hoped-for effect.

Vitamin. A and vitamin A derivatives, such as retinoic acid, retoinol and retinol esters, act on the differentiation of epithelial cells and are therefore used for the prophylaxis and treatment of numerous phenomena affecting the skin condition; e.g. the use against acne, psoriaris, age spots, skin discoloration and wrinkles is described. (see e.g. WO 93/19743, WO 02/02074).

However, retinol and

Derivatives described in the literature (eg WO 94/07462). Through this Side effects, the use of retinol is limited to narrowly limited areas, whereby an overdose must be avoided. There is therefore a need for active substances which have a retinol-like spectrum of activity, but which do not have the described side effects, or at least only have them in reduced form.

Because of the ever-increasing need for active substances for the preventive treatment of human skin and hair against aging processes and damaging environmental influences, it was the object of the present invention to provide new active substances which show the effects already mentioned, are sufficiently stable to oxidation and photostable and are easy to formulate should. The preparations thus produced should also have the lowest possible irritation potential for the skin, they should, if possible, have a positive effect on the water binding in the skin, maintain or increase the elasticity of the skin and thus promote smoothing of the skin. In addition, they should preferably produce a pleasant feeling on the skin when applied to the skin.

Surprisingly, it has now been found that certain chromene-4-one

Derivatives (chromone derivatives) are suitable as active ingredients with the profile described.

Applications of structurally related compounds are known from the literature:

The use of certain 2- (alkyl) carboxyl or 2- (alkyl) phenyl substituted chromene-4-one derivatives in combination with divalent zinc in pharmaceutical and cosmetic preparations is known from EP-A-0 304 802. The preparations are suitable for skin treatment, in particular for the treatment of dermatoses including atopic eczema.

EP-A-0424444 discloses the use of salts of chromoncarboxylic acid in cosmetics to combat skin aging. The compound shows a UV filtering effect and has in Animal experiments have the following effects: the proportion of bound lipids in the skin increases, the proportion of soluble collagen in the skin increases, the resistance of the skin to the effects of the fibroplatic proteases collagenase and elastase is increased.

US Pat. No. 6,019,992 discloses cosmetic preparations which contain 4-chromanone and which are suitable for the treatment of aged, dry or wrinkled skin. It is shown that 4-chromanone in keratinocyte cultures promotes cell differentiation and stimulates lipid production.

EP-A-1 216 692 discloses the use of 2-methyl-2- (β-carboxyethyl) chroman derivatives in cosmetic preparations. The preparations mentioned are particularly suitable for the prophylaxis against aging processes of skin and hair and for the prophylaxis against dry skin, wrinkling and pigment disorders.

Preparations for topical use, the chromone derivatives, e.g. Chromon, 7-Hydroxychromon, 7-Methoxychromon, 5,7-Dihydroxy-2-methyl-Chromon, 3-Methyl -2-butenyloxy-Chromon, 3-Acetyl-5,7-dihydroxy-

2-methylchromone, _{5-hydroxychromone.} n-pentyl-7-methoxychromone-2-carboxylate, n-undecyl-5-methoxychromone-2-carboxylate, 5-hydroxy-7-methoxy-2-methyl-chromone, 7-methoxy-chromon-2-carboxylic acid, n- Pentyl-chromon-2-carboxylic acid, 5-methoxychromone and chromone-2-carboxylic acid, are known from Japanese patent application JP 05/301813. The chromone derivatives act as skin-compatible tyrosinase inhibitors, which reduce hyperpigmentation of the skin.

Japanese patent application JP 09/188608 describes the use of substituted chromone derivatives, in particular 5,7-

Dihydroxychromones, 7-methoxychromones, 5-hydroxy-7-methoxy-2-methyl-chromon and 5-hydroxy-2-methyl-chromon, known as an active ingredient against gray hair. The effect is attributed to the activation of the color pigment-forming cells and the increase in melanogenesis. An agent against skin aging containing chromone derivatives which are substituted in position 2 with C ₁₅ alkyl and in position 7 have H, OH or alkoxy substitution in combination with aminopropanol derivatives is known from JP 10/194919.

Cosmetic preparation containing substituted chromone derivatives, e.g. 2- (l-ethylpentyl) chromone, 5,7-dihydroxychromones, 7-methoxychromones, 5-hydroxy-7-methoxy-2-methyl-chromone and 5-hydroxy-2-methyl-chromone and aromatic compounds with a melting point of -10 ° C or above are known from JP 10/114640. The chromone derivative makes it easier to incorporate the aromatic compound into the cosmetic formulation.

A first subject of the present invention are therefore compounds selected from the compounds of the formulas la-lc

in which

R ¹ and R ^{2 may be the} same or different and are selected from

- H, -C (= 0) -R ⁷ , -C (= 0) -OR ⁷ ,

straight-chain or branched d- to C ₂ o -alkyl groups,

straight-chain or branched C ₃ to C ₂₀ alkenyl groups, straight-chain or branched C to C ₂ o-hydroxyalkyl groups, where the hydroxy group can be bound to a primary or secondary carbon atom of the chain and the alkyl chain can also be interrupted by oxygen, and or

C ₃ to Cio-cycloalkyl groups and / or C ₃ to C ₁₂ cycloalkenyl groups, where the rings can also be bridged by - (CH ₂ ) _n - groups with n = 1 to 3,

R ³ stands for H or straight-chain or branched C to C2 ₀ -

alkyl groups,

R ⁴ stands for H or OR ⁸ ,

R ⁵ and R ^{6 may be the} same or different and are selected from

- -H. -OH, straight-chain or branched C to C ₂ o-alkyl groups,

straight-chain or branched C ₃ to C ₂ o-alkenyl groups,

- Straight-chain or branched d- to C ₂ o-hydroxyalkyl groups, where the hydroxy group can be bound to a primary or secondary carbon atom of the chain and the alkyl chain can also be interrupted by oxygen and R ⁷ represents H, straight or branched C ₂ to C o alkyl groups, a polyhydroxy compound, such as preferably an Ascorbinsääurerest or glycosidic residues, and R ⁸ is H or straight or branched C _t - to C 20 alkyl groups, wherein one the radicals R ¹ or R ² for H or a straight-chain or branched Cι. ₂ o-alkyl group and the other radical stands for - C (= 0) -R ⁷ , -C (= 0) -OR ⁷ or a straight-chain or branched C to C ₂ o-alkyl group, and at least one of the radicals R ³ or R ^{4 is} not H if R ⁷ is H.

For the purposes of the present invention, the term “compound of the formula Ia-m” also includes the salts of the respective compounds of the formula Ia-m. The preferred salts include in particular alkali metal and alkaline earth metal salts and ammonium salts, but especially sodium - and potassium salts.

According to the invention, particular preference is given to compounds of the formula Ia, which is a compound selected from the compounds having the formulas Id-Im:

In one variant of the invention, compounds which are characterized in that at least 2 of the substituents R ¹ , R ² , R ⁴ -R ^{6 are} different from H are particularly preferred.

It is further preferred according to the invention if the compounds are characterized in that a substituent from R ¹ and R ^{2 is} - C (= 0) -R ⁷ or -C (= 0) -OR ⁷ .

With regard to the desired property profile, it has also proven to be preferred if the compounds are characterized in that R ³ is H and R ⁴ is OH, preferably at least one of the radicals R ⁵ and R ^{δ being} OH.

In a further group of compounds preferred according to the invention, R ⁵ and R ^{6 are} H.

The present invention furthermore relates to preparations comprising at least one compound of the formula Ia-m with radicals as defined above, and at least one further skin-care product

Ingredient and at least one carrier suitable for topical applications and the use of the above-mentioned compounds for the care, preservation or improvement of the general condition of the skin or hair.

Preferred uses according to the invention of the compounds of the formula Ia-m or of preparations comprising at least one compound of the formula Ia-m are in particular the use for prophylaxis against time and / or light-induced aging processes of human skin or human hair, in particular for

Prophylaxis against dry skin, wrinkling and / or

Pigment disorders, and / or for reducing or preventing damaging effects of UV rays on the skin, and for prophylaxis against or reduction of skin imperfections, such as wrinkles, fine lines, rough skin or large-pored skin. Preferred uses according to the invention of the compounds of the formula Ia-m or of preparations comprising at least one compound of the formula Ia-m are furthermore the use for the prophylaxis and / or prevention of premature skin aging, in particular for the prophylaxis and / or prevention of light or aging-related

Wrinkling of the skin, for reducing pigmentation and keratosis actinica and for the prophylaxis and / or treatment of all diseases which are associated with normal aging or light-related aging of the skin, and for the prophylaxis and / or treatment of skin diseases which are associated with a Disorder of

Keratinization, which affects differentiation and cell proliferation, in particular for the treatment of acne vulgaris, acne comedonica, polymorphic acne, acne rosaceae, nodular acne, acne conglobata, age-related acne, the side effects of acne , such as acne solaris, medication-related acne or professional acne, for the treatment of other disorders of keratinization, in particular ichthyosis, ichtyosiform conditions, Darrier's disease, keratosis palmoplantaris, leukopiasias, leukoplasiform conditions, the Skin and mucous membrane braiding (Buccal) (lying), for

Treatment of other skin disorders related to a keratinization disorder that have an inflammatory and / or immunoallergic component, and in particular all forms of psoriasis that affect the skin, mucous membranes and fingers and toenails, and psoriatic rheumatism and skin atopies, such as eczema or respiratory atopy or hypertrophy of the gums, as well as for the prophylaxis and / or treatment of all benign or malignant growths of the dermis or epidermis, which may be of viral origin, such as verruca vulgaris. Veruca plana, Epidermodysplasia verrueiformis, oral

Papillomatosis, Papillo-matosis florida, and the growths that can be caused by UV radiation, in particular the epithelioma basocellular and epithelioma spinocellulare. The use of the compounds of the formula Ia-m for the preparation of preparations suitable for the uses indicated above is also the object of the present invention.

The preparations are usually either topically applicable preparations, for example cosmetic or dermatological formulations, or foods or food supplements. In this case, the preparations contain a cosmetically or dermatologically or food-compatible carrier and, depending on the desired property profile, optionally further suitable ingredients.

The use according to the invention of chromene-4-one derivatives of the formula la-m in preparations offers, inter alia, protection against damage caused by UV radiation or reactive compounds

Processes are caused directly or indirectly, such as B. skin aging, loss of skin moisture, loss of skin elasticity, the formation of wrinkles or wrinkles or pigment disorders or age spots.

Furthermore, the present invention relates to the use of the above. Preparations for the prevention of undesirable changes in the complexion, e.g. Acne or oily skin, keratosis, photosensitive, inflammatory, erythrematous, allergic or autoimmune reactive reactions.

However, the compounds or preparations according to the invention preferably also serve to soothe sensitive and irritated skin, for preventive regulation of the synthesis of collagen, hyaluronic acid, elastin, stimulation of DNA synthesis, in particular in the case of deficient or hypoactive skin conditions, regulation of transcription and translation of matrix-degrading enzymes , in particular the MMPs, increasing cell renewal and skin regeneration, increasing the skin's own protective and repair mechanisms for DNA, lipids and / or proteins. Compounds according to formula la-m which are preferably to be used are characterized in that R ³ stands for H and R ⁴ stands for OH since the active potential of representing this class of invention in the abovementioned sense is particularly high. If at least one of the radicals R ⁵ and R ⁶ additionally represents OH, these preferred compounds have, in addition to the properties mentioned above, an antioxidant potential. Therefore, they can act as an antioxidant in preparations.

Other compounds of formula la-m to be used preferably are characterized in that R ⁵ and R ^{6 are} H. In this case, the residues R ³ and R ^{4 are} freely accessible, which, as is assumed, is advantageous for the interaction with enzymes involved in the effects mentioned.

Compounds of the formula Ia-m which are likewise preferably to be used are characterized in that one of the radicals R ¹ or R ^{2 is} H and the other radical is -C (= 0) -R ⁷ , -C (= 0) -OR ⁷ or a straight-chain or branched C to C ₂ o-alkyl group.

In addition, compounds to be used according to the invention have advantages when incorporated into the preparations:

- Mono- and / or oligoglycosyl residues improve the water solubility of the compounds to be used according to the invention;

straight-chain or branched C to C ₂ o-alkoxy groups, especially the long-chain alkoxy functions, such as ethylhexyloxy groups, increase the oil solubility of the compounds; ie the hydrophilicity or lipophilicity of the compounds according to the invention can be controlled via a suitable selection of the substituents.

In particular, mono- or oligosaccharide residues can be used as glycoside residues. Hexosyl radicals are preferred, in particular

Ramnosyl residues and glucosyl residues. However, other hexosyl radicals, for example allosyl, altrosyl, galactosyl, gulosyl, idosyl, mannosyl and talosyl, may also be used advantageously. It may also be advantageous to use pentosyl residues. The glycosyl radicals can be connected to the base body in an α- or β-glycosidic manner. A preferred one Disaccharide is, for example, 6-0- (6-deoxy-α-L-mannopyranosyl) -ß-D-glucopyranoside.

In likewise preferred embodiments of the invention, however, the preparations according to the invention can also contain poorly or insoluble compounds of the formula Ia-m in the preparation matrix. In this case, the compounds are preferably in dispersed form in the cosmetic preparation.

According to the invention, the compounds of the formula Ia-m are typically used in

Amounts of 0.01 to 20% by weight, preferably in amounts of 0.1% by weight to 10% by weight and particularly preferably in amounts of 1 to 8% by weight. It is no problem for the person skilled in the art to select the amounts appropriately depending on the intended action of the preparation.

The protective action against oxidative stress or against the action of radicals can therefore be further improved if the preparations contain one or more further antioxidants, it being no problem for the person skilled in the art to select suitable antioxidants which act quickly or with a delay.

In a preferred embodiment of the present invention, at least one further skin-care ingredient is one or more antioxidants and / or vitamins.

For the reasons mentioned above, it is particularly preferred if the preparation does not contain a retinol derivative.

There are many well-known and proven substances known from the literature that can be used as antioxidants, e.g. Amino acids (e.g.

Glycine, histidine, tyrosine, tryptophan) and their derivatives, imidazoles (e.g. urocanic acid) and their derivatives, peptides such as D, L-camosine, D-

Carnosine, L-camosine and their derivatives (e.g. anserine), carotenoids, carotenes (e.g. α-carotene, ß-carotene, lycopene) and their derivatives,

Chlorogenic acid and its derivatives, lipoic acid and its derivatives (e.g. Dihydrolipoic acid), aurothioglucose, propylthiouracil and other thiols (e.g. thioredoxin, glutathione, cysteine, cystine, cystamine and their glycosyl, N-acetyl, methyl, ethyl, propyl, amyl, butyl and lauryl, palmitoyl, , Oleyl, γ-linoleyl, cholesteryl and glyceryl esters) as well as their salts, dilauryl thiodipropionate, distearyl thiodipropionate, thiodipropionic acid and their derivatives (esters, ethers, peptides, lipids, nucleotides, nucleosides and salts) as well as sulfoximine compounds (e.g. buthioninsulfonine sulfoximine, homocystone sulfoximine, homocystone sulfonimine, homocystone sulfoximine, homocystone sulfone imine, homocystone sulfone imine, homocystone sulfone imine, homocystone sulfone imine, homocystone sulfone imine, homocystone sulfone imine, homocystone sulfonimine, Penta-, hexa-, heptathionin-sulfoximine) in very low tolerable doses (e.g. pmol to μmol / kg), also (metal) chelators (e.g. α-hydroxy fatty acids, palmitic acid, phytic acid, lactoferrin), α-hydroxy acids ( e.g. 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 (e.g. As corbyl palmitate, magnesium ascorbyl phosphate, ascorbyl acetate), tocopherols and derivatives

(eg vitamin E acetate) and coniferyl benzoate of benzoin, rutinic acid and its derivatives, α-glycosylrutin, ferulic acid, furfurylidene glucitol, carnosine, butylated hydroxytoluene, butylated hydroxyanisole, nordohydroguaretic acid, trihydroxybutrophenon, harnose and mannicinitin derivatives, quernicinitinin, quinicinitinin, quinicinitinin, quinicinitinin, quinicinitinin, quinicinitinin, quinitinitinin and their derivatives, zinc and its derivatives (e.g.

ZnO, ZnS0 ₄ ), selenium and its derivatives (eg selenium methionine), stilbene and their derivatives (eg stilbene oxide, trans-stilbene oxide).

Mixtures of antioxidants are also suitable for use in the cosmetic preparations according to the invention. Known and commercially available mixtures are, for example, mixtures containing lecithin, L - (+) - ascorbyl palmitate and citric acid (e.g.

(e.g. Oxynex ^® AP), natural tocopherols, L - (+) - ascorbyl palmitate, L - (+) -

Ascorbic acid and citric acid (e.g. Oxynex ^® K LIQUID), tocopherol extracts from natural sources, L - (+) - ascorbyl palmitate, L - (+) - ascorbic acid and citric acid (e.g. Oxynex ^® L LIQUID), DL- tocopherol,

L - (+) - ascorbyl palmitate, citric acid and lecithin (e.g. Oxynex ^® LM) or

Butylated hydroxytoluene (BHT), L - (+) - ascorbyl palmitate and citric acid (e.g.

Oxynex ^® 2004). Such antioxidants are usually found in compounds of the formula Ia-m in such compositions Ratios in the range from 1000: 1 to 1: 1000, preferably used in amounts of 100: 1 to 1: 100.

The preparations according to the invention can contain vitamins as further ingredients. Vitamins and vitamin derivatives are preferably selected from vitamin B, thiamine chloride hydrochloride (vitamin Bt), riboflavin (vitamin B ₂ ), nicotinic acid amide, vitamin C (ascorbic acid), vitamin D, ergocalciferol (vitamin D ₂ ), vitamin E, DL-tocopherol , Tocopherol E acetate, tocopherol hydrogen succinate, vitamin Ki, esculin (vitamin P active ingredient), thiamine (vitamin Bi), nicotinic acid (niacin), pyridoxine,

Pyridoxal, pyridoxamine, (vitamin B ₆ ), pantothenic acid, biotin, folic acid and cobalamin (vitamin B ₁₂ ) in the cosmetic preparations according to the invention, particularly preferably vitamin C and its derivatives, DL-α-tocopherol, tocopherol E-acetate, nicotinic acid , Pantothenic acid and biotin. Vitamins are combined with the

Formula la-m is usually used in ratios in the range from 1000: 1 to 1: 1000, preferably in amounts from 100: 1 to 1: 100.

Among the phenols with an antioxidative effect, the polyphenols, some of which occur as natural substances, are particularly interesting for applications in the pharmaceutical, cosmetic or nutritional field. For example, they mainly show as

Plant dyes often have an antioxidant potential for known flavonoids or bioflavonoids. K. Lemanska deals with effects of the substitution pattern of mono- and dihydoxyflavones,

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 with an OH group adjacent to the keto function or

OH groups in the 3'4'- or 6.7- or 7.8-position have antioxidative properties, while other mono- and dihydroxyflavones sometimes have no antioxidative properties.

Quercetin (cyanidanol, cyanidenolone 1522, meletin,

Sophoretin, Ericin, 3,3 ', 4', 5,7-Pentahydroxyflavon) mentioned as a particularly effective antioxidant (e.g. CA.Rice-Evans, N.J. Miller,

G. Paganga, Trends in Plant Science 1997, 2 (4), 152-159). K. Lemanska, H. Szymusiak, B. Tyrakowska, R. Zielinski, AEMF Soffers, IMCM Rietjens; Free Radicai Biology & Medicine 2001, 31 (7), 869-881 investigate the pH dependence of the antioxidant activity of hydroxyflavones. Quercetin shows the highest activity of the examined structures over the entire pH range.

Suitable antioxidants are also compounds of the formula II

where R ¹ to R ^{10 can be the} same or different and are selected from - H - OR ¹¹ - straight-chain or branched C to C ₂ o-alkyl groups, - straight-chain or branched C ₃ - to C ₂ o-alkenyl groups, - straight-chain or branched C to C ₂ o-hydroxyalkyl groups, where the hydroxy group can be bound to a primary or secondary carbon atom of the chain and the alkyl chain can also be interrupted by oxygen, and / or - C ₃ - to Cio-cycloalkyl groups and / or C ₃ - to C-ι ₂ - cycloalkenyl groups, where the rings can also be bridged by - (CH2) _n - groups with n = 1 to 3, where all OR ^{11 are} independently - OH - straight-chain or branched d to C ₂ o-alkyloxy groups, straight-chain or branched C ₃ to C 20 alkenyloxy groups, straight-chain or branched Cr to C ₂ o -hydroxyalkoxy groups, where the hydroxy group (s) can be bonded to a primary or secondary carbon atoms of the chain and the alkyl chain can also be interrupted by oxygen, and / or - C ₃ - to Cio- Cycloalkyloxy groups and / or C ₃ - to C ₁₂ - cycloalkenyloxy groups, where the rings can also be bridged by - (CH ₂ ) n groups with n = 1 to 3 and / or, - mono- and / or oligoglycosyl radicals with which Provided that at least 4 radicals from R ¹ to R ⁷ stand for OH and that there are at least 2 pairs of adjacent groups -OH in the molecule, or R ² , R ⁵ and R ⁶ for OH and the radicals R ¹ , R ³ , R ⁴ and R ^{7 "10} stand for H, as described in the older German patent application DE 10244282.7.

Advantages of the compositions according to the invention containing at least one antioxidant are in addition to those mentioned above

Advantages in particular the antioxidant effect and the good skin tolerance. In addition, preferred of the compounds described here are colorless or only slightly colored and thus do not lead to discoloration of the preparations or only to a minor extent. Of particular advantage is the special activity profile of the compounds of the formula lam I, which in the DPPH assay has a high capacity to trap radicals (EC ₅₀ ), a time-delayed action (TECSO> 120 min) and thus a medium to high antiradical action Efficiency (AE) expressed. In addition, the compounds of the formula Ia-m I combine antioxidative properties in the molecule with UV absorption in the UV-A and / or -B range.

Preparations containing at least one are therefore preferred

Compound of the formula II, which is characterized in that at least two adjacent radicals of the radicals R ¹ to R ⁴ are OH and at least two adjacent radicals of the radicals R ⁵ to R ⁷ are OH. Particularly preferred preparations contain at least one

Compound of formula II, which is characterized in that at least three adjacent residues of the residues R ¹ to R ⁴ stand for OH, wherein the residues R ¹ to R ³ preferably stand for OH.

So that the compounds of formula la-m can develop their positive effect on the skin particularly well, it may be preferred

To allow compounds of the formula la-m to penetrate into deeper skin layers. There are several ways to do this. On the one hand, the compounds of the formula Ia-m can have sufficient lipophilicity to be able to penetrate through the outer skin layer into epidermal layers. As a further possibility, corresponding transport agents, for example liposomes, can also be provided in the preparation, which allow the compounds of the formula Ia-m to be transported through the outer skin layers. Finally, a systemic transport of the compounds of the formula Ia-m is also conceivable. The preparation is then designed, for example, so that it is for an oral

Gift is suitable.

It is also advantageous to present the compounds of formula II in encapsulated form, e.g. B. encapsulated as cellulose or chitin, encapsulated in gelatin or wax matrices or with cyclodextrins.

It is believed that preferred compounds of formula la-m also act as enzyme inhibitors. They presumably inhibit protein kinases, elastase, aldose reductase and hyaluronidase, and therefore make it possible to maintain the integrity of the basic substance of vascular shells. Furthermore, they presumably do not specifically inhibit catechol-O-methyltransferase, which increases the amount of available catecholamines and thereby the vascular strength. Furthermore, they presumably inhibit AMP phosphodiesterase, which means that the substances have a potential to inhibit platelet aggregation.

Because of these properties, the preparations according to the invention are generally suitable for immune protection and for protecting DNA and RNA. The preparations are particularly suitable for protecting DNA and RNA against oxidative attacks, against radicals and against

Damage from radiation, especially UV radiation. Another The advantage of the preparations according to the invention is cell protection, in particular the protection of Langerhans cells from damage caused by the above-mentioned influences. All of these uses or the use of the compounds of the formula Ia-m for the preparation of appropriately usable preparations are expressly also

Object of the present invention.

In particular, preferred compositions according to the invention are also suitable for the treatment of skin diseases which are associated with a keratinization disorder which relates to differentiation and cell proliferation, in particular for the treatment of acne vulgaris, acne comedonica, polymorphic acne, acne rosaceae, nodular acne, acne conglobata, age-related acne, acne as a side effect, such as acne solaris, medication-related acne or professional acne

Treatment of other disorders of keratinization, in particular ichthyoses, ichtyosi-like conditions, Darrier's disease, keratosis palmoplantaris, leukopiasias, leukoplasiform conditions, skin and mucous membrane lichen (buccal) (lying), for the treatment of other skin diseases who with a disorder of

Keratinization are related and have an inflammatory and / or immunoallergic component and in particular all forms of psoriasis, which affect the skin, mucous membranes and fingers and toenails, and psoriatic rheumatism and skin atopies, such as eczema or respiratory atopy or else

Gum hypertrophy, which compounds can also be used in some inflammation that is not related to keratinization disorder, for the treatment of any benign or malignant growths of the dermis or epidermis that may be of viral origin, such as verruca vulgaris. Veruca plana, Epidermodysplasia verrueiformis, oral papillomatosis, papillomatosis florida, and the growths that can be caused by UV radiation, in particular the epithelioma basocellular and epithelioma spinocellular, for the treatment of other skin diseases, such as dermatitis bullosa and collagen diseases in question

Treatment of certain eye diseases, especially the corneal Diseases to correct or combat light-related and aging-related skin aging, to reduce pigmentation and keratosis actinica and to treat all diseases related to normal aging or light-related aging to prevent or prevent

Healing of wounds / scars of the atrophies of the epidermis and / or dermis, which are caused by locally or systemically applied corticosteroids and all other types of skin atrophy, for the prevention or treatment of disorders of wound healing, for the prevention or correction of stretch marks or also to

Promotion of wound healing, to combat disorders of taig production, such as hypersebhorrhea in acne or simple seborrhea, to combat or prevent cancerous conditions or pre-cancerous conditions, especially promyelocytic leukemia, to treat inflammatory diseases such as arthritis, to treat all virus-related Diseases of the skin or other areas of the body, for the prevention or treatment of alopecia, for the treatment of skin diseases or diseases of other areas of the body with an immunological component, for the treatment of cardiovascular diseases, such as arteriosclerosis or high blood pressure, and of insulin-independent diabetes, for the treatment of skin problems caused by UV radiation.

Preparations which are particularly preferred according to the invention contain, in addition to the compounds of the formula, also UV filters.

When using the dibenzoylmethane derivatives, which are particularly preferred as UV-A filters, in combination with the compounds of the formula Ia-m, there is an additional advantage: The UV-sensitive dibenzoylmethane derivatives are caused by the presence of the

Compounds of the formula la-m additionally stabilized. The present invention therefore furthermore relates to the use of the compounds of the formula Ia-m for the stabilization of

Dibenzoylmethane derivatives in preparations. In principle, all UV filters can be used in combination with the compounds of the formula Ia-m according to the invention. Those UV filters whose physiological harmlessness has already been proven are particularly preferred. Both for UVA and UVB filters there are many well-known and proven substances from the specialist literature, e.g.

Benzylidene camphor derivatives such as 3- (4 ^' -methylbenzylidene) -dl-camphor (e.g. Eusolex® 6300), 3-benzylidene camphor (e.g. Mexoryl® SD), polymers of N - {(2 and 4) - [(2-oxobom-3- ylidene) methyl] benzyl} acrylamide (e.g. Mexoryl® SW), N, N, N-trimethyl-4- (2-oxobom-3-ylidene methyl) anilinium methyl sulfate

(e.g. Mexoryl® SK) or (2-oxoborn-3-ylidene) toluene-4-sulfonic acid (e.g. Mexoryl® SL),

Benzoyl- or dibenzoylmethanes such as 1- (4-tert-butylphenyl) -3- (4-methoxyphenyl) propane-1, 3-dione (e.g. Eusolex® 9020) or 4-

Isopropyldibenzoylmethane (e.g. 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 the isomers (e.g. Neo Heliopan® E 1000),

Salicylate derivatives such as 2-ethylhexyl salicylate (e.g. Eusolex® OS), 4-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, 4-

(Dimethylamino) 2-ethylhexyl benzoate (e.g. Eusolex® 6007), ethoxylated 4-aminobenzoate (e.g. Uvinul® P25),

Phenylbenzimidazole sulfonic acids, such as 2-phenylbenzimidazole-5-sulfonic acid and their potassium, sodium and triethanolamine salts (e.g. Eusolex®

232), 2,2- (1,4-phenylene) bisbenzimidazole-4,6-disulfonic acid or their Salts (eg Neoheliopan® AP) or 2,2- (1,4-phenylene) bisbenzimidazole-6-sulfonic acid;

and other substances such as - 2-cyano-3,3-diphenylacrylic acid 2-ethylhexyl ester (e.g. Eusolex® OCR),

- 3,3 ^' - (1,4-phenylenedimethylene) -bis- (7,7-dimethyl-2-oxobicyclo- [2.2.1] hept-1-ylmethanesulfonic acid as well as their salts (e.g. 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 (e.g.

Uvinul®UVA Plus, from BASF).

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

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

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 (e.g. silatrizole ^® ),

- 4,4 '- [(6- [4 - ((1, 1-dimethylethyl) aminocarbonyl) phenylamino] -1,3,5-triazine-2,4-diyl) diimino] bis (2-ethylhexyl benzoate) (e.g. Uvasorb ^® HEB),

- α- (Trimethylsilyl) -ω- [trimethylsilyl) oxy] poly [oxy (dimethyl [and about 6% methyl [2- [p- [2,2-bis (ethoxycarbonyl] vinyl] phenoxy] -1-methyleneethyl] and about 1.5% methyl [3- [p- [2,2-bis (ethoxycarbonyl) vinyl) phenoxy) propenyl) and 0.1 to 0.4% (methylhydrogenjsilylene]] (n * 60) (CAS No. 207 574-74-1)

- 2,2'-methylene-bis- (6- (2H-benzotriazol-2-yl) -4- (1, 1, 3,3-tetramethylbutyl) phenol) (CAS No. 103 597-45- 1 )

- 2,2 '- (1, 4-phenylene) bis- (1 H-benzimidazόl-4,6-disulfonic acid, monosodium salt) (CAS No. 180 898-37-7) and - 2,4-bis - {[4- (2-ethylhexyloxy) -2-hydroxyl] phenyi} -6- (4-methoxyphenyl) - 1, 3,5-triazine (CAS No. 103 597- 45-, 187 393-00-6).

- 4,4 ^' - [(6- [4 - ((1, 1-dimethylethyl) aminocarbonyl) phenylamino] -1, 3,5-triazine-2,4-diyl) diimino] bis (2-ethylhexyl benzoate) (e.g. Uvasorb ^® HEB),

Other suitable UV filters are also methoxy flavones according to the older German patent application DE 10232595.2.

Organic UV filters are generally incorporated into cosmetic formulations in an amount of 0.5 to 20 percent by weight, preferably 1-15%.

Conceivable inorganic UV filters are those are possible from the group of titanium dioxides, such as coated titanium dioxide (for example Eusolex® T-2000, Eusolex ^® T-AQUA), zinc oxides (eg Sachtotec.RTM), iron oxides and also cerium oxides. These inorganic UV filters are generally incorporated into cosmetic preparations in an amount of 0.5 to 20 percent by weight, preferably 2 to 10%.

Preferred compounds with UV-filtering properties are 3- (4 ^' -

Methylbenzylidene) dl camphor, 1- (4-tert-butylphenyl) -3- (4-methoxyphenyl) - pro-pan-1, 3-dione, 4-isopropyldibenzoylmethane, 2-hydroxy-4-methoxybenzophenone , Octyl methoxycinnamate, 3,3,5-trimethyl-cyclo-hexyl salicylate, 2-ethyl-hexyl 4- (dimethylamino) benzoate, 2-ethylhexyl 2-cyano-3,3-di-phenyl-acrylate, 2-phenyl-benzimidazole-5-sulfonic acid and its potassium, sodium and triethanolamine salts.

The protective effect against harmful effects of UV radiation can be optimized by combining one or more compounds of the formula lam with further UV filters.

Optimized compositions can, for example, combine the organic UV filter 4'-methoxy-6-hydroxyflavon with 1- (4-tert-

Butylphenyl) -3- (4-methoxyphenyl) propane-1, 3-dione and 3- (4 ^' - methylbenzylidene) dl camphor contain. With this combination you get a broadband protection that can be supplemented by adding inorganic UV filters such as titanium dioxide microparticles.

All of the UV filters mentioned can also be used in encapsulated form. In particular, it is advantageous to use encapsulated organic UV filters. The individual advantages are as follows:

- 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 oily impression, which is often perceived as unpleasant, is prevented when the preparation containing the hydrophobic UV filter is applied.

- Certain UV filters, especially dibenzoylmethane derivatives, show only a reduced photostability in cosmetic preparations. By

Encapsulation of these filters or of compounds that impair the photostability of these filters, such as cinnamic acid derivatives, can increase the photostability of the entire preparation.

- In the literature, skin penetration through organic UV filters and the associated potential for irritation when applied directly to human skin are repeatedly discussed. This effect is prevented by the encapsulation of the corresponding substances proposed here.

- Generally, encapsulation of individual UV filters or other ingredients can cause preparation problems caused by the interaction of individual

Preparation components arise among one another, as crystallization processes, precipitations and agglomerate formation are avoided, since the interaction is prevented.

It is therefore preferred according to the invention if one or more of the above-mentioned UV filters are in encapsulated form. It is advantageous if the capsules are so small that they cannot be observed with the naked eye. To achieve the above-mentioned effects, it is also necessary that the capsules are sufficiently stable and do not release the encapsulated active ingredient (UV filter) into the environment or only to a small extent. Suitable capsules can have walls made of inorganic or organic polymers. For example, US 6,242,099 B1 describes the production of suitable capsules with walls made of chitin, chitin derivatives or polyhydroxylated polyamines. Capsules to be used particularly preferably according to the invention have walls which can be obtained by a SolGel process, as described in the applications WO 00/09652, WO 00/72806 and WO 00/71084. Again, capsules are preferred, the walls of which are made of silica gel (silica; undefined silicon oxide hydroxide). The production of corresponding capsules is known to the person skilled in the art, for example from the cited patent applications, the content of which expressly belongs to the subject of the present application.

The capsules in the 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 skin-protecting or skin-care active ingredients can in principle be all active ingredients known to the person skilled in the art.

In one embodiment of the present invention, particularly preferred active ingredients are pyrimidinecarboxylic acids and / or aryloximes.

Pyrimidinecarboxylic acids occur in halophilic microorganisms and play a role in the osmoregulation of these organisms

(E. A. Galinski et al., Eur. J. Biochem., 149 (1985) pages 135-139). Among the pyrimidinecarboxylic acids, ectoin ((S) -1, 4,5,6-tetrahydro-2-methyl-4-pyrimidinecarboxylic acid) and hydroxyectoin ((S, S) -

1, 4,5,6-tetrahydro-5-hydroxy-2-methyl-4-pyrimidinecarboxylic acid and their

To name derivatives. These compounds stabilize enzymes and others

Biomolecules in aqueous solutions and organic solvents.

Furthermore, they particularly stabilize enzymes against denaturing Conditions such as salts, extreme pH, surfactants, urea, guanidinium chloride and other compounds.

Ectoin and ectoin derivatives such as hydroxyectoin can advantageously be used in medicinal products. In particular, hydroxyectoin can be used for

Manufacturing a drug used to treat skin disorders. Other areas of application of the hydroxyectoin and other ectoin derivatives are typically in areas in which e.g. Trehalose is used as an additive. Ectoin derivatives, such as hydroxyectoin, can be used as a protective substance in dried yeast and bacterial cells

Find 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.

Cosmetic applications include in particular the use of ectoin and ectoin derivatives for the care of aged, dry or irritated skin. For example, European patent application EP-A-0 671 161 describes in particular that ectoin and hydroxyectoin in cosmetic preparations such as powders, soaps, surfactant-containing cleaning products, lipsticks, blushes, make-ups, skin care creams and

Sun protection preparations are used.

A pyrimidine carboxylic acid according to formula II below is preferably used,

wherein R ^{1 is} H or C1-8-alkyl, R ^{2 is} H or C1-4-alkyl and R ³ , R ⁴ , R ⁵ and R ^{6 are} each independently a group from the group H, OH, NH ₂ and are C1-4 alkyl. Pyrimidinecarboxylic acids in which R ^{2 is} a methyl or an ethyl group and R ¹ or R ⁵ and R ^δ H are preferably used. The pyrimidinecarboxylic acids ectoin ((S) -1, 4,5,6-tetrahydro-2-methyl-4-pyrimidinecarboxylic acid) and hydroxyectoin ((S, S) -1, 4,5,6- Tetrahydro-5-hydroxy-2-methyl-4-pyrimidine-carboxylic acid) used. The preparations according to the invention preferably contain pyrimidinecarboxylic acids of this type in amounts of up to 15% by weight. The pyrimidinecarboxylic acids are preferably used in ratios of 100: 1 to 1: 100 to the compounds of the formula Ia-m, with ratios in the range 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 German Offenlegungsschrift DE-A-41 16 123. Preparations which contain 2-hydroxy-5-methyllaurophenonoxime are therefore suitable for the treatment of skin diseases which are associated with inflammation. It is known that such preparations e.g. can be used to treat psioriasis, various forms of eczema, irritative and toxic dermatitis, UV dermatitis and other allergic and / or inflammatory diseases of the skin and the appendages of the skin. Preparations according to the invention which, in addition to the compound of the formula Ia-m, additionally contain an aryioxime, preferably 2-hydroxy-5-methyllaurophenone oxime, have surprising anti-inflammatory properties. The preparations preferably contain 0.01 to 10% by weight of the aryl oxime, it being particularly preferred if the preparation contains 0.05 to 5% by weight aryioxime.

All compounds or components that can be used in the preparations are either known and commercially available or can be synthesized by known methods. The Preparation of the new compounds according to formula la-m is described below.

The one or more compounds of the formula Ia-m can be incorporated into cosmetic or dermatological preparations in the customary manner. Preparations are suitable for external use, for example as a cream, lotion, gel, or as a solution which can be sprayed onto the skin. Dosage formulas such as capsules, coated tablets, powders, tablet solutions or solutions are suitable for internal use.

As a form of application of the preparations according to the invention, e.g. called: solutions, suspensions, emulsions, PIT emulsions, pastes, ointments, gels, creams, lotions, powders, soaps, surfactant-containing cleaning preparations, oils, aerosols and sprays. Other forms of application are e.g. Sticks, shampoos and shower baths. Any customary carriers, auxiliaries and, if appropriate, further active ingredients can be added to the preparation. Preferred auxiliaries come from the group of preservatives, antioxidants, stabilizers, solubilizers, vitamins, colorants, odor improvers.

Ointments, pastes, creams and gels can contain the usual carriers, 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 can contain the usual carriers, e.g. Milk sugar, talc, silica, aluminum hydroxide, calcium silicate and polyamide powder or mixtures of these substances. Sprays can also contain the usual propellants, e.g. Chlorofluorocarbons, propane / butane

, or dimethyl ether. Solutions and emulsions can contain the usual carriers such as solvents, solubilizers and emulsifiers, e.g. water, ethanol, iso- propanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1, 3-butyl glycol, oils, especially 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 contain mixtures of these substances.

Suspensions can 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 can contain the usual carriers such as alkali salts of fatty acids, salts of fatty acid half-esters, fatty acid protein hydrolyzates, isothionates,

Contain lanolin, fatty alcohol, vegetable oils, vegetable extracts, glycerin, sugar or mixtures of these substances.

Surfactant-containing cleansing products may comprise the customary carriers, such as salts of fatty alcohol sulfates, Sulfobemstein- säurehal best, fatty acid protein hydrolysates, isethionates, imidazolinium derivatives, methyl taurates, betaines sarcosinates, Fettsäureamidethersulfate, alkyl, fatty alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable and synthetic oils, lanolin derivatives, ethoxylated Contain glycerin fatty acid esters or mixtures of these substances.

Face and body oils can contain the usual carriers such as synthetic oils such as fatty acid esters, fatty alcohols, silicone oils, natural oils such as vegetable oils and oily plant extracts, paraffin oils, lanolin oils or mixtures of these substances.

Other typical cosmetic application forms are also lipsticks, lip care sticks, mascara, eyeliner, eye shadows, blush, powder, emulsion and wax make-up as well as sun protection, pre-sun and after-sun preparations. The preferred preparation forms according to the invention include, in particular, emulsions.

Emulsions according to the invention are advantageous and contain z. B. said fats, oils, waxes and other fat bodies, as well as water and an emulsifier, as is usually used for such a type of preparation.

The lipid phase can advantageously be selected from the following group of substances:

- mineral oils, mineral waxes

- Oils, such as triglycerides of capric or caprylic acid, as well as natural oils such. B. castor oil; Fats, waxes and other natural and synthetic fat bodies, preferably esters of fatty acids with alcohols of low C number, e.g. with isopropanol, propylene glycol or glycerin, or esters of fatty alcohols with low C number alkanoic acids or with fatty acids;

- Silicone oils such as dimethylpolysiioxane, diethylpolysiloxane, diphenylpolysiloxane and mixed forms thereof.

The oil phase of the emulsions, oleogels or hydrodispersions or lipodispersions for the purposes of the present invention is advantageously selected from the group of esters from saturated and / or unsaturated, branched and / or unbranched alkane carboxylic acids with a chain length of 3 to 30 carbon atoms and saturated and / or unsaturated, branched and / or unbranched alcohols with a chain length of 3 to 30 C atoms, from the group of esters of aromatic carboxylic acid and saturated and / or unsaturated, branched and / or unbranched alcohols with a chain length of 3 to 30 C 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, isononylisononanoate, 2-ethylhexyl palmitate, 2-ethylhexyl allyl ethylate, 2-ethylhexyl lauryl, 2-ethyl hexyl laurate, cyloleate, erucylerucate and synthetic, semi-synthetic and natural mixtures of such esters, e.g. B. Jojoba oil.

Furthermore, the oil phase can advantageously be selected from the group of branched and unbranched hydrocarbons and waxes, the

Silicone oils, the dialkyl ethers, the group of saturated or unsaturated, branched or unbranched alcohols, and also the fatty acid triglycerides, especially the triglycerol esters of saturated and / or unsaturated, branched and / or unbranched alkane carboxylic acids with a chain length of 8 to 24, in particular 12-18 C atoms , The fatty acid triglycerides can for example be advantageously selected from the group of synthetic, semi-synthetic and natural oils, e.g. As 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 can also be used advantageously for the purposes of the present invention. It may also be advantageous to use waxes, for example cetyl palmitate, as the sole lipid component of the oil phase.

The oil phase is advantageously selected from the group consisting of 2-ethylhexyl isostearate, octyldodecanol, isotridecyl isononanoate, isoeicosane, 2-ethyl hexyl cocoate, C ₂ -i ₅ -alkyl benzoate, caprylic capric acid triglyceride, dicapryl ether.

Mixtures of C ₁₂ -i ₅ alkyl benzoate and 2-ethylhexyl isostearate, mixtures of C ₂ -i ₅ alkyl benzoate and isotridecyl isononanoate as well as mixtures of Ci ₂ -i ₅ alkyl benzoate, 2-ethylhexyl isostearate and isotridecyl isononanoate are particularly advantageous.

Of the hydrocarbons, paraffin oil, squalane and squalene can be used advantageously for the purposes of the present invention.

Advantageously, the oil phase can also contain cyclic or linear silicone oils or consist entirely of such oils, although it is preferred, except for the silicone oil or Silicone oils to use an additional content of other oil phase components.

Cyclomethicone (octamethylcyclotetrasiloxane) is advantageously used as the silicone oil to be used according to the invention. However, other silicone oils can also be used advantageously for the purposes of the present invention, for example hexamethylcyclotrisiloxane, polydimethylsiloxane, poly (methylphenylsiloxane).

Mixtures of cyclomethicone and isotridecyl isononanoate, cyclomethicone and 2-ethylhexyl isostearate are also particularly advantageous.

The aqueous phase of the preparations according to the invention advantageously advantageously contains alcohols, diols or polyols of low C number, and also their ethers, preferably ethanol, isopropanol, propylene glycol,

Glycerin, 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 alcohols of low C number, e.g. B. ethanol, isopropanol, 1, 2-propanediol, glycerol and in particular one or more thickeners, which or which can advantageously be selected from the group consisting of silicon dioxide, aluminum silicates, polysaccharides or their derivatives, e.g. Hyaluronic acid, xanthan gum, hydroxypropylmethyl cellulose, particularly advantageously from the group of polyacrylates, preferably a polyacrylate from the group of so-called carbopoles, for example carbopols

Types 980, 981, 1382, 2984, 5984, each individually or in combination.

Mixtures of the abovementioned solvents are used in particular. Water can also be a component of alcoholic solvents.

Emulsions according to the invention are advantageous and contain z. B. said fats, oils, waxes and other fat bodies, as well as water and an emulsifier, as is usually used for such a type of formulation. In a preferred embodiment, the preparations according to the invention contain hydrophilic surfactants.

The hydrophilic surfactants are preferably selected from the group of alkyl glucosides, acyl lactylates, betaines and cocoamphoacetate.

The alkyl glucosides are in turn advantageously selected from the group of alkyl glucosides, which are characterized by the structural formula

distinguish, where R is a branched or unbranched alkyl radical having 4 to 24 carbon atoms and where DP is an average degree of glucosylation of up to 2.

The value DP represents the degree of glucosidation of the alkyl glucosides used according to the invention and is defined as 100 100 100 100

Here, p-ι, p, p ₃ ... and pi represent the proportion of single, double, triple ... i-fold glucosylated products in weight percent. Products with degrees of glucosylation of 1-2 are particularly advantageous according to the invention from 1, 1 to 1, 5, very particularly advantageously selected from 1, 2-1, 4, in particular from 1, 3. The value DP takes account of the fact that alkylglucosides are generally mixtures of mono- and oligoglucosides due to their production. A relatively high content of monoglucosides, typically of the order of 40-70% by weight, is advantageous according to the invention.

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

It is likewise advantageous to employ natural or synthetic raw materials and assistants or 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).

The acyl lactylates are in turn advantageously selected from the group of substances which are characterized by the structural formula II I oo M ^® , where 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 ammonium ions substituted by one or more alkyl and / or by one or more hydroxyalkyl radicals or half the equivalent of an alkaline earth ion.

For example, sodium is advantageous, for example, • Product Pathionic ^® ISL from the American Ingredients Company. The betaines are advantageously selected from the group of substances which are distinguished by the structural formula

distinguish, wherein R ^{2 is} a branched or undisclosed alkyl radical having 1 to 30 carbon atoms.

R ² particularly advantageously denotes a branched or unbranched alkyl radical having 6 to 12 carbon atoms.

Capramidopropylbetaine, for example the product Tego ^® Betaine is advantageous, for example 810 from Th. Goldschmidt AG.

Cocoamphoacetate which is advantageous according to the invention is, for example

Sodium cocoamphoacetate chosen, as it is called Miranol ^® Ultra C32 from the company Miranol Chemical Corp. is available.

The preparations according to the invention are advantageously characterized in that the hydrophilic surfactant or surfactants in concentrations of

0.01-20% by weight, preferably 0.05-10% by weight, particularly preferably 0.1-5% by weight, in each case based on the total weight of the composition, is or are present.

For use, the cosmetic and dermatological preparations according to the invention are applied to the skin and / or the hair in a sufficient amount in the manner customary for cosmetics.

Cosmetic and dermatological preparations according to the invention can be in various forms. So you can z. Legs

Solution, an anhydrous preparation, an emulsion or microemulsion of the type water-in-oil (W / O) or of the type oil-in-water (O / W), a multiple emulsion, for example of the type water-in-oil-in -Water (W / O / W), a gel, a solid stick, an ointment or an aerosol. It is also advantageous to give ectoine in an encapsulated form, e.g. B. in collagen matrices and other common encapsulation materials, e.g. B. as cellulose encapsulations, encapsulated in gelatin, wax matrices or liposomal. In particular, wax matrices as described in DE-OS 43 08 282 have been found to be favorable. Emulsions are preferred. O / W emulsines are particularly preferred. Emulsions, W / O emulsions and O / W emulsions are available in the usual way.

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

According to the invention, O / W emulsifiers are advantageously chosen as co-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 saturated radicals R and R '. 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 can 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) cetyl ether (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 (isolaureth-12), polyethylene glycol (13) cetylstearyl ether (ceteareth-13), polyethylene glycol (14) cetylstearyl ether (ceteareth-14), polyethylene glycol (15) cetyl stearyl ether (ceteareth-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 from 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 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,

Sodium laureth-11 carboxylate can advantageously be used as the ethoxylated alkyl ether carboxylic acid or its salt. Sodium laureth 1-4 sulfate can advantageously be used as the alkyl ether sulfate. Polyethylene glycol (30) cholesteryl ether can advantageously be used as the ethoxylated cholesterol derivative. Polyethylene glycol (25) soyasterol has also proven itself. Polyethylene glycol (60) evening primrose glycerides can advantageously be used as ethoxylated triglycerides (evening primrose = evening primrose).

It is also advantageous to use the polyethylene glycol glycerol fatty acid esters from the group polyethylene glycol (20) glyceryl laurate, polyethylene glycol (21) glyceryl laurate, polyethylene glycol (22) glyceryl laurate, polyethylene glycol (23) glyceryl laurate, polyethylene glycol (6) glyceryl capethylene / cprinate ) Glyceryl oleate, polyethylene glycol (20) glyceryl isostearate, polyethylene glycol (18) glyceryl oleate (cocoat). It is also favorable to select the sorbitan esters from the group polyethylene glycol (20) sorbitan monolaurate, polyethylene glycol (20) sorbitan monostearate, polyethylene glycol (20) sorbitan monoisear To choose polyethylene glycol (20) sorbitan monopalmitate, polyethylene glycol (20) sorbitan monooleate The following can be used as optional W / O emulsifiers which may be advantageous according to the invention:

^* Fatty alcohols with 8 to 30 carbon atoms, monoglycerol esters of saturated and / or unsaturated, branched and / or unbranched alkane carboxylic acids with a chain length of 8 to 24, in particular 12-18 C atoms, diglycerol esters of saturated and / or unsaturated, branched and / or unbranched alkane carboxylic acids with 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 with a chain length of 8 to 24, in particular 12-18 C atoms, diglycerol ethers saturated and / or unsaturated, branched and / or unbranched alcohols with 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 alkane carboxylic acids with a chain length of 8 to 24, in particular 12-18 C atoms and sorbitan esters of saturated and / or unsaturated, branched and / or unbranched alkane carboxylic acids with a chain length of 8 to 24, in particular 12-18, carbon atoms.

Particularly advantageous W / O emulsifiers are glyceryl monostearate, glyceryl, glyceryl monomyristate, glyceryl monostearate, diglyceryl monostearate, Diglycerylmonoisostearat, propylene glycol, propylene glycol monoisostearate, propylene glycol monocaprylate, propylene glycol, sorbitan, sorbitan, sorbitan, Sorbitanmonoisooleat, sucrose, cetyl alcohol, stearyl alcohol, arachidyl, behenyl, Isobehenyl alcohol, selachyl alcohol, chimyl alcohol, polyethylene glycol (2) stearyl ether (Steareth-2), glyceryl monolaurate, glyceryl monocaprinate, glyceryl monocaprylate.

Preparations preferred according to the invention are particularly suitable for protecting human skin against aging processes and against oxidative stress, i.e. against damage by radicals, such as e.g. generated by solar radiation, heat or other influences. It is available in various dosage forms commonly used for this application. It can be used in particular as a lotion or emulsion, such as a 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, as solid pins or as

'' Made up of aerosol. The preparation can contain cosmetic adjuvants which are usually used in this type of preparation, for example Thickeners, plasticizers, wetting agents, surfactants, emulsifiers, preservatives, anti-foaming agents, perfumes, waxes, lanolin, blowing agents, dyes and / or pigments which color the agent itself or the skin, and other ingredients commonly used in cosmetics.

An oil, wax or other fatty substance, a low monoalcohol or a low polyol or mixtures thereof can be used as the dispersing or solubilizing agent. The particularly preferred monoalcohols or polyols include ethanol, i-propanol,

Propylene glycol, glycerin and sorbitol.

A preferred embodiment of the invention is an emulsion which is present as a protective cream or milk and, in addition to the compound or compounds of the formula Ia-m, is, for example, fatty alcohols, fatty acids, fatty acid esters, in particular triglycerides of fatty acids, lanolin, natural and synthetic oils or waxes and Contains 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 oleic alcohol lotions based on a lower alcohol, such as ethanol, or a glycerol, such as propylene glycol, and / or a polyol, such as Glycerin, and oils, waxes and fatty acid esters such as triglycerides from

Fatty acids.

The preparation according to the invention can also be in the form of an alcoholic gel which contains one or more lower alcohols or polyols, such as ethanol, propylene glycol or glycerol, and a thickener, such as

Includes 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 packaged as an aerosol, the usual propellants, such as alkanes, fluoroalkanes and chlorofluoroalkanes, are generally used.

The cosmetic preparation can also be used to protect the hair against photochemical damage, to prevent changes in color shades, discoloration or damage of a mechanical nature. In this case, it is suitably packaged as a shampoo, lotion, gel or emulsion for rinsing, the respective preparation being applied before or after shampooing, before or after dyeing or decoloring or before or after the perm. A preparation can also be selected as a lotion or gel for styling and treatment, as a lotion or gel for brushing or laying a water wave, as a hair lacquer, permanent wave agent, dye or bleaching agent for the hair. In addition to the compound or compounds of the formula Ia-m, the preparation with light protection properties can contain various adjuvants used in this type of agent, such as interfaces, active agents, thickeners, polymers, plasticizers, preservatives, foam stabilizers, electrolytes, organic solvents, silicone derivatives, oils, waxes , Anti-greasy agents, dyes and / or pigments which color the agent itself or the hair or other ingredients commonly used for hair care. The present invention further relates to a process for the preparation of a preparation, which is characterized in that at least one compound of the formula Ia-m with residues as described above is mixed with a cosmetically or dermatologically or for food-compatible carrier, and the use of a compound of the formula la-m for the preparation of a preparation.

The preparations according to the invention can be prepared using techniques which are well known to the person skilled in the art. The mixing can result in dissolving, emulsifying or dispersing the compound of the formula Ia-m in the carrier. In a method preferred according to the invention, the compound of the formula Ia-m is prepared by the cyclization of an appropriately substituted o-hydroxyacetophenone with an anhydride or with an acyl chloride under basic conditions. Then you can

Acyl protective groups are removed. The implementation can be analogous to Kelly, T; Kim M.H .; J. Org. Chem. 1992, 57, 1593-97. Alternatively, the free hydroxy groups are acylated, followed by a Baker-Venkatamaran rearrangement in basic conditions followed by ring closure under acidic conditions. Appropriate

Implementations whose adaptation to the compounds desired here do not pose any problems for the person skilled in the art are known from patent application WO 2002/060889.

Further derivatives of the formula la-m can be obtained by customary reactions on the ring system or derivatization of the functional groups. A person skilled in the art of such syntheses can easily find the reaction conditions necessary for such reactions, such as oxidations, reductions, transesterifications, etherifications, in the generally accessible literature on organic reactions.

It has also been found that compounds of the formula Ia-m can have a stabilizing effect on the preparation. When used in corresponding products, they therefore remain stable for longer and do not change their appearance. In particular, even with prolonged use or longer storage, the effectiveness of the ingredients, e.g. Vitamins. Among other things, this is particularly advantageous in the case of compositions for protecting the skin against the action of UV rays, since these cosmetics are exposed to particularly high levels of exposure to UV radiation.

The positive effects of compounds of the formula Ia-m result in their particular suitability for use in cosmetic or pharmaceutical preparations. The properties of compounds with the formula Ia-m are also to be assessed positively for use in foods or as food supplements or as “functional food”. The further explanations given for foods also apply mutatis mutandis to food supplements and “functional food”.

The foodstuffs which can be enriched with one or more compounds of the formula Ia-m according to the present invention comprise all materials which are suitable for animal or human consumption, for example vitamins and provitamins thereof, fats, minerals or amino acids ". (The foodstuffs can be solid but also liquid, that is to say be present as a drink). Accordingly, the present invention further relates to the use of a compound of the formula la-m as a food additive for human or animal nutrition, and to preparations, the foodstuffs or Dietary supplements and appropriate carriers are included.

Foodstuffs which can be enriched with one or more compounds of the formula la-m according to the present invention are, for example, foods which come from a single natural source, such as 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, according to the present invention, can be enriched with one or more compounds of the formula la-m , are grain of a single plant species and materials made from such plant species, such as Cereal syrup, rye flour, wheat flour or oat bran. Mixtures of such foods are also suitable according to the present

^■ being enriched invention with one or more compounds of formula la-m, for example multivitamin preparations, mineral mixtures or sweetened juice. As further examples of foodstuffs which, according to the present invention, have one or Several compounds of the formula Ia-m can be enriched include food preparations, for example prepared cereals, pastries, mixed drinks, foods specially prepared for children, such as yogurt, diet foods, low-calorie foods or animal feed.

The foods which can be enriched according to the present invention with one or more compounds of the formula Ia-m thus include all edible combinations of carbohydrates, lipids, proteins, inorganic elements, trace elements, vitamins, water or active metabolites of plants and animals.

The foods that can be fortified with one or more compounds of formula la-m according to the present invention are preferably administered orally, e.g. in the form of dishes, pills, tablets, capsules, powders, syrups, solutions or suspensions.

The foods according to the invention enriched with one or more compounds of the formula Ia-m can be prepared using techniques which are well known to the person skilled in the art.

Due to their action, compounds of the formula la-m are also suitable as pharmaceutical ingredients. Compounds of formula la-m can be used, for example, for the preventive treatment of inflammation and allergies to the skin and, in certain cases, for the prevention of certain types of cancer. Compounds of the formula Ia-m are particularly suitable for the production of a medicament for the treatment of inflammation, allergies and irritation, in particular of the skin. Furthermore, drugs can be produced in an effect as a venous tonic, as an inhibitor for cuperose, as an inhibitor of chemical, physical or actinic erythema, as an agent for the treatment of sensitive skin, as a decongestant, as a drainage agent, as

^• Slimming agents, as anti-wrinkle agents, as stimulators for the synthesis of components of the extracellular matrix, as a strengthening agent for improving skin elasticity and as anti-aging agents. In this context, preferred compounds of the Formula la-m anti-allergic and anti-inflammatory and anti-irritant effects. They are therefore suitable for the manufacture of medicines for the treatment of inflammation or allergic reactions.

The invention is explained in more detail below with the aid of examples; the invention can be carried out in the entire claimed range and is not restricted to the examples mentioned here.

Examples Example 1: Preparation of 2-ethoxycarbonyl-7-hydroxyc romon

Sodium (7.6g, 330mmol) is placed under an Ar atmosphere and ethanol (500ml) is slowly added dropwise. The mixture is stirred for about 1 h until the sodium has completely dissolved, then it is cooled to RT with an ice bath. 2 ', 4'-Dihydroxyacetophenone (10g, 66mmol) and diethyl oxalate (36ml, 266mmol) are dissolved in 60mL EtOH (brown orange colored clear solution) added dropwise. The solution is stirred at 70 ° C. for 2 hours. The clear solution is cooled to 0 ° C. with an ice / water bath and brought from pH 13 to pH 4 with about 50 ml of HCl (c = 32%). Then part of the ethanol is removed from the suspension under reduced pressure. The remaining suspension is poured into 300 ml of ice water and extracted with CH ₂ CI ₂ , the aqueous phase is extracted twice with CH ₂ CI ₂ , the org. Phases combined, extracted 3 times with deionized water, once with saturated NaCl solution and the org. Phase dried with Na sulfate, filtered and evaporated to dryness. Yield: 29.1 g of red-brown pulpy solid. The crude yield is concentrated with 100 ml of acetic acid and 1 ml. Sulfuric acid was added and the mixture was stirred under reflux for 2 h and, after cooling, the solid which had precipitated was filtered off with suction, washed neutral with a little CH ₃ COOH and then with deionized water and dried overnight in a vacuum drying cabinet at 40 ° C. and 200 mbar. Yield: 10.1 g = 65.6% of theory. Theory weakly pink powdery ^'solid Recrystallization is carried out in a mixture of toluene and methanol. Yield: 6.6 g = 42.9% of theory. Theory beige colored crystals (HPLC =

100%).

¹ H NMR (300 MHz) in DMSO δ (ppm): 1.35 (t, 3H), 4.37 (q, 2H), 6.84 (s,

1 H), 6.9 (d, 1 H), 6.96 (dd, 1 H), 7.9 (d, 1H), 11.0 (bs, 10H). MS (m / z): 234 (M ⁺ )

Example 2: Preparation of 7-hydroxy-4-oxo-4H-chromon-2-carboxylic acid

2-ethoxycarbonyl-7-hydroxychromone (14.5 g, 62 mmoles) is initially dissolved in ethanol (400 ml) at 50 ° C. and sodium carbonate (20 g, 190 mmoles) dissolved in H ₂ O-VE (200 ml) are added dropwise. The mixture is stirred under reflux at 80 ° C. for 3 hours. After cooling, acidify with 2N HCI. The precipitated white solid is filtered off, washed neutral and dried. Yield K1: 6.5 g = 50.9% of theory of almost white powder ¹ H NMR (300 MHz) in DMSO δ (ppm): 6.8 (s, 1 H), 6.9 (d, 1 H), 6.95 (dd, 1 H), 7.9 (d, 1 H), 11.0 (bs, 10H), 14.5 (bs, 1COOH) MS (m / z): 206 (M ⁺ )

Example 2a: Preparation of 7-hydroxy-4-oxo-4H-chromon-2-carboxylic acid (1-ethyl-hexyl) ester

The ester is obtained by transesterification of the acid from Example 2 with 1-ethylhexyl alcohol.

¹ H NMR (300 MHz) in CDCI ₃ δ (ppm): 0.79-0.88 (m, 6H), 1.18-1.37 (m, 8H), 1.65 (ddd, 1H), 7.02-7.06 (m, 1H + 2H.arom .), 8.02 (d, 1H aroma.)

Example 3: Preparation of 5,7-dihydroxy-4-oxo-4H-chromene-2-carboxylic acid Step 1 :

2,4,6-trihydroxyacetophenone is initially dissolved in pyridine under an argon atmosphere and a little 4- (dimethylamino) pyridine (catalytic amount) is introduced. Now the ethyl chloroformyl formate is slowly added dropwise. After everything has been metered in, the apparatus is heated to 80 ° C. with an oil bath and stirred at this temperature for 2 hours. The apparatus is allowed to cool to room temperature, the dark brown suspension is added to about 200 ml of ice water and 200 ml of CH ₂ Cl _{2 are} added and the mixture is extracted. The aq. Phase shaken again twice with 50mL CH ₂ CI ₂ and the org. black-colored phases combined, washed twice with 50 ml of demineralized water, 3 times with 2 molar HCl (pyridine-free) and once with saturated NaCl solution. There remains a clear black-brown org. Phase, which is dried with Na ₂ S0 ₄ . The organic phase is over a glass frit with a bit in CH ₂ CI ₂ / EEE: given angeschlämmten silica gel # 7734, it is with about 250 ml CH ₂ CI ₂ / EEE (5: 1) (5 1) and washed the solution concentrated by rotary evaporation. Yield 8.5 g of yellow solid. This solid is used for the next stage.

Step 2:

Oxalicacid-2-ethoxycarbonyl-7-ethoxyoxalyloxy-4-oxo-4H-chromen-5-ylesterethyl ester from step 1 is initially dissolved in ethanol at room temperature, Na ₂ CO ₃ dissolved in H ₂ O-VE is added dropwise. The mixture is then heated to 70 ° C. and stirred for 4 hours at this temperature. After cooling, the reaction mixture is mixed with 100 ml of ethyl acetate and made weakly acidic with 1 N HCl. The aqueous phase is separated off and extracted again. The org. Phases are combined, 3x with H ₂ 0-VE, 1x with sat. NaCl solution. washed, dried with Na ₂ S0, filtered and evaporated. After recrystallization, 0.4 g of yellow fine crystals (HPLC = 98.4%) are obtained.

¹ H NMR (300 MHz) in DMSO δ (ppm): 6.2 (d, 1 H), 6.4 (d, 1 H), 6.8 (s, 1 H), 11.1 (bs, 10H), 12.5 (bs, 10H) MS (m / z): 222 (M ⁺ )

Example 4: Preparation of 5,7-dihydroxy-4-oxo-4H-chromene-2-carboxylic acid - (1-ethyl-hexyl) ester

The ester is obtained by transesterification of the acid from Example 3 with 1-ethylhexyl alcohol.

Example 5: Preparation of 5,7-diacetoxy-3-acetyl-2-methyl-chromen-4-one

2,4,6-trihydroxyacetophenone is initially dissolved in acetic anhydride and sodium acetate is added. The suspension is allowed to stir under reflux for 10 h. The reaction mixture is then poured into about 300 ml of ice water and extracted twice with ethyl acetate (EEE), the org. Phases are combined, washed ₃ times with H ₂ O-VE. The remaining solution is further with Na ₂ HC0 ₃ solution. washed. The organic phase is dried over Na ₂ S0, filtered and evaporated. ¹ H NMR (300 MHz) in DMSO δ (ppm): 7.1 (d, 1H), 7.4 (d, 1H) MS (m / z): 318 (M ⁺ )

Example 6: Preparation of 3-acetyl-5,7-dihydroxy-2-methyl-4H-1-benzopyran-4-one

2.5 g of 2,4,6-trihydroxyacetophenone were placed under argon at room temperature in solution in 50 ml of tetrahydrofuran, yellow solution, heated to 50 ° C., 7.5 g of potassium carbonate were added and the mixture was stirred at this temperature for 1 hour. Now 2 ml of acetyl chloride were slowly added dropwise at 50 ° C., during which the suspension turned light yellow after everything was added dropwise, the mixture was heated to reflux and allowed to reflux for 4 hours. During the 4 hours the suspension changed color from yellow to orange. The heating bath and stirrer were turned off and the orange

Chilled suspension.

H ₂ O-VE was added with stirring and then carefully acidified with 25% HCl (little or no foaming!). Now the clear yellowish solution was poured into a separatory funnel and extracted with EEE, the aq. Phase extracted 1x with EEE, the org. Phases combined, 2x with H2O-VE, 1x with sat. NaCl. Washed solution, dried with Na ₂ S0 ₄ , filtered and evaporated.

Yield: 3g light orange solid = 95% of theory NMR (300MHz) in DMSO δ (ppm): 2.4 (s, 3H), 2.5 (s, 3H), 6.25 (d, 1H), 6.37 (d, 1H), 12.5 (s, 10H), 12.8 (s , OH) MS (m / z): 234 (M ⁺ )

Example 7: Preparation of 5,7-dihydroxy-2-ethylpentylchromen-4-one

I. Step:

2,4,6-trihydroxyacetophenone (5g-26.3mmol) is added to 90ml toluene, 14g potassium carbonate is dissolved in 70ml demineralized water and 1g tetra-n-butylammonium hydrogen sulfate is added to the solution. 2-Ethylhexanoic acid chloride (20.5 ml-119.7 mmol) is added dropwise to the two-phase mixture over the course of 10 minutes with vigorous stirring. The two-phase mixture is then heated with stirring at 70 ° C. for 5 hours. The upper dark red organic phase is then separated off, the aqueous phase is shaken twice with dichloromethane, the organic phases are combined, washed with saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated to dryness on a Rotavapor (bath temperature: 50 ° C.).

M (R): 19.3g

2nd stage: 19.3g of the 1st stage are dissolved in 600ml THF and lithium hydroxide (4.4g-

183.7 mmol) added. The mixture was then added

Reflux cooked for 5.5h. The red-brown reaction solution is approx.

800g ice cream + 100ml conc. Poured HCI, extracted several times with dichloromethane, the orange-colored combined organic phases washed with saturated sodium chloride solution, dried over sodium sulfate, filtered and evaporated to dryness on a rotary evaporator (bath temperature: 50 ° C.).

M (R): 17.2g

3rd stage:

17.2g of the 2nd stage are dissolved in 200ml acetic acid and 2ml conc. Sulfuric acid added. The mixture is then stirred under reflux for 7 hours. The red-brown cloudy solution is poured onto about 500 g of ice, the red-brown precipitated solid is suction filtered, taken up with dichloromethane and extracted several times with dichloromethane together with the aqueous filtrate, the combined organic phases are washed with saturated sodium chloride solution, dried over sodium sulfate, filtered and evaporated to dryness on a rotary evaporator (bath temperature: 50 ° C). m (R): 18.4g residue, TLC: one spot The residue is dissolved in a little methanol and deionized water is added, a beige solid precipitating out, which is suctioned off through a small suction filter. m (K): 1, 65g beige solid,

The filtrate is concentrated again and the distillation residue with

100 ml of heptane are added, a solid precipitates, which is suctioned off through a suction filter. m (K2): 2.27 g light brown solid m (K total): 3.92 g are 52.3% of the theoretical yield based on the

Use on 2,4,6-trihydroxyacetophenone.

¹ H NMR (300 MHz) in DMSO δ (ppm): 0.9 (m, 6H), 1.15-1.3 (m, 4H), 1.55-

1.65 (m, 4H), 2.45 (q, 1 H), 6.17 (s, 1 H), 6.2 (d, 1 H), 6.35 (d, 1 H), 10.75

(bs, OH), 12.85 (s, OH)

MS (m / z): 276 (M ⁺ )

Example 8: Process for 5,7-dihydroxy-3- (2-methoxy-acetyI) -2-methoxymethyl-chromen-4-one

Step 1 :

10g 2,4,6-trihydroxyacetophenone (52.6mmol) is introduced into the apparatus under an argon atmosphere, dissolved in 500ml dichloromethane (light yellow solution) and 50ml pyridine added. Then 30 ml of methoxyacetyl chloride (327.6 mmol) are slowly added dropwise, the temperature rising from 23 ° C. to 30 ° C. The light yellow solution is then stirred under reflux for 4 h. TLC (CH ₂ CI ₂ / MeOH: 9/1): no AM, 1 spot in front and one behind AM spot The solution is poured onto about 500 g of ice and about 20 ml of HCl-w = 32% (pH = 3) and then extracted several times with dichloromethane. The yellow organic phase is washed once with saturated NaCl solution, dried over sodium sulfate, filtered and evaporated to dryness on a rotary evaporator (bath temperature: 50 ° C.). m (R): 27.08g orange oily residue

The residue is dissolved in dichloromethane / methanol (9/1) and filtered through a 10 cm high layer of silica gel (# 7734) for minimal purification and the filtrate is concentrated on a rotary evaporator. m (R2): 25g yellow oily residue

Step 2:

R2 is dissolved in 100ml pyridine, heated to 50 ° C, then with 8g

Potassium hydroxide (142.5mmol) was added and the orange suspension was further heated at 50 ° C. for 1.5 hours.

The orange-brown sticky mixture is then adjusted to pH = 3 with acetic acid solution, extracted several times with ethyl acetate, the orange-colored organic phase is washed with saturated sodium chloride solution, dried over sodium sulfate, filtered and evaporated to dryness on a rotary evaporator (bath temperature: 50 ° C.).

m (R): 19g orange oily residue

Step 3:

R is dissolved in 100 ml of glacial acetic acid and 3.6 ml of concentrated sulfuric acid are added. The mixture is then boiled under reflux for 2 hours. The cooled reddish suspension is poured onto approx. 300 g of ice, resulting in a red-brown cloudy solution.

It is extracted several times with ethyl acetate, the red organic phase is washed with saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated to dryness on a rotary evaporator (bath temperature: 50 ° C.).

m (R): 9.4 g red-brown oily residue

Since the residue still smells of acetic acid, is in dichloromethane and

Dissolved ethyl acetate and neutralized with an aqueous sodium hydrogen carbonate solution, resulting in an ocher-colored solid, which was suction filtered and dried in a vacuum drying cabinet at 45 ° C. m (K): 1.6 g of light brown solid are based on the use of 2,4,6-trihydroxyacetophenone 10.1% of theory. Theory related.

¹ H NMR (300 MHz) in DMSO δ (ppm): 3.3 (s, 3H), 3.32 (s, 3H), 4.37 (s,

2H), 4.45 (s, 2H), 6.24 (d, 1 H), 6.37 (d, 1 H), 12.23 (bs, 10H), 12.67 (s,

10H).

MS (m / z): 294 (M ⁺ )

Example 9: Preparation of 7-isopropyl-4-oxo-4H-chromon-3-carbaldehyde

7-Hydroxy-4-oxo-4H-chromon-3-carbaldehyde (2g, 10.5mmol) is dissolved under N ₂ atmosphere in N, N-dimethylformamide (25ml), potassium carbonate (1, 8g, 13mmol) and potassium iodide (50mg ) added and stirred at RT for 1 h. Then 2-bromopropane (2ml, 21mmol) is slowly added dropwise and Heated to 55 ° C for 2 hours. Another 2 ml of 2-bromopropane are added and the mixture is stirred at 55 ° C. for a further 2.5 h. After stirring at RT for 12 h, the reaction mixture is poured into 60 ml of demineralized water, acidified with dilute HCl and extracted with 150 ml of EEE. The aqueous phase is then extracted twice with EEE. The united org. Phases twice with 150 ml of demineralized water and once with saturated NaCl solution, dried with Na sulfate, filtered and the solvent removed. For the purification, the crude product is dissolved in 10 ml of eluent (CH ₂ Cl ₂ / MeOH 9.5 / 0.5) and filtered through 250 g of silica gel # 109385. Yield: 281 mg = 11.52% of theory. (HPLC content: 89.3%). ¹ H NMR (300 MHz) in DMSO δ (ppm): 1.3 (d, 6H), 4.9 (m, 1 H), 7.1 (dd, 1 H), 7.3 (d, 1 H), 8.85 (s, 1 H) ), 10.1 (s, 1H).

Example 10: Preparation of L-ascorbyl-6 [5,7-dihydroxy-4-oxo-4H-chromone-2-carboxylate]

5,7-Dihydroxy-4-oxo-4H-chromon-2-carboxylic acid (400mg, 1.8mmol) dissolved in sulfuric acid 95-97% (10ml) is placed under an argon atmosphere and heated to 55 ° C. Ten 100 mg portions of L (+) - ascorbic acid are slowly added, keeping the temperature at a maximum of 75 ° C. The mixture is then stirred at this temperature for 12 h. The reaction mixture is cooled with an ice bath and placed in 50 ml of ice water, mixed with EEE, filtered through Celite, the aqueous. Phase separated, again extracted with a little EEE, the org. Phases combined, 4x with approx. 20ml H ₂ 0-VE, 1x with sat. NaCl solution. washed neutral, dried with Na ₂ S0 ₄ , filtered and evaporated.

Yield: 250mg

HPLC-ESI-MS shows [M + H] ⁺ = 365.1

Example 11: Preparations

The following are examples of formulations for cosmetic preparations which contain compounds according to Examples 1-3. For the rest, the INCI names of the commercially available 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

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

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

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

Table 1 (continued)

Table 1 (continued)

Table 2: O / W emulsions, numbers in% by weight

Table 2 (continued)

Table 2 (continued)

Table 3: Gels, numbers in% by weight

Claims

claims

1. Compound selected from the compounds of the formulas la-lc

where R ¹ and R ^{2 can be the} same or different and are selected from H, -C (= 0) -R ⁷ , -C (= 0) -OR ⁷ , straight-chain or branched C to C ₂ o-alkyl groups, - straight-chain or branched C ₃ - to C ₂₀ -alkenyl groups, straight-chain or branched d- to C ₂₀ -hydroxyalkyl groups, where the hydroxyl group can be bound to a primary or secondary carbon atom of the chain and the alkyl chain can also be interrupted by oxygen, and / or - C ₃ - to C-io-cycloalkyl groups and / or C ₃ - to Cι ₂ - cycloalkenyl groups, where the rings can also be bridged by - (CH ₂ ) _n - groups with n = 1 to 3, R ³ represents H or straight-chain or branched C to C ₂₀ alkyl groups, R ⁴ represents H or OR ⁸ , R ⁵ and R ^{6 may be the} same or different and are selected from --H, -OH, straight-chain or branched Cr to C ₂ o-alkyl groups, - straight-chain or branched C ₃ - to C ₂ o-alkenyl groups, - straight-chain or branched Cr to C ₂ o-hydroxyalkyl groups, where the hydroxy group can be bound to a primary or secondary carbon atom of the chain and further the alky Oil chain can also be interrupted by oxygen and R ⁷ stands for H, straight-chain or branched C to C ₂₀ alkyl groups, a polyhydroxy compound, such as preferably an ascorbic acid residue or glycosidic residues, and R ⁸ stands for H or straight-chain or branched Cr to C ₂₀ - Alkyl groups, where one of the radicals R ¹ or R ^{2 is} H or a straight-chain or branched Cι_ ₂ o-alkyl group and the other radical is - C (= 0) -R ⁷ , -C (= 0) -OR ⁷ or a straight-chain or branched Cr to C ₂ o -alkyl group, and at least one of the radicals R ³ or R ^{4 is} not H when R ⁷ is H.

2. Compound according to claim 1, characterized in that the compound according to formula Ia is a compound selected from the compounds having the formulas Id-Im:

3. A compound according to claim 1, characterized in that at least 2 of the substituents R ¹ , R ² , R ⁴ -R ^{6 are} different from H.

4. A compound according to claim 1, characterized in that a substituent from R ¹ and R ^{2 is} -C (= 0) -R ⁷ or -C (= 0) -OR ⁷ .

5. A compound according to at least one of the preceding claims, characterized in that R ³ is H and R ⁴ is OH, preferably at least one of the radicals R ⁵ and R ^{6 being} OH.

6. A compound according to at least one of claims 1 to 4, characterized in that R ⁵ and R ^{6 are} H.

7. Use of at least one compound of the formula Ia to Im or a preparation comprising at least one compound of the formula Ia to Im with residues according to at least one of Claims 1 to 6 for the care, preservation or improvement of the general condition of the skin or hair.

8. Use of at least one compound of the formula Ia to Im or a preparation comprising at least one compound of the formula Ia to Im with residues according to at least one of claims 1 to 6 for prophylaxis against time and / or light-induced aging processes of human skin or human hair, in particular for prophylaxis against dry skin, wrinkling and / or pigment disorders, and / or for reducing or preventing damaging effects of UV rays on the skin.

9. Use of at least one compound of the formula Ia to Im or a preparation comprising at least one compound of the formula Ia to Im with residues according to at least one of claims 1 to 6 for the prophylaxis against or reduction of skin imperfections, such as wrinkles, fine lines, rough skin or large-pored skin.

10. Use of at least one compound of the formula Ia to Im with residues according to at least one of claims 1 to 6 for the preparation of a preparation suitable for the prophylaxis and / or prevention of premature skin aging, in particular for the prophylaxis and / or prevention of wrinkles due to light or aging Skin, to reduce pigmentation and keratosis actinica and for the prophylaxis and / or treatment of all diseases that are associated with normal aging or light-related aging of the skin.

11. Use of at least one compound of the formula Ia to Im with residues according to at least one of claims 1 to 6 for the manufacture of a preparation suitable for the prophylaxis and / or treatment of skin diseases which are associated with a keratinization disorder which relates to differentiation and cell proliferation, especially for the treatment of acne vulgaris, acne comedonicä, polymorphic acne, acne rosaceae, nodular acne, acne conglobata, age-related acne, the side effects of acne, such as acne solaris, medication-related acne or professional acne, for the treatment of other disorders of keratinization, especially ichthyosis, ichtyosi-like conditions, Darrier's disease, keratosis palmoplantaris, leukopiasias, leukoplasiform conditions, skin and mucous membrane lichen (buccal) (lying), for the treatment of other skin diseases that are associated with a keratinization disorder and have an inflammatory and / or immunoallergic component, and in particular all forms of psoriasis affecting the skin, the mucous membranes and the fingers and toenails, and psoriatic rheumatism and skin atopies such as eczema or respiratory atopy or also the gum hypertrophy.

12. Use of at least one compound of the formula Ia to Im with residues according to at least one of claims 1 to 6 for the preparation of a preparation suitable for the prophylaxis and / or treatment of all benign or malignant growths of the dermis or epidermis, which may be of viral origin, such as Verruca vulgaris. Veruca plana, Epidermodysplasia verrueiformis, oral papillomatosis, Papillo-matosis florida, and the growths that can be caused by UV radiation, in particular the epithelioma basocellular and epithelioma spinocellulare.

13. Preparation containing at least one compound of the formula Ia to Im with residues according to at least one of claims 1 to 6, and at least one further skin-care ingredient and at least one carrier suitable for topical applications.

14. Preparation according to claim 13, characterized in that the preparations one or more compounds of formula la to Im in an amount of 0.01 to 20 wt .-%, preferably in an amount of 0.1 to 10 wt .-% contains.

15. Preparation according to at least one of the preceding claims, characterized in that it is at least one further skin-care ingredient to one or more antioxidants and / or vitamins, preferably selected from vitamin C and its derivatives, DL-α-tocopherol, tocopherol-E - Acetate, nicotinic acid, pantothenic acid and biotin, where the preparation preferably contains no retinol derivative.

16. Preparation according to at least one of the preceding claims, wherein the preparation contains one or more UV filters, which are preferably selected from the group consisting of 3- (4 ^' - methylbenzylidene) -dl-camphor, 1- (4-tert- Butylphenyl) -3- (4-methoxyphenyl) propane-1, 3-dione, 4-isopropyldibenzoylmethane, 2-hydroxy-4-methoxybenzophenone, octyl methoxycinnamate, 3,3,5-trimethylcyclohexylsalicylate, 4- (dimethylamino) benzoic acid2 -ethylhexyl ester, 2-cyano-3,3-diphenylacrylic acid-2-ethylhexyl ester, 2-phenylbenzimidazole-5-sulfonic acid and their potassium, sodium and triethanolamine salts.

17. Preparation according to at least one of the preceding claims, characterized in that at least one further skin-care ingredient is pyrimidinecarboxylic acids and / or aryloximes, preferably ectoine.

18. A process for the preparation of a preparation, characterized in that a compound of the formula Ia to Im is mixed with residues according to at least one of claims 1 to 6 with a cosmetically or dermatologically or food-compatible carrier.

19. A process for the preparation of a compound of formula Ia to Im with radicals according to at least one of claims 1 to 6, characterized in that the preparation is carried out by the cyclization of an appropriately substituted o-hydroxyacetophenone with a suitable anhydride or with a suitable acyl chloride.