WO2005030228A2 - Utilisation d'une composition contenant des extraits de vitis vinifera et de lycopersicum pour proteger la peau - Google Patents

Utilisation d'une composition contenant des extraits de vitis vinifera et de lycopersicum pour proteger la peau Download PDF

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Publication number
WO2005030228A2
WO2005030228A2 PCT/EP2003/010768 EP0310768W WO2005030228A2 WO 2005030228 A2 WO2005030228 A2 WO 2005030228A2 EP 0310768 W EP0310768 W EP 0310768W WO 2005030228 A2 WO2005030228 A2 WO 2005030228A2
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vitamin
extract
use according
composition
skin
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PCT/EP2003/010768
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WO2005030228A3 (fr
Inventor
Orlando Petrini
Inka Pfizner
Jürgen BERNHARDT
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Pharmaton S.A.
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Priority to AU2003287952A priority Critical patent/AU2003287952A1/en
Priority to PCT/EP2003/010768 priority patent/WO2005030228A2/fr
Publication of WO2005030228A2 publication Critical patent/WO2005030228A2/fr
Publication of WO2005030228A3 publication Critical patent/WO2005030228A3/fr

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    • 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
    • A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/15—Vitamins
    • 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
    • A61K31/01—Hydrocarbons
    • A61K31/015—Hydrocarbons carbocyclic
    • 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 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A61K31/355—Tocopherols, e.g. vitamin E
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/04—Sulfur, selenium or tellurium; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/31—Brassicaceae or Cruciferae (Mustard family), e.g. broccoli, cabbage or kohlrabi
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/81—Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/87—Vitaceae or Ampelidaceae (Vine or Grape family), e.g. wine grapes, muscadine or peppervine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/67—Vitamins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9728—Fungi, e.g. yeasts
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9789—Magnoliopsida [dicotyledons]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/16—Emollients or protectives, e.g. against radiation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/52—Stabilizers
    • A61K2800/522—Antioxidants; Radical scavengers

Definitions

  • the invention relates to the use of a composition containing synergistic amounts of various antioxidants and optionally a suitable carrier material for preparing a pharmaceutical composition, food supplement or cosmetic agent for protecting the skin from U V rays and/or inflammatory processes.
  • the skin is exposed to a variety of external stress factors, being the boundary layer and surface of the human body.
  • the human skin is an organ which protects the body from external influences by means of differently specialised cell types such as the keratinocytes, melanocytes, Langerhans cells, Merkel cells and sense cells incorporated therein.
  • the external physical influences include thermal and mechanical influences and the effects of radiation such as UV and IR radiation.
  • the external chemical influences include in particular the effects of toxins and allergens.
  • the external biological influences include the effects of foreign organisms and their metabolic products.
  • Other stress factors are pathological conditions and diseases such as fever, inflammation, infection and cell and tissue trauma as well as physiological processes such as cell division.
  • European Patent Application EP 0712630 relates to an oral composition for preventing sun allergies.
  • the composition is based on a carotenoid, a tocopherol, ascorbic acid and selenium.
  • the carotenoids used are carotene and lycopene.
  • EP 0712630 mentions the already known combination of antioxidants with plant oil as an adjuvant in the production of capsules for oral use. Medicinal uses and/or effects apart from the effect against sun allergy of oral administration of the composition of EP 0712630 A2 have not been disclosed.
  • the invention thus relates to a composition containing synergistic amounts of antioxidants selected from the group consisting of:
  • Fig. 1 shows the diagrammatic structure of the membrane equivalent with fibroplasts (1.1), keratinocytes (1.2) and extracellular matrix proteins (1.3).
  • Fig. 2 shows the diagrammatic structure of the collagen equivalent with collagen gel (2.1) and keratinocytes (1.2).
  • Fig. 3 shows histological sections of membrane equivalents of
  • A An unsupplemented control equivalent with a differentiated keratinocyte layer
  • Fig. 4 shows histological sections of membrane equivalents of membrane equivalents [sic] after UVA irradiation (20J/cm 2 )
  • Fig. 5 shows the immune cells 24 hours after activation, immediately before “co- cultivation” with the membrane equivalents.
  • Fig. 6 shows the unsupplemented, immunostimulated membrane equivalent A with condensed cell nucleus (6.1) and a loss of the barrier integrity (6:2) and the supplemented immunostimulated membrane equivalent B with a thickened Stratum corneum (6.3), condensed cell nucleus (6.4) and a proliferating keratinocyte layer with loss of barrier integrity (6.5).
  • Fig. 7 shows haemalum/eosin staining
  • B Collagen equivalent with a differentiated keratinocyte layer (7.5), a flattened keratinocyte layer (7.6), a polygonal keratinocyte layer (7.7) and a cylindrical keratinocyte layer (7.8).
  • Fig. 8 shows haemalum/eosin staining of a collagen equivalent with a thickened Stratum corneum (8.1).
  • Fig. 9 shows a Tunel assay before UV irradiation
  • Fig. 10 shows a Tunel assay after UV irradiation
  • composition containing synergistic amounts of antioxidants selected from the group comprising vitamin E, provitamin A, vitamin C, selenium, and extract of Lycopersicum esculentum, an extract of Vitis vinifera and optionally a suitable carrier material can be administered orally or topically to protect the skin from UV rays and/or inflammatory processes.
  • the composition is preferably administered orally.
  • Tocopherols are chroman-6-ols (3,4-dihydro-2 H-1-benzopyran-6-ols) substituted in the 2 position by a 4,8,12-trimethyltridecyl group and are effective as vitamin E.
  • the commonest and most effective natural tocopherol is ⁇ -tocopherol. It occurs in many vegetable oils, particularly seed oils from soya, wheat, maize, rice, cotton, alfalfa and nuts.
  • Tocopheryl acetate, succinate, nicotinate and poly(oxyethylene)succinate are the usual forms for administration as vitamin E.
  • Provitamin A ⁇ -carotene
  • vitamin A is a precursor of vitamin A, which is oxidatively cleaved in the animal body into 2 mol of retinal and reduced to retinol (vitamin A).
  • Provitamin A is the commonest carotenoid in the plant kingdom, predominantly in the all-trans form, e.g. in carrots and crude palm oil and as an accompaniment to chlorophyll.
  • Vitamin C L-ascorbic acid, ⁇ (R)-5-[(S)-1 ,2-dihydroxyethyl]-3,4-dihydroxy- 5 H- furan- 2- one, is found in all higher plants and animals, particularly in acerola, citrus fruits, rosehips, sea buckthorn, strawberries, blackcurrants, spinach, peppercorns, horseradish, parsley and liver.
  • D- glucose is first hydrogenated to form sorbitol and then this is bacterially oxidised to form L-sorbose.
  • This ketose is converted via its bis-O-isopropylidene derivative into that of 2-oxo-L-guIonic acid and the latter is converted into L-ascorbic acid with acids.
  • Se deficiency is also associated with rheumatism and cataract; selenite is supposed to potentiate the effect of vitamin E and also detoxify the body of mercury and cadmium .
  • the human body contains approx. 10-15 mg of selenium and becomes ill when the daily food intake contains more than 1 mg of Se/g; by contrast, a minimum content of 0.02 mg Se/g is necessary to prevent deficiency symptoms.
  • Se is stored in the human body in the liver, spleen, kidneys and heart. Extract of Lycopersicum esculentum,
  • 1 kg of tomatoes contains approx. 20 mg lycopene, rosehips and other fruits where it occurs alongside its isomers, the carotenoids and the 1 ,2-epoxide as well as the 5,6-epoxide.
  • Lycopene is also present in chanterelles (Cantharellus cibarius), butter, serum and liver. Lycopene is licensed as a colouring for cosmetics and food (E 160 d).
  • the tomatoes are extracted using known methods.
  • the resulting standardised extract contains about 5 wt.% of lycopene, which is partly dissolved in natural lipids of the tomatoes and partly in crystalline form and dispersed in these lipids.
  • Extract of Vitis vinifera, red wine extract is important because it contains resveratrol as its essential ingredient.
  • Resveratrol is 3,5,4'-trihydroxy-stilbene.
  • Resveratrol is present in fairly large amounts in the skin of blue wine grapes, in red wine and grape juice, in groundnuts and mulberries.
  • Resveratrol has also been identified as the essential ingredient of "Kojo-Kon", a popular medicine in China and Japan.
  • Resveratrol is used to treat arteriosclerosis and counteracts the tendency of the blood platelets to clump together and reduces susceptibility to thrombosis.
  • Red wine extract has a protective effect against arteriosclerosis and cancer, particularly on account of its content of resveratrol.
  • Red wine with resveratrol protects the LDL particles in the blood from oxidation significantly more than a comparable amount of vitamin E, which is also an antioxidant.
  • the extract of Vitis vinifera is preferably used as in US Patent US 6,297,218 in the form of a composition containing phospholipids and vegetable oils.
  • the grapeseeds are extracted with a solvent selected from the group comprising the alcohols, such as for example ethanol, propanol or butanol, ketones, such as for example acetone or methylethylketone, and water, or with a mixture of the above solvents at a temperature from 20°C to 100°C, particularly from 40 to 80°C.
  • a solvent selected from the group comprising the alcohols, such as for example ethanol, propanol or butanol, ketones, such as for example acetone or methylethylketone, and water, or with a mixture of the above solvents at a temperature from 20°C to 100°C, particularly from 40 to 80°C.
  • the composition consists of:
  • composition for oral administration the composition is preferably used in the form of a soft or hard gelatine capsule, tablet or film-coated tablet.
  • the following carriers are preferred: natural vegetable oils, totally or partially hydrogenated vegetable oils, lecithins, plant phosphatides and natural waxes, particularly soya oil, totally or partially hydrogenated soya oil, rapeseed oil, groundnut oil, soya lecithin, soya phosphatides, egg lecithin and beeswax.
  • composition preferably consists essentially of 15 to 45 wt% of antioxidants and 55 to 85 wt% of carrier material.
  • composition according to the invention may be used in the form of suppositories or in a transdermal form.
  • the compositions may also be used according to the invention in the form of a topical composition.
  • a topical composition is prepared by incorporating the combination of the antioxidants, optionally with excipients and/or carriers, in a suitable formulation.
  • the excipients and carriers are selected from the group of carriers, preservatives and other conventional excipients.
  • the topical composition based on the combination of antioxidants is applied externally to the skin or skin adnexa.
  • Suitable formulations include, for example: solutions, suspensions, emulsions, pastes, ointments, gels, creams, lotions, powders, soaps, cleansing preparations containing surfactants, oils and sprays.
  • any other conventional carriers, excipients and possibly other active substances may be added to the composition.
  • Preferred excipients are selected from among the preservatives, stabilisers, solubilisers, vitamins, colouring agents and odour improvers.
  • Ointments, pastes, creams and gels may contain, in addition to one or more antioxidants used according to the invention, the usual carriers such as animal and vegetable fats, waxes, paraffins, starch, gum tragacanth, cellulose derivatives, polyethylene glycols, silicons, bentonite, silicic acid, talc and zinc oxide or mixtures of these substances.
  • the usual carriers such as animal and vegetable fats, waxes, paraffins, starch, gum tragacanth, cellulose derivatives, polyethylene glycols, silicons, bentonite, silicic acid, talc and zinc oxide or mixtures of these substances.
  • Powders and sprays may contain, in addition to one or more antioxidants used according to the invention, the conventional carriers, e.g. lactose, talc, silicic acid, aluminium hydroxide, calcium silicate and polyamide powders or mixtures of these substances.
  • Sprays may additionally contain the usual propellants, e.g. chlorofluorohydrocarbons, propane/butane or dimethylether.
  • the compositions which are to be applied topically may contain organic or inorganic UV filters in addition to the antioxidants used according to the invention. Such UV filters are recommended as a supplementary protection when the composition according to the invention is administered orally.
  • Suitable organic UV filters include all the UVA and UVB filters known to the skilled man. For both UV ranges there are numerous tried and tested substances known from the specialist literature, e.g. benzylidene camphor derivatives such as
  • Suitable inorganic UV filters are those selected from among the titanium dioxides, e.g. coated titanium dioxide (e.g. Eusolex® T-2000 or Eusolex® T-Aqua), zinc oxides (e.g. Sachtote®), iron oxides or cerium oxides.
  • coated titanium dioxide e.g. Eusolex® T-2000 or Eusolex® T-Aqua
  • zinc oxides e.g. Sachtote®
  • iron oxides or cerium oxides e.g. coated titanium dioxide (e.g. Eusolex® T-2000 or Eusolex® T-Aqua)
  • iron oxides e.g. Sachtote®
  • Preferred UV filters are zinc oxide, titanium dioxide, 3-(4'-methylbenzylidene)-dl- camph.or, 1-(4-tert. butylphenyl)-3-(4-methoxyphenyl)propan-1 ,3-dione, 4-isopropyldibenzoylmethane, 2-hydroxy-4-methoxy-benzophenone, octyl methoxycinnamate, 3,3,5-trimethyl-cyclohexylsalicylate, 2-ethylhexyl 4- (dimethylamino)-benzoate, 2-ethylhexyl 2-cyano-3,3-diphenylacrylate, 2-phenylbenzimidazole-5-sulphonic acid and the potassium, sodium and triethanolamine salts thereof.
  • UV filters are zinc oxide and titanium dioxide.
  • titanium dioxide is used according to the invention it is preferable to use, in addition to the titanium dioxide, one or more other UV filters selected from 3-(4'- methylbenzylidene)-dl-camphor, 1 -(4-tert-butylphenyl)-3-(4- methoxyphenyl)propan-1 ,3-dione, 4-isopropyldibenzoylmethane, 2-hydroxy-4- methoxybenzophenone, octyl methoxycinnamate, 3,3,5- trimethylcyclohexylsalicylate, 2-ethylhexyl 4-(dimethylamino)benzoate, 2- ethylhexyl 2 ⁇ cyano-3,3-diphenylacrylate, 2-phenylbenzimidazol-5-sulphonic acid and the potassium, sodium and triethanolamine salts thereof. It is particularly preferred to use, in addition to titanium dioxide, the UV filters 2- hydroxy-4-methoxybenzophenone and/or
  • Another aspect of the invention is an article of manufacture comprising packaging material contained within which is a composition containing synergistic amounts of antioxidants selected from the group comprising:
  • the packaging material comprises a label which indicates that the composition can be used to protect the skin from UV rays, ageing under the effect of UV rays and/or from inflammatory processes.
  • composition to be used according to the invention is obtainable under the trade mark Seresis ® and has the following ingredients:
  • the NHDF cells were cultivated under standardised cell culture conditions (37°C, 5% CO 2 ). To carry out the tests the cells were seeded in the corresponding plate formats. After confluence was achieved, i.e. after a continuous cell lawn had formed, the cells were supplemented.
  • the histological photographs were taken with two different in vitro skin models. These models were a membrane and a collagen equivalent based on primary pooled fibroblasts and keratinocytes of the cell line HaCaT.
  • the HaCaT cell line represents a skin keratinocyte cell line of human origin immortalised by spontaneous transformation. The use of these cells rules out inter-individual differences such as occur with primary keratinocytes, so that the models can be constructed reproducibly.
  • Membrane equivalent ( Figure 1): This model is a co-culture in which the cell types are cultivated in separate compartments. The exchange of substances in this case is provided by means of permeable membranes with a defined pore size.
  • first of all primary pooled fibroblasts are seeded in a suitable plate format and cultivated to confluence.
  • the membranes of the Transwell-Clear inserts used made by Corning, Action, MA
  • the HaCaTs are kept submerged until confluent and then maintained as an airlift culture for up to 20 days to ensure differentiation of the epidermis.
  • a further advantage of this model is that the keratinocytes are in direct contact with the culture medium over the underside of the membrane and can thus react directly to the supplementation and stress induction.
  • Collagen Equivalent ( Figure 2): This model differs from the membrane equivalent described above by its proportion of dermis.
  • the dermis is formed from fibroblasts embedded in a collagen matrix. After a short cultivation period the keratinocytes are seeded on to the collagen/ fibroblast gel, kept submerged for about two days and then maintained as an airlift culture for 12-15 days. With this model the in vivo situation can be simulated better than with the membrane equivalent. However, with systemic application of the supplements or the stressors, these have to overcome the dermis part before reaching the keratinocytes. Conse ⁇ uently, in this model, the supplementation period is longer.
  • Table 2 Solubilisers and concentrations of the individual substances in the stock solution.
  • the supplementation of the collagen equivalents was carried out 5 days before and that of the membrane equivalents 48 hours before the stress treatment. In both cases the dilution of the stock solutions used (individual substances) was 1 :1000. The discrepancy in the supplementation period can be explained, as described above, by the accessibility of the keratinocytes. In the case of the collagen equivalent the active substances have to pass through the collagen gel to reach the keratinocytes, with the result that a longer supplementation phase is required here. Table 4 shows the supplementation and treatment plan for the individual in vitro skin models.
  • the supplemented and unsupplemented control equivalents were harvested after the end of the supplementation phase and prepared for cutting using a frozen section microtome.
  • the irradiation of the skin equivalents was carried out after the supplementation phase in the "Dosimetersystem UV-AB-MAT" irradiation equipment made by G ⁇ bel UV Electronik GmbH.
  • the irradiation dose was 20 J/cm 2 UVA.
  • UVA 320-400 nm
  • the equivalents were cultivated for a further 24 hours after treatment and then prepared for the histological sections.
  • the generation of skin-infiltrating immunocomponents which in turn set off inflammatory processes is achieved by activation of the immune cells used.
  • the immune cells were also treated with the active substances in addition to the equivalents.
  • the immune cells were supplemented for 24 hours, activated and then "co-cultivated" for 3 days with the supplemented membrane equivalent.
  • the treatment of the collagen equivalents with the immune cells does not result in any visualisable effect because of the dermis component these models were excluded from this treatment.
  • the membrane equivalents were stained with the haemalum/ eosin staining which is suitable in this case for showing up the effects of the various treatments/stress induction on this model. Basically, regarding the membrane equivalents, it is found that the membrane detaches very easily during cutting with the frozen section microtome and cutting artefacts may occur, but they are easily identified. Moreover, the Tunel assay (TdT-mediated dUTP Nick End Labelling for detecting DNA strand breakages), which visualises apoptotic cells, cannot be carried out with the membrane equivalents as in this model nonspecific binding generates a high background which cannot be distinguished from the specific antigen-antibody binding.
  • TdT-mediated dUTP Nick End Labelling for detecting DNA strand breakages which visualises apoptotic cells
  • Fig. 5A very impressively shows increased “cluster” formation of the immune cells 24 hours after activation.
  • a formation of the immune cells of this kind is an indication of successful stimulation of this type of cell, which can easily be checked under the microscope.
  • the supplemented immune cells display very different characteristics in relation to the above mentioned cluster formation (Fig. 5B). There are a large number of individual cells and reduced aggregation of the cells, which strongly indicates an immunosuppressant and anti inflammatory potential of the bioactive ingredients used.
  • FIG. 6 shows the unsupplemented, immunostimulated (A) and supplemented, immunostimulated membrane equivalent (B).
  • A unsupplemented, immunostimulated
  • B supplemented, immunostimulated membrane equivalent
  • the collagen equivalents were subdivided into the following treatment groups (see Table 6) and after cutting investigated by histological (haemalum/eosin staining) and immunohistological methods (Tunel assay).
  • Fig. 7 shows, as a comparison, a cross section through normal skin. It is divided into the Stratum basale, Stratum spinosum, Stratum granulosum and Stratum corneum.
  • the keratinocytes range from cubic to highly cylindrical in shape.
  • the Stratum spinosum consists of 2-5 layers of polygonal, slightly flattened cells, whereas the keratinocytes of the Stratum granulosum have a flattened shape.
  • the corneum there are several layers of highly flattened, terminally differentiated keratinocytes, the corneocytes.
  • the structure of the collagen equivalent and the shape of the keratinocytes in the individual layers can readily be compared with the structure of the normal skin (Fig. 7B). It will immediately be realised that the cells of the Stratum basale to the Stratum corneum vary from a cylindrical shape to a flattened shape. By contrast, this model differs from normal skin in reduced differentiation of the keratinocytes to form the Stratum corneum and less creasing of the epidemis as a whole.
  • Fig. 9 shows the photographs of the control equivalents. In both cases (unsupplemented and supplemented) only individual apoptotic cells can be detected using this immuno- hystological method.
  • the biologically active ingredients (standardised tomato extract, ⁇ -Carotene suspension, ⁇ -Tocopheryl acetate, standardized grape seed extract, ascorbic acid, selenium yeast) of Seresis® were first investigated in the above-mentioned amounts for possible cytotoxic effects and for their effect on the antioxidant capacity of human skin fibroblasts (NHDF). Apart from the pure mixture of active ingredients the entire contents of an active substance capsule were also used. In addition, a number of additives (oils, etc.) were also included in the test. Using two different in vitro skin models investigations were also carried out to see to what extent the protective effects of the active substances can be visualised. For this, the models were exposed to two different stressors (UV irradiation, activated immune cells).
  • the highest concentrations of the individual active substances in the tests carried out are above the average plasma values for the lipophilic substances ( ⁇ - Tocopherol, lycopene, ⁇ -Carotene) but in a range which can be achieved by oral supplementation.
  • the highest concentration is in a non-physiological range, and this is to be regarded as less critical in hydrophilic substances (Table 2).
  • UVA irradiation was used as the stressor.
  • UVA light (320-400 nm) acts primarily by generating reactive oxygen species.
  • Reactive oxygen species are capable of oxidatively changing various substances found in the body.
  • nucleic acids, carbohydrates and proteins also present areas of attack for free radicals which may subsequently lead to cell function disorders and cell death.
  • haemalum/eosin staining was used to show up the morphological changes in the cells.
  • apoptotic cells were shown up using the TUNEL assay.
  • Activated immune cells which as a consequence of activation release inflammation mediators (lymphokines) which in turn initiate inflammatory processes, were used as a further stressor for the membrane equivalents.
  • the immune cells were also treated with the active substances in the supplemented model.
  • an altered reaction was observed in the cells treated with the active substance mixture.
  • the typical picture of "cluster" formation (an indication of successful activation) could only be observed fully in the untreated immune cells.
  • the supplemented cells there was a significantly reduced cluster formation and a large number of individual cells, strongly indicating an immuno-suppressant and anti-inflammatory potential. The extent to which this effect is subject to time limits and the precise mechanisms on which the effect is based (altered lymphokine pattern, increased cell growth, etc.) could not be explained at this stage.

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Abstract

La présente invention concerne l'utilisation d'une composition contenant des quantités synergiques d'antioxydants choisis dans le groupe formé par la vitamine E, le béta-carotène, la vitamine C, le sélénium, un extrait de Lycopersicum esculentum, un extrait de Vitis vinifera et éventuellement une matière de support adaptée, afin de préparer une composition pharmaceutique, un complément alimentaire ou un produit cosmétique conçus pour protéger la peau de rayonnements ultraviolets, du vieillissement sous l'effet de rayonnements ultraviolets et/ou de processus inflammatoires.
PCT/EP2003/010768 2003-09-27 2003-09-27 Utilisation d'une composition contenant des extraits de vitis vinifera et de lycopersicum pour proteger la peau WO2005030228A2 (fr)

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AU2003287952A AU2003287952A1 (en) 2003-09-27 2003-09-27 Use of a composition containing extracts of vitis vinifera and lycopersicum for protecting the skin
PCT/EP2003/010768 WO2005030228A2 (fr) 2003-09-27 2003-09-27 Utilisation d'une composition contenant des extraits de vitis vinifera et de lycopersicum pour proteger la peau

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010056675A2 (fr) * 2008-11-12 2010-05-20 June Jacobs Laboratories, Llc Compositions antioxydantes pour la purification et le conditionnement de la peau
CN103565694A (zh) * 2013-10-15 2014-02-12 倪生标 一种防紫外线乳液
CN108159200A (zh) * 2018-01-31 2018-06-15 湖南传世中医研究院有限公司 一种治疗颈椎病的中药制剂及其制备方法
CN114144205A (zh) * 2019-07-24 2022-03-04 赫斯特细胞有限公司 用于伤口愈合的新抗氧化剂组合物

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WO2001089542A2 (fr) * 2000-05-25 2001-11-29 Pharmaton S.A. Methode destinee a ameliorer la protection cellulaire

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WO2001089542A2 (fr) * 2000-05-25 2001-11-29 Pharmaton S.A. Methode destinee a ameliorer la protection cellulaire

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F'GUYER SLEEM ET AL: "Photochemoprevention of skin cancer by botanical agents." PHOTODERMATOLOGY PHOTOIMMUNOLOGY AND PHOTOMEDICINE, vol. 19, no. 2, April 2003 (2003-04), pages 56-72, XP009031848 ISSN: 0905-4383 *
FUCHS JUERGEN ET AL: "Modulation of uv-light-induced skin inflammation by D-alpha-tocopherol and L-ascorbic acid: A clinical study using solar simulated radiation" FREE RADICAL BIOLOGY AND MEDICINE, vol. 25, no. 9, December 1998 (1998-12), pages 1006-1012, XP002283436 ISSN: 0891-5849 *
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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010056675A2 (fr) * 2008-11-12 2010-05-20 June Jacobs Laboratories, Llc Compositions antioxydantes pour la purification et le conditionnement de la peau
WO2010056675A3 (fr) * 2008-11-12 2010-07-22 June Jacobs Laboratories, Llc Compositions antioxydantes pour la purification et le conditionnement de la peau
CN103565694A (zh) * 2013-10-15 2014-02-12 倪生标 一种防紫外线乳液
CN108159200A (zh) * 2018-01-31 2018-06-15 湖南传世中医研究院有限公司 一种治疗颈椎病的中药制剂及其制备方法
CN114144205A (zh) * 2019-07-24 2022-03-04 赫斯特细胞有限公司 用于伤口愈合的新抗氧化剂组合物

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