WO2012163469A2 - Extracts from eugenia uniflora - Google Patents

Abstract

The present invention relates to the use of extracts of parts of the plant Eugenia uniflora for lightening the skin, and also to cosmetic preparations comprising these extracts, and to a process for producing such preparations.

Description

 Extracts from Eugenia uniflora

The present invention relates to the use of extracts of plant parts of Eugenia uniflora for lightening the skin, and to cosmetic preparations containing these extracts and to a process for the preparation of such preparations.

Skin and hair color are dependent on the content, size, distribution and type of the nitrogen-containing, dark dye melanin, which is produced in the melanocyte-capable cells (melanocytes).

 Starting with tyrosine and using various melanocyte-specific enzymes, e.g. Tyrosinase or tyrosinase-related proteins, melanin is synthesized within the melanocytes.

Subsequently, the melanin is transferred to the keratinocytes in the form of so-called melanosomes. Although the melanin in the skin one

In addition to providing suitable protection against UV radiation, darker or over-pigmented skin can affect beauty and lead to serious aesthetic problems. Hyperpigmented areas of skin or lesions contain melasma (also called chloasma), i. irregularly shaped yellowish-brown spots.

In general, one differentiates between pigment spots between freckles (ephelides), age spots (lentigines), so-called age warts

(Verrucae seborrhoicea) and hyperpigmentation (e.g., Chloasma or Melasma). Freckles are especially prone to skin type I, i. with very light skin and reddish hair.

Hyperpigmentation (chloasma), on the other hand, is common in those women who routinely deliver estrogen to their bodies. Very often the sun plays an important role. You can prevent it especially by regular sunscreen with a high SPF. In order to remove unsightly pigment spots, different ones are available

Options such as laser, dermabrasion or other electrosurgical Procedures and so-called bleaching creams. The latter alternative has the advantage that it is much cheaper for the patient than the electrosurgical procedures. In addition, the application is easier and more enjoyable.

A large number of skin-whitening compounds for the treatment of pigmentation marks are available on the market. Among others, these are compounds such as e.g. Hydroquinone (1,4-dihydroxybenzene), kojic acid, arbutin, aloesin, niacinamide, vitamin C or rucinol, which suppress the production of melanin in the skin. Also

 Plant extracts such as e.g. from Morus alba or Phyllanthus emblica find, especially in the Southeast Asian region, application to brighten the Hautteint.

 This can be done using different mechanisms.

However, most of the skin lightening agents delay the conversion of tyrosine into melanin by blocking the enzyme tyrosinase. However, these known compounds have a number of disadvantages, such as e.g. low depigmentation efficiency, side effects such as skin irritation or skin exfoliation, cell damage, low

Skin penetration or low durability or stability of

 Formulations. Therefore, a need for new safe

 Skin whitening with higher effectiveness and good

Formulation properties available. The invention has for its object to overcome the disadvantages indicated in the prior art and to develop effective alternatives that have an effective ability to brighten the skin - with the aim of improving the cosmetic effectiveness while reducing the side effects. Surprisingly, it has now been found that extracts from

Plant parts of Eugenia uniflora have a high skin lightening effect. Eugenia uniflora is a shrub with edible fruits that lives in the

 Gardening is commercially available. Extracts of the leaves are used as fragrances due to their content of essential oils.

Extracts of Eugenia uniflora have a skin lightening effect is not known in the prior art.

JP 05-155750 A describes the use of extracts of Eugenia jambolana for skin lightening. Based on this document, however, the use of Eugenia un / / ora extracts for skin lightening is not suggested, since species of the same genus do not necessarily contain the same ingredients and therefore not the same

Have to show effect. For example, Eugenia jambolana contains Eugenin (Segupta et al., 1965, Journal of the Indian Chemical Society 42: 255-258), which is known for its inhibiting effect of melanin synthesis (JP 05-301813 A), therefore, the skin-lightening activity of Eugenia jambolana can be explained by the presence of Eugenin. In contrast, this substance could not be detected in Eugenia uniflora extracts (see Example 3), which is why the skin lightening effect of extracts from Eugenia uniflora is particularly surprising.

A first object of the present invention is therefore the

Use of an extract of plant parts of Eugenia uniflora for lightening the skin.

According to the extracts of Eugenia uniflora plant parts with good compatibility at the same time have valuable cosmetic and / or pharmacological properties in that the lightening of the skin is associated with a relative melanin content of less than 90%, preferably less than 80%, particularly preferably less than 70%. A preferred embodiment of the present invention is the

Use of an extract from plant parts of Eugenia uniflora for the inhibition of tyrosinase. The inhibition of tyrosinase can also be done in vitro. The term "inhibition" refers to any reduction in activity that is based on the action of the specific extract of the invention and is made possible by recognition, binding and blocking of the target molecules.

The aforementioned use of the extract can be done in in vitro or in vivo models. The susceptibility of a particular cell to treatment with the extract can be determined by testing in vitro. Typically, a culture of the cell with the

Extract of the invention is incubated at various concentrations for a period of time sufficient to allow the active agents to inhibit the synthesis of melanin, usually between about one hour and one week. For testing in vitro cultured

Cells from a biopsy sample can be used. The amount of post-treatment melanin in the cells is then determined. The use in vitro is carried out in particular on samples of

Mammalian species that suffer from skin pigmentation disorders. The host or patient may be of any mammalian species, e.g. B. one

 Primate species, especially humans, but also rodents

(including mice, rats and hamsters), rabbits, horses, cattle, dogs, cats, etc. The in vivo dose of the extract is beneficial to the susceptibility of the

Tyrosinase and / or severity of the pigmentation disorder of the patient matched with regard to the in vitro data, which significantly increases the effectiveness is. Typically, a cosmetic dose will be sufficient to significantly reduce the undesirable amount of melanin in the target tissue while maintaining and ultimately improving the patient's quality of life.

Use will generally continue until there is a significant reduction in tyrosinase activity and melanin production, e.g. at least about 10% reduction in melanin content and can be continued until essentially no undesirable

Overproduction of melanin is more demonstrated. It is understood that a skin lightening a repeated or lasting

Treatment, since after discontinuation of the preparations, the normal

Melaninsyntheserate is resumed. Another preferred embodiment of the present invention is the use of an extract from plant parts of Eugenia uniflora for the prophylaxis, treatment and / or follow-up of pigmentary disorders of the skin. According to the invention, extracts from Eugenia uniflora plant parts are suitable for use in the prophylaxis, treatment and / or follow-up of pigment disorders selected from the group of hyperpigmentation, freckles, age spots and sunspots. The use of the extracts from plant parts of Eugenia uniflora can therefore be more cosmetic or pharmaceutical, in particular

dermatological, being nature. It is preferably a

cosmetic use, more preferably a non-therapeutic cosmetic use. In principle, all above-ground parts of the plant can be used for the extract, for example the leaves, flowers or fruits. Preferred plant parts are the leaves. The plant extract from Eugenia uniflora can be prepared by methods known to those skilled in the art. A plant extract which is particularly suitable for the use according to the invention is prepared as follows:

a) Extraction of plant parts of Eugenia uniflora by means of a

Solvent and

b) removing the solvent.

The plant parts can be used directly for the extraction according to step a). Typically, however, the plant parts are first dried and crushed.

 The drying can be carried out, for example, in air or preferably in a vacuum drying oven at elevated temperature, preferably between 30 and 50 ° C., more preferably at about 40 ° C.

The crushing can be done by a common method, for example with the help of cutting tools such as knives or scissors, or with the help of a

Mixing device done.

Subsequently, the plant parts are extracted. The extraction is carried out by methods known to those skilled in the art. For this, the plant parts are mixed with a solvent.

Preference is given to using a solvent selected from water, organic solvents or mixtures thereof. Examples of organic solvents are methanol, ethanol, 1-propanol, 2-propanol, acetonitrile, acetone or ethyl acetate. Solvent mixtures of water and organic solvents preferably contain 10-90% by volume of water, more preferably 30-70% by volume of water.

 In a preferred embodiment of the present invention, the solvent is selected from water or alcohol, preferably ethanol. In a particularly preferred embodiment, water is used as

Solvent used.

The extraction is typically carried out at temperatures between 20 and 90 ° C, preferably between 50 and 90 ° C, more preferably at 70 ° C.

In step b) the solvent is removed. This is typically done by filtration.

Optionally, the extract obtained can then be concentrated and / or dried in a step c).

This can be done using methods common to the person skilled in the art. The

Concentration takes place, for example, using a

Rotary evaporator or a falling film evaporator, and can also be done under reduced pressure. The drying of the extract can

for example by means of spray-drying or freeze-drying. Preferably, the extract is complete to constant weight

dried.

It is believed that the high skin whitening activity of

extracts according to the invention, without being bound to this theory, is due to a combination of different active components in the extracts. The skin-lightening effect of the extract is particularly good when it is prepared by the method described above and in particular according to its preferred embodiments. A further embodiment of the present invention relates to the above-described use of extracts of plant parts of Eugenia uniflora in combination with at least one further active ingredient, preferably from the group of antioxidants, vitamins, UV filters, skin lightening agents, self-tanning agents, anti-inflammatory agents, antimicrobial drugs

skin moisturizing agents, anti-aging agents and anti-cellulite agents is selected. Preferably, the use is in combination with at least one or more UV filters or at least one further active substance or extract with a skin-lightening activity.

Another object of the present invention is a preparation containing an extract of plant parts of Eugenia uniflora and one or more UV filters.

Likewise provided by the present invention is a preparation comprising an extract of Eugenia uniflora and at least one further active substance or extract having a skin-lightening activity.

For the purposes of the present invention, the term "preparation" is synonymous with the term "agent", "composition" or "formulation" used. The preparations are usually topically applicable preparations, e.g. cosmetic or dermatological formulations or medical devices. Topically applicable means according to the invention that the preparation externally and locally

is applied, i. that the preparation must be suitable, for example, to be applied to the skin can. The preparations in this case contain a cosmetic, pharmaceutical or

dermatologically suitable carrier and as desired Property profile optional further suitable ingredients. The topical preparations are preferably used as a cosmetic or dermatological preparation, particularly preferably as a cosmetic

Preparation.

The preparations may comprise or contain, consist essentially of or consist of the necessary and optional ingredients mentioned above and / or below. All connections or

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

The preparations according to the invention preferably contain from 0.01 to 99% by weight of the extract from Eugenia uniflora, based on the total weight of the preparation. Preferably, an amount of 0.05 to 30 wt.% Is used, particularly preferably from 0, 1 to 10 wt.%. The expert does not have any difficulties in selecting the quantities according to the intended effect of the preparation. In principle, all UV filters can be used in the preparations according to the invention. Particularly preferred are those UV filters whose physiological harmlessness has already been demonstrated. Both for UVA and UVB filters, there are many known and proven substances from the literature. The compounds listed in the following lists are to be considered as examples only. Of course, other UV filters can be used.

Preferred formulations may contain organic UV filters, so-called hydrophilic or lipophilic sunscreen filters, which are in the UVA range and / or UVB range and / or IR and / or VIS range

(Absorber) are effective. These substances can be synthesized in particular under p-aminobenzoic acid derivatives, salicylic acid derivatives, β, β-diphenyl acrylate derivatives. derivatives, triazine derivatives, cinnamic acid derivatives and polymeric filters and silicone filters described in application WO 93/04665. Further examples of organic filters are given in the patent application EP-A 0 487 404. In the following, the named UV filters are usually named according to the INCI nomenclature.

Particularly suitable for a combination are: para-aminobenzoic acid and its derivatives: PABA, ethyl PABA, ethyl dihydroxypropyl PABA, ethylhexyl dimethyl PABA, e.g. sold under the name "Escalol 507" by the company ISP, glyceryl PABA, PEG-25 PABA, e.g. sold under the name "Uvinul P25" from BASF.

Salicylates: homosalates sold under the name "Eusolex HMS" by Merck; Ethyl hexyl salicylates, e.g. sold under the name "Neo Heliopan OS" by Symrise; Dipropylene glycol salicylates, e.g.

sold under the name "Dipsal" by the company Scher; TEA salicylates, e.g. sold under the name "Neo Heliopan TS" by Fa. Symrise. β, β-diphenylacrylate derivatives: octocrylenes, e.g. distributed under the

Name "Eusolex® OCR" from Merck, "Uvinul N539" from BASF, etocrylene, for example sold under the name "Uvinul N35" from BASF, Benzophenone derivatives: benzophenone-1, for example sold under the name "Uvinul 400"; benzophenone-2, for example sold under the name "Uvinul D50"; benzophenone-3 or oxybenzone, for example sold under the name "Uvinul M40"; benzophenone-4, for example sold under the name "Uvinul MS40"; benzophenone -9, for example sold under the name "Uvinul DS-49" from BASF, benzophenone-5, benzophenone-6, for example sold under the name "Helisorb 11" by Norquay, benzophenone-8, for example

sold under the name "Spectra-Sorb UV-24" from American Cyanamid; Benzophenone-12 n-hexyl 2- (4-diethylamino-2-hydroxybenzoyl) benzoate or 2-hydroxy-4-methoxybenzophenone, sold by Merck, Darmstadt, under the name Eusolex® 4360. Benzylidene camphor derivatives: 3-benzylidene camphor, for example sold under the name "Mexoryl SD" from the company. Chimex; 4-Methylbenzyliden- camphor, for example sold under the name "Eusolex 6300" from the company. Merck; Benzylidencamphorsulfonsäure, eg sold under the name "Mexoryl SL" from the company. Chimex; Camphor benzalkonium methosulfate, for example sold under the name "Mexoryl SO" from the company. Chimex;

 Terephthalylidenedicamphorosulfonic acid, e.g. sold under the name "Mexoryl SX" by Chimex; Polyacrylamidomethylbenzylidene camphor, sold under the name "Mexoryl SW" from Chimex. Phenylbenzimidazole derivatives: phenylbenzimidazole sulfonic acid, e.g.

sold under the name "Eusolex 232" by Merck; Disodium phenyl dibenzimidazole tetrasulfonate, e.g. sold under the name "Neo Heliopan AP" by Symrise. Phenylbenzotriazole derivatives: Drometrizol trisiloxanes, e.g. sold under the name "Silatrizole" by the company Rhodia Chimie; Methylenebis (benzotriazolyl) tetramethylbutylphenol in solid form, e.g. sold under the name "MIXXIM BB / 100" from Fairmount Chemical, or in micronized form as an aqueous dispersion, e.g. sold under the name "Tinosorb M" from BASF.

Triazine derivatives: ethylhexyltriazone, e.g. sold under the name "Uvinul T150" from BASF; Diethylhexylbutamidotriazone, e.g.

marketed under the name "Uvasorb HEB" by the company Sigma 3V; 2,4,6-tris (diisobutyl 4'-aminobenzalmalonate) -s-triazines or 2,4,6-tris (biphenyl) -1,3,5-triazines, sold as Tinosorb A2B by BASF; 2,2 '- [6- (4-methoxyphenyl) -1, 3,5-triazine-2,4-diyl] bis [5- (2-ethylhexyl) oxy] phenol, sold as Tinosorb S from BASF; N2, N4-bis [4- [5- (1, 1-dimethylpropyl) -2-benzoxazolyl] phenyl] -N6- (2-ethylhexyl) -1, 3,5-triazine-2,4,6-triamine, sold as Uvasorb K 2A from Sigma 3V,

Bis (butylbenzoate) diaminotriazine aminopropyltrisiloxane (Mexoryl SBS).

Anthraniline derivatives: menthyl anthranilate, e.g. distributed under the

Name "Neo Heliopan MA" from the company Symrise.

Imidazole derivatives: Ethylhexyldimethoxybenzylidenedioxoimidazoline propionate.

Benzalmalonate Derivatives: Polyorganosiloxanes containing functional benzalmalonate groups, e.g. Polysilicone-15, e.g. sold under the name "Parsol SLX" by Hoffmann LaRoche.

4,4-Diarylbutadiene derivatives: 1,1-dicarboxy (2,2'-dimethylpropyl) -4,4-diphenylbutadiene.

Benzoxazole Derivatives: 2,4-bis [5- (1-dimethylpropyl) benzoxazol-2-yl (4-phenyl) imino] -6- (2-ethylhexyl) imino-1,3,5-triazines, e.g. distributed under the

Names Uvasorb K2A from the company Sigma 3V and mixtures containing this.

Piperazine derivatives such as the compound

or the UV filters of the following structures

It is also possible to use UV filters based on polysiloxane copolymers having a random distribution according to the following formula, where e.g. a = 1 2; b = 58 and c = 2.8 are:

 Suitable organic UV-protective substances are preferably to be selected from the following list: ethylhexyl salicylate,

Phenylbenzimidazole sulfonic acid, benzophenone-3, benzophenone-4, benzophenone-5, n-hexyl 2- (4-diethylamino-2-hydroxybenzoyl) benzoate, 4-methylbenzylidene camphor, terephthalylidenedicamphor sulfonic acid, disodium phenyldibenzimidazole tetrasulfonate,

Methylenebis (benzotriazolyl) tetramethylbutylphenol, ethylhexyltriazone, diethylhexylbutamidotriazone, drometrizole trisiloxane, polysilicone-15,1,1-dicarboxy (2,2'-dimethylpropyl) -4,4-diphenylbutadiene, 2,4-bis [5-1 (Dimethylpropyl) -benzoxazol-2-yl (4-phenyl) imino] -6- (2-ethylhexyl) imino-1,3,5-triazines and mixtures thereof.

These organic UV filters are incorporated usually in an amount of 0.01 to 20 weight percent, preferably 1 to 20 wt .-%, in formulations.

The preparations may contain, in addition to the extract and the optionally organic UV filters, as described above, further inorganic UV filters, so-called particulate UV filters. These combinations with particulate UV filters are possible both as a powder and as a dispersion or paste of the following types.

In this case, both those from the group of titanium dioxides, such as.

coated titanium dioxide (for example Eusolex ^® T-2000, Eusolex ^® T-AQUA, Eusolex ^® T-AVO, Eusolex ^® T-OLEO), zinc oxides (for example Sachtotec® ^®),

Iron oxides or else cerium oxides and / or zirconium oxides are preferred.

Furthermore, combinations with pigmentary Titandixoxid or zinc oxide are possible, wherein the particle size of these pigments is greater than or equal to 200 nm, for example ^® Hombitan FG or Hombitan ^® FF Pharma.

It may further be preferred if the preparations contain inorganic UV filters which are prepared by customary methods, such as, for example, in US Pat

Cosmetics & Toiletries 1990, 105, 53 have been post-treated. This may include one or more of the following

 Aftertreatment components are selected: amino acids, beeswax, fatty acids, fatty acid alcohols, anionic surfactants, lecithin,

Phospholipids, sodium, potassium, zinc, iron or aluminum salts of fatty acids, polyethylenes, silicones, proteins (especially collagen or Elastin), alkanolamines, silica, alumina, other metal oxides, phosphates, such as sodium hexametaphosphate or glycerol.

Preferably used particulate UV filters are:

untreated titanium dioxides, e.g. the products Microtitanium Dioxide MT 500 B from Tayca; Titanium Dioxide P25 from Degussa,

 Post-treated micronized titanium dioxides with alumina and

 Silica post-treatment such as e.g. the product "Microtitanium Dioxide MT 100 SA of Tayca; or the product "Tioveil Fin" from Uniqema,

 Aftertreated micronised titanium dioxides with alumina and / or aluminum stearates / laurate aftertreatment such as e.g. Microtitanium Dioxide MT 100 T from Tayca, Eusolex T-2000 from Merck,

Post-treated micronized titanium dioxides with iron oxide and / or

 Iron stearates aftertreatment such as e.g. the product "Microtitanium

Dioxide MT 100 F "from Tayca,

 Aftertreated micronised titanium dioxides with silicas,

 Alumina and silicone aftertreatment such as e.g. the product "Microtitanium Dioxide MT 100 SAS", the company Tayca,

- Post-treated micronized titanium dioxides with

 Sodium hexameta-phosphates, e.g. the product "Microtitanium

 Dioxide MT 150 W "from the company Tayca.

The treated micronized titanium dioxides used for combination may also be post-treated with:

 - octyltrimethoxysilanes; such as. the product Tego Sun T 805 of the Fa.

 Degussa,

 - silica; such as. the product Parsol T-X from DSM,

 Alumina and stearic acid; such as. the product UV-Titan M160 of the company Sachtleben,

 - aluminum and glycerin; such as. the product UV titanium of the Fa.

Sachtleben Aluminum and silicone oils, such as, for example, the product UV titanium M262 from Sachtleben,

 Sodium hexamethaphosphate and polyvinylpyrrolidone,

 Polydimethylsiloxanes, e.g. the product 70250 Cardre UF Ti02SI3 "from the company Cardre,

 Polydimethylhydrogensiloxanes, e.g. the product Microtitanium

 Dioxide USP Grade Hydrophobia "from Color Techniques.

Furthermore, the combination with the following products may also be advantageous:

- Untreated zinc oxides such. B. the product Z-Cote Fa. BASF

 (Sunsmart), Nanox of the company Elementis

 Aftertreated zinc oxides such as the following products:

 • "Zinc Oxide CS-5" from Toshibi (ZnO aftertreated with

 polymethylhydrogenosiloxane)

 • Nanogard Zinc Oxide FN from Nanophase Technologies

• "SPD-Z1" from Shin-Etsu (ZnO aftertreated with a

 Silicone-grafted acrylic polymer dispersed in cyclodimethylsiloxanes

 "Escalol Z100" from ISP (alumina aftertreated ZnO dispersed in an ethylhexyl methoxycinnamate / PVP-hexadecenes / methicone copolymer blend)

 Fuji ZNO-SMS-10 from Fuji Pigment (ZnO aftertreated with silica and polymethylsilsquioxane);

 Untreated cerium oxide micropigment e.g. with the name "Colloidal Cerium Oxide" from Rhone Poulenc

 • Untreated and / or post-treated iron oxides with the

 Name Nanogar of the Fa. Arnaud.

By way of example, it is also possible to use mixtures of different metal oxides, for example titanium dioxide and cerium oxide with and without after-treatment, such as, for example, the product Sunveil A from Ikeda. Besides, too Mixtures of alumina, silica and silicone aftertreated titanium dioxide / zinc oxide mixtures, such as the product UV titanium M261 Fa. Sachtleben be used. These inorganic UV filters are incorporated usually in an amount of 0.1 to 25 weight percent, preferably 2 to 10 wt .-%, in the preparations.

By combining one or more of the compounds mentioned with UV filter action, the protective effect against harmful

Effects of UV radiation can be optimized.

All mentioned UV filters can also be used in encapsulated form. In particular, it is beneficial to use organic UV filters in

to use encapsulated form. The capsules are in

Preparations to be used according to the invention are preferably contained in amounts which ensure that the encapsulated UV filters are present in the above-mentioned weight percent ratios in the preparation.

Skin-lightening active ingredients (or synonymously depigmenting agents) which can be used in the preparations according to the invention can, in principle, be all active ingredients known to the person skilled in the art. Commercially available melanogenesis inhibitors such as ascorbic acid and its derivatives, aloesin, niacinamide, emblica, elagic acid, licorice extract, mulberry tree extract, kojic acid, licorice root extract, rucinol, hydroquinone, azelaic acid, arbutin, magnesium ascorbyl phosphate or the like are suitable for combination. Preferred examples of compounds having skin-lightening activity are hydroquinone, niacinamide, ascorbic acid and physiologically acceptable salts thereof, kojic acid, arbutin, aloesin, azelaic acid, elagic acid or rucinol. Preferred examples of extracts with skin-lightening activity are licorice extract, mulberry extract or emblica.

Furthermore, at least one further active ingredient can be present in the preparations according to the invention. The further active ingredient is preferably selected from the group of UV filters, antioxidants, vitamins, skin-lightening agents, anti-aging agents, anti-inflammatory agents, antimicrobial agents, agents for improving the moisture content of the skin (skin moistness regulators), anti-cellulite agents, Anti-wrinkle agents, anti-dandruff agents, anti-acne agents, deodorants, pigments and

Self-tanning substances, more preferably from the group of UV filters, antioxidants, vitamins, skin lightening agents, self-tanning substances, anti-aging agents and anti-cellulite agents, most preferably from the group of UV filters, antioxidants, vitamins and skin lightening agents ,

In a preferred embodiment of the invention, the

Preparation of at least one substance which serves to maintain and / or improve the moisture content of the skin.

 These substances may, without being construed as limiting, include, among others, substances belonging to the so-called natural moisturizing factors, e.g. 2-oxopyrrolidines 5-carboxylic acid.

In a further preferred embodiment of the invention, the preparation contains one or more antioxidants and / or one or more vitamins. Through the use of antioxidants, a protective effect against oxidative stress or against the action of radicals can generally be achieved, whereby the expert has no difficulty in selecting suitable fast or delayed-acting antioxidants. There are many well-known and proven from the literature Substances that can be used as antioxidants, eg

Amino acids (e.g., glycine, histidine, tyrosine, tryptophan) and theirs

Derivatives, imidazoles, (e.g., urocaninic acid) and derivatives thereof, peptides, e.g. D, L-carnosine, D-carnosine, L-carnosine and their derivatives (e.g.

Anserine), carotenoids, carotenes (such as α-carotene, β-carotene, lycopene) and their derivatives, chlorogenic acid and its derivatives, lipoic acid and its derivatives (such as dihydrolipoic acid), aurothioglucose, propylthiouracil and other thiols (such as 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 its derivatives (such as esters, ethers, peptides, lipids, nucleotides, nucleosides and salts) as well as sulfoximine compounds (such as buthionine sulfoximines,

Homocysteine sulfoximine, buthionine sulfone, penta-, hexa-,

Heptathioninsulfoximin) in very low tolerated dosages (such as pmol to μηΓΐοΙ / kg), (metal) chelators, (such as a-hydroxy fatty acids, palmitic acid, phytic acid, lactoferrin), α-hydroxy acids (such as citric acid, lactic acid, Malic acid), humic acid, bile acid, bile extracts, bilirubin, biliverdin, EDTA, EGTA, pentasodium

ethylenediaminetetramethylene phosphonate and its derivatives, unsaturated fatty acids and their derivatives, vitamin C and derivatives (e.g.

Ascorbyl palmitate, magnesium ascorbyl phosphate, ascorbyl acetate),

Tocopherols and derivatives (such as vitamin E acetate), vitamin A and derivatives (such as vitamin A palmitate), and coniferyl benzoate of the

Benzoin, rutinic acid and its derivatives, α-glycosyl rutin,

Ferulic acid, furfurylidene glucitol, carnosine, butylhydroxytoluene,

Butylated hydroxyanisole, Nordohydroguajaretsäure, Trihydroxybutyrophenon, Quercitin, uric acid and its derivatives, mannose and its derivatives, zinc and its derivatives (such as ZnO, ZnS0 ₄ ), selenium and its derivatives (such as selenomethionine), silibens and their derivatives (such as Stilbene oxide, trans-stilbene oxide). Further suitable antioxidants are also described in WO 2006/111233 and WO 2006/111234.

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

 wherein

R ¹ -C (O) CH ₃ , -CO ₂ R ³ , -C (O) NH ₂ and -C (O) N (R ⁴ ) ₂ ,

 X is O or NH,

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

R ^{3 is} linear or branched alkyl having 1 to 20 C atoms,

R ^{4 are} each independently H or linear or branched

Alkyl having 1 to 8 C atoms,

R ⁵ H, linear or branched alkyl having 1 to 8 carbon atoms or

 linear or branched alkoxy having 1 to 8 C atoms and

R ^{6 is} linear or branched alkyl having 1 to 8 carbon atoms.

Preference is given to derivatives of 2- (4-hydroxy-3,5-dimethoxybenzylidene) malonic acid and / or 2- (4-hydroxy-3,5-dimethoxybenzyl) -malonic acid, more preferably 2- (4-hydroxy-3,5 -dimethoxybenzylidene) -malonic acid bis (2-ethylhexyl) esters (eg Oxynex® ST Liquid) and / or 2- (4-hydroxy-3,5-dimethoxybenzyl) -malonic acid bis (2-ethylhexyl) esters (eg RonaCare® AP).

Mixtures of antioxidants are also suitable for use in the formulations of the invention. Known and commercially available mixtures are, for example, mixtures containing as active Ingredients lecithin, L - (+) - ascorbyl palmitate and citric acid, natural tocopherols, L - (+) - ascorbyl palmitate, L - (+) - ascorbic acid and

Citric acid (such as Oxynex ^® K LIQUID), tocopherol extracts from natural sources, L - (+) - ascorbyl palmitate, L - (+) - ascorbic acid and citric acid (such as Oxynex L LIQUID ^®), DL-a-tocopherol, L- ( +) - ascorbyl palmitate, citric acid and lecithin (such as Oxynex ^® LM) or butylhydroxytoluene (BHT), L - (+) - ascorbyl palmitate and citric acid (such as Oxynex ^® 2004). Such antioxidants are used with compounds of formula (I) or sub-formulas thereof in such compositions usually in weight percent ratios in the range of 1000: 1 to 1: 1000, preferably in weight percent ratios of 100: 1 to 1: 100.

Among the phenols with antioxidant action are partially as

Naturally occurring polyphenols for applications in the

pharmaceutical, cosmetic or nutritional field of particular interest. For example, the flavonoids or bioflavonoids, which are mainly known as plant dyes, frequently have an antioxidant potential. With effects of the substitution pattern of mono- and

Dihydroxy flavones deal with Lemanska et al., Current Topics in Biophysics 2000, 24 (2), 101-108. It is observed there that

Dihydroxyflavones having an OH group adjacent to the keto function or OH groups in 3'4'- or 6,7- or 7,8-position have antioxidant properties, while other mono- and Dihydroxyflavone partially have no antioxidant properties.

Quercetin (cyanidanol, cyanidolone 1522, meietin,

Sophoretine, ericin, 3,3 ', 4', 5,7-pentahydroxyflavone) as particular

called effective antioxidant (eg Rice-Evans et al., Trends in Plant Science 1997, 2 (4), 152-159). Lemanska et al., Free Radical Biology & Medicine 2001, 31 (7), 869-881, investigate the pH dependence of antioxidant effect of hydroxyflavones. Quercetin shows the highest activity of the investigated structures over the entire pH range.

The preparations according to the invention may contain vitamins as further ingredients. Preference is given to vitamins and vitamin derivatives selected from vitamin A, vitamin A propionate, vitamin A palmitate, vitamin A acetate, retinol, vitamin B, thiamin chloride hydrochloride (vitamin Bi), riboflavin (vitamin B ₂ ), nicotinamide, Vitamin C (ascorbic acid), vitamin D, ergocalciferol (vitamin D ₂ ), vitamin E, DL-oc-tocopherol, tocopherol-E-acetate, tocopherol hydrogen succinate, vitamin K1, esculin (vitamin P active ingredient), thiamin (vitamin bi), Nicotinic acid (niacin),

Pyridoxine, pyridoxal, pyridoxamine, (vitamin B ₆ ), pantothenic acid, biotin, folic acid and cobalamin (vitamin Bi ₂ ) in the inventive

Preparations contain, in particular preferably vitamin A palmitate, vitamin C and its derivatives, DL-a-tocopherol, tocopherol E acetate, nicotinic acid, pantothenic acid and biotin. Vitamins are with the

Preparations usually in cosmetic use in the range of 0.01 to 5 wt .-%, based on the total weight added.

The preparations according to the invention may additionally contain anti-aging active ingredients, anti-cellulite active ingredients or conventional skin-friendly or skin-care active ingredients. Skin-friendly or

In principle, skin-care active ingredients may be all active ingredients known to the person skilled in the art. Particularly preferred anti-aging agents are

Pyrimidinecarboxylic acids, aryloximes, bioflavonoids, bioflavonoid-containing extracts, chromones or retinoids.

Suitable anti-aging ingredients, especially for skin care

Preparations, are preferably also so-called compatible solutes. These are substances that are involved in the osmoregulation of

Plants or microorganisms are involved and made from these organisms can be isolated. Under the generic term compatible solutes also the described in the German patent application DE-A-10133202 osmolytes are taken. Suitable osmolytes are, for example, the polyols, methylamine compounds and amino acids and in each case their precursors. As osmolytes are in the sense of the Germans

 Patent application DE-A-10133202 especially substances from the group of polyols, such as myo-inositol, mannitol or sorbitol and / or understood one or more of the following osmolytically active substances: taurine, choline, betaine, phosphorylcholine, Glycerophosphorylcholine, glutamine, glycine , α-alanine, glutamate, aspartate, proline, and taurine. Precursors of these substances are, for example, glucose, glucose polymers, phosphatidylcholine, phosphatidylinositol, inorganic phosphates, proteins, peptides and polyamic acids. Precursors are e.g. Compounds that are converted into osmolytes by metabolic steps.

Preferably according to the invention as compatible solute substances selected from the group consisting of Pynmidincarbonsäuren (such as ectoine and hydroxyectoine), proline, betaine, glutamine, cyclic

Diphosphoglycerate, N-acetylornithine, trimethylamine N-oxide, di-myo-inositol phosphate (DIP), cyclic 2,3-diphosphoglycerate (cDPG), 1, 1-diglycerol phosphate (DGP), β-mannosylglycerate (Firoin) , β-Mannosylglyceramide (Firoin-A) or / and Di-mannosyl-di-inositol phosphate (DMIP) or an optical isomer, derivative, eg an acid, a salt or ester of these compounds or combinations thereof.

In particular, ectoine ((S) -1,5,6-tetrahydro-2-methyl-4-pyrimidinecarboxylic acid) and hydroxyectoine ((S, S) -1,4,5,6-tetrahydro-5 are among the pyrimidinecarboxylic acids hydroxy-2-methyl-4-pyrimidinecarboxylic acid) and their derivatives. Additional can be used as anti-aging active ingredients Merck products, such as 5,7-dihydroxy-2-methyl-chromone, marketed under the

Trade name RonaCare Luremin ^{®, ®} Ronacare isoquercetin, Ronacare ^® tiliroside or Ronacare ^® cyclopeptide be used. 5

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

Compounds of vitamin A. The described chromones and retinoids are also effective anti-cellulite agents. Another well-known anti-cellulite drug is caffeine.

In a further preferred embodiment of the invention, the preparation additionally contains at least one self-tanning substance. Such a preparation usually has a contrast-reducing effect and enables the achievement of an even skin tone. The extracts from plant parts of Eugenia uniflora can accordingly also be used according to the invention in combination with self-tanning substances for the purpose of reducing the contrast and achieving an even skin tone. A contrast reducing agent is a substance that has a

reduces uneven skin coloration by reducing the contrast between stronger and less-colored areas of the skin. In this case, such an uneven skin coloration can be caused by an uneven pigmentation and / or a different distribution of the cornea. Uneven pigmentation is in the

Population is not uncommon and is based on a different levels of melanin production of melanocytes or an irregular distribution of melanocytes in the skin. The combination of tanning mixtures based on the Maillard reaction or Michael addition with melanogenesis inhibiting substances causes already hyperpigmented skin areas to lose their high melanin concentrations and the hue generated by the colorant on the skin surface permeates over a large area.

In particular, a contrast reduction can be achieved by preparations comprising an extract of Eugenia uniflora plant parts with a self-tanning substance, preferably containing dihydroxyacetone (DHA) and derivatives derived therefrom, DHA rapid, DHA plus or erythrulose, or a mixture of self-tanning substances, preferably DHA, DHA rapid, containing DHA plus and / or erythrulose is combined. Advantageous self-tanning agents in a mixture or preparation containing dihydroxyacetone may be used inter alia: glycerolaldehyde, hydroxymethylglyoxal, γ-dialdehyde, 6-aldo-D-fructose, ninhydrin, 5-hydroxy-1,4-naphthoquinone (juglone) or 2-hydroxy - 1, 4-naphthoquinone (Lawson) or a mixture of said

Links. Erythrulose is particularly preferred in the

Dihydroxyacetone-containing mixture used.

Very particular preference is given to dihydroxyacetone or one of these

derived derivative used without further self-tanning substances. In the described preparations which contain an extract of plant parts of Eugenia uniflora and a self-tanner, it is also possible for color pigments to be present, the layer structure of the pigments not being limited. Preferably, the color pigment should be skin colored or brownish at a level of from 0.5 to 5% by weight. The selection of a

corresponding pigment is familiar to the expert.

The preparations described are particularly suitable for use in the lightening of skin, inhibition of tyrosinase and / or

Prophylaxis, treatment and / or follow-up of skin pigmentation disorders, in all cases especially hyperpigmentation,

Freckles, age spots, sun spots as well as environmental ones Skin aging. They are present in various dosage forms commonly used for this application.

As an application form of the preparations according to the invention, e.g. called: solutions, suspensions, emulsions, PIT emulsions, pastes, ointments, gels, creams, lotions, powders, soaps, surfactant-containing cleaning preparations, oils, aerosols, patches, envelopes, dressings and sprays, especially for external use. Other applications are e.g. Sticks, shampoos and shower baths. Further typical cosmetic application forms are also lipsticks, lip balms, powder, emulsion and wax make-up as well as sunscreen, pre-sun and after-sun preparations.

 Cosmetic and dermatological preparations according to the invention may in particular be an anhydrous preparation, a lotion or emulsion, such as cream or milk, or microemulsion, in each case of the water-in-oil (W / O) or of the oil-in-water type (O / W ), a multiple emulsion, for example of the type Waser-in-oil-in-water (W / O / W) or vice versa (O / W / O), gels or solutions (especially oily-alcoholic, oily-aqueous or aqueous alcoholic gels or solutions), a solid stick, an ointment or even an aerosol. For use, the cosmetic and dermatological according to the invention

Preparations applied in the usual manner for cosmetics on the skin in sufficient quantity. One embodiment of the invention is an emulsion which is present as cream or milk and, for example, fatty alcohols, fatty acids,

Fatty acid esters, in particular triglycerides of fatty acids, lanolin, natural and synthetic oils or waxes and emulsifiers in

Contains presence of water. Further particularly preferred

Embodiments provide oily lotions based on natural or synthetic oils and waxes, lanolin, fatty acid esters, especially triglycerides of fatty acids, or oily-alcoholic lotions a lower alcohol, such as ethanol, or a glycerol, such as

Propylene glycol, and / or a polyol, such as glycerol, and oils, waxes and fatty acid esters, such as triglycerides of fatty acids. A particularly preferred preparation according to the invention may also be present as an alcoholic gel containing one or more lower alcohols or polyols, such as ethanol, propylene glycol or glycerin, and a thickening agent such as silica. The oily-alcoholic gels also contain natural or synthetic oil or wax. The solid sticks are preferably made of natural or synthetic waxes and oils, fatty alcohols, fatty acids, fatty acid esters, lanolin and others

 Fatty substances. If a preparation is formulated as an aerosol, it is preferable to use the customary propellants, such as alkanes, air, nitrogen,

Nitrous oxide, more preferably alkanes or air. The extract, as described, can be incorporated in the usual way into cosmetic or dermatological preparations.

Any customary carrier substances, adjuvants and optionally further active ingredients can be added to the preparation. Preferable excipients come from the group of preservatives,

 Stabilizers, solubilizers, colorants, i. Pigments, dyes, emulsifiers or odor improvers.

The subject matter of the present invention accordingly also

Preparations, characterized in that a carrier suitable for cosmetic, pharmaceutical or / and dermatological applications and optionally physiologically acceptable auxiliaries and / or fillers are contained.

Suitable excipients and auxiliaries or fillers are described in detail in the following part. Ointments, pastes, creams and gels may contain the usual excipients suitable for topical administration, such as

animal and vegetable fats, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc and titanium dioxide or mixtures of these substances.

Powders and sprays may contain the usual carriers, e.g. Lactose, talc, silicic acid, aluminum hydroxide, calcium silicate and polyamide powder or mixtures of these substances. Sprays may additionally contain the usual volatile, liquefied propellants, e.g.

 Chlorofluorocarbons, propane / butane or dimethyl ether. Also, compressed air is advantageous to use. However, air can also be used in non-pressurized metering devices, such as e.g. Pump sprays, are used. Solutions and emulsions may be the usual carriers such as

 Solvents, solubilizers and emulsifiers, e.g. Water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol,

Benzyl benzoate, propylene glycol, 1, 3-butyl glycol, oils, in particular

Cottonseed oil, peanut oil, corn oil, olive oil, castor oil and sesame oil, glycerine fatty acid esters, polyethylene glycols and fatty acid esters of

Sorbitans or mixtures of these substances.

A preferred solubilizer in general is 2-isopropyl-5-methylcyclohexanecarbonyl-D-alanine methyl ester.

Suspensions may be the usual carriers such as liquid

Diluents, e.g. Water, ethanol or propylene glycol,

Suspending agents, e.g. ethoxylated isostearyl alcohols, polyoxyethylene sorbitol esters and polyoxyethylene sorbitan esters, microcrystalline

Cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth or mixtures of these substances. Soaps may contain the usual excipients such as alkali metal salts of fatty acids, salts of fatty acid monoesters, fatty acid protein hydrolysates, isothionates, lanolin, fatty alcohol, vegetable oils, plant extracts, glycerol, sugars or mixtures of these substances.

Surfactant-containing cleaning products, the usual carriers such as salts of fatty alcohol sulfates, fatty alcohol ether sulfates,

Sulfosuccinic monoesters, fatty acid protein hydrolysates, isothionates, imidazolinium derivatives, methyl taurates, sarcosinates,

Fatty acid amide ether sulfates, alkylamido betaines, fatty alcohols,

 Fatty acid diethanolamides, vegetable and synthetic oils, lanolin derivatives, ethoxylated glycerol fatty acid esters or mixtures of these substances. Facial and body oils may contain the usual carriers such as synthetic oils such as fatty acid esters, fatty alcohols, silicone oils, natural oils such as

Vegetable oils and oily vegetable extracts, paraffin oils, lanolin oils or mixtures of these substances. The preferred preparation forms according to the invention include in particular emulsions. O / W emulsions are particularly preferred. Emulsions, W / O emulsions and O / W emulsions are available in the usual way. Emulsions of the invention are advantageous and contain e.g. the said fats, oils, waxes and other fatty substances, and water or an aqueous phase, for example with solvents or hydrophilic surfactants, and an emulsifier, as is commonly used for such a type of preparation.

The lipid phase can be selected advantageously from the following

Group of substances:

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

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

 Fatty alcohols with lower alkanoic acids or with fatty acids;

Silicone oils, such as dimethylpolysiloxanes, diethylpolysiloxanes,

 Diphenylpolysiloxanes and mixed forms thereof. The oil phase of the emulsions, oleogels or hydrodispersions or lipodispersions in the context of the present invention is advantageously selected from the group of esters of saturated and / or unsaturated, branched and / or unbranched alkanecarboxylic acids having a chain length of 3 to 30 carbon atoms and saturated and / or or unsaturated,

branched and / or unbranched alcohols of a chain length of 3 to 30 carbon atoms, from the group of esters of aromatic carboxylic acid and saturated and / or unsaturated, branched and / or

unbranched alcohols of a chain length of 3 to 30 carbon atoms. Such ester oils can then be advantageously selected from the group

Isopropyl myristate, isopropyl palmitate, isopropyl stearate, isopropyl oleate, n

Butyl stearate, n-hexyl laurate, n-decyl oleate, isooctyl stearate, isononyl stearate, isononyl isononanoate, 2-ethylhexyl palmitate, 2-ethylhexyl laurate, 2-hexadecyl stearate, 2-octyl dodecyl palmitate, oleyl oleate, oleyl erucate,

Erucyl oleate, erucyl erucate and synthetic, semi-synthetic and natural mixtures of such esters, e.g. Jojoba oil. Furthermore, the

Oil phase can be advantageously selected from the group of branched and unbranched hydrocarbons and waxes, silicone oils, dialkyl ethers, the group of saturated or unsaturated, branched or unbranched alcohols, and the fatty acid triglycerides, namely the triglycerol esters of saturated and / or unsaturated, branched and / or unbranched alkanecarboxylic acids of a chain length of 8 to 24, in particular 12-18 C-atoms. The fatty acid triglycerides can For example, be selected from the group of advantageous

synthetic, semi-synthetic and natural oils, e.g. As olive oil, sunflower oil, soybean oil, peanut oil, rapeseed oil, almond oil, palm oil, coconut oil, palm kernel oil and the like. Any mixtures of such oil and wax components are also advantageous to use in the context of the present invention. It may also be advantageous, if appropriate, to use waxes, for example cetyl palmitate, as the sole lipid component of the oil phase. The aqueous phase of the preparations according to the invention may advantageously contain 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 analogous products, furthermore lower C number alcohols, e.g. Ethanol, isopropanol, 1, 2-propanediol, glycerol and in particular one or more

Thickening agents, which may be advantageously selected from the group of silica, aluminum silicates, polysaccharides and their derivatives, e.g. Hyaluronic acid, xanthan gum,

 Hydroxypropylmethylcellulose, particularly advantageous from the group of polyacrylates, preferably a polyacrylate from the group of so-called Carbopole, for example, Carbopols types 980, 981, 1382, 2984, 5984, each individually or in combination. In particular, mixtures of the abovementioned solvents are used. For alcoholic

Solvents can be another component of water.

In a preferred embodiment, the preparations according to the invention contain hydrophilic surfactants. The hydrophilic surfactants are preferably selected from the group of alkylglucosides, acyl lactylates, betaines and cocoamphoacetates. As emulsifiers, for example, the known W / O and O W emulsifiers can be used. It is advantageous to use further customary co-emulsifiers in the preferred O / W emulsions according to the invention.

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

It is advantageous to include the fatty alcohol ethoxylates from the group of

ethoxylated stearyl alcohols, cetyl alcohols, cetylstearyl alcohols

(Cetearyl alcohols).

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

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

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

Polyethylene glycol (24) stearate, polyethylene glycol (25) stearate,

Polyethylene glycol (12) isostearate, polyethylene glycol (13) isostearate,

Polyethylene glycol (14) isostearate, polyethylene glycol (15) isostearate,

Polyethylene glycol (16) isostearate, polyethylene glycol (17) isostearate,

Polyethylene glycol (18) isostearate, polyethylene glycol (19) isostearate,

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

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

Polyethylene glycol (24) isostearate, polyethylene glycol (25) isostearate,

Polyethylene glycol (12) oleate, polyethylene glycol (13) oleate,

Polyethylene glycol (14) oleate, polyethylene glycol (15) oleate,

Polyethylene glycol (16) oleate, polyethylene glycol (17) oleate, Polyethylene glycol (18) oleate, polyethylene glycol (19) oleate,

Polyethylene glycol (20) oleate.

As the ethoxylated alkyl ether carboxylic acid or its salt, the sodium laureth-11-carboxylate can be advantageously used. As the alkyl ether sulfate, sodium laureth-4 sulfate can be advantageously used. As the ethoxylated cholesterol derivative, polyethyleneglycol (30) cholesteryl ether can be advantageously used. Also Polyethyleng lycol (25) soybean oil has been proven. As ethoxylated triglycerides, the polyethylene glycol (60) Evening Primrose Glycerides can advantageously be used (Evening Primrose

= Evening primrose).

Furthermore, it is of advantage, the Polyethylenglycolglycerinfettsäureester from the group of polyethylene glycol (20) glyceryl laurate,

Polyethylene glycol (21) glyceryl laurate, polyethylene glycol (22) glyceryl laurate, polyethylene glycol (23) glyceryl laurate,

Polyethylene glycol (6) glycerylcaprat / cprinat,

 Polyethylene glycol (20) glyceryl oleate, polyethylene glycol (20) glyceryl isostearate, polyethylene glycol (18) glyceryl oleate (cocoate).

It is also beneficial to have the sorbitan esters from the group

Polyethylene glycol (20) sorbitan monolaurate,

Polyethylene glycol (20) sorbitan monostearate,

Polyethylene glycol (20) sorbitan monoisostearate,

Polyethylene glycol (20) sorbitan monopalmitate and

 Polyethylene glycol (20) to choose sorbitan monooleate.

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

Fatty alcohols having 8 to 30 carbon atoms, monoglycerol esters of saturated and / or unsaturated, branched and / or unbranched

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

Chain length of 8 to 24, in particular 12 to 18 C atoms,

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

Diglyceryl monostearate, diglyceryl monoisostearate,

 Propylene glycol monostearate, propylene glycol monoisostearate, propylene glycol monocaprylate, propylene glycol monolaurate, sorbitan monoisostearate,

Sorbitan monolaurate, sorbitan monocaprylate, sorbitan monoisooleate,

Sucrose distearate, cetyl alcohol, stearyl alcohol, arachidyl alcohol, behenyl alcohol, isobehenyl alcohol, selachyl alcohol, chimyl alcohol,

Polyethylene glycol (2) stearyl ether (steareth-2), glyceryl monolaurate,

Glyceryl monocaprinate, glyceryl monocaprylate or PEG-30 dipolyhydroxystearate.

The preparation may contain cosmetic adjuvants which are commonly used in this type of preparation, e.g.

Thickeners, emollients, moisturizers,

surfactants, emulsifiers, preservatives, antifoaming agents, perfumes, waxes, lanolin, propellants, dyes and / or pigments that color the agent itself or the skin, and other ingredients commonly used in cosmetics.

As dispersion or solubilizing agent, an oil, wax or other fatty substance, a low monoalcohol or a low

Use polyol or mixtures thereof. Particularly preferred monoalcohols or polyols include ethanol, i-propanol, propylene glycol, glycerine and sorbitol. The present invention also provides a process for

Preparation of a preparation as described above, characterized

in that an extract of Eugenia uniflora is mixed with at least one carrier suitable for topical applications and optionally with physiologically acceptable excipients and / or fillers.

 The preparations according to the invention can be used with the aid of

Techniques well known to those skilled in the art. The mixing may result in dissolution, emulsification or dispersion of the extract as described above in the carrier. The prior teaching of the invention and its embodiments relating to the extract and preparations thereof is valid and applicable without restriction to the preparation of the preparation, if it appears expedient.

Another embodiment of the present invention relates to a pharmaceutical composition containing an extract of plant parts of Eugenia uniflora.

A "drug", "drug" as well as a "pharmaceutical

Composition "," pharmaceutical formulation "or

"Pharmaceutical preparation" here is any agent which in the prophylaxis, therapy, follow-up or treatment of

Patients can be used, at least temporarily a pathogenic Show modification of the overall state or condition of individual parts of the patient organism, preferably as a result of pigmentary disorders of the skin. To increase the protective or therapeutic effect of the compounds of the invention, pharmaceutically acceptable

Adjuvants are added. For the purposes of the invention, any substance that enables, enhances or modifies the extracts according to the invention is an "adjuvant." Known adjuvants are, for example, aluminum compounds such as aluminum hydroxide or aluminum phosphate, saponins such as QS 21, muramyl dipeptide or

Muramyl tripeptide, proteins, e.g. Gamma interferon or TNF, MF 59, phosphate dibylcholine, squalene or polyols. Furthermore, DNA encoding a protein with adjuvant effect can be administered in parallel or in a construct.

The introduction of the pharmaceutical agent into a cell or an organism according to the invention can be done in any way that allows tyrosinase with those in the

Composition brought into contact and as a result a response is induced. The pharmaceutical agent of the present invention may be administered orally, topically, transdermally, transmucosally, transurethally, vaginally, rectally, pulmonarily, enterally and / or parenterally, preferably topically or transdermally. The chosen mode of administration depends on the indication to be given

administering dose, individual-specific parameters, etc.

In particular, the different modes of administration allow for site-specific therapy that minimizes side effects and that

Reduced drug dose.

The dosage forms of the pharmaceutical agent are mixed with the usual solid or liquid carriers and / or diluents and the excipients commonly used according to the desired mode of administration in a suitable dosage and in a conventional manner. In principle, therefore, pharmaceutically acceptable excipients known to those skilled in the art may form part of the pharmaceutical composition of the invention, the amount of excipient material combined with the active ingredient to produce a single dosage varying with the individual to be treated and the mode of administration. These pharmaceutically acceptable additives include salts, buffers, fillers, stabilizers, chelating agents, antioxidants, solvents, binders, lubricants,

Tablet coatings, flavors, colors, preservatives, sizing agents and the like. Examples of such excipients are water, vegetable oils, benzyl alcohols, alkylene glycol, polyethylene glycol,

Glycerol triacetate, gelatin, carbohydrates, e.g. Lactose or starch, magnesium stearate, talc and Vaseline.

The pharmaceutical formulation may be in the form of tablet, film-coated tablet, dragee, lozenge, capsule, pill, powder, granule, syrup, juice, drops, solution, dispersion, suspension, suppository, emulsion, implant, cream, gel, ointment, paste, lotion, serum , Oil, spray, aerosol, glue, plaster or dressing. The oral dosage form used is preferably tablets, film-coated tablets, dragees, lozenges, capsules, pills, powders, granules, syrups, juices, drops, solutions, dispersions or

Suspensions - also prepared as depot form. Furthermore, parenteral dosage forms such as e.g. Suppositories, suspensions,

Emulsions, implants or solutions to be considered,

preferably oily or aqueous solutions. For topical administration, the active pharmaceutical ingredient is at least one pharmaceutical

acceptable carrier, such as microcrystalline cellulose, and optionally further excipients, such as moisturizers, to be applied to the skin solid formulations, such as creams, gels, ointments, pastes, powders or emulsions or to be applied to the skin liquid formulations, such as solutions, suspensions, lotions, serums, oils, sprays or aerosols in the usual way.

Preferably, the pharmaceutical agent is for topical application. The pharmaceutical agent may also be present as a solid composition, for example in the lyophilized state, and then by addition of a dissolving agent, such as e.g. distilled water, before the

Use to be prepared. The basics of making

Lyophilisates are familiar to the skilled worker. The concentration of the extract in the formulation may be 0.01 to 99

Percent by weight. It is crucial that the pharmaceutical composition comprises as active ingredient an effective amount of the extract together with the pharmaceutically acceptable excipients. The terms "effective amount" or "effective dose" are used herein

used interchangeably and denote a lot of

pharmaceutical agent having a prophylactic or therapeutically relevant effect on a disease or pathological change in the cell, tissue, organ or mammal. A "prophylactic effect" prevents the onset of a disease and includes an increase in the normal physiological function prophylaxis is particularly advisable when an individual has predispositions for the onset of the aforementioned diseases, such as a family history, a genetic defect or a recent Disease A "therapeutically relevant effect" partially or wholly relieves one, several or all disease symptoms or results in the partial or complete return of one or more or all of the physiological or biochemical parameters associated with or causative of the disease or pathological change , in the normal state. Also, follow-up is understood as a type of therapeutic treatment when the extract is administered at certain intervals, eg to completely eliminate the symptoms of a disease. The dose or dose range for the dose is large enough to achieve the desired prophylactic or therapeutic effect of inducing a biological or medical response. In general, the dose will vary with the age, constitution and gender of the patient, as well as the severity of the disease. It is understood that the specific dose, frequency and duration of administration of a variety of

Depend on factors such as the targeting and binding ability of the compounds, nutritional habits of the to be treated

Individual, mode of administration, excretion rate and combination with other medications. The individual dose can be adjusted both in relation to the primary illness and in relation to the occurrence of possible complications. The exact dose is through one

Detectable by known means and methods. In one embodiment of the invention, in order to promote the medicinal effect, the pharmaceutical composition may also comprise one or more further active ingredients, simultaneous or sequential administration being conceivable. The therapeutic effect of the pharmaceutical composition according to the invention may be, for example, that the inhibition of the

 Tyrosinase as a desired side effect certain skin brightener work better or by reducing the dose, the number of

Side effects of these drugs is reduced. The use of extracts of plant parts of Eugenia unifiora for skin lightening has the advantage that even at very low

Concentration to achieve a powerful effect. They show advantageous high and long-lasting activity in terms of their effect as

skin lightening agents. In addition, the extracts are also characterized by high application safety and good formulatability. So they are easy to incorporate into preparations and have increased stability in the preparations. In particular, are water extracts advantageous because they are water-soluble and thus very easy to incorporate. Also, the preparation of the extracts is advantageous, since in particular the production of the water extract is particularly environmentally friendly. Even without further statements, it is assumed that a person skilled in the art can make the most of the above description. All mentioned as well as further constituents or components are familiar to the person skilled in the art and can undergo a special design for the teaching according to the invention in routine experiments. All documents cited in the specification are hereby incorporated by reference in their entirety in the disclosure of the present invention.

In the following, the invention will be explained in more detail by way of non-limiting examples and figures for specific embodiments.

Fig. 1:

 Fig. 1 shows the HPLC chromatograms of the extract of Eugenia uniflora (a) and of pure eugenin (b) in comparison. The signal of

Comparative sample Eugenin appears at a retention time of approx. 7 min. At this retention time, the extract has no signal (see Example 3).

Examples: Example 1: Extracts from Eugenia uniflora

 Approximately 3.5 g Eugenia uniflora leaves (plant available from the Dehner garden trade in Munich, Germany) are dried to constant weight at 40 ° C. and 200 mbar in a vacuum drying cabinet, coarsely crushed and extracted in an ultrasonic bath at 70 ° C. for 45 minutes.

1, 531 g of plant material are extracted with 40 ml of water, giving a yellow-brown clear solution. 1, 503 g are extracted with 40 ml of ethanol, giving a green clear solution.

 The solvent is removed. There are obtained 190 mg of water extract and 80 mg of ethanol extract.

Example 2: Performance of the B16 V Mouse Melanoma Cell Assay:

B16V mouse melanoma cells (manufacturer: DSMZ, article number: ACC370) are mixed in RPMI medium (Invitrogen, article no .: 31870), which additionally contains 10% FBS (fetal bovine serum; Invitrogen, article no: 10499044 ), 2 mM L-glutamine (Invitrogen, item no: 25030) and 1 mM sodium pyruvate (Invitrogen, item no: 11360) are added and incubated for 72 h at 37 ° C and 5% C0 ₂ . The medium is separated and the cells are washed once with 10mL DPBS (Dulbecco's Phosphate-Buffered Salines, Invitrogen, Item No. 14190) and the medium is then aspirated. 1 mL of HyQtase-Cell Detachment Solution (Hyclone,

Article no. SV30030.01) on the cells. The bottle is swiveled several times and the HyQtase- Cell Detachment Solution is then removed by suction. Then the cells are incubated for 5 min in the incubator at 37 ° C and 5% C0 ₂ . The cells are taken up in the modified RPMI medium (see above) and the number of cells determined. For this, the cells are stained with trypan blue and counted in a Neubauer counting chamber. Subsequently, the cells are seeded again in the modified RPMI medium (see above) in a defined cell number of 80,000 cells per well (6-well Clear Plate, TCT, PS (Nunc)).

The cells are incubated for 24 h at 37 ° C. and 5% CO 2, after which the medium is removed. Subsequently, 1980 L of the substance dilution

added. For this dilution of the substance, the water extract from Example 1 is dissolved in DMSO and then filtered through a sterile filter (0.2 m, Millipore, Article No. SLLG0 3SL). The solution is then mixed with the modified RPMI medium (see above, but in this case the FBS Content only 5%) so that the final concentration of the extract is 0.1 mg / ml or 9.95 mg / ml.

Then 20 μΙ_ of an alpha-MSH solution (alpha-melanocyte stimulating hormone, DMSO, Sigma, Article No.: D2650) is added such that the alpha-MSH concentration in the well is 10 ^-8 M. Subsequently, the mixture is again incubated at 37 ° for 24 h washed ° C and 5% _CO2. the process described in this section as a whole is repeated twice more. After the final incubation period, the media is aspirated and the cells with 1000μΙ_ DPBS (Invitrogen, product no. 14190). the medium is again 250μΙ_ HyQtase-Cell

Detachment Solution (Hyclone, Item No. SV30030.01) is added to the cells. The 6-well plate is pivoted several times and the HyQtase- Cell Detachment Solution is then removed by suction. Then the cells are incubated for 5 min in the incubator at 37 ° C and 5% C0 ₂ . The cells are taken up in 1.5 ml of DPBS (Invitrogen, Item No. 14190) and transferred to a cup (SARSTEDT, Ref. 72.692.005). Subsequently, the cell number is determined. For this, the cells are stained with trypan blue and counted in a Neubauer counting chamber. Centrifuge the cells at 3500g for 1min. The obtained pellets are photographed and

then the supernatant is sucked off. The pellets are dissolved in 1 mL N NaOH for 1 h at 80 ° C and then cooled to RT. Then 200μΙ_ (as quadruple determination) are pipetted four times per cup into a 96 well plate (VWR, article no. 4100636981) and the absorption at 405 nm wavelength determined (Safire, Tecan). By means of a calibration line, the content of melanin can be determined

As a comparison, a sample without extract but with 0.1% DMSO or with 0.1% DMSO and alpha-MSH (concentration in the well at 10 ^"8 M) is used in parallel. Results:

 The water extract from Eugenia uniflora from Example 1 causes a

Reduction of melanin content by α-MSH for tanning

stimulated melanocytes. In the case of an extract concentration of 0.1 mg / ml, the melanin content of the cells even falls below the melanin content of the unstimulated cells

Table 1: Content of melanin per cell:

Example 3: Examination of the Eugenia tyn / T / ora extract on eugenin:

Since eugenin is soluble in ethanol, the ethanol extract of Example 1 is analyzed by HPLC. For comparison, pure eugenin (purity 99%) is measured.

The conditions for the HPLC are as follows:

Column: Chromolith Performance RP-18e 100- 4.6 mm

Eluent A: acetonitrile + 1% water

 Eluent B: 0.1 M sodium dihydrogen phosphate buffer pH 2.6 + 1% acetonitrile gradient:

Wavelength: 3 5 nm The HPLC chromatograms of the extract of Eugenia uniflora (a) and of pure eugenin (b) have no agreement (see Fig. 1): The chromatogram of the extract consists of 3 signals in one

Retention time of approx. 2 to 3 min. The signal of the comparative sample Eugenin appears at a retention time of approx. 7 min. At this retention time, the chromatogram of the extract has no signal. The results show that the examined extracts do not contain eugenin.

Example 4: O / W emulsions for skin lightening, data in% by weight

Ingredients 1 -1 1-2 1-3 1-4 1-5

Titanium dioxide 2 5

 Methylene bis

Benztriazolyltetramethylbuty

 Iphenol

 Eugenia uniflora extract 0,5 0,25 0,1 0,25 0,1

4-methylbenzylidene camphor 2 3 4

BMDBM 1 3 3 3

Stearyl alcohol (and) 3 3 3 3 3 steareth-7 (and) steareth-10

 Glyceryl stearate (and) 3 3 3 3 3 ceteth-20

 Glyceryl stearate 3 3 3 3 3

Microwax 1 1 1 1 1

Cetearyl octanoate 1 1, 5 1 1, 5 1 1, 5 1 1, 5 11, 5

Caprylic / Capric triglyceride 6 6 6 6 6

Oleyl oleate 6 6 6 6 6

Propylene glycol 4 4 4 4 4

Propylparaben 0.05 0.05 0.05 0.05 0.05

Methyl paraben 0.15 0.15 0.15 0.15 0.15

Tromethamine 1, 8

Water Ad 100 Ad 100 Ad 100 Ad 100 Ad 100 Example 4 (continued):

Ingredients 1-6 1-7 1-8 1-9 1-10

Titanium dioxide

 Methylene bis-1 2 1

 Benztriazolyltetramethylbuty

 Iphenol

 Eugenia uniflora extract 2.0 1, 0 1, 0 0.5 0.1

4-methylbenzylidene camphor 3 2

 BMDBM 3 3 3 3

 Stearyl alcohol (and) 3 3 3 3 3 steareth-7 (and) steareth-10

 Glyceryl stearate (and) 3 3 3 3 3 ceteth-20

 Glyceryl stearate 3 3 3 3 3

Microwax 1 1 1 1 1

Cetearyl octanoate 11, 5, 11, 5, 11, 5, 11, 5, 11, 5

Caprylic / Capric triglyceride 6 6 6 6 6

Oleyl oleate 6 6 6 6 6

Propylene glycol 4 4 4 4 4

Propylparaben 0.05 0.05 0.05 0.05 0.05

Methylparaben 0.15 0.15 0.15 0.15 0.15

tromethamine

Water Ad 100 Ad 100 Ad 100 Ad 100 Ad 100

Example 5: W / O emulsions for skin lightening, data in% by weight

Ingredients 2-1 2-2 2-3 2-4 2-5

Titanium dioxide 2 5

 Eugenia uniflora extract 0,5 0,25 0,1 0,25 0,1

zinc oxide

 Polyglyceryl-3-dimerate 3 3 3 3 3

Cera alba 0.3 0.3 0.3 0.3 0.3

Hydrogenated castor oil 0.2 0.2 0.2 0.2 0.2

Paraffinum liquidum 7 7 7 7 7

Caprylic / capric 7 7 7 7 7 triglycerides

 Hexyl laurate 4 4 4 4 4

PVP / eicosenic copolymer 2 2 2 2 2

Propylene glycol 4 4 4 4 4

Magnesium sulfate 0.6 0.6 0.6 0.6 0.6

Tocopherol 0.5 0.5 0.5 0.5 0.5

Tocopherol acetate 0.5 0.5 0.5 0.5 0.5

Cyclomethicone 0.5 0.5 0.5 0.5 0.5

Propylparaben 0.05 0.05 0.05 0.05 0.05

Methyl paraben 0.15 0.15 0.15 0.15 0.15

Water Ad 100 Ad 100 Ad 100 Ad 100 Ad 100

Example 5 (continued):

Ingredients 2-6 2-7 2-8 2-9 2-10

Titanium dioxide

 Eugenia uniflora extract 0.5 1, 0 1, 0 0.5 0.1

Zinc oxide 5 2

Polyglyceryl-3-dimerate 3 3 3 3 3

Cera alba 0.3 0.3 0.3 0.3 0.3

Hydrogenated castor oil 0.2 0.2 0.2 0.2 0.2

Paraffinum liquidum 7 7 7 7 7

Caprylic / capric 7 7 7 7 7 triglycerides

 Hexyl laurate 4 4 4 4 4

PVP / eicosenic copolymer 2 2 2 2 2

Propylene glycol 4 4 4 4 4

Magnesium sulfate 0.6 0.6 0.6 0.6 0.6

Tocopherol 0.5 0.5 0.5 0.5 0.5

Tocopherol acetate 0.5 0.5 0.5 0.5 0.5

Cyclomethicone 0.5 0.5 0.5 0.5 0.5

Propylparaben 0.05 0.05 0.05 0.05 0.05

Methyl paraben 0.15 0.15 0.15 0.15 0.15

Water Ad 100 Ad 100 Ad 100 Ad 100 Ad 100

Example 6 Cream for Contrast Reduction (in% by Weight)

Ingredients INCI [%] A

 Marlipal 1618/11 CETEARETH-1 1 3.00 La nice O CETEARYLALCOHOL 7.00 Luvitol EHO CETEARYLOCTANOATE 5.00 Tegosoft TN C12-15 ALKYL BENZOATE 2.50 Miglyol 812 N CAPRYLIC / CAPRIC 2.50

 TRIGLYCERIDES

 Propyl 4-hydroxybenzoate PROPYLPARABEN 0,05

B

 1, 2-propanediol PROPYLENE GLYCOL 4.00 Methyl 4-hydroxybenzoate METHYLPARABEN 0,15 Water, demineralized AQUA (WATER) 60,80 Eugenia uniflora Extract 1, 00 C

 Dihydroxyacetone DIHYDROXYACETONE 5.00

Water, demineralized AQUA (WATER) 9.00

production:

Heat phase A to 75 ° C, phase B to 80 ° C. Slowly add phase B into phase A with stirring. Homogenize. Allow to cool with constant stirring and add phase C at 40 ° C.

Example 7 Lotion for Contrast Reduction

Ingredients INCI [%] A

 Dow Corning 3225 C CYCLOMETHICONE, 23,60

 DIMETHICONE COPOLYOL

 Propyl 4-hydroxybenzoate PROPYLPARABEN 0,05

B

 Dihydroxyacetone DIHYDROXYACETONE 5.00 Methyl 4-hydroxybenzoate METHYLPARABEN 0,15

Eugenia uniflora extract 1, 00

1, 2-Propanediol PROPYLENE GLYCOL 34.90

Water, demineralized AQUA (WATER) 35,30

production:

Phase B completely dissolved to phase A give.

Example 8: Gel for Contrast Reduction

Ingredients INCI [%] A

 Dihydroxyacetone D I H YD ROXYAC ETO N E 5.00 1, 2-Propanediol PROPYLENE GLYCOL 2.50 Sorbitol F liquid SORBITOL 2.50 Methyl 4-hydroxybenzoate METHYLPARABEN 0,20 Water, demineralized AQUA (WATER) 28,30

B

 Eugenia uniflora extract 1, 00 Natrosol 250 HHR HYDROXYETHYL CELLULOSE 1, 50 water, demineralized AQUA (WATER) 59.00

production:

 Add Natrosol to water phase B with vigorous stirring. The dosage of the addition must be such that although a uniform distribution of the particles and a complete wetting of the same can be done with water, while the viscosity of the aqueous phase is minimized while the polymer is added. Dissolve dihydroxyacetone in the water of phase A and add remaining ingredients with stirring. Combine phase A and B and homogenize.

Claims

claims

1. Use of an extract of plant parts of Eugenia uniflora for lightening the skin.

2. Use according to claim 1 for the inhibition of tyrosinase.

3. Use according to claim 1 for the prophylaxis, treatment and / or follow-up of pigmentary disorders of the skin.

4. Use according to claim 3, characterized in that the

 Pigment disorders from the group of hyperpigmentation,

 Freckles, age spots and sunspots are selected.

Use according to one or more of claims 1 to 4, characterized in that the plant parts are leaves, flowers or fruits.

Use according to claim 5, characterized in that the plant parts are leaves.

Preparation containing an extract of Eugenia uniflora and one or more UV filters.

A preparation comprising an extract of Eugenia uniflora and at least one further active substance or extract with one

 skin lightening activity.

9. A preparation according to claim 7 or 8, characterized in that the preparation contains 0.01 to 99 wt.% Of the extract of Eugenia uniflora, based on the total weight of the preparation contains.

10. Preparation according to one or more of claims 7 to 9, characterized in that a suitable for cosmetic, pharmaceutical and / or dermatological applications carrier and optionally physiologically acceptable excipients and / or fillers are included.

1 1.A method for preparing a preparation according to one or more of claims 7 to 10, characterized in that an extract of Eugenia uniflora with at least one suitable for topical applications carrier and optionally with physiologically acceptable

Excipients and / or fillers is mixed.