EP2238121A1

EP2238121A1 - Uva filter based on ascorbic acid derivatives

Info

Publication number: EP2238121A1
Application number: EP09707578A
Authority: EP
Inventors: Thomas Rudolph; Philipp Buehle
Original assignee: Merck Patent GmbH
Current assignee: Merck Patent GmbH
Priority date: 2008-02-06
Filing date: 2009-01-14
Publication date: 2010-10-13
Also published as: CN101939309A; US20100322880A1; WO2009097951A1

Abstract

The invention relates to compounds of formula (I) wherein R1, R2, R3, R4 have the meaning cited in the claims, to methods for the production thereof, to agents containing said compounds and to their use for the functionalisation of matrices, in particular their use as skin and/or hair-binding UV filters.

Description

UVA filters based on ascorbic acid derivatives

The invention relates to the use of at least one UVA filter on the basis of ascorbic acid derivatives, as well as specific ascorbic acid derivatives and a process for their preparation.

The functionalization according to the invention of proteinaceous matrices, in particular the skin, the hair and / or the nails, is effected by covalent anchoring or strong electrostatic interaction. This leads to an immobilization of the desired active ingredients, for example U VA filters.

A preferred field of application of the use according to the invention is the UVA protection. The human skin is subject to certain

Aging processes that are partly due to intrinsic processes (chronoaging) and partly due to exogenous factors (environmental, e.g., photoaging).

The exogenous factors include, in particular, sunlight or artificial radiation sources with a comparable spectrum and compounds which can be formed by the radiation, such as undefined reactive photoproducts, which can also be free-radical or ionic.

There are a variety of organic and inorganic UVA filters and

Antioxidants are known that can absorb UVA radiation and trap free radicals. They are thus able to protect human skin. These compounds catalyze the transformation from UV light to heat.

Due to lack of skin adhesion but the protection period is limited, especially because conventional UVA filters can be washed off very easily, for example, sweat or water. It is known, for example, from WO 2006/018104 to derivatize UVA filters in such a way that they can bind covalently to the stratum corneum of the epidermis via a reactive molecular part and thus functionalize the skin with the UVA filter. For the effective attachment to proteins and

Amino acids of the outer skin layers, it is necessary that the corresponding UVA filter derivatives have the highest possible reactivity of their bondable molecular parts.

There is therefore an increasing need for skin-friendly compounds which are able to functionalize protein-containing matrices and can be incorporated in a suitable manner into cosmetic or pharmacological preparations.

It has now surprisingly been found that ascorbic acid derivatives, in particular of ascorbic acid derivatives substituted in the 6- and / or 5-position by active substance radicals, are outstandingly suitable for the functionalization of matrices. In addition, it has now surprisingly been found that their stability can be significantly increased by hydrophobizing the derivatives. Improved stability in the sense of this invention means an improved stability of the derivatives to oxidation and / or to hydrolysis and / or to heat and / or to electromagnetic radiation (for example UVA light).

This effect is particularly noticeable when in the B-part of the molecule, as described below, the two alkyl moieties A ¹ in NA ' ₂ of R ¹⁰ or the alkyl moiety A' in OA ¹ of R ^{10 are} each at least 5 non-aromatic C atoms exist. Such a hydrophobization of the molecule also makes it possible to increase the use concentration in the end product and, coupled therewith, to considerably increase the activity. Preferred matrices here are skin, hair and / or nails, whereby the general principle can also be applied to the functionalization of synthetic polymer matrices containing amino groups or thiol groups, isolated proteins or gelatin. The products formed by binding to such matrices may also themselves be used as cosmetic agents for the preparation of cosmetic products. It can be derivatized according to the invention both D- and L-ascorbic acid or mixtures thereof.

A first subject of the invention is therefore the use of at least one UVA filter based on ascorbic acid derivatives.

Of ascorbic acid (vitamin C), often used as a natural antioxidant in cosmetics or food indus- try, it is known that, depending on various parameters such as oxygen, pH,

Metal ion concentration (for example of iron or copper) or

Temperature significant losses due to vitamin C degradation occur. [H.-D.

Belitz, W. Grosch, Textbook of Food Chemistry, Springer-Verlag, 1987, 3rd edition, p. 337.]

In EP 0664290 derivatives of ascorbic acid are described, wherein the 2-position or also the 2- and 6-position is esterified by cinnamic acid. These ascorbic acid derivatives are used as antioxidants or according to EP 104631 as NO donors.

EP 0917871 describes ascorbic acid derivatives whose hydroxy group in the 4-position by CrC ₆ alkoxycarbonyl and their hydroxy groups in the 5- and / or 6-position by CrC ₂ o-acyl or CrCe-alkoxycarbonyl are substituted, wherein the acyl chains branched, unbranched, saturated or (multiple) are unsaturated, ie based on fatty acids. - A -

Aromatic systems are excluded. These compounds are also used as antioxidants.

EP 1527777 describes ascorbic acid derivatives in which at least one hydroxy group of ascorbic acid is esterified with a benzoic acid, preferably a gallic acid. The compounds are used inter alia as inhibitors of a tyrosinase activity or as

Hemmer described for melanin synthesis. The inventive

Use for the functionalization of matrices is not mentioned or even suggested.

In G. Tschank et al, Biochem. J., 1994, 300, 75-79 the compounds O ⁶ - (2-acetoxybenzoyl) -L-ascorbate and O ⁵ O ⁶ -bis (2-acetoxybenzoyl) -L-ascorbate are described. These compounds are capable of supporting the activity of the enzyme prolyl 4-hydroxylase, but the bis-substituted compound has a lower affinity for the enzyme.

For the use according to the invention, in particular at least one ascorbic acid derivative of the formula I is suitable,

in which

R ¹ or R ^{2 are} each independently of the other hydroxy, -O-alkyl, -OC (O) -alkyl, -OPO ₃ M or O-glycosyl, alkyl C 1 -C ₂₀ -alkyl, M alkali or alkaline earth metal cation or H,

R ³ or R ^{4 are} each independently hydroxy or a radical B and B is the radical of a UVA filter with the proviso that at least one of the radicals R ³ or R ^{4 is} a radical B and that R ¹⁰ in the below-mentioned formula II of the radical B for CiC _Σ o-alkyl, NA ' ₂ or OA ', wherein A ^{1 is} branched or linear C ₅ -C ₂ 0 alkyl.

dC ₂ o-alkyl is an alkyl group having 1 to 20 carbon atoms, for example methyl, ethyl, propyl, n-butyl, tert-butyl, n-pentyl, n-hexyl, 2-ethyl-hexyl, n-dodecyl or lauryl.

C ₅ -C ₂ o-alkyl based on the radical B for A ¹ in NA _'2 or OA ¹ is an alkyl group having 5 to 20 carbon atoms, for example n-pentyl, n-hexyl, n-octyl, 2-ethyl -hexyl, tert-butylmethyl, 2,5-dimethylhexyl, 1,3,5-trimethylheptyl,, n-dodecyl, 8-ethyldodecyl, 6-propylundecyl, 5-ethyl-3-methyldecyl, 4-hexyldecyl, 2 Pentylnonyl or n-lauryl.

Suitable alkoxy radicals for R ¹ or R ² are those whose alkyl group contains 1 to 20 C atoms, preferably 1 to 6 C atoms, particularly preferably 1 to 4 C atoms. Examples of alkoxy groups are methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy or tert-butoxy.

The group -OPO ₃ M is preferably the -OPO ₃ H group, but it is also possible to use salts of the formula I where M in formula I is an alkali metal cation, for example Na or K, or an alkaline earth metal cation, for example of Mg or Ca, corresponds.

The attachment of a carbohydrate in position 2 or 3 of ascorbic acid, referred to as O-glycosyl in formula I, can be used, for example, for monosaccharides such as ribose, arabinose xylose, lyxose, allose, altrose, glucose, mannose, gulose, idose, galactose, talose, ribulose , Xylulose, psicose, fructose, sorbose or tagatose. In this list, both isomers, ie in each case the D or L forms are included. Preferably, glucose, galactose or fructose, most preferably glucose, are used.

In principle, however, also suitable are disaccharides, such as sucrose (or else called sucrose), lactose, trehalose, maltose, cellobiose,

Gentiobiose or melibiose. This list includes both the α and β forms.

From the group of disaccharides are preferably sucrose or lactose, particularly preferably sucrose used.

Preferably, the radical R ¹ in formula I is hydroxyl and R ² is -O-alkyl, -OC (O) -alkyl, -OPO ₃ M or O-glycosyl, as described above, wherein alkyl is preferably alkyl having 1 to 6 C Atoms means.

Preferably, the radical R ² in formula I is hydroxy and R ¹ is -O-alkyl, -OC (O) -alkyl, -OPO ₃ M or O-glycosyl, as described above, wherein alkyl is preferably alkyl having 1 to 6 C Atoms means.

Particularly preferably, both radicals R ² and R ^{1 are} hydroxy.

In a preferred embodiment, the radical R ^{3 is} hydroxy and R ⁴ is a radical B, as described above and in the following.

However, according to the invention it is also possible to use mixtures of ascorbic acid derivatives of the formula I in which the radical B is both R ³ and R ⁴ , and also R ³ or R ⁴ .

The radical B is as described above and below, linked via an ester function to the position 5 and / or 6 of the formula I. Particularly preferably, the radical B is bonded via a carbonyloxy function. The radicals R ¹ and R ^{2 of} the ascorbic acid derivatives of the formula I are chosen so that when applied to the matrix, in particular the skin, the hair and / or the nails, or even when applied to isolated proteins or gelatin, bonds to reactive groups of Matrix, such as amino and / or thiol groups. The binding reaction is facilitated if, by oxidation of the hydroxyl groups R ¹ and / or R ^2, activation of the ascorbic acid derivative of the formula I occurs by degradation. The hydroxyl groups R ¹ and / or R ² can also be formed by hydrolysis from an ascorbic acid derivative of the formula I where R ¹ and / or R ² ≠ H when applied to the matrix.

The theory of the further functionalization of the matrix is described below via a binding activation by an ascorbic acid degradation, but the functionalization of the matrices should not be bound to this theory.

In Scheme 1, the ascorbic acid derivative decomposes into xylosone and / or 4-deoxypentosone, where in the formulas of Scheme 1, R ^{3 is} OH or a radical B and R ^{4 is} a radical B, as previously described:

Scheme 1:

R ³ R3

Xyloson

The reactive dicarbonyl compounds xylosone and 4-deoxypentosone are able to react with proteins and amino acids in the manner of a Maillard reaction. This step corresponds to an integration of the active ingredient-carrying radicals R ³ and / or R ⁴ into the matrix. The matrix is therefore functionalized according to the active ingredient residue.

Compared to, for example, non-binding UV filters, this mechanism has two additional advantages, namely the antioxidant (degradation) reaction of the ascorbic acid base body and, if appropriate, a browning reaction analogous to the Maillard reaction (self-tanning component).

In a variant of the invention it is particularly preferred if the radical B in formula I is a substituent which absorbs UVA radiation, for example a cosmetic UVA filter, preferably of the formula II,

in which

R ⁵ to R ⁹ and R ¹¹ to R ^{12 are} each independently H, -OH ₁ -OA, -A, -NH ₂ , -NHA, -NA ₂ , -NH- (CH ₂ -CH ₂ -OVH, -N [(CH ₂ -CH ₂ -O) _n -H] ₂ , - [NHA ₂ ] X, -

[NA ₃ ] X, -SO ₃ H, - [SO ₃ ] X or 2H-benzotriazol-2-yl and

A is alkyl having 1 to 20 C atoms, n is an integer from 1 to 25,

X is the counterion to the cations [NHA ₂ ] ⁺ and [NA ₃ ] ⁺ or the anion [SO ₃ ] ^" and

Y and Z are each independently -ascorbyl, hydroxy, -O-2-ethylhexyl, -O-hexyl, -OA or -NH-C (CH ₃ ) ₃ and

R ^{10 is} A, NA ' ₂ or OA ¹ , where A ^{1 is} branched or linear C ₅ -C ₂₀ -alkyl, more preferably having at least five contiguous carbon atoms. By selecting suitable substituents A or A ¹ of substituent R ^{10 of} the radical B, the hydrophobicity of the total molecule can be controlled.

However, it is also possible for partial charges to be balanced in the molecule itself, i. that compounds of the formula I can exist as a zwitterionic structure.

Depending on the pH, these compounds may carry partial charges, as follows for the compound 2- (4-dihexylamino-2-hydroxy-benzoyl) benzoic acid (R) -2 - ((R) -3,4-dihydroxy-) 5-oxo-2,5-dihydro-furan-2-yl) -2-hydroxyethyl ester is shown: as ammonium compound,

as a zwitterionic compound or

as ascorbate.

Compounds of the formula I can also be used as salts according to the invention, ie at least one hydroxyl group of the Ascorbic acid backbone is deprotonated and the charge is balanced by a counter cation, for example an alkali or alkaline earth metal cation.

Further preferred combinations are disclosed in the claims.

Particularly preferred embodiments of compounds of the formula I can be seen in the partial structure II for the radical B, as described above. Preferably, R ^{10 of} the radical B is NA ' ₂ or OA ¹ , particularly preferably NA' ₂ , where A ^{1 is} branched or linear C ₅ -C ₂₀ -alkyl.

The preparation in general of the compounds of the formula I ₁ as described above can be carried out by methods known to the person skilled in the art from methods known per se. The reaction conditions for esterifications are well known in the art, and selecting the appropriate reaction conditions is one of the standard skill of the art.

Another object of the invention are compounds of the formula I.

in which

R ³ or R ^{4 are} each independently hydroxy or a radical B and B is a radical of the formula II,

in which

R ⁵ to R ⁹ and R ¹¹ to R ^{12 are} each independently H, -OH, -OA, -A, -NH ₂ , -NHA, -NA ₂ , -NH- (CH ₂ -CH ₂ -O) _n - H, -NJ (CH ₂ -CH ₂ -O) _n -H] ₂ , - [NHA ₂ ] X, -

[NA ₃ ] X, -SO ₃ H, - [SO ₃ ] X or 2H-benzotriazol-2-yl and

A is alkyl having 1 to 20 C atoms, n is an integer from 1 to 25,

Y and Z are each independently -ascorbyl, hydroxy, -O-2-ethylhexyl, -O-hexyl, -OA or -NH-C (CH ₃ ) ₃ and R ^{10 is} A, NA ₂ or

OA ¹ , wherein A ^{1 is} branched or linear C ₅ -C ₂ o-alkyl and with the proviso that at least one of R ³ or R ^{4 is} the radical B.

In a variant of the invention, compounds of the formula I are preferred when R ² in formula I denotes hydroxyl.

In a variant of the invention, compounds of the formula I are preferred when R ¹ in formula I denotes hydroxyl.

In a variant of the invention, compounds of the formula I are preferred when R ⁵ to R ⁹ , R ¹¹ and R ¹² in formula II are H.

In a variant of the invention, compounds of the formula I are particularly preferred when R ¹⁰ in formula II is NA ' ₂ . The invention likewise provides a process for the preparation of compounds of the formula I ₁ as described above, which comprises a) a compound of the formula III

wherein

R ¹ or R ^{2 have} one of the meanings given above for the formula I or preferably, directly with a compound of the formula IV

B-M IV

wherein B has one of the meanings described above, and

M alkali metal or alkaline earth metal cation or H, is reacted or

b) the hydroxy groups of the compound of the formula III, as described above, are protected to give a compound of the formula V,

wherein

R ¹ or R ^{2 have} one of the meanings described above for the formula I and SG is a protective group, in a subsequent step, the radicals R and / or R, if these

Hydroxy groups are protected by a second protecting group, which are again cleavable under other reaction conditions such as the protective group SG, the protecting groups SG of the compounds of the formula V are split off again and the resulting compound is reacted with a compound of the formula IV BM IV, where B has one of the meaning previously described for the formula I, and M is alkali metal or alkaline earth metal cation or H, and then the radicals R ¹ and / or R ² deprotected to the hydroxy group and optionally these hydroxy groups into another radical R ¹ or R ² ≠ OH, as described above, converts.

The direct esterification of the compounds of the formula III with compounds of the formula IV, if these are bonded via a carbonyloxy function, takes place in the presence of concentrated sulfuric acid and preferably under inert gas conditions. Advantageously, the mixture of components at temperatures <5 ° C is prepared. The actual reaction temperature is between 10 and 60 ^° C., preferably between 15 and 30 ^° C. Particularly preferably, the reaction takes place at room temperature.

The educts of the formulas III and IV are commercially available, for example, ascorbic acid, ascorbic acid phosphate, sodium and magnesium ascorbyl phosphate, ascorbic acid glucoside, 2- (4-dihexylamino-2-hydroxybenzoyl) benzoic acid or 2- (4-dipentylamino-2-hydroxybenzoyl) - Benzoic acid can be synthesized by methods which are described for example in the standard works such as Houben-Weyl, methods of organic chemistry, Georg Thieme Verlag, Stuttgart, under reaction conditions which are known and suitable for the reactions mentioned. One can also make use of known per se, not mentioned here variants. In the case of direct esterification, a mixture of ascorbic acid C-6 esters and ascorbic acid C-5 esters is produced by synthesis, as a rule the ascorbic acid C-6 ester predominates. Ascorbic acid C-6 esters are compounds of formula I wherein R ^{4 is} B. Ascorbic acid C-5 esters are compounds of formula I wherein R ^{3 is} B.

Of course, these mixtures are separable by methods known to those skilled in the art.

The alternative preparation of the compounds according to the invention is based essentially on a protective group chemistry of the hydroxyl groups of

Compounds of the formula III, as defined above, so that specifically

Esterification in position 5 and / or 6 of the Ascorbinsäuregrundkörpers can take place. However, the esterification with compounds of the formula IV can also be carried out without prior protection group chemistry, the reaction conditions being well known to the person skilled in the art.

The protecting groups are usually chosen to be different from one another so that they can be selectively cleaved (see: TW Greene, PGM Wuts, Protective Groups in Organic Chemistry, 2nd Ed., Wiley, New York 1991 or PJ Kocienski, Protecting Groups, 1st ed., Georg Thieme Verlag, Stuttgart - New York, 1994, H. Kunz, H. Waldmann in Comprehensive Organic Synthesis, Vol. 6 (eds. BM Trost, I. Fleming, E. Winterfeldt), Pergamon , Oxford, 1991, pp. 631-701).

The term "hydroxy protecting group" is also well known and refers to groups which are suitable for protecting a hydroxy group from chemical reactions. Typical of such groups are unsubstituted or substituted aryl, aralkyl, aroyl or acyl groups, and also alkyl groups, alkyl, aryl or aralkyl-silyl groups or O ₁ O- or O, S-acetals. The nature and size of the hydroxy protecting groups is not critical because they are removed after the desired chemical reaction or reaction sequence; preferred are groups with 1-20, in particular 1-10 C-atoms. Examples of hydroxy-protecting groups include aralkyl groups such as benzyl, 4-methoxybenzyl or 2,4-dimethoxybenzyl, aroyl groups such as benzoyl or p-nitrobenzoyl, acyl groups such as acetyl or pivaloyl, p-toluenesulfonyl, alkyl groups such as methyl or tert-butyl, but also allyl, Alkylsilyl groups such as trimethylsilyl

(TMS), triisopropylsilyl (TIPS), tert-butyldimethylsilyl (TBS) or triethylsilyl, trimethylsilylethyl, aralkylsilyl groups such as tert-butyldiphenylsilyl (TBDPS), cyclic acetals such as isopropylidene, cyclopentylidene, cyclohexylidene, benzylidene, p-methoxybenzylidene or o, p-dimethoxybenzylidene acetal, acyclic acetals such as tetrahydropyranyl (Thp), methoxymethyl (MOM), methoxyethoxymethyl (MEM), benzyloxymethyl (BOM) or methylthiomethyl (MTM). Particularly preferred hydroxy protecting groups are benzyl, acetyl, tert-butyl or TBS.

As starting material of the synthesis, preference is given to using ascorbic acid, the hydroxyl groups of which are protected in the 5- and 6-position by protecting groups SG, as described above, according to known methods to give compounds of the formula V. Advantageously, a cyclic protecting group is selected which effectively simultaneously protects both positions 5 and 6. Examples of compounds of the formula V are accordingly 5,6-isopropylidene, cyclopentylidene, cyclohexylidene, benzylidene, p-methoxybenzylidene or o, p-dimethoxybenzylidene ascorbate. Preference is given to using 5,6-isopropylidene ascorbate.

Subsequently, the hydroxy groups in position 2 and 3 are protected by means of protective groups as described above, advantageously an aralkyl group or an alkylsilyl group is selected, particularly preferably an aralkyl group, for example the benzyl group. After releasing the protected in the first step hydroxy groups is reacted with a compound of formula IV, wherein B and M have a meaning previously described.

When reacting with a compound of formula IV wherein M = H and B corresponds to partial formula II, the coupling reaction preferably takes place in the presence of a dehydrating agent, e.g. a carbodiimide such as dicyclohexylcarbodiimide (DCC), N- (3-dimethylaminopropyl) -N'-ethylcarbodiimide hydrochloride (EDC) or diisopropylcarbodiimide (DIC), further e.g. Propanephosphonic anhydride (see Angew. Chem. 1980, 92, 129), diphenylphosphoryl azide or 2-ethoxy-N-ethoxycarbonyl-1,2-dihydroquinoline, in an inert solvent, e.g. a halogenated hydrocarbon such as dichloromethane, an ether such as tetrahydrofuran or dioxane, an amide such as DMF or dimethylacetamide, a nitrile such as acetonitrile, in dimethyl sulfoxide or in the presence of these solvents, at temperatures between about -10 and 40, preferably between 0 and 30 °. The reaction time is between a few minutes and several days, depending on the conditions used.

Instead of compounds of the formula IV as defined above, it is also possible to use derivatives of the formula IV, preferably a preactivated carboxylic acid, or a carboxylic acid halide, a symmetrical or mixed anhydride or an active ester. Such residues for activating the carboxy group in typical acylation reactions are described in the literature (e.g., in the standard works such as Houben-Weyl, Methoden der organischen Chemie, Georg-Thieme-Verlag, Stuttgart). Activated esters are conveniently formed in situ, e.g. by addition of HOBt (1-hydroxybenzotriazole) or N-hydroxysuccinimide.

The reaction is usually carried out in an inert solvent, using a halide of the formula IV in the presence of a acid-binding agent, preferably an organic base such as triethylamine, dimethylaniline, pyridine, dimethylaminopyridine or quinoline.

Also, the addition of an alkali or alkaline earth metal hydroxide, carbonate or bicarbonate or other salt of a weak acid of

Alkali or alkaline earth metals, preferably potassium, sodium, calcium or cesium may be beneficial.

After the coupling and thus introduction of the active ingredient rest in the main body of ascorbic acid, the hydroxy groups are deprotected in position 2 and 3 and gives compounds of formula I, wherein R ¹ and R ^{2 are} hydroxy. The conversion of these hydroxy groups into other radicals R ¹ and R ² , as defined above, is possible by standard methods.

The ascorbic acid derivatives described are capable of binding to textiles or textile fibers and thus unfolding their respective effect on the remainder B, for example UVA protection.

The ascorbic acid derivatives according to the invention, wherein the radical B is a substituent which absorbs UVA radiation and has a conjugated π-electron system of at least 4 π-electrons, with the partial structure of the formula II, for example, also anti-aging effects and have those of ascorbic acid derived benefits to the skin, ie, they serve for example, the skin regeneration and cause wrinkle reduction of (light) aged skin, for example, they further increase the skin relief density or enhance, for example, the dermis epidermis compound (papillae index). They protect the skin from UV-induced damage or, for example, have a skin-bleaching effect. For example, they have an antibacterial effect, ie they can reduce sweat odor or improve the appearance of skin blemishes and / or acne.

The ascorbic acid derivatives according to the invention, where the radical B is a substituent which absorbs UVA radiation and has a conjugated π-

Electron system of at least 4 π-electrons, with the partial structure of the formula II, are able to bind to hair and can thus prevent the UVArLicht caused by oxidation or hair damage, especially with regard to color and morphology. For example, you can protect it from fading hair.

An electron system of at least 4 π-electrons, having the partial structure of formula II, are capable of bonding not only to nitrogen-containing but also to sulfur-containing hair functionalities, e.g. to thiol groups. Due to the good reduction properties of the compounds, the ascorbic acid derivatives according to the invention can be used, for example, by controlled reduction of disulfide bridges, in hair treatment products for de-crimping or in the formation of perms.

EP 1728501 describes the use of UVA photoprotective filters bound to a polypeptide. Analogously to the teaching of EP 1728501, the ascorbic acid derivatives according to the invention, wherein the radical B is a substituent which absorbs UVA radiation and has a conjugated π-electron system of at least 4 π-electrons and corresponds to the partial structure of the formula II, can be used before application an amino acid, a

Peptide or a protein or be linked to an amino acid, a peptide or a protein. A further subject of the present invention is, according to the preferred use of the compounds according to the invention as a skin and / or hair-binding UV filter, an agent, for example a cosmetic, dermatological or pharmaceutical preparation or composition containing at least one compound of the formula I,

in which

R ¹ or R ^{2 are} each independently hydroxy, -O-alkyl, -OC (O) -

Alkyl, -OPO ₃ M or O-glycosyl,

Alkyl C 1 -C ₂₀ -alkyl,

M alkali or alkaline earth metal cation or H,

R ³ or R ^{4 are} each independently hydroxy or a radical B and

B is a substituent of the formula II,

in which

R ⁵ to R ⁹ and R ¹¹ to R ^{12 are} each independently H, -OH, -OA, -A,

-NH ₂ , -NHA, -NA ₂ , -NH- (CH ₂ -CH ₂ -O) _n -H, -Nl (CH ₂ -CH ₂ -O) _n -H] ₂ , - [NHA ₂ ] X , -

[NA ₃ ] X, -SO ₃ H, - [SO ₃ ] X or 2H-benzotriazol-2-yl and

A is alkyl having 1 to 20 C atoms, n is an integer from 1 to 25, X is the counterion to the cations [NHA ₂ ] ⁺ and [NA ₃ J ⁺ or the anion [SO ₃ ] ^" and

R ¹⁰ in the formula II is A, NA ' ₂ or OA ¹ , where A' is branched or linear C ₅ -C ₂₀ -alkyl, more preferably having at least five contiguous carbon atoms, with the proviso that at least one of the radicals R ³ or R ^{4 is} the radical B is.

The number n stands for an integer from 1 to 25, preferably for an integer of 1, 2, 3, 4 or 5.

X describes the counterion for the cations [NHA ₂ ] ⁺ and [NA ₃ J ⁺ , where A has one of the meanings given above, preferably Cl ^" , Br ^' , I ^" or [SO ₄ ] ^{2 "} or the counterion of the anion [ SO ₃ ] ^" , preferably an ammonium ion or an alkali metal or alkaline earth metal cation such as Na ⁺ , K ⁺ , Mg ²⁺ or Ca ²⁺ .

Compounds of formula I can also be used as salts according to the invention, i. At least one hydroxy group of the ascorbic acid skeleton is deprotonated and the charge is balanced by a counter cation, for example an alkali or alkaline earth metal cation.

Advantages of the compounds or preparations according to the invention are in particular in addition to the absorbing effect as a UVA filter, the Antioxidant effect, which unfolds in the functionalization of the matrix by disintegration of the Ascorbinsäuregrundkörpers, optionally the Selbstbräunerwirkung resulting from the Maillardreaktion and in particular the functionalization of the matrix which in the active ingredient B of the partial formula II in the compounds of formula I of an immobilization of the Active substance and thus, for example, an immobilized UVA protection equivalent.

However, the compounds according to the invention also have a structurally related antioxidant effect.

For the purposes of the present invention, the term preparation or formulation is used synonymously.

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

The compounds of formula I are used according to the invention typically in amounts of 0.01 to 20 wt .-%, preferably in amounts of 0.05 wt .-% to 10 wt .-%. The expert does not have any difficulties in selecting the quantities according to the intended effect of the preparation.

The agents according to the invention preferably contain as little oxygen as possible, ie the agents should be prepared under inert gas conditions. Furthermore, it is advantageous to keep the water content low. It is also advantageous to limit the presence of (heavy) metal ions, as they are known to destabilize antioxidants. Thus, the agents according to the invention may contain, for example, complexing agents. During production and also during storage, the substances according to the invention and the agents containing the substances according to the invention should be protected from UV radiation, light and heat. When the agents contain water, the pH should preferably be made acidic. All measures in this regard are known in the art.

However, the protective effect against oxidative stress or against the action of free radicals can be further improved if the agents or preparations according to the invention contain one or more further antioxidants, wherein the expert does not encounter any difficulties in selecting suitable fast or delayed-acting antioxidants.

There are many known and proven substances known from the literature which can be used as antioxidants, eg amino acids (eg glycine, histidine, tyrosine, tryptophan) and their derivatives, imidazoles, (eg urocaninic acid) and their derivatives, peptides such as D, L- Carnosine, D-carnosine, L-carnosine and their derivatives (eg anserine), carotenoids, carotenes (eg α-carotene, β-carotene, lycopene) and their derivatives, chlorogenic acid and its derivatives, lipoic acid and derivatives thereof (eg dihydrolipoic acid), Aurothioglucose, propylthiouracil and other thiols (eg thioredoxin, glutathione, cysteine, cystine, cystamine and their glycosyl, N-acetyl, methyl, ethyl, propyl, amyl, butyl and lauryl, palmitoyl, oleyl , γ-linoleyl, cholesteryl and glyceryl esters) and their salts, dilauryl thiodipropionate, distearyl thiodipropionate, thiodipropionic acid and derivatives thereof (esters, ethers, peptides, lipids, nucleotides, nucleosides and salts) and sulfoximine compounds (eg buthionine sulfoximines, Homocysteine sulfoximine, buthionine sulfone, penta-, hexa-,

Heptathioninsulfoximin) in very low tolerated dosages (eg pmol to μmol / kg), furthermore (metal) chelators, (eg α-hydroxy fatty acids, palmitic acid, phytic acid, lactoferrin), α-hydroxy acids (eg citric acid, lactic acid, malic acid), humic acid, bile acid

Bile extracts, bilirubin, biliverdin, EDTA, EGTA and their derivatives, unsaturated fatty acids and their derivatives, vitamin C and derivatives (eg ascorbyl palmitate, magnesium ascorbyl phosphate, ascorbyl acetate), tocopherols and derivatives (eg vitamin E acetate), vitamin A and derivatives (eg vitamin A palmitate) and benzylic benzylic resin, rutinic acid and its derivatives, α-glycosylrutin, ferulic acid, furfurylidene glucitol, carnosine, butylhydroxytoluene, butylated hydroxyanisole,

Nordohydroguajaretsäure, Trihydroxybutyrophenon, Quercitin, uric acid and its derivatives, mannose and its derivatives, zinc and its derivatives (eg ZnO, ZnSO ₄ ), selenium and its derivatives (eg

Selenium methionine), stilbenes and their derivatives (e.g., stilbene oxide, trans-stilbene oxide).

Suitable antioxidants are also compounds of the general formula In A / or B

wherein

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

X is O or NH,

R ^{2 is} linear or branched alkyl having 1 to 30 C atoms,

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

R ^{5 is} linear or branched alkyl having 1 to 8 C atoms or linear or branched alkoxy having 1 to 8 C atoms and

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

¹ ^ dimethoxybenzy) malonic acid-bis (2-ethylhexyl) ester (example RonaCare ^® AP).

Mixtures of antioxidants are also suitable for use in the compositions or preparations according to the invention. Known and commercial mixtures mixtures are, for example, containing, as active 15 ingredients, lecithin, L - (+) - ascorbyl palmitate and citric acid (for example (for example Oxynex ^® AP), natural tocopherols, L - (+) - ascorbyl palmitate, L - (+) - ascorbic acid and citric acid (for example Oxynex K LIQUID ^®) tocopherol extracts from natural sources, L - (+) - ascorbyl palmitate, L - (+) -

Ascorbic acid and citric acid (for example Oxynex ^® L LIQUID), DL-α-

20

Tocopherol, L - (+) - ascorbyl palmitate, citric acid and lecithin (e.g.

Oxynex ^® LM) or butylhydroxytoluene (BHT), L - (+) - ascorbyl palmitate and citric acid (eg Oxynex ^® 2004). Such antioxidants are usually used with compounds of the formula I in such compositions in ratios in the range from 1000: 1 to 1: 1000, preferably in amounts of from 100: 1 to 1: 100.

The compositions or preparations according to the invention may contain vitamins as further ingredients. Preference is given to vitamins and vitamin derivatives selected from vitamin A, vitamin A propionate, vitamin A

OU

Palmitate, Vitamin A acetate, Retinol, Vitamin B, Thiamin chloride hydrochloride (Vitamin Bi), Riboflavin (Vitamin B ₂ ), Nicotinic acid amide, Vitamin C (Ascorbic acid), vitamin D, ergocalciferol (vitamin D ₂ ), vitamin E, DL-α-tocopherol, tocopherol-E-acetate, tocopherol hydrogen succinate, vitamin Ki, esculin (vitamin P active ingredient), thiamine (vitamin Bi), nicotinic acid ( Niacin), pyridoxine, pyridoxal, pyridoxamine, (vitamin B ₆ ), pantothenic acid, biotin, folic acid and cobalamin (vitamin B1 ₂ ) in the cosmetic preparations according to the invention, particularly preferred retinol, nicotinamide, vitamin A palmitate, vitamin C and its Derivatives, DL-α-tocopherol, tocopherol-E-acetate, nicotinic acid, pantothenic acid and biotin, most preferably retinol or nicotinamide. Vitamins are usually used with compounds of the formula I in ratios in the range from 1000: 1 to 1: 1000, preferably in amounts of 100: 1 to 1: 100.

Particularly preferred agents or preparations according to the invention contain, in addition to the compounds of the formula I, also pure UV filters.

In principle, all UV filters are suitable for combination with the compounds of the formula I according to the invention. Particularly preferred are those UV filters whose physiological harmlessness has already been demonstrated. These UV filters are usually incorporated in an amount of 0.5 to 20 weight percent, preferably 1-15 wt .-%, in cosmetic formulations.

For both UVA and UVB filters, there are many known and proven substances in the literature, e.g.

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

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

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

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

Trimethylcyclohexyl salicylate (e.g., Eusolex® HMS),

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

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

and other substances like

2-ethylhexyl 2-cyano-3,3-diphenylacrylate (eg Eusolex® OCR), 3,3 ^' - (1,4-phenylenedimethylene) bis- (7,7-dimethyl-2-oxobicyclo- [2.2 .1] hept-1-ylmethanesulfonic acid and its salts (eg Mexoryl ^® SX) and - 2,4,6-trianilino- (p-carbo-2 ^{^{'-ethylhexyl-1'}} -oxi) -1, 3,5-triazine (for example Uvinul ^® T 150)

- 2- (4-diethylamino-2-hydroxy-benzoyl) -benzoic acid hexyl ester (Uvinul ^® example UVA Plus, BASF.).

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

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

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

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

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

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

In general, by encapsulation of individual UV filters or other ingredients preparation problems caused by interaction of individual preparation components with each other, such as

Crystallization processes, precipitation and agglomeration are avoided because the interaction is suppressed.

Therefore, it is preferred according to the invention if one or more of the abovementioned UV filters are present in encapsulated form. It is advantageous if the capsules are so small that they can not be observed with the naked eye. To achieve the o.g. Effects, it is still necessary that the capsules are sufficiently stable and the encapsulated

Active ingredient (UVA filter) not or only to a small extent to the environment.

Suitable capsules may have walls of inorganic or organic polymers. For example, US Pat. No. 6,242,099 B1 describes the preparation of suitable capsules having walls of chitin, chitin derivatives or polyhydroxylated polyamines. Capsules which are particularly preferred for use in accordance with the invention have walls which are formed by a SolGel process, as described in applications WO 00/09652, WO 00/72806 and WO 00/71084 can be obtained. Again, capsules whose walls are made up of silica gel (silica, undefined silicon oxide hydroxide) are preferred. The preparation of such capsules is known to the expert, for example, from the cited patent applications, whose contents are expressly also to

Subject of the present application belongs.

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

The compositions or preparations according to the invention may additionally contain further anti-aging active ingredients, anti-cellulite active ingredients or customary skin-friendly or skin-care active ingredients. Skin-sparing or skin-care active ingredients can, in principle, be all active ingredients known to the person skilled in the art.

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

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

Ectoine and ectoine derivatives such as hydroxyectoine may be beneficial in

Medicaments are used. In particular, hydroxyectoine can be used for the manufacture of a medicament for the treatment of skin diseases. Other uses of hydroxyectoine and other ectoine derivatives are typically in areas where e.g. Trehalose is used as an additive. Thus, ectoine derivatives, such as hydroxyectoine, can be used as a protective substance in dried yeast and bacterial cells. Also pharmaceutical products such as non-glycosylated, pharmaceutically active peptides and proteins e.g. t-PA can be protected with Ectoin or its derivatives.

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

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

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

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

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

Known anti-aging substances are also chromones, as described, for example, in EP 1508327 or retinoids, for example retinol (vitamin A), retinoic acid, retinaldehyde or else synthetically modified compounds of vitamin A. The described chromones and retinoids are also effective anti-cellulite agents. Another well known anti-cellulite drug is caffeine.

The agents may include, contain, or consist essentially of the stated necessary or optional ingredients or limitations. Any compounds or components that can be used in the compositions or preparations are either known and commercially available or can be synthesized by known methods.

One or more compounds of the formula I can be incorporated in the usual way into cosmetic or dermatological preparations. Suitable preparations for external use, for example as a cream, lotion, gel, or as a solution that can be sprayed on the skin.

As an application form 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 applications are e.g. Sticks, shampoos and shower baths. Any customary carrier substances, adjuvants and optionally further active ingredients can be added to the preparation.

Preferable excipients come from the group of preservatives, stabilizers, solubilizers, colorants, odor improvers.

Ointments, pastes, creams and gels may contain the usual excipients, for example animal and vegetable fats, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc and zinc oxide or mixtures of these substances. Powders and sprays may contain the usual excipients, for example lactose, talc, silicic acid, aluminum hydroxide, calcium silicate and polyamide powder or mixtures of these substances. Sprays may additionally contain the customary propellants, for example chlorofluorohydrocarbons, propane / butane or dimethyl ether.

Solutions and emulsions may contain the usual excipients such as solvents, solubilizers and emulsifiers, e.g. Water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1, 3-butyl glycol, dimethyl capramide, dimethyl isosorbide, oils, especially cottonseed oil, peanut oil, corn oil, olive oil, castor oil and sesame oil, glycerol fatty acid esters, polyethylene glycols and Fatty acid esters of sorbitan or mixtures of these substances. In a preferred application, the ascorbic acid derivatives according to the invention, as described, are converted into an application-appropriate formulation shortly before application. For example, the substance is dissolved in a carrier as described above and applied directly to skin or preferably to hair. Particularly suitable carriers in this sense are Arlasolve DMI (dimethylisosorbide), butylene glycol, Finsolv® PG-22 (dipropylene glycol dibenzoate) or Pelemol® BIP (butylphthalimide isopropylphthalimide).

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

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

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

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

Other typical cosmetic application forms are also lipsticks, lip balm, mascara, eyeliner, eye shadow, rouge, powder, emulsion and wax make-up and sunscreen, pre-sun and after-sun preparations.

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

Emulsions of the invention are advantageous and contain z. As mentioned fats, oils, waxes and other fatty substances, and water and an emulsifier, as it is commonly used for such a type of preparation. The lipid phase can advantageously be selected from the following substance group:

- mineral oils, mineral waxes

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

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

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

The oil phase of the emulsions, oleogels or hydrodispersions or lipodispersions in the context of the present invention is advantageously selected from the group of esters of saturated and / or unsaturated, branched and / or unbranched alkanecarboxylic acids having a chain length of 3 to 30 carbon atoms and saturated and / or unsaturated, branched and / or unbranched alcohols having a chain length of from 3 to 30 carbon atoms, from the group of esters of aromatic carboxylic acid and saturated and / or unsaturated, branched and / or unbranched alcohols having a chain length of from 3 to 30 carbon atoms. atoms. Such ester oils can then be advantageously selected from the group

Isopropyl myristate, isopropyl palmitate, isopropyl stearate, isopropyl oleate, n-butyl stearate, n-hexyl laurate, n-decyl oleate, isooctyl stearate, isononyl stearate, isononyl isononanoate, 2-ethylhexyl palmitate, 2-ethylhexyl laurate, 2-hexadecyl stearate, 2-octyldodecyl palmitate, oleyl oleate, oleyl erucate, acyl oleate, Erucylerucat and synthetic, semi-synthetic and natural mixtures of such esters, eg. B. jojoba oil. Furthermore, the oil phase can be advantageously 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 the fatty acid triglycerides, namely the triglycerol esters of saturated and / or unsaturated, branched and / or unbranched alkanecarboxylic acids having a chain length of 8 to 24, in particular 12-18 C-atoms , The fatty acid triglycerides can be advantageously selected from the group of ■ ^• synthetic, semi-synthetic and natural oils, eg. Olive oil,

Sunflower oil, soybean oil, peanut oil, rapeseed oil, almond oil, palm oil, coconut oil, palm kernel oil, and the like.

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

Advantageously, the oil phase is selected from the group 2-ethylhexyl isostearate,

Octyldodecanol, isotridecyl, isoeocosane, 2-ethylhexyl cocoate, C _{_2-15} alkyl benzoate, caprylic capric triglyceride, dicapryl.

Particularly advantageous are mixtures of Ci ₂ -i ₅ -Alkylbenzoat and

2-Ethylhexylisostearat, mixtures of Ci ₂ -i ₅ -Alkylbenzoat and Isotridecylisononanoat and mixtures of Ci ₂ -i ₅ -Alkylbenzoat, 2-ethylhexyl isostearate and Isotridecylisononanoat.

Of the hydrocarbons, paraffin oil, squalane and squalene are to be used advantageously in the context of the present invention. Advantageously, the oil phase can also have a content of cyclic or linear silicone oils or consist entirely of such oils, although it is preferred to use an additional content of other oil phase components in addition to the silicone oil or silicone oils.

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

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

If appropriate, the aqueous phase of the preparations according to the invention advantageously contains alcohols, diols or polyols of low C number, and their ethers, preferably ethanol, isopropanol, propylene glycol, glycerol, ethylene glycol, ethylene glycol monoethyl or monobutyl ether, propylene glycol monomethyl, monoethyl or monobutyl ether, diethylene - Glykolmonomethyl- or -monoethylether and analogous products, also low C-number alcohols, z. As ethanol, isopropanol, 1, 2-propanediol,

Glycerol and in particular one or more thickeners, which or which can be advantageously selected from the group silicon dioxide, aluminum silicates, polysaccharides or their derivatives, for example hyaluronic acid, xanthan gum, hydroxypropylmethylcellulose, particularly advantageous from the group of polyacrylates, preferably a polyacrylate from the group of Carbopols, for example Carbopols of types 980, 981, 1382, 2984, 5984, in each case individually or in combination. In particular, mixtures of the abovementioned solvents are used. For alcoholic solvents, water can be another ingredient.

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

In a preferred embodiment, the preparations according to the invention contain hydrophilic surfactants.

The hydrophilic surfactants are preferably selected from the group of alkylglucosides, acyl lactylates, betaines and cocoamphoacetates.

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

wherein R represents a branched or unbranched alkyl radical having 4 to 24 carbon atoms and wherein DP means a mean Glucosylierungsgrad of up to 2. The value DP represents the degree of glucosidation of the alkylglucosides used in the invention and is defined as

P 1 P 2 P 3 Pi

DP = 1 + 2 + 3 + ... = Σ /

100 100 100 100

Here pi, p ₂ , P3 ••• or pi represent the proportion of single, double-triple ... i-fold glucosylated products in weight percent. According to the invention are advantageous products with Glucosylierungsgraden of 1-2, particularly advantageously of 1, 1 to 1, 5, very particularly advantageous from 1, 2-1, 4, in particular selected from 1, 3.

The value of DP takes account of the fact that alkylglucosides generally represent mixtures of mono- and oligoglucosides as a result of the preparation. According to the invention, a relatively high content is advantageous

Monoglucosides, typically of the order of 40-70% by weight.

Alkylglylcosides used particularly advantageously according to the invention are selected from the group consisting of octylglucopyranoside, nonylglucopyranoside, decylglucopyranoside, undecylglucopyranoside, dodecylglucopyranoside, tetradecylglucopyranoside 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). In turn, the acyl lactylates are advantageously selected from the group of substances which are defined by the structural formula

CH,

I ³

R ¹ -CO-CH IIo oo

M®, wherein R ^{1 is} a branched or unbranched alkyl radical with

1 to 30 carbon atoms and M ⁺ from the group of

Alkali ions and the group of substituted with one or more alkyl and / or substituted with one or more hydroxyalkyl radicals ammonium ions or is equivalent to half an equivalent of an alkaline earth metal.

For example, sodium is advantageous, for example the product Pathionic ^® ISL from the American Ingredients Company.

The betaines are advantageously selected from the group of substances which are defined by the structural formula

characterized in that R ^{2 is} a branched or unbranched alkyl radical having 1 to 30 carbon atoms.

Particularly advantageously, R ^{2 is} a branched or unbranched alkyl radical having 6 to 12 carbon atoms. It is advantageous for example capramidopropylbetaine, for example the product Tego ^® betaine 810 from Th. Goldschmidt AG.

5

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

10

The preparations according to the invention are advantageously characterized in that the hydrophilic surfactant or surfactants in concentrations of 0.01-20 wt .-%, preferably 0.05-10 wt .-%, particularly preferably 0.1-5 wt .-%, respectively based on the total weight of the composition, is present or present. 15

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. 20

Cosmetic and dermatological preparations according to the invention can be present in various forms. So they can z. As a solution, an anhydrous preparation, an emulsion or microemulsion

_e . water-in-oil (W / O) or oil-in-water (O / W) type, a multiple emulsion, for example of the Waser-in-oil-in-water (W / O / W) type, a gel, a solid stick, an ointment or even an aerosol. It is also advantageous to present Ectoine in encapsulated form, e.g. In collagen matrices and other common encapsulation materials,

^ _n z. As encapsulated cellulose, in gelatin, wax matrices or liposomally encapsulated. In particular, wax matrices as described in DE-OS 43 08 282 have proved to be beneficial exposed. Preference is given to emulsions. O / W emulsins are especially preferred. Emulsions, W / O emulsions and O / W emulsions are available in the usual way.

As emulsifiers, for example, the known W / O and O / W

Emulsifiers are used. It is advantageous to use further customary co-emulsifiers in the preferred O / W emulsions according to the invention.

According to the invention are advantageous as co-emulsifiers, for example

O / W emulsifiers selected, mainly from the group of substances with HLB values of 11-16, very particularly advantageous with HLB values of 14.5-15.5, provided that the O / W emulsifiers saturated radicals R and R ¹ have. If the O / W emulsifiers have unsaturated radicals R and / or R ', or if isoalkyl derivatives are present, the preferred HLB value of such emulsifiers may also be lower or higher.

It is advantageous to choose the fatty alcohol ethoxylates from the group of ethoxylated stearyl alcohols, cetyl alcohols, cetylstearyl alcohols (cetearyl alcohols). Particularly preferred are: polyethylene glycol (13) stearyl ether (steareth-13), polyethylene glycol (14) stearyl ether (steareth-14), polyethylene glycol (15) stearyl ether (steareth-15), polyethylene glycol (16) stearyl ether (steareth-16), Polyethylene glycol (17) stearyl ether (steareth-17), polyethylene glycol (18) stearyl ether (steareth-18), polyethylene glycol (19) stearyl ether (steareth-19), polyethylene glycol (20) stearyl ether (steareth-20), polyethylene glycol (12) isostearyl ether (isosteareth-12), polyethylene glycol (13) isostearyl ether (isosteareth-13), polyethylene glycol (14) - isostearyl ether (isosteareth-14), polyethylene glycol (15) isostearyl ether (isosteareth-15), polyethylene glycol (16) isostearyl ether (isosteareth- 16), polyethylene glycol (17) isostearyl ether (isosteareth-17), polyethylene glycol (18) isostearyl ether (isosteareth-18), polyethylene glycol (19) isostearyl ether (isosteareth-19), polyethylene glycol (20) - isostearyl ether (isosteareth-20), polyethylene glycol (13) cetyl ether (ceteth-13), polyethylene glycol (14) cetyl ether (ceteth-14), polyethylene glycol (15) - cetyl ether (ceteth-15), polyethylene glycol (16) cetyl ether (ceteth-16), polyethylene glycol (17) 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) oleylet (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) cetyl stearyl ether (Ceteareth-13 ), Polyethylene glycol (14) cetyl stearyl 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 of the following group:

Polyethylene glycol (20) stearate, polyethylene glycol (21) stearate,

Polyethylene glycol (22) stearate, polyethylene glycol (23) stearate,

Polyethylene glycol (24) stearate, polyethylene glycol (25) stearate, Polyethylene glycol (12) isostearate, polyethylene glycol (13) isostearate, polyethylene glycol (14) isostearate, polyethylene glycol (15) isostearate, polyethylene glycol (16) isostearate, polyethylene glycol (17) isostearate, polyethylene glycol (18) isostearate, polyethylene glycol (19) isostearate,

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

As the ethoxylated alkyl ether carboxylic acid or its salt, the sodium laureth-11-carboxylate can be advantageously used. As the alkyl ether sulfate, sodium laureth-4 sulfate can be advantageously used. As the ethoxylated cholesterol derivative, polyethylyl glycol (30) cholesteryl ether can be advantageously used. Also polyethylene glycol (25) soybean oil has been proven. As ethoxylated triglycerides, the polyethylene glycol (O) Evening Primrose Glycerides can advantageously be used (Evening Primrose = evening primrose).

It is furthermore advantageous to use the polyethylene glycol glycerol fatty acid esters from the group consisting of polyethylene glycol (20) glyceryl laurate, polyethylene glycol (21) glyceryl laurate, polyethylene glycol (22) glyceryl laurate, polyethylene glycol (23) glyceryl laurate, polyethylene glycol (6) glyceryl caprate / citrate, polyethylene glycol (20) glyceryl oleate, polyethylene glycol (20) glyceryl isostearate, polyethylene glycol (18) glyceryl oleate (cocoate).

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

As optional, but according to the invention optionally advantageous W / O emulsifiers can be used:

Fatty alcohols containing 8 to 30 carbon atoms, monoglycerol esters of saturated and / or unsaturated, branched and / or unbranched alkanecarboxylic acids having a chain length of 8 to 24, in particular 12-18, carbon atoms, diglycerol esters of saturated and / or unsaturated, branched and / or unbranched alkanecarboxylic acids a chain length of 8 to 24, in particular 12-18 C-atoms, monoglycerol ethers of saturated and / or unsaturated, branched and / or unbranched alcohols

Chain length of 8 to 24, in particular 12-18 C-atoms, diglycerol ethers of saturated and / or unsaturated, branched and / or unbranched alcohols of a chain length of 8 to 24, in particular 12-18 C-atoms, propylene glycol esters of saturated and / or unsaturated, branched and / or unbranched alkanecarboxylic acids having a chain length of 8 to 24, in particular 12-18 carbon atoms and sorbitan esters of saturated and / or unsaturated, branched and / or unbranched alkanecarboxylic acids having a chain length of 8 to 24, in particular 12-18, carbon atoms.

Particularly advantageous W / O emulsifiers are glyceryl monostearate,

Glyceryl monoisostearate, glyceryl monomyristate, glyceryl monooleate, Diglyceryl monostearate, Diglycerylmonoisostearat, propylene glycol monostearate, propylene glycol monoisostearate, propylene glycol monocaprylate, propylene glycol monolaurate, sorbitan monoisostearate, sorbitan monolaurate, sorbitan monocaprylate, Sorbitanmonoisooleat, sucrose distearate, cetyl alcohol, stearyl alcohol, arachidyl alcohol, behenyl alcohol, Isobehenyl- alcohol, selachyl alcohol, chimyl alcohol, polyethylene glycol (2) stearyl ether (steareth 2), glyceryl monolaurate, glyceryl monocaprinate, glyceryl mono- caprylate or PEG-30 dipolyhydroxystearate.

The compositions or preparations described are particularly useful for protecting human skin against UV radiation, aging processes and oxidative stress, i. against damage by radicals. They are present in various dosage forms commonly used for this application. Thus, the preparation in particular as a lotion or emulsion, such as cream or milk (O / W, W / O, O / W / O, W / O / W), in the form of oily-alcoholic, oily-aqueous or aqueous-alcoholic Gels or solutions, be present as solid pens or formulated as an aerosol.

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

Dyes used are preferably approved dyes listed in the Cosmetics Regulation, Appendix 3 as a positive list.

Preservatives which are preferably used as preservatives are those described in the Cosmetics Ordinance, Annex 6 listed as a positive list or antimicrobial pigments, as described for example in WO 2004/0092283 or WO 2004/091567.

Suitable preservatives are therefore also alkyl esters of p-

Hydroxybenzoic acid, hydantoin derivatives, propionate salts or a variety of ammonium compounds.

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

Emollients or plasticizers are often incorporated into cosmetic preparations. They are preferably used in 0.5 to 50% by weight, preferably between 5 and 30% by weight, based on the total composition. In general, plasticizers can be classified into classes, such as the category of esters, fatty acids or fatty alcohols,

Polyols, hydrocarbons and oils containing at least one amide structure unit.

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

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

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

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

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

Further emollients or hydrophobizing agents are preferably C ₁₂ to C ₅ alkyl benzoates, dioctyl adipate, octyl stearate, octyl dodecanol, hexyl laurate, octyl dodecyl neopentanoate, cyclomethicones, dicapryl ethers, dimethicones, phenyltrimethicones, isopropyl myristate, capriylic / capric glycerides, propylene glycol dicaprylate / dicaprate or decyl oleate.

Another category of functional ingredients of cosmetic preparations in the context of the invention are thickeners.

Thickeners are usually in quantities between 0.1 to 20

Wt .-%, preferably between 0.5 to 10 wt .-% based on the Total used. Exemplary of these compounds are crosslinked polyacrylate materials, available commercially under the Carbopol brand from BF Goodrich Company. It is also possible to use thickeners, such as xanthan gum, carrageenan gum, gelatin gum, karaya gum, pectin gum or locust bean gum.

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

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

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

Other preferred embodiments are oily lotions based on natural or synthetic oils and waxes, lanolin, fatty acid esters, especially triglycerides of fatty acids, or lower alcohol based oily alcohol lotions such as ethanol, or a glycerol such as propylene glycol, and / or a polyol such as Glycerol, and oils, waxes and fatty acid esters, such as triglycerides of fatty acids. The preparation or agent of the invention may also be in the form of an alcoholic gel comprising one or more lower alcohols or polyols, such as ethanol, propylene glycol or glycerin, and a thickener, such as silica. The oily-alcoholic gels also contain natural or synthetic oil or wax.

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

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

The cosmetic preparation may also be used to protect the hair against photochemical damage to prevent changes in hues, discoloration or damage of a mechanical nature. In this case, it is suitably carried out as a shampoo, lotion, gel or emulsion for rinsing, wherein the respective preparation is applied before or after shampooing, before or after dyeing or decolouring or before or after perming. It is also possible to choose a preparation as a lotion or gel for hairdressing and treatment, as a lotion or gel for brushing or laying a wave of water, as hair lacquer, perming agent, dyeing or decolorizing the hair. The composition having photoprotective properties may contain, in addition to the compound or compounds of formula I, various adjuvants used in this type of mediator, such as surfactants, thickeners, polymers, emollients, preservatives, foam stabilizers, electrolytes, organic solvents, silicone derivatives, oils, waxes, antifatting agents , Dyes and / or pigments which dye the agent itself or the hair or other ingredients commonly used for hair care.

Further objects of the present invention are a process for preparing a composition as described above, characterized in that in that at least one compound of the formula I is mixed with a carrier and optionally with further active or auxiliary substances. The present invention also provides a process for the preparation of a preparation, which is characterized in that at least one compound of the formula I is mixed with radicals as described above with a cosmetically, pharmaceutically or dermatologically suitable carrier.

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

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

Examples:

List of abbreviations used:

Aq. equivalent

DCC dicyclohexylcarbodiimide

DMAP dimethylaminopyridine

DMSO dimethyl sulfoxide

EDC N- (3-dimethylaminopropyl) -N'-ethyl-carbodiimide hydrochloride

EE vinegar

EG ethylene glycol sat. saturated conc. concentrated

1N HCl 1N hydrochloric acid i-PrOH isopropanol

Solution. Solution

MeCN acetonitrile

MTBE methyl t-butyl ether org. organic

RT room temperature

Hour

T temperature

THF tetrahydrofuran

Example 1A:

Synthesis of 2- (4-Dihexylamino-2-hydroxybenzoyl) benzoic acid (R) -2-

((R) -3,4-dihydroxy-5-oxo-2,5-dihydro-furan-2-yl) -2-hydroxy-ethyl ester (or synonymously 2- (4-dihexylamino-2-hydroxybenzoyl) -benzoic acid, ascorbyl ester )

Vitamin C (24.8 g, 140.9 mmol, 4 eq.) Is poured into 37.8 ml conc. In an argon-purged apparatus. Sulfuric acid added in portions. The internal temperature is kept below 5 ° C by ice-cooling. Subsequently, 15 g of 2- (4-dihexylamino-2-hydroxybenzoyl) benzoic acid (35.2 mmol, 1 eq.) Also at T <5 ° C added in portions. Thereafter, 15.6 ml of oleum are added dropwise at T <15 ⁰ C. After 6 hrs. Reaction time at 4O ⁰ C, the reaction solution is poured onto 350 ml of ice water. It is extracted with 2 x 250 ml MTBE. To Dry over sodium sulfate, the solvent is removed in vacuo. The product is obtained as a yellow foam (15.64 g, 76%).

In the reaction, the synthesis of the compound 2- (4-dihexylamino-2-hydroxy-benzoyl) benzoic acid (R) -1 - ((R) -3,4-dihydroxy-5-oxo-2, 5-dihydro -furan-2-yl) -2-hydroxyethyl ester.

Stability data:

Prepared cosmetic preparations with a constant content of in each case 1% of the compounds of the formula I according to the invention, for example 2- (4-Dihexylylamino-2-hydroxy-benzoyl) benzoic acid (R) -2-

((R) -3,4-dihydroxy-5-oxo-2,5-dihydro-furan-2-yl) -2-hydroxy-ethyl ester

The recovery of the UV filters measured after the preparation of the cosmetic formulation is measured.

Human stratum corneum was used as substrate with a 1% ethanolic solution of 2- (4-dihexylylamino-2-hydroxybenzoyl) benzoic acid (R) -2 - ((R) -3,4-dihydroxy-5-oxo 2,5-dihydro-furan-2-yl) -2-hydroxyethyl ester incubated for 6h. Thereafter, the substrate was washed with ethanol to give unbound 2- (4-dihexylylamino-2-hydroxybenzoyl) benzoic acid (R) -2 - ((R) -3,4-dihydroxy-5-oxo-2, 5-dihydro-furan-2-yl) -2-hydroxy-ethyl ester. Following was the substrate hydrolyzed. The hydrolyzate was measured photometrically. The obtained absorbance value corresponded to the bound portion of 2- (4-dihexyllylamino-2-hydroxybenzoyl) benzoic acid (R) -2 - ((R) -3,4-dihydroxy-5-OXO-2, 5 -d ihydrofuran-2-yl) -2-hydroxypropyl-ethyl ester.

Antioxidant activity:

Basis for the determination of the antioxidant efficacy is the so-called DPPH test as in Bünger et. al. [Buenger, J., Ackermann, H., Jentzsch, A., Mehling, A., Pfizner, I., Ripening, K.-A., Schroeder, K.-R., and Wollenweber U., An interlaboratory comparison of methods used to assess antioxidant potentials, Int. J. Cosm. Sci., 28 (2006) 1-12]. The Antioxidant Activity of 2- (4-Dihexylylamino-2-hydroxybenzoyl) benzoic acid (R) -2- ((R) -3,4-dihydroxy-5-oxo-2,5-dihydro-furan-2 -yl) -2-hydroxyethyl ester is determined in the DPPH test.

Example 1 B. ^¬ Synthesis of 2- (4-dipentylamino-2-hydroxy-benzoyl) -benzoic acid 2- (3,4-dihydroxy-5-oxo-2,5-dihydro-furan-2-yl) -2 hydroxy-ethyl ester

A)

10 g of 5,6-isopropylidene-ascorbate (46.3 mmol, 1 eq., Available from Merck-Schuchardt: 8.18234) are dissolved in 30 ml of THF and 35 ml of DMSO, 19.2 g of potassium carbonate are added and 13 ml of benzyl bromide (110 mmol, 2.4 eq.). After 3 hrs. At 50 ⁰ C, the gas evolution is complete. The solid is filtered off and extracted 3 times with 100 ml of ethyl acetate. The combined organic phases are dried over sodium sulfate and the solvent removed in vacuo. The product is obtained almost quantitatively without further purification.

B)

The doubly benzyl-protected 5,6-isopropylidene-ascorbate is dissolved in 65 ml of THF and 30 ml of 2N HCl added slowly at room temperature. After 48 hours, 150 ml of MTBE and solid sodium chloride are added to saturation and extracted. The organic phase is dried over sodium sulfate and the solvent removed in vacuo. The product is obtained almost quantitatively without further purification.

C)

The doubly benzyl-protected ascorbate (2.14 g, 6 mmol, 1 eq.) From step B) is treated with DMAP (73 mg, 0.6 mmol, 0.1 eq.) And 1.88 g of 2- (4- Dipentylamino-2-hydroxybenzoyl) benzoic acid (6 mmol, 1 eq.) Dissolved in 11 ml acetonitrile in an argon-purged flask. Add portionwise at 0 ⁰ C then EDC (9 mmol, 1.5 eq 1, 7 g.). It is warmed to RT and after 22 hours, the solvent removed in vacuo. The residue is washed with 50 ml of ethyl acetate and 50 ml of 1 N NaOH solution. recorded and extracted. The org. Phase is then with 2 x 50 ml of 1 N HCl and 1 x 50 ml sat. NaCl solution. extracted The organic phase is dried over sodium sulfate and the solvent removed in vacuo. The product is obtained after filtration through silica gel.

D)

The educt from stage C) is dissolved in ethyl acetate and reduced under 1-5 bar hydrogen pressure with Pd-C catalyst. After filtration of the catalyst, the product is purified by filtration through silica gel.

Example 1 C:

Analogously to Example 1 B are prepared:

2- (4-Di [2-ethylhexyl] amino-2-hydroxy-benzoyl) -benzoic acid 2- (3,4-dihydroxy-5-oxo-2,5-dihydrofuran-2- yl) -2-hydroxypropyl-ethyl ester of the double-benzyl-protected ascorbate with 2- (4-di- [2-ethylhexyl] amino-2-hydroxybenzoyl) benzoic acid and subsequent debenzylation:

The doubly benzyl-protected ascorbate (25 g, 70.2 mmol, 1 eq.) As in Example 1B, step B) is treated with DMAP (875 mg, 7 mmol, 0.1 eq.) And 50.7 g of 2- (2). Dissolve 4-di (2-ethylhexyl) amino-2-hydroxybenzoyl) benzoic acid (105.2 mmol, 1.5 eq.) In an argon-purged flask in 125 mL of acetonitrile. Then at ⁰ ° C., the DCC (21.7 g, 105.2 mmol, 1.5 eq.) Is added portionwise. It is warmed to RT and after 22 hours, the solvent removed in vacuo. The residue is washed with 50 ml of ethyl acetate and 50 ml of 1 N NaOH solution. recorded and extracted. The org. Phase is then saturated with 2 x 50 ml of saturated NH ₄ Cl and 1 x 50 ml. NaCl solution. Extracted. The organic phase is dried over sodium sulfate and the solvent removed in vacuo. The product is obtained after filtration through silica gel as a light yellow oil.

The product from stage C) is dissolved in 250 ml of acetonitrile and reduced under 5 bar hydrogen pressure with 5 g of Pd-C catalyst. After filtration of the Catalyst, the product is purified by filtration through silica gel. The product is a yellow oil.

Example 1 D:

2- (4-Di [n-octyl] amino-2-hydroxybenzoyl) benzoic acid 2- (3,4-dihydroxy-5-oxo-2,5-dihydro-furan-2-yl) -2- hydroxyethyl ester by enzymatic esterification:

10 g of L-ascorbic acid (56.8 mmol, 1 eq.) Are initially charged in 190 ml of acetone with 10 g of molecular sieve 4 A, 100 mg of lipase (eg Rhizomucor miehei, recombinant from Aspergillus oryzae) and then 72.9 g of 2- (4-Di [n-octyl] amino-2-hydroxybenzoyl) benzoic acid (151.4 mmol, 2.67 eq.). After 16 hours reaction time at 37 ° C, the molecular sieve is filtered off, cooled to room temperature and the product precipitated by the slow addition of 100 ml of water. After drying in vacuo at 60 ⁰ C 2- (4-di [n-octyl] amino-2-hydroxy-benzoyl) benzoic acid 2- (3,4-dihydroxy-5-oxo-2,5-dihydro -furan-2-yl) -2-hydroxyethyl ester as a light yellow solid.

Example 1E:

2- (4-Di-laurylamino-2-hydroxy-benzoyl) -benzoic acid 2- (3,4-dihydroxy-5-oxo-2,5-dihydro-furan-2-yl) -2-hydroxy-ethyl ester enzymatic esterification:

10 g of L-ascorbic acid (56.8 mmol, 1 eq.) Are initially charged in 250 ml of ethyl methyl ketone with 10 g of molecular sieve 4 A, 150 mg of lipase (for example Candida cylindracea) and then 124.4 g of 2- (4-dicarboxylic acid). laurylamino-2-hydroxybenzoyl) benzoic acid (152 mmol, 2.67 eq.). After 14 hours reaction time at 37 ° C, the molecular sieve is filtered off, cooled to room temperature and the product by the slow addition of 125 ml of water and cooling to 5 ⁰ C deposited. After drying in vacuo at 60 ⁰ C to give 2- (4-di-laurylamino-2-hydroxy-benzoyl) benzoic acid 2- (3,4-dihydroxy-5-oxo-2,5-dihydro-furan-2 -yl) -2-hydroxyethyl ester as a light yellow oil.

The following example describes formulations for cosmetic preparations:

Example 2: W / O emulsion

Production: PELEMOL ^® GDP Arlasolv DMI and emulsifiers are presented. 2- (4-Dihexylylamino-2-hydroxybenzoyl) benzoic acid (R) -2 - ((R) -3,4-dihydroxy-5-oxo-2,5-dihydro-furan-2-yl) -2-hydroxy-ethyl ester and Uvinul ^® A Plus are dissolved therein. The remaining components of the oil phase are added and mixed homogeneously. With stirring, the adjusted to pH = 4-5 water phase is emulsified. Subsequently, it is homogenized. The emulsions can be prepared under mild conditions at room temperature. By increasing the content of ascorbic acid, 2- (4-dihexylylamino-2-hydroxy-benzoyl) -benzoic acid- (R) -2- ((R) -3,4-dihydroxy-5-oxo-2, 5- dihydrofuran-2-yl) -2-hydroxypropoxylate. Ideally, the production is carried out under inertization (exclusion of oxygen).

Example 3: Waterproof sunscreen spray

Preparation: The components of phase A are combined at room temperature and stirred until a clear solution is obtained. Subsequently, phase B is mixed and added with stirring to phase B. Continue stirring until finally the clear product is present. To the addition of antioxidants such as Oxynex ^® ST Liquid, RonaCare ^® AP or ascorbyl the stability of the substances of the invention can be increased.

Example 4: Pump Hairspray

Preparation: Pre-dissolve phase A until a clear solution is obtained. Add phase B to phase A with stirring. Premix phase C and add to the rest, stirring until a homogeneous mixture has formed.

Example 5: W / O Emulsions

Example 6: Hair Care Formulation

Example 7: Hair Care Formulation

Example 8: O / W emulsions

Example 9: O / W emulsions

Example 10: O / W emulsions

Example 11: Hydrodisperions (lotions and sprays)

Example 12: Aqueous and aqueous / alcoholic formulations

Example 13: Cosmetic foams

Claims

Patentansprϋche

1. Use of at least one ascorbic acid derivative for the functionalization of matrices, characterized in that at least one ascorbic acid derivative of the formula I

corresponds, where

R ¹ or R ^{2 are} each independently of one another hydroxy, -O-alkyl, -OC (O) -alkyl, -OPO ₃ M or O-glycosyl, alkyl C ₁ -C ₂ O-AlCl yI,

M alkali or alkaline earth metal cation or H,

R ³ or R ^{4 are} each independently of one another hydroxy or a radical B and B is a substituent of the formula II,

in which

R ⁵ to R ⁹ and R ¹¹ to R ^{12 are} each independently H, -OH, -OA,

-A, -NH ₂ , -NHA, -NA ₂ , -NH- (CH ₂ -CH ₂ -O) _n -H, -N [(CH ₂ -CH ₂ -O) _n -H] ₂ , -

[NHA ₂ ] X, - [NA ₃ ] X, -SO ₃ H, - [SO ₃ ] X or 2H-benzotriazol-2-yl, and

A is alkyl having 1 to 20 C atoms, n is an integer from 1 to 25, X is the counterion to the cations [NHA ₂ ] ⁺ and [NAa] ⁺ or the anion [SO ₃ ] ^" and

Y and Z are each independently -ascorbyl, hydroxy, -O-2-ethylhexyl, -O-hexyl, -OA or -NH-C (CH ₃ ) ₃ and R ^{10 is} A, NA ' ₂ or OA ¹ , wherein A 'is branched or linear C ₅ -C ₂₀ AlkyJ, with the proviso that at least one of R ³ or R ^{4 is} the radical B.

2. Use according to claim 1, characterized in that the matrix is skin, hair or nails.

3. Use according to claim 1 or 2, characterized in that R ² in formula I is hydroxy.

4. Use according to claim 1 to 3, characterized in that R ¹ in formula I is hydroxy.

5. Uses according to one or more of claims 1 to 4, characterized in that R ¹⁰ in formula II NA ₂ means.

6. Compounds of the formula I

in which

R ¹ or R ^{2 are} each independently of one another hydroxy, -O-alkyl, -OC (O) -alkyl, -OPO ₃ M or O-glycosyl,

AlkylCrC ₂ o-alkyl, M alkali or alkaline earth metal cation or H, R ³ or R ^{4 are} each independently hydroxy or a radical B and

B is a substituent of the formula II,

in which

R ⁵ to R ⁹ and R ¹¹ to R ^{12 are} each independently H, -OH, -OA, -A, -NH ₂ , -NHA, -NA ₂ , -NH- (CH ₂ -CH ₂ -O) _n - H, -N [(CH ₂ -CH ₂ -O) _n -H] ₂ , - [NHA ₂ ] X, - [NA ₃ ] X, -SO ₃ H, - [SO ₃ ] X or 2H-benzotriazole Mean 2-yl and

A is alkyl having 1 to 20 C atoms, n is an integer from 1 to 25,

X is the counterion to the cations [NHA ₂ ] ⁺ and [NA ₃ ] ⁺ or the anion

[SO ₃ ] ^' and Y and Z are each independently -ascorbyl, hydroxy, -O-2-ethylhexyl, -O-hexyl, -OA or -NH-C (CH ₃ ) ₃ and R ^{10 is} A, NA ₂ or OA ', where A' is branched or linear Cs-C _2O alkyl, with the proviso that at least one of R ³ or R ^{4 is} the radical B.

7. Compounds according to claim 6, characterized in that R ² in formula I is hydroxy.

8. Compounds according to claim 6 or 7, characterized in that R ¹ in formula I is hydroxy.

9. Compounds according to one or more of claims 6 to 8, characterized in that R ⁵ to R ⁹ , R ¹¹ and R ¹² in formula II are H.

10. Compounds according to one or more of claims 6 to 9, characterized in that R ¹⁰ in formula II is NA ' ₂ .

11. A process for the preparation of compounds according to one or more of claims 6 to 10, characterized in that a) a compound of formula III

wherein

R ¹ or R ^{2 have} a meaning described in claims 6 to 10, directly with a compound of formula IV

B-M IV

wherein B has a meaning described in claims 6 to 10 and

M is alkali metal or alkaline earth metal cation or H is reacted or b) the hydroxy groups of the compound of the formula III, as described above, are protected to give a compound of the formula V,

V wherein

R ¹ or R ^{2 have} a meaning described in claims 7 to 11, hereinafter the radicals R ¹ and / or R ² , if these are hydroxy groups, are protected by a second protective group, which are cleavable again under other reaction conditions such as the protective group SG , the protecting groups SG of the compounds of formula V again split off and the resulting compound with a compound of formula IV

BM IV, where B has the meaning described in claims 7 to 11 and M is alkali metal or alkaline earth metal cation or H, and then deprotected the radicals R ¹ and / or R ² as hydroxy group and optionally these hydroxy groups in another radical R ¹ or R ² ≠ OH converts.

12. Composition comprising at least one compound according to one or more of claims 6 to 10.

13. A composition according to claim 12, characterized in that it contains a cosmetically or pharmacologically acceptable carrier.

14. Composition according to claim 12 or 13, characterized in that the at least one compound of formula I is contained in amounts of 0.05 to 10% by weight.

15. Composition according to one or more of claims 12 to 14, characterized in that at least one further organic UV filter is included.

16. Composition according to one or more of claims 12 to 15, characterized in that at least one inorganic UV filter is included.

17. Composition according to one or more of claims 12 to 16, characterized in that at least one further ascorbic acid derivative, preferably from the group of ascorbic acid, Magnesiumascorbylphosphat or Ascorbylpalmitat, is included.

18. Composition according to one or more of claims 12 to 17, characterized in that at least one antioxidant is contained.

19. Composition according to one or more of claims 12 to 18, characterized in that at least one anti-aging active ingredient and / or at least one anti-cellulite active ingredient is included.

20. Composition according to one or more of claims 12 to 19, characterized in that at least one vitamin derivative is contained.

21. Composition according to one or more of claims 12 to 20, characterized in that at least one further adjuvant selected from the group of thickeners, emollients, humectants, surfactants, emulsifiers, preservatives, antifoaming agents, perfumes, waxes,

Lanolin, propellants, dyes and / or pigments which color the agent itself or the skin.

22. A process for the preparation of an agent according to one or more of claims 12 to 21, characterized in that at least one

A compound according to one or more of claims 6 to 10 a carrier and optionally mixed with other active or excipients.

23. Use of compounds of the formula I according to one or more of claims 6 to 10 as skin and / or hair-binding UV filters.