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EP2470174A1 - Use of faa and its derivatives in cosmetics and dermatology - Google Patents

Use of faa and its derivatives in cosmetics and dermatology

Info

Publication number
EP2470174A1
EP2470174A1 EP10742099A EP10742099A EP2470174A1 EP 2470174 A1 EP2470174 A1 EP 2470174A1 EP 10742099 A EP10742099 A EP 10742099A EP 10742099 A EP10742099 A EP 10742099A EP 2470174 A1 EP2470174 A1 EP 2470174A1
Authority
EP
European Patent Office
Prior art keywords
oxo
benzopyran
skin
acetic acid
formula
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Withdrawn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
EP10742099A
Other languages
German (de)
French (fr)
Inventor
Soheila Anzali
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.)
Merck Patent GmbH
Original Assignee
Merck Patent GmbH
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 Merck Patent GmbH filed Critical Merck Patent GmbH
Priority to EP10742099A priority Critical patent/EP2470174A1/en
Publication of EP2470174A1 publication Critical patent/EP2470174A1/en
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
    • A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
    • 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
    • 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
    • A61P17/06—Antipsoriatics
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/12—Keratolytics, e.g. wart or anti-corn preparations
    • 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
    • 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
    • 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
    • A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
    • 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
    • A61Q19/08—Anti-ageing preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00—Preparations for affecting hair growth

Definitions

  • compositions preferably compositions for topical use, comprising one or more compounds of formula (I), which preferably are flavone acetic acid and/or derivatives thereof, selected from
  • Z is O, S or NH
  • R 1 , R 2 and R 3 are independently of each other selected from
  • hydroxyl group may be bonded to a primary or secondary carbon atom of the chain and furthermore the alkyl chain may also be interrupted by oxygen, preferably hydroxymethyl and hydroxyethyl groups;
  • Ci- to C 2 o-carboxyl groups preferably C 1 - to C 6 -carboxyl groups
  • a salt or solvate thereof preferably as active ingredient, and optionally one or more topically acceptable vehicles.
  • the one or more compounds according to formula (I) are selected from compounds of formula (II)
  • R 1 , R 2 and R 3 are independently of each other selected from
  • EP0080934 and EP0341104 disclose the disclosures of which are incorporated herein by reference in their entirety.
  • the European patent EP0080934A1 discloses 57 formulas of flavone acetic acid derivatives.
  • FORMULAS thereof have been selected as preferred specific examples for the compounds according to formula (I) of the present invention:
  • the European patent EP0341104B1 discloses 131 formulas of flavone acetic acid derivatives. Suitable for use according to the invention, the disclosure of which is incorporated in its entirety into this application by reference, the following Formulas thereof have been also selected as preferred specific examples for the compounds according to formula I of the present invention:
  • mitoflaxone 2-(4-oxo-2-phenylchromen-8-yl)acetic acid [IUPAC], 4-oxo-4H-[1]-benzopyran-8-acetic acid, flavone acetic acid or FAA, and/or a salt thereof, is the most preferred compound in the
  • composition especially the composition for topical use, according to the present invention.
  • one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA are used as one or more compounds of a composition in the field of cosmetics and
  • topically applied preferably means that the compositions containing one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA are generally applied on the surface of the body.
  • the surface of the body preferably includes the skin, the hair, especially the hair roots, and/or mucous membranes.
  • a topical application to a certain area of the skin is affecting the area to which it is applied.
  • topically applied should preferably be understood as the opposite of systemically applied.
  • the human skin is subject to certain ageing processes, some of which are attributable to intrinsic processes (chronoageing) and some of which are attributable to exogenous factors (environmental, for example photoageing); see Shapiro et al. Nutrition 2001; 17:839-844.
  • temporary or even lasting changes to the skin picture can occur, such as acne, greasy or dry skin, keratoses, rosaceae, light-sensitive, inflammatory, erythematous, allergic or autoimmune-reactive reactions, such as dermatosis and
  • the exogenous factors include, in particular, sunlight or artificial radiation sources having a comparable spectrum, and compounds which can be formed by the radiation, such as undefined reactive photoproducts, which may also be free-radical or ionic. These factors also include cigarette smoke and the reactive compounds present therein, such as ozone, free radicals, for example the hydroxyl free radical, singlet oxygen and other reactive oxygen or nitrogen compounds which interfere with the natural physiology or morphology of the skin.
  • MMPs matrix metalloproteinases
  • TIMPs tissue inhibitors of matrix
  • the skin contains an extensive network of macromolecules (e.g., polysaccharides and proteins) that make up the extracellular matrix (ECM).
  • ECM extracellular matrix
  • specific cells within the ECM secrete polysaccharide glycosaminoglycans and fibrous proteins (Alberts et al., Molecular Biology of the Cell, p. 802, New York: Garland Publishing, Inc., 1989).
  • Polysaccharide glycosaminoglycans are long, unbranched polysaccharides composed of repeating disaccharide units. These structures are sometimes linked to a core protein to form larger structures known as proteoglycans (Alberts et al., Molecular Biology of the Cell, p. 803, New York: Garland Publishing, Inc., 1989).
  • the fibrous proteins of the ECM consist of structural proteins such as elastin and collagen, which account for about 70% of the dry weight of the dermis (Lahmann et al., Lancet, 357(9260):935-6, 2001), and adhesive proteins such as fibronectin and laminin.
  • the structure of the ECM is typically characterized by
  • ECM components in particular collagen
  • collagen The integrity of ECM components, in particular collagen, is important to ensure that the epidermal layer of the skin firmly anchors to the dermal layer of the skin.
  • Degradation of collagen at the dermo-epidermal junction by proteases weakens dermal adhesion, which eventually leads to the appearance of wrinkles and a reduction in the firmness and elasticity of the skin (Thibodeau, Allured's Cosmetic & Toiletries Magazine, 115(11):75-82, 2000).
  • MMPs Matrix metalloproteases
  • stromelysin which digest collagen, gelatin (denatured collagen) and other components of the ECM, are important in normal development.
  • MMPs gelatinase A
  • MMP-1 interstitial collagenase
  • TMPs tissue inhibitors of metalloprotease
  • MMPs of type I i.e., interstitial collagenase, MMP-1
  • MMP-1 interstitial collagenase, MMP-1
  • UV damage i.e., wrinkling, loss of elasticity and dilation of surface micro-capillary vessels
  • MMPs such as MMP- 9, MMP-3, and MMP-10 to quench reactive free-radicals like superoxide anions and hydroxyl radicals, and/or to chelate elements such as iron and copper to prevent or reduce oxidative stress to the skin.
  • This objective of the present invention is preferably achieved by using one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA in cosmetics and dermatology.
  • the compounds according to formula (I) preferably FAA and/or its derivatives, and especially FAA in cosmetics and dermatology.
  • the transcriptional levels of the genes MMP-9, MMP-10, and MMP-3 show downregulation after four days of treatment with FAA.
  • a statistical analysis of over-represented biological process categories (GeneOntology) among the regulated genes after treatment with FAA indicates down-regulation of the collagen catabolic process and keratinization.
  • One or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA are effective to reduce or prevent aging through the enhancing of collagen and also to treat acne and other skin diseases.
  • One or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA can preferably be shown to be particular useful as anti-ageing, anti-inflammatory and anti-acne ingredients in dermatological and cosmetic compositions (alone or in combination with other actives). Therefore, the invention relates to the use of one or more of the compounds according to formula (I), preferably FAA and/or its
  • the invention also relates to the use of one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA in the preparation of cosmetic compositions for the use as anti-ageing, anti-inflammatory and for the treatment of acne.
  • the invention also relates to the use of one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA in the preparation of cosmetic compositions for the use as modulators of hair growth and/or hair loss and preferably also treatment of hyperpigmentation and/or modulation of pigmentation, including depigmentation.
  • One or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA can be used as free acid but also as one of their salts with organic or inorganic bases, of the salts formed with metals and in particular alkali, alkaline earth and transition metals (such as sodium, potassium calcium, magnesium or aluminium) or with bases, such as ammonia or secondary or tertiary amines (such as diethylamine,
  • FAA can be used in form of its alkali metal salts, preferably its potassium or sodium salt, and especially its sodium salt.
  • compositions or components described are preferably suitable for use in contact with human skin without risk of toxicity, incompatibility, instability and/or allergic response, and the like.
  • composition preferably relates to a formulation that can be used for cosmetic purposes, purposes of hygiene and/or as a basis for delivery of one or more pharmaceutical ingredients. It is also possible that these formulations are used for two or more of these purposes at one time.
  • compositions preferably include without limitation, lipstick, mascara, rouge, foundation, blush, eyeliner, lipliner, lip gloss, facial or body powder, sunscreens and blocks, nail polish, mousse, sprays, styling gels, nail conditioner, whether in the form of creams, lotions, gels, ointments, emulsions, colloids, solutions, suspensions, compacts, solids, pencils, spray- on formulations, brush-on formulations and the like.
  • Personal care products preferably include, without limitation, bath and shower gels, shampoos, conditioners, cream rinses, hair dyes and coloring products, leave-on conditioners, sunscreens and sunblocks, lip balms, skin conditioners, cold creams, moisturizers, hair sprays, soaps, body scrubs, exfoliants, astringents, depilatories and permanent waving solutions, antidandruff formulations, antisweat and antiperspirant compositions, shaving, preshaving and after shaving products, moisturizers, deodorants, cold creams, cleansers, skin gels, rinses, whether in solid, powder, liquid, cream, gel, ointment, lotion, emulsions, colloids, solutions, suspensions, or other form.
  • compositions in accordance with the present invention preferably include, without limitation, carriers for dermatological purposes, including topical and transdermal application of pharmaceutically active ingredients. These can be in the form of gels, patches, creams, nose sprays, ointments, lotions, emulsions, colloids, solutions, suspensions, powders and the like.
  • compositions in accordance with the invention preferably include cosmetics, personal care products and pharmaceutical preparations.
  • Compositions in accordance with the invention especially preferably include cosmetics or personal care products.
  • skin ageing or “signs of skin ageing” preferably include, but are not limited to, all outward visibly and tactilely perceptible manifestations as well as any other macro or micro effects due to skin ageing. Such signs may be induced or caused by intrinsic factors or extrinsic factors, e.g.
  • the signs may result from processes which preferably include, but are not limited to, the
  • textural discontinuities such as wrinkles and coarse deep wrinkles, skin lines, crevices, bumps, large pores (e.g. associated with adnexal structures such as sweat gland ducts, sebaceous glands, or hair follicles), or unevenness or roughness of the skin, loss of skin elasticity (loss and/or in activation of functional skin elastin), sagging (including puffiness in the eye area and jowls), loss of skin firmness, loss of skin tightness, loss of skin recoil from deformation, discoloration (including (black) under eye circles), blotching, sallowness, hyperpigmented skin regions such as age spots and freckles, keratoses, abnormal differentiation, hyperkeratinization, elastosis, collagen breakdown, and other histological changes in the stratum corneum, dermis, epidermis, the skin vascular system (e.g., telangiectasia or spider vessels), and underlying tissues, especially those proxi
  • prophylactically regulating a skin condition preferably includes delaying, minimizing and/or preventing visible and/or tactile discontinuities in skin (e.g., texture irregularities in the skin which may be detected visually or by feel), including signs of skin aging.
  • therapeutically regulating skin condition preferably includes ameliorating, e.g., diminishing, minimizing and/or effacing, discontinuities in skin, including signs of skin aging.
  • compositions of the present invention are useful for improving skin appearance and/or feel of skin exhibiting signs of skin aging.
  • preferred compositions of the present invention are useful for regulating the appearance of skin conditions by providing an immediate visual improvement in skin appearance following application of the composition to the skin.
  • compositions of the present invention which further contain particulate materials will be most useful for providing the immediate visual improvement.
  • Some of the compositions of the present invention may also provide one or more additional benefits, preferably selected from stability of the formulation, absence of significant (consumer-unacceptable) skin irritation, anti- inflammatory activity and/or good aesthetics.
  • the present invention is useful for improving the physiological state and/or the physical appearance of human skin, in particular to reduce the signs of skin aging that are generated by sun exposure, physical and hormonal stress, abrasion, nutritional effects and other similar causes.
  • the compositions may often be used to prevent the signs of aging and/or to treat them in order to afford the consumer who uses them, a more youthful appearance.
  • the instant invention more preferably relates to:
  • a composition preferably a non-therapeutic composition comprising one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA and/or a salt or solvate thereof.
  • composition for topical use comprising
  • one or more further active compounds having a skin-care and/or inflammation-inhibiting action.
  • compositions as described above/below wherein one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA are typically employed in accordance with the invention in amounts of from 0.01 to 20% by weight, preferably in amounts of from 0.1% by weight to 10% by weight and particularly preferably in amounts of from 1 to 8% by weight.
  • a composition comprising one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA and at least one further skin-care ingredient and at least one carrier which is suitable for topical applications.
  • ichthyosiform states Darier's disease, keratosis palmoplantaris, leukoplakia, leukoplakiform states, skin and mucosal (buccal) eczema (lichen), for the treatment of other skin diseases which are associated with defective keratinisation and have an inflammatory and/or immunoallergic component, and in particular all forms of psoriasis relating to the skin, mucous
  • FAA and/or its derivatives and especially FAA for the prophylaxis against or reduction of skin unevenness, such as wrinkles, fine lines, rough skin or large-pored skin.
  • FAA and/or its derivatives preferably FAA and/or its derivatives, and especially FAA for the prophylaxis against time- and/or light-induced ageing processes of the human skin or human hair, in particular for prophylaxis against dry skin, wrinkle formation and/or pigment defects, and/or for the reduction or prevention of the harmful effects of UV rays on the skin.
  • compositions containing it preferably appear to have a benefit in tissue regeneration. This is believed to be due to their ability to modulate and preferably stimulate the production of certain advantageous biomolecules, including, but not limited to, collagen I, fibronectin, collagen IV and/or hyaluronic acid, in skin cells.
  • one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA and compositions containing it can preferably be used to improve the visible signs of ageing in human skin, including fine lines, wrinkles, enlarged pores, roughness, dryness, and other skin texture defects such as the stretchmarks (as caused by pregnancy, trauma or other influences) bags under the eyes, also called “puffy eyes” and dark (under eye) circles, both preferably caused by thinning of the skin, insufficient blood circulation and/or slack tissue, especially on repeated topical application.
  • a composition comprising one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA at least once a day for a period of time at least sufficient to provide a reduction of the visible signs of ageing, preferably the visible signs of ageing of the skin and/or hair.
  • the period of time at least sufficient to provide the reduction of the visible signs of ageing generally is between one day and 12 months, preferably three days and six months, more preferably between two weeks and two months.
  • composition comprising one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially
  • the FAA at least once a day for a period of time at least sufficient to provide a reduction of the visible signs of stretch marks.
  • the period of time at least sufficient to provide the reduction of the visible signs of stretch marks generally is between one day and 12 months, preferably three days and six months, more preferably between two weeks and two months.
  • a method and/or a composition for reducing dark circles under the eyes comprising:
  • a composition comprising one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA at least once a day for a period of time at least sufficient to provide a reduction of the dark circles of the portion of human skin.
  • the period of time at least sufficient to provide the reduction of the dark circles generally is between one day and 12 months, preferably three days and six months, more preferably between two weeks and two months.
  • One aspect of the present invention relates to the use of one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA for the protection of the skin against hair treatment agents, especially for the protection of the skin of the head against pigments, dyestuffs, dyes and/or colouring agents which are commonly used for colouring of the hair.
  • FAA for the protection of the skin against hair treatment agents, especially for the protection of the skin of the head against pigments, dyestuffs, dyes and/or colouring agents which are commonly used for colouring of the hair.
  • compositions the contact of the head treatment composition with the underlying skin is normally not completely avoidable.
  • the contact of the head treatment composition with the underlying skin is especially disadvantageous in the case of hair colouring compositions, since the resulting colouration of the parts of the skin around the hair line and/or the roots of the hair is generally regarded as unesthetic and thus undesirous.
  • it is desirous to protect the skin from the negative effects of the hair treatment compositions.
  • the compositions and agents of prior art show only limited efficacy and/or have two be removed after the application of the head treatment composition.
  • vaseline is hard to remove from the skin and/or a hair due to its unsolubility in water.
  • the use of strong detergents and/or organic solvents can become necessary, thereby affecting the intended result of the application of the hair treatment composition and/or having negative effect on the condition of the skin and/or hair.
  • one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA can be advantageously applied to protect the skin against hair treatment agents and especially to protect the skin of the head against adverse effects of pigments, dyestuffs, dyes and/or colouring agents, or hair colouring compositions in general.
  • compositions which can dye, tint, shape, harden, condition, soften, repair or style hair, and especially compositions which can colour or tint the hair.
  • compositions of the invention generally comprise one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA and one or more vehicle or carrier, preferably one or more cosmetically acceptable vehicle or carrier.
  • the one or more vehicles or carriers may be independently selected from the group of hydrophobic and hydrophilic vehicles or carriers.
  • Suitable, hydrophobic vehicles or carriers include, for example, waxy non-ionic substances, preferably waxy non-ionic substances commonly used in cosmetics, including, but not limited to esters and ethers of fatty alcohols and of fatty acids, with carbon chain length from C4 to C22, preferably from C8 to C18, and most preferably from C12 to C18.
  • a fatty hydrophobic carriers or vehicles are preferably selected from the group consisting of isopropyl myristate, isopropyl palmitate, octyl palmitate, isopropyl lanolate, acetylated lanolin alcohol, the benzoate of C12- C15 alcohols, cetearyl octanoate, cetyl palmitate, myristyl myristate, myristyl lactate, cetyl acetate, propylene glycol dicaprylate/caprate, decyl oleate, acetylated lanolin, stearyl heptanoate, diisostearyl malate, octyl
  • hydrophilic carrier or vehicles are preferably selected from the group consisting of glycols and alkoxylated glycols, preferably glycols and alkoxylated glycols commonly used in cosmetics, including, but not limited to, ethylene glycol, diethylene glycol, triethylene glycol, propylene glycol, dipropylene glycol, and the like.
  • compositions according to the invention may be formulated as creams, lotions, serums, sprays, sticks and other forms known to those skilled in the art.
  • Creams and lotions are the currently preferred product forms.
  • the amount typically employed for the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA is from 0.01 to 20% by weight, preferably from 0.1% by weight to 10% by weight and particularly preferably from 1 to 8% by weight.
  • cosmetic compositions can typically comprise the carrier solution described above at levels between about 0.1% and about 90% by weight, preferably between about 1% and about 50%, more preferably between about 1% and about 20%, and more preferred still between about 1% and about 10% by weight.
  • compositions according to the invention may comprise additional active and inactive ingredients other than FAA derivatives, including, but not limited to, excipients, fillers, emulsifying agents,
  • antioxidants surfactants, film formers, chelating agents, gelling agents, thickeners, emollients, humectants, moisturizers, vitamins, minerals, viscosity and/or rheology modifiers, sunscreens, keratolyses, depigmenting agents, retinoids, hormonal compounds, alpha-hydroxy acids, alpha-keto acids, anti- mycobacterial agents, antifungal agents, antimicrobials, antivirals,
  • analgesics lipidic compounds, anti- allergenic agents, H1 and/or or H2 antihistamines, anti-inflammatory agents, anti-irritants, antineoplastics, immune system boosting agents, immune system suppressing agents, antiacne agents, anesthetics, antiseptics, insect repellents, skin cooling compounds, skin protectants, skin penetration enhancers, exfollients, lubricants, fragrances, colorants, staining agents, depigmenting agents, hypopigmenting agents, preservatives, stabilizers, pharmaceutical agents, photostabilizing agents, and mixtures thereof.
  • the personal care products of the invention may contain any other compound for the treatment of skin disorders.
  • the invention also provides a method for ameliorating and/or preventing signs of human skin photo- and intrinsic aging comprising topically applying the cosmetic compositions of the invention.
  • the cosmetic compositions of the invention are preferably applied to affected skin areas once or twice daily for as long as is necessary to achieve desired anti-aging results.
  • the present invention furthermore relates to compositions, preferably non- therapeutic compositions, comprising one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA and at least one further skin-care ingredient and at least one carrier which is suitable for topical applications, and to the use of the above- mentioned compounds for the care, preservation or improvement of the general state of the skin or hair.
  • Uses which are preferred in accordance with the invention are, in particular, the use for prophylaxis against time- and/or light-induced ageing processes of the human skin or human hair, in particular for prophylaxis against dry skin, wrinkle formation and/or pigment defects, and/or for the reduction or prevention of the harmful effects of UV rays on the skin, and for prophylaxis against or reduction of skin unevenness, such as wrinkles, fine lines, rough skin or large-pored skin.
  • Uses which are preferred in accordance with the invention are furthermore the use for the prophylaxis and/or prevention of premature skin ageing, in particular for the prophylaxis and/or prevention of light- or ageing-induced wrinkling of the skin, for the reduction of pigmentation and keratosis actinica, and for the prophylaxis and/or treatment of all diseases which are associated with normal skin ageing or light-induced ageing of the skin, and for the prophylaxis and/or treatment of skin diseases which are associated with defective keratinisation relating to differentiation and cell proliferation, in particular for the treatment of acne vulgaris, acne comedonica, polymorphic acne, acne rosaceae, nodular acne, acne conglobata, age-related acne, acne occuring as a side effect, such as acne Solaris, medicament-related acne or acne professionalis, for the treatment of other defects of
  • keratinisation in particular ichthyosis, ichthyosiform states, Darier's disease, keratosis palmoplantaris, leukoplakia, leukoplakiform states, skin and mucosal (buccal) eczema (lichen), for the treatment of other skin diseases which are associated with defective keratinisation and have an inflammatory and/or immunoallergic component, and in particular all forms of psoriasis relating to the skin, mucous membranes and finger- and toenails, and psoriatic rheumatism and skin atopy, such as eczema, or respiratory atopy, or also hypertrophy of the gums, and for the prophylaxis and/or treatment of all benign or malignant excrescence of the dermis or epidermis, which may be of viral origin, such as verruca vulgaris, verruca plana, epidermodysplasia verruciformis, oral
  • the present invention also relates to the use of one or more of the
  • compositions here are preferably non-therapeutical, more preferably either compositions which can be used topically, for example cosmetic or dermatological formulations.
  • the compositions comprise a cosmetically or dermatologically carrier and, depending on the desired property profile, optionally further suitable ingredients.
  • the present invention furthermore relates to the use of the above-mentioned compositions for the prevention of undesired changes in the skin picture, such as, for example, acne or greasy skin, keratoses, light-sensitive, inflammatory, erythematous, allergic or autoimmune-reactive reactions.
  • one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA and compositions according to the invention preferably also serve for calming sensitive and irritated skin, for the preventative regulation of collagen, hyaluronic acid and elastin synthesis, stimulation of DNA synthesis, in particular in the case of deficient or hypoactive skin states, regulation of the transcription and translation of matrix-degrading enzymes, in particular of MMPs, increasing cell
  • One or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA are typically employed in
  • At least one further skin- care ingredient is one or more antioxidants and/or vitamins.
  • antioxidants for example amino acids (for example glycine, histidine, tyrosine, tryptophan) and derivatives thereof, imidazoles (for example urocanic acid) and derivatives thereof, peptides, such as D, L- camosine, D-camosine, L-camosine and derivatives thereof (for example anserine), carotinoids, carotenes (for example ⁇ -carotene, ⁇ -carotene, lycopene) and derivatives thereof, chlorogenic acid and derivatives thereof, lipoic acid and derivatives thereof (for example dihydrolipoic acid),
  • amino acids for example glycine, histidine, tyrosine, tryptophan
  • imidazoles for example urocanic acid
  • peptides such as D, L- camosine, D-camosine, L-camosine and derivatives thereof (for example anserine)
  • carotinoids for example ⁇ -carotene, ⁇ -car
  • aurothioglucose propylthiouracil and other thiols (for example thioredoxin, glutathione, cysteine, cystine, cystamine and the glycosyl, N-acetyl, methyl, ethyl, propyl, amyl, butyl and lauryl, palmitoyl, oleyl, ⁇ -linoleyl, cholesteryl and glyceryl esters thereof) and salts thereof, dilauryl thiodipropionate, distearyl thiodipropionate, thiodipropionic acid and derivatives thereof (esters, ethers, peptides, lipids, nucleotides, nucleosides and salts), and sulfoximine compounds (for example buthionine sulfoximines, homocysteine sulfoximine, buthionine sulfones, penta-, hexa-
  • stilbenes and derivatives thereof (for example stilbene oxide, trans-stilbene oxide).
  • Suitable antioxidants are furthermore described in WO 2006/111233 and WO 2006/111234.
  • Suitable antioxidants are also compounds of the general formula A and/or B
  • R 1 is selected from the group consisting of -C(O)CH 3 , -CO 2 R 3 , -C(O)NH 2 and
  • X is O or NH
  • R 2 is linear or branched Alkyl having 1 to 30 C-atoms
  • R 3 is linear or branched Alkyl having 1 to 20 C-atoms
  • R 4 is in each case independently selected from the group consisting of H and linear or branched Alkyl having 1 to 8 C-atoms,
  • R 5 is selected from the group consisting of linear or branched Alkyl having 1 to 8 C-atoms and linear or branched Alkoxy having 1 to 8 C-atoms and
  • R 6 is selected from the group consisting of linear or branched Alkyl mit 1 to 8
  • C-atoms preferably selected from derivatives of the 2-(4-Hydroxy- 3,5-dimethoxybenzyliden)-malonic acid and/or 2-(4-Hydroxy-3,5- dimethoxybenzyl)-malonic acid , and especially preferably selected from 2-(4- Hydroxy-3,5-dimethoxybenzyliden)-malonic acid-bis-(2-ethylhexyl)ester (z.B. Oxynex ® ST Liquid) and/or 2-(4-Hydroxy-3,5-dimethoxybenzyl)-malonic acid- bis-(2-ethylhexyl)ester (z.B. RonaCare ® AP).
  • antioxidants are likewise suitable for use in the cosmetic compositions according to the invention.
  • Known and commercial mixtures are, for example, mixtures comprising, as active ingredients, lecithin, L-(+)-ascorbyl palmitate and citric acid (for example Oxynex ® AP), natural tocopherols, L-(+)-ascorbyl palmitate, L-(+)-ascorbic acid and citric acid (for example
  • Oxynex ® K LIQUID tocopherol extracts from natural sources, L-(+)-ascorbyl palmitate, L-(+)-ascorbic acid and citric acid (for example Oxynex ® L
  • Antioxidants of this type are usually employed with one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA in compositions of this type in ratios in the range from 1000:1 to 1 :1000, preferably in amounts of from 100:1 to 1:100.
  • compositions according to the invention may comprise vitamins as further ingredients.
  • the cosmetic compositions according to the invention preferably comprise vitamins and vitamin derivatives selected from vitamin B, thiamine chloride hydrochloride (vitamin B-i), riboflavin (vitamin B 2 ), nicotinamide, vitamin C (ascorbic acid), vitamin D, ergocalciferol (vitamin D 2 ), vitamin E, DL- ⁇ -tocopherol, tocopherol E acetate, tocopherol
  • Vitamins are usually employed here with FAA derivatives, in ratios in the range from 1000:1 to 1 :1000, preferably in amounts of from 100:1 to 1:100.
  • the polyphenols are of particular interest for applications in the pharmaceutical, cosmetic or nutrition sector.
  • the flavonoids or bioflavonoids which are principally known as plant dyes, frequently have an antioxidant potential.
  • Quercetin (cyanidanol, cyanidenolon 1522, meletin, sophoretin, ericin, 3,3',4',5,7-pentahydroxyflavone) is frequently mentioned as a particularly effective antioxidant (for example CA. Rice-Evans, N.J. Miller, G. Paganga, Trends in Plant Science 1997, 2(4), 152-159).
  • K. Lemanska, H. Szymusiak, B. Tyrakowska, R. Zielinski, A.E.M.F. Soffers, I. M. C. M. Rietjens; Free Radical Biology&Medicine 2001 , 31(7), 869-881 have investigated the pH dependence of the antioxidant action of hydroxyflavones. Quercetin exhibits the greatest activity amongst the structures investigated over the entire pH range.
  • Suitable antioxidants are furthermore compounds of the formula C
  • R 1 to R 10 may be identical or different and are selected from
  • hydroxyl group may be bonded to a primary or secondary carbon atom of the chain and furthermore the alkyl chain may also be interrupted by oxygen and/or
  • hydroxyl group(s) may be bonded to a primary or secondary carbon atom of the chain and furthermore the alkyl chain may also be interrupted by oxygen, and/or
  • compositions according to the invention comprising at least one antioxidant here are, in particular, the antioxidant action and the good skin tolerability.
  • the compounds of formula C are preferably colourless or have only a weak colour and thus only result in slight discoloration of the compositions, or none at all. It may be also advantageous to administer the compounds of the formula C in encapsulated form, for example as cellulose or chitin capsules, in gelatine or wax matrices or encapsulated with cyclodextrins.
  • compositions according to the invention are also suitable for the treatment of skin diseases associated with a defect in keratinisation which affects differentiation and cell proliferation, in particular for the treatment of acne vulgaris, acne comedonica, polymorphic acne, acne rosaceae, nodular acne, acne conglobata, age-induced acne, acne which arises as a side effect, such as acne Solaris, medicament-induced acne or acne professionalis, for the treatment of other defects in keratinisation, in particular ichthyosis, ichthyosiform states, Darier's disease, keratosis palmoplantaris, leucoplasia, leucoplasiform states, herpes of the skin and mucous membrane (buccal) (lichen), for the treatment of other skin diseases associated with a defect in keratinisation and which have an inflammatory and/or immunoallergic component and in particular all forms of psoriasis which affect the skin, mucous membranes and fingers and toenails, and ps
  • spinocellulare for the treatment of other skin diseases, such as dermatitis bullosa and diseases affecting the collagen, for the treatment of certain eye diseases, in particular corneal diseases, for overcoming or combating light- induced skin ageing associated with ageing, for reducing pigmentation and keratosis actinica and for the treatment of all diseases associated with normal ageing or light-induced ageing, for the prevention or healing of wounds/scars of atrophy of the epidermis and/or dermis caused by locally or systemically applied corticosteroids and all other types of skin atrophy, for the prevention or treatment of defects in wound healing, for the prevention or elimination of stretch marks caused by pregnancy or for the promotion of wound healing, for combating defects in tallow production, such as hyperseborrhoea in acne or simple seborrhoea, for combating or preventing cancer-like states or pre-carcinogenic states, in particular promyelocytic leukaemia, for the treatment of inflammatory diseases, such as arthritis, for the treatment of all
  • arteriosclerosis or hypertension and of non-insulin-dependent diabetes, and for the treatment of skin problems caused by UV radiation.
  • compositions which are particularly preferred in accordance with the invention also comprise organic hydrophilic or lipophilic sun-protection filter(s) (UV filters) besides one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, or especially FAA.
  • UV filters organic hydrophilic or lipophilic sun-protection filter(s)
  • UV filters are effective in the UV-A region and/or UV-B region and/or IR and/or VIS region (absorbers).
  • additional filters can be selected, in particular, from cinnamic acid derivatives, salicylic acid derivatives, camphor derivatives, triazine derivatives, ⁇ , ⁇ -diphenylacrylate derivatives, p-aminobenzoic acid derivatives and polymeric filters and silicone filters, which are described in the application WO 93/04665. Further examples of organic filters are indicated in the patent application EP-A 0 487 404.
  • the said UV filters are usually named below in accordance with INCI nomenclature.
  • para-aminobenzoic acid and derivatives thereof PABA, Ethyl PABA, Ethyl dihydroxypropyl PABA, Ethylhexyl dimethyl PABA, for example marketed under the name “Escalol 507" by ISP, Glyceryl PABA, PEG- 25 PABA, for example marketed under the name "Uvinul P25" by
  • Salicylates homosalate marketed under the name "Eusolex HMS” by Merck; ethylhexyl salicylate, for example marketed under the name “Neo Heliopan OS” by Haarmann and Reirner, dipropylene glycol salicylate, for example marketed under the name “Dipsal” by Scher, TEA salicylate, for example marketed under the name “Neo Heliopan TS” by Haarmann and Reimer.
  • ⁇ , ⁇ -Diphenylacrylate derivatives octocrylene, for example marketed under 10 the name "Uvinul N539" by BASF, etocrylene, for example marketed under the name "Uvinul N35” by BASF.
  • Benzophenone derivatives benzophenone-1 , for example marketed under the name "Uvinul 400"; benzophenone-2, for example marketed under the name “Uvinul D50”; benzophenone-3 or oxybenzone, for example marketed 15 under the name “Uvinul M40”; benzophenone-4, for example marketed under the name “Uvinul MS40”; benzophenone-9, for example marketed under the name "Uvinul DS-49" by BASF, benzophenone-5, benzophenone-6, for example marketed under the name "Helisorb 11" by Norquay,
  • benzophenone-8 for example marketed under the name "Spectra-Sorb UV-
  • Benzylidenecamphor derivatives 3-benzylidenecamphor, for example marketed under the name “Mexoryl SD” by Chimex, 4-methylbenzylidene- camphor, for example marketed under the name “Eusolex 6300” by Merck, p j .
  • benzylidenecamphorsulfonic acid for example marketed under the name
  • “Mexoryl SL” by Chimex camphor benzalkonium methosulfate, for example marketed under the name “Mexoryl SO” by Chimex, terephthalylidene- dicamphorsulfonic acid, for example marketed under the name “Mexoryl SX” by Chimex, polyacrylamidomethylbenzylidenecamphor marketed under the name “Mexoryl SW” by Chimex.
  • Phenylbenzimidazole derivatives phenylbenzimidazolesulfonic acid, for example marketed under the name “Eusolex 232" by Merck, disodium phenyl dibenzimidazole tetrasulfonate, for example marketed under the name “Neo Heliopan AP” by Haarmann and Reimer.
  • Phenylbenzotriazole derivatives drometrizole trisiloxane, for example mar- keted under the name “Silatrizole” by Rhodia Chimie, methylenebis(benzo- triazolyl)tetramethylbutylphenol in solid form, for example marketed under the name "MIXXIM BB/100” by Fairmount Chemical, or in micronised form as an aqueous dispersion, for example marketed under the name "Tinosorb M” by Ciba Specialty Chemicals.
  • Triazine derivatives ethylhexyltriazone, for example marketed under the name “Uvinul T150” by BASF, diethylhexylbutamidotriazone, for example marketed under the name “Uvasorb HEB” by Sigma 3V, 2,4,6-tris(diisobutyl- 4'-aminobenzalmalonate)-s-triazine.
  • Anthraniline derivatives menthyl anthranilate, for example marketed under the name "Neo Heliopan MA” by Haarmann and Reimer.
  • Imidazole derivatives ethylhexyldimethoxybenzylidenedioxoimidazoline propionate.
  • Benzalmalonate derivatives polyorganosiloxanes containing functional benzalmalonate groups, such as, for example, polysilicone-15, for example marketed under the name "Parsol SLX” by Hoffmann LaRoche.
  • 4,4-Diarylbutadiene derivatives 1 ,1-dicarboxy(2,2'-dimethylpropyl)-4,4- diphenylbutadiene.
  • Benzoxazole derivatives 2,4-bis[5-(1-dimethylpropyl)benzoxazol-2-yl(4- phenyl)imino]-6-(2-ethylhexyl)imino-1 ,3,5-triazine, for example marketed under the name Uvasorb K2A by Sigma 3V, and mixtures comprising this.
  • the organic UV-protecting substances which are suitable for combination with the UV protection agent according to the invention can preferably be selected from the following list: Ethylhexyl salicylate, Octocrylene, Butyl- methoxydibenzoylmethane, Phenylbenzimidazolesulfonic acid, Benzo- phenone-3, Benzophenone-4, Benzophenone-5, n-Hexyl 2-(4-diethylamino- 2-hydroxybenzoyl)benzoate, 4-Methylbenzylidenecamphor, Terephthalyli- denedicamphorsulfonic acid, Disodium phenyldibenzimidazoletetrasulfonate, Methylenebis(benzotriazolyl)tetramethylbutylphenol, Ethylhexyl Triazone, Diethylhexyl Butamido Triazone, Drometrizole trisiloxane, Polysilicone-15, 1 ,
  • organic UV filters are generally incorporated into cosmetic formulations in an amount of 0.01 to 20 per cent by weight, preferably 1-10% by weight.
  • Organic UV filters are generally incorporated into cosmetic formulations in a total amount of 0.01 to 20 per cent by weight, preferably 0.5-20%.
  • Compositions which are particularly preferred in accordance with the invention may also comprise inorganic sun-protection filter(s) (particulate UV filters) besides one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, or especially FAA.
  • Particulate UV filters may be comprised both as powder and also as dispersion or paste. Preference is given here both to those from the group of the titanium dioxides, such as, for example, coated titanium dioxide (for example
  • compositions may furthermore be preferred in accordance with the invention for the compositions to comprise inorganic UV filters which have been aftertreated by conventional methods, as described, for example, in Cosmetics &
  • One or more of the following aftertreatment components can be selected here: amino acids, beeswax, fatty acids, fatty acid alcohols, anionic surfactants, lecithin, phospholipids, sodium, potassium, zinc, iron or aluminium salts of fatty acids, polyethylenes, silicones, proteins (particularly collagen or elastin), alkanolamines, silicon dioxide, aluminium oxide, further metal oxides, phosphates, such as sodium hexametaphosphate, or glycerin.
  • Further particulate UV filters which are preferably employed here are: - untreated titanium dioxides, such as, for example, the products Micro- titanium Dioxide MT 500 B from Tayca; titanium dioxide P25 from Degussa, aftertreated micronised titanium dioxides with aluminium oxide and silicon dioxide aftertreatment, such as, for example, the product "Microtitanium Dioxide MT 100 SA" from Tayca; or the product "Tioveil Fin” from Uniqema,
  • micronised titanium dioxides with aluminium oxide and/or aluminium stearate/laurate aftertreatment such as, for example, Microtitanium Dioxide MT 100 T from Tayca, Eusolex T-2000 from Merck,
  • micronised titanium dioxides with iron oxide and/or iron stearate aftertreatment such as, for example, the product "Microtitanium Dioxide MT 100 F" from Tayca,
  • micronised titanium dioxides with silicon dioxide, aluminium oxide and silicone aftertreatment, such as, for example, the product "Microtitanium Dioxide MT 100 SAS" from Tayca,
  • micronised titanium dioxides with sodium hexametaphos- phates such as, for example, the product "Microtitanium Dioxide MT 150 W" from Tayca.
  • the treated micronised titanium dioxides employed for the combination may also be aftertreated with:
  • octyltrimethoxysilanes such as, for example, the product Tego Sun T
  • silicon dioxide such as, for example, the product Parsol T-X from DSM, aluminium oxide and stearic acid; such as, for example, the product UV- ?J - Titan M160 from Kemira,
  • aluminium and glycerin such as, for example, the product UV-Titan from Kemira,
  • silicone oils such as, for example, the product UV-Titan M262 from Kemira,
  • polydimethylsiloxanes such as, for example, the product 70250 Cardre UF TiO2SI3 from Cardre, polydimethylhydrogenosiloxanes, such as, for example, the product Microtitanium Dioxide USP Grade Hydrophobic from Color Techniques.
  • untreated zinc oxides such as, for example, the product Z-Cote from BASF (Sunsmart), Nanox from Elementis
  • Escalol Z100 from ISP (aluminium oxide-aftertreated ZnO dispersed in an ethylhexyl methoxycinnamate/PVP-hexadecene/- methicone copolymer mixture)
  • o untreated and/or aftertreated iron oxides with the name Nanogar from Arnaud.
  • various metal oxides such as, for example, titanium dioxide and cerium oxide
  • aftertreatment such as, for example, the product Sunveil A from Ikeda
  • mixtures of aluminium oxide, silicon dioxide and silicone-aftertreated titanium dioxide, zinc oxide mixtures such as, for example, the product UV-Titan M261 from Kemira, in combination with the UV protection agent according to the invention.
  • inorganic UV filters are generally incorporated into cosmetic compositions in an amount of 0.1 to 25 per cent by weight, preferably 2-10%.
  • a nanoparticulate UV protection agent according to the invention may be present in one phase in emulsions and a further inorganic UV filter to be present in the other phase.
  • (I) preferably FAA and/or its derivatives, and especially FAA with further UV filters, the protective action against harmful influences of UV radiation can be optimised.
  • UV filters can also be employed in encapsulated form.
  • organic UV filters in encapsulated form.
  • the hydrophilicity of the capsule wall can be set independently of the solubility of the UV filter.
  • hydrophobic UV filters into purely aqueous compositions.
  • Certain UV filters in particular dibenzoylmethane derivatives, exhibit only reduced photostability in cosmetic compositions. Encapsulation of these filters or compounds which impair the photostability of these filters, such as, for example, cinnamic acid derivatives, enables the photostability of the entire composition to be increased.
  • encapsulation of individual UV filters or other ingredients enables composition problems caused by the interaction of individual composition constituents with one another, such as crystallisation processes, precipitation and agglomerate formation, to be avoided since the interaction is suppressed.
  • one or more of the above-mentioned UV filters prefferably be in encapsulated form. It is advantageous here for the capsules to be so small that they cannot be viewed with the naked eye. In order to achieve the above-mentioned effects, it is furthermore necessary for the capsules to be sufficiently stable and the encapsulated active ingredient (UV filter) only to be released to the environ- ment to a small extent, or not at all.
  • Suitable capsules can have walls of inorganic or organic polymers.
  • US 6,242,099 B1 describes the production of suitable capsules with walls of chitin, chitin derivatives or polyhydroxylated polyamines.
  • Capsules which can particularly preferably be employed in accordance with the invention have walls which can be obtained by a sol-gel process, as described in the applications WO 00/09652, WO 00/72806 and
  • the capsules are preferably present in compositions according to the invention in amounts which ensure that the encapsulated UV filters are present in the composition in the above-indicated amounts.
  • the skin-protecting or skin-care active ingredients can in principle be any active ingredients known to the person skilled in the art.
  • particularly preferred active ingredients are pyrimidinecarboxylic acids and/or aryl oximes.
  • Pyrimidinecarboxylic acids occur in halophilic microorganisms and play a role in osmoregulation of these organisms (E.A. Galinski et al., Eur. J. Biochem., 149 (1985) pages 135-139).
  • pyrimidinecarboxylic acids particular mention should be made here of ectoine ((S)-1 ,4,5,6-tetrahydro-2-methyl-4- pyrimidinecarboxylic acid) and hydroxyectoine ((S 1 S)-1 ,4,5,6-tetrahydro-5- hydroxy-2-methyl-4-pyrimidinecarboxylic acid) and derivatives thereof.
  • These compounds stabilise enzymes and other biomolecules in aqueous solutions and organic solvents. Furthermore, they stabilise, in particular, enzymes against denaturing conditions, such as salts, extreme pH values, surfactants, urea, guanidinium chloride and other compounds.
  • Ectoine and ectoine derivatives such as hydroxyectoine
  • hydroxyectoine can be employed for the preparation of a medicament for the treatment of skin diseases.
  • European patent application EP-A-O 671 161 describes, in particular, that ectoine and hydroxyectoine are employed in cosmetic compositions, such as powders, soaps, surfactant-containing cleansing products, lipsticks, rouge, make-ups, care creams and sunscreen compositions.
  • R 1 is a radical H or C1-8-alkyl
  • R 2 is a radical H or C1-4-alkyl
  • R 2 is a methyl or ethyl group, and R 1 or R 5 and R 6 are H.
  • compositions according to the invention preferably comprise pyrimidinecarboxylic acids of this type in amounts of up to 15% by weight.
  • the pyrimidinecarboxylic acids are preferably employed here in ratios of from 100:1 to 1 :100 with respect to one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA with ratios in the range from 1 :10 to 10:1 being particularly preferred.
  • 2-hydroxy-5-methyllauro- phenone oxime which is also known as HMLO, LPO or F5. Its suitability for use in cosmetic compositions is disclosed, for example, in DE-A-41 16 123.
  • Compositions which comprise 2-hydroxy-5-methyllaurophenone oxime are accordingly suitable for the treatment of skin diseases which are
  • compositions of this type can be used, for example, for the therapy of psoriasis, various forms of eczema, irritative and toxic dermatitis, UV dermatitis and further allergic and/or inflammatory diseases of the skin and integumentary appendages.
  • compositions according to the invention which, in addition to one or more of the compounds according to formula (I), preferably FAA and/or its
  • compositions here preferably comprise from 0.01 to 10% by weight of the aryl oxime, it being particularly preferred for the composition to comprise from 0.05 to 5% by weight of aryl oxime.
  • All compounds or components which can be used in the compositions are either known or commercially available or can be synthesised by known processes.
  • the preparation of one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA is described in one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA can be incorporated into cosmetic or dermatological compositions in the customary manner. Suitable
  • compositions are for example in the form of a cream, lotion or gel or as a solution which can be sprayed onto the skin.
  • Use forms of the compositions according to the invention that may be mentioned are, for example, solutions, suspensions, emulsions, PIT emulsions, pastes, ointments, gels, creams, lotions, powders, soaps, surfactant-containing cleansing preparations, oils, aerosols and sprays.
  • Examples of other use forms are sticks, shampoos and shower compositions.
  • any desired customary carriers, assistants and, if desired, further active ingredients may be added to the composition.
  • Preferred assistants originate from the group consisting of preservatives, antioxidants, stabilisers, solubilisers, vitamins, colorants and odour im- provers.
  • Ointments, pastes, creams and gels may comprise the customary carriers, for example animal and vegetable fats, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silica, talc and zinc oxide, or mixtures of these substances.
  • customary carriers for example 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 may comprise the customary carriers, for example lactose, talc, silica, aluminium hydroxide, calcium silicate and polyamide powder, or mixtures of these substances.
  • Sprays may additionally comprise the customary propellants, for example chlorofluorocarbons, propane/butane or dimethyl ether.
  • Solutions and emulsions may comprise the customary carriers, such as solvents, solubilisers and emulsifiers, for example water, ethanol,
  • Suspensions may comprise the customary carriers, such as liquid diluents, for example water, ethanol or propylene glycol, suspending agents, for example ethoxylated isostearyl alcohols, polyoxyethylene sorbitol esters and polyoxyethylene sorbitan esters, microcrystalline cellulose, aluminium metahydroxide, bentonite, agar-agar and tragacanth, or mixtures of these substances.
  • liquid diluents for example water, ethanol or propylene glycol
  • suspending agents for example ethoxylated isostearyl alcohols, polyoxyethylene sorbitol esters and polyoxyethylene sorbitan esters, microcrystalline cellulose, aluminium metahydroxide, bentonite, agar-agar and tragacanth, or mixtures of these substances.
  • Soaps may comprise the customary carriers, such as alkali metal salts of fatty acids, salts of fatty acid monoesters, fatty acid protein hydrolysates, isethionates, lanolin, fatty alcohol, vegetable oils, plant extracts, glycerol, sugars, or mixtures of these substances.
  • customary carriers such as alkali metal salts of fatty acids, salts of fatty acid monoesters, fatty acid protein hydrolysates, isethionates, lanolin, fatty alcohol, vegetable oils, plant extracts, glycerol, sugars, or mixtures of these substances.
  • Surfactant-containing cleansing products may comprise the customary carriers, such as salts of fatty alcohol sulfates, fatty alcohol ether sulfates, sulfosuccinic acid monoesters, fatty acid protein hydrolysates, isothionates, imidazolinium derivatives, methyl taurates, sarcosinates, fatty acid amide ether sulfates, alkylamidobetaines, fatty alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable and synthetic oils, lanolin derivatives, ethoxylated glycerol fatty acid esters, or mixtures of these substances.
  • customary carriers such as salts of fatty alcohol sulfates, fatty alcohol ether sulfates, sulfosuccinic acid monoesters, fatty acid protein hydrolysates, isothionates, imidazolinium derivatives, methyl taurates, sarcosinates, fatty
  • Face and body oils may comprise the customary carriers, such as synthetic oils, such as fatty acid esters, fatty alcohols, silicone oils, natural oils, such as vegetable oils and oily plant extracts, paraffin oils or lanolin oils, or mixtures of these substances.
  • synthetic oils such as fatty acid esters, fatty alcohols, silicone oils, natural oils, such as vegetable oils and oily plant extracts, paraffin oils or lanolin oils, or mixtures of these substances.
  • composition forms according to the invention include, in par- ticular, emulsions.
  • Emulsions according to the invention are advantageous and comprise, for example, the fats, oils, waxes and other fatty substances, as well as water and an emulsifier, as usually used for a composition of this type.
  • oils such as triglycerides of capric or caprylic acid, furthermore natural oils, such as, for example, castor oil;
  • esters of fatty acids with alcohols having a low carbon number for example with isopropanol, propylene glycol or glycerol, or esters of fatty alcohols with alkanoic acids having a low carbon number or with fatty acids; - silicone oils, such as dimethylpolysiloxanes, diethylpolysiloxanes, diphenylpolysiloxanes and mixed forms thereof.
  • the oil phase of the emulsions, oleogels or hydrodispersions or lipodispersions is advantageously selected from the group consisting of esters of saturated and/or unsaturated, branched and/or unbranched alkanecarboxylic acids having a chain length of from 3 to 30 carbon atoms and saturated and/or unsaturated, branched and/or unbranched alcohols having a chain length of from 3 to 30 carbon atoms, or from the group consisting of esters of aromatic carboxylic acids and saturated and/or unsaturated, branched and/or unbranched alcohols having a chain length of from 3 to 30 carbon atoms.
  • Ester oils of this type can then advantageously be selected from the group consisting of isopropyl myristate, isopropyl palmitate, isopropyl stearate, isopropyl oleate, n-butyl stearate, n-hexyl laurate, n-decyl oleate, isooctyl stearate, isononyl stearate, isononyl isononanoate, 2-ethylhexyl palmitate, 2-ethylhexyl laurate,
  • the oil phase may furthermore advantageously be selected from the group consisting of branched and unbranched hydrocarbons and waxes, silicone oils, dialkyl ethers, or the group consisting of saturated and unsaturated, branched and unbranched alcohols, and fatty acid triglycerides, specifically the triglycerol esters of saturated and/or unsaturated, branched and/or unbranched alkanecarboxylic acids having a chain length of from 8 to 24, in particular 12-18, carbon atoms.
  • the fatty acid triglycerides may be selected from the group consisting of branched and unbranched hydrocarbons and waxes, silicone oils, dialkyl ethers, or the group consisting of saturated and unsaturated, branched and unbranched alcohols, and fatty acid triglycerides, specifically the triglycerol esters of saturated and/or unsaturated, branched and/or unbranched alkanecarboxylic acids having a chain length of from 8 to
  • oils for example olive oil, sunflower oil, soya oil, peanut oil, rapeseed oil, almond oil, palm oil, coconut oil, palm kernel oil and the like.
  • any desired mixtures of oil and wax components of this type may also advantageously be employed for the purposes of the present invention. It may also be advantageous to employ waxes, for example cetyl palmitate, as the only lipid component of the oil phase.
  • the oil phase is advantageously selected from the group consisting of 2-ethylhexyl isostearate, octyldodecanol, isotridecyl isononanoate, iso- eicosane, 2-ethylhexyl cocoate, benzoate, caprylic/capric acid triglyceride and dicapryl ether.
  • Ci 2 -is-alkyl benzoate and 2- ethylhexyl isostearate mixtures of Ci 2 -i 5 -alkyl benzoate and isotridecyl isononanoate, as well as mixtures of Ci 2- i 5 -alkyl benzoate, 2-ethylhexyl isostearate and isotridecyl isononanoate.
  • paraffin oil squalane and squalene
  • oil phase may also advantageously have a content of cyclic or linear silicone oils or consist entirely of oils of this type, although it is preferred to use an additional content of other oil-phase components in addition to the silicone oil or the silicone oils.
  • the silicone oil to be used in accordance with the invention is advantageously cyclomethicone (octamethylcyclotetrasiloxane). However, it is also advantageous for the purposes of the present invention to use other silicone oils, for example hexamethylcyclotrisiloxane, polydimethylsiloxane or poly(methylphenylsiloxane).
  • the aqueous phase of the compositions according to the invention optionally advantageously comprises alcohols, diols or polyols having a low carbon number, and ethers thereof, preferably ethanol, isopropanol, propylene glycol, glycerol, ethylene glycol, ethylene glycol monoethyl or monobutyl ether, propylene glycol monomethyl, monoethyl or monobutyl ether, diethylene glycol monomethyl or monoethyl ether and analogous products, furthermore alcohols having a low carbon number, for example ethanol, isopropanol, 1 ,2-propanediol or glycerol, and, in particular, one or more thickeners, which may advantageously be selected from the group consisting of silicon dioxide, aluminium silicates, poly
  • hydroxypropylmethylcellulose particularly advantageously from the group consisting of the polyacrylates, preferably a polyacrylate from the group consisting of the so-called Carbopols, for example Carbopol grades 980, 981 ,
  • mixtures of the above-mentioned solvents are used.
  • water may be a further constituent.
  • compositions according to the invention comprise hydrophilic surfactants.
  • hydrophilic surfactants are preferably selected from the group consisting of the alkylglucosides, acyllactylates, betaines and coconut amphoacetates.
  • glucopyranoside nonyl glucopyranoside, decyl glucopyranoside, undecyl glucopyranoside, dodecyl glucopyranoside, tetradecyl glucopyranoside and hexadecyl glucopyranoside.
  • Plantaren ® 1200 (Henkel KGaA), Oramix ® NS 10 (Seppic).
  • sodium isostearyl lactylate for example the product Pathionic ®
  • R 2 is a branched or unbranched alkyl radical having from 1 to 30 carbon atoms.
  • R 2 is particularly advantageously a branched or unbranched alkyl radical having from 6 to 12 carbon atoms.
  • capramidopropylbetaine for example the product Tego ® Betain 810 from Th. Goldschmidt AG 1 is advantageous.
  • a coconut amphoacetate which is advantageous for the purposes of the invention is, for example, sodium coconut amphoacetate, as available under the name Miranol ® Ultra C32 from Miranol Chemical Corp.
  • hydrophilic surfactant(s) is (are) present in concentrations of 0.01-20% by weight, preferably 0.05-10% by weight, particularly preferably 0.1-5% by weight, in each case based on the total weight of the composition.
  • Cosmetic and dermatological compositions are applied in sufficient amount to the skin and/or hair in the usual manner for cosmetics.
  • Cosmetic and dermatological compositions according to the invention may exist in various forms. Thus, they may be, for example, a solution, a water- free composition, an emulsion or microemulsion of the water-in-oil (W/O) or oil-in-water (O/W) type, a multiple emulsion, for example of the water-in-oil- in-water (W/O/W) type, a gel, a solid stick, an ointment or an aerosol.
  • ectoines in encapsulated form, for example in collagen matrices and other conventional encapsulation materials, for example as cellulose encapsulations, in gelatine, wax matrices or liposomally encapsulated.
  • wax matrices as described in DE-A 43 08 282, have proven favourable.
  • Emulsifiers that can be used are, for example, the known W/O and O/W emulsifiers. It is advantageous to use further conventional co-emulsifiers in the preferred O/W emulsions according to the invention.
  • Co-emulsifiers which are advantageous according to the invention are, for example, O/W emulsifiers, principally from the group consisting of the substances having HLB values of 11-16, very particularly advantageously having HLB values of 14.5-15.5, so long as the O/W emulsifiers have saturated radicals R and R'. If the O/W emulsifiers have unsaturated radicals R and/or
  • the preferred HLB value of such emulsifiers may also be lower or higher.
  • fatty alcohol ethoxylates from the group consisting of ethoxylated stearyl alcohols, cetyl alcohols, cetylstearyl alcohols (cetearyl alcohols). Particular preference is given to the following:
  • polyethylene glycol glycerol fatty acid esters from the group consisting of polyethylene glycol (20) glyceryl laurate, polyethylene glycol (21) glyceryl laurate, polyethylene glycol (22) glyceryl laurate, polyethylene glycol (23) glyceryl laurate, polyethylene glycol (6) glyceryl caprate/caprinate, polyethylene glycol (20) glyceryl oleate, polyethylene glycol (20) glyceryl isostearate, polyethylene glycol (18) glyceryl oleate/cocoate.
  • polyethylene glycol (20) glyceryl laurate polyethylene glycol (21) glyceryl laurate
  • polyethylene glycol (22) glyceryl laurate polyethylene glycol (23) glyceryl laurate
  • polyethylene glycol (6) glyceryl caprate/caprinate polyethylene glycol (20) glyceryl oleate
  • polyethylene glycol (20) sorbitan monolaurate consisting of polyethylene glycol (20) sorbitan monolaurate, polyethylene glycol (20) sorbitan monostearate, polyethylene glycol (20) sorbitan
  • fatty alcohols having from 8 to 30 carbon atoms monoglycerol esters of saturated and/or unsaturated, branched and/or unbranched alkanecarboxylic acids having a chain length of from 8 to 24 carbon atoms, in particular 12-18 carbon atoms, diglycerol esters of saturated and/or unsaturated, branched and/or unbranched alkanecarboxylic acids having a chain length of from 8 to 24 carbon atoms, in particular 12-18 carbon atoms, monoglycerol ethers of saturated and/or unsaturated, branched and/or unbranched alcohols having a chain length of from 8 to 24 carbon atoms, in particular 12-18 carbon atoms, diglycerol ethers of saturated and/or unsaturated, branched and/or unbranched alcohols having a chain length of from 8 to 24 carbon atoms, in particular 12-18 carbon atoms, propylene glycol esters of saturated and/or unsaturated, branched and/or unbranched
  • W/O emulsifiers are glyceryl monostearate, glyceryl monoisostearate, glyceryl monomyristate, glyceryl monooleate, diglyceryl monostearate, diglyceryl monoisostearate, propylene glycol monostearate, propylene glycol monoisostearate, propylene glycol monocaprylate, propylene glycol monolaurate, sorbitan monoisostearate, sorbitan monolaurate, sorbitan monocaprylate, sorbitan monoisooleate, sucrose distearate, cetyl alcohol, stearyl alcohol, arachidyl alcohol, behenyl alcohol, isobehenyl alcohol, selachyl alcohol, chimyl alcohol, polyethylene glycol (2) stearyl ether (steareth-2), glyceryl monolaurate, glyceryl mono- caprinate and glyceryl monocaprylate.
  • compositions according to the invention are particularly suitable for protecting human skin against ageing processes and against oxidative stress, i.e. against damage by free radicals, as are produced, for example, by sunlight, heat or other influences.
  • they are in the various administration forms usually used for this application.
  • they may, in particular, be in the form of a lotion or emulsion, such as in the form of a cream or milk (O/W, W/O, O ⁇ /V/0, W/O ⁇ /V), in the form of oily-alcoholic, oily- aqueous or aqueous-alcoholic gels or solutions, in the form of solid sticks or may be formulated as an aerosol.
  • composition may comprise cosmetic adjuvants which are usually used in this type of composition, such as, for example, thickeners, softeners, moisturisers, surfactants, emulsifiers, preservatives, antifoams, perfumes, waxes, lanolin, propellants, dyes and/or pigments which colour the
  • composition itself or the skin, and other ingredients usually used in
  • the dispersant or solubiliser used can be an oil, wax or other fatty substance, a lower monoalcohol or lower polyol or mixtures thereof.
  • Particularly preferred monoalcohols or polyols include ethanol, isopropanol, propylene glycol, glycerol and sorbitol.
  • a preferred embodiment of the invention is an emulsion in the form of a protective cream or milk which, apart from one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA comprises, for example, fatty alcohols, fatty acids, fatty acid esters, in particular triglycerides of fatty acids, lanolin, natural and synthetic oils or waxes and emulsifiers in the presence of water.
  • FAA comprises, for example, fatty alcohols, fatty acids, fatty acid esters, in particular triglycerides of fatty acids, lanolin, natural and synthetic oils or waxes and emulsifiers in the presence of water.
  • a lower alcohol such as ethanol
  • a glycerol such as propylene glycol
  • a polyol such as glycerol
  • composition according to the invention may also be in the form of an alcoholic gel which comprises one or more lower alcohols or polyols, such as ethanol, propylene glycol or glycerol, and a thickener, such as siliceous earth.
  • the oily-alcoholic gels also comprise natural or synthetic oil or wax.
  • the solid sticks consist of natural or synthetic waxes and oils, fatty alcohols, fatty acids, fatty acid esters, lanolin and other fatty substances. If a composition is formulated as an aerosol, the customary propellants, such as alkanes, fluoroalkanes and chlorofluoroalkanes, are generally used.
  • the cosmetic composition may also be used to protect the hair against photochemical damage in order to prevent changes of colour shade, bleaching or damage of a mechanical nature.
  • a suitable formulation is in the form of a rinse-out shampoo, lotion, gel or emulsion, the composition in question being applied before or after shampooing, before or after colouring or bleaching or before or after permanent waving. It is also possible to select a composition in the form of a lotion or gel for styling or treating the hair, in the form of a lotion or gel for brushing or blow-waving, in the form of a hair lacquer, permanent waving composition, colorant or bleach for the hair.
  • the composition having light-protection properties may comprise various adjuvants used in this type of composition, such as surfactants, thickeners, polymers, softeners, preservatives, foam stabilisers, electrolytes, organic solvents, silicone derivatives, oils, waxes, antigrease agents, dyes and/or pigments which colour the composition itself or the hair, or other ingredients usually used for hair care.
  • adjuvants used in this type of composition such as surfactants, thickeners, polymers, softeners, preservatives, foam stabilisers, electrolytes, organic solvents, silicone derivatives, oils, waxes, antigrease agents, dyes and/or pigments which colour the composition itself or the hair, or other ingredients usually used for hair care.
  • the present invention furthermore relates to a process for the preparation of a composition which is characterised in that one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA are mixed with a cosmetically or dermatologically carrier, and to the use of one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA for the preparation of a
  • compositions according to the invention can be prepared here with the aid of techniques which are well known to the person skilled in the art.
  • the mixing can result in dissolution, emulsification or dispersal of FAA derivatives.
  • the positive effects of one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA give rise to their particular suitability for use in cosmetic or pharmaceutical compositions. Due to their action, one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA are preferable also suitable as medicament ingredients.
  • One or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA can be used, for example, for preventative treatment of inflammation and allergies of the skin and in certain cases for preventing certain types of cancer.
  • One or more of the compounds according to formula (I) 1 preferably
  • FAA and/or its derivatives, and especially FAA are particularly suitable for the preparation of a medicament for the treatment of inflammation, allergies and irritation, in particular of the skin. It is furthermore possible to prepare medicaments which act as a vein tonic, as cuperose inhibitor, as chemical, physical or actinic erythema inhibitor, as agent for the treatment of sensitive skin, as decongestant, as desiccant, as slimming agent, as anti-wrinkle agent, as stimulator for the synthesis of components of the extracellular matrix, as strengthening agent for improving skin elasticity, and as anti- ageing agent. Furthermore, one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA exhibit antiallergic and antiinflammatory and antiirritative actions. They are therefore suitable for the preparation of medicaments for the treatment of inflammation or allergic reactions.
  • Skin has been among the first organs analysed using DNA microarrays.
  • Epidermal keratinocytes have been the target of many studies because they respond to a rich variety of inflammatory and immunmodulating cytokines, hormones, vitamins, ultraviolet (UV) light, toxins and physical injury.
  • cytokines include IL-1, 5-HT1 and 5-HT1
  • UV ultraviolet
  • Table 1 Genes deregulated by treatment of skin with FAA
  • GeneOntplogy biological process categories were scored for an enrichment of de-regulated genes using a hypergeometric test. Whereas no significantly enriched categories were found for the up-regulated genes, the categories shown in Table 2 exhibit a significant overrepresentation of down-regulated genes.
  • Table 2 Gene Ontology biological processes with an enrichment of genes that are down-regulated by FAA.
  • Extracellular matrix (ECM) remodeling comprises the processes like collagen catabolic process, tissue remodeling and wound healing.
  • the adhesion of cells to the extracellular matrix (ECM) is a dynamic process, mediated by a series of matrix-associated and cell-surface molecules that interact with each other in a spatially and temporally regulated manner.
  • the extracellular matrix is the extracellular part of tissue that usually provides structural support to the cells in addition to performing various important functions. Formation of the ECM is essential for processes like growth, wound healing, and fibrosis. The extracellular matrix is the defining feature of connective tissue.
  • the ECM and cell adhesion and migration processes in fact plays at least three important roles relevant in cosmetics: i) Mechanical: tensile and compressive strength and elasticity, ii) Protection: buffering against extracellular change and retention of water, iii)
  • the ECM's main components are various glycoproteins like collagens, fibrin, elastin, fibronectins, laminins, and nidogens and other molecular compounds like proteoglycans and hyaluronic acid.
  • the effects of FAA on the gene level give us new insights into the potential action of the compound FAA in a variety of skin/hair regeneration processes and disorders. Interactions with integrins and thus promotion of extracellular matrix proteins and a consecutive increased of matrix organization capacity, may cause anti-wrinkle effects, anti-inflammation effects and promotion of hair growth in hair cycles and regarding to the hair follicle development.
  • S100 calcium binding protein A7 and S100 calcium binding protein A12 are downregulated genes after treatment of skin cells with FAA.
  • S100A7A may be involved in epidermal differentiation and inflammation and might therefore be important for the pathogenesis of psoriasis and other diseases.
  • the S100A7 protein also known as psoriasin, has important functions as a mediator and regulator in skin differentiation and disease (psoriasis), in breast cancer, and as a chemotactic factor for inflammatory cells (Kulski et al., Journal of Molecular Evolution (2003), 56(4), 397-406).
  • Lener et al. investigate genes involved in the natural aging process of the human skin. They found that in total 105 genes change their expression over 1.7-fold during the aging process in the human skin.
  • S100A7 has been described as a gene that is up-regulated in old skin (T. Lener et al., Experimental Gerontology 41 (2006), 387-397).
  • S100 proteins are the largest subgroup of Ca 2+ binding proteins with the EF- hand structural motif. A unique feature of this protein family is that individual members are localized in specific cellular compartments. For example, various S 100 proteins are expressed in very restricted regions of the hair follicle (Kizawa K et al., Methods MoI Biol. (2005).
  • Extracellular proteases are crucial regulators of cell function.
  • the family of matrix metalloproteinases (MMPs) has classically been described in the context of extracellular matrix (ECM) remodeling, which occurs throughout life in diverse processes that range from tissue morphogenesis to wound healing. Recent evidence has implicated MMPs in the regulation of other functions, including survival, angiogenesis, inflammation and signaling.
  • Skin aging is influenced by several factors, including genetics, environmental exposure (ultraviolet (UV) irradiation, , xenobiotics, mechanical stress ), hormonal changes, and metabolic processes.
  • environmental exposure ultraviolet (UV) irradiation
  • xenobiotics xenobiotics
  • mechanical stress xenobiotics
  • hormonal changes e.g., hormonal changes, and metabolic processes.
  • the typical appearance of photoaged and chronologically aged human skin can be readily
  • MAP kinase activation results in induction of transcription factor AP-1 that is a major effector of the MAP kinase pathways.
  • AP-1 regulates expression of many genes involved in the regulation of cellular growth and differentiation. Transcription of several MMP (matrix-metalloproteinase) family members is strongly regulated by AP- 1. Several MMPs are upregulated by AP-1.
  • MMP-1 interstitial collagenase or collagenase 1
  • MMP-9 gelatinase B
  • MMP-3 stromelysin 1
  • MMP-1 , MMP-3, and MMP-9 have the capacity to completely degrade mature fibrillar collagen in skin. Consistent with this, increased collagen breakdown has been demonstrated within 24 h after UV irradiation in human skin in vivo. Thus, UV irradiation of human skin causes extracellular matrix degradation via induction of transcription factor AP-1 , and subsequent increased MMP production.
  • MMPs are secreted from keratinocytes and fibroblasts and break down collagen and other proteins that comprise the dermal extracellular matrix. Imperfect repair of the dermal damage impairs the functional and structural integrity of the extracellular matrix. Repeated sun exposure causes accumulation of dermal damage that eventually results in characteristic wrinkling of photodamaged skin (Gary J. Fisher et al., ARCH DERMATOL, vol. 138 (2002).
  • the primary role of MMP enzymes is to recycle skin matrix, particularly the structural proteins collagen and elastin. Reduces MMP activities degrade skin connective tissue and prevents loss of procollagen expression.
  • the downregulated MMP genes after treatment of skin cells with FAA are MMP3, 9, 10. It is likely that downregulation of MMPs results in increase of collagen fibrils. Also, collagen-alpha type I (COL1A1), collagen-type Vl
  • COL6A1 Fibroblast growth factor 2 (FGF2), fibronectin 1 (FN 1) and insulin-like growth factor binding protein 3 (IGFBP3) and hyaluronan synthase 2 (HAS2) have been upregulated.
  • FGF2 Fibroblast growth factor 2
  • FN 1 fibronectin 1
  • IGFBP3 insulin-like growth factor binding protein 3
  • HAS2 hyaluronan synthase 2
  • MMP9 is strongly down-regulated after treatment of skin cells with FAA. This motivates the hypothesis that FAA activates upregulation of dermal fibroblast collagen production and downregulation of collagen degradation.
  • UV irradiation from the sun reduces production of type I procollagen (COLI), the major structural protein in human skin.
  • Photo-aging is the most common form of skin damage and is associated with skin carcinoma.
  • FAA Aquaporin 3, TNFSF9 (tumor necrosis factor (ligand) superfamily, member 9), MMP10, Keratin 1, Loricrin [A. Pisarchik et al. / Gene 341 (2004) 199-207]
  • BMP stimulate differentiation of epidermal and hair follicle keratinocytes, inhibit initiation of hair growth, promote melanocyte proliferation and modulate melanogenesis, as well as an increase in calcitonin gene-related peptide expression in sensory neurons innervating skin.
  • Downregulation of BMP-2 retards the entry in catagen phase in hair follicle cycling.
  • Inhibition of BMP signaling also results in the generation of new intestinal stem cell proliferation (noggin is the natural inhibitor of BMP signaling - L.M. Hogan et al., The EMBO Journal (2000)).
  • BMP-2 suppresses proliferative activity and support diffentiation, while FGF2 (fibroblast growth factor-2) and Follistatin stimulates hair follicle development in vitro and induces anagen phase of hair follicle growth (Paus R., Physiol
  • BMP-2 is downregulated, while FGF2 and transmembrane protein with EGF-like domain and two follistatin-like domains 2 (TMEFF2) are significantly upregulated.
  • Sphingosine-1 -phosphate is the ligand for a family of specific G protein coupled receptors (GPCRs) that regulate a wide variety of cellular functions, including cytoskeletal rearrangements and cell motility. Due to the pivotal role of S1 P, its levels are low and tightly regulated in a spatial-temporal manner through its synthesis catalyzed by sphingosine kinases (SphK) and degradation by an S1P lyase and specific S1P phosphatases (SPP). In the treated skin with FAA, sphingosine-1 -phosphate phosphatase 2 (SGPP2) expression is downregulated. It is known that the downregulation of SPP-1 enhanced migration towards EGF [Herve Le Stunff et al., J. Biol. Chem, 10., 2004].
  • EGF Extracellular Growth Factor
  • EGFL8 EGF-like-domain
  • EGF has been shown to be a key player in the cell growth and differentiation process.
  • DPT Dermatopontin
  • ECM extracellular matrix
  • the keratinization process is affected by FAA , which motivates its use for the treatment of psoriasis.
  • the genome-wide expression signature of human skin treatment with FAA is compared to a database of 1667 genome-wide expression signatures from the public domain and in-house microarray experiments.
  • a computational method is used that quantifies the similarity between any two given expression signatures by a Kolmogorow- Smirnov statistic.
  • the expression signature of human skin treatment with FAA is compared to all database signatures, the second most similar among all 1667 database signatures is from a study comparing non-lesional and lesional skin from psoriasis vulgaris patients (Reischl et al., J Invest Dermatol. 127 (2007), 163-9).
  • compositions preferably non-therapeutic compositions, cosmetic compositions and/or topical compositions, comprising the
  • UV-PearlsTM OMC stands for the composition with the INCI: water (for EU: Aqua), Ethylhexyl Methoxycinnamate, Silica, PVP, Chlorphenesin, BHT; this composition is commercially available under the name Eusolex ⁇ UV PearlTM OMC from Merck KGaA, Darmstadt.
  • the other UV Pearl products indicated in the tables are each of analogous composition with OMC replaced by the UV filter indicated.
  • Table 6a O/W emulsions (amounts in % w/w )
  • Table 6b (amounts in % w/w)

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Abstract

The invention relates to flavone acetic acid, its derivatives and its use in compositions, especially topical, cosmetic and/or personal care compositions, and compositions containing flavone acetic acid and/or its derivatives.

Description

Use of FAA and its derivatives in cosmetics and dermatology
The present invention relates to compositions, preferably compositions for topical use, comprising one or more compounds of formula (I), which preferably are flavone acetic acid and/or derivatives thereof, selected from
wherein
Z is O, S or NH,
R1, R2 and R3 are independently of each other selected from
- OH, OA, NO2, NH2, NHA, NA2, NHCOA, CONH2, CONHA and CONA2, preferably OH, NO2, NH2, NHCOCH3 and CONH2, wherein A is independently selected from Cr to C6-alkyl groups,
- halogen and trifluoromethyl, preferably Cl, F and trifluoromethyl;
- methyl, ethyl and straight-chain or branched C3- to C2o-alkyl groups, preferably methyl, ethyl and straight-chain or branched C3- to C12-alkyl groups;
- ethenyl and straight-chain or branched C3- to C2o-alkenyl groups, preferably ethenyl and straight-chain C3- to C6-alkenyl groups;
- methoxy, ethoxy and straight-chain or branched C3- to C20-alkoxy groups, preferably methoxy groups;
- formyl, acetyl and straight-chain or branched C3- to C2o-acyl groups, preferably acetyl groups;
- hydroxymethyl, hydroxyethyl and straight-chain or branched C3- to C2o- hydroxyalkyl groups, where the hydroxyl group may be bonded to a primary or secondary carbon atom of the chain and furthermore the alkyl chain may also be interrupted by oxygen, preferably hydroxymethyl and hydroxyethyl groups;
- Ci- to C2o-carboxyl groups, preferably C1- to C6-carboxyl groups;
- -0-(CH2)I-COOH, where I = 1 to 20, preferably I = 1 to 6;
5 - C3- to Cio-cycloalkyl groups and/or C3- to Ci2-cycloalkenyl groups, where the rings may each also be bridged by -(CH2Jm- groups, where m = 1 to 3, preferably cyclopentyl and cyclohexyl groups, and
- phenyl, halogenophenyl, phenoxy and benzoyl groups, preferably phenyl, halogenophenyl and phenoxy groups;
10 where n = 0 to 6, o = 0 to 3, and p = 0 to 5,
and/or a salt or solvate thereof, preferably as active ingredient, and optionally one or more topically acceptable vehicles.
Preferably, the one or more compounds according to formula (I) are selected from compounds of formula (II)
wherein
R1 , R2 and R3 are independently of each other selected from
OH, OCH3, NO2, NH2, NHCOCH3, COOH1 CONH2, COCH3, F, Cl, CF3;
- methyl, ethyl, straight-chain or branched C3- to C12-alkyl groups;
25
- phenyl, fluorophenyl and/or phenoxy groups;
where o = O, 1 , 2 or 3 and p = O, 1 , 2, 3, 4 or 5,
and/or a salt or solvate thereof as active ingredient and one or more topically acceptable vehicles.
Examples of such flavone acetic acid derivatives according to above formula on
are given in EP0080934 and EP0341104, the disclosures of which are incorporated herein by reference in their entirety. The European patent EP0080934A1 discloses 57 formulas of flavone acetic acid derivatives. The following FORMULAS thereof have been selected as preferred specific examples for the compounds according to formula (I) of the present invention:
4-OXO-4H-[1 l-BENZOPYRAN-8-
ACETIC ACID / flavone acetic
acid / FAA [FORMULA 2]
6-METHYL-2-PHENYL-4-OXO- 6-METHOXY-2-PHENYL-4-OXO-4H- 4H-[1 ]-BENZOPYRAN-8-ACETIC [1]-BENZOPYRAN-8-ACETIC ACID
ACID [FORMULA 31]
[FORMULA 16]
6-HYDROXY-2-PHENYL-4-OXO- 2-(4-METHOXYPHENYL)-4-OXO-4H- 4H-[1]-BENZOPYRAN-8-ACETIC [1]-BENZOPYRAN-8-ACETIC ACID
ACID [FORMULA 46]
[FORMULA 32]
2-(3,4-DIPHENYLPHENYL)-4- OXO-4H-[1 l-BENZOPYRAN-8- ACETIC ACID [FORMULA 55]
The European patent EP0341104B1 discloses 131 formulas of flavone acetic acid derivatives. Suitable for use according to the invention, the disclosure of which is incorporated in its entirety into this application by reference, the following Formulas thereof have been also selected as preferred specific examples for the compounds according to formula I of the present invention:
3-METHOXY-4-OXO-2-PHENYL- 4H-[1]-BENZOPYRAN-8-ACETIC
ACID
[Formula 4] -METHOXY-4-OXO-2-PHENYL- 2-(2-METHOXYPHENYL)-4-OXO-4H-H-[1 l-BENZOPYRAN-8-ACETIC [1]-BENZOPYRAN-8-ACETIC ACID
ACID [Formula 6] [Formula 5]
-HYDROXY-4-OXO-2-PHENYL- HYDROXY-5-OXO-4-PHENYL-2-4H-H-[1]-BENZOPYRAN-8-ACETIC [1]-BENZOPYRAN-8-ACETIC ACID
ACID [Formula 8] [Formula 7]
-HYDROXY-4-OXO-2-PHENYL- 2-(2-HYDROXYPHENYL)-4-OXO-4H-H-[1 ]-BENZOPYRAN-8-ACETIC [1]-BENZOPYRAN-8-ACETIC ACID
ACID [Formula 10] [Formula 9]
2-(4-HYDROXYPHENYL)-4-OXO- 4H-[1 J-BENZOPYRAN-8-ACETIC 2-(2-PHENOXYPHENYL)-4-OXO-4H-
ACID [1]-BENZOPYRAN-8-ACETIC ACID [Formula 11] [Formula 14]
6-FLUORO-4-OXO-2-PHENYL-4H- 2-(2-FLUOROPHENYL)-4-OXO-4H- [1]-BENZOPYRAN-8-ACETIC ACID [1]-BENZOPYRAN-8-ACETIC ACID
[Formula 15] [Formula 16]
2-(4-FLUOROPHENYL)-4-OXO-4H- 2-(3-FLUOROPHENYL)-4-OXO-4H-
[1]-BENZOPYRAN-8-ACETIC ACID [1]-BENZOPYRAN-8-ACETIC ACID
[Formula 17] [Formula 18]
2-(4-PHENYLPHENYL)-4-OXO-4H- 2-(4-CHLOROPHENYL)-4-OXO-4H-
[1]-BENZOPYRAN-8-ACETIC ACID [1]-BENZOPYRAN-8-ACETIC ACID
[Formula 19] [Formula 20]
2-(4-CARBOXYPHENYL)-4-OXO- 4H-[1 ]-BENZOPYRAN-8-ACETIC 2-(4-(2-FLUOROPHENYL)-PHENYL)-
ACID 4-OXO-4H-[1 ]-BENZOPYRAN-8- [Formula 21] ACETIC ACID [Formula 22]
2-(2-NITROPHENYL)-4-OXO-4H- 2-(3-NITROPHENYL)-4-OXO-4H-[1 ]-
[1]-BENZOPYRAN-8-ACETIC ACID BENZOPYRAN-8-ACETIC ACID
[Formula 23] [Formula 24]
2-(4-NITROPHENYL)-4-OXO-4H- 2-(3-AMINOPHENYL)-4-OXO-4H-[1]-
[1]-BENZOPYRAN-8-ACETIC ACID BENZOPYRAN-8-ACETIC ACID
[Formula 25] [Formula 26]
2-(4-AMINOPHENYL)-4-OXO-4H- 2-(2-AMINOPHENYL)-4-OXO-4H-[1]-
[1]-BENZOPYRAN-8-ACETIC ACID BENZOPYRAN-8-ACETIC ACID
[Formula 27] [Formula 105]
2-(2-CHLOROPHENYL)-4-OXO-4H- 2-(3-CHLOROPHENYL)-4-OXO-4H-
[1]-BENZOPYRAN-8-ACETIC ACID [1]-BENZOPYRAN-8-ACETIC ACID
[Formula 106] [Formula 107]
-(4-ACETAMIDOPHENYL)-4-OXO- 2-(3-NITRO-4-CHLOROPHENYL)-4- 4H-[1]-BENZOPYRAN-8-ACETIC OXO-4H-[1 ]-BENZOPYRAN-8-
ACID ACETIC ACID [Formula 113] [Formula 111]
2-(2,4-DIMETHOXYPHENYL)-4- 2-(4-CARBAMOYLPHENYL)-4-OXO-
OXO-4H-[1 ]-BENZ0PYRAN-8- 4H-[1 ]-BENZOPYRAN-8-ACETIC
ACETIC ACID ACID
[Formula 114] [Formula 116]
,5 DIMETHOXYPHENYL)-4- 2-(4-HEXYLPHENYL)-4-OXO-4H-[1 ]-
OXO-4H-[1 ]-BENZOPYRAN-8- BENZOPYRAN-8-ACETIC ACID
ACETIC ACID [Formula 123]
[Formula 120]
2-(3-METHYLPHENYL)-4-OXO-4H- 2-(4-UNDECYLPHENYL)-4-OXO-4H-
[1J-BENZOPYRAN-8-ACETIC ACID [1]-BENZOPYRAN-8-ACETIC ACID
[Formula 124] [Formula 126]
2-(4-TRIFLUOROMETHYLPHENYL)-
2-(3-NITRO-4-PHENYLPHENYL)-4- 4-OXO-4H-[1 ]-BENZOPYRAN-8- OXO-4H-[1 ]BENZOPYRAN-8- ACETIC ACID [Formula 128] ACETIC ACID [Formula 127]
2-(3-NITRO^-METHOXYPHENYL)- 2-(4-TERBUTYLPHENYL)-4-OXO-4H-
4-OXO-4H-[1 l-BENZOPYRAN-8- [1]-BENZOPYRAN-8-ACETIC ACID
ACETIC ACID [Formula 130] [Formula 131]
FORMULA 2 of EP0080934A1 ,
preferably also named mitoflaxone, 2-(4-oxo-2-phenylchromen-8-yl)acetic acid [IUPAC], 4-oxo-4H-[1]-benzopyran-8-acetic acid, flavone acetic acid or FAA, and/or a salt thereof, is the most preferred compound in the
composition, especially the composition for topical use, according to the present invention.
US6,916,831B2 describes FAA, a semi-synthetic flavone, and its analogs as antitumor agents. It has excellent activity against murine colon
adenocarcinoma 38 and a broad spectrum of slowgrowing solid tumors that are usually insensitive to most cytotoxic drugs (J. Plowman, et al., Cancer Treatment Reports 1986, 70, 631 ; O. Atassi et al., Pur. J. Med. Chenz. Chin. Ther. 1995, 20, 393). In contrast to its solid tumor activity, FAA shows poor activity against murine leukemia cell lines (P388 and L1210). Because of its unique preclinical solid tumor activity, FAA has been evaluated in clinical trials (M. Bihhy and J. Double, J. A. Anti-Cancer drugs 1993, 4, 3). US6.559133B2 describes FAA and other flavone-8-carboxylic acids, like flavone-8-propionic acid and flavone-8-butyric acid, for the treatment on thrombosis and vasoconstriction.
In the present invention one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA are used as one or more compounds of a composition in the field of cosmetics and
dermatology. This means, one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA are preferably topically applied. In this respect, topically applied preferably means that the compositions containing one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA are generally applied on the surface of the body. In this regard, the surface of the body preferably includes the skin, the hair, especially the hair roots, and/or mucous membranes. Preferably, a topical application to a certain area of the skin is affecting the area to which it is applied. Thus, topically applied should preferably be understood as the opposite of systemically applied.
The human skin is subject to certain ageing processes, some of which are attributable to intrinsic processes (chronoageing) and some of which are attributable to exogenous factors (environmental, for example photoageing); see Shapiro et al. Nutrition 2001; 17:839-844. In addition, temporary or even lasting changes to the skin picture can occur, such as acne, greasy or dry skin, keratoses, rosaceae, light-sensitive, inflammatory, erythematous, allergic or autoimmune-reactive reactions, such as dermatosis and
photodermatosis.
The exogenous factors include, in particular, sunlight or artificial radiation sources having a comparable spectrum, and compounds which can be formed by the radiation, such as undefined reactive photoproducts, which may also be free-radical or ionic. These factors also include cigarette smoke and the reactive compounds present therein, such as ozone, free radicals, for example the hydroxyl free radical, singlet oxygen and other reactive oxygen or nitrogen compounds which interfere with the natural physiology or morphology of the skin.
The influence of these factors can result, inter alia, in direct damage to the DNA of the skin cells and to the collagen, elastin or glycosaminoglycan molecules of the extracellular matrix, which are responsible for the strength of skin. In addition, the signal transduction chains, which are terminated by the activation of matrix-degrading enzymes, may be affected. Important representatives of these enzymes are the matrix metalloproteinases (MMPs, for example collagenases, gelatinases and stromelysins), whose activity is additionally regulated by TIMPs (tissue inhibitors of matrix
metalloproteinases).
The consequences of the above-mentioned ageing processes are thinning of the skin, weaker interlacing of epidermis and dermis, and a reduction in the number of cells and the supplying blood vessels. These results in the formation of fine lines and wrinkles, the skin becomes leathery, and pigment defects can occur.
Furthermore the skin contains an extensive network of macromolecules (e.g., polysaccharides and proteins) that make up the extracellular matrix (ECM). Specific cells within the ECM secrete polysaccharide glycosaminoglycans and fibrous proteins (Alberts et al., Molecular Biology of the Cell, p. 802, New York: Garland Publishing, Inc., 1989). Polysaccharide glycosaminoglycans are long, unbranched polysaccharides composed of repeating disaccharide units. These structures are sometimes linked to a core protein to form larger structures known as proteoglycans (Alberts et al., Molecular Biology of the Cell, p. 803, New York: Garland Publishing, Inc., 1989). The fibrous proteins of the ECM consist of structural proteins such as elastin and collagen, which account for about 70% of the dry weight of the dermis (Lahmann et al., Lancet, 357(9260):935-6, 2001), and adhesive proteins such as fibronectin and laminin. The structure of the ECM is typically characterized by
polysaccharide glycosaminoglycans and proteoglycans forming a gel-like substance in which the fibrous proteins are embedded (Alberts et al., Molecular Biology of the Cell, p. 803, New York: Garland Publishing, Inc.,
1989).
As skin ages, its physiology goes through many changes. These changes are caused by structural and/or functional transformations of the ECM that usually take place during the passage of time and during over exposure to sunlight. Aging or long-term exposure to UV light is associated with i) a decrease in collagen synthesis; ii) an increase in matrix metalloprotease (MMP) activity; and iii) a reduction of the expression of tissue inhibitors of metalloproteases (TIMP). The combined actions of these factors result in a progressive degradation of the ECM (Thibodeau, Allured's Cosmetic & Toiletries Magazine, 115(11):75-82, 2000).
The integrity of ECM components, in particular collagen, is important to ensure that the epidermal layer of the skin firmly anchors to the dermal layer of the skin. Degradation of collagen at the dermo-epidermal junction by proteases (e.g., matrix metalloproteases) weakens dermal adhesion, which eventually leads to the appearance of wrinkles and a reduction in the firmness and elasticity of the skin (Thibodeau, Allured's Cosmetic & Toiletries Magazine, 115(11):75-82, 2000).
Matrix metalloproteases (MMPs, e.g., gelatinase, Collagenase and
stromelysin), which digest collagen, gelatin (denatured collagen) and other components of the ECM, are important in normal development.
There are a number of different MMPs that are specific for the various ECM components. For instance, gelatinase A (MMP-2) is primarily responsible for the degradation of the helical domains of type IV collagen, the principal collagen of basement membranes, while interstitial collagenase (MMP-1) is more selective for type I collagen (Thibodeau, Allured's Cosmetic & Toiletries Magazine, 115(11):75-82, 2000). MMPs are regulated by a number of inhibitor proteins, termed tissue inhibitors of metalloprotease (TIMPs), and by the relationship between the MMPs themselves.
The enzymatic balance between MMPs is naturally controlled by the presence of tissue inhibitors of matrix metalloproteases. Aging and environmental insults, such as UV light, disrupt this equilibrium in favor of the over expression of these enzymes. MMPs of type I (i.e., interstitial collagenase, MMP-1) are responsible for degradation of skin collagen fibers, particularly during photo-damage, and this degradation of collagen fibers contributes to the visible effects of UV damage (i.e., wrinkling, loss of elasticity and dilation of surface micro-capillary vessels).
Therefore, in order to reduce the visible affects caused by UV exposure and MMPs1 it is necessary to inhibit or reduce the activity of MMPs such as MMP- 9, MMP-3, and MMP-10 to quench reactive free-radicals like superoxide anions and hydroxyl radicals, and/or to chelate elements such as iron and copper to prevent or reduce oxidative stress to the skin.
This objective of the present invention is preferably achieved by using one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA in cosmetics and dermatology. According to studies with Affymetrix oligonucleotide microarrays in a human skin model the transcriptional levels of the genes MMP-9, MMP-10, and MMP-3 show downregulation after four days of treatment with FAA. A statistical analysis of over-represented biological process categories (GeneOntology) among the regulated genes after treatment with FAA indicates down-regulation of the collagen catabolic process and keratinization. One or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA are effective to reduce or prevent aging through the enhancing of collagen and also to treat acne and other skin diseases.
One or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA can preferably be shown to be particular useful as anti-ageing, anti-inflammatory and anti-acne ingredients in dermatological and cosmetic compositions (alone or in combination with other actives). Therefore, the invention relates to the use of one or more of the compounds according to formula (I), preferably FAA and/or its
derivatives, and especially FAA for such purposes.
The invention also relates to the use of one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA in the preparation of cosmetic compositions for the use as anti-ageing, anti-inflammatory and for the treatment of acne. Preferably, the invention also relates to the use of one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA in the preparation of cosmetic compositions for the use as modulators of hair growth and/or hair loss and preferably also treatment of hyperpigmentation and/or modulation of pigmentation, including depigmentation.
One or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA can be used as free acid but also as one of their salts with organic or inorganic bases, of the salts formed with metals and in particular alkali, alkaline earth and transition metals (such as sodium, potassium calcium, magnesium or aluminium) or with bases, such as ammonia or secondary or tertiary amines (such as diethylamine,
triethylamine, piperidine, piperazine or morpholine), or with basic amino acids or with osamines (such as meglumine) or with aminoalcohols (such as 3- aminobutanol and 2-aminoethanol). In particular, FAA can be used in form of its alkali metal salts, preferably its potassium or sodium salt, and especially its sodium salt.
The term "dermatologically acceptable", as used herein, preferably means that the composition or components described are preferably suitable for use in contact with human skin without risk of toxicity, incompatibility, instability and/or allergic response, and the like.
All terms such as "skin ageing", "signs of skin ageing", "topical application", and the like are preferably used in the sense in which they are generally and widely used in the art of developing, testing and marketing cosmetic and personal care products.
The term "cosmetic composition" or preferably more briefly just "composition" in accordance with the present invention preferably relates to a formulation that can be used for cosmetic purposes, purposes of hygiene and/or as a basis for delivery of one or more pharmaceutical ingredients. It is also possible that these formulations are used for two or more of these purposes at one time. Thus, the terms "cosmetics," "cosmetic composition" and/or "composition"as used herein, preferably include without limitation, lipstick, mascara, rouge, foundation, blush, eyeliner, lipliner, lip gloss, facial or body powder, sunscreens and blocks, nail polish, mousse, sprays, styling gels, nail conditioner, whether in the form of creams, lotions, gels, ointments, emulsions, colloids, solutions, suspensions, compacts, solids, pencils, spray- on formulations, brush-on formulations and the like.
"Personal care products" preferably include, without limitation, bath and shower gels, shampoos, conditioners, cream rinses, hair dyes and coloring products, leave-on conditioners, sunscreens and sunblocks, lip balms, skin conditioners, cold creams, moisturizers, hair sprays, soaps, body scrubs, exfoliants, astringents, depilatories and permanent waving solutions, antidandruff formulations, antisweat and antiperspirant compositions, shaving, preshaving and after shaving products, moisturizers, deodorants, cold creams, cleansers, skin gels, rinses, whether in solid, powder, liquid, cream, gel, ointment, lotion, emulsions, colloids, solutions, suspensions, or other form. "Pharmaceutical preparations" in accordance with the present invention preferably include, without limitation, carriers for dermatological purposes, including topical and transdermal application of pharmaceutically active ingredients. These can be in the form of gels, patches, creams, nose sprays, ointments, lotions, emulsions, colloids, solutions, suspensions, powders and the like. Compositions in accordance with the invention preferably include cosmetics, personal care products and pharmaceutical preparations. Compositions in accordance with the invention especially preferably include cosmetics or personal care products.
The terms "skin ageing" or "signs of skin ageing" preferably include, but are not limited to, all outward visibly and tactilely perceptible manifestations as well as any other macro or micro effects due to skin ageing. Such signs may be induced or caused by intrinsic factors or extrinsic factors, e.g.
chronological ageing and/or environmental damage. The signs may result from processes which preferably include, but are not limited to, the
development of textural discontinuities, such as wrinkles and coarse deep wrinkles, skin lines, crevices, bumps, large pores (e.g. associated with adnexal structures such as sweat gland ducts, sebaceous glands, or hair follicles), or unevenness or roughness of the skin, loss of skin elasticity (loss and/or in activation of functional skin elastin), sagging (including puffiness in the eye area and jowls), loss of skin firmness, loss of skin tightness, loss of skin recoil from deformation, discoloration (including (black) under eye circles), blotching, sallowness, hyperpigmented skin regions such as age spots and freckles, keratoses, abnormal differentiation, hyperkeratinization, elastosis, collagen breakdown, and other histological changes in the stratum corneum, dermis, epidermis, the skin vascular system (e.g., telangiectasia or spider vessels), and underlying tissues, especially those proximate to the skin. Particularly preferred in accordance with the present invention, the signs of skin aging are wrinkles and the compositions of the present invention are, in certain preferred embodiments, useful in fighting, treating or preventing wrinkles.
As used herein, prophylactically regulating a skin condition preferably includes delaying, minimizing and/or preventing visible and/or tactile discontinuities in skin (e.g., texture irregularities in the skin which may be detected visually or by feel), including signs of skin aging.
As used herein, therapeutically regulating skin condition preferably includes ameliorating, e.g., diminishing, minimizing and/or effacing, discontinuities in skin, including signs of skin aging. Some of the products produced using the compositions of the present invention and indeed the compositions
themselves may be used for prophylactically or therapeutically regulating a skin condition.
Some of the products and compositions of the present invention are useful for improving skin appearance and/or feel of skin exhibiting signs of skin aging. For example, preferred compositions of the present invention are useful for regulating the appearance of skin conditions by providing an immediate visual improvement in skin appearance following application of the composition to the skin. Generally speaking, compositions of the present invention which further contain particulate materials will be most useful for providing the immediate visual improvement. Some of the compositions of the present invention may also provide one or more additional benefits, preferably selected from stability of the formulation, absence of significant (consumer-unacceptable) skin irritation, anti- inflammatory activity and/or good aesthetics.
In certain preferred aspects, the present invention is useful for improving the physiological state and/or the physical appearance of human skin, in particular to reduce the signs of skin aging that are generated by sun exposure, physical and hormonal stress, abrasion, nutritional effects and other similar causes. The compositions may often be used to prevent the signs of aging and/or to treat them in order to afford the consumer who uses them, a more youthful appearance.
Accordingly, the instant invention more preferably relates to:
A composition, preferably a non-therapeutic composition comprising one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA and/or a salt or solvate thereof.
A composition for topical use comprising
i) one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA and/or a salt or solvate thereof, ii) one or more skin-tolerated vehicles, and optionally
iϋ) one or more further active compounds having a skin-care and/or inflammation-inhibiting action.
A composition as described above/below, wherein one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA are typically employed in accordance with the invention in amounts of from 0.01 to 20% by weight, preferably in amounts of from 0.1% by weight to 10% by weight and particularly preferably in amounts of from 1 to 8% by weight.
A composition comprising one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA and at least one further skin-care ingredient and at least one carrier which is suitable for topical applications. Use of one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA for the manufacture of a composition, preferably a non-therapeutic composition and especially preferably a cosmetic composition or topical composition.
Use of one or more of the compounds according to formula (I), preferably
FAA and/or its derivatives, and especially FAA for the preparation of a composition which is suitable for the prophylaxis and/or treatment of skin diseases which are associated with defective keratinisation relating to differentiation and cell proliferation, in particular for the treatment of acne vulgaris, acne comedonica, polymorphic acne, acne rosaceae, nodular acne, acne conglobata, age-related acne, acne occurring as a side effect, such as acne Solaris, medicament-related acne or acne professionalis, for the treatment of other defects of keratinisation, in particular ichthyosis,
ichthyosiform states, Darier's disease, keratosis palmoplantaris, leukoplakia, leukoplakiform states, skin and mucosal (buccal) eczema (lichen), for the treatment of other skin diseases which are associated with defective keratinisation and have an inflammatory and/or immunoallergic component, and in particular all forms of psoriasis relating to the skin, mucous
membranes and finger- and toenails, and psoriatic rheumatism and skin atopy, such as eczema, or respiratory atopy, or also hypertrophy of the gums.
Use of one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA for the care, preservation or improvement of the general state of the skin or hair.
Use of one or more of the compounds according to formula (I), preferably
FAA and/or its derivatives, and especially FAA for the prophylaxis against or reduction of skin unevenness, such as wrinkles, fine lines, rough skin or large-pored skin.
Use of one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA for the prophylaxis against time- and/or light-induced ageing processes of the human skin or human hair, in particular for prophylaxis against dry skin, wrinkle formation and/or pigment defects, and/or for the reduction or prevention of the harmful effects of UV rays on the skin.
Preferably, one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA and the
compositions containing it preferably appear to have a benefit in tissue regeneration. This is believed to be due to their ability to modulate and preferably stimulate the production of certain advantageous biomolecules, including, but not limited to, collagen I, fibronectin, collagen IV and/or hyaluronic acid, in skin cells.
Thus, one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA and compositions containing it can preferably be used to improve the visible signs of ageing in human skin, including fine lines, wrinkles, enlarged pores, roughness, dryness, and other skin texture defects such as the stretchmarks (as caused by pregnancy, trauma or other influences) bags under the eyes, also called "puffy eyes" and dark (under eye) circles, both preferably caused by thinning of the skin, insufficient blood circulation and/or slack tissue, especially on repeated topical application.
Thus, further subjects of the instant invention preferably comprise:
A method and/or a composition for reducing the visible signs of ageing, preferably for reducing the visible signs of ageing of the skin and/or hair, in an animal, preferably the human animal comprising:
applying to the human showing signs of ageing, preferably to the portion of the skin and/or hair showing signs of ageing, a composition comprising one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA at least once a day for a period of time at least sufficient to provide a reduction of the visible signs of ageing, preferably the visible signs of ageing of the skin and/or hair. The period of time at least sufficient to provide the reduction of the visible signs of ageing generally is between one day and 12 months, preferably three days and six months, more preferably between two weeks and two months. A method and/or a composition for reducing stretch marks of the skin, comprising:
applying to the skin, preferably at least to the portion of the skin showing stretchmarks, a composition comprising one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially
FAA at least once a day for a period of time at least sufficient to provide a reduction of the visible signs of stretch marks. The period of time at least sufficient to provide the reduction of the visible signs of stretch marks generally is between one day and 12 months, preferably three days and six months, more preferably between two weeks and two months.
A method and/or a composition for reducing dark circles under the eyes, comprising:
applying to the skin, preferably at least to the portion of the skin showing the dark circles, a composition comprising one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA at least once a day for a period of time at least sufficient to provide a reduction of the dark circles of the portion of human skin. The period of time at least sufficient to provide the reduction of the dark circles generally is between one day and 12 months, preferably three days and six months, more preferably between two weeks and two months.
One aspect of the present invention relates to the use of one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA for the protection of the skin against hair treatment agents, especially for the protection of the skin of the head against pigments, dyestuffs, dyes and/or colouring agents which are commonly used for colouring of the hair. During the treatment of the hair with cosmetic
compositions the contact of the head treatment composition with the underlying skin is normally not completely avoidable. The contact of the head treatment composition with the underlying skin is especially disadvantageous in the case of hair colouring compositions, since the resulting colouration of the parts of the skin around the hair line and/or the roots of the hair is generally regarded as unesthetic and thus undesirous. Thus, it is desirous to protect the skin from the negative effects of the hair treatment compositions. It is known in the art to use a variety compositions, such as emulsions, or other agents, such as vaseline, to achieve such a protection of the skin. However, the compositions and agents of prior art show only limited efficacy and/or have two be removed after the application of the head treatment composition. For example, vaseline is hard to remove from the skin and/or a hair due to its unsolubility in water. For a sufficient removal thereof, the use of strong detergents and/or organic solvents can become necessary, thereby affecting the intended result of the application of the hair treatment composition and/or having negative effect on the condition of the skin and/or hair.
According to the instant invention, one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA can be advantageously applied to protect the skin against hair treatment agents and especially to protect the skin of the head against adverse effects of pigments, dyestuffs, dyes and/or colouring agents, or hair colouring compositions in general.
Thus, a further subject of the instant invention is:
The use of one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA as described above/below for the protection of the skin against hair treatment agents, especially for the protection of the skin of the head against pigments, dyestuffs, dyes and/or colouring agents, or hair colouring compositions in general.
The use of one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA in a composition for the protection of the skin against hair treatment agents, especially for the protection of the skin of the head against pigments, dyestuffs, dyes and/or colouring agents, or hair colouring compositions in general.
The use of one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA for producing a preparation to protect the skin against hair-treatment compositions, preferably compositions which can dye, tint, shape, harden, condition, soften, repair or style hair, and especially compositions which can colour or tint the hair.
The use of one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA for the simultaneous protection of the skin against hair-treatment compositions and additionally for the care of the skin.
The compositions of the invention generally comprise one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA and one or more vehicle or carrier, preferably one or more cosmetically acceptable vehicle or carrier. The one or more vehicles or carriers may be independently selected from the group of hydrophobic and hydrophilic vehicles or carriers. Suitable, hydrophobic vehicles or carriers include, for example, waxy non-ionic substances, preferably waxy non-ionic substances commonly used in cosmetics, including, but not limited to esters and ethers of fatty alcohols and of fatty acids, with carbon chain length from C4 to C22, preferably from C8 to C18, and most preferably from C12 to C18. Examples of a fatty hydrophobic carriers or vehicles are preferably selected from the group consisting of isopropyl myristate, isopropyl palmitate, octyl palmitate, isopropyl lanolate, acetylated lanolin alcohol, the benzoate of C12- C15 alcohols, cetearyl octanoate, cetyl palmitate, myristyl myristate, myristyl lactate, cetyl acetate, propylene glycol dicaprylate/caprate, decyl oleate, acetylated lanolin, stearyl heptanoate, diisostearyl malate, octyl
hydroxystearate, octyl hydroxystearate, and isopropyl isostearate, and the like. Examples of hydrophilic carrier or vehicles, especially for solutions, are preferably selected from the group consisting of glycols and alkoxylated glycols, preferably glycols and alkoxylated glycols commonly used in cosmetics, including, but not limited to, ethylene glycol, diethylene glycol, triethylene glycol, propylene glycol, dipropylene glycol, and the like.
The compositions according to the invention, especially the cosmetic compositions according to the invention may be formulated as creams, lotions, serums, sprays, sticks and other forms known to those skilled in the art. Creams and lotions are the currently preferred product forms. Preferably, the amount typically employed for the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA is from 0.01 to 20% by weight, preferably from 0.1% by weight to 10% by weight and particularly preferably from 1 to 8% by weight.
Preferably, cosmetic compositions can typically comprise the carrier solution described above at levels between about 0.1% and about 90% by weight, preferably between about 1% and about 50%, more preferably between about 1% and about 20%, and more preferred still between about 1% and about 10% by weight.
Optionally, the compositions according to the invention may comprise additional active and inactive ingredients other than FAA derivatives, including, but not limited to, excipients, fillers, emulsifying agents,
antioxidants, surfactants, film formers, chelating agents, gelling agents, thickeners, emollients, humectants, moisturizers, vitamins, minerals, viscosity and/or rheology modifiers, sunscreens, keratolyses, depigmenting agents, retinoids, hormonal compounds, alpha-hydroxy acids, alpha-keto acids, anti- mycobacterial agents, antifungal agents, antimicrobials, antivirals,
analgesics, lipidic compounds, anti- allergenic agents, H1 and/or or H2 antihistamines, anti-inflammatory agents, anti-irritants, antineoplastics, immune system boosting agents, immune system suppressing agents, antiacne agents, anesthetics, antiseptics, insect repellents, skin cooling compounds, skin protectants, skin penetration enhancers, exfollients, lubricants, fragrances, colorants, staining agents, depigmenting agents, hypopigmenting agents, preservatives, stabilizers, pharmaceutical agents, photostabilizing agents, and mixtures thereof. In addition to the foregoing, the personal care products of the invention may contain any other compound for the treatment of skin disorders.
The invention also provides a method for ameliorating and/or preventing signs of human skin photo- and intrinsic aging comprising topically applying the cosmetic compositions of the invention. The cosmetic compositions of the invention are preferably applied to affected skin areas once or twice daily for as long as is necessary to achieve desired anti-aging results. The present invention furthermore relates to compositions, preferably non- therapeutic compositions, comprising one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA and at least one further skin-care ingredient and at least one carrier which is suitable for topical applications, and to the use of the above- mentioned compounds for the care, preservation or improvement of the general state of the skin or hair.
Uses which are preferred in accordance with the invention are, in particular, the use for prophylaxis against time- and/or light-induced ageing processes of the human skin or human hair, in particular for prophylaxis against dry skin, wrinkle formation and/or pigment defects, and/or for the reduction or prevention of the harmful effects of UV rays on the skin, and for prophylaxis against or reduction of skin unevenness, such as wrinkles, fine lines, rough skin or large-pored skin.
Uses which are preferred in accordance with the invention are furthermore the use for the prophylaxis and/or prevention of premature skin ageing, in particular for the prophylaxis and/or prevention of light- or ageing-induced wrinkling of the skin, for the reduction of pigmentation and keratosis actinica, and for the prophylaxis and/or treatment of all diseases which are associated with normal skin ageing or light-induced ageing of the skin, and for the prophylaxis and/or treatment of skin diseases which are associated with defective keratinisation relating to differentiation and cell proliferation, in particular for the treatment of acne vulgaris, acne comedonica, polymorphic acne, acne rosaceae, nodular acne, acne conglobata, age-related acne, acne occuring as a side effect, such as acne Solaris, medicament-related acne or acne professionalis, for the treatment of other defects of
keratinisation, in particular ichthyosis, ichthyosiform states, Darier's disease, keratosis palmoplantaris, leukoplakia, leukoplakiform states, skin and mucosal (buccal) eczema (lichen), for the treatment of other skin diseases which are associated with defective keratinisation and have an inflammatory and/or immunoallergic component, and in particular all forms of psoriasis relating to the skin, mucous membranes and finger- and toenails, and psoriatic rheumatism and skin atopy, such as eczema, or respiratory atopy, or also hypertrophy of the gums, and for the prophylaxis and/or treatment of all benign or malignant excrescence of the dermis or epidermis, which may be of viral origin, such as verruca vulgaris, verruca plana, epidermodysplasia verruciformis, oral papillomatosis, papillomatosis florida, and excrescence which may be caused by UV radiation, in particular epithelioma baso- cellulare and epithelioma spinocellulare.
The present invention also relates to the use of one or more of the
compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA for the preparation of compositions which are suitable for the above-mentioned uses.
The compositions here are preferably non-therapeutical, more preferably either compositions which can be used topically, for example cosmetic or dermatological formulations. In this case, the compositions comprise a cosmetically or dermatologically carrier and, depending on the desired property profile, optionally further suitable ingredients.
The use according to the invention of one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA in compositions offers, inter alia, protection against damage caused directly or indirectly by UV radiation or by processes caused by reactive compounds, such as, for example, skin ageing, loss of skin moisture, loss of skin elasticity, formation of wrinkles or lines or of pigment defects or age spots.
The present invention furthermore relates to the use of the above-mentioned compositions for the prevention of undesired changes in the skin picture, such as, for example, acne or greasy skin, keratoses, light-sensitive, inflammatory, erythematous, allergic or autoimmune-reactive reactions.
However, one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA and compositions according to the invention preferably also serve for calming sensitive and irritated skin, for the preventative regulation of collagen, hyaluronic acid and elastin synthesis, stimulation of DNA synthesis, in particular in the case of deficient or hypoactive skin states, regulation of the transcription and translation of matrix-degrading enzymes, in particular of MMPs, increasing cell
regeneration and regeneration of the skin, increasing the skin's own protective and repair mechanisms for DNA, lipids and/or proteins.
One or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA are typically employed in
accordance with the invention in amounts of from 0.01 to 20% by weight, preferably in amounts of from 0.1% by weight to 10% by weight and particularly preferably in amounts of from 1 to 8% by weight. The person skilled in the art has absolutely no difficulties in selecting the amount correspondingly depending on the intended action of the composition.
In a preferred embodiment of the present invention, at least one further skin- care ingredient is one or more antioxidants and/or vitamins.
There are many proven substances known from the specialist literature which can be used as antioxidants, for example amino acids (for example glycine, histidine, tyrosine, tryptophan) and derivatives thereof, imidazoles (for example urocanic acid) and derivatives thereof, peptides, such as D, L- camosine, D-camosine, L-camosine and derivatives thereof (for example anserine), carotinoids, carotenes (for example α-carotene, β-carotene, lycopene) and derivatives thereof, chlorogenic acid and derivatives thereof, lipoic acid and derivatives thereof (for example dihydrolipoic acid),
aurothioglucose, propylthiouracil and other thiols (for example thioredoxin, glutathione, cysteine, cystine, cystamine and the glycosyl, N-acetyl, methyl, ethyl, propyl, amyl, butyl and lauryl, palmitoyl, oleyl, γ-linoleyl, cholesteryl and glyceryl esters thereof) and salts thereof, dilauryl thiodipropionate, distearyl thiodipropionate, thiodipropionic acid and derivatives thereof (esters, ethers, peptides, lipids, nucleotides, nucleosides and salts), and sulfoximine compounds (for example buthionine sulfoximines, homocysteine sulfoximine, buthionine sulfones, penta-, hexa- and heptathionine sulfoximine) in very low tolerated doses (for example pmol to μmol/kg), furthermore (metal) chelating agents (for example α-hydroxy fatty acids, palmitic acid, phytic acid, lactoferrin), α-hydroxy acids (for example citric acid, lactic acid, malic acid), humic acid, bile acid, bile extracts, bilirubin, biliverdin, EDTA, EGTA and derivatives thereof, unsaturated fatty acids and derivatives thereof, vitamin C and derivatives (for example ascorbyl palmitate, magnesium ascorbyl phosphate, ascorbyl acetate), tocopherols and derivatives (for example vitamin E acetate), and coniferyl benzoate of benzoin resin, rutinic acid and derivatives thereof, α-glycosylrutin, ferulic acid, furfurylideneglucitol, carnosine, butylhydroxytoluene, butylhydroxyanisole, nordihydroguaiaretic acid, trihydroxybutyrophenone, quercetin, uric acid and derivatives thereof, mannose and derivatives thereof, zinc and derivatives thereof (for example ZnO, ZnSO4), selenium and derivatives thereof (for example
selenomethionine), stilbenes and derivatives thereof (for example stilbene oxide, trans-stilbene oxide).
Suitable antioxidants are furthermore described in WO 2006/111233 and WO 2006/111234.
Suitable antioxidants are also compounds of the general formula A and/or B
wherein
R1 is selected from the group consisting of -C(O)CH3, -CO2R3, -C(O)NH2 and
-C(O)N(R4)2,
X is O or NH,
R2 is linear or branched Alkyl having 1 to 30 C-atoms,
R3 is linear or branched Alkyl having 1 to 20 C-atoms,
R4 is in each case independently selected from the group consisting of H and linear or branched Alkyl having 1 to 8 C-atoms,
R5 is selected from the group consisting of linear or branched Alkyl having 1 to 8 C-atoms and linear or branched Alkoxy having 1 to 8 C-atoms and
R6is selected from the group consisting of linear or branched Alkyl mit 1 to 8
C-atoms bedeutet, preferably selected from derivatives of the 2-(4-Hydroxy- 3,5-dimethoxybenzyliden)-malonic acid and/or 2-(4-Hydroxy-3,5- dimethoxybenzyl)-malonic acid , and especially preferably selected from 2-(4- Hydroxy-3,5-dimethoxybenzyliden)-malonic acid-bis-(2-ethylhexyl)ester (z.B. Oxynex® ST Liquid) and/or 2-(4-Hydroxy-3,5-dimethoxybenzyl)-malonic acid- bis-(2-ethylhexyl)ester (z.B. RonaCare® AP).
Mixtures of antioxidants are likewise suitable for use in the cosmetic compositions according to the invention. Known and commercial mixtures are, for example, mixtures comprising, as active ingredients, lecithin, L-(+)-ascorbyl palmitate and citric acid (for example Oxynex® AP), natural tocopherols, L-(+)-ascorbyl palmitate, L-(+)-ascorbic acid and citric acid (for example
Oxynex® K LIQUID), tocopherol extracts from natural sources, L-(+)-ascorbyl palmitate, L-(+)-ascorbic acid and citric acid (for example Oxynex® L
LIQUID), DL-α-tocopherol, L-(+)-ascorbyl palmitate, citric acid and lecithin (for example Oxynex® LM) or butylhydroxytoluene (BHT), L-(+)-ascorbyl palmitate and citric acid (for example Oxynex® 2004). Antioxidants of this type are usually employed with one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA in compositions of this type in ratios in the range from 1000:1 to 1 :1000, preferably in amounts of from 100:1 to 1:100.
The compositions according to the invention may comprise vitamins as further ingredients. The cosmetic compositions according to the invention preferably comprise vitamins and vitamin derivatives selected from vitamin B, thiamine chloride hydrochloride (vitamin B-i), riboflavin (vitamin B2), nicotinamide, vitamin C (ascorbic acid), vitamin D, ergocalciferol (vitamin D2), vitamin E, DL-α-tocopherol, tocopherol E acetate, tocopherol
hydrogensuccinate, vitamin Ki, esculin (vitamin P active ingredient), thiamine (vitamin Bi), nicotinic acid (niacin), pyridoxine, pyridoxal, pyridoxamine (vitamin B6), pantothenic acid, biotin, folic acid and cobalamine (vitamin Bi2), particularly preferably vitamin C and derivatives thereof, DL-α-tocopherol, tocopherol E acetate, nicotinic acid, pantothenic acid and biotin. Vitamins are usually employed here with FAA derivatives, in ratios in the range from 1000:1 to 1 :1000, preferably in amounts of from 100:1 to 1:100. Of the phenols having an antioxidative action, the polyphenols, some of which are naturally occurring, are of particular interest for applications in the pharmaceutical, cosmetic or nutrition sector. For example, the flavonoids or bioflavonoids, which are principally known as plant dyes, frequently have an antioxidant potential. K. Lemanska, H. Szymusiak, B. Tyrakowska,
R. Zielinski, I. M. C. M. Rietjens; Current Topics in Biophysics 2000, 24(2), 101-108, are concerned with effects of the substitution pattern of mono- and dihydroxyflavones. It is observed therein that dihydroxyflavones containing an OH group adjacent to the keto function or OH groups in the 3',4'- or 6,7- or 7,8-position have antioxidative properties, while other mono- and dihydroxyflavones in some cases do not have antioxidative properties.
Quercetin (cyanidanol, cyanidenolon 1522, meletin, sophoretin, ericin, 3,3',4',5,7-pentahydroxyflavone) is frequently mentioned as a particularly effective antioxidant (for example CA. Rice-Evans, N.J. Miller, G. Paganga, Trends in Plant Science 1997, 2(4), 152-159). K. Lemanska, H. Szymusiak, B. Tyrakowska, R. Zielinski, A.E.M.F. Soffers, I. M. C. M. Rietjens; Free Radical Biology&Medicine 2001 , 31(7), 869-881 , have investigated the pH dependence of the antioxidant action of hydroxyflavones. Quercetin exhibits the greatest activity amongst the structures investigated over the entire pH range.
Suitable antioxidants are furthermore compounds of the formula C
where R1 to R10 may be identical or different and are selected from
- H
OR 11
straight-chain or branched d- to C2o-alkyl groups; - straight-chain or branched C3- to C2o-alkenyl groups;
- straight-chain or branched d- to C2o-hydroxyalkyl groups, where the hydroxyl group may be bonded to a primary or secondary carbon atom of the chain and furthermore the alkyl chain may also be interrupted by oxygen and/or
- C3- to C10-cycloalkyl groups and/or C3- to Ci2-cycloalkenyl groups, where the rings may each also be bridged by -(CH2)n- groups, where n = 1 to 3,
- where all OR11 are, independently of one another,
- OH
- straight-chain or branched C1- to C20-alkoxy groups,
- straight-chain or branched C3- to C20-alkenyloxy groups,
- straight-chain or branched Cr to C20-hydroxyalkoxy groups, where the hydroxyl group(s) may be bonded to a primary or secondary carbon atom of the chain and furthermore the alkyl chain may also be interrupted by oxygen, and/or
- C3- to C10-cycloalkoxy groups and/or C3- to Ci2-cycloalkenyloxy groups, where the rings may each also be bridged by -(CH2)n- groups, where n = 1 to 3, and/or
- mono- and/or oligoglycosyl radicals,
with the proviso that at least 4 radicals from R1 to R7 are OH and that the molecule contains at least two pairs of adjacent -OH groups,
- or R2, R5 and R6 are OH and the radicals R1, R3, R4 and R7"10 are H, as described in the earlier German patent application DE 10244282.7. Besides the advantages mentioned above, the advantages of the
compositions according to the invention comprising at least one antioxidant here are, in particular, the antioxidant action and the good skin tolerability. In addition, the compounds of formula C are preferably colourless or have only a weak colour and thus only result in slight discoloration of the compositions, or none at all. It may be also advantageous to administer the compounds of the formula C in encapsulated form, for example as cellulose or chitin capsules, in gelatine or wax matrices or encapsulated with cyclodextrins.
In particular, preferred compositions according to the invention are also suitable for the treatment of skin diseases associated with a defect in keratinisation which affects differentiation and cell proliferation, in particular for the treatment of acne vulgaris, acne comedonica, polymorphic acne, acne rosaceae, nodular acne, acne conglobata, age-induced acne, acne which arises as a side effect, such as acne Solaris, medicament-induced acne or acne professionalis, for the treatment of other defects in keratinisation, in particular ichthyosis, ichthyosiform states, Darier's disease, keratosis palmoplantaris, leucoplasia, leucoplasiform states, herpes of the skin and mucous membrane (buccal) (lichen), for the treatment of other skin diseases associated with a defect in keratinisation and which have an inflammatory and/or immunoallergic component and in particular all forms of psoriasis which affect the skin, mucous membranes and fingers and toenails, and psoriatic rheumatism and skin atopy, such as eczema or respiratory atopy, or hypertrophy of the gums, it furthermore being possible for the compounds to be used for some inflammations which are not associated with a defect in keratinisation, for the treatment of all benign or malignant excrescence of the dermis or epidermis, which may be of viral origin, such as verruca vulgaris, verruca plana, epidermodysplasia verruciformis, oral papillomatosis, papillomatosis florida, and excrescence which may be caused by UV radiation, in particular epithelioma baso-cellulare and epithelioma
spinocellulare, for the treatment of other skin diseases, such as dermatitis bullosa and diseases affecting the collagen, for the treatment of certain eye diseases, in particular corneal diseases, for overcoming or combating light- induced skin ageing associated with ageing, for reducing pigmentation and keratosis actinica and for the treatment of all diseases associated with normal ageing or light-induced ageing, for the prevention or healing of wounds/scars of atrophy of the epidermis and/or dermis caused by locally or systemically applied corticosteroids and all other types of skin atrophy, for the prevention or treatment of defects in wound healing, for the prevention or elimination of stretch marks caused by pregnancy or for the promotion of wound healing, for combating defects in tallow production, such as hyperseborrhoea in acne or simple seborrhoea, for combating or preventing cancer-like states or pre-carcinogenic states, in particular promyelocytic leukaemia, for the treatment of inflammatory diseases, such as arthritis, for the treatment of all virus-induced diseases of the skin or other areas of the body, for the prevention or treatment of alopecia, for the treatment of skin diseases or diseases of other areas of the body with an immunological component, for the treatment of cardiovascular diseases, such as
arteriosclerosis or hypertension, and of non-insulin-dependent diabetes, and for the treatment of skin problems caused by UV radiation.
Compositions which are particularly preferred in accordance with the invention also comprise organic hydrophilic or lipophilic sun-protection filter(s) (UV filters) besides one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, or especially FAA..
These additional UV filters are effective in the UV-A region and/or UV-B region and/or IR and/or VIS region (absorbers). These additional filters can be selected, in particular, from cinnamic acid derivatives, salicylic acid derivatives, camphor derivatives, triazine derivatives, β,β-diphenylacrylate derivatives, p-aminobenzoic acid derivatives and polymeric filters and silicone filters, which are described in the application WO 93/04665. Further examples of organic filters are indicated in the patent application EP-A 0 487 404. The said UV filters are usually named below in accordance with INCI nomenclature.
Particular mention should be made here of: para-aminobenzoic acid and derivatives thereof: PABA, Ethyl PABA, Ethyl dihydroxypropyl PABA, Ethylhexyl dimethyl PABA, for example marketed under the name "Escalol 507" by ISP, Glyceryl PABA, PEG- 25 PABA, for example marketed under the name "Uvinul P25" by
BASF.
Salicylates: homosalate marketed under the name "Eusolex HMS" by Merck; ethylhexyl salicylate, for example marketed under the name "Neo Heliopan OS" by Haarmann and Reirner, dipropylene glycol salicylate, for example marketed under the name "Dipsal" by Scher, TEA salicylate, for example marketed under the name "Neo Heliopan TS" by Haarmann and Reimer. β,β-Diphenylacrylate derivatives: octocrylene, for example marketed under 10 the name "Uvinul N539" by BASF, etocrylene, for example marketed under the name "Uvinul N35" by BASF.
Benzophenone derivatives: benzophenone-1 , for example marketed under the name "Uvinul 400"; benzophenone-2, for example marketed under the name "Uvinul D50"; benzophenone-3 or oxybenzone, for example marketed 15 under the name "Uvinul M40"; benzophenone-4, for example marketed under the name "Uvinul MS40"; benzophenone-9, for example marketed under the name "Uvinul DS-49" by BASF, benzophenone-5, benzophenone-6, for example marketed under the name "Helisorb 11" by Norquay,
benzophenone-8, for example marketed under the name "Spectra-Sorb UV-
24" by American Cyanamid, benzophenone-12 n-hexyl 2-(4-diethylamino-2-
20
hydroxybenzoyl)benzoate.
Benzylidenecamphor derivatives: 3-benzylidenecamphor, for example marketed under the name "Mexoryl SD" by Chimex, 4-methylbenzylidene- camphor, for example marketed under the name "Eusolex 6300" by Merck, pj. benzylidenecamphorsulfonic acid, for example marketed under the name
"Mexoryl SL" by Chimex, camphor benzalkonium methosulfate, for example marketed under the name "Mexoryl SO" by Chimex, terephthalylidene- dicamphorsulfonic acid, for example marketed under the name "Mexoryl SX" by Chimex, polyacrylamidomethylbenzylidenecamphor marketed under the name "Mexoryl SW" by Chimex.
30
Phenylbenzimidazole derivatives: phenylbenzimidazolesulfonic acid, for example marketed under the name "Eusolex 232" by Merck, disodium phenyl dibenzimidazole tetrasulfonate, for example marketed under the name "Neo Heliopan AP" by Haarmann and Reimer.
Phenylbenzotriazole derivatives: drometrizole trisiloxane, for example mar- keted under the name "Silatrizole" by Rhodia Chimie, methylenebis(benzo- triazolyl)tetramethylbutylphenol in solid form, for example marketed under the name "MIXXIM BB/100" by Fairmount Chemical, or in micronised form as an aqueous dispersion, for example marketed under the name "Tinosorb M" by Ciba Specialty Chemicals. Triazine derivatives: ethylhexyltriazone, for example marketed under the name "Uvinul T150" by BASF, diethylhexylbutamidotriazone, for example marketed under the name "Uvasorb HEB" by Sigma 3V, 2,4,6-tris(diisobutyl- 4'-aminobenzalmalonate)-s-triazine.
Anthraniline derivatives: menthyl anthranilate, for example marketed under the name "Neo Heliopan MA" by Haarmann and Reimer.
Imidazole derivatives: ethylhexyldimethoxybenzylidenedioxoimidazoline propionate.
Benzalmalonate derivatives: polyorganosiloxanes containing functional benzalmalonate groups, such as, for example, polysilicone-15, for example marketed under the name "Parsol SLX" by Hoffmann LaRoche.
4,4-Diarylbutadiene derivatives: 1 ,1-dicarboxy(2,2'-dimethylpropyl)-4,4- diphenylbutadiene.
Benzoxazole derivatives: 2,4-bis[5-(1-dimethylpropyl)benzoxazol-2-yl(4- phenyl)imino]-6-(2-ethylhexyl)imino-1 ,3,5-triazine, for example marketed under the name Uvasorb K2A by Sigma 3V, and mixtures comprising this.
Piperazinderivatives such as the compound
The compounds listed should only be regarded as examples. It is of course also possible to use other L)V filters. In particular, organic particulate UV filters, as described, for example, in the patent application WO 99/66896, can advantageously also be combined with the particulate UV protection agents according to the invention.
The organic UV-protecting substances which are suitable for combination with the UV protection agent according to the invention can preferably be selected from the following list: Ethylhexyl salicylate, Octocrylene, Butyl- methoxydibenzoylmethane, Phenylbenzimidazolesulfonic acid, Benzo- phenone-3, Benzophenone-4, Benzophenone-5, n-Hexyl 2-(4-diethylamino- 2-hydroxybenzoyl)benzoate, 4-Methylbenzylidenecamphor, Terephthalyli- denedicamphorsulfonic acid, Disodium phenyldibenzimidazoletetrasulfonate, Methylenebis(benzotriazolyl)tetramethylbutylphenol, Ethylhexyl Triazone, Diethylhexyl Butamido Triazone, Drometrizole trisiloxane, Polysilicone-15, 1 ,1-Dicarboxy(2,2'-dimethylpropyl)-4,4-diphenylbutadiene, 2,4-Bis[5-(1- dimethylpropyl)benzoxazol-2-yl(4-phenyl) imino]-6-(2-ethylhexyl)imino-1 ,3,5- triazine and mixtures thereof.
These organic UV filters are generally incorporated into cosmetic formulations in an amount of 0.01 to 20 per cent by weight, preferably 1-10% by weight.
Organic UV filters are generally incorporated into cosmetic formulations in a total amount of 0.01 to 20 per cent by weight, preferably 0.5-20%. Compositions which are particularly preferred in accordance with the invention may also comprise inorganic sun-protection filter(s) (particulate UV filters) besides one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, or especially FAA.
Particulate UV filters may be comprised both as powder and also as dispersion or paste. Preference is given here both to those from the group of the titanium dioxides, such as, for example, coated titanium dioxide (for example
Eusolex® T-2000, Eusolex®T-AQUA, Eusolex®T-AVO, Eusolex®T-OLEO), zinc oxides (for example Sachtotec®), iron oxides or also cerium oxides and/or zirconium oxides. Furthermore, combinations with pigmentary titanium dioxide or zinc oxide are also possible, where the particle size of these pigments is greater than or equal to 200 nm, for example Hombitec® COS.
It may furthermore be preferred in accordance with the invention for the compositions to comprise inorganic UV filters which have been aftertreated by conventional methods, as described, for example, in Cosmetics &
Toiletries, February 1990, Vol. 105, pp. 53-64. One or more of the following aftertreatment components can be selected here: amino acids, beeswax, fatty acids, fatty acid alcohols, anionic surfactants, lecithin, phospholipids, sodium, potassium, zinc, iron or aluminium salts of fatty acids, polyethylenes, silicones, proteins (particularly collagen or elastin), alkanolamines, silicon dioxide, aluminium oxide, further metal oxides, phosphates, such as sodium hexametaphosphate, or glycerin.
Further particulate UV filters which are preferably employed here are: - untreated titanium dioxides, such as, for example, the products Micro- titanium Dioxide MT 500 B from Tayca; titanium dioxide P25 from Degussa, aftertreated micronised titanium dioxides with aluminium oxide and silicon dioxide aftertreatment, such as, for example, the product "Microtitanium Dioxide MT 100 SA" from Tayca; or the product "Tioveil Fin" from Uniqema,
5 - aftertreated micronised titanium dioxides with aluminium oxide and/or aluminium stearate/laurate aftertreatment, such as, for example, Microtitanium Dioxide MT 100 T from Tayca, Eusolex T-2000 from Merck,
aftertreated micronised titanium dioxides with iron oxide and/or iron stearate aftertreatment, such as, for example, the product "Microtitanium Dioxide MT 100 F" from Tayca,
aftertreated micronised titanium dioxides with silicon dioxide, aluminium oxide and silicone aftertreatment, such as, for example, the product "Microtitanium Dioxide MT 100 SAS" from Tayca,
aftertreated micronised titanium dioxides with sodium hexametaphos- phates, such as, for example, the product "Microtitanium Dioxide MT 150 W" from Tayca.
The treated micronised titanium dioxides employed for the combination may also be aftertreated with:
20
octyltrimethoxysilanes; such as, for example, the product Tego Sun T
805 from Degussa,
silicon dioxide; such as, for example, the product Parsol T-X from DSM, aluminium oxide and stearic acid; such as, for example, the product UV- ?J- Titan M160 from Kemira,
aluminium and glycerin; such as, for example, the product UV-Titan from Kemira,
aluminium and silicone oils, such as, for example, the product UV-Titan M262 from Kemira,
30 - sodium hexametaphosphate and polyvinylpyrrolidone,
polydimethylsiloxanes, such as, for example, the product 70250 Cardre UF TiO2SI3 from Cardre, polydimethylhydrogenosiloxanes, such as, for example, the product Microtitanium Dioxide USP Grade Hydrophobic from Color Techniques.
The combination with the following products may furthermore also be advantageous: untreated zinc oxides, such as, for example, the product Z-Cote from BASF (Sunsmart), Nanox from Elementis
aftertreated zinc oxides, such as, for example, the following products: o "Zinc Oxide CS-5" from Toshibi (ZnO aftertreated with polymethyl- hydrogenosiloxanes)
o Nanogard Zinc Oxide FN from Nanophase Technologies
o "SPD-Z1" from Shin-Etsu (ZnO aftertreated with a silicone-grafted acrylic polymer, dispersed in cyclodimethylsiloxanes)
o "Escalol Z100" from ISP (aluminium oxide-aftertreated ZnO dispersed in an ethylhexyl methoxycinnamate/PVP-hexadecene/- methicone copolymer mixture)
o "Fuji ZNO-SMS-10" from Fuji Pigment (ZnO aftertreated with silicon dioxide and polymethylsilesquioxane)
o untreated cerium oxide micropigment, for example with the name
"Colloidal Cerium Oxide" from Rhone Poulenc
o untreated and/or aftertreated iron oxides with the name Nanogar from Arnaud. For example, it is also possible to employ mixtures of various metal oxides, such as, for example, titanium dioxide and cerium oxide, with and without aftertreatment, such as, for example, the product Sunveil A from Ikeda. In addition, it is also possible to use mixtures of aluminium oxide, silicon dioxide and silicone-aftertreated titanium dioxide, zinc oxide mixtures, such as, for example, the product UV-Titan M261 from Kemira, in combination with the UV protection agent according to the invention.
These inorganic UV filters are generally incorporated into cosmetic compositions in an amount of 0.1 to 25 per cent by weight, preferably 2-10%. In particular, it may be preferred here for a nanoparticulate UV protection agent according to the invention to be present in one phase in emulsions and a further inorganic UV filter to be present in the other phase. Through combination of one or more of the compounds according to formula
(I), preferably FAA and/or its derivatives, and especially FAA with further UV filters, the protective action against harmful influences of UV radiation can be optimised.
All the said UV filters can also be employed in encapsulated form. In particular, it is advantageous to employ organic UV filters in encapsulated form. In detail, the following advantages arise:
- The hydrophilicity of the capsule wall can be set independently of the solubility of the UV filter. Thus, for example, it is also possible to incorporate hydrophobic UV filters into purely aqueous compositions. In addition, the oily impression on application of the composition comprising hydrophobic UV filters, which is frequently regarded as unpleasant, is suppressed.
- Certain UV filters, in particular dibenzoylmethane derivatives, exhibit only reduced photostability in cosmetic compositions. Encapsulation of these filters or compounds which impair the photostability of these filters, such as, for example, cinnamic acid derivatives, enables the photostability of the entire composition to be increased.
- Skin penetration by organic UV filters and the associated potential for irritation on direct application to the human skin is repeatedly being
discussed in the literature. The encapsulation of the corresponding
substances which is proposed here suppresses this effect.
- In general, encapsulation of individual UV filters or other ingredients enables composition problems caused by the interaction of individual composition constituents with one another, such as crystallisation processes, precipitation and agglomerate formation, to be avoided since the interaction is suppressed.
It is therefore preferred in accordance with the invention for one or more of the above-mentioned UV filters to be in encapsulated form. It is advantageous here for the capsules to be so small that they cannot be viewed with the naked eye. In order to achieve the above-mentioned effects, it is furthermore necessary for the capsules to be sufficiently stable and the encapsulated active ingredient (UV filter) only to be released to the environ- ment to a small extent, or not at all.
Suitable capsules can have walls of inorganic or organic polymers. For example, US 6,242,099 B1 describes the production of suitable capsules with walls of chitin, chitin derivatives or polyhydroxylated polyamines. Capsules which can particularly preferably be employed in accordance with the invention have walls which can be obtained by a sol-gel process, as described in the applications WO 00/09652, WO 00/72806 and
WO 00/71084. Preference is again given here to capsules whose walls are built up from silica gel (silica; undefined silicon oxide hydroxide). The production of corresponding capsules is known to the person skilled in the art, for example from the cited patent applications, whose contents expressly also belong to the subject-matter of the present application.
The capsules are preferably present in compositions according to the invention in amounts which ensure that the encapsulated UV filters are present in the composition in the above-indicated amounts.
The skin-protecting or skin-care active ingredients can in principle be any active ingredients known to the person skilled in the art.
In an embodiment of the present invention, particularly preferred active ingredients are pyrimidinecarboxylic acids and/or aryl oximes.
Pyrimidinecarboxylic acids occur in halophilic microorganisms and play a role in osmoregulation of these organisms (E.A. Galinski et al., Eur. J. Biochem., 149 (1985) pages 135-139). Of the pyrimidinecarboxylic acids, particular mention should be made here of ectoine ((S)-1 ,4,5,6-tetrahydro-2-methyl-4- pyrimidinecarboxylic acid) and hydroxyectoine ((S1S)-1 ,4,5,6-tetrahydro-5- hydroxy-2-methyl-4-pyrimidinecarboxylic acid) and derivatives thereof. These compounds stabilise enzymes and other biomolecules in aqueous solutions and organic solvents. Furthermore, they stabilise, in particular, enzymes against denaturing conditions, such as salts, extreme pH values, surfactants, urea, guanidinium chloride and other compounds.
Ectoine and ectoine derivatives, such as hydroxyectoine, can
advantageously be used in medicaments. In particular, hydroxyectoine can be employed for the preparation of a medicament for the treatment of skin diseases.
Of the cosmetic applications, particular mention should be made of the use of ectoine and ectoine derivatives for the care of aged, dry or irritated skin.
Thus, European patent application EP-A-O 671 161 describes, in particular, that ectoine and hydroxyectoine are employed in cosmetic compositions, such as powders, soaps, surfactant-containing cleansing products, lipsticks, rouge, make-ups, care creams and sunscreen compositions.
Preference is given here to the use of a pyrimidinecarboxylic acid of the following formula
in which
R1 is a radical H or C1-8-alkyl,
R2 is a radical H or C1-4-alkyl,
and R3, R4, R5 and R6
are each, independently of one another, a radical from the group consisting of H, OH, NH2 and C1-4-alkyl. Preference is given to the use of pyrimidinecarboxylic acids in which R2 is a methyl or ethyl group, and R1 or R5 and R6 are H.
Particular preference is given to the use of the pyrimidinecarboxylic acids ectoine ((S)-1 ,4,5,6-tetrahydro-2-methyl-4-pyrimidinecarboxylic acid) and hydroxyectoine ((S1S)-1 ,4, 5,6-tetrahydro-5-hydroxy-2-methyl-4-pyrimidine- carboxylic acid). The compositions according to the invention preferably comprise pyrimidinecarboxylic acids of this type in amounts of up to 15% by weight. The pyrimidinecarboxylic acids are preferably employed here in ratios of from 100:1 to 1 :100 with respect to one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA with ratios in the range from 1 :10 to 10:1 being particularly preferred.
Of the aryl oximes, preference is given to the use of 2-hydroxy-5-methyllauro- phenone oxime, which is also known as HMLO, LPO or F5. Its suitability for use in cosmetic compositions is disclosed, for example, in DE-A-41 16 123. Compositions which comprise 2-hydroxy-5-methyllaurophenone oxime are accordingly suitable for the treatment of skin diseases which are
accompanied by inflammation. It is known that compositions of this type can be used, for example, for the therapy of psoriasis, various forms of eczema, irritative and toxic dermatitis, UV dermatitis and further allergic and/or inflammatory diseases of the skin and integumentary appendages.
Compositions according to the invention which, in addition to one or more of the compounds according to formula (I), preferably FAA and/or its
derivatives, and especially FAA additionally comprise an aryl oxime, preferably 2-hydroxy-5-methyllaurophenone oxime, exhibit surprising antiinflammatory suitability. The compositions here preferably comprise from 0.01 to 10% by weight of the aryl oxime, it being particularly preferred for the composition to comprise from 0.05 to 5% by weight of aryl oxime.
All compounds or components which can be used in the compositions are either known or commercially available or can be synthesised by known processes. The preparation of one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA is described in one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA can be incorporated into cosmetic or dermatological compositions in the customary manner. Suitable
compositions are for example in the form of a cream, lotion or gel or as a solution which can be sprayed onto the skin. Use forms of the compositions according to the invention that may be mentioned are, for example, solutions, suspensions, emulsions, PIT emulsions, pastes, ointments, gels, creams, lotions, powders, soaps, surfactant-containing cleansing preparations, oils, aerosols and sprays.
Examples of other use forms are sticks, shampoos and shower compositions.
Any desired customary carriers, assistants and, if desired, further active ingredients may be added to the composition.
Preferred assistants originate from the group consisting of preservatives, antioxidants, stabilisers, solubilisers, vitamins, colorants and odour im- provers.
Ointments, pastes, creams and gels may comprise the customary carriers, for example 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 may comprise the customary carriers, for example lactose, talc, silica, aluminium hydroxide, calcium silicate and polyamide powder, or mixtures of these substances. Sprays may additionally comprise the customary propellants, for example chlorofluorocarbons, propane/butane or dimethyl ether.
Solutions and emulsions may comprise the customary carriers, such as solvents, solubilisers and emulsifiers, for example water, ethanol,
isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyl glycol, oils, in particular cottonseed oil, peanut oil, wheatgerm oil, olive oil, castor oil and sesame oil, glycerol fatty acid esters, polyethylene glycols and fatty acid esters of sorbitan, or mixtures of these substances.
Suspensions may comprise the customary carriers, such as liquid diluents, for example water, ethanol or propylene glycol, suspending agents, for example ethoxylated isostearyl alcohols, polyoxyethylene sorbitol esters and polyoxyethylene sorbitan esters, microcrystalline cellulose, aluminium metahydroxide, bentonite, agar-agar and tragacanth, or mixtures of these substances. Soaps may comprise the customary carriers, such as alkali metal salts of fatty acids, salts of fatty acid monoesters, fatty acid protein hydrolysates, isethionates, lanolin, fatty alcohol, vegetable oils, plant extracts, glycerol, sugars, or mixtures of these substances.
Surfactant-containing cleansing products may comprise the customary carriers, such as salts of fatty alcohol sulfates, fatty alcohol ether sulfates, sulfosuccinic acid monoesters, fatty acid protein hydrolysates, isothionates, imidazolinium derivatives, methyl taurates, sarcosinates, fatty acid amide ether sulfates, alkylamidobetaines, fatty alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable and synthetic oils, lanolin derivatives, ethoxylated glycerol fatty acid esters, or mixtures of these substances.
Face and body oils may comprise the customary carriers, such as synthetic oils, such as fatty acid esters, fatty alcohols, silicone oils, natural oils, such as vegetable oils and oily plant extracts, paraffin oils or lanolin oils, or mixtures of these substances.
Further typical cosmetic use forms are also lipsticks, lip-care sticks, mascara, eyeliner, eye-shadow, rouge, powder make-up, emulsion make-up and wax make-up, and sunscreen, pre-sun and after-sun preparations.
The preferred composition forms according to the invention include, in par- ticular, emulsions.
Emulsions according to the invention are advantageous and comprise, for example, the fats, oils, waxes and other fatty substances, as well as water and an emulsifier, as usually used for a composition of this type.
The lipid phase may advantageously be selected from the following group of substances:
- mineral oils, mineral waxes;
- oils, such as triglycerides of capric or caprylic acid, furthermore natural oils, such as, for example, castor oil;
- fats, waxes and other natural and synthetic fatty substances, preferably esters of fatty acids with alcohols having a low carbon number, for example with isopropanol, propylene glycol or glycerol, or esters of fatty alcohols with alkanoic acids having a low carbon number or with fatty acids; - silicone oils, such as dimethylpolysiloxanes, diethylpolysiloxanes, diphenylpolysiloxanes and mixed forms thereof.
For the purposes of the present invention, the oil phase of the emulsions, oleogels or hydrodispersions or lipodispersions is advantageously selected from the group consisting of esters of saturated and/or unsaturated, branched and/or unbranched alkanecarboxylic acids having a chain length of from 3 to 30 carbon atoms and saturated and/or unsaturated, branched and/or unbranched alcohols having a chain length of from 3 to 30 carbon atoms, or from the group consisting of esters of aromatic carboxylic acids and saturated and/or unsaturated, branched and/or unbranched alcohols having a chain length of from 3 to 30 carbon atoms. Ester oils of this type can then advantageously be selected from the group consisting of isopropyl myristate, isopropyl palmitate, isopropyl stearate, isopropyl oleate, n-butyl stearate, n-hexyl laurate, n-decyl oleate, isooctyl stearate, isononyl stearate, isononyl isononanoate, 2-ethylhexyl palmitate, 2-ethylhexyl laurate,
2-hexyldecyl stearate, 2-octyldodecyl palmitate, oleyl oleate, oleyl erucate, erucyl oleate, erucyl erucate and synthetic, semi-synthetic and natural mixtures of esters of this type, for example jojoba oil.
The oil phase may furthermore advantageously be selected from the group consisting of branched and unbranched hydrocarbons and waxes, silicone oils, dialkyl ethers, or the group consisting of saturated and unsaturated, branched and unbranched alcohols, and fatty acid triglycerides, specifically the triglycerol esters of saturated and/or unsaturated, branched and/or unbranched alkanecarboxylic acids having a chain length of from 8 to 24, in particular 12-18, carbon atoms. The fatty acid triglycerides may
advantageously be selected, for example, from the group consisting of synthetic, semi-synthetic and natural oils, for example olive oil, sunflower oil, soya oil, peanut oil, rapeseed oil, almond oil, palm oil, coconut oil, palm kernel oil and the like.
Any desired mixtures of oil and wax components of this type may also advantageously be employed for the purposes of the present invention. It may also be advantageous to employ waxes, for example cetyl palmitate, as the only lipid component of the oil phase.
The oil phase is advantageously selected from the group consisting of 2-ethylhexyl isostearate, octyldodecanol, isotridecyl isononanoate, iso- eicosane, 2-ethylhexyl cocoate, benzoate, caprylic/capric acid triglyceride and dicapryl ether.
Particularly advantageous are mixtures of Ci2-is-alkyl benzoate and 2- ethylhexyl isostearate, mixtures of Ci2-i5-alkyl benzoate and isotridecyl isononanoate, as well as mixtures of Ci2-i5-alkyl benzoate, 2-ethylhexyl isostearate and isotridecyl isononanoate.
Of the hydrocarbons, paraffin oil, squalane and squalene may
advantageously be used for the purposes of the present invention.
Furthermore, the oil phase may also advantageously have a content of cyclic or linear silicone oils or consist entirely of oils of this type, although it is preferred to use an additional content of other oil-phase components in addition to the silicone oil or the silicone oils.
The silicone oil to be used in accordance with the invention is advantageously cyclomethicone (octamethylcyclotetrasiloxane). However, it is also advantageous for the purposes of the present invention to use other silicone oils, for example hexamethylcyclotrisiloxane, polydimethylsiloxane or poly(methylphenylsiloxane).
Also particularly advantageous are mixtures of cyclomethicone and isotridecyl isononanoate and of cyclomethicone and 2-ethylhexyl isostearate. The aqueous phase of the compositions according to the invention optionally advantageously comprises alcohols, diols or polyols having a low carbon number, and ethers thereof, preferably ethanol, isopropanol, propylene glycol, glycerol, ethylene glycol, ethylene glycol monoethyl or monobutyl ether, propylene glycol monomethyl, monoethyl or monobutyl ether, diethylene glycol monomethyl or monoethyl ether and analogous products, furthermore alcohols having a low carbon number, for example ethanol, isopropanol, 1 ,2-propanediol or glycerol, and, in particular, one or more thickeners, which may advantageously be selected from the group consisting of silicon dioxide, aluminium silicates, polysaccharides and derivatives thereof, for example hyaluronic acid, xanthan gum,
hydroxypropylmethylcellulose, particularly advantageously from the group consisting of the polyacrylates, preferably a polyacrylate from the group consisting of the so-called Carbopols, for example Carbopol grades 980, 981 ,
1382, 2984 or 5984, in each case individually or in combination.
In particular, mixtures of the above-mentioned solvents are used. In the case of alcoholic solvents, water may be a further constituent.
In a preferred embodiment, the compositions according to the invention comprise hydrophilic surfactants.
The hydrophilic surfactants are preferably selected from the group consisting of the alkylglucosides, acyllactylates, betaines and coconut amphoacetates.
Alkylglycosides which are particularly advantageously used for the purposes of the invention are selected from the group consisting of octyl
glucopyranoside, nonyl glucopyranoside, decyl glucopyranoside, undecyl glucopyranoside, dodecyl glucopyranoside, tetradecyl glucopyranoside and hexadecyl glucopyranoside.
It is likewise advantageous to employ natural or synthetic raw materials and assistants or mixtures which are distinguished by an effective content of the active ingredients used in accordance with the invention, for example
Plantaren® 1200 (Henkel KGaA), Oramix® NS 10 (Seppic).
In addition, sodium isostearyl lactylate, for example the product Pathionic®
ISL from the American Ingredients Company, is advantageous.
The betaines are advantageously selected from the group consisting of the substances which are distinguished by the structural formulae
where R2 is a branched or unbranched alkyl radical having from 1 to 30 carbon atoms.
R2 is particularly advantageously a branched or unbranched alkyl radical having from 6 to 12 carbon atoms.
For example, capramidopropylbetaine, for example the product Tego® Betain 810 from Th. Goldschmidt AG1 is advantageous.
A coconut amphoacetate which is advantageous for the purposes of the invention is, for example, sodium coconut amphoacetate, as available under the name Miranol® Ultra C32 from Miranol Chemical Corp.
The compositions according to the invention are advantageously
characterised in that the hydrophilic surfactant(s) is (are) present in concentrations of 0.01-20% by weight, preferably 0.05-10% by weight, particularly preferably 0.1-5% by weight, in each case based on the total weight of the composition.
For use, the cosmetic and dermatological compositions are applied in sufficient amount to the skin and/or hair in the usual manner for cosmetics. Cosmetic and dermatological compositions according to the invention may exist in various forms. Thus, they may be, for example, a solution, a water- free composition, an emulsion or microemulsion of the water-in-oil (W/O) or oil-in-water (O/W) type, a multiple emulsion, for example of the water-in-oil- in-water (W/O/W) type, a gel, a solid stick, an ointment or an aerosol. It is also advantageous to administer ectoines in encapsulated form, for example in collagen matrices and other conventional encapsulation materials, for example as cellulose encapsulations, in gelatine, wax matrices or liposomally encapsulated. In particular, wax matrices, as described in DE-A 43 08 282, have proven favourable. Preference is given to emulsions. O/W emulsions are particularly preferred. Emulsions, W/O emulsions and O/W emulsions are obtainable in a conventional manner.
Emulsifiers that can be used are, for example, the known W/O and O/W emulsifiers. It is advantageous to use further conventional co-emulsifiers in the preferred O/W emulsions according to the invention. Co-emulsifiers which are advantageous according to the invention are, for example, O/W emulsifiers, principally from the group consisting of the substances having HLB values of 11-16, very particularly advantageously having HLB values of 14.5-15.5, so long as the O/W emulsifiers have saturated radicals R and R'. If the O/W emulsifiers have unsaturated radicals R and/or
R1 or in the case of isoalkyl derivatives, the preferred HLB value of such emulsifiers may also be lower or higher.
It is advantageous to select the fatty alcohol ethoxylates from the group consisting of ethoxylated stearyl alcohols, cetyl alcohols, cetylstearyl alcohols (cetearyl alcohols). Particular preference is given to the following:
polyethylene glycol (13) stearyl ether (steareth-13), polyethylene glycol (14) stearyl ether (steareth-14), polyethylene glycol (15) stearyl ether (steareth- 15), polyethylene glycol (16) stearyl ether (steareth-16), polyethylene glycol (17) stearyl ether (steareth-17), polyethylene glycol (18) stearyl ether
(steareth-18), polyethylene glycol (19) stearyl ether (steareth-19),
polyethylene glycol (20) stearyl ether (steareth-20), polyethylene glycol (12) isostearyl ether (isosteareth-12), polyethylene glycol (13) isostearyl ether (isosteareth-13), polyethylene glycol (14) isostearyl ether (isosteareth-14), polyethylene glycol (15) isostearyl ether (isosteareth-15), polyethylene glycol (16) isostearyl ether (isosteareth-16), polyethylene glycol (17) isostearyl ether (isosteareth-17), polyethylene glycol (18) isostearyl ether (isosteareth-18), polyethylene glycol (19) isostearyl ether (isosteareth-19), polyethylene glycol (20) isostearyl ether (isosteareth-20), polyethylene glycol (13) cetyl ether (ceteth-13), polyethylene glycol (14) cetyl ether (ceteth-14), polyethylene glycol (15) cetyl ether (ceteth-15), polyethylene glycol (16) cetyl ether (ceteth- 16), polyethylene glycol (17) cetyl ether (ceteth-17), polyethylene glycol (18) cetyl ether (ceteth-18), polyethylene glycol (19) cetyl ether (ceteth-19), polyethylene glycol (20) cetyl ether (ceteth-20), polyethylene glycol (13) isocetyl ether (isoceteth-13), polyethylene glycol (14) isocetyl ether
(isoceteth-14), polyethylene glycol (15) isocetyl ether (isoceteth-15), polyethylene glycol (16) isocetyl ether (isoceteth-16), polyethylene glycol (17) isocetyl ether (isoceteth-17), polyethylene glycol (18) isocetyl ether (isoceteth-18), polyethylene glycol (19) isocetyl ether (isoceteth-19), polyethylene glycol (20) isocetyl ether (isoceteth-20), polyethylene glycol (12) oleyl ether (oleth-12), polyethylene glycol (13) oleyl ether (oleth-13), polyethylene glycol (14) oleyl ether (oleth-14), polyethylene glycol (15) oleyl ether (oleth-15), polyethylene glycol (12) lauryl ether (laureth-12), polyethylene glycol (12) isolauryl ether (isolaureth-12), polyethylene glycol (13) cetylstearyl ether (ceteareth-13), polyethylene glycol (14) cetylstearyl ether (ceteareth- 14), polyethylene glycol (15) cetylstearyl ether (ceteareth-15), polyethylene glycol (16) cetylstearyl ether (ceteareth-16), polyethylene glycol (17) cetylstearyl ether (ceteareth-17), polyethylene glycol (18) cetylstearyl ether (ceteareth-18), polyethylene glycol (19) cetylstearyl ether (ceteareth-19), polyethylene glycol (20) cetylstearyl ether (ceteareth-20).
An ethoxylated alkyl ether carboxylic acid or salt thereof which can
advantageously be used is sodium laureth-11 carboxylate. An alkyl ether sulfate which can advantageously be used is sodium laureth-14 sulfate. An ethoxylated cholesterol derivative which can advantageously be used is polyethylene glycol (30) cholesteryl ether. Polyethylene glycol (25) soyasterol has also proven successful. Ethoxylated triglycerides which can
advantageously be used are the polyethylene glycol (60) evening primrose glycerides.
It is furthermore advantageous to select the polyethylene glycol glycerol fatty acid esters from the group consisting of polyethylene glycol (20) glyceryl laurate, polyethylene glycol (21) glyceryl laurate, polyethylene glycol (22) glyceryl laurate, polyethylene glycol (23) glyceryl laurate, polyethylene glycol (6) glyceryl caprate/caprinate, polyethylene glycol (20) glyceryl oleate, polyethylene glycol (20) glyceryl isostearate, polyethylene glycol (18) glyceryl oleate/cocoate.
It is likewise favourable to select the sorbitan esters from the group
consisting of polyethylene glycol (20) sorbitan monolaurate, polyethylene glycol (20) sorbitan monostearate, polyethylene glycol (20) sorbitan
monoisostearate, polyethylene glycol (20) sorbitan monopalmitate,
polyethylene glycol (20) sorbitan monooleate. Optional W/O emulsifiers, but ones which may nevertheless be
advantageous for the purposes of the invention can be the following:
fatty alcohols having from 8 to 30 carbon atoms, monoglycerol esters of saturated and/or unsaturated, branched and/or unbranched alkanecarboxylic acids having a chain length of from 8 to 24 carbon atoms, in particular 12-18 carbon atoms, diglycerol esters of saturated and/or unsaturated, branched and/or unbranched alkanecarboxylic acids having a chain length of from 8 to 24 carbon atoms, in particular 12-18 carbon atoms, monoglycerol ethers of saturated and/or unsaturated, branched and/or unbranched alcohols having a chain length of from 8 to 24 carbon atoms, in particular 12-18 carbon atoms, diglycerol ethers of saturated and/or unsaturated, branched and/or unbranched alcohols having a chain length of from 8 to 24 carbon atoms, in particular 12-18 carbon atoms, propylene glycol esters of saturated and/or unsaturated, branched and/or unbranched alkanecarboxylic acids having a chain length of from 8 to 24 carbon atoms, in particular 12-18 carbon atoms, and sorbitan esters of saturated and/or unsaturated, branched and/or unbranched alkanecarboxylic acids having a chain length of from 8 to 24 carbon atoms, in particular 12-18 carbon atoms.
Particularly advantageous W/O emulsifiers are glyceryl monostearate, glyceryl monoisostearate, glyceryl monomyristate, glyceryl monooleate, diglyceryl monostearate, diglyceryl monoisostearate, propylene glycol monostearate, propylene glycol monoisostearate, propylene glycol monocaprylate, propylene glycol monolaurate, sorbitan monoisostearate, sorbitan monolaurate, sorbitan monocaprylate, sorbitan monoisooleate, sucrose distearate, cetyl alcohol, stearyl alcohol, arachidyl alcohol, behenyl alcohol, isobehenyl alcohol, selachyl alcohol, chimyl alcohol, polyethylene glycol (2) stearyl ether (steareth-2), glyceryl monolaurate, glyceryl mono- caprinate and glyceryl monocaprylate.
Preferred compositions according to the invention are particularly suitable for protecting human skin against ageing processes and against oxidative stress, i.e. against damage by free radicals, as are produced, for example, by sunlight, heat or other influences. In this connection, they are in the various administration forms usually used for this application. For example, they may, in particular, be in the form of a lotion or emulsion, such as in the form of a cream or milk (O/W, W/O, OΛ/V/0, W/OΛ/V), in the form of oily-alcoholic, oily- aqueous or aqueous-alcoholic gels or solutions, in the form of solid sticks or may be formulated as an aerosol.
The composition may comprise cosmetic adjuvants which are usually used in this type of composition, such as, for example, thickeners, softeners, moisturisers, surfactants, emulsifiers, preservatives, antifoams, perfumes, waxes, lanolin, propellants, dyes and/or pigments which colour the
composition itself or the skin, and other ingredients usually used in
cosmetics.
The dispersant or solubiliser used can be an oil, wax or other fatty substance, a lower monoalcohol or lower polyol or mixtures thereof. Particularly preferred monoalcohols or polyols include ethanol, isopropanol, propylene glycol, glycerol and sorbitol.
A preferred embodiment of the invention is an emulsion in the form of a protective cream or milk which, apart from one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA comprises, for example, fatty alcohols, fatty acids, fatty acid esters, in particular triglycerides of fatty acids, lanolin, natural and synthetic oils or waxes and emulsifiers in the presence of water.
Further preferred embodiments are oily lotions based on natural or synthetic oils and waxes, lanolin, fatty acid esters, in particular triglycerides of fatty acids, or oily-alcoholic lotions based on a lower alcohol, such as ethanol, or a glycerol, such as propylene glycol, and/or a polyol, such as glycerol, and oils, waxes and fatty acid esters, such as triglycerides of fatty acids.
The composition according to the invention may also be in the form of an alcoholic gel which comprises one or more lower alcohols or polyols, such as ethanol, propylene glycol or glycerol, and a thickener, such as siliceous earth. The oily-alcoholic gels also comprise natural or synthetic oil or wax. The solid sticks consist of natural or synthetic waxes and oils, fatty alcohols, fatty acids, fatty acid esters, lanolin and other fatty substances. If a composition is formulated as an aerosol, the customary propellants, such as alkanes, fluoroalkanes and chlorofluoroalkanes, are generally used.
The cosmetic composition may also be used to protect the hair against photochemical damage in order to prevent changes of colour shade, bleaching or damage of a mechanical nature. In this case, a suitable formulation is in the form of a rinse-out shampoo, lotion, gel or emulsion, the composition in question being applied before or after shampooing, before or after colouring or bleaching or before or after permanent waving. It is also possible to select a composition in the form of a lotion or gel for styling or treating the hair, in the form of a lotion or gel for brushing or blow-waving, in the form of a hair lacquer, permanent waving composition, colorant or bleach for the hair. Besides one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA the composition having light-protection properties may comprise various adjuvants used in this type of composition, such as surfactants, thickeners, polymers, softeners, preservatives, foam stabilisers, electrolytes, organic solvents, silicone derivatives, oils, waxes, antigrease agents, dyes and/or pigments which colour the composition itself or the hair, or other ingredients usually used for hair care.
The present invention furthermore relates to a process for the preparation of a composition which is characterised in that one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA are mixed with a cosmetically or dermatologically carrier, and to the use of one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA for the preparation of a
composition.
The compositions according to the invention can be prepared here with the aid of techniques which are well known to the person skilled in the art.
The mixing can result in dissolution, emulsification or dispersal of FAA derivatives. The positive effects of one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA give rise to their particular suitability for use in cosmetic or pharmaceutical compositions. Due to their action, one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA are preferable also suitable as medicament ingredients. One or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA can be used, for example, for preventative treatment of inflammation and allergies of the skin and in certain cases for preventing certain types of cancer. One or more of the compounds according to formula (I)1 preferably
FAA and/or its derivatives, and especially FAA are particularly suitable for the preparation of a medicament for the treatment of inflammation, allergies and irritation, in particular of the skin. It is furthermore possible to prepare medicaments which act as a vein tonic, as cuperose inhibitor, as chemical, physical or actinic erythema inhibitor, as agent for the treatment of sensitive skin, as decongestant, as desiccant, as slimming agent, as anti-wrinkle agent, as stimulator for the synthesis of components of the extracellular matrix, as strengthening agent for improving skin elasticity, and as anti- ageing agent. Furthermore, one or more of the compounds according to formula (I), preferably FAA and/or its derivatives, and especially FAA exhibit antiallergic and antiinflammatory and antiirritative actions. They are therefore suitable for the preparation of medicaments for the treatment of inflammation or allergic reactions.
The invention is explained in greater detail below by means of examples. The invention can be carried out throughout the range claimed and is not restricted to the examples given here.
Moreover, the following examples are given in order to assist the skilled artisan to better understand the present invention by way of exemplification. The examples are not intended to limit the scope of protection conferred by the claims. The features, properties and advantages exemplified for the compounds, compositions and/or uses defined in the examples may be assigned to other compounds, compositions and/or uses not specifically described and/or defined in the examples, but falling under the scope of what is defined in the claims.
Example 1 : DNA-Microarray Studies
Skin has been among the first organs analysed using DNA microarrays.
Epidermal keratinocytes have been the target of many studies because they respond to a rich variety of inflammatory and immunmodulating cytokines, hormones, vitamins, ultraviolet (UV) light, toxins and physical injury. In the present study, altered gene expression after applying FAA to a human skin model is analysed with Affymetrix oligonucleotide microarrays.
For gene expression studies human skin equivalents were treated with FAA with a concentration of 50μM in PBS-buffer/DMSO. Buffer-treated skin equivalents served as controls. Pooled samples from three biological replicates per conditions were used for microarray hybridizations.
Genes with a fold-change above 1.5 in the comparison of treated and control samples were considered as de-regulated by FAA. 219 up-regulated and 185 down-regulated genes were identified. Positive Iog2-ratio values indicate an upregulation and negative Iog2-ratio values a downregulation of the relevant gene.
Table 1: Genes deregulated by treatment of skin with FAA
GeneOntplogy biological process categories were scored for an enrichment of de-regulated genes using a hypergeometric test. Whereas no significantly enriched categories were found for the up-regulated genes, the categories shown in Table 2 exhibit a significant overrepresentation of down-regulated genes.
Table 2: Gene Ontology biological processes with an enrichment of genes that are down-regulated by FAA.
The cDNA microarray analysis of treated skin with FAA reveals many deregulated genes related to cell organization and communication, also mediated by integrins and GPCRs. The most relevant pathway map (the top scored maps resulted using Metacore software (GeneGo Inc., San Diego, USA)) is extracellular matrix (ECM) remodeling. Extracellular matrix (ECM) remodeling comprises the processes like collagen catabolic process, tissue remodeling and wound healing. The adhesion of cells to the extracellular matrix (ECM) is a dynamic process, mediated by a series of matrix-associated and cell-surface molecules that interact with each other in a spatially and temporally regulated manner.
These interactions play a major role in tissue formation, cellular migration and the induction of adhesion-mediated transmembrane signals.
The extracellular matrix (ECM) is the extracellular part of tissue that usually provides structural support to the cells in addition to performing various important functions. Formation of the ECM is essential for processes like growth, wound healing, and fibrosis. The extracellular matrix is the defining feature of connective tissue. The ECM and cell adhesion and migration processes in fact plays at least three important roles relevant in cosmetics: i) Mechanical: tensile and compressive strength and elasticity, ii) Protection: buffering against extracellular change and retention of water, iii)
Organization: control of cell behavior by binding of growth factors and interaction will cell-surface receptors.
The ECM's main components are various glycoproteins like collagens, fibrin, elastin, fibronectins, laminins, and nidogens and other molecular compounds like proteoglycans and hyaluronic acid.
The effects of FAA on the gene level give us new insights into the potential action of the compound FAA in a variety of skin/hair regeneration processes and disorders. Interactions with integrins and thus promotion of extracellular matrix proteins and a consecutive increased of matrix organization capacity, may cause anti-wrinkle effects, anti-inflammation effects and promotion of hair growth in hair cycles and regarding to the hair follicle development.
Thus, the outcome of cDNA data analysis that is listed in Table 2
(downregulated and up-regulated genes) and/or the further advantageous properties discussed herein preferably sustain an advantageous application of FAA in several categories in cosmetics like anti-aging (regarding intrinsic or extrinsic aging), anti-inflammation (photodamage, collagen catabolic process), anti psoriasis (up-regulated in psoriatic lesional skin, down- regulated by FAA) and hair care. Some examples: description of some of the deregulated genes obtained after the treatment of skin with FAA
S100 calcium binding protein A7 and S100 calcium binding protein A12 are downregulated genes after treatment of skin cells with FAA.
S100A7A may be involved in epidermal differentiation and inflammation and might therefore be important for the pathogenesis of psoriasis and other diseases. The S100A7 protein, also known as psoriasin, has important functions as a mediator and regulator in skin differentiation and disease (psoriasis), in breast cancer, and as a chemotactic factor for inflammatory cells (Kulski et al., Journal of Molecular Evolution (2003), 56(4), 397-406). In addition, Lener et al. investigate genes involved in the natural aging process of the human skin. They found that in total 105 genes change their expression over 1.7-fold during the aging process in the human skin.
S100A7 has been described as a gene that is up-regulated in old skin (T. Lener et al., Experimental Gerontology 41 (2006), 387-397).
S100 proteins are the largest subgroup of Ca2+ binding proteins with the EF- hand structural motif. A unique feature of this protein family is that individual members are localized in specific cellular compartments. For example, various S 100 proteins are expressed in very restricted regions of the hair follicle (Kizawa K et al., Methods MoI Biol. (2005).
Extracellular proteases are crucial regulators of cell function. The family of matrix metalloproteinases (MMPs) has classically been described in the context of extracellular matrix (ECM) remodeling, which occurs throughout life in diverse processes that range from tissue morphogenesis to wound healing. Recent evidence has implicated MMPs in the regulation of other functions, including survival, angiogenesis, inflammation and signaling.
Skin aging is influenced by several factors, including genetics, environmental exposure (ultraviolet (UV) irradiation, , xenobiotics, mechanical stress ), hormonal changes, and metabolic processes. The typical appearance of photoaged and chronologically aged human skin can be readily
distinguished, recent evidence indicates that chronologically aged and UV- irradiated skin share important molecular features including altered signal transduction pathways that promote matrix-metalloproteinase (MMP) expression, decreased procollagen synthesis, and connective tissue damage. Chronologically aged skin appears thin, smooth, dry, unblemished, with some loss of elasticity.
The UV-induced signal cascades enter the nucleus. MAP kinase activation results in induction of transcription factor AP-1 that is a major effector of the MAP kinase pathways. AP-1 regulates expression of many genes involved in the regulation of cellular growth and differentiation. Transcription of several MMP (matrix-metalloproteinase) family members is strongly regulated by AP- 1. Several MMPs are upregulated by AP-1. These include MMP-1 (interstitial collagenase or collagenase 1) which initiates degradation of types I and III fibrillar collagens, MMP-9 (gelatinase B), which further degrades collagen fragments generated by collagenases, and MMP-3 (stromelysin 1), which degrades type IV collagen of the basement membrane and activates proMMP-1. MMP induction is, in part, responsible for UV-induced damage to skin connective tissue. Together, MMP-1 , MMP-3, and MMP-9 have the capacity to completely degrade mature fibrillar collagen in skin. Consistent with this, increased collagen breakdown has been demonstrated within 24 h after UV irradiation in human skin in vivo. Thus, UV irradiation of human skin causes extracellular matrix degradation via induction of transcription factor AP-1 , and subsequent increased MMP production.
Down-regulation of type I collagen is mediated in part by UV-induced AP-1 , which negatively regulates transcription of both genes that encode for type I procollagen (COL1A1 and COL1A2). (Source: Laure Rittie, Gary J. Fisher; UV-light-induced signal cascades and skin aging; Ageing Research Reviews 1 (2002) 705-720.)
MMPs are secreted from keratinocytes and fibroblasts and break down collagen and other proteins that comprise the dermal extracellular matrix. Imperfect repair of the dermal damage impairs the functional and structural integrity of the extracellular matrix. Repeated sun exposure causes accumulation of dermal damage that eventually results in characteristic wrinkling of photodamaged skin (Gary J. Fisher et al., ARCH DERMATOL, vol. 138 (2002). In the skin, the primary role of MMP enzymes is to recycle skin matrix, particularly the structural proteins collagen and elastin. Reduces MMP activities degrade skin connective tissue and prevents loss of procollagen expression.
Decreasing the expression or activity of matrix metalloproteases has an effect on the biological collagen catabolic process towards skin treatment of aging and psoriasis.
The downregulated MMP genes after treatment of skin cells with FAA are MMP3, 9, 10. It is likely that downregulation of MMPs results in increase of collagen fibrils. Also, collagen-alpha type I (COL1A1), collagen-type Vl
(COL6A1), Fibroblast growth factor 2 (FGF2), fibronectin 1 (FN 1) and insulin- like growth factor binding protein 3 (IGFBP3) and hyaluronan synthase 2 (HAS2) have been upregulated.
MMP9 is strongly down-regulated after treatment of skin cells with FAA. This motivates the hypothesis that FAA activates upregulation of dermal fibroblast collagen production and downregulation of collagen degradation.
Ultraviolet (UV) irradiation from the sun reduces production of type I procollagen (COLI), the major structural protein in human skin. Photo-aging is the most common form of skin damage and is associated with skin carcinoma. After UV irradiation following genes are over-expressed in human epidermal keratinocytes, which are significantly downregulated in treated skin with FAA: Aquaporin 3, TNFSF9 (tumor necrosis factor (ligand) superfamily, member 9), MMP10, Keratin 1, Loricrin [A. Pisarchik et al. / Gene 341 (2004) 199-207]
It is known that the inhibition of BMP signaling affects growth and
differentiation in the anagen hair follicle. BMP stimulate differentiation of epidermal and hair follicle keratinocytes, inhibit initiation of hair growth, promote melanocyte proliferation and modulate melanogenesis, as well as an increase in calcitonin gene-related peptide expression in sensory neurons innervating skin. Downregulation of BMP-2 retards the entry in catagen phase in hair follicle cycling. Inhibition of BMP signaling also results in the generation of new intestinal stem cell proliferation (noggin is the natural inhibitor of BMP signaling - L.M. Hogan et al., The EMBO Journal (2000)). BMP-2 suppresses proliferative activity and support diffentiation, while FGF2 (fibroblast growth factor-2) and Follistatin stimulates hair follicle development in vitro and induces anagen phase of hair follicle growth (Paus R., Physiol
Rev (2001), 81:449-494; NAKAMURA et al, The FASEB Journal Vol. 17 March 2003).
In the treated skin with FAA, BMP-2 is downregulated, while FGF2 and transmembrane protein with EGF-like domain and two follistatin-like domains 2 (TMEFF2) are significantly upregulated.
Sphingosine-1 -phosphate (S1 P) is the ligand for a family of specific G protein coupled receptors (GPCRs) that regulate a wide variety of cellular functions, including cytoskeletal rearrangements and cell motility. Due to the pivotal role of S1 P, its levels are low and tightly regulated in a spatial-temporal manner through its synthesis catalyzed by sphingosine kinases (SphK) and degradation by an S1P lyase and specific S1P phosphatases (SPP). In the treated skin with FAA, sphingosine-1 -phosphate phosphatase 2 (SGPP2) expression is downregulated. It is known that the downregulation of SPP-1 enhanced migration towards EGF [Herve Le Stunff et al., J. Biol. Chem, 10., 2004].
EGF (Epidermal Growth Factor) is a naturally occurring protein found in skin and is a molecule that increases skin cell renewal. In the treated skin with FAA the EGF-like-domain (EGFL8) expression is higly upregulated.
EGF has been shown to be a key player in the cell growth and differentiation process.
Dermatopontin (DPT) is a widely distributed small molecular weight protein in the extracellular matrix (ECM). Dermatopontin (DPT)-null mice, generated by targeted disruption of Dpt gene, display abnormal collagen fibril formation and increased elasticity in skin. We have also shown the lack of DPT may cause decreased collagen deposition in skin. Skin wound healing is a series of complex matrix-cell interactions that involve cellular migration and inflammation, followed by proliferation of fibroblasts with new collagen synthesis, and lastly tissue remodeling of the scar. These findings suggest that DPT may function in remodeling wound matrix in a process that involves fibrillar collagen organization (Takada Ushio et at., Connective tissue
34(1 ),78, 2002). In treated skin with FAA , DPT expression is highly upregulated.
The keratinization process is affected by FAA , which motivates its use for the treatment of psoriasis.
Following the approach of Lamb et al. (Science 313 (2006), 1929-35), the genome-wide expression signature of human skin treatment with FAA is compared to a database of 1667 genome-wide expression signatures from the public domain and in-house microarray experiments. As described in detail by Lamb et al., a computational method is used that quantifies the similarity between any two given expression signatures by a Kolmogorow- Smirnov statistic. When the expression signature of human skin treatment with FAA is compared to all database signatures, the second most similar among all 1667 database signatures is from a study comparing non-lesional and lesional skin from psoriasis vulgaris patients (Reischl et al., J Invest Dermatol. 127 (2007), 163-9). This means that many genes with higher expression in lesional vs non-lesional skin of psoriasis patients are down- regulated by FAA , and vice versa, suggesting a strong link between the treatment effects of FAA and the psoriasis phenotype.
Example 2: Formulations
Formulations for compositions, preferably non-therapeutic compositions, cosmetic compositions and/or topical compositions, comprising the
Compound are shown by way of example below. For some commercially available compounds the INCI names are given.
UV-Pearls™ OMC stands for the composition with the INCI: water (for EU: Aqua), Ethylhexyl Methoxycinnamate, Silica, PVP, Chlorphenesin, BHT; this composition is commercially available under the name EusolexΘUV Pearl™ OMC from Merck KGaA, Darmstadt. The other UV Pearl products indicated in the tables are each of analogous composition with OMC replaced by the UV filter indicated.
Table 3a: W/O-Emulsion (weight-%)
Table 3b: (amounts in % w/w)
Table 4a: O/W-Emulsion, (weight-%)
Table 4b (amounts in % w/w)
Table 5: Gel, (weight-%)
Table 6a: O/W emulsions (amounts in % w/w ) Table 6b (amounts in % w/w)
Table 7: W/O emulsions, (amounts in % w/w )
Table 8: ointment (water-free) amounts in % w/w
Table 9: Oil-Gel (water-free), amounts in % w/w
Table 10: Emulsion with 0.5 % FAA
Ref. 86/08/NF2
pH = 4.36
Viscosita (25°C) Helipath T-C 2.5 rpm = 220,000 mPa.s
5 rpm = 110,000 mPa.s
Organoleptically stable after 3 months at 42.5 0C, 4°C and room temperature.
Table 11 : Emulsion with 0.1 % FAA
Ref. 86/08/NF2/01
pH = 4.15
Viscosita (25°C) Helipath T-C 2.5 rpm = 200,000 mPa.s
5 rpm = 100,000 mPa.s
Organoleptically stable after 3 months at 42.5 0C, 4°C and room temperature.
Table 12a: Lotion with 0.5% FAA
Ref. 86/08/L
pH = 3.98
° Viscosity (25°C) < 20 mPa.s
Organoleptically stable after 3 months at 42.5 0C1 4°C and room temperature.
5 Table 12b: Lotion with 0.1 % FAA
Ref. 86/08/L2
0 pH = 4.10
Viscosity (250C) < 20 mPa.s
5
Organoleptically stable after 3 months at 42.5 0C1 40C and room temperature.
0

Claims

Claims
1) Composition for topical use comprising one or more compounds of formula (I),
wherein
Z is O, S or NH;
R1, R2 and R3 are independently of each other selected from
OH1 OA, NO2, NH2, NHA, NA2, NHCOA, CONH2, CONHA and CONA2, wherein A is independently selected from Ci- to C6-alkyl groups;
halogen and thfluoromethyl;
methyl, ethyl and straight-chain or branched C3- to C2o-alkyl groups; ethenyl and straight-chain or branched C3- to C2o-alkenyl groups;
methoxy, ethoxy and straight-chain or branched C3- to C∑o-alkoxy groups;
formyl, acetyl and straight-chain or branched C3- to C20-acyl groups; hydroxymethyl, hydroxyethyl and straight-chain or branched C3- to C2o-hydroxyalkyl groups, where the hydroxyl group may be bonded to a primary or secondary carbon atom of the chain and furthermore the alkyl chain may also be interrupted by oxygen;
Cr to C2o-carboxyl groups;
-0-(CH2)I-COOH, where I = 1 to 20; C3- to C-io-cycloalkyl groups and/or C3- to C-i2-cycloalkenyl groups, where the rings may each also be bridged by -(CHb)nV- groups, where m = 1 to 3, and
phenyl, halogenophenyl, phenoxy and benzoyl groups;
where n = 0 to 6, o = 0 to 3, and p = 0 to 5,
and/or a salt or solvate thereof.and one or more topically acceptable vehicles.
2) Composition according to claim 1 , wherein said one or more compounds of formula (I) are selected from compounds of formula (II)
wherein
R1 is selected from
- OH, OCH3, NO2, NH2, NHCOCH3, COOH, CONH2, COCH3, F, Cl, CF3;
- methyl, ethyl, straight-chain or branched C3- to Ci2-alkyl groups;
- phenyl, fluorophenyl and/or phenoxy groups;
and o is O, 1 , 2 or 3;
R2 is selected from
- OH, OCH3, NO2, NH2, NHCOCH3, COOH, CONH2, COCH3, F, Cl, CF3;
- methyl, ethyl, straight-chain or branched C3- to C-ι2-alkyl groups;
- phenyl, fluorophenyl and/or phenoxy groups;
R3 is selected from
- OH, OCH3, NO2, NH2, NHCOCH3, COOH, CONH2, COCH3, F, Cl, CF3; - methyl, ethyl, straight-chain or branched C3- to Ci2-alkyl groups;
- phenyl, fluorophenyl and/or phenoxy groups;
and p is 0,1 , 2, 3, 4 or 5,
and/or a salt or solvate thereof, and one or more topically acceptable vehicles.
3) Composition according to claims 1 or 2, wherein said one or more compounds according to formula (I) are selected from the group consisting of:
4-OXO-4H-[1 ]-BENZOPYRAN-8-
ACETIC ACID [flavone-8-acetic
acid/FAA]
6-METHYL-2-PHENYL-4-OXO-4H- 6-METHOXY-2-PHENYL-4-OXO-4H- [1]-BENZOPYRAN-8-ACETIC ACID [1]-BENZOPYRAN-8-ACETΪC ACID
6-HYDROXY-2-PHENYL-4-OXO- 2-(4-METHOXYPHENYL)-4-OXO-4H-
4H-[1 ]-BENZOPYRAN-8-ACETIC [1]-BENZOPYRAN-8-ACETIC ACID
ACID
-(3,4-DIPHENYLPHENYL)-4-OXO- 3-METHOXY-4-OXO-2-PHENYL-4H-
4H-[1 ]-BENZOPYRAN-8-ACETIC [1J-BENZOPYRAN-8-ACETIC ACID
ACID
5-METHOXY-4-OXO-2-PHENYL- 2-(2-METHOXYPHENYL)-4-OXO-4H-
4H-[1 l-BENZOPYRAN-β-ACETIC [1]-BENZOPYRAN-8-ACETIC ACID
ACID
3-HYDROXY-4-OXO-2-PH ENYL- HYDROXY-5-OXO-4-PHENYL-2-4H-
4H-[1 l-BENZOPYRAN-δ-ACETIC [1]-BENZOPYRAN-8-ACETIC ACID
ACID
7-HYDROXY-4-OXO-2-PHENYL- 2-(2-HYD ROXYPH EN YL)-4-OXO-4H-
4H-[1 ]-BENZOPYRAN-8-ACETIC [1]-BENZOPYRAN-8-ACETIC ACID
ACID
2-(4-HYDROXYPHENYL)-4-OXO-
4H-[1 ]-BENZOPYRAN-8-ACETIC 2-(2-PHENOXYPHENYL)-4-OXO-4H-
ACID [1]-BENZOPYRAN-8-ACETIC ACID
6-FLUORO-4-OXO-2-PHENYL-4H- 2-(2-FLUOROPHENYL)-4-OXO-4H- [1]-BENZOPYRAN-8-ACETIC ACID [1]-BENZOPYRAN-8-ACETIC ACID
2-(4-FLUOROPHENYL)-4-OXO-4H- 2-(3-FLUOROPHENYL)-4-OXO-4H- [1]-BENZOPYRAN-8-ACETIC ACID [1]-BENZOPYRAN-8-ACETIC ACID
2-(4-PHENYLPHENYL H-OXO-4H- 2-(4-CHLOROPHENYL)-4-OXO-4H- [1]-BENZOPYRAN-8-ACETIC ACID [1]-BENZOPYRAN-8-ACETIC ACID
2-(4-CARBOXYPHENYL)-4-OXO- 2-(4-(2-FLUOROPHENYL)-PHENYL)-
4H-[1 l-BENZOPYRAN-δ-ACETIC 4-OXO-4H-[1]-BENZOPYRAN-8-
ACID ACETIC ACID
2-(2-NITROPHENYL)-4-OXO-4H- 2-(3-NITROPHENYL)-4-OXO-4H-[1]- [1]-BENZOPYRAN-8-ACETIC ACID BENZOPYRAN-8-ACETIC ACID
2-(4-NITROPHENYL)-4-OXO-4H- 2-(3-AMINOPHENYL)-4-OXO-4H-[1 ]- [1]-BENZOPYRAN-8-ACETIC ACID BENZOPYRAN-8-ACETIC ACID
2-(4-AMINOPHENYL)-4-OXO-4H- 2-(2-AMINOPHENYL)-4-OXO-4H-[1]- [1]-BENZOPYRAN-8-ACETIC ACID BENZOPYRAN-8-ACETIC ACID
2-(2-CHLOROPHENYL)-4-OXO-4H- 2-(3-CHLOROPHENYL)-4-OXO-4H- [1]-BENZOPYRAN-8-ACETIC ACID [1]-BENZOPYRAN-8-ACETIC ACID
2- 4(2H --A[1C]-EBTEANMZ.ODPOYPRHAENN-Y8-LA)-C4-EOTXICO-
ACID
-(4-ACETAMIDOPHENYL)-4-OXO- 2-(3-NITRO-4-CHLOROPHENYL)-4-
4H-[1]-BENZOPYRAN-8-ACETIC OXO-4H-[1 ]-BENZOPYRAN-8-
ACID ACETIC ACID
2-(2,4-DIMETHOXYPHENYL)-4- 2-(4-CARBAMOYLPHENYL)-4-OXO-
OXO-4H-[1 ]-BENZ0PYRAN-8- 4H-[1 ]-BENZOPYRAN-8-ACETIC
ACETIC ACID ACID
2-(4-HEXYLPHENYL)-4-OXO-4H-[1 ]-
2-(3,5 DIMETHOXYPHENYL)-4- BENZOPYRAN-8-ACETIC ACID
OXO-4H-[1]-BENZOPYRAN-8-
ACETIC ACID
2-(3-METHYLPHENYL)-4-OXO-4H- 2-(4-UNDECYLPHENYL H-OXO-4H- [13-BENZOPYRAN-8-ACETIC ACID [1]-BENZOPYRAN-8-ACETIC ACID
2-(3-NITRO-4-PHENYLPHENYL)-4- 2-(4-TRIFLUOROMETHYLPHENYL)-
OXO-4H-[1 ]BENZOPYRAN-8- 4-OXO-4H-[1 ]-BENZOPYRAN-8-
ACETIC ACID ACETIC ACID
2-(3-NITRO-4-METHOXYPHENYL)- 2-(4-TERBUTYLPHENYL)-4-OXO-4H-
4-OXO-4H-[1 ]-BENZOPYRAN-8- [1J-BENZOPYRAN-8-ACETIC ACID
ACETIC ACID and/or a salt or solvate thereof, and one or more topically acceptable vehicles.
4) Composition according to claim 1 , 2 or 3, wherein the compound
according to formula (I) comprises flavone acetic acid and/or an alkali salt, in particular the sodium salt, or solvate thereof, and one or more topically acceptable vehicles.
5) Composition for topical use comprising
a) one or more compounds of formula (I) according to Claim 1 , 2, 3 or 4, b) one or more skin-tolerated and/or hair-tolerated vehicles, and
c) optionally one or more further active compounds having a skin-care, hair care and/or inflammation-inhibiting action. 6) Composition according to Claim 1 , 2, 3, 4 or 5, wherein the one or more compounds according to formula (I) are contained in said composition in an amount of 0.01 per cent by weight up to 20 per cent by weight.
7) Composition according to one ore more of the Claims 1 to 6, comprising at least one further skin-care and/or hair care ingredient other than the one or more compounds according to formula (I), and at least one carrier which is suitable for topical applications.
8) Composition according to one ore more of the Claims 5 to 7, comprising as a further skin-care ingredient ectoine, preferably in an amount of 0.01 to
10 per cent by weight, more preferably 0.1 to 5 per cent by weight and especially 0.1 to 2 per cent by weight.
9) Use of one or more compounds of formula (I) according to one or more of claims 1 , 2, 3, 4 and 5 for the manufacture of a cosmetic composition.
10) Use of one or more compounds of formula (I) according to one or more of claims 1 , 2, 3, 4 and 5 for the preparation of a composition which is suitable for the prophylaxis and/or treatment of skin diseases which are associated with defective keratinisation relating to differentiation and cell proliferation. 11 ) Use of the one or more compounds according to formula (I) according to one or more of Claims 1 , 2, 3, 4 and 5 for the preparation of a composition for the treatment of acne vulgaris, acne comedonica, polymorphic acne, acne rosaceae, nodular acne, acne conglobata, age-related acne, acne Solaris, medicament-related acne and/or acne professionalis; for the treatment of other defects of keratinisation, in particular ichthyosis, ichthyosiform states, Darier's disease, keratosis palmoplantaris, leukoplakia, leukoplakiform states, skin and mucosal (buccal) eczema (lichen); for the treatment of other skin diseases which are associated with defective keratinisation and have an inflammatory and/or immunoallergic component; for the treatment of psoriasis relating to the skin, mucous membranes and finger- and toenails, and psoriatic rheumatism; for the treatment of skin atopy, such as eczema, and respiratory atopy; and/or for the treatment of hypertrophy of the gums. 12) Use of one or more compounds of formula (I) according to one or more of claims 1 , 2, 3, 4 and 5 for the care, preservation or improvement of the general state of the skin or hair.
13) Use of one or more compounds of formula (I) according to one or more of claims 1 , 2, 3, 4 and 5 for the regulation of hair or hair growth.
14) Use of one or more compounds of formula (I) according to one or more of claims 1 , 2, 3, 4 and 5 for the prophylaxis against or reduction of skin unevenness, wrinkles, fine lines, rough skin and/or large-pored skin.
15) Use of one or more compounds of formula (I) according to one or more of claims 1 , 2, 3, 4 and 5 for the prophylaxis against time- and/or light- induced ageing processes of the human skin and/or human hair.the prophylaxis against dry skin, wrinkle formation, the treatment or prophylaxis of pigment defects, and/or for the reduction or prevention of the harmful effects of UV rays on the skin.
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