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WO2019172566A1 - Agent anti-stress, composition d'agent anti-anxiété ou antidépresseur contenant de l'ionone en tant que principe actif - Google Patents

Agent anti-stress, composition d'agent anti-anxiété ou antidépresseur contenant de l'ionone en tant que principe actif Download PDF

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Publication number
WO2019172566A1
WO2019172566A1 PCT/KR2019/002326 KR2019002326W WO2019172566A1 WO 2019172566 A1 WO2019172566 A1 WO 2019172566A1 KR 2019002326 W KR2019002326 W KR 2019002326W WO 2019172566 A1 WO2019172566 A1 WO 2019172566A1
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Prior art keywords
composition
ionone
active ingredient
anxiety
depression
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English (en)
Korean (ko)
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박태선
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Botanicsens
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Botanicsens
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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • 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
    • 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
    • A61K31/12—Ketones
    • 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
    • A61K8/35—Ketones, e.g. benzophenone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/22—Anxiolytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q13/00—Formulations or additives for perfume 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
    • 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
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/322—Foods, ingredients or supplements having a functional effect on health having an effect on the health of the nervous system or on mental function

Definitions

  • the present invention relates to an antistress agent, antidepressant or anti-anxiety composition containing ionone as an active ingredient, and more particularly, the present invention relates to an antistress composition comprising depression or an salt thereof as an active ingredient, depression or anxiety disorder. It is to provide a composition for preventing, improving or treating.
  • Stress is an adaptive response of the body to internal and external stressors or triggers, and medically, it is defined as a harmful stimulus that promotes the secretion of corticosteroids.
  • Stress began to be used in 1936 when Canadian physiologist Dr. H. Selye published Nature's "Stress Theory.”
  • Stimulus that causes stress is classified into physical, psychological, and physiological stimuli.
  • Physical stimulation refers to temperature, ultraviolet rays, etc. that exist in the natural world
  • psychological stimulation refers to mental pain, anger, anxiety, tension
  • physiological stimulation refers to bacteria, viruses, and allergens.
  • repeated symptoms such as depression, anxiety, insomnia, and loss of appetite caused by psychological stimulation cause diseases such as depression, anxiety, and sleep disorder.
  • Depression is a disease that causes deterioration of daily functions by causing various cognitive, mental or physical symptoms due to lowered motivation and depression, and it causes a decline in daily functioning due to deterioration of overall functions such as thought, motivation, motivation, behavior, and sleep. It is difficult and has a high correlation with the prevalence and suicide rate.
  • Anxiety is a mental disorder that usually shows persistent, unrecoverable neurological hypersensitivity, tension, and anxiety over six months, with extreme anxiety in every minor event for no particular reason. Sleep disorders include psychotic symptoms such as self-dissolution, hallucinations, and delusions. Sleep deprivation experiments in rats showed systemic weakness, skin disease, weight loss, increased energy consumption and decreased body temperature. Severe deaths have been reported (Dugovic et al., 1999 High corticosterone levels in prenatally stressed rats predict persistent paradoxical sleep alterations J. Neurosci. 19 (19); 8656-8664).
  • HPA axis hypothalamic-pituitary-adrenal axis
  • the corticotropin releasing factor (CRF) is produced in the hypothalamus of the brain, which binds to the CRF receptor expressed in the pituitary gland and releases adrenocorticotropic hormone (ACTH).
  • ACTH adrenocorticotropic hormone
  • ACTH reaches the adrenal glands through the blood and lymph nodes, promoting the secretion of glucocorticoids such as cortisol, and the glucocorticoids secreted into the blood are delivered to each organ.
  • Cortisol is a stress hormone of steroid hormones that prepares the body to cope with mental stress by straining the muscles and making the sense organs sensitive.
  • the cortisol hormone is continuously secreted due to repetitive mental stress, the blood concentration of the cortisol is kept constant, causing the body to stay in a tense state and disturb sleep. This, in turn, causes mental stress, causing a vicious cycle of depressive symptoms. Loss of cortisol secretion control function by severe mental stress causes excessive cortisol release, leading to brain atrophy and damage throughout the nervous system, resulting in severe depression and suicide.
  • mice overexpressing the CRF gene symptoms of anxiety and depression are increased and navigational behavior is reduced. It has been implicated in emotional disorders and can cause Cushing syndrome, which causes physical changes such as excessive fat accumulation, muscle atrophy, thin skin and hair loss, and raises plasma levels of corticosteroids (ACTH) and cortisol. Known.
  • CRF antagonists Stenzel-poore et al., 1994. This suggests that the behavior caused by CRF overexpression is mediated by CRF and the CRF receptor.
  • CRF receptors belong to the family of G-protein coupled receptors (GPCRs) in the cell membrane, and when the activity is increased by CRF, the activity of adenylyl cyclase (AC) enzymes underneath is increased to increase cAMP concentration. It is known that related bioreactions occur. On the contrary, when the activity of the CRF receptor is inhibited by the antagonist, it is known that the activity of adenylyl cyclase (AC) underneath is reduced, thereby decreasing the cAMP concentration.
  • GPCRs G-protein coupled receptors
  • benzodiazepine strains such as diazepam, lorazepam, clonazepam and alprazolam are mainly used, and imidazopyridine such as zolpidem.
  • Drugs of the imidazopyridine family are also used to treat short-term insomnia due to anxiety.
  • drugs used for anxiety disorders and mental disorders have a direct effect on the GABA receptors of the central nervous system, which inhibits the central nervous system, resulting in excessive sedation and enhanced central inhibitory effects such as depression, muscle relaxation, and hypnosis.
  • drugs that are used for anxiety disorders and mental disorders have a problem that the psychological and physical dependence and the risk of drug abuse is included.
  • ionone is an antagonist of the adrenal cortical stimulating hormone releasing factor receptor (CRF receptoe anatagonist).
  • CRF receptoe anatagonist adrenal cortical stimulating hormone releasing factor receptor
  • It is an object of the present invention to provide an antistress composition comprising ionone or a salt thereof as an active ingredient.
  • Still another object of the present invention is to provide a composition for preventing or improving depression or anxiety disorder comprising ionone or a salt thereof as an active ingredient.
  • Another object of the present invention to provide a pharmaceutical composition for the prevention or treatment of depression or anxiety disorder comprising ionone or a salt thereof as an active ingredient.
  • the present invention is to solve the above problems, and provides an anti-stress composition comprising ionone or a salt thereof as an active ingredient.
  • the composition may relieve stress symptoms by inhibiting the activity of the corticosteroid hormone releasing factor.
  • the composition may relieve stress symptoms by reducing blood corticosterone concentration.
  • the composition can significantly increase the stress relief effect by further comprising jasmon (jasmone) or salts thereof as an active ingredient.
  • the composition may be a nutraceutical composition, cosmetic composition or fragrance composition.
  • the present invention also provides a composition for the prevention or improvement of depression or anxiety disorder comprising ionone (ionone) or a salt thereof as an active ingredient.
  • the composition may prevent or improve depression or anxiety disorder by inhibiting the activity of the adrenal cortical stimulating hormone releasing factor.
  • the composition may prevent or ameliorate depression or anxiety disorder by reducing blood corticosterone concentration.
  • the composition may further increase the effect of preventing or improving depression or anxiety disorder by further comprising jasmone (jasmone) or a salt thereof as an active ingredient.
  • the composition may be a nutraceutical composition, cosmetic composition or fragrance composition.
  • the present invention provides a pharmaceutical composition for the prevention or treatment of depression or anxiety disorder, including ionone (ionone) or a salt thereof as an active ingredient.
  • the composition may further increase the effect of preventing or treating depression or anxiety disorder by further comprising jasmone (jasmone) or salts thereof as an active ingredient.
  • jasmone jasmone
  • the present invention provides a method for preventing or treating stress, depression or anxiety disorder, comprising administering to or administering to a subject a composition comprising ionone or a salt thereof as an active ingredient.
  • the composition may further increase the effect of preventing or treating stress, depression or anxiety disorder by further comprising jasmone (jasmone) or salts thereof as an active ingredient.
  • jasmone jasmone
  • the present invention provides a use for the prevention or treatment of stress, depression or anxiety disorder of a composition comprising ionone or a salt thereof as an active ingredient.
  • the composition may further increase the effect of preventing or treating stress, depression or anxiety disorder by further comprising jasmone (jasmone) or salts thereof as an active ingredient.
  • jasmone jasmone
  • Antistress, antidepressant or anti-anxiety compositions comprising ionone of the present invention as an active ingredient may act as an antagonist that inhibits the activity of the adrenal cortical stimulating hormone releasing factor (CRF) and the concentration of glucocorticoids such as corticosteroids in blood Reducing the symptoms can alleviate the symptoms caused by stress, prevent, ameliorate or treat depression or anxiety disorder. Therefore, the composition of the present invention can be used as antistress, antidepressant or anti-anxiety dietary supplement composition, cosmetic composition, etc., and can be used as an antidepressant, anti-anxiety agent or a wide range of antipsychotics.
  • CRF adrenal cortical stimulating hormone releasing factor
  • Figure 1 shows the concentration of cAMP according to experimental material treatment in HEK293 cells transfected with CRF receptor.
  • the experimental results were measured in three iterations and then expressed as mean and standard error (SEM) .
  • SEM standard error
  • the statistical significance using Student's T-test was used to verify the significance of the CRF and the test materials (CP 154,526, Ionone, or Ionone and Jasmon). Complex) and when treated with CRF alone, were considered significant at p ⁇ 0.05 (mean ⁇ SEM, * p ⁇ 0.05, ** p ⁇ 0.01, *** p ⁇ 0.001 ).
  • Figure 2 confirms the tail suspension test (A), forced swimming test (B) results and plasma corticosterone index change (C) of the mice administered the ion or a combination of ionone and jasmon.
  • ketone compound ionon acts as an antagonist of corticosteroid-stimulating factor (CRF), reduces blood corticosteroid levels, and improves behavioral indicators of stress, depression or anxiety in animal models.
  • CRF corticosteroid-stimulating factor
  • the present invention provides an antistress composition comprising ionone or a salt thereof as an active ingredient.
  • the ionone is Rubus idaeus (Raspberry, Raspberry), Daucus carota subsp. It is a fragrance ingredient mainly contained in Sativus (Carrot, Carrot), Prunus dulcis (Almond, Almond), Menta (Herb, Herb). It is a ketone compound that mainly gives a floral aroma.
  • the structural formula is C 13 H 20 O, The molecular weight is 192.3 g / mol.
  • Ionone includes isomers of alpha-ionone, beta-ionone, and gamma-ionone represented by the following Chemical Formulas 1, 2, and 3, respectively, depending on the molecular structure.
  • Alphaionone is (3E) -4- (2,6,6-trimethylcyclohex-2-en-1-yl) but-3-en-2-one ((3E) -4- (2,6, 6-trimethylcyclohex-2-en-1-yl) but-3-en-2-one), cyclocitrylideneacetone, cycloistrylideneacetone, irisone and jonon are also called.
  • Alphaionone is a pale yellow transparent liquid with melting point of -49 °C and boiling point of 126 ⁇ 128 °C.
  • Ionone is mainly used as a component of shampoos, soaps, cleaning products, body lotions, cosmetics, shower gels, and hair sprays, and is listed as a flavoring agent in the Korean KFDA and US FDA food additive databases, and is mainly used in soft drinks, ice cream, chewing gum, etc. Used.
  • the only report on physiological activity of ionone is that ionon showed strong antimicrobial activity against harmful microorganisms (Findic et al, Synthesis of Terpenoid-Like Bischalcones from ⁇ - and ⁇ -Ionones and Their Biological Activities, Synthetic Communications, 39: 4362-4374, 2009), but no other biological activity has been reported.
  • the ionone of the present invention may include an ionone hydrate, an ionone derivative, and the like within the range having the same efficacy as the ionone, and may also include a solvent compound or stereoisomer thereof.
  • the method for obtaining the ionone is not particularly limited, and may be isolated from the plant containing the ionone, chemically synthesized using a known manufacturing method, or commercially available.
  • the term “cosmetic acceptable salt”, “food acceptable salt”, “pharmaceutically acceptable salt” or “salt thereof” may be an acid addition salt formed by free acid.
  • Acid addition salts can be prepared by conventional methods, for example by dissolving a compound in an excess of aqueous acid solution and precipitating the salt using a water miscible organic solvent such as methanol, ethanol, acetone or acetonitrile.
  • a water miscible organic solvent such as methanol, ethanol, acetone or acetonitrile.
  • equimolar amounts of the compound and acid or alcohol (eg, glycol monomethyl ether) in water can be heated and the mixture can then be evaporated to dryness or the precipitated salts can be suction filtered.
  • an inorganic acid or an organic acid may be used as the free acid.
  • the inorganic acid may be hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, tartaric acid, and the like, which may be used alone or in combination of two or more.
  • Non-limiting examples of the organic acid are methanesulfonic acid, p-toluenesulfonic acid, acetic acid, trifluoroacetic acid, maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, manderic acid, propionic acid (propionic acid).
  • acid citric acid, lactic acid, glycolic acid, glycolic acid, gluconic acid, galacturonic acid, glutamic acid, glutaric acid, glucuronic acid (glucuronic acid), aspartic acid, ascorbic acid, carbonic acid, vanic acid, hydroiodic acid and the like can be used. These may be used alone or in combination of two or more thereof.
  • the ionone may use a base to make a cosmetically or food acceptable metal salt.
  • Alkali metal or alkaline earth metal salts can be obtained, for example, by dissolving the compound in an excess alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the insoluble compounds salt, and then evaporating and drying the filtrate.
  • the metal salt it is particularly preferable to prepare sodium, potassium or calcium salts, but is not limited thereto.
  • Corresponding silver salts can also be obtained by reacting an alkali or alkaline earth metal salt with a suitable silver salt (eg silver nitrate).
  • Salts of the ionone may include all salts of acidic or basic groups which may be present in the compound of the ionon, unless otherwise indicated.
  • the salt of the ionon may include sodium, calcium and potassium salts of the hydroxy group
  • other cosmetically acceptable salts of the amino group include hardbromide, sulfuric acid, hydrogen sulphate, phosphate, hydrogen phosphate, Dihydrogen phosphate, acetate, succinate, citrate, tartrate, lactate, mandelate, methanesulfonate (mesylate) and p-toluenesulfonate (tosylate) salts, and the like. It can be prepared through the method.
  • anti-stress refers to the relaxation of excessive physical reactions due to internal and external stimulation or to the recovery of mental / physical fatigue. Specifically, the term “antistress” refers to relaxation of tension, relaxation of anxiety or improvement of concentration.
  • composition according to the present invention may inhibit the activity of corticotropin releasing factor (CRF).
  • CCF corticotropin releasing factor
  • CRF receptor genes were transfected into HEK293 cells and then treated with CRF material or ionone, and cAMP concentration was measured. As a result, CRF and ionone were treated simultaneously compared to CRF alone. When the concentration of cAMP of the cells was also significantly decreased (-48%), it was found that ionone acts as an antagonist of the CRF receptor (FIG. 1). Anxiety and depression symptoms found in mice overexpressed by the CRF gene have been shown to be alleviated by the administration of CRF antagonists, indicating that the ionon of the present invention is active as an antistress, antidepressant or antianxiety composition.
  • composition according to the present invention can reduce the concentration of corticosterone in the blood.
  • blood corticosterone concentrations were obtained when dietary supplements containing ionone were ingested in blood corticosteroid concentrations and CRF over-expression mice after stress behavioral indicators in mice intraperitoneally administered with ionone.
  • ionone of the present invention has activity as an antistress, antidepressant or anti-anxiety composition.
  • the antistress composition of the present invention may be a health functional food composition, a cosmetic composition or a perfume composition.
  • the term "health functional food” refers to a food prepared and processed in the form of tablets, capsules, powders, granules, liquids and pills using raw materials or ingredients having useful functions for the human body.
  • 'functional' means to obtain a useful effect for health purposes such as nutrient control or physiological action on the structure and function of the human body.
  • the health functional food of the present invention can be prepared by a method commonly used in the art, and the preparation can be prepared by adding raw materials and ingredients commonly added in the art.
  • the formulation of the health functional food can also be prepared without limitation as long as the formulation is recognized as a health functional food.
  • the health functional food composition of the present invention has the advantage that there is no side effect that may occur when taking long-term use of the drug, unlike the general medicine, food, and excellent in portability, intake as an adjuvant to enhance the stress relief effect It is possible.
  • the ionone when used as an additive of the health functional food, it may be added as it is or used with other foods or food ingredients, and may be appropriately used according to a conventional method. have.
  • the mixed amount of the active ingredient can be appropriately determined depending on the purpose of use, such as prevention, health or treatment.
  • Formulations of dietary supplements may be in the form of powders, granules, pills, tablets, capsules, as well as in the form of general foods or beverages.
  • the foodstuff which can add the said substance is a dairy product including meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, ice cream, etc.
  • Various soups, beverages, teas, drinks, alcoholic beverages and vitamin complexes, etc. may include all foods in a conventional sense.
  • the ionone may be added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less based on 100 parts by weight of the raw material in the manufacture of food or beverage.
  • the amount may be below the above range, and the present invention has no problem in terms of safety in terms of using fractions from natural products. The above amount can also be used.
  • the beverage may contain various flavors or natural carbohydrates and the like as an additional component as a general beverage.
  • the above-mentioned natural carbohydrates may be monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose and polysaccharides such as dextrin and cyclodextrin, sugar alcohols such as xylitol, sorbitol and erythritol.
  • the sweetening agent natural sweetening agents such as tautin and stevia extract, synthetic sweetening agents such as saccharin and aspartame, and the like can be used.
  • the ratio of the natural carbohydrate may be about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 mL of the beverage according to the present invention.
  • anti-stress health functional food in addition to the above-mentioned anti-stress health functional food according to the present invention, various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloid thickeners, pH regulators, stabilizers, And preservatives, glycerin, alcohols, carbonating agents used in carbonated beverages.
  • the anti-stress health functional food composition of the present invention may contain a flesh for preparing natural fruit juice, fruit juice beverage and vegetable beverage. These components can be used independently or in combination. The ratio of such additives is not limited, but is generally selected from 0.01 to 0.1 parts by weight relative to 100 parts by weight of the functional food of the present invention.
  • the term "cosmetic composition” is a composition comprising the compound, the formulation may be in any form.
  • formulations include cosmetics prepared using the composition, such as nutrition creams, eye creams, massage creams, creams such as cleansing creams, packs, lotions such as nutrient lotions, essences, soft cosmetics, and nutrient cosmetics.
  • Cosmetics prepared using the composition, such as nutrition creams, eye creams, massage creams, creams such as cleansing creams, packs, lotions such as nutrient lotions, essences, soft cosmetics, and nutrient cosmetics.
  • Powders, foundations, makeup bases, and the like and may be prepared and commercialized in any of these formulations to achieve the object of the present invention, and are not limited to the above examples.
  • the cosmetic composition according to the present invention can be formulated by a conventional cosmetic preparation method.
  • the cosmetics of the present invention include skin lotion, skin softener, skin toner, astringent, lotion, milk lotion, moisturizing lotion, nutrition lotion, massage cream, nutrition cream, moisture cream, hand cream, essence, pack, mask pack, mask sheet It may be one having a formulation selected from the group consisting of, soap, shampoo, cleansing foam, cleansing lotion, cleansing cream, body lotion, body cleanser, emulsion, press powder, loose powder and eye shadow.
  • the cosmetic composition of the present invention may include other additives such as excipients, carriers, etc., in addition to ionone or salts thereof, and it is possible to apply and blend as needed the usual ingredients formulated into general skin cosmetics.
  • the cosmetic composition of the present invention may further include a transdermal penetration enhancer.
  • transdermal penetration enhancer is a composition that allows a desired component to penetrate into the blood vessel cells of the skin at a high absorption rate.
  • phospholipid components, liposome components and the like used in lecithin cosmetics are included, but are not limited to these.
  • oil which can be mainly used as an oil phase component
  • one or more selected from vegetable oil, mineral oil, silicone oil and synthetic oil can be used. More specifically, mineral oil, cyclomethicone, squalane, octyldodecyl myristate, olive oil, Vitis binifera seed oil, macadamia nut oil, glyceryl octanoate, castor oil, ethylhexyl isononanoate, dimethicone Chicon, cyclopentasiloxane, sunflower seed oil and the like can be used.
  • a surfactant may be used conventional surfactants such as nonionic surfactants, anionic surfactants, cationic surfactants, amphoteric surfactants, phospholipids, and the like, specifically, sorbitan sesquinolate, polysorbate 60 , Glyceryl stearate, lipophilic glyceryl stearate, sorbitan oleate, sorbitan stearate, die-cetyl phosphate, sorbitan stearate / sucrosecoate, glyceryl stearate / polyethylene glycol-100 Stearate, ceteareth-6 oleate, arachidyl alcohol / behenyl alcohol / arachidyl glucoside, polypropylene glycol-26-butes-26 / polyethylene glycol-40 hydrogenated castor oil, etc.
  • surfactants may be used conventional surfactants such as nonionic surfactants, anionic surfactants, cationic surfactants, amphoteric
  • alcohols having 12 to 20 carbon atoms such as cetyl alcohol, stearyl alcohol, octyldodecanol, isostearyl alcohol, etc. may be used alone or in combination of one or more thereof.
  • the aqueous phase component may further add 0.001 to 5% by weight of one or more thickeners such as carbomer, xanthan gum, bentonite, magnesium aluminum silicate, cellulose gum, dextrin palmitate and the like to adjust the viscosity or hardness of the aqueous phase.
  • thickeners such as carbomer, xanthan gum, bentonite, magnesium aluminum silicate, cellulose gum, dextrin palmitate and the like to adjust the viscosity or hardness of the aqueous phase.
  • the cosmetic composition of the present invention if necessary, active ingredients such as higher fatty acids, vitamins, sunscreens, antioxidants (butylhydroxyanisole, propyl gallic acid, elixolic acid, tocopheryl acetate, butylated hydroxy) Toluene), preservatives (methylparaben, butylparaben, propylparaben, phenoxyethanol, imidazolidinylurea, chlorphenesin, etc.), colorants, pH adjusters (triethanolamine, citric acid, citric acid, sodium citrate, malic acid, Sodium malic acid, fmaric acid, sodium pramate, succinic acid, sodium succinate, sodium hydroxide, sodium monohydrogen phosphate, etc., moisturizers (glycerine, sorbitol, propylene glycol, butylene glycol, hexylene glycol, diglycerin , Betaine, glycerin-26, methylgluse-20 and the like), lubric acid,
  • the cosmetic composition of the present invention further comprises a substance capable of auxiliaryly providing essential nutrients to the skin, and may preferably contain auxiliary agents including, but not limited to, natural flavors, cosmetic flavors, or herbal medicines. have.
  • the effective amount of ionone or a cosmetically acceptable salt thereof in the cosmetic composition of the present invention is not particularly limited and may be included in 0.0001 to 20% by weight based on the total weight of the composition. Less than 0.0001% by weight of ionone or its salt in the cosmetics may have a small amount of anti-wrinkle effect, and more than 20% by weight of ionone or its salt may exhibit known toxicity.
  • fragment composition of the present invention may be blended into skin-based bases such as perfumes, cosmetics, bathing agents, foods, pharmaceuticals, and the like, and the blending amount may be appropriately selected to achieve a desired effect according to techniques conventional in the art. It can mix.
  • the formulation of the fragrance composition of the present invention is not particularly limited, but may be any one selected from powder, granule, liquid spray, solid and gel type formulations.
  • the fragrance composition includes a cosmetic article including perfume, a soap cleaning article including a bath soap, a room cleaning article including a glass cleaner, a fragrance article including a car air freshener, a bath article containing a herb-type bathing agent, and stationery It can be used to manufacture industrial products including fragrance products, environmental products containing office fragrances or synthetic resin.
  • Perfume composition of the present invention is based on the total weight of the perfume composition, the active ingredient of the ionon, 0.00001% to 10% by weight, preferably 0.00001% to 10% by weight depending on the product form in which the perfume composition of the present invention is specified 1.0 wt%, more preferably 0.00001 wt% to 0.5 wt%.
  • fragrance compositions include soaps, cosmetics, baths, aroma oils, and the like, specifically, body lotions, shampoos, hair rinses, hair conditioners, hair treatments, antiperspirants, skin lotions, skin creams, deodorants , Perfumes (spray or fumigation), lipsticks, lip creams, baths and the like.
  • These products may contain various additives such as blood circulation promoters, anti-inflammatory agents, humectants, astringents, inorganic salts, organic salts, oily ingredients, surfactants, herbal medicines, pigments, perfumes, sulfur, sinter deposits, fungicides and the like.
  • additives such as blood circulation promoters, anti-inflammatory agents, humectants, astringents, inorganic salts, organic salts, oily ingredients, surfactants, herbal medicines, pigments, perfumes, sulfur, sinter deposits, fungicides and the like.
  • the fragrance composition of the present invention will generally be used as a skin external preparation of cosmetic formulations, such as makeup products, skin lotions, skin creams, in which case it may contain components commonly used in these cosmetic formulations.
  • the fragrance composition of the present invention is preferably used incorporating into a bathing agent in that ionone, the active ingredient, has antistress activity.
  • the active ingredient may be included in the range of preferably 0.00001 to 1% by weight, more preferably 0.0001 to 0.1% by weight based on the total weight of the bath.
  • the bath may be added to the bath water at a concentration of 0.015 to 15 ppm.
  • Bathing agent may contain an inorganic salt, an organic acid, an oily component, etc. in addition to the active ingredient of the fragrance composition of this invention.
  • Inorganic salts include sodium chloride, sodium bicarbonate, sodium carbonate, borax, sodium sulfate, sodium sulfide, sodium sesquicarbonate, sodium nitrate, sodium thiosulfate, sodium polyphosphate, sodium phosphate, calcium oxide, magnesium oxide, calcium carbonate, magnesium carbonate, potassium chloride, sulfide Potassium and the like, and these may be used alone or as a mixture of two or more thereof.
  • These inorganic salts may be added to the bath at least 5% by weight, preferably at least 10% by weight based on the total weight of the bath.
  • organic acid examples include succinic acid, fumaric acid, malic acid, tartaric acid, citric acid, benzoic acid, and the like, which may be used alone or in a mixture of two or more thereof. These organic acids can be added to the bath in the range of 0.1 to 50% by weight, based on the total weight of the bath.
  • oily component examples include waxes, hydrocarbons, higher fatty acids, higher alcohols, esters, silicone oils, and the like.
  • the bath may also further contain other ingredients conventionally used in the art.
  • these components include (a) inorganic acids such as boric acid, metasilicic acid, silicic anhydride, (b) medicinal powders such as fennel, ginkgo, ginger, citrus peel, Valerian root, peppermint, ginseng, oats, (c) coal tar dye, Natural pigments identified as harmless to the human body, such as chlorophyll, riboflavin, saffflower, anthraquinone, (d) vitamins such as vitamin A, vitamin C, vitamin D, vitamin E, (e) sulfur, mica powder, clay powder, Ocher powder, rice bran carbide, fungicides, and preservatives.
  • inorganic acids such as boric acid, metasilicic acid, silicic anhydride
  • medicinal powders such as fennel, ginkgo, ginger, citrus peel, Valerian root, peppermint, ginseng, oats
  • coal tar dye Natural pigments identified as harmless to
  • Such bathing agents can be prepared in any form, such as granules, tablets, solutions, powders and the like.
  • the present invention also provides a composition for the prevention or improvement of depression or anxiety disorder comprising ionone (ionone) or a salt thereof as an active ingredient.
  • depression is a type of mental illness characterized primarily by sadness, tastelessness, loss of feelings, numbness (lack of pleasure), grief, agitation or delay, guilt and worthlessness. Serious cases are accompanied by symptoms such as suicide, hallucinations and delusions.
  • anxiety disorder used in the present invention refers to a case in which excessive psychological pain or severe difficulty in realistic adaptation is caused by pathological anxiety. It is a type of mental illness and is associated with various combinations of psychological and physical “anxiety symptoms” that are not attributable to actual risk but appear as an attack (panic disorder) or persistent state (generalized anxiety disorder). Specifically, anxiety disorders include generalized anxiety disorder, phobia (specific phobias, social phobias, agoraphobia), panic disorders, obsessive-compulsive disorders, and post-traumatic stress disorders ( Post-traumatic stress disorder (PTSD).
  • phobia specific phobias, social phobias, agoraphobia
  • panic disorders obsessive-compulsive disorders
  • post-traumatic stress disorder Post-traumatic stress disorder (PTSD).
  • Depression and anxiety disorders are the most common mental dysfunction disorders. Depression is primarily a chronic depressive state, most of which is accompanied by sleep disorders, low self-esteem, shame, and suicidal tendencies. Depression is therefore considered a complex disorder, and the mechanisms associated with its pathogenesis are unclear. Anxiety disorders are often mental illnesses manifested by anxious feelings. The main features of anxiety disorders are continuations such as actuation or anxiety, catatonia and fear combined with syndromes such as autonomic nerves disturbance, muscle rigidity, and exercise disturbance. Tense emotions.
  • composition for preventing or improving the depression or anxiety disorder of the present invention may be a nutraceutical composition, cosmetic composition or perfume composition.
  • the present invention provides a pharmaceutical composition for the prevention or treatment of depression or anxiety disorder, including ionone (ionone) or a salt thereof as an active ingredient.
  • the pharmaceutical composition for preventing or treating depression or anxiety disorder according to the present invention is not particularly limited as long as it contains ionone or a pharmaceutically acceptable salt thereof.
  • the dose of ionone may be included in a concentration of 0.1 ⁇ M to 1000 ⁇ M, but is not limited thereto.
  • the ionone is less than the concentration range, there is a problem that it is difficult to effectively prevent or treat the depressive symptoms, anxiety disorder symptoms or related diseases, and when the ionone exceeds the concentration range, including cytotoxicity There may be toxicity concerns.
  • compositions for the prophylaxis or treatment of depression or anxiety disorders are powder, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, oral formulations, external preparations, suppositories, and sterilization, respectively, according to conventional methods. It may be formulated and used in the form of injectable solutions, and may comprise suitable carriers, excipients or diluents commonly used in the manufacture of pharmaceutical compositions for formulation.
  • the carrier or excipient or diluent may be lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicide, cellulose, methyl cellulose, undetermined. And various compounds or mixtures including vaginal cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil and the like.
  • diluents or excipients such as fillers, weights, binders, wetting agents, disintegrating agents, surfactants.
  • Solid preparations for oral administration may be prepared by mixing at least one excipient such as starch, calcium carbonate, sucrose or lactose, gelatin and the like in the ionone.
  • excipients such as starch, calcium carbonate, sucrose or lactose, gelatin and the like.
  • lubricants such as magnesium stearate and talc may also be used.
  • Oral liquid preparations include suspensions, solvents, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, preservatives, etc., in addition to commonly used simple diluents such as water and liquid paraffin. .
  • Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, suppositories.
  • non-aqueous solvent and suspending agent propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate and the like can be used.
  • base of the suppository witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerol gelatin and the like can be used.
  • Preferred dosages of the pharmaceutical compositions for preventing or treating depression or anxiety disorders according to the present invention vary depending on the patient's condition, weight, degree of disease, drug form, route of administration, and duration, and may be appropriately selected by those skilled in the art. have. However, for the desired effect, it may be administered at 0.0001 to 2,000 mg / kg, preferably at 0.001 to 2,000 mg / kg. Administration may be once a day or may be divided several times. However, the scope of the present invention is not limited by the above dosage.
  • the pharmaceutical composition for preventing or treating depression or anxiety disorder according to the present invention can be administered to mammals such as rats, mice, livestock, humans by various routes. All modes of administration may be administered, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection.
  • the anti-stress composition of the present invention the composition for preventing or improving depression or anxiety disorder, the pharmaceutical composition for preventing or treating depression or anxiety disorder further comprises a jasmine (jasmone) or salts thereof as an active ingredient to alleviate stress Can significantly increase the effectiveness of preventing, improving or treating depression, anxiety or anxiety disorders.
  • a jasmine jasmone
  • jasmine is a compound contained in plants such as jasmine and yarrow, the structural formula is C 11 H 16 O, the molecular weight is 164.248 g / mol.
  • Jasmon may be represented by the following formula (4), also called cis-jasmone (cis-jasmone).
  • Jasmon is listed as a flavoring agent in the Food and Drug Administration (FDA) and Korea Food and Drug Administration (KFDA) food additive databases and is safe as a food additive in the Joint FAO / WHO Expert Committe on Food Additives (JECFA). Approved.
  • Jasmon's physiological and general functions have been reported to help calcium absorption. Jasmon has been reported to increase calcium absorption and calcium content of microsomes when treated with microsomes of skeletal muscle in dogs (Antipenko et al., Journal of Biological Chemistry 272.5, 1997). Jasmon's LD 50 value has been reported to be more than 5,000 mg / kg safe for oral administration to rats (Jenner, et al., Food and Cosmetics Toxicology 2 (1964): 327-343.).
  • Jasmon of the present invention may include a jasmon hydrate, a Jasmon derivative, and the like within the range having the same efficacy as the Jasmon, and may also include a solvent compound or stereoisomer thereof.
  • the method for obtaining the jasmine is not particularly limited, and may be isolated from a plant containing the jasmine, chemically synthesized using a known manufacturing method, or commercially available.
  • HEK293 cells (American Type Culture Collection, Manassas, VA, USA) were prepared in a 10-well plate in 10% FBS (fetal bovine serum; Gibco, BRL, NY, USA), 1% non-essential amino acids (non 37 ° C. using DMEM (Dulbecco's Modified Eagle's Medium; Hyclone, UT, USA) medium containing essential amino acid) and 1% penicillin / streptomycin (Pen / Strep; Gibco, Grand Island, NY) , 5% CO 2 incubator.
  • FBS fetal bovine serum
  • Gibco, BRL, NY fetal bovine serum
  • 1% non-essential amino acids non 37 ° C. using DMEM (Dulbecco's Modified Eagle's Medium; Hyclone, UT, USA) medium containing essential amino acid) and 1% penicillin / streptomycin (Pen / Strep; Gibco, Grand Island, NY) , 5% CO 2 incubator
  • cAMP activity was measured using a commercial kit (Enzo Life Sciences, NY, USA) and performed according to the manufacturer's protocol.
  • the cAMP concentration of HEK293 cells was significantly reduced (-61%) when CRF and known CRF antagonists (CP154,526) were treated with CRF alone.
  • the concentration of cAMP in the cells was also significantly decreased (-48%), compared with only CRF and beta ionone.
  • the reduction was greater (-54%). It was found that beta ionone acts as an antagonist of the CRF receptor and synergistic effect of beta ionone and jasmine together.
  • the beta ionone and jasmon used were purchased from Sigma-Aldrich (Missouri, USA).
  • the experimental animals were kept in a constant space with a temperature of 23 ⁇ 1 °C and a humidity of 50 ⁇ 10% and kept for 12 hours in a light and dark cycle.
  • the animals were freely fed Chow (orient bio) and negative water, except for the negative deprivation conducted before the sucrose preference experiment. .
  • Tail hanging experiments were performed using the method of Steru et al. (1985). After attaching the fixed device about 1 cm to the tail of the experimental mouse, it is suspended 50 cm from the ground, and the immobilization of the experimental animal using a video tracking system (smart v.2.5.21) The time was measured. When the mouse was suspended and completely stopped without any movement, it was considered as a floating state, and after 2 minutes of adaptation time, the behavioral state was measured for 4 minutes. In general, when stress is induced, anxiety increases and depression increases, resulting in less activity.
  • the plasma corticosterone concentration was significantly decreased (-14%) in the beta ionone group (IO) compared to the control group (CON), and beta ionone and jasmon were simultaneously administered (IO).
  • the plasma corticosterone concentration was found to be significantly reduced (-35%).
  • CRF overexpressing mice received 14 pairs of male and female 7-week-old males and females bred for three generations after wearing CRF overexpressing mice (hemizygous) and wild type mice (littermate) from Jackson lab (Bar Harbor, Maine, USA). It was used for the experiment.
  • the diet supplemented with beta ionone had the same composition as ND but contained 0.2% of beta ionone (see Table 1 below).
  • the beta ionone used was purchased from Sigma-Aldrich (Missouri, USA). Experimental animal breeding was carried out in a environment of 12 hours of light and dark cycles with a temperature of 23 ⁇ 1 °C and a humidity of 50 ⁇ 10%.
  • the body weight of the test animals was measured at a regular time once a week, and the dietary intake was measured every day.
  • mice were fasted for 6 hours at the completion of experimental animal breeding, and blood was collected under anesthesia with avertin. Blood collected from the abdominal aorta was centrifuged at 2000 xg for 15 minutes to separate plasma. Corticosterone concentrations were measured using a commonly used EIA kit (Corticosterone EIA kit; Enzo Life Sciences, NY, USA). Basic experimental methods were performed according to the manufacturer's instructions.
  • the plasma corticosterone of CRF overexpressing mice was significantly increased in both males and females compared to WT mice (male, + 284%; female, + 289%).
  • Plasma corticosterone was significantly reduced in CRF overexpressing mice (male, -32%; female, -26%). From this, beta ionone was found to have an effect of improving the concentration of chronically increased plasma corticosterone.
  • the above ingredients were mixed and filled in an airtight cloth to prepare a powder.
  • tablets were prepared by tableting according to a conventional method for producing tablets.
  • the above components are dissolved in purified water according to a conventional preparation method, dissolved in purified water, and then lemon juice is added in an appropriate amount. After adjusting to 100 mL in total, sterilized and filled in a brown bottle to prepare a liquid formulation.
  • Vitamin B6 0.5 mg
  • composition ratio of the above-mentioned vitamin and mineral mixtures is mixed with a component suitable for a health food in a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional health food manufacturing method.
  • the granules may be prepared and used for preparing a health food composition according to a conventional method.
  • the resulting solution is filtered and obtained in a sterilized 2 l container, sealed sterilization and refrigerated and then stored in the present invention Used to prepare healthy beverage compositions.
  • composition ratio is mixed with a component suitable for a favorite beverage in a preferred embodiment, the composition ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.
  • the compounding ratio is mixed with a component suitable for nutritional longevity in a preferred embodiment, the compounding ratio may be arbitrarily modified, and can be prepared according to a conventional manufacturing method in the cosmetic field.
  • the compounding ratio is mixed and formulated in a preferred embodiment with a component suitable for a relatively softening longevity
  • the compounding ratio may be arbitrarily modified, and can be prepared according to the manufacturing method in the general cosmetic field.
  • the compounding ratio is mixed with a component suitable for nourishing cream in a preferred embodiment, the compounding ratio may be arbitrarily modified, and can be prepared according to a conventional manufacturing method in the cosmetic field.
  • the compounding ratio is mixed with a component suitable for a massage cream in a preferred embodiment, the compounding ratio may be arbitrarily modified, and can be prepared according to a manufacturing method in the general cosmetic field.
  • the compounding ratio is mixed with a component suitable for a pack in a preferred embodiment, the compounding ratio may be arbitrarily modified, and can be prepared according to a manufacturing method in the general cosmetic field.
  • the compounding ratio is mixed with a component suitable for a gel in a preferred embodiment, the compounding ratio may be arbitrarily modified, and can be prepared according to a conventional manufacturing method in the cosmetic field.
  • the compounding ratio is a relatively suitable composition for the cosmetic composition in a preferred embodiment, but can be applied to cosmetics of various uses, including other color cosmetics, according to the efficacy that can be applied to a thin coating on the human body, that is, Ointment may be used for manufacturing, and the mixing ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.
  • Vitamin E 0.01 ⁇ 0.1%
  • the feed additive of Preparation Example 7 was used as an active ingredient to prepare a feed having the following composition.

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Abstract

La présente invention concerne un agent anti-stress, une composition d'agent anti-anxiété ou antidépresseur contenant de l'ionone en tant que principe actif. Plus particulièrement, la présente invention concerne une composition anti-stress et une composition pour la prévention, le soulagement ou le traitement de la dépression ou d'un trouble anxieux, les deux contenant, en tant que principe actif, de l'ionone ou un sel associé.
PCT/KR2019/002326 2018-03-05 2019-02-26 Agent anti-stress, composition d'agent anti-anxiété ou antidépresseur contenant de l'ionone en tant que principe actif Ceased WO2019172566A1 (fr)

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Citations (4)

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JP2006036722A (ja) * 2004-07-29 2006-02-09 Lion Corp 睡眠誘導剤
WO2006097759A1 (fr) * 2005-03-18 2006-09-21 Quest International Services B.V. Compositions de parfum
US20070042056A1 (en) * 2003-05-30 2007-02-22 Hitoshi Aoshima Anti-stress agent
JP2007238610A (ja) * 2006-03-01 2007-09-20 Johnson & Johnson Consumer Co Inc 睡眠作用を改善するための方法

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US20070042056A1 (en) * 2003-05-30 2007-02-22 Hitoshi Aoshima Anti-stress agent
JP2006036722A (ja) * 2004-07-29 2006-02-09 Lion Corp 睡眠誘導剤
WO2006097759A1 (fr) * 2005-03-18 2006-09-21 Quest International Services B.V. Compositions de parfum
JP2007238610A (ja) * 2006-03-01 2007-09-20 Johnson & Johnson Consumer Co Inc 睡眠作用を改善するための方法

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