AU5163199A - Cosmetic formulation containing ectoine derivatives, enzymes, vitamins and/or vitamin derivatives - Google Patents
Cosmetic formulation containing ectoine derivatives, enzymes, vitamins and/or vitamin derivatives Download PDFInfo
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- AU5163199A AU5163199A AU51631/99A AU5163199A AU5163199A AU 5163199 A AU5163199 A AU 5163199A AU 51631/99 A AU51631/99 A AU 51631/99A AU 5163199 A AU5163199 A AU 5163199A AU 5163199 A AU5163199 A AU 5163199A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
- A61K8/66—Enzymes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/67—Vitamins
- A61K8/676—Ascorbic acid, i.e. vitamin C
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/52—Stabilizers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q1/00—Make-up preparations; Body powders; Preparations for removing make-up
- A61Q1/02—Preparations containing skin colorants, e.g. pigments
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q1/00—Make-up preparations; Body powders; Preparations for removing make-up
- A61Q1/02—Preparations containing skin colorants, e.g. pigments
- A61Q1/04—Preparations containing skin colorants, e.g. pigments for lips
- A61Q1/06—Lipsticks
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q1/00—Make-up preparations; Body powders; Preparations for removing make-up
- A61Q1/02—Preparations containing skin colorants, e.g. pigments
- A61Q1/08—Preparations containing skin colorants, e.g. pigments for cheeks, e.g. rouge
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q1/00—Make-up preparations; Body powders; Preparations for removing make-up
- A61Q1/02—Preparations containing skin colorants, e.g. pigments
- A61Q1/10—Preparations containing skin colorants, e.g. pigments for eyes, e.g. eyeliner, mascara
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
- A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/004—Aftersun preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/10—Washing or bathing preparations
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- Veterinary Medicine (AREA)
- Birds (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Cosmetics (AREA)
Description
WO 00/07559 PCT/EP99/05238 - 1 COSMETIC FORMULATION COMPRISING ECTOIN DERIVATIVES, ENZYMES, VITAMINS AND/OR VITAMIN DERIVATIVES The invention relates to cosmetic formulations 5 comprising a) one or more compounds chosen from compounds of the formulae Ia and Ib
R
3 R 1 4 N-(C-R)n la R N R"!l H R 3 14b HN-(C-R )~ 10R N R2 b, the physiologically compatible salts of the compounds of the formulae Ia and Ib, and the stereoisomeric forms of the compounds of the 15 formulae Ia and Ib, where Ri is H or alkyl, R 2 is H, COOH, COO-alkyl or CO-NH-Rs, 20
R
3 and R 4 are in each case independently of one another H or OH, n is 1, 2 or 3, 25 alkyl is an alkyl radical having 1 to 4 carbon atoms, and WO 00/07559 PCT/EP99/05238 -2 R 5 is H, alkyl, an amino acid radical, dipeptide radical or tripeptide radical 5 and b) one or more substances chosen from enzymes, vitamins and vitamin derivatives. 10 Enzymes, vitamins and vitamin derivatives frequently have low stability and are exposed in vitro to a number of denaturing or destabilizing conditions. For example, such substances are sensitive to changes in the medium which surrounds them and to temperature fluctuations. 15 While vitamins and vitamin derivatives are usually stable as powders, this is not always the case for aqueous formulations. The storage of enzymes, vitamins and vitamin derivatives over an extended period therefore leads to a decrease in their activity. The 20 use of such substances in cosmetics is particularly difficult since these topically applied products are subject to considerable temperature and moisture variations on the skin and, following uniform distribution on the skin, usually dry out rapidly. This 25 can lead to denaturation or destabilization of the enzymes, vitamins and vitamin derivatives before they pass from the depot on the surface of the skin to their site of action in deeper layers of the epidermis. 30 If enzymes, vitamins and vitamin derivatives are nevertheless to be used as constituents of cosmetics, they have to be used in high concentrations and be transported as quickly as possible to the site of action by suitable transportation or carrier systems. 35 The problem of the decrease in activity of enzymes, vitamins and vitamin derivatives occurs in particular in formulations in which the substances have to have WO 00/07559 PCT/EP99/05238 -3 the highest possible activity over an extended period. This is the case, for example, for formulations with a uniform release of the enzymes, vitamins and vitamin derivatives over an extended period, which is also 5 referred to as the "depot effect". For the above reasons, it is necessary to stabilize enzymes, vitamins and vitamin derivatives in cosmetic formulations and to protect them from denaturation. 10 The object was therefore to provide cosmetic formulations comprising substances chosen from enzymes, vitamins and vitamin derivatives which are notable for the fact that such substances present in the 15 formulation have high activity which lasts as long as possible and, moreover, the cosmetic formulations are suitable in an advantageous manner for the care and prophylaxis of dry and/or flaky skin. 20 Surprisingly, we have now found that this object is achieved by the provision of cosmetic formulations comprising a) one or more compounds chosen from compounds of the 25 formulae Ia and Ib R 3 1 4 N-(C-R), la R N R2 H R 3 HN-(C-R), lb, R N/< R 2 30 WO 00/07559 PCT/EP99/05238 -4 the physiologically compatible salts of the compounds of the formulae Ia and Ib, and the stereoisomeric forms of the compounds of the formulae Ia and Ib, where 5 Ri is H or alkyl, R 2 is H, COOH, COO-alkyl or CO-NH-R , 10 R3 and R4 are in each case independently of one another H or OH, n is 1, 2 or 3, 15 alkyl is an alkyl radical having 1 to 4 carbon atoms, and RE 5is H, alkyl, an amino acid radical, dipeptide radical or tripeptide radical 20 and b) one or more substances chosen from enzymes, vitamins and vitamin derivatives. 25 Within the scope of the present invention, all compounds above and below chosen from the compounds of the formulae Ia and Ib, the physiologically compatible salts of the compounds of formulae Ia and Ib, and the 30 stereoisomeric forms of the compounds of the formulae Ia and Ib are referred to as "ectoin or ectoin derivatives". The invention further relates to 35 - the use of one or more substances chosen from enzymes, vitamins and vitamin derivatives and one or more compounds chosen from the compounds of the WO 00/07559 PCT/EP99/05238 -5 formulae Ia and Ib, the physiologically compatible salts of the compounds of the formulae Ia and Ib, and the stereoisomeric forms of the compounds of the formulae Ia and Ib for the preparation of a 5 cosmetic formulation, - a method of preparing a cosmetic formulation, characterized in that one or more compounds chosen from the compounds of the formulae Ia and Ib, the 10 physiologically compatible salts of the compounds of the formulae Ia and Ib, and the stereoisomeric forms of the compounds of the formulae Ia and Ib and one or more substances chosen from enzymes, vitamins and vitamin derivatives, optionally with 15 auxiliaries and/or carriers are converted to a suitable formulation form, and - the use of one or more compounds chosen from the compounds of the formulae Ia and Ib, the 20 physiologically compatible salts of compounds of the formulae Ia and Ib and the stereoisomeric forms of the compounds of the formulae Ia and Ib for the protection and/or stabilization of one or more substances present in a cosmetic formulation, 25 chosen from enzymes, vitamins and vitamin derivatives. The ectoins or ectoin derivatives present in the cosmetic formulations according to the invention 30 protect the substances chosen from enzymes, vitamins and vitamin derivatives in the formulation from stress factors, such as variations in the water content and the temperature following topical application to the skin. In addition, ectoin or its derivatives protect 35 said substances against high salt or ion concentrations in the cosmetic formulation according to the invention. As a result of the stabilizing effect of the ectoin or the ectoin derivatives, the substances present in the WO 00/07559 PCT/EP99/05238 -6 cosmetic formulation, chosen from enzymes, vitamins and vitamin derivatives, are more slowly destabilized or denatured following application to the surface of the skin, meaning that a depot effect with high activity of 5 the substances chosen from enzymes, vitamins and vitamin derivatives is possible. The substances chosen from enzymes, vitamins and vitamin derivatives are, however, also protected by ectoin or its derivatives in the formulation prior to topical application. This is 10 evident in an advantageous manner from an increase in the storage stability of a formulation which comprises substances of this type. The protection of the substances chosen from enzymes, 15 vitamins and vitamin derivatives in the cosmetic formulation by ectoin or its derivatives is advantageously effective in various ways on the human skin. For example, the antioxidative effects, the effects directed against the aging of skin ("anti-aging 20 effects"), the effects directed against the formation of wrinkles, the skin-smoothing effects and the keratolytic effects of these substances on the human skin are aided or protected as a result, i.e. the premature loss or the premature reduction of these 25 effects as a result of the loss or the decrease in activity of the substances chosen from enzymes, vitamins and vitamin derivatives is counteracted. The invention further relates to the use of 30 a) one or more compounds chosen from compounds of the formulae Ia and Ib Lit! WO 00/07559 PCT/EP99/05238 -7 R 3 N-(C-R') RA N lj" la I H R 3
HN--(C-R
4 ) Rn N12b , the physiologically compatible salts of the compounds of the formulae Ia and Ib, and the 5 stereoisomeric forms of the compounds of the formulae Ia and Ib, where R 1 is H or alkyl, 10 R2 is H, COOH, COO-alkyl or CO-NH-R ,
R
3 and R 4 are in each case independently of one another H or OH, 15 n is 1, 2 or 3, alkyl is an alkyl radical having 1 to 4 carbon atoms, and 20 R is H, alkyl, an amino acid radical, dipeptide radical or tripeptide radical and 25 b) one or more substances chosen from enzymes, vitamins and vitamin derivatives WO 00/07559 PCT/EP99/05238 -8 for the preparation of a cosmetic formulation - for the care and/or prophylaxis of dry and/or flaky skin or scalp, in particular for increasing 5 and/or stabilizing the moisture content of the skin, - for protecting human skin from stress factors, in particular from dryness as a result of high 10 temperatures or very low temperatures with low atmospheric humidity and/or from high salt concentration on the skin, - for protecting cells, proteins and/or biomembranes 15 of human skin, - for protecting the microflora of human skin and/or - for stabilizing the skin barrier. 20 Healthy human skin is colonized on its surface, the Stratum corneum, by a large number of microorganisms which live commensally. From the great diversity of these microorganisms, only a few live continually on 25 the skin and thus form the resident skin flora. The main representatives of the resident flora on the human skin are Staphylococci, Micrococci, coryneform bacteria and Pityrospora. These live in small colonies on the surface of the Stratum corneum and in the outer 30 epidermis. A second group of microorganisms, which settles temporarily from the outside, in particular on exposed areas of skin, is referred to as transient flora and cannot settle permanently on healthy skin whose microenvironment is heavily determined by the 35 resident microflora. In various regions of the body, the composition of the skin flora varies depending on the microenvironment of the skin. The density of the microorganisms adapts to the respective skin -1' WO 00/07559 PCT/EP99/05238 -9 environment so that the ecology of these regions of the body is not unbalanced by excessive settlement by microorganisms. Compared with the normal state of the skin, the number of microorganisms decreases in the 5 case of dry skin, while the number of microorganisms increases in the case of moist skin, e.g. as a result of inflammatory changes in the case of eczema, by up to 1000-fold. 10 Being the barrier layer and surface of the human body, the skin is exposed to a large number of external stress factors. The human skin is an organ which, having diverse specialized cell types - keratinocytes, melanocytes, Langerhans cells, Merkel cells and 15 intercalated sensory cells - protects the body against external influences. A differentiation should be made here between external physical, chemical, and biological influences on the human skin. External physical influences include thermal and mechanical 20 influences, and the effect of radiation. External chemical influences are, in particular, the effect of toxins and allergens. External biological influences include the effect of foreign organisms and the metabolic products thereof. 25 The surface of the human skin is covered by a fatty film which, depending on the given ratios, is to be considered as an oil-in-water or a water-in-oil emulsion and contains numerous active ingredients, such 30 as e.g. enzymes and vitamins. This fatty film, which has been formed from the lipids released from the sebaceous glands and keratinocytes, preserves the moisture of the skin and protects the body as a skin barrier against unfavorable environmental factors. This 35 sensitive equilibrium of the skin barrier is disturbed by external or internal factors.
WO 00/07559 PCT/EP99/05238 - 10 The microorganisms of human skin are subjected to various stress factors. For example, they can be damaged by drying out or by high salt concentrations on the surface of the skin, e.g. after perspiring, which 5 can lead to damage of the skin barrier. However, some of these microorganisms - Staphylococci, Micrococci, Corynebacteria and Brevibacteria - usually have the ability to form compatible solutes in order to protect against drying out or high salt concentration and thus 10 contribute to the formation of an intact skin barrier. The compatible solutes, which are also referred to as stress protection substances, are low molecular weights of substances in cytoplasm. 15 Hitherto, it has mainly been attempted to effect retention of the skin moisture by hydrophilic substances which themselves bind water (E.A. Galinski, Experientia 49 (1993) 487-496). However, these hydrophilic substances bind water molecules of the 20 water of hydration as well as free water molecules. Although this leads to a binding of water molecules, it does not lead to a protection of the hydration sheaths of cells, proteins and cell membranes. 25 Ectoin-containing cosmetic formulations protect cells, protein, enzymes, vitamins, DNA, cell membranes and biomembranes of the skin against damage as a result of drying out and the withdrawal of water. The hydration effect of ectoin stabilizes the water equilibrium of 30 the Stratum corneum and the skin barrier. Ectoin prevents dry and flaky skin. In addition, ectoin-containing cosmetic formulations protect the microflora of the skin, which is important 35 for an intact skin barrier, against stress as a result of drying out and high ion concentration after perspiring. The stabilization of the resident skin flora by ectoin or its derivatives is an important WO 00/07559 PCT/EP99/05238 - 11 prerequisite for the equilibrium of the microenvironment of the skin and the formation of an intact skin barrier. 5 Ectoin and the ectoin derivatives are low molecular weight cyclic amino acid derivatives which can be obtained from various halophilic microorganisms. Both ectoin and hydroxyectoin have the advantage that they do not react with the cell metabolism. 10 DE 43 42 560 describes the use of ectoin and ectoin derivatives as moisture-donors in cosmetic products. The compounds chosen from the compounds of the formulae 15 Ia and Ib, the physiologically compatible salts of the compounds of the formulae Ia and Ib and the stereoisomeric forms of the compounds of the formulae Ia and Ib can be present in the cosmetic preparations as optical isomers, diastereomers, racemates, 20 zwitterions, cations or as a mixture of these. Of the compounds chosen from the compounds of the formulae Ia and Ib, the physiological compatible salts of the compounds of the formulae Ia and Ib and the stereoisomeric forms of the compounds of the formulae 25 Ia and Ib, preference is given to those in which R 1 is H or CH 3 , R2 is H or COOH, R3 and R 4 in each case independently of one another are H or OH and n is 2. Of the compounds chosen from the compounds of the formulae Ia and Ib, the physiologically compatible salts of the 30 compounds of the formulae Ia and Ib and the stereoisomeric forms of the compounds of the formulae Ia and Ib, particular preference is given to the compounds (S)-1,4,5, 6-tetrahydro-2-methyl-4 pyrimidecarboxylic acid (ectoin) and (S,S)-1,4,5,6 35 tetrahydro-5-hydroxy-2-methyl-4-pyrimidinecarboxylic acid (hydroxyectoin).
WO 00/07559 PCT/EP99/05238 - 12 The term "amino acid" means the stereoisomeric forms, e.g. D and L forms, the following compounds: alanine, p-alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, 5 isoleucine, leucine, lysine, methionine, phenylalanine, serine, threonine, tryptophan, tyrosine, valine, y-aminobutyrate, Ns-acetyllysine, NS-acetylornithine, Ny-acetyldiaminobutyrate and Nc-acetyldiaminobutyrate. L-amino acids are preferred. 10 Amino acid radicals are derived from the corresponding amino acids. The radicals of the following amino acids are 15 preferred: alanine, @-alanine, asparagine, aspartic acid, glutamine, glutamic acid, glycine, serine, threonine, valine, y-aminobutyrate, Ns-acetyllysine, N6-acetylornithine, Ny-acetyldiaminobutyrate and Na-acetyldiaminobutyrate. 20 The di- and tripeptide radicals are acid amides according to their chemical nature and decompose upon hydrolysis into 2 or 3 amino acids. The amino acids in the di- and tripeptide radicals are bonded together by 25 amide bonds. Preferred di- and tripeptide radicals are built up from the preferred amino acids. The alkyl groups include the methyl group CH 3 , the ethyl group C 2
H
5 , the propyl groups CH 2
CH
2
CH
3 and 30 CH (CH 3 )2 and the butyl groups CH 2
CH
2
CH
2
CH
3 , H 3
CCHCH
2
CH
3 ,
CH
2
CH(CH
3
)
2 and C(CH 3
)
3 . The preferred alkyl group is the methyl group. Preferred physiologically compatible salts of the 35 compounds of the formulae Ia and Ib are, for example, alkali metal, alkaline earth metal or ammonium salts, such as Na, K, Mg or Ca salts, and salts derived from the organic bases triethylamine or tris (2- WO 00/07559 PCT/EP99/05238 - 13 hydroxyethyl)amine. Further preferred physiologically compatible salts of the compounds of the formulae Ia and Ib arise by reaction with inorganic acids, such as hydrochloric acid, sulfuric acid and phosphoric acid, 5 or with organic carboxylic or sulfonic acids, such as acetic acid, citric acid, benzoic acid, maleic acid, fumaric acid, tartaric acid and p-toluenesulfonic acid. Compounds of the formulae Ia and Ib in which basic and 10 acidic groups such as carboxyl or amino groups are present in equal number form internal salts. The preparation of the compounds of the formula [sic] Ia and Ib is described in the literature 15 (DE 43 42 560). (S)-1,4,5,6-tetrahydro-2-methyl-4 pyrimidinecarboxylic acid or (S,S)-1,4,5,6-tetrahydro 5-hydroxy-2-methyl-4-pyrimidinecarboxylic acid can also be obtained microbiologically (Severin et al., J. Gen. Microb. 138 (1992) 1629-1638). 20 Enzymes chosen from superoxide dismutase, protease, lipase, pepsin, trypsin, chymotrypsin, elastase, diastase, catalase, dehydrogenase, urease, lysozyme, neuraminidase, peroxidase, glutathione peroxidase, 25 phosphatase, dismutase, papain, bromelain, alcalase, aminopeptidase K, aminopeptidase M, carboxypeptidase A, carboxypeptidase B, carboxypeptidase Y, clostripain, collagenase, ficin, leucine amidopeptidase, lytic enzyme, pronase E and proteinase K are preferably 30 present in the cosmetic formulations according to the invention, particularly preferably superoxide dismutase, protease, lipase and dismutase. Vitamins and vitamin derivatives chosen from vitamin A, 35 vitamin A propionate, vitamin A palmitate, vitamin A acetate, retinol, vitamin B, thiamine chloride hydrochloride (vitamin Bi) , riboflavin (vitamin B 2 ), nicotinamide, vitamin C (ascorbic acid), vitamin D, WO 00/07559 PCT/EP99/05238 - 14 ergocalciferol (vitamin D 2 ), vitamin E, DL-a tocopherol, tocopherol E acetate, tocopherol hydrogensuccinate, vitamin K 1 , esculin (vitamin P active ingredient), thiamine (vitamin Bi), nicotinic 5 acid (niacin), pyridoxine, pyridoxal, pyridoxamine, (vitamin B 6 ), panthothenic acid, biotin, folic acid and cobalamin (vitamin B 12 ) are preferably present in the cosmetic formulations according to the invention, particularly preferably vitamin A palmitate, vitamin C, 10 DL-a-tocopherol, tocopherol E acetate, nicotinic acid, pantothenic acid and biotin. All of the enzymes, vitamins and vitamin derivatives present in the formulations according to the invention 15 can be synthesized by known methods or can be obtained commercially. The cosmetic formulation is prepared by converting one or more compounds chosen from the compounds of the 20 formulae Ia and Ib, the physiologically compatible salts of the compounds of the formulae Ia and Ib and the stereoisomeric forms of the compounds of the formulae Ia and Ib and one or more substances chosen from enzymes, vitamins and vitamin derivatives 25 optionally with auxiliaries and/or carriers into a suitable formulation form. The auxiliaries and carriers originate from the group of carriers, preservatives and other customary auxiliaries. 30 The cosmetic formulations based on one or more compounds chosen from the compounds of the formulae Ia and Ib, the physiologically compatible salts of the compounds of the formulae Ia and Ib and the stereoisomeric forms of the compounds of the formulae 35 Ia and Ib and one or more substances chosen from enzymes, vitamins and vitamin derivatives are applied externally.
WO 00/07559 PCT/EP99/05238 - 15 Examples of application forms which may be mentioned are: solutions, suspensions, emulsions, pastes, ointments, gels, creams, lotions, powders, soaps, surfactant-containing cleansing preparations, oils and 5 sprays. In addition to one or more compounds chosen from the compounds of the formulae Ia and Ib, the physiologically compatible salts of the compounds of the formulae Ia and Ib and the stereoisomeric forms of the compounds of the formulae Ia and Ib and one or more 10 substances chosen from enzymes, vitamins and vitamin derivatives, any customary carriers, auxiliaries and optionally further active ingredients are added to the formulation. 15 Preferred auxiliaries originate from the group of preservatives, antioxidants, stabilizers, solubility promoters, vitamins, colorants, odor improvers. In addition to one or more compounds chosen from the 20 compounds of the formulae Ia and Ib, the physiologically compatible salts of the compounds of the formulae Ia and Ib and the stereoisomeric forms of the compounds of the formulae Ia and Ib and one or more substances chosen from enzymes, vitamins and vitamin 25 derivatives, ointments, pastes, creams and gels can comprise the customary carriers, e.g. animal and vegetable fats, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silica, talc and zinc oxide or mixtures of 30 these substances. In addition to one or more compounds chosen from the compounds of the formulae Ia and Ib, the physiologically compatible salts of the compounds of 35 the formulae Ia and Ib and the stereoisomeric forms of the compounds of the formulae Ia and Ib and one or more substances chosen from enzymes, vitamins and vitamin derivatives, powders and sprays can comprise the WO 00/07559 PCT/EP99/05238 - 16 customary carriers, e.g. lactose, talc, silica, aluminum hydroxide, calcium silicate and polyamide powder or mixtures of these substances. Sprays can additionally comprise the customary propellants, e.g. 5 chlorofluorocarbons, propane/butane or dimethyl ether. In addition to one or more compounds chosen from the compounds of the formulae Ia and Ib, the physiologically compatible salts of the compounds of 10 the formulae Ia and Ib and the stereoisomeric forms of the compounds of the formulae Ia and Ib and one or more substances chosen from enzymes, vitamins and vitamin derivatives, solutions and emulsions can comprise the customary carriers, such as solvents, solubility 15 promoters and emulsifiers, e.g. water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3 diethylene glycol butyl ether, oils, in particular cottonseed oil, groundnut oil, wheatgerm oil, olive 20 oil, castor oil and sesame oil, glycerol fatty acid esters, polyethylene glycols and fatty acid esters of sorbitan or mixtures of these substances. In addition to one or more compounds chosen from the 25 compounds of the formulae Ia and Ib, the physiologically compatible salts of the compounds of the formulae Ia and Ib and the stereoisomeric forms of the compounds of the formulae Ia and Ib and one or more substances chosen from enzymes, vitamins and vitamin 30 derivatives, suspensions can comprise the customary carriers, such as liquid diluents, e.g. water, ethanol or propylene glycol, suspending agents, e.g. ethoxylated isostearyl alcohols, polyoxyethylene sorbitol esters and polyoxyethylene sorbitan esters, 35 microcrystaline cellulose, aluminum metahydroxide, bentonite, agar agar and tragacanth or mixtures of these substances.
WO 00/07559 PCT/EP99/05238 - 17 In addition to one or more compounds chosen from the compounds of the formulae Ia and Ib, the physiologically compatible salts of the compounds of the formulae Ia and Ib and the stereoisomeric forms of 5 the compounds of the formulae Ia and Ib and one or more substances chosen from enzymes, vitamins and vitamin derivatives, soaps can comprise the customary carriers, such as alkali metal salts of fatty acids, salts of fatty acid half-esters, fatty acid protein 10 hydrolyzates, isothionates [sic], lanolin, fatty alcohol, vegetable oils, plant extracts, glycerol, sugars or mixtures of these substances. In addition to one or more compounds chosen from the 15 compounds of the formulae Ia and Ib, the physiologically compatible salts of the compounds of the formulae Ia and Ib and the stereoisomeric forms of the compounds of the formulae Ia and Ib and one or more substances chosen from enzymes, vitamins and vitamin 20 derivatives, surfactant-containing cleaning products can comprise the customary carrier substances, such as salts of fatty alcohol sulfates, fatty alcohol ether sulfates, sulfosuccinic half-esters, fatty acid protein hydrolyzates, isothionates [sic], imidazolinium 25 derivatives, methyltaurates, sarcosinates, fatty acid amide ether sulfates, alkylamidobetaines, fatty alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable and synthetic oils, lanolin derivatives, ethoxylated glycerol fatty acid esters or 30 mixtures of these substances. In addition to one or more compounds chosen from the compounds of the formulae Ia and Ib, the physiologically compatible salts of the compounds of 35 the formulae Ia and Ib and the stereoisomeric forms of the compounds of the formulae Ia and Ib and one or more substances chosen from enzymes, vitamins and vitamin derivatives, face and body oils can comprise the WO 00/07559 PCT/EP99/05238 - 18 customary carrier substances such as synthetic oils, such as fatty acid esters, fatty alcohols, silicone oils, natural oils, such as plant oils and oily plant extracts, paraffin oils, lanolin oils or mixtures of 5 these substances. Further typically cosmetic application forms are also lipstick, lipcare sticks, mascara, eyeliner, eyeshadows, blusher, powder, emulsion and wax 10 foundation, and sunscreen, presun and aftersun preparations. The proportion of the compounds chosen from the compounds of the formulae Ia and Ib, the 15 physiologically compatible salts of the compounds of the formulae Ia and Ib and the stereoisomeric forms of the compounds of the formulae Ia and Ib in the cosmetic formulation according to the invention is preferably from 0.0001 to 50% by weight, particularly preferably 20 from 0.001 to 10% by weight, based on the total cosmetic formulation. The proportion of enzymes in the cosmetic formulation according to the invention is preferably from 0.0001 to 25 10% by weight, particularly preferably from 0.001 to 5% by weight, based on the total cosmetic formulation. The proportion of vitamins and/or vitamin derivatives in the cosmetic formulation according to the invention 30 is preferably from 0.0001 to 50% by weight, particularly preferably from 0.001 to 20% by weight, based on the total cosmetic formulation. The proportion of compounds chosen from the compounds 35 of the formulae Ia and Ib, the physiologically compatible salts of the compounds of the formulae Ia and Ib and the stereoisomeric forms of the compounds of e formulae Ia and Ib together with the substances WO 00/07559 PCT/EP99/05238 - 19 chosen from enzymes, vitamins and vitamin derivatives in the cosmetic formulation according to the invention is preferably from 0.0001 to 50% by weight, particularly preferably from 0.001 to 20% by weight, 5 based on the total cosmetic formulation. The weight ratio of the compounds chosen from the compounds of the formulae Ia and Ib, the physiologically compatible salts of the compounds of 10 the formulae Ia and Ib and the stereoisomeric forms of the compounds of the formulae Ia and Ib to the enzymes in the cosmetic formulation according to the invention is preferably from 1 : 1 to 1000 1, particularly preferably from 1 : 1 to 100 : 1. 15 The weight ratio of the compounds chosen from the compounds of the formulae Ia and Ib, the physiologically compatible salts of the compounds of the formulae Ia and Ib and the stereoisomeric forms of 20 the compounds of the formulae Ia and Ib to the vitamins and/or vitamin derivatives of the cosmetic formulation according to the invention is preferably from 1 : 100 to 1000 : 1, particularly preferably from 1 : 10 to 100 : 1. 25 The enzyme activity can be determined both in vivo and in vitro by known methods. In vitro determinations of the enzyme activity can be carried out, for example, following the action of stress factors such as e.g. 30 heat or dryness, using validated enzyme tests which are commercially available for many enzymes, such as e.g. the "elastase kit". In vivo determinations of the activity of skin enzymes, such as e.g. protease or dismutase, are carried out, for example, by firstly 35 pretreating a certain area of skin with ectoin and then exposing it to a drying stress. Following removal of the enzymes on the skin, e.g. by tape-stripping, enzyme determination is carried out by known methods.
WO 00/07559 PCT/EP99/05238 - 20 Following removal of the skin cells in layers, the enzyme activity of the individual cell layers can be determined. 5 Within the scope of the present invention, it was investigated whether the enzymes important for cell protection, catalase, glutathione peroxidase, superoxide dismutase and elastase, can be protected against thermal stress by treatment with ectoin. 10 In aerobic metabolic processes, the action of oxidases in the peroxisomes (cell organells) produces hydrogen peroxide, which is immediately decomposed by the catalase which is also present. Following proteolytic 15 activation by trypsin, elastase hydrolytically cleaves the peptide chains of fibrin, hemoglobin, albumin, casein and other proteins, but in particular elastin. Elastase is also found, for example, in certain leucocytes, where it is involved in phagocytosis and 20 microorganism defense. In order to prevent disruption of connective tissue in the body by the elastase, its activity has to be carefully controlled, which occurs in the blood stream via inhibitors al-antritrypsin and others, e.g. a2-macroglobin. 25 It has been found that catalase, glutathione peroxidase, superoxide dismutase and elastase are more stable toward thermal stress if they are treated with ectoin. The stabilization of these enzymes treated with 30 ectoin is shown in Fig. 1 to Fig. 4, in particular Fig. 1 shows the stabilization of catalase, Fig. 2 the stabilization of glutathione peroxidase, Fig. 3 the stabilization of superoxide dismutase and Fig. 4 the stabilization of elastase. In each of the figures, the 35 difference in the enzyme activity of the enzyme treated with ectoin is compared with the corresponding enzyme not treated with ectoin, the activity of the untreated enzyme being equated with 100%. For example, following ii, WO 00/07559 PCT/EP99/05238 - 21 incubation at a temperature of 400C, the activity of catalase treated with ectoin is approximately 25% higher than catalase not treated with ectoin (see Fig. 1). By contrast, following incubation at a 5 temperature of 500C, the activity of catalase treated with ectoin is around almost 120% higher than catalase not treated with ectoin, i.e. catalase treated with ectoin is more than twice as active following incubation at this temperature as catalase not treated 10 with ectoin (see Fig. 1). Broadly speaking, the stabilizing effect of ectoin on the enzyme activity is considerably more marked for all enzymes investigated for higher incubation temperatures. The greatest effects were found in each case for incubation 15 temperatures of 400C and especially of 50*C, particularly for the enzyme catalase and glutathione peroxidase. To establish the stabilizing effect of ectoin or its 20 derivatives on vitamins and vitamin derivatives, their chemical and physical stability can be proven by standard tests. All compounds or components which can be used in 25 cosmetic formulations are either known and available commercially or can be synthesized by known methods. The examples below serve to illustrate the invention and are in no way to be regarded as a limitation. All 30 percentages are percentages by weight.
WO 00/07559 PCT/EP99/05238 - 22 Example 1 The following components were used to prepare a skincare gel (0/W) according to the invention comprising ectoin and vitamin C: 5 % by wt. A Almond oil (2) 8.0 Eutanol G (3) 2.0 Luvitol EHO (4) 6.0 Oxynex K liquid (Art. No. 108324) (1) 0.05 B Vitamin C (Art. No. 500074) (1) 0.5 Carion F liquid (Art. No. 102993) (1) 4.0 Preservative q.s. Water, ad 100 demineralized C Sepigel 305 (5) 3.0 D Ectoin (1) 1.0 Preservatives which may be used are 0.05% of propyl 4-hydroxybenzoate (Art. No. 107427)or 0.15% of methyl 4-hydroxybenzoate (Art. No. 106757) 10 Preparation: The combined phase B is introduced slowly into phase C with stirring. The predissolved phase A is then added. The mixture is stirred until the phases are mixed 15 homogeneously. Phase D is then added and stirred until homogeneous. Sources of supply: (1) Merck KGaA, Darmstadt 20 (2) Gustav Heess, Stuttgart (3) Henkel KGaA, Disseldorf (4) BASF AG, Ludwigshafen (5) Seppic, France C I WO 00/07559 PCT/EP99/05238 - 23 Example 2 The following components were used to prepare a skincare gel (0/W) according to the invention 5 comprising ectoin and protease: % by wt. A Almond oil (2) 8.0 Eutanol G (3) 2.0 Luvitol EHO (4) 6.0 Oxynex K liquid (Art. No. 108324) (1) 0.05 B Protease (pepsin) (Art. No. 107185) (1) 0.01 Carion F liquid (Art. No. 102993) (1) 4.0 Preservative q.s. Water, ad 100 demineralized C Sepigel 305 (5) 3.0 D Ectoin (1) 1.0 Preservatives which may be used are 0.05% of propyl 4-hydroxybenzoate (Art. No. 107427)or 10 0.15% of methyl 4-hydroxybenzoate (Art. No. 106757) Preparation: The combined phase B is introduced slowly into phase C with stirring. The predissolved phase A is then added. 15 The mixture is stirred until the phases are mixed homogeneously. Phase D is then added and stirred until homogeneous. Sources of supply: 20 (1) Merck KGaA, Darmstadt (2) Gustav Heess, Stuttgart (3) Henkel KGaA, Ddsseldorf (4) BASF AG, Ludwigshafen WO 00/07559 PCT/EP99/05238 - 24 (5) Seppic, France Example 3 The enzyme-stabilizing action of ectoin against thermal 5 stress is investigated in vitro. For this, the enzymes catalase, glutathione peroxidase, superoxide dismutase and elastase are incubated with ectoin - and for the control without ectoin - for 30 minutes in a water bath at various temperatures, and then their activity is 10 measured. The base medium for the incubation is 0.25 molar tris-HCl buffer solution with a pH of 6.8. The enzyme concentration is 0.05 mg/ml and the concentration of ectoin is 1 mol/l. 15 The enzyme activity is determined - for catalase according to the method by A. Claiborne [A. Claiborne 'Catalase Activity' in: R.A. Greenwald (Ed.), Handbook of Methods for 20 Oxygen Radical Research, CRC Press, Boca Raton, FL. (1986) 283-284], - for glutathione peroxidase according to the method by L. Floh and W.A. Giinzler [L. Flohe et al., 25 Methods Enzymol., 105 (1989) 114-121], - for superoxide dismutase according to the method by H.P. Nissen and H.W. Kreysel [H.W. Kreysel et al., 'Superoxide Dismutase in Human Semen', Klin. 30 Wochenschr. 61 (1983) 63-65] and - for elastase according to the method by L. Hornebeck and W. Hornebeck [W. Hornebeck et al., 'Characterisation of Human Skin Fibroblasts 35 Elastase Activity', J. Invest. Dermatol. 91 (5) (1998) 472-477].
WO 00/07559 PCT/EP99/05238 - 25 The results for catalase are given in Fig. 1, for glutathione peroxidase in Fig. 2, for superoxide dismutase in Fig. 3 and for elastase in Fig. 4. In each of the figures, the difference in the enzyme activity 5 of the enzyme treated with ectoin is compared with the corresponding enzyme not treated with ectoin as "activity [%]" for the various incubation temperatures, the activity of the untreated enzyme being equated as 100%. For an incubation temperature of 500C, the 10 activity of catalase treated with ectoin is, accordingly, almost 120% higher than that of catalase not treated with ectoin, i.e. for this incubation temperature, the activity of catalase treated with ectoin is approximately 2.2 times as high as the 15 activity of catalase not treated with ectoin (see Fig. 1). The values for Fig. 1 to 4 are listed in Tab. 1 to 4. 20 Tab. 1 Investigation of the catalase activity. Temperature [0C] 20 30 140 150 Activity [%] 2.5 10.4 26.1 117.9 Tab. 2 Investigation of the glutathione peroxidase activity. 25 Temperature [*C] 20 30 140 150 Activity [%] 3.5 1.4 20.8 39.6 Tab. 3 Investigation of the superoxide dismutase activity Temperature [SC] 20 40 50 V':Activity [%] 4.9 14.4 17.4 WO 00/07559 PCT/EP99/05238 - 26 Tab. 4 Investigation of the elastase activity Temperature
[
0 C] 30 40 150 Activity [%] 4.0 15.0 25.7 5 It has been found that catalase, glutathione peroxidase, superoxide dismutase and elastase are more stable toward thermal stress if they are treated with ectoin. Generally speaking, the stabilizing action of ectoin on the enzyme activity is more marked for all 10 enzymes investigated for higher incubation temperatures. The greatest effects were found in each case for incubation temperatures of 40*C and 50 0 C, in particular for the enzymes catalase and glutathione peroxidase.
Claims (20)
1. Cosmetic formulation comprising 5 a) one or more compounds chosen from compounds of the formulae Ia and Ib N Ra II H R3 HN-(C-R 4 ) R N R b 10 the physiologically compatible salts of the compounds of the formulae Ia and Ib, and the stereoisomeric forms of the compounds of the formulae Ia and Ib, where 15 R is H or alkyl, R is H, COOH, COO-alkyl or CO-NH-R, R3 and R4 are in each case independently of one 20 another H or OH, n is 1, 2 or 3, alkyl is an alkyl radical having 1 to 4 carbon 25 atoms, and WO 00/07559 PCT/EP99/05238 - 28 R5 is H, alkyl, an amino acid radical, dipeptide radical or tripeptide radical and 5 b) one or more substances chosen from enzymes, vitamins and vitamin derivatives.
2. Cosmetic formulation according to claim 1, 10 characterized in that the compounds of the formulae Ia and Ib are chosen from the compounds (S)-1,4,5, 6 -tetrahydro-2-methyl-4-pyrimidine carboxylic acid and (S,S)-1,4,5,6-tetrahydro-5 hydroxy-2-methyl-4-pyrimidine carboxylic acid. 15
3. Cosmetic formulation according to one of claims 1 or 2, characterized in that the enzymes are chosen from superoxide dismutase, protease, lipase, pepsin, trypsin, chymotrypsin, elastase, diastase, 20 catalase, dehydrogenase, urease, lysozyme, neuraminidase, peroxidase, glutathionee peroxidase, phosphatase, dismutase, papain, bromelain, alcalase, aminopeptidase K, aminopeptidase M, carboxypeptidase A, 25 carboxypeptidase B, carboxypeptidase Y, clostripain, collagenase, ficine, leucine amidepeptidase, lytic enzyme, pronase E and proteinase K. 30
4. Cosmetic formulation according to one of claims 1 to 3, characterized in that the vitamins and/or vitamin derivatives are chosen from vitamin A, vitamin A propionate, vitamin A palmitate, vitamin A acetate, retinol, vitamin B, thiamine chloride 35 hydrochloride, riboflavin, nicotinamide, vitamin C, vitamin D, ergocalciferol, vitamin E, DL-a tocopherol, tocopherol E acetate, tocopherol hydrogensuccinate, vitamin K 1 , esculin, thiamine, WO 00/07559 PCT/EP99/05238 - 29 nicotinic acid, pyridoxine, pyridoxal, pyridoxamine, panthothenic acid, biotin, folic acid and cobalamin.
5 5. Cosmetic formulation according to one of claims 1 to 4, characterized in that the proportion of the compounds chosen from the compounds of the formulae Ia and Ib, the physiologically compatible salts of the compounds of the formulae Ia and Ib, 10 and the stereoisomeric forms of the compounds of the formulae Ia and Ib is from 0.0001 to 50% by weight, based on the total cosmetic formulation, and the proportion of the enzymes is from 0.0001 to 10% by weight, based on the total cosmetic 15 formulation.
6. Cosmetic formulation according to one of claims 1 to 5, characterized in that the proportion of the compounds chosen from the compounds of the 20 formulae Ia and Ib, the physiologically compatible salts of the compounds of the formulae Ia and Ib, and the stereoisomeric forms of the compounds of the formulae Ia and Ib is from 0.0001 to 50% by weight, based on the total cosmetic formulation, 25 and the proportion of the vitamins and/or vitamin derivatives is from 0.001 to 20% by weight, based on the total cosmetic formulation.
7. Cosmetic formulation according to one of claims 1 30 to 6, characterized in that it is in the form of a solution, a suspension, an emulsion, a paste, an ointment, a gel, a cream, a lotion, a powder, a soap, a surfactant-containing cleansing preparation, an oil, a lipstick, a lipcare stick, 35 a mascara, an eyeliner, eyeshadows, blusher, a powder, emulsion or wax foundation, a sunscreen, presun and aftersun preparation or a spray. WO 00/07559 PCT/EP99/05238 - 30
8. Use of a) one or more compounds chosen from compounds of the formulae Ia and Ib 5 R3 N ~R2 la H R3 HN-(C-R ) R N R lb, the physiologically compatible salts of the compounds of the formulae Ia and Ib, and the 10 stereoisomeric forms of the compounds of the formulae Ia and Ib, where R I is H or alkyl, 15 R 2 is H, COOH, COO-alkyl or CO-NH-R, R3 and R4 are in each case independently of one another H or OH, 20 n is 1, 2 or 3, alkyl is an alkyl radical having 1 to 4 carbon atoms, and 25 R is H, alkyl, an amino acid radical, dipeptide radical or tripeptide radical WO 00/07559 PCT/EP99/05238 - 31 for the protection and/or stabilization of one or more substances present in a cosmetic formulation, chosen from enzymes, vitamins and vitamin derivatives. 5
9. Use of a) one or more compounds chosen from compounds of the formulae Ia and Ib 10 R 3 N-(C-R 4)L R AN R 2 H HN--(C-Rb) R 1 N R 2 the physiologically compatible salts of the compounds of the formulae Ia and Ib, and the 15 stereoisomeric forms of the compounds of the formulae Ia and Ib, where R 1 is H or alkyl, 20 R is H, COOH, COO-alkyl or CO-NH-R 5 R 3 and R 4 are in each case independently of one another H or OH, 25 n is 1, 2 or 3, WO 00/07559 PCT/EP99/05238 - 32 alkyl is an alkyl radical having 1 to 4 carbon atoms, and R 5 is H, alkyl, an amino acid radical, 5 dipeptide radical or tripeptide radical and b) one or more substances chosen from enzymes, 10 vitamins and vitamin derivatives, for the preparation of a cosmetic formulation.
10. Use according to claim 9 for the care and/or prophylaxis of dry and/or flaky skin. 15
11. Use according to claim 9 for the protection of human skin against dryness and/or high salt concentrations. 20
12. Use according to claim 9 for the protection of cells, proteins and/or biomembranes of human skin.
13. Use according to claim 9 for the protection of the microflora of the human skin. 25
14. Use according to claim 9 for stabilizing the skin barrier.
15. Use of one or more compounds chosen from the 30 compounds of the formulae Ia and Ib, the physiologically compatible salts of the compounds of the formulae Ia and Ib and the stereoisomeric forms of the compounds of the formulae Ia and Ib and one or more substances chosen from enzymes, 35 vitamins and vitamin derivatives according to claim 9, characterized in that the cosmetic formulation is in the form of a solution, a suspension, an emulsion, a paste, an ointment, a WO 00/07559 PCT/EP99/05238 - 33 gel, a cream, a lotion, a powder, a soap, a surfactant-containing cleansing preparation, an oil, a lipstick, a lipcare stick, a mascara, an eyeliner, eyeshadows, blusher, a powder, emulsion 5 or wax foundation, a sunscreen, presun and aftersun preparation or a spray.
16. Use according to one of claims 10 to 14, characterized in that one or more compounds chosen 10 from the compounds of the formulae Ia and Ib, the physiologically compatible salts of the compounds of the formulae Ia and Ib and the stereoisomeric forms of the compounds of the formulae Ia and Ib and one or more substances chosen from enzymes, 15 vitamins and vitamin derivatives for external application in the form of a solution, a suspension, an emulsion, a paste, an ointment, a gel, a ,cream, a lotion, a powder, a soap, a surfactant-containing cleansing preparation, an 20 oil, a lipstick, a lipcare stick, a mascara, an eyeliner, eyeshadows, blusher, a powder, emulsion or wax foundation, a sunscreen, presun and aftersun preparation or a spray. 25
17. Use according to one of claims 8 to 16, character ized in that the compounds of the formulae Ia and Ib are chosen from the compounds (S)-1,4,5,6 tetrahydro-2-methyl-4-pyrimidinecarboxylic acid and (S,S)-1,4,5, 6-tetrahydro-5-hydroxy-2-methyl-4 30 pyrimidinecarboxylic acid.
18. Use according to one of claims 8 to 17, characterized in that that the enzymes are chosen from superoxide dismutase, protease, lipase, 35 pepsin, trypsin, chymotrypsin, elastase, diastase, catalase, dehydrogenase, urease, lysozyme, neuraminidase, peroxidase, glutathionee peroxidase, phosphatase, dismutase, papain, WO 00/07559 PCT/EP99/05238 - 34 bromelain, alcalase, aminopeptidase K, aminopeptidase M, carboxypeptidase A, carboxypeptidase B, carboxypeptidase Y, clostripain, collagenase, ficine, leucine 5 amidepeptidase, lytic enzyme, pronase E and proteinase K.
19. Use according to one of claims 8 to 18, characterized in that the vitamins and/or vitamin 10 derivatives are chosen from vitamin A, vitamin A propionate, vitamin A palmitate, vitamin A acetate, retinol, vitamin B, thiamine chloride hydrochloride, riboflavin, nicotinamide, vitamin C, vitamin D, ergocalciferol, vitamin E, DL-a 15 tocopherol, tocopherol E acetate, tocopherol hydrogensuccinate, vitamin K 1 , esculin, thiamine, nicotinic acid, pyridoxine, pyridoxal, pyridoxamine, panthothenic acid, biotin, folic acid and cobalamin. 20
20. Method of preparing a cosmetic formulation, characterized in that a) one or more compounds chosen from compounds of 25 the formulae Ia and Ib R 3 R N Rla H Rz HN-(C-R )n b R N R2lb WO 00/07559 PCT/EP99/05238 - 35 the physiologically compatible salts of the compounds of the formulae Ia and Ib, and the stereoisomeric forms of the compounds of the 5 formulae Ia and Ib, where Ri is H or alkyl, R2 is H, COOH, COO-alkyl or CO-NH-R 5 , 10 R 3 and R 4 are in each case independently of one another H or OH, n is 1, 2 or 3, 15 alkyl is an alkyl radical having 1 to 4 carbon atoms, and Rs 5 is H, alkyl, an amino acid radical, dipeptide radical or tripeptide radical 20 and b) one or more substances chosen from enzymes, vitamins and vitamin derivatives 25 optionally with auxiliaries and/or carriers are converted to a suitable cosmetic formulation form.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19834818 | 1998-08-01 | ||
DE19834818A DE19834818A1 (en) | 1998-08-01 | 1998-08-01 | Cosmetic formulation |
PCT/EP1999/005238 WO2000007559A1 (en) | 1998-08-01 | 1999-07-22 | Cosmetic formulation containing ectoine derivatives, enzymes, vitamins and/or vitamin derivatives |
Publications (2)
Publication Number | Publication Date |
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AU5163199A true AU5163199A (en) | 2000-02-28 |
AU751968B2 AU751968B2 (en) | 2002-09-05 |
Family
ID=7876167
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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AU51631/99A Ceased AU751968B2 (en) | 1998-08-01 | 1999-07-22 | Cosmetic formulation containing ectoine derivatives, enzymes, vitamins and/or vitamin derivatives |
Country Status (6)
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EP (1) | EP1100453B1 (en) |
JP (1) | JP2002522367A (en) |
AU (1) | AU751968B2 (en) |
DE (2) | DE19834818A1 (en) |
ES (1) | ES2235498T3 (en) |
WO (1) | WO2000007559A1 (en) |
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DE10003786A1 (en) * | 2000-01-28 | 2001-08-02 | Merck Patent Gmbh | Galenic formulation |
DE10014632A1 (en) * | 2000-03-24 | 2001-09-27 | Merck Patent Gmbh | Protection of stress proteins in the skin using ectoine or its derivatives, is useful in topical skin care or make-up cosmetic compositions for maintaining the defense mechanism of the skin |
US7048910B2 (en) | 2000-09-07 | 2006-05-23 | Merck Patent Gmbh | Use of ectoine or ectoine derivatives for oral care |
CN1198579C (en) * | 2000-09-13 | 2005-04-27 | 宝洁公司 | Cosmetic method |
MXPA03002168A (en) * | 2000-09-13 | 2003-07-24 | Procter & Gamble | Cosmetic method. |
CN1612722A (en) * | 2001-11-13 | 2005-05-04 | 宝洁公司 | Compositions containing enzymes stabilized with certain osmo-protectants and methods for using such compositions in personal care |
DE10214257A1 (en) | 2002-03-28 | 2003-10-16 | Merck Patent Gmbh | Use of compatible solutes to inhibit the release of ceramides |
DE10242748A1 (en) * | 2002-09-13 | 2004-03-18 | Henkel Kgaa | Hair treatment uses a combination of a dinitrogen-containing heterocyclic compound, especially ectoin, with a vitamin, provitamin, alkylpolyglucoside, allantoin, bisabolol or derivative |
DE102004049062A1 (en) * | 2004-03-30 | 2005-10-13 | bitop Aktiengesellschaft für biotechnische Optimierung | Topical preparation for application on the skin containing natural oil of the evening primrose (Oenothera biennis) (= Oleum Oenothera) and osmolytes from extremophilic microorganisms |
DE102010023324A1 (en) * | 2010-06-10 | 2011-12-15 | Thomas Schütz | Use of corrinoids for cosmetic application in healthy coat or healthy skin, and for cosmetic care in coat and skin diseases in small and large animals (warm and cold-blooded), (eg in fish, birds, horses, cattle, camels, Dogs cats, reptiles) |
TW201309334A (en) * | 2011-02-25 | 2013-03-01 | Shiseido Co Ltd | Stratum corneum peeling accelerator |
US20200030214A1 (en) * | 2017-03-06 | 2020-01-30 | Merck Patent Gmbh | Use of compatible solutes |
JP2022543068A (en) | 2019-08-01 | 2022-10-07 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | Prevention and reduction of keratinization disorders and related cosmetic agents |
CN111840307B (en) * | 2020-08-18 | 2023-09-12 | 华熙生物科技股份有限公司 | Composition with effects of easing pain, relieving itching and removing dampness and rash |
CN115252445B (en) * | 2022-07-14 | 2024-03-05 | 苏州猫尔科技有限公司 | Composite microecological oil-control hair care composition and hair care product |
Family Cites Families (6)
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DE2614723C2 (en) * | 1976-04-06 | 1986-01-02 | Wella Ag, 6100 Darmstadt | Cosmetic agent |
DE2746650A1 (en) * | 1977-10-17 | 1979-04-26 | Henkel Kgaa | Skin care, protection and cleansing compsns. - contain imidazolidine-2-one or derivs. as moisture retainers or restorer |
US4529587A (en) * | 1982-02-19 | 1985-07-16 | Lever Brothers Company | Method of reducing sebum on the hair and skin |
CA2132289A1 (en) * | 1993-10-12 | 1995-04-13 | Bharat Desai | Higher purity imidazoline based amphoacetate surfactants and processes for the preparation thereof |
DE4342560A1 (en) * | 1993-12-14 | 1995-06-22 | Marbert Gmbh | Use of 1,4,5,6-tetra:hydro-4-pyrimidine carboxylic acid derivs. in cosmetics |
JPH09143167A (en) * | 1995-11-17 | 1997-06-03 | Dainippon Pharmaceut Co Ltd | Stabilization of enzyme |
-
1998
- 1998-08-01 DE DE19834818A patent/DE19834818A1/en not_active Withdrawn
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1999
- 1999-07-22 ES ES99936589T patent/ES2235498T3/en not_active Expired - Lifetime
- 1999-07-22 DE DE59911412T patent/DE59911412D1/en not_active Expired - Lifetime
- 1999-07-22 AU AU51631/99A patent/AU751968B2/en not_active Ceased
- 1999-07-22 JP JP2000563245A patent/JP2002522367A/en active Pending
- 1999-07-22 WO PCT/EP1999/005238 patent/WO2000007559A1/en active IP Right Grant
- 1999-07-22 EP EP99936589A patent/EP1100453B1/en not_active Expired - Lifetime
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EP1100453B1 (en) | 2005-01-05 |
DE59911412D1 (en) | 2005-02-10 |
WO2000007559A1 (en) | 2000-02-17 |
AU751968B2 (en) | 2002-09-05 |
DE19834818A1 (en) | 2000-02-03 |
ES2235498T3 (en) | 2005-07-01 |
JP2002522367A (en) | 2002-07-23 |
EP1100453A1 (en) | 2001-05-23 |
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