EP1979055A2

EP1979055A2 - Use of protein microbeads in cosmetics

Info

Publication number: EP1979055A2
Application number: EP07712054A
Authority: EP
Inventors: Burghard Liebmann; Marcus Fehr; Arne Ptock; Thomas Scheibel; Daniel HÜMMERICH
Original assignee: BASF SE
Current assignee: BASF SE
Priority date: 2006-01-20
Filing date: 2007-01-19
Publication date: 2008-10-15
Also published as: US20100278882A1; CN101370481A; JP5236498B2; WO2007082923A2; CN101370556A; WO2007082923A3; US8288512B2; US20100278883A1; EP1978937A1; WO2007082936A1; CA2637065C; CA2638870A1; CN104856962A; CA2637065A1; JP2009523767A; JP2009523766A

Abstract

The invention relates to the use of protein microbeads in cosmetics.

Description

Use of protein microbeads in cosmetics

The present invention relates to the use of protein microbeads in cosmetics, in particular in skin cosmetics

State of the art

EP 1 110534 describes a cosmetic product of ultrafine crystalline silk powder which is prepared by treating silk under alkaline conditions at a temperature above 100 ° C. and subsequent mechanical comminution.

Description of the invention

The present invention relates in a first embodiment to the use of protein microbeads in cosmetics.

Protein microbeads (i)

Protein microbeads consist of polypeptides composed of amino acids, in particular of the 20 naturally occurring amino acids. The amino acids may also be modified, for example, acetylated, glycosylated, farnesylated.

Furthermore, the protein microbeads have a globular shape with an average particle diameter of 0.1 to 100, in particular from 0.5 to 20, preferably from 1 to 5 and particularly preferably from 2 to 4 microns.

Protein microbeads can preferably be prepared by the method described below:

The protein is dissolved in a first solvent. As the solvent, for example, aqueous salt solutions can be used. In particular, highly concentrated salt solutions with a concentration greater than 2, in particular greater than 4 and particularly preferably greater than 5 molar, whose ions have more pronounced chaotropic properties than sodium and chloride ions. An example of such a saline solution is 6 M guanidinium thiocyanate or 9 M lithium bromide. Furthermore, organic solvents can be used to dissolve the proteins. In particular, fluorinated alcohols or cyclic hydrocarbons are suitable. Examples are hexafluoroisopropanol and cyclohexane. The preparation of the protein microbeads can be carried out in the solvents described. Alternatively, this This solvent can be replaced by another solvent, for example, low-concentration salt solutions (c <0.5 M) by dialysis or dilution. The final concentration of the dissolved protein should be between 0.1 - 100 mg / ml. The temperature at which the process is carried out is usually 0-80, preferably 5 -50 and more preferably 10 - 40 ° C.

If aqueous solutions are used, they may also be mixed with a buffer, preferably in the range from pH 4 to 10, particularly preferably 5 to 9, very particularly preferably 6 to 8.5. Addition of an additive induces phase separation. This results in a protein-rich phase emulsified in the mixture of solvent and additive. Due to surface effects, emulsified protein-rich droplets take on a round shape. By choosing the solvent, the additive and the protein concentration, the average diameter of the protein microbeads can be adjusted to values between 0.1 μm to 100 μm.

As an additive, it is possible to use all substances which, on the one hand, are miscible with the first solvent and, on the other hand, induce the formation of a protein-rich phase. When microbead formation is carried out in organic solvents, organic substances having a lower polarity than the solvent, e.g. Toluene. In aqueous solutions salts can be used as an additive whose ions have more pronounced cosmotropic properties than sodium and chloride ions (e.g., ammonium sulfate, potassium phosphate). The final concentration of the additive should be between 1% and 50% by weight, based on the protein solution, depending on the type of additive.

The protein-rich droplets are fixed by curing, whereby the round shape is retained. The fixation is based on the formation of strong intermolecular interactions. The nature of the interactions may be noncovalent, eg by the formation of intermolecular β-sheet crystals or covalent, eg by chemical crosslinking. The curing can be carried out by the additive and / or by the addition of another suitable substance. The curing takes place at temperatures between 0 and 80 ° C, preferably between 5 and 60 ° C. This further substance can be a chemical cross-linker. A chemical cross-linker is understood to mean a molecule in which at least two chemically reactive groups are connected to one another via a linker. Examples of these are sulfhydryl-reactive groups (for example maleimides, pydridyl disulfides, α-haloacetyls, vinyl sulfones, sulfatoalkyl sulfones (preferably sulfatoethyl sulfones)), amine-reactive groups (for example succinimidyl esters, carbodiimde, hydroxymethyl phosphine, imido esters, PFP esters, aldehydes, isothiocyanates, etc .), Carboxy-reactive groups (eg, amines, etc.), hydroxyl-reactive groups (eg, isocyanates, etc.), unselective groups (eg, arylazides, etc.), and photoactivatable groups (eg, perfluorophenyl azide, etc.). These reactive groups can form covalent linkages with amine, thiol, carboxyl or hydroxyl groups present in proteins.

The stabilized microbeads are washed with a suitable further solvent, e.g. Water and then dried by methods known to those skilled in the art, e.g. by lyophilization or spray drying. The success of the sphere formation is checked by scanning electron microscopy.

Suitable proteins for the production of protein microbeads are proteins which are predominantly intrinsically unfolded in aqueous solution. For example, this condition can be calculated using an algorithm based on the ILJpred program (http://iupred.enzim.hu/index.html; The Pairwise Energy Content Estimated from Amino Acid Composition Discriminates between Folded and Intrinsically Unstructured Zsuzsanna Dosztanyi, Veronika Csizmόk, Peter Tompa and Istvan Simon, J. Mol. Biol. (2005) 347, 827-839). A predominantly intrinsically unfolded state is assumed when a value> 0.5 is calculated for over 50% of the amino acid residues according to this algorithm (prediction type: long disorder).

Suitable proteins for the production of protein microbeads are silk proteins. By this we mean below those proteins which contain highly repetitive amino acid sequences and are stored in the animal in a liquid form and in whose secretion by shearing or spinning fibers are formed. (Craig, C.L. (1997) Evolution of arthropod silks. Annu. Rev. Entomol. 42: 231-67).

Particularly suitable proteins for the production of protein microbeads are spinel silk proteins, which in their original form could be isolated from spiders. Especially suitable proteins are silk proteins which could be isolated from the "major ampullate" gland of spiders.

Preferred silk proteins are ADF3 and ADF4 from the "major ampullate" gland of Araneus diadematus (Guerette et al., Science 272, 5258: 112-5 (1996)).

Equally suitable proteins for the production of protein microbeads are natural or synthetic proteins which are derived from natural silk proteins and which have been produced heterologously in prokaryotic or eukaryotic expression systems using genetic engineering methods. Nonlimiting examples of prokaryotic expression organisms are Escherichia coli, Bacillus subtilis, Bacillus megaterium, Corynebacterium glutamicum, etc. Nonlimiting examples of eukaryotic expression organisms are yeasts such as Saccharomyces cerevisiae, Pichia pastoris and others, filamentous fungi such as Aspergillus niger, Aspergillus oryzae and Aspergillus nidulans. Trichoderma reesei, Acremonium chrysogenum and others, mammalian cells, such as Heia cells, COS cells, CHO cells and others, insect cells, such as Sf9 cells, MEL cells and others.

Particularly preferred for the production of protein microbeads are synthetic proteins which are based on repeat units of natural silk proteins. In addition to the synthetic repetitive silk protein sequences, these may additionally contain one or more natural non-repetitive silk protein sequences (Winkler and Kaplan, J Biotechnol 74: 85-93 (2000)).

Among the synthetic silk proteins preferred for the production of protein microbeads are synthetic spider silk proteins which are based on repeat units of natural spider silk proteins. In addition to the synthetic repetitive spider silk protein sequences, these may additionally contain one or more natural non-repetitive spider silk protein sequences. Among the synthetic spider silk proteins, the sg. C16 protein (Huemmerich et al., Biochemistry, 43 (42): 13604-13612 (2004)). This protein has the polypeptide sequence shown in SEQ ID NO: 1. In addition to the polypeptide sequence shown in SEQ ID NO: 1, particularly functional equivalents, functional derivatives and salts of this sequence are also preferred. According to the invention, "functional equivalents" are in particular also understood as meaning mutants which have a different amino acid than the one specifically mentioned in at least one sequence position of the abovementioned amino acid sequences but nevertheless possess one of the abovementioned biological properties or multiple amino acid additions, substitutions, deletions and / or inversions of available mutants, said changes may occur in any sequence position, as long as they lead to a mutant with the property profile according to the invention. Functional equivalence is given in particular even if the reactivity patterns between the mutant and the unchanged polypeptide match qualitatively.

"Functional equivalents" in the above sense are also "precursors" of the described polypeptides as well as "functional derivatives" and "salts" of the polypeptides.

"Precursors" are natural or synthetic precursors of the polypeptides with or without the desired biological activity.

Examples of suitable amino acid substitutions are shown in the following table:

Original rest Examples of substitution

AIa Ser

Arg Lys

Asn GIn; His

Asp Glu

Cys Ser

GIn Asn

Giu Asp

GIy Pro

His Asn; Gin

Ne Leu; Val

Leu Ne; Val

Lys Arg; GIn; Glu

Met Leu; ne

Phe Met; Leu; Tyr

Ser Thr Thr Ser

Trp Tyr

Tyr Trp; Phe

VaI Ne; Leu

Salts are understood as meaning both salts of carboxyl groups and acid addition salts of amino groups of the protein molecules according to the invention. Sacks of carboxyl groups can be prepared in a manner known per se and include inorganic salts, such as, for example, sodium, calcium and ammonium salts. , Iron and zinc salts, and salts with organic bases, such as amines, such as triethanolamine, arginine, lysine, piperidine, etc. Acid addition salts, such as salts with mineral acids, such as hydrochloric acid or sulfuric acid and salts with organic acids, such as acetic acid and Oxalic acid are also the subject of the invention.

"Functional derivatives" of polypeptides of the invention may also be produced at functional amino acid side groups or at their N- or C-terminal end by known techniques Such derivatives include, for example, aliphatic esters of carboxylic acid groups, amides of carboxylic acid groups obtainable by reaction with ammonia or with a primary or secondary amine; N-acyl derivatives of free amino groups prepared by reaction with acyl groups; or O-acyl derivatives of free hydroxy groups prepared by reaction with acyl groups.

Another object of the invention are protein microbeads consisting of couplings of a protein (i) and an effector molecule (ii). As protein (i), all the above-mentioned proteins are suitable. The protein (i) can either already be present as a protein microbead and then be coupled with an effector molecule (ii), or the protein (i) is not present as a protein microbead and is coupled with the effector molecule (ii) and only Subsequently, the coupled molecule is transferred into a protein microbead or the coupling takes place during the phase separation. Effector molecules (N)

In the following, the term "effector molecule (N)" refers to molecules which have a certain, predictable effect. These can be either proteinaceous molecules, such as enzymes or else non-proteinogenic molecules such as dyes, light stabilizers, vitamins, provitamins, antioxidants and fatty acids, conditioners or metal-containing compounds.

Among the proteinaceous effector molecules, enzymes and antibodies are preferred. Among the enzymes, the following are preferred as effector molecules (ii): oxidases, peroxidases, proteases, glucanases, mutanase, tyrosinases, laccases, metal-binding enzymes, lactoperoxidase, lysozyme, amyloglycosidase, glucose oxidase, superoxide dismutase, photolyase, T4 endonuclease, catalase, Thioredoxin, thioredoxin reductase. In the case of the proteinaceous but non-enzymatically active effector molecules, the following are preferred as effector molecules (ii): antimicrobial peptides, hydrophobins, collagen, carotenoid-binding proteins, heavy metal-binding proteins, odorant-binding proteins, cellulose-binding proteins, starch-binding proteins, keratin-binding proteins.

Also suitable as proteinaceous effector molecules (ii) are hydrolysates of proteins from plant and animal sources, for example hydrolyzates of proteins of marine origin.

Among the non-proteinaceous effector molecules (ii), carotenoids are preferred. According to the invention, carotenoids are to be understood as meaning the following compounds and their esterified or glycosylated derivatives: .beta.-carotene, lycopene, lutein, astaxanthin, zeaxanthin, cryptoxanthin, citranaxanthin, canthaxanthin, bixin, .beta.-apo-4-carotenal, .beta.-apo 8 -carotinal, β-apo-8-carotenoic acid ester, neurospores, echinenone, adonirubin, violaxxin, torules, torularhodin, singly or as a mixture. Preferably used carotenoids are β-carotene, lycopene, lutein, astaxanthin, zeaxanthin, citranaxanthin and canthaxanthin.

Further preferred effector molecules (ii) are UV light protection filters. By this are meant organic substances which are able to absorb ultraviolet rays and absorb the absorbed energy in the form of longer-wave radiation, e.g. Heat, give it up again. The organic substances may be oil-soluble or water-soluble.

As oil-soluble UV-B filters, for example, the following substances can be used: 3-benzylidene camphor and its derivatives, eg 3- (4-methylbenzylidene) camphor;

4-aminobenzoic acid derivatives, preferably 2-ethylhexyl 4- (dimethylamino) benzoate, 2-octyl 4- (dimethylamino) benzoate and 4- (dimethylamino) benzoic acid ester;

Esters of cinnamic acid, preferably 2-ethylhexyl 4-methoxycinnamate, 4-propyl methoxy cinnamate, isoamyl 4-methoxycinnamate, 4-isoacetyl methoxycinnamate, 2-cyano-3-phenylcinnamic acid 2-ethylhexyl ester (octocrylene);

Esters of salicylic acid, preferably 2-ethylhexyl salicylate, 4-isopropylbenzyl salicylate, homomenthyl salicylate;

Derivatives of benzophenone, preferably 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxy-4'-methylbenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone;

Esters of benzalmalonic acid, preferably di-2-ethylhexyl 4-methoxybenzmalonate;

Triazine derivatives, such as 2,4,6-trianilino- (p-carbo-2'-ethyl-1 ^'-hexyloxy) -1, 3,5-triazine (octyl tyltriazone) and Dioctyl Butamido Triazone (Uvasorb HEB ^®):

Propane-1,3-diones, e.g. 1- (4-tert-butylphenyl) -3- (4'-methoxyphenyl) propane-1,3-dione.

Suitable water-soluble substances are:

2-phenylbenzimidazole-5-sulfonic acid and its alkali, alkaline earth, ammonium, alkylammonium, alkanolammonium and glucammonium salts;

Sulfonic acid derivatives of benzophenones, preferably 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid and its salts;

Sulfonic acid derivatives of the 3-benzylidene camphor, e.g. 4- (2-Oxo-3-bornylidenemethyl) benzenesulfonic acid and 2-methyl-5- (2-oxo-3-bomylidene) -sulfonic acid and its salts.

Particularly preferred is the use of esters of cinnamic acid, preferably 2-ethylhexyl A-methoxycinnamate, isopentyl 4-methoxycinnamate, 2-ethylhexyl 2-cyano-3-phenylcinnamate (octocrylene). Furthermore, the use of derivatives of benzophenone, in particular 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxy-4 ^x -methylbenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone and the use of propane-1, 3-diones, such as 1- (4-tert-butylphenyl) -3- (4-methethoxyphenyl) propane-1,3-dione.

Typical UV-A filters are:

Derivatives of benzoylmethane, such as 1- (4'-tert-butylphenyl) -3- (4'-methoxyphenyl) propane-1,3-dione, 4-tert-butyl-4'-methoxydibenzoylmethane or 1-phenyl-3 - (4'-isopropylphenyl) -propane-1,3-dione;

Amino-hydroxy-substituted derivatives of benzophenones, e.g. N, N-diethylamino-hydroxybenzoyl-n-hexylbenzoate.

Of course, the UV-A and UV-B filters can also be used in mixtures.

Suitable UV filter substances are mentioned in the following table.

In addition to the two aforementioned groups of primary light stabilizers, it is also possible to use secondary light stabilizers of the antioxidant type which interrupt the photochemical reaction chain which is triggered when UV radiation penetrates into the skin. Typical examples of these are superoxide dismutase, catalase, tocopherols (vitamin E), coenzyme Q10, ubiquinones, quinones and ascorbic acid (vitamin C).

Another group are anti-irritants that have an anti-inflammatory effect on UV-damaged skin. Such substances are, for example, bisabolol, phytol and phytantriol.

According to the invention, effector molecules (ii) are also inorganic pigments that stop UV radiation. Preference is given to pigments based on metal oxides and / or other sparingly water-soluble or insoluble metal compounds selected from the group consisting of the oxides of zinc (ZnO), titanium (TiO 2), iron (eg Fe 2 O 3), zirconium (ZrO 2), silicon (SiO 2), Manganese (eg MnO), aluminum (Al2O3), Cers (eg Ce2O3), mixed oxides of the corresponding metals and mixtures of such oxides.

The inorganic pigments may be present in coated form, i. that they are superficially treated. This surface treatment can be, for example, that the pigments are provided in a manner known per se, as described in DE-A-33 14 742, with a thin hydrophobic layer.

Further preferred effector molecules (ii) are vitamins, especially vitamin A and their esters.

By retinoids in the context of the present invention is meant vitamin A alcohol (retinol) and its derivatives such as vitamin A aldehyde (retinal), vitamin A acid (retinoic acid) and vitamin A esters (e.g., retinyl acetate, retinyl propionate and retinyl palmitate). The term retinoic acid encompasses both all-trans retinoic acid and 13-cis retinoic acid. The terms retinol and retinal preferably include all-trans compounds. The preferred retinoid used for the suspensions according to the invention is all-trans-retinol, referred to below as retinol.

Further preferred effector molecules (ii) are vitamins, provitamins and vitamin precursors from groups A, C, E and F, in particular 3,4-didehydroretinol, .beta.-carotene (Provitamin of vitamin A), ascorbic acid (vitamin C), and the palmitic acid esters, glucosides or phosphates of ascorbic acid, tocopherols, in particular α-tocopherol and its esters, for example the acetate, the nicotinate, the phosphate and the succinate; vitamin F, which is understood as meaning essential fatty acids, especially linoleic acid, linolenic acid and arachidonic acid.

The vitamins, provitamins or vitamin precursors of the vitamin B group or derivatives thereof which are preferably to be used according to the invention and the derivatives of 2-furanone include, inter alia:

Vitamin B ₁ , trivial name thiamine, chemical name 3 - [(4'-amino-2'-methyl-5'-pyrimidinyl) methyl] -5- (2-hydroxyethyl) -4-methylthiazolium chloride.

Vitamin B ₂ , common name riboflavin, chemical name 7,8-dimethyl-10- (1-d-ribityl) benzo [g] pteridine-2,4 (3H, 10H) -dione. In free form riboflavin z. As in whey, other riboflavin derivatives can be isolated from bacteria and yeasts. A stereoisomer of riboflavin which is also suitable according to the invention is lyxoflavin which can be isolated from fishmeal or liver and carries a D-arabityl residue instead of D-ribityl.

Vitamin B ₃ . Under this name, the compounds nicotinic acid and nicotinamide (niacinamide) are often performed. According to the invention, the nicotinic acid amide is preferred.

Vitamin B ₅ (pantothenic acid and panthenol). Panthenol is preferably used. Derivatives of panthenol which can be used according to the invention are, in particular, the esters and ethers of panthenol and also cationically derivatized panthenols. In a further preferred embodiment of the invention, it is also possible to use derivatives of 2-furanone in addition to pantothenic acid or panthenol. Particularly preferred derivatives are the commercially available substances dihydro-3-hydroxy-4,4-dimethyl-2 (3H) -furanone with the trivial name pantolactone (Merck), 4 hydroxymethyl-γ-butyrolactone (Merck), 3,3-dimethyl 2-hydroxy-γ-butyrolactone (Aldrich) and 2,5-dihydro-5-methoxy-2-furanone (Merck), expressly including all stereoisomers.

Advantageously, these effector molecule compounds confer on the protein microbeads according to the invention (i) moisturizing and skin-soothing properties.

Vitamin B ₆ , which is understood here not a single substance, but the known under the common names pyridoxine, pyridoxamine and pyridoxal derivatives of 5-hydroxymethyl-2-methylpyridin-3-ols. Vitamin B ₇ (biotin), also known as vitamin H or "skin vitamin". Biotin is (3aS, 4S, 6aR) -2-oxohexahydrothienol [3,4-d] imidazole-4-valeric acid.

Panthenol, pantolactone, nicotinamide and biotin are very particularly preferred according to the invention.

According to the invention, suitable derivatives (salts, esters, sugars, nucleotides, nucleosides, peptides and lipids) of said compounds can be used as effector molecules. As lipophilic, oil-soluble antioxidants from this group, tocopherol and its derivatives, gallic acid esters, flavonoids and carotenoids, and butylhydroxytoluene / anisole are preferred. As water-soluble antioxidants are amino acids, eg. As tyrosine and cysteine and their derivatives and tanning agents, especially those of plant origin are preferred.

More preferred are so-called peroxide decomposed, i. Compounds which are able to decompose peroxides, particularly preferably lipid peroxides. By this are meant organic substances, such as e.g. Pyridine-2-thiol-3-carboxylic acid, 2-methoxy-pyrimidinol-carboxylic acids, 2-methoxy-pyridinecarboxylic acids, 2-dimethylaminopyrimidinolcarboxylic acids, 2-dimethylaminopyridinecarboxylic acids.

Triterpenes, in particular triterpenic acids such as ursolic acid, rosmarinic acid, betulinic acid, boswellic acid and bryonic acid.

Another preferred effector molecule (ii) is lipoic acid and suitable derivatives (salts, esters, sugars, nucleotides, nucleosides, peptides and lipids).

Further preferred effector molecules (ii) are fatty acids, in particular saturated fatty acids which carry an alkyl branching, particularly preferably branched eicosanoic acids, such as 18-methyl-eicosanoic acid.

Further preferred effector molecules (ii) are dyes, for example food dyes, semi-permanent dyes, reactive or oxidation dyes. In the case of the oxidation dyes, it is preferable to link a component as the effector molecule (ii) to the protein microbeads (i) and then to the site of action, i. after application to skin, to couple with the second dye component oxidatively. In the case of oxidation dyes, it is also preferable to carry out the coupling of the color components before the linkage with the protein microbeads (i).

The reactive dyes may furthermore preferably be linked as a component as effector molecule (ii) to the protein microbeads (i) and subsequently applied to the skin. Furthermore, such dyes, as effector molecule (ii) with The protein microbeads (i) are linked by application to skin in decorative cosmetics.

Suitable dyestuffs are all customary hair dyestuffs for the molecules according to the invention. Suitable dyes are those skilled in handbooks of cosmetics such as Schrader, bases and formulations of cosmetics, Hüthig Verlag, Heidelberg, 1989, ISBN 3-7785-1491 -1 known.

Particularly advantageous dyes are those mentioned in the following list. The Color Index Numbers (CIN) are taken from the Rowe Color Index, 3rd Edition, Society of Dyers and Colourists, Bradford, England, 1971.

Also suitable are food dyes as dyes.

Linkage (coupling) of the effector molecules (M) to the protein (i) The effector molecules (N) are linked to protein (i). The compound between (i) and (ii) may be both a covalent bond and be based on ionic or van der Waals interactions or hydrophobic interactions or hydrogen bonds or adsorption.

Any type of coupling, covalent or noncovalent, of the effector molecule (ii) to the microbead-forming protein (i) may be in the dissolved state prior to phase separation. Following the coupling, the formation of microbeads as described in Example 1 is carried out by phase separation.

Alternatively, a coupling of the effector molecule (ii) to the already produced by phase separation protein microbeads (i) or during the phase separation process.

Preferred is a non-covalent coupling of the effector molecule (ii) to the microbead-forming protein (i). This can be based on ionic or van-der Waals interactions or hydrophobic interactions or hydrogen bonds. During the phase separation, the effector molecule is enclosed in the protein microbeads (i) as described in Example 4 or bound to its surface.

In order to non-covalently bind effector molecules (ii) to the microbead-forming protein (i), the effector molecule (ii) and the protein (i) are dissolved in the same solvent to form a common phase. For this purpose, both components can be brought into solution directly by a solvent or a solvent mixture. Alternatively, the effector molecule (ii) may first be dissolved in a solvent other than the microbead-forming protein (i) and subsequently mixed with the protein solution (i) to form a common phase. Pre-dissolving the effector molecule (ii) is particularly advantageous when the effector molecule (ii) and the microbead-forming protein (i) can not be dissolved in the same solvent, e.g. in aqueous protein solutions (i) and hydrophobic effector molecules (ii). Examples of suitable, water-miscible solvents are alcohols such as methanol, ethanol and isopropanol, fluorinated alcohols such as hexafluoropropanol and trifluoroethanol, alkanones such as acetone or sulfoxides such. Dimethylsulfoxide or formamides such as dimethylformamide. Alternatively, the microbead-forming protein (i) may be expressed in fluorinated alcohols, e.g. Hexafluorisopropanol or trifluoroethanol dissolved and the protein solution are subsequently mixed with effector molecules (ii) in organic solvents. Suitable solvents, e.g. can be mixed well with hexafluoroisopropanol u.a. Alcohols such as methanol, ethanol and

Isopropanol, alkanones such as acetone, sulfoxides such as dimethyl sulfoxide, formamides such as Dimethylformamide, haloalkanes such as methylene chloride or other organic solvents such as tetrahydrofuran.

The noncovalent binding of the effector molecule (ii) to the microbead-forming protein (i) takes place during the assembly of the protein (i) into microbeads, the

Assembly as described in Example 1 by induced phase separation into a solid protein phase and a solvent phase can take place. By choosing the

Solvent and the protein concentration, the average diameter of the protein in microbeads can be adjusted to values between 0.1 .mu.m to 100 .mu.m. Following the assembly reaction, the morphology of the microbeads (i) was to be determined by light and electron microscopy methods.

The binding of the effector molecule may be due to hydrophobic interactions, hydrogen bonding, ionic interaction and van der Waals interactions, or a mixture of these intermolecular forces. In this case, the effector molecule can be bound to the surface of the protein microbeads (i), be included in the protein microbeads (i) or else be associated with the protein microbeads (i) in both ways.

The binding of the effector molecule to the protein microbeads (i) can be determined by the depletion of the assembly approach on soluble effector molecules (ii). The concentration of the effector molecules (ii) can be measured by a quantitative analysis of the effector molecule properties. Thus, the binding of colored effector molecules (ii) may be e.g. be analyzed by photometric methods. For example, the staining of the protein microbeads (i) or the decolorization of the assembly mixture is determined by measuring the absorption of the stained effector molecule. These methods can also be used to calculate the loading density of the protein microbeads (i) (effector molecules per protein) and the loading efficiency (% bound effector molecules).

Alternatively to the non-covalent coupling, a covalent linkage of the effector molecule (ii) to the protein microbeads (i) can be carried out as described in Example 6. This can be carried out, for example, via the side chains of the polypeptide sequence of the microbead-forming protein (i), in particular via amino functions or hydroxyl functions or carboxylate functions or thiol functions. Preferred is a linkage via the amino functions of one or more lysine residues, via the carboxylate functions of one or more glutamate or aspartate residues, one or more thiol groups of cysteine residues or via the N-terminal or C-terminal function of the microbead-forming polypeptide (i ). In addition to the amino acid functions occurring in the microbead-forming polypeptide sequence (i), amino acids with suitable functions (eg cysteines, lysines, aspartates, glutamates) may also be added to the sequence or inserted into the sequence, or Amino acids of the microbead-forming polypeptide sequence (i) are substituted by such amino acid functions.

Linkage of the effector molecules (ii) to the microbead-forming protein (i) may be either directly, i. as a covalent linkage of two in (i) and (ii) already existing chemical functions take place, for example, an amino function of (i) is linked to a carboxylate function of (ii) to the acid amide. The linkage can also be via a so-called linker, i. an at least bifunctional molecule that undergoes a function with (i) a bond and is linked to one or more other functions with (ii).

If the effector molecule (ii) also consists of a polypeptide sequence, the linkage of (i) and (ii) can take place as a so-called fusion protein, i. a continuous polypeptide sequence consisting of the two partial sequences (i) and (ii).

It is also possible to incorporate so-called spacer elements between (i) and (ii), for example polypeptide sequences which have a potential cleavage site for a protease, lipase, esterase, phosphatase, hydrolase or oligopeptide and polypeptide sequences which facilitate easy purification of the fusion protein allow, for example, so-called His-tags, ie Oligohistidinreste.

Furthermore, the spacer elements may be composed of alkyl chains, ethylene glycol and polyethylene glycols.

Especially preferred are linker and / or spacer elements which have a potential cleavage site for a protease, lipase, esterase, phosphatase, hydrolase, i. are enzymatically cleavable. Examples of enzymatically cleavable linkers which can be used in the molecules according to the invention are mentioned, for example, in WO 98/01406, to the entire contents of which reference is hereby expressly made.

Particularly preferred are linkers and spacers which are thermally dissociable, photocleavable. Corresponding chemical structures are known to the person skilled in the art and are integrated between the molecular parts (i) and (ii).

The linkage in the case of a non-proteinaceous effector molecule with the protein microbeads (i) is preferably carried out by functionalizable groups (side groups, C- or N-terminus) on the microbead-forming polypeptide (i) having a covalent chemical function of the effector molecule Make contact. Preference is given here to the bond formation via an amino, thiol or hydroxyl function of the microbead-forming polypeptide (i), which can enter into a corresponding amide, thioester or ester bond, for example with a carboxyl function of the effector molecule (ii), if appropriate after activation.

Another preferred linkage of the protein microbeads (i) with an effector molecule (ii) is the use of a tailored linker. Such a linker has two or more so-called anchor groups with which it can link the microbead-forming polypeptide sequence (i) and one or more effector molecules (ii). For example, an anchor group for (i) may be a thiol function by which the linker can form a disulfide bond with a cysteine residue of the microbead-forming polypeptide (i). An anchor group for (ii) may, for example, be a carboxyl function by means of which the linker with a hydroxyl function of the effector molecule (ii) can undergo ester bonding.

The use of such tailored linker allows the exact adaptation of the linkage to the desired effector molecule. In addition, it is thereby possible to link several effector molecules with a microbead-forming polypeptide sequence (i) in a defined manner.

The linker used depends on the functionality to be coupled. Suitable are e.g. Molecules which couple to microbead-forming polypeptides (i) by means of sulfhydryl-reactive groups, e.g. Maleimides, pydridyl disulfides, α-haloacetyls, vinyl sulfones, sulfatoalkyl sulfones (preferably sulfatoethylsulfones) and to effector molecules (ii) by means of

Sulfhydryl-reactive groups (eg maleimides, Pydridyldisulfide, α-haloacetyls, vinylsulfones, sulfatoalkylsulfones (preferably sulfatoethylsulfones) amine-reactive groups (eg, succinimidyl, carbodiimde, hydroxymethyl-phosphine, imido, PFP esters, aldehyde, isothiocyanate, etc.) - sugar or oxidized sugar-reactive groups (eg hydrazides etc.) carboxy-reactive groups (eg amines etc.) hydroxyl-reactive groups (eg isocyanates etc.) thymine-reactive groups (eg psoralen etc.) unselective groups (eg aryl azides etc.) - photoactivatable groups (eg perfluorophenyl azide etc.)

Metal-complexing groups (e.g., EDTA, hexahis, ferritin)

Antibodies and fragments (e.g., single-chain antibodies, F (ab) fragments of

Antibodies, catalytic antibodies). Alternatively, a direct coupling between effector molecules and the protein microbeads (i) can be carried out, for example, by means of carbodiimides, glutaric dialdehyde, the abovementioned or other crosslinkers known to the person skilled in the art.

The covalently or non-covalently coupled to protein microbeads (i) effector molecules (ii) may be active in their bonded form. Alternatively, the effector molecules (ii) coupled to protein microbeads (i) can also be released from the protein microbeads (i) or from their surface.

The release of covalently coupled effector molecules (ii) from the protein microbeads (i) can be achieved by cleavage of specifically introduced cleavable spacers or coupling linkers, e.g. thermally cleavable, photocleavable or enzymatically cleavable, but also by proteolytic degradation (e.g., by proteases) as described in Example 5 or by dissolution of the protein microbeads (i) or by mechanical disruption of the protein microbeads (i).

The release of non-covalently coupled effector molecules (ii) from the protein microbeads (i) can be by desorption in suitable solvents, by the degradation of the microbeads (i) by proteases or by dissolving the protein microbeads (i) or by mechanical destruction of the Protein microbeads (i) take place. Suitable solvents for the desorption are all solvents or solvent mixtures in which the effector molecule (ii) can be dissolved. Solvents that can dissolve the protein microbeads (i) are e.g. fluorinated alcohols such as trifluoroethanol and hexafluoroisopropanol or else solutions of chaotropic salts such as e.g. Urea, guanidinium hydrochloride and guanidinium thiocyanate.

Suitable proteases can be added as technical proteases to a suspension of protein microbeads (i) in a targeted manner or occur naturally at the desired site of action of the effector molecules (ii), e.g. Skin proteases or proteases released by microorganisms.

The rate and kinetics of the release of the effector molecules (ii) can be controlled by the loading density with effector molecules (ii) and the mean size of the microbeads (i).

For the inventive use in cosmetics, the protein microbeads (i) are formulated with customary other active ingredients and auxiliaries used in cosmetics.

The protein microbeads (i) according to the invention are preferably used for skin cosmetics. They allow a high concentration and long duration of action of skin-care or skin-protecting effector substances. Suitable auxiliaries and additives for the production of hair cosmetic, nail cosmetic or skin cosmetic preparations are familiar to the expert and can from manuals of cosmetics, such as Schrader, bases and formulations of cosmetics, Hüthig Verlag, Heidelberg, 1989, ISBN 3-7785-1491-1 , are taken.

The cosmetic agents according to the invention may be skin-cosmetic, nail-cosmetic, hair-cosmetic, dermatological, hygienic or pharmaceutical agents.

The agents according to the invention are preferably in the form of a gel, foam, spray, ointment, cream, emulsion, suspension, lotion, milk or paste. If desired, liposomes or microspheres can also be used.

The cosmetically or pharmaceutically active agents according to the invention may additionally contain cosmetically and / or dermatologically active agents as well as excipients.

The cosmetic compositions according to the invention preferably comprise at least one protein microbead and at least one different constituent selected from cosmetically active ingredients, emulsifiers, surfactants, preservatives, perfume oils, thickeners, hair polymers, hair and skin conditioners, graft polymers, water-soluble or dispersible silicone-containing Polymers, sunscreens, bleaches, gelling agents, conditioners, colorants, tints, tanning agents, dyes, pigments, bodying agents, moisturizers, restoats, collagen, protein hydrolysates, lipids, antioxidants, defoamers, antistatic agents, emollients and emollients. The protein microbeads (i) can also be present in encapsulated form in the cosmetic preparations.

Advantageously, the antioxidants are selected from the group consisting of amino acids (eg glycine, histidine, tyrosine, tryptophan) and their derivatives, imidazolones (eg urocaninic acid) and their derivatives, peptides such as D, L-carnosine, D-carnosine, L Carnosine and its derivatives (eg anserine), carotenoids, carotenes (eg .beta.-carotene, lycopene) and their derivatives, chlorogenic acid and its derivatives, lipoic acid and derivatives thereof (eg dihydrolipoic acid), aurothioglucose, propylthiouracil and other thiols (eg thiorodoxin , Glutathione, cysteine, cystine, cystamine and their glycosyl, N-acetyl, methyl, ethyl, propyl, amyl, butyl, and lauryl, palmitoyl, oleyl, γ-linoleyl, chlorine, lesteryl and glyceryl esters) and their salts, dilauryl thiodipropionate, distearyl thiodipropionate, thiodipropionic acid and derivatives thereof (esters, ethers, peptides, lipids,

Nucleotides, nucleosides and salts) as well as sulfoximine compounds (eg buthionine sulfoximes, homocysteinesulfoximines, buthionine sulfones, penta, hexa, heptathionine sulfo). ximin) in very low tolerated dosages (eg pmol to μmol / kg), furthermore (metal) chelators (eg α-hydroxyfatty acids, palmitic acid, phytic acid, lactoferrin), α-hydroxy acids (eg citric acid, lactic acid, malic acid), humic acid , Bile acids, bile extracts, bilirubin, biliverdin, EDTA and their derivatives, unsaturated fatty acids and their derivatives (eg γ-linolenic acid, linoleic acid, oleic acid), folic acid and its derivatives, ubiquinone and ubiquinol and their derivatives, vitamin C and derivatives thereof ( eg, sodium ascorbate, ascorbyl palmitate, Mg ascorbyl phosphate, ascorbyl acetate), tocopherol and derivatives (eg, vitamin E acetate, tocotrienol), vitamin A and derivatives (vitamin A palmitate), as well as coniferyl benzoate of benzoin, rutinic acid and derivatives thereof, α-glycosyl rutin , Ferulic acid, furfurylideneglucitol, carnosine, butylhydroxytoluene, butylated hydroxyanisole, nordihydroguaiacetic acid, nordihydroguiaretic acid, trihydroxybutyrophenone, uric acid and its derivatives, Mannose and its derivatives, zinc and its derivatives (eg ZnO, ZnSO ₄ ), selenium and its derivatives (eg selenium methionine), stilbenes and their derivatives (eg stilbene oxide, trans-stilbene oxide).

Also advantageous are so-called peroxide decomposers, i. Compounds which are able to decompose peroxides, particularly preferably lipid peroxides. By this are meant organic substances, such as e.g. Pyridine-2-thiol-3-carboxylic acid, 2-methoxy-pyrimidinol-carboxylic acids, 2-methoxy-pyridinecarboxylic acids, 2-dimethylaminopyrimidinolcarboxylic acids, 2-dimethylaminopyridinecarboxylic acids.

Typical thickeners in such formulations are crosslinked polyacrylic acids and their derivatives, polysaccharides and their derivatives, such as xanthan gum, agar-agar, alginates or tyloses, cellulose derivatives, e.g. Carboxymethylcellulose or hydroxycarboxymethylcellulose, fatty alcohols, monoglycerides and fatty acids, polyvinyl alcohol and polyvinylpyrrolidone. Nonionic thickeners are preferably used.

Suitable cosmetically and / or dermatologically active agents are e.g. coloring active substances, skin and hair pigmenting agents, tinting agents, suntanning agents, bleaching agents, keratin-hardening substances, antimicrobial agents, light-filtering active ingredients, repellent active ingredients, hyperemic substances, keratolytic and keratoplasmic substances, antidandruff active ingredients, antiphlogistics, keratinizing substances, antioxidant or as antioxidants Free-radical scavengers active substances, skin-moisturizing or moisturizing substances, moisturizing agents, anti-erythematous or anti-allergic active substances, branched fatty acids such as 18-methyl eicosanoic acid, and mixtures thereof.

Artificial skin tanning agents which are suitable for tanning the skin without natural or artificial UV rays are, for example, dihydroxyacetone, alloxan and walnut shale extract. Suitable keratin-hardening substances are usually Active substances, as used in antiperspirants, such as potassium aluminum sulfate, aluminum hydroxychloride, aluminum lactate, etc.

Antimicrobial agents are used to destroy microorganisms or to inhibit their growth and thus serve both as a preservative and as a deodorizing substance, which reduces the formation or intensity of body odor. These include e.g. customary preservatives known to the person skilled in the art, such as p-hydroxybenzoic acid ester, imidazolidinyl urea, formaldehyde, sorbic acid, benzoic acid, salicylic acid, etc. Such deodorizing substances are known, for example. Zinc ricinoleate, triclosan, undecylenic acid alkylolamides, citric acid triethyl ester, chlorhexidine etc.

Suitable preservatives which are listed below with their E number are to be used advantageously according to the invention.

In addition, according to the invention preservatives which are customary in cosmetics are preservatives dibromodicyanobutane (2-bromo-2-bromomethylglutarodinitrile), 3-iodo-2-propynyl butyl carbamate, 2-bromo-2-nitro-propane-1,3-diol, imidazolidinyl urea, 5 -Chloro-2-methyl-4-isothiazolin-3-one, 2-chloroacetamide, benzalkonium chloride, benzyl alcohol suitable, Formaldehydabspalter. Furthermore, phenylhydroxyalkyl ethers, in particular the compounds known as phenoxyethanol, are suitable as preservatives because of their bactericidal and fungicidal effects on a number of microorganisms.

Other germ-inhibiting agents are also suitable for incorporation into the preparations according to the invention. Advantageous substances are, for example, 2,4,4'-trichloro-2'-hydroxydiphenyl ether (Irgasan), 1, 6-di- (4-chlorphenylbiguanido) - hexane (chlorhexidine), 3,4,4'-trichlorocarbanilide, quaternary ammonium compounds , Clove oil, mint oil, thyme oil, triethyl citrate, farnesol (3,7,1 1-trimethyl-2,6,10-dodecatriene-1-ol) as well as those disclosed in the patent publications DE-37 40 186, DE-39 38 140, DE -42 04 321, DE-42 29 707, DE-43 09 372, DE-44 1 1 664, DE-195 41 967, DE-195 43 695, DE-195 43 696, DE-195 47 160, DE- 196 02 108, DE-196 02 1 10, DE-196 02 1 1 1, DE-196 31 003, DE-196 31 004 and DE-196 34 019 and the patents DE-42 29 737, DE-42 37 081 , DE-43 24 219, DE-44 29 467, DE-44 23 410 and DE-195 16 705 described active ingredients or drug combinations. Also, sodium bicarbonate is advantageous to use. Likewise, antimicrobial polypeptides can also be used.

Suitable light filter active substances are substances which absorb UV rays in the UV-B and / or UV-A range. Suitable UV filters are e.g. 2,4,6-triaryl-1,3,5-triazines in which the aryl groups can each bear at least one substituent, which is preferably selected from hydroxy, alkoxy, especially methoxy, alkoxycarbonyl, especially methoxycarbonyl and ethoxycarbonyl, and mixtures thereof. Also suitable are p-aminobenzoic acid esters, cinnamic acid esters, benzophenones, camphor derivatives and UV-radiation-stopping pigments, such as titanium dioxide, talc and zinc oxide.

Suitable UV filter substances are any UV-A and UV-B filter substances. For example:

38 1, 1 - [(2,2 ^{'-Dimethylpropoxy)} carbonyl] -4,4-diphenyl-1, 3-butadiene 363602-15-7

The cosmetic and dermatological preparations according to the invention may advantageously also contain UV-blocking inorganic pigments based on metal oxides and / or other sparingly soluble or insoluble metal compounds selected from the group of the oxides of zinc (ZnO), titanium (TiO ₂ ), iron ( eg Fe ₂ O ₃ ), zirconium (ZrO ₂ ), silicon (SiO ₂ ), manganese (eg MnO), aluminum (Al ₂ O ₃ ), cerium (eg Ce ₂ O ₃ ), mixed oxides of the corresponding metals and mixtures thereof Contain oxides.

Suitable repellent agents are compounds capable of preventing or repelling certain animals, particularly insects, from humans. This includes e.g. 2-ethyl-1,3-hexanediol, N, N-diethyl-m-toluamide, etc. Suitable hyperemic substances which stimulate the perfusion of the skin are e.g. essential oils such as mountain pine extract, lavender extract, rosemary extract, juniper berry extract, horse chestnut extract, birch leaf extract, hay flower extract, ethyl acetate, camphor, menthol, peppermint oil, rosemary extract, eucalyptus oil, etc. Suitable keratolytic and keratoplastic substances are e.g. Salicylic acid, calcium thioglycolate, thioglycolic acid and its salts, sulfur, etc. Suitable anti-dandruff agents are e.g. Sulfur, sulfur polyethylene glycol sorbitan monooleate, sulfur ricinol polyethoxylate, zinc pyrithione, aluminum pyrithione, etc. Suitable antiphlogistic agents which counteract skin irritation are e.g. Allantoin, bisabolol, dragosantol, chamomile extract, panthenol, etc.

The cosmetic agents according to the invention may contain as cosmetic and / or pharmaceutical active ingredient (as well as optionally as excipient) at least one cosmetically or pharmaceutically acceptable polymer. These include, in general, cationic, amphoteric and neutral polymers.

Suitable polymers are, for example, cationic polymers with the name polyquaternium according to INCI, for example copolymers of vinylpyrrolidone / N-vinylimidazolium salts (Luviquat FC, Luviquat HM, Luviquat MS, Luviquat®, Care), copolymers of N-vinylpyrrolidone / dimethylaminoethyl methacrylate, quaternized with Diethyl sulfate (Luviquat PQ 11), copolymers of N-vinylcaprolactam / N-vinylpyrrolidone / N-vinylimidazolium salts (Luviquat E Hold), cationic cellulose derivatives (polyquaternium-4 and -10), acrylamidocopolymers (Polyquaternium-7) and chitosan. Suitable cationic (quaternized) polymers are also merquat (polymer based on dimethyldiallyl ammonium chloride), gafquat (quaternary polymers formed by reaction of polyvinylpyrrolidone with quaternary ammonium compounds), polymer JR (hydroxyethylcellulose with cationic groups) and cationic polymers on a vegetable basis, eg guar polymers , like the Jaguar brands of Rhodia.

Further suitable polymers are also neutral polymers, such as polyvinylpyrrolidones, copolymers of N-vinylpyrrolidone and vinyl acetate and / or vinyl propionate, polysiloxanes, polyvinylcaprolactam and other copolymers with N-vinylpyrrolidone, polyethylenimines and their salts, polyvinylamines and their salts, cellulose derivatives, Polyasparaginic acid salts and derivatives. These include, for example, Luviflex 0 Swing (partially saponified copolymer of polyvinyl acetate and polyethylene glycol, BASF).

Suitable polymers are also nonionic, water-soluble or water-dispersible polymers or oligomers, such as polyvinylcaprolactam, e.g. Luviskol 0 Plus (BASF), or polyvinylpyrrolidone and their copolymers, in particular with vinyl esters, such as vinyl acetate, e.g. Luviskol 0 VA 37 (BASF), polyamides, e.g. based on itaconic acid and aliphatic diamines, e.g. in DE-A-43 33 238 are described.

Suitable polymers are also amphoteric or zwitterionic polymers, such as those available under the names Amphomer (National Starch) octylacrylamide / methyl methacrylate / tert-butylaminoethyl methacrylate hydroxypropyl methacrylate copolymers and zwitterionic polymers, as described for example in German patent applications DE39 29 973, DE 21 50 557, DE 28 17 369 and DE 3708 451 are disclosed. Acrylamidopropyl trimethylammonium chloride / acrylic acid or. -Methacrylsäure-

Copolymers and their alkali metal and ammonium salts are preferred zwitterionic polymers. Further suitable zwitterionic polymers are methacroylethylbetaine / methacrylate copolymers, which are commercially available under the name Amersette (AMERCHOL), and copolymers of hydroxyethyl methacrylate, methyl methacrylate, N, N-dimethylaminoethyl methacrylate and acrylic acid (Jordapon (D)).

Suitable polymers are also nonionic, siloxane-containing, water-soluble or -dispersible polymers, e.g. Polyether siloxanes, such as Tegopren 0 (Goldschmidt) or Besi & commat (Wacker).

The formulation base of cosmetic agents according to the invention preferably contains cosmetically and / or pharmaceutically acceptable excipients. Pharmaceutically acceptable excipients which are known in the field of pharmacy, food technology and related fields, in particular those listed in relevant pharmacopoeias (eg DAB Ph. Eur. BP NF) and other excipients whose properties do not preclude physiological application. Suitable auxiliaries may be: lubricants, wetting agents, emulsifying and suspending agents, preserving agents, antioxidants, anti-irritants, chelating agents, emulsion stabilizers, film formers, gelling agents, odor masking agents, resins, hydrocolloids, solvents, solubilizers, neutralizing agents, permeation accelerators, pigments, quaternary ammonium compounds, Rest grease and superfatting agents, ointment, cream or oil bases, silicone derivatives, stabilizers, sterilants, blowing agents, drying agents, opacifiers, thickeners, waxes, softeners, white oil. A related embodiment is based on professional knowledge, as shown for example in Fiedler, HP Lexicon of excipients for pharmacy, cosmetics and related fields, 4th ed., Aulendorf: ECV Editio Kantor Verlag, 1996.

To prepare the dermatological agents of the invention, the active ingredients may be mixed or diluted with a suitable excipient (excipient). Excipients may be solid, semi-solid or liquid materials which may serve as a vehicle, carrier or medium for the active ingredient. If desired, the admixing of further auxiliaries takes place in the manner known to the person skilled in the art. Furthermore, the polymers and dispersions are suitable as auxiliaries in pharmacy, preferably as or in coating agent (s) or binder (s) for solid dosage forms. They can also be used in creams and as tablet coatings and tablet binders.

According to a preferred embodiment, the agents according to the invention are a skin cleanser.

Preferred skin cleansing agents are soaps of liquid to gelatinous consistency, such as transparent soaps, luxury soaps, deep soaps, cream soaps, baby soaps, skin soaps, abrasive soaps and syndets, pasty soaps, greases and washes, exfoliating soaps, moisturizing wipes, liquid washing, showering and bathing preparations such as washing lotions. Shower baths and gels, bubble baths, oil baths and scrub preparations, shaving foams, lotions and creams.

According to a further preferred embodiment, the agents according to the invention are cosmetic agents for the care and protection of the skin and hair, nail care preparations or preparations for decorative cosmetics.

Suitable skin-cosmetic agents are, for example, face lotions, face masks, deodorizers and other cosmetic lotions. Means for use in decorative cosmetics include, for example, masking pens, theatrical paints, mascara and eyeshades, lipsticks, kohl pencils, eyeliner, rouges, powders and eyebrow pencils. In addition, the dermatological agents according to the invention can be used in nose strips for

Pore cleansing, in anti-acne products, repellents, shaving agents, after- and pre-shave care products, after-sun care products, hair removal products, hair coloring agents, intimate care products, foot care products as well as in baby care.

The skin care compositions according to the invention are in particular W / O or O / W skin creams, day and night creams, eye creams, face creams, anti-wrinkle creams, sunscreen creams, moisturizing creams, bleaching creams, self-tanning creams, vitamin creams, skin lotions, skin lotions and moisturizing lotions ,

Skin cosmetic and dermatological compositions based on the previously described protein microbeads (i) show advantageous effects. Among other things, the protein microbeads (i) can contribute to the moisturization and conditioning of the skin and to the improvement of the skin feel. The protein microbeads (i) can also act as thickeners in the formulations. By adding the protein microbeads (i) according to the invention, a significant improvement in skin compatibility can be achieved in certain formulations.

Skin cosmetic and dermatological compositions preferably contain at least one protein microbeads (i) in a proportion of about 0.001 to 30% by weight, preferably 0.01 to 20% by weight, very particularly preferably 0.1 to 12% by weight. , based on the total weight of the agent.

Especially light stabilizers based on the protein microbeads (i) have the property to increase the residence time of the UV-absorbing ingredients in comparison to conventional aids such as polyvinylpyrrolidone.

Depending on the field of application, the compositions according to the invention may be in a form suitable for skin care, e.g. as a cream, foam, gel, pen, mousse, milk, spray (pump spray or propellant spray) or lotion can be applied.

In addition to the protein microbeads (i) and suitable carriers, the skin cosmetic preparations may contain other active ingredients and excipients customary in skin cosmetics, as described above. These preferably include emulsifiers, preservatives, perfume oils, cosmetic active ingredients such as phytantriol, vitamins A, E and C, retinol, bisabolol, panthenol, light stabilizers, bleaching agents, colorants, tinting agents, tanning agents, collagen, enzymes, protein hydrolysates, stabilizers, pH regulators , Dyes, salts, thickeners, gelling agents, bodying agents, silicones, humectants, moisturizers and other common additives. Preferred oil and fat components of the skin-cosmetic and dermatological agents are the aforementioned mineral and synthetic oils, such as paraffins, silicone oils and aliphatic hydrocarbons having more than 8 carbon atoms, animal and vegetable oils, such as sunflower oil, coconut oil, avocado oil, olive oil, lanolin, or waxes, fatty acids, fatty acid esters such as triglycerides of C6-C30 fatty acids, wax esters such as jojoba oil, fatty alcohols, petrolatum, hydrogenated lanolin and acetylated lanolin, and mixtures thereof.

The protein microbeads according to the invention (i) can also be mixed with conventional polymers if special properties are to be set.

For setting certain properties, e.g. Improving the feeling of touch, the spreading behavior, the water resistance and / or the binding of active ingredients and auxiliaries, such as pigments, may additionally contain skin-cosmetic and dermatological preparations and also conditioning substances based on silicone compounds.

Suitable silicone compounds are, for example, polyalkylsiloxanes, polyarylsiloxanes, polyarylalkylsiloxanes, polyethersiloxanes or silicone resins.

The preparation of the cosmetic or dermatological preparations is carried out by customary methods known to the person skilled in the art.

The cosmetic and dermatological agents are preferably in the form of emulsions, in particular as water-in-oil (W / O) or oil-in-water (O / W) emulsions.

But it is also possible to choose other types of formulations, for example, gels, oils, oil gels, multiple emulsions, for example in the form of W / O / W or O / W / O emulsions, anhydrous ointments or ointment bases, etc. Also emulsifier-free formulations such as hydrodispersions, hydrogels or a Pickering emulsion are advantageous embodiments.

Emulsions are prepared by known methods. The emulsions contain, in addition to at least one protein microbead (i), as a rule, customary constituents, such as fatty alcohols, fatty acid esters and especially fatty acid triglycerides, fatty acids, lanolin and derivatives thereof, natural or synthetic oils or waxes and emulsifiers in the presence of water. The selection of the emulsion type-specific additives and the preparation of suitable emulsions is described, for example, in Schrader, Grundlagen und Rezepturen der Kosmetika, Huthig Buch Verlag, Heidelberg, 2nd edition, 1989, third part, to which reference is hereby expressly made. A suitable emulsion as W / O emulsion, for example for a skin cream, etc., generally contains an aqueous phase which is emulsified by means of a suitable emulsifier system in an oil or fat phase. To provide the aqueous phase, a polyelectrolyte complex can be used.

Preferred fat components which may be included in the fat phase of the emulsions are: hydrocarbon oils such as paraffin oil, purcellin oil, perhydrosqualene and solutions of microcrystalline waxes in these oils; animal or vegetable oils, such as sweet almond oil, avocado oil, calophilum oil, lanolin and derivatives thereof, castor oil, seed oil, olive oil, jojoba oil, karite oil, hoplostethus oil, mineral oils, whose onset of distillation under atmospheric pressure at about 250 ⁹ C and their Distillation end point at 410 ⁹ C, such as Vaselineöl, esters of saturated or unsaturated fatty acids, such as alkyl myristates, for example, i-propyl, butyl or Cetylmyristat, hexadecyl, ethylene or i-propyl palmitate, octanoic or Decansäuretriglyceride and Cetylricinoleat.

The fat phase may also contain other oil-soluble silicone oils such as dimethylpolysiloxane, methylphenylpolysiloxane and the silicone glycol copolymer, fatty acids and fatty alcohols.

In addition to the protein microbeads (i), waxes may also be used, e.g. Carnauba wax, candililla wax, beeswax, microcrystalline wax, ozokerite wax and Ca, Mg and Al oleates, myristates, linoleates and stearates.

Furthermore, an emulsion of the invention may be present as O / W emulsion. Such an emulsion usually contains an oil phase, emulsifiers that stabilize the oil phase in the water phase, and an aqueous phase that is usually thickened. Suitable emulsifiers are preferably O / W emulsifiers, such as polyglycerol esters, sorbitan esters or partially esterified glycerides into consideration.

According to a further preferred embodiment, the agents according to the invention are a shower gel, a shampoo formulation or a bathing preparation.

Such formulations contain at least one protein microbead (i) and usually anionic surfactants as base surfactants and amphoteric and / or nonionic surfactants as cosurfactants. Other suitable active ingredients and / or auxiliaries are generally selected from lipids, perfume oils, dyes, organic acids, preservatives and antioxidants, as well as thickeners / gelling agents, skin conditioners and humectants. These formulations preferably contain from 2 to 50% by weight, preferably from 5 to 40% by weight, particularly preferably from 8 to 30% by weight of surfactants, based on the total weight of the formulation.

In the washing, shower and bath preparations all anionic, neutral, amphoteric or cationic surfactants commonly used in personal care products can be used.

Suitable anionic surfactants are, for example, alkyl sulfates, alkyl ether sulfates, alkyl sulfonates, alkylaryl sulfonates, alkyl succinates, alkyl sulfosuccinates, N-alkoyl sarcosylates, acyl taurates, acyl isothionates, alkyl phosphates, alkyl ether phosphates, alkyl ether carboxylates, alpha-olefin sulfonates, especially the alkali and alkaline earth metal salts, e.g.

Sodium, potassium, magnesium, calcium, as well as ammonium and triethanolamine salts.

The alkyl ether sulfates, alkyl ether phosphates and alkyl ether carboxylates can have between 1 to 10 ethylene oxide or propylene oxide units, preferably 1 to 3 ethylene oxide units in the molecule.

These include e.g. Sodium lauryl sulfate, ammonium tauryl sulfate, sodium lauryl ether sulfate, ammonium lauryl ether sulfate, sodium lauryl sarcosinate, sodium oleyl succinate, ammonium lauryl sulfosuccinate, sodium dodecyl benzene sulfonate, triethanolamine dodecyl benzene sulfonate.

Suitable amphoteric surfactants are e.g. Alkylbetaines, alkylamidopropylbetaines, alkylsulfobetaines, alkylglycinates, alkylcarboxyglycinates, alkylamphoacetates or -propionates, alkylamphodiacetates or -dipropionates.

For example, cocodimethylsulfopropyl betaine, lauryl betaine, cocamidopropyl betaine or sodium cocamphopropionate can be used.

Suitable nonionic surfactants are, for example, the reaction products of aliphatic alcohols or alkylphenols having 6 to 20 C atoms in the alkyl chain, which may be linear or branched, with ethylene oxide and / or propylene oxide. The amount of alkylene oxide is about 6 to 60 moles per mole of alcohol. Also suitable are alkylamine oxides, mono- or dialkylalkanolamides, fatty acid esters of polyethylene glycols, ethoxylated fatty acid amides, alkylpolyglycosides or sorbitan ether esters.

In addition, the washing, showering and bathing preparations may contain customary cationic surfactants, for example quaternary ammonium compounds, for example cetyltrimethylammonium chloride. Furthermore, the shower gel / shampoo formulations may contain thickeners, such as, for example, common salt, PEG-55, propylene glycol oleate, PEG-120-methyl glucose dioleate and others, as well as preservatives, other active ingredients and auxiliaries and water.

According to a further preferred embodiment, the agents according to the invention are a hair treatment agent.

Hair treatment agents according to the invention preferably contain at least protein in microbeads (i) in an amount in the range of about 0.01 to 30 wt .-%, preferably 0.5 to 20 wt .-%, based on the total weight of the composition.

Preferably, the hair treatment compositions of the present invention are in the form of a mousse, hair mousse, hair gel, shampoo, hair spray, hair mousse, top fluid, perming, hair dyeing and bleaching or hot oil treatments. Depending on the field of application, the hair cosmetic preparations can be applied as (aerosol) spray, (aerosol) foam, gel, gel spray, cream, lotion or wax. Hairsprays include both aerosol sprays and pump sprays without propellant gas. Hair foams include both aerosol foams and pump foams without propellant gas. Hair sprays and hair foams preferably comprise predominantly or exclusively water-soluble or water-dispersible components. If the compounds used in the hair sprays and hair foams according to the invention are water-dispersible, they can be used in the form of aqueous microdispersions with particle diameters of usually from 1 to 350 nm, preferably from 1 to 250 nm. The solids contents of these preparations are usually in a range of about 0.5 to 20 wt .-%. As a rule, these microdispersions do not require emulsifiers or surfactants for their stabilization.

In a preferred embodiment, the hair cosmetic formulations of the invention comprise a) from 0.01 to 30% by weight of at least one protein microbead (i) b) from 20 to 99.95% by weight of water and / or alcohol, c) 0 up to 50% by weight of at least one propellant gas, d) 0 to 5% by weight of at least one emulsifier, e) 0 to 3% by weight of at least one thickener and up to 25% by weight of further constituents.

By alcohol are meant all alcohols customary in cosmetics, e.g. Ethanol, isopropanol, n-propanol.

Further constituents are understood to include the additives customary in cosmetics, for example blowing agents, defoamers, surface-active compounds, ie surfactants, emulsifiers, foaming agents and solubilizers. The surface-active compounds used can be anionic, cationic, amphoteric or neutral. Other common ingredients may also be eg preservatives, perfume oils, Opacifiers, active ingredients, UV filters, care agents such as panthenol, collagen, vitamins, protein hydrolysates, alpha and beta hydroxycarboxylic acids, stabilizers, pH regulators, dyes, viscosity regulators, gelling agents, salts, humectants, moisturizers, complexing agents and other conventional additives ,

Furthermore, this includes all known in cosmetics styling and conditioner polymers, which can be used in combination with the protein microbeads of the invention (i), if very special properties are to be set.

Suitable conventional hair cosmetic polymers include, for example, the abovementioned cationic, anionic, neutral, nonionic and amphoteric polymers, to which reference is hereby made.

To adjust certain properties, the preparations may additionally contain conditioning substances based on silicone compounds. Suitable silicone compounds are, for example, polyalkylsiloxanes, polyarylsiloxanes, polyarylalkylsiloxanes, polyethersiloxanes, silicone resins or dimethicone copolyols (CTFA) and amino-functional silicone compounds such as amodimethicones (CTFA).

The polymers according to the invention are suitable in particular as setting agents in hairstyling preparations, in particular hairsprays (aerosol sprays and pump sprays without propellant gas) and hair foams (aerosol foams and pump foams without propellant gas).

In a preferred embodiment, spray preparations contain a) 0.01 to 30% by weight of at least one protein microbead (i), b) 20 to 99.9% by weight of water and / or alcohol, c) 0 to 70 Wt .-% of at least one blowing agent, d) 0 to 20 wt .-% further ingredients.

Blowing agents are the blowing agents commonly used for hairsprays or aerosol foams. Preference is given to mixtures of propane / butane, pentane, dimethyl ether, 1,1-difluoroethane (HFC-152a), carbon dioxide, nitrogen or compressed air.

A preferred formulation for aerosol hair foams according to the invention comprises a) from 0.01 to 30% by weight of at least one protein microbead (i), b) from 55 to 99.8% by weight of water and / or alcohol, c) from 5 to 20% by weight % of a blowing agent, d) 0.1 to 5% by weight of an emulsifier, e) 0 to 10% by weight of further constituents.

As emulsifiers all emulsifiers commonly used in hair foams can be used. Suitable emulsifiers may be nonionic, cationic or anionic or amphoteric. Examples of nonionic emulsifiers (INCI nomenclature) are Laurethe, for example Laureth-4; Cetethees, for example cetheth-1, polyethylene glycol cetyl ethers, ceteareses, for example cethethreeth-25, polyglycol fatty acid glycerides, hydroxylated lecithin, lactyl esters of fatty acids, alkylpolyglycosides.

Examples of cationic emulsifiers are cetyldimethyl-2-hydroxyethylammonium dihydrogenphosphate, cetyltrimonium chloride, cetyltrimmonium bromide, cocotrimonium methylsulfate, quaternium-1 to x (INCI).

Anionic emulsifiers may, for example, be selected from the group of alkyl sulfates, alkyl ether sulfates, alkyl sulfonates, alkylaryl sulfonates, alkyl succinates, alkyl sulfosuccinates, N-alkoyl sarcosinates, acyl taurates, acyl isethionates, alkyl phosphates, alkyl ether phosphates, alkyl ether carboxylates, alpha olefin sulfonates, especially the alkali and alkaline earth metal salts, e.g. Sodium, potassium, magnesium, calcium, as well as ammonium and triethanolamine salts. The alkyl ether sulfates, alkyl ether phosphates and alkyl ether carboxylates can have between 1 to 10 ethylene oxide or propylene oxide units, preferably 1 to 3 ethylene oxide units in the molecule.

A preparation suitable for styling gels according to the invention can be composed, for example, as follows: a) 0.01 to 30% by weight of at least one protein

Microbeads (i), b) 80 to 99.85% by weight of water and / or alcohol, c) 0 to 3% by weight, preferably 0.05 to 2% by weight, of a gelling agent, d) 0 to 20% by weight of other ingredients. The use of gelling agents may be advantageous for adjusting specific theological or other application properties of the gels. As gel formers, all gel formers customary in cosmetics can be used. These include lightly crosslinked polyacrylic acid, for example carbomer (INCI), cellulose derivatives, e.g. Hydroxypropyl cellulose, hydroxyethyl cellulose, cationic modified celluloses, polysaccharides, e.g. Xanthan gum, caprylic / capric triglyceride, sodium acrylate copolymers, Polyquaternium-32 (and) Paraffinum Liquidum (INCI), sodium acrylate copolymers (and) Paraffinum Liquidum (and) PPG-1 trideceth-6, acrylamidopropyltrimonium chloride / acrylamide copolymers, Steareth-10-allyl ethers, acrylate copolymers, polyquaternium-37 (and) paraffin liquidum (and) PPG-1 trideceth-6, polyquaternium 37 (and) propylene glycol dicaprate dicaprylate (and) PPG-1 trideceth-6, polyquaternium 7, Polyquaternium-44.

The protein microbeads (i) according to the invention can be used as conditioning agents in cosmetic preparations.

A preparation containing the protein microbeads (i) according to the invention can preferably be used in shampoo formulations as a setting and / or conditioning agent. Preferred shampoo formulations contain a) 0.01 to 30% by weight at least one protein microbead (i), b) 25 to 94.95% by weight of water, c) 5 to 50% by weight of surfactants, c) 0 to 5% by weight of a further conditioning agent, d) 0 to 10% by weight of other cosmetic ingredients.

In the shampoo formulations all anionic, neutral, amphoteric or cationic surfactants commonly used in shampoos can be used.

Suitable anionic surfactants include, for example, alkyl sulfates, alkyl ether sulfates, alkyl sulfonates, alkylaryl sulfonates, alkyl succinates, alkyl sulfosuccinates, N-alkoxy sarcosinates, acyl taurates, acyl isothionates, alkyl phosphates, alkyl ether phosphates, alkyl ether carboxylates, alpha olefin sulfonates, especially the alkali and alkaline earth metal salts, e.g. Sodium, potassium, magnesium, calcium, and ammonium and triethanolamine salts. The alkyl ether sulfates, alkyl ether phosphates and alkyl ether carboxylates can have between 1 to 10 ethylene oxide or propylene oxide units, preferably 1 to 3 ethylene oxide units in the molecule.

Suitable examples are sodium lauryl sulfate, ammonium lauryl sulfate, sodium lauryl sulfate, ammonium lauryl ether sulfate, sodium lauroyl sarcosinate, sodium oleyl succinate, ammonium lauryl sulfosuccinate, sodium dodecylbenzenesulfonate, triethanolamine dodecylbenzenesulfonate.

Suitable amphoteric surfactants are, for example, alkylbetaines, alkylamidopropylbetaines, alkylsulfobetaines, alkylglycinates, alkylcarboxyglycinates, alkylamphoacetates or -propionates, alkylamphodiacetates or -dipropionates.

Suitable nonionic surfactants are, for example, the reaction products of aliphatic alcohols or alkylphenols having 6 to 20 C atoms in the alkyl chain, which may be linear or branched, with ethylene oxide and / or propylene oxide. The amount of alkylene oxide is about 6 to 60 moles per mole of alcohol. Also suitable are alkylamine oxides, mono- or dialkylalkanolamides, fatty acid esters of polyethylene glycols, alkylpolyglycosides or sorbitan ether esters.

In addition, the shampoo formulations may contain conventional cationic surfactants, e.g. quaternary ammonium compounds, for example cetyltrimethylammonium chloride.

Conventional conditioning agents in combination with the protein microbeads (i) can be used in the shampoo formulations to achieve certain effects. These include, for example, the aforementioned cationic polymers with the name Polyquaternium according to INCI, in particular copolymers of vinylpyrrolidone / N-vinylimidazolium salts (Luviquat FC, Luviquat & commat, HM, Luviquat MS, Luviquat Care), copolymers of N-vinylpyrrolidone / dimethylaminoethyl methacrylate, quaternized with diethyl sulfate ( Luviquat D PQ 11), copolymers of N-vinylcaprolactam / N-

Vinylpyrrolidone / N-vinylimidazolium salts (Luviquat D Hold), cationic cellulose derivatives (Polyquaternium-4 and -10), acrylamide copolymers (Polyquaternium-7). Furthermore, protein hydrolysates can be used, as well as conditioning substances based on silicone compounds, for example polyalkylsiloxanes, polyarylsiloxanes, polyarylalkylsiloxanes, polyethersiloxanes or silicone resins. Other suitable silicone compounds are dimethicone copolyols (CTFA) and amino-functional silicone compounds such as amodimethicones (CTFA). Furthermore, cationic guar derivatives such as guar hydroxypropyltrimonium chloride (INCI) can be used.

Experimental part

example 1

Method for producing globular protein microbeads from the silk protein C16 in solution

An aqueous C16 solution is prepared. For this purpose, lyophilized C16 is dissolved in 6 M guanidinium thiocyanate (GdmSCN) to a final concentration of 0.1-10 mg / ml. Subsequently, the GdmSCN is removed by dialysis against 5 mM potassium phosphate pH 8.0.

The formation of β-sheet-rich C16 microbeads is induced at room temperature by the rapid addition of 500 mM potassium phosphate pH 8.0 and 800 mM ammonium sulfate (final concentration) to the protein solution, followed by brief mixing (e.g., panning of the reaction vessel). The mean particle diameter depends on the protein concentration used and can be varied between 0.5 μm and 15 μm. The particles are then washed with water and lyophilized. The success of microbead formation is verified by scanning electron microscopy.

Example 2: Determination of the Thermal Stability of C16 Microbeads by Thermogravimetric Analysis (TGA)

The thermal stability of C16 microbeads was determined using the apparatus "Thermogravimetric Analyzer TGA 7" from Perkin-Elmer, using aluminum sample containers having a volume of 40 μl, and 4 l / h of nitrogen as purge gas for the balance. 6 l / h of nitrogen or air (depending on the measurement) was used as purge gas for the test room 1. The sample was heated from 30 to 500 ° C. at a heating rate of 5 K / min. During the measurement, the sample weight and the oven temperature became Figure 1 shows the variation of the C16 microbead sample weight over the temperature It can be clearly seen that the majority of the analyzed C16 microbeads are stable up to temperatures of at least 250 ° C. Only then is a significant mass loss evident, which is due to the decomposition of the sample.

Example 3:

Water uptake of C16 microbeads

C16 microbeadscrobeads can absorb or release water from the air and thus serve as a moisture-regulating substance in cosmetic applications.

To demonstrate this, 0.4 g - 0.5 g of C16 microbeads previously stored at -20 ° C were vacuum dried for 16 hours. By this treatment, the microbeads lost 12% of their weight (in terms of dry weight). Subsequent storage at room temperature and 100% humidity resulted in a slow weight gain of 25% within 19 days (see Figure 2). By re-drying in vacuo, the original dry weight was reached again.

Example 4:

Formulation of canthaxanthin

To show that the C16 microbeads are suitable as carriers and formulation auxiliaries for effector molecules, canthaxanthin was bound to C16 microbeads as an example.

For this purpose, 500 .mu.l of a solution of 20 mg / ml C16 in 5 mM potassium phosphate (pH 8.0) were mixed with 50 .mu.l of a solution of 2 mg / ml canthaxanthin in DMSO after the insoluble microcrystals were removed by centrifugation. Following was the Formation of C16 microbeads induced by addition of 500 μl of a 1 M potassium phosphate solution (pH 8.0).

During formation of the C16 microbeads, the canthaxanthin was quantitatively removed from the solution, as demonstrated by determining the absorbance in the supernatant after centrifuging the C16 microbeads (Figure 3). The centrifuged C16 microbeads appeared clearly pink-violet colored. After lyophilization, the loaded C16 microbeads were analyzed by electron microscopy. In the electron micrograph, the loaded C16 microbeads did not differ from the unloaded control prepared under the same conditions, indicating that the C16 microbeads and the canthaxanthin form a common solid phase (Figure 4).

To test how strong the binding of canthaxanthin was to the C16 microbeads, the loaded microbeads were washed with 5 mM potassium phosphate (pH 8.0), 5 mM potassium phosphate (pH 8.0) + 5% DMSO and pure DMSO. For this purpose, the C16 microbeads were incubated with 1 ml of the solutions for about 1 min. Subsequently, centrifugation was carried out and the canthaxanthin content in the supernatant was measured by determining the extinction. While no canthaxanthin could be solubilized by washing with and with only 5% DMSO, the majority of the bound canthaxanthin went into solution by a single wash with pure DMSO (Figure 5). The canthaxanthin can no longer be washed out by the conditions under which it was bound to the microbeads (5% DMSO), which suggests a strong association with the microbeads.

As a control, 500 μl of a solution of 5 mM potassium phosphate (pH 8.0) were mixed with 50 μl of the canthaxanthin solution in DMSO. In the absence of C16, the solution remained clear even after addition of 500 μl of a 1 M potassium phosphate solution (pH 8.0). The canthaxanthin was unable under the conditions of the assembly to form a solid phase alone.

In order to test whether the canthaxanthin is adsorbed essentially to the surface of the C16 microbeads or whether canthaxanthin is also included in the C16 microbeads, 500 μl of a solution of 5 mM potassium phosphate (pH 8.0) with 50 μl The Canthaxanthinlösung mixed in DMSO and then added 10 mg of uncharged, white C16 microbeads. To the suspension was then added 500 μl of the 1 M potassium phosphate solution (pH 8.0). After centrifugation of the C16 microbeads, the majority of the canthaxanthin used was found in the supernatant, only a small portion was bound to the microbeads (FIG. 3), which was also evident from the slightly violet coloration of the C16 microbeads. Was again tested by washing with 1 ml of a solution of 5% DMSO in 5 mM potassium phosphate (pH 8.0), how strong is the association of canthaxanthin to the C16 microbeads. In contrast to the C16 microbeads, which were formed in the presence of canthaxanthin, all bound canthaxanthin could now be washed out (Fig. 6), indicating a much weaker association of canthaxanthin with existing C16 microbeads. Overall, the binding of canthaxanthin to the C16 microbeads formed in the presence of canthaxanthin differs from the adsorption on existing C16 microbeads, suggesting that canthaxanthin is included in the microbeads during assem- bly.

Example 5:

Release of canthaxanthin from C16 microbeads

In addition to washing out canthaxanthin by solvents, e.g. DMSO (Figure 5), the release can also be done by degradation of the C16 microbeads. In order to demonstrate the degradation of the C16 microbeads by proteases, 150 μl of C16 in 5 mM potassium phosphate (pH 8.0) were mixed with 150 μl of a saturated solution of canthaxanthin in DMSO in a total of two batches (FIGS. 7, a and b) mixed. Subsequently, 700 μl of a 1 M potassium phosphate solution (pH 8.0) was added to induce formation of the C16 microbeads. As a control, 150 μl of a solution of 5 mM potassium phosphate (pH 8.0) were mixed with 150 μl of a saturated solution of canthaxanthin in DMSO and 700 μl of a 1 M potassium phosphate solution (pH 8.0) (control without C16). All batches were incubated for 1.5 hours at RT and then centrifuged off. While in the batches with C16 orange-purple colored microbeads were formed, no precipitation was observed during the control.

The supernatants were removed and the canthaxanthin-loaded C16 microbeads were taken up in 1 ml of a 5 mM potassium phosphate solution (pH 8.0). The canthaxanthin content in the supernatants was determined photometrically using the canthaxantine extinction (supernatant after C16 precipitation). While in the control without C16 the total canthaxanthin remained in the supernatant, the canthaxanthin in the two batches with C16 was quantitatively bound by the C16 microbeads (Fig.

7).

In order to break down the microbeads, 3 U proteinase K (Roche) were next added to the C16 microbeads from batch (a) and incubated at 37 ° C. together with the control without protease (batch b). After the end of the incubation, centrifugation was carried out and the supernatants were measured photometrically. While in the case of the control without protease (batch b) no canthaxanthin could be measured in the supernatant, in the reaction with protease (a) canthaxanthin was quantitatively released from the C16 microbeads. set. Overall, it is clear from the experiment that canthaxanthin can be released by proteolytic degradation of the microbeads.

Example 6

Incorporation of fluorescein into Ciβ microparticles by covalent bonding

The fact that effector molecules can be covalently bound to C16 and subsequently incorporated into microbeads was demonstrated using fluorescein as an example. First, an aqueous Ci6 solution was prepared. For this purpose, lyophilized C16 was dissolved in 6 M guanidinium thiocyanate (GdmSCN) to a final concentration of 10 mg / ml. Subsequently, the GdmSCN was removed by dialysis against 5 mM potassium phosphate pH 8.0. The carboxyl groups of the C16 were activated to react with ethylenediamine upon formation of an amide (Figure 8). The following stock solutions were used for this:

- 10 mg / ml C16 5 mM potassium phosphate pH 8.0

- 250 mM 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide, hydrochloride (EDC) in water

- 250 mM / V hydroxysulfosuccinimide, sodium salt (NHS) in water

500 mM 2-morpholinoethanesulfonic acid (MES) pH 5.0

- 2 M ethylenediamine in water

The stock solutions of EDC and NHS were each used shortly before use.

For the activation of the C16-carboxyl groups, the following mixture was incubated for 15 min at room temperature:

10mM MES pH 5.0 25mM EDC 5mM NHS

The coupling of ethylenediamine to the activated C16 carboxyl groups was carried out by adding 500 mM ethylenediamine and incubating the batch for two hours. at room temperature. Subsequently, the batch was dialyzed against 5 mM potassium phosphate pH 8.0.

In a second step, fluorescein isothiocyanate was attached to the free amino group of the C16-coupled ethylene diamine (Figure 8). The following stock solutions were used for this:

- Ethylenediamine-modified C16 in 5 mM potassium phosphate pH 8.0 - 1 M sodium carbonate pH 9.0 - 10 mg / ml Fluorescein isothiocyanate (FITC) in dimethylsulfoxide (DMSO) - 1 M potassium phosphate pH 8.0 The FITC stock solution was prepared shortly before use ,

The coupling of the FITC was carried out according to the following protocol: Adding 100 mM sodium carbonate pH 9.0 and 1 mg / ml FITC to the C16 solution

Incubation for 1 h at room temperature (in the dark)

- Precipitation of the C16 with 660 mM potassium phosphate

Incubation for 1 h at room temperature (in the dark)

- Centrifugation at 10000 x g for 10 min at room temperature - 3 x washing of the pellet with 5 mM potassium phosphate pH 8.0

Dissolve the pellet in 6 M guanidinium thiocyanate (final concentration of the protein: 5 mg / ml)

- Dialysis against 5 mM potassium phosphate pH 8.0 (in the dark)

- Precipitation with 500 mM potassium phosphate pH 8.0 - 3 x washing of the pellet with water

- Resuspension in water

- freezing in liquid nitrogen

- Lyophilize (in the dark)

The precipitation of the soluble FITC-labeled C16 with potassium phosphate produces round microbeads, as in the case of untreated C16 protein, but unlike untreated C16 microbeads, they show marked fluorescence (Figure 9). The efficiency of the coupling of fluorescein to C16 was determined photometrically. To this end, a 5 mg / ml suspension of the lyophilized modified C16 protein was proteolytically digested (100 mM tris (hydroxymethyl) aminomethane (Tris) pH 8.0; 0.1% sodium dodecyl sulfate (SDS); 50 μg / ml proteinase K (Roche); Incubation for 1 h at 37 ° C). The concentration of fluorescein in the digested solution was calculated using the molar extinction coefficient ε494πm = 77000 cnτ ¹ M- ¹ . From the calculated fluorescein concentration and the known amount of protein used, the coupling efficiency could be calculated. In this way, an average coupling of 12.8 fluorescein molecules to a C16 molecule was found in the C16 microbeads. As a control, a sample was treated according to the same protocol, with the EDC and NHS being replaced by water during activation. The coupling efficiency of this sample was smaller than one fluorescein molecule per C16 molecule. It can be concluded that the binding of fluorescein to C16 follows the mechanism postulated in Figure 8 and is not due to nonspecific binding effects.

In the following, dermocosmetic preparations according to the invention are described, containing the C16 microbeads prepared according to Example 1 or Ci0 microbead canthaxanthin prepared according to Example 4.

Example 7: Use of C16 Microbead in a Day Care Emulsion - Type O / W

WS 1%:

% Ingredient (INCI)

A 1, 7 Ceteareth-6, Stearyl Alcohol

0.7 Ceteareth-25

2.0 diethylamino hydroxybenzoyl hexyl benzoate 2, 2, 00 P PEEGG - 1144 dimethicone

3.6 Cetearyl Alcohol

6.0 ethylhexyl methoxycinnamate

2.0 dibutyl adipate

B 5.0 Glycerin 0 0,, 22 D Diissodiimide EDTA

1, 0 panthenol

1, 0 C16 microbead q.s. preservative

67.8 Aqua the.

CC 44, 00 CCaapprryylliicc // CCaapprriicc TTrriiggllyycceerriiddee ,, SSooddiuminum Acrylates Copolymer

D 0.2 Sodium Ascorbyl Phosphate

1, 0 tocopheryl acetate

0.2 bisabolol

1, 0 Caprylic / Capric Triglyceride, Sodium Ascate, Tocopherol, Retinol Eq.s. Sodium hydroxides

WS 5%:

% Ingredient (INCI)

A 1, 7 Ceteareth-6, Stearyl Alcohol

0.7 Ceteareth-25

2.0 diethylamino hydroxybenzoyl hexyl benzoate

2.0 PEG-14 Dimethicone

3.6 Cetearyl Alcohol

6.0 ethylhexyl methoxycinnamate

2.0 dibutyl adipate

B 5.0 glycerin

0.2% disodium EDTA

1, 0 panthenol

5.0 C16 microbead q.s. preservative

63.8 Aqua the.

C 4.0 Caprylic / Capric Triglyceride, Sodium Acrylate Copolymer

D 0.2 Sodium Ascorbyl Phosphate

1, 0 tocopheryl acetate

0.2 bisabolol

1, 0 Caprylic / Capric Triglyceride, Sodium Ascorbate, Tocopherol, Retinol

E q.s. Sodium hydroxides

Preparation: Heat phases A and B separately from each other to about 80 ^° C. Stir phase B into phase A and homogenize. Stir phase C into combined phases A and B and homogenize again. Cool to about 40 ^° C. with stirring, add phase D, adjust the pH to about 6.5 with phase E, homogenize and cool to room temperature while stirring.

Note: The formulation is produced without inert gas. The filling must be in oxygen-impermeable packaging, e.g. Aluminum tubes take place.

Example 8: Use C16 Microbead in a Protective Day Cream - Type O / W WS 1%:

% Ingredient (INCI)

1, 7 Ceteareth-6, Stearyl Alcohol

0.7 Ceteareth-25

2.0 diethylamino hydroxybenzoyl hexyl benzoate

2.0 PEG-14 Dimethicone

3.6 Cetearyl Alcohol

6.0 ethylhexyl methoxycinnamate

2.0 dibutyl adipate B 5.0 glycerin

0.2% disodium EDTA

1, 0 panthenol

1, 0 C16 microbead q.s. preservative

68.6 Aqua the.

C 4.0 Caprylic / Capric Triglyceride, Sodium Acrylate Copolymer

D 1, 0 Sodium ascorbyl phosphates

1, 0 tocopheryl acetate

0.2 bisabolol

E q.s. Sodium hydroxides

WS 5%:

% Ingredient (INCI)

A 1, 7 Ceteareth-6, Stearyl Alcohol

0.7 Ceteareth-25

2.0 diethylamino hydroxybenzoyl hexyl benzoate

2.0 PEG-14 Dimethicone

3.6 Cetearyl Alcohol

6.0 ethylhexyl methoxycinnamate

2.0 dibutyl adipate

B 5.0 glycerin

0.2% disodium EDTA

1, 0 panthenol

5.0 C16 microbead q.s. preservative

64.6 Aqua the.

C 4.0 Caprylic / Capric Triglyceride, Sodium Acrylate Copolymer

D 1, 0 Sodium ascorbyl phosphates

1, 0 tocopheryl acetate

0.2 bisabolol

E q.s. Sodium hydroxides

Preparation: Heat phases A and B separately from each other to about 80 ^° C. Stir phase B into phase A and homogenize. Incorporate phase C into the combined phases A and B and homogenize. Cool to about 40 ^° C. while stirring. Add phase D, adjust the pH to about 6.5 with phase E and homogenize. Cool to room temperature while stirring.

Example 9: Use of C16 microbead in a facial cleansing lotion - Type O / W WS 1%:

% Ingredient (INCI)

A 10.0 Cetearyl ethylhexanoate

10.0 Caprylic / Capric Triglycerides 1, 5 Cyclopentasiloxanes, Cyclohexasilosans

2.0 PEG-40 Hydrogenated Castor OiI

B3.5 Caprylic / Capric Triglycerides, Sodium Acrylates Copolymer C 1, 0 tocopheryl acetate

0.2 bisabolol q.s. Preservatives q.s. perfume oil

D 3.0 polyquaternium-44

0.5 cocotrimonium methosulfates

0.5 ceteareth-25

2.0 Panthenol, Propylene Glycol

4.0 Propylene Glycol

0.1% disodium EDTA

1, 0 C16 microbead

60.7 Aqua.

WS! 5%:

% Ingredient (INCI)

A 10.0 Cetearyl ethylhexanoate

10.0 Caprylic / Capric Triglycerides

1, 5 cyclopentasiloxanes, cyclohexasilosans

2.0 PEG-40 Hydrogenated Castor OiI

B3.5 Caprylic / Capric Triglycerides, Sodium Acrylates Copolymer

C 1, 0 tocopheryl acetate

0.2 bisabolol q.s. Preservatives q.s. perfume oil

D 3.0 polyquaternium-44

0.5 cocotrimonium methosulfates

0.5 ceteareth-25

2.0 Panthenol, Propylene Glycol

4.0 Propylene Glycol

0.1% disodium EDTA

5.0 C16 microbead

56.7 Aqua the.

Preparation: Release phase A. Stir phase B into phase A, incorporate phase C into combined phases A and B. Dissolve phase D, stir into the combined phases A, B and C and homogenize. Stir for 15 minutes.

Example 10: Use C16 microbead canthaxanthin in a Daily Care Body Spray

WS 1%:

% Ingredient (INCI)

A 3.0 ethylhexyl methoxycinnamate

2.0 diethylamino hydroxybenzoyl hexyl benzoate

1, 0 Polyquaternium-44

3.0 Propylene Glycol

2.0 Panthenol, Propylene Glycol

1, 0 cyclopentasiloxanes, cyclohexasiloxanes

10.0 octyldodecanol

0.5 PVP

10.0 Caprylic / Capric Triglycerides

3.0 C12-15 alkyl benzoates

3.0 glycerin

1, 0 tocopheryl acetate

0.3 bisabolol

1, 0 C16 microbead canthaxanthin

59.2 Alcohol

WS 5%:

% Ingredient (INCI)

A 3.0 ethylhexyl methoxycinnamate

2.0 diethylamino hydroxybenzoyl hexyl benzoate

1, 0 Polyquaternium-44

3.0 Propylene Glycol

2.0 Panthenol, Propylene Glycol

1, 0 cyclopentasiloxanes, cyclohexasiloxanes

10.0 octyldodecanol

0.5 PVP

10.0 Caprylic / Capric Triglycerides

3.0 C 12-15 alkyl benzoates

3.0 glycerin

1, 0 tocopheryl acetate

0.3 bisabolol

5.0 C16 microbead canthaxanthin

55.2 Alcohol

Preparation: Weigh in the components of phase A and dissolve clearly.

Example 11: Use of C16 Microbead in a Skin Care Gel WS 1%:

% Ingredient (INCI)

A 3.6 PEG-40 Hydrogenated Castor OiI 15.0 Alcohol

0.1 bisabolol 0.5 tocopheryl acetate qs perfume oil

B 3.0 Panthenol

0.6 carbomer

1, 0 C16 microbead

75.4 Aqua,

C 0.8 triethanolamine

WS 5%:

% Ingredient (INCI)

A 3.6 PEG-40 Hydrogenated Castor OiI

15.0 Alcohol

0.1 bisabolol

0.5 tocopheryl acetate q.s. perfume oil

B 3.0 Panthenol

0.6 carbomer

5.0 C16 microbead

71, 4 Aqua,

C 0.8 triethanolamine

Preparation: Clear phase A clearly. Swell phase B and neutralize with phase C.

Stir phase A into the homogenized phase B and homogenize.

Example 12: Use of C16 microbead canthaxanthin in an aftershave lotion

WS 1%:

% Ingredient (INCI)

A 10.0 Cetearyl ethylhexanoate

5.0 tocopheryl acetate 1, 0 bisabolol

0.1 perfume oil

0.3 Acrylates / C 10-30 Alkyl Acrylate Crosspolymer

B 15.0 Alcohol

1, 0 Panthenol 3.0 Glycerin

1, 0 C16 microbead canthaxanthin

0.1 triethanolamine

63.5 Aqua the.

WS 5%:

% Ingredient (INCI)

A 10.0 Cetearyl ethylhexanoate

5.0 tocopheryl acetates

1, 0 bisabolol 0.1 perfume oil

0.3 Acrylates / C 10-30 Alkyl Acrylate Crosspolymer

B 15.0 Alcohol 1, 0 panthenol

3.0 glycerin

5.0 C16 microbead canthaxanthin

0.1 triethanolamine

59.5 Aqua the.

Preparation: Mix the components of phase A. Dissolve phase B, work in phase A and homogenize.

Example 13: Use C16 Microbead in an After Sun Lotion WS 1%:

% Ingredient (INCI)

0.4 Acrylates / C 10-30 Alkyl Acrylate Crosspolymer

15.0 Cetearyl ethylhexanoates

0.2 bisabolol

1, 0 tocopheryl acetate q.s. perfume oil

B 1, 0 panthenol

15.0 Alcohol

3.0 glycerin

1, 0 C16 microbead

63.2 Aqua,

0.2 triethanolamine

WS 5%

% Ingredient (INCI)

0.4 Acrylates / C 10-30 Alkyl Acrylate Crosspolymer

15.0 Cetearyl ethylhexanoates

0.2 bisabolol

1, 0 tocopheryl acetate q.s. perfume oil

B 1, 0 panthenol

15.0 Alcohol

3.0 glycerin

5.0 C16 microbead

59.2 Aqua,

0.2 triethanolamine

Preparation: Mix the components of phase A. Stir phase B into phase A while homogenizing. Neutralize with Phase C and homogenize again.

Example 14: Use of C16 microbead canthaxanthin in a sunscreen lotion WS 1%:

% Ingredient (INCI) A 4,5 Ethylhexyl Methoxycinnamate

2.0 Diethylamino Hydroxybenzoyl Hexyl Benzoate 3.0 Octocrylene 2.5 di-C12-13 alkyl malates

0.5 tocopheryl acetate

4.0 polyglyceryl-3 methyl glucose distearate

B 3,5 Cetearyl isononanoate

1, 0 VP / eicosene copolymer

5.0 isohexadecane

2.5 di-C12-13 alkyl malates

3.0 Titanium dioxides, trimethoxycaprylylsilanes

C 5.0 Glycerin 1 1 ,, 00 Sodium Cetearyl Sulfate

0.5 xanthan gum

1, 0 C16 microbead canthaxanthin

59.7 Aqua the.

D 1, 0 phenoxyethanol, methylparaben, ethylparaben, butylparaben, propylparaben, isobutylparaben

0.3 bisabolol

WS 5%:

% Ingredient (INCI)

A 4,5 ethylhexyl methoxycinnamate

2.0 diethylamino hydroxybenzoyl hexyl benzoate

3.0 octocrylene

2.5 di-C12-13 alkyl malates

0.5 tocopheryl acetate

4.0 polyglyceryl-3 methyl glucose distearate

B 3,5 Cetearyl isononanoate

1, 0 VP / eicosene copolymer

5.0 isohexadecane

2.5 di-C12-13 alkyl malates

3.0 Titanium dioxides, trimethoxycaprylylsilanes

C 5.0 glycerin

1, 0 Sodium Cetearyl Sulfate

0.5 xanthan gum

5.0 C16 microbead canthaxanthin

55.7 Aqua.

0.3 bisabolol

Preparation: Heat the components of phases A and B separately to about 80 ^° C. Stir phase B into phase A and homogenize. Heat phase C to about 80 ^° C. and stir into the combined phases A and B while homogenizing. Cool with stirring to about 40 ⁰ C, add phase D and homogenize again.

Example 15: Use of C16 Microbead in a Sunscreen Lotion - Type O / W WS 1%: % Ingredient (INCI)

A 2.0 Ceteareth-6, Stearyl Alcohol

2.0 Ceteareth-25

3.0 tribehenin

2.0 Cetearyl Alcohol

2.0 cetearyl ethylhexanoate

5.0 ethylhexyl methoxycinnamate

1, 0 ethylhexyl triazone

1, 0 VP / eicosene copolymer

7.0 isopropyl myristate

B 5.0 Zinc oxides, triethoxycaprylylsilanes

C 0.2 xanthan gum

0.5 hydroxyethyl acrylate / sodium acryloyl dimethyl taurate copolymer,

Squalane, polysorbate 60

0.2% disodium EDTA

5.0 Propylene Glycol

0.5 panthenol

1, 0 C16 microbead

60,9 Aqua the.

D 0.5 phenoxyethanol, methylparaben, butylparaben, ethylparaben, propylparaben, isopropylparaben

1, 0 tocopheryl acetate

0.2 bisabolol

WS! 5%:

% Ingredient (INCI)

A 2.0 Ceteareth-6, Stearyl Alcohol

2.0 Ceteareth-25

3.0 tribehenin

2.0 Cetearyl Alcohol

2.0 cetearyl ethylhexanoate

5.0 ethylhexyl methoxycinnamate

1, 0 ethylhexyl triazone

1, 0 VP / eicosene copolymer

7.0 isopropyl myristate

B 5.0 Zinc oxides, triethoxycaprylylsilanes

C 0.2 xanthan gum

0.5 hydroxyethyl acrylate / sodium acryloyl dimethyl taurate copolymer,

Squalane, polysorbate 60

0.2% disodium EDTA

5.0 Propylene Glycol

0.5 panthenol

5.0 C16 microbead

56.9 Aqua the.

D 0.5 phenoxyethanol, methylparaben, butylparaben, ethylparaben, propylparaben, isopropylparaben 1, 0 tocopheryl acetate 0.2 bisabolol

Preparation: Heat phase A to approx. 80 ^° C., stir in phase B and homogenize for 3 minutes. Also heat phase C to 80 ^° C. and stir into the combined phases A and B while homogenizing. Cool to about 40 ° C, stir in phase D and homogenize again.

Example 16: Use of C16 Microbead in a Sunscreen Lotion - Type O / W

WS 1%:

% Ingredient (INCI)

A 3,5 Ceteareth-6, Stearyl Alcohol

1, 5 Ceteareth-25

7.5 ethylhexyl methoxycinnamate

2.0 diethylamino hydroxybenzoyl hexyl benzoate

2.0 cyclopentasiloxanes, cyclohexasiloxanes

0.5 Bees Wax

3.0 Cetearyl Alcohol

10.0 Caprylic / Capric Triglycerides

B 5.0 Titanium Dioxide, Silica, Methicone, Alumina

C 3.0 glycerin

0.2% disodium EDTA

0.3 xanthan gum

1, 0 decyl glucosides

2.0 Panthenol, Propylene Glycol

1, 0 C16 microbead

56.3 Aqua the.

D 1, 0 tocopheryl acetate

0.2 bisabolol q.s. Perfume oil q.s. preservative

WS 5%

% Ingredient (INCI)

A 3,5 Ceteareth-6, Stearyl Alcohol

1, 5 Ceteareth-25

7.5 ethylhexyl methoxycinnamate

2.0 diethylamino hydroxybenzoyl hexyl benzoate

2.0 cyclopentasiloxanes, cyclohexasiloxanes

0.5 Bees Wax

3.0 Cetearyl Alcohol

10.0 Caprylic / Capric Triglycerides

B 5.0 Titanium Dioxide, Silica, Methicone, Alumina

C 3.0 glycerin

0.2% disodium EDTA

0.3 xanthan gum 1, 0 decyl glucosides

2.0 Panthenol, Propylene Glycol

5.0 C16 microbead

52.3 Aqua the.

D 1, 0 tocopheryl acetate

0.2 bisabolol q.s. Perfume oil q.s. preservative

Preparation: Heat phase A to approx. 80 ^° C., stir in phase B and homogenize for 3 minutes.

Also heat phase C to 80 ^° C. and stir into the combined phases A and B while homogenizing. Cool to about 40 ° C, stir in phase D and homogenize again.

Example 17: Use of C16 microbead canthaxanthin in a foot balm

WS 1%:

% Ingredient (INCI)

A 2.0 Ceteareth-6, Stearyl Alcohol

2.0 Ceteareth-25

5.0 Cetearyl ethylhexanoate

4.0 Cetyl Alcohol

4.0 glyceryl stearate

5.0 mineral oil

0.2 menthol

0.5 camphor

B 69.3 Aqua the.

1, 0 C16 microbead canthaxanthin q.s. preservative

C 1, 0 bisabolol

1, 0 tocopheryl acetate

D 5.0 Witch Hazel Extract

WS 5%

% Ingredient (INCI)

A 2.0 Ceteareth-6, Stearyl Alcohol

2.0 Ceteareth-25

5.0 Cetearyl ethylhexanoate

4.0 Cetyl Alcohol

4.0 glyceryl stearate

5.0 mineral oil

0.2 menthol

0.5 camphor

B 65,3 Aqua the.

5.0 C16 microbead canthaxanthin q.s. preservative

C 1.0 bisabolol 1, 0 Tocopheryl Acetate D 5.0 Witch Hazel Extract

Preparation: The components of the phases A and B separately to approx men 80 ⁰ C heat up. Stir phase B into phase A while homogenizing. Cool with stirring to approx.

40 ⁰ C, add the phases C and D and posthumogenise shortly. Cool to room temperature while stirring.

Example 18: Use of C16 microbead canthaxanthin in a W / O emulsion with bisabolol

WS 1%:

% Ingredient (INCI)

A 6.0 PEG-7 Hydrogenated Castor OiI

8.0 Cetearyl ethylhexanoates

5.0 isopropyl myristate

15.0 mineral oil

0.3 mg stearate

0.3 Aluminum Stearate

2.0 PEG-45 / dodecyl glycol copolymer

B 5.0 glycerin

0.7 magnesium sulphates

1, 0 C16 microbead canthaxanthin

55.6 Aqua the.

C 0.5 tocopheryl acetate

0.6 bisabolol

WS 5%:

% Ingredient (INCI)

A 6.0 PEG-7 Hydrogenated Castor OiI

8.0 Cetearyl ethylhexanoates

5.0 isopropyl myristate

15.0 mineral oil

0.3 mg stearate

0.3 Aluminum Stearate

2.0 PEG-45 / dodecyl glycol copolymer

B 5.0 glycerin

0.7 magnesium sulphates

51, 6 Aqua the.

5.0 C16 microbead canthaxanthin

C 0.5 tocopheryl acetate

Preparation: Heat phases A and B separately from each other to approx. 85 ° C. Stir phase B into phase A and homogenize. Cool with stirring to about 40 ⁰ C, add phase C and briefly homogenize again. Cool to room temperature while stirring.

Example 19: Foam Conditioner with Fixer WS 1%

% Ingredient (INCI)

A 10.0 PVP / VA copolymer

0.2 hydroxyethyl cetyldimonium phosphates

0.2 Ceteareth-25

0.5 Dimethicone Copolyol q.s. perfume oil

10.0 Alcohol

1, 0 C16 microbead canthaxanthin

68.1 Aqua.

10.0 propane / butane

WS 5%

% Ingredient (INCI)

A 10.0 PVP / VA copolymer

0.2 hydroxyethyl cetyldimonium phosphates

0.2 Ceteareth-25

0.5 Dimethicone Copolyol q.s. perfume oil

10.0 Alcohol

5.0 C16 microbead canthaxanthin

64.1 Aqua.

10.0 propane / butane

Preparation: Weigh the components of phase A together, stir until everything is dissolved and bottled.

Example 20: Foam conditioner

WS 1%

% Ingredient (INCI)

A 1, 0 Polyquaternium-4

0.5 hydroxyethyl cetyldimonium phosphates

1, 0 C16 microbead q.s. Perfume oil q.s. preservative

91, 5 Aqua the.

6.0 propanes / butanes

WS 5%% Ingredient (INCI) A 1, 0 Polyquaternium-4

0.5 hydroxyethyl cetyldimonium phosphates

5.0 C16 microbead canthaxanthin q.s. Perfume oil q.s. preservative

87.5 Aqua the.

6.0 propanes / butanes

Production: Weigh the components of phase A together, stir until everything is clearly dissolved and bottled.

Example 21: Foam conditioner

WS 1%% ingredient (INCI)

A 1, 0 Polyquaternium-11

0.5 hydroxyethyl cetyldimonium phosphates

1, 0 C16 microbead q.s. Perfume oil q.s. preservative

91, 5 Aqua the.

6.0 propanes / butanes

WS 5%

% Ingredient (INCI)

A 1, 0 Polyquaternium-11

0.5 Hydroxyethyl Cetyldimonium Phosphate 5.0 C16 Microbead q.s. Perfume oil q.s. Preservative 87.5 Aqua dem.

6.0 propanes / butanes

Example 22: Styling foam

WS 1%

% Ingredient (INCI)

A 0.5 Laureth-4 qs perfume oil B 77.3 Aqua the.

10.0 polyquaternium-28

1, 0 C16 microbead

0.5 dimethicone copolyol

0.2 Ceteareth-25

0.2 panthenol

0.1 PEG-25 PABA

0.2 hydoxyethylene I cel I loose

10.0 HFC 152A

WS 5%

% Ingredient (INCI)

A 0.5 Laureth-4 q.s. perfume oil

B 73,3 Aqua the.

10.0 polyquaternium-28

5.0 C16 microbead

0.5 dimethicone copolyol

0.2 Ceteareth-25

0.2 panthenol

0.1 PEG-25 PABA

0.2 hydoxyethylene I cel I loose

C 10.0 HFC 152 A

Preparation: Mix the components of phase A. Add the components of phase B one by one and dissolve. Fill with phase C.

Example 23: Styling foam

WS 1%

% Ingredient (INCI)

A 2, 0 cocotrimonium methosulfate q- S. perfume oil

B 78, 5 Aqua the.

6, 7 acrylates copolymer

0, 6 AMP

1, 0 C16 microbead canthaxanthin

0, 5 dimethicone copolyol

0, 2 Ceteareth-25

0, 2 panthenol

0 .1 PEG-25 PABA 0.2 hydroxyethylcellulose

C 10.0 HFC 152 A

WS 5%

% Ingredient (INCI)

2.0 cocotrimony methosulfate q.s. perfume oil

B 74.5 Aqua the.

6,7 acrylates copolymer

0.6 AMP

5.0 Ciδ microbead canthaxanthin

0.5 dimethicone copolyol

0.2 Ceteareth-25

0.2 panthenol

0.1 PEG-25 PABA

0.2 hydoxyethylene I cel I loose

10.0 HFC 152 A

Example 24: Styling foam

WS 1%

% Ingredient (INCI)

A 2.0 cocotrimony methosulfate q.s. perfume oil

B 7.70 Polyquaternium 44 1, 0 C16 microbead canthaxanthin q.s. Preservative 79.3 Aqua dem.

C 10.0 propane / butane

WS 5%

% Ingredient (INCI)

A 2,0 cocotrimonium methosulfate qs perfume oil B 7.70 Polyquaternium-44

5.0 C16 microbead canthaxanthin q.s. preservative

75.3 Aqua the.

C 10.0 propane / butane

Preparation: Mix the components of phase A. Clear the components of phase B, then stir phase B into phase A. Adjust the pH to 6-7, fill with phase C.

Example 25: Styling foam

WS 1%

% Ingredient (INCI)

A 2.00 cocotrimonium methosulfate q.s. perfume oil

B 72,32 Aqua the. 2.00 VP / Acrylates / Lauryl Methacrylate Copolymer

0.53 AMP

1.00 C16 microbead canthaxanthin

0.20 Ceteareth-25

0.50 panthenol 0.05 benzophenone-4

0.20 Amodimethicone, Cetrimonium Chloride, Trideceth-12

15.00 Alcohol

C 0.20 hydroxyethylcellulose

D 6,00 Propane / Butane

WS 5%

% Ingredient (INCI)

A 2.00 cocotrimonium methosulfate q.s. perfume oil

B 68,32 Aqua the. 2.00 VP / Acrylates / Lauryl Methacrylate Copolymer

0.53 AMP

5.00 C16 microbead canthaxanthin

0.20 Ceteareth-25

0.50 panthenol 0.05 benzophenone-4

0.20 Amodimethicone, Cetrimonium Chloride, Trideceth-12 15.00 Alcohol

C 0.20 hydroxyethylcellulose

D 6,00 Propane / Butane

Preparation: Mix the components of phase A. Add the components of phase B one by one and dissolve. Dissolve phase C in the mixture of A and B, then adjust the pH to 6-7. Fill with phase D.

Example 26: Styling foam

WS 1%

% Ingredient (INCI)

A 2.00 Cetrimonium Chloride q.s. perfume oil

B 67,85 Aqua the.

7.00 Polyquaternium-46

1, 00 C16 microbead

0.20 Ceteareth-25

0.50 panthenol

0.05 benzophenone-4

0.20 Amodimethicone, Cetrimonium Chloride, Trideceth-12

15.00 Alcohol

C 0.20 hydroxyethylcellulose

D 6,00 Propane / Butane

WS 5% o%, Ingredient (INCI)

A 2.00 Cetrimonium Chloride q.s. perfume oil

B 63,85 Aqua the.

7.00 Polyquaternium-46 5.00 C16 microbead

0.20 Ceteareth-25

0.50 panthenol

0.05 benzophenone-4

0.20 Amodimethicone, Cetrimonium Chloride, Trideceth-12 15.00 Alcohol C 0.20 hydroxyethylcellulose

D 6,00 Propane / Butane

Example 27: Styling Foam

WS 1%

% Ingredient (INCI)

A q.s. PEG-40 Hydrogenated Castor q.s. perfume oil

85.5 Aqua dem.

B 7.0 Sodium Polystyrene Sulfonate

1, 0 C16 microbead canthaxanthin

0.5 Cetrimonium Bromide q.s. preservative

C 6.0 propane / butane

Styling foam

WS 5% o%. Ingredient (INCI)

A q.s. PEG-40 Hydrogenated Castor OiI q.s. Perfume oil 81, 5 Aqua dem.

B 7.0 Sodium Polystyrene Sulfonate 5.0 C16 microbead canthaxanthin

0.5 Cetrimonium Bromide q.s. preservative

C 6.0 propane / butane

Preparation: Solubilize phase A. Weigh phase B into phase A and solve it clearly. Adjust the pH to 6-7, fill with phase C. Example 28: Styling foam

WS 1%

% Ingredient (INCI) A qs PEG-40 Hydrogenated Castor OiI qs perfume oil

92.0 Aqua the.

B 0.5 polyquaternium-10

1, 0 C16 microbead

0.5 Cetrimonium Bromide q.s. preservative

C 6.0 propane / butane

WS 5% o%. Ingredient (INCI)

A q.s. PEG-40 Hydrogenated Castor OiI q.s. perfume oil

88.0 Aqua the.

B 0.5 Polyquaternium-10 5.0 C16 microbead

0.5 Cetrimonium Bromide q.s. preservative

C 6.0 propane / butane

Preparation: Solubilize phase A. Weigh phase B into phase A and solve it clearly. Adjust the pH to 6-7, fill with phase C.

Example 29: Styling foam

WS 1%

% Ingredient (INCI)

A q.s. PEG-40 Hydrogenated Castor OiI q.s. perfume oil

82.5 Aqua the.

B 10.0 Polyquaternium-16

1, 0 C16 microbead canthaxanthin 0.5 hydroxyethyl cetyldimonium phosphates q.s. preservative

C 6.0 propane / butane WS 5%

% Ingredient (INCI)

A q.s. PEG-40 Hydrogenated Castor OiI q.s. perfume oil

78.5 Aqua the.

B 10.0 Polyquaternium-16

5.0 Ciδ microbead canthaxanthin 0.5 hydroxyethyl cetyldimonium phosphates q.s. preservative

C 6.0 propane / butane

Example 30: Styling foam

WS 1% o%. Ingredient (INCI)

A 2.0 cocotrimony methosulfate q.s. perfume oil

B 84.0 Aqua dem.

2.0 Chitosan

1, 0 C16 microbead

0.5 dimethicone copolyol 0.2 ceteareth-25

0.2 panthenol

0.1 PEG-25 PABA

C 10.0 HFC 152 A

WS 5%

% Ingredient (INCI)

A 2.0 cocotrimony methosulfate q.s. perfume oil

B 80.0 Aqua dem. 2.0 Chitosan

5.0 C16 microbead

0.5 dimethicone copolyol

0.2 Ceteareth-25

0.2 panthenol

0.1 PEG-25 PABA

C 10.0 HFC 152 A

Example 31: care shampoo

WS 1% o%. Ingredient (INCI)

30, 0 Sodium Laureth Sulfate

6, 0 Sodium cocoamphoacetate

6, 0 cocamidopropyl betaines

3, 0 Sodium Laureth Sulfate, Glycol Distearate, Cocamide MEA, Laureth-10

1, 0 C16 microbead

7, 7 Polyquaternium-44

2, 0 Amodimethicone q- S. Perfume oil q- S. Preservative

1, 0 Sodium Chloride

43, 3 Aqua the.

B α. S. Citric Acid

WS 5% o%, Ingredient (INCI)

A 30.0 Sodium Laureth Sulfate

6.0 Sodium Cocoamphoacetate

6.0 Cocamidopropyl Betaine

3.0 Sodium Laureth Sulfate, Glycol Distearate, Cocamide MEA, Laureth-10

5.0 C16 microbead 7.7 polyquaternium-44

2.0 Amodimethicone q.s. Perfume oil q.s. preservative

1, 0 Sodium Chloride 39.3 Aqua dem. B qs Citric Acid

Preparation: Mix and dissolve the components of phase A. Adjust the pH to 6-7 with citric acid.

Example 32: shower gel

WS 1%

% Ingredient (INCI)

A 40.0 Sodium Laureth Sulfate

5.0 decyl glucosides

5.0 Cocamidopropyl betaines

1, 0 C16 microbead canthaxanthin 1, 0 panthenol q.s. Perfume oil q.s. preservative

2.0 Sodium Chloride

46.0 Aqua the.

B q.s. Citric Acid

WS 5%

% Ingredient (INCI)

A 40.0 Sodium Laureth Sulfate

5.0 decyl glucosides

5.0 Cocamidopropyl betaines

5.0 C16 microbead canthaxanthin

1, 0 panthenol q.s. Perfume oil q.s. preservative

2.0 Sodium Chloride

42.0 Aqua the.

B q.s. Citric Acid

Example 33: Shampoo

WS 1%

% Ingredient (INCI)

A 40.0 Sodium Laureth Sulfate

5.0 Sodium C12-15 Pareth-15 Sulfonates 5.0 Decyl Glucoside qs perfume oil

0.1 phytantriol

44.6 Aqua the.

1, 0 C16 microbead

0.3 polyquaternium-10

1, 0 panthenol q.s. preservative

1, 0 Laureth-3

2.0 Sodium Chloride

WS 5%

% Ingredient (INCI)

A 40.0 Sodium Laureth Sulfate

5.0 Sodium C12-15 Pareth-15 Sulfonates

5.0 Decyl Glucosides q.s. perfume oil

0.1 phytantriol

40.6 Aqua the.

5.0 C16 microbead

0.3 polyquaternium-10

1, 0 panthenol q.s. preservative

1, 0 Laureth-3

2.0 Sodium Chloride

Example 34: Shampoo

WS 1%

% Ingredient (INCI)

A 15.00 cocamidopropyl betaines

10.00 Disodium Cocoamphodiacetate

5.00 Polysorbate 20

5.00 decyl glucosides q.s. Perfume oil q.s. preservative

1, 00 C16 microbead

0.15 guar hydroxypropyltrimonium chlorides

2.00 laureth-3

58.00 Aqua the. qs Citric Acid B 3.00 PEG-150 distearate

WS 5%

% Ingredient (INCI)

15.00 cocamidopropyl betaines

10.00 Disodium Cocoamphodiacetate

5.00 Polysorbate 20

5.00 decyl glucosides q.s. Perfume oil q.s. preservative

5.00 C16 microbead

0.15 guar hydroxypropyltrimonium chlorides

2.00 laureth-3

54.00 Aqua the. q.s. Citric Acid

B 3.00 PEG-150 distearate

Production: Weigh in the components of phase A and dissolve. Adjust the pH to 6-7. Add phase B and heat to approx. 50 ^° C. Cool to room temperature while stirring.

Example 35: Moisturizing Body Care Cream

WS 1%

% Ingredient (INCI)

2.0 Ceteareth-25

2.0 Ceteareth-6, Stearyl Alcohol

3.0 Cetearyl ethylhexanoate

1, 0 dimethicone

4.0 Cetearyl Alcohol

3.0 Glyceryl Stearate SE

5.0 mineral oil

4.0 Simmondsia Chinensis (Jojoba) Seed OiI

3.0 Mineral OiI, Lanolin Alcohol

B 5.0 Propylene Glycol

1, 0 C16 microbead

1, 0 panthenol

0.5 Mg Aluminum Silicate Q.s Preservative

65.5 Aqua the.

α.s. perfume oil D qs Citric Acid

WS 5%

% Ingredient (INCI)

A 2.0 Ceteareth-25

2.0 Ceteareth-6, Stearyl Alcohol

3.0 Cetearyl ethylhexanoate

1, 0 dimethicone

4.0 Cetearyl Alcohol

3.0 Glyceryl Stearate SE

5.0 mineral oil

4.0 Simmondsia Chinensis (Jojoba) Seed OiI

3.0 Mineral OiI, Lanolin Alcohol

B 5.0 Propylene Glycol

5.0 C16 microbead

1, 0 panthenol

0.5 Mg Aluminum Silicate Q.s Preservative

61, 5 Aqua the.

C q.s. perfume oil

D q.s. Citric Acid

Preparation: Heat phases A and B separately to about 80 ^° C. Stir phase B prehomogenising briefly, then phase B into phase A and re-approve homogenisieren.Abkühlen to about 40 ⁰ C, phase C and homogenize thoroughly again. Adjust the pH to 6-7 with citric acid.

Example 36: Moisturizing Body Care Cream

WS 1%

% Ingredient (INCI)

A 6.0 PEG-7 Hydrogenated Castor OiI

10.0 Cetearyl ethylhexanoates

5.0 isopropyl myristate

7.0 Mineral OiI

0.5 Shea Butter (Butyrospermum Parkii)

0.5 Aluminum Stearate

0.5 mg stearate

0.2 bisabolol

0.7 Quaternium-18 hectorites B 5.0 Dipropylene glycol

0.7 magnesium sulphates

1, 0 C16 microbead q.s. preservative

62.9 Aqua.

C q.s. perfume oil

WS 5%

% Ingredient (INCI)

A 6.0 PEG-7 Hydrogenated Castor OiI

10.0 Cetearyl ethylhexanoates

5.0 isopropyl myristate

7.0 Mineral OiI

0.5 Shea Butter (Butyrospermum Parkii)

0.5 Aluminum Stearate

0.5 mg stearate

0.2 bisabolol

0.7 Quaternium-18 hectorites

B 5.0 Dipropylene glycol

0.7 magnesium sulphates

5.0 C16 microbead q.s. preservative

58.9 Aqua.

C q.s. perfume oil

Preparation: Heat phases A and B separately to about 80 ^° C. Bring phase B into phase A and homogenize. Cool with stirring to about 40 ⁰ C, add phase C and homogenize again. Allow to cool to room temperature while stirring.

Example 37: Liquid Make-up - Type O / W

WS 1%

% Ingredient (INCI)

A 2, 0 ceteareth-6, stearyl alcohol

2, 0 Ceteareth-25

6, 0 glyceryl stearate

1, 0 Cetyl Alcohol

8, 0 Mineral OiI

7, 0 cetearyl ethylhexanoate

0 .2 Dimethicone B 3.0 Propylene glycol

1, 0 panthenol q.s. preservative

1, 0 C16 microbead canthaxanthin

61, 9 Aqua the.

C 0.1 bisabolol q.s. perfume oil

D 5.7 C.I. 77 891, Titanium Dioxide

1, 1 Iron Oxides

WS 5%

% Ingredient (INCI)

A 2.0 Ceteareth-6, Stearyl Alcohol

2.0 Ceteareth-25

6.0 glyceryl stearates

1, 0 Cetyl Alcohol

8.0 mineral OiI

7.0 cetearyl ethylhexanoate

0.2 dimethicone

B 3.0 Propylene glycol

1, 0 panthenol

5.0 C16 microbead canthaxanthin q.s. preservative

57.9 Aqua the.

C 0.1 bisabolol q.s. perfume oil

D 5.7 C.I. 77 891, Titanium Dioxide

1.1 Iron oxides

Preparation: Heat phases A and B separately to about 80 ^° C. Stir phase B into phase A and homogenize. Cool with stirring to about 40 ⁰ C, add phases C and D and thoroughly homogenize again. Allow to cool to room temperature while stirring.

Example 38

In the following, dermocosmetic preparations according to the invention are described, comprising the C16 microbead prepared according to Examples 1 or C16 microbead canthaxanthin prepared according to Example 4. The following are parts by weight of an aqueous solution. Clear shampoo

Clear conditioner shampoo

Foam O / W emulsions

Conditioner Shampoo with pearlescent

Adjust pH to 6.0

Clear conditioner shampoo

Adjust pH to 6.0

Clear conditioner shampoo with volume effect

Adjust pH to 6.0

Gel Cream

OW Sunscreen formulation

Sticks

PIT emulsion

Gel Cream

OW Formulations Homebrewers

Hydrodispersion self-tanner

WO-emulsion

Solid stabilized emulsion (Pickering emulsions)

Sticks

oil gel

Example 39:

The following formulations describe cosmetic sunscreen preparations comprising a combination of at least one inorganic pigment, preferably zinc oxide and / or titanium dioxide, and organic UV-A and UV-B filters.

The following formulations are prepared in a customary manner known to the person skilled in the art.

The content of C16 microbead prepared according to Example 1 or C16 microbead canthaxanthin prepared according to Example 4 refers to 100% active ingredient. The active compounds according to the invention can be used both in pure form and as an aqueous solution. In the case of the aqueous solution, the content of water must be the. be adapted in the respective formulation.

0.10 allantoin allantoin

66.70 water to the. Aqua the.

D 2.00 simulgel NS hydroxyethyl acrylate / sodium acryloyl dimethyl taurate copolymer, squalane, polysorbate 60 q.s. preservative

A 5.00 Uvinul N 539 T Octocrylene

2.00 Uvinul A PIus Diethylamino Hydroxybenzoyl Hexyl Benzoate

0.80 RyIo PG 11 polyglyceryl dimer soyate

1, 00 Span 60 Sorbitan Stearate

0.50 vitamin E acetate tocopheryl acetate

3.00 Dracorin 100 SE Glyceryl Stearate, PEG-100 Stearate

1, 00 Cremophor CO 410 PEG-40 Hydrogenated Castor OiI

B 3.00 Z-COTE MAX Zinc Oxide (and) Diphenyl Capryl Methicone

1, 00 Cetiol SB 45 Butyrospermum Parkii (Shea Butter)

6.50 Finsolv TN C12-15 alkyl benzoates

C 5.00 Butylene Glycol Butylene Glycol

0.30 Keltrol Xanthan gum

0.10 Edeta BD Disodium EDTA

0.10 allantoin allantoin

1% C16 microbead canthaxanthin

2.0 Mexoryl SX Terephthalidene Dicamphor Sulfonic Acid

66.20 water to the. Aqua the.

, 70 Candelilla Wax LT 281 LJ Candelilla (Euphorbia Cerifera) Wax, 80 Beeswax 3050 PH Bees Wax, 20 TeCero Wax 30445 Microcrystalline Wax, 20 TeCero Wax 1030 K Microcrystalline Wax, 34 Cutina CP Cetyl Palmitate, 40 Vaseline Petrolatum, 30 Softisan 100 Hydrogenated Coco-Glycerides, 00 Luvitol EHO Cetearyl Ethylhexanoate, 17 Bisabolol Nat. Bisabolol, 84 Vitamin E Acetate Tocopheryl Acetate, 42 D, L-Alpha Tocopherol Tocopherol

1% C16 microbead canthaxanthin, 38 castor oil Castor (Ricinus communis) OiI

Benzoate

2.00 Uvinul N 539 T Octocrylene

B 5.00 T-Lite SF-S Titanium Dioxide, Silica Hydrate, Alumina Hydrate, Methicone / Dimethicone Copolymer

C 3.00 1, 2-propylene glycol Care Propylene Glycol

0.30 Abiol Imidazolidinyl urea

1, 00 magnesium sulfate 7-hydrate magnesium sulfates

0.5% C16 microbead

Ad 100 water to the. Aqua the. q.s. preservative

Claims

claims

1. Use of protein microbeads in cosmetics.

2. Use according to claim 1, characterized in that it is

Silk protein microbeads.

3. Use according to claim 1, characterized in that they are microbeads which have been prepared from an intrinsically unfolded protein.

4. Use according to claim 1, characterized in that the protein microbeads are couplings of a protein (i) and an effector molecule (ii).

5. Use according to claim 3, characterized in that the protein (i) is a C16 spider silk protein.

6. Use according to claim 1, characterized in that the effector molecule (II) is a UV absorber.

7. Use according to claim 1, characterized in that the protein microbead can be produced by a process comprising the following steps: (i) dissolving a protein in a first solvent, (ii) inducing a phase separation in the solvent phase and protein-rich phase emulsified therein by an additive, (iii) curing of the protein-rich phase, optionally by adding a cross-linker, (iv) isolation and, if appropriate, purification of the protein microbeads produced in step (iii).

8. Use according to claim 1, characterized in that the protein

Microbead is used in skin cosmetics.

9. Cosmetic compositions containing at least one protein

Microbead and at least one active ingredient from the group of UV absorbers.