DE10238449A1 - Cosmetic and / or dermatological preparation - Google Patents

Abstract

Topical preparations containing 8-hexadecen-1,16-dicarboxylic acid and at least one further active ingredient, selected from the group ursolic acid, agouti peptides, licorice root extract, hydroquinone, green tea extract, arbutin, biotin, mulberry extract (Uvea Ursili), glycyrrhizin, placenta extract , Ascorbylglucoside, Endothelin-Antaginosten from chamomile extract.

Description

The present invention relates to the use of known active ingredients for cosmetic and topical dermatological skin lightening or to prevent skin tanning, in particular the skin tan caused by UV radiation, as well as for lightening the natural Hair color.

In a preferred embodiment The present invention relates to cosmetic and dermatological Preparations for the prophylaxis and treatment of cosmetic or dermatological skin lesions such as. the unwanted Pigmentation, for example local hyper and incorrect pigmentation (e.g. moles, freckles), the inhibition of natural Pigmentation, but also for purely cosmetic brightening, the larger individual skin type in itself adequately pigmented Skin surfaces.

For the pigmentation of the skin is responsible for the melanocytes, which is in the lowest layer of the epidermis, the stratum basale, next to the basal cells as - ever depending on the skin type either isolated or more or less frequently occurring pigment-forming cells can be found. Melanocytes contain as characteristic cell organelles melanosomes, in which the melanin is formed. Among other things, when excited by UV radiation reinforced Melanin formed. This is about the living layers of the epidermis (keratinocytes) ultimately in the horny layer (corneocytes) transports and calls one more or less pronounced brownish to brown-black skin color. Melanin is used as a final stage oxidative process, in which tyrosine is involved of the enzyme tyrosinase via several intermediate stages to the brown to brown-black eumelanins (DHICA and DHI Mclanin) or with the participation of sulfur-containing compounds to the reddish pheomelanin converted. DHICA and DHI melanin are produced via the common intermediate stages Dopaquinone and dopachrome. The latter will, partly with the participation of others Enzymes, either in indole-5,6-quinone carboxylic acid or in indole-5,6-quinone implemented, from which the two eumelanins mentioned arise. The Formation of phaeomelanin runs under other about the intermediates dopaquinone and cysteinyldopa.

Similar as with the pigmentation of the skin are for the hair color (pigmentation of the hair) also responsible for melanin-producing melanocytes. The amount and composition of melanin in the hair is determined The natural Hair color that is genetically determined.

Hyperpigmentation problems Skin have diverse Causes or are side effects of many biological processes, e.g. UV radiation (e.g. freckles, ephelides), genetic disposition, Incorrect pigmentation of the skin during wound healing or scarring or skin aging (e.g. Lentigines seniles).

The melanin synthesizing enzymes usually lie in an inhibited state; by solar, alpha or X-rays this inhibition is removed so that more melanin is formed. Conversely, the formation of melanin e.g. by hydroquinone benzyl ether artificially be inhibited so that such Counteract compounds of pigmentation. In mammals through melanotropin in the melanocytes the production of eumelanins stimulated. Through the agouti signal protein, the synthesis of the whole Melanine throttled and rather that of the Phaeomelanine stimulated by it acts as an antagonist on the MSH receptor (melanocortin receptor 1).

There are active ingredients and preparations known, which counteract skin pigmentation. In practical terms Preparations are essentially used based on hydroquinone, some of which only after several weeks Application show their effect, their excessive use on the other hand, is of concern for toxicological reasons. Also the Inhibition of tyrosinase with substances such as kojic acid, ascorbic acid and azelaic acid and their derivatives is common, but has cosmetic and dermatological disadvantages.

To lighten the hair color mostly strongly pro-oxidative processes applied that make the hair strong damage can. The bleaching of hair with hydrogen peroxide is particularly well known here.

The task was to remedy this problem of the present invention.

8-Hexadecen-1,16-dicarboxylic acid (Dioic acid, CAS number 20701-68-2; provisional INCI name Octadecendioic acid) is a metabolite of yeast cells of the Candida strain. It is characterized by the following structure:

A pure fatty acid serves as the starting substance of vegetable origin. This is converted into the hydroxy fatty acid, which then turns into fatty acid aldehyde and ultimately to dicarboxy acid is oxidized. The yeast cells come from selected mutant strains. The Commercial product has a purity of 95%. 8-Hexadecen-1,16-dicarboxylic acid here as a mixture of the cis and trans isomers, the cis isomer predominating in terms of quantity. Oleic acid can in the product approximately be included in a concentration of 3%.

Ursolic acid is a triterpene Carboxylic acid, which occurs in numerous plants like bearberry leaves, in wax coating of apples, Pears, in fruit bowls of cranberries or blueberries, in spices or Medicinal plants such as rosemary, sage, thyme, marjoram, hawthorn, lemon balm and also in different types of vegetables. It is believed to have anticarcinogenic effects.

The Agouti signal protein was first from Central American rodents (agoutis from the Dasyproctidae, occurs in about 20 species in the forests of Central America) isolated in its murine and human form. WO-97/00892 a skin-lightening effect of these forms.

Licorice is a woody perennial that grows to around 1 to 1.5 meters tall. The plant takes its name from the sweet taste of its roots. The licorice root extract is also called liquorice. Licorice was already used in ancient Egypt as a medicinal plant for diseases of the upper respiratory tract. In India and China, liquorice is traditionally used and cultivated as a medicinal herb with an antispasmodic effect. Licorice has a beneficial effect on the ejection, anti-inflammatory and antispasmodic and is therefore mainly used for coughing and stomach irritation. Studies have also identified a component of licorice root that is considered effective in hepatitis C. The liquorice root extract contains 3-8% glycyrrhizin (ammonium and calcium salts of glycyrrhizic acid (20 β-carboxy-11-oxo-30-norolean-12-en-3β-yl-2-0-β-D-glucopyranuronoxyl-α-D -glucopyranosiduronic acid)), which causes the sweet taste. Glycyrrhizin (C ₄₂ H ₆₂ O _{1 6} ), is about 150 times sweeter than cane sugar and hydrolyzes to the aglycon glycyrrhetic acid (C ₃₀ H ₄₆ O ₄ ) and two molecules of glucuronic acid. Other ingredients are coumarins, flavonoids, various sugars, resins and sterols. Hydroquinone is used as an antioxidant, as a photo developer and as a polymerization inhibitor. In nature it occurs in leaf buds of the pear and in blackberry leaves.

In Japan, green tea has been around for almost two thousand years Tradition. He is attributed a positive effect on health. Due to the gentle processing, this tea variant remains the ingredients carotenoids, caffeine, vitamins A, B2, B12, C and E, secondary Plant substances such as polyphenols, flavonoids, saponins obtained. Drinked regularly supposed to be green tea strengthen the immune system and even protect against cancer. to Topical application can extract green tea be used.

Arbutin comes naturally from bear grapes, Cranberries and blueberries and acts as an antioxidant. chemical it is hydroquinone-β-D-glucopyranoside. It prevents the development of the skin pigment melanin by it blocks the enzyme tyrosinase.

Biotin (D-cis-hexahydro-2-oxothieno [3,4-d] imidazole-4-valeric acid) also known as coenzyme R and acts in the organism in carboxylation reactions With. It is synthesized by the human intestinal flora. It will used to treat seborrheic dermatitis in young children.

Bearberry Arctostaphylos uva-ursi (Whitebeam, cranberry, sandberry, wild boxwood, wolf grape) heard to the heather family and is widespread in Europe and America. The dried, whole or cut leaves had a high content of hydroquinone derivatives: up to 12, occasionally up to 15% phenol glycosides, including in particular arbutin and methylarbutin as well as other hydroquinone derivatives (gallic acid esters of arbutin, free Hydroquinone). They have antibacterial activity against various microorganisms on and become inflammatory Diseases used to prepare tea.

Placental extracts are used for manufacturing cosmetic products used. These are lipoid or water soluble Extracts from animal placents. These extracts (usage conc. 2-5%) have a regenerative influence on aging or through more Previously damaged solar radiation Skin and stimulate hair growth afterwards.

Ascorbyl glucoside is a synthetic ascorbic and can be called the precursor of ascorbic acid. The The active ascorbic acid is released e.g. enzymatic in the cells or biological tissues. It is chemical here about ascorbic acid-2-β-D-glucopyranoside. The glycosylation in the 2-position of the enol function of ascorbic acid leads in the same way like the introduction the phosphate protecting group at this position (ascorbyl phosphate) an increase in stability across from Degradation reactions in. Watery Solution. The corresponding ascorbic acid 3-β-D-glucopyranoside is known and increases the stability of ascorbic acid chemical degradation.

Chamomile extract contains substances that act as endothelin antagonists. Endothelin activated via the endothelin receptor indirectly skin pigmentation by enhancing UV-B induced Skin tanning. In Pigment Cell Res. 10: 218-228, 1997 the depigmenting effect of various endothelin antagonists (e.g. chamomile extract). Nevertheless, this publication failed do not point the way to the present invention.

Water-soluble flavonoids like Alpha Glucosyl Rutin are in JP 08099859 . JP 6321759 described as whitening agents, however, these publications could not point the way to the present invention.

MSH antagonists inhibit the Melanogenesis-promoting Effect of the α-melanocyte Stimulating hormone (α-MSH). Competitive inhibitory peptide derivatives of the active α-MSH sequence (His-Phe-Arg-Trp) are about the specialist Easily accessible peptide synthesis. Other physiological α-MSH antagonists are the products of the Agouti locus (see there) or the γ3-MSH.

Substances are used as pH blockers referred to that the ATP-dependent Block proton pump in melanosomes and thus those for melanogenesis necessary lowering of pH to values of 3-5 prevent (JID 105: 3-7, 1995) Nonetheless, this publication failed do not point the way to the present invention. Such pH blockers are, for example, the compounds 2,4-dinitrophenol and carbonyl cyanide ptrifluoromethoxyphenylhydrazone.

about the use of all these substances in combination with 8-hexadecen-1,16-dicarboxylic acid nothing has become known so far.

It was surprising and for the professional not predicting that topical Preparations containing 8-hexadecen-1,16-dicarboxylic acid and at least one further active ingredient selected from the group ursolic acid, agouti peptides, Licorice root extract, Hydroquinone, green tea extract, Arbutin, biotin, mulberry extract (Uvae Ursü), glycyrrhizin, placenta extract, Ascorbyl glucoside, endothelin antagonists, MSH antagonists, pH blockers remedy the disadvantages of the prior art.

All of these combinations work synergistically in terms of the individual components. Therefore, the amount used of depigmenting agents in depigmenting preparations reduced become. Moreover can be more uniform by combining these substances lighter skin tone can be achieved.

It is particularly preferred if 8-hexadecen-1,16-dicarboxylic acid in a total concentration of 0.001-10% by weight, preferably 0.005-8% by weight, especially 0.05 -5 % By weight, based on the total weight of the preparations, is present.

Furthermore, it is particularly preferred if the further active ingredient in a total concentration of 0.001-3% by weight, preferably 0.005-1 % By weight, in particular 0.01-0.2 % By weight based on the total weight of the preparations is present.

Preparations according to the invention are preferred against unwanted Pigmentation of the skin and / or for the treatment of pigmentation disorders or against unwanted Use pigmentation of the hair and / or to lighten the hair.

It is also advantageous to use 8-hexadecen-1,16-dicarboxylic acid to use in the form of one of their enantiomers.

8-hexadecen-1,16-dicarboxylic acid and at least one further active ingredient specified above, hereinafter as "active ingredient according to the invention" has proven to be extremely effective against unwanted pigmentation, in particular local hyperpigmentation and against UV radiation induced skin tanning, both preventive as well as in the sense of treatment. However, it is also extremely advantageous according to the invention the used according to the invention Active ingredient or cosmetic or topical dermatological preparations with an effective content of active ingredient used according to the invention for cosmetic or dermatological treatment undesirable Skin pigmentation, for example inhomogeneous pigmentation the aging skin, lentigines senile or postinflammatory hyperpigmentation to use.

The skin lightening effect of ascorbyl glucoside is known and is described in EP 478404 described. In contrast to pure ascorbic acid, the glucoside is stable on storage and can therefore be advantageously combined with dioic acid.

The depigmenting effectiveness short oligopeptides (length 4-9 amino acids) the active sequences pos. 42–48 (SMNSLDFSS) and in particular items 83-89 (WRPRTP) of the human agouti signal protein has also been described The peptides as well as effective ones Derivatives of these peptides (exchange of individual amino acids, stabilization by acetylation and amidation) can be easily synthesized or manufacture biotechnologically.

• (1) wobei diesen Oligopeptiden als Homo- bzw. Heteromonomeres eine Struktur Val-Val-Arg-Pro (bzw. WRP) zugrundeliegt,
• (2) oder wobei in den monomeren oder homo- oder heterodimeren oder homo- oder heterotrimeren oder homo- oder heterotetrameren Oligopeptide Strukturen wie vorgenannt vorliegen mit dem Unterschiede, daß der C-Terminus und/oder der N-Terminus um bis zu 5 Aminosäuren ergänzt ist, gemäß der Struktur
  
  wobei Ψ und Ω unabhängig voneinander Aminosäuresequenzen von bis zu 5 Aminosäuren darstellen können,
• (3) oder wobei in monomeren oder homo-/hetero-di-, -tri-, oder tetrameren Oligopeptide oder Proteinen mit einem Molekulargewicht zwischen ca. 0,5 und 100 kDalton unter den Punkten (1) und (2) angegebenen Aminosäuresequenzen als einfach vorliegende oder sich mehrfach wiederholende Strukturmotive auftreten,
• (4) oder wobei die monomeren oder homo-/hetero-di-, -tri-, oder tetrameren Oligopeptide oder Proteine am N-Terminus acyliert sind, gemäß der Struktur
  
  wobei Ψ und Ω unabhängig voneinander Aminosäuresequenzen von bis zu 5 Aminosäuren darstellen können und R einen verzweigten oder unverzweigten, gesättigten oder ungesättigten. Kohlenwasserstoffrest, insbesondere einen Alkylrest mit 1 bis 30 Kohlenstoffatomen darstellen,
• (5) oder wobei die monomeren oder homo-/hetero-di-, -tri-, oder tetrameren Oligopeptide oder Proteine am C-Terminus amidiert sind, gemäß der Struktur
  
  wobei Ψ und Ω unabhängig voneinander Aminosäuresequenzen von bis zu 5 Aminosäuren darstellen können, und wobei R' und R" unabhängig voneinander gewählt werden können aus der Gruppe bestehend aus Wasserstoff und der verzweigten oder unverzweigten, gesättigten oder ungesättigten Kohlenwasserstoffreste, insbesondere der Alkylrest mit 1 bis 30 Kohlenstoffatomen.
• (6) oder wobei die monomeren oder homo-/hetero-di-, -tri-, oder tetrameren Oligopeptide oder Proteine am C-Terminus amidiert und am N-Terminus acyliert sind, gemäß der Struktur
  
  wobei Ψ und Ω unabhängig voneinander Aminosäuresequenzen von bis zu 5 Aminosäuren darstellen können, R einen verzweigten oder unverzweigten, gesättigten oder ungesättigten Kohlenwasserstoffrest, insbesondere einen Alkylrest mit 41 bis 30 Kohlenstoffatomen darstellt, und wobei R' und R" unabhängig voneinander gewählt werden können aus der Gruppe bestehend aus Wasserstoff und der verzweigten oder unverzweigten, gesättigten oder ungesättigten Kohlenwasserstoffreste, insbesondere der Alkylrest mit 1 bis 30 Kohlenstoffatomen.
• (7) oder wobei in monomeren oder homo-(hetero-di-, -tri-, oder tetrameren Oligopeptiden oder Proteinen Aminosäuresequenzen als einfach vorliegende oder sich mehrfach wiederholende Strukturmotive auftreten, gemäß den Strukturen
  
  wobei Ψ eine Einfachbindung oder eine Aminosäurensequenz bis zu 5 Aminosäuren darstellen kann, Ω eine Aminosäurensequenz bis zu 15 Aminosäuren darstellen kann, n eine Zahl von 1 bis 25 darstellt, R einen verzweigten oder unverzweigten, gesättigten oder ungesättigten Kohlenwasserstoffrest, insbesondere einen Alkylrest mit 1 bis 30 Kohlenstoffatomen darstellt, und wobei R' und R" unabhängig voneinander gewählt werden können aus der Gruppe bestehend aus Wasserstoff und der verzweigten oder unverzweigten, gesättigten oder ungesättigten Kohlenwasserstoffreste, insbesondere der Alkylrest mit 1 bis 30 Kohlenstoffatomen.

Advantageous agouti peptides in the sense of the invention are one or more monomeric or homo- or heterodimeric or homo- or heterotrimeric or homo- or heterotetrameric oligopeptides,

• (1) where these oligopeptides as homo- or heteromonomers are based on a Val-Val-Arg-Pro (or WRP) structure,
• (2) or wherein in the monomeric or homo- or heterodimeric or homo- or heterotrimeric or Homo- or heterotetrameric oligopeptide structures as mentioned above exist with the difference that the C-terminus and / or the N-terminus are supplemented by up to 5 amino acids, according to the structure
  
  where Ψ and Ω can independently represent amino acid sequences of up to 5 amino acids,
• (3) or wherein in monomeric or homo- / hetero-di-, -tri-, or tetrameric oligopeptides or proteins with a molecular weight between approx. 0.5 and 100 kDalton under the points (1) and (2) given as amino acid sequences structural motifs that are simply present or that repeat themselves repeatedly occur,
• (4) or wherein the monomeric or homo- / hetero-di-, -tri-, or tetrameric oligopeptides or proteins are acylated at the N-terminus, according to the structure
  
  where Ψ and Ω can independently represent amino acid sequences of up to 5 amino acids and R is a branched or unbranched, saturated or unsaturated. Represent hydrocarbon radical, in particular an alkyl radical having 1 to 30 carbon atoms,
• (5) or wherein the monomeric or homo- / hetero-di-, -tri-, or tetrameric oligopeptides or proteins are amidated at the C-terminus, according to the structure
  
  where Ψ and Ω can independently represent amino acid sequences of up to 5 amino acids, and wherein R 'and R "can be selected independently of one another from the group consisting of hydrogen and the branched or unbranched, saturated or unsaturated hydrocarbon radicals, in particular the alkyl radical with 1 to 30 carbon atoms.
• (6) or where the monomeric or homo- / hetero-di-, -tri-, or tetrameric oligopeptides or proteins are amidated at the C-terminus and acylated at the N-terminus, according to the structure
  
  where Ψ and Ω can independently represent amino acid sequences of up to 5 amino acids, R represents a branched or unbranched, saturated or unsaturated hydrocarbon radical, in particular an alkyl radical having 41 to 30 carbon atoms, and wherein R 'and R "can be selected independently of one another from the Group consisting of hydrogen and the branched or unbranched, saturated or unsaturated hydrocarbon radicals, in particular the alkyl radical having 1 to 30 carbon atoms.
• (7) or where amino acid sequences occur in monomeric or homo- (hetero-di-, -tri-, or tetrameric oligopeptides or proteins) as single or repeated structural motifs, according to the structures
  
  where Ψ can represent a single bond or an amino acid sequence up to 5 amino acids, Ω can represent an amino acid sequence up to 15 amino acids, n represents a number from 1 to 25, R represents a branched or unbranched, saturated or unsaturated hydrocarbon radical, in particular an alkyl radical with 1 to Represents 30 carbon atoms, and where R 'and R "can be selected independently of one another from the group consisting of hydrogen and the branched or unbranched, saturated or unsaturated hydrocarbon radicals, in particular the alkyl radical having 1 to 30 carbon atoms.

• (1) wobei diesen Oligopeptiden als Homo- bzw. Heteromonomeres eine Struktur Val-Val-Arg-Pro (bzw. WRP) zugrundeliegt,
• (2) oder wobei in den monomeren oder homo- oder heterodimeren oder homo- oder heterotrimeren oder homo- oder heterotetrameren Oligopeptide Strukturen wie vorgenannt vorliegen mit dem Unterschiede, daß der C-Terminus und/oder der N-Terminus um bis zu 5 Aminosäuren ergänzt ist, gemäß der Struktur
  
  wobei Ψ und Ω unabhängig voneinander Aminosäuresequenzen von bis zu 5 Aminosäuren darstellen können,
• (3) oder wobei in monomeren oder homo-/hetero-di-, -tri-, oder tetrameren Oligopeptide oder Proteinen mit einem Molekulargewicht zwischen ca. 0,5 und 100 kDalton unter den Punkten (1) und (2) angegebenen Aminosäuresequenzen als einfach vorliegende oder sich mehrfach wiederholende Strukturmotive auftreten,
• (4) oder wobei die monomeren oder homo-/hetero-di-, -tri-, oder tetrameren Oligopeptide oder Proteine am N-Terminus acyliert sind, gemäß der Struktur
  
  wobei Ψ und Ω unabhängig voneinander Aminosäuresequenzen von bis zu 5 Aminosäuren darstellen können und R einen verzweigten oder unverzweigten, gesättigten oder ungesättigten Kohlenwasserstoffrest, insbesondere einen Alkylrest mit 1 bis 30 Kohlenstoffatomen darstellen,
• (5) oder wobei die monomeren oder homo-/hetero-di-, -tri-, oder tetrameren Oligopeptide oder Proteine am C-Terminus amidiert sind, gemäß der Struktur
  
  wobei Ψ und Ω unabhängig voneinander Aminosäuresequenzen von bis zu 5 Aminosäuren darstellen können, und wobei R' und R" unabhängig voneinander gewählt werden können aus der Gruppe bestehend aus Wasserstoff und der verzweigten oder unverzweigten, gesättigten oder ungesättigten Kohlenwasserstoffreste, insbesondere der Alkylrest mit 1 bis 30 Kohlenstoffatomen.
• (6) oder wobei die monomeren oder homo-/hetero-di-, -tri-, oder tetrameren Oligopeptide oder Proteine am C-Terminus amidiert und am N-Terminus acyliert sind, gemäß der Struktur
  
  wobei Ψ und Ω unabhängig voneinander Aminosäuresequenzen von bis zu 5 Aminosäuren darstellen können, R einen verzweigten oder unveizweigten, gesättigten oder ungesättigten Kohlenwasserstoffrest, insbesondere einen Alkylrest mit 4 bis 30 Kohlenstoffatomen darstellt, und wobei R' und R" unabhängig voneinander gewählt werden können aus der Gruppe bestehend aus Wasserstoff und der verzweigten oder unverzweigten, gesättigten oder ungesättigten Kohlenwasserstoffreste, insbesondere der Alkylrest mit 1 bis 30 Kohlenstoffatomen.
• (7) oder wobei in monomeren oder homo-/hetero-di-, -tri-, oder tetrameren Oligopeptiden oder Proteinen Aminosäuresequenzen als einfach vorliegende oder sich mehrfach wiederholende Strukturmotive auftreten, gemäß den Strukturen
  
  wobei Ψ eine Einfachbindung oder eine Aminosäurensequenz bis zu 5 Aminosäuren darstellen kann, Ω eine Aminosäurensequenz bis zu 15 Aminosäuren darstellen kann, n eine Zahl von 1 bis 25 darstellt, R einen verzweigten oder unverzweigten, gesättigten oder ungesättigten Kohlenwasserstoffrest, insbesondere einen Alkylrest mit 1 bis 30 Kohlenstoffatomen darstellt, und wobei R' und R" unabhängig voneinander gewählt werden können aus der Gruppe bestehend aus Wasserstoff und der verzweigten oder unverzweigten, gesättigten oder ungesättigten Kohlenwasserstoffreste, insbesondere der Alkylrest mit 1 bis 30 Kohlenstoffatomen, gegen unerwünschte Pigmentierung der Haut. Die die Peptidsequenz am C- bzw. N-Terminus gewünschtenfalls ergänzenden Aminosäuresequenzen konstituieren sich bevorzugt aus proteinogenen Aminosäuren.

An advantageous embodiment of the agouti peptides according to the invention is also considered to be one or more monomeric or homo- or heterodimeric or homo- or heterotrimeric or homo- or heterotetrameric oligopeptides,

• (1) where these oligopeptides as homo- or heteromonomers are based on a Val-Val-Arg-Pro (or WRP) structure,
• (2) or in the monomeric or homo- or heterodimeric or homo- or heterotrimeric or homo- or heterotetrameric oligopeptide structures as mentioned above with the difference that the C-terminus and / or the N-terminus are supplemented by up to 5 amino acids is, according to the structure
  
  where Ψ and Ω can independently represent amino acid sequences of up to 5 amino acids,
• (3) or wherein in monomeric or homo- / hetero-di-, -tri-, or tetrameric oligopeptides or proteins with a molecular weight between approx. 0.5 and 100 kDalton under the points (1) and (2) given as amino acid sequences structural motifs that are simply present or that repeat themselves repeatedly occur,
• (4) or wherein the monomeric or homo- / hetero-di-, -tri-, or tetrameric oligopeptides or proteins are acylated at the N-terminus, according to the structure
  
  where Ψ and Ω can independently represent amino acid sequences of up to 5 amino acids and R represents a branched or unbranched, saturated or unsaturated hydrocarbon radical, in particular an alkyl radical with 1 to 30 carbon atoms,
• (5) or wherein the monomeric or homo- / hetero-di-, -tri-, or tetrameric oligopeptides or proteins are amidated at the C-terminus, according to the structure
  
  where Ψ and Ω can independently represent amino acid sequences of up to 5 amino acids, and wherein R 'and R "can be selected independently of one another from the group consisting of hydrogen and the branched or unbranched, saturated or unsaturated hydrocarbon radicals, in particular the alkyl radical with 1 to 30 carbon atoms.
• (6) or where the monomeric or homo- / hetero-di-, -tri-, or tetrameric oligopeptides or proteins are amidated at the C-terminus and acylated at the N-terminus, according to the structure
  
  where Ψ and Ω can independently represent amino acid sequences of up to 5 amino acids, R represents a branched or unbranched, saturated or unsaturated hydrocarbon radical, in particular an alkyl radical having 4 to 30 carbon atoms, and wherein R 'and R "can be selected independently of one another from the Group consisting of hydrogen and the branched or unbranched, saturated or unsaturated hydrocarbon radicals, in particular the alkyl radical having 1 to 30 carbon atoms.
• (7) or where amino acid sequences occur in monomeric or homo- / hetero-di-, -tri-, or tetrameric oligopeptides or proteins as single or repeated structural motifs, according to the structures
  
  where Ψ can represent a single bond or an amino acid sequence up to 5 amino acids, Ω can represent an amino acid sequence up to 15 amino acids, n represents a number from 1 to 25, R represents a branched or unbranched, saturated or unsaturated hydrocarbon radical, in particular an alkyl radical with 1 to Represents 30 carbon atoms, and wherein R 'and R "can be selected independently of one another from the group consisting of hydrogen and the branched or unbranched, saturated or unsaturated hydrocarbon radicals, in particular the alkyl radical having 1 to 30 carbon atoms, against unwanted pigmentation of the skin Peptide sequence at the C- or N-terminus, if desired, additional amino acid sequences are preferably composed of proteinogenic amino acids.

Tabelle: Drei- und Einbuchstabencodes für Aminosäuren

Table 1 compares the proteinogenic amino acids with their corresponding three and one letter codes.

Table: Three and one letter codes for amino acids

The L-selenocysteine L-cysteine and L-selenomethionine replace L-methionine. Furthermore can single, several or all positions also by the corresponding D-configured stereoisomers to be replaced.

According to the invention are particularly advantageous for example the oligopeptides Val-Val-Arg-Pro, Val-Val-Arg-Pro-Pro and Val-Val-Arg-Pro-Pro-Pro.

According to the invention particularly advantageous are those acylated at the N-terminus and / or amidated at the C-terminus Products of the oligopeptides Val-Val-Arg-Pro, Val-Val-Arg-Pro-Pro and Val-Val-Arg-Pro-Pro-Pro.

Such acylated ones are preferred Oligopeptides that acylate at the N-terminus with unbranched alkanoyl groups are.

wobei R den Stearoyl oder den Palmitoylrest darstellt.Are particularly preferred

where R represents the stearoyl or the palmitoyl radical.

Amino acid sequences to be used according to the invention or oligopeptides are advantageous according to the usual, for example also automated processes (e.g. via so-called peptide synthesizers) available.

Single peptides can be advantageous, for example using an automatic MilliGen 9050 peptide synthesizer, overlapping Peptides with the help of a multiple peptide synthesizer SMPS 350 (ZINSSER Analytics) by solid phase synthesis (R.B.Merrifield (1966) J.Am.Chem.Soc. 85, 2149) according to the Fmoc / But strategy (E. Atherton, R.C. Sheppard; “Solid Phase Peptide Synthesis: A Practical Approach ", IRL Press, Oxford, England (1989).

Coupling and separation steps can be checked by means of on-line UV monitoring. As Solid phase matrix for For example, free peptides can advantageously be modified with a p-alkoxybenzyl alcohol Polystyrene resin (S.-S. Wang; J. Am. Chem. Soc. 95 (1973), p.1328), for peptide amides the Rink amide resin (H.Rink; Tetrahedron Lett. 28 (1987), p.3787) be used. TBTU (2- (1H-benzotriatol-1-yl) -1,1,3,3-tetramethyluronium tetrafluoroborate) can advantageously be used as coupling reagent. (R.Knorr, A. Trzeciak, W.Bannwarth, D.Gillesen; Tetrahedron Lett. 30 (1989), p. 1927) can be used. Usual coupling times are each 10-30, especially about 20 minutes. At the end of the synthesis, the Peptides, for example with the help of trifluoroacetic acid and if desired Additional substances (e.g. phenol, thioanisole, but also water) from Split resin and at the same time freed of all protective groups.

The reaction solution can, for example by dropping in ice-cold diethyl ether, give a crude product which, if desired, is washed with a suitable washing liquid, for example cold diethyl ether can be cleaned and then lyophilized. The crude peptide is then advantageously purified to a purity of> 98% by preparative reversed-phase high-performance liquid chromatography (RP-HPLC) on a C18 column (250 x 10 mm) using an acetonitrile / 0.05% trifluoroacetic acid / water system ,

Protected by the implementation of the N-Terminal resin-bound Peptides with acid chlorides or acid anhydrides (e.g. palmitoyl chloride or lauryl chloride) in a suitable solvent (e.g. dimethylformamide / N-methylmorpholine) can be acylated at the N-terminus Peptides can be obtained in high yields.

The cosmetic or used according to the invention pharmaceutically acceptable oligopeptides, afterwards, regardless whether a single substance or a mixture of isomers or a mixture different individual substances is present, collectively also “used according to the invention Active ingredient "have proven to be excellent active ingredients against undesirable Pigmentation, especially local hyperpigmentation, namely both preventive as well as in the sense of treatment.

According to the invention, the content of active ingredient used according to the invention in the cosmetic or topical dermatological preparations can be 1 ppb (= 1 part per billion = 10 ^-7 % by weight) - 10% by weight, preferably 10 ppb (= 0.01 ppm = 0) , 01 parts per million = 10 ^-6 % by weight) - 5% by weight, in particular 0.05 ppm-0.1% by weight, based on the total weight of the preparations.

Prophylaxis or cosmetic or dermatological treatment with the one used according to the invention Active ingredient or with the cosmetic or topical dermatological Preparations with an effective content of what is used according to the invention Active ingredient takes place in the usual Way, in such a way that the active ingredient according to the invention or the cosmetic or topical dermatological preparations with an effective content of active ingredient used according to the invention the affected skin is applied. It has turned out surprisingly pointed out that the active ingredient according to the invention the underlying objects of the invention. The active ingredient according to the invention can be advantageous be incorporated into usual cosmetic and dermatological preparations, which are available in different Shapes can exist. So can they e.g. a solution, an emulsion of the water-in-oil type (W / O) or of the oil-in-water type (O / W), or a multiple emulsions, for example of the water-in-oil-in-water (W / O / W) type or oil-in-water-in-oil (O / W / O), a hydrodispersion or lipodispersion, a gel, a solid stick, represent a transdermal therapeutic system or an aerosol.

Emulsions according to the invention in the sense of the present invention, for. B. in the form of a cream, a lotion, a cosmetic milk are advantageous and contain, for example, fats, oils, waxes and / or other fat bodies, as well as water and one or more emulsifiers, as are usually used for such a type of formulation.

It is also possible and beneficial in the sense of the present invention, the active ingredient used according to the invention in aqueous Systems or surfactant preparations for cleaning and care of the skin and insert the hair. This includes shower gels, shampoos but also conditioners, hair care treatments, Hair rinses, Hair tonics, sprays etc.

It is of course known to the person skilled in the art that sophisticated cosmetic compositions mostly not without the usual Auxiliaries and additives are conceivable. These include, for example, consistency givers, fillers, Perfume, dyes, emulsifiers, additional active ingredients such as vitamins or proteins, light stabilizers, stabilizers, insect repellents, Alcohol, water, salts, antimicrobial, proteolytic or keratolytic effective substances etc.

It is also beneficial to use the active ingredient 8-hexadecene-1,16-dicarboxylic acid to use in the form of molecular adducts with cyclodextrins. It is believed that the Cyclodextringerüste thereby as a host molecule and 8-hexadecene-1,16-dicarboxylic acid as a guest molecule act. For the preparation, cyclodextrins are dissolved in water and 8-hexadecen-1,16-dicarboxylic acid is added. The molecular adduct falls then as a solid out and can be the usual Cleaning and preparation steps are subjected. It is known to have cyclodextrin-guest complexes in an appropriate solvent (e.g. water) are in equilibrium between the concrete Guest-cyclodextrin Complex and the dissociated form, being cyclodextrin and guest can be separated to a certain extent. Such balance systems are also advantageous in the sense of the present invention.

Mutatis mutandis apply accordingly Requirements for the formulation of medical preparations.

Medical topical compositions in the sense of the present invention generally contain one or several drugs in effective concentration. The simplicity for the sake of a clean distinction between cosmetic and medical application and corresponding products to the legal Regulations of the Federal Republic of Germany referenced (e.g. cosmetics regulation, Food and Drugs Act).

It is also an advantage the used according to the invention To give active ingredient as an additive to preparations that already other active substances for other purposes included.

Accordingly, cosmetic or topical dermatological compositions within the meaning of the present invention, depending on their structure, can be used, for example, as a skin protection cream, Cleansing milk, sunscreen lotion, nutritional cream, day or night cream, etc. It may be possible and advantageous to use the compositions according to the invention as the basis for pharmaceutical formulations.

It is also beneficial in the sense of the present invention, cosmetic and dermatological preparations to create whose main The purpose of protection from sunlight is not, but it still does Contain the content of other UV protection substances. So z. B. in day creams or makeup products usually UV-A or UV-B filter substances incorporated. Also provide UV protection substances, as well such as antioxidants and, if desired, Preservatives, effective protection of the preparations themselves against spoilage. Favorable are also cosmetic and dermatological preparations that in in the form of a sunscreen.

Accordingly, the preparations contain in the sense of the present invention preferably at least one further UV-A, UV-B and / or broadband filter substance. The wording könnert, although not necessary, possibly one or more organic ones and / or contain inorganic pigments as UV filter substances, which can be in the water and / or oil phase.

The preparations according to the invention can also also advantageous in the form of so-called oil-free cosmetic or dermatological Emulsions are present which have a water phase and at least one liquid at room temperature UV filter substance included as a further phase.

Particularly advantageous at room temperature liquid UV filter substances in the sense of the present invention are homomenthyl salicylate (INCI: Homosalate), 2-ethylhexyl-2-cyano-3,3-diphenylacrylate (INCI: Octocrylene), 2-ethylhexyl-2-hydroxybenzoate (2-ethylhexyl salicylate, octyl salicylate, INCI: octyl salicylate) and esters of cinnamic acid, preferably 4-methoxycinnamic acid (2-ethylhexyl) ester (2-ethylhexyl-4-methoxycinnamate, INCI: octyl methoxycinnamate) and 4-methoxycinnamate (Isopentyl 4-methoxycinnamate, INCI: Isoamyl p-methoxycinnamate).

Preferred inorganic pigments are metal oxides and / or other metal compounds which are sparingly soluble or insoluble in water, in particular oxides of titanium (TiO ₂ ), zinc (ZnO), iron (e.g. Fe ₂ O ₃ ), zirconium (ZrO ₂ ), silicon ( SiO ₂ ), manganese (e.g. MnO), aluminum (Al ₂ O ₃ ), cerium (e.g. Ce ₂ 0,), mixed oxides of the corresponding metals as well as mixtures of such oxides and the sulfate of barium (BaSO ₄ ).

The pigments can be advantageous in the sense of present invention also in the form of commercially available oily or aqueous predispersions come into use. These predispersions can advantageously be used as dispersants and / or solubilizing agents may be added.

The pigments can be advantageous according to the invention superficial treated ("coated") be, for example, a hydrophilic, amphiphilic or hydrophobic Character should be formed or preserved. This surface treatment can be that the Pigments according to known methods with a thin hydrophilic and / or hydrophobic inorganic and / or organic layer be provided. The various surface coatings can be in According to the present invention also contain water.

Inorganic surface coatings in the sense of the present invention can consist of aluminum oxide (Al ₂ O ₃ ), aluminum hydroxide Al (OH) ₃ , or aluminum oxide hydrate (also: alumina, CAS no .: 1333-84-2), sodium hexametaphosphate (NaPO ₃ ) ₆ , sodium metaphosphate (NaPO ₃ ) _n , silicon dioxide (SiO ₂ ) (also: silica, CAS No .: 7631-86-9), or iron oxide (Fe ₂ O ₃ ). These inorganic surface coatings can occur alone, in combination and / or in combination with organic coating materials.

Organic surface coatings in the sense of the present invention consist of vegetable or animal aluminum stearate, vegetable or animal stearic acid, Lauric acid, Dimethylpolysiloxane (also: Dimethicone), methylpolysiloxane (Methicone), Simethicone (a mixture of dimethylpolysiloxane with an average chain length from 200 to 350 dimethylsiloxane units and silica gel) or alginic acid. This organic surface coatings can alone, in combination and / or in combination with inorganic Coating materials occur.

Geeignete Titandioxidpartikel und Vordispersionen von Titandioxidpartikeln sind unter folgenden Handelsbezeichnungen bei den aufgeführten Firmen erhältlich:

Vorteilhafte UV-A-Filtersubstanzen im Sinne der vorliegenden Erfindung sind Dibenzoylmethanderivate, insbesondere das 4-(tert.-Butyl)-4'-methoxydibenzoylmethan (CAS-Nr. 70356-09-1 ), welches von Givaudan unter der Marke Parsol^® 1789 und von Merck unter der Handelsbezeichnung Eusolex^® 9020 verkauft wird.Zinc oxide particles and predispersions of zinc oxide particles suitable according to the invention are available under the following trade names from the listed companies:

Suitable titanium dioxide particles and predispersions of titanium dioxide particles are available under the following trade names from the companies listed:

Advantageous UV-A filter substances for the purposes of the present invention are dibenzoylmethane derivatives, in particular 4- (tert-butyl) -4'-methoxydibenzoylmethane (CAS-Nr. 70356-09-1), marketed by Givaudan under the trade name Parsol ^® 1789 and is sold by Merck under the trade name Eusolex ^® 9020.

• – Phenylen-l,4-bis-(2-benzimidazyl)-3,3'-5,5'-tetrasulfonsäure und ihre Salze, besonders die entsprechenden Natrium-, Kalium- oder Triethanolammonium-Salze, insbesondere das Phenylen-1,4-bis-(2-benzimidazyl)-3,3'-5,5'-tetrasulfonsäure-bis-natriumsalz mit der INCI-Bezeichnung Bisimidazylate (CAS-Nr.: 180898-37-7), welches beispielsweise unter der Handelsbezeichnung Neo Heliopan AP bei Haarmann & Reimer erhältlich ist;
• – Salze der 2-Phenylbenzimidazol-5-sulfonsäure, wie ihr Natrium-, Kalium- oder ihr Triethanolammonium-Salz sowie die Sulfonsäure selbst mit der INCI Bezeichnung Phenylbenzimidazole Sulfonsäure (CAS.-Nr. 27503-81-7), welches beispielsweise unter der Handelsbezeichnung Eusolex 232 bei Merck oder unter Neo Heliopan Hydro bei Haarmann & Reimer erhältlich ist;
• – 1,4-di(2-oxo-10-Sulfo-3-bornylidenmethyl)-Benzol (auch: 3,3'-(1,4-Phenylendimethylene)bis-(7,7-dimethyl-2-oxo-bicyclo-(2.2.1]hept-1-ylmethan Sulfonsäure) und dessen Salze (besonders die entprechenden 10-Sulfato-verbindungen, insbesondere das entsprechende Natrium-, Kalium- oder Triethanolammonium-Salz), das auch als Benzol-1,4-di(2-oxo-3-bornylidenmethyl-10-sulfonsäure) bezeichnet wird. Benzol-1,4-di(2-oxo-3-bornylidenmethyl-10-sulfonsäure) hat die INCI-Bezeichnung Terephtalidene Dicampher Sulfonsäure (CAS.-Nr.: 90457-82-2) und ist beispielsweise unter dem Handelsnamen Mexoryl SX von der Fa. Chimex erhältlich;
• – Sulfonsäure-Derivate des 3-Benzylidencamphers, wie z. B. 4-(2-Oxo-3-bornylidenmethyl)benzolsulfonsäure, 2-Methyl-5-(2-oxo-3-bornylidenmethyl)sulfonsäure und deren Salze.

Advantageous further UV filter substances in the sense of the present invention are sulfonated, water-soluble UV filters, such as. B .:

• - Phenylene-1,4-bis (2-benzimidazyl) -3,3'-5,5'-tetrasulfonic acid and its salts, especially the corresponding sodium, potassium or triethanolammonium salts, in particular phenylene-1,4 -bis- (2-benzimidazyl) -3,3'-5,5'-tetrasulfonic acid bis-sodium salt with the INCI name bisimidazylate (CAS no .: 180898-37-7), which, for example, under the trade name Neo Heliopan AP is available from Haarmann &Reimer;
• - Salts of 2-phenylbenzimidazole-5-sulfonic acid, such as its sodium, potassium or triethanolammonium salt and the sulfonic acid itself with the INCI name phenylbenzimidazole sulfonic acid (CAS No. 27503-81-7), which, for example, under the Trade name Eusolex 232 is available from Merck or under Neo Heliopan Hydro from Haarmann &Reimer;
• - 1,4-di (2-oxo-10-sulfo-3-bornylidenemethyl) benzene (also: 3,3 '- (1,4-phenylenedimethylene) bis- (7,7-dimethyl-2-oxobicyclo - (2.2.1] hept-1-ylmethane sulfonic acid) and its salts (especially the corresponding 10-sulfato compounds, especially the corresponding sodium, potassium or triethanolammonium salt), which is also called benzene-1,4-di (2-oxo-3-bornylidenemethyl-10-sulfonic acid) Benzene-1,4-di (2-oxo-3-bornylidenemethyl-10-sulfonic acid) has the INCI name Terephtalidene Dicampher Sulfonic Acid (CAS no. : 90457-82-2) and is available, for example, under the trade name Mexoryl SX from Chimex;
• - Sulfonic acid derivatives of 3-benzylidene camphor, such as. B. 4- (2-oxo-3-bornylidene methyl) benzenesulfonic acid, 2-methyl-5- (2-oxo-3-bornylidene methyl) sulfonic acid and salts thereof.

Advantageous UV filter substances In the sense of the present invention, so-called broadband filters are also i.e. Filter substances that contain both UV-A and UV-B radiation absorb.

• – 2,4-Bis-{[4-(2-Ethyl-hexyloxy)-2-hydroxy]-phenyl}-6-(4-methoxyphenyl)-1,3,5-triazin (INCI: Aniso Triazin), welches unter der Handelsbezeichnung Tinosorb^® S bei der CIBA-Chemikalien GmbH erhäliaich ist;
• – Diethylhexylbutylamidotriazon (INCI: Diethylhexylbutamidotriazone), welches unter der Handelsbezeichnung UVASORB HEB bei Sigma 3V erhältlich ist;
• – 4,4',4"-(1,3,5-Triazin-2,4,6-triyltrümino)-tris-benzoesäure-tris(2-ethylhexylester), auch: 2,4,6-Tris-[anilino-(p-carbo-2'-ethyl-1'-hexyloxy)]-1,3,5-triazin (INCI: Ethylhexyl Triazone), welches von der BASF Aktiengesellschaft unter der Warenbezeichnung UVINUL^® T 150 vertrieben wird.

Advantageous broadband filters or UV-B filter substances are, for example, triazine derivatives, such as, for. B.

• - 2,4-bis - {[4- (2-ethylhexyloxy) -2-hydroxy] phenyl} -6- (4-methoxyphenyl) -1,3,5-triazine (INCI: Aniso triazine), which is available from CIBA-Chemicals GmbH under the trade name Tinosorb ^® S;
• - Diethylhexylbutylamidotriazon (INCI: Diethylhexylbutamidotriazone), which is available under the trade name UVASORB HEB from Sigma 3V;
• - 4,4 ', 4 "- (1,3,5-triazine-2,4,6-triyltrümino) tris-benzoic acid tris (2-ethylhexyl ester), also: 2,4,6-tris [anilino - (p-carbo-2'-ethyl-1'-hexyloxy)] - 1,3,5-triazine (INCI: Ethylhexyl Triazone), which is sold by BASF Aktiengesellschaft under the trade name UVINUL ^® T 150.

An advantageous broadband filter in the sense of the present invention is also the 2,2'-methylenebis (6- (2H-benzotriazol-2-yl) -4- (1,1,3,3-tetramethylbutyl) phenol), which under the trade name Tinosorb ^® M is available from CIBA-Chemicals GmbH.

Another advantageous broadband filter for the purposes of the present invention is 2- (2H-benzotriazol-2-yl) -4-methyl-6- [2-methyl-3- [1,3,3,3-tetramethyl-1 - [( trimethylsilyl) oxy] disiloxanyl] propyl] phenol (CAS No .: 155633-54-8) with the INCI name Drometrizole Trisiloxane, which is available under the trade name Mexoryl ^® XL from Chimex.

The other UV filter substances can be oil soluble or water soluble his.

• – 3-Benzylidencampher-Derivate, vorzugsweise 3-(4-Methylbenzyliden)campher, 3-Benzylidencampher;
• – 4-Aminobenzoesäure-Derivate, vorzugsweise 4-(Dimethylamino)-benzoesäure(2-ethylhexyl)ester, 4-(Dimethylamino)benzoesäureamylester;
• – Derivate des Benzophenons, vorzugsweise 2-Hydroxy-4-methoxybenzophenon, 2-Hydroxy-4-methoxy-4'-methyibenzophenon, 2,2'-Dihydroxy-4-methoxybenzophenon
• – sowie an Polymere gebundene UV-Filter.
• – 3-(4-(2,2-bis Ethoxycarbonylvinyl)-phenoxy)propenyl)-methoxysiloxan/Dimethylsiloxan-Copolymer welches beispielsweise unter der Handelsbezeichnung Parsol® SLX bei Hoffmann La Roche erhältlich ist.

Advantageous oil-soluble UV-B and / or broadband filter substances in the sense of the present invention are e.g. B .:

• - 3-benzylidene camphor derivatives, preferably 3- (4-methylbenzylidene) camphor, 3-benzylidene camphor;
• - 4-aminobenzoic acid derivatives, preferably 4- (dimethylamino) benzoic acid (2-ethylhexyl) ester, 4- (dimethylamino) benzoic acid amyl ester;
• - Derivatives of benzophenone, preferably 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxy-4'-methyibenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone
• - As well as UV filters bound to polymers.
• - 3- (4- (2,2-bis-ethoxycarbonylvinyl) phenoxy) propenyl) methoxysiloxane / dimethylsiloxane copolymer which is available, for example, from Hoffmann La Roche under the trade name Parsol® SLX.

Advantageous water-soluble filter substances are e.g. B .:
Sulfonic acid derivatives of 3-benzylidene camphor, such as. B. 4- (2-oxo-3-bornylidene methyl) benzenesulfonic acid, 2-methyl-5- (2-oxo-3-bornylidene methyl) sulfonic acid and salts thereof.

A further light protection filter substance according to the invention to be used advantageously is ethylhexyl-2-cyano-3,3-diphenylacrylate, obtainable (octocrylene) from BASF under the name Uvinul ^® N 539th

Particularly advantageous preparations in the sense of the present invention, which is characterized by a high or very high UV-A and / or UV-B protection in addition to the filter substance or substances according to the invention) furthermore preferably further UV-A and / or broadband filters, in particular Dibenzoylmethane derivatives [for example the 4- (tert-butyl) -4'-methoxydibenzoylmethane], Phenylene-1,4-bis (2-benzimidazyl) -3,3'-5,5'-tetrasulfonic acid and / or their salts, the 1,4-di (2-oxo-10-sulfo-3-bornylidenemethyl) benzene and / or its salts and / or the 2,4-bis - {[4- (2-ethylhexyloxy) -2-hydroxyj-phenyl} -6- (4-methoxyphenyl) -1,3,5-triazine, respectively individually or in any combination with each other.

The list of UV filters mentioned, which can be used within the meaning of the present invention Of course not be limiting.

The preparations according to the invention advantageously contain the substances that UV radiation in the UV-A and / or UV-B range absorb, in a total amount of e.g. B. 0.1% by weight to 30% by weight, preferably 0.5 to 20% by weight, in particular 1.0 to 15.0% by weight, in each case based on the total weight of the preparations, for cosmetic Preparations available to place the hair or skin in front of the entire area protect from ultraviolet radiation.

The cosmetic and dermatological invention Preparations can cosmetic active, auxiliary and / or contain additives, as is usually the case in such preparations be used, e.g. Antioxidants, preservatives, Bactericides, particles, Anti-foaming agents, dyes, pigments, the coloring Have an effect, thickeners, surface-active substances, emulsifiers, softening, moisturizing and / or moisturizing substances, Fats, oils, waxes or other usual Components of a cosmetic or dermatological formulation such as alcohols, polyols, polymers, foam stabilizers, electrolytes, organic solvents or silicone derivatives.

It is also beneficial to Preparations for the purposes of the present invention are customary antioxidants inflict. According to the invention as favorable Antioxidants all for cosmetic and / or dermatological applications suitable or common Antioxidants are used.

The antioxidants are advantageously chosen from the group consisting of amino acids (eg glycine, histidine, tyrosine, tryptophan) and their derivatives, imidazoles (eg urocanic acid) and their derivatives, peptides such as D, L-carnosine, D-carnosine, L-carnosine and their derivatives (e.g. anserine), carotenoids, carotenes (e.g. α-carotene, β-carotene, lycopene) and their derivatives, retinoids such as retinol, retinal and / or retinoic acid and the respective esters, α-lipoic acid and their derivatives ( e.g. dihydroliponic acid), aurothioglucose, propylthiouracil and other thiols (e.g. thioredoxin, glutathione, cysteine, cystine, cystamine and their glycosyl, N-acetyl, methyl, ethyl, propyl, amyl, butyl and lauryl, palmitoyl -, Oleyl, γ-linoleyl, cholesteryl and glycene esters) and their salts, dilauryl thiodipropionate, distearyl thiodipropionate, thiodipropionic acid and their derivatives (esters, ethers, peptides, lipids, nucleotides, nucleosides and salts) as well as sulfoximine compounds (e.g. buthioninsulfoximine e, homocysteine sulfoximine, buthionine sulfones, penta-, hexa-, heptathionine sulfoximine) in very low tolerable doses (e.g. pmol to μmol / kg), also (metal) chelators (e.g. α-hydroxy fatty acids, palmitic acid, phytic acid, lactoferrin), α-hydroxy acids (e.g. citric acid, lactic acid, malic acid), humic acid, bile acid, bile extracts, bilirubin, biliverdin, EDTA, EGTA and their derivatives, unsaturated fatty acids and their derivatives (e.g. γ-linolenic acid, linoleic acid, oleic acid), folic acid and its derivatives, -2- Aminopropionic acid diacetic acid, flavonoids, polyphenols, catechins, ubiquinone and ubiquinol and their derivatives, vitamin C and derivatives (e.g. ascorbyl palmitate, Mg ascorbyl phosphate, ascorbylacetate), tocopherols and derivatives (e.g. vitamin E acetate), as well as coniferylbenzate and the benzoic acid benzoate of rutin Derivatives, ferulic acid and its derivatives, butylated hydroxytoluene, butylated hydroxyanisole, nordihydroguajakh resin acid, nordihydroguajaretic acid, trihydroxybutyrophen on, uric acid and its derivatives, mannose and its derivatives, zinc and its derivatives (e.g. ZnO, ZnSO ₄ ) selenium and its derivatives (e.g. selenium methionine), stilbenes and their derivatives (e.g. stilbene oxide, trans-stilbene oxide) and the derivatives suitable according to the invention ( Salts, esters, ethers, sugars, nucleotides, nucleosides, peptides and lipids) of these active ingredients.

The amount of antioxidants (a or more compounds) in the preparations is preferably 0.001 to 30% by weight, particularly preferably 0.05-20% by weight, in particular 0.1-10% by weight, based on the total weight of the preparation.

If vitamin E and / or its Derivatives that are antioxidants are advantageous their respective concentrations in the range of 0.001-10% by weight, based on the total weight of the formulation.

• – Wasser oder wäßrige Lösungen
• – Öle, wie Triglyceride der Caprin- oder der Caprylsäure, vorzugsweise aber Rizinusöl;
• – Fette, Wachse und andere natürliche und synthetische Fettkörper, vorzugsweise Ester von Fettsäuren mit Alkoholen niedriger C-Zahl, z.B. mit Isopropanol, Propylenglykol oder Glycerin, oder Ester von Fettalkoholen mit Alkansäuren niedriger C-Zahl oder mit Fettsäuren;
• – Alkohole, Diole oder Polyole niedriger C-Zahl, sowie deren Ether, vorzugsweise Ethanol, Isopropanol, Propylenglykol, Glycerin, Ethylenglykol, Ethylenglykolmonoethyl- oder -monobutylether, Propylenglykolmonomethyl, -monoethyl- oder- monobutylether, Diethylenglykolmonomethyl- oder -monoethylether und analoge Produkte.

If the cosmetic or dermatological preparation in the sense of the present invention is a solution or emulsion or dispersion, the following can be used as solvents:

• - water or aqueous solutions
• - oils, such as triglycerides of capric or caprylic acid, but preferably castor oil;
• - Fats, waxes and other natural and synthetic fat bodies, preferably esters of fatty acids with alcohols with a low C number, for example with isopropanol, propylene glycol or glycerol, or esters of fatty alcohols with alkanoic acids with a low C number or with fatty acids;
• - 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 glycol monomethyl or monoethyl ether and similar products.

In particular, mixtures of the aforementioned solvents used. With alcoholic solvents water can be another ingredient.

The oil phase of the emulsions, oleogels or hydrodispersions or lipodispersions in the sense of the present Invention is advantageously chosen from the group of esters from saturated and / or unsaturated, branched and / or unbranched alkane carboxylic acids with a chain length of 3 to 30 carbon atoms and saturated and / or unsaturated, branched and / or unbranched alcohols with a chain length of 3 to 30 carbon atoms, from the group of esters from aromatic carboxylic acids and saturated and / or unsaturated, branched and / or unbranched alcohols with a chain length of 3 to 30 carbon atoms. Such ester oils can then advantageously chosen are selected from the group of 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-hexyldecyl stearate, 2-octyldodecyl palmitate, oleyl oleate, olerlerucate, Erucyl oleate, erucylerucate as well as synthetic, semi-synthetic and natural Mixtures of such esters, e.g. Jojoba oil.

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

Any mix of such oil and wax components are to be used advantageously for the purposes of the present invention. It may also be advantageous to use waxes, for example Cetyl palmitate, to be used as the sole lipid component of the oil phase.

Advantageously, the oil phase selected from the group 2-ethylhexyl isostearate, octyldodecanol, isotridecyl isononanoate, isoeicosane, 2-ethylhexyl cocoate, C _12-15 alkyl benzoate, caprylic-capric acid triglyceride, dicaprylyl ether.

Particularly advantageous are mixtures of C _12-15 -alkyl benzoate and 2-ethylhexyl isostearate, mixtures of C _12-15 -alkyl benzoate and isotridecyl isononanoate and mixtures of C _12-15 -alkyl benzoate, 2-ethylhexyl isostearate and isotridecyl isononanoate.

Of the hydrocarbons are Paraffin oil, Squalane and squalene advantageous for the purposes of the present invention to use.

The oil phase can also be advantageous have a content of cyclic or linear silicone oils or completely such oils exist, although it is preferred, except the silicone oil or silicone oils one additional Content of other oil phase components to use.

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

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

Gels used according to the invention usually contain Low C number alcohols, e.g. Ethanol, isopropanol, 1,2-propanediol, Glycerin and water or an oil mentioned above in the presence a thickener, which is preferred for oily-alcoholic gels Silicon dioxide or an aluminum silicate, in the case of aqueous alcoholic or alcoholic Gel is preferably a polyacrylate.

Fixed pens contain e.g. natural or synthetic waxes, fatty alcohols or fatty acid esters. To be favoured Lip care pens and pen formulations for body deodorization used.

usual Basic materials for the use as cosmetic pencils in the sense of the present Are suitable, liquid oils (e.g. Paraffin oils, castor oil, Isopropyl myristate), semi-solid components (e.g. petroleum jelly, lanolin), solid components (e.g. beeswax, ceresin and microcrystalline Waxes or ozokerite) as well as high-melting waxes (e.g. carnauba wax, Candelilla).

As a propellant for cosmetic sprayable from aerosol containers and / or dermatological preparations within the meaning of the present Invention are the usual known volatile, liquefied propellant, for example hydrocarbons (propane, butane, isobutane) are suitable, which can be used alone or in a mixture with one another. Also Compressed air is advantageous to use.

Of course, the specialist knows that it is there are non-toxic propellants that are essential for the realization of the present Invention in the form of aerosol preparations would be suitable to which, however, because of harmful effects on the environment or other circumstances should be avoided, especially fluorocarbons and Chlorofluorocarbons (CFCs).

Cosmetic preparations in the sense of the present invention also present as gels, in addition to an effective content of the active ingredient according to the invention and usually for that solvents used, preferably water, still organic thickeners, e.g. gum arabic, Xanthan gum, sodium alginate, cellulose derivatives, preferably methyl cellulose, Hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, Hydroxypropylmethyl cellulose or inorganic thickeners, z. B. aluminum silicates such as bentonite, or a mixture from polyethylene glycol and polyethylene glycol stearate or distearate, contain. The thickener is in the gel e.g. in a lot between 0.1 and 30% by weight, preferably between 0.5 and 15% by weight, contain.

Preparations according to the invention, the hair cosmetic Cleaning preparations for representing the hair or scalp can be in liquid or solid form. They preferably contain at least one anionic, non-ionic or amphoteric surfactants Substance or mixtures thereof, optionally an electrolyte and tools as they are usually used for that become. The surface active Substance can be in a concentration between 1 and 94 wt .-% in the cleaning preparations are present, based on the total weight of the preparations, but in particular between 1 and 50% by weight.

In particular, aqueous cosmetic Detergent or for aqueous cleaning certain low-water or water-free detergent concentrates contain anionic, nonionic and / or amphoteric surfactants, for example conventional ones Soaps, e.g. fatty acid salts of sodium, alkyl sulfates, alkyl ether sulfates, alkane and alkyl benzene sulfonates, Sulfoacetates, sulfobetaines, sarcosinates, amidosulfobetaines, sulfosuccinates, Sulfobernsteinsäurehalbesfer, Alkyl ether carboxylates, protein fatty acid condensates, Alkyl betaines and amido betaines, fatty acid alkanolamides, polyglycol ether derivatives contain.

Anionic surfactants are preferably used in concentrations between 5% and 20% by weight. Sodium Laureth sulfates such as Texapon N 70 from the Henkel or Disodium Laureth Sulfosuccinate as it is offered under the name Rewopol SBFA 30 by Witco. Nonionic surfactants are preferably used in concentrations of 1% by weight to 10% by weight. Examples are decyl glucoside as it is offered by the company Seppic under the name Oramix NS 10 or polysorbate 80 as it is offered by the company ICI under the name Tween 80. Amphoteric surfactants are preferably used in concentrations of 1% by weight to 10% by weight. Examples are cocamidopropyl betaine as it is offered as Tego betaine by the company Goldschmidt or sodium cocoamphoacetate as it is offered under the name Miranol Ultra by the company Rhone Poulenc.

The percentages refer on the total weight of the preparations.

Furthermore, in the hair cosmetic Detergent conditioning aids may be included, e.g. in Quantities from 0.001 to 10 wt .-%, based on the total weight of the Preparations. The preferred conditioning aids include polymers quaternary Connections (quats). Polymer quats are often used in shampoos e.g. used with a concentration of 0.01 to 2 wt .-%. To belong Polyquaternium-10 as it is called Polymer JR 400 from offered by Amerchol or hydroxypropyl guar Hydroxypropyltrimonium Chloride as it is called Jaguar C 162 is offered by the company Rhone-Poulenc.

The preparations according to the invention can be cosmetic Contain auxiliaries as they are usually used used in such preparations, e.g. Preservatives, perfumes, Anti-foaming agents, foam stabilizers, Dyes, pigments that have a coloring Have an effect, thickeners, surface-active substances, emulsifiers, softening, moisturizing and / or moisturizing substances, moisturizing Agents, fats, oils, Waxes, alcohols, polyols and their toxicologically acceptable Ethers and esters, branched and / or unbranched hydrocarbons, other antioxidants, stabilizers, pH regulators, consistency enhancers, Bactericides, deodorants, antimicrobials, antistatic agents, UV absorbers, complexing and sequestering agents, pearlescent agents, Polymers, electrolytes, organic solvents, silicone derivatives, Plant extracts, vitamins and / or other active ingredients or other common ingredients a cosmetic or dermatological formulation. Even solution brokers, e.g. for incorporating hydrophobic components such as of perfume preparations can be included.

The total amount of auxiliary substances is, for example 0.001 to 15 wt .-%, preferably 0.01 to 10 wt .-%, each based on the total weight of the preparation.

The water content of the preparations is for example 50 to 95% by weight, preferably 55 to 90% by weight, each based on the total weight of the preparation.

The pH of the preparations can adjusted in a known manner by adding acids or bases preferably by adding buffer mixtures, e.g. on Base of citric acid / citrate or phosphoric acid Phosphate buffer mixtures. The pH is preferably below 10, e.g. in the range of 4-8, especially in the 5-7 range.

Particularly advantageous preparations are also obtained when antioxidants as additives or active ingredients be used. Included according to the invention the preparations advantageously one or more antioxidants. As cheap, but still optional antioxidants can all for cosmetic and / or dermatological applications suitable or customary Antioxidants are used.

It is also advantageous to add antioxidants to the preparations according to the invention. The antioxidants are advantageously selected from the group consisting of amino acids (eg glycine, histidine, tyrosine, tryptophan) and their derivatives, imidazoles (eg urocanic acid) and their derivatives, peptides such as D, L-carnosine, D-carnosine, L-carnosine and their derivatives (e.g. anserine), carotenoids, carotenes (e.g. α-carotene, β-carotene, 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, 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 their derivatives (esters, ethers, peptides, lipids, nucleotides, nucleosides and salts) as well as sulfoximine compounds (e.g. buthioninsulfoximines, homocysteine sulfoximine, buthioninsulfones, penta-, hexa-, H eptathioninsulfoximine) in very low tolerable doses (e.g. pmol to μmol / kg), also (metal) chelators (e.g. α-hydroxy fatty acids, palmitic acid, phytic acid, lactoferrin), α-hydroxy acids (e.g. citric acid, lactic acid, malic acid), humic acid, bile acid , Biliary extracts, bilirubin, biliverdin, EDTA, EGTA and their derivatives, unsaturated fatty acids and their derivatives (e.g. γ-linolenic acid, linoleic acid, oleic acid), folic acid and their derivatives, ubiquinone and ubiquinol and their derivatives, vitamin C and derivatives (e.g. ascorbyl palmitate, Mg ascorbyl phosphate, ascorbyl acetate), tocopherols and derivatives (e.g. vitamin E acetate), vitamin A and derivatives (vitamin A palmitate) as well as coniferyl benzoate of benzoin, rutinic acid and its derivatives, a-glycosyl rutin, ferulic acid, furfurylidene glucitol, carnosine Butylated hydroxytoluene, butylated hydroxyanisole, nordihydroguajakarzarzäure, Nordihydroguajaretsäure, trihydroxybutyrophenon, uric acid and their Derivatives, mannose and their derivatives, zinc and its derivatives (e.g. ZnO, ZnSO ₄ ) selenium and its derivatives (e.g. selenomethionine), stilbenes and their derivatives (e.g. stilbene oxide, trans-stilbene oxide) and the derivatives suitable according to the invention (salts, esters, ethers , Sugars, nucleotides, nucleosides, peptides and lipids) of these active ingredients.

Particularly advantageous in the sense of The present invention can use oil-soluble antioxidants be used.

An amazing property of the The present invention is that preparations according to the invention are very good vehicle for are cosmetic or dermatological active ingredients in the skin, whereby preferred active ingredients are antioxidants which protect the skin from being oxidative Protect stress can. Preferred antioxidants are vitamin E and its derivatives and vitamin A and its derivatives.

The amount of antioxidants (a or more compounds) in the preparations is preferably 0.001 to 30% by weight, particularly preferably 0.05-20% by weight, in particular 1-10% by weight, based on the total weight of the preparation.

If vitamin E and / or its Derivatives that are antioxidants are advantageous their respective concentrations in the range of 0.001-10% by weight, based on the total weight of the formulation.

If vitamin A or vitamin A derivatives, or carotenes or their derivatives represent the antioxidant (s), is advantageous, their respective concentrations from the range from 0.001-10 % By weight, based on the total weight of the formulation.

The following examples are intended clarify the present invention.

All quantities, percentages or parts, unless otherwise stated, refer to the Total weight of the preparations or the respective mixtures.

As a licorice root extract, it became an oil-soluble one Licorice root extract, available used by Maruzen Pharmaceuticals Ltd. This draws with a particularly pronounced synergistic effect with 8-hexadecen-1,16-dicarboxylic acid out.

Examples

Beispiele 1–10: O/W-Cremes

Beispiel 11: W/O-Creme

Beispiel 12: Hydrodispersion/Gelcreme

Beispielrezepturen Foundations

Beispielrezepturen Mikroemulsionen

Beispiele Pickering

Beispiele W/O Stifte

Beispielrezepturen Foundations

Examples 1-10: O / W creams

Example 11: W / O cream

Example 12: Hydrodispersion / Gel Cream

Sample recipes foundations

Sample formulations of microemulsions

Examples Pickering

Examples W / O pens

Sample recipes foundations

Claims (5)

Topical preparations containing 8-hexadecen-1,16-dicarboxylic acid and at least one further active ingredient selected from the group ursolic acid, agouti peptides, Licorice root extract, Hydroquinone, green tea extract, Arbutin, biotin, mulberry extract (Uvae Ursii), glycyrrhizin, placenta extract, Ascorbyl glucosides, endothelin antagonists from chamomile extract. Preparations according to claim 1, characterized in that 8-hexadecen-1,16-dicarboxylic acid in one Total concentration 0.001-10 % By weight, preferably 0.005-8 % By weight, in particular 0.05-5 % By weight, based on the total weight of the preparations, is present. Preparations according to claim 1, characterized in that the further Active ingredient in a total concentration of 0.001-3% by weight, preferably 0.005-1% by weight, especially 0.01-0.2 % By weight, based on the total weight of the preparations, is present. Use of preparations according to at least one of claims 1 to 2 against unwanted pigmentation the skin and / or to treat pigmentation disorders. Use of preparations according to at least one of claims 1 and 2 against unwanted pigmentation of the hair and / or for lightening the hair.