EP1265613A2 - Use of ectoin or ectoin derivatives for the prophylaxis and/or treatment of uv-induced immunosuppression - Google Patents

Abstract

The invention relates to the use of at least one compound selected from a compound of formula (1a, 1b), from a physiologically compatible salt thereof or from a stereoisomeric form thereof, wherein: R<1> represents H or alkyl; R<2> represents H, COOH, COO-alkyl or CO-NH-R<5>; R<3> and R<4>, independent of one another, represent H or OH; n is equal to 1, 2 or 3; R<5> represents H, alkyl, an amino acid radical, a dipeptide radical or a tripeptide radical, and; alkyl represents an alkyl radical with 1 to 4 carbon atoms. Said compound is used for the prophylaxis and/or treatment of UV-induced immunosuppression. According to the invention, these compounds are generally utilized in the form of a topical composition.

Description

 Use of ectoin or ectoin derivatives for the prophylaxis and / or treatment of

UV-induced immunosuppression

The present invention relates to the use of ectoin or ectoin derivatives for the prophylaxis and / or treatment of UV-induced immunosuppression

The skin, as the boundary layer and surface of the human body, is exposed to a variety of external stress factors.The human skin is an organ that protects the body from external factors with various types of cells, such as keratinocytes, melanocytes, Langerhans cells, Merkel cells and embedded sensory cells Protects influences Here a distinction must be made between external physical, chemical and biological influences on human skin. External physical influences include thermal and mechanical influences as well as the effects of radiation such as UV and IR radiation. The external chemical influences include in particular to understand the effects of toxms and allergens. The external biological influences include the effects of foreign organisms and their metabolic products. Other stress factors are pathological conditions and diseases such as fever, inflammation, infection and cell and tissue tetra uma, as well as physiological processes such as cell division

Human skin has a specific immunological defense system, the so-called skin immune system. In the area of the epidermis, Langerhans cells (LC) in particular are among the key cellular elements of the skin immune system, which has the task of protecting the human organism against harmful environmental influences, pathogens and transformed skin cells

A strong exposure of the human skin to the sun leads to a weakening of the skin's immune system, which is related in particular to the effect of UV-B radiation contained in sunlight and UV-A radiation close to UV-B. This phenomenon is known as UV-induced immunosuppression (ML Kπpke, Adv Cancer Res 34, 1981, 69-106) are the key cellular elements of the skin's immune system The epidermal LC in particular is affected by this UV-induced immunosuppression.About 2 to 4% of the epidermal cells are Langerhans cells, which are normally located in the suprabasal area of the epidermis and have a dental morphology. With their outlets, the so-called dentines, the LCs reach into the uppermost layers of the epidermis, such as the stratum granulosum, and form a dense, network-like network that runs through the entire epidermis.In addition to their morphology, the LC can also be characterized by the histological markers HLA-DR, CD1a, CD4 and membrane-based ATPase according to one Exposure to the sun or UV radiation leads to the following striking and significant changes in LC in human skin

The number of LCs is reduced depending on the UV dose applied. The LCs lose their dental morphology and become spherical. In addition, the LCs lose their ability to present antigen

A strong exposure to the sun therefore leads to immunosuppression in the skin

It is therefore the object of the present invention to eliminate or at least alleviate the above-mentioned problems and to provide a compound which is suitable for the prophylaxis and / or treatment of UV-induced immunosuppression

This object is achieved according to the invention by using at least one compound selected from a compound of the formula 1a, 1b,

a physiologically acceptable salt thereof or a stereoisomeric form thereof, wherein

R ^{1 is} H or alkyl,

R ² H, COOH, COO-alkyl or CO-NH-R ⁵ ,

R ³ and R ⁴ each independently of one another are H or OH,

n 1, 2 or 3,

R- H, alkyl, an amino acid residue, dipeptide residue or Tπpeptidrest, and

Alkyl is an alkyl radical having 1 to 4 carbon atoms

mean,

for the prophylaxis and / or treatment of UV-induced immunosuppression

Figure 1 shows a schematic overview of an experiment to demonstrate the effectiveness of ectoin in protecting Langerhans cells, as was carried out in Example 14 and Comparative Example 1

The compounds of the formulas 1 a and 1 b, the physiologically acceptable salts of the compounds of the formulas 1 a and 1 b and the stereoisomeric form of the compounds of the formulas 1 a and 1 b are also referred to below as “ectoine or ectoine derivatives”

Ectoin and the ectoin derivatives are low-molecular, cyc cal amino acid derivatives that can be obtained from various halophilic microorganisms. Both ectoin and ectoin derivatives have the advantage that they do not interfere with the cell metabolism. Ectoin and ectoin derivatives already become described in DE 43 42 560 as a moisturizer in cosmetic products The compounds used according to the invention can be present in the topical compositions as optical isomers, diastereomers, racemates, zwitterions, cations or as a mixture thereof

Preferred compounds used according to the invention are those in which R ^{1 is} H or CH ₃ , R ² H or COOH, R ³ and R ^{4 are} each independently H or OH and π 2. Of the compounds used according to the invention, the compounds (S) are -1 , 4,5,6-tetrahydro-2-methyl-4-pyπmιdιncarbonsaure (Ectoin) and (S, S) -1, 4,5,6-tetrahydro-5-hydroxy-2-methyl-4-pyπmιdιncarbonsaure (Hydroxyectom) particularly preferred

The term “amino acid” means the stereoisomeric forms, for example D and L forms, of the following compounds: alanine, β-alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, Glycm, histidm, isoleucine, leucine, lysm , Methionine, phenylalanine, Senn, Threonm, tryptophan, tyrosine, Vahn, γ-aminobutyrate, Nε-acetyllysine, Nδ-acetylomithine, Nγ-acetyldiaminobutyrate and N -acetyldiammobutyrate L-amino acids are preferred

Amino acid residues are derived from the corresponding amino acids

The residues of the following amino acids are preferably alanine, β-alanine, asparagine, aspartic acid, glutamine, glutamic acid, Glycm, Senn, Threonm Vahn, γ-aminobutyrate, Nε-acetyllysine, Nδ-acetylornithine, Nγ-acetyldiaminobutyrate and Nα-acetylate

The chemical nature of the di- and tπpeptide residues are acid amides and they break down into two or three amino acids during hydrolysis. The amino acids in the di- and tπpeptide residues are linked by amide bonds. Preferred di- and tπpeptide residues are made up of the preferred amino acids

The alkyl groups include the methyl group CH _3, the ethyl group C ₂ H ₅ , the propyl groups CH ₂ CH ₂ CH ₃ and CH (CH ₃ ) ₂ and the butyl groups CH ₂ CH ₂ CH ₂ CH ₃ , H ₃ CCHCH ₂ CH ₃ , CH ₂ CH (CH ₃ ) ₂ and C (CH ₃ ) ₃ The preferred alkyl group is the methyl group Preferred physiologically acceptable salts of the compounds used according to the invention are, for example, alkali metal, alkaline earth metal or ammonium salts, such as Na, K, Mg or Ca salts, and salts derived from the organic bases Tπethylamin or Tπs- (2-hydroxy-ethyl ) Amιn are derived. Further preferred physiologically acceptable salts of the compounds used according to the invention result from reaction with inorganic acids, such as hydrochloric acid, sulfuric acid and phosphoric acid, or with organic carboxylic or sulfonic acids, such as acetic acid, citric acid, benzoic acid, maleic acid, fumaric acid, tartaric acid and p -Toluolsulfonsaure

Compounds of the formulas 1a and 1b in which the same number of basic and acidic groups, such as carboxyl or amino groups, form internal salts

The preparation of the compounds used in the invention is described in

DE 4342 560 describes (S) -1, 4,5,6-tetrahydro-2-methyl-4-pyπmιdιn-carboxylic acid or (S, S) -1, 4,5,6-tetrahydro-5-hydroxy-2- methyl-4-pyπmιdιncarbonsaure can also be obtained microbiologically (Seveπn et al, J Gen Microb 138 (1992)

1629-1638)

According to the invention, ectoin or ectoin derivatives are usually used in the form of a topical composition

The topical composition is produced by at least one of the compounds used according to the invention, if appropriate, being brought into a suitable formulation with auxiliaries and / or excipients. The excipients and excipients come from the group of excipients, preservatives and other customary excipients

The topical compositions based on at least one compound used according to the invention are applied externally to the skin or the skin adnexa

Examples of solutions are solutions, suspensions, emulsions, pastes, ointments, gels, creams, lotions, powder soaps and surfactants Cleaning preparations, oils and sprays In addition to one or more compounds used according to the invention, any customary carrier substances, auxiliary substances and optionally further active substances are added to the composition

Preferred auxiliaries come from the group of preservatives, antioxidants, stabilizers, solubilizers, vitamins, colorants and odor improvers

In addition to one or more compounds used according to the invention, ointments, pastes, creams and gels can contain the usual carriers, for example animal and vegetable fats, waxes, paraffins, starches, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silica, talc and zinc oxide or mixtures of these substances

In addition to one or more compounds used according to the invention, powders and sprays can contain the usual carrier substances, e.g. milk sugar, talc, silica, aluminum hydroxide, calcium silicate and polyamide powder or mixtures of these substances. Sprays can also contain the usual blowing agents, e.g. chlorofluorocarbons, propane / butane or dimethyl ether

Solutions and emulsions can, in addition to one or more compounds used according to the invention, the usual carriers, such as solvents, solubilizers and emulsifiers, for example water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1, 3-butyl glycol, oils, in particular cotton isolaoles , Peanut oil, corn oil, olive oil, castor oil and sesamol, Glyceπnfettsaureester, polyethylene glycols and fatty acid esters of sorbitan or mixtures of these substances

In addition to one or more compounds used according to the invention, suspensions can contain the usual carriers, such as liquid diluents, for example water, ethanol or propylene glycol, suspending agents, for example ethoxylated isostearyl alcohols, polyoxyethylene sorbitol esters and polyoxyethylene sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar agar or tragacanth Substances In addition to one or more compounds used according to the invention, soaps can contain the usual carrier substances, such as alkali salts of fatty acids, salts of fatty acid semigestants, fatty acid protein hydrolysates, isothionates, lanolin, fatty alcohol, vegetable oils, plant extracts, glycerols, sugar or mixtures of these substances

In addition to one or more compounds used in accordance with the invention, surfactant-containing cleaning products can include the customary carrier substances, such as salts of fatty alcohol sulfates, fatty alcohol ether sulfates, sulfosuccinic acid semi-esters, fatty acid protein hydrolysates, isothionates, imidazolinium derivatives, methyl taurate derivatives, sarcosinates, fatty acid amide ether ethersulfates, fatty acid alkanol ether ethersulfates, fatty alcohol amide ether derivatives, fatty acid alkyl amide ether fatty acids, fatty acid alkyl amide ether fatty acids, fatty acid alkyl ether amides, fatty acid alkyl fatty amides, fatty acid alkyl amide ether fatty acids, fatty acid alkyl amide ether fatty acids, fatty acid alkyl amide ether fatty acids, fatty acid alkyl amide ether fatty acids, ethoxylated glycine fatty acid esters or mixtures of these substances

In addition to one or more compounds used according to the invention, facial and body oils can contain the customary carrier substances, such as synthetic oils, such as fatty acid esters, fatty alcohols, silicon icons, natural oils, such as vegetable oils and oily plant extracts, paraffinols, lanolinols or mixtures of these substances

Other typical cosmetic forms of use are also lipsticks, lip care sticks, mascara, eyeliner, eye shadows, blush, powder, emulsion and wax make-up as well as sunscreen, pra-sun and after-sun preparations

At least one compound used according to the invention is present in the topical composition and in an amount of preferably 0.0001 to 50% by weight, particularly preferably 0.001 to 10% by weight, particularly preferably 0.1 to 1% by weight, based on the composition

In addition to ectoin or the ectoin derivatives, at least one antioxidant and / or UV filter are preferably also used

According to the invention, the antioxidants known from the specialist literature can be used, for example flavonoids, coumaranones, amino acids (for example Glycm, histidine, Tyrosm, tryptophan) and their derivatives, imidazoles (for example urocanic acid) and their Derivatives, peptides such as D, L-Camosιn, D-Carnosin, L-Camosm and their derivatives (eg Anseπn), carotenoids, carotenes (eg α-carotm, β-carotm, lycopene) and their derivatives, chlorogenic acid and their Derivatives, lipoic acid and their derivatives (e.g. dihydroliponic acid), aurothioglucose, propylthiouracil and other thiols (e.g. thioredoxin, glutathione, system, cystine, cystamm and their glycosyl, N-acetyl, methyl, ethyl, propyl, amyl -, Butyl and lauryl, palmitoyl, oleyl, γ-linoleyl, cholesteryl and glyceryl esters) as well as their salts, diaurylthiodipropionate, distearylthiodipropionate, thiodipropioic acid and their derivatives (esters, ethers, peptides, lipids, nucleotides, nucleosides and salts) as well as sulfoxime compounds (e.g. buthionine sulfoxime, homocysteine sulfoxime, buthionine sulfones, penta-, hexa-, heptathionine sulfoxime), furthermore (metal) chelators (e.g. B -hydroxyfatty acid, palmitic acid, phytic acid, lactoferin), -hydric citric acid, , Humic acid, bile acid, Bile extracts, bilirubin, biliverdin, EDTA, EGTA and their derivatives, unsaturated fatty acids and their derivatives, vitamin C and derivatives (e.g. ascorbyl palmitate, magnesium ascorbyl phosphate, ascorbylacetate) as well as coniferyl benzoate of the benzoin resin, rutinic acid and its derivatives, α-glycosyl rutin Furfurylidene glucitol, carnosine, butylhydroxyltoluene (BHT), butylhydroxyanisole, nordohydroguajaretsaure, Tπhydroxybutyrophenon, uric acid and its derivatives, mannose and its derivatives, zinc and its derivatives (e.g. ZnO, ZnS0 ₄ ), selenium and its derivatives (e.g. selenium methane) their derivatives (e.g. stilbene oxide, trans-stilbene oxide)

Mixtures of antioxidants are also suitable. Known and commercially available mixtures are, for example, mixtures containing lecithin, L - (+) - ascorbyl palmate and citric acid (for example Oxynex ^® AP), natural tocopherols, L - (+) - ascorbyl palmate, L- as active ingredients. (+) - Ascorbic acid and citric acid (e.g. Oxynex ^® K LIQUID), tocopherol extracts from natural sources L - (+) - ascorbyl palmitate, L - (+) - ascorbic acid and citric acid (e.g. Oxynex ^® L LIQUID), DL-α- Tocopherol, L - (+) - ascorbyl palmate. Citric acid and lecithin (e.g. Oxynex ^® LM) or butylated hydroxytoluene (BHT), L - (+) - ascorbyl palmate and citric acid (e.g. Oxynex ^® 2004)

In a preferred embodiment of the invention, butylated hydroxytoluene is used as the antioxidant. In a further preferred embodiment, as Antioxidant one or more compounds selected from flavonoids and / or courmaranones used

The glycosides of flavanones, flavones, 3-hydroxyflavones (= flavanols), aurones, isoflavones and redoids are regarded as flavanoids (Rompp Chemie Lexikon, Volume 9, 1993). Within the scope of the present invention, however, the aglycones, ie the sugar-free constituents, are also included , and the derivatives of flavonoids and aglycones understood. In the context of the present invention, coumaranones also include their derivatives. Preferred flavonoids are derived from flavanones, flavones, 3-hydroxyflavones, aurones and isoflavones, in particular from flavanones, flavones, 3-hydroxyflavones and aurones , from

The flavanones are characterized by the following basic structure

The flavones are characterized by the following basic structure

The 3-hydroxyflavones (flavonols) are characterized by the following basic structure

The isoflavones are characterized by the following basic structure:

The Aurones are characterized by the following basic structure:

The coumaranones are characterized by the following basic structure:

The flavonoids and coumaranones are preferably selected from the compounds of the formula (I)

in what mean

Z _Ϊ to Z each independently of one another are H, OH, alkoxy, hydroxyalkoxy, mono- or oligoglycoside radicals, where the alkoxy and hydroxyalkoxy groups can be branched and unbranched and can have 1 to 18 carbon atoms and where the hydroxyl groups of the radicals mentioned can also contain sulfate or Phosphate can be bound

is selected from the group consisting of the partial forms (IA), (IB) and

Z ₅ H, OH or OR,

R is a mono- or oligoglycoside residue,

Z ₆ to Z _{0 have} the meaning of the radicals Z ^ to Z ₄ , and

The alkoxy groups are preferably linear and have 1 to 12, preferably

1 to 8 carbon atoms These groups thus correspond to the formula -0- (CH ₂ ) _m -H, where m

1, 2,3,4,5,6,7 or 8 and in particular 1 to 5 means

The hydroxyalkoxy groups are preferably linear and have 2 to 12, preferably 2 to 8 carbon atoms. These groups thus correspond to the formula -0- (CH ₂ ) _n -OH, where n _2, 3, 4, 5, 6, 7 or 8 , in particular 2 to 5 and particularly preferably 2

The mono- and oligoglycoside residues are preferably composed of 1 to 3 glycoside units. These units are preferably selected from the group of the hexosyl residues, in particular the rhamnosyi residues and glucosyl residues. However, other hexosyl residues, for example allosyl, altrosyl, gaiactosyl, gulosyl, idosyl, mannosyl and talosyl, are also if appropriate to be used advantageously It can also be advantageous according to the invention to use pentosyl radicals

In a preferred embodiment

Zi and Z ₃ mean H,

Z and Z _{4 have} a different meaning than H, in particular they mean OH,

Methoxy, ethoxy or 2-hydroxyethoxy, Z _{5 is} H, OH or a glycoside residue which is composed of 1 to 3, preferably 1 or 2, glycoside units Z ₆ , Z ₉ and Z10 have the meaning H, and

Z ₇ and Z _{8 have} a different meaning than H, in particular they mean OH,

Methoxy, ethoxy or 2-hydroxyethoxy

In a further preferred embodiment, in particular if the water solubility of the flavonoids and coumaranones is to be increased, a sulfate or phosphate group is bound to the hydroxyl groups. Suitable counterions are, for example, the ions of the alkali or alkaline earth metals, these being selected, for example, from sodium or potassium become

In a further preferred embodiment, the flavonoids are selected from the following compounds 4,6,3 '4'-tetrahydroxyauron, quercetin, rutin, isoquercetin, anthocyanidm (cyanidin), πodictyol, taxifolin, luteolm, tπshydroxyethylquercetin (Troxequercetm), Tπshinroxy Tπshydroxyethylisoquercetin (Troxeisoquercetm), Tπshydroxyethylluteolin (Troxeluteol) and their sulfates and phosphates

Among the flavonoids, rutin and troxerutin are particularly preferred. Troxerutin is particularly preferred

Preferred among the coumaranones is 4,6,3 ', 4'-tetrahydroxybenzylcoumaranon-3

According to the invention, the antioxidants are used in the topical composition in customary amounts

Furthermore, according to the invention, the UV filters known from the specialist literature can be used

Suitable organic UV filters are all UVA and UVB filters known to the person skilled in the art. For both UV areas there are many substances known and preserved from the specialist literature, for example benzylidene combat derivatives such as - 3- (4'-Methylbenzylιden) -dl-camphor (e.g. Eusolex ^® 6300),

- 3-benzyl-camphor (e.g. Mexoryl ^® SD),

- Polymers of N- ^< | (2 and 4) - [(2-oxobom-3-ylide) methyl] benzyl (e.g. Mexoryl ^® SW),

- N, N, N-Tπmethyl-4- (2-oxoborn-3-ylιdenmethyl) anιlιnιum methyl sulfate (eg Mexoryl ^® SK) or

α- (2-oxoborn-3-ylιdeπ) toluene-4-sulfonic acid (e.g. Mexoryl ^® SL),

Benzoyl or dibenzoyl methanes, such as

- 1 - (4-tert-Butylphenyl) -3- (4-methoxyphenyl) propane-1, 3-dion (e.g. Eusolex ^® 9020) or

- 4-lsopropyldιbenzoylmethan (for example Eusolex ^® 8020),

Benzophenones, like

- 2-Hydroxy-4-methoxybenzophenone (e.g. Eusolex ^® 4360) or

- 2-Hydroxy-4-methoxy-benzophenone-5-sulfonic acid and its sodium salt (e.g. Uvmul ^® MS-40),

Methoxycinnamate, such as

p-methoxyzιmtsaure-2-ethylhexyl ester (e.g. Eusolex ^® 2292),

p-methoxycinnamic acid isopentyl ester, eg as a mixture of the isomers (eg Neo Helιopan ^® E 1000),

Salicylatdeπvate, such as

- 2-ethylhexylsahcylate (e.g. Eusolex ^® OS),

- 4-Isopropylbenzylsalιcylat (eg Megasol ^® ) or

- 3,3,5-Tπmethylcyclohexylsalιcylat (e.g. Eusolex ^® HMS),

4-aminobenzoic acid and derivatives thereof, such as - 4-aminobenzoic acid,

4- (dimethylamino) 2-ethylhexyl benzoate (e.g. Eusolex ^® 6007),

- Ethoxylated ethyl 4-aminobenzoate (e.g. Uvinul ^® P25),

and other substances, such as

2-cyano-3,3-diphylacrylic acid 2-ethylhexyl ester (e.g. Eusolex ^® OCR),

- 2-Phenylbenzιmιdazol-5-sulfonic acid and its potassium, sodium and tπethanolamine salts (e.g. Eusolex ^® 232),

- 3,3 '- (1, 4-phenylenedimethylene) -bιs- (7,7-dimethyl-2-oxobιcyclo [2 2 1] hept-1 - ylmethanesulfonic acid and its salts (eg Mexoryl ^® SX) and

- 2,4,6-Tπanιlιno- (p-carbo-2'-ethylhexyl-1 '-oxι) -1, 3,5-trιazιn (e.g. Uvinul ^® T 150)

These organic UV filters are generally used in an amount of 0.5 to 10% by weight, preferably 1 to 8% by weight, in the topical composition used according to the invention

Other suitable organic UV filters are, for example

- 2- (2H-Benzotπazol-2-yl) -4-methyl-6- (2-methyl-3- (1, 3,3,3-tetramethyl-1 - (tπmethylsιlyloxy) dιsιloxanyl) propyl) phenol (e.g. Silatπzole ^® ),

- 4,4 '- [(6- [4 - ((1, 1-dimethylethyl) aminocarbonyl) phenylamino] -1, 3,5-tπazin-2,4-dimyl) dimin) dimin] bιs (2-ethylhexyl benzoate) (e.g. Uvasorb ^® HEB),

- α- (Tπmethylsιlyl) -ω [trιmethylsιlyl) oxy] poly [oxy (dιmethyl] [and approx. 6% methyl [2- [p- [2,2-bιs (ethoxycarbonyl] vinyl] phenoxy] -1-methyleneethyl] and ca 1.5% methyl [3- [p- [2,2-bιs (ethoxycarbonyl) vιnyl) phenoxy) - propenyl) and 0.1 to 0.4% (methylhydrogen] sιlylene]] (n ^ 60) (e.g. B Parsol ^® SLX,

- 2,2'-methylene-bιs- (6- (2H-benzotπazol-2-yl) -4- (1, 1, 33-tetramethyl- butyl) phenol (e.g. B ^® Tinosorb M),

- 2,2 '- (1,4-phenylene) bιs- (1 H-benzimidazole-4,6-disulfonic acid, mononate salt,

- 2,2 '- (1,4-phenylene) bιs- (1 H-benzιmιdazol-5-sulfonic acid, mononate salt, - 2,2 '- (1,4-phenylene) bιs- (1 H-benzιmιdazol-5-sulfonic acid, monoca salt and

- 2,4-bιs - {[4- (2-ethylhexyloxy) -2-hydroxyl] phenyl r - 6- (4-methoxyphenyl) -1, 3,5-tπazιn (e.g. Tinosorb ^® S )

These organic filters are generally used in an amount of 0.5 to 20% by weight, preferably 1 to 15% by weight, in the topical composition used according to the invention

Possible inorganic UV filters are those from the group of titanium dioxides, eg coated titanium dioxide (eg Eusolex ^® T-2000 or Eusolex ^® T-Aqua), zinc oxides (eg Sachtotec ^® ), iron oxides or cerium oxides. These inorganic UV Filters are generally used in an amount of 0.5 to 20% by weight, preferably 2 to 10% by weight, in the topical composition used according to the invention

Preferred UV filters are zinc oxide, titanium dioxide, 3- (4'-methylbenzylidene) -dl-camphor, 1 - (4-tert-butylphenyl) -3- (4-methoxyphenyl) propane-1, 3-dionone, 4-isopropyldibenzoyl - methane, 2-hydroxy-4-methoxybenzophenone, octyl methoxycinnamate, 3,3,5-trimethylcyclohexylsalyl cylate, 4- (dimethylamino) 2-ethylhexyl beπzoate, 2-cyano-3,3-diphenyl 2-ethylhexyl benzyl 2-ethylhexyl ester, 5-sulfonic acid and its potassium, sodium and tπethanolamine salts

Zinc oxide and titanium dioxide are particularly preferred UV filters

If titanium dioxide is used according to the invention, it is preferred that, in addition to titanium dioxide, one or more further UV filters selected from 3- (4'-methylbenzylidene) - dl-camphor, 1 - (4-tert-butylphenyl) -3- (4th -methoxyphenyl) propane-1, 3-dionon, 4-isopropyldιbenzoylmethane, 2-hydroxy-4-methoxybenzophenone, octyl methoxycinnamate, 3,3,5-tπmethylcyclohexyl salicylicate, 4- (dimethylamino) 3-2-ethylhexanoate, 2-ethylhexyl 3-Dιphenylacrylsaure- 2-ethylhexyl ester, 2-Phenylbenzιmιdazol-5-sulfonic acid and their potassium, sodium and Tπethanolaminsalze be used It is particularly preferred that, in addition to titanium dioxide, the UV filters 2-hydroxy-4-methoxybenzophenone and / or 2-ethylhexyl p-methoxycidate are also used

According to the invention, ectoin or ectoin derivatives can be used for the prophylaxis and / or treatment of UV-induced immunosuppression. The use of ectoin or ectoin derivatives according to the invention leads in particular to protection of Langerhans cells in the skin or ectoine derivatives preserve the dental morphology of the Langerhans cells and their ability to present antigen. Overall, UV-induced immunosuppression can thus be effectively avoided

The following examples illustrate the present invention. All compounds or components which can be used in the cosmetic formulations are either known and commercially available or can be synthesized by known methods

The INCI names of the raw materials used are as follows (the INCI names are specified in English by definition)

Raw material INCI name

Glyceπn Glyceπn

Paraffin, thin fluid Mineral Oil (Paraffinum Liquidum)

Mirasil CM 5 Cyclomethicone

Arlacel 165 glyceryl stearate, PEG-100 stearate

Germaben II Propylene Glycol, Diazolidmyl Urea, Methylparaben,

Propylparaben

Isopropyl Myπstat Isopropyl Myπstate

Water, demineralized aqua

Stearic acid steaπc acid example 1

Hair tonic with ectoin

RAW MATERIAL INCI% by weight

MERCARE ^® Biotin (D Biotin 0.05 Art No. 130220 MERCARE ^® Ectoin (Ectoin) 1, 00 Art No. 130200 Octopirox (2) Piroctone Olamme 0.10

D (+) Pantothenyl Alcoho! (3) Panthenol 0.30 (Art No. 501375) Salicylic acid d) Salicyhc Acid 0.10 (Art No. 100631) N-Cetyl-N, N, N-tπmethyl- d) Cetπmonium Bromide 0, 10 ammonium bromide (Art No. 102343) Dragoplant Hamamelis (4) Aqua, Alcohol Dentat, Hamamelis 1, 00 Virgmiana

2-propanol d) isopropyl alcohol 45.00

(Art-No 100995)

Demin water aqua ad 100

manufacturing

Biotin was dissolved in water and 2-propanol. Ectoin was then dissolved and the remaining raw materials were added with stirring

Bezuqsquellen

(1) Merck KGaA

(2) Max

(2) BASF

(3) Dragoco Example 2

2 in 1 shampoo

RAW MATERIAL INCI% by weight

Jaguar C-162 (2) hydroxypropyl guar 0.20 hydroxypropyltmonmonium chloride

Miranol Ultra C32 (2) Sodium Cocoamphoacetate 10.00

Texapon NSO (3) Sodium Laureth Sulfate 32.00

Nicotinamide (Vitamin B3) d) Niaciπamid 0.10

(Art No. 130179)

(D +) - Bιotιn (Vitamin H) d) Biotin 0.05

(Art No. 130220)

MERCARE ^® Ectoin d) (Ectoin) 1, 00

(Art no 130200

D-panthenol (4) panthenol 0.50

Sodium chloride d) Sodium chloride 1.0

(Art No. 106400)

Perfume perfume

Preservative q p

Citric acid d) Citπc Acid q s

(Art No. 130137)

Demm water aqua ad 100

manufacturing

Jaguar C-162 was dispersed in water and hydrated with citric acid. The remaining raw materials were added in the order given with stirring. Then the viscosity was adjusted with NaCl and the pH with citric acid

Where to Buy

(1) Merck KGaA

(2) Rhodia

(3) Cognis GmbH

(4) BASF AG Example 3

Hair styling gel

RAW MATERIAL Art. No. INCI wt.%

A

Pearlescent pigments (D 1, 00

Carbopol ETD 2001 (2) Carbomer 0.50

2-propanol z A 1 09634 (1) isopropyl alcohol 20.00

Water, demineralized Aqua (Water) 30.00

B

Luviskol K 30 powder (3) PVP 1, 60

Germaben II (4) propylene glycol, 0.20 diazolidinyl urea, methyl paraben, propyl paraben

Highly pure ethanolamine 108377 (Dthanolamine 1, 20

MERCARE ^® ECTOIN 130200 (D (Ectoin) 1, 00

Water, demineralized Aqua (Water) 45.60

manufacturing

The pearlescent pigment was dispersed in the water / propanol mixture of phase A and the Carbopol was sprinkled in with stirring. After complete dissolution, the pre-dissolved phase B was slowly stirred in

Remarks

Recommended pearlescent pigments are interference pigments, silver pigments, gold pigments, iron oxide pigments

Where to Buy

(1) Merck KGaA

(2) BF Goodrich GmbH (3) BASF AG

(4) ISP Global Technologies

Example 4

Svndet wash stucco

RAW MATERIAL INCI% by weight

Zetasap 813 A (2) disodium lauryl sulfosuccmate, 90.0

Sodium cocoyl isothionate,

Cetearyl alcohol, corn starch,

Glyceryl stearate, paraffin,

Titanium Dioxide

Ectoin (1) (Ectoin) 1, 00

(Art-No 130200)

Perfume Perfume 1.00

Demin Water Aqua (Water) 8.00

Bezugsguellen

(1) Merck KGaA

(2) Zschimmer & Schwarz

Example 5

shower gel

RAW MATERIAL Art. No. INCI wt.%

Timiron Splendid Green 1 17477 (1) Cl 77891 (Titanium Dioxide), 0.10

Mica, silica

Keltrol T (2) xanthan gum 0.75

Water, demineralized Aqua Water) 62.10

B

Plantacare 2000 (3) decyl glucoside 20.00 Texapon ASV (3) Magnesium Oleth Sulfate, 0.65 Sodium Oleth Sulfate, Magnesium Laureth-8 Sulfate, Sodium Laureth-8 Sulfate, Magnesium Laureth Sulfate, Sodium Laureth Sulfate

Bronidox L (3) Propylene Glycol 5-Bromo-5- 0.20 Nιtro-1, 3-dιoxane

Parfumol Everest 79658 SB (4) Perfume 0.05 MERCARE ^® Ectoin 130200 (1) (Ectoin) 1.00

C

Citric acid monohydrate 130137 (1) Citπcid 0.15 water, demineralized Aqua (Water) 10.00

Hersteilung

For phase A, the pigment was stirred into the water. Keltrol T was slowly sprinkled in with stirring and stirring was continued until dissolved. Phases B and C were added in succession, and stirring was continued until everything was homogeneously distributed

Where to Buy

(1) Merck KGaA

(2) Kelco

(3) Cognis GmbH

(4) Haanmann & Reimer GmbH

Example 6

baby powder

RAW MATERIAL Art. No. INCI wt.%

A

IR 3535 ™ 111887 (1) ethyl butyl acetylaminopropionate 4.00 B

Magnesium Hydroxide - 105827 (1) Magnesium Carbonate 10.00 carbonate hydroxides

Dry Flo PC (2) Aluminum Starch 86.00

Octenylsuccinate

MERCARE ® ¹ Ectoin 130200 (1) (Ectoin) 1, 00

manufacturing

Phase B was introduced and mixed with a propeller stirrer, phase A was added dropwise

Bezugsguellen

(1) Merck KGaA

(2) National Starch & Chemical

Example 7

OΛ / V After Sun Lotion

RAW MATERIAL Art. No. INCI wt.%

A

MERCARE ^® Bisabolol 130170 (D Bisabolol 0.30 Montanov 68 (2) Cetearyl Alcohol, 4.00 Cetearyl Glucoside

Miglyol 812, neutralol (3) Caprylic / Capπc Tπglyceπde 12.00 Mirasil CM5 (4) Cyclomethicone 2.00 Mirasil DM 350 (4) Dimethicone 1.00

B

Water, demineralized Aqua (Water) 77.20 Glyceπn (87% purest) 104091 (1) Glyceπn 3.00 Preservative qs MERCARE ^® Ectoin 130200 (1) (Ectoin) 1.00 C

Rhodicare-S (4) xanthan gum 0.50

manufacturing

Phases A and B were heated separately to 75 ° C, phase C was slowly added to B at 75 ° C with stirring and stirring was continued until a homogeneous mixture was obtained. Phase A was then added to the mixture B / C and homogenized with stirring the mixture obtained was cooled to room temperature

Bezugsguellen

(1) Merck KGaA

(2) Seppic

(3) Huls AG

(4) Rhodia GmbH

Example 8

Sun protection lotion (W / O)

RAW MATERIAL Art. No. INCI wt.

A

Eusolex 8300 105385 (1) 4-Methylbenzylιdene 4.00

Camphor

Eusolex 2292 105382 (D octyl methoxy cmnamate, 7.00 BHT

Abil WE 09 (2) polyglyceryl-4-isostearate, 5.00 cetyl dimethicone copolyol, hexyl laurate

Jojobaol (3) Buxus Chmensis (Jojoba Oil) 3.00

Cetiol V (4) decyl oleate 3.00

Pπsoπne 2021 (5) isopropyl isostearate 2.00

Paracera M (6) Microwax 1, 00

Miglyol 812, neutralol (7) Caprylic / Capπc Tπglyceπde 3.00

Propyl 4-hydroxybenzoate 1 07427 (1) Propylparaben 0.05 B

Eusolex T-Aqua 105401 (1) Aqua (Water), 16.00

Titanium Dioxide, Alumina, Sodium Metaphosphate, Phenoxyethanol, Sodium Methylparaben

Glyceπn (87% pure) 104091 (1) Glyceπn 2.00

Natπumchloπd 106400 (1) sodium chloride 0.40

MERCARE ^® Ectoin 130200 (1) (Ectoin) 1, 00

Water, demineralized Aqua (Water) 53.40

Methyl 4-hydroxybenzoate 106757 (1) methyl paraben 0.15

Herstellunq

Phase B was heated to 80 ° C. and phase A was heated to 75 ° C. Phase B was slowly stirred into phase A. The mixture was homogenized and cooled with stirring

Where to Buy

(1) Merck KGaA

(2) Th Goldschmidt AG

(3) Henry Lamotte GmbH

(4) Cognis GmbH

(5) Unichema Chemie GmbH

(6) Parameter

(7) Huls AG

Example 9

Tooth Gel

RAW MATERIAL Art. No. INCI wt.%

A

Sodium fluoride 106441 (1) sodium fluoride 0.06 canon F liquid 152698 (1) sorbitol 48.39 sodium benzoate 106290 (1) sodium benzoate 0.16 sodium saccharide 0.16

MERCARE ^® Ectoin 130200 (1) (Ectoin) 1, 00 water, demineralized Aqua (Water) 29.12 B

MERCARE ^® Olaflur 111680 (1) Olaflur, Propylene Glycol 1, 17 1 03281 bromochlorophene (1) Bromochlorophene 0.08 Flavor 35049 (2) 0.78

C

Polyethylene glycol 400 807485 d) PEG-8 2.34 Tego Betaine ZF (3) Cocamidopropyl Betaine 3.89 Sicomet Patent Blue (4) 0.62 (E131), 0.1% in water

D

Silent 12 (5) silica 7.40 Sipemat 22 S (5) hydrated silica 5.84

manufacturing

Phases A and B were separately premixed. Phase C was heated to 50 ° C. Phases A and B were stirred into Phase C and mixed under vacuum. After slow addition of Phase D, the mixture was homogenized under vacuum. The mixture was stirred under vacuum until the gel became clear was

Where to Buy

(1) Merck KGaA

(2) Cπssa Drebing GmbH

(3) Th Goldschmidt AG

(4) BASF AG

(5) Degussa AG

Example 10

Mouthwash Concentrate

RAW MATERIAL% by weight

MERCARE ^® Ectoin o: 1, 00 N-Cetylpyrιdιnιumchloπd (Art -Nr 102340) (1) 0.50 Ethanol (96%) (Art -Nr 100971) (1) 70.00 Peppermint Flavor 77526-34 (2) 0.15 Water, demineralized Ad 100, 00

manufacturing

All components were stirred until the solution was clear

Bezugsguellen

(1) Merck KGaA

(2) Givaudan-Roure, Dortmund

Example 11

lip salve

RAW MATERIAL INCI% w / o

Ectoin (1) (Ectoin) 1, 00

(Art-No 130200)

Tagat S2 (2) PEG-20 glyceryl stearate 10.00

Lanette O (3) Cetearyl Alcohol 20.00

Glyceπn (87%) (1) Glyceπn 20.00

(Art-No 104091)

Vaseline (4) petrolatum 35.00

manufacturing

All components were heated to 75 ° C. and then cooled to room temperature with stirring

Bezugsguellen

(1) Merck KGaA

(2) Goldschmidt GmbH (3) Cognis GmbH

(4) Schumann Sasol

Example 12

Lip gloss

RAW MATERIAL Art. No. INCI wt.%

A

Pearlescent pigments (D 10.00

B

Indopol H 100 (2) Polybutene 59.95 Bentone Gel MIO V (3) Quaternιum-18 Hectoπte, 20.00 Propylene Carbonate Paraffinum Liquidum (Mineral Oil)

Eutanol G (4) Octyldodecanol 6.00 MERCARE ^® 130180 (1) Tocopheryl Acetate 1, 00 Tocopherol Acetate 1, 00 Dow Corning 1403 Fluid (5) Dimethiconol, Dimethicone, 3.00 Propyl 4-hydroxybenzoate 1 07427 (1) Propylbarabene 0 , 05

MERCARE ^® Ectoin (1) (Ectoin) 1, 00

manufacturing

All components of phase B were weighed together, heated (60-70 ° C.) and stirred well until a homogeneous mass was obtained. Then phases B and C were added and the mixture was stirred again. The homogeneous mixture was filled at 50-60 ° C.

Bezugsguellen

d) Merck KGaA

(2) Amoco

(3) Rheox (4) Cognis GmbH

(5) Dow Corning

Example 13

Cold sore cream

RAW MATERIAL INCI% by weight

Ectoin (1) (Ectoin) 1, 00

(Art-No 130200)

Acyclovir (9 - [(2-hydroxyethoxy) - 5.00 methyl] guanιn)

Tagat S2 (2) PEG-20 glyceryl stearate 10.00

Lanette 0 (3) cetearyl alcohol 20.00

Glycenn (87%) Glycenn 20.00

(Art-No 104091)

Vaseline (4) petrolatum 35.00

Demm Wasser Aqua (Water) ad 100

manufacturing

All components were heated to 75 ° C. and then cooled to room temperature with stirring

Where to Buy

(1) Merck KGaA

(2) Goldschmidt GmbH

(3) Cognis GmbH

(4) Schumann Sasol Example 14 and Comparative Example 1

To demonstrate the effectiveness of the ectoin compounds, an O / W emulsion containing ectoin (Example 14) was examined for its cytoprotective effect on the number of Langerhans cells in UV-irradiated human skin, and with an ON \ l emulsion, which did not contain ectoin (Comparative Example 1), compared This experiment is shown schematically in Figure 1

Example 14:

A cream (O W) containing ectoin is produced from the following components

Wt%

A) Paraffin, low viscosity (Art. No. 107174) (1) 8.0

Isopropyl mypstat (Art -Nr 822102) (1) 4.0

Mirasil CM 5 (2) 3.0

Stearic acid (1) 3.0

Arlacel 165 V (3) 5.0

B) Glycenn, 87% (Art -Nr 104091) (D 3.0

Germaben II (4) 0.5

Water, demineralized ad 100

C) Ectoin (1) 1, 0

manufacturing

First, phases A and B are heated separately to 75 ° C. Thereafter, phase A is slowly added to phase B with stirring and stirred until a homogeneous mixture is obtained. After homogenization of the emulsion, the mixture is cooled to 30 ° C. with stirring C warmed, phase C added and stirred until homogeneous

Where to Buy

(1) Merck KGaA, Darmstadt (2) Rhodia

(3) ICI

(4) ISP

(5) Dragoco

Comparative Example 1:

A cream (O / W) without ectoin is made from the following components

Wt%

A) Paraffin, low viscosity (Art. No. 107174) (1) 8.0

Isopropyl mypstat (Art -Nr 822102) (1) 4.0

Mirasil CM 5 (2) 3.0

Stearic acid (1) 3.0

Arlacel 165 V (3) 5.0

B) Glycenn, 87% (Art-Nr 104091) (1) 3.0

Germaben II (4) 0.5

Water, demineralized ad 100

manufacturing

Phases A and B are heated separately to 75 ° C. Thereafter, phase A is slowly added to phase B with stirring and stirred until a homogeneous mixture is obtained

Where to Buy

(1) Merck KGaA, Darmstadt

(2) Rhodia

(3) ICI

(4) ISP

(5) Dragoco The investigation was carried out using the following devices and consumables

Equipment:

Name / type: Manufacturer:

Solar simulator SOL 500 with H2 filter Dr Honle

UVB measuring device Dr Honle

Kuhl / Gefπerschrank Bosch

C0 ₂ incubator Hera cell Heraeus

Vacuum pump ME2 Vacuumbrand

Vacuum measuring device Vacuumbrand

Custom made suction cup

Skin investigation and

Technology Hamburg GmbH

Vacuum distributor block custom-made

Skin investigation and

Technology Hamburg GmbH

Micropipettes 100-1000 μl Labsystems microscope CK40 Olympus microscope DXC-950 OP Olympus pipetting aid Pipetus battery Hirschmann Vortex Reaxtop Heidolph Libra AR61 Mettler Toledo

Consumables:

Designation / type: Manufacturer / order number:

Sterile tips for Greiner and Labsystems micropipettes

24-hole Greiner plates

Sigma cacodylate buffer Formaldehyde Merck KGaA

ATP sigma

MgS0 ₄ Merck KGaA

Pb (N0 ₃ ) ₂ Merck KGaA

Tπsmal buffer sigma

NaCI Sigma

Sucrose Merck KGaA

Ammonium sulfide solution Merck KGaA

PBS ² Gibco BRL

Mowiol Aldπch

subjects:

The subject group for the study was composed of 10 skin-healthy subjects (5 male and 5 female subjects, phototype ll-IV). The subjects had a mean age of 42.1 ± 11.4 years and an age distribution of 27.4 to 69, 7 years on

Prüfareale:

The two forearms of each test subject were divided into two 4 x 4 cm test areas. The test areas were no longer creamed from 48 hours before the start of the test and were not exposed to UV radiation for one week before the start of the test

Application:

Two of the test areas were treated twice daily with the corresponding creams according to Example 14 or Comparative Example 1 (approx. 2.0 mg / cm ² ) for a period of 14 days

Minimum erythema dose (MED):

To determine the individual minimum erythema dose (MED), each was based on the dermatological assessment of the subject's phototype Subject irradiated with a light staircase using a sun simulator. 6 areas on the lateral part of one of the two forearms (outside the test area) at a distance of approx. 20 to 25 cm from the radiation source with different irradiation times between 2 min 0 sec and 18 mm 38 sec, depending on Phototype of the subject, irradiated The irradiation tent was increased from area 1 to area 6. Thereafter, the test areas were treated with the appropriate cream according to Example 14 or Comparative Example 1. To determine the MED, the irradiated areas of the subjects were visual after 24 hours If a clear or moderate erythema on one or two of the six radiation areas was clearly verified after 24 hours, the test person was released and reappointed 13 days later for the radiation of the actual test areas. If the test person did not show any clear erythema, he was at the other Un Terarm laterally outside the test area with a light staircase with an increased dose, ie with a shorter distance to the radiation source and / or a longer radiation tent, again irradiated accordingly and after another 24 hours again visually assessed on the 6 radiation areas to evaluate the UV light-reduced skin changes Evaluation of the UV-light-induced erythema, the individual MED was determined for each subject

irradiation:

14 days after the start of the first application of the creams according to Example 14 or Comparative Example 1, a last application was carried out on the corresponding areas about 20 minutes before the irradiation of the test areas. Then the three test areas provided were irradiated (one untreated and the two with one each) Cream (areas treated according to Example 14 or Comparative Example 1) with a dose of 15 MED. The dose was defined by varying the distance from the forearm to the radiation source and by the duration of the radiation. An untreated fourth test area remained unirradiated as a control. To avoid edge effects, each test area was irradiated individually (ie, only an area of 4 x 4 cm in size per forearm) Preparation of the suction bladders:

48 hours (± 2 hours) after the start of the previous irradiation, one suction cup, which had a clear opening of 5 mm, was fastened to the test areas by means of plaster strips. A vacuum of 750 to 700 mbar was created under the suction cups within 2 to 2.5 hours of small suction bubbles with a diameter of approx. 5 mm. The bladder roofs were wrapped sterile using a surgical cutlery and briefly collected in cold physiological buffer solution until further use (ATPase staining)

ATPase staining:

The bladder roofs of the suction bladders obtained in this way were used for the investigations.The preparations were subjected to a color procedure in 24-hole tissue culture plates in a volume of 1.0 ml per well. The preparation (suction bladder roof) was briefly rinsed in PBS in the first step Preparation incubated for 20 minutes at 4 ° C in 0.2 M cacodylate buffer. This was followed by 3 rinsing steps in 0.9% NaCl solution at 4 ° C (total time approx. 10 min). The preparation was then in for 30 minutes at 37 ° C a color solution, which was obtained by mixing 10 mg ATP in 5 ml 10% MgSO solution with 3 ml 2% Pb (NO ₃ ) ₂ solution and 42 ml 0.2 M Tπsmal buffer, followed by incubation a double rinse with 0.9% NaCl solution at 4 ° C for 5 minutes each. The subsequent incubation in a 1% ammonium sulfide solution led to the formation of a dark PbS precipitate. Finally, twice at 4 ° C for a total of 5 minutes sp ult (PBS) and the preparation then transferred to a slide and capped with a drop of PBS. The capping medium was obtained by dissolving 1 g of Mowiol in 3 ml of PBS while heating

The number of stained Langerhans cells in a preparation was determined by microscopic evaluation and the cell numbers obtained in Langerhans cells per mm ² converted Tables I and II summarize the cell numbers thus determined of the corresponding test areas of each subject Microscopic evaluation:

4 suction bladder preparations were obtained per subject and analyzed for the number of ATPase-positive Langerhans cells per mm ² after the ATPase staining. For this purpose, an arbitrarily selected range of 3 different people was paid out for each preparation of a subject and the mean value was determined. The results of these histological evaluation are shown in Table I as Langerhans cells per mm ^2. On average, for the completely untreated area of all 10 subjects, a Langerhans cell density of 1073 ± 214 cells per mm ^{2 was obtained} 48 hours after irradiation with 1.5 MED each the Langerhans cell density in the untreated areas returned to 623 ± 210 cells per mm ^2. If the areas were treated twice a day with the cream according to Example 14 or Comparative Example 1 14 days before the irradiation, the mean was 844 + 233 48 hours after the irradiation or 680 ± 157 or Langerhans cells per mm ² detectable (see Table I)

If one looks at the data relative to the untreated situation in% (see Table II), it can be seen that in the case of the untreated situation after the irradiation the number of Langerhans cells per area decreased to approx. 58%. A pretreatment with the cream of the comparative example 1 led to a reduction to approximately 64% of the initial value of Langerhans cells and pretreatment with the cream of Example 14 resulted in a reduction to approximately 78%

The treatment with the cream of comparative example 1 did not lead to a significant reduction in the UV-light-mediated decrease in Langerhans cells (when compared with untreated, irradiated). Pretreatment with the ecto-containing cream according to example 14 significantly reduced the UV-light-mediated decrease in skin standing Langerhans cells (comparison with untreated, irradiated) The use of ectoin or ectoin derivatives in the form of an O / W emulsion according to the invention showed significantly cytoprotective properties with respect to the UV-light-mediated decrease in skin-standing Langerhans cells within the framework of the chosen test conditions Table I

Langerhans cells / mm ²

* Average of 3 individual determinations

Table II

Relative data (Langerhans cells / mm ² ) to untreated (in%)

Example 15

Hydroqel with ectoin

RAW MATERIAL Art. No. INCI% by weight

A

TIMIRONΘSplendid Gold 117474 (1) Cl 77891 (TITANIUM 0.10

DIOXIDE), MICA, SILICA

Carbopol Ultrez 10 (2) CARBOMER 0.40 water, demineralized AQUA (WATER) 67.70

B

RonaCare "T" M ^from Ectoin 130200 (1) ECTOIN 1, 00

Trιs (hydroxymethyl) amιno- 130132 (1) TROMETHAMINE 0.60 methane Germaben II (3) PROPYLENE GLYCOL, 0.20

DIAZOLIDINYL, UREA, METHYL PARABLES, PROPYL PARABLES

Water, demineralized AQUA (WATER) 10.00

C

Lubrajel DV (4) PROPYLENE GLYCOL, 18.00

POLYGLYCERYLMETH ACRYLATE

D (4) PVM / MA COPOLYMER, Lubrajel Oil PROPLYENE

GLYCOL, GLYCERYL POLY- 2.00 METHACRYLATE

manufacturing

The pearlescent pigment was dispersed in the water of phase A and the Carbopol was added with stirring. After complete dissolution, the pre-dissolved phase B was stirred in. Finally, phases C and D were added

Remarks opaque, gold shimmering gel pH value (25 ° C) 6.5

Viscosity 60,000 mPa s (Brookfield RVT, spindle C, 5 rpm, Helipath) at 25 ° C

Bezugsguellen

(1) Merck KGaA

(2) BF Goodrich GmbH

(3) ISP Global Technologies

(4) Guardian

Example 16

After-shave soft cream

RAW MATERIAL Art.No. INCI% by weight

A

Eumulgin BI (1) CETEARETH-12 0.50 Eumulgin B2 (2) CETEARETH-20 0.50 Cutina MD-V (1) GLYCERYL STEARATE 3.00 Cetiol LC (1) COCO-CAPRYLATE 5.00

CAPRATE

Carbopol Ultrez I O (2) CARBOMER 0.30

B

Water, demineralized AQUA (WATER) 66, 10

Glycenn (87% pure) 104091 (3) GLYCERIN 3.00

Ethanol (96% pure) 100971 (3) ALCOHOL 20.00

Menthol, art 105995 (3) MENTHOL 0.30

Tπs (hydroxymethyl) amino 130132 (3) TROMETHAMINE 0.30 methane

RonaCare ™ Ectoιn 130200 ECTOIN 1, 00

manufacturing

Phases A and B were heated separately to 80 ° C. Phase A was added to phase B with stirring, and homogenized and then cooled to room temperature with stirring

Remarks pH value (25 ° C) 7.25

Viscosity (25 ° C) 34,000 mPa-s (Brookfield RVT, spindle C, 5 rpm, Helipath)

Bezugsguellen

(1) Cognis GmbH

(2) BF Goodrich GmbH

(3) Merck KgaA

Example 17

"TM

Evenmg cream with RonaCare Ectoin RAW MATERIAL Art.-No. INCI% by weight

A

TIMIRONΘSplendid Gold 1 17474 (1) Cl 77891 (TITANIUM 2.00

DIOXIDE), MICA, SILICA

Carbopol ETD 2001 (2) CARBOMER 0.50 citric acid q s 102895 (1) CITRIC ACID water, demineralized AQUA (WATER) 40.00

B 1,2-propanediol 107478 (1) PROPLENE GLYCOL 3.00 RoπaCare ™ Ectoin 130200 (1) ECTOIN 1, 00 water, demineralized AQUA (WATER) 28.45 preservative

C

Hostaphat KL 340 N (3) DILAURETH-4 POSPHATE 3.00

Cetyl alcohol 100989 (1) CETYL ALCOHOL 2.00

Liquid paraffin 107162 (1) PARAFFINUM LIQUIDUM 10.00

(MINERAL OIL)

Cetiol V (4) DECYL OLEATE 6.00

D

Pure ethanolamine 108377 (1) TRIETHANOLAMINE 0.35

Water, demineralized AQUA (WATER) 3.50

Perfume Vogue 2309334 (5) PERFUME 0.20

manufacturing

The pearlescent pigment was dispersed in the water of phase A. Possibly acidified with a few drops of citric acid to reduce the viscosity Phase C was stirred into phase A / B, homogenized, neutralized with phase D, homogenized again and cooled with stirring

Remarks pH value (24 ° C) 5.8

Viscosity 33000 mPa s (Brookfield RVT, spindle C, 5 rpm, Helipath), 24 ° C

Example 18

Pre-Solanum soft cream with RonaCare ™ Ectoin

RAW MATERIAL Art.-No. INCI% by weight

A

Paraffin viscous 107160 (1) PARAFFINUM LIQUIDUM 10.00 (MINERAL OIL)

Cetiol S (2) DIOCTYLCYCLOHEXANE 2.50

Isopropyl palmitate (2) ISOPROPYL PALMITATE 6.50 Miglyol 812 N (3) CAPRYLIC / CAPRIC 1, 00 TRIGLYCERIDE Sunflower oil (4) HELIANTHUS ANNUUS 5.00 (SUNFLOWER SEED OIL)

OXYNEX®K liquid 108324 (1) PEG-8, TOCOPHEROL, 0.10 ASCORBYL, PALMITATE, ASCORBIC ACID, CITRIC ACID

B

Carbopol ETD 2001 (5) CARBOMER 0.30

C

Water, demineralized AQUA (WATER) 68.40 RonaCare ™ Ectoin 130200 (1) ECTOIN 1, 00 Sisterna L70-C (6) AQUA (WATER), SUCROSE 5.00 LAURATE, ALCOHOL

Sodium hydroxide solution, 10% 105588 (1) SODIUM HYDROXIDE 0.00 Preservative 0.00

D

Perfume Nikita (7) PERFUME 0.20

manufacturing

Phase B was dispersed in phase A. The pre-dissolved phase C was added with stirring

Phase A / B added, neutralized, homogenized and phase D was added with stirring

Remarks pH value (25 ° C) 5.5-6.5

Viscosity 1 13000 mPa s (Brookfield RVT, spindle C, 10 rpm, Helipath), 25 ° C

Where to Buy

(1) Merck KGaA

(2) Cognis GmbH

(3) Condea Chemie GmbH

(4) Gustav Heess GmbH

(5) BF Goodrich GmbH

(6) Sisterna C V / Dai-Ichi

(7) Dragoco Example 19

Rich night cream with RonaCare ™ Ectoin RAW MATERIAL Art.-No. INCI% by weight

A

Isolan Gl 34 (1) POLYGLYCERYL-4- 1, 00 ISOSTEARATE

Abil EM 90 (1) CETYL DIMETHICONE 2.00 COPOLYOL

Paracera W 80 (2) CERESIN 1, 50 (MICROCRYSTALLINE WAX)

Cutina HR (3) HYDROGENATED CASTOR 0.50 OIL

Cetiol V (3) DECYL OLEATE 10.00 Dragoxat EH (4) OCTYL OCTANOATE 5.00 Miglyol 812 N (5) CAPRYLIC / CAPRIC 10.00 TRIGLYCERIDE

B

Glycenn (87% pure) 104091 (6) GLYCERIN 2.00

Magnesium sulfate 105882 (6) MAGNESIUM SULFATE 1, 00

heptahydrate

RonaCare ™ Ectoin 130200 (6) ECTOIN 1, 00

Water, demineralized AQUA (WATER) 66.00

preservative

C

Perfume (q s)

manufacturing

Phase A and phase B were heated separately to 80 ° C. Phase B was added to phase A with stirring, homogenized and phase C was added at approx. 35 ° C. The mixture was cooled to room temperature with stirring

Remarks Viscosity 6500 mPa s (Brookfield RVT, spindle C, 20 rpm, Helipath), 25 ° C

Bezugsguellen

(1) Th Goldschmidt AG

(2) Parameter

(3) Cognis GmbH (4) Dragoco Gerberding & Co. AG

(5) Condea Chemie GmbH

(6) Merck KGaA

Example 20

Skin care cream with RonaCare ™ Ectoin RAW MATERIAL Art. INCI% by weight

A

Paraffin viscous 107160 (1) PARAFFINUM LIQUIDUM 8.00 (MINERAL OIL)

Tego Care 150 (2) GLYCERYL STEARATE, 10.00 STEARETH-25, CETETH-20, STEARYL ALCOHOL

Lanette 0 (3) CETEARYL ALCOHOL 1, 50

Isopropyl palmitate (3) ISOPROPYL PALMITATE 5.00

Abil Wax 2434 (2) STEAROXY DIMETHICONE 1, 60

Miglyol 812 N (4) CAPRYLIC / CAPRIC 2.00 TRIGLYCERIDE

Dow Coming 200 Fluid (5) DIMETHICONE 0.30

(350 it)

B

Glycerin (87% pure) 104091 (1) GLYCERIN 3.00

RonaCare ™ Ectoin 130200 (6) ECTOIN 1, 00

Water, demineralized AQUA (WATER) 67.60

preservative

Perfume oil (q.s

manufacturing

Phase A was heated to 75 ° C. Phase B was heated to 80 ° C. and was added to phase A with stirring, homogenized and phase C was added at approx. 35 ° C. The mixture was cooled to room temperature with stirring.

Remarks- pH value (25 ° C): 5.1

Viscosity 342000 mPa-s (Brookfield RVT, spindle C, 2.5 rpm, Helipath), at 24 ° C

Reference sources (1) Merck KGaA (2) Th Goldschmidt AG

(3) Cognis GmbH

(4) Condea Chemie GmbH

(5) Dow Corning

Example 21

Refreshing cream with RonaCare ™ Ectoin (W / O)

RAW MATERIAL Art.-No. INCI% by weight

A

Liquid paraffin 107162 (1) PARAFFINUM LIQUIDUM 8.00 (MINERAL OIL)

Arlacel P135 (2) PEG-30 5.50 DIPOLYHYDROXYSTEARATE

Miglyol 812 N (3) CAPRYLIC / CAPRIC 4.00 TRIGLYCERIDE

Arlamol HD (2) ISOHEXADECANE 6.00

B

Water, demineralized AQUA (WATER) 46.00

Glycenn (87% pure) 104091 (1) GLYCERIN 4.00

RonaCare ™ Ectoin 130200 (1) ECTOIN 1, 00

Magnesium sulfate 105882 (1) MAGNESIUM SULFATE 0.50

heptahydrate

preservative

C

Ethanol 96% pure 100971 (1) ALCOHOL 25.00

manufacturing

Phase A and phase B were heated separately to 75 ° C. Phase B was added to phase A with stirring, homogenized and phase C was added at approx. 30 ° C. The mixture was cooled to room temperature with stirring Remarks Viscosity: 41000 mPa s (Brookfield RVT, spindle C, 5 rpm, Helipath), at 24 ° C

Bezugsquellen-

(1) Merck KGaA

(2) Uniqema

(3) Condea Chemie GmbH

Example 22

Nourishing skin cream with RonaCare ™ Ectoin (W / O) RAW MATERIAL Art. INCI% by weight

A

Paraffin viscous 107160 (1) PARAFFINUM LIQUIDUM 10.00 (MINERAL OIL)

Hostacerin WO (2) POLYGLYCERYL-2- 6.00 SESQUIISOSTEARATE, CERA ALBA (BEESWAX), CERA MICROCRISTALLINA (MICROCRYSTALLINE WAX), PARAFFINUM LIQUIDUM (MINERAL OIL), MAGNESIUM STEARATE, ALUMINUM STEARATE

Isopropyl palmitate (3) ISOPROPYL PALMITATE 8.00 Paracera M (4) MICROWAX 3.00 Vaseline (5) PETROLATUM 3.00

B

Water, demineralized (1) AQUA (WATER) 65.00

Glycerin (87% pure) 104091 (1) GLYCERIN 4.00

RonaCare ™ Ectoin 130200 ECTOIN 1, 00

preservative

Production.

Phase A and phase B were heated to 80 ° C. Phase B became phase with stirring

A was given, homogenized and cooled to room temperature with stirring Remarks

Viscosity 220000 mPa s (Brookfield RVT, spindle D, 5 rpm, Helipath), at 24 ° C

Bezugsguellen

(1) Merck KGaA

(2) Claπant GmbH

(3) Cognis GmbH

(4) Paramelt

(5) Schumann Sabol

Example 23

W / O / W-N eight cream with RonaCare ™ Ectoir I

RAW MATERIAL Art.-No. INCI weight

A

Bπj 721 P (1) STEARETH-21 2.00

Bπj 72 d) STEARETH-2 3.00

Arlacel P135 (D PEG-30 1, 50 DIPOLYHYDROXYSTEARATE

Jojobaol (2) BUXUS CHINENSIS (JOJOBA 8.00 OIL)

RonaCare ™ 130180 (3) TOCOPHERYL ACETATE 1, 00

tocopherol

Lanette O (4) CETEARYL ALCOHOL 1, 00

Stearic acid 100671 (3) STEARIC ACID 1, 50

Mirasil CM 5 (5) CYCLOMETHICONE 1, 00

B

Glycenn (87% pure) 104091 (3) GLYCERIN 4.00

preservative

RonaCare ™ Ectoin 130200 ECTOIN 1, 00

Water, demineralized AQUA (WATER) 76.00

Sodium hydroxide solution, 10% 105588 (3) SODIUM HYDROXIDE

manufacturing

Phase A and phase B were heated to 75 ° C. Phase A was slowly homogenized, stirred into phase B, possibly neutralized with sodium hydroxide solution and cooled with stirring Remarks pH value (22 ° C) 5.7

Viscosity 24 ° C 42000 mPa s (Brookfield RVT, spindle C, 5 rpm, Helipath)

Bezugsguellen

(1) Uniqema

(2) Gustav Heess GmbH

(3) Merck KGaA

(4) Cognis GmbH

(5) Rhodia GmbH

Example 24

Sprayable sun protection milk with RonaCare ™ Ectoin RAW MATERIAL Art. INCI% by weight

EUSOLEX® 2292 105382 (D OCTYL 7.50 METHOXYCINNAMATE, BHT

EUSOLEX® 4360 105376 (1) BENZOPHENONE-3 2.50 EUSOLEX® HMS 1 1 1412 (D HOMOSALATE 7.00 Hetester PHA (2) PROPYLENE GLYCOL 5.00 ISOCETETH-3 ACETATE

Volpo S-2 (3) STEARETH-2 0.40 Volpo S-10 (3) STEARETH-10 0.80 Pemulen TR-2 (4) ACRYLATES / C 10-30 ALKYL 0.18 ACRYLATE CROSSPOLYMER

Performa V 825 (5) SYNTHETIC WAX 0.80

Dow Corning 200 (100 es) (6) DIMETHICONE 1, 00

OXYNEX® K liquid 108324 (1) PEG-8, TOCOPHEROL, 0, 10 ASCORBYL PALMITATE, ASCORBIC ACID, CITRIC ACID

B

RonaCare ™ Ectoin 130200 (D ECTOIN 1, 00

Water, demineralized AQUA (WATER) 49.82

preservative

Water, demineralized AQUA (WATER) 20.00 EUSOLEX® 232 105372 (1) PHENYLBENZIMIDAZOLE 1, 00 SULFONIC ACID Propylene glycol, 1, 2- (7) PROPYLENE GLYCOL 2.00 Tπethanolamine ultrapure 108377 (1) TRIETHANOLAMINE 0 90

manufacturing

Phase A and phase B were heated to 80 ° C. Phase B became phase with stirring

A given, neutralized at room temperature with phase C and homogenized

Remarks pH value (21 ° C) 7.0 viscosity wassπg

Where to Buy

(1) Merck KGaA

(2) Paroxite Ltd.

(3) Croda GmbH

(4) BF Goodrich GmbH

(5) New Phase Technologies

(6) Dow Corning

(7) Biesterfeld

Example 25

O / W cream with RonaCare ™ Ectoin

RAW MATERIAL Art.-No. INCI% by weight

A

Tego Care 150 d) GLYCERYL STEARATE, 8.00

STEARETH-25, CETETH-20,

STEARYL ALCOHOL

Lanette 18 (2) STEARYL ALCOHOL 1, 00

Isopropyl palmitate (2) ISOPROPYL PALMITATE 3 00

Jojobaol (3) BUXUS CHINENSIS 7 00

(JOJOBA OIL)

B

RonaCare ™ 130200 (4) ECTOIN 1 00 Glycenn (87% pure) 104091 (4) GLYCERIN 3.00 preservative water demineralized AQUA (WATER) 77.00 manufacturing

Phases A and B were heated to 80 ° C. Phase B was added to phase A with stirring and cold-stirred

Remarks pH value (23 ° C) 5.4

Viscosity (24 ° C) 95000 mPa s (Brookfield RVT, spindle C, 5 rpm, Helipath)

Bezugsguellen

(1) Goldschmidt AG

(2) Cognis GmbH

(3) Gustav Heess GmbH

(4) Merck KGaA

Example 26

O / W moisturizer with RonaCare ™ Ectoin

RAW MATERIAL Art.-No. INCI% by weight

A

RonaCare ™ Ectoin 130200 (1) ECTOIN 1, 00

Glycenn (87% pure) 104091 (1) GLYCERIN 3.00

preservative

Water, demineralized AQUA (WATER) 76.20

B

Sisterna SP30-C (2) SUCROSE DISTEARATE 2.70 Sisterna SP70-C (2) SUCROSE STEARATE 0.90 Cetiol OE (3) DICAPRYLYL ETHER 5.00 Miglyol 812 106175 (1) CAPRYLIC / CAPRIC 2.00 TRIGLYCERIDE

Isopropyipalmitate (3) ISOPROPYL PALMITATE 2.00 Cegesoft C 24 (3) OCTYL PALMITATE 7.00 Carbopol ETD 2001 (4) CARBOMER 0.20

C

Sodium hydroxide solution, 10% 105588 (1) SODIUM HYDROXIDE manufacturing

Phase A was heated to 75 ° C., phase B was well premixed in the cold, then heated to 75 ° C., then phase B was added to phase A with stirring, homogenized, neutralized and cold-stirred

Remarks pH value (22 ° C) 6.5

Viscosity (21 ° C) 109000 mPa s (Brookfield RVT, spindle C, 5 rpm, Helipath)

Where to Buy

(1) Merck KGaA

(2) Sistera C V / Dai-lchi

(3) Cognis GmbH

(4) BF Goodrich GmbH

Claims

claims

1. Use of at least one compound selected from a compound of formula 1 a, 1 b

H

a physiologically acceptable salt thereof or a stereoisomeric form thereof, wherein

R ^{1 is} H or alkyl,

R ² H, COOH, COO-alkyl or CO-NH-R ⁵ ,

R ³ and R ⁴ each independently of one another are H or OH,

n 1, 2 or 3,

R ^{5 is} H, alkyl, an amino acid residue, dipeptide residue or tripeptide residue, and

Alkyl is an alkyl radical having 1 to 4 carbon atoms

mean, for the prophylaxis and / or treatment of UV-induced immunosuppression

Use according to claim 1 for protecting Langerhans cells in the skin

Use according to claim 1 or 2 in the form of a topical composition

Use according to one of Claims 1 to 3, characterized in that at least one compound used according to Claim 1 is present in a topical composition in an amount of 0.0001 to 50% by weight, based on the composition

Use according to one of claims 1 to 4, characterized in that

(S) -1, 4,5,6-tetrahydro-2-methyl-4-pyπmιdιncarbonsaure and / or (S, S) -1, 4,5,6-tetrahydro-5-hydroxy-2-methyl-4- pyπmιdιncarboπsaure be used