WO2024083930A1 - Préparation appliquée par voie topique pour améliorer l'état de la peau - Google Patents

Préparation appliquée par voie topique pour améliorer l'état de la peau Download PDF

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WO2024083930A1
WO2024083930A1 PCT/EP2023/079024 EP2023079024W WO2024083930A1 WO 2024083930 A1 WO2024083930 A1 WO 2024083930A1 EP 2023079024 W EP2023079024 W EP 2023079024W WO 2024083930 A1 WO2024083930 A1 WO 2024083930A1
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skin
methylethyl
pyrenylmethyl
substances
preparation
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PCT/EP2023/079024
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German (de)
English (en)
Inventor
Andrea Heuer
Jennifer HÜPEDEN
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Beiersdorf Ag
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Priority claimed from DE102022210999.6A external-priority patent/DE102022210999A1/de
Application filed by Beiersdorf Ag filed Critical Beiersdorf Ag
Publication of WO2024083930A1 publication Critical patent/WO2024083930A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • 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
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73—Polysaccharides
    • A61K8/732—Starch; Amylose; Amylopectin; 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
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73—Polysaccharides
    • A61K8/735—Mucopolysaccharides, e.g. hyaluronic acid; 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
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9789—Magnoliopsida [dicotyledons]
    • 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
    • A61P17/04—Antipruritics
    • 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
    • A61P17/10—Anti-acne agents
    • 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
    • A61Q17/005—Antimicrobial preparations
    • 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

Definitions

  • the present invention relates to topically applicable, in particular cosmetic or dermatological preparations, comprising a substance combination of antimicrobial peptides (AMP), in particular cyclic peptide compounds based on the synthesis of thiazolidine and oxazolidine building blocks, and skin-soothing substances, such as menthoxylpropanediol, substances that strengthen the skin barrier, such as omega-6 fatty acids, and/or flavonoids, such as licochalcones.
  • AMP antimicrobial peptides
  • cyclic peptide compounds based on the synthesis of thiazolidine and oxazolidine building blocks
  • skin-soothing substances such as menthoxylpropanediol
  • substances that strengthen the skin barrier such as omega-6 fatty acids, and/or flavonoids, such as licochalcones.
  • sebum sebum
  • Propionibacterium acnes P. acnes, Cutibacterium acnes, C. acnes
  • Pityrosporum species P. acnes, Cutibacterium acnes, C. acnes
  • the microorganisms break down the sebum into glycerine and fatty acids, which stimulates the sebaceous glands to produce more and attacks and destroys the follicle walls in the skin.
  • a disadvantage of the known acne preparations is that in order to act against Propionibacterium acnes (P. acnes), the proportion of antimicrobial active ingredients is often so high that the preparations are irritating to the skin.
  • Atopic dermatitis (often referred to as eczema) is a chronic inflammatory skin disease with a complex pathogenesis involving genetic susceptibility, immunological and epidermal barrier dysfunction, and environmental factors. Treatment is often by applying moisturizer, avoiding allergens and irritants, and often with topical corticosteroids or immunomodulators.
  • skin care In addition to the treatment of skin diseases such as atopic dermatitis, skin care is an essential prophylactic approach.
  • Improving the condition of human skin in particular providing a preparation suitable for the treatment of atopic dermatitis and/or acne and caring for skin damaged by atopic dermatitis or acne, is therefore one of the essential tasks.
  • AMPs antimicrobial peptides
  • Their effectiveness extends particularly to Gram-negative and Gram-positive bacteria, viruses and fungi.
  • the effect against bacteria is bactericidal, not bacteriostatic.
  • WO 2022106667 A1 describes new cyclic peptide compounds based on the synthesis of thiazolidine and oxazolidine building blocks. These cyclic compounds are suitable for use in cosmetic preparations because they have antimicrobial, antiviral, antibacterial and/or antimycotic activity.
  • Flavonoids are natural substances and belong to the group of polyphenols. They are formally derived from the basic substance flavan (2-phenylchroman). There are around 8,000 compounds in nature.
  • Flavonoids are universally present in plants as secondary plant substances, and thus also in human food. They are said to have particularly antioxidant properties, which is why they are used in cosmetic products, both as plant extracts (e.g. Glycyrrhiza inflata) and as pure substances, for example Licochalcone A.
  • EP 1839645 A1 describes Licochalcone A in cosmetic preparations.
  • the invention is a topically applicable preparation comprising one or more antimicrobial peptides (AMP) and one or more substances selected from the group of skin-soothing substances, skin barrier-strengthening substances and/or flavonoids.
  • the topically applicable preparation thus comprises a substance combination of one or more antimicrobial peptides and, in addition, one or more substances selected from the group of skin-soothing substances, skin barrier-strengthening substances and/or flavonoids.
  • skin-soothing substances, skin barrier-strengthening substances and/or flavonoids are also referred to as “combination partners”, “combination substances” or “combination partner substances”.
  • cyclic peptide compounds based on the synthesis of thiazolidine and oxazolidine building blocks are selected as antimicrobial peptides.
  • the term “peptide compounds based on the synthesis of thiazolidine and oxazolidine building blocks” refers in particular to those peptide compounds which contain at least one thiazolidine or oxazolidine building block. It is therefore particularly preferred that the preparation according to the invention contains one or more antimicrobial peptides which are a cyclic peptide compound of the formula (I): where:
  • Benzothienylmethyl (with the formula -Naphtylmethyl (with the formula -Anthracenylmethyl (with the formula ) and pyrenylmethyl (ie 1-Pyrenylmethyl with the formula -Pyrenylmethyl with the Etc.);
  • - Z is O or S
  • R and R' are each selected from the group consisting of H, methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 2-methylpropyl (isobutyl), 1-methylpropyl (butan-2-yl or sec-butyl), benzyl and propargyl, with the proviso that when R is H, R' is not H;
  • the methyl radical has the formula CH3- and is also abbreviated as "Me”.
  • the ethyl radical with the formula CH3-CH2-, is also abbreviated as "Et”.
  • the n-propyl radical has the formula CH3-CH2-CH2-.
  • the 1-methylethyl radical in the sense of the present invention is also known to the person skilled in the art as isopropyl and has the formula (CHs ⁇ CH-.
  • the n-butyl radical has the formula CH3-CH2-CH2-CH2-.
  • the 2-methylpropyl radical in the sense of the present invention is also known to the person skilled in the art as isobutyl and has the formula (CH3)2CH-CH2-.
  • the 1-methylpropyl radical is also known to the person skilled in the art as butan-2-yl or sec-butyl and has the formula CH3-CH2-CH(CH3)-.
  • the 1,1-dimethylethyl radical in the sense of the present invention is also known to the person skilled in the art as tert-butyl and has the formula (CHsjsCH-.
  • the n-pentyl radical has the formula CH3-CH2-CH2-CH2-CH2-.
  • the 3-methylbutyl radical is also known to the person skilled in the art as isopentyl and has the formula (CH3)2CH-CH2-CH2-.
  • the benzyl (or (I-phenyl)methyl) radical in the sense of the present invention is also abbreviated to "Bn” and has the formula phenyl-CH2-.
  • the propargyl radical is also known to the person skilled in the art as ethynylmethyl or 2-propynyl and has the formula HCHC-CH2-.
  • the formula The radical 3-benzothienylmethyl in the sense of the present invention, has the formula
  • the residue 1-naphthylmethyl in the sense of the present invention has the formula
  • the residue 9-anthracenylmethyl has the formula on.
  • the radical pyrenylmethyl (or pyrenylmethyl), as used herein, stands for a pyrene ring which is connected via one of its outer ring carbon atoms C1 to C10 to a methyl radical, which in turn serves as a connection point for the entire pyrenylmethyl radical, i.e. 1-pyrenylmethyl, 2-pyrenylmethyl, 3-pyrenylmethyl, 4-pyrenylmethyl, 5-pyrenylmethyl, etc. (or 1-pyren-ylmethyl, 2-pyren-ylmethyl, 3-pyren-ylmethyl, 4-pyren- ylmethyl, 5-pyren-ylmethyl, etc.).
  • the residue 2-pyrenylmethyl (or (2-pyrenyl)methyl, pyren-2-ylmethyl, or (pyren-2- yl)methyl), for example, has the formula on, etc.
  • the cyclic compounds according to the invention covered by formula (I) are composed of five amino acid derivatives and a thiazolidine or oxazolidine building block.
  • An "amino acid derivative” in the sense of the present invention is basically understood to mean the classic 20 natural L- and D-a-amino acids and their diastereomers, but also modified derivatives thereof with different radicals (R).
  • the cyclic compound of formula (I) according to the invention only comprises amino acid derivatives with radicals (R) which correspond to the radicals defined for the substituents Yi to Ys.
  • a thiazolidine or oxazolidine building block in the sense of the present invention comprises a 1,3-thiazolidine ring or a 1,3-oxazolidine ring which is connected in position 2 to a carbon atom (C atom), which in turn is connected to the substituent X (and also to an amino group).
  • C atom carbon atom
  • the positions in the thiazolidine or oxazolidine ring result from the standard nomenclature as known to the person skilled in the art, ie: where Z is S or O and the numbers 1-5 define the positions in the ring.
  • the 1,3-thiazolidine ring or 1,3-oxazolidine ring of the thiazolidine or oxazolidine building block is linked to a carboxyl group in position 4 in the free state (i.e. not integrated into a peptide derivative) and is linked to the peptide derivative backbone via an amide group (i.e. in the C-terminus of the thiazolidine or oxazolidine building block) in the linear peptide derivative (i.e. in the linear precursor before cyclization to the cyclic compound according to the invention) or in the cyclic peptide derivative (i.e.
  • directly successive amino acid derivatives each have an alternating absolute and also relative stereochemical configuration of the a-carbon (Ca).
  • (alternating) absolute stereochemical configuration” and “(alternating) relative stereochemical configuration” are known to the person skilled in the art.
  • absolute stereochemical configuration refers to the R/S nomenclature (but not to the relative D/L nomenclature).
  • An "alternating absolute stereochemical configuration" in the sense of the present invention thus means that if the absolute stereochemical configuration of a carbon atom (C atom) directly connected to a substituent Y1 to Y5 or X is an R configuration, the C atoms closest to both sides along the chain backbone of the cyclic compound of the formula (I), which are also directly connected to a substituent Y1 to Y5 or X, have an S configuration.
  • an "alternating stereochemical relative configuration" in the sense of the present invention thus means that if the relative stereochemical configuration of a C atom directly connected to a substituent Y1 to Y5 or X is an L configuration, the C atoms closest to both sides along the chain backbone of the cyclic compound (I), which are also directly connected to a substituent Y1 to Y5 or X, have a D configuration.
  • the CY4 i.e., the C atom directly connected to the substituent Y4
  • CYS and also CYS
  • Cx an L configuration CYI a D configuration
  • CYI a D configuration
  • an “opposite absolute stereochemical configuration” and “same absolute stereochemical configuration” and “opposite relative stereochemical configuration” or “same relative stereochemical configuration” are to be understood in this sense. That is, an “opposite absolute stereochemical configuration", in the sense of the present invention, means that if the one absolute stereochemical configuration is an R configuration, the opposite absolute stereochemical configuration is an S configuration. And an “same absolute stereochemical configuration” in the sense of the present invention means that if the one absolute configuration is an R configuration, the same absolute configuration is also an R configuration. This applies analogously to the relative stereochemical configuration, so that an “opposite relative stereochemical configuration" in the sense of the present invention means that if the one relative stereochemical configuration is a D configuration, the opposite relative stereochemical configuration is an L configuration, etc.
  • the cyclic peptide compound of formula (I) can thus exist in stereoisomeric forms (enantiomers, diastereomers), for example depending on its specific structure.
  • the invention therefore also encompasses the enantiomers or diastereomers and corresponding mixtures thereof.
  • the stereoisomeric unitary components can be isolated in a known manner from such mixtures of enantiomers and/or diastereomers. If the compound of the invention can occur in tautomeric forms, the present invention encompasses all tautomeric forms.
  • the C atom which is directly connected to the substituent X is also connected via a direct bond to a thiazolidine or oxazolidine ring in position 2.
  • the C atom which is directly connected to the substituent X and the C atom in position 4 of the thiazolidine or oxazolidine ring have the same absolute stereochemical configuration when Z is O (i.e. if it is an oxazolidine ring) and an opposite absolute stereochemical configuration when Z is S (i.e. if it is a thiazolidine ring).
  • the terms "opposite absolute stereochemical configuration” and “same absolute stereochemical configuration” are to be understood as defined above.
  • Preferred salts for the purposes of the present invention are physiologically (in particular cosmetically) acceptable salts of the compound of formula (I) according to the invention. However, they also include salts which are not themselves suitable for cosmetic applications but can be used, for example, to isolate or purify the compound of formula (I) according to the invention.
  • Examples of cosmetically acceptable salts of the cyclic compound of formula (I) include salts of inorganic bases such as ammonium salts, alkali metal salts, in particular sodium or potassium salts, alkaline earth metal salts, in particular magnesium or calcium salts; salts of organic bases, in particular salts derived from cyclohexylamine, Benzylamine, octylamine, ethanolamine, diethanolamine, diethylamine, triethylamine, ethylenediamine, procaine, morpholine, pyrroline, piperidine, N-ethylpiperidine, N-methylmorpholine, piperazine as organic base; or salts with basic amino acids, in particular lysine, arginine, ornithine and histidine.
  • inorganic bases such as ammonium salts, alkali metal salts, in particular sodium or potassium salts, alkaline earth metal salts, in particular magnesium or calcium salts
  • salts of organic bases in particular salt
  • Examples of cosmetically acceptable salts of the compound of formula (I) also include salts of inorganic acids such as hydrochlorides, hydrobromides, sulfates, phosphates or phosphonates; salts of organic acids, in particular acetates, formates, propionates, lactates, citrates, fumarates, maleates, benzoates, tartrates, malates, methanesulfonates, ethanesulfonates, toluenesulfonates or benzenesulfonates; or salts with acidic amino acids, in particular aspartate or glutamate.
  • inorganic acids such as hydrochlorides, hydrobromides, sulfates, phosphates or phosphonates
  • salts of organic acids in particular acetates, formates, propionates, lactates, citrates, fumarates, maleates, benzoates, tartrates, malates, methanesulfonates, ethane
  • Solvates in the sense of the invention refer to those forms of the compound of the formula (I) according to the invention which form a complex in the solid or liquid state by coordination with solvent molecules. Hydrates are a special form of solvates in which coordination takes place with water.
  • the compound of the formula (I) according to the invention can also be complexed, e.g. with iron, calcium, etc., where the compound of the formula (I) can act as a ligand, so that corresponding complexes are also the subject of the present invention.
  • the substituent X is selected from the group consisting of ethyl, n-propyl, 2-propenyl, 1-methylethyl, n-butyl, 2-methylpropyl, 1-methylpropyl, 1,1-dimethylethyl, n-pentyl, 3-methylbutyl, benzyl, propargyl, 1N-methyl-1/7-indol-3-ylmethyl, 3-benzothienylmethyl, 1-naphthylmethyl, 9-anthracenylmethyl and pyrenylmethyl (where pyrenylmethyl is preferably selected as 1-pyrenylmethyl or 2-pyrenylmethyl, particularly preferably 1-pyrenylmethyl).
  • X is selected from the group consisting of n-propyl, 1-methylethyl, n-butyl, 2-methylpropyl, 1-methylpropyl, 1,1-dimethylethyl, benzyl, propargyl, and pyrenylmethyl (preferably 1-pyrenylmethyl or 2-pyrenylmethyl, particularly preferably 1-pyrenylmethyl).
  • X is selected from the group consisting of 1-methylethyl, 2-methylpropyl, 1-methylpropyl, 1,1-dimethylethyl, benzyl, propargyl, and pyrenylmethyl (preferably 1-pyrenylmethyl or 2-pyrenylmethyl, particularly preferably 1-pyrenylmethyl).
  • X is selected from the group consisting of n-propyl, 1-methylethyl, n-butyl, 2-methylpropyl, 1-methylpropyl, 1,1-dimethylethyl, n-pentyl and 3-methylbutyl.
  • the substituents Y1 to Y5 are each selected from the group consisting of methyl, ethyl, n-propyl, 2-propenyl, 1-methylethyl, n-butyl, 2-methylpropyl, 1-methylpropyl, 1,1-dimethylethyl, benzyl, propargyl, 1/7-indol-3-ylmethyl, 1/V-methyl-1/7-indol-3-ylmethyl, 3-benzothienylmethyl, 1-naphthylmethyl, 9-anthracenylmethyl, and pyrenylmethyl (preferably 1-pyrenylmethyl or 2-pyrenylmethyl, particularly preferably 1-pyrenylmethyl).
  • Y1 to Y5 are each selected from the group consisting of methyl, 1-methylethyl, 2-methylpropyl, 1-methylpropyl, benzyl, 1/7-indol-3-yl-methyl, propargyl, and pyrenylmethyl (preferably 1-pyrenylmethyl or 2-pyrenylmethyl, particularly preferably 1-pyrenylmethyl).
  • preferred radicals for Y2 are 1/7-1ndol-3-ylmethyl, 1/V-methyl-1/7-indol-3-ylmethyl, 3-benzothienylmethyl, 1-naphthylmethyl, 9-anthracenylmethyl, and pyrenylmethyl (preferably 1-pyrenylmethyl or 2-pyrenylmethyl, particularly preferably 1-pyrenylmethyl), more preferably 1/7-1ndol-3-ylmethyl or pyrenylmethyl (preferably 1-pyrenylmethyl or 2-pyrenylmethyl, particularly preferably 1-pyrenylmethyl), in which case Y5 is preferably not an aromatic radical (in particular is not 1/7-1ndol-3-ylmethyl or pyrenylmethyl).
  • preferred radicals for Y3 are n-propyl, 1-methylethyl, n-butyl, 2-methylpropyl, 1-methylpropyl and 1,1-dimethylethyl, particularly preferred is 2-methylpropyl.
  • preferred radicals for Y4 are methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 2-methylpropyl, 1-methylpropyl, 1,1-dimethylethyl, particularly preferred is 1-methylethyl.
  • preferred radicals for Y5 are 1/7-1ndol-3-ylmethyl, 1/V-methyl-1/7-indol-3-ylmethyl, 3-benzothienylmethyl, 1-naphthylmethyl, 9-anthracenylmethyl, and pyrenylmethyl (preferably 1-pyrenylmethyl or 2-pyrenylmethyl, particularly preferably 1-pyrenylmethyl), more preferably 1/7-1ndol-3-ylmethyl or pyrenylmethyl (preferably 1-pyrenylmethyl or 2-pyrenylmethyl, particularly preferably 1-pyrenylmethyl), for example particularly preferably 1/7-indol-3-ylmethyl, in which case Y2 is preferably not an aromatic radical (in particular is not 1/7-1ndol-3-ylmethyl or pyrenylmethyl).
  • Y2 is 1/7-indol-3-ylmethyl or pyrenylmethyl (preferably 1-pyrenylmethyl or 2-pyrenylmethyl, particularly preferably 1-pyrenylmethyl) if Y5 is 1-methylethyl, or Y2 is 1-methylethyl if Y5 is 1/7-indol-3-ylmethyl or pyrenylmethyl (preferably 1-pyrenylmethyl or 2-pyrenylmethyl, particularly preferably 1-pyrenylmethyl).
  • Y2 is 1/7-indol-3-ylmethyl or pyrenylmethyl (preferably 1-pyrenylmethyl or 2-pyrenylmethyl, particularly preferably 1-pyrenylmethyl), and Y5 is 1-methylethyl, or Y2 is 1- Methylethyl, and Y5 is 1/7-1 ndol-3-ylmethyl or pyrenylmethyl (preferably 1-pyrenylmethyl or 2-pyrenylmethyl, particularly preferably 1-pyrenylmethyl).
  • Z is S. In an alternative preferred embodiment of the cyclic compound of formula (I) according to the invention, Z is O.
  • R and R' are each selected from the group consisting of H, methyl, ethyl, n-propyl, 1-methylethyl, benzyl and propargyl.
  • R and R' are each selected from the group consisting of H, methyl, ethyl and propargyl.
  • R and R' are both methyl.
  • R is H; and R' is methyl, ethyl, n-propyl, 1-methylethyl, benzyl or propargyl.
  • X is selected from the group consisting of 1-methylethyl, 2-methylpropyl, 1-methylpropyl, benzyl, propargyl, pyrenylmethyl (preferably 1-pyrenylmethyl or 2-pyrenylmethyl, particularly preferably 1-pyrenylmethyl); Yi to Ys are each selected from the group consisting of methyl, ethyl, n-propyl, 1-methylethyl, 2-methylpropyl, 1-methylpropyl, benzyl, 1/7-indol-3-yl-methyl, propargyl, pyrenylmethyl (preferably 1-pyrenylmethyl or 2-pyrenylmethyl, particularly preferably 1-pyrenylmethyl); Z is O or S; and/or R and R' are each selected from the group consisting of H, methyl, ethyl, and propargyl, with the proviso that when R is H, R' is not H.
  • the cyclic compound of formula (I), wherein either the substituent Y2 or the substituent Y5, but preferably not in positions Y2 and Y5 simultaneously, is a pyrenylmethyl, has a high non-selective antimicrobial, in particular non-selective antibacterial, activity compared to a cyclic compound of formula (I) wherein the substituent Y2 or the substituent Y5 is a 1/7-indol-3-ylmethyl.
  • the substituent Y2 or the substituent Y5 is a pyrenylmethyl (preferably 1-pyrenylmethyl or 2-pyrenylmethyl, particularly preferably 1-pyrenylmethyl).
  • either the substituent Y2 or the substituent Y5 is pyrenylmethyl (preferably 1-pyrenylmethyl or 2-pyrenylmethyl, particularly preferably 1-pyrenylmethyl), and preferably no other substituent X and Y1 to Y5 is a pyrenylmethyl.
  • R and R' are both methyl; Y2 is 1/7-1 ndol-3-ylmethyl or pyrenylmethyl if Y5 is 1-methylethyl, or Y2 is 1-methylethyl if Y5 is 1/7-1 ndol-3-ylmethyl or pyrenylmethyl; and X is 1-methylethyl.
  • R and R' are both methyl; Y2 is 1/7-1 ndol-3-ylmethyl or pyrenylmethyl, and Y5 is 1-methylethyl, or Y2 is 1-methylethyl and Y5 is 1 H-indol-3-ylmethyl or pyrenylmethyl; X is 1-methylethyl; and Z is preferably S.
  • the pyrenylmethyl is preferably 1-pyrenylmethyl or 2-pyrenylmethyl, particularly preferably 1-pyrenylmethyl.
  • R is H; R' is methyl, ethyl, n-propyl, 1-methylethyl, benzyl or propargyl; Y2 is 1/7-1 ndol-3-ylmethyl or pyrenylmethyl if Y5 is 1-methylethyl, or Y2 is 1-methylethyl if Y5 is 1/7-1 ndol-3-ylmethyl or pyrenylmethyl; X is 1-methylethyl; and Z is preferably S.
  • R is H; R' is methyl, ethyl, n-propyl, 1-methylethyl, benzyl or propargyl; Y2 is 1/7-1 indol-3-ylmethyl or pyrenylmethyl, and Y5 is 1-methylethyl, or Y2 is 1-methylethyl, and Y5 is 1/7-indol-3-ylmethyl or pyrenylmethyl; X is 1-methylethyl; and Z is preferably S.
  • the pyrenylmethyl is preferably 1-pyrenylmethyl or 2-pyrenylmethyl, in particular 1-pyrenylmethyl.
  • R is H; R' is methyl, n-propyl, 1-methylethyl, benzyl or propargyl; Y2 is 1/7-1 ndol-3-ylmethyl or pyrenylmethyl if Y5 is 1-methylethyl, or Y2 is 1-methylethyl if Y5 is 1/7-1 ndol-3-ylmethyl or pyrenylmethyl; X is 1-methylethyl or 2-methylpropyl.
  • R is H; R' is methyl, n-propyl, 1-methylethyl, benzyl or propargyl; Y2 is 1/7-1 ndol-3-ylmethyl or pyrenylmethyl, and Y5 is 1-methylethyl, or Y2 is 1-methylethyl, and Y5 is 1/7-1 ndol-3-ylmethyl or pyrenylmethyl; X is 1-methylethyl or 2-methylpropyl.
  • the pyrenylmethyl is preferably 1-pyrenylmethyl or 2-pyrenylmethyl, particularly preferably 1-pyrenylmethyl.
  • R and R' are both 1-methylethyl; and Y2 is 1/7-indol-3-ylmethyl.
  • R and R' are each H or methyl; Y2 is 1/7-indol-3-yl; and X is 1-methylethyl.
  • the C atom which is directly connected to the substituent Y5 is in an (absolute) S configuration (i.e. L configuration).
  • the cyclic compound of formula (I) is characterized by one of the following formulae 1.1a to 1.24a:
  • cyclic compounds of the formula 1.1a to 1.4a or 1.1 to 1.4 are particularly preferred.
  • the cyclic compounds of the formula 1.19a to 1.24a or 1.19 to 1.25 are particularly preferred.
  • an oxazolidine ring is present instead of a thiazolidine ring.
  • antimicrobial peptide having the structure
  • This preferably selected peptide is referred to according to the invention as ISW1-2. It surprisingly has advantageous antibacterial effects.
  • ISW1-2 is a fully synthetic peptide made of D- and L-amino acids that cyclize via a thiazolidine ring. It is a derivative of the natural substance lugdunin, which is produced by the skin-commensal bacterium Staphylococcus lugdunensis, which occurs naturally in the human nose, among other places.
  • This peptide is particularly noteworthy.
  • the antibacterial effect correlates strongly with the collapse of the membrane potential of the bacteria.
  • No specific target is addressed, because the enantiomer of the peptide has the same antimicrobial effectiveness, which rules out a stereospecific interaction with a target molecule.
  • the mechanism of action is based on proton translocation while maintaining membrane integrity.
  • the peptide supports the innate immune response of the skin, in synergy with the factors derived from the host and microbiome, so that pathogenic germs are combated at various levels and recolonization, e.g. with S. aureus, can be counteracted.
  • the antimicrobial peptides in particular ISW1-2, show a synergistic antimicrobial effect.
  • Flavonoids are advantageously chosen as combination partners for AMPs.
  • Licochalcone A, Licochalcone C, Licochalcone E and/or Glabrol, especially Licochalcone A, are advantageously chosen as flavonoids.
  • extracts, solutions, mixtures containing these flavonoids can also be used, such as the plant extract Glycyrrhiza inflata.
  • Licochalcone A has the structure:
  • flavonoids include Licochalcone C and Glabrol.
  • the topical preparation according to the invention thus preferably contains flavonoids, flavonoid-containing extracts, flavonoid-containing solutions and/or flavonoid-containing mixtures, wherein the flavonoids are in particular licochalcones, and preferably licochalcone A, licochalcone C, licochalcone E and/or glabrol.
  • the preparation contains the peptide with the structure cyclo[N-DVal-LTrp-DLeu-LVal-DTrp-LMe 2 Thz(LVal)-C], ie the peptide ISW1-2, and one or more licochalcones from the group Licochalcone A, Licochalcone C, Licochalcone E and/or Glabrol.
  • the preparation contains the peptide ISW1-2 and Licochalcone A. In a further preferred embodiment of the invention, the preparation contains the peptide ISW1-2 and Licochalcone C. In a further preferred embodiment of the invention, the preparation contains the peptide ISW1-2 and Licochalcone E. In a further preferred embodiment of the invention, the preparation contains the peptide ISW1-2 and Glabrol.
  • ISW1-2 has antimicrobial activity against gram-positive bacteria in vitro even at very low concentrations (3.1 g/ml against Staphylococcus aureus).
  • skin pathogens such as Staphylococcus aureus, whose increase correlates with the severity of atopy and is also proven to be associated with Cutibacterium acnes in acne, were particularly sensitive to this active ingredient.
  • ISW1-2 exhibits antimicrobial activity even in the micromolar range.
  • the minimum inhibitory concentration (MIC) of ISW1-2 for Staphylococcus aureus is 3.1 g/ml (0.00031%).
  • proportions of one or more AMPs, in particular ISW1-2 are selected in the range from 0.00001% by weight to 1.0% by weight, preferably 0.0001% by weight to 0.5% by weight, in particular 0.0003% by weight to 0.3% by weight, based on the total mass of the preparation, advantageously in cosmetic formulations.
  • proportions of one or more AMPs, in particular ISW1-2 are selected in the range from 0.00001% by weight to 1.0% by weight, preferably 0.0001% by weight to 0.5% by weight, in particular 0.0003% by weight to 0.3% by weight, based on the total mass of the preparation, advantageously in cosmetic formulations.
  • Another advantage is that by reducing the effective amounts, the costs of manufacturing and introducing these active ingredients can also be reduced. The resulting cost reduction also allows for a wider range of cosmetic uses.
  • the combination partners selected from skin-soothing substances, skin barrier-strengthening substances and/or flavonoids, are advantageously used in a proportion in the range of 0.0001% by weight to 5% by weight, based on the total mass of the preparation, whereby the information in % by weight refers in particular to the sum of the combination partners in the total mass of the preparation.
  • 0.0001 to 5% by weight, in particular 0.001 to 1% by weight, very particularly 0.005 to 0.15% by weight of these combination substances are selected, in each case based on the total weight of the preparation, in particular licochalcones, preferably licochalcones A or extracts containing licochalcones.
  • the information in % by weight refers in particular to the sum of the combination substances in the total weight of the preparation.
  • the preparation according to the invention comprises one or more AMPs in an amount of 0.00001% by weight to 1.0% by weight, preferably 0.0001% by weight to 0.5% by weight, in particular 0.0003% by weight to 0.3% by weight, based on the total mass of the preparation, and one or more flavonoids selected from the group consisting of licochalcone A, licochalcone C, licochalcone E and glabrol in an amount of 0.0001 to 5% by weight, in particular 0.001 to 1% by weight, very particularly 0.005 to 0.15% by weight, based on the total mass of the preparation.
  • the preparation according to the invention comprises an AMP in an amount of 0.00001% by weight to 1.0% by weight, preferably 0.0001% by weight to 0.5% by weight, in particular 0.0003% by weight to 0.3% by weight, based on the total mass of the preparation, and a flavonoid selected from the group consisting of licochalcone A, licochalcone C, licochalcone E and glabrol in an amount of 0.0001 to 5% by weight, in particular 0.001 to 1% by weight, very particularly 0.005 to 0.15% by weight, based on the total mass of the preparation.
  • an AMP in an amount of 0.00001% by weight to 1.0% by weight, preferably 0.0001% by weight to 0.5% by weight, in particular 0.0003% by weight to 0.3% by weight, based on the total mass of the preparation
  • a flavonoid selected from the group consisting of licochalcone A, licochalcone C, licochalcone E and glabrol in an amount of
  • the preparation according to the invention comprises the peptide ISW1-2 in an amount of 0.00001 wt.% to 1.0 wt.%, preferably 0.0001 wt.% to 0.5 wt.%, in particular 0.0003 wt.% to 0.3 wt.%, based on the total mass of the preparation, and Licochalcone A in an amount of 0.0001 to 5 wt.%, in particular 0.001 to 1 wt.%, very particularly 0.005 to 0.15 wt.%, based on the total mass of the preparation.
  • the preparation according to the invention comprises the peptide ISW1-2 in an amount of 0.00001 wt.% to 1.0 wt.%, preferably 0.0001 wt.% to 0.5 wt.%, in particular 0.0003 wt.% to 0.3 wt.%, based on the total mass of the preparation, and Licochalcone C in an amount of 0.0001 to 5 wt.%, in particular 0.001 to 1 wt.%, very particularly 0.005 to 0.15 wt.%, based on the total mass of the preparation.
  • the preparation according to the invention comprises the peptide ISW1-2 in an amount of 0.00001 wt.% to 1.0 wt.%, preferably 0.0001 wt.% to 0.5 wt.%, in particular 0.0003 wt.% to 0.3 wt.%, based on the total mass of the preparation, and Licochalcone E in an amount of 0.0001 to 5 wt.%, in particular 0.001 to 1 wt.%, very particularly 0.005 to 0.15 wt.%, based on the total mass of the preparation.
  • the preparation according to the invention comprises the peptide ISW1-2 in an amount of 0.00001 wt.% to 1.0 wt.%, preferably 0.0001 wt.% to 0.5 wt.%, in particular 0.0003 wt.% to 0.3 wt.%, based on the total mass of the preparation, and Glabrol in an amount of 0.0001 to 5 wt.%, in particular 0.001 to 1 wt.%, very particularly 0.005 to 0.15 wt.%, based on the total mass of the preparation.
  • inventive preparations show synergistic effects, so that even at low concentrations of antimicrobial peptides, in particular ISW1-2, the antimicrobial effectiveness against atopic dermatitis and/or acne-associated skin germs (Staphylococcus aureus, Cutibacterium acnes) is guaranteed. Surprisingly, this synergistic effect occurs with the pathogenic germs S. aureus and C. acnes, but not with the skin commensal germ S. epidermidis.
  • ISW1-2 and flavonoids advantageously Licochalcone A
  • an antimicrobial combination was found that It minimizes excessive S. aureus colonization, is not cytotoxic to skin cells (keratinocytes) and is stable against proteolytic degradation of the skin's own enzymes.
  • Soothing the skin means reducing or completely avoiding skin irritation, itching, tension and/or redness.
  • Strengthening the skin barrier means building up a protective skin film, promoting the cohesion of the skin and/or minimizing or preventing harmful external influences.
  • the barrier is the outermost layer of the skin that provides protection, retains moisture and protects against external irritants such as bacteria, allergens and environmental influences.
  • substances that have these properties are skin-soothing or skin barrier-strengthening substances.
  • one or more substances are preferably selected from the group comprising
  • Vitamins especially vitamin A, B5, E
  • Plant extracts such as marigold, witch hazel, oats
  • preparations are advantageously provided which, in addition to antimicrobial peptides, in particular ISW1-2, licochalcones, in particular licochalcones A, C and/or E, glabrol or extracts, solutions or mixtures containing them. It is advantageous if one or more substances from the group of skin-soothing substances and/or substances which strengthen the skin barriers are also additionally included. If an active ingredient belongs to both the skin-soothing substance group and the group of substances that strengthen the skin barrier, then an embodiment that is intended to include substances from both groups will also contain two or more different substances from both groups.
  • the growth of disruptive bacteria is significantly inhibited and at the same time beneficial bacteria (S. epidermides), which stabilize the skin microbiome, are left undisturbed.
  • the topically applicable preparation according to the invention is a cosmetic and/or dermatological preparation, preferably based on an emulsion.
  • topically applicable preparations according to the invention there are various possible uses for the topically applicable preparations according to the invention.
  • the non-therapeutic use of the preparation according to the invention for the treatment of inflammatory skin diseases and/or indications, in particular acne, rosacea and/or atopic dermatitis, is therefore particularly advantageous.
  • the preparation according to the invention can advantageously be used for skin care, in particular for the care, prophylaxis and treatment of skin damaged by atopic dermatitis or acne.
  • the preparation according to the invention can also be used advantageously in the treatment of atopic dermatitis, acne and/or allergic contact dermatitis.
  • the preparation according to the invention can also be used advantageously in wound healing and for the care of hypersensitive skin.
  • the invention therefore also relates to a non-therapeutic, in particular cosmetic, method for skin treatment, in which the topically applicable preparation according to the invention is applied to the skin.
  • the non-therapeutic skin treatment is preferably for the care of the skin, to support wound healing of the skin and/or to treat skin damaged by atopic dermatitis or acne.
  • the non-therapeutic skin treatment is for the care of the skin, in particular for the care of hypersensitive skin.
  • the invention relates to a substance combination of one or more antimicrobial peptides and one or more substances selected from the group of skin-soothing Substances that strengthen the skin barrier and/or flavonoids for use in the treatment of inflammatory skin diseases and/or indications, in particular acne, rosacea and/or atopic dermatitis.
  • Cyclic peptide compounds based on the synthesis of thiazolidine and oxazolidine building blocks are preferably selected as peptides in the substance combination.
  • the topical preparation according to the invention contains flavonoids, flavonoid-containing extracts, flavonoid-containing solutions and/or flavonoid-containing mixtures, wherein the flavonoids are in particular licochalcones, particularly preferably licochalcone A, licochalcone C, licochalcone E and/or glabrol.
  • the substance combination according to the invention is used in a cosmetic and/or dermatological preparation.
  • a topically applicable preparation can now be made available which leads in particular to a reduction of the pathogenic germs S. aureus and C. acnes and at the same time achieves a balancing of the skin commensal germ S. epidermidis. This leads to an improvement in the condition of the skin, especially in the case of skin damaged by acne or atopic dermatitis.
  • the unpleasant bacteria such as Propionibacterium acnes
  • the pleasant bacteria such as Staphylococcus epidermidis
  • “selective” means a reduction in anaerobic bacteria and little (preferably no) reduction in aerobic bacteria. According to the invention, the combination is advantageously used in cosmetic or dermatological preparations.
  • preparations according to the invention can be used in a variety of application forms.
  • Preferred application forms are gels, sprays, serums, impregnation medium for impregnated patches, wipes or masks.
  • the sophisticated cosmetic compositions according to the invention can optionally comprise other conventional auxiliaries and additives, such as, for example, consistency agents, fillers, perfumes, dyes, active ingredients, vitamins, proteins, light stabilizers, stabilizers, insect repellents, salts, EDTA, other antimicrobial, proteolytic or keratolytic substances, etc., provided they are not excluded according to the invention.
  • auxiliaries and additives such as, for example, consistency agents, fillers, perfumes, dyes, active ingredients, vitamins, proteins, light stabilizers, stabilizers, insect repellents, salts, EDTA, other antimicrobial, proteolytic or keratolytic substances, etc.
  • one or more active ingredients from the following groups are preferably added to the preparations in order to ensure the widest possible range of applications and individual care and treatment.
  • active ingredients can be added to the preparations or application forms according to the invention, provided that they are not mentioned in the substance groups according to the invention, such as preferably sebum-reducing active ingredients, anti-itching active ingredients, anti-inflammatory, healing-stimulating, pain-relieving or antimicrobial active ingredients, such as dexpanthenol, or natural additives, natural substances, such as honey, chamomile or aloe vera.
  • vitamins such as vitamin A, C or E
  • additional active ingredients include growth factors such as PDGF, sugars or polysaccharides such as glucose, minerals such as zinc, amino acids and their derivatives such as arginine or creatine.
  • cell membrane-addressing active ingredients such as quats, octenidines or decanediol.
  • natural substances such as cyclic and non-cyclic peptides of ribosomal and non-ribosomal (NRPS-derived) origin as well as cyclic and non-cyclic polyketides (PKS-derived) are advantageously added according to the invention.
  • Other preferred active ingredients are enzymes, especially cell wall hydrolytic enzymes such as endolysins, lysozyme, chitinases, provided they are compatible with the peptide and do not attack it.
  • Particularly preferred is the addition of one or more active ingredients selected from the group hydroxyacetophenone, salicylic acid, Q10 and/or thiamidol.
  • additives can be selected from Ca, Mg, Al, and/or Zn salts.
  • Other preferred active ingredients can be selected from Magnolia, Arctiin, Bioxilift, Creatine, Isoflavones, Laminaria, NAHP, Phloridzin, Vitamin C, Lotus Extract, Myriceline, White Tea, AGR, Glycyrrhetinic Acid, Silymarin S, Tocopheryl, Carnitine, Garcinia Cambogia, Guarana C22, Butyloctanoic Acid, Dioic, Ethylhexylglycerin, Methyl Phenylbutanol, Polyglyceryl-2 Caprate, Polysaf 5600 Polymer, Silver Citrate, Zinc Citrate, Betaine, Sea Salt, Taurine, SymSave H, DHA, Rucinol, Panthenol/Dexpanthenol.
  • acnes DSM 1897 was incubated under anaerobic conditions at 37°C. The overnight culture was cultured 1:1000 in Caso Medium (casein peptone 17g/l; soy flour peptone 3g/l;
  • the quantities refer to the weight of the substance per volume of the medium, e.g. 1 pg/ml means 1 pg Licochalcone A in 1 ml of medium.
  • the percentage quantities of ISW1-2 refer to the weight of ISW1-2 in relation to the total weight of the respective test batch.
  • Glycyrrhiza inflata Extract which contains 21 wt.% Licochalcone A, was used as Licochalcone A Extract.
  • a non-inhibitory amount of an antimicrobial peptide (ISW1-2) is then able to have an inhibitory effect on C. acnes by adding Licochalcone A (Fig. 1 and 2 right bars, black).
  • the pure extract or pure Licochalcone A only has a lower inhibitory effect (Fig. 1 and 2 left bars, hatched).
  • S. aureus DSM20231 and S. epidermidis ATTC 12228 were incubated under aerobic conditions at 37°C with constant shaking.
  • the overnight cultures were diluted 1:10000 in MHB (Müller Hinton Broth: starch 1.5g/l; meat infusion 2.0g/l; peptone from casein (hydrolyzed) 17.5g/l; pH: 7.4 ⁇ 0.2) and seeded in microtiter plates.
  • Different concentrations of the plant extract Glycyrrhiza inflata and the flavonoids licochalcones A, C, and E (1 g/ml, 2pg/ml) were added, mixed and bacterial growth was observed at 37°C for 24 h.
  • Figures 3 to 10 show the bacterial growth over 24 hours under the different conditions (average values from three independent experiments).
  • Bacterial growth is measured by the increase in turbidity in the medium (OD600), i.e. an increase in OD over time signals bacterial growth.
  • Figure 3 shows the bacterial growth upon addition of Licochalcone A extract (0%, control) and a relatively slight growth delay upon addition of 1 pg or 2 pg.
  • Figure 4 shows the bacterial growth when pure non-inhibitory ISW1-2 was added (0.00002%, control) and the growth when Licochalcone A extract was added to ISW1-2 (1 pg/ml, 2 pg/ml).
  • Figures 7 and 8 show the investigations with ISW1-2 and Licochalcone C.
  • Licochalcone C Four different amounts of Licochalcone C were used (0%, control; 1 pg/ml; 2 pg/ml and 4 pg/ml), alone ( Figure 7) and with 0.00002% ISW1-2 (Figure 8).
  • Licochalcone C is slightly less synergistic with ISW1-2 than Licochalcone A, the synergism is present and sufficient to influence bacterial growth (Figure 8).
  • the concentration of the cooperation partner, here Licochalcone C must be increased (e.g. to 4pg/ml) in order to completely inhibit S. aureus growth.
  • Figures 9 and 10 show the investigations with ISW1-2 and Licochalcone E.
  • Three different amounts of Licochalcone E were used (0%, control; 1 pg/ml; 2 pg/ml), alone ( Figure 9) and with 0.00002% ISW1-2 ( Figure 10).
  • Licochalcone E in turn, has a better synergistic effect with ISW1-2, similar to Licochalcone A, and no growth of S. aureus was observed in the substance combination according to the invention (Figure 10).
  • Staphylococcus epidermidisl 2228 was incubated without ISW1-2 ( Figures 11 , 13, 15, 17) and with a non-inhibitory concentration of 0.00002% ISW1-2 ( Figures 12, 14, 16, 18) using different concentrations of Licochalcone Extract;
  • Bacterial growth is measured by the increase in turbidity in the medium (OD600), i.e. an increase in OD over time signals bacterial growth.
  • the first preparation was a control preparation that only contained the carrier composition (vehicle).
  • the second preparation (+ISW1-2) contained the carrier composition and 0.015% ISW1-2.
  • the third preparation (+ISW1-2 +LicoExtr.) contained the carrier composition, 0.015% ISW1-2 and additionally 0.025% LicoExtract (Glycyrrhiza inflata extract with 21% by weight Licochalcone A).
  • the three preparations were tested on 6 volunteers with healthy skin.

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Abstract

L'invention concerne une préparation à application topique comprenant une combinaison de substances comprenant des peptides antimicrobiens (AMP), en particulier des composés peptidiques cycliques basés sur la synthèse de composants thiazolidine et oxazolidine, ainsi que des substances apaisantes pour la peau, telles que le menthoxypropanédiol, des substances pour renforcer la barrière cutanée, telles que des acides gras oméga-6, et/ou des flavonoïdes tels que la licochalcone, qui agissent de manière synergique et sélective contre des bactéries pathogènes, telles que S. aureus et C. acnes, mais non contre des bactéries commensales cutanées, telles que S. epidermidis. Les préparations peuvent être utilisées avantageusement pour le traitement de l'acné ou de la dermatite atopique et pour soigner la peau qui a été endommagée par l'acné ou la dermatite atopique.
PCT/EP2023/079024 2022-10-18 2023-10-18 Préparation appliquée par voie topique pour améliorer l'état de la peau WO2024083930A1 (fr)

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DE102022210999.6A DE102022210999A1 (de) 2022-10-18 2022-10-18 Topisch applizierbare Zubereitung zur Verbesserung des Hautzustandes
DE102022210999.6 2022-10-18
PCT/EP2023/075256 WO2024083413A1 (fr) 2022-10-18 2023-09-14 Préparation à application topique avec des peptides antimicrobiens
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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102006010589A1 (de) * 2006-03-06 2007-09-13 Beiersdorf Ag Kosmetische oder dermatologische Emulsionen enthaltend Licocalchon A oder einen Licocalchon A enthaltenden Extraxt aus Radix Glycyrrhizae inflatae
US20120237624A1 (en) * 2009-11-30 2012-09-20 Laboratoires Expanscience Vigna unguiculata seed extract and compositions containing same
WO2022106667A1 (fr) 2020-11-20 2022-05-27 Eberhard Karls Universität Tübingen Nouveaux composés cycliques, leur procédé de production et leur utilisation dans des préparations cosmétiques

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102006010589A1 (de) * 2006-03-06 2007-09-13 Beiersdorf Ag Kosmetische oder dermatologische Emulsionen enthaltend Licocalchon A oder einen Licocalchon A enthaltenden Extraxt aus Radix Glycyrrhizae inflatae
EP1839645A1 (fr) 2006-03-06 2007-10-03 Beiersdorf AG Emulsions cosmétiques ou dermatologiques comportant du licocalchone A ou un extrait comprenant du licocalchone A à partir de radix glycyrrhizae inflatae
US20120237624A1 (en) * 2009-11-30 2012-09-20 Laboratoires Expanscience Vigna unguiculata seed extract and compositions containing same
WO2022106667A1 (fr) 2020-11-20 2022-05-27 Eberhard Karls Universität Tübingen Nouveaux composés cycliques, leur procédé de production et leur utilisation dans des préparations cosmétiques

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
W. UMBACH: "Kosmetik, Entwicklung, Herstellung und Anwendung kosmetischer", 1995, THIEME VERLAG

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