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EP1311237A2 - Use of cyclic 2,4-diphosphoglycerates (cdgp) and/or derivatives thereof in cosmetic and dermatological formulations - Google Patents

Use of cyclic 2,4-diphosphoglycerates (cdgp) and/or derivatives thereof in cosmetic and dermatological formulations

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Publication number
EP1311237A2
EP1311237A2 EP01976086A EP01976086A EP1311237A2 EP 1311237 A2 EP1311237 A2 EP 1311237A2 EP 01976086 A EP01976086 A EP 01976086A EP 01976086 A EP01976086 A EP 01976086A EP 1311237 A2 EP1311237 A2 EP 1311237A2
Authority
EP
European Patent Office
Prior art keywords
compounds
formula
formulation according
human skin
formulation
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP01976086A
Other languages
German (de)
French (fr)
Inventor
Thomas Schwarz
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bitop Gesellschaft fur Biotechnische Optimierung mbH
Original Assignee
Bitop Gesellschaft fur Biotechnische Optimierung mbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Bitop Gesellschaft fur Biotechnische Optimierung mbH filed Critical Bitop Gesellschaft fur Biotechnische Optimierung mbH
Publication of EP1311237A2 publication Critical patent/EP1311237A2/en
Withdrawn legal-status Critical Current

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Classifications

    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/14—Liposomes; Vesicles
    • 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
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A61K8/27—Zinc; Compounds thereof
    • 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
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/37—Esters of carboxylic acids
    • A61K8/375—Esters of carboxylic acids the alcohol moiety containing more than one hydroxy group
    • 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
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
    • 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
    • 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
    • A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
    • A61K8/4913—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having five membered rings, e.g. pyrrolidone carboxylic acid
    • 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
    • A61K8/55—Phosphorus compounds
    • 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
    • A61K8/65—Collagen; Gelatin; Keratin; Derivatives or degradation products thereof
    • 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
    • A61K8/678—Tocopherol, i.e. vitamin E
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/16—Emollients or protectives, e.g. against radiation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • 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
    • 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
    • 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
    • A61Q19/001—Preparations for care of the lips
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A61Q5/02—Preparations for cleaning the hair
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A61Q5/06—Preparations for styling the hair, e.g. by temporary shaping or colouring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A61Q5/12—Preparations containing hair conditioners

Definitions

  • cyclic 2.4 diphosphoglycerate cDGP
  • cDGP cyclic 2.4 diphosphoglycerate
  • the invention relates to the use of one or more chemical compounds selected from the compounds of the formulas Ia (cyclic diphosphoglycerate) in cosmetic and dermatological formulations.
  • the invention relates e.g. the production of a cosmetic or dermatological formulation for protecting and stabilizing human skin cells and their organic components, such as Proteins, enzymes, membranes, nucleic acids or antioxidants.
  • the invention includes the use of physiologically compatible salts of the compounds Ia and Ib, the stereoisomeric forms of the compounds of the formulas Ia and Ib and derivatives of these compounds (for example esters) for use in cosmetic and dermatological formulations. Due to their origin from extremophilic microorganisms, which effectively protect themselves by the production of new compatible solutes such as cyclic diphosphoglycerate from environmental stress situations such as UV radiation, heat, radicals, cold, drought or osmotic or chemical stress, and only survive in this way, these substances represent a completely new way of protecting organisms and their components from damaging environmental influences.
  • the cell's own repair systems DNA repair after UV damage, induction and stabilization of the chaperon proteins for refolding (partially) denatured proteins and enzymes
  • DNA repair after UV damage, induction and stabilization of the chaperon proteins for refolding (partially) denatured proteins and enzymes can be stabilized and activated for the first time using cyclic diphosphoglycerate.
  • the maintenance of the cell's antioxidative potential protein and DNA damage by free radicals, lipid oxidation of the cell membranes is ensured for the first time by cyclic diphosphoglycerate.
  • cyclic diphosphoglycerates pass through several skin layers into the interior of the target cells and, as co-solvents or penetration enhancers, can bring other active ingredients from the cosmetic formulation (e.g. proteins, enzymes, vitamins, antioxidants) to their actual destination.
  • active ingredients e.g. proteins, enzymes, vitamins, antioxidants
  • Cyclic diphosphoglycerate Due to its chemical structure, cyclic diphosphoglycerate is compatible with the majority of the usual cosmetic basic formulations, and further modifications to the suitable form of application are possible by appropriate modifications of the functional side chains. Cyclic diphosphoglycerate is moisturizing due to the large number of hydroxyl groups and gives a pleasant feeling on the skin.
  • Compatible solutes act as natural solvents in extremophilic microorganisms and stabilize enzymes, proteins and other cell components by generating a more native, globular state that not only protects the proteins from proteolysis, but also keeps them in a more compact and active state.
  • Cyclic is used as a co-solvent or penetration enhancer for cosmetic active ingredients
  • Diphosphoglycerate can be used in a wide range, particularly with regard to the possible derivatization of individual functional groups.
  • the invention thus relates to the use of cyclic diphosphoglycerate as an additive and active ingredient with a completely new mode of action in cosmetic and dermatological preparations and products.
  • UV filters Today's skin and sunscreen products include two classes of UV filters. Physically effective UV filters consist of inorganic compounds (e.g. titanium dioxide) that reflect the light that hits the skin. Chemically acting organic molecules absorb UV light of the wavelengths that are responsible for the formation of erythema (sunburn) (primarily 295 to 323 nm with a maximum at 308 nm).
  • inorganic compounds e.g. titanium dioxide
  • chemically acting organic molecules absorb UV light of the wavelengths that are responsible for the formation of erythema (sunburn) (primarily 295 to 323 nm with a maximum at 308 nm).
  • radical scavengers and antioxidants are used as additives in cosmetic formulations to protect against oxidative stress, which is caused by environmental influences (UV radiation, smoke, chemical substances) but also by the cell's own activities.
  • the range of active ingredients covers both water-soluble radical scavengers (e.g. ascorbic acid), which act in the interior of the liquid, and fat-soluble antioxidants (e.g. retionol palmitate or ⁇ -tocopherol), which Membrane structures take effect. It is rarely taken into account that with topical applications of these active ingredients, at most 3% reach a deeper skin layer and the rest remains ineffective on the skin surface.
  • Hyperthermophiles are very unusual microorganisms because they grow optimally at temperatures (60-110 ° C), which would lead to massive damage to cellular structures in mesophilic ("normal") organisms.
  • a large amount of research has therefore been carried out to determine the Identify biochemical components that lead to the remarkable thermal, chemical and physical stabilization of cell structures, with the focus of the research work on the isolation of thermostable enzymes, since numerous enzymatically catalyzed industrial processes take place under extreme environmental conditions and suitable biocatalysts are sought.
  • many enzymes from hyperthermophilic microorganisms are stable even at high temperatures, this does not generally apply to the cellular structures of thermo- and hyperthermophilic organisms.
  • thermophilic microorganisms Low molecular weight organic substances (compatible solutes, "hypersolutes") in the intracellular milieu make a significant contribution to the high temperature stability of cell structures.
  • Various novel hypersolutes have been identified in hyperthermophilic microorganisms in recent years. In some cases, the contribution of these compounds to Protection of cellular structures - especially enzymes - against heat and drought has already been impressively demonstrated, bitop has developed technologies for the production of compatible solutes from thermophilic microorganisms.
  • the human skin is an organ that protects the body from external influences with various types of specialized cell types - the keratinocytes, melanocytes, Langerhans cells, Merkel cells and embedded sensory cells.
  • the external physical influences include thermal and mechanical influences as well as the effect of radiation, e.g. UV, VIS, and IR radiation, count.
  • External chemical influences are to be understood in particular as the effects of toxins, allergens and substances which bind to the deoxyribonucleic acid.
  • the external biological influences include the effects of foreign organisms and their metabolic products.
  • Sunburn erythema solare
  • UV-A radiation has a comparatively minor influence on its formation.
  • Sunburn can range from a light tint to a severe burn with blistering. Since these episodes no earlier than 4-6 h after the radiation occurs, it is too late for countermeasures. Multiple sunburns - especially in childhood - significantly increase the risk of skin cancer.
  • the causes for this are damage, in particular the nucleic acids of human skin cells and a faulty repair of the damaged deoxyribonucleic acid in the cell nucleus, as well as probably the immunosuppressive effect of UV radiation, ie the weakening of the immune response by UV radiation.
  • Excessive UV-A and UV-B exposure contributes to skin aging or light aging, for example in the form of structural changes in the connective tissue (actinic elastosis).
  • Excessive UV-B exposure is the main cause of chronic skin changes.
  • Each tissue has an antioxidative potential (AOP) made up of enzymatic and non-enzymatic antioxidants, which keep the content of prooxidants below a limit value in unstressed cells, which is harmless to the healthy cell. If these natural antioxidants are inactivated or denatured, the skin's resistance and regeneration ability is significantly reduced.
  • AOP antioxidative potential
  • Extremophilic microorganisms thermophiles and hyperthermophiles protect themselves from thermal stress through the formation of cyclic diphosphoglycerate. In the presence of these substances it is therefore possible for these microbial organisms to exist under the prevailing extreme conditions, since cyclic diphosphoglycerate stabilizes the metabolism and the essential organic components and protects against damage.
  • cyclic diphosphoglycerate also shows the stabilizing effects on human skin and thus represents an ideal active ingredient and additive for cosmetic and dermatological preparations.
  • Cyclic diphosphoglycerate thus represents a universally applicable and completely new protective principle in cosmetics and dermatology.
  • the above-mentioned problem is selected by using one or more compounds from the compounds of the formulas la (cyclic diphosphoglycerate) in cosmetic and dermatological formulations solved.
  • the invention relates to Use of one or more compounds selected from the compounds of the formula Ia (cyclic diphosphoglycerate),
  • physiologically tolerable salts of the compound la the stereoisomeric forms of the compounds of the formula la and derivatives for the preparation of a cosmetic or dermatological formulation for protecting and stabilizing human skin cells and their organic constituents, e.g. Proteins, enzymes, membranes, nucleic acids or antioxidants.
  • Possible salts are the alkali and alkaline earth salts, but especially the Na and K salts.
  • the esters which can be used are the esters of physiologically acceptable alcohols, in particular C 1 -C 4 alcohols, such as methanol, ethanol, propanols or butanols.
  • the invention relates in particular to the use of one or more compounds selected from the compounds of the formula Ia, the physiologically tolerable salts of the compounds of the formula Ia and the stereoisomeric forms of the compounds of the formula Ia for the production of a cosmetic or dermatological formulation for protecting and stabilizing the human skin cells and their organic components such as proteins, enzymes, membranes, nucleic acids, antioxidants etc. from physical, chemical and biological influences such as from radiation (UV, IR, VIS radiation), from denaturing substances, from temperature or from cold.
  • the present invention describes this principle of protection for the first time.
  • the possible uses are very diverse and can only be described by way of example within the scope of the invention. However, the invention is not intended to be limited by giving examples.
  • Membranes represent the natural barrier of cells and cell organelles to the surrounding medium. The membranes make it possible to ensure a constant internal environment in the individual cells or cell components. Biological membranes are multi-component systems that generally consist of lipids, cholesterol and proteins. The exact composition of individual membranes is subject to varying fluctuations depending on their origin. However, elementary components of membranes are lipids and proteins.
  • Lipids can be divided into the so-called “simple” lipids such as fats and waxes and “complex” lipids.
  • phosphoric acid diesters in which the glycerol residue generally is condensed with saturated (R1) and unsaturated (R2) fatty acids.
  • the phosphoric acid residue is additionally condensed with a component of alcoholic structure such as inositol or ethanolamine (R3).
  • glycerophospholipids Due to their ambivalent structure with a hydrophilic phosphate residue and lipophilic fatty acid residues, glycerophospholipids are able to in water Solution to form aggregates (eg double layers or micelles) in which the only hydrophilic phosphate residue comes into contact with the aqueous phase. This structure is also found in the form of closed lamellar vesicles, the so-called liposomes.
  • the following figure shows an example of the group of lipids with two phosphodiester groups, the so-called diphosphatidylglycerols (cardiolipins):
  • DIP Determination of a phosphate anion: stabilization of protein side chains via ionic and van der Waals interactions. Furthermore DIP is characterized by the following features:
  • cDPG is the cell's natural solvent.
  • biogenic substances have to be solubilized. No data on the toxicity of the substance are available to date.
  • the intracellular concentration of cDPG within the cell is over 300 mM, so that a high level of biocompatibility can also be expected here!
  • cDPG has very good protective properties in the thermally induced denaturation of enzymes, some of which are better in comparison to other compatible solutes.
  • LDH freezing protein solutions
  • the commercial application of the invention is in the entire field of cosmetic and dermatological products and as research reagents in the field of cosmetic and dermatological development.
  • the cosmetic and dermatological formulations are prepared by one or more compounds of the formula la (cyclic diphosphoglycerate), the physiologically tolerable salts of the compounds of the formula la, the stereoisomeric forms of the compound of the formula la or derivatives, optionally with auxiliaries and / or carriers be brought into a suitable formulation.
  • the auxiliaries and carriers come from the group of carriers, preservatives and other customary auxiliaries.
  • the compounds of the formula la (cyclic diphosphoglycerate) contained in cosmetic and dermatological formulations, the physiologically tolerable salts of the compounds of the formula la and the stereoisomeric forms of the compounds of the formula la are used externally.
  • solutions, suspensions, emulsions, pastes, ointments, gels, creams, lotions, powders, soaps, surfactant-containing cleaning preparations, oils and sprays can be added to the formulations.
  • Preferred additives come from the group of preservatives, antioxidants, stabilizers, solubilizers, vitamins, colorants and odor improvers.
  • ointments, pastes, creams and gels can contain the usual 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 these substances.
  • 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 these substances.
  • powders and sprays can contain the usual blowing agents, for example chlorofluorocarbons, propane / butane or dimethyl ether, in addition to the customary carriers.
  • solutions and emulsions can additionally contain the customary carriers, such as solvents, solubilizers and emulsifiers or oils.
  • suspensions can contain additional carriers such as e.g. Contain water or ethanol.
  • the proportion of the compound of the formula Ia (cyclic diphosphoglycerate), the physiologically tolerable salts of the compounds IA, and the stereoisomeric forms of the compounds of the formula IA cosmetic and dermatological formulations is preferably from 0.0001 to 50% by weight, particularly preferably from 0.001 to 10 % By weight based on the entire cosmetic formulation.
  • cyclic diphosphoglycerate supports e.g. through the proven stabilization against thermal protein denaturation and inactivation the cell's own antioxidative potential. Damage caused by radicals is thus counteracted. Due to the proven DNA protection of compatible solutes and their protein-stabilizing effect, the use of cyclic diphosphoglycerate according to the invention represents a new type of active sun protection (e.g. UV and IR radiation) in cosmetics and dermatology.
  • active sun protection e.g. UV and IR radiation
  • a lotion (O / W) according to the invention containing cyclic diphosphoglycerate is produced from the following components:
  • a cream (O / W) according to the invention containing cyclic diphosphoglycerate is produced from the following components:
  • An inventive liposome-containing gel containing cyclic diphosphoglycerate is produced from the following components:
  • An inventive gel (O / W) containing cyclic diphosphoglycerate is produced from the following components:
  • a sunscreen emulsion according to the invention containing cyclic diphosphoglycerate is produced from the following components:
  • Example sun lotion 0.05% propyl hydroxybenzoate or 0.15% methyl 4-hydroxybenzoate can be used as a preservative.
  • Example sun lotion 0.05% propyl hydroxybenzoate or 0.15% methyl 4-hydroxybenzoate can be used as a preservative.
  • An emulsifier-free sun lotion SPF 30 (W / O) containing cyclic diphosphoglycerate is produced from the following components:
  • a hair tonic according to the invention containing cyclic diphosphoglycerate is produced from the following components:
  • a spray formulation according to the invention containing cyclic diphosphoglycerate is produced from the following components:

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Abstract

The invention relates to the inclusion of the low molecular weight substance (compatible solute), cyclic 2,4-diphosphoglycerate (cDGP), from extremophilic micro-organisms and/or derivatives of said compound, for example, an acid, a salt, or an ester, in cosmetic or dermatological formulations for protection of the skin from environmental influences and to increase the regeneration capacity. According to the invention, cyclic 2,4-diphosphoglycerate is implicated in active cell protection of the endogenous cell radical traps, antioxidants, the DNA, cell membranes and further cell compartments, by means of a protective effect of the above, against damaging environmental effects, for example, UV radiation, IR radiation, and environmental stress (thermal, chemical and physical). The compatible solute may serve as co-solvent and penetration improver for other active ingredients added to the cosmetic formulation, in order to not only stabilise the above in the cosmetic formulation, but also for active transport into deeper skin layers.

Description

Verwendung von cvclischem 2.4 Diphosphoglycerat (cDGP) und/oder Derivaten in kosmetischen und dermatoloqischen Formulierungen Use of cyclic 2.4 diphosphoglycerate (cDGP) and / or derivatives in cosmetic and dermatological formulations
Technisches Gebiet / Gegenstand der ErfindungTechnical field / subject of the invention
Gegenstand der Erfindung ist die Verwendung einer oder mehrerer chemischen Verbindungen ausgewählt aus den Verbindungen der Formeln la (cyclisches Diphosphoglycerat) in kosmetischen und dermatologischen Formulierungen. Die Erfindung betrifft z.B. die Herstellung einer kosmetischen oder dermatologischen Formulierung zum Schutz und zur Stabilisierung der menschlichen Hautzellen sowie deren organischer Bestandteile wie z.B. Proteine, Enzyme, Membranen, Nukleinsäuren oder Antioxidantien.The invention relates to the use of one or more chemical compounds selected from the compounds of the formulas Ia (cyclic diphosphoglycerate) in cosmetic and dermatological formulations. The invention relates e.g. the production of a cosmetic or dermatological formulation for protecting and stabilizing human skin cells and their organic components, such as Proteins, enzymes, membranes, nucleic acids or antioxidants.
Die Erfindung schließt die Verwendung von physiologisch verträglichen Salzen der Verbindungen la und Ib, den stereoisomeren Formen der Verbindungen der Formeln la und Ib und Derivate dieser Verbindungen (z.B. Ester) zur Verwendung in kosmetischen und dermatologischen Formulierungen mit ein. Durch ihre Herkunft aus extremophilen Mikroorganismen, die sich durch die Produktion von neuartigen kompatiblen Soluten wie cyclisches Diphosphoglycerat vor umweltbedingten Stresssituationen, wie UV-Strahlung, Wärme, Radikalen, Kälte, Trockenheit oder osmotischem oder chemischem Stress, effektiv schützen und nur auf diese Weise überleben, stellen diese Substanzen einen völlig neuen Weg zum Schutz von Organismen und deren Komponenten vor schädigenden Umwelteinflüssen dar.The invention includes the use of physiologically compatible salts of the compounds Ia and Ib, the stereoisomeric forms of the compounds of the formulas Ia and Ib and derivatives of these compounds (for example esters) for use in cosmetic and dermatological formulations. Due to their origin from extremophilic microorganisms, which effectively protect themselves by the production of new compatible solutes such as cyclic diphosphoglycerate from environmental stress situations such as UV radiation, heat, radicals, cold, drought or osmotic or chemical stress, and only survive in this way, these substances represent a completely new way of protecting organisms and their components from damaging environmental influences.
Zelleigene Reparatursysteme (DNA-Reparatur nach UV-Schädigung, Induktion und Stabilisierung der chaperon-Proteine zur Neufaltung (teil-)denaturierter Proteine und Enzyme) können erstmals durch cyclisches Diphosphoglycerat stabilisiert und aktiviert werden. Die Aufrechterhaltung des antioxidativen Potentials der Zelle (Protein- und DNA-Schädigung durch freie Radikale, Lipidoxidation der Zellmembranen) wird erstmals durch cyclisches Diphosphoglycerat gewährleistet.The cell's own repair systems (DNA repair after UV damage, induction and stabilization of the chaperon proteins for refolding (partially) denatured proteins and enzymes) can be stabilized and activated for the first time using cyclic diphosphoglycerate. The maintenance of the cell's antioxidative potential (protein and DNA damage by free radicals, lipid oxidation of the cell membranes) is ensured for the first time by cyclic diphosphoglycerate.
Durch ihr geringes Molekulargewicht gelangen cyclisches Diphosphoglycerate durch mehrere Hautschichten bis ins Innere der Zielzellen und können als Co-Solventien oder Penetrationsverstärker andere Wirkstoffe aus der kosmetischen Formulierung (z.B. Proteine, Enzyme, Vitamine, Antioxydantien) mit an den eigentlichen Bestimmungsort bringen.Due to their low molecular weight, cyclic diphosphoglycerates pass through several skin layers into the interior of the target cells and, as co-solvents or penetration enhancers, can bring other active ingredients from the cosmetic formulation (e.g. proteins, enzymes, vitamins, antioxidants) to their actual destination.
Aufgrund seiner chemischen Struktur ist cyclisches Diphosphoglycerat mit der Mehrzahl der üblichen kosmetischen Grundformulierungen verträglich und durch entsprechende Modifikationen der funktioneilen Seitenketten sind weitere Anpassungen an die geeignete Applikationsform möglich. Dabei wirkt cyclisches Diphosphoglycerat durch die Vielzahl der Hydroxygruppen feuchtigkeitsspendend und vermitteln ein angenehmes Hautgefühl.Due to its chemical structure, cyclic diphosphoglycerate is compatible with the majority of the usual cosmetic basic formulations, and further modifications to the suitable form of application are possible by appropriate modifications of the functional side chains. Cyclic diphosphoglycerate is moisturizing due to the large number of hydroxyl groups and gives a pleasant feeling on the skin.
Kompatible Solute wirken als natürliche Lösungsmittel in extremophilen Mikroorganismen und stabilisieren Enzyme, Proteine und andere Zellbestandteile durch die Generierung eines nativeren, globuläreren Zustandes, der die Proteine nicht nur vor Proteolyse schützt, sondern diese auch in einem kompakteren und aktiveren Zustand hält. Als Co-Solvens oder Penetrationsverstärker für kosmetische Wirkstoffe ist cyclisches Diphosphoglycerat besonders im Hinblick auf eine mögliche Derivatisierung einzelner funktioneller Gruppen in einem weiten Feld einsetzbar.Compatible solutes act as natural solvents in extremophilic microorganisms and stabilize enzymes, proteins and other cell components by generating a more native, globular state that not only protects the proteins from proteolysis, but also keeps them in a more compact and active state. Cyclic is used as a co-solvent or penetration enhancer for cosmetic active ingredients Diphosphoglycerate can be used in a wide range, particularly with regard to the possible derivatization of individual functional groups.
Gegenstand der Erfindung ist somit die Verwendung von cyclisches Diphosphoglycerat als Additiv und Wirkstoff mit einem völlig neuartigen Wirkprinzip in kosmetischen und dermatologischen Präparaten und Produkten.The invention thus relates to the use of cyclic diphosphoglycerate as an additive and active ingredient with a completely new mode of action in cosmetic and dermatological preparations and products.
Stand der TechnikState of the art
Sonnenschutzsun protection
Heutige Haut- und Sonnenschutzmittel beinhalten zwei Klassen von UV-Filtern. Physikalisch wirksame UV-Filter bestehen aus anorganischen Verbindungen (z.B. Titandioxid), die das auftreffende Licht auf der Haut reflektieren. Chemisch wirkende organische Moleküle absorbieren UV-Licht der Wellenlängen, die für die Ausbildung von Erythemen (Sonnenbrand) verantwortlich sind (vornehmlich 295 bis 323 nm mit einem Maximum bei 308 nm).Today's skin and sunscreen products include two classes of UV filters. Physically effective UV filters consist of inorganic compounds (e.g. titanium dioxide) that reflect the light that hits the skin. Chemically acting organic molecules absorb UV light of the wavelengths that are responsible for the formation of erythema (sunburn) (primarily 295 to 323 nm with a maximum at 308 nm).
Somit sind alle bisherigen Sonnenschutzpräparate reine „Sonnenbrandverminderer", die nur dem dramatischen, für den Menschen leicht ersichtlichen Effekt der Hautschädigung vorbeugen. In der Literatur wird aber bereits vor den wesentlich gefährlicheren Zellschädigungen gewarnt, die im Vorfeld eines Erythems wirksam werden, wie der massiven DNA-Schädigung, die bis zur Ausbildung eines Melanoms entarten kann.Thus, all previous sunscreen preparations are pure "sunburn reducers" that only prevent the dramatic effect of skin damage that is easy to see for humans. However, the literature warns against the much more dangerous cell damage that takes effect before erythema, such as massive DNA -Damage that can degenerate into melanoma.
Schutz vor oxidativem Stress, Radikalen u. UmweltchemikalienProtection against oxidative stress, radicals and. environmental chemicals
Im Bereich der Kosmetik finden eine Vielzahl von Radikalfängern und Antioxidantien als Zusatzstoffe in kosmetischen Formulierungen ihre Anwendung zum Schutz vor oxidativem Stress, der durch Umwelteinflüsse (UV-Strahlung, Rauch, chemische Substanzen) aber auch durch zelleigene Aktivitäten entsteht. Die Wirkstoffpalette deckt sowohl wasserlösliche Radikalfänger (z.B. Ascorbinsäure), die im flüssigen Zellinneren wirken, wie auch fettlösliche Antioxidantien (z.B. Retionolpalmitat oder σ-Tocopherol), die in Membranstrukturen wirksam werden, ab. Dabei wird nur selten bedacht, daß bei topischen Applikationen dieser Wirkstoffe höchstens 3% eine tiefere Hautschicht erreichen und der Rest unwirksam an der Hautoberfläche verbleibt.In the field of cosmetics, a large number of radical scavengers and antioxidants are used as additives in cosmetic formulations to protect against oxidative stress, which is caused by environmental influences (UV radiation, smoke, chemical substances) but also by the cell's own activities. The range of active ingredients covers both water-soluble radical scavengers (e.g. ascorbic acid), which act in the interior of the liquid, and fat-soluble antioxidants (e.g. retionol palmitate or σ-tocopherol), which Membrane structures take effect. It is rarely taken into account that with topical applications of these active ingredients, at most 3% reach a deeper skin layer and the rest remains ineffective on the skin surface.
Cosolventiencosolvents
Die menschliche Haut besteht zum Schutz vor schädigenden Umwelteinflüssen aus mehreren Schichten (Stratum corneum, Subdermis, Dermis, Epidermis), die eine praktisch undurchdringliche Barriere für Fremdstoffe darstellt. Mögliche Penetrationswege für kosmetische Wirkstoffe sind interzellulär (nur für kleine polare und unpolare Stoffe durch laterale Diffusion durch die hochorganisierten interzellulären Lipidschichten möglich), intrazellulär oder transfollikulär (Liposomentechnologie). Nachweislich gelangen jedoch selbst mit der fortschrittlichen Liposomenverkapselung in Nanopartikel kosmetische Wirkstoffe nur zu einem extrem geringen Prozentsatz (<3%) durch die oberen Hautschichten zu ihrem eigentlichen Zielbestimmungsort, wo sie ihre schützende Wirkung erst entfalten sollen. Größere Moleküle, wie die in ihrer potentiellen Wirkung vielversprechenden Enzyme (z.B. Sericin, Kollytin, Glutathion-S-Transferase oder die Gruppe der Cytokine), sind durch die sterische Hinderung praktisch selbst mit modernsten Methoden nur minimal in lebende Zellen einzuschleusen.To protect against damaging environmental influences, human skin consists of several layers (stratum corneum, subdermis, dermis, epidermis), which represents a practically impenetrable barrier to foreign substances. Possible penetration paths for cosmetic active substances are intercellular (only possible for small polar and nonpolar substances through lateral diffusion through the highly organized intercellular lipid layers), intracellularly or transfollicularly (liposome technology). However, even with the advanced encapsulation of liposomes in nanoparticles, it has been proven that only an extremely small percentage (<3%) of cosmetic active ingredients reach their actual destination through the upper skin layers, where they are only supposed to develop their protective effect. Larger molecules, such as the promising enzymes with potential effects (e.g. sericin, klytin, glutathione-S-transferase or the group of cytokines), can only be minimally introduced into living cells due to the steric hindrance, even with the most modern methods.
Kompatible Solute und HyperthermophileCompatible solutes and hyperthermophiles
Hyperthermophile sind sehr außergewöhnliche Mikroorganismen, da sie optimal bei Temperaturen (60-110°C) wachsen, die bei mesophilen („normalen") Organismen zu massiven Schädigungen zellulärer Strukturen führen würden. In den letzten Jahren wurde daher ein großer Forschungsaufwand betrieben, um die biochemischen Komponenten zu identifizieren, die zu der bemerkenswerten thermischen, chemischen und physikalischen Stabilisierung der Zellstrukturen führt. Der Schwerpunkt der Forschungsarbeiten lag hierbei auf der Isolierung thermostabiler Enzyme, da zahlreiche enzymatisch katalysierte industrielle Prozesse unter extremen Milieubedingungen ablaufen und hierfür geeignete Biokatalysatoren gesucht werden. Obwohl viele Enzyme aus hyperthermophilen Mikroorganismen auch unter hohen Temperaturen stabil sind, gilt dies nicht generell für die zellulären Strukturen thermo- und hyperthermophiler Organismen. Zu der hohen Temperaturstabilität von Zellstrukturen tragen in erheblichem Maß niedermolekulare organische Substanzen (Kompatible Solute, „Hypersolutes") im intrazellulären Milieu bei. Verschiedene neuartige Hypersolutes konnten in den letzten Jahren in hyperthermophilen Mikroorganismen erstmals identifiziert werden. In einigen Fällen konnte der Beitrag dieser Verbindungen zum Schutz zellulärer Strukturen - vor allem Enzymen - gegenüber Hitze- und Trockenheit bereits eindrucksvoll gezeigt werden, bitop hat Technologien zur Produktion kompatibler Solute aus thermophilen Mikroorganismen entwickelt.Hyperthermophiles are very unusual microorganisms because they grow optimally at temperatures (60-110 ° C), which would lead to massive damage to cellular structures in mesophilic ("normal") organisms. In recent years, a large amount of research has therefore been carried out to determine the Identify biochemical components that lead to the remarkable thermal, chemical and physical stabilization of cell structures, with the focus of the research work on the isolation of thermostable enzymes, since numerous enzymatically catalyzed industrial processes take place under extreme environmental conditions and suitable biocatalysts are sought. Although many enzymes from hyperthermophilic microorganisms are stable even at high temperatures, this does not generally apply to the cellular structures of thermo- and hyperthermophilic organisms. Low molecular weight organic substances (compatible solutes, "hypersolutes") in the intracellular milieu make a significant contribution to the high temperature stability of cell structures. Various novel hypersolutes have been identified in hyperthermophilic microorganisms in recent years. In some cases, the contribution of these compounds to Protection of cellular structures - especially enzymes - against heat and drought has already been impressively demonstrated, bitop has developed technologies for the production of compatible solutes from thermophilic microorganisms.
Problemstellungproblem
Die Haut ist als Grenzschicht und Oberfläche des menschlichen Körpers einer Vielzahl externer Stressfaktoren ausgesetzt. Die Human-Haut ist ein Organ, das mit verschiedenartig spezialisierten Zelltypen - den Keratinozyten, Melanozyten, Langerhanszellen, Merkel-Zellen und eingelagerten Sinneszellen - den Körper vor äußeren Einflüssen schützt. Hierbei ist zwischen äußeren physikalischen, chemischen und biologischen Einflüssen auf die menschliche Haut zu unterscheiden. Zu den äußeren physikalischen Einflüssen sind thermische und mechanische Einflüsse sowie die Einwirkung von Strahlung, z.B. UV-, VIS, und IR-Strahlung, zu zählen. Unter den äußeren chemischen Einflüssen sind insbesondere die Einwirkung von Toxinen, Allergenen und Substanzen, die an die Desoxyribonukleinsäure anbinden, zu verstehen. Die äußeren biologischen Einflüsse umfassen die Einwirkung fremder Organismen und deren Stoffwechselprodukte.As the boundary 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 that protects the body from external influences with various types of specialized cell types - the keratinocytes, melanocytes, Langerhans cells, Merkel cells and embedded sensory cells. A distinction must be made between external physical, chemical and biological influences on human skin. The external physical influences include thermal and mechanical influences as well as the effect of radiation, e.g. UV, VIS, and IR radiation, count. External chemical influences are to be understood in particular as the effects of toxins, allergens and substances which bind to the deoxyribonucleic acid. The external biological influences include the effects of foreign organisms and their metabolic products.
Eine übermäßige Sonnenstrahlung führt sowohl zu akuten Hautschäden wie beispielsweise Sonnenbrand als auch zu chronischen Veränderungen wie z.B. Hautalterung oder Hautkrebs. Der Sonnenbrand (Erythema solare) entwickelt sich überwiegend als Folge der UV-B-Bestrahlung. Die UV-A-Strahlung hat dagegen einen vergleichsweise geringen Einfluß auf seine Entstehung. Der Sonnenbrand kann von einer leichten Tönung bis hin zu einer starken Verbrennung mit Blasenbildung auftreten. Da diese Folgen frühestens 4-6 h nach der Bestrahlung auftrete, ist es für Gegenmaßnahmen zu spät. Mehrere Sonnenbrände - ganz besonders in der Kindheit - erhöhen deutlich das Hautkrebsrisiko. Ursachen hierfür sind Schädigungen, insbesondere der Nukleinsäuren von menschlichen Hautzellen und eine fehlerhafte Reparatur der geschädigten Desoxyribonukleinsäure im Zellkern sowie wahrscheinlich die immunsuppressive Wirkung der UV-Strahlung, d.h. die Schwächung der Immunreaktion durch UV-Bestrahlung. Die übermäßige UV-A- und UV-B-Exposition trägt zur Hautalterung bzw. Lichtalterung bei, z.B. in Form von strukturellen Veränderungen des Bindegewebes (aktinische Elastose). Die übermäßige UV-B-Exposition ist die wesentliche Ursache für chronische Hautveränderungen.Excessive solar radiation leads to acute skin damage such as sunburn as well as chronic changes such as skin aging or skin cancer. Sunburn (erythema solare) mainly develops as a result of UV-B radiation. In contrast, UV-A radiation has a comparatively minor influence on its formation. Sunburn can range from a light tint to a severe burn with blistering. Since these episodes no earlier than 4-6 h after the radiation occurs, it is too late for countermeasures. Multiple sunburns - especially in childhood - significantly increase the risk of skin cancer. The causes for this are damage, in particular the nucleic acids of human skin cells and a faulty repair of the damaged deoxyribonucleic acid in the cell nucleus, as well as probably the immunosuppressive effect of UV radiation, ie the weakening of the immune response by UV radiation. Excessive UV-A and UV-B exposure contributes to skin aging or light aging, for example in the form of structural changes in the connective tissue (actinic elastosis). Excessive UV-B exposure is the main cause of chronic skin changes.
Aufgrund eines veränderten Freizeitverhaltens, wie z.B. ausgiebiges Sonnenbaden oder Fernreisen in Ländern mit einer starken Sonneneinstrahlung, sind die Gefahren einer UV-Schädigung der Hautzellen in den letzten Jahren stark angestiegen, was sich wiederum in einer Erhöhung des Hautkrebsrisikos niederschlägt. Zusätzlich ist das Hautkrebsrisiko in jüngerer Zeit durch eine zunehmende UV-Strahlung an der Erdoberfläche, ausgelöst durch die Abnahme der Ozonschicht, und durch eine höhere Lebenserwartung der Menschheit deutlich angestiegen.Due to a change in leisure behavior, e.g. Extensive sunbathing or long-distance travel in countries with strong sunlight, the dangers of UV damage to the skin cells have increased significantly in recent years, which in turn is reflected in an increase in the risk of skin cancer. In addition, the risk of skin cancer has recently increased significantly due to increasing UV radiation on the earth's surface, triggered by the decrease in the ozone layer, and by a longer life expectancy for mankind.
Neben dem weiterhin sehr aktuellen Problem der nachhaltigen Zellschädigung durch UV-Strahlung, was durch die Verwendung herkömmlicher Sonnenschutzmittel bislang nur unzureichend gelöst ist, wird der bisher unterschätzte Einfluß der IR-Strahlung im Bereich der thermischen Schädigung von Hautzellen (thermischer Stress denaturiert Zellproteine und -enzyme) in der Forschung aktuell diskutiert. In der Kosmetikindustrie sind keine Wirkstoffe bekannt, die vor Zellstress durch erhöhte Temperatur schützen.In addition to the still very current problem of sustainable cell damage from UV radiation, which has so far only been insufficiently solved by the use of conventional sunscreens, the underestimated influence of IR radiation in the area of thermal damage to skin cells (thermal stress denatures cell proteins and enzymes ) currently being discussed in research. No active ingredients are known in the cosmetics industry that protect against cell stress caused by elevated temperatures.
Jedes Gewebe besitzt ein antioxidatives Potential (AOP) aus enzymatischen und nicht-enzymatischen Antioxydantien, die bei ungestressten Zellen den Gehalt von Prooxidantien unterhalb eines Grenzwertes halten, der für die gesunde Zelle unschädlich ist. Kommt es zu einer Inaktivierung oder Denaturierung dieser natürlichen Antioxydantien wird die Widerstands- und Regenerationsfähigkeit der Haut signifikant erniedrigt. Es sind bisher nur wenige natürliche Substanzen in der präventiven Kosmetik und Dermatologie bekannt, die die zelleigenen Reparaturmechanismen der Zelle aktiv unterstützen und so „von innen" (in vivo) die Zelle z.B. vor erhöhter UV-Strahlung, IR-Strahlung, Wärme, Radikalen, Kälte, Trockenheit, osmotischem Stress oder chemischem Stress schützen. Es bestand daher die Aufgabe, kosmetische und dermatologische Formulierungen zur Verfügung zu stellen, deren Anwendung die obengenannten Hautprobleme beseitigen oder zumindest mindern und insbesondere zum Schutz und zur Stabilisierung von menschlichen Hautzellen und deren organischer Komponenten geeignet sind.Each tissue has an antioxidative potential (AOP) made up of enzymatic and non-enzymatic antioxidants, which keep the content of prooxidants below a limit value in unstressed cells, which is harmless to the healthy cell. If these natural antioxidants are inactivated or denatured, the skin's resistance and regeneration ability is significantly reduced. So far, only a few natural substances in preventive cosmetics and dermatology are known which actively support the cell's own repair mechanisms and thus “from the inside” (in vivo) of the cell, for example against increased UV radiation, IR radiation, heat, radicals, To protect cold, dryness, osmotic stress or chemical stress, the task was therefore to provide cosmetic and dermatological formulations, the use of which eliminates or at least alleviates the abovementioned skin problems and is particularly suitable for protecting and stabilizing human skin cells and their organic components are.
Somit ist es ein generelles Problem der Kosmetik und Dermatologie, dass keine chemisch eindeutig definierten und unschädlichen Wirkstoffe und Additive natürlichen Ursprungs zur Verfügung stehen, um die oben genannten wichtigen Aufgabenstellungen dieser Anwendungsbereiche zufriedenstellend zu lösen. Die vorliegende Erfindung schlägt eine Lösung dieses Problems vor.It is therefore a general problem in cosmetics and dermatology that no chemically clearly defined and harmless active ingredients and additives of natural origin are available in order to satisfactorily solve the above-mentioned important tasks in these areas of application. The present invention proposes a solution to this problem.
Erfindung / Vorteilhafte Wirkungen der ErfindungInvention / Advantageous Effects of Invention
Extremophile Mikroorganismen (Thermophile und Hyperthermophile) schützen sich vor thermischen Stress durch die Bildung von cyclisches Diphosphoglycerat. In Gegenwart dieser Substanzen ist es diesen mikrobiellen Lebewesen daher möglich unter den herrschendenden Extrembedingungen zu existieren, da cyclisches Diphosphoglycerat den Stoffwechsel und die essentiellen organischen Bestandteile stabilisiert und vor Schädigungen schützt.Extremophilic microorganisms (thermophiles and hyperthermophiles) protect themselves from thermal stress through the formation of cyclic diphosphoglycerate. In the presence of these substances it is therefore possible for these microbial organisms to exist under the prevailing extreme conditions, since cyclic diphosphoglycerate stabilizes the metabolism and the essential organic components and protects against damage.
Überraschenderweise wurde nun insbesondere gefunden, dass cyclisches Diphosphoglycerat die Stabilisierungseffekte auch auf der menschlichen Haut zeigt und somit ein idealer Wirkstoff und Additive für kosmetische und dermatologische Präparate darstellen. Cyclisches Diphosphoglycerat stellt somit einen universal einsetzbares und völlig neuartiges Schutzprinzip in der Kosmetik und Dermatologie dar. Somit wird gemäß der Erfindung das o.g. Problem durch die Verwendung von einer oder mehreren Verbindungen ausgewählt aus den Verbindungen der Formeln la (cyclisches Diphosphoglycerat) in kosmetischen und dermatologischen Formulierungen gelöst. Die Erfindung betrifft die Verwendung von einer oder mehreren Verbindungen ausgewählt aus den Verbindungen der Formel la (cyclisches Diphosphoglycerat),Surprisingly, it has now been found in particular that cyclic diphosphoglycerate also shows the stabilizing effects on human skin and thus represents an ideal active ingredient and additive for cosmetic and dermatological preparations. Cyclic diphosphoglycerate thus represents a universally applicable and completely new protective principle in cosmetics and dermatology. Thus, according to the invention, the above-mentioned problem is selected by using one or more compounds from the compounds of the formulas la (cyclic diphosphoglycerate) in cosmetic and dermatological formulations solved. The invention relates to Use of one or more compounds selected from the compounds of the formula Ia (cyclic diphosphoglycerate),
den physiologisch verträglichen Salzen der Verbindung la , den stereoisomeren Formen der Verbindungen der Formel la sowie von Derivaten zur Herstellung einer kosmetischen oder dermatologischen Formulierung zum Schutz und zur Stabilisierung der menschlichen Hautzellen sowie deren organischer Bestandteile wie z.B. Proteine, Enzyme, Membranen, Nukleinsäuren oder Antioxidantien.the physiologically tolerable salts of the compound la, the stereoisomeric forms of the compounds of the formula la and derivatives for the preparation of a cosmetic or dermatological formulation for protecting and stabilizing human skin cells and their organic constituents, e.g. Proteins, enzymes, membranes, nucleic acids or antioxidants.
Als Salze kommen die Alkali- und Erdalkalisalze, insbesondere aber das Na- und K-Salz in Frage. Als Ester können die Ester physiologisch verträgliche Alkohole eingesetzt werden, insbesondere von Cι-C -Alkoholen, wie Methanol, Ethanol, Propanole oder Butanole.Possible salts are the alkali and alkaline earth salts, but especially the Na and K salts. The esters which can be used are the esters of physiologically acceptable alcohols, in particular C 1 -C 4 alcohols, such as methanol, ethanol, propanols or butanols.
Die Erfindung betrifft insbesondere die Verwendung von einer oder mehreren Verbindungen ausgewählt aus den Verbindungen der Formel la, den physiologisch verträglichen Salzen der Verbindungen der Formel la und den stereoisomeren Formen der Verbindungen der Formel la zur Herstellung einer kosmetischen oder dermatologischen Formulierung zum Schutz und zur Stabilisierung der menschlichen Hautzellen sowie deren organischer Bestandteile wie z.B. Proteine, Enzyme, Membranen, Nukleinsäuren, Antioxidantien usw. vor physikalischen, chemischen und biologischen Einflüssen wie z.B. vor Strahlung (UV, IR, VIS-Strahlung), vor denaturierenden Substanzen, vor Temperatur oder vor Kälte. Die vorliegende Erfindung beschreibt dieses Schutzprinzip erstmals. Die Einsatzmöglichkeiten sind sehr vielseitig und können im Rahmen der Erfindung nur beispielhaft beschrieben werden. Die Erfindung soll durch Nennung von Beispielen jedoch nicht eingeschränkt werden.The invention relates in particular to the use of one or more compounds selected from the compounds of the formula Ia, the physiologically tolerable salts of the compounds of the formula Ia and the stereoisomeric forms of the compounds of the formula Ia for the production of a cosmetic or dermatological formulation for protecting and stabilizing the human skin cells and their organic components such as proteins, enzymes, membranes, nucleic acids, antioxidants etc. from physical, chemical and biological influences such as from radiation (UV, IR, VIS radiation), from denaturing substances, from temperature or from cold. The present invention describes this principle of protection for the first time. The possible uses are very diverse and can only be described by way of example within the scope of the invention. However, the invention is not intended to be limited by giving examples.
Membranen stellen die natürliche Barriere von Zellen und Zellorganellen zum umgebenden Medium dar. Es ist durch die Membranen möglich, in den einzelnen Zellen bzw. Zellbestandteilen ein konstantes inneres Milieu zu gewährleisten. Biologische Membranen sind Mehrkomponentensysteme, die im allgemeinen aus Lipiden, Cholesterol und Proteinen bestehen. Die genaue Zusammensetzung einzelner Membranen unterliegt je nach ihrer Herkunft mehr oder weniger großen Schwankungsbreiten. Elementare Bestandteile von Membranen sind jedoch Lipide und Proteine.Membranes represent the natural barrier of cells and cell organelles to the surrounding medium. The membranes make it possible to ensure a constant internal environment in the individual cells or cell components. Biological membranes are multi-component systems that generally consist of lipids, cholesterol and proteins. The exact composition of individual membranes is subject to varying fluctuations depending on their origin. However, elementary components of membranes are lipids and proteins.
Lipide lassen sich in die sogenannten „einfachen" Lipide wie Fette und Wachse und „komplexen" Lipide unterteilen. Als Grundbausteine von Membranen sind hierbei die komplexen Lipide wie die Glycerophospholipide (Glycerinphosphatide) am weitesten verbreitet. Die allgemeine Struktur dieser Membranbestandteile leitet sich von sn-Glycerin-3-phosphorsäure (folgende Abb.; R1 , R2, R3=H) ab.Lipids can be divided into the so-called "simple" lipids such as fats and waxes and "complex" lipids. Complex lipids such as glycerophospholipids (glycerol phosphatides) are the most common building blocks of membranes. The general structure of these membrane components is derived from sn-glycerol-3-phosphoric acid (following figure; R1, R2, R3 = H).
Es handelt sich dabei um Phosphorsäurediester, in denen der Glycerinrest i.a. mit gesättigten (R1) und ungesättigten (R2) Fettsäuren kondensiert ist. Der Phosphorsäurerest ist zusätzlich mit einer Komponente alkoholischer Struktur wie Inositol oder Ethanolamin (R3) kondensiert.These are phosphoric acid diesters in which the glycerol residue generally is condensed with saturated (R1) and unsaturated (R2) fatty acids. The phosphoric acid residue is additionally condensed with a component of alcoholic structure such as inositol or ethanolamine (R3).
Durch ihre ambivalente Struktur mit einem hydrophilen Phosphatrest und lipophilen Fettsäureresten sind Glycerophospholipide in der Lage, in wäßriger Lösung Aggregate zu bilden (z.B. Doppelschichten oder Miccellen), bei denen der nur hydrophile Phosphatrest mit der wäßrigen Phase in Berührung kommt. Diese Struktur findet man auch in Form geschlossener lamellarer Vesikel, den sogenannten Liposomen wieder.Due to their ambivalent structure with a hydrophilic phosphate residue and lipophilic fatty acid residues, glycerophospholipids are able to in water Solution to form aggregates (eg double layers or micelles) in which the only hydrophilic phosphate residue comes into contact with the aqueous phase. This structure is also found in the form of closed lamellar vesicles, the so-called liposomes.
Ein Beispiel für die Gruppe von Lipiden mit zwei Phospodiestergruppen den sogenannten Diphosphatidylglycerinen (Cardiolipinen) zeigt folgende Abbildung:The following figure shows an example of the group of lipids with two phosphodiester groups, the so-called diphosphatidylglycerols (cardiolipins):
R1R1
Analog zu anderen kompatiblen Soluten aus thermophilen oder hyperthermophilen Mikroorganismen, denen eine Lipid-Grundstruktur zugrunde liegt, lassen sich im Falle des cyclischen 2,3-Diphosphoglycerats strukturelle Vergleiche mit den Diphosphatidylglycerinen herstellen. Innerhalb eines Moleküls sind zwei Phosphatreste mit einem Glycerinrest verknüpft. Im Fall des cDPG geschieht dies durch einen intramolekularen Ringschluß über die Hydroxygruppen in der 2- und 3-Position, während es sich bei den Diphosphatidylglycerinen um offenkettige Verbindungen handelt.Analogous to other compatible solutes from thermophilic or hyperthermophilic microorganisms, which are based on a basic lipid structure, structural comparisons with the diphosphatidylglycerols can be made in the case of the cyclic 2,3-diphosphoglycerate. Within a molecule, two phosphate residues are linked to one glycerol residue. In the case of the cDPG, this is done by an intramolecular ring closure via the hydroxyl groups in the 2- and 3-position, while the diphosphatidylglycerols are open-chain compounds.
Entscheidend für die stabilisierende Wirkung des cDPG ist, dass die Substanz als Kaliumsalz vorliegt. Im Zusammenhang mit der stabilisierenden Wirkung (Thermoadaptor) des cDPG diskutiert manIt is crucial for the stabilizing effect of the cDPG that the substance is present as a potassium salt. One discusses in connection with the stabilizing effect (thermoadaptor) of the cDPG
• Bindung hydrophiler Proteindomainen über OH-Gruppen (Simulation von Wasser), Verhinderung von Wasserstoffbrückenbildung innerhalb der• Binding of hydrophilic protein domains via OH groups (simulation of water), prevention of hydrogen bonding within the
Proteinstruktur und zwischen Proteinen während der Trocknung und Rehydrierung.Protein structure and between proteins during drying and rehydration.
• Präsentation eines Phosphatanions: Stabilisierung von Proteinseitenketten über ionische und van-der-Waals Wechselwirkungen. Desweiteren zeichnet sich DIP durch folgende Merkmale aus:• Presentation of a phosphate anion: stabilization of protein side chains via ionic and van der Waals interactions. Furthermore DIP is characterized by the following features:
- Hohe chemische und physikalische Stabilität- High chemical and physical stability
- pH-Stabilität- pH stability
- Lichtstabilität- light stability
- Sehr gute Löslichkeit in Wasser- Very good solubility in water
- Hohe Biokompatibilität- High biocompatibility
- Natürlicher Schutzstoff aus R1 Mikroorganismen- Natural protective material from R1 microorganisms
- kein zu erwartendes allergenes Potential (Substanz aus Extremophilen)- no expected allergenic potential (substance from extremophiles)
Letztendlich darf die solubilisierende Wirkung von cDPG als Ersatz des Wassers in der Zelle nicht vergessen werden. cDPG ist wie die anderen Kompatiblen Solute das natürliche Lösungsmittel der Zelle. Um ihre Wirkung in der Zelle überhaupt entfalten zu können, müssen biogene Stoffe solubilisiert werden. Bislang liegen keine Daten zur Toxizität der Substanz vor. Die intrazelluläre Konzentration an cDPG innerhalb der Zelle (Methanothermus fervidus) liegt jedoch über 300 mM, so dass auch hier eine hohe Biokompatibilität zu erwarten ist! Temperaturschutz von ProteinenUltimately, the solubilizing effect of cDPG as a substitute for water in the cell should not be forgotten. Like the other Compatible Solutes, cDPG is the cell's natural solvent. In order to be able to develop their effects in the cell, biogenic substances have to be solubilized. No data on the toxicity of the substance are available to date. However, the intracellular concentration of cDPG within the cell (Methanothermus fervidus) is over 300 mM, so that a high level of biocompatibility can also be expected here! Protecting the temperature of proteins
In Experimenten konnte gezeigt werden, daß cDPG sehr gute und zum Teil im Vergleich mit anderen kompatiblen Soluten um Dimensionen bessere Schutzwirkung bei der thermisch bedingten Denaturierung von Enzymen besitzt. Beim Einfrieren von Proteinlösungen (LDH) zeigt cDPG gute Stabilisierungseigenschaften.In experiments it could be shown that cDPG has very good protective properties in the thermally induced denaturation of enzymes, some of which are better in comparison to other compatible solutes. When freezing protein solutions (LDH), cDPG shows good stabilizing properties.
Gewerbliche Anwendung der ErfindungCommercial application of the invention
Die gewerbliche Anwendung der Erfindung liegt im gesamten Bereich der kosmetischen und dermatologischen Produkte sowie als Forschungsreagenzien im Bereich der kosmetischen und dermatologischen Entwicklung. Ebenso liegt eine gewerbliche Anwendung in der postoperativen Behandlung der Haut (z.B. Wundversorgung zur Unterstützung des Heilungsprozesses) und im Zusatz der Verbindungen zur Pflastern, Masken und Verbänden die auf die Haut aufgebracht werden.The commercial application of the invention is in the entire field of cosmetic and dermatological products and as research reagents in the field of cosmetic and dermatological development. There is also a commercial application in the postoperative treatment of the skin (e.g. wound care to support the healing process) and in the addition of the connections to the plasters, masks and bandages that are applied to the skin.
Mögliche weitere Anwendungen der Verbindung la in der Kosmetik und Dermatologie sind z.B.:Possible further applications of the compound la in cosmetics and dermatology are, for example:
Mikroeinkapselung kosmetischer Wirkstoffe und AdditiveMicroencapsulation of cosmetic ingredients and additives
- Liposomenstabilisierung- Liposome stabilization
- Feuchtigkeitsspender- moisturizer
- Radikal- und UV-Schutz- Radical and UV protection
- Schutz vor Umweltgiften und Salzen- Protection against environmental toxins and salts
- Osmostressprotektantien Weg zur Ausführung der Erfindung inkl. Beispiele- Osmostress protectants Way of carrying out the invention including examples
Die Herstellung der kosmetischen und dermatologischen Formulierungen erfolgt, indem eine oder mehrere Verbindungen der Formel la (cyclisches Diphosphoglycerat), den physiologisch verträglichen Salzen der Verbindungen der Formel la, den stereoisomeren Formen der Verbindung der Formel la oder Derivate gegebenenfalls mit Hilfs- und/oder Trägerstoffen in eine geeignete Formulierungsform gebracht werden.The cosmetic and dermatological formulations are prepared by one or more compounds of the formula la (cyclic diphosphoglycerate), the physiologically tolerable salts of the compounds of the formula la, the stereoisomeric forms of the compound of the formula la or derivatives, optionally with auxiliaries and / or carriers be brought into a suitable formulation.
Die Hilfs- und Trägerstoffe stammen aus der Gruppe der Trägermittel, Konservierungsstoffe und anderer üblicher Hilfsstoffe. Die in kosmetischen und dermatologischen Formulierungen enthaltenden Verbindungen der Formel la (cyclisches Diphosphoglycerat), den physiologisch verträglichen Salzen der Verbindungen der Formel la und den stereoisomeren Formen der Verbindungen der Formel la werden äußerlich angewendet. Als Anwendungsform seien z.B. genannt: Lösungen, Suspensionen, Emulsionen, Pasten, Salben, Gele, Cremes, Lotionen, Puder, Seifen, tensidhaltige Reinigungspräparate, Öle und Sprays. Zusätzlich können den Formulierungen beliebige übliche Trägerstoffe, Hilfsstoffe und gegebenenfalls weitere Wirkstoffe zugesetzt werden. Vorzuziehende Hilfsstoffe stammen aus der Gruppe der Konservierungsstoffe, Antioxidantien, Stabilisatoren, Lösungsvermittler, Vitamine, Färbemittel und Geruchsverbesserer.The auxiliaries and carriers come from the group of carriers, preservatives and other customary auxiliaries. The compounds of the formula la (cyclic diphosphoglycerate) contained in cosmetic and dermatological formulations, the physiologically tolerable salts of the compounds of the formula la and the stereoisomeric forms of the compounds of the formula la are used externally. As an application form e.g. called: solutions, suspensions, emulsions, pastes, ointments, gels, creams, lotions, powders, soaps, surfactant-containing cleaning preparations, oils and sprays. In addition, any customary excipients, auxiliaries and, if appropriate, further active ingredients can be added to the formulations. Preferred additives come from the group of preservatives, antioxidants, stabilizers, solubilizers, vitamins, colorants and odor improvers.
Salben, Pasten, Cremes und Gele können neben einer oder mehrere Verbindungen ausgewählt aus den Verbindungen der Formel la die üblichen Trägerstoffe enthalten, z.B. tierische und pflanzliche Fette, Wachse, Paraffine, Stärke, Traganth, Cellulosederivate, Polyethylenglykole, Silicone, Bentonite, Kieselsäure, Talkum und Zinkoxid oder Gemische dieser Stoffe.In addition to one or more compounds selected from the compounds of the formula Ia, ointments, pastes, creams and gels can contain the usual 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 these substances.
Puder und Sprays können neben einer oder mehrere Verbindungen ausgewählt aus den Verbindungen der Formel la zusätzlich zu den üblichen Trägerstoffen die üblichen Treibmittel, z.B. Chlorfluorkohlenwasserstoffe, Propan/Butan oder Dimethylether, enthalten. Lösungen und Emulsionen können neben einer oder mehrere Verbindungen ausgewählt aus den Verbindungen der Formel la zusätzlich die üblichen Trägerstoffen wie Lösungsmittel, Lösungsvermittler und Emulgatoren oder Öle enthalten.In addition to one or more compounds selected from the compounds of the formula Ia, powders and sprays can contain the usual blowing agents, for example chlorofluorocarbons, propane / butane or dimethyl ether, in addition to the customary carriers. In addition to one or more compounds selected from the compounds of the formula Ia, solutions and emulsions can additionally contain the customary carriers, such as solvents, solubilizers and emulsifiers or oils.
Suspensionen können neben einer oder mehrere Verbindungen ausgewählt aus den Verbindungen der Formel la zusätzliche Trägerstoffe wie z.B. Wasser oder Ethanol enthalten.In addition to one or more compounds selected from the compounds of the formula Ia, suspensions can contain additional carriers such as e.g. Contain water or ethanol.
Weitere Applikationsformen sind z.B. Seifen, Tensidhaltige Reinigungsmittel, Gesichts- und Körperöle, Lippenstifte, Lippenpflegestifte, Mascara, Eyeliner, Lidschatten, Rouge, Puder-, Emulsions- und Wachs-Make up sowie Sonnenschutz-, Prä-Sun- und After-Sun-Präparate.Other forms of application are e.g. Soaps, detergents containing surfactants, facial and body oils, lipsticks, lip care sticks, mascara, eyeliner, eyeshadow, blush, powder, emulsion and wax make-up as well as sunscreen, pre-sun and after-sun preparations.
Der Anteil der Verbindung der Formel la (cyclisches Diphosphoglycerat), den physiologisch verträglichen Salzen der Verbindungen la, und den stereoisomeren Formen der Verbindungen der Formel la kosmetischen und dermatologischen Formulierungen beträgt vorzugsweise 0,0001 bis 50 Gew. %, besonders bevorzugt von 0,001 bis 10 Gew. % bezogen auf die gesamte kosmetische Formulierung.The proportion of the compound of the formula Ia (cyclic diphosphoglycerate), the physiologically tolerable salts of the compounds IA, and the stereoisomeric forms of the compounds of the formula IA cosmetic and dermatological formulations is preferably from 0.0001 to 50% by weight, particularly preferably from 0.001 to 10 % By weight based on the entire cosmetic formulation.
Die Applikation von cyclisches Diphosphoglycerat unterstützt z.B. durch die nachgewiesene Stabilisierung gegen thermische Proteindenaturierung und - inaktivierung das zelleigene antioxidative Potential. Somit wird einer Schädigung durch Radikale entgegengewirkt. Durch den nachgewiesenen DNA-Schutz kompatibler Solute und deren proteinstabilisierende Wirkung stellt der erfindungsgemäße Einsatz von cyclisches Diphosphoglycerat eine neue Art des aktiven Sonnenschutzes (z.B. UV- und IR-Strahlung) in der Kosmetik und Dermatologie dar.The application of cyclic diphosphoglycerate supports e.g. through the proven stabilization against thermal protein denaturation and inactivation the cell's own antioxidative potential. Damage caused by radicals is thus counteracted. Due to the proven DNA protection of compatible solutes and their protein-stabilizing effect, the use of cyclic diphosphoglycerate according to the invention represents a new type of active sun protection (e.g. UV and IR radiation) in cosmetics and dermatology.
Die nachfolgenden Beispiele sollen die vorliegende Erfindung verdeutlichen, ohne sie einzuschränken. Beispiel O/W-LotionThe following examples are intended to illustrate the present invention without restricting it. Example O / W lotion
Aus folgenden Komponenten wird eine erfindungsgemäße Lotion (O/W) enthaltend cyclisches Diphosphoglycerat hergestellt:A lotion (O / W) according to the invention containing cyclic diphosphoglycerate is produced from the following components:
Als Konservierungsmittel können 0,05% Propyl-hydroxybenzoat oder 0,15% Methyl-4-hydroxybenzoat verwendet werden. Beispiel O/W-Creme0.05% propyl hydroxybenzoate or 0.15% methyl 4-hydroxybenzoate can be used as a preservative. Example O / W cream
Aus folgenden Komponenten wird eine erfindungsgemäße Creme (O/W) enthaltend cyclisches Diphosphoglycerat hergestellt:A cream (O / W) according to the invention containing cyclic diphosphoglycerate is produced from the following components:
Als Konservierungsmittel können 0,05% Propyl-hydroxybenzoat oder 0,15% Methyl-4-hydroxybenzoat verwendet werden. 0.05% propyl hydroxybenzoate or 0.15% methyl 4-hydroxybenzoate can be used as a preservative.
Beispiel Liposomenhaltiges GelExample of a liposome-containing gel
Aus folgenden Komponenten wird ein erfindungsgemäßes liposomenhaltiges Gel enthaltend cyclisches Diphosphoglycerat hergestellt:An inventive liposome-containing gel containing cyclic diphosphoglycerate is produced from the following components:
Als Konservierungsmittel können 0,05% Propyl-hydroxybenzoat oder 0,15% Methyl-4-hydroxybenzoat verwendet werden. Beispiel Gel0.05% propyl hydroxybenzoate or 0.15% methyl 4-hydroxybenzoate can be used as a preservative. Example gel
Aus folgenden Komponenten wird ein erfindungsgemäßes Gel (O/W) enthaltend cyclisches Diphosphoglycerat hergestellt:An inventive gel (O / W) containing cyclic diphosphoglycerate is produced from the following components:
Als Konservierungsmittel können 0,05% Propyl-hydroxybenzoat oder 0,15% Methyl-4-hydroxybenzoat verwendet werden. 0.05% propyl hydroxybenzoate or 0.15% methyl 4-hydroxybenzoate can be used as a preservative.
Beispiel SonnenschutzemulsionExample sun protection emulsion
Aus folgenden Komponenten wird eine erfindungsgemäße Sonnenschutzemulsion enthaltend cyclisches Diphosphoglycerat hergestellt:A sunscreen emulsion according to the invention containing cyclic diphosphoglycerate is produced from the following components:
Als Konservierungsmittel können 0,05% Propyl-hydroxybenzoat oder 0,15% Methyi-4-hydroxybenzoat verwendet werden. Beispiel Sonnenlotion0.05% propyl hydroxybenzoate or 0.15% methyl 4-hydroxybenzoate can be used as a preservative. Example sun lotion
Aus folgenden Komponenten wird eine erfindungsgemäße emulgatorfreie Sonnenlotion SPF 30 (W/O) enthaltend cyclisches Diphosphoglycerat hergestellt:An emulsifier-free sun lotion SPF 30 (W / O) containing cyclic diphosphoglycerate is produced from the following components:
Als Konservierungsmittel können 0,05% Propyl-hydroxybenzoat oder 0,15% Methyl-4-hydroxybenzoat verwendet werden. Beispiel Haarwasser0.05% propyl hydroxybenzoate or 0.15% methyl 4-hydroxybenzoate can be used as a preservative. Example hair tonic
Aus folgenden Komponenten wird ein erfindungsgemäßes Haarwasser enthaltend cyclisches Diphosphoglycerat hergestellt:A hair tonic according to the invention containing cyclic diphosphoglycerate is produced from the following components:
Als Konservierungsmittel können 0,05% Propyl-hydroxybenzoat oder 0,15% Methyl-4-hydroxybenzoat verwendet werden. 0.05% propyl hydroxybenzoate or 0.15% methyl 4-hydroxybenzoate can be used as a preservative.
Beispiel SprayformulierungExample spray formulation
Aus folgenden Komponenten wird eine erfindungsgemäße Sprayformulierung enthaltend cyclisches Diphosphoglycerat hergestellt:A spray formulation according to the invention containing cyclic diphosphoglycerate is produced from the following components:
Als Konservierungsmittel können 0,05% Propyl-hydroxybenzoat oder 0,15% Methyl-4-hydroxybenzoat verwendet werden. 0.05% propyl hydroxybenzoate or 0.15% methyl 4-hydroxybenzoate can be used as a preservative.

Claims

Patentansprüche claims
1. Kosmetische(s) oder dermatologische(s) topische(s) Formulierung,1. Cosmetic or dermatological (s) topical formulation,
Zubereitung oder Produkt enthaltend eine der Verbindungen der Formel la, den physiologisch verträglichen Salzen der Verbindungen der Formel la, den stereoisomeren Formen der Verbindungen der Formel la und den Derivaten derPreparation or product containing one of the compounds of formula la, the physiologically tolerable salts of the compounds of formula la, the stereoisomeric forms of the compounds of formula la and the derivatives of
Verbindungen der Formel la.Compounds of the formula la.
2. Formulierung nach Anspruch 1 , dadurch gekennzeichnet, dass die Verbindungen der Formel la, den physiologisch verträglichen Salzen der Verbindungen der Formel la, den stereoisomeren Formen der Verbindungen der Formel la und den Derivaten der Verbindungen der Formel la in Konzentrationen von 0,01 - 50 Gew.-%, bevorzugt 0,05 - 10 Gew.-%, insbesondere 0,1 -5 Gew-% bezogen auf das Gesamtgewicht der Formulierung, Zubereitung oder dem Produkt vorliegen.2. Formulation according to claim 1, characterized in that the compounds of formula la, the physiologically acceptable salts of the compounds of formula la, the stereoisomeric forms of the compounds of formula la and the derivatives of the compounds of formula la in concentrations of 0.01 - 50% by weight, preferably 0.05-10% by weight, in particular 0.1 -5% by weight, based on the total weight of the formulation, preparation or the product are present.
3. Formulierungen nach Anspruch 1 oder 2, zum Schutz und zur Stabilisierung von menschlichen Hautzellen. 3. Formulations according to claim 1 or 2, for the protection and stabilization of human skin cells.
4. Formulierung nach Anspruch 1 oder 2, dadurch gekennzeichnet, dass die Nukleinsäuren von menschlichen Hautzellen vor physikalischen, chemischen und biologischen Einflüssen geschützt und stabilisiert werden.4. Formulation according to claim 1 or 2, characterized in that the nucleic acids of human skin cells are protected and stabilized against physical, chemical and biological influences.
5. Formulierung nach Anspruch 1 oder 2, dadurch gekennzeichnet, dass die Nukleinsäuren von menschlichen Hautzellen vor UV-Strahlung und IR- Strahlung geschützt werden.5. Formulation according to claim 1 or 2, characterized in that the nucleic acids of human skin cells are protected from UV radiation and IR radiation.
6. Formulierung nach Anspruch 1 oder 2, dadurch gekennzeichnet, dass Nukleinsäuren von menschlichen Hautzellen vor denaturierenden Substanzen geschützt und stabilisiert werden.6. Formulation according to claim 1 or 2, characterized in that nucleic acids of human skin cells are protected and stabilized against denaturing substances.
7. Formulierung nach Anspruch 1 oder 2, dadurch gekennzeichnet, dass Nukleinsäuren von menschlichen Hautzellen vor Enzymen geschützt und/oder stabilisiert werden.7. Formulation according to claim 1 or 2, characterized in that nucleic acids of human skin cells are protected from enzymes and / or stabilized.
8. Formulierung nach Anspruch 1 oder 2, dadurch gekennzeichnet, dass menschliche Hautzellen vor Viren, Viroiden und Prionen geschützt und stabilisiert werden.8. Formulation according to claim 1 or 2, characterized in that human skin cells are protected and stabilized against viruses, viroids and prions.
9. Formulierung nach Anspruch 1 oder 2, dadurch gekennzeichnet, dass menschliche Hautzellen vor Iow-infective agents geschützt und stabilisiert werden.9. Formulation according to claim 1 or 2, characterized in that human skin cells are protected and stabilized from Iow-infective agents.
10. Formulierung nach Anspruch 1 oder 2 zur Pflege und/oder Prophylaxe einer trockenen und/oder schuppigen Haut.10. Formulation according to claim 1 or 2 for the care and / or prophylaxis of dry and / or flaky skin.
11. Formulierung nach Anspruch 1 oder 2 zum Schutz der menschlichen Haut gegen Trockenheit und/oder erhöht Salzkonzentrationen (größer 1 % w/w).11. Formulation according to claim 1 or 2 for protecting human skin against dryness and / or increased salt concentrations (greater than 1% w / w).
12. Formulierung nach Anspruch 1 oder 2 zum Schutz von Zellen, Proteinen, Proteinkomplexen, Lipoproteinen, Ribosomen und/oder12. Formulation according to claim 1 or 2 for the protection of cells, proteins, protein complexes, lipoproteins, ribosomes and / or
Biomembranen der menschlichen Haut. Biomembranes of human skin.
13. Formulierung nach Anspruch 1 oder 2 zum Schutz der Mikroflora der menschlichen Haut.13. Formulation according to claim 1 or 2 for protecting the microflora of human skin.
14. Formulierung nach Anspruch 1 oder 2 zur Stabilisierung der natürlichen Hautbarriere.14. Formulation according to claim 1 or 2 for stabilizing the natural skin barrier.
15. Formulierung nach Anspruch 1 oder 2 als wasserretendierende15. Formulation according to claim 1 or 2 as water-retaining
(wasserbindende) Substanz.(water-binding) substance.
16. Formulierung nach Anspruch 1 oder 2 als Radikalfänger und/oder Antioxidants sowie ihre Verwendung zur Behandlung und/oder Prophylaxe der durch oxidative Beanspruchung hervorgerufenen Hautalterung und von entzündlichen Reaktionen.16. Formulation according to claim 1 or 2 as a radical scavenger and / or antioxidant and its use for the treatment and / or prophylaxis of skin aging caused by oxidative stress and of inflammatory reactions.
17. Formulierung nach Anspruch 1 oder 2 zur Steigerung und Beschleunigung der Immunantwort der menschlichen Hautzellen beim Schutz von Zellen, Proteinen und/oder Biomembranen der menschlichen Haut bei physikalischen, chemischen und biologischen Stresseinflüssen.17. Formulation according to claim 1 or 2 for increasing and accelerating the immune response of human skin cells in the protection of cells, proteins and / or biomembranes of human skin under physical, chemical and biological stress influences.
18. Formulierung nach Anspruch 1 oder 2, dadurch gekennzeichnet, dass die kosmetische oder dermatologische Formulierung einen oder mehrere UV-Filter enthält.18. Formulation according to claim 1 or 2, characterized in that the cosmetic or dermatological formulation contains one or more UV filters.
19. Formulierung nach Anspruch 1 oder 2, dadurch gekennzeichnet, dass die kosmetische oder dermatologische Formulierung eine oder mehrere Substanzen ausgewählt aus Enzymen, Vitaminen und Vitamin-Derivaten enthält.19. Formulation according to claim 1 or 2, characterized in that the cosmetic or dermatological formulation contains one or more substances selected from enzymes, vitamins and vitamin derivatives.
20. Formulierung nach Anspruch 1 oder 2, dadurch gekennzeichnet, dass die Nukleinsäuren der Zellen der Epidermis geschützt und stabilisiert werden.20. Formulation according to claim 1 or 2, characterized in that the nucleic acids of the cells of the epidermis are protected and stabilized.
21. Verwendung einer Verbindung der Formel la, den physiologisch verträglichen Salzen der Verbindung der Formel la, den stereoisomeren Formen der Verbindung der Formel la und den Derivaten der Verbindungen der Formel la, gegebenenfalls zusammen mit einem oder mehreren weiteren Wirkstoffen und Additiven, in einer Formulierung zur äußeren Anwendung in Form einer Lösung, einer Suspension, einer Emulsion, einer Paste, einer Salbe, eines Gels, einer Creme, einer Lotion, eines Puders, einer Seife, eines tensidhaltigen Reinigungspräparats, eines Öls, eines Lippenstifts, eines Lippenpflegestifts, einer Mascara, eines Eyeliners, von Lidschatten, von Rouge, eines Puder-, Emulsions- oder Wachs-Make ups, eines Sonnenschutz-, Prä-Sun und After- Sun-Präparats, eines Haarwassers, eines Pflasters, eines Verbands oder eines Sprays.21. Use of a compound of formula la, the physiologically tolerable salts of the compound of formula la, the stereoisomeric forms the compound of the formula Ia and the derivatives of the compounds of the formula Ia, optionally together with one or more further active ingredients and additives, in a formulation for external use 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 cleaning preparation, an oil, a lipstick, a lip balm, a mascara, an eyeliner, eyeshadow, blush, a powder, emulsion or wax make-up, a sunscreen, pre-sun and after-sun preparation, a hair tonic, a plaster, a bandage or a spray.
22. Kosmetische Formulierung, enthaltend eine oder mehrere Verbindungen ausgewählt aus den Verbindungen der Formel la, den physiologisch verträglichen Salzen der Verbindungen der Formel la, den stereoisomeren Formen der Verbindungen der Formel la und den Derivaten der Verbindungen.22. Cosmetic formulation comprising one or more compounds selected from the compounds of the formula la, the physiologically tolerable salts of the compounds of the formula la, the stereoisomeric forms of the compounds of the formula la and the derivatives of the compounds.
23. Dermatologische Formulierung enthaltend eine oder mehrere Verbindungen ausgewählt aus den Verbindungen der Formel la, den physiologisch verträglichen Salzen der Verbindungen der Formel la, den stereoisomeren Formen der Verbindungen der Formel la und den Derivaten der Verbindungen.23. Dermatological formulation containing one or more compounds selected from the compounds of the formula Ia, the physiologically tolerable salts of the compounds of the formula Ia, the stereoisomeric forms of the compounds of the formula Ia and the derivatives of the compounds.
24. Kosmetische Formulierung nach Anspruch 22, dadurch gekennzeichnet, dass sie in Form einer Lösung, einer Suspension, einer Emulsion, einer Paste, einer Salbe, eines Gels, einer Creme, einer Lotion, eines Puders, einer Seife, eines tensidhaltigen Reinigungspräparats, eines Öls, eines Lippenstifts, eines Lippenpflegestifts, einer Mascara, eines Eyeliners, von Lidschatten, von Rouge, eines Puder-, Emulsions- oder Wachs-Make ups, eines Sonnenschutz-, Prä-Sun und After-Sun-Präparats, eines Haarwassers, eines Pflasters, eines Verbands oder eines Sprays vorliegt.24. Cosmetic formulation according to claim 22, 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 cleaning preparation, one Oil, a lipstick, a lipstick, a mascara, an eyeliner, eyeshadow, blush, a powder, emulsion or wax make-up, a sunscreen, pre-sun and after-sun preparation, a hair tonic, one Patch, bandage or spray.
25. Dermatologische Formulierung nach Anspruch 23, dadurch gekennzeichnet, dass sie in Form einer Lösung, einer Suspension, einer25. Dermatological formulation according to claim 23, characterized in that it is in the form of a solution, a suspension, a
Emulsion, einer Paste, einer Salbe, eines Gels, einer Creme, einer Lotion, eines Puders, einer Seife, eines tensidhaltigen Reinigungspräparats, eines Öls, eines Lippenstifts, eines Lippenpflegestifts, einer Mascara, eines Eyeliners, von Lidschatten, von Rouge, eines Puder-, Emulsions- oder Wachs-Make ups, eines Sonnenschutz-, Prä-Sun- und After-Sun-Präparats, eines Haarwassers, eines Pflasters, eines Verbands oder eines Sprays vorliegt. Emulsion, a paste, an ointment, a gel, a cream, a lotion, one Powder, a soap, a surfactant-containing cleaning preparation, an oil, a lipstick, a lip care stick, a mascara, an eyeliner, eyeshadow, blush, a powder, emulsion or wax make-up, a sunscreen, pre-sun and after-sun preparation, a hair tonic, a plaster, a bandage or a spray.
EP01976086A 2000-08-18 2001-08-16 Use of cyclic 2,4-diphosphoglycerates (cdgp) and/or derivatives thereof in cosmetic and dermatological formulations Withdrawn EP1311237A2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE10040931 2000-08-18
DE10040931A DE10040931A1 (en) 2000-08-18 2000-08-18 Use of cyclic 2,4-diphosphoglycerate (cDGP) and / or derivatives in cosmetic and dermatological formulations
PCT/EP2001/009443 WO2002015866A2 (en) 2000-08-18 2001-08-16 Use of cyclic 2,4-diphosphoglycerates (cdgp) and/or derivatives thereof in cosmetic and dermatological formulations

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EP1311237A2 true EP1311237A2 (en) 2003-05-21

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DE10330243A1 (en) * 2003-07-03 2005-01-20 bitop Aktiengesellschaft für biotechnische Optimierung Use of osmolytes derived from extremophilic bacteria for the manufacture of medicines for the external treatment of atopic dermatitis
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
DE102005056538A1 (en) * 2005-11-28 2007-05-31 Merz Pharma Gmbh & Co. Kgaa Composition, useful for e.g. preparing an agent for preventive, dermatological, therapeutic regenerative treatment of skin, comprises unmodified lipids, transferable proteins, non-transferable active substances and additives
JP6094826B2 (en) * 2014-07-16 2017-03-15 トヨタ自動車株式会社 Non-aqueous electrolyte secondary battery, manufacturing method thereof, and non-aqueous electrolyte

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US6296857B1 (en) * 1998-09-23 2001-10-02 Beiersdorf Aktiengesellschaft Cosmetic or dermatological preparations comprising oligopeptides for lightening the skin of age marks and/or for preventing tanning of the skin, in particular tanning of the skin caused by UV radiation
ATE247981T1 (en) * 1999-06-12 2003-09-15 Bitop Ag PHARMACEUTICAL PREPARATION CONTAINING PROTEIN
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WO2002015866A3 (en) 2002-06-06
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US20040097543A1 (en) 2004-05-20
WO2002015866A2 (en) 2002-02-28

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