EP2629744A1 - Produkt zur behandlung von cellulite, hautalterung und zur prävention von entzündungsprozessen - Google Patents

Produkt zur behandlung von cellulite, hautalterung und zur prävention von entzündungsprozessen

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Publication number
EP2629744A1
EP2629744A1 EP11785733.4A EP11785733A EP2629744A1 EP 2629744 A1 EP2629744 A1 EP 2629744A1 EP 11785733 A EP11785733 A EP 11785733A EP 2629744 A1 EP2629744 A1 EP 2629744A1
Authority
EP
European Patent Office
Prior art keywords
extract
composition
oolmg
activator
compositions
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Withdrawn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
EP11785733.4A
Other languages
English (en)
French (fr)
Inventor
Brigitte Gourlaouen
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.)
Individual
Original Assignee
Individual
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 Individual filed Critical Individual
Publication of EP2629744A1 publication Critical patent/EP2629744A1/de
Withdrawn legal-status Critical Current

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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A61K8/23—Sulfur; Selenium; Tellurium; Compounds thereof
    • A—HUMAN NECESSITIES
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    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/906—Zingiberaceae (Ginger family)
    • A61K36/9066—Curcuma, e.g. common turmeric, East Indian arrowroot or mango ginger
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    • A23K20/105—Aliphatic or alicyclic compounds
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    • 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 
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Definitions

  • the invention relates to a product for cosmetic, pharmaceutical, food or veterinary use intended for the loss of the fat volume contained in the tissues and / or intended for the reduction of inflammatory processes.
  • This product comprises at least two compositions, one being administered daily, preferably in the morning, and the other at night, preferably in the evening.
  • This product makes it possible to improve cellular functioning thanks to a dual mode of action: the adaptive resynchronization of the cell, and the mechanisms of direct or indirect lipolysis.
  • the invention also relates to a cosmetic care method or a method of therapeutic treatment using these compositions.
  • the product combines two compositions: sirtuin inhibitors and heat shock proteins (HSPs) inhibitors are administered during the day, while sirtuin activators and HSP activators are provided during the night.
  • the cutaneous application or the oral intake of the compositions is carried out according to a chrono-modulated scale over twenty-four hours, according to the individual chronobiological rhythm of the man or the animal, to ensure the optimal effect of the active principles.
  • compositions useful in the field of thinning and increasing cell life are known and used daily. However, it is still unusual to use
  • compositions whose biological effects are complementary are complementary.
  • sirtuin modulators described to date in the prior art do not take into account a certain number of factors, including in particular: the memorization of repeated stress, the potential differentiation into adipocyte of certain cells (fibroblast, mesenchyme, monocytes), and the inflammatory component of the cell tissue (peroxisome proliferator activated) which in the long term can cause the occurrence of inflammatory diseases (atherosclerosis, diabetes II) to decrease the effectiveness of the desired activity.
  • it is necessary to moderate the negative effects of sirtuin-induced hyperactivity which results in over-stimulation of apoptotic P53 genes and the acceleration of metabolic senescence.
  • compositions comprising slimming agents and / or agents making it possible to prevent inflammatory phenomena, in order to preserve cell integrity in particular by having combined and alternate actions on the activity of the cells, and in particular the adipocytes.
  • compositions include sirtuin modulators.
  • the object of the invention is to solve the new technical problem consisting in improving the slimming activity of compositions containing sirtuin inhibitors.
  • the invention also aims to provide a cosmetic, pharmaceutical, food or veterinary composition, having preventive properties of inflammatory processes, in particular a repairing or protective effect of the integrity of the cell.
  • the object of the invention is to conserve and improve the beneficial activity of sirtuin modulators by seeking to minimize their deleterious effects.
  • the object of the invention is to seek to control the activity and / or to reduce the negative effects of a composition comprising activators of sirtuins.
  • the object of the invention is to seek to control the activity and / or to reduce the negative effects of a composition comprising sirtuin inhibitors.
  • the object of the invention is to solve this technical problem in a simple, inexpensive and industrially reproducible way, taking advantage advantageously of the Community Directive 76/768 / EEC relating to cosmetic products.
  • the inventor has unexpectedly found that the beneficial effects of sirtuins, such as the slimming effect and / or prevention of inflammatory processes, can be improved in accordance with the biological rhythm of the cell, by associating them with a heat modulator.
  • Shock Protein Shock Protein
  • At least one inhibitor of HSPs and at least one sirtuin inhibitor is combined with at least one activator of HSPs and at least one activator of sirtuin, in particular while respecting the alternation of the nycthemeral cycle.
  • the method of the present invention relates to a kit of slimming compositions and / or prevention of inflammatory processes, in particular cosmetic, pharmaceutical, food or veterinary processes comprising:
  • sirtuin inhibitor at least one inhibitor of at least one type of sirtuin
  • HSP inhibitor at least one inhibitor of at least one type of HSP
  • a nocturnal composition comprising at least one activator of at least one type of sirtuin (called “sirtuin activator”) and at least one activator of at least one type of HSP (called “HSP activator”).
  • the present invention also covers these compositions separately, that is to say on the one hand a slimming composition and / or prevention of inflammatory processes, comprising at least one sirtuin inhibitor and at least one HSP inhibitor, advantageously intended to be applied during the day, and secondly a slimming composition and / or prevention of inflammatory processes, comprising at least one sirtuin activator and at least one HSP activator, advantageously intended to be applied at night.
  • the present invention also covers the aforementioned compositions, advantageously slimming compositions and / or prevention of inflammatory processes, further comprising at least one slimming agent, in particular an activating agent for lipolysis.
  • the present invention also relates to the abovementioned compositions, advantageously cosmetic slimming compositions and / or prevention of inflammatory processes, further comprising at least one vascular activating agent.
  • the invention also covers the use of a combination of at least one sirtuin modulator and at least one HSP modulator as active ingredients, in a slimming composition or in the prevention of a process.
  • inflammatory comprising at least one slimming agent and at least one vascular activating agent.
  • At least one HSP inhibitor and at least one sirtuin inhibitor are used as active ingredients of a slimming treatment composition or for preventing an inflammatory process, advantageously intended to be applied during the day.
  • At least one HSP activator and at least one sirtuin activator are used as active ingredients of a slimming treatment composition or for preventing an inflammatory process, advantageously intended to be applied at night.
  • sirtuin inhibitor / activator is meant a compound having properties of inhibition / activation (respectively) of at least one protein of the sirtuin family, or a compound mimicking the inhibition / activation (respectively) of at least one protein of the sirtuin family, in particular sirtuin 1 and sirtuin 2, but also sirtuins 3 to 7.
  • a sirtuin modulator may also be an agonist (synonym of activator or an antagonist (synonymous with inhibitor) of the STACs (cell survival triggering compounds).
  • STACs are enzymes that use NAD + to deacetylate proteins. Through an allosteric mechanism, sirtuins 2 will act with STACs and work together to increase cellular defenses against stress. STACs can be triggered by a stress mechanism, in a way completely independent of sirtuins.
  • HSP inhibitor / activator a compound having inhibition / activation properties (respectively) of at least one protein of the family of HSPs, or a compound mimicking the inhibition / activation (respectively) of at least one protein of the HSP family.
  • the HSP inhibitor / enhancer is preferably an inhibitor / enhancer of one of the following HSPs: HSP70, HSP90, HSP100 and HSPsmall.
  • protection / protector of cell integrity all the mechanisms of prevention against inflammatory processes.
  • vascular activating agent an agent that promotes blood circulation, or that promotes vascular vasodilatation, or that promotes an increase in vascular flow in the tissues concerned or mimics the mechanisms of a sports activity.
  • inhibitor / activator it is intended to inhibit, respectively activate, a protein considered, in particular by an inhibition / activation of the expression of the gene of this protein, an inhibition / activation of the translation of the mRNAs of this gene, and / or an inhibition / activation of the activity of the protein.
  • composition a composition intended to be applied during the day, preferably in the morning between 6-11 hours.
  • night composition is meant a composition intended to be applied at night, preferably in the evening between 18-24 hours.
  • sirtuin activator with an activator of an HSP protein according to the invention advantageously makes it possible to obtain the following effects.
  • Stimulating sirtuins creates chemical stress that negates the protective action of the P53 gene.
  • the stimulation of the constituent heat shock proteins (HSPs) proposed in the context of the invention therefore makes it possible to control the risks of overflow related to the hyperactivity of sirtuins which can, depending on the situation, promote or prevent the occurrence of harmful phenomena (cancer).
  • HSPs heat shock proteins
  • sirtuins could trigger increased activity of apoptotic P53 genes (programmed cell death).
  • the concomitant inhibition of HSPs makes it possible to limit the runaway mechanisms of cellular autophagy and its consequences on replicative aging and on metabolic senescence.
  • sirtuin inhibitors will, by the genomic pathway P53, activate the lipolysis dependent on the LHS (Lipase Hormono Sensitive) and slow down the cellular activity while increasing the preservation of the energy capacities of the cell.
  • the P53 gene is a general controller of cell death, but the protection it exerts accelerates aging moderately and does not interfere with cell lifespan.
  • the invention intends to cover the use of at least one sirtuin inhibitor as slimming active ingredient in combination with an HSP inhibitor, especially in the compositions of the present invention in particular intended to be administered in the morning.
  • HSPs inhibitors also makes it easier to empty the adipocytes, by reducing the storage of AG (fatty acids) and to eliminate the risk of memorizing repeated cellular stress.
  • the enzymatic sirtuin activators (Deacetylases Sir2) will mimic the caloric restriction which makes it possible, in the nocturnal phase, to reduce the fat store contained in the adipocytes, and to block the maturation of the pre-adipocytes, in particular when they are associated with at least one HSP activator. It is known that the action of the genes Sirt 1 and Sirt 3 have an action on caloric restriction (inhibition of adipogenesis and activation of adipocyte lipolysis) and thanks to the inhibition of decoupling protein 2 (UCP2), the Sirt 1 positively regulate insulin secretion. Inflammatory processes, through the activation of alpha peroxisomes (PPARs alpha) and Forkhead Fox transcription factors 0 1, 3, 4 (FOXO) will decrease.
  • PPARs alpha alpha peroxisomes
  • FOXO Forkhead Fox transcription factors 0 1, 3, 4
  • the thin woman has cellulite areas that are sometimes more impressive than in a woman overweight. Also it is essential to distinguish a loss of weight (by calorie restriction or by simple loss of water) of a thinning (loss of fat volume). Their mechanisms are complementary and their effects come together in the prevention of inflammatory processes.
  • the increase in vascular flow will trigger the activation of HSPs and that of PPARs thus blocking the proliferation of smooth muscle cells, by repressing the activity of the telomerase enzyme.
  • vasodilator effect of micro-circulation and alpha PPARs have insulin-like activity, mimicking the beneficial effects of sport.
  • omega-3s activate the chain of PPARs that will activate the mitochondria of liver cells, adipose tissue and muscle tissue, the oxidation of fats.
  • PPARs induce apoptosis of macrophages activated in turn by TNF alpha, in tissues with a significant catabolism of fatty acids, including hormone-dependent fatty tissues.
  • the TNFcx factor is triggered when the adipocytes are hypertrophied, especially when there is evidence of obesity.
  • Sirtuin stimulators like STACs, associated with omega-3s will also have an insulin-like effect and will mimic the lipolytic effects of a sports activity.
  • compositions are interdependent on the biological clock and its oscillations. We obtain a potentiation of the "therapeutic” effects if we keep to a chronomodulated scheme.
  • the method of the invention also makes it possible to overcome the technical problem consisting of a cellulo-score scheme in the cellulite indication, or a chrono-modulated scale of application or setting of the compositions to improve their effectiveness, in strict respect of the biological rhythm of the cell, completely autonomous of the neurological central clock (rhythm chronobiology): alternation of activity and rest phase (of 12 hours), concerning all types of cells.
  • compositions may prove to be inconclusive, ineffective or even pernicious to human health, if cell desynchronization should be triggered in the long term, disregarding the time of application or oral intake of the composition. , as when taking an anticancer medicine that could lose efficiency depending on the time of its taking (cell in permanent time difference).
  • a chronobiology scale over 24 hours to indicate the areas of application of the compositions, to obtain a peak optimization of the effectiveness of active ingredients, according to a personalized lifestyle.
  • the compositions according to the present invention make it possible to treat the various types of cellulite; cellulite fat, fibrous, or aqueous.
  • compositions combine collagen manufacturing stimulators (neo-collagen manufacture).
  • the proliferation of collagen fibers contributes to the formation of interstitial tissue fibrosis, triggered by tissue hypoxia.
  • the type of cellulite is never specified, or it is impossible to obtain a good efficiency if one uses the same composition for cellulite fat, fibrous or demateuse.
  • the inflammatory component is not the same. It is also possible to trigger degenerative processes including cancer.
  • a proliferation of collagen fibers is observed in reaction, which does not fit into the desired approach. Poorly controlled stress carries risks: cardiovascular, degenerative diseases and cancers. Thus it is avoided in the present invention to add compounds that stimulate the formation of collagen fibers.
  • the present compositions prevent inflammatory processes by decreasing the negative effects of repeated stress. It is known that aging effects a time shift of the biological clock of the cells. In this context, it is possible to offer real protection and / or repair of anti-inflammatory prevention mechanisms, by recalibrating the activity of the cell in its phases of rest and work. It is recognized that a chronic dephasing of the rhythm of life of the cells, desynchronization of the biological rhythm, causes a progressive sliding ("jet lag") which can induce a loss for the cell of its abilities of synthesis and elimination of its waste. And finally, this can lead to a morphological configuration change of cell membranes with loss of recognition of the external environment, interrupting any mode of communication. Thus, the method of the invention makes it possible to combat this shift in the cellular rhythm and its consequences.
  • compositions according to the present invention make it possible to fight against the inflammatory processes (of which the phenomenon of cellular aging is part).
  • the activation of lipolysis, the size of the adipocytes will allow, independently or in combination with vascular agents, to limit or block the mechanism of glycation.
  • the kit of the invention contains two different compositions.
  • the kit for cosmetic, pharmaceutical, food or veterinary compositions of comprises a first composition containing at least one sirtuin inhibitor and at least one HSP inhibitor, and a second composition comprising at least one sirtuin activator and at least one minus one HSP activator, the two compositions being packaged separately.
  • the first composition intended to be administered by day, or diurnal composition comprises a sirtuin inhibitor, an HSP inhibitor, and optionally a slimming agent and / or a microcirculation activator (also called vascular activator).
  • the sirtuin inhibitor is chosen from tocopherol nicotinate, niacin (also called vitamin B3), sirtinol, cirsimarine, cirsimaritine, capsaicin, any of the sirtuin inhibitors of formulas 1 to 25, 30 and 32-65 cited in US Patent Application No. 2005/0136537 to Sinclair et al., And any combination thereof.
  • niacin will be for example a mushroom extract, such as oyster mushroom.
  • a source of capsaicin will for example be a pepper extract, such as yellow pepper.
  • An extract of black cumin also called nigella also has sirtuin inhibiting properties.
  • the sirtuin inhibitor may also be a plant extract containing one of these compounds.
  • the sirtuin inhibitor is, for example, chosen from extracts of Micotea debilis, in particular those containing cirsimarine and / or cirsimaritine, and the proteins contained in whole grains such as peas, lentils, barley, wheat, or rye, and the aqueous extracts of these cereals.
  • the sirtuin inhibitor may also be Coenzyme Q10 (ubiquinone).
  • the HSP inhibitor is chosen from deguelin, quercetin (also called meletin, sophretin, or pentahydroxyflavone), L-glutamine or a plant extract containing it, myricetin, kaempferol, and coumestrol, and one of their combinations.
  • the HSP inhibitor may also be selected from plant extracts containing an HSP inhibitory molecule such as an extract of Sericea undulea, an extract of red berries containing myricetin, an onion extract source of quercetin, a caper extract from kaempferol, or a source of coumestrol soy
  • the first composition is advantageously free of a compound having sirtuin activating activity or HSP activating activity. This is not the case of compositions which have been described in the prior art, in particular the compositions containing a sirtuin inhibitor and an HSP inhibitor.
  • the second composition intended to be applied at night, or night composition comprises a sirtuin activator, an HSP activator, and optionally a slimming agent and / or a vascular activator (microcirculatory activator).
  • the sirtuin activator is chosen from
  • a polyphenol such as trans-resveratrol or a derivative of resveratrol, such as di-phenyl-resveratrol or dihydroresveratrol,
  • FOXO 3 which is a transcription factor (Forkhead Box subgroup O)
  • xanthohumol or a plant extract containing it, for example a hop extract,
  • phloridzin or a plant extract containing it, for example an apple extract,
  • Fisetin improves the biochemical pathways of neuron storage, powerful antioxidant, fight against neuronal apoptosis. It is part of the separate class STACS, released at the time of picking fruits and / or vegetables (stress of gathering). It would act by an allosteric mechanism, causing an overrepresentation of the siR-2 homologs and blocking the cyclin protein kinases dependent (CDK2 and CDK4). It would further act on telomerases by protecting them from degradation and termino-terminal fusions,
  • the HSP activator is chosen from
  • the verbascoside phenolic agent
  • a plant extract containing it such as a verbena extract or an olive extract
  • D- D-trehalose which can be extracted from brown algae (lamarine) or Ganoderma Lucidum and which acts as a protective glaze of the cell membrane (cyto-protective), antioxidant and antioxidant by blocking glycation; it helps to fight against rancidity in case of addition of polyunsaturated fats with light chains, omega-3,
  • rosavin or a plant extract containing it, such as an extract of rhodiola rosea,
  • arginine or an extract containing it for example a nut extract
  • Rosavin or a plant extract containing it is advantageously combined with L-carnitine to slow down adipogenesis.
  • the second composition is advantageously free of a compound exhibiting sirtuin inhibitory activity or HSP inhibitory activity.
  • Each of the two compositions may further contain at least one slimming agent, preferably a lipolysis activator or adipogenesis inhibitors.
  • slimming agent is meant an agent having properties for inhibiting the storage of fats or for activating the destocking of fats contained in the adipocytes.
  • the slimming agent may be chosen from slimming agents acting on different biological targets, in particular
  • LHS hormone-sensitive lipase
  • beta / 2-adrenergic receptors by stimulating beta / 2-adrenergic receptors, and / or
  • LPL lipoprotein lipase
  • alfa-2-adrenergic receptors by inhibiting LPL (lipoprotein lipase), and / or by inhibiting alfa-2-adrenergic receptors, and / or
  • PPARs peroxisome proliferator activated receptors
  • the slimming agent can be chosen from:
  • polyphenols including epigallocathechin-3-gallate (ECGC) tea or a green tea cathechine,
  • ECGC epigallocathechin-3-gallate
  • composition is advantageously free of caffeine or contains a very small amount.
  • Inhibitors of adipogenesis may be extracts of Garcinia, Baccharis or Hortinia.
  • forskolin is preferably the predominant slimming agent by weight of the mixture.
  • a slimming agent which will be endowed, in addition to its slimming action itself, siruine activating activity or activating activity of HSP, so as not to cancel the effects produced by the sirtuin inhibitor and the HSP inhibitor that the first composition contains.
  • vascular activating agent which will be provided, in addition to its activating action of the blood circulation itself, with a siruin activating activity or with an inhibitory activity of HSP, so that not to cancel the effects produced by the sirtuin inhibitor and the HSP inhibitor that the first composition contains.
  • Each of the two compositions may further contain at least one vascular activator, preferably an activating agent for the microcirculation.
  • compositions of the invention make it possible to take into account the fundamental component which represents the activation of the vascular system as a factor mimicking physical activity, triggering lipomobilization, activator of lipolysis mechanisms (distinction between direct and indirect lipolysis according to the activated or inhibited receptors),
  • the activation of the vascular component will contribute to accelerate the fatty melting, mimicking the beneficial effect of the sport.
  • the microcirculatory activator can for example act by blocking the differentiation of the cells of the stroma W
  • vascular adipocytes causing blockages of glycation phenomena, accelerating lipomobilization, or stimulating peroxisome proliferator-activated receptors (PPARs alpha).
  • PPARs alpha peroxisome proliferator-activated receptors
  • the oxygen enrichment of a product can trigger an overproduction of pro-activators of the inflammation.
  • the oxygen content of a cell at night decreases and is physiologically less than 5%; but if the state of the vascular delivery network is insufficient, in times of stress, levels of reactive oxygen species (ROS) can increase dramatically and cause significant cellular damage.
  • ROS reactive oxygen species
  • Tissue oxygenation will be too weak to repair the damage of hypoxia and will accelerate the accumulation of oxidative derivatives.
  • Hypoxia will result in a blocking of adenosine triphosphate (ATP) production and the appearance of tissue fibrosis.
  • ATP adenosine triphosphate
  • Obesity or overweight is associated with increased circulating levels of adipokines (LPL, Leptin, Adiponectin), cytokines (TNF alpha, IL-beta, IL-6), activators of inflammatory processes and leads to mobilization and the differentiation of certain cells (monocytes, mesenchymal cells) into adipocytes.
  • the stromavascular fraction (FSV) contains a pool of cells capable of differentiating into adipocytes or endothelial cells, the vasodilatation of the micro-circulatory system will help to reduce the risks.
  • vascular system Any activation of the vascular system is assimilated in its effects to those produced by a physical activity which includes voluntary or non-voluntary activities (NEAT, excercise activity thermogenosis) such as prolonged standing, maintaining an attitude, imperceptible movements related to nervousness: "sport-like” effect.
  • NEAT voluntary or non-voluntary activities
  • the activation of the micro-circulation will trigger the activation of Heat Shock Proteins (HSPs) and Peroxyxomes Proliferator-activated Receptors Alpha (PPARs).
  • HSPs Heat Shock Proteins
  • PPARs Peroxyxomes Proliferator-activated Receptors Alpha
  • the micro-circulation enhancing agents have insulin-like activity, mimicking the beneficial action of a sports activity, considered as a positive stress.
  • the vascular activator is chosen from AHAs (Alpha Hydroxy Acid), and isoflavones or a plant extract containing them, such as a cassava extract or a clover extract.
  • AHAs Alpha Hydroxy Acid
  • isoflavones or a plant extract containing them, such as a cassava extract or a clover extract.
  • the activator of the microcirculation can be chosen from an extract of St.
  • John's wort Ginko-biloba extract, Sophora japonica extract, Centilli asiatica extract, Ruscus extract (Ruscus aculeatus), Climbing ivy extract, Agrimony extract, Pilosella extract (Hieracium piloseila) , an extract of sweet clover (Melilotus of icinalis), an extract of beech buds, an extract of horse chestnut, an extract of dermachlorela, rosavin or a plant extract containing it as a plant extract rhodiola rosea, and any of their combinations.
  • a slimming agent that will be endowed, in addition to its slimming action itself, a sirtuin inhibitory activity or an inhibitory activity of HSP, so as not to cancel the effects produced by the sirtuin activator and the HSP activator that the second composition contains.
  • vascular activating agent which will be equipped, in addition to its action of activation of the blood circulation proper, a sirtuin inhibitory activity or an inhibitory activity of HSP, so not to cancel the effects produced by the sirtuin activator and the HSP activator that the second composition contains.
  • Activators of lipolysis and microcirculatory activators will be used at different concentrations in the daytime composition and in the night composition, and those skilled in the art will be able to adapt these concentrations according to the desired results.
  • the day composition contains deguelin, optionally in the form of an extract of Sericea Mundulea, as an inhibitor of HSPs, optionally combined with a ginko-biloba extract and / or a St. John's Wort extract. .
  • composition intended to be administered by day of the invention according to the invention contains, for 100 ml of composition:
  • composition intended to be administered at the preferred night according to the invention contains per 100 ml of composition:
  • At least one activator of lipolysis chosen from:
  • Antioxidants such as whey protein isolates (glutathione), retinol, piperine-associated curcumin, zinc, vitamin B vitamin derivatives other than vitamin B3, vitamin C or an omega-3 fatty acid and any of their combinations may be incorporated into diurnal and nocturnal compositions.
  • Vitamin C can only be used in day preparations only.
  • low glycemic index substances such as stevia, xylitol and beta-stirol will be chosen.
  • Water-soluble or concentrated tannin concentrates may be of interest as oxygen free anti-radicals, heavy metal sensors, sugar oxirreductors, and for the attenuation of rancid taste caused by the addition of fats (Omega-3) in compositions administered orally.
  • compositions according to the process of the present invention act advantageously on the cells, and especially the adipocytes, by limiting the inflammatory processes.
  • compositions of the present invention are cosmetic or pharmaceutical compositions intended for topical application.
  • topical application means to contact the surface of the skin.
  • the topically applied compositions may be advantageously combined with compositions administered orally so as to supplement or enhance the action thereof.
  • compositions may be in the form of a beverage, a food sauce or a nutraceutical composition such as capsules, tablets or a powder for dilution.
  • compositions of the invention are formulated in a form chosen from the group consisting of an aqueous or oily solution, especially in the form of a beverage or syrups; a cream or gel, aqueous or oily; a milk ; an oil; a mask; an emulsion, single or multiple, a microemulsion or nanoemulsion, especially oil-in-water or water-in-oil or multiple; a lotion; a liquid soap; a formulation for a spray; a paste; a dermatological bread; an ointment ; a solid, especially in the form of granule, tablet, powder, ampoule, pencil; or a foam.
  • a cosmetic composition according to the invention preferably contains at least one excipient selected from the group consisting of preservatives, emollients, emulsifiers, surfactants, moisturizers, thickeners, conditioners, mattifying agents, stabilizers, antioxidants , texture agents, gloss agents, film-forming agents, solubilizers, pigments, dyes, perfumes and sunscreens.
  • excipients selected from the group consisting of preservatives, emollients, emulsifiers, surfactants, moisturizers, thickeners, conditioners, mattifying agents, stabilizers, antioxidants , texture agents, gloss agents, film-forming agents, solubilizers, pigments, dyes, perfumes and sunscreens.
  • compositions of the invention may contain, in particular, the following ingredients: purified water, purcellin oil, paraffin, Sepigel 305, vegetable glycerin (hydrating agent), aloe vera, cetyl alcohol, dodecanol (emollient-surfactant), tocopheryl acetate (vitamin E and derivatives), Silicone oil, Retinoic acid (synthesis of dermis fibers), Thyme extract (antiseptic), Chamomile extract (cleanser), Zeaxanthin (natural antioxidant), Hyaluronic acid (to counteract the melting of fats and avoid slackening), Beta sitosterol (lowers cholesterol / anti-inflammatory / anti-cancer).
  • purified water purcellin oil, paraffin, Sepigel 305, vegetable glycerin (hydrating agent), aloe vera, cetyl alcohol, dodecanol (emollient-surfactant), tocopheryl acetate (vitamin E and derivatives), Silicone oil, Retinoic
  • compositions can be colored or not, as their perfume can be incorporated during their manufacture or after, by proposing a perfume kit that will be chosen (a few drops to mix).
  • compositions have the effect of reducing the risk of glycation.
  • Glycation is one of the phenomena, responsible for vascular aging, the appearance of cell damage, which can trigger the release of cytokines.
  • the proliferation of collagen and / or elastin and / or fibrin fibers contributes to the aggravation of tissue hypoxia by compression of the microvessels of the tissue, to the appearance of tissue fibrosis, and promotes the occurrence of cellulite .
  • the active ingredients of the compositions according to the present invention avoid such blooms.
  • the kit of compositions according to the invention makes it possible to fight against cellulite.
  • Cellulite is an inflammatory phenomenon responsible for fatty acid storage of adipocytes, differentiation of FSV cells into adipocytes, tissue fibrosis by glycation and the decrease or disappearance of the micro-circulatory network of tissues or organs. Obesity is characterized by alterations in the metabolic and secretory pathways of adipocytes. It is synonymous with chronic inflammatory phase. Activating lipolysis helps to prevent cellular differentiation of pre-adipocytes into adipocytes and cells of the vascular stroma fraction.
  • lipolysis responds to one of the treatments for inflammation.
  • a typical composition to fight against cellulite fat is emulsion water in oil.
  • a typical composition for combating fibrous cellulite is a gel or cream in the form of an oil-in-water emulsion.
  • a typical composition for combating aqueous cellulitis is a cream in the form of an oil in water.
  • the inflammatory component is not the same according to the stages of adipocyte differentiation. It is divided into three stages: the proliferation of adipoblasts, pre-adipocytes that have acquired sufficient nuclear receptors for adipogenesis (PPARs, RXR), and the storage phase of lipids in the adipocyte. But any forced expression of the nuclear receptors whose PPARs gamma 2 in a fibroblast can induce its differentiation in adipocyte. This explains the importance of defining the inflammatory state of a tissue, such as an area of subcutaneous cellulitis.
  • adipose tissue has a central organ status of metabolism and inflammation, not just a storage status. It is recognized that adipose tissue does not contain only adipocytes, but other cells that explain its endocrine activity.
  • compositions will not be used for adipose, fibrous or edematous cellulitis.
  • the obligation to adapt the dosage of the compositions but by associating a vascular factor that will enhance the direct or indirect tissue lipolysis (blocking beta / alpha 2-adrenergic receptors, A2A receptors for adenosine and adipogenesis by blocking the Peroxyxoma Proliferator-activated Gamma Receptors (PPARs), while decreasing inflammatory phenomena.
  • PPARs Peroxyxoma Proliferator-activated Gamma Receptors
  • sirtuin genes contributes to lipolysis by blocking PPARs that stimulate the transcription of several genes in favor of adipogenesis.
  • Sirtuins by mimicking the caloric restriction, will maintain the respiratory metabolism (blocking the permease UCP 2), thus preserving the production of adenosine triphosphate (ATP).
  • Nicotinamide adenine dinucleotide (NAD) enhances the activity of enzymes in the sirtuin family that affect certain anti-inflammatory processes. Synergism is emphasized between the cells of the tissues involved in the metabolism and the inflammatory cells.
  • composition according to the present invention may be used in the context of a slimming cosmetic care method, such as a slimming treatment method using a machine such as a laser, a radiation device, or a mechanical massage apparatus for the skin .
  • the products of the invention are intended both for women's care and for men's care.
  • the present invention covers a method of care slimming and / or prevention of inflammatory processes (including cosmetic, dermocosmetic, pharmaceutical, veterinary, topical and / or oral care): including application or taking in the morning or at sunrise of a diurnal composition according to the method of the present invention and the application or oral intake in the evening or at bedtime of a night composition according to the present invention.
  • inflammatory processes including cosmetic, dermocosmetic, pharmaceutical, veterinary, topical and / or oral care
  • the subject of the present invention is also the kit of compositions described above for its use in the treatment and / or prevention of inflammatory processes in humans or in animals, such as overweight, obesity, diabetes mellitus and type 2, cardiovascular diseases, cancers, skin aging.
  • compositions comprising inhibitor pairs of sirtuin and HSPs or activators of sirtuin and HSPs, and preferably applied according to the alternation of the nycthemeral cycle, are so-called "attack treatment” compositions, for get maximum efficiency on the cells. This treatment typically lasts 30 days.
  • compositions comprising at least one modulator (inhibitor or activator) of sirtuin combined with at least one modulator (inhibitor or activator) of HSP, optionally in the presence of at least one slimming agent and / or at least one vascular activator agent.
  • the present invention also covers the use of a combination of at least one sirtuin modulator and at least one HSP modulator as active ingredients, in a slimming or preventive composition of the inflammatory processes.
  • the invention also relates to a cosmetic, pharmaceutical, food or veterinary composition
  • a cosmetic, pharmaceutical, food or veterinary composition comprising at least one HSP activator and at least one sirtuin activator as described above.
  • This composition may have all the characteristics described in connection with the 01
  • the invention further relates to the use of such a composition for increasing activity against cellulite and inflammatory processes of a composition containing at least one sirtuin inhibitor and at least one HSP inhibitor.
  • compositions can satisfy the cosmetic directives of the EEC (Annex VI, 76/768 / EEC), in order to obtain the biocosmetology or organic oral products label.
  • Microangioscopy (magnification 400 times); evaluates capillary tortuosity, pericapillary edema and dilation of the venous side.
  • compositions are preferably applied or ingested for at least 30 days twice a day (morning and evening) following a chronomodulated scheme.
  • the present invention particularly covers a method of care comprising the diurnal application of a diurnal composition according to the present invention, and / or the nighttime application of a night composition according to the present invention.
  • the day / night cycle is assessed according to the hours of a day, taking into account the time zone and the sunrise or sunset of the person being treated.
  • the cycle can usually vary from two to three hours depending on people and their lifestyle.
  • Biological rhythms affect cellular metabolisms, major vital functions, nervous system and motor skills. The rhythms of 24 hours are usually synchronized with day-night alternation, activities and rest.
  • the cells have a circadian rhythmic autonomy; they can synchronize their activity, and constitute one or more individualized structures called oscillators (or biological clock).
  • Biological rhythms are genetically determined and modulated by timing factors.
  • the chronotype classifies individuals primarily according to their preference for a more morning (morning types) or late (evening types) sleep schedule, compared to the general population. This preference has been associated with a circadian phase respectively earlier morning or later.
  • the sleep-wake cycle depends on the circadian rhythm of the Central Nervous System (CNS) by the secretion of cortisol: the maximal blood load in glucocorticoids precedes by 2:00 at the end of the night, is very probably the guarantor of a gluconeogenesis of protein origin at the end of the night. awakening moment.
  • CNS Central Nervous System
  • melatonin sep hormone
  • the circadian time structure will resynchronize according to the new time constraints.
  • 8-hour advance (8-hour time difference) by doing physical activity for a duration of more than two hours, the resynchronization is carried out in less than 48 hours whereas the normal duration would have been several days.
  • the alteration of the activity / rest cycle seems to be one of the most relevant markers. This alteration is easily measured using small piezoelectric accelerometers worn on the wrist (in a human being) for at least three days.
  • compositions may be performed according to a shifted socket, according to the external desynchronizations (slider provided).
  • the day composition between 6-9 hours and the night composition between 18 to 21 hours.
  • the daytime composition between 9-11 hours and the nighttime composition between 22-24 hours.
  • the ruler effectively shifts the oral intake or the application, according to a work of night or day.
  • Risk factors for cellular desynchronization will be avoided, among which we can mention alcohol, cola drinks, coffee, tea, beta-blockers, glucocorticoids, nicotine, tobacco, night light , jet lag, lack of physical activity; and chronic stress (night or morning work).
  • tryptophan intake orally, of increase the secretion of N-acetyl-cysteine (NAC), via the manufacture of serotonin.
  • Sources of tryptophan include dried fruits (almonds, walnuts, hazelnuts ...), cruciferous vegetables and legumes (B6, Mg), avocado (B6), magnesium-rich water, fatty fish or oils rich in Omega-3, white meat, dietary supplements containing Mg-Taurine, B6 and Omega-3.
  • the invention also relates to the use of the combination of the diurnal and nocturnal compositions described above to obtain a resynchronization effect of the circadian rhythm of the central nervous system.
  • Quantities are given for illustrative purposes only and are for 100 mL compositions.
  • a dietary composition of 100 mL may contain the following ingredients.
  • glucose oxidative action
  • anti-inflammatory oxidative action
  • curcumin oxidative agent
  • piperine oxidative agent
  • Other compounds may be added for their oxidative action (glutant), anti-inflammatory, or to block the risk of angiogenesis (curcumin or piperine).
  • a 100 mL night composition may contain the following ingredients.
  • Kit comprising a composition Day and a night composition to fight against cellulite fat
  • Each composition has a volume of 100 ml.
  • compositions may be in the form of a water-in-oil or oil-in-water-in-oil emulsion.
  • Example 4 Kit Comprising a Day Composition and a Night Composition for combating Fibrous Cellulitis
  • Each composition has a volume of 100 ml. Each compound is included at a rate of O.Olmg to lg.
  • compositions may be in the form of an oil-in-water or water-in-oil-in-water emulsion.
  • Example S Kit of compositions for combating aqueous cellulitis
  • compositions of Example 3 in which the draining agents and hyaluronic acid are increased in concentration are taken.
  • Glycerol humidity to facilitate penetration
  • extracts of Agrimony, Pilosella and uscus are added to each composition and each of the compositions can be in the form of an oil-in-water or water-in-water emulsion. in-oil-in-water.
  • Powder for the day comprising:
  • the preventive effect of the inflammatory mechanisms will have the expected beneficial effect of improving the general state of health (feeling better, reducing the sensitivity to stress, mild analgesic effect), a more satisfactory general appearance and an improved effect compared with use of sirtuin modulators alone.
  • Each compound is present in an amount of 0.01 mg to 1 g.
  • a moisturizing agent such as a pure aloe vera juice
  • probiotic agent not obligatory (in order to treat functional colopathies or to reinforce the defenses of the digestive mucosa, in the event of no familial contraindication of a digestive cancer);
  • alfalfa protein vegetable protein
  • guarana extract hanginger suppressant effect
  • tryptophan precursor of niacin / activator of the P53 gene
  • policonasol a policonasol (slimming agent due to its action limiting the absorption of fat);
  • trace elements such as NaCl, Mg and / or K.
  • Each compound is present in an amount of 0.01 mg to 1 g.
  • Urucum extract and acerola containing flavonoids; - polyphenols and flavonoids from; dehydrated strawberries (40%), raspberries (20%), blueberries (20%), acai berries (20%);
  • a moisturizing agent such as a pure aloe vera juice
  • probiotic agent not obligatory (in order to treat functional colopathies or to reinforce the defenses of the digestive mucosa, in the event of no familial contraindication of a digestive cancer);
  • alfalfa protein vegetable protein
  • guarana extract hanginger suppressant effect
  • tryptophan precursor of niacin / activator of the P53 gene
  • policonasol a policonasol (slimming agent due to its action limiting the absorption of fat);
  • Each compound is present in an amount of 0.01 mg to 1 g.
  • a moisturizing agent such as a pure aloe vera juice
  • probiotic agent not obligatory (in order to treat functional colopathies or to reinforce the defenses of the digestive mucosa, in the event of no familial contraindication of a digestive cancer);
  • alfalfa protein vegetable protein
  • guarana extract hanginger suppressant effect
  • policonasol a policonasol (slimming agent due to its action limiting the absorption of fat);
  • the clinical tests were carried out on voluntary patients (10 to 20), having no current treatment (no hormonal treatment among others), no declared diseases, no family history of digestive and / or hormonal cancers.
  • kit of the present invention for group number 2 (G2), comprising a first composition based on ingredients chosen for their antagonistic effects of sirtuins and HSPs intended for daily consumption corresponding to the formula below, and a second composition containing sirtuin agonists and HSPs for nocturnal absorption corresponding to the formula below.
  • G2 group number 2
  • the distribution of recruited patients was not randomized but was done in a mode introducing random parameters such as the chronology of recruitment, random consultations, and the allocation of treatment to be administered according to an equal number of people entering in the test.
  • the average age of the volunteers in the trial was 45 years (+/- 5 years).
  • Vegetable consumption in both groups was less than 3 to 5 fruits and vegetables per week, with a variation of (+/- 3), which corresponds to an average consumption in a 45-year-old population (+/- 5 years) below current recommendations.
  • Pineapple extract (lipolytic) Guarana 340 mg
  • Sweet potato extracts 2.5 g
  • composition administered on day 2
  • This formula contains, in addition to sirtuin inhibitors and HSP inhibitors, several herbal extracts. These extracts have different activities that combine to have anti-apoptotic, anti-inflammatory, lipolytic and vasodilatory effects.
  • Micotea debilis extract 1 g
  • Aqueous extract of Oyster mushroom 10 ml
  • Aqueous extract of cassava root 1.5 ml
  • Aqueous extract of celery 75 ml
  • Rhizomes of the Renoue of Japan 9.74 mg (rich in trans-resveratrol, activator of sirtuine)
  • Strawberry powder concentrate 4 g (sirtuin activator)
  • Rhubarb extract piceatannol source 3 g (sirtuin activator)
  • Licorice extract source of isoliquiritigenin 1.5 g (sirtuin activator)
  • Extract of the Prickly Pear Pricklyard 180 ml (HSP Activator)
  • Aqueous extract of the plant rhodiola rosea 150 mg (HSP activator)
  • Ganoderma Lucidum extract (containing trehalose activator of HSP) Aqueous extract of unfermented green tea: 180 mg
  • Extracts of nuts 2 g (rich in arginine and omega-3)
  • the study has allowed by comparative assays of Gl / G2 compositions measurements of the production of oxygen radicals (ROS), reactive oxygen species produced as normal byproducts of cellular metabolism.
  • ROS oxygen radicals
  • the nature of the protein modification can give important information as to the type of oxidant involved in the oxidation process.
  • Assays were performed by various means, such as spectrophotometric, enzyme-linked assay (ELISA) and or two-dimensional electrophoresis followed by immunoassay (Western blot).
  • the nature of the protein modification can give important information as to the type of oxidant involved in the oxidation process.
  • Oxygen Species In general, oxidative stress is defined as the result of an imbalance between pro-oxidant balance and defense systems (antioxidants), with the result that the production of Active Oxygen Species (OOE) is responsible often irreversible damage to the cell.
  • antioxidants pro-oxidant balance and defense systems
  • OOE Active Oxygen Species
  • Glutathione Oxidized Glutathione (GSS) and Reduced (GPSS), Superoxide Dismutase (SOD) Oxygen Radical Antioxidant Capacity (ORAC) and Total Antioxidant Capacity (TAC)
  • the MDA assay represents only a small percentage (1%) of the decomposition process of lipid peroxides, making it an unattractive marker. He was removed from the balance sheet.
  • Vitamin E which has the capacity to infiltrate within the fatty acids of the cell membrane, blocking the spread of lipid peroxidation.
  • Glutathione peroxidase ensures the elimination of peroxidized lipids.
  • the dosage of erythrocyte Glutathione is significant only when the selenium content is less than 60 ⁇ g / L.
  • Homocysteine is an important marker of atherosclerosis. The oxidation of homocysteine has a direct cytotoxic effect on endothelial cells, partly related to the formation of free radicals.
  • Oxidized homocysteine generates EOA, which in turn will oxidize LDL, particularly in the presence of metals such as iron or copper.
  • Vitamin C to dehydroascorbic acid (intermediate radical, ascorbyl) plays a fundamental role in the regeneration of oxidized vitamin E.
  • a vitamin C level below 4 mg / ml is indicative of an increased risk of coronary heart disease.
  • LDL oxidized lipoproteins
  • Albumin has thiol groups.
  • TRxR thioredoxin reductase
  • Thioredoxin-1 is overexpressed in many human tumors, resulting in decreased apoptosis.
  • TRxR is involved in the degradation of lipid peroxides, hydrogen peroxide and in the regeneration of the ascorbyl radical into ascorbic acid. It is a flavoprotein selenocysteine. 3 / Oxidized Proteins / Nitration: Protein Carbonyl Content f PCP;
  • glucose produces large amounts of ROS and glyoxal.
  • the latter binds to the amino group of proteins resulting in the appearance of carboxy-methyl-lysine residues. These protein residues will bind the copper, and initiate a process of lipid peroxidation, resulting in increased production of glyoxal.
  • HbAlC glycosylated hemoglobin
  • SOD Oxygen Radical Absorbance Antioxidant Capacity
  • ORAC Oxygen Radical Absorbance Antioxidant Capacity
  • TEAC Trolox Equivalent Antioxidant Capacity
  • Zinc deficiency ( ⁇ 5 mg / l) will block the activity of HSPs. Overloading can, on the other hand, expose tissue toxicity. It was necessary in the volunteers to correct the deficiencies in order to be able to interpret the ingestion results of the various compositions.
  • Zinc protects thiol groups against iron-catalyzed oxidation by binding to SH functions with greater affinity than iron. It is known that zinc stabilizes copper-zinc superoxide dismutase facilitating its action. 7 / Sirtuine activities:
  • HDAC histone-deacetylase activity
  • the volunteers in group 2 observed a change improving their well-being, on the three criteria retained (sleep, asthenia, and decrease of the abdominal panicle) towards the 9th day (+/- 2 days).
  • Fatty cast calculated in centimeters, showed a standard deviation of (- 2.3 cm) between group 1 and group 2, in favor of the second group.
  • the decline in sirtuin activity is greater in group 1 than in group 2.
  • ferritin homocysteine
  • the agonist-antagonist re-synchronizing compositions are capable of influencing the behavior of the cells in order to prevent the phenomena of aging, fat overload and cerebral psychic state.

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