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WO2016045902A1 - Composition anti-vieillissement comprenant du resvératrol et de l'andrographolide - Google Patents

Composition anti-vieillissement comprenant du resvératrol et de l'andrographolide Download PDF

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Publication number
WO2016045902A1
WO2016045902A1 PCT/EP2015/069551 EP2015069551W WO2016045902A1 WO 2016045902 A1 WO2016045902 A1 WO 2016045902A1 EP 2015069551 W EP2015069551 W EP 2015069551W WO 2016045902 A1 WO2016045902 A1 WO 2016045902A1
Authority
WO
WIPO (PCT)
Prior art keywords
ageing composition
ageing
resveratrol
oral
oral anti
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.)
Ceased
Application number
PCT/EP2015/069551
Other languages
English (en)
Inventor
Vishi Bansal
John Casey
Vijay Ramchandra Gadgil
Linda Jane Wainwright
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.)
Unilever NV
Conopco Inc
Original Assignee
Unilever NV
Conopco Inc
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 Unilever NV, Conopco Inc filed Critical Unilever NV
Publication of WO2016045902A1 publication Critical patent/WO2016045902A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • 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
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05—Phenols
    • 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)
    • A61K36/19—Acanthaceae (Acanthus family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/0216—Solid or semisolid forms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34—Alcohols
    • A61K8/347—Phenols
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • 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
    • A61P17/18—Antioxidants, e.g. antiradicals
    • 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
    • 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
    • A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
    • A61K2800/92—Oral administration

Definitions

  • the invention relates to an oral anti-ageing composition, in particular to an oral anti-ageing composition comprising resveratrol and an aqueous or hydroalcoholic extract of the leaf and whole herb of Andrographis paniculata.
  • NFE2L2 nuclear factor erythroid-2 related factor 2
  • Nrf2 nuclear factor erythroid-2 related factor 2
  • Nrf-2 is inactive and bound in the cytoplasm by cytosolic regulatory protein Kelch-like ECH-associated protein 1 (Keapl ).
  • Kelch-like ECH-associated protein 1 Kelch-like ECH-associated protein 1
  • the protein Cullin 3 degrades Nrf2 by ubiquitination.
  • Kobayashi et al Mol. Cell. Biol., 24, 16, 7130-9 (March 2004)
  • Keapl helps Cullin 3 ubiquitinate Nrf2.
  • Nrf2 is ubiquitinated, it is transported to the proteasome where it is degraded and its components recycled such that under normal conditions, Nrf2 has a half-life of only 20 minutes.
  • Yamamoto et al Mol. Cell (Biol., 28, 8, 2758-70 (April 2008)
  • Sekhar et al Tekhar et al
  • oxidative stress or electrophilic stress disrupts critical cysteine residues in Keapl , disrupting the Keapl -Cullin 3 ubiquitination system.
  • Nrf2 When Nrf2 is not ubiquitinated, it builds up in the cytoplasm and translocates into the nucleus.
  • Nrf2 combines (forms a heterodimer) with a small Maf protein (a transcription factor) and binds to small regions of DNA known as Antioxidant Response Elements (ARE's) in the upstream promoter region of many anti-oxidative genes, and initiates their transcription.
  • ARE's Antioxidant Response Elements
  • the antioxidant genes include "phase II" enzymes such as NAD(P)H: quinone oxidoreductase 1 (NQO-1 ) and haemoxygenase-1 (HO-1 ).
  • NAD(P)H quinone oxidoreductase 1
  • HO-1 haemoxygenase-1
  • the main function of the hair follicle is to produce a hair fibre.
  • the hair follicle develops from the embryonic epidermis as an epidermal finger which differentiates into the fibre, the outer root sheath (ORS) and the inner root sheath (IRS).
  • ORS outer root sheath
  • IFS inner root sheath
  • WO 2014/095289 Unilever et al.
  • Example 4 discloses in Example 4 that sulforaphane significantly up-regulates NQO-1 and HO-1 gene expression in human hair follicles and is thus an Nrf2 agonist, and in Example 3 that sulforaphane significantly up-regulates human hair follicle growth.
  • Hair ageing is a major age-related consumer issue (hair loss, thinning hair, loss of shine, increased number of grey hairs, etc).
  • Biological routes for hair growth or preventing hair greying provide effective opportunities to target consumer hair issues.
  • Minoxidil TM and FinasterideTM are the only clinically proven, mildly effective products available for hair growth and both are classified as medicines and therefore not suitable for cosmetic use.
  • the identification of cosmetic ingredients which are able to boost hair growth, maintain anagen and/or prevent catagen may prove to be effective anti-ageing treatments to prevent or attenuate some of the symptoms associated with hair ageing.
  • the inventors have observed a synergistic up-regulation of haemoxygenase-1 (HO-1 ) in primary human dermal fibroblast cells treated with a combination of aqueous extract of the whole herb of Andrographis paniculata and resveratrol.
  • HO-1 haemoxygenase-1
  • an oral anti-ageing composition comprising resveratrol and an aqueous or hydroalcoholic extract of the leaf and whole herb of Andrographis paniculata, wherein the oral or topical anti-ageing composition comprises more than 0.4 % w/w andrographolide, wherein the oral anti-ageing composition comprises a daily dosage of 10 to 500, preferably 50 to 300 mg resveratrol in the form of one or more unit doses.
  • the oral anti-ageing composition of the first aspect of the invention is provided for use as a medicament.
  • the oral anti-ageing composition of the first aspect is provided for use in evening skin tone, or treating or preventing hyperpigmentation.
  • the oral or topical anti-ageing composition of the first aspect of the invention is provided for use in treating hair ageing.
  • treating hair ageing means promoting hair fibre growth or reducing hair fibre loss.
  • the oral anti-ageing composition of the invention comprises a daily dosage of 10 to 500, preferably 50 to 250 mg aqueous or hydroalcoholic extract of the leaf and whole herb of Andrographis paniculata in the form of one or more unit doses.
  • the aqueous or hydroalcoholic extract of the leaf and whole herb of Andrographis paniculata comprises at least 5, preferably at least 10, most preferably at least 20 % w/w andrographolide.
  • the oral anti-ageing composition comprises no more than 20, more preferably 10, most preferably 5 % w/w andrographolide.
  • the oral anti-ageing composition of the invention may be in the form of a solid, a slurry, a solution, a suspension, a gel or an emulsion.
  • the oral anti-ageing composition of the invention may be in the form of a supplement of one or more unit dosages such as capsules, cachets, lozenges, pills, tablets, caplets, each comprising a predetermined amount of the essential ingredients of the invention.
  • the oral anti-ageing composition of the invention may be selected from the group of foodstuffs consisting of a beverage (for example a fruit or tea (for example Camellia sinensis) based beverage, a supplement, a soup (in dry, paste or liquid form), margarine, a ready- to-eat meal, a dressing, a mayonnaise, mustard, a tomato-based condiment, a sauce, a seasoning (for example as unit doses in the form of a powder, a compressed powder in the form of, for example, a cube, a liquid or suspension, or a gel), a yoghurt and a frozen confection.
  • frozen confection is meant a sweet-tasting fabricated foodstuff intended for consumption in the frozen state (i.e. under conditions wherein the temperature of the foodstuff is less than 0°C, and preferably under conditions wherein the foodstuff comprises significant amounts of ice).
  • Frozen confections include ice cream, sorbet, sherbet, frozen yoghurt, water ice, milk ice and the like.
  • the frozen confection has a total solids content (i.e. the sum of the weights of all the ingredients other than water, expressed as a percentage of the total weight) of at least 20 %, more preferably at least 25 %.
  • Frozen confections may be aerated or unaerated.
  • the frozen confection is aerated.
  • the frozen confection may be manufactured by any suitable process, typically by preparing a mix of ingredients; then pasteurising and optionally homogenising the mix; and then freezing and optionally aerating the mix to produce the frozen confection.
  • DMEM Dulbecco's Modified Eagle Serum
  • FBS foetal bovine serum
  • Test solutions were prepared in ethanol or DMSO and added directly to the cells and treated for 24 hours.
  • the test solutions were prepared with selected concentrations of test material as set forth in Table 2. The cells were then pelleted.
  • the lysis buffer contained 1 % NP-40, 0.1 % sodium deoxycholate, 0.1 % SDS, 6 mM sodium chloride and 0.05 M Tris at pH 7.6.
  • Protease inhibitor cocktail 1000X; Sigma P8340 was added prior to use at a level of 10 ⁇ per ml of lysis buffer.
  • the clarified cell lysate was frozen at -80 °C until needed.
  • the total protein concentration of each cell lysate was measured using the Pierce BCA protein assay kit.
  • a set of eight standard solutions ranging from 0 to 1200 ⁇ g/ml protein was prepared from the supplied 2 mg/ml BSA stock solution. 10 ⁇ I of standard or cell lysate was added to duplicate wells of a flat-bottomed, 96-well microtitre plate.
  • the reagent solution was prepared according to the kit instructions from 50 parts reagent A and 1 part reagent B. 200 ⁇ of the final reagent was added to each well of the microtitre plate. The plate was mixed, covered and incubated at 37 °C for 30 minutes and absorbance read at 562 nm. A protein standard curve was constructed and used to determine the protein concentration of each cell lysate.
  • Protein samples were diluted in sample diluent, and 100 ⁇ transferred to the pre-coated anti- human HO-1 immunoassay plate (Assay Designs (ERK-800)).
  • a 7-point recombinant HO-1 standard curve ranging from 25 to 0.39 ng/ml, was also prepared in sample diluent.
  • the immunoassay plate was incubated at room temperature for 30 minutes, washed six times with Wash Buffer, and incubated for a further 60 minutes at room temperature with 100 ⁇ /well of anti- human HO-1 antibody solution. The plate was washed as above and incubated for 30 minutes at room temperature with 100 ⁇ /well of horseradish peroxidase conjugate solution.
  • the results are summarised in Table 1.
  • the vehicle for the aqueous extract of the whole herb of Andrographis paniculata was distilled water, and the vehicle for dimethyl sulphoxide (DMSO) and the combination was a 50/50 by volume mixture of distilled water and DMSO.
  • the results show that 5 ⁇ resveratrol did not up-regulate HO-1 protein levels in primary human dermal fibroblast cells compared to vehicle.
  • HO-1 protein pg ⁇ g protein
  • normalised HO-1 protein pg ⁇ g protein
  • levels of primary human dermal fibroblast cells treated with resveratrol, an aqueous extract of the whole herb of Andrographis paniculata, and mixtures thereof hatchched values indicate a synergy

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Birds (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Botany (AREA)
  • Dermatology (AREA)
  • Nutrition Science (AREA)
  • Physiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Emergency Medicine (AREA)
  • Organic Chemistry (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Biochemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medical Informatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Gerontology & Geriatric Medicine (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Cosmetics (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

L'invention concerne une composition orale anti-vieillissement, en particulier une composition orale anti-vieillissement comprenant du resvératrol et un extrait aqueux ou hydroalcoolique de la feuille et de l'ensemble de l'herbe d'Andrographis paniculata. Les inventeurs ont observé une régulation synergique à la hausse de l'haemoxygenase-1 (HO-1) dans des cellules humaines de fibroblastes dermiques primaires, traitées par une combinaison d'extrait aqueux de l'ensemble de l'herbe d'Andrographis paniculata et de resvératrol. Ainsi, selon un premier aspect, l'invention concerne une composition orale anti-vieillissement, la composition orale anti-vieillissement comprenant du resvératrol et un extrait aqueux ou hydroalcoolique de la feuille et de l'ensemble de l'herbe d'Andrographis paniculata, la composition orale ou topique anti-vieillissement comprenant plus de 0,4 % en poids d'andrographolide, la composition orale anti-vieillissement comprenant une dose quotidienne de 10 à 500, de préférence de 50 à 300 mg de resvératrol, sous la forme d'une ou de plusieurs doses unitaires. D'autres aspects de l'invention sont également décrits.
PCT/EP2015/069551 2014-09-22 2015-08-26 Composition anti-vieillissement comprenant du resvératrol et de l'andrographolide Ceased WO2016045902A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP14185817 2014-09-22
EP14185817.5 2014-09-22

Publications (1)

Publication Number Publication Date
WO2016045902A1 true WO2016045902A1 (fr) 2016-03-31

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021184125A1 (fr) * 2020-03-19 2021-09-23 Idunn Technologies Découverte de quinze nouveaux extraits végétaux anti-âge et identification de procédés cellulaires qu'ils affectent en tant que nouveaux mimétiques de restriction calorique
WO2022255810A1 (fr) * 2021-06-04 2022-12-08 주식회사 엘지생활건강 Composition cosmétique anti-vieillissement
US20230381135A1 (en) * 2020-10-13 2023-11-30 Tilman Sa Composition comprising at least one labdane diterpene and method for manufacturing same
EP4623892A1 (fr) * 2024-03-25 2025-10-01 CUTANEON - Skin & Hair Innovations GmbH Agent actif pour le traitement de la pigmentation des cheveux

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050048008A1 (en) * 2003-08-29 2005-03-03 Bioderm Research Antiaging Cosmetic Delivery Systems
US20090162457A1 (en) * 2005-10-26 2009-06-25 Kao Corporation Resveratrol and/or grape leaf extract as i. a. endurance improver, anti-aging agent, muscle strength improver
CA2727997A1 (fr) * 2011-01-14 2012-07-14 Himalaya Global Holdings Ltd. Formule phytosanitaire solide et son procede de peparation
WO2014095289A2 (fr) * 2012-12-20 2014-06-26 Unilever Plc Méthode de traitement du vieillissement capillaire

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050048008A1 (en) * 2003-08-29 2005-03-03 Bioderm Research Antiaging Cosmetic Delivery Systems
US20090162457A1 (en) * 2005-10-26 2009-06-25 Kao Corporation Resveratrol and/or grape leaf extract as i. a. endurance improver, anti-aging agent, muscle strength improver
CA2727997A1 (fr) * 2011-01-14 2012-07-14 Himalaya Global Holdings Ltd. Formule phytosanitaire solide et son procede de peparation
WO2014095289A2 (fr) * 2012-12-20 2014-06-26 Unilever Plc Méthode de traitement du vieillissement capillaire

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021184125A1 (fr) * 2020-03-19 2021-09-23 Idunn Technologies Découverte de quinze nouveaux extraits végétaux anti-âge et identification de procédés cellulaires qu'ils affectent en tant que nouveaux mimétiques de restriction calorique
US20230381135A1 (en) * 2020-10-13 2023-11-30 Tilman Sa Composition comprising at least one labdane diterpene and method for manufacturing same
WO2022255810A1 (fr) * 2021-06-04 2022-12-08 주식회사 엘지생활건강 Composition cosmétique anti-vieillissement
EP4623892A1 (fr) * 2024-03-25 2025-10-01 CUTANEON - Skin & Hair Innovations GmbH Agent actif pour le traitement de la pigmentation des cheveux
WO2025201826A1 (fr) * 2024-03-25 2025-10-02 Cutaneon - Skin & Hair Innovations Gmbh Agent actif utilisé dans le traitement de la pigmentation capillaire

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